WO2016150309A1 - 包含瓣蕊唐松草的组合物及其用于皮肤增亮的用途 - Google Patents

包含瓣蕊唐松草的组合物及其用于皮肤增亮的用途 Download PDF

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WO2016150309A1
WO2016150309A1 PCT/CN2016/076204 CN2016076204W WO2016150309A1 WO 2016150309 A1 WO2016150309 A1 WO 2016150309A1 CN 2016076204 W CN2016076204 W CN 2016076204W WO 2016150309 A1 WO2016150309 A1 WO 2016150309A1
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composition
extract
skin
sylvestris
subject
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French (fr)
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韩强
张翌
李廷钊
杜军
李波
申晓娟
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Access Business Group International LLC
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Access Business Group International LLC
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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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9755—Gymnosperms [Coniferophyta]
    • A61K8/9767—Pinaceae [Pine family], e.g. pine or cedar
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention generally relates to a composition comprising Thalictrum for brightening the skin of a subject, and more particularly to a composition comprising Thalictrum petaloideum and using the composition to brighten the subject The method of the skin.
  • melanin Human skin coloration is determined by the amount and location of melanin on the skin surface.
  • Melanin is synthesized by oxidation of amino acid tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in cells present at the dermal-epidermal junction, commonly referred to as melanocytes.
  • L-DOPA L-3,4-dihydroxyphenylalanine
  • melanin is produced by melanocytes present at the dermal-epidermal junction, and the chemical nature of tyrosine in melanocytes is catalyzed by tyrosinase to form L-DOPA, followed by a series of enzymatic The reaction produces melanin.
  • This series of cellular processes is commonly referred to as melanogenesis.
  • the oxidation process is catalyzed by an enzyme called tyrosinase.
  • a series of cellular processes by melanocytes are commonly referred to as melanogenesis.
  • Skin coloration is regulated by the amount and type of melanin synthesized by melanocytes. Environmental factors can also affect skin color.
  • a healthy amount of melanin in the skin effectively absorbs ultraviolet ("UV") rays.
  • UV ultraviolet
  • a certain amount of melanin can effectively absorb ultraviolet radiation in the external environment.
  • Increased exposure of the skin to UV rays generally increases the amount and rate of melanin production (as the time and intensity of skin exposure to UV rays increases, the amount and rate of melanin production increases accordingly) and can lead to darker skin. (Darker skin tone), or "Sepia”.
  • Local or general pigmentation disorders such as hyperpigmentation or hypopigmentation, can be derived from a number of factors, including hormone levels in the body, diet, genetic disorders, and medications. Common pigmentation disorders include yellow brown Melisma, freckles and white spots.
  • compositions have been formulated to address pigmentation disorders and have been contemplated, for example, for treating hyperpigmentation and/or hypopigmentation. Such treatments are often referred to as "skin brightening,” “skin whitening,” or “skin whitening.”
  • skin lightening agents For example, brightening age spots (freckles or aging spots), diluting, or preventing blackening of Caucasian and Asian skins (ie, maintaining a bright/white complexion).
  • Some of these formulations have included tyrosinase inhibitors such as hydroquinone, vitamin C, kojic acid, arbutin, glutathione, cysteine, lactic acid, ferulic acid, nicotinamide, and plant extracts.
  • tyrosinase inhibitors such as hydroquinone, vitamin C, kojic acid, arbutin, glutathione, cysteine, lactic acid, ferulic acid, nicotinamide, and plant extracts.
  • a composition is disclosed.
  • the composition can be used topically to brighten (or whiten) the skin.
  • the composition comprises Pinus sylvestris.
  • the active ingredient of the composition consists of Pinus sylvestris.
  • the composition consists of Pinus sylvestris.
  • a cosmetic method of brightening the skin of a subject includes the step of applying the sylvestris chinensis to the skin of the subject.
  • the composition is typically applied in an amount and/or time sufficient to brighten the skin.
  • Figure 1 is a line graph illustrating cytotoxicity data ("Data 1");
  • Figure 2 is a line graph illustrating tyrosinase inhibition rate data ("data 2");
  • Figure 3 is a line graph illustrating melanin synthesis inhibition data ("data 3");
  • FIG. 4 is a line graph illustrating melanin elimination rate data ("data 4").
  • a composition is disclosed.
  • the composition is typically a topical composition.
  • the composition is used to brighten (or whiten) the skin. More specifically, the composition can be used to brighten the skin of a subject.
  • Subjects are usually human and can include men and women of all ages.
  • the composition is not limited to the location of the skin of a particular subject or subject. For example, a person can apply the composition to his face, neck, arms, hands, chest, torso, legs, feet, and the like, or any combination thereof. Such areas of the skin may be hyperpigmented or hypopigmented. Methods of using the compositions are further described below.
  • compositions of the present disclosure generally comprise an extract from a plant of the genus T. chinensis, more typically a plant from the species P. sylvestris.
  • T. chinensis can be used interchangeably with P. sylvestris, and vice versa.
  • embodiments of the present disclosure generally relate to topical compositions comprising an amount sufficient to reduce/inhibit melanin production in a subject in need thereof and/or to sufficiently eliminate the amount of melanin in a subject in need thereof.
  • An extract of a genus of grass such as an extract of the plant of the genus Pinus sylvestris.
  • the composition comprises T. chinensis, or T. chinensis.
  • the active ingredient of the composition consists of T. chinensis or consists of T. chinensis.
  • the composition may further consist of one or more additional components and/or inactive components.
  • the composition consists of T. chinensis or consists of T. chinensis.
  • the composition may comprise plant material from the genus Thalictopsis, including plant material from one or more species, such as the genus Thalictrum (also known as Thalictrum petaloideum L.).
  • T. chinensis is a genus of 120 to 200 perennial herbaceous flowering plants of the Ranunculaceae (buttercup), which is mainly found in temperate regions. Although its common name is "grass musk", T. chinensis is generally not related to real musk (Russaceae), but has a petiole of two or three points similar to its members.
  • Frederick musk is common in shady or humid places throughout the northern hemisphere and south to sub-worlds of southern Africa and tropical South America, but generally does not exist in Australasia. Tangsong grass is most common in the world temperature region, and at least 22 species exist in North America.
  • the leaves are alternately pinnately compound leaves, and the staining is usually aquamarine.
  • a typical natural product of the genus T. chinensis is the benzylisoquinoline alkaloid, such as xylanine and the structurally related alkaloid berberine.
