CN1414856A - 治疗瘙痒的外用制剂 - Google Patents
治疗瘙痒的外用制剂 Download PDFInfo
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Abstract
止痒用外用制剂,含有阿司匹林作为活性成分,该制剂对瘙痒具有优异的治疗效果而副作用小。
Description
技术领域
本发明涉及具有优异抗瘙痒活性的外用制剂以及治疗瘙痒的方法。更详细地说,本发明涉及具有优异止痒活性的外用制剂,其中含有乙酰水杨酸作为活性成分,并且本发明涉及用所述外用制剂治疗瘙痒的方法。
背景技术
近来,随着生活方式的变化,有强烈瘙痒的疾病例如特应性皮炎、荨麻疹、皮肤瘙痒等迅速增加。此外,被昆虫螫(咬)经常引起非常强的瘙痒。
目前有许多止痒剂例如抗组胺药等出售。如果以口服制剂给药,令人忧虑的是其副作用例如瞌睡、无精打采等。
另一方面,含有抗组胺或非甾族抗炎剂的外用制剂的止痒活性不能令人满意,尤其是含抗组胺的制剂还使人担心其副作用例如皮肤过敏,并且含非甾族抗炎剂的制剂也令人担心其副作用例如皮肤刺激、接触性皮炎等。
此外,尽管主要用于治疗特应性皮炎的类固醇外用非常适用于治疗湿疹、皮肤瘙痒、被昆虫螫伤等,但是这些类固醇不仅仅令人担心其副作用例如皮萎缩、类固醇潮红、毛细血管扩张等,而且在反复使用时,这些类固醇还令人担心其经皮吸收移行到血液中、并可能产生全身性的不良作用。
乙酰水杨酸(下文称之为阿司匹林)具有强的止痛活性、退热活性和抗风湿活性,而其副作用小并且其安全性是优异的。因此,阿司匹林很久以来一直被广泛使用。
近来对含有乙酰水杨酸的外用制剂的应用进行了研究。结果是,在公开的专利说明书中公开了具有优异透皮吸收性质的组合物、新的凝胶制剂、带状制剂和硬膏剂。
此外,阐明了乙酰水杨酸以外用制剂形式的新用途、治疗神经痛的软膏(日本专利公开A3-72426)、治疗皮肤损伤的外用制剂(日本专利公开A9-235232)、治疗血栓形成和预防性治疗癌的经皮给药系统(日本专利公开8-504198)。
然而,没有任何有关用于治疗瘙痒的含阿司匹林的外用制剂及其治疗作用的报道。
发明公开
本发明提供了具有优异止痒活性并且副作用小的外用制剂。
本发明人最早研究并且发现,含乙酰水杨酸作为活性成分的外用制剂副作用小并且具有优异的止痒活性。本发明因此得以完成。
换句话说,本发明人已经制备了用于治疗瘙痒的含乙酰水杨酸的外用制剂,并且当该制剂施于损害部位,例如瘙痒如被昆虫螫咬、受损皮肤、湿疹、皮肤瘙痒、特应性皮炎等的损害部位时,发现了优异的止痒效果。
在日本药典XIII中描述了本发明外用制剂中所含的乙酰水杨酸。
在该外用制剂中乙酰水杨酸的含量取决于制剂的形式,但是总重量的0.05-80%、优选0.05-70%、更优选0.1-50%。当乙酰水杨酸的量大于80%重量时,它不能保持外用制剂的物理性质。当乙酰水杨酸的量小于0.05%重量时,乙酰水杨酸的止痒活性不足以显示。因此大于80%或小于0.05%重量是不优选的。
可以使用本发明外用制剂的瘙痒疾病的实例是皮肤疾病瘙痒,例如特应性皮炎、湿疹、接触性皮炎、皮脂溢性(seborric)皮炎、荨麻疹、婴儿苔癣(puerile strophulus)、被昆虫螫咬、皮肤瘙痒、瘙痒等;老年性瘙痒;与代谢疾病例如肝硬变、尿毒症、慢性肾炎等有关的瘙痒;与内分泌或内分泌障碍疾病例如糖尿病有关的瘙痒;和与皮肤损伤例如割伤、手术后创伤或灼伤有关的瘙痒。
本发明的外用制剂没有限制,只要它是其中乙酰水杨酸可直接用于皮肤局部表面的制剂,例如软膏、溶液(例如悬浮液、乳液、洗剂)、泥敷剂(cataplasms)、带状制剂(tapes)、气雾剂和外用粉末。
在本发明制剂中可以使用的其他成分是常规外用制剂中使用的任何成分。
