Efficacy and Safety of Combination Cream of Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter) Extract), and Saccharide Isomerate After Fractional CO2 Laser Procedure: Split-Face, Double Blinded, Randomized Controlled Trial

Efficacy and Safety of Combination Cream of Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter) Extract), and Saccharide Isomerate After Fractional CO2 Laser Procedure: Split-Face, Double Blinded, Randomized Controlled Trial | 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 Research Article Efficacy and Safety of Combination Cream of Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter) Extract), and Saccharide Isomerate After Fractional CO2 Laser Procedure: Split-Face, Double Blinded, Randomized Controlled Trial Irma Bernadette S. Sitohang, Abraham Arimuko, Lilik Norawati, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7018488/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Oct, 2025 Read the published version in Lasers in Medical Science → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Until now, fractional CO2 laser has been the gold standard for photodamage skin treatment. Topical therapy modalities can accelerate the wound healing process and influence the treatment results. However, no standardized topical therapy exists for subjects after fractional CO2 laser procedures. Purpose: This research aims to determine the efficacy and safety of a cream combination of Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter Extract) and Saccharide Isomerate after fractional CO2 laser treatment. Methods: A split-face, double-blinded, and randomized study was conducted in 2021 with 20 subjects, each given two types of creams, A and B, following fractional CO2 laser procedure. Subjects will apply cream A and cream B to each side of the face according to the randomization results. One of the creams was a moisturizing combination cream with a combination of Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter Extract), and Saccharide Isomerate. Meanwhile, another cream was a placebo. The outcome assessment of this research was carried out subjectively and objectively. The subjective assessment was evaluated using the visual analogue scale (VAS). In contrast, the objective assessment evaluated the degree of erythema using the clinical erythema assessment score (CEA), dermoscopic examination, transepidermal water loss (TEWL) examination with TEWAmeter, and skin capacitance (SCap) with corneometer. This assessment was carried out before the laser procedure, 15 minutes, on the third day, and h the seventh day after the laser procedure. Results: There are 20 subjects recruited into the study, with a split face method, resulting in 40 sample sizes. Significant differences between the experimental and placebo groups were obtained in the assessing of the CEA scale on the third day after the procedure. Meanwhile, on the seventh day after the procedure, significant results were obtained on the TEWL examination with TEWAmeter, SCap with Corneometer, and the degree of erythema using the CEA score. Apart from that, each group had no complaints about adverse events or serious adverse events (SAEs). Conclusion: The combination cream provides good results after the fractional CO2 laser procedure, by reducing the degree of erythema, increasing SCap, and reducing TEWL. Furthermore, this combination cream is safe to use because there were no reports of SAEs. fractional CO2 laser wound healing erythema skin capacitance TEWL Figures Figure 1 Key messages A combination cream containing Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil and Butyrospermum Parkii (Shea Butter) Extract) and Saccharide Isomerate provides a moist environment to accelerate wound healing and reduce erythema after fractional CO2 laser procedure. This split-face, double-blind randomized clinical trial aims to determine the efficacy and safety of a cream combination of Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter Extract) and Saccharide Isomerate versus placebo after fractional CO2 laser treatment within 20 subjects This combination cream has been proven to increase skin hydration, reduce TEWL, and reduce erythema. There are no complaints, adverse events, and serious Adverse Events that arise when using this combination cream, thus this combination cream is safe to use. Introduction A fractional CO2 laser with a wavelength of 10:600 nm is a modality used for wrinkles, large pores, scars, stretch marks, and benign skin tumors. Water is the chromophore target in this laser. However, a fractional CO2 laser has several side effects that can be serious, although rare, including thermal injury, risk of depigmentation and scarring, persistent erythema, and the need to avoid long-term sun exposure. 1 The aim of using moisturizers is to hydrate the skin, maintain suitable skin barriers 2 , relieve symptoms, cause fast and efficient healing in the superficial structures of the epidermis, namely the stratum corneum 3 , and minimize the risk of infection 4 . However, no standardized moisturizer has been used after the fractional CO2 laser procedure. The combination cream used is a moisturizer enriched with Stimu-tex AS™ (Spent Grain Wax, Argania Spinosa Kernel oil, and Butyrospermum Parkii (Shea Butter) Extract) and Saccharide Isomerate. Therefore, the airm of this study is to determine the efficacy and safety of moisturizing cream containing a combination of Stimu-tex AS™ and Saccharide Isomerate after fractional CO2 laser treatment. Material and methods This research has received ethical approval from the Ethics Commission of the Faculty of Medicine, Universitas Indonesia, with ethical number KET-1130/UN2.F1/ETIK/PPM.00.02/2021. All participants were informed about the study procedures and provided written informed consent prior to participation. The study was conducted in accordance with the principles of the Declaration of Helsinki. This trial was registered at ClinicalTrials.gov (registration number: NCT05186246). Subjects This study was conducted on 20 subjects at the Department of Dermatology and Venereology, Presidential-Army Central Hospital Gatot Soebroto, Jakarta, Indonesia, in 2021. The eligibility criteria included women aged 18–60 years who visited the Dermatology and Venereology Clinic for a fractional CO2 laser procedure. The subjects have or will receive a minimum priming containing topical retinoic acid at a concentration of 0.05% tretinoin cream for at least two weeks before the laser procedure, and the subjects understand and agree to participate. Exclusion criteria included: (1) Pregnant women, breastfeeding, or taking oral contraceptives at the time of examination. (2) History of consuming systemic retinoids in the previous 3 months. (3) History of suffering from or undergoing therapy for hormonal or endocrine disorders or other serious illnesses. (4) Currently on immunosuppressant therapy. (5) Non-compliance with treatment. Procedure Each subject was given information about the research and filled out an informed consent form. Each subject underwent anamnesis, physical examination, clinical documentation, visual analogue scale (VAS) assessment, the degree of erythema using the clinical erythema assessment (CEA) scale, dermoscopic examination, and transepidermal water loss (TEWL) examination with a TEWAmeter and skin capacitance (SCap) with a Corneometer at each visit. At the initial visit, subjects were given Retinoic Acid cream 0.05% and instructed to use it for 14 days. On the second visit, the subject underwent fractional CO2 laser treatment on the subject's entire face. After the procedure, the subject's face was compressed with normal saline (0.9% NaCl) for 20 minutes and dried. After that, VAS assessment, the degree of erythema using CEA score, Dermoscopic examination, TEWL examination with TEWAmeter, and SCap examination with Corneometer were assessed. Cream A and B were applied to each side of the subject's face using a split-face study according to the randomization results, as shown in Fig. 1 . One of the creams was a moisturizing combination cream with a combination of Stimu-tex AS™ and Saccharide Isomerate. Meanwhile, the other cream was a placebo. Subjects were provided daily records about the application times of both creams on each side of the face and any occurring side effects. The creams were used twice daily, in the morning