WO2022110550A1 - 一种功效促进组合物及其应用 - Google Patents

一种功效促进组合物及其应用 Download PDF

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WO2022110550A1
WO2022110550A1 PCT/CN2021/075783 CN2021075783W WO2022110550A1 WO 2022110550 A1 WO2022110550 A1 WO 2022110550A1 CN 2021075783 W CN2021075783 W CN 2021075783W WO 2022110550 A1 WO2022110550 A1 WO 2022110550A1
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salt
hyaluronic acid
composition
weight
mass percentage
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PCT/CN2021/075783
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English (en)
French (fr)
Inventor
蔺虓霄
阚洪玲
林伶俐
董建军
邵萌
王磊
田雪
郭学平
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华熙生物科技股份有限公司
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Priority to KR1020237019821A priority Critical patent/KR20230107323A/ko
Priority to JP2023532218A priority patent/JP2023552126A/ja
Publication of WO2022110550A1 publication Critical patent/WO2022110550A1/zh

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    • 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
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/735Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • 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
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/345Alcohols containing more than one hydroxy group
    • 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
    • A61K8/40Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • 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
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • 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
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • 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
    • A61K8/9728Fungi, e.g. yeasts
    • 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]
    • A61K8/9794Liliopsida [monocotyledons]
    • 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
    • A61Q19/007Preparations for dry skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52Stabilizers
    • A61K2800/524Preservatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/85Products or compounds obtained by fermentation, e.g. yoghurt, beer, wine

Definitions

  • the invention belongs to the field of biomedicine, and in particular relates to an efficacy promoting composition and application thereof.
  • the prerequisite for the maximum effect of cosmetics is that the active ingredients have good permeability and activity, and improve the utilization rate of active ingredients.
  • Transdermal absorption of cosmetics refers to the process in which functional ingredients in cosmetics act on the surface of the skin or enter the epidermis or dermis according to the effectiveness of the product, and accumulate and play a role in this part.
  • the transdermal absorption of cosmetic functional ingredients does not need to enter the systemic circulation through the skin, which is the main difference between it and drugs.
  • an efficacy-promoting composition which can not only promote the penetration and absorption of the active ingredients according to the different positions where different functional ingredients play their roles, enable the active ingredients to achieve precise positioning, quickly exert skin care effects, but also improve the stability of the functional ingredients. , to increase the contact time between the functional ingredients and the skin, thereby improving the utilization rate of the functional ingredients.
  • the purpose of the present invention is to provide an efficacy promoting composition, which can effectively improve the penetration and absorption of functional components and the stability of functional components while moisturizing and replenishing water, thereby improving the utilization rate of functional components and improving skin condition.
  • the present invention relates to the following aspects:
  • compositions for promoting efficacy characterized in that the composition comprises macromolecular hyaluronic acid or its salt, hydrolyzed hyaluronic acid or its salt, acetylated hyaluronic acid or its salt, tetrahydropyrimidine or its derivatives substances, ergothioneine, yeast/rice fermentation product filtrate, aminobutyric acid.
  • the composition according to item 1 characterized in that, in the composition, the mass percentage of the polymer hyaluronic acid or its salt is 1-30%, preferably 1-10%, and the hydrolysis
  • the mass percentage of hyaluronic acid or its salt is 2%-50%, preferably 2-10%, and the mass percentage of the acetylated hyaluronic acid or its salt is 1-10%, preferably 1-1.5%, so
  • the mass percentage of the tetrahydropyrimidine or its derivative is 0.1%-10%, preferably 0.3-5%
  • the mass percentage of the ergothioneine is 2-20%, preferably 3-10%
  • the mass percentage of the bacteria/rice fermentation product filtrate is 10-50%, preferably 15-40%, and the mass percentage of the aminobutyric acid is 0.1-5%, preferably 0.3-3%.
  • composition according to item 1 or 2 characterized in that, in parts by weight, the polymer hyaluronic acid or its salt is 1 part by weight, and the hydrolyzed hyaluronic acid or its salt is 0.2-2
  • the weight part is preferably 0.5-1 weight part
  • the acetylated hyaluronic acid or its salt is 0.05-1.5 weight part, preferably 0.1-0.5 weight part.
  • composition according to any one of items 1 to 6, wherein the tetrahydropyrimidine or its derivative is selected from one of tetrahydromethylpyrimidinecarboxylic acid and hydroxytetrahydromethylpyrimidinecarboxylic acid one or two, preferably tetrahydromethylpyrimidine carboxylic acid.
  • composition according to any one of items 1-7, characterized in that, the composition further comprises a preservative, and the mass percentage of the preservative in the composition is 0.1-5%, the The preservative is selected from one or more of pentanediol, hexylene glycol, butanediol and ethylhexylglycerin.
  • a skin care product or cosmetic comprising the composition of any one of items 1-8.
