JP2001181166A - Water-in-oil type emulsified skin care composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a water-in-oil type emulsified skin care composition which shows excellent storage stability and contains an oil-soluble drug. SOLUTION: This water-in-oil type emulsified skin care composition is obtained by including (a) an oil-soluble drug with an IOB value of 0.1-2 and (b) a lipophilic emulsifier bearing at least two of hydrophobic groups containing a hydrocarbon chain with carbon numbers of more than 8 in the molecule.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a water-in-oil emulsified skin external preparation composition containing a highly polar oil-soluble drug.

2. Description of the Related Art Water-in-oil (W / O) emulsions provide skin protection and flexibility, compared to oil-in-water (O / W) emulsions.
It is excellent in many aspects such as suppression of moisture vapor emission and resistance to bacteria, and is considered to be a dosage form suitable for, for example, dry skin. If a drug is blended with such a W / O emulsion, a therapeutic agent having an excellent therapeutic effect can be expected. However, W / O emulsions have poorer formulation stability than O / W emulsions, and are stable over a wide temperature range.
It was difficult to obtain an / O emulsion. In particular, when a polar oil-soluble drug such as crotamiton or diphenhydramine is added, it has been difficult to maintain the stability of the W / O emulsion. This is presumed to be because the polar compound is poorly compatible with the lipophilic group of the surfactant, destabilizes the W / O emulsion, and tends to cause component separation. In particular, crotamiton and diphenhydramine have a remarkable tendency to make such W / O unstable. That is, although a W / O emulsion containing a polar oil-soluble drug can be expected to have a high therapeutic effect, it is difficult to form a stable formulation, and it has been desired to solve the problem.

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

SUMMARY OF THE INVENTION Accordingly, the present inventors have remedied such drawbacks of the prior art and have developed a large number of surfactants in order to obtain a W / O emulsion which is stable even if it contains a highly polar oil-soluble drug. As a result of intensive studies, a lipophilic emulsifier having excellent storage stability was found. That is, the present invention provides (a) an oil-soluble drug having an IOB value of 0.1 to 2,
(B) a water-in-oil type emulsified skin external preparation characterized by containing a lipophilic emulsifier having two or more hydrophobic groups containing a hydrocarbon chain having 8 or more carbon atoms in a molecule.

[0002]

BEST MODE FOR CARRYING OUT THE INVENTION Component (a) In the present specification, the IOB value means an inorganic value (IV) and an organic value (O) of a functional group of a compound in an organic conceptual diagram.
V) (IOB value = IV / OV), and the larger the value, the higher the polarity.
Examples of oil-soluble drugs having an IOB value of 0.1 to 2 include antipruritic agents such as crotamiton (0.585), glycyrrhetinic acid (0.678) and its salts, anticorrosives, hydrocortisone (1.22), prednisolone (1.22), Dexamethasone (1.06), indomethacin (0.79), ketoprofen (0.764), suprofen (0.825), piroxicam (0.
941), bufexamac (1.40), felbinac (0.64)
3), Ufenamate (0.467) and the like, such as lidocaine (1.10), dibucaine (0.975) and diphenhydramine (0.353) which are local anesthetics. In addition,
The number in parentheses indicates the IOB value. Among them, those having an IOB value of 0.2 to 2 are preferable, and those having an IOB value of 0.3 to 1.5 are more preferable. These can be used alone or in combination of two or more. The amount of these compounds is not particularly limited, but in consideration of the purpose of the present invention, is an amount sufficient to exhibit a pharmacological effect, and is 0.01 to 0.01% based on the entire composition of the present invention. 20% by mass
, And more preferably 0.1 to 10% by mass.

