WO2017101536A1 - 一种防治关节炎的药物组合物及其制备方法 - Google Patents

一种防治关节炎的药物组合物及其制备方法 Download PDF

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WO2017101536A1
WO2017101536A1 PCT/CN2016/099076 CN2016099076W WO2017101536A1 WO 2017101536 A1 WO2017101536 A1 WO 2017101536A1 CN 2016099076 W CN2016099076 W CN 2016099076W WO 2017101536 A1 WO2017101536 A1 WO 2017101536A1
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pharmaceutical composition
preparation
zinc
inorganic compound
containing inorganic
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PCT/CN2016/099076
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English (en)
French (fr)
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米军
刘紫鹃
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米军
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Priority to US15/544,641 priority Critical patent/US10485826B2/en
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Priority to US16/694,408 priority patent/US20200085863A1/en

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    • A—HUMAN NECESSITIES
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    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
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Definitions

  • the invention relates to a pharmaceutical composition for preventing and treating arthritis and a preparation method thereof, and belongs to the field of medicine.
  • Arthritis refers to inflammatory diseases that occur in human joints and surrounding tissues, and can be divided into dozens.
  • the most common type of osteoarthritis is a degenerative joint disease, in addition to various types such as rheumatoid arthritis, rheumatoid arthritis, and gouty arthritis.
  • the etiology of these diseases is not completely clear, and the clinical manifestations are similar.
  • the main symptoms are red, swelling, heat, pain, dysfunction and joint deformity of the joints.
  • Common anti-inflammatory drugs are mainly non-steroidal anti-inflammatory drugs, including cloth. Lofene, aspirin, diclofenac, etc., of which the dipyridic acid diethylamine as the main active ingredient of the Futalin ointment is widely used.
  • the stimulating effect on the gastrointestinal mucosa greatly limits the clinical application of these drugs, so it is urgent to develop alternative drugs with significant curative effects and few side effects.
  • Selenium and zinc are indispensable trace elements in human and animal organisms and play an important role in physiological activities. In some parts of China, selenium deficiency causes endemic diseases. For example, the lack of selenium in the diet of the Qinghai-Tibet Plateau is a higher risk for Kashin-Beck disease.
  • a typical representative of selenium-containing inorganic substances is sodium selenite.
  • CN 1511541A, CN 1679622A also discloses the use of tablets, granules, capsules and oral liquids prepared by using sodium selenite as an active ingredient in the preparation of a medicament for treating osteoarthritis and rheumatoid arthritis.
  • zinc-containing inorganic substances which are commonly used in clinical practice, are represented by zinc chloride, and are often prepared as ointments for the treatment of acute or subacute dermatitis, eczema, lice and mild, small-area skin ulcers.
  • the object of the present invention is to provide a pharmaceutical composition for preventing and treating arthritis, which solves the problems of poor efficacy of existing drugs, oral administration of drugs, and stimulation of gastrointestinal mucosa to produce adverse reactions.
  • the present invention provides a pharmaceutical composition for preventing and treating arthritis, which is a preparation prepared from the following raw materials: a selenium-containing inorganic compound, and a zinc-containing inorganic compound.
  • it is a preparation prepared from the following weight ratio raw materials: 3 parts of a zinc-containing inorganic compound and 3 parts of a selenium-containing inorganic compound.
  • the zinc-containing inorganic compound is one or more selected from the group consisting of zinc sulfate, zinc chloride or zinc acetate; and the selenium-containing inorganic compound is sodium selenite.
  • the preparation is prepared from each weight-weighted drug substance, together with a pharmaceutically acceptable adjuvant or auxiliary ingredient.
  • the preparation is an external preparation.
  • the preparation is selected from the group consisting of a gel, a cream, an ointment or a patch.
  • the invention provides a preparation method of the pharmaceutical composition, which comprises the steps of: weighing each weight ratio raw material medicine, adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients, that is, obtaining.
  • the invention also provides the use of the pharmaceutical composition for the manufacture of a medicament for the treatment and/or prevention of arthritis.
  • the medicament is for treating and/or preventing osteoarthritis, rheumatoid arthritis, rheumatoid arthritis, gouty arthritis, reactive arthritis, infectious arthritis, traumatic arthritis, carpal tunnel synthesis A drug that causes one or several diseases in bursitis.
  • the medicament is a medicament for treating and/or preventing osteoarthritis.
