KR20100044094A - EXTERNAL COMPOSITION CONTAINING γ-ORYZANOL - Google Patents

Abstract

PURPOSE: An external use composition containing gamma-oryzanol is provided to prevent discoloration for a long time and enhance product value. CONSTITUTION: An external use composition contains 0.01-5 mass% of gamma-oryzanol, phosphoric acid or salt or solvate or Vaseline thereof. The gamma-oryzanol in contained in rice oil, rice embryo oil, and bran oil of other cereal. The phosphoric acid is orthophosphoric acid, pyrophosphate or polyphosphoric acid. The content of Vaseline is 1-45 mass% based on total mass. The Vaseline is white or yellow Vaseline containing moisturizer.

Description

γ-orizanol-containing external preparation composition {EXTERNAL COMPOSITION CONTAINING γ-ORYZANOL}

The present invention relates to a γ-orizanol-containing external preparation composition in which discoloration over time is suppressed.

γ-orizanol is a substance present in rice bran oil, rice germ oil, corn oil, and other cereal oils. It is a ferulic acid (3-methoxy-4-hydroxy cinnamic acid) of triterpene alcohol. ) It is a mixture of ester (nonpatent literature 1). The pharmacological action of γ-orizanol has been reported in various ways, such as growth promoting action, alleviation of autonomic ataxia, gonadotropin, sebum secretion promoting action, blood flow promoting action, skin temperature raising action, antioxidant action, UV-absorbing activity, tyrosinase activity inhibitory effect, etc., and also a high safety substance. Therefore, it has been applied to pharmaceuticals, cosmetics, food additives, and even animal growth promoters, and has been widely used. For example, as a skin external preparation containing γ-orizanol, a skin external preparation comprising urea and purified γ-orizanol is known (Patent Document 1).

Moreover, since gamma-orizanol is fat-soluble, various examinations are made at the time of formulation, and the technique of supplying it in the form of aqueous solution is also known (patent document 2).

Patent Document 1: Japanese Patent No. 3493459

Patent Document 2: Japanese Patent Application Laid-Open No. 07-258165

Non-Patent Document 1: FRAGRANCE JOURNAL, 3, p71-77, 1998

(gamma) -orizanol is fat-soluble, and it is advantageous to dissolve in an oil phase and apply it to skin etc. in the form of an emulsion composition, an oily ointment, etc. from the point of water absorption, stability, etc. However, when preparing the external preparation composition containing (gamma) -orizanol, when it mix | blended (gamma) -orizanol in an oil phase, it turned out that the problem that the oil phase obtained turns yellow with time. Discoloration of the external preparation composition greatly reduces the product value.

Therefore, an object of this invention is to provide the external preparation composition which suppresses discoloration over time in which (gamma) -orizanol is contained in an oil phase.

Therefore, the present inventors have made various studies on the inhibition of discoloration over time of the external preparation composition, and when phosphoric acid or its salt or a solvate thereof, or petrolatum, are individually formulated into a γ-orizanol-containing external preparation composition, Although the inhibitory effect of discoloration over time of the external preparation composition was not seen, it was surprisingly found that a stable external preparation composition was obtained without causing discoloration specifically for a long time only when it was combined and combined, and thus, the present invention was completed.

That is, this invention provides the external preparation composition containing (gamma) -orizanol, phosphoric acid or its salt or solvate, and petrolatum.

According to the present invention, it is possible to provide an external preparation composition such as a skin or mucosal external preparation or suppository containing γ-orizanol having various pharmacological and physiological effects in the oil phase, which is stable without prolonged discoloration, and has high merchandise value. Can be.

