WO2008147022A1 - Anti-wrinkle composition for external applications to the skin containing biflavonoid derivatives - Google Patents
Anti-wrinkle composition for external applications to the skin containing biflavonoid derivatives Download PDFInfo
- Publication number
- WO2008147022A1 WO2008147022A1 PCT/KR2008/001038 KR2008001038W WO2008147022A1 WO 2008147022 A1 WO2008147022 A1 WO 2008147022A1 KR 2008001038 W KR2008001038 W KR 2008001038W WO 2008147022 A1 WO2008147022 A1 WO 2008147022A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cosmetic composition
- biflavonoid
- derivatives
- improving skin
- skin wrinkles
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9739—Bryophyta [mosses]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9741—Pteridophyta [ferns]
- A61K8/9749—Filicopsida or Pteridopsida
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9771—Ginkgophyta, e.g. Ginkgoaceae [Ginkgo family]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9794—Liliopsida [monocotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
Definitions
- the present invention relates to a cosmetic composition containing biflavonoid derivatives as an active ingredient for improving skin wrinkles caused by aging.
- the present invention relates to an anti-wrinkle cosmetic composition containing biflavonoid derivatives as an active ingredient, which is safe for the application on the skin without side-effects, induces procollagen production, inhibits MMP-I, and has the effect of improving wrinkles generated by UV.
- Skin aging is largely divided into two groups according to the reason; one is intrinsic aging caused by the aging of the structureand physiological functions of the skin and the other is extrinsic aging caused by accumulated stress given from outside such as sunrays, etc.
- UV among the sunrays is well-known as a reason of aging.
- the horny layer of the skin becomes thicker and the major structural constituents of the skin, collagen and elastin, are denatured, resulting in wrinkles by lack of elasticity.
- Skin aging accompanies various functional, structural changes.
- the skin composing components, epidermis, dermis and subcutaneous tissue become thinner.
- ECM extracellular matrix
- ECM is composed of two main components. One is elastic fiber taking 2-4% of ECM and the other is collagen taking 70-80% of ECM. According to aging, the skin greatly loses its elasticity, which is resulted from the decrease of collagen and elastin.
- the collagen and elastin are regulated by various factors.
- collagen and elastin are decomposed by the expression of matrix metallo protease such as collagenase and elastase, so that the collagen content in skin is reduced.
- matrix metallo protease such as collagenase and elastase
- retinol and retinoic acid The most effective method to prevent skin aging so far is to use retinol and retinoic acid.
- the improvement effect of retinol and retinoic acid on wrinkles and elasticity has been well-informed through previous reports (Dermatology therapy, 1998, 16, 357 ⁇ 364) .
- the retinoid has positive effects such as wrinkle or elasticity improvement, it has problems of irritating skin even with only a small amount and being so unstable that it is easily oxidized and denatured when being exposed on the air, -and it causes the limitation to use. Therefore, studies have been going on to make the retinoid more stable, but skin irriation, the stability problems, remains unsolved.
- the present inventors studied to find out a novel anti- aging material that is safe in human skin and has excellent anti-wrinkle effect among natural plant materials.
- the natural plant originated biflavonoid derivatives not only inhibited the activity of collagenase but also exhibited improvement effect on wrinkles caused by UV and at the same time excellent safety on human skin.
- the present inventors further observed that the biflavonoid derivatives had excellent preventive and therapeutic effect on skin aging. So, the present inventors completed this invention by confirming that a cosmetic composition for improving skin wrinkles of the invention which contained biflavonoid derivatives by 0.001-10 weight% more preferably 0.01-5 weight! for the total weight of the composition had excellent wrinkle improvement effect.
- the present invention is completed by the following steps: preparing an extract containing biflavonoid derivatives from natural plants by using water or an organic solvent; separating the biflavonoid derivatives by separation/purification process; measuring procollagen productivity and inhibition of collagenase decomposition; and confirming suppressing effect of the biflavonoid derivatives on wrinkles caused by UV.
- the biflavonoid derivatives can be extracted from medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica, Lonicera japonica, etc, but not always limited thereto.
- the biflavonoid derivatives can be included by 0.001-10 weight% for the total weight of the cosmetic composition for prevention and improvement of wrinkles and more preferably included by 0.01-5 weight%.
- biflavonoid which is the active ingredient of the composition for prevention and improvement of wrinkles is described in detail.
- the b ' iflavonoid derivatives, the active ingredient of the cosmetic composition for improving wrinkles, are the compounds represented by the following formulas 1 - 7.
- the biflavonoid derivatives represented by formulas 1 - 7 can be obtained from natural medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica, by the conventional extraction and separation method.
- To extract a target material stems, roots and leaves were dehydrated properly, followed by macerated or dehydrated only.
- the target material was purified by the conventional purification method known to those in the art.
- the synthetic compound or its derivatives corresponding to the above plant originated biflavonoid derivatives represented by formulas 1 - 7 .can be purchased on the market or can be synthesized by the conventional method well-known to those in the art. Specifically, the compound can be extracted from medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica, or synthesized by the conventional chemical synthesis.
- panduratin derivatives represented by formulas 1 - 7 can be separated and purified from the extract extracted from Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica by using an organic solvent or from oil obtained from the above by compressing.
- Biflavonoid derivatives can be extracted from such plants as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica, but not always limited thereto.
- Biflavonoid is a compound that is naturally generated in vascular plants and has the morphology of dimer formed by C-C or C-O-C bond. It is believed that the reason why the biflavonoid is in dimer form in plants is that when a stimulus is coming in from outside, a plant activates its in vivo protection system to protect itself, in which single molecular polyphenol structure is developed into biflavonoid.
- the structure of biflavonoid is divided largely into two groups according to the bond types; one is amentoflavone having C-C bond and the other is ochnaflavone having C-O-C bond.
- the biflavonoid derivatives of the present invention can be separated and purified from the organic solvent extract or oil prepared from medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica.
- the extraction solvent can be water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane, cyclohexane, petroleum ether or a mixture thereof.
- the separation and purification of biflavonoid derivatives from the natural plant extract can be performed by column chromatography filled with synthetic resins such as silica gel or active alumina and High performance liquid chromatography (HPLC) respectively or together.
- synthetic resins such as silica gel or active alumina and High performance liquid chromatography (HPLC) respectively or together.
- HPLC High performance liquid chromatography
- the methods for extraction, separation and purification of the active ingredient are not always limited thereto.
- the preferable content of the biflavonoid derivatives of the present invention in a cosmetic composition for improving wrinkles is 0.001-10 weight% for the total weight of the composition. If the content is less than 0.001 weight%, anti- wrinkle effect will not be obtained. In the meantime, if the content is more than 10 weight%, safety or formulation will matter.