Component (b) The component (b) used in the present invention is a lipophilic emulsifier having two or more hydrophobic groups containing a hydrocarbon chain having 8 or more carbon atoms, preferably 12 to 22 carbon atoms in the molecule. Examples of the hydrocarbon group include saturated, unsaturated, and cyclic hydrocarbons.These hydrocarbon groups may be substituted with an ester group or the like, and contain a hetero atom such as oxygen or nitrogen. Is also good. The two hydrophobic groups may be the same or different. Specifically, polyglyceryl pentaoleate, polyglyceryl pentastearate, polyglyceryl heptaoleate, polyglyceryl fatty acid esters such as polyglyceryl condensed ricinoleate, sorbitan sesquistearate, sorbitan tristearate, sorbitan sesquioleate, sorbitan trioleate Sorbitan fatty acid esters such as polyoxyethylene sorbitan tristearate, polyoxyethylene glycerin fatty acid esters such as polyoxyethylene glycerin tristearate, and polyoxyethylene sorbite such as polyoxyethylene sorbite tetraoleate. Fatty acid ester, polyoxyethylene sorbite beeswax, polyoxyethylene tristearate trimethylo Polyoxyethylene trimethylolpropane fatty acid ester such as propane, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil fatty acid ester such as triisostearate polyoxyethylene hydrogenated castor oil, polyoxyethylene cholesteryl ether , Lecithin derivatives,
N-acylglutamic acid esters such as lauroylglutamic acid dipolyoxyethylene stearyl ether, polyoxyethylene / methylpolysiloxane copolymer, poly (oxyethylene / oxypropylene) methylpolysiloxane copolymer, acrylic acid / alkyl methacrylate Polymers and the like can be mentioned, and one type or two or more types are selected from these and used. Particularly, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil fatty acid ester, polyoxyethylene cholesteryl ether, lecithin derivative, polyoxyethylene / methylpolysiloxane copolymer, poly (oxyethylene / oxypropylene) / methylpolysiloxane Copolymers and acrylic acid / alkyl methacrylate polymers are preferred.

The component (b) is preferably blended in an amount of 1 to 15% by mass, more preferably 5 to 10% by mass, based on the whole composition. When the amount is within this range, the composition can be easily emulsified, and there is no stickiness when applied to the skin, and the stability of the composition is also improved. The present invention is usually prepared by mixing the above components (a) and (b), an oily base and water, but by further mixing the following component (c), the composition of the present invention can be further prepared. This is preferable because the storage stability of the product is improved. (C) Component The (c) component used in the present invention is a lipophilic emulsifier having one hydrophobic group containing a hydrocarbon chain having 8 or more carbon atoms, preferably 12 to 22 in the molecule. As the hydrocarbon group,
Examples thereof include saturated, unsaturated and cyclic hydrocarbons. These hydrocarbon groups may be substituted with an ester group or the like, and may contain a hetero atom such as oxygen or nitrogen. The hydrophobic group of the component (c) may be the same as or different from one of the two hydrophobic groups of the component (b). Specifically, examples of the oil-soluble emulsifier having one hydrophobic group include:
Polyethylene glycol fatty acid esters such as polyethylene glycol monostearate, propylene glycol fatty acid esters such as propylene glycol monostearate, polyoxyethylene alkyl ethers such as polyoxyethylene cetyl ether and polyoxyethylene oleyl ether, and glycerin such as glycerin monostearate Fatty acid esters, propylene glycol fatty acid esters such as propylene glycol monostearate, polyoxyethylene alkylphenyl ethers such as polyoxyethylene nonylphenyl ether, polyoxyethylene polyoxypropylene alkyl ethers such as polyoxyethylene polyoxypropylene cetyl ether, etc. Can be mentioned. These emulsifiers are preferably used in a total of component (b) and component (c) of 1 to the total composition.
-15 mass%, more preferably 5-10 mass%. When the amount is within this range, the composition can be easily emulsified, and there is no stickiness when applied to the skin, and the stability of the composition is also improved. Also,
The compounding ratio of the component (b) to the component (c) is preferably (b) / (c) = 100: 0 to 50:50, more preferably 90/10 to 60/40 by mass ratio.

The oily bases used in the present invention include, for example, hydrocarbons such as squalane, liquid paraffin, petrolatum, and microcrystalline wax, and silicone oils such as methylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, and the like. , Waxes such as beeswax,
Higher alcohols such as cetyl alcohol and stearyl alcohol, sterols such as cholesterol, fatty acid esters such as octyl dodecyl oleate, oleyl oleate, cetyl octanoate, isopropyl myristate, myristyl myristate, aluminum stearate, and magnesium stearate And the like metal soaps. These can be used alone or in combination of two or more. The application amount of these oily bases is preferably from 1 to 80% by mass, more preferably from 10 to 70% by mass, based on the whole composition. It is preferable that the amount of the oily base used is within this range, because the emulsification can be easily performed and the feeling of use is good. The mixing ratio of the water phase and the oil phase of the emulsified skin external preparation composition of the present invention is preferably a mass ratio of water phase / oil phase = 50/50 to 90/10, more preferably 60/40 to 80 /. 20. It is preferable that the mixing ratio be within this range since the feeling in use is good.

