CN1691931A - 具有天然成分的局部组合物及其使用方法 - Google Patents
具有天然成分的局部组合物及其使用方法 Download PDFInfo
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- CN1691931A CN1691931A CNA2003801002786A CN200380100278A CN1691931A CN 1691931 A CN1691931 A CN 1691931A CN A2003801002786 A CNA2003801002786 A CN A2003801002786A CN 200380100278 A CN200380100278 A CN 200380100278A CN 1691931 A CN1691931 A CN 1691931A
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Abstract
本发明公开了减轻皮肤刺激症状或病症的具有至少一种有效抑制COX-2酶、NGF蛋白和/或TNF-α蛋白活性的植物提取物的局部组合物。优选地,该组合物具有美容上、皮肤学上或药学上可接受的载体。除了抑制酶的植物材料和可接受的载体之外,组合物还具有至少一种已知产生皮肤刺激的活性成分。本发明还公开了皮肤刺激病症或症状的治疗方法,包括局部施用本发明的组合物。还公开的是组合物和组合物对皮肤局部给药的方法,以改善皮肤美学外观和/或提供皮肤抗老化优点。
Description
相关申请
这是2002年12月26日提交的共同未决的美国专利申请序列号10/330,040的连续部分申请,且要求美国专利申请序列号10/330,040的优先权和权益。
背景技术
1.发明领域
本发明涉及具有源自植物或植物材料的活性成分的局部组合物。更具体地,本发明涉及改善皮肤外观的局部组合物(topicalcomposition),尤其通过借助具有至少一种抑制COX-2酶、NGF蛋白和/或TNF-α蛋白活性的天然植物提取物的局部组合物,减轻皮肤刺激。还更具体地,本发明涉及使用本发明的局部组合物的方法。
2.相关技术说明
在适于多种医药、治疗和美容目的的局部组合物中,已经采用了源于植物的天然成分。这种活性物质能够得自植物的各种部分,例如种子、叶、根、皮、花、球果、茎、根茎、愈伤组织细胞(callus cells)、原生质体、器官和器官系统,以及分生组织。活性成分以多种形式掺入这种组合物。这些形式包括纯的或半纯的组分,固体或液体提取物或衍生物,或者固体植物物质。植物物质可被切碎、磨碎、压碎或别的方式物理修正以便掺入组合物。
采用源于植物或植物部分的活性成分时通常遇到的问题是它们天然存在的浓度相对较低。这样低的浓度常常需要加工较大数量的植物叶子/组织或种子以便获得所需的或有效数量的活性成分。对于珍稀植物或植物部分,这样大的数量是不可得到的或难于获得的。
目前,多种局部施用的药物和美容产品是商业用途。例如,在美容品工业发展可以局部施用至皮肤,能够提供抗老化、水合、和/或皮肤质地优点的产品中具有现代活跃的兴趣。增强皮肤外观的美容产品需求日益增长。消费者兴趣在于缓和或延迟按照年龄、激素和/或光老化皮肤迹象,例如细纹、皱纹、干燥皮肤和皮肤下垂。老化过程期间,皮肤的肤色,即皮肤的颜色和外观,由于内部老化和/或暴露于阳光缓慢恶化。美容手术可用于治疗老化皮肤,但是这种治疗价格昂贵,并且带有通常与麻醉和手术相关的风险。选择性地,能够提供抗老化或其它皮肤护理优点的美容产品是消费者极度期望的。然而,伴随药用和美容用局部施用产品的一个问题是活性成分常常刺激皮肤。这种副作用可能限制某一美容品或药物活性成分的使用或浓度。
美容皮肤护理产品的数量稳步上升。通常地,这类产品含有有机酸或其它作为活性成分的材料。这类活性成分包括,例如,羟基化酸和它们的衍生物,例如ω-羟基酸(即十一酸)、α-羟基酸(即乳酸、羟基乙酸(glycolic)、柠檬酸),β-羟基酸(即水杨酸、5-n-辛酰基水杨酸),和类维生素A(即视黄酸、视黄醇)。已知这些活性成分的明显的缺点是它们常常与消费者的皮肤刺激或不适有关,其特征在于施用后有灼伤、刺痛、痒或紧绷感。在美容品工业和药物工业对于含有各种有效且不产生不希望的皮肤刺激副作用的活性成分的局部施用产品有广泛需要。已知使用局部施用产品时,显著数量消费者具有过敏性皮肤或对过敏性皮肤反应敏感。例如,具有某些表面活性剂、防腐剂、香料等等,以及活性成分的产品,具有皮肤刺激性特征。
更具体地,考虑到先前美容品工业中需求和限制的讨论,对局部施用的、美容品组合物存在需要,这种组合物采用天然成分作为活性组分,具有无皮肤刺激副作用的皮肤优点。
