Studies Of Thermosensitive Insulin Anal Liquid Suppository

Objective:Thermosensitive insulin anal liquid suppository, its content includes content determination method、preparation、in vitro release、 stability and irritating、pharmacokinetics and pharmacodynamics. Method:To establish HPLC-UV determination of insulin levels in thermosensitive insulin anal liquid suppository method. Chromatographic column to Welch ultimate C18, mobile phase0.2mol· L-1sulfate buffer-acetonitrile (74:26, V: V);Flow rate1.0mL·min-1;Detection wavelength of214nm; Column temperature40℃; Sample quantity including20μL. With the orthogonal experiment to form gel time as examining index to determine the thermosensitive insulin anal liquid suppository of preparation technology. Reviewed by membrane dialysis test of corrosion situation, with biofilm (cattle sheep intestines mucosa) the absorption of the simulated intestinal mucosa on drug release test, with dialysis bag for studying’ drug molecular weight (size) to enter the body. Preparation of, carries on the experiment of high temperature, high humidity test, glare test, inspect thermosensitive insulin anal liquid suppository of stability. Adopt the method of determination of serum insulin the pharmacokinetic process of diabetic rabbit, calculating the main pharmacokinetic parameters. Through the determination of blood sugar levels to investigate thermosensitive insulin anal liquid suppository on normal rabbit rabbit’s fall blood sugar and diabetes. Results:The methodology, the content determination method is simple and accurate, and insulin thermosensitive insulin anal liquid suppository in the range of1.0-40.0IU inside have good (r=0.9991), the average recovery of99.35%, RSDO.79%. Through orthogonal experiment, the optimum preparation process for P407and P188ratio, therefore the chitosan0.4%, pH5±0.2. No film release:Q=0.4954t-2.6118(r=0.9977);Cattle bowel mucosa release (1-Q)1/3=0.0016t+2.9274(r=0.9755);gut mucosal release:lnQ=0,87831nt-4.931(r=0.9705); Dialysis bag release:lnQ=0.23lnt-2.1936(r=0.9839), in vitro release studies have shown that drug is through diffusion and dissolution into the body. The main pharmacokinetic parameters:Tmax low、medium and high dose group:(90.0±21.2),(90.0±18.9),(78.0±24.0) min; medium’and high dose group:(109.7±36.6)、(115.2±28.1)(151.3±40.3)μIU· mL-1;Relative bioavailability is low, medium and high dose groups:32.86%,20.20%,15.31%. Doses of thermosensitive insulin anal liquid suppository can reduce the blood sugar of diabetic rabbit, elevated serum insulin concentrations. Conclusion:Thermosensitive insulin anal liquid suppository medicine after every dose group of diabetic rabbit blood sugar and serum insulin levels rise compared with saline group had significant differences(P<0.05). Thermosensitive insulin anal liquid suppository can be absorbed by the rectal mucosa.