JP5929040B2 - External preparation composition and method for suppressing discoloration - Google Patents

Description

  The present invention relates to an external preparation composition containing salicylic acid.

  Salicylic acid has an exfoliating action and a comedone-decomposing action, and exerts acne treatment effects by promoting desquamation, so salicylic acid is blended in lotions and the like as an active ingredient of an acne remedy. However, since salicylic acid is polymerized by light and temperature to form a yellow substance, a preparation containing salicylic acid has a problem that the preparation turns yellow when exposed to light over time. In order to prevent this, measures such as filling a container that does not transmit light have been taken, and the degree of freedom of the container has been limited.

JP-A-4-217925 JP-T 9-510976

  This invention is made | formed in view of the said situation, and it aims at providing the external preparation composition containing a salicylic acid which suppressed discoloration of the salicylic acid by light exposure, and the discoloration was suppressed.

  As a result of intensive studies to achieve the above object, the present inventors have determined that (A) salicylic acid, (B) ethanol and / or propanol, and (C) polyoxyethylene alkyl ether having HLB of 15 or more in specific amounts. In addition, the content ratio of the (A) component and the (B) component represented by (B) / (A) is set to 5 or more, thereby suppressing discoloration of salicylic acid due to light exposure and containing salicylic acid. It has been found that the discoloration of the preparation to be suppressed can be suppressed, and has led to the present invention.

Accordingly, the present invention provides the following external preparation composition and method for suppressing discoloration.
[1]. (A) Salicylic acid 0.1 to 0. 5% by mass, (B) 10 to 25% by mass of ethanol and / or propanol, (C) 1.5 to 5% by mass of polyoxyethylene alkyl ether whose HLB is 15 or more, and (D) water. External preparation composition whose content mass ratio of (A) component represented by B) / (A) and (B) component is 40-250.
[2]. The external preparation composition according to [1], which is filled in a transparent container.
[3]. Furthermore, (E) The external preparation composition of [1] or [2] containing a polyhydric alcohol.
[4]. (E) External preparation composition as described in [3] whose content of a component is 10-50 mass% with respect to the whole external preparation composition.
[5]. The external preparation composition according to any one of [1] to [4], wherein the component (C) is polyoxyethylene (15) cetyl ether.
[6]. The external preparation composition according to any one of [1] to [5], which is a liquid agent.
[7]. (A) Salicylic acid 0.1 to 0. In an external preparation composition containing 5% by mass and (D) water, (B) 10 to 25% by mass of ethanol and / or propanol, and (C) a polyoxyethylene alkyl ether having an HLB of 15 or more 1.5 to The above (5), which is blended so that the mass ratio of the component (A) and the component (B) represented by (B) / (A) is 40 to 250, while blending 5% by mass. A) A method for suppressing discoloration of an external preparation composition containing salicylic acid due to light exposure.
[8]. (A) Salicylic acid 0.1 to 0. In 5% by weight, and (D) external preparation composition containing water, (B) ethanol and / or propanol 10-25% by weight, a polyoxyethylene alkyl ether is (C) HLB is 15 or more 1.5 to 5 In addition to blending 10% by mass and 10% by mass of (E) polyhydric alcohol, the mass ratio of component (A) and component (B) represented by (B) / (A) is 40 to 250. A method for suppressing discoloration due to light exposure of the external preparation composition containing (A) salicylic acid, which is blended as described above.

  ADVANTAGE OF THE INVENTION According to this invention, the external preparation composition containing a salicylic acid which suppressed discoloration of the salicylic acid by light exposure and the discoloration was suppressed can be provided.

Hereinafter, the present invention will be described in detail.
The external preparation composition of the present invention comprises (A) 0.1-5% by mass of salicylic acid, (B) 3-25% by mass of ethanol and / or propanol, and (C) polyoxyethylene alkyl ether 0 having an HLB of 15 or more. The content ratio of the component (A) and the component (B) represented by (B) / (A) is 5 or more.

(A) Salicylic acid Salicylic acid has a bactericidal action, an anti-inflammatory action, etc. in addition to the stratum corneum peeling / dissolving action, and in a double-blind clinical trial, a therapeutic effect against acne vulgaris has been confirmed, Widely used as an active ingredient in acne treatments.

