JP2018150266A - Skin external preparation for preventing and/or improving pimples - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin external preparation for preventing and/or improving pimples by combination use of three components of zinc sulfate, aluminum potassium sulfate and sodium hydrogen carbonate.SOLUTION: The combination use of three components of zinc sulfate, aluminum potassium sulfate and sodium hydrogen carbonate shows an excellent antibacterial effect on acne bacteria or Malassezia and excellent inhibitory effect on acne bacteria lipase or Malassezia lipase. Further, there is provided a skin external preparation for preventing and/or improving pimples comprising three components of zinc sulfate, aluminum potassium sulfate and sodium hydrogen carbonate which shows excellent prevention and improvement effect on pimples and has excellent safety and stability. Consequently, a skin external preparation comprising three components of zinc sulfate, aluminum potassium sulfate and sodium hydrogen carbonate is effective for preventing and/or improving pimples.SELECTED DRAWING: None

Description

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

  Acne is medically called acne vulgaris, and acne bacteria are involved in the inflammation. In recent years, it has been revealed that skin resident bacteria other than acne bacteria such as Malassezia are involved in acne inflammation (Non-patent Document 1). The lipase produced by Acne or Malassezia degrades 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 Acne or Malassezia and to inhibit the activity of lipase produced by these microorganisms.

  Therefore, many antibacterial agents and lipase inhibitors against acne are used for the purpose of preventing and / or improving acne (Patent Documents 1 and 2). Many antibacterial agents and lipase inhibitors against malassezia have been reported (Patent Documents 2 and 3).

  In addition, it has been reported that hot spring ingredients also have acne prevention and / or improvement effects (Patent Document 4).

JP2014-062059 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 ingredients on acne are not always sufficient, and the development of new ingredients with high effects 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 three components of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate has excellent antibacterial properties against acne and malassezia, acne lipase and It has been found that it has an excellent inhibitory effect on maraceti alipase. Furthermore, it discovered that the skin external preparation containing three components of zinc sulfate, potassium aluminum sulfate, and sodium hydrogencarbonate had the prevention and / or improvement effect with respect to acne, and came to complete this invention.

Zinc sulfate used in the present invention is a component of a sulfate spring and is represented by ZnSO ₄ . A manufacturing method is not specifically limited.

The 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 potash alum. A manufacturing method is not specifically limited.

Sodium bicarbonate 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. A manufacturing method is not specifically 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 the amount is less than 0.01% by weight, it is difficult to obtain a sufficient effect.

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

  The content of sodium bicarbonate in the external preparation for skin (excluding bath preparation) in the present invention is preferably 0.01 to 1% by weight. If the amount is less than 0.01% by weight, it is difficult to obtain a sufficient effect.

  In the external preparation for skin of the present invention, fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, which are components used for normal external preparations for skin, within a range that does not impair the effect. It can also contain components such as agents, metal soaps, preservatives, fragrances, humectants, powders, UV absorbers, thickeners, dyes, antioxidants, whitening agents, chelating agents and the like.

  In the present invention, zinc sulfate, aluminum potassium sulfate, and sodium hydrogen carbonate can be used for cosmetics, quasi drugs, and pharmaceuticals. Examples of the dosage form include skin lotions, creams, emulsions, and gels. , Aerosol agents, essences, packs, cleaning agents, bath preparations, foundations, powders, ointments and the like.

  The combined use of three components of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate showed excellent antibacterial activity against acne and malassezia and excellent inhibitory effect against acne lipase and maraceti alipase. Moreover, the skin external preparation containing the three components of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate showed excellent prevention and / or improvement effects against acne.

  Next, in order to describe the present invention in detail, examples of formulation and experimental examples of the present invention will be given as examples, but the present invention is not limited thereto. The part of the content shown in the examples indicates parts by weight.

Formulation Example 1 Cream [Prescription] Content 1. Zinc sulfate 0.03 parts Potassium aluminum sulfate 0.05
3. Sodium bicarbonate 0.1
4). Squalane 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 (20E.O.) 3.0
10. Behenyl alcohol 1.5
11. Glycerol monostearate2.5
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] Components 4 to 11 are heated and dissolved and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 to 3 and 13 to 16 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 12 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 2 Lotion [Prescription] Content 1. Zinc sulfate 0.02 parts Potassium aluminum sulfate 0.1
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 (40E.O.) 0.1
12 Fragrance 0.1
13. Purified water 84.25
[Production Method] Components 1 to 8 and 13 and Components 9 to 12 are uniformly dissolved, mixed and filtered to obtain a product.

