KR20170138754A

KR20170138754A - Composition having effects of skin moisturizing, exfoliating, improving skin elasticity, inhibiting erythema, anti-wrinkle or improving skin photoaging comprising cadaverin or salt thereof

Info

Publication number: KR20170138754A
Application number: KR1020160070960A
Authority: KR
Inventors: 박태선
Original assignee: 연세대학교 산학협력단
Priority date: 2016-06-08
Filing date: 2016-06-08
Publication date: 2017-12-18

Abstract

The present invention relates to a cosmetic composition, a health functional food composition, a cosmetic composition, a cosmetic composition, a cosmetic composition, a cosmetic composition, a cosmetic composition, a cosmetic composition, The present invention relates to cadaverine or a salt thereof. The cadaverine or a salt thereof according to the present invention is useful as an agent for improving skin moisture content, reducing skin moisture content, increasing procollagen secretion, promoting collagen biosynthesis, inhibiting collagen fiber damage, inhibiting collagen fiber degradation, It can be used as a material for functional cosmetics, health functional foods, medicines or quasi-drugs that provide skin moisturization, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / Can be usefully used.

Description

TECHNICAL FIELD The present invention relates to a composition having an effect of improving skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement or skin photo-aging improvement, which comprises cadaverine or a salt thereof as an active ingredient. , inhibiting erythema, anti-wrinkle or improving skin photoaging < RTI ID = 0.0 >

More particularly, the present invention relates to a composition containing cadarin or a salt thereof as an active ingredient, and more particularly to a composition containing cadaverine or a salt thereof as an active ingredient. More specifically, the present invention relates to a composition containing cadaverine or a salt thereof as an active ingredient, A cosmetic composition having an effect of improving skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement using cadaverine or a salt thereof suppressing eruption, erythema suppression, , A health functional food composition, a medicine and a quasi-drug composition.

Recent advances in medical technology have led to increased interest in skin care and health as life expectancy has been extended and quality of life has been improved and the desire for a healthy and beautiful life has increased. Various cosmetic functional cosmetics have been developed for the purpose of maintaining a healthy skin, and researches for prevention of skin wrinkle formation, mitigation and improvement have been actively carried out. In addition, recently, cosmetic ingredients reach skin dermis and there is a limitation in supplying nutrients. As a result of the change in perception that ingestion of nutrients or functional ingredients to the skin can provide a skin cosmetic enhancement effect, JNutr, 132, 3090-3097 (2002), Tanno, O. et al., &Lt; RTI ID = 0.0 > al., &Lt; / RTI & , Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier (Br J Derm, 143, 524-531, 2000).

The skin consists largely of epidermis, dermis and hypodermis. The outer layer of the epidermis, especially the outer layer of the epidermis, plays a role as a skin barrier, thereby causing loss of water and electrolytes from the skin While the dermis, through the synthesis of collagen and elastin, maintains the elasticity of the skin and supports the structure. In other words, collagen and elastin are the main proteins produced in fibroblasts, which are involved in the mechanical durability of the skin, the binding force and the resilience of tissues (Moskowit, RW et al, Role of collagen hydrolysate in bone and joint disease, Semin Arthritis Rheu, 87, 2000). Collagen constitutes various isoforms according to its morphological and structural characteristics. There are 28 types of collagen isotypes in human tissues. Collagen existing in skin tissues is classified into types 1 and 3. 4. 6. 7. 13, 14, 17, etc. are known. Collagen type 1 and 3 form the intercellular component of the dermis, while collagen type 7 is the main component of the dermal and epidermal junction (Pei, M. et al., Expression of collagen type I, II and III in the loose body of osteoarthritis, J. Orthop. Sci., 5: 288, 2000).

In skin connective tissue, type I collagen is the most abundant of extracellular matrix proteins, and other proteins such as elastin, fibronectin, integrin, fibrillin, and proteoglycan exist. The newly synthesized procollagen is secreted into the extracellular space of the skin cells through an enzymatic reaction and forms a microfibril of a triple helix configuration, while microfibrils form leucine-rich small proteoglycans -rich small proteoglycans) to form a fibril. As a result, these fibrils are gathered to form collagen fibers that provide skin's binding force and elasticity (Bateman, J. F. et al., Collagen superfamily. Extracellular matrix, Harwood, New York, 2, 22-26, 1996).

Skin aging is known to be caused by a decrease in collagen content, which is the protein that occupies most of the collagen in skin dermal tissue. Since collagen gives skin tension and strength, collagen reduction has a very deep relationship with skin aging and wrinkle formation have. Skin aging is largely divided into endogenous aging by physiological aging and photoaging caused by continuous exposure to ultraviolet radiation (UV). Repeated exposure to ultraviolet light results in increased collagenase and denaturation and destruction of collagen fibers, reducing skin elasticity and promoting the production of wrinkles. In other words, the development of reactive oxygen species (ROS) is increased in skin tissue exposed to ultraviolet rays continuously, and the latter is a signal transduction system mediated by growth factor receptor (EGF-R), tumor necrosis factor (TNF) (Sachsenmaier, C. et al., Involvement of growth factor receptors in the mammalian UVC response. Cell, 78: 963-972, 1994; Dy, LC et al., Augmentation of ultraviolet B radiation-induced tumor necrosis factor production by the epidermal platelet-activating factor receptor. J. Biol. Chem .: 274, 26917-2692, 1999). Activation of these receptors results in continuous phosphorylation, which activates proteins that mediate downstream signaling, including mitogen-activated protein kinase (MAPK), resulting in activator protein-1 (AP-1 ) And nuclear factor κB (NF-κB) to induce inflammatory responses and promote the activity of collagenases such as matrix metalloproteinases (MMPs), thereby reducing skin elasticity and promoting wrinkle formation (Kang, S. et al., Inflammation and extracellular matrix degradation mediated by activated transcription factor nuclear factor-kB and activator protein-1 in Inflammatory acne lesions in vivo. Am J. Pathol., 166: 1691-1699, 2005) . AP-1 regulates the expression of a number of genes involved in cell growth and differentiation and strongly regulates the expression of some MMPs. Among MMPs whose expression is regulated by AP-1, MMP-1 is known as collagenase 1, and type 1 and 3 collagen are substrates.

The inventors of the present invention have conducted research to develop a food or cosmetic material having an effect of reducing wrinkles by inhibiting collagenase activity and promoting the synthesis of collagen in natural products with low side effects. As a result, cadaverin has been shown to improve skin wrinkles , Skin moisturization improvement, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement, and / or skin photoaging improvement.

Previously, it has been reported that cadaverine has the effect of reducing blood pressure in rats (Til et al., Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats. Food and Chemical Toxicology 35: 337-348 , 1997), there was no report showing physiological activity in relation to skin health.

It is an object of the present invention 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 improvement.

Another object of the present invention is to provide a health functional food composition having skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement.

Another object of the present invention is to provide a pharmaceutical or quasi-drug composition having skin moisturizing effect, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement effect.

In order to solve the above-mentioned problems, the present invention provides a cosmetic composition comprising cadarin or a cosmetically acceptable salt thereof as an active ingredient for improving skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / A cosmetic composition having an improving effect is provided.

The present invention also relates to a medicament for improving the skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement containing cadaverine or a pharmaceutically acceptable salt thereof as an active ingredient To provide a food composition.

According to a preferred embodiment of the present invention, the cadaverine or a cosmetically acceptable salt thereof may be contained in an amount of 0.0001 to 20% by weight based on the total weight of the cosmetic composition.

