【作者】 王曦；

【导师】 滕利荣； 逯家辉；

【作者基本信息】 吉林大学 ， 微生物与生化药学， 2010， 硕士

【摘要】 疼痛及炎症是许多疾病的伴随症状,鼠妇作为一味中药,其镇痛抗炎作用早已被报导过,民间也多有用鼠妇水煎物治疗风湿、癌症疼痛的先例。为了充分利用我国宝贵中药资源,将传统中医药资源与现代化生产工艺充分结合,本文在总结现有临床研究及民间用药研究的基础上,对鼠妇的提取工艺、安全性、药效学、制剂工艺、质量标准和稳定性进行了研究。研究中运用中心组合实验对鼠妇中镇痛抗炎成分的提取工艺进行了优化；确定了鼠妇镇痛片剂的制备工艺并建立了相关质量标准；通过对实验动物全身性用药的急性、长期毒性试验对鼠妇镇痛片剂的安全性了进行研究；采用镇痛、抗炎试验对片剂的主要药效学作用进行了研究；通过常温试验和加速试验对片剂的稳定性进行了考察,为今后的临床用药和生产实践提供了理论依据。更多还原

【Abstract】 Pain and inflammation are associated with concomitant symptom of many diseases, which bother countless patients in the world every year. At present, there are two major categories of analgesic widely used in clinic. One is nervous analgesic, which easily leads to addiction after a long-term continuous application. The other is a antalgic, antipyretic, and anti-inflammatory non-steroidal drug. Long-term use of this analgesic could easily causes adverse reactions to digestive and cardiovascular systems. Therefore, if we can develop a curative effect, less toxic side effects of analgesic drug for the treatment of pain will have a profound impact.Traditional Chinese medicine as our unique drug, the product of ancient Chinese working people, accumulated through long-term medical heritage is extremely rich and extremely valuable. It has been indicated that many aspects of Chinese medicine have anti-inflammatory analgesic efficacy and the side effects is quite small, which is confirmed by not only the test of long-term medical practice, but also by modern scientific researches.Armadillidiam Vulgare is the whole dried body of Latreille of Armadillidiiae, Arthropoda Crustacea. Its medicinal value was described as early as in the first existing pharmacy monograph "Shen Nong Ben Cao Jing", which recorded its function as acid, cold, and detoxifying, and the effect of removing bruises and analgesic activity. From the seventies of last century, the analgesic effect of Armadillidiam Vulgare was gradually concerned by people. A variety of academic journals reported its analgesic effect in alleviating of postoperative pain and cancer pain. Animal experiments have indicated that extracts of Armadillidium could significantly inhibite the writhing induced by acetic acid without causing addiction. Further studies showed that Armadillidiam Vulgare extracts contain mainly proteins, carbohydrates, and sterols.To take full advantage of our precious traditional Chinese medicine resources, in the premise of assurancing Chinese medical scientific theories and characteristics, features and advantages of clinical application, we should inherit and carry forward. In this paper, based on summary of the previous theoretical and experimental researches, and by using the advanced modern pharmaceutical science and technology, the extraction process of Armadillidiam Vulgare, pharmacodynamics and preparation process were studied. First, using response surface analysis Armadillidiam Vulgare Extraction of active ingredients conditions were optimized. Set three single factors:extraction solvent, extraction temperature and ratio of water; With the mouse acetic acid writhing test the analgesic effect of the extract to verify, according to single factor test results. According to Box-Benhnken the central composite experimental design theory, response surface method in the three factors and three levels on Armadillidiam Vulgare extraction conditions were optimized to determine the optimal extraction conditions:49.60%ethanol extraction solvent, extraction temperature of 88℃, ratio of liquid and materials (g/ml) 1:16, and the use of response surface analysis of various factors on the interaction between the analysis. Under these conditions, analgesia rate of extracts was 64.95 percent.Through the identification test, extracts were qualitatively identified. Test items include amino acids, peptides, proteins, sugars and glycosides, unsaturated terpenoids, iridoid, sterols and volatile oils, grease, triterpenes, flavonoids, alkaloids and anthraquinone. According to phenomenon of the trial judge, the extracts contain proteins, carbohydrates, unsaturated terpenes, sterols and volatile oils, grease and other ingredients.According to the nature of Armadillidiam Vulgare extract, set a different prescription to tablet appearance, tablet weight variation, hardness and disintegration time are evaluated, and screened in a variety of matrix types of tablets, matching, etc, and ultimately determine the prescription.Every 1000 tablets,filler:starch 146g、dextrin 219g; adhesive:60% PEG4000; disintegrating:PVPP25g; lubricants:magnesium stearate 2.5g、talcum powder 2.5g; sweeteners:xylitol 5g;drug loading:100g. Pressure piece of data:pressed the main pressure 8.8KN; tablet thickness of 4.2mm; pre-press thickness of 0.2mm; filling thickness of 0.2mm, validation experiments show that this process is stable.The establishment of quality standards were established,including armadillidiam Vulgare crude drug and analgesic tablets quality standards, for a total extract of sterol,we use Liebermann-Burchard colorimetric to obtained the total sterol content of extracts and Armadillidiam Vulgare analgesic tablets; Armadillidiam Vulgare analgesic tablet formulation for the character, identification, weight variation limits, disintegration test items, the results are in line with pharmacopoeia requirements. We use visible spectrophotometry to determine the Armadillidiam Vulgare of sterols, methodological study show that the method linearity, precision, reproducibility, and recovery were good, indicating that this method is accurate, effective, and can be applied to the preparation of quality control.Toxicity of the extracts was studied, including acute toxicity and long-term toxicity tests.In acute toxicity test, it failed to detect half of the lethal dose, so a maximum amount test was administrated, and showed that the maximum tolerated dose is 80g crude drug/kg. In the long-term toxicity test cycle, the animals didn’t show any toxic reaction or abnormal, indicating the toxicity of the analgesia tablets of Armadillidium is small, and safety to use. In the pharmacodynamic study, we use acetic acid writhing in mice, mouse hot plate and thermal stimulation in rats flick method to study the analgesic effect of extract. We found that extracts can inhibit the writhing caused by acetic acid, extend the mice licking time and rat tail flick time, and significantly increase the pain threshold in experimental animals. Anti-inflammatory tests using xylene induced ear edema and carrageenan induced rat paw edema test, showed that the tablets extracts can inhibit inflammation. But the inflammatory response is only the high dose group had significant anti-inflammatory effect,and the middle and low’dose group compared with the control group there was no significant difference.Finally, stability in the preparation, use of room temperature test and accelerated test. During the trial, respectively 0,1,2,3,6 months each sampling time, the stability of the tablet key study items include:character, determination, identification, inspection, Weight difference,hardness,melting time, dissolution and microbial limit.Sample study leave at room temperature for 6 months, accelerated test study after 6 months, each of these items were not detect a significant change, indicating that the quality of tablets stored in the study phase was stable.更多还原