JP3461020B2 - External preparation for skin - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to kojic acid and / or kojic acid.
Eliminates the immediate coloring of derivatives of
Over time without color, reduced dispersibility and caking phenomenon
It is a skin external preparation that is highly stable and has excellent usability.
More specifically, the above-mentioned kojic acid and / or a derivative thereof
And an ultraviolet light scattering agent coated with a first coating agent comprising a specific compound, and a surfactant as a second coating agent.
As an active ingredient, one with coals attached as an auxiliary
The present invention relates to an external preparation for skin contained . [0002] Kojic acid or a kojic acid derivative (hereinafter referred to as "kojic acid" )
These are sometimes collectively referred to simply as "kojic acids".
You. ) Is the active ingredient of various external preparations including cosmetics
Have been studied by the present inventors for many years.
As a result of repeated studies, for example,
No. 569, Japanese Patent Publication No. 58-21151, Japanese Patent Publication No.
No. 58-22152, Japanese Patent Publication No. 60-7961
Bulletin, JP-B-60-9722, JP-B-60-100
No. 05, Japanese Patent Publication No. 61-1047, Japanese Patent Publication No. 6
No. 1-60801, Japanese Patent Publication No. 62-3820,
It is disclosed in JP-B-63-24968 and the like.
Kojic acids are also specified in the patent gazette.
Inhibits the action of tyrosinase present in human skin
And has a remarkable melanin inhibitory effect,
Used as an active ingredient in various skin external preparations, including cosmetics
Has been used for many external applications
It is expected to be used as a component of the agent. However, kojic acids are delicate substances that are difficult to control in the formulation, become unstable when kept in a solution state at a high temperature or stored for a long period of time, and after the formulation, during the distribution process in storage or sale and during use. It has the disadvantage that it is colored over time even during storage after use. Therefore, in the past, various formulations have been devised so as not to impair the product value at the distribution stage at the time of formulation. Disclosure of such technology includes:
For example, Japanese Patent Application Laid-Open Nos.
JP-A-108804, JP-A-63-188609, JP-A-63-270609, JP-A-64-8
No. 3008 and JP-A-3-101609. JP-A-61-109705 discloses a method in which kojic acid is clathrated with cyclodextrin to increase the stability of kojic acid itself.
No. 26,061 discloses the addition of kojic acid purified by sublimation. However, there is a problem that cyclodextrin cannot be added in a larger amount due to the feeling of use of the preparation. Further, only a small amount of kojic acid obtained by sublimation is collected, and there is little possibility that it will be used for actual formulation, and it is not always a preferable method. Further, JP-A-62-108804, JP-A-64-83008 and JP-A-63-18860.
No. 9 discloses a method of blending various ultraviolet absorbers, but the coloration of kojic acids is caused not only by ultraviolet irradiation but also by heating or the like. However, these methods are also difficult to say as complete coloring prevention methods, and it has been difficult to select a substance suitable for formulation from the viewpoint of feeling of use and skin irritation. Attempts have been made to solve the above-mentioned drawbacks by using an ultraviolet light scattering agent. However, this ultraviolet light scattering agent immediately reacts with kojic acids to be colored yellow or to be formulated. May cause the ultraviolet scattering agent to develop color over time, and the dispersibility may decrease, especially in liquid preparations such as emulsions adjusted to the optimal pH range (4 to 5) to ensure the stability of kojic acids as much as possible. This causes a problem that the original effect of the ultraviolet scattering agent is not exhibited due to caking or the like. SUMMARY OF THE INVENTION The present invention relates to kojic acids
And an ultraviolet light scattering agent coated with a first coating agent comprising a specific compound, and a surfactant as a second coating agent.
