CN105999273A - 一种用于关节炎治疗的复方制剂 - Google Patents
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Abstract
本发明公开了一种用于关节炎治疗的复方制剂,其选择基于透明质酸的温敏性高分子材料为药物载体,包载非甾体抗炎药物和活性多肽物质。载体材料具有温敏性,在室温或温度低于体温时,制剂为流动的液体状态,便于注射,当注射至关节腔后,制剂纳米混悬液转变成凝胶。这不但可以控制药物释放,而且还可以使载体、药物和多肽发挥协同作用,提高治疗效果。
Description
技术领域
本发明属于医药技术领域,提供了一种用于关节炎治疗的复方制剂。
背景技术
非甾体抗炎药(NSAIDs)已广泛应用关节炎的治疗,它主要是通过抑制环氧化酶(COX),从而抑制前列腺素的合成达到消炎止痛的疗效。但是目前临床上使用的NSAIDs以口服制剂为主,患者长期服用容易产生胃肠道不良反应,并对肝脏、肾脏和心血管等存在一定的损害。
细胞因子在骨性关节炎的发病过程中占重要地位,它可以加速软骨基质的分解代谢,加重软骨退变。因此,多肽类药物可以降低细胞因子活性,治疗关节炎。鹿瓜多肽是一类治疗关节炎的多肽类生物活性物质,主要含有骨形态发生蛋白、转化生长因子β、成纤维细胞生长因子等多肽类因子。它不但能缓解炎症反应的破坏性,而且能在组织修复中发挥作用。鹿茸多肽对软骨细胞有明显的促增殖分裂活性,有利于促进伤口愈合,发挥抗炎作用。因此,多肽活性药物与非甾体抗炎药联合使用可以提高关节炎的治疗效果。
关节腔注射给药可以将药物直接作用于靶部位,提高局部浓度,避免体内生理转运屏障,改变药物的分布模式,以小剂量发挥药效,降低全身给药的毒副作用,因此在关节炎的治疗中具有广泛地应用。这种制剂具有多种优势:缓释长效;可降低药物在关节腔的清除率;可减少大剂量药物的刺激性;可避免反复给药的感染;药物仅需在注射部位有活性,降低毒副作用等。该类制剂数日甚至数月注射一次,显著增强药物有效性与安全性,提高患者顺应性。专利CN100594029、CN101112378和CN101940587B等均公开了关节腔内注射给药治疗关节炎的方法。
温度敏感型原位凝胶是一种依赖温度而发生相转变的凝胶。它在储藏条件下是自由流动的液体,注射进入人体后可填充于组织间隙,迅速发生相转变,在注射部位形成半固体状态凝胶,达到局部给药或延缓药物释放的目的。它具有可注射、创伤小、给药方便、控制药物释放等优点,适用于体内局部注射给药。普洛沙姆(Poloxamer)是研究最深入的制备温度敏感原位凝胶的高分子材料。目前专利和文献资料报道的温敏凝胶的主要基质材料多为普洛沙姆407(商品名为F127),如CN1230108A、CN101185650A、CN1593386A、CN1377706A、CN100422268C、CN02109503.5等。其中,浓度为20%-30%的F127水溶液具有受热反向胶凝的性质,即冷藏温度下是自由流动的液体,而室温或体温时形成澄明的凝胶。
透明质酸关节腔注射给药是治疗关节炎的常用方法。目前临床常用的透明质酸关节腔注射剂有Hyalgan、Artz、NRD-101、Hylan G-F20等。其中,Hylan G-F20为美国Genzyme公司生产的透明质酸凝胶注射液。专利CN02822420.5、US2006003964和CN101112381A均公开了透明质酸用于关节腔内给药治疗关节炎的方法。但是仅注射单一的透明质酸普通凝胶注射剂还存在一定的缺陷,如体内滞留时间短,易被HA酶降解;体外形成凝胶后注射,使用具有一定难度;没有包载治疗药物、起效较慢等。因此,对透明质酸进行结构修饰,制备包载药物的缓释制剂显得尤为重要。文献等也研究报道了透明质酸和NSAIDs组合治疗能迅速改善关节炎患者的临床症状,并且在维持良好疗效的同时,能显著降低NSAIDs的用量。
发明内容
本发明的目的是提供一种用于关节炎治疗的复方制剂,以达到降低药物不良反应,减少给药次数,发挥协同作用,更好地治疗关节炎。本发明复方制剂由温敏性载体材料、非甾体抗炎药物和活性多肽物质组成。
上述的温敏性载体材料由透明质酸与其它材料组成,其中,包括普洛沙姆、胶原、聚乳酸-羟基乙酸、壳聚糖或异丙基丙烯酰胺的一种或几种组合。
上述的温敏性载体材料是透明质酸通过化学键结合或者物理方式混合使用。
上述的温敏性载体材料中,透明质酸的分子量为50万-500万道尔顿,优选70万–200万道尔顿。
上述的温敏性载体材料优选透明质酸-普洛沙姆聚合物。
上述的药物为非甾体抗炎类药物,其中,包括双氯芬酸、美洛昔康、依托度酸、酮洛芬、吲哚美辛、塞来昔布、萘丁美酮、罗非昔布的一种或几种组合。
上述的活性多肽为鹿瓜多肽(包含转化生长因子β、骨形态发生蛋白和成纤维细胞生长因子)和鹿茸多肽等。
上述的药物与多肽共同包裹或分散于载体材料。聚合物的浓度和载药量不受限制,除非影响到聚合物的胶凝行为,使其不能形成凝胶或限制其临床使用。