  • Acetylated hyaluronic acid connects polymer hyaluronic acid with specific molecular weight and hydrolyzed hyaluronic acid in a specific ratio to build a stable "I"-shaped channel in three-dimensional space, forming a moisturizing and water-locking layer from the skin surface to the skin
  • the long-term moisturizing channel of the deep moisturizing layer can effectively replenish moisture and increase skin moisture content
  • the "G"-shaped efficacy promotion system constructed with 7 ingredients can improve the stability of macromolecular functional ingredients and increase the contact time with the skin while moisturizing and repairing the skin, thereby improving the utilization of macromolecular functional ingredients. On the other hand, it can increase the transdermal absorption effect of small-molecule functional components through the "I"-shaped channel, and increase the small molecular weight. The availability of molecular efficacy components.
  • the mass percentage of the polymer hyaluronic acid or its salt is 1-30%, for example, it can be 1%, 5%, 10%, 15%, 20%, 25%, 30% , preferably 1-10%.
  • the mass percentage of the hydrolyzed hyaluronic acid or its salt is 2%-50%, for example, it can be 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% %, 50%, preferably 2-10%
  • the mass percentage of the acetylated hyaluronic acid or its salt is 1-10%, such as 1%, 1.2%, 1.5%, 2%, 3%, 4% %, 5%, 6%, 7%, 8%, 9%, 10%, preferably 1-1.5%.
  • the mass percentage of the tetrahydropyrimidine or its derivative is 0.1%-10%, for example, it can be 0.1%, 0.3%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, preferably 0.3-5%.
  • the mass percentage of the ergothioneine is 2-20%, can be 2%, 3%, 5%, 10%, 15%, 20%, preferably 3-10%.
  • the mass percentage of the yeast/rice fermentation product filtrate is 10-50%, such as 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, preferably 15-40%.
  • the mass percentage of the aminobutyric acid is 0.1-5%, such as 0.1%, 0.3%, 0.5%, 1%, 2%, 3%, 4%, 5%, preferably 0.3-3%.
  • Hyaluronic Acid is a kind of macromolecular polysaccharide that naturally exists in the interstitial species of human tissues and cells. It is widely used in medicine, skin care products, food and other fields. It has a variety of different molecular weights. HA has different functions and performances. High-molecular HA has excellent film-forming and water-locking functions. Low-molecular hydrolyzed HA can penetrate the skin and deeply hydrate the skin. Acetylated HA can be used as a bridge connecting the skin surface and hydrolyzed HA. , is a natural and effective moisturizing factor and water-locking factor.
  • the molecular weight of the high molecular weight hyaluronic acid or its salt is 1000-1800kDa, for example, it can be 1000kDa, 1100kDa, 1200kDa, 1300kDa, 1400kDa, 1500kDa, 1600kDa, 1700kDa, 1800kDa, preferably 1000- 1500kDa.
  • the molecular weight of the hydrolyzed hyaluronic acid or its salt is 1kDa-10kDa, such as 1kDa, 2kDa, 3kDa, 4kDa, 5kDa, 6kDa, 7kDa, 8kDa, 9kDa, 10kDa, preferably 5kDa-10kDa.
  • the molecular weight of the acetylated hyaluronic acid or its salt is 20kDa-100kDa, for example, it can be 20kDa, 30kDa, 40kDa, 50kDa, 60kDa, 70kDa, 80kDa, 90kDa, 100kDa.
  • the mass percentage of acetyl groups in the acetylated hyaluronic acid or its salt is 20-40%, for example, it can be 20%, 25%, 30%, 35%, 40%.
  • Tetrahydromethylpyrimidine carboxylic acid is the most widely distributed compatible solute found in the bacterial kingdom. It is compatible with intracellular metabolism and does not affect the biological macromolecular or physiological functions of cells. Important osmotic compensation solutes. Due to the dense charge distribution on the surface of Ecto, it can further strengthen the hydrogen bond between water molecules through the electrostatic interaction with water molecules, reduce water activity, complex water molecules, and have a long-term moisturizing effect. Through its own high-density charge, it strengthens the hydrogen bond between water molecules to achieve long-term moisturizing; because it has excellent hydrophilicity, through the above-mentioned I-shaped structure, the skin barrier can be repaired more efficiently. damage.
  • the tetrahydropyrimidine or its derivative is selected from one or both of tetrahydromethylpyrimidine carboxylic acid and hydroxytetrahydromethylpyrimidine carboxylic acid, preferably tetrahydromethylpyrimidine carboxylic acid.
  • Ergothioneine is distributed in some tissues and organs of mammals. It is a natural antioxidant that can be produced by fermentation. It can protect cells in the human body and has UV protection. important active substances in the body. Through the synergistic effect with ECTOIN, it can effectively protect the skin barrier and ensure the operation of the "I"-shaped structure formed by sodium hyaluronate and its derivatives.
  • Aminobutyric acid can promote the proliferation of epidermal cells and the production of keratinocyte involucrin, repair the stratum corneum barrier, reduce UV damage to the skin, and improve cell activity.
  • Ectrahydropyrimidine or its derivatives, ergothioneine, yeast/rice fermented product filtrate, aminobutyric acid can effectively protect the skin barrier and ensure the stability and durability of the film formed by polymer HA on the skin surface, thereby ensuring transparency Efficient operation of the "I"-shaped structure formed by sodium phosphate and its derivatives.