  • the present invention provides a pharmaceutical composition for preventing and treating arthritis.
  • the pharmaceutical composition can be prepared as an external preparation, providing a faster and safer treatment for various joint pains.
  • selenium salts have a certain therapeutic effect on joint inflammation, inorganic selenium salts are difficult to transport into inflammatory cells for external use, and the pharmaceutical composition of the present invention skillfully solves this problem.
  • the pharmacodynamic experiment proves that the pharmaceutical composition of the invention can significantly reduce the level of inflammatory cytokines in the joint lavage fluid of the arthritis model, and the ointment can even achieve the curative effect superior to the futalin ointment, and has good clinical application prospect.
  • the raw materials and equipment used in the specific embodiments of the present invention are known products and are obtained by purchasing commercially available products.
  • Formulation 0.10 g of zinc sulfate, 0.10 g of sodium selenite, 940 10 g of carbomer, 75 g of glycerin, 80 2 g of polysorbate, 13.5 g of triethanolamine, and distilled water to 1000 g.
  • Formulation 0.5 g of zinc sulfate, 0.1 g of sodium selenite, 10 g of carbomer 940, 75 g of glycerin, 80 g of polysorbate, 13.5 g of triethanolamine, and distilled water to 1000 g.
  • zinc sulfate 0.3g zinc sulfate 0.3g, sodium selenite 0.3g, gelatin 60g, cellulose sodium 100g, sodium polyacrylate 30g, kaolin 120g, PEG400 (polyethylene glycol 400) 80g, carbomer 100g, Yamanashi 20 g of alcohol, 200 g of glycerin, and 290 g of water.
  • Formulation 0.5 g of zinc chloride, 0.1 g of sodium selenite, 10 g of carbomer 940, 75 g of glycerin, 80 g of polysorbate, 13.5 g of triethanolamine, and distilled water to 1000 g.
  • Formulation 0.3 g of zinc acetate, 0.3 g of sodium selenite, 940 5 g of carbomer, 75 g of glycerin, 80 2 g of polysorbate, 13.5 g of triethanolamine, and distilled water to 1000 g.
  • zinc chloride 0.1g sodium selenite 0.5g, white petrolatum 100g, stearyl alcohol 100g, liquid paraffin 50g, glyceryl monostearate 60g, OP emulsifier 10g, flat plus O 20g, glycerin 50g, laurel Azoxystrobin 20g.
  • Formulation 0.5 g of zinc sulfate, 940 10 g of carbomer, 75 g of glycerin, 80 2 g of polysorbate, 13.5 g of triethanolamine, and distilled water to 1000 g.
  • cytokines and chemokines such as TNF- ⁇ (tumor necrosis factor- ⁇ ), NF-kB (transcription factor protein family) or IL (interleukin) and the like.
  • EXPERIMENTAL OBJECTIVE To investigate the effects of the pharmaceutical composition of the present invention on the levels of cytokines (TNF- ⁇ and IL-1 ⁇ ) in a rabbit knee osteoarthritis model.
  • Animal grouping 130 New Zealand white rabbits were randomly divided into 13 groups: blank group, model group, control group, ZN group, SE group, treatment group 1-8 groups, 10 rats in each group, weighing markers.
  • Modeling method Except for the blank group, the other 12 groups were fixed with the plaster in the straight position by the Vandman method. The fixation ranged from 3cm under the ankle joint of the rabbit to 1.5cm below the inguinal region, and the dorsiflexion was 30-40°, and the fixation time was 6 weeks. After 6 weeks of fixation, each group of animals was randomly sacrificed one by one, and articular cartilage was taken for pathological examination to observe the modeling. After successful modeling, remove the fixation and shave.
  • the control group was coated with Futalin ointment and the thickness was about 2 mm, and the surface of the joint was uniformly covered twice a day.
  • the treatment group was separately applied with the preparations prepared according to Examples 1 to 8, and the thickness was about 2 mm, and the surface of the stent was uniformly covered twice a day.
  • the ZN group was externally applied with the gel preparation prepared according to Comparative Example 1, and the SE group was externally coated with the gel preparation prepared according to Comparative Example 2, having a thickness of about 2 mm, and uniformly covering the surface of the molded joint twice a day.
  • the model group was externally coated with Vaseline, with a thickness of about 2 mm, and evenly covered the model joints twice a day.
  • the blank group also applied Vaseline to the surface of the right knee joint, with a thickness of about 2 mm, twice a day.
  • the experimental data were expressed as mean ⁇ standard deviation (x ⁇ s), and t or t' test was used to compare the two groups.
  • the test level ⁇ 0.05, and the analysis was performed using SPSS 17.0 software.
  • TNF- ⁇ and IL-1 ⁇ in the joints of the blank group were lower than that of the model group, and there was a significant difference (P ⁇ 0.01), indicating that the inflammatory cytokines in the left knee joint fluid increased after modeling.
  • the content of TNF- ⁇ and IL-1 ⁇ in the joint lavage fluid of the control group and the treatment group was lower than that of the model control group, and there was a significant difference (P ⁇ 0.01), indicating that the pharmaceutical composition of the present invention can significantly reduce the joint irrigating solution of the arthritis model.

