JP2001151635A - Oil-in-water type emulsion preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oil-in-water type emulsion preparation for external use for skin that has excellent storage stability. SOLUTION: This oil-in-water type emulsion preparation for external use for skin comprises (a) laminar silicate mineral, (b) an oil-soluble medicine with an 10B value of 0.1-2 and (c) a water-soluble high-molecular-weight polymer.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a layered silicate and a water-soluble polymer for determining the storage stability of an O / W preparation containing an oil-soluble drug, especially a polar oil-soluble drug, especially at high temperatures. And an oil-in-water emulsified skin external preparation improved by incorporating

2. Description of the Related Art In the preparation of an emulsified pharmaceutical preparation, the interaction between a drug and a surfactant (emulsifier) is liable to occur due to the large amount of the active ingredient, making it difficult to emulsify and impairing the stability of the preparation. There were many. In particular, for oil-soluble drugs, it is difficult to stabilize the preparation using only a surfactant. Therefore, various emulsification methods have been considered for stabilization. Examples thereof include a phase inversion emulsification method and Japanese Patent Publication No. Sho 60-251.
No. 83, a sugar ester method, a D-phase emulsification method, and the like. However, in the phase inversion emulsification, the sugar ester method and the D-phase emulsification method, the oil-soluble drug that can be emulsified is limited to a low-polarity one. In addition, the compounding of highly polar oil-soluble drugs is limited, such as causing gel breakage, making it difficult to form a liquid crystal structure, and requiring a large amount of a surfactant. As described above, oil-soluble drugs, particularly oil-soluble drugs having high polarity, are said to adversely affect emulsification. For example, the oil-soluble drugs crotamiton and diphenhydramine have excellent affinity for the skin and have a strong antipruritic effect, and are therefore excellent drugs in external preparations for the skin. However, since oil-soluble drugs adversely affect the emulsified preparation as described above, development of a stable emulsified skin external preparation containing such a drug has been desired. Japanese Patent Application Laid-Open No. Hei 3-20227 describes an external preparation for skin in which the use of a clay mineral and a drug is combined to improve drug release, transdermal absorption, and feeling of use. In particular, storage stability at high temperatures is not satisfactory.

[0002]

SUMMARY OF THE INVENTION An object of the present invention is to provide an oil-in-water emulsified skin external preparation containing an oil-soluble drug which has excellent storage stability.

The present invention comprises: a) a layered silicate mineral, b) an oil-soluble drug having an IOB value of 0.1 to 2,
c) An oil-in-water emulsified skin external preparation characterized by containing a water-soluble polymer is provided.

DETAILED DESCRIPTION OF THE INVENTION a) The layered silicate mineral of the present invention comprises:
It is a substance having an action of stably emulsifying an oil-soluble drug in the external preparation for skin of the present invention. Such layered silicate minerals include kaolinite group (kaolinite), pyrophyllite group (pyrophyllite), talc group (talc),
Smectites (montmorillonite, beidellite, hectorite, saponite, sauconite, stevensite), mica (muscobite, sericite) and the like can be mentioned. Substances based on the above minerals can also be used. For example, kaolin based on kaolinite, bentonite based on montmorillonite, aluminum silicate and acid clay, aluminum magnesium silicate based on saponite, mica based on muscobite and sericite, etc. No.
Among these, bentonite, aluminum magnesium silicate, acid clay, and mica are preferred. These can be used alone or in combination of two or more. The amount of the layered silicate mineral is preferably 0.01 to 10% by mass, more preferably 0.5 to 5% by mass, based on the total mass of the present invention.

