生物降解高分子复合材料设计及多肽与蛋白药物控释体系

With the development of gene engineering and life science, many new.polypeptide/protein drugs are emerged for medical include family planning.application. These drugs have many merits that the traditional small molecular drugs lacks. But the polypeptide/protein drugs are unstable, that limit the wide application of these drugs. Drug delivery systems using polymer carrier/matrix is the effectual.way to improve the stability the drugs. The bioavailability can also be improved. So,many studies are focus on the preparation of Drug delivery systems for polypeptide/proteins..Many ways such as improve the preparation method, modification of polymers,synthesis of new hydrophilic monomers, etc. were investigated in this project to improve the loading rate, stability and bioavailability of the polypeptide/protein drugs.The impotent results were listed as following:1. Block copolymer of PCL/PLA was synthesized and the biodegradability in vitra and in vivo were studied. The results show that the degradation rate is slow and the copolymer can stay at least 3 years in vivo. It is suitable for long acting drugs.Based on PCL/PLA block copolymer, microspheres carried β-hCG, hepatitis vaccine,insulin were prepared by double emulsion solvent evaporation method. The stability and bioavailability of the drugs were improved.2. For improve the properties of the biodegradable copolymers of PCL/PLA series, D,L-3-methylglycolide (MG) was synthesized. By an improved method, the.yield of the MG was improved from <15% to 42%. MG copolymerized well with.PLA and PGA, and three-arm and four-arm star-shape PCL-b-PMG copolymers. The.degradation and drug releasing properties may adjust by balance the degradation rate as well as diffusion and erosion degradation process..3. For improving the hydrophilicity of the biodegradable polymers,polyethylene.glycols, glucosamine were introduced into the polyester. Hydrophilic monomers uchas 3-benzyloxymethyl-1,4-dioxane-2,5-dione (BMG) was also synthesized for this.purpose. Copolymers of PLA or PCL with BMG were prepared. The microsphere.encapsulations of polypeptides/proteins by these copolymers were prepared by double emulsion solvent evaporation method. Hydrophilicity of the polymers was found to have great influence on both the size of microspheres and the encapsulation efficiency of polypeptides/proteins. Drug loading of microspheres prepared with deprotected.copolymers was increased because of the stability of primary emulsion was improved.The stability and bioavailability of these drugs were also improved.All these results will expand the possibility of application of the polymeric polypeptide/protein drug delivery systems in medical and family planning areas.

设计全盛一类新型的能调节其亲脂性和亲水性的生物降解聚酯糖类嵌段共聚型医用高分子复合材料，并以此为载体材料研制多肽与蛋白类药物的近释体系，探讨药物释放规律的机理，提高药物的有效性和生物利用度，解决用于人口控制或疾病防治的多肽与蛋白类药物近释体系的关键性基础科学问题，从而把多肽与蛋白类药物近释体系的研究和开发推向新的阶段。.