Application research on improving the uniformity of Zhike Taohua Powder based on powder modification technology

Application research on improving the uniformity of Zhike Taohua Powder based on powder modification technology | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Application research on improving the uniformity of Zhike Taohua Powder based on powder modification technology Lile Feng, Yajun Shi, Junbo Zou, Fei Luan, Xiaofei Zhang, Dongyan Guo, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5179870/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Aim To solve the powder defects that are easy to appear in the preparation process of traditional powder. Methods The defects of powder preparation were excavated by referring to the technology of material science and pharmaceutical science. The composite particles were prepared and the surface characteristics of the composite particles were evaluated by SEM and IR. Further evaluation of the overall prescription preparation. Results The factor causing prescription quality defects was peppermint powder. Preparation of 'core-shell' composite particles to improve the prescription problem. Then the composite particles were returned to the whole prescription, and the powder properties of the prepared composite prescription were improved to a certain extent, the content uniformity was significantly improved, and the material basis of the preparation was not changed before and after modification. Conclusion The 'core-shell' composite particles can solve the powder defects in the preparation of traditional powders. Biological sciences/Drug discovery/Pharmaceutics Physical sciences/Materials science Zhike Taohua Powder particle design composite particles pharmaceutical evaluation return to prescription Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 1. Introduction Traditional Chinese medicine powder is an important material basis for solid preparations of traditional Chinese medicine. Powder is one of the oldest traditional dosage forms with powder as the main form. There are a large number of records of powder in the ancient classic medical classics, Treatise on Febrile Diseases, Mingyi Bielu, and Shennong’s Herbal Classic 1 , 2 . In addition, Chinese medicine powder is also an intermediate for the preparation of other dosage forms, which is of great significance for the preparation and development of dosage forms 3 . However, due to the complexity of its physical and chemical properties, and the different properties of the powder composition of traditional Chinese medicine compound, often lead to poor mixing uniformity and other pharmaceutical problems 4 . The characteristics of traditional Chinese medicine powder affect the preparation of mixed molding 5 . Under the guidance of the theory of traditional Chinese medicine, combined with the powder material science and the production and processing methods of Chinese herbal pieces, the introduction of traditional Chinese medicine powder modification technology can solve the problems of poor fluidity and strong hygroscopicity of traditional Chinese medicine powder preparations 6 , 7 . Powder modification technology is to use physical and chemical methods to change the state of the powder itself, and then change the physical and chemical properties, so as to improve the prescription function 8 . The powder modification technology is applied to the solid preparation of traditional Chinese medicine, and the pharmaceutical method is improved from the perspective of powder science. It is of great significance to improve the pharmacodynamic function of traditional Chinese medicine prescription and the secondary application of traditional Chinese medicine products, so that the traditional preparation of traditional Chinese medicine is closer to the modern preparation 9 . Among them, particle coating technology is one of the commonly used methods for powder modification. Shell particles with smaller particle sizes are orderly embedded on the surface of nuclear particles with larger particle sizes through equipment such as ball mills and ultrafine pulverizers. In this process, the particle size ratio of 'shell-core' structure should be reasonably controlled to achieve the purpose of modification 10 . So as to improve the overall powder characterization properties of the prescription, and at the same time, it can achieve the purpose of correcting bad smell and achieving ideal drug release speed 11 . Chen, et al. 12 introduced magnesium stearate, a medicinal excipient, to prepare 'core-shell' composite particles by ultrafine grinding with Taraxacum mongolicum Hand. -Mazz. and Lobaria retigera Trevis. fine powder. It was found that when the amount of magnesium stearate was 2% and the compounding time was 3 min, the prepared composite particles could significantly improve the problems of poor fluidity and uneven composition of powder raw materials. Zhike Taohua Powder (ZTP) is a cough relieving and expectorant agent successfully developed on the basis of the folk prescription 'Taohua Powder' for the treatment of cough 13 . It is composed of Fritillaria cirrhosa D.Don, Moschus berezovskii Flerov, Borneolum Syntheticum , Mentha haplocalyx Briq., Cinnabaris , Pinellia ternate (Thunb.) Breit., Gypsum Fibrosum Preparatum . It has the effects of clearing lung, resolving phlegm, relieving cough, dredging orifices and cooling, and relieving convulsion. Antitussive for pertussis and chronic cough, measles complicated with pneumonia 14 . In the preparation process of ZTP, due to the differences in the source and properties of the raw materials of traditional Chinese medicine compound, the particle size, density and chroma of each medicinal material after crushing are different, which has a great influence on the uniformity of the effective components of the preparation 15 . In the previous study, it was found that the fluidity of mint raw materials was poor, which was easy to cause the uneven content of components in the whole prescription. In this study, from the perspective of Chinese medicine powder modification, combined with the concept of drug-assisted integration, powder modification was carried out on the fine powder of decoction pieces that caused the defects of prescription preparations, in order to solve the problems of mixing and uniformity of ZTP. The research framework is illustrated in Fig. 1 . 2. Material and methods 2.1 Instruments, drugs, and reagents QE-300 high-speed ultrafine pulverizer (Zhejiang Yili Industry & Trade Co., Ltd.); yS3010 spectrophotometer (Shenzhen Sanenshi Technology Co., Ltd.); iUAZ3000 Malvern laser particle size analyzer (Malvern Panaco); vEGA3 scanning electron microscope (Tesco Trading (Shanghai) Co., Ltd.); DSA-100 optical contact angle measuring instrument, (KRUSS, Germany); 769YP-5T multifunctional tableting machine (Shanghai Pressure Reducer Factory Co., Ltd.); bP-121S 100 thousandth of an analytical balance, (Beijing Sedolis Instrument System Co., Ltd.); tENSOR-27 Fourier Transform Infrared Spectrometer (Bruker, Germany); zRS-8LD intelligent dissolution tester, (Tianjin Tianda Tianfa Technology Co., Ltd.); thermo Scientific UltiMate 3000 HPLC, (Thermo Scientific, USA). F. cirrhosa (No.: 20230201), M. berezovskii (No.: 20210506), B. Syntheticum (No.: 20230315), M. haplocalyx (No.: 20230410), Cinnabaris (No.: 20230304), P. ternate (No.: 20230410), Gypsum F. Preparatum (No.: 20230315) were purchased from Shaanxi Xingshengde Pharmaceutical Co., Ltd. Methanol (chromatographic grade, U.S., Fisher), water (China, Wahaha). 2.2 Investigation of powder properties of prescription medicinal materials and extraction of pharmaceutical defects 2.2.1 Sample preparation In this prescription, M. berezovskii is a valuable medicine, and crushing requires more drugs. M. berezovskii is not easy to crush and investigate, so the remaining six kinds are investigated. Six kinds of decoction pieces such as F. cirrhosa were taken and placed in a high-speed pulverizer. After crushing, the crude powder of the decoction pieces of the medicinal materials could pass through the No. 3 sieve. The 200 g crude powder of the decoction pieces was placed in an ultra-fine pulverizer for micro-pulverization (the temperature of the crushing chamber was-5°C, the grinding filling rate of the fine powder was 75%, and the crushing time was 60 min). Samples were taken at intervals, dried and stored for use; at the same time, the preparation of six kinds decoction pieces fine powder (all through the No.5 sieve, and can pass through the No.6 sieve no less than 95% of the powder). 2.2.2 Particle size investigation The particle size of each sample was determined with the help of the dry method of Microtrac laser particle size analyzer (S3500), and the characteristic values of different particle size distributions ( d 10, d 50, d 90) of each sample were recorded, and the regression equations between d90 ( Y ) and pulverization time ( X ) were further established to explore the pulverization pattern of the medicinal tablets. 2.2.3 Determination of fluidity and wettability The angle of repose of each sample was measured by BT-100 powder characteristic analyzer to further evaluate the fluidity of the powder. Put different samples on the sieve net, open the instrument to make the sample fall slowly until the sample presents the highest cone, and use the protractor to measure the angle of repose of the sample near the cone. The contact angle of each sample was measured by K100C automatic surface tension and contact angle tester. Further judge the wettability of the powder. 0.2 g of the sample to be tested was taken, and the sample was prepared into a circular tablet with a diameter of about 10 mm and a hardness greater than 60 N by a multifunctional tabletting machine. The contact angle of each sample was determined by using pure water as the contact medium. 2.2.4 Determination of bulk density of fine powder of medicinal materials The bulk density of fine powder of each medicinal material was investigated and determined by fixed volume. The samples of each medicinal material were sampled according to the FDA's 'Drug Sampling Guidelines', and the samples were slowly dropped from the fixed funnel to form the highest cone at the bottom of the funnel. Samples were taken from the upper, middle, lower, anterior, posterior, left and right seven sites of the cone, respectively. The samples were slowly dropped into a 1.5 mL EP tube through a fixed funnel until the EP tube was filled and the excess samples were scraped. The bulk density of each sample was calculated by the ratio of mass and volume. Each point was sampled three times and the bulk density of the sample was measured in parallel. 2.2.5 Determination of color difference of fine powder of medicinal materials The color difference of the fine powder of the decoction pieces was measured by a spectrophotometer. The methodology of six kinds of medicinal materials was investigated, and their precision, repeatability and stability were investigated. The samples were taken according to the above FDA sampling method, and seven different sites of the fine powder of the six medicinal materials were taken for testing. Seven groups of samples of fine powder of medicinal materials were placed in the sample instrument of spectrophotometer. After calibrating the instrument, the sample pool was installed to start the measurement. The CIE1976 color space was selected, and the color difference of fine powder was judged by calculating the comprehensive chroma value ΔE*ab=[(ΔL*) 2 +(Δa*) 2 +(Δb*) 2 ] 1/2 . Each group was measured 3 times in parallel, and the comprehensive color difference ΔE*ab was calculated. 2.2.6 Investigation on the fluidity of prescription excluding some medicinal materials The fine powder of the medicinal materials with large differences was removed, and the angle of repose of each sample was measured by BT-100 powder characteristic analyzer to further evaluate the key factors affecting the fluidity of the prescription. 2.3 Establishment of modification process 2.3.1 Investigation of shell particle size The fine powder of P. ternate was used as the initial material to be put into the ultrafine pulverizer (temperature-5°C, filling rate 80%, amplitude 5.5 mm) for intermittent sampling. The particle size of the powder in different time periods was measured, and the change rule between the particle size of the powder and the grinding time was investigated. 2.3.2 Investigation of nuclear particle size The fine powder of M. haplocalyx was used as the initial material to be put into the ultrafine pulverizer (temperature-5°C, filling rate 80%, amplitude 5.5 mm) for intermittent sampling. The particle size of the powder in different time periods was measured, and the change rule between the particle size of the powder and the grinding time was investigated. 2.3.3 Investigation of powder properties of composite particles The formation of 'shell-core' composite particles: The prepared shell particle P. ternate and the nuclear particle M. haplocalyx were mixed evenly according to the prescription ratio, and then put into the ultra-fine crusher, and the ultra-fine grinding was obtained at-5°C. According to the results of the regression equation of the crushing time-particle size, the shell particles and the nuclear particle fine powder were compounded in the ultrafine pulverizer at 2, 4, and 6 min according to the above preparation method, and the powder index was characterized. 2.3.4 Investigation of physical properties of composite particles 2.3.4.1 FTIR determination Appropriate amount of KBr was taken and placed in a drying oven for 4 h. Then the sample to be tested and the dried KBr were taken to the agate mortar at a ratio of 1 : 100 for fine mixing and tableting, and the infrared spectrum of the sample was determined. 2.3.4.2 SEM microstructure determination A small amount of sample particles to be tested were placed on the sample holder and gilded at a working current of 10 mA and a working voltage of 4 mV for 20 s. The morphology of the particles was observed by scanning electron microscope. 2.4 Study on the regression of composite particles to the powder properties of the whole party The modified decoction pieces composite particles were returned to the whole prescription, and mixed evenly with the remaining powder of the prescription according to the prescription ratio as ZTP; the original prescription powder of ZTP was prepared according to the preparation method of the original prescription. The particle size, color difference, bulk density, uniformity of active ingredient content and in vitro dissolution of active ingredients of two different powders were investigated respectively, and the effect of powder modification technology was evaluated from the overall level of prescription. The investigation of particle size, fluidity, wettability, bulk density and color difference is consistent with the previous method . In this prescription, F. cirrhosa , P. ternate , and M. haplocalyx are rich in nucleosides. Nucleosides are the basic substances to maintain life activities, and they are also one of the key pharmacodynamic components of commonly used animal medicines. This study intends to determine the content of nucleosides in the prescription to determine the uniformity of the prescription content. 2.4.1 Investigation on the content uniformity of nucleosides 2.4.1.1 Preparation of test solution According to the FDA's 'drug sampling guidelines' sampling method, 7 groups of samples were taken from the original prescription of ZTP and the compound prescription of ZTP.3.0 g of the sample was accurately weighed and placed in a 50 mL conical bottle. 30 mL of purified water was added, weighed, and ultrasonically treated for 60 min. After cooling, the purified water was used to make up for the lost quality. Shake well, transfer the solution to the centrifuge tube, 10000 r/min, centrifuge for 10 min, filter, filter with 0.22 µm microporous membrane, and obtain the test solution. 2.4.1.2 Preparation of reference solution The appropriate amount of uracil, inosine, uridine, adenosine, guanosine, adenine and thymidine was weighed and dissolved with purified water. The mixed reference solution of uracil (11.16 µg/mL), inosine (11.20 µg/mL), uridine (21.56 µg/mL), adenosine (13.54 µg/mL), guanosine (16.18 µg/mL), adenine (36.40 µg/mL) and thymidine (4.55 µg/mL) was prepared by dilution. The mixed reference solution was filtered with 0.22 µm microporous membrane, and the filtrate was taken to obtain the reference solution. 