(B) Ethanol and / or propanol Ethanol and propanol function as a discoloration inhibitor for salicylic acid. Ethanol and propanol can be used regardless of whether they are modified or unmodified. Specifically, absolute ethanol manufactured by Gansu Chemical Industry Co., Ltd., general alcohol 95-degree synthetic unmodified product manufactured by Mitsubishi Chemical Co., Ltd., government-specified ethanol manufactured by Shinwa Alcohol Co., Ltd., Katayama Chemical Industry Co., Ltd. Examples include propanol manufactured by BASF Japan Ltd.

  In order to obtain the discoloration suppressing effect of the present invention, the contents of (A) salicylic acid, (B) ethanol and / or propanol, (B) / (A) represented by (A) component and (B) component The content mass ratio is important.

  From the viewpoint of the effect of suppressing discoloration, the content of the component (A) is 0.1 to 5% by mass, preferably 0.2 to 3% by mass, and more preferably 0 to the whole external preparation composition. 0.5 to 2% by mass. (B) Content of a component is 3-25 mass% with respect to the whole external preparation composition, Preferably it is 10-25 mass%, More preferably, it is 20-25 mass%. In addition, (B) component can be used individually by 1 type or in combination of 2 or more types, and when using 2 or more types, it is a total amount of 2 types. If the content of the component (B) is too large, irritation to the skin increases and the usability deteriorates, so it is desirable to select an upper limit of 25% by mass or less.

  The mass ratio of the component (A) and the component (B) represented by (B) / (A) is 5 or more, preferably 10 or more, and more preferably 40 or more. By setting it to 5 or more, the intended discoloration suppressing effect can be obtained. On the other hand, when the ratio is less than 5, the solubility of (A) salicylic acid is lowered, causing a problem of crystal precipitation. The upper limit is not particularly limited, but 250 can be selected.

(C) Polyoxyethylene alkyl ether with HLB of 15 or more Polyoxyethylene alkyl ether functions as a discoloration inhibitor for salicylic acid. The polyoxyethylene alkyl ether needs to have an HLB value of 15 or more, and is preferably a polyoxyethylene alkyl ether having 17 to 20. If the polyoxyethylene alkyl ether has an HLB value that is too low, (A) salicylic acid cannot be sufficiently solubilized. As for carbon number of the alkyl group of polyoxyethylene alkyl ether, 12-22 are preferable. Although the upper limit of HLB is not specifically limited, 20 can be selected.

  Specific examples of the polyoxyethylene alkyl ether having an HLB of 15 or more include, for example, polyoxyethylene (15) cetyl ether (HLB = 15.5), polyoxyethylene (20) behenyl ether (HLB = 16.5), polyoxyethylene (23) cetyl ether (HLB = 18), polyoxyethylene (25) cetyl ether (HLB = 18.5), polyoxyethylene (30) cetyl ether (HLB = 19.5) , Polyoxyethylene (20) oleyl ether (HLB = 17), polyoxyethylene (30) behenyl ether (HLB = 18), polyoxyethylene (20) stearyl ether (HLB = 18), polyoxyethylene (21) lauryl Ether (HLB = 19), polyoxyethylene (25) And the like can be mentioned selling ether (HLB = 19.5). Among them, polyoxyethylene (15) cetyl ether (HLB = 15.5), polyoxyethylene (20) behenyl ether (HLB = 16.5), polyoxyethylene (20) oleyl ether (HLB = 17), polyoxy Ethylene (30) behenyl ether (HLB = 18), polyoxyethylene (23) cetyl ether (HLB = 18), polyoxyethylene (25) cetyl ether (HLB = 18.5), polyoxyethylene (30) cetyl ether (HLB = 19.5), polyoxyethylene (20) stearyl ether (HLB = 18), polyoxyethylene (21) lauryl ether (HLB = 19), polyoxyethylene (25) lauryl ether (HLB = 19.5) ) Etc. are more effective. These polyoxyethylene alkyl ethers can be used singly or in appropriate combination of two or more. Even if it is a polyoxyethylene alkyl ether having an HLB value of less than 15 alone, it is used by adjusting the HLB value of the surfactant as a whole to 15 or more in combination with the surfactants exemplified above. can do.

