KR20020011719A - A composition for external application for skin whitening - Google Patents

Abstract

PURPOSE: Provided is a composition for external application for skin whitening, which composition prevents over pigmentation and makes the color of melanin pale. CONSTITUTION: The composition comprises 0.001-5 wt.% of retinoid, 0.001-5 wt.% of vitamin C, 0.001-5 wt.% of persimmon acid derivative, and 0.001-10 wt.% of a botanical mixture of job's tear/mung beans/black beans, and 0.001-0.5% of salicylic acid as an active ingredient to suppress the generation of melanin and make its color pale. Therefore, it has an excellent whitening effect on skin.

Description

Whitening composition for external application for skin {A composition for external application for skin whitening}

The present invention relates to a whitening skin external composition for protecting skin pigment overdeposition and helping to thin the melanin pigment deposited on the skin.

In general, human skin color is mainly determined by the activity and distribution of melanocytes (melanocytes) that make melanin pigments. Is determined. Melanin pigment is dopa (DOPA, dihydroxy phenylalanine) by tyrosinase, which is a kind of amino acid in the human body, which is contained inside the melanocytes in the basal layer of the epidermis. Through a series of complex oxidation processes that are converted and continued, they eventually form a dark brown pigment called melanin, a polymer. In addition, various internal and external environmental factors, such as ultraviolet rays, medications, hormones, and genetic predisposition, act as factors of melanin synthesis. This melanin pigment is widely distributed to the surrounding keratinocytes through the dendrite of melanocytes to determine the color of the skin.

Melanin in the epidermal layer on the outside of the skin acts as a sunscreen and protects the skin organs under the dermis and also captures free radicals and free radicals generated in the skin. Plays a useful role in protecting

However, dyskinesia such as blemishes, freckles, and senile plaques is caused by abnormally activated melanin production in melanocytes, resulting in excessive melanin production and deposition. Such hyperpigmentation can put a serious mental burden on the skin's beauty point of view and interfere with normal social activities. In ancient times, Asian women have preferred white and fair skin, which has been an important standard of beauty.

therefore. The development of whitening agents for the treatment of skin pigmentation disorder and satisfying cosmetic needs is being actively made. Specific examples thereof include inhibitors that inhibit tyrosinase activity such as kojic acid, arbutin and the like, hydroquinone, vitamin A, vitamin C and derivatives thereof. However, they are limited in their use due to insufficient skin safety, stability in formulations and whitening effects.

Accordingly, the present inventors have studied to find a substance to solve the above problems, vitamin C, licorice derivatives and mung bean / black soybean with retinoids that have excellent whitening efficacy but are limited in use due to instability and skin irritation Safe and excellent whitening without irritation, sensitization, mutagenicity if BHA is used to protect skin pigment overdeposition by using plant mixture material composed of Yulmu and to thin the color of melanin pigment deposited on skin in 2 steps It has been found that the effect is achieved and the present invention has been completed.

Accordingly, it is an object of the present invention to provide a topical skin composition having excellent skin whitening effect and low skin side effects.

The above and other objects, features and advantages of the present invention will become apparent to those skilled in the art from the following detailed description.

In order to achieve the above object, the whitening skin external composition of the present invention is 0.001-5% by weight of retinoid, 0.001-5% by weight of vitamin C, 0.001-5% by weight of licoriceic acid derivative, 0.001- 0.001 plant mix raw material. A whitening composition containing 10% by weight and 0.001 to 0.5% of BHA is characterized by containing 0.01-25% by weight relative to the total weight of the composition.

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

Retinoids are retinol derivatives or mixtures thereof, such as retinol, retinic acid, retinyl palmitate, retinyl acetate, retinyl oleate, and the like, which promote the proliferation and differentiation of cells constituting the epidermis of the skin, thereby reducing skin melanin per unit area. It is an excellent whitening ingredient that shows the whitening effect by reducing the content of pigment. However, although retinoids have excellent effects, their use is limited in cosmetics due to their instability and irritation on the skin. Therefore, many efforts have been made to stabilize or reduce the irritation with large liquid crystals or double capsules. Has been.

