CN118076335A - 外用滋养/抗菌组合物 - Google Patents
外用滋养/抗菌组合物 Download PDFInfo
- Publication number
- CN118076335A CN118076335A CN202280068167.4A CN202280068167A CN118076335A CN 118076335 A CN118076335 A CN 118076335A CN 202280068167 A CN202280068167 A CN 202280068167A CN 118076335 A CN118076335 A CN 118076335A
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- China
- Prior art keywords
- skin
- topical composition
- composition
- particles
- calcium phosphate
- Prior art date
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 49
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 48
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- 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
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/24—Phosphorous; Compounds thereof
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
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- A—HUMAN NECESSITIES
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- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
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Landscapes
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- Veterinary Medicine (AREA)
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- Epidemiology (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
提供了外用滋养/抗微生物组合物。组合物的实施方案包括微生物剂,例如季铵化合物,和磷酸钙颗粒,其中组合物可任选地包括一种或多种皮肤滋养剂。组合物的实施方案包括乳液和清洁剂。还提供了制备和使用所述组合物的方法。
Description
相关申请的交叉引用
根据35U.S.C.§119(e),本申请要求2021年9月21日提交的美国临时专利申请序列号63/246572的提交日的优先权;该申请的公开内容通过引用并入本文。
引言
皮肤是身体的外部覆盖物,可以防止热和光、伤害和感染。皮肤调节体温,储存水分、脂肪和维生素D。皮肤重约6磅,是人体最大的器官。它由两个主要层组成:表皮或表层,以及更深的结缔组织层,即真皮。当最外层的细胞脱落并被来自内部真皮层的细胞取代时,表皮会不断更新。真皮由多种细胞类型组成,包括成纤维细胞。
皮肤过度干燥是一个常见的问题,通常是暴露在风、阳光和低湿度下,或这些因素的组合造成的。频繁洗手也会导致过度干燥。如果使用研磨性肥皂、酒精类产品和其他刺激性化学品进行清洁,则情况更是如此。
过度干燥的皮肤不仅难看,而且容易严重蜕皮及开裂,导致皮肤表面擦伤。由于皮肤作为寄生虫和病原体进入的物理屏障发挥着关键作用,过度干燥会导致屏障被突破且被病原菌和真菌感染。因此,皮肤上的裂缝或开口充当病原体和潜在病原体的入口。即使是通常被认为是非病原体的生物体,也会导致免疫受损个体的机会性感染。感染可能是轻度或重度的,可能局限于感染的初始部位,也可能是全身性的并扩散遍及全身。这种扩散可能通过直接延伸到相邻组织,或者通过淋巴管,最终通过血液发生。
今天,人类面临的最大威胁之一是接触交叉污染的负面影响。大约80%的传染病是通过接触传播的,每年有数百万人死于传染病(美国疾病控制与预防中心(CDC)。美国疾病控制与预防中心感染控制公共信息快速参考指南(Centers for Disease Control andPrevention(CDC).CDC Quick Reference Guide for Public Information on InfectionControl)))。酒精类消毒液只有在酒精蒸发后才有效(数分钟)。此外,它们会使皮肤失去健康的天然油脂、水分和光泽,损害皮肤的天然屏障功能,导致皮炎,使皮肤干燥、开裂,易受细菌和病毒感染,对健康有毒害,对环境有害。
发明内容
提供了外用滋养/抗微生物组合物。组合物的实施方案包括抗微生物剂,例如季铵化合物和磷酸钙颗粒,其中组合物可任选地包括一种或多种皮肤滋养剂。组合物的实施方案包括有效但不含消毒剂/防腐醇如异丙醇和乙醇的乳液和清洁剂。还提供了制备和使用所述组合物的方法。
本发明的各方面提供了具有意想不到结果的外用制剂,其使用磷酸钙组分作为递送系统与制剂的钙和皮肤滋养剂(例如植物和草药提取物、抗炎药、抗氧化剂、维生素和润肤剂)结合并将钙和皮肤滋养剂的益处递送到皮肤中,其中它们从内而外起作用,同时消毒残留在皮肤表面的活性抗微生物剂(例如苯扎氯铵)并杀死99.9%的微生物(细菌、真菌和病毒),并提供数小时(1-24、2-15、3-10和4-8小时)的消毒保护,同时保湿和滋养皮肤。
定义
本文中通常使用的“掺混物”或“混合物”是指两种或更多种不同组分的物理组合。
所谓“接触”是指将组合物施用于受污染的表面。
“污染”在本文中用于描述微生物入侵,例如在任何材料中或表面上存在毒素或病原体,如细菌、真菌或病毒。
本文所用的“受控释放”是指使用一种材料来调节另一种物质的释放。
本文所用的“有效量”是指本文所公开的组合物的量,在达到所需结果所需的剂量和时间内有效。