[0003] The oil-soluble drug which is the component b) of the present invention is represented by I
It is a polar oil-soluble drug having an OB value of 0.1 to 2. Here, the IOB value is a numerical value (I) obtained from the inorganic value (IV) and the organic value (OV) of the functional group of the compound.
OB value = IV / OV), and the larger the value, the higher the polarity. When the IOB value is within the above range, the drug is highly effective and is preferably present in the oil phase stably. Preferably, the IOB value is 0.2 to 2, more preferably 0.3 to 1.5. Specifically, crotamiton and the like can be mentioned as antipruritic agents. Examples of anti-inflammatory agents include glycyrrhetinic acid and its salts, cortisone, hydrocortisone, prednisolone, dexamethasone, indomethacin, ketoprofen, suprofen, piroxicam, bufexamac, felbinac, ufenamate and the like. Examples of the local anesthetic include, but are not limited to, lidocaine, dibucaine, diphenhydramine, and the like. Of these, crotamiton, diphenhydramine and glycyrrhetinic acid are preferred. These can be used alone or in combination of two or more. The compounding amount of the component (b) is a sufficient amount to exhibit a medicinal effect based on the total mass of the present invention, preferably 0.01 to 20% by mass, more preferably 0.1 to 10% by mass.

[0004] The water-soluble polymer (c) of the present invention is a substance having an action of expanding the interlayer of the layered silicate mineral. Such a water-soluble polymer preferably has an average molecular weight of 100 to 5
Million, more preferably 1,000 to 1,000,000, specifically, carboxyvinyl polymer, xanthan gum, hydroxyethylcellulose, methylcellulose,
Carrageenan, sodium alginate, gum arabic,
Guar gum, locust bean gum, pullulan, gelatin, sodium polyacrylate, sodium carboxymethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol and the like can be mentioned, but are not limited thereto. Among these, xanthan gum, polyethylene glycol and carboxyvinyl polymer are preferred. These water-soluble polymers can be used alone or in combination of two or more. The compounding amount of the water-soluble polymer of the component c) is preferably 0.01 to 5% by mass, more preferably 0.05 to 3%, and more preferably 0.05 to 2% by mass based on the total mass of the present invention. Particularly preferred.

[0005] The present invention usually contains a surfactant, an oily base and water in addition to the oil-soluble medicinal ingredient. The surfactant is preferably a nonionic surfactant that is usually used as an O / W emulsifier. Specifically, polyoxyethylene alkyl ether, ether compounds such as polyoxyethylene polypropylene alkyl ether, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, Polyethylene glycol fatty acid esters,
Examples include ester compounds such as sucrose fatty acid esters, polyoxyethylene castor oil / hardened castor oil, and polyoxyethylene polyoxypropylene polymers. Among them, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester,
Polyethylene glycol fatty acid esters, polyoxyethylene castor oil and hydrogenated castor oil are preferred. They are,
They can be used alone or in combination of two or more. The compounding amount of the surfactant is preferably from 1 to 15% by mass, more preferably from 5 to 15% by mass, based on the total mass of the present invention.

Examples of the oily base used in the present invention include hydrocarbons such as squalane, liquid paraffin, petrolatum, and microcrystalline wax; silicone oils such as methylpolysiloxane, methylphenylpolysiloxane, and dimethylcyclopolysiloxane; Waxes such as beeswax, higher alcohols such as cetyl alcohol, stearyl alcohol and cetostearyl alcohol, sterols such as cholesterol, octyl dodecyl oleate, oleyl oleate, cetyl octanoate, fatty acids such as isopropyl myristate and myristyl myristate Examples include esters, metal soaps such as aluminum stearate, magnesium stearate and the like. Of these, squalane, petrolatum, methylpolysiloxane, beeswax,
Cetyl alcohol is preferred. These can be used alone or 2
More than one type can be used in combination. The compounding amount of the oily base is preferably from 1 to 80% by mass, more preferably from 10 to 70% by mass, based on the total mass of the present invention. This range is preferable because emulsification is easy and the usability is good. The W / O emulsified composition of the present invention may contain, in addition to the above components, a nonionic surfactant, an oily base, an aqueous base, a water-soluble component, and vitamins, which may be added to a normal skin external preparation, if necessary. , Antioxidants, chelating agents, preservatives, fresheners,
A pH adjuster or the like can be blended.