and evening. Creams were applied for seven days. This assessment was carried out before the laser procedure, 15 minutes, on the third day, and seventh day after laser procedure. Evaluation Evaluation was carried out by assessing subjectivity with VAS and assessing objectivity by evaluating the degree of erythema using CEA score, dermoscopic examination, TEWL examination with TEWAmeter, and SCap with a corneometer on both sides of each subject's face. The examination is carried out by facial inspection. Evaluation was carried out 15 minutes, 3rd day and 7th day after the fractional CO2 laser procedure. Statistical Analysis Randomization blinding code was kept by the statistical consultant. The masking code is revealed at the completion of the study for statistical analysis. The data obtained was analyzed using the SPSS version 21.0 application. Data were analyzed using the paired T-test and Wilcoxon test in this study. Results The most significant number of subjects were Javanese with 13 people, followed by Sundanese with three subjects, and Batak, Betawi, Minangkabau, and Sundanese-Javanese with one person each. The mean age of the subjects was 42 years (with a range of 29–58 years). Skin aging was found in 14 subjects, with 10 of them also experiencing other skin conditions. Among them, five subjects had acne scars, and four of them also had other skin abnormalities such as depigmentation, melasma, or uneven skin tone. The initial characteristics of the research subjects can be seen in Table 1 . Table 1 Initial Clinical Characteristics of subjects Variable Experimental Group Placebo Group P-value TEWAmeter on Cheek, mean (SD) 71,63 (16,7) 73,63 (14,7) 0,6889 TEWAmeter on Forehead, mean (SD) 69,07 (15,2) 69,43 (14,1) 0,9386 Corneometer on Cheek, mean (SD) 37,46 (9,9) 37,33 (8,8) 0,9662 Corneometer on Forehead, mean (SD) 38,46 (14,1) 43,43 (13,2) 0,2567 Pores 6,59 (1,0) 6,59 (1,0) 1,000 Wrinkles 3,94 (1,2) 3,94 (1,2) 1,000 Pigmentation 6,21 (0,9) 6,21 (0,9) 1,000 Sebum 671,11 (422,7) 671,11 (422,7) 1,000 Note : SD: standard deviation TEWAmeter and Corneometer examinations on the 3rd day after the procedure did not show any significant differences in results between the experimental group and the placebo group ( Table 2 ). On the 7th day after the procedure, there were significant differences between the experimental and placebo groups in the TEWAmeter examination on the cheeks (p = 0.0187) and on the forehead (p = 0.0014). Significant differences on the 7th day were also found in the results of Corneometer examinations on the cheeks (0.0008) and on the forehead (0.0041). There were no significant differences in complaints or adverse events in the two groups. The results of the erythema assessment on the 3rd day and 7th day after the procedure found significant differences, respectively (p = 0.002) and (p = 0.004). On the 7th day, there were more subjects without erythema (grade 0) in the experimental group compared to the placebo group, namely 75%, while there were more subjects with grade 1 erythema in the placebo group than the experimental group, namely 70%. There were no significant differences in the results of examining pores, wrinkles, pigment and sebum between the experimental group and the placebo group at each visit. Table 2 The Examination results on the third and seventh day after the procedure Variable Third day Seventh day Experimental Placebo P - value Experimental Placebo P - value TEWAmeter Cheek, mean (SD) 21,14 (5,4) 23,88 (6,9) 0,0852 15,64 (4,9) 20,08 (1,7) 0,0187 TEWAmeter Forehead, mean (SD) 23,15 (13,8) 30,81 (21,4) 0,0931 18,07 (7,2) 32,83 (19,4) 0,0014 Corneometer Cheek, mean (SD) 26,34 (13,9) 24,83 (12,6) 0,3599 43,47 (9,5) 32,83 (10,4) 0,0008 Corneometer Forehead, mean (SD) 33,38 (16,1) 32,87 (13,5) 0,4566 48,36 (13,8) 36,05 (14,2) 0,0041 Complaint, n (%) 0 17 (85,00) 15 (75,00) 0,695 19 (95,00) 18 (90,00) 1,000 1 3 (15,00) 5 (25,00) 1 (5,00) 2 (10,00) Adverse Events, n (%) 0 13 (65,00) 11 (55,00) 0,749 18 (90,00) 17 (85,00) 1,000 1 5 (25,00) 5 (25,00) 1 (5,00) 2 (10,00) 2 2 (10,00) 4 (20,00) 1 (5,00) 1 (5,00) CEA, n (%) 0 1 (5,00) 1 (5,00) 0,002 15 (75,00) 5 (25,00) 0,004 1 14 (70,00) 4 (20,00) 5 (25,00) 14 (70,00) 2 5 (25,00) 15 (75,00) 0 (0,00) 1 (5,00) Notes : CEA: Clinical Erythema Assessment (0 : Clear, 1 : Almost Clear, 2 : Mild, 3 : Moderate, 4 : Severe), n: number, SD: standard deviation. Discussion Photodamaged skin can be treated with various procedures, including chemical peels. 5 Just like chemical peeling and microneedling, fractional CO2 lasers can be utilized to address photodamage skin, hypertrophic, hypotrophic, or atrophic scars. 6 , 7 However, the fractional CO2 laser procedure is the gold standard for treating photodamaged skin. Fractional CO2 laser procedure is carried out in several stages. The subjects applied a minimum priming containing topical retinoic acid of 0.05% for at least two weeks before the laser procedure. This regimen helps the skin be in optimal condition when the procedure is performed. After the procedure, subjects were instructed to use high-spectrum sunscreen and moisturizer during the day. 3 The results of this therapy are influenced by wound healing process through post-laser therapy. The recommended treatment is moisturizer. Unfortunately, there is no standardized moisturizer which is used as a standard post-laser therapy. A case series was reported by Lestari et al. They used a combination cream of panthenol, madecassoside, and niacinamide after Q-switched Nd: YAG laser therapy. Erythema reduced after day 7, but further research is needed. 8 The combination cream with Stimu-tex AS™ contains unsaturated fatty acids such as linoleic acid (omega-6), oleic acid, stearic acid, and palmitic acid. Linoleic acid has an antiinflammatory effect 9, 10 and can repair damaged skin barriers. 11 In addition, three extracts can relieve epidermal irritation and allergy symptoms and reduce the release of histamine, reducing irritation and itching. 12 Leeyaphan et al. reported that the use of a combination Stimu-tex AS™ is safe and can be used. 13 Butyrospremum Parkii (Shea Butter) Extract has the main content, namely triglycerides, consisting of oleic acid, linoleic acid, stearic acid, and palmitic acid. 14 Other contents are tocopherols, sterols, and phenols. The high tocopherol content in shea butter can increase the regulation of ceramide production 15 and function as an antioxidant. 14 In Shea Butter extract, triterpenes are also found to be moisturizing and anti-aging, 16 anti-inflammatory, 17 antioxidant, 18 – 22 and antitumor effects. 18 , 19 The cinnamate esters contained in it also have anti-inflammatory effects. 18 Besides that, shea butter also has antimicrobial, 19 – 25 antifungal, anti-viral, 26 anti-cancer effects, 27 and at the cellular level, it can inhibit several inflammatory pathways by inhibiting COX-2 and iNOS, downregulating the production of TNF-α, IL-1ꞵ, and IL-12. 28 Elsewedy et al. reported that Shea Butter was safe to use without causing irritation and side effects. 29 Argania Spinosa Kernel (Argan) oil contains 80% unsaturated fatty acids. It contains tocopherols, sterols, polyphenols, squalene, and triterpenes. Topical application can increase skin elasticity. 30 Apart from playing a role in skin elasticity, argan oil can accelerate wound healing and act as an anti-inflammatory. 30 , 31 Argan oil can also increase skin hydration by improving the skin barrier and maintaining water-holding capacity. 32 , 33 No serious adverse events (SAEs) occurred during the study by Boucetta et al., so the argan oil is safe to use. 32 Saccharide Isomerate has several benefits, such as maintaining moisture and increasing the water content in the stratum corneum. 33 , 35 Dewi et al. reported that the adding of 5% Saccharide isomerate to the moisturizer formula can improve and maintain skin hydration. 36 Hartini et al. found that using moisturizer containing Saccharide Isomerate significantly reduces TEWL. 35 Apart from maintaining skin hydration, Saccharide Isomerate can also be used as anti-aging. 