According to another preferred embodiment of the present invention, the cosmetic composition may be at least one selected from the group consisting of a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, A formulation selected from the group consisting of a pack, a mask pack, a mask sheet, an exfoliant, a soap, a shampoo, a cleansing foam, a cleansing lotion, a cleansing cream, a body lotion, a body cleanser, a latex, a press powder, a loose powder, &Lt; / RTI >

According to another preferred embodiment of the present invention, the health functional food composition may be prepared in any one form selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings.

According to another preferred embodiment of the present invention, the cosmetic composition or health functional food composition may further comprise a skin wrinkle improving component.

According to another preferred embodiment of the present invention, the further skin wrinkle improving component is selected from the group consisting of vitamin C, retinoic acid, transforming growth factor (TGF), animal placenta-derived protein, betulinic acid and chlorella extract Lt; / RTI >

The present invention also provides a pharmaceutical or quasi-drug composition having skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement, and / or skin photoaging improvement effect containing cadaverine or a salt thereof as an active ingredient .

The composition containing the cadaverine or a salt thereof as an active ingredient of the present invention can be used as an effective ingredient for improving skin moisture content, decreasing skin moisture evaporation amount, increasing amount of procollagen secretion, promoting collagen biosynthesis, inhibiting collagen fiber damage, inhibiting collagen fiber decomposition, Can be effectively used for improving wrinkles of skin, improvement of skin moisturization, removal of skin exfoliation, improvement of skin elasticity, suppression of erythema, improvement of skin wrinkles and / or improvement of skin photoaging. In addition, since cadaverine of the present invention is a natural product, it is safe for the human body and has few side effects, so that it can be used variously as a material such as a cosmetic, a health functional food, a medicine or a quasi-drug.

FIG. 1 is a graph showing the results of measuring the amount of procollagen secreted by UVB at 20 mJ / cm 2 in human skin fibroblasts, followed by treatment with 100 μM of vitamin C or cadaverine for 24 hours and ELISA analysis (-UVB: Vitamin B: Vitamin C, UVB, Vitamin B, Vitamin B, Vitamin B, Vitamin C, Vitamin B, Vitamin C, Vitamin C, An experimental group treated with fucadarin and vitamin C).
Fig. 2 is a graph showing weight gain and dietary intake of mice fed the experimental diet having the composition of Table 1 (A: body weight, B: weight gain, C and D: dietary intake).
FIG. 3 is a graph showing the moisture content (A), water evaporation amount (B), elasticity (C) and erythema index (D) of the skin tissue of a mouse ingested with an experimental diet having the composition shown in Table 1.
4 is a photograph showing the dorsal skin tissue of each of the mice ingested with the experimental diet having the composition shown in Table 1;
Fig. 5 is a photograph (A) and a graph (B) showing the degree of wrinkle formation of the dorsal skin tissue of the mice ingested with the experimental diet having the composition shown in Table 1. Fig.
FIG. 6 is a graph (A) of the skin thickness of a mouse ingested with an experimental diet having the composition shown in Table 1 and a skin skin layer photograph.
FIG. 7 is a photograph showing changes in the amount and morphology of collagen fibers in a mouse in which an experimental diet having the composition shown in Table 1 was ingested.
FIG. 8 shows the results of RT-PCR measurement of changes in expression of collagen and MMP genes in tissues such as reptiles treated with cadaverine.

Hereinafter, the present invention will be described in more detail.

As described above, cadaverine has been known to have an effect of decreasing blood pressure. However, it has been known that cadaverine has a physiological activity related to skin health, namely, improvement of skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, There has been no report on the effect of improving skin photoaging.

The present inventors confirmed a novel activity of cadaverine in relation to skin health and developed a cosmetic composition and a health functional food composition containing cadaverine or a salt thereof as an active ingredient.

The composition provided by the present invention is excellent in skin moisture content, reduced skin moisture evaporation, increased amounts of procollagen secretion, promotion of collagen biosynthesis, inhibition of collagen fiber damage, inhibition of collagen fiber decomposition, erythema suppression, Improvement of skin moisturization, removal of skin exfoliation, improvement of skin elasticity, suppression of erythema, improvement of skin wrinkles, and / or improvement of skin photoaging.

Accordingly, the present invention relates to a cosmetic composition having an effect of improving skin moisturization, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / or skin photoaging improvement containing cadaverine or a cosmetically acceptable salt thereof as an active ingredient .

Cadabelin is a ptomaine-based compound represented by the following formula (1): Cas No. 462-94-2, NH ₂ (CH ₂ ) ₅ NH ₂ , and a molecular weight of 102.18 g / mol. Cadaverine is also called tinnitus, such as 1,5-pentanediamine, pentamethylenediamine. Cadabelin is a pale yellow liquid component with a melting point of 11.83 and a boiling point of 179.1.

[Chemical Formula 1]

The generic name of nitrogen compounds produced by chemical action such as decarbonation action of an amino acid and amino group transfer action is called biogenic amines, and therefore, bioenic amines are a protein-containing food And may be caused by microorganisms or biochemical activity. Cadabelin is a representative biogenic amine produced by the decarboxylation of lysine and is widely distributed as a normal component of the body even though it has a place where the decay of meat and other proteins proceeds.

The physiological activity of cadaverine reported to date has been reported to reduce blood pressure in rats (Til et al., Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats. Food and Chemical Toxicology 35: 337-348,1997). Rats were reported to have acute oral toxicity at doses above 2,000 mg / kg body weight when orally administered with cadaverine, and the no-observed-adverse-effect level (NOAEL) value of cadaverine was 180 mg / kg body weight / day. (Til et al., Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats, Food and Chemical Toxicology 35: 337-348, 1997).

Therefore, administration of cadarin at a dose of 180 mg / kg to 2,000 mg / kg, preferably 180 mg / kg to 1,000 mg / kg, is very toxic or does not exist and thus can be used as a cosmetic composition, .

The method for obtaining the cadaverine of the present invention is not particularly limited, and may be separated from natural products, chemically synthesized using a known production method, or commercially available.

In the present invention, the cadaverine may include cadaverine hydrate, cadaverine derivative, and the like, and may include a solvent or a stereoisomer thereof within the range of the same effect.

In the present invention, the term " improvement of skin wrinkles " means maintaining or strengthening the ability to relate to the wrinkles and elasticity of the skin. Collagen (collagen) and elastin (elastin), which are the collagen fibers of the skin dermis layer, play a key role in maintaining skin elasticity. Collagen biosynthesis is affected by internal and external skin. Specifically, the skin cells are reduced in cellular activity due to natural aging, and collagen fibers are decreased. When extreme ultraviolet rays are irradiated as an external factor, or when active oxygen generated by stress or the like causes thiol (-SH) To increase the expression of collagen and elastase, thereby increasing the wrinkles of the skin and reducing the elasticity, thereby aging the skin.

In the context of the present invention, the term "cosmetically acceptable salt", "pharmaceutically acceptable salt", "pharmaceutically acceptable salt" or "salt thereof" refers to an acid addition salt formed by a free acid have. Acid addition salts can be prepared in a conventional manner, for example, by dissolving the compound in an excess amount of an aqueous acid solution and precipitating the salt with a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. It is also possible to heat an equimolar amount of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water, and then evaporate the mixture to dryness, or the precipitated salt may be subjected to suction filtration.

As the free acid, an inorganic acid or an organic acid can be used. The inorganic acid may be, for example, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. These may be used alone or in admixture of two or more. Non-limiting examples of the organic acid include methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, The present invention also relates to the use of a compound of formula (I) as an acid, citric acid, lactic acid, glycollic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillyric acid, hydroiodic acid and the like. These may be used alone or in combination of two or more.

