CN1112825A - 用抗真菌化合物和卤代抗细菌化合物减少脱发 - Google Patents

用抗真菌化合物和卤代抗细菌化合物减少脱发 Download PDF

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CN1112825A
CN1112825A CN95104671A CN95104671A CN1112825A CN 1112825 A CN1112825 A CN 1112825A CN 95104671 A CN95104671 A CN 95104671A CN 95104671 A CN95104671 A CN 95104671A CN 1112825 A CN1112825 A CN 1112825A
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D·圣莱泽
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Abstract

本发明涉及将至少一种抗真菌剂和不属于大环 内酯和吡喃糖苷系列的至少一种卤代抗细菌剂用于 化妆组合物或用于制备皮肤用组合物，这些组合物可 用于治疗脱发。

Description

本发明涉及将至少一种抗真菌剂和不属于大环内酯和吡喃糖苷系列的至少一种卤代抗细菌剂用于化妆组合物或用于制备皮肤或皮肤病用组合物，这些组合物可用于治疗脱发。
长期以来，本技术领域的普通技术人员已知人类自然脱发反映出交替生长相（les        phases）（phase        anagene）和脱发相（phase        telogene）之间毛囊的总体平衡状态。在phase        anagene中的毛囊数与在phase        telogene中的毛囊数之平均比值为9（90/10）左右。其它相（phase        catagene）中毛囊百分比似乎很低。
在正常生理状态下，自然脱发可估计为平均几百根毛发/天。而在有病的生理状态下，该值可达到数百根/天，因而导致脱发。
但是，头皮表面存在微生物区系，当然是由细菌和酵母组成的。在该区系的天然组成不平衡时，脱发就会增加。
而且，已知某些因素如激素不平衡，生理应激或食物不足会加速这种现象。
为了减少脱发，FR2，618，068专利已提出应用含有抗真菌剂的组合物，其中抗真菌剂任选可与抗炎剂和/或与选自大环内酯或吡喃糖苷系列的抗菌素组合。但是，这些组合物并不完全令人满意，其中虽然减少脱发的效果比单独用抗真菌剂的效果要明显得多，但是应用抗炎剂并不是没有缺点。的确，这些抗炎剂有可能改变微生物区系的天然组成，从而加大了受感染的危险。
抗菌剂也不是完全令人满意，因为这些制剂在化妆或皮肤用组合物中常常不稳定。另外，应用这些细菌时会出现细菌抗药性或耐药性现象，因而会使组合物意欲减少脱发的效果降低。
应用抗细菌剂并不会出现这些耐药性现象，但大多数常用抗细菌剂似乎会阻止抗真菌剂发挥作用，因此也降低了含这两种制剂的组合物效果。
因此，申请人已寻求解决这一问题的办法。现已发现含有抗真菌剂并意欲使脱发减缓的组合物在使该制剂与不属于大环内酯和吡喃糖苷系列的卤代抗细菌剂组合时效果更好。出人意料的是这些卤代抗细菌剂似乎不会阻止抗真菌剂发挥作用，而在用其它非卤代抗细菌剂时就会出现这种阻止作用。
另外，这些卤代抗细菌剂在加入本发明组合物之后特别稳定并且不会使细菌出现耐药性。
因而，本发明涉及将至少一种抗真菌剂和不属于大环内酯和吡喃糖苷系列的至少一种卤代抗细菌剂用于化妆组合物或用于制备皮肤或皮肤病用组合物，这些组合物可用于治疗脱发。
此外，也发现经过几个星期的治疗后，毛发再生得以改善并且毛发尤其显得光亮而不觉油腻。
根据本发明，所谓抗真菌剂指的是可阻止或防止酵母，尤其是在富含皮脂腺的表皮表面上，特别是头皮表面上发现的酵母，例如Pityrosporurm        ovale及其变种（Pityrosporum        orbiculare和Malassezia        furfur）生长的任何物质。
