KR20070000005A - Cosmetic composition containing fibroblast growth factor - Google Patents

Abstract

The present invention relates to a functional cosmetic composition for wrinkle improvement and / or anti-aging containing fibroblast growth factor, specifically the present invention contains a fibroblast growth factor to significantly improve the aging phenomenon, such as wrinkles of the skin, the fibroblast The present invention relates to a cosmetic composition in which growth factors are separated from allogeneic or self-derived adipocytes, thereby securing safety and stabilizing with hydrophilic polymers to improve the problem of lowering titer.

Description

Cosmetic composition containing fibroblast growth factor {Cosmetic composition containing fibroblast growth factor}

The present invention relates to a functional cosmetic composition for wrinkle improvement and / or anti-aging containing fibroblast growth factor.

More specifically, the present invention contains a fibroblast growth factor to significantly improve the aging phenomenon, such as wrinkles of the skin, and the fibroblast growth factor is separated from allogeneic or self-derived adipocytes to ensure safety and hydrophilic polymer The present invention relates to a cosmetic composition in which the problem of lowering of titer is improved by stabilizing and using.

Skin aging is divided into two types. One is the aging phenomenon caused by the increase of age due to internal aging and the other is the aging phenomenon caused by the external environment such as ultraviolet rays or pollution due to the external aging.

Many theories have been suggested so far about skin aging, but the most scientific approach to skin aging is skin aging by oxidation. Human skin is composed of epidermis, dermis and connective tissue including stratum corneum, of which stratum corneum is composed of dead cell layer formed through differentiation process of keratinocyte, basal cell of epidermis, and affects human body by external environment. It has a role to protect against. In addition, the dermis layer inside the skin is composed of collagen and elastin, known as elastic fibers, to play a role in protecting the skin from sagging by giving it elasticity.

The theory of antioxidant is that the elastic fibers such as collagen and elastin are damaged by free radicals produced by factors such as external ultraviolet rays, thereby reducing the elasticity of the skin, thereby creating wrinkles. Until now, it has been used substances such as retinol or plant extracts to prevent the aging of the skin, especially wrinkles. However, these substances have low side effects or cause skin irritation, redness and inflammation, which have serious disadvantages for the skin.

In addition, based on recent advances in biochemistry and molecular biology, we have discovered a small amount of signal substances (growth factors) in our living bodies, and the aging theory of living organisms is being redefined based on this (Stanley Corhen, Nobel Lecture 1986). , Dec, 8). In addition, this signal substance (growth factor) decreases in vivo as age increases, and it is revealed that this growth factor is closely related to our aging (Handbook of Experimental Pharmacology, Vol. 95/1). , 1990 Richard E. Fitzpatrick.

Therefore, this researcher is trying to find skin anti-aging material, especially skin wrinkle improvement material, and the fibroblast growth factor, which has not been applied as a cosmetic until now, meets this purpose. It has been found that it can be effectively used as a component.

However, fibroblast growth factor is a kind of protein component that is difficult to grasp the structure, and has a lot of limitations and problems to apply to cosmetics because the stability is very poor in the general environment. In other words, because it is generated in vivo and acts on the cells as needed, there is no storage problem, but for use in cosmetics, the activity is lost by compatibility with other bases and other ingredients.

In particular, the fibroblast growth factor is very expensive, it was judged that it is impossible to apply it as a cosmetic composition without guaranteeing its stability.

In order to solve this problem, the prior art has been investigated, but in the case of fibroblast growth factor, there is almost no research on how to ensure its stability. However, as a method of stabilizing existing proteins, Korean Patent No. 315908 describes a method of stabilizing using calcium phosphate buffer, and Korean Patent Publication No. 10-2000-0023751 discloses a technique using a polyoxyethylene copolymer. It was just.

However, both of these methods are not suitable for stabilizing proteins in cosmetics.

The lack of research on the stabilization of fibroblast growth factor is such that the structure of the fibroblast growth factor has not been confirmed, and it has a structural disadvantage that can be easily transferred to other forms in structure, and also it is not easy to stabilize the protein. Because.