Examples of the aqueous base include lower alcohols such as ethanol, propyl alcohol and isopropyl alcohol, polyhydric alcohols such as glycerin, glycols such as ethylene glycol, propylene glycol and butylene glycol, sucrose, lactose, maltose, mannitol, and the like. Saccharides such as erythritol and xylitol, and sugar alcohols. Examples of water-soluble components include natural moisturizing components (NMF) such as urea, amino acids, sodium pyrrolidonecarboxylate, and sodium lactate; hyaluronic acid;
Heparin-like substances, mucopolysaccharides such as chondroitin sulfate, and water-soluble vitamins such as collagen and pyridoxine hydrochloride. Vitamins include tocopherol, tocopherol acetate, palmitic acid, retinol,
Examples thereof include oil-soluble vitamins such as vitamin A oil and water-soluble vitamins such as pyridoxine hydrochloride. Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, ascorbic acid and the like. Examples of the chelating agent include disodium edetate, ethylenediaminetetraacetate, pyrophosphate, hexametaphosphate, and gluconate. As preservatives, parabens,
Examples include benzoates and benzalkonium chloride.

Examples of the cooling agent include menthol, camphor, cauliflower oil and the like. Examples of the pH adjuster include sodium hydroxide, potassium hydroxide, triethanolamine, boric acid, citric acid, lactic acid, and potassium hydrogen phosphate. The blending amount of each optional component is preferably 0.01 to 50% by mass, more preferably 0.1 to 30% by mass of the whole emulsion of the present invention. The external preparation for skin of the present invention is an oil-in-water emulsion, but the oil phase / water phase ratio is 5 / 95-
60/40 (mass ratio) is preferred, and 10 / 90-50 /
50 is more preferred, and 15/85 to 30/70 is even more preferred. When the oil phase / water phase ratio is within this range, a preparation having good stability can be obtained, which is preferable. The external preparation for skin of the present invention can be used as pharmaceuticals, quasi-drugs, and cosmetics, and the dosage form can be arbitrarily selected according to the purpose, and is in the form of cream, ointment, emulsion, or pack. , A stick shape or the like. The skin external preparation which is the oil-in-water emulsion of the present invention can be prepared by a conventional method.

[0009]

EXAMPLES O / W emulsions were prepared with the compositions of Examples and Comparative Examples shown in Tables 1 to 9 below, and the storage stability in each temperature range was evaluated. (Preparation method) A water phase and an oil phase are individually prepared, and
The mixture was heated and stirred at a temperature of from 70 ° C. to 70 ° C. and uniformly dissolved. 60 ° C ~
5000 rpm using a homomixer at a temperature of 70 ° C.
While stirring the aqueous phase at ６6000 rpm, the oil phase was slowly added and emulsified for 5 to 10 minutes to obtain an O / W emulsion. (Stability) The storage stability was evaluated by placing the prepared emulsion in a sample tube with a screw cap, storing the emulsion under predetermined conditions, and observing the state. The stability was evaluated according to the following five grades, and △ was regarded as a stable level. Storage stability: no change: 、, slightly reduced viscosity: 、, reduced viscosity: Δ, slightly exuded oil on the surface: ▲, phase separation: ×

[0010]

[Table 1]

[0011]

[Table 2]

[0012]

[Table 3]

[0013]

[Table 4]

[0014]

[Table 5]

[0015]

[Table 6]

[0016]

[Table 7]

[0017]

[Table 8]

[0018]

[Table 9] Regarding Examples 21 to 24, external preparations of the present invention in various dosage forms were prepared according to the above-mentioned preparation methods, and the storage stability was evaluated under the above-mentioned conditions.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C083 AA082 AB032 AB371 AB382 AB432 AB442 AC012 AC022 AC072 AC122 AC182 AC302 AC392 AC422 AC432 AC442 AC482 AC512 AC532 AC542 AC552 AC642 AC852 AD042 AD092 AD152 AD282 AD352 AD492 AD532 AD662 BB36 CC02 CC05 DD22 DD33 EE12

Claims (2)

[Claims] 1. An oil-in-water type emulsified skin external preparation comprising: a) a layered silicate mineral; b) an oil-soluble drug having an IOB value of 0.1 to 2; c) a water-soluble polymer. 2. A method for stabilizing an oil-in-water emulsion containing an oil-soluble polar drug, comprising blending a layered silicate and a water-soluble polymer as a stabilizer.