This application is a 371 of PCT/KR01/01059 filed Jun. 21, 2001.
The present invention relates to 3,9-diferulylcoumestrol and a skin cosmetic product containing the same, more particularly to a novel skin cosmetic product capable of improving anti-aging, whitening and hair-seedling effect and remedying skin disorder from a cosmetic point of view.
Skin aging means a condition that wrinkles or droops are formed with age. The latest study about skin aging is largely divided into two ways; a histological approach studying for example the mechanism of matrix formation or destruction of connective tissue such as skin collagen and a immunological approach studying for example the relation between oxidizing stress and aging.
At first, the cause of skin wrinkle and droop in a histological viewpoint, is degeneration of collagenous fiber or ellastin fiber[M. Oshima et al., Matrix, 13, 187(1993); S. Harumiya et al., J. Biocham., 120, 745(1996)]. Further, the lowered supporting force of hypodermic tissue and muscle tissue increases wrinkle. In particular, collagen, which is the original material or collageneous fiber and ellastin, is synthesized in fibroblast and forms collagenous fiber and ellastin.
Cell membrane of fibroblast has signal receptor glycoprotein capable of specifically recognizing nutrition passage and extracellular materials. The receptor is connected to ion transport passage and if the exterior materials approaches the receptor of the fibroblast cell membrane, the signal is transported into the cell, finally to the inside of the nucleus. It is ordered to synthesize collagenous protein and more proteins than ordinary state are synthesized and released out of the nucleus. The protein grows by passing through the various organs of the cell and released from the cell. The released protein becomes a base of collagenous fiber or ellastin among cells and then elastic skin with a strong supporting power. [A. Hayasho et al., Fragnance J., 2, 32(1992)]. However, collagen biosysthesis in corium sharply decreases with age and various stress such as ultraviolet rays or environment pollution, resulting in forming wrinkle.[M.Oshima et al., Matrix, 13, 187(1993)].
In immunological viewpoint, oxidative stress in or out of human body destroys cells and biological connective tissue, which increases the number of wrinkles and makes them deeper. Furthermore, as the bio-synthetic ability of the biological anti-oxidant materials becomes lowered with age, the activation of oxidizing materials such as active oxygen which is introduced out of the body or metabolically inevitably generated cannot be prevented, resulting in accelerating wrinkle formation.[L. H. Kligman et al., J. Invest. Dermatol. 93, 210 (1989); H. Tanaka et al., Arch. Dermatol. Res., 285, 352(1993); M. D. Carbonare et al., J. Photochem. Photobiol. B. Biol., 14, 105(1992); T. Okada et al., Fragnance J., 11,23 (1993)]. Therefore, to prevent oxidization of body including skin, artificial intake or application of anti-oxidant agent is essential.
There are a number of materials with anti-oxidant function in nature. The principle of anti-oxidant function could be explained in the following way. Lipids forming cell membranes are easily attacked by peroxides or other active oxygen species generated from environmental factor such as ultraviolet rays or pollution or internal factor such mental stress. They are changed into peroxide lipid and forms radical polymer, resulting in destruction of cell membrane [T. Shibamoto et al., American Chem Soc 154(1994)]. The destruction of cell membrane protecting intracellular materials causes cell necrosis and skin aging. Anti-oxidant materials is oxidized instead before the cell membrane lipid is oxidized, and prevent lipids from being oxidized. So far, anti-oxidant materials used in cosmetics are various plant extract such as tocopherol and ascorbic aid. However, there is a problem that they are very unstable or do not show enough effect.
In present, for the most part of the functional materials applied to anti-aging cosmetics, the anti-aging effect have been discussed only in the basis of in vitro test results and clinic test results, instead of proving histological improvement, because of technical limitation. That is, the anti-aging materials being developed as cosmetics these days are focused only to the in vitro immunological effect. Therefore, it is not believed that such materials bring a substantial anti-wrinkle effect.
Under the above circumstance, the inventors invented 3,9-diferurylcoumestrol synthesized from ferulic acid and coumestrol with superior anti-oxidant force, which can solve chemical unstability or lack of effect and has histological and immunological effect for restraining aging and wrinkle formation.