  • T. chinensis examples include, but are not limited to, T. alpinum, T. aquilegiifolium, T. calabricum, T. cheridonii, T. clavatum, T. cooleyi, and T. delavayi, T.diffusiflorum, T. dibicum, T. dipterocarpum, T. fendleri, T. flavum , T. foeniculaceum, T. foetidum, T. foliolosum, T.
  • the grass can be selected from one or more of the foregoing.
  • the T. chinensis includes or is a P. sylvestris.
  • T. chinensis can be used in its original form, in suspended form, in dehydrated form, in concentrated form or in extract form. Typically, T. chinensis is in dry or liquid form. Extracts of this component and/or other components of the composition may be obtained by conventional extraction methods known in the art, such as extraction by water (e.g., steam) or by solvent (e.g., alcohol).
  • the compositions of the present disclosure are not limited to a particular extraction method. An exemplary extraction method is described below.
  • the composition comprises an extract from the species of Pinus sylvestris.
  • T. chinensis extract generally refers to extracts from the genus Thalictopsis, including from the individual (ie, "P. sylvestris extract") or with the genus One or more other combinations of the species of the genus Pinus sylvestris.
  • T. chinensis extracts are commercially available from a variety of sources.
  • an appropriate extract of T. chinensis can be obtained by using any conventional extraction technique.
  • extraction methods that can be used to produce extracts suitable for the composition. These methods include, but are not limited to, the extraction methods disclosed in U.S. Patent No. 7,897,184 to Rana, et al. While the extraction solvent described specifically refers to ethanol, it should be understood that other alcohols such as, but not limited to, isopropanol, ethyl alcohol, and/or methyl alcohol may be used in addition to or in place of ethanol.
  • Exemplary alcoholic solvents include, but are not limited to, a C 1 to C 4 alcohols such as methanol, ethanol, propanol, isopropanol and butanol; water - alcohol or mixture of alcohols and water, including water - ethanol (hydro-ethanol); Multi Hydroxy alcohols such as propylene glycol and butylene glycol; and fatty alcohols. Any of these alcohol solvents can be used. Other solvents such as, but not limited to, acetone can also be used as the extraction solvent. Any ratio of solvent-water admixtures such as alcohol-water and/or acetone-water admixtures can also be used.
  • the extract of T. chinensis can be obtained using an organic solvent extraction technique.
  • continuous extraction of the solvent can be used to obtain the extract of T. chinensis.
  • total water-ethanol extraction technique it is called a one-time extraction.
  • the extract produced in this process will contain a wide range of phytochemicals present in the extracted material, including fat soluble and water soluble phytochemicals. After collecting the extraction solution, the solvent was evaporated to obtain an extract.
  • Total ethanol extraction can also be used.
  • This technique uses ethanol as a solvent.
  • the extract produced by the extraction technique may include a fat-soluble and/or lipophilic compound in addition to the water-soluble compound.
  • Total methanol extraction can also be used in a similar manner with similar results.
  • the extract of T. chinensis is obtained by extracting plant material of the species of P. sylvestris by alcohol.
  • SFE supercritical fluid carbon dioxide supercritical extraction
  • CO 2 carbon dioxide
  • a supercritical state eg, >31.3 ° C and >73.8 bar
  • temperature and pressure conditions can be varied to achieve optimal extract yield.
  • This technique produces extracts of fat-soluble and/or lipophilic compounds similar to total hexane and ethyl acetate extraction techniques, which can also be used.
  • the extract of T. chinensis can be added to the composition in any amount.
  • the extract of T. chinensis is present in an amount effective to reduce (or inhibit) melanin production and/or eliminate melanin in the skin of the subject.
  • the extract of T. chinensis is present in an amount of from about 10 to about 300 [mu]g/mL of the composition.
  • the extract of T. chinensis is present in an amount of about 10, about 20, about 25, about 50, about 75, or about 100 [mu]g/mL of the composition.
  • Individual subranges and amounts of from about 10 to about 300 [mu]g/mL of composition, as well as amounts less than or greater than these amounts, are also contemplated.
  • the amount of T. chinensis extract present in the composition can depend on several factors, including the desired level of melanin inhibition, the level of melanin inhibition in the particular extract or composition, and other factors. In certain embodiments, based on 100 parts by weight ("pbw") composition, The extract of T. chinensis is present in an amount of from about 0.01 to about 20 pbw. In a further embodiment, the extract of T. chinensis is present in an amount of from about 0.05 to about 10 pbw based on the 100 pbw composition. Also contemplated are individual subranges and amounts of from about 0.01 to about 20 pbw, and amounts less than or greater than these amounts.
  • the composition further comprises a supplemental active ingredient.
  • the supplemental active ingredient is typically selected from the group consisting of Hovenia dulcis, Lycii Cortex or Lycium chinense, Galium aparine, and combinations thereof.
  • the supplemental active ingredient may be an extract from the northern carp, the sorghum species, and the original genus. Such extracts are commercially available or obtained by one of the above extraction techniques. Although optional, it is believed that any one or combination of these supplemental active ingredients can be used in combination with the extract of T. chinensis to further aid skin lightening. If used, the supplemental active ingredient can be employed in an amount as described for the extract of T. chinensis, for example, in an amount of from about 10 to about 300 [mu]g/mL of the composition or from about 0.01 to about 20 pbw of the composition.
  • the composition is free of other actives.
  • other active substances herein is meant generally that the composition does not contain other types of traditional Chinese medicines (“TCM”; or “Chinese medicine”) other than T. chinensis.
  • TCM traditional Chinese medicines
  • Other types of TCM are understood in the art. Examples of other types of TCMs are generally described as "biologically active substances" in International Publication No. WO 01/22934 A2, the contents of which are incorporated herein in entirety by reference.
  • the composition may comprise the following inactive materials. If used, inactive materials are different from other types of TCM.
  • compositions may be formulated to contain a cosmetically acceptable carrier (or vehicle) and prepared and/or packaged and labeled to increase skin lightening or whitening, inhibiting, reducing or reducing melanin production or pigmentation.
  • a cosmetically acceptable carrier or vehicle
  • the composition can be administered topically.
  • cosmetically acceptable carriers include, but are not limited to, water, glycerin, waxes, various alcohols such as ethanol, propanol, vegetable oils, minerals Oil, silicone such as silicone oil, fatty esters, fatty alcohols, glycols, polyglycols or any combination thereof. Such components are generally considered to be inactive components.
