Study On Long-acting Insulin Delivery System In The Treatment Of Diabetes Mellitus

Insulin is a kind of proteins secreted by islet beta cells to regulate carbohydrate metabolism to control blood glucose balance,which is widely used to treat diabetes.Currently subcutaneous administration is still the main mode of administration.Due to the short half-life and poor bioavailability of insulin,ordinary insulin preparations need to be injected 3-4 times within day,which gives patients a great pain,therefore,it is important to develop new long-term delivery system.In this study,two kinds of implanted dosage forms were used to study the sustained release of insulin.(1)Preparation of poloxamer hydrogel,with the gelation temperature and viscosity as an index,by examining the different proportions of P407 and P188 and the effect of adjuvants on the gelation temperature and viscosity,a better prescription was identified and then The insulin nanoparticles and microspheres were loaded into the gel for in vitro and in vivo studies.(2)Preparation of insulin solid implant,by adjusting the PLGA and hydrophilic substances(sodium hyaluronate,sodium carboxymethyl cellulose)ratio,screening the appropriate prescription,hypoglycemic pharmacodynamic study.In the first part of this paper,the method of insulin determination was established by high performance liquid chromatography(HPLC).The concentration of insulin was in the range of 0.5-10 IU/mL,and the concentration was linear with the peak area.Method stability,precision,recovery results are in line with the provisions of the determination of insulin for in vitro determination.At last,the rat diabetes model was established and the determination of blood glucose methods and precautions were also il uminated.In the second part of this paper,prescription screening and prescription optimization of poloxamer injection were carried out.Three gel prescriptions were selected by the gel temperature and time.We selected P188: P407: HPMC = 9: 20: 3,P188: P407: SA = 9: 20: 2 and P188: P407 = 9: 20 three prescriptions from the viscosity,FIRT,SEM and other aspects of characterization.The release of insulin crystals or insulin microspheres in vitro and in vivo were studied.From the experimental results can be seen that hypoglycemic effect of temperature sensitive hydrogel loaded insulin microspheres prescription can last three days.The third part of this paper,solid implantation prescriptions were screened.Solid implant agent for the degradation were PLGA and hydrophilic substances.The appropriate prescription were selected by hardness test,in vitro dissolution and other means.The experimental results shows that solid implant can continue to steady blood glucose five days,which greatly reduces the number of times the administration of insulin,improving the patient’s adaptability.