JP2023024628A - External agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external agent that has a high percutaneous absorption rate of medicinal components, and prevents the medicinal components from losing from the skin due to the external force of friction against e.g. skin and clothing or the movement of skin.

SOLUTION: An external agent contains component (a), component (b) and component (c), where, a composition containing component (a), component (b) and component (c) is directly electrostatically sprayed to skin to form a coat on the skin. (a) one or more volatile material selected from water, alcohol and ketone, (b) a polymer having a coat forming ability, (c) a transdermally administrable medicinal component.

SELECTED DRAWING: None

COPYRIGHT: (C)2023,JPO&INPIT

Description

The present invention relates to an external medicine that forms a film on the skin.

As transdermal medicines, topical drugs such as ointments, creams, gels and liquids, and patches such as poultices and tapes are mainly used. For these topical drugs, percutaneous absorption of medicinal ingredients is promoted by blending absorption-enhancing ingredients (Patent Documents 1, 2, etc.).

On the other hand, Patent Documents 3 to 5 describe a method of forming a film by electrostatic spraying.

WO2000/061120 WO2001/007018 JP 2006-104211 A Japanese Patent Publication No. 2000-516130 JP 2014-55119 A

However, in the case of topical drugs for application, the topical drugs applied on the skin often disappear from the application site due to contact with the skin, clothing, etc., and sufficient effects cannot be obtained in many cases. In addition, in the case of patches, since the medicinal ingredients are contained in the base such as the matrix of the patch, the rate of release from the base to the skin surface is not sufficiently high, so rapid percutaneous absorption is not possible. often not done.

The method of treating skin by electrostatic spraying described in US Pat. No. 5,900,005 is a method of treating skin by electrostatic application of particles, which are particulate powder substances. Therefore, since the film is not a deposit of fibers, it is difficult to maintain the form of a single film, the durability is poor such that particles partially fall off during use, and it is difficult to peel off after use.
On the other hand, in the method of forming a coating by electrostatic spraying described in Patent Document 4, since the coating formed is a deposit of fibers, it can be handled as a single sheet and can be easily peeled off after use. However, the adhesion between the coating formed by electrostatic spraying and the substrate is not sufficient, and the coating may be damaged or peeled off due to external forces such as friction. Furthermore, in Patent Document 4, it is related to covering the skin with a film made of deposits of fibers with good adhesion, making the film transparent and covering the skin in a natural state, and increasing the drug release and percutaneous absorption rate. , nothing is mentioned. In addition, the drug-containing ultrafine fiber described in Patent Document 5 relates to a method for producing an adhesive patch, not a method for forming a film on the skin.

Accordingly, an object of the present invention is to provide a topical drug that has a high rate of percutaneous absorption of a medicinal ingredient and that does not lose the medicinal ingredient from the skin due to external forces such as friction with the skin or clothes or movement of the skin. to provide.

As a result of various studies aimed at solving the above problems, the present inventors have developed a composition containing (a) a volatile substance, (b) a film-forming polymer, and (c) a medicinal ingredient that can be transdermally administered. If the skin is electrostatically sprayed directly to form a film on the skin, the film formed on the skin becomes a deposit of fibers and is easily destroyed by contact with clothing, skin, or water. The present inventors have found that it is possible to obtain an external medicine that does not peel off even when the skin is flexed and stretched, and has excellent percutaneous absorbability, thus completing the present invention.

That is, the present invention provides an external medicine containing component (a), component (b) and component (c), wherein the composition containing component (a), component (b) and component (c) is applied to the skin. To provide an external medicine which is used by electrostatically spraying directly onto the skin to form a film on the skin.
(a) one or more volatile substances selected from water, alcohols and ketones;
(b) a polymer with film-forming ability;
(c) A medicinal ingredient that can be transdermally administered.