对于软膏、乳膏、凝胶和洗剂,可以加入:基质,例如白凡士林(矿脂)、黄凡士林、羊毛脂、纯化蜂蜡、鲸蜡醇、硬脂醇、硬脂酸、氢化油、烃类胶质(hydrocarbon gel)、聚乙二醇、液体石蜡和角鲨烷;溶剂或加溶剂,例如油酸、肉豆蔻酸异丙酯、甘油三异辛酸酯、克罗他米通、癸二酸二乙酯、癸二酸二异丙酯、己二酸二异丙酯、月桂酸己酯(hexyl laulate)、脂肪酸、脂肪酸酯、脂族醇和植物油;抗氧化剂,例如生育酚衍生物、L-抗坏血酸、二丁基羟基甲苯和丁基羟基茴香醚;抗菌剂,例如对羟基苯甲酸盐或酯;润湿剂,例如甘油、丙二醇和透明质酸钠;表面活性剂,例如聚氧乙烯衍生物、甘油脂肪酸酯、蔗糖脂肪酸酯、脱水山梨糖醇脂肪酸酯、丙二醇脂肪酸酯和卵磷脂;增稠剂,例如羧乙烯基聚合物、黄原胶、羧甲基纤维素、羧甲基纤维素钠、羟丙基纤维素和羟丙基甲基纤维素;稳定剂;防腐剂;吸收促进剂和其他合适的填充剂。
对于泥敷剂,可以加入:增粘剂,例如聚丙烯酸和聚丙烯酸共聚物;交联剂,例如硫酸铝、硫酸铝钾、氯化铝、硅铝酸镁(magnesiumaluminometasilicate)和氨基乙酸二羟基铝;增稠剂,例如聚丙烯酸钠、聚乙烯醇、聚乙烯吡咯烷酮、明胶、藻酸钠、羧甲基纤维素、羧甲基纤维素钠、羟丙基纤维素和羟丙基甲基纤维素;多元醇,例如甘油、聚乙二醇(macrogol)、丙二醇和1,3-丁二醇;表面活性剂,例如聚氧乙烯衍生物;香料,例如1-薄荷醇;抗菌剂,例如对羟基苯甲酸盐或酯;净化水和其他合适的填充剂。
对于带状制剂,可以加入:胶粘剂(tacking agent),例如苯乙烯-异戊二烯-苯乙烯(stylene-isoprene-stylene)嵌段共聚物和丙烯酸树脂;增粘树脂,例如脂环族饱和烃类树脂、氢化松香树脂和萜烯树脂;软化剂,例如液体胶和液体石蜡;抗氧化剂,例如二丁基羟基甲苯;多元醇,例如聚乙二醇;吸收促进剂,例如油酸;表面活性剂,例如聚氧乙烯衍生物和其他合适的填充剂。此外,可以在制备含水带状制剂中加入吸水聚合物例如聚丙烯酸钠和聚乙烯醇以及少量净化水。
对于气雾剂,可以加入:基质,例如白凡士林(矿脂)、黄凡士林、羊毛脂、纯化蜂蜡、鲸蜡醇、硬脂醇、硬脂酸、氢化油、烃类胶质、聚乙二醇、液体石蜡和角鲨烷;溶剂或加溶剂,例如油酸、肉豆蔻酸异丙酯、己二酸二异丙酯、癸二酸二异丙酯、甘油三异辛酸酯、克罗他米通、癸二酸二乙酯、月桂酸己酯、脂肪酸、脂肪酸酯、脂族醇和植物油;抗氧化剂,例如生育酚衍生物、L-抗坏血酸、二丁基羟基甲苯和丁基羟基茴香醚;抗菌剂,例如对羟基苯甲酸盐或酯;润湿剂,例如甘油、丙二醇和透明质酸钠;表面活性剂,例如聚氧乙烯衍生物、甘油脂肪酸酯、蔗糖脂肪酸酯、脱水山梨糖醇脂肪酸酯、丙二醇脂肪酸酯和卵磷脂;增稠剂,例如羧乙烯基聚合物、黄原胶、羧甲基纤维素、羧甲基纤维素钠、羟丙基纤维素和羟丙基甲基纤维素,如在软膏、乳膏、凝胶、悬浮液、乳化剂或洗剂中所用的;稳定剂;缓冲剂;甜味剂;悬浮剂;乳化剂;矫味剂;防腐剂;加溶剂和其他合适的填充剂。
对于外用粉末,可以向其中加入填充剂,例如马铃薯淀粉、米淀粉、玉米淀粉、滑石和氧化锌,以及其他合适的添加剂。
按照常规的外用制剂的制备方式,例如通过将每种成分充分捏和(根据需要加入合适的基质),可以制备本发明的外用制剂。
作为活性成分的乙酰水杨酸的量取决于制剂,但是在软膏、乳膏、凝胶和洗剂中的重量为0.05-30%,在泥敷剂中的重量为0.1-20%,在带状制剂中的重量为5-50%,在外用粉末中的重量为10-80%。
根据需要,将如此制备的制剂施用在损伤处。
本发明的最佳实施方式
通过以下实施例和试验例对本发明含乙酰水杨酸的外用制剂进行说明,但是本发明不受这些实施例的限制。实施例1-10(软膏)
按照表1所示的成分,通过在水浴上温热使烃类胶质和溶剂(油酸、Tween80、克罗他米通、己二酸二异丙酯或肉豆蔻酸异丙酯)溶解,并向其中加入乙酰水杨酸(阿司匹林)至溶解或在搅拌下使其完全分散。然后在搅拌下使该混合物冷却,得到软膏。