- the biflavonoid derivatives are preferably contained by 0.01-5 weight% for the total weight of the composition.
- the content of the biflavonoid derivatives is not always limited thereto.
- the cosmetic composition for improving wrinkles of the present invention can additionally include other anti-wrinkle elements that can raise the anti-wrinkle effect of the composition as long as they do not damage the original targeted anti-wrinkle effect.
- the formulation forms of the cosmetic composition for improving wrinkles of the present invention are not limited, and can be nutritional toner, softener, nutritional cream, massage cream, pack, gel, astringent, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, powder, body lotion, body oil and body essence, etc.
- the biflavonoid derivatives can be isolated from natural plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica, but herein Selaginella tamariscina was selected as an example.
- Dried Selaginella tamariscina was pulverized and mixed with alcohol, followed by elution. Then, the solvent was eliminated and the crude extract was concentrated. The concentrated crude extract was mixed with ethyl acetate, and then ethyl acetate soluble component was extracted. Preferably, this extraction process was repeated at least three times. The extracted ethyl acetate soluble component contains biflavonoid derivatives, which already exhibited collagenase inhibitory activity despite it was not a single component. Then, ethyl acetate was eliminated to concentrate ethyl acetate soluble component. According to the difference of polarity, each component was separated.
- a solvent was prepared by mixing chloroform, methanol and water at the ratio of 10 : 1 : 0.5 (v/v) .
- the component was mixed with this solvent and 10 fractions were separated thereby.
- the fractions proceeded to column chromatography to separate pure single anti-wrinkle component.
- the anti-wrinkle component obtained from the above extraction and separation was proved to be amentoflavone having the structure of formula 1.
- the methods for extracting biflavonoid derivatives, amentoflavone, 2' , 8"-biapigenin, taiwaniflavone, robustaflavone, ginkgetin and ochnaflavone, from Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica are similar to the above method.
- Fig. 1 is a set of photographs illustrating the improvement of wrinkles caused by ultraviolet (UV) by biflavonoid derivatives.
- Example 1 Extraction of sumaflavone 1.8 kg of dried Selaginella tamariscina was cut into small pieces, followed by extraction with methanol at 80 ° C for 4 hours, which was repeated three times. The obtained methanol extract was concentrated under the reduced pressure. 78.7 g of the concentrate was dissolved in water, to which methylene chloride was added as an extraction solvent, followed by extraction over three times. The methylene chloride soluble fraction (21.7g) was obtained and the remnants proceeded to extraction again using ethyl acetate or butanol as an extraction solvent over three times.
- the ethyl acetate soluble fraction ( ⁇ .8g), the butanol soluble fraction (7.8g) and the remaining water fraction (16.2 g) were obtained.
- ⁇ .8g of the ethyl acetate soluble fraction proceeded to silica gel column chromatography.
- a mixed solvent comprising chloroform, methanol and water at the ratio of 10:1:0.1 (v/v) was used as a column elution buffer.
- Column chromatography was performed with raising methanol content slowly to increase polarity of the mixed solvent, resulting in 6 fractions (El- E6) .
- Amentoflavone, 2' , 8"-biapigenin, taiwaniflavone, robustaflavone, ginkgetin and ochnaflavone were also prepared by the same manner as described above.
- Fibroblasts separated from human skin were inoculated in a 24-well plate by 10 6 cells/well, followed by culture until they grew 90%. Then, the cells were cultured in a serum-free medium for 24 hours. 4-substituted benzoic acid derivative compound having 3, 4-methylenedioxy or 3, 4-ethylenedioxybenzene moiety, obtained in Examples 1-2, was dissolved in the serum- free medium was treated thereto at the concentration of 10 ⁇ 4 , followed by culture in a CO 2 incubator for 24 hours. Supernatant was separated and procollagen level was measured using procollagen type 1 ELISA kit. The results are shown in Table 1 and the biosynthesis capacity was presented by the ratio to non-treated group (considered as 100%) . [Table 1]
- Human fibroblasts were inoculated in a 96-well microtiter plate containing DMEM (Dulbecco's Modified Eagle's Media) supplemented with 2.5% FBS at the concentration of 5,000 cells/well, followed by culture till the cells grew 70-80%.
- the sample compound was treated thereto at the concentration of 10 "4 for 24 hours and then the cell culture solution was collected.
- Collagenase production in the cell culture solution was measured by using a commercial collagenase measuring kit (Catalog #: RPN 2610, Amersham Pharmacia, USA).
- the collected cell culture solution was loaded in a 96-well plate evenly distributed with the first collagenase antibody, followed by antigen-antibody reaction in a thermostat for 3 hours.
- the chromophore-conjugated second collagen antibody was added to the 96-well plate, followed by reaction for 15 minutes. 15 minutes later, coloring material was added thereto to induce color development for 15 minutes at room temperature and then the reaction was terminated by adding IM sulfuric acid.
- the reaction solution was yellow. According to the degree of the reaction, the degree of yellow color varied, optical density ⁇ s (OD405) of the yellow 96-well plate was measured by using a spectrophotometer and collagenase production was calculated by mathematical formula 1. At this time, the OD of the cell culture solution not- treated with the sample compound was considered as control.
- Collagenase Expression Level (%) (OD of the group treated with the sample compound/0D of control) XlOO
- MMP-I matrix metallo protease
- UV was irradiated to the mice from 70 cm distance three times a week for 10 weeks (total 30 times) to cause wrinkles.
- the sample material and the positive control material were transdermally administered by 100 ⁇ L, twice a day (morning/afternoon) , 5 days a week (Monday - Friday) for
- a cosmetic composition for improving wrinkles containing biflavonoid derivatives can be selected at random from the group consisting of nutritional cream, nutritional lotion, massage cream, nutritional essence, and softener, etc.
- Nutritional toner (milk lotion)
- Nutritional toner containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
- Softener containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
- Nutritional cream containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
- Pack containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
- Gel containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
- the biflavonoid derivatives of the present invention interact with biflavonoid receptor to increase procollagen biosynthesis, so that they can have the effect of inhibiting wrinkle generation caused by lack of skin elasticity resulted from the denaturation of collagen, one of the important skin components, and of inhibiting the expression of collagenase, the enzyme decomposing collagen, and thereby increases improvement of wrinkles caused by UV. Therefore, the cosmetic composition containing the biflavonoid derivatives as an active ingredient of the present invention can be effectively used as a cosmetic composition or an agent for improvement and prevention of wrinkles without side effects .
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Mycology (AREA)
- Dermatology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
The present invention relates to a cosmetic composition for improving skin wrinkles, which contains biflavonoid derivatives as an active ingredient. The cosmetic composition containing the biflavonoid derivatives of the present invention not only is safe for application on the skin without side-effects but also improves wrinkles caused by UV through procollagen production and MMP-I inhibition.