  “HLB” means a hydrophilic-lipophilic balance, that is, a relative strength between hydrophilicity and lipophilicity of a molecule of a surfactant. This is a quantitative representation of the oil balance. Specifically, it is a value determined by the Griffin method (see Yoshida, Shindo, Ogaki, Yamanaka, edited by “New Edition Surfactant Handbook”, Engineering Books Co., Ltd., 1991, page 234).

  (C) Content of a component is 0.1-5 mass% with respect to the whole external preparation composition, 0.5-5 mass% is preferable, and 1.5-5 mass% is more preferable. In addition, when content of (C) component exceeds 5 mass%, a bubble will generate | occur | produce at the time of manufacture and manufacturability will worsen, Therefore An upper limit shall be 5 mass% or less.

(D) Water Water is not particularly limited, and purified water, distilled water, ion exchange water, clean water, and the like can be used as appropriate. In this case, water is blended as a balance and adjusted by the amount of other components, but is preferably 10 to 97% by mass, for example.

  It is preferable to mix | blend (E) polyhydric alcohol with the external preparation composition of this invention from the point of the discoloration suppression of a salicylic acid and the low temperature stability improvement of an external preparation composition. The polyhydric alcohol is an alcohol having two or more hydroxyl groups in one molecule, and specifically includes glycerin, 1,3-butylene glycol, ethylene glycol, polypropylene glycol, polyethylene glycol (Macrogol 400) and the like. These can be used individually by 1 type or in combination of 2 or more types. 10-50 mass% is preferable with respect to the whole external preparation composition, and, as for content of a polyhydric alcohol, 20-30 mass% is more preferable. If the content is less than 10% by mass, there is a risk of crystal precipitation at a low temperature, and if it exceeds 50% by mass, stickiness may occur and the usability may deteriorate.

  The external preparation composition of this invention can mix | blend arbitrary components in the range which does not impair the effect of this invention other than said (A)-(E) component. Examples of the optional component include a polymer compound, a pH adjuster, a chelating agent, an antiseptic, a fragrance, a dye, and the like, which can be used alone or in appropriate combination of two or more.

  The polymer compound is preferably a polymer compound that is soluble in water or a mixed solvent system of lower alcohol / water, such as cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, carmellose, croscarmellose, methylcellulose, Processed starch such as partially pregelatinized starch, polyvinyl alcohol, polyvinylpyrrolidone, crospovidone, polyethylene glycol, xanthan gum, carrageenan, sodium alginate, gum arabic, guar gum, locust bean gum, pullulan, gelatin, carboxyvinyl polymer, acrylic acid / methacrylic acid Examples thereof include alkyl copolymers and sodium polyacrylate. Although content of a high molecular compound is suitably selected by the setting viscosity of the external preparation composition for acne, 0.01-10 mass% is preferable with respect to the whole external preparation composition, More preferably, it is 0.05-5. % By mass.

  pH adjusters include inorganic acids such as hydrochloric acid, phosphoric acid and boric acid, organic acids such as lactic acid, tartaric acid and citric acid, sodium hydroxide, potassium hydroxide, monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine And various amines such as triisopropanolamine and tromethamine, phosphates such as potassium hydrogenphosphate and sodium hydrogenphosphate, and organic salts such as sodium citrate and sodium lactate. Diisopropanolamine, triisopropanolamine, and triethanolamine are preferred because pH stability is particularly good when an acidic drug is used. The content of the pH adjusting agent can be appropriately selected depending on the set pH.

  Examples of the chelating agent include pyrophosphate, hexametaphosphate, gluconate, edetate and the like. When mix | blending a chelating agent, 0.001-5 mass% is preferable with respect to the whole external preparation composition, More preferably, content of a chelating agent is 0.01-5 mass%.

  Examples of the preservative include dibutylhydroxytoluene, benzoic acids, parabens, benzalkonium chloride, benzethonium chloride, sorbic acid and its salts, boric acid, borax and the like. Dibutylhydroxytoluene, citric acid and its salts are preferred. When mix | blending antiseptic | preservative, 0.005-5 mass% is preferable with respect to the whole external preparation composition, More preferably, content of antiseptic | preservative is 0.01-1 mass%.

