CN109381466A - 促进糖尿病病人伤口愈合的治疗剂 - Google Patents
促进糖尿病病人伤口愈合的治疗剂 Download PDFInfo
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Abstract
本发明涉及医药学领域，特别是涉及一种瑞巴派特的医药用途。本发明经动物实验证明瑞巴派特可以有效地促进糖尿病的伤口愈合。本发明还提供一种促进糖尿病病人伤口愈合的药物组合物。
Description
技术领域
本发明涉及用于促进糖尿病病人伤口愈合的含有瑞巴派特的药物组合物。
背景技术
糖尿病是严重威胁人类健康的代谢性疾病，已成为继心血管、肿瘤、艾滋病之后的第四大易致人死亡的疾病。统计数据显示当前全世界有2.85亿糖尿病患者，预测到2030年全世界的糖尿病患者将达到4.39亿，而糖尿病所引发的并发症则成为患者致残和致死的主要原因。在糖尿病的诸多并发症中，糖尿病患者伤口愈合能力受损是糖尿病一个典型的并发症，如果慢性的损伤和溃病发生在足部，则有可能引发糖尿病足，严重者甚至导致截肢，这已成为糖尿病患者住院率最高的疾病，迄今为止尚没有有效的治疗方法。
糖尿病患者，当血糖过高时，细胞内、细胞外都有可能发生脱水，影响伤口愈合。同时，糖尿病患者血糖控制失调，机体抵抗细菌的能力会降低。高血糖导致细胞运输氧到组织的能力降低，血液循环不畅，影响伤口愈合。另一方面，血糖升高易引起微血管病变，损害血管和神经，致使溃病很难愈合。
因此，急需寻求一种能够促进糖尿病病人伤口愈合的治疗药物。
瑞巴派特(Rebamipide)是由日本大冢公司于1990年上市的治疗胃溃疡的药物。研究发现，瑞巴派特具有促进胃黏膜溃疡愈合、消除氧自由基、抗氧化等作用。瑞巴派特的分子式为：C19H15ClN2O4分子量为：370.07，其结构式如下：
发明内容
本发明的目的旨在提供一种瑞巴派特的新的医药用途。本发明人惊奇地发现，瑞巴派特明显促进糖尿病损伤模型表皮再生及肉芽组织的形成。据此，本发明提供了一种瑞巴派特在制备促进糖尿病病人伤口表皮再生及肉芽组织的形成的药物组合物中的应用。
本发明提供了一种瑞巴派特在制备缩短糖尿病病人伤口愈合时间的药物组合物中的应用。
本发明提供了一种瑞巴派特在制备促进糖尿病病人伤口愈合的药物组合物中的应用。
本发明提供了一种瑞巴派特在制备治疗糖尿病足的药物组合物中的应用。
本发明提供了一种瑞巴派特在制备预防糖尿病病人伤口难以愈合的药物组合物中的应用。
本发明提供了一种瑞巴派特在制备预防糖尿病病人伤口难以愈合的药物或食品或化妆品或洗涤用品中的应用。
本发明提供了一种瑞巴派特在制备预防糖尿病足的药物或食品中的应用。
本发明提供了一种瑞巴派特在制备治疗或预防糖尿病坏疽的药物组合物中的应用。
本发明提供了一种瑞巴派特在制备预防糖尿病坏疽的药物或食品或化妆品或洗涤用品中的应用。
本发明的瑞巴派特可以单独使用或以药物组合物的形式使用。本发明提供一种促进糖尿病病人伤口愈合的药物组合物，其特征在于，所述药物组合物中含有治疗有效量的瑞巴派特作为活性成分和药学上可接受的载体。较佳地，本发明的药物组合物含有0.1-99.9％重量百分比的作为活性成分的瑞巴派特。“药学上可接受的载体”不会破坏本发明的瑞巴派特的药学活性，同时其有效用量，即能发挥药物载体作用时的用量对人体无毒。
本发明提供的促进糖尿病病人伤口愈合的药物组合物可用于预防和治疗糖尿病病人的各种表皮损伤，包括糖尿病足、糖尿病口腔溃疡和各种糖尿病皮肤病变。
所述药学上可接受的载体包括但不限于：软磷脂、硬脂酸铝、氧化铝、离子交换材料、自乳化药物传递***、吐温或其他表面活化剂、血清蛋白、缓冲物质如磷酸盐、氨基乙酸、山梨酸、水、盐、电解质如硫酸盐精蛋白、磷酸氢二钠、磷酸氢钾、氯化纳、锌盐、硅酸镁、饱和脂肪酸部分甘油酯混合物等。
