WO2013075333A1 - 新橙皮苷的新用途 - Google Patents

新橙皮苷的新用途 Download PDF

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Publication number
WO2013075333A1
WO2013075333A1 PCT/CN2011/082950 CN2011082950W WO2013075333A1 WO 2013075333 A1 WO2013075333 A1 WO 2013075333A1 CN 2011082950 W CN2011082950 W CN 2011082950W WO 2013075333 A1 WO2013075333 A1 WO 2013075333A1
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WIPO (PCT)
Prior art keywords
neohesperidin
skin
microcirculation
weight
condition
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Application number
PCT/CN2011/082950
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English (en)
French (fr)
Inventor
胡柳
蓝红英
Original Assignee
浙江养生堂天然药物研究所有限公司
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Application filed by 浙江养生堂天然药物研究所有限公司 filed Critical 浙江养生堂天然药物研究所有限公司
Priority to US14/359,971 priority Critical patent/US10335356B2/en
Priority to JP2014542664A priority patent/JP6175067B2/ja
Priority to PCT/CN2011/082950 priority patent/WO2013075333A1/zh
Priority to KR1020147015756A priority patent/KR101817187B1/ko
Priority to EP11876379.6A priority patent/EP2783690B1/en
Publication of WO2013075333A1 publication Critical patent/WO2013075333A1/zh
Priority to US16/407,482 priority patent/US11260011B2/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • A61K8/602Glycosides, e.g. rutin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/75Rutaceae (Rue family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/005Preparations for sensitive skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics 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
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]

Definitions

  • the present invention relates to a novel use of new hesperidin, in particular for cosmetic use, and more particularly to the action of neohesperidin as a chemical component for improving skin microcirculation, particularly for the removal of dark eyelids in the eye.
  • New use Background technique
  • the structure of the skin of the human eye is different from other parts of the human skin.
  • the skin around the eye is very thin only 1/10 of the skin thickness of other parts. After the light is refracted, it is easy to appear purple black in the eye, forming a black eyelid. Fatigue, stress, and lack of sleep are important factors leading to microcirculatory disorders.
  • the eye products that are sold on the market to improve skin microcirculation are endless, and most of them are added with some plants. Extracts, but on the one hand, what kind of ingredients or ingredients in these extracts are not clear, on the other hand, the effect of removing these black eyelids from these products is not obvious, and most of them improve skin microcirculation (for example, for blackening)
  • the products of the eyelids have not produced the desired effects (such as the effect of dark eyes) after being used by consumers.
  • Neohesperidin is a dihydroflavonoid derived from the genus Rutaceae (Latin name:
  • the present inventors have surprisingly found that the use of neohesperidin or plant extracts containing neohesperidin may have Effectively improve skin microcirculation, especially to improve eye microcirculation, and more particularly to effectively remove dark eyelids.
  • the present invention has been completed based on the above findings.
  • the first aspect of the present invention provides a novel hesperidin or a plant extract comprising neohesperidin for the preparation of a microcirculation for improving and/or promoting, or for eliminating and/or alleviating skin microcirculation.
  • a novel hesperidin or a plant extract comprising neohesperidin for the preparation of a microcirculation for improving and/or promoting, or for eliminating and/or alleviating skin microcirculation.
  • Use in products of illness or condition Use, for example, in products for improving and/or promoting microcirculation of the skin of a mammal, particularly a human, or for eliminating and/or alleviating a condition or condition associated with poor microcirculation of the skin of a mammal, particularly a human. .
  • the skin microcirculation is an ocular skin microcirculation.
  • condition or condition associated with poor skin microcirculation refers to a condition or condition associated with poor microcirculation of the ocular surface of the eye.
  • condition or state associated with poor microcirculation of the ocular surface of the eye refers to black eyelids.
  • the plant extract comprising neohesperidin refers to an extract obtained by extracting the fruit of the genus Poncirus trifoliata (L.) Raf.
  • the plant extract containing neohesperidin refers to an extract obtained from fruit extraction of Poncirus trifoliata (L.) Raf.
  • the content of neohesperidin in the extract is not less than 50% by weight.
  • the content of neohesperidin in the extract is 60% by weight or more, 70% by weight or more, 80% by weight or more, 85% by weight or more, 90% by weight or more, or 95% by weight or more.
  • the product is a product for topical application to the ocular skin.
  • the product is in the form of a solution, a milk, a paste, a cream, or a gel.
  • the product comprises: (1) neohesperidin or a plant extract comprising neohesperidin, and (2) a physiologically acceptable excipient.
  • the product comprises: (1) neohesperidin or a plant extract comprising neohesperidin, and (2) a physiologically acceptable excipient;
  • the percentage of total hesperidin or plant extract containing neohesperidin to the total weight of the product is 0.01-20% by weight based on neohesperidin. In one embodiment.
  • the percentage of the total hesperidin or the plant extract containing the new hesperidin to the total weight of the product is 0.01 to 15 parts by weight based on the neohesperidin. / 0 , 0.01-10 weight. / 0 , 0.05-15% by weight, 0.1-10% by weight, 0.2-10% by weight, or 0.2-5% by weight.
  • a second aspect of the invention provides a composition comprising: (1) an effective amount of neohesperidin or a plant extract comprising neohesperidin, and optionally (2) a physiologically acceptable excipient.