The composition of the present invention contains, in addition to the above essential components, a humectant, an anti-inflammatory agent other than those described above, vitamins, a thickener, an antioxidant, a chelating agent, a preservative, a refreshing agent,
Various additives such as conditioning agents and fragrances can be further used. Specifically, examples of the humectant include polyhydric alcohols such as urea, glycerin, sorbitol, 1,3-butylene glycol, polyglycerin, and polyethylene glycol; amino acids; and natural moisturizing components (NMF) such as sodium pyrrolidonecarboxylate. , Collagen, hyaluronic acid, heparin-like substances, water-soluble polymers such as mucopolysaccharides such as chondroitin sulfate, and the like. Examples of the vitamins include oil-soluble vitamins such as tocopherol, tocopherol acetate, retinol palmitate, and vitamin A oil, and water-soluble vitamins such as pyridoxine hydrochloride. Examples of the thickener include natural polymers such as sodium alginate, xanthan gum, tragacanth gum, starch, semi-synthetic polymers such as sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, dextrin palmitate, and synthetic polymers such as carboxyvinyl polymer and polyvinyl alcohol. And the like. Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, and ascorbic acid. Examples of the chelating agent include disodium edetate, ethylenediaminetetraacetate, pyrophosphate, hexametaphosphate, and gluconate. can do. Examples of preservatives include parabens, benzoates, benzalkonium chloride and the like. 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, potassium hydrogen phosphate, and the like. The compounding amount of each optional component is preferably 0.01 to 30% by mass, more preferably 0.1 to 20% by mass of the whole composition of the present invention. Emulsions targeted by the present invention include external medicines, quasi-drugs, and general skin cosmetics, and the dosage form can be arbitrarily selected according to the purpose, and is in the form of a cream, an ointment. , Emulsion, pack, stick, etc. The skin external preparation which is the water-in-oil emulsion of the present invention can be prepared by a conventional method.

[0007]

The present invention will be described below in detail with reference to examples and comparative examples. Among the components shown in Tables 1 to 10, an oil component and an aqueous component were mixed and heated and dissolved at 70 ° C. An aqueous component was added to the oil component, and the mixture was emulsified by an emulsifier to prepare a W / O emulsified skin external preparation according to the present invention. After the preparation, the emulsified type was judged by the electric conductivity. The emulsion particle size was measured with a microscope. In addition, it was stored at 25 ° C. and 40 ° C. for one month, and the stability was examined by the state of phase separation and the change in particle size. The state of phase separation was evaluated on the following four levels, and △ ○ △ was judged to be a stable level. The results are shown in Tables 1 to 10. (Phase separation state: no change ◎, slight decrease in viscosity ○, viscosity decrease △, oil seepage and phase separation ×) Storage stability was comprehensively evaluated based on the phase separation state and the change in particle size. Was judged to be a stable level. (Criterion: no change ◎; slight decrease in viscosity, little change in particle size ○: decrease in viscosity, increase in particle size Δ; exudation of oil, phase separation ×)

[0008]

[Table 1]

[0009]

[Table 2]

[0010]

[Table 3]

[0011]

[Table 4]

[0012]

[Table 5]

[0013]

[Table 6]

[0014]

[Table 7]

[0015]

[Table 8]

[0016]

[Table 9]

[0017]

[Table 10]