  • the composition also includes a preservative, the preservative is selected from one or more of pentanediol, hexylene glycol, butanediol and ethylhexylglycerol, and the preservative is in the composition.
  • the mass percentage is 0.1-5%.
  • the present invention also provides the application of the above composition in skin care products or cosmetics.
  • the efficacy-promoting composition of the present invention comprises macromolecular hyaluronic acid, hydrolyzed hyaluronic acid, acetylated hyaluronic acid, tetrahydropyrimidine, ergothioneine, yeast/rice fermentation product filtrate and aminobutyric acid in specific proportions, and has Effective efficacy boosts function. For example, it can significantly promote hydration, improve the stability of active ingredients, and improve the absorption of anti-aging ingredients.
  • the materials, reagents, etc. used in the following examples can be obtained from commercial sources unless otherwise specified.
  • high molecular weight sodium hyaluronate, hydrolyzed sodium hyaluronate, acetylated sodium hyaluronate, tetrahydromethylpyrimidine carboxylic acid, ergothioneine, yeast/rice fermentation product filtrate, aminobutyric acid are all from Huaxi Biotechnology Co., Ltd.
  • Example 2 The difference between Examples 2-13, Comparative Examples 1-8 and Example 1 is the molecular weight or content of high molecular weight sodium hyaluronate, hydrolyzed sodium hyaluronate, acetylated sodium hyaluronate, tetrahydromethylpyrimidine carboxylate
  • the contents of acid, ergothioneine, yeast/rice fermentation product filtrate and aminobutyric acid are different, as shown in Table 1.
  • Example 9 and Example 1 is only in the molecular weight of sodium hyaluronate; the difference between Example 10 and Example 1 is only in the content of sodium hyaluronate; Example 11 and Example 1 The difference is only in the content of hydrolyzed sodium hyaluronate; the difference between Example 12 and Example 1 is only in the molecular weight of hydrolyzed sodium hyaluronate; the difference between Example 13 and Example 1 is the amount of acetylated sodium hyaluronate. The content is different.
  • the number of people tested is 10, and the average water content is taken.
  • the comparative examples 1-3 only contain two of the three hyaluronic acids, and the hydrating effect is poor. This may be because the three hyaluronic acids of the present invention can build a stable "I"-shaped channel in the three-dimensional space, It forms a long-term moisturizing channel from the moisturizing and locking layer on the skin surface to the deep moisturizing layer of the skin, which can effectively replenish moisture and increase skin water content.
  • the utilization rate of amide-3 enhances the moisturizing effect.
  • Comparative Examples 4-8 The moisturizing effect of Comparative Examples 4-8 is also poor, among which Comparative Example 8 has the worst moisturizing effect, and the difference in skin water content before and after use is only 0.21, which may be due to tetrahydropyrimidine, ergothioneine, yeast/rice fermentation
  • the synergistic effect of the product filtrate and aminobutyric acid can maintain the stability and durability of the film formed by high molecular hyaluronic acid on the skin surface, thereby ensuring the high efficiency of the "I"-shaped structure formed by sodium hyaluronate and its derivatives. run.
  • test example 2 The protective effect of test example 2 on active ingredients
  • Astaxanthin was added to the efficacy-promoting compositions prepared in Examples 1-13 and Comparative Examples 1-8, so that the mass percentage of astaxanthin in the composition was 0.01% to obtain astaxanthin-containing compositions, which were respectively applied accordingly.
  • Example 1-16 The astaxanthin composition obtained in Example 1 corresponds to Application Example 1, the astaxanthin composition obtained in Example 2 corresponds to Application Example 2, and so on.
  • the astaxanthin composition obtained in Example 8 corresponds to Application Example 8.
  • the astaxanthin composition obtained in Example 13 corresponds to Application Example 13
  • the astaxanthin composition obtained in Comparative Example 1 corresponds to Application Example 14
  • the astaxanthin composition obtained in Comparative Example 2 corresponds to Application Example 15, and the shrimp obtained in Comparative Example 8
  • the cyanin composition corresponds to Application Example 21.
  • Astaxanthin is easily oxidized to lighten the color. The lighter the color, the more oxidized astaxanthin is, and the worse the efficacy of astaxanthin.
  • the color of astaxanthin is not obvious, especially the color change of Examples 1-4 is the smallest, and the absorbance is only reduced by 0.0391-0.0969 compared with the control which is kept in a dark and airtight state.
  • the color of the astaxanthin composition of the comparative example changed greatly, and the absorbance decreased by more than 0.3. This shows that the efficacy promotion system constructed by the seven components of the present invention can improve the stability of macromolecular functional components such as astaxanthin, increase the contact time between astaxanthin and the skin, and thereby improve the utilization rate of astaxanthin.
  • Example 1 Comparative Example 1, and Comparative Example 8, 1% of wrinkle-removing ingredients (anti-wrinkle complex peptide) were added respectively to obtain a composition with anti-aging effect, corresponding to Application Examples 22, 23, and 24, respectively.
  • Application examples 22, 23, and 24 are applied in different areas twice a day for 12 weeks, and the skin age data is recorded with Visia every 2 weeks.
  • test number is 10 people, and the average skin age is taken.
