| The symptoms of Rheumatic diseases are arthralgia and myalgia. The cause has not yet been elucidated up to now. The drugs for rheumatic diseases include NSAIDs, biological agents and Chinese patent medicine, in current. Because the Chinese patent medicine for the therapy of rheumatic diseases have several advantages, such as multiple effects (including anti-inflammatory, analgesia and immunoregulation) and little adverse effect, therefore, it is more suitable for long-term use.The wine of sea snake has been used to treat rheumatic diseases in the folk for a long time. Modern pharmacological studies have shown that the ethanol extract of sea snake has good effect on not only collagen induced arthritis (CIA) but also Freund's complete adjuvant induced arthritis (AA) in rats. The sea snake injection has been applied for clinical therapy in Beihai people hospital in Guangxi province for many years and the therapeutic effect is remarkable. However, injection treatment is inconvenience and has poor compliance of the patients. Therefore, this study aims to develop an oral anti-rheumatism drug named Haishe Fengshi Capsule, investigate the extraction and preparation process, establish the quality standards, investigate long-term stability and do the main anti-rheumatism pharmcodynamics research of Haishe Fengshi Capsule.With the evaluation of the total score of steroid content and the yield of dry extract, the extraction parameters, such as ethanol concentration, solvent volume, extraction duration and extraction times, were investigated through single-factor and L9(34) orthogonal experiments. The optimum process was adding 10 times of 75% ethanol into the crude medicine, refluxing for 1.0 h and extracting for three times.The preparation process of Haishe Fengshi Capsule was investigated by the determination of angle of repose and bulk density. The result showed that the optimal preparation process was as follows:the extract was filtered immediately, concentrated to relative density 1.2-1.3 (60?) by vacuum, added 0.8 times starch and microcrystalline cellulose (1:1), fully mixed, dried and crushed, then soft material was made by 85% ethanol, pelletized through 20 mesh sieve, dried under 60? and filled into NO.1 capsules.The quality standard for Haishe Fengshi Capsule was investigated in this dissertation. Lapemis handwickii, Litsea cubeba.root and Angelica sinensis in Haishe Fengshi Capsules were identified by thin-layer chromatograpy (TLC). The content of steroid were determined by the vanillin-sulfuric acid colorimetric method. The calibration curve for steroid showed good linearity within the concentration ranges of 0.005-0.025 mg/mL (r=0.9991), the average recovery was 95.60%, RSD=2.55%(n=9). The ferulic acid were determined by HPLC. Calibration curve was linear over the range from 0.5-30.0?g/mL with correlation coefficients of 0.9998 for ferulic acid. The average recovery was 96.46%, RSD=0.81%(n=9). The heavy metals, arsenic salt and microbial limit inspection were conducted referring to Chinese Pharmacopoeia 2015. The contents of heavy metal and arsenic salt were less than 20 and 2 ppm, respectively. The numbers of fungus, yeast and bacteria were in conformity with the criterion. Besides, E.coil was not detected. The developed method was accurate and reliable, therefore can be used as the quality control of Haishe Fengshi Capsule. The quality standard was established and the 12 months long term stability was investigated.The SD rats arthritis was induced by intraplantar injection of Freund's complete adjuvant (CFA) in the right hind paw. With the evaluation of Paw edema, the effect of Haishe Fengshi Capsule on the primary symptom and secondary symptom were investigated. The result showed that all dosage groups of Haishe Fengshi Capsule could ease the primary symptom (P<0.05), and both of high and low dosages could ease the secondary symptom significantly. The HE representative pathological section of right hind paw joints of rats showed that Haishe Fengshi Capsule relieved the symptoms of joints significantly. |
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