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Abstract

一种防治关节炎的药物组合物，它是由下述原料药制备而成的制剂：含硒无机化合物、含锌无机化合物。所述的药物组合物可制备成外用制剂。

Description

一种防治关节炎的药物组合物及其制备方法 技术领域
本发明涉及一种防治关节炎的药物组合物及其制备方法，属于医药领域。
背景技术
关节炎泛指发生在人体关节及其周围组织的炎性疾病，可分为数十种。其中最常见的骨关节炎是一种退行性关节病变，另外还有诸如风湿性关节炎、类风湿关节炎、痛风性关节炎等多种类型。这类疾病的病因尚不完全明确，临床表现近似，以关节的红、肿、热、痛、功能障碍及关节畸形为主要症状，常用的抗炎药物主要为非甾体抗炎药，包括布洛芬、阿司匹林、双氯芬酸等，其中以双氯酚酸二乙胺为主要活性成份的扶他林软膏应用较为广泛。然而，对胃肠道粘膜的刺激作用大大限制了这类药物在临床上的应用，因此亟需开发出疗效显著、副作用小的替代药物。
硒和锌都是人和动物机体不可缺少的微量元素，在生理活动中发挥着重要作用。在中国的某些地方，硒缺乏导致地方病的发生。例如青藏高原人群的饮食中缺乏硒，这些人更患大骨节病的风险很高。含硒无机物的典型代表为亚硒酸钠，国内外已有多家制药企业生产亚硒酸钠的片剂，用以治疗和预防属于地方病的克山病和大骨节病；CN 1511541A、CN 1679622A还公开了以亚硒酸钠为活性成份制备的片剂、颗粒剂、胶囊剂和口服液在制备治疗骨性关节炎、类风湿性关节炎的药物中的用途。另外，目前临床上使用较为普遍的含锌无机物以氯化锌为代表，常制备成软膏剂，用于治疗急性或亚急性皮炎、湿疹、痱子及轻度、小面积的皮肤溃疡。
然而，迄今尚未见将含硒无机物、含锌无机物组合使用，用于治疗关节炎的报道。
发明内容
本发明的目的在于提供一种防治关节炎的药物组合物，以解决现有药物疗效不佳、药物需口服、刺激胃肠道粘膜产生不良反应的问题。
本发明提供了一种防治关节炎的药物组合物，它是由下述原料药制备而成的制剂：含硒无机化合物、含锌无机化合物。
进一步的，它是由下述重量配比的原料药制备而成的制剂：含锌无机化合物1份～5份、含硒无机化合物1份～5份。
优选的，它是由下述重量配比的原料药制备而成的制剂：含锌无机化合物3份、含硒无机化合物3份。
进一步的，所述的含锌无机化合物选自硫酸锌、氯化锌或乙酸锌中的一种或几种；所述的含硒无机化合物为亚硒酸钠。
其中，所述的制剂由各重量配比的原料药，加上药学上可接受的辅料或辅助性成份制备而成。
进一步的，所述的制剂为外用制剂。
优选的，所述的制剂选自凝胶剂、乳膏剂、软膏剂或贴剂。
本发明提供了一种所述的药物组合物的制备方法，其特征是：包含下述步骤：称取各重量配比的原料药，加入药学上可接受的辅料或辅助性成份，即得。
本发明还提供了所述的药物组合物在制备治疗和/或预防关节炎的药物中的用途。
进一步的，所述的药物是治疗和/或预防骨关节炎、风湿性关节炎、类风湿关节炎、痛风性关节炎、反应性关节炎、感染性关节炎、创伤性关节炎、腕管综合症、粘液囊炎中一种或几种疾病的药物。
优选的，所述的药物是治疗和/或预防骨关节炎的药物。
本发明提供了一种防治关节炎的药物组合物。该药物组合物可制备成外用制剂，针对各种关节疼痛提供了更为快速、安全的治疗手段。虽然硒盐对关节炎症具有一定的治疗效果，但是无机硒盐外用很难转运到炎性细胞内，而本发明药物组合物巧妙地解决了这个问题。药效实验证明，本发明药物组合物可以显著降低关节炎模型的关节冲洗液中炎性细胞因子的水平，其软膏剂甚至能达到优于扶他林软膏的疗效，具有良好的临床应用前景。
显然，根据本发明的上述内容，按照本领域的普通技术知识和惯用手段，在不脱离本发明上述基本技术思想前提下，还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
具体实施方式
本发明具体实施方式中使用的原料、设备均为已知产品，通过购买市售产品获得。
实施例1本发明药物组合物凝胶剂的制备