本文所用的“环境友好型”是指对环境危害最小的绿色、有机或天然组分。
本文所用的“赋形剂”包括可能包括在微粒中或微粒上的任何其他化合物,其不是治疗或生物活性化合物。因此,赋形剂应该是药学上或生物学上可接受的或相关的(例如,赋形剂通常应该对受试者无毒)。“赋形剂”包括单一的此类化合物,也旨在包括多种赋形剂。
本文所用的“微生物学的”是指包含任何有害微生物(如霉菌(mold)、霉变菌(mildew)、病毒或细菌污染)或其生长。
此处使用的“微生物计数”是指任何表面上存在的微生物污染物的量或数目。
“任选”或“任选地”是指随后描述的事件或情况可能发生或可能不发生,该描述包括事件或情况发生的实例和不发生的实例。
“初级抗微生物剂”在本文中是指对微生物污染物具有生物活性的组合物。
“原发病原体”在本文中是指霉菌、霉变菌、细菌、真菌、病毒或其他可能导致表面污染的微生物。
“足够的量”和“足够的时间”是指实现所需的一种或多种结果所需的量和时间,例如控制和/或预防微生物污染。
本文使用的“表面”是指含有微生物污染的物体。“表面”一词可以应用于整个物体、物体的一部分或一层,以及下至物体的分子结构。
除非另有相反规定,否则组分的“重量百分比”是基于包含该组分的制剂或组合物的总重量。
详细说明
提供了外用滋养/抗微生物组合物。组合物的实施方案包括抗微生物剂,例如季铵化合物和磷酸钙颗粒,其中组合物可任选地包括一种或多种皮肤滋养剂。组合物的实施方案包括乳液和清洁剂。还提供了制备和使用所述组合物的方法。
在更详细地描述本发明之前,应当理解,本发明不限于所描述的特定实施方案,因为这当然可以变化。还应理解,此处使用的术语仅用于描述特定实施方案的目的,而不旨在进行限制,因为本发明的范围将仅由所附权利要求限制。
在提供值的范围的情况下,应理解,除非上下文另有明确规定,否则在该范围的上限和下限之间的每一个中间值,至下限的单位的十分之一,与该范围内的任何其他规定值或中间值都包含在本发明内。这些较小范围的上限和下限可以独立地包括在较小范围内,并且也包括在本发明内,受所述范围内任何特别排除的限制。在所述范围包括一个或两个极限的情况下,排除那些包括的极限中的一个或两者的范围也包括在本发明中。
在本文中,一些范围的数值前面加上“约”一词。本文中使用“约”这一术语是为了为其前面的确切数字以及接近或近似于该术语前面的数字提供文字支持。在确定一个数是否接近或近似于具体列举的数时,接近或近似的未列举数可以是在其出现的上下文中提供与具体列举数实质上等同的数。
除非另有定义,否则本文中使用的所有技术和科学术语具有与本发明所属领域的普通技术人员通常理解的含义相同的含义。尽管在本发明的实践或测试中也可以使用与本文所述方法和材料类似或等同的任何方法和材料,但现在描述代表性的说明性方法和材料。
本说明书中引用的所有出版物和专利通过引用并入本文,就好像每个单独的出版物或专利被具体地和单独地指示通过引用并入,并且通过引用并入本文以公开和描述与所引用出版物相关的方法和/或材料一样。任何出版物的引用都是为了其在申请日之前公开的内容,不应被解释为承认本发明无权凭借现有发明提前于该出版物。此外,所提供的出版日期可能与实际出版日期不同,这可能需要独立确认。
应注意的是,如本文和所附权利要求中所使用的,单数形式“一个”、“一种”和“该”包括复数引用,除非上下文另有明确规定。还应当指出,权利要求书的起草可以排除任何任选元素。因此,本声明旨在作为使用与权利要求要素的陈述有关的“单独”、“仅”等排他性术语,或使用“否定”限制的先行依据。
如本领域技术人员在阅读本公开后将显而易见的,在不脱离本发明的范围或精神的情况下,本文所描述和说明的各个实施方案中的每一个都具有分离的组分和特征,这些组分和特征可以容易地与其他几个实施方案中任何一个的特征分离或组合。任何列举的方法都可以按照列举的事件的顺序或逻辑上可能的任何其他顺序来执行。
虽然为了语法流畅性和功能解释,已经或将要描述该装置和方法,但应明确理解的是,除非根据35U.S.C.§112明确规定,否则权利要求不应被解释为必然受到“手段”或“步骤”限制的任何限制,而是应根据等同司法原则赋予权利要求所提供定义的全部含义和等同含义,如果权利要求是根据35U.S.C.§112明确制定的,则应根据35U.S.C.§112赋予权利要求的全部法定等同含义。
外用制剂
如上所述,本发明的各方面包括外用组合物(即制剂),其被配置用于施用于人类受试者的外部部位。本发明的外用组合物用于施用于部位如哺乳动物受试者如人类受试者的角质化皮肤表面。角质化皮肤表面是指受试者的皮肤位置,即动物身体的外部覆盖物或被膜的位置。因为本发明的外用组合物被配制成用于递送到外部位置,所以它们被配制成与它们被施用的外部位置在生理上相容。因此,当与施用它们的目标角质化皮肤表面接触时,一些实施方案的外用组合物不会引起实质性的(如果有的话)生理反应(例如炎症或刺激),这将使外用组合物的使用不适合外用施用。
如上所述,本发明的外用组合物包括:(a)抗微生物剂,例如季铵化合物;(b)磷酸钙组分,例如磷酸钙颗粒,例如磷酸钙颗粒如多孔磷酸钙颗粒,其可以是羟基磷灰石颗粒;和(c)外用递送载体,例如,其包括一种或多种润肤剂,该递送载体可根据外用组合物的性质而变化,例如,其为乳液还是清洁剂。
抗微生物剂
本发明的外用组合物包括抗微生物剂。感兴趣的抗微生物剂包括季铵化合物、氯己定、氯二甲酚、氯氟卡班、氟代沙兰、六氯苯、己基间苯二酚、碘络合物(含碘成分)、碘络合物(醚硫酸铵和失水山梨醇聚氧乙烯醚单月桂酸酯)、碘络合物(烷基芳氧基聚乙二醇的磷酸酯)、壬基苯氧基聚(乙氧基)乙二醇碘、泊洛沙姆-碘络合物、聚维酮碘、恩地氯铵碘络合物、异辛基甲苯氧基乙氧基乙基二甲基苄基氯化铵、苯酚4、仲戊三甲酚、氧氯苯磺酸钠、三溴沙伦、三氯卡班等。在一些情况下,抗微生物剂不是三氯生。在一些情况下,本发明的外用组合物包括季铵化合物。可以存在于本发明实施方案的组合物中的季铵化合物包括但不限于:(C12-C14烷基)(C1-C2二烷基)苄基铵盐、N-(C12-C18烷基)杂芳基铵盐和N-[(C12-C14烷基)(C1-C2二烷基)]杂芳基亚烷基铵盐。(C12-C14烷基)(C1-C2二烷基)苄基铵盐的非限制性实例包括(C12-C14烷基)二甲基苄基氯化铵、(C12-C14-烷基)二甲基苄基溴化铵和(C12-C14-烷基)二甲基苄基硫酸氢铵。N-(C12-C18烷基)杂芳基铵盐的非限制性实例包括鲸蜡基氯化吡啶鎓、鲸蜡基溴化吡啶鎓和鲸蜡基硫化氢吡啶鎓。对于N-(C12-C18烷基)杂芳基铵盐,可以使用其它阴离子。
