JPH09110702A - Gel preparation containing seawater in deep ocean - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a gel preparation containing seawater in deep ocean which is prepared by making seawater in deep ocean into gel with a specific gelling agent, shows excellent transdermal absorption of seawater in deep ocean which is effective in treatment for skin diseases, in addition, can formulate the seawater in high concentration, as it maintains high adhesion to skin and good application feeling. SOLUTION: (A) Seawater in the deep layer of the ocean (preferably in the depth of >=100m) is converted to a gel form with a cross-linked product of a polymer prepared from a monomer of the formula: CH2 =CH-NR<1> -COR<2> (R<1> and R<2> are each H, methyl) or another cross-linked product of copolymer prepared from the monomer and another monomer copolymerizable therewith where the amount of the seawater (A) is preferably 1-90 pts.wt., while the cross- linked product (B) is 5-20 pts.wt. This preparation is obtained by mixing an aqueous solution and/or a solvent solution of the polymer with the seawater. The cross-linked polymer (component B) is prepared by carrying out the (co) polymerization in the presence of a cross-linking agent such as divinylbenzene or the like in an aqueous medium using a water-soluble azo compound as a polymerization initiator in a nitrogen gas atmosphere at 10-70 deg.C.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention provides a deep-sea-water-containing gel preparation prepared by formulating deep-sea water using a gelling agent. The gel preparation containing deep sea water of the present invention is applied to skin diseases such as atopic dermatitis.

[0002]

2. Description of the Related Art As a method for treating skin diseases such as atopic dermatitis, topical therapy has been carried out by applying medicinal components such as various steroids to the affected area in the form of ointments, creams, liquids and aerosols. However, steroids and the like can only be treated as a first-line coping therapy, and when the frequency of use increases, side effects strongly appear. Therefore, it is necessary to pay attention to the use and it is difficult to use for a long period of time. On the other hand, many of those with less side effects have less effect on itching. In addition, especially in the case of atopic dermatitis, it is said that the hot spring therapy is effective, but it is inferior in terms of convenience and does not last long. Further, as the dosage form, the liquid formulation and the aerosol formulation were small in the amount applied to the affected area and were inferior in sustainability. Therefore, an effective and long-lasting external treatment is expected, and as the dosage form, a gel preparation and a highly safe external preparation are desired for the above reasons.

On the other hand, in recent years, a skin treatment method for atopic skin diseases and the like using "deep sea water" in the sea at a depth of 100 meters or more has been considered effective. (Eg 19
(Kochi Shimbun, June 1, 1994) Deep water is rich in nitrate nitrogen, phosphate phosphorus, and silicate silicon, which are about 20 times, 10 times, and 12 times higher than surface seawater, respectively. On the other hand, nitrite-type nitrogen and ammonia-state nitrogen have low concentrations in both deep-water and surface water. This characteristic is consistent at all sampling points of deep water. Furthermore, since deep water is not exposed to sunlight, it is considered to be clean seawater with few bacteria and plankton, and the development of an external preparation using this is an urgent task. On the other hand, as a base for an external preparation, a hydrogel base containing a water-soluble polymer such as polyacrylic acid, starch, tragacanth, alginic acid or a cellulose derivative has been conventionally used. However, since polymers made from acrylic acid and its salts are anionic, deep water,
Salts such as sodium chloride present on the skin surface or secreted in sweat are drastically reduced in viscosity to become liquefied or dull, which makes formulation difficult.
Furthermore, even in the case of a formulation that can be prepared, there is a problem in that the skin absorbability is lost after application to the skin, the skin absorbency is lost, the usability is deteriorated, and clothes are soiled. Further, there are problems that a complex is formed with other components in the deep water to lower the absorbability and destabilize the deep water. Furthermore, the alkali metal salt of polycarboxylic acid has poor affinity with alcohols such as ethanol and isopropanol, and when blending alcohols, it is necessary to neutralize them with an organic amine such as diisopropanolamine. It required skill to make the rheological properties of the gel uniform, and the process had to be complicated. In addition, although these polymers have low skin irritation, the problem of toxicity of the residual monomer still remains. When applied to the skin or the like, the skin irritation of the residual monomer occurs even if the adhesion to the skin is good. It was a fatal defect especially in patients with sensitive atopic dermatitis of the skin. Further, in order to obtain a high gel strength, it was necessary to use a high concentration. In addition, natural polymers are unstable in price, easily exposed to microorganisms, and have the problem of decay. There is no point in using clean deep water. And was causing discomfort to the animal's body.

