CN1718218A - 一种治疗骨性关节炎的药物及其制备方法 - Google Patents
一种治疗骨性关节炎的药物及其制备方法 Download PDFInfo
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Abstract
本发明公开了一种治疗骨性关节炎(骨质增生症)寒湿阻络证的药物，它以扶芳藤、忍冬藤、淫羊藿、独活、穿山龙等五味药物原料制备而成，全方具有祛风除湿、散寒止痛、活血通络的作用，在用于治疗骨性关节炎寒湿阻络证所见的关节疼痛、冷痛沉重、活动受限、劳累后加重等症方面的疗效显著，对人体无毒副作用，具有较好的临床推广价值。
Description
所属技术领域
本发明属于医药品的制备技术领域，涉及一种以中草药为原料制备的用于治疗骨性关节炎(骨质增生症)寒湿阻络证的药物以及该药物的制备方法。
背景技术
骨性关节炎是人群中常见的关节疾病之一，多发于负重较大和活动较多的关节部位，如颈椎、腰椎、膝、髋等大关节，以膝骨关节炎最为多见。骨性关节炎发病与年龄有关，40岁以上的人群发病较多，且患病率随年龄的增长而增加。美国有关调查结果表明，38％的成人患有膝骨关节炎，成人症状性膝骨关节炎的年发病率为2‰。据我国对某些地区的调查结果显示，成人中膝骨关节炎患病率为25.5％，而在65岁以上的人群中则有超过50％的人患膝骨关节炎，可见本病是中老年人致残及生活质量下降的重要原因之一。
骨性关节炎可分为原发性骨性关节炎和继发性骨性关节炎，前者常因关节软骨退行性变性和关节慢性劳损所致，所以多发生于中年(40岁)之后；后者由于常继发于先天或后天畸形、关节劳损(如关节内骨折)以及其它关节疾病(如类风湿性关节炎)之后，所以也可发生在青壮年。无论原发性或是继发性，关节软骨的退行性病变是基本的病理改变，因此治疗手段是基本相同的。现代医学采用药物治疗骨性关节炎的手段主要包括：(1)、短期使用足剂量镇痛剂为首选方法，如乙酰氨基酚、右旋丙氧酚、可待因等，但次类药物因有一定的成瘾性，故不宜长期使用，另外前两类药物出现恶心、呕吐、眩晕和便秘的发生率较高；(2)、抗炎药，如吲哚美辛、阿司匹林、保太松等非甾类和得保松、利美达松等糖皮质激素类抗炎药，但非甾类和糖皮质类抗炎药对软骨基质的合成有抑制作用，长期使用会使骨性关节炎的基本病变反而加重；(3)、软骨保护剂，如透明质酸、过氧化物歧化酶、D-葡糖胺、葡糖胺聚糖、四环素族抗生素、S-腺苷基蛋氨酸、双磷酸盐类骨重吸收剂以及人工合成的基质金属蛋白酶抑制剂，这些药物的临床副作用小，但其属于慢性作用抗骨性关节炎药物，且大多未在临床广泛使用，疗效尚不能肯定。目前临床用于治疗骨性关节炎的中成药主要有骨刺片、骨仙片、骨刺消痛液、穿龙骨刺片、蠲痛片、骨痛宁、舒筋定痛散等均有一定疗效，且无明显副作用，但因其功效均主要为舒筋活络、活血止痛、补肾健骨，在对临床多见的骨性关节炎(骨质增生症)寒湿阻络证的治疗方面效果仍不理想。
发明内容
本发明的目的在于针对现有技术存在的问题，提供一种以中草药为原料制备的用于治疗骨性关节炎的高效药物以及该药物的制备方法。
本发明所述药物的制备方案是设计者根据多年临床实践并在现代药理学实验基础上通过悉心总结研制而获得的，它依据祖国医学关于驱风通络、活血化瘀、壮骨强筋、通痹止痛的治疗原则，通过将扶芳藤、忍冬藤、淫羊藿、独活、穿山龙等五味药物原料加以科学配制而成。
构成本发明所述药物之各组分原料的重量配比为
扶方藤 6～9 ，忍冬藤 3～4.5， 淫羊藿 2～3，
独活 2～3， 穿山龙 1～1.5。