36 The results of the corneometer on the third day following the laser procedure showed that corneometer results on the forehead in the experimental group were better than those of the placebo group. However, there was no significant difference between them. In contrast, on the seventh day post-laser treatment, the results for both forehead and cheek corneometer in the experimental group were better than those in the placebo group. Significant results were obtained on the forehead and cheeks with p-values ​​of 0.0041 and 0.0008 respectively. The results showed that the combination cream hydrates the skin more than the placebo cream, with various ingredients that can hydrate the skin, such as Shea Butter, 16 Argan Oil, 32 , 33 and Saccharide Isomerates. 34 – 36 The result on the third day of the TEWAmeter examination, showed improvements inTEWL in both the experimental and the placebo groups, compared with the TEWAmeter results before the laser procedure. The experimental group had better results on the third day after the laser procedure. Unfortunately, there was no significant difference compared with the placebo group. On the seventh day, it was found that the results in the experimental group were excellent because it showed that the skin condition was expected, with an average TEWL of the forehead and cheeks of 18.07 and 15.64, respectively. Meanwhile, in the placebo group, the average forehead TEWL result was worse (32.83), considered a critical skin condition. Thus, the combination cream is more beneficial than the placebo cream. Apart from that, there were also significant results when using the combination cream. These results align with the previous finding of Hartini et al., which was that Saccharide Isomerates significantly reduced TEWL. 35 Evaluation of erythema using CEA score on the third and seventh day showed significant results between the experimental and placebo groups, with p-values ​​of 0.002 and 0.004. On the third day, erythema occurred more frequently in the placebo group. Likewise, on the 7th day, excellent results were obtained in the experimental group, with erythema grade 0 found at 75% of subjects and grade 1 at 25%. Meanwhile, erythema grade 0 was 25% of subjects in the placebo group, and erythema grade 1 was 70%. These outcomes supported the idea that the combination cream has an anti- inflammatory effect obtained from the Grain Spent Wax, Argan Oil, and Shea Butter. 10 , 11 , 17 , 28 The antioxidant effect is also obtained from the shea butter content. 14 , 18 – 19 The excellent improvement in erythema on the seventh day is also one of the benefits of Argan Oil, which accelerates wound healing. 30 , 31 No significant results were found between the experimental and the placebo groups regarding complaints or adverse events on the third or seventh day. The absence of complaints, significant adverse events, and SAEs in this combination cream is by Jirabundansuk et al. that Spent Grain Wax, Argan Oil, and Shea Butter can reduce histamine release. 10 With the absence of complaints, adverse events, and SAEs, it can be concluded that using a combination cream containing Stimu-tex AS™ and Saccharide Isomerate is safe. This study had some strengths. First, randomization and double-blind techniques were used to ensure objective and unbiased results. In addition, at the beginning of the study, an evaluation was carried out regarding the initial characteristics of the subject's skin using anamnesis, physical examination, dermoscopic examination, TEWAmeter, and corneometer. However, further studies are recommended to complete this study such as larger sample size and including various population subjects with Fitzpatrick types I-VI. Conclusion The use of a combination cream containing Stimu-tex AS TM and Saccharide Isomerate provides a moist environment to accelerate wound healing and reduce erythema after fractional CO2 laser procedure. This combination cream has been proven to increase skin hydration, reduce TEWL, and reduce erythema. There are no complaints and Serious Adverse Events (SAEs) that arise when using this combination cream, thus this combination cream is safe to use. Declarations Ethical considerations: This research received ethical approval from the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (Ethical approval number: KET-1130/UN2.F1/ETIK/PPM.00.02/2021. Clinical trial number: This trial was registered at ClinicalTrials.gov (registration number: NCT05186246). Human Ethics and Consent to Participate declarations: This study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants. Acknowledgments: Our deepest gratitude goes to Dr. dr. Wresti Indriatmi, Sp.KK(K), M.Epid for statistical analysis; and dr. Ginindha Izzati Sabila for proofreading the manuscript. Funding: This clinical study received a grant from PT. Taisho Pharmaceutical Indonesia, Tbk (EzerraTM). Conflict of interest: The author reports no conflicts of interest in this work References Petrov A. Efficiency of carbon dioxide fractional laser in skin resurfacing. Open Access Macedonian Journal of Medical Sciences. 2016; 4(2):271-6. Neogenesis. Fractional lasers – fraxel, CO2. [cited 2022 Feb 21]. Available from: https://www.neogenesispro.co.uk/fractional-lasers-fraxel-co2/ Santos-Caetano JP, PharmB RV, Gfeller CF, Cargill M, Mhalingam H. Cosmetic use of three topical moisturizers following glycolic acid facial peels. J Cosmet Dermatol. 2019;00:1-11. Ramsdell WM. Fractional CO2 laser resurfacing complications. Semin Plast Surg. 2012;26:137-40. 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Cite Share Download PDF Status: Published Journal Publication published 24 Oct, 2025 Read the published version in Lasers in Medical Science → Version 1 posted Editorial decision: Revision requested 26 Aug, 2025 Reviews received at journal 25 Aug, 2025 Reviewers agreed at journal 18 Aug, 2025 Reviewers agreed at journal 13 Aug, 2025 Reviews received at journal 10 Aug, 2025 Reviewers agreed at journal 10 Aug, 2025 Reviewers invited by journal 24 Jul, 2025 Editor assigned by journal 24 Jul, 2025 Submission checks completed at journal 11 Jul, 2025 First submitted to journal 01 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7018488","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":490590185,"identity":"6850eeda-8cc6-4da9-863e-eb48374dd41a","order_by":0,"name":"Irma Bernadette S. Sitohang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYBACNhDB2ABmG4AIOQYGHlK0HEhgMCaohQFdS2IDIS180qcTPzDusMk3Zz+88fHHHzbpG46fPfjgA4OdnG4DDofx5W6WYDyTZrmzJ63Y4EBCWu6GM3nJhjMYko3NDuDQwsO7QYKx7bCBwYEcM4kDCYdzNwAZ0jwMBxK34day+Qdj238Dg/NvzH8cSPifDmQQ1LINaMsBA4MbOWZA7x9IADEIarFgPJMM1PKsWOJMWrLhzBtvjA1nGOD2i3wP7+YbjDvsgA5L3vihwsZOnu98juGDDxV2cri0gADzH2SeAlilAW7lWOxtIEX1KBgFo2AUjAQAAAqQXtp4PpTZAAAAAElFTkSuQmCC","orcid":"","institution":"Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital","correspondingAuthor":true,"prefix":"","firstName":"Irma","middleName":"Bernadette S.","lastName":"Sitohang","suffix":""},{"id":490590186,"identity":"badae4a4-6ac9-4a70-bd48-db6b5c0cdb62","order_by":1,"name":"Abraham Arimuko","email":"","orcid":"","institution":"Presidential-Army Central Hospital Gatot Soebroto","correspondingAuthor":false,"prefix":"","firstName":"Abraham","middleName":"","lastName":"Arimuko","suffix":""},{"id":490590187,"identity":"d69f5df9-394c-4052-acff-14d8e2c8e8a6","order_by":2,"name":"Lilik Norawati","email":"","orcid":"","institution":"Presidential-Army Central Hospital Gatot Soebroto","correspondingAuthor":false,"prefix":"","firstName":"Lilik","middleName":"","lastName":"Norawati","suffix":""},{"id":490590188,"identity":"b448d429-cfcf-4293-9cc7-8de958e85037","order_by":3,"name":"Rita Maria","email":"","orcid":"","institution":"Presidential-Army Central Hospital Gatot Soebroto","correspondingAuthor":false,"prefix":"","firstName":"Rita","middleName":"","lastName":"Maria","suffix":""},{"id":490590189,"identity":"b193ad4f-be37-4804-b3db-2b88a292ac62","order_by":4,"name":"Cyntia Yulyana","email":"","orcid":"","institution":"Presidential-Army Central Hospital Gatot Soebroto","correspondingAuthor":false,"prefix":"","firstName":"Cyntia","middleName":"","lastName":"Yulyana","suffix":""},{"id":490590190,"identity":"afd505a8-cafe-40b2-9c8b-f273db62bc1c","order_by":5,"name":"Randy Satria Nugraha","email":"","orcid":"","institution":"Presidential-Army Central Hospital Gatot Soebroto","correspondingAuthor":false,"prefix":"","firstName":"Randy","middleName":"Satria","lastName":"Nugraha","suffix":""},{"id":490590191,"identity":"93777dfa-c008-4cd4-8eba-3398ff167345","order_by":6,"name":"Vashty Amanda","email":"","orcid":"","institution":"Presidential-Army Central Hospital Gatot