By using a mixture of coals as an auxiliary , the above-mentioned problem, that is, not only the problem of immediate coloring of kojic acids is eliminated, but also the coloring of the ultraviolet scattering agent, reduced dispersibility and caking phenomenon. It is an object of the present invention to provide a skin external preparation having a good feeling of use that does not occur. The inventor of the present invention has conducted intensive studies to solve the above-mentioned problems, and as a result, if an ultraviolet scattering agent surface-treated with a specific coating agent is used together, A phenomenon in which immediate coloring and decomposition of kojic acids are suppressed has been found. Then, when this was formulated into a pH range of 4 to 5 and the stability was observed, there was no coloring of the ultraviolet scattering agent,
The inventors have found that the dispersibility is good and that the caking phenomenon does not occur, and the present invention has been completed. That is, according to the present invention, kojic acid and / or its derivative and sodium stearate
Thorium, aluminum stearate, isostearin
Acid, magnesium myristate, isopromyristate
A UV-scattering agent coated with a first coating selected from the group consisting of pills, zinc palmitate and oleyl oleate , a surfactant as a second coating,
Characterized in that it contains, as an active ingredient, a substance which has been adhered as an auxiliary agent, the immediate coloring of kojic acid and / or a kojic acid derivative is eliminated, and the coloring of an ultraviolet scattering agent,
A skin external preparation that is stable over time and has a good feeling of use without lowering dispersibility and causing a caking phenomenon is provided. The kojic acid used in the present invention (5-
(Oxy-2-hydroxymethyl-γ-pyrone) is a pure product of 5-oxy-2-hydroxymethyl-γ-pyrone, and kojic acid obtained by culturing a known strain having a kojic acid-producing ability as a main component. A fermentation solution, a concentrated solution of the fermentation solution, and a product obtained by extracting and crystallizing kojic acid from the fermentation solution are used. Examples of the kojic acid derivative include those disclosed in JP-B-60-10005, JP-B1-45472, JP-B3-74229, JP-B-58-22151, and JP-B-58-22151. Kosho 58-2
By the 2-position of -CH ₂ OH group of the ester compound and kojic acid kojic acid disclosed in 2152 JP binding the sugar, solely or kojic acid molecule kojic acid derivatives of known stabilized Alternatively, two or more kinds can be used in combination. In the present invention, examples of the ultraviolet scattering agent used include the following. That is, aluminum powder, mica titanium, yellow iron oxide, bismuth oxychloride,
Kaolin, black titanium oxide, black iron oxide, gunjo, gunjo violet, gunjo pink, aluminum silicate, aluminum magnesium silicate, calcium silicate, magnesium silicate, light calcium carbonate, light magnesium carbonate, diatomaceous earth, konjo, Zinc flower, alumina, aluminum oxide / cobalt, chromium oxide, zirconium oxide, titanium oxide, magnesium oxide, heavy calcium carbonate, heavy magnesium carbonate, aluminum hydroxide, chromium hydroxide, zeolite, sericite, talc, titanium yellow, titanium Cobalt acid, Pearl powder, Bengala, Bentonite, Mica, Manganese violet, Silicic anhydride, Aluminum silicate anhydrous,
Montmorillonite, barium sulfate, 5-chlorouracil, guanine, cytosine and the like are used, and preferably, red iron oxide, titanium oxide, chromium oxide, black iron oxide, zirconium oxide, yellow iron oxide, zinc white, alumina, magnesium oxide , Barium sulfate, mica, talc, sericite, konjo, kaolin, aluminum hydroxide, gunjo, montmorillonite, calcium carbonate, silicic anhydride, zeolite, diatomaceous earth, 5-chlorouracil, guanine, cytosine. The first coating agent used for applying the surface treatment to these ultraviolet light scattering agents includes sodium stearate.
, Aluminum stearate, isostearic acid,
Magnesium myristate, isopropyl myristate
, Zinc palmitate and oleyl oleate
A compound selected from the group consisting of: An ultraviolet scattering agent coated with these first coating agents , and a surfactant as a second coating agent,
Higher alcohols, polyhydric alcohols, sugar alcohols, etc.
