KR100604068B1 - Cosmetic compositions - Google Patents

Abstract

The present invention relates to a cosmetic composition for the purpose of preventing or improving wrinkles and skin aging, which comprises a polyethoxylated vitamin C derivative as a free radical scavenger or antioxidant.

The polyethoxylated vitamin C derivatives of the present invention exhibit relatively high solubility in both water and organic solvents, have high stability and excellent skin absorption, and have excellent anti-oxidation or radical scavenging functions. There is a useful effect in preventing or improving wrinkles and skin aging.

Free radical scavengers, antioxidants, polyethoxylated, vitamin C derivatives, wrinkles, skin aging

Description

Composition containing polyethoxylated vitamin seed derivatives as free radical scavengers or antioxidants

The present invention relates to a cosmetic composition containing a polyethoxylated vitamin C derivative as a free radical scavenger or antioxidant. More specifically, the present invention provides the following general formulas (I) and (II), wherein PEG is (CH ₂ CH ₂ O) nOR ₁ and means an integer of n = 2-200, and R ₁ is C1-. C6 lower alkyl group], the present invention relates to a cosmetic composition containing a polyethoxylated vitamin C derivative useful for preventing or ameliorating wrinkles and skin aging.

In general, there are many theories explaining skin aging, but among them, the free radical theory that the skin ages by free radicals caused by various factors in and out of the body is accepted as the most valid theory. Free radicals are chemically highly reactive chemicals that occur when the skin is irradiated with UV light or during the respiration of cells in the skin. Most of the free radicals related to aging of the skin are Reactive Oxygen Species (ROS), which include super oxide radical, hydrogen peroxide (H ₂ O ₂ ), and hydroxy radical ( Hydroxy radicals, Singlet oxygen and the like. These reactive oxygen species are generated during ultraviolet irradiation or respiration, causing multi-step chain reactions to cause peroxidation of lipids, which are components of cell membranes. Lipid peroxidation generates various active species such as radicals, peroxides, aldehydes, and epoxides, and damages DNA, RNA, proteins, cell membranes, and cellular structures. Toxicity of these reactive oxygen species is considered to be a major cause of cancer, tissue damage, and aging (Black HS, Photochem photobiol. 46 (2), 213, 1987). The peroxidation of the membrane lipids that make up the cell changes the structure and fluidity of the cell membrane, increases the permeability of cellular material, leaks of lysosome enzymes, inactivation of membrane enzymes and transport proteins, and covalent crosslinking of lipids and proteins. It leads to production, protein chain cleavage, DNA damage and mutations. Among these reactions, peroxidation of skin cell membranes and modification of dermal proteins are known to be most closely associated with skin aging. Aerobic organisms have protective mechanisms to prevent the formation of these oxidants and lipid peroxidation. These protective mechanisms include enzymes such as superoxide dismutase and catalase, α-tocopherol (vitamin E), β-carotene, and ascorbic acid (ascorbic acid). acid, Vitamin C) and glutathione

Fat soluble and water soluble antioxidants or radical scavengers such as glutathione. Since these free radicals or reactive oxygen species are so deeply related to skin aging, conventionally, by adding superoxide dismutase (SOD), vitamin-E derivatives, vitamin C and its derivatives, flavonoids and the like to cosmetics, Many efforts have been made to obtain skin anti-aging effects, but it is difficult to expect substantial effects due to poor stability and safety when formulated in cosmetics. In particular, vitamin C is a high-safety antioxidant, which enhances the synthesis of collagen as a cofactor of prolinehydroxylase (Quaglino, D. Jr., et Al., J. Biol. Chem. 1997, 272, 345.] was also attracting attention because of the effect of, but there is a difficulty in using a product that requires a long time due to low chemical stability. In particular, in the case of functional cosmetics for the purpose of preventing skin aging, in order for the agonist to act, it must pass through the stratum corneum of the skin and reach the cells in the epidermis, so transdermal absorption of the agonist is very important. Do. In general, the skin penetration rate of a substance is related to the lipophilicity of that substance. In case of substances similar to lipophilicity of skin, distribution coefficient to skin is known to be good for percutaneous absorption. Ascorbic acid is known to have high hydrophilicity, which makes it difficult to absorb percutaneously due to its low distribution to the skin.

The present invention has been made to solve the above problems, the present inventors have introduced a polyethoxyl as a core of the polyethylene glycol at the 2nd or 3rd position of ascorbic acid (vitamin C) which is the main cause of chemical instability The graded vitamin C derivative has the characteristics of polyethylene glycol, so it has relatively high solubility in water and organic solvents, and has high stability and skin absorption, and excellent antioxidant or radical scavenging function. Experiments have demonstrated its effectiveness to complete the present invention. It is therefore an object of the present invention to provide a composition containing the following general formulas (I) and (II) and containing polyethoxylated vitamin C derivatives useful for the prevention or improvement of wrinkles and skin aging.