Therefore, this researcher has been studying for many years to apply the fibroblast growth factor to the skin in a stable state. As a result, the fibroblast growth factor can be stabilized using water-soluble polymer resin.

It is an object of the present invention to provide a cosmetic composition having safety and stability and improved skin anti-aging effect.

In order to achieve the above object, the present invention provides a functional cosmetic composition containing a fibroblast growth factor.

The present invention also provides a functional cosmetic composition containing allogeneic or self-derived adipocytes and / or fibroblast growth factors isolated therefrom.

The present invention also provides a cosmetic composition containing the fibroblast growth factor as an active ingredient and stabilized it with a water-soluble polymer resin.

Hereinafter, the present invention will be described in detail.

A first aspect of the present invention relates to a functional cosmetic composition containing a fibroblast growth factor.

Fibroblast growth factor (FGF) is a group of potent mitotic stimulators of heparin binding to both normal ventricular fibroblasts and established cell lines. (Godpodarowitz, D. et al. (1984), Proc., Natl., Acad., Sci. USA, pp. 81: 6983). FGF group includes acidic FGF (FGF-1), basic FGF (FGF-2), INT-2 (FGF-3), K-FGF / HST (FGF-4), FGF-5, FGF-6, KGF (FGF -7), AIGF (FGF-8) and FGF-9 to FGF-18. Every FGF has two cysteine residues as conservative residues and its amino acid sequence has 30-50% homology. These factors include normal peritoneal mesodermal-derived and neural toxin-derived cells, induced granulosa cells, adrenal cortex cells, crondocite, myoblasts, corneal and vascular endothelial cells (bovine or human), vascular smooth muscle cells, lens, retina and prostate Epithelial cells, oligodendrocytes, (glial glial) astrocytic cells, crondocytes, myoblasts and osteoblasts have mitotic promoting properties.

Fibroblast growth factor can also be promoted in a dissimilar fashion for many different cell types. These growth factors may promote cell migration to the wound (chemotactic chemotaxis), initiate new blood vessel formation (vasculature), revive and sustain nerves (neurotrophic), regulate endocrine function, express specific cellular proteins, and extracellular matrix Functions to promote or inhibit production and cell survival (Bayd, A. and Bolen, P., Handbook of Exp. Pharmacol. 95 (1): pp. 369-418 (1990)).

Thus, therapeutic approaches have been attempted to promote wound healing, neurotherapy, collateral vessel formation and the like using fibroblast growth factors. For example, fibroblast growth factor has been suggested as a way to minimize heart muscle damage in heart disease and cardiac surgery (US Pat. No. 4,378,437).

In view of the mitotic promoting effect as described above, the present invention uses a fibroblast growth factor in the cosmetic composition for wrinkle improvement and / or anti-aging.

The cosmetic composition containing the fibroblast growth factor according to the present invention has a protective effect against keratinocytes that cause skin wrinkles, and this effect is a component such as retinol, which has been previously used as an active ingredient of an anti-aging cosmetic composition. Compared with the improved effect.

Fibroblast growth factor used in the composition of the present invention can be purchased commercially, it can also be produced genetically by a known production method.

In addition, the cosmetic composition of the present invention can be used in addition to the above sunscreens, antioxidants, cell activation promoters, etc., which are known to be useful for preventing skin aging, and specifically used by adding retinol, vitamin C, alpha hydroxy acid, and the like. It is possible to do

A second aspect of the present invention provides a functional cosmetic composition containing allogeneic or autologous adipocytes and / or fibroblast growth factors isolated therefrom.

Specifically, fibroblast growth factors are known to be present in a significant amount in stem cells, and in particular, since a significant amount of such stem cells are present in adipocytes, the functional cosmetic composition is provided using such adipocyte derived stem cells.

In particular, there is an advantage that safety is secured by applying to the allogeneic or porcelain skin using stem cells isolated from allogeneic or autologous adipocytes and / or fibroblast growth factor separated therefrom as a cosmetic.