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

Formulation Example 3 Emulsion [Prescription] Content 1. Zinc sulfate 0.03 parts Potassium aluminum sulfate 0.05
3. Sodium bicarbonate 0.1
4). Squalane 5.0
5. Olive oil 5.0
6). Jojoba oil 5.0
7). Cetanol 1.5
8). Glycerol monostearate 2.0
9. Polyoxyethylene cetyl ether (20E.O.) 3.0
10. Polyoxyethylene sorbitan monooleate 2.0
(20 EO)
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] Components 4 to 10 are heated and dissolved, mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 to 3 and 12 to 15 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring. The component 11 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 4 Gel [Prescription] Content 1. Zinc sulfate 0.03 parts Potassium aluminum sulfate 0.05
3. Sodium bicarbonate 0.1
4). Ethanol 5.0
5. Methyl paraoxybenzoate 0.1
6). Polyoxyethylene hydrogenated castor oil (60 EO) 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] Components 4 to 7 and components 1 to 3 and 8 to 13 are uniformly dissolved and mixed to obtain a product.

Formulation Example 5 Pack [Prescription] Content 1. Zinc sulfate 0.03 parts Potassium aluminum sulfate 0.05
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 (20 EO) 0.5
9. Citric acid 0.1
10. Sodium citrate 0.3
11. Fragrance 0.1
12 Purified water 73.62
[Production Method] Components 1 to 12 are uniformly dissolved to obtain a product.

Formulation Example 6 Foundation [Prescription] Content 1. Zinc sulfate 0.02 parts Potassium aluminum sulfate 0.1
3. Sodium bicarbonate 0.2
4). Sodium carbonate 0.1
5. Stearic acid 2.4
6). Polyoxyethylene sorbitan monostearate 1.0
(20 EO)
7). Polyoxyethylene cetyl ether (20E.O.) 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 carboxymethylcellulose 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] Components 5 to 12 are dissolved by heating and kept at 80 ° C to obtain an oil phase. Swell component 13 well in component 23, then add components 1-4 and 14-17 and mix uniformly. To this, components 18 to 21 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 oily phase is added to the aqueous phase while stirring, cooled, component 22 is added at 45 ° C., and cooled to 30 ° C. with stirring to give a product.

Formulation Example 7 Bath Agent [Prescription] Content 1. Zinc sulfate 5.0 parts2. Potassium aluminum sulfate 5.0
3. Sodium bicarbonate 45.0
4). Yellow No. 202 (1) 0.1
5. Fragrance 0.1
6). Anhydrous sodium sulfate 44.8
[Production Method] Components 1 to 6 are uniformly mixed to obtain a product.

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

Experimental Example 1 Antibacterial activity test According to the standard plate dilution method of the Japanese Society of Chemotherapy, the minimum of zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate against Acne bacteria (Propionibacterium acnes JCM 6425) and Malassezia (Malazezia globosa NBRC 101597) The growth inhibitory concentration (MIC, μg / mL) was measured. That is, using the culture medium which added each component so that it might become 16-16000 microgram / mL (common ratio 2), the growth property of the acne bacteria and the Malassezia was examined. As the medium, modified GAM agar medium (Nissui Pharmaceutical) was used for acne, and Leeming & Notman agar medium (J Clin Microbiol, Vol. 25, PP. 2017-2019, 1987) was used for malassezia. Acne bacteria were 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 acne bacteria.

  The MIC for acne bacteria was 500 μg / mL (No. 1) for zinc sulfate alone, 8000 μg / mL (No. 2) for potassium aluminum sulfate alone, and 16000 μg / mL (No. 3) for sodium bicarbonate 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 the three-component combination, zinc sulfate: 250 μg / mL, potassium aluminum sulfate: 500 μg / mL, sodium hydrogen carbonate: 1000 μg (No. 8), zinc sulfate: 125 μg / mL, 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 Malassezia 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 bicarbonate 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 three-component combination, 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, potassium aluminum sulfate: 125 μg / mL, and sodium bicarbonate: 250 μg (No. 10), and a synergistic effect was observed.

