CN1561994A治疗类风湿性关节炎和免疫性疾病的含青蒿提取物药物组合物---双氢青蒿素，青蒿琥酯，蒿甲醚，蒿甲醚等)的药物组合物|CN1561994A Medicinal composition containing Artemisia extract for treating rheumatoid arthritis and immune-related diseases---a medicinal composition comprising dihydroartemisinin, artemet
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CN1561994A治疗类风湿性关节炎和免疫性疾病的含青蒿提取物药物组合物---双氢青蒿素，青蒿琥酯，蒿甲醚，蒿甲醚等)的药物组合物
CN1561994A Medicinal composition containing Artemisia extract for treating rheumatoid arthritis and immune-related diseases---a medicinal composition comprising dihydroartemisinin, artemether, arteether, etc
治疗类风湿性关节炎和免疫性疾病的含青蒿提取物药物组合物
本发明涉及一种用于治疗类风湿性关节类和自身免疫性疾病伴关节炎症状的药物，治疗类风湿性关节类和免疫性疾病的含青蒿提取物(双氢青蒿素，青蒿琥酯，蒿甲醚，蒿甲醚等)的药物组合物。该组合物中青蒿素或青蒿素衍生物的含量为1~99％。该药物组合物含有青蒿素或青蒿素衍生物的有效剂量为20~200mg/日。可以为任何常用的药物形式，如：固体制剂，流体，或膏状等。
治疗类风湿性关节类和免疫性疾病的含青蒿提取物药物组合物
技术领域：
本发明涉及一种用于治疗类风湿性关节类和自身免疫性疾病伴关节炎症状的药物，特别是用于治疗类风湿性关节炎和自身免疫性疾病伴关节炎症状的含有青蒿素或青蒿素衍生物(双氢青蒿素，青蒿琥酯，蒿甲醚，蒿甲醚等)的药物组合物。
背景技术：
类风湿性关节炎(以下简称RA)是自身免疫性疾病的一种，是一种世界范围内的原因不明的全身性自身免疫性疾病，其发病率0.4～1％，其主要特征是以慢性，对称性及末梢关节弥漫性滑膜炎、末期出现各种程度的进行性关节破坏，变性及关节功能丧失，严重地影响着患者的劳动及生活能力，给社会造成巨大的负担。而其他的自身免疫性疾病也通常伴有相类似的关节症状，对该类疾病的治疗尚没有特效药物，多采用非甾类消炎镇痛剂及免疫抑制剂治疗，不但不能完全控制病情，且有较大的毒付作用。
近年来中医药对类风湿性关节炎及自身免疫性疾病研究受到国内外专家及患者的重视，开发了一些治疗RA的药物，例如：中国专利申请02137816公开了一种RA的治疗药物组合物，其中含有中药成份：赤茯苓12％，当归12％，地肤子12％，五加皮10％，枇杷叶10％，海桐皮9％，白薇9％，黄芩8％，川黄连7％，广藿香6％，木通5％。再如中国专利申请01117709公开了一种治疗类风湿性关节炎的药物，它是以何首乌、党参、当归、黄芪、黄精、白术、狗脊、全蝎、乌梢蛇、地龙、蚂蚁、丹参、桑枝、桂枝、苍术、羌活、独活、防风、秦艽、桑寄生、杜仲、川牛膝、黄柏、千年健、钻地枫、乳香、没药、青风藤、天南星、鸡血藤、桑葚子、元胡、川芎、枣仁、知母、茯苓、草乌、川乌、仙灵脾、红花、续断、丹皮、忍冬藤、赤芍、薏苡仁、海桐皮、络石藤、甘草为原料，根据每味中药的不同特性，针对类风湿性关节炎的不同症状，按比例配制成基本药剂、寒甚或热甚者相适应的药剂。
上述这些中药组合物一般都是中药的常规用药，使用时医生还必须根据中医辨证论治的原则按照患者的情况进行组方；也有一些中成药成分较多，制备复杂，实际应用还不能完全满足临床医生及患者的需要。
青蒿素是我国学者自主开发且被国际公认的中药提取物，青蒿素及其衍生物是一类有效的抗疟药和抗疟药物组合物。系从我国中药黄花蒿中提取的有效单体成分，已被世界卫生组织推荐为抗疟疾新药。近年来随着国家及各研究单位对青蒿素研究的继续深入，开发了一些以青蒿素为主要成分的新的复方制剂的抗疟剂，如：中国专利申请00113134公开了一种治疗疟疾的复方制剂；同时还不断发现了在其他新领域中的应用，如：中国专利申请99103346公开了一种治疗红斑狼疮和光敏性疾病的含双氢青蒿素的药物组合物等。现有文献报道可以将青蒿油搽剂应用于癣病的治疗，通过对青蒿素的体外抗真菌作用的研究，证实青蒿素的抗菌普及作用与目前常用的广谱抗真菌药酮康唑相似，且对某些真菌的作用强于酮康唑，即其抗真菌作用效果良好。
发明内容：
本发明的目的，是提供一种安全有效的治疗类风湿性关节类和免疫性疾病的含青蒿提取物药物组合物。
本发明的技术方案如下。
一种治疗类风湿性关节炎和免疫性疾病的含青蒿提取物药物组合物，为含有有效剂量的青蒿素或青蒿素衍生物的药物组合物。
所述的蒿素衍生物包括双氢青蒿素，青蒿琥酯，蒿甲醚和蒿甲醚。
该组合物中青蒿素或青蒿素衍生物的含量为1～99％。
所述的药物组合物含有青蒿素或青蒿素衍生物的有效剂量为20～200mg/日。
该药物组合物可以单独使用，也可以与现有治疗RA和自身免疫性疾病的其他药物联合使用。
所述的药物组合物为可以是任何常用的药物形式，如：固体制剂，流体，或膏状等。
本发明是基于这样的事实完成的。本案发明人在长期的临床治疗RA和自身免疫性疾病及各种关节炎的过程中发现中药青蒿具有较好的清热解毒，消肿，止痛功效。而青蒿素又是我国自70年代开始研究的中药一类新药，为此我们在免疫和自身免疫性疾病方面对青蒿素或其衍生物以及含青蒿素的药物组合物进行了研究，表明青蒿素在具有免疫调节的基础上，从药效学及临床研究均证明青蒿素或青蒿素衍生物对RA和自身免疫性疾病伴关节症状的具有较好的疗效，具有消炎、镇痛、免疫调节的疗效。且具有见效快，无明显的毒副作用的优势。
本发明的药物组合物适用于风湿性关节炎和自身免疫性疾病伴关节表现的病症。
本发明的药物组合物可以是任何常用的药物形式，可以为固体制剂，如：片剂、胶剂、栓剂、粉剂、颗粒剂、霜剂等；也可以为流体制剂，如：口服液、注射液；或膏状等。
本发明的制备方法，为本领域普通技术人员所公知的常用制备方法。
按照本发明的药物组合物，优先是将其制成片剂或胶囊，每一片剂或胶囊含有10-100mg的青蒿素或青蒿素衍生物。
附图说明：
图1为药物组合物对大鼠佐剂性关节炎的影响(右后足)
图2药物组合物对大鼠(左后足)佐剂性关节炎的影响
具体实施方式：