  • the efficacy-promoting composition prepared in the embodiment of the present invention can well promote the efficacy of the anti-aging ingredients. It can be seen from the above table that the efficacy of the anti-aging ingredients in Application Example 22 increases significantly. The skin age was reduced by 6 years, while the skin age of Application Example 23 and Application Example 24 changed little or hardly changed after a period of use.

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Abstract

一种功效促进组合物,其特征在于,所述组合物包括高分子透明质酸或其盐、水解透明质酸或其盐、乙酰化透明质酸或其盐、四氢嘧啶或其衍生物、麦角硫因、酵母菌/大米发酵产物滤液、氨基丁酸。功效促进组合物,对皮肤进行补水修复的同时,一方面可以提高大分子功效成分的稳定性,增加与皮肤的接触时间,从而提高大分子功效成分的利用率,减少功效成分用量,节约成本,并减少某些功效成分用量过多造成的皮肤刺激性;另一方面,又可以增加小分子功效成分的透皮吸收效果,增加小分子功效成分的利用率。

Description

一种功效促进组合物及其应用 技术领域
本发明属于生物医药领域,具体涉及一种功效促进组合物及其应用。
背景技术
化妆品发挥最大功效的前提条件是活性成分具有很好的渗透性和活性,提高活性成分的利用率。
化妆品透皮吸收指的是化妆品中的功能性成分按产品的有效性作用于皮肤表面或进入表皮或真皮,并在该部位积聚和发挥作用的过程。化妆品功效成分的透皮吸收并不需要透过皮肤进入体循环,这是它与药物的主要区别。例如,美白产品中的美白剂需要作用于皮肤的基底层,阻断黑色素的生成;抗衰老产品的功效成分则需作用于真皮层的成纤维细胞,使皮肤富有弹性;防晒产品中的防晒剂需滞留在皮肤表面,吸收和反射紫外线;而一些保湿产品则根据不同作用机理,作用于表皮层或真皮层起到改善皮肤含水量的作用。
影响化妆品透皮吸收的因素很多,主要有:皮肤因素、有效成分结构、物质浓度、化妆品剂型、外界环境等,目前,市面上大多选用与皮肤相似的有效成分、改变化妆品剂型等来提高化妆品的渗透性,效果单一且促渗透作用存在一定的局限性。
因此,迫切需要一种功效促进组合物,根据不同功效成分发挥作用的不同位置,既能促进有效成分的渗透吸收,使有效成分实现精准定位,快速发挥护肤作用,又能提高功效成分的稳定性,增加功效成分与皮肤的接触时间,从而提高功效成分的利用率。
发明内容
本发明的目的在于提供一种功效促进组合物,在保湿补水的同时,可以有效提高功效成分的渗透吸收和功效成分的稳定性,从而提高功效成分的利用率,改善皮肤状况。具体来说,本发明涉及如下方面:
1、一种功效促进组合物,其特征在于,所述组合物包括高分子透明质酸或其盐、水解透明质酸或其盐、乙酰化透明质酸或其盐、四氢嘧啶或其衍生物、麦角硫因、酵母菌/大米发酵产物滤液、氨基丁酸。
2、根据项1所述的组合物,其特征在于,所述组合物中,所述高分子透明质酸或其盐的质量百分比为1-30%,优选为1-10%,所述水解透明质酸或其盐的质量百分比为2%-50%,优选为2-10%,所述乙酰化透明质酸或其盐的质量百分比为1-10%,优选为1-1.5%,所述四氢嘧啶或其衍生物的的质量百分比为0.1%-10%,优选为0.3-5%,所述麦角硫因的质量百分比为2-20%,优选为3-10%,所述酵母菌/大米发酵产物滤液的质量百分比为10-50%,优选为15-40%,所述氨基丁酸的质量百分比为0.1-5%,优选为0.3-3%。
3、根据项1或2所述的组合物,其特征在于,按重量份计,所述高分子透明质酸或其盐为1重量份,所述水解透明质酸或其盐为0.2-2重量份,优选为0.5-1重量份,所述乙酰化透明质酸或其盐为0.05-1.5重量份,优选为0.1-0.5重量份。
4、根据项1-3任一项所述的组合物,其特征在于,所述高分子量透明质酸或其盐的分子量为1000-1800kDa,优选为1000-1500kDa。
5、根据项1-4任一项所述的组合物,其特征在于,所述水解透明质酸的分子量为1kDa-10kDa,优选为5kDa-10kDa。
