Preparation And Evaluation Of Warm Water Gel Patc

Objective:Based on the theory of traditional Chinese medicine external treatment,this study was aimed at improving the dosage form of the Xiao Shui Fang(XSF),aiming at the problems of inconvenient administration,easily contaminating clothing and poor compliance of the patients as extractum.The design of warmer pad combined with Wen Re Xiao Shui(WRXS)Gel Paste acting to the Shenque point was a new kind of administration for malignant ascites.It had given full play to the advantages of the TCM external treatment combining with the hot iron therapy of TCM in the treatment of malignant ascites.The preparation prescription of WRXS gel paste was screened and optimized in this study.Effects of warmer pad on gel paste in temperature,viscosity and release rate of geniposidic acid(GPA)were also evaluated.And the preliminary study on the pharmacodynamics,skin irritation and skin permeation components was carried out to obtain WRXS Gel Paste with significant efficacy,good stability and convenient use,which set up a foundation for further development.Method:1.Study on the prescription screening and optimizing of WRXS Gel Paste:The best prescription was optimized by Plackett-Burman design and Box-Behnken central composite design,taking initial adhesion,viscosity and peel strength by 180 degrees as evaluating indicators.2.The Effect of warmer pad on WRXS Gel Paste:viscosity index,the release rate of CAP and the temperature were as evaluating indicators.3.Study on the pharmacodynamics of WRXS Gel Paste:an ascites rat model induced by Walker-256 cell was established;the body weight,ascites volume,spleen index,thymus index was taken as indexes to evaluate the efficacy of WRXS Gel Paste.4.Skin irritation study of WRXS Gel Paste:the skin irritation test of guinea pigs was used to investigate whether the WRXS Gel Paste had skin irritation.5.Study on skin permeation component of WRXS Gel Paste:in vitro receiving solution was collected by the modified Franz diffusion cells and analyzed by UPLC-Q-TOF-MS method.Results:1.Study on the prescription screening and optimizing of WRXS Gel Paste.Optimization of the best prescription:NP 700 8g,PVPK 90 5.38g,glycerol 32.5g,tartaric acid 0.5g,Aluminium glycinate 0.5g,Herbal extract 10g,borneol 1g,Azone 2g,propylene glycol 1g,water 39.2g;borneol was dissolved in azone and propylene glycol,then the mixture was dispersed in glycerin and added to the substrate.2.The Effect of warmer pad on WRXS gel paste.1)The temperature of gel paste was changed by the exothermic behavior of Warmer pad,but there was no obvious influence of the gel paste stickiness index,which improved the comfort to increase the compliance of the patients.2)The Q8%of GAP in XS Gel paste was 52.48%,while the Q8%of GAP in WRXS Gel Paste was 62.74%.3.Study on the pharmacodynamics of WRXS gel paste.(1)Ascites:compared with the model group,the amount of ascites in rats of "XSF" extract group,WRXS Gel Paste group(with warmer pad)and XS Gel Paste group(without warmer pad)all decreased,and all had statistical differences(P<0.01,P<0.001,P<0.001),moreover,the WRXS Gel Paste group showed the best elimination.(2)Spleen index:compared with the model group,the spleen index of "XSF" extract group,WRXS Gel Paste group(with warmer pad)and XS Gel Paste group(without warmer pad)showed a decreasing trend and had statistical difference(P<0.001,P<0.001,P<0.001),The spleen index of WRXS Gel Paste group was the lowest in the three one and was no significant difference compared with the blank control group(P=0.336).(3)Thymus index:compared with the model group,the thymus index of "XSF" extract group,WRXS Gel Paste group(with warmer pad)and XS Gel Paste group(without warmer pad)showed an increasing trend,and had statistical differences(P<0.001,P<0.001,P<0.001).4.Skin irritation test of guinea pigs showed that the WRXS Gel Paste had no irritation to normal skin and drug safety.5.Study on skin permeation component of WRXS Gel Paste There were 7 components detected in the receiving solution of WRXS Gel Paste more than that of "XSF" extract.6 components were identified as geniposide,caffeic acid,coumaric acid,cinnamic acid,hydroxysafflower yellow A and isomatsteroside.Conclusion:The WRXS gel paste developed in this study was stable and feasible in preparation processes,while it had been shown to be with high efficient drug release,and siginificant efficacy of eliminating malignant ascites induced by Walker-256 cell.Six ingredients were analyed by UPLC-QTOF-MS.This study provided experimental basis for the further development of the external preparation of TCM with stability and siginificant efficacy of eliminate maglinant ascites.