在本发明所用抗真菌剂中，尤其是可举出terbinafine，zincpirythione，硫化砷，焦油及其衍生物，十一碳烯酸及其盐以及羟基吡啶酮衍生物如CICLOPIROX：6-环已基-1-羟基-4-甲基-2-（1H）-吡啶酮，或OCTOPIROX：1-羟基-4-甲基-6-（2，4，4-三甲基戊基）-2-（1H）-吡啶酮。
这些抗真菌剂在本发明组合物中的浓度优选为组合物总重量的0.01-5wt%（重量百分比），更优选为0.1-2wt%。
根据本发明，所谓卤代抗细菌剂指的是含有至少一个卤原子并且可阻止或防治富含皮脂腺的表皮表面上存在的细菌区系生长的任何物质。
本发明所用卤代抗细菌剂优选为苯衍生物。
在本发明所用卤代抗细菌剂中，尤其可举出氯代抗细菌剂如CIBA-GEIGY公司以商品IRGASAN销售的Triclosan，也就是5-氯-2-（2，4-二氯苯氧基）苯酚，洗必太及其衍生物，氯霉素及BAYER公司以商品CLIMBAZOLE销售的1-（4-氧苯氧基）-1-（1H-咪唑基）-3，3-二甲基-2-丁酮。这些卤代抗细菌剂在本发明组合物中的浓度优选为组合物总重量的大致0.01-10wt%，更优选为0.1-2wt%。
抗真菌剂与卤代抗细菌剂之重量比范围很宽，优选可为0.2-10。
本发明组合物可以常用的各种形式用于化妆品或在皮肤病领域用于治疗或处理头皮。
这些组合物尤其可呈洗液，洗发水，泡沫，乳液，凝胶，棒，喷雾剂，油膏，粉，固体或液体皂的形式。
生理上可接受的介质通常包括水或水与至少一种有机溶剂的混合物，其中该溶剂局部应用时是生理上可接受的。在这些溶剂中，可举出丙酮，C1-C4低级醇如乙醇和异丙醇，烷二醇如乙二醇和丙二醇，乙二醇单甲醚、甲***或单丁醚，丙二醇和二丙二醇单***，短链酸的C1-C4烷基酯和聚四氢呋喃醚。在存在这些溶剂时，其浓度优选为组合物总重量的1-80wt%。
介质可用常用于化妆品或医药的增稠剂增稠。
在这些增稠剂中，尤其可举出纤维素及其衍生物如纤维素醚，异生物形成多糖化合物如合成生物聚合胶，scleroglucanes以及可交联或未交联的聚丙烯酸。
增稠剂浓度优选为组合物总重量的大致0.1-5wt%。
根据组合物所要求的各种实施方案，本技术领域的普通技术人员应知道选择常用于制造这类组合物的必要化合物和助剂。
在这些助剂中，尤其可举出防腐剂，稳定剂，pH调节剂，渗透压改进剂，乳化剂，滤光剂，抗氧化剂，香料，染料，阴离子、阳离子、非离子、两性或两性离子表面活性剂或其混合物，聚合物等。
除构成本发明主题的特定组合外，这些组合物也可包括已知可减少脱发的化合物。
本发明另一目的是将毛发和/或头皮进行化妆处理以减少脱发的方法，其中在毛发和/或头皮上涂抹上述组合物。
这种涂抹的优选实施方式是在头皮的全部或部分上涂1-20g组合物，其中每天涂抹1-2次，每星期涂抹1-7天，涂抹时间为1-6个月。
以下实施例旨在说明本发明，但并不限制本发明范围。
实施例1
制成下列组成的洗发水：
含2.2mol环氧乙烷的月桂基醚硫酸钠        12g
椰子单异丙醇酰胺        3.5g
以三乙醇胺季铵化的羟基纤维素        0.4g
HOECHST公司以商名OCTOPIROX销售的1-
羟基-4-甲基-6-（2，4，4-三甲基戊基）-2-（1H）
-吡啶酮        0.3g
CIBA-GEIGY公司以商名IRGASAN
销售的Triclosan        0.25g
防腐剂        0.3g
香料        0.4g
水        qsp（适量至）        100g
每星期定期应用2-3次时，该洗发水可减少脱发，而同时又可改善头发的总体外观效果。
实施例2
制成如下组成的头皮洗液：
乙醇        38g
蓖麻油        0.2g
ICI公司销售的葡糖酸洗必太        0.4g
十一碳烯酸        0.25g
香料        0.3g
染料        0.05g
水qsp        100g
每天在头皮和头发上涂抹该制品并且不进行冲洗，该洗液可减少脱发，同时又可改善头发的总体外观效果。
实施例3
制成下列组成的头发泡沫：
MERCK公司以商名MERQUAT100销售的二烯丙基二甲基氯化铵聚合物        1.5g
