CN1355689A - Methods for regulating condition of mammalian keratinous tissue - Google Patents
Methods for regulating condition of mammalian keratinous tissue Download PDFInfo
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- CN1355689A CN1355689A CN00808874A CN00808874A CN1355689A CN 1355689 A CN1355689 A CN 1355689A CN 00808874 A CN00808874 A CN 00808874A CN 00808874 A CN00808874 A CN 00808874A CN 1355689 A CN1355689 A CN 1355689A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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Abstract
本发明涉及调节哺乳动物角质组织状况的各种方法,其中所述方法包括向需要这种处理的哺乳动物角质组织上局部施用安全有效量的包含以下组分的组合物:a)安全有效量的修复剂,所述修复剂基本上由嘌呤化合物组成,所述黄嘌呤化合物选自茶碱,可可碱,和其混合物;和b)用于所述修复剂的皮肤学上可接受的载体。在具体实施方案中,上述组合物适用于调节哺乳动物皮肤质地可见的和/或可触觉的不连续性,防止和/或阻碍哺乳动物皮肤毛细血管和/或红斑的外观,防止和/或阻碍哺乳动物眼下黑圈和松眼泡的外观,防止和/或阻碍哺乳动物肤色灰黄的外观,防止和/或阻碍哺乳动物皮肤下垂,使哺乳动物皮肤脱屑,软化和/或光滑哺乳动物的唇部、毛发和指甲,和防止和/或减轻哺乳动物皮肤的瘙痒。The present invention relates to various methods of modulating the condition of mammalian keratinous tissue, wherein the methods comprise topically applying to the mammalian keratinous tissue in need of such treatment a safe and effective amount of a composition comprising: a) a safe and effective amount of A restorative agent consisting essentially of a purine compound selected from the group consisting of theophylline, theobromine, and mixtures thereof; and b) a dermatologically acceptable carrier for the restorative agent. In particular embodiments, the above compositions are useful for regulating visible and/or tactile discontinuities in the texture of mammalian skin, preventing and/or hindering the appearance of capillaries and/or erythema in mammalian skin, preventing and/or hindering The appearance of dark circles and puffy eyes under the eyes in mammals, prevent and/or hinder the appearance of sallow complexion in mammals, prevent and/or hinder sagging of mammalian skin, desquamation of mammalian skin, soften and/or smoothen the lips of mammals Nails, hair and nails, and prevention and/or relief of itching in mammalian skin.
Description
相关申请的交叉参考Cross References to Related Applications
本申请要求美国临时申请No.60/134,660的利益,后者申请是于1999年5月18日提交的。This application claims the benefit of US Provisional Application No. 60/134,660, filed May 18,1999.
技术领域Technical field
本发明涉及采用选择的黄嘌呤化合物调节哺乳动物角质组织状况的方法,其中该方法包括a)调节哺乳动物皮肤质地可见的和/或可触觉的不连续性,b)防止和/或阻碍哺乳动物皮肤毛细血管和/或红斑的外观,c)防止和/或阻碍哺乳动物眼下黑圈和松眼泡的外观,d)防止和/或阻碍哺乳动物肤色灰黄的外观,e)防止和/或阻碍哺乳动物皮肤下垂,f)使哺乳动物皮肤脱屑,g)软化和/或光滑哺乳动物的唇部、毛发和指甲,和h)防止和/或减轻哺乳动物皮肤的瘙痒。这些方法是通过向需要处理的哺乳动物的角质组织上局部施用含选择的黄嘌呤化合物的组合物来完成的。The present invention relates to a method of modulating the condition of mammalian keratinous tissue using selected xanthine compounds, wherein the method comprises a) modulating visible and/or tactile discontinuities in mammalian skin texture, b) preventing and/or hindering the appearance of skin capillaries and/or erythema, c) prevents and/or hinders the appearance of dark circles and puffy eyes in mammals, d) prevents and/or hinders the appearance of sallow complexion in mammals, e) prevents and/or hinders the appearance of Sagging of mammalian skin, f) desquamation of mammalian skin, g) softening and/or smoothing of mammalian lips, hair and nails, and h) preventing and/or alleviating itching of mammalian skin. These methods are accomplished by topically applying a composition comprising a selected xanthine compound to the keratinous tissue of a mammal in need of treatment.
发明背景Background of the Invention
目前由许多种消费者可以获得的个人护理产品用于改善皮肤的健康和外观。大多数这类产品用于延缓、最少化或甚至消除皮肤皱纹和其它组织性变化,这些状况通常是与皮肤老化或环境对人皮肤的损害相关联的。A wide variety of personal care products are currently available to consumers to improve the health and appearance of the skin. Most of these products are used to delay, minimize or even eliminate skin wrinkling and other tissue changes that are often associated with skin aging or environmental damage to human skin.
哺乳动物角质组织尤其是人的皮肤经受多种外在和内在因素的损害。这些外在因素包括紫外辐射、环境污染、风吹、受热、红外辐射、低湿度、刺激性表面活性剂、磨料等。另一方面,内在因素包括皮肤自身的长期老化和其它生化变化。无论是外在的或内在,这些因素产生皮肤损伤的可见信号。典型的皮肤损伤包括不均匀的质地、毛细血管或红斑、眼下黑圈、松眼泡、肤色灰黄、下垂、死皮、皮肤、毛发、和/或指甲粗糙、和产生瘙痒的皮肤刺激性。Mammalian keratinous tissue, especially human skin, is damaged by a variety of extrinsic and intrinsic factors. These external factors include ultraviolet radiation, environmental pollution, wind, heat, infrared radiation, low humidity, irritating surfactants, abrasives, etc. Intrinsic factors, on the other hand, include long-term aging and other biochemical changes in the skin itself. Whether extrinsic or intrinsic, these factors produce visible signs of skin damage. Typical skin lesions include uneven texture, capillary or erythema, dark circles under the eyes, puffy eyes, sallow complexion, sagging, dead skin, rough skin, hair, and/or nails, and itchy skin irritation.
因此,需要能处理这些角质组织状况的产品和方法,使所述如皮肤、毛发和指甲的角质组织的状况得到调节。Accordingly, there is a need for products and methods that address the condition of these keratinous tissues, such as skin, hair and nails, so that the condition of said keratinous tissues is regulated.
申请人现已发现,含有某些黄嘌呤化合物的局部用组合物可用于预防性和治疗性地处理这类角质组织状况。例如,申请人已发现这类组合物用于处理皮肤不均匀的质地、毛细血管或红斑、眼下黑圈、松眼泡、肤色灰黄、皮肤下垂、死皮、粗糙的角质组织,包括但不限于皮肤、毛发、和/或指甲、和产生瘙痒的皮肤刺激性。Applicants have now discovered that topical compositions containing certain xanthine compounds are useful for the prophylactic and therapeutic management of such keratinous tissue conditions. For example, Applicants have discovered that such compositions are useful in the treatment of uneven skin texture, capillary or erythema, dark circles under the eyes, puffy eyes, sallow complexion, sagging skin, dead skin, rough keratinous tissue, including but not limited to Skin, hair, and/or nails, and itchy skin irritation.
发明概述Invention Summary
本发明涉及调节哺乳动物角质组织状况的方法,其中该方法包括向需要这种处理的哺乳动物角质组织上局部施用安全有效量的包含以下组分的组合物:The present invention relates to a method of regulating the condition of mammalian keratinous tissue, wherein the method comprises topically applying to the mammalian keratinous tissue in need of such treatment a safe and effective amount of a composition comprising:
a)安全有效量的修复剂,所述修复剂基本上由黄嘌呤化合物a) a safe and effective amount of restorative, which consists essentially of xanthine compounds
组成,所述黄嘌呤化合物选自茶碱,可可碱,和其混合物;Composition, the xanthine compound is selected from theophylline, theobromine, and mixtures thereof;
和 and
b)用于所述修复剂的皮肤学上可接受的载体。b) A dermatologically acceptable carrier for the restorative agent.
在特定实施方案中,上述组合物或其改性形式适用于调节哺乳动物皮肤质地可见的和/或可触觉的不连续性,防止和/或阻碍哺乳动物皮肤毛细血管和/或红斑的外观,防止和/或阻碍哺乳动物眼下黑圈和松眼泡的外观,防止和/或阻碍哺乳动物肤色灰黄的外观,防止和/或阻碍哺乳动物皮肤下垂,使哺乳动物皮肤脱屑,软化和/或光滑哺乳动物的唇部、毛发和指甲,和防止和/或减轻哺乳动物皮肤的瘙痒。In particular embodiments, the above compositions or modifications thereof are suitable for modulating visible and/or tactile discontinuities in the texture of mammalian skin, preventing and/or obstructing the appearance of capillaries and/or erythema in mammalian skin, Prevents and/or hinders the appearance of dark circles and puffy eyes under the eyes in mammals, prevents and/or hinders the appearance of sallow complexion in mammals, prevents and/or hinders the appearance of sagging mammalian skin, desquamates mammalian skin, softens and/or Smoothes the lips, hair and nails of mammals, and prevents and/or relieves itching of mammalian skin.
发明详述Detailed description of the invention
这里所有百分数和比率,按照组合物总重量计,所有测定在25℃下进行,除非另有说明。All percentages and ratios herein are by weight of the total composition and all measurements made are at 25°C unless otherwise indicated.
本发明的组合物可包含基本成分及这里所述非必选成份和组分,或由这些成分组成或基本上由这些成分组成。这里所述“基本上由这些成分组成”是指组合物或组分可以包含其它成分,只要该其它成分不明显改变要求保护的组合物或方法的基本的和新颖的特性。The compositions of the present invention may comprise, consist of, or consist essentially of the essential ingredients and the optional ingredients and components described herein. Here, "consisting essentially of these ingredients" means that the composition or component may contain other ingredients, as long as the other ingredients do not significantly change the basic and novel characteristics of the claimed composition or method.
这里所引用的出版物因此全文引入作为参考The publications cited herein are hereby incorporated by reference in their entirety
术语“角质组织”在本文中是指含有角蛋白的置于哺乳动物的最外层的保护覆盖层,它包括但不限于皮肤、毛发、和指甲(如脚趾甲、手指甲、蹄、表皮等部位)。The term "keratinous tissue" as used herein refers to the outermost protective covering of mammals containing keratin, which includes, but is not limited to, skin, hair, and nails (such as toenails, fingernails, hooves, cuticles, etc. parts).
这里“局部施用”指向哺乳动物角质组织表面施用或铺展本发明的组合物。"Topical application" herein refers to applying or spreading the composition of the present invention on the surface of mammalian keratinous tissue.
这里术语“皮肤学上可接受的”指所述组合物或组分适于与人体角质组织接触,没有不当的毒性、不相容性、不稳定性、过敏反应等。The term "dermatologically acceptable" herein means that the composition or component is suitable for contact with human keratinous tissue without undue toxicity, incompatibility, instability, allergic reaction, and the like.
这里术语“安全及有效量”指这样的化合物或组合物用量,它能明显产生有益效果,优选有益的角质组织外观或肤感效果,独立地包括这里所说的各种益处,但是能避免严重的副作用,如产生合理益害比,该用量是在技术人员的合理判断的范围内。The term "safe and effective amount" herein refers to an amount of a compound or composition that significantly produces a beneficial effect, preferably a beneficial keratinous tissue appearance or skin feel effect, independently including the various benefits mentioned herein, but avoiding severe If there is a reasonable benefit-harm ratio, the dosage is within the reasonable judgment of the technical personnel.
这里的“脱屑、剥离和/或增进更新率”是指除去角质层(包括角状层和粒面层)的最上层。不受理解限制,认为这类效果可以通过物理和化学方式完成,这些方式从上至下除去所述层。另外,可以通过生物学方式引起剥离,该方式促进从基础层向上的表皮层的更新。认为这会引起角化细胞再生和诱导分化的过程。后者导致角质化程度的提高以及最终导致上表皮层包括角质层和粒面层的再构。"Desquamation, exfoliation and/or enhanced turnover" herein refers to removal of the uppermost layer of the stratum corneum (including the stratum corneum and the stratum corneum). Without being limited by understanding, it is believed that such effects can be accomplished by physical and chemical means, which remove the layers from top to bottom. In addition, exfoliation can be induced by biological means that promote the renewal of the epidermal layer from the basal layer upwards. This is thought to trigger the process of keratinocyte regeneration and induction of differentiation. The latter leads to an increased degree of keratinization and ultimately to a remodeling of the upper epidermal layers, including the stratum corneum and the grain layer.
术语“下垂”在本文是指皮肤的松弛、松散及类似情况,这是由于皮肤弹性硬蛋白的损失、损坏、改变和/或异常造成的。The term "sagging" as used herein refers to laxity, looseness and the like of the skin due to loss, damage, alteration and/or abnormality of the elastin of the skin.
术语“光滑”和“软化”在本文是指改变角质组织的表面以改善其触觉效果。The terms "smooth" and "softening" herein refer to modifying the surface of keratinous tissue to improve its tactile effect.
本发明组合物适用于局部施用和适用于调节角质组织状况。调节角质组织状况通常是所需求的,因为身体外和/或体内的各种因素造成这些状况。具体说,“调节皮肤状况”包括预防性和/或治疗性调节皮肤状况,包括防止皮肤弹性的损失(功能性皮肤弹性硬蛋白的损失和/或失活),如弹性组织变性、下垂、由于变形的皮肤回弹性丧失;非黑色素皮肤的变色如眼下黑圈、斑(如由于酒渣鼻的不均匀的变红)、肤色灰黄(浅色)、由于毛细血管或其扩张引起的变色。这里使用的预防性调节皮肤状况包括延缓、最少化和/或防止皮肤可见的和/或可触觉的不连续性。这里使用的治疗性调节皮肤状况包括改善如减少、最少化和/或消除皮肤的不连续性。调节皮肤状况涉及改善皮肤,尤其是面部皮肤外观和/或感受(即调节哺乳动物皮肤质地可见的和/或可触觉的不连续性。The compositions of the present invention are suitable for topical application and for regulating the condition of keratinous tissue. Regulating the condition of keratinous tissue is often desired because various factors outside the body and/or inside the body contribute to these conditions. Specifically, "regulation of skin condition" includes prophylactic and/or therapeutic regulation of skin condition, including prevention of loss of skin elasticity (loss and/or inactivation of functional skin elastin), such as elastosis, sagging, due to Distorted skin with loss of resilience; discoloration of non-melanotic skin such as dark circles under the eyes, spots (eg, uneven reddening due to rosacea), sallow (lighter) complexion, discoloration due to capillaries or their dilatation. As used herein, prophylactic regulation of skin condition includes delaying, minimizing and/or preventing visible and/or tactile discontinuities in the skin. As used herein, therapeutically regulating skin condition includes improving, eg reducing, minimizing and/or eliminating skin discontinuities. Regulating skin condition involves improving skin, especially facial skin appearance and/or feel (ie, modulating visible and/or tactile discontinuities in mammalian skin texture.
这里使用的“调节皮肤状况”包括调节与起源机理无关的这类信号。As used herein, "regulating skin condition" includes modulating such signals independent of the mechanism of origin.
本发明组合物包括基本组分和任选组分,在以下详述。黄嘌呤化合物The compositions of the present invention comprise essential components and optional components, as detailed below. xanthine compounds
本发明局部用组合物可包含安全有效量的各种修复剂,所述修复剂基本上由黄嘌呤化合物组成,所述黄嘌呤化合物选自茶碱,可可碱,和其混合物。The topical compositions of the present invention may contain a safe and effective amount of various restorative agents consisting essentially of xanthine compounds selected from the group consisting of theophylline, theobromine, and mixtures thereof.
茶碱(也称为3,7-二氢-1,3,-二甲基-1H-嘌呤-2,6-二酮或1,3-二甲基黄嘌呤)和可可碱(也称为3,7-二氢-3,7-二甲基-1H-嘌呤-2,6-二酮)商购自Sigma化学公司(St.Louis,MO);Aldrich化学公司(Milwaukee,WI)和Fluka Chemika-USA(Ronkonkonma,NY)。Theophylline (also known as 3,7-dihydro-1,3,-dimethyl-1H-purine-2,6-dione or 1,3-dimethylxanthine) and theobromine (also known as 3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione) was purchased from Sigma Chemical Company (St.Louis, MO); Aldrich Chemical Company (Milwaukee, WI) and Fluka Chemika-USA (Ronkonkonma, NY).
在本发明组合物中,所述黄嘌呤化合物优选占组合物重量约0.01%至约50%,更优选约0.1%至约20%,再优选约1%至约10%,再优选约2%至约8%,最优选约4%至约6%。In the composition of the present invention, the xanthine compound preferably accounts for about 0.01% to about 50% by weight of the composition, more preferably about 0.1% to about 20%, more preferably about 1% to about 10%, more preferably about 2% to about 8%, most preferably from about 4% to about 6%.
不受理论限制,认为这些黄嘌呤化合物增加了表皮的更新率,这又导致了皮肤,尤其是面部皮肤的质地外观的最终改进。认为这些黄嘌呤化合物的作用机理涉及细胞的环状腺苷单磷酸(cAMP)含量的增加,这诱导了二级信号途径,例如增加了细胞间磷酸钙和肌醇磷酸酯的形成。最终,这导致了基因表达模式的改变,这影响了细胞体内平衡。Without being limited by theory, it is believed that these xanthine compounds increase the turnover rate of the epidermis, which in turn leads to an eventual improvement in the textural appearance of the skin, especially facial skin. The mechanism of action of these xanthine compounds is thought to involve an increase in cellular cyclic adenosine monophosphate (cAMP) content, which induces secondary signaling pathways, such as increased intercellular calcium phosphate and inositol phosphate formation. Ultimately, this leads to changes in gene expression patterns, which affect cellular homeostasis.
皮肤学上可接受的载体Dermatologically acceptable carrier
本发明局部用组合物还包含用于所述黄嘌呤化合物的皮肤学上可接受的载体。这里术语“皮肤学上可接受的载体”指该载体适用于哺乳动物的角质组织的局部施用,具有良好的美观性能,与本发明的活性物及任何其它组分相容,并且不会引起任何不期望的安全或毒性问题。安全有效量的载体为组合物重量的约50%至约99.99%,优选约80%至约99.9%,更优选约90%至约98%,最优选约90%至约95%。The topical compositions of the present invention also comprise a dermatologically acceptable carrier for the xanthine compound. The term "dermatologically acceptable carrier" herein means that the carrier is suitable for topical application to mammalian keratinous tissue, has good aesthetic properties, is compatible with the actives of the present invention and any other components, and does not cause any Unexpected safety or toxicity concerns. A safe and effective amount of carrier is from about 50% to about 99.99%, preferably from about 80% to about 99.9%, more preferably from about 90% to about 98%, most preferably from about 90% to about 95%, by weight of the composition.
载体可以是多种形式。例如,乳液载体包括但不限于水包油、油包水、水包油包水和聚硅氧烷包水包油乳液适用于此。Carriers can take many forms. For example, emulsion carriers including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions are suitable herein.
优选的载体包括乳液,如水包油乳液或油包水乳液(如水包聚硅氧烷或聚硅氧烷包水)。本领域技术人员可以理解,给定组分将主要分布于水或油相,这取决于组合物中组分的水溶性/分散性。所述黄嘌呤化合物主要分散在油相中。尤其优选水包油乳液。Preferred carriers include emulsions, such as oil-in-water emulsions or water-in-oil emulsions (eg, silicone-in-water or water-in-silicone). Those skilled in the art will appreciate that a given component will distribute primarily in the water or oil phase, depending on the water solubility/dispersibility of the component in the composition. The xanthine compounds are mainly dispersed in the oil phase. Oil-in-water emulsions are especially preferred.
本发明乳液一般含上述溶液和脂质或油。脂质和油可来自于动物、植物或石油,可以是天然的或合成的(即人造的)。优选的乳液也含润湿剂,如甘油。乳液优选还含约1%至约10%,更优选约2%至约5%的乳化剂,基于载体重量。乳化剂可以是非离子的、阴离子的或阳离子的。适宜的乳化剂公开于,例如1973年8月28日授权Dickert等人的USP 3755560;1983年12月20日授权Dixon等人的USP 4421769;和McCutcheon的洗涤剂和乳化剂,北美版,第317-324页(1986)。Emulsions of the present invention generally comprise the solutions described above and lipids or oils. Lipids and oils can be of animal, vegetable or petroleum origin, and can be natural or synthetic (ie, man-made). Preferred emulsions also contain humectants such as glycerin. The emulsion preferably also contains from about 1% to about 10%, more preferably from about 2% to about 5%, of an emulsifier, based on the weight of the carrier. Emulsifiers can be nonionic, anionic or cationic. Suitable emulsifiers are disclosed, for example, in USP 3755560, issued August 28, 1973 to Dickert et al; USP 4421769, issued December 20, 1983 to Dixon et al; and McCutcheon's Detergents and Emulsifiers, North American Edition, p. 317 - 324 pages (1986).
乳液还可含有消泡剂,使施用于皮肤时最少泡沫形成。消泡剂包括高分子量聚硅氧烷,和其它本领域已知的用于此的物质。Lotions may also contain antifoaming agents to minimize foam formation when applied to the skin. Antifoaming agents include high molecular weight polysiloxanes, and others known in the art to be useful therefor.
以下更详细描述优选的聚硅氧烷包水和水包油乳液。Preferred water-in-silicone and oil-in-water emulsions are described in more detail below.
a)聚硅氧烷包水乳液a) Water-in-silicone emulsion
聚硅氧烷包水乳液含连续的聚硅氧烷相和分散的水相。Water-in-silicone emulsions contain a continuous silicone phase and a dispersed aqueous phase.
(i)连续的聚硅氧烷相(i) Continuous polysiloxane phase
本发明优选的聚硅氧烷包水乳液包含约1%至约60%,优选约5%至约40%,更优选约10%至约20%重的连续聚硅氧烷相。连续的聚硅氧烷相以外相存在,它包含或围绕着下述的不连续的水相。Preferred water-in-silicone emulsions of the present invention comprise from about 1% to about 60%, preferably from about 5% to about 40%, more preferably from about 10% to about 20%, by weight, of the continuous silicone phase. The continuous polysiloxane phase exists as an external phase which contains or surrounds the discontinuous aqueous phase described below.