  As the pigment, any pigment that can be used for external preparations (cosmetics, pharmaceuticals) such as acid dyes, basic dyes, oxidation dyes, and pigments can be arbitrarily used. As the fragrance, a natural fragrance or a synthetic fragrance can be used without any particular limitation. Examples of natural flavors include vegetable flavors such as peppermint oil, spearmint oil, jasmine oil, lemon oil, orange oil, lime oil, mandarin oil, rose oil, rosemary oil and the like. Synthetic fragrances include monoterpenes, diterpenes, sesquiterpenes, etc., specifically geraniol, linalool, citronellol, nerol, limonene, pinene, camphene, citral, citronellal, cineole, curcumene, hinokic acid, hinokiol, phytol, etc. Is mentioned. When mix | blending a pigment | dye and a fragrance | flavor, 0.0001-5 mass% is preferable with respect to the whole external preparation composition, and, as for each content of a pigment | dye and a fragrance | flavor, More preferably, it is 0.0001-1 mass%.

  Although it does not specifically limit as a dosage form of the external preparation composition of this invention, A liquid agent is preferable. As for the viscosity of the external preparation composition of this invention, 0.5-50,000 mPa * s is preferable, More preferably, it is 0.5-1,000 mPa * s, More preferably, it is 0.5-500 mPa * s. . If the viscosity is too low, the usability such as dripping of the liquid may be deteriorated, and if it is too high, the liquid may not be easily discharged from the bottle or may not be easily extended to the affected area. In addition, in this invention, a viscosity is a value in 25 degreeC measured according to the Japanese Pharmacopoeia general test method viscosity measuring method and the 2nd method rotational viscometer method.

  The pH of the external preparation composition of the present invention is more preferably 2 to 5 and more preferably 3 to 4 from the viewpoints of stratum corneum peeling, dissolution action and skin irritation. If it is in the acidic range from pH 2, skin irritation may occur, and the effect of salicylic acid is more exerted by setting this range. In addition, in this invention, pH is the value measured by the Japanese Pharmacopoeia general test method and the pH measurement method.

  Since the external preparation composition of the present invention contains salicylic acid, it is suitable for acne treatment / prevention, keratin care agent, tinea remedy, and bactericidal agent.

  Since the external preparation composition of the present invention has the effect of suppressing discoloration of the composition resulting from salicylic acid, the container is not particularly limited and can be filled into any container including a transparent container. In the present invention, the transparent container is defined as follows. A transparent container means that when implemented under an illuminance of about 300 lux, a “○” mark with an outer diameter of 7.0 mm and an inner diameter of 5.5 mm drawn on a gray scale of 256 gradations with a density of 220 gradations is passed through the container. It shall have transparency which can be visually recognized.

  Glass, resin, or the like can be used as the material of the container. Specific examples of the resin include polyethylene, polypropylene, polyethylene terephthalate, polyethylene naphthalate, polyarylate, polystyrene, acrylonitrile butadiene styrene, polyester, polyphenylene ether, polycarbonate, polysulfone, polyamide, hard vinyl chloride, polyimide, cellulose acetate, and co-polymers thereof. A polymer, a mixture, etc. are mentioned. In addition to those containing or coated with ultraviolet absorbers and pigments, it is possible to fill transparent containers. This invention can also be set as the external preparation composition with which a transparent container is filled, and can also be set as the external preparation product which consists of an external preparation composition and the transparent container filled with this.

  Although the manufacturing method of the external preparation composition of this invention is not specifically limited, For example, (A) salicylic acid is melt | dissolved in (B) ethanol and / or propanol and (C) polyoxyethylene alkyl ether whose HLB is 15 or more. (D) The method of adding to water is mentioned. In (D), other components may be blended, and for example, an aqueous solution in which the polyhydric alcohol is dissolved may be used. The order in which the component (A) is dissolved in the component (B) and the component (C) is not particularly limited. The solution (A) is dissolved in the component (B) and heated to melt (C). Ingredients may be added. In addition, it is desirable to filter the obtained liquid with a filter having a pore diameter of 0.45 to 100 μm.