In addition, the cadaverine can be made into a cosmetically or pharmaceutically acceptable metal salt using a base. The alkali metal or alkaline earth metal salt can be obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the non-soluble compound salt, and evaporating and drying the filtrate. The metal salt is preferably, but not limited to, sodium, potassium or calcium salt. The corresponding silver salt can also be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

The salts of cadaverine may include all salts of acidic or basic groups that may be present in the compound of cadaverine, unless otherwise indicated. For example, the salt of cadaverine may include sodium, calcium and potassium salts of a hydroxyl group, and other cosmetically acceptable salts of amino groups include hardro-bromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate (Salicylate) salts such as hydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p- toluenesulfonate Can be produced through a production method.

The effective amount of cadaverine or a cosmetically acceptable salt thereof in the cosmetic composition of the present invention is not particularly limited and may be from 0.0001 to 20% by weight based on the total weight of the composition. Less than 0.0001% by weight of cadaverine or a salt thereof in the cosmetic composition may not have a wrinkle-reducing effect due to its small amount, and more than 20% by weight of cadaverine or its salt may exhibit the previously known toxicity.

In one embodiment of the present invention, when cadaverine was administered to human skin fibroblasts irradiated with ultraviolet light, the amount of procollagen type I C-peptide (PIP) secretion was increased as compared with control cells irradiated only with ultraviolet light (FIG.

In another embodiment of the present invention, the experimental diet shown in Table 1 containing cadaverine together with ultraviolet irradiation was supplied to reared mice for 10 weeks, and skin moisture content, moisture evaporation amount, elasticity, erythema index, MMP-1a, MMP-1b, MMP-3, and MMP-9 gene expression were measured in the presence of collagen type 1α1, 1α2, and 3α1. As a result, it was confirmed that cadaverine significantly increased skin moisture content and elasticity, and significantly decreased water evaporation and erythema index (Fig. 3). In addition, cadaverine has the effect of improving the wrinkles of the skin of the back of the experimental animals (Fig. 4), significantly reducing the wrinkle area, depth and length of the skin to significantly inhibit wrinkle formation (Fig. 5) (Fig. 6), the density of collagen fibers is dense and the arrangement is maintained regularly (Fig. 7), and the expression of collagen types 1 alpha 1, 1 alpha 2 and 3 alpha 1 is significantly , And significantly decreased the expression of MMP-1a, MMP-1b, MMP-3, and MMP-9 genes, thereby increasing the synthesis of collagen proteins and inhibiting the degradation of collagen fibers, effectively suppressing the formation of wrinkles by ultraviolet irradiation (Fig. 8).

Therefore, the composition comprising cadaverine or a salt thereof of the present invention is useful as a functional cosmetic for providing skin wrinkle improvement, skin moisturization improvement, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement and / Health functional foods, medicines or quasi-drugs.

The term "cosmetic composition" used in the present invention is a composition containing the above-mentioned compound, and the formulation can be in any form. Examples of such formulations include cosmetic preparations made using the above composition, such as creams such as nutritional creams, eye creams, massage creams, cleansing creams, lotions such as packs, nutritional lotions, essences, softening longevity, A powder, a foundation, a makeup base, and the like, and may be manufactured and commercialized in any form of these formulations in order to achieve the object of the present invention, and the present invention is not limited thereto. Further, the cosmetic composition according to the present invention can be formulated into a usual cosmetic preparation method.

Specifically, the cosmetic composition of the present invention can be used as a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisturizing cream, a hand cream, And may be any one selected from the group consisting of soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, milky lotion, press powder, loose powder and eye shadow.

The cosmetic composition of the present invention may contain, in addition to cadavirin or a salt thereof, an excipient, carrier, and other additives, and it is possible to apply a common ingredient to be blended with a general skin cosmetic composition as needed.

Specifically, the cosmetic composition of the present invention may further comprise a transdermal penetration enhancer. As used herein, the term transdermal penetration enhancer is a composition that allows a desired component to penetrate into vascular cells of the skin at a high absorption rate. But are not limited to, other phospholipid components, liposomal components, and the like, preferably used in lecithin cosmetics.

As the oil which can be mainly used as an oil component, at least one selected from vegetable oil, mineral oil, silicone oil and synthetic oil can be used. More specifically, there may be mentioned mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitisviniferase seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, Chicone, cyclopentasiloxane, sunflower seed oil and the like can be used.

Further, 0.1 to 5% by weight of a surfactant, a higher alcohol and the like may be added to reinforce the emulsifying ability. As such surfactants, conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, phospholipids and the like can be used. Specific examples thereof include sorbitan sesquiunorate, polysorbate 60 Sorbitan stearate, sorbitan stearate, sucrose stearate / sucrose cocoate, glyceryl stearate / polyethylene glycol-100 Stearate, cetearyl-6 olivate, arachidyl alcohol / behenyl alcohol / arachidyl glucoside, polypropylene glycol-26-butes-26 / polyethylene glycol-40 hydrogenated castor oil, have. As the higher alcohol, an alcohol having 12 to 20 carbon atoms such as cetyl alcohol, stearyl alcohol, octyldodecanol, isostearyl alcohol, etc. may be used alone or in admixture of one or more.

In order to control the viscosity or hardness of the water phase, 0.001 to 5% by weight of at least one thickening agent such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate and the like may be further added.

In addition, the cosmetic composition of the present invention may contain, if necessary, a medicinal ingredient such as higher fatty acids and vitamins, an ultraviolet screening agent, an antioxidant (butylhydroxyanisole, gallic acid propylate, eicosorbic acid, tocopheryl acetatide, (Triethanolamine, citric acid, citric acid, sodium citrate, malic acid, citric acid, etc.), preservatives (methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinyl urea, chlorphenesin and the like) And the like), a humectant (glycerin, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin, etc.), sodium hydrogen carbonate , Betaine, glycereth-26, methylglucose-20, etc.), lubricant, and the like.

In addition, the cosmetic composition of the present invention further comprises a substance capable of supplementally providing an essential nutrient to the skin, and preferably it may contain an auxiliary agent including, but not limited to, a natural flavor, a cosmetic flavor, have.

In addition, the cosmetic composition of the present invention may further comprise a skin wrinkle improving component or a skin elasticity improving component. The specific skin wrinkle improving component or skin elasticity enhancing component may be one or more selected from the group consisting of vitamin C, retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract, and most preferably, Vitamin C < / RTI >

In one embodiment of the present invention, when cadaverine with vitamin C was treated with human skin fibroblasts irradiated with ultraviolet rays, the amount of collagen was measured at a higher level than that of cadaverine or vitamin C alone, (Fig. 1).

The above description of " cadaverine " and " its pharmaceutically acceptable salt " is as described above.

The term " health functional food " in the present invention refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and rings using raw materials and components having useful functions in the human body. Here, 'functional' refers to the structure and function of the human body to obtain nutritional effects and obtain useful effects for health use such as physiological action. The health functional food of the present invention can be prepared by a method commonly used in the art and can be prepared by adding raw materials and ingredients that are conventionally added in the art. In addition, the formulations of the above health functional foods may also be manufactured without limitations as long as they are acceptable as health functional foods. The health functional food composition of the present invention is advantageous in that it has no side effects that may occur when a medicine is taken for a long time by using a food as a raw material, unlike a general medicine, and is excellent in portability and improves skin moisturization, skin exfoliation, , Erythema suppression, skin wrinkle improvement and / or skin photoaging improvement.

The health functional food composition of the present invention may be prepared in any one form selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings.

