JP5468866B2 - Topical skin preparation - Google Patents

Description

The present invention relates to a novel skin external preparation excellent in anti-aging and whitening action.

In recent years, the presence of free radicals and active oxygen has attracted attention as one of the causes of skin aging such as wrinkles and firmness of skin. Free radicals and active oxygen damage skin by decomposing, cross-linking and oxidizing biological tissues such as collagen and promote skin aging. It has also been reported that matrix metalloproteases such as collagenase are activated by ultraviolet rays and promote wrinkles and tarmi by reducing collagen in the dermis. Furthermore, it is known that hyaluronidase is activated during inflammation and lowers the molecular weight of hyaluronic acid, thereby reducing skin firmness and causing aging such as wrinkles.

In recent years, methods for blending anti-oxidants such as retinoic acid, α-hydroxy acid, retinol, tocopherol, ascorbic acid, superoxide dismutase (SOD) into cosmetics for the purpose of preventing aging such as wrinkles and tarmi are known. Yes. In addition, a method of blending a plant extract having an inhibitory effect such as collagenase or hyaluronidase or an active oxygen scavenging effect as a natural raw material is generally used. (Patent Document 1, Patent Document 2, Patent Document 3)

JP-A-7-258063 JP-A-8-175957 JP-A-8-175958

In general, pigmentation of the skin seen in spots, buckwheat, sunburn, etc. is caused by excessive melanin pigment formation by melanin-producing cells present in the skin due to hormonal abnormalities or stimulation of ultraviolet rays, which deposits in the skin. Is considered to be the cause. As one method for preventing such pigmentation, a method for suppressing excessive production of melanin is known. Conventionally, treatments for applying pigment such as hydroquinone or ascorbic acid (vitamin C) have been performed for the treatment of pigmentation.

However, as a plant-derived natural raw material having these active oxygen scavenging effects, enzyme inhibitory effects, and melanin production-suppressing effects, the genus Crosandra species used in the present invention has not been studied.

SOD used for the purpose of preventing skin aging or anti-oxidation is unstable, difficult to formulate, and vitamin E is not effective enough. Moreover, since BHT etc. which are synthetic compounds have a problem in safety | security and there exists a restriction | limiting in compounding quantity, it is not a chemical synthetic product but the natural raw material which is stable and has few side effects is desired. Similarly, it is preferable for preventing aging that it has a safe and stable collagenase and hyaluronidase inhibitory action. In addition, ascorbic acid used as an antioxidant or whitening agent has a defect such as being easily decomposed over time, and therefore, a natural preparation derived from a natural product having high stability and excellent effect is desired. Yes.

From the above, a skin external preparation that is safe and excellent in stability, excellent in anti-aging and whitening action is desired.

The inventors of the present invention have conducted screening on various plant extracts for various evaluation systems relating to beauty and health as described above. In that process, an extract obtained from the genus Crosandra plant, which is a novel ingredient in the cosmetics field, is effective for any action, and is safe and has no starch, precipitation, discoloration, or odor change. It has been found that it can be a multifunctional beauty / health material with very stable properties with little occurrence.
Under these circumstances, as a result of intensive studies, the present inventors have found that the extract of the genus Crosandra spp. Has excellent active oxygen scavenging action, collagenase inhibition, hyaluronidase inhibition and melanin production inhibiting action, and also excellent stability. I found out. Furthermore, it discovered that the skin external preparation containing the extract was safe and stable, and was excellent in anti-aging and whitening effect, and came to complete this invention.

The genus Crosandra species used in the present invention include, in general, Crosandra infundiformis and Crossandra Pungens, which are widely sold.

The extract of the genus Crosandra spp. Used in the present invention is extracted from a part of the plant body such as leaves, stems, flowers, roots or the whole plant. Preferably, those obtained by extraction from leaves and stems of plants are good. The extraction method is not particularly limited, and for example, it may be a heat extraction or a room temperature extraction.

