WO2022073437A1 - 大麻二酚及其与燕窝提取物的组合在皮肤补水保湿中的应用 - Google Patents

大麻二酚及其与燕窝提取物的组合在皮肤补水保湿中的应用 Download PDF

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WO2022073437A1
WO2022073437A1 PCT/CN2021/121008 CN2021121008W WO2022073437A1 WO 2022073437 A1 WO2022073437 A1 WO 2022073437A1 CN 2021121008 W CN2021121008 W CN 2021121008W WO 2022073437 A1 WO2022073437 A1 WO 2022073437A1
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skin
cannabidiol
bird
composition
nest extract
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PCT/CN2021/121008
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English (en)
French (fr)
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詹华强
白磐竹
吴启韵
董婷霞
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香港科技大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • 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
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • 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
    • 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 relates to skin moisturizing; more particularly, the present invention relates to the application of cannabidiol and its combination with bird's nest extract in skin water retention.
  • the present invention provides a solution to the problems associated with skin dryness and dehydration.
  • CBD cannabidiol
  • AQP3 aquaporin 3
  • FLG2 outer skin glycoprotein Filaggrin-2
  • the present invention provides cannabidiol for hydrating skin cells by increasing the gene expression of Aquaporin 3 (AQP3) and/or skin outer layer glycoprotein Filaggrin-2 (FLG2) in skin cells the use of.
  • AQP3 Aquaporin 3
  • FLG2 skin outer layer glycoprotein Filaggrin-2
  • the present invention provides a composition for moisturizing skin cells, comprising cannabidiol and bird's nest extract.
  • the present invention provides a method of increasing gene expression of aquaporin 3 (AQP3) and/or skin outer layer glycoprotein Filaggrin-2 (FLG2) in skin cells, comprising administering to said skin cells Cannabidiol and/or Bird's Nest Extract.
  • AQP3 aquaporin 3
  • FLG2 skin outer layer glycoprotein Filaggrin-2
  • the present invention provides a method of treating skin comprising topically applying the composition of the second aspect to skin in need thereof.
  • the benefits of the present invention are: in the present invention, by using cannabidiol, or a combination of cannabidiol and bird's nest extract for treating dry and dehydrated skin, AQP3 and AQP3 and The expression of the gene encoding FLG2 solves the problems related to skin dryness and dehydration, thereby realizing the moisturizing effect of skin; in addition, in the present invention, the combination of cannabidiol or cannabidiol and bird's nest extract can also By improving the hydration of the skin, the skin can achieve whitening, high-efficiency moisturizing and moisturizing functions, and it is safe and effective for the skin, and has no obvious irritation.
  • Figure 1 shows the cytotoxicity analysis of different concentrations of cannabidiol (CBD) and 3 mg/mL bird's nest extract on keratinocyte HaCaT cells.
  • CBD cannabidiol
  • Figure 2 shows the cytotoxicity analysis graph of the combination of different concentrations of CBD and 3 mg/mL bird's nest extract on HaCaT cells.
  • Figure 3 shows a graph of RT-PCR results of FLG2 gene expression after HaCaT cells were treated with different concentrations of CBD and 3 mg/mL bird's nest extract alone.
  • Figure 4 shows a graph of RT-PCR results of AQP3 gene expression after HaCaT cells were treated with different concentrations of CBD and 3 mg/mL bird's nest extract alone.
  • Figure 5 shows a graph of RT-PCR results of FLG2 gene expression after HaCaT cells were treated with combinations of CBD and 3 mg/mL bird's nest extract at different concentrations.
  • Figure 6 shows a graph of RT-PCR results of AQP3 gene expression after HaCaT cells were treated with combinations of CBD and 3 mg/mL bird's nest extract at different concentrations.
  • Figure 7 shows the results of 12 volunteers using a cream containing CBD and bird's nest extract to perform a human skin sensitivity test, where the blue line is the application area of the cream.
  • cannabidiol and bird's nest extracts are able to increase the intradermal aquaporin 3 (AQP3) and the outer skin glycoprotein Filaggrin- 2 (FLG2) gene expression, both of which play an extremely important role in controlling the water balance inside and outside the skin cells, but the effect is not as obvious when used alone as it is when used in combination. Therefore, cannabidiol and/or bird's nest extract can be used to solve various skin symptoms caused by dry skin and dehydration, such as dullness, roughness, fine lines, loss of luster and elasticity, pigmentation, etc., and then achieve significant whitening, hydrating and moisturizing effects.
  • AQP3 intradermal aquaporin 3
  • FLG2 outer skin glycoprotein Filaggrin- 2
  • cannabidiol and bird's nest extracts have no proliferative effect on skin stratum corneum cells, and have no obvious stimulating effect on the skin, so they can be used externally as topical skin preparations on the skin to enhance the intercellular water retention capacity and improve the skin tissue. Moisture, for the purpose of restoring skin radiance.
  • AQP3 is the most expressed subtype of aquaporin (also known as aquaporin) in human skin. It is located on the cell membrane and is a transporter that can transport small molecules such as water, glycerol and urea across the membrane. Form "pores" in the cell membrane to mediate the transmembrane transport of small molecules such as water, glycerol and urea in the organism, and to regulate the water balance.
  • AQP3 is able to participate in skin hydration, skin barrier function and wound healing, maintain normal skin shape and function, and is associated with keratinocyte proliferation and migration and even early differentiation, atopic dermatitis, vitiligo, skin tumors, psoriasis related to the pathogenesis of various skin diseases. Down-regulation of AQP3 expression was also found to cause natural aging of skin in non-exposed areas.
  • FLG2 protein is a member of the S100 fusion protein family and is located in the epidermal differentiation complex. FLG2 mRNA and protein are mainly found in keratinized epithelium, especially in the skin. The expression pattern of FLG2 is limited to the upper granular layer and stratum corneum, similar to that of filaggrin, and is structurally closely related to filaggrin. FLG2 protein is involved in epithelial homeostasis, and the encoded protein is required for skin keratinization, and defects in this gene are also closely related to the production of skin diseases. In addition, the FLG2 protein also has the function of protecting the skin barrier.