The health functional food composition according to the present invention may be formulated in the form of a powder, a liquid, a tablet, a soft capsule, a granule, a tea bag, an instant tea or a drink by incorporating cadarin as an active ingredient. The content of cadaverine as an active ingredient can be appropriately determined depending on the intended use (for prevention or improvement). Generally, the amount of cadaverine contained in the health functional food composition may be 0.1 to 90% by weight of the total food weight. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range. In addition, the health functional food composition according to the present invention may contain other ingredients that can give synergy to the main effect, such as vitamin C and vitamin C, in addition to cadaverine, to the extent that the main effect of the present invention is not impaired Such as wrinkle-improving compound or green tea extract, mulberry extract, licorice extract, mulberry bark extract, bingo extract, golden extract, and wild ginseng extract.

The health functional food composition formulated in the above-described form can be added directly to the food or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. Examples of food products include dairy products including drinks, meat, sausage, bread, biscuits, rice cakes, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, soups, , Dairy products and dairy products, and all health functional foods in the ordinary sense are included.

When the health functional food composition of the present invention is a drink, it contains cadaverine as an essential ingredient in the indicated ratio, and there are no particular restrictions on other ingredients used for the purpose of producing other drink products, and various flavors Or natural carbohydrate as an additional ingredient. Examples of such natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors and synthetic flavors and the like can be used as the flavors other than those described above. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition, the health functional food composition of the present invention can be used as a nutritional supplement, a vitamin, a mineral (electrolyte), a flavor such as a synthetic flavor and a natural flavor, a coloring agent and a thickening agent (cheese, chocolate etc.), a pectic acid and its salt, And salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the inventive food composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may 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 cadaverine of the present invention.

The descriptions of the above " cadaverine " and " salt thereof " are as described above.

When the cadaverine of the present invention or a pharmaceutically acceptable salt thereof is used as a medicine, it may further contain one or more active ingredients exhibiting the same or similar functions. For example, a known skin wrinkle-improving component or elasticity-enhancing component may be included. The addition of the additional skin wrinkle improving ingredient and the elasticity enhancing ingredient can further improve the wrinkle improving and elasticity improving effect of the composition of the present invention. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the present invention, the pharmaceutical composition is a wrinkle-improving ingredient known in the art, and includes at least one selected from the group consisting of vitamin C, retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract And may further comprise a skin wrinkle improving ingredient. The additional skin wrinkle improving ingredient may be contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the above content range may be determined according to requirements such as collagen synthesis promoting activity, skin safety, Can be adjusted accordingly.

In addition, the pharmaceutical composition for improving skin wrinkles and improving elasticity of the present invention may further comprise a pharmaceutically acceptable carrier.

Pharmaceutically acceptable carriers may contain a variety of ingredients such as buffer, injectable sterile water, normal saline or phosphate buffered saline, sucrose, histidine, salts and polysorbates.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, various forms of oral and parenteral administration at the time of clinical administration. In the case of formulation, , An extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like.

In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The pharmaceutical composition of the present invention can provide desirable skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement or skin photo-aging improvement effects when it contains an effective amount of cadaverine or a pharmaceutically acceptable salt thereof have. In the present invention, the term "effective amount" refers to the amount of a compound capable of inhibiting or inhibiting the generation of wrinkles of the skin or alleviating the wrinkles already formed. The effective amount of cadaverine or a pharmaceutically acceptable salt thereof contained in the composition of the present invention will depend on the form in which the composition is produced, the manner in which the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a medicament for dermatological treatment due to wrinkle formation, reduced elasticity, or stain on the skin, it is preferred that the composition has a higher concentration of cadaverine or its pharmaceutical Lt; / RTI > acceptable salts.

The term "quasi-drug product" used in the present invention means products that are less active than drugs, among the products used for diagnosing, treating, improving, alleviating, treating or preventing diseases of human or animal. For example, Quasi-drugs are products that are used for the purpose of treating or preventing diseases of humans or animals, products that are mild or have no direct action on the human body.

The quasi-drug composition of the present invention is used for the purpose of improving skin moisturization, removing horny skin, enhancing skin elasticity, suppressing erythema, improving skin wrinkles and / or improving skin photoaging, and there is no particular limitation in its formulation, A lotion, an ointment, a gel, a cream, a patch or a spray, or a cosmetic composition having the form of a softening agent, a softening agent, a nutrient lotion, a massage cream, a nutritional cream, a pack, a mask pack, a mask sheet, &Lt; / RTI >

In addition, the quasi-drug composition in each formulation can be blended by arbitrarily selecting other components according to the formulation of the other quasi-drugs, the purpose of use, and the like. The mixing amount of the active ingredient can be appropriately determined according to the intended use (inhibition or relaxation). For example, conventional adjuvants such as thickeners, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers and the like.

The content of cadaverine or its salt of the present invention is preferably 0.0001 to 20% by weight based on the total weight of the quasi-drug composition. When it is more than 20% by weight, the color and stability are poor when the composition is prepared, and when it is less than 0.0001%, the effect is insignificant.

In addition, in the quasi-drug composition of each formulation, components other than the above-mentioned essential components may be mixed and selected without difficulty by those skilled in the art depending on the formulation or purpose of use.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Wrinkle-reducing efficacy of cadaverine using human skin fibroblast

1-1. Experimental Method

1) Cell culture

Human dermal fibroblast (normal, human, neonatal, ATCC No. PCS-201-010) was purchased from ATCC (Manassas, VA, USA). The cells were cultured in 37, 5% CO2 incubator using fibroblast growth medium (Promo Cell, Heidelberg).

2) Procollagen Type I C-peptide (PIP) concentration measurement

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 cadaverine and vitamin C at a concentration of 100 μM respectively for 24 hours, CO ₂ Lt; / RTI > After removing the media from each well, the plate was washed once with PBS, and 1 ml of PBS was added thereto. Ultraviolet B (UVB) was then irradiated at 20 mJ / cm ² . PBS was re-cultured for 24 hours, and the amount of procollagen secreted into the medium was measured using procollagen type C-peptide EIA kit (Takara Bio, Japan). The standard solution contained in the collagen measurement kit was diluted by concentration, absorbance was measured at 450 nm to prepare a standard concentration curve and the amount of collagen production was calculated.

1-2. Experiment result

1) Changes in the amount of procollagen secreted

Collagen, the main protein that makes up the skin, is synthesized in the form of procollagen in fibroblasts in the skin dermis and then secreted into the extracellular matrix. Procollagen secreted into the extracellular matrix is broken down by the procollagen peptidase present on the cell surface and is formed into active collagen. Therefore, the active collagen content can be measured by measuring the C-peptide content. Each value in Figure 1 represents means SEM of three measurements from three independent wells. The mean value of the other alphabets is statistically significant ( p <0.05). The amount of procollagen type I C-peptide (PIP) secreted into the extracellular matrix of the human skin fibroblasts by treatment with ultraviolet light was measured in the control cells (+ UVB) irradiated with ultraviolet light. (UVB), and the amount of collagen was significantly increased in UV-irradiated cells (CV) treated with cadaverine compared to UV-irradiated control cells (+ UVB). On the other hand, the amount of collagen in the cells treated with vitamin C (VitC + CV) was significantly increased by 53% compared with that of UV-irradiated control cells (+ UVB), indicating that vitamin C (+ 37%) or cadaverine 8%) than the amount of collagen observed in cells treated alone (Figure 1). These results, when applied to call informality, show synergistic effects when treating cadaverine and vitamin C together. Thus, cadaverine increases the amount of activated collagen in human dermal fibroblasts, and this effect of collagen increase is more effective when used with vitamin C.