连续的聚硅氧烷相含聚有机基硅氧烷油。配制优选的聚硅氧烷包油乳液体系以为任选的类视色素提供氧化稳定的载体。这些优选的乳液的连续聚硅氧烷相包含约50%至约99.9%重的有机基聚硅氧烷油和低于约50%重的非聚硅氧烷油。在尤其优选的实施方案中,连续聚硅氧烷相包含至少约50%,优选约60%至约99.9%,更优选约70%至约99.9%,尤其优选80%至约99.9%的聚有机基硅氧烷油,和至多约50%非聚硅氧烷油,优选小于约40%,更优选小于约30%,更优选小于约10%,和再优选小于约2%,基于连续聚硅氧烷相重量。这些优选的乳液体系与可比的含较低浓度聚有机基硅氧烷油的油包水乳液相比,提供了在较长时间内的对类视色素的更强氧化稳定性。在连续聚硅氧烷相中的非聚硅氧烷油的浓度被最低化或避免在一起以进一步增强组合物中所选类视色素的氧化稳定性。这种类型的聚硅氧烷包油乳液描述于1995年12月11日提交的共同待审美国专利申请No.08/570,275,以Joseph Michael Znkowski、Brent William Mason、Larry Richard Robinsin和Greg George Hillebrand的名义。The continuous silicone phase contains organopolysiloxane oil. The preferred oil-in-silicone emulsion systems are formulated to provide an oxidatively stable carrier for the optional retinoid. The continuous silicone phase of these preferred emulsions comprises from about 50% to about 99.9% by weight organopolysiloxane oil and less than about 50% by weight non-silicone oil. In an especially preferred embodiment, the continuous polysiloxane phase comprises at least about 50%, preferably from about 60% to about 99.9%, more preferably from about 70% to about 99.9%, and especially preferably from 80% to about 99.9% polyorganic Silicone-based oils, and up to about 50% non-silicone oils, preferably less than about 40%, more preferably less than about 30%, more preferably less than about 10%, and still more preferably less than about 2%, based on the continuous silicone Oxane phase weight. These preferred emulsion systems provide greater oxidative stability to retinoids over longer periods of time than comparable water-in-oil emulsions containing lower concentrations of organosiloxane oil. The concentration of non-silicone oils in the continuous silicone phase is minimized or avoided together to further enhance the oxidative stability of the selected retinoids in the composition. Oil-in-silicone emulsions of this type are described in co-pending U.S. Patent Application No. 08/570,275, filed December 11, 1995, to Joseph Michael Znkowski, Brent William Mason, Larry Richard Robinsin, and Greg George Hillebrand. name.
组合物中聚有机基硅氧烷油可以是挥发性的非挥发性的、或挥发性的与非挥发性的聚硅氧烷的混合物。术语“非挥发性的”在本文指那些在室温下为液态并具有100℃或更高的闪点(在一个大气压下)的聚硅氧烷。术语“挥发性的”在本文指所有其它的聚硅氧烷油。适宜的聚有机基硅氧烷可选自多种聚硅氧烷,跨越宽的挥发性和粘度范围。适合的聚有机基硅氧烷油包括聚烷基硅氧烷、环状聚烷基硅氧烷和聚烷基芳基硅氧烷。The organopolysiloxane oil in the composition can be a volatile non-volatile or a mixture of volatile and non-volatile polysiloxanes. The term "nonvolatile" refers herein to those polysiloxanes which are liquid at room temperature and have a flash point (at one atmosphere) of 100°C or higher. The term "volatile" refers herein to all other silicone oils. Suitable organopolysiloxanes can be selected from a wide variety of polysiloxanes spanning a wide range of volatility and viscosity. Suitable polyorganosiloxane oils include polyalkylsiloxanes, cyclic polyalkylsiloxanes and polyalkylarylsiloxanes.
该组合物中聚烷基硅氧烷包括在25℃粘度约0.5至约1,000,000厘沲的聚烷基硅氧烷。这类聚烷基硅氧烷可以通式R3SiO[R2SiO]xSiR3代表,其中R为C1-C30的烷基(优选R为甲基或乙基,更优选甲基;在同一分子中也可以存在不同的烷基),x为0至约10,000的整数,选择x可以获得所需的可达约10,000,000以上的分子量。商购聚烷基硅氧烷包括聚二甲基硅氧烷,也称二甲聚硅氧烷,其实例包括通用电气公司出售的Vicasil系列,和道康宁公司出售的Dow Corning200系列。合适的聚二甲基硅氧烷的具体实例包括Dow Corning200流体,其粘度0.65厘沲,沸点100℃,DowCorning225流体,粘度10厘沲,沸点大于200℃,和Dow Corning200流体,粘度分别为50,350和12,500厘沲,沸点大于200℃。合适的二甲聚硅氧烷包括那些化学式(CH3)3SiO[(CH3)2SiO]x[CH3RSiO]ySi(CH3)3代表的,其中R为2至30个碳原子的直链或支链,x和y各为1或更大的整数,选择x和y可以获得可达约10,000,000以上的所需的分子量。这些烷基取代的二甲聚硅氧烷的实例包括鲸蜡基二甲聚硅氧烷和月桂基二甲聚硅氧烷。The polyalkylsiloxanes in the composition include polyalkylsiloxanes having a viscosity of from about 0.5 to about 1,000,000 centistokes at 25°C. This type of polyalkylsiloxane can be represented by the general formula R 3 SiO[R 2 SiO] x SiR 3 , wherein R is a C1-C30 alkyl group (preferably R is methyl or ethyl, more preferably methyl; in the same There may also be different alkyl groups in the molecule), x is an integer from 0 to about 10,000, x can be selected to obtain the desired molecular weight up to about 10,000,000 or more. Commercially available polyalkylsiloxanes include polydimethylsiloxanes, also known as dimethicones, examples of which include the Vicasil (R) series sold by General Electric Company, and the Dow Corning( R) 200 series sold by Dow Corning Corporation. Specific examples of suitable polydimethylsiloxanes include Dow Corning® 200 fluid, which has a viscosity of 0.65 centistokes and a boiling point of 100°C, Dow Corning® 225 fluid, which has a viscosity of 10 centistokes and a boiling point of greater than 200°C, and Dow Corning® 200 fluid , the viscosities are 50, 350 and 12,500 centistokes respectively, and the boiling point is greater than 200°C. Suitable dimethicones include those represented by the formula (CH 3 ) 3 SiO[(CH 3 ) 2 SiO] x [CH 3 RSiO] y Si(CH 3 ) 3 wherein R is 2 to 30 carbon atoms The linear or branched chain, x and y are each an integer of 1 or more, and x and y can be selected to obtain a desired molecular weight up to about 10,000,000 or more. Examples of these alkyl-substituted dimethicones include cetyl dimethicone and lauryl dimethicone.
适用于组合物的环状聚烷基硅氧烷包括那些化学式[SiR2-O]n代表的,其中R为烷基(优选R为甲基或乙基,更优选甲基),和n为约3至约8的整数,更优选约3至约7的整数,和最优选约4至约6的整数。当R为甲基时,这些物质一般被称为环甲聚硅氧烷。商购环甲聚硅氧烷包括Dow Corning244流体,粘度2.5厘沲,沸点172℃,它主要含环甲四聚硅氧烷(即n=4),DowCorning344流体,粘度2.5厘沲,沸点178℃,它主要含环甲五聚硅氧烷(即n=5),Dow Corning245流体,粘度4.2厘沲,沸点205℃,它主要含环甲四聚硅氧烷和环甲五聚硅氧烷(即n=4和5)的混合物,和DowCorning345流体,粘度4.5厘沲,沸点217℃,它主要含环甲四聚硅氧烷、环甲五聚硅氧烷和环甲六聚硅氧烷(即n=4、5和6)的混合物。Cyclic polyalkylsiloxanes suitable for use in the composition include those represented by the formula [ SiR2 -O] n , wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl), and n is An integer of about 3 to about 8, more preferably an integer of about 3 to about 7, and most preferably an integer of about 4 to about 6. When R is methyl, these materials are generally known as cyclomethicones. Commercially available cyclomethicones include Dow Corning ® 244 fluid, viscosity 2.5 centistokes, boiling point 172°C, which mainly contains cyclomethicone (i.e., n=4), Dow Corning ® 344 fluid, viscosity 2.5 centistokes , boiling point 178°C, it mainly contains cyclomethicone (ie n=5), Dow Corning ® 245 fluid, viscosity 4.2 centistokes, boiling point 205°C, it mainly contains cyclomethicone and cyclomethicone A mixture of pentapolysiloxane (i.e. n = 4 and 5), and DowCorning® 345 fluid, viscosity 4.5 centistokes, boiling point 217 ° C, it mainly contains cyclomethicone, cyclomethicone and Mixtures of cyclomethicones (ie n = 4, 5 and 6).
如三甲基硅氧基硅酸酯的物质也适用,它是对应于通式[(CH2)3SiO1/2]x[SiO2]y的聚合物,其中x为约1至约500的整数,y为约1至约500的整数。商购三甲基硅氧基硅酸酯是作为与二甲聚硅氧烷DowCorning593流体的混合物出售的。Also suitable are materials such as trimethylsiloxysilicate, which is a polymer corresponding to the general formula [(CH 2 ) 3 SiO 1/2 ] x [SiO 2 ] y , where x is from about 1 to about 500 is an integer, y is an integer from about 1 to about 500. Commercially available trimethylsiloxysilicate is sold as a mixture with the dimethicone DowCorning (R) 593 Fluid.
二甲聚硅氧烷醇也适用于组合物。这类化合物可用化学式R3SiO[R2SiO]xSiR2OH和HOR2SiO[R2SiO]xSiR2OH表示,其中R为烷基(优选R为甲基或乙基,更优选甲基)和x为0至约500的整数,选择x以获得所需的分子量。商购二甲聚硅氧烷一般是以与二甲聚硅氧烷或环甲聚硅氧烷的混合物出售(如Dow Corning1401、1402和1403流体)。Dimethiconol is also suitable for use in the composition. Such compounds can be represented by chemical formulas R 3 SiO[R 2 SiO] x SiR 2 OH and HOR 2 SiO[R 2 SiO] x SiR 2 OH, wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl base) and x is an integer from 0 to about 500, x is selected to obtain the desired molecular weight. Commercially available dimethicones are generally sold as mixtures with dimethicone or cyclomethicone (eg Dow Corning (R) 1401, 1402 and 1403 fluids).
聚烷基芳基硅氧烷也适用于组合物。尤其是粘度约15至约65厘沲(25℃)的聚甲基苯基硅氧烷。Polyalkylaryl siloxanes are also suitable for use in the composition. Especially polymethylphenylsiloxanes having a viscosity of from about 15 to about 65 centistokes (25°C).
这里优选的聚有机基硅氧烷选自:聚烷基硅氧烷、烷基取代的二甲聚硅氧烷、环甲聚硅氧烷、三甲基硅氧烷硅酸酯、二甲聚硅氧烷醇、聚烷基芳基硅氧烷及其混合物。这里更优选聚烷基硅氧烷和环甲聚硅氧烷。在聚烷基硅氧烷中优选的是二甲聚硅氧烷。Preferred polyorganosiloxanes herein are selected from the group consisting of polyalkylsiloxanes, alkyl substituted dimethicones, cyclomethicones, trimethicone silicates, dimethicone Silicone alcohols, polyalkylaryl siloxanes and mixtures thereof. More preference is given here to polyalkylsiloxanes and cyclomethicones. Preferred among the polyalkylsiloxanes are dimethicones.
如上所述,连续聚硅氧烷相可含一种或多种非聚硅氧烷油。在连续聚硅氧烷相中非聚硅氧烷油的浓度优选最小化或被避免在一起,以更进一步增强组合物中所选的类视色素的氧化稳定性。合适的非聚硅氧烷油的在约1个大气压下的熔点为约25℃或更低。用于连续聚硅氧烷相的非聚硅氧烷油的实例是局部用个人护理产品的化学领域中熟知的那些,其中产品是以油包水乳液形式,例如矿物油、植物油、合成油、半合成油等。As noted above, the continuous silicone phase may contain one or more non-silicone oils. The concentration of non-silicone oils in the continuous silicone phase is preferably minimized or avoided together to even further enhance the oxidative stability of the selected retinoid in the composition. Suitable non-silicone oils have a melting point of about 25°C or less at about 1 atmosphere. Examples of non-silicone oils for the continuous silicone phase are those well known in the chemical art of topical personal care products, where the product is in the form of a water-in-oil emulsion, such as mineral oils, vegetable oils, synthetic oils, Semi-synthetic oil etc.
(ii)分散的水相(ii) Dispersed aqueous phase
本发明的局部用组合物包含约30%至约90%,更优选约50%至约85%,最优选约70%至约80%的分散的水相。在乳液技术中,术语“分散相”是本领域技术人员熟知的术语,它指悬浮于或被包围于连续相中的小颗粒或液滴。分散相也称为内相或不连续相。分散的水相是悬浮于或被包围于上述连续聚硅氧烷相中的小水滴或颗粒分散体。The topical compositions of the present invention comprise from about 30% to about 90%, more preferably from about 50% to about 85%, most preferably from about 70% to about 80%, of a dispersed aqueous phase. In emulsion technology, the term "dispersed phase" is a term well known to those skilled in the art and refers to small particles or droplets suspended or surrounded in a continuous phase. The dispersed phase is also called the internal or discontinuous phase. The dispersed aqueous phase is a dispersion of water droplets or particles suspended or surrounded in the above-mentioned continuous polysiloxane phase.
水相可以是水,或水和一种或多种水可溶或水可分散成分的结合。这类成分的非限制性实例包括增稠剂、酸、碱、盐、螯合剂、胶、水溶性或水分散性醇和多元醇、缓冲剂、防腐剂、防晒剂、色料等。The aqueous phase can be water, or a combination of water and one or more water-soluble or water-dispersible ingredients. Non-limiting examples of such ingredients include thickeners, acids, bases, salts, chelating agents, gums, water-soluble or water-dispersible alcohols and polyols, buffers, preservatives, sunscreens, colorants, and the like.
本发明局部用组合物一般包含约25%至约90%,优选约40%至约80%,更优选约60%至约80%的在分散的水相中的水,按组合物重量计。The topical compositions of the present invention generally comprise from about 25% to about 90%, preferably from about 40% to about 80%, more preferably from about 60% to about 80%, water in the dispersed aqueous phase, by weight of the composition.
(iii)分散水相的乳化剂(iii) Emulsifier for dispersing the aqueous phase
本发明的聚硅氧烷包水乳液优选包括乳化剂。在优选的实施方案中,组合物含约0.1%至约10%的乳化剂,更优选约0.5%至约7.5%,最优选约1%至约5%的乳化剂,按组合物重量计。乳化剂有助于将水相分散和悬浮于连续的聚硅氧烷相中。The water-in-silicone emulsions of the present invention preferably include an emulsifier. In a preferred embodiment, the compositions contain from about 0.1% to about 10% emulsifier, more preferably from about 0.5% to about 7.5%, most preferably from about 1% to about 5%, by weight of the composition. Emulsifiers help to disperse and suspend the aqueous phase in the continuous silicone phase.
这里可以采用多种乳化剂,以形成优选的聚硅氧烷包水乳液。已知的或传统的乳化剂可用于该组合物,只要所选的乳化剂与组合物的基本成分是化学上和物理上相容的,并且产生了所需的分散性能。合适的乳化剂包括聚硅氧烷乳化剂,不含硅的乳化剂及其混合物,它们是局部用个人护理产品领域的技术人员已知的。优选地,这些乳化剂具有小于约14的HLB值,更优选约2至约14,最优选约4至约14。HLB值不在该范围内的乳化剂可以与其它乳化剂结合使用,以达到落入该范围的组合的有效重均HLB。A variety of emulsifiers can be employed herein to form the preferred water-in-silicone emulsions. Known or conventional emulsifiers can be used in the composition provided that the emulsifier selected is chemically and physically compatible with the essential ingredients of the composition and produces the desired dispersing properties. Suitable emulsifiers include silicone emulsifiers, silicone-free emulsifiers and mixtures thereof, which are known to those skilled in the topical personal care product art. Preferably, these emulsifiers have an HLB value of less than about 14, more preferably from about 2 to about 14, most preferably from about 4 to about 14. Emulsifiers with HLB values outside this range can be used in combination with other emulsifiers to achieve a combined effective weight average HLB within this range.
优选聚硅氧烷乳化剂。这里使用多种聚硅氧烷乳化剂。这些聚硅氧烷乳化剂一般是有机改性的有机基聚硅氧烷,本领域技术人员也称之为聚硅氧烷表面活性剂。适用的聚硅氧烷乳化剂包括二甲聚硅氧烷共聚多元醇。这些物质是这样的聚二甲基硅氧烷,它们已被改性以包括聚醚侧链,如聚环氧乙烷链、聚环氧丙烷链,这些链的混合物,以及含有同时衍生自环氧乙烷和环氧丙烷的部分的聚醚链。其它实例包括烷基改性的二甲聚硅氧烷共聚多元醇,即含C2-C30侧链的化合物。其它适用的二甲聚硅氧烷共聚多元醇还包括具有各种阳离子、阴离子、两性和两性离子侧基部分的物质。Silicone emulsifiers are preferred. A variety of silicone emulsifiers are used herein. These silicone emulsifiers are generally organically modified organopolysiloxanes, also known as silicone surfactants by those skilled in the art. Suitable silicone emulsifiers include dimethicone copolyols. These materials are polydimethylsiloxanes which have been modified to include polyether side chains such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and Polyether chains that are part of ethylene oxide and propylene oxide. Other examples include alkyl-modified dimethicone copolyols, ie, compounds containing C2-C30 side chains. Other suitable dimethicone copolyols include those having various pendant cationic, anionic, amphoteric and zwitterionic moieties.
这里采用的二甲聚硅氧烷共聚多元醇乳化剂可用下式表示: The dimethicone copolyol emulsifier used here can be represented by the following formula:
其中R为C1-C30直链、支链或环状烷基,和R2选自由以下组成的基团:Wherein R is C1-C30 linear, branched or cyclic alkyl, and R2 is selected from groups consisting of:
--(CH2)n--O--(CH2CHR3O)m--H,--(CH 2 ) n --O --(CH 2 CHR 3 O) m --H,
和and
--(CH2)n--O--(CH2CHR3O)m--(CH2CHR4O)o--H,--(CH 2 ) n --O--(CH 2 CHR 3 O) m --(CH 2 CHR 4 O) o --H,
其中n为3至约10的整数;R3和R4选自由H和C1-C16直链或支链烷基组成的基团,使得R3和R4不同时一样;和m、o、x和y的选择使得分子具有约200至约10,000,000的整体分子量,并且m、o、x和y各自选自零或更大的整数,使m和o不同时为零,和z独自选自1或更大的整数。认识到可以获得这些共聚多元醇的位置异构体。上述含有R3和R4基团的R2部分的化学代表式并不是限制性的,而是为了方便而示出来的。wherein n is an integer from 3 to about 10; R and R are selected from groups consisting of H and C1-C16 straight or branched chain alkyl such that R and R are not simultaneously the same; and m, o, x and y are selected such that the molecule has an overall molecular weight of from about 200 to about 10,000,000, and m, o, x, and y are each selected from zero or greater integers such that m and o are not simultaneously zero, and z is independently selected from 1 or Larger integer. It is recognized that positional isomers of these copolyols are available. The above chemical representation of the R2 moiety containing the R3 and R4 groups is not limiting, but is shown for convenience.
上一段落中结构中示出的聚硅氧烷表面活性剂也可以使用,其中R2为-(CH2)n-O-R5,其中R5为阳离子、阴离子、两性的或两性离子的部分,虽然它不被严格的分类为二甲聚硅氧烷共聚多元醇。The silicone surfactants shown in the structure in the previous paragraph, where R2 is -( CH2 ) n - OR5 , where R5 is a cationic, anionic, amphoteric or zwitterionic moiety, may also be used, although It is not strictly classified as a dimethicone copolyol.
这里用做乳化剂的二甲聚硅氧烷共聚多元醇和其它聚硅氧烷表面活性剂的非限制实例包括:具有聚环氧乙烷侧链的聚二甲基硅氧烷聚醚共聚物、具有聚环氧丙烷侧链的聚二甲基硅氧烷聚醚共聚物、具有聚环氧乙烷和聚环氧丙烷混合侧链的聚二甲基硅氧烷聚醚共聚物、具有聚氧化(乙烯)(丙烯)混合侧链的聚二甲基硅氧烷聚醚共聚物、具有有机甜菜碱侧链的聚二甲基硅氧烷聚醚共聚物、具有羧酸酯(盐)侧链的聚二甲基硅氧烷聚醚共聚物、具有季铵盐侧链的聚二甲基硅氧烷聚醚共聚物、以及含有C2-C30直链、支链或环状烷基部分侧基的上述共聚物的进一步改性物。这里使用的道康宁公司出售的二甲聚硅氧烷共聚多元醇的实例有DowCorning190、193、Q2-5220、2501蜡、2-5324流体和3225C(后者以与环甲聚硅氧烷混合物的形式出售)。商购的鲸蜡基二甲聚硅氧烷共聚多元醇为与聚甘油基-4异硬脂酸酯(和)月桂酸己酯的混合物,商品为ABILWE-09(购自Goldschmidt)。商购的鲸蜡基二甲聚硅氧烷共聚多元醇也为与月桂酸己酯(和)聚甘油基-3油酸酯(和)鲸蜡基二甲聚硅氧烷的混合物,以商品ABILWS-08出售(也购自Goldschmidt)。二甲聚硅氧烷共聚多元醇的其它非限制性实例还包括月桂基二甲聚硅氧烷共聚多元醇、二甲聚硅氧烷共聚多元醇乙酸酯、二甲聚硅氧烷共聚多元醇己二酸酯、二甲聚硅氧烷共聚多元醇胺、二甲聚硅氧烷共聚多元醇二十二烷酸酯二甲聚硅氧烷共聚多元醇丁醚、二甲聚硅氧烷共聚多元醇羟基硬脂酸酯、二甲聚硅氧烷共聚多元醇异硬脂酸酯、二甲聚硅氧烷共聚多元醇月桂酸酯、二甲聚硅氧烷共聚多元醇甲醚、二甲聚硅氧烷共聚多元醇磷酸酯、和二甲聚硅氧烷共聚多元醇硬脂酸酯。见国际化妆品成分词典,第5版,1993。Non-limiting examples of dimethicone copolyols and other silicone surfactants useful herein as emulsifiers include: Dimethicone polyether copolymers having polyethylene oxide side chains, Polydimethylsiloxane polyether copolymer with polypropylene oxide side chain, polydimethylsiloxane polyether copolymer with polyethylene oxide and polypropylene oxide mixed side chain, (Ethylene)(propylene) mixed side chain polydimethylsiloxane polyether copolymer, polydimethylsiloxane polyether copolymer with organobetaine side chain, carboxylate (salt) side chain Polydimethylsiloxane polyether copolymers, polydimethylsiloxane polyether copolymers with quaternary ammonium salt side chains, and side groups containing C2-C30 linear, branched or cyclic alkyl moieties Further modifications of the above-mentioned copolymers. Examples of dimethicone copolyols sold by Dow Corning for use herein are Dow Corning® 190, 193, Q2-5220, 2501 Wax, 2-5324 Fluid, and 3225C (the latter available as a mixture with cyclomethicone). for sale). Cetyl dimethicone copolyol is commercially available as a mixture with polyglyceryl-4 isostearate (and) hexyl laurate as ABIL (R) WE-09 (available from Goldschmidt). Cetyl dimethicone copolyol is also commercially available as a mixture with hexyl laurate (and) polyglyceryl-3 oleate (and) cetyl dimethicone, sold as ABIL (R) WS-08 is sold (also from Goldschmidt). Other non-limiting examples of dimethicone copolyols include lauryl dimethicone copolyol, dimethicone copolyol acetate, dimethicone copolyol Alcohol Adipate, Dimethicone Copolyol Amine, Dimethicone Copolyol Behenate Dimethicone Copolyol Butyl Ether, Dimethicone Copolyol Hydroxystearate, Dimethicone Copolyol Isostearate, Dimethicone Copolyol Laurate, Dimethicone Copolyol Methyl Ether, Dimethicone Copolyol Methyl Ether, Methicone Copolyol Phosphate, and Dimethicone Copolyol Stearate. See International Cosmetic Ingredient Dictionary, 5th Edition, 1993.
