JP2002114670A - Antimicrobial skin care preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a skin care preparation having excellent antimicrobial activities against Trichophyton, Propionibacterium acnes, Pityrosporum ovale, or the like, and having low irritation. SOLUTION: This skin care preparation is obtained by formulating one or more kinds selected from the group consisting of a photosensitizer 201 (pionin), undecylenic acid, its salts and derivatives, and hinokitiol, its salts and derivatives, with a skin care preparation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin having excellent antibacterial properties and low irritation to skin. More specifically, a high antibacterial property is obtained by mixing Photosensitizer No. 201 (Pionin) with one or more selected from the group consisting of undecylenic acid, salts and derivatives thereof, and hinokitiol, salts and derivatives thereof. It relates to a hypoallergenic skin external preparation.

[0002]

2. Description of the Related Art Antibacterial agents for disinfecting bacteria and fungi on the skin surface and for bacteriostatic purposes are used in the fields of cosmetics, quasi-drugs, and pharmaceuticals, and include medicinal solid or liquid soaps, athlete's foot drugs, and acne prevention. It is widely used as an agent, an antidandruff agent, an antiperspirant, a hand sanitizer, and the like.

Here, athlete's foot is Trichophyton
Due to the infection of mentagrophytes ( Trichophytonmentagrophytes ) and acne, the acne bacteria ( Propionibacterium acnes,
It is known that dandruff of P. ium acnes is induced by the proliferation of Pityrosporum ovale , which is present on the scalp. Therefore, if the Trichophyton, Acne and Dandruff can be efficiently killed, athlete's foot, acne and dandruff can be effectively prevented.

[0004] However, sulfur, photosensitive element 201,
Antibacterial components such as undecylenic acid, hinokitiol, and berberine exhibit extremely high antibacterial activity against the above-mentioned bacteria and fungi in test tubes, but do not actually cause skin irritation to external skin preparations such as creams and ointments. Even when the amount was blended and used for treatment, antibacterial properties as expected were not obtained, and most of them did not exhibit a therapeutic effect. Conversely, if sufficient antibacterial properties are to be obtained, skin irritation will occur, and in people with sensitive skin, people with diseases or inflammation due to athlete's foot or acne, etc., inflammation or rough hands due to skin irritation will easily occur. Had the disadvantage that Therefore, development of an antibacterial agent that has less irritation to the skin and has a sufficient antibacterial action has been desired.

[0005]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide an excellent antibacterial activity against bacteria such as Trichophyton, acne and dandruff, and fungi, athlete's foot, acne, dandruff and the like produced by these bacteria and fungi. An object of the present invention is to provide a highly safe and less irritating antibacterial skin external preparation which can prevent the occurrence of inflammation caused by the skin.

[0006]

As a result of various investigations to solve the above-mentioned problems, as a result, Photosensitizer No. 201 (Pionin) was obtained.
And 1 selected from the group consisting of undecylenic acid, salts and derivatives thereof, and hinokitiol, salts and derivatives thereof
The use of a skin external preparation comprising two or more species or two or more species synergistically enhances the antibacterial activity against bacteria such as Trichophyton, acne, dandruff and the like, and superficial skin using these as causative bacteria. It has been found that infectious diseases and the like are promptly improved, and the present invention has been completed.

[0007] That is, the present invention provides an excellent antibacterial composition comprising Photosensitizer No. 201 and one or more selected from the group consisting of undecylenic acid, salts and derivatives thereof, and hinokitiol, salts and derivatives thereof. It is intended to obtain an external preparation for skin having properties and low irritation to the skin.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, Photosensitive Element No. 201 (Pionin) is blended with one or more selected from the group consisting of undecylenic acid, salts and derivatives thereof, and hinokitiol, salts and derivatives thereof. It is a skin external preparation.