Evaluation of efficacy of moisturizing and elasticity enhancement of wrinkle of skin of cadaverine using mouse

2-1. Experimental Method

1) Experimental formula is prepared, raising of experimental animals and ultraviolet irradiation

The 5-week-old female albino hairless mouse (Skh-1) used in this example was purchased from Gyeonggi-do, Korea and subjected to a week of adaptation period with a solid feed. The experimental animals were divided into 4 groups and 5 mice were assigned to each group. All experimental groups were divided into two groups: normal controls (-UVB), UV-irradiated group (UVB), cadaverine (CV) or vitamin C (VitC). During the breeding period, feed and water were freely consumed. The temperature was maintained at 22 ± 1, the humidity was maintained at 60 ± 5%, and the light period and the dark cycle were adjusted to 12 hours each day.

-UVB group and + UVB group were fed a purified diet prepared according to the AIN-93 rodent diet composition (Reeves, PG et al., J Nutr, 123: 1939-1951, 1993) The diets were supplemented with 0.2% cadaverine (Sigma-Aldrich), and the VitC group was supplemented with 0.2% vitamin C (Sigma-Aldrich) in AIN-93 purified diet for 10 weeks. The composition of the experimental diet is shown in Table 1 below. Diets were supplied daily with water between 10 am and 11 am, and the dietary intake was measured daily.

Experimentation table ingredient AIN- 93G diet
(g / kg diet) Cadaveline Supplement Diet (CV)
(g / kg diet) Vitamin C supplement (VitC)
(g / kg diet) Casein 200 200 200 Maltodextrin 132 132 132 Corn starch 397.486 395.486 395.486 Sucrose 100 100 100 cellulose 50 50 50 Soybean oil 70 70 70 Vitamin complex 10 10 10 Mineral complex 35 35 35 Colin Beavertre 2.5 2.5 2.5 L-cystine 3 3 3 Tert-butyhydroquinone 0.014 0.014 0.014 Cadaverine - 2 - Vitamin C - - 2 Total (g) 1,000 1,000 1,000

During the experimental period, ultraviolet B (UVB) was irradiated three times a week on the back of the hairless mice. The amount of ultraviolet irradiation was 73 mJ / cm ² for the first week, 146 mJ / cm ^{2 for the second} week, 219 mJ / cm < ^{2 &} gt ;. Body weight and skin thickness were measured weekly during the breeding, and photographs of the back skin were taken. The skin thickness was measured in the buttocks of reared mice using a digital micro caliper (Marathon Watch Company Ltd., Ontario, Canada). The calipers used in the measurement were able to measure up to 0.01 mm and had a control function to apply constant force to the thickness, and it was possible to measure the skin thickness under the same force.

On the last day of the experiment, the animals were sacrificed for 6 hours and anesthetized, blood and skin tissue were collected. Blood samples were collected from the abdominal subclavian vein using a syringe and placed in EDTA-coated tubes. After centrifugation at 2,000 × g for 15 minutes, the plasma was separated and stored frozen at -70 ° C. until analysis. Some of the skin tissues were immediately stored in -70 freezer and used for molecular biology, and some were fixed in 10% formalin solution for immunohistochemical staining.

2) Skin moisturizing, elasticity and erythema index measurement

The skin moisture content, water evaporation, elasticity and erythema index of the experimental animals were measured once at the end of the experiment using Corneometer®, Tewameter®, Cutometer®, and Mexameter® (CK Electronics GmbH), respectively. In the measurement, the numerical value obtained by lightly pressing a certain portion of the test animal or the like was recorded.

3) Wrinkle measurement of skin tissue

The skin of hairless mice exposed to ultraviolet rays for 10 weeks was simulated with silicone rubber to measure the degree of formation of wrinkles. A disk with a circular hole with a diameter of 1 cm was attached to the back part of the hairless mouse, and the reagent for preparing the simulated plate was mixed and thinly spread on the back part of the hairless mouse, completely dried, and then carefully peeled off the disk, Respectively. The preparation temperature of the simulated plate was 20 ~ 23, the humidity was 45 ~ 50%, and the impression material (Epigem, Seoul, Korea) was used. Using the computerized image analyzer (Visioline VL650, CK electronic GmbH, Germany), the total wrinkle area, max wrinkle depth, mean depth and mean And length (mean length).

4) Immunohistochemical staining of skin tissue

Hematoxylin and eosin (H & E) and Masson's trichrome (M & T) were stained with light microscope (IX71, Olympus, JPN ), And then photographed using a digital camera (DP71, Olympus, JPN).

5) RT-PCR analysis

The tissue was pulverized by adding 1 ml of Trizol solution per 0.1 g of skin tissue, and centrifuged at 4, 12,000 xg for 10 minutes. The supernatant was transferred to a new tube and 200 μl of chloroform was added and vortexed. This process was repeated twice, and the supernatant was transferred to a new tube, and isoprophanol and supernatant were added at a ratio of 1: 1. After 10 minutes of shaking, the mixture was allowed to stand at room temperature for 15 minutes and centrifuged at 12,000 xg for 10 minutes. After removing the supernatant, 1 ml of 70% ethanol was added to the remaining precipitate and the mixture was centrifuged at 7,500 xg for 4 to 5 minutes And centrifuged. After removing the ethanol, the tube containing the RNA precipitate was dried at room temperature for 15 minutes, and the RNA pellet was dissolved using nuclease free water. The concentration of RNA extracted at 260 nm and 280 nm wavelength was measured using a UV / VIS spectrophotometer (Beckman coulter, DU730) and agarose gel electrophoresis was performed to confirm the integrity of the RNA sample.

(GIBCO BRL, Gaithersburg, Md., USA). The reverse transcription was performed using oligo dT primer and superscript reverse transcriptase (GIBCO BRL, Gaithersburg, MD, USA). PCR was carried out using 5 'and 3' flanking sequences of the cDNA to be amplified as a template, using the cDNA obtained from the reverse transcription as a template. The primer sequences used at this time are shown in Table 2. 1 μl of the amplified PCR product was electrophoresed on 1% agarose gel to confirm the DNA band.

The primer sequences used for RT-PCR gene primer The sequence (5 '- > 3') Annealing temperature
(° C) PCR product
(bp) Collagen type I
alpha1 (Col1? 1) F ggcaacagtcgcttcaccta
(SEQ ID NO: 1) 55 164 R agtccgaattcctggtctgg
(SEQ ID NO: 2) Collagen type I
alpha2 (Col1? 2) F cggttctgttggtcctgttg
(SEQ ID NO: 3) 55 103 R acccctgtgccctttatcac
(SEQ ID NO: 4) Collagen type Ⅲ
alpha1 (Col3? 1) F taaccaaggctgcaagatgg
(SEQ ID NO: 5) 55 104 R accagtgcttacgtgggaca
(SEQ ID NO: 6) Matrix
metallopeptidase 1a (MMP-1a) F ccctgtgtttcacaacggag
(SEQ ID NO: 7) 55 133 R cctcagcttttcagccatca
(SEQ ID NO: 8) Matrix
metallopeptidase 1b (MMP-1b) F tttgctcatgcttttctgcc
(SEQ ID NO: 9) 55 146 R gaatgggagagtccaaggga
(SEQ ID NO: 10) Matrix
metallopeptidase 3 (MMP-3) F tgctggtatggagcttctgc
(SEQ ID NO: 11) 55 142 R catctccaacccgaggaact
(SEQ ID NO: 12) Matrix
metallopeptidase 9 (MMP-9) F gtggaccatgaggtgaacca
(SEQ ID NO: 13) 55 102 R actgcacggttgaagcaaag
(SEQ ID NO: 14) Glyceraldehyde
3-phosphate
dehydrogenase
(GAPDH) F ggagattgttgccatcaacg
(SEQ ID NO: 15) 55 122 R tgacaagcttcccattctcg
(SEQ ID NO: 16)

2-2. Experiment result

1) Weight and dietary intake of reckless mice

UV irradiation, cadaverine, and vitamin C intake did not significantly affect body weight and dietary intake of reared mice (Fig. 2). The values in Figure 2 are the mean ± SEM of 5 mice.

