KR102022620B1 - Composition for improving skin wrinkle comprising spinosin - Google Patents

Abstract

The present invention relates to a composition for improving skin wrinkles containing spinosin or an acceptable salt thereof as an active ingredient. In particular, the composition containing the spinocin as an active ingredient showed an excellent elastinase inhibitory effect compared to the adenosine itself used as a positive control, and had anti-wrinkle activity when applied to artificial skin with UVB. Therefore, the composition containing the spinocin as an active ingredient may be usefully used as a composition for improving skin wrinkles, a cosmetic composition, an external preparation for skin wrinkles or a health functional food.

Description

Composition for improving skin wrinkle comprising spinosin

The present invention relates to a composition for improving skin mains containing spinosin or an acceptable salt thereof as an active ingredient. Specifically, cosmetic composition for improving skin wrinkles comprising spinosine or an acceptable salt thereof as an active ingredient; Skin external preparations containing spinosine or an acceptable salt thereof as an active ingredient; Health functional food for improving skin wrinkles comprising spinosine or a food acceptable salt thereof as an active ingredient; Pharmaceutical composition for preventing or treating skin wrinkles, comprising spinosine or a pharmaceutically acceptable salt thereof as an active ingredient; And it relates to a quasi-drug composition for the prevention or improvement of skin wrinkles, comprising a spinocin or a pharmaceutically acceptable salt thereof as an active ingredient.

In general, skin wrinkles are known to be produced by various factors such as the moisture content of the skin, the content of collagen, and the ability to act on the external environment. Among the above, collagen is known to have the greatest effect on the formation of skin wrinkles. have.

Collagen is mostly present in the dermal layer of the skin and accounts for about 70-80% of the total dry weight of the skin, supporting most of the extracellular matrix. However, biosynthesis of collagen is reduced by internal factors such as decrease of cellular activity due to natural aging, and the decomposition of collagen is accelerated by the increase of stress caused by harmful environment and external factors such as sun rays, and the skin substrate is destroyed. Wrinkles are created. Therefore, much research has been conducted on active ingredients that can prevent and improve such phenomena.

Elastase, which is present in human neutrophil granulocytes, is an enzyme that degrades elastin, a substrate protein important for maintaining skin elasticity in the dermis, and a nonspecific hydrolase that can degrade collagen, another important substrate protein. If elastinase is properly expressed and activated, blood thrombosis or wound may be involved in wound recovery, but if excessively expressed or activated, elastin in the skin may be broken down to lose elasticity of the skin. Therefore, an elastinase inhibitor has an effect of improving skin wrinkles, and ursolic acid is used as an elastinase inhibitor.

In order to improve skin wrinkles, jujube red duck mushroom fermentation broth having an activity against anti-aging and wrinkle improvement and pharmaceutical and raw materials containing the same as an active ingredient (Korea Patent 10-1578908), skin elasticity enhancement or wrinkle improvement including herbal extract Efforts have been made to find a composition for improving skin wrinkles in extracts containing various components, such as cosmetic compositions (Korean Patent Publication No. 10-2016-003918). However, a composition for improving skin wrinkles has been developed that includes only a single component showing an effective effect of improving skin wrinkles among various components of the extract and has a satisfactory stability and wrinkle improvement effect.

Spinosine is a compound having molecular formula C28H32O15, molecular weight 608.549 g / mol, which is 2 ''-O-glycosylswertisin, or 6-[(2S, 3R, 4S, 5S, 6R) -4,5-dihydroxy-6- (hydroxymethyl ) -3-[(2S, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy-6- (hydroxymethyl) oxan-2-yl] oxyoxan-2-yl] -5-hydroxy-2- ( It is also named 4-hydroxyphenyl) -7-methoxychromen-4-one. Although the specific pharmacological activity of the spinosine is still under study, it is not known whether it has a direct skin wrinkle improvement effect.

Against this background, the present inventors conducted a study on a material having an excellent skin wrinkle improvement effect, and found that a composition containing spinosine as an active ingredient inhibits elastinase to inhibit elastin and collagen degradation and increase collagen biosynthesis. By clarifying, the present invention has been completed, which is excellent in safety and excellent in improving skin wrinkles.

One object of the present invention is to provide a composition for improving skin wrinkles comprising spinosine (spinosin) or an acceptable salt thereof as an active ingredient.

Still another object of the present invention is to provide a skin external preparation for improving skin wrinkles comprising spinosine or an acceptable salt thereof as an active ingredient.

Still another object of the present invention is to provide a cosmetic composition for improving skin wrinkles comprising spinosine or a cosmetically acceptable salt thereof as an active ingredient.