本发明所述的药物是一种针对膝骨性关节炎(骨质增生症)临床多见寒湿阻络证而研制的行之有效的中药配方，其组方、功能及适应病症符合中医对痹证、骨痹的理法。方以扶芳藤为君药，补肾以壮骨强筋，活血以消瘀通络(《新华本草纲要》谓扶芳藤能“补肾强筋”，《浙江天目山药植志》谓其能“行气活血，治腰膝痛、关节酸痛”)；臣以忍冬藤助君药宣瘀通络(《医学真传》谓忍冬藤“乃宣通经脉之药也”，《履巉岩本草》谓其“治筋骨疼痛”)；淫羊藿助君药补肾壮骨、通气行血(《医学入门》谓淫羊藿能“补肾虚、助阳、坚筋壮骨”，《本草经疏》谓其“辛以润肾、甘温益阳气，温能通行气血”，《本草正义》谓其“温通气血，故能化凝结”)；佐以独活散寒驱湿，又助君药宣通经络(《本草经疏》日：“独活苦辛温，能辟风寒，邪散则气血疏通，故其痛自止也。......苦能燥湿、温能辟寒、辛能发散，寒湿去而肾脏安，百节痛已。”《本草正义》谓其“宣通百脉，调和经络，通筋骨，利关节”)；穿山龙助君药活血通络(《东北药植志》谓穿山龙“舒筋活血，治腰腿痛、筋骨麻木”)。全方君一、臣二、佐二，共奏祛风除湿、活血化瘀、消肿止痛、补肾强筋之功。该药的组方有以下特点：1、纵观诸多治疗骨性关节炎的中成药，无以扶芳藤、忍冬藤、独活入药者，而该方以扶芳藤为君，忍冬藤为臣，是其独到之处，且方仅五味药，而能对“虚、邪、瘀”并治，可谓处方精炼；2、该方以助阳之淫羊藿补肾，其意在于“温壮肾督阳气，阳盛则阴充，自可驱邪外出，也可御邪不致再侵......。”3、芳中独活其用有三：一是取其“祛风之品......多为辛散，能行能润，有胜湿散寒、使寒湿之邪从里外透、发越之功。”二是独活为“风药中之润品，用之无散血伤阴之弊”；三是独活“气味雄列、芳香四溢，风寒之邪痹于肌肉，着于关节者，非此雄列之味，不能达于经脉骨节之间。”故其又有引药直达病所之用。
上述用于治疗骨性关节炎(骨质增生症)寒湿阻络证的药物，可以制成药剂学上所说的多种剂型，如胶囊剂、片剂等。其片剂剂型的制备方法如下所述：将组方中各药材净制、切片后，取三分之一量独活粉碎成细粉，备用；取剩余量的独活粉碎成粗粉，将独活粗粉置回流提取罐中，加入85％的乙醇回流提取三次，第一次加3倍量85％的乙醇，第二、三次各加2倍量85％的乙醇，各回流提取3小时，合并提取液，滤过，滤液减压(0.07MPa，50℃)回收乙醇后，收集提取液备用；另取组方量的扶方藤、忍冬藤、淫羊藿、穿山龙四味药物原料加水煎煮两次，第一次加12倍量水，煎煮2小时，第二次加8倍量水，煎煮1小时，滤过，滤液与上述独活提取液合并，减压(0.08MPa，60℃)浓缩至相对密度为1.35～1.40(60℃测)的稠膏，加入上述独活细粉，混匀，减压(0.08MPa，65℃)干燥，粉碎成细粉，用80％乙醇适量，14目筛制粒，65℃干燥，12目筛整粒，加入3％硬脂酸镁，混匀，以10mm深弧冲模压片，即制得该药物片剂。
在本发明研制过程中，为证明该药物的治疗效果及安全性，设计者对根据上述制备方法得到的片剂进行了药效学、毒理学和临床方面的试验研究，其试验研究结果如下。
一、与功能主治有关的药效学研究
经对本发明片剂试验结果表明，该药4.2g/kg和8.4g/kg两个剂量组对鲜蛋致炎小鼠引起的足跖肿胀有显著抑制作用(P＜0.01)，对大鼠琼脂引起踝关节肿胀有明显的对抗作用(P＜0.05或P＜0.01)，对大鼠棉球肉芽肿有显著的抑制作用(P＜0.01)，表明本发明片剂有显著的抗炎作用.该药的4.2g/kg和8.4g/kg剂量对小鼠电刺激法、热板法致痛反应有显著的提高痛阈的作用(P＜0.01)，对大鼠甲醛致痛反应有一定的镇痛作用(P＜0.05或P＜0.01)，表明本发明片剂具有一定的镇痛作用，且镇痛作用随剂量增加而增强。