Preparation And Evaluation Of Long-acting Insulin Implant

Insulin is a protein secreted by cells in the pancreas hormone,hypoglycemic effect to be used to treat diabetes,mainly for the treat of diabetes by regulate glucose metabolism and control blood glucose levels.Insulin may denature orally administered proteins due to insulin as a polypeptide chain,Subcutaneous insulin injections are main route of administration.long-acting sustained-release and controlled-release pharmaceutical preparations are more research areas.Implant can avoid the problem of oral degradation of insulin.In this study,chitosan and PLGA were used as auxiliary materials for subcutaneous implants to prepared the stability,high bioavailability and low toxicity of insulin implants,The prescription and preparation process of the implant were studied,and the pharmacodynamics of the implant on diabetic rats was studied.The specific topics of this research are as follows:A precise HPLC method of determining insulin in vitro was studied and built.In the range of 0.5-10.0 IU/mL,the linear curve was A=800396C-12612 and the relative coefficient was 0.9999.It meant that the method was accurate.RSD values of precision and stability experiments were less than 1.7%,so the method has high sensitivity and accuracy.The pharmacodynamics of insulin determination method is established using STZ-induced diabetic rats and the method of glucose-oxidase to determine blood sugar.It provide the basis for the subsequent prescription,process conditions and the efficacy determination method.The preparation and evaluation of temperature-sensitive gel implants was completed using gel temperature and the degree of difficulty of injection as evaluation indexes,temperature-sensitive gels were prepared and the factor of auxiliary materials affecting gel time,thermal stability of the reversibility of the gel,and its structure were investigated.Using high-pressure homogenization mechanism for preparation of different size particles,they were loaded in the temperature-sensitive gels.Subsequently,detetermination blood sugar of rats by the muscle stimulation test after subcutaneous injection for drugs.Finally,CS/?-GP+HP-?-CD temperature-sensitive gel loaded insulin particles were determined as the optimized prescription.The microspheres were prepared by spray-drying and the morphology size,crystal state and redistribution of the prepared microspheres were studied.The appearance of the obtained microspheres was irregular and the drug loading was 18.5% / 43%.Pharmacodynamics was studied of insulin microsphere loaded in CS/?-GP+HP-?-CD,and the CS/?-GP+HP-?-CD loaded with insulin microspheres sustained more than 72 hours in hypoglycemic effect of diabetic rats after subcutaneous injection,which sustained longer than the effect of insulin injection or insulin glargine injection.The implant tablets were prepared by using the PLGA as the insulin carrier and CMC-Na/HA as porogen with squash technique.The tablets were screened in vivo and in vitro,the degradation of the tablets was obviously after the implantation.And when the ratio of PLGA:CMC-Na is 2.5:1,hypoglycemic effect of diabetic rats subcutaneous after implant sustained more than 108 hours.