"(Gamma) -orizanol" is obtained from the seed of rice (Oryza sativa L.), etc., and mainly consists of a ferulic acid (3-methoxy-4-hydroxy cinnamic acid) ester of triterpene alcohol, As "(gamma) -orizanol" used, a raw material, a purification method, a manufacturing method, etc. are not specifically limited, The gamma-orizanol of the quasi-drug quasi-drug raw material specification 2006 is preferable. In this invention, a commercial item can be used as (gamma)-oryzanol, As a commercial item, for example, (gamma) -orizanol "riken" (made by Riken vitamin company), (gamma) -orizanol (made by Orija emulsification company), and oranol-C (Made by Okayasu store company), etc. are mentioned.

As for content of (gamma) -orizanol in the external preparation composition of this invention, 0.01-5 mass% is preferable with respect to the total mass of an external preparation composition from a viewpoint of a pharmacological effect, a physiological effect, and the suppression effect of time-dependent discoloration of an external preparation composition, and 0.1 -3 mass% is more preferable, and 0.5-2 mass% is especially preferable. In addition, content of (gamma) -orizanol can be quantified by HPLC method (UV detection), for example.

As the "phosphoric acid or salts thereof or solvates thereof" used in the present invention, in addition to phosphoric acid itself, salts thereof (for example, alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts) and the solvents thereof A cargo (for example, a hydrate) is mentioned, These 1 type or 2 or more types can be used in combination.

As a specific example of phosphoric acid, orthophosphoric acid, pyrophosphoric acid, polyphosphoric acid, etc. are mentioned, for example.

As a specific example of a phosphate salt, For example, Phosphates, such as a trisodium phosphate, a tripotassium phosphate, a triammonium phosphate; Dihydrogen phosphates, such as sodium dihydrogen phosphate, potassium dihydrogen phosphate, ammonium dihydrogen phosphate, and calcium dihydrogen phosphate; Hydrogen phosphates such as sodium dihydrogen phosphate, potassium dihydrogen phosphate, diammonium hydrogen phosphate, calcium hydrogen phosphate and the like.

As a specific example of the solvate of phosphoric acid or its salt, phosphate hydrates, such as sodium monohydrogen phosphate hydrate, calcium hydrogen phosphate monohydrate, sodium dihydrogen phosphate monohydrate, dicalcium phosphate dihydrate, etc. are mentioned, for example.

Among them, in the present invention, orthophosphoric acid or salts thereof or solvates thereof are preferable from the viewpoint of the effect of suppressing discoloration over time of the external preparation composition, the dihydrogen salt of orthophosphoric acid or solvate thereof is more preferable, and phosphoric acid Potassium dihydrogen is particularly preferred.

In this invention, a commercial item can be used as phosphoric acid or its salt, or those solvates, As these commercial items, for example, 1 sodium phosphate (manufactured by Wako Junyakusa), 2 sodium hydrogen phosphate (manufactured by Wako Junyakusa), phosphoric anhydride Sodium dihydrogen (manufactured by Taihei Chemical Industry Co., Ltd.), potassium dihydrogen phosphate (manufactured by Kanto Chemical Co., Ltd., manufactured by Wako Pure Chemical Industries, Ltd.), potassium hydrogen phosphate (manufactured by Wako Pure Chemical Industries, Ltd.), and the like.

The content of phosphoric acid or salts thereof or solvates thereof is based on the mass of free phosphoric acid (salts such as orthophosphoric acid, pyrophosphoric acid, polyphosphoric acid, etc.) with respect to the total mass of the external composition, from the viewpoint of the effect of suppressing discoloration of the external composition over time. In the solvate, 0.01-5 mass% is preferable, 0.02-4 mass% is more preferable, and 0.03-3 mass% respectively, converting into the corresponding mass of free bodies, such as orthophosphoric acid, pyrophosphoric acid, and polyphosphoric acid), respectively. Is particularly preferred.

The content ratio of γ-orizanol and phosphoric acid or salts thereof or solvates thereof is 0.01 to 1 part by mass in terms of free phosphoric acid relative to 1 part by mass of γ-orizanol from the viewpoint of the effect of suppressing discoloration over time of the external preparation composition. 5 mass parts is preferable, 0.02-4 mass parts is more preferable, 0.03-3 mass parts is especially preferable.

