KR20230046266A - Cosmetic composition for homeostasis of skin barrier - Google Patents

Abstract

The present invention relates to a cosmetic composition for maintaining homeostasis of skin barrier comprising cannabidiol as an active ingredient, and specifically, provides a composition that is effective in maintaining the homeostasis of the skin barrier by quickly restoring damaged skin barrier by including the cannabidiol as the active ingredient.

Description

Cosmetic composition for maintaining skin barrier homeostasis {Cosmetic composition for homeostasis of skin barrier}

The present invention relates to a cosmetic composition for maintaining skin barrier homeostasis comprising cannabidiol as an active ingredient.

The skin barrier is a physical, chemical, or biological barrier formed by the skin to prevent invasion of pathogens and chemical or physical damage while preventing loss of moisture, minerals, etc., and is a topic of interest in various industries including the cosmetic industry. .

The skin barrier is a concept that includes not only the function as a primary physical barrier, but also an active barrier that means the skin's ability to adapt to the environment, and it can be said to be a concept that comprehensively shows the core skin functions for healthy skin. there is.

Due to the importance of the skin barrier, a number of products for skin barrier improvement have already been released in the existing market, but the existing active ingredients are mainly composed of ingredients that physically seal the barrier, such as ceramide, which provides antioxidant and antibacterial properties. There is a lack of products for active skin barrier improvement in the biochemical part of the back.

In addition, since the main ingredients of most products are concentrated on materials based on pharmaceutical technology, there are many restrictions to apply to natural and organic products, which are increasing consumer demand in the recent cosmetics market, to meet the increasing consumer demand. It also has a difficult problem.

In order to solve these problems, it is necessary to discover effective ingredients for improving the skin barrier that are derived from natural products and can effectively improve not only the physical barrier but also the biochemical skin barrier, and include such effective ingredients to improve the skin barrier function. Development of suitable compositions that can improve is required.

On the other hand, cannabidiol is recognized as a new natural-derived effective ingredient mainly in the North American market, but there are existing regulations on the research and use of cannabidiol, so discussions on the skin efficacy and applicability related to it have been sufficiently discussed. couldn't support

However, as regulatory barriers to cannabidiol have disappeared, the need for research on the various effects of cannabidiol has emerged.

Accordingly, while continuing research on the efficacy of cannabidiol, the present inventors confirmed that cannabidiol has an excellent effect in maintaining homeostasis of the skin barrier by restoring the damaged skin barrier and completed the present invention.

An object of the present invention is to provide an excellent cosmetic composition for maintaining skin barrier homeostasis, particularly for restoring a damaged skin barrier.

In addition, an object of the present invention is to provide a cosmetic composition excellent in improving the recovery rate of the skin barrier.

In order to achieve the above object, the present invention provides a cosmetic composition for maintaining skin barrier homeostasis comprising cannabidiol as an active ingredient.

The present invention also provides a cosmetic composition for improving the recovery rate of the skin barrier, comprising cannabidiol as an active ingredient.

Hereinafter, the present invention will be described in detail.

In the present invention, “cannabidiol” is also referred to as CBD, and is represented by Formula 1 below, 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl] -5-pentyl-1,3-benzenediol or its derivatives, solvates, metabolites (eg skin metabolites), or metabolic precursors.

[Formula 1]

In the present invention, the positive effect of cannabidiol on the skin barrier was verified. First, it was confirmed that cannabidiol promotes the expression of genes that positively affect the skin barrier function by analyzing the overall genome expression pattern of skin cells treated with cannabidiol. In addition, by applying a formulation containing cannabidiol to the skin and measuring the amount of transepidermal water loss compared to formulations without the ingredient, a high recovery rate of the skin barrier and an immediate skin soothing effect were confirmed, which is effective in maintaining the homeostasis of the skin barrier. It was confirmed that there is

In the present invention, the "skin barrier" is a barrier formed by the skin to prevent the intrusion of external substances such as pathogens and the outflow of substances to the outside, as well as to prevent chemical and physical damage and damage such as moisture and minerals. Means a physical, chemical, or physiological barrier.

In the present invention, “maintaining homeostasis of the skin barrier” may mean maintaining the skin barrier in a normal state by restoring it to the skin barrier before damage when the skin barrier is damaged. In particular, it can be applied not only to the physical barrier of the skin but also to the chemical and physiological barriers.

Maintaining the homeostasis of the skin barrier of the present invention may mean restoring a damaged skin barrier.