本发明的药物组合物一般为口服给药，也可以其他途径给药，如治疗RA和自身免疫性疾病伴关节症状的可以使用外用制剂。用量一般为1-10mg/Kg体重/天，成年患者的用量优选为每人每天20-200mg。
本发明使用的青蒿素或青蒿素衍生物(双氢青蒿素，青蒿琥酯，蒿甲醚，蒿乙醚)的制备工艺是已知的，有关其制备方法可见于诸文献报道。
通过以下试验可以对本发明进行更进一步的说明。但应该说明的是本发明的实验内容只用于说明本发明，而不是限制本发明。
本发明的药物组合物对试验性一般关节炎及免疫性关节炎的影响
实验材料
动物：①健康Wistar大白鼠，体重130±20g、180±20g和150±20g，雌雄均有。合格证编号依次为：SCXK(京)2002-0003、SCXK(京)2002-0003和SCK(京)2002-0006；②健康昆明种小白鼠，体重20±20g和13g±2g，雌雄均有。合格证编号均为SCXK(京)2002-001。均由我所动物室供给。
主要药物：
①含有青蒿提取物包括青蒿素及青蒿素衍生物(双氢青蒿素，青蒿琥酯，蒿甲醚，蒿甲醚等)的药物组合物。以下简称[药物组合物]。
②强的松(5mg/片)，东北制药总厂生产，批号20031113；
③角叉菜胶，美国Sigma公司产品，批号87F-0463；
④Freund’s完全佐剂，用卫生部北京生物制品研究所提供的卡介苗(批号20030115)制备，内含结核杆菌0.7mg/0.07ml。
仪器：鼠足容积测定仪，自制。
方法与结果
一、对大鼠角叉菜胶性足肿胀的影响
参照大鼠足趾浮肿毛细血管放大测量法，取大鼠72只，体重130±20g，雌雄各半，随机均分为五组，即空白对照组和模型组(给与给药大剂量组相当量的蒸馏水)，药物组合物大剂量组(54.0mg/Kg)、中剂量组(27.0mg/Kg)和小剂量组(5.4mg/Kg)及阳性对照组(强的松5.0mg/Kg)。均为口服灌胃给药，每日一次，连续14天。于末次给药后1小时测定鼠足容积(ml)，即将1％角叉菜胶生理盐水0.1ml注入大鼠左后肢足跖皮下致炎，分别于注入后1小时、2小时、4小时、及6及小时，用鼠足容积测定仪测定鼠足容积，计算出肿胀值，用T检验比较各时间给药组与对照组的差异情况。结果见表1。
表1.药物组合物对大鼠角叉菜胶性足肿胀的影响(X±SD)
剂量 动物数 肿胀值(ml)
组别 (mg/Kg) (只)
正常 1小时 2小时 4小时 6小时
对照组 12 29.00±1.88 30.00±1.90** 30.17±2.16** 30.17±2.17** 30.17±2.17**
模型组 12 28.33±2.49 34.25±2.86 38.67±3.63 38.67±3.63 38.67±3.63
强的松组 5 12 29.08±2.47 33.75±2.86 36.08±4.10 36.08±4.10 36.08±4.10
大剂量组 54 12 28.33±3.22 33.91±3.62 34.64±2.87** 34.64±2.87** 34.64±2.87**
中剂量组 27 12 28.00±2.34 33.42±2.47 36.58±3.06 36.58±3.06 36.58±3.06
小剂量组 5.4 12 28.67±2.54 34.58±2.35 36.33±3.53 36.33±3.53 36.33±3.53
与模型组比较：**P＜0.01
由表1可见，药物组合物给药各组足肿胀值均低于模型组，其中大剂量组作用明显，以致炎后2、4、6小时足肿胀值与模型组比较P值均小于0.01，中、小剂量组足肿胀值虽无显著差异，但与强的松作用一致。说明药物组合物能抑制致炎剂角叉菜胶所致的足肿胀，即对致炎剂角叉菜胶引起的实验性关节炎肿胀具有抑制作用，且药物作用与药物剂量有关。
二、药物组合物对大鼠肉芽肿形成的影响
取大鼠72只，体重180±20克，雌雄各半。实验前所有动物腹腔注射戊巴比妥钠30mg/kg麻醉，采用手术方法分别于每只动物背部皮下植入已消毒和称重的纽扣，缝合皮肤后，外部消毒。术后第二天，将成活动物均匀分为五组，即空白对照组(给与给药大剂量组相当量的蒸馏水)，药物组合物大剂量组(54.0mg/kg)、中剂量组(27.0mg/kg)和小剂量组(5.4mg/kg)以及阳性对照组(强的松5.0mg/kg)。各组动物均采用灌胃给药，每天给药一次，连续给药14天。于末次给药后第二天处死动物，取出植入的纽扣，仔细剥离附着组织，称重，减去纽扣重，即为肉芽肿组织重量，用T检验进行统计学处理。结果见表2。
表2药物组合物对大鼠肉芽肿形成的影响
与空白对照组比较：**P＜0.01
由表2可见，药物组合物给药各组肉芽肿重量均明显低于空白对照组
剂量 动物数 肉芽肿重量
组别 (mg/Kg) (只) (mg)
对照组 11 259.73±44.58
强的松组 5 12 173.75±43.10**
大剂量组 54 12 176.42±37.98**
中剂量组 27 12 177.17±32.25**
小剂量组 5.4 12 180.50±34.63**
(P＜0.01)。说明该药物组合物对肉芽肿的形成有明显的抑制作用，提示该药具有很好的抗结缔组织增生炎症的作用。
三、对小鼠热板法疼痛反应的影响
参照小鼠热板法加以改良，取小鼠80，体重20g±2g，雌雄各半，均分为五组，即空白对照组(给与给药大剂量组相当量的蒸馏水)，给药大剂量组(78.0mg/Kg)、中剂量组(39.0mg/Kg)和小剂量组(7.8mg/Kg)以及阳性对照组(阿斯匹林100.0mg/Kg)。均为口服灌胃给药，每天一次，连续14天。于末次给药后1小时，将各组小鼠分放在预先加热到55℃的铝盒内，以添后足作为疼痛反应的指标，记录小鼠自投入热板至出现舔后足反应的时间，用T检验进行统计学处理。结果见表3。
表3.药物组合物对小鼠热板法疼痛反映的影响( X±SD)
剂量 动物数 出现疼痛反应时间
组别 (mg/kg) (n) (s)
对照组 21 23.05±6.39
阿司匹林组 100 19 36.74±11.79**
大计量组 78 20 38.15±8.82**
中剂量组 39 19 31.68±8.39**
小计量组 7.8 21 29.29±6.63*
与对空白对照组比较：*P＜0.05，**P＜0.01
由表3可见，与空白对照组比较，药物组合物给药各组疼痛反应出现时间均延长，具有显著性差异(P＜0.05-0.01)，与阿斯匹林作用一致，其中大剂量组作用最明显，中剂量组次之，小剂量组再次之。说明药物组合物对热刺激法引起的小鼠疼痛反应有明显的抑制作用，且药物作用与药物剂量有一定的关系。