[0004]

DISCLOSURE OF THE INVENTION The object of the present invention is to improve the above-mentioned problems of the prior art, and to bring about an effect for the treatment of skin diseases due to the efficient transdermal absorbability of deep water, and to achieve a high concentration of deep water. It is intended to provide a deep-water-containing gel agent which can be blended in, has excellent adhesion, and has a good feeling in use.

[0005]

Means for Solving the Problems As a result of earnest studies on a gel preparation which can contain an inorganic salt in a high concentration, the present inventors have found that a polymer or copolymerizable monomer of N-vinylacetamide is used. It was found that the above object can be achieved by using a crosslinked product of a copolymer obtained by copolymerization (hereinafter, also referred to as "crosslinked (co) polymer"), and the present invention has been completed. Hereinafter, the present invention will be described in more detail.

The present invention relates to a homo-crosslinked polymer of N-vinylacetamide gel preparation capable of containing a high concentration of an inorganic salt or a repeating unit represented by the following general formula [2].
A cross-linking copolymer composed of one or more repeating units is an essential component. The present invention is represented by (A) the following general formula (1) CH ₂ ═CH—NR ¹ —COR ² (1) (wherein R ¹ and R ² independently represent a hydrogen atom or a methyl group). Deep seawater characterized by being formed by gelling by including a crosslinked product of a polymer having a compound as a monomer or a crosslinked product of a copolymer of the compound with a copolymerizable monomer and deep sea water Water-containing gel formulation.

(B) The compound represented by the general formula (1) is N
- a vinyl acetamide, in copolymerizable monomer represented by the following general formula _{(2) CH 2 = CR-} COOM (2) ( wherein, R represents a hydrogen atom or a methyl group, M represents a hydrogen atom or an alkali metal The deep-sea-water-containing gel preparation according to claim 1, which is a compound represented by the atom.

The deep sea water-containing gel preparation according to claim 1, wherein the crosslinked product of the polymer (C) or the crosslinked product of the copolymer is in the form of fine particles having an average particle size of 10 μm or less. (D) The crosslinked product of the polymer or the crosslinked product of the copolymer is 5 to 2
The deep sea water-containing gel preparation according to claim 1, wherein 0 part by weight and 1 to 90 parts by weight of deep sea water are contained. The deep sea water-containing gel preparation according to claim 1, wherein the formulation (E) is a cream.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION General formula (1) used in the present invention
Examples of the compound N-vinylcarboxylic acid amide represented by: include N-vinylformamide, N-methyl-N-vinylformamide, N-vinylacetamide, and the like. In particular, N-vinylacetamide can be preferably used. . As the monomer copolymerizable with the compound represented by the general formula (1), for example, the compound represented by the general formula (2) can be preferably used. Examples of the compound represented by the general formula (2) include acrylic acid, sodium acrylate, potassium acrylate, methacrylic acid and sodium methacrylate.

In a crosslinked (co) polymer having N-vinylacetamide and the compound represented by the general formula (2) as a monomer, the compound represented by the general formula (2) is 50% of all monomers.
If it exceeds 5% by weight, the anionicity becomes high, which lowers the physical properties of the gel due to salt and the release of the active ingredient from deep sea water, which is not preferable.

Further, in the present invention, a crosslinking agent is added during the polymerization of the above-mentioned monomer and copolymer for the purpose of increasing the gel strength, imparting the structural viscosity, and reducing the stickiness to the skin. The cross-linking agent is not particularly limited, but for example, N, N-1,4-butylene bis (N-vinyl acetamide), N, N-1,6-hexylene bis (N-vinyl acetamide), N, N -Decylene bis (N-vinyl acetamide), N, N-3-oxa-1,5-pentylene bis (N-vinyl acetamide), N, N-3,6
-Dioxaoctylene bis (N-vinyl acetamide), N, NP-xylene bis (N-vinyl acetamide), N, N'-diacetyl-N, N'-divinyl-
1,4-bisaminomethylcyclohexane, tetraallyloxyethane, triallyl phosphate, trimethylolpropane diallyl ether, sucrose allyl ether, N, N′-methylenebisacrylamide, ethylene glycol di (meth) acrylate, diethylene glycol di ( Unsaturated in one molecule such as (meth) acrylate, triethylene glycol di (meth) acrylate, polyethylene glycol di (meth) acrylate, trimethylolpropane tri (meth) acrylate, pentaerythritol triallyl ether, divinylbenzene, divinyl ether. The compound which has two or more groups is mentioned.