  • a composition according to the second aspect of the invention comprising: (1) an effective amount of neohesperidin or a plant extract comprising neohesperidin, and optionally (2) a physiologically acceptable excipient; Wherein the neohesperidin or plant extract comprising neohesperidin comprises from 0.01 to 20% by weight, based on the total weight of the composition, of neohesperidin. In one embodiment. The percentage of the total hesperidin or the plant extract containing the new hesperidin to the total weight of the composition is 0.01 to 15% by weight, 0.01 to 10% by weight based on the neohesperidin. / 0 , 0.05-15% by weight, 0.1-10% by weight, 0.2-10% by weight, or 0.2-5% by weight.
  • composition according to the second aspect of the present invention wherein the plant extract containing neohesperidin refers to a fruit of the genus Poncirus trifoliata (L.) Raf. Extract the obtained extract.
  • composition according to the second aspect of the present invention wherein the plant extract containing neohesperidin refers to an extract obtained from fruit extraction of Poncirus trifoliata (L.) Raf.
  • the content of neohesperidin in the extract is not less than 50% by weight.
  • the content of neohesperidin in the extract is 60% by weight or more, 70% by weight or more, 80% by weight or more, 85% by weight or more, 90% by weight or more, or 95% by weight or more.
  • the skin microcirculation is an ocular skin microcirculation.
  • the condition or condition associated with poor skin microcirculation refers to a condition or condition associated with poor microcirculation of the ocular surface of the eye.
  • the condition or condition associated with poor microcirculation of the ocular surface of the eye refers to dark eyelids.
  • composition according to the second aspect of the invention which is a product for topical application.
  • the composition according to the second aspect of the present invention which is a product for topical application for external application to the skin.
  • composition according to the second aspect of the invention which is a product for topical application to the skin of the eye.
  • composition according to the second aspect of the invention which is a cosmetic.
  • a composition according to the second aspect of the invention which is in the form of a solution, a milk, a paste, a cream, or a coagulum.
  • a third aspect of the invention provides a method of ameliorating and/or promoting skin microcirculation in an individual in need thereof, or eliminating and/or alleviating a condition or condition associated with poor microcirculation of the skin, the method comprising administering to the individual an effective amount of New hesperidin or a plant extract containing neohesperidin.
  • a method according to the third aspect of the invention wherein said skin microcirculation is an ocular skin microcirculation.
  • the method according to the third aspect of the present invention, wherein the condition or state associated with poor skin microcirculation refers to a condition or state associated with poor microcirculation of the ocular surface of the eye.
  • condition or state associated with poor microcirculation of the ocular skin refers to black eyelids.
  • the plant extract containing neohesperidin refers to an extract obtained by extracting the fruit of Poncirus trifoliata (L.) Raf.
  • the plant extract containing neohesperidin refers to an extract obtained from fruit extraction of Poncirus trifoliata (L.) Raf.
  • the content of neohesperidin in the extract is not less than 50% by weight.
  • the content of neohesperidin in the extract is 60% by weight or more, 70% by weight or more, 80% by weight or more, 85% by weight or more, 90% by weight or more, or 95% by weight or more.
  • neohesperidin or the plant extract containing neohesperidin is administered in the form of a solution, a milk, a paste, a cream, or a gel.
  • skin microcirculation refers to the microvascular network under the dermis of the skin, which is the terminal part of the circulation, which belongs to the capillaries, is the junction of arteries and veins, and is the place where the blood and tissue cells exchange material. .
  • Skin microcirculation is a complex dynamic system that plays an important role in skin color, temperature regulation, skin metabolism and transdermal transport, directly affecting skin health.
  • disease or condition associated with poor microcirculation of the skin refers to a pathological or non-pathological physical condition or abnormality that occurs due to poor microcirculation or disorder of the skin, such as dermatitis, pigmentation. Calming, skin aging, pale skin, red blood, local skin bloated, local hoarding, black eyelids, etc.
  • “Illness or condition” means that a pathological or non-pathological state of the body or an abnormal condition occurs due to poor microcirculation or disorder of the skin, such as improving local microcirculation of the skin, promoting local microcirculation of the skin, and eliminating skin due to A pathological or non-pathological physical state or abnormal condition occurs due to local microcirculation failure or disorder, and a pathological or non-pathological physical state or abnormal condition due to local microcirculation or disorder of the skin is alleviated.
  • physiologically acceptable means physiologically compatible, especially when used in contact with the skin for use in external skin products, for example, without causing side effects such as irritation to the skin.
  • a diluent for example, a surfactant, a thickener, an emollient, or the like which can be used in cosmetics.
  • the term "effective amount” refers to a dose that can achieve treatment, prevention, alleviation, and/or alleviation of a disease or condition described herein in a subject.
  • composition may also mean “cosmetic”, “cosmetic composition”, “pharmaceutical composition”, which may be used to achieve treatment, prevention, alleviation and/or alleviation in an individual.
  • the invention is a disease, disorder, or physical condition.
  • the term "individual” may also mean “subject", "patient” or other skin microcirculation that receives the composition of the invention to ameliorate and/or promote its appearance, or eliminate and/or An animal, particularly a mammal, such as a human, a dog, a monkey, a cow, a horse, etc., especially a human, which alleviates the condition or condition associated with poor microcirculation of the skin.
  • ocular skin microcirculation refers to microcirculation in the skin surrounding the eye.
  • the novel hesperidin can be obtained by extracting the fruit of the genus Poncirus trifoliata (L.) Raf., or can be synthesized according to chemical methods known in the art or biotransformed.
