WO2022168939A1 - Agent favorisant l'expression génique de la céramide synthase, agent améliorant la peau, aliment fonctionnel pour amélioration de la peau, produit cosmétique et procédé d'utilisation de dipeptide - Google Patents
Agent favorisant l'expression génique de la céramide synthase, agent améliorant la peau, aliment fonctionnel pour amélioration de la peau, produit cosmétique et procédé d'utilisation de dipeptide Download PDFInfo
- Publication number
- WO2022168939A1 WO2022168939A1 PCT/JP2022/004425 JP2022004425W WO2022168939A1 WO 2022168939 A1 WO2022168939 A1 WO 2022168939A1 JP 2022004425 W JP2022004425 W JP 2022004425W WO 2022168939 A1 WO2022168939 A1 WO 2022168939A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- gly
- ile
- skin
- ceramide synthase
- dipeptide
- Prior art date
Links
- 108010016626 Dipeptides Proteins 0.000 title claims abstract description 75
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- 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
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
Definitions
- the present invention relates to a method for using a ceramide synthase gene expression promoter, a skin quality improving agent, a functional food and cosmetic for improving skin quality, and a dipeptide.
- a beautiful and healthy skin is one of the important factors that bring out the attractiveness of a person's appearance. Therefore, skin care has been conventionally performed by both men and women.
- ingredients responsible for moisturizing the skin are important, and examples of such moisturizing ingredients include ceramide.
- Ceramide is a type of sphingolipid that is biosynthesized in cells, and is the main component of the stratum corneum that forms the surface of the epidermal layer of human skin. In addition, ceramide suppresses excessive evaporation of moisture and also acts as a barrier against microorganisms. need to keep
- ceramide synthesis promoters containing fungal cultures containing nicotinic acid and/or nicotinamide as active ingredients have been proposed.
- ceramide synthesis accelerator improvement of rough skin and improvement of various skin diseases can be expected by activating ceramide synthesis of the epidermal cells themselves within the skin surface layer and improving the skin barrier function.
- the present invention has been made in view of such circumstances, and a ceramide synthase gene capable of increasing the expression level of the ceramide synthase gene by employing a predetermined dipeptide as a main component for inducing function.
- An expression promoter is provided.
- the present invention also provides a skin quality improving agent, a functional food for improving skin quality, cosmetics, and a method of using the same dipeptide containing a predetermined dipeptide having a ceramide synthase gene expression promoting function.
- the ceramide synthase gene expression promoter according to the present invention contains a dipeptide represented by Gly-Ile and/or Ile-Gly as a main component for inducing function. did.
- the ceramide synthase gene expression promoter according to the present invention is also characterized in that the ceramide synthase gene is the ceramide synthase 3 (CERS3) gene.
- CERS3 ceramide synthase 3
- the skin quality-improving agent, functional food for skin quality improvement, and cosmetics according to the present invention contain a dipeptide represented by Gly-Ile and/or Ile-Gly as a main component for inducing function.
- a dipeptide represented by Gly-Ile and/or Ile-Gly is used as a main ingredient for inducing the function of a ceramide synthase gene expression promoter or as a participating ingredient for the purpose of improving skin quality. It was decided to.
- the dipeptide represented by Gly-Ile and/or Ile-Gly is contained as a main component for inducing function. It is possible to provide a ceramide synthase gene expression promoter that employs a predetermined dipeptide as a component and is capable of increasing the expression level of the ceramide synthase gene.
- the ceramide synthase gene is the ceramide synthase 3 (CERS3) gene, it is possible to target ceramide synthase 3, which is mainly expressed in skin and keratinocytes, and to achieve more efficient ceramide synthase 3. It can be used as a ceramide synthase gene expression promoter.
- CERS3 ceramide synthase 3
- the skin quality improving agent, skin quality improving functional food, and cosmetics according to the present invention contain a dipeptide represented by Gly-Ile and/or Ile-Gly as a main component for inducing function. , a skin quality improving agent, a functional food for improving skin quality, and a cosmetic that can increase the expression level of the ceramide synthase gene.