表1:含阿司匹林的软膏成分
实施例11-15(洗剂)
实施例 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
成分 | 成分比例(重量%) | |||||||||
阿司匹林 | 0.1 | 0.5 | 2.0 | 10.0 | 20.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 |
油酸 | - | - | - | - | - | 5.0 | - | - | - | - |
Tween80 | - | - | - | - | - | - | 5.0 | - | - | - |
克罗他米通 | - | - | - | - | - | - | - | 5.0 | - | - |
己二酸二异丙酯 | - | - | - | - | - | - | - | - | 5.0 | - |
肉豆蔻酸异丙酯 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | - | - | - | - | 5.0 |
烃类胶质 | 97.4 | 97.0 | 95.5 | 87.5 | 77.5 | 93.0 | 93.0 | 93.0 | 93.0 | 93.0 |
按照表2所示的成分,向温热的油层中加入阿司匹林使其溶解或分散。另外将其他成分溶解在预先温热的净化水中,在剧烈搅拌下将油层加至其中。在逐渐冷却下将该混合物混合均匀,得到洗剂。
表2:含阿司匹林的洗剂成分
实施例16-20(凝胶)
实施例 | 11 | 12 | 13 | 14 | 15 |
成分 | 成分比例(重量%) | ||||
阿司匹林 | 0.5 | 2.0 | 10.0 | 5.0 | 5.0 |
克罗他米通 | 1.0 | 2.0 | 5.0 | - | - |
异丙醇 | - | - | - | 2.0 | - |
癸二酸二异丙酯 | - | - | - | - | 5.0 |
角鲨烷 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 |
鲸蜡醇 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 |
脱水山梨糖醇倍半油酸酯 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
聚氧(20)鲸蜡基醚 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 |
丙二醇 | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 |
三乙醇胺 | 0.4 | 0.4 | 0.4 | 0.4 | 0.4 |
净化水 | 85.1 | 82.6 | 71.6 | 79.6 | 76.6 |
按照表3所示的成分,在水浴上使水溶性聚合物溶解后,将阿司匹林溶解或者分散在溶剂中,并将这些成分与其他基质混合均匀,得到凝胶。
表3:含阿司匹林的凝胶成分
实施例21-25(乳膏)
实施例 | 16 | 17 | 18 | 19 | 20 |
成分 | 成分比例(重量%) | ||||
阿司匹林 | 0.1 | 2.0 | 10.0 | 5.0 | 5.0 |
克罗他米通 | 5.0 | 5.0 | 5.0 | 3.0 | |
异丙醇 | - | - | - | 3.0 | 5.0 |
丙二醇 | 45.0 | 45.0 | 45.0 | 45.0 | 45.0 |
聚丙烯酸 | 25.0 | 25.0 | 25.0 | 25.0 | 25.0 |
三乙醇胺 | 0.7 | 0.7 | 0.7 | 0.7 | 0.7 |
净化水 | 24.2 | 22.3 | 14.3 | 18.3 | 19.3 |