这里采用的二甲聚硅氧烷共聚多元醇乳化剂例如描述于USP 4960764,1990年10月2日授权Figueroa,Jr.等人;欧洲专利EP330369,1989年8月3日公开,属于SanoGueira;G.H.Dahms等人的“聚硅氧烷共聚多元醇提供的新配方可能性”,化妆品及盥洗用品,第110卷,第91-100页,1995年3月;M.E.Carlotti等人的“W/O-S乳液的最优化及酯结构和乳液性能之间的定量关系研究”,分散体科学与技术杂志,13(3),315-336(1992);P.Hameyer的“有机的和有机聚硅氧烷乳化剂在化妆品油包水乳液制剂中的可比性技术研究”,HAPPI 28(4),第8-128页(1991);J.Smid-Korbar等人的“聚硅氧烷表面活性剂在乳液中的有效性和适用性”,ProvisionalCommunication,International Journal of Cosmetic Science,12,135-139(1990);和D.G.Krzysik等人的“用于油包水体系的新聚硅氧烷乳化剂”,药品及化妆品工业,第146(4)卷,第28-81页(1990年4月)。The dimethicone copolyol emulsifiers used here are for example described in USP 4960764, authorized on October 2, 1990 to Figueroa, Jr. et al; European Patent EP330369, published on August 3, 1989, belonging to SanoGueira; G.H. Dahms et al., "New formulation possibilities offered by silicone copolyols", Cosmetics & Toiletries, Vol. 110, pp. 91-100, March 1995; M.E. Carlotti et al., "W/O-S Emulsions The optimization of ester structure and quantitative relationship between emulsion properties", Journal of Dispersion Science and Technology, 13 (3), 315-336 (1992); P. Hameyer's "Organic and organopolysiloxane emulsification Comparable technical study of surfactants in cosmetic water-in-oil emulsion formulations", HAPPI 28 (4), pp. 8-128 (1991); J. Smid-Korbar et al. Effectiveness and Suitability of Cosmetic Science”, Provisional Communication, International Journal of Cosmetic Science, 12, 135-139 (1990); and D.G. Krzysik et al., “New polysiloxane emulsifiers for water-in-oil systems”, Pharmaceuticals and Cosmetic Industry, Vol. 146(4), pp. 28-81 (April 1990).
这里采用的不含硅乳化剂包括各种非离子的和阴离子的乳化剂,如糖酯和多酯,烷氧基化糖酯和多酯、C1-C30脂肪醇的C1-C30脂肪酸酯、C1-C30脂肪醇的C1-C30脂肪酸酯的烷氧基化衍生物、C1-C30脂肪醇的烷氧基化醚、C1-C30脂肪酸的聚甘油基酯、多元醇的C1-C30酯、多元醇的C1-C30醚、磷酸烷基酯、聚氧化烯脂肪醚磷酸酯、脂肪酸酰胺、酰基乳酸酯、皂类及其混合物。其它适用的乳化剂例如描述于McCutcheon的洗涤剂和乳化剂,北美版(1986),Allured出版公司出版;USP 5011681,1991年4月30日授权Ciotti等人;USP 4421769,1983年12月20日授权Dixon等人;和USP 3755560,1973年8月28日授权Dickert等人。Silicone-free emulsifiers used here include various nonionic and anionic emulsifiers, such as sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1-C30 fatty acid esters of C1-C30 fatty alcohols, Alkoxylated derivatives of C1-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fatty alcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 esters of polyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps and mixtures thereof. Other suitable emulsifiers are for example described in McCutcheon's Detergents and Emulsifiers, North American Edition (1986), published by Allured Publishing Company; USP 5011681, issued April 30, 1991 to Ciotti et al; USP 4421769, December 20, 1983 to Dixon et al.; and USP 3,755,560, issued Aug. 28, 1973 to Dickert et al.
这些不含硅乳化剂的非限制性实例包括:聚乙二醇20脱水山梨醇单月桂酸酯(Polysorbate 20)、聚乙二醇5大豆甾醇、Steareth-20、Ceteareth-20、PPG-2甲基葡萄糖醚二硬脂酸酯、Ceteth-10、Polysorbate80、磷酸鲸蜡酯、磷酸钾鲸蜡酯、二乙醇胺磷酸鲸蜡酯、Polysorbate 60、硬脂酸甘油酯、PEG-100硬脂酸酯、聚氧化乙烯20脱水山梨醇三油酸酯(Polysorbate 85)、单月桂酸脱水山梨醇酯、聚氧化乙烯4月桂醚硬脂酸钠、聚甘油基-4异硬脂酸酯、月桂酸己酯、Steareth-20、Ceteareth-20、PPG-2甲基葡萄糖醚二硬脂酸酯、Ceteth-10、二乙醇胺磷酸鲸蜡酯、硬脂酸甘油酯、PEG-100硬脂酸酯及其混合物。Non-limiting examples of these silicone-free emulsifiers include: Polyethylene Glycol 20 Sorbitan Monolaurate (Polysorbate 20), Polyethylene Glycol 5 Soy Sterol, Steareth-20, Ceteareth-20, PPG-2 Methanol Glucose Ether Distearate, Ceteth-10, Polysorbate80, Cetyl Phosphate, Potassium Cetyl Phosphate, Diethanolamine Cetyl Phosphate, Polysorbate 60, Glyceryl Stearate, PEG-100 Stearate, Polyoxyethylene 20 sorbitan trioleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4 isostearate, hexyl laurate , Steareth-20, Ceteareth-20, PPG-2 Methyl Glucose Ether Distearate, Ceteth-10, Diethanolamine Cetyl Phosphate, Glyceryl Stearate, PEG-100 Stearate, and mixtures thereof.
b)水包油乳液b) Oil-in-water emulsion
其它优选的局部用载体包括水包油乳液,它具有连续的水相和分散其中的憎水水不溶相(油相)。合适的包括水包油乳液的载体的实例描述于1991年12月17日授权Turner,D.J.等的US 5073371和US 5073372。以下详细描述尤其优选的水包油乳液,它含有结构性试剂、亲水表面活性剂和水。Other preferred topical carriers include oil-in-water emulsions, which have a continuous aqueous phase and dispersed therein a hydrophobic, water-insoluble phase (oil phase). Examples of suitable carriers including oil-in-water emulsions are described in US 5,073,371 and US 5,073,372, issued December 17, 1991 to Turner, D.J. et al. A particularly preferred oil-in-water emulsion containing a structuring agent, a hydrophilic surfactant and water is described in detail below.
(i)结构性试剂(i) Structured reagents
优选的水包油乳液包含结构性试剂以辅助液晶凝胶网络结构的形成。不受理论束缚,认为结构性试剂助于提供组合物以产生组合物稳定性的流变性能。结构性试剂也可以作为乳化剂或表面活性剂。优选的本发明组合物含组合物重量的约0.5%至约20%,更优选约1%至约10%,再优选约1%至约5%的结构性试剂。Preferred oil-in-water emulsions contain structuring agents to aid in the formation of the liquid crystal gel network structure. Without being bound by theory, it is believed that the structuring agent helps provide the rheology of the composition to produce composition stability. Structuring agents can also act as emulsifiers or surfactants. Preferred compositions of the present invention contain from about 0.5% to about 20%, more preferably from about 1% to about 10%, still more preferably from about 1% to about 5%, by weight of the composition, of a structuring agent.
本发明优选的结构性试剂选自硬脂酸、棕榈酸、十八烷醇、十六烷醇、二十二烷醇、硬脂酸、棕榈酸、平均大约有1-5个环氧乙烷单元的十八烷醇的聚乙二醇醚、平均大约有1-21个环氧乙烷单元的十六烷醇的聚乙二醇以及它们的混合物。本发明优选的结构性试剂选自十八烷醇、十六烷醇、二十二烷醇、平均大约有2个环氧乙烷单元的十八烷醇的聚乙二醇醚(steareth-2)、平均大约有21个环氧乙烷单元的十八烷醇的聚乙二醇醚(steareth-21)、平均大约有2个环氧乙烷单元的十六烷醇的聚乙二醇醚以及它们的混合物。更优选的结构性试剂选自硬脂酸、棕榈酸、十八烷醇、十六烷醇、二十二烷醇、steareth-2、steareth-21以及它们的混合物。Preferred structuring agents of the present invention are selected from the group consisting of stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, an average of about 1-5 ethylene oxide Polyethylene glycol ethers of stearyl alcohol, polyethylene glycols of cetyl alcohol having an average of about 1 to 21 ethylene oxide units, and mixtures thereof. Preferred structuring agents of the present invention are selected from the group consisting of stearyl alcohol, cetyl alcohol, behenyl alcohol, polyethylene glycol ethers (steareth-2) of stearyl alcohol with an average of about 2 ethylene oxide units. ), polyethylene glycol ethers of stearyl alcohol with an average of about 21 ethylene oxide units (steareth-21), polyethylene glycol ethers of cetyl alcohol with an average of about 2 ethylene oxide units and their mixtures. More preferred structuring agents are selected from the group consisting of stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, steareth-2, steareth-21 and mixtures thereof.
(ii)亲水的表面活性剂(ii) Hydrophilic surfactants
优选的水包油乳液含有至少一种含量大约在0.05%~10%之间,优选的是大约在1%~6%之间,更优选大约在1%~3%之间的亲水的表面活性剂,它可以分散在水相中的憎水性物质(按局部用载体重量的百分数计)。该表面活性剂至少要亲水以能够在水中足够地分散。Preferred oil-in-water emulsions contain at least one hydrophilic surface in an amount between about 0.05% and 10%, preferably between about 1% and 6%, more preferably between about 1% and 3%. The active agent, which is a hydrophobic material dispersed in the aqueous phase (as a percentage by weight of the topical carrier). The surfactant must be at least hydrophilic to be sufficiently dispersible in water.
适用的表面活性剂包括大量已知的阳离子的、阴离子、两性离子和两性的表面活性剂中的任何一种。参见,1986年由Allured PublishingCorporation出版的McCutcheon的洗涤剂与乳化剂(北美版);美国专利No.5,011,681;美国专利No.4,421,769;美国专利No.3,755,560。Suitable surfactants include any of a large number of known cationic, anionic, zwitterionic and amphoteric surfactants. See, McCutcheon's Detergents and Emulsifiers (North American Edition), Allured Publishing Corporation, 1986; US Patent No. 5,011,681; US Patent No. 4,421,769; US Patent No. 3,755,560.
选择确切的表面活性剂要根据组合物的PH值和存在的其它成份。The exact choice of surfactant will depend upon the pH of the composition and the presence of other ingredients.
优选的是阳离子表面活性剂,特别是二烷基季铵盐化合物,阳离子表面活性剂的例子在下列文献中都有说明:美国专利No.5,151,209;美国专利No.5,151,210;美国专利No.5,120,532;美国专利No.4,387,090;美国专利No.3,155,591;美国专利No.3,929,678;美国专利No.3,959,461;1979年M.C.Publishing Co.出版公司的McCutcheon的洗涤剂与乳化剂(北美版);1949年Interscience Publishers于纽约出版的Schwartz等人的表面活性剂及其化学与技术。所有这些文献在这里都作为参考。这里有用的阳离子表面活性剂包括有下列分子式的阳离子铵盐: Preferred are cationic surfactants, particularly dialkyl quaternary ammonium salt compounds. Examples of cationic surfactants are described in the following documents: U.S. Patent No. 5,151,209; U.S. Patent No. 5,151,210; U.S. Patent No. 5,120,532; U.S. Patent No. 4,387,090; U.S. Patent No. 3,155,591; U.S. Patent No. 3,929,678; U.S. Patent No. 3,959,461; McCutcheon's Detergent and Emulsifier (North American Edition) by MC Publishing Co. in 1979; Interscience Publishers in New York in 1949 Surfactants and their chemistry and technology published by Schwartz et al. All of these documents are incorporated herein by reference. Cationic surfactants useful herein include cationic ammonium salts having the following formula:
其中,R1是一个含有大约12~30个碳原子的烷基,或者含有大约12~30个碳原子的芳香族的芳基或烷芳基;R2、R3和R4要各自从氢、含有大约1~22个碳原子的烷基或者含有大约12~22个碳原子的芳香族的芳基或烷芳基中选择;X是任何相匹配的阴离子,优选选自氯、溴、碘、乙酸根、磷酸根、硝酸根、硫酸根、甲基硫酸根、乙基硫酸根、甲苯磺酸根、乳酸根、柠檬酸根、乙醇酸根以及它们的混合物。另外,烷基R1、R2、R3和R4也可以含有酯键和/或醚键,或者羟基或氨基取代基(例如,烷基可以含有聚乙二醇和聚丙二醇部分)。Wherein, R 1 is an alkyl group containing about 12 to 30 carbon atoms, or an aromatic aryl or alkaryl group containing about 12 to 30 carbon atoms; R 2 , R 3 and R 4 are each from hydrogen , an alkyl group containing about 1 to 22 carbon atoms or an aromatic aryl or alkaryl group containing about 12 to 22 carbon atoms; X is any matching anion, preferably selected from chlorine, bromine, iodine , acetate, phosphate, nitrate, sulfate, methylsulfate, ethylsulfate, toluenesulfonate, lactate, citrate, glycolate, and mixtures thereof. In addition, the alkyl groups R1 , R2 , R3 and R4 may also contain ester linkages and/or ether linkages, or hydroxyl or amino substituents (for example, the alkyl groups may contain polyethylene glycol and polypropylene glycol moieties).
更优选的是,R1是一个含有大约12~22个碳原子的烷基;R2从H或含有大约1~22个碳原子的烷基中选择;R3和R4从氢、含有大约1~3个碳原子烷基中选取;X则如前所述。More preferably, R1 is an alkyl group containing about 12 to 22 carbon atoms; R2 is selected from H or an alkyl group containing about 1 to 22 carbon atoms; R3 and R4 are selected from hydrogen, containing about 1 to 3 carbon atoms selected from the alkyl group; X is as described above.
最优选的是,R1是一个含有大约12~22个碳原子的烷基;R2、R3和R4从氢、含有大约1~3个碳原子烷基中选择;X则如前所述。Most preferably, R 1 is an alkyl group containing about 12 to 22 carbon atoms; R 2 , R 3 and R 4 are selected from hydrogen, an alkyl group having about 1 to 3 carbon atoms; X is as previously described stated.
作为一个替代的办法,其它有用的阳离子乳化剂包括氨基酰胺,其中上述的结构中R1替换为R5CO-(CH2)n-,其中R5是含有大约12~22个碳原子的烷基,n是大约2~6的一个整数,优选的是大约2~4的一个整数,更优选的是大约2~3的一个整数。非限制性的这些阳离子乳化剂包括硬脂酰胺基丙基氯化磷酸PG-dimonium,二十二烷酰胺基丙基氯化PG-dimonium、硬脂酰胺基丙基乙硫酸(ethosulfate)乙基dimonium,硬脂酰胺基丙基二甲基(十四烷基乙酸)氯化铵,硬脂酰胺基丙基二甲基cetearyl甲苯磺酸铵,硬脂酰胺基丙基二甲基氯化铵、硬脂酰胺基丙基二甲基乳酸铵以及它们的混合物。尤其优选二十二烷酰胺基丙基氯化PG-dimonium。As an alternative, other useful cationic emulsifiers include aminoamides in which R1 is replaced by R5CO- ( CH2 )n- in the above structure, where R5 is an alkane containing about 12 to 22 carbon atoms. n is an integer of about 2-6, preferably an integer of about 2-4, more preferably an integer of about 2-3. Non-limiting such cationic emulsifiers include stearamidopropyl phosphoric acid PG-dimonium chloride, behenyl amidopropyl chloride PG-dimonium, stearamidopropyl ethosulfate ethyl dimonium , stearamidopropyl dimethyl (tetradecyl acetic acid) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium toluenesulfonate, stearamidopropyl dimethyl ammonium chloride, hard Fatty amidopropyl dimethyl ammonium lactate and mixtures thereof. Especially preferred is behenylamidopropyl PG-dimonium chloride.
非限制性的季铵盐阳离子包括选自以下的物质:十六烷基氯化铵、十六烷基溴化铵、十二烷基氯化铵、十二烷基溴化铵、硬脂基氯化铵、硬脂基溴化铵、十六烷基二甲基氯化铵、十六烷基二甲基溴化铵、十二烷基二甲基氯化铵、十二烷基二甲基溴化铵、硬脂基二甲基氯化铵、硬脂基二甲基溴化铵、十六烷基三甲基氯化铵、十六烷基三甲基溴化铵、十二烷基三甲基氯化铵、十二烷基三甲基溴化铵、硬脂基三甲基氯化铵、硬脂基三甲基溴化铵、十二烷基二甲基氯化铵、硬脂基二甲基十六烷基二动物脂基二甲基氯化铵、二-十六烷基氯化铵、二-十六烷基溴化铵、二-十二烷基氯化铵、二-十二烷基溴化铵、二-硬脂基氯化铵、二-硬脂基溴化铵、二-十六烷基甲基氯化铵、二-十六烷基甲基溴化铵、二-十二烷基甲基氯化铵、二-十二烷基甲基溴化铵、二-硬脂基甲基氯化铵、二-硬脂基甲基溴化铵以及它们的混合物。其它的的季铵盐包括那些其中C12-C30烷基碳链是由动物脂脂肪酸或椰油脂肪酸衍生的。其中“动物脂基”一词是指一个由通常含C16~C18范围内的烷基的混合物的动物脂肪酸衍生的烷基(通常是加氢的动物脂肪酸),而“椰油”一词是指由通常含C12-C14的烷基混合物的椰油脂肪酸衍生的一个烷基。由这些动物脂和椰子得到的季铵盐的例子包括二动物脂基二甲基氯化铵,二动物脂基二甲基甲基硫酸铵、二(加氢动物脂基)二甲基氯化铵、二(加氢动物脂)二甲基醋酸铵、二动物脂二甲基磷酸铵、二动物脂二甲基硝酸铵、二(椰油烷基)二甲基氯化铵、二(椰油烷基)二甲基溴化铵、动物脂氯化铵、椰油基氯化铵、硬脂酰胺基丙基酸PG-dimonium、硬脂酰胺基丙基乙硫酸乙基dimonium、硬脂酰胺基丙基二甲基(十四烷基乙酸)氯化铵,硬脂酰胺基丙基二甲基cetearyl甲苯磺酸铵、硬脂酰胺基丙基二甲基氯化铵、硬脂酰胺基丙基二甲基乳酸铵以及它们的混合物。具有酯键的烷基的季铵化合物的实例是二动物脂基氧乙基二甲基氯化铵。Non-limiting quaternary ammonium salt cations include materials selected from the group consisting of cetyl ammonium chloride, cetyl ammonium bromide, lauryl ammonium chloride, lauryl ammonium bromide, stearyl Ammonium Chloride, Stearyl Ammonium Bromide, Cetyl Dimethyl Ammonium Chloride, Cetyl Dimethyl Ammonium Bromide, Lauryl Dimethyl Ammonium Chloride, Lauryl Dimethyl Ammonium Chloride ammonium bromide, stearyl dimethyl ammonium chloride, stearyl dimethyl ammonium bromide, cetyl trimethyl ammonium chloride, cetyl trimethyl ammonium bromide, lauryl Trimethyl ammonium chloride, Trimethyl ammonium lauryl bromide, Trimethyl ammonium stearyl chloride, Trimethyl ammonium stearyl bromide, Dimethyl ammonium lauryl chloride, Stearyl Dimethyl Cetyl Ditallow Dimethyl Ammonium Chloride, Di-Cetyl Ammonium Chloride, Di-Cetyl Ammonium Bromide, Di-Lauryl Ammonium Chloride , Two-dodecyl ammonium bromide, two-stearyl ammonium chloride, two-stearyl ammonium bromide, two-hexadecyl methyl ammonium chloride, two-hexadecyl methyl bromide ammonium chloride, di-dodecylmethylammonium chloride, di-dodecylmethylammonium bromide, di-stearylmethylammonium chloride, di-stearylmethylammonium bromide and their mixture. Other quaternary ammonium salts include those in which the C12-C30 alkyl carbon chain is derived from tallow fatty acid or coconut fatty acid. The term "tallow" refers to an alkyl group derived from tallow fatty acids (usually hydrogenated tallow fatty acids), usually containing a mixture of alkyl groups in the range of C16 to C18, and the term "coconut oil" refers to An alkyl group derived from coconut fatty acids usually containing a C12-C14 alkyl mixture. Examples of quaternary ammonium salts derived from such tallow and coconut include ditallow dimethyl ammonium chloride, ditallow dimethyl ammonium methyl sulfate, di(hydrogenated tallow) dimethyl ammonium chloride Ammonium, Di(Hydrogenated Tallow) Dimethyl Ammonium Acetate, Di-Tallow Dimethyl Ammonium Phosphate, Di-Tallow Dimethyl Ammonium Nitrate, Di(Cocoalkyl) Dimethyl Ammonium Chloride, Di(Coconut) Oleoalkyl) Dimethyl Ammonium Bromide, Tallow Ammonium Chloride, Coco Ammonium Chloride, PG-dimonium Stearamidopropyl Ethyl Sulfate, Stearamide Ammonium propyl dimethyl (tetradecyl acetic acid) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium toluene sulfonate, stearamidopropyl dimethyl ammonium chloride, stearamidopropyl ammonium dimethyl lactate and mixtures thereof. An example of a quaternary ammonium compound having an alkyl group having an ester bond is ditallowyloxyethyldimethylammonium chloride.
更优选的阳离子表面活性剂选自二十二烷酰胺基丙基氯化PG-dimonium、二-十二烷基二甲基氯化铵、二-硬脂基二甲基氯化铵、二-十四烷基二甲基氯化铵、二-十六烷基二甲基氯化铵、二-硬脂基二甲基氯化铵、硬脂酰胺基丙基氯化磷酸PG-dimonium、硬脂酰胺基丙基乙硫酸乙基dimonium、硬脂酰胺基丙基二甲基(十四烷基乙酸)氯化铵,硬脂酰胺基丙基二甲基cetearyl甲苯磺酸铵、硬脂酰胺基丙基二甲基氯化铵、硬脂酰胺基丙基二甲基乳酸铵以及它们的混合物。More preferred cationic surfactants are selected from behenyl amidopropyl chloride PG-dimonium, di-dodecyl dimethyl ammonium chloride, di-stearyl dimethyl ammonium chloride, di- Tetradecyl dimethyl ammonium chloride, di-hexadecyl dimethyl ammonium chloride, di-stearyl dimethyl ammonium chloride, stearamidopropyl phosphoric acid PG-dimonium chloride, hard Fatty amidopropyl ethyl dimonium ethyl sulfate, stearamidopropyl dimethyl (tetradecyl acetic acid) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium toluene sulfonate, stearamidopropyl Propyldimethylammonium chloride, stearamidopropyldimethylammonium lactate and mixtures thereof.
最优选的阳离子表面活性剂选自二十二烷酰胺基丙基氯化PG-dimonium、二-十二烷基二甲基氯化铵、二-硬脂基二甲基氯化铵、二-十四烷基二甲基氯化铵、二-十六烷基二甲基氯化铵及其混合物。The most preferred cationic surfactant is selected from behenyl amidopropyl chloride PG-dimonium, di-dodecyl dimethyl ammonium chloride, di-stearyl dimethyl ammonium chloride, di- Tetradecyldimethylammonium chloride, di-hexadecyldimethylammonium chloride and mixtures thereof.