  • the neohesperidin may be a monomeric compound or an extract having a neohesperidin content of not less than 50% (w/w).
  • neohesperidin is 0.01%-20% (w/w), preferably 0.05%-15% (w/w), most preferably 0.1%, based on the amount of neohesperidin monomer compound used. A concentration of 10% (w/w) is used in the composition of the present invention.
  • the present invention also encompasses cosmetic skin care compositions containing neohesperidin.
  • the present invention relates to a cosmetic skin care composition
  • a cosmetic skin care composition comprising: (1) neohesperidin present in an amount of from 0.1% to 10% by weight; and (2) an acceptable medium in cosmetics Things.
  • neohesperidin in the compositions of the present invention is intended to achieve the effect of eliminating eye black eyes.
  • compositions and methods of the present invention also include a cosmetically acceptable vehicle as a diluent, dispersant or carrier for the active ingredient in the compositions to facilitate the distribution of the composition when it is applied to the skin.
  • External vehicles include liquid or solid emollients, surfactants, solvents,
  • an active substance is defined as a substance that is different from an emollient and an ingredient that only improves the physical properties of the composition.
  • composition having the following formulation:
  • Methyl glucose sesquistearate 0.5-5 wt%
  • the effect of reducing or eliminating dark eyelids in the eye can be achieved by topical application of neohesperidin.
  • the present invention relates to a novel use of neohesperidin in cosmetics, in particular, new hesperidin as a new chemical application for improving skin microcirculation in eliminating eye black eyelids.
  • the neohesperidin is present in an amount of from 0.01% to 10% by weight of the composition.
  • the present invention has studied the effect of the local application of neohesperidin on the surface of the skin, and the results show that the topical application of the new hesperidin can significantly improve the skin microcirculation. Applying it to eye care products, it was found that neohesperidin has a significant effect of eliminating dark eyelids.
  • % means wt%, i.e., weight percent, unless otherwise specified.
  • Microcirculation test method Take a male Japanese white rabbit with a body weight of 3.0-3.5k g . After shaving the back, mark 10 points of blood flow in the hairless area of the rabbit with a marker, 5 points on the left and right sides. , draw points to avoid large blood vessels; use laser Doppler flowmeter before applying samples The blood flow basal values of the experimental rabbits at 10 points were determined. Each group of rabbits was coated with a blank solution on the left side and a solution containing neohesperidin on the right side (three groups of animals, the concentration of the liquid was
  • Example 2 Effect of new hesperidin on the removal of dark eyelids in the eye
  • METHODS This study used an eight-week two-use contrast test on both sides of the eye.
  • 50 moderate-to-severe black-eyed volunteers were recruited to ensure that the effective number of each paired comparison group was 15.
  • the subjects were randomly assigned and left/right balanced, with a composition containing neohesperidin on one side and a composition containing no new hesperidin on the other side for 8 weeks.
  • the efficacy of the black eyelid removal effect was evaluated at 0 weeks (before treatment), 2 weeks, 4 weeks, 6 weeks, and 8 weeks.
  • Efficacy evaluation method The eye image of the subject was photographed for 0 days as a reference material, and images were taken for 2, 4, 6 and 8 weeks.
  • the photoshop software Lab system was used for colorimetric analysis.
  • the L value was used to indicate the whiteness of the eye skin. The higher the L value, the whiter the skin.
  • the SPSS statistical results were used to evaluate the efficacy of the product, P ⁇ 0.1 It is considered to be statistically significant.
  • Pairwise comparison 1 Composition 1 (basic formula) versus composition 2 (basic formula + 0.5% neohesperidin);
  • Pairwise comparison 2 Composition 1 (basic formula) versus composition 3 (basic formula + 2% neohesperidin);
  • Pairwise comparison 3 Composition 1 (basic formula) versus composition 4 (basic formula + 10% neohesperidin extract).
  • the basic formula of the active ingredient is also changed. Deducting this change helps to provide the accuracy of the test.
  • Reasons for this change in the base formula may include, but are not limited to, non-objective factors such as the stimulating effects of the base formula itself, the heat and cold stimuli, mood, and the brightness of the shooting environment. These factors may cause the L value to change, thereby reducing the objectivity of the test results, so the experimental strip needs to be strictly controlled during the experiment. Pieces. Setting the left and right eye self-controls in the experimental method can eliminate or balance the influence of irrelevant variables during the experiment to the greatest extent. Therefore, the difference between the experimental group and the control group can be regarded as the effect from the experimental variables.
  • the test results show that the L value on the side of the smear-based formulation has different degrees of increase in different test times, indicating that non-objective factors have a certain influence on the L value under the experimental conditions, and the smear is added.
  • the L value on the side of the new hesperidin increased to a greater extent, was significant compared to the former, and indicated that the significance was due to the effect of neohesperidin.
  • Table 4B compares the average improvement of 2 pairs of black eyelids in pairs
  • the base formula +10% new hesperidin extract provided significantly greater improvement than the base formulation at 2 weeks of use (P ⁇ 0.05).
  • neohesperidin can be used to improve skin microcirculation, particularly periocular skin microcirculation, particularly as a cosmetic skin care product for removing dark eyelids.
  • compositions of the present invention which can be processed in a conventional manner. They are suitable for cosmetic skin care applications, in particular the compositions are suitable for removing dark eyelids to improve the appearance and feel of the eye skin.