Still another object of the present invention is to provide a health functional food for improving skin wrinkles comprising spinosine or a food acceptable salt thereof as an active ingredient.

Still another object of the present invention is to provide a quasi-drug composition for preventing or improving skin wrinkles, which comprises spinosine or a pharmaceutically acceptable salt thereof as an active ingredient.

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

Meanwhile, each of the descriptions and the embodiments disclosed herein may be applied to each of the other descriptions and the embodiments. That is, all combinations of the various elements disclosed herein are within the scope of the present invention. In addition, the scope of the present invention is not limited by the specific description described below.

In addition, one of ordinary skill in the art can recognize or identify numerous equivalents to certain aspects of the invention described in this application using conventional experiments only. Also, such equivalents are intended to be included in the present invention.

As one embodiment for achieving the above object, the present invention provides a cosmetic composition for improving skin wrinkles comprising a spinosin (spinosin) or a cosmetically acceptable salt thereof as an active ingredient.

In the present invention, "Spinosine" is a compound having the molecular formula C ₂₈ H ₃₂ O ₁₅ , molecular weight 608.549 g / mol, represented by the formula (1), 2 ''-O-glycosylswertisin, or 6-[(2S, 3R, 4S, 5S, 6R) -4,5-dihydroxy-6- (hydroxymethyl) -3-[(2S, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy-6- (hydroxymethyl) oxan-2 It is also named -yl] oxyoxan-2-yl] -5-hydroxy-2- (4-hydroxyphenyl) -7-methoxychromen-4-one. The specific pharmacological activity of the spinocin is still under study, but it is not known whether it has a direct skin wrinkle improvement effect.

Spinosine represented by Formula 1 of the present invention may exist in unsolvated form as well as in solvated form. Spinosine of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.

In the present invention, "wrinkle" means a fine line caused by the skin is decayed, it may be caused by the cause of the gene, the reduction of collagen present in the dermis of the skin, the external environment. The wrinkles may include skin aging or skin elasticity reduction. The skin aging refers to the type and intangible changes that appear on the skin with age, as well as endogenous aging (natural aging) that occurs with everyone without special environmental factors, as well as stress, ultraviolet rays, smoking, drug use, etc. It may include all of the exogenous aging that occurs as a cause.

In one embodiment of the present invention, as a result of confirming the inhibitory effect of spinosine on the activity of elastinase related to skin wrinkle formation, the compound showed an effect of reducing elastinase activity, in particular, used as a positive control Adenosine-like elastinase activity was reduced. Therefore, it was confirmed that the composition containing spinosine can be used as a composition for improving skin wrinkles, cosmetic composition, external preparation for skin, health functional food, pharmaceutical composition for preventing or treating wrinkles and quasi-drug composition for preventing or improving wrinkles (FIG. 1). .

In another embodiment of the present invention, the anti-wrinkle activity according to the photoaging of spinosine was evaluated in artificial skin (3D human skin). As a result of the experiment, it was confirmed that the amount of collagen in the skin was reduced due to the lightening of the blue dye in the skin with UVB (FIG. 2). Therefore, it was confirmed that the composition containing spinocin can be used as a composition for improving skin wrinkles, cosmetic compositions, skin external preparations, health functional foods, pharmaceutical compositions for preventing or treating wrinkles, and quasi-drugs for preventing or improving wrinkles. .

The cosmetic composition according to the present invention is a solution, external ointment, cream, foam, nourishing lotion, softening lotion, pack, softening water, latex, makeup base, essence, soap, liquid cleansing agent, bath, sunscreen cream, sun oil, suspension, Emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays may be prepared in a formulation selected from the group consisting of, but not limited to It is not.

In the present invention, "cosmetic acceptable salt" is a form of a salt in which the spinocin is combined with other substances, it means a substance that can exhibit a cosmetically similar activity to the spinocin.

In addition, the cosmetic composition of the present invention may further include one or more cosmetically acceptable carriers formulated in general skin cosmetics, and as conventional components, for example, oil, water, surfactants, moisturizers, lower alcohols, Thickeners, chelating agents, pigments, preservatives, flavoring agents, and the like may be appropriately blended, but are not limited thereto.

The cosmetically acceptable carrier included in the cosmetic composition of the present invention varies depending on the dosage form.

When the formulation of the present invention is an ointment, paste, cream or gel, the carrier component may be animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures of these may be used.