阳离子表面活性剂与结构性试剂的优选结合是二十二烷酰胺基丙基氯化PG-dimonium和/或二十二烷基醇,其中优选对其比例进行优化以维持或增强物理和化学稳定性,尤其是当这种结合含有离子和/或极性大的溶剂时。这一结合尤其适用于输送防晒剂,如氧化锌和甲氧基肉桂酸辛酯。A preferred combination of cationic surfactant and structuring agent is behenyl amidopropyl PG-dimonium chloride and/or behenyl alcohol, where ratios are preferably optimized to maintain or enhance physical and chemical stability properties, especially when the combination contains ionic and/or highly polar solvents. This combination is especially useful for delivering sunscreens such as zinc oxide and octyl methoxycinnamate.
各种阴离子表面活性剂都适用于本发明。见Laughlin等人的美国专利3929678(1975年12月30日授权)该专利内容已全部列入本文供参考。阴离子表面活性剂的非限制性实例包括烷酰基羟乙磺酸盐和烷基硫酸盐与烷基醚硫酸盐。一般烷酰基羟乙磺酸盐可以式RCO-OCH2CH2SO3M表示,其中R是约10-约30个碳原子的烷基或链烯基,M是水溶性阳离子,如铵、钠、钾及三乙醇胺。这些羟乙磺酸盐的非限制性实例包括选自椰油酰基羟乙磺酸铵、椰油酰基羟乙磺酸钠、月桂酰基羟乙磺酸钠、硬脂酰基羟乙磺酸钠及它们的混合物的烷酰基羟乙磺酸盐。A wide variety of anionic surfactants are suitable for use in the present invention. See US Patent 3,929,678 to Laughlin et al. (issued December 30, 1975) which is incorporated herein by reference in its entirety. Non-limiting examples of anionic surfactants include alkanoyl isethionates and alkyl and alkyl ether sulfates. Generally, alkanoyl isethionate can be represented by the formula RCO-OCH 2 CH 2 SO 3 M, wherein R is an alkyl or alkenyl group with about 10 to about 30 carbon atoms, and M is a water-soluble cation, such as ammonium, sodium , potassium and triethanolamine. Non-limiting examples of these isethionates include ammonium cocoyl isethionate, sodium cocoyl isethionate, sodium lauroyl isethionate, sodium stearyl isethionate, and A mixture of alkanoyl isethionates.
烷基硫酸盐和烷基醚硫酸盐通常可用式ROSO3M和RO(C2H4O)XSO3M表示,式中R是约10-约30个碳原子的烷基或链烯基,x是约1-约10、M是水溶性阳离子如铵、钠、钾及三乙醇胺。另一类适用的阴离子表面活性剂是硫酸与有机物反应产物的水溶性盐,其通式为:Alkyl sulfates and alkyl ether sulfates are generally represented by the formulas ROSO 3 M and RO(C 2 H 4 O) X SO 3 M, where R is an alkyl or alkenyl group of about 10 to about 30 carbon atoms , x is from about 1 to about 10, M is a water-soluble cation such as ammonium, sodium, potassium and triethanolamine. Another class of suitable anionic surfactants is the water-soluble salt of the reaction product of sulfuric acid and organic matter, which has the general formula:
R1-SO3-MR 1 -SO 3 -M
式中R1是选自含约8-约24,优选约10-约16个碳原子直链或支链的饱和脂族烃基,M是阳离子。其它合成的阴离子表面活性剂还包括称为琥珀酰胺酸盐、含约12-约24个碳原子的烯烃磺酸盐及β-烷氧基链烷磺酸盐的一类。这类物质的实例有月桂基硫酸钠和月桂基硫酸铵。In the formula, R is selected from straight or branched saturated aliphatic hydrocarbon groups containing about 8 to about 24, preferably about 10 to about 16 carbon atoms, and M is a cation. Other synthetic anionic surfactants include the class known as succinamates, olefin sulfonates having from about 12 to about 24 carbon atoms, and beta-alkoxyalkane sulfonates. Examples of such materials are sodium lauryl sulfate and ammonium lauryl sulfate.
也适用于本发明的阴离子物质是通常含约8-约24个碳原子,优选约10-约20个碳原子的脂肪酸皂(即碱金属盐,如钠盐或钾盐)。制皂用脂肪酸可从天然来源如从植物或动物中取得的甘油酯(如棕榈油、椰子油、大豆油、蓖麻油、牛脂、猪脂等)中获得。脂肪酸也可由合成方法制得。上面引用的美国专利4557853已对皂类作了较详细的说明。Also suitable for use herein are fatty acid soaps (ie alkali metal salts such as sodium or potassium salts) generally containing from about 8 to about 24 carbon atoms, preferably from about 10 to about 20 carbon atoms. Soap-making fatty acids can be obtained from natural sources such as glycerides obtained from plants or animals (eg, palm oil, coconut oil, soybean oil, castor oil, tallow, lard, etc.). Fatty acids can also be produced synthetically. Soaps are described in more detail in U.S. Patent 4,557,853 cited above.
本发明也可以使用两性和两性离子表面活性剂。能用于本发明组合物的两性和两性离子表面活性剂实例包括那些可概括地称为脂族仲胺和叔胺的衍生物,其中脂基可以是直链或支链,且其中一个脂族取代基含约8-约22个碳原子(优选C8-C18),一个含阴离子水溶性基团,如羧基、磺酸根、硫酸根、磷酸根或膦酸根。其实例是烷基亚氨基乙酸盐及通式为RN[(CH2)mCO2M]2与RNH(CH2)mCO2M的亚氨基二链烷酸盐与氨基链烷酸盐,其中m是1-4,R是C8-C22烷基或链烯基,M是氢、碱金属、碱土金属、铵或烷醇铵。咪唑啉鎓与铵的衍生物也包括在内。适用的两性表面活性剂的具体实例包括3-十二烷基-氨基丙酸钠,3-十二烷基氨基丙烷磺酸钠、N-烷基氨基乙磺酸,如根据美国专利2658072提出的十二烷基胺与羟乙磺酸钠反应制得的N-烷基氨基乙磺酸;N-高级烷基天冬氨酸如根据美国专利2438091制造的,以及如美国专利2528378中所述的以商名“Miranol”销售的产品。其它适用的两性表面活性剂包括磷酸盐,如椰油酰胺基丙基PG-二甲基氯化铵磷酸盐(如从Mona公司商购的MonaquatPTC)。Amphoteric and zwitterionic surfactants can also be used in the present invention. Examples of amphoteric and zwitterionic surfactants that can be used in the compositions of the present invention include those derivatives that can be broadly referred to as aliphatic secondary and tertiary amines, wherein the aliphatic groups may be straight or branched and one of the aliphatic The substituents contain from about 8 to about 22 carbon atoms (preferably C8-C18), one containing an anionic water-soluble group such as carboxyl, sulfonate, sulfate, phosphate or phosphonate. Examples are alkyliminoacetates and iminodialkanoates and aminoalkanoates of formula RN[(CH 2 ) m CO 2 M] 2 and RNH(CH 2 ) m CO 2 M , wherein m is 1-4, R is C8-C22 alkyl or alkenyl, M is hydrogen, alkali metal, alkaline earth metal, ammonium or alkanolammonium. Derivatives of imidazolinium and ammonium are also included. Specific examples of suitable amphoteric surfactants include sodium 3-dodecyl-alanine, sodium 3-dodecylaminopropane sulfonate, N-alkyl taurine sulfonic acids, as proposed according to U.S. Patent 2,658,072 N-Alkyl taurine prepared by reaction of dodecylamine with sodium isethionate; N-higher alkyl aspartic acid as manufactured according to U.S. Patent 2,438,091 and as described in U.S. Patent 2,528,378 Product marketed under the trade name "Miranol". Other suitable amphoteric surfactants include phosphates, such as cocamidopropyl PG-dimethylammonium chloride phosphate (eg, Monaquat PTC, commercially available from Mona Corporation).
也适用于本发明的两性或两性离子表面活性剂是甜菜碱。甜菜碱的实例包括高级烷基甜菜碱如椰油基二甲基羧甲基甜菜碱,月桂基二甲基羧甲基甜菜碱、月桂基二甲基α羧乙基甜菜碱、鲸蜡基二甲基羧甲基甜菜碱、鲸蜡基二甲基甜菜碱(从Lonza公司购买的Lonzaine 16SP)、月桂基双-(2-羟乙基)羧甲基甜菜碱、硬脂基双-(2-羟丙基)羧甲基甜菜碱、油基二甲基γ-羧丙基甜菜碱、月桂基双-(2-羟丙基)α-羧乙基甜菜碱、椰油基二甲基磺基丙基甜菜碱、硬脂基二甲基磺基丙基甜菜碱、月桂基二甲基磺基乙基甜菜碱、月桂基双-(2-羟乙基)磺基丙基甜菜碱以及酰胺基甜菜碱与酰胺基磺基甜菜碱(其中RCONH(CH2)3基团连接到甜菜碱的氮原子上)、油基甜菜碱(从Henkel公司购买的两性VelvetexOLB-50)以及椰油酰胺基丙基甜菜碱(从Henkel公司购买的Velvetex BK-35和BA-35)。Amphoteric or zwitterionic surfactants also suitable for use herein are betaines. Examples of betaines include higher alkyl betaines such as cocoyl dimethyl carboxymethyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl dimethyl alpha carboxyethyl betaine, cetyl di Methylcarboxymethylbetaine, cetyldimethylbetaine (Lonzaine 16SP from Lonza), laurylbis-(2-hydroxyethyl)carboxymethylbetaine, stearylbis-(2 -Hydroxypropyl) carboxymethyl betaine, oleyl dimethyl γ-carboxypropyl betaine, lauryl bis-(2-hydroxypropyl) α-carboxyethyl betaine, coco dimethyl sulfonate propyl betaine, stearyl dimethyl sulfopropyl betaine, lauryl dimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl) sulfopropyl betaine and amides betaine and amidosulfobetaine (wherein the RCONH(CH 2 ) 3 group is attached to the nitrogen atom of the betaine), oleyl betaine (VelvetexOLB-50 from Henkel) and cocamido Propyl betaine (Velvetex BK-35 and BA-35 available from Henkel).
其它适用的两性和两性离子表面活性剂包括磺基甜菜碱(sultaine)和羟基磺基甜菜碱,如椰油酰胺基丙基羟基磺基甜菜碱(从Phone-Poulenc公司购买的MiratainCBS)及对应于式RCON(CH3)CH2CH2CO2M的链烷酰基N-甲基甘氨酸盐,其中R是约10-约20个碳原子的烷基或链烯基,M是水溶性阳离子,如铵、钠、钾和三烷醇胺(如三乙醇胺),优选的实例是月桂酰基N-甲基甘氨酸钠。Other suitable amphoteric and zwitterionic surfactants include sultaines and hydroxysultaines such as cocamidopropyl hydroxysultaine (Miratain CBS purchased from Phone-Poulenc) and the corresponding Alkanoyl N-methylglycine salts of the formula RCON(CH 3 )CH 2 CH 2 CO 2 M, wherein R is an alkyl or alkenyl group of about 10 to about 20 carbon atoms, and M is a water-soluble cation, such as Ammonium, sodium, potassium and trialkanolamines such as triethanolamine, a preferred example being sodium lauroyl N-methylglycinate.
(iii)水(iii) water
优选的水包油乳液本发明的组合物含有大约25%~98%、优选的是大约65%~95%、更优选的是大约70%~90%的水,按局部用载体重量计。Preferred Oil-in-Water Emulsions The compositions of the present invention contain from about 25% to 98%, preferably from about 65% to 95%, more preferably from about 70% to 90%, by weight of the topical carrier, of water.
憎水相分散于连续的水相中。憎水相可含水不溶性或部分地水溶性物质,如本领域已知的包括但不限于这里参照水包聚硅氧烷乳液中描述的聚硅氧烷和参照乳液在上面描述的其它油和脂类。The hydrophobic phase is dispersed in the continuous aqueous phase. The hydrophobic phase may contain water insoluble or partially water soluble materials as known in the art including, but not limited to, the silicones described herein with reference to silicone-in-water emulsions and other oils and fats described above with reference to emulsions kind.
本发明的局部用组合物(包括但不限于水剂和乳膏形式)可含有一种皮肤学上可接受的软化剂。这样的组合物优选的是含有约2%到约50%的软化剂。这里使用的“软化剂”是指用于防止或减轻皮肤干燥,同时也保护皮肤的物质。已知有很多种合适的软化剂可以在此使用。在Sagarin,化妆品科学与技术,第二版,Vol.1.pp.32-43(1972)中介绍了很多适合作为软化剂的物质的实施例。优选的软化剂是甘油。甘油的用量为约0.001至约20%,更优选约0.01至10%,再优选约0.1至约5%,例如3%。The topical compositions of the present invention, including but not limited to lotion and cream forms, may contain a dermatologically acceptable emollient. Such compositions preferably contain from about 2% to about 50% softener. As used herein, "emollients" refer to substances that are used to prevent or reduce dryness of the skin while also protecting the skin. A wide variety of suitable softeners are known for use herein. Many examples of substances suitable as emollients are described in Sagarin, Cosmetic Science and Technology, 2nd Edition, Vol. 1. pp. 32-43 (1972). A preferred emollient is glycerin. Glycerin is used in an amount of about 0.001 to about 20%, more preferably about 0.01 to 10%, still more preferably about 0.1 to about 5%, for example 3%.
根据本发明的水剂和乳膏通常含有一个溶液载体体系和一种或多种软化剂。水剂典型的是含约1%到约20%,优选的是约5%到约10%的软化剂;约50%到约90%,优选的是约60%到约80%的水;和上述用量的所述黄嘌呤化合物。乳膏通常含约5%至约50%,优选约10%至约20%的软化剂;约45%至约85%,优选约50%至约75%的水;和上述用量的所述黄嘌呤化合物。Lotions and creams according to the invention generally contain a solution carrier system and one or more emollients. Aqueous formulations typically contain from about 1% to about 20%, preferably from about 5% to about 10%, emollients; from about 50% to about 90%, preferably from about 60% to about 80%, of water; and Said xanthine compound of above-mentioned consumption. Creams generally contain from about 5% to about 50%, preferably from about 10% to about 20%, of an emollient; from about 45% to about 85%, preferably from about 50% to about 75%, of water; Purine compounds.
根据本发明的油膏可含有一种普通的动物或植物油或半固体烃(油质的)载体基质;可吸收水来形成乳液的吸收油膏基质;或水溶性载体,如水溶性溶液载体。油膏还含有增稠剂,如Sagarin,化妆品科学与技术,第二版,Vol.1.pp.72-73(1972)中描述的增稠剂;与/或软化剂。例如,油膏可含有约2%到约10%的软化剂;约0.1%到约2%的增稠剂;及上述用量的所述黄嘌呤化合物。Ointments according to the invention may contain a common animal or vegetable oil or semisolid hydrocarbon (oleaginous) carrier base; absorbent ointment bases which can absorb water to form emulsions; or water-soluble carriers, such as water-soluble solution carriers. Ointments also contain thickeners, such as those described in Sagarin, Cosmetic Science and Technology, Second Edition, Vol. 1.pp.72-73 (1972); and/or emollients. For example, an ointment may contain from about 2% to about 10% of an emollient; from about 0.1% to about 2% of a thickening agent; and the xanthine compound in the above amounts.
本发明的用于清洗的组合物(“清洗剂”)配方中有合适的载体,例如象上面所描述的,优选的是组合物中除含有上述用量的所述黄嘌呤化合物,还含有约1%到约90%,更优选的是约5%到约10%的皮肤学上可接受的表面活性剂。合适的表面活性剂选自阴离子,非离子,两性离子,两性(amphoteric)和两性(ampholytic)表面活性剂,以及这些表面活性剂的混合物。这样的表面活性剂对于洗涤技术的技术人员来说是十分熟知的。可能的表面活性剂的非限制性实施例包括isoceteth-20,甲基椰油酰基牛磺酸钠,甲基油酰牛磺酸钠,和月桂基硫酸钠。1989年1月24日授权Kowez等人的U.S.P.No 4,800,197中介绍了在这里可使用的表面活性剂的实施例,本文在此被完全引用作为参考。Allured出版公司出版的McCutcheon的洗涤剂和乳化剂北美版(1986)中描述了更多种类的在这里可使用的其它表面活性剂的实施例。可选择的是,清洗组合物可含有在清洗组合物中常使用的其它物质,这些物质的用量在其技术已确定的标准上。There are suitable carriers in the composition ("cleaning agent") formulation for cleaning of the present invention, for example as described above, it is preferred that in the composition except containing the described xanthine compound of above-mentioned consumption, also contain about 1 % to about 90%, more preferably about 5% to about 10%, of a dermatologically acceptable surfactant. Suitable surfactants are selected from anionic, nonionic, zwitterionic, amphoteric and ampholytic surfactants, and mixtures of these surfactants. Such surfactants are well known to those skilled in the laundry art. Non-limiting examples of possible surfactants include isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, and sodium lauryl sulfate. Examples of surfactants useful herein are described in U.S.P. No. 4,800,197, issued January 24, 1989 to Kowez et al., which is incorporated herein by reference in its entirety. A wider variety of examples of other surfactants that may be used herein are described in McCutcheon's Detergents and Emulsifiers North American Edition (1986), Allured Publishing Company. Optionally, the cleaning composition may contain other materials conventionally used in cleaning compositions in amounts established in the art.
清洗组合物的物理形态并不关键。组合物可以是,例如香皂条,浴液,香波,洗浴凝胶,头发调理剂,头发滋养剂,膏剂,或摩丝。香皂条是最优选的,因为这是清洗剂最常采用清洗皮肤的形式。漂洗型的清洗组合物,如香波需要一个传输系统来使足够量的活性组分附着在皮肤和头皮上。优选的传输系统涉及到不溶性复合物的使用。要了解这样的传输系统的更完全的公开内容,见1989年5月30日授权Barford等人的U.S.P.4,835,148。The physical form of the cleaning composition is not critical. The composition can be, for example, a soap bar, body wash, shampoo, shower gel, hair conditioner, hair tonic, ointment, or mousse. Toilet bars are most preferred since this is the form in which cleansers are most commonly used to cleanse the skin. Rinse-off cleansing compositions, such as shampoos, require a delivery system to deposit a sufficient amount of active ingredients on the skin and scalp. A preferred delivery system involves the use of insoluble complexes. For a more complete disclosure of such delivery systems, see U.S.P. 4,835,148, issued May 30, 1989 to Barford et al.
这里使用的术语“粉底”指液体,半液体,半固体,或固体皮肤化妆品,其中包括水剂,乳膏,凝胶,糊剂,粉饼,以及类似物质,但并不仅限于此。典型的是粉底在大面积的皮肤上使用,例如在面部,提供特别的外观。粉底典型地是为有色化妆品,如胭脂,腮红,扑面粉以及类似物质提供一个粘附基底,有助于掩盖皮肤缺陷,为皮肤提供一个光滑,平坦的外观。本发明的粉底包含一种皮肤学上可接受的用于所述黄嘌呤化合物的载体,而且也包含常用组分,如油,着色剂,色料,软化剂,香料,蜡,稳定剂,以及类似物质。例如,在以Marcia L.Canter、Brain D.Barford和Brian D.Hofrichter的名义于1995年4月28日提交的共同待审美国专利申请No.08/430,961和1993年1月23日公开的英国专利申请GB 2274585-A中描述一些举例的载体和在此适用的其它组分。pHThe term "foundation" as used herein refers to liquid, semi-liquid, semi-solid, or solid skin cosmetics, including, but not limited to, lotions, creams, gels, pastes, compacts, and the like. Typically foundations are applied over large areas of skin, such as the face, to provide a particular look. Foundations are typically used to provide an adherent base for colored cosmetics, such as blush, blusher, face powder and the like, to help conceal skin imperfections and provide the skin with a smooth, even appearance. The foundation of the present invention comprises a dermatologically acceptable carrier for said xanthine compound, and also comprises usual ingredients such as oils, colorants, pigments, emollients, fragrances, waxes, stabilizers, and Similar substances. For example, in co-pending U.S. Patent Application No. 08/430,961, filed April 28, 1995, in the names of Marcia L. Canter, Brain D. Barford, and Brian D. Hofrichter, and published in the United Kingdom on January 23, 1993 Some exemplary carriers and other components suitable for use herein are described in patent application GB 2274585-A. pH
本发明组合物优选体现约4至约10的pH。更优选地pH为约4.5至9.5,再优选约5至9,最优选约7至9。在再优选的实施方案中,pH为约4至约6或约8至10,更优选为约5至约6或约8至约9。不受理论限制,认为这种规定的pH有助于本发明组合物的黄嘌呤化合物透过哺乳动物皮肤、毛发、或指甲。这种透过作用是由于在黄嘌呤分子上的电荷分布产生的,从而使之更容易穿过。另外,较高的pH值使得整个皮肤的穿透途径的改变是可能的(例如,在角质层中脂质分布和蛋白质相互作用),从而使黄嘌呤分子更多的透过。The compositions of the present invention preferably exhibit a pH of from about 4 to about 10. More preferably the pH is from about 4.5 to 9.5, still more preferably from about 5 to 9, most preferably from about 7 to 9. In yet more preferred embodiments, the pH is from about 4 to about 6 or from about 8 to 10, more preferably from about 5 to about 6 or from about 8 to about 9. Without being bound by theory, it is believed that this defined pH facilitates the penetration of the xanthine compounds of the compositions of the present invention through mammalian skin, hair, or nails. This penetration is due to the charge distribution on the xanthine molecule, making it easier to pass through. In addition, the higher pH makes possible changes in the penetration pathways throughout the skin (for example, lipid distribution and protein interactions in the stratum corneum), allowing greater penetration of xanthine molecules.
任选组分optional components
本发明组合物可包含多种其它成分,如给定产品形式中常使用的那些,只要它们不会不能接受地改变本发明的效果。The compositions of the present invention may contain a variety of other ingredients, such as those commonly used in a given product form, so long as they do not unacceptably alter the effectiveness of the present invention.