The licorice derivatives used in the present invention are licorice extract, licorice acid (glyciletin acid), glycyrrhetin (glycyrrhetin), metal salts such as zinc and potassium of licorice acid, stearyl glycyrrhetinate (stearyl glycyrrhetinate) and its Other licorice derivatives and mixtures thereof have anti-inflammatory effects, anti-allergic effects, tyrosinase activity inhibitory effects, and the like, but there is a problem in their stability.

In addition, vitamin C is excellent in whitening effect, but very unstable and easily oxidized in an aqueous solution, the whitening effect is not persistent, there is a severe irritation to the skin.

On the other hand, botanical mixture of mung bean / black bean / yield in proper ratio is powder formulation and isoflavone rich like daidzin, genistin and palmitic acid, stearic acid and other fatty acids to give effect as emollient. It also contains phospholipids such as phosphatidyl choline, which helps to stabilize the whitening composition.

BHA is a beta hydroxy acid used as a typical raw material salicylic acid. It acts on the epidermis and promotes turn-over of the stratum corneum, which is effective in lightening the color of the melanin produced.

The external preparation composition of the present invention can provide an excellent whitening effect while minimizing the skin irritation generated by the use of retinoid alone by using the retinoid, licorice derivative, vitamin C, which is a problem as described above in combination with a plant material, BHA. .

Meanwhile, the whitening skin external composition of the present invention is 0.001-5% by weight of retinoid, 0.001-5% by weight of vitamin C, 0.001-5% by weight of licorice derivatives, 0.001-10% by weight of plant mixture, BHA 0.001 It is characterized by containing 0.01-25% by weight of the whitening composition containing ˜0.5% to the total weight of the composition, the content of each component is the minimum concentration that is effective at the level of cell culture and the maximum that can be formulated in terms of formulation It was determined over a range of concentrations.

The external preparation composition for skin of the present invention is used for the purpose of treating or preventing skin pigmentation disorders such as blemishes, freckles, and senile plaques, and is not particularly limited in the formulation thereof. For example, supple cosmetics and nutrient cosmetics , Cosmetic creams, nourishing creams, packs, gels, or cosmetic compositions having a formulation of a skin adhesive type, and may also be transdermal formulations such as lotions, ointments, gels, creams, patches or sprays.

In addition, in the skin external preparation composition for whitening of each formulation, other ingredients in addition to the above components may be appropriately selected and blended by those skilled in the art without difficulty according to the formulation or use purpose of the other skin external preparation composition.

Hereinafter, the present invention will be described in more detail with reference to various examples, but the present invention is not limited to these examples.

Reference Example 1 Plant Mixing Material Manufacturing Process

Mung bean / black bean / yield was mixed in an appropriate ratio to prepare in the following order. 1) After washing with clean water to remove water and dried for 48 hours in the shade. 2) After the water was added to the water bath, 10 times the total volume of water was added, and the cooling capacitor was attached and steamed at 90 ° C. for 1 hour while preventing the active ingredient from evaporating. 3) After cooling down completely, it was dried for 24 hours in a well-ventilated shade. 4) The process of 2) ~ 3) was repeated eight times and then lyophilized. 5) Jet mill treatment to prepare a fine powder of the final 5 ~ 10㎛.

Test Example 1 Measurement of Melanin Inhibition Effect Using Pigment Cells

Treatment with the composition of Table 1 using rat pigment cells to measure the melanin production inhibitory effect.

