| Objective:Using gum Bletilla as the main film-forming material,to research and develop clinical trials valid and experience prescription for the treatment of cervical cancer-EHS,which was used by Province Professor Wang Xiuxia,the prominent veteran TCM doctor with national second batch of outstanding students and famous TCM doctor in Hei Longjiang.To make it possible to be a kind of sustained release bilayer membrane preparations that could achieve the "drug auxiliary double effect",and to provide an effective modern Chinese medicine for the Chinese medicine treatment of cervical cancer,and accumulated data for the study of traditional Chinese medicine agent at the same time.Method:Firstly,HPLC analysis methods of berberine,Martin,coptisine and table berberine in coptis chinensis as well as catechin,epicatechin in catechu were respectively establish.And a method for determination of in vitro release rate was established by investigating the impact of receiving liquid,the measured film and rotating speed for the release model,furthermore the release curve was drawn and the release model was analyzed.Then,the slurry state,film,off film,uniform,sticky even,smooth,flexibility,adhesion and in vitro release were used as investigation indexs,single factor comparison test method,design-response surface method optimization method were used to optimize the prescription and preparation process of the EHS bilayer membrane preparation.Finally,according to the provisions of the Chinese PHarmacopoeia(2015 Edition(second part)of appendix IM film preparation,appearance,weight difference,pH value,release degree of EHS bilayer membrane agent were investigated,using TLC method for the identification of membrane agent of Rhizoma Coptidis alkaloids and catechin,HPLC method of Rhizoma Coptidis berberine hydrochloride,hydrochloric acid palmatine,coptisine,table of berberine and catechol catechin and epicatechin content determination..Results:This paper established high performance liquid chromatography(HPLC)analysis methods of rhizoma coptidis alkaloids and acacia catechu as follows:rhizoma coptidis alkaloids:acetonitrile-0.05 mol/L sodium dihydrogen phosphate(45:65)(0.4 g of sodium dodecyl sulfate SDS-Na was added into each 100 mL of the mixture,and phosphate was used to adjust the pH into 4),detection wavelength at 345 nm,flow rate at 1 mL/min,and column temperature at 35℃.Acacia catechu:water-methanol gradient elution conditions were shown in Table 2-5,detection wavelength at 280 nm,flow rate at 1 mL/min and column temperature at 35℃.The final determination method of in vitro release degree was as follows:drug release conditions:0.1 mol/L hydrochloric acid was as accept medium,measurement membrane was dialysis bags,and speed was 400 r/min.The drug releasing model analysis showed that the in vitro drug release behavior was in line with a first-order kinetic equation,the drugs can be better released in vitro,and the drug release was in line with the specified sustained release preparation release principle by "Chinese Pharmacopoeia"(2015 version).Central composite design-response surface method was optimized to obtain the optimal prescription composition of the acacia catechu drug film layer:CMC-Na concentration at 1.61%,rhizoma bletillae concentration at 3.81%and glycerol at 8.49%;rhizoma coptidis and alum drug film layer:HPMC concentration at 1.15%,rhizoma bletillae concentration at 3.41%and glycerol concentration at 10.02%.The acacia catechu and rhizoma coptidis double-layered film agent showed an appearance property with upper and lower film agents,the rhizoma coptidis and alum drug film layer was yellow,the acacia catechu drug film layer was brown,and the two film agents were complete and smooth in appearance,consistent in thickness,uniform in color,free of obvious bubbles,and suitable in softness.The average weight of each film agent(10 cm2)was 0.9871 g and the pH value was 6.78-6.81.TLC method was used to conduct a qualitative identification of the rhizoma coptidis alkaloids and acacia catechu in the double layered film agent.The results showed that the spot size and the spot position of the test sample were the same as those of the control sample,and the test sample was negative and free of interference,and met the requirements.Berberine hydrochloride,palmatine hydrochloride,coptisine,epiberberine,catechin and epicatechin were used as index components,HPLC was used to conduct content measurement of the acacia catechu and rhizoma coptidis double-layered film agent,the negative sample was free of interference,and the standard curve showed a good linearity.Each tablet of the product(10 cm2)was tentatively to contain berberine hydrochloride,palmatine hydrochloride,coptisine and epiberberine being less than 9.04 mg,1.336 mg,1.00 mg and 0.864 mg,respectively and contain catechin and epicatechin being not less than 4.992 mg and 0.536 mg,respectively.Conclusion:The method of,prepared EHS as "medicine auxiliary double effect" sustained release bilayer film former in this subject was stable and feasible,and was provided with features as advanced formulations,science and technology,quality control,ease of use,as well as drug safety. |
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