过敏性皮肤或皮肤炎症治疗的方法是公知的。例如,美国专利No5,993,833涉及治疗敏感皮肤的方法,其包括服用具有拮抗剂化合物的组合物。美国专利NO6,143,303涉及含有植物Dodonaea petiolaris和车桑子(dodonaea viscosa)提取物的抗炎、镇痛组合物。
除了向皮肤局部施用市场上各种药用和美容产品,还需要有效局部施用组合物,该组合物掺有天然植物提取物或合成形式的天然植物提取物,以改善皮肤的美学外观,尤其发炎的皮肤,或者通过缓和或消除由使用这类活性物质引起的刺激性副作用达到包含于该组合物内的活性成分的优点。
发明概述
本发明的一项目的是提供美容品组合物,其改善皮肤外观,包括补救老化影响。
本发明的另一项目的是提供局部美容品或药物组合物,它在药学上或美容上可接受的载体中,具有植物来源的皮肤抗刺激物活性成分或植物来源的皮肤抗刺激物活性成分的掺混物。
本发明的又一项目的是提供释放源于植物提取物的皮肤抗刺激物活性成分和有效浓度的美容、皮肤学或药物活性成分的局部组合物。
本发明的还一项目的是提供具有抑制COX-2酶、NGF蛋白和/或TNF-α蛋白的植物提取物的局部组合物。
本发明进一步的目的是提供局部施用这类组合物的方法。
本发明还进一步的目的是提供改善皮肤外观的方法,包括补救老化影响,并且也提供通过局部施用本发明的组合物治疗皮肤刺激症状或病症。
本发明的这些和其它的目的和优点,及其等价物,通过具有植物提取物或植物提取物掺混物的抗刺激美容和药物组合物,以及使用这类适于局部施用的组合物获得。
本发明提供用于治疗皮肤以改善皮肤美学外观和/或对皮肤提供抗老化优点的局部组合物。同样提供的是用于治疗皮肤的局部组合物,这种治疗对皮肤产生减弱的刺激作用,优选无可见的刺激作用。
本发明还提供用于治疗皮肤刺激症状或用于治疗引起皮肤刺激性反应的皮肤病症的局部组合物。这些组合物具有美容上、皮肤学上,或药学上有效量的至少一种足够抑制COX-2酶、NGF蛋白和/或TNF-α蛋白的植物提取物,和美容上、皮肤学上,或药学上可接受的载体。
本发明的组合物具有至少一种植物提取物。至少一种植物提取物是以下任何种:冬青(Ilex purpurea Hassk)、川芎(Ligusticumchiangxiong)、日本山茶(Asmunda japonica)、女贞子(Ligusticumlucidum)、胶虫树(Butea frondosa)、或香榄(Mimusops elengi)。优选地至少一种植物提取物是以下任何种:冬青、川芎、日本山茶、胶虫树、或女贞子。
本组合物减轻刺激症状或病症,这些症状包括但不限于:红斑、牛皮癣、水肿、痤疮、疣、色素沉着过度、色素沉着不足、轮(wheeling)、斑点(blotchiness)、肤色不均、鳞屑(scaling)、鳞片(flaking)、痒、灼伤、蜇伤(stinging)、麻刺感、麻木、风刺激、温度刺激、烟刺激,和化学刺激。
本发明详细描述
本发明提供具有植物提取物或植物提取物掺混物的局部组合物,优选天然植物提取物,它能够减轻皮肤刺激,包括唇部,尤其由美容、皮肤学或药物产品中活性成分引起的刺激。本发明的组合物对各种皮肤刺激症状或病症具有优点。
本发明还提供组合物以改善皮肤美学外观,包括补救老化影响。这些优点通过下列的一种或多种表示:孔径大小的减小;肤色、光泽(radiance)、透明度和/或紧固度(tautnes)的改善;促进抗氧化剂活性;皮肤坚实度(firmness)、丰满度(plumpness)、柔韧度(suppleness)和/或软度(softness)的改善;前胶原和/或胶原生成的改善;皮肤质地改善和/或促进皮肤抗纹理化(retexturization);皮肤障碍修复和/或功能的改善;皮肤轮廓外观改善;皮肤光泽(luster)和/或光亮度(brightness)复原;皮肤内由于老化和/或绝经减少的基本营养物和/或组分的补充;皮肤细胞中联系的改善;细胞增生和/或增殖的增加;由于老化和/或绝经减少的皮肤细胞代谢增加;皮肤增加水分的改善;细胞更新的促进和/或加速;皮肤厚度增加;皮肤敏感性减小;皮肤弹性和/或回弹的增加;脱落的增加,借助或未借助α或β羟基酸、酮酸或其它剥离剂(exfoliant)。从而,本发明的方法以组合物重量计,提供约0.0001wt%至约20wt%的有效量,其在以下一种或多种治疗中有效:减少或防止胶原丧失;改善皮肤坚实度/丰满度;改善皮肤质地;减少/预防纹(line)和皱纹(wrinkle);改善肤色;增加皮肤厚度;减小孔径;减少皮肤脱色;减少痤疮;减少牛皮癣;减少皮肤敏感性;和减少疣。
本发明还提供具有抗老化优点的组合物。该组合物具有有效量的一种或多种成分,当施用至人皮肤时,它预防、治疗和/或改善在其施用的皮肤区域或部分的老化体征。具体而言本发明提供治疗皮肤以预防、抑制、减少和/或改善皮肤学老化体征的组合物和方法,这些体征归因于,例如年龄老化、激素老化,和/或光老化。这种老化体征包括,但不限于皮肤脆性;胶原和/或弹性蛋白损失;皮肤雌激素失衡;皮肤萎缩;纹和/或皱纹的外观和/或深度,包括细纹;皮肤脱色,包括黑眼圈;皮肤下垂;皮肤疲劳和/或紧张,例如,归因于外界影响的皮肤开裂(break out),例如污染和/或温度变化;皮肤干燥;皮肤鳞片;细胞老化;肤色、弹性和/或光泽损失;皮肤坚实度损失;差的皮肤质地;皮肤弹性和/或回弹力损失;和薄皮。