Description
[DESCRIPTION]
[invention Title]
ANTI-WRINKLE COMPOSITION FOR EXTERNAL APPLICATIONS TO THE SKIN CONTAINING BIFLAVONOID DERIVATIVES
[Technical Field]
The present invention relates to a cosmetic composition containing biflavonoid derivatives as an active ingredient for improving skin wrinkles caused by aging.
[Background Art]
The present invention relates to an anti-wrinkle cosmetic composition containing biflavonoid derivatives as an active ingredient, which is safe for the application on the skin without side-effects, induces procollagen production, inhibits MMP-I, and has the effect of improving wrinkles generated by UV.
Every living bodies experience aging as they get old and the skin is not an exception. The effort to postpone aging has been constantly made and questions on 'what is aging' and 'what causes aging' have been continuously asked.
Skin aging is largely divided into two groups according to the reason; one is intrinsic aging caused by the aging of the structureand physiological functions of the skin and the
other is extrinsic aging caused by accumulated stress given from outside such as sunrays, etc. In particular, UV among the sunrays is well-known as a reason of aging. When the skin is exposed on UV for a long time, the horny layer of the skin becomes thicker and the major structural constituents of the skin, collagen and elastin, are denatured, resulting in wrinkles by lack of elasticity.
Skin aging accompanies various functional, structural changes. As for structural changes on skin by aging, the skin composing components, epidermis, dermis and subcutaneous tissue become thinner. In addition, ECM (extracellular matrix) of dermis which is responsible for elasticity and tension of skin is denatured. ECM is composed of two main components. One is elastic fiber taking 2-4% of ECM and the other is collagen taking 70-80% of ECM. According to aging, the skin greatly loses its elasticity, which is resulted from the decrease of collagen and elastin. The collagen and elastin are regulated by various factors. For example, collagen and elastin are decomposed by the expression of matrix metallo protease such as collagenase and elastase, so that the collagen content in skin is reduced. Once collagen and elastin are reduced in dermis, skin becomes rough and loses elasticity, one of the symptoms of aging, and gets more wrinkles. So, studies have been undergoing to prevent the decrease of
collagen and elastin, the cause of elasticity loss.
The most effective method to prevent skin aging so far is to use retinol and retinoic acid. The improvement effect of retinol and retinoic acid on wrinkles and elasticity has been well-informed through previous reports (Dermatology therapy, 1998, 16, 357~364) . However, although the retinoid has positive effects such as wrinkle or elasticity improvement, it has problems of irritating skin even with only a small amount and being so unstable that it is easily oxidized and denatured when being exposed on the air, -and it causes the limitation to use. Therefore, studies have been going on to make the retinoid more stable, but skin irriation, the stability problems, remains unsolved. As an alternative, a method inhibiting the activity of enzymes hydrolyzing collagen and elastin such as collagenase, elastase and matrix metallo protease has been proposed and thus inhibitors capable of inhibiting the activity of such enzymes have been actively studied. Particularly, natural plant materials are safe and have many useful components, so that they can be a good target for the screening of an anti-wrinkle agent. In fact, it has been long tried to find out a natural plant material which is safe in human skin and has anti-wrinkle effect.
It has been disclosed recently that the increase of the activities of collagenase decomposing collagen and matrix
metallo protease is one of the reasons of wrinkle generation. Therefore, these enzymes are drawing our attention as targets for anti-wrinkle activity.
[Disclosure]
[Technical Problem]
The present inventors studied to find out a novel anti- aging material that is safe in human skin and has excellent anti-wrinkle effect among natural plant materials. As a result, the present inventors found out that the natural plant originated biflavonoid derivatives not only inhibited the activity of collagenase but also exhibited improvement effect on wrinkles caused by UV and at the same time excellent safety on human skin. The present inventors further observed that the biflavonoid derivatives had excellent preventive and therapeutic effect on skin aging. So, the present inventors completed this invention by confirming that a cosmetic composition for improving skin wrinkles of the invention which contained biflavonoid derivatives by 0.001-10 weight% more preferably 0.01-5 weight! for the total weight of the composition had excellent wrinkle improvement effect.
Therefore, it is an object of the present invention to provide a cosmetic composition for improvement and prevention of wrinkles that contains biflavonoid derivatives as an active
ingredient so as to improve wrinkles without side effects.
[Technical Solution)
To achieve the above object, the present invention is completed by the following steps: preparing an extract containing biflavonoid derivatives from natural plants by using water or an organic solvent; separating the biflavonoid derivatives by separation/purification process; measuring procollagen productivity and inhibition of collagenase decomposition; and confirming suppressing effect of the biflavonoid derivatives on wrinkles caused by UV.
In the structure of the biflavonoid derivatives, two flavonoid molecules form a dimer by C-C or C-O-C bond. The biflavonoid derivatives can be extracted from medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica, Lonicera japonica, etc, but not always limited thereto.
The biflavonoid derivatives can be included by 0.001-10 weight% for the total weight of the cosmetic composition for prevention and improvement of wrinkles and more preferably included by 0.01-5 weight%.
Hereinafter, biflavonoid which is the active ingredient of the composition for prevention and improvement of wrinkles is described in detail.
The b'iflavonoid derivatives, the active ingredient of the cosmetic composition for improving wrinkles, are the compounds represented by the following formulas 1 - 7.
<Formula 1>
Sumaflavone
<Formula 2>
2' , 8"-biapigenin
<Formula 3>
Taiwaniflavone
<Formula 4>
Amentoflavone
<Formula 5>
Robustaflavone
<Formula 7>
Ochnaflavone
The biflavonoid derivatives represented by formulas 1 - 7 can be obtained from natural medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica, by the conventional extraction and separation method. To extract a target material, stems, roots and leaves were dehydrated properly, followed by macerated or dehydrated only. The target material was purified by the conventional purification method known to those in the
art.
The synthetic compound or its derivatives corresponding to the above plant originated biflavonoid derivatives represented by formulas 1 - 7 .can be purchased on the market or can be synthesized by the conventional method well-known to those in the art. Specifically, the compound can be extracted from medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica, or synthesized by the conventional chemical synthesis.
As other preferable compounds of the present invention, panduratin derivatives represented by formulas 1 - 7 can be separated and purified from the extract extracted from Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica by using an organic solvent or from oil obtained from the above by compressing.
Biflavonoid derivatives can be extracted from such plants as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica, but not always limited thereto.