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Abstract

本发明公开了新橙皮苷或包含新橙皮苷的植物提取物在制备用于改善和/或促进皮肤微循环,或者消除和/或缓解与皮肤微循环不良有关的病症或状态的产品中的用途。本发明还公开了包含有效量的新橙皮苷或包含新橙皮苷的植物提取物的组合物。本发明还公开了新橙皮苷可以有益于皮肤微循环特别是眼部皮肤微循环。

Description

新橙皮苷的新用途 技术领域
本发明涉及新橙皮苷的新用途, 特别是在化妆品方面的新用 途, 更特别是新橙皮苷作为改善皮肤微循环的化学成分的作用,特 别是在用于祛除眼部黑眼圏方面的新用途。 背景技术
人体眼部皮肤的构造有别于人体肌肤的其它部位,首先眼部周 围的颧骨之上和鼻梁两旁是血管和淋巴的 "输送位点",该部位是面 部微静脉交汇的场所, 并且血管非常幼细而丰富, 若眼部微循环不 足, 将导致血液循环不畅或组织水肿造成血液瘀肿、 水分围积; 同 时, 眼部周围的皮肤非常薄仅为其他部位皮肤厚度的 1/10,通过光 线折射后极易在眼周出现紫黑色, 形成黑眼圏。 而疲劳、 压力、 睡 眠不足等原因, 是导致微循环障碍的重要因素, 加之年岁渐长, 肌 肤每十年就会减少约 6%的厚度, 黑眼圏将更加明显。 因此无论短 暂的或长期的,不同年龄的女性都曾经或一直有被黑眼圏问题所困 扰的经历, 需通过改善眼周肌肤的微循环加以改善。
文献报道很多天然植物提取物经口服和静脉等途径应用后可 以显著改善皮肤的微循环, 如: 红花提取物、 丹参提取物、 银杏叶 提取物、 假叶树提取物、金雀花提取物、 柑橘提取物、 人参提取物 等。同时也有文献报道了从上述植物提取物中提取纯化到的一些单 体成分如丹参酮、 人参皂甙、 β-七叶皂苷、 鲁斯可皂苷、 银杏黄酮 等局部外用于人体皮肤后对微循环的作用,结果表明这些化学物质 经局部施用于皮肤表面后均不能显著改善皮肤微循环。
目前市面上所售的改善皮肤微循环 (例如改善眼部皮肤微循 环, 例如祛除黑眼圏)的眼部产品层出不穷, 大多是添加了一些植 物提取物,但是一方面这些提取物中是何种或何类成分发挥效果不 明确, 另一方面这些产品祛除黑眼圏的效果并不明显, 大多数改善 皮肤微循环 (例如用于祛黑眼圏)的产品经消费者使用后并未产生 预期的效果 (例如祛黑眼圏功效)。 因此寻找经局部外用后能显著改 善皮肤微循环的化学物质, 用以开发改善皮肤微循环 (例如改善眼 部皮肤微循环, 例如祛除黑眼圏)的产品, 特别是祛除黑眼圏的眼 部护理产品, 仍是本领域人员重点研究的方向。
新橙皮苷是一种二氢黄酮,来源于芸香科枳属植物枳 (拉丁名:
Poncirus trifoliata(L.) 下:
Figure imgf000003_0001
分子式 C28H34015, 分子量 610.56。 主要用于二氢查尔酮类新 型甜味剂的制备。据文献报道,新橙皮苷在抗过敏方面具有一定的 疗效, 而关于新橙皮苷在改善皮肤微循环方面的用途尚未见有报 道。开发新的具有改善皮肤微循环作用的产品特别是具有改善眼部 皮肤微循环作用的产品, 仍是本领域技术人员期待的。 发明内容
本发明的目的在于提供新橙皮苷在改善皮肤微循环 (例如改善 眼部皮肤微循环, 例如祛除黑眼圏)的方面的新用途。 本发明令人 意外地发现,使用新橙皮苷或者包含新橙皮苷的植物提取物可以有 效地改善皮肤微循环,特别是改善眼部皮肤微循环, 更特别是可以 有效地祛除黑眼圏。 本发明基于上述发现而得以完成。
发明概述:
为此,本发明第一方面提供了新橙皮苷或包含新橙皮苷的植物 提取物在制备用于改善和 /或促进皮肤微循环, 或者消除和 /或緩解 与皮肤微循环不良有关的病症或状态的产品中的用途。例如在用于 改善和 /或促进哺乳动物 (特别是人的)皮肤微循环, 或者消除和 /或 緩解与哺乳动物 (特别是人的)皮肤微循环不良有关的病症或状态 的产品中的用途。
根据本发明第一方面的用途,其中所述皮肤微循环是眼部皮肤 微循环。
根据本发明第一方面的用途,其中所述与皮肤微循环不良有关 的病症或状态是指与眼部皮肤微循环不良有关的病症或状态。
根据本发明第一方面的用途,其中所述与眼部皮肤微循环不良 有关的病症或状态是指黑眼圏。
根据本发明第一方面的用途,其中所述包含新橙皮苷的植物提 取物是指由芸香科枳属植物枳(Poncirus trifoliata(L.)Raf.)的果实 提取获得的提取物。
根据本发明第一方面的用途,其中所述包含新橙皮苷的植物提 取物是指由芸香科枳属植物枳(Poncirus trifoliata(L.)Raf.)的果实 提取获得的提取物, 并且该提取物中新橙皮苷含量不低于 50 重 量%。 在一个优选实施方案中, 该提取物中新橙皮苷含量达到 60 重量%以上、 70重量%以上、 80重量%以上、 85重量%以上、 90 重量%以上、 或 95重量%以上。
