JP2001181122A - Slightly water-soluble aromatic compound-containing composition for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical preparation for external use that can stably include active ingredients slightly soluble in water. SOLUTION: The objective pharmaceutical preparation for external use characteristically includes the component (1): a water-soluble polymeric compound bearing a quaternary cationic group, and the component (2): a slightly water-soluble aromatic compound bearing an amine oxide group.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an external preparation composition which can be suitably used for hair, skin, dandruff and the like.

[0002]

2. Description of the Related Art Conventionally, many active ingredients that are blended in order to impart functions to products have poor water solubility.
It has been difficult to stably mix it in aqueous products such as detergents. For example, bis- [1-hydroxy-2 (1H) -pyridinethionate] zinc (hereinafter, zinc pyrithione) or 1-hydroxy-4-methyl-6- (2,4,4-trimethyl) which is generally used as an anti-dandruff agent (Pentyl) -2 (1H) -pyridonemonoethanolamine (hereinafter, pyroctonolamine), 6-cyclohexyl-1-hydroxy-4-methyl-2 (1H) -pyridonemonoethanolamine (hereinafter, cyclopyroxolamine) ) And other active ingredients are widely known as anti-dandruff agents for shampoos,
Although these active ingredients are used, they dissolve under alkaline conditions of pH 9 or higher, but hardly dissolve in water in the neutral region (pH 6 to 9), which is a normal detergent pH, so that the body (hair, scalp) And the like) as an active ingredient in the composition of the present invention. Therefore, in ordinary detergent compositions, for example, by adding a thickening polymer, by increasing the viscosity of the whole system, to suppress the sedimentation of these poorly water-soluble substances, such as a method of stably compounding Has been taken.

For example, Japanese Patent Application Laid-Open No. Hei 4-243812 discloses that an anionic polymer such as an acrylic acid polymer is used to suspend mica coated with titanium dioxide as an active ingredient. Also, JP-A-51-73138
The publication discloses that an amphoteric polymer is used to make a water-soluble cerium salt as an active ingredient or a poorly water-soluble substance obtained from the salt thereof and a polymer substance water-soluble. Also,
JP-A-61-151110 discloses that zinc pyrithione as an active ingredient is dispersed and stabilized using a nonionic polymer such as hydroxypropylhydroxyethylcellulose. In addition,
8-396111, JP-A-58-180417, JP-A-58-183614 and JP-A-2-183.
Japanese Patent Application Publication No. 11713 discloses a method of stably blending the above-mentioned active ingredient by thickening the system using a compound other than a polymer. In addition, Tokio Table 1
Japanese Patent Application Laid-Open No. 0-512568 discloses that a fine particle dandruff inhibitor (sulfur, selenium sulfide, pyridinethione salt) as an active ingredient is finely dispersed using a cationic polymer. No. 18713 discloses that zinc pyrithione as an active ingredient is suspended using glucan gum, guar gum, hydroxyethyl cellulose, and a cationic polymer. However, even if these polymers are used,
The active ingredient is only temporarily dispersed and has not yet been solubilized. When a thickener is used,
Inappropriate viscosity increase in the product is inevitable.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide an external preparation composition containing a poorly water-soluble active ingredient stably.

[0005]

Means for Solving the Problems The present inventors have made intensive studies to solve the above problems, and as a result, when a specific polymer having a quaternary cation group in the molecule is used in combination, a poorly water-soluble active ingredient is obtained. It was possible to stably solubilize, thereby solving the above problem. That is, the present invention provides an external preparation composition comprising: (1) a water-soluble polymer compound having a quaternary cation group; and (2) a poorly water-soluble aromatic compound having an amine oxide group. provide.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The water-soluble polymer having a quaternary cation group as the component (1) used in the present invention is a water-soluble polymer having a quaternary cation group in the molecule. Here, it is preferable that the water-soluble polymer is such that an aqueous solution obtained when 10 g of a polymer is charged and stirred in 100 g of ion-exchanged water is uniformly transparent. The cationic group in the polymer is not particularly limited, but is preferably a quaternary ammonium group. Examples of the cationic water-soluble polymer of the component (1) include a water-soluble polymer having a hydroxyl group such as a natural polymer such as pullulan, dextran, starch, guar gum or polyvinyl alcohol, and a cationizing agent such as glycidyl trialkyl ammonium halide. (Eg, glycidyltrimethylammonium chloride). Particularly preferred cationic water-soluble polymers are cationized pullulan and cationized dextran.

