| Obesity is a chronic nutritional disease caused by the body’s unbalanced energymetabolism, which brings serious harm to human health. However, anti-obesity drugsare rather rare, and characterized with non-significant effect, rebound and more sideeffects. The research and application of anti-obesity drugs are also full of twistsand turns. These make opportunities and challenges appear in the anti-obesity drugmarket. Chitosan oligosaccharide (COS) and glucosamine (GLC) are natural productsdegraded from chitosan (CTS) by enzymatic or chemical degradation. Because ofhigh activity, novel structure, fewer side effects, COS and GLC meet withcharacteristics that chronic disease need long-term administration and play a notnegligible role in various fields.The anti-obesity effects of different CTS were study in our previous researches,such as water-soluble CTS, CTS microspheres chitosan-capsaicin microspheres andso on. But CTS has poor solubility absorption and druggability. The anti-obesityeffect of COS is a hot research and only about cell study so far. The mechanism ofanti-obesity is also not comprehensive. Molecular weight of COS was not given, andanti-obesity activity of the different molecular weights of COS was not compared.GLC is a drug for osteoarthritis which is the ultimate degradation product of CTS. IsGLC an anti-obesity drug as the ultimate degradation product?The acute toxicity of COS1(molecular weight≤1000) and COS2(numberaverage molecular weight≤3000) was assayed preliminarily. The results showed the p.o. LD50of COS1and COS2in mouse were more than21g/Kg which belong tonon-toxic substance. The maximum tolerated dose of COS1and COS2were24g/Kg.The anti-obesity research of GLC, COS1and COS2were conducted withnutritious animal model to compare the activity of COS owned different molecularweight, explore the anti-obesity activity of GLC. It indicated that GLC could reducethe weight of rats and body fat of obese rats with litter effect to appetite, showed acertain effect of anti-obesity. What’s more, GLC could significantly reduce theamount of CHO and LDL-C in serum which was better than orlistat，attenuate livercell necrosis, which had a effect of lowering blood lipids and protecting liver. COS1and COS2also significantly inhibited weight in rats, reduced the deposition of liverfat that the effect size was COS1> orlistat> COS2. The CHO and LDL-C levels inthe serum were significantly reduced that the effect size was COS1> orlistat> COS2.The deposition of hepatic lipid was reduced, and liver cell necrosis was improved,these suggested COS1and COS2have a certain lipid-lowering effect.The capsaicin-chitosan microspheres (CCMS) were prepared by techniqueconbined ionic crosslinking with spray drying in the previous research. CCMS waspowder and has phenomenon of hygroscopic, too hygroscopic to be kept. So theCCMS enteric coated tablets were prepared. The formulae of core tablet andcapsaicin-chitosan microspheres (CCMS) enteric coated tablets were optimized in thepreparation experiment. Single factor experiments were reflected that the optimalformula for the CCMS core tablet was400mg CCMS,4mg magnesium stearate,16mg sodium starch glycolate (CMS-Na) and3%(w/v) carboxymethylcellulose sodium.The optimal formula for the coating was25%talc,20%triethyl citrate (TEC) and3%coating weight with Eudragit L100. Optimized formulations showed a first-order drugrelease model in dissolution research in vitro. Release study in vitro showed thatCCMS enteric coated tablets could protect from acid corrosive, release drug sustainedin pH6.8phosphate buffer and reduced the fluctuations of plasma concentration. |
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