根据本发明第一方面的用途, 其中所述产品是局部施用的产 品。
根据本发明第一方面的用途,其中所述产品是皮肤外用的局部 施用的产品。
根据本发明第一方面的用途,其中所述产品是用于眼部皮肤的 局部施用的产品。
根据本发明第一方面的用途, 其中所述产品是化妆品。
根据本发明第一方面的用途, 其中所述产品是呈溶液、 乳状、 膏状、 乳膏、 或凝胶的形式。
根据本发明第一方面的用途, 其中所述产品中包含: (1)新橙 皮苷或包含新橙皮苷的植物提取物, 和 (2)生理学可接受的赋形剂。
根据本发明第一方面的用途, 其中所述产品中包含: (1)新橙 皮苷或包含新橙皮苷的植物提取物, 和 (2)生理学可接受的赋形剂; 并且其中所述新橙皮苷或包含新橙皮苷的植物提取物占该产品总 重量的百分数以新橙皮苷计为 0.01-20重量%。在一个实施方案中。 所述新橙皮苷或包含新橙皮苷的植物提取物占该产品总重量的百 分数以新橙皮苷计为 0.01-15重量。 /0、 0.01-10重量。 /0、 0.05-15重 量%、 0.1-10重量%、 0.2-10重量%、 或 0.2-5重量%。
本发明第二方面提供一种组合物, 其包含: (1)有效量的新橙 皮苷或包含新橙皮苷的植物提取物, 和任选的 (2)生理学可接受的 赋形剂。
根据本发明第二方面的组合物, 其包含: (1)有效量的新橙皮 苷或包含新橙皮苷的植物提取物, 和任选的 (2)生理学可接受的赋 形剂;并且其中所述新橙皮苷或包含新橙皮苷的植物提取物占该组 合物总重量的百分数以新橙皮苷计为 0.01-20重量%。 在一个实施 方案中。所述新橙皮苷或包含新橙皮苷的植物提取物占该组合物总 重量的百分数以新橙皮苷计为 0.01-15 重量%、 0.01-10 重量。 /0、 0.05-15重量%、 0.1-10重量%、 0.2-10重量%、 或 0.2-5重量%。
根据本发明第二方面的组合物,其中所述包含新橙皮苷的植物 提取物是指由芸香科枳属植物枳(Poncirus trifoliata(L.)Raf.)的果 实提取获得的提取物。
根据本发明第二方面的组合物,其中所述包含新橙皮苷的植物 提取物是指由芸香科枳属植物枳(Poncirus trifoliata(L.)Raf.)的果 实提取获得的提取物, 并且该提取物中新橙皮苷含量不低于 50重 量%。 在一个优选实施方案中, 该提取物中新橙皮苷含量达到 60 重量%以上、 70重量%以上、 80重量%以上、 85重量%以上、 90 重量%以上、 或 95重量%以上。
根据本发明第二方面的组合物, 其是用作改善和 /或促进皮肤 微循环 , 或者消除和 /或緩解与皮肤微循环不良有关的病症或状态 的产品。 在一个实施方案中, 所述皮肤微循环是眼部皮肤微循环。 在一个实施方案中,所述与皮肤微循环不良有关的病症或状态是指 与眼部皮肤微循环不良有关的病症或状态。在一个实施方案中, 其 中所述与眼部皮肤微循环不良有关的病症或状态是指黑眼圏。
根据本发明第二方面的组合物, 其是用作局部施用的产品。 根据本发明第二方面的组合物,其是用作皮肤外用的局部施用 的产品。
根据本发明第二方面的组合物,其是用作眼部皮肤的局部施用 的产品。
根据本发明第二方面的组合物, 其是化妆品。
根据本发明第二方面的组合物, 其是呈溶液、 乳状、 膏状、 乳 膏、 或凝股的形式。
本发明第三方面提供在有需要的个体中改善和 /或促进皮肤微 循环 , 或者消除和 /或緩解与皮肤微循环不良有关的病症或状态的 方法,该方法包括给该个体施用有效量的新橙皮苷或包含新橙皮苷 的植物提取物。
根据本发明第三方面的方法,其中所述皮肤微循环是眼部皮肤 微循环。 根据本发明第三方面的方法,其中所述与皮肤微循环不良有关 的病症或状态是指与眼部皮肤微循环不良有关的病症或状态。
根据本发明第三方面的方法,其中所述与眼部皮肤微循环不良 有关的病症或状态是指黑眼圏。
根据本发明第三方面的方法,其中所述包含新橙皮苷的植物提 取物是指由芸香科枳属植物枳(Poncirus trifoliata(L.)Raf.)的果实 提取获得的提取物。
根据本发明第三方面的方法,其中所述包含新橙皮苷的植物提 取物是指由芸香科枳属植物枳(Poncirus trifoliata(L.)Raf.)的果实 提取获得的提取物, 并且该提取物中新橙皮苷含量不低于 50 重 量%。 在一个优选实施方案中, 该提取物中新橙皮苷含量达到 60 重量%以上、 70重量%以上、 80重量%以上、 85重量%以上、 90 重量%以上、 或 95重量%以上。
根据本发明第三方面的方法,其中所述有效量的新橙皮苷或包 含新橙皮苷的植物提取物是以局部施用的产品的形式施用的。
