Study On The Preparation Of CTSHD And COSTD And Their Anti-obesity Effect

Obesity is the excess calories stored in body in the form of fat when the body intakes more calories than it consumes and the amount of fat exceeds the normal physiological needs.The harm caused by obesity to human beings can not be ignored.At present,there are fewer types of anti-obesity drugs,and most of drugs have adverse effects.Therefore,it is urgent to find safe,effective and non-toxic anti-obesity drugs.Chitosan(CTSH)is a kind of natural macromolecular polysaccharide which is safe,non-toxic and has a variety of biological activities,and it has been widely used in the field of medical biology.Chitosan oligosaccharides(COS)is the product of CTSH degradation,which is soluble in water and has a better biological activity.Dropping pills have the characteristics of improving the dissolution of insoluble drugs,improving the bioavailability and increasing the stability of drugs.Therefore,CTSH and COST(Mw ? 1000Da)were prepared into chitosan dropping pills(CTSHD)and chitosan oligosaccharide dropping pills(COSTD),which can improve the solubility of CTSH and the instability of COST.In this study,the preparation methods and quality standards of CTSHD and COSTD were explored.The activity of weight-loss activities of both of them were studied by animal experiments,and the mechanisms of anti-obesity effect were preliminarily discussed.The experimental results showed that the prepared CTSHD has a round appearance with uniform color and luster,average weight difference of 3.99%,average dissolution time of 11.61 minutes and dissolution rate of more than 90% within 45 minutes,both meeting the requirements of the Chinese Pharmacopoeia.The content of the CTSHD is 22.16%,and the method was stable.The dissolution rate of CTSHD was significantly higher than that of CTSH capsules(CTSHC)and CTSH tablets(CTFTs)at the same time,which proved that the dissolution of CTSHD could improve the dissolution rate.The prepared COSTD showed a round appearance with uniform color and luster,the average difference of weight and weight was 3.35% and the average dissolution time was 7.80 minutes,both of which met the requirements of Pharmacopoeia.The content was 26.82%,and the assay method was stable.Animal experiments showed that CTSHD and COSTD significantly reduced high-fat diet(HFD)induced weight gain in SD rats and reduced total fat content in rats without affecting the appetite.The effects of high and middle doses of CTSHD and COSTD are similar to Orlistat,which have a good anti-obesity effect.In the study of lipid metabolism,CTSHD and COSTD significantly decreased serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),free fatty acid(FFA),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bile acid(TBA)and glucose(Glu),and increased the contents of high density lipoprotein cholesterol(HDL-C).At the same time,the contents of TC,TG and FFA in liver and TC,TG and TBA in feces were also reduced by CTSHD and COSTD.It is demonstrated that CTSHD and COSTD can improve the lipid metabolism in serum,liver and feces,and ameliorated the liver injury or pathological changes.Furthermore,the results of tissue slices showed that CTSHD and COSTD can also inhibit the growth and expansion of white adipose tissues,improving the obesity and its complications.The weight-loss activity were compared between CTSHD and CTSH,CTSHC,CTFTs.Results showed that CTSH,CTSHC and CTFTs also significantly reduced weight gain in obese rats and improved lipid metabolism levels in serum,liver,and feces,inhibiting the expansion and growth of white adipocytes.Overall,anti-obesity effect of CTSHD slightly was better than that of CTSH,CTSHC and CTFTs,which may be the reasons why dropping pills improved the dissolution of insoluble drugs,thereby enhancing their bioavailability.CTSH and COST were found to significantly downregulate SREBP-1c,FAS,ACC and HMGCR mRNA expression in liver and PPAR?,C/EBP?,ADRP,SREBP-1c and FAS mRNA expression in WAT by using RT-PCR,which reduced the fat synthesis in the liver and inhibited adipocyte differentiation,growth and aggregation,thereby improving the liver lipid metabolism and body fat content,and play a role in weight loss.