Breviscapine Poultice Developed

Erigeron breviseapu is the dry whole grass of Erigeron breviscapus (Vant.) Hand-Mazz, a member of the asteraceae family. It is mainly distributed in Yunnan, Guangxi and other places. Breviseapine is the flavonoid active-composition extracted from erigeron breviscapus, which has the pharmacological effects of scavenging free radicals, anti-oxidation, restraining the aggregation of platelet, the thrombogenesis, improving myocardial ischemia, anti-hypertension, anti-diabetes, etc. Clinically, it’s common that the preparation of breviseapine is used as treatments of cardiovascular disease, hypertension, and rheumatoid arthritis. Always, the preparation is taken orally or injected. But there are a lot of problems such as low bioavailability, security issues resulted from the above two methods. This thesis focuses on a new technique named transdermal drug delivery. We made the breviseapine into cataplasm, and then studied its absorptive performances in vitro and in vivo, We hope to provide a new safe and effective route of administration for breviscapine clinical application.The main study in this paper can be divided into the following six parts:1. Research on the matrix formula of breviseapine cataplasmWe chose four factors as gelatin, polyvinylpyrrolidone-K30, sodium polyacrylate, glycerin, and then conducted experiments with four factors three levels by using the orthogonal experiment method. The optimum substrate formula of breviseapine cataplasm was obtained that the ratio among gelatin, polyvinylpyrrolidone-K30, sodium polyacrylate, glycerin was2:1:2.5:12according to the first part of2010version of "Chinese pharmacopoeia", with taken the infiltration as quantitative index, as well as the sense organ guidelines like skin adhesive ability, surface homogeneity, viscosity, ductility. The verification test verified that the substrate formula was stable and feasible, and the infiltration and the sense organ guidelines were all showed to be good.2. Research on the in-vitro transdermal experiments of breviseapine cataplasmWe used chemical method to improve the percutaneous absorption of breviseapine cataplasm, and studied the percutaneous permeability of drugs by using Franz diffusion cell, in order to investigate that how different dose of azone, polysorbate80, propylene glycol, or no enhancer may affect the percutaneous absorption rate. The result showed that the maximal percutaneous absorption rate was obtained when the content of azone came to be2%. Consequently, taken2%dose of azone as the percutaneous enhancer of cataplasm, we got the percutaneous absorption rate of46.44μg.cm-2.h-1.3. Research on the forming technology of breviseapine cataplasmAfter investigating factors such as adding order of each addition, mixing rate, mixing time, mixing temperature which may affect key process and process parameters of the substrate quality, we found the proper forming technology of breviseapine cataplasm was that adding adhesive, drug and enhancer in sequence to glycerol, making them dispersing well phase B, adding thickener to water and making them swelling enough phase A, and then mixing A phase slowly to B phase, stirring the substrate until it became to be well-distributed, and then spreading it using the extrusion method. Finishing all the above steps, the substrate should be dried at room temperature. The optimum stirring speed is400r/min, The optimum mixing time is20min, And the optimum refining temperature is45℃4. Research on the quality evaluation of breviseapine cataplasmContent determination for the cataplasm was carried out by using high performance liquid chromatography (HPLC) method. We conducted experiments of paste content, adhesiveness,shape forming ability for cataplasm. The results showed that extract content and shape forming ability of the cataplasm are up to the first part of2010version of "Chinese pharmacopoeia". In addition, the amount of paste content to10.18g, the experiment of adhesiveness indicated that the cataplasm can bear no.13steel ball, the content of each affixed to scutellarin of not less than0.115g.5. The toxicity experiments of breviseapine cataplasmAccording to safe requirements of transdermal drug delivery experiment, we performed dermal irritation tests, dermal allergy tests, dermal toxicity tests of breviseapine cataplasm, the results showed that there is no irritative reaction, allergic reaction, toxic reaction. Therefore, breviseapine cataplasm could be regarded as a safe external preparation, could be long-term use.6. The pharmacokinetic experiments of breviseapine cataplasmThe pharmacokinetic characteristics of breviseapine cataplasm were explored by comparing the transdermal drug delivered breviseapine cataplasm with oral administrated pills. It showed that the peak time for cataplasm was7h, but4h for pills. What’s more, AUC of the former was1.39times higher than that of the latter. So, we drew the conclusion that the breviseapine cataplasm could keep the level of medication in blood constant longer, reduce the times of deliever, be easier to use.