Composition for promoting collagen production

Abstract

The objective is to provide a novel composition that promotes collagen production. [Solution] As a result of diligent research, the present inventors have found that a composition containing peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline promotes collagen production. Therefore, this disclosure provides a composition containing peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline.

Description

Technical Field

[0001] The present disclosure relates to a composition for promoting collagen production.

Background Art

[0002] The skin is composed of the stratum corneum, epidermis, dermis, and subcutaneous tissue from the outside, and the dermis is the largest part in terms of area. In the dermis, collagen fibers, elastic fibers, proteoglycans, etc. form a complex three-dimensional structure, and each structure forms a complex network structure with each other. The components of the dermis mainly consist of collagen called collagen fibers, and among them, type I collagen accounts for about 80% of the entire dermis. In addition to type I collagen, various types of collagen such as type III, V, XII, and XIV are known to exist in the collagen that constitutes the skin. Dermal fibroblasts that produce collagen have a decreasing ability to produce collagen with aging. For this reason, it is considered that the entire skin tissue becomes thinner, causing wrinkles and sagging in appearance. The occurrence of wrinkles and sagging is the main visible sign of aging, and for many middle-aged and elderly people, it is an aesthetically urgent problem. Therefore, research has been conducted on compositions that promote the production of collagen in order to improve wrinkles and sagging (Patent Document 1).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] An object is to provide a novel composition that promotes the production of collagen.

Means for Solving the Problems

[0005] As a result of diligent research, the inventors have found that a composition containing peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline promotes collagen production. Therefore, the present invention relates to the following. [1] A composition comprising peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline. [2] The composition described in item 1, comprising 0.0001% to 10% by mass of peony extract, 0.0001% to 10% by mass of rose extract, 0.0001% to 10% by mass of Bupleurum falcatum extract, and 0.000001% to 0.1% by mass of L-hydroxyproline. [3] The composition according to item 1 or 2, further comprising retinol or a retinol derivative. [4] The composition according to item 3, comprising 0.000001% to 1% by mass of retinol or a retinol derivative. [5] The compositions described in items 1 to 4 for promoting collagen production. [6] The composition according to item 5, which promotes collagen production in the dermal papillary layer. [7] The composition according to item 6, wherein the collagen in the dermal papillary layer is one collagen selected from the group consisting of type I collagen, type III collagen, and type V collagen, or a combination thereof. [8] A wrinkle-improving agent comprising the composition described in item 5. [9] A skin tightening agent comprising the composition described in item 5.

[10] Acupuncture correcting agent comprising the composition described in item 5.

[11] A transdermal composition comprising the composition described in item 5.

[12] The composition according to item 11, wherein the transdermal composition is a cosmetic composition. [Effects of the Invention]

[0006] The present composition, comprising peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline, promotes collagen production. [Brief explanation of the drawing]

[0007] [Figure 1] Figure 1 shows the expression of COL1A1, COL3A1, and COL5A1 in cultured human fibroblasts under the following conditions: control (no retinol or extract-containing composition added), retinol only, peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline (extract-containing composition) only, and extract-containing composition and retinol added. [Modes for carrying out the invention]

[0008] This disclosure relates to a composition comprising peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline. Such composition can be used for topical application to the skin. The composition can promote collagen production, particularly the production of type I collagen, type III collagen, and / or type V collagen.

[0009] Human skin is composed of the stratum corneum, epidermis, dermis, and subcutaneous tissue, with the dermis occupying the largest area. Type I and Type III collagen are abundant in the dermis, and their production is known to decrease with age due to factors such as the decline in fibroblast function. This decrease is thought to cause a loss of skin elasticity (flexibility), leading to wrinkles and sagging. Type V collagen is found in the reticular layer, a region directly beneath the basement membrane at the junction of the epidermis and dermis. Therefore, promoting the production of Type I, Type III, and / or Type V collagen can improve wrinkles, sagging, and skin firmness.

