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WO2017213346A1 - Composition contenant de la diosmine ou son sel comme ingrédient actif et présentant un effet d'amélioration de l'hydratation de la peau, d'exfoliation de la peau, de renforcement de l'élasticité de la peau, d'inhibition de l'érythème, de réduction des rides de la peau, ou de retardement du photovieillissement de la peau - Google Patents

Composition contenant de la diosmine ou son sel comme ingrédient actif et présentant un effet d'amélioration de l'hydratation de la peau, d'exfoliation de la peau, de renforcement de l'élasticité de la peau, d'inhibition de l'érythème, de réduction des rides de la peau, ou de retardement du photovieillissement de la peau Download PDF

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Publication number
WO2017213346A1
WO2017213346A1 PCT/KR2017/004231 KR2017004231W WO2017213346A1 WO 2017213346 A1 WO2017213346 A1 WO 2017213346A1 KR 2017004231 W KR2017004231 W KR 2017004231W WO 2017213346 A1 WO2017213346 A1 WO 2017213346A1
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WIPO (PCT)
Prior art keywords
skin
diosmin
composition
improvement
photoaging
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PCT/KR2017/004231
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English (en)
Korean (ko)
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박태선
Original Assignee
연세대학교 산학협력단
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Publication of WO2017213346A1 publication Critical patent/WO2017213346A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • 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
    • A61K8/67—Vitamins
    • 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
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • 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
    • 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
    • A61K8/9706—Algae
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat

Definitions

  • the present invention relates to a composition containing diosmin or a salt thereof as an active ingredient, and more particularly, to enhance skin moisture content, decrease skin moisture evaporation amount, increase procollagen secretion amount, promote collagen biosynthesis, inhibit collagen fiber damage, collagen fiber degradation
  • Cosmetic composition having the effect of improving skin moisturizing, removing dead skin cells, enhancing skin elasticity, inhibiting erythema, improving skin wrinkles and / or improving skin photoaging by using diosmin or a salt thereof that inhibits, inhibits erythema and thickening of the skin epidermal layer.
  • Dietary supplements, pharmaceuticals and quasi-drug compositions can be provided.
  • the skin is composed of three layers: epidermis, dermis, and hypodermis.
  • the epidermis especially the stratum corneum, the outermost layer of the epidermis, acts as a barrier to the skin to lose water and electrolytes.
  • the dermal layer plays a role in maintaining the elasticity of the skin and supporting the structure through collagen and elastin synthesis.
  • collagen and elastin are major proteins produced in fibroblasts and are involved in skin mechanical firmness, tissue binding strength and elasticity.
  • Collagen forms various isoforms according to its shape and structural features, and there are a total of 28 collagen isotypes in human tissues, of which collagen is present in Type 1, 3. 4. 6. 13, 14, 17 and the like are known.
  • Collagen types 1 and 3 make up the interstitial components of the dermal layer
  • collagen type 7 is the major component of the dermal and epidermal junctions.
  • Type I collagen is the largest amount of extracellular matrix protein in the skin connective tissue, and there are other proteins such as elastin, fibronectin, integrin, fibrillin, and proteoglycan.
  • the newly synthesized procollagen is secreted into the extracellular space of skin cells through an enzymatic reaction to form a microfibril of triple helix configuration, and the microfibrils are leucine-rich small proteoglycans (leucine). It combines with rich small proteoglycans to form fibrils. As a result, the fibrils thus formed form collagen fibers that provide skin binding and elasticity.
  • Skin aging is known to decrease collagen content, a protein that accounts for most of the collagen of skin dermis. Collagen decreases the skin's tension and strength. have.
  • Skin aging is largely divided into endogenous aging due to physiological aging and photoaging caused by continuous ultraviolet radiation (UV) exposure. Repeated ultraviolet exposure results in increased collagen degrading enzymes and causing denaturation and destruction of collagen fibers, reducing the elasticity of the skin and promoting the production of wrinkles. That is, the generation of reactive oxygen species (ROS) is increased in skin tissues exposed to ultraviolet rays continuously, and the latter has a signaling system mediated by growth factor receptor (EGF-R), tumor necrosis factor (TNF) -receptor, etc. It promotes proinflammatory cytokine production.
  • EGF-R growth factor receptor
  • TNF tumor necrosis factor
  • Activation of these receptors consists of continuous phosphorylation that activates downstream signaling mediators, including mitogen-activated protein kinase (MAPK), resulting in activator protein-1 (AP-1). And activating transcription factors such as nuclear factor ⁇ B (NF- ⁇ B) to induce an inflammatory response and to promote the activity of collagenase such as matrix metalloproteinases (MMPs) to reduce skin elasticity and promote wrinkle formation do.
  • AP-1 regulates the expression of numerous genes involved in cell growth and differentiation and strongly regulates the expression of some MMPs.
  • MMP-1 is known as collagenase 1, and is based on type 1 and 3 collagen.
  • diosmin is the main component of the drug that is commercially available for the treatment of diseases such as chronic venous insufficiency, hemorrhoids, lymphedema. It is generally recommended to take 500 mg diosmin tablets twice a day for the treatment of these diseases.In acute illnesses, 1,000 mg three times a day and 1,000 mg twice daily for three days. After that, it is recommended to take 500 mg twice a day for two months.