上述的复方制剂具有温度敏感性质,当温度低于体温时,制剂以液态形式存在,在注射部位温度升高至体温,制剂由转变成凝胶,延长药物的释放时间。
具体实施方式
以下通过具体实施例来对本发明进行更详细的说明,但是本发明的范围并不限于以下实施例。
将透明质酸-普洛沙姆温敏材料悬浮于磷酸盐缓冲液(PBS,pH 7.4)中,探头超声6min(工作功率90W,工作脉冲为工作1s暂停5s),可得空白纳米凝胶混悬液。将塞来昔布溶于少量DMF溶液中,温敏材料及活性多肽溶于PBS中,搅拌混合后,PBS缓冲液(pH 7.4)透析12h,离心取上清液,过滤后冻干,制得复方制剂。
Claims (9)
1.一种用于关节炎治疗的复方制剂,其特征在于,该制剂是由温敏性载体材料、非甾体抗炎药物和活性多肽物质组成。
2.根据权利要求1所述的复方制剂,其特征在于,温敏性载体材料由透明质酸与其它材料组成,其中,包括普洛沙姆、胶原、聚乳酸-羟基乙酸、壳聚糖或异丙基丙烯酰胺的一种或几种组合。
3.根据权利要求2所述的温敏材料,其特征在于,透明质酸通过化学键结合或者物理方式混合使用。
4.根据权利要求2所述的温敏材料,其特征在于,透明质酸的分子量为50万-500万道尔顿,优选70万–200万道尔顿。
5.根据权利要求2所述的温敏材料,其特征在于,温敏材料优选透明质酸-普洛沙姆聚合物。
6.根据权利要求1所述的复方制剂,其特征在于,药物为非甾体抗炎类药物,其中,包括双氯芬酸、美洛昔康、依托度酸、酮洛芬、吲哚美辛、塞来昔布、萘丁美酮、罗非昔布的一种或几种组合。
7.根据权利要求1所述的复方制剂,其特征在于,活性多肽为鹿瓜多肽(包含转化生长因子β、骨形态发生蛋白和成纤维细胞生长因子)和鹿茸多肽等。
8.根据权利要求1所述的复方制剂,其特征在于,药物与多肽共同包裹或分散于载体材料。聚合物的浓度和载药量不受限制,除非影响到聚合物的胶凝行为,使其不能形成凝胶或限制其临床使用。
9.根据权利要求1所述的复方制剂,其特征在于,该制剂具有温度敏感性质,当温度低于体温时,制剂以液态形式存在,在注射部位温度升高至体温,制剂由转变成凝胶,延长药物的释放时间。
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109381421A (zh) * | 2017-08-04 | 2019-02-26 | 杨新民 | 温感性可降解的弹性体、其制备方法及其用途 |
CN114432493A (zh) * | 2021-12-23 | 2022-05-06 | 南方医科大学顺德医院(佛山市顺德区第一人民医院) | 一种可注射生物降解温敏水凝胶及其应用 |
WO2024030103A3 (en) * | 2022-07-31 | 2024-03-14 | Istanbul Medipol Universitesi | Formulations comprising hyaluronic acid and cetyl myristoleate and the use of these formulations in the treatment of osteoarthritis |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104208014A (zh) * | 2014-09-17 | 2014-12-17 | 江南大学 | 关节腔注射用温敏型原位凝胶及其制备方法 |
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CN104208014A (zh) * | 2014-09-17 | 2014-12-17 | 江南大学 | 关节腔注射用温敏型原位凝胶及其制备方法 |
Non-Patent Citations (1)
Title |
---|
张惠: "鹿瓜多肽联合美洛昔康治疗老年类风湿性关节炎的疗效观察", 《中国药业》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109381421A (zh) * | 2017-08-04 | 2019-02-26 | 杨新民 | 温感性可降解的弹性体、其制备方法及其用途 |
CN114432493A (zh) * | 2021-12-23 | 2022-05-06 | 南方医科大学顺德医院(佛山市顺德区第一人民医院) | 一种可注射生物降解温敏水凝胶及其应用 |
WO2024030103A3 (en) * | 2022-07-31 | 2024-03-14 | Istanbul Medipol Universitesi | Formulations comprising hyaluronic acid and cetyl myristoleate and the use of these formulations in the treatment of osteoarthritis |
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