四、对小鼠化学刺激法疼痛反应的影响
按常规方法，取小鼠70只，体重13g±2g，雌雄各半，随机分为五组，即空白对照组(给与给药大剂量组相当量的蒸馏水)、给药大剂量组(78.0mg/Kg)、中剂量组(39.0mg/Kg)和小剂量组(7.8mg/Kg)以及阳性对照组(阿斯匹林100.0mg/Kg)。均为口服灌胃给药，每天一次，连续14 。于末次给药后1小时将0.6％的醋酸溶液注射于小鼠腹腔内，以引起深部的、大面积而持久的疼痛刺激，致使小鼠产生扭体反应，观察并记录各组小鼠出现扭体反应的时间(潜伏期)及20分钟内产生扭体反应的次数，用T检验进行统计学处理。结果见表4。
表4.药物组合物对小鼠化学刺激法疼痛反应的影响( X±SD)
动物数 剂量 扭体次数
组别 (n) (mg/Kg) (次数/20min)
对照组 15 38.87±8.48
阿司匹林组 12 100 23.67±10.77**
大剂量组 13 78 28.85±14.09*
中剂量组 9 39 26.89±16.68*
小剂量组 11 7.8 37.82±10.88
与空白对照组比较：*P＜0.05，**P＜0.01
注：因小鼠体重过小，在实验过程中可能由于灌胃不当而死了部分，致每组数量参差不齐。
由表4可见，与空白对照组比较，药物组合物大、中剂量组疼痛反应出现时间稍延长；20分钟内扭体次数则明显减少(P＜0.05)，与阿斯匹林作用相似。说明该药物组合物对热刺激法引起的小鼠疼痛反应有明显的抑制作用，且与药物剂量有一定的关系。
五、对大鼠佐剂性关节炎的影响
参照藤村一及WAX等法，取大鼠72只，体重150±20g，雌雄各半，随机均分为5组，其中一组为模型组(给与给药大剂量组相当量的蒸馏水)；三组为阳性对照组(强的松5.0mg/Kg)；三组为肿立消给药组，剂量分别为54.0mg/Kg、27.0mg/Kg和5.4mg/Kg。均为口服灌胃，每天一次，于注射Frdund’s完全佐剂当天开始给药，直至实验结束。将Freund’s完全佐剂0.05ml(内含死结核杆菌0.5mg)皮内注射于大鼠右后足垫内。注射佐剂前及后26天内隔日用鼠足容积测量仪测定大鼠右、左后足容积(ml)，用T检验进行统计学处理。结果见表5、表6和图1药物组合物对大鼠佐剂性关节炎的影响(右后足)和图2药物组合物对大鼠(左后足)佐剂性关节炎的影响。
表5.药物组合物对大鼠佐剂性关节炎的影响(右后足)( X±SD)
剂量 动物数 肿胀值(ml)
组别 (mg/Kg) (只)
注射前 注射后第2天 第4天 第6天 第8天 第10天
模型组 12 29.17±1.27 39.92±2.64 43.00±3.69 41.00±5.34 38.17±3.81 39.33±2.49
强的松组 5 12 28.75±1.66 39.00±3.13 39.42±2.54* 36.92±2.91* 35.66±2.94 36.25±3.59*
大剂量组 54 12 29.08±1.31 40.58±3.15 39.92±2.99* 37.83±3.61 35.67±3.82 34.42±3.78**
中剂量组 27 11 29.00±1.79 40.09±3.83 39.82±3.95 37.64±4.21 35.55±2.84 34.55±2.84**
小剂量组 5.4 12 28.67±1.56 39.25±3.08 40.00±2.34* 37.75±2.45 34.42±2.23** 34.92±2.50**
表6药物组合物对大鼠佐剂性关节炎的影响(左后足)( X±SD)
组别 剂量 动物数 肿胀值(ml)
(mg/Kg) (只) 注射前 注射后第2天 第4天 第6天 第8天 第10天
模型组 12 26.17±1.75 29.08±0.99 29.17±1.12 28.83±0.94 28.58±1.08 30.50±1.93
阳性药组 5 12 26.25±2.05 28.58±1.73 29.25±1.87 28.42±1.73 28.50±1.51 30.08±1.73
大剂量组 54 12 26.00±1.65 28.75±1.66 28.83±2.21 28.75±1.55 28.42±1.88 29.33±2.06
中剂量组 27 11 25.91±1.45 29.45±1.92 28.18±1.47 28.18±1.40 28.46±1.75 29.18±1.60
小剂量组 5.4 12 26.50±2.07 29.17±1.47 29.25±1.77 28.58±1.83 28.08.±1.97 29.50±2.78
肿胀值(ml)
第12天 第14天 第16天 第18天 第20天 第22天 第24天 第26天
29.92？.02 31.83？.99 31.42？.11 31.00？.95 30.58？.35 31.25？.18 31.42？.73 31.00？.86
29.17？.17 30.83？.21 29.58？.11* 29.83？.82 29.25？.60 29.92？.88 30.33？.78 30.33？.15
28.25？.18 29.58？.64* 28.83？.33**29.08？.64* 29.00？.45* 28.92？.35* 29.17？.25* 29.00？.49*
29.09？.43 29.82？.23* 28.82？.94**29.36？.91* 28.55？.21* 29.17？.25* 29.27？.00* 29.09？.17*
29.17？.76 30.58？.08 29.17？.43 29.58？.03 28.92？.68* 29.17？.44* 29.08？.19**29.33？.15
与模型组比较：*P＜0.05，**P＜0.01
由表可见，大鼠右后足注射Freund’s佐剂后即早期炎症反应，于注射后次日即呈明显肿胀，逐渐加重，至第4天，足肿胀达高峰，然后逐渐减轻；于注射后第10天再度肿胀，至第18天发展成十分严重的肿胀状态，持续到观察期结束；因迟发性超敏反应，未注射佐剂的左后足于第10天开始肿大，且红肿明显，持续到观察期结束。
药物组合物给药各组注射佐剂的右后足肿胀趋势与强的松组基本一致，与模型组比较P＜0.05-0.01；未注射佐剂的左后足肿胀趋势也与强的松组基本一致，与模型组比较，P值也＜0.05-0.01，且其作用的显著性还优于强的松，但药物组合物给药各组作用差异不明显。以上说明药物组合物对Freund’s佐剂所致的原发性非特异性炎症和续发性炎症损害均有明显的抑制作用，即对Frdund’s佐剂所致对大鼠佐剂性关节炎有明显的抑制作用。