  • Diosmin is also very effective in relieving hemorrhoidal symptoms associated with pregnancy and has no negative effect on the maintenance of pregnancy, fetal development, birth weight, neonatal growth rate and intake, and does not mutate or affect reproductive function. Turned out to be.
  • Diosmin has an effect on the lymphatic system to increase the lymph flow (lymph flow).
  • lymph flow lymph flow
  • diosmin for the treatment of upper limb lymphedema has been shown to improve symptoms.
  • Diosmin also showed significant symptomatic relief in lymphedema animal models such as burns and lung cotusions.
  • Diosmin has been shown to be effective in premenstrual syndrome, viral infections, mastopathy, colitis, etc. In addition, diosmin has been shown to have anti-cancer effects and cell proliferation inhibitory effects in various animal and cell line models. . However, there is no report on the anti-wrinkle or collagen promoting activity of diosmin.
  • the present inventors conducted a study to develop a food or cosmetic material that is effective in improving wrinkles by inhibiting the action of collagen degrading enzymes in natural products with fewer side effects and promoting collagen synthesis, and thus, diosmin improves skin moisturization.
  • the present invention was completed by confirming that exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement were shown.
  • An object of the present invention is to provide a cosmetic composition having an effect of improving skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging.
  • Another object of the present invention is to provide a health functional food composition having an effect of improving skin moisturizing, removing skin dead skin, enhancing skin elasticity, suppressing erythema, improving skin wrinkles and / or improving skin photoaging.
  • Still another object of the present invention is to provide a pharmaceutical or quasi-drug composition having the effect of improving skin moisturizing, removing skin dead skin, enhancing skin elasticity, suppressing erythema, improving skin wrinkles and / or improving skin photoaging.
  • the present invention provides a skin moisturizing improvement, skin exfoliation, skin elasticity enhancement, erythema suppression, wrinkle improvement and / or skin comprising administering a composition containing diosmin or a pharmaceutically acceptable salt thereof as an active ingredient It is intended to provide a method for improving photoaging.
  • the present invention comprises diosmin or a pharmaceutically acceptable salt thereof as an active ingredient for improving skin moisturizing, skin exfoliation, skin elasticity, erythema suppression, skin wrinkle improvement and / or preparation of skin photoaging improving agent. It is intended to provide a use of the composition.
  • the present invention provides a cosmetic composition having a skin moisturizing improvement, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement effect including diosmin or a cosmetically acceptable salt thereof as an active ingredient. to provide.
  • composition containing the diosmin of the present invention or a salt thereof as an active ingredient may improve skin moisture content, reduce skin moisture evaporation amount, increase collagen secretion amount, promote collagen biosynthesis, inhibit collagen fiber damage, inhibit collagen fiber degradation, inhibit erythema and skin epidermal layer. It has excellent thickening inhibitory activity, so it can be usefully used to improve skin moisturizing, skin exfoliation, skin elasticity improvement, erythema suppression, skin wrinkle improvement and / or skin photoaging.
  • the diosmin of the present invention is a natural product, it is safe for the human body and has less side effects, and thus may be used in various materials such as cosmetics, health foods, medicines or quasi-drugs.
  • 1 is a graph showing the results of measuring procollagen secretion by ELISA assay after irradiating UVB at 20 mJ / cm 2 to human dermal fibroblasts for 24 hours with 100 ⁇ M of vitamin C or diosmin (-UVB: Normal group without UVB treatment, + UVB: UVB treated control group, DM: UVB treated group, diosmin treated group, VitC: UVB treated group, vitamin C treated group, DM + VitC: UVB treated group Then treated with diosmin and vitamin C).
  • Figure 2 is a graph showing the weight gain and dietary intake of mice fed the experimental diet having the composition of Table 1 (A: weight, B: weight gain, C and D: diet intake).
  • Figure 3 is a graph showing the water content (A), water evaporation (B), elasticity (C) and erythema index (D) of the skin tissue of mice fed the experimental diet having the composition of Table 1.
  • Figure 4 is a photograph showing the back skin tissue of each mouse fed the experimental diet having the composition of Table 1.
  • FIG. 5 is a photograph (A) and a graph (B) showing the degree of wrinkle formation of the back skin tissue of the mouse fed the experimental diet having the composition of Table 1.
  • FIG. 6 is a graph (A) and skin epidermal layer photograph (B) of measuring skin thickness of mice fed an experimental diet having the composition of Table 1.
  • FIG. 6 is a graph (A) and skin epidermal layer photograph (B) of measuring skin thickness of mice fed an experimental diet having the composition of Table 1.
  • Figure 7 is a photograph observing the change in the amount and morphology of collagen fibers in mice fed an experimental diet having the composition of Table 1.
  • FIG. 8 shows the results of RT-PCR measurement of expression changes of collagen and MMP genes in hairy mouse back tissue treated with diosmin.
  • diosmin has been known to be effective in treating diseases such as chronic venous insufficiency, hemorrhoids and lymphedema, premenstrual syndrome, viral infections, breast pain, colitis, etc.
  • diseases such as chronic venous insufficiency, hemorrhoids and lymphedema, premenstrual syndrome, viral infections, breast pain, colitis, etc.
  • moisturizing, skin exfoliation, skin elasticity improvement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement has been no report on moisturizing, skin exfoliation, skin elasticity improvement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement.