2) Changes in water content, elasticity and erythema index of ultraviolet irradiated mouse skin

In the + UVB control group irradiated with ultraviolet light for 10 weeks, the water content and elasticity of the skin tissue were significantly decreased while the moisture evaporation and erythema index were significantly increased compared with the normal UV group (-UVB) 3). In the case of cadaverine-fed group (CV), water content and elasticity were significantly increased by 99% and 89%, respectively, compared with the + UVB control group, while the water evaporation and erythema indexes were 50 % And 29%, respectively. The water content and elasticity-enhancing effect of cadaverine was similar to or better than that of vitamin (Fig. 3). The values in FIG. 3 are the mean ± SEM of 5 mice, and the alphabet on the bar represents a significant difference by one-way ANOVA followed by Duncan's multiple range test (p <0.05).

3) Changes in skin wrinkle formation in ultraviolet irradiated mice

To evaluate the effect of cadaverine ingestion on the degree of skin wrinkles, the back skin area of the experimental animals was photographed. The UVB-irradiated control group, which was exposed to UVB for 10 weeks, was observed visually for the formation of fine wrinkles with a large number of coarse and deep wrinkles, compared to the non-irradiated normal group (-UVB) + UVB control group, it was confirmed that the wrinkles were significantly reduced in thickness and depth and improved in a similar manner to the skin condition observed in the un-irradiated-UVB group (FIG. 4).

As a result of the measurement of the degree of wrinkle formation, the + UVB control group was thicker and deeper than the non-UV irradiated normal group (-UVB) It was observed that fine wrinkles were formed with wrinkles. In the case of the cadaverine-supplemented group, it was confirmed that the thickness and depth of the wrinkles were remarkably improved, such that deep wrinkles almost disappeared compared with the + UVB control group, (Fig. 5A). In the CV group, the total wrinkle area was 53%, the maximum wrinkle depth was 51%, the average wrinkle depth was 36%, and the average wrinkle area The length was significantly reduced by 64%, and the wrinkle-reducing effect of such cadaverine was similar to the wrinkle-reducing effect observed in vitamin C (Fig. 5B). Values in FIG. 5B are mean ± SEM of 5 mice, and the alphabet on 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 the ingestion of cadaverine has an effect of remarkably suppressing the generation of wrinkles by ultraviolet irradiation.

4) Changes in skin thickness of ultraviolet irradiated mice

As the photoaging by ultraviolet rays proceeds, the formation of the stratum corneum is increased to thicken the skin to protect the skin dermis layer, and thus the thickness of the skin skin layer is increased by ultraviolet irradiation, which means that skin damage due to photoaging is large J Molecular mechanism of skin aging Mech Ageing Dev 123: 801-810, 2002)

On the last day of the experiment, the thickness of the back skin was measured using a digital micro caliper. As a result, the + UVB control group showed a significant increase in skin thickness compared with the UV group (-UVB) Lt; RTI ID = 0.0 > UVB < / RTI > control group (FIG. 6A). The values in FIG. 6A are the mean ± SEM of 5 mice and the alphabets on the bar represent significant differences by one-way ANOVA followed by Duncan's multiple range test (p < 0.05).

As a result of H & E staining of the skin tissue, skin thickness of the skin of the untreated mice was observed. In the + UVB control group, the skin epidermal layer was thickened compared to the normal unirradiated group (-UVB) (Fig. 6B). As shown in Fig.

5) Quantity and morphology of collagen fibers in dermal layer of ultraviolet irradiated mice

In the case of skin that has undergone photoaging by ultraviolet irradiation, the collagen fiber network of the epidermal-dermal binding site is damaged, and therefore the amount and shape of the collagen fiber is used as a skin photoaging index (Varani et al., "Inhibition of type I procollagen synthesis damaged collagen in photoaged skin and collagenase-degraded collagen in vitro. "The American Journal of pathology 158: 931-942, 2001). Ultrastructural examination of collagen fibers stained with Masson's trichrome showed that the anionic blue-colored collagen fibers were observed in the dermal layer under the epidermis of the UVB group, but UVB In the UVB group were weakly stained with aniline blue. In the dermal layer of cadaverine for 10 weeks with UVB irradiation, the densities of the collagen fibers were relatively dense, the arrangement was regular, and the degree of dyeing by aniline blue was stronger than that of the control group. (Fig. 7).

6) Changes in gene expression in ultraviolet irradiated mouse skin

Collagen type 1 and 3 are proteins that constitute the epidermal component of the dermal layer. In particular, type 1 collagen is present in the largest amount among the extracellular matrix proteins present in the connective tissue of the skin. Meanwhile, 23 types of MMPs catalyzing collagen degradation exist in mammals. MMP types 1, 3 and 9 are known to increase by ultraviolet rays. These three types of MMPs are enzymes that degrade collagen type 1 and 3 to be. It is known that MMP-1 cleaves the middle of collagen fibers while MMP-3 and MMP-9 cleave the cut collagen fibers (Quan T. et al., Elevated matrix metalloproteinases and collagen fragmentation J Dermatological Science 23: S30-S36, 2000). In this study, we have investigated the effects of various types of cytokines in human dermal fibroblast.

As a result of RT-PCR analysis of gene expression in skin tissues, it was found that the + UVB control group had higher collagen type 1α1 and α2, and collagen type 3α1 (compared to -UVB) Expression of MMP-1a and -1b, MMP-3, and MMP-9 gene were significantly increased. On the other hand, the expression of collagen type 1α1 and α2 and collagen type 3α1 was significantly increased in the cadaverine-fed group compared to the + UVB control group, and the expression of MMP-1a and -1b, MMP-3 and MMP-9 gene (Fig. 8). Therefore, it is considered that cadaverine inhibits the formation of wrinkles by irradiation of ultraviolet rays by increasing collagen protein synthesis in skin tissue and inhibiting decomposition of collagen fiber.

These results suggest that cadaverine has an effect of preventing or alleviating skin wrinkles caused by ultraviolet rays and suggests that it can be usefully used as functional cosmetics, health functional foods, medicines or quasi-drugs in the future.

Skin wrinkle improvement, skin irritation and skin exfoliation sensation test

3-1. Nutritional cream containing cadaverine ( Experimental Example 1) and Preparation of nourishing cream without cadaverine (Comparative Example 1)

number ingredient Experimental Example 1 (% by weight) Comparative Example 1 (% by weight) One Cetearyl alcohol 1.5 1.5 2 Glyceryl stearate One One 3 Polysorbate 60 1.2 1.2 4 Sorbitan sesquioleate 0.3 0.3 5 Cetyl octanoate 6 6 6 Squalane 8 8 7 Apricode kernel oil 4 4 8 Dimethicone One One 9 Butylene glycol 5 5 10 glycerin 4 4 11 Magnesium aluminum silicate 0.2 0.2 12 Xanthan gum 0.05 0.05 13 antiseptic a very small amount a very small amount 14 Purified water Balance Balance 15 Cadaverine One -

Of the components identified by the respective component numbers in Table 3, components 1 to 8 are first melted by heating at a temperature of 70, and then components 9 to 13 are dissolved and dispersed in component 14 and heated to 70 to emulsify. Thereafter, the emulsified product was cooled to a temperature of 56 ° C, and the component 15 dissolved in the separated component 9 was added and stirred, followed by cooling at room temperature.