为改善皮肤的美学外观,这些组合物具有至少一种本发明的天然植物提取物或合成形式的天然植物提取物;即冬青、川芎、日本山茶、女贞子、胶虫树、或香榄。优选地至少一种植物提取物是以下任何种:冬青、川芎、日本山茶、或女贞子。同样优选地,这些组合物还具有一种或多种美容领域公知的美容学活性剂,包括但不限于本文列举的美容剂,它们具有一种或多种以上确定的皮肤外观优点。
皮肤刺激可由多种物理或化学因素引起,包括环境因素,例如暴露于风、热或寒冷、空气污染物或卷烟烟雾。美容和药物产品具有产生作为副作用的可视皮肤刺激的组分或各组分的组合。对皮肤刺激敏感有个体差异,经常限制某些产品的用途或活性成分浓度的使用,这些活性成分会在较高浓度产生多种有益结果,但是产生刺激皮肤的副作用。皮肤刺激症状或病症包括,但不限于,红斑、牛皮癣、水肿、色素沉着过度、色素沉着不足、痤疮、疣、轮、斑点、肤色不均、鳞屑、鳞片、痒或瘙痒、紧绷感、灼伤、刺痛、蜇伤、麻刺感、麻木、风刺激、温度刺激、烟刺激,化学刺激,或其任意结合。
美容、皮肤学或药物产品通常具有产生皮肤刺激的活性剂或药剂。具有皮肤刺激作为副作用的活性剂的例子包括但不限于,羟基酸和它们的衍生物,α-羟基酸(即乳酸、羟基乙酸、柠檬酸、苹果酸、酒石酸、苯乙醇酸、葡糖酸、甲基乳酸、苯基乳酸、阿卓乳酸、甘油酸、二苯乙醇酸、z-羟基庚酸、z-羟基辛酸,及其任意结合),β-羟基酸(即水杨酸、5-n-辛酰基水杨酸和其它的水杨酸衍生物),类维生素A(即视黄酸及其衍生物;视黄醇和其酯);蒽林(即二氧蒽酚)、蒽素(anthranoids)、过氧化物(即过氧化苯甲酰)、长压定、锂盐、代谢拮抗剂、维生素D及其衍生物、毛发染料或色素(即对-苯二胺及其衍生物;氨基酚)、醇类加香溶液(即香水;花露水;须后水;除臭剂)、止汗剂(即一些铝盐)、脱毛(depilatory)或毛发持久活性剂(即硫醇)、脱色素剂(即氢醌),和一些杀虫活性剂。如果局部产品具有抗刺激保护,在产品中增加正常刺激活性剂(即AHA或SHA)的量,同时不产生使人不愉快的皮肤刺激或刺激副作用是可能的。本组合物的使用使得可以与该活性剂通常使用的数量或浓度相比,通过增加美容、皮肤学或药物活性剂的浓度或数量来改善美容、皮肤学或药物产品的功效。
现在已经发现,将拮抗肿瘤坏死因子α(TNF-α)蛋白、神经生长因子(NGF)蛋白和/或环加氧酶-2(COX-2)酶的植物提取物添加至局部美容、皮肤学或药物组合物,优选具有皮肤刺激组分的组合物,可减轻或甚至消除皮肤刺激。
已知有两种不同的环加氧酶(COX)酶同种型,即COX-1和COX-2。COX-1以恒定水平存在于人体几乎所有部位,并包含于胃前列腺素的生成中,维持正常的肾功能,并预防血小板聚集。相反,人体通常不含COX-2,其与炎症相关原位诱发。诱发之后,COX-2产生大量的前列腺素,特征性地引起疼痛、发烧和周围血管舒张引起的局部充血和形成水肿。COX-2的选择性抑制会有益于减轻炎症和相关的疼痛,而不会干扰正常的人体机能。
TNF-α,与其它化合物,例如,举例来说,组胺或白细胞介素,是炎症介质。在美容、皮肤学或药物局部产品中使用TNF-α的一种或多种抑制剂或拮抗剂的会减轻皮肤炎症。
NGF是良好表征的神经营养蛋白族成员,它在神经系统内分泌,还包括在皮肤内分泌。它已知会引起炎症痛觉过敏,并且在包括特应性皮炎的各种皮肤病症中增加。NGF还已知可活化肥大细胞并调节促炎神经肽,例如物质P。NGF的抑制会减轻皮肤炎症和与炎症相关的痛觉过敏。
本发明提供具有至少一种其含量可有效抑制TNF-α蛋白、NGF蛋白和/或COX-2酶的植物提取物的组合物。
本发明在其最广的考虑内包括在任何局部美容品、皮肤学或药物组合物中,使用任何适当的植物提取物或成分抑制TNF-α蛋白、NGF蛋白和/或COX-2酶以减轻或治疗可见或主观皮肤刺激。术语“皮肤刺激”包括,但不限于,皮肤可见的和/或主观刺激,其包括但不限于红斑、牛皮癣、水肿、色素沉着过度、色素沉着不足、痤疮、疣、轮、斑点、肤色不均、鳞屑、鳞片、痒、灼伤、蜇伤、麻刺感、麻木、风刺激、温度刺激、烟刺激,和/或化学刺激。本发明的组合物在治疗临床症状不明显的刺激中也是有效的,即无充血存在时,但是此处皮肤在细胞水平已经受到威胁。
在本发明的组合物中用来抑制COX-2酶、NGF蛋白和/或TNF-α蛋白以治疗皮肤过敏的一种或多种植物成分,优选天然提取物,包括一种或多种提取物,或天然成分。这些提取物或天然成分优选是以下的任意一种或多种:冬青、川芎、日本山茶、女贞子(Ligusticum licidum)、胶虫树,或香榄。更优选这些植物成分,优选提取物,是以下的一种或多种:冬青、川芎、日本山茶、胶虫树、或女贞子。前述提取物典型地通过亲水或疏水提取所述植物或其部位得到。特别优选地是川芎和胶虫树的结合。