  • cannabidiol When cannabidiol is applied to dry and dehydrated skin, it is found that it can significantly increase the expression of genes encoding AQP3 and FLG2, and solve various skin symptoms caused by dry and dehydrated skin, such as dullness, roughness, Fine lines, loss of radiance and elasticity, pigmentation and more, resulting in dramatic whitening, hydrating and moisturizing effects. And, when the combination of cannabidiol and bird's nest extract was applied to dry, dehydrated skin, it was found that the two could synergistically increase the expression of the genes encoding AQP3 and FLG2 to achieve the water-retaining function of skin cells, thereby achieving significant whitening. , hydrating and moisturizing effects.
  • cannabidiol itself and its combination with bird’s nest extract have no proliferative effect on skin stratum corneum cells, and no obvious stimulating effect on the skin, so it can be used externally on the skin as a topical skin preparation to enhance the intercellular water retention capacity and The purpose of improving the moisture of skin tissue and restoring skin radiance.
  • the present invention proposes the technical concept of cannabidiol itself and the combination of cannabidiol and bird's nest extract for moisturizing and moisturizing skin cells.
  • the discovery of the gene expression of the aquaporin 3 (AQP3) and the outer layer glycoprotein Filaggrin-2 (FLG2) of the skin can effectively hydrate the skin without any side effects.
  • the technical concept of the present invention is different from the technical concept of the topical skin moisturizing preparations in the prior art that increases the hydration degree of the skin by reducing evaporation for skin moisturizing.
  • the present invention provides cannabidiol for hydrating skin cells by increasing the gene expression of Aquaporin 3 (AQP3) and/or skin outer layer glycoprotein Filaggrin-2 (FLG2) in skin cells the use of.
  • AQP3 Aquaporin 3
  • FLG2 skin outer layer glycoprotein Filaggrin-2
  • Cannabidiol (CBD), the main active ingredient in industrial hemp (hemp), is neither addictive nor neurotoxic.
  • CBD cannabidiol
  • cannabidiol is a powerful antioxidant, and has a series of physiological activities such as blocking breast cancer metastasis, anti-epileptic, anti-spasmodic, anti-rheumatoid arthritis, anti-anxiety, and anti-insomnia. Due to its strong antioxidant activity, antibacterial and anti-inflammatory, anti-acne soothing, anti-aging and repairing effects on damaged cells, it has been used in skin care products to play the role of anti-acne and anti-inflammatory, suitable for acne treatment and prevention. Moreover, as demonstrated in the following examples, cannabidiol can increase the expression of genes encoding AQP3 and FLG2, thereby playing a role in moisturizing skin cells.
  • “Hydrating” refers to providing moisture to skin cells. “Moisturizing” usually means allowing moisture to enter the deep cells of the skin and lock it firmly in the bottom of the skin so that it doesn't escape.
  • moistureturizing may be used interchangeably with the terms “water retention” and “water locking”.
  • the effective concentration of cannabidiol is from 0.0001% to 0.001% by weight.
  • the effective concentration of cannabidiol is 0.0005% by weight.
  • the cannabidiol is further combined with bird's nest extract for hydration and moisturizing of skin cells.
  • Bird's nest is recognized as a natural nutritious food for moisturizing the skin. It has the effects of moisturizing lung dryness, nourishing kidney yin, and replenishing deficiency. It also has super antioxidant capacity, which can whiten skin and lighten pigmentation.
  • the bird's nest extract used in the present invention can be obtained commercially or self-extracted.
  • the bird's nest extract of the present invention can be prepared by stewing the bird's nest in water for 1-3 hours, preferably for 2 hours, and then freeze-drying the stewed product.
  • the bird's nest may be crushed and/or soaked before being simmered in water.
  • the effective concentration of the bird's nest extract is at least 0.01% by weight.
  • the effective concentration of the bird's nest extract is at least 0.3% by weight.
  • the combination of cannabidiol and bird's nest extract hydrates skin cells by increasing skin hydration, increasing skin moisturization, and/or conditioning and moisturizing the skin.
  • the present invention provides a composition for moisturizing skin cells, comprising cannabidiol and bird's nest extract.
  • the composition provides skin hydration and moisturization by synergistically increasing the gene expression of aquaporin 3 (AQP3) and/or skin outer layer glycoprotein Filaggrin-2 (FLG2) in skin cells.
  • AQP3 aquaporin 3
  • FLG2 skin outer layer glycoprotein Filaggrin-2
  • the composition can synergistically increase the transcription level of genes encoded by AQP3 and FLG2, thereby achieving water balance inside and outside skin cells, thereby significantly improving skin hydration, increasing skin moisturization, and/or conditioning and moisturizing skin, In order to achieve better skin whitening, moisturizing and moisturizing effect.
  • the cannabidiol is from 0.0001% to 0.001% by weight of the composition.
  • the cannabidiol is 0.0005% by weight of the composition.
  • the bird's nest extract is included in the composition of the present invention, it is sufficient.
  • the bird's nest extract is at least 0.01% by weight of the composition.
  • the bird's nest extract is at least 0.3% by weight of the composition.
  • the composition may contain only cannabidiol, bird's nest extract and water.
  • the cannabidiol may be 0.0001% to 0.001% by weight of the composition, preferably 0.0005% by weight of the composition;
  • the bird's nest extract may be at least 0.0005% by weight of the composition 0.01% by weight, preferably at least 0.3% by weight of the composition; the balance being water.
  • the cannabidiol may be 0.0005% by weight of the composition; the bird's nest extract may be at least 0.3% by weight of the composition; the balance being water.
  • composition of the present invention can also contain other ingredients, such as dosage forms (liquids, ointments, creams, etc.), uses (medical or Cosmetic use, etc.), application method (spray, smear, etc.) and other factors.
  • the present invention provides a method of increasing gene expression of aquaporin 3 (AQP3) and/or skin outer layer glycoprotein Filaggrin-2 (FLG2) in skin cells, comprising administering to said skin cells Cannabidiol and/or Bird's Nest Extract.
  • AQP3 aquaporin 3
  • FLG2 skin outer layer glycoprotein Filaggrin-2
  • the expression “cannabidiol and/or bird's nest extract” includes three cases of cannabidiol, bird's nest extract, and cannabidiol and bird's nest extract.
  • the expression “skin intracellular aquaporin 3 (AQP3) and/or skin outer layer glycoprotein Filaggrin-2 (FLG2)” has a similar meaning.