Soebroto","correspondingAuthor":false,"prefix":"","firstName":"Vashty","middleName":"","lastName":"Amanda","suffix":""},{"id":490590192,"identity":"b7292984-8805-43ab-a846-ffd7cca4519e","order_by":7,"name":"Arsy Indrafatina","email":"","orcid":"","institution":"Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital","correspondingAuthor":false,"prefix":"","firstName":"Arsy","middleName":"","lastName":"Indrafatina","suffix":""},{"id":490590194,"identity":"28f2e26c-108c-4b01-85f8-f3f1ccc05a59","order_by":8,"name":"Inasa Amalia","email":"","orcid":"","institution":"Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital","correspondingAuthor":false,"prefix":"","firstName":"Inasa","middleName":"","lastName":"Amalia","suffix":""}],"badges":[],"createdAt":"2025-07-01 09:23:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7018488/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7018488/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10103-025-04703-5","type":"published","date":"2025-10-24T16:16:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87709663,"identity":"db0e195f-cdab-430f-9abd-0303151f39f1","added_by":"auto","created_at":"2025-07-28 08:27:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":62396,"visible":true,"origin":"","legend":"\u003cp\u003eClinical trial flowchart\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7018488/v1/9c7c5e5c0ac6dcb27736b457.png"},{"id":94490593,"identity":"4953da17-4614-454d-a8d8-71a94d6811a9","added_by":"auto","created_at":"2025-10-27 17:12:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":755086,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7018488/v1/43758ee4-d622-4edc-9932-431e1046dc6a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and Safety of Combination Cream of Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter) Extract), and Saccharide Isomerate After Fractional CO2 Laser Procedure: Split-Face, Double Blinded, Randomized Controlled Trial","fulltext":[{"header":"Key messages","content":"\u003cul\u003e\n \u003cli\u003eA combination cream containing Stimu-tex AS\u003csup\u003eTM\u003c/sup\u003e (Spent Grain Wax, Argania Spinosa Kernel Oil and Butyrospermum Parkii (Shea Butter) Extract) and Saccharide Isomerate provides a moist environment to accelerate wound healing and reduce erythema after fractional CO2 laser procedure.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eThis split-face, double-blind randomized clinical trial aims to determine the efficacy and safety of a cream combination of Stimu-tex AS\u003csup\u003eTM\u003c/sup\u003e (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter Extract) and Saccharide Isomerate versus placebo after fractional CO2 laser treatment within 20 subjects\u003c/li\u003e\n \u003cli\u003eThis combination cream has been proven to increase skin hydration, reduce TEWL, and reduce erythema. There are no complaints, adverse events, and serious Adverse Events that arise when using this combination cream, thus this combination cream is safe to use.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eA fractional CO2 laser with a wavelength of 10:600 nm is a modality used for wrinkles, large pores, scars, stretch marks, and benign skin tumors. Water is the chromophore target in this laser. However, a fractional CO2 laser has several side effects that can be serious, although rare, including thermal injury, risk of depigmentation and scarring, persistent erythema, and the need to avoid long-term sun exposure.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe aim of using moisturizers is to hydrate the skin, maintain suitable skin barriers\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, relieve symptoms, cause fast and efficient healing in the superficial structures of the epidermis, namely the stratum corneum\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e, and minimize the risk of infection\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. However, no standardized moisturizer has been used after the fractional CO2 laser procedure. The combination cream used is a moisturizer enriched with Stimu-tex AS\u0026trade; (Spent Grain Wax, Argania Spinosa Kernel oil, and Butyrospermum Parkii (Shea Butter) Extract) and Saccharide Isomerate.\u003c/p\u003e\u003cp\u003eTherefore, the airm of this study is to determine the efficacy and safety of moisturizing cream containing a combination of Stimu-tex AS\u0026trade; and Saccharide Isomerate after fractional CO2 laser treatment.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003e This research has received ethical approval from the Ethics Commission of the Faculty of Medicine, Universitas Indonesia, with ethical number KET-1130/UN2.F1/ETIK/PPM.00.02/2021. All participants were informed about the study procedures and provided written informed consent prior to participation. The study was conducted in accordance with the principles of the Declaration of Helsinki. This trial was registered at ClinicalTrials.gov (registration number: NCT05186246).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSubjects\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study was conducted on 20 subjects at the Department of Dermatology and Venereology, Presidential-Army Central Hospital Gatot Soebroto, Jakarta, Indonesia, in 2021. The eligibility criteria included women aged 18\u0026ndash;60 years who visited the Dermatology and Venereology Clinic for a fractional CO2 laser procedure. The subjects have or will receive a minimum priming containing topical retinoic acid at a concentration of 0.05% tretinoin cream for at least two weeks before the laser procedure, and the subjects understand and agree to participate.\u003c/p\u003e\u003cp\u003eExclusion criteria included: (1) Pregnant women, breastfeeding, or taking oral contraceptives at the time of examination. (2) History of consuming systemic retinoids in the previous 3 months. (3) History of suffering from or undergoing therapy for hormonal or endocrine disorders or other serious illnesses. (4) Currently on immunosuppressant therapy. (5) Non-compliance with treatment.\u003c/p\u003e\u003cp\u003e\u003cb\u003eProcedure\u003c/b\u003e\u003c/p\u003e\u003cp\u003e Each subject was given information about the research and filled out an informed consent form. Each subject underwent anamnesis, physical examination, clinical documentation, visual analogue scale (VAS) assessment, the degree of erythema using the clinical erythema assessment (CEA) scale, dermoscopic examination, and transepidermal water loss (TEWL) examination with a TEWAmeter and skin capacitance (SCap) with a Corneometer at each visit. At the initial visit, subjects were given Retinoic Acid cream 0.05% and instructed to use it for 14 days. On the second visit, the subject underwent fractional CO2 laser treatment on the subject's entire face. After the procedure, the subject's face was compressed with normal saline (0.9% NaCl) for 20 minutes and dried. After that, VAS assessment, the degree of erythema using CEA score, Dermoscopic examination, TEWL examination with TEWAmeter, and SCap examination with Corneometer were assessed. Cream A and B were applied to each side of the subject's face using a split-face study according to the randomization results, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. One of the creams was a moisturizing combination cream with a combination of Stimu-tex AS\u0026trade; and Saccharide Isomerate.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMeanwhile, the other cream was a placebo. Subjects were provided daily records about the application times of both creams on each side of the face and any occurring side effects. The creams were used twice daily, in the morning and evening. Creams were applied for seven days. This assessment was carried out before the laser procedure, 15 minutes, on the third day, and seventh day after laser procedure.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEvaluation\u003c/b\u003e\u003c/p\u003e\u003cp\u003eEvaluation was carried out by assessing subjectivity with VAS and assessing objectivity by evaluating the degree of erythema using CEA score, dermoscopic examination, TEWL examination with TEWAmeter, and SCap with a corneometer on both sides of each subject's face. The examination is carried out by facial inspection. Evaluation was carried out 15 minutes, 3rd day and 7th day after the fractional CO2 laser procedure.