  • the final composition may be in any form suitable for topical application to the skin such as, but not limited to, aerosol sprays, gels, creams, dispersions, lotions, foams, liquids, lotions, mousses, patches, balms, Powder, pump spray, solid, solution, stick or towel.
  • the emulsions may include oil-in-water emulsions, water-in-oil emulsions, and water-in-silicone emulsions.
  • compositions of the present disclosure can be prepared using a variety of methods known in the art.
  • the method of preparation comprises the step of extracting plant material of the species of P. sylvestris to obtain an extract of P. sylvestris.
  • the method of preparation further comprises the step of combining one or more of the extract of P. sylvestris and a cosmetically acceptable carrier such as the above-described carrier.
  • the components can be combined using conventional production methods and devices such as mixers, blenders, and the like.
  • the composition can be used for skin lightening in a variety of ways.
  • a cosmetic method for brightening the skin of a subject includes the step of applying the P. sylvestris to the skin of the subject.
  • Pinus sylvestris can be applied in a variety of ways, including applying the composition to the skin of a subject.
  • the composition can be applied directly or indirectly to the skin, such as by hand, applicator, patch, and the like.
  • the composition can be applied as needed, daily, several times a day or any suitable protocol to achieve the desired result.
  • the frequency of local application can depend on several factors, including the level of melanin production inhibition desired.
  • the regimen includes applying the composition to the skin once or twice daily to include morning application and/or evening application.
  • the amount of the composition applied to the skin in each application may depend on several factors, including the level of the desired result and the particular composition.
  • Feed Extract Plant / vegetal weight 50 10 Flask volume (mL) 500 150 Methanol volume (mL) 300 60
  • a stir bar was added and the amount of methanol shown in the table was poured into the flask.
  • the flask opening was capped with aluminum foil.
  • the flask was placed on a magnetic stir plate and stirred using a slow/moderate agitation rate for at least 12 hours. Keep the sample away from direct light.
  • the flask was removed from the stir plate and sonicated for one hour at room temperature with occasional vortexing.
  • the sample solution was filtered through GF/A filter paper and directly into a 500 mL round bottom flask.
  • the solvent remaining in the round bottom flask was evaporated using a rotary evaporator. Reduce solvent volume to less than 10 mL.
  • the concentrated extract (still in liquid form) was transferred to a pre-weighed scintillation vial (without lid weighing) using a glass pipette. Further dilution with methanol for transfer purposes as needed.
  • the tube Place the tube under a nitrogen evaporator and use a slow stream of nitrogen to reduce the volume to the minimum possible.
  • the recommended bath temperature is 40 °C.
  • the tube was removed from the nitrogen evaporator and placed in a desiccator without drying until dry (about 12 hours). Record the final dry weight of the fraction in the scintillation tube (without cover) (calculated by difference). The tube is capped and stored in a freezer for further use.
  • Luminescent cell viability assay is a uniform method for determining the number of viable cells in culture based on the quantification of ATP present as an indicator of metabolically active cells. According to the cell-based safety evaluation of CTG as illustrated by Data 1 and Figure 1, there is no risk of cytotoxicity.
  • Arbutin is considered as a positive control for both inhibition of tyrosinase activity and inhibition of melanin synthesis, and hydroquinone is used as a positive control for the presence of melanin-eliminating activity.
  • the extract of Pinus sylvestris L. showed excellent tyrosinase inhibitory activity in B16F10 cells, with an inhibition rate of 93.2% at a concentration of 100 ⁇ g/mL relative to the same concentration of the positive control arbutin.
  • the tyrosinase inhibitory activity in B16F10 cells is comparable to or much better than that of arbutin. This data set is generally obtained by the assay methods listed below.
  • This program describes a standard method for inhibition of tyrosinase activity in B16 cells.
  • the assay plates were incubated for 24 hours at 37 ° C, 5% CO 2 under humidified conditions.
  • % inhibition (maximum signal - compound signal) / (maximum signal - minimum signal) x 100.
  • the inhibition rate of Pinus sylvestris was 107.0% at 100 ⁇ g/mL relative to the positive control arbutin.
  • the serotonin action in the B16F10 cells was comparable to that of arbutin in the B16F10 cells.
  • the sylvestris chinensis has the ability to strongly interrupt (block) or reduce the melanin synthesis process in B16F10 cells. This data set is generally obtained by the assay methods listed below.
  • This program describes a standard method for the inhibition of melanin synthesis in B16F10 cells.
  • the assay plates were incubated for 24 hours at 37 ° C, 5% CO 2 under humidified conditions.
  • % inhibition (maximum signal - compound signal) / (maximum signal - minimum signal) x 100.
  • This program describes a standard method for the determination of melanin in B16 cells.
  • the assay plates were incubated for 24 hours at 37 ° C, 5% CO 2 under humidified conditions.
  • the assay plates were incubated at 37 ° C, 5% CO 2 for 72 hours under humidified conditions.
  • % inhibition (maximum signal - compound signal) / (maximum signal - minimum signal) x 100.
  • the range of "0.1 to 0.9" can be further depicted as a smaller one-third, ie 0.1 to 0.3, the middle third, ie 0.4 to 0.6, and the larger one, ie 0.7 to 0.9, which is individual and generally within the scope of the appended claims, and may be relied upon and/or generally sufficient to provide sufficient embodiments within the scope of the appended claims. hold. Further, with respect to languages that define or modify a range, such as “at least”, “greater than”, “less than”, “not greater than”, etc., it is to be understood that such language includes sub-ranges and/or upper or lower limits.
  • a range of "at least 10" inherently includes a subrange of at least 10 to 35, a subrange of at least 10 to 25, a subrange of at least 25 to 35, and the like, and each subrange may be in an individual and/or population Sufficient support is provided for the specific embodiments within the scope of the appended claims.
  • individual values within the scope of the disclosure may be relied upon and provide sufficient support for the specific embodiments within the scope of the appended claims.
  • a range of "1 to 9" includes each individual integer, such as 3, and an individual value including a decimal point (or fraction), such as 4.1, which may be relied upon and provide sufficient support for a particular embodiment within the scope of the appended claims. .