The salts and derivatives of undecylenic acid used in the present invention include, for example, sodium undecylenate, potassium undecylenate, magnesium undecylenate,
Undecylenic soaps such as calcium undecylenate and zinc undecylenate, methyl undecylenate, ethyl undecylenate, propyl undecylenate, isopropyl undecylenate, butyl undecylenate, pentyl undecylenate, hexyl undecylenate, heptyl undecylenate, octyl undecylenate, undecylenate, undecylenate Alkyl or alkenyl or aryl esters of undecylenic acid such as benzyl or allyl undecylenate, glycerin monoundecylenic ester, glycerin diundecylenic ester, ethylene glycol monoundecylenate, propylene glycol monoundecylenate, ethylene glycol diundecylenate, diundecylenic acid Propylene glycol, sorbitan undecylenate, trehalose Undecylenic acid polyhydric alcohol esters such as undecylenic acid ester, diglycerin undecylenic acid ester, polyglycerin undecylenic acid ester, sucrose undecylenic acid ester, polyethylene glycol undecylenic acid ester, polypropylene glycol undecylenic acid ester, undecylenic acid monoethanolamide, undecylenic acid Alkanolamides of undecylenic acid such as diethanolamide, triethanolamide of undecylenic acid and aminoethylethanolamide of undecylenic acid, amides of undecylenic acid,
Undecylenic acid (alkyl) amides such as bis-undecylenic acid amide, undecylenic acid-N-methylamide, undecylenic acid-N-ethylamide, bis-undecylenic ethylenediamide, bis-undecylenic acid propylenediamide, bis-undecylenic acid Unalkylated polyalkylene polyamides such as diethylene triamide; neomycin undecylenate;

The hinokitiol salts and derivatives used in the present invention include hinokitiol sodium salt, hinokitiol potassium salt, hinokitiol magnesium salt, hinokitiol calcium salt, hinokitiol zinc complex, hinokitiol copper complex, hinokitiol ammonium salt, hinokitiol-2-amino-2. -Ethyl-1,3-propanediol salt, hinokitiol triethanolamine salt, hinokitiol lysine salt, hinokitiol arginine salt, hinokitiol histidine salt, hinokitiol piperidine salt, hinokitiol piperazine salt, hinokitiol morphylin salt, and acetyl hinokitiol.

Here, the photosensitive element 201 (Pionin)
An external preparation for skin composed of a combination of one or more selected from undecylenic acid, salts and derivatives thereof, and one or more selected from hinokitiol, salts and derivatives thereof, includes photosensitizer 201 The antibacterial activity was further improved as compared with a skin external preparation comprising a combination of No. 1 and undecylenic acid (salt or derivative) or Photosensitizer 201 and hinokitiol (salt or derivative).

The amount of the photosensitive element 201 is 0.0000
It is preferably from 1 to 0.1% by weight, more preferably 0.001% by weight.
0.01 to 0.01% by weight.

The amount of undecylenic acid, a salt thereof, or a derivative thereof is preferably 0.01 to 5% by weight, more preferably 0.1 to 1.0% by weight.

The compounding amount of hinokitiol, a salt thereof and a derivative thereof is preferably 0.00001 to 0.05% by weight.
More preferably, it is 0.00005 to 0.01% by weight.