  • the present inventors confirmed the novel activity of diosmin related to skin health, and developed a cosmetic composition, a dietary supplement, a pharmaceutical and a quasi-drug composition containing diosmin or a salt thereof as an active ingredient.
  • the composition provided by the present invention has excellent skin hydration content, reduced skin moisture evaporation amount, increased procollagen secretion, increased collagen biosynthesis, inhibited collagen fiber damage, inhibited collagen fiber degradation, erythema suppression and thickening inhibitory effect of skin epidermal layer. It can be usefully used for improvement, skin moisturizing improvement, skin exfoliation, skin elasticity improvement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement.
  • the present invention is a cosmetic composition having a skin moisturizing improvement, skin exfoliation, skin elasticity enhancement, erythema suppression, wrinkle improvement and / or skin photoaging improvement effect containing diosmin or a cosmetically acceptable salt thereof as an active ingredient To provide.
  • Diosmin is a flavonoid glycoside (flavone) -based compound represented by Formula 1 below, and the name designated by the International Pure and Applied Chemistry Organization (IUPAC) is 5-hydroxy-2- (3-hydroxy-4 -Methoxyphenyl) -7-[(2S, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy-6-[[(2R, 3R, 4R, 5R, 6S) -3,4 , 5-trihydroxy-6-methyloxan-2-yl] oxymethyl] oxan-2-yl] oxychromen-4-one [5-Hydroxy-2- (3-hydroxy-4-methoxyphenyl) -7 -[(2S, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy6-[[(2R, 3R, 4R, 5R, 6S) -3,4,5-trihydroxy-6-methyloxan-2- yl] oxymethyl] oxan-2-yl]
  • diosmin is well soluble in water and in small amounts in dimethyl sulfoxide (50 mg / ml at 25 ° C) and ethanol ( ⁇ 1 mg / ml at 25 ° C).
  • the melting point of diosmin is 274 ° C, the boiling point is 926.8 ° C (at 760 mmHg), the density is 1.7 g / cm3, the refractive index is n20D 1.71, and the pKa value is: 6.1.
  • Diosmin is a flavonoid glycoside material present in various plants and can be extracted from plants or synthesized from flavonoid hesperidin.
  • the particularly unripe Meyer lemon (3.06 g diosmin / 100 g of dry weight) and Buddha's finger fruits (3.64 g / 100 g of dry weight) contain the highest amount of diosmin Known as
  • Vetches (Asian and Caucasian vetch species) native to North America, Europe, Africa, and Asia are representative plants containing a large amount of diosmin, and the leaves contain about 2% of diosmin.
  • Herb hyssop also called Hyssopus officinalis or Hyssopus decumbens
  • native to southern and central Asia is also a source of diosmin, especially in leaves and flowers.
  • the method for obtaining the diosmin of the present invention is not particularly limited, and may be isolated from natural products, chemically synthesized using a known production method, or commercially available.
  • diosmin Although the LD 50 value of diosmin is not known much, it has been reported that it is safe to administer more than 3000 mg / kg when administered orally to mice. Diosmin has also been reported to be very limited in migration through the placenta and into breast milk.
  • diosmin is administered at 100 mg / kg to 3,000 mg / kg, preferably 500 mg / kg to 2,000 mg / kg, the toxicity is very low or not, so cosmetic compositions, dietary supplement compositions, pharmaceutical or quasi-drug compositions, etc. Can be used as
  • the diosmin may include a diosmin hydrate, a diosmin derivative, and the like within a range having the same efficacy, and may include a solvate or stereoisomer thereof.
  • the term "improve skin wrinkles” means maintaining or enhancing the ability to be associated with wrinkles and elasticity of the skin.
  • Collagen (collagen) and elastic fiber elastin (collagen) in the dermal layer of the skin is the main protein that plays a role in the skin elasticity, collagen biosynthesis is affected by the internal and external skin.
  • the skin cells are reduced in cell activity due to natural aging, the collagen fibers are reduced, or the active oxygen produced by excessive irradiation of ultraviolet rays or stress as an external factor, the thiol group of the protein (thiol: -SH)
  • the enzyme activity or by increasing the expression of degradation enzymes, such as collagen, elastin, increase the wrinkles of the skin and decrease the elasticity, the skin aging progresses.
  • the terms "cosmetic acceptable salt”, “food acceptable salt”, “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by free acid.
  • Acid addition salts can be prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile.
  • a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile.
  • equimolar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.
  • an inorganic acid or an organic acid may be used as the free acid.
  • the inorganic acid may be hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like, which may be used alone or in combination of two or more.
  • Non-limiting examples of the organic acid are methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid (propionic acid).
  • acid citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid (glucuronic acid), aspartic acid, ascorbic acid, carbonic acid, vanic acid, hydroiodic acid and the like can be used. These may be used alone or in combination of two or more thereof.
  • the diosmin may use a base to make a cosmetically or food acceptable metal salt.
  • Alkali metal or alkaline earth metal salts can be obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compounds salt, and then evaporating and drying the filtrate.
  • the metal salt it is particularly preferable to prepare sodium, potassium or calcium salts, but is not limited thereto.
  • Corresponding silver salts can also be obtained by reacting an alkali or alkaline earth metal salt with a suitable silver salt (eg silver nitrate).
  • the salts of diosmin may include all salts of acidic or basic groups which may be present in the compound of diosmin unless otherwise indicated.