适用于本发明组合物的季铵化合物的其它实例包括鲸蜡基三甲基氯化铵、硬脂基三甲基氯化铵、异硬脂基三甲基氯化铵、月桂基三甲基氯化铵、山嵛基三甲基氯化铵、十八烷基三甲基氯化铵、椰油基三甲基氯化铵、鲸蜡基三甲基溴化铵、硬脂基三甲基溴化铵、月桂基三甲基溴化铵、异硬脂基月桂基二甲基氯化铵、二鲸蜡基二甲基氯化铵,二硬脂基二甲基氯化铵,二椰油基二甲基氯化铵,葡糖酰胺丙基二甲基羟乙基氯化铵,双[聚氧乙烯(2)]油基甲基氯化铵,十二烷基二甲基乙基氯化铵,辛基二羟乙基甲基氯化铵、三[聚氧乙烯(5)]-硬脂基氯化铵、聚氧丙烯甲基二乙基氯化铵、月桂基二甲基(乙基苄基)氯化铵、山嵛酸酰胺丙基-N,N-二甲基-N-(2,3-二羟丙基)氯化铵,牛油二甲基氨丙基三甲基二氯化铵、苯索氯铵(即季铵盐)和苯扎氯铵。
在一些情况下,季铵化合物是苯扎氯铵,也称为烷基二甲基苄基氯化铵,商品名为Zephiran(以及N-烷基-N-苄基-N,N-二甲基氯化铵;ADBAC;BC50 BC80)。
苯扎氯铵具有以下结构:
存在于组合物中的季铵化合物的量可以变化,在一些情况下,季铵化合物以0.001-5重量%,例如0.05-2重量%,包括0.1-1重量%的量存在。
磷酸钙
本发明的实施方案包括磷酸钙组分。磷酸钙组分可以变化,,其中可以构成磷酸钙组分的磷酸钙化合物包括但不限于:磷酸三钙、磷酸二钙及其二水合物、磷酸一钙及其一水合物、羟基磷灰石、磷酸八钙、无定形磷酸钙等,其中在一些情况下,磷酸钙组分是羟基磷灰石。
在一些情况下,磷酸钙组分以磷酸钙颗粒的形式存在。本发明组合物的实施方案中存在的颗粒可以是多孔磷酸钙颗粒。所谓“多孔”是指颗粒的孔隙率为30%或更多,例如40%或更多,包括50%或更多,其中孔隙率可在30%至85%的范围内,例如40%至70%,包括45%至55%,使用ASTM D 4284-88“Standard Test Method for Determining PoreVolume Distribution of Catalysts by Mercury Intrusion Porosimetry”中所述的汞侵入孔隙率计孔隙率测定方案测定。孔隙率也用“孔容积(ml/g)”来描述,在这种情况下,许多范围为0.1ml/g至2.0ml/g。在一些情况下,颗粒的孔隙率使得其内表面积范围为10m2/g至150m2/g,如20m2/g至100m2/g,包括30m2/g至80m2/g,使用ASTM D3663-03Standard TestMethod for Surface Area of Catalysts and Catalyst Carriers中描述的BET气体吸附表面积测定方案测定。孔径可以变化,在特定情况下范围为2至100nm,如5至80nm,包括10至60nm。此外,颗粒可以具有的堆积密度的范围为0.2g/cm3至0.5g/cm3,例如0.25g/cm3至0.45g/cm3,包括0.3g/cm3至0.4g/cm3。堆积密度可通过使用标准ASTM WK13023——NewDetermination of Tap Density of Metallic Powders by a Constant VolumeMeasuring Method进行测量。
在一些情况下,颗粒是刚性颗粒,其中在一些情况下,该刚性颗粒是均匀的球形形状。所谓“刚性”是指颗粒是坚硬的,因此它们不易变(pliant)。“均匀”是指颗粒的形状没有实质性变化,因此颗粒具有基本相同的球形形状。术语“球形”在其传统意义上是指其表面在所有点与中心基本等距的圆形物体。在某些实施方案中,感兴趣的是直径为50μm或更小,如40μm或更小,30μm或更小,25μm或更小,例如20μm或更小,如10μm或更小,包括5μm或更小的钙颗粒,其中在一些情况下,中值直径为4μm或更小,例如3μm或更小,包括2μm或更小。在某些实施方案中感兴趣的是钙颗粒组合物,其中组合物中所有颗粒成员的中值直径为20μm或更小,如10μm或更小,包括5μm或更小,其中在一些情况下,中值直径为4μm或更小,如3μm或更小,包括2μm或更小。在某些实施方案中感兴趣的是磷酸钙颗粒组合物,其中组合物中所有颗粒的算术平均值或平均值为20μm或更小,如10μm或更小,包括5μm或更小,其中在一些情况下中值直径为4μm或更小,如3μm或更小,包括2μm或更小。关于上述范围,在一些情况下,颗粒的直径为0.01μm或更大,例如0.1μm或更大,如0.5μm或更大,包括1.0μm或更大。
在一些情况下,这些颗粒是化学纯的。所谓化学纯是指颗粒基本上由一种类型的化合物组成,例如钙化合物,例如磷酸钙矿物。作为多孔颗粒,感兴趣的是含钙颗粒,例如由包括钙阳离子和合适阴离子如碳酸根、磷酸根等的分子制成的含钙颗粒。在一些情况下,颗粒是碳酸钙颗粒,诸如但不限于美国专利5292495和7754176中公开的碳酸钙颗粒。在一些情况下,磷酸钙颗粒由磷酸钙组成,如分子式Ca10(PO4)6(OH)2所示。
在一些情况下,颗粒是陶瓷颗粒。所谓陶瓷是指使用一种方法生产的颗粒,该方法包括将颗粒置于高温条件下的步骤,这些条件如下所示。高温可以为200-1000℃、如300-900℃,包括300-800℃。在一些实施方案中,颗粒具有范围为20-200MPa,如50-150MPa,包括75-90MPa的压缩断裂强度,使用SHIMADZU MCT-W500微压缩试验机颗粒强度测定方案测定,其中颗粒在合适的温度下烧结,例如200℃至900℃,例如400℃至900℃,如欧洲专利EP1840661中所述。在一些实施方案中,颗粒是可生物降解的,这意味着颗粒在生理条件下随着时间的推移以某种方式降解,例如溶解。由于这些实施方案的颗粒在生理条件下是可生物降解的,它们至少在pH为5.5或更低,例如5.3或更低,包括5或更低,例如4.9或更低的条件下开始以可检测的速率溶解。
本发明实施方案中使用的均匀、刚性、球形、多孔磷酸钙颗粒可以使用任何方便的方案制备。在一个感兴趣的方案中,通过喷雾干燥浆料来制造颗粒,所述浆料包括多孔磷酸钙(例如羟基磷灰石)晶体(其尺寸范围可为2nm至100nm),以产生均匀的球形的多孔的,例如纳米多孔的磷酸钙颗粒。然后将所得颗粒烧结足以提供机械和化学稳定的刚性球体的时间。在该步骤中,烧结温度可以为100℃至1000℃、如200℃至1000℃、例如300℃至900℃,包括300℃至800℃,时间为1小时至10小时、如2小时至8小时。