- a dipeptide represented by Gly-Ile and/or Ile-Gly is used as a main ingredient for inducing the function of the ceramide synthase gene expression promoter or as a participating ingredient for the purpose of improving skin quality. Since it was decided to use it, it is possible to enjoy the effect derived from the increase in the expression level of the ceramide synthase gene by the dipeptide represented by Gly-Ile and/or Ile-Gly.
- FIG. 4 is an explanatory diagram showing the cell viability of HaCaT cells by addition of each dipeptide.
- FIG. 4 is an explanatory diagram showing changes in the expression of ceramide synthase gene in HaCaT cells due to the addition of each dipeptide.
- FIG. 4 is an explanatory diagram showing changes in the expression of the ceramide synthase gene in HaCaT cells due to the addition of a small amount of dipeptide.
- FIG. 3 is an explanatory diagram showing the test results regarding the amount of water when the test food was ingested.
- FIG. 3 is an explanatory diagram showing the test results regarding the amount of transepidermal water loss when the test food was ingested.
- FIG. 3 is an explanatory diagram showing test results regarding total elasticity R2 of skin when test foods were ingested.
- FIG. 3 is an explanatory diagram showing test results regarding skin viscoelasticity (R5 (net elasticity)) when test foods were ingested.
- FIG. 3 is an explanatory diagram showing test results regarding skin recovery power R7 when a test food is ingested.
- the present invention provides a ceramide synthase gene expression promoter that employs a predetermined dipeptide as a main component for inducing function and is capable of increasing the expression level of the ceramide synthase gene.
- ceramide synthase gene expression promoter is not particularly limited. It can be used not only as an external agent but also, for example, as a reagent for testing and research.
- the promoter uses a dipeptide represented by Gly-Ile (glycine-isoleucine) and/or Ile-Gly (isoleucine-glycine) to induce function. contains as a major component of Gly-Ile (glycine-isoleucine) and/or Ile-Gly (isoleucine-glycine) to induce function. contains as a major component of Gly-Ile (glycine-isoleucine) and/or Ile-Gly (isoleucine-glycine) to induce function. contains as a major component of Gly-Ile (glycine-isoleucine) and/or Ile-Gly (isoleucine-glycine) to induce function. contains as a major component of Gly-Ile (glycine-isoleucine) and/or Ile-Gly (isoleucine-glycine) to induce function. contains as a major component of Gly-Ile (glycine-isoleucine) and/or Ile-Gly
- Gly-Ile and Ile-Gly are dipeptides in which glycine and isoleucine are peptide-bonded.
- the origin of Gly-Ile and Ile-Gly is not particularly limited. It may be of any origin as long as it does not contradict the purpose. In this specification, unless otherwise specified, the left side of the amino acid sequence is described as the N-terminus.
- Gly-Leu and Leu-Gly are known as dipeptides that are said to have a positive effect on the skin, but the dipeptide proposed in the present application is a substance that is structurally completely different from these substances, and It is clear from the test results described later that it has a higher ceramide synthase gene expression promoting effect than Gly-Leu or Leu-Gly.
- the skin quality improving agent is characteristic in that it contains a dipeptide represented by Gly-Ile and/or Ile-Gly as a main component for inducing function.
- the skin quality improving agent may be taken orally, or may be used as an external skin preparation.
- External agents for skin include pharmaceuticals, quasi-drugs, and cosmetics (including medicated cosmetics), but are not bound by these frameworks and are included in this concept as long as they are externally applied to the skin. .
- the present application also provides a cosmetic, which is one aspect of this external preparation for skin. That is, the cosmetic according to the present embodiment is characteristic in that it contains a dipeptide represented by Gly-Ile and/or Ile-Gly as an active ingredient.
- cosmetics include not only so-called makeup cosmetics, but also basic cosmetics, hair tonics, perfumes, toothpastes, shampoos, rinses, soaps and cleansers used for washing the body, and toiletry products such as bath agents. It also includes medicinal cosmetics claiming preventive effects.
