CN107684552A - 一种依托芬那酯贴剂 - Google Patents

一种依托芬那酯贴剂 Download PDF

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CN107684552A
CN107684552A CN201611137932.6A CN201611137932A CN107684552A CN 107684552 A CN107684552 A CN 107684552A CN 201611137932 A CN201611137932 A CN 201611137932A CN 107684552 A CN107684552 A CN 107684552A
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etofenamate
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dodecyl amine
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CN107684552B (zh
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李培耀
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Anhui Tianyun Medical Equipment Co Ltd
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    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions

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Abstract

本发明涉及一种依托芬那酯贴剂，属于药物制剂领域。本发明的依托芬那酯贴剂的载药层包括依托芬那酯，并且包含由0.5‑10％的十二烷胺和0.1‑4％木瓜蛋白酶组成的促渗剂，载药层还包括表面活性剂、乳化剂、保湿剂、防腐剂或抗氧剂等和作为余量的硅酮压敏胶，另外，还包括背衬层和防粘层。结果显示，本发明的依托芬那酯贴剂与市售依托芬那酯市售凝胶相比，对小鼠醋酸致炎引起的扭体抑制百分率更好，说明其消炎镇痛效果更佳。

Description

一种依托芬那酯贴剂
技术领域
本发明涉及药物制剂领域，具体涉及一种依托芬那酯贴剂。
背景技术
依托芬那酯(Etofenamate)属灭酸类非甾体类抗炎药，可抑制环氧化酶和酯氧化酶，减少前列腺素和其他炎症介质的作用，从而发挥抗炎、镇痛作用。涂于皮肤上可被透皮吸收，且其药物活性成分能有效地转移到炎症部位，减轻局部肿胀并有较好的耐受性。实验动物口服后，其抗炎作用优于氟芬那酸和保泰松，但有一定的致消化道溃疡的不良反应。可抑制缓激肽、环氧化酶、组胺、5-羟色胺、透明质酸和总补体的释放和作用，稳定溶酶体膜，使用300mg，12～14h后血药浓度达峰值，蛋白结合率为98％～99％，通过肾和粪便，以氢氧化物、醚裂解物等形式排出。生物利用度有高度的个体差异，同一个体也因用药部位、皮肤湿度不同而有较大差异，相对生物利用度与其他含有依托芬结构的药物相似(大于20％)。
依托芬那酯具有极强的亲酯性及一定的亲水性，故有良好的透皮功能，故专供外用。局部使用本药300mg，12～14h后血药浓度达峰值，蛋白结合率为98％～99％。可分布在人的血液、尿液、滑液、滑膜组织中。对炎症部位、滑膜组织、滑液有高亲和性(比非炎症部位高5～20倍)，其中滑膜组织中的浓度是血浆浓度的50％。
依托芬那酯局部运用，适用于骨骼肌肉系统中各种急慢性疾病的对症治疗，如各种慢性关节炎、肌软组织炎、闭合性外伤等。用于骨骼肌肉系统的软组织风湿性疾病，如肌肉风湿症、肩痛及僵硬、肌肉痉挛(肩关节周围炎的关节周围痛)、腰痛、坐骨神经痛、腱鞘炎、滑囊炎以及过度劳累或退行性病变所致脊柱病和关节病、外伤如挫伤、扭伤和劳损。
现有技术中虽然存在依托芬那酯的贴剂，但是效果一般。
发明内容
本发明的目的即是克服现有技术的不足，提供一种效果优异的依托芬那酯的贴剂。
本发明解决该技术问题的技术方案是：
一种依托芬那酯贴剂，载药层包括依托芬那酯，并且包含由0.5-10％的十二烷胺和0.1-4％木瓜蛋白酶组成的促渗剂。
所述十二烷胺的含量优选为4-8％，木瓜蛋白酶的含量优选为1-4％。
所述载药层还包括表面活性剂、乳化剂、保湿剂、防腐剂或抗氧剂等，还包括作为余量的硅酮压敏胶。
