KR20160123753A - Composition for skin whitening - Google Patents

Abstract

The present invention relates to a composition for improving skin whitening and wrinkles comprising the compound of formula (I) as an active ingredient. The compound of the formula (I) of the present invention is not only excellent in inhibiting melanin production but also promotes collagen synthesis, inhibits collagenase activity, and is excellent in solubility and stability, thus being used as an active ingredient of a composition for skin whitening and wrinkle improvement It is very suitable for the following. Accordingly, the composition of the present invention comprising the compound provides excellent skin whitening and wrinkle-reducing effects.
(I)

Description

 Composition for skin whitening [

 The present invention relates to a composition for improving skin whitening and wrinkles exhibiting excellent melanin production inhibitory activity, collagen synthesis promoting activity and collagenase inhibitory activity.

The skin color of a person is determined by various factors such as the activity of the melanocyte making the melanin pigment, the distribution of blood vessels, the thickness of the skin, and the presence or absence of pigment inside and outside the body such as carotenoid and bilirubin. Among them,

Melanin, a pigment that is formed, is considered to be the most important factor for skin color formation. Melanin is a compound in which tyrosine is converted to melanin by tyrosinase through 3,4-dihydroxyphenylalanine, dopaquinone, leucodipachrome, dopachrome, 5,6-dihydroxyindole, and 5,6- It is the end product of the oxidation process. Melanin biosynthesis is a very complex process, and the exact mechanism by which melanin synthesis is induced is not yet elucidated.

Melanin provides a natural defense against harmful ultraviolet rays, but when melanin is produced, hyperpigmentation such as spots and freckles is induced.

Effective ingredients that suppress skin pigmentation and exhibit a skin whitening effect are known. Materials having tyrosinase inhibitory activity such as arbutin, deoxy arbutin, octadecendanoic acid, conjugated linoleic acid, niacinamide, hydroquinone, kojic acid, glutathione, and azelaic acid have been actually used in whitening products. However, the above-mentioned active ingredients are limited in their use due to insufficient whitening effect, safety to skin, difficulty in formulation and stability, and the like.

Collagen is a major substrate protein produced in the fibroblasts of the skin. Collagen is present in extracellular epilepsy and has important functions such as mechanical rigidity of skin, connective tissue resistance and tissue binding, support of cell adhesion, induction of cell division and differentiation (when organism grows or heals the wound) (Van der Rest et al., 1990). Such collagen is reduced by aging and photoaging by ultraviolet irradiation, which is known to be closely related to wrinkling of the skin (Arthur K. Balin et al., "Aging and the skin ", 1989). In recent years, extensive research into skin aging continues to reveal important functions of collagen in the skin.

In the prior art, there have been products that incorporate collagen into cosmetics from the skin moisturizing effect of collagen, but these cosmetics apply collagen to the skin surface, and since the collagen, which is a polymer, can not be expected to be moisturized by transdermal absorption, Can not be said.

On the other hand, there are known effective substances that promote collagen synthesis and exhibit wrinkle-reducing effects. For example, retinoic acid, transforming growth factor (TGF) (Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974)

(JP8-231370), betulini acid (JP8-208424), chlorella extract (JP9-40523, JP10-36283) and the like derived from animal placenta are known as collagen synthesis promoting substances. However, the above-mentioned effective ingredients are limited in the use amount due to safety problems such as irritation and reddening when applied to the skin, or have insufficient effect, so that there is a problem that the effect of improving skin function by promoting collagen synthesis of skin substantially can not be expected. Therefore, it is safe for living body,

Above all, it is urgently required to develop a composition having a wrinkle-improving activity that is more effective than the existing collagen synthesis promoting substance.

Therefore, it is safe for skin even when used over a long period of time, has physicochemical properties such as solubility suitable for making various formulations, stable without breaking the active ingredient due to heat, light, It is necessary to develop an active ingredient capable of providing a whitening or wrinkle-improving effect even better than that of the present invention. It is therefore an object of the present invention to provide a skin whitening or wrinkle-improving composition comprising the active ingredient having the above-mentioned characteristics.

The present inventors have found that the compound of the formula (I) having a whitening or wrinkle-improving activity, which is safe to the skin and which is easy to produce, and which is stable in cosmetic preparation and storage,

. Accordingly, the present invention provides a composition for improving skin whitening and wrinkles containing the compound of formula (I) as an active ingredient

The compounds of formula (I) of the present invention are not only excellent in inhibiting melanin production, but also have excellent collagen synthesis promoting activity and collagenase inhibiting activity. In addition, the compounds of formula (I) of the present invention have good solubility and stability

And is therefore very suitable for use as an active ingredient of a composition for improving skin whitening and wrinkles. Accordingly, the composition of the present invention comprising the compound provides excellent skin whitening and wrinkle-reducing effects.

The present invention provides a composition for skin whitening comprising a compound of formula (I) as an active ingredient

(I)

In order to exert an excellent whitening effect when the whitening component is applied to actual skin, it exhibits high activity of skin whitening activity at a low concentration, has excellent ability to permeate and absorb the skin, and is volatile so as to stay for a sufficient time to exhibit a whitening effect It is preferable that the active ingredient remains stable on the composition or on the skin, that it is easily formulated into medicines or cosmetics, and that it is safe for the skin. However, among known whitening ingredients, whitening ingredients that satisfy all of the above characteristics are not common. For example, some whitening ingredients are excellent in whitening activity even at a low concentration in an in vitro test, but they are difficult to be applied to real skin because of their ability to be absorbed through the skin. Other whitening ingredients have low hydrophilicity and are difficult to formulate into medicines or cosmetics. In addition, some of the whitening ingredients may be decomposed or transformed into other compounds when exposed to heat, light, or oxygen, leading to the disappearance of the whitening effect prior to application to the skin.

As can be seen in the following examples, the compound of formula (I) exhibits significantly superior melanogenesis inhibitory ability at a low concentration as compared with arbutin, which is a known whitening ingredient. In addition, the solubility of the product in a hydrophilic solvent is high.

Low volatility, superior skin permeability, and easy formulation. In addition, it was shown that the stability was excellent with respect to light, heat or time. In addition, since it shows sufficient whitening effect even at a low concentration,

It was found to be very safe.

Therefore, the compound of formula (I) can be used as an active ingredient exhibiting a whitening effect in medicines or cosmetics. Therefore, the present invention also relates to a pharmaceutical composition for skin whitening or a skin whitening cosmetic composition,

The use of a compound of formula I and an effective amount of a compound of formula I to the skin.

The compound of formula (I) may be synthesized as a known compound or a commercially available compound may be used.

In the present invention, 'whitening' refers to inhibiting, inhibiting or alleviating hyperpigmentation of the skin. Hyperpigmentation of the skin includes freckles, stains, hyperpigmentation after exposure to ultraviolet light, hyperpigmentation after inflammation, aging black spots, brown spots or black spots.

The skin whitening composition of the present invention can provide a desired whitening effect when it contains an effective amount of a compound of formula (I). In the composition for whitening skin of the present invention, the term "effective amount" refers to an amount of the skin whitening composition that inhibits,

Means the amount of compound that can be converted. The effective amount of the compound contained in the composition for skin whitening of the present invention depends on the form in which the composition for skin whitening is commercialized, the method in which the compound is applied to the skin,

It will be different. For example, when the composition for skin whitening is commercialized as a medicament for dermatological treatment according to hyperpigmentation of the skin, the compound of the formula (I) is contained at a higher concentration than the case where it is commercialized as a cosmetic product applied to the skin It will be possible. In the case of a wash-off type cosmetic such as a make-up remover, a detergent and the like in which the active ingredient remains on the skin in a short period of time even when it is commercialized as a cosmetic product, a relatively high concentration of the compound of the formula (I) may be contained. On the other hand, in the case of leave-on type cosmetics such as lotions, creams, essences and the like in which the active ingredient remains on the skin for a long period of time, a low concentration of the compound of the formula (I) It will be acceptable. In one embodiment of the present invention, the skin whitening composition may contain 0.0001% to 10% by weight, based on the total weight of the compound of formula (I). When the skin whitening composition of the present invention contains less than 0.0001% by weight of the compound of the formula I, sufficient whitening effect can not be expected. When the skin whitening composition of the present invention is contained in an amount exceeding 10% by weight, undesired reactions such as allergy occur, To prevent this, there is a problem.

The composition for skin whitening of the present invention may further contain a known whitening ingredient in addition to the compound of the above-mentioned formula (I). If the additional whitening component is included, the whitening effect of the skin whitening composition of the present invention can be further enhanced

to be. When the whitening ingredient is added, skin safety, ease of formulation, and stability of effective ingredients can be taken into account. In one embodiment of the invention, the skin whitening composition is a whitening ingredient known in the art, including arbutin,

May further comprise one or more whitening components selected from the group consisting of oxaliplatin, octadecendionic acid, conjugated linoleic acid, niacinamide, kojic acid, glutathione, embryo canin A, embryo canin B, ascorbic acid and derivatives thereof

have. Additional whitening ingredients may be included in the composition in an amount ranging from 0.0001% to 10% by weight, based on the total weight of the composition, and the weight percent is adjusted according to requirements such as whitening activity, skin safety, ease of formulation with the compound of formula Be able to

will be.

The skin whitening composition of the present invention may further comprise a known sunscreen agent. For example, when the composition for skin whitening of the present invention is formulated into a rib-on type product used during the daytime,

By including the blocking agent, melanin production due to ultraviolet exposure can be inhibited more effectively. The ultraviolet screening agent may be an organic ultraviolet screening agent, an inorganic ultraviolet screening agent, or a mixture thereof. In one embodiment of the invention,

The organic UV blocking agent may be at least one selected from the group consisting of glyceryl paraben, drometrizol, dipalayyl triolate, 3- (4-methylbenzylidene) -camphor, methyl anthranilate, benzophenone- -8, butylmethoxydibenzoylmethane, cyoxsite, ethylhexyltriazone, octocrylene, ethylhexyldimethylphenyl, ethylhexylmethoxycinnamate, ethylhexylsalicylate, p-aminobenzoic acid,

2-phenylbenzimidazole-5-sulfonic acid, homosalate, isoamyl-p-methoxy cinnamate, bishexyloxyphenol methoxyphenyl

(Dimethicone ethyl benzyl triazolate), diallyl dibutyl tin dilaurate, diallyl dibutyl tin dilaurate, diallyl dibutyl tin dilaurate, dibutyl tin dilaurate, Tetramethylbutylphenol, terephthalylidene camphor

Sulfonic acid, and salts thereof. In one embodiment of the present invention, the inorganic UV blocking agent may be at least one inorganic UV blocking agent selected from the group consisting of titanium dioxide, zinc oxide and iron oxide. The ultraviolet screening agent may comprise from 0.1% to 25% by weight based on the total weight of the composition of the present invention. The weight percentages may be adjusted depending on the ultraviolet blocking activity, skin stability, ease of formulation, application of the formulation to be applied to the skin, and the like. For example, when the composition for skin whitening of the present invention is formulated into cosmetics such as lotion, cream, and the like, a sun protection factor (SPF) and a protection grade of UVA (PA) , The weight percentage of the ultraviolet screening agent will be lowered. When the skin whitening composition of the present invention is formulated into a makeup product such as a sunscreen product, a makeup base or a foundation, the SPF and PA values should be set high, The weight percentage of sunscreen in the composition will be high.

Accordingly, the present invention also provides a wrinkle-improving composition comprising the compound of the formula (I) as an active ingredient

In order to exhibit an excellent wrinkle-improving effect when the wrinkle-improving component is applied to the actual skin, it exhibits a high active wrinkle-reducing activity at a low concentration, has an excellent ability to permeate and absorb the skin and can stay for a sufficient time to exhibit a wrinkle- It is preferable to be low in volatility, to stably maintain the active ingredient on the composition or on the skin, to be easily formulated into medicines or cosmetics, and to be safe for the skin. However, among the known wrinkle reducing components, wrinkle reducing components that satisfy all of the above characteristics are not common. For example, some wrinkle-improving ingredients have excellent wrinkle-reducing activity even at low concentrations in vitro, but they are difficult to apply to real skin because of their ability to permeate through the skin. Other wrinkle-reducing ingredients have low hydrophilicity and are difficult to formulate into medicines or cosmetics. In addition, some wrinkle-reducing ingredients may be degraded or transformed into other compounds when exposed to heat, light, or oxygen, which may already wrinkle the skin before application to the skin.

Therefore, the compound of formula (I) can be used as an active ingredient exhibiting anti-wrinkle effect in medicines or cosmetics. The present invention therefore also provides a wrinkle-improving method comprising the use of a compound of formula I for the manufacture of a wrinkle-improving pharmaceutical composition or a wrinkle-improving cosmetic composition and an effective amount of a compound of formula I applied to the skin.

The compound of formula (I) may be synthesized as a known compound or a commercially available compound may be used.

In the composition for improving wrinkles of the present invention, "improving wrinkles" refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating already formed wrinkles.

The wrinkle-improving composition of the present invention can provide a desired wrinkle-improving effect when an effective amount of the compound of the formula (I) is contained. In the composition for improving wrinkles of the present invention, the term "effective amount" means the amount of a compound capable of inhibiting or inhibiting the generation of wrinkles of the skin or relaxing already formed wrinkles. The effective amount of the compound contained in the wrinkle-improving composition of the present invention will vary depending on the form in which the composition for improving wrinkles is commercialized, the method in which the compound is applied to the skin, and the time on the skin. For example, when the wrinkle-improving composition is commercialized as a medicament for dermatological treatment due to the formation of wrinkles of the skin, it may contain a compound of the formula (I) at a higher concentration than the case where it is commercialized as a cosmetic product There will be. In the case of a wash-off type cosmetic such as a make-up remover, a detergent and the like in which the active ingredient remains on the skin in a short period of time even when it is commercialized as a cosmetic product, a relatively high concentration of the compound of the formula (I) may be contained. On the other hand,

In the case of leave-on type cosmetics such as lotions, creams, essences, etc., which stay on the skin for a long period of time, they may contain a lower concentration of the compound of the formula I than the cosmetics of the wash-off type . In one embodiment of the present invention, the wrinkle-improving composition may contain 0.0001% to 10% by weight of the compound of formula (I) based on the total weight of the composition. When the wrinkle-improving composition of the present invention contains less than 0.0001% by weight of the compound of the formula I, sufficient wrinkle-reducing effect can not be expected. When it exceeds 10% by weight, To prevent such a problem.

The wrinkle-improving composition of the present invention may further contain a known wrinkle-improving component in addition to the compound of the above-mentioned formula (I). The addition of the additional wrinkle improving component can further improve the wrinkle improving effect of the composition of the present invention

will be. When the wrinkle-improving ingredient is added, skin safety, easiness of formulation, and stability of effective ingredients can be taken into consideration in combination use. In one embodiment of the present invention, the wrinkle-improving composition is a wrinkle-improving ingredient known in the art and includes at least one wrinkle selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid, and chlorella extract May further comprise an improving component. The additional wrinkle improving component may be included in an amount of 0.0001% to 10% by weight based on the total weight of the composition, wherein said weight% is selected from the group consisting of collagen synthesis promoting or collagenase inhibiting activity, skin safety, And the like of the user.

In the present invention, the composition may be a pharmaceutical composition or a cosmetic composition. When formulating the compositions of the present invention into medicaments or cosmetics, they may contain known dermatologically acceptable excipients which act as carriers for the active ingredient. When formulated as a medicament, the contents disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can be referred to. When formulating into cosmetics, International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association , Inc., Washington, 1995, which is incorporated herein by reference. Which are incorporated herein by reference.

When the composition of the present invention is a cosmetic composition, the composition may include, but is not limited to, a lotion such as a facial lotion, a facial lotion, a body lotion and the like, a cream such as a facial lotion, a body lotion, , Make-up remover, cleansing lotion, cleansing lotion, cleansing foam, soap, body wash such as foundation, powder, cleansing lotion, cleansing oil, cosmetic lotion, spray, gel, pack, sunscreen, makeup base, liquid type, solid type or spray type And the like. In this case, the cosmetic composition may contain at least one kind selected from the group consisting of a surfactant, an emulsifier, a soap acid, a solvent, a colorant, a preservative, an antioxidant, a defoamer, an antibacterial agent, Preservatives, proteins, silicones, solubilizers, sugar derivatives, sunscreens, vitamins, plant extracts, waxes, and the like.

Claims (10)

A composition for skin whitening comprising a compound of formula (I) as an active ingredient.
(I)

The skin whitening composition according to claim 1, wherein the compound of formula (I) is contained in an amount of 0.0001% to 10% based on the total weight of the composition.
The pharmaceutical preparation according to claim 1, which is composed of arbutin, deoxyarbutin, octadecendanoic acid, conjugated linoleic acid, niacinamide, hydroquinone, kojic acid, glutathione, azelphosphoric acid, embryo canin A, embryo canin B, ascorbic acid and derivatives thereof As a group
≪ / RTI > wherein the composition further comprises one or more whitening components selected from the group consisting of: < RTI ID = 0.0 > 4. The composition for whitening skin according to claim 3, wherein the additional whitening component is contained in an amount of 0.0001% to 10% based on the total weight of the composition. The skin whitening composition according to claim 1, further comprising an ultraviolet screening agent. The skin whitening composition according to claim 4, wherein the ultraviolet screening agent is an organic ultraviolet screening agent, an inorganic ultraviolet screening agent, or a mixture thereof. 7. The composition of claim 6, wherein the organic UV blocking agent is selected from the group consisting of octyl methoxycinnamate, octyl salicylate, octocrylene, butyl methoxydibenzoylmethane, oxybenzone, octyltriazone, menthyl anthranilate, 3,4- Wherein the composition is at least one organic sunscreen selected from the group consisting of methyl benzylidene Kemper and bis-ethylhexyloxyphenol methoxyphenyltriazine. 7. The composition for skin whitening according to claim 6, wherein the inorganic UV-blocking agent is at least one inorganic UV-blocking agent selected from the group consisting of titanium dioxide, zinc oxide and iron oxide. The skin whitening composition according to claim 5, wherein the ultraviolet screening agent is present in an amount of 0.1 to 10% by weight based on the total weight of the composition. The composition according to claim 1, wherein the composition for skin whitening is selected from the group consisting of a lotion, an emulsion, a cream, an essence, a cosmetic ointment, a spray, a gel, a pack, a sunscreen, a makeup base, a foundation, a powder, Composition for skin whitening having a formulation