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eRandomization blinding code was kept by the statistical consultant. The masking code is revealed at the completion of the study for statistical analysis. The data obtained was analyzed using the SPSS version 21.0 application. Data were analyzed using the paired T-test and Wilcoxon test in this study.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe most significant number of subjects were Javanese with 13 people, followed by Sundanese with three subjects, and Batak, Betawi, Minangkabau, and Sundanese-Javanese with one person each. The mean age of the subjects was 42 years (with a range of 29\u0026ndash;58 years). Skin aging was found in 14 subjects, with 10 of them also experiencing other skin conditions. Among them, five subjects had acne scars, and four of them also had other skin abnormalities such as depigmentation, melasma, or uneven skin tone. The initial characteristics of the research subjects can be seen in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eInitial Clinical Characteristics of subjects\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eExperimental Group\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePlacebo Group\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTEWAmeter on Cheek, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71,63 (16,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73,63 (14,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,6889\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTEWAmeter on Forehead, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69,07 (15,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69,43 (14,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,9386\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCorneometer on Cheek, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37,46 (9,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37,33 (8,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,9662\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCorneometer on Forehead, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38,46 (14,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43,43 (13,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,2567\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePores\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,59 (1,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,59 (1,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWrinkles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,94 (1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,94 (1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePigmentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,21 (0,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,21 (0,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSebum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e671,11 (422,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e671,11 (422,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003cstrong\u003eNote\u003c/strong\u003e: SD: standard deviation\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTEWAmeter and Corneometer examinations on the 3rd day after the procedure did not show any significant differences in results between the experimental group and the placebo group \u003cstrong\u003e(\u003c/strong\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cstrong\u003e).\u003c/strong\u003e On the 7th day after the procedure, there were significant differences between the experimental and placebo groups in the TEWAmeter examination on the cheeks (p\u0026thinsp;=\u0026thinsp;0.0187) and on the forehead (p\u0026thinsp;=\u0026thinsp;0.0014). Significant differences on the 7th day were also found in the results of Corneometer examinations on the cheeks (0.0008) and on the forehead (0.0041). There were no significant differences in complaints or adverse events in the two groups. The results of the erythema assessment on the 3rd day and 7th day after the procedure found significant differences, respectively (p\u0026thinsp;=\u0026thinsp;0.002) and (p\u0026thinsp;=\u0026thinsp;0.004). On the 7th day, there were more subjects without erythema (grade 0) in the experimental group compared to the placebo group, namely 75%, while there were more subjects with grade 1 erythema in the placebo group than the experimental group, namely 70%. There were no significant differences in the results of examining pores, wrinkles, pigment and sebum between the experimental group and the placebo group at each visit.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\" class=\"fr-table-selection-hover\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe Examination results on the third and seventh day after the procedure\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eThird day\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eSeventh day\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eExperimental\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e- value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eExperimental\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e- value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTEWAmeter Cheek, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21,14 (5,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23,88 (6,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0,0852\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15,64 (4,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20,08 (1,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,0187\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTEWAmeter Forehead, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23,15 (13,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30,81 (21,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0,0931\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18,07 (7,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32,83 (19,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,0014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCorneometer Cheek, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26,34 (13,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24,83 (12,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0,3599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43,47 (9,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32,83 (10,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,0008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCorneometer Forehead, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33,38 (16,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32,87 (13,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0,4566\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48,36 (13,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36,05 (14,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,0041\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eComplaint, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (85,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (75,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0,695\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (95,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (90,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (15,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (25,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eAdverse Events, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (65,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (55,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e0,749\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (90,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (85,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e1,000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (25,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (25,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (20,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eCEA, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (75,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (25,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (70,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (20,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (25,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (70,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (25,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (75,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5,00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e\u003cstrong\u003eNotes\u003c/strong\u003e: CEA: Clinical Erythema Assessment (0 : Clear, 1 : Almost Clear, 2 : Mild, 3 : Moderate, 4 : Severe), n: number, SD: standard deviation.