JPH09295931A - Cosmetic - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a cosmetic used for treating pigmentation of skin such as stain, freckle or sunburn caused by excess production of melanin pigment and having high safety and excellent beautifying effect. SOLUTION: This cosmetic contains chloropyramine represented by the formula or its hydrochloride. A blend amount of chloropyramine is 0.0001 to 10wt.%, preferably 0.01-1.0wt.% based on total amount of the cosmetic or beautifying and whitening agent. Oils and fats and surfactant, etc., which can be used for cosmetics or medicines are blended in the cosmetic or the beautifying and whitening agent.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to cosmetics and whitening agents containing chloropyramine.

[0002]

2. Description of the Related Art Pigmentation of skin, which is generally seen in spots, freckles, sunburns, etc., is attributed to the excessive production of melanin pigment by melanin pigment-producing cells present in the skin. For the treatment of this pigmentation, treatments for degrading melanin (that is, external use of hydroquinone and its derivatives) and treatments for externally using arbutin, glutathione, and ascorbic acid as thyrodinase activity inhibitors have been conventionally performed.

[0003]

However, the conventional ones, except for hydroquinone, are not sufficiently effective for treating this pigmentation because their effects are extremely slow. Although hydroquinone is effective, it is sensitizing, and allergic contact dermatitis occurs as a side effect, so its use is restricted in Japan and its formulation is unstable. In view of such circumstances, the inventors of the present invention have conducted research to obtain a cosmetic that is highly safe and has an excellent whitening effect, and as a result, chloropyramine exhibits a sufficient whitening effect,
They have found that they are extremely safe, and have completed the present invention based on this finding.

[0004]

[Means for Solving the Problems] That is, the present invention provides a cosmetic and a whitening agent characterized by containing chloropyramine. Chloropyramine used in the present invention is a compound represented by the general formula (Formula 1) or a salt thereof such as a hydrochloride, and a commercially available product can be used.

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Chloropyramine is 0.0001 to 10% by weight, preferably 0.01 to 10% by weight based on the total amount of the cosmetic or whitening agent of the present invention.
1.0 wt% can be blended. At a concentration of 0.0001% or less, a sufficient effect cannot be obtained, and at a concentration of 10% by weight or more, no enhancement of the effect is observed, which is uneconomical. The cosmetics and whitening agents of the present invention, within the range not impairing the effect of chloropyramine, oils and fats used in cosmetics and medicine, waxes,
Raw materials such as hydrocarbons, fatty acids, alcohols, esters, and surfactants can be blended. The cosmetic of the present invention can employ basic cosmetics such as creams, lotions, emulsions and packs, makeup cosmetics such as foundations and lipsticks, and bath forms, soaps, and other forms. The dosage form of the whitening agent of the present invention is a powder, a pill, a tablet, an injection, a suppository, an external preparation, etc., and is manufactured according to a usual formulation technique. The daily dose is
The dose can be 1 mg to 20 mg, preferably 2 mg to 10 mg, and can be administered in 2 to 3 divided doses.

[0006]

EXAMPLES Next, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto. The parts of the amounts shown in the examples are parts by weight.

Example-1 Lotion Formulation Formulation amount 1. Ethanol 5.0 parts 2. Methyl paraoxybenzoate 0.1 3. Polyoxyethylene (40) hydrogenated castor oil 0.1 4. Perfume proper amount 5. Purified water 10.0 6. Chloropyramine 0.1 7.1 , 3-Butylene glycol 3.0 8. Glycerin 2.0 9. Xanthan gum 0.02 10. Purified water 74.5 Manufacturing method: Components 1 to 5 and components 6 to 10 are uniformly dissolved, mixed and filtered to obtain a product.

Comparative Example-1 Conventional Lotion A conventional lotion was prepared by replacing chloropyramine with purified water in Example-1.

Example-2 Cream Formulation Amount 1. Liquid paraffin 6.5 parts 2. Vaseline 10.0 3. Stearic acid 4.0 4. Cetyl alcohol 3.0 5. Stearyl alcohol 1.0 6. Polyoxyethylene (25) monostearate 3.0 7. Sorbitan monostearate 2.5 8.1,3-Butylene glycol 5.0 9. Potassium hydroxide 0.1 10. Chloropyramine 1.0 11. Methyl paraoxybenzoate 0.2 12. Purified water 64.5 13. Perfume Suitable amount Production method: Oil phase components 1 to 7 and water phase After heating and dissolving components 8 to 12 at 70 to 75 ° C, respectively
Add 8 to 12 to emulsify, add and mix component 13 while cooling, and cool to 30 ° C to obtain a product.