本组合物内植物提取物的含量约是0.0001重量百分比(wt%)至约99wt%,优选约0.001wt%至约20wt%,以组合物的总重量计。植物提取物的含量更优选约0.01wt%至约5wt%,还更优选约0.1wt%至约3wt%,以组合物的总重量计。
本发明提供,作为一项实施方案,用于皮肤刺激治疗的组合物,它具有美容上、皮肤学上或药学上有效量的、足以抑制COX-2酶、NGF蛋白和/或TNF-α蛋白的至少一种源自以上植物来源的提取物。优选地,这些组合物还具有美容上、皮肤学上或药学上可接受的载体。此外,可方便地采用这些提取物的掺混物。可方便地采用本发明的实施方案以治疗各种皮肤刺激症状或病症(即红斑、牛皮癣、水肿、色素沉着过度、色素沉着不足、痤疮、疣、轮、斑点、肤色不均、鳞屑、鳞片、痒、灼伤、蜇伤、麻刺感、麻木、风刺激、温度刺激、烟刺激,和/或化学刺激)。
在本发明的其它实施方案中,组合物可具有活性成分,或活性成分的结合,其含量通常会产生皮肤刺激症状或病症,如果没有在这些组合物中掺入美容上、皮肤学或药学上有效量的、足以抑制COX-2酶、NGF蛋白和/或TNF-α蛋白的一种或多种源自以上植物来源的提取物。这些提取物或提取物的掺混物,和通常会产生皮肤刺激症状或病症量的一种或多种活性成分或活性成分的结合物,以适于局部施用的形式方便地掺入药学上或美容上可接受的载体。
可用于本发明局部组合物的美容上、皮肤学或药学上可接受的载体包括,但不限于,一种或多种含水系统,甘油,C1-4醇,脂肪醇,脂肪族醚、脂肪族酯,多元醇,二元醇,植物油,矿物油,脂质体,层状类脂材料,硅酮油,水或它们的任意结合。
此外,本发明组合物的载体可以是均相制剂或乳剂的形式。这些乳剂包括,但不限于,水包油,油包水,硅氧烷包水,和多相,包括三相乳剂。这些乳剂可覆盖宽范围的稠度,包括稀润肤液(lotion)(它还适于喷雾或气溶胶给药),乳脂状润肤液,淡霜和浓霜。其它适合的局部载体包括无水液体溶剂,例如油和醇;水基单相液体溶剂(例如含水-醇性溶剂体系);无水固体和半固体(例如凝胶和膏棒(stick));和水基凝胶和摩丝(mousse)体系。可用于本发明的载体或载体体系的例子在以下四篇参考文献中描述了,它们所有在此引入作为参考:“Sun Products Formulary(防晒产品一览表)”,Cosmetics & Toiletrics,vol.105,pp.122-139(1990年12月),“Sun Products Formulary(防晒产品一览表)”,Cosmetics & Toiletrics,vol.102,pp.117-136(1997年3月);Figueroa等的美国专利No.4,960,764,1990年10月2日出版;和Fukuda等的美国专利No.4,254,105,1981年3月3日出版。
本发明的局部组合物可配制成任何适当的产品形式。这些产品形式包括但不限于,气溶胶喷雾剂,霜,乳剂,固体,液体,分散剂,泡沫,凝胶,润肤液,摩丝,软膏,散剂,贴片(patch),香膏剂(pomade),溶液,泵送喷雾剂,膏棒,和小毛巾。产品应用包括全部局部皮肤护理产品制剂,彩色美容品,个人护理产品(即止汗剂(anti-perspirant),除臭剂等),毛发护理产品,和局部药品。本发明的组合物适用于或用作美容上的、皮肤学或药物局部应用产品,其可通过本领域公知的种种方法方便的制备。
本发明局部组合物可包括以下的一种或多种:麻醉剂、抗变应原剂、抗真菌剂、抗微生物剂、其它抗炎剂、抗氧化剂、抗菌剂、螯合剂、着色剂、除色素剂、软化剂、乳化剂、防脱落剂(exfollient)、成膜剂、香料、致湿剂、驱虫剂、润滑剂、增湿剂、药剂、光稳定剂、防腐剂、皮肤防护剂、皮肤渗透增强剂、遮光剂、稳定剂、表面活性剂、增稠剂、粘度改性剂、维生素,或其任意结合。
本组合物用于产品,尤其是美容品,它减轻皮肤刺激。本发明提供具有治疗特异性的组合物和标准化供给活性成分,通过抑制COX-2酶、NGF蛋白和/或TNF-α蛋白减轻皮肤刺激。本发明组合物可方便地配制成释放稳定浓度的活性成分,或者各成分掺混物,这样可以获得减轻皮肤刺激的预期效果。
本发明通过以下实施例进一步说明。
实施例1
在下述的体外研究中评价本发明的各种天然植物提取物对COX-1酶、NGF和TNF-α的抑制。
环加氧酶抑制过程
植物提取物川芎(Ligusticum chiangxiong Hort.)、日本山茶(Asmunda japonica Thunb.)、冬青、和胶虫树(Butea frondosa Roxb)抑制环加氧酶的功效采用购自Cayman Chemical,商标为COX InhibitorScreening Assay的COX酶免疫测定(EIA)。