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePhotodamaged skin can be treated with various procedures, including chemical peels.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Just like chemical peeling and microneedling, fractional CO2 lasers can be utilized to address photodamage skin, hypertrophic, hypotrophic, or atrophic scars.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e However, the fractional CO2 laser procedure is the gold standard for treating photodamaged skin. Fractional CO2 laser procedure is carried out in several stages. The subjects applied a minimum priming containing topical retinoic acid of 0.05% for at least two weeks before the laser procedure. This regimen helps the skin be in optimal condition when the procedure is performed. After the procedure, subjects were instructed to use high-spectrum sunscreen and moisturizer during the day.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe results of this therapy are influenced by wound healing process through post-laser therapy. The recommended treatment is moisturizer. Unfortunately, there is no standardized moisturizer which is used as a standard post-laser therapy. A case series was reported by Lestari et al. They used a combination cream of panthenol, madecassoside, and niacinamide after Q-switched Nd: YAG laser therapy. Erythema reduced after day 7, but further research is needed.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe combination cream with Stimu-tex AS\u0026trade; contains unsaturated fatty acids such as linoleic acid (omega-6), oleic acid, stearic acid, and palmitic acid. Linoleic acid has an antiinflammatory effect\u003csup\u003e9,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e and can repair damaged skin barriers.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e In addition, three extracts can relieve epidermal irritation and allergy symptoms and reduce the release of histamine, reducing irritation and itching.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Leeyaphan et al. reported that the use of a combination Stimu-tex AS\u0026trade; is safe and can be used.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eButyrospremum Parkii (Shea Butter) Extract has the main content, namely triglycerides, consisting of oleic acid, linoleic acid, stearic acid, and palmitic acid.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Other contents are tocopherols, sterols, and phenols. The high tocopherol content in shea butter can increase the regulation of ceramide production\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e and function as an antioxidant.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e In Shea Butter extract, triterpenes are also found to be moisturizing and anti-aging,\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e anti-inflammatory,\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e antioxidant,\u003csup\u003e\u003cspan additionalcitationids=\"CR19 CR20 CR21\" citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e and antitumor effects.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e The cinnamate esters contained in it also have anti-inflammatory effects.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Besides that, shea butter also has antimicrobial,\u003csup\u003e\u003cspan additionalcitationids=\"CR20 CR21 CR22 CR23 CR24\" citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e antifungal, anti-viral,\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e anti-cancer effects,\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e and at the cellular level, it can inhibit several inflammatory pathways by inhibiting COX-2 and iNOS, downregulating the production of TNF-α, IL-1ꞵ, and IL-12.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Elsewedy et al. reported that Shea Butter was safe to use without causing irritation and side effects.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eArgania Spinosa Kernel (Argan) oil contains 80% unsaturated fatty acids. It contains tocopherols, sterols, polyphenols, squalene, and triterpenes. Topical application can increase skin elasticity.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Apart from playing a role in skin elasticity, argan oil can accelerate wound healing and act as an anti-inflammatory.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Argan oil can also increase skin hydration by improving the skin barrier and maintaining water-holding capacity.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e No serious adverse events (SAEs) occurred during the study by Boucetta et al., so the argan oil is safe to use.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eSaccharide Isomerate has several benefits, such as maintaining moisture and increasing the water content in the stratum corneum.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e Dewi et al. reported that the adding of 5% Saccharide isomerate to the moisturizer formula can improve and maintain skin hydration.\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e Hartini et al. found that using moisturizer containing Saccharide Isomerate significantly reduces TEWL.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e Apart from maintaining skin hydration, Saccharide Isomerate can also be used as anti-aging.\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe results of the corneometer on the third day following the laser procedure showed that corneometer results on the forehead in the experimental group were better than those of the placebo group. However, there was no significant difference between them. In contrast, on the seventh day post-laser treatment, the results for both forehead and cheek corneometer in the experimental group were better than those in the placebo group. Significant results were obtained on the forehead and cheeks with \u003cem\u003ep-values\u003c/em\u003e ​​of 0.0041 and 0.0008 respectively. The results showed that the combination cream hydrates the skin more than the placebo cream, with various ingredients that can hydrate the skin, such as Shea Butter,\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Argan Oil,\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e and Saccharide Isomerates.\u003csup\u003e\u003cspan additionalcitationids=\"CR35\" citationid=\"CR33\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe result on the third day of the TEWAmeter examination, showed improvements inTEWL in both the experimental and the placebo groups, compared with the TEWAmeter results before the laser procedure. The experimental group had better results on the third day after the laser procedure. Unfortunately, there was no significant difference compared with the placebo group. On the seventh day, it was found that the results in the experimental group were excellent because it showed that the skin condition was expected, with an average TEWL of the forehead and cheeks of 18.07 and 15.64, respectively. Meanwhile, in the placebo group, the average forehead TEWL result was worse (32.83), considered a critical skin condition. Thus, the combination cream is more beneficial than the placebo cream. Apart from that, there were also significant results when using the combination cream. These results align with the previous finding of Hartini et al., which was that Saccharide Isomerates significantly reduced TEWL.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eEvaluation of erythema using CEA score on the third and seventh day showed significant results between the experimental and placebo groups, with \u003cem\u003ep-values\u003c/em\u003e ​​of 0.002 and 0.004. On the third day, erythema occurred more frequently in the placebo group. Likewise, on the 7th day, excellent results were obtained in the experimental group, with erythema grade 0 found at 75% of subjects and grade 1 at 25%. Meanwhile, erythema grade 0 was 25% of subjects in the placebo group, and erythema grade 1 was 70%. These outcomes supported the idea that the combination cream has an anti- inflammatory effect obtained from the Grain Spent Wax, Argan Oil, and Shea Butter.