在优选的实施方案中,当组合物将与人的皮肤接触时,这些任选组分应适用于皮肤,即当它们引入组合物中时,它们适宜与人的皮肤接触而无合理的医学判断范围内的不当的毒性、不相容性、不稳定性、变性反应等。CTFA化妆品成分手册,第2版(1992)描述了多种常用于护肤工业的非限制性化妆品及药物成分,它们适用于本发明组合物。这些成分类的实例包括:磨料、吸收剂、美观组分如香料、颜料、着色剂、精油、皮肤增感剂(skin sensate)、收敛剂等(如丁子香油、薄荷醇、樟脑、桉树油、丁子香酚、乳酸薄荷醇酯、金缕梅馏出物)、抗痤疮剂、抗结块剂、防泡剂、抗微生物剂(如丁基氨基甲酸碘代丙酯)、抗氧化剂、粘结剂、生物添加剂、缓冲剂、增量剂、螯合剂、化学添加剂、色料、化妆品收敛剂、化妆品杀生剂、变性剂、药物收敛剂、外用止痛剂、成膜剂如有助于组合物的成膜性和亲和性的聚合物(如二十碳烯和乙烯基吡咯烷酮共聚物)、遮光剂、pH调节剂、推进剂、还原剂、多价螯合剂、皮肤增白和增亮剂(如氢醌、曲酸、抗坏血酸、抗坏血酸基磷酸镁、抗坏血酸基葡糖胺)、皮肤调理剂(如湿润剂,包括多种多样的和非闭塞性成分)、皮肤舒适和/或愈合剂(如泛醇和其衍生物如乙基泛醇)、芦荟、泛酸及其衍生物、尿囊素、红没药醇、及甘草酸二钾)、皮肤处理剂、增稠剂、和维生素及其衍生物。In preferred embodiments, when the composition is to come into contact with human skin, these optional components should be suitable for skin application, i.e., they are suitable for contact with human skin when they are incorporated into the composition without sound medical judgment Undue toxicity, incompatibility, instability, denaturation, etc. within the scope. The CTFA Cosmetic Ingredient Handbook, 2nd Edition (1992) describes a wide variety of non-limiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry, which are suitable for use in the compositions of the present invention. Examples of these classes of ingredients include: abrasives, absorbents, aesthetic components such as fragrances, pigments, colorants, essential oils, skin sensates, astringents, etc. (e.g. clove oil, menthol, camphor, eucalyptus, Eugenol, Menthyl Lactate, Witch Hazel Distillate), Anti-Acne Agents, Anti-Caking Agents, Anti-foaming Agents, Antimicrobial Agents (such as Iodopropyl Butylcarbamate), Antioxidants, Adhesives Agents, biological additives, buffers, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, pharmaceutical astringents, external analgesics, film-forming agents such as contributing to the composition Film-forming and substantive polymers (such as eicosene and vinylpyrrolidone copolymers), opacifiers, pH regulators, propellants, reducing agents, sequestrants, skin whitening and lightening agents (such as Hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosamine), skin conditioning agents (such as humectants, including diverse and non-occlusive ingredients), skin comforting and/or healing agents (such as pan alcohol and its derivatives such as ethyl panthenol), aloe, pantothenic acid and its derivatives, allantoin, bisabolol, and dipotassium glycyrrhizinate), skin treatment agents, thickeners, and vitamins and their derivatives.
但是在本发明任何实施方案中,此处使用的活性物可由其设想的作用模式或由其提供的效果来分类。但是,应理解此处的活性物在某些情况下提供多于一种的效果或通过多于一种的作用模式发生作用。因此该分类是为了方便而不是限制活性物为特定的指出的作用。脱皮屑活性物In any embodiment of the invention, however, the actives used herein can be classified by their envisaged mode of action or by the effect they provide. However, it is understood that the actives herein may in some instances provide more than one effect or operate via more than one mode of action. This classification is therefore for convenience and does not limit the active to a specific indicated effect. Desquamation Actives
在本发明的组合物内可以加入安全且有效用量的脱皮屑活性物,更优选的是占组合物重量的约0.1%到约10%,更优选的是约0.2%到约5%,同样优选的是约0.5%到约4%。脱皮屑活性物可增强本发明的改善皮肤外观的优点。例如,脱皮屑活性物有助于改善皮肤质地(如光滑度)。一类适用于此的脱皮屑体系含巯基化合物和两性离子表面活性剂并描述于以Donald L.Bisset的名义于1995年6月7日提交的共同待审申请No.08/480,632,相应于6/29/95提交的PCT申请US 95/0816。另一类适用于此的脱皮屑体系含水杨酸和两性离子表面活性剂,并描述于1995年11月13日提交的共同待审申请08/554,994,它是1994年3月9日提交的08/209,401的继续申请,以Bissett的名义,相应于11/4/94提交、5/18/95公开的PCT申请94/12745。例如这些申请中描述的两性离子表面活性剂也可用作这里的脱皮屑剂,尤其优选鲸蜡基甜菜碱。Safe and effective amounts of desquamation actives may be incorporated into the compositions of the present invention, more preferably from about 0.1% to about 10%, more preferably from about 0.2% to about 5%, by weight of the composition, and also preferably is about 0.5% to about 4%. The skin appearance benefits of the present invention are enhanced by desquamation actives. For example, desquamation actives help improve skin texture (eg, smoothness). A class of desquamation systems useful herein contains mercapto compounds and zwitterionic surfactants and is described in co-pending application No. 08/480,632, filed June 7, 1995, in the name of Donald L. Bisset, corresponding to 6 PCT application US 95/0816 filed on /29/95. Another class of exfoliating systems suitable for use herein contains salicylic acid and zwitterionic surfactants and is described in co-pending application 08/554,994, filed November 13, 1995, which was filed on March 9, 1994. Continuation of /209,401, in the name of Bissett, corresponding to PCT Application 94/12745 filed 11/4/94 and published 5/18/95. Zwitterionic surfactants such as those described in these applications are also useful as desquamation agents herein, cetyl betaine being especially preferred.
抗痤疮活性物anti-acne actives
本发明组合物可包含安全有效量的一种或多种抗痤疮活性物。适用的抗痤疮活性物的例子有间苯二酚、硫黄、水杨酸、红霉素、锌等。其它适用的抗痤疮活性物的实例描述于1997年3月4日授权McAtee等人的USP5607980。The compositions of the present invention may contain a safe and effective amount of one or more anti-acne actives. Examples of suitable anti-acne actives are resorcinol, sulfur, salicylic acid, erythromycin, zinc and the like. Examples of other suitable anti-acne actives are described in USP 5,607,980, issued March 4, 1997 to McAtee et al.
抗皱纹活性物/抗萎缩活性物Anti-Wrinkle Actives/Anti-Atrophy Actives
本发明组合物可还包含安全有效量的一种或多种抗皱纹或抗萎缩活性物。这里适用的该活性物的实例有含硫的D和L氨基酸及其衍生物和盐,尤其是N-乙酰基衍生物,其优选的实例是N-乙酰基-L-半胱氨酸;硫醇,如乙硫醇;羟基醇、植酸、硫辛酸;溶血磷脂酸、脱皮剂(如苯酚等)、维生素B3化合物及类视色素,它们增强本发明的皮肤外观的益处。a)维生素B3化合物The compositions of the present invention may further comprise a safe and effective amount of one or more anti-wrinkle or anti-atrophy actives. Examples of such actives suitable here are sulfur-containing D and L amino acids and their derivatives and salts, especially N-acetyl derivatives, a preferred example of which is N-acetyl-L-cysteine; sulfur Alcohols, such as ethanethiol; hydroxy alcohols, phytic acid, lipoic acid; lysophosphatidic acid, peeling agents (such as phenol, etc.), vitamin B3 compounds and retinoids, which enhance the skin appearance benefits of the present invention. a) Vitamin B3 compound
本发明组合物包含安全和有效量的维生素B3化合物。正如共同待审的US申请No.08/834,010(1997年4月11日申请,对应于国际公开WO97/39733A1,1997年10月30日公开)中描述的,维生素B3化合物尤其适用于调节皮肤状况。当它存在于本发明组合物中时,组合物优选包含其重量的约0.01%至约50%,更优选约0.1%至约10%,更优选约0.5%至约10%,和更优选约1%至约5%,最优选约2%至约5%的维生素B3化合物。The compositions of the present invention comprise a safe and effective amount of a vitamin B3 compound. Vitamin B3 compounds are especially useful for regulating skin situation. When it is present in the compositions of the present invention, the compositions preferably comprise from about 0.01% to about 50%, more preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 10%, and more preferably about 1% to about 5%, most preferably about 2% to about 5%, vitamin B3 compound.
这里的“维生素B3化合物”是指具有下式的化合物: Here "vitamin B3 compound" means a compound having the following formula:
其中R为-CONH2(即烟酰胺)、-COOH(即烟酸)或-CH2OH(即烟醇);其衍生物;和任何上述物质的盐。wherein R is -CONH2 (ie nicotinamide), -COOH (ie nicotinic acid) or -CH2OH (ie nicotinic alcohol); derivatives thereof; and salts of any of the foregoing.
上述维生素B3化合物的举例性衍生物包括烟酸酯,包括烟酸的非血管扩张性酯(如烟酸生育酚酯)、烟基氨基酸、羧酸的烟醇酯、烟酸N-氧化物和烟酰胺N-氧化物。Exemplary derivatives of the aforementioned vitamin B3 compounds include nicotinic acid esters, including non-vasodilatory esters of nicotinic acid (such as tocopheryl nicotinate), nicotinyl amino acids, nicotinol esters of carboxylic acids, nicotinic acid N-oxide and Niacinamide N-oxide.
上述维生素B3化合物的实例是本领域中熟知的,并可购自多种商源,如西格玛化学公司(圣路易斯市,MO),ICN Biomedicals Inc.(Irvin,CA)和Aldrich化学公司(Milwaukee,WI)。Examples of the aforementioned vitamin B3 compounds are well known in the art and are available from various commercial sources such as Sigma Chemical Company (St. Louis, MO), ICN Biomedicals Inc. (Irvin, CA) and Aldrich Chemical Company (Milwaukee, CA). WI).
优选维生素B3化合物是烟酰胺。A preferred vitamin B3 compound is niacinamide.
包括的维生素B3化合物可以是基本上纯物质,或是从天然源(如植物)的适当物理和化学分离获得的提取物。b)类视色素Vitamin B3 compounds may be included as substantially pure material, or as extracts obtained by suitable physical and chemical isolation from natural sources such as plants. b) Retinoids
本发明组合物可以包含类视色素,除非另有说明。这里采用的“类视色素”包括维生素A或视黄醇类化合物的所有天然和/或合成的维生素A的同类物,它们在皮肤内具有维生素A的生物活性,以及这些化合物的几何异构体和立体异构体。类视色素优选为视黄醇、视黄醇酯(如视黄醇的C2-C22烷基酯、包括棕榈酸视黄醇酯、乙酸视黄醇酯、丙酸视黄醇酯)、视黄醛、和/或视黄酸(包括全反式视黄酸和/或13-顺视黄酸),更优选除视黄酸外的类视色素。这些化合物是本领域中熟知的并可商购自各种来源,如西格玛化学公司(圣路易斯,MO),和Boerhinger Mannheim(Indianapolis,IN)。这里采用的其它类视色素描述于USP 4677120,1987年6月30日授权Parish等人;4885311,1989年12月5日授权Parish等人;5049584,1991年9月17日授权Purcell等人;5124356,1992年6月23日授权Purcell等人;和Reissue 34075,1992年9月22日授权Purcell等人。其它适用的类视色素为视黄酸生育酚酯[(顺或反)视黄酸生育酚酯、adapalene{6-[3-(1-金刚烷基)-4-甲氧基苯基]-2-萘甲酸}和tazarotene(6-[2-(4,4-二甲基硫代苯并二氢吡喃-6-基)-乙炔基]烟酸乙酯)。优选的类视色素为视黄醇、棕榈酸视黄醇酯、乙酸视黄醇酯、丙酸视黄醇酯、视黄醛及其结合。Compositions of the present invention may contain a retinoid unless otherwise indicated. As used herein, "retinoids" include all natural and/or synthetic congeners of vitamin A or retinol-like compounds that possess the biological activity of vitamin A in the skin, as well as geometric isomers of these compounds and stereoisomers. Retinoids are preferably retinol, retinyl esters (such as C2-C22 alkyl esters of retinol, including retinyl palmitate, retinyl acetate, retinyl propionate), retinyl Aldehydes, and/or retinoic acid (including all-trans retinoic acid and/or 13-cis retinoic acid), more preferably retinoids other than retinoic acid. These compounds are well known in the art and are commercially available from various sources such as Sigma Chemical Company (St. Louis, MO), and Boerhinger Mannheim (Indianapolis, IN). Other retinoids employed herein are described in USP 4677120, issued June 30, 1987 to Parish et al; 4885311, issued December 5, 1989 to Parish et al; 5049584, issued September 17, 1991 to Purcell et al; , authorized June 23, 1992 to Purcell et al; and Reissue 34075, issued September 22, 1992 to Purcell et al. Other suitable retinoids are tocopheryl retinoate [(cis or trans) tocopheryl retinoate, adapalene {6-[3-(1-adamantyl)-4-methoxyphenyl]- 2-naphthoic acid} and tazarotene (ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate). Preferred retinoids are retinol, retinyl palmitate, retinyl acetate, retinyl propionate, retinal and combinations thereof.
类视色素可以以基本上纯的物质,或以从天然(如植物)源进行适当物理和/或化学分离获得的提取物形式使用。优选类视色素为基本上纯的,更优选为本质上纯的。Retinoids may be used as substantially pure material, or as extracts obtained by suitable physical and/or chemical isolation from natural (eg, plant) sources. Preferably the retinoid is substantially pure, more preferably essentially pure.
本发明的组合物优选可以含有安全及有效量的类视色素,使得所得的组合物对于调节角质组织,优选对于调节可见的和/或可触觉的皮肤质地不连续性是安全和有效的。组合物优选含约0.005%至约2%,更优选0.01%至约2%的类视色素。视黄醇优选的用量是约0.01%至约0.15%;视黄醇酯优选的用量为约0.01%至约2%(如约1%);视黄酸最优选的用量为约0.01%至约0.25%;视黄酸生育酚酯,adapalene,和tazarotene最优选的用量为约0.01%至约2%。The compositions of the present invention may preferably contain a safe and effective amount of retinoid such that the resulting composition is safe and effective for regulating keratinous tissue, preferably for regulating visible and/or tactile discontinuities in skin texture. The compositions preferably contain from about 0.005% to about 2%, more preferably from 0.01% to about 2%, of a retinoid. Retinol is preferably used in an amount of about 0.01% to about 0.15%; retinol esters are used in a preferred amount of about 0.01% to about 2% (eg, about 1%); %; Tocopheryl retinoate, adapalene, and tazarotene are most preferably used in amounts of about 0.01% to about 2%.
当本发明组合物既包含类视色素也包含维生素B3化合物,类视色素优选按以上描述的用量使用,维生素B3化合物的优选用量为约0.1%至约10%,更优选约2%至约5%。抗氧化剂/游离基清除剂When the compositions of the present invention contain both retinoids and vitamin B3 compounds, the retinoids are preferably used in the amounts described above, and the vitamin B3 compounds are preferably used in an amount of from about 0.1% to about 10%, more preferably from about 2% to about 5%. Antioxidant/Free Radical Scavenger
本发明组合物可包含安全有效量的抗氧化剂/游离基清除剂。抗氧化剂/游离基清除剂尤其具有防止紫外线侵害和其它环境因素对皮肤的损伤的作用,紫外线可导致鳞片增加或角质层组织变化。The compositions of the present invention may contain a safe and effective amount of an antioxidant/radical scavenger. Antioxidants/radical scavengers are especially useful in protecting the skin from UV rays and other environmental factors that can cause increased scaling or changes in the texture of the stratum corneum.
在本发明的组合物内加入安全且有效用量的抗氧化剂/游离基清除剂,优选的是占组合物的约0.1%到约10%,更优选的是约1%到约5%。Antioxidants/radical scavengers are included in the compositions of the present invention in safe and effective amounts, preferably from about 0.1% to about 10%, more preferably from about 1% to about 5%, of the composition.
可使用的抗氧化剂/游离基清除剂是,如抗坏血酸(维生素C)及其盐,脂肪酸的抗坏血酸酯,抗坏血酸衍生物(如抗坏血酸磷酸镁),生育酚(维生素E),山梨酸生育酚酯,乙酸生育酚酯,生育酚的其它酯,丁基化的羟基苯甲酸及其盐,6-羟基-2,5,7,8-四甲基苯并二氢吡喃-2-羧酸(市售商品的品名为Trolox,棓酸及其烷基酯,特别是棓酸丙酯,尿酸及其盐和烷基酯,山梨酸及其盐,胺(如N,N-二乙基羟基胺,氨基胍),巯基化合物(如谷胱甘肽)和二羟基富马酸及其盐,枸杞碱pidolate、精氨酸pidolate、去甲二氢愈创木酸、生物类黄酮、赖氨酸、甲硫氨酸、脯氨酸、超氧物岐化酶、水飞蓟素、茶提取物、葡萄皮/籽提取物、黑素和迷迭香提取物。优选的抗氧化剂/游离基清除剂选自山梨酸生育酚酯和生育酚的其它酯,更优选山梨酸生育酚酯。例如,1989年7月11日授权DonaldL.Bissett,Rodney D.Bush和Ranjit Chatterjee的U.S.P.No.4,847,071中描述了在局部用组合物中使用和适用于本发明的山梨酸生育酚酯。螯合剂Antioxidants/radical scavengers that can be used are, for example, ascorbic acid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (such as magnesium ascorbyl phosphate), tocopherol (vitamin E), tocopheryl sorbate, Tocopheryl acetate, other esters of tocopherol, butylated hydroxybenzoic acid and its salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (market Commercially available under the name Trolox® , gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, amines (such as N,N-diethylhydroxylamine , aminoguanidine), sulfhydryl compounds (such as glutathione) and dihydroxyfumaric acid and its salts, lycine pidolate, arginine pidolate, nordihydroguaiaretic acid, bioflavonoids, lysine, Methionine, Proline, Superoxide Dismutase, Silymarin, Tea Extract, Grape Skin/Seed Extract, Melanin and Rosemary Extract. Preferred antioxidant/radical scavenger is selected from Sorbus Tocopheryl acid and other esters of tocopherol, more preferably tocopheryl sorbate. For example, USP No. 4,847,071 issued Jul. 11, 1989 to Donald L. Bissett, Rodney D. Bush and Ranjit Chatterjee describes the topical combination Tocopheryl sorbate used in and suitable for use in the present invention. Chelating agent
本发明组合物可以包含安全有效量的螯合剂或螯合试剂。这里使用的“螯合剂”或“螯合试剂”意为能通过形成配合物来从体系中去除金属离子的活性试剂,这样金属离子就不会轻易地参与或催化化学反应。螯合试剂的加入尤其具有防止紫外线侵害和其它环境因素对皮肤损伤的作用,紫外线可导致过多鳞片或皮肤组织变化。The compositions of the present invention may contain a safe and effective amount of a chelating agent or chelating agent. As used herein, "chelating agent" or "chelating agent" means an active agent capable of removing metal ions from a system by forming complexes so that the metal ions cannot readily participate in or catalyze chemical reactions. The addition of chelating agents is particularly effective in preventing skin damage from UV rays and other environmental factors that can cause excessive scaling or changes in skin tissue.
在本发明的组合物内加入安全且有效用量的螯合试剂,优选的是占组合物的约0.1%到约10%,更优选的是约1%到约5%。在此可用的典型的螯合剂公开在Bissett等的USP 5487884,授权日1/30/96;Bush等的国际申请公开91/16035,公开日10/31/95;和Bush等的国际申请公开91/16034,公开日10/31/95。本发明的组合物中使用的螯合剂优选的是糠偶酰二肟及其衍生物。The chelating agent is included in the compositions of the present invention in a safe and effective amount, preferably from about 0.1% to about 10%, more preferably from about 1% to about 5%, of the composition. Typical chelating agents useful herein are disclosed in USP 5487884, issued 1/30/96 to Bissett et al; International Application Publication 91/16035, published 10/31/95 to Bush et al; and International Application Publication 91 to Bush et al. /16034, open date 10/31/95. The chelating agent used in the composition of the present invention is preferably furildioxime and its derivatives.
类黄酮flavonoids
本发明组合物可任选地含有类黄酮化合物。类黄酮广泛公开于US5686082和5686367中。适用于本发明的类黄酮是黄烷酮,选自未取代的黄烷酮、单取代的黄烷酮及其混合物;查耳酮,选自未取代的查耳酮、单取代的、二取代的、和三取代的查耳酮及其混合物;黄酮,选自未取代的黄酮、单取代的、和二取代的黄酮、及其混合物;一种或多种异黄酮;香豆素,选自未取代的香豆素、单取代的、和二取代的香豆素、及其混合物;色酮,选自未取代的色酮、单取代的、和二取代的色酮、及其混合物;一种或多种败坏翘摇素;一种或多种苯并二氢吡喃-4-酮;一种或多种苯并二氢吡喃醇(chromanol);其异构体(如顺/反异构体);及其混合物。术语“取代的”在此是指类黄酮的一个或多个氢原子已被羟基、C1-C8烷基、C1-C4烷氧基、O-糖苷等及这些取代基的混合物独立地取代的类黄酮。Compositions of the present invention may optionally contain flavonoid compounds. Flavonoids are widely disclosed in US5686082 and 5686367. Flavonoids suitable for use in the present invention are flavanones selected from unsubstituted flavanones, monosubstituted flavanones and mixtures thereof; chalcones selected from unsubstituted chalcones, monosubstituted, disubstituted and trisubstituted chalcones and mixtures thereof; flavones selected from unsubstituted flavones, monosubstituted and disubstituted flavones, and mixtures thereof; one or more isoflavones; coumarins selected from Unsubstituted coumarins, monosubstituted, and disubstituted coumarins, and mixtures thereof; chromones selected from unsubstituted chromones, monosubstituted, and disubstituted chromones, and mixtures thereof; One or more sputum; One or more chroman-4-ones; One or more chromanols (chromanol); Its isomers (such as cis/trans isomers); and mixtures thereof. The term "substituted" herein refers to flavonoids in which one or more hydrogen atoms have been independently substituted by hydroxyl, C1-C8 alkyl, C1-C4 alkoxy, O-glycoside, etc., and mixtures of these substituents. flavonoids.
适合的类黄酮的实例包括但不限于未取代的黄烷酮、单羟基黄烷酮(如2’-羟基黄烷酮、6-羟基黄烷酮、7-羟基黄烷酮等)、单烷氧基黄烷酮(如5-甲氧基黄烷酮、6-甲氧基黄烷酮、7-甲氧基黄烷酮、4’-甲氧基黄烷酮等)、未取代的查耳酮(尤其是未取代的反式查耳酮)、单羟基查耳酮(如2’-羟基查耳酮、4’-羟基查耳酮等)、二羟基查耳酮(如2’,4-二羟基查耳酮、2’,4’-二羟基查耳酮、2,2’-二羟基查耳酮、2’,3-二羟基查耳酮、2’,5’-二羟基查耳酮等)、和三羟基查耳酮(如2’,3’,4’-三羟基查耳酮、4,2’,4’-三羟基查耳酮、2,2’,4’-三羟基查耳酮等)、未取代的黄酮、7,2’-二羟基黄酮、3’,4’-二羟基萘黄酮、4’-羟基黄酮、5,6-苯并黄酮、和7,8-苯并黄酮、未取代的异黄酮、黄豆苷原(7,4’-二羟基异黄酮)、5,7-二羟基-4’-甲氧基异黄酮、大豆异黄酮(大豆的提取混合物)、未取代的香豆素、4-羟基香豆素、7-羟基香豆素、6-羟基-4-甲基香豆素、未取代的色酮、3-甲酰基色酮、3-甲酰基-6-异丙基色酮、未取代的败坏翘摇素、未取代的苯并二氢吡喃-4-酮、未取代的苯并二氢吡喃-4-醇、及其混合物。Examples of suitable flavonoids include, but are not limited to, unsubstituted flavanones, monohydroxyflavanones (such as 2'-hydroxyflavanones, 6-hydroxyflavanones, 7-hydroxyflavanones, etc.), Oxyflavanone (such as 5-methoxyflavanone, 6-methoxyflavanone, 7-methoxyflavanone, 4'-methoxyflavanone, etc.), unsubstituted chalco Chalcone (especially unsubstituted trans-chalcone), monohydroxychalcone (such as 2'-hydroxychalcone, 4'-hydroxychalcone, etc.), dihydroxychalcone (such as 2', 4-Dihydroxychalcone, 2',4'-Dihydroxychalcone, 2,2'-Dihydroxychalcone, 2',3-Dihydroxychalcone, 2',5'-Dihydroxychalcone Chalcone, etc.), and trihydroxychalcone (such as 2', 3', 4'-trihydroxychalcone, 4,2', 4'-trihydroxychalcone, 2,2', 4' -trihydroxychalcone, etc.), unsubstituted flavones, 7,2'-dihydroxyflavones, 3',4'-dihydroxynaphthoflavones, 4'-hydroxyflavones, 5,6-benzoflavones, and 7 , 8-benzoflavone, unsubstituted isoflavone, daidzein (7,4'-dihydroxyisoflavone), 5,7-dihydroxy-4'-methoxyisoflavone, soybean isoflavone (soybean Extract mixture), unsubstituted coumarin, 4-hydroxycoumarin, 7-hydroxycoumarin, 6-hydroxy-4-methylcoumarin, unsubstituted chromone, 3-formylchromone, 3-formyl-6-isopropyl chromone, unsubstituted romansin, unsubstituted chroman-4-one, unsubstituted chroman-4-ol, and mixture.
