Pharmaceutical Basic Research Of Huangkui Capsules Active Site

Huangkui Capsule is made of the active ingredients extracted from Abelmoschus manihot(L.)Medic.It is widely used in the treatment of Chronic kidney disease.But the extractes were strongly hygroscopic,and patients need to take great does of Huangkui Capsule(three times a day,once five).So this study is about the development of Huangkui Capsule,includes the literature research,technology research,quality standards and the comparison of development process and the current process.1 Literature researchThe composition of Abelmoschus manihot,the clinical application of Huangkui capsule,mechanism of action of the active site and the preparation of Huangkui capsule were discussed.2 Process research2.1 The content of the total flavonoids and the 5 substances were as the indicators,the Box-Behnken response has been used to optimize the extraction process,the ideal extraction process was 2 times of extraction,20 times of 72%alcohol,50min of reflux.2.2 Optimize the process parameters of purification of total flavonoids by microporous resin.The recovery rates of total flavonoids?hyperoside?isoquercitrin?myricetin?rutin?quercetin and the purity of total flavonoids were used as indicators,orthogonal experiments were used to determine the optimal purification process.The optimized parameters were as follow:the concentration of total flavonoids was 4.23mg/mL,PH was 4.17,the sample flow rate was 1BV/h,5BV water and 3BV 5%ethanol were used to remove impurities,eluting solvent was 70%ethanol,eluting speed was 1BV/h,elution volume of ethanol was 7BV2.3 Moisture absorption rate and amount of accessories were used as indicators,orthogonal experiments were used to optimize the molding process.The results were adding 15%calcium hydrogen phosphate and 3%silica powder.3 Quality standards3.1 The current standard of TLC were optimized,with 80%water microemulsion solution:acid:ethyl acetate mixed by 9:1:1,can identify rutinum,hyperoside and quercetin.3.2 Based on the current standard,add dissolution testing,with 0.5%SDS aqueous solution,using paddle method,75r/min,sampling in the 45min,the dissolution rate of hyperoside and isoquercitrin must be more than 85%.3.3 Determination of the content of the current standards were optimized by adding the content of total flavonoids and rutinum,hyperoside,isoquercitrin,quercetin,myricetin.3.4 Add quality control standards of intermediate product,including:Character,identify and determination of content.4 Comparison of development process and the current process4.1 Biological effectiveness:The current extracts?the total flavonoids extracts?the impurity extracts were used for the treatment of adriamycin nephropathy rats.24h urinary protein,urinary NAG enzyme activity,urea nitrogen,creatinine,total protein,albumin,total cholesterol triglyceride were used as indicators,the results showed that total flavonoids extracts and current extracts had the same treatment effect,and the higher the dose,the better treatment,but the impurity extracts did not show the treatment effect.4.2 Comparison of total flavonoids content:by optimizing the extraction process,the content of total flavonoids change from 4.08%to 6.3%;for the dried extract,total flavonoids accounted from 13%to 58%.4.3 Comparison of hygroscopicity:At 92%relative humidity environment,the moisture absorption rate of the deveiopment dired extracts were 17.0422%,but the current dried extracts were 48.6483 in 168h.The hygroscopic shows significant improvement.4.4 Dissolution testing:By using silica powder instead of magnesium stearate,the dissolution rate of hyperoside and isoquercitrin were faster than before.4.5 The dosage:Oral dosage of Abelmoschus manihot was 30g a day.The Huangkui Capsule was 0 capsule,three times a day,once five,but the development capsule was 1 capsule,three times a day,once three.5 The innovation point5.1 The development had optimized the extraction process,microporous resin was used to optimize purification process,change the flow aid.So that the hygroscopicity was significantly improved,the dissolution rate was than before,and the dose was lower.5.2 The study establish the quality standards of intermediate products and finished product,optimize the TLC,add dissolution testing and determination of the content of total flavonoids,rutinum,hyperoside,isoquercitrin,quercetin,myricetin.5.3 Significantly reduced the extract hygroscopicity and capsule dosage without changing the efficacy.