Biflavonoid is a compound that is naturally generated in vascular plants and has the morphology of dimer formed by C-C or C-O-C bond. It is believed that the reason why the biflavonoid is in dimer form in plants is that when a stimulus
is coming in from outside, a plant activates its in vivo protection system to protect itself, in which single molecular polyphenol structure is developed into biflavonoid. The structure of biflavonoid is divided largely into two groups according to the bond types; one is amentoflavone having C-C bond and the other is ochnaflavone having C-O-C bond. Biological functions and effects of biflavonoid have also been reported regarding antitumor (J Nat Prod, 1999, 1668-71.)/ antimicrobial (Phytochem, 2005, 1922-26) , antiparasitic, Neuroprotective (Bioorg and Medichem.Lett, 2005, 3588-91), antioxidant (Phytochem, 2005, 2238-47), antifungal (Arch Pharm Res, 2006, 746-751) and Antiinflamination (Pharma Res, 2005, 539-546., Arch Biochem and Biophy, 2006, 136-146) activities. However, there has been no report on anti-wrinkle effect of biflavonoid derivatives, yet.
The biflavonoid derivatives of the present invention can be separated and purified from the organic solvent extract or oil prepared from medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica. The extraction solvent can be water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane, cyclohexane, petroleum ether or a mixture thereof. The separation and purification of
biflavonoid derivatives from the natural plant extract can be performed by column chromatography filled with synthetic resins such as silica gel or active alumina and High performance liquid chromatography (HPLC) respectively or together. However, the methods for extraction, separation and purification of the active ingredient are not always limited thereto.
The preferable content of the biflavonoid derivatives of the present invention in a cosmetic composition for improving wrinkles is 0.001-10 weight% for the total weight of the composition. If the content is less than 0.001 weight%, anti- wrinkle effect will not be obtained. In the meantime, if the content is more than 10 weight%, safety or formulation will matter. To enhance the anti-wrinkle effect and convenience in formulation, the biflavonoid derivatives are preferably contained by 0.01-5 weight% for the total weight of the composition. However, the content of the biflavonoid derivatives is not always limited thereto. The cosmetic composition for improving wrinkles of the present invention can additionally include other anti-wrinkle elements that can raise the anti-wrinkle effect of the composition as long as they do not damage the original targeted anti-wrinkle effect.
The formulation forms of the cosmetic composition for improving wrinkles of the present invention are not limited, and can be nutritional toner, softener, nutritional cream, massage cream, pack, gel, astringent, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, powder, body lotion, body oil and body essence, etc.
Method for extracting biflavonoid derivatives
As an example of methods for extracting the biflavonoid derivatives of the present invention, the extraction method of sumaflavone is described in detail hereinafter.
The biflavonoid derivatives can be isolated from natural plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica, but herein Selaginella tamariscina was selected as an example.
Dried Selaginella tamariscina was pulverized and mixed with alcohol, followed by elution. Then, the solvent was eliminated and the crude extract was concentrated. The concentrated crude extract was mixed with ethyl acetate, and then ethyl acetate soluble component was extracted. Preferably, this extraction process was repeated at least three times. The extracted ethyl acetate soluble component contains biflavonoid derivatives, which already exhibited collagenase inhibitory activity despite it was not a single component.
Then, ethyl acetate was eliminated to concentrate ethyl acetate soluble component. According to the difference of polarity, each component was separated. For example, a solvent was prepared by mixing chloroform, methanol and water at the ratio of 10 : 1 : 0.5 (v/v) . The component was mixed with this solvent and 10 fractions were separated thereby. The fractions proceeded to column chromatography to separate pure single anti-wrinkle component.
The anti-wrinkle component obtained from the above extraction and separation was proved to be amentoflavone having the structure of formula 1.
The methods for extracting biflavonoid derivatives, amentoflavone, 2' , 8"-biapigenin, taiwaniflavone, robustaflavone, ginkgetin and ochnaflavone, from Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana, Nandina domestica and Lonicera japonica are similar to the above method.
[Description of Drawings] The above and other objects, features and advantages of the present invention will become apparent from the following description of preferred embodiments given in conjunction with the accompanying drawings, in which:
Fig. 1 is a set of photographs illustrating the improvement of wrinkles caused by ultraviolet (UV) by biflavonoid derivatives.
[Best Mode]
Practical and presently preferred embodiments of the present invention are illustrative as shown in the following Examples.
However, it will be appreciated that those skilled in the art, on consideration of this disclosure, may make modifications and improvements within the spirit and scope of the present invention.
Example 1: Extraction of sumaflavone 1.8 kg of dried Selaginella tamariscina was cut into small pieces, followed by extraction with methanol at 80°C for 4 hours, which was repeated three times. The obtained methanol extract was concentrated under the reduced pressure. 78.7 g of the concentrate was dissolved in water, to which methylene chloride was added as an extraction solvent, followed by extraction over three times. The methylene chloride soluble fraction (21.7g) was obtained and the remnants proceeded to extraction again using ethyl acetate or butanol as an extraction solvent over three times. As a result, the ethyl
acetate soluble fraction (β.8g), the butanol soluble fraction (7.8g) and the remaining water fraction (16.2 g) were obtained. β.8g of the ethyl acetate soluble fraction proceeded to silica gel column chromatography. A mixed solvent comprising chloroform, methanol and water at the ratio of 10:1:0.1 (v/v) was used as a column elution buffer. Column chromatography was performed with raising methanol content slowly to increase polarity of the mixed solvent, resulting in 6 fractions (El- E6) . Among these 6 fractions, the third fraction (E3) proceeded to silica gel column chromatography (chloroformimethanol : water=8 : 1 : 0.1) , RP-18 column chromatography (methanol : water=2 : 1, Merck, Lichroprep RP-18, 40-63 μm, L610400138), and sephadex LH-20 column chromatography (methanol :water=4 : 1, Lipophilic Sephadex LH 20, 25-100 μm, Sigma, Lot 81klO92) stepwise to give compound 1 (sumaflavone) .
Amentoflavone, 2' , 8"-biapigenin, taiwaniflavone, robustaflavone, ginkgetin and ochnaflavone were also prepared by the same manner as described above.
Example 2 : Determination of the structure of panduratin A compound
To determine the structure of the single material separated in Example 1, 1H-NMR spectrum and 13C-NMR spectrum
were measured at 500 MHz and 125MHz (solvent : DMSO) respectively. The results were as follows.
The results of 1H-NMR and 13C-NMR were compared with the conventional study results to identify the structure and the references are shown below.
Lin, L. -C, Kuo, Y. -C, and Chou, C-J. (2000) Cytotoxic biflavonoids from Selaginella delicatula. J. Nat. Prod., 63, 627-630.
Markham, K. R., Sheppard, C, and Geiger, H. (1987) 13C NMR studies of some naturally occurring amentoflavone and hinokiflavone biflavonoids. Phytochemistry, 26, 3335-3337.