  • the salt of the diosmin may include sodium, calcium and potassium salts of the hydroxy group, and other cosmetically acceptable salts of the amino group include hardbromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, and the like. It can be prepared through the method.
  • the effective amount of diosmin or its cosmetically acceptable salt in the cosmetic composition of the present invention is not particularly limited, and may be included in 0.0001 to 20% by weight based on the total weight of the composition. Less than 0.0001% by weight of diosmin or its salt in the cosmetics may have a small amount of anti-wrinkle effect, and more than 20% by weight of diosmin or its salt may exhibit known toxicity.
  • the procollagen type I C-peptide (PIP) secretion was increased when compared to the control cells irradiated with ultraviolet rays only when treated with diosmin in the human dermal fibroblasts irradiated with ultraviolet rays (Fig. 1).
  • FIG. 4 significantly reduces skin wrinkle area, depth and length, significantly inhibiting wrinkle formation
  • FIG. 5 The thickness of the epidermal layer thickened by this was also significantly reduced (FIG. 6), and the effect of densifying collagen fibers and maintaining the arrangement regularly (FIG. 7), significantly reducing the expression of collagen types 1 ⁇ 1, 1 ⁇ 2 and 3 ⁇ 1.
  • the composition comprising the diosmin of the present invention or a salt thereof is a functional cosmetic that provides an effect of improving skin wrinkles, improving skin moisturizing, removing skin dead skin, enhancing skin elasticity, inhibiting erythema, improving skin wrinkles and / or skin photoaging, It can be usefully used as a material for health functional food, medicine or quasi-drugs.
  • the term "cosmetic composition” is a composition comprising the compound, the formulation may be in any form.
  • the cosmetic preparation prepared using the composition may be a nourishing cream, eye cream, massage cream, cream such as cleansing cream, pack, lotion such as nutrient lotion, essence, softening lotion, and lotion such as nourishing lotion.
  • Powders, foundations, makeup bases, and the like and may be prepared and commercialized in any of these formulations to achieve the object of the present invention, and are not limited to the above examples.
  • the cosmetic composition according to the present invention can be formulated by a conventional cosmetic preparation method.
  • the cosmetics of the present invention include skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, pack, mask pack, mask sheet It may be one having a formulation selected from the group consisting of, soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder and eye shadow.
  • the cosmetic composition of the present invention may include other additives such as excipients, carriers, etc. in addition to diosmin or salts thereof, and it is possible to apply and formulate as needed the usual ingredients to be used in general skin cosmetics.
  • the cosmetic composition of the present invention may further include a transdermal penetration enhancer.
  • transdermal penetration enhancer is a composition that allows a desired component to penetrate into the blood vessel cells of the skin at a high absorption rate.
  • phospholipid components, liposome components and the like used in lecithin cosmetics are included, but are not limited to these.
  • oil which can be mainly used as an oil phase component
  • one or more selected from vegetable oil, mineral oil, silicone oil and synthetic oil can be used. More specifically, mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitis binifera seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, dimethicone Chicon, cyclopentasiloxane, sunflower seed oil and the like can be used.
  • a surfactant may be used conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, phospholipids, and the like, specifically, sorbitan sesquinolate, polysorbate 60 , Glyceryl stearate, lipophilic glyceryl stearate, sorbitan oleate, sorbitan stearate, die-cetyl phosphate, sorbitan stearate / sucrosecoate, glyceryl stearate / polyethylene glycol-100 Stearate, ceteareth-6 oleate, arachidyl alcohol / behenyl alcohol / arachidyl glucoside, polypropylene glycol-26-butes-26 / polyethylene glycol-40 hydrogenated castor oil, etc.
  • surfactants may be used conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric
  • alcohols having 12 to 20 carbon atoms such as cetyl alcohol, stearyl alcohol, octyldodecanol, isostearyl alcohol, etc. may be used alone or in combination of one or more thereof.
  • the aqueous phase component may further add 0.001 to 5% by weight of one or more thickeners such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate and the like to adjust the viscosity or hardness of the aqueous phase.
  • thickeners such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate and the like to adjust the viscosity or hardness of the aqueous phase.
  • the cosmetic composition of the present invention if necessary, active ingredients such as higher fatty acids, vitamins, sunscreens, antioxidants (butylhydroxyanisole, propyl gallic acid, elixolic acid, tocopheryl acetate, butylated hydroxy) Toluene), preservatives (methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinylurea, chlorphenesin, etc.), colorants, pH adjusters (triethanolamine, citric acid, citric acid, sodium citrate, malic acid, Sodium malic acid, fmaric acid, sodium pramate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, etc., moisturizers (glycerine, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin , Betaine, glycerin-26, methylgluse-20 and the like), lubric acid,
  • the cosmetic composition of the present invention further comprises a substance capable of auxiliaryly providing essential nutrients to the skin, and may preferably contain auxiliary agents including, but not limited to, natural flavors, cosmetic flavors, or herbal medicines. have.
  • the cosmetic composition of the present invention may further comprise a skin wrinkle improvement component or skin elasticity enhancing component.
  • the specific skin wrinkle improving component or skin elasticity enhancing component may be any one or more selected from the group consisting of vitamin C, retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract, most preferably Vitamin C.
  • the amount of collagen is measured to a higher value than the case of treating diosmin or vitamin C alone, synergistic effect It was confirmed that it is shown (Fig. 1).
