JP6840324B2 - Topical skin for acne prevention and / or improvement - Google Patents

Description

The present invention is a skin external preparation for preventing and / or improving acne, which comprises zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate.

Acne is medically called acne vulgaris, and P. acnes is involved in its inflammation. In recent years, it has become clear that skin flora other than P. acnes, such as Malassezia, is also involved in acne inflammation (Non-Patent Document 1). Lipase produced by P. acnes and Malassezia decomposes sebum, and the fatty acids generated thereby cause inflammation (Non-Patent Documents 2 and 3). That is, in order to prevent and / or improve acne inflammation, it is important to suppress the growth of P. acnes and Malassezia and to inhibit the activity of lipase produced by these microorganisms.

Therefore, antibacterial agents and lipase inhibitors against P. acnes are often used for the purpose of preventing and / or improving acne (Patent Documents 1 and 2). In addition, many antibacterial agents and lipase inhibitors against Malassezia have been reported (Patent Documents 2 and 3).

It has also been reported that hot spring ingredients also have an effect of preventing and / or improving acne (Patent Document 4).

JP-A-2014-062059 Special table 2012-136447 Special table 2013-249293 Special table 2002-326942

J Dermatol, Vol. 43, PP. 906-911 (2016) Eur J Dermatol, Vol. 14, PP. 4-12 (2004) J Med Vet Mycol, Vol. 31, PP. 77-85 (1993)

However, the effects of these components on acne are not always sufficient, and the development of highly effective new components has been desired.

As a result of diligent research aimed at solving the above problems, the present inventors have found that the combined use of the three components of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate has excellent antibacterial properties against P. acnes and Malassezia, as well as P. acnes lipase and It was found to have an excellent inhibitory effect on malassezia lipase. Furthermore, they have found that an external preparation for skin containing three components of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate has a preventive and / or ameliorating effect on acne, and have completed the present invention.

Zinc sulfate used in the present invention is a component of a sulfate spring and is represented by _{ZnSO 4.} The manufacturing method is not particularly limited.

Potassium aluminum sulfate used in the present invention is a component of alum spring and is represented by _{AlK (SO 4} ) _2. Also called potassium alum or potassium alum. The manufacturing method is not particularly limited.

The sodium hydrogen carbonate used in the present invention is a component of a bicarbonate spring and is represented by _{NaHCO 3.} Also called sodium bicarbonate, sodium bicarbonate, or baking soda. The manufacturing method is not particularly limited.

The content of zinc sulfate in the external preparation for skin (excluding bath preparation) in the present invention is preferably 0.01 to 1% by weight. If it is less than 0.01% by weight, it is difficult to obtain a sufficient effect, and if it exceeds 1% by weight, the enhancement of the effect is small and uneconomical.

The content of potassium aluminum sulfate in the external preparation for skin (excluding bath preparation) in the present invention is preferably 0.01 to 1% by weight. If it is less than 0.01% by weight, it is difficult to obtain a sufficient effect, and if it exceeds 1% by weight, the enhancement of the effect is small and uneconomical.

The content of sodium hydrogen carbonate in the external preparation for skin (excluding bath preparation) in the present invention is preferably 0.01 to 1% by weight. If it is less than 0.01% by weight, it is difficult to obtain a sufficient effect, and if it exceeds 1% by weight, the enhancement of the effect is small and uneconomical.

The skin external preparation of the present invention includes fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, and surfactants, which are components used in ordinary skin external preparations, as long as the effects are not impaired. It can also contain components such as agents, metal soaps, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments, antioxidants, whitening agents, chelating agents and the like.

In the present invention, zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate can be used for any of cosmetics, quasi-drugs and pharmaceuticals, and the dosage forms thereof include, for example, cosmetics, creams, emulsions and gels. , Aerosols, essences, packs, cleaning agents, bathing agents, foundations, dusting powders, ointments and the like.

The combined use of the three components of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate showed excellent antibacterial activity against P. acnes and Malassezia and excellent inhibitory effect against P. acnes lipase and Malassezia lipase. In addition, the external preparation for skin containing the three components of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate showed an excellent preventive and / or ameliorating effect on acne.

Next, in order to explain the present invention in detail, a formulation example and an experimental example of the present invention will be given as examples, but the present invention is not limited thereto. The content part shown in the examples means a weight part.

Prescription example 1 Cream [prescription] Content 1. Zinc sulfate 0.03 part 2. Potassium aluminum sulphate 0.05
3. 3. Sodium bicarbonate 0.1
4. Squalene 5.5
5. Olive oil 3.0
6. Stearic acid 2.0
7. Beeswax 2.0
8. Octyldodecyl myristate 3.5
9. Polyoxyethylene cetyl ether (20EO) 3.0
10. Behenyl alcohol 1.5
11. Glycerin monostearate 2.5
12. Fragrance 0.1
13.1,3-butylene glycol 8.5
14. Ethyl paraoxybenzoate 0.05
15. Methyl paraoxybenzoate 0.2
16. Purified water 67.97
[Manufacturing method] Ingredients 4 to 11 are heated, dissolved and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 to 3 and 13 to 16 are heated and dissolved and mixed, and kept at 75 ° C. to prepare an aqueous phase. An aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring, component 12 is added at 45 ° C., and the mixture is further cooled to 30 ° C. to obtain a product.

