CN1471916A - 用于治疗浅部真菌的含联苯苄唑的药物组合物 - Google Patents

用于治疗浅部真菌的含联苯苄唑的药物组合物 Download PDF

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CN1471916A
CN1471916A CNA031337171A CN03133717A CN1471916A CN 1471916 A CN1471916 A CN 1471916A CN A031337171 A CNA031337171 A CN A031337171A CN 03133717 A CN03133717 A CN 03133717A CN 1471916 A CN1471916 A CN 1471916A
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bifonazole
superficial mycosis
triamcinolone acetonide
medicnial
lambral
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CN1179724C (zh
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艳 王
王艳
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Liaoning Shengsheng Pharmaceutical Group Co., Ltd.
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LIAONING DASHENG PHARMACEUTICAL Ltd
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Abstract

本发明提供了一种治疗浅部真菌的药物组合物,该组合物中含有联苯苄唑和醋酸曲安奈德,用于治疗浅部真菌感染的同时具有抗炎、抗过敏及止痒的双重作用。

Description

用于治疗浅部真菌的含联苯苄唑的药物组合物
[技术领域]
本发明涉及一种治疗浅部真菌的药物组合物。该组合物含有抗浅部真菌的联苯苄唑和抗炎、抗过敏及止痒的醋酸曲安奈德。
[背景技术]
长期以来,皮肤病专家就指出过糖皮质类激素与抗真菌药结合治疗真菌感染的皮肤病及类似疾病是有益的。临床研究还证明抗真菌药与糖皮质激素类药结合用药加速了病情的临床缓解并改善了杀真菌作用。因此,本发明提供了含有联苯苄唑作为抗真菌药和醋酸曲安奈德作为抗炎、抗过敏及止痒药。
[发明内容]
联苯苄唑是咪唑衍生物,抗菌谱广,对90%的致病真菌有抑制作用,其能抑制多种皮肤真菌(例如毛癣菌属、小孢子菌属)、酵母菌(例如念球菌属、瓶形酵母菌、光滑球拟酵母菌)、霉菌(例如曲霉属)和各种真菌(例如球孢子菌属、芽生菌属、组织胞浆菌属)。它还具有某些革兰阳性细菌(例如葡萄球菌属、链球菌属等)活性。联苯苄唑抑菌机制为:低浓度时阻止细胞膜脂质成分麦角甾醇合成,高浓度时使细胞膜脂质特异性结合膜的性质发生变化,使细胞膜结构及机能发生障碍而显示抗真菌作用。通常用联苯苄唑局部制剂治疗的一些浅层真菌病是股癣、脚癣、手癣、念珠菌病、杂色糠疹和甲真菌病。还发现患有酒渣鼻、牛皮癣、Sebopsoriasis和皮脂溢性皮炎的患者症状改善(HF Doering,Dermatologica169(suppl):125-134,1984;GP Ford等人,ibid169(suppl):135-140,1984),。
醋酸曲安奈德外用具有抗炎、抗过敏及止痒作用,且作用强而持久,能消除局部非感染性炎症引起的发热、发红及肿胀,临床上主要用于过敏性皮炎、湿疹、神经性皮炎、脂溢性皮炎及瘙痒症。
至今从未有人将联苯苄唑与醋酸曲安奈德有效地结合起来使用,以提供消炎活性及快速缓解真菌感染症状的双重作用。现在本申请提出将有效量的联苯苄唑与醋酸曲安奈德结合并制成组合物,可以获得高度的功效和耐受性。
[具体实施方式]
以下将说明本发明中较好的实例,但并不打算对本发明的范围加以任何限制。
实施例1:
    联苯苄唑                   100g
    醋酸曲安奈德               10g
    卡波姆980NF                150g
    1,2-丙二醇                2000g
    去离子水                   2400g
    聚乙二醇400(PEG 400)       3000g
    三乙醇胺                   适量
    乙醇加至                   10000g
制备方法:称取联苯苄唑和醋酸曲安奈德,加入处方量一半的聚乙二醇400和丙二醇,以及适量无水乙醇,加热溶解;称取处方量的卡波姆(Carbopol 980NF),快速搅拌条件下将其逐渐加入去离子水中,使之充分溶胀;加入处方量一半的聚乙二醇400和丙二醇,搅拌混合均匀后,加入适量三乙醇胺的乙醇溶液,搅拌均匀,形成澄清、透明的凝胶;在缓慢搅拌条件下,将药物溶液缓慢加入卡波姆凝胶中,加入乙醇至处方重量,搅拌均匀后灌封、包装。
实施例2:
    联苯苄唑                     100