[0015] The external preparation for skin in the present invention includes various components which are usually blended in pharmaceuticals, quasi-drugs, and skin cosmetics, for example, avocado oil, palm oil, peanut oil, rice bran oil, jojoba oil, orange roughy oil. , Macadamia nut oil, squalane, evening primrose oil, sesame oil, sunflower oil, safflower oil, carola oil, carnauba wax, paraffin wax, lanolin, diisostearyl malate, isostearyl alcohol, liquid paraffin, etc., glycerin, Moisturizing agents such as diglycerin, polyglycerin, sorbit, polyethylene glycol, 1,3-butylene glycol, collagen, hyaluronic acid,
Vitamin A oil, retinol, vitamin A such as retinol acetate, riboflavin, vitamin B ₂ such as riboflavin butyrate, vitamin B ₆ such as pyridoxine hydrochloride, L- ascorbic acid, magnesium L- ascorbyl phosphate, L- ascorbic acid Vitamin Cs such as sodium; pantothenic acids such as calcium pantothenate, D-pantoenyl alcohol, pantoenyl ethyl ether, and acetyl pantothenyl ethyl ether; vitamin Ds such as ergocalciferol and cholecalciferol; nicotinic acid and nicotinic acid Nicotinic acids such as amides and benzyl nicotinate;
Vitamin E such as α-tocopherol and tocopherol acetate, vitamin P such as vitamin P and biotin, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-
Methoxybenzophenone-5-sulfonic acid, 2-hydroxy-
Benzophenone derivatives such as sodium 4-methoxybenzophenone-5-sulfonate; paraaminobenzoic acid derivatives such as paraaminobenzoic acid, ethyl paraaminobenzoate and octyl paradimethylaminobenzoate; 2-ethylhexyl paramethoxycinnamate, mono-diparamethoxycinnamate Methoxycinnamic acid derivatives such as glyceryl 2-ethylhexanoate, salicylic acid derivatives such as octyl salicylate and myristyl salicylate, urocanic acid, 4-tert-butyl-4'-methoxydibenzoylmethane, 2- (2'-hydroxy-5 UV absorbers such as' -methylphenyl) benzotriazole, plant-based natural polysaccharides such as guar gum, locust bean gum, carrageenan, quince seed, pectin, mannan, microbial natural polysaccharides such as xanthan gum, dextran, curdlan, gelatin, Mosquito Animal-based polymers such as quinone, albumin, etc .; cellulose-based semi-synthetic polymers such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose and carboxymethylcellulose; starch-based semisynthetic polymers such as soluble starch, carboxymethyl starch and methyl starch; Alginate semi-synthetic polymers such as propylene glycol alginate and alginates; synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium polyacrylate, and polyethylene oxide; and inorganic high polymers such as bentonite, laponite, and colloidal alumina. Water-soluble polymers such as molecules, antioxidants such as dibutylhydroxytoluene, butylhydroxyanisole, and gallic acid esters, and higher fats Soaps, alkyl sulfates, polyoxyethylene alkyl ether sulfates, acyl methyl taurine salts, alkyl ether phosphate salts, anionic surfactants such as acyl amino acid salt, alkyl trimethyl ammonium chloride, dialkyl chloride dimethylammonium,
Cationic surfactants such as benzalkonium chloride, amphoteric surfactants such as alkyldimethylaminoacetate betaine, alkylamide dimethylaminoacetate betaine, and 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine; Surfactants such as ethylene nonionic surfactant and alcohol ester nonionic surfactant, sequestering agents such as sodium ethylenediaminetetraacetate, sodium polyphosphate, sodium metaphosphate, succinic acid, gluconic acid, placenta extract, and soybean Whitening agents such as extracts, glutathione, hydroquinone glycosides and other hydroquinones and derivatives thereof; anti-inflammatory agents such as glycyrrhizic acid, glycyrrhetinic acid, allantoin, azulene, hydrocortisone, and ε-aminocaproic acid; Astringents such as lanthanum, allantoin hydroxyaluminum, aluminum chloride, tannic acid, citric acid, and lactic acid; cooling agents such as menthol and camphor; antihistamines such as diphenhydramine hydrochloride, chlorpheniramine maleate; An inhibitor, a keratin exfoliating / dissolving agent such as salicylic acid, resorcin and the like can be added.

[0016]

EXAMPLES Further, the present invention will be described in more detail with reference to Examples.

The formulas of the examples of the present invention are shown below.

