| Ganershu preparation,consisting of the three classic prescriptions,Sini powder,Yinchenhao decoction from "Febrile Diseases" and Zhizhu pills from "Differentiation on Endogenous and Exogenous Diseases",has been used as hospital preparation for thirty odd years.The constitution of this prescription is rational and have good curative effect on protecting liver and lessening enzyme.It has been proved for many years that the prescription can be used for adjusting liver,strengthening spleen and clearing up wet and fever and has very notable efifect on acute or chronic hepatitis,stagnation of liver-QI with deficiency of the spleen and syndrome of accumulated dampness-heat.Due to traditional mixture go bad easily when placed for long time and is inconvenient to carry.In addition,chronic hepatitis patients need to take medication for long time,patients are not easy to accept the dosage form or the taste.By vast exploratory pretesting,we enrich and purify effective fractions and subsequently make the effective fractions into capsules,So that the clinical medication could be less medication long dosing intervals and better compliance.This study has strong application value and practical significance.Ganershu sustained-release capsules,consisting of the total Flavonoids,Saponins,total Alkaloids and total Organic Acids,belongs to the sixth new Chinese traditional drug.Enrichment and purification of effective fractions,pharmacodynamic screening and optimization of moulding technics are accomplished in the preceding work.In this study,according to the provision of the sixth new Chinese traditional drug,we carried on researches of pharmacodynamics on effective fractions of Ganershu.Simultaneously,release characteristics in vivo and in vitro of Ganershu sustained-release capsules are experimented,then the quality standards and stability of the Ganershu are studied.The research above could provide adequate guarantees for ensuring safe,effective and stable and controlled quality of the product.The main methods and results of this essay are as following:1.Study on the PharmacodynamicProtective effects of Ganershu on a variety of liver injury models are investigated and also the impact of drugs on the immune function and bile secretion are investigated.The results suggest that better protection Effect of Ganershu is showed in acute liver injury mice induced by CCU,Ganershu can significantly reduce the content of ALT,AST and MDA in serum,increase GSH-Px activity and reduce liver index and pathology score.In chronic liver injury rats by CCU,liver index,content of ALT,AST,MDA,Hyp and pathology score also can be reduced,while A,A/G,SOD and GSH-Px levels are significantly higher.In immunological liver injury rats by Swine Serum,the drug can reduce the liver index,ALT,AST,Hyp and pathology score,while increasing A and A/G.But the experiment that effect of Ganershu on phagocytic activity of peritoneal macrophages in mice is no significant impact.Based on the studies of the above,the protective effect of Ganershu may be function through anti-oxidative pathway,rather than immunomodulatory approaches.Therefore,the drug i5 more suitable for reversing liver function abnormalities in patients with hepatitis and plays symptomatic treatment of protecting liver and debasing enzyme.While the temporary promoting bile excretion of Ganershu also conducive to adjuvant treatment of cholelithiasis,cholecystitis.2.Study on the Sustained-release EvaluationAn active monomer ingredients(Naringin)and an effective fraction(total Flavones)are respectively used as evaluating indicator to measure the release degree in vitro of sustained-release capsules and normal capsules and discuss the release mechanism,so as to evaluate its release characteristics preliminary.The results show that the accumulative releasing degree of total Flavonoids and Naringin in normal capsules are more than 90%in lh,while the releasing are slow in sustained-release capsules and the accumulative releasing degree of two are more than 90%in 12h.We determine this sustained-release formulation is not synchronized release and the release mechanism is the initial framework for the diffusion and erosion synergy.The evaluating researches in vivo determine the blood concentration of Naringenin by HPLC in dogs at different time points.By comprising the pharmacokinamic parameters between sustained-release capsules and normal capsules,including the half-time,the peak concentration,the residence time in vivo and the apparent volume of distribution and so on,the results suggest that the half-time is extended by 2.4h,the residence time in vivo is lengthened,Cmax is decreased and Tmax is extended,which preliminarily evaluate the sustained-release characteristics of Ganershu sustained-release capsules.3.Study on Quality StandardsThe TLC method is used to identify Sarmcntosum,Citrus Aurantium,Radix Paconiae Alba,Rhizoma Corydalis,and Wormwood in Ganershu sustained-releasing capsules,and it is proved that the reproducibility is good through several tests.The HPLC method is used to determine Quercetin,Kaempferol,Isohamnetin,Naringin,Hesperidin,Glycyrrhizic acid and Gallic acid,all methods are realistic and manageable with good reproducibility.At the same time,moisture,size distribution,content uniformity and releasing rate are meet the requirement measured according to the relevant provisions of the current pharmacopoeia.In the end,we have basically made the draft quality standards of the Ganershu sustained-release capsules.4.The Investigation of Preliminary StabilityThe character,TLC identification,moisture,size distribution,releasing degree in vitro,content of active components,and microbial limit of the sample are investigated under the condition of accelerating test and room temperature respectively in six months,according to "the instruction principle on stability of traditional Chinese medicine and natural medicine".It is proved that the quality of capsules are basically stable and the term of validity is tentatively designed for 24 months according to the results of stability investigation. |
PDF Full Text Request