"Vaseline" used in the present invention mainly includes white petrolatum, yellow petrolatum, and the like as a component to be blended as a moisturizing agent and a base. In this invention, white petrolatum is preferable from a viewpoint of the inhibitory effect of the discoloration over time of an external preparation composition, and the white petrolatum of 15th revision Japanese pharmacy room is especially preferable.

The content of petrolatum is preferably 1 to 45% by mass, more preferably 1.5 to 40% by mass, particularly preferably 2 to 35% by mass with respect to the total mass of the external preparation composition from the viewpoint of the effect of suppressing discoloration over time.

As for the content ratio of (gamma) -orizanol and petroleum jelly, 1-45 mass parts is preferable with respect to 1 mass part of (gamma) -orizanol from a viewpoint of the inhibitory effect of the discoloration over time of an external preparation composition, and 1.5-40 mass parts is more preferable , 2 to 35 parts by mass are particularly preferred.

In addition, the content ratio of phosphoric acid or its salts or solvates thereof and petroleum is 0.2 to 4500 parts by mass based on 1 part by mass of phosphoric acid converted into the mass of free phosphoric acid from the viewpoint of the effect of suppressing discoloration over time of the external preparation composition. It is preferable, 0.2-2000 mass parts is more preferable, 0.6-1500 mass parts is especially preferable.

As an oil-based component in the external preparation composition of this invention, if it is generally used as a component which comprises an oil phase in external preparation compositions, such as an emulsion composition and an oily ointment composition, it will not specifically limit, For example, hydrocarbons (flow paraffin, squalane) Waxes (bleached wax, carnauba wax, candelilla wax, lanolin, etc.), fats and oils (soybean oil, hardened fat, castor oil, olive oil, triacylglycerol, etc.), alcohols (cetanol, Stearyl alcohol, oleyl alcohol, cholesterol, etc.), fatty acids (such as palmitic acid, stearic acid, oleic acid), silicone oils (such as methyl polysiloxane), vitamin derivatives (retinol, tocopherol acetate, etc.) These can be used individually or in combination of 2 or more types. It is preferable to contain 1-1000 mass parts of these oily components with respect to 1 mass part of (gamma)-oryzanol in the external composition of this invention from the solubility of (gamma)-oryzanol, and it is more preferable to contain 5-500 mass parts It is preferable and it is especially preferable to contain 7.5-200 mass parts.

The external preparation composition of this invention can contain an emulsifier, an aqueous component, a preservative, antioxidant, another active ingredient, water, etc. as needed in accordance with various conditions, such as the purpose and form of use of an external preparation composition, in addition to the said component.

As an emulsifier, For example, polyoxyethylene alkyl ether (polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, etc.), polyoxyethylene alkyl phenyl ether (polyoxy ethylene nonyl phenyl ether, polyoxyethylene octyl phenyl ether, etc.) , Polyoxyethylene polyoxypropylene alkyl ether (polyoxyethylene polyoxypropylene cetyl ether, etc.), polyoxyethylene sorbitan fatty acid ester (monolauric acid polyoxyethylene sorbitan, etc.), polyoxyethylene sorbitan fatty acid ester (mono) Oleic acid polyoxyethylene sorbitan, monostearate polyoxyethylene sorbitan (polysorbate 60), tristearate polyoxyethylene sorbitan, etc.), polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene sorbent Beet wax, sucrose fatty acid ester, monoacylglycerol (glycerol monostearate, etc.) ), Diacylglycerol (such as glyceryl distearate), polyglycerol fatty acid ester (such as diglyceryl monostearate), polyoxyethylene lanolin, polyoxyethylene lanolin alcohol, polyoxyethylene sterol, polyoxyethylene fatty acid amide (poly Oxyethylene stearate and the like), lecithin, polyethylene glycol fatty acid esters (such as polyethylene glycol monolaurate), propylene glycol fatty acid esters (such as propylene glycol monostearate), sorbitan fatty acid esters (such as sorbitan monostearate), Alkyl sodium sulfate (such as sodium lauryl sulfate) etc. can be mentioned, These can be used individually or in combination of 2 or more types.