按照表4所示的成分,在水浴上使固体基质溶解后,将溶解或者分散在溶剂中的阿司匹林加至其中。将水溶性基质溶解在水中,并将其温热的溶液加至混合物中。将该混合物捏和直至其均匀,得到乳膏。
表4:含阿司匹林的软膏成分
实施例26-30(带状制剂)
实施例 | 21 | 22 | 23 | 24 | 25 |
成分 | 成分比例(重量%) | ||||
阿司匹林 | 0.5 | 2.0 | 10.0 | 2.0 | 2.0 |
克罗他米通 | 2.5 | 2.5 | 2.5 | 5.0 | - |
芝麻油 | - | - | - | - | 5.0 |
癸二酸二异丙酯 | 2.5 | 2.5 | 2.5 | - | - |
鲸蜡醇 | 9.0 | 9.0 | 9.0 | 9.0 | 9.0 |
白凡士林 | 8.0 | 8.0 | 8.0 | 8.0 | 8.0 |
羟基癸醇 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 |
聚乙二醇一硬脂酸酯 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 |
聚氧(9)月桂基醚 | 2.8 | 2.8 | 2.8 | 2.8 | 2.8 |
聚氧(23)鲸蜡基醚 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 |
丙二醇 | 12.0 | 12.0 | 12.0 | 12.0 | 12.0 |
对羟基苯甲酸甲酯 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
对羟基苯甲酸丙酯 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
净化水 | 57.5 | 56.0 | 48.0 | 56.0 | 56.0 |
按照表5所示的成分,向由丙烯酸酯树脂或苯乙烯-异戊二烯-苯乙烯嵌段共聚物组成的胶粘剂(tacking agent)中加入脂环族饱和烃类树脂、液体石蜡、聚丁烯和抗氧化剂等,并在搅拌下将该混合物溶解在有机溶剂例如甲苯等中,或者通过在搅拌下加热使该混合物熔融。向其中加入阿司匹林,并将所得混合物涂布在释放纸上,如果是溶液型,则将所得混合物涂布在释放纸上并干燥。将释放纸层压在柔韧载体上,并切割成所需的大小,得到带状制剂。
表5:含阿司匹林的带状制剂成分
实施例31-33(泥敷剂)
实施例 | 26 | 27 | 28 | 29 | 30 |
成分 | 成分比例(重量%) | ||||
阿司匹林 | 10.0 | 30.0 | 50.0 | 30.0 | 30.0 |
肉豆蔻酸异丙酯 | - | - | - | - | 5.0 |
己二酸二异丙酯 | - | - | - | 5.0 | - |
克罗他米通 | 5.0 | 5.0 | 7.0 | - | - |
丙烯酸酯-乙酸乙烯酯共聚物 | - | - | - | - | 65.0 |
苯乙烯-异戊二烯-苯乙烯嵌段共聚物 | 20.0 | 13.4 | 7.5 | 13.4 | - |
脂环族饱和烃类树脂 | 42.0 | 23.5 | 11.7 | 23.5 | - |
聚丁烯 | 15.0 | 11.6 | 5.6 | 11.6 | - |
液体石蜡 | 7.0 | 15.5 | 17.2 | 15.5 | - |
二丁基羟基甲苯 | 1.0 | 1.0 | 1.0 | 1.0 | - |
按照表6所示的成分,将增粘剂例如聚丙烯酸等和增稠剂在多元醇例如甘油等中加热溶解。冷却后,掺入阿司匹林和其他填充剂至均匀,并向其中加入交联剂,得到粘合凝胶基质。将该凝胶基质涂布在合适的载体例如无纺织物上,切割成所需的大小,得到泥敷剂。
表6:含阿司匹林的泥敷剂成分