Example-3 Emulsion formulation Formulation amount 1. Liquid paraffin 8.0 parts 2. Squalane 2.0 3. Stearyl alcohol 2.0 4. Sorbitan monooleate 2.5 5. Glycerin monostearate 2.3 6. Polyoxyethylene (10) sorbitan monooleate 0.8 7. Glycerin 6.0 8. Chloropyramine 0.1 9. Methyl paraoxybenzoate 0.2 10. Purified water 77.0 11. Perfume proper amount Production method: Oil phase components 1 to 6 and aqueous phase components 7 to 10 are heated and dissolved at 70 to 75 ° C, respectively. After that, the oil phase components 1 to 6 are added to the water phase components.
Add 7 to 10 to emulsify, add component 11 while mixing, mix and cool to 30 ° C to obtain a product.

Comparative Example-2 Conventional Emulsion In Example-3, the conventional emulsion was obtained by replacing chloropyramine with purified water.

Example-4 Pack Formulation Amount 1. Polyvinyl alcohol 12.0 parts 2. Ethyl alcohol 5.0 3.1,3-butylene glycol 8.0 4. Methyl paraoxybenzoate 0.2 5. Polyoxyethylene (40) hydrogenated castor oil 0.5 6. Chloropyramine 1.0 7. Citric acid 0.1 8. Sodium citrate 0.3 9. Perfume 0.1 10. Purified water 73.8 Manufacturing method: Dissolve each component uniformly to obtain a product.

Example-5 Foundation Formulation amount 1. Stearic acid 2.4 parts 2. Polyoxyethylene (20) sorbitan monostearate 1.0 3. Polyoxyethylene (20) cetyl ether 2.0 4. Cetyl alcohol 1.0 5. Liquid lanolin 2.0 6. Liquid paraffin 3.0 7. Isopropyl myristate 6.5 8. Butyl paraoxybenzoate 0.1 9. Purified water 58.2 10. Chloropyramine 0.01 11. Sodium carboxymethylcellulose 0.1 12. Bentonite 0.5 13. Propylene glycol 4.0 14. Triethanolamine 1.1 15 .Methyl paraoxybenzoate 0.2 16. Titanium oxide 8.0 17. Talc 4.0 18. Coloring pigment 5.0 19. Fragrance Suitable amount Production method: Components 10 to 13 and 15 are heated to 70 ° C. and swelled well. Ingredients 9 and 14 are dissolved in this to obtain an aqueous phase. Components 1 to 8 are dissolved by heating and kept at 80 ° C. to form an oil phase. The components 16 to 18 mixed well and passed through a pulverizer are added to the aqueous phase, and the mixture is stirred with a homomixer and kept at 75 ° C. The oil phase is added to the aqueous phase with stirring, cooled, and the component 19 is added at 45 ° C., and cooled with stirring to obtain a product.

Example-6 Bath agent Formulation amount 1. Sodium sulfate 43.0 parts 2. Sodium hydrogencarbonate 50.0 3. Chloropyramine 5.0 4. Yellow (202) (1) Appropriate amount 5. Perfume suitable amount Manufacturing method: Mix each component well And make it a product.

Example-7 Oily Ointment Formulation Amount 1. Purified lanolin 5.0 parts 2. Salix beeswax 5.0 3. Chloropyramine 0.1 4. White petrolatum 89.9 Production method: Mix the components well to obtain a product.

Comparative Example-3 Conventional oil-and-fat ointment In Example-7, the conventional oil-and-fat ointment was obtained by replacing chloropyramine with white petrolatum.

Example-8 Emulsion Ointment-1 Prescription Compounding amount 1. White petrolatum 25.0 2. Stearyl alcohol 22.0 3. Propylene glycol 12.0 4. Sodium lauryl sulfate 1.5 5. Ethyl paraoxybenzoate 0.025 6. Propyl paraoxybenzoate 0.015 7. Chloropyramine 0.2 8. Purified water 39.26 Production method: Oil phase components 1-2 and water phase components 3-8, respectively
After heating and melting at 70-75 ° C, the aqueous phase component 3
Add ~ 8 to emulsify and cool to 30 ° C to make the product.