Chen, S. -C, Liu, H. -K., and Kuo, Y. -H. (2004) Two new compounds from the leaves of Calocedrus microlepic var. formosana. Chem. Pharm. Bull., 52, 762-763. Chari, V. M., Ilyas, M., Wagner, H., Neszmelyi, A., Chen, F. -C, Chen,
L. -K., Lin, Y. -C, and Lin, Y. -M. (1977) 13C-NMR spectroscopy of biflavonoids. Phytochemistry, 16, 1273-1278.
The structures of 2' , 8"-biapigenin, taiwaniflavone, robustaflavone, amentoflavone , ginkgetin and ochnaflavone were also determined by the same manner as described above and the results are shown below.
Compound 1 (sumaflavone)
1H-NMR (CD3OD, 500 MHz) δ 6.25 (IH, s, H-3) , 6.12 (2H, s, H-6, H-8), 8.23 (IH, s, H-2 ' ) , 7.08 (IH, d, J=8.5 Hz, H-5'),
7.86 (IH, d, J=8.5 Hz, H-61) , 6.58 (IH, s, H-3") , 7.63(2H, d, J=8.0 Hz, H-21 1 1 , H-6' " ) , 6.60 (2H, d, J=8.0 Hz, H-3I I ?, H- 5' ") .
13C-NMR (CD3OD, 125MHz) 5162.34 (C-2) , 103.53(03) , 183.70(04) , 163.09(05) , 100.94 (06) , 163.09(07) , 95.74 (08) , 159.56(09) , 104.75(C-IO) , 121.75(C-I' ) , 132.90(02') ,
124.76(03') , 166.54 (C-41) , 120.71(05' ) , 127.81(06') ,
162.76(02") , 103.17 (03") , 183.97 (C-4" ) , 163.73(05", C-6", C-7") , 108.65(08") , 156.73(09") , 104.10 (C-IO") , 123.28 (C- I" 1 ) , 129.44 (02' " ) , 116.96(03' ") , 165.58 (04' " ) ,
116.96(05" ' ) , 129.44 (06' " ) .
Compound 2 (2' , 8"-biapigenin)
1H-NMR (CD3OD, 500 MHz) δ 6.51 (IH, S, H-3) , 6.13 (IH, s,
H-6) , 6.39 (IH, s, H-8) ,7.92 (IH, s, H-31) , 7.04 (IH, d, J=7. O Hz, H-51 ) , 7.76 (IH, d, J=7.0 Hz, H-61) , 6.51 (IH, s, H-3") ,
6.32(1H, s, H-6") , 7.44 (2H, d, J=8.0 Hz, H-2" 1, H-6" 1),
6.68 (2H, d, J=8.0 Hz, H-3' " , H-5" ') .
13C-NMR (CD3OD, 125 MHz) δ 166.22 (C-2) , 103.43(03) , 184.81(04) , 163.24 (05) , 100.32(06) , 166.02(07) , 95.30(08) , 159.38 (09) , 105.49* (C-IO) , 121.60(C-I1) , 121.60 (C-2 ' ) ,
132.91(03') , 161.00(04") , 117.42(05') , 129.05(06'),
162.57 (C-2") , 104.07 (03") , 184.23 (C-4" ) , 163.59(05") ,
100.11(06") , 163.59(07") , 105.32(08") , 156.53(09") ,
105.39*(O10") , 123.29(C-I' " ) , 129.41(02" ' ) , 116.94 (03' " ) ,
162.57 (04" ') , 116.94 (C-S1 1 1 ) , 129.41(0-6' " ) . Compound 3 (taiwanif lavone)
1H-NMR (CD3OD, 500 MHz) δ 6.53 (IH, s, H-3) , 6.08 (IH, s,
H-6) , 7.64 (2H, d, J=8.5 Hz, H-2 ' , H-6') , 6.57-6.59 (3H, s, H- 3', H-51, H-3") , 6.53 (IH, s, H-6") , 6.08 (IH, s, H-8") ,
8.26(1H, br d, J=2.0 Hz, H-2'") , 7.08 (IH, d, J=8.5 Hz, H-
5' " ) , 7.86 (IH, br dd, J=8.5, 2.0 Hz, H-6' " ) .
13C-NMR (CD3OD, 125MHz) 5166.05a (C-2) , 109.07 (C-3) , 183.89b(C-4) , 165.63a(C-5) , 102.93(C-6) , 163.71a (C-7) , 96.72(C- 8) , 159.84c(C-9) , 103.84(C-IO) , 122.84 (C-I' ) , 129.44 (C-2 ' ) , 117.22 (C-31 ) , 163.47a(C-4' ) , 117.22 (C-5 ' ) , 129.44 (C-6 ' ) ,
165.63a(C-2") , 103.23(C-3") , 189.29b (C-4" ) , 162.83a (C-5" ) , 102.93 (C-6") , 162.23a(C-7") , 96.72 (C-8") , 159.80c (C-9" ) ,
103.65(C-IO") , 121.87 (C-I" ' ) , 132.76 (C-2 ' " ) , 125.14 (C-3 ' " ) , 156.71 (C-4' ") , 121.02 (05' " ) , 127.50(06" ') . Compound 4 (ament of lavone)
1H-NMR (Pyridine-d5, 500 MHz) 57.03 (IH, s, H-3) , 6.84 (IH, s, H-6) , 6.79 (IH, d, J=2.0 Hz, H-8) , 8.54 (IH, d, J=2.0 Hz, H-2') , 7.40 (IH, d, J=8.0 Hz, H-5' ) , 7.87 (IH, d, J=7.0 Hz, H- 6' ) , 6.92 (IH, s, H-3") , 6.71(1H, d, J=2.0 Hz, H-6") , 7.89 (2H, d, J=8.5 Hz, H-2' ", H-6' " ) , 7.14 (2H, d, J=8.5 Hz, H- 3' ' ' , H-5' " ) .
13C-NMR (Pyridine-d5, 125 MHz) δ 165.01 (C-2) , 104.44 (C-3) , 183.41(04) , 163.43(05) , 100.34 (06) , 164.95(07) , 95.19(08) ,
158.85(C-9), 105.38(C-IO), 122.08(C-I'), 128.66 (C-2 ' ) , 122.83(03'), 161.66(C-4') , 117.60 (C-5 ' ) , 132.92 (C-6 ' ) , 166.15(02"), 103.92(C-3"), 183.06 (C-4" ) , 162.77 (C-5" ) , 100.14 (C-6") , 164.06(C-7"), 105.61 (C-8") , 156.19 (C-9") , 105.27(C-IO"), 122.76(C-I111), 129.16 (C-2 ' ' ' ) , 117.18 (C-3 ' ' ' ) , 162.98 (C-4' "), 117.18 (C-51 ''), 129.16 (C-6 • ' ' ) . Compound 5 (robustaflavone)
1H-NMR (DMSO-D6, 500 MHz) 56.81 (IH, s, H-3) , 6.48 (2H, br d, J=2.0 Hz, H-6, H-8), 7.82 (IH, br s, H-2 • ) , 7.02 (IH, d, J=8.5 Hz, H-51), 7.90 (IH, dd, J=8.5, 2.5 Hz, H-61), 6.77 (IH, s, H-3"), 6.6O(1H, s, H-8"), 7.96 (2H, d, J=8.5 Hz, H-21 11, H-
611 1), 6.95 (2H, d, J=8.5 Hz, H-3111, H-5111).