2.4.1.3 Preparation of negative sample solution The medicinal materials containing nucleosides were removed, and 3.0 g was accurately weighed and placed in a 50 mL conical flask, 30 mL of purified water was added, weighed, and ultrasonically treated for 60 min. After cooling, the purified water was used to supplement the lost quality, shaken, and the solution was transferred to a centrifuge tube. 10000 r/min, centrifuged for 10 min, filtered, filtered with a 0.22 µm microporous membrane, and the negative sample solution was obtained. 2.4.1.4 Chromatographic condition Agilent 5 TC-C18 (2) 250×4.6 mm, 5 µm chromatographic column was used. The mobile phase was methanol (A): water (B), gradient elution 0 ~ 5 min, A: 1%~2%; 5 ~ 15 min, A: 2%; 15 ~ 20 min, A: 2%~5%; 20 ~ 30 min, A: 5%~15%; 30 ~ 35 min, A: 15%; 35 ~ 40 min, A: 15% ~20%; 40 ~ 45 min, A: 20%~1%; the flow rate was 0.8 mL/min. The detection wavelength was 260 nm. The injection volume was 20 µL, and the column temperature was 35°C. The time was 45 min 16 , 17 . 2.4.2 Homogeneity of Cinnabaris content According to the FDA's 'Drug Sampling Guidelines' sampling method, 7 groups of samples were taken from the original prescription of ZTP and the compound prescription of ZTP, and the content of cinnabar was determined. About 1.0 g of each sample particle was accurately weighed and placed in a Kjeldahl flask, and 20 mL of sulfuric acid and 3 g of potassium nitrate were added for heating and digestion. After that, 3 g of potassium nitrate was added every 30 min until the solution was nearly colorless. Then the solution was cooled to room temperature and transferred to a conical flask. The flask was washed with 50 mL of distilled water, and the washing solution was incorporated into the conical flask. The 1% potassium permanganate solution was added dropwise to pink, and the 2% ferrous sulfate solution was added dropwise to red until it disappeared. Then 2 mL of ammonium ferric sulfate indicator solution was added, and the solution was titrated with ammonium thiocyanate to orange red. The consumption volume of the titration solution was recorded. Each 1 mL ammonium thiocyanate titration solution (0.1 mol/L) is equivalent to 11.63 mg of mercury sulfide (HgS) 14 , 18 . 2.4.3 Structural stability evaluation In order to evaluate the structural stability of the 'shell-core' coated composite particles, this study simulated the collision and oscillation that the preparation may be subjected to during transportation. A square area of 2 cm 2 in the slide was selected as the experimental area. After the conductive tape was pasted, it was divided into 4×4 small grids. An appropriate amount of the sample to be tested was evenly blown down in the experimental area of the conductive tape. The transparent tape was used to fix the slide. The low frequency (50 Hz), medium frequency (100 Hz) and high frequency (300 Hz) were successively intervened for 60 min by a constant temperature oscillator. The microscopic morphological changes were observed under a scanning electron microscope 19 . 2.4.4 In vitro dissolution determination According to the 2020 edition of the 'Chinese Pharmacopoeia' Volume IV 'General Rule 0931', the dissolution was determined by slurry method. The original prescription of ZTP and the compound prescription of ZTP were accurately weighed 10 g, and a total of 3 parallel groups were taken for standby. The dissolution medium of the dissolution instrument was 900 mL of 0.1 mol/L hydrochloric acid, the working temperature was 37.5°C, the rotation speed was 100 r/min, and the dissolution method was slurry method. Samples were taken at 5, 10, 20, 30, 60, 90, 120, 150, 180, 210, and 240 min, 4 mL each time, and fresh dissolution medium with the same temperature and volume was supplemented. The sample was filtered by 0.22 um microporous membrane, and 20 µL sample was injected for determination, and the dissolution rate was calculated 20 . 2.5 Statistical analysis All date were expressed as the mean ± standard deviation (SD). The results were analyzed by one-way ANOVA test using SPSS 17.0 software, followed by Dunnett’s test. A P value less than 0.05 was considered statistically significant. 3. Results 3.1 Investigation of powder properties of prescription medicinal materials and extraction of pharmaceutical defects 3.1.1 Particle size investigation According to the analysis of Fig. 2 and Table 1 , the particle size of M. haplocalyx , P. ternate , F. cirrhosa , and Cinnabaris showed a trend of 'decrease-balance-increase'. The correlation coefficient between the particle size of each decoction piece and the grinding time was greater than 0.9, which proved that the ultrafine grinding time was closely related to the change of particle size. M. haplocalyx , P. ternate , F. cirrhosa , and Cinnabaris reached the minimum particle size of 55.235, 36.552, 41.058, and 40.045 µm in 23.10, 20.00, 13.50, 9.31 min, respectively. C. camphora and Gypsum F. Preparatum showed a trend of 'increase-balance-decrease', which was mainly attributed to the increase of surface free energy of decoction pieces particles under the action of high-speed collision and shear. In order to further ensure the overall stability, the particles will agglomerate with each other to further reduce the surface free energy, resulting in an increase in the particle size of decoction pieces. In summary, the particle size is closely related to the crushing time. Table 1 Fitting equation of crushing time (t)-particle size ( d 90) of prescription decoction pieces Specimen Regression equation Correlation coefficient r X (min) Y (µm) M. haplocalyx Y = 0.1471 X 2 -6.7952 X + 133.71 0.923 23.10 55.235 C. camphora Y =-0.4271 X 2 + 18.95 X + 199.32 0.948 22.18 409.518 Gypsum F. Preparatum Y =-0.5053 X 2 + 16.77 X + 108.91 0.936 16.60 248.052 P. ternate Y = 0.1708 X 2 -6.8334 X + 104.9 0.932 20.00 36.552 F. cirrhosa Y = 0.364 X 2 -10.169 X + 112.08 0.975 13.50 41.058 Cinnabaris Y = 0.102 X 2 -1.9646 X + 49.505 0.975 9.30 40.045 3.1.2 Determination of fluidity and wettability The angle of repose and contact angle of powder are important indexes to judge the fluidity and wettability of powder. The smaller the angle of repose and contact angle, the better the fluidity and wettability of the powder, and also indirectly affect the preparation and stability of the subsequent preparations. According to the comparison data of angle of repose and contact angle in Table 2 , the angle of repose of M. haplocalyx and C. camphora was large, and the fluidity of the powder was poor, which indirectly affected the overall prescription pharmaceutics evaluation (angle of repose > 45°). In addition, the contact angle of the powder of each prescription is large and the wettability is poor, which leads to the defects of the whole prescription preparation. Table 2 Determination results of angle of repose and contact angle of Zhike Taohua powder mixture and fine powder of each decoction pieces ( x̄ ±s, n = 3) Specimen Angle of repose (°) Contact angle (°) M. haplocalyx 46.33 ± 0.02 66.61 ± 2.88 C. camphora 47.00 ± 0.09 78.56 ± 1.07 Gypsum F. Preparatum 61.67 ± 0.02 59.92 ± 3.37 P. ternate 44.32 ± 0.09 44.77 ± 1.4 F. cirrhosa 33.33 ± 0.05 92.96 ± 1.51 Cinnabaris 41.86 ± 0.28 103.52 ± 0.63 Original prescription 45.42 ± 0.491 53.04 ± 1.518 3.1.3 Determination of bulk density of fine powder of medicinal materials The average bulk density values of the seven sampling points of M. haplocalyx , C. camphora , Gypsum F. Preparatum , P. ternate , F. cirrhosa , and Cinnabaris are shown in Table 3 . Further calculation of the bulk density RSD values of the seven sampling points of the single-flavor decoction pieces fine powder is 7.48%, 5.23%, 0.61%, 0.74%, 0.59%, and 0.21%. The comparison results of the bulk density of the seven sampling points of the six-flavor decoction pieces are shown in Fig. 3 . The bulk density of seven sampling points of M. haplocalyx and C. camphora were quite different. Table 3 Determination results of bulk density of fine powder of medicinal materials ( x̄ ±s, n = 3) Specimen M. haplocalyx (g/cm 3 ) C. camphora (g/cm 3 ) Gypsum F. Preparatum (g/cm 3 ) P. ternate (g/cm 3 ) F. cirrhosa (g/cm 3 ) Cinnabaris (g/cm 3 ) Upper 0.303 ± 0.003 0.269 ± 0.004 0.967 ± 0.005 0.579 ± 0.002 0.752 ± 0.002 3.153 ± 0.005 Middle 0.287 ± 0.003 0.296 ± 0.010 0.973 ± 0.002 0.575 ± 0.002 0.757 ± 0.004 3.158 ± 0.004 Lower 0.297 ± 0.005 0.298 ± 0.010 0.966 ± 0.003 0.570 ± 0.004 0.746 ± 0.004 3.163 ± 0.004 Front 0.278 ± 0.003 0.306 ± 0.006 0.968 ± 0.007 0.575 ± 0.008 0.750 ± 0.009 3.166 ± 0.005 Back 0.342 ± 0.013 0.268 ± 0.023 0.960 ± 0.004 0.580 ± 0.005 0.746 ± 0.003 3.168 ± 0.006 Left 0.277 ± 0.004 0.291 ± 0.006 0.955 ± 0.012 0.568 ± 0.003 0.754 ± 0.002 3.162 ± 0.007 Right 0.293 ± 0.002 0.300 ± 0.005 0.966 ± 0.005 0.572 ± 0.004 0.747 ± 0.003 3.173 ± 0.006 RSD (%) 7.48 5.23 0.61 0.74 0.59 0.21 3.1.4 Determination of color difference of fine powder of medicinal materials The precision, repeatability and stability of six kinds of medicinal powder samples of ZTP were determined. The results are shown in Table 4 . Table 4 Methodological results of color difference of fine powder of medicinal materials Specimen (ΔE*ab) M. haplocalyx RSD (%) C. camphora RSD (%) Gypsum F. Preparatum RSD (%) P. ternate RSD (%) F. cirrhosa RSD (%) Cinnabaris RSD (%) Precision 0.011 0.014 0.004 0.007 0.005 0.174 Repeatability 0.683 0.154 0.013 0.111 0.129 0.017 Stability 0.143 0.018 0.005 0.004 0.017 0.032 The color difference ΔE * dE * of the seven sampling points of the six medicinal materials of ZTP was measured three times, as shown in Table 5 . From Table 5 , the average color difference values of seven sampling points of six medicinal materials, such as M. haplocalyx , C. camphora , Gypsum F. Preparatum , P. ternate , F. cirrhosa , and Cinnabaris were 58.223, 104.628, 101.916, 103.456, 101.917, and 85.688, respectively. The RSD values of color difference of seven sampling points of single decoction pieces fine powder were calculated to be 4.012%, 1.214%, 0.005%, 0.011%, 0.125%, and 0.009%. The comparison results of color difference of seven sampling points of decoction pieces fine powder are shown in Fig. 4 . Table 5 Results of color difference of fine pink of six medicinal materials of ZTP ( x̄ ±s, n = 3) Specimen M. haplocalyx (ΔE*ab) C. camphora (ΔE*ab) Gypsum F. Preparatum (ΔE*ab) P. ternate (ΔE*ab) F. cirrhosa (ΔE*ab) Cinnabaris (ΔE*ab) Upper 61.521 ± 0.004 104.668 ± 0.006 101.929 ± 0.012 103.474 ± 0.002 101.638 ± 0.006 85.701 ± 0.004 Middle 59.242 ± 0.004 102.692 ± 0.006 101.929 ± 0.012 103.462 ± 0.002 101.920 ± 0.012 85.694 ± 0.001 Lower 61.054 ± 0.004 103.790 ± 0.010 101.929 ± 0.012 103.467 ± 0.010 101.947 ± 0.006 85.692 ± 0.005 Front 56.497 ± 0.006 105.222 ± 0.006 101.918 ± 0.006 103.448 ± 0.005 101.952 ± 0.001 85.689 ± 0.002 Back 56.483 ± 0.002 105.225 ± 0.006 101.915 ± 0.006 103.453 ± 0.002 101.975 ± 0.011 85.686 ± 0.002 Left 56.418 ± 0.006 106.683 ± 0.006 101.919 ± 0.006 103.449 ± 0.005 102.003 ± 0.006 85.681 ± 0.004 Right 56.345 ± 0.004 104.130 ± 0.006 101.922 ± 0.010 103.442 ± 0.002 101.999 ± 0.010 85.678 ± 0.004 RSD (%) 4.012 1.214 0.005 0.011 0.125 0.009 By examining the bulk density and color difference of the fine powder of medicinal materials, the uniformity of the powder was measured according to the RSD value of the bulk density and color difference. When the RSD of bulk density and color difference is large, it is proved that the uniformity of the fine powder is poor and the mixing degree is low. According to the above experiments, it was found that M. haplocalyx and C. camphora fine powders had poor uniformity and low mixing degree. Combined with the results of angle of repose and contact angle, it was indicated that the two may lead to uneven mixing of Zhike Taohua powder and poor uniformity of the drug. In order to further determine the key factors affecting the uniformity of ZTP, the fine powder of medicinal materials with poor fluidity was removed, and the angle of repose of the mixed powder was determined to determine the main influencing factors. 3.1.5 Investigation on the fluidity of prescription excluding some medicinal materials According to the above experiments, it is found that M. haplocalyx , C. camphora , and Gypsum F. Preparatum have a large angle of repose and poor powder fluidity, which may lead to poor mixing of prescription drugs. Therefore, M. haplocalyx , C. camphora , and Gypsum F. Preparatum were removed in turn, and the angle of repose of the mixture of the remaining drugs was determined to judge the drug fluidity. The results are shown in Table 6 . M. haplocalyx powder is the key factor affecting the uniformity of ZTP, which is an important reason for the poor fluidity of the prescription and the uneven uniformity of the preparation. In order to further improve the fluidity of the powder and the uniformity of drug mixing, P. ternate with excellent fluidity and small particle size was selected as the shell particles. Through the mechanical particle composite method, the 'core-shell' coated composite particles were prepared with P. ternate as the shell particles and the fine powder of M. haplocalyx pieces as the core particles, in order to improve the fluidity of the whole prescription and improve the uniformity of the preparation of ZTP. Table 6 Removing the angle of repose of three kinds of medicinal powder prescription ( x̄ ±s, n = 3) Specimen Angle of repose (°) Removal M. haplocalyx 42.22 ± 0.05 Removal C. camphora 45.28 ± 0.04 Removal Gypsum F. Preparatum 46.14 ± 0.03 3.2 Establishment of modification process 3.2.1 Investigation of shell particle size The change rule of shell particle crushing time is shown in Fig. 5 . Among them, d 90 is the particle size, and the smaller the d 90 is, the smaller the particle size is. It can be seen from Fig. 5 that with the extension of superfine grinding time, the particle size of P. ternate decreased gradually. Based on the particle size of d 10 and d 50, the superfine grinding time of P. ternate by shell particle method was determined to be 20 min. 3.2.2 Investigation of nuclear particle size The variation of nuclear particle crushing time is shown in Fig. 6 . With the progress of the crushing process, the particle size of M. haplocalyx gradually decreased. Combining the particle size comparison of d 10 and d 50, the M. haplocalyx fine powder can be directly determined as a nuclear particle. 3.2.3 Investigation of powder properties of composite particles The results of material particle fluidity and wettability under different superfine grinding time are shown in Table 7 . The fluidity of the modified composite particle material fine powder was improved compared with the original two-flavor decoction pieces mixed fine powder. The material showed the best fluidity and wettability when ultrafine grinding for 4 min. It can be preliminarily considered that the preparation process of ultrafine grinding for 4 min is better. Subsequently, IR, SEM and other techniques were introduced to investigate the physical properties of the composite particles and observe the microstructure of the materials. Table 7 Investigation results of powder properties of composite particles ( x̄ ±s, n = 3) Specimen Angle of repose (°) Contact angle (°) Composite particle 2 min 43.617 ± 0.355 82.763 ± 1.101 Composite particle 4 min 41.420 ± 0.380 79.090 ± 1.629 Composite particle 6 min 45.190 ± 0.829 84.837 ± 0.280 3.2.4 Investigation of physical properties of composite particles 3.2.4.1 FTIR determination The infrared results are shown in Fig. 7 . P. ternate has one characteristic peak at 3000 − 2500 cm − 1 and three characteristic peaks at 1500 − 500 cm − 1 . Among the composite particles of ultrafine grinding for 2, 4, and 6 min, only the composite particles of 4 min showed the same characteristic peaks at these wavelengths and the peak intensity was high, indicating that the composite particles of ultrafine grinding for 4 min were well coated. 