在一些情况下,颗粒负载有一种或多种皮肤滋养剂。存在于本发明这些实施方案的递送组合物中的皮肤滋养活性剂-磷酸钙颗粒复合物包括磷酸钙颗粒,例如如上所述的多孔磷酸钙颗粒、例如纳米多孔磷酸钙颗粒,与一种或多种皮肤滋养活性剂缔合。由于颗粒与一种或多种皮肤滋养活性剂缔合,一种或多种皮肤滋养活性剂以某种方式结合到颗粒上。皮肤滋养活性剂可以通过多种不同的缔合形式与颗粒结合,包括但不限于:离子键、共价键、范德华相互作用、氢键相互作用、正相和反相分配相互作用等。因此,颗粒可以被描述为负载有一定量的一种或多种皮肤滋养活性剂。所谓“负载”是指颗粒包括一定量的一种或多种活性剂(换言之,一定量的单一活性剂或者两种或更多种不同的活性剂),其与颗粒一起,例如与颗粒结合或以其他方式缔合。由于活性剂与颗粒结合,当颗粒存在于递送组合物中时,活性剂不会以任何显著的量从该颗粒上解离。与颗粒结合的活性剂组分(由一种或多种不同的活性剂组成)的量可以根据组成该活性剂结合颗粒的特定活性剂而变化,在某些实施方案中为0.01至1000mg/g,例如0.1至750mg/g,包括1至300mg/g活性剂/克颗粒。
当存在时,活性剂与磷酸钙颗粒可逆地缔合。所谓“可逆缔合”是指活性剂在递送到受试者之后从磷酸钙颗粒中释放,例如,在将包括复合物的递送组合物施用到皮肤部位之后。如下面更详细地描述的,复合物的磷酸钙颗粒在酸性条件下降解,如在pH 5或更低的条件下,例如pH 4.9或更低、pH 4.7或更低、pH4.5或更低、PH4.3或更低。当颗粒降解时,它们会释放出它们的活性剂“有效载荷”。角质层(SC)是皮肤最外层,由大约20层细胞组成,厚度为约10μm。SC的pH值随其深度而变化。其最外层的pH值为4.3-7.0,这取决于采样位置或个体的性别。颗粒层附近的pH值上升到7.0左右。这种上升在与SG相邻的SC的最后几层最为显著,如下所示。因此,当本发明的复合物渗透到SC中时,它们降解并同时释放与其缔合的任何活性剂。
释放的活性剂保持其所需的活性,尽管其已与复合物中的磷酸钙颗粒缔合。因此,活性剂与磷酸钙颗粒的结合和释放对活性剂的损害实质上很小(如果有的话)。因此,活性剂的活性不会降低到对其用途产生不利影响的程度,其中,对于给定的活性剂,由与磷酸钙颗粒的缔合引起的活性的任何降低是25%或更小,10%或更小,如5%或更小,包括1%或更小,例如通过活性测定方法测定。
在一些实施方案中,活性剂与复合物中的多孔磷酸钙颗粒的缔合保留了活性剂的一个或多个所需特征,例如稳定性。换言之,与缺乏磷酸钙颗粒的对照相比,复合物稳定了活性剂。
本发明的外用组合物包括一定量的存在于外用递送载体中的磷酸钙颗粒,以及任选的一种或多种皮肤滋养活性剂。如上所述,在一些情况下,磷酸钙颗粒负载有一种或多种皮肤滋养活性剂。在其他情况下,一种或多种皮肤滋养剂以其他方式存在于外用递送载体中。存在于递送组合物中并因此与递送载体结合的磷酸钙颗粒的量可以变化。在某些实施方案中,磷酸钙颗粒在组合物中的存在量为约0.001重量%或更多,例如0.01重量%、或0.05重量%、或1重量%或更多、5重量%或更多、10重量%或更多、15重量%或更多、25重量%或更多、30重量%或更多、50重量%或更多。在一些实施方案中,将磷酸钙颗粒直接添加到递送载体中(即,在与递送载体结合/混合之前不润湿磷酸钙颗粒)。换言之,将磷酸钙颗粒和递送载体结合以形成外用组合物。
外用递送载体
递送载体(即外用递送组分)是指外用组合物中不是磷酸钙颗粒或季铵化合物的那部分。感兴趣的递送载体包括但不限于适合通过外用途径施用的组合物,例如乳液、皂等。在某些实施方案中,配制载体以施用于受试者的外部区域或表面,例如角质化的皮肤表面。主题组合物可以配制为各组分的稳定溶液或悬浮液,例如在水性溶剂中。在需要的情况下,各组分可以与一种或多种载体材料组合,以根据需要形成溶液、悬浮液、凝胶、乳液、乳霜、软膏、气溶胶喷雾、滚涂、泡沫产品、慕斯等。在一些实施方案中感兴趣的是含水递送载体,即包括一定量水的含水载体。含水载体的实例包括水凝胶载体、喷雾剂、血清等。
外用组合物还可以包含其他生理上可接受的赋形剂或其他次要添加剂,特别是与感官特性相关的,例如香料、染料、缓冲剂、冷却剂(例如薄荷醇)、涂敷材料等。赋形剂和次要添加剂将以常规量存在,例如,按重量计,在约0.001%-5%的范围内,如0.001-2%,在一些情况下不超过总计10重量%。
感兴趣的乳液和清洁剂(以及其他外用制剂)可包括以下一种或多种组分:水、粘度调节剂、保湿剂(如丙二醇)倒钩(barb)、植物油和氢化植物油、润肤剂、调理剂、乳化剂、脂肪酸甘油酯、硅酮、糖的C1-C30单酯和聚酯、调理剂、防腐剂等。根据外用制剂,感兴趣的其他组分包括:研磨剂、吸收剂、抗微生物和抗真菌剂、收敛剂、抗痤疮剂、防皱剂、抗氧化剂、抗微生物剂、粘合剂、生物活性剂、缓冲活性剂、膨胀剂活性物质、螯合剂、化学添加剂、外用止痛药、成膜剂、遮光剂、pH调节剂、还原剂、着色剂、香料、化妆品舒缓剂、晒黑活性物质和加速剂、皮肤美白/增白剂、防晒霜、表面活性剂、皮肤调理剂,例如植物(例如但不限于:洋甘菊(母菊)花提取物、芦荟叶汁)、维生素(例如生育酚乙酸酯(维生素e))等。如上所述,在某些实施方案中感兴趣的是半固体递送组合物,例如凝胶、乳霜和软膏。这样的组合物可以是(除了活性剂之外)水、水溶性聚合物、防腐剂、醇、多价醇、乳化剂、蜡、溶剂、增稠剂(包括但不限于羟乙基纤维素)、增塑剂、pH调节剂、保水剂等的混合物。此外,这样的组合物还可以含有其他生理上可接受的赋形剂或其他次要添加剂,例如香料、染料、缓冲剂、涂料等。
润肤剂是一种替代或添加皮肤中脂质和天然油脂的化合物。本文中使用的术语润肤剂旨在包括传统的脂质材料(例如脂肪、蜡和其他不溶于水的材料)、极性脂质(例如,已被改性以使其更水溶的脂质材料)、硅酮和碳氢化合物。感兴趣的润肤剂包括但不限于:己二酸二异丙酯、肉豆蔻酸异丙酯、棕榈酸异丙酯,棕榈酸乙基己酯,新戊酸异癸酯,C12-15醇苯甲酸酯,马来酸二乙基己酯、PPG-14丁基醚、PPG-2肉豆蔻醚丙酸酯、Di-PPG-3肉豆蔻醚己二酸酯、蓖麻油酸鲸蜡酯、硬脂酸胆固醇酯、异硬脂酸胆固醇酯、乙酸胆固醇酯、荷荷巴油、可可脂、乳木果油、羊毛脂和羊毛脂酯。
硅油可分为挥发性和非挥发性两类。本文中使用的术语“挥发性”是指在环境温度下具有可测量蒸汽压的材料。感兴趣的挥发性硅油包括但不限于:含有3-9个,例如4-5个硅原子的环状或线性聚二甲基硅氧烷。线性挥发性硅酮材料在25℃下的粘度可为5厘沲或更低,而环状材料的粘度可为10厘沲或更低。感兴趣的非挥发性硅油包括但不限于:聚烷基硅氧烷、聚烷基芳基硅氧烷和聚醚硅氧烷共聚物。感兴趣的基本上非挥发性的聚烷基硅氧烷包括,例如,在25℃下粘度为5-100000厘沲的聚二甲基硅氧烷。