  Moreover, this invention is (A) 0.1-5 mass% of salicylic acid, and (D) the external preparation composition containing water, (B) ethanol and / or 3-25 mass% of propanol, (C) HLB contains. While blending 0.1-5 mass% of polyoxyethylene alkyl ether which is 15 or more, the content mass ratio of (A) component and (B) component represented by (B) / (A) is 5 or more. The above-described (A) salicylic acid-containing external preparation composition containing the above-described (A) is provided with a method for suppressing discoloration. Preferred components, amounts, etc. are the same as above.

EXAMPLES Hereinafter, although an Example , a reference example, and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, unless otherwise specified, “%” in the composition indicates mass%, the ratio indicates the mass ratio, and the amount of each component in the table is an amount converted into a pure component.

[Examples 1-5, Reference Examples 1-18 , Comparative Examples 1-7]
External preparation compositions (lotion agents) having the compositions shown in Tables 1 to 5 were prepared by the following method. The following evaluation was performed about the obtained external preparation composition. The results are also shown in the table.
<Preparation method>
(A) Salicylic acid was dissolved in (B) ethanol and / or propanol, heated and melted (C) polyoxyethylene alkyl ether was added and dissolved, and this liquid was mixed with polyhydric alcohol (D) The mixture was added to purified water and stirred sufficiently to obtain an external preparation composition (lotion agent).

<Measurement of formulation color tone>
The external preparation composition (lotion agent) was filled in a colorless and transparent glass container and allowed to stand in a place exposed to direct sunlight (irradiation amount: 3.5 MJ / m ² ). Then, b * value of the external preparation composition (lotion agent) before and after irradiation was measured with a color difference meter (Nippon Denshoku Industries Co., Ltd. SE200), and the following Δb * value was obtained.
Δb * value = external preparation composition after irradiation with sunlight b * value−b * value before irradiation with sunlight From the result of the obtained Δb * value, suppression of color tone change is shown by the following criteria. The range of 〜 to △ is the allowable range.
[Criteria]
◎: Δb * value is less than 0.35 ○: Δb * value is 0.35 or more and less than 0.6 Δ: Δb * value is 0.6 or more and less than 1.0 x: Δb * value is 1.0 or more

Claims (8)

(A) Salicylic acid 0.1 to 0. 5% by mass, (B) 10 to 25% by mass of ethanol and / or propanol, (C) 1.5 to 5% by mass of polyoxyethylene alkyl ether whose HLB is 15 or more, and (D) water. External preparation composition whose content mass ratio of (A) component represented by B) / (A) and (B) component is 40-250.   The external preparation composition according to claim 1, wherein the composition is filled in a transparent container.   Furthermore, the external preparation composition of Claim 1 or 2 containing (E) polyhydric alcohol.   The external preparation composition according to claim 3, wherein the content of the component (E) is 10 to 50 mass% with respect to the entire external preparation composition.   (C) A component is polyoxyethylene (15) cetyl ether, The external preparation composition of any one of Claims 1-4.   It is a liquid agent, The external preparation composition of any one of Claims 1-5. (A) Salicylic acid 0.1 to 0. In an external preparation composition containing 5% by mass and (D) water, (B) 10 to 25% by mass of ethanol and / or propanol, and (C) a polyoxyethylene alkyl ether having an HLB of 15 or more 1.5 to The above (5), which is blended so that the mass ratio of the component (A) and the component (B) represented by (B) / (A) is 40 to 250, while blending 5% by mass. A) A method for suppressing discoloration of an external preparation composition containing salicylic acid due to light exposure. (A) Salicylic acid 0.1 to 0. In 5% by weight, and (D) external preparation composition containing water, (B) ethanol and / or propanol 10-25% by weight, a polyoxyethylene alkyl ether is (C) HLB is 15 or more 1.5 to 5 In addition to blending 10% by mass and 10% by mass of (E) polyhydric alcohol, the mass ratio of component (A) and component (B) represented by (B) / (A) is 40 to 250. A method for suppressing discoloration due to light exposure of the external preparation composition containing (A) salicylic acid, which is blended as described above.