Mel-Ab cells are derived from C57BL / 6 mice, 10% fetal bovine serum, 10 nM 12-O-tetradecanoylphorbol in Dulbecco's modified Eagle's media (DMEM). ) -13-acetate and 1 nM cholera toxin were added and cultured at 37 ° C. and 5% CO ₂ . After incubating the cells at a concentration of 10 ⁵ cells / well in a 24-well plate and confirming the cell attachment, the cells were cultured for 3 days by adding a constant concentration of test substance to the cell culture. Here, the test substance is dissolved in each solvent of the composition of Table 1 in a specific solvent, and then dissolved in a mixed solvent of propylene glycol: ethanol: purified water is 5: 3: 2, diluted with test concentration and mixed in the same ratio It is.

After removing the culture solution, washed with PBS and dissolved the cells with 1N sodium hydroxide to measure the absorbance at 400nm, to calculate the melanin production inhibition in accordance with Equation 1 shown in Table 2 (Dooley's method) .

(Equation 1)

Melanogenesis inhibition rate (%) = 100-({absorbance of each test substance} over {

Brightness} TIMES 100)

Whitening composition ingredient content(%) Retinoid ( ¹⁾ 10 Vitamin C ⁽²⁾ 10 Licorice derivatives ⁽³⁾ 10 Plant Mix Extract ⁽⁴⁾ 10 Salicylic Acid 0.5 Note ¹ ) Retinol 10S (BASF, Germany); Retinol 10%, soybean oil 89%, BHT and 1% ² ) Ascorbic acid ultra fine powder, ascorbic acid microgranule (Roche, France) Note ³ ) 18-beta-glycitinic acid (Maruzen, Japan) Note ⁴ ) Reference Example 1

Melanin production inhibitory effect Test substance (treatment concentration) Melanin production inhibition rate (%) Whitening composition 0.02% 80 Whitening Composition 0.01% 50 Whitening Composition 0.001% 20 Kojisan 0.02% 50 Control 0

From the above Table 2, it can be seen that the external preparation composition of the present invention shows a very high melanin production inhibitory effect even at a low concentration of about 0.01%, compared to kojic acid, which is known to have excellent whitening effect.

<Test Example 2> Evaluation of the whitening effect at the animal level

Brown motnea pigs (Tortoiseshell guinea pigs) are animals that cause pigmentation due to ultraviolet rays, PUVA, allergic reactions, etc., like humans. After removing the hair, a wide range of areas can be used. Pigmentation is produced by the method enumerated below, and the improvement effect of pigmentation can be verified by the method of apply | coating the whitening composition to the pigmentation site | part. In addition, substances whose effects have been recognized by this method are useful in primary in vivo screening methods because they have a high probability of having an effect on evaluation in human ultraviolet pigmented plaques.

① Preparation of UV Pigment

Preparation of pigmentation by ultraviolet (UVB) is performed by attaching a light shielding aluminum foil having six square windows of 3 × 3 cm to the skin from which the hairs behind the brown molot are removed, followed by an SE lamp (wavelength 290 to 320 nm, Toshiba). ) Was irradiated with ultraviolet light (UVB) (total amount of irradiation energy 1350mJ / cm ² ). After irradiation, the aluminum foil was peeled off and the whitening effect of the test substance was evaluated by the application method as follows. Pigmentation after UV irradiation appears 2-3 days later, reaching peak after about 2 weeks. It is important that the resulting UV pigments have the same color tone and that no stains occur. Individuals with poor UV pigment formations should not be used for good results.

② Application of Composition

After ultraviolet irradiation, the composition of Table 1 began to be applied about 14 days after the pigmentation is the highest, that is, the pigmentation is formed. The number of coatings was continued once or twice a day for 50 days. The composition was prepared by dissolving and diluting in a mixed solvent of propylene glycol: ethanol: water = 5: 3: 2, applying with a cotton swab, and applying a solvent to other sites. Along with the determination of the effect, the cumulative stimulus was also observed.