Examples of the solvent to be extracted include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol). , Glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether) Etc.). Preferred are polar solvents such as water, lower alcohols and liquid polyhydric alcohols, and particularly preferred are water, ethanol, 1,3-butylene glycol and propylene glycol. These solvents may be used alone or in combination of two or more.

The extract may be used as it is, or may be used after concentration, dilution and filtration treatment, decolorization with activated carbon, deodorization treatment, or the like, if necessary. Further, the extracted solution may be subjected to a treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product.

In the external preparation for skin of the present invention, the above extract may be used as it is, and within the range not impairing the effect of the extract, oils and fats, waxes, hydrocarbons, fatty acids which are components used in the external preparation , Alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments, antioxidants, whitening agents, chelating agents, etc. These components can be blended.

The external preparation for skin of the present invention can be used for any of cosmetics, quasi drugs, and pharmaceuticals. Examples of the dosage form include skin lotions, creams, emulsions, gels, aerosols, essences, Examples include packs, cleaning agents, bath preparations, foundations, dusting powders, lipsticks, ointments, and poultices applied to the skin.

The amount of the extract used in the present invention is 0.0001% by weight or more, preferably 0.001 to 10% by weight in terms of solid matter, based on the total amount of the external preparation for skin of the present invention. If it is less than 0.0001% by weight, a sufficient effect is hardly expected. When the blending amount exceeds 10% by weight, the effect is hardly recognized and it is uneconomical. In addition, the addition method may be added in advance or during the production, and may be appropriately selected in consideration of workability.

Next, in order to describe the present invention in detail, examples of production of the extract used in the present invention, formulation examples and experimental examples will be given as examples, but the present invention is not limited thereto. In the examples, the part of the amount is part by weight, and% is% by weight.

Production Example 1 Hot water extract of Crosandra infundiformis Former was added to 400 g of purified water to 20 g of a dried product of Crossandra infundiformis and extracted at 95-100 ° C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 2.2 g of a hot water extract of Closandra infundibriformis.

Production Example 2 50% Ethanol Extract of Crosandra infundiformis Add 1 L of 50% ethanol to 100 g of a dry product of Crosandra infundiformis and extract at room temperature for 7 days. Thereafter, the mixture was filtered, and the filtrate was concentrated to dryness to obtain 4.2 g of a 50% ethanol extract of Closandra infundiformis.

Production Example 3 Ethanol Extract of Crosandra infundiformis Add 1 L of ethanol to 100 g of dried plant of Crosandra infundiformis and extract at room temperature for 7 days, followed by filtration. The filtrate was concentrated and dried to obtain 3.9 g of an ethanol extract of Closandra infundiformis.

Production Example 4 50% 1,3-Butylene Glycol Extract of Closandra infundiformis 50% 1,3-Butylene Glycol in 20 g of dried whole plant of Crossandra infundiformis 400 mL was added and extracted at room temperature for 7 days, followed by filtration to obtain 380 g of a 50% 1,3-butylene glycol extract of Closandra infundibriformis.

Production Example 5 Hot Water Extract of Crosandra Pungens 400 mL of purified water was added to 20 g of a dried product of the whole plant of Crossandra Pungens, extracted at 95-100 ° C. for 2 hours, filtered, and filtrated. Was concentrated and freeze-dried to obtain 2.5 g of a hot water extract of Crosandra pungens.

Formulation Example 1 Lotion Prescription Formulation Amount (parts)
1. Crosandra Infundi briformis hot water extract (Production Example 1) 1.0
2. 1,3-butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7). Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Perfume proper amount11. [Manufacturing method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved in purified water, and both are mixed and filtered to obtain a product.

Comparative Example 1 A conventional lotion was obtained by replacing the hot water extract of Closandra infundiformis in the conventional lotion formulation example 1 with purified water.