实施例34-36(粉末)
实施例 | 31 | 32 | 33 |
成分 | 成分比例(重量%) | ||
阿司匹林 | 0.5 | 2.0 | 10.0 |
聚丙烯酸 | 8.0 | 8.0 | 8.0 |
聚丙烯酸钠 | 4.0 | 4.0 | 4.0 |
羧基纤维素钠 | 5.0 | 5.0 | 5.0 |
酒石酸 | 1.6 | 1.6 | 1.6 |
氨基乙酸二羟基铝 | 0.07 | 0.07 | 0.07 |
甘油 | 34.5 | 33.0 | 25.0 |
克罗他米通 | 2.0 | 2.0 | 2.0 |
芝麻油 | 1.0 | 1.0 | 1.0 |
净化水 | 43.33 | 43.33 | 43.33 |
按照表7所示的成分,将马铃薯淀粉、氧化锌和阿司匹林充分混合,得到粉末。
表7:含阿司匹林的粉末的成分
比较实施例1-2
实施例 | 34 | 35 | 36 |
成分 | 成分比例(重量%) | ||
阿司匹林 | 20.0 | 40.0 | 80.0 |
马铃薯淀粉 | 76.0 | 56.0 | 16.0 |
氧化锌 | 4.0 | 4.0 | 4.0 |
按照软膏的制备方法,制备含表8成分的软膏(比较实施例1-2)。
表8:软膏成分(比较实施例)
比较实施例 | 1 | 2 |
成分 | 成分比例(重量%) | |
苯海拉明 | 1.0 | - |
地塞米松 | - | 0.1 |
丙二醇 | 10.0 | 10.0 |
肉豆蔻酸异丙酯 | 5.0 | 5.0 |
烃类胶质 | 84.0 | 84.9 |
试验[A]:通过施用本发明的外用制剂治疗患者(志愿者)的瘙痒进行止痒活性试验。
根据以下5个步骤的标准评价瘙痒改善的程度:
A:明显有效
B:有效,
C:略微有效,
D:没有变化,
E:恶化。
略微有效(C)或者大于略微有效(A,B)被判定为有效,并计算其有效率。
在下面的试验1-4中,还对含有具有抗组胺活性的苯海拉明的软膏(比较实施例1)和含有地塞米松(类固醇)的比较实施例2的软膏进行评价。
在试验5中,用含有异丙基薁(0.033%)和纯化羊毛脂以及白凡士林作为基质的软膏(以炎性皮炎治疗剂出售的)作为比较实施例。试验1:患者被昆虫螫伤导致的瘙痒的改善
将含有阿司匹林的外用制剂和对照制剂施用在被昆虫螫伤引起瘙痒的每一患者的损伤部位(总共45位志愿者),并评价瘙痒改善的程度。
结果示于表9中。
表9:患者被昆虫螫伤导致的瘙痒的改善程度
组 | 药物(重量%) | 患者数 | 评价 | 有效率(%) | ||||
A | B | C | D | E | ||||
软膏基质 | - | 5 | 0 | 0 | 0 | 4 | 1 | 0 |
实施例1 | 阿司匹林(0.1) | 4 | 0 | 0 | 2 | 2 | 0 | 50.0 |
实施例3 | 阿司匹林(2) | 7 | 2 | 3 | 1 | 0 | 1 | 85.7 |
实施例4 | 阿司匹林(10) | 7 | 1 | 3 | 2 | 1 | 0 | 85.7 |
实施例5 | 阿司匹林(20) | 5 | 2 | 2 | 0 | 1 | 0 | 80.0 |
实施例29 | 阿司匹林(30) | 7 | 2 | 2 | 2 | 1 | 0 | 85.7 |
比较实施例1 | 苯海拉明(1) | 5 | 1 | 0 | 1 | 3 | 0 | 40.0 |
比较实施例2 | 地塞米松(0.1) | 5 | 1 | 1 | 1 | 2 | 0 | 60.0 |
表9的结果清楚地表明,与软膏基质和比较实施例1和2相比,含有阿司匹林的实施例1、3-5和29抑制了由昆虫螫伤导致的瘙痒,并且显示相同或者优越的止痒效果。试验2:患者因湿疹导致的瘙痒的改善
将含有阿司匹林的外用制剂和对照制剂施用在因湿疹引起瘙痒的每一患者的损伤部位(总共32位志愿者),并评价瘙痒改善的程度。