It is preferable that these emulsifiers contain 0.5-10 mass% in the external composition of this invention from the viewpoint of the solubility of (gamma) -orixanol, the irritation to skin, etc., and it is more preferable to contain 1-5 mass%, 1.5-4 It is especially preferable to contain mass%.

As the aqueous component, for example, lower alcohols (ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, glycerin, propylene glycol, polyethylene glycol, etc.), water-soluble polymers (methyl cellulose, ethyl Cellulose, carboxyvinyl polymer, xanthan gum, polyvinylpyrrolidone, water-soluble collagen, hyaluronic acid, etc.), amino acids (glycine, alanine, etc.), and others (citric acid, lactic acid, sodium lactate, sodium chloride, etc.). These can be used individually or in combination of 2 or more types.

As a preservative, methyl paraben, propyl paraben, butyl paraben, etc. are mentioned, for example, These can be used individually or in combination of 2 or more types.

As antioxidant, edetate salt, such as sodium edetate hydrate or its hydrate, dibutyl hydroxytoluene, tocopherol, etc. are mentioned, for example. In addition, these can be used individually or in combination of 2 or more types.

As other medicinal ingredients, for example, for the purpose of ginseng, antihistamines (diphenhydramine, chloro malelate, etc.), local anesthetics (ethylaminobenzoate, lidocaine and the like), topical anti-inflammatory antitussives ( Camphor, menthol and the like), and others (crotamitone, glytiretinic acid and the like) and the like can be blended, and these can be used alone or in combination of two or more thereof. For the purpose of moisturizing, polyhydric alcohols (1,3-butylene glycol, glycerin, propylene glycol, polyethylene glycol, etc.), amino acids (glycine, alanine, etc.), acidic mucopolysaccharides (hyaluronic acid, heparin-like substances, etc.) And sugar alcohols (sorbitol, trehalose, etc.), and others (urea, lactic acid, sodium lactate, pyrrolidone carboxylate, etc.) and the like can be blended, and these can be used alone or in combination of two or more thereof.

4-9 are preferable and, as for pH of the external preparation composition of this invention, in terms of stability of (gamma) -orixanol and the irritation of an external preparation composition, 5-8 are more preferable. In addition, the pH may be adjusted in accordance with a conventional method using sodium hydroxide or the like.

2 g-50 g are preferable and, as for the roughness of the external preparation composition of this invention, 5 g-45 g are more preferable. The illuminance represents the maximum value of the stress when a metal ball 1 cm in diameter enters 1 cm at a speed of 6 cm / min at 25 ° C., and can be measured by a rheometer (FUDOH Rheometer: Leotec Co., Ltd.). .

The external preparation composition of the present invention may contain γ-orizanol in an oil phase, and may be, for example, an emulsion composition or an oily ointment composition. An emulsion composition, in particular, an oil-in-water emulsion composition, is preferable from the viewpoint of usability and the like. As a preferable form of an emulsion composition, cream, emulsion, lotion, etc. are mentioned.

In the case where the external preparation composition of the present invention is an emulsion composition, the mass ratio of the oil phase / water phase is preferably from 0.05 to 1/1, more preferably from 0.1 to 0.95 / 1, from the viewpoint of emulsion stability.

The external preparation composition of this invention can be manufactured according to a conventional method, and can be manufactured similarly to a conventional emulsion composition, ointment, etc. For example, an aqueous phase in which phosphoric acid or a salt thereof or a solvate thereof is dissolved, and an oil phase in which γ-orizanol and petrolatum are dissolved are heated and mixed, and then emulsified under heating conditions such as 50 to 80 ° C, followed by cooling. have.

As a use form of the external preparation composition of this invention, application | coating to a skin area | region or mucous membrane, or infusion | pouring into the anus as suppository, etc. are mentioned, for example, application | coating to skin area is preferable.