By using the topical preparation of the present invention, a film having a high percutaneous absorption rate of the medicinal ingredient is formed on the skin. In addition, the formed film is not easily destroyed by contact with the skin or clothes, and is not peeled off by bending and stretching of the skin. In addition, the formed film is transparent and does not look like a patch.

FIG. 1 is a schematic diagram showing the configuration of an electrostatic spray device suitable for use in the present invention. FIG. 2 is a schematic diagram showing how the electrostatic spray method is performed using an electrostatic spray device.

The topical medicine of the present invention uses a composition containing component (a), component (b) and component (c) (hereinafter also referred to as composition for spraying).
(a) one or more volatile substances selected from water, alcohols and ketones;
(b) a polymer with film-forming ability;
(c) A medicinal ingredient that can be transdermally administered.

The volatile substance of component (a) is a substance that is volatile in its liquid state. In the composition for spraying, component (a) is discharged from the tip of the nozzle toward the skin after sufficiently charging the composition for spraying placed in an electric field, and component (a) evaporates. , the charge density of the composition for spraying becomes excessive, component (a) further evaporates while becoming finer due to Coulomb repulsion, and finally a dry film is formed on the skin. For this purpose, the vapor pressure of the volatile substance at 20° C. is preferably 0.01 kPa or more and 106.66 kPa or less, more preferably 0.13 kPa or more and 66.66 kPa or less. It is more preferably 67 kPa or more and 40.00 kPa or less, and even more preferably 1.33 kPa or more and 40.00 kPa or less.

Among the volatile substances of component (a), as alcohols, for example, monohydric chain aliphatic alcohols, monohydric cycloaliphatic alcohols, and monohydric aromatic alcohols are preferably used. Monohydric chain fatty alcohols are C ₁ -C ₆ chain chain fatty alcohols, monohydric cycloaliphatic alcohols are C ₄ -C ₆ cyclic alcohols, monohydric aromatic alcohols are includes benzyl alcohol, phenylethyl alcohol and the like. Specific examples thereof include ethanol, isopropyl alcohol, butyl alcohol, phenylethyl alcohol, n-propanol, n-pentanol and the like. One or two or more selected from these alcohols can be used.

Among the volatile substances of component (a), ketones include di-C ₁ -C ₄ alkyl ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone and the like. These ketones can be used singly or in combination of two or more.

The volatile substance of component (a) is more preferably one or more selected from ethanol, isopropyl alcohol, butyl alcohol and water, more preferably one or more selected from ethanol and butyl alcohol. and most preferably ethanol.

The content of component (a) in the spray composition is preferably 50% by mass or more, more preferably 55% by mass or more, and even more preferably 60% by mass or more. The content is preferably 98% by mass or less, more preferably 96% by mass or less, and even more preferably 94% by mass or less. The content of component (a) in the composition for spraying is preferably 50% by mass or more and 98% by mass or less, more preferably 55% by mass or more and 96% by mass or less, and 60% by mass or more and 94% by mass. The following are more preferable. By containing the component (a) in the composition for spraying in this proportion, the composition for spraying can be sufficiently volatilized when the electrostatic spraying method is carried out.

The film-forming polymer of component (b) is generally a substance that can be dissolved in the volatile substance of component (a). Here, "dissolved" means that it is in a dispersed state at 20° C., and that the dispersed state is visually uniform, preferably visually transparent or translucent.

As the film-forming polymer, an appropriate one is used depending on the nature of the volatile substance of component (a). Specifically, polymers having film-forming ability are broadly classified into water-soluble polymers and water-insoluble polymers. As used herein, the term "water-soluble polymer" means that 1 g of the polymer is weighed in an environment of 1 atm and 23° C., immersed in 10 g of deionized water, and after 24 hours, 0.0% of the immersed polymer is removed. 5g or more of those that have the property of being dissolved in water. On the other hand, the term "water-insoluble polymer" as used herein means that 1 g of the polymer was weighed in an environment of 1 atm and 23° C. and then immersed in 10 g of ion-exchanged water for 24 hours. .5 g or more of a substance that does not dissolve.

