The Study On Exenatide Freeze-dried Powder For Injection

Diabetes is a common non-infectious disease which is caused by reduced insulin production and insulin resistance in peripheral tissues. Patients with diabetes are at higher risks for syndrome and death. Approximately 90% of all patients with diabetes are the type 2 diabetes patients. The commonly used therapeutic methods for patients with type 2 diabetes are oral antidiabetic agents and injectable insulins.The customarily used antidiabetic agents include biguanide class, sulphur urea class, alpha– glucosidase inhibitor, 2, 4-thiazolidinedione and insulin and so on. Among them, biguanide class and sulphur urea class are the most widely used for type 2 diabetes. Researches indicated that the above mentioned antidiabetic agents may have adverse effects, decrease or even loss of effects of the drug.Exenatide is a thoroughly new antidiabetic drug. The drug is the only one which can both improve glycemic and body weight control, and is considered to be a breakthrough in diabetes mellitus therapy. Exenatide (Byetta, Amylin Pharmaceuticals &Elillily Pharmaceuticals)is chemically synthesized Extendin-4, and is indicated as a therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking metformin , a sulfonylurea ,or both but who have not achieved adequate glycemic contol.Extenatide is mechanically similar to GLP-1.After administration of the drug through injection, it enhances insulin secretion, raises insulin sensitivity and improves the islet beta-cell function, which all accounts for it glycemic control properties. Because of its outstanding glycemic control property, it received praise from both patients and doctors after being approved by the FDA. In type 2 diabetes mellitus patients, when oral antidiabetic agents have no effect, or there is loss in beta-cell function and decrease in insulin secretion, injectable administration of extenatide offers an excellent option in glycemic control. What's more, it will not induce low glycemic level.As a antidiabetic drug, exenatide has an unmatched advantages.In hyperglycemia, it induces beta-cells to secrete insulin, and during hypoglycemia, exenatide dose not appear to suppress the normal counteregulatory increase in glucagon secretion, so it will not result in further degradation of glucogens.Exenatide could increase the secretion of insulin, inhibits the secretion of glucagen, reestablish a more reasonable physiological ratio between insulin and glucagon. Exenatide could protect islet beta-cells .All these properties are quite unique to exenatide. Exenatide could slow gastric emptying, reduce food in-take, suppress appetite and is beneficial to glycemic control after meals. Withal, exenatide could enhance the sensitivity of insulins.Up to now, Byetta has not entered the China drug market, the multi-centre clinical trial had been finished in September 2007, and now Byetta is in the process of importing pharmaceutical registration procedure. So, it is very significative for preparing the exenatide injectable produces in China.In this study we prepared exenatide freeze-dried produce for injection, and accomplished some pre-clinical trials. Our research provided the foundation for its clinical application.The experiments designed in our study included the preparation methods of the injectable exenatide freeze-dried produce for injection, the analysis methods about the exenatide and related substances in this pharmaceutical produce, the chemical and physical characters of this pharmaceutical produce, stability research of this pharmaceutical produce, the quality standardization of this pharmaceutical produce, the research of is biological activity in vivo and in vitro, the elementary evaluation of its security and therapeutic effect.A reliable HPLC analysis method of the exenatide content and related substances in this pharmaceutical produce was established. The sensitivity and recovery rate of this method coule fulfiled the requirements of analytical demand. Above-mentioned method is applicable to the quality control of this pharmaceutical produce. In this study we determined the prescription, preparation method and freeze-dried procedure of this pharmaceutical produce, and 3 batches of the drug were prepared. The chemical and physical characteristic and stability of the drug were examinated. On this basis, quality standard of the drug was established, and the 3 batches above mentioned were proved could suffice to the quality standard prescribing. Comparison of the drug prepared in our study with Byetta of the Elililly Pharmaceuticals indicated that our pharmaceutical produce had the same effect on glycemic controlling. Haemolytic test, allergic test and subcutaneous injection stimulating test results indicated that this drug could satisfed the safety requirements of injectable drug. All these pre-clinical studies provided basic data for the trial registration of the drug.