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Abstract

一种皮肤增亮组合物，包含来自瓣蕊唐松草种的植物材料，例如提取物。所述组合物用于增亮皮肤的用途。

Description

包含唐松草的组合物及用于皮肤增亮的方法 发明领域
本发明大体涉及用于增亮受试者皮肤的包含唐松草(Thalictrum)的组合物，并且更具体涉及包含瓣蕊唐松草(Thalictrum petaloideum)的组合物以及使用所述组合物增亮受试者皮肤的方法。
相关技术描述
人类皮肤着色由皮肤表面黑色素的量和位置决定。黑色素通过存在于真皮-表皮交界处的、通常称为黑素细胞的细胞中氨基酸酪氨酸氧化至L-3，4-二羟基苯丙氨酸(L-DOPA)而合成。所述另一种方式，黑色素由存在于真皮-表皮交界处的黑色素细胞产生，化学本质为黑素细胞中的酪氨酸经酪氨酸酶催化氧化生成L-DOPA，之后经一系列酶促反应生成黑色素。这一系列细胞过程通常称为黑素生成。所述氧化过程由称为酪氨酸酶的酶催化。由黑素细胞进行的一系列细胞过程通常称为黑素生成。
皮肤着色通过黑素细胞合成的黑色素的量和类型来调控。环境因素也可影响皮肤颜色。皮肤中健康量的黑色素有效吸收紫外线(“UV”)射线。所述另一种方式，健康皮肤中，一定量的黑色素可有效吸收外界环境中的紫外线辐射。皮肤对UV射线增加的暴露一般增加黑色素生成的量和速率(随着皮肤暴露在UV射线下的时间和强度的增加，皮肤黑色素生成的量和速率也相应增加)，并且可以导致更黑的皮肤(肤色加深)，或者“棕褐色”。局部或总体的色素沉着疾患，例如色素沉着过度或色素沉着不足，可以源自许多因素，包括体内激素水平、饮食、遗传疾患和药物治疗。常见的色素沉着疾患包括黄褐 斑(melisma)、雀斑和白斑。
各种组合物已被配制以解决色素沉着疾患，并且例如已经预期用于治疗色素沉着过度和/或色素沉着不足。此类治疗通常被称为“皮肤增亮”、“皮肤美白”或“皮肤亮白”。存在皮肤美白剂的几种用途。例如，增亮老年斑(雀斑或衰老性色斑)，淡化，或者预防高加索人和亚洲人皮肤的黑化(即，维持亮/白肤色)。这些制剂中的一些已包括酪氨酸酶抑制剂例如氢醌、维生素C、曲酸、熊果苷、谷胱甘肽、半胱氨酸、乳酸、阿魏酸、烟酰胺，以及植物提取物例如熊果和桑树提取物等。然而，这些化合物的一些，例如氢醌和曲酸，具有副作用，包括皮肤刺激、急性皮炎和皮肤细胞的细胞毒性。
鉴于上文，依然存在提供其他皮肤增亮剂、特别是高效皮肤增亮剂的机会。最具体地，依然存在提供有效皮肤增亮剂并且将天然材料加入组合物以解决与常规化合物例如氢醌相关的问题的机会。
发明概述
公开了一种组合物。所述组合物可局部使用以增亮(或美白)皮肤。所述组合物包含瓣蕊唐松草。在某些实施方案中，所述组合物的活性成分由瓣蕊唐松草组成。在具体实施方案中，所述组合物由瓣蕊唐松草组成。
还公开了一种增亮受试者皮肤的美容方法。该方法包括应用瓣蕊唐松草至受试者皮肤的步骤。所述组合物一般以足以增亮皮肤的量和/或时间应用。
附图简述
本公开的其他优点将容易理解，因为通过参考以下详述并结合考虑附图而变得更好理解，附图中：
图1是示例说明细胞毒性数据(“数据1”)的线图；
图2是示例说明酪氨酸酶抑制率数据(“数据2”)的线图；
图3是示例说明黑色素合成抑制数据(“数据3”)的线图；和
图4是示例说明黑色素消除率数据(“数据4”)的线图。
发明详述
公开了一种组合物。所述组合物通常是局部组合物。所述组合物用于皮肤增亮(或美白)。更具体地，所述组合物可用于增亮受试者的皮肤。受试者通常是人，并且可以包括各年龄的男人和女人。所述组合物不限于特定受试者或受试者的皮肤位置。例如，一个人可以将所述组合物应用至其脸、颈、臂、手、胸、躯干、腿、脚等或其任意组合。此类皮肤区域可以是色素沉着过度或色素沉着不足的。使用所述组合物的方法在下文进一步描述。
令人惊讶地发现唐松草属(genus Thalictrum)可用于皮肤增亮。具体地，不受束缚或受限于任何特定理论，认为唐松草属的提取物减少和/或抑制黑色素生成。对于减少/抑制替代或附加地，认为唐松草属的提取物消除黑色素。本公开的组合物一般包含来自唐松草属的植物、更通常来自瓣蕊唐松草种的植物的提取物。如本文使用的，对唐松草的提及可与瓣蕊唐松草可互换地使用，并且反之亦然。基于本文发现，本公开的实施方案一般涉及局部组合物，其包含足以减少/抑制有相应需要的受试者黑色素生成的量和/或足以消除有相应需要的受试者中黑色素的量的唐松草属植物的提取物，例如瓣蕊唐松草种植物的提取物。
在各个实施方案中，所述组合物包含唐松草，或者瓣蕊唐松草。在进一步实施方案中，所述组合物的活性成分由唐松草组成，或者由瓣蕊唐松草组成。在这些实施方案中，所述组合物可以进一步由一种或多种附加组分和/或非活性组分组成。在某些实施方案中，所述组合物由唐松草组成，或者由瓣蕊唐松草组成。在所有这些实施方案中， 所述组合物可以包括来自唐松草属的植物材料，包括来自一个或多个种例如瓣蕊唐松草(还称为花唐松草(Thalictrum petaloideum L.))的植物材料。
唐松草是主要生在温带地区的毛莨科(Ranunculaceae)(毛茛属植物(buttercup))的120至200种多年生草本植物开花植物的属。尽管其常用名称是“草地芸香”，但唐松草种一般与真实芸香(芸香科)无关，但类似于其成员而具有二分或三分的叶柄。草地芸香常见于阴凉或潮湿的地方，遍布大部分北半球并且南至南部非洲和热带南美洲的子世界范围，但是一般不存在于澳大拉西亚。唐松草最常见于世界温度地区，至少22种存在于北美洲。叶子是交替回羽状复叶，染色通常为海蓝绿色。花小且无瓣(没有花瓣)，但是具有许多长雄蕊，通常是亮白色、黄色、粉色或浅紫色，并且以突出浓密花序生成。在一些种中，萼片是大的、亮色且花瓣状的，但是大多数情况下当花开时或不久之后它们是小且下垂的。唐松草属存在的典型天然产物是苄基异喹啉生物碱，例如木兰花碱和结构相关的生物碱小檗碱。