根据本发明第三方面的方法,其中所述有效量的新橙皮苷或包 含新橙皮苷的植物提取物是以皮肤外用的局部施用的产品的形式 施用的。
根据本发明第三方面的方法,其中所述有效量的新橙皮苷或包 含新橙皮苷的植物提取物是以用于眼部皮肤的局部施用的产品的 形式施用的。
根据本发明第三方面的方法,其中所述有效量的新橙皮苷或包 含新橙皮苷的植物提取物是以化妆品的形式施用的。
根据本发明第三方面的方法,其中所述有效量的新橙皮苷或包 含新橙皮苷的植物提取物是以呈溶液、 乳状、 膏状、 乳膏、 或凝胶 的形式施用的。
本发明任一方面或该任一方面的任一具体实施方案所具有的 特征同样适用于该方面的其它任一具体实施方案,也同样适用于其 它任一方面或其它任一方面的任一具体实施方案。
发明详迷:
下面对本发明的各个方面和特点作进一步的描述。
本发明所引述的所有文献, 它们的全部内容通过引用并入本 文, 并且如果这些文献所表达的含义与本发明不一致时, 以本发明 的表述为准。此外,本发明使用的各种术语和短语具有本领域技术 人员公知的一般含义, 即便如此,本发明仍然希望在此对这些术语 和短语作更详尽的说明和解释,提及的术语和短语如有与公知含义 不一致的, 以本发明所表述的含义为准。
如本文所述的, 术语 "皮肤微循环" , 是指皮肤真皮层下的微 血管网, 是循环的终末部分, 属于毛细血管, 是动静脉交接点, 是 血液与组织细胞进行物质交换的场所。皮肤微循环是一个复杂的动 力系统, 对皮肤颜色、 温度调节、 皮肤代谢和透皮转运起着非常重 要的作用, 直接影响皮肤的健康。
如本文所述的,术语"与皮肤微循环不良有关的病症或状态", 是指由于皮肤局部微循环不良或障碍而出现的病理性或非病理性 的身体状态或者异常情况, 例如皮炎、 色素沉着、 皮肤老化、 皮肤 苍白、 红血丝、 局部皮肤瘀肿、 局部水分囤积、 黑眼圏等。
如本文所述的, 术语 "改善"、 "促进"、 "消除" "緩解", 例如 本文所述 "改善和 /或促进皮肤微循环" 和 "消除和 /或緩解与皮肤 微循环不良有关的病症或状态", 是指使由于皮肤局部微循环不良 或障碍而出现病理性或非病理性的身体状态或者异常情况产生有 益的作用, 例如改善皮肤局部微循环、促进皮肤局部微循环、 消除 由于皮肤局部微循环不良或障碍而出现病理性或非病理性的身体 状态或者异常情况、緩解由于皮肤局部微循环不良或障碍而出现病 理性或非病理性的身体状态或者异常情况。例如改善红血丝、 消除 色素沉着、 消除水肿、 緩解瘀肿、 消除黑眼圏等。
如本文所述的, 术语 "生理学可接受的" 是指生理学相容的, 特别是皮肤外用产品中使用的与皮肤接触时可以使用的,例如不产 生对皮肤的刺激性等副作用。特别是例如化妆品中可以使用的稀释 剂、 表面活性剂、 增稠剂、 润肤剂等。
如本文所述的, 术语 "有效量" 是指可在受试者中实现治疗、 预防、 减轻和 /或緩解本发明所述疾病或病症的剂量。
如本文所述的, 术语 "组合物", 其还可以是指 "化妆品"、 "化 妆品组合物"、 "药物组合物", 其可用于在个体中实现治疗、预防、 减轻和 /或緩解本发明所述疾病、 病症、 或身体状态。
如本文所述的, 术语 "个体" , 其还可以是指 "受试者"、 "患 者" 或者其它接受本发明组合物以改善和 /或促进其出现的皮肤微 循环, 或者消除和 /或緩解其出现的与皮肤微循环不良有关的病症 或状态的动物, 特别是哺乳动物, 例如人、 狗、 猴、 牛、 马等, 特别是人。
如本文所述的, 术语 "眼部皮肤微循环"是指眼睛周围的皮肤 中的微循环。
根据本发明 , 所述新橙皮苷可由芸香科枳属植物枳 (Poncirus trifoliata(L.)Raf.)的果实提取获得, 也可以根据本领域已知的化学 方法合成或经生物转化而得。该新橙皮苷可以是单体化合物,也可 以是新橙皮苷含量不低于 50%(w/w)的提取物。 在本发明中, 以新 橙皮苷单体化合物使用量计, 新橙皮苷以 0.01%-20%(w/w)、 优选 0.05%-15%(w/w), 最优选 0.1%-10%(w/w)的浓度用于本发明的组 合物中。
本发明也包括含新橙皮苷的化妆品护肤组合物。
本发明涉及一种化妆品护肤组合物, 该组合物包括: (1)以 0.1%-10%重量的量存在的新橙皮苷; 和 (2)化妆品中可接受的媒介 物。
在本发明的组合物中使用新橙皮苷是为了达到祛除眼部黑眼 圏的效果。
本发明的组合物和方法还包括化妆品中可接受的媒介物来作 为组合物中活性成分的稀释剂、分散剂或载体,从而当组合物用于 皮肤时促进其分布。
外的媒介物包括液体或固体润肤剂、 表面活性剂、 溶剂、
Figure imgf000010_0001