Further, as the cationic water-soluble polymer of the component (1), a synthetic polymer obtained by copolymerizing a cationic monomer and a nonionic water-soluble monomer can be used.
A hydrophobic monomer may be further copolymerized as long as the water solubility of the polymer is not lost. The cationic monomer is not particularly limited as long as it contains a quaternary cationic group in the final polymer. Examples of the monomer include (meth) acryloylalkyltrialkylammonium halide and dialkyldiallylammonium halide. When a dialkylaminoalkyl (meth) acrylate is used, an alkyl halide (C _n H _{2n + 1} X; n = 1 to 18, X = Br, Cl,
Quaternization with I) or dialkyl sulfate is preferred. Here, the alkyl group in the monomer is preferably one having 1 to 4 carbon atoms. Specific examples of dialkylaminoalkyl (meth) acrylate include dimethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate, dimethylaminobutyl (meth) acrylate, diethylaminoethyl (meth) acrylate, and diethylaminopropyl (meth) acrylate , Diethylaminobutyl (meth) acrylate, dipropylaminoethyl (meth) acrylate, dipropylaminopropyl (meth) acrylate, dipropylaminobutyl (meth) acrylate, and the like, more preferably, dimethylaminoethyl (meth) acrylate, Dimethylaminopropyl (meth) acrylate, diethylaminoethyl (meth) acrylate and the like. For the quaternization, C ₁ -C ₁₈ alkyl halides can be used, but dimethyl sulfate, diethyl sulfate, dipropyl sulfate and the like may be used. It is preferable to use ethyl bromide, methyl chloride, hexyl bromide, octadecyl bromide, dimethyl sulfate, diethyl sulfate and the like. The quaternization ratio is desirably 50% by mass (hereinafter abbreviated as%) or more. If the quaternization ratio is within this range, a tertiary amino group may remain.

Examples of (meth) acryloylalkyltrialkylammonium halides include (meth)
Acryloylethyltrimethylammonium, (meth)
Acryloylpropyltritrimethylammonium,
(Meth) acryloylbutyltrimethylammonium,
(Meth) acryloylethyltriethylammonium,
Examples include halides such as (meth) acryloylpropyltriethylammonium and (meth) acryloylbutyltriethylammonium, and among these, halides such as (meth) acryloylethyltrimethylammonium and (meth) acryloylpropyltrimethylammonium are particularly preferable. These halides are not particularly limited, but are preferably chloride and bromide. Further, as the cationic monomer, dialkyldiallylammonium halide, more specifically, dimethyldiallylammonium halide, diethyldiallylammonium halide, dipropyldiallylammonium halide, dibutyldiallylammonium halide, and the like can be used. Is preferred. The halide of the monomer used here is not particularly limited, but is preferably chloride or bromide.

The nonionic monomer to be copolymerized is not particularly limited as long as it has copolymerizability with a cationic monomer and the obtained polymer exhibits cationicity and water solubility. Examples of the nonionic water-soluble monomer include (meth) acrylamide, hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, and alkoxypolyoxyethylene glycol (meth) acrylate. The terminal of the ethylene oxide adduct may include a terminal blocked with a hydroxyl group, an alkoxy group, or a phenoxy group. For example, it is preferable to use methoxypolyethylene glycol (meth) acrylate. Further, the molecular weight of the polyoxyethylene portion may be independent or may have a distribution, and the number of added moles m of the oxyethylene portion is 1 to 1 in terms of an average value or a single number.
A range of 50 is preferred. Furthermore, these alkoxypolyethylene glycol (meth) acrylates are used by mixing two or more kinds of alkoxypolyoxyethylene glycol (meth) acrylates having different m as long as the mole number m of the oxyethylene portion is in the range of 1 to 50. May be.

The hydrophobic monomer that can be copolymerized is not particularly limited as long as it is a monomer that can be copolymerized with a cationic monomer or a nonionic water-soluble monomer, and specific examples thereof include alkyl (meth) acrylates. , Alkyl (meth) acrylamide and the like,
Preferably an alkyl (meth) acrylate, more preferably an alkyl (meth) having an alkyl chain length of 1 to 10.
Acrylic ester. The water-soluble polymer compound of the component (1) of the present invention has an average molecular weight of 1,000 to 10,000.
It is preferably 0000, more preferably 5,0
00 to 1,000,000, more preferably 10,000.
00 to 500,000. The use of a compound having a molecular weight in this range is preferable because good product viscosity and active ingredient stability can be exhibited. The content of the component (1) in the composition may vary depending on the content of the component (2). For example, the content is preferably 0.01 to 5.0% based on the mass of the composition. Preferably, it is more preferably 0.05 to 2.0%.