所述组合物的该组分的科学分类一般如下-目：毛莨目(Ranunculales)；科：毛莨科(Ranunculaceae)；和属：唐松草。唐松草(T.)的示例性种包括但不限于：高山唐松草(T.alpinum)、T.aquilegiifolium、T.calabricum、珠芽唐松草(T.chelidonii)、T.clavatum、T.cooleyi、偏翅唐松草(T.delavayi)、堇花唐松草(T.diffusiflorum)、异株唐松草(T.dioicum)、云南唐松草(T.dipterocarpum)、T.fendleri、黄唐松草(T.flavum)、丝叶唐松草(T.foeniculaceum)、腺毛唐松草(T.foetidum)、多叶唐松草(T.foliolosum)、T.glaucum、T.heliophilum、盾叶唐松草(T.ichangense)、爪哇唐松草(T.javanicum)、T.kiusianum、T.lucidum、T.macrostylum、亚欧唐松草(T.minus)、T.morrisonii、T.occidentale、T.orientale、美丽唐松草(T.reniforme)、瓣蕊唐松草(T.petaloideum)、T.polygamum、T.revolutum、T.rochebrunianum、箭头唐松草(T.simplex)、散花唐松草(T.sparsiflorum)、T.thalictroides、毛发唐松草(T.trichopus)、T.tuberosum和T.venulosum。唐松草的两 个或多个种之间的杂种也是可能的。在各个实施方案中，唐松草可以选自前述种的一个或多个。在许多实施方案中，唐松草包括或者是瓣蕊唐松草。
唐松草植物的任何部分可用于产生组合物中使用的材料，包括但不限于根、茎、根茎、叶、花、果实和/或这些部分的提取物。唐松草可以原始形式、悬浮形式、脱水形式、浓缩形式或提取物形式使用。通常，唐松草是干燥或液体形式。组合物的该组分和/或其他组分的提取物可以通过本领域已知的常规提取方法获得，例如通过水(例如蒸汽)提取或通过溶剂(例如醇)提取。本公开的组合物不限于特定的提取方法。示例性提取方法在下文描述。
在许多实施方案中，组合物包含来自瓣蕊唐松草种的提取物。如本文使用的，对“唐松草提取物”的提及一般指含有来自唐松草属的提取物，所述唐松草属包括来自单独(即“瓣蕊唐松草提取物”)或与唐松草属的一种或多种其他种组合的瓣蕊唐松草种。唐松草提取物可商业获自各种来源。此外，适当的唐松草提取物可以通过使用任何常规提取技术获得。
有许多可用于产生适合所述组合物的提取物的提取方法。这些方法包括但不限于Rana等人的美国专利号7,897,184中公开的提取方法，其在此通过引用整体并入本文，并且在下文参考一些提取方法而部分地复制。虽然描述的提取溶剂具体指乙醇，但是应该理解，其他醇，例如但不限于异丙醇、乙基醇和/或甲基醇可以补充或替代乙醇而使用。示例性醇溶剂包括但不限于C1至C4醇，例如甲醇、乙醇、丙醇、异丙醇和丁醇；水-醇或醇与水的混合物，包括水-乙醇(hydro-ethanol)；多羟基醇，例如丙二醇和丁二醇；和脂肪醇。可以使用这些醇溶剂的任何一个。其他溶剂，例如但不限于丙酮也可以作为提取溶剂使用。还可以使用任何比率的溶剂-水掺和物，例如醇-水和/或丙酮-水掺和物。
在一个实例中，可以使用有机溶剂提取技术获得唐松草提取物。在另一实例中，可以使用溶剂连续分级分离来获得唐松草提取物。还可以使用总的水-乙醇提取技术来获得唐松草提取物。一般而言，其称为一次性提取。在该过程中产生的提取物会含有宽范围的提取材料中存在的植物化学物，包括脂溶性和水溶性植物化学成分。在收集提取溶液之后，蒸发溶剂，得到提取物。
还可以使用总的乙醇提取。该技术使用乙醇作为溶剂。该提取技术产生的提取物除了水溶性化合物以外还可以包括脂溶性和/或亲脂化合物。也可以相似方式使用总甲醇提取，具有相似的结果。在各个实施方案中，通过醇提取瓣蕊唐松草种的植物材料而获得唐松草提取物。
可用于获得唐松草提取物的提取技术的另一实例是超临界流体二氧化碳超临界提取(“SFE”)。在该提取程序中，待提取的材料不暴露于任何有机溶剂。而是，提取溶剂是超临界状态(例如＞31.3℃和＞73.8巴)下的二氧化碳(CO2)，含有或没有调节剂。本领域技术人员会理解，温度和压力条件可以变化以获得最佳的提取物产率。该技术产生脂溶性和/或亲脂化合物的提取物，类似于总己烷和乙酸乙酯提取技术，其也可以使用。
唐松草提取物可以任何量加入组合物。通常，唐松草提取物以有效减少(或抑制)受试者皮肤黑色素生成和/或消除黑色素的量存在。在各个实施方案中，唐松草提取物以约10至约300μg/mL组合物的量存在。在具体实施方案中，唐松草提取物以约10、约20、约25、约50、约75或约100μg/mL组合物的量存在。还考虑约10至约300μg/mL组合物的各个子范围和量，以及小于或大于这些量的量。
组合物中存在的唐松草提取物的量可取决于几个因素，包括希望的黑色素抑制水平、特定提取物或组合物中的黑色素抑制水平、以及其他因素。在某些实施方案中，基于100重量份(“pbw”)组合物， 唐松草提取物以约0.01至约20pbw的量存在。在进一步实施方案中，基于100pbw组合物，唐松草提取物以约0.05至约10pbw的量存在。还考虑约0.01至约20pbw的各个子范围和量，以及小于或大于这些量的量。任选用于组合物的其他提取物或成分描述于Dornoff等人的美国专利号5,747,006，以及Leverett等人的美国专利号5,980,904、6,994,874、7,060,304、7,247,321和7,364,759，其公开内容通过引用整体并入本文。
