Therapeutic Effect Of A Small Molecule Drug Targeting Inflammatory Bowel Disease

Inflammatory bowel disease(IBD)is a chronic,nonspecific intestinal immune disease characterized by diarrhea,abdominal pain,bloody stools,and even severe death.Its etiology and pathogenesis are not completely clear,and it is generally believed that it may be related to factors such as heredity,environment,immunity,and intestinal flora.The proportion of patients with inflammatory bowel disease in China has increased year by year.Although many treatments and therapeutic drugs have appeared in the market to relieve inflammatory bowel disease,they cannot be completely cured.Therefore,it is of great significance to explore a therapeutic drug that is very effective and has low side effects of inflammatory bowel disease.The previous computer-aided drug design of our research group found a chemical active ingredient LFS-01 derived from traditional Chinese medicine,and its derivative LFS-829 was obtained through modification.In this study,the active ingredient of Chinese medicine LFS-01 was determined by using a mouse model.LFS-829 studied the therapeutic effects of IBD.Finally,the cyclodextrin embedding method was used to make the drug more effective and bioavailable.The main conclusions of the study are:(1)The IBD model induced by DSS in C57BL/6 mice was used to evaluate the efficacy of LPS-01,a natural product derived from Chinese herbal medicine,in reversing the pathological symptoms of IBD through the evaluation of the efficacy of the control,model,and administration groups.And explained that LFS-01 is effective in the treatment of IBD by modulating the disorder of the intestinal microflora caused by inflammation.(2)LFS-829,a more active derivative,was designed against a series of modifications of LFS-01.The series of efficacy evaluations of IBD models induced by DSS validated that the LFS series derivatives LFS-829 can also effectively reverse IBD pathology.symptom.Compared with 5-aminosalicylic acid,which is the same dose of traditional IBD treatment agent,LFS-829 showed a better reversal effect on pathological symptoms of IBD than 5-ASA.LFS-829 can be used as a candidate for clinical treatment of IBD for further study.(3)By examining the indicators of the pharmacokinetics of ADMET in LFS-829 in vitro,it was found that very large doses of LFS-829 are basically non-toxic to animals,ie,they have better safety.In order to maximize its effect,we have designed ?-cyclodextrin-embedded LFS-829 small molecules to enable small molecules to have better stability in vivo and to increase intestinal targeting,which can be more efficient.Play its role in the treatment of IBD.This study has found a natural product chemical active ingredient LFS-01 for the treatment of IBD and found effective treatment of IBD.In order to improve the therapeutic effect,the method of assisted computer drug design has produced a more active derivative LFS-829,and animal efficacy trials to verify the treatment of IBD.According to the special nature of the derivative small molecule,the method of cyclodextrin encapsulation was found to make the drug more stable in the treatment of IBD,improve the efficiency of IBD treatment,and create gospel for more IBD patients.