Formulation Example 2 Cream Formulation Amount (parts)
1. 50% ethanol extract of Kurosandra infundibriformis (Production Example 2) 0.5
2. Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.1
11. Methyl paraoxybenzoate 0.2
12 Ethyl paraoxybenzoate 0.05
13.1,3-Butylene glycol 8.5
14 [Manufacturing method] Components 2 to 9 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 11 to 14 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Comparative Example 2 A conventional cream was obtained by replacing the 50% ethanol extract of Closandra infundiformis in the conventional cream formulation example 2 with purified water.

Formulation Example 3 Latex Formulation Formulation amount (parts)
1. Crosandra pungens hot water extract (Production Example 5) 0.01
2. Squalane 5.0
3. Olive oil 5.0
4). Jojoba oil 5.0
5. Cetanol 1.5
6). Glycerol monostearate 2.0
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Polyoxyethylene sorbitan monooleate (20E.O.) 2.0
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12 Methyl paraoxybenzoate 0.2
13. [Manufacturing method] Components 2 to 8 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 10-13 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 9 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 4 Gel formulation Formulation Amount (parts)
1. Ethanol extract of Kurosandra infundibriformis (Production Example 3) 1.0
2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
5. Perfume appropriate amount 6.1,3-butylene glycol 5.0
7). Glycerin 5.0
8). Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. [Production method] Ingredients 2 to 5 and ingredients 1 and 6 to 11 are uniformly dissolved in purified water, and the two are mixed to obtain a product.

Formulation Example 5 Pack Formulation Amount (parts)
1. Black water extract of Closandra infundibriformis (Production Example 1) 1.0
2. 50% 1,3-butylene glycol extract of Closandra infundibriformis (Production Example 4) 0.1
3. Polyvinyl alcohol 12.0
4). Ethanol 5.0
5.1,3-Butylene glycol 8.0
6). Methyl paraoxybenzoate 0.2
7). Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
8). Citric acid 0.1
9. Sodium citrate 0.3
10. Perfume proper amount11. [Production Method] Components 1 to 11 are uniformly dissolved in purified water to make a total amount of 100 to obtain a product.

Formulation Example 6 Foundation Formulation Amount (parts)
1. 50% ethanol extract of Closandra infundibriformis (Production Example 2) 1.0
2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20E.O.) 1.0
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7). Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Sodium carboxymethylcellulose 0.1
10. Bentonite 0.5
11. Propylene glycol 4.0
12 Triethanolamine 1.1
13. Methyl paraoxybenzoate 0.2
14 Titanium dioxide 8.0
15. Talc 4.0
16. Bengala 1.0
17. Yellow iron oxide 2.0
18. Perfume proper amount19. [Manufacturing method] Components 2 to 8 are heated and dissolved in purified water to a total amount of 100, and kept at 80 ° C to obtain an oil phase. Swell component 9 well in component 19, then add components 1 and 10-13 and mix uniformly. To this, components 14 to 17 pulverized and mixed with a pulverizer are added, and the mixture is stirred with a homomixer and kept at 75 ° C. to obtain an aqueous phase. The oil phase is added to this aqueous phase with stirring, cooled, component 18 is added at 45 ° C., and cooled to 30 ° C. with stirring to give a product.

Formulation Example 7 Bath preparation Formulation Formulation amount (parts)
1. Crosandra Infundi briformis hot water extract (Production Example 1) 5.0
2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Appropriate amount 4. Perfume appropriate amount 5. [Manufacturing method] Ingredients 1 to 5 are mixed uniformly with sodium sulfate to make a product.

Formulation Example 8 Ointment Formulation Formulation amount (parts)
1. Crosandra Infundi briformis hot water extract (Production Example 1) 0.01
2. 50% 1,3-butylene glycol extract of Closandra infundibriformis (Production Example 4) 0.5
3. Polyoxyethylene cetyl ether (30E.O.) 2.0
4). Glycerol monostearate 10.0
5. Liquid paraffin 5.0
6). Cetanol 6.0
7). Methyl paraoxybenzoate 0.1
8). Propylene glycol 10.0
9. [Production Method] Components 3 to 6 are heated and dissolved and mixed with purified water to a total amount of 100, and kept at 70 ° C. to obtain an oil phase. Ingredients 1, 2, and 7-9 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled to 30 ° C. with stirring to obtain a product.

