Combinations for promoting protein production

Abstract

This provides a combination for promoting protein production. [Solution] According to one embodiment, a collagen production promoter comprising crowberry is provided for use in combination with hibiscus or a composition comprising hibiscus. Such a collagen production promoter comprising crowberry may also be a composition comprising crowberry for promoting collagen production. Such promotion of collagen production may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

Description

Technical Field

[0001] The present invention relates to a combination for promoting protein production.

Background Art

[0002] The skin is composed of the stratum corneum, epidermis, basement membrane, and dermis from the outside. The dermis is the largest part among them, and it is not as densely packed with cells as the epidermis. Rather, it has more extracellular space and is filled with a network structure of macromolecules called the "extracellular matrix". This extracellular matrix is produced by fibroblasts in the dermis and is composed of polysaccharides called acidic mucopolysaccharides such as hyaluronic acid and dermatan sulfate, and fibrous proteins such as collagen and elastin. The extracellular matrix is directly involved in the elasticity, firmness, moisture, and metabolism of the skin. When the production of the extracellular matrix in fibroblasts and the like is reduced, the elasticity and moisture of the skin are lost, and wrinkles, fine lines, and rough skin are likely to occur, contributing to skin aging.

[0003] The above fibrous protein mainly consists of collagen, and among them, type I collagen accounts for 80% of the whole. In addition to type I collagen, the presence of types III, V, XII, and XIV collagen is known. One of the causes of wrinkles and sagging seen in aging skin is the thinning of skin tissue with aging. In aging skin, the decrease in collagen fibers, which are the main matrix components of the dermis, is remarkable, and this is likely to be the main cause of the decrease in skin thickness. Therefore, promoting the production of collagen and maintaining the amount of collagen is considered effective for preventing and improving wrinkles and sagging. In addition to the above, promoting the production of collagen is also considered effective for improving wound healing of the skin and the like.

[0004] As a component having such an effect of promoting collagen production, for example, N-benzoylglycylglycine and the like have been reported (Patent Document 1).

[0005] Furthermore, it has been reported that fibroblasts present in the dermis proliferate well within damaged tissue and work in coordination with mesenchymal stem cells (MSCs) to promote wound healing (Non-Patent Document 1), and that stabilizing mesenchymal stem cells in the skin is effective for skin activation and anti-aging (Patent Documents 2 and 3).

[0006] Platelet-derived growth factor-bb (PDGF-bb) has been reported as a factor that stabilizes mesenchymal stem cells (Patent Documents 2 and 3). Therefore, if a component effective in enhancing PDGF-bb production can be found, it is expected that this can be used to stabilize mesenchymal stem cells and, consequently, be effectively used for applications such as skin activation and anti-aging.

[0007] Examples of ingredients that have been reported to be effective in promoting the production of PDGF-bb include retinoic acid, amla extract, and lingonberry extract (Patent Documents 2 and 3). [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Japanese Patent Publication No. 2014-055116 [Patent Document 2] International Publication No. 2012 / 036211 [Patent Document 3] Japanese Patent Publication No. 2013-001669 [Non-patent literature]

[0009] [Non-Patent Document 1] Progress in Medicine Vol 272(10), 988-993 (2020) [Overview of the project]

[0010] This invention provides a combination for promoting protein production.

[0011] The inventors have discovered that the production of collagen and PDGF-bb can be effectively promoted by a specific combination of materials. This invention is based on this finding.

[0012] The present invention provides the following: (1) A composition comprising crowberry for promoting collagen production, for use in combination with hibiscus or corn silk. (2) A composition for promoting collagen production, comprising hibiscus or corn silk, for use in combination with crowberry. (3) A composition for promoting collagen production, comprising crowberry and hibiscus or corn silk. (4) A composition comprising crowberry for promoting the production of PDGF-bb, for use in combination with hibiscus or corn silk. (5) A composition comprising hibiscus or corn silk for promoting the production of PDGF-bb, for use in combination with crowberry. (6) A composition for promoting the production of PDGF-bb, comprising crowberry and hibiscus or corn silk. (7) A composition according to any one of (1) to (6) for improving skin firmness. (8) A composition according to any one of (1) to (7) for use in which CA / CB is 0.1 to 10, where CA is the dry weight of the black soybean and CB is the dry weight of the hibiscus. (9) A composition according to any one of (1) to (7) for use such that CA / CD is 0.1 to 10, where CA is the dry weight of the black soybean and CD is the dry weight of the corn silk. (10) A composition for oral use, as described in any of (1) to (9). (11) A composition comprising chrysanthemum for promoting collagen production, for use in combination with Cassia seed or Polygonatum odoratum. (12) A composition for promoting collagen production, comprising Cassia seed or Polygonatum odoratum, for use in combination with chrysanthemum. (13) A composition for promoting collagen production, comprising chrysanthemum and Cassia obtusifolia or Polygonatum odoratum. (14) A composition according to any one of (11) to (13) for improving skin firmness. (15) A composition according to any one of (11) to (14) for use in which, when the dry weight of chrysanthemum is ca and the dry weight of cassia seed is cb, the ratio of ca / cb is 0.1 to 10. (16) A composition according to any one of (11) to (14) for use such that the ca / cd ratio is 0.1 to 10, where the dry weight of chrysanthemum is ca and the dry weight of Polygonatum odoratum is cd. (17) A composition for oral use, as described in any one of (11) to (16). (18) Use of a combination of crowberry and hibiscus or corn silk for the manufacture of drugs intended to promote collagen production. (19) Use of a combination of crowberry and hibiscus or corn silk for the manufacture of drugs intended to promote the production of PDGF-bb. (20) The use described in (18) or (19) for the manufacture of a drug intended to improve skin firmness. (21) Use as described in any of (18) to (20) to use such that CA / CB is 0.1 to 10, where CA is the dry weight of the black crowberry and CB is the dry weight of the hibiscus. (22) Use as described in any of (18) to (20) to use such that CA / CD is 0.1 to 10, where CA is the dry weight of the black crowberry and CD is the dry weight of the corn silk. (23) The use according to any one of (18) to (22), wherein the drug is in the form of an oral composition. (24) Use of a combination of chrysanthemum and Cassia obtusifolia or Polygonatum odoratum for the manufacture of a drug intended to promote collagen production. (25) Use according to (24) for the manufacture of a medicament for improving muscle firmness. (26) Use according to (24) or (25) such that when the dry weight of chrysanthemum is ca and the dry weight of valerian is cb, ca / cb is 0.1 to 10. (27) Use according to (24) or (25) such that when the dry weight of chrysanthemum is ca and the dry weight of water dropwort is cd, ca / cd is 0.1 to 10. (28) Use according to any one of (24) to (27) where the medicament is in the form of an oral composition. (29) Use of a combination of black mulberry and hibiscus or corn silk for promoting the production of collagen. (30) Use of a combination of black mulberry and hibiscus or corn silk for promoting the production of PDGF-bb. (31) Use according to (29) or (30) for improving muscle firmness. (32) Use according to any one of (29) to (31) such that when the dry weight of black mulberry is CA and the dry weight of hibiscus is CB, CA / CB is 0.1 to 10. (33) Use according to any one of (29) to (31) such that when the dry weight of black mulberry is CA and the dry weight of corn silk is CD, CA / CD is 0.1 to 10. (34) Use according to any one of (29) to (33) where black mulberry, hibiscus, or corn silk is in the form of an oral composition. (35) Use of a combination of chrysanthemum and valerian or water dropwort for promoting the production of collagen. (36) Use according to (35) for improving muscle firmness. (37) Use according to (35) or (36) such that when the dry weight of chrysanthemum is ca and the dry weight of valerian is cb, ca / cb is 0.1 to 10. When the dry weight of chrysanthemum is ca and the dry weight of lily bulb is cd, the use described in (35) or (36) for use such that ca / cd is 0.1 to 10. (39) The use according to any one of (35) to (38), wherein chrysanthemum, safflower, or lily bulb is in the form of an oral composition. (40) A combination of white mulberry and hibiscus or corn silk for promoting the production of collagen. (41) A combination of white mulberry and hibiscus or corn silk for promoting the production of PDGF-bb. (42) The combination according to (40) or (41) for improving skin firmness. (43) The combination according to any one of (40) to (42) for use such that when the dry weight of white mulberry is CA and the dry weight of hibiscus is CB, CA / CB is 0.1 to 10. (44) The combination according to any one of (40) to (42) for use such that when the dry weight of white mulberry is CA and the dry weight of corn silk is CD, CA / CD is 0.1 to 10. (45) The combination according to any one of (40) to (44), wherein white mulberry, hibiscus, or corn silk is in the form of an oral composition. (46) A combination of chrysanthemum and safflower or lily bulb for promoting the production of collagen. (47) The combination according to (46) for improving skin firmness. (48) The combination according to (46) or (47) for use such that when the dry weight of chrysanthemum is ca and the dry weight of safflower is cb, ca / cb is 0.1 to 10. (49) The combination according to (46) or (47) for use such that when the dry weight of chrysanthemum is ca and the dry weight of lily bulb is cd, ca / cd is 0.1 to 10. (50) The combination according to any one of (46) to (49), wherein chrysanthemum, safflower, or lily bulb is in the form of an oral composition. (51) A method for promoting collagen production in a subject, comprising administering an effective amount of a combination of crowberry and hibiscus or corn silk. (52) A method for promoting the production of PDGF-bb in a subject, comprising administering an effective amount of a combination of crowberry and hibiscus or corn silk. (53) The method according to (51) or (52), which is a method for improving skin firmness in a subject. (54) The method according to any of (51) to (53) for administering so that the CA / CB ratio is 0.1 to 10, where CA is the dry weight of the black crowberry and CB is the dry weight of the hibiscus. (55) A method according to any of (51) to (53) for administering so that the CA / CD ratio is 0.1 to 10, where CA is the dry weight of the black soybean and CD is the dry weight of the corn silk. (56) The method according to any one of (51) to (55), wherein the form of the oral composition is crowberry, hibiscus, or corn silk. (57) A method for promoting collagen production in a subject, comprising administering an effective amount of a combination of chrysanthemum and Cassia seed or Polygonatum odoratum. (58) The method described in (57), which is a method for improving skin firmness in a subject. (59) The method according to (57) or (58) for using ca / cb such that the ratio is 0.1 to 10, where ca is the dry weight of chrysanthemum and cb is the dry weight of cassia seed. (60) The method according to (57) or (58) for using ca / cd such that the dry weight of chrysanthemum is 0.1 to 10, where ca is the dry weight of chrysanthemum and cd is the dry weight of Polygonatum odoratum. (61) The method according to any one of (57) to (60), wherein the chrysanthemum, Cassia seed, or Polygonatum odoratum is in the form of an oral composition.