NATIONAL        STARCH    公司以商名CELQUAT    LOR销售的羟乙基纤维素和二烯丙基二甲基氯化铵的共聚物            0.3g
AKZO公司以商名ARQUAD-16-25W
销售的季铵盐        0.3g
DOW        CORNING公司以商名QC        F2-1671销售的硅胶        0.1g
丙二醇        5g
苯氧基乙醇        0.4g
HOECHST公司以商名OCTOPIROX销售的1-羟基
-4-甲基-6-（2，4，4-三甲基戊基）-2-（1H）
-吡啶酮        0.2g
氯霉素        0.3g
水qsp        100g
推进剂：烃（异丁烷/丁烷/丙烷的55/23/22混合物）
定期涂抹该泡沫后，已发现减少了脱发并且改善了头发的总体外观。
实施例4
制成下列组成的头皮喷雾剂：
异链烷烃（HULS公司销售的异丁烷）        0.5g
DOW        CORNING公司以商名DC        200FLUID
销售的聚二甲基硅氧烷        1.2g
DOW        CORNING公司以商名DC929EMULSION销售的聚氨基硅氧烷        0.4g
乙醇        15g
GOODRICH公司以商名CARBOPOL980销售的
交联丙烯酸聚合物        0.1g
CIBA-GEIGY公司以商名IRGASAN销售的
Triclosan        0.35g
HOECHST公司以商品OCTOPIROX销售的1-羟基
-4-甲基-6-（2，4，4-三甲基戊基）-2-（1H）
-啶吡酮        0.1g
十一碳烯酸        0.15g
三乙醇胺        qs        pH7
水        qsp        100g
该组合物包装在喷雾瓶中。
定期喷涂该喷雾剂后，已观察到减少了脱发并且改善了头发的总体外观效果。
实施例5
制成下列组成的防治脱发的洗液：
BAYER公司以商名CLIMBAZOLE销售的1-（4-氯苯氧基）-1-（1H-咪唑基）-3，3-二甲基-2-丁酮        0.1g
十一碳烯酸        0.15g
乙醇        38g
香料        qs
染料        qs
水        qsp        100g
每天涂抹到头发上并且不进行冲洗，结果该洗液可减少脱发并且同时改善头发的总体外观效果。
实施例6
效果试验
制成以下洗液以试验本发明组合物的效果：
HOECHST公司以商名OCTOPIROX销售的1-羟基-4-
甲基-6-（2，4，4-三甲基戊基）-2-（1H）-吡啶酮        0.25g
CIBA-GEIGY公司商名IRGASAN销售的Trichosan        0.3g
乙醇        45g
香料        qs
水        qsp        100g
20位显示雄激素性脱发的男性应用该洗液。这些人每天一次将该组合物涂在头发上并且不进行冲洗，时间为9个月。在这段试验期间，定期给每个人发放标准调查表。
所得结果列在下表中。
A）头发外观
这些人自述其头发的油性，光泽，粘性或正常性质。
结果亦列在下表中。
Figure 951046713_IMG1
已观察到大多数人员从开始的几个星期就注意到其头发状态的全面正常化，尤其是就其油性，光泽和粘性外观而言。
B）皮脂溢的变化
这些人员评价了其皮脂溢变化，可能是增加，稳定或减少，其结列在下表中。
Figure 951046713_IMG2
对少数人员而言，已观察到在皮脂溢增加的过渡期之后皮脂溢又变得正常。未发现反应性皮脂溢。
C）观察瘙痒
这些人员报告了存在或不存在瘙痒的情况，结果列下表中。
已观察到从开始的几个星期就达到很明显的改善。
D）观察脱发
由这些人员估计脱发。在每次调查时，向这些人员出示含有与其头发颜色类似并且数量从约10-约150根不等的头发的信封。然后由每一人员指明与其洗发期间脱发估计值最相应的信封。
结果表明在涂抹期间脱发量增加，稳定或减少的情形。
下表列出这些结果：
Figure 951046713_IMG4
涂抹该组合物达几星期后观察到脱发明显减少。涂抹5-6个月后这种减少的效果倾于稳定。