- makeup cosmetics include foundations, eyebrows, mascara, eye shadows, eyeliners, lipsticks, glosses, cheeks, face powders, and nail polishes.
- Basic cosmetics include lotions, milky lotions, Facial cleansers, cleansers, serums, creams and the like can be mentioned. It should be noted that the above descriptions of external preparations for skin, cosmetics, and the like are examples of corresponding articles, etc., in order to facilitate understanding of the present invention, and the interpretation of each term is based on the articles, etc., listed above. It is not limited. However, it does not preclude the applicant from limiting the present invention to these articles and the like in obtaining the right of the present application.
- the present application also provides a method of using a dipeptide represented by Gly-Ile and/or Ile-Gly as a main component for inducing the function of a ceramide synthase gene expression promoter.
- a dipeptide represented by Gly-Ile and/or Ile-Gly as a main component for inducing the function of a ceramide synthase gene expression promoter.
- the present application also provides a method of using dipeptides represented by Gly-Ile and/or Ile-Gly as participating ingredients in functional foods for the purpose of improving skin quality.
- dipeptides represented by Gly-Ile and/or Ile-Gly as participating ingredients in functional foods for the purpose of improving skin quality.
- Several ingredients have been proposed to improve skin quality through oral ingestion. Not proposed.
- the present application also provides a functional food for improving skin quality, and in particular, provides a functional food for improving skin quality that can exert an excellent moisturizing effect on the skin when taken orally.
- Functional food is a concept that includes all foods that are said to contribute to the maintenance and promotion of health that do not contain pharmaceutical ingredients. It also includes food with health claims such as food for specified health use, food with nutrient function claims, and food with function claims.
- the dosage form is not particularly limited, and any dosage form such as tablets, capsules, fine granules, pills, lozenges, liquids, and jelly-like can be selected. can be done.
- Concentration of Gly-Ile and/or Ile-Gly as a component for inducing function to be contained in the ceramide synthase gene expression promoter, skin quality improving agent, functional food for improving skin quality, cosmetics, etc. according to the present embodiment is not particularly limited as long as the concentration is capable of inducing the above function.
- the concentration of Gly-Ile or Ile-Gly contained in the functional food for improving skin quality is, for example, an amount that allows 20 to 600 ⁇ g of Gly-Ile or Ile-Gly to be ingested per day, The total amount of Gly-Ile and Ile-Gly can be taken in an amount of 20 to 600 ⁇ g per day.
- the amount of Gly-Ile and/or Ile-Gly contained in one tablet is 20 to 600 ⁇ g. If two tablets are a guideline, the amount of Gly-Ile and/or Ile-Gly contained in the intake unit amount such as one tablet, one capsule, and one packet may be adjusted appropriately so that one tablet is 10 to 300 ⁇ g. It is possible.
- the cosmetic may contain 0.03 to 200 ⁇ g/g of Gly-Ile or Ile-Gly, or the total concentration of Gly-Ile and Ile-Gly may be 0.03 to 200 ⁇ g/g.
- concentrations of Gly-Ile and Ile-Gly in the ceramide synthase gene expression accelerator and the skin quality improving agent are adjusted to concentrations suitable for use in experiments, etc., and suitable as raw materials for the production of foods and cosmetics. concentration.
- the ceramide synthase gene expression promoter, skin quality improving agent, skin quality improving functional food, cosmetics, etc. may contain Gly-Ile and/or Ile-Gly as a component for inducing function.
- it may contain excipients, additives, auxiliary ingredients, and the like according to dosage forms, food forms, and the like.
- excipients examples include lactose, crystalline cellulose, and starch when the dosage form is a solid formulation.
- additives include stabilizers, surfactants, solubilizers, plasticizers, sweeteners, antioxidants, flavoring agents, coloring agents, preservatives, inorganic fillers, and the like.
- the skin is composed of the epidermis and dermis, which are divided into the stratum basale, the stratum spinosum, the stratum granulosum and the stratum corneum.