[0013] According to the present invention, a combination for promoting protein production is provided. By using the combination of the present invention, it is possible to effectively promote protein production. [Brief explanation of the drawing]

[0014] [Figure 1] Figure 1 is a graph evaluating the collagen production-promoting effect of crowberry and / or hibiscus. [Figure 2] Figure 2 is a graph evaluating the collagen production-promoting effects of crowberry and / or corn silk. [Figure 3] Figure 3 is a graph evaluating the collagen production-promoting effect of chrysanthemum and / or Cassia seed. [Figure 4] Figure 4 is a graph evaluating the collagen production-promoting effect of chrysanthemums and / or Polygonatum odoratum. [Figure 5] Figure 5 is a graph evaluating the effect of black crowberry and / or hibiscus on promoting PDGF-bb production. [Figure 6] Figure 6 is a graph evaluating the effect of black crowberry and / or corn silk on promoting PDGF-bb production. [Figure 7] Figure 7 is a graph evaluating the improvement effects of crowberry and / or hibiscus on skin dryness and other related issues. [Figure 8] Figure 8 is a graph evaluating the effects of black crowberry and / or hibiscus on improving skin firmness and other related factors. [Figure 9] Figure 9 is a graph evaluating the effects of crowberry and / or corn silk on improving skin texture and other aspects. [Figure 10] Figure 10 is a graph evaluating the effects of chrysanthemum and / or cassia on improving skin moisture, etc. [Figure 11] Figure 11 is a graph evaluating the effects of chrysanthemums and / or Cassia obtusifolia on improving skin firmness and other related issues. Detailed description of the invention

[0015] The present invention provides a combination for promoting protein production. Examples of such combinations include combinations of food components, and such combinations of food components may be combinations of food components or methods for combining food components.

[0016] According to one embodiment of the present invention, a collagen production promoter comprising crowberry is provided for use in combination with hibiscus or a composition comprising hibiscus. Such a collagen production promoter comprising crowberry may also be a composition comprising crowberry for promoting collagen production. Such promotion of collagen production may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

[0017] According to another embodiment of the present invention, a collagen production promoter comprising hibiscus is provided for use in combination with crowberry or a composition comprising crowberry. Such a hibiscus-containing collagen production promoter may be a hibiscus-containing composition for promoting collagen production. Such promotion of collagen production may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

[0018] According to another embodiment of the present invention, a collagen production promoter comprising crowberry and hibiscus is provided. Such a collagen production promoter comprising crowberry and hibiscus may be a composition comprising crowberry and hibiscus for promoting collagen production. Such promotion of collagen production may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

[0019] According to another embodiment of the present invention, a PDGF-bb production promoter comprising crowberry is provided for use in combination with hibiscus or a composition comprising hibiscus. Such a crowberry-containing PDGF-bb production promoter may also be a composition comprising crowberry for promoting the production of PDGF-bb. Such promotion of PDGF-bb production may be achieved by promoting collagen production or not.

[0020] According to another embodiment of the present invention, a PDGF-bb production promoter comprising hibiscus is provided for use in combination with crowberry or a composition comprising crowberry. Such a hibiscus-containing PDGF-bb production promoter may be a hibiscus-containing composition for promoting the production of PDGF-bb. Such promotion of PDGF-bb production may be achieved by promoting collagen production or not.

[0021] According to another embodiment of the present invention, a PDGF-bb production promoter comprising crowberry and hibiscus is provided. Such a PDGF-bb production promoter comprising crowberry and hibiscus may be a composition comprising crowberry and hibiscus for promoting the production of PDGF-bb. Such promotion of PDGF-bb production may be achieved by promoting collagen production or not.

[0022] According to another embodiment of the present invention, the following conditions are addressed on the face: dryness and roughness of the skin, roughness of the skin, moisture of the skin, smoothness and smoothness of the skin, radiance of the skin, skin texture, transparency of the skin, brightness of the skin, dullness of the skin, yellowness of the skin, redness of the skin, darkness of the skin, uneven skin tone, poor complexion, skin glow, forehead wrinkles, wrinkles around the mouth, crow's feet and fine lines, prominence of nasolabial folds, firmness and elasticity of the skin, softness of the skin, sagging of the cheeks, sagging under the eyes, sagging of the face line, ease of leaving marks from pillows and sheets, prominence of blemishes and freckles, darkness of blemishes and freckles, number of blemishes and freckles, size of blemishes, dark circles under the eyes, darkening under and around the eyes, enlarged pores, blackheads, skin color, darkening around the mouth, chapped lips, blood circulation after washing the face. Skin dryness, itchy skin, aged appearance, oily / greasy skin, acne proneness, noticeable acne scars, makeup application, eye opening (e.g., wide-open eyes), overall skin condition, skin appearance / beauty, or facial appearance; dryness / roughness of hands, arms, and legs, skin moisture, roughness of knees and heels, skin radiance, skin texture, skin firmness, skin wrinkles, skin sagging, skin complexion, skin brightness, skin glow, yellowish skin tone, itchy skin, oily / greasy skin, skin transparency, split nails / nail breakage, hand condition, neck wrinkles, skin water repellency, overall hand and arm condition, or overall skin condition of the entire body; hair firmness / body, hair shine, scalp itchiness, hair loss, gray hair, hair growth rate, or hair smoothness;A combination of black crowberry and hibiscus is offered to prevent or improve other symptoms or conditions such as fatigue, difficulty recovering from fatigue, joint pain / back pain, feeling well-rested upon waking / waking up, difficulty falling asleep, feeling heavy and sluggish, digestive issues, susceptibility to hangovers, facial swelling, leg swelling, susceptibility to muscle pain, stiff shoulders, cold extremities (cold hands and feet, etc.), receding gums, hot flashes, mood swings / irritability, eye strain, overall physical condition, or lack of energy, and is preferred. A combination of crowberry and hibiscus is provided for improving one or more of the following: dry skin, rough skin, skin moisture, skin smoothness, skin radiance, skin texture, forehead wrinkles, wrinkles around the mouth, skin firmness, skin softness, cheek sagging, under-eye sagging, jawline sagging, susceptibility to pillow and sheet marks, overall skin condition, and skin appearance / beauty. More preferably, a combination of crowberry and hibiscus is provided for improving skin firmness.