Prescription example 2 Toner [prescription] Content 1. Zinc sulfate 0.02 part 2. Potassium aluminum sulphate 0.1
3. 3. Sodium bicarbonate 0.2
4.1,3-butylene glycol 8.0
5. Glycerin 2.0
6. Xanthan gum 0.02
7. Citric acid 0.01
8. Sodium citrate 0.1
9. Ethanol 5.0
10. Methyl paraoxybenzoate 0.1
11. Polyoxyethylene hydrogenated castor oil (40EO) 0.1
12. Fragrance 0.1
13. Purified water 84.25
[Manufacturing method] Components 1 to 8 and 13 and components 9 to 12 are uniformly dissolved, and both are mixed and filtered to obtain a product.

Comparative Example 1 Toners A to F
In Formulation Example 2, one or two of the components 1 to 3 were contained, and the rest was replaced with purified water as cosmetics A to F.
Toner A: Contains only zinc sulfate (component 1) Toner B: Contains only potassium aluminum sulfate (component 2) Toner C: Contains only sodium hydrogen carbonate (component 3) Toner D: Contains zinc sulfate (component 1) and sulfate Contains only aluminum potassium (component 2) Toner E: Contains only zinc sulfate (component 1) and sodium hydrogen carbonate (component 3) Toner F: Contains only potassium aluminum sulfate (component 2) and sodium hydrogen carbonate (component 3)

Prescription example 3 Emulsion [prescription] Content 1. Zinc sulfate 0.03 part 2. Potassium aluminum sulphate 0.05
3. 3. Sodium bicarbonate 0.1
4. Squalene 5.0
5. Olive oil 5.0
6. Jojoba oil 5.0
7. Cetanol 1.5
8. Glycerin monostearate 2.0
9. Polyoxyethylene cetyl ether (20EO) 3.0
10. Polyoxyethylene sorbitan monooleate 2.0
(20EO)
11. Fragrance 0.1
12. Propylene glycol 1.0
13. Glycerin 2.0
14. Methyl paraoxybenzoate 0.2
15. Purified water 73.02
[Manufacturing method] Ingredients 4 to 10 are melted by heating and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 to 3 and 12 to 15 are heated and dissolved and mixed to prepare an aqueous phase at 75 ° C. An aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring, component 11 is added at 45 ° C., and the mixture is further cooled to 30 ° C. to obtain a product.

Prescription example 4 Gel [prescription] Content 1. Zinc sulfate 0.03 part 2. Potassium aluminum sulphate 0.05
3. 3. Sodium bicarbonate 0.1
4. Ethanol 5.0
5. Methyl paraoxybenzoate 0.1
6. Polyoxyethylene hydrogenated castor oil (60EO) 0.1
7. Fragrance 0.1
8.1,3-butylene glycol 5.0
9. Glycerin 5.0
10. Xanthan gum 0.1
11. Carboxyvinyl polymer 0.2
12. Potassium hydroxide 0.2
13. Purified water 84.02
[Manufacturing method] Ingredients 4 to 7 and components 1 to 3 and 8 to 13 are uniformly dissolved, and the two are mixed to prepare a product.

Prescription example 5 pack [prescription] Content 1. Zinc sulfate 0.03 part 2. Potassium aluminum sulphate 0.05
3. 3. Sodium bicarbonate 0.1
4. Polyvinyl alcohol 12.0
5. Ethanol 5.0
6.1,3-butylene glycol 8.0
7. Methyl paraoxybenzoate 0.2
8. Polyoxyethylene hydrogenated castor oil (20EO) 0.5
9. Citric acid 0.1
10. Sodium citrate 0.3
11. Fragrance 0.1
12. Purified water 73.62
[Manufacturing method] Ingredients 1 to 12 are uniformly dissolved to prepare a product.