6、根据项1-5任一项所述的组合物,其特征在于,所述乙酰化透明质酸或其盐的分子量为20kDa-100kDa,乙酰基的质量百分比为20-40%。
7、根据项1-6任一项所述的组合物,其特征在于,所述四氢嘧啶或其衍生物选自四氢甲基嘧啶羧酸和羟基四氢甲基嘧啶羧酸中的一种或两种,优选为四氢甲基嘧啶羧酸。
8、根据项1-7任一项所述的组合物,其特征在于,所述组合物还包括防腐剂,所述防腐剂在所述组合物中的质量百分比为0.1-5%,所述防腐剂选自戊二醇、己二醇、丁二醇和乙基己基甘油中的一种或两种以上。
9、项1-8任一项所述的组合物在护肤品或化妆品中的应用。
10、一种护肤品或化妆品,其包含项1-8任一项所述的组合物。
本发明具有如下有益效果:
1、乙酰化透明质酸以特定的配比连接特定分子量的高分子透明质酸和水解透明质酸,在三维空间内构建稳定的“工”字形通道,形成从皮肤表面保湿锁水层 到皮肤深层补水层的长效补水保湿通道,有效补充水分,增加皮肤含水量;
2、四氢嘧啶、麦角硫因、酵母菌/大米发酵产物滤液和氨基丁酸四者协同作用,保证透明质酸钠及其衍生物形成的“工”字形结构的高效运行,从而更高效率的修复皮肤屏障,修复损伤,改善皮肤表面状况;
3、7种成分构建的“工”字形功效促进体系,对皮肤进行补水修复的同时,一方面可以提高大分子功效成分的稳定性,增加与皮肤的接触时间,从而提高大分子功效成分的利用率,减少功效成分用量,节约成本,并减少某些功效成分用量过多造成的皮肤刺激性;另一方面,又可以通过“工”字形通道增加小分子功效成分的透皮吸收效果,增加小分子功效成分的利用率。
具体实施方式
下面结合实施例进一步说明本发明,应当理解,实施例仅用于进一步说明和阐释本发明,并非用于限制本发明。
除非另外定义,本说明书中有关技术的和科学的术语与本领域内的技术人员所通常理解的意思相同。虽然在实验或实际应用中可以应用与此间所述相似或相同的方法和材料,本文还是在下文中对材料和方法做了描述。在相冲突的情况下,以本说明书包括其中定义为准,另外,材料、方法和例子仅供说明,而不具限制性。以下结合具体实施例对本发明作进一步的说明,但不用来限制本发明的范围。
本发明提供一种功效促进组合物,所述组合物包括高分子透明质酸或其盐、水解透明质酸或其盐、乙酰化透明质酸或其盐、四氢嘧啶或其衍生物、麦角硫因、酵母菌/大米发酵产物滤液、氨基丁酸。
在一个具体的实施方式中,所述高分子透明质酸或其盐的质量百分比为1-30%,例如可以为1%、5%、10%、15%、20%、25%、30%,优选为1-10%。所述水解透明质酸或其盐的质量百分比为2%-50%,例如可以为2%、5%、10%、15%、20%、25%、30%、35%、40%、45%、50%,优选为2-10%,所述乙酰化透明质酸或其盐的质量百分比为1-10%,例如可以为1%、1.2%、1.5%、2%、3%、4%、5%、6%、7%、8%、9%、10%,优选为1-1.5%。所述四氢嘧啶或其衍生物的的质量百分比为0.1%-10%,例如可以为0.1%、0.3%、0.5%、1%、2%、3%、4%、5%、6%、7%、8%、9%、10%,优选为0.3-5%。所述麦角硫因的质量百分 比为2-20%,可以为2%、3%、5%、10%、15%、20%,优选为3-10%。所述酵母菌/大米发酵产物滤液的质量百分比为10-50%,例如可以为10%、15%、20%、25%、30%、35%、40%、45%、50%,优选为15-40%。所述氨基丁酸的质量百分比为0.1-5%,例如可以为0.1%、0.3%、0.5%、1%、2%、3%、4%、5%,优选为0.3-3%。
其中,透明质酸(Hyaluronic Acid,HA)是一种天然存在于人体组织细胞间质种的高分子多糖,广泛应用于医药,护肤品,食品等领域,具有多种不同的分子量,各分子量的HA具有不同的功效与表现,高分子HA具有优秀的成膜与锁水的作用,低分子的水解HA可以渗透皮肤,对皮肤进行深度补水,乙酰化HA可以作为连接皮肤表面与水解HA的桥梁,是一种天然有效的保湿因子及锁水因子。
本发明通过三种不同HA的搭配,在空间中形成以成膜的高分子HA为主的皮肤表面保湿锁水层,以水解HA为主的深层补水层,以及连接两个部分的乙酰化HA的水分输送层,在三维空间内构建“工”字形的长效补水保湿通道。
在一个具体的实施方式中,所述高分子量透明质酸或其盐的分子量为1000-1800kDa,例如可以为1000kDa、1100kDa、1200kDa、1300kDa、1400kDa、1500kDa、1600kDa、1700kDa、1800kDa,优选为1000-1500kDa。所述水解透明质酸或其盐的分子量为1kDa-10kDa,例如可以为1kDa、2kDa、3kDa、4kDa、5kDa、6kDa、7kDa、8kDa、9kDa、10kDa,优选为5kDa-10kDa。所述乙酰化透明质酸或其盐的分子量为20kDa-100kDa,例如可以为20kDa、30kDa、40kDa、50kDa、60kDa、70kDa、80kDa、90kDa、100kDa。所述乙酰化透明质酸或其盐中乙酰基的质量百分比为20-40%,例如可以为20%、25%、30%、35%、40%。