每个测试材料的COX反应以背景反应(background reaction)(含有无活性的COX酶)和初始活性反应(含有具有和不具有筛选材料的活性酶)制备。37℃培养10分钟之后,加入作为COX酶底物的花生四烯酸。培养2分钟之后,加入1M HCl停止反应。加入饱和的氯化亚锡溶液(100μL)稳定反应中的前列腺素。
EIA反应通过稀释COX反应制备。EIA缓冲剂加至一些孔中以在加入Cox反应后产生非特异性结合孔。在PG抗血清加至每个孔后将前列腺素(PG)筛选乙酰胆碱酯酶示踪剂加入到孔中。板和所有孔室温培养18小时。在405nm分光光度法测量总活性。下表I提供了试验结果。
TNF-α抑制过程
为了测试冬青、日本山茶、胶虫树(Butea frondosa Roxb.)、和川芎抑制TNF-α生成的功效,采用购自R&D Systems的酶联免疫测定(ELISA)。
这种测定采用定量夹层(sandwich)酶免疫测定技术,其中TNF-α的特异性单克隆抗体已经预涂覆在微量滴定板(microtiter)上。暴露于活性材料的细胞培养上清液移入分离的孔中。上清液内的TNF-α经固定抗体与板结合。在几次洗涤除去未结合抗体后,TNF-α的特异性酶联多克隆抗体加入每个孔。洗涤除去未结合的抗体-酶试剂之后,底物溶液加至孔中。颜色展开与在开始步骤结合的TNF-α数量成比例。表I提供了试验结果。
NGF抑制过程
测试冬青、日本山茶的功效。神经生长因子免疫测定设计成NGF敏感性和特异性检测。平底微量滴定板涂上结合可溶NGF的抗NGF多克隆抗体。捕获的NGF通过第二特异性单克隆抗体结合。洗涤之后,采用结合到辣根过氧化酶(HRP)的种特异性抗体作为第三反应物,检测特异性结合的mAb的量。未结合的结合物通过洗涤除去。以显色底物培养之后,测量颜色变化。测试溶液中NGF的量与氧化还原反应中产生的颜色成比例。表I提供了结果。
表I
体外试验结果
植物提取物 | TNF-α抑制 | COX-2抑制 | NGF抑制 |
冬青 | +++ | ++ | ++++ |
日本山茶(Asmunda japonica Thunb.) | +++ | (0) | ++ |
胶虫树(Butea frondosa Roxb.) | +++ | (0) | ++ |
川芎(Ligusticum chuangxiong Hort.) | +++ | (0) | |
女贞子 | +++ | ||
香榄(Mimusops elengi linn.) | +++ |
图例:
+、++、+++、++++显著抑制(抑制程度通过加号数量量化)
(0)无变化
这些体外研究显示含有冬青、川芎、日本山茶、或胶虫树的提取物的本发明的组合物向皮肤提供抑制COX-2酶、NGF蛋白和/或TNF-α蛋白活性的优点,其中由美容产品、药品或皮肤学产品引起的主观不适和/或刺激会减少,从而使皮肤外观改善。本发明的这些提取物或活性物质在试验量是无毒的。
实施例2
各种活组织检查研究中评价川芎和胶虫树,其中如下阐明的天然植物提取物掺入美容上适合的载体且在研究中施用于参加者的手前臂,剂量2mg/cm2。提取物制剂施用的前臂区接着覆上半闭合片。此过程重复3周,每周5天。治疗末期,该部位以利多卡因麻醉,并从处理和一个未处理的对照部位采取2mm穿孔活组织(punch biopsies)。活组织在福尔马林中固定,嵌入石蜡,切片,相关端点染色。
对于川芎,8个实验对象中的7个显示表皮和皮神经纤维数量的增加(以标记物PGP9.5可见化)。
对于胶虫树,8个实验对象中的5个显示角质细胞增殖增加(由对KI67的抗体可见化),8个实验对象中的5个显示有活力的表皮厚度增加。
实施例3
关于胶虫树炎症挑战研究如下进行:首先测定一组实验对象对于UV和SLS的最小红斑剂量(MED)。制备在载体内含有胶虫树提取物的组合物,该载体包括2份丙二醇、1份乙醇和1份水。该组合物施用至测试实验对象的背部皮肤且令其渗透。此过程重复5连续天,此后一定量UV(背部的一半上)和SLS(另一半)(两者足以正常引起红斑)施用至背部。红斑读数的可视等级确认在这些预治疗试验中胶虫树提取物的抗炎活性优点。相似的女贞子炎症的挑战研究无结论。
先前的描述应当理解为仅举例说明本发明。各种可替代的选择和修正可由本领域技术人员设计而不背离本发明。从而,本发明意图包括所有落入权利要求范围内的可替代的选择、修正和变化。
Claims (54)
1.一种局部组合物,其包括:
美容上、皮肤学上或药学上有效量的至少一种植物提取物,其足以抑制选自COX-2酶、TNF-α蛋白、NGF蛋白及其任意结合的蛋白的活性;和
美容上、皮肤学上或药学上可接受的载体。
2.根据权利要求1所述的组合物,其中所述至少一种植物提取物选自冬青、川芎、日本山茶、女贞子、胶虫树、香榄、及其任意结合。
3.根据权利要求1所述的组合物,其中所述至少一种植物提取物选自冬青、川芎、日本山茶、胶虫树、女贞子、及其任意结合。