The water-soluble polymer compound of the component (1) can be obtained, for example, by various known polymerization methods, but is preferably carried out by solution polymerization or emulsion polymerization. As the polymerization solvent, a lower or higher alcohol such as methanol, ethanol, or 2-propanol, or a lower ketone such as acetone alone or a mixed solvent, or a mixed solvent of these and water is preferably used. When a mixed solvent containing water is used, the amount of water in the solvent is preferably from 10 to 50%, more preferably from 20 to 35%. As the polymerization initiator,
There is no particular limitation as long as it is soluble in the solvent used,
For example, 2,2′-azobisisobutyronitrile,
2'-azobis (2-methylbutyronitrile), 2,
2′-azobis (2,4-dimethylvaleronitrile),
2,2′-azobis (2-amidinopropane) dihydrochloride, 2,2′-azobis (N, N′-dimethyleneisobutylamidine), potassium persulfate, ammonium persulfate, aqueous hydrogen peroxide, and the like, The use amount is preferably set to 0.02 to 5% based on the monomer. The polymerization temperature varies depending on the polymerization solvent used.
The temperature is preferably 90 ° C, more preferably 75 to 90 ° C.
° C. The polymerization time is preferably 3 to 8 hours, more preferably 4 to 6 hours.

The poorly water-soluble aromatic compound having an amine oxide group of the component (2) includes zinc pyrithione, pyrocton olamine and ciclopirox olamine. Of these, pyroctone olamine is preferred.
In the present invention, the content ratio of the component (2) in the composition varies depending on the function imparted to the composition. For example, the content is preferably 0.05 to 2% based on the mass of the composition. Preferably, it is more preferably 0.1 to 1%. By setting the concentration in this range, the stability of the component (2) in the composition can be particularly improved. In the present invention, when the components (1) and (2) are put into water, the component (1) acts as a solubilizing agent for the component (2). That is, component (1)
Forms a complex in a state in which the component (2) is incorporated. Specifically, the average particle system of the component (2) poorly water-soluble aromatic high molecular compound is set to 200 nm or less by a dynamic light scattering method. it can.

In the present invention, the above component (1)
It is preferable to mix both components such that the mass ratio of / (2) is 1/9 to 7/3, and more preferably 2/8 to 6
/ 4, and more preferably 3/7 to 5/5. Also,
The composition of the present invention may be an aqueous composition. At this time, the pH is preferably set to 6.0 to 9.0. Furthermore, the product can be blended with various surfactants. At this time, the surfactant that can be used is not particularly limited. Also, a mixture of various surfactants may be used. The surfactant used in the aqueous system may be any of conventionally used anionic surfactants, nonionic surfactants, amphoteric surfactants, and cationic surfactants, for example, α-sulfo surfactants. Fatty acid methyl ester salts (especially alkali metal salts such as sodium or potassium salts), α-olefin sulfonates (especially alkali metal salts such as sodium or potassium salts), fatty acid soaps (alkali of fatty acids having 10 to 18 carbon atoms) Metal salt), polyoxyethylene alkyl ether sulfate and the like. Examples of nonionic surfactants include polyoxyethylene alkyl phenyl ethers such as polyoxyethylene nonyl phenyl ether, polyoxyethylene alkyl ether, polyoxyethylene fatty acid esters, and polyoxyethylene polyhydric alcohol fatty acid partial esters. be able to. Examples of amphoteric surfactants include:
Betaines such as N, N-dimethyl-N-dodecyl-N-carboxymethylammonium betaine; Examples of the cationic surfactant include cetyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearylbenzylammonium chloride, eicosyltrimethylammonium chloride, distearylpolyethenoxyethylammonium ethyl sulfate, and dipalmitylpolyethenoxyethylammonium halide. And cationic surfactants such as Nα-palmitoyl-L-arginine ethyl ester / DL-pyrrolidone carboxylate.