  • the present invention also provides a health function having a skin moisturizing improvement, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement effect, which contain diosmin or a food acceptable salt thereof as an active ingredient.
  • a health function having a skin moisturizing improvement, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement effect, which contain diosmin or a food acceptable salt thereof as an active ingredient.
  • a food composition having a skin moisturizing improvement, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement effect.
  • the term "health functional food” refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functions for the human body.
  • 'functional' means to obtain a useful effect for health purposes such as nutrient control or physiological action on the structure and function of the human body.
  • the health functional food of the present invention can be prepared by a method commonly used in the art, and the preparation can be prepared by adding raw materials and ingredients commonly added in the art.
  • the formulation of the health functional food can also be prepared without limitation as long as the formulation is recognized as a health functional food.
  • the health functional food composition of the present invention has the advantage that there is no side effect that can occur when taking long-term use of the drug, unlike foods as a raw material, and excellent portability, improve skin moisturizing, skin exfoliation, skin elasticity Ingestion may be taken as an adjuvant to promote erythema suppression, skin wrinkle improvement and / or skin photoaging improvement.
  • the dietary supplement composition of the present invention may be prepared in any one formulation selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings.
  • Health functional food composition according to the present invention may be formulated in the form of powder, liquid, tablets, soft capsules, granules, tea bags, instant tea or drink by including diosmin as an active ingredient.
  • the content of diosmin as an active ingredient can be suitably determined according to the purpose of use (prevention or improvement).
  • the amount of diosmin included in the nutraceutical composition may be added to 0.1 to 90% by weight of the total food weight. However, in the case of prolonged intake for health and hygiene purposes or health control purposes, the amount may be below the above range.
  • nutraceutical composition according to the present invention in addition to diosmin, other ingredients that can give a synergistic effect to the main effect within the range that does not impair the main effect of the present invention, for example, vitamin C and It may contain such compounds for improving wrinkles or natural products, such as green tea extract, mulberry extract, licorice extract, lettuce extract, betel nut extract, golden extract, wild ginseng extract.
  • the dietary supplement composition formulated in the form as described above may be added to the food as it is or used with other foods or food ingredients, and may be appropriately used according to conventional methods.
  • foods include drinks, meats, sausages, breads, biscuits, rice cakes, chocolate, candy, snacks, confectionery, pizza, ramen, dairy products including other noodles, gums, ice creams, various soups, beverages, alcoholic beverages and vitamin complexes. , Dairy products and dairy products, and all functional foods in the conventional sense.
  • the health functional food composition of the present invention When the health functional food composition of the present invention is a drink, it contains diosmin as an essential ingredient in the ratio indicated, and there are no particular restrictions on other ingredients used for the purpose of preparing other drinks, and various flavoring agents such as ordinary drinks.
  • natural carbohydrate or the like as an additional component.
  • natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • a natural flavoring agent such as a natural flavoring agent, a synthetic flavoring agent, etc.
  • the proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
  • the nutraceutical composition of the present invention is a variety of nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like.
  • the food composition of the present invention may contain a pulp for producing natural fruit juice and fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the diosmin of the present invention.
  • the present invention also provides a pharmaceutical or quasi-drug composition having a skin moisturizing improvement, skin exfoliation, skin elasticity improvement, erythema suppression, wrinkle improvement and / or skin photoaging improvement effect containing diosmin or a salt thereof as an active ingredient. .
  • the diosmin of the present invention When using the diosmin of the present invention or a pharmaceutically acceptable salt thereof as a medicine, it may further contain one or more active ingredients exhibiting the same or similar functions.
  • it may include known skin wrinkle improving ingredients or elasticity enhancing ingredients.
  • additional skin wrinkle improving component and elasticity enhancing component By including additional skin wrinkle improving component and elasticity enhancing component, the wrinkle improvement and elasticity enhancing effect of the composition of the present invention can be further enhanced.
  • the pharmaceutical composition is a wrinkle improving component known in the art, any one or more selected from the group consisting of vitamin C, retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract It may further comprise a skin wrinkle improving ingredient.
  • the additional skin wrinkle improving component may be included in 0.0001 to 10% by weight relative to the total weight of the composition, the content range is based on requirements such as collagen synthesis promoting activity, skin safety, ease of formulation of the compound of Formula 1 Can be adjusted accordingly.
  • composition for improving skin wrinkles and elasticity of the present invention may further comprise a pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers may contain various components such as buffers, sterile water for injection, general saline or phosphate buffered saline, sucrose, histidine, salts, polysorbates and the like.
  • the pharmaceutical composition of the present invention may be administered orally or parenterally, and may be administered in the form of a general pharmaceutical preparation, for example, in various formulations, orally and parenterally, in the case of clinical administration.
  • Diluents or excipients such as extenders, binders, wetting agents, disintegrants, surfactants and the like.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in the pharmaceutical composition of the present invention, for example, starch, calcium carbonate, It may be prepared by mixing sucrose or lactose, gelatin and the like.
  • Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. .
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the pharmaceutical composition of the present invention may provide a desirable skin moisturizing improvement, skin exfoliation, skin elasticity improvement, erythema suppression, wrinkle improvement or skin photoaging improvement when including an effective amount of diosmin or a pharmaceutically acceptable salt thereof.
  • the term 'effective amount' means an amount of a compound capable of inhibiting or inhibiting generation of wrinkles on the skin or alleviating wrinkles already produced.