3.2.4.2 SEM microstructure determination The SEM results are shown in Fig. 8 . The shape of the particles of P. ternate is mostly spherical, and the particles of M. haplocalyx are irregular flakes. The microscopic characteristics of the particles of P. ternate and M. haplocalyx can be clearly observed in the electron microscope of the physical mixture diagram, and no new structure is found, indicating that there is only a simple mixing relationship between the two kinds of medicinal particles in the physical mixture. In Fig. 8 , the B, C and D composite particles show a microscopic morphology completely different from the physical mixture. The composite particles are mostly agglomerates with a rough surface and a compact structure. The composite particles of 4 min can be observed. The spherical particles are coated on the periphery of the irregular sheet structure to form a agglomerated particle with a rough surface and a compact structure. The composite 2 min particles are larger and the coating structure is less compact, and the composite 6 min particles show a partially coated state. It shows that the particle design technology changes the microstructure of M. haplocalyx , and the prepared composite particles form a new microstructure. Based on the results of infrared measurement and scanning electron microscopy, it was determined that the composite particles crushed for 4 min had a better 'core-shell' coating model. 3.3 Study on the regression of composite particles to the powder properties of the whole party 3.3.1 Particle size investigation The particle size of the original prescription of ZTP and the compound prescription of ZTP were determined. The results are shown in Table 8 . After adding ultrafine composite particles, the particle size of the composite prescription decreased significantly. Table 8 Comparison of particle size distribution ( x̄ ±s, n = 3) Specimen d 10(µm) d 50(µm) d 90(µm) Original prescription 23.503 ± 2.946 158.500 ± 6.646 238.733 ± 5.532 Compound prescription 14.490 ± 0.714 142.267 ± 1.665 225.700 ± 0.755 3.3.2 Investigation of fluidity and wettability The angle of repose and contact angle of the original prescription of ZTP and the compound prescription of ZTP were measured, as shown in Table 9 . The fluidity and wettability of the compound prescription of ZTP were improved to a certain extent, and the compound prescription of ZTP could better improve the deficiency of the original prescription. Table 9 Comparison of angle of repose and contact angle distribution ( x̄ ±s, n = 3) Specimen Angle of repose (°) Contact angle (°) Original prescription 45.423 ± 0.491 53.043 ± 1.518 Compound prescription 42.173 ± 0.365 44.833 ± 0.917 3.3.3 Investigation of bulk density and color difference uniformity The results of bulk density are shown in Table 10 . The bulk density of the compound prescription of ZTP increased, which may be due to the smaller particle size of the compound prescription of ZTP, and it was found that the density of the 7 sampling points of the compound prescription of ZTP fluctuated less (RSD = 0.664%), indicating that the mixing uniformity between the particles of ZTP was significantly improved. The color difference results are shown in Table 11 . The color difference ΔE*ab can be used to investigate the mixing uniformity of the two samples. The greater the color difference fluctuation of the sample, the worse the mixing uniformity. The color difference of the samples at 7 sampling points of the compound prescription of ZTP fluctuated slightly (RSD = 0.134%), which once again proved that the particles of the compound prescription were well mixed. The results of comprehensive bulk density and color difference showed that the uniformity of the compound prescription of ZTP was significantly improved. Table 10 Results of bulk density measurement ( x̄ ±s, n = 3) Specimen Compound prescription (g/cm 3 ) Original prescription (g/cm 3 ) Upper 0.750 ± 0.035 0.637 ± 0.007 Middle 0.747 ± 0.006 0.647 ± 0.007 Lower 0.750 ± 0.001 0.637 ± 0.007 Front 0.719 ± 0.003 0.634 ± 0.007 Back 0.714 ± 0.004 0.637 ± 0.006 Left 0.791 ± 0.004 0.637 ± 0.006 Right 0.752 ± 0.006 0.635 ± 0.012 RSD (%) 0.664 3.418 Table 11 Results of color difference measurement ( x̄ ±s, n = 3) Specimen Compound prescription (ΔE*ab) Original prescription (ΔE*ab) Upper 81.898 ± 0.009 78.866 ± 0.006 Middle 81.965 ± 0.002 81.337 ± 0.005 Lower 82.073 ± 0.001 78.742 ± 0.001 Front 82.098 ± 0.016 78.767 ± 0.001 Back 82.141 ± 0.001 78.844 ± 0.005 Left 82.161 ± 0.001 76.392 ± 0.005 Right 82.206 ± 0.010 77.440 ± 0.001 RSD (%) 0.134 1.935 3.3.4 Investigation on the content uniformity of nucleosides 3.3.4.1 Investigation of Exclusiveness The test sample, mixed reference solution and negative sample solution were injected respectively according to the chromatographic conditions. The results are shown in Fig. 9 The negative solution had no interference. 3.3.4.2 Drawing of standard curve The standard curve was drawn with the content of each reference substance (µg) as the abscissa and the peak area as the ordinate. The regression equation was obtained, and the linear relationship was good. The results are shown in Table 12 . Table 12 Linear investigation of seven chemical constituents Specimen linear equation r Range of linearity/µg Uracil y = 129.78x-0.061 0.9999 0.01116 ~ 0.1674 Inosine y = 34.275x + 0.0064 0.9997 0.0112 ~ 0.168 Uridine y = 53.259x-0.0433 0.9999 0.02156 ~ 0.3234 Adenosine y = 85.563x-0.7031 0.9912 0.01154 ~ 0.1731 Guanosine y = 49.38x + 0.0128 0.9998 0.01618 ~ 0.2427 Adenine y = 84.611x-0.0951 0.9998 0.0364 ~ 0.546 Thymidine y = 46.252x-0.0017 0.9997 0.00455 ~ 0.06825 3.3.4.3 Precision, repeatability, stability and recovery rate were investigated Under the above chromatographic conditions, 10 µL of the mixed solution of the reference substance was accurately absorbed, and the sample was injected repeatedly for 6 times, and the peak area was recorded. The RSD of the calculated peak area was less than 3%, indicating that the precision was good. The same batch of samples of ZTP were divided into 6 parts of the same quality. The sample solution was prepared according to the preparation method of the test solution, and the peak area was determined according to the required verification method. The RSD of the peak area was less than 3%, indicating that the repeatability was good. The sample of Tianzhike Taohua Powder was taken and the test solution was prepared according to the preparation method of the test sample. The peak area was determined by chromatographic method at 0, 2, 4, 6, 8, 10, 12, and 24 h. The RSD of the peak area was calculated to be less than 3%, indicating that the sample had good stability at room temperature. Six portions of the same batch of samples with known content were taken, each of which was about 1.5 g. They were accurately weighed and placed in a conical flask with a stopper. An appropriate amount of each reference solution was accurately added to each portion, and purified water was precisely added to 30 mL. The samples were prepared according to the test method. According to the above method, the recovery rate was calculated to be between 95% and 105%, indicating that the method was accurate and stable. 3.3.4.4 Investigation of sample content uniformity Nucleoside content homogeneity is shown in Fig. 10 . The contents of effective chemical components in 7 groups of samples in the original prescription of ZTP were quite different. The RSD of uracil, uridine, adenine, inosine, guanosine, thymidine and adenosine were 20.59%, 21.30%, 22.12%, 22.10%, 20.12%, 24.96% and 14.18%, respectively. The contents of effective chemical components in the compound prescription of ZTP were relatively close. The RSD of uracil, uridine, adenine, inosine, guanosine, thymidine and adenosine were 5.14%, 4.13%, 6.18%, 13.32%, 5.12%, 8.38% and 9.82%, respectively. It was found that the content of the original prescription was relatively low, which may be attributed to the uneven mixing of the original prescription powder, which further led to the low content of each determined component. 3.3.5 Homogeneity of Cinnabaris content The content uniformity of HgS in the particles of the two samples was evaluated by titration method. The results are shown in Table 13 . The RSD value of the physical mixture is 5.394%, the content distribution is discrete and the uniformity is poor. The content difference and RSD values of the composite particles are small, which are 1.115%, respectively. The dispersion of the content distribution is small and the uniformity is better than that of the physical mixture. Table 13 Investigation on uniformity of Cinnabaris content Specimen Sampling volume (g) Volume consumption (mL) HgS measured amount (mg) RSD (%) Original prescription 1.00094 ± 0.001 3.550 ± 0.191 41.287 ± 2.227 5.394 Compound prescription 1.00190 ± 0.001 3.529 ± 0.039 41.037 ± 0.458 1.115 3.3.6 Structural stability evaluation After low-frequency intervention, there is no significant change in the surface morphology of the composite particles. However, the vibration generated during the transportation of preparations in daily life is usually low-frequency oscillation, that is, the 'shell-core' coating structure of the composite particles meets the stability of the daily environment. When the intervention frequency was enhanced, it was found that some fine particles on the surface of the composite particles fell off, indicating that the ' shell-core ' coating structure between the composite particles was a soft coating relying on the molecular force between the particles, and did not change its material basis. The results are shown in Fig. 11 . 3.3.7 In vitro dissolution determination With the increase of dissolution time, the dissolution behavior of the seven components in the original prescription of ZTP and the compound prescription of ZTP was basically the same. The dissolution was rapid in 0 ~ 30 min, and then after a period of platform period, the dissolution rate increased slightly near the end of dissolution time. The dissolution behavior of the original prescription of ZTP and the compound prescription of ZTP is basically the same, and the composite particles basically do not change the dissolution of the drug. The results are shown in Fig. 12 . 4 Conclusion and Discussion The traditional powder of traditional Chinese medicine adopts the preparation process of 'crushing-screening-mixing-sub-dose'. Since the compound powder is used as medicine, and the sources of medicinal materials in the prescription are different, it is very likely to lead to the appearance of pharmaceutical defects such as oral compliance and mixing uniformity, thus affecting the quality and stability of the preparation 9 . In this paper, the M. haplocalyx and P. ternate in the compound were taken as the research objects, and the particle design technology was introduced to study the preparation process of the M. haplocalyx - P. ternate composite particles, and the powder characteristics of the composite particles were characterized. The new idea of applying particle design technology to traditional Chinese medicine powder not only inherits the traditional form of drug delivery, but also solves the common problems that are easy to appear in traditional Chinese medicine powder, that is, particle design technology is suitable for the preparation process of contemporary powder and other solid preparation intermediates of traditional Chinese medicine 21 . At the same time, based on the idea of quality comes from design', this study draws on particle design technology, combines the powder characteristics of ZTP, and changes the microstructure and macroscopic properties of ZTP without adding foreign substances through mechanical composite process. To a certain extent, it has improved the preparation defects such as poor taste, unstable properties and poor uniformity in ZTP compound, and preliminarily explored the feasibility of particle design technology in the application of solid preparations of traditional Chinese medicine. It provides reference value for the upgrading of traditional Chinese medicine solid preparation products and the reform of technology. At the same time, it provides new ideas and new methods for the optimization of dosage forms of traditional Chinese medicine preparations rich in volatile oils and extremely unstable properties 22 . Declarations Declaration of Competing Interest The authors declared that they have no conflicts of interest. Author Contribution Lile Feng and Mei Wang, Conceptualization, Methodology, Software, and Writing-Original Draft; Yajun Shi, Junbo Zou, and Fei Luan, Data Curation; Xiaofei Zhang and Dongyan Guo, Visualization, Investigation; Bingtao Zhai, Software, Validation; Mei Wang, Writing-Review & Editing; All the authors listed have read and approved the final manuscript. Acknowledgments This work was financially supported by the National Natural Science Foundation of China (No. 82274105), the Project of Shaanxi Provincial Department of Science and Technology (No. 2023-YBSF-474), and Science and Technology Innovative Talent Program of Shaanxi University of Chinese Medicine (No. 2024-CXTD-03) Data Availability The datasets generated and/or analysed during the current study are not publicly available due to Involving business data but are available from the corresponding author on reasonable request. References Zou, J. et al. 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Differential analysis of 7 main nucleoside components in Pinellia ternata and its processed products. Chin. J. Hosp. Pharm. 43 , 1232–1238. 10.13286/j.1001-5213.2023.11.09 (2023). Zhou, X. et al. Application of design technology for preparing Lingzhu Powder particles based on solvent evaporation method. China J. Chin. Mater. Med. 46 , 6028–6034. 10.19540/j.cnki.cjcmm.20211015.303 (2021). Yang, Y. et al. Innovation of pulvis modification technology in traditional Chinesemedicine preparations: A case study of Shenling Baizhu Pulvis. Chin. Tradit Herb. Drugs . 51 , 3884–3893. 10.7501/j.issn.0253-2670.2020.15.007 (2020). Mei, W. et al. Particle design for improving content uniformity of Hewei Jiangni Capsules. China J. Chin. Mater. Med. 46 , 6045–6052. 10.19540/j.cnki.cjcmm.20211015.301 (2021). Xiang, L. & Miao, M. Modern Research and consideration on traditional Chinese medicine powder. Lishizhen Med. Mater. Med. Res. 30 , 2720–2723. 10.3969/j.issn.1008-0805.2019.11.056 (2019). Jia, X. & Kang, Y. The Relationship between Inheritance and Innovation Should Be WelHandled in the Development of Modernization of Traditional Chinese Medicine. Modernization Traditional Chin. Med. Materia Medica-World Sci. Technol. 21 , 6–11 (2019). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5179870","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":379198112,"identity":"cbd31b14-57c6-4635-80fb-5103dbd1c8c6","order_by":0,"name":"Lile Feng","email":"","orcid":"","institution":"Shaanxi University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lile","middleName":"","lastName":"Feng","suffix":""},{"id":379198113,"identity":"ee875ceb-d233-445d-b449-e1083ba91cf4","order_by":1,"name":"Yajun Shi","email":"","orcid":"","institution":"Shaanxi University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yajun","middleName":"","lastName":"Shi","suffix":""},{"id":379198114,"identity":"6affeb43-102c-46be-a639-0c96906eab5a","order_by":2,"name":"Junbo Zou","email":"","orcid":"","institution":"Shaanxi University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Junbo","middleName":"","lastName":"Zou","suffix":""},{"id":379198115,"identity":"9ffc55f5-fd32-479c-b250-9c1243ef5936","order_by":3,"name":"Fei Luan","email":"","orcid":"","institution":"Shaanxi University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Luan","suffix":""},{"id":379198116,"identity":"44f8a180-0522-489b-825b-30f1009921d2","order_by":4,"name":"Xiaofei Zhang","email":"","orcid":"","institution":"Shaanxi University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiaofei","middleName":"","lastName":"Zhang","suffix":""},{"id":379198119,"identity":"86cd4adb-d0dd-4941-9f26-e483dbe15c8f","order_by":5,"name":"Dongyan Guo","email":"","orcid":"","institution":"Shaanxi University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Dongyan","middleName":"","lastName":"Guo","suffix":""},{"id":379198120,"identity":"66bf8652-dbcd-414c-bad8-41804412f7b0","order_by":6,"name":"Bingtao Zhai","email":"","orcid":"","institution":"Shaanxi University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Bingtao","middleName":"","lastName":"Zhai","suffix":""},{"id":379198121,"identity":"ca155949-6499-4d76-834e-42d7e8af2d3e","order_by":7,"name":"Mei Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIie3PMYvCMBjG8UCgtwRcX+HoZwgEwoGDX6WhkCk9HDsU8VDioOLqx3C88USoyyu3ZlTcxEFxcRJ1c2ozCua3BZ4/LyEkCF4XsPaSLjZJXvgnMVnZlG+w9D8jCKJsbge0fspX6+Xe5V/qZ6Z1rnoRaQxHSXWC37plEFQf0tKp308CuJ5XJvLPSJFZUBa0dgojwiGrSf4P9+QKagxGdpSlHokzYpf1QABDSbyStjtIakqI+YdNIcGS1f6lOTXibIou45QuTpe8iBvDSXVyF8Hzi9XNH+jRZxUEQfDGbhuLS5CRme7jAAAAAElFTkSuQmCC","orcid":"","institution":"Shaanxi University of Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Mei","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-09-30 10:08:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5179870/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5179870/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70547432,"identity":"bc053792-7843-4483-ac73-3c3916b163f0","added_by":"auto","created_at":"2024-12-04 09:37:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":493826,"visible":true,"origin":"","legend":"\u003cp\u003eResearch ideas to improve the homogeneity of the prescription of peach blossom powder for cough relief\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/58544c8bc782cbd4b9d1a8dc.png"},{"id":70548952,"identity":"ff4e08ae-0f00-4f70-a916-083d77836c43","added_by":"auto","created_at":"2024-12-04 09:45:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":210539,"visible":true,"origin":"","legend":"\u003cp\u003eTime-particle size change rule diagram of prescription decoction pieces (BH: \u003cem\u003eM. haplocalyx\u003c/em\u003e；BP: \u003cem\u003eC. camphora\u003c/em\u003e；DSG: \u003cem\u003eGypsum F. Preparatum\u003c/em\u003e；FBX: \u003cem\u003eP. ternate\u003c/em\u003e；CBM: \u003cem\u003eF. cirrhosa\u003c/em\u003e；ZS: \u003cem\u003eCinnabaris\u003c/em\u003e)\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/2e886d96870f4523e5968327.png"},{"id":70549614,"identity":"17bf1a12-441e-4aec-a95a-fa48ff3ab940","added_by":"auto","created_at":"2024-12-04 09:53:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":93441,"visible":true,"origin":"","legend":"\u003cp\u003eComparison chart of bulk density of seven sampling points of fine powder of medicinal materials\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/731af7a995a9a86a880daa13.png"},{"id":70547436,"identity":"5b1f44c0-af5d-4510-8a6a-873ef8f30d08","added_by":"auto","created_at":"2024-12-04 09:37:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":90606,"visible":true,"origin":"","legend":"\u003cp\u003eComparison chart of color difference of seven sampling points of fine powder of medicinal materials\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/eaf86f5e1bf4351e5f6cebcc.png"},{"id":70547427,"identity":"ec7827a4-0ac6-48c6-9f4e-2594767babb8","added_by":"auto","created_at":"2024-12-04 09:37:42","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":177531,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between superfine grinding time and particle size of shell particles\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/2b6d4fd04f8ac236afa9ebc4.png"},{"id":70547429,"identity":"10b3def8-cf5b-4332-b98b-7a6f63e352bd","added_by":"auto","created_at":"2024-12-04 09:37:42","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":174229,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between ultrafine grinding time and particle size of core particles\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/8f9e171aaab6a42475d1d40a.png"},{"id":70547435,"identity":"50518883-a8ba-4bf4-b2c1-a6c9cf5adea4","added_by":"auto","created_at":"2024-12-04 09:37:42","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":239914,"visible":true,"origin":"","legend":"\u003cp\u003eInfrared spectra of each particle (A: \u003cem\u003eM. haplocalyx\u003c/em\u003e; B: \u003cem\u003eP. ternate\u003c/em\u003e; C: Composite particle 2 min; D: Composite particle 4 min; E: Composite particle 6 min; F: Physical mixture)\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/56a71a45cb688ea1d047b347.png"},{"id":70548953,"identity":"a9946533-82f3-4874-8119-424146c6fe30","added_by":"auto","created_at":"2024-12-04 09:45:42","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":319486,"visible":true,"origin":"","legend":"\u003cp\u003eThe microscopic morphology of each sample particle (A: \u003cem\u003eP. ternate\u003c/em\u003e; B:\u003cem\u003e M. haplocalyx\u003c/em\u003e; C: Composite particle 2 min; D: Composite particle 4 min; E: Composite particle 6 min; F: Physical mixture)\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/d8f82659db8615f61e7ee105.png"},{"id":70547438,"identity":"eec41185-3d2f-4646-92ab-016fe8657535","added_by":"auto","created_at":"2024-12-04 09:37:43","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":113108,"visible":true,"origin":"","legend":"\u003cp\u003eSpecificity study (A, test solution; B: mixed reference solution; C: negative sample solution; 1-7: uracil, uridine, adenine, inosine, guanosine, thymidine, adenosine)\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/8a75e8d8e0d934d6adf17c98.png"},{"id":70548955,"identity":"57dcf55b-677c-43df-90d6-45095741e6c3","added_by":"auto","created_at":"2024-12-04 09:45:42","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":168273,"visible":true,"origin":"","legend":"\u003cp\u003eContent uniformity of nucleosides\u003c/p\u003e","description":"","filename":"floatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/8f34e88ab1a30c2eddf04ed3.png"},{"id":70548957,"identity":"f3419f49-2d80-48ef-976e-92b866c62690","added_by":"auto","created_at":"2024-12-04 09:45:42","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":262244,"visible":true,"origin":"","legend":"\u003cp\u003eSEM image of composite particle prescription stability (A-D is the SEM scanning state of composite particles after zero frequency, low frequency, medium frequency and high frequency intervention under 1000 times lens; E-H is the particle state of composite particles at zero frequency, low frequency, medium frequency and high frequency).\u003c/p\u003e","description":"","filename":"floatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/25b815a5a31f96dad2de12d5.png"},{"id":70549618,"identity":"9a22ba26-7c8f-4408-9b37-8d29ae4730e8","added_by":"auto","created_at":"2024-12-04 09:53:43","extension":"png","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":168483,"visible":true,"origin":"","legend":"\u003cp\u003eIn vitro dissolution investigation\u003c/p\u003e","description":"","filename":"floatimage12.png","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/b2e15b3f9e372c6ad62916f0.png"},{"id":70550272,"identity":"15fbdf8e-d6d6-4ba4-ac80-2df13589f12e","added_by":"auto","created_at":"2024-12-04 10:01:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4178930,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5179870/v1/e47c6d32-174b-44e1-a6b8-77b2ef7744de.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Application research on improving the uniformity of Zhike Taohua Powder based on powder modification technology","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eTraditional Chinese medicine powder is an important material basis for solid preparations of traditional Chinese medicine. Powder is one of the oldest traditional dosage forms with powder as the main form. There are a large number of records of powder in the ancient classic medical classics, Treatise on Febrile Diseases, Mingyi Bielu, and Shennong\u0026rsquo;s Herbal Classic \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. In addition, Chinese medicine powder is also an intermediate for the preparation of other dosage forms, which is of great significance for the preparation and development of dosage forms \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. However, due to the complexity of its physical and chemical properties, and the different properties of the powder composition of traditional Chinese medicine compound, often lead to poor mixing uniformity and other pharmaceutical problems \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe characteristics of traditional Chinese medicine powder affect the preparation of mixed molding \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Under the guidance of the theory of traditional Chinese medicine, combined with the powder material science and the production and processing methods of Chinese herbal pieces, the introduction of traditional Chinese medicine powder modification technology can solve the problems of poor fluidity and strong hygroscopicity of traditional Chinese medicine powder preparations \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Powder modification technology is to use physical and chemical methods to change the state of the powder itself, and then change the physical and chemical properties, so as to improve the prescription function \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. The powder modification technology is applied to the solid preparation of traditional Chinese medicine, and the pharmaceutical method is improved from the perspective of powder science. It is of great significance to improve the pharmacodynamic function of traditional Chinese medicine prescription and the secondary application of traditional Chinese medicine products, so that the traditional preparation of traditional Chinese medicine is closer to the modern preparation \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Among them, particle coating technology is one of the commonly used methods for powder modification. Shell particles with smaller particle sizes are orderly embedded on the surface of nuclear particles with larger particle sizes through equipment such as ball mills and ultrafine pulverizers. In this process, the particle size ratio of 'shell-core' structure should be reasonably controlled to achieve the purpose of modification \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. So as to improve the overall powder characterization properties of the prescription, and at the same time, it can achieve the purpose of correcting bad smell and achieving ideal drug release speed \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Chen, et al. \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e introduced magnesium stearate, a medicinal excipient, to prepare 'core-shell' composite particles by ultrafine grinding with \u003cem\u003eTaraxacum mongolicum\u003c/em\u003e Hand. -Mazz. and \u003cem\u003eLobaria retigera\u003c/em\u003e Trevis. fine powder. It was found that when the amount of magnesium stearate was 2% and the compounding time was 3 min, the prepared composite particles could significantly improve the problems of poor fluidity and uneven composition of powder raw materials.\u003c/p\u003e \u003cp\u003eZhike Taohua Powder (ZTP) is a cough relieving and expectorant agent successfully developed on the basis of the folk prescription 'Taohua Powder' for the treatment of cough \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. It is composed of \u003cem\u003eFritillaria cirrhosa\u003c/em\u003e D.Don, \u003cem\u003eMoschus berezovskii\u003c/em\u003e Flerov, \u003cem\u003eBorneolum Syntheticum\u003c/em\u003e, \u003cem\u003eMentha haplocalyx\u003c/em\u003e Briq., \u003cem\u003eCinnabaris\u003c/em\u003e, \u003cem\u003ePinellia ternate\u003c/em\u003e (Thunb.) Breit., \u003cem\u003eGypsum Fibrosum Preparatum\u003c/em\u003e. It has the effects of clearing lung, resolving phlegm, relieving cough, dredging orifices and cooling, and relieving convulsion. Antitussive for pertussis and chronic cough, measles complicated with pneumonia \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. In the preparation process of ZTP, due to the differences in the source and properties of the raw materials of traditional Chinese medicine compound, the particle size, density and chroma of each medicinal material after crushing are different, which has a great influence on the uniformity of the effective components of the preparation \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. In the previous study, it was found that the fluidity of mint raw materials was poor, which was easy to cause the uneven content of components in the whole prescription. In this study, from the perspective of Chinese medicine powder modification, combined with the concept of drug-assisted integration, powder modification was carried out on the fine powder of decoction pieces that caused the defects of prescription preparations, in order to solve the problems of mixing and uniformity of ZTP. The research framework is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"2. Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Instruments, drugs, and reagents\u003c/h2\u003e \u003cp\u003eQE-300 high-speed ultrafine pulverizer (Zhejiang Yili Industry \u0026amp; Trade Co., Ltd.); yS3010 spectrophotometer (Shenzhen Sanenshi Technology Co., Ltd.); iUAZ3000 Malvern laser particle size analyzer (Malvern Panaco); vEGA3 scanning electron microscope (Tesco Trading (Shanghai) Co., Ltd.); DSA-100 optical contact angle measuring instrument, (KRUSS, Germany); 769YP-5T multifunctional tableting machine (Shanghai Pressure Reducer Factory Co., Ltd.); bP-121S 100 thousandth of an analytical balance, (Beijing Sedolis Instrument System Co., Ltd.); tENSOR-27 Fourier Transform Infrared Spectrometer (Bruker, Germany); zRS-8LD intelligent dissolution tester, (Tianjin Tianda Tianfa Technology Co., Ltd.); thermo Scientific UltiMate 3000 HPLC, (Thermo Scientific, USA).\u003c/p\u003e \u003cp\u003e \u003cem\u003eF. cirrhosa\u003c/em\u003e (No.: 20230201), \u003cem\u003eM. berezovskii\u003c/em\u003e (No.: 20210506), \u003cem\u003eB. Syntheticum\u003c/em\u003e (No.: 20230315), \u003cem\u003eM. haplocalyx\u003c/em\u003e (No.: 20230410), \u003cem\u003eCinnabaris\u003c/em\u003e (No.: 20230304), \u003cem\u003eP. ternate\u003c/em\u003e (No.: 20230410), \u003cem\u003eGypsum F. Preparatum\u003c/em\u003e (No.: 20230315) were purchased from Shaanxi Xingshengde Pharmaceutical Co., Ltd. Methanol (chromatographic grade, U.S., Fisher), water (China, Wahaha).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Investigation of powder properties of prescription medicinal materials and extraction of pharmaceutical defects\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Sample preparation\u003c/h2\u003e \u003cp\u003eIn this prescription, \u003cem\u003eM. berezovskii\u003c/em\u003e is a valuable medicine, and crushing requires more drugs. \u003cem\u003eM. berezovskii\u003c/em\u003e is not easy to crush and investigate, so the remaining six kinds are investigated. Six kinds of decoction pieces such as \u003cem\u003eF. cirrhosa\u003c/em\u003e were taken and placed in a high-speed pulverizer. After crushing, the crude powder of the decoction pieces of the medicinal materials could pass through the No. 3 sieve. The 200 g crude powder of the decoction pieces was placed in an ultra-fine pulverizer for micro-pulverization (the temperature of the crushing chamber was-5\u0026deg;C, the grinding filling rate of the fine powder was 75%, and the crushing time was 60 min). Samples were taken at intervals, dried and stored for use; at the same time, the preparation of six kinds decoction pieces fine powder (all through the No.5 sieve, and can pass through the No.6 sieve no less than 95% of the powder).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2 Particle size investigation\u003c/h2\u003e \u003cp\u003eThe particle size of each sample was determined with the help of the dry method of Microtrac laser particle size analyzer (S3500), and the characteristic values of different particle size distributions (\u003cem\u003ed\u003c/em\u003e10, \u003cem\u003ed\u003c/em\u003e50, \u003cem\u003ed\u003c/em\u003e90) of each sample were recorded, and the regression equations between d90 (\u003cem\u003eY\u003c/em\u003e) and pulverization time (\u003cem\u003eX\u003c/em\u003e) were further established to explore the pulverization pattern of the medicinal tablets.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.2.3 Determination of fluidity and wettability\u003c/h2\u003e \u003cp\u003eThe angle of repose of each sample was measured by BT-100 powder characteristic analyzer to further evaluate the fluidity of the powder. Put different samples on the sieve net, open the instrument to make the sample fall slowly until the sample presents the highest cone, and use the protractor to measure the angle of repose of the sample near the cone. The contact angle of each sample was measured by K100C automatic surface tension and contact angle tester. Further judge the wettability of the powder. 