Study On The Preparation And Quality Standard Of Dispersible Tablets Of Radix Adenophorae Potanini Korsh Polysaccharides

Radix Adenophorae Potanini Korsh Polysaccharides (RAPS) was extracted from Adenophora tetraphylla(thunb.)Fisch or A. stricta Miq. It has development prospects because of its wide range pharmacological effects. But there is no relevant commercial preparations, so its application was limited. Based on the basis of preliminary studies, we developed the dispersible tablets of Radix Adenophorae Potanini Korsh Polysaccharides(RPDTS) using modern pharmaceutical excipients, immediate-release technology, prescription screening and process optimization. RAPS can be rapidly collapsed and released from RPDTS, by the immediate-release system to show a full pay to efficiency.And these features would show a improving to the bioavailiability and will become the basis of innovation in Traditional medicine finally.First,The polysaccharide was isolated and extracted from Radix Adenophorae by water extraction and alcohol precipitation, the methods for the content determination of RAPS were established and compared. The standard curve was established using glucose as standard. The content of RAPS was determined by anthrone sulphuric acid colorimetry and phenol-vitriolic colorimetry using UV spectrophotometer. the content determination result using anthrone sulphuric acid colorimetry method was16.37%, the recovery was101.1%,RSD was2.1%; and the content determination result using phenol-vitriolic colorimetry method was15.26%, the recovery was99.9%, RSD was1.8%. So the two methods were reliable and accurate, they all can be considered as the assay methods for the content determination of RAPS.The preparation technology of RPDTS was chosen by studying the micromeritics of drug and adjuvants. The prescription was optimized by single factor screening and orthogonal test method. The results showed that the powder pellets method was adopted in preparing the dispersible tablets, the prepration process was simple and reproducible. An optimized prescription as follow:30%of Radix Adenophorae Potanini Korsh polysaccharides power,43%of calcium hydrogen phosphate,15%of PVPP,10%of PEG4000,1%of colloidal silicon dioxide and1%of magnesium stearate. The experiments showed that disintegration time was less than60seconds, dispersible homogeneity was good, and dissolution rate was more than85%in15minutes.The quality standards of the RPDTS was studied in terms of the relevant provisions of dispersible tablets on2010versions Chinese Pharmacopoeia, including appearance, character, identification, weight variation, dispersion uniformity and dissolution, etc. RPDTS was shallow white tablets, the content of RAPS should not be less than111mg in each tablet, the dissolution in15minutes should not be less than85%. The preparation process was reasonable, practicable and affordable. The established quality standards could complete control the dispersible tablets quality and it also offered quality assurance for clinical medication. The results of initial stability test showed that RAPS was sensitive to humidity, After RPDTS was packaged by aluminium-plastic, the accelerate test and long-term stability test showed that tablets did not change significantly compared with0month.In order to evaluate the acute toxicity of RPDTS objectively, We not only studied the acute toxicity of RPDTS, but also studied the acute toxicity of RAPS by gavage administration and intraperitoneal injection administration. The mice were chosen, firstly acute toxicity was estimated by Once-daily dose method and three times daily dose method through pre-test; the maximum dose test was measured by intragastric administration of RPDTS and RAPS, the maximum tolerable dose test was measured by intraperitoneal injection administration of RAPS, the toxic symptoms to mice were observed and recorded. All mice were survival after14days, the maximum dose test showed that the total dose of intragastric administration of RPDTS and RAPS were208g/kg and555g/kg (according to Adenophorae tetraphylla(thunb.)sch), respectively,equivalent to men’s clinical dose by320times and120times;the maximum tolerable dose test showed that the total dose of intragastric administration of RAPS was65.2g/kg, equivalent to men’s clinical dose by38times. The acute toxicity of RPDTS and RAPS were lower and safer.To study on the protective effects of RPDTS on acute liver injury. The mice were chosen, The acute liver injury model was induced by Carbon tetrachloride and D-galactosamine, The effects of RPDTS on levels of ALT,AST in serum and T-SOD,MDA,GSH-Px in liver were studied. The results showed that RPDTS could obviously decrease the levels of ALT and AST in serum and MDA in liver, and obviously increase the activity of T-SOD, GSH-Px in liver; The pathological changes revealed that liver injury was relieved.This study showed that RPDTS has protective effects on acute liver injury in mice induced by Carbon tetrachloride and D-galactosamine. Its hepatoprotective mechanism may be related with that RPDTS can increase the T-SOD and GSH-Px activity in liver cells, then against free radical-induced membrane lipid peroxidation, thereby reducing the degree of cell membrane damage, promoting the regeneration and repair of liver cell.