硫酸氨基葡萄糖氯化钾的制备及对大鼠骨关节炎模型的治疗作用  

Preparation of Glucosamine Sulfate Potassium Chloride and Its Therapeutic Efect on Rat Osteoarthritis Model

作　　者：李明皓[1] 江慧星[2] 沈妙根 彭秀兰 马彪 张军 姜红玲 王莹[4] 

机构地区：[1]中国药科大学理学院物理化学教研室,江苏南京210009 [2]南京中医药大学第一临床医学院,江苏南京210000 [3]江苏双林海洋生物药业有限公司,江苏南通226000 [4]中国药科大学生命科学与技术学院,江苏南京210009

出　　处：《药学进展》2013年第11期585-590,共6页Progress in Pharmaceutical Sciences

摘　　要：目的：制备硫酸氨基葡萄糖氯化钾,考察其对大鼠骨关节炎模型的治疗作用。方法：以甲壳素为原料,经盐酸水解得盐酸氨基葡萄糖,将其与硫酸钾置于水溶液中,通过充分的离子交换反应,并加入作为沉淀剂的有机溶剂,制备硫酸氨基葡萄糖氯化钾;考察反应温度、反应溶液中各离子平衡时间、反应原料配比以及沉淀剂的种类、加入量和加入时间等对最终产物的影响,优化制备工艺。建立木瓜蛋白酶诱导的大鼠骨关节炎模型,并灌胃给予硫酸氨基葡萄糖氯化钾,通过血清中丙二醛和一氧化氮含量测定、关节肿胀度观察和关节软骨病理切片检查,考察硫酸氨基葡萄糖氯化钾对模型大鼠骨关节损伤的保护作用。结果：确立优化的硫酸氨基葡萄糖氯化钾制备工艺：反应温度为45~55℃,离子平衡时间为0.5 h,盐酸氨基葡萄糖与硫酸钾的质量配比为22.5：7.15,作为沉淀剂的乙醇加入浓度约为75%及加入时间为3 h。骨关节炎模型大鼠接受硫酸氨基葡萄糖氯化钾给药后,血清中丙二醛和一氧化氮含量显著降低（P〈0.05或P〈0.01）,关节肿胀度明显减轻（P〈0.01）,且病理切片显示,仅有少许关节软骨细胞轻度变性,软骨未见明显坏死,细胞未见明显增生。结论：优化的硫酸氨基葡萄糖氯化钾制备工艺适用于工业化生产;硫酸氨基葡萄糖氯化钾对骨关节炎损伤具有显著保护作用,且效果好于盐酸氨基葡萄糖。To prepare glucosamine sulfate potassium chloride（GS） and to investigate its therapeutie effect on rat ostcoarthritis model Using chitin as raw material, glucosamine hydroehloride（Gtl） was ol）tamed via hydrolysis with hydrochloric acid. Then GS was prepared through ion exchange reaction of GH with potassium sulphate and addition of a organic snlvent as the precipitant in aqueous solution. The preparation technique was optimized by investigating the influences from the reaction temperature, the inn balance time in reaction solution, the ratio of reactants and the type, addition amount and addition time of the precipitant on the end product. The papain -induced rat osteoarthritis model was made and administrated intragastrically with GS. The protective effect of GS against articular cartilage damage was investigated by the determination of serum malondialdehyde （MDA） and nitric oxide （NO）, the observation of joint swelling and the pathological biopsy of articular cartilage in the rat model. The optimized preparation technique for GS included a reaction temperature of 4.5-55℃ , a ion balance time of 0.5 h, a mass ratio of 22.5：7.15 for GH and potassium sulphate and a addition concentration of approximately 75% and a addition time of ：/ h for ethanol as the precipitant. After intragastric administration of GS, the serum MDA and NO levels were significantly decreased （P〈0.05 or P〈0.Ol）, the joint swelling was significantly reduced （P〈O.Ol） and little cartilage cells with mild degeneration, cartilage with no obvious necrosis and cells with no marked hyperplasia were seen microscopically m the papain -induced rat osteoarthritis model. Conclusion： The optimized preparation technique for GS is practicable for industrial production. GS has a significant protective effect against OA-induced articular cartilage damage and is superior to GH in the effect.

关 键 词：硫酸氨基葡萄糖氯化钾 制备工艺 骨关节炎 动物模型 治疗作用 

分 类 号：R96[医药卫生—药理学]