[0023] This combination may be a hibiscus-containing preventive or ameliorative agent for the above symptoms, for use in combination with crowberry or a composition containing crowberry, and such a hibiscus-containing preventive or ameliorative agent for the above symptoms may be a hibiscus-containing composition for the prevention or amelioration of the above symptoms. Furthermore, this combination may be a crowberry-containing preventive or ameliorative agent for the above symptoms, for use in combination with hibiscus or a composition containing hibiscus, and such a crowberry-containing preventive or ameliorative agent for the above symptoms may be a crowberry-containing composition for the prevention or amelioration of the above symptoms. In addition, this combination may be a crowberry-containing and hibiscus-containing preventive or ameliorative agent for the above symptoms, and such a crowberry-containing and hibiscus-containing preventive or ameliorative agent for the above symptoms may be a crowberry-containing and hibiscus composition for the prevention or amelioration of the above symptoms. Such prevention or amelioration of the above symptoms may be achieved by promoting collagen production or not. Furthermore, the prevention or improvement of the above-mentioned symptoms may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

[0024] According to another embodiment of the present invention, a collagen production promoter comprising crowberry is provided for use in combination with corn silk or a composition comprising corn silk. Such a crowberry-containing collagen production promoter may also be a composition comprising crowberry for promoting collagen production. Such promotion of collagen production may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

[0025] According to another embodiment of the present invention, a collagen production promoter comprising corn silk is provided for use in combination with crowberry or a composition comprising crowberry. Such a collagen production promoter comprising corn silk may also be a composition comprising corn silk for promoting collagen production. Such promotion of collagen production may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

[0026] According to another embodiment of the present invention, a collagen production promoter comprising crowberry and corn silk is provided. Such a collagen production promoter comprising crowberry and corn silk may be a composition comprising crowberry and corn silk for promoting collagen production. Such promotion of collagen production may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

[0027] According to another embodiment of the present invention, a PDGF-bb production promoter comprising crowberry is provided for use in combination with corn silk or a composition comprising corn silk. Such a crowberry-containing PDGF-bb production promoter may also be a composition comprising crowberry for promoting the production of PDGF-bb. Such promotion of PDGF-bb production may be achieved by promoting collagen production or not.

[0028] According to another embodiment of the present invention, a PDGF-bb production promoter comprising corn silk is provided for use in combination with crowberry or a composition comprising crowberry. Such a PDGF-bb production promoter comprising corn silk may also be a composition comprising corn silk for promoting the production of PDGF-bb. Such promotion of PDGF-bb production may be achieved by promoting collagen production or not.

[0029] According to another embodiment of the present invention, a PDGF-bb production promoter comprising crowberry and corn silk is provided. Such a PDGF-bb production promoter comprising crowberry and corn silk may be a composition comprising crowberry and corn silk for promoting the production of PDGF-bb. Such promotion of PDGF-bb production may be achieved by promoting collagen production or not.

[0030] According to another embodiment of the present invention, the following conditions are addressed on the face: dryness and roughness of the skin, roughness of the skin, moisture of the skin, smoothness and smoothness of the skin, radiance of the skin, skin texture, transparency of the skin, brightness of the skin, dullness of the skin, yellowness of the skin, redness of the skin, darkness of the skin, uneven skin tone, poor complexion, skin glow, forehead wrinkles, wrinkles around the mouth, crow's feet and fine lines, prominence of nasolabial folds, firmness and elasticity of the skin, softness of the skin, sagging of the cheeks, sagging under the eyes, sagging of the face line, ease of leaving marks from pillows and sheets, prominence of blemishes and freckles, darkness of blemishes and freckles, number of blemishes and freckles, size of blemishes, dark circles under the eyes, darkening under and around the eyes, enlarged pores, blackheads, skin color, darkening around the mouth, chapped lips, blood circulation after washing the face. Skin dryness, itchy skin, aged appearance, oily / greasy skin, acne proneness, noticeable acne scars, makeup application, eye opening (e.g., wide-open eyes), overall skin condition, skin appearance / beauty, or facial appearance; dryness / roughness of hands, arms, and legs, skin moisture, roughness of knees and heels, skin radiance, skin texture, skin firmness, skin wrinkles, skin sagging, skin complexion, skin brightness, skin glow, yellowish skin tone, itchy skin, oily / greasy skin, skin transparency, split nails / nail breakage, hand condition, neck wrinkles, skin water repellency, overall hand and arm condition, or overall skin condition of the entire body; hair firmness / body, hair shine, scalp itchiness, hair loss, gray hair, hair growth rate, or hair smoothness;A combination of crowberry and corn silk is provided for the prevention or improvement of other symptoms or conditions, such as fatigue, ease of recovery from fatigue, joint pain / lower back pain, feeling of deep sleep upon waking / waking up, difficulty falling asleep, feeling heavy and sluggish in the body, digestive issues, susceptibility to hangovers, facial swelling, leg swelling, susceptibility to muscle pain, stiff shoulders, cold extremities (cold hands and feet, etc.), receding gums, hot flashes / flushing, mood swings / irritability, eye strain, overall physical condition, or sense of energy in the body. Preferably, a combination of crowberry and corn silk is provided for the improvement of one or more conditions selected from the group consisting of skin texture, wrinkles around the mouth, prominent nasolabial folds, sagging cheeks, sagging under the eyes, sagging of the face line, susceptibility to pillow and sheet marks, and skin appearance. More preferably, a combination of crowberry and corn silk is provided for the improvement of sagging cheeks.

[0031] This combination may be a preventive or ameliorative agent for the above symptoms comprising corn silk for use in combination with crowberry or a composition comprising crowberry, and such a preventive or ameliorative agent for the above symptoms comprising corn silk may be a composition comprising corn silk for the prevention or amelioration of the above symptoms. Furthermore, this combination may be a preventive or ameliorative agent for the above symptoms comprising crowberry for use in combination with corn silk or a composition comprising corn silk, and such a preventive or ameliorative agent for the above symptoms comprising crowberry may be a composition comprising crowberry for the prevention or amelioration of the above symptoms. In addition, this combination may be a preventive or ameliorative agent for the above symptoms comprising crowberry and corn silk, and such a preventive or ameliorative agent for the above symptoms comprising crowberry and corn silk may be a composition comprising crowberry and corn silk for the prevention or amelioration of the above symptoms. Such prevention or amelioration of the above symptoms may be achieved by promoting collagen production or not. Furthermore, the prevention or improvement of the above-mentioned symptoms may be achieved by promoting the production of PDGF-bb, or it may be achieved without promoting the production of PDGF-bb.

[0032] According to another embodiment of the present invention, a chrysanthemum-containing collagen production promoter is provided for use in combination with Cassia seed or a composition comprising Cassia seed. Such a chrysanthemum-containing collagen production promoter may also be a chrysanthemum-containing composition for promoting collagen production.

[0033] According to another embodiment of the present invention, a collagen production promoter comprising Cassia obtusifolia is provided for use in combination with chrysanthemum or a composition comprising chrysanthemum. Such a collagen production promoter comprising Cassia obtusifolia may be a composition comprising Cassia obtusifolia for promoting collagen production.

[0034] According to another embodiment of the present invention, a collagen production promoter comprising chrysanthemum and cassia seed is provided. Such a collagen production promoter comprising chrysanthemum and cassia seed may be a composition comprising chrysanthemum and cassia seed for promoting collagen production.