Prescription Example 6 Foundation [Prescription] Content 1. Zinc sulfate 0.02 part 2. Potassium aluminum sulphate 0.1
3. 3. Sodium bicarbonate 0.2
4. Sodium carbonate 0.1
5. Stearic acid 2.4
6. Polyoxyethylene sorbitan monostearate 1.0
(20EO)
7. Polyoxyethylene cetyl ether (20EO) 2.0
8. Cetanol 1.0
9. Liquid lanolin 2.0
10. Liquid paraffin 3.0
11. Isopropyl myristate 6.5
12. Butyl paraoxybenzoate 0.1
13. Sodium Carboxymethyl Cellulose 0.1
14. Bentonite 0.5
15. Propylene glycol 4.0
16. Triethanolamine 1.1
17. Methyl paraoxybenzoate 0.2
18. Titanium dioxide 8.0
19. Talc 4.0
20. Bengala 1.0
21. Yellow iron oxide 2.0
22. Fragrance 0.1
23. Purified water 60.58
[Manufacturing method] Ingredients 5 to 12 are melted by heating and kept at 80 ° C. to prepare an oil phase. The component 13 is well swollen to the component 23, and then the components 1 to 4 and 14 to 17 are added and mixed uniformly. Ingredients 18 to 21 pulverized and mixed by a pulverizer are added thereto, and the mixture is stirred with a homomixer and kept at 75 ° C. to prepare an aqueous phase. The oil phase is added to the aqueous phase while stirring, and the mixture is cooled. Ingredient 22 is added at 45 ° C. and cooled to 30 ° C. while stirring to obtain a product.

Prescription Example 7 Bathing agent [Prescription] Content 1. Zinc sulfate 5.0 parts 2. Potassium aluminum sulphate 5.0
3. 3. Sodium bicarbonate 45.0
4. Yellow No. 202 (1) 0.1
5. Fragrance 0.1
6. Anhydrous sodium sulfate 44.8
[Manufacturing method] Ingredients 1 to 6 are uniformly mixed to prepare a product.

Next, in order to explain the effect of the present invention in detail, an experimental example will be given.

Experimental Example 1 Antibacterial activity test The minimum amount of zinc sulfate, potassium aluminum sulfate, and sodium hydrogen carbonate against P. acnes (Propioniva bacterium acnes JCM 6425) and Malassezia globosa NBRC 101597 according to the standard method of the Japan Society of Chemotherapy. The growth inhibitory concentration (MIC, μg / mL) was measured. That is, the growth of P. acnes and Malassezia was examined using a medium in which each component was added so as to be 16 to 16000 μg / mL (common ratio 2). As the medium, modified GAM agar medium (Nissui Pharmaceutical Co., Ltd.) was used for P. acnes, and Leeming & Notman agar medium (J Clin Microbiol, Vol. 25, PP. 2017-2019, 1987) was used for Maracetia. P. acnes was cultured at 35 ° C. under anaerobic conditions for 5 days. Malassezia was cultured at 32.5 ° C. for 12 days.

Table 1 shows the antibacterial properties of each component against P. acnes.

The MIC against acne bacteria was 500 μg / mL (No. 1) with zinc sulfate alone, 8000 μg / mL (No. 2) with potassium aluminum sulfate alone, and 16000 μg / mL (No. 3) with sodium hydrogen carbonate alone. In the case of two-component combination, zinc sulfate: 250 μg / mL and potassium aluminum sulfate: 4000 μg / mL (No. 4), zinc sulfate: 250 μg / mL and sodium hydrogen carbonate: 8000 μg / mL (No. 5), zinc sulfate: 125 μg / ML and potassium aluminum sulfate: 8000 μg / mL (No. 6), zinc sulfate: 125 μg / mL and sodium hydrogen carbonate: 16000 μg / mL (No. 7), and the effects were additive. In the case of combined use of 3 components, zinc sulfate: 250 μg / mL, potassium aluminum sulfate: 500 μg / mL and sodium hydrogen carbonate: 1000 μg (No. 8), zinc sulfate: 125 μg / mL and potassium aluminum sulfate: 1000 μg / mL and sodium hydrogen carbonate. : 2000 μg (No. 9), zinc sulfate: 63 μg / mL, aluminum potassium sulfate: 2000 μg / mL and sodium hydrogen carbonate: 4000 μg (No. 10), and a synergistic effect was observed.

Table 2 shows the antibacterial properties of each component against Malassezia.

The MIC for malacetia was 125 μg / mL (No. 1) for zinc sulfate alone, 500 μg / mL (No. 2) for potassium aluminum sulfate alone, and 1000 μg / mL (No. 3) for sodium hydrogen carbonate alone. In the case of two-component combination, zinc sulfate: 63 μg / mL and potassium aluminum sulfate: 250 μg / mL (No. 4), zinc sulfate: 63 μg / mL and sodium hydrogen carbonate: 500 μg / mL (No. 5), zinc sulfate: 32 μg / ML and potassium aluminum sulfate: 500 μg / mL (No. 6), zinc sulfate: 32 μg / mL and sodium hydrogen carbonate: 1000 μg / mL (No. 7), and the effects were additive. In the case of combined use of three components, zinc sulfate: 63 μg / mL, potassium aluminum sulfate: 32 μg / mL, sodium hydrogen carbonate: 63 μg (No. 8), zinc sulfate: 32 μg / mL, potassium aluminum sulfate: 63 μg / mL, and sodium hydrogen carbonate. : 125 μg (No. 9), zinc sulfate: 16 μg / mL, aluminum potassium sulfate: 125 μg / mL, and sodium hydrogen carbonate: 250 μg (No. 10), and a synergistic effect was observed.