4.根据权利要求1所述的组合物,其中所述至少一种植物提取物是冬青和女贞子的掺混物。
5.根据权利要求1所述的组合物,其中所述至少一种植物提取物是胶虫树和川芎的掺混物。
6.根据权利要求1所述的组合物,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.0001wt%至约99wt%。
7.根据权利要求1所述的组合物,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.001wt%至约20wt%。
8.根据权利要求1所述的组合物,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.01wt%至约5wt%。
9.根据权利要求1所述的组合物,其中该组合物为选自气溶胶喷雾剂,霜,乳剂,固体,液体,分散剂,泡沫,凝胶,润肤液,摩丝,软膏,散剂,贴片,香膏剂,溶液,泵送喷雾剂,膏棒,和小毛巾的产品形式。
10.一种局部组合物,其包括:
至少一种有效量的提供其预期美容上、皮肤学或药物反应的美容上、皮肤学上或药物活性成分,所述至少一种活性成分已知引起皮肤刺激症状或病症;
至少一种美容上、皮肤学或药用有效量的植物提取物,其用以减轻由所述至少一种活性成分引起的皮肤刺激症状或病症;和
美容上、皮肤学上或药学上可接受的载体。
11.根据权利要求10所述的组合物,其中所述至少一种植物提取物抑制选自COX-2酶、TNF-α蛋白、NGF蛋白、及其任意结合的蛋白的活性。
12.根据权利要求10所述的组合物,其中所述皮肤刺激症状或病症是至少一种选自红斑、牛皮癣、水肿、色素沉着过度、色素沉着不足、痤疮、疣、轮、斑点、肤色不均、鳞屑、鳞片、痒、灼伤、蜇伤、麻刺感、麻木、风刺激、温度刺激、烟刺激、化学刺激、及其任意结合的症状或病症。
13.根据权利要求10所述的组合物,其中所述至少一种植物提取物选自冬青、川芎、日本山茶、女贞子、胶虫树、香榄,及其任意结合。
14.根据权利要求10所述的组合物,其中所述至少一种植物提取物选自冬青、川芎、日本山茶、女贞子,及其任意结合。
15.根据权利要求10所述的组合物,其中所述至少一种植物提取物是胶虫树和川芎的掺混物。
16.根据权利要求10所述的组合物,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.001wt%至约20wt%。
17.根据权利要求10所述的组合物,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.01wt%至约5wt%。
18.根据权利要求10所述的组合物,其中所述活性成分是皮肤治疗成分。
19.根据权利要求18所述的组合物,其中所述皮肤治疗成分是至少一种选自羟基酸及其衍生物,α-羟基酸,β-羟基酸,类维生素A,及其任意结合的成分。
20.根据权利要求18所述的组合物,其中所述皮肤治疗成分是至少一种选自视黄酸和视黄醇的类维生素A。
21.根据权利要求20所述的组合物,其中所述至少一种类维生素A是视黄醇。
22.根据权利要求18所述的组合物,其中所述皮肤治疗成分是至少一种α-羟基酸,其选自乳酸、羟基乙酸、柠檬酸、苹果酸、酒石酸、苯乙醇酸、阿卓乳酸、葡糖酸、甲基乳酸、苯基乳酸、甘油酸、二苯乙醇酸、2-羟基庚酸、2-羟基辛酸、及其任意结合。
23.根据权利要求18所述的组合物,其中所述皮肤治疗成分是至少一种选自水杨酸和5-n-辛酰基水杨酸的β-羟基酸。
24.一种治疗皮肤刺激症状或病症的方法,其包括向皮肤局部施用美容上、皮肤学上或药学上有效量的权利要求1所述的组合物。
25.根据权利要求24所述的方法,其中所述皮肤刺激症状或病症是至少一种选自红斑、牛皮癣、水肿、色素沉着过度、色素沉着不足、痤疮、疣、轮、斑点、肤色不均、鳞屑、鳞片、痒、灼伤、蜇伤、麻刺感、麻木、风刺激、温度刺激、烟刺激、化学刺激、及其任意结合的症状或病症。
26.根据权利要求24所述的方法,其中所述至少一种植物提取物选自冬青、川芎、日本山茶、女贞子、胶虫树、香榄、及其任意结合。
27.根据权利要求24所述的方法,其中所述至少一种植物提取物选自冬青、川芎、日本山茶、胶虫树、女贞子、及其任意结合。
28.根据权利要求24所述的方法,其中所述至少一种植物提取物是胶虫树和川芎的掺混物。
29.根据权利要求24所述的方法,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.0001wt%至约99wt%。
30.根据权利要求24所述的方法,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.001wt%至约20wt%。