合适的酯包括但不限于:具有10-20个碳原子的脂肪酸的烯基或烷基酯,例如棕榈酸异丙酯、异硬脂酸异丙酯,异壬酸异壬酯、肉豆蔻酸油酯、硬脂酸油酯和油酸油酯;醚酯,例如乙氧基化脂肪醇的脂肪酸酯;多元醇酯;乙二醇单脂肪酸酯和二脂肪酸酯;二甘醇单脂肪酸酯和二脂肪酸酯、聚乙二醇(100-6000)单脂肪酸酯或二脂肪酸酯;丙二醇单脂肪酸酯和二脂肪酸酯,如聚丙二醇2000单油酸酯、聚丙二醇2000-单硬脂酸酯、乙氧基化丙二醇单硬脂酸酯;甘油单脂肪酸酯和二脂肪酸酯;甘油硬脂酸酯&PEG-100硬脂酸酯;聚甘油多脂肪酯,如乙氧基化甘油单硬脂酸酯、1,3-丁二醇单硬脂酸酯和1,3-丁二醇二硬脂酸酯;二醇二硬脂酸酯、聚氧乙烯多元醇脂肪酸酯;失水山梨醇脂肪酸酯;聚氧乙烯失水山梨醇脂肪酸酯是令人满意的多元醇酯;蜡酯如蜂蜡、鲸蜡、肉豆蔻酸肉豆蔻酯、硬脂酸硬脂酯;甾醇酯,其中大豆甾醇和胆甾醇脂肪酸酯是其实例。这些化合物的植物来源和动物来源都可以使用。这类油的实例包括但不限于:蓖麻油、羊毛脂油、C10-18甘油三酯、辛酸/癸酸甘油三酯、甜杏仁油、杏仁油、芝麻油、荠蓝油(camelina sativa oil)、罗望子油(tamanu seed oil)、椰子油、玉米油、棉籽油、亚麻籽油、油墨油(ink oil)、橄榄油、棕榈油、东印度山榄科植物脂、菜籽油、大豆油、葡萄籽油、向日葵籽油、胡桃油等。还合适的是合成或半合成甘油酯,如脂肪酸甘油单-、二-和三酯,它们是经过改性的天然脂肪或油,例如多元醇如甘油的单-、双-或三酯。在一个实例中,脂肪(C12-22)羧酸与一个或多个重复的甘油基反应。硬脂酸甘油酯、二异硬脂酸二甘油酯、聚甘油-3异硬脂酸酯、聚甘油-4异硬脂酸酯,聚甘油-6蓖麻油酸酯、二油酸甘油酯、二异硬脂酸甘油酯、四异硬脂酸甘油酯、三辛酸甘油酯、双硬脂酸二甘油酯、亚油酸甘油酯、肉豆蔻酸甘油酯,异硬脂酸甘油酯、PEG蓖麻油、PEG甘油醚油酸酯,PEG甘油醚硬脂酸酯和PEG甘油醚牛油酸酯。
感兴趣的脂肪酸包括但不限于:那些具有10至30个碳原子的脂肪酸,例如天竺葵酸、月桂酸、肉豆蔻酸、棕榈酸、硬脂酸、异硬脂酸、羟基硬脂酸、油酸、亚油酸、蓖麻油酸、花生酸、山萮酸和芥酸。
多元醇类型的保湿剂也可用于组合物中,其中多元醇的实例包括但不限于:丙三醇(也称为甘油)、聚亚烷基二醇、亚烷基多元醇及其衍生物,包括丙二醇、二丙二醇、聚丙二醇、聚乙二醇及其衍生物、山梨醇、羟丙基山梨醇、己二醇、1,3-丁二醇、1,2,6-己三醇、乙氧基化甘油、丙氧基化甘油及其混合物。还感兴趣的是糖,例如葡萄糖、果糖、蜂蜜、氢化蜂蜜、肌醇、麦芽糖、甘露醇、麦芽糖醇、山梨醇、蔗糖、木糖醇、木糖等。当存在时,保湿剂的量可在0.001至25%的范围内,例如约0.005至20%,包括约0.1至15%,其中在一些情况下,保湿剂的量在组合物重量的0.5至30%的范围内,例如1至15%。
乳化剂也可以存在于载体组合物中。当存在时,乳化剂的总浓度可为总组合物重量的0.01至40%,例如1至20%,包括1至5%。感兴趣的乳化剂包括但不限于:阴离子、非离子、阳离子和两性活性剂。感兴趣的非离子表面活性剂包括具有C10-C20脂肪醇或酸疏水物(与约2-约100摩尔环氧乙烷或环氧丙烷每摩尔疏水物缩合)的那些;与2-20摩尔环氧烷缩合的C2-C10烷基酚;乙二醇的单脂肪酸酯和二脂肪酸酯;脂肪酸单甘油酯;失水山梨醇、单-和二-C8-C20脂肪酸;聚氧乙烯失水山梨醇及其组合。烷基糖苷和糖脂肪酰胺(例如甲基葡萄糖酰胺)也是感兴趣的非离子乳化剂。感兴趣的阴离子乳化剂包括皂、烷基醚硫酸盐和磺酸盐、烷基硫酸盐和磺酸盐、烷基苯磺酸盐、烷基和二烷基磺基琥珀酸盐、C8-C20酰基羟乙基磺酸盐、C8-C20烷基醚磷酸盐、烷基醚羧酸盐及其组合。
在需要的情况下,组合物中可以包括防腐剂,例如,以防止潜在有害微生物的生长。感兴趣的防腐剂包括对羟基苯甲酸的烷基酯、乙内酰脲衍生物、丙酸盐和各种季铵化合物。感兴趣的特定防腐剂包括但不限于:氨基甲酸碘丙炔丁酯、苯氧乙醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、咪唑烷基脲、脱氢乙酸钠、苄醇、苄基半缩甲醛、对羟基苯甲酸苄酯、5-溴-5-硝基-1,3-二恶烷、2-溴-2-硝基丙烷-1,3-二醇、辛甘醇、乙基己基甘油、苯氧基乙醇山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、对羟基苯甲酸乙酯、对羟基苯甲酸丁酯、苯甲酸钠、山梨酸钾、乙二胺四乙酸二钠盐、氯二甲酚、DMDM乙内酰脲、氨基甲酸3-碘-2-丙基丁酯、二葡糖酸洗必泰、苯氧乙醇,二偶氮烷基脲,双胍衍生物,苯甲酸钙,丙酸钙,辛甘醇,双胍衍生物,克菌丹,二乙酸洗必泰,二葡糖酸洗必泰、二盐酸洗必泰;氯乙酰胺,三氯生,氯丁醇,对氯间甲酚,氯苯,氯代百里酚,氯二甲酚、间甲酚,邻甲酚,DEDM乙内酰脲,二月桂酸DEDM乙内酰脲,脱氢乙酸,二唑烷基脲、双溴丙脒二羟乙基磺酸盐、DMDM乙内酰脲、甲基异噻唑啉酮/甲基氯异噻唑啉酮、1,2-己二醇&辛甘醇等。当存在时,防腐剂可以以组合物重量的约0.01%至约10%的量存在于递送组合物中。在一些情况下,组合物不含对羟基苯甲酸酯。
递送组合物中可以包括增稠剂或粘度调节剂。感兴趣的增稠剂包括但不限于:多糖,如淀粉、天然/合成树胶和纤维素等。感兴趣的淀粉包括但不局限于化学改性的淀粉,如辛烯基琥珀酸铝淀粉。感兴趣的树胶包括但不限于:黄原胶、菌核、果胶、刺梧桐树胶、阿拉伯树胶、琼脂、瓜尔胶(例如,胍尔豆(瓜尔)树胶、卡拉胶、藻酸盐及其组合。合适的纤维素包括但不限于:羟丙基纤维素、羟丙基甲基纤维素、羟乙基纤维素、乙基纤维素和羧甲基纤维素钠。合成聚合物仍然是另一类有效的增稠剂。这一类别包括交联聚丙烯酸酯,如卡波姆和聚丙烯酰胺,如305;聚丙烯酰胺&C13-14异烷烃&月桂基聚氧乙烯(7)醚等。当存在时,增稠剂的量可以在0.001-5%的范围内,例如0.1-2%。