When used in combination with an anionic surfactant, it is preferable that the components (1) and (2) of the present invention are sufficiently mixed and solubilized before mixing with the anionic surfactant. In addition, within the range that does not impair the effects of the present invention, for normal hair, various active ingredients to be added to the composition for skin, chelating agents, hydrotropes, pH adjusters, viscosity adjusters, antioxidants, antiseptics, UV inhibitors, emulsions, pearls,
Flavors and pigments can also be included. The external preparation composition of the present invention can be mixed with various liquid products, or may be a sheet-like product obtained by impregnating a nonwoven sheet with a solution, or may be further combined with a polymer absorbent and a gelling agent to form a gel. Formulations are also possible. Alternatively, the liquid composition may be filled in a spray container or a container having a foaming mechanism, and used in the form of a mist, mist, or foam. The present invention, in particular, zinc pyrithione, pirocton olamine, shampoo for dandruff containing as an active ingredient ciclopirox olamine, rinse-in shampoo, rinse,
Conditioner, treatment, hair styling, hair restorer,
It can be effectively applied to hair, scalp and skin products such as hair setting agents, lotions, emulsions and remedies for acne.

[0015]

According to the present invention, a poorly water-soluble aromatic compound having an amine oxide group is solubilized, for example, even in an aqueous product in the pH range (6 to 9), which has been considered difficult in the past. For example, it is possible to provide a product in which the component (2) is stably compounded in an aqueous product.

[0016]

EXAMPLES Example 1 The following polymers 1 to 4 were prepared as component (1) compounds,
Their ability to solubilize the compound of component (2), zinc pyrithione, pyrocton olamine and ciclopirox olamine was compared to polymers 5-7 as comparative examples. The above-mentioned Polymers 1 to 4 and Comparative Polymers 1 to 3 were produced by the following synthesis.

Cationic polymer 1 In a 1-liter four-neck separable flask equipped with a stirrer, a reflux condenser and a nitrogen inlet tube, 50 g of dimethylaminoethyl methacrylate, 50 g of ethyl methacrylate,
After 200 g of ethanol was added and uniformly dissolved, nitrogen gas was introduced from a nitrogen introduction tube with stirring. 20 minutes later,
2,2'-azobis (2-methyl-butyronitrile)
An initiator solution obtained by dissolving 0.5 g in ethanol 100 g was added, and the mixture was heated in an oil bath at 90 ° C. to start a polymerization reaction.
Polymerization was performed at 90 ° C. for 6 hours while introducing nitrogen to obtain a prepolymer. 20 g of ethyl bromide was added to 100 g of an ethanol solution of the prepolymer (solid content of 26.4 wt% by a ket moisture meter), and the mixture was stirred at 50 ° C. overnight.
The solvent was removed from the content, and the unreacted monomer and odorous residue were removed with a vacuum dryer to obtain the intended cationic polymer 1. (Average molecular weight 60,000)

Cationic Polymer 2 In a 1-liter four-neck separable flask equipped with a stirrer, a reflux condenser and a nitrogen inlet tube, 45 g of methoxypolyethylene glycol methacrylate (n = 9) and 55 g of trimethylammonium methacrylate chloride were added.
After 200 g of ethanol was added and uniformly dissolved, nitrogen gas was introduced from a nitrogen introduction tube with stirring. 20 minutes later,
2,2'-azobis (2-methyl-butyronitrile)
An initiator solution obtained by dissolving 0.3 g in 100 g of ethanol was added, and the mixture was heated in an oil bath at 90 ° C. to start a polymerization reaction. After polymerizing at 90 ° C. for 6 hours while introducing nitrogen,
The solvent was removed from the content, and the unreacted monomer and odorous residue were removed with a vacuum dryer to obtain the intended cationic polymer 2. (Average molecular weight 100,000)

Polymer 3: (Cationized natural polymer) A cationizing agent (glycidyltrimethylammonium chloride) was added to a commercially available aqueous solution of pullulan, and the mixture was stirred under heating to obtain a cationized pullulan.

Polymer 4: (Cationized natural polymer) A cationizing agent (glycidyltrimethylammonium chloride) was added to a commercially available aqueous dextran solution, and the mixture was stirred under heating to obtain a cationized dextran.