Of the lipophilic emulsifiers of component (b) in the table,
Decaglyceryl pentaoleate is converted to tetraglyceryl tristearate, hexaglyceryl tristearate,
Example 1 when changing to hexaglyceryl pentaoleate, decaglyceryl tristearate, decaglyceryl trioleate, and decaglyceryl pentastearate
Storage stability equivalent to that of was observed. When sorbitan tristearate was changed to trioleic acid, the same stability as in Example 2 was observed. POE (10) The POE chain length of trimethylolpropane tristearate is 3, 5, 8
In all cases, storage stability equivalent to that of Example 4 was observed. In addition, POE (10) trimethylolpropane tristearate is replaced by POE (3) trimethylolpropane triisostearate, POE (3) trimethylolpropane trimyristate, POE (5) trimethylolpropane trimyristate, POE (8) When changing to trimethylolpropane trimyristate,
Storage stability equivalent to that of Example 4 was observed. POE (1
0) Castor oil, POE (10) When the POE chain length of the hydrogenated castor oil was changed to 3, 5, or 7, storage stability equivalent to that of Example 5 or Example 6 was observed. When the EO chain length of POE (10) triisostearate-hardened castor oil was changed to 5, 15, 20, 30 and the castor oil of POE (10) -triisostearate was lauric acid P
OE (20) hydrogenated castor oil, isostearic acid POE
(5) Hardened castor oil, POE isostearate (10)
Hardened castor oil, POE (15) hardened castor oil and POE (20) hardened castor oil were replaced with hardened castor oil, and storage stability equivalent to that of Example 7 was observed.

Example 63 Hand Rough Cream Table 11 (g / 100g) The aqueous phase component and the oil component were mixed and heated and dissolved at 70 ° C. The aqueous phase component was added to this oil phase component and emulsified by an emulsifier. The emulsion type of the obtained cream was determined to be W / O type based on the electric conductivity. When the particle size of the emulsified particles was measured with a microscope, it was about 1 μm. Further, when the storage stability was observed, there was no change in appearance at both 25 ° C. and 40 ° C., and the particle size after storage was about 1 μm, indicating excellent stability.

Example 64 Moisturizing Emulsion Table 12 (g / 100g) The aqueous phase component and the oil component were mixed and heated and dissolved at 70 ° C. The aqueous phase component was added to this oil phase component and emulsified by an emulsifier. The emulsion type of the obtained emulsion is W
It was determined to be a / O type. When the particle size of the emulsified particles was measured with a microscope, it was about 1 μm. further,
Observation of storage stability revealed that there was no change in appearance at both 25 ° C. and 40 ° C., and the particle size after storage was about 1 μm.
m, indicating excellent stability.

Example 65 Moisturizing Pack (Wipe Type) Table 13 (g / 100g) The aqueous phase component and the ethanol phase component were mixed and dissolved by stirring. The aqueous phase component was added to the ethanol phase component to solubilize it. The emulsified type of the obtained pack agent was determined to be W / O type based on electric conductivity. When the particle size of the emulsified particles was measured with a microscope, it was about 1 μm. Further, when the storage stability was observed, there was no change in appearance at both 25 ° C. and 40 ° C., and the particle size after storage was about 1 μm, indicating excellent stability.

Example 66 Insect stick stick preparation Table 14 (g / 100g) The aqueous phase component and the oil component were mixed and heated and dissolved at 70 ° C. An aqueous phase component was added to the oil phase component, and the mixture was emulsified by an emulsifier. The emulsified product was poured into a cylindrical mold to form a cooling paper stick. The emulsified type of the obtained stick was determined to be W / O type based on electric conductivity. When the particle size of the emulsified particles was measured with a microscope, it was about 1 μm. Furthermore, when the storage stability was observed, it was found that
There was no change in appearance at either 0 ° C., and the particle size after storage was about 1 μm, indicating excellent stability.

As described above, the skin external preparation composition of the present invention can use a polar oil-soluble drug which has conventionally been difficult to be incorporated into a W / O emulsion, and has a wider temperature range. It has excellent storage stability over a wide range.

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Claims (3)

[Claims] 1. An oil-soluble drug having an IOB value of 0.1 to 2; and (b) a lipophilic emulsifier having at least two hydrophobic groups containing a hydrocarbon chain having 8 or more carbon atoms in a molecule thereof. A water-in-oil type emulsified skin external preparation composition characterized by containing: 2. The water-in-oil type according to claim 1, further comprising (c) a lipophilic emulsifier having one hydrophobic group containing a hydrocarbon chain having 8 or more carbon atoms in the molecule. An emulsified skin external preparation composition. 3. The oil-soluble drug is selected from the group consisting of crotamiton, glycyrrhetinic acid, hydrocortisone, prednisolone, dexamethasone, indomethacin, ketoprofen, suprofen, piroxicam, bufexamac, felbinac, ufenamate, lidocaine, dibucaine, and diphenhydramine. The water-in-oil type emulsified skin external preparation composition according to claim 1 or 2, wherein the composition is two or more types.