在一些情况下,可以存在天然或合成的有机蜡,例如一种或多种天然或合成蜡,例如动物蜡、植物蜡或矿物蜡。在一些情况下,此类蜡的熔点范围为20至150℃,如30至100℃,包括35至75℃。此类蜡的示例包括蜡如聚乙烯或合成蜡;或各种植物蜡,如杨梅、小烛树蜡、地蜡、金合欢、蜂蜡、不定形蜡、鲸蜡酯、花蜡、柑橘蜡、巴西棕榈蜡、西蒙得木蜡、野漆树蜡、聚乙烯、微晶蜡、米糠、羊毛脂蜡、貂、褐煤蜡、杨梅、小冠巴西棕蜡、地蜡、棕榈仁蜡、石蜡、鳄梨蜡、苹果蜡、紫胶蜡、鼠尾草蜡(clary wax)、废谷物蜡、葡萄蜡及其聚亚烷基二醇衍生物,如PEG6-20蜂蜡或PEG-12巴西棕榈蜡;或脂肪酸或脂肪醇,包括它们的酯,例如羟基硬脂酸(例如12-羟基硬脂酸)、三硬脂酸甘油酯和三山萮酸甘油酯(tribehenin)。同样令人感兴趣的还有格鲁椰子籽脂、杏仁脂、芦荟脂、杏子仁脂、摩洛哥坚果脂、马里帕棕榈籽脂、鳄梨脂、巴巴苏脂、巴库里脂、巴古拉软脂、猴面包树软脂、油拔树籽脂、阔叶雾冰藜籽脂、黑加仑籽脂、巴西坚果脂、山茶花脂、山竹花脂、坎德拉脂、卡纳巴脂、巴西大风子籽脂、洋甘菊脂、可可脂、椰子脂,咖啡脂、棉质软脂、蔓越莓脂、古朴阿苏果脂、葡萄籽脂、榛子籽脂、大麻籽脂、马尾草脂、lllipe脂、野生芒果果仁脂、荷荷巴油异构化脂、牛油果脂、烛果脂、夏威夷核脂、薰衣草脂、柠檬脂、酸橙脂、澳洲坚果脂、芒果脂、马鲁拉脂、莫诺伊脂(Monoi Butter)、雾冰黎脂、穆卡贾脂(Mucaja Butter)、巴西棕榈乳脂、齐墩果脂(Olea butter)、橄榄脂、橙脂、棕榈油,百香果脂,府华脂(Phulwara Butter),开心果脂,石榴脂、南瓜脂、树莓脂、大米脂、加盐奶油(Sal Butter)、巴西卡波特罗奇脂(Sapucainha butter)、调味黄油(Seasamebutter)、牛油树脂、大豆黄油琼崖海棠脂、向日葵籽脂、甜杏仁脂、大红桔脂、Tucuma种子黄油、黄腊树脂(Ucuuba Butter)和小麦胚芽脂。
本发明的外用组合物可以包括表面活性剂(表面活性剂)。表面活性剂是指一种降低表面张力并促进皮肤清洁的成分。许多表面活性化合物也起乳化剂的作用,例如蜡或发泡剂。表面活性剂主要有四类:阳离子、阴离子、两性和非离子。两性表面活性剂和非离子表面活性剂通常对表皮的耐受性最好。
表面活性剂C特别包括聚氧乙烯月桂基醚硫酸铵;月桂基硫酸铵;辛酰/癸酰基葡糖苷;鲸蜡基甜菜碱;椰油酰胺丙基甜菜碱;椰油基甜菜碱;椰油基葡糖苷;癸基葡糖苷;N-(椰油酰胺基乙基)-N-(2-羟基乙基氨基)-2-羟基二乙酸二钠(disodiumcocoamphodiacetate);月桂基聚氧乙烯醚磺基琥珀酸二钠;月桂基磺基琥珀酸二钠;硬脂酰谷氨酸二钠;乙二醇硬脂酸酯;月桂酰胺丙基甜菜碱;PEG-100硬脂酸酯;鲸蜡基磷酸钾;N-(椰油酰胺基乙基)-N-(2-羟基乙基氨基)-2-羟基乙酸钠(sodiumcocoamphoacetate);椰油基羟基乙磺酸钠;月桂基聚氧乙烯醚硫酸钠;月桂基硫酸钠;棕榈仁油酸钠(Sodium palm kernelate);甲基椰油酰基月桂酸钠;α-烯烃磺酸盐如C14-C16α-烯烃磺酸钠;月桂酰甲基羟乙基磺酸钠;椰油酰胺丙基氢磺基甜菜碱(cocamidopropylhydrosultaine);月桂酰基肌氨酸钠;椰油基谷氨酸钠;椰油基甘氨酸钠;月桂酰乳酸钠;烷基葡糖苷;烷基聚葡糖苷;辛酸/癸酸葡糖苷月桂基醚;失水山梨醇聚氧乙烯醚月桂酸酯如失水山梨醇聚氧乙烯醚(80)月桂酸酯、失水山梨醇聚氧乙烯醚(20)月桂酸酯;甲基磺基月桂酸钠;月桂基磺基乙酸钠;磺基月桂酸二钠;皂,其为脂肪酸盐,具有通式RCOOM(R=具有多于10个碳原子的长烃链,M=金属、碱金属或有机碱)。根据M基团的性质,存在碱金属皂(Na+、K+、NH4+皂)、金属皂(特别是钙)和有机皂(例如三乙醇胺皂,包括硬脂酸三乙醇胺)及其组合。有利地,表面活性剂选自阴离子表面活性剂、两性表面活性剂和非离子表面活性剂及其组合。有利地,该制剂包含相对于其总重量2-25重量%的表面活性剂。
递送组合物中还可以包括着色剂、香料和研磨剂。这些物质各自可以在0.05-5重量%的范围内,例如0.1-3重量%。感兴趣的着色剂包括二氧化钛,在适当的情况下进行表面处理(编码在参考CI 77891的颜色指数中)、锰紫(CI 77742)、群青蓝(CI 77007)、氧化铬(CI 77288)、水合氧化铬(CI77289)、铁蓝(CI 77510)、氧化锌、二氧化锆。感兴趣的具体着色剂包括:D&C红19号(CI 45170)、D&C红9号(CI 15585)、D&C红21号(CI 45380)、D&C橙4号(CI 15510)、D&C橙5号(CI 45370)、D&C红27号(CI 45410)、D&C红13号(CI 15630)、D&C红7号(CI 15850:1)、D&C红6号(CI 15850:2)、D&C黄5号(CI 19140)、D&C红36号(CI 12085)、D&C橙10号(CI 45425)、D&C黄6号(CI 15985)、D&C红30号(CI 73360)、D&C红3号(CI 45430)、炭黑(CI 77266)、胭脂虫红色淀(CI 75470)、天然或合成黑色素和铝色淀。
感兴趣的香料包括:欧洲冷杉叶油、乙醛、N-乙酰苯胺、乙酸、欧蓍草油、猕猴桃果水、己二酸、琼脂、变性酒精、藻酸铵、库拉索芦荟叶、乙酸戊酯、苯甲酸戊酯、戊基肉桂醛、茴香脑、茴香醇、洋甘菊花水、苯甲醛、苯甲醇、白桦油、齿叶乳香树油、乙酸丁酯、乳酸丁酯、金盏花花油、山茶叶水、樟脑、辣椒素、雪松醇、肉桂醛、柠檬醛、香茅醇、柑橘(莱姆)油、柑橘(橙)油、柚子(葡萄柚)油、柑桔(橘子)皮油、香豆素、二丙酮醇、肉桂酸乙酯、乙醚、石竹(丁香)花油、法尼醇、佛罗里达栀子油、马齿苋油、己基肉桂醛、氢化松香、八角茴香油、乙酸异戊酯、墨西哥杜松油、月桂油、薰衣草油、互叶千层(茶树)叶油、梅丽莎叶油、薄荷油、薄荷脑、2-萘酚、牛至叶油、人参根提取物、壬酸、香叶天竺葵花油、银松锥油、杏仁油、罗莎花油、迷迭香叶油、檀香油、百里香油、香兰素、葡萄叶油、姜根油、。
在一些情况下,所述组合物可以包括三氯生。发现该制剂中使用的试剂对所有属的微生物有效,(例如:细菌、真菌、铜绿假单胞菌、卡氏假单胞杆菌、金黄色葡萄球菌、大肠杆菌、白色念珠菌、黑曲霉、鼠伤寒沙门氏菌等)。
本发明实施方案的外用组合物不含抗微生物量的消毒酒精,例如乙醇或异丙醇。如果存在酒精,则其存在量为30%或更少,例如25%或更少,包括20%或更少。在一些情况下,组合物是不含酒精的。在一些情况下,组合物可以包括一定量的调节酒精,例如鲸蜡醇、硬脂醇、鲸蜡硬脂醇等。
用途
本发明的外用制剂可用于各种应用中。例如,本发明的乳液和清洁剂可用于需要皮肤营养和消毒的应用中。
在实施本发明的方法中,将外用组合物施用于受试者的外部区域,并在该外部区域维持一段足以产生所需结果的时间,例如,如上所述的皮肤滋养和/或清洁/消毒。在一些实施方案中,外部区域是角质化的皮肤区域。角质化的皮肤区域,包括毛囊、汗腺和皮脂腺,可以存在于各种位置,例如四肢、手臂、腿;躯干,例如胸部、背部、胃部;头部,例如颈部、面部;等。在一些实施方案中,所述区域是头部区域,例如面部区域,例如前额、枕部区域、口腔周围等。施用所述组合物的外部区域的面积可变化,在一些实施方案中范围为1mm2-20000cm2或更大,例如1-50cm2,包括3-10cm2。