上述试验结果表明：药物组合物对对致炎剂角叉菜胶所致大鼠足肿胀即实验性关节肿胀具有明显的抑制作用；对大鼠实验性肉芽肿形成即对结缔组织增生性炎症有明显的抑制作用。
同时，该药物组合物对热刺激及化学刺激所引起的小鼠疼痛反应均有明显的抑制作用。
在上述实验的基础上，我们进一步进行并完成了佐剂性关节炎实验，结果说明，药物组合物对Freund’s完全佐剂所致大鼠佐剂性关节炎(系免疫性炎症模型)有明显抑制作用。且作用与强的松一致，甚至在还某些阶段还优于强的松。
大鼠佐剂性关节炎常作为类风湿性关节炎及免疫性关节炎的一种实验模型，上述实验结果说明并肯定该药物组合物对大鼠佐剂性关节炎的防治作用，为该药物组合物防治类风湿性关节及自身免疫性疾病伴关节炎提供了一定的基础和依据。
以上部分实验资料只在于对本发明进行了说明。但应该理解的事，对于本发明的实验技术人员来说，可以在不偏离本发明的精神实质的前提下，对本发明进行的修正和改进，都属于本发明的保护范围。
下面举数个配方例对本发明作进一步详细说明。
配方例一：
用20％的青蒿素或青蒿素衍生物的药物组合物，80％中药提取物组成配方。
配方例二：
用60％的青蒿素或青蒿素衍生物的药物组合物，40％中药或天然药提取物组成配方。
配方例三：
用90％的青蒿素或青蒿素衍生物的药物组合物，10％其他合成制剂组成配方。
需要说明的是中药提取物的原材料是一般技术人员或临床上可以使用的中药或天然药。该中药或天然药的提取物可以是单品种，也可以是多品种。其他合成制剂可以是化学合成药物，也可以是药物的载体。
本发明所述的制剂是将上述药物与多种药学上可以接受的赋形剂结合，采用混合，溶解，粒化，成片，糖包衣或膜包衣等已知方法制备成固态或液态形式的制剂，如片剂，胶囊，栓剂，颗粒剂及注射剂等。
1、一种治疗类风湿性关节炎和免疫性疾病的含青蒿提取物的药物组合物，其特征在于：为含有有效剂量的青蒿提取物如青蒿素或青蒿素衍生物的药物组合物。
2、如权利要求1所述的治疗类风湿性关节炎和免疫性疾病的含青蒿提取物的药物组合物，其特征在于：所述的蒿素衍生物包括双氢青蒿素，青蒿琥酯，蒿甲醚和蒿甲醚。
3、如权利要求1所述的治疗类风湿性关节炎和免疫性疾病的含青蒿提取物的药物组合物，其特征在于：该组合物中青蒿素或青蒿素衍生物的含量为1~99％。
4、如权利要求1所述的治疗类风湿性关节炎和免疫性疾病的含青蒿提取物的药物组合物，其特征在于：所述的药物组合物含有青蒿素或青蒿素衍生物的有效剂量为20~200mg/日。
5、如权利要求1所述的治疗类风湿性关节炎和免疫性疾病的含青蒿提取物的药物组合物，其特征在于：该药物组合物可以单独使用，也可以与现有治疗RA和自身免疫性疾病的其他药物联合使用。
Medicinal compositon containing artemisine extract for treating rheumatoid arthritis and immunologic disease
A composite medicine for treating the umatoid arthritis and autoimmune disease contains the sweet worm wood herb's extract (dihydroarteannuin, artesumate, artemether, etc).
Treatment rheumatoid joint class and immune disease contain the Herba Artemisiae Annuae extract pharmaceutical composition
Technical field:
The present invention relates to a kind of medicine that is used for the treatment of rheumatoid joint class and autoimmune disease companion arthritic symptom, contain arteannuin or artemisinin derivative (dihydroarteannuin especially for treatment rheumatoid arthritis and autoimmune disease companion arthritic symptom, artesunate, Artemether, Artemether etc.) pharmaceutical composition.
Background technology:
Rheumatoid arthritis (hereinafter to be referred as RA) is a kind of of autoimmune disease, it is a kind of worldwide agnogenic systemic autoimmune disease, its sickness rate 0.4～1%, its principal character is with chronic, symmetry and tip joint diffusivity synovitis, the carrying out property destruction of joint of various degree appears latter stage, degeneration and function of joint are lost, and seriously affect patient's work and viability, cause huge burden to society.And other autoimmune disease is also usually with similar joint symptom, such treatment of diseases still there is not specific medicament, non-steroid class analgesic agents and the immunosuppressant treatments of adopting more, disease controlling fully not only, and have bigger poison to pay effect.