The case where N-vinylacetamide is used as the compound represented by the general formula (1) will be described below as an example. The cross-linking agent is N-vinyl acetamide and [2]
With respect to the total amount of the monomers represented by
It is used in the range of 1 / 2,000, preferably 1/20 to 1/500. If the amount of the cross-linking agent used is less than this range, the effect due to cross-linking cannot be obtained, and the spinnability of the gel is produced, resulting in a marked deterioration of the feeling of use. On the other hand, if it exceeds this range, the crosslink density becomes too high and the adhesion to the skin at the time of application becomes poor, which is not preferable.

Since the crosslinked (co) polymer of the present invention is nonionic to weakly anionic, when the gel preparation of the present invention is applied and applied to the anionic surface of the skin having weak acidity, it is ionic. It is considered that the skin adhesion is higher than that of the above, and the cohesive force can be maintained without the polymer chains expanding and contracting due to the interaction of ions even in the presence of water and salt, so that the physical properties of cream strength can be suppressed. , It is possible to prevent the base material from collapsing and falling off.

Moreover, since the cross-linked (co) polymer of the present invention is hydrophilic, it absorbs water secreted on the skin surface, so that the skin adhesiveness of the gel preparation is maintained and a satisfactory pharmacological effect is obtained. In addition, an equilibrium state is established between the water vapor and the external environment to prevent skin peeling and rash. Further, the crosslinked (co) polymer of the present invention has low toxicity such as skin irritation and skin sensitization.

Since the gel preparation of the present invention is also alcoholic, alcohols such as ethanol and isopropyl alcohol can be added. Ethanol and isopropyl alcohol have a bactericidal and disinfecting action on the skin surface, and if these can be added, the effect of preventing skin irritation due to bacterial growth is expected.

The alcohols used in the present invention include:
Lower monohydric alcohols such as ethanol and propanol, propylene glycol, 1,3-butanediol, ethylene glycol monobutyl ether, triethylene glycol, (dihydric alcohol), glycerin (trihydric alcohol) pentaerythritol (tetrahydric alcohol), Examples include polyhydric alcohols such as xylit (pentahydric alcohol) sorbit (hexahydric alcohol). Polyhydric alcohols are expected to enhance the transdermal absorbability of deep water by increasing the moisturizing properties of the skin. In particular, propylene glycol has an antiseptic action, and glycerin and 1,3-butanediol have an action of relieving the skin irritation of ethanol. Further, since they are soluble in aromatic alcohols such as benzyl alcohol and cyclohexanol, these can also be used.

In addition to alcohol, water or a solvent can be added. Examples of the solvent include organic solvents such as N-methylpyrrolidone which are miscible with water, and organic solvents which are immiscible with water, such as crotamiton.

Further, other polymers may be added to the base, and those which are sufficiently compatible with the copolymer or are compatible with the white turbidity are preferable. For example, these polymers include silicone rubber, acrylic rubber, guar gum, locust bean gum, rubber-based thickening substances such as natural rubber, polyvinyl alkyl ether,
Polyvinyl alcohol, polyvinyl acetate, methyl vinyl ether / maleic anhydride copolymerization, polyvinyl pyrrolidone, carboxyl vinyl polymer, vinyl pyrrolidone /
Vinyl-based thickening substances such as vinyl acetate alkylaminoacrylic acid copolymer, metacarboxybetaine metacarboxyester copolymer, styrene-maleic acid copolymer, ethylene-vinyl acetate copolymer, vinyl acetate-polyvinyl alcohol copolymer , Cellulose thickening substances such as starch, pullulan, ethyl cellulose, cellulose acetate, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxymethyl ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl cellulose phthalate methyl cellulose, carboxymethyl cellulose, (meth) acrylic acid alkyl ester as the main component There are various (meth) acrylate-based adhesive substances and polyether-based thickening substances such as polyethylene oxide. Hydrophilic atopic dermatitis for external preparation and is added to the extent that does not affect the parent alcoholic.

