Cosmetic surgery Collagen has been widely used in cosmetic surgery, as a healing aid for burn patients for reconstruction of bone and a wide variety of dental, orthopedic, and surgical purposes. Both human and bovine collagen is widely used as dermal fillers for treatment of wrinkles and skin aging.
接著來看, Reconstructive surgical uses(整形外科手術中的應用) Collagens are widely employed in the construction of the artificial skinsubstitutes used in the management of severe burns.(還是說是用於緊急燒傷情況下人造皮膚) 接下來說說口服: Collagen is also sold commercially in pill form as a supplement to aid joint mobility. However, because proteins are broken down into amino acids before absorption, there is no reason for orally ingested collagen to affect connective tissue in the body, except through the effect of individual amino acid supplementation.(重點來了,維基百科還特定說明了商業中口服膠原是不可取的,在吸收之前會被水解為氨基酸,因此口服吸收膠原和皮膚組織之間沒有什麼關係,除非是通過獨立的氨基酸!) 以上信息來源於維基百科Collagen詞條。
Composition for acceleration of type I collagen production
Abstract
It is an object of the present invention to provide a composition for promoting the production of type I collagen by human skin fibroblasts, and the present invention relates to a composition for promoting type I collagen production containing silybin and a peptide that promotes collagen production (peptide having an amino acid sequence of Gly-Pro-Hyp, Gly-His-Lys, Lys-Thr-Thr-Lys-Ser (SEQ ID NO: 1) or Gly-Glu-Pro-Arg (SEQ ID NO: 2).
Description
This application is the U.S. National Phase under 35 U.S.C. .sctn.371 of International Application PCT/JP2006/314393, filed Jul. 20, 2006, which claims priority to Japanese Patent Application No. 2005-283271, filed Sep. 29, 2005. The International Application was published under PCT Article 21(2) in a language other than English.
TECHNICAL FIELD
The present invention relates to a composition having the effect of promoting the production of type I collagen by human skin fibroblasts.
PRIOR ART
Collagen accounts for approx. one-third of all protein produced in the body. It is found in large quantities in the blood vessel, skin and bone and plays an important function in the formation and building of blood vessel/skin/bone tissues as a cell scaffold. Collagen was long considered a type of protein offering low nutritional value because it is hardly broken down by digestive enzymes. However, people are having a second look at the effectiveness of collagen nowadays after the publication of reports suggesting that ingesting collagen promotes metabolism (Patent Literature 1) or hair growth (Non-patent Literature 1) and that collagen can be utilized as an arthropathy treatment drug (Patent Literature 2). Since collagen decreases with age, it is also considered that a reduction in collagen is a cause of weakening of blood vessels, loss of elasticity and flexibility of skin, and formation of lines and sagging.
Gelatin, which is a thermally denatured form of collagen, is utilized as an additive to improve the texture of food or in the production of cosmetics because of its high viscosity, coagulation property and moisture-keeping property (Patent Literature 3). However, unprocessed collagen and gelatin have high viscosity and are easy to coagulate, and thus in many cases collagen and gelatin are partially hydrolyzed before use. Being a protein, collagen also has antigenicity and therefore ingesting collagen presents a problem in people with allergy. For this reason, converting collagen into a low-molecular-weight form having no antigenicity by means of collagenase for use as a source of protein or fluid infusion component for allergic patients is reported (Patent Literature 4). As for the bioactivities of collagen decomposition products obtained through collagenase, such collagen decomposition products are known to have fibrin coagulation inhibition activity (Patent Literature 5) and anesthetic action (Non-patent Literature 2). There is also a report that collagen decomposition products obtained through Clostridium histolyticum-derived collagenase have 36% of their tripeptide content constituted by Gly-Pro-Hyp, which is the highest Gly-Pro-Hyp ratio found in all substances (Non-patent Literature 3).
An attempt has been made to use a collagen decomposition product containing Gly-Pro-Hyp, obtained through collagenase, as an effective ingredient in external drugs for skin and other products designed to prevent skin aging (Patent Literature 6).
Also, a biocollagen promoter has been developed that contains a collagen decomposition product containing Gly-Pro-Hyp, obtained through collagenase, especially such collagen decomposition product with a molecular weight of 400 or less (Patent Literature 7). A collagen decomposition product obtained through collagenase is assumed to promote collagen synthesis by acting as a material for biocollagen. In addition, peptides that promote collagen production have been developed, including Lys-Thr-Thr-Lys-Ser (SEQ ID NO: 1) being a pentapeptide derived from an .alpha.1 collagen decomposition product (Non-patent Literature 4), Gly-His-Lys being a tripeptide derived from an .alpha.2 collagen decomposition product (Non-patent Literature 5), and Gly-Glu-Pro-Arg (SEQ ID NO: 2) being a pentapeptide derived from an immunoglobulin G decomposition product (Non-patent Literature 6).
On the other hand, compositions have been discovered that promote the production of collagen not by acting as a material for biocollagen. For example, retinoic acid and its derivative retinol (Non-patent Literature 7), as well as silymarin which is a component derived from milk thistle extract (Patent Literature 8), have been developed. In addition, retinoic acid and its derivative retinol (Non-patent Literature 8) and silymarin derived from milk thistle extract (Patent Literature 9) have been shown to also suppress collagenase, which is a collagen decomposition enzyme.