  • the effective concentration of cannabidiol is from 0.0001% to 0.001% by weight.
  • the effective concentration of cannabidiol is 0.0005% by weight.
  • the effective concentration of the bird's nest extract is at least 0.01% by weight.
  • the effective concentration of the bird's nest extract is at least 0.3% by weight.
  • the present invention provides a method of treating skin comprising topically applying the composition of the second aspect to skin in need thereof.
  • topical application refers to the application of a composition of the present invention by smearing, spraying, applying, etc., to the skin in need (eg face, neck, hands, arms, legs or the skin of the feet).
  • the composition is applied to skin in need of hydration.
  • the composition is applied to fine lines, dullness, uneven skin tone, dryness, peeling, sagging and/or inelastic skin caused by dehydration, thereby addressing the problems caused by the skin Various skin problems caused by dehydration.
  • the active ingredients of the present invention are formulated in the following manner:
  • Bird's nest extract storage solution weigh 3 g of bird's nest (purchased from Hong Kong Manulife), add 300 mL of water, heat and simmer for 2 hours, and freeze-dry to obtain bird's nest extract. Add 100 mL of water to re-dissolve 3 g of bird's nest extract to prepare a bird's nest extract stock solution with a concentration of 30 mg/mL.
  • the MTT assay was used to detect and analyze cell viability.
  • HaCaT glial cells were cultured in DMEM medium supplemented with 10% FBS (fetal bovine serum), 1% penicillin/streptomycin, respectively. Then, the cultured adherent cells at the bottom of the dish were digested with 0.25% trypsin solution to make a cell suspension and counted. Next, a suspension with a cell concentration of 1 ⁇ 10 4 cells/mL was prepared, inoculated on a 96-well plate, and cultured in a CO 2 incubator (5% CO 2 , 37° C.) for 24 hours.
  • a CO 2 incubator 5% CO 2 , 37° C.
  • cannabidiol stock solution and the bird's nest extract stock solution are then respectively added to obtain the desired concentrations of cannabidiol, bird's nest extract, and the combination of cannabidiol and bird's nest extract.
  • the medium in the 96-well plate was aspirated, 0.5 mg/mL MTT solution was added, and the cells were placed in an incubator for 4 hours. After incubation, DMSO solution was added and shaken on a shaker for 15 minutes, and the absorbance at 570 nm was measured to analyze cell viability. The results are shown in Figures 1 and 2.
  • Figure 1 shows that HaCaT cells were treated with different concentrations (1 ⁇ g/mL, 2.5 ⁇ g/mL, 5 ⁇ g/mL, 10 ⁇ g/mL, and 25 ⁇ g/mL) of cannabidiol and bird’s nest extract (3 mg/mL) alone, respectively. cell viability. Compared with the results of the control, the survival rate of HaCaT cells was improved after the cannabidiol treatment at the concentration of 1 ⁇ g/mL to 5 ⁇ g/mL.
  • Figure 2 shows HaCaT cells treated with different concentrations (1 ⁇ g/mL, 2.5 ⁇ g/mL, 5 ⁇ g/mL, 10 ⁇ g/mL and 25 ⁇ g/mL) of cannabidiol in combination with bird’s nest extract (3 mg/mL), respectively cell viability.
  • concentration of cannabidiol did not exceed 5 ⁇ g/mL, the survival rate of HaCaT cells was improved and showed no cytotoxicity compared to the results of the control.
  • the cell viability was comparable to the control, but when the cannabidiol concentration in the composition was 25 ⁇ g/mL, the viability of the HaCaT cells was significantly decreased (p ⁇ 0.01).
  • Fig. 1 and Fig. 2 show that when the concentration of cannabidiol in the combination of the present invention does not exceed 10 ⁇ g/ml, it does not induce adverse effects on skin cells, and its safety is reliable.
  • the present invention also found that no matter whether the cannabidiol and bird's nest extract were used alone or in combination, compared with the control, there was no effect on the proliferation of HaCaT cells (p>0.05, see Figure 1 and Figure 2) .
  • Example 3 Effects of cannabidiol and/or bird's nest extract on gene expression related to skin hydration
  • HaCaT cells were made into a suspension at a cell concentration of 5 ⁇ 10 5 cells/mL and seeded on a 6-well plate. Put into a CO 2 incubator (5% CO 2 , 37° C.) for 24 hours. Appropriate amounts of the cannabidiol stock solution and the bird's nest extract stock solution are then respectively added to obtain the desired concentrations of cannabidiol, bird's nest extract, and the combination of cannabidiol and bird's nest extract. After a further 24 hours of culture, mRNA was extracted from HaCaT cells and RT-PCR was performed using primers for genes encoding AQP3 and FLG2. The primer sequences are as follows:
  • AQP3F-primer 5'-AGACAGCCCCTTCAGGATTT-3'
  • AQP3R-primer 5'-TCCCTTGCCCTGAATATCTG-3'
  • FLG2F-primer 5'-CTGTGGTCATTCATGGAGTGG-3'
  • FLG2R-primer 5'-CCCTAGAAGGGCTAATGTGTGA-3'
  • Figure 3 shows the expression results of the FLG2-encoding gene obtained by treating HaCaT cells with different concentrations (1 ⁇ g/mL, 2.5 ⁇ g/mL and 5 ⁇ g/mL) of cannabidiol and bird’s nest extract (3 mg/mL) alone, respectively.
  • Figure 4 shows the expression results of AQP3-encoding gene obtained by treating HaCaT cells with different concentrations (1 ⁇ g/mL, 2.5 ⁇ g/mL and 5 ⁇ g/mL) of cannabidiol and bird’s nest extract (3 mg/mL) alone, respectively.
  • treatment of skin cells with cannabidiol alone increased the gene expression of FLG2 and AQP3 by approximately 20% to 40%.
  • Figure 5 shows the expression results of the FLG2-encoding gene obtained by treating HaCaT cells with a combination of cannabidiol and bird's nest extract (3 mg/mL) at different concentrations (1 ⁇ g/mL, 2.5 ⁇ g/mL, and 5 ⁇ g/mL); 6 shows the expression results of AQP3-encoding gene in HaCaT cells treated with different concentrations (1 ⁇ g/mL, 2.5 ⁇ g/mL and 5 ⁇ g/mL) of cannabidiol in combination with bird’s nest extract (3 mg/mL).