By using alcohol as an auxiliary ,
The effects of the present invention can be further enhanced. [0014] The second coating is mainly is effective to improve the dispersibility in water with stabilizing the surface layer has been treated by the first coating, alcohol surfactant is a second coating Is useful as an auxiliary agent for increasing the adhesion and affinity to the first coating agent, and it is considered that these interactions enhance the effect. As the surfactant used as the second coating agent, any of a natural product and a chemically synthesized product can be used, and is appropriately selected from amphoteric, anionic, nonionic, and cationic surfactants in consideration of safety. can do. Any combination of these surfactants can be used, but it is preferable to use a surfactant whose HLB value is adjusted in the range of 6 to 12. Among the alcohols used as auxiliaries, higher alcohols include, for example, aralkyl alcohol, isostearyl alcohol, octyldodecanol, olive oil alcohol, oleyl alcohol, stearyl alcohol, cetanol, cetostearyl alcohol, decyltetradecanol, Hydroaviethyl alcohol, castor oil alcohol, hexyl decanol, heptyl undecanol, behenyl alcohol, jojoba alcohol, myristyl alcohol, lauryl alcohol, etc. are mentioned, but in view of workability, a fluid form is preferable to a solid form. . Further, as the polyhydric alcohol, for example,
Alkylene (15-18) glycol, alkylene (20-30) glycol, ethylene glycol,
Glycerin, highly polymerized polyethylene glycol, diglycerin, dipropylene glycol, tetramethyltrihydroxyhexadecane, triethylene glycol, 1,3
-Butylene glycol, propylene glycol, hexylene glycol, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 4
00, polyethylene glycol 600, polyethylene glycol 1000, polyethylene glycol 1500,
Examples include polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 20,000, polypropylene glycol 400, and polypropylene glycol 1200. Examples of the sugar alcohol include fructose, xylitol, D-xylose, sorbitol, D-sorbitol, glucose, maltitol, maltose, D-mannitol and the like. The ultraviolet scattering agent surface-treated with these coating agents (hereinafter sometimes simply referred to as "ultraviolet scattering agent") can be obtained, for example, as follows, but is not limited thereto. Not something. First, an untreated ultraviolet scattering agent is used in an amount of usually 0.01 to 0.2 μm, preferably 0.03 μm.
To a particle size of 0.07 [mu] m, to which the first coating component is added, and the surface is treated by a known method. Then the second
By adding and kneading a surfactant, which is a coating agent, with an alcohol as an auxiliary agent , the first coating agent and
And an ultraviolet scattering agent coated with the second coating agent is obtained.
You . This is stirred and dispersed while being added little by little to water, and a previously prepared aqueous solution of kojic acids is added to form a desired dosage form. As another method, for example, a surfactant is dissolved or dispersed in a lipophilic solvent (for example, hexane or the like), and an ultraviolet scattering agent previously surface-treated with the first coating agent is added thereto . Surfactants which are two coating agents
Is mixed with an auxiliary agent composed of alcohols . In this case, any of a wet method and a dry method may be used, but a desired powder can be obtained by drying after a filtration step. When this powder is blended with a desired kojic acid preparation, an excellent preparation aimed at by the present invention can be obtained. As described above, the ultraviolet scattering agent used in the present invention needs to be separately prepared before adding kojic acids, and if this procedure is not mistaken, a known technique can be arbitrarily combined and formulated. is there. In the present invention, the amounts of the kojic acids and the ultraviolet light scattering agent are as follows: creams, lotions, emulsions, packs, lotions, essences, and other cosmetics;
In any case where the composition is used as an external preparation such as a poultice or a plaster, the ultraviolet light scattering agent is contained in the preparation in an amount of 0.0001 to 20% by weight, preferably 0.01 to 20% by weight.
To 10% by weight, and kojic acid is 0.001 to 10% by weight.
% By weight, preferably in the range of 0.1 to 5% by weight. The external preparation for skin of the present invention is not particularly limited as long as it is suitable for external application, and as described above, for example, cataplasms, plasters, pastes, creams, ointments, aerosols, emulsions, lotions, It is widely used in known forms acceptable as various dosage forms of pharmaceuticals such as emulsions, essences, packs, gels, powders, foundations, sun care, bath salts, etc., quasi-drugs, and cosmetics. When preparing the external preparation of the present invention, various known active ingredients usually used, for example, carpronium chloride, cepharanthin, vitamin E, vitamin E nicotinate, nicotinic acid, nicotinamide, benzyl nicotinate, and show Peripheral vasodilators such as tincture tincture and pepper tincture, cooling agents such as camphor and menthol,
Animals such as antibacterial agents such as hinokitiol, benzalkonium chloride, undecylenic acid, anti-inflammatory agents such as lysozyme chloride, glycyrrhizin, allantoin, fairing agents such as ascorbic acid and arbutin, placenta extracts, liver extracts, and lactic acid bacteria culture extracts Various extracts derived from plants and microorganisms can be appropriately added and used according to the purpose at that time. In addition, the aforementioned pharmaceuticals, quasi-drugs, and cosmetics, as well as known active ingredients and base components such as oils and fats, if necessary, known humectants, preservatives, antioxidants, ultraviolet absorbers,
Various additives such as a chelating agent, a pH adjuster, a fragrance, and a coloring agent can be used in combination. The following are examples and test examples of the effects thereof, which do not limit the present invention in any way. <Test Example 1> Coloring prevention effect test Test Method A formulation was prepared by mixing the following emulsion base with kojic acid, a kojic acid derivative or an ultraviolet scattering agent shown in Tables 1 and 2. These were dispensed into 2 oz. Bottles, shielded from light with aluminum foil, and stored in a thermostat at 45 ° C. for one month. One month later, ΔE (color difference) was measured using a color difference meter Z-1001DP of Nippon Denshoku Co., Ltd. At the same time, a feeling of use (comparison with the start of the test) was also evaluated using the preparation one month later.