Experimental Example 2 Lipase activity inhibition test According to the literature (Journal of the Japan Skin Society, 115, 2381-2388, 2005), zinc sulfate, potassium aluminum sulfate and carbon dioxide against P. acnes (Propionibacterium acnes JCM 6425) and Malassezia globosa NBRC 101597. The inhibitory effect of sodium hydrogen on lipase activity was measured. For P. acnes, using Brainheart infusion medium (Eiken Chemical), the culture cultured at 35 ° C. for 48 hours under anaerobic conditions was centrifuged at 15,000 rpm for 10 minutes, and the obtained supernatant was obtained as a lipase solution for P. acnes. And said. For Malassezia, a culture cultured at 32.5 ° C. for 72 hours using Leeming & Notman age medium was dispersed in Mclvaine buffer (pH 5.0) to prepare a Malassezia lipase solution. After mixing 50 μL of Mclvaine buffer (P. acnes: pH 7.4, Malassezia: pH 5.0) containing 4.0% by weight of zinc sulfate, potassium aluminum sulfate or sodium hydrogen carbonate in a 96-well well plate, 35 Incubated at ° C for 30 minutes. Next, 100 μL of Mclvaine buffer containing 0.01 mM 4-methylumbelliferone oleate was added, and the mixture was incubated at 35 ° C. for 30 minutes. Then, for P. acnes lipase, the fluorescence intensity was measured with a microplate reader (Ex: 320 nm, Em: 450 nm). Malassezia lipase was centrifuged at 2000 rpm for 10 minutes, 100 μL of the obtained supernatant was transferred to a new 96-well well plate, and the fluorescence intensity was measured. The lipase activity inhibition rate (%) was determined with the fluorescence intensity when no sample was added as 100.

Table 3 shows the inhibitory effect of each component on P. acnes lipase.

When the three components were used in combination, the inhibition rate of P. acnes lipase activity increased synergistically.

Table 4 shows the inhibitory effect of each component on malassezia furfurase.

When the three components were used in combination, the malassezia lipase activity inhibition rate increased synergistically.

Experimental Example 3 Acne Prevention and / or Improvement Effect Using the lotion of Example 1 and the lotions A to F of Comparative Example 1, 70 women (20 to 44 years old, 10 per lotion) suffering from acne. Was used for one month. After use, a questionnaire survey was conducted to determine the prevention and improvement of acne.

The results are shown in Table 5.

From the results in Table 5, zinc sulfate, potassium aluminum sulfate, and hydrogen carbonate were compared with the lotions A to F of Comparative Example 1 in which either one or two of zinc sulfate, potassium aluminum sulfate, or sodium hydrogen carbonate was used in combination. The lotion of Example 2 in which three sodiums were used in combination showed an excellent preventive and ameliorating effect on acne. There was no skin trouble during the test period, and there was no problem in terms of safety.

As a result of the same use test for the external preparations for skin obtained in Examples 1 and 3 to 7, all of them showed a sufficient effect of preventing and / or improving acne. In addition, there was no skin trouble during the test period, and there was no problem in terms of safety.

Based on the above, the combined use of the three components of zinc sulfate, potassium aluminum sulfate, and sodium hydrogen carbonate of the present invention provides excellent synergistic antibacterial effect and lipase activity inhibitory effect against acne bacteria and Malassezia, which are acne-causing bacteria. Indicated. In addition, the external preparation for skin in which the three components of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate were used in combination showed an excellent effect of preventing and / or improving acne.

The external preparation for skin characterized by containing zinc sulfate, potassium aluminum sulfate, and sodium hydrogen carbonate of the present invention can be used in cosmetics, quasi-drugs, and pharmaceuticals for the purpose of preventing and / or ameliorating acne. is there.

Claims (3)

Acne bacteria containing 0.0063 to 0.025% by weight of zinc sulfate, 0.05 to 0.2% by weight of potassium aluminum sulfate , and 0.1 to 0.4% by weight of sodium hydrogen carbonate. Antibacterial agent against . 0.0016 to 0.063 wt% of zinc sulfate, for Malassezia, characterized in that it contains 0.0032 to 0.0125% by weight of aluminum potassium sulfate, and sodium bicarbonate 0.0063 to 0.025 wt% Antibacterial agent . 0.0016 to 0.063 wt% of zinc sulfate, acne prevention, characterized in that it contains from 0.0063 to 0.4 wt% from 0.0032 to 0.2 wt%, and sodium bicarbonate potassium aluminum sulfate And / or skin external preparation for improvement.