在一个具体的实施方式中,所述高分子透明质酸或其盐为1重量份,所述水解透明质酸或其盐为0.2-2重量份,例如可以为0.2重量份、0.3重量份、0.4重量份、0.5重量份、0.6重量份、0.7重量份、0.8重量份、0.9重量份、1重量份、1.1重量份、1.2重量份、1.3重量份、1.4重量份、1.5重量份、1.6重量份、1.7重量份、1.8重量份、1.9重量份、2重量份,优选为0.5-1重量份,所述乙酰化透明质酸或其盐为0.05-1.5重量份,例如可以为0.05重量份、0.1重量份、0.2重量份、0.3重量份、0.4重量份、0.5重量份、1重量份、1.1重量份、1.2重量份、1.3重量份、1.4重量份、1.5重量份,优选为0.1-0.5重量份。
四氢甲基嘧啶羧酸(ECTOIN)是目前发现的细菌界分布最广泛的相容性溶质,它与细胞内的新陈代谢相容,并不影响细胞的生物大分子功能或生理功能,是一种重要的渗透压补偿溶质。依克多因表面密集的电荷分布,使其可通过与水分子之间的静电作用,进一步强化水分子之间的氢键作用,降低水活性,络合水分子,具有长效保湿的作用。通过自身的高密度电荷,强化水分子之间的氢键作用,做到长效保湿;因为其具有极佳的亲水性,通过上述的工字形结构,可以更高效率的修复皮肤屏障,修复损伤。
在一个具体的实施方式中,所述四氢嘧啶或其衍生物选自四氢甲基嘧啶羧酸和羟基四氢甲基嘧啶羧酸中的一种或两种,优选为四氢甲基嘧啶羧酸。
麦角硫因(ERGOTHIONEINE)分布于哺乳动物的某些组织、器官中,是一种天然抗氧化剂,可通过发酵法生产得到,在人体内可以对细胞起到保护作用,具有UV防护的作用,是机体内的重要活性物质。通过与ECTOIN的协同作用,能够有效的保护皮肤屏障,保证透明质酸钠及其衍生物形成的“工”字形结构的运行。
酵母菌/大米发酵产物滤液(SACCHAROMYCES/RICE FERMENT FILTRATE)是通过发酵法生产的一种天然原料,具有提高细胞活力,促进细胞新生的作用。可以有效通过高分子HA在皮肤表面形成的薄膜,长时间的停留在皮肤表面,促进表面损伤细胞的再生,与麦角硫因及ECTOIN协同作用,更高效的改善皮肤表面状况,增加其保湿能力。
氨基丁酸(AMINOBUTYRIC ACID)可以促进表皮细胞增殖及角质形成细胞外皮蛋白的产生,修复角质层屏障,同时可以减少紫外线对皮肤的损伤,并且可以提高细胞活性。
四氢嘧啶或其衍生物、麦角硫因、酵母菌/大米发酵产物滤液、氨基丁酸能够有效保护皮肤屏障,并保证高分子HA在皮肤表面形成的薄膜的稳定性和持久性,从而保证透明质酸钠及其衍生物形成的“工”字形结构的高效运行。
所述组合物还包括防腐剂,所述防腐剂选自戊二醇、己二醇、丁二醇和乙基己基甘油中的一种或两种以上,所述防腐剂在所述组合物中的质量百分比为0.1-5%。
本发明还提供一种功效促进组合物,所述组合物由高分子透明质酸或其盐、水解透明质酸或其盐、乙酰化透明质酸或其盐、四氢嘧啶或其衍生物、麦角硫 因、酵母菌/大米发酵产物滤液、氨基丁酸、防腐剂和水构成。各组分的质量比,以及分子量等性质如上文所述。
本发明还提供上述组合物在护肤品或化妆品中的应用。
本发明的功效促进组合物包含特定配比的高分子透明质酸、水解透明质酸、乙酰化透明质酸、四氢嘧啶、麦角硫因、酵母菌/大米发酵产物滤液和氨基丁酸,具有有效的功效促进功能。例如,能够显著的促进补水、提高活性成分的稳定性、提高抗衰老成分的吸收等。这可能是由于一方面乙酰化透明质酸以特定的配比连接特定分子量的高分子透明质酸和水解透明质酸,在三维空间内构建稳定的“工”字形通道,另一方面四氢嘧啶、麦角硫因、酵母菌/大米发酵产物滤液和氨基丁酸四者协同作用,保证透明质酸钠及其衍生物形成的“工”字形结构的高效运行。
实施例
下面结合实施例进一步说明本发明,应当理解,实施例仅用于进一步说明和阐释本发明,并非用于限制本发明。
下述实施例中所使用的实验方法如无特殊要求,均为常规方法。
下述实施例中所使用的材料、试剂等,如无特殊说明,均可从商业途径得到。其中,高分子量透明质酸钠、水解透明质酸钠、乙酰化透明质酸钠、四氢甲基嘧啶羧酸、麦角硫因、酵母菌/大米发酵产物滤液、氨基丁酸均来源于华熙生物科技股份有限公司。
实施例1
将2.5g高分子量透明质酸钠(1200kDa)加入适量水中,搅拌至完全溶解;然后加入2.5g水解透明质酸钠(5kDa)及1g乙酰化透明质酸钠(分子量4kDa,乙酰基含量24%),搅拌均匀至完全溶解;依次加入3g四氢甲基嘧啶羧酸、7g麦角硫因、20g酵母菌/大米发酵产物滤液、1.5g氨基丁酸、5g防腐剂(戊二醇2.5g,己二醇2.5g),补水到100g,搅拌均匀至完全溶解,得功效促进组合物。