0.2 g of the sample to be tested was taken, and the sample was prepared into a circular tablet with a diameter of about 10 mm and a hardness greater than 60 N by a multifunctional tabletting machine. The contact angle of each sample was determined by using pure water as the contact medium.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.2.4 Determination of bulk density of fine powder of medicinal materials\u003c/h2\u003e \u003cp\u003eThe bulk density of fine powder of each medicinal material was investigated and determined by fixed volume. The samples of each medicinal material were sampled according to the FDA's 'Drug Sampling Guidelines', and the samples were slowly dropped from the fixed funnel to form the highest cone at the bottom of the funnel. Samples were taken from the upper, middle, lower, anterior, posterior, left and right seven sites of the cone, respectively. The samples were slowly dropped into a 1.5 mL EP tube through a fixed funnel until the EP tube was filled and the excess samples were scraped. The bulk density of each sample was calculated by the ratio of mass and volume. Each point was sampled three times and the bulk density of the sample was measured in parallel.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.2.5 Determination of color difference of fine powder of medicinal materials\u003c/h2\u003e \u003cp\u003eThe color difference of the fine powder of the decoction pieces was measured by a spectrophotometer. The methodology of six kinds of medicinal materials was investigated, and their precision, repeatability and stability were investigated.\u003c/p\u003e \u003cp\u003eThe samples were taken according to the above FDA sampling method, and seven different sites of the fine powder of the six medicinal materials were taken for testing. Seven groups of samples of fine powder of medicinal materials were placed in the sample instrument of spectrophotometer. After calibrating the instrument, the sample pool was installed to start the measurement. The CIE1976 color space was selected, and the color difference of fine powder was judged by calculating the comprehensive chroma value ΔE*ab=[(ΔL*)\u003csup\u003e2\u003c/sup\u003e+(Δa*)\u003csup\u003e2\u003c/sup\u003e+(Δb*)\u003csup\u003e2\u003c/sup\u003e]\u003csup\u003e1/2\u003c/sup\u003e. Each group was measured 3 times in parallel, and the comprehensive color difference ΔE*ab was calculated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.2.6 Investigation on the fluidity of prescription excluding some medicinal materials\u003c/h2\u003e \u003cp\u003eThe fine powder of the medicinal materials with large differences was removed, and the angle of repose of each sample was measured by BT-100 powder characteristic analyzer to further evaluate the key factors affecting the fluidity of the prescription.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Establishment of modification process\u003c/h2\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003e2.3.1 Investigation of shell particle size\u003c/h2\u003e \u003cp\u003eThe fine powder of \u003cem\u003eP. ternate\u003c/em\u003e was used as the initial material to be put into the ultrafine pulverizer (temperature-5\u0026deg;C, filling rate 80%, amplitude 5.5 mm) for intermittent sampling. The particle size of the powder in different time periods was measured, and the change rule between the particle size of the powder and the grinding time was investigated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e2.3.2 Investigation of nuclear particle size\u003c/h2\u003e \u003cp\u003eThe fine powder of \u003cem\u003eM. haplocalyx\u003c/em\u003e was used as the initial material to be put into the ultrafine pulverizer (temperature-5\u0026deg;C, filling rate 80%, amplitude 5.5 mm) for intermittent sampling. The particle size of the powder in different time periods was measured, and the change rule between the particle size of the powder and the grinding time was investigated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e2.3.3 Investigation of powder properties of composite particles\u003c/h2\u003e \u003cp\u003eThe formation of 'shell-core' composite particles: The prepared shell particle \u003cem\u003eP. ternate\u003c/em\u003e and the nuclear particle \u003cem\u003eM. haplocalyx\u003c/em\u003e were mixed evenly according to the prescription ratio, and then put into the ultra-fine crusher, and the ultra-fine grinding was obtained at-5\u0026deg;C. According to the results of the regression equation of the crushing time-particle size, the shell particles and the nuclear particle fine powder were compounded in the ultrafine pulverizer at 2, 4, and 6 min according to the above preparation method, and the powder index was characterized.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e2.3.4 Investigation of physical properties of composite particles\u003c/h2\u003e \u003cdiv id=\"Sec16\" class=\"Section4\"\u003e \u003ch2\u003e2.3.4.1 FTIR determination\u003c/h2\u003e \u003cp\u003eAppropriate amount of KBr was taken and placed in a drying oven for 4 h. Then the sample to be tested and the dried KBr were taken to the agate mortar at a ratio of 1 : 100 for fine mixing and tableting, and the infrared spectrum of the sample was determined.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section4\"\u003e \u003ch2\u003e2.3.4.2 SEM microstructure determination\u003c/h2\u003e \u003cp\u003eA small amount of sample particles to be tested were placed on the sample holder and gilded at a working current of 10 mA and a working voltage of 4 mV for 20 s. The morphology of the particles was observed by scanning electron microscope.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Study on the regression of composite particles to the powder properties of the whole party\u003c/h2\u003e \u003cp\u003eThe modified decoction pieces composite particles were returned to the whole prescription, and mixed evenly with the remaining powder of the prescription according to the prescription ratio as ZTP; the original prescription powder of ZTP was prepared according to the preparation method of the original prescription. The particle size, color difference, bulk density, uniformity of active ingredient content and in vitro dissolution of active ingredients of two different powders were investigated respectively, and the effect of powder modification technology was evaluated from the overall level of prescription. The investigation of particle size, fluidity, wettability, bulk density and color difference is consistent with the previous method .\u003c/p\u003e \u003cp\u003eIn this prescription, \u003cem\u003eF. cirrhosa\u003c/em\u003e, \u003cem\u003eP. ternate\u003c/em\u003e, and \u003cem\u003eM. haplocalyx\u003c/em\u003e are rich in nucleosides. Nucleosides are the basic substances to maintain life activities, and they are also one of the key pharmacodynamic components of commonly used animal medicines. This study intends to determine the content of nucleosides in the prescription to determine the uniformity of the prescription content.\u003c/p\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1 Investigation on the content uniformity of nucleosides\u003c/h2\u003e \u003cdiv id=\"Sec20\" class=\"Section4\"\u003e \u003ch2\u003e2.4.1.1 Preparation of test solution\u003c/h2\u003e \u003cp\u003eAccording to the FDA's 'drug sampling guidelines' sampling method, 7 groups of samples were taken from the original prescription of ZTP and the compound prescription of ZTP.3.0 g of the sample was accurately weighed and placed in a 50 mL conical bottle. 30 mL of purified water was added, weighed, and ultrasonically treated for 60 min. After cooling, the purified water was used to make up for the lost quality. Shake well, transfer the solution to the centrifuge tube, 10000 r/min, centrifuge for 10 min, filter, filter with 0.22 \u0026micro;m microporous membrane, and obtain the test solution.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section4\"\u003e \u003ch2\u003e2.4.1.2 Preparation of reference solution\u003c/h2\u003e \u003cp\u003eThe appropriate amount of uracil, inosine, uridine, adenosine, guanosine, adenine and thymidine was weighed and dissolved with purified water. The mixed reference solution of uracil (11.16 \u0026micro;g/mL), inosine (11.20 \u0026micro;g/mL), uridine (21.56 \u0026micro;g/mL), adenosine (13.54 \u0026micro;g/mL), guanosine (16.18 \u0026micro;g/mL), adenine (36.40 \u0026micro;g/mL) and thymidine (4.55 \u0026micro;g/mL) was prepared by dilution. The mixed reference solution was filtered with 0.22 \u0026micro;m microporous membrane, and the filtrate was taken to obtain the reference solution.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section4\"\u003e \u003ch2\u003e2.4.1.3 Preparation of negative sample solution\u003c/h2\u003e \u003cp\u003eThe medicinal materials containing nucleosides were removed, and 3.0 g was accurately weighed and placed in a 50 mL conical flask, 30 mL of purified water was added, weighed, and ultrasonically treated for 60 min. After cooling, the purified water was used to supplement the lost quality, shaken, and the solution was transferred to a centrifuge tube. 10000 r/min, centrifuged for 10 min, filtered, filtered with a 0.22 \u0026micro;m microporous membrane, and the negative sample solution was obtained.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section4\"\u003e \u003ch2\u003e2.4.1.4 Chromatographic condition\u003c/h2\u003e \u003cp\u003eAgilent 5 TC-C18 (2) 250\u0026times;4.6 mm, 5 \u0026micro;m chromatographic column was used. The mobile phase was methanol (A): water (B), gradient elution 0\u0026thinsp;~\u0026thinsp;5 min, A: 1%~2%; 5\u0026thinsp;~\u0026thinsp;15 min, A: 2%; 15\u0026thinsp;~\u0026thinsp;20 min, A: 2%~5%; 20\u0026thinsp;~\u0026thinsp;30 min, A: 5%~15%; 30\u0026thinsp;~\u0026thinsp;35 min, A: 15%; 35\u0026thinsp;~\u0026thinsp;40 min, A: 15% ~20%; 40\u0026thinsp;~\u0026thinsp;45 min, A: 20%~1%; the flow rate was 0.8 mL/min. The detection wavelength was 260 nm. The injection volume was 20 \u0026micro;L, and the column temperature was 35\u0026deg;C. The time was 45 min \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2 Homogeneity of \u003cem\u003eCinnabaris\u003c/em\u003e content\u003c/h2\u003e \u003cp\u003eAccording to the FDA's 'Drug Sampling Guidelines' sampling method, 7 groups of samples were taken from the original prescription of ZTP and the compound prescription of ZTP, and the content of cinnabar was determined. About 1.0 g of each sample particle was accurately weighed and placed in a Kjeldahl flask, and 20 mL of sulfuric acid and 3 g of potassium nitrate were added for heating and digestion. After that, 3 g of potassium nitrate was added every 30 min until the solution was nearly colorless. Then the solution was cooled to room temperature and transferred to a conical flask. The flask was washed with 50 mL of distilled water, and the washing solution was incorporated into the conical flask. The 1% potassium permanganate solution was added dropwise to pink, and the 2% ferrous sulfate solution was added dropwise to red until it disappeared. Then 2 mL of ammonium ferric sulfate indicator solution was added, and the solution was titrated with ammonium thiocyanate to orange red. The consumption volume of the titration solution was recorded. Each 1 mL ammonium thiocyanate titration solution (0.1 mol/L) is equivalent to 11.63 mg of mercury sulfide (HgS) \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003e2.4.3 Structural stability evaluation\u003c/h2\u003e \u003cp\u003eIn order to evaluate the structural stability of the 'shell-core' coated composite particles, this study simulated the collision and oscillation that the preparation may be subjected to during transportation. A square area of 2 cm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e in the slide was selected as the experimental area. After the conductive tape was pasted, it was divided into 4\u0026times;4 small grids. An appropriate amount of the sample to be tested was evenly blown down in the experimental area of the conductive tape. The transparent tape was used to fix the slide. The low frequency (50 Hz), medium frequency (100 Hz) and high frequency (300 Hz) were successively intervened for 60 min by a constant temperature oscillator. The microscopic morphological changes were observed under a scanning electron microscope \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003e2.4.4 In vitro dissolution determination\u003c/h2\u003e \u003cp\u003eAccording to the 2020 edition of the 'Chinese Pharmacopoeia' Volume IV 'General Rule 0931', the dissolution was determined by slurry method. The original prescription of ZTP and the compound prescription of ZTP were accurately weighed 10 g, and a total of 3 parallel groups were taken for standby. The dissolution medium of the dissolution instrument was 900 mL of 0.1 mol/L hydrochloric acid, the working temperature was 37.5\u0026deg;C, the rotation speed was 100 r/min, and the dissolution method was slurry method. Samples were taken at 5, 10, 20, 30, 60, 90, 120, 150, 180, 210, and 240 min, 4 mL each time, and fresh dissolution medium with the same temperature and volume was supplemented. The sample was filtered by 0.22 um microporous membrane, and 20 \u0026micro;L sample was injected for determination, and the dissolution rate was calculated \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eAll date were expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). The results were analyzed by one-way ANOVA test using SPSS 17.0 software, followed by Dunnett\u0026rsquo;s test. A P value less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec29\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Investigation of powder properties of prescription medicinal materials and extraction of pharmaceutical defects\u003c/h2\u003e \u003cdiv id=\"Sec30\" class=\"Section3\"\u003e \u003ch2\u003e3.1.1 Particle size investigation\u003c/h2\u003e \u003cp\u003eAccording to the analysis of Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the particle size of \u003cem\u003eM. haplocalyx\u003c/em\u003e, \u003cem\u003eP. ternate\u003c/em\u003e, \u003cem\u003eF. cirrhosa\u003c/em\u003e, and \u003cem\u003eCinnabaris\u003c/em\u003e showed a trend of 'decrease-balance-increase'. The correlation coefficient between the particle size of each decoction piece and the grinding time was greater than 0.9, which proved that the ultrafine grinding time was closely related to the change of particle size. \u003cem\u003eM. haplocalyx\u003c/em\u003e, \u003cem\u003eP. ternate\u003c/em\u003e, \u003cem\u003eF. cirrhosa\u003c/em\u003e, and \u003cem\u003eCinnabaris\u003c/em\u003e reached the minimum particle size of 55.235, 36.552, 41.058, and 40.045 \u0026micro;m in 23.10, 20.00, 13.50, 9.31 min, respectively. \u003cem\u003eC. camphora\u003c/em\u003e and \u003cem\u003eGypsum F. Preparatum\u003c/em\u003e showed a trend of 'increase-balance-decrease', which was mainly attributed to the increase of surface free energy of decoction pieces particles under the action of high-speed collision and shear. In order to further ensure the overall stability, the particles will agglomerate with each other to further reduce the surface free energy, resulting in an increase in the particle size of decoction pieces. In summary, the particle size is closely related to the crushing time.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFitting equation of crushing time (t)-particle size (\u003cem\u003ed\u003c/em\u003e90) of prescription decoction pieces\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRegression equation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCorrelation coefficient \u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eX\u003c/em\u003e(min)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eY\u003c/em\u003e(\u0026micro;m)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eM. haplocalyx\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eY\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1471\u003cem\u003eX\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e-6.7952\u003cem\u003eX\u003c/em\u003e\u0026thinsp;+\u0026thinsp;133.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.923\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e55.