各种类型的活性成分都可存在于本发明的化妆品组合物中。活 性物质被定义为不同于润肤剂和仅改善组合物的物理性能的成分 的物质。
在本发明的一个实施方案中,提供了一种具有如下配方的组合 物:
成分 重量比
甲基葡糖倍半硬脂酸酯 0.5-5 wt%,
二曱基硅氧烷 0.5-5 wt%,
十六 /十八醇 1-5 wt%,
碳酸二辛酯 2-8 wt%,
辛酸丙基庚酯 1-5 wt%,
软磷脂 1-5 wt%,
汉生胶 0.1-2 wt%,
1,3丁二醇 1-10 wt%,
EDTA-2Na 0.1-2 wt%,
甘油 1-5 wt%,
三乙醇胺 1-5 wt%,
乳酸 适量, 调 pH值至 4.0~6.0
防腐剂 适量
0.01-20重量%、 0.01-15重量%、 0.01-10重 新橙皮苷或包含新橙皮苷
量%、 0.05-15重量%、 0.1-10重量%、 0.2-10 的提取物
重量%、 或 0.2-5重量% (以新橙皮苷计) 水 加至 100% 按照本发明,通过局部应用新橙皮苷, 可达到减少或消除眼部 黑眼圏的作用。
本发明涉及新橙皮苷在化妆品方面的新用途,特别是新橙皮苷 作为改善皮肤微循环的化学成分在祛除眼部黑眼圏方面的新用途。 优选在该用途中, 所述新橙皮苷以占组合物 0.01%-10%重量的量 存在。
为了更好地利用新橙皮苷,本发明对新橙皮苷局部施用于皮肤 表面的促微循环效果进行了研究,结果表明新橙皮苷局部外用后可 明显改善皮肤微循环,本发明人将其应用于眼部护理产品中,发现 新橙皮苷具有明显地祛除黑眼圏的作用。 具体实施方式
通过下面的实例可以对本发明进行进一步的描述, 然而, 本发 明的范围并不限于下述实例。 本领域的专业人员能够理解,在不背 离本发明的精神和范围的前提下, 可以对本发明进行各种变化和 修饰。
本发明对试验中所使用到的材料以及试验方法进行一般性和 /或具体的描述。 虽然为实现本发明目的所使用的许多材料和操作 方法是本领域公知的,但是本发明仍然在此作尽可能详细的描述。 在本发明的上下文中, 如果无其它特别的说明, %表示 wt%, 即 重量百分数。 实施例 1: 用激光多普勒观察局部外用新橙皮苷对皮肤微循环 的影响
促微循环试验方法: 取体重为 3.0-3.5kg雄性日本大耳白兔, 背部剃毛后, 用记号笔在兔子无毛区划定测试血流的 10个点, 左 右侧各 5个点, 画点避开大血管; 涂样品前, 用激光多普勒血流仪 测定各组实验兔子 10点的血流基础值, 各组兔子背部左侧涂抹空 白溶液, 右侧涂抹含新橙皮苷的溶液 (三组动物, 药液浓度分别为
0.5%(w/v)、 l%(w/v)、 2%(w/v), 每动物用量 0.1毫升), 每个浓度 样品平行 3 只兔子。 以类似方法口服 2%(w/v)的药液, 用药量为 2%(w/v)药液涂抹组的 100倍。 用药后每经 1小时用激光多普勒血 流仪测定相同部位的血流值, 共测定 24小时, 并计算血流变化指 数,评价新橙皮苷对兔子背部血流的影响,血流变化指数越高表示 促进微循环作用效果越好。 实验结果用 SPSS11.5软件进行统计分 析, 计量资料应用 t检验评价试验结果, P < 0.1即可被认为具有统 计显著性。 在表 1的结果中列出了在 24小时的测试中, 出现 P < 0.1的全部时间点。
不同浓度新橙皮苷促进家兔皮肤微循环的作用
Figure imgf000012_0001
注: 表中 "一" 表示以 2%药液口服时, 在 24小时的测试中, 未出现 P < 0.1的时间点。
试验结果表明, 兔子背部涂抹含不同浓度新橙皮苷的样品后, 与空白侧相比, 能显著提高兔子皮肤微血管血流。 实施例 2: 新橙皮苷祛除眼部黑眼圏的效果
方法: 本研究采用 8周两种配方两侧眼部对比使用试验。 在本研究中招募了中重度黑眼圏志愿者 50名, 保证每个成对 比较组有效人数为 15人。 在受试者间随机分配并左 /右平衡使用, 眼部一侧涂抹含新橙皮苷的组合物,另一侧涂抹不含新橙皮苷的组 合物, 持续 8周。 在 0周 (处理前)、 2周、 4周、 6周和 8周对其祛 除黑眼圏效果进行功效评价。
功效评价方法: 试验 0 天拍摄受试者的眼部图像作为基准资 料, 试验 2、 4、 6和 8周进行图像拍摄。 采用 photoshop软件 Lab 系统进行色度分析计算, 以 L值表示眼部肌肤白度, L值越高说明 皮肤越白, 与基准资料对比分析, SPSS统计结果用以评定产品功 效, P < 0.1即可被认为具有统计显著性。
测试者使用表 2中的基础配方和表 3中的组合物进行测试。 表 2 基础配方
成分 重量比
甲基葡糖倍半硬脂酸酯 1.2%
二曱基硅氧烷 1.0%
十六 /十八醇 3%
碳酸二辛酯 4%
辛酸丙基庚酯 2%
软磷脂 2.5%
汉生胶 0.3%