The deep water used in the present invention is preferably deep water known to be effective for treating atopic dermatitis, particularly deep sea water deeper than 100 m, for example, deep sea water deeper than 100 m. What is drawn up by a known suction pump from the tips of various pipes installed toward each other is used. The amount of the deep water blended varies depending on the intended therapeutic effect or physical constraints such as solubility,
The cross-linked (co) polymer is blended in an amount of 1 to 90 parts by weight with respect to 100 parts by weight of a preparation prepared by dissolving the crosslinked (co) polymer in water and alcohols. It is particularly preferably 5 to 40 parts by weight. If it is less than 1 part by weight, the concentration of deep water in the composition is too low to obtain sufficient absorbability, and if it exceeds 90 parts, the skin is irritated.

Further, for the purpose of promoting absorption of deep water from the gel preparation obtained by the present invention, salicylic acid, salicylic acid derivatives, keratin softening agents such as urea and sulfur, moisturizing agents such as pyrrolidonecarboxylic acid, propylene glycol mono Surfactants such as oleate, polyoxyethylene sorbitan monostearate, sorbitan monostearate and glycerin monostearate, esters such as isopropyl myristate and diethyl sebacate, higher alcohols such as oleyl alcohol, stearyl alcohol and lauryl alcohol Higher fatty acids such as oleic acid, stearic acid, allantoin, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, diisopropyl adipate, diethyl sebacate, ethyl laurate, lanolin, ray Auxiliaries such as diamine, diphenhydramine hydrochloride, isothibenzyl hydrochloride and other antihistamines, antipruritic agents such as crotamiton, anti-inflammatory agents such as glycyrrhetinic acid and dipotassium glycyrrhizinate, cooling agents such as menthol and camphor, and fluids. One or more types of oil components such as paraffin and neutralizing agents such as diisopropanolamine can be blended, but considering the skin irritation and the like, the blending amount is 0.
It is desirable that the amount be 1 to 5 parts by weight.

The crosslinked (co) polymer used in the present invention exhibits more of its properties, and further has improved processability / moldability and quality of the preparation, and improved dispersibility and stability of deep water. For the above purpose, a product selected from pharmaceutically acceptable additives according to the purpose can be further arbitrarily blended. The additives include medicines, stabilizers, fillers, ultraviolet absorbers, fragrances, colorants, usability improvers, preservatives, preservatives, plasticizers, antioxidants, softeners, pH adjusters, and deterioration prevention. There are agents, etc. These additives are optionally added within a range that does not affect the properties of the resulting deep water-containing gel base.

To obtain a gel preparation in the present invention, an aqueous solution of N-vinylacetamide cross-linking (co) polymer and / or a solvent solution and deep water, and optionally various additives are mixed in the presence of water and / or a solvent. , If necessary, heat to dissolve. Crosslinking of N-vinylacetamide (co)
The amount of the polymer compounded is selected from the range of 0.5 to 20 parts by weight, preferably 1 to 5 parts by weight, based on the preparation. Cross-linking (co)
If the blending amount of the polymer is less than 0.5 part by weight, dripping occurs at the time of application, and if it exceeds 20 parts by weight, the viscosity is too high and the spreadability is deteriorated and the usability is unfavorable.

The method for producing the crosslinked (co) polymer used in the present invention may be any conventionally known method, for example, reverse phase suspension polymerization in which an aqueous monomer solution is dispersed in an organic solvent, The monomer component dissolves, but the polymer obtained from the monomer component does not dissolve. In an aqueous organic solvent or an organic solvent, the monomer component is uniformly dissolved to carry out a polymerization reaction. How to get coalesced, also
In some cases, azo compounds such as azobisisobutyronitrile, 2,2′-azobis-2-amidinopropane hydrochloride, t-, etc., using water, methanol, ethanol, other organic solvent or a mixture thereof as a solvent. Butyl peroxide, hydrogen peroxide, t-amyl peroxide, cumyl peroxide, acetyl peroxide, propionyl peroxide, benzoyl peroxide, benzoyl isobutyyl peroxide, lauroyl peroxide, t-butyl hydroperoxide, cyclohexyl Hydroperoxide, a peroxide such as tetralin hydroperoxide, can be polymerized using a radical polymerization initiator such as a so-called redox initiator in which a persulfate and an organic amine are combined, but preferably water is used as a solvent. When Then, it is desirable to polymerize with a water-soluble azo compound as an initiator. The polymerization initiation temperature varies depending on the type of the initiator used, but is usually 0 to 100 ° C,
It is preferably in the range of 10 to 70 ° C. The reaction is performed after degassing with nitrogen gas, argon gas, or the like, but is preferably performed in a nitrogen gas atmosphere. The reaction product is solidified by a precipitation operation using a water-soluble solvent such as acetone or an evaporation operation of the solvent, and then provided for use.