在某些实施方案中，除了瓣蕊唐松草，组合物还包含补充活性成分。补充活性成分通常选自以下组：北枳椇(Hovenia dulcis)、地骨皮或枸杞(Lycii Cortex or Lycium chinense)、原拉拉藤(Galium aparine)及其组合。在这些实施方案中，补充活性成分可以是来自北枳椇种、枸杞种和原拉拉藤种的提取物。此类提取物可以商业途径获得，或者通过上述提取技术之一获得。虽然是任选的，但是认为这些补充活性成分的任何一个或组合可与唐松草提取物组合使用以进一步帮助皮肤增亮。如果使用，补充活性成分可以如针对唐松草提取所述的量使用，例如以约10至约300μg/mL组合物或者约0.01至约20pbw组合物的量。
在某些实施方案中，组合物不含其他活性物质。这里的“其他活性物质”一般表示组合物不含不同于唐松草的其他类型的传统中药(“TCM”；或“中药”)。其他类型的TCM是本领域所理解的。其他类型的TCM的实例一般在国际公开号WO 01/22934 A2中描述为“生物活性物质”，其内容通过引用整体并入本文。在某些实施方案中，组合物可以包含下述无活性物质。如果使用，无活性物质不同于其他类型的TCM。
可以配制组合物以包含美容上可接受的载体(或媒介物)并制备和/或包装并标示为增加皮肤增亮或美白，抑制、降低或减少黑色素生成或色素沉着。组合物可以局部施用。美容上可接受的载体的实例包括但不限于水、甘油、蜡、各种醇例如乙醇、丙醇、植物油、矿物 油、硅酮例如硅油、脂肪酯、脂肪醇、二醇、聚二醇或其任意组合。此类组分一般被认为是非活性组分。最终组合物可以是适合局部应用于皮肤的任何形式，例如但不限于气溶胶喷雾剂、凝胶、乳霜、分散液、乳液、泡沫、液体、洗液、摩丝、贴片、香膏剂、粉剂、泵式喷雾剂、固体、溶液、粘棒或小巾。乳液可以包括水包油乳液、油包水乳液和硅酮包水乳液。
可以使用本领域已知的各种方法制备本公开的组合物。在制备组合物的一个实例中，制备方法包括提取瓣蕊唐松草种的植物材料以获得瓣蕊唐松草提取物的步骤。制备方法还包括组合瓣蕊唐松草提取物与美容上可接受的载体例如上述载体的一种或多种的步骤。可以使用常规生产方法和装置例如混合器、掺和器等来组合组分。
组合物可以各种方式用于皮肤增亮。作为例子，用于增亮受试者皮肤的美容方法包括将瓣蕊唐松草应用于受试者皮肤的步骤。瓣蕊唐松草可以各种方式应用，包括将组合物应用于受试者皮肤。可以将组合物直接或间接应用于皮肤，例如通过手、涂布器、贴片等。
可以按需要、每天、一天几次或者任何适当方案施用组合物，以便实现所需结果。在美容方法中，局部应用频率可以取决于几个因素，包括所需的黑色素生成抑制水平。一般而言，方案包括每天一次或两次应用组合物于皮肤以包括早上应用和/或晚上应用。每次应用中应用于皮肤的组合物的量可以取决于几个因素，包括希望结果的水平和具体组合物。
示例说明本公开组合物和方法的以下实施例预期示例说明而非限制本发明。
实施例
下文描述了示例性的提取方法。该提取方法用于获得本公开组合物的瓣蕊唐松草提取物。该提取方法可以称为甲醇分级分离或甲醇提 取。本领域技术人员会理解，其他提取方法也可以用于获得想要的提取物，包括上述那些。与确定皮肤增亮效力相关的其他提取方法和分析方法(例如测定方法)描述于Rana等人的国际公布号WO 2011/019468 A2、WO 2011/109139 A2和WO 2013/169634 A2，其公开内容通过引用并入本文。
示例性提取方法
使用的任何材料或提取物应该是粉末形式。根据下表称取并记录(至最接近的0.1g)样品进入烧瓶：
  进料 提取物
植物/植物性药材重量(g) 50 10
烧瓶体积(mL) 500 150
甲醇体积(mL) 300 60
添加搅拌棒并将表中所示量的甲醇倒入烧瓶。使用铝箔封盖烧瓶开口。将烧瓶放在磁力搅拌板上并使用缓慢/中等搅拌速率搅拌至少12小时。保持样品避免直射光。从搅拌板取出烧瓶并在室温下超声处理一小时，偶尔涡旋。
通过GF/A滤纸过滤样品溶液，直接进入500mL圆底长颈烧瓶。使用旋转蒸发仪蒸发圆底长颈烧瓶中剩余的溶剂。减少溶剂体积至小于10mL。使用玻璃移液管将浓缩提取物(依然是液体形式)转移至预先称重的闪烁管(无盖称重)。根据需要为转移目的使用甲醇进一步稀释。
将管置于氮蒸发仪下并使用缓慢氮流减少体积至最小可能。推荐的水浴温度是40℃。从氮蒸发器取出管并将其无盖放入干燥器直至干燥(大约12小时)。记录闪烁管中级分的最终干重(无盖)(通过差异计算)。给管加帽并储存于冷藏器供进一步使用。
使用前述提取方法获得瓣蕊唐松草提取物之后，进行各种测试并 产生相应的数据集以确定瓣蕊唐松草提取物在皮肤增亮方面的效力。在相关部分，使用本领域技术人员已知的效力测定和方法评价细胞毒性、酪氨酸酶抑制、黑色素合成抑制和黑色素消除。表格化数据提供于以下的数据1、数据2、数据3和数据4集以及各自相应的图1、2、3和4。
数据1
瓣蕊唐松草在B16F10中的细胞毒性-CTG(氢醌作为参比)
Figure PCTCN2016076204-appb-000001
Promega Corporation的
Figure PCTCN2016076204-appb-000002
(CTG)发光细胞活力测定是测定培养物中存活细胞数目的均一方法，基于作为代谢活性细胞指示而存在的ATP的定量。根据通过数据1和图1中示例说明的CTG的基于细胞的安全性评价，瓣蕊唐松草没有细胞毒性风险。
根据体外生物测定数据，发现瓣蕊唐松草的药草提取物具有皮肤增亮和去色素沉着的效力。通过模型细胞B16F10施用基于细胞的测定，监测酪氨酸酶活性抑制、黑色素合成抑制和存在的黑色素消除活性。该类型的基于模型细胞B16F10细胞的测定是本领域技术人员已知的。