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eC. camphora\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eY\u003c/em\u003e=-0.4271\u003cem\u003eX\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;+\u0026thinsp;18.95\u003cem\u003eX\u003c/em\u003e\u0026thinsp;+\u0026thinsp;199.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.948\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e409.518\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGypsum F. Preparatum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eY\u003c/em\u003e=-0.5053\u003cem\u003eX\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;+\u0026thinsp;16.77\u003cem\u003eX\u003c/em\u003e\u0026thinsp;+\u0026thinsp;108.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.936\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e248.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP. ternate\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eY\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.1708\u003cem\u003eX\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e-6.8334\u003cem\u003eX\u003c/em\u003e\u0026thinsp;+\u0026thinsp;104.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.932\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e36.552\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eF. cirrhosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eY\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.364\u003cem\u003eX\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e-10.169\u003cem\u003eX\u003c/em\u003e\u0026thinsp;+\u0026thinsp;112.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.975\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e41.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCinnabaris\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eY\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.102\u003cem\u003eX\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e-1.9646\u003cem\u003eX\u003c/em\u003e\u0026thinsp;+\u0026thinsp;49.505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.975\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e40.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec31\" class=\"Section3\"\u003e \u003ch2\u003e3.1.2 Determination of fluidity and wettability\u003c/h2\u003e \u003cp\u003eThe angle of repose and contact angle of powder are important indexes to judge the fluidity and wettability of powder. The smaller the angle of repose and contact angle, the better the fluidity and wettability of the powder, and also indirectly affect the preparation and stability of the subsequent preparations. According to the comparison data of angle of repose and contact angle in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the angle of repose of \u003cem\u003eM. haplocalyx\u003c/em\u003e and \u003cem\u003eC. camphora\u003c/em\u003e was large, and the fluidity of the powder was poor, which indirectly affected the overall prescription pharmaceutics evaluation (angle of repose\u0026thinsp;\u0026gt;\u0026thinsp;45\u0026deg;). In addition, the contact angle of the powder of each prescription is large and the wettability is poor, which leads to the defects of the whole prescription preparation.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDetermination results of angle of repose and contact angle of Zhike Taohua powder mixture and fine powder of each decoction pieces (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAngle of repose (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eContact angle (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eM. haplocalyx\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e46.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e66.61\u0026thinsp;\u0026plusmn;\u0026thinsp;2.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eC. camphora\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e47.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e78.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGypsum F. Preparatum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e61.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e59.92\u0026thinsp;\u0026plusmn;\u0026thinsp;3.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP. ternate\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e44.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e44.77\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eF. cirrhosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e33.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e92.96\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCinnabaris\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e41.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e103.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOriginal prescription\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e45.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.491\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e53.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.518\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec32\" class=\"Section3\"\u003e \u003ch2\u003e3.1.3 Determination of bulk density of fine powder of medicinal materials\u003c/h2\u003e \u003cp\u003eThe average bulk density values of the seven sampling points of \u003cem\u003eM. haplocalyx\u003c/em\u003e, \u003cem\u003eC. camphora\u003c/em\u003e, \u003cem\u003eGypsum F. Preparatum\u003c/em\u003e, \u003cem\u003eP. ternate\u003c/em\u003e, \u003cem\u003eF. cirrhosa\u003c/em\u003e, and \u003cem\u003eCinnabaris\u003c/em\u003e are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Further calculation of the bulk density RSD values of the seven sampling points of the single-flavor decoction pieces fine powder is 7.48%, 5.23%, 0.61%, 0.74%, 0.59%, and 0.21%. The comparison results of the bulk density of the seven sampling points of the six-flavor decoction pieces are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The bulk density of seven sampling points of \u003cem\u003eM. haplocalyx\u003c/em\u003e and \u003cem\u003eC. camphora\u003c/em\u003e were quite different.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDetermination results of bulk density of fine powder of medicinal materials (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eM. haplocalyx\u003c/em\u003e (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eC. camphora\u003c/em\u003e (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eGypsum F. Preparatum\u003c/em\u003e (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP. ternate\u003c/em\u003e (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eF. cirrhosa\u003c/em\u003e (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eCinnabaris\u003c/em\u003e (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.303\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.269\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.967\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.579\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.752\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.153\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.287\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.296\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.973\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.575\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.757\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.158\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.297\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.298\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.966\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.570\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.746\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.163\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFront\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.278\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.306\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.968\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.575\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.750\u0026thinsp;\u0026plusmn;\u0026thinsp;0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.166\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.342\u0026thinsp;\u0026plusmn;\u0026thinsp;0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.268\u0026thinsp;\u0026plusmn;\u0026thinsp;0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.960\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.580\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.746\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.168\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.277\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.291\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.955\u0026thinsp;\u0026plusmn;\u0026thinsp;0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.568\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.754\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.162\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.293\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.300\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.966\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.572\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.747\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.173\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRSD (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec33\" class=\"Section3\"\u003e \u003ch2\u003e3.1.4 Determination of color difference of fine powder of medicinal materials\u003c/h2\u003e \u003cp\u003eThe precision, repeatability and stability of six kinds of medicinal powder samples of ZTP were determined. The results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMethodological results of color difference of fine powder of medicinal materials\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eM. haplocalyx\u003c/em\u003e RSD (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eC. camphora\u003c/em\u003e RSD (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eGypsum F. Preparatum\u003c/em\u003e RSD (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP. ternate\u003c/em\u003e RSD (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eF. cirrhosa\u003c/em\u003e RSD (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eCinnabaris\u003c/em\u003e RSD (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrecision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRepeatability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.683\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.154\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.129\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe color difference ΔE * dE * of the seven sampling points of the six medicinal materials of ZTP was measured three times, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. From Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the average color difference values of seven sampling points of six medicinal materials, such as \u003cem\u003eM. haplocalyx\u003c/em\u003e, \u003cem\u003eC. camphora\u003c/em\u003e, \u003cem\u003eGypsum F. Preparatum\u003c/em\u003e, \u003cem\u003eP. ternate\u003c/em\u003e, \u003cem\u003eF. cirrhosa\u003c/em\u003e, and \u003cem\u003eCinnabaris\u003c/em\u003e were 58.223, 104.628, 101.916, 103.456, 101.917, and 85.688, respectively. The RSD values of color difference of seven sampling points of single decoction pieces fine powder were calculated to be 4.012%, 1.214%, 0.005%, 0.011%, 0.125%, and 0.009%. The comparison results of color difference of seven sampling points of decoction pieces fine powder are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of color difference of fine pink of six medicinal materials of ZTP (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eM. haplocalyx\u003c/em\u003e (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eC. camphora\u003c/em\u003e (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eGypsum F. Preparatum\u003c/em\u003e (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP. ternate\u003c/em\u003e (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eF. cirrhosa\u003c/em\u003e (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eCinnabaris\u003c/em\u003e (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.521\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104.668\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.929\u0026thinsp;\u0026plusmn;\u0026thinsp;0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103.474\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e101.638\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e85.701\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.242\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102.692\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.929\u0026thinsp;\u0026plusmn;\u0026thinsp;0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103.462\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e101.920\u0026thinsp;\u0026plusmn;\u0026thinsp;0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e85.694\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.054\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103.790\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.929\u0026thinsp;\u0026plusmn;\u0026thinsp;0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103.467\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e101.947\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e85.692\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFront\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.497\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105.222\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.918\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103.448\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e101.952\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e85.689\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.483\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105.225\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.915\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103.453\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e101.975\u0026thinsp;\u0026plusmn;\u0026thinsp;0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e85.686\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.418\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106.683\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.919\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103.449\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e102.003\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e85.681\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.345\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104.130\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.922\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103.442\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e101.999\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e85.678\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRSD (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBy examining the bulk density and color difference of the fine powder of medicinal materials, the uniformity of the powder was measured according to the RSD value of the bulk density and color difference. When the RSD of bulk density and color difference is large, it is proved that the uniformity of the fine powder is poor and the mixing degree is low. According to the above experiments, it was found that \u003cem\u003eM. haplocalyx\u003c/em\u003e and \u003cem\u003eC. camphora\u003c/em\u003e fine powders had poor uniformity and low mixing degree. Combined with the results of angle of repose and contact angle, it was indicated that the two may lead to uneven mixing of Zhike Taohua powder and poor uniformity of the drug. In order to further determine the key factors affecting the uniformity of ZTP, the fine powder of medicinal materials with poor fluidity was removed, and the angle of repose of the mixed powder was determined to determine the main influencing factors.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec34\" class=\"Section3\"\u003e \u003ch2\u003e3.1.5 Investigation on the fluidity of prescription excluding some medicinal materials\u003c/h2\u003e \u003cp\u003eAccording to the above experiments, it is found that \u003cem\u003eM. haplocalyx\u003c/em\u003e, \u003cem\u003eC. camphora\u003c/em\u003e, and \u003cem\u003eGypsum F. Preparatum\u003c/em\u003e have a large angle of repose and poor powder fluidity, which may lead to poor mixing of prescription drugs. Therefore, \u003cem\u003eM. haplocalyx\u003c/em\u003e, \u003cem\u003eC. camphora\u003c/em\u003e, and \u003cem\u003eGypsum F. Preparatum\u003c/em\u003e were removed in turn, and the angle of repose of the mixture of the remaining drugs was determined to judge the drug fluidity.