处方：硫酸锌0.10g，亚硒酸钠0.10g，卡波姆940 10g，甘油75g，聚山梨酯80 2g，三乙醇胺13.5g，蒸馏水加至1000g。
工艺：将卡波姆940与聚山梨酯80及300g蒸馏水混合，另取三乙醇胺溶于100g蒸馏水后加入前述溶液中搅匀，再加入甘油搅匀，即得基质。取硫酸锌和亚硒酸钠溶于蒸馏水250g中，全溶后加入上述基质中，加水至全量,搅拌均匀，除去气泡，即得凝胶剂ZJ-1。
实施例2本发明药物组合物凝胶剂的制备
处方：硫酸锌0.5g，亚硒酸钠0.1g，卡波姆940 10g，甘油75g，聚山梨酯80 2g，三乙醇胺13.5g，蒸馏水加至1000g。
工艺：将卡波姆940与聚山梨酯80及300g蒸馏水混合，另取三乙醇胺溶于100g蒸馏水后加入前述溶液中搅匀，再加入甘油搅匀，即得基质。取硫酸锌和亚硒酸钠溶于蒸馏水250g中，全溶后加入上述基质中，加水至全量,搅拌均匀，除去气泡，即得凝胶剂ZJ-2。
实施例3本发明药物组合物乳膏剂的制备
处方：硫酸锌0.5g，亚硒酸钠0.5g,白凡士林100g，十八醇100g，液体石蜡50g，单硬脂酸甘油酯60g，OP乳化剂(烷基酚聚氧乙烯醚)10g，平平加O 20g，甘油50g，月桂氮卓酮20g。
工艺：取白凡士林，十八醇，单硬脂酸甘油酯，液体石蜡，平平加O，混合，加热至80度溶解，得油相。取氯化锌，月桂氮卓酮，亚硒酸钠，甘油，OP乳化剂加水300ml，搅拌均匀，加入油相，保温乳化20分钟，加水至1000ml，即得乳膏剂ZJ-3。
实施例4本发明药物组合物软膏剂的制备
处方：硫酸锌0.1g，亚硒酸钠0.5g，硬脂酸120g，单硬脂酸甘油酯30g，液体石蜡50g，凡士林12g，羊毛脂40g，三乙醇胺3g，尼泊金乙酯1g，加蒸馏水至1000g。
工艺：取硬脂酸、单硬脂酸甘油酯、液体石蜡、凡士林、羊毛脂混合加热熔化；另取硫酸锌和亚硒酸钠、三乙醇胺、尼泊金乙酯、加蒸馏水，加热混匀，慢慢倒入前述硬脂酸等的混合物中，搅拌至乳化凝结，即得软膏剂ZJ-4。
实施例5本发明药物组合物贴剂的制备
处方：硫酸锌0.3g，亚硒酸钠0.3g，明胶60g，纤维素钠100g，聚丙烯酸钠30g，高岭土120g，PEG400(聚乙二醇400)80g，卡波姆100g，山梨 醇20g，甘油200g，水290g。
工艺：取各原辅料，混合，搅拌均匀，加无纺布，背衬层，防粘层，即得贴剂ZJ-5。
实施例6本发明药物组合物凝胶剂的制备
处方：氯化锌0.5g，亚硒酸钠0.1g，卡波姆940 10g，甘油75g，聚山梨酯80 2g，三乙醇胺13.5g，蒸馏水加至1000g。
工艺：将卡波姆940与聚山梨酯80及300g蒸馏水混合，另取三乙醇胺溶于100g蒸馏水后加入前述溶液中搅匀，再加入甘油搅匀，即得基质。取硫酸锌和亚硒酸钠溶于蒸馏水250g中，全溶后加入前述基质中，加水至全量，搅拌均匀，除去气泡，即得凝胶剂ZJ-6。
实施例7本发明药物组合物凝胶剂的制备
处方：乙酸锌0.3g，亚硒酸钠0.3g，卡波姆940 5g，甘油75g，聚山梨酯80 2g，三乙醇胺13.5g，蒸馏水加至1000g。
工艺：将卡波姆940与聚山梨酯80及60g蒸馏水混合，另取三乙醇胺溶于100g蒸馏水后加入前述溶液搅匀，再加入甘油搅匀，即得基质。取硫酸锌和亚硒酸钠溶于蒸馏水50g中，全溶后加入前述基质中，加水至全量，搅拌均匀，除去气泡，即得凝胶剂ZJ-7。
实施例8本发明药物组合物乳膏剂的制备
处方：氯化锌0.1g，亚硒酸钠0.5g，白凡士林100g，十八醇100g，液体石蜡50g，单硬脂酸甘油酯60g，OP乳化剂10g，平平加O 20g，甘油50g，月桂氮卓酮20g。
工艺：取白凡士林，十八醇，单硬脂酸甘油酯，液体石蜡，平平加O，混合，加热至80度溶解，得油相，取氯化锌，月桂氮卓酮，亚硒酸钠，甘油，OP乳化剂加水300ml，搅拌均匀，加入油相，保温乳化20分钟，加水至1000ml，即得乳膏剂ZJ-8。
以下通过对比例和药效实验证明本发明的有益效果。
对比例1锌凝胶剂的制备
处方：硫酸锌0.5g，卡波姆940 10g，甘油75g，聚山梨酯80 2g，三乙醇胺13.5g，蒸馏水加至1000g。