- a lamellar structure composed of lipids such as ceramides between stratum corneum cells located in the outermost layer of the skin plays a role as a physical barrier to retain water in the body and prevent invasion of bacteria and viruses.
- Gly-Ile and Ile-Gly (hereinafter also referred to as the dipeptide of the present application) on epidermal cells was evaluated by examining changes in the expression level of the ceramide synthase gene.
- Gly-Leu and Leu-Gly (hereinafter also referred to as comparative dipeptides) were used as controls for comparison, and differences from the dipeptides of the present application were also examined.
- HaCaT cells Human epidermal keratinocytes (HaCaT cells) were cultured in ⁇ 10 cm dishes using Dulbecco's Modified Eagle Medium (DMEM) (high glucose) (containing 1% penicillin-streptomycin and 10% fetal bovine serum (FBS)) until confluent. was pre-cultured.
- DMEM Dulbecco's Modified Eagle Medium
- FBS fetal bovine serum
- the cells were washed with phosphate buffered saline (PBS), resuspended in medium, seeded in a 24-well plate at a concentration of 1.0 ⁇ 10 5 cells/well, and placed in a CO 2 incubator (37°C, 5% CO 2 ). was cultured overnight.
- PBS phosphate buffered saline
- serum-free DMEM high glucose
- penicillin-streptomycin containing either Gly-Ile, Ile-Gly, Gly-Leu, or Leu-Gly at a predetermined final concentration
- cDNA was synthesized from the extracted total RNA using ReverTra Ace qPCR RT Master Mix with gDNA Remover (TOYOBO).
- TOYOBO ReverTra Ace qPCR RT Master Mix with gDNA Remover
- 5'-CCGATTACCTGCTGGAGTCAG-3' SEQ ID NO: 1
- 5'-GGCGAAGACGATGAAGATGTTG-3' SEQ ID NO: 2
- FIG. 1 shows the cell viability of HaCaT cells with the addition of each dipeptide.
- FIG. 2 shows changes in the expression of the ceramide synthase gene in HaCaT cells with the addition of the dipeptides of the present application, Ile-Gly and Gly-Ile, and the comparative dipeptides, Leu-Gly and Gly-Leu.
- FIG. 2(a) shows the expression level of the ceramide synthase CERS2 gene relative to the control, similarly FIG. 2(b) shows the expression level of the ceramide synthase CERS3 gene, and FIG. is shown as a relative value.
- the ceramide synthase CERS2 gene is highly expressed in many cell tissues such as kidney, liver and intestine.
- the ceramide synthase CERS3 gene is mainly expressed in skin and keratinocytes.
- the ceramide synthase CERS4 gene is expressed not only in skin but also in leukocytes, heart and liver.
- the addition of Gly-Ile showed a significant concentration-dependent increase in the expression level, and it is extremely interesting that at a concentration of 200 ⁇ g/mL, the expression level increased 3-fold compared to the control.
- ceramide synthase CERS4 gene As shown in Fig. 2(c), a marked increase in the expression level was confirmed with the addition of Gly-Ile.
- the dipeptide of the present application can be expected to have a cell activating effect, and that it has the effect of enhancing the expression of the ceramide synthase CERS3 and CERS4 genes. It was also suggested that this effect is particularly high with Gly-Ile among the dipeptides of the present application.
- the dipeptide of the present application is found to have the effect of promoting the expression of the ceramide synthase gene, and is expected to have the effect of promoting ceramide synthesis, which plays an important role in the skin barrier function.
- the dipeptide represented by Gly-Ile and/or Ile-Gly is a main component for inducing function in skin quality improving agents, a component involved in improving skin quality in functional foods, and a cosmetic component. It was shown that it can be used as an active ingredient for improving skin quality in cosmetics.
- sample solution S1 containing at least 0.00038 ⁇ g/mL of Gly-Ile and at least 0.00097 ⁇ g/mL of Ile-Gly with a total concentration of both dipeptides of 0.00135 ⁇ g/mL and of Gly-Ile and at least 0.00195 ⁇ g/mL of Ile-Gly, with a total concentration of both dipeptides of 0.00271 ⁇ g/mL (double concentration solution of sample solution S1) and at least 0.00152 ⁇ g/mL of Ile-Gly.