熊果苷被视为酪氨酸酶活性抑制和黑色素合成抑制两者的阳性对照，而氢醌用作存在的黑色素消除活性的阳性对照。总结以下描述的结果，瓣蕊唐松草作为皮肤增亮或去色素沉着试剂在体外测试中具有突出活性而没有细胞毒性风险。
数据2
瓣蕊唐松草在B16F10中的酪氨酸酶抑制率(熊果苷作为参比)
瓣蕊唐松草
Figure PCTCN2016076204-appb-000003
熊果苷
Figure PCTCN2016076204-appb-000004
瓣蕊唐松草提取物在B16F10细胞中发挥优良的酪氨酸酶抑制活性，相对于相同浓度的阳性对照熊果苷，在100μg/mL浓度下具有93.2％的抑制率。具体地，如在数据2和图2中示例说明的，瓣蕊唐松草在B16F10细胞中酪氨酸酶抑制活性方面与熊果苷作用相当或好得多。该数据集一般通过下文即将列出的测定方法而获得。
酪氨酸酶抑制测定方法：
目的：该程序描述了B16细胞中酪氨酸酶活性抑制测定的标准方法。
细胞系：B16-F10(ATCC#)
材料：
·用于B16的RPMI 1640(GIBCO#22400-089批号1006397)
·胎牛血清(GIBCO#10099-141)
·胰蛋白酶-EDTA(GIBCO#25200-072)
·24孔板(Costar)
·96孔板(Costar)
·L-Dopa
程序：
第1天：铺板细胞
1.胰蛋白酶化盘并测定细胞密度。
2.以18,000细胞/ml的密度稀释细胞浆至所需体积。
3.将1ml/孔细胞浆分配至24孔测定板上。
4.在加湿条件下以37℃、5％CO2孵育测定板24小时。
第2天：添加测试化合物
1.根据板图制备参比和测试化合物溶液(200×)。
2.将5μl化合物转移至测定板(最终浓度：1×)。
3.在加湿条件下以37℃、5％CO2孵育板72小时。
第5天：使板成像
1.在培养基废物接收器上振摇倒置的板并用清洁纸巾吸干。
2.添加80μl 0.05mM PBS(0.1％Triton-X)，-80℃冷冻4小时。
3.室温融化板。重复步骤2&3两次。
4.将样品转移进入96孔V底板，3000RPM旋降10分钟。
5.将60μl上清液样品转移至UV板。每个孔中添加140μl新鲜0.1％L-DOPA并在37℃孵育1小时。
6.读取475nm下吸光度。
7.将5μl上清液样品转移至另一UV板以用BCA测定蛋白浓度。
数据处理：
·使用GraphPad。
·％抑制＝(最大信号-化合物信号)/(最大信号-最小信号)×100。
·基础信号获自没有L-DOPA的细胞。
·最大信号获自L-DOPA的作用。
数据3
瓣蕊唐松草在B16F10中的黑色素合成抑制(熊果苷作为参比)
瓣蕊唐松草
Figure PCTCN2016076204-appb-000005
熊果苷
Figure PCTCN2016076204-appb-000006
在B16F10细胞中黑色素合成抑制活性中，相对于阳性对照熊果苷，瓣蕊唐松草的抑制率在100μg/mL下是107.0％。具体地，如数据3和图3示例说明的，瓣蕊唐松草在B16F10细胞中黑色素合成抑制活性方面与熊果苷作用相当。这意味着瓣蕊唐松草有能力强烈中断(阻断)或减少B16F10细胞中黑色素合成过程。该数据集一般通过下文即将列出的测定方法而获得。
黑色素合成抑制测定：
目的：该程序描述了B16F10细胞中黑色素合成抑制测定的标准方法。
细胞系：B16-F10(ATCC#)
材料：
·用于B16的RPMI 1640(GIBCO#22400-089批号1006397)
·胎牛血清(GIBCO#10099-141)
·胰蛋白酶-EDTA(GIBCO#25200-072)
·1M NaOH
·24孔板(Corning)
程序：
第1天：铺板细胞
1.胰蛋白酶化盘并测定细胞密度。
2.以18,000细胞/ml的密度稀释细胞浆至所需体积。
3.将1ml/孔细胞浆分配至测定板上。
4.在加湿条件下以37℃、5％CO2孵育测定板24小时。
第2天：添加测试化合物
1.根据板图制备参比和测试化合物溶液(200×)。
2.将5μl化合物转移至测定板(最终浓度：1×)。
3.在加湿条件下以37℃、5％CO2孵育板72小时。
第5天：使板成像
1.去除培养基。
2将150μl1M NaOH添加至测定板。
3.在80℃下孵育板30分钟。
4.将140μl溶液转移至UV板。测试400nm信号。
5.将5μl溶液转移至UV板。向每个孔添加200μl BCA试剂并在37℃孵育20分钟。测试562nm信号。
数据处理：
·使用GraphPad。
·％抑制＝(最大信号-化合物信号)/(最大信号-最小信号)×100。
·最大信号获自DMSO的作用。
·最小信号获自200μg/ml熊果苷。
数据4
瓣蕊唐松草在B16F10中的黑色素消除率(氢醌作为参比)
瓣蕊唐松草
Figure PCTCN2016076204-appb-000007
氢醌
Figure PCTCN2016076204-appb-000008
在存在的黑色素消除测定中，相对于阳性对照氢醌在100μg/mL时76.0％的消除率，发现B16F10培养细胞中14.0％色素在添加100μg/mL瓣蕊唐松草72小时之后消除。这意味着瓣蕊唐松草也用于黑色素消除。该数据集一般通过以下即将列出的测定方法而获得。
存在的黑色素消除测定：
目的：该程序描述了B16细胞中黑色素消除测定的标准方法。
细胞系：B16-F10(ATCC#)
材料：
·用于B16的RPMI 1640(GIBCO#22400-089批号1006397)
·胎牛血清(GIBCO#10099-141)
·胰蛋白酶-EDTA(GIBCO#25200-072)
·1M NaOH
·24孔板(Corning)
程序：
第1天：铺板细胞
1.胰蛋白酶化盘并测定细胞密度。
2.以18,000细胞/ml的密度稀释细胞浆至所需体积。
3.将1ml/孔细胞浆分配至测定板上。
4.在加湿条件下以37℃、5％CO2孵育测定板24小时。