Research is subjected to domestic and international expert and patient's attention to Chinese medicine to rheumatoid arthritis and autoimmune disease in recent years, has developed the medicine of some treatment RA, and for example: Chinese patent application 02137816 discloses the medicine compositions of a kind of RA, wherein contain Chinese medicinal ingredients: Poria 12%, Radix Angelicae Sinensis 12%, the Fructus Kochiae 12%, Cortex Acanthopancis 10%, Folium Eriobotryae 10%, Cortex erythrinae 9%, Radix Cynanchi Atrati 9%, Radix Scutellariae 8%, Rhizoma Coptidis 7%, Herba Pogostemonis 6%, Caulis Akebiae 5%.Chinese patent application 01117709 discloses a kind of medicine for the treatment of rheumatoid arthritis for another example, it is with Radix Polygoni Multiflori, Radix Codonopsis, Radix Angelicae Sinensis, the Radix Astragali, Rhizoma Polygonati, the Rhizoma Atractylodis Macrocephalae, Rhizoma Cibotii, Scorpio, Zaocys, Pheretima, Formica fusca, Radix Salviae Miltiorrhizae, Ramulus Mori, Ramulus Cinnamomi, Rhizoma Atractylodis, Rhizoma Et Radix Notopterygii, Radix Angelicae Pubescentis, Radix Saposhnikoviae, Radix Gentianae Macrophyllae, Herba Taxilli, the Cortex Eucommiae, Radix Cyathulae, Cortex Phellodendri, Rhizoma Homalomenae, bore Cortex Illici difengpi, Olibanum, Myrrha, Caulis Sinomenii, Rhizoma Arisaematis, Caulis Spatholobi, Fructus Mori, Rhizoma Corydalis, Rhizoma Chuanxiong, Semen Ziziphi Spinosae, the Rhizoma Anemarrhenae, Poria, Radix Aconiti Kusnezoffii, Radix Aconiti, Herba Epimedii, Flos Carthami, Radix Dipsaci, Cortex Moutan, Caulis Lonicerae, Radix Paeoniae Rubra, Semen Coicis, Cortex erythrinae, Caulis Trachelospermi, Radix Glycyrrhizae is a raw material, different qualities according to every flavor Chinese medicine, at the different symptoms of rheumatoid arthritis, be mixed with basic medicament in proportion, even the medicament that cold hot very person adapts.
Above-mentioned these Chinese medicine compositions generally all are the routine administrations of Chinese medicine, use Shi doctor also must carry out prescription according to patient's situation according to the principle of differentiation of tcm; Also have some Chinese patent medicine compositions more, preparation is complicated, and practical application can't be satisfied clinician and patient's needs fully.
Arteannuin is Chinese scholar independent development and by internationally recognized Chinese medicine extract, arteannuin and derivant thereof are effective antimalarial of a class and antimalarial agent compositions.The effective monomer component that system extracts from China Chinese medicine Herba Artemisiae annuae has been the malaria new drug by world health organisation recommendations.Along with country and each research unit are goed deep into the continuation of arteannuin research, having developed some is the anti-malarial agents of the new compound preparation of main component with the arteannuin in recent years, as: Chinese patent application 00113134 discloses a kind of compound preparation for the treatment of malaria; Also constantly found the application in other frontiers simultaneously, as: Chinese patent application 99103346 discloses a kind of pharmaceutical composition that contains dihydroarteannuin for the treatment of lupus erythematosus and photosensitive diseases etc.Existing bibliographical information can be applied to the Herba Artemisiae Annuae oil liniment treatment of tinea, by research to the external antifungic action of arteannuin, the antibiotic universal effect that confirms arteannuin is similar to broad-spectrum antifungal medicine ketoconazole commonly used at present, and the effect to some fungus is better than ketoconazole, and promptly its antifungic action is respond well.
Summary of the invention:
Purpose of the present invention, provide a kind of treat rheumatoid joint class and immune disease safely and effectively contain the Herba Artemisiae Annuae extract pharmaceutical composition.
Technical scheme of the present invention is as follows.
A kind of treat rheumatoid arthritis and immune disease contain the Herba Artemisiae Annuae extract pharmaceutical composition, be the arteannuin that contains effective dose or the pharmaceutical composition of artemisinin derivative.
Described artemisin derivant comprises dihydroarteannuin, artesunate, Artemether and Artemether.
The content of arteannuin or artemisinin derivative is 1～99% in the said composition.
The effective dose that described pharmaceutical composition contains arteannuin or artemisinin derivative is 20～200mg/ day.
This pharmaceutical composition can use separately, also can unite use with the other drug of existing treatment RA and autoimmune disease.
Described pharmaceutical composition is can be any medicament forms commonly used, as: solid preparation, fluid, or paste etc.
The present invention is based on that such fact finishes.This case inventor finds that in secular clinical treatment RA and autoimmune disease and various arthritic process the Chinese medicine Herba Artemisiae Annuae has heat-clearing and toxic substances removing preferably, detumescence, pain relieving effect.And arteannuin is Chinese medicine one kind new medicine that China began one's study from the seventies, we are studying arteannuin or derivatives thereof and the pharmaceutical composition that contains arteannuin aspect immunity and the autoimmune disease for this reason, show that arteannuin has on the immunoregulatory basis, prove all that from pharmacodynamics and clinical research arteannuin or artemisinin derivative to the curative effect preferably that has of RA and autoimmune disease companion joint symptom, have antiinflammatory, analgesia, immunoregulatory curative effect.And has instant effect, the advantage of no obvious toxic and side effects.
Pharmaceutical composition of the present invention is applicable to the disease of rheumatic arthritis and autoimmune disease companion joint performance.
Pharmaceutical composition of the present invention can be any medicament forms commonly used, can be solid preparation, as: tablet, colloid, suppository, powder, granule, cream etc.; Also can be fluid preparation, as: oral liquid, injection; Or paste etc.
Preparation method of the present invention is the known preparation method commonly used of those of ordinary skills.
According to pharmaceutical composition of the present invention, preferentially be to be made into tablet or capsule, each tablet or capsule contain arteannuin or the artemisinin derivative of 10-100mg.
Description of drawings:
Fig. 1 is the influence (right back foot) of pharmaceutical composition to rat assist agent arthritis
Fig. 2 pharmaceutical composition is to the influence of rat (left back foot) adjuvant-induced arthritis
The specific embodiment:
Pharmaceutical composition of the present invention is generally oral administration, also can other administration, can use external preparation as treatment RA and autoimmune disease companion joint symptom.Consumption is generally the 1-10mg/Kg body weight/day, and the consumption of adult patients is preferably 20-200mg for each person every day.
The arteannuin that the present invention uses or the preparation technology of artemisinin derivative (dihydroarteannuin, artesunate, Artemether, arteether) are known, and relevant its preparation method is found in all bibliographical informations.