- Sample solution S3 containing 1 mL of Gly-Ile and at least 0.0039 ⁇ g/mL of Ile-Gly and having a total concentration of 0.00542 ⁇ g/mL of both dipeptides was used as the test solution.
- 1 mL of final serum-free DMEM (high glucose) (containing 1% penicillin-streptomycin) constituting any of the above test solutions was added to each well, and placed in a CO 2 incubator (37°C). , 5% CO 2 ) for 48 hours.
- Fig. 3(a) shows the cell viability of HaCaT cells with the addition of each sample solution S1 to S3. As shown in FIG. 3(a), no significant difference was observed between the sample solutions S1 to S3 and the control.
- Fig. 3(b) shows changes in the expression of the ceramide synthase gene in HaCaT cells after the addition of each sample solution S1 to S3.
- the CERS3 and CERS4 genes which have been reported to be expressed in the skin, were upregulated by about 2 to 4 times compared to controls.
- the CERS3 gene showed a more pronounced increase in expression compared to the CERS4 gene.
- Gly-Ile and Ile-Gly which are the dipeptides of the present application, have no cytotoxicity and have the effect of enhancing the expression of the ceramide synthase CERS3 and CERS4 genes. Therefore, Gly-Ile and Ile-Gly, which are the dipeptides of the present application, can be expected to promote ceramide synthesis, which plays an important role in skin barrier function, at a total concentration of 0.00135 ⁇ g/mL or higher.
- the total concentration of both dipeptides is 0.03 ⁇ g/mL. can be effective.
- the dosage form of the functional food for testing was a hard capsule. Specifically, 200 mg of powdered dextrin is used as a base material, Gly-Ile and/or Ile-Gly obtained by peptide synthesis are added and mixed, and the obtained mixed powder is used as a capsule with gelatin as a shell material. The body was filled and capped to obtain a functional food A in the form of a hard capsule.
- Table 4 shows the dipeptide content of functional food A using a calibration curve. It was confirmed that one grain of functional food A contained 26.25 ⁇ 0.38 ⁇ g of Gly-Ile and 22.57 ⁇ 0.48 ⁇ g of Ile-Gly.
- test was conducted on 20 healthy general women aged 40 to 50, divided into 2 groups: 10 test product groups and 10 placebo groups.
- the intake was 2 tablets per day for both the test product group (functional food A) and the placebo group (placebo food).
- the placebo food does not contain Gly-Ile and Ile-Gly.
- the ingestion period was 4 weeks.
- the skin quality was measured after the ingestion period. Specifically, the water content, water loss, and viscoelasticity of the skin were measured. The measurement site was the left arm.
- the standard error was calculated, and a paired t-test and an unpaired t-test were performed for comparison between pre-measurement and post-measurement (within-group comparison) and between-group comparisons.
- the significance level was set to 5%, and less than 5% was judged to have a significant difference (p ⁇ 0.05:**), and less than 10% was judged to have a significant tendency (p ⁇ 0.1:*).
- FIG. 4 shows test results regarding water content.
- the water content is the amount of water contained in the stratum corneum, and is a value referred to as an index of skin moisture.
- FIG. 4(a) shows changes in water content measurements before and after ingestion of the test food or placebo food
- FIG. 4(b) shows changes in water content in the placebo group and the test product group, respectively. .
- Fig. 5 shows the test results regarding transepidermal water loss.
- the transepidermal water loss is the amount of water that evaporates from the surface of the skin, and is an indicator of the barrier function.
- Figure 5 (a) shows the change in transepidermal water loss before and after ingestion of the test food or placebo food
- Figure 5 (b) shows the change in the amount of transepidermal water loss between the placebo group and the test product group. each shown.
- FIG. 6 shows the test results regarding the total skin elasticity (R2).
- Total elasticity is an index representing the overall elasticity of the skin. Skin elasticity is maintained by the fiber and water-retaining components of the dermis layer.