③ judgment of effect

The effect was determined by measuring the degree of black and white of the skin using a color difference meter (Minolta CR2002). L * a * b * colorimeter is used for displaying a color, and in this invention, L * value (brightness) was mainly used as an index. The L * value is calibrated with a standard whiteboard and the measurement is measured evenly on the pigment deposit by repeating the measurement five times or more at one site. The difference in skin color (ΔL *) at the start and completion of the application was calculated according to Equation 2 below, which is shown in Table 3. The whitening effect is determined by comparing ΔL * between the sample application site and the control site. When ΔL * value is about 2, the whitening effect of the deposited pigment is clear, and when about 1.5 or more, the whitening effect may be determined. .

(Equation 2)

TRIANGLE L * = L * value 50 days after application-L * value at the time of application

Substance (treatment concentration) Whitening effect (△ L) Whitening Composition 1.0% 2.31 Whitening composition 0.2% 1.73 Kojisan 1.0% 0.78 Control 0.82

From the results of Table 3, the composition of the present invention can be seen that the whitening of the pigment deposited at a concentration of 1.0% has a clear and whitening effect at a concentration of 0.2%. This resulted in the deposition being counteracted.

<Example 1 and Comparative Example 1-7>

In order to test the whitening effect on human skin, the raw materials 1-6 and 8 of Table 4 were mixed, dissolved at 70 ° C., and used as water parts. In addition, raw materials 7 and 9-19 were melt | dissolved at 70 degreeC, and it was set as the oil part. The oil part was added to the water part, stirred with a homomixer (Tokushu Kika Co., Ltd., Japan), and first emulsified. After removing bubbles, the mixture was cooled to room temperature and used in Example 1 and Comparative Examples 1-7.

ingredient Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 1. Purified water To 100 To 100 To 100 To 100 To 100 To 100 To 100 To 100 2. Glycerin 8.0 8.0 8.0 8.0 8.0 8.0 8.0 8.0 3. Butylene Glycol 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4. Hyaluronic Acid Extract 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5. Beta Glucan 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 6. Carbomer 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 7. Retinol 0.1 - 0.1 - - - - - 8. Vitamin C 0.1 - - 0.1 - - - - 9. Glycyretinic Acid 0.5 - - - 0.5 - - - 10. Plant Blend Raw Materials 0.5 - - - - 0.5 - - 11.Salicylic acid 0.5 - - - - - 0.5 - 12. Kojisan - - - - - - - 1.0 13. Caprylic Capric Triglyceride 8.0 8.0 8.0 8.0 8.0 8.0 8.0 8.0 14. Squalane 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 15. Polysorbate 60 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 16. Sorbitan Stearate 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 17. Cetearyl Alcohol 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 18. Preservative Quantity Quantity Quantity Quantity Quantity Quantity Quantity Quantity 19. Incense Quantity Quantity Quantity Quantity Quantity Quantity Quantity Quantity 20. Triethanolamine 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1

Experimental Example 3 Safety Confirmation Experiment on Human Skin

Prior to testing the whitening effect on the human skin of the compositions of Example 1 and Comparative Examples 1-7, a human skin cumulative stimulation test was conducted to verify the skin safety of the compositions.

A total of nine healthy 24-year-old adults will receive a total of nine 24-hour cumulative patches on the upper forearm every other day. The patch method uses a fin chamber or a similar kind of chamber, and 15 µl of the composition is added dropwise per chamber, and the patch is applied, and the degree of reaction on the skin is expressed by the following equation. Calculation according to 3 and the results are shown in Table 5. At this time, ± 1 point in the reaction, + 2 points, + ++ gives a score of 4 (the highest score), when the average response is less than 3 is determined as a safe composition.