Retinoic acid and its derivative retinol are not suitable for use in practical applications because they cause skin irritation and present other safety issues (Non-patent Literature 9) and are also unstable.
As explained above, various components and compositions have been developed that increase biocollagen. However, none of them have been proven to ensure safety and also demonstrate sufficient effects.
The present invention was developed based on the discovery that a combined use of silybin and various peptides would promote the production of type I collagen synergistically compared to when they are used alone. Patent Literature 1: Japanese Patent Laid-open No. Hei 7-278012 Patent Literature 2: Japanese Patent Laid-open No. Sho 63-39821 Patent Literature 3: Japanese Patent Laid-open No. Sho 52-111600 Patent Literature 4: Japanese Patent Laid-open No. Hei 7-82299 Patent Literature 5: Japanese Patent Laid-open No. Hei 6-46875 Patent Literature 6: Japanese Patent No. 3504205 Patent Literature 7: Japanese Patent Laid-open No. 2001-1310844 Patent Literature 8: WO2004/085429 Patent Literature 9: Japanese Patent Laid-open No. 2002-173424 Patent Literature 10: Japanese Patent Laid-open No. Hei 5-286864 Patent Literature 11: Japanese Patent No. 2948818 Patent Literature 12: Japanese Patent Laid-open No. 2000-169328 Patent Literature 13: Japanese Patent Laid-open No. 2000-169332 Patent Literature 14: Japanese Patent Application No. 2002-255448 Patent Literature 15: Examined Japanese Patent Laid-open No. Hei 5-9406 Patent Literature 16: Examined Japanese Patent Laid-open No. Sho 63-41396 Patent Literature 17: Japanese Patent Laid-open No. 2002-255847 Non-patent Literature 1: Nutrition Reports International, 13, 579, 1976 Non-patent Literature 2: Br. J. Pharmacol., 69, 551, 1980 Non-patent Literature 3: J. Biochem., 50, 486, 1961 Non-patent Literature 4: J. Biol. Chem., 268 (14), 9941-9944, 1993 Non-patent Literature 5: Ann. NY Acad. Sci., 580, p 573 Non-patent Literature 6: Int J Pept Protein Res., 17 (4), p 430-435., 1981 Non-patent Literature 7: J. Invest. Dermatol., Vol. 94, No. 5, p 717-723, 1990 Non-patent Literature 8: Varani J., et al., J. Invest. Dermatol., 116, 480-486, 2000 Non-patent Literature 9: Zouboulis, C. C., Retinoids: is there a New Approach?, IFSCC Magazine, Vol. 3, No. 3, 2000 Non-patent Literature 10: Wagner, H., et al., Arznein. Forsch, 24, 466, 1974. Non-patent Literature 11: Tittel, G., et al., J. Chromatogr., 135, 499, 1977. Non-patent Literature 12: Tittel, G., et al., J. Chromatogr., 153, 227, 1978. Non-patent Literature 13: Quercia, V., et al., J. Chromatography in Biochemistry, Medicine and Environmental Research, Frigerio A. (Ed)., ElsevierScientific Publishing Company, Amsterdam, 1983, p 1. Non-patent Literature 14: Lowry, O et. al., J. Biol. Chem., 193, 265, 1951 Non-patent Literature 15: M. J. Barttek, et al., J. Invest. Dermatol., 58, 114, 1972
SUMMARY OF THE INVENTION
Problems to be Solved by the Invention
It is an object of the present invention to provide a composition for promoting the production of type I collagen by human skin fibroblasts.
Means for Solving the Problems
The inventors examined ways to enhance the production of type I collagen more effectively.
As a result, it was found that a combined use of a collagen-derived peptide that promotes collagen production by acting as a material for collagen, and silybin, would promote the production of type I collagen synergistically, the discovery of which led to the development of the present invention.
In other words, the present invention relates to the following: (1) a composition for promoting type I collagen production, containing silybin and a peptide that promotes collagen production; (2) a composition according to an embodiment, wherein the peptide that promotes collagen production comprises one or two or more types selected from peptides having an amino acid sequence of Gly-Pro-Hyp, Gly-His-Lys, Lys-Thr-Thr-Lys-Ser (SEQ ID NO: 1) or Gly-Glu-Pro-Arg (SEQ ID NO: 2); (3) a composition according to any one of Claims 1 to 4, used for the purpose of preventing and/or improving lines, sagging, dull complexion and pigmentation of skin; (4) a cosmetic containing silybin and one or two or more types selected from peptides having an amino acid sequence of Gly-Pro-Hyp, Gly-His-Lys, Lys-Thr-Thr-Lys-Ser (SEQ ID NO: 1) or Gly-Glu-Pro-Arg; (SEQ ID NO: 2) (5) a food containing silybin and one or two or more types selected from peptides having an amino acid sequence of Gly-Pro-Hyp, Gly-His-Lys, Lys-Thr-Thr-Lys-Ser (SEQ ID NO: 1) or Gly-Glu-Pro-Arg (SEQ ID NO: 2); and (6) a composition according to an embodiment for animals.
EFFECTS OF THE INVENTION
A composition having an excellent effect in promoting type I collagen production by human skin fibroblasts was provided by using silybin in combination with a peptide that promotes collagen production.
Application of a composition conforming to the present invention as a cosmetic, or ingestion of such composition as a food, is expected to improve the resilience and elasticity of skin and thereby prevent and/or improve lines and sagging of skin.
Compositions conforming to the present invention are also safe to skin.