结果示于表10中。
表10:患者因湿疹导致的瘙痒的改善程度
组 | 药物(重量%) | 患者数 | 评价 | 有效率(%) | ||||
A | B | C | D | E | ||||
软膏基质 | - | 3 | 0 | 0 | 0 | 2 | 1 | 0 |
实施例9 | 阿司匹林(2) | 5 | 1 | 1 | 1 | 2 | 0 | 60.0 |
实施例12 | 阿司匹林(2) | 6 | 2 | 1 | 2 | 0 | 1 | 83.3 |
实施例17 | 阿司匹林(2) | 4 | 0 | 1 | 2 | 1 | 0 | 75.0 |
实施例21 | 阿司匹林(0.5) | 4 | 1 | 1 | 1 | 0 | 1 | 75.0 |
实施例33 | 阿司匹林(10) | 3 | 0 | 1 | 1 | 1 | 0 | 66.7 |
比较实施例1 | 苯海拉明(1) | 3 | 0 | 1 | 0 | 2 | 0 | 33.3 |
比较实施例2 | 地塞米松(0.1) | 4 | 1 | 0 | 1 | 2 | 0 | 50.0 |
表10的结果清楚地表明,与软膏基质和比较实施例1和2相比,含有阿司匹林的实施例9、12、17、21和33更多地抑制了因湿疹导致的瘙痒,并且显示优越的止痒效果。试验3:患者因皮肤瘙痒导致的瘙痒的改善
将含有阿司匹林的外用制剂和对照制剂施用在因皮肤瘙痒引起瘙痒的每一患者的损伤部位(总共31位志愿者),并评价瘙痒改善的程度。
结果示于表11中。
表11:患者因皮肤瘙痒导致的瘙痒的改善程度
组 | 药物(重量%) | 患者数 | 评价 | 有效率(%) | ||||
A | B | C | D | E | ||||
软膏基质 | - | 3 | 0 | 0 | 0 | 2 | 1 | 0 |
实施例8 | 阿司匹林(2) | 6 | 0 | 1 | 3 | 1 | 1 | 66.7 |
实施例15 | 阿司匹林(2) | 4 | 1 | 0 | 2 | 1 | 0 | 75.0 |
实施例20 | 阿司匹林(5) | 4 | 0 | 1 | 2 | 1 | 0 | 75.0 |
实施例21 | 阿司匹林(0.5) | 3 | 0 | 0 | 2 | 1 | 0 | 66.7 |
实施例24 | 阿司匹林(5) | 3 | 0 | 1 | 1 | 1 | 0 | 66.7 |
比较实施例1 | 苯海拉明(1) | 4 | 1 | 0 | 1 | 1 | 1 | 50.0 |
比较实施例2 | 地塞米松(0.1) | 4 | 1 | 0 | 1 | 2 | 0 | 50.0 |
表11的结果清楚地表明,与软膏基质和比较实施例1和2相比,含有阿司匹林的实施例8、15、20、21和24更多地抑制了因皮肤瘙痒导致的瘙痒,并且显示优越的止痒效果。试验4:患者因变应性皮炎导致的瘙痒的改善
将含有阿司匹林的外用制剂和对照制剂施用在因变应性皮炎引起瘙痒的每一患者的损伤部位(总共37位志愿者),并评价瘙痒改善的程度。
结果示于表12中。
表12:患者因变应性皮炎导致的瘙痒的改善程度
组 | 药物(重量%) | 患者数 | 评价 | 有效率(%) | ||||
A | B | C | D | E | ||||
软膏基质 | - | 3 | 0 | 0 | 0 | 2 | 1 | 0 |
实施例10 | 阿司匹林(2) | 4 | 0 | 1 | 2 | 1 | 0 | 75.0 |
实施例13 | 阿司匹林(10) | 3 | 0 | 0 | 2 | 0 | 1 | 66.7 |
实施例18 | 阿司匹林(10) | 3 | 0 | 1 | 1 | 1 | 0 | 66.7 |
实施例25 | 阿司匹林(5) | 3 | 0 | 0 | 1 | 0 | 1 | 66.7 |