Generally, the in vitro effect of ascorbic acid derivatives is lower than that of ascorbic acid. As shown in Table 1 and Table 2, the in vitro effect of the polyethoxylated ascorbic acid derivative is somewhat inferior to ascorbic acid, but when applied to the cosmetic composition, the percutaneous absorption and preservation stability is increased, The anti-wrinkle effect (in vivo) by UV rays was shown to be higher than that of ascorbic acid.

The present invention is to add a polyethoxylated vitamin C derivative to an external skin ointment or cosmetics, that is, softening longevity, nourishing longevity, nutrition cream, massage cream, lotion, essence, pack and the like.

Hereinafter, the present invention will be described in more detail in the general formulas (I) and (II) [wherein PEG is (CH ₂ CH ₂ O) nOR ₁ and means an integer of n = 2-200, and R ₁ is C1-C6 lower alkyl group] may vary depending on the formulation, but can be used in amounts ranging from 0.001% to 90% (W / W) based on dry weight. In general cosmetic formulations, preferably 0.01% -50% (W / W) is added to the aforementioned external skin ointments or cosmetics. It is difficult to expect substantial effects below this concentration, above that it will affect formulation and product stability.

The present invention is described in more detail through the following experiments and examples. However, the present invention is not limited to the following examples.

Experimental Example 1. Measurement of free radical scavenging ability

The free radical scavenging ability of the polyethoxylated vitamin C derivative was measured as follows. The method used was carried out by 1,1-Diphenyl-2-Pycryl-Hydrazyl (DPPH) method (Blois, MS Nature 181, 1190 (1958)). DPPH is a relatively stable free radical which, when present in the radical state, exhibits maximum absorption at 517 nm and loses its absorbance when erased. DPPH was used by Sigma Co., Ltd. and dissolved in methyl alcohol at a concentration of 0.15 mM. First, polyethoxylated vitamin C derivatives are prepared for each concentration (1 μg / ml-100 μg / ml) and 100 μl is added to each well of a 96 well plate. 100 μl each of DPPH solution was added thereto, and the mixture was left at room temperature for 30 minutes, and then the absorbance at 517 nm was measured using a Micro plate reader (BioTek EL-340). In this case, 100 μl of methyl alcohol was used instead of the polyethoxylated vitamin C derivative. The concentration of polyethoxylated vitamin C derivatives when the absorbance of the sample was half the absorbance of the control group was expressed as IC ₅₀ (Inhibitory Concentrati on ₅₀ ), and the results are shown in Table 1 below.

Free radical scavenging activity of polyethoxylated vitamin C derivatives (concentration: w / v) Ascorbic acid 3-PEG ₃₅₀ -Ascorbic Acid (I) 2-PEG ₃₅₀ -Ascorbic Acid (II) IC ₅₀ at 30 min 0.0005% 0.004% 0.003% IC ₅₀ at 60 min - 0.003% 0.003% IC ₅₀ at 17 hr - 0.0009% 0.0025%

As can be seen from the results, it can be seen that the polyethoxylated vitamin C derivative is a very powerful free radical scavenger and has excellent sustainability.

Experimental Example 2 Measurement of Inhibition of Intracellular Lipid Peroxidation by Free Radicals

Cells cultured with polyethoxylated vitamin C derivatives having excellent free radical scavenging ability and cultured as follows were tested for the inhibition of intracellular lipid peroxidation by free radicals generated by UV light. The cells used were hamster-derived fibroblast species called V79-4. Medium was used by adding 10% bovine serum to DMEM and incubated at 37 ℃, 5% CO ₂ conditions. The cells are inoculated at a concentration of 2 × 10 5 cells / dish in a 60 mm cell culture petridish and incubated for 3 days. In the culture, the polyethoxylated vitamin C derivative is added to the culture medium and cultured. After 3 days, pour out the medium, wash twice with PBS solution, add 1 ml of PBS to the culture vessel, and irradiate UV A (UVA) with a constant amount of light (15J / cm 2). Immediately after irradiation, the PBS solution is changed to a normal medium containing a polyethoxylated vitamin C derivative and further incubated for 24 hours.

