Study On The Preparation Of Gui-Shao Cataplasm

Gui-shao formula has been used for the IBS treatment in clinic for many years in digestive department, Jiangsu Province Hospital of Integratied of Chinese and Western Medicine. The prescription consists of Cinnamomi Cortex, Paeoniae Radix Alba, Asari Radix et Rhizoma, Angelicae Dahuricae Radix, etc. It has the efficiency of soothing liver and strengthening spleen, dispelling cold to relieve pain. The clinical usage of the prescription is to mix all the medicinal materials together, grind into powder, and then apply to the skin of umbilical part after condensing to dense ointment with vinegar 5%.Since this method is extremely inconvenient to use, it is necessary to make it into moderate dosage form. Modern extraction techniques, purification techniques and molding techniques were adopted in the research of Gui-Shao cataplasm, and quality control methods of the cataplasm were established. The research contents are as follows:1 Study on the transdermal material basicThis research was completed to analyze and identify the transdermal chemical components in Gui-Shao cataplasm by UPLC-Q-TOF-MS which was depended on the precise molecular weight peaks in the mass spectrum, the fragmentation information,mass spectrometry fragmentation patterns. The results indicated that 39 compounds were identified of which 16 peaks come from paeoniae radix alba, two peaks come from cinnamon, 13 peaks from Angelica, 6 peaks from dried ginger, two peaks from Radix Aucklandiae, all of the components included monoterpene glycosides, phenyl propanoids, diphenyl heptanes, gingerol, terpene lactones etc. This study laid a foundation for the study of preparation process and quality evaluation.2 Study on process of extraction and purificationAccording to the physical and chemical properties and pharmacological actions of transdermal compositions, we designed a multiple extraction technology which wasused to extract active components. To optimize the best extraction technical condition of volatile oil by making the yield of volatile oil as indictors, we studied the factors that influence the extraction of volatile oil: the time of immersion, the amount of water, the time of extraction. The content of paeoniflorin and water-soluble extracts were used as comprehensive evaluation indexes, orthogonal test was used to optimize extraction process with the amount of water, decocting time and decocting times as factors. The best extraction technical condition of volatile oil: added in 8 times the amount of water,immersed 2 hours, extracted 5 hours, the average yield of volatile oil in this condition was 0.86%. Optimum water extraction process was as follows: extracted 2 times with10 times the amount of water, 1.5 hours each time, average extraction amount of paeoniflorin was 3.58 mg·g-1 with RSD of 1.6%, and average content of water-solube extracts was 13.35% with RSD of 1.5%.This optimized extraction process can ensure effective ingredient saved to the maximum. The experiment result can provide basic and instruction data for the ascertainment of extraction technology of the Gui-Shao cataplasm recipe.The purification process of the water extract was investigated. Single-factor test was used to optimize the effect of purification in different alcohol concentrations with the transfer rate of paeoniflorin and the rate of removing impurity as the investigating index. Optimum alcohol precipitation process was: concentrated extraction liquid to its relative density was 1.10(70°C), added alcohol until the concentration of ethanol at80%, stilled 24 h. In this process the transfer rate of index component reached 95.22%and the impurity removal rate was 53.05%. Due to the complexity of the prescription's Chemical Constituents, in the scale-up production, it was found that when the concentrated solution reached to its relative density 1.15(70°C) after purificating and cooling was easy to caking, unease to be dried, and unease to grinde after decompression drying, which brought much difficulties in preparation processes, so it is not suitable to have alcohol precipitation process so as to remove impurity in industrial production.3 Study on preparation of Gui-Shao cataplasmThe objective of the present study was to establish a comprehensive evaluation method based on principal component analysis(PCA) for the study of multiple indexes of Chinese medicine, and to choose the best preparation technology of Gui-Shao cataplasm with this method. The appearance description, initial bonding strength,endurance bonding strength, and peel strength were taken as indexes, the total factor scores were calculated using PCA and were employed to evaluate the quality of Gui-Shao cataplasm, the uniform design test was used to optimize the amounts of sodium polyacrylate NP-700, aluminium glycinate, glycerin etc. for the Gui-Shao cataplasm. The optimal ratio of the prescription was as follows: sodium polyacrylate:NP-700?PVP K-30?aluminium?glycinate?EDTA-2Na?tartaric acid?glycerin?extract(8?1?0.25?0.07?0.15?25?20). The foremost factors were tartaric acid, PVP K-30,sodium polyacrylate NP-700, aluminium glycinate, glycerin, EDTA-2Na. The optimal prescription has uniform paste, easy ductility, moderate adhesion, it can provide the foundation for the development of new prescription of Gui-Shao cataplasm; and the principal component analysis can be a reference for the Chinese medicine research of multiple indexes.4 Percutaneous Permeability in vitro of Gui-Shao cataplasmThe study established a method to measure the amount of paeoniflorin after getting transdermal test in vitro and to explore the best amounts of azone(0%?1%?3%?5%) as transdermal penetration enhancers, the Q-t equation and penetrating skin velocity were respectively: Q=0.171 t+0.604, 0.171 ?g·cm-2·h-1; Q=0.365 t+0.002, 0.365 ?g·cm-2·h-1;Q=0.477 t+0.167, 0.477 ?g·cm-2·h-1; Q=0.420 t+0.079, 0.420 ?g·cm-2·h-1.When the amounts of azone was 3%, penetrating skin velocity could reach the maximum, so the optimal concentration of azone is 3%.5 Study on quality evaluationIn the study, preliminary quality researches were studied. Qualitative methods ofcinnamomi cortex, paeoniae radix alba, asari radix et rhizoma, angelicae dahuricae radix,and borneolum syntheticum were established. Quantitative methods of paeoniflorin, and cinnamaldehyde by HPLC were established in quantitative study. Analysis methods above were proved to have simple operation, be accurate, the precision, stability and reproducibility were fine. According to the determination results of three batches products, we temporary prescribe that the content of paeoniflorin shall not be less than0.250 mg per gram, the content of cinnamaldehyde shall not be less than 0.341 mg per gram. The conventional examination of cataplasm such as the content of plasters,forming property and adhesive ability were studied according to Chinese Pharmacopoeia, and all the results were in conformity with the requirements of Chinese Pharmacopoeia.In a word, the study of transdermal material base in vitro was carried out, and the parameters of extraction and molding techniques were optimized in this research.Besides these, quality evaluation system of cataplasm was formulated. This study provide an experimental basis for making the prescription to be a modern traditional Chinese medicine preparation, which can be carried and used conveniently, and has technically feasible and quality controllable.