实施例2-13、对比例1-8与实施例1的不同之处在于高分子量透明质酸钠、水解透明质酸钠、乙酰化透明质酸钠的分子量或含量、四氢甲基嘧啶羧酸、麦 角硫因、酵母菌/大米发酵产物滤液、氨基丁酸的含量不同,具体如表1所示。其中,实施例9与实施例1的区别仅在于高分子透明质酸钠分子量不同;实施例10与实施例1的区别仅在于高分子透明质酸钠的含量不同;实施例11与实施例1的区别仅在于水解透明质酸钠的含量不同;实施例12与实施例1的区别仅在于水解透明质酸钠的分子量不同;实施例13与实施例1的区别在于乙酰化透明质酸钠的含量不同。
表1各实施例和对比例各组分含量
Figure PCTCN2021075783-appb-000001
注:“-”表示无,即在组合物中制备中不加入
试验例1补水效果
1、测试前臂的22个不同区域(区域编号为1-22)的皮肤含水量,记录初始值数据。
2、在实施例1-13、对比例1-8制备的功效促进组合物中分别添加在组合物中质量百分比为1%的神经酰胺-3,得到实施例1-13和对比例1-8对应的补水组合物。
3、在前臂的21个不同区域(区域编号为1-21)涂抹同等量的实施例1-13、对比例1-8对应的补水组合物,30分钟后使用皮肤水分散失测定仪Tewameter TM300(Courage+Khazaka,德国)测试皮肤含水量并记录。其中,实施例1的补水组合物对应1号区域,实施例2的补水组合物对应2号区域,依次类推实施例8的补水组合物对应8号区域,对比例1的补水组合物对应14号区域,对比例2的补水组合物对应15号区域,对比例8的补水组合物对应21号区域。
4、在22号区域涂抹同等量的补水成分溶液(质量百分比为1%的神经酰胺-3)作为对照,30分钟后,测试皮肤含水量并记录。
5、测试人数10人,含水量取平均值。
上述各补水组合物的补水效果如表2所示。
表2各实施例和对比例的补水效果
  含水量(初始值) 含水量(涂抹后)
区域1 36.71 45.33
区域2 35.42 42.87
区域3 36.34 44.76
区域4 35.89 43.76
区域5 36.03 40.22
区域6 36.07 39.46
区域7 36.12 40.21
区域8 36.08 39.72
区域9 35.94 40.11
区域10 36.00 39.42
区域11 36.02 40.15
区域12 36.04 40.24
区域13 36.07 39.73
区域14 36.11 37.00
区域15 36.01 36.59
区域16 35.98 36.91
区域17 36.00 37.10
区域18 36.01 37.23
区域19 35.99 37.01
区域20 36.02 37.34
区域21 36.03 36.24
区域22 36.07 36.11
结论:由表2可知添加本发明实施例制备的组合物后,补水成分的补水能力显著增加,尤其是实施例1-4得到的组合物的补水效果最佳,这说明本发明的功效促进组合物能有效促进补水。
而对比例1-3由于只含三种透明质酸中的两种,补水效果较差,这可能是由于本发明的三种透明质酸可以在三维空间内构建稳定的“工”字形通道,形成从皮肤表面保湿锁水层到皮肤深层补水层的长效补水保湿通道,有效补充水分,增加皮肤含水量,同时“工”字形通道又可以增加神经酰胺-3的透皮吸收效果,增加神经酰胺-3的利用率,增强补水效果。
对比例4-8的补水效果也较差,其中以对比例8达到的补水效果最差,使用前后皮肤含水量相差只有0.21,这可能是由于四氢嘧啶、麦角硫因、酵母菌/大米发酵产物滤液和氨基丁酸四者协同作用,可以维持皮肤表面高分子透明质酸所形成的膜的稳定性和持久性,从而保证透明质酸钠及其衍生物形成的“工”字形结构的高效运行。
试验例2对活性成分的保护作用
在实施例1-13、对比例1-8制备的功效促进组合物中添加虾青素,使得组合物中虾青素的质量百分比为0.01%,得到含虾青素的组合物,分别对应应用 例1-16。其中实施例1得到的虾青素组合物对应应用例1,实施例2得到的虾青素组合物对应应用例2,依次类推,实施例8得到的虾青素组合物对应应用例8,实施例13得到的虾青素组合物对应应用例13,对比例1得到的虾青素组合物对应应用例14,对比例2得到的虾青素组合物对应应用例15,对比例8得到的虾青素组合物对应应用例21。
取等量应用例1-21的虾青素组合物置于透明容器中于室温下放置2h,期间不断搅拌使其与氧气接触,观察组合物的颜色变化,取组合物适量,用三氯甲烷溶剂稀释成浓度为1μg/mL的溶液,用UV8500紫外分光光度计测定489nm处的吸光度。以同等浓度避光密闭保存的虾青素作为对照,相同条件测定489nm处的吸光度。结果如表3所示。