[0035] According to another embodiment of the present invention, the following conditions are addressed on the face: dryness and roughness of the skin, roughness of the skin, moisture of the skin, smoothness and suppleness of the skin, luster of the skin, texture of the skin, transparency of the skin, brightness of the skin, dullness of the skin, yellowness of the skin, redness of the skin, darkness of the skin, uneven skin tone, poor complexion, skin radiance, forehead wrinkles, crow's feet and fine lines, prominence of nasolabial folds, firmness and elasticity of the skin, softness of the skin, sagging of the cheeks, sagging under the eyes, sagging of the face line, ease of leaving marks from pillows and sheets, prominence of blemishes and freckles, darkness of blemishes and freckles, number of blemishes and freckles, size of blemishes, under the eyes. Dark circles under the eyes, dark spots around the eyes, enlarged pores, blackheads, skin complexion, dark spots around the mouth, chapped lips, lip color, tightness after washing face, itchy skin, aged appearance, oily / greasy skin, proneness to acne, noticeable acne scars, makeup application, eye opening (wide open, etc.), overall skin condition or facial impression; dryness / roughness of hands, arms, legs, etc., skin moisture, rough knees and heels, skin radiance, skin texture, skin firmness, skin wrinkles, skin sagging, skin complexion, skin brightness, skin glow, yellowish skin tone, itchy skin, oily / greasy skin, skin transparency Light sensitivity, brittle or split nails, rough hands, neck wrinkles, skin's water-repellent properties, overall condition of hands and arms, or overall condition of the skin on the whole body; hair strength and body, hair shine, scalp itchiness, hair loss, gray hair, hair growth rate, or hair smoothness; or other symptoms or conditions such as ease of recovery from fatigue, joint pain or back pain, feeling of deep sleep upon waking, difficulty falling asleep, feeling heavy and sluggish, digestive issues, susceptibility to hangovers, facial swelling, leg swelling, susceptibility to muscle pain, stiff shoulders, cold extremities (cold hands and feet, etc.), receding gums, hot flashes, or low mood. A combination of chrysanthemum and cassia is provided for the prevention or improvement of irritability, eye fatigue, overall physical condition, or physical energy level. Preferably, a combination of chrysanthemum and cassia is provided for the improvement of one or more of the following: skin moisture, skin luster, skin texture, skin wrinkles, neck wrinkles, skin firmness, cheek sagging, face line sagging, susceptibility to pillow and sheet marks, skin water repellency, aging face, and facial appearance / beauty. More preferably, a combination of chrysanthemum and cassia is provided for the improvement of skin firmness.

[0036] This combination may be a preventive or ameliorative agent for the above symptoms comprising Cassia obtusifolia for use in combination with chrysanthemum or a composition comprising chrysanthemum, and such a preventive or ameliorative agent for the above symptoms comprising Cassia obtusifolia may be a composition comprising Cassia obtusifolia for the prevention or improvement of the above symptoms. Furthermore, this combination may be a preventive or ameliorative agent for the above symptoms comprising chrysanthemum or a composition comprising Cassia obtusifolia for use in combination with chrysanthemum, and such a preventive or ameliorative agent for the above symptoms comprising chrysanthemum may be a composition comprising chrysanthemum for the prevention or improvement of the above symptoms. In addition, this combination may be a preventive or ameliorative agent for the above symptoms comprising chrysanthemum and Cassia obtusifolia, and such a preventive or ameliorative agent for the above symptoms comprising chrysanthemum and Cassia obtusifolia may be a composition comprising chrysanthemum and Cassia obtusifolia for the prevention or improvement of the above symptoms. Such prevention or improvement of the above symptoms may be achieved by promoting collagen production or not.

[0037] According to another embodiment of the present invention, a collagen production promoter comprising chrysanthemum is provided for use in combination with Polygonatum odoratum or a composition comprising Polygonatum odoratum. Such a collagen production promoter comprising chrysanthemum may be a composition comprising chrysanthemum for promoting collagen production.

[0038] According to another embodiment of the present invention, a collagen production promoter comprising Polygonatum odoratum is provided for use in combination with chrysanthemum or a composition comprising chrysanthemum. Such a collagen production promoter comprising Polygonatum odoratum may be a composition comprising Polygonatum odoratum for promoting collagen production.

[0039] According to another embodiment of the present invention, a collagen production promoter comprising chrysanthemum and Solomon's seal is provided. Such a collagen production promoter comprising chrysanthemum and Solomon's seal may be a composition comprising chrysanthemum and Solomon's seal for promoting collagen production.

[0040] According to another embodiment of the present invention, the following are addressed on the face: dryness and roughness of the skin, roughness of the skin, moisture of the skin, smoothness and suppleness of the skin, radiance of the skin, skin transparency, skin brightness, dullness of the skin, yellowness of the skin, redness of the skin, darkness of the skin, uneven skin tone, poor complexion, skin glow, forehead wrinkles, crow's feet and fine lines, prominent nasolabial folds, firmness and elasticity of the skin, softness of the skin, sagging cheeks, sagging under the eyes, sagging of the face line, ease of leaving marks from pillows and sheets, and the prominence of blemishes and freckles. The intensity of blemishes and freckles, the number of blemishes and freckles, the size of blemishes, dark circles under the eyes, dark spots under and around the eyes, enlarged pores, blackheads in pores, skin complexion, dark spots around the mouth, chapped lips, lip complexion, tightness after washing face, itchy skin, aged appearance, oily / greasy skin, susceptibility to acne, noticeable acne scars, makeup application, eye opening (wide open, etc.), overall skin condition, or facial impression; dryness / roughness of hands, arms, legs, etc., skin moisture, roughness of knees and heels, skin radiance, skin Skin texture, skin firmness, skin wrinkles, skin sagging, skin complexion, skin brightness, skin radiance, skin yellowness, skin itchiness, skin oiliness / greasiness, skin clarity, nail splitting / breakage, hand condition, neck wrinkles, skin water repellency, overall hand / arm condition, or overall skin condition of the entire body; hair strength / resilience, hair shine, scalp itchiness, hair loss, gray hair, hair growth rate, or hair smoothness; or other symptoms or conditions such as fatigue, ease of recovery from fatigue, joint pain. A combination of chrysanthemum and Polygonatum is provided for the prevention or improvement of lower back pain, feeling well-rested upon waking, difficulty falling asleep, feeling heavy and sluggish, digestive issues, susceptibility to hangovers, facial swelling, leg swelling, susceptibility to muscle pain, stiff shoulders, poor circulation (cold hands and feet, etc.), receding gums, hot flashes, mood swings / irritability, eye strain, overall physical condition, or sense of energy in the body, and preferably a combination of chrysanthemum and Polygonatum is provided for the improvement of skin firmness.

[0041] This combination may be a preventive or ameliorative agent for the above symptoms comprising Polygonatum odoratum for use in combination with chrysanthemum or a composition comprising chrysanthemum, and such a preventive or ameliorative agent for the above symptoms comprising Polygonatum odoratum may be a composition comprising Polygonatum odoratum for the prevention or amelioration of the above symptoms. Furthermore, this combination may be a preventive or ameliorative agent for the above symptoms comprising chrysanthemum or a composition comprising Polygonatum odoratum for use in combination with chrysanthemum, and such a preventive or ameliorative agent for the above symptoms comprising chrysanthemum, may be a composition comprising chrysanthemum, may be for the prevention or amelioration of the above symptoms. In addition, this combination may be a preventive or ameliorative agent for the above symptoms comprising chrysanthemum and Polygonatum odoratum, and such a preventive or ameliorative agent for the above symptoms comprising chrysanthemum and Polygonatum odoratum may be a composition comprising chrysanthemum and Polygonatum odoratum for the prevention or amelioration of the above symptoms. Such prevention or amelioration of the above symptoms may be achieved by promoting collagen production or not.

[0042] The combination of the present invention can be applied to, but is not limited to, humans, primates including chimpanzees, pet animals such as dogs and cats, domesticated animals such as cattle, horses, sheep and goats, and mammals such as mice and rats. Humans are preferred as the target of the combination of the present invention.

[0043] The collagen used in this invention is not particularly limited, but is preferably type I collagen.

[0044] In this invention, the collagen production-promoting effect refers to the effect of improving the production of collagen protein. For example, by promoting collagen production and maintaining the amount of collagen, it is possible to exert various effects by suppressing the decrease of collagen fibers, which are the main matrix components of the dermis. The collagen production-promoting effect in this invention may be evaluated, for example, by measuring the amount of collagen to determine the amount of protein. This measurement can be carried out using antibodies specific to collagen and by various methods well known in the field, such as immunohistochemical staining using fluorescent substances, dyes, enzymes, etc., Western blotting, immunoassay methods, such as ELISA and RIA.

[0045] In this invention, the PDGF-bb production-promoting effect refers to the effect of improving the production of platelet-derived growth factor-bb (PDGF-bb) protein. For example, the promoted production of PDGF-bb acts on mesenchymal stem cells, and as a result stabilizes the mesenchymal stem cells, thereby exerting various effects. The PDGF-bb production-promoting effect in this invention may be evaluated, for example, by measuring the amount of PDGF-bb to determine the protein amount. This measurement can be carried out using antibodies specific to PDGF-bb and by various methods well known in the field, such as immunohistochemical staining using fluorescent substances, dyes, enzymes, etc., Western blotting, immunoassay methods, such as ELISA and RIA. Alternatively, it may be determined indirectly by, for example, extracting total RNA from mesenchymal stem cells and measuring the amount of mRNA encoding PDGF-bb, but measuring the actual protein amount allows for a more direct evaluation.