13C-NMR (DMSO-D6, 125 MHz) δ 164. lla (C-2) , 102.81b (C-3) , 181.82c(C-4) , 159.09(05), 98.82(06), 163.54(07), 94.04d(C-8), 157.37(09), 103.71(C-IO), 121.28(C-I1), 127.41(02'),
120.54 (C-31 ), 161.47e(C-4') , 116.42 (C-5 ' ) , 130.92(06'), 164.01a(C-2") , 102.75b(C-3") , 181.73C (C-4") , 161.17e (C-5" ) , 103.29(06"), 163.54(07"), 93.73d (C-8" ) , 156.42 (C-9" ) ,
103.71(C-IO"), 121.21(C-I1 1 ') , 128.51(02" '), 116.02(03' "), 161.47e(C-4! ' ' ) , 116.02(05" '), 128.51(06" ') . Compound 6 ( ginkgetin)
1H-NMR (DMSO-D6, 500 MHz) δ 6.88 (IH, s, H-3), 6.36 (IH, d, J=2.2 Hz, H-6), 6.79 (IH, s, H-8), 8.09 (IH, d, J=2.1 Hz, H- 21), 7.36 (IH, d, J=8.6 Hz, H-51), 8.22 (IH, d, J=8.7 Hz, H-
6' ) , 6.99 (IH, s, H-3") , 6.38(1H, s, H-6") , 7.49 (2H, d, J=8.8 Hz, H-2' 1 1, H-6' " ) , 6-78 (2H, d, J=8.8 Hz, H-3' ! I, H- 51 ") - 3.79(s, 3H, OCH3) , 3.88(s, 3H, OCH3)
13C-NMR (DMSO-D6, 125 MHz) 5163.01 (C-2) , 103.7 (C-3) , 181.9MC-4) , 161.09(C-5) , 98.74 (C-6) , 165.22 (C-7) , 92.69(C-8) ,
157.42 (C-9) , 104.43(C-IO) , 122.38 (C-I1 ) , 128.24 (C-2 ' ) ,
121.83(C-3') , 160.66(C-4' ) , 117.60 (C-5 ' ) , 130.92 (C-6 ' ) ,
163.15(C-2") , 102.92(C-3") , 181.06 (C-4") , 160.07 (C-5" ) ,
98.84 (C-6") , 162.06(07") , 103.61 (C-8" ) , 154.19(09") , 103.27 (C-IO") , 121.76(C-I1 1 1) , 127.86(02" ' ) , 115.38 (C-3 ' " ) ,
161.28 (C-41 " ) , 115.59(C-S1 ") , 127.46 (C-6 • " ) . 55.76(OCH3) ,
56.37 (OCH3)
Compound 7 (ochnaf lavone) 1H-NMR (DMSO-D6, 500 MHz) 56.41 (IH, s, H-3) , 6.17 (IH, s,
H-6) , 6.37 (IH, s, H-8), 7.82 (IH, s, H-2 ' ) , 7.01 (IH, d, J=7.2 Hz, H-51 ) , 7.56 (IH, d, J=I .2 Hz, H-6' ) , 6.52 (IH, s, H- 3") , 6.35(1H, s, H-6") , 6.75(1H, s, H-8") , 7.48 (2H, d, J=8.2 Hz, H-2' ", H-6" ') , 6.72 (2H, d, J=8.2 Hz, H-3" ', H-5' " ) . 13C-NMR (DMSO-D6, 125 MHz) 5164.02 (C-2) , 103.60 (C-3) ,
182.21(04) , 161.74(05) , 98.32(06) , 165.02(07), 94.30(08), 157.78 (09) , 103.59* (C-IO) , 122.33(C-I' ) , 121.22 (C-2 ' ) ,
141.5KC-31) , 153.56(04' ) , 117.92 (C-5 ' ) , 125.35 (C-61 ) ,
162.62 (C-2") , 104.15(03") , 181.23 (C-4") , 161.59 (C-5") ,
99.1MC-6"), 164.59(C-7"), 94.32 (C-8") , 157.53(09"), 103.39*(C-10"), 124.29(C-I'"), 127.91(02'"), 116.64(C-S1 1'), 160.57 (C-41 ''), 116.74 (C-51 "), 128.41 (C-6 " ' ) .
Experimental Example 1: Procollagen biosynthesis
Fibroblasts separated from human skin were inoculated in a 24-well plate by 106 cells/well, followed by culture until they grew 90%. Then, the cells were cultured in a serum-free medium for 24 hours. 4-substituted benzoic acid derivative compound having 3, 4-methylenedioxy or 3, 4-ethylenedioxybenzene moiety, obtained in Examples 1-2, was dissolved in the serum- free medium was treated thereto at the concentration of 10~4, followed by culture in a CO2 incubator for 24 hours. Supernatant was separated and procollagen level was measured using procollagen type 1 ELISA kit. The results are shown in Table 1 and the biosynthesis capacity was presented by the ratio to non-treated group (considered as 100%) . [Table 1]
Experimental Example 2: Collaqenase (MMP-I) inhibitory activity
Human fibroblasts were inoculated in a 96-well microtiter plate containing DMEM (Dulbecco's Modified Eagle's Media) supplemented with 2.5% FBS at the concentration of 5,000 cells/well, followed by culture till the cells grew 70-80%. The sample compound was treated thereto at the concentration of 10"4 for 24 hours and then the cell culture solution was collected. Collagenase production in the cell culture solution was measured by using a commercial collagenase measuring kit (Catalog #: RPN 2610, Amersham Pharmacia, USA). First, the collected cell culture solution was loaded in a 96-well plate evenly distributed with the first collagenase antibody, followed by antigen-antibody reaction in a thermostat for 3 hours. Three hours later, the chromophore-conjugated second collagen antibody was added to the 96-well plate, followed by reaction for 15 minutes. 15 minutes later, coloring material was added thereto to induce color development for 15 minutes at room temperature and then the reaction was terminated by adding IM sulfuric acid. The reaction solution was yellow. According to the degree of the reaction, the degree of yellow
color varied, optical density^s (OD405) of the yellow 96-well plate was measured by using a spectrophotometer and collagenase production was calculated by mathematical formula 1. At this time, the OD of the cell culture solution not- treated with the sample compound was considered as control.