In addition, in terms of function, allogeneic or self-derived cells or hormones are used, so the skin is excellent in compatibility, and thus, an increased effect on skin wrinkle improvement can be obtained.

The third aspect of the present invention provides a cosmetic composition containing a fibroblast growth factor as an active ingredient and stabilized it with a water-soluble polymer resin or a polyhydric alcohol including two or more hydroxy groups in the monomer.

The present invention relates to a cosmetic composition using a fibroblast growth factor for the purpose of inhibiting skin aging, and is completed by stabilizing the fibroblast growth factor with a polymer resin or a polyhydric alcohol.

Specifically, in order to select a polymer resin suitable for the cosmetic composition according to the present invention, the present inventors attempted a method of stabilizing fibroblast growth factor with a variety of polymer resins, and as a result, the fibroblast growth factor is stabilized only in a polymer resin of a specific structure I found that.

That is, a method of protecting fibroblast growth factor using a polymer resin having a very high hydrophilicity was selected. This is because the hydroxy group present in the fibroblast growth factor forms a hydrogen bond with the hydroxy group of the hydrophilic polymer resin in order to suppress the reaction of the fibroblast growth factor with other components present in the cosmetic product. This is to minimize the growth of fibroblast growth factors to other substances by dissolving other oxygen.

In addition, it is possible to stabilize the fibroblast growth factor by selecting two or more hydroxyl groups among the polyhydric alcohols.

Specifically, the fibroblast growth factor is dissolved in polyhydric alcohol and then hydrated to saturate the hydrogen bond in the hydroxy group using a water-soluble polymer resin. As a result, the fibroblast growth factor may be protected from the outside air.

In addition, the hydroxy group of the polyhydric alcohol may cause hydrogenation around the remaining fibroblast growth factor, thereby blocking external oxygen.

In addition, sunscreens may be added to block the ultraviolet light that deactivates the protein.

The pH of the cosmetic composition according to the present invention is preferably maintained at 6 to 9, because when the pH falls below 5, there is a problem that the stability of the fibroblast growth factor is sharply lowered.

In this state, it can also be dispersed in the emulsion, gel or water phase components to maintain the existing pH and ingredient composition to prevent the transition to other materials.

The cosmetic composition according to the present invention preferably contains 0.000000001 to 0.001% (w / v) of fibroblast growth factor as an active ingredient, and particularly preferably contains 0.00000001 to 0.0001% (w / v).

If the content is less than 0.000000001%, the desired effect cannot be achieved. If the content is more than 0.0001%, the concentration of the product at a concentration higher than necessary will place a heavy burden on the price of the product.

The hydrophilic polymer resin used to protect the fibroblast growth factor from external substances is preferably contained 0.01% to 30% (W / V), particularly preferably 0.1% to 15% (W / V). As a kind of water-soluble polymer resin, it is preferable to use an acrylate copolymer, an allyl methacryl copolymer, an alkyl acrylate copolymer, etc. as a water-soluble high molecular substance with two or more hydroxyl groups in a monomer.

The content of the polyhydric alcohol is preferably contained 0.01% to 30% (W / V), particularly preferably 0.1 to 20%. Its kind includes a solution substance having two or more hydroxy groups, and includes glycerol, butylene glycol, propylene glycol, polyoxyethylene, and the like.

The sunscreen preferably contains 0.01% to 15% (W / V), particularly preferably 0.1 to 8%. Here, the UV-blocking component has a resonance structure and has an absorption spectrum of 280 nm to 400 nm. It is a mixture of dioxybenzone, lowson and dihydroxyacetone, methylanthranilate, benzophenone-4, octyl salicylate, and triethanol. Amine salicylate, synoxate, oxybenzone, octocrylene, digaloyl trioleate, paradimethylmethyl benzoate amyl, diethanolamine paramethoxycinnamate, octylmethoxycinnamate, paraaminobenzoic acid, glyceryl pava, Ethyldihydroxypropylpava, octyldimethylpaba, 2-phenylbenzimidazole-5-sulfonic acid, homosalate, dromethazole, butylmethoxydibenzoylmethane, octyltrizone, 3- (4-methylbenzyl Leeden) -campa and the like.