In the present invention, "recovery of a damaged skin barrier" may mean restoring the skin barrier function after the skin barrier is damaged due to various causes, and specifically may mean speeding up the recovery of the skin barrier function. there is.

In the present invention, "improving the recovery rate of the skin barrier", it takes time for the damaged skin barrier to recover to a normal skin barrier, may mean faster recovery at this time.

In the present invention, the cause of damaging the skin barrier is not particularly limited, but the skin barrier damage may be caused by skin irritation, and the skin irritation may be a concept including both physical and chemical stimulation.

The physical stimulation may include electrical stimulation, mechanical stimulation such as friction, impact, and force, thermal stimulation, stimulation by light such as ultraviolet irradiation, and the like, and chemical stimulation may include acids, bases, surfactants, toxic substances, and viral infections. , but may include stimulation by fine dust, etc., but is not limited thereto.

The composition according to the present invention is intended to restore an already damaged skin barrier, and may be applied to skin with a damaged skin barrier.

In the present invention, cannabidiol may be extracted from hemp seed oil. The extraction method of hemp seed oil is not particularly limited as long as it is a conventional extraction method known in the art.

In the present invention, the cannabidiol may be included in an amount of 0.00001% by weight or more and 10% by weight or less based on the total weight of the cosmetic composition, but is not limited thereto. Preferably, cannabidiol may be included in an amount of 0.00005 wt% or more and 8 wt% or less, and more preferably, cannabidiol may be included in an amount of 0.0001 wt% or more and 5 wt% or less.

When cannabidiol is contained in an amount less than the above range, the effect of cannabidiol is insignificant, and when it is contained in excess, skin trouble, skin irritation, or redness may occur due to excessive cannabidiol.

In the present invention, the cosmetic composition containing cannabidiol can restore the skin barrier by rapidly regulating the homeostasis of the skin barrier by promoting the expression level of genes that positively affect the maintenance of the skin barrier homeostasis.

Specifically, the cosmetic composition containing cannabidiol is MT1H (metallothionein 1H), CYP1A1 (cytochrome P450, family 1, subfamily A, polypeptide 1), TNFRSF10D (tumor necrosis factor receptor superfamily, member 10d), and ALDH3a1 (aldehyde dehydrogenase) Expression of one or more genes selected from 3 family members A1) can be promoted.

In the cosmetic composition of the present invention, components used in conventional skin cosmetics, for example, oil components, aqueous components, surfactants, moisturizers, lower alcohols, thickeners, chelating agents, pigments, preservatives, fragrances, etc. can be appropriately blended as needed. can

The cosmetic composition of the present invention is a solution, external ointment, cream, soothing gel, foam, nutrient lotion, softening lotion, pack, softening water, body wash, emulsion, makeup base, essence, soap, liquid cleanser, bath additive, sunscreen cream, sunscreen It may be prepared in a formulation selected from the group consisting of oil, suspension, emulsion, paste, gel, lotion, powder, soap, foam cleansing, oil, powder foundation, emulsion foundation, wax foundation, patch and spray, but is limited thereto. it is not going to be

In the present invention, the administration route and method of the composition are not particularly limited, but may be preferably transdermal or external skin.

The present invention also provides a quasi-drug composition for maintaining skin barrier homeostasis comprising cannabidiol as an active ingredient.

The present invention also provides a quasi-drug composition for improving the recovery rate of the skin barrier containing cannabidiol as an active ingredient.

Here, cannabidiol, the effect of maintaining the homeostasis of the skin barrier, and the effect of improving the recovery rate of the skin barrier are as described above in the cosmetic composition.

In the present invention, “quasi-drug composition” refers to items that are less active than pharmaceuticals among items used for the purpose of diagnosing, treating, improving, mitigating, treating or preventing human or animal diseases. For example, according to the Pharmaceutical Affairs Act, quasi-drugs This includes products used for the treatment or prevention of diseases in humans and animals, and products with mild or no direct action on the human body, except for products used for medicinal purposes.

In the present invention, the quasi-drug composition includes an organic solvent, a solubilizer, a thickening agent, a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic or nonionic emulsifier, and a filler. , sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, oils, dyes, pigments, fatty substances, hydrophilic or lipophilic actives, dermatology such as any other ingredient commonly used in external preparations for the skin, etc. Adjuvants commonly used in the field may be suitably formulated as needed.

When the composition of the present invention is provided in a formulation for external application to the skin, it may have a formulation such as, but not limited to, an ointment, patch, gel, cream or spray.

The present invention can also provide a use of cannabidiol for maintaining the homeostasis of the skin barrier.