  • treatment of HaCaT cells with the combination of different concentrations of cannabidiol and 3 mg/mL bird's nest extract can significantly increase the transcription levels of FLG2 and AQP3 encoding genes.
  • cannabidiol was combined with 3 mg/mL of bird's nest extract at 5 ⁇ g/ml, the enhancement effect on the expression of FLG2 and AQP3 encoding genes was the best, and the improvement rate was about 30% to 80%.
  • cannabidiol and bird's nest extract significantly increased the expression of genes related to skin hydration and moisturization, so it may be the best choice for skin cosmetics.
  • the inventor prepared a cream containing cannabidiol and bird's nest extract, the raw materials of which include the following components by weight :
  • Phase A deionized water 66.6%, carbomer (U20) 0.2%, EDTA-2Na0.1%, methylparaben 0.15%, glycerin 3%, allantoin 0.2%, xanthan gum 0.1%, 1, 3-Butanediol 3%;
  • Phase B Sabic Emulsifier 3%, Triethanolamine 2%, 16/18 Alcohol 1%, Squalane Alcohol 0.5%, Squalane 0.5%, Ethyl Ethyl Palmitate 5%, Caprylic/Capric Triglyceride Ester 4%, isononyl isononanoate 5%, polydimethylsiloxane 2%, tocopheryl acetate 0.5%, hydroxyphenyl ester 0.1%;
  • Phase C Triethanolamine (TEA) 0.25%, water 1%;
  • Phase D essence 2%, purslane 1%, phenoxyethanol 0.5%;
  • Active ingredients cannabidiol 0.0005%, bird's nest extract 0.3%.
  • the preparation steps of the cream include:
  • phase A 1) Sprinkle U20 on the water surface of deionized water, after it is completely wetted, add other ingredients in phase A, stir at about 85°C at 1300rpm for 30min, until completely dissolved, obtain phase A;
  • phase A and phase B continue to stir the mixture of phase A and phase B at 80°C for 10min, then cool down to about 65°C, and carry out vacuum defoaming;
  • Figure 7 shows a graph of the results of a human skin sensitivity test performed by the 12 volunteers using a cream containing cannabidiol (CBD) and bird's nest extract. As shown in FIG. 7 , there was no obvious change in the skin of all volunteers, which indicated that the cream of the present invention was not irritating to the skin, and was a mild and strong moisturizing and moisturizing preparation.
  • CBD cannabidiol
  • Table 1 The moisturizing and moisturizing rate of the cream of the present invention
  • MMV1 skin MMV value before applying cream
  • MMV2 skin MMV value 1 week after applying cream
  • moisturizing rate MMV2/MMV1 ⁇ 100%.
  • the test results of the skin moisturizing and moisturizing performance test table show that the cannabidiol-bird's nest cream of the present invention has been used by twelve volunteers for one week, and the skin moisturizing and moisturizing rate has been significantly improved, and No allergic skin reaction occurred.