这里优选的是香豆素、未取代的黄烷酮、甲氧基黄烷酮、未取代的查耳酮、2’-4二羟基查耳酮、及其混合物。更优选未取代的黄烷酮、未取代的查耳酮(尤其是反式异构体)、及其混合物。Preferred herein are coumarins, unsubstituted flavanones, methoxyflavanones, unsubstituted chalcones, 2'-4 dihydroxychalcones, and mixtures thereof. More preferred are unsubstituted flavanones, unsubstituted chalcones (especially the trans isomer), and mixtures thereof.
它们可以是合成物质或是从天然源(如植物)获取的萃取物。天然源物质还可被衍生(如从天然源提取后制备的酯或醚衍生物)。用于此处的类黄酮化合物有多种来源商购,如Indofine化学公司(Somerville,NewJersey)、Steraloids公司(Wilton,New Hampshire)和Aldrich化学公司(Milwaukee,Wisconsin)。They can be synthetic substances or extracts obtained from natural sources such as plants. Natural source materials may also be derivatized (eg, ester or ether derivatives prepared after extraction from natural sources). Flavonoid compounds useful herein are commercially available from a variety of sources, such as Indofine Chemical Company (Somerville, New Jersey), Steraloids Company (Wilton, New Hampshire), and Aldrich Chemical Company (Milwaukee, Wisconsin).
也可以使用上述类黄酮化合物的混合物。Mixtures of the above flavonoid compounds may also be used.
这里描述的类黄酮化合物在本发明中的优选浓度为约0.01%至约20%,更优选约0.1%至约10%,最优选约0.5%至约5%。抗炎症试剂Preferred concentrations of the flavonoid compounds described herein in the present invention are from about 0.01% to about 20%, more preferably from about 0.1% to about 10%, most preferably from about 0.5% to about 5%. anti-inflammatory agent
可向本发明的组合物中加入安全且有效用量的抗炎症试剂,优选的是占组合物的约0.1%到约10%,更优选的是约0.5%到约5%。抗炎症试剂可增强本发明的改善皮肤外观的优点,如这样的试剂有助于更均匀和可接受的皮肤色调或颜色。组合物中抗炎症试剂的准确用量取决于使用的具体的抗炎症试剂,因为这类试剂效力变化范围很大。Anti-inflammatory agents can be added to the compositions of the present invention in safe and effective amounts, preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 5%, of the composition. The skin appearance improving benefits of the present invention can be enhanced by anti-inflammatory agents, as such agents contribute to a more even and acceptable skin tone or color. The exact amount of anti-inflammatory agent used in the composition will depend on the particular anti-inflammatory agent used, since the potency of such agents can vary widely.
甾族抗炎剂包括但不限于:皮质类甾醇如氢化可的松、羟基氟羟脱氢皮质(甾)醇、α-甲基地塞米松、磷酸地塞米松、二丙酸氯地米松、戊酸氯氟美松、丙酮缩羟强的松龙、氟二羟基甲基孕甾二烯二酮、醋酸去氧皮甾酮、地塞米松、二氯去氧强的松、双醋二氟松、戊酸二氟米松、fluadrenolone、氟二氯松丙酮化合物、氟氢可的松、三甲基乙酸氟米松、fluosinolone丙酮化合物、肤轻松醋酸酯、二氟美松(flucortine)丁基酯、氟考龙、醋酸氟强的松、丙酮缩氟羟龙、哈西奈德、醋酸氢化可的松、丁酸氢化可的松、甲基氢化泼尼松、曲安西龙丙酮化合物、可的松、可多托松、flucetonide、氢氟可的松、difluorosone diacetate、丙酮缩氟羟龙丙酮化合物、甲羟松、安西法尔、安西非特、倍它米松和其余量的酯、氯强的松、醋酸氯强的松、氯可托龙、clescinolone、二氯去氧的松、醋丁二氟龙、氟二氯松、9-去氟肤轻松、氟米松、醋酸甲氟龙、氟氢化泼尼松、戊酸氢化可的松、氢化可的松环戊丙酸酯、氢可松氨酯、甲泼尼松、帕拉米松、氢化泼尼松、泼尼松、氯地米松二丙酸酯、曲安西龙和其混合物。优选使用的甾族抗炎剂是羟基可的松。Steroidal anti-inflammatory agents include, but are not limited to: corticosteroids such as hydrocortisone, hydroxyfluorocorticosterol, alpha-methyldexamethasone, dexamethasone phosphate, beclomethasone dipropionate, Clomethasone, acetone hydroxyprednisolone, fluorodihydroxymethylpregnanedione, deoxycorticosterone acetate, dexamethasone, dichlordeoxyprednisone, difloxadione , diflumetasone valerate, fluadrenolone, fludromethasone acetonide, fludrocortisone, flumetasone trimethylacetate, fluosinolone acetonide, fluocinolone acetate, flucortine butyl ester, fluocortine Colon, Fludroprednisolone Acetate, Fluoxetal, Halcinonide, Hydrocortisone Acetate, Hydrocortisone Butyrate, Methylprednisolone, Triamcinolone Acetonide, Cortisone, Cortisone Dotosone, flucetonide, hydrocortisone, difluorosone diacetate, acetone fluorescein acetonide, medrison, amcetafal, amcetafel, betamethasone and other amounts of esters, clorprednisone, chloroacetate Prednisone, clocotorolone, clescinolone, diclodextranone, diflunolone acetate, fluorodiclosone, 9-defluocinonide, flumethasone, methylflurone acetate, fluprednisone, Hydrocortisone valerate, hydrocortisone cypionate, hydrocortisone carbamate, methylprednisone, paramethasone, prednisone, prednisone, beclomethasone dipropionate, koji Anthiron and its mixtures. A preferred steroidal anti-inflammatory agent for use is hydroxycortisone.
可用于本发明的第二类抗炎剂包括非甾族抗炎剂。这类抗炎剂包括的化合物是本领域熟练技术人员公知的。对于非甾族抗炎剂的化学结构、合成、副作用等的详细公开,可参考权威著作,包括:抗炎和抗风湿药,K.D.Rainsford,Vol.I-III,CRC出版社,Boca Raton,(1985),和抗炎剂、化学和药物学1,R.A.Scherrer等人,学院出版社,纽约(1974)。A second class of anti-inflammatory agents useful in the present invention includes non-steroidal anti-inflammatory agents. Such anti-inflammatory agents include compounds well known to those skilled in the art. For the detailed disclosure of the chemical structure, synthesis, and side effects of non-steroidal anti-inflammatory agents, you can refer to authoritative works, including: Anti-inflammatory and anti-rheumatic drugs, K.D.Rainsford, Vol.I-III, CRC Press, Boca Raton, ( 1985), and Anti-Inflammatory Agents, Chemistry and Pharmacology 1, R.A. Scherrer et al., Academy Press, New York (1974).
用于本发明组合物中的具体非甾族抗炎剂包括但不限于:Specific non-steroidal anti-inflammatory agents for use in the compositions of the present invention include, but are not limited to:
1)oxicams如吡罗昔康、异噁噻酰胺、替诺昔康、舒多昔康和CP-14,304;1) oxicams such as piroxicam, isoxathiamide, tenoxicam, sudoxicam and CP-14,304;
2)水杨酸酯类如乙酰水杨酸、双水杨酸、贝诺酯、三水杨酸胆碱镁、safaprin、solprin、二氟尼柳和芬度柳;2) Salicylates such as acetylsalicylic acid, disalicylic acid, benoate, choline magnesium trisalicylate, safaprin, solprin, diflunisal and fentusal;
3)乙酸衍生物如二氯苯胺苯乙酸、芬氟酸、消炎痛、舒林酸、托美丁、伊索克酸、乙基二氢并呋喃乙酸、二氢氧二苯并硫杂环庚三烯乙酸、齐多美辛、阿西美辛、芬替酸、佐美酸、环氯茚酸、奥昔平酸和联苯乙酸;3) Acetic acid derivatives such as diclofenac, fenflurmic acid, indomethacin, sulindac, tolmetin, isoket acid, ethyl dihydrofuran acetic acid, dihydrooxydibenzothiepine Trieneacetic acid, zidometacin, acemetacin, fenticic acid, zomeacin, cloindacid, oxipinic acid, and felbinac;
4)灭酸类(fenamates)如甲灭酸、甲氯灭酸、氟灭酸、尼氟灭酸和托灭酸;4) Fenamates such as mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid and trofenamic acid;
5)丙酸衍生物如异丁苯丙酸、甲氧基甲基萘乙酸、苯噁洛芬、氟联苯丙酸、酮丙酸、苯氧苯丙酸、联苯丁酮酸、吲哚洛芬、吡洛芬、卡洛芬、噁丙秦、普拉洛芬、咪洛芬、硫噁洛芬、舒洛芬、阿明洛芬和噻洛芬酸。5) Propionic acid derivatives such as ibuprofen, methoxymethyl naphthaleneacetic acid, benzoxaprofen, flurbiprofen, ketopropionic acid, phenoxyprofen, biphenbutyric acid, indole Profen, pirprofen, carprofen, oxaprofen, pranoprofen, miprofen, thioxaprofen, suprofen, alminoprofen, and tiaprofen.
6)吡唑类如苯基丁氮酮、羟布宗、非普拉宗、阿拉丙宗和三甲保秦松。6) Pyrazoles such as phenylbutazone, hydroxybutazone, fiprazone, alapropanzone, and trimetazol.
还可以使用这些非甾族抗炎剂的混合物及其化妆品和/或药物可接受的盐和这些试剂的酯。例如依托芬那酯(氟灭酸的衍生物)特别适用于局部涂敷。在这些非甾族抗炎剂中,异丁苯丙酸、甲氧基甲基萘乙酸、氟灭酸、etofenamate、阿司匹林、甲灭酸、甲氯灭酸、吡罗昔康和联苯乙酸是优选的;异丁苯丙酸、甲氧基甲基萘乙酸、etofenamate、阿司匹林和氟灭酸是最优选的。Mixtures of these non-steroidal anti-inflammatory agents and their cosmetically and/or pharmaceutically acceptable salts and esters of these agents may also be used. For example etofenamate (a derivative of flufenamic acid) is particularly suitable for topical application. Among these non-steroidal anti-inflammatory agents, ibuprofen, methoxymethyl naphthaleneacetic acid, flufenamic acid, etofenamate, aspirin, mefenamic acid, meclofenamic acid, piroxicam and felbinac are preferred ; ibuprofen, methoxymethyl naphthaleneacetic acid, etofenamate, aspirin and flufenamic acid are most preferred.
最后,本发明的方法中可使用所谓“天然”抗炎症试剂。这些试剂可以从天然源(如植物、真菌、微生物副产物)采用适当物理和/或化学分离法以提取物形式获得。例如,可以使用小烛树蜡、α-红没药醇、芦荟、Manjistha(从Rubia属,特别是Rubia Cordifolia植物中提取)、Guggal(从Commiphora属,特别是Commiphora Mulkul植物中提取)、可拉提取物、春黄菊、和sea whip提取物。Finally, so-called "natural" anti-inflammatory agents may be used in the methods of the invention. These agents may be obtained in the form of extracts from natural sources (eg plants, fungi, microbial by-products) by appropriate physical and/or chemical isolation. For example, candelilla wax, alpha-bisabolol, aloe vera, Manjistha (extracted from plants of the genus Rubia, especially Rubia Cordifolia), Guggal (extracted from plants of the genus Commiphora, especially Commiphora Mulkul), kola extract, chamomile, and sea whip extract.
这里采用的其它抗炎剂包括甘草(植物属/种Glycyrrhiza glabra)科的化合物,包括甘草亭酸、甘草酸及其衍生物(如盐和酯)。上述化合物适合的盐包括金属盐和铵盐。适合的酯包括该酸的C2-C24饱和或不饱和酯,优选C10-C24酯,更优选C16-C24酯。上述物质具体的实例包括油溶性甘草提取物、甘草酸和甘草亭酸本身、甘草酸单铵盐、甘草酸单钾盐、甘草酸二钾盐、1-β-甘油亭酸、甘草亭酸硬脂酯、3-硬脂氧基-甘油亭酸和3-琥珀氧基-β-甘油亭酸二钠盐。优选甘草亭酸硬脂酯。局部麻醉剂Other anti-inflammatory agents useful herein include compounds of the Glycyrrhizae (genus/species Glycyrrhiza glabra) family, including glycyrrhetinic acid, glycyrrhizic acid and derivatives (eg, salts and esters) thereof. Suitable salts of the above compounds include metal salts and ammonium salts. Suitable esters include C2-C24 saturated or unsaturated esters of the acid, preferably C10-C24 esters, more preferably C16-C24 esters. Specific examples of the aforementioned substances include oil-soluble licorice extract, glycyrrhizic acid and glycyrrhetinic acid itself, glycyrrhizic acid monoammonium salt, glycyrrhizic acid monopotassium salt, glycyrrhizic acid dipotassium salt, 1-β-glycetinic acid, glycyrrhetinic acid Fatty esters, 3-stearyloxy-glycerate and 3-succinyloxy-β-glycerate disodium salt. Stearyl glycyrrhetinate is preferred. local anesthetic
本发明组合物还可包含安全有效量的局部麻醉剂。局麻药物的实例包括苯唑卡因、利多卡因、布比卡因、氯普鲁卡因、待布卡因、依铁卡因、甲哌卡因、丁卡因、达克罗宁、己卡因、普鲁卡因、可卡因、氯胺酮、丙吗卡因、苯酚、及其药物上可接受的盐。晒黑活性物The compositions of the present invention may also contain a safe and effective amount of a local anesthetic. Examples of local anesthetics include benzocaine, lidocaine, bupivacaine, chloroprocaine, tobucaine, eticaine, mepivacaine, tetracaine, dyclonine, Hexycaine, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically acceptable salts thereof. tanning actives
本发明组合物可含有晒黑活性物。当存在时,优选组合物含有占其重量约0.1%至约20%、更优选约2%至约7%,再优选约3%至约6%的二羟基丙酮人工晒黑活性物。The compositions of the present invention may contain tanning actives. When present, preferred compositions contain from about 0.1% to about 20%, more preferably from about 2% to about 7%, still more preferably from about 3% to about 6%, by weight of dihydroxyacetone artificial tanning active.
二羟基丙酮也称为DHA或1,3-二羟基-2-丙酮,它是白色至灰白的结晶粉末。该物质可由化学式C3H6O3和以下化学结构式表示:该化合物可以单体和二聚体的混合物形式存在,其中二聚体主要为固态结晶状。加热或熔化时,二聚体破裂产生单体。这种二聚体向单体的转化也出现在水溶液中。二羟基丙酮在酸性pH值下更稳定是公所周知的。参见《默克索引》,第10版,第3167条,第463页(1983),和《化妆品用二羟基丙酮》,E.Merck Technical Bulletin,03-304110,319897,180588。皮肤增白剂Dihydroxyacetone, also known as DHA or 1,3-dihydroxy-2-propanone, is a white to off-white crystalline powder. The substance can be represented by the chemical formula C 3 H 6 O 3 and the following chemical structural formula: The compound can exist as a mixture of monomers and dimers, where the dimers are mainly solid crystalline. When heated or melted, the dimer breaks down to produce monomers. This conversion of dimers to monomers also occurs in aqueous solutions. Dihydroxyacetone is known to be more stable at acidic pH. See The Merck Index, 10th Edition, Item 3167, p. 463 (1983), and Dihydroxyacetone for Cosmetics, E. Merck Technical Bulletin, 03-304110, 319897, 180588. skin brightener
本发明的组合物内可含有皮肤增白剂。当使用时,组合物优选的是含有其重量的约0.1%到约10%,更优选的是约0.2%到约5%,同样优选的是约0.5%约2%的皮肤增白剂。合适的皮肤增白剂包括那些在本技术领域内已知的物质,包括曲酸、熊果苷、抗坏血酸及其衍生物,如抗坏血酸磷酸镁或抗坏血酸磷酸钠。在此适用的皮肤增白剂也包括那些在以Hillebrand的名义于1995年6月7日申请的共同待审专利申请No.08/479,935(对应于PCT申请US 95/07432,申请日6/12/95)和以KallaL.Kvalnes,Mitchell A.DeLong,Barton J.Bradbury,Curtis B.Motley和John D.Carter的名义于1995年2月24日申请的共同待审申请序列号08/390,152(对应于PCT申请95/02809,申请日3/1/95,公开日9/8/95)中描述的物质。抗微生物和抗真菌活性物Skin lightening agents may be included in the compositions of the present invention. When used, the compositions preferably contain from about 0.1% to about 10%, more preferably from about 0.2% to about 5%, and also preferably from about 0.5% to about 2%, by weight of a skin lightening agent. Suitable skin lightening agents include those known in the art, including kojic acid, arbutin, ascorbic acid and derivatives thereof, such as magnesium ascorbyl phosphate or sodium ascorbyl phosphate. Skin lightening agents suitable herein also include those described in co-pending patent application No. 08/479,935 filed June 7, 1995 in the name of Hillebrand (corresponding to PCT application US 95/07432, filed 6/12 /95) and co-pending application Serial No. 08/390,152 filed February 24, 1995 in the names of Kalla L. Kvalnes, Mitchell A. DeLong, Barton J. Bradbury, Curtis B. Motley and John D. Carter (corresponding Substances described in PCT application 95/02809, filed 3/1/95, published 9/8/95). Antimicrobial and antifungal actives
本发明组合物可含有抗微生物或抗真菌活性物。这类活性物能破坏微生物,防止其生长或致病行为。可将安全有效量的抗微生物或抗真菌活性物加入本发明组合物,优选加入约0.001%至约10%,更优选约0.01%至约5%,最优选约0.05%至约2%。Compositions of the present invention may contain antimicrobial or antifungal actives. Such actives destroy microorganisms, preventing their growth or pathogenic behaviour. A safe and effective amount of an antimicrobial or antifungal active may be incorporated into the compositions of the present invention, preferably from about 0.001% to about 10%, more preferably from about 0.01% to about 5%, most preferably from about 0.05% to about 2%.
抗微生物和抗真菌活性物的例子有:β-内酰胺类药、喹诺酮类药物、环丙氟氯霉素、诺氟沙星、四环素、红霉素、阿米卡星、2,4,4’-三氯-2’-羟基二苯醚、3,4,4’-三氨对称二苯脲、苯氧基乙醇、苯氧基丙醇、苯氧基异丙醇、强力霉素、缠霉素、洗必汰、金霉素、土霉素、氯林肯霉素、乙氨丁醇、羟乙磺酸己脒定、甲哨唑、戊脒定、庆大霉素、卡那霉素、线霉素,甲烯土霉素、乌洛品托、二甲胺四环素、新霉素、奈替米星、巴龙霉素、链霉素、托普霉素、双氯苯咪唑、四环素盐酸化物、红霉素、锌红霉素、无味红霉素、红霉素硬脂酸盐、硫酸阿米卡星、多西环素盐酸盐、硫酸线霉素、葡萄糖酸洗必汰、盐酸洗必汰、盐酸金霉素、盐酸土霉素、盐酸氯林肯霉素、盐酸乙氨丁醇、盐酸甲哨唑、盐酸戊脒定、硫酸庆大霉素、硫酸卡那霉素、盐酸线霉素、盐酸甲烯土霉素、马尿酸乌洛托品、扁桃酸乌洛托品、盐酸二甲胺四环素、硫酸新霉素、硫酸奈替米星、硫酸巴龙霉素、硫酸链霉素、硫酸托普霉素、盐酸双氯苯咪唑、盐酸amanfadine、硫酸amanfadine、羟甲辛吡酮、对氯间二甲苯酚、制霉菌素、癣退、2-巯基吡啶氧化锌和克霉唑。Examples of antimicrobial and antifungal actives are: beta-lactams, quinolones, ciprofloxacin, norfloxacin, tetracyclines, erythromycin, amikacin, 2,4,4 '-Trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trihydrosymmetric diphenylurea, phenoxyethanol, phenoxypropanol, phenoxyisopropanol, doxycycline, Amycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, hexamidine isethionate, metronidazole, pentamidine, gentamicin, kanamycin , clindamycin, methacycline, uropintor, minocycline, neomycin, netilmicin, paromomycin, streptomycin, tobramycin, diclobendazole, tetracycline Hydrochloride, Erythromycin, Zinc Erythromycin, Odorless Erythromycin, Erythromycin Stearate, Amikacin Sulfate, Doxycycline Hydrochloride, Shrimycin Sulfate, Gluconic Acid Lahebutate, Chloridine hydrochloride, aureomycin hydrochloride, oxytetracycline hydrochloride, clindamycin hydrochloride, ethambutol hydrochloride, metronidazole hydrochloride, pentamidine hydrochloride, gentamicin sulfate, kanamycin sulfate, hydrochloric acid Linomycin, oxytetracycline hydrochloride, urotropine hippurate, urotropine mandelate, minocycline hydrochloride, neomycin sulfate, netilmicin sulfate, paromomycin sulfate, chain sulfate Amycin, tobramycin sulfate, diclobendazole hydrochloride, amanfadine hydrochloride, amanfadine sulfate, octopyrone, p-chloro-m-xylenol, nystatin, ringworm, zinc pyrithione, and clotrimycin azole.
这里有用的优选的活性物的例子包括选自以下的物质:水杨酸、过氧化苯甲酰、3-羟基苯甲酸、乙醇酸、乳酸、4-羟基苯甲酸、乙酰基水杨酸、2-羟基丁酸、2-羟基戊酸、2-羟基己酸、顺-视黄酸、反-视黄酸、视黄醇、肌醇六磷酸、N-乙酰基-L-半胱氨酸、硫辛酸、壬二酸、花生四烯酸、过氧化苯甲酸、四环素、异丁苯丙酸、甲氧萘丙酸、氢化可的松、acetominophen、间苯二酚、苯氧基乙醇、苯氧基丙醇、苯氧基异丙醇、2,4,4’-三氯-2’-羟基二苯醚、3,4,4’-三氯对称二苯脲、羟甲辛吡酮、利多卡因盐酸盐、克霉唑、双氯苯咪唑、硫酸neocycin、和它们的混合物。防晒活性物Examples of preferred actives useful herein include those selected from the group consisting of salicylic acid, benzoyl peroxide, 3-hydroxybenzoic acid, glycolic acid, lactic acid, 4-hydroxybenzoic acid, acetylsalicylic acid, 2 -Hydroxybutyric acid, 2-hydroxyvaleric acid, 2-hydroxyhexanoic acid, cis-retinoic acid, trans-retinoic acid, retinol, phytic acid, N-acetyl-L-cysteine, Lipoic acid, azelaic acid, arachidonic acid, benzoic acid peroxide, tetracycline, ibuprofen, naproxen, hydrocortisone, acetominophen, resorcinol, phenoxyethanol, phenoxyethanol propanol, phenoxyisopropanol, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorodiphenylurea, octopyrone, lido Caine hydrochloride, clotrimazole, diclobendazole, neocycin sulfate, and mixtures thereof. sunscreen actives
皮肤暴露在紫外线下会造成过多鳞片和角质层组织的变化。因此,本发明的组合物任选的是含防晒活性物。这里的“防晒活性物”包括防晒剂和物理遮阳剂。合适的防晒活性物可以是有机或无机的。Skin exposure to UV rays can cause excessive scales and changes in the stratum corneum tissue. Accordingly, the compositions of the present invention optionally contain sunscreen actives. "Sunscreen active" as used herein includes sunscreens and physical sunscreens. Suitable sunscreen actives can be organic or inorganic.