Example 1 Skin Gel (1) Purified Water 89.9985 (% by weight) (2) Carboxyvinyl Polymer 0.5 (3) Dipropylene Glycol 8.0 (4) Photosensitizer 201 0.001 (5) Glyceryl monoundecylenate 0.5 (6) Hinokitiol 0.0005 (7) Potassium hydroxide (10% by weight aqueous solution) 1.0 Manufacturing method: (2) and (3) were uniformly dissolved in (1). rear,
(4) to (6) are added, and then (7) is added to increase the viscosity.

Example 2 Oil-in-water emulsion ointment (1) White petrolatum 25.0 (% by weight) (2) Stearyl alcohol 25.0 (3) Glycerin 10.0 (4) Sodium lauryl sulfate 1.0 (5 ) Photosensitizer 201 0.005 (6) Undecylenic acid 0.1 (7) Hinokitiol 0.0001 (8) Purified water 38.8949 Production method: Mix and dissolve the oil phase components of (1) to (6) Make homogeneous and heat to 75 ° C. On the other hand, (7) is dissolved in (8) and heated to 75 ° C., and the oil phase component is added to this and emulsified.

Example 3 Antibacterial Lotion for Skin (1) Ethanol 10.0 (% by weight) (2) Hydroxyethylcellulose 1.0 (3) Glycerin 7.0 (4) Sodium Guaiazulene Sulfonate 0.5 (5) Photoelement 201 No. 0.001 (6) Potassium undecylenate 0.2 (7) Purified water 81.299 Production method: (1) to (6) are sequentially added to (7) and uniformly mixed and dissolved.

Example 4 Antibacterial lotion for skin (1) Ethanol 7.0 (% by weight) (2) 1,3-butylene glycol 6.0 (3) Condensed glycerin 2.0 (4) Polyoxyethylene cured castor Oil 0.6 (5) Photosensitizer 201 0.001 (6) Hinokitiol 0.001 (7) Fragrance 0.06 (8) Purified water 84.338 Manufacturing method: (1) to (7) in order (8) And uniformly mixed and dissolved.

Example 5 Antimicrobial Skin Emulsion (1) Squalane 5.0 (% by weight) (2) White Vaseline 2.0 (3) Beeswax 0.5 (4) Sorbitan Sesquioleate 0.8 (5) Polyoxyethylene (20E.O.) oleyl ether 1.2 (6) Undecylenic acid 0.5 (7) Propylene glycol 5.0 (8) Purified water 58.78989 (9) Carboxyvinyl polymer (1% by weight aqueous solution) 20.0 (10) Potassium hydroxide (10% by weight aqueous solution) 1.0 (11) Ethanol 5.0 (12) Fragrance 0.2 (13) Photosensitizer 201 0.001 (14) Acetyl hinokitiol 0.0001 Production method: The oil phase components (1) to (6) are mixed and heated to 75 ° C. to dissolve and homogenize. On the other hand, the aqueous phase components (7) to (9) are mixed and dissolved, heated to 75 ° C., the oil phase component is added, and the mixture is uniformly emulsified by a homomixer. To adjust. After cooling at 40 ° C (11)-
(14) is added and mixed.

Example 6 Antibacterial Skin Cream (1) Stearyl alcohol 6.0 (% by weight) (2) Stearic acid 2.0 (3) Undecylenic acid 1.0 (4) Hydrogenated lanolin 4.0 (5) ) Squalane 9.0 (6) Octyldodecanol 10.0 (7) Glyceryl monostearate 2.0 (8) Polyoxyethylene (25E.O.) Cetyl alcohol ether 3.0 (9) 1,3- Butylene glycol 6.0 (10) Purified water 56.895 (11) Fragrance 0.1 (12) Photosensitizer 201 0.005 Production method: First, the oil phases (1) to (7) are mixed and dissolved by heating. And maintain at 75 ° C. On the other hand, the aqueous phases (8) to (10) are mixed and dissolved by heating to 75 ° C., and the oil phase is added thereto with stirring to emulsify. After cooling at 40 ° C (11),
(12) is added and mixed.