(Equation 3)

Average responsiveness = ({Number of respondents TIMES responsiveness} over {Total number of subjects TIMES highest score}

TIMES 100) DIV Total Inspection Count

Test substance Number of subjects with response Average reactivity 1 week 2 weeks 3 weeks Primary Secondary 3rd 4th 5th 6th 7th 8th 9th ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ Comparative Example 1 3-- --- --- --- --- --- --- --- --- 0.42 Comparative Example 2 6 2- 5 1- 4 1- 4 - - 2 - - 2 - - One - - --- --- 4.44 Comparative Example 3 3 1- 3-- 2 - - One - - --- --- --- --- --- 1.53 Comparative Example 4 3-- One - - --- --- --- --- --- --- --- 0.56 Comparative Example 5 One - - --- --- --- --- --- --- --- --- 0.14 Comparative Example 6 3 1- 3-- 2 - - One - - --- --- --- --- --- 1.53 Comparative Example 7 4 - - 2 - - --- --- --- --- --- --- --- 0.83 Example 1 4 - - One - - One - - --- --- --- --- --- --- 1.11 Inspector 20 20 20 20 20 20 20 20 20

From the results of Table 5, in the composition used in Test Example 3, the retinoid-containing Comparative Example 2 was shown to cause light irritation on the skin, the remaining compositions do not show a distinct cumulative stimulation pattern than when used alone The combination of vitamin C, licorice derivatives, plant mixtures and salicylic acid at an appropriate concentration was found to be advantageous in terms of skin safety.

Test Example 4 Whitening Effect Test on Human Skin

After attaching an opaque tape with 6 holes of 1.5cm diameter to the upper forearm of 12 subjects, 12 healthy males were exposed to UVB at 1.5-2 times the minimum erythema dose (MinimalErythema Dose). The darkening of the skin was induced by irradiation, and the contrast of the skin was measured using a color difference meter two months after the test substances were applied. Each test substance was applied to the external preparations of Example 1 and Comparative Examples 1-7 twice daily, morning and evening.

The determination of the effect was determined by obtaining an "L" value representing the skin's contrast as in animal testing (unburned Korean skin color generally ranges between 50 and 70).

When the test material is effective, the L value is gradually increased, and the comparison between the test materials is calculated according to the following equation (4) based on the difference (△ L) of the skin color at the start and the completion time of the application. Table 6 shows.

(Equation 4)

TRIANGLE L = L value at the last edge of test substance application-L value before test substance application

Whitening effect of composition at human level Test substance Whitening effect (△ L) Example 1 3.98 Comparative Example 1 1.54 Comparative Example 2 2.53 Comparative Example 3 1.62 Comparative Example 4 1.75 Comparative Example 5 2.01 Comparative Example 6 2.05 Comparative Example 7 2.83 Control 1.33

As can be seen in Table 6, the composition containing the retinoids, vitamin C, licorice derivatives, plant mixtures, salicylic acid is superior in the whitening effect in the human body, and the whitening effect compared to the composition containing each alone It can be seen that the whitening effect is much superior to kojic acid, which is known to be excellent, and does not show skin irritation that may occur in the composition containing the retinoid, indicating a very safe and effective whitening effect.

<Formulation Example 1> Milk skin lotion

1. Purified water To 100 2. Glycerin 8.0 3. Butylene glycol 4.0 4. Hyaluronic Acid Extract 5.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. Whitening Composition * 10.0 8. Caprylic Capric Triglycerides 8.0 9. Squalane 5.0 10. Polysorbate 60 1.5 11.Sorbitan Stearate 0.4 12. Cetearyl Alcohol 1.0 13. Preservative Quantity 14. Incense Quantity 15. Pigment Quantity 16. Triethanolamine 0.1 Note *) It is a composition containing all five ingredients (retinoid, vitamin C, licorice derivative, plant mixture, salicylic acid) identified in the composition and function of the invention.

<Formulation Example 2> Nutrition Cream

1. Purified water To 100 2. Glycerin 5.0 3. Butylene Glycol 4.0 4. Carbomer 0.1 5. Beta Glucan 7.0 6. Liquid paraffin 6.0 7. Whitening Composition * 5.0 8. Caprylic Capric Triglycerides 3.0 9. Squalane 5.0 10. Cetearyl Glucoside 1.5 11.Sorbitan Stearate 0.4 12. Polysorbate 60 1.2 13. Preservative Quantity 14. Incense Quantity 15. Pigment Quantity 16. Triethanolamine 0.1 Note *) It is a composition containing all five components (retinoid, vitamin C, licorice derivative, plant mixture, salicylic acid) identified in the composition and function of the invention.