[0046] In this invention, "black blueberry" refers to "Vaccinium uliginosum," a plant belonging to the genus Vaccinium in the family Ericaceae. It is also commonly known as bog bilberry or great bilberry, and in Japan, it is sometimes called Asama grape or Kozan (high mountain) grape. Either the whole plant or a part of it can be used, but preferably the fruit is used. The juice derived from this black blueberry fruit is sometimes written as Wild blueberry juice concentrate (Vaccinium uliginosum) in English, and in Chinese, It is sometimes referred to as JPEG2026056591000001.jpg674. According to one embodiment of the present invention, "black crowberry" is black crowberry juice produced using all or part of a black crowberry plant, which can be produced by known methods such as fruit juicing and concentration.

[0047] In this invention, "hibiscus" refers to Hibiscus sabdariffa or Hibiscus rosa-sinensis (Chinese name: Luoshenhua), a plant belonging to the genus Hibiscus in the Malvaceae family, also known as roselle and hibiscus, respectively. Generally, hibiscus is a plant native to Africa and, due to its refreshing tartness, is used as a sauce in French and Italian cuisine, as well as a herb. In this invention, any common hibiscus can be used, but roselle is preferred. Any part of the plant can be used, either whole or in part, and is not limited to these parts. For example, flowers, calyx, buds, fruits, pericarp, seeds, seed coats, stems, leaves, branches, branch leaves, trunk, bark, roots, rhizomes, root bark, etc., and calyx and / or flowers are preferred. In this invention, "hibiscus" can be used fresh, dried, or extracted with a solvent. According to one embodiment of the present invention, "hibiscus" refers to a hibiscus extract prepared using all or part of a hibiscus plant.

[0048] In this invention, "corn silk" refers to the dried style and stigma of the female flower of corn (Zea mays L.), a member of the grass family (Gramineae), and is sometimes known as Nanbanmo or Nanba no Mou, a herbal medicine. In China, it is sometimes used under the names "Yushushu Zhutou," "Yushushu Rui," or "Yumi Zhu," and in Japan, it is sometimes sold commercially under the names "Nanba no Mou" or "Nanbanmo." The style and stigma of the female flower of corn may be plucked off and dried. The drying method is not limited to these, but examples include hot air drying, vacuum freeze-drying, far-infrared drying, microwave heating drying, and sun-drying. The corn (Zea mays L.) of the grass family mentioned above may be a closely related species or a cultivated variety. According to one embodiment of this invention, "corn silk" is a dried corn silk powder produced using all or part of corn silk, and this dried powder may be used as is or extracted before use.

[0049] In this invention, "chrysanthemum" refers to "Chrysanthemum morifolium Ramat," a plant belonging to the genus Chrysanthemum in the family Asteraceae. The "chrysanthemum" in this invention is native to Japan, readily available, and its flowers have been used medicinally in China since ancient times. In Japan, it is consumed as tea or alcohol, and used in cooking, and is said to be effective for dizziness, headaches, and eye strain. Specific varieties of "chrysanthemum" in this invention include purple chrysanthemums known as "Enmeiraku," yellow chrysanthemums known as "Abokyu," and "small chrysanthemums," with purple chrysanthemums being preferred. Any part of the plant, either the whole or a part thereof, can be used, such as stems, leaves, fruits, pericarps, seeds, seed coats, roots, and flowers, with flowers being preferred. Fresh or processed (e.g., dried powder) parts can be used as needed. According to one embodiment of this invention, "chrysanthemum" refers to dried chrysanthemum powder produced using the whole or a part of a chrysanthemum plant. This dried powder may be used as is or extracted before use.

[0050] In this invention, "Ketsumeishi" refers to the dried seeds of Senna obtusifolia or Cassia tora L., which are plants belonging to the Caesalpinioideae subfamily of the Fabaceae family. While not limited to these, mature seeds are preferred. According to one embodiment of this invention, "Ketsumeishi" refers to a Ketsumeishi extract produced using all or part of a Ketsumeishi plant.

[0051] In this invention, "Polygonatum falcatum" refers to "Polygonatum falcatum," a perennial herb belonging to the genus Polygonatum in the family Liliaceae. While the whole or a part of the plant can be used, the rhizome is preferred, and it can be used fresh or processed (e.g., dried powder) as needed. According to one embodiment of this invention, "Polygonatum falcatum" refers to dried powder produced using the whole or a part of the plant, and this dried powder may be used as is or extracted before use.

[0052] The method for producing the extract in the present invention is not particularly limited and can be carried out according to methods commonly used in the art. For example, it may be carried out by extracting raw materials such as crowberry, corn silk, hibiscus, chrysanthemum, cassia seed, and Polygonatum odoratum. The extraction method is not limited, but examples include hot water extraction, ultrasonic extraction, filtration, reflux extraction, and solvent extraction. These may be carried out individually or in combination of two or more methods. Furthermore, to obtain a high-purity extract, the extract may be extracted one or more times using the same method.

[0053] The type of solvent used for producing the extract in the present invention is not particularly limited, and any solvent known in the art may be used as long as it yields an extract having the desired effect of the present invention. Examples of such solvents, though not limited to them, include water, hexane, ether, ethyl acetate, butanol, acetone, propanol, ethanol, methanol, propylene glycol, 1,3-butylene glycol, and more than two of these may be used in combination.

[0054] If black crowberry, corn silk, hibiscus, chrysanthemum, Cassia seed, or Polygonatum odoratum (including fruit juice, dried or extracted forms) are commercially available, they may be used if they provide the desired effects of the present invention.

[0055] The daily intake of crowberry in this invention is not particularly limited, but is preferably 28.3 mg to 255 mg, more preferably 42.5 mg to 170 mg, by dry weight. The crowberry content in the composition of this invention may be adjusted as appropriate according to the dosage and administration. For example, the composition may be adjusted so that it contains the full amount, half, or one-third of the daily intake of crowberry in a total composition of 100 mg to 1000 mg. Intake of crowberry in this invention is preferably by oral administration.

[0056] The daily intake of hibiscus in the present invention is not particularly limited, but is preferably 40 mg to 360 mg, more preferably 60 mg to 240 mg, by dry weight. The hibiscus content in the composition of the present invention may be adjusted as appropriate according to the dosage and administration. For example, the composition may be adjusted so that it contains the full amount, half the amount, or one-third of the daily intake of hibiscus in a total composition of 100 mg to 1000 mg. The intake of hibiscus in the present invention is preferably by oral ingestion.

[0057] The daily intake of corn silk in the present invention is not particularly limited, but is preferably 33.3 mg to 300 mg, more preferably 50 mg to 200 mg, by dry weight. The corn silk content in the composition of the present invention may be adjusted as appropriate according to the dosage and administration method. For example, the composition may be adjusted so that it contains the full amount, half the amount, or one-third of the daily intake amount of corn silk in a total composition of 100 mg to 1000 mg. The intake of corn silk in the present invention is preferably by oral administration.

[0058] The daily intake of chrysanthemum in this invention is not particularly limited, but is preferably 8.3 mg to 75 mg, more preferably 12.5 mg to 50 mg, by dry weight. The chrysanthemum content in the composition of this invention may be adjusted as appropriate according to the dosage and administration. For example, the composition may be adjusted so that it contains the full amount, half, or one-third of the daily intake of chrysanthemum in a total composition of 100 mg to 1000 mg. Chrysanthemum in this invention is preferably taken orally.

[0059] The daily intake of Cassia seed in this invention is not particularly limited, but is preferably 16.7 mg to 150 mg, more preferably 25 mg to 100 mg, by dry weight. The content of Cassia seed in the composition of this invention may be adjusted as appropriate according to the dosage and administration. For example, the composition may be adjusted so that it contains the full amount, half the amount, or one-third of the daily intake of Cassia seed in a total composition of 100 mg to 1000 mg. The intake of Cassia seed in this invention is preferably by oral administration.

[0060] The daily intake of Polygonatum odoratum in this invention is not particularly limited, but is preferably 83.3 mg to 750 mg, more preferably 125 mg to 500 mg, by dry weight. The amount of Polygonatum odoratum in the composition of this invention may be adjusted as appropriate according to the dosage and administration. For example, the composition may be adjusted so that it contains the full amount, half the amount, or one-third of the daily intake of Polygonatum odoratum in a total composition of 100 mg to 1000 mg. Ingestion of Polygonatum odoratum in this invention is preferably by oral ingestion.

[0061] The amounts of crowberry and hibiscus used in the composition of the present invention can be appropriately determined depending on the application, but preferably, when the dry weight of crowberry is CA and the dry weight of hibiscus is CB, CA / CB is 0.1 to 10, and more preferably CA / CB is 0.3 to 1.5.