Examples of water-soluble polymers having film-forming ability include pullulan, hyaluronic acid, chondroitin sulfate, poly-γ-glutamic acid, modified corn starch, β-glucan, glucooligosaccharide, heparin, mucopolysaccharides such as keratosulfate, cellulose, and pectin. , xylan, lignin, glucomannan, galacturonic acid, psyllium seed gum, tamarind seed gum, gum arabic, tragacanth gum, soybean water-soluble polysaccharide, alginic acid, carrageenan, laminaran, agar (agarose), fucoidan, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl Examples include natural polymers such as methyl cellulose, partially saponified polyvinyl alcohol (when not used in combination with a cross-linking agent), low saponified polyvinyl alcohol, polyvinylpyrrolidone (PVP), polyethylene oxide, synthetic polymers such as sodium polyacrylate. These water-soluble polymers can be used alone or in combination of two or more. Among these water-soluble polymers, pullulan and synthetic polymers such as partially saponified polyvinyl alcohol, low-saponified polyvinyl alcohol, polyvinylpyrrolidone and polyethylene oxide are preferably used from the viewpoint of easy production of the coating. When polyethylene oxide is used as the water-soluble polymer, its number average molecular weight is preferably 50,000 or more and 3,000,000 or less, and more preferably 100,000 or more and 2,500,000 or less.

On the other hand, the water-insoluble polymer having film-forming ability includes, for example, fully saponified polyvinyl alcohol that can be insolubilized after film formation, partially saponified polyvinyl alcohol that can be crosslinked after film formation by using a crosslinking agent, and poly(N-propane). noylethyleneimine) graft-dimethylsiloxane/γ-aminopropylmethylsiloxane copolymer, oxazoline-modified silicone, polyvinyl acetal diethylaminoacetate, twein (main component of corn protein), polyester, polylactic acid (PLA), polyacrylonitrile resin, Examples include acrylic resins such as polymethacrylic acid resins, polystyrene resins, polyvinyl butyral resins, polyethylene terephthalate resins, polybutylene terephthalate resins, polyurethane resins, polyamide resins, polyimide resins, polyamideimide resins, and the like. These water-insoluble polymers can be used alone or in combination of two or more. Among these water-insoluble polymers, fully saponified polyvinyl alcohol that can be insolubilized after film formation, partially saponified polyvinyl alcohol that can be crosslinked after film formation by using a crosslinking agent, polyvinyl butyral resin, and (alkyl acrylate/octylamide) It is preferable to use acrylic resins such as polymers, oxazoline-modified silicones such as poly(N-propanoylethyleneimine) graft-dimethylsiloxane/γ-aminopropylmethylsiloxane copolymer, polyvinyl acetal diethylaminoacetate, twein, and the like.

The content of component (b) in the composition for spraying is not particularly limited as long as the electrostatic spray can be stably performed, but it is preferably 0.5% by mass or more, and preferably 2% by mass or more. More preferably, it is more preferably 4% by mass or more. The content is preferably 50% by mass or less, more preferably 40% by mass or less, and even more preferably 9% by mass or less. The content of component (b) in the composition for spraying is preferably 0.5% by mass or more and 50% by mass or less, more preferably 2% by mass or more and 40% by mass or less, and 4% by mass or more. % by mass or less is more preferable. By blending the component (b) in the composition for spraying in this ratio, a film consisting of a deposit of fibers and having excellent abrasion resistance and bending resistance and good release of the medicinal ingredient can be successfully formed. can do.

