BIOACTIVE SUBSTANCE-BLOOD PROTEIN CONJUGATE AND STABILIZATION OF A BIOACTIVE SUBSTANCE USING THE SAME

A method for stabilizing a low-molecular-weight bioactive substance and a bioactive substance-blood protein conjugate are provided to modify the low-molecular-weight bioactive substances with short in vivo half-life and low stability by ex vivo conjugating the low-molecular-weight bioactive substance to a blood protein using a reactive group capable of forming a stable bond between the low-molecular-weight bioactive substance and a specific functional group on the blood protein, thereby achieving a stable and efficient in vivo delivery thereof. A method for stabilizing a low-molecular-weight bioactive substance comprises the steps of: (a) reacting a functional group on blood protein, which is selected from the group consisting of hydroxyl group(OH), thiol group(SH), amino group (NH2) and carboxyl group (CO2H), with a reactive group which is capable of forming a stable covalent bond with the functional group, to activate the blood protein and (b) ex vivo reacting the activated blood protein with a low-molecular-weight bioactive substance having molecular weight of less than 100,000 and selected from the group consisting of natural peptides, synthetic peptides, natural hormones, synthetic hormones, and raw materials for drugs, to form a stable covalent bond therebetween, wherein the reactive group is released after the covalent bond is formed. A bioactive substance-blood protein conjugate is characterized in that a stable covalent bond is formed ex vivo between the bioactive substance and the functional group on the blood protein, whereby the stability of the bioactive substance is improved. A composition for treating or preventing a disease on which a bioactive substance has a therapeutic effect comprises an effective amount of the bioactive substance-blood protein conjugate, wherein the disease is diabetes, prostate cancer, endometriosis, or uterus myoma.