Example

Next, although an Example is given and this invention is demonstrated in more detail, this invention is not limited to this at all.

Example 1

Potassium dihydrogen phosphate (potassium dihydrogen phosphate: manufactured by Kanto Chemical Co., Ltd.) 0.5 g, urea 20 g, and sodium hydroxide equivalent to an amount of pH 7.2 of the cream are added to purified water corresponding to an amount of 100 g of the total amount of cream. It added, and made into the water phase what heated and mixed at 75 degreeC. On the other hand, 1 g of γ-orizanol (Orizanol-C: manufactured by Okayasu Co., Ltd.), 15 g of white petrolatum (white petrolatum: manufactured by Sonneborn), 0.3 g of glyctylenic acid, 6 g of squalane, and 1.2 g of monostearate , 1.4 g of polysorbate 60 and 50 0.5 g of polyoxyethylene-cured castor oil were added to the mixture, which was heated and mixed at 75 ° C. to obtain an oil phase. An oil phase was added to the aqueous phase, stirred and mixed at 75 ° C, emulsified, cooled to room temperature, and 100 g of a total amount of cream was prepared. The cream obtained was white.

Comparative Example 1

In the same manner as in Example 1, except that potassium dihydrogen phosphate was not added in Example 1, it was prepared as a cream of Comparative Example 1. The cream obtained was white.

Comparative Example 2

The thing which did not mix | blend white petroleum jelly in Example 1 was produced like cream of the comparative example 2 except having not mix | blended white petroleum jelly. The cream obtained was white.

Test Example 1

About the cream prepared in Example 1 and Comparative Examples 1 and 2, the following evaluation items were evaluated.

(Evaluation of discoloration inhibition over time)

Discoloration evaluated visually the change of the color tone of the cream after 40 degreeC and 6-month dark storage with respect to the color tone immediately after preparation. (Circle) and the thing discolored to yellow to brown were made into those with no change in color tone. In addition, pH of the cream after 40 degreeC and 6-month dark storage was measured.

The test results are shown in Table 1.

As can be seen from Table 1, discoloration over time was suppressed only when the potassium dihydrogen phosphate and petrolatum were blended into the cream containing γ-orizanol. From the test results, it has been found that the external preparation composition of the present invention containing γ-orizanol, phosphoric acid or its salt or solvate thereof, and petrolatum is a stable external preparation composition without discoloring for a long time.

Example 2

Potassium dihydrogen phosphate (potassium dihydrogen phosphate: manufactured by Kanto Chemical Co., Ltd.) 0.8 kg, urea 32 kg, glycine 4.8 kg, sodium hydroxide 0.16 kg, sodium edetate hydrate 0.01 kg and purified water 70 kg were charged to an aqueous kiln, at 75 ° C. It melt | dissolved in heating and made it an aqueous phase. Meanwhile, 1.6 kg of gamma -orizanol (Orizanol-C: manufactured by Okayasu Co., Ltd.), 28.8 kg of white petrolatum (white petrolatum: manufactured by Sonneborn), 0.8 kg of glyctylenic acid, 9.6 kg of liquid paraffin, 3.2 kg of cetanol, 3.2 kg of stearyl alcohol, 1.6 kg of glycerin monostearate, 1.76 kg of polysorbate 60, and 1.76 kg of polyoxyethylene-cured castor oil were added to an oily kiln, and heated and mixed at 75 ° C to obtain an oil phase. The oil phase and the water phase were put in an emulsifying kiln, emulsified and mixed at 75 ° C for 10 minutes, and cooled after stirring, further stirring to prepare a total amount of cream of about 160 kg.

Claims (2)

The external preparation composition containing (gamma) -orizanol, phosphoric acid or its salt, or solvate, and petrolatum. The method of claim 1 The external preparation composition whose phosphoric acid or its salt, or their solvate is potassium dihydrogen phosphate.