施用后,将外用制剂在施用部位维持足以产生所需治疗结果的时间,例如,改善感兴趣的症状,减少干燥。时间可以变化,并且在一些实施方案中,其范围从瞬间到几天,例如10秒到1分钟到24小时或更长,例如30分钟到12小时,包括1小时到12小时或更长。
根据制剂,施用后可进行洗涤,例如,外用组合物为清洁剂的情况下。
本主题的方法和组合物可用于各种不同种类的动物,其中动物通常是“哺乳动物”或“哺乳动物”,其中这些术语被广泛用于描述哺乳动物类内的生物,包括食肉目(如狗和猫)、啮齿目(如小鼠、豚鼠和大鼠)、兔形目(如兔子)和灵长类(如人类、黑猩猩和猴子)。在某些实施方案中,受试者或患者是人类。
受试者外用制剂可用于需要滋养和/或清洁/消毒受试者的外部位置的施用中。
当经处理的皮肤的皱纹、粗糙度、干燥度、松弛度、灰黄或色素斑点的量显著减少时,实施本发明的方法可以改善皮肤。测量皮肤状况改善的方法在本领域中是公知的(参见例如Olsen等人,J.Amer.Acad.Dermatol.26:215-24,1992),可以包括由患者或第二方如治疗医生进行的主观评估。客观方法可以包括皮肤形貌测量,例如Grove等人,J.Amer.Acad.Dermatol.21:631-37(1989)中描述的那些。在皮肤形貌测量中,硅橡胶复制品由小面积的皮肤制成,例如直径为1cm的圆形区域。硅橡胶复制品可以捕捉皮肤上的细纹和皱纹。然后使用计算机数字图像处理对这些样本进行分析,以提供皮肤形貌的客观测量。在数字图像处理之后生成的皮肤形貌测量可以使用值Ra和Rz来测量,如Olsen等人,J.Amer.Acad.Dermatol.37:217-26,1997中所述,其中Ra表示平均中心线上方和下方的皮肤表面特征的偏差面积,Rz表示皮肤表面轮廓的五个相等区段中的最大高度和最小高度之间的差。与未处理的皮肤相比,根据本发明处理的皮肤中Ra和Rz值的统计学显著下降(例如,P<0.05)表明皮肤的改善,这是通过实践本发明的方法实现的。
提供以下实施例是为了说明而非限制。
实验
一、抗菌清洁剂组合物
A.制剂1
1.范围
B.制剂2
1.范围
B.有益效果
经常洗手是防止微生物感染的最佳方法,但可能会导致皮肤干燥和受损。上面报道的抗微生物清洁剂是设计用于频繁使用而不会产生干燥效果的液体洗手液和沐浴露制剂。它们舒适光滑,富含保湿营养,能杀死99.9%的细菌,让双手柔软干净。
持续每天使用,皮肤状况有望在一周内得到明显改善。
有益效果:
通过加速屏障恢复快速再生新皮肤细胞
刺激成纤维细胞产生弹性蛋白和胶原蛋白
帮助修复受损皮肤
改善角质层的完整性
增加柔韧性和肌肤活力
减少细纹和皱纹的出现
舒缓和治愈烧伤和小皮肤擦伤”
其他产品特征:
不含香料
低致敏性认证-对所有皮肤类型和年龄都安全
天然,95%以上基于蔬菜
无动物副产品
其他用途:
预防和消除防护手套刺激
预防和消除口罩刺激,“maskne”
预防和修复消毒/防腐酒精(如异丙醇/乙醇)损伤的皮肤
消除皮炎、湿疹和尿布疹
消除身体粉刺和粉刺
多用途杀菌和舒缓-小烧伤、割伤和擦伤
消除顽固气味(脚部和身体)
消除皮肤干燥状况、风化、开裂或鳞屑状皮肤
消炎
防腐和治疗:用于纹身和皮肤擦伤
每天使用无刺激、不干燥的消毒液,可在数小时内杀死99.9%的微生物,同时改善皮肤状况。
II、保湿剂
A.制剂1
1.范围
B.制剂2
1.范围
B.有益效果
上述抗微生物保湿剂可杀死皮肤上99.9%的微生物,并在数小时内持续抵御新细菌,同时补水、滋养和改善皮肤状况。
上述抗微生物保湿剂可提供4小时以上的消毒保护,同时将保湿营养素递送到皮肤中,使营养素从内而外发挥作用,保护和改善皮肤健康。
·施用后4个多小时有效
·自信地安全接触公共表面
·防腐/消毒不含酒精和香料
·有助于消除皮肤干燥状况
·经认证的低致敏性;非敏化剂
·对所有年龄段和皮肤类型都安全;无刺激性
·无动物副产品;
持续每天使用,皮肤状况有望在一周内得到明显改善。抗菌活性成分可杀死99.9%的微生物(细菌、病毒和真菌),并保留在皮肤表面,提供持久的消毒保护,防止新细菌滋生。
在至少一些先前描述的实施方案中,在一个实施方案中使用的一个或多个元素可以可互换地在另一个实施方案中使用,除非这样的替换在技术上不可行。本领域技术人员应当理解,在不脱离所要求保护的主题的范围的情况下,可以对上述方法和结构进行各种其他省略、添加和修改。所有这样的修改和改变旨在落入由所附权利要求限定的主题的范围内。
本领域技术人员应当理解,一般来说,本文中使用的术语,尤其是所附权利要求(例如,所附权利要求的主体)中使用的术语通常旨在作为“开放”术语(例如,术语“包括”应解释为“包括但不限于”,术语“具有”应解释为“至少具有”,术语“包含”应解释为“包含但不限于”,等等)。本领域技术人员还应当理解,如果意图是特定数目的引入的权利要求叙述,那么将在权利要求中明确地叙述这样的意图,并且在没有这样的叙述的情况下,不存在这样的意图。例如,为了帮助理解,以下所附权利要求可以含有使用介绍性短语“至少一个”和“一个或多个”来引入权利要求叙述。然而,此类短语的使用不应被解释为暗示,通过不定冠词“一”或“一个”引入权利要求叙述将含有此类引入的权利要求叙述的任何特定权利要求限制为仅包含一个此类叙述的实施方案,即使当同一权利要求包括介绍性短语“一个或多个”或“至少一个”以及不定冠词如“一”或“一个”(例如,“一”和/或“一个”应解释为表示“至少一个”或“一个或多个”);这同样适用于使用定冠词来引入权利要求叙述的情况。另外,即使明确记载了所引入的权利要求叙述的具体数目,本领域技术人员将认识到,这样的叙述应当被解释为至少表示所叙述的数目(例如,不带其他修饰语的单纯叙述“两个叙述物”是指至少两个叙述物,或者两个或更多个叙述物)。此外,在使用类似于“A、B和C等中的至少一个”的惯例的那些情况下,一般来说,这样的构造意在为本领域技术人员将理解该惯例的意涵(例如,“具有A、B和C中的至少一个的系统”将包括但不限于以下系统:单独A、单独B、单独C、A和B一起、A和C一起、B和C一起、和/或A、B和C一起等)。此外,在那些使用类似于“A、B或C等中的至少一个”的惯例的情况下,一般来说,这样的构造意在为本领域技术人员将理解惯例的意涵(例如,“具有A、B或C中的至少一个的系统”将包括但不限于以下系统:单独A、单独B、单独C、A和B一起、A和C一起、B和C一起、和/或A、B和C一起等)。本领域技术人员还应理解,实际上任何呈现两个或多个备选术语的转折词和/或短语,无论是在说明书、权利要求书还是附图中,都应被理解为考虑包括术语之一、任一项术语或两项术语的可能性。例如,短语“A或B”将被理解为包括“A”或“B”或“A和B”的可能性。