实施例26 | 阿司匹林(10) | 4 | 1 | 2 | 1 | 1 | 0 | 75.0 |
实施例27 | 阿司匹林(30) | 4 | 0 | 1 | 0 | 2 | 0 | 50.0 |
实施例28 | 阿司匹林(50) | 4 | 1 | 2 | 1 | 1 | 0 | 75.0 |
比较实施例1 | 苯海拉明(1) | 5 | 0 | 1 | 1 | 2 | 1 | 40.0 |
比较实施例2 | 地塞米松(0.1) | 4 | 0 | 2 | 0 | 2 | 0 | 50.0 |
表12的结果清楚地表明,与软膏基质和比较实施例1和2相比,含有阿司匹林的实施例10、13和25-28抑制了因变应性皮炎导致的瘙痒,并且显示相同或者优越的止痒效果。试验5:患者因灼伤导致的瘙痒的改善
将含有阿司匹林的外用制剂和对照制剂施用在每一患者的损伤部位(总共18位志愿者),这些患者是在被灼伤患者中诉说在灼伤的治疗过程中瘙痒的患者。
结果示于表13中。
表13:患者因灼伤导致的瘙痒的改善程度
组 | 药物(重量%) | 患者数 | 评价 | 有效率(%) | ||||
A | B | C | D | E | ||||
软膏基质 | - | 4 | 0 | 0 | 0 | 3 | 1 | 0 |
实施例4 | 阿司匹林(10.0) | 4 | 1 | 1 | 1 | 1 | 0 | 75 |
实施例9 | 阿司匹林(2.0) | 4 | 0 | 2 | 1 | 1 | 0 | 75 |
实施例21 | 阿司匹林(0.5) | 3 | 1 | 1 | 0 | 1 | 0 | 67 |
比较实施例3 | 二甲基异丙基薁(0.033) | 3 | 0 | 0 | 1 | 3 | 0 | 33 |
表13的结果清楚地表明,与软膏基质和比较实施例3相比,含有阿司匹林的实施例4、9和21更多地抑制了在治疗患者灼伤中的瘙痒。
试验[B]:感染疾病的加重作为类固醇的一个副作用经常成为问题。另一方面,皮肤的屏障功能的减小是变应性皮炎的一个成因因素。正如从许多细菌存在于正常皮肤组织中的事实所理解的,当类固醇给患有变应性皮炎的患者施用时,由于致免疫性(immunogenecity)下降,易于引起感染疾病是众所周知的。
因此,使用本发明的实施例2和5以及比较实施例1和2,通过将胸腺和肾上腺重量减少设置为指标,对致免疫性下降进行评价。试验实施例6
在该试验中使用Wistar雄性大鼠(8周龄,6只大鼠/组)。除去背部的毛发后,给大鼠带上颈圈,使其不会舔到背部的试验药物(实施例2、5和比较实施例1、2)。在背部5cm×5cm的区域内涂上试验药物7天(0.5克/大鼠/天)。给药后将大鼠处死,从大鼠上取下胸腺和肾上腺,并测量其重量。
结果示于表14中。
表14:每一制剂给药后胸腺和肾上腺的重量(每体重(100g))
平均值±标准误差
组 | 胸腺重量(mg) | 肾上腺重量(mg) |
未治疗的 | 159±12 | 20.6±1.0 |
软膏基质 | 160±10 | 19.7±1.3 |
实施例2 | 160±7 | 21.0±0.7 |
实施例5 | 162±8 | 20.0±1.3 |
比较实施例1 | 158±9 | 18.7±0.7 |
比较实施例2 | 37±2 | 15.6±1.0 |
如表14所示,与实施例2和5相比,比较实施例2大大减少了胸腺和肾上腺的重量。类固醇软膏减少胸腺和肾上腺的重量,这是致免疫性的一个指标,但是实施例2和5不减少这些器官的重量。因此,与比较实施例2的软膏相比,本发明含阿司匹林软膏的副作用明显小,并且是一种优异的止痒剂。
工业实用性的可能性
本发明治疗瘙痒的外用制剂含有阿司匹林作为活性成分,并且对瘙痒具有优异的治疗效果。此外,本发明治疗瘙痒的外用制剂不减少胸腺和肾上腺的重量,甚至当连续使用时也是如此,因此,本发明制剂属于副作用非常小的药物。本发明可以提供外用制剂,该制剂不仅仅对各种瘙痒具有优异的效果,而且其副作用非常小。