[0024]

The deep water-containing gel preparation of the present invention contains N- in the base.
By using a homo-crosslinked polymer or a crosslinked copolymer of vinylacetamide, especially N-vinylacetamide, (1) the base polymer is nonionic or weakly anionic, so the gel strength is reduced by the salts of deep water. Without
Excellent percutaneous absorption of deep water. (2) It does not form a complex with salts, which are the active ingredients of deep water, and excels in the release of salts from gel preparations. (3) It is possible to provide a gel preparation with high safety and long-lasting effect.

[0025]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but it goes without saying that the technical scope of the present invention is not limited to the following contents. In the following, “parts” means “parts by weight”.

Production Example of Crosslinked (Co) Polymer Production Example 1 A 1-liter four-necked separable flask was equipped with a stirring blade, a thermometer, a nitrogen introducing tube and a stopper, and 70 g of N-vinylacetamide was added thereto. Cross-linking agent pentaerythritol triallyl ether 1.05g, ethyl acetate 630g,
The N-vinyl acetamide was dissolved. Nitrogen gas was introduced to drive out dissolved oxygen, and the mixture was stirred, and polymerization initiator dimethyl 2,2′-azobis (2-propionate) 0.4 was added.
A solution of 9 g dissolved in about 5 ml of ethyl acetate was added to the reactor. The temperature of the inner solution was raised to 70 ° C., and polymerization was performed at this temperature for 5 hours. As the N-vinylacetamide polymer is deposited as a precipitate with the progress of the polymerization, the N-vinylacetamide polymer is filtered by filtering the inner solution after the completion of the polymerization.
I got After washing this polymer several times with ethyl acetate,
It was dried in a vacuum dryer at 50 ° C. for 14 hours to obtain a white fine powder of crosslinked polymer. Particle size is 10μm or less, viscosity is 1
% Aqueous solution was 200 cps.

Production Example 2 A 1-liter four-necked separable flask was equipped with stirring blades, a thermometer, a nitrogen inlet tube, and a stopper, to which 49 g of N-vinylacetamide, 21 g of acrylic acid, and 1 crosslinker of divinylbenzene were added. 0.05 g and ethyl acetate 630 g were added, and N-
Vinyl acetamide was dissolved. Stirring while introducing nitrogen gas and expelling dissolved oxygen, polymerization initiator dimethyl 2,2′-azobis (isobutyronitrile) 0.49 g
Was dissolved in about 5 ml of ethyl acetate and added to the reactor. The temperature of the inner solution was raised to 70 ° C., and polymerization was performed at this temperature for 5 hours. As the N-vinylacetamide acrylic acid copolymer precipitates as the polymerization proceeds,
After the completion of the polymerization, the inner solution was filtered to obtain an N-vinylacetamide acrylic acid copolymer polymer. The polymer was washed several times with ethyl acetate and then dried in a vacuum dryer at 50 ° C., 14 ° C.
After drying for an hour, a white fine powder of the crosslinked polymer was obtained. This polymer was once dispersed in water and neutralized to pH 7.0 with sodium hydroxide to obtain a viscous liquid. As a result of measuring the viscosities of 0.2% and 1% aqueous solutions of this viscous liquid,
It was 256 cps and 104,000 cps.

Production Example 3 A 1-liter four-necked separable flask was equipped with a stirring blade, a thermometer, a nitrogen introducing tube, and a stopper, and 38.5 g of N-vinylacetamide and 31. (meth) acrylic acid were added thereto. 5
g, crosslinking agent divinylbenzene 1.05 g, ethyl acetate 6
30 g was added and N-vinyl acetamide was dissolved. Stir while introducing nitrogen gas to drive out dissolved oxygen,
A solution prepared by dissolving 0.49 g of polymerization initiator dimethyl 2,2'-azobis (2-propionate) in about 5 ml of ethyl acetate was added to the reactor. The temperature of the inner solution was raised to 70 ° C., and polymerization was performed at this temperature for 5 hours. N- with the progress of polymerization
Vinylacetamide (meth) acrylic acid copolymerization polymer
As a precipitate, a solution of N-vinylacetamide / (meth) acrylic acid copolymer was obtained by filtering the inner solution after the completion of the polymerization. After washing the polymer several times with ethyl acetate, it was dried in a vacuum dryer at 50 ° C. for 14 hours to obtain a white fine powder crosslinked polymer. This polymer was once dispersed in water, and the pH was adjusted to 7.0 with potassium hydroxide.
A viscous solution was obtained by neutralizing the solution. 0.2% of this viscous liquid
And the viscosity of the 1% aqueous solution was measured to be 198 cps,
It was 78600 cps.