Quantification of lipid peroxides produced in cells was performed using Thiobarbithuric acid (TBA) reactivity, and the experimental method was as follows (Kari. P et al, J. Invest. Dermatol. 96: 255-259, 1991). First, the cells are detached from the petridish using a cell scraper, suspended in 1 ml of homogenization buffer, and the cells are crushed using a glass homogenizer. 0.5 ml of 30% Trichloroacetic acid solution (TCA) and 50 µl of 2% butylated hydroxy toluene (BHT) ethanol solution are added to 0.5 ml of the cell ground liquid. 0.5 ml of TBA aqueous solution (375 mg / ml) was added thereto and then boiled in boiling water for 15 minutes. After cooling, absorbance at 535 nm is measured. The results were expressed based on the absorbance of the control group not treated with ultraviolet rays, and are shown in Table 2 below.

Inhibition of Cell Lipid Peroxidation by Polyethoxylated Vitamin C Derivatives A ₅₃₅ (% of control) % Inhibition Nonirradiated control 100 - No polyethoxylated vitamin C derivative 154 ± 4.2 - Ascorbic acid 100 µg / ml 98 ± 3.8 36 3-PEG ₃₅₀ -Ascorbic acid (I) 100 µg / ml 119 ± 5.1 22 2-PEG ₃₅₀ -Ascorbic acid (II) 100 µg / ml 113 ± 2.5 26 * n = 3

As can be seen in Table 2, the polyethoxylated vitamin C derivatives can very effectively prevent cell membrane lipid peroxidation by ultraviolet rays. This means that polyethoxylated vitamin C derivatives can be used for the purpose of anti-aging and anti-wrinkle by inhibiting free radical generation and lipid peroxidation by ultraviolet rays.

Thus, the following Example was performed with the polyethoxylated vitamin C derivative excellent in radical scavenging ability and lipid peroxidation inhibitory effect. However, it should be noted that the present invention is not limited only to the following examples.

Comparative Example 1.

essence Parts by weight Ascorbic acid 10.0 Concentrated glycerin 10.0 Propylene Glycol 10.0 Polyoxyethylene Cured Castor Oil 1.0 Sodium hyaluronate solution (1%) 5.0 ethanol 5.0 antiseptic Quantity Spices Quantity Pigment Quantity Purified water Remaining amount system to 100

Comparative Example 2.

Aqueous solution Parts by weight 3-PEG ₃₅₀ -Ascorbic Acid (I) 10.0 Triethanolamine Quantity Purified water to 100

Example 1.

Skin Ointment Parts by weight 3-PEG ₃₅₀ -Ascorbic Acid (I) 15 Diethyl sebacate 8 Prepayment 5 Polyoxyethylene Ole-ether Phosphate 6 Sodium benzoate Quantity vaseline to 100

Example 2.

Flexible Cosmetics Parts by weight 3-PEG ₃₅₀ -Ascorbic Acid (I) 3.0 Butylene Glycol 10.0 glycerin 10.0 Hyaluronic acid 1.0 Polyethylene oleyl ether 5.0 Polyoxyethylene Cured Castor Oil 5.0 ethanol Quantity antiseptic Quantity Spices Quantity Pigment Remaining amount Purified water to 100

Example 3.

essence Parts by weight 3-PEG ₃₅₀ -Ascorbic Acid (I) 10.0 Concentrated glycerin 10.0 Propylene Glycol 10.0 Polyoxyethylene Cured Castor Oil 1.0 Sodium hyaluronate solution (1%) 5.0 ethanol 5.0 antiseptic Quantity Spices Quantity Pigment Quantity Purified water Remaining amount system to 100

Example 4.

Nutrition Parts by weight 3-PEG ₃₅₀ -Ascorbic Acid (I) 1.0 Cetanol 1.0 Beeswax 0.5 vaseline 2.0 Squalane 6.0 Dimethyl Polysiloxane 2.0 ethanol 3.0 Concentrated glycerin 4.0 1,3 butylene glycol 4.0 Polysorbate 60 1.0 Solbitan Sesqui Olate 0.3 Carboxy polymer 0.3 Triethanolamine 0.3 antiseptic Quantity Spices Quantity Pigment Quantity Purified water Remaining amount system to 100

Example 5.

Nutrition Cream Parts by weight 2-PEG ₃₅₀ -Ascorbic Acid (II) 20.0 Stearyl alcohol 6.0 Stearic acid 2.0 Concentrated glycerin 1.0 Squalane 9.0 1,3 butylene glycol 6.0 Polysorbate 60 1.5 Polyethylene Glycol 1000 4.0 Cured Lanolin 4.0 Octyl dodecanol 10.0 Sorbitan stearate 0.8 Triethanolamine 0.5 antiseptic Quantity Spices Quantity Purified water Remaining amount system to 100

Experimental Example 3. Measurement of Percutaneous Absorption Rate

In vitro skin permeation tests were performed using the skin of hairless mice to determine the transdermal absorption of polyethoxylated vitamin C derivatives. Inject 20 μl of sample into the skin surface of 7.5 mm diameter and transfer the percutaneous absorption measuring instrument (Microette, Hanson co.).