The prepared fibroblast factor and the polymer dispersion solution should be maintained at a pH of 6-9, and sodium citrate is used as the buffer material.

In addition, containing a small amount of antioxidant may help to improve stability, preferably containing 0.01 to 10% (W / V) of hypotaurine, particularly 0.1 to 5%.

Also preferred as a formulation of the composition of the cosmetic composition according to the present invention may be mentioned nutrition cream, massage cream, essence, pack and the like.

The cosmetics containing the fibroblast growth factor described above can be usefully used for the purpose of alleviating skin aging by comparing the fibroblast growth factor that does not stabilize and evaluate the stability against temperature and ultraviolet rays, as described in detail in the following experimental example. Was evaluated.

If the present invention will be described in more detail based on the Examples as follows, the present invention is not limited by the Examples.

<Manufacture example 1>

The formulation of the cosmetic composition containing the fibroblast growth factor (F4537, Sigma Aldrich) is shown in Table 1.

Composition ratio of cosmetics containing fibroblast growth factor Compounding ingredients (% by weight) Example 1 Example 2 Comparative Example 1 Comparative Example 2 end FGF 0.0000001 0.0000001 0.0000001 - Acrylate Copolymer 2.00 - 10.00 - glycerin 20.00 - 20.00 - Retinol - - - 0.10 Sunscreen 0.50 - 0.50 - Hippotaurine 0.10 - 0.10 - Sodium citrate 0.30 - 0.30 - I Butylene glycol 7.00 7.00 7.00 7.00 Cetanol 1.00 1.00 1.00 1.00 Octyldodecanol 7.00 7.00 7.00 7.00 Glyceryl Stearate 0.70 0.70 0.70 0.70 Solbitan Sesquioleate 0.50 0.50 0.50 0.50 Carboxy Polymer 0.30 0.30 0.30 0.30 Triethanolamine 0.30 0.30 0.30 0.30 antiseptic Quantity Quantity Quantity Quantity Medicine Quantity Quantity Quantity Quantity Pigment Quantity Quantity Quantity Quantity Purified water Remaining amount Remaining amount Remaining amount Remaining amount system 100.00 100.00 100.00 100.00

(A) The polyhydric alcohol, fibroblast growth factor, sunscreen, and sodium citrate are mixed and dissolved. After complete dissolution, hydrophilic polymer resin is mixed to adsorb fibroblast growth factor and sunscreen and antioxidant are added. It is completed by mixing the fibroblast growth factor hydrated with hydrophilic polymer resin on the other (b) phase.

Experimental Example 1

According to the preparation example, the cosmetics having the component ratios of Table 1 were prepared and stored at room temperature for 25 weeks and 45 ° C. for 4 weeks, and stored for 2 weeks and 4 weeks in ultraviolet light conditions to analyze the contents of fibroblast growth factors.

The analysis results are shown in Table 2.

Changes over time in Cosmetics Containing Fibroblast Growth Factor Content of FGF (%) Example 1 Example 2 Comparative Example 1 Right after manufacturing 99 101 99 25 ℃ after 2 weeks 98 99 68 45 ℃ after 2 weeks 91 96 36 45 ℃ after 4 weeks 93 93 21 UV 25 ℃ 95 97 27 UV 45 ℃ 91 94 17

As a result of measuring the change over time, in Examples 1 and 2 in which the fibroblast growth factor was hydrated by adsorbing the hydrophilic polymer resin, the fibroblast growth factor was prevented from coming into contact with external oxygen. It shows the difference.

Experimental Example 2

The protective effect of keratinocytes against the ultraviolet rays of fibroblast growth factor was tested by the following method.