Next, experimental examples will be given to explain the effects of the present invention in detail.

Experimental Example 1 Free radical scavenging and removing action The free radical scavenging and removing action was evaluated. Ascorbic acid was used as a positive control. As a free radical model, α, α-diphenyl-β-picrylhydrazyl (hereinafter referred to as DPPH), which is a stable free radical, is used and reacted with a sample at a certain rate for a certain period of time. Was measured from the decrease in absorbance at a wavelength of 517 nm.

The method for measuring free radical scavenging / removing action used the extract described in Production Examples 1, 2, 3 and 5.
Each sample was added to 2 mL of 0.1 M acetate buffer (pH 5.5) added to a final concentration of 0.01 mg / mL (ascorbic acid 0.01 mg / mL), and 2 mL of absolute ethanol and 0.5 mM DPPH absolute ethanol 1 mL of the solution was added to prepare a reaction solution. In the case of an oil-soluble sample, the sample was added to 2 mL of absolute ethanol to prepare a reaction solution. Then, it was made to react at 37 degreeC for 30 minute (s), and the light absorbency (A) of wavelength 517nm was measured by using water as a control. Moreover, the light absorbency (B) was measured using the purified water instead of the sample as a blank. The free radical scavenging removal rate was calculated from the following equation.
Free radical scavenging removal rate (%) = (1−A / B) × 100

The test results are shown in Table 1. It was confirmed that the extract of Closandra infundiformis and Closandra pungens of the present invention has a stable and excellent free radical scavenging and removing action. Ascorbic acid was inactivated by heat treatment at 100 ° C. for 1 hour, but the extract of Closandra infundiformis and Crosandra pungens of the present invention did not change in activity.

Experimental Example 2 Inhibition test of melanin production using B16 mouse melanoma B16 mouse melanoma in the logarithmic growth phase was seeded with 3 × 10 ⁴ cells in a φ60 mm dish, and Eagles'MEM (10%) containing a sample having a final concentration of 1 μg / mL. Fetal calf serum-containing) medium was added and cultured under conditions of 37 ° C. and 5% CO ₂ . After 5 days of culture, the cells were detached from the dish, and the cells were sonicated, and then treated with 4N NaOH for 2 hours at 60 ° C. D. 475 nm was measured. In addition, the protein quantification is performed for the cell lysate after sonication by Lowry's method (J. Biol. Chem., 193, 265-275, 1951), and the amount of melanin per amount of protein is compared to suppress melanin production. It was used as an effect index.

The test results are shown in Table 2. It was confirmed that the extracts of Closandra infundiformis and Closandra pungens of the present invention have an excellent melanin production inhibitory action.

Experimental Example 3 Collagenase Inhibition Test Using Examples 1, 2, 3 and 5 as samples, the collagenase inhibitory action was measured. 50 μL of a 50 U / mL collagenase Type IV (Sigma) aqueous solution was added as an enzyme solution to 50 μL of a sample solution having a final concentration of 1 mg / mL. 400 μL of 20 mM calcium chloride-containing Tris-HCl buffer (pH 7.1) containing 0.39 mg / mL Pz-peptide (Pz-Pro-Leu-Gly-Pro-D-Arg-OH, Sigma) as a substrate solution was added. After mixing at 37 ° C. for 30 minutes, 0.5 mL of 25 mM citric acid was added to stop the reaction. Ethyl acetate 2.5mL was added and the light absorbency in 320 nm was measured about the ethyl acetate layer. Moreover, the inhibitory action of each sample was calculated by the inhibition rate calculated | required from the following formula. For the control, purified water was used instead of the sample, and 20 mM calcium chloride-containing Tris-HCl buffer (pH 7.1) was used instead of collagenase as a blank.
Inhibition rate (%) = [1- (C−D) / (A−B)] × 100
A: Absorbance at 320 nm of control (OD 320)
B: O. D. 320
C: Sample O.D. D. 320
D: Sample blank O.D. D. 320

The results of these experiments are shown in Table 3. As a result, the extract of Closandra infundiformis and Closandra pungens of the present invention showed an excellent collagenase inhibitory action.