1,3丁二醇 4%
EDTA-2Na 0.2%
甘油 2.0%
三乙醇胺 2%
乳酸 适量, 调 pH值至 4.0~6.0
防腐剂 适量
水 加至 100% 表 3 组合物
Figure imgf000014_0001
进行以下成对比较:
成对比较 1:组合物 1(基础配方)对组合物 2(基础配方 +0.5%新 橙皮苷);
成对比较 2: 组合物 1(基础配方)对组合物 3(基础配方 +2%新 橙皮苷);
成对比较 3: 组合物 1(基础配方)对组合物 4(基础配方 +10%新 橙皮苷提取物)。
获得的结果列于表 4A至 4C:
Figure imgf000014_0002
"基础配方 +0.5%新橙皮苷在使用 6周开始提供了比基础配方 显著更大的改善 (P < 0.05)。
#无活性成分的基础配方亦出现变化, 扣除此变化有助于提供 试验的准确性。 出现此基础配方出现变化的原因可能包括但不限 于: 基础配方本身的刺激作用、 受冷热刺激、 情绪、 以及拍摄环境 明暗度等非客观因素。 这些因素均可能会导致 L值发生变化, 从 而降低测试结果的客观性, 因此在实验过程中需严格控制实验条 件。在实验方法中设置左右眼自身对照, 可以最大程度地消除或平 衡实验过程中无关变量的影响, 因此实验组与对照组两者之差异, 可认定为是来自实验变量的效果。如在本实施例中, 测试结果表明 涂抹基础配方一侧的 L值在不同测试时间内均有不同程度的增加, 说明在该实验条件下非客观因素对 L值有一定的影响, 而涂抹添 加新橙皮苷一侧的 L值增加的程度更高, 与前者相比具有显著性, 并且说明该显著性是新橙皮苷的效果所致。 表 4B 成对比较 2对黑眼圏的平均改善
Figure imgf000015_0001
"基础配方 +2%新橙皮苷在使用 4周开始提供了比基础配方 显著更大的改善 (P < 0.05)。 表 4C 成对比较 3对黑眼圏的平均改善
Figure imgf000015_0002
基础配方 +10%新橙皮苷提取物在使用 2周开始提供了比基 础配方显著更大的改善 (P < 0.05)
以上成对比较结果表明,组合物中添加了新橙皮苷后, 与不添 加新橙皮苷的组合物相比,具有显著地改善黑眼圏的作用。该实施 例说明新橙皮苷可用于改善皮肤微循环特别是眼周皮肤微循环,特 别在用作祛除黑眼圏的化妆品护肤产品。
以上实施例说明了本发明的局部用组合物,所述组合物可以以 常规方式加工。 它们适合于化妆护肤用途,具体来说所述组合物适 合用于祛除黑眼圏以改善眼部皮肤外观和感觉。

Claims

权 利 要 求
1. 新橙皮苷或包含新橙皮苷的植物提取物在制备用于改善和 / 或促进皮肤微循环, 或者消除和 /或緩解与皮肤微循环不良有关的 病症或状态的产品中的用途。
2. 根据权利要求 1的用途,其中所述皮肤微循环是眼部皮肤微 循环。
3. 根据权利要求 1至 2任一项的用途,其中所述与皮肤微循环 不良有关的病症或状态是指与眼部皮肤微循环不良有关的病症或 状态。
4. 根据权利要求 1至 3任一项的用途,其中所述与眼部皮肤微 循环不良有关的病症或状态是指黑眼圏。
5. 根据权利要求 1至 4任一项的用途,其中所述包含新橙皮苷 的植物提取物是指由芸香科枳属植物枳 (Poncirus trifoliata(L.)Raf.) 的果实提取获得的提取物。
6. 根据权利要求 1至 5任一项的用途,其中所述产品是局部施 用的产品。
7. 根据权利要求 1至 6任一项的用途, 其中所述产品中包含: (1)新橙皮苷或包含新橙皮苷的植物提取物, 和 (2)生理学可接受的 赋形剂。
8. 一种组合物,其包含: (1)有效量的新橙皮苷或包含新橙皮苷 的植物提取物, 和任选的 (2)生理学可接受的赋形剂。
9. 根据权利要求 8的组合物,其包含: (1)有效量的新橙皮苷或 包含新橙皮苷的植物提取物, 和任选的 (2)生理学可接受的赋形剂; 总重量的百分数以新橙皮苷计为 0.01-20重量。 /0,
10. 根据权利要求 8至 9任一项的组合物,其中所述包含新橙皮 苷的植物提取物是指 由 芸香科枳属植物枳(Poncirus trifoliata(L.)Raf.)的果实提取获得的提取物。
11. 根据权利要求 8至 10任一项的组合物, 其是用作改善和 /或 促进皮肤微循环, 或者消除和 /或緩解与皮肤微循环不良有关的病 症或状态的产,品,
12. 根据权利要求 8至 10任一项的组合物, 其是用作局部施用 的产品。
PCT/CN2011/082950 2011-11-25 2011-11-25 新橙皮苷的新用途 WO2013075333A1 (zh)

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