[0010] Collagen accounts for approximately 30% of the body protein in animals and is a major protein that makes up not only the skin but also bones, teeth, and tendons. Collagen has a distinctive amino acid composition, with glycine accounting for one-third of the total amino acids and the combined amount of hydroxyproline and proline accounting for one-quarter of the total amino acids. In addition, collagen contains hydroxylysine and hydroxyproline as special amino acids not found in general proteins. Nearly 30 types of collagen have been identified in vertebrates, and each type has different constituent molecules. For example, type I collagen is composed of α1 and α2 chains, which are the expression products of two genes, COL1A1 and COL1A2. Type III collagen is composed of three α1 chains, which are the expression products of the COL3A1 gene. Type V collagen is composed of α1, α2, and α3 chains, which are the expression products of the COL5A1, COL5A2, and COL5A3 genes.

[0011] The present composition, comprising peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline, increases the gene expression of COL1A1 and COL3A1 in human dermal fibroblasts. Furthermore, when combined with retinol, it further promotes the gene expression of COL1A1, COL3A1, and / or COL5A1 (Figure 1). The COL1A1 gene expresses the α1(I) chain, a component of type I collagen, and is involved in the production of type I collagen. The COL3A1 gene expresses the α1(III) chain, a component of type III collagen, and is involved in the production of type III collagen. The COL5A1 gene expresses the α1(V) chain, a component of type V collagen, and is involved in the production of type V collagen. Accordingly, the compositions of this disclosure promote the production of type I collagen, type III collagen, and / or type V collagen. In addition, by promoting the production of type I collagen, type III collagen, and / or type V collagen, wrinkles, sagging, and firmness are improved.

[0012] The plant extracts described herein can be obtained by conventional methods, for example, by immersing or refluxing the source plant with an extraction solvent at room temperature or under heating, followed by filtration and concentration. Any solvent commonly used for extraction can be used as the extraction solvent, such as aqueous solvents, e.g., water, physiological saline, phosphate buffer, borate buffer, or organic solvents, e.g., alcohols such as ethanol, propylene glycol, 1,3-butylene glycol, glycerin, aqueous alcohols, chloroform, dichloroethane, carbon tetrachloride, acetone, ethyl acetate, hexane, etc., each can be used alone or in combination. Preferably, a mixed solvent of water and alcohol, such as 1,3-butylene glycol, is used as the solvent. The extract obtained by extraction with the above solvent can be used as is, or concentrated by methods such as freeze-drying. If necessary, an extract obtained by adsorption, for example, by removing impurities using an ion exchange resin, or by adsorption using a porous polymer (e.g., Amberlite XAD-2) column, followed by elution with a desired solvent and further concentration can also be used. The plant extracts used can be commercially available extracts used as cosmetic ingredients, and these commercially available extracts can be incorporated at a predetermined concentration.

[0013] Peony extract is an extract obtained from plants belonging to the genus Paeonia in the family Paeoniaceae. Furthermore, in the labeling names used for the full ingredient list of cosmetics as defined by the Japan Cosmetic Industry Association, and in the international labeling names according to INCI (International Nomenclature for Cosmetic Ingredients), it is represented as: Peony Root Extract / PAEONIA ALBIFLORA ROOT EXTRACT. Examples of plants belonging to the genus Paeonia include peony (Paeonia lactiflora Pall.) and peony (Paeonia suffruticosa). Peony is native to northern China, but is distributed from eastern Siberia to northern China. The plant part may be the leaves, stems, flowers, roots, or fruits, but flowers and / or roots are particularly used. It can be prepared by extracting the plant part, especially the flowers and / or roots, using water, alcohol, or a mixture thereof. Alcohols used include ethanol, glycerol, propylene glycol, and / or butylene glycol. More preferably, the product can be extracted with a mixture of water and alcohol, such as 1,3-butylene glycol, in any proportion, for example, a mixture of 10:90 to 90:10, preferably 30:70 to 70:30, and even more preferably 50:50.