If the formulation of the invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or mixtures thereof may be used, in particular in the case of a spray additionally chloro Propellants, such as fluorohydrocarbons, propane / butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, solvents, solubilizers or emulsions are used as carrier components, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil may be used, in particular cottonseed oil, peanut oil, corn seed oil, olive oil, castor oil and sesame oil, fatty acid esters of glycerol aliphatic ester, polyethylene glycol or sorbitan may be used. have.

When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, micro Crystalline cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the present invention is a soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolyzates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars and the like may be used as carrier components. Can be.

Another aspect of the present invention provides a skin external preparation for improving skin wrinkles comprising spinosine or an acceptable salt thereof as an active ingredient.

In the present invention, "spinosine" is as described above.

In the present invention, the "acceptable salt" refers to a substance which is in the form of a salt in which spinosine is combined with another substance, and which can exhibit similar activity as spinosine.

The term "skin external preparation" of the present invention is a general concept encompassing a substance generally used for external application of the skin, and non-limiting examples of the external preparation for skin preparation include PLASTERS, LOTIONS, and lining agents. LINIMENTS, LIQUIDS AND SOLUTIONS, AEROSOLS, EXTRACTS, OINTMENTS, FLUIDEXTRACTS, Emulsions, SUPESIONS, CAPSULES , Creams (CREAMS), soft, hard gelatin capsules, patches, or sustained release agents.

The external preparation for skin according to the present invention may be a parenteral dosage form formulated in the form of a solid, semisolid or liquid by adding a commercially available inorganic or organic carrier, excipient and diluent. For parenteral administration, the preparation may be a transdermal dosage form selected from the group consisting of drops, ointments, lotions, gels, creams, patches, sprays, suspensions and emulsions, but is not limited thereto.

Carriers, excipients and diluents that may be included in the external preparation include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

In the external composition for skin according to each formulation, other ingredients other than the composition of the present invention described above may be appropriately selected and blended by those skilled in the art according to the formulation or use purpose of the external skin preparation, and in this case, simultaneously applied with other raw materials. If you do, synergistic effects may occur.

Another aspect of the present invention provides a functional food for skin wrinkle improvement, comprising spinosine or a food acceptable salt thereof as an active ingredient.

In the present invention, "spinosine" is as described above.

In the present invention, the "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. The term "functional" as used herein 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. In addition, 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 of the present invention can be prepared in various forms of formulation, and unlike the general medicine has the advantage that there is no side effect that can occur when taking long-term use of the drug as a raw material, and excellent portability, the present invention Dietary supplements are available as supplements to enhance skin wrinkles.

The health functional food of the present invention may contain various flavors or natural carbohydrates as additional ingredients. The above-mentioned natural carbohydrates are sugars such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose and polysaccharides such as dextrin and cyclodextrin, xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin, aspartame, and the like can be used.

In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, And a carbonation agent used for the carbonated beverage. These components can be used independently or in combination. The ratio of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health food of the present invention.

Another aspect of the present invention provides a quasi-drug composition for preventing or improving skin wrinkles, which comprises spinosine or a pharmaceutically acceptable salt thereof as an active ingredient.

The composition may also be used as a pharmaceutical composition for preventing or treating skin wrinkles.

In the present invention, "spinosine" is as described above.

In the present invention, the "pharmaceutically acceptable salt" refers to a substance in which spinosine is in the form of a salt in combination with another substance, and which can exhibit pharmacologically similar activity as spinosine.

In the present invention, the "quasi drug" refers to articles that are less active than drugs among those used for the purpose of diagnosing, treating, ameliorating, reducing, treating, or preventing a disease of a human or animal. According to the quasi-drug product, 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.

In the present invention, the "quasi drug composition" may be prepared in a form selected from the group consisting of body cleanser, foam, soap, mask, ointment, cream, lotion, essence and spray, but is not limited thereto.

When the spinosine of the present application is used as an quasi-drug additive, the spinocin of the present application may be added as it is, or may be used together with other quasi-drugs or quasi-drug components, and may be appropriately used according to a conventional method.

The composition comprising the spinosin of the present invention as an active ingredient inhibits the activity of elastinase related to skin wrinkle formation, and in particular, when applied to artificial skin with UVB, the collagen breakdown in the skin is inhibited as well as reduced collagen. The amount was recovered and the collagen synthesis amount was confirmed to increase. Therefore, the composition containing the spinocin as an active ingredient may be usefully used as a cosmetic composition for improving skin wrinkles, a skin external preparation for improving skin wrinkles, or a health functional food.

1 is a graph confirming the effect of inhibiting the elastinase (elastase) of the spinosin (spinosin).
Figure 2 is a graph confirming the effect of inhibiting wrinkles in artificial skin according to the concentration of spinosine.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are only for illustrating the present invention and the scope of the present invention is not limited thereto.