Experimental Example 4 Hyaluronidase Inhibition Test Using Production Examples 1, 2, 3 and 5 as samples, hyaluronidase inhibitory activity was measured according to a method applying the Morgan-Elson method [Food Hygiene Journal, 31, 3 (1990)]. . That is, 175 μL of 0.1 M acetate buffer (pH 4.0) was added to a sample solution with a final concentration of 0.1 mg / mL, and the hyaluronidase enzyme activity was 250 U / mL, and the hyaluronic acid concentration was 0.4 mg / mL. The total volume was adjusted to 500 μL so that the compound 48/80 of the agent was 0.08 mg / mL, and then the hyaluronidase reaction was carried out at 37 ° C. for 40 minutes. After the reaction, a p-dimethylaminobenzaldehyde reagent was added to develop color, and the absorbance at 585 nm was measured. Moreover, the inhibitory action of each sample was calculated by the inhibition rate calculated | required from the following formula. For the control, purified water was used instead of the sample solution, and 0.1 M acetate buffer (pH 4.0) was used instead of hyaluronidase as a blank.
Inhibition rate (%) = [1- (C−D) / (A−B)] × 100
A: Absorbance at 585 nm of control (OD 585)
B: O. D. 585
C: Sample O.D. D. 585
D: Sample blank O.D. D. 585

The results of these experiments are shown in Table 4. As a result, the extract of Crosandra infundiformis and Crosandra pungens of the present invention showed an excellent hyaluronidase inhibitory action.

Experiment 5 Use test 1
One month use for 20 women (22 to 48 years old) using the lotion of Formulation Example 1, the cream of Formulation Example 2, the conventional lotion of Comparative Example 1 and the conventional cream of Comparative Example 2. A test was conducted. After use, the effect of improving skin wrinkles and tarmi was determined by a questionnaire.

The test results are shown in Table 5. As a result, the external preparation for skin containing the extract of the present invention showed an excellent wrinkle and tarmi improving action. During the test period, there was no skin problem and there was no problem with safety. There was also no problem with the deterioration of the prescription ingredients.

Experiment 6 Use test 2
Using the lotion of Formulation Example 1, the cream of Formulation Example 2, the conventional lotion of Comparative Example 1 and the conventional cream of Comparative Example 2, targeting 20 women (22 to 48 years old) suffering from spots and freckles A one month use test was conducted. After use, the effect of improving spots and freckles was judged by a questionnaire.

The test results are shown in Table 6. As a result, the external preparation for skin containing the extract of the present invention showed an excellent effect of improving spots and freckles. During the test period, there was no skin problem and there was no problem with safety. There was also no problem with the deterioration of the prescription ingredients.

From the above, the extract of the plant of the genus Crosandra has excellent antioxidative action, collagenase inhibition, hyaluronidase inhibition and melanin production inhibitory action, and is also excellent in stability. Furthermore, the external preparation for skin containing these extracts showed safe and excellent anti-aging and whitening action. Therefore, the skin external preparation containing the extract of the genus Crosandra plant of the present invention is particularly effective as a skin external preparation for anti-aging or whitening.

Claims (4)

A whitening agent comprising an extract of Crossandra infundiformis. Antioxidant characterized by containing an extract of Crossandra inundiformis . Collagenase inhibitor characterized by containing an extract of Crossandra infundiformis . A hyaluronidase inhibitor characterized by containing an extract of Crossandra infundiformis .