[0014] European rose extract is an extract obtained from plants belonging to the genus Rosa in the family Rosaceae. Furthermore, in the labeling names used for the full ingredient list of cosmetics as defined by the Japan Cosmetic Industry Association, and in the international labeling names according to INCI (International Nomenclature for Cosmetic Ingredients), it is represented as: Centifolia rose flower extract / ROSA CENTIFOLIA FLOWER EXTRACT. Examples of plants belonging to the genus Rosa include wild rose (Rosa multiflora) and Japanese rose (Rosa rugosa). European rose is a horticultural variety of rose with complex hybrid characteristics, developed through long-term breeding and improvement. European rose was created through crossbreeding of many species, primarily Damask rose, musk rose, French rose (native to Western Asia and Europe), Chinese rose (Rosa kosinensis), peony rose (native to China), and Japanese wild rose (Rosa japonica) and luscious wild rose (Rosa luciae). While leaves, stems, flowers, roots, and fruits can be used as part of the plant, flowers are particularly commonly used. Plants, especially flowers, can be prepared by extraction using water, alcohol, or a mixture thereof. Suitable alcohols include ethanol, glycerol, propylene glycol, and butylene glycol. More preferably, the extraction can be performed using a mixture of water and alcohol, such as 1,3-butylene glycol, in any ratio, for example, a mixture of 10:90 to 90:10, preferably 30:70 to 70:30, and even more preferably 50:50.

[0015] Bupleurum falcatum root extract is an extract obtained from plants belonging to the genus Bupleurum in the family Apiaceae. According to the Japan Cosmetic Industry Association's guidelines for ingredient labeling in cosmetics and the International Nomenclature for Cosmetic Ingredients (INCI), it is represented as Bupleurum falcatum root extract. Examples of plants belonging to the Bupleurum genus include Bupleurum stenophyllum and Bupleurum longiradiatum var. elatius. Bupleurum falcatum is native to Japan, China, and the Korean Peninsula. The plant can be used as an extractant from leaves, stems, flowers, roots, or fruits, but leaves are particularly commonly used. It can be prepared by extracting the plant, especially the leaves, with water, alcohol, or a mixture thereof. Ethanol, glycerol, propylene glycol, and butylene glycol are commonly used as alcohols. More preferably, the product can be extracted with a mixture of water and alcohol, such as 1,3-butylene glycol, in any proportion, for example, a mixture of 10:90 to 90:10, preferably 30:70 to 70:30, and even more preferably 50:50.

[0016] Commercially available L-hydroxyproline can be used. L-hydroxyproline, also known as "(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid", is an amino acid that constitutes structural proteins of animals, such as collagen and elastin. Its effects include promoting the production of collagen in fibroblasts, promoting the proliferation of epidermal cells, and having a moisturizing effect equal to or greater than that of collagen, etc. Its physiologically acceptable salt forms include, for example, alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, and aluminum salts; various organic amines, that is, amine salts formed from aliphatic or arylaliphatic primary, secondary or tertiary mono-, di- or polyamines or heterocyclic bases, such as triethylamine, 2-hydroxyethylamine, di-(2-hydroxyethyl)amine, tri-(2-hydroxyethyl)amine, 4-aminobenzoic acid-2-diethylaminoethyl ester, 1-ethylpiperidine, bicyclohexylamine, N,N'-dibenzyl-ethylenediamine, pyridine, collidine, quinoline, procaine, dibenzylamine, 1-ephenamine and salts derived from N-alkyl-piperidine, etc., but are not limited thereto. The structure of L-hydroxyproline is shown below. [Chemical formula]

[0017] In one aspect of this disclosure, the composition may contain 0.0001% to 10% peony extract, 0.0001% to 10% rose extract, 0.0001% to 10% Bupleurum falcatum extract, and 0.000001% to 0.1% L-hydroxyproline. The peony extract is contained in the composition at a concentration of 0.001% to 1%, preferably 0.01% to 0.3%, and more preferably 0.03% to 0.2%. The rose extract is contained in the composition at a concentration of 0.001% to 1%, preferably 0.01% to 0.3%, and more preferably 0.03% to 0.2%. Bupleurum falcatum extract is contained in the present composition at a concentration of 0.0001% to 0.1%, preferably 0.001% to 0.03%, and more preferably 0.003% to 0.02%. L-hydroxyproline is contained in the present composition at a concentration of 0.00001% to 0.01%, preferably 0.0001% to 0.003%, and more preferably 0.0003% to 0.002%. The optimal blending ratio of each extract is 1:1:0.1:0.01 for peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline, and it is also possible to add 0.0001% to 10% of this optimal blending ratio composition.