该药大、中、小(4.5g/kg、9g/kg、18g/kg)三个剂量组对大鼠佐剂性关节炎有显著的抑制作用(P＜0.05或P＜0.01)，说明本发明片剂对大鼠佐剂性关节炎继发病有一定的抑制作用。该药对小鼠、大鼠体重、胸腺、脾脏重量虽无明显影响，但却能显著促进腹腔巨噬细胞吞噬功能，又能增加单核吞噬细胞系统廓清功能，表明本发明片剂抗炎作用可能和调节非特异性免疫功能有关。该药同时对血小板血栓形成有抑制作用，可使大鼠血液流变学指标改善，血粘度降低，红细胞电泳速率加快，纤维蛋白原降低，表明本发明片剂具有多种药理作用。
二、毒理研究
由陕西中药研究所对本发明片剂所做的急性毒性试验表明：昆明种小鼠及SD品系大鼠灌胃给药得该药的最大给药量为60g生药/kg，以体重折算该剂量约为临床拟定成人日用量的111倍。
由陕西中药研究所等对本发明片剂所做的长期毒性试验表明：对SD大白鼠三个月时间灌胃给药得该药的最大剂量为4.8g/kg(37.8g生药/kg)，约相当于临床成人每日用量的70倍。动物的一般状况、血液学、血液生化学、心电图均无异常，系统解剖、脏器系数及组织病理学检查也未发现异常病理改变。停药30天也未见异常。
三、临床研究
本发明所述药物主要用于治疗膝骨关节炎(膝OA)寒湿阻络证。根据卫生部药政局(94)ZL-22号文件，观察本发明片剂治疗膝骨关节炎的疗效及安全性。该项临床试验研究工作分别在中国中医研究院广安门医院、山东中医药大学附属医院、陕西省中医药研究院附属医院、西安医科大学第二临床医院(现西安交大第二医院)、陕西省人民医院五家单位进行，该项临床试验研究依据《中药新药临床研究指导原则》制定的膝骨关节炎的诊断标准、寒湿阻络证的辨证标准、疗效检测指标及疗效评定标准，试验疗程为四周，采用随机盲法分治疗组和对照组，治疗组每日3次服本发明胶囊剂，每次6片(每片重0.25g重)，治疗组使用本发明片剂观察了300例，其中显效以上137例，显效率为45.67％，有效132例，有效率为44％，总有效率为89.67％；对照组使用穿龙骨刺片观察150例患者，其中显效以上59例，显效率为39.33％，有效58例，有效率为38.67％，总有效率为75％，两组疗效经统计学处理P＜0.05，有显著性差异，说明本发明片剂具有散寒除湿、通络止痛的作用，治疗膝骨关节炎的疗效优于对照组药物。本发明片剂治疗膝骨关节炎的的临床症状如关节疼痛(夜间休患疼痛、行走时疼痛)、晨僵、关节冷痛、沉重等均有较好的疗效，可以明显改善这些症状，特别是对于膝关节的冷痛的疗效明显优于对照组，具有统计学意义。因为疼痛是膝骨关节炎的主要临床表现，所以该项临床试验采用了国际上沿用的标尺法测定治疗前后膝关节疼痛的变化。结果表明，治疗后标尺法分值较治疗前有明显的降低，经统计学处理P＜0.01，亦有非常显著性的差异，说明本发明片剂有较好的止痛作用。该项临床试验还对膝骨关节炎患者使用本发明片剂后临床体征的变化进行了总结，结果表明本发明片剂能改善膝骨关节炎的临床体征，其压髌试验、浮髌试验及压痛的消失率分别为41.77％、40.9％及46％。在该项临床试验进行期间，使用本发明片剂有5例患者出现胃部不适的症状，出现率为1.67％，这与本药的某一成分对胃粘膜有刺激有关，改为饭后服用即无此不良反应。余未见其它临床不良反应。经血、尿、便常规及心电图、肝功、肾功能检测说明本发明片剂对血、尿、便常规及心、肝、肾功能均无不良影响，使用安全可靠。
Claims (3)
1、一种治疗骨性关节炎的药物，其特征在于它是由下述重量配比的中药药物原料制成的药剂
扶方藤6～9，忍冬藤3～4.5，淫羊藿2～3，
独 活2～3，穿山龙1～1.5。
2、根据权利要求1所述的治疗骨性关节炎的药物，其特征在于所述的药剂是胶囊剂或片剂。
