Curcumin-quercetin Compound Self-microemulsion Preparation And Pharmacodynamic Evaluation

Objective:Curcumin is a natural active ingredient extracting from the root of Curcuma longa L.plant,which is often used as anti-inflammatory,antiviral,anti oxygen free radicals,anti-tumor and other pharmacological effects.Due to its low water solubility,poor stability,exist in the gut metabolism leads to disadvantages such as limitation of its clinical application.In order to improve the shortcomings of curcumin,the early application of mature,clinical study of glucuronic acid effective transfer enzyme inhibitor compatibility of piperine and curcumin,combined with the pseudo three component phase diagram optimization design of curcumin and piperine compound prescription self microemulsion preparation by using the simplex grid method,effectively improves the water solubility and stability of curcumin,To avoid the effect of curcumin on degradation of intestinal mucosal surface,for the research and development of new drugs is safe,effective in treatment of ulcerative colitis and provide new ideas and methods.But the metabolic enzyme inhibitor of other natural existence,such as quercetin,research reports also can significantly improve the stability of Curcumin,oral absorption and bioavailability.So this experiment combined application of quercetin and curcumin were discussed,and the pharmacodynamics experiment compared the curcumin SMEDDS and combined with piperine,quercetin respectively,that explain the meaning of combination of curcumin and quercetin.Methods:(1)Preparation studies of CUR-QUE-SMEDDS:Establish HPLC method for determination of curcumin and quercetin;Capryol 90,Cremophor RH40 and Transcutol HP were chosen as oil phase,surfactant and co-surfactant respectively,the ratio is 1:6:3.With ratio of 10:1 between Curcumin and quercetin,designed a series of dosage,preparation of CUR-QUE-SMEDDS,the particle size,entrapment efficiency(EE)and drug loading(DL)of Curcumin(CUR)and quercetin(QUE)as the index to optimize the formulation;(2)Evaluation of the quality of CUR-QUE-SMEDDS,the microemulsion appearance,morphology and particle size,Zeta potential,entrapment efficiency and drug loading as quality evaluation indicators.(3)Pharmacodynamic experiment of CUR-QUE-SMEDDS,the establishment of acute ulcerative colitis in mice induced by DSS,the simulation principle of colon targeted preparation by retention enema administration,5-aminosalicylic acid(5-ASA)as positive control drug in the colon appearance and length,disease activity index(DAI),histopathological score,colon tissue myeloperoxidase(MPO)activity,malondialdehyde(MDA)content,interleukin-6(IL-6)and tumor necrosis factor-?(TNF-?)of the content as the evaluation index,evaluate the effects of CUR-QUE-SMEDDS on ulcerative colitis,and difference among CUR-PIP-SMEDDS,CUR-SMEDDS and SMEDDS,probe into the significance of Combination Rationality.Results:The best dosage of CUR-QUE-SMEDDS is 40mg:4mg.The Cur-PIP-SMEDDS prepared was a translucent and achromatous solution with good stability.After being diluted with water,Cur-PIP-SMEDDS was consisted of small spherical drops.The average particle size was 15 nm,with nano emulsion particle size below 100nm,The results showed curcumin self microemulsion was prepared successfully.The EE and DL of the final prescription,CUR was(92.19±2.19)%,(31.74±0.3l)mg·g-1,QUR was(93.23 ±1.80)%,(2.16±0.06)mg·g-1.Pharmacodynamic test,through retention enema administration,CUR-QUE-SMEDDS can improve the model of ulcerative colitis mice can significantly improve the symptoms of pus and blood,including mental state,diet,fur glossiness,weight,clinical symptoms and defecation activities including mice,effective DAI value reduce,alleviate colon shortening,bloody stool,edema,ulcer and other symptoms of inflammation,can repair the intestinal mucosal barrier,significantly reduced the score and activity of MPO murine colon mucosa pathology,while reducing the colon tissue of mice with MDA,the content of TNF-a,and positive drug efficacy is similar to the 5-ASA;curcumin self microemulsifying drug effect is relatively weak,curcumin and pipetine compound self microemulsion enema in the treatment effect on ulcerative colitis after administration is relatively weak.Conclusions:curcumin(CUR)and piperine(PIP)were co-encapsulated into the nanoformulation called self-microemulsifying drug delivery system(SMEDDS),quercetin can significantly improve curcumin in water solubility and stability,compatibility between the two compound shows a good therapeutic effect on ulcerative colitis.Based on the experimental design,and ultimately get the best ratio of curcumin and quercetin.With each group efficacy comparison,preliminary study on the compatibility of the curcumin and quercetin.Provide experimental basis for research and reference to the development of a clear mechanism of action of curcumin,clear material basis,clinical efficacy and safety of compound oral colon quality and safety controlled,and provide new ideas and methods for the development of new drugs is effective in treating ulcerative colitis.