    醋酸曲安奈德                 10g
    1,2-丙二醇                  800g
    硬脂酸                       600g
    十六醇                       600g
    液状石蜡                     1200g
    单硬脂酸甘油酯               600g
    月桂醇硫酸钠                 100g
    尼泊金乙酯                   10g
    加水至                       10000g
制备方法:取十六醇、液状石蜡、硬脂酸、单硬脂酸甘油酯,80℃加热至熔融并保持温度(I);将月桂醇硫酸钠加入去离子水中,80℃加热溶解(II);联苯苄唑和醋酸曲安奈德加入丙二醇中,加热至溶解(III)。将II在搅拌下加入I中,至形成乳膏;持续搅拌下,将III加入上述乳膏中,持续搅拌直至冷却后,灌封、包装。比较实施例3:
将本发明的复方联苯苄唑(联苯苄唑——醋酸曲安奈德组合物)与市售产品联苯苄唑乳膏(德国拜耳医药保健有限公司生产)进行比较。
将健康白色豚鼠8只,雌雄兼用,试验前一天双侧背部脱毛4×4cm2,用无菌砂纸磨损皮肤1.5×1.5cm2,将108CFU/ml菌悬液20μl涂于破损组织,均匀分布,感染7天后给药,按破损面积及皮屑分布情况随机分组,每组4只(8个部位),每只两个感染给药部位给同一种药,每天观察感染部位的病变情况,并给予评分,连续观察14天,用t检验比较组间差异,结果见表1。另取感染部位的皮屑少许进行培养,计算石膏样毛癣菌转阴率;用x2检验比较组间差异,结果见表2。
表1复方联苯苄唑对“石毛”菌感染部位皮损病变的影响组别           动物数             反损部位病变级分(分,X±SD)联苯苄唑         8                         2.38±0.92复方联苯苄唑     8                         1.50±0.76
    表2复方联苯苄唑对“石毛”菌感染的作用组别        感染部位(个)              转阴动物数联苯苄唑         8                         5复方联苯苄唑     8                         8
表1、2结果表明,复方联苯苄唑对皮肤石膏样毛癣菌感染有明显的治疗作用。复方联苯苄唑对皮肤石膏样毛癣菌感染的治疗作用明显优于单方联苯苄唑。2、对红色毛癣菌感染的治疗作用
健康白色豚鼠8只,雌雄兼用,体重200g左右,试验前一天双侧背部脱毛4×4cm2,用无菌砂纸磨损皮肤1.5×1.5cm2,将108CFU/ml红色毛癣菌悬液20μ1涂于破损组织,均匀分布,感染7天,按破损面积及皮屑分布情况随机分为2组,每组4只(8个感染部位),每只两个感染部位给同一种药,给药治疗14天,每天观察感染部位的病变情况,并给予评分(标准同实验1),用t检验比较组间差异,结果见表3。
   表3复方联苯苄唑对“红毛”菌感染部位皮损病变的影响组别              动物数           皮损部位病变级分(分;X±SD)联苯苄唑            8                      1.88±0.83复方联苯苄唑        8                      1.13±0.83
表3结果表明,复方联苯苄唑乳膏对皮肤红色毛癣菌感染有显著的治疗作用,复方联苯苄唑对红色毛癣菌感染动物的治疗作用明显优于单方联苯苄唑。(二)止痒作用
健康豚鼠20只,体重200~300g,随机分为2组,每组10只。(1)联苯苄唑组(2)复方联苯苄唑组。实验前一天给各组豚鼠右后足剃毛,给药一次,实验当日,用粗纱纸擦伤右后足剃毛处,面积1cm2,局部再涂药一次,对照组给予等量基质,末次给药后10分钟,开始在创面处滴0.01%磷酸组织胺0.05ml/只,以后每隔3分钟依次0.01%,0.02%,0.03%,0.04%……递增浓度,每次均为0.05ml/只,直至出现豚鼠回头舔右后足,以最后出现豚鼠回头舔右后足时所给与的磷酸组织胺总量为致痒阈,记录并比较各组的致痒阈,结果见表4。
    表4复方联苯苄唑乳膏的止痒作用组别            动物数     致痒阈X±SD(磷酸组织胺总量μg)联苯苄唑          10                37.5±18.59复方联苯苄唑      10                218.0±71.34**
表4结果表明,复方联苯苄唑与联苯苄唑比较其致痒阈明显提高,有显著的止痒作用。
以上实验证明,(1)复方联苯苄唑动物局部给药对石膏样毛癣菌所致皮肤感染,可明显减轻局部皮损病变的程度,提高石膏样毛癣菌的转阴率;明显减轻红色毛癣菌致皮肤感染的皮损病变程度,有明显的抗浅部真菌作用。(2)复方联苯苄唑明显提高豚鼠对磷酸组织胺所致的止痒阈,有明显的止痒作用。(3)复方联苯苄唑明显强于单方联苯苄唑。
本领域专业人员都知道,本发明不限于上述说明性实施例的那些细节,并且在不背离其基本特征的条件下本发明也可以以其它具体形式体现,因此我们认为本发明的具体实施方案和实施例总的来说是说明性的、而不是限制性的,保护范围按照所附权利要求书而不是上述说明确定,因此所有在权利要求的含义及其等同范围内的变化都应包括在本发明范围中。