Example  One: Spinocin Elastinase ( elastase ) Inhibition activity measurement

1-1. Spinocin  Produce

Spinosine was purchased from Chem Faces and prepared by diluting spinosine in 0.2M Tris-Cl solution (pH 8.0) in methanol to final concentrations of 0.625, 6.25, 25 and 50 μg / ml.

1-2. Elastinase  Produce

Elastinase was dissolved in 1 ml of 50 mM Tris-Cl solution (pH 8.6) with N-succinyl- (Ala) 3-ρ-nitroanilide (N-succinyl- (Ala) 3). 5 μl of -pnitroanilide) was added to prepare a substrate solution. The enzyme solution was diluted with 0.6 unit / ml of porcine pancreatic elastase (PPE) using 50 mM Tris-Cl solution (pH 8.6). Prepared and prepared.

1-3. Spinocin Elastinase  Inhibition activity measurement

100 μl of spinosine diluted to various concentrations was added to 100 μl of substrate solution and 50 μl of enzyme solution, followed by reaction at 37 to 20 minutes. The reaction was then measured for absorbance at 410 nm using an ELISA reader, and then the elastinase activity (%) was calculated using Equation 2 below. At this time, the group was added methanol instead of spinoic acid, adenosine was used as a comparison group at a concentration of 14μg / ml.

Elastinase inhibitory activity was confirmed by the following formula.

% Elastinase inhibitory activity = {1- (absorbance of sample addition / absorption of no addition)} Ｘ 100

As a result, it was confirmed that the elastinase inhibitory effect increases as the concentration of spinosine increases. In particular, when the concentration of spinosine 50μg / ml was confirmed to bring about the same inhibitory effect as adenosine known as an elastinase activity inhibitor (Fig. 1).

Example  2: Spinocin  Wrinkle Inhibitory Activity in Artificial Skin

Wrinkle improvement effect of spinocin was tested in more detail by experimenting with real artificial skin.

Wrinkle inhibitory activity according to the photoaging of spinosine was evaluated in 3D human skin. Specifically, spinocin was treated for 1 hour before artificial skin to a final concentration of 6.25 μg / ml, 12.5 μg / ml concentration was irradiated with UVB 50mJ / cm ² . After incubation for 2 days in an incubator maintained at 5% CO ₂ , 37 ° C and 95% humidity, the artificial skin was cut and fixed in 4% paraformaldehyde and subjected to tissue processing. block). Paraffin blocks were cut to a thickness of 5 μm and attached to slides, and stained with Masson Trichrome stain. Wrinkle inhibitory activity was evaluated through collagen fibers stained blue through tissue staining.

As a result, as shown in FIG. 2, it was confirmed that the amount of collagen in the skin was reduced due to the thinning of the blue dye in the skin with UVB. In addition, as the concentration of spinosine increases, the blue staining becomes darker than the normal control, which inhibits collagen degradation and increases the amount of collagen synthesized.

Therefore, it can be confirmed that the spinosine has an effect of increasing collagen synthesis in a concentration-dependent manner when applied to the actual skin, and thus has an effective wrinkle improvement activity.

From the above description, those skilled in the art will appreciate that the present invention can be implemented in other specific forms without changing the technical spirit or essential features. In this regard, the embodiments described above are to be understood in all respects as illustrative and not restrictive. The scope of the present invention should be construed that all changes or modifications derived from the meaning and scope of the following claims and equivalent concepts rather than the detailed description are included in the scope of the present invention.

Claims (7)

Spinosine (spinosin) or an acceptable salt thereof as an active ingredient, the composition for preventing or improving skin wrinkles. The composition for improving skin wrinkles according to claim 1, wherein the composition inhibits elastinase activity or collagen breakdown. Spinosine or a cosmetically acceptable salt thereof as an active ingredient, cosmetic composition for improving skin wrinkles. The composition of claim 3, wherein the composition is a solution, cream, foam, nourishing lotion, softening lotion, pack, softening water, makeup base, essence, soap, liquid cleanser, bath, sunscreen cream, sun oil, suspension, emulsion, Cosmetic composition, characterized in that it has a formulation selected from the group consisting of pastes, gels, lotions, powders, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays. A skin external preparation for improving skin wrinkles comprising spinosine or an acceptable salt thereof as an active ingredient. A health functional food for improving skin wrinkles comprising spinosine or a food acceptable salt thereof as an active ingredient. Spinocin or a pharmaceutically acceptable salt thereof as an active ingredient, the quasi-drug composition for preventing or improving skin wrinkles.

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