Component (c) is a medicinal ingredient that can be transdermally administered. Such medicinal ingredients include α-adrenergic receptor blockers, adrenergic receptor stimulants, angiotensin II receptor antagonists, angiotensin-converting enzyme inhibitors, calcium antagonists, steroidal anti-inflammatory/anti-inflammatory analgesics, Parkinson's disease treatment. Medicines, vitamin-related drugs, hormone drugs, drugs for athlete's foot and tinea (antifungal drugs), antipyretic analgesics, drugs for external hemorrhoids, coronary vasodilators, bronchodilators and antitussives, cardiotonic drugs, antianginal drugs, topical Anesthetics, hypoglycemic agents, oropharyngeal agents, psychotropic agents, antiallergic agents, antihistamines, antibacterial agents, antiparasitic/anthelmintic/insecticide agents, antiarrhythmic agents, antiemetic agents, antihyperlipidemic agents, bactericidal agents Medicines, hemostatic drugs, drugs for women, antiseptics, sleeping pills, tissue respiration activators, antipruritic anti-inflammatory drugs, isotonic solutions, skin disease therapeutic agents, non-steroidal anti-inflammatory/anti-inflammatory analgesics, moisturizers, erectile dysfunction drugs, Anesthetics, peripheral vasodilators, immunosuppressants, hair preparations, diuretics, enemas, smoking cessation aids. Among them, adrenergic receptor stimulants, steroidal anti-inflammatory/anti-inflammatory analgesics, vitamin-related drugs, external hemorrhoidal drugs, bronchodilators/antitussives, local anesthetics, oropharyngeal drugs, psychotropic drugs, anti-allergic drugs, antihistamines Medicines, antibacterial agents, antiparasitic/anthelmintic/insecticides, bactericidal agents, hemostatic agents, medicines for women, antiseptics, tissue respiration activators, antipruritic anti-inflammatory agents, isotonic solutions, skin disease therapeutic agents, non-steroidal anti-inflammatory agents At least one selected from antiphlogistic analgesics, moisturizers, anesthetics, immunosuppressants, and hair preparations is preferred.

Alpha-adrenergic receptor blockers include urapidil, terazosin hydrochloride, bunazosin hydrochloride, prazosin hydrochloride, doxazosin mesylate, bisoprolol fumarate, propranolol hydrochloride, tilisolol hydrochloride, bufetrol hydrochloride, bupranolol hydrochloride, atenolol, indenolol hydrochloride, alprenolol hydrochloride, oxprenolol hydrochloride, carteolol hydrochloride, nadolol, pindolol, timolol maleate, nipradilol, bunitrolol hydrochloride, penbutolol sulfate, bopindolol malonate, Metoprolol tartrate, betaxolol hydrochloride, bevantolol hydrochloride, acebutolol hydrochloride.

Adrenergic receptor agonists include epinephrine, norepinephrine, dopamine hydrochloride, phenylephrine hydrochloride, etilephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, clonidine hydrochloride, methyldopa, guanabenz acetate, guanfacine hydrochloride, isoprenaline hydrochloride , methoxyphenamine hydrochloride, orciprenaline sulfate, chlorprenaline hydrochloride, trimetoquinol hydrochloride, salbutamol sulfate, terbutaline sulfate, hexoprenaline sulfate, tulobuterol hydrochloride, fenoterol hydrobromide, procaterol hydrochloride, Clenbuterol hydrochloride, mabuterol hydrochloride, isoxsuprine hydrochloride, methamphetamine hydrochloride, methylphenidate hydrochloride, pemoline, imipramine hydrochloride, amezinium methyl sulfate. Among these, at least one selected from ephedrine hydrochloride is preferred.

Angiotensin II receptor antagonists include losartan potassium, candesartan, candesartan cilexetil, olmesartan medoxomil, irbesartan.

Angiotensin-converting enzyme inhibitors include alacepril, captopril, delapril hydrochloride, quinapril hydrochloride, benazepril hydrochloride, cilazapril hydrate, enalapril maleate, trandolapril, imidapril hydrochloride, lisinopril hydrate, and perindopril erbumine. , temocapril hydrochloride, and ramipril.