[0062] The amounts of crowberry and corn silk used in the composition of the present invention can be appropriately determined depending on the application, but preferably, when the dry weight of crowberry is CA and the dry weight of corn silk is CD, CA / CD is 0.1 to 10, and more preferably CA / CD is 0.3 to 1.5.

[0063] The amounts of chrysanthemum and cassia seed used in the composition of the present invention can be appropriately determined depending on the application, but preferably, when the dry weight of chrysanthemum is ca and the dry weight of cassia seed is cb, the ca / cb ratio is 0.1 to 10, and more preferably, the ca / cb ratio is 0.3 to 1.5.

[0064] The amounts of chrysanthemum and Polygonatum used in the composition of the present invention can be appropriately determined depending on the application, but preferably, when the dry weight of chrysanthemum is ca and the dry weight of Polygonatum is cd, the ca / cd ratio is 0.1 to 10, and more preferably, the ca / cd ratio is 0.3 to 1.5.

[0065] The dry weight value in this invention is not limited, but may be obtained by directly measuring the weight of thoroughly dried crowberry, corn silk, hibiscus, chrysanthemum, Cassia obtusifolia, and Polygonatum odoratum (including fruit juice and processed products such as dried or extracted products), or it may be obtained by converting the Brix (weight of soluble solids per 100g of fruit juice or extract). The conversion from Brix to dry weight can be performed using the following formula 1.

number

[0066] According to one embodiment of the present invention, the dry weight of the crowberry is calculated using the Brix value.

[0067] The composition in the present invention may be a pharmaceutical composition, a cosmetic composition, or a food composition, although this is not limited to these. The composition in the present invention is preferably a food composition.

[0068] The composition in the present invention may be either an oral composition or a topical composition. In the present invention, crowberry, corn silk, hibiscus, chrysanthemum, cassia seed, and Solomon's seal are preferably absorbed from the gastrointestinal tract by oral ingestion, and their active ingredients act in the body. Therefore, according to one preferred embodiment of the present invention, the composition is an oral composition.

[0069] When the composition of the present invention is an oral composition, known components (additives) that are incorporated into oral compositions may be further incorporated. Such components are not particularly limited, but examples include emulsifiers, wettable powders, solvents, emollients, stabilizers, thickeners, preservatives, lubricants, chelating agents, fillers, excipients, powders, fragrances, flavorings, absorbents, dyes, opacifiers, antioxidants, preservatives, vitamins, amino acids, nutrients, minerals (electrolytes), flavorings such as synthetic and natural flavorings, pectinic acid and its salts, alginic acid and its salts, organic acids, pH adjusters, glycerin, alcohol, and carbonating agents used in carbonated beverages.

[0070] The oral composition in this invention may be a liquid, a semi-solid, or a solid.

[0071] When the composition of the present invention is used as a topical composition, known components (additives) that are incorporated into topical compositions may be further added. Such components are not limited to, but include, for example, emulsifiers, wettable powders, solvents, emollients, stabilizers, thickeners, preservatives, lubricants, chelating agents, fillers, excipients, powders, fragrances, scents, absorbents, dyes, opacifiers, antioxidants, vitamins, amino acids, and the like.

[0072] The topical composition in this invention may be a liquid, a semi-solid, or a solid. [Examples]

[0073] The present invention will be specifically described based on the following examples, but the present invention is not limited to these examples. Unless otherwise specified, the content is expressed in mass percent.

[0074] 1. Evaluation of the effects of drugs on collagen production Cell culture The cells used were commercially available human neonatal dermal fibroblasts (Cryo NHDF-Neo, Sanko Junyaku). 2 × 10⁶ cells were placed per well in a commercially available 24-well plate. 5Human neonatal dermal fibroblasts were seeded to form individual cells and cultured in a commercially available cell culture medium (D-MEM (1 g / L glucose), Wako Pure Chemical Industries) supplemented with 10% fetal bovine serum at 37°C under a 5% CO2 and saturated water vapor atmosphere until confluence was reached. After culturing until confluence, the culture medium in each well was replaced with a culture medium containing each drug, prepared in the following order: crowberry fruit juice, hibiscus flower extract, or crowberry fruit juice and hibiscus flower extract in the amounts shown in Table 2 by dry weight; crowberry fruit juice, corn silk extract, or crowberry fruit juice and corn silk extract in the amounts shown in Table 3 by dry weight; purple chrysanthemum extract, Cassia seed extract, or purple chrysanthemum extract and Cassia seed extract in the amounts shown in Table 4 by dry weight; purple chrysanthemum extract, Polygonatum odoratum extract, or purple chrysanthemum extract and Polygonatum odoratum extract in the amounts shown in Table 5 by dry weight; and the culture medium was incubated again for 72 hours. The drugs used were those listed in Table 1. In the control group, the same procedure was performed by substituting the drug-free cell culture medium (D-MEM (1 g / L glucose), Wako Pure Chemical Industries) for the drug-free medium.

[0075] Drugs applied to cells The medications used were those listed in Table 1 below. [Table 1]

[0076] Black crowberry fruit juice and hibiscus flower extract were applied to the cells in each well in the amounts shown in Table 2 below by dry weight. [Table 2]

[0077] Black crowberry fruit juice and corn silk dry powder extract were applied to the cells in each well in the amounts shown in Table 3 below. [Table 3]

[0078] Dried purple chrysanthemum powder and Cassia seed extract were applied to the cells in each well in the amounts shown in Table 4 below. [Table 4]

[0079] Dried purple chrysanthemum powder and dried Solomon's seal powder were applied to the cells in each well so that their dry weights were as shown in Table 5 below. [Table 5]

[0080] After 72 hours of incubation, the supernatant of the culture medium was collected from each well, and the concentration of the C-terminal peptide (hereinafter referred to as "PIP") of type I procollagen produced by human neonatal dermal fibroblasts in the collected supernatant was measured by ELISA using the Procollagen type I C-peptide EIA kit (Takara Bio Inc.).

[0081] Measurement of PIP concentration using ELISA method ELISA measurements were performed according to the kit manual using the following procedure. 100 μL of pre-prepared labeled antibody solution was added to each well of the plate according to the kit manual. Then, 20 μL of each concentration of pre-prepared PIP standard solution and the sample (supernatant), according to the kit manual, were added to each well using a micropipette, and the mixture was reacted at 37°C for 3 hours. The sample was added within 5 minutes of each well. The reaction mixture was discarded, and the plates were washed four times with PBS. Then, 100 μL of Substrate Solution (TMBZ) was added to each well, and the mixture was reacted at room temperature for 15 minutes. 100 μL of Stop Solution was added to each well in the order in which the Substrate Solution (TMBZ) was added to stop the reaction, and the mixture was then thoroughly mixed. The mixture was zeroed using distilled water as a control, and the absorbance was measured at a wavelength of 450 nm. The color development remained stable for up to 1 hour after reaction cessation. A standard curve was created with the concentration of each PIP standard solution on the x-axis and the corresponding absorbance on the y-axis. The PIP concentration value corresponding to the absorbance of the sample was used as the measurement result. The measurement results were corrected using the cell count in each well obtained by the Aramblue measurement to obtain the collagen production value.

[0082] The mean ± standard deviation of collagen production was calculated for each group, with n=12 per group. Multiple comparisons were performed using one-way ANOVA for comparisons between the groups. Tukey-Kramer multiple comparison tests were performed for the monotherapy group and the combination therapy group against the control group. A p-value of less than 0.05 was considered a significant increase in collagen production (* indicates p<0.05), and a p-value between 0.05 and less than 0.1 was considered a significant trend in collagen production († indicates 0.05≦p<0.1). Similarly, multiple comparison tests were performed for the combination therapy group against the monotherapy group (no symbol).

[0083] Figure 1 shows the evaluation results of collagen production by crowberry and hibiscus. Both the hibiscus-only group (Comparative Example 3) and the crowberry-and-hibiscus combined group (Example 1) showed significantly increased collagen production compared to the control group (Comparative Example 1). Furthermore, the crowberry-and-hibiscus combined group (Example 1) showed significantly increased collagen production compared to both the crowberry-only group (Comparative Example 2) and the hibiscus-only group (Comparative Example 3). In summary, the combined use of crowberry and hibiscus synergistically promotes collagen production.