Note that ΔE was calculated by the following equation (1). ΔL = Lt−L0 Δa = at−a0 Δb = bt−b0 where L0, a0, b0: La before storage at 45 ° C.
b value Lt, at, bt: Lab value after one month at 45 ° C. ΔE = (ΔL) 2+ (Δa) 2+ (Δb) 2 (1) Emulsion base (% by weight) used in test (A) Polyoxyethylene behenyl ether (20E.0.) 0.50 Polyoxyethylene sorbite (60E.0.) Tetraoleate 1.00 Lipophilic glyceryl monostearate 1.00 Stearic acid 0.50 Behenyl alcohol 0 .50 Natural vitamin E 0.02 Preservatives Appropriate amount (B) 1,3-butylene glycol 5.00 Carboxyvinyl polymer 0.10 N-lauroyl-L-sodium glutamate 0.50 Heating and dissolving components belonging to production method (A) (Oil phase), separately (B)
Was dissolved by heating (aqueous phase). The aqueous phase was added to the oil phase, stirred and emulsified, and then cooled to obtain an emulsion base. 2. Test Results The results for the present invention are as shown in Table 1, and the results for the comparative examples are as shown in Table 2. [0026] [0027] As is apparent from the above results, the present invention significantly reduces the coloring of kojic acid or its derivative (glucose) over time without impairing the preparation characteristics of kojic acid or its derivative (glucose) as compared with the control. Suppressed (these can clearly recognize the coloring suppression effect not only by the value of ΔE but also visually). Further, it was confirmed that the preparation did not develop color of the ultraviolet light scattering agent and had a good feeling in use without lowering dispersibility or causing a caking phenomenon. Formulation Examples The formulation examples of the present invention are shown below. In addition, in the formulation examples, "appropriate amount" means an amount that makes the entire formulation 100% by weight. <Prescription example 1> Cream (% by weight) A Monostearic acid Polyethylene glycol (40E.0.) 2.0 Self-emulsifying glyceryl monostearate 5.0 Stearic acid 5.0 Behenyl alcohol 1.0 Liquid paraffin 6 3.0 Olive oil 3.0 Carrot oil 3.0 Glyceryl trioctanoate 10.0 Polyoxy isostearate Ethylene hydrogenated castor oil (60E.0.) 1.0 Ultraviolet scattering agent (used in Example 3) 0.7 B Koji Acid 5.0 Glycerin 5.0 Ethyl paraben 0.1 Polyvinyl alcohol (PVA) 0.1 Purified water Amount The components belonging to A are heated and dissolved. Separately, the components belonging to B are dissolved by heating. B was added to A, stirred, emulsified, and cooled to produce a cream. <Formulation Example 2> Emulsion (% by weight) A Polyoxyethylene sorbitan monostearate (20E.0.) 1.0 Polyoxyethylene sorbit monostearate (60E.0.) 0.5 Lipophilic monostearic acid Glycerin 1.0 Stearic acid 0.5 Behenyl alcohol 0.5 Poppy oil 0.5 Ultraviolet scattering agent (used in Example 4) 1.0 Ultraviolet scattering agent (used in Example 9) 0. 5 Sesame oil 2.0 Glyceryl trioctanoate 4.0 Lauric acid Polyoxyethylene hydrogenated castor oil (60E.0.) 0.5 B Kojic acid 0.5 1,3-butylene glycol 5.0 Methyl paraben 0.2 Polyvinyl alcohol ( PVA) 0.05 Carrageenan 0.15 Purified water A component belonging to an appropriate amount A is heated and dissolved. Separately, the components belonging to B are dissolved by heating. B was added to A, stirred, emulsified, and cooled to produce an emulsion. <Formulation Example 3> Lotion (% by weight) Polyoxyethylene hydrogenated castor oil (60E.0.0.) 8.0 Ethanol 15.0 Carrageenan 0.08 Quince seed extract 1.0 Ultraviolet scattering agent (Example 5) 0.5 Kojic acid glucoside 0.1 Kojic acid 0.5 Ethyl paraben 0.1 Citric acid 0.1 Sodium citrate 0.3 1,3-butylene glycol 4.0 Disodium edetate 0. 