[Mathematical Formula 1]
Collagenase Expression Level (%) = (OD of the group treated with the sample compound/0D of control) XlOO
[Table 2]
As shown in Table 2, the biflavonoid derivatives were proved to have inhibitory effect on matrix metallo protease (MMP-I) .
Experimental Example 3: Improvement effect on wrinkles caused by UV
To investigate anti-aging effect of the anti-wrinkle material of the present invention on wrinkles caused by UV, the biflavonoid derivatives were dissolved in a vehicle
(propylene glycol :ethanol: water = 5:3:2 (v/v) ) at the concentration of 1%. 6-week old female SKH-I hairless mice were divided into 4 experimental groups and 1 control group
(10 mice per group) . UV was irradiated to the mice from 70 cm distance three times a week for 10 weeks (total 30 times) to cause wrinkles. The sample material and the positive control material were transdermally administered by 100 μL, twice a day (morning/afternoon) , 5 days a week (Monday - Friday) for
10 weeks. This administration started simultaneously with the wrinkle inducing irradiation. Skin replica was taken to evaluate anti-wrinkle effect.
As the experimental materials, 3 fractions and biflavonoid fraction (BFF) that exhibited particularly high procollagen biosynthesis capacity and collagenase expression inhibiting activity were selected and the results are shown in Fig. 1.
As shown in Fig. 1, when biflavonoid derivatives were administered, anti-wrinkle effect was significant, compared with when only a vehicle was administered. The formulation forms of a cosmetic composition for improving wrinkles containing biflavonoid derivatives (sumaflavone, 2' , 8"-biapigenin, taiwaniflavone, amentoflavone, robustaflavone, ginkgetin and ochnaflavone) can be selected at random from the group consisting of nutritional cream,
nutritional lotion, massage cream, nutritional essence, and softener, etc.
Manufacturing Example 1: Nutritional toner (milk lotion) Nutritional toner containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
Manufacturing Example 2: Softener (skin lotion)
Softener containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
Manufacturing Example 3: Nutritional cream
Nutritional cream containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
Manufacturing Example 4: Massage cream
Massage cream containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
Manufacturing Example 5: Pack
Pack containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in the below table.
Manufacturing Example 6: Gel
Gel containing biflavonoid derivatives was prepared by the conventional method according to the composition shown in
the below table.
[industrial Applicability] As explained hereinbefore, the biflavonoid derivatives of the present invention interact with biflavonoid receptor to increase procollagen biosynthesis, so that they can have the effect of inhibiting wrinkle generation caused by lack of skin elasticity resulted from the denaturation of collagen, one of the important skin components, and of inhibiting the expression of collagenase, the enzyme decomposing collagen, and thereby increases improvement of wrinkles caused by UV. Therefore, the cosmetic composition containing the biflavonoid derivatives as an active ingredient of the present invention can be effectively used as a cosmetic composition or an agent for improvement and prevention of wrinkles without side effects .
Claims
[CLAIMS]
[Claim l]
A cosmetic composition for improving skin wrinkles containing biflavonoid derivatives as an active ingredient.
[Claim 2]
The cosmetic composition for improving skin wrinkles according to claim 1, wherein the biflavonoid derivatives are extracted from natural medicinal herbs or plants such as Selaginella tamariscina, Ginkgo biloba, Cephalotaxus koreana,
Nandina domestica and Lonicera japonica.
[Claim 3]
The cosmetic composition for improving skin wrinkles according to claim 2, wherein the biflavonoid derivatives are obtained from ethyl acetate after adding ethyl acetate and water to methanol extract of the medicinal herbs.
[Claim 4] The cosmetic composition for improving skin wrinkles according to claim 3, wherein the biflavonoid derivatives are represented by formulas 1-7. <Formula 1>
[Claim 5] The cosmetic composition for improving skin wrinkles according to claim 4, wherein the biflavonoid derivatives increase procollagen biosynthesis.
[claim 6] The cosmetic composition for improving skin wrinkles according to claim 4, wherein the bioflavonoid derivatives inhibit the expression of collagenase.
[Claim 7] The cosmetic composition for improving skin wrinkles according to claim 4, wherein the biflavonoid derivatives improve wrinkles caused by UV.
[Claim 8]
The cosmetic composition for improving skin wrinkles according to claim 4, wherein the content of the biflavonoid derivatives is 0.001 - 10 weight% for the total weight of the composition.
[Claim 9]
The cosmetic composition for improving skin wrinkles according to claim 4, wherein the content of the biflavonoid derivatives is 0.01 - 5 weight% for the total weight of the composition.
[Claim 10]
The cosmetic composition for improving skin wrinkles according to one of claims 1 - 3, wherein the cosmetic composition can be formulated as softener, astringent, nutritional toner, nutritional cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, body oil, gel and body essence.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200880018472A CN101730520A (en) | 2007-06-01 | 2008-02-22 | The external preparation for skin anti-wrinkle composition that contains two Flavoneoid derivatives |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2007-0053700 | 2007-06-01 | ||
KR1020070053700A KR100902173B1 (en) | 2007-06-01 | 2007-06-01 | Anti-wrinkle composition for external applications to the skin containing Biflavonoid derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008147022A1 true WO2008147022A1 (en) | 2008-12-04 |
Family
ID=40075221
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2008/001038 WO2008147022A1 (en) | 2007-06-01 | 2008-02-22 | Anti-wrinkle composition for external applications to the skin containing biflavonoid derivatives |
Country Status (3)
Country | Link |
---|---|
KR (1) | KR100902173B1 (en) |
CN (1) | CN101730520A (en) |
WO (1) | WO2008147022A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010090001A1 (en) * | 2009-02-09 | 2010-08-12 | 株式会社資生堂 | Skin-whitening agent, anti-aging agent, and anti-oxidant agent |
US10251832B2 (en) | 2017-05-26 | 2019-04-09 | Mary Kay Inc. | Cosmetic compositions and methods |
CN115894424A (en) * | 2023-01-06 | 2023-04-04 | 中日友好医院(中日友好临床医学研究所) | Novel biflavonoid compound and preparation method, pharmaceutical composition and application thereof |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101117561B1 (en) * | 2008-12-09 | 2012-02-29 | 주식회사 코리아나화장품 | Cosmetic Composition for Anit-Aging Comprising Flavonoid as Active Ingredients |