Abstract

本发明涉及大麻二酚(CBD)自身以及包含大麻二酚(CBD)和燕窝提取物的组合物对皮肤细胞组织的补水保湿功效。大麻二酚(CBD)以及所述组合物通过提高皮肤细胞内水通道的基因Aquaporin 3(AQP3)和皮肤细胞外层糖蛋白的基因Filaggrin-2(FLG2)的转录水平，能够增强细胞间保水能力和皮肤组织的水分，使皮肤达到深层补水、恢复皮肤光泽效果，且对皮肤角质层细胞无增殖作用，对皮肤无明显的刺激效果，是安全高效的补水保湿剂。

Description

大麻二酚及其与燕窝提取物的组合在皮肤补水保湿中的应用 技术领域
本发明涉及皮肤的补水保湿；更具体地，本发明涉及大麻二酚及其与燕窝提取物的组合在皮肤保水中的应用。
背景技术
现代人生活节奏快、压力大、睡眠差，再加上环境污染日益严重，紫外线、电脑电器辐射、吸烟喝酒、运动不足、食用过多的加工食品与油脂的过度摄取等等，这些因素都会造成许多皮肤问题，如皮肤干燥、脱皮、毛孔粗大、痤疮、暗沉、肤色不均、皮肤松弛等。众所周知，几乎每种肌肤问题都与水分保持和补充有关。水分是美丽肌肤的第一要素，美白、防晒、控油等是在保湿补水的基础上完成。而缺水已成为当代女性肌肤衰老的元凶，当肌肤缺水时，细胞代谢、信息传递等受到影响，皮肤的生理结构发生变化如皮肤干燥、粗糙、失去光泽、弹性减低、皱纹增多或加深、色素增多，最糟糕的是缺水引起的皮肤屏障功能障碍，不但增加皮肤病的易感性，并且可能诱发和加重一些皮肤病，如皮炎、湿疹、银屑病、痤疮等。
现有的局部皮肤用制剂大多通过减少蒸发来增加皮肤的水合度，一般包括天然存在的皮肤脂质、甾醇、以及人造或天然的油等。然而，与这种制剂相关的问题有保湿能力不足、厚重和油腻感、对皮肤的刺激性等。
因此，本领域迫切需要一种能够安全且高效地对皮肤细胞进行补水保湿的解决方案。
发明内容
如上所述，本领域亟需一种能够安全且高效地向皮肤补充水分并保 持皮肤水分、从而使皮肤达到湿润、美白状态的解决方案。由此，本发明提供了与皮肤干燥和缺水有关的问题的解决方案。
本申请的发明人意外地发现，大麻二酚(CBD)能够提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达，从而实现对皮肤细胞的补水保湿。当进一步将大麻二酚(CBD)和燕窝提取物组合使用时，两者能够协同地提高AQP3和FLG2编码基因的表达，从而提高皮肤的水合度、增加皮肤湿润度、增强细胞间保水能力、以及调理并滋润皮肤，进而达到保湿、补水和美白等效果。基于此发现，本发明人完成了本发明。
在第一方面，本发明提供了大麻二酚用于通过提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和/或皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达来实现皮肤细胞补水保湿的用途。
在第二方面，本发明提供了一种用于皮肤细胞补水保湿的组合物，其包含大麻二酚和燕窝提取物。
在第三方面，本发明提供了一种提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和/或皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达的方法，包括向所述皮肤细胞施用大麻二酚和/或燕窝提取物。
在第四方面，本发明提供了一种处理皮肤的方法，其包括对有需要的皮肤局部施用第二方面所述的组合物。
本发明的有益之处在于：在本发明中，通过将大麻二酚、或大麻二酚与燕窝提取物的组合用于处理干燥和缺水的皮肤，可以单独地或协同增效地提高AQP3和FLG2编码基因的表达，从而解决与皮肤干燥和缺水有关的问题，进而实现了皮肤的补水保湿效果；此外，在本发明中，大麻二酚、或大麻二酚与燕窝提取物的组合还能够通过提高皮肤的水合度而使皮肤达到美白、高效补水和保湿功能，并且对皮肤安全、有效，且无明显的刺激性。
附图说明
本发明附图与本发明的实施方案一起提供了对本发明的进一步解释，并且构成说明书的一部分。显而易见地，下面描述中的示例性的附图仅仅涉及本发明的一些实施方案，而并不构成对本发明的限制。对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的实施方案。
图1示出了不同浓度的大麻二酚(CBD)以及3mg/mL的燕窝提取物对角质细胞HaCaT细胞的细胞毒性分析图。
图2示出了不同浓度的CBD与3mg/mL的燕窝提取物的组合对HaCaT细胞的细胞毒性分析图。
图3示出了不同浓度的CBD和3mg/mL的燕窝提取物单独地处理HaCaT细胞后的FLG2基因表达的RT-PCR结果图。
图4示出了不同浓度的CBD和3mg/mL的燕窝提取物单独地处理HaCaT细胞后的AQP3基因表达的RT-PCR结果图。
图5示出了不同浓度的CBD和3mg/mL的燕窝提取物的组合处理HaCaT细胞后的FLG2基因表达的RT-PCR结果图。
图6示出了不同浓度的CBD和3mg/mL的燕窝提取物的组合处理HaCaT细胞后的AQP3基因表达的RT-PCR结果图。
图7示出了12名志愿者使用包含CBD和燕窝提取物的霜剂进行人体皮肤敏感性测试的结果图，其中蓝线部分为霜剂的涂抹区域。
具体实施方式
下面将结合实施例和附图对本发明进行详细的描述。需理解，以下描述仅以示例方式来对本发明进行说明，而无意于对本发明的范围进行限制，本发明的保护范围以随附权利要求为准。并且，本领域技术人员理解，在不背离本发明的精神和主旨的情况下，可以对本发明的技术方案进行修改。若并未特别指明，实施例中所用的技术手段为本领域技术人员所熟知的常规手段。
如上所述，本发明人意外地发现，大麻二酚和燕窝提取物，无论是单独地使用还是组合地使用，都能够提高皮肤内水通道蛋白Aquaporin 3(AQP3)和皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达，这两个基因均对控制皮肤细胞内外的水平衡有着极其重要的作用，但是在单独使用时效果不如组合使用时明显。因此，大麻二酚和/或燕窝提取物可以用于解决由皮肤干燥、缺水带来的各种皮肤症状，如暗沉、粗糙、细纹、失去光泽和弹性、色素沉积等，进而实现显著的美白、补水和保湿效果。并且，大麻二酚和燕窝提取物对皮肤角质层细胞均无增殖作用，对皮肤无明显的刺激效果，因此可以作为局部皮肤用制剂外用在皮肤上，达到增强细胞间保水能力和提高皮肤组织的水分，恢复皮肤光泽的目的。