31.根据权利要求24所述的方法,其中所述组合物是选自气溶胶喷雾剂,霜,乳剂,固体,液体,分散剂,泡沫,凝胶,润肤液,摩丝,软膏,散剂,贴片,香膏剂,溶液,泵送喷雾剂,膏棒,和小毛巾的产品形式。
32.根据权利要求24所述的方法,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.01wt%至约5wt%。
33.一种治疗皮肤刺激症状或病症的方法,其包括向皮肤局部施用美容上、皮肤学上或药学上有效量的权利要求10所述的组合物。
34.根据权利要求33所述的方法,其中所述组合物的至少一种植物提取物抑制选自以下的蛋白的活性:COX-2酶、TNF-α蛋白、NGF蛋白、及其任意结合。
35.根据权利要求33所述的方法,其中所述皮肤刺激症状或病症是至少一种选自红斑、牛皮癣、水肿、色素沉着过度、色素沉着不足、痤疮、疣、轮、斑点、肤色不均、鳞屑、鳞片、痒、灼伤、蜇伤、麻刺感、麻木、风刺激、温度刺激、烟刺激、化学刺激,及其任意结合的症状或病症。
36.根据权利要求33所述的方法,其中所述至少一种植物提取物选自冬青、川芎、日本山茶、女贞子、胶虫树、香榄,及其任意结合。
37.根据权利要求33所述的方法,其中所述至少一种植物提取物选自冬青,川芎,日本山茶,胶虫树,女贞子,及其任意结合。
38.根据权利要求33所述的方法,其中所述至少一种植物提取物是胶虫树和川芎的掺混物。
39.根据权利要求33所述的方法,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.0001wt%至约99wt%。
40.根据权利要求33所述的方法,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.001wt%至约20wt%。
41.根据权利要求33所述的方法,其中所述至少一种植物提取物的存在量以所述组合物的总重量计是约0.01wt%至约5wt%。
42.一种局部组合物,其包括:
至少一种选自冬青、川芎、日本山茶、女贞子、胶虫树、香榄及其任意结合的植物提取物,所述至少一种提取物在所述组合物中的存在量是美容上、皮肤学上或药学上改善皮肤美学外观的有效量;和
美容上、皮肤学上或药学上可接受的载体。
43.根据权利要求42所述的组合物,其中所述所述有效量向皮肤有效提供抗老化优点。
44.根据权利要求42所述的组合物,其中所述有效量向皮肤有效提供抗刺激优点。
45.根据权利要求42所述的组合物,其中所述有效量是所述组合物重量的约0.0001wt%至约20wt%。
46.一种改善皮肤美学外观的方法,其包括:
向皮肤施用局部组合物,它包括至少一种选自冬青、川芎、日本山茶、女贞子、胶虫树、香榄、及其任意结合的植物提取物,和
美容上、皮肤学上或药学上可接受的载体,
所述至少一种提取物在所述组合物中的存在量是美容上、皮肤学上或药学上改善皮肤美学外观的有效量。
47.根据权利要求46所述的方法,其中所述有效量向皮肤有效提供抗老化优点。
48.根据权利要求46所述的方法,其中所述有效量向皮肤有效提供抗刺激优点。
49.根据权利要求46所述的方法,其中所述有效量是所述组合物重量的约0.0001wt%至约20wt%,并且在以下一种或多种治疗中有效:
a)减少或预防胶原损失;
b)改善皮肤坚实度/丰满度;
c)改善皮肤质地;
d)减少/预防纹和皱纹;
e)改善肤色;
f)增强皮肤厚度;
g)减小孔径大小;
h)减少皮肤脱色;
i)减少痤疮;
j)减少牛皮癣;
k)减少皮肤敏感性;和
l)减少疣。
50.根据权利要求49所述的方法,其中所述组合物进一步包括至少一种在至少一种a)至l)的病症的治疗中提供其预期的美容上、皮肤学上或药学反应有效量的美容、皮肤学或药物活性成分。
51.根据权利要求50所述的方法,其中所述至少一种活性成分已知引起皮肤刺激症状或病症。
52.根据权利要求47所述的方法,其中所述有效量是所述组合物重量的约0.0001wt%至约20重量%,并且在以下的一种或多种治疗中有效:
a)减少/预防纹和皱纹;
b)增加皮肤厚度;和
c)减少皮肤脱色。
53.根据权利要求52所述的方法,其中所述组合物进一步包括至少一种在至少一种a)至c)的病症的治疗中提供其预期美容上、皮肤学或药学反应有效量的美容、皮肤学或药物活性成分。
54.根据权利要求53所述的方法,其中所述至少一种活性成分已知引起皮肤刺激症状或病症。
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2002
- 2002-12-26 US US10/330,040 patent/US20040126351A1/en not_active Abandoned
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2003
- 2003-12-16 EP EP03814846A patent/EP1575533B1/en not_active Expired - Lifetime