Calcium antagonists include verapamil hydrochloride, diltiazem hydrochloride, bepridil hydrochloride, clenchazem, nifedipine, nicardipine hydrochloride, felodipine, nisoldipine, cilnidipine, aranidipine, benidipine hydrochloride, manidipine hydrochloride, nilvadipine, nitrendipine, and barnidipine hydrochloride. , efonidipine hydrochloride.

Steroidal anti-inflammatory/anti-inflammatory analgesics include hydrocortisone butyrate, prednisolone valerate acetate, methylbrednisolone, hydrocortisone acetate, fluocinolone acetonide, triamcinolone acetonide, dexamethasone, betamethasone valerate, and diflucort. ronvalerate, clobetasol propionate, fluocinonide, halcinonide, dexamethasone acetate, dexamethasone acetate, tetrahydrozoline hydrochloride, amcinonide, alclomethasone propionate, clobetasone butyrate, difluprednate, diflorazone acetate, dexamethasone valerate , deprodone propionate, prednisolone, prednisolone acetate, dexamethasone propionate, betamethasone dipropionate, mometasone furoate, hydrocortisone butyrate propionate, betamethasone butyrate propionate. and, among these, hydrocortisone butyrate, prednisolone valerate acetate, fluocinolone acetonide, triamcinolone acetonide, dexamethasone, diflucortolone valerate, clobetasol propionate, fluocinonide, halcinonide, dexamethasone acetate, hydrochloric acid Tetrahydrozoline, amcinonide, alclomethasone propionate, clobetasone butyrate, difluprednate, diflorazone acetate, dexamethasone valerate, deprodone propionate, prednisolone, prednisolone acetate, dexamethasone propionate, betamethasone dipropionate More preferably, at least one selected from esters, mometasone furoate, hydrocortisone butyrate propionate, betamethasone butyrate propionate.

Parkinson's disease drugs: trihexyphenidyl hydrochloride, profenamine hydrochloride, pyroheptine hydrochloride, mazaticol hydrochloride, methixene hydrochloride, biperiden hydrochloride, amantadine hydrochloride, levodopa, carbidopa, benseraside, droxidopa, bromocriptine mesylate , talipexole hydrochloride, cabergoline, pergolide mesylate, selegiline hydrochloride.

Vitamin-related drugs include vitamin A, vitamin D, vitamin E, vitamin K, phytonadione, alfacalcidol, eldecalcitol, calcitriol, falecalcitriol, retinol palmitate, ergocalciferol, cholecalciferol, and phosphoric acid. Calcium hydrogen, calcium hydrogen phosphate hydrate, retinol, calcium lactate, calcium lactate hydrate, tretinoin, refined eel oil, ascorbic acid, d-α-tocopherol, sodium L-ascorbate, calcium ascorbate, Sodium ascorbate, ascorbic acid powder, ascorbic acid powder, orotic acid, nicotinamide, vitamin C, riboflavin, riboflavin butyrate, direct ascorbic acid, calcium pantothenate, vitamin A oil, tocopherol, d-α-tocopherol succinate acid ester, d-α-tocopherol acetate, d-α-tocopherol succinate, calcium tocopherol succinate, nicotinic acid, pyridoxine hydrochloride, d-α-tocopherol acetate, d-α-tocopherol acetate powder, riboflavin butyrate, RIKEN Dry E-B500d-GP, panthenol, pyridoxine hydrochloride, retinol acetate, liver oil, strong liver oil, dl-α-tocopherol succinate, thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate, hydrochloric acid Disetiamine, fursultiamine hydrochloride, octotiamine, sicotiamine, bisivetiamine, bisbentiamine, fursultiamine, prosultiamine, benfotiamine, flavin adenine dinucleotide sodium, riboflavin sodium phosphate, pyridoxal phosphate, hydroxocobalamin hydrochloride , hydroxocobalamin acetate, cyanocobalamin, hydroxocobalamin, sodium pantothenate, biotin, potassium-magnesium aspartate mixture, inositol hexanicotinate, ursodesoxycholