KR101446706B1 - Composition for skin rejuvenation comprising FGF - Google Patents

Abstract

The present invention relates to a cosmetic composition for skin regeneration comprising FGF as an active ingredient for pretreating a carbon enhancer and applying it to laser treated skin. According to the present invention, when the carbon enhancer is applied to the skin and treated with a laser of a specific wavelength, the degree of expression of FGF9 is increased, and the thickness of the dermis and the skin becomes thick, which is effective for skin regeneration.

Description

[0001] The present invention relates to a composition for skin regeneration comprising FGF,

The present invention relates to a cosmetic composition for skin regeneration comprising FGF as an active ingredient for pretreating a carbon enhancer and applying it to laser treated skin.

Various treatments using laser or light have been used for skin regeneration. Among them, the 1,064-nm Nd: YAG laser treatment results in the improvement of skin tissue and wrinkles by increasing the homogenization of collagen by passing the heat damage induced by laser energy through the dermis (Bio Optics, Chonnam National University Press , 2008.01.20, Heungsung Bang, Lee, Jong Il, p132).

In the skin, snail proteins are expressed during the emergence of the hair follicles, where rapidly growing keratinocytes penetrate into the dermis beneath the skin. Growth of keratinocytes mediated by snail proteins is initiated by activated γδ T cells, which play an important role in wound healing. γδ T cells are known to continuously express FGF (fibroblast growth factor) -9 mRNA and synthesize FGF9 protein. FGF9 is expressed in both mesothelial and epithelial cells and is secreted from these cells and is known to affect skeletal development, bone regeneration and lung development.

 On the other hand, studies on the skin of FGF have been inadequate, and epidermal growth factor and basic fibroblast growth factor have been commercialized and used for cosmetics in order to promote wound healing and improve wrinkles.

Accordingly, the present inventors have made intensive efforts to induce the expression of FGF9 using a laser of a specific wavelength and confirm the effect of skin regeneration. As a result, it has been found that by increasing the expression of FGF9 by applying a carbon enhancer to the skin, The thickness of the outer skin and the dermis is increased, and the present invention is completed.

It is an object of the present invention to provide a cosmetic composition for skin regeneration comprising FGF (fibroblast growth factor) as an active ingredient for pretreating a carbon enhancer and applying it to laser treated skin.

The present invention provides a cosmetic composition for skin regeneration comprising FGF (fibroblast growth factor) as an active ingredient for pretreating a carbon enhancer and applying it to laser treated skin.

In another embodiment of the present invention, there is provided a pharmaceutical composition for skin regeneration comprising FGF (fibroblast growth factor) as an active ingredient for pretreating a carbon enhancer and applying it to laser treated skin.

In the present invention, the wavelength of the laser may be 800 to 1200 nm, or may be 10300 to 10900 nm. In the present invention, an increase in the expression of FGF9 was confirmed when a laser with a wavelength of 800 to 1200 nm or 10300 to 10900 nm was treated, and it was confirmed that the thickness of the dermis and the outer skin of the skin was increased accordingly. However, such effects can not be confirmed in other laser wavelength ranges.

In the present invention, the laser is a quasi-long pulsed Nd: YAG Method or a Q-switched Nd: YAG method.

Quasi-long pulsed Nd: YAG Method is characterized in that the laser irradiation time is longer than that of the Q-switched Nd: YAG method, so that the laser energy is transferred to the carbon powder rather than the effect of destroying the carbon powder to obtain the heat transfer effect. On the other hand, the laser treatment by the Q-switched Nd: YAG method is mainly responsible for destroying carbon particles rather than heat transfer because the irradiation time is short.

In the present invention, the composition may be characterized by increasing the thickness of the epidermis and the dermis. In addition, the FGF may be FGF9.

The cosmetic composition according to the present invention may be selected from the group consisting of lotion, milk, cream, gel, essence and pack cosmetic. The pharmaceutical composition according to the present invention may be in the form of a suspension, a powder, a granule, A sustained-release preparation, an injection, an ointment, and a capsule. In addition, the pharmaceutical composition may be characterized in that it is intended for humans.

According to the present invention, when the carbon enhancer was applied to the skin and treated with a laser of a specific wavelength, it was confirmed that the expression of FGF9 was increased, and thus it was increased not only to the dermis but also to the thickness of the skin. FGF9 is known to affect the growth of the dermis but it is not known whether it affects the growth of the envelope. Therefore, the present invention is characterized in that the expression of FGF9 is increased to the skin thickness as well as the dermis have.

Examples of the cosmetic according to the present invention include lotion, milky lotion, cream, gel, essence, and pack cosmetic. The cosmetic composition containing the effective amount of the composition of the present invention has a thickened outer skin and a dermis of the applied area, thereby promoting regeneration of the skin tissue.

The term skin regeneration, as used herein, refers collectively to an increase in skin moisturizing, skin elasticity enhancement, increase in skin thickness, improvement in skin wrinkles, alleviation of skin irritation, and recovery of skin damage

"Lotion" is a transparent liquid cosmetic which is generally applied to the skin surface to keep the skin clean and healthy. The basic function of the lotion is to supply moisture and moisturizing ingredients to the stratum corneum of the skin, and lotion has the function of softening the skin. The cosmetic lotion is made by dissolving and stabilizing a substance which is difficult to dissolve in water to make the appearance transparent, a transparent or semitransparent one using microemulsion or lipid nanospheres, an O / W type (water-in-oil type) Opaque lotion emulsified in W / O type or W / S type, and water-soluble polymer blended therein.

The lotion contains, for example, the following components besides the composition of the present invention. In other words, cosmetics such as ion-exchange water, ion-exchanged water and the like are used to dissolve water-soluble components and to supply moisture to the stratum corneum; alcohols such as ethanol, propanol and the like for dissolving, sterilizing and sterilizing oil- Emollients (oil components that prevent water from evaporating), polyoxyethylene oleyl alcohol ethers, etc., for improving the moisture retention and feeling of use, such as ester oils and vegetable oils, etc., A buffer for adjusting the pH of a product such as citric acid, lactic acid, and amino acids; a flavoring agent such as vanillin, orange flavor, lemon flavor, milky flavor geraniol, Preservatives for inhibiting microorganisms such as methylparaben, phenoxyethanol, etc. to prevent decay, coloring agents for coloring, metal ion sequestrants, ultraviolet rays Hand et al., Fading agent to prevent fading or discoloration; a drug, such as astringents and, fungicides, energetic agents, anti-inflammatory agents, or whitening agent, may contain a mixture of two or more. The composition of the present invention may contain 0.00 to 20% by weight, or 0.01 to 10% by weight, or 0.1 to 3% by weight, based on 100% by weight of the total amount of the lotion.

"Milky lotion" is an emulsion that has an intermediate property between lotion and cream, and generally has fluidity. Latex is a cosmetic used for supplying moisture, moisturizing agent, oil and the like to the skin, in order to maintain the moisturizing balance, moisturizing property and flexibility of the skin. The components contained in the emulsion are similar to those contained in the cream described later, but the emulsion has a fluidity, so the amount of solid oil or lead is smaller than that of the cream. The emulsion may contain, for example, from 1 to 20% by weight, or from 1 to 10% by weight, or from 1 to 5% by weight of the composition of the present invention.

"Cream" is a type of emulsion in which one of the liquids that do not mix with each other, such as water and oil, is dispersed in a stable state in the other dispersion medium. In the treatment method of the present invention, a known " cream " can be appropriately used depending on its use and the like. These creams include emolent creams to moisturize or soften the skin, massage creams to promote blood circulation, cleansing creams for skin cleansing, hair removers for hair removal, deodorant creams for deodorization, Exfoliated cream, and the like.

The cream contains, for example, the following ingredients. Examples of the water component contained in the cream include purified water such as ion-exchanged water, alcohols for dissolving and sterilizing oil-soluble components such as ethanol and propanol, glycerin, PEG, and hyaluronic acid for moisturizing the stratum corneum A moisturizer, and a mucus such as queen seed, pectin, and cellulose derivatives. Examples of the oil component contained in the cream include hydrocarbons such as squalene, liquid paraffin, petrolatum and solid paraffin; oils such as olive oil, almond oil, cacao fat, castor oil, etc., lead, lead, lanolin and jojoba oil; And higher alcohols such as cetanol and stearyl alcohol; esters such as IPM, glycerin triester and pentaerythritol tetraester; and silicone oils such as polysiloxanes. The amount of each component contained in the cream varies greatly depending on the type and use thereof, but known ones may be appropriately used. The cream may contain 1 to 100% by weight, or 1 to 20% by weight, 1 to 10% by weight, or 5 to 10% by weight of the composition of the present invention.

The gel is a cosmetic which is uniform in the appearance state such as a gel or a sol and is transparent to translucent. A water-based gel for supplying moisture to the skin and moisturizing the skin, an oil-based gel for maintaining moisturization of the skin and supplying oil, a water-based gel for massage, and a cleansing gel. The gelo may be prepared by using a gelling agent containing a water-soluble polymer such as carboxyvinyl polymer or methylcellulose. In addition, a gel-like massage oil may be used.

Essence is basically a component such as the above-mentioned lotion, emulsion and cream, and includes those containing an emulsion, a solubilizing agent, a moisturizer, water and other medicines. Known cosmetic liquids in the treatment method of the present invention can be used. Examples of the emulsion contained in the serum include natural vegetable oils such as olive oil, camellia oil, sesame oil, sunflower oil, sweet almond oil and jojoba oil; diglycerin esters or triglycerin esters of fatty acids such as capric acid, myristic acid, oleic acid, isostearic acid, And the like. These emulsions mainly function as emollients. Examples of the solubilizing agent in the serum include propylene glycol fatty acid esters such as glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters and propylene mono-stearic acid glycols, glycerin, diglycerin, ethylene glycol, propylene glycol, And polyhydric alcohols such as phenol and phenol. On the other hand, the solubilizing agent is preferable because it uses glycerin or diglycerin and improves the heat effect in massaging. Examples of the water contained in the serum include distilled water and deionized water. Other medicines include bactericides, preservatives, vitamins, natural extracts from plants, coloring matters, perfumes, and the like.

The amount of each component constituting the serum may be a known component amount. For example, when the total amount of the serum is 100 wt%, the composition of the present invention may be contained in an amount of 1 to 20 wt%, 1 to 10 wt%, or 1 to 5 wt%. Also, water may be used in an amount of about 65 to 90% by weight of an oil, 1 to 10% by weight of a solubilizing agent, 1 to 30% by weight of a moisturizer, and 0 to 10% by weight of other medicines. The serum may be prepared according to a known production method.

The "pack cosmetic" is applied to the target site for the purpose of moisturizing the skin, promoting blood circulation, and cleansing the skin. The pack cosmetics generally include jellies, pastes, powders, and cream-like liquids. They are applied to the face to form a film, followed by peeling, wiping after application, and washing after application . When powder is used, it is used to dissolve uniformly in water or in suspension. Pack cosmetics in which a cosmetic material is impregnated into a nonwoven fabric or collagen sheet having a shape such as an eye mask or pack cosmetics in which the above nonwoven fabric is immersed in a cosmetic composition when used.

Pack cosmetics may contain about 1 to 20% by weight, or 1 to 10% by weight, or 1 to 5% by weight, and most preferably about 2 to 3% by weight of the composition of the present invention. The other composition may be a known composition used for pack cosmetics, and may be prepared according to a known production method.

However, without being limited to the above description, each of the above cosmetic compositions can be used according to a method commonly used.

When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc., in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995). The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, the composition can be administered by intravenous infusion, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration, mucosal administration, and topical administration.

The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on such factors as formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, route of administration, excretion rate, . The dosage of the pharmaceutical composition of the present invention may be 0.001-100 mg / kg (body weight), 0.01-80 mg / kg (body weight), and 0.1-60 mg / kg (body weight) per day on an adult basis. In addition, depending on the judgment of a doctor or a pharmacist, it may be administered once or several times a day at intervals of a certain time.

According to the present invention, when the carbon enhancer is applied to the skin and treated with a laser of a specific wavelength, the degree of expression of FGF9 is increased, and the thickness of the dermis and the skin becomes thick, which is effective for skin regeneration.

FIG. 1 shows the result of hematoxylin-eosin staining after pretreatment of the skin with a carbon enhancer and laser treatment (FIG. 1). (B) Carbon enhancer Pretreatment and 1,064-nm quasi-long pulsed Nd: YAG laser treatment).
FIG. 2 shows changes in the thickness of the skin and the dermis after the carbon enhancer pretreatment and laser treatment on the skin (a) 1,064-nm quasi-long pulsed Nd: Nd: YAG laser).
Figure 3 shows changes in the thickness of the epidermis and dermis after treatment of the skin with 10,600 nm of laser.
FIG. 4 shows the results of (a) treatment with 1,064-nm quasi-long pulsed Nd: YAG laser, (b) treatment with 1,064-nm quasi-long pulsed Nd: YAG laser, nm Q switched Nd: YAG laser).
FIG. 5 shows the increase in expression of FGF9 after treating the skin with a laser at 10,600 nm.

Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited by the following examples.

Carbon enhancer and laser treatment on mouse skin

In order to carry out the present invention, a 7-week-old hairless mouse (Hr-1; Japan SLC Inc., Shizuoka Ken, Japan) was used. Topical EMLA cream (AstraZeneca AB, Sweden) was applied for local anesthesia before laser treatment of the mice, and topical carbon cream was applied to the right side of the mouse for 3 minutes.

The mice were divided into two groups and the first group was injected with a 1.464 kDa fluorescence quasi-long pulsed Nd: YAG laser (Spectra VRMIII ^TM , Korea) of 300 μsec quasi-long pulse Laser energy was transferred to both sides of the mouse at a repetition rate of 10 Hz. For the second group, the laser energy was transferred at a repetition rate of 10 Hz to both sides of the mouse using a 1.6 J / cm 2 fluence, a Q-switched Nd: TAG laser (Spectra VRMIII ^TM , Respectively. The third group was treated with a laser with a wavelength of 10,600 nm.

Histological analysis of mouse skin

Skin samples were obtained after 1 (6 hours), 3, 5, 7, 10, 14, and 21 days after laser treatment of the mice, fixed in 10% formalin and placed in paraffin, 5 μm) and placed on a microscope slide. The slides were re-paraffinized with xylene and then rehydrated with diluted ethanol. It was then used for hematoxylin-eosin staining and immunohistochemistry. The activity of endogenous peroxidase was controlled with 0.3% hydrogen peroxide-methanol for 20 minutes at room temperature and the antigen was washed out for 2 minutes with antigen collection buffer (DAKO, USA) and pressurization . Sections were incubated for 2 hours with a Levitt polyclonal anti-mouse FGF9 antibody (Abcam, UK) diluted 1/100 and a mouse monoclonal anti-human snail antibody diluted 1/100 (Cell Signaling, USA). The slides were washed with 1% PBS containing Tween-20 (PBST) and incubated for 30 min at room temperature with a secondary antibody (Real ™ Envision ™ HRP Rabbit / Mouse, USA).

2-1: 1,064-nm quasi-long pulsed Nd: YAG laser treated

When the 1,064-nm quasi-long pulsed Nd: YAG laser was applied to the skin without application of the carbon enhancer, no significant change in the skin thickness was observed after 1, 3, and 5 days, Was observed. After 14 and 21 days, no major changes were observed again. Also, a large increase in dermal thickness occurred at 3 or 5 days. On the other hand, when the carbon enhancer was applied to the skin and then treated with 1,064-nm quasi-long pulsed Nd: YAG laser, a large increase in shell thickness was observed after 6 hours, and 3, 5, 7, 10, 14 and 21 The thickness of the envelope also increased significantly after one day. In addition, a large increase in dermal thickness was observed after 3, 5, 10, 14, and 21 days (Figs. 1 and 2A).

As a result, sporadic keratinocytes were observed 1, 3 days after treatment with 1,064-nm quasi-long pulsed Nd: YAG laser after carbon enhancer application. On the other hand, when the laser was treated without applying the carbon enhancer, no change in keratinocyte cell death was observed. In addition, clinically, the parakeratotic stratum corneum, which appears after laser treatment scaling, disappears naturally on the third day after treatment in the laser-treated mice treated with the carbon enhancer, whereas only the laser treatment without the carbon enhancer In one case, such a phenomenon did not appear.

2-2: With 1,064-nm Q-switched Nd: YAG laser treatment

When the 1064-nm Q-switched Nd: YAG laser was applied to the skin without application of the carbon enhancer, no significant change was observed in the skin thickness after 1 or 3 days, A large increase in thickness was observed. No significant changes were observed again after 21 days. Also, a large increase in dermal thickness occurred at 5 days. On the other hand, in the case of treatment with 1,064-nm Q-switched Nd: YAG laser after applying the carbon enhancer to the skin, no significant change was observed in the skin thickness after 1 or 3 days, and 5, 7, 10 or 14 days A large increase in shell thickness was observed at the time of elapse. No significant changes were observed again after 21 days. A large increase in dermal thickness was also observed after 3, 5, 7, 10, 14, and 21 days (Fig. 2B).

As a result, no changes in cell killing or mitotic characteristics were observed in the case of treatment with a 1,064-nm Q-switched Nd: YAG laser without or with a carbon enhancer.

2-3: with 10,600-nm laser treatment

When the skin was treated with 10,600 nm laser, there was no significant change in skin thickness after 1 day, and a large change was observed after 3, 5, 7, and 10 days. On the other hand, a large increase was observed in the dermal thickness after 14 days and 21 days (Fig. 3).

Observation of increased expression of FGF9

3-1: 1,064-nm quasi-long pulsed Nd: YAG laser treated

FGF9 expression was observed only in small areas of the epidermis after 5, 7, and 21 days of treatment with 1,064-nm quasi-long pulsed Nd: YAG laser without application of the carbon enhancer to the skin. 7, 10, 21 days after transplantation. On the other hand, when the skin was treated with a carbon enhancer and treated with a laser, an increase in FGF9 was observed only at a small area of the outer skin after 1, 3, 5, 7, 14 and 21 days, After 5, 7, and 21 days, an increase in expression of FGF9 was observed (Fig. 3a).

3-2: Treatment with 1,064-nm Q-switched Nd: YAG laser

When the 1064-nm Q-switched Nd: YAG laser was applied to the skin without the application of the carbon enhancer, the expression of FGF9 was observed only at a small area of the skin after 1, 3, 5, 7 and 10 days, After 1, 3, 5, 7, 10, and 21 days, overexpression of FGF9 was observed. On the other hand, when the skin was treated with a laser after the carbon enhancer was applied, the expression of FGF9 was slightly increased after 3 days in the outer coat, and in the dermis, the expression of FGF9 was significantly increased after 5, 7, (Fig. 3B).

3-3: With 10,600-nm laser treatment

When the skin was treated with a laser of 10,600 nm, overexpression of FGF9 was observed after 3. 5 and 7 days, and FGF9 was overexpressed again after 21 days (FIG. 5).

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

Claims (17)

(Fibroblast growth factor-9) for pretreatment of the carbon enhancer and applied to the laser treated skin as an active ingredient,
Wherein the wavelength of the laser treatment is 10,300 to 10,900 nm.
delete delete delete The method according to claim 1,
Wherein the laser is processed by a Q-switched Nd: YAG method.
The method according to claim 1,
Wherein the composition increases the thickness of the outer skin and the dermis.
delete The method according to claim 1,
Wherein the composition is selected from the group consisting of lotion, milky lotion, cream, gel, essence and pack cosmetic.
(Fibroblast growth factor-9) for pretreatment of the carbon enhancer and applied to the laser treated skin as an active ingredient,
Wherein the wavelength of the laser treatment is 10,300 to 10,900 nm.
delete delete delete 10. The method of claim 9,
Wherein the laser is processed by a Q-switched Nd: YAG method.
10. The method of claim 9,
Wherein the composition increases the thickness of the outer skin and the dermis.
delete 10. The method of claim 9,
Wherein the composition is selected from the group consisting of suspensions, powders, powders, granules, tablets, sustained release preparations, injections, ointments and capsules.
10. The method of claim 9,
The composition for skin regeneration is characterized in that the composition is intended for human.

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