Can further illustrate the present invention by following test.But should be noted that experiment content of the present invention only is used to illustrate the present invention, rather than restriction the present invention.
Pharmaceutical composition of the present invention is to the influence of tentative general arthritis and autoimmune arthritis
Experiment material
Animal: 1. healthy Wistar rat, body weight 130 ± 20g, 180 ± 20g and 150 ± 20g, male and female all have.Quality certification numbering is followed successively by: SCXK (capital) 2002-0003, SCXK (capital) 2002-0003 and SCK (capital) 2002-0006; 2. healthy Kunming kind white mice, body weight 20 ± 20g and 13g ± 2g, male and female all have.Quality certification numbering is SCXK (capital) 2002-001.Supply with by my animal housing of institute.
Main medicine:
1. contain the pharmaceutical composition that Herba Artemisiae Annuae extract comprises arteannuin and artemisinin derivative (dihydroarteannuin, artesunate, Artemether, Artemether etc.).Hereinafter to be referred as [pharmaceutical composition].
2. prednisone (5mg/ sheet), Dongbei Pharmaceutical General Factory production, lot number 20031113;
3. carrageenin, U.S. Sigma company product, lot number 87F-0463;
4. Freund ' s Freund's complete adjuvant, bacillus calmette-guerin vaccine (lot number 20030115) preparation with the Beijing Biological Product Inst., Ministry of Public Health provides includes tubercule bacillus 0.7mg/0.07ml.
Instrument: Mus foot volume determination instrument, self-control.
Method and result
One, to the influence of rat carrageenan foot swelling
With reference to rat toes edema blood capillary measurement by magnification method, get 72 of rats, body weight 130 ± 20g, male and female half and half, be divided into five groups at random, be blank group and model group (giving distilled water) with the heavy dose of group of administration a great deal of, the heavy dose of group of pharmaceutical composition (54.0mg/Kg), middle dosage group (27.0mg/Kg) and small dose group (5.4mg/Kg) and positive controls (prednisone 5.0mg/Kg).Be the oral administration gavage administration, once a day, continuous 14 days.1 hour mensuration Mus foot volume (ml) after the last administration, be about to 1% carrageenin normal saline 0.1ml and inject the subcutaneous inflammation that causes of the rat left hind foot sole of the foot, respectively at inject back 1 hour, 2 hours, 4 hours, and 6 and hour, measure Mus foot volume with Mus foot volume determination instrument, calculate the swelling value, compare the difference condition of each time administration group and matched group with the T check.The results are shown in Table 1.
Table 1. pharmaceutical composition is to the influence of rat carrageenan foot swelling (X ± SD)
Dosage number of animals swelling value (ml)
Group (mg/Kg) (only)
Model group 12 28.33 ± 2.49 34.25 ± 2.86 38.67 ± 3.63 38.67 ± 3.63 38.67 ± 3.63
Prednisone group 5 12 29.08 ± 2.47 33.75 ± 2.86 36.08 ± 4.10 36.08 ± 4.10 36.08 ± 4.10
Heavy dose of group 54 12 28.33 ± 3.22 33.91 ± 3.62 34.64 ± 2.87 *34.64 ± 2.87 *34.64 ± 2.87 *
Middle dosage group 27 12 28.00 ± 2.34 33.42 ± 2.47 36.58 ± 3.06 36.58 ± 3.06 36.58 ± 3.06
Small dose group 5.4 12 28.67 ± 2.54 34.58 ± 2.35 36.33 ± 3.53 36.33 ± 3.53 36.33 ± 3.53
Compare with model group: *P＜0.01
By table 1 as seen, the pharmaceutical composition administration is respectively organized the foot swelling value and all is lower than model group, and wherein heavy dose of group of effect is obvious, thus 2,4, the 6 hours foot swelling values in scorching back and model group relatively the P value all less than 0.01, in, though small dose group foot swelling value do not have significant difference, and is consistent with the prednisone effect.Illustrate that pharmaceutical composition can suppress the foot swelling due to the proinflammatory agent carrageenin, promptly inhibited to the experimental arthritis swelling that the proinflammatory agent carrageenin causes, and drug effect is relevant with drug dose.
Two, pharmaceutical composition is to the influence of rat granuloma formation
Get 72 of rats, body weight 180 ± 20 grams, male and female half and half.All animal lumbar injection pentobarbital sodium 30mg/kg anesthesia before the experiment, the button that adopts operation method to sterilize and weighed respectively at every subcutaneous implantation of back part of animal, behind the skin suture, outside sterilization.Second day after operation, to become live animal evenly to be divided into five groups, be blank group (giving distilled water) with the heavy dose of group of administration a great deal of, the heavy dose of group of pharmaceutical composition (54.0mg/kg), middle dosage group (27.0mg/kg) and small dose group (5.4mg/kg) and positive controls (prednisone 5.0mg/kg).Each treated animal all adopts gastric infusion, and be administered once every day, successive administration 14 days.Put to death animal in second day after the last administration, take out the button of implanting, carefully peel off adhering tissue, weigh, it is heavy to deduct button, is granuloma tissue weight, carries out statistical procedures with the T check.The results are shown in Table 2.
The influence that table 2 pharmaceutical composition forms the rat granuloma
Compare with the blank group: *P＜0.01
By table 2 as seen, the pharmaceutical composition administration is respectively organized granuloma weight and all is starkly lower than the blank group
Dosage number of animals granuloma weight
Group (mg/Kg) (only) (mg)
Matched group 11 259.73 ± 44.58
Prednisone group 5 12 173.75 ± 43.10**
Heavy dose of group 54 12 176.42 ± 37.98**
Middle dosage group 27 12 177.17 ± 32.25**
Small dose group 5.4 12 180.50 ± 34.63**
(P＜0.01)。Illustrate that this pharmaceutical composition is formed with the obvious suppression effect to granulomatous, points out this medical instrument to have good resistive connection to form the effect of hamartoplasia inflammation.
Three, to the influence of mice hot plate method pain reaction
Improved with reference to the mice hot plate method, get mice 80, body weight 20g ± 2g, male and female half and half, be divided into five groups, be blank group (giving distilled water) with the heavy dose of group of administration a great deal of, the heavy dose of group of administration (78.0mg/Kg), middle dosage group (39.0mg/Kg) and small dose group (7.8mg/Kg) and positive controls (aspirin 100.0mg/Kg).Be the oral administration gavage administration, once a day, continuous 14 days.After the last administration 1 hour, each group mice divided be placed in the aluminum box that is heated to 55 ℃ in advance, to add the index of metapedes as pain reaction, the record mice carries out statistical procedures from dropping into hot plate to the time that the metapedes reaction occurs licking with the T check.The results are shown in Table 3.