[0084] Figure 2 shows the evaluation results of collagen production by black crowberry and corn silk. Both the black crowberry-only group (Comparative Example 5) and the corn silk-only group (Comparative Example 6) showed a tendency to promote collagen production more than the control group (Comparative Example 4). Furthermore, the black crowberry and corn silk combined group (Example 2) showed a significantly greater promotion of collagen production compared to the control group (Comparative Example 4). Moreover, the black crowberry and corn silk combined group (Example 2) showed a significantly greater promotion of collagen production compared to both the black crowberry-only group (Comparative Example 5) and the corn silk-only group (Comparative Example 6). From the above, it was shown that the combined use of black crowberry and corn silk synergistically promotes collagen production.

[0085] Figure 3 shows the evaluation results of collagen production by chrysanthemum and cassia seed. The group treated with both chrysanthemum and cassia seed (Example 3) showed significantly increased collagen production compared to the control group (Comparative Example 7). Furthermore, the group treated with both chrysanthemum and cassia seed (Example 3) showed significantly increased collagen production compared to both the group treated with chrysanthemum alone (Comparative Example 8) and the group treated with cassia seed alone (Comparative Example 9). Thus, it was shown that the combined use of chrysanthemum and cassia seed synergistically promotes collagen production.

[0086] Figure 4 shows the evaluation results of collagen production by chrysanthemum and Polygonatum odoratum. The group treated with chrysanthemum alone (Comparative Example 11), the group treated with Polygonatum odoratum alone (Comparative Example 12), and the group treated with both chrysanthemum and Polygonatum odoratum in combination (Example 4) all showed significantly increased collagen production compared to the control group (Comparative Example 10). Furthermore, the group treated with both chrysanthemum and Polygonatum odoratum in combination (Example 4) showed a tendency to promote collagen production more than both the group treated with chrysanthemum alone (Comparative Example 11) and the group treated with Polygonatum odoratum alone (Comparative Example 12). From the above, it was shown that the combined use of chrysanthemum and Polygonatum odoratum synergistically promotes collagen production.

[0087] 2. Evaluation of the effect of drugs on PDGF-bb production in cell culture The cells used were commercially available human umbilical vein endothelial cells (HUVEC, TAKARA). Human umbilical vein endothelial cells were seeded in commercially available 24-well plates and cultured in commercially available cell culture medium (HUVEC medium, K.A.C.) supplemented with 10% fetal bovine serum at 37°C under a 5% CO2 and saturated steam atmosphere until confluence was reached. After confluence, the medium in each well was replaced with a drug-supplemented medium containing either crowberry juice, hibiscus flower extract, or crowberry juice and hibiscus flower extract in the amounts shown in Table 6 by dry weight, or crowberry juice, corn silk extract, or crowberry juice and corn silk extract in the amounts shown in Table 7 by dry weight, and incubated again for 72 hours. The drugs used were those listed in Table 1. In the control group, the same procedure was performed by substituting the drug-free cell culture medium (HUVEC medium, manufactured by K.A.C. Co., Ltd.).

[0088] Black crowberry fruit juice and hibiscus flower extract were applied to the cells in each well in the amounts shown in Table 6 below by dry weight. [Table 6]

[0089] Black crowberry fruit juice and corn silk dry powder extract were applied to the cells in each well in the amounts shown in Table 7 below by dry weight. [Table 7]

[0090] After 72 hours of incubation, the supernatant from each well was collected, and the concentration of PDGF-bb produced by human umbilical vein endothelial cells in the collected supernatant was measured by ELISA using the commercially available EHCSRP2 kit (Thermo Fisher Scientific).

[0091] Measurement of PDGF-bb concentration by ELISA method ELISA measurements were performed according to the kit manual using the following procedure: The collected supernatant was diluted at least 5-fold with a 1× sample diluent prepared in advance according to the kit manual (the optimal dilution factor for each sample was determined as appropriate, as the level of PDGF-BB varied depending on the sample). 100 μL of each standard solution, prepared in advance according to the kit manual, was added to each well of the plate. The wells were then covered and incubated at room temperature for 2.5 hours with gentle shaking. After incubation, the solution was discarded and the plates were washed four times with a 1× wash buffer prepared in advance according to the kit manual. After washing, 100 μL of a 1× biotinylated antibody, prepared in advance according to the kit manual, was added to each well of the plate and incubated at room temperature for 1 hour with gentle shaking. After incubation, the solution was discarded again and the plates were washed four times with a 1× wash buffer. After washing, 100 μL of streptavidin-HRP solution, prepared in advance according to the kit manual, was added to each well and incubated at room temperature for 45 minutes with gentle shaking. After incubation, the solution was discarded again and washed four times with 1× wash buffer. After washing, 100 μL of TMB substrate was added to each well and incubated in the dark at room temperature for 30 minutes with gentle shaking. After incubation, 50 μL of stop solution was added to each well to stop the reaction, and then thoroughly mixed. Within 30 minutes of stopping the reaction, the absorbance of each well was measured using an ELISA plate reader set to 450 nm and 550 nm. Optical imperfections of the microplate were corrected by subtracting the 550 nm value from the 450 nm value. A standard curve was created using a 4-parameter logistic function, and the PDGF-bb concentration value corresponding to the absorbance of the measured sample was used as the measurement result. The measurement results were corrected for the dilution ratio of each sample and the cell number in each well obtained by Alamara Blue measurement to obtain the value of PDGF-bb production.

[0092] For each group, n=12, the mean ± standard deviation of PDGF-bb production was calculated. Multiple comparisons were performed using one-way ANOVA for comparisons between the groups. Tukey-Kramer multiple comparison tests were performed for the monotherapy group and the combination therapy group against the control group. A p-value of less than 0.05 was considered a significant increase in PDGF-bb production (* indicates p<0.05), and a p-value between 0.05 and less than 0.1 was considered a significant trend in PDGF-bb production († indicates 0.05≦p<0.1). Similarly, multiple comparison tests were performed for the combination therapy group against the monotherapy group (no symbol).

[0093] Figure 5 shows the evaluation results of PDGF-bb production by crowberry and hibiscus. The group treated with both crowberry and hibiscus (Example 5) showed a significant increase in PDGF-bb production compared to the control group (Comparative Example 13). Furthermore, the group treated with both crowberry and hibiscus (Example 5) showed a significant increase in PDGF-bb production compared to both the group treated with crowberry alone (Comparative Example 14) and the group treated with hibiscus alone (Comparative Example 15). Thus, the combined use of crowberry and hibiscus synergistically promotes PDGF-bb production.

[0094] Figure 6 shows the evaluation results of PDGF-bb production by black crowberry and corn silk. The group treated with black crowberry and corn silk in combination (Example 6) showed a significant increase in PDGF-bb production compared to the control group (Comparative Example 16). Furthermore, the group treated with black crowberry and corn silk in combination (Example 6) showed a significant increase in PDGF-bb production compared to both the group treated with black crowberry alone (Comparative Example 17) and the group treated with corn silk alone (Comparative Example 18). Thus, the combined use of black crowberry and corn silk was shown to synergistically promote PDGF-bb production.

[0095] Evaluation of the effects of crowberry and hibiscus on the condition of human skin, etc. A continuous use test was conducted by panelists, and the effects of the combination of crowberry and hibiscus were confirmed by the following tests. Four types of test samples were prepared and the tests were conducted in groups A to D. There were 15 panelists in group A (excipient intake group, ingested by taking two 315 mg tablets), 15 panelists in group B (ingested 170 mg (dry weight) of crowberry per day, ingested by taking two 315 mg tablets), 15 panelists in group C (ingested 240 mg (dry weight) of hibiscus per day, ingested by taking two 315 mg tablets), and 15 panelists in group D (ingested 85 mg (dry weight) of crowberry + 120 mg (dry weight) of hibiscus per day, ingested by taking two 315 mg tablets). The crowberry and hibiscus content in the tablets taken in groups B, C, and D was the same across the tablets taken in each group. The panelists were healthy Japanese women aged 35-50, excluding those who met one or more of the conditions listed in Table 8 below. [Table 8]

[0096] Each panelist took two tablets of the test sample (tablets) orally with water or lukewarm water before bedtime for 28 days. The tablets contained crowberry fruit juice as listed in Table 1 for the crowberry variety, and hibiscus flower extract as listed in Table 1 for the hibiscus variety.

[0097] Survey evaluation (Test method) A questionnaire survey was conducted regarding the condition of human skin, etc., before the start of the continuous use test and 3, 7, 14, and 28 days after the start of the continuous use test.