Keratinocytes were dispensed into 96-well plates at the appropriate cell concentration, administered under optimal culture conditions, and stabilized for 4 hours to ensure sufficient dispersion of raw materials. After sufficiently dispersing the raw material, ultraviolet rays were irradiated for 8 minutes with a 40W double lamp in a sterile laboratory. After 24 hours, the survival rate of the cells was determined by comparing the negative control group irradiated for 8 minutes without treatment.

As shown in Table 3 below, 67% of the cell group treated with fibroblast growth factor, 54% of the cell group treated with retinol, and 55% of the negative control group. This suggests that fibroblast growth factor is higher in UV protection, while retinol is less effective in UV protection.

Results of Aging Relaxation Effect Defense effect Example 2 67% Comparative Example 2 54% Negative Control 55%

Experimental Example 3

In order to evaluate the activity of stabilized fibroblast growth factor added to the emulsion, the product was stored in Example 2 and Comparative Example 1 at 45 ° C. for 4 weeks to verify the effect of aging relaxation. The following experiment was performed using 30 hair loss mice each.

Irradiation of 2Mj / cm 3 at the back of the bald head using an UV irradiator at a frequency of 2 Mj / cm 3 was performed twice a week for 4 weeks to cause abnormal hyperkeratosis of the skin. Thereafter, the cosmetic composition of Example 2 containing the fibroblast growth factor stably was applied to one side of the back of the hair loss rat twice a day for 2 weeks, while the other side stabilized the fibroblast growth factor for comparison. Cosmetic Comparative Example 1 not applied. Two weeks later, the effect of aging was visually observed and evaluated (Jin Ho Chung et al. Archives of Dermatology aug 2001, 137,8). The results are shown in Table 4.

Results of Aging Relaxation Effect A noticeable effect Mitigating effect no effect Example 2 23 7 0 Comparative Example 1 4 8 18

In the case of applying the cosmetic composition of Example 2 which stabilized the fibroblast growth factor to artificially induced hair loss, it was observed that all 30 animals exhibited an alleviation effect of abnormal skin hyperkeratosis, which is a fibroblast growth factor. In view of the fact that cosmetics that do not stabilize stabilized in most cases do not show a mitigating effect is a significant result.

Experimental Example 4

In order to verify the antiwrinkle effect of stabilized fibroblast growth factor for women aged 30 to 40 years, 20 subjects were selected from each experimental group.

After storing the cosmetic product of Example 2 and the cosmetic composition of Comparative Example 1 with stabilized fibroblast growth factor for 4 weeks at 45 ° C., the product of Example 2 was applied around the right eye of the woman for 4 weeks twice a day. Comparative Example 1 was applied around the other eye for comparison. After 4 weeks, the wrinkle relief effect was visually observed and the results were summarized as follows.

Wrinkle Relaxation Effect A noticeable effect Mitigating effect no effect Example 2 8 12 0 Comparative Example 1 2 4 14

As can be seen from the results of Table 5, when applying the cosmetics stabilized fibroblast growth factor, all 20 women showed at least some alleviating effect, especially in 8 people showed a significant mitigating effect such as fibroblast growth factor It showed a significant improvement in wrinkles compared to unstabilized cosmetics.

Therefore, it was proved that the cosmetics stabilized fibroblast growth factor was superior to the cosmetics formulated without stabilization.

In addition, as a result of checking the cross-sectional view of the skin before and after applying the cosmetic composition of Example 2 for 4 weeks, it was confirmed that many deep wrinkles disappeared (see FIGS. 1 and 2).

As described above, by stabilizing the fibroblast growth factor using a hydrophilic polymer resin it was possible to improve the safety problem in the existing cosmetic applications and to continue the activity of the product for a long time. Therefore, the cosmetic composition of the present invention is expected to be useful for this specific purpose.

Figure 1 shows the wrinkle improvement activity through the skin cross-sectional graph after applying a cosmetic formulated with a stabilized fibroblast growth factor according to the present invention on the skin of female subjects.

FIG. 2 is a cross-sectional graph of skin of a female subject different from the subject of FIG. 1.