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e The antioxidant effect is also obtained from the shea butter content.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e The excellent improvement in erythema on the seventh day is also one of the benefits of Argan Oil, which accelerates wound healing.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNo significant results were found between the experimental and the placebo groups regarding complaints or adverse events on the third or seventh day. The absence of complaints, significant adverse events, and SAEs in this combination cream is by Jirabundansuk et al. that Spent Grain Wax, Argan Oil, and Shea Butter can reduce histamine release.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e With the absence of complaints, adverse events, and SAEs, it can be concluded that using a combination cream containing Stimu-tex AS\u0026trade; and Saccharide Isomerate is safe.\u003c/p\u003e\u003cp\u003eThis study had some strengths. First, randomization and double-blind techniques were used to ensure objective and unbiased results. In addition, at the beginning of the study, an evaluation was carried out regarding the initial characteristics of the subject's skin using anamnesis, physical examination, dermoscopic examination, TEWAmeter, and corneometer. However, further studies are recommended to complete this study such as larger sample size and including various population subjects with Fitzpatrick types I-VI.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe use of a combination cream containing Stimu-tex AS\u003csup\u003eTM\u003c/sup\u003e and Saccharide Isomerate provides a moist environment to accelerate wound healing and reduce erythema after fractional CO2 laser procedure. This combination cream has been proven to increase skin hydration, reduce TEWL, and reduce erythema. There are no complaints and Serious Adverse Events (SAEs) that arise when using this combination cream, thus this combination cream is safe to use.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical considerations:\u0026nbsp;\u003c/strong\u003eThis research received ethical approval from the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (Ethical approval number: KET-1130/UN2.F1/ETIK/PPM.00.02/2021.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e This trial was registered at ClinicalTrials.gov (registration number: NCT05186246).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations:\u003c/strong\u003e\u0026nbsp;This study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments: \u003c/strong\u003eOur deepest gratitude goes to Dr. dr. Wresti Indriatmi, Sp.KK(K), M.Epid for statistical analysis; and dr. Ginindha Izzati Sabila for proofreading the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis clinical study received a grant from PT. Taisho Pharmaceutical Indonesia, Tbk (EzerraTM).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe author reports no conflicts of interest in this work\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003ePetrov A. Efficiency of carbon dioxide fractional laser in skin resurfacing. Open Access Macedonian Journal of Medical Sciences. 2016; 4(2):271-6.\u003c/li\u003e\n \u003cli\u003eNeogenesis. Fractional lasers \u0026ndash; fraxel, CO2. [cited 2022 Feb 21]. Available from: https://www.neogenesispro.co.uk/fractional-lasers-fraxel-co2/\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/li\u003e\n \u003cli\u003eSantos-Caetano JP, PharmB RV, Gfeller CF, Cargill M, Mhalingam H. Cosmetic use of three topical moisturizers following glycolic acid facial peels. J Cosmet Dermatol. 2019;00:1-11.\u003c/li\u003e\n \u003cli\u003eRamsdell WM. Fractional CO2 laser resurfacing complications. Semin Plast Surg. 2012;26:137-40.\u003c/li\u003e\n \u003cli\u003eSitohang IB, Rahmayunita G, Hosfiar VA, Ninditya S, Augustin M. Effectiveness of water as the neutralising agent for glycolic acid peels in skin phototypes IV-V. Australas J Dermatol. 2021 May;62(2):e212-e216. doi: 10.1111/ajd.13486.\u003c/li\u003e\n \u003cli\u003eSitohang IB, Sirait SAP, Suryanegara J. Microneedling in the treatment of atrophic scars: A systematic review of randomised controlled trials. Int Wound J. 2021 Oct;18(5):577-585. doi: 10.1111/iwj.13559.\u003c/li\u003e\n \u003cli\u003eSitohang IB, Sirait SA, Safira FD. Fractional carbon dioxide laser for treating hypertrophic scars: A systematic review of randomised trials. Australas J Dermatol. 2022 Feb;63(1):27-35. doi: 10.1111/ajd.13730.\u003c/li\u003e\n \u003cli\u003eLestari AA, Adistri K, Hopkop T, Sitohang IB. Combination of panthenol, madecassoside and niacinamide in multi-lamellar emulsion as postprocedural laser treatment. \u003cem\u003eJournal of Pakistan Association of Dermatologists\u003c/em\u003e.2023;\u003cstrong\u003e33(2)\u003c/strong\u003e:706-710.\u003c/li\u003e\n \u003cli\u003eCalder PC. Polyunsaturated fatty acids and inflammation. Biochem Soc Trans. 2005;33:423-7.\u003c/li\u003e\n \u003cli\u003eJirabundansuk P, Ophaswongse S, Udompataikul M. Comparative trial of moisturizer containing spent grain wax, Butyrospermum parkii extract, Argania spinosa kernel oil vs. 1% hydrocortisone cream in the treatment of childhood atopic dermatitis. J Med Assoc Thai. 2014;97(8):820-6.\u003c/li\u003e\n \u003cli\u003eElias PM, Brown BE, Ziboh VA. The permeability barrier in essential fatty acid deficiency: evidence for a direct role for linoleic acid in barrier function. J Invest Dermatol. 1980 Apr;74(4):230-3. doi: 10.1111/1523-1747.ep12541775.\u003c/li\u003e\n \u003cli\u003eHon KL, Wang SS, Pong NH, Leung TF. The ideal moisturizer: a survey of parental expectations and practice in childhood-onset eczema. J Dermatologist Treat. 2013;24:7\u0026ndash;12. doi: 10.3109/09546634.2012.672713.\u003c/li\u003e\n \u003cli\u003eLeeyaphan C, Varothai S, Trakanwittayarak S, et al. A randomized controlled trial to compare the effectiveness and safety of adsorbent lotion containing tapioca starch, spent grain wax, Butyrospermum parkii extract, argania spinosa kernel oil, aloe barbadensis, rosehip oil, and allantoin with a low-potency topical corticosteroid in the treatment of intertrigo . J Cosmet Dermatol. 2022;21(2):679-88. doi:10.1111/jocd.14125.\u003c/li\u003e\n \u003cli\u003eMaranz S, Wiesman Z. Influence of climate on the tocopherol content of shea butter. J. Agric. Food Chem. 2004;52:2934\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eLin TK, Zhong L, Santiago JL. Anti-inflammatory and skin barrier repair effects of topical application of some plant oils. Int J Mol Sci. 2017;19(1):70.\u003c/li\u003e\n \u003cli\u003eAlander J. Shea butter-a multifunctional ingredient for food and cosmetics. Lipid Technol 2004;16:202-5.\u003c/li\u003e\n \u003cli\u003eLim D, Bae S, Oh T. Anti-inflammatory effect of shea butter extracts in canine keratinocytes. Journal of Veterinary Clinics. 2021;83:27\u0026ndash;31.\u003c/li\u003e\n \u003cli\u003eAkihisa T, Kojima N, Kikuchi T, Yasukawa K, Tokuda H, Masters T, et al. Anti-inflammatory and chemopreventive effects of triterpene cinnamates and acetates from shea fat. J Oleo Sci. 2010;59:273-80.\u003c/li\u003e\n \u003cli\u003eKao JH, Lin SH, Lai CF, Lin YC, Kong ZL, Wong CS. Shea nut oil Triterpene concentrate attenuates knee osteoarthritis development in rats: evidence from knee joint histology. PLOS One. 2016;11(9):e0162022.\u003c/li\u003e\n \u003cli\u003eFoyet HS, Tsala DE, Bodo JZ, Carine AN, Heroyne LT, Oben EK. Anti-inflammatory and anti-arthritic activity of a methanol extract from Vitellaria paradoxa stem bark. Pharmacognosy Res. 2015;7:367.\u003c/li\u003e\n \u003cli\u003eOlasunkanmi OO, Akinpelu DA, Adeniyi PO, Ajayi OF, Omololu-Aso J, Olorunmola FO. Investigations into antibacterial, phytochemical and antioxidant properties of Vitellaria paradoxa (Gaertn.) Stem Bark Extracts. Journal of Pharmaceutical Research International. 2018;20(5):1\u0026ndash;17.\u003c/li\u003e\n \u003cli\u003eIgbeneghu OA. The antimicrobial assessment of some Nigerian herbal soaps. Afr J Tradit Complement Altern Med. 2013;10(6):513-8.\u003c/li\u003e\n \u003cli\u003eOjo O, Kengne MH, Fotsing MC, Mutlane E.M, Ndinteh DT. Traditional uses, phytochemistry, pharmacology and other potential applications of Vitellaria paradoxa Gaertn. (Sapotaceae): a review. Arabian Journal of Chemistry. 2021;14:103213.