The Pharmaceutical Research Of Anti-inflammatory Sore Ointment

Ulcers anti-inflammatory ointment , a kind of natural medicine used for topical preparations,was made by the processing of the medicinal materials- lithospermum extraction and ripe rhubarb extraction, mainly for the injury skin epidermis wound debaucjed,fungal infection and chronic skin ulcers. According to the technology guiding principles of traditional Chinese medicine and natural medicine's sixth class of new medicine research in the《Drug registration management approach》promulgated by national food and drug administration,we conducted the experimental study of pharmacy part before being used for practicing to the preparations,applying the modern pharmaceutical technology. And the concrete content includes the following several parts:1 Medicinal material pretreatment research1.1 The extraction separation technology of total naphthalene quinone in lithospermum and extraction's quality standard researchThe test had done the comparative study on the traditional solvent extraction and new technology CO₂ supercritical fluid extraction. Because the method of CO₂ supercritical fluid extraction has the advantages of extraction of high purity, good extraction, and extractions having no residual organic solvent, etc., it could improve the efficacy of the preparation.While its non-irritating to the sore side, it was in line with the needs of the disease treatment with the preparation. In addition, constituents of the total naphthalene quinone in lithospermum had the thermal instability,so when the temperature exceeded 60℃, its content decreased, while the CO₂ supercritical fluid extraction was with a low operating temperature, composition not destroyed and so on. In summary, the final determination was to use the method of CO₂ supercritical fluid extraction .Using orthogonal test method,the extraction pressure, extraction temperature and extraction time were optimized.The total active ingredients in naphtho quinoneβ,β'- dimethylacrylshikonin being as index,using the content of extractions by high performance liquid chromatography,we determined the total naphthoquinone shikonin optimum extraction: Extraction temperature was 40℃, extraction pressure was 30MPa, extraction time was 120 minutes. Accordance with the "Chinese Pharmacopoeia" Pharmacopoeia 2010 edition of aChinese herbal extract of the relevant checks, the total shikonin naphthoquinonesestablished quality standards, the total shikonin naphthoquinones conducted a quality analysis, including characte -r, loss on drying, ignition Residues, heavy metals other items, by their thin-layer chromato- graphy for qualitative analysis, usinghigh performance liquid chromatography method for its quantitative analysis, and developed a minimum of the examinations. The results show that using thisprocess extracts high purity and low impurities, and has a low temperature, non- toxic, environmental protection, etc., for promotion and to enlarge production.1.2 The extraction separation technology of total rhubarb extraction and extraction's quality standard researchIn this experiment we adopted high concentrations of ethanol extraction, and acid-base separation to separate total rhubarb anthraquinones,then purified by macroporous resin. First, we used a single factor test method to investigate the medicinal particle size, extraction technology and extraction solvent preliminary; Then we used the orthogonal experiment method to optimize the amount of solvent, extraction times and extraction time so as to determine the best rhubarb extraction process: simple reflux, herbal particle size were over 60 mesh, extraction solvent was 70% ethanol, the solvent was 8 times the weight of herbs, the extraction time is 60 minutes, extraction times was 3 times. Comprehensive use of porous resin and acid-base separation was to purify the components in total macroanthraquinone of rhubarb,to determine the process parameters: 75% ethanol, add hydrochloric acid to pH = 1.0.Accordance with the "Chinese Pharmacopoeia" Pharmacopoeia 2010 edition of aChinese herbal extract of the relevant checks, the establishment of Rhubarb qualitystandards,Rhubarb was the quality of analysis, including character, loss on drying, total ash other items By its TLC qualitative analysis by ultraviolet spectrophotometry of their quantitative analysis, and developed a minimum of the examinations. The results show that the extraction rate by this process, extractpurity, suitable for industrial production.2 Preparation research of ulcers anti-inflammatory ointmentScreening common cream base,propylene glycol, emulsifiers, liquid paraffin, lanolin, preservatives and other accessories, also using the ointment's appearance, painted malleability and consistency as index, Through the cumulative permeation amount of transdermal absorption, we screened promoting absorbent and the amount of using,and initially identified the types of materials, dosage range. Using Box-Behnken response design we optimized the ratio of the amount of the stearic acid, propylene glycol and laurocapramum in the cream prescription. Using the amount of 8-hour cumulative permeation of transdermal absorption of the active ingredientβ,β'-dimethylacrylshikonin in the lithospermum total naphtho quinone as index,and using Design Expert 7.1.6 software to conduct multiple regression to the test data, so as to ultiple regression model derived. According to mathematical models we described the response surface map, finally the optimum formulation and process parameters appeared: The amount of stearic acid is 29.03%, the amount of propylene glycol is 6.88%, the amount of laurocapramum is 2.73%. In order to make sure that industrial production can accurately feed, it was determined that the amount of stearic acid was 29%, the amount of propylene glycol was 7%, the amount of laurocapramum was 3%. Finalize the preparation process: stearic acid, lanolin, liquid paraffin as the oil phase, 60℃water bath allows the dissolved; The propylene glycol,laurocapramum, triethanolamine, ethylparaben was dissolved in the water as the water phase,and through the water bath to heat them to the same temperature. Finally mixed and stired the two to condensation, then separate packaging.3 Experimental study of allergic and hemolyticThe experimental observation was the allergic reaction of rabbit skin, and then made the severity of erythema and edema as index, conducted the allergic pilot study about the ulcers anti-inflammatory ointment.The results showed that: no skin allergic reaction happened on rabbits after being daubed repeatly with ulcers anti-inflammatory ointment, and the comparison was made with the positive drug 2,4 - dinitro chloro benzene, acetone solution, indicating that the agents had no evident allergic reaction. We adopted the ways of observation and UV spectrophotometry to monitor the hemolytic circumstances of the red blood cell in the rabbits'blood after daubing ulcers anti-inflammatory ointment.With distilled water as a positive control, hemolytic rate of preparation was calculated. The results showed that: the hemolytic rate of preparation was less than 5%, no significant hemolytic situation, and indicating that the preparation was safe so that it laid the foundation for further study. 4 The study of quality standards of preparationIn the precondition that the preparation prescription and preparation technology were stable the quality standards of ulcers anti-inflammatory ointment were established,including character, identification, inspection (size, quantity of contents, pH, sterility, microbial limits), determination and so on, to reflect and control the quality of the preparation.Through the above experimental researches of pharmacy part before being used for practicing on ulcers anti-inflammatory ointment, we got the ulcers anti-inflammatory ointment with stable preparation process, non-allergic and non-hemolytic, also with quality controlled, that will be the basis for further study on pharmacodynamics and toxicology research.