- FIG. 6(a) shows changes in total elasticity before and after ingestion of the test food or placebo food
- FIG. 6(b) shows changes in total elasticity of the placebo group and the test article group, respectively.
- FIG. 7 shows the test results regarding skin viscoelasticity (R5 (net elasticity)). Viscoelasticity is a value that serves as an index of skin firmness and elasticity.
- FIG. 7(a) shows changes in viscoelasticity before and after ingestion of the test food or placebo food
- FIG. 7(b) shows changes in viscoelasticity between the placebo group and the test product group, respectively.
- Fig. 8 shows test results regarding skin recovery power R7 (return rate).
- the resilience is a value representing the instantaneous contraction rate with respect to the stretched length of the skin at the time of suction, and shows a high correlation with firmness and sagging of the skin.
- FIG. 8(a) shows changes in resilience before and after ingestion of the test food or placebo food
- FIG. 8(b) shows changes in resilience between the placebo group and the test article group, respectively.
- the ceramide synthase gene expression promoter contains a dipeptide represented by Gly-Ile and/or Ile-Gly as a main component for inducing function. It is possible to provide a ceramide synthase gene expression-promoting agent that employs a predetermined dipeptide as a main component for inducing function and that is capable of increasing the expression level of the ceramide synthase gene.
- the skin quality improving agent, skin quality improving functional food, and cosmetics according to the present embodiment contain a dipeptide represented by Gly-Ile and/or Ile-Gly as a main component for inducing function. Therefore, it is possible to increase the expression level of the ceramide synthase gene, and use it as a skin quality improving agent, a functional food for improving skin quality, or a cosmetic that can improve skin quality.
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Abstract
L'invention concerne un agent favorisant l'expression génique de la céramide synthase dans lequel un dipeptide prescrit est utilisé comme ingrédient principal pour provoquer une fonction, et qui est capable d'augmenter le niveau d'expression d'un gène de céramide synthase. Un dipeptide représenté par Gly-Ile et/ou Ile-Gly est contenu en tant qu'ingrédient principal pour provoquer une fonction. La présente invention est également caractérisée en ce que le gène de céramide synthase est le gène de la céramide synthase 3 (CERS3).
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JP2021017246A JP2022120386A (ja) | 2021-02-05 | 2021-02-05 | セラミド合成酵素遺伝子発現促進剤、肌質改善剤、肌質改善用機能食品及び化粧料並びにジペプチドの使用方法 |
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WO2011126163A1 (fr) * | 2010-04-08 | 2011-10-13 | 주식회사 웰스킨 | Composition de blanchiment de la peau contenant un dipeptide |
JP2012522043A (ja) * | 2009-03-31 | 2012-09-20 | ウェルスキン カンパニー,リミテッド | ジペプチドを有効成分として含む紫外線による紅斑反応抑制組成物 |
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JP2012522043A (ja) * | 2009-03-31 | 2012-09-20 | ウェルスキン カンパニー,リミテッド | ジペプチドを有効成分として含む紫外線による紅斑反応抑制組成物 |
WO2011126163A1 (fr) * | 2010-04-08 | 2011-10-13 | 주식회사 웰스킨 | Composition de blanchiment de la peau contenant un dipeptide |
Non-Patent Citations (2)
Title |
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NAGAE MASUMI, ET AL: "Effect of Porcine Placenta Extract Supplement on Skin Condition in Healthy Adult Women: A Randomized, Double-Blind Placebo-Controlled Study", NUTRIENTS, vol. 12, no. 6, pages 1671, XP055957223, DOI: 10.3390/nu12061671 * |
PARK JONG IL, ET AL: "Oral Administration of Glycine and Leucine Dipeptides Improves Skin Hydration and Elasticity in UVB-Irradiated Hairless Mice", BIOMOLECULES & THERAPEUTICS, vol. 25, no. 5, 1 September 2017 (2017-09-01), pages 528 - 534, XP055957225, ISSN: 2005-4483, DOI: 10.4062/biomolther.2017.089 * |
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