其他常用的药物辅料如粘合剂(如微晶纤维素)、填充剂(如淀粉、葡萄糖、无水乳糖和乳糖珠粒)、崩解剂(如交联PVP、交联羧甲基淀粉钠、交联羧甲基纤维素钠、低取代起丙基纤维素)、润滑剂(如硬脂酸镁)以及吸收促进剂、吸附载体、香味剂、甜味剂、赋形剂、稀释剂、润湿剂等。
本发明的瑞巴派特以及其药物组合物可按本领域常规方法制备并可以通过肠道或非肠道或局部途径给药。口服制剂包括胶囊剂、片剂、口服液、颗粒剂、丸剂、散剂、丹剂、膏剂等；非肠道给药制剂包括注射液等；局部给药制剂包括霜剂、贴剂、软膏剂、凝胶剂和喷雾剂等。优选为局部给药制剂。
本发明的瑞巴派特以及其药物组合物的给药途径可以为口服、舌下、经皮、经肌肉或皮下、皮肤粘膜、静脉等。
除了制成药物之外，亦可在本发明的瑞巴派特中加入抗氧化剂、色素、酶制剂等各种食品添加剂，按本领域的常规方法制成保健食品。
附图说明
图1体现了瑞巴派特对db/db小鼠伤口愈合的影响，由图1可见，术后第6天开始至第16天，瑞巴派特给药组db/db小鼠的伤口面积明显小于空白对照组，两者有显著性差异(P＜0.05)。
图2可见，瑞巴派特给药组db/db小鼠伤口平均愈合天数14.8天，显著低于空白对照组(21.2天)(P＜0.001)。
具体实施方式
下面通过实施例具体说明本发明的内容。在本发明中，以下所述的实施例是为了更好的阐述本发明，并不是用来限制本发明的范围。
瑞巴派特可通过商业途径从Sigma化学公司等处购买获得，或者用本领域的常规方法合成。其纯度均符合药用标准。
下列实施例中未注明具体条件的实验方法，通常按照常规条件或按照制造厂商所建议的条件。除非另外说明，否则所有的百分数、比率、比例、或份数按重量计。
除非另行定义，文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外，任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文中所述的较佳实施方法与材料仅作示范之用。
本发明提到的上述特征，或实施例提到的特征可以任意组合。本专利说明书所揭示的所有特征可与任何组合物形式并用，说明书中所揭示的各个特征，可以任何可提供相同、均等或相似目的的替代性特征取代。因此除有特别说明，所揭示的特征仅为均等或相似特征的一般性例子。
实施例1
瑞巴派特对糖尿病损伤模型的促进伤口愈合作用
1、实验材料
1.1药物
瑞巴派特(分子量：370.07，HPLC纯度≥99％，sigma公司)
1.2实验动物
体重50±5g的db/db雌性小鼠(十二周)，由维通利华实验动物中心提供，置于常规饲养环境，分笼饲养，自由进食和饮水。
2、实验方法
2.1糖尿病损伤模型建立
采用义献中的造模方法(Nature Protocols 2013，8：302-309)，异氟烷麻醉后，剃去背部皮肤，脱毛膏脱毛，常规皮肤消毒，使用直径6mm的打孔器分别在背部脊柱两侧切一圆形切口，深达筋膜。为防止伤口自动收缩，分别在其边缘粘上硅胶垫圈(0.5mm thick，内径9mm，外径18mm)，并与皮肤缝合。手术当天计为术后第0天，以此类推。
2.2分组及给药方法
空白对照组：无菌超纯水(15uL/wound)
阳性对照组：血管表皮生长因子(VEGF)(1.0mg/mL，15μL/wound)。
用药组：瑞巴派特(15mg/mL，15uL/wound)。
每组10只，手术当天开始，每两天给药一次，给药后采用生物透性薄膜覆盖伤口。
2.3伤口愈合观察：
手术当天开始，每隔一天，使用数码相机在固定高度采集伤口照片，通过Image J软件计算出伤口面积。