The amount permeated during each elapsed time was quantified by liquid chromatography, and the transmittance is shown in Table 3 below.

Comparison of Percutaneous Absorption Rate of Comparative Example and Example (Unit:%) Comparative Example 1 Comparative Example 2 Example 3 After 6 hours 1.39 0.25 5.9 After 12 hours 3.19 0.86 8.5 After 24 hours 6.76 3.46 28.4

As shown in Table 3, the permeation amount of the polyethoxylated vitamin C derivative was up to three times more excellent than that of ascorbic acid, which can be predicted that the composition containing the polyethoxylated vitamin C is effective. In addition, the dosage of the polyethoxylated vitamin C derivative in the composition was superior to that in the aqueous solution. In general, surfactants and propylene glycol contained in the composition is known to increase the percutaneous absorption by acting as a percutaneous absorption promoting role.

Experimental Example 4. Storage stability test over time

Samples of Examples and Comparative Examples prepared by the above method were stored for one month in a 40 ° C thermostat, and the polyethoxylated vitamin C derivatives were calibrated by HPLC to test the storage stability over time.

Preservation stability over time (% retention) division 1 week later after 2 weeks 3 weeks later 4 weeks later Comparative Example 1 67.0 46.6 29.6 10.2 Comparative Example 2 93.7 81.1 78.6 73.7 Example 1 96.9 94.4 91.5 89.4 Example 3 97.3 95.6 93.4 91.3 Example 5 95.7 93.2 92.7 91.5

Compared with ascorbic acid, it is excellent in storage stability, and it can be seen that there is a double effect of the stability depending on the composition. In addition, the stability of the polyethoxylated vitamin C derivatives is more stable in the composition than in aqueous solution.

Experimental Example 5. Measurement of skin photoaging inhibitory effect by ultraviolet light

In this example, the effect of inhibiting skin photoaging by ultraviolet rays was tested as follows (Bisset. PL, et al. Photodermatol. Photoimmunol. Photo med 7: 56-62, 1990). 40 hairless mice of about 10 weeks of age are divided into 4 groups of 10 animals each time, followed by ultraviolet light (Westinghouse FS-40 Sunlamp × 4) at a dose of 30 mJ / ㎠ for 3 weeks a week. Investigate. Comparative examples 1, Examples 1, 3 and 5 were applied to four experimental groups 2 hours before irradiation, and respective bases were applied to the other four groups. The extent of wrinkles was determined 1 week after the last UV irradiation. Criteria were determined by four stages of no improvement, slight improvement, moderate improvement, and significant improvement compared to each base application control, and the results are shown in Table 5 below.

Inhibition effect of wrinkles caused by ultraviolet rays of embodiments according to the present invention (Marie) No improvement Minor improvements Moderate improvement A significant improvement Comparative Example 1 3 4 2 One Example 1 One 2 5 2 Example 3 2 3 3 2 Example 5 0 2 4 4

As can be seen in Table 5, the embodiments of the present invention effectively prevent the generation of wrinkles by ultraviolet rays in hairless mice. This means that the present invention can effectively prevent or reduce light aging due to ultraviolet rays when used as a topical application to skin.

As described above and as can be seen through the Examples and Comparative Examples, the present invention shows relatively high solubility in both water and organic solvents, and has high stability and skin absorption, and excellent anti-oxidation or radical scavenging function. A cosmetic composition containing a vitamin C derivative can be provided. Accordingly, the present invention can provide a cosmetic composition containing a polyethoxylated vitamin C derivative useful for the prevention or improvement of wrinkles and skin aging caused by ultraviolet rays when used as an external preparation for application to the skin, which is very useful in the cosmetic industry. to be.

Claims (4)

delete For the purpose of preventing or improving wrinkles and skin aging, the composition contains at least one of polyethoxylated vitamin C derivatives of the following general formulas (I) and (II) as a free radical scavenging agent or an antioxidant. Cosmetic composition.

Wherein PEG is (CH ₂ CH ₂ O) nOR ₁ and means an integer of n = 2-200, and R ₁ means C1-C6 lower alkyl group. The cosmetic composition for the purpose of preventing or improving wrinkles and skin aging according to claim 2, which contains 0.01 to 50% by weight of a polyethoxylated vitamin C derivative. 4. A cosmetic composition for the purpose of preventing or improving wrinkles and skin aging according to claim 3, which contains 1 to 20% by weight of a polyethoxylated vitamin C derivative.