Example-9 Emulsion Ointment-2 Prescription Compounding amount 1. Cholesterol 3.0 2. Stearyl alcohol 3.0 3. White beeswax 8.0 4. Chloropyramine 0.5 5. White petrolatum 85.5 Production method: 70-75 ° C. by mixing each component After melting by heating to
Cool to 30 ° C to obtain the product.

Example-10 Formulation of water-soluble ointment Blend amount 1. Polyethylene glycol 4000 49.9 2. Polyethylene glycol 400 49.9 3. Chloropyramine 0.2 Production method: Dissolve each component uniformly to obtain a product.

Example-11 Lotion formulation Formulation amount 1. Stearyl alcohol 2.5 2. Liquid paraffin 25.0 3. Sodium lauryl sulfate 1.0 4. Propylene glycol 12.0 5. Methyl paraoxybenzoate 0.025 6. Propyl paraoxybenzoate 0.025 7. Chloropyramine 0.5 8. Purified water 58.95 Manufacturing method: Oil phase components 1-2 and water phase components 3-8, respectively
After heating and melting at 70-75 ° C, the aqueous phase component 3
Add ~ 8 to emulsify and cool to 30 ° C to make the product.

Example-12 Tablet Formulation Compounding amount 1. Chloropyramine 10.0 parts 2. Corn starch 10.0 3. Purified sucrose 20.0 4. Carboxymethylcellulose calcium 10.0 5. Microcrystalline cellulose 35.0 6. Polyvinylpyrrolidone 5.0 7. Talc 2.0 Production method: Components 1 to 5 were mixed, and then an aqueous solution of component 6 was added as a binder and granulated by a conventional method. Component 7 was added as a lubricant to the mixture, and the mixture was tabletted into 100 mg tablets.

Example-13 Powder formulation Formulation amount 1. Chloropyramine 10 parts 2. Corn starch 40 3. Microcrystalline cellulose 50 Production method: The above components were mixed and made into a powder by a conventional method.

Example-14 Injectable formulation Formulation amount 1. Chloropyramine 10.0 parts 2. Polyoxyethylene (60) hydrogenated castor oil 37.0 3. Sesame oil 2.0 4. Sodium chloride 9.0 5. Propylene glycol 40.0 6. Phosphate buffer ( 0.1M, pH 6.0) 100.0 7. Distilled water 802.0 Manufacturing method: Mix components 1-3 and half amount of component 5 to about 8
Dissolve by heating at 0 ° C, and add component 6 and component 4 and component 5 to this.
Pre-dissolved ingredient 7 is heated to about 80 ℃ and added
It was an aqueous solution of ml. This aqueous solution was dispensed into a 1 ml ampoule, melted and sealed, and then heat sterilized.

[0024]

The whitening agent of the present invention has excellent melanin production inhibiting and whitening effects. Next, the effects of the whitening agent of the present invention will be described in more detail with reference to experimental examples.

Experimental Example-1 Melanin production inhibition test using B16 mouse melanoma 2 × 10 ⁴ cells of melanoma in the logarithmic growth phase were seeded in a φ60 mm dish, and chloropyramine hydrochloride was added so that the final concentrations were 2, 5 and 10 μM. Added Eagles' MEM (containing 10% FCS) was added, and the mixture was cultured at 37 ° C. under 5% CO ₂ . After 5 days of culturing, the cells were detached from the dish, and the cells were ultrasonically disrupted, 2N NaOH was added, the mixture was treated at 60 ° C for 2 hours, and OD475nm was measured with a spectrophotometer. In addition, the cell lysate after ultrasonic treatment was quantified for protein by the method of Lowry (J.Biol.Chem., 193,265-275,1951), and by comparing the amount of melanin per amount of protein, the effect of suppressing melanin production was confirmed. It was used as an index.
As is clear from the results shown in Table 1, chloropyramine exhibited a superior melanin production inhibitory action as compared with diphenhydramine and promethazine.