2.4统计分析
所有实验数据均重复3次，结果以平均值±标准差表示，采用SPSS 13.0统计软件对实验数据采用单向方差分析(One-way ANOVA)及LSD检验，P＜0.05为统计学上差异有显著性。
3、结果
3.1瑞巴派特对db/db小鼠伤口愈合的影响。
表1.瑞巴派特对db/db小鼠伤口面积的影响
综上研究结果表明，瑞巴派特可以有效地促进糖尿病小鼠的伤口愈合，显著缩短伤口愈合的时间。
实施例2
药用组合物的制备：片剂
将瑞巴派特(1g)与23g乳糖和5.7g微晶纤维素用混合机混合。用滚轴压紧机将所得混合物压制成型，值得薄片状压制物料。用锤式粉碎机将所述薄片状压制物料研磨成粉，使所得粉状物料通过20目筛过筛。将一份0.3g轻质二氧化硅和0.3g硬脂酸镁加入到已过筛的物料中，并混合。所得混合产物用制片机压片。
实施例3
药用组合物的制备：喷剂
取质量比为1∶0.5瑞巴派特和壳聚糖粉末溶解于75％的乙醇溶液中，采用磁力搅拌机上搅拌混匀，制备药物溶液。取质量比为1∶1.26的聚乙烯吡咯烷酮和甘油粉末溶解于75％的乙醇溶液中，采用磁力搅拌机上搅拌混匀，制备致孔溶液。取聚乙烯醇缩丁醛粉末溶解于75％的乙醇溶液中，采用磁力搅拌机上搅拌混匀，制备成膜溶液。取炉甘石粉末溶解于75％的乙醇溶液中，采用磁力搅拌机上搅拌混匀，制备收敛溶液。将上述药物溶液、致孔溶液、成膜溶液和收敛溶液导入反应釜，充分搅拌均匀，得到A液。向A液中加入水溶性辅酶Q10，充分搅拌溶解，得到B液。向B液中加入海藻酸纳，充分搅拌溶解，形成稳定溶液，即得喷剂。
上述实施例中，聚乙烯醇缩丁醛来源于天津华吕源化工贸易有限公司，聚乙烯吡咯烷酮来源于广州粤美化工，海藻酸纳来源于连云港环宇海藻助剂有限公司，含量20％的水溶性辅酶Q10来源于武汉大华伟业医药化工有限公司。
本发明所涉及的多个方面已做如上阐述。然而，应理解的是，在不偏离本发明精神之前提下，本领域专业人员可对其进行等同改变和修饰，所述改变和修饰同样落入本中请所附权利要求的覆盖范围。
Claims (12)
1.瑞巴派特在制备促进糖尿病病人伤口表皮再生及肉芽组织形成的药物组合物中的应用。
2.瑞巴派特在制备缩短糖尿病病人伤口愈合时间的药物组合物中的应用。
3.瑞巴派特在制备促进糖尿病病人伤口愈合的药物组合物中的应用。
4.瑞巴派特在制备预防或治疗糖尿病病人伤口难以愈合的药物组合物中的应用。
5.瑞巴派特在制备预防或治疗糖尿病病人伤口难以愈合的药物或食品或化妆品或洗涤用品中的应用。
6.瑞巴派特在制备治疗糖尿病足的药物组合物中的应用。
7.瑞巴派特在制备预防糖尿病足的药物或食品或化妆品或洗涤用品中的应用。
8.瑞巴派特在制备治疗或预防糖尿病坏疽的药物组合物中的应用。
9.瑞巴派特在制备预防糖尿病坏疽的药物或食品或化妆品或洗涤用品中的应用。
10.一种促进糖尿病病人伤口愈合的药物组合物，其特征在于，所述药物组合物中含有治疗有效量的瑞巴派特作为活性成分和药学上可接受的载体。
11.如权利要求10的药物组合物，其特征在于，所述糖尿病病人伤口来自糖尿病足、糖尿病口腔溃疡和各种糖尿病皮肤病变。
12.如权利要求10的药物组合物，其特征在于，所述药物组合物是胶囊剂、片剂、口服液、颗粒剂、丸剂、散剂、丹剂、膏剂、注射液、霜剂、贴剂、软膏剂、凝胶剂和喷雾剂。
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| CN112494488B (zh) * | 2020-06-17 | 2022-01-18 | 中国药科大学 | 瑞巴派特的防脱发和生发用途 |
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