The present invention can also provide the use of cannabidiol to improve the recovery rate of the skin barrier.

The present invention may also provide a method of maintaining skin barrier homeostasis comprising administering cannabidiol to the skin of a subject.

The present invention may also provide a method of improving the rate of recovery of the skin barrier comprising administering cannabidiol to the skin of a subject.

The composition according to the present invention contains cannabidiol as an active ingredient, thereby rapidly recovering the skin barrier damaged by various causes, thereby exhibiting the effect of maintaining the homeostasis of the skin barrier.

Hereinafter, the present invention will be described in detail by the following experimental examples. However, the following experimental examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following experimental examples. In addition, since these experimental examples are only for the purpose of helping the understanding of the present invention, the scope of the present invention is not limited thereto in any sense.

Example

Experimental Example 1. Skin Homeostasis Maintenance Gene Expression Test

In order to confirm the efficacy of cannabidiol in maintaining skin homeostasis through activation of intracellular homeostasis regulating genes, cDNA array gene expression studies were performed using cannabidiol.

1. Materials and Methods

1) Biological model

- cell type: normal human epidermal keratinocytes (NHEK); Using Bioalternatives reference K341 3rd passage

- Culture conditions: 37℃ temperature, 5% CO ₂

-Culture medium: Keratinocyte-SFM medium containing 0.25 ng/ml of epidermal growth factor (EGF), 25 μg/ml of pituitary gland extract (PE), and 25 μg/ml of gentamicin

-Medium for assay: keratinocyte-SFM medium containing 25 μg/ml of gentamicin

2) Test substance

- A cannabidiol solution diluted in ethanol (Sigma 90899; 10mg/ml stock) was prepared.

3) Preliminary cytotoxicity assay

- Cell/compound treatment time: 24 hours

- Evaluation parameters: WST-8 reduction assay and morphology observation using microscopy

2. Cell culture and processing

At the time of cell culture and cannabidiol treatment, the cell culture conditions were divided into three types as follows.

The basic culture condition is that no other external factors are added, the UV treatment condition is UV irradiation during cell culture, and the Poly I:C treatment condition is treatment with (polyinosinic-polycytidylic acid).

1) Basic culture conditions

Normal human epidermal keratinocyte (NHEK) cells were cultured in a 24-well plate in a culture medium for 24 hours, and then further cultured in an assay medium for another 24 hours.

Thereafter, a cannabidiol solution as a test substance was added to each well of the assay medium at 1 ug/ml, and each cell was cultured at 37° C. for 48 hours under 5% CO ₂ . NHEK cells cultured in this way were used as a test group under basic culture conditions.

In addition, NHEK cells cultured in the same manner as the test group except that the cannabidiol solution was not treated were used as a control group.

2) UV treatment conditions

Normal human epidermal keratinocyte (NHEK) cells were cultured in a medium 24-well plate for 24 hours, and then further cultured in an assay medium for another 24 hours.

Thereafter, a cannabidiol solution as a test substance was added to each well of the assay medium at 1 ug/ml, and the cells were cultured for 24 hours at 37°C under 5% CO ₂ .

After 24 hours, all of the cell medium was replaced with medium for assay, and ultraviolet light was irradiated. (UVB 275mJ/cm ² + UVA 1.99J/cm ² ; SOL500 Sun Stimulator with H2 filter, Dr. Honle) Afterwards, the assay medium containing cannabidiol was again treated with the cells and cultured for an additional 24 hours. NHEK cells cultured in this way were used as a test group under UV treatment conditions.

In addition, UV was irradiated in the same manner as in the test group, but NHEK cells cultured without a cannabidiol solution treatment before and after UV irradiation were used as a control group.

3) Poly I:C processing conditions

Normal human epidermal keratinocyte (NHEK) cells were cultured in a medium 24-well plate for 24 hours, and then further cultured in an assay medium for another 24 hours.

Thereafter, a cannabidiol solution as a test substance was added to each well of the assay medium at 1 ug/ml, and the cells were cultured for 24 hours at 37°C under 5% CO ₂ . After 24 hours, the cells were further cultured for 24 hours in an assay medium containing 1 ug/ml of Poly(I:C). NHEK cells cultured in this way were used as a test group for Poly I:C treatment conditions.

In addition, although treated with Poly I:C in the same manner as the test group, NHEK cells cultured without treatment with cannabidiol solution were used as a control group.

n=3 for each condition (both test and control). At the end of culture, cells were washed with PBS solution and immediately frozen at -80 °C.