KR20120009953A (en) * | 2010-07-23 | 2012-02-02 | (주)아모레퍼시픽 | Composition containging amentoflavone for preventing uv-induced skin cell damage |
KR102046331B1 (en) * | 2013-10-10 | 2019-11-19 | 주식회사 엘지생활건강 | Cosmetics or pharmaceutical composition containing magnolol or hinokiflavone for skin volume augmentation and anti-wrinkle |
KR102196952B1 (en) * | 2018-12-27 | 2020-12-30 | 광주여자대학교 산학협력단 | Composition for Promoting Skin Regeneration Containing Extract of Nandina domestica Leaf |
KR102335262B1 (en) * | 2019-09-26 | 2021-12-07 | 한국생명공학연구원 | Cosmetic composition for preventing skin aging and improving skin winkle comprising extracts of Selaginella rossii |
KR102316415B1 (en) * | 2019-11-22 | 2021-10-21 | 광주여자대학교 산학협력단 | manufacturing method of cosmetic composition using Nandina domestica Thunb |
KR102316407B1 (en) * | 2019-11-22 | 2021-10-21 | 광주여자대학교 산학협력단 | cosmetic composition using Nandina domestica Thunb |
CN115778866A (en) * | 2022-12-29 | 2023-03-14 | 云南大学 | Application of Cephalotaxus fortunei extract in cosmetics or preparing medicines |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100561036B1 (en) * | 2004-04-30 | 2006-03-20 | 한불화장품주식회사 | Skin external preparation composition containing the extract of Seol and Kwonbaek as an active ingredient |
KR20070013622A (en) * | 2005-07-26 | 2007-01-31 | 에스케이케미칼주식회사 | Cosmetic composition for skin anti-aging |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100408020C (en) * | 2002-10-23 | 2008-08-06 | 吴凤锷 | Skin-care cosmetic article for neck |
-
2007
- 2007-06-01 KR KR1020070053700A patent/KR100902173B1/en active IP Right Grant
-
2008
- 2008-02-22 CN CN200880018472A patent/CN101730520A/en active Pending
- 2008-02-22 WO PCT/KR2008/001038 patent/WO2008147022A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100561036B1 (en) * | 2004-04-30 | 2006-03-20 | 한불화장품주식회사 | Skin external preparation composition containing the extract of Seol and Kwonbaek as an active ingredient |
KR20070013622A (en) * | 2005-07-26 | 2007-01-31 | 에스케이케미칼주식회사 | Cosmetic composition for skin anti-aging |
Non-Patent Citations (1)
Title |
---|
LEE M. ET AL.: "Osteoblast differentiation stimulating activity of biflavonoids from Cephalotaxus koreana", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 16, no. 11, 1 June 2006 (2006-06-01), pages 2850 - 2854, XP025106132, DOI: doi:10.1016/j.bmcl.2006.03.018 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010090001A1 (en) * | 2009-02-09 | 2010-08-12 | 株式会社資生堂 | Skin-whitening agent, anti-aging agent, and anti-oxidant agent |
JP2010180189A (en) * | 2009-02-09 | 2010-08-19 | Shiseido Co Ltd | Skin whitening agent, anti-aging agent, and antioxidant |
TWI466686B (en) * | 2009-02-09 | 2015-01-01 | Shiseido Co Ltd | Whitening agents, anti-aging agents and antioxidants, and whitening endermic agents, anti-aging and anti-skin external oxidation method for producing a skin external preparation of |
US9364423B2 (en) | 2009-02-09 | 2016-06-14 | Shiseido Company, Ltd. | Whitening agent, anti-aging agent, and antioxidant agent |
US10251832B2 (en) | 2017-05-26 | 2019-04-09 | Mary Kay Inc. | Cosmetic compositions and methods |
US10881603B2 (en) | 2017-05-26 | 2021-01-05 | Mary Kay Inc. | Cosmetic compositions and methods |
US11534391B2 (en) | 2017-05-26 | 2022-12-27 | Mary Kay Inc. | Cosmetic compositions and methods |
CN115894424A (en) * | 2023-01-06 | 2023-04-04 | 中日友好医院(中日友好临床医学研究所) | Novel biflavonoid compound and preparation method, pharmaceutical composition and application thereof |
CN115894424B (en) * | 2023-01-06 | 2023-05-12 | 中日友好医院(中日友好临床医学研究所) | Novel biflavanoid compound, preparation method, pharmaceutical composition and application thereof |
Also Published As
Publication number | Publication date |
---|---|
KR20080105730A (en) | 2008-12-04 |
CN101730520A (en) | 2010-06-09 |
KR100902173B1 (en) | 2009-06-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2008147022A1 (en) | Anti-wrinkle composition for external applications to the skin containing biflavonoid derivatives | |
JP2020532560A (en) | Cosmetic composition containing extract of Dendrobium candidam flower | |
AU2012208626B2 (en) | Monoterpene derivatives of chalcone or dihydrochalcone and their use as depigmenting agents | |
JP2007223919A (en) | Skin cosmetic | |
AU2012208626A1 (en) | Monoterpene derivatives of chalcone or dihydrochalcone and their use as depigmenting agents | |
WO2016110276A1 (en) | Topical composition containing obakunone and skin-whitening method using same | |
KR101590965B1 (en) | Composition for skin-whitening comprising oxyresveratrol and dioscin | |
KR101758144B1 (en) | Composition for anti-aging containing youngia denticulata extract | |
KR101050484B1 (en) | Skin whitening composition containing lactone compound as an active ingredient | |
JP5275075B2 (en) | (2Z, 8Z) -Composition for whitening skin containing methylicaria acid methyl ester as an active ingredient | |
KR101500551B1 (en) | Cosmetic composition with hydroxycitric acid for skin whitening | |
KR20210134589A (en) | Composition for improving skin comprising an extract of Pueraria thomsonii or a compound derived therefrom | |
KR101317433B1 (en) | The cosmetic composition for skin whitening comprising the mixture of extract of Hovenia dulcia, Platycodon grandiflorum, wheat bud and sage | |
KR101721666B1 (en) | Skin-whitening compound from Inula britannica, and skin-whitening composition containing the same | |
KR20150025984A (en) | Composition for promoting hair growth or restoration containing 21-o-angeloyltheasapogenol e3 | |
KR20170013588A (en) | Composition for skin whitening and anti-wrinkle comprising Cistanche deserticola extract as effective component | |
KR20190033871A (en) | Complex cosmetic composition for improving skin-aging | |
KR101176524B1 (en) | Cosmetic Composition for Anti-Aging Comprising Flavonoid as Active Ingredients | |
KR101870210B1 (en) | Anti-aging composition comprising aster plant extracts | |
KR20180061662A (en) | Composition for skin improvement containing anemoside A3 | |
KR101784759B1 (en) | Cosmetic composition with irigenin for skin whitening | |
KR20100001167A (en) | Cosmetic composition comprising quercitrin and/or myricitrin as active ingredients | |
JP2010111645A (en) | Skin-lightening agent and skin cosmetic product | |
JPWO2005027904A1 (en) | Hair restorer | |
KR101042005B1 (en) | Compound from Lindera erythrocarpa, method for isolating thereof, and composition for skin whitening comprising the same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200880018472.2 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 08723076 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 08723076 Country of ref document: EP Kind code of ref document: A1 |