AQP3是人类皮肤中表达最多的一种水通道蛋白(又被称为水孔蛋白)亚型，其位于细胞膜上，是能够跨膜运输水、甘油和尿素等小分子物质的转运蛋白，其通过在细胞膜上组成“孔道”而介导生物体内的水、甘油和尿素等小分子物质的跨膜转运，并调节水平衡。已经发现，AQP3能够参与皮肤水合、皮肤屏障功能以及创伤愈合，维持皮肤的正常形态和功能，并且与角质形成细胞的增殖和迁移甚至早期分化、特应性皮炎、白癜风、皮肤肿瘤、银屑病等多种皮肤病的发病机制相关。也发现AQP3的表达下调会引起非曝光部位皮肤的自然老化。
FLG2蛋白是S100融合型蛋白家族成员之一，定位于表皮分化复合体中。FLG2 mRNA和蛋白质主要存在于角化上皮中，特别是在皮肤中。FLG2的表达模式仅限于颗粒状上层和角质层，与丝聚蛋白的表达模式相似，结构上也与丝聚蛋白紧密相关。FLG2蛋白参与上皮内稳态，并且该编码蛋白是皮肤角质化所必需的，而该基因的缺陷也与皮肤病的产生息息相关。此外，FLG2蛋白质同样具有保护皮肤屏障的功能。
当将大麻二酚施用于干燥、缺水的皮肤时，发现其能够显著地提高AQP3和FLG2编码基因的表达，解决由皮肤干燥、缺水带来的各种皮肤症状，如暗沉、粗糙、细纹、失去光泽和弹性、色素沉积等，进而实现显著的美白、补水和保湿效果。并且，当将大麻二酚与燕窝提取物的组合施用于干燥、缺水的皮肤时，发现两者能够协同地提高AQP3 和FLG2编码基因的表达，实现皮肤细胞的保水功能，进而实现显著的美白、补水和保湿效果。并且，大麻二酚自身及其与燕窝提取物的组合对皮肤角质层细胞无增殖作用，对皮肤无明显的刺激效果，因此可以作为局部皮肤用制剂外用在皮肤上，达到增强细胞间保水能力和提高皮肤组织的水分，恢复皮肤光泽的目的。
因此，本发明提出了大麻二酚自身、以及大麻二酚与燕窝提取物的组合用于皮肤细胞的补水保湿的技术构思，该技术构思是基于大麻二酚和燕窝提取物均能够提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达的这一发现，由此能够高效地对皮肤进行补水保湿且安全无副作用。本发明的技术构思不同于现有技术的局部皮肤用补水制剂通过减少蒸发来增加皮肤的水合度进行皮肤补水的技术构思。
在第一方面，本发明提供了大麻二酚用于通过提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和/或皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达来实现皮肤细胞补水保湿的用途。
大麻二酚(CBD)是工业大麻(汉麻)中含量较多的主要活性成分，既没有成瘾性，也没有神经毒性。近年来发现大麻二酚为强力的抗氧化剂，并且具有阻断乳腺癌转移、抗癫痫、抗痉挛、抗类风湿性关节炎、抗焦虑、抗失眠等一系列生理活性功能。由于其较强的抗氧化活性、抗菌消炎、祛痘舒缓、延缓衰老和对损伤细胞的修复作用，现已被应用到护肤品中，发挥祛痘、消炎之功效，适合应用于痤疮的治疗及预防。并且，如下文实施例所证实，大麻二酚能够提高AQP3和FLG2编码基因的表达，从而起到对皮肤细胞补水保湿的作用。
“补水”是指向皮肤细胞提供水分。“保湿”通常是指让水分进入到皮肤深层细胞，并且在肌肤底部牢牢地锁住水分，不让水分流失。在本文中，术语“保湿”可以与术语“保水”和“锁水”互换使用。
在一个具体实施方案中，所述大麻二酚的有效浓度为0.0001重量％至0.001重量％。
在一个优选的实施方案中，所述大麻二酚的有效浓度为0.0005重 量％。
在又一个具体实施方案中，所述大麻二酚进一步与燕窝提取物组合用于皮肤细胞补水保湿。
燕窝是公认的滋润皮肤的天然营养食品，有润肺燥、滋肾阴、补虚损的功效，并且具有超强的抗氧化能力，能够美白肌肤，淡化色斑。本发明中使用的燕窝提取物可以是商购获得的，也可以是自行提取的。
在一个具体实施方案中，本发明的燕窝提取物可以通过如下方式制备得到的：将燕窝在水里炖煮1-3小时，优选炖煮2小时，然后对炖煮后的产物进行冷冻干燥。
在一个任选的实施方案中，在将燕窝在水里炖煮之前，可以对燕窝进行粉碎和/或浸泡。
在又一个具体实施方案中，所述燕窝提取物的有效浓度为至少0.01重量％。
在一个优选的实施方案中，所述燕窝提取物的有效浓度为至少0.3重量％。
在又一个具体实施方案中，所述大麻二酚与燕窝提取物的组合通过提高皮肤的水合度、增加皮肤湿润度、和/或调理并滋润皮肤来进行皮肤细胞补水保湿。
在第二方面，本发明提供了一种用于皮肤细胞补水保湿的组合物，其包含大麻二酚和燕窝提取物。所述组合物通过协同地提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和/或皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达来进行皮肤补水保湿。所述组合物能够协同增效地提高AQP3和FLG2编码基因的转录水平，从而实现皮肤细胞内外的水平衡，进而显著地提高皮肤的水合度、增加皮肤湿润度、和/或调理并滋润皮肤，进而实现使皮肤达到更好的美白、补水和保湿效果。
在一个具体实施方案中，所述大麻二酚为所述组合物的0.0001重量％至0.001重量％。
在一个优选实施方案中，所述大麻二酚为所述组合物的0.0005重 量％。
可以理解，只要本发明的组合物中包含燕窝提取物即可。在一个实施方案中，所述燕窝提取物为所述组合物的至少0.01重量％。
在一个优选的实施方案中，所述燕窝提取物为所述组合物的至少0.3重量％。
在一个实施方案中，所述组合物可以仅含有大麻二酚、燕窝提取物和水。在这种情况下，所述大麻二酚可以为所述组合物的0.0001重量％至0.001重量％，优选为所述组合物的0.0005重量％；所述燕窝提取物可以为所述组合物的至少0.01重量％，优选为所述组合物的至少0.3重量％；余量为水。
在一个优选的实施方案中，所述大麻二酚可以为所述组合物的0.0005重量％；所述燕窝提取物可以为所述组合物的至少0.3重量％；余量为水。
当然，本领域技术人员可以理解，除了大麻二酚、燕窝提取物和水以外，本发明的组合物还可以包含其他成分，根据需要例如剂型(液体、膏剂、霜剂等)、用途(医用或美容用等)、施用方式(喷雾、涂抹等)等等因素。
在第三方面，本发明提供了一种提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和/或皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达的方法，包括向所述皮肤细胞施用大麻二酚和/或燕窝提取物。