[0018] From the perspective of further promoting the gene expression of COL1A1, COL3A1, and / or COL5A1, the composition of the present application may further contain retinol or a retinol derivative. Retinol alone could not significantly promote the gene expression of COL1A1, COL3A1, and COL5A1 (Figure 1). On the other hand, a combination of Paeonia lactiflora extract, Rosa centifolia extract, Psychotria serpens extract, and L-hydroxyproline and retinol promotes the gene expression of COL1A1, COL3A1, and COL5A1 in human fibroblasts, and a synergistic effect is exerted (Figure 1). Retinol or a retinol derivative is not particularly limited as long as it can be used in the fields of cosmetics, pharmaceuticals, quasi-drugs, etc. Examples of retinol derivatives include retinol palmitate, retinol acetate, retinal, tretinoin, isotretinoin, retinoic acid, retinol propionate, retinol linoleate, hydrogenated retinol, etc. Retinol or a retinol derivative is contained in the composition of the present application at a concentration of 0.000001% to 1%, preferably 0.0001% to 0.1%, and more preferably 0.01% to 0.1%.

[0019] The composition consisting of Paeonia lactiflora extract, Rosa centifolia extract, Psychotria serpens extract, and L-hydroxyproline and retinol or its derivative can be formulated at a mixing ratio of 1:0.0000001 to 1:10000 in terms of weight percentage in the optimal formulation composition. From the perspective of fully exerting the effect of collagen production, preferably, it can be formulated at a mixing ratio of 1:0.0001 to 1:10.

[0020] In another aspect of this disclosure, the composition may be used to promote collagen production. The composition can act on the dermis, particularly the dermal papillary layer, by topical application, especially to the skin, especially the skin of the face. Collagen production promotion may involve promoting the expression of one collagen selected from the group consisting of type I collagen, type III collagen, and type V collagen, or a combination thereof, in the dermal papillary layer. Type III collagen and type V collagen are collagens that are abundant in the dermal papillary layer, and it is thought that type I collagen, type III collagen, and type V collagen work together to create thin and flexible collagen fibers. Therefore, by simultaneously promoting the expression of type I collagen, type III collagen, and type V collagen, the synthesis of collagen fibers can be promoted in the dermal papillary layer.

[0021] In another aspect of this disclosure, the present composition for promoting collagen production can improve wrinkles, sagging, and firmness by promoting the production of type I collagen, type III collagen, and type V collagen. Therefore, a wrinkle-improving agent, a sagging-improving agent, and a firmness-improving agent containing the present composition for promoting collagen production may also be used.

[0022] In yet another aspect of this disclosure, a transdermal composition comprising a wrinkle-improving agent, a sagging-improving agent, and a firming agent, comprising the present composition for promoting collagen production, may also be used. The transdermal composition is not particularly limited as long as it is applicable to the skin, and any dosage form can be applied, such as solution, emulsion, solid, semi-solid, powder, powder dispersion, water-oil two-layer separation, water-oil-powder three-layer separation, ointment, gel, aerosol, mousse, stick, etc. The transdermal composition may contain a base commonly used in transdermal compositions, and excipients, such as preservatives, emulsifiers, and pH adjusters.

[0023] The aforementioned composition may be a cosmetic composition. When incorporated into a cosmetic composition, it can be used in facial or body cosmetics such as lotions, emulsions, serums, creams, packs, essences, and gels, as well as makeup cosmetics such as foundations, makeup bases, and concealers, and even bath additives. The composition containing peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline, and retinol or its derivatives may be incorporated into the same composition and applied simultaneously, or they may be applied at different times.