3. Transcript analysis by DNA array chip

mRNA of each culture cultured according to the above conditions was extracted using TriPure Isolation Solution. Then, the amount of total RNA was quantified using capillary electrophoresis (Bioanalyzer 2100, Agilent technologies). For each extracted RNA, labeled anti-sense RNA (aRNA) was obtained using the GeneChip 3' IVT PLUS kit (Affymetrix®). It was performed for 20 hours at 45 ° C. All experiments and standardization procedures were performed according to the supplier's guidelines The U219 chip after the reaction was measured for fluorescence intensity using the GeneAtlas™ imaging station, and whole transcriptome analysis was performed.

For each condition, the expression level of genes related to skin homeostasis (Table 1) was confirmed through the fold change value, which is the ratio of the expression level of the control group not treated with cannabidiol to that of the test group treated with cannabidiol. Specifically, it is as follows.

gene function MT1H,
Regulates the amount of zinc, a key factor in skin barrier homeostasis, involved in the process of skin cell proliferation (see J Immunol Res. 2018 Dec 9;2018:5404093. doi: 10.1155/2018/5404093) Controls the homeostasis of toxic heavy metal ions in skin cells CYP1A1 Involved in xenobiotic metabolism and regulating Redox homeostasis TNFRSF10D Modulation of thioredoxin function ALDH3a1 It inhibits the oxidation reaction of lipids caused by external UV rays and is involved in the production of lipid peroxides that are harmful to the skin.

1) Basic culture conditions

In the basic culture conditions, gene expression levels were measured for the genes of MT1H, CYP1A1, and TNFRSF10D, and their Fold Change values are shown in Table 2 below. All of these genes correspond to genes that regulate or maintain homeostasis of the skin barrier.

gene Fold Change MT1H 20.7 CYP1A1 12.8 TNFRSF10D 3.4

As shown in Table 2, in the basal culture conditions, it can be confirmed that the test group treated with cannabidiol increased the expression level of genes that control the homeostasis of the skin barrier and proliferate skin cells compared to the control group not treated with cannabidiol. there is.

2) UV treatment conditions

Under UV treatment conditions, gene expression levels were measured for MT1H and ALDH3a1 genes, and their fold change values are shown in Table 3 below.

gene Fold Change MT1H 12.08 ALDH3a1 3.13

As shown in Table 3, it can be seen that the expression levels of MT1H and ALDH3a1 genes, which are genes for regulating skin homeostasis, increased in the test group treated with cannabidiol compared to the control group not treated with cannabidiol under the UV treatment condition. there is.

UV rays are a representative external factor that causes damage to the skin barrier. When cannabidiol is treated on skin damaged by UV rays, it inhibits the oxidation reaction of lipids induced by UV rays and promotes skin cell survival and proliferation, thereby rapidly breaking down the skin barrier. It can restore and maintain skin homeostasis.

3) Poly I:C processing conditions

The gene expression level was measured for the gene of MT1H under Poly (I:C) treatment conditions, and its fold change values are shown in Table 4 below.

gene Fold Change MT1H 4.78

As shown in Table 4, in the Poly (I:C) treatment condition, the expression level of the MT1H gene, a gene for regulating skin homeostasis, increased in the test group treated with cannabidiol compared to the control group not treated with cannabidiol. .

Poly (I:C) treatment conditions simulate damage to the skin barrier caused by internal factors such as viral infection. It can quickly restore the barrier and maintain skin homeostasis.

Experimental Example 2. Evaluation of maintaining skin homeostasis against chemical stimuli

To evaluate the recovery rate of the skin barrier damaged by chemical stimulation, 23 female subjects with an average age of 52.1 years were measured for transepidermal water loss at application sites of cannabidiol-containing and cannabidiol-free products.

Specifically, a product containing 1.3 ppm of cannabidiol and a product having the same other composition but not containing cannabidiol were prepared. Skin irritation was induced for 24 hours by soaking the patch in an aqueous solution containing 2% of sodium lauryl sulfate (SLS), a surfactant that causes skin irritation, and then attaching the patch to both forearm test sites of the subject. After that, a cannabidiol-containing product and a product without cannabidiol were applied to each test site once each morning and evening. It was measured using a video microscope, and the results are shown in Table 5.