可以理解，在本文中，表述“大麻二酚和/或燕窝提取物”包括大麻二酚、燕窝提取物、以及大麻二酚和燕窝提取物三种情况。表述“皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和/或皮肤外层糖蛋白Filaggrin-2(FLG2)”具有类似的含义。
在一个具体的实施方案中，所述大麻二酚的有效浓度为0.0001重量％至0.001重量％。
在一个优选的实施方案中，所述大麻二酚的有效浓度为0.0005重量％。
在一个具体的实施方案中，所述燕窝提取物的有效浓度为至少0.01重量％。
在一个优选的实施方案中，所述燕窝提取物的有效浓度为至少0.3重量％。
在第四方面，本发明提供了一种处理皮肤的方法，其包括对有需要的皮肤局部施用第二方面所述的组合物。
在本发明的上下文中，“局部施用”是指通过涂抹、喷涂、敷用等方式施用本发明的组合物到有需要的皮肤(例如脸部、颈部、手部、臂部、腿部或脚部的皮肤)的表面上。
在一个具体的实施方案中，将所述组合物施用于需要补水保湿的皮肤。
在一个进一步具体的实施方案中，将所述组合物施用于由缺水导致的有细纹、暗沉、肤色不均、干燥、脱皮、松弛和/或无弹性的皮肤，由此解决由皮肤缺水带来的各种皮肤问题。
以下实施例将使本领域技术人员进一步了解本发明的技术方案和益处，但并不旨在限制本发明。
实施例
实施例1：燕窝提取物和大麻二酚(CBD)配制
本发明的活性成分按照以下方式进行配制：
燕窝提取物储液：称量3g燕窝(购于香港宏利行)，加入300mL水，加热炖煮2小时后，进行冷冻干燥得到燕窝提取物。在3g燕窝提取物中加入100mL水重新溶解，制备浓度为30mg/mL的燕窝提取物储液。
大麻二酚(CBD，购于云南汉素生物科技有限公司)储液：称取10mg大麻二酚，加入少量DMSO，搅拌直至大麻二酚完全溶解，然后补水至100mL，从而制备获得浓度为100μg/mL的大麻二酚储液。
实施例2：细胞毒性分析
为评估本发明的组合物在角质细胞中是否具有细胞毒性，以及是否会刺激皮肤细胞增生，使用MTT法进行检测，并分析细胞存活率。HaCaT胶质细胞分别在补充有10％FBS(胎牛血清)、1％青霉素/链霉素的DMEM培养基中进行培养。然后，用0.25％胰蛋白酶溶液消化培养皿底部经培养的贴壁细胞，制成细胞悬浮液，并对其计数。接着制成细胞浓度为1×10 4个/mL的悬浮液并接种在96孔板上，放入CO 2培养箱(5％CO 2、37℃)中培养24小时。然后分别加入适量的大麻二酚储液、燕窝提取物储液，以获得所需浓度的大麻二酚、燕窝提取物、以及大麻二酚与燕窝提取物的组合。继续培养24小时后，吸去96孔板中的培养基，加入0.5mg/mL的MTT溶液，放入培养箱中培养4小时。培育完毕，加入DMSO溶液并在摇床上振摇15分钟，测量570nm处的吸光度，进而分析细胞的生存活力。结果如图1和图2所示。
图1示出了分别由不同浓度(1μg/mL、2.5μg/mL、5μg/mL、10μg/mL和25μg/mL)的大麻二酚、以及燕窝提取物(3mg/mL)单独处理HaCaT细胞的细胞存活率。相比对照的结果可知，经浓度为1μg/mL至5μg/mL的大麻二酚处理后的HaCaT细胞的存活率提高。而当组合物中大麻二酚浓度为10μg/mL时，HaCaT细胞的存活率与对照相当，但是当组合物中大麻二酚浓度为25μg/mL时，HaCaT细胞的存活率相比对照显著降低，显示出明显的细胞毒性(p＜0.05)。
图2示出了分别由不同浓度(1μg/mL、2.5μg/mL、5μg/mL、10μg/mL和25μg/mL)的大麻二酚与燕窝提取物(3mg/mL)的组合处理的HaCaT细胞的细胞存活率。同样地，相比对照的结果可知，当大麻二酚的浓度不超过5μg/mL时，HaCaT细胞的存活率提高，没有显示出细胞毒性。当大麻二酚为10μg/mL时，细胞存活率与对照相比相当，但是当组合物中大麻二酚浓度为25μg/mL时，HaCaT细胞的存活率明显下降(p＜0.01)。
图1和图2的试验结果表明，当本发明的组合中大麻二酚的浓度 不超过10μg/ml时，不会诱发皮肤细胞产生不利影响，其安全性是可靠的。
另外，本发明还发现，无论是大麻二酚和燕窝提取物单独地使用还是组合地使用，与对照相比，均未见对HaCaT细胞增生有作用(p＞0.05，参见图1和图2)。
实施例3：大麻二酚和/或燕窝提取物对与皮肤补水保湿相关的基因表达的影响
为了进一步确认大麻二酚和/或燕窝提取物对皮肤的补水保湿功效，使用RT-PCR测量了皮肤细胞的AQP3和FLG2编码基因的转录水平。
首先，将HaCaT细胞制成细胞浓度为5×10 5个/mL的悬浮液并接种在6孔板上。放入CO 2培养箱(5％CO 2、37℃)中培养24小时。然后分别加入适量的大麻二酚储液、燕窝提取物储液，以获得所需浓度的大麻二酚、燕窝提取物、以及大麻二酚与燕窝提取物的组合。继续培养24小时后，从HaCaT细胞中提取mRNA并使用用于AQP3和FLG2编码基因的引物进行RT-PCR。引物序列如下：
AQP3F-引物：5’-AGACAGCCCCTTCAGGATTT-3’
AQP3R-引物：5’-TCCCTTGCCCTGAATATCTG-3’
FLG2F-引物：5’-CTGTGGTCATTCATGGAGTGG-3’
FLG2R-引物：5’-CCCTAGAAGGGCTAATGTGTGA-3’
图3示出了分别用不同浓度(1μg/mL、2.5μg/mL和5μg/mL)的大麻二酚和燕窝提取物(3mg/mL)单独处理HaCaT细胞得到的FLG2编码基因的表达结果。图4示出了分别用不同浓度(1μg/mL、2.5μg/mL和5μg/mL)的大麻二酚和燕窝提取物(3mg/mL)单独处理HaCaT细胞得到的AQP3编码基因的表达结果。如图3和图4所示，单独用大麻二酚处理皮肤细胞，使FLG2和AQP3的基因表达提升了约20％至40％。特别地，当大麻二酚浓度为2.5μg/ml时，对FLG2的基因表达效 果最好；当大麻二酚浓度为5μg/ml时，对AQP3的基因表达功效最好。单独用燕窝提取物处理HaCaT细胞，FLG2和AQP3编码基因转录水平的提高约为10％至20％。
这些结果表明：单独用大麻二酚或者燕窝提取物对皮肤进行处理有补水保湿之功效。