<Formulation Example 3> Massage Cream

1. Purified water To 100 2. Glycerin 5.0 3. Butylene Glycol 4.0 4. Carbomer 0.1 5. Beta Glucan 1.0 6. Liquid paraffin 45.0 7. Whitening Composition * 1.0 8. Caprylic Capric Triglycerides 3.0 9. Beeswax 1.0 10. Cetearyl Glucoside 1.5 11.Sesqui oleic acid sorbitan 0.9 12. Vaseline 3.0 13. Preservative Quantity 14. Incense Quantity 15. Pigment Quantity 16. cetostealialcohol 3.0 Note *) It is a composition containing all five components (retinoid, vitamin C, licorice derivative, plant mixture, salicylic acid) identified in the composition and function of the invention.

<Formulation Example 4> Pack

1. Purified water To 100 2. Glycerin 4.0 3. Polyvinyl Alcohol 15.0 4. Haaruronic Acid Extract 5.0 5. Beta Glucan 3.0 6. Allantoin 0.1 7. Whitening Composition * 5.0 8. Nonyl Phenyl Ether 0.4 9. Polysorbate 60 1.2 10. Preservative Quantity 11. Incense Quantity 12. Pigment Quantity 13. Ethanol 6.0 Note *) It is a composition containing all five components (retinoid, vitamin C, licorice derivative, plant mixture, salicylic acid) identified in the composition and function of the invention.

<Formulation Example 5> Ointment

1. Purified water To 100 2. Glycerin 8.0 3. Butylene Glycol 4.0 4. Carbomer 0.1 5. Beta Glucan 7.0 6. Liquid paraffin 5.0 7. Whitening Composition * 10.0 8. Caprylic Capric Triglycerides 3.0 9. Squalane 1.0 10. Cetearyl Glucoside 1.5 11.Sorbitan Stearate 0.4 12. Cetearyl Alcohol 1.0 13. Preservative Quantity 14. Incense Quantity 15. Pigment Quantity 16. Beeswax 4.0 Note *) It is a composition containing all five components (retinoid, vitamin C, licorice derivative, plant mixture, salicylic acid) identified in the composition and function of the invention.

<Formulation Example 6> Oil

Amount 100.0 1. Squalane 5.0 2. Macadamia Nut Oil 5.0 3. Jojoba Oil 1.0 4. Crude colostrum 0.5 5. Wild Rose Seed Extract 20.0 6. Whitening Composition * 0.01 7. Carlylic Katric Triglycerides 30.0 8. Liquid paraffin Remaining amount 9. Incense Quantity Note *) It is a composition containing all five components (retinoid, vitamin C, licorice derivative, plant mixture, salicylic acid) identified in the composition and function of the invention.

As described above, the topical skin composition comprising the retinoid, vitamin C, licorice derivative, plant mixture extract and salicylic acid provided by the present invention prevents skin pigmentation such as blemishes, freckles and sunburned skin. It can be seen that the skin whitening effect such as thinning the color of the melanin pigment deposited on the skin.

Claims (3)

A composition comprising a whitening composition containing 0.001-5% by weight of retinoid, 0.001-5% by weight of vitamin C, 0.001-5% by weight of licorice derivatives, 0.001-10% by weight of plant mixtures, and 0.001-0.5% of salicylic acid A skin external preparation composition for whitening, containing 0.01-25% by weight based on the weight. The skin external preparation composition for skin whitening according to claim 1, wherein the plant mixture is a mixture of mung beans, black beans, and yulmu. The whitening composition for skin whitening according to claim 1, wherein the topical skin composition has a transdermal dosage form such as lotion, research, gel, cream, patch or spray.