[0024] The collagen production-promoting composition of the present disclosure can be applied to the skin in cosmetic methods to improve wrinkles, sagging, and / or firmness. The methods of the present disclosure do not include medical procedures, i.e., surgeries, treatments, or diagnoses performed on humans by a physician or their authorized representative, and may be considered non-medical procedures. The use and dosage of the transdermal composition of the present disclosure in such cosmetic methods are not particularly limited. Typically, an appropriate amount, e.g., 1 to 1.5 mL, can be rubbed directly into the skin of the entire face several times a day, for example, 1 to 3 times, or an appropriate amount can be soaked into a cotton pad or sheet mask and then applied to the skin.

[0025] All references made herein are incorporated herein by reference in their entirety. Unless otherwise specified herein, % refers to mass %. For extracts, commercially available liquids are used and diluted, but the calculation can be done by assuming a specific gravity of 1 and expressing it as mass %.

[0026] The embodiments of the Disclosure described below are for illustrative purposes only and do not limit the technical scope of the Disclosure. The technical scope of the Disclosure is limited solely by the claims. Modifications to the Disclosure, such as adding, deleting, or replacing constituent elements of the Disclosure, may be made without departing from the spirit of the Disclosure. [Examples]

[0027] Example 1: Fibroblast culture Human dermal fibroblasts were seeded in a T75 flask containing DMEM with 10% FBS and cultured at 37°C under 5% CO2 conditions. After harvesting the cells, 56,000 cells per well were seeded into a 96-well plate and cultured overnight. Subsequently, the cells were cultured for 24 hours in DMEM containing 0.5% FBS. Next, the cells were cultured in DMEM containing 50 μg / mL ascorbic acid and 0.5% FBS, with or without the addition of 0.1% peony extract (Maruzen Pharmaceutical Co., Ltd.), 0.1% rose extract (Ichimaru Falcos Co., Ltd.), 0.01% Bupleurum falcatum extract (Maruzen Pharmaceutical Co., Ltd.), and 0.001% L-hydroxyproline (Nikko Chemicals Co., Ltd.). After a further 48 hours, the cells were cultured in DMEM containing 50 μg / mL ascorbic acid and 0.5% FBS, with or without the addition of 30 μM retinol. After culturing for 48 hours, the cells were harvested. Example 2: Gene expression analysis Total RNA was extracted from the fibroblasts recovered in step 1, and cDNA was prepared using the TaqMan Gene Expression Cells-to-CT Kit (Thermo Fisher Scientific) according to the described protocol. The reverse-transcribed samples were subjected to real-time PCR using the TaqMan Gene Expression Master Mix (Thermo Fisher Scientific) and the quantitative kits described below. The gene expression levels of COL1A1, COL3A1, and COL5A1 were evaluated by the ddCt method as relative levels to the internal standard gene βactin (ACTB) (Figure 1). [Table 1]

Claims

1. A composition comprising peony extract, rose extract, Bupleurum falcatum extract, and L-hydroxyproline.

2. The composition according to claim 1, comprising 0.0001% to 10% by mass of peony extract, 0.0001% to 10% by mass of rose extract, 0.0001% to 10% by mass of Bupleurum falcatum extract, and 0.000001% to 0.1% by mass of L-hydroxyproline.

3. The composition according to claim 1, further comprising retinol or a retinol derivative.

4. The composition according to claim 3, comprising 0.000001% by mass to 1% by mass of retinol or a retinol derivative.

5. A composition according to any one of claims 1 to 3 for promoting collagen production.

6. The composition according to claim 5, which promotes collagen production in the dermal papillary layer.

7. The composition according to claim 6, wherein the collagen in the dermal papillary layer is one collagen selected from the group consisting of type I collagen, type III collagen, and type V collagen, or a combination thereof.

8. A wrinkle-improving agent comprising the composition described in claim 5.

9. A sagging-improving agent comprising the composition described in claim 5.

10. A needle-improving agent comprising the composition described in claim 5.

11. A transdermal composition comprising the composition described in claim 5.

12. The composition according to claim 11, wherein the transdermal composition is a cosmetic composition.

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