\u003c/p\u003e \u003cp\u003eThe results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. \u003cem\u003eM. haplocalyx\u003c/em\u003e powder is the key factor affecting the uniformity of ZTP, which is an important reason for the poor fluidity of the prescription and the uneven uniformity of the preparation. In order to further improve the fluidity of the powder and the uniformity of drug mixing, \u003cem\u003eP. ternate\u003c/em\u003e with excellent fluidity and small particle size was selected as the shell particles. Through the mechanical particle composite method, the 'core-shell' coated composite particles were prepared with \u003cem\u003eP. ternate\u003c/em\u003e as the shell particles and the fine powder of \u003cem\u003eM. haplocalyx\u003c/em\u003e pieces as the core particles, in order to improve the fluidity of the whole prescription and improve the uniformity of the preparation of ZTP.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRemoving the angle of repose of three kinds of medicinal powder prescription (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAngle of repose (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemoval \u003cem\u003eM. haplocalyx\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e42.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemoval \u003cem\u003eC. camphora\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e45.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemoval \u003cem\u003eGypsum F. Preparatum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e46.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec35\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Establishment of modification process\u003c/h2\u003e \u003cdiv id=\"Sec36\" class=\"Section3\"\u003e \u003ch2\u003e3.2.1 Investigation of shell particle size\u003c/h2\u003e \u003cp\u003eThe change rule of shell particle crushing time is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Among them, \u003cem\u003ed\u003c/em\u003e90 is the particle size, and the smaller the \u003cem\u003ed\u003c/em\u003e90 is, the smaller the particle size is. It can be seen from Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e that with the extension of superfine grinding time, the particle size of \u003cem\u003eP. ternate\u003c/em\u003e decreased gradually. Based on the particle size of \u003cem\u003ed\u003c/em\u003e10 and \u003cem\u003ed\u003c/em\u003e50, the superfine grinding time of \u003cem\u003eP. ternate\u003c/em\u003e by shell particle method was determined to be 20 min.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec37\" class=\"Section3\"\u003e \u003ch2\u003e3.2.2 Investigation of nuclear particle size\u003c/h2\u003e \u003cp\u003eThe variation of nuclear particle crushing time is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. With the progress of the crushing process, the particle size of \u003cem\u003eM. haplocalyx\u003c/em\u003e gradually decreased. Combining the particle size comparison of \u003cem\u003ed\u003c/em\u003e10 and \u003cem\u003ed\u003c/em\u003e50, the \u003cem\u003eM. haplocalyx\u003c/em\u003e fine powder can be directly determined as a nuclear particle.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec38\" class=\"Section3\"\u003e \u003ch2\u003e3.2.3 Investigation of powder properties of composite particles\u003c/h2\u003e \u003cp\u003eThe results of material particle fluidity and wettability under different superfine grinding time are shown in Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e. The fluidity of the modified composite particle material fine powder was improved compared with the original two-flavor decoction pieces mixed fine powder. The material showed the best fluidity and wettability when ultrafine grinding for 4 min. It can be preliminarily considered that the preparation process of ultrafine grinding for 4 min is better. Subsequently, IR, SEM and other techniques were introduced to investigate the physical properties of the composite particles and observe the microstructure of the materials.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInvestigation results of powder properties of composite particles (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAngle of repose (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eContact angle (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite particle 2 min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e43.617\u0026thinsp;\u0026plusmn;\u0026thinsp;0.355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e82.763\u0026thinsp;\u0026plusmn;\u0026thinsp;1.101\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite particle 4 min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e41.420\u0026thinsp;\u0026plusmn;\u0026thinsp;0.380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e79.090\u0026thinsp;\u0026plusmn;\u0026thinsp;1.629\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite particle 6 min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e45.190\u0026thinsp;\u0026plusmn;\u0026thinsp;0.829\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e84.837\u0026thinsp;\u0026plusmn;\u0026thinsp;0.280\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec39\" class=\"Section3\"\u003e \u003ch2\u003e3.2.4 Investigation of physical properties of composite particles\u003c/h2\u003e \u003cdiv id=\"Sec40\" class=\"Section4\"\u003e \u003ch2\u003e3.2.4.1 FTIR determination\u003c/h2\u003e \u003cp\u003eThe infrared results are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e. \u003cem\u003eP. ternate\u003c/em\u003e has one characteristic peak at 3000\u0026thinsp;\u0026minus;\u0026thinsp;2500 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and three characteristic peaks at 1500\u0026thinsp;\u0026minus;\u0026thinsp;500 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. Among the composite particles of ultrafine grinding for 2, 4, and 6 min, only the composite particles of 4 min showed the same characteristic peaks at these wavelengths and the peak intensity was high, indicating that the composite particles of ultrafine grinding for 4 min were well coated.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec41\" class=\"Section4\"\u003e \u003ch2\u003e3.2.4.2 SEM microstructure determination\u003c/h2\u003e \u003cp\u003eThe SEM results are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e. The shape of the particles of \u003cem\u003eP. ternate\u003c/em\u003e is mostly spherical, and the particles of \u003cem\u003eM. haplocalyx\u003c/em\u003e are irregular flakes. The microscopic characteristics of the particles of \u003cem\u003eP. ternate\u003c/em\u003e and \u003cem\u003eM. haplocalyx\u003c/em\u003e can be clearly observed in the electron microscope of the physical mixture diagram, and no new structure is found, indicating that there is only a simple mixing relationship between the two kinds of medicinal particles in the physical mixture. In Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e, the B, C and D composite particles show a microscopic morphology completely different from the physical mixture. The composite particles are mostly agglomerates with a rough surface and a compact structure. The composite particles of 4 min can be observed. The spherical particles are coated on the periphery of the irregular sheet structure to form a agglomerated particle with a rough surface and a compact structure. The composite 2 min particles are larger and the coating structure is less compact, and the composite 6 min particles show a partially coated state. It shows that the particle design technology changes the microstructure of \u003cem\u003eM. haplocalyx\u003c/em\u003e, and the prepared composite particles form a new microstructure. Based on the results of infrared measurement and scanning electron microscopy, it was determined that the composite particles crushed for 4 min had a better 'core-shell' coating model.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec42\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Study on the regression of composite particles to the powder properties of the whole party\u003c/h2\u003e \u003cdiv id=\"Sec43\" class=\"Section3\"\u003e \u003ch2\u003e3.3.1 Particle size investigation\u003c/h2\u003e \u003cp\u003eThe particle size of the original prescription of ZTP and the compound prescription of ZTP were determined. The results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e. After adding ultrafine composite particles, the particle size of the composite prescription decreased significantly.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of particle size distribution (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ed\u003c/em\u003e10(\u0026micro;m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ed\u003c/em\u003e50(\u0026micro;m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ed\u003c/em\u003e90(\u0026micro;m)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOriginal prescription\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e23.503\u0026thinsp;\u0026plusmn;\u0026thinsp;2.946\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e158.500\u0026thinsp;\u0026plusmn;\u0026thinsp;6.646\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e238.733\u0026thinsp;\u0026plusmn;\u0026thinsp;5.532\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompound prescription\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.490\u0026thinsp;\u0026plusmn;\u0026thinsp;0.714\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e142.267\u0026thinsp;\u0026plusmn;\u0026thinsp;1.665\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e225.700\u0026thinsp;\u0026plusmn;\u0026thinsp;0.755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec44\" class=\"Section3\"\u003e \u003ch2\u003e3.3.2 Investigation of fluidity and wettability\u003c/h2\u003e \u003cp\u003eThe angle of repose and contact angle of the original prescription of ZTP and the compound prescription of ZTP were measured, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e. The fluidity and wettability of the compound prescription of ZTP were improved to a certain extent, and the compound prescription of ZTP could better improve the deficiency of the original prescription.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of angle of repose and contact angle distribution (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAngle of repose (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eContact angle (\u0026deg;)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOriginal prescription\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e45.423\u0026thinsp;\u0026plusmn;\u0026thinsp;0.491\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e53.043\u0026thinsp;\u0026plusmn;\u0026thinsp;1.518\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompound prescription\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e42.173\u0026thinsp;\u0026plusmn;\u0026thinsp;0.365\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e44.833\u0026thinsp;\u0026plusmn;\u0026thinsp;0.917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec45\" class=\"Section3\"\u003e \u003ch2\u003e3.3.3 Investigation of bulk density and color difference uniformity\u003c/h2\u003e \u003cp\u003eThe results of bulk density are shown in Table\u0026nbsp;\u003cspan refid=\"Tab10\" class=\"InternalRef\"\u003e10\u003c/span\u003e. The bulk density of the compound prescription of ZTP increased, which may be due to the smaller particle size of the compound prescription of ZTP, and it was found that the density of the 7 sampling points of the compound prescription of ZTP fluctuated less (RSD\u0026thinsp;=\u0026thinsp;0.664%), indicating that the mixing uniformity between the particles of ZTP was significantly improved. The color difference results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab11\" class=\"InternalRef\"\u003e11\u003c/span\u003e. The color difference ΔE*ab can be used to investigate the mixing uniformity of the two samples. The greater the color difference fluctuation of the sample, the worse the mixing uniformity. The color difference of the samples at 7 sampling points of the compound prescription of ZTP fluctuated slightly (RSD\u0026thinsp;=\u0026thinsp;0.134%), which once again proved that the particles of the compound prescription were well mixed. The results of comprehensive bulk density and color difference showed that the uniformity of the compound prescription of ZTP was significantly improved.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab10\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 10\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of bulk density measurement (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCompound prescription (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOriginal prescription (g/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.750\u0026thinsp;\u0026plusmn;\u0026thinsp;0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.637\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.747\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.647\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.750\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.637\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFront\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.719\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.634\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.714\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.637\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.791\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.637\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.752\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.635\u0026thinsp;\u0026plusmn;\u0026thinsp;0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRSD (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.418\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab11\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 11\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of color difference measurement (\u003cem\u003ex̄\u003c/em\u003e\u0026plusmn;s, n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCompound prescription (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOriginal prescription (ΔE*ab)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.898\u0026thinsp;\u0026plusmn;\u0026thinsp;0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.866\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.965\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.337\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.073\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.742\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFront\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.098\u0026thinsp;\u0026plusmn;\u0026thinsp;0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.767\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.141\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.844\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.161\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.392\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.206\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.440\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRSD (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.935\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec46\" class=\"Section3\"\u003e \u003ch2\u003e3.3.4 Investigation on the content uniformity of nucleosides\u003c/h2\u003e \u003cdiv id=\"Sec47\" class=\"Section4\"\u003e \u003ch2\u003e3.3.4.1 Investigation of Exclusiveness\u003c/h2\u003e \u003cp\u003eThe test sample, mixed reference solution and negative sample solution were injected respectively according to the chromatographic conditions. The results are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e The negative solution had no interference.