  • the effective amount of diosmin or a pharmaceutically acceptable salt thereof contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, the method by which the compound is applied to the skin and the time it stays on the skin.
  • composition when the composition is commercialized as a medicament for dermatological treatment due to wrinkle formation, elasticity reduction, and blemishes of the skin, diosmin or a pharmaceutical composition thereof is present at a higher concentration than when it is commercialized as a cosmetic product that is applied to the skin on a daily basis. It may include an acceptable salt.
  • the term "quasi drug” used in the present invention refers to articles that have a lesser action than drugs among those used for the purpose of diagnosing, treating, ameliorating, alleviating, treating or preventing diseases of humans or animals.
  • the drug is used for the purpose of medicine, and it includes a product used for the treatment or prevention of diseases of humans and animals, and a product having a slight or no direct action on the human body.
  • the quasi-drug composition of the present invention is used for the purpose of improving skin moisturizing, removing skin dead skin, enhancing skin elasticity, suppressing erythema, improving skin wrinkles and / or improving skin photoaging, and is not particularly limited in the formulation thereof.
  • It may be a cosmetic composition having a formulation of a flexible cosmetics, nourishing cosmetics, massage creams, nutrition creams, packs, mask packs, mask sheets, gels or skin adhesive cosmetics, and also lotions, ointments, gels, creams, patches or sprays.
  • It may be a transdermal dosage form such as
  • the quasi-drug composition may be optionally selected and blended with other ingredients according to the formulation or purpose of use of other quasi-drugs.
  • the mixed amount of the active ingredient can be suitably determined depending on the purpose of use (inhibition or relaxation).
  • it may include conventional adjuvants such as thickeners, stabilizers, solubilizers, vitamins, pigments and flavorings, carriers and the like.
  • the content of the diosmin or salt thereof of the present invention is preferably 0.0001 to 20% by weight, respectively, based on the total weight of the quasi-drug composition. If the content exceeds 20% by weight, the color and stability of the composition are inferior. If the content is less than 0.0001%, the effect is minimal.
  • Human dermal fibroblasts (normal, human, neonatal, ATCC No. PCS-201-010) were purchased from ATCC (Manassas, VA, USA). The purchased cells were cultured in a 37, 5% CO 2 incubator using a fibroblast growth medium (Promo Cell, Heidelberg) was used for the experiment.
  • a human fibroblasts In order to examine the collagen biosynthesis performance 12-well-was added to the plate (well-plate) 1.0 ⁇ 10 6 cells / by well Pipette DIOS min and vitamin C at a concentration of 100 ⁇ M respectively for 24 hours, CO 2 Cultured in the incubator. After removing the medium of each well, washed once with PBS, and again put 1 ml of PBS was irradiated with ultraviolet B (UVB) at 20 mJ / cm 2 conditions. PBS of each well was replaced with medium again and cultured for 24 hours, and then the amount of procollagen secreted into the medium was measured using a procollagen type C-peptide EIA kit (Takara Bio, Japan). The standard solution included in the collagen measurement kit was diluted by concentration, and the absorbance was measured at 450 nm to prepare a standard concentration curve and calculate the amount of collagen produced.
  • UVB ultraviolet B
  • Collagen the main protein constituting the skin, is synthesized in the form of procollagen from fibroblasts present in the dermis and then secreted into the extracellular matrix. Procollagen secreted into the extracellular matrix is decomposed by the procollagen peptidase on the cell surface and formed into active collagen. Therefore, the activated collagen content can be determined by measuring the C-peptide content.
  • FIG. 1 represents the means ⁇ SEM of three measurements from three independent wells. Mean values in other alphabets indicate statistical significance ( p ⁇ 0.05).
  • diosmin increases the amount of collagen activated in human skin fibroblasts, and this collagen increase effect is more effective when used with vitamin C.
  • mice The five-week-old female albino hairless mice (Skh-1) used in this example were purchased from Orient Bio (Gyeonggi-do, Korea) and subjected to a one-week adaptation period with solid feed. Experimental animals were divided into 4 groups and 5 animals were assigned to each group and used for the experiment. All experimental groups were divided into the normal control group (-UVB), the ultraviolet irradiation group (+ UVB), and the ingestion of diosmin (CV) or vitamin C (VitC) with ultraviolet irradiation. During the breeding period, feed and water were freely ingested, and the temperature was maintained at 22 ⁇ 1 and the humidity at 60 ⁇ 5%, and the photoperiod and dark cycle were adjusted to 12 hours daily.
  • -UVB normal control group
  • UVB the ultraviolet irradiation group
  • VitC vitamin C
  • the -UVB and + UVB groups consumed a refined diet prepared according to the AIN-93 rodent diet (Reeves, PG et al., J Nutr, 123: 1939-1951, 1993).
  • the composition of the detailed experimental diet is shown in Table 1 below. The diet was fed with water between 10 am and 11 am daily, and dietary intake was measured daily.
  • UVB ultraviolet B
  • the UV dose was 73 mJ / cm 2 for the first week, 146 mJ / cm 2 for the second week, and from 3 to 10 weeks. Irradiation at 219 mJ / cm 2 .
  • body weight and skin thickness were measured every week, and photographs of the back skin were taken. Skin thickness was measured in the hip region of hairless mice using a digital micro caliper (Marathon Watch Company Ltd, Ontario, Canada). The caliper used in the measurement was able to measure up to 0.01 mm, and it has a control function to apply a constant force to the thickness, so that the thickness of the skin was measured under the same force.