表3各实施例和对比例对活性成分的保护作用
  吸光度
应用例1 0.6579
应用例2 0.6001
应用例3 0.6388
应用例4 0.6320
应用例5 0.4889
应用例6 0.4521
应用例7 0.4711
应用例8 0.4602
应用例9 0.4800
应用例10 0.4603
应用例11 0.4801
应用例12 0.4833
应用例13 0.4698
应用例14 0.3410
应用例15 0.3908
应用例16 0.3922
应用例17 0.3801
应用例18 0.3856
应用例19 0.3846
应用例20 0.3868
应用例21 0.3602
对照 0.6970
结论:虾青素易被氧化使颜色变淡,颜色越淡说明虾青素被氧化越多,虾青素的功效越差。添加本发明实施例制备的组合物后,虾青素的颜色变淡不明显,尤其以实施例1-4的颜色变化最小,与避光密闭保存的对照相比,吸光度仅降低0.0391-0.0969。但是对比例的虾青素组合物颜色变化较大,吸光度降低0.3以上。这说明本发明7种成分构建的功效促进体系,可以提高大分子功效成分比如虾青素的稳定性,增加虾青素与皮肤的接触时间,从而提高虾青素的利用率。
试验例3对抗衰老成分的促进作用
1.通过Visia拍摄眼角及面部皱纹,记录皮肤年龄数据。
2.在实施例1、对比例1、对比例8分别添加1%的祛皱成分(抗皱复合肽),得到具有抗衰老作用的组合物,分别对应应用例22、23、24。
3.分区域涂抹应用例22、23、24每天两次,持续使用12周,每2周用Visia拍摄,记录皮肤年龄数据。
4.测试人数各10人,皮肤年龄取平均值。
表4皮肤年龄数据
  0周 2周 4周 6周 8周 10周 12周
应用例22 56 56 54 53 52 51 50
应用例23 56 56 56 55 55 54 54
应用例24 56 56 56 56 55 55 55
结论:本发明实施例制备的功效促进组合物可以很好的促进抗衰老成分的功效发挥,从上表可以看出,应用例22的抗衰老成分的功效增加显著,使用一段时间后,皮肤年龄减小了6岁,而应用例23、应用例24使用一段时间后, 皮肤年龄变化较小或几乎没有变化。

Claims (10)

  1. 一种功效促进组合物,其特征在于,所述组合物包括高分子透明质酸或其盐、水解透明质酸或其盐、乙酰化透明质酸或其盐、四氢嘧啶或其衍生物、麦角硫因、酵母菌/大米发酵产物滤液、氨基丁酸。
  2. 根据权利要求1所述的组合物,其特征在于,所述组合物中,所述高分子透明质酸或其盐的质量百分比为1-30%,优选为1-10%,所述水解透明质酸或其盐的质量百分比为2%-50%,优选为2-10%,所述乙酰化透明质酸或其盐的质量百分比为1-10%,优选为1-1.5%,所述四氢嘧啶或其衍生物的的质量百分比为0.1%-10%,优选为0.3-5%,所述麦角硫因的质量百分比为2-20%,优选为3-10%,所述酵母菌/大米发酵产物滤液的质量百分比为10-50%,优选为15-40%,所述氨基丁酸的质量百分比为0.1-5%,优选为0.3-3%。
  3. 根据权利要求1或2所述的组合物,其特征在于,按重量份计,所述高分子透明质酸或其盐为1重量份,所述水解透明质酸或其盐为0.2-2重量份,优选为0.5-1重量份,所述乙酰化透明质酸或其盐为0.05-1.5重量份,优选为0.1-0.5重量份。
  4. 根据权利要求1-3任一项所述的组合物,其特征在于,所述高分子量透明质酸或其盐的分子量为1000-1800kDa,优选为1000-1500kDa。
  5. 根据权利要求1-4任一项所述的组合物,其特征在于,所述水解透明质酸的分子量为1kDa-10kDa,优选为5kDa-10kDa。
  6. 根据权利要求1-5任一项所述的组合物,其特征在于,所述乙酰化透明质酸或其盐的分子量为20kDa-100kDa,乙酰基的质量百分比为20-40%。
  7. 根据权利要求1-6任一项所述的组合物,其特征在于,所述四氢嘧啶或其衍生物选自四氢甲基嘧啶羧酸和羟基四氢甲基嘧啶羧酸中的一种或两种,优选为四氢甲基嘧啶羧酸。
  8. 根据权利要求1-7任一项所述的组合物,其特征在于,所述组合物还包括防腐剂,所述防腐剂在所述组合物中的质量百分比为0.1-5%,所述防腐剂选自戊二醇、己二醇、丁二醇和乙基己基甘油中的一种或两种以上。
  9. 权利要求1-8任一项所述的组合物在护肤品或化妆品中的应用。
  10. 一种护肤品或化妆品,其包含权利要求1-8任一项所述的组合物。
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