In Comparative Example 1 of Experimental Example 1, the composition and manufacturing method were the same except that the component 15, cadaverine, was prepared.

3-2. Wrinkle improvement effect and skin irritation sensory test

In order to evaluate the skin wrinkle improving effect and skin irritation of the cosmetic composition according to the present invention, a sensory test was performed using the nutritional cream prepared in Experimental Example 1 and Comparative Example 1 in Table 3 above.

Specifically, in order to measure the effect of improving the wrinkles of the skin when the nutritional cream of Experimental Example 1 and Comparative Example 1 shown in Table 3 were respectively applied to skin, 20 women of 20 to 50 years age group 3 Experimental Example 1 Nutritive creams (test group) were used, and on the right side of the face, Comparative Example 1 nutrient cream (control group) shown in Table 3 was continuously used for 12 weeks once a day.

In the sensory test, the effect of improving the wrinkles of the skin was relatively evaluated based on the nutritional cream of Comparative Example, and the sensory evaluation of skin irritation was caused by the itching, And so on. The evaluation was carried out in accordance with the blotting law standards of excellent (5 points), excellent (4 points), normal (3 points), poor (2 points), and very poor (1 point) Respectively. In Table 4, skin irritation indicates that the higher the score, the less skin irritation.

number Skin irritation wrinkle improvement Experimental Example 1 Comparative Example 1 Experimental Example 1 Comparative Example 1 One 5 5 4 3 2 4 5 4 5 3 4 4 5 4 4 4 5 5 3 5 5 4 4 5 6 3 4 5 4 7 5 4 5 5 8 4 3 4 4 9 5 5 4 4 10 5 5 5 4 11 5 5 5 5 12 4 4 3 3 13 5 5 4 3 14 4 5 5 5 15 5 4 5 4 16 4 4 5 5 17 5 5 4 4 18 4 4 3 4 19 4 4 4 3 20 3 4 4 3 Average 4.35 4.4 4.35 4.0

As shown in the above Table 4, the skin irritation evaluation score for the nutritional cream formulation of Experimental Example 1 containing cadaverine was very goodly evaluated as 4.35 points, and as in the nutritional cream formulation of Comparative Example 1 which received 4.4 points, It was confirmed that the degree of irritation was low and skin safety was excellent.

In addition, the relative skin wrinkle reducing effect of the nutritional cream formulation of Experimental Example 1 containing cadaverine in comparison with the nutritional cream formulation of Comparative Example 1 was 4.35 in the evaluation score and the degree of wrinkle improvement was also excellent.

Therefore, the cosmetic composition containing the cadaverine or a cosmetically acceptable salt thereof of the present invention as an active ingredient has no skin side effects, has an excellent effect of improving skin wrinkles, increasing the synthesis of collagen proteins and inhibiting the degradation of collagen fibers, Excellent for wrinkle improvement.

3-3. skin Moisture power Increased measurement test

In order to measure the moisture holding ability of the skin when the nutritional cream of Experimental Example 1 and Comparative Example 1 shown in Table 3 were respectively applied to the skin, 20 women in the 20s to 50s of age group were observed on the left side of Table 3 Experimental Example 1 A nutritive cream (test group) was applied to the right side of the face and a nutritive cream (control group) of Comparative Example 1 of Table 3 was gently massaged in a sufficient amount. Massage was carried out evenly over a minute.

Skin moisture content was measured by using a coneometer in a constant temperature and humidity room at room temperature 25 and relative humidity 45% before application. The skin moisture content was measured in Experimental Example 1 and Comparative Example 1 of Table 3 on the left and right sides of the face, respectively After resting for 10 minutes after application, skin moisture was measured 12 hours after application and 24 hours after application. The moisture content of the skin was measured using a coneometer (CM820, Courage Khazaka electronic GmbH, Germany) which measures the moisture content of the skin by measuring the skin's electric capacity according to the moisture content of the skin. The coneometer measures the amount of moisture present in the epidermis of the skin by measuring the degree of ion of water using a sensor and numerically expressing the amount of water to calculate the amount of moisture, and the measurement method is as follows.

1) A coneometer probe was placed on the skin area to be measured.

2) When the probe is pressed onto the skin, the electrical conductivity of the skin is quantified through the sensor and displayed on the screen.

3) Measurement was repeated with different measurement sites.

4) After the measurement, the sensor was wiped with a tissue paper such as a kim wipe and then measured again.

The measured values are shown in Table 5 as average values.

exam
matter Skin moisture (%) Before application After 12 hours After 24 hours Experimental Example 1 30.2 45.6 40.3 Comparative Example 1 30.5 38.7 31.4

As shown in the above results, when the nutritional cream of the comparative example was applied, the skin moisture amount was increased to some extent after 12 hours of application, but it returned to the level similar to that before application after 24 hours. On the other hand, when the nutritional cream of Experimental Example 1 containing cadaverine was applied to the skin, it was confirmed that the moisturizing power lasted more than 24 hours and the skin moisture increase effect was also higher than that of Comparative Example 1.

3-4. Skin exfoliation effect test

In order to measure the skin exfoliation effect when the nutritional cream of Experimental Example 1 and Comparative Example 1 shown in Table 3 were respectively applied to the skin, 20 women of 20 to 50 years age group were given Experimental Example 1 A nutritive cream (test group) was applied to the right side of the face and a nutritive cream (control group) of Comparative Example 1 of Table 3 was gently massaged in a sufficient amount. Massage was carried out evenly over a minute.

Skin mass mass was measured using a Charm view (Moritex, Japan) in a temperature and humidity room at room temperature 25 and relative humidity 45% before application, and the initial skin angular mass was measured. Were applied to the left and right sides of the face, respectively, and then the mass of the skin was measured 24 hours later, and the skin keratin reduction amount was calculated. Each value is shown in Table 6 as an average value.

exam
matter Skin mass (%) Before application After 24 hours Skin keratin reduction Experimental Example 1 20.1 9.8 10.3 Comparative Example 1 19.9 16.3 3.6

As shown in the above results, it was confirmed that the nutritional cream of Experimental Example 1 containing cadaverine is superior to the nutritional cream of Comparative Example 1 which does not contain cadaverine, in reducing skin deadening. As the moisturizing effect is given to the skin, each mass decreases. The nutritional cream of Experimental Example 1 is superior to the nutritional cream of Comparative Example 1 due to excellent moisture retention ability as demonstrated in Example 3-3 above. .

[ Manufacturing example 1] Manufacture of cosmetics

1-1. Production of flexible lotion

A flexible lotion containing cadaverine was prepared with the composition shown in Table 7 below.

Furtherance Manufacturing example 1-1 ( weight% ) Cadaverine 0.1 ethanol 10.0 Polyoxyethylene sorbitan polylauric acid 1.0 Paraoxybenzoic acid methyl 0.2 glycerin 5.0 1,3-butylene glycol 6.0 incense Suitable amount Pigment Suitable amount

1-2. Manufacture of nutrition lotion

Nutritional lotion containing cadaverine was prepared with the composition of Table 8 below.

Furtherance Manufacturing example 1-2 ( weight% ) Cadaverine 0.05 Vaseline 2.0 Sesquioleic acid sorbitan 0.8 Polyoxyethylene oleylethyl 1.2 Paraoxybenzoic acid methyl Suitable amount Propylene glycol 5.0 ethanol 3.2 Carboxyvinyl polymer 18.0 Potassium hydroxide 0.1 Pigment Suitable amount incense Suitable amount

1-3. Manufacture of nutrition cream

Nutritive creams containing cadaverine were prepared with the compositions of Table 9 below.