Comparative Preparation Example 1 As a monomer, 20.0 parts of N-vinylacetamide and 80.0 parts of acrylic acid were used. Thereafter, the same procedure as in Preparation Example 2 was followed to neutralize the mixture to pH 7.0 with sodium hydroxide to obtain a viscous solution. Got

Changes in Physical Properties of Crosslinked (Co) Polymers with Deep Water Preparation Examples, Comparative Preparation Examples and 20 g of a 10% deep aqueous solution (depth: 500 m) of carboxyvinyl polymer (Carbopol 934BF Goodrich) were prepared. The gel is a glass sample bottle SV-50 (Nikden Science Glass)
The mixture was placed in a container, capped, and allowed to stand at 40 ° C. for 6 months, and the cream strength was measured with time. The cream strength was measured as the maximum stress (g) when a sensitive axis (aluminum cylinder, diameter 10 mm, height 12 mm) was allowed to enter the gel at a moving distance of 30 mm and a moving speed of 5 mm / sec. The measurement was performed at room temperature, and the number of measurements was five.

[0031]

[Table 1]

Example 1 10 g of the polymer obtained in Production Example 1 was dissolved in 70 g of purified water and 20 g of deep water collected at a depth of 100 m, and kneaded sufficiently until the whole became uniform to obtain a gel ointment. . As the deep sea water used below, water deeply pumped by a known suction pump from the tip of an iron wire armored hard polyethylene pipe having an inner diameter of 13 cm installed toward the sea at each depth was used. Deep water (depth 100 m) 20 g Polymer of Production Example 1 10 g Purified water 70 g

Example 2 1 g of the polymer obtained in Production Example 2 and 4 g of the polymer obtained in Production Example 3 were dissolved in 70 g of purified water and 6 g of deep water collected at a depth of 500 m, and kneaded thoroughly until the whole became uniform. To meet. Then, a mixed solution of 5 g of 1,3-butanediol, 1 g of crotamiton and 13 g of isopropanol was added and kneaded to obtain a gel ointment. Deep water (depth of 500 m) 6 g Polymer of Production Example 1 1 g Polymer of Production Example 4 4 g Wetting agent (1,3-butanediol) 5 g Purified water 70 g Antipruritic agent (crotamiton) 1 g Alcohol (isopropanol) 13 g

Example 3 2 g of the polymer obtained in Production Example 1 was added to 75 g of purified water at a depth of 32.
It was dissolved in a mixed solution of 20 g of deep water collected at 0 m, 1 g of ethanol and 2 g of glycerin, and kneaded sufficiently until the whole became uniform to obtain a gel preparation. Deep water (depth 320 m) 20 g Polymer of Production Example 1-2 g Wetting agent (glycerin) 2 g Purified water 75 g Alcohol (ethanol) 1 g

Example 4 1.5 g of the polymer obtained in Production Example 2 and 2 g of hydroxypropyl cellulose (pharmaceutical) were dispersed in 20 g of polyethylene glycol (# 400), and this solution was added to 70 g of deep water collected at a depth of 320 m and It was dissolved in a mixed solution of 6.5 g of purified water and kneaded sufficiently until the whole became uniform to obtain a cream. Deep water (depth 320 m) 70 g Polymer of Production Example 2 1.5 g Hydrophilic polymer (HPC) 2.0 g Wetting agent (PEG # 400) 20 g Purified water 6.5 g

Comparative Example 1 In order to compare with Example 4, a gel preparation was prepared in the same manner as in Example 4 except that the surface water of the ocean (3 m in depth) was used instead of the deep water in the same amount. Obtained. Surface water (depth 3 m) 70 g Polymer of Production Example 2 1.5 g Hydrophilic polymer (HPC) 2 g Wetting agent (PEG # 400) 20 g Purified water 6.5 g