The influence that table 3. pharmaceutical composition reflects mice hot plate method pain (X ± SD)
The pain reaction time appears in the dosage number of animals
Group (mg/kg) is (s) (n)
Matched group 21 23.05 ± 6.39
Aspirin group 100 19 36.74 ± 11.79 *
Big metering organizes 78 20 38.15 ± 8.82 *
Middle dosage group 39 19 31.68 ± 8.39 *
Subtotal amount group 7.8 21 29.29 ± 6.63 *
With to the blank group relatively: *P＜0.05, *P＜0.01
By table 3 as seen, compare with the blank group, the pharmaceutical composition administration is respectively organized the pain reaction time of occurrence and is all prolonged, (P＜0.05-0.01), consistent with the aspirin effect, wherein heavy dose of group of effect is the most obvious to have significant difference, middle dosage group is taken second place, and small dose group is taken second place again.Illustrate that pharmaceutical composition has the obvious suppression effect to the mice pain reaction that the thermostimulation method causes, and drug effect and drug dose there is certain relation.
Four, to the influence of mice chemical stimulation method pain reaction
According to a conventional method, get 70 of mices, body weight 13g ± 2g, male and female half and half, be divided into five groups at random, i.e. blank group (giving distilled water), the heavy dose of group of administration (78.0mg/Kg), middle dosage group (39.0mg/Kg) and small dose group (7.8mg/Kg) and positive controls (aspirin 100.0mg/Kg) with the heavy dose of group of administration a great deal of.Be the oral administration gavage administration, once a day, continuous 14.After the last administration, 0.6% acetum was injected in the mouse peritoneal in 1 hour, with cause the deep, large tracts of land and persistent pain stimulation, cause mice to produce writhing response, observe and the number of times that produces writhing response in the time (incubation period) and 20 minutes that writhing response appears in mice respectively organized in record, carry out statistical procedures with the T check.The results are shown in Table 4.
Table 4. pharmaceutical composition is to the influence of mice chemical stimulation method pain reaction (X ± SD)
Number of animals dosage is turned round the body number of times
Group (n) is (number of times/20min) (mg/Kg)
Matched group 15 38.87 ± 8.48
Heavy dose of group 13 78 28.85 ± 14.09 *
Middle dosage group 9 39 26.89 ± 16.68 *
Small dose group 11 7.8 37.82 ± 10.88
Compare with the blank group: *P＜0.05, *P＜0.01
Annotate: because of the mice body weight too small, may be in experimentation owing to irritate the improper and part in the dust of stomach, it is uneven to cause every group of quantity.
By table 4 as seen, compare with the blank group, the big or middle dosage group of pharmaceutical composition pain reaction time of occurrence prolongs slightly; Turn round the body number of times in 20 minutes and then obviously reduce (P＜0.05), similar to the aspirin effect.Illustrate that this pharmaceutical composition has the obvious suppression effect to the mice pain reaction that the thermostimulation method causes, and certain relation is arranged with drug dose.
Five, to the influence of rat assist agent arthritis
With reference to methods such as rattan village one and WAX, get 72 of rats, body weight 150 ± 20g, male and female half and half are divided into 5 groups at random, and wherein one group is model group (giving the distilled water with the heavy dose of group of administration a great deal of); Three groups of positive matched groups (prednisone 5.0mg/Kg); Three groups are the swollen upright administration group that disappears, and dosage is respectively 54.0mg/Kg, 27.0mg/Kg and 5.4mg/Kg.Be oral administration gavage, once a day, began administration the same day, finish until experiment in injection Frdund ' s Freund's complete adjuvant.With Freund ' s Freund's complete adjuvant 0.05ml (include fast knot nuclear bacillus 0.5mg) intradermal injection in the right back foot pad of rat.Injection adjuvant is measured the rat right side, left back sufficient volume (ml) with Mus foot volumetric measurement instrument before and after in 26 days the next day, carries out statistical procedures with the T check.The results are shown in Table 5, table 6 and Fig. 1 pharmaceutical composition be to the influence to rat (left back foot) adjuvant-induced arthritis of the influence (right back foot) of rat assist agent arthritis and Fig. 2 pharmaceutical composition.
Table 5. pharmaceutical composition is to the influence (right back foot) of rat assist agent arthritis (X ± SD)
Dosage number of animals swelling value (ml)
Group (mg/Kg) (only)
The injection back is the 2nd day the 4th day the 6th day the 8th day the 10th day before the injection
Model group 12 29.17 ± 1.27 39.92 ± 2.64 43.00 ± 3.69 41.00 ± 5.34 38.17 ± 3.81 39.33 ± 2.49
Prednisone group 5 12 28.75 ± 1.66 39.00 ± 3.13 39.42 ± 2.54 *36.92 ± 2.91 *35.66 ± 2.94 36.25 ± 3.59 *
Heavy dose of group 54 12 29.08 ± 1.31 40.58 ± 3.15 39.92 ± 2.99 *37.83 ± 3.61 35.67 ± 3.82 34.42 ± 3.78 *
Middle dosage group 27 11 29.00 ± 1.79 40.09 ± 3.83 39.82 ± 3.95 37.64 ± 4.21 35.55 ± 2.84 34.55 ± 2.84 *
Small dose group 5.4 12 28.67 ± 1.56 39.25 ± 3.08 40.00 ± 2.34 *37.75 ± 2.45 34.42 ± 2.23 *34.92 ± 2.50 *
Table 6 pharmaceutical composition is to the influence (left back foot) of rat assist agent arthritis (X ± SD)
Group dosage number of animals swelling value (ml)
(mg/Kg) injected the back the 2nd day the 4th day the 6th day the 8th day the 10th day before (only) injection
Model group 12 26.17 ± 1.75 29.08 ± 0.99 29.17 ± 1.12 28.83 ± 0.94 28.58 ± 1.08 30.50 ± 1.93
Positive drug group 5 12 26.25 ± 2.05 28.58 ± 1.73 29.25 ± 1.87 28.42 ± 1.73 28.50 ± 1.51 30.08 ± 1.73
Heavy dose of group 54 12 26.00 ± 1.65 28.75 ± 1.66 28.83 ± 2.21 28.75 ± 1.55 28.42 ± 1.88 29.33 ± 2.06
Middle dosage group 27 11 25.91 ± 1.45 29.45 ± 1.92 28.18 ± 1.47 28.18 ± 1.40 28.46 ± 1.75 29.18 ± 1.60
Small dose group 5.4 12 26.50 ± 2.07 29.17 ± 1.47 29.25 ± 1.77 28.58 ± 1.83 28.08. ± 1.97 29.50 ± 2.78
Swelling value (ml)
The 12nd day the 14th day the 16th day the 18th day the 20th day the 22nd day the 24th day the 26th day
29.92？.02 31.83？.99 31.42？.11 31.00？.95 30.58？.35 31.25？.18 31.42？.73 31.00？.86
29.17？.17 30.83？.21 29.58？.11 *?29.83？.82 29.25？.60 29.92？.88 30.33？.78 30.33？.15
28.25？.18 29.58？.64 *?28.83？.33 **29.08？.64 *?29.00？.45 *?28.92？.35 *?29.17？.25 *?29.00？.49 *