- 2003-12-16 DE DE60327886T patent/DE60327886D1/de not_active Expired - Lifetime
- 2003-12-16 PL PL03371373A patent/PL371373A1/xx not_active Application Discontinuation
- 2003-12-16 WO PCT/US2003/040122 patent/WO2004060288A2/en active Application Filing
- 2003-12-16 AU AU2003297226A patent/AU2003297226B2/en not_active Ceased
- 2003-12-16 AT AT03814846T patent/ATE432696T1/de not_active IP Right Cessation
- 2003-12-16 JP JP2004565537A patent/JP2006508171A/ja active Pending
- 2003-12-16 BR BR0307211-8A patent/BR0307211A/pt not_active Application Discontinuation
- 2003-12-16 CA CA2474608A patent/CA2474608C/en not_active Expired - Fee Related
- 2003-12-16 CN CNA2003801002786A patent/CN1691931A/zh active Pending
-
2004
- 2004-07-22 MX MXPA04007082A patent/MXPA04007082A/es active IP Right Grant
- 2004-07-26 US US10/899,485 patent/US20050048140A1/en not_active Abandoned
-
2006
- 2006-03-13 HK HK06103189.9A patent/HK1083196A1/xx not_active IP Right Cessation
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2009
- 2009-01-05 JP JP2009000330A patent/JP2009137984A/ja active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102271648B (zh) * | 2008-12-29 | 2014-03-12 | 雅芳产品公司 | 包含蜜茱萸的局部组合物和处理皮肤的方法 |
CN109394570A (zh) * | 2018-11-08 | 2019-03-01 | 杭州百芮生物科技有限公司 | 一种超分子水杨酸复合凝胶及其制备方法 |
Also Published As
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EP1575533B1 (en) | 2009-06-03 |
DE60327886D1 (de) | 2009-07-16 |
EP1575533A4 (en) | 2006-12-13 |
AU2003297226A1 (en) | 2004-07-29 |
US20040126351A1 (en) | 2004-07-01 |
JP2006508171A (ja) | 2006-03-09 |
EP1575533A2 (en) | 2005-09-21 |
ATE432696T1 (de) | 2009-06-15 |
CA2474608A1 (en) | 2004-07-22 |
CA2474608C (en) | 2011-08-30 |
JP2009137984A (ja) | 2009-06-25 |
US20050048140A1 (en) | 2005-03-03 |
PL371373A1 (en) | 2005-06-13 |
HK1083196A1 (en) | 2006-06-30 |
WO2004060288A3 (en) | 2004-08-26 |
MXPA04007082A (es) | 2004-10-29 |
BR0307211A (pt) | 2005-02-22 |
WO2004060288A2 (en) | 2004-07-22 |
AU2003297226B2 (en) | 2006-06-15 |
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