Furtherance Manufacturing example 1-3 (wt%) Cadaverine 0.2 Stearic acid 15.0 Cetanol 1.0 Potassium hydroxide 0.7 glycerin 5.0 Propylene glycol 3.0 antiseptic Suitable amount incense Suitable amount Purified water to 100

1-4. Manufacture of packs

A pack containing cadaverine was prepared with the composition of Table 10 below.

Furtherance Manufacturing example 1-4 ( weight% ) Cadaverine 0.05 glycerin 5.0 Propylene glycol 4.0 Polyvinyl alcohol 15.0 ethanol 8.0 Polyoxyethylene oleyl ether 1.0 Paraoxybenzoic acid methyl 0.2 Pigment Suitable amount incense Suitable amount

1-5. Manufacture of essences

Essences containing cadaverine were prepared with the composition shown in Table 11 below.

Furtherance Manufacturing example 5 (% by weight) Comparative Example 5 (% by weight) Cadaverine 0.2 - Propylene glycol 10.0 10.0 glycerin 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 5.0 ethanol 5.0 5.0 Polyoxyethylene hardened castor oil 1.0 1.0 Paraoxybenzoic acid methyl 0.1 0.1 incense Suitable amount Suitable amount Purified water to 100 to 100

[ Manufacturing example 2] Manufacture of health functional foods

2-1. Manufacture of Health Functional Foods

Health functional foods containing cadaverine were prepared with the composition shown in Table 12 below.

Furtherance Manufacturing example 2-1 Cadaverine 1000 mg Vitamin mixture Suitable amount 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 [mu] g Vitamin B12 10 mg Vitamin C 10 [mu] g Biotin 1.7 mg Nicotinic acid amide 50 [mu] g Folic acid 0.5 mg Calcium pantothenate Suitable amount Mineral mixture Suitable amount Ferrous sulfate 1.75 mg Zinc oxide 0.82 mg Magnesium carbonate 25.3 mg Potassium monophosphate 15 mg Dibasic potassium phosphate 55 mg Potassium citrate 90 mg Calcium carbonate 100 mg Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a component suitable for a health functional food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above components may be mixed The granules can then be prepared and used in the manufacture of a health functional food composition according to conventional methods.

2-2. Manufacture of health drinks

Health drinks containing cadaverine were prepared with the compositions of Table 13 below.

Furtherance Manufacturing example 2-2 (mg) Cadaverine 1000 mg Citric acid 1000 mg oligosaccharide 100 g Plum concentrate 2 g Taurine 1 g Purified water Suitable amount

The above components were mixed according to a conventional health drink manufacturing method, and the resulting solution was stirred and heated at 85 for about 1 hour. The resulting solution was filtered and sterilized in 21 containers for sterilization, and then stored in the refrigerator. Beverage composition. Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the compounding ratio may be arbitrarily varied depending on the regional and national preferences such as the demand level, the demanding country, and the intended use.

2-3. Manufacture of tablets

Tablets containing cadaverine were prepared by tableting according to a conventional tablet preparation method with the composition shown in Table 14 below.

Furtherance Manufacturing example 2-3 (mg) Cadaverine 100 mg Corn starch 100 mg Lactose 100 mg Magnesium stearate 2 mg

2-4. Preparation of capsules

The composition of the following Table 15 was filled in gelatin capsules according to a conventional capsule preparation method to prepare capsules containing cadaverine.

Furtherance Manufacturing example 2-4 (mg) Cadaverine 100 mg Corn starch 100 mg Lactose 100 mg Magnesium stearate 2 mg

2-5. Manufacture of rings

In the composition shown in the following Table 16, a ring was prepared so as to be 4 g per one ring according to a conventional ring production method.

Furtherance Manufacturing example 2-5 (mg) Cadaverine 1 g Lactose 1.5 g glycerin 1 g Xylitol 0.5 g

2-6. Manufacture of granules

In the composition shown in Table 17 below, 100 mg of 30% ethanol was added and dried at 60 ° C. to form granules, which were then filled into bins to prepare granules.

Furtherance Manufacturing example 2-6 (mg) Cadaverine 150 mg Soybean extract 50 mg glucose 200 mg Starch 600 mg

[ Manufacturing example 3]

Manufacture of ointment for external skin

An ointment for external use containing cadaverine was prepared with the composition shown in Table 18 below.

Furtherance Manufacturing example 6 ( weight% ) Cadaverine 0.5 Diethyl sebacate 8.0 Nonsense 5.0 Polyoxyethylene oleyl ether
Phosphate 6.0 Sodium benzoate Suitable amount

<110> Industry-Academic Cooperation Foundation, Yonsei University <120> Composition comprising cadaverine or salt thereof <130> 1060478 <160> 16 <170> Kopatentin 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 1 forward primer <400> 1 ggcaacagtc gcttcaccta 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 1 reverse primer <400> 2 agtccgaatt cctggtctgg 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 2 forward primer <400> 3 cggttctgtt ggtcctgttg 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 1 alpha 2 reverse primer <400> 4 acccctgtgc cctttatcac 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 3 alpha 1 forward primer <400> 5 taaccaaggc tgcaagatgg 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Collagen type 3 alpha 1 reverse primer <400> 6 accagtgctt acgtgggaca 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-1a forward primer <400> 7 ccctgtgttt cacaacggag 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-1a reverse primer <400> 8 cctcagcttt tcagccatca 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-1b forward primer <400> 9 tttgctcatg cttttctgcc 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-1b reverse primer <400> 10 gaatgggaga gtccaaggga 20 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-3 forward primer <400> 11 tgctggtatg gagcttctgc 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-3 reverse primer <400> 12 catctccaac ccgaggaact 20 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-9 forward primer <400> 13 gtggaccatg aggtgaacca 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MMP-9 reverse primer <400> 14 actgcacggt tgaagcaaag 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> GAPDH forward primer <400> 15 ggagattgtt gccatcaacg 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> GAPDH reverse primer <400> 16 tgacaagctt cccattctcg 20

Claims

A cosmetic composition having a skin moisturizing effect, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement or skin photoaging improvement effect containing cadaverine or a cosmetically acceptable salt thereof as an active ingredient.

The cosmetic composition according to claim 1, wherein the cadaverine or a cosmetically acceptable salt thereof is contained in an amount of 0.0001 to 20% by weight based on the total weight of the composition.

The composition according to claim 1, wherein the composition is at least one selected from the group consisting of a skin lotion, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizer, a nutrition lotion, a massage cream, a nutritional cream, And is characterized in that it is made of any one of the formulations selected from the group consisting of mask sheet, exfoliating agent, soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder and eye shadow / RTI >

The cosmetic composition according to claim 1, wherein the composition further comprises a skin wrinkle improving component.

[Claim 5] The method of claim 4, wherein the skin wrinkle improving component further comprises at least one member selected from the group consisting of vitamin C, retinoic acid, transforming growth factor (TGF), protein from animal placenta, betulinic acid and chlorella extract &Lt; / RTI >

A health functional food composition having skin moisturizing effect, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement or skin photoaging improvement effect containing cadaverine or a pharmaceutically acceptable salt thereof as an active ingredient.

The health functional food composition according to claim 6, wherein the composition is one selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings.

7. The health functional food composition according to claim 6, wherein the composition further comprises a skin wrinkle improving ingredient.

[Claim 9] The method of claim 8, wherein the skin wrinkle improving component further comprises at least one selected from the group consisting of vitamin C, retinoic acid, transforming growth factor (TGF), protein from animal placenta, betulinic acid and chlorella extract Wherein said composition is a food composition.

A quasi-product composition having skin moisturizing, skin exfoliation, skin elasticity enhancement, erythema suppression, skin wrinkle improvement or skin photoaging improvement effect containing cadaverine or a salt thereof as an active ingredient.