本发明的依托芬那酯凝贴剂还包括背衬层和防粘层。
结果显示，本发明的依托芬那酯贴剂与市售依托芬那酯市售凝胶相比，对小鼠醋酸致炎引起的扭体抑制百分率更好，说明其消炎镇痛效果更佳。
具体实施方式
实施例1
将依托芬那酯5％、十二烷胺4％、木瓜蛋白酶4％和硅酮压敏胶基质混合均匀，涂布于防粘层上，干燥后与背衬层复合，切割成贴剂。
实施例2
将依托芬那酯4％、十二烷胺6％、木瓜蛋白酶2％和硅酮压敏胶基质混合均匀，涂布于防粘层上，干燥后与背衬层复合，切割成贴剂。
实施例3
将依托芬那酯5％、十二烷胺8％、木瓜蛋白酶1％和硅酮压敏胶基质混合均匀，涂布于防粘层上，干燥后与背衬层复合，切割成贴剂。
实施例4
将依托芬那酯6％、十二烷胺5％、木瓜蛋白酶3％和硅酮压敏胶基质混合均匀，涂布于防粘层上，干燥后与背衬层复合，切割成贴剂。
对比例1
将依托芬那酯5％、十二烷胺8％和硅酮压敏胶基质混合均匀，涂布于防粘层上，干燥后与背衬层复合，切割成贴剂。
对比例2
将依托芬那酯5％、木瓜蛋白酶8％和硅酮压敏胶基质混合均匀，涂布于防粘层上，干燥后与背衬层复合，切割成贴剂。
试验例一：本发明的依托芬那酯贴剂的体外经皮渗透实验
采用立式扩散池，有效扩散面积为2.8cm2，所用皮肤为去毛猪耳朵皮肤，皮肤厚度约为约600μm。将贴剂贴于去毛猪耳朵皮肤的角质层一侧，置于扩散池与接收池之间，角质层朝向扩散池，真皮层朝向接收池。接收池体积为6.5mL，加满pH7.4磷酸缓冲液并排除气泡，置于循环水浴磁力搅拌池中，磁子转速设为300r/min，水浴温度为37℃。透皮开始后第2h、4h、6h、8h、10h、12h、14h、24h取样1mL，取样后立即补充新鲜的接收液，将取样液用0.45μm微孔滤膜滤过后用高效液相色谱法测定双氯芬酸钠的浓度，分别以实施例1-4和对比例1-2的贴剂进行试验，计算经皮渗透速率和累积渗透量，结果如表1所示。
表1本发明的依托芬那酯贴剂的经皮渗透效果(n＝3)
组别 经皮渗透速率(μg·cm-2·h-1) 累积渗透量(μg·cm-2)
实施例1 1.34±0.12 21.21±1.11
实施例2 1.45±1.23 22.11±1.22
实施例3 1.61±0.77 24.07±0.89
实施例4 1.44±0.29 21.34±0.54
对比例1 0.52±0.12 9.47±1.14
对比例2 0.48±0.33 9.26±0.76
结果显示，本发明的依托芬那酯贴剂采用十二烷胺和木瓜蛋白酶作为促渗剂，能够很好的提高依托芬那酯的经皮渗透速率和累积渗透量，与单用十二烷胺或木瓜蛋白酶相比具有显著的技术进步。
试验例二：本发明的依托芬那酯贴剂的消炎镇痛效果试验
将60只18-22g的昆明种雌性小鼠随机分为空白组、依托芬那酯市售凝胶阳性对照组、实施例1-4的依托芬那酯贴剂组，每组10只。空白组不做任何处理，贴剂组在小鼠腹部脱毛部位给予1cm2上述贴剂。给药30min后腹腔注射给予醋酸溶液(1.5％，0.1ml/10g)，当小鼠腹部凹陷，同时躯干与后肢伸张、身体扭曲时视为出现扭体反应。从注射醋酸后开始计时，记录小鼠开始扭体的时间与20min内扭体的次数，并计算扭体抑制百分率(PIP)，PIP＝(空白组扭体次数均值－给药组扭体次数均值)/空白组扭体次数均值×100％。
表2本发明的依托芬那酯贴剂的消炎镇痛效果
20min内扭体次数 扭体抑制百分率(PIP)
空白组 28.32±2.14 —
阳性对照组 10.12±3.14 81.04％
实施例1组 8.03±3.21 93.24％
实施例2组 7.25±1.52 95.01％
实施例3组 7.08±2.03 98.11％
实施例4组 7.14±3.54 96.11％
结果显示，本发明的依托芬那酯贴剂与市售依托芬那酯市售凝胶相比，对小鼠醋酸致炎引起的扭体抑制百分率更好，说明其消炎镇痛效果更佳。

Claims (5)

1.一种依托芬那酯贴剂，其特征在于，载药层包括依托芬那酯，并且包含由0.5-10％的十二烷胺和0.1-4％木瓜蛋白酶组成的促渗剂。
2.根据权利要求1所述的依托芬那酯贴剂，其特征在于，所述十二烷胺的含量优选为4-8％，木瓜蛋白酶的含量优选为1-4％。
3.根据权利要求1-2任一项所述的依托芬那酯贴剂，其特征在于，载药层还包括表面活性剂、乳化剂、保湿剂、防腐剂或抗氧剂等。
4.根据权利要求1-3任一项所述的依托芬那酯贴剂，其特征在于，载药层还包括作为余量的硅酮压敏胶。
5.根据权利要求1-4任一项所述的依托芬那酯贴剂，其特征在于，还包括背衬层和防粘层。
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