\u003c/li\u003e\n \u003cli\u003eAjijolakewu KA, Awarun FJ. Comparative antibacterial efficacy of Vitellaria paradoxa (Shea Butter Tree) extracts against some clinical bacterial isolates. \u003cem\u003eNotulae Scientia Biologicae\u003c/em\u003e. 2015;7(3):264\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eWada NM, Muhammad MI, Garba USA, Ghazali HM. Antibacterial activity of Vitellaria paradoxa seed oil extract and honey against bacterial isolates from wound infection. \u003cem\u003eInternational Journal of Biological, Physical and Chemical Studies\u003c/em\u003e. 2019;1:16\u0026ndash;21.\u003c/li\u003e\n \u003cli\u003eBoyejo I, Azeez S, Owolabi A, Issah O. Antifungal and phytochemical screening of extract from Vitellaria paradoxa (shea butter tree) leaves, barks and roots on Dermatophytes. International Journal of Scientific and Research Publications. 2019;9:90129.\u003c/li\u003e\n \u003cli\u003eZhang J, Li D, Lv Q, Ye F, Jing X, Masters ET, et al. Compositions and melanogenesis inhibitory activities of the extracts of defatted shea (Vitellaria paradoxa) kernels from seven African countries. Journal of Food Composition and Analysis. 2018;70:89\u0026ndash;97.\u003c/li\u003e\n \u003cli\u003eVerma N, Chakrabarti R, Das RH, Gautam HK. Anti-inflammatory effects of shea butter through inhibition of iNOS, COX-2, and cytokines via the Nf-\u0026kappa;B pathway in LPS-activated J774 macrophage cells. J Complement Integr Med. 2012;9:1-11.\u003c/li\u003e\n \u003cli\u003eElsewedy HS, Shehata TM, Soliman WE. Shea butter potentiates the anti-bacterial activity of fusidic acid incorporated into solid lipid nanoparticles. Polymers (Basel). 2022 Jun 16;14(12):2436. doi: 10.3390/polym14122436.\u003c/li\u003e\n \u003cli\u003eBoucetta KQ, Charrouf Z, Aguenaou H, Derouiche A, Bensouda Y. The effect of dietary and/or cosmetic argan oil on postmenopausal skin elasticity. Clin Interv Aging. 2015;10:339\u0026ndash;49.\u003c/li\u003e\n \u003cli\u003eAvsar U, Halici Z, Akpinar E, Yayla M, Avsar U, Aaron U, et al. The effects of argan oil in second-degree burn wound healing in rats. Ostomy Wound Management. 2016;62:26\u0026ndash;34.\u003c/li\u003e\n \u003cli\u003eTichota DM, Silva AC, Sousa Lobo JM, Amaral MH. Design, characterization, and clinical evaluation of argan oil nanostructured lipid carriers to improve skin hydration. Int J Nanomedicine. 2014 Aug 11;9:3855-64. doi: 10.2147/IJN.S64008.\u003c/li\u003e\n \u003cli\u003eVlorensia, Hartini H, Abdullah H, Martinus AR, Ikhtiari R. The effect of a moisturizing cream with saccharide isomerates and ceramide on increasing skin hydration. SCITEPRESS. 2019:428-35.\u003c/li\u003e\n \u003cli\u003eBoucetta KQ, Charrouf Z, Derouiche A, Rahali Y, Bensouda Y. Skin hydration in postmenopausal women: argan oil benefits with oral and/or topical use. Prz Menopauzalny. 2014 Oct;13(5):280-8. doi: 10.5114/pm.2014.46470.\u003c/li\u003e\n \u003cli\u003eHartini H, Vlorensia, Abdullah H, Martinus AR, Ikhtiari R. The effect of a moisturizing cream containing saccharide isomerates and ceramide on reducing transepidermal water loss in eczema. SCITEPRESS. 2019:411-7.\u003c/li\u003e\n \u003cli\u003eDewi DA, Pangkahila W. Additional of 5% saccharide isomerates in moisturizing formulation increases skin hydration higher than regular moisturizers. Eduvest Journal of Universal Studies. 2022 Aug;2(8):1537-49.\u003c/li\u003e\n\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":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"fractional CO2 laser, wound healing, erythema, skin capacitance, TEWL","lastPublishedDoi":"10.21203/rs.3.rs-7018488/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7018488/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eUntil now, fractional CO2 laser has been the gold standard for photodamage skin treatment. Topical therapy modalities can accelerate the wound healing process and influence the treatment results. However, no standardized topical therapy exists for subjects after fractional CO2 laser procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eThis research aims to determine the efficacy and safety of a cream combination of Stimu-tex AS\u003csup\u003eTM\u003c/sup\u003e (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter Extract) and Saccharide Isomerate after fractional CO2 laser treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA split-face, double-blinded, and randomized study was conducted in 2021 with 20 subjects, each given two types of creams, A and B, following fractional CO2 laser procedure. Subjects will apply cream A and cream B to each side of the face according to the randomization results. One of the creams was a moisturizing combination cream with a combination of Stimu-tex AS\u003csup\u003eTM\u003c/sup\u003e (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter Extract), and Saccharide Isomerate. Meanwhile, another cream was a placebo. The outcome assessment of this research was carried out subjectively and objectively. The subjective assessment was evaluated using the visual analogue scale (VAS). In contrast, the objective assessment evaluated the degree of erythema using the clinical erythema assessment score (CEA), dermoscopic examination, transepidermal water loss (TEWL) examination with TEWAmeter, and skin capacitance (SCap) with corneometer. This assessment was carried out before the laser procedure, 15 minutes, on the third day, and \u003csup\u003eh\u003c/sup\u003e the seventh day after the laser procedure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThere are 20 subjects recruited into the study, with a split face method, resulting in 40 sample sizes. Significant differences between the experimental and placebo groups were obtained in the assessing of the CEA scale on the third day after the procedure. Meanwhile, on the seventh day after the procedure, significant results were obtained on the TEWL examination with TEWAmeter, SCap with Corneometer, and the degree of erythema using the CEA score. Apart from that, each group had no complaints about adverse events or serious adverse events\u0026nbsp;(SAEs).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe combination cream provides good results after the fractional CO2 laser procedure, by reducing the degree of erythema, increasing SCap, and reducing TEWL. Furthermore, this combination cream is safe to use because there were no reports of SAEs.\u003c/p\u003e","manuscriptTitle":"Efficacy and Safety of Combination Cream of Stimu-tex AS TM (Spent Grain Wax, Argania Spinosa Kernel Oil, Butyrospermum Parkii (Shea Butter) Extract), and Saccharide Isomerate After Fractional CO2 Laser Procedure: Split-Face, Double Blinded, Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-28 08:27:47","doi":"10.21203/rs.3.rs-7018488/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-26T17:14:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-25T06:57:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"56634940204988491859171240275570983638","date":"2025-08-18T09:04:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"68377290737201297246649611100406505977","date":"2025-08-14T00:50:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-10T23:20:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"267887417517897798648413415561442029766","date":"2025-08-10T22:45:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-24T21:48:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-24T15:24:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-11T05:46:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"Lasers in Medical Science","date":"2025-07-01T09:09:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e681eed8-549b-4de9-bcb0-6c015ae9947a","owner":[],"postedDate":"July 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:34:13+00:00","versionOfRecord":{"articleIdentity":"rs-7018488","link":"https://doi.org/10.1007/s10103-025-04703-5","journal":{"identity":"lasers-in-medical-science","isVorOnly":false,"title":"Lasers in Medical Science"},"publishedOn":"2025-10-24 16:16:42","publishedOnDateReadable":"October 24th, 2025"},"versionCreatedAt":"2025-07-28 08:27:47","video":"","vorDoi":"10.1007/s10103-025-04703-5","vorDoiUrl":"https://doi.org/10.1007/s10103-025-04703-5","workflowStages":[]},"version":"v1","identity":"rs-7018488","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7018488","identity":"rs-7018488","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}