工艺：将卡波姆940与聚山梨酯80及300g蒸馏水混合，另取三乙醇胺溶于100g蒸馏水后加入前述溶液搅匀，再加入甘油搅匀，即得基质。取硫酸锌和亚硒酸钠溶于蒸馏水250g中，全溶后加入前述基质中，加水至全量，搅 拌均匀，除去气泡，即得锌凝胶剂ZN。
对比例2硒凝胶剂的制备
处方：亚硒酸钠0.5g，卡波姆940 10g，甘油75g，聚山梨酯80 2g，三乙醇胺13.5g，蒸馏水加至1000g。
工艺：将卡波姆940与聚山梨酯80及300g蒸馏水混合，另取三乙醇胺溶于100g蒸馏水后加入前述溶液搅匀，再加入甘油搅匀，即得基质。取硫酸锌和亚硒酸钠溶于蒸馏水250g中，全溶后加入上述基质中，加水至全量，搅拌均匀，除去气泡，即得硒凝胶剂SE。
药效实验
炎症的常规生物标记物是细胞因子和趋化因子如TNF-α(肿瘤坏死因子-α)、NF-kB(转录因子蛋白家族)或IL(白介素)等。
实验目的：考察本发明药物组合物对兔膝骨关节炎模型中细胞因子(TNF-α和IL-1β)含量的影响。
材料与方法：
实验材料：实验动物健康新西兰大白兔130只，雌雄各半，体重2.5-3Kg，由成都达硕实验动物有限公司提供。标准饲料喂养，室温15～25℃，每天正常光照，空气流通，自由摄食、饮水。
实验药品：
根据实施例1～8制备的制剂对照药物：扶他林软膏
主要试剂及仪器：
TNF-α放免测定试剂盒；
IL-1β放免测定试剂盒；
电子天平(ME2355型，SARTORIUS公司)，系列可调节移液器及吸头、低速离心机、快速混匀器、兔固定台，冰箱等。
实验方法：
动物分组：130只新西兰大白兔采用单纯随机抽样方法分为13组：空白组、模型组、对照组、ZN组、SE组、治疗组1-8组，每组10只，称重标记。
造模方法：除空白组不造模外，其余12组采用Vandman法将实验动物左膝关节用石膏固定于伸直位。固定范围从兔踝关节下3cm至腹股沟以下1.5cm，踝背屈30-40°，固定时间6周。固定满6周后，将各组动物分别随机处死1只，取关节软骨作病理检查以观察造模情况。造模成功后，去除固定，剃毛。
给药：各组造模成功后，对照组外涂扶他林软膏，厚度约2mm，均匀覆盖造模关节表面，每天2次。治疗组分别外用根据实施例1～8制备的制剂，厚度约2mm，均匀覆盖造模关节表面，每天2次。ZN组外用根据对比例1制备的凝胶剂，SE组外用根据对比例2制备的凝胶剂，厚度约2mm，均匀覆盖造模关节表面，每天2次。模型组外敷凡士林，厚度约2mm，均匀覆盖造模关节，每天2次。空白组亦于右膝关节表面外敷凡士林，厚度约2mm，每天2次。
检测方法：
敷药8周后耳缘静脉处注射空气30ml，快速处死兔，固定于解剖架上，双膝关节快速备皮消毒；取髌韧带附着点外上方约0.5cm处，沿韧带外缘向内向后进针，向关节腔内注射1.5ml蒸馏水，反复吸抽关节液数次后，抽取约2ml关节混合液，将关节混合液置4000r/min离心10min，吸出上清液约0.3ml，装入试管中，置-20℃低温冰箱保存待测，关节冲洗液中TNF-α和IL-1β含量按试剂盒内含量按试剂盒内说明书进行测定。
统计学方法：
实验数据以平均值±标准差(x±s)表示，采用t或t’检验进行组间两两比较，检验水准α＝0.05，运用SPSS 17.0软件进行分析。
实验结果
表1本发明药物组合物对兔膝骨关节炎模型关节液中细胞因子TNF-α和IL-1β含量的影响
Figure PCTCN2016099076-appb-000001
空白组关节冲洗液中TNF-α、IL-1β含量低于模型组，有显著性差异(P<0.01)，说明造模后兔左膝关节液中炎性细胞因子增高。
对照组、治疗组关节冲洗液中TNF-α、IL-1β含量比模型对照组低，有显著性差异(P<0.01)，说明本发明药物组合物可以显著降低关节炎模型的关节冲洗液中炎性细胞因子的水平。
单用含硒凝胶剂或者单用含锌凝胶剂，关节冲洗液中TNF-α、IL-1β含量与模型组相比无显著性差异，说明单用硒或锌治疗关节炎的抗炎效果较差，而仅有本发明含硒无机物、含硒无机物在特定配比下组合使用，才能达到理想的抗炎效果。
以上实验结果表明：本发明药物组合物对关节炎具有显著的治疗效果，其中贴剂ZJ-5甚至能达到明显优于扶他林软膏的疗效。