大量常规防晒活性物适合这里使用。Segarin等人在化妆品科学技术(1972),第VIII章,第189页以后公开了许多合适的活性物。具体的合适防晒活性物例如包括对氨基苯甲酸、它的盐和衍生物(乙基、异丁基、甘油基酯,对二甲基氨基苯甲酸)、氨茴香酸酯(即邻氨基苯甲酸酯,甲基、薄荷基、苯基、苄基、苯基乙基、里哪基、萜品基和环己烯基酯);水杨酸酯(戊基、苯基、苄基、薄荷基、甘油基和一缩二丙二醇酯);肉桂酸衍生物(薄荷基和苄基酯、(α-苯基肉桂腈;丁基肉桂酰丙酮酸酯);二羟基肉桂酸衍生物(繖形酮、甲基繖形酮、甲基乙酰繖形酮);三羟基肉桂酸衍生物(七叶亭、甲基七叶亭、瑞香素、和葡糖苷、七叶苷和瑞香苷);烃类(二苯基丁二烯、1,2-二苯乙烯);二亚苄基丙酮和亚苄基乙酰苯;萘酚磺酸盐(2-萘酚-3,6-二磺酸和2-萘酚-6,8-二磺酸的钠盐);二羟基萘甲酸和它的盐;邻和对羟基联苯基二磺酸盐;香豆素衍生物(7-羟基、7-甲基、3-苯基);二唑(2-乙酰基-3-溴吲唑、苯基苯并噁唑、甲基萘噁唑、各种芳基苯并噻唑);奎宁盐(硫酸氢盐、硫酸盐、氯化物、油酸盐和单宁酸盐);喹啉衍生物(8-羟基喹啉盐、2-苯基喹啉);羟基或甲氧基取代的二苯酮;尿酸和vilouric酸;单宁酸和它的衍生物(例如六乙基醚);(丁基carbotol)(6-丙基胡椒基)醚;氢醌;二苯酮(羟苯、郜利苯酮、二氧苯酮、苯并间苯二酚、2,2’,4,4’-四羟基二苯酮、2,2’-二羟基-4,4’-二甲氧基二苯酮、奥它苯酮;4-异丙基-二苯甲酰基甲烷;丁基甲氧基苯甲酰基甲烷;氰基二苯基丙烯酸乙酯;奥克立林;3-(4’-甲基亚苄基萜烷-2-酮),和4-异丙基-二苯甲酰基甲烷。A wide variety of conventional sunscreen actives are suitable for use here. Segarin et al. in Cosmetic Science and Technology (1972), Chapter VIII, pp. 189ff, disclose a number of suitable actives. Specific suitable sunscreen actives include, for example, p-aminobenzoic acid, its salts and derivatives (ethyl, isobutyl, glyceryl esters, p-dimethylaminobenzoic acid), anthranilic acid esters (i.e. anthranil esters, methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl and cyclohexenyl esters); salicylates (pentyl, phenyl, benzyl, menthyl dipropylene glycol esters); cinnamic acid derivatives (menthyl and benzyl esters, (alpha-phenylcinnamonitrile; butylcinnamoyl acetonate); dihydroxycinnamic acid derivatives (umbrelliform ketone, methyl umbelliferone, methyl acetyl umbelliferone); trihydroxycinnamic acid derivatives (escin, methyl esculetin, daphnetin, and glucoside, escin and daphnetin); hydrocarbons (diphenylbutadiene, 1,2-stilbene); dibenzylideneacetone and benzylideneacetophenone; naphthol sulfonate (2-naphthol-3,6-disulfonic acid and 2- Naphthol-6,8-disulfonic acid sodium salt); dihydroxynaphthoic acid and its salts; o- and p-hydroxybiphenyl disulfonates; coumarin derivatives (7-hydroxy, 7-methyl , 3-phenyl); diazoles (2-acetyl-3-bromoindazole, phenylbenzoxazole, methylnaphthazole, various arylbenzothiazoles); quinine salts (bisulfate , sulfate, chloride, oleate and tannate); quinoline derivatives (8-hydroxyquinolinate, 2-phenylquinoline); hydroxyl or methoxy substituted benzophenones; uric acid and vilouric acid; tannic acid and its derivatives (e.g. hexaethyl ether); (butyl carbotol) (6-propyl piperonyl) ether; hydroquinone; Oxybenzone, benzoresorcinol, 2,2',4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, Otto Benzophenone; 4-Isopropyl-dibenzoylmethane; Butylmethoxybenzoylmethane; Ethyl cyanodiphenylacrylate; Octocrylene; 3-(4'-Methylbenzylideneterane -2-one), and 4-isopropyl-dibenzoylmethane.
其中,对甲氧基肉桂酸2-乙基己基酯(商品有PARSOL MCX)、4,4’-叔丁基甲氧基二苯甲酰基甲烷(商品有PARSOL 1789)、2-羟基-4-甲氧基二苯酮、辛基二甲基-对氨基苯甲酸、二棓酰三油酸酯、2,2-二羟基-4-甲氧基二苯酮、4-(双(羟丙基))氨基苯甲酸乙基酯、2-氰基-3,3-二苯基丙烯酸2-乙基己基酯、水杨酸2-乙基己基酯、对氨基苯甲酸甘油酯、水杨酸3,3,5-三甲基环己基酯、氨茴香酸甲基酯、对二甲基氨基苯甲酸或氨基苯甲酸酯、对二甲基氨基苯甲酸2-乙基己基酯、2-苯基苯并咪唑-5-磺酸、2-(对二甲基氨苯基)-5-磺基苯并噁唑酸(benzoxazoic acid)、奥克立林和这些化合物的混合物是优选的。Among them, 2-ethylhexyl p-methoxycinnamate (commercially available as PARSOL MCX), 4,4'-tert-butylmethoxydibenzoylmethane (commercially available as PARSOL 1789), 2-hydroxy-4-methoxy benzophenone, octyldimethyl-p-aminobenzoic acid, digalloyl trioleate, 2,2-dihydroxy-4-methoxybenzophenone, 4-(bis(hydroxypropyl)) Ethyl aminobenzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, 2-ethylhexyl salicylate, glyceryl p-aminobenzoate, 3,3 salicylic acid , 5-trimethylcyclohexyl ester, methyl anthranisate, p-dimethylaminobenzoic acid or aminobenzoate, 2-ethylhexyl p-dimethylaminobenzoate, 2-phenylbenzene Imidazole-5-sulfonic acid, 2-(p-dimethylaminophenyl)-5-sulfobenzoxazoic acid, octocrylene and mixtures of these compounds are preferred.
可用于本发明的组合物中的更优选的有机防晒剂是2-乙基己基-对甲氧基肉桂酸酯、丁基甲氧基二苯甲酰基甲烷、2-羟基-4-甲氧基二苯酮、2-苯基苯并咪唑-5-磺酸、辛基二甲基-对氨基苯甲酸、奥克立林及其混合物。More preferred organic sunscreens for use in the compositions of the present invention are 2-ethylhexyl-p-methoxycinnamate, butylmethoxydibenzoylmethane, 2-hydroxy-4-methoxydiphenyl Ketones, 2-phenylbenzimidazole-5-sulfonic acid, octyldimethyl-p-aminobenzoic acid, octocrylene and mixtures thereof.
同样特别适合用于本发明组合物中的是(例如)1990年6月26日授予Sabatelli的US 4,937,370和1991年3月12日授予Sabatelli和Spirnak的US 4,999,186中公开的那些防晒剂。其中公开的防晒剂在一个分子中具有两个显示不同紫外辐射吸收谱的不同生色团部分。其中一个生色团部分主要在UVB辐射范围内吸收,而另一个生色团部分主要在UNA辐射范围内吸收。Also particularly suitable for use in the compositions of the present invention are sunscreens such as those disclosed in US 4,937,370, issued June 26, 1990 to Sabatelli and US 4,999,186, issued March 12, 1991 to Sabatelli and Spirnak. The sunscreens disclosed therein have two different chromophore moieties in one molecule which exhibit different absorption spectra of ultraviolet radiation. One of the chromophore moieties absorbs primarily in the UVB radiation range, while the other chromophore moiety absorbs primarily in the UNA radiation range.
这类防晒剂中优选的是2,4-二羟基二苯酮的4-N,N-(2-乙基己基)甲基氨基苯甲酸酯、4-羟基二苯甲酰基甲烷的N,N-二-(2-乙基己基)-4-氨基苯甲酸酯、4-羟基二苯甲酰基甲烷的4-N,N-(2-乙基己基)甲基氨基苯甲酸酯、2-羟基-4-(2-羟基乙氧基)二苯酮的4-N,N-(2-乙基己基)甲基氨基苯甲酸酯、4-(2-羟乙基)二苯甲酰基甲烷的4-N,N-(2-乙基己基)甲基氨基苯甲酸酯、2-羟基-4-(2-羟基乙氧基)二苯酮的N,N-二-(2-乙基己基)-4-氨基苯甲酸酯、和4-(2-羟基乙氧基)二苯甲酰基甲烷的N,N-二-(2-乙基己基)-4-氨基苯甲酸酯及其混合物。Preferred in this class of sunscreens are 4-N,N-(2-ethylhexyl)methylaminobenzoate of 2,4-dihydroxybenzophenone, N of 4-hydroxydibenzoylmethane, N-di-(2-ethylhexyl)-4-aminobenzoate, 4-N,N-(2-ethylhexyl)methylaminobenzoate of 4-hydroxydibenzoylmethane, 4-N,N-(2-ethylhexyl)methylaminobenzoate of 2-hydroxy-4-(2-hydroxyethoxy)benzophenone, 4-(2-hydroxyethyl)diphenyl 4-N,N-(2-ethylhexyl)methylaminobenzoate of formylmethane, N,N-di-( 2-Ethylhexyl)-4-aminobenzoate, and N,N-bis-(2-ethylhexyl)-4-aminobenzene of 4-(2-hydroxyethoxy)dibenzoylmethane Formic esters and mixtures thereof.
尤其优选的防晒活性物包括4,4’-丁基甲氧基二苯甲酰基甲烷、2-乙基己基-p-甲氧基肉桂酸酯、苯基苯并咪唑磺酸和奥克立林。Particularly preferred sunscreen actives include 4,4'-butylmethoxydibenzoylmethane, 2-ethylhexyl-p-methoxycinnamate, phenylbenzimidazole sulfonic acid and octocrylene.
使用安全且有效用量的防晒活性物,典型的是组合物重量的约1%到约20%,更优选的是约2%到约10%。其准确用量取决于所选择的防晒活性物和所要求的防晒因子(SPF)。The sunscreen actives are used in safe and effective amounts, typically from about 1% to about 20%, more preferably from about 2% to about 10%, by weight of the composition. The exact amount used will depend on the sunscreen active selected and the desired Sun Protection Factor (SPF).
调理剂conditioner
本发明组合物可含有选自润湿剂、增湿剂或皮肤调理剂的调理剂。多种物质可用于此,每种的存在量为组合物重量的约0.01%至约20%,更优选约0.1%至约10%,最优选约0.5%至约7%。这些物质包含但不限于胍、乙醇酸和乙醇酸盐(如铵盐和季烷基铵盐);水杨酸;乳酸及乳酸盐(如铵盐和季烷基铵盐);多种形式的芦荟(如芦荟凝胶);多元醇如山梨醇、甘油、己三醇、丁三醇、丙二醇、丁二醇、己二醇等;聚乙二醇;糖(如蜜二糖)和淀粉;糖和淀粉衍生物(如烷氧基化葡萄糖、果糖);透明质酸;乳酰胺单乙醇胺;乙酰胺单乙醇胺;及其混合物。也适用于此的有US4976953(1990年12月11日)授权Orr等人的丙氧基化甘油。Compositions of the present invention may contain conditioning agents selected from humectants, moisturizers or skin conditioning agents. A variety of materials are useful herein, each present at from about 0.01% to about 20%, more preferably from about 0.1% to about 10%, most preferably from about 0.5% to about 7%, by weight of the composition. These substances include, but are not limited to, guanidine, glycolic acid and glycolate salts (such as ammonium and quaternary ammonium salts); salicylic acid; lactic acid and lactate salts (such as ammonium and quaternary alkyl ammonium salts); various forms Aloe vera (such as aloe vera gel); polyols such as sorbitol, glycerin, hexanetriol, butylene glycol, propylene glycol, butylene glycol, hexylene glycol, etc.; polyethylene glycol; sugars (such as melibiose) and starch ; sugar and starch derivatives (eg, alkoxylated glucose, fructose); hyaluronic acid; lactamide monoethanolamine; acetamide monoethanolamine; and mixtures thereof. Also suitable for use herein are the propoxylated glycerols of US4976953 (December 11, 1990) to Orr et al.
也适用此的是糖及其相关物质的各种C1-C30单酯或多酯。这些酯衍生自糖或多元醇部分与一种或多种羧酸部分。这些酯还描述于以下文献中:1977年1月25日授权Jandacek的US 2831854和US 4005195;1994年4月26日授权Letton等人的US 5306516;1994年4月26日授权Letton等人的US 5306515;1994年4月26日授权Letton等的US 5305514;1989年1月10日授权Jandacek等的US 4797300;1976年6月15日授权Rizzi等的US 3963699;1985年5月21日授权Volpenhein的US 4518772;和1985年5月21日授权Volpenhein的US 4517360。增稠试剂(包括增稠剂和胶凝剂)Also suitable herein are the various C 1 -C 30 mono- or polyesters of sugars and related materials. These esters are derived from a sugar or polyol moiety and one or more carboxylic acid moieties. These esters are also described in US 2,831,854 and US 4,005,195, Jandacek, Jan. 25, 1977; US 5,306,516, Apr. 26, 1994, Letton et al.; 5306515; US 5305514 issued April 26, 1994 to Letton et al; US 4797300 issued January 10, 1989 to Jandacek et al; US 3963699 issued June 15, 1976 to Rizzi et al; issued May 21, 1985 to Volpenhein US 4,518,772; and US 4,517,360, issued May 21, 1985 to Volpenhein. Thickening agents (including thickeners and gelling agents)
本发明组合物可以包含一种或多种增稠试剂,优选组合物重量的约0.1%至约5%,更优选约0.1%至约3%,和最优选约0.25%至约2%的增稠试剂。The compositions of the present invention may comprise one or more thickening agents, preferably from about 0.1% to about 5%, more preferably from about 0.1% to about 3%, and most preferably from about 0.25% to about 2%, by weight of the composition. Thick reagent.
增稠试剂的非限制性实例包括选自以下的物质:a)羧酸聚合物Non-limiting examples of thickening agents include materials selected from the group consisting of: a) carboxylic acid polymers
这些聚合物是含一种或多种来自丙烯酸、取代丙烯酸及这些丙烯酸和取代丙烯酸的盐和酯衍生的单体的交联化合物,其中交联剂含两个或两个以上碳-碳双键并衍生自多元醇。1992年2月11日授权Haffey等人的U.S.P No.5,087,445;1985年4月5日授权Huang等人的U.S.P No.4,509,949;1957年7月2日授权Brown的U.S.P No.2,798,053中对本发明中使用的聚合物有更详实的描述。再参考《CTFA 国际化妆品成分词典》,第4版,1991,pp.12和80。These polymers are crosslinked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acid, and salts and esters of these acrylic acid and substituted acrylic acid, wherein the crosslinking agent contains two or more carbon-carbon double bonds and derived from polyols. U.S.P No. 5,087,445 issued February 11, 1992 to Haffey et al; U.S.P No. 4,509,949 issued April 5, 1985 to Huang et al; U.S.P No. 2,798,053 issued July 2, 1957 to Brown for use in the present invention polymers are described in more detail. Refer again to "CTFA International Cosmetic Ingredient Dictionary", 4th Edition, 1991, pp.12 and 80.
本发明所用的市售羧酸聚合物的例子包括聚羧乙烯制剂(carbomer),它是用蔗糖或季戊四醇的烯丙基醚交联的丙烯酸均聚物。商品化的聚羧乙烯制剂为古德里奇公司生产的Carbopol 900系列(如Carbopol954)。另外,其它适用的羧酸聚合物试剂包括丙烯酸C10~C30烷基酯与一种或多种单体的共聚物,这些单体可以是丙烯酸,甲基丙烯酸或它们的短链(即C1~C4醇)酯中的一种,其中交联剂是蔗糖或季戊四醇的烯丙基醚。已知这些共聚物为丙烯酸酯/丙烯酸C10~C30烷基酯的交联聚合物,市售的这些聚合物有古德里奇公司生产的Carbopol1342,Carbopol1382,Pemulen TR-1和Pemulen TR-2。换句话说,本发明所用的羧酸聚合物增稠剂选自聚羧乙烯制剂,丙烯酸酯/丙烯酸C10~C30烷基酯的交联聚合物,以及它们的混合物。b)交联聚丙烯酸酯聚合物Examples of commercially available carboxylic acid polymers useful in the present invention include carbomers, which are homopolymers of acrylic acid crosslinked with sucrose or allyl ethers of pentaerythritol. Commercially available carbopol preparations are Carbopol 900 series (such as Carbopol ® 954) produced by Goodrich Corporation. In addition, other suitable carboxylic acid polymer reagents include copolymers of C10-C30 alkyl acrylates and one or more monomers, which may be acrylic acid, methacrylic acid or short chains thereof (i.e. C1-C4 Alcohol) ester, wherein the crosslinking agent is allyl ether of sucrose or pentaerythritol. These copolymers are known as acrylate/acrylic acid C10~C30 alkyl ester cross-linked polymers, and these commercially available polymers have Carbopol ® 1342 produced by Goodrich, Carbopol ® 1382, Pemulen TR-1 and Pemulen TR -2. In other words, the carboxylic acid polymer thickener used in the present invention is selected from carbopol preparations, cross-linked polymers of acrylate/C10-C30 alkyl acrylate, and mixtures thereof. b) Cross-linked polyacrylate polymer
本发明组合物任选包含的用作增稠剂或凝胶剂的交联聚丙烯酸酯聚合物包括阳离子型和非离子型聚合物,通常优选的是阳离子型聚合物。在1992年3月31日授权Hawe等人的U.S.P 5,100,660;1989年7月18日授权Heard的U.S.P 4,849,484;1989年5月30日授权Farrar等人的U.S.P 4,835,206;1986年12月9日授权Glover等人的U.S.P4,628,078;1986年7月8日授权Flesher等人的U.S.Patent 4,599,379;1987年7月15日公开的Farrar等人EP 228,868中描述了一些本发明中使用的交联的非离子型聚丙烯酸酯聚合物和交联的阳离子型聚丙烯酸酯聚合物的例子。c)聚丙烯酰胺聚合物The crosslinked polyacrylate polymers optionally included in the compositions of the present invention for use as thickeners or gelling agents include cationic and nonionic polymers, with cationic polymers generally being preferred. U.S.P 5,100,660 issued March 31, 1992 to Hawe et al; U.S.P 4,849,484 issued July 18, 1989 to Heard; U.S.P 4,835,206 issued May 30, 1989 to Farrar et al; issued December 9, 1986 to Glover et al U.S.P. 4,628,078 to Man; U.S. Patent 4,599,379 to Flesher et al., issued July 8, 1986; and Farrar et al. EP 228,868, published July 15, 1987. Examples of polyacrylate polymers and crosslinked cationic polyacrylate polymers. c) Polyacrylamide polymer
本发明组合物可任选地含有聚丙烯酰胺聚合物,特别是包含被取代的支化的或无支链的聚合物的非离子型聚丙烯酰胺聚合物。这些聚丙烯酰胺聚合物中再优选的是具有CTFA名称聚丙烯酰胺和异链烷烃和月桂基醚-7的非离子型聚合物,是Seppic Corporation(Fairfield,NJ)出产的商品名为Sepigel 305的产品。The compositions of the present invention may optionally contain polyacrylamide polymers, especially nonionic polyacrylamide polymers comprising substituted branched or unbranched polymers. Still more preferred among these polyacrylamide polymers is the nonionic polymer having the CTFA designation polyacrylamide and isoparaffin and lauryl ether-7, available under the tradename Sepigel 305 from Seppic Corporation (Fairfield, NJ). product.
本发明中所用的其他聚丙烯酰胺聚合物包括丙烯酰胺和由丙烯酸和取代的丙烯酸取代的丙烯酰胺的多嵌段共聚物。这种多嵌段共聚物的市售的例子包括Lipo Chemicals,Inc.,(Patterson,NJ)出产的HypanSRl50H,SS500V,SS500W,SSSA1OOH。d)多糖Other polyacrylamide polymers useful in the present invention include multi-block copolymers of acrylamide and acrylamide substituted with acrylic acid and substituted acrylic acid. Commercially available examples of such multi-block copolymers include Hypan SR150H, SS500V, SS500W, SSSA100H from Lipo Chemicals, Inc., (Patterson, NJ). d) polysaccharide
本发明中使用多种多糖。“多糖”意为含重复糖(即碳水化合物)单元骨架的凝胶剂。多糖凝胶剂的非限制性的例子选自纤维素,羧甲基羟乙基纤维素,醋酸丙酸羧酸纤维素,羟乙基纤维素,羟乙基乙基纤维素,羟丙基纤维素,羟丙基甲基纤维素,甲基羟乙基纤维素,微晶纤维素,硫酸纤维素钠,以及它们的混合物。本发明中还可使用烷基取代纤维素。在这些聚合物中,纤维素聚合物中的羟基基团羟烷基化(优选的是羟乙基化或羟丙基化)形成羟烷基化纤维素,该羟烷基化纤维素然后由C10-C30直链或支链烷基基团通过醚键进一步改性。这些聚合物典型的是羟烷基纤维素与C10-C30直链或支链醇的醚。这里所用的烷基基团可以选自硬脂基,异硬脂基,月桂基,肉豆蔻基,鲸蜡基,异鲸蜡基,椰油基(即由椰子油的醇衍生的烷基基团),棕榈基,油基,亚油基,亚麻基,蓖麻基,二十二烷基,以及它们的混合物。烷基羟烷基纤维素醚中优选的是那些具有CTFA名称鲸蜡基羟乙基纤维素的原料,它是一种鲸蜡醇和羟乙基纤维素的醚。Aqualon Corporation(Wilmington,DE)以商品名NatrosolCSPlus出售这些原料。A variety of polysaccharides are used in the present invention. "Polysaccharide" means a gelling agent having a backbone of repeating sugar (ie, carbohydrate) units. Non-limiting examples of polysaccharide gelling agents are selected from cellulose, carboxymethyl hydroxyethyl cellulose, cellulose acetate propionate carboxylate, hydroxyethyl cellulose, hydroxyethyl ethyl cellulose, hydroxypropyl cellulose Hydroxypropylmethylcellulose, methylhydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Alkyl-substituted celluloses can also be used in the present invention. In these polymers, the hydroxyl groups in the cellulosic polymer are hydroxyalkylated, preferably hydroxyethylated or hydroxypropylated, to form hydroxyalkylated cellulose, which is then formed from C10-C30 linear or branched alkyl groups are further modified by ether linkages. These polymers are typically ethers of hydroxyalkylcelluloses with C10-C30 linear or branched chain alcohols. The alkyl group used herein may be selected from the group consisting of stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, cocoyl (i.e. the alkyl group derived from the alcohol of coconut oil group), palmityl, oleyl, linoleyl, linolyl, castoryl, behenyl, and mixtures thereof. Preferred among the alkyl hydroxyalkyl cellulose ethers are those having the CTFA designation cetyl hydroxyethyl cellulose, which is an ether of cetyl alcohol and hydroxyethyl cellulose. Aqualon Corporation (Wilmington, DE) sells these materials under the tradename Natrosol® CSPlus.