第2天：细胞处理
1.每孔添加10μM毛喉素和50μM 8-MOP。
2.在加湿条件下以37℃、5％CO2孵育测定板72小时。
第5天：添加测试化合物
1.更换新鲜培养基，每孔1ml。
2.根据板图制备参比和测试化合物溶液(200×)。
3.将5μl化合物转移至测定板(最终浓度：1×)。
4.在加湿条件下以37℃、5％CO2孵育板72小时。
第8天：使板成像
1.去除培养基。
2.将150μl1M NaOH添加至测定板。
3.在80℃下孵育板30分钟。
4.将140μl溶液转移至UV板。测试400nm信号。
5.将5μl溶液转移至UV板。向每个孔添加200μl BCA试剂并在37℃孵育20分钟。测试562nm信号。
数据处理：
·使用GraphPad。
·％抑制＝(最大信号-化合物信号)/(最大信号-最小信号)×100。
·最大信号获自没有化合物作用细胞。
·最小信号获自10μM毛喉素和50μM 8-MOP。
要理解，所附权利要求不限于详述中描述的明确和特定的化合物、组合物或方法，其可以在落入所附权利要求范围内的特定实施方案之间变化。对于本文用于描述各个实施方案特定特征或方面所依据的任何马库什组而言，要理解，不同的、特殊的和/或未预料的结果可以获自各个马库什组的每个成员而独立于所有其他马库什成员。马库什组的每个成员可以被单独或组合地依据并提供对所附权利要求范围内具体实施方案的足够支持。
还要理解，描述本发明各个实施方案中所依据的任何范围和子范围独立且总体落入所附权利要求范围，并且被理解为描述和涵盖包括其中全部和/或部分值在内的所有范围，即使此类值没有在本文明确书写。本领域技术人员容易发现，列举的范围和子范围充分描述并实现了本发明的各个实施方案，并且此类范围和子范围可以进一步描绘成相关的二分之一、三分之一、四分之一、五分之一等。仅作为一个实例，“0.1至0.9”的范围可以进一步描绘成较小的三分之一，即0.1至0.3，中间三分之一，即0.4至0.6，和较大的三分之一，即0.7至0.9，其个体且总体上在所附权利要求范围内，并且可以在个体和/或总体上被依据并提供对所附权利要求范围内具体实施方案的足够支 持。此外，关于限定或修饰范围的语言，例如“至少”、“大于”、“小于”、“不大于”等，要理解此类语言包括子范围和/或上限或下限。作为另一实例，“至少10”的范围固有包括至少10至35的子范围，至少10至25的子范围，至少25至35的子范围等等，并且每个子范围可以在个体和/或总体上被依据并提供对所附权利要求范围内具体实施方案的足够支持。最后，所公开范围内个体数值可以被依据并提供对所附权利要求范围内具体实施方案的足够支持。例如，“1至9”的范围包括各个个体整数，例如3，以及包括小数点(或分数)的个体数值，例如4.1，其可以被依据并提供对所附权利要求范围内具体实施方案的足够支持。
本文已经以示例说明的方式描述了本发明，并且要理解，已经使用的术语预期在描述词语性质内而不是限制。鉴于以上教导，本发明的许多调整和变化是可能的。本发明可以在所附权利要求范围内以不同于具体描述的方式实施。在本文明确考虑独立权利要求和从属权利要求(单项和多项从属)的所有组合的主题。

Claims (20)

  1. 一种用于皮肤增亮的组合物，所述组合物包含瓣蕊唐松草。
  2. 一种用于皮肤增亮的局部组合物，所述组合物的活性成分由瓣蕊唐松草组成。
  3. 如权利要求1或2所述的组合物，其中所述组合物包含来自瓣蕊唐松草种的提取物。
  4. 如权利要求3所述的组合物，其中所述瓣蕊唐松草提取物以有效减少受试者中黑色素生成和/或消除黑色素的量存在。
  5. 如权利要求3所述的组合物，其中所述瓣蕊唐松草提取物以约10至约300μg/mL所述组合物的量存在。
  6. 如权利要求3所述的组合物，其中所述瓣蕊唐松草提取物通过醇提取所述瓣蕊唐松草种的植物材料而获得。
  7. 如权利要求1或2所述的组合物，还包含美容上可接受的载体。
  8. 如权利要求7所述的组合物，其中所述美容上可接受的载体选自由以下组成的组：水、甘油、蜡、醇、植物油、矿物油、硅酮、脂肪酯、脂肪醇、二醇、聚二醇及其组合。
  9. 如权利要求1所述的组合物，还包含选自由以下组成的组的补充活性成分：枳椇子、地骨皮、原拉拉藤及其组合。
  10. 如权利要求9所述的组合物，其中所述补充活性成分包含来自枳椇子种、地骨皮和原拉拉藤的提取物。
  11. 如权利要求10所述的组合物，其中所述补充活性成分提取物以约10至约300μg/mL所述组合物的量存在。
  12. 如权利要求9至11任一项所述的组合物，还包含美容上可接受的载体。
  13. 如权利要求12所述的组合物，其中所述美容上可接受的载体选自由以下组成的组：水、甘油、蜡、醇、植物油、矿物油、硅酮、脂肪酯、脂肪醇、二醇、聚二醇及其组合。
  14. 一种用于皮肤增亮的局部组合物，所述组合物由瓣蕊唐松草组成。
  15. 权利要求1、2或14任一项所述的组合物用于增亮受试者皮肤的用途。
  16. 一种制备权利要求1、2或14任一项所述的组合物的方法，所述方法包括提取所述瓣蕊唐松草种的植物材料以获得瓣蕊唐松草提取物的步骤。
  17. 如权利要求16所述的方法，还包括组合所述瓣蕊唐松草提取物与美容上可接受的载体的步骤。
  18. 一种用于增亮受试者皮肤的美容方法，所述方法包括应用瓣蕊唐松草至受试者皮肤的步骤。
  19. 如权利要求18所述的方法，其中所述应用步骤进一步限定为应用组合物至受试者皮肤，其中所述组合物包含来自所述瓣蕊唐松草种的提取物。
  20. 如权利要求19所述的方法，其中所述瓣蕊唐松草提取物以有效减少受试者皮肤中黑色素生成和/或消除黑色素的量存在。
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