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec48\" class=\"Section4\"\u003e \u003ch2\u003e3.3.4.2 Drawing of standard curve\u003c/h2\u003e \u003cp\u003eThe standard curve was drawn with the content of each reference substance (\u0026micro;g) as the abscissa and the peak area as the ordinate. The regression equation was obtained, and the linear relationship was good. The results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab12\" class=\"InternalRef\"\u003e12\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab12\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 12\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLinear investigation of seven chemical constituents\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003elinear equation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRange of linearity/\u0026micro;g\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUracil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;129.78x-0.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01116\u0026thinsp;~\u0026thinsp;0.1674\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInosine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;34.275x\u0026thinsp;+\u0026thinsp;0.0064\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9997\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0112\u0026thinsp;~\u0026thinsp;0.168\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUridine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;53.259x-0.0433\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02156\u0026thinsp;~\u0026thinsp;0.3234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenosine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;85.563x-0.7031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9912\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01154\u0026thinsp;~\u0026thinsp;0.1731\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGuanosine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;49.38x\u0026thinsp;+\u0026thinsp;0.0128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01618\u0026thinsp;~\u0026thinsp;0.2427\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;84.611x-0.0951\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0364\u0026thinsp;~\u0026thinsp;0.546\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThymidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ey\u0026thinsp;=\u0026thinsp;46.252x-0.0017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9997\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00455\u0026thinsp;~\u0026thinsp;0.06825\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec49\" class=\"Section4\"\u003e \u003ch2\u003e3.3.4.3 Precision, repeatability, stability and recovery rate were investigated\u003c/h2\u003e \u003cp\u003eUnder the above chromatographic conditions, 10 \u0026micro;L of the mixed solution of the reference substance was accurately absorbed, and the sample was injected repeatedly for 6 times, and the peak area was recorded. The RSD of the calculated peak area was less than 3%, indicating that the precision was good. The same batch of samples of ZTP were divided into 6 parts of the same quality. The sample solution was prepared according to the preparation method of the test solution, and the peak area was determined according to the required verification method. The RSD of the peak area was less than 3%, indicating that the repeatability was good. The sample of Tianzhike Taohua Powder was taken and the test solution was prepared according to the preparation method of the test sample. The peak area was determined by chromatographic method at 0, 2, 4, 6, 8, 10, 12, and 24 h. The RSD of the peak area was calculated to be less than 3%, indicating that the sample had good stability at room temperature. Six portions of the same batch of samples with known content were taken, each of which was about 1.5 g. They were accurately weighed and placed in a conical flask with a stopper. An appropriate amount of each reference solution was accurately added to each portion, and purified water was precisely added to 30 mL. The samples were prepared according to the test method. According to the above method, the recovery rate was calculated to be between 95% and 105%, indicating that the method was accurate and stable.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec50\" class=\"Section4\"\u003e \u003ch2\u003e3.3.4.4 Investigation of sample content uniformity\u003c/h2\u003e \u003cp\u003eNucleoside content homogeneity is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e10\u003c/span\u003e. The contents of effective chemical components in 7 groups of samples in the original prescription of ZTP were quite different. The RSD of uracil, uridine, adenine, inosine, guanosine, thymidine and adenosine were 20.59%, 21.30%, 22.12%, 22.10%, 20.12%, 24.96% and 14.18%, respectively. The contents of effective chemical components in the compound prescription of ZTP were relatively close. The RSD of uracil, uridine, adenine, inosine, guanosine, thymidine and adenosine were 5.14%, 4.13%, 6.18%, 13.32%, 5.12%, 8.38% and 9.82%, respectively. It was found that the content of the original prescription was relatively low, which may be attributed to the uneven mixing of the original prescription powder, which further led to the low content of each determined component.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec51\" class=\"Section3\"\u003e \u003ch2\u003e3.3.5 Homogeneity of \u003cem\u003eCinnabaris\u003c/em\u003e content\u003c/h2\u003e \u003cp\u003eThe content uniformity of HgS in the particles of the two samples was evaluated by titration method. The results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab13\" class=\"InternalRef\"\u003e13\u003c/span\u003e. The RSD value of the physical mixture is 5.394%, the content distribution is discrete and the uniformity is poor. The content difference and RSD values of the composite particles are small, which are 1.115%, respectively. The dispersion of the content distribution is small and the uniformity is better than that of the physical mixture.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab13\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 13\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInvestigation on uniformity of \u003cem\u003eCinnabaris\u003c/em\u003e content\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpecimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSampling volume (g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVolume consumption (mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHgS measured amount (mg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRSD (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOriginal prescription\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.00094\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.550\u0026thinsp;\u0026plusmn;\u0026thinsp;0.191\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e41.287\u0026thinsp;\u0026plusmn;\u0026thinsp;2.227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.394\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompound prescription\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.00190\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.529\u0026thinsp;\u0026plusmn;\u0026thinsp;0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e41.037\u0026thinsp;\u0026plusmn;\u0026thinsp;0.458\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.115\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec52\" class=\"Section3\"\u003e \u003ch2\u003e3.3.6 Structural stability evaluation\u003c/h2\u003e \u003cp\u003eAfter low-frequency intervention, there is no significant change in the surface morphology of the composite particles. However, the vibration generated during the transportation of preparations in daily life is usually low-frequency oscillation, that is, the 'shell-core' coating structure of the composite particles meets the stability of the daily environment. When the intervention frequency was enhanced, it was found that some fine particles on the surface of the composite particles fell off, indicating that the ' shell-core ' coating structure between the composite particles was a soft coating relying on the molecular force between the particles, and did not change its material basis. The results are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e11\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec53\" class=\"Section3\"\u003e \u003ch2\u003e3.3.7 In vitro dissolution determination\u003c/h2\u003e \u003cp\u003eWith the increase of dissolution time, the dissolution behavior of the seven components in the original prescription of ZTP and the compound prescription of ZTP was basically the same. The dissolution was rapid in 0\u0026thinsp;~\u0026thinsp;30 min, and then after a period of platform period, the dissolution rate increased slightly near the end of dissolution time. The dissolution behavior of the original prescription of ZTP and the compound prescription of ZTP is basically the same, and the composite particles basically do not change the dissolution of the drug. The results are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig12\" class=\"InternalRef\"\u003e12\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"4 Conclusion and Discussion","content":"\u003cp\u003eThe traditional powder of traditional Chinese medicine adopts the preparation process of 'crushing-screening-mixing-sub-dose'. Since the compound powder is used as medicine, and the sources of medicinal materials in the prescription are different, it is very likely to lead to the appearance of pharmaceutical defects such as oral compliance and mixing uniformity, thus affecting the quality and stability of the preparation \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In this paper, the \u003cem\u003eM. haplocalyx\u003c/em\u003e and \u003cem\u003eP. ternate\u003c/em\u003e in the compound were taken as the research objects, and the particle design technology was introduced to study the preparation process of the \u003cem\u003eM. haplocalyx\u003c/em\u003e-\u003cem\u003eP. ternate\u003c/em\u003e composite particles, and the powder characteristics of the composite particles were characterized. The new idea of applying particle design technology to traditional Chinese medicine powder not only inherits the traditional form of drug delivery, but also solves the common problems that are easy to appear in traditional Chinese medicine powder, that is, particle design technology is suitable for the preparation process of contemporary powder and other solid preparation intermediates of traditional Chinese medicine \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAt the same time, based on the idea of quality comes from design', this study draws on particle design technology, combines the powder characteristics of ZTP, and changes the microstructure and macroscopic properties of ZTP without adding foreign substances through mechanical composite process. To a certain extent, it has improved the preparation defects such as poor taste, unstable properties and poor uniformity in ZTP compound, and preliminarily explored the feasibility of particle design technology in the application of solid preparations of traditional Chinese medicine. It provides reference value for the upgrading of traditional Chinese medicine solid preparation products and the reform of technology. At the same time, it provides new ideas and new methods for the optimization of dosage forms of traditional Chinese medicine preparations rich in volatile oils and extremely unstable properties \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eDeclaration of Competing Interest\u003c/h2\u003e \u003cp\u003eThe authors declared that they have no conflicts of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLile Feng and Mei Wang, Conceptualization, Methodology, Software, and Writing-Original Draft; Yajun Shi, Junbo Zou, and Fei Luan, Data Curation; Xiaofei Zhang and Dongyan Guo, Visualization, Investigation; Bingtao Zhai, Software, Validation; Mei Wang, Writing-Review \u0026amp; Editing; All the authors listed have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThis work was financially supported by the National Natural Science Foundation of China (No. 82274105), the Project of Shaanxi Provincial Department of Science and Technology (No. 2023-YBSF-474), and Science and Technology Innovative Talent Program of Shaanxi University of Chinese Medicine (No. 2024-CXTD-03)\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to Involving business data but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZou, J. et al. Application of particle design technology in field of traditional Chinese medicine powder. \u003cem\u003eChina J. Chin. Mater. Med.\u003c/em\u003e \u003cb\u003e46\u003c/b\u003e, 6011\u0026ndash;6019. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.19540/j.cnki.cjcmm.20210913.301\u003c/span\u003e\u003cspan address=\"10.19540/j.cnki.cjcmm.20210913.301\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen, Z., Wang, J. \u0026amp; Yang, Y. The clinical application and future development of powder in ancient and modern world. \u003cem\u003eLishizhen Med. Mater. Med. Res.\u003c/em\u003e \u003cb\u003e30\u003c/b\u003e, 1720\u0026ndash;1722 (2019). doi:CNKI:SUN:SZGY.0.2019-07-066.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHilden, J. et al. 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Technol.\u003c/em\u003e \u003cb\u003e21\u003c/b\u003e, 6\u0026ndash;11 (2019).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Zhike Taohua Powder, particle design, composite particles, pharmaceutical evaluation, return to prescription","lastPublishedDoi":"10.21203/rs.3.rs-5179870/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5179870/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eTo solve the powder defects that are easy to appear in the preparation process of traditional powder.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe defects of powder preparation were excavated by referring to the technology of material science and pharmaceutical science. The composite particles were prepared and the surface characteristics of the composite particles were evaluated by SEM and IR. Further evaluation of the overall prescription preparation.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe factor causing prescription quality defects was peppermint powder. Preparation of 'core-shell' composite particles to improve the prescription problem. Then the composite particles were returned to the whole prescription, and the powder properties of the prepared composite prescription were improved to a certain extent, the content uniformity was significantly improved, and the material basis of the preparation was not changed before and after modification.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe 'core-shell' composite particles can solve the powder defects in the preparation of traditional powders.\u003c/p\u003e","manuscriptTitle":"Application research on improving the uniformity of Zhike Taohua Powder based on powder modification technology","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-04 09:37:37","doi":"10.21203/rs.3.rs-5179870/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-18T03:12:35+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-17T05:50:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-15T06:40:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"154230396211646498923256326454261474263","date":"2024-11-08T02:27:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144100884072359603926676314251559688809","date":"2024-10-25T13:36:38+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-25T11:36:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-25T11:34:57+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-10-21T04:25:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-17T05:23:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-09-30T10:03:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"71bc042a-16c1-4cb7-a408-f4516f61a2f9","owner":[],"postedDate":"December 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":40374651,"name":"Biological sciences/Drug discovery/Pharmaceutics"},{"id":40374652,"name":"Physical sciences/Materials science"}],"tags":[],"updatedAt":"2024-12-13T04:23:05+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-04 09:37:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5179870","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5179870","identity":"rs-5179870","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}