其他所用的多糖包括含(1-3)连接的葡萄糖单元、而每三个糖单元就具有一个(1-6)连结的葡萄糖的线型链的硬葡聚糖,其市售的实例是Michel Mercier Products Inc.(Mountainside,NJ)出产的Clearogel TMCSll。e)胶Other polysaccharides used include scleroglucans containing (1-3) linked glucose units with linear chains of (1-6) linked glucose units for every three sugar units, a commercial example of which is Michel Clearogel TMCS 11 from Mercier Products Inc. (Mountainside, NJ). e) Glue
本发明中使用的其他增稠剂凝胶剂包括主要由天然源衍生的物质。这些凝胶剂胶的非限制性的例子包括选自以下的物质:阿拉伯胶,琼脂,藻酸,藻酸铵,支链淀粉,藻酸钙,角叉菜胶钙,肉碱,角叉菜胶,糊精,明胶,gellan胶,瓜耳豆胶,瓜耳胶羟丙基三甲基铵的氯化物(guarhydroxypropyltrimonium chloride),水辉石润滑脂,透明质酸,水化硅石,羟丙基脱乙酸壳多糖,羟丙基瓜耳胶,刺梧桐树胶,海草,刺槐豆胶,纳豆胶,藻酸钾,角叉菜胶钾,藻酸丙二醇酯,菌核胶,羧甲基葡聚糖钠,角叉菜胶钠,黄蓍胶,黄原胶,及其混合物。Other thickener gelling agents useful in the present invention include materials derived primarily from natural sources. Non-limiting examples of these gelling agent gums include substances selected from the group consisting of: gum arabic, agar, alginic acid, ammonium alginate, pullulan, calcium alginate, calcium carrageenan, carnitine, carrageenan Gum, dextrin, gelatin, gellan gum, guar gum, guarhydroxypropyltrimonium chloride, hectorite grease, hyaluronic acid, hydrated silica, hydroxypropyl Chitosan, Hydroxypropyl Guar Gum, Karaya Gum, Seaweed, Locust Bean Gum, Natto Gum, Potassium Alginate, Potassium Carrageenan, Propylene Glycol Alginate, Sclerotin Gum, Carboxymethyl Dextrose Sodium sugar, sodium carrageenan, gum tragacanth, xanthan gum, and mixtures thereof.
本发明优选的组合物包括选自以下的增稠试剂:羧酸聚合物、交联的聚丙烯酸酯聚合物、聚丙烯酰胺聚合物及其混合物,更优选羧酸聚合物、聚丙烯酰胺聚合物及其混合物。Preferred compositions of the present invention include a thickening agent selected from the group consisting of carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers and mixtures thereof, more preferably carboxylic acid polymers, polyacrylamide polymers and mixtures thereof.
虽然许多任选组分可包括在本发明的组合物中,该组合物优选没有类视色素,尤其是当这类组合物欲用于调节哺乳动物皮肤质地可见的和/或可触觉的不连续性时。另外,当这类组合物用于防止和减缓瘙痒时优选没有普鲁卡因。这里使用的“没有”指在组合物中检测不到该化合物或组分。组合物制备方法Although a number of optional components may be included in the compositions of the present invention, the compositions are preferably free of retinoids, especially when such compositions are intended to adjust visible and/or tactile discontinuities in the texture of mammalian skin hour. Additionally, procaine is preferably absent when such compositions are used to prevent and relieve itching. "Absent" as used herein means that the compound or component is not detectable in the composition. Composition preparation method
本发明组合物的制备方法一般是制备局部用组合物领域中已知的传统方法。这些方法一般涉及在一步或多步中将各成分混成相对均匀的状态,可以或不用加热、冷却、加真空等。调节皮肤状况的方法Methods of preparation of the compositions of the present invention are generally conventional methods known in the art of preparing topical compositions. These methods generally involve mixing the ingredients into a relatively uniform state in one or more steps, with or without heating, cooling, vacuum, and the like. Ways to Regulate Skin Condition
本发明组合物用于调节哺乳动物角质组织状况,即皮肤状况。这种调节包括预防性和治疗性调节。更具体地说,这种调节方法指防止和/或阻碍哺乳动物皮肤毛细血管和/或红斑的外观,防止和/或阻碍哺乳动物眼下黑圈和/或松眼泡的外观,使哺乳动物皮肤脱屑,防止和/或阻碍哺乳动物肤色灰黄的外观,防止和/或阻碍哺乳动物皮肤下垂,软化和/或光滑哺乳动物的唇部、毛发和指甲,和防止和/或减轻哺乳动物皮肤的瘙痒。The compositions of the present invention are useful for regulating the condition of mammalian keratinous tissue, ie the condition of the skin. Such adjustments include preventive and therapeutic adjustments. More specifically, this modulating method refers to preventing and/or hindering the appearance of capillaries and/or erythema in mammalian skin, preventing and/or hindering the appearance of dark circles and/or puffy eye sockets in mammalian skin, desquamation of mammalian skin prevents and/or hinders the appearance of sallow skin in mammals, prevents and/or hinders sagging of mammalian skin, softens and/or smoothes lips, hair and nails of mammals, and prevents and/or lessens sagging of mammalian skin itching.
调节角质组织状况一般涉及向需要处理的哺乳动物的角质组织局部施用本发明的安全及有效量的组合物。组合物的施用量、施用频率和使用期间随给定组合物中所述黄嘌呤化合物和/或其它组分的含量以及所需调节的程度而有很大变化,例如参考皮肤损坏的程度和皮肤会进一步损坏的速率。Modulating the condition of keratinous tissue generally involves topically applying a safe and effective amount of a composition of the present invention to the keratinous tissue of a mammal in need of treatment. The amount of application, frequency of application and duration of use of the composition will vary greatly with the content of the xanthine compound and/or other components in a given composition and the degree of adjustment required, for example with reference to the degree of skin damage and skin damage. The rate at which further damage will occur.
在优选的实施方案中,将组合物长期地施用于皮肤。“长期局部施用”是指在个体生命的较长时间段内持续的施用组合物,优选至少约1周,更优选至少约1个月,再优选至少约3个月,再优选至少约6个月,再优选至少约1年。虽然在各种最长期间后(如五、十或二十年后)可以获得益处,但优选在个体的一生中长期施用。在这些期间,一般是每天约1次施用,但施用率可以从每周约一次至每天约3次或更多次。In a preferred embodiment, the composition is applied chronically to the skin. "Long-term topical administration" refers to the continuous application of the composition for an extended period of time in the individual's life, preferably at least about 1 week, more preferably at least about 1 month, more preferably at least about 3 months, and more preferably at least about 6 months. months, and preferably at least about 1 year. Chronic administration over the lifetime of the individual is preferred, although benefits may be obtained after various maximum periods of time, such as after five, ten or twenty years. During these periods, application is generally about once per day, but the rate of application can be from about once per week to about 3 or more times per day.
为给角质组织提供外观和/或感觉上的益处,可以在宽的用量范围内使用本发明组合物。组合物每次用量一般为(按毫克组合物/平方厘米皮肤计)约0.1mg/cm2至约10mg/cm2。尤其用量的施用量为约2mg/cm2。The compositions of the present invention may be used in a wide range of amounts to provide appearance and/or sensory benefits to keratinous tissue. The composition is generally used in an amount (in milligrams of composition per square centimeter of skin) of about 0.1 mg/cm 2 to about 10 mg/cm 2 . In particular the amount applied is about 2 mg/cm 2 .
优选地,实施调节皮肤状况具体是是通过水剂、乳膏、凝胶、泡沫、乳液、喷雾剂、调理剂、补剂、化妆品、唇膏、粉底、指甲油、剃须后护理剂或其它形式将组合物施用于皮肤或其它角蛋白结构上,以产生美感上的、预防性的、治疗性的或其它方面的益处(即“留存型”组合物)。向皮肤施用组合物后,优选将其留在皮肤上至少约15分钟,更优选至少约30分钟,更优选至少约1小时,最优选至少约几个小时,如达12小时。可以处理面部、毛发和/或指甲的外部的任何部位,如面、唇、眼下区域、眼睑、头皮、颈、躯干、臂、手、腿、指甲、趾甲、头皮毛发、睫毛、眉毛等。Preferably, regulating the condition of the skin is effected in particular by means of lotions, creams, gels, foams, lotions, sprays, conditioners, tonics, cosmetics, lipsticks, foundations, nail varnishes, after-shave treatments or other forms The compositions are applied to the skin or other keratinous structures to produce aesthetic, prophylactic, therapeutic or other benefits (ie "leave-on" compositions). After applying the composition to the skin, it is preferably left on the skin for at least about 15 minutes, more preferably at least about 30 minutes, more preferably at least about 1 hour, most preferably at least about several hours, such as up to 12 hours. Any part of the exterior of the face, hair and/or nails can be treated, such as face, lips, under-eye area, eyelids, scalp, neck, torso, arms, hands, legs, fingernails, toenails, scalp hair, eyelashes, eyebrows, etc.
另一种保证皮肤持续暴露于至少是最低量的所述黄嘌呤化合物的途径是通过使用贴片施用至例如面部来施加组合物。这种途径尤其适用于需要更深入的处理的有问题的皮肤区域(如面部眼角旁皱纹、眼下区域等)。该贴片可以是闭塞性的、半闭塞性的或非闭塞性的。含所述黄嘌呤化合物组合物可以包含于贴片中或在用贴片之前施加至皮肤上。贴片也可以包含其它活性物,如Burkett等人的PCT申请WO 9701313中描述的用于放热反应的化学引发剂。优选贴片留在皮肤上至少约5分钟,更优选至少约15分钟,再优选至少约30分钟,再优选至少约1小时,最优选约一夜的夜间治疗。Another way to ensure continued exposure of the skin to at least a minimum amount of said xanthine compounds is to apply the composition using a patch application to, for example, the face. This approach is especially useful for problematic areas of the skin that require more intensive treatment (such as facial creases, under-eye area, etc.). The patch can be occlusive, semi-occlusive or non-occlusive. The xanthine compound-containing composition may be included in a patch or applied to the skin prior to application of the patch. The patch may also contain other actives such as chemical initiators for exothermic reactions as described in PCT Application WO 9701313 by Burkett et al. Preferably the patch is left on the skin for at least about 5 minutes, more preferably at least about 15 minutes, still more preferably at least about 30 minutes, still more preferably at least about 1 hour, most preferably about overnight for an overnight treatment.
本发明组合物可以和使用说明一起提供给组合物的用户或潜在的用户(以下都称作“用户”),所述使用说明告诉用户通过使用该组合物将提供一种或多种有益效果,包括但不限于防止和/或阻碍哺乳动物皮肤毛细血管和/或红斑的外观,防止和/或阻碍哺乳动物眼下黑圈和松眼泡的外观,防止和/或阻碍哺乳动物肤色灰黄的外观,使哺乳动物皮肤脱屑,防止和/或阻碍哺乳动物皮肤下垂,软化和/或光滑哺乳动物的唇部、毛发和指甲,和防止和/或减轻哺乳动物皮肤的瘙痒等。该使用说明也可以包括用于获得这些有益效果的指导,例如包括以上所述方法步骤。“和使用说明一起提供”是指该使用说明或者是直接印刷在所述组合物的容器上(包括直接印在容器本身上或通过标签或附着物间接附在容器上),或者是以不同方式提供,包括但不限于小册子、印刷广告、电子广告和/或其它广告形式,以将该使用说明告知所述组合物的消费者。该使用说明可以相应地包括文字、图片等。Compositions of the present invention may be provided to users or potential users of the composition (hereinafter referred to as "users") together with instructions for use of the composition to provide one or more benefits, Including, but not limited to, preventing and/or hindering the appearance of capillaries and/or erythema in mammalian skin, preventing and/or hindering the appearance of dark circles and puffy eye pockets under the eyes of mammals, preventing and/or hindering the appearance of sallow complexion in mammals, Desquamation of mammalian skin, preventing and/or impeding sagging of mammalian skin, softening and/or smoothing of mammalian lips, hair and nails, and preventing and/or alleviating itching of mammalian skin, etc. The instructions for use may also include instructions for obtaining these benefits, for example including the method steps described above. "Accompanies instructions for use" means that the instructions for use are either printed directly on the container of the composition (including directly on the container itself or indirectly attached to the container by a label or sticker), or in a different manner Provide, including but not limited to, brochures, print advertisements, electronic advertisements, and/or other forms of advertisement, to inform consumers of the composition of the instructions for use. The instructions for use may include text, pictures and the like accordingly.
实施例Example
以下的实施例将进一步在本发明的范围内描述和说明具体的实施例。这些实施例仅仅是出于说明的目的,无意于对本发明有任何限制,在不违反本发明的主旨和范围的情况下,也可能会有很多种变化。The following examples will further describe and illustrate specific examples within the scope of the present invention. These embodiments are for the purpose of illustration only, and are not intended to limit the present invention, and many changes are possible without violating the spirit and scope of the present invention.
实施例1Example 1
从以下组分用传统方法制备护肤膏。
用适当的混合器(如Tekmar RW20DZM型号)混合A相组分,混合的同时加热以熔化组分。另外,用适当混合器混合除茶碱外的B相组分,搅拌的同时加热至70-75℃。在此温度下加入茶碱。另外,混合C相组分,搅拌的同时加热至70-75℃。在此温度下加入C相和B相并研磨5分钟(如用Tekmar T50磨机)。然后加入D相组分并混合5分钟。冷却至50℃,然后加入A相组分。Mix Phase A ingredients with a suitable mixer (such as Tekmar Model RW20DZM), heating while mixing to melt the ingredients. Separately, mix the Phase B ingredients except theophylline with a suitable mixer and heat to 70-75°C while stirring. Add theophylline at this temperature. Separately, mix Phase C ingredients and heat to 70-75°C while stirring. Add phases C and B at this temperature and grind for 5 minutes (eg with a Tekmar T50 mill). Then add Phase D ingredients and mix for 5 minutes. Cool to 50°C, then add Phase A ingredients.
将组合物加至需要处理的个体的面部皮肤上,用量为2mg组合物/cm2皮肤,一天一次或两次,持续至少3-6个月。The composition is applied to the facial skin of an individual in need of treatment in an amount of 2 mg composition/ cm2 of skin once or twice a day for at least 3-6 months.
实施例2Example 2
从以下组分用常规方法制备乳液。
在加有水的容器中如下形成A相(水相):在搅拌下逐渐将剩余组分加入并加热至55℃。Phase A (aqueous phase) was formed in a vessel with water by gradually adding the remaining components with stirring and heating to 55°C.
在另一容器中加入并搅拌B相组分形成B相组分。开始加热并搅拌至50℃。In a separate container add and stir the Phase B ingredients to form the Phase B ingredients. Start heating and stir to 50 °C.
在搅拌下将A相组分缓慢加至B相组分中,并研磨15分钟。Slowly add Phase A ingredients to Phase B ingredients with stirring and mill for 15 minutes.
将组合物加至需要处理的个体的面部皮肤上,用量为2mg组合物/cm2皮肤,一天一次或两次,持续至少3-6个月。The composition is applied to the facial skin of an individual in need of treatment in an amount of 2 mg composition/ cm2 of skin once or twice a day for at least 3-6 months.
实施例3Example 3
从以下组分用传统方法制备护肤膏。
用适当的混合器(如Tekmar RW20DZM型号)混合A相组分,混合的同时加热以熔化组分。另外,用适当混合器混合除可可碱外的B相组分,搅拌的同时加热至70-75℃。在此温度下加入可可碱。另外,混合C相组分,搅拌的同时加热至70-75℃。在此温度下加入C相和B相并研磨5分钟(如用Tekmar T50磨机)。然后加入D相组分并混合5分钟。冷却至50℃,然后加入A相组分。Mix Phase A ingredients with a suitable mixer (such as Tekmar Model RW20DZM), heating while mixing to melt the ingredients. Separately, mix the Phase B ingredients except theobromine with a suitable mixer and heat to 70-75°C while stirring. Add theobromine at this temperature. Separately, mix Phase C ingredients and heat to 70-75°C while stirring. Add phases C and B at this temperature and grind for 5 minutes (eg with a Tekmar T50 mill). Then add Phase D ingredients and mix for 5 minutes. Cool to 50°C, then add Phase A ingredients.
将组合物加至需要处理的个体的面部皮肤上,用量为2mg组合物/cm2皮肤,一天一次或两次,持续至少3-6个月。The composition is applied to the facial skin of an individual in need of treatment in an amount of 2 mg composition/ cm2 of skin once or twice a day for at least 3-6 months.
虽然已经描述了本发明的具体的实施例,但是本技术领域内的技术人员应知道,在不违反本发明的主旨和范围的情况下,本发明可以有很多改变和改进。在附加的权利要求书内,包括所有在本发明范围内的这类改进。Although specific embodiments of the present invention have been described, those skilled in the art will appreciate that many changes and modifications can be made to the present invention without departing from the spirit and scope of the present invention. It is intended to cover in the appended claims all such modifications which are within the scope of this invention.
Claims (10)
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US13466099P | 1999-05-18 | 1999-05-18 | |
US60/134,660 | 1999-05-18 |
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CN1355689A true CN1355689A (en) | 2002-06-26 |
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CN00808874A Pending CN1355689A (en) | 1999-05-18 | 2000-05-18 | Methods for regulating condition of mammalian keratinous tissue |
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EP (1) | EP1178776A1 (en) |
JP (1) | JP2002544218A (en) |
KR (1) | KR20020011988A (en) |
CN (1) | CN1355689A (en) |
AU (1) | AU5026800A (en) |
BR (1) | BR0010551A (en) |
CA (1) | CA2373194A1 (en) |
CZ (1) | CZ20014132A3 (en) |
MX (1) | MXPA01011866A (en) |
WO (1) | WO2000069408A1 (en) |
Cited By (1)
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CN108883098A (en) * | 2016-01-19 | 2018-11-23 | 雅珂马Z私人有限公司 | Cosmetic composition and application thereof for adjusting skin quality |
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US8039026B1 (en) | 1997-07-28 | 2011-10-18 | Johnson & Johnson Consumer Companies, Inc | Methods for treating skin pigmentation |
US8093293B2 (en) | 1998-07-06 | 2012-01-10 | Johnson & Johnson Consumer Companies, Inc. | Methods for treating skin conditions |
US8106094B2 (en) | 1998-07-06 | 2012-01-31 | Johnson & Johnson Consumer Companies, Inc. | Compositions and methods for treating skin conditions |
US6750229B2 (en) | 1998-07-06 | 2004-06-15 | Johnson & Johnson Consumer Companies, Inc. | Methods for treating skin pigmentation |
US8431550B2 (en) | 2000-10-27 | 2013-04-30 | Johnson & Johnson Consumer Companies, Inc. | Topical anti-cancer compositions and methods of use thereof |
US7192615B2 (en) | 2001-02-28 | 2007-03-20 | J&J Consumer Companies, Inc. | Compositions containing legume products |
US7851477B2 (en) | 2003-05-22 | 2010-12-14 | L'oreal | Method for the treatment of skin |
FR2855050B1 (en) * | 2003-05-22 | 2008-07-04 | Oreal | PROCESS FOR THE COSMETIC TREATMENT OF REDNESS |
KR100970006B1 (en) * | 2008-06-24 | 2010-07-15 | 주식회사 벤토피아 | Fixed vaporized humidifier |
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FR2556217A1 (en) * | 1983-12-09 | 1985-06-14 | Biosculpture | FATTY ANTI-OVERLOAD COSMETIC COMPOSITIONS AND IONOPHORESIS HUMAN BODY APPLICATION |
FR2668061A1 (en) * | 1990-10-19 | 1992-04-24 | Thorel Jean Noel | Cosmetic compositions for application around the eyes |
JPH0812519A (en) * | 1994-06-24 | 1996-01-16 | Kao Corp | Skin external preparation composition |
JP3447809B2 (en) * | 1994-07-12 | 2003-09-16 | 花王株式会社 | Bath agent |
FR2770776B1 (en) * | 1997-11-07 | 2000-03-17 | Lvmh Rech | USES OF D-XYLOSE AND ITS ESTERS TO IMPROVE THE FUNCTIONALITY OF SKIN CELLS |
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- 2000-05-18 EP EP00932566A patent/EP1178776A1/en not_active Withdrawn
- 2000-05-18 WO PCT/US2000/013647 patent/WO2000069408A1/en not_active Application Discontinuation
- 2000-05-18 CA CA002373194A patent/CA2373194A1/en not_active Abandoned
- 2000-05-18 CZ CZ20014132A patent/CZ20014132A3/en unknown
- 2000-05-18 MX MXPA01011866A patent/MXPA01011866A/en unknown
- 2000-05-18 JP JP2000617867A patent/JP2002544218A/en not_active Withdrawn
- 2000-05-18 CN CN00808874A patent/CN1355689A/en active Pending
- 2000-05-18 KR KR1020017014679A patent/KR20020011988A/en not_active Application Discontinuation
- 2000-05-18 BR BR0010551-1A patent/BR0010551A/en not_active IP Right Cessation
- 2000-05-18 AU AU50268/00A patent/AU5026800A/en not_active Abandoned
Cited By (3)
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CN108883098A (en) * | 2016-01-19 | 2018-11-23 | 雅珂马Z私人有限公司 | Cosmetic composition and application thereof for adjusting skin quality |
TWI743080B (en) * | 2016-01-19 | 2021-10-21 | 新加坡商雅珂馬Z私人有限公司 | A cosmetic composition and the use thereof for regulating skin quality |
CN108883098B (en) * | 2016-01-19 | 2023-12-19 | 雅珂马Z私人有限公司 | Cosmetic compositions for adjusting skin texture and uses thereof |
Also Published As
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JP2002544218A (en) | 2002-12-24 |
AU5026800A (en) | 2000-12-05 |
CA2373194A1 (en) | 2000-11-23 |
BR0010551A (en) | 2002-02-13 |
EP1178776A1 (en) | 2002-02-13 |
KR20020011988A (en) | 2002-02-09 |
MXPA01011866A (en) | 2002-05-06 |
WO2000069408A1 (en) | 2000-11-23 |
CZ20014132A3 (en) | 2002-05-15 |
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