另外,在根据马库什组描述本公开内容的特征或方面的情况下,本领域技术人员将认识到,本公开内容也因此根据马库什组的任何个体成员或成员子组来描述。
如本领域技术人员将理解的,出于任何和所有目的,例如就提供书面描述而言,本文公开的所有范围还涵盖任何和所有可能的子范围及其子范围的组合。任何列出的范围可以容易地被认为是充分描述的并且使得相同的范围能够被分解成至少相等的一半、三分之一、四分之一、五分之一、十分之一等。作为非限制性示例,本文讨论的每个范围可以容易地分解为下三分之一、中三分之一和上三分之一等。如本领域技术人员还可以理解的,所有诸如“直到”、“至少”、“大于”、“小于”和类似的语言包括所列举的数字并指随后可被分解为如上所述的子范围的范围。最后,如本领域技术人员将理解的,范围包括每个单独的成员。因此,例如,具有1-3个物品的组是指具有1、2或3个物品的组。类似地,具有1-5个物品的组是指具有1、2、3、4或5个物品的组,诸如此类。
因此,前述内容仅说明本发明的原理。应当理解,本领域技术人员将能够想到各种布置,尽管本文没有明确描述或示出,但是这些布置体现了本发明的原理并且被包括在其精神和范围内。此外,本文记载的所有示例和条件语言主要旨在帮助读者理解本发明的原理以及发明人为促进本领域而贡献的概念,并且应被解释为不限于此类具体记载的示例和条件。此外,本文中记载本发明的原理、方面和实施方案及其具体示例的所有陈述旨在涵盖其结构和功能等同物。另外,这样的等同物旨在包括当前已知的等同物和未来开发的等同物,即,无论结构如何,所开发的执行相同功能的任何元素。此外,本文所公开的任何内容均不旨在献给公众,无论此类公开内容是否在权利要求中明确记载。
因此,本发明的范围并不旨在限于本文所示和描述的示例性实施方案。相反,本发明的范围和精神由所附权利要求体现。在权利要求中,35U.S.C.§112(f)或35U.S.C.§112(6)被明确定义为仅当确切的短语“用于……的装置(means for)”或确切的短语“用于……的步骤(step for)”记载于权利要求中的某限定的开头时才被援引用于权利要求中的此类限定;如果权利要求中的限定中未使用此类确切的短语,则不援引35U.S.C.§112(f)或35U.S.C.§112(6)。
Claims (19)
1.一种外用组合物,包括:
非三氯生抗微生物剂;
磷酸钙组分;和
外用递送载体。
2.根据权利要求1所述的外用组合物,其中所述抗微生物剂包括季铵化合物。
3.根据权利要求2所述的外用组合物,其中所述季铵化合物为苯扎氯铵。
4.根据前述权利要求中任一项所述的外用组合物,其中所述磷酸钙组分包括磷酸钙颗粒。
5.根据权利要求4所述的外用组合物,其中所述磷酸钙颗粒的分子式为Ca10(PO4)6(OH)2。
6.根据前述权利要求中任一项所述的外用组合物,其中所述磷酸钙组分包括羟基磷灰石。
7.根据前述权利要求中任一项所述的外用组合物,其中所述组合物进一步包括至少一种润肤剂。
8.根据前述权利要求中任一项所述的外用组合物,其中所述组合物进一步包括一种或多种皮肤滋养剂。
9.根据前述权利要求中任一项所述的外用组合物,其中所述组合物进一步包括防腐剂。
10.根据权利要求9所述的外用组合物,其中所述防腐剂组分包括对羟基苯甲酸酯。
11.根据权利要求9所述的外用组合物,其中所述防腐剂组分包括三氯生。
12.根据权利要求9所述的外用组合物,其中所述防腐剂组分不含对羟基苯甲酸酯。
13.根据前述权利要求中任一项所述的外用组合物,其中所述外用组合物是清洁剂。
14.根据权利要求13所述的外用组合物,其中所述外用组合物包括表面活性剂。
15.根据权利要求1至12中任一项所述的外用组合物,其中所述外用组合物是乳液。
16.一种方法,包括将根据前述权利要求中任一项所述的外用组合物施用到受试者的皮肤表面。
17.根据权利要求16所述的方法,其中所述方法是清洁所述受试者的皮肤表面的方法。
18.根据权利要求16所述的方法,其中所述方法是对受试者的皮肤表面进行保湿的方法。
19.一种制备根据权利要求1至15中任一项所述的外用组合物的方法。
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KR (1) | KR20240118064A (zh) |
CN (1) | CN118076335A (zh) |
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US6096324A (en) * | 1995-06-13 | 2000-08-01 | Laboratory Skin Care | Methods of delivering materials into the skin, and compositions used therein |
US7754770B2 (en) * | 2005-06-27 | 2010-07-13 | Mason Chemical Company | Antimicrobial composition |
WO2010050980A1 (en) * | 2008-10-31 | 2010-05-06 | Laboratory Skin Care, Inc. | Topical formulations comprising hydroxyapatite particles for stimulation and maintenance of collagen fibers |
US9693564B2 (en) * | 2011-06-21 | 2017-07-04 | Safehands Solutions, LLC | Water based antimicrobial composition using benzalkonium chloride and cocamidopropyl PG-dimonium chloride phosphate |
US20210274780A1 (en) * | 2020-03-06 | 2021-09-09 | Sarfaraz K. Niazi | Disinfectant Composition Against the Novel Wuhan Corona Virus COVID-19 |
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