Claims (4)

1、一种治疗浅部真菌的含有联苯苄唑的药物组合物,它的制剂中含有:
a)联苯苄唑作为杀真菌药;
b)醋酸曲安奈德作为抗炎、抗过敏及止痒药。
2、根据权利要求1所述的药剂,其特征在于该制剂是由联苯苄唑、醋酸曲安奈德二种主要成分组成。
3、根据权利要求1的组合物,用于治疗浅部真菌引起的皮肤病。
4、根据权利要求1的组合物,其中可药用剂型是外用剂型。
CNB031337171A 2003-07-11 2003-07-11 用于治疗浅部真菌的含联苯苄唑的药物组合物 Expired - Fee Related CN1179724C (zh)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110118220A1 (en) * 2009-11-13 2011-05-19 Fibonacci Biological Medicine, LLC Composition of bifonazole and its use
CN102670622A (zh) * 2012-04-26 2012-09-19 辽宁盛生医药集团有限公司 用于治疗浅部真菌的含联苯苄唑的药物组合物
CN108926557A (zh) * 2018-07-06 2018-12-04 泮宝峰 一种含有植物提取物的抗耐药真菌的外用组合物
CN108926558A (zh) * 2018-07-06 2018-12-04 泮宝峰 含有一种蜂斗菜提取物的抗耐药真菌外用组合物
CN108992441A (zh) * 2018-07-06 2018-12-14 泮宝峰 复方联苯苄唑外用组合物

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110118220A1 (en) * 2009-11-13 2011-05-19 Fibonacci Biological Medicine, LLC Composition of bifonazole and its use
CN102670622A (zh) * 2012-04-26 2012-09-19 辽宁盛生医药集团有限公司 用于治疗浅部真菌的含联苯苄唑的药物组合物
CN108926557A (zh) * 2018-07-06 2018-12-04 泮宝峰 一种含有植物提取物的抗耐药真菌的外用组合物
CN108926558A (zh) * 2018-07-06 2018-12-04 泮宝峰 含有一种蜂斗菜提取物的抗耐药真菌外用组合物
CN108992441A (zh) * 2018-07-06 2018-12-14 泮宝峰 复方联苯苄唑外用组合物

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