Example 7 Hair Lotion (1) Purified water 41.394 (% by weight) (2) Polyoxyethylene (50E.O.) hydrogenated castor oil 2.0 (3) Ethanol 50.0 (4) Avocado oil 1.0 (5) Photosensitizer 201 0.005 (6) Hinokitiol 0.001 (7) Pyridoxine hydrochloride 0.5 (8) 1,3-butylene glycol 5.0 (9) Fragrance 0.1 Production method: ( After dissolving (2) in (1), components (3) to (9) are sequentially added and uniformly dissolved.

Example 8 Hair restorer (1) Purified water 30.395 (% by weight) (2) Polyoxyethylene (50E.O.) hydrogenated castor oil 3.0 (3) Ethanol 60.0 (4) Fragrance 1 (5) Tocopherol acetate 0.5 (6) Photosensitizer 201 0.005 (7) Glyceryl monoundecylenate 1.0 (8) Hop 50% by weight ethanol extract 3.0 (9) Propylene glycol 2.0 Production method: (2) is dissolved in (1), and components (3) to (9) are sequentially added and mixed to dissolve uniformly.

Further, those prepared in accordance with the formulations of the respective Examples but not containing undecylenic acid (salt, derivative) and / or hinokitiol (derivative) were prepared, and Comparative Examples 1 to 8 were obtained.

Next, with respect to the above Examples and Comparative Examples,
The antibacterial activity against Trichophyton, Acne, and Dandruff was evaluated. Per gram of sample, there are 10 ⁶ bacteria, Acne,
The fungus Trichophyton and dandruff are inoculated with 10 ⁵ cells at 37 ° C.
And at 25 ° C., respectively, and the viable cell count after 2 weeks was measured. In addition, the antibacterial activity was judged to be acceptable when the acne bacterium was killed 2 weeks later, and when the viable count of Trichophyton and dandruff was 1/1000 or less, it was judged as acceptable. The results of the antibacterial activity test were shown as "O" for those that passed, and "X" for those that failed. Table 1 shows the evaluation results.

[0028]

[Table 1]

As shown in Table 1, Examples 1 to 8
Showed sufficient antibacterial activity against all of the tested bacteria and fungi. However, in Comparative Examples 1 to 8 in which undecylenic acid (salt, derivative) and / or hinokitiol (derivative) were not blended, none of the bacterial strains passed.

Evaluation of skin irritation Skin irritation was evaluated in Examples 1 to 8 as samples.
Using a 1.0% by weight aqueous solution of each of the above, evaluation was performed by a 48-hour back obstruction sticking test by 30 male panelists, and the scores were scored according to the criterion shown in Table 2, and the average value of 30 individuals was obtained. Table 3 shows the results.

[0031]

[Table 2]

[0032]

[Table 3]

As shown in Table 3, as a result of the evaluation of skin irritation,
Almost no skin irritation was observed.

Evaluation of athlete's foot improvement Examples 1 to 3 and Comparative Examples 1 to 3
As a group, 20 males and females with athlete's foot and itching associated with athlete's foot were taken twice a day, in the morning and at night, in an appropriate amount, applied to the affected area, and subjected to a continuous use test for 2 months. The evaluation criteria are as specified below, and the results are shown in Table 4 with the number of persons who answered each evaluation.

"Athlete's foot improvement effect" Effective: Athlete's foot improved slightly Effective: Athlete's foot slightly improved Invalid: No change from before use "Itching inhibitory effect" Effective: Itching was improved Slightly effective: Itching was slightly improved Disabled: unchanged before use

[0036]

[Table 4]

As shown in Table 4, as a result of the evaluation of athlete's foot improvement,
90%, 85%, and 70% of panelists who answered "effective" in Examples 1 to 3 of the present invention, respectively. As a result of the itch improvement evaluation, "effective" in Examples 1 to 3 of the present invention. 85%, 85%, 75% of the panelists answered,
Control of athlete's foot and improvement of itching were observed, and very good results were obtained as compared with the comparative example.