Comparative Example 2 In order to compare with Example 3, the formulation amount was increased and the formulation was carried out in the same manner as in Example 3 to obtain a gel formulation. Deep water (depth 320 m) 95 g Polymer of Production Example 1-2 g Wetting agent (glycerin) 2 g Alcohol (ethanol) 1 g

Comparative Example 3 For comparison with Example 3, a carboxyvinyl polymer (Carbopol 934) was used instead of the polymer of Production Example 1.
BF Goodrich Co., Ltd.) was used to prepare a gel preparation by the same method as in Example 3, but the cream strength decreased with time and the usability deteriorated. Surface water (depth 320 m) 20 g CVP934 2 g Wetting agent (glycerin) 2 g Purified water 75 g Alcohol (ethanol) 1 g

COMPARATIVE EXAMPLE 4 The polymer obtained in Comparative Production Example 1 was used in the same manner as in Example 1 to prepare a gel formulation for comparison with Example 1. As a result, the gel preparation as in Example 1 could not be obtained. Deep water (depth 100 m) 20 g Polymer of Comparative Production Example 1 10 g Purified water 70 g

Comparative Example 5 For the purpose of comparison with Example 3, compounding was carried out by the following method without adding a polymer. 77 g of purified water, 20 g of deep water collected at a depth of 320 m, 1 g of isopropanol, and 2 g of glycerin were sufficiently mixed to obtain a lotion agent. Deep water (depth 320m) 20g Wetting agent (glycerin) 2g Purified water 77g Alcohol (isopropanol) 1g

Confirmation of Safety When 0.1 to 0.3 g of the gel preparation obtained in Examples 1 to 3 was applied to the outside and the inside of the arm of 20 healthy persons for 1 to 3 consecutive days, No abnormality was observed in any of the 20 examiners. Clinical example Patient Female 26 years old This patient was naturally suffering from atopic dermatitis, the skin was dry and dry, and all the prescriptions were tried, especially on the neck and around the mouth, inside the ears and elbow joints. Also had no effect. As a result of applying the gel preparation of Example 3 and the preparations of Comparative Examples 1, 2 and 5 to the affected area twice a day respectively after waking up and after taking a bath, the gel preparation of Example 3 gradually showed pain and itchiness. It disappeared and the effect lasted for 12 hours. On the other hand, the preparations of Comparative Examples 1, 2 and 5 had no effect at all, and in Comparative Example 2, even the symptoms of worsening itching were observed. Therefore, application of the gel formulations of Comparative Examples 1, 2 and 5 was stopped in 3 days, and the gel formulations of Example 3 were switched to. After that, it was used daily for one month, but no side effect was observed, and the pruritus, swelling and pain of atopic dermatitis recovered considerably from before the prescription.

[0042]

INDUSTRIAL APPLICABILITY The deep sea water-containing gel preparation of the present invention can contain deep sea water at a high concentration and has excellent adhesion to the skin.
It is a gel preparation with a good feeling in use. It is possible to efficiently percutaneously absorb deep sea water, which is effective in treating skin diseases, particularly atopic dermatitis.

Claims (5)

[Claims] 1. A compound represented by the following general formula (1) CH ₂ ═CH—NR ¹ —COR ² (1) (wherein R ¹ and R ² independently represent a hydrogen atom or a methyl group). A deep sea water containing a cross-linked product of a polymer of which is a monomer or a cross-linked product of a copolymer of a monomer copolymerizable with the compound and deep sea water, and gelled. Gel formulation. 2. The compound represented by the general formula (1) is N-vinylacetamide, and the copolymerizable monomer is represented by the following general formula (2) CH ₂ ═CR-COOM (2) (wherein The deep seawater-containing gel preparation according to claim 1, wherein R is a hydrogen atom or a methyl group, and M is a hydrogen atom or an alkali metal atom.). 3. The deep sea water-containing gel preparation according to claim 1, wherein the crosslinked product of the polymer or the crosslinked product of the copolymer is in the form of fine particles having an average particle size of 10 μm or less. 4. The deep sea water-containing gel preparation according to claim 1, which contains 5 to 20 parts by weight of a polymer cross-linked product or a copolymer cross-linked product and 1 to 90 parts by weight of deep sea water. 5. The deep sea water-containing gel preparation according to claim 1, wherein the dosage form is a cream.