  • the skin of hairless mice subjected to UV irradiation for 10 weeks was made of silicone rubber to measure the extent of wrinkle formation. Attach a disk with a circular hole with a diameter of 1 cm to the back of the hairless mouse, mix the reagent for making a replica, thinly spread it on the back of the hairless mouse, dry it completely, and carefully remove the disk. was produced. Fabrication temperature of the replica plate was carried out in a constant temperature and humidity condition of 20 ⁇ 23, humidity of 45 ⁇ 50%, and a silicon rubber impression material (Epigem, Seoul, Korea) for producing a replica plate. Analysis of the simulated platen was performed using a computer image analyzer (Visioline VL650, CK electronic GmbH, Germany) for total wrinkle area, maximum wrinkle depth, mean depth and mean wrinkles. Four wrinkle indicator items such as mean length were analyzed.
  • the back skin tissue of hairless mice was extracted, fixed in 10% formalin, and then stained with Hematoxylin and eosin (H & E) and Masson's trichrome (M & T) by a Korean CFC (Gyeonggi-do, Korea), followed by an optical microscope (IX71, Olympus, JPN). ), And photographed using a digital camera (DP71, Olympus, JPN).
  • H & E Hematoxylin and eosin
  • M & T Masson's trichrome
  • Tissue was ground by adding 1 ml of Trizol solution per 0.1 g of back skin tissue, and centrifuged at 4, 12,000 xg for 10 minutes. The supernatant was transferred to a new tube and 200 ⁇ l of chloroform was added and vortexed. After repeating this process twice, the supernatant was transferred to a new tube and isoprophanol and supernatant were added at a 1: 1 ratio. After shaking vigorously 10 times and left at room temperature for 15 minutes, centrifugation was performed at 12,000 xg and 4 minutes for 10 minutes, the supernatant was removed, and 1 ml of 70% ethanol was added to the remaining precipitate, followed by 5 minutes at 7,500 xg and 4 minutes. Centrifugation was performed.
  • RNA pellet was dissolved using nuclease free water.
  • UV / VIS spectrophotometer Beckman coulter, DU730 was measured the concentration of RNA samples extracted at 260 nm and 280 nm wavelength, and the integrity of the RNA samples were confirmed by agarose gel electrophoresis.
  • CDNA was synthesized by reverse transcription using oligo dT primer and superscript reverse transcriptase (GIBCO BRL, Gaithersburg, MD, USA) on RNA samples extracted from the back skin tissue. PCR was performed using 5D and 3 'flanking sequences of the gene cDNA to be amplified as a template and cDNA obtained through reverse transcription, and the primer sequences used are shown in Table 2. 1 ⁇ l of the amplified PCR product was electrophoresed on 1% agarose gel to confirm DNA band.
  • the water content and elasticity enhancing effect of this diosmin was similar to the effect by vitamin C (Fig. 3).
  • the length was significantly reduced by 58%, and the antiwrinkle effect of diosmin was similar to the antiwrinkle effect observed in vitamin C (FIG. 5B).
  • the values in FIG. 5B are mean ⁇ SEM of 5 mice, and the alphabet above the bar represents a significant difference by one-way ANOVA followed by Duncan's multiple range test (p ⁇ 0.05). Therefore, it can be seen that ingestion of diosmin has an effect of significantly inhibiting wrinkle formation by ultraviolet irradiation.
  • the + UVB control group significantly increased the skin thickness compared to the normal group (-UVB) without UV irradiation. It was confirmed that the skin thickness was significantly reduced by 23% compared to the + UVB control (Fig. 6A).
  • the values in FIG. 6A are mean ⁇ SEM of 5 mice, with the alphabet above the bar representing a significant difference by one-way ANOVA followed by Duncan's multiple range test (p ⁇ 0.05).
  • the skin epidermal layer thickness of hairless mice by H & E staining of skin tissue was also observed that the + UVB control group thickened the skin epidermis layer compared to the normal group (-UVB) without UV irradiation. It was confirmed that the thickness of the epidermal layer thickened by was significantly reduced (FIG. 6B).
  • Collagen types 1 and 3 are proteins that constitute the cytoplasmic components of the dermal layer, and in particular, type 1 collagen is present in the largest amount of extracellular matrix proteins present in skin connective tissue.
  • MMPs that catalyze collagen degradation
  • MMP types known to increase by UV rays are known as Nos. 1, 3, and 9.
  • MMP-1 is known to cut the middle of collagen fibers
  • MMP-3 and MMP-9 are known to play a role in subdividing and cutting the cut collagen fibers (Quan T. et al. Elevated matrix metalloproteinases and collagen fragmentation).
  • collagen type 1 ⁇ 1 and ⁇ 2 and collagen type 3 ⁇ 1 of + UVB control group were compared with normal group (-UVB) without UV irradiation.
  • the expression of MMP-1a and -1b, MMP-3, and MMP-9 genes were significantly increased.
  • the expression of collagen type 1 ⁇ 1 and ⁇ 2 and collagen type 3 ⁇ 1 was significantly increased in the diosmin intake group compared to the + UVB control group, and the expression of MMP-1a and -1b, MMP-3, and MMP-9 genes was significantly increased. Decrease (Fig. 8). Therefore, it is thought that diosmin suppressed wrinkle formation by ultraviolet irradiation by increasing collagen protein synthesis of skin tissue and inhibiting collagen fiber degradation.