Evaluation of Acne Improvement Examples 4 to 6 and Comparative Examples 4 to 6
Twenty young men and women with acne were taken as a group, taking an appropriate amount twice daily in the morning and evening, and having them applied to the entire face or the affected area. A continuous use test was conducted for two months.
The evaluation criteria are as specified below, and the results are shown in Table 5 by the number of persons who answered each evaluation.

"Acne improvement effect" Effective: Acne improved somewhat Effective: Acne somewhat improved Invalid: No change from before use

[0040]

[Table 5]

As shown in Table 5, 80% of the panelists who answered "effective" in Examples 4 to 6 of the present invention respectively.
%, 90%, and 75%, the effect of improving acne was high, and the difference from the comparative example was obvious.

Dandruff Inhibition Evaluation and Itching Inhibition Evaluation Using Examples 7 and 8 and Comparative Examples 7 and 8, daily 20 days before going to bed as a group of 20 adult men and women with dandruff and itching associated with dandruff An appropriate amount was taken by hand or directly applied to the scalp, and a continuous use test for dandruff suppression and itch suppression was carried out for two months. The evaluation criteria are as specified below, and the results are shown in Table 6 based on the number of persons who answered each evaluation.

"Darkness suppression effect" Effective: Slightly suppressed dandruff: Slightly suppressed dandruff Invalid: No change from before use "Itching suppression effect" Effective: Improved itching Slightly effective: Slightly improved itching Disabled: unchanged before use

[0044]

[Table 6]

As shown in Table 6, as a result of the dandruff suppression evaluation,
75% and 70% of panelists who answered "effective" in Examples 7 and 8 of the present invention respectively, and panelists who answered "effective" in Examples 7 and 8 of the present invention as a result of the itch suppression evaluation. Of 85% and 75%, respectively, showed suppression of dandruff and improvement of itch, and very good results were obtained as compared with the comparative example.

[0046]

As described in detail above, Photosensitizer No. 201 (Pionin), undecylenic acid, salts and derivatives thereof,
And a skin external preparation comprising one or more members selected from the group consisting of hinokitiol, salts and derivatives thereof, has low skin irritation and is excellent against Trichophyton, acne, dandruff, etc. Antibacterial action was obtained. In addition, these skin external preparations had an effect of suppressing itching due to athlete's foot and athlete's foot, an effect of improving acne, and an effect of suppressing itching due to dandruff and dandruff.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (reference) A61K 31/426 A61K 31/426 A61P 17/00 101 A61P 17/00 101 F term (reference) 4C083 AA082 AA112 AA122 AB032 AC012 AC022 AC072 AC102 AC112 AC122 AC182 AC251 AC252 AC352 AC432 AC442 AC792 AC861 AC862 AD092 AD282 AD512 AD551 AD552 AD662 CC17 CC24 CC37 DD23 DD27 DD31 DD33 DD41 EE10 EE14 EE23 EE50 4C086 AA01 AA02 BC82 MA03 MA28 NA06 A03 A02A03 A02A03 MA12 MA36 MA37 MA48 MA83 NA06 NA14 ZA90 ZB35

Claims (3)

[Claims] 1. Photosensitizer No. 201 (Pionin), undecylenic acid, salts and derivatives thereof, and hinokitiol,
An antibacterial skin external preparation comprising one or more selected from the group consisting of salts and derivatives thereof. 2. Photosensitizer No. 201 (Pionin), one or more selected from undecylenic acid, salts and derivatives thereof, and one or more selected from hinokitiol, salts and derivatives thereof An antibacterial skin external preparation consisting of 3. The antibacterial external preparation for skin according to claim 1, wherein the compounding amount of the photosensitizer No. 201 (pionin) is 0.0001% to 0.01%.