图5示出了用不同浓度(1μg/mL、2.5μg/mL和5μg/mL)的大麻二酚与燕窝提取物(3mg/mL)的组合处理HaCaT细胞得到的FLG2编码基因的表达结果；图6示出了用不同浓度(1μg/mL、2.5μg/mL和5μg/mL)的大麻二酚与燕窝提取物(3mg/mL)的组合处理HaCaT细胞得到的AQP3编码基因的表达结果。如图5和图6所示，用不同浓度的大麻二酚与3mg/mL的燕窝提取物的组合对HaCaT细胞进行处理，均可以显著提高FLG2和AQP3编码基因的转录水平。并且，当大麻二酚以5μg/ml与3mg/mL的燕窝提取物组合时，对FLG2和AQP3编码基因表达的提升效果最好，提高率约为30％至80％。
由此可知，大麻二酚与燕窝提取物的组合更显著地提升了皮肤补水保湿相关基因的表达，因此可能是应用到皮肤化妆品的最佳选择。
实施例4：大麻二酚-燕窝霜剂的制备
为了进一步测试大麻二酚与燕窝提取物的组合局部皮肤施用的安全性和补水保湿性能，发明人制备了一种含有大麻二酚及燕窝提取物的霜剂，其原料按重量份计包括如下成分：
A相：去离子水66.6％、卡波姆(U20)0.2％、EDTA-2Na0.1％、羟苯甲脂0.15％、甘油3％、尿囊素0.2％、黄原胶0.1％、1，3-丁二醇3％；
B相：赛比克乳化剂3％、三乙醇胺2％、16/18醇1％、鲨肝醇0.5％、角鲨烷0.5％、棕榈酸乙基乙酯5％、辛酸/癸酸甘油三酯4％、异壬酸异壬酯5％、聚二甲基硅氧烷2％、生育酚乙酸酯0.5％、羟苯基酯0.1％；
C相：三乙醇胺(TEA)0.25％、水1％；
D相：香精2％、马齿苋1％、苯氧乙醇0.5％；
活性成分：大麻二酚0.0005％、燕窝提取物0.3％。
所述霜剂的制备步骤包括：
1)将U20洒在去离子水的水面上，待完全润湿后，加入A相中的其他成分，于85℃左右以1300rpm搅拌30min，直至完全溶解，得到A相；
2)将B相中的所有成分混合加热至80℃，保持20min，然后加入A相中，搅拌两分钟以进行均质化；
3)继续在80℃下搅拌A相和B相的混合物持续10min，然后降温至65℃左右，进行真空消泡；
4)在60℃左右加入C相；
5)在45℃左右加入D相；
6)最后加入大麻二酚和燕窝提取物，搅拌均匀后，降至室温即可。
实施例5：皮肤敏感性测试
选取12名志愿者(6男6女，且小臂皮肤健康)，在恒温(24±1℃)、恒湿(50±5％)的房间适应30分钟后用相机拍摄照片，测试受试区域皮肤即左小臂(测试组)和右小臂(对照组)。首先，将实施例4中制备好的大麻二酚-燕窝霜剂分别涂抹在志愿者的左小臂受试区域皮肤，等待1小时后，拍摄照片，同时比较左小臂和右小臂以观察受试区域皮肤有无明显变化，例如红肿、痒、过敏反应等，之后每隔一天再进行相同测试并观察及拍摄照片。
图7示出了该12名志愿者使用包含大麻二酚(CBD)和燕窝提取物的霜剂进行人体皮肤敏感性测试的结果图。如图7所示，所有志愿者的皮肤均未出现明显变化，这表明本发明的霜剂对皮肤无刺激性，是温和且具有较强的补水保湿用制剂。
实施例6：补水保湿性能测试
选取12名志愿者(6男6女，且小臂皮肤健康)，首先，在恒温(24±1℃)、恒湿(50±5％)的房间适应30分钟后，用
Figure PCTCN2021121008-appb-000001
皮肤水分测量仪对12名志愿者的左小臂皮肤的水分含量进行测试，其结果用湿度测量值(Moisture Measurement Value，MMV)来表示，此时的湿度测量值表示为MMV1，即涂抹霜剂前的皮肤MMV值。然后，将实施例4中制备的大麻二酚-燕窝霜剂涂抹在志愿者的左小臂受试区域皮肤，一天三次，一周后再次进行皮肤测试，得到湿度测量值MMV2。比较MMV1和MMV2以评价本发明的霜剂的补水保湿性能。测试结果见下表1。
表1：本发明的霜剂的补水保湿率
Figure PCTCN2021121008-appb-000002
其中：MMV1：涂抹霜剂前的皮肤MMV值；MMV2：涂抹霜剂后1周皮肤MMV值；补水保湿率＝MMV2/MMV1×100％。
如表1所示，皮肤补水保湿性能测试表的测试结果表明，本发明的大麻二酚-燕窝霜剂在十二名志愿者使用一周后，其皮肤补水保湿率都得到了显著的提升，并且均未出现皮肤过敏反应。

Claims (14)

  1. 大麻二酚用于通过提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和/或皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达来实现皮肤细胞补水保湿的用途。
  2. 根据权利要求1所述的用途，其中，所述大麻二酚的有效浓度为0.0001重量％至0.001重量％，优选为0.0005重量％。
  3. 根据权利要求1或2所述的用途，其中，所述大麻二酚进一步与燕窝提取物组合用于皮肤细胞补水保湿。
  4. 根据权利要求1-3中任一项所述的用途，其中，所述燕窝提取物的有效浓度为至少0.01重量％，优选为至少0.3重量％。
  5. 根据权利要求1-4中任一项所述的用途，其中，所述大麻二酚、或大麻二酚与燕窝提取物的组合通过提高皮肤的水合度、增加皮肤湿润度、和/或调理并滋润皮肤来进行皮肤细胞补水保湿。
  6. 一种用于皮肤细胞补水保湿的组合物，其包含大麻二酚和燕窝提取物。
  7. 根据权利要求6所述的组合物，其中，所述大麻二酚为所述组合物的0.0001重量％至0.001重量％，优选为所述组合物的0.0005重量％。
  8. 根据权利要求6-7中任一项所述的组合物，其中，所述燕窝提取物为所述组合物的至少0.01重量％，优选为所述组合物的至少0.3重量％。
  9. 一种提高皮肤细胞内水通道蛋白Aquaporin 3(AQP3)和/或皮肤外层糖蛋白Filaggrin-2(FLG2)的基因表达的方法，包括向所述皮肤细胞施用大麻二酚和/或燕窝提取物。
  10. 根据权利要求9所述的方法，其中，所述大麻二酚的有效浓度为0.0001重量％至0.001重量％，优选为0.0005重量％。
  11. 根据权利要求9或10所述的方法，其中，所述燕窝提取物的有效浓度为至少0.01重量％，优选为至少0.3重量％。
  12. 一种处理皮肤的方法，其包括对有需要的皮肤局部施用权利要求6-8中任一项所述的组合物。
  13. 根据权利要求12所述的方法，其中，将所述组合物施用于需要补水保湿的皮肤。
  14. 根据权利要求12或13所述的方法，其中，将所述组合物施用于由缺水导致的有细纹、暗沉、肤色不均、干燥、脱皮、松弛和/或无弹性的皮肤。
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