Comparative polymer 5: Dextran without cationization Comparative polymer 6: Pullulan without cationization Comparative polymer 7: The same procedure as for Polymer 2 was used except that only 100 g of methoxypolyethylene glycol methacrylate (n = 9) was used. Comparative polymer 7 was obtained.

Evaluation of Stability of Active Ingredient (2) in Aqueous Composition 0.5% of any of Polymers 1 to 7 described above and an active ingredient (zinc pyrithione, pyrocton olamine or ciclopirox olamine) 3%, the balance being water, the degree of stability of the active ingredient (2) immediately after production in a composition in which the pH has been adjusted with a pH adjuster (citric acid and sodium hydroxide) as shown in Table 1 below, And the degree of stability of the active ingredient (2) after storage at 25 ° C. for 8 weeks was evaluated. The evaluation of the degree of stability was made by the dynamic light scattering method (DL
When the value of the average particle diameter measured in S) was 100 nm or less, the result was rated as ◎, when the value was higher than 100 nm and 200 nm or less, the result was ○, and when the value was 200 nm or more, the result was ×. The results are shown in Table 1.

Table 1 After storage: The average particle system after storage at 25 ° C. for 8 weeks was measured and evaluated.

Evaluation of stability of active ingredient (2) in product Using the above cationic polymer and ingredient (2), according to a known production method, dandruff shampoo (Table 2), rinse (Table 3), hair growth Agent (Table 4), body soap (Table 5),
When an acne treatment agent (Table 6) was manufactured and the polymer was blended at the content shown in each table, the component (2) could be stably blended in any of these products, and it was found that the long-term treatment was effective. Stable over time. Here, the pyrocton olamine-cationic polymer composite is prepared by mixing pyrocton olamine / cationic polymer 1 at a ratio of 3/5.

Table 2: Dandruff shampoo

Table 3: Rinsing * 1: XM-503LN manufactured by Lion Chemical or Leogard GP or polymer manufactured by UCC-JR400 * 2: Yuka Former AM75201 manufactured by Mitsubishi Yuka

Table 4: Hair restorer

Table 5: Body soap * 1: Shin-Etsu Chemical Co., Ltd. Metroose 65SH-1
500 * 2: XM-503LN or LEOGARD GP manufactured by Lion Chemical or Polymer-JR400 manufactured by UCC

Table 6: Acne treatments

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (Reference) A61K 7/075 A61K 7/075 7/08 7/08 7/48 7/48 7/50 7/50 C08K 5/3432 C08K 5/3432 5/41 5/41 C08L 3/00 C08L 3/00 3/02 3/02 101/14 101/14 (72) Inventor Miyuki Miyake 1-3-7 Honjo, Sumida-ku, Tokyo Rio (72) Inventor Yoshifumi Yamagata 1-3-7, Honjo, Sumida-ku, Tokyo F-term in Lion Corporation (reference) 4C083 AA082 AA112 AB032 AB112 AB432 AB442 AC022 AC072 AC102 AC122 AC212 AC242 AC302 AC352 AC392 AC402 AC422 AC432 AC442 AC472 AC532 AC542 AC552 AC562 AC612 AC662 AC692 AC782 AC851 AC852 AC931 AD021 AD022 AD092 AD131 AD132 AD211 AD282 AD662 CC02 CC23 CC37 CC38 CC39 DD23 DD27 DD31 EE11 EE14 EE21 EE22 EE23 4J002 AB051 BG071 GB131

Claims (6)

[Claims] 1. An external preparation composition comprising component (1) a water-soluble polymer compound having a quaternary cation group and component (2) a poorly water-soluble aromatic compound having an amine oxide group. 2. The poorly water-soluble aromatic compound having an amine oxide group of the component (2) is at least one member selected from the group consisting of zinc pyrithione, pyrocton olamine and ciclopirox olamine. 2. The external preparation composition according to item 1. 3. The water-soluble polymer compound of the component (1),
The external preparation composition according to claim 1 or 2, which is a cationized natural polysaccharide that is cationized pullulan or cationized dextran, or a copolymer of a cationic monomer and a nonionic water-soluble monomer. 4. The mass ratio of component (1) / component (2) is 1 /
The external preparation composition according to any one of claims 1 to 3, wherein the composition is 9 to 7/3. 5. The method according to claim 1, which is used for hair and skin.
An external preparation composition according to any one of the above. 6. The method according to claim 1, which is used for preventing aqueous dandruff.
An external preparation composition according to any one of the above.