01 Purified water qs The above components were mixed, uniformly stirred and dissolved to produce a lotion. <Formulation Example 4> Cream pack (% by weight) A Vegum 5.0 Squalane 2.0 Polyvinylpyrrolidone (PVP) 2.0 Methylcellulose 0.5 Carrageenan 0.5 Sakaki oil 0.2 Ultraviolet scattering agent (Example 2.0) Kojic acid 0.5 Propylene glycol 5.0 Vitamin B ₁₂ 0.05 Purified water qs B zinc oxide 10.0 C Ethanol 5.0 A Swell and add B little by little. C was gradually added thereto and kneaded until a paste was obtained, thereby producing a cream pack. Formulation Example 5 Essence (% by weight) 1% carboxyvinyl polymer solution 10.0 Glycerin 20.0 Hyaluronic acid 0.5 Polyvinyl alcohol (PVA) 1.0 Carrageenan 0.5 Quinseed extract 2.0 Ultraviolet light Scattering agent (used in Example 7) 0.05 Kojic acid 2.0 Ethanol 1.0 Polyoxyethylene hydrogenated castor oil (60E.0.) 1.0 Purified water Appropriate amount Mix and homogenize each of the above components The mixture was stirred and dissolved to produce an essence. <Formulation Example 6> Gel (weight%) A Polyvinyl alcohol (PVA) 2.5 Polyvinylpyrrolidone (PVP) 1.0 Carrageenan 1.0 Polyoxyethylene hydrogenated castor oil (100E.0.0.) 3.0 Methylparaben 0.01 Cottonseed oil 0.05 B Ethanol 40.0 C Purified water qs D Kojic acid 1.0 Disodium edetate 0.01 Ultraviolet scattering agent (used in Example 8) 0.7 A to B Add and disperse, add C little by little and stir. Further, D is added little by little, mixed and stirred uniformly,
A gel was produced. <Formulation Example 7> Poultice (weight%) A polyacrylic acid 30.0 sorbitan monooleate 1.0 suitable amount of purified water B sodium polyacrylate 7.0 peanut oil 0.5 almond oil 3.5 Aluminum chloride 0.3 Concentrated glycerin 20.0 Ultraviolet scattering agent (used in Example 13) 4.0 A component belonging to 4.0 A is heated and dissolved. Separately, the components belonging to B are dissolved by heating. Add B to A and stir and mix. After cooling, it was applied to a coating agent to produce a poultice. The preparations of Formulation Examples 1 to 7 also had the same effect as the cream of the present invention shown in the examples. According to the present invention, a kojic acid and / or a kojic acid derivative is coated with a first coating agent comprising a specific compound, and the ultraviolet scattering agent is treated with a second coating agent . Interface which is two coating agent
By combining the activator with alcohol attached as an auxiliary , instantaneous coloring of kojic acids is eliminated, and the color of the ultraviolet scattering agent, stable dispersing over time without dispersibility reduction and caking phenomenon do not occur. Topical skin preparation with good usability
Is provided .

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-64-83008 (JP, A) JP-A-63-188609 (JP, A) JP-A-62-108804 (JP, A) JP-A-4- 352708 (JP, A) JP-A-4-18010 (JP, A) JP-A-4-9310 (JP, A) JP-A-5-221841 (JP, A) JP-A-5-238926 (JP, A) JP-A-5-25019 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K ^7/ 00-7/50

Claims (1)

(57) [Claim 1] Kojic acid and / or a derivative thereof ,
Sodium arate, aluminum stearate, iso
Stearic acid, magnesium myristate, myristine
Isolate, zinc palmitate and oleic acid
An ultraviolet scattering agent coated with a first coating agent selected from the group consisting of oleyl , a surfactant as a second coating agent
An external preparation for skin, characterized by containing, as an active ingredient, a substance obtained by adhering to an alcohol as an auxiliary agent.