29.09？.43 29.82？.23 *?28.82？.94 **29.36？.91 *?28.55？.21 *?29.17？.25 *?29.27？.00 *?29.09？.17 *
29.17？.76 30.58？.08 29.17？.43 29.58？.03 28.92？.68 *?29.17？.44 *?29.08？.19 **29.33？.15
Compare with model group: *P＜0.05, *P＜0.01
By table as seen, be early stage inflammatory reaction behind the right back foot injection of rat Freund ' the s adjuvant, promptly be obvious swelling next day in the injection back, increase the weight of gradually, to the 4th day, foot swelling reached the peak, alleviates gradually then; In injection back swelling once again in the 10th day, developed into very serious swelling state to the 18th day, last till that the observation period finishes; Because of delayed hypersensitivity, the left back foot of injection adjuvant did not begin enlargement in the 10th day, and obviously red and swollen, lasted till that the observation period finishes.
The right back foot swelling trend and the prednisone group basically identical of injection adjuvant respectively organized in the pharmaceutical composition administration, compares P＜0.05-0.01 with model group; Not the left back foot swelling trend of injection adjuvant also with prednisone group basically identical, with model group relatively, the P value also＜0.05-0.01, and the significance of its effect also is better than prednisone, but that difference between the effects is respectively organized in the pharmaceutical composition administration is not obvious.More than the explanation pharmaceutical composition all has the obvious suppression effect to constitutional nonspecific inflammation and the infringement of supervention inflammation due to Freund ' the s adjuvant, promptly due to Frdund ' s adjuvant rat assist agent arthritis is had the obvious suppression effect.
Above-mentioned result of the test shows: pharmaceutical composition is that experimental arthroncus has the obvious suppression effect to rat paw edema due to the proinflammatory agent carrageenin; Formation promptly has the obvious suppression effect to the connective tissue proliferation inflammation to the rat experiment granuloma.
Simultaneously, this pharmaceutical composition all has the obvious suppression effect to thermostimulation and the caused mice pain reaction of chemical stimulation.
On the basis of above-mentioned experiment, we further carry out and have finished the adjuvant-induced arthritis experiment, presentation of results, and pharmaceutical composition has obvious inhibitory action to rat assist agent arthritis (being the immune inflammation model) due to Freund ' the s Freund's complete adjuvant.And effect is consistent with prednisone, even also is better than prednisone in some stage of going back.
A kind of experimental model of rat assist agent arthritis Chang Zuowei rheumatoid arthritis and autoimmune arthritis, the explanation of above-mentioned experimental result also certainly this pharmaceutical composition to the preventive and therapeutic effect of rat assist agent arthritis, for this pharmaceutical composition control rheumatoid joint and autoimmune disease companion arthritis provide certain basis and foundation.
Only be to describe the present invention with the top experimental data.But the thing that should be appreciated that, for experimental technique personnel of the present invention, can be under the prerequisite that does not depart from spirit of the present invention, correction and improvement to the present invention carries out all belong to protection scope of the present invention.
Lifting several Formulation Examples below is described in further detail the present invention.
Formulation Example one:
The arteannuin with 20% or the pharmaceutical composition of artemisinin derivative, 80% Chinese medicine extract compositing formula.
Formulation Example two:
The arteannuin with 60% or the pharmaceutical composition of artemisinin derivative, 40% Chinese medicine or crude drug extract compositing formula.
Formulation Example three:
The arteannuin with 90% or the pharmaceutical composition of artemisinin derivative, 10% other synthesising preparation compositing formulas.
The raw material that need to prove Chinese medicine extract is those skilled in the art or operable clinically Chinese medicine or crude drug.The extract of this Chinese medicine or crude drug can be a single variety, also can be many kinds.Other synthesising preparations can be chemical synthetic drugs, also can be the carriers of medicine.
Preparation of the present invention is that said medicine is combined with multiple pharmaceutically acceptable excipient, adopts and mixes, dissolving, granulation; in flakes, known methods such as sweet tablet or film coating are prepared into the preparation of solid-state or liquid form, as tablet; capsule, suppository, granule and injection etc.
1, a kind of pharmaceutical composition that contains Herba Artemisiae Annuae extract for the treatment of rheumatoid arthritis and immune disease is characterized in that: be the Herba Artemisiae Annuae extract that contains effective dose such as the pharmaceutical composition of arteannuin or artemisinin derivative.
2, the pharmaceutical composition that contains Herba Artemisiae Annuae extract of treatment rheumatoid arthritis as claimed in claim 1 and immune disease is characterized in that: described artemisin derivant comprises dihydroarteannuin, artesunate, Artemether and Artemether.
3, the pharmaceutical composition that contains Herba Artemisiae Annuae extract of treatment rheumatoid arthritis as claimed in claim 1 and immune disease is characterized in that: the content of arteannuin or artemisinin derivative is 1 ~ 99% in the said composition.
4, the pharmaceutical composition that contains Herba Artemisiae Annuae extract of treatment rheumatoid arthritis as claimed in claim 1 and immune disease is characterized in that: the effective dose that described pharmaceutical composition contains arteannuin or artemisinin derivative is 20 ~ 200mg/ day.
5, the pharmaceutical composition that contains Herba Artemisiae Annuae extract of treatment rheumatoid arthritis as claimed in claim 1 and immune disease, it is characterized in that: this pharmaceutical composition can use separately, also can unite use with the other drug of existing treatment RA and autoimmune disease.
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