  • diosmin may have an effect to prevent or alleviate skin wrinkles caused by ultraviolet rays, which may be usefully used as functional cosmetics, health functional foods, medicines or quasi-drugs in the future.
  • components 1 to 8 are first dissolved by heating at a temperature of 70, and then components 9 to 13 are dissolved and dispersed in component 14 and emulsified to 70. Thereafter, the emulsified product was cooled to a temperature of 56, and then, component 15 dissolved in the fractionated component 9 was added, stirred, and cooled to room temperature to prepare.
  • the cosmetic composition containing the diosmin of the present invention or its cosmetically acceptable salt as an active ingredient has no skin side effects, improves wrinkles, increases the synthesis of collagen protein, and inhibits the degradation of collagen fibers. Excellent for wrinkle improvement
  • the skin moisture content was measured using a Koniometer in a constant temperature and humidity room at room temperature 25 and relative humidity 45% before application, and the Experimental Example 1 and Comparative Example 1 formulations of Table 3 were placed on the left and right sides of the face, respectively.
  • the skin was rested for 10 minutes after application and the skin moisture content was measured 12 hours after application and 24 hours after application.
  • the measuring device measured the moisture content of the skin using a moisture content meter (coneometer; CM820, Courage Khazaka electronic GmbH, Germany) that measures the moisturizing power by measuring the electric capacity of the skin according to the moisture content of the skin.
  • the conniometer measures the moisture level by measuring the amount of moisture by measuring the amount of water ions using a sensor and measuring the amount of moisture present in the skin epidermis, and the measuring method is as follows.
  • the sensor was wiped with a tissue such as Kimwipe and then measured again.
  • the measurement of the angular mass of the skin was measured by using Charm view (Moritex, Japan) in a constant temperature and humidity room at room temperature 25 and relative humidity of 45% before application, and Experimental Example 1 and Comparative Example 1 formulation of Table 3 above. Were applied to the left and right sides of the face, respectively, and the skin angular mass after 24 hours was measured, and the amount of skin exfoliation was calculated. Each value is shown in Table 6 below as an average value.
  • Example 2-1 Diosmin 1000 mg Vitamin mixtures Quantity Vitamin A Acetate 1.0 mg Vitamin E 0.13 mg Vitamin B1 0.15 mg Vitamin B2 0.5 mg Vitamin B6 0.2 ⁇ g Vitamin B12 10 mg Vitamin c 10 ⁇ g Biotin 1.7 mg Nicotinic acid amide 50 ⁇ g Folic acid 0.5 mg Calcium Pantothenate Quantity Mineral mixture Quantity Ferrous sulfate 1.75 mg Zinc oxide 0.82 mg Magnesium carbonate 25.3 mg Potassium phosphate monobasic 15 mg Dibasic Potassium Phosphate 55 mg Potassium citrate 90 mg Calcium carbonate 100 mg Magnesium chloride 24.8 mg
  • composition ratio of the vitamin and mineral mixture is a composition that is relatively suitable for the health functional food is mixed in a preferred embodiment
  • the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health functional food manufacturing method.
  • the granules may be prepared and used for preparing the nutraceutical composition according to a conventional method.
  • the solution prepared by stirring and heating at 85 for about 1 hour, filtered into 21 sterilized containers, sealed and sterilized and then refrigerated and stored Used to prepare beverage compositions.
  • the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
  • the ring was prepared so as to be 4 g per ring according to a conventional ring production method.

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Abstract

La présente invention concerne une composition cosmétique, une composition d'aliment fonctionnel de santé, et des compositions de médicament et de quasi-médicament, contenant de la diosmine ou son sel comme ingrédient actif et présentant des effets de réduction des rides de la peau, d'amélioration de l'hydratation de la peau, d'exfoliation de la peau, de renforcement de l'élasticité de la peau, de réduction des rides de la peau, d'inhibition de l'érythème, et de retardement du photovieillissement de la peau. La diosmine ou son sel selon la présente invention font preuve d'activités d'amélioration du niveau d'humidité de la peau, de réduction de la perte d'humidité de la peau, d'augmentation de la sécrétion de procollagène, de promotion de la biosynthèse, d'inhibition de la détérioration des fibres de collagène, d'inhibition de la décomposition des fibres de collagène, d'inhibition de l'érythème, et d'inhibition de l'hypertrophie épidermique, et ainsi peut être appliqué(e) de manière utile comme matériau destiné à un produit cosmétique fonctionnel, un aliment fonctionnel de santé, un médicament, un quasi-médicament, ou similaires pour fournir des effets d'amélioration de l'hydratation de la peau, d'exfoliation de la peau, de renforcement de l'élasticité de la peau, de réduction des rides de la peau, d'inhibition de l'érythème, de réduction des rides de la peau, et/ou de retardement du photovieillissement de la peau.
PCT/KR2017/004231 2016-06-09 2017-04-20 Composition contenant de la diosmine ou son sel comme ingrédient actif et présentant un effet d'amélioration de l'hydratation de la peau, d'exfoliation de la peau, de renforcement de l'élasticité de la peau, d'inhibition de l'érythème, de réduction des rides de la peau, ou de retardement du photovieillissement de la peau WO2017213346A1 (fr)

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