3、一种用于制备权利要求2所述药物片剂的方法，其特征在于将组方中各味药材净制、切片后，取三分之一量独活粉碎成细粉，备用；取剩余量的独活粉碎成粗粉，将独活粗粉置回流提取罐中，加入85％的乙醇回流提取三次，第一次加3倍量85％的乙醇，第二、三次各加2倍量85％的乙醇，各回流提取3小时，合并提取液，滤过，滤液减压(0.07MPa，50℃)回收乙醇后，收集提取液备用；另取组方量的扶方藤、忍冬藤、淫羊藿、穿山龙四味药物原料加水煎煮二次，第一次加12倍量水，煎煮2小时，第二次加8倍量水，煎煮1小时，滤过，滤液与上述独活提取液合并，减压(0.08MPa，60℃)浓缩至相对密度为1.35～1.40(60℃测)的稠膏，加入上述独活细粉，混匀，减压(0.08MPa，65℃)干燥，粉碎成细粉，用80％乙醇适量，14目筛制粒，65℃干燥，12目筛整粒，加入3％硬脂酸镁，混匀，以10mm深弧冲模压片，即制得该药物片剂。
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102441088A (zh) * | 2011-11-30 | 2012-05-09 | 宋爱民 | 治疗腰肌纤维炎的中药酒剂 |
| CN104524190A (zh) * | 2015-01-06 | 2015-04-22 | 王国徽 | 治疗风湿性腰椎病患的药剂及制备方法 |
| CN104547581A (zh) * | 2015-01-06 | 2015-04-29 | 王国徽 | 风湿性腰椎病疏风散寒药酒及制备方法 |
| CN108210682A (zh) * | 2018-02-27 | 2018-06-29 | 黄建民 | 一种治疗骨性关节炎的活血药泥及制备方法 |
| CN114949098A (zh) * | 2022-03-28 | 2022-08-30 | 江苏莹华生物制药有限公司 | 一种治疗骨关节炎的中药缓释凝胶剂及其制备方法 |
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| CN1366948A (zh) * | 2001-01-20 | 2002-09-04 | 杨孟君 | 纳米复方扶芳藤制剂药物及其制备方法 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102441088A (zh) * | 2011-11-30 | 2012-05-09 | 宋爱民 | 治疗腰肌纤维炎的中药酒剂 |
| CN102441088B (zh) * | 2011-11-30 | 2014-04-02 | 宋爱民 | 治疗腰肌纤维炎的中药酒剂 |
| CN104524190A (zh) * | 2015-01-06 | 2015-04-22 | 王国徽 | 治疗风湿性腰椎病患的药剂及制备方法 |
| CN104547581A (zh) * | 2015-01-06 | 2015-04-29 | 王国徽 | 风湿性腰椎病疏风散寒药酒及制备方法 |
| CN108210682A (zh) * | 2018-02-27 | 2018-06-29 | 黄建民 | 一种治疗骨性关节炎的活血药泥及制备方法 |
| CN114949098A (zh) * | 2022-03-28 | 2022-08-30 | 江苏莹华生物制药有限公司 | 一种治疗骨关节炎的中药缓释凝胶剂及其制备方法 |
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