It is not easy to develop materials with a substantial anti-aging function. As described above, the sources and products marketed as an anti-aging concept were concentrated on anti-aging effect, but could not obtain desired effects in practice.
The anti-oxidant effect can protect against the attack of internally generated or externally introduced active oxygen species to some extent However, such function has not guaranteed the substantial anti-aging effect in a histological standpoint, such as visible elimination of wrinkles. Therefore, it has been required to develop materials or products which have immunological anti-aging function by anti-oxidant function and further can accelerate skin collagen generation, so that skin recovering and skin elasticity and wrinkle improvement performance are all excellent
The inventors tried to develop material which can intensifies immunological function as a basic direction for anti-aging and histologically improve skin wrinkles. Considering the above, we came to synthesize a new concept of anti-aging material from ferulic acid known as its excellent anti-oxidant ability and coumestrol known as its excellent effect for accelerating collagen synthesis, as precursors.
Ferulic acid exists in asafetida, pine resin, leaf of rice plant, and is known as its antibiotic and anti-cancer ability and mild anti-oxidant property.[M. G. Smart et al., Aust J. Plant Physical. 6, 485(1979)]. Further, it is known as having a thrombus coagulation preventing function and used as an antiseptic of food.[T. Tsukiya et al., Jpn. Lolai 7518621(1975), C. A.83, 7602v(1975)]. Ferulic acid was extracted from a plant resin and named by H. Hiasiwetz and his colleagues of Australia in 1866 [H. Hiasiwetz et al., Ann. 138, 61(1866)].
The active oxygen species derived from oxygen molecule are essentially generated in the metabolism and their concentration should be maintained in the human body. Too low concentration has a bad effect on the metabolism and too high concentration causes peroxidization of bio-molecules such as cell lipid membranes of the organs[A. M. Kligman et al., J. Am. Acad. Dermatol., 15,836(1986); E. J. Van Scott et al., Cutis., 43, 222(1989)].
Ferulic acid has an mild oxidizing force over various active oxygen species derived from oxygen molecule and an strong oxidizing force over oxidative transitional metals such as Iron ion or Copper ion.[M. G. Smart et al., Aust J. Plant Physiol. 6, 485(1979)]. It is further reported that the Ferulic acid is used for preventing auto-oxidization of natural oil such as linseed oil. Ferulic acid has been proved that it is an active material as an ant-oxidant material in the filed of cosmetic, medicine and food.
However, Ferulic acid has only simple anti-oxidant function and is mainly used as an additive for preventing oxidization of effective components of products by transitional metal or other introduced active oxygen species[T. Tsukiya et al., Jpn. Kokai 751862191975], C. A. 83, 7602v(1975)].
Coumestrol is generally found in leguminous plants and has mild anti-oxidant effect and is known to have anti-inflammation, anti-fungal and anti-virus action [Darbarwar, M., et al., J. Sci. Ind. Res., 35, 297(1982); Jeffrey, B. H. et al., Phytochemical Dictionary, Taylor and Francis, London, pp 418(1933)].
Although its accurate mechanism is not revealed, it is known to accelerate production of connective tissue such as collagen in skin and internal organs and believed to have an anti-aging or anti-wrinkle effect [Bickoff, E. M., et al., J. Anim. Sci., 19,4(1960)]. However, the amount of coumestrol contained in a black soybean is extremely small and thus simple extract method does not lead to desired effect Therefore, the objective of the invention is to develop a new material with substantial anti-aging effect and skin-elasticity improving effect together with whitening effect in cosmetics by producing coumestrol in a mass-synthetic way and connecting it with a material with an excellent anti-oxidant effect such as ferulic acid.
Although about three synthetic method of coumestrol has been known. It is not generalized to synthesize coumestrol. The inventors used one of the three methods [E. M. Bickoff, et al., J. Am. Chem. Soc., 80, 4381(1958)]. The used method is total synthesis consisting of total 7 stages. The present invention produces a material having strong anti-oxidant effect together with anti-aging and whitening effect of skin by accelerating the regeneration of skin connective tissue.