Areas where cannabidiol-containing products are applied Areas where cannabidiol-free products are applied before use
(After SLS stimulation) after 1 week of use After 2 weeks of use before use
(After SLS stimulation) 1 week later 2 weeks later average 31.53 15.64 10.73 31.04 20.43 15.68 standard deviation (n=23) 10.33 4.27 2.87 11.04 5.27 4.19

Based on the amount of transepidermal water loss shown in Table 5, the rate of improvement in transepidermal water loss at the application site of the cannabidiol-containing product and the cannabidiol-free product was calculated according to Equation 1 below, and the results are shown in Table 5 below.

[Equation 1]

Improvement rate (%)= |measured value after use-measured value before use (after SLS stimulation)| / Measurement value before use ((after SLS stimulation) × 100

Areas where cannabidiol-containing products are applied Areas where cannabidiol-free products are applied after 1 week of use After 2 weeks of use after 1 week of use After 2 weeks of use Improvement rate (%) 50.39 65.95 34.19 49.50

As shown in Table 6, when a cannabidiol-containing product was applied after SLS stimulation, transepidermal water loss was reduced by 50.39% after 1 week and 65.95% after 2 weeks of use, compared to before use of the product. When the cannabidiol-free product was applied, the amount of transepidermal water loss was reduced by 34.19% after using the product for 1 week and 49.50% after using the product for 2 weeks compared to before using the product. Accordingly, it can be seen that when cannabidiol is applied, the amount of transepidermal water loss decreases at a faster rate than when the cannabidiol is not applied, and the damaged skin barrier recovers more quickly.

Therefore, it was confirmed from Experimental Example 2 that when cannabidiol was applied, an improved skin barrier recovery effect could be exhibited.

Experimental Example 3. Evaluation of skin homeostasis maintenance for physical stimulation

In order to evaluate the recovery rate of the skin barrier damaged by physical stimulation, 21 female subjects with an average age of 49.2 years were physically destroyed using tape stripping, and then cannabidiol-containing products and cannabidiol The resilience to the application site of the free product was compared.

Specifically, tape stripping was performed 40 times on both forearm test sites of the subject using ANTERA 3D to induce physical skin stimulation. Then, a product containing 1.3 ppm of cannabidiol and a product with the same other composition but no cannabidiol were applied to each test site, showing redness of the skin before application and immediately after application once. The a* value change amount was measured, and the results are shown in Table 7.

Areas where cannabidiol-containing products are applied Areas where cannabidiol-free products are applied Before use (after stimulation) Immediately after 1 use Before use (after stimulation) Immediately after 1 use average
(n=21) 16.13 13.94 15.9 14.91

With the a* value change amount shown in Table 7, the a* value change improvement rate of the application site of the cannabidiol-containing product and the cannabidiol-free product of the corresponding product was calculated according to Equation 2 below, and the results are shown in Table 8 below. shown in

[Equation 2]

Improvement rate (%)= |measured value after use-measured value before use (after stimulation)| / Measured value before use (after stimulation) × 100

Areas where cannabidiol-containing products are applied Areas where cannabidiol-free products are applied Immediately after 1 use Immediately after 1 use Improvement rate (%) 13.63 6.22

As a result of analyzing the degree of improvement in the immediate skin irritation soothing effect caused by external stimulation (tape stripping 40 times) with only one use, the a* value representing the redness of the skin was compared to that before product application (after stimulation) without cannabidiol. Immediately after using the product once, a 6.22% reduction was shown, but immediately after using the product containing cannabidiol once, a reduction of 13.63% was shown.

Therefore, when cannabidiol was applied from Experimental Example 3, it showed an immediate skin soothing effect, confirming the improved skin barrier recovery effect.

Claims (8)

A cosmetic composition for maintaining skin barrier homeostasis, comprising cannabidiol as an active ingredient. According to claim 1,
The cannabidiol is a cosmetic composition for maintaining skin barrier homeostasis that is extracted from hemp seed oil. According to claim 1,
Maintaining the homeostasis of the skin barrier is a cosmetic composition for maintaining skin barrier homeostasis to restore the damaged skin barrier. According to claim 3,
Damage to the skin barrier is a cosmetic composition for maintaining skin barrier homeostasis that is caused by at least one selected from physical stimulation and chemical stimulation. According to claim 1,
The cosmetic composition for maintaining skin barrier homeostasis, characterized in that the composition promotes the expression of one or more genes selected from MT1H, CYP1A1, TNFRSF10D, and ALDH3a1. A cosmetic composition for improving the recovery rate of a skin barrier, comprising cannabidiol as an active ingredient. A quasi-drug composition for maintaining skin barrier homeostasis, comprising cannabidiol as an active ingredient. A quasi-drug composition for improving skin barrier recovery speed, comprising cannabidiol as an active ingredient.