Study On The Preparation Of Norathyriol Solid Dispersion Tablets And Therapeutic Effects On Hyperuricemia

A series of studies have shown mangiferin has a wide range of biological activiti es and pharmacological effects,such as antioxidation, antitumor, antiviral, anti hyperur icemia and diabetes. Mangiferin’s molecular structure belongs to polyphenols hydroxy diphenyl and pyranoid ketone carbon glycosides, and its chemical properties is quite special,which is poorly soluble in water, but insoluble in organic solvents, and difficul t to be absorbed. So with a low bioavailability, mangiferin is defined as the fourth cla ss of biopharmaceutics,what seriously limits its clinical application.Norathyriol, as the active metabolites of mangiferin, without the glycosyl, not on ly retaines the active group of double phenyl pyrazole ketones, but also reduces the m olecular weight,which makes it easy to get into cells and much more water-soluble.M eanwhile,it will combine with hydrophobic sites of xanthine oxidase availably.In addi tion, norathyriol has more advantage than mangiferin on curative effect of the individ ual differences caused by gastrointestinal bacterial species and amounts in the human.Thus,the significant improvement of the absolute bioavailability makes norathyriol h ave a broad prospects in clinical application.Rats and mice were given with Norathyriol separately.HPLC was used to detect the amount of Norathyriol in tissue distribution(plasma、live、heart、spleen、lung and kidney) after oral administration at seven time point. The plasma concentration was deteminated by HPLC and the pharmacokinetic parameters were analyzed. According to carry out an acute toxicity test, the maximal tolerance dose was76.86mmol/kg,which proved the high safty of this medicine and much safer than positive drug allopurinol.Reasonable experiment groups with hyperuricemia mice model induced by oxyg en oxazine acid potassium were set up, and the uric acid(SUA) content,xanthine oxidase(XOD) and adenosine deaminase(ADA) were detected by the relevan t kits.Western blot method was used to study the expression change of XOD and ADA in kidney.Thus,the effect of norathyriol on the uric acid reduction were evaluated in pharmacodynamics and molecular level.This study used norathyriol to prepare solid dispersions instead of mangiferin. Si ngle factor experiment and orthogonal experiment were used to explore the optimum prescription and preparation technology by the standard of releasing degree. To detect the concentration and the releasing rate of the solid dispersions by ultraviolet spectro photometric method,and to identify the phase of the solid dispersions by infrared spe ctroscopy, the corresponding method were established.The established method is simp le, and has a good linear range and higher recovery rate.The results showed that the melting method of preparing norathyriol solid dispersions: using PEG6000 as a carrier material, medicine and auxiliary ratio 1:60, melting temperature: 80 ℃,stired 15 min,vacuum drying 48 h,by vacuum drying solid dispersions had a higher release degree i n vitro.To further investigate the prescription of preparing norathyriol solid dispersions in to dispersible tablets,dispersible tablet disintegration time and disperse uniformity wer e acted as the evaluation standard. The prescription was examined on the disintegratio n time and dispersion uniformity,and the optimal prescription and preparation of norat hyriol solid dispersion tablet was prepared after the orthogonal design method.The op timal prescription is: L-HPC and CMC--Na as disintegrating agent, microcrystalline c ellulose(MCC) as the filler, a certain amount of micro powder silica gel as a lubricant to direct tableting prepared tablets.As a result, according to the optimized prescriptio n preparation, norathyriol solid dispersible tablets completely disintegrated and disper sed within 3 min.To evaluate the quality of norathyriol solid dispersible tablets, the HPLC method was established to determine the content of norathyriol.This method has a strong speci ficity, high sensitivity, good recovery and repeatability, so the results are accurate andreliable.Continuous preparation of norathyriol solid dispersible tablets within three ti mes had small tablet weight variation, and the friability, dissolution, disintegration an d uniform dispersity were all in accordance with the requirements of the Chinese Phar macopoeia.