Claims (3)
1.治疗瘙痒的外用制剂,含有乙酰水杨酸作为活性成分。
2.乙酰水杨酸作为活性成分在制备治疗瘙痒的外用制剂中的用途。
3.瘙痒患者的治疗方法,包括对所述患者经皮施用有效量的乙酰水杨酸。
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US (1) | US20030125308A1 (zh) |
EP (1) | EP1249239B1 (zh) |
JP (1) | JP4813725B2 (zh) |
KR (1) | KR20020068385A (zh) |
CN (1) | CN1414856A (zh) |
AT (1) | ATE395920T1 (zh) |
AU (1) | AU779590B2 (zh) |
CA (1) | CA2394471C (zh) |
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HU (1) | HU228233B1 (zh) |
IL (2) | IL150121A0 (zh) |
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NO (1) | NO330872B1 (zh) |
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CN101380317B (zh) * | 2007-09-07 | 2010-12-08 | 英属开曼群岛商安盛开发药物股份有限公司 | 减缓搔痒症的药学组合物 |
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CA2394471C (en) | 2010-05-25 |
ES2304989T3 (es) | 2008-11-01 |
NZ519783A (en) | 2005-05-27 |
KR20020068385A (ko) | 2002-08-27 |
AU1890701A (en) | 2001-07-09 |
IL150121A (en) | 2009-07-20 |
HUP0204208A2 (hu) | 2003-03-28 |
ATE395920T1 (de) | 2008-06-15 |
EP1249239B1 (en) | 2008-05-21 |
CA2394471A1 (en) | 2001-07-05 |
HU228233B1 (en) | 2013-02-28 |
NO20023111D0 (no) | 2002-06-27 |
IL150121A0 (en) | 2002-12-01 |
HUP0204208A3 (en) | 2003-04-28 |
DE60038979D1 (de) | 2008-07-03 |
AU779590B2 (en) | 2005-02-03 |
EP1249239A4 (en) | 2006-04-05 |
NO20023111L (no) | 2002-06-27 |
NO330872B1 (no) | 2011-08-01 |
WO2001047525A1 (fr) | 2001-07-05 |
US20030125308A1 (en) | 2003-07-03 |
EP1249239A1 (en) | 2002-10-16 |
MXPA02006447A (es) | 2003-09-22 |
JP4813725B2 (ja) | 2011-11-09 |
ZA200204624B (en) | 2003-01-22 |
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