Claims (16)

1、将至少一种抗真菌剂和不属于大环内酯和吡喃糖苷系列的至少一种卤代抗细菌剂用于化妆组合物或用于制备皮肤用组合物，这些组合物可用于治疗脱发。
2、权利要求1的用途，其特征在于抗真菌剂选自可阻止或防治富含皮脂腺的表皮表面上存在的酵母生长的物质。
3、权利要求1或2中任一项的用途，其特征在于抗真菌剂选自下列化合物：terbinafine，zinc        pirythione，硫化砷，焦油及其衍生物，十一碳烯酸及其盐以及羟其吡啶酮衍生物。
4、权利要求3的用途，其特征在于羟基吡啶酮衍生物选自6-环已基-1-羟基-4-甲基-2-（1H）-吡啶酮和1-羟基-4-甲基-6-（2，4，4-三甲基戊基）-2-（1H）-吡啶酮。
5、权利要求1-4中任一项的用途，其特征在于卤代抗细菌剂选自含有至少一个卤原子并且可阻止或防治富含皮脂腺的表皮面上存在的细菌区系生长的物质。
6、权利要求5的用途，其特征在于卤代抗细菌剂为苯衍生物。
7、权利要求5或6中任一项的用途，其特征在于卤代抗细菌剂为氯代抗细菌剂。
8、权利要求7的用途，其特征在于氯代抗细菌剂选自下列化合物：5-氯-2-（2，4-二氯苯氧基）苯酚，洗必太及其衍生物，氯霉素和1-（4-氯苯氧基）-1-（1H-咪唑基）-3，3-二甲基-2-丁酮。
9、权利要求1-8中任一项的用途，其特征在于抗真菌剂浓度为组合物总重量的0.01-5wt%。
10、权利要求9的用途，其特征在于抗真菌剂浓度为组合物总重量的0.1-2wt%。
11、权利要求1-10中任一项的用途，其特征在于卤代抗细菌剂的浓度为组合物总重量的0.01-10wt%。
12、权利要求11的用途，其特征在于卤代抗细菌剂浓度为组合物总重量的0.1-2wt%。
13、权利要求1-12中任一项的用途，其特征在于抗真菌剂与卤代抗细菌剂之重量比为0.2-10。
14、权利要求1-13中任一项的用途，其特征在于组合物可呈洗液，洗发水，泡沫，乳液，凝胶，棒，喷雾剂，油膏，粉，固体或液体皂的形式。
15、权利要求1-14中任一项的用途，其特征在于组合物含有至少一种助剂，选自增稠剂，防腐剂，稳定剂，pH调节剂，渗透压改进剂，乳化剂，滤光剂，抗氧化剂，香料，染料，聚合物，表面活性剂及用于局部涂抹的任何其它助剂。
16、头发和/或头皮化妆处理方法，其特征在于涂抹上述权利要求中任一项的化妆组合物以减少脱发。
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