[0026]

[Table 1] Table 1 Inhibition of melanin production ──────────────────────────────────── Sample Sample concentration Melanin Amount Suppression rate (μM) (μg / mg protein) (%) ──────────────────────────────────── ─ Control 29.1 ± 0.5 Chloropyramine 2 14.1 ± 0.1 51.5 5 10.1 ± 0.2 65.3 10 9.8 ± 0.3 66.3 Diphenhydramine 10 20.1 ± 0.3 30.9 Promethazine 10 23.1 ± 0.8 20.6 ────────────────── ────────────────────

Experimental Example-2 Usage Test Using the lotion of Example-1, the emulsion of Example-3, the conventional lotion of Comparative Example-1 and the conventional emulsion of Comparative Example-2,
Each of 30 women (30 to 45 years old) was subjected to a usage test for one month. After use, the whitening effect was determined by a questionnaire survey on the improvement of skin spots, freckles, transparency and dullness. As a result, the cosmetics containing chloropyramine exhibited excellent whitening effect (Table 2, Table 3, Table 4, Table 5). Below margin

[0028]

[Table 2] Table 2 Whitening effect of the lotion of the present invention (number of questionnaire results) ─────────────────────────────── ── Lotion of the present invention (Example-1) Evaluation ─────────────────────── Very good Good Normal ──────── ──────────────────────── Skin stains and freckles 20 8 2 Transparency of the skin 20 7 3 Dullness of the skin 19 8 3 ───── ────────────────────────────

[0029]

[Table 3] Table 3 Whitening effect of conventional lotion (number of questionnaire results) ─────────────────────────────── ─ Conventional lotion (Comparative example-1) Evaluation ─────────────────────── Very good Good Normal ─────────── ────────────────────── Skin spots, freckles 1 7 22 Transparency of the skin 3 8 19 Dullness of the skin 2 9 21 ─────── ───────────────────────── Margins below

[0030]

[Table 4] Table 4 Whitening effect of the emulsion of the present invention (number of questionnaire results) ──────────────────────────────── -Emulsion of the present invention (Example-3) Evaluation ─────────────────────── Very good Good Normal ─────────── ────────────────────── Skin spots, freckles 21 7 2 Transparent skin 14 12 4 Dull skin 19 8 3 ─────── ─────────────────────────

[0031]

[Table 5] Table 5 Whitening effect of conventional emulsions (number of questionnaire results) ───────────────────────────────── Conventional emulsion (Comparative Example-2) Evaluation ─────────────────────── Very good Good Normal ───────────── ──────────────────── Skin spots and freckles 3 10 17 Transparent skin 4 8 18 Dull skin 3 7 20 ───────── ───────────────────────

Experimental Example-3 Clinical Example Example-7 was performed on four patients with pigmentation after sunburn inflammation.
The oily ointment shown in 1 was applied to the affected area once a day and observed for up to 3 months. At the same time, the conventional oil-based ointment of Comparative Example-3 was similarly tested. Judgment of effect:-: unchanged, +: thinned, ++: almost disappeared,
++++: Completely disappeared into 4 stages. No side effects were observed in all cases. As a result, as shown in Table 6, in the oily ointment of Example-7, the effect was recognized in 3 out of 4 cases. On the other hand, no effect was observed with the oily ointment of Comparative Example-3 (Table 7).

[0033]

[Table 6] Table 6 Whitening action of the oily ointment of the present invention ───────────────────────────────── Oily Ointment (Example-7) Subject Gender Age Skin Findings ──────────────────────────────── A Male 31 ++ Effective B Male 24 + Effective C Female 32 ++ Effective D Female 29-Ineffective ──────────────────────────────── ──

[0034]

[Table 7] Table 7 Whitening effect of conventional oil and fat ointment ──────────────────────────────── Conventional oil and fat Ointment (Comparative Example-3) Subject Gender Age Skin findings ──────────────────────────────── E Male 35 − No effect F Male 25-No effect G Female 29-No effect H Female 25-No effect ────────────────────────────────

The cream of Example-2, the pack of Example-4, the foundation of Example-5 and the bath agent of Example-6 were subjected to the usage test in the same manner as in Experimental Example-2. Showed the effect. Further, the emulsion ointment-1 of Example-8, the emulsion ointment-2 of Example-9, the water-soluble ointment of Example-10 and the lotion of Example-11 were clinically tested as in Experimental Example-3. When tested, it showed an excellent whitening effect. As shown above, chloropyramine exhibited an excellent melanin production inhibitory action, and the cosmetics and whitening agents containing the chloropyramine of the present invention exhibited an excellent whitening effect.

Claims (2)

[Claims] 1. A cosmetic comprising chloropyramine. 2. A whitening agent containing chloropyramine.