[0098] The questionnaire was evaluated using the VAS (Visual Analogue Scale), a commonly used evaluation scale. Specifically, on each survey day, participants were given a sheet of paper with a 10cm horizontal line drawn on it. The left end of the line was designated as the "worst condition" and the right end as the "best condition," and participants were asked to mark their perceived degree of condition on the line (by marking one point on the line segment). The distance moved to the right (or left) from the starting position of the test was used as the scale value for evaluation. The results for "skin dryness," "skin roughness," "skin moisture," "skin smoothness," "skin radiance," "skin texture," "forehead wrinkles," and "wrinkles around the mouth" are shown in Figure 7, and the results for "skin firmness," "skin softness," "cheek sagging," "under-eye sagging," "face line sagging," "ease of leaving pillow or sheet marks," "overall skin condition," and "skin impression / perceived beauty" are shown in Figure 8. In Figures 7 and 8, the control group shows the evaluation results for Group A, the black crowberry group shows the evaluation results for Group B, the hibiscus group shows the evaluation results for Group C, and the black crowberry + hibiscus group shows the evaluation results for Group D.

[0099] The results in Figures 7 and 8 show that, in particular, at 7, 14, and 28 days after the start of the continuous use test, Group D showed improvement in all evaluation items compared to Groups A, B, and C.

[0100] Furthermore, statistical analysis was performed on these results. The statistical analysis was carried out using the Tukey-Kramer method as a multiple comparison test, determining whether or not there was a significant improvement compared to the group being compared. A value of + was used when p<0.10, * when p<0.05, and ** when p<0.01. The results are shown in Table 9. In Table 9, the control is Group A, crowberry is Group B, hibiscus is Group C, and crowberry + hibiscus is Group D.

[0101] [Table 9]

[0102] Evaluation of the effects of crowberry and corn silk on the condition of human skin, etc. The effects of the combination of crowberry and corn silk were confirmed using the same procedure as described for evaluating the effects of crowberry and hibiscus on the condition of human skin, etc. Four types of test samples were prepared and conducted in groups A to D. The number of panelists was as follows: Group A: 15 people (excipient intake group, ingested by taking two 315 mg tablets), Group B: 15 people (crowberry 170 mg (dry weight) / day, ingested by taking two 315 mg tablets), Group C: 15 people (corn silk 200 mg (dry weight) / day, ingested by taking two 315 mg tablets), and Group D: 15 people (crowberry 85 mg (dry weight) + corn silk 100 mg (dry weight) / day, ingested by taking two 315 mg tablets). The crowberry and corn silk content in the tablets taken in groups B, C, and D was the same among the tablets taken in each group. The panelists are healthy Japanese women aged 35-50, excluding those who meet one or more of the conditions listed in Table 8 above.

[0103] Each panelist took two tablets of the test sample (tablets) orally with water or lukewarm water before bedtime for 14 days. The tablets contained crowberry fruit juice as described in Table 1, and corn silk as dried corn silk powder extract as described in Table 1.

[0104] Survey evaluation (Test method) A questionnaire survey was conducted regarding the condition of human skin, etc., before the start of the continuous use test and 3, 7, and 14 days after the start of the continuous use test.

[0105] Figure 9 shows the results for "skin texture," "wrinkles around the mouth," "prominence of nasolabial folds," "cheek sagging," "under-eye sagging," "face line sagging," "ease of pillow marks," and "perceived skin beauty." In Figure 9, the control group shows the evaluation results for Group A, the black crowberry group shows the evaluation results for Group B, the corn silk group shows the evaluation results for Group C, and the black crowberry + corn silk group shows the evaluation results for Group D.

[0106] The results in Figure 9 show that, in particular, 14 days after the start of the continuous use test, Group D showed improvement in all evaluation items compared to Groups A, B, and C.

[0107] Furthermore, statistical analysis was performed on these results. The statistical analysis was carried out using the Tukey-Kramer method as a multiple comparison test, determining whether or not there was a significant improvement compared to the group being compared. * was used when p < 0.05 and ** when p < 0.01. The results are shown in Table 10. In Table 10, the control group is Group A, crowberry is Group B, corn silk is Group C, and crowberry + corn silk is Group D.

[0108] [Table 10]

[0109] Evaluation of the effects of chrysanthemums and cassia seeds on the condition of human skin, etc. The effects of the combination of chrysanthemum and cassia seed were confirmed using the same procedure as described for evaluating the effects of crowberry and hibiscus on the condition of human skin, etc. Four types of test samples were prepared and conducted in groups A to D. The number of panelists was as follows: Group A: 15 people (excipient intake group, ingested by taking two 315 mg tablets), Group B: 15 people (chrysanthemum 50 mg (dry weight) / day, ingested by taking two 315 mg tablets), Group C: 15 people (cassia seed 100 mg (dry weight) / day, ingested by taking two 315 mg tablets), and Group D: 15 people (chrysanthemum 25 mg (dry weight) + cassia seed 50 mg (dry weight) / day, ingested by taking two 315 mg tablets). The amount of chrysanthemum and cassia seed contained in the tablets taken in groups B, C, and D was the same among the tablets taken in each group. The panelists are healthy Japanese women aged 35-50, excluding those who meet one or more of the conditions listed in Table 8 above.

[0110] Each panelist took two tablets of the test sample (tablets) orally with water or lukewarm water before bedtime for 14 days. The tablets contained dried purple chrysanthemum powder as described in Table 1, and Cassia seed extract as described in Table 1.

[0111] Survey evaluation (Test method) A questionnaire survey was conducted regarding the condition of human skin, etc., before the start of the continuous use test and 3, 7, and 14 days after the start of the continuous use test.

[0112] Figure 10 shows the results for "skin moisture," "skin radiance," "skin texture," "skin wrinkles," and "neck wrinkles," while Figure 11 shows the results for "skin firmness," "cheek sagging," "face line sagging," "susceptibility to pillow marks," "skin water repellency," "aged appearance," and "facial impression / skin beauty." In Figures 10 and 11, the control group shows the evaluation results for Group A, the purple chrysanthemum group shows the evaluation results for Group B, the cassia seed group shows the evaluation results for Group C, and the purple chrysanthemum + cassia seed group shows the evaluation results for Group D.

[0113] The results shown in Figures 10 and 11 demonstrate that, in particular, 14 days after the start of the continuous use test, Group D showed improvement in all evaluation items compared to Groups A, B, and C.

[0114] Furthermore, statistical analysis was performed on these results. The statistical analysis was carried out using the Tukey-Kramer method as a multiple comparison test, determining whether or not there was a significant improvement compared to the group being compared. A value of + was used when p<0.10, * when p<0.05, and ** when p<0.01. The results are shown in Table 11. In Table 11, Group A represents the control, Group B represents purple chrysanthemum, Group C represents cassia seed, and Group D represents purple chrysanthemum + cassia seed.

[0115] [Table 11]

Claims

1. A composition comprising crowberry for promoting collagen production, for use in combination with hibiscus or corn silk.

2. A composition for promoting collagen production, comprising hibiscus or corn silk, for use in combination with crowberry.

3. A composition for promoting collagen production, comprising crowberry and hibiscus or corn silk.

4. A composition comprising crowberry for promoting the production of PDGF-bb, for use in combination with hibiscus or corn silk.

5. A composition comprising hibiscus or corn silk for promoting the production of PDGF-bb, for use in combination with crowberry.

6. A composition comprising crowberry and hibiscus or corn silk for promoting the production of PDGF-bb.

7. A composition according to any one of claims 1 to 6 for improving skin firmness.

8. A composition according to any one of claims 1 to 6, for use such that CA / CB is 0.1 to 10, where CA is the dry weight of crowberry and CB is the dry weight of hibiscus.

9. A composition according to any one of claims 1 to 6, for use such that CA / CD is 0.1 to 10, where CA is the dry weight of crowberry and CD is the dry weight of corn silk.

10. A composition for oral use, according to any one of claims 1 to 6.

11. A composition comprising chrysanthemum to promote collagen production, for use in combination with Cassia seed or Polygonatum odoratum.

12. A composition for promoting collagen production, comprising Cassia seed or Polygonatum odoratum, for use in combination with chrysanthemum.

13. A composition comprising chrysanthemum and Cassia obtusifolia or Polygonatum odoratum for promoting collagen production.

14. A composition according to any one of claims 11 to 13 for improving skin firmness.

15. The composition according to any one of claims 11 to 13, for use such that the ratio of ca / cb is 0.1 to 10, where ca is the dry weight of chrysanthemum and cb is the dry weight of cassia seed.

16. The composition according to any one of claims 11 to 13, for use such that ca / cd is 0.1 to 10, where ca is the dry weight of chrysanthemum and cd is the dry weight of Polygonatum odoratum.

17. A composition for oral use, according to any one of claims 11 to 13.

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