A: Before applying cosmetics B: After applying for 4 weeks

Claims (27)

Wrinkle improvement and / or anti-aging functional cosmetic composition containing fibroblast growth factor. The cosmetic composition according to claim 1, which contains 0.00000001 to 0.001% (w / v) of fibroblast growth factor. The composition according to claim 2, which contains from 0.00000001 to 0.0001% (w / v) of fibroblast growth factor. The composition of claim 1, wherein the fibroblast growth factor is one or more selected from chemically synthesized, DNA recombinant methods, or isolated from living organisms. The composition of claim 4 wherein the fibroblast growth factor is isolated from allogeneic and / or autologous adipocytes. The composition of claim 5, wherein the fibroblast growth factor is isolated from adipocyte derived stem cells (ACDS). The composition of claim 1, further comprising at least one component selected from the group consisting of a hydrophilic polymer resin, a polyhydric alcohol, and a sunscreen agent. The composition of claim 7, wherein the hydrophilic polymer resin is contained in an amount of 0.01 to 30% (w / v). The composition of claim 8, wherein the hydrophilic polymer resin is contained in an amount of 0.1 to 15% (w / v). The cosmetic composition according to claim 7, wherein the hydrophilic polymer resin is a polymer resin having two or more hydroxy groups in the monomer. The composition of claim 10, wherein the hydrophilic polymer resin is at least one material selected from the group consisting of acrylate copolymers, allyl acrylate copolymers, and alkyl acrylate copolymers and has a molecular weight of 1,000 to 1,000,000. 8. The composition of claim 7, wherein the polyhydric alcohol is contained in an amount of 0.01 to 30% (w / v). The composition according to claim 12, wherein the polyhydric alcohol is contained in 0.1 to 20% (w / v). The composition according to claim 7 or 12, wherein the polyhydric alcohol is a substance having two or more hydroxy groups. 15. The composition of claim 14, wherein the polyhydric alcohol is selected from the group consisting of glycerol, butylene glycol, propylene glycol, polyoxyethylene and mixtures thereof. 8. The composition of claim 7, wherein the sunscreen is contained in an amount of 0.01 to 15% (w / v). 17. The composition of claim 16, wherein the sunscreen agent is present at 0.1% to 10% (w / v). The composition of claim 7 or 16, wherein the sunscreen is a material having a resonance structure and having an absorption spectrum of 280 nm to 400 nm. 19. The sunscreen according to claim 18, wherein the sunscreen is selected from dioxybenzone, a mixture of lowson and dihydroxyacetone, methylanthranilate, benzophenone-4, octylsalicylate, triethanolamine salicylate, synoxate, oxybenzone, Octocrylene, digaloyl trioleate, para-dimethylbenzoic acid amyl, diethanolamine paramethoxycinnamate, octylmethoxycinnamate, paraaminobenzoic acid, glyceryl paba, ethyldihydroxypropyl pava, octyldimethylpaba , The group consisting of 2-phenylbenzimidazole-5-sulfonic acid, homosalate, dromethazole, butylmethoxydibenzoylmethane, octyltrizone, 3- (4-methylbenzylidene) -campa and mixtures thereof Composition selected from. The cosmetic composition according to claim 1, wherein the pH is maintained in the range of 6 to 9, 21. The composition of claim 20 comprising sodium citrate buffer solution. The composition of claim 1 further comprising an antioxidant. 23. The composition of claim 22, wherein the composition contains 0.01 to 10% (w / v) of hypotaurine as an antioxidant. Wrinkle improvement and / or anti-aging functional cosmetics comprising the ingredients of claim 1 formulated in the form of nutrition cream, massage cream, essence or pack. Cosmetic composition containing allogeneic and / or self-derived adipocytes. A cosmetic composition according to claim 25 containing stem cells isolated from allogeneic and / or autologous adipocytes. The cosmetic composition according to claim 25 or 26, which contains fibroblast growth factor obtained from adipocytes or stem cells.