Experimental Example 2 Lipase Activity Inhibition Test Zinc sulfate, potassium aluminum sulfate and carbonate for Acne (Propionibacterium acnes JCM 6425) and Malassezia (Malassezia globosa NBRC 101597) according to the literature (Hichikaikai, 115, 2381-2388, 2005) The inhibitory effect of sodium hydrogen lipase activity was measured. For acne bacteria, brain heart infusion medium (Eiken Chemical Co., Ltd.) was used, and the culture cultured at 35 ° C. for 48 hours under anaerobic conditions was centrifuged at 15000 rpm for 10 minutes. It was. For malassezia, a culture cultured for 72 hours at 32.5 ° C. using Leeming & Notman ager medium was dispersed in Mclvine buffer (pH 5.0) to obtain a maraceti alipase solution. After mixing 50 μL of Mclvaine buffer (Acne bacteria: pH 7.4, Malassezia: pH 5.0) containing 4.0% by weight of zinc sulfate, potassium aluminum sulfate or sodium bicarbonate in a 96-well plate, 35 Incubated for 30 minutes at ° C. Next, 100 μL of Mclvaine buffer containing 0.01 mM 4-methylumbelliferone oleate was added and incubated at 35 ° C. for 30 minutes. Thereafter, the fluorescence intensity of Acne lipase was measured with a microplate reader (Ex: 320 nm, Em: 450 nm). For maraceti alipase, centrifugation was performed at 2000 rpm for 10 minutes, and 100 μL of the obtained supernatant was transferred to a new 96-well plate, and the fluorescence intensity was measured. The inhibition rate (%) of lipase activity was determined with the fluorescence intensity when the sample was not added as 100.

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

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

  Table 4 shows the inhibitory effects of each component on malachite alipase.

  When the three components were used in combination, the malase thiolipase activity inhibition rate increased synergistically.

Experimental Example 3 Acne Prevention and / or Improvement Effects 70 women suffering from acne using the lotion of Example 1 and the lotions A to F of Comparative Example 1 (20 to 44 years old, 10 per each lotion) A one-month use test was conducted on the subjects. After use, the prevention and improvement of acne were determined by questionnaire survey.

  The results are shown in Table 5.

  From the results of Table 5, zinc sulfate, potassium aluminum sulfate and hydrogen carbonate compared to lotions A to F of Comparative Example 1 using either one of zinc sulfate, potassium aluminum sulfate or sodium hydrogen carbonate, or two in combination. The lotion of Example 2 using three of sodium in combination showed excellent acne prevention and improvement effects. In addition, there was no skin problem during the test period, and there was no problem in safety.

  As a result of conducting a use test on the skin external preparations obtained in Examples 1 and 3 to 7 as well, all of them showed sufficient acne prevention and / or improvement effects. In addition, there was no skin trouble during the test period, and there was no problem in safety.

  From the above, the combined use of the three components of zinc sulfate, potassium aluminum sulfate and sodium bicarbonate of the present invention has a synergistic excellent antibacterial effect and lipase activity inhibitory effect against acne and malassezia, which are acne-causing bacteria. Indicated. Moreover, the skin external preparation which used together three components of zinc sulfate, potassium aluminum sulfate, and sodium hydrogencarbonate showed the prevention and / or improvement effect of the outstanding acne.

The topical skin preparation containing zinc sulfate, potassium aluminum sulfate, and sodium hydrogen carbonate according to the present invention can be used for cosmetics, quasi drugs, and pharmaceuticals for the purpose of preventing and / or improving acne. is there.

Claims (3)

An antibacterial agent against Acne and / or Malassezia, comprising zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate. An activity inhibitor against Acne lipase and / or Maraceti alipase, characterized by containing zinc sulfate, potassium aluminum sulfate and sodium bicarbonate. A skin external preparation for preventing and / or improving acne, characterized by containing zinc sulfate, potassium aluminum sulfate and sodium hydrogen carbonate.