Claims (11)

  1. 一种防治关节炎的药物组合物，其特征是：它是由下述原料药制备而成的制剂：含硒无机化合物、含锌无机化合物。
  2. 如权利要求1所述的药物组合物，其特征是：它是由下述重量配比的原料药制备而成的制剂：含锌无机化合物1份～5份、含硒无机化合物1份～5份。
  3. 如权利要求2所述的药物组合物，其特征是：它是由下述重量配比的原料药制备而成的制剂：含锌无机化合物3份、含硒无机化合物3份。
  4. 如权利要求1-3任意一项所述的药物组合物，其特征是：所述的含锌无机化合物选自硫酸锌、氯化锌或乙酸锌中的一种或几种；所述的含硒无机化合物为亚硒酸钠。
  5. 如权利要求1-4任意一项所述的药物组合物，其特征是：所述的制剂由各重量配比的原料药，加上药学上可接受的辅料或辅助性成份制备而成。
  6. 如权利要求5所述的药物组合物，其特征是：所述的制剂为外用制剂。
  7. 如权利要求6所述的药物组合物，其特征是：所述的制剂选自凝胶剂、乳膏剂、软膏剂或贴剂。
  8. 一种权利要求1-7任意一项所述的药物组合物的制备方法，其特征是：包含下述步骤：称取各重量配比的原料药，加入药学上可接受的辅料或辅助性成份，即得。
  9. 权利要求1-7任意一项所述的药物组合物在制备治疗和/或预防关节炎的药物中的用途。
  10. 如权利要求9所述的用途，其特征是：所述的药物是治疗和/或预防骨关节炎、风湿性关节炎、类风湿关节炎、痛风性关节炎、反应性关节炎、感染性关节炎、创伤性关节炎、腕管综合症、粘液囊炎中一种或几种疾病的药物。
  11. 如权利要求10所述的用途，其特征是：所述的药物是治疗和/或预防骨关节炎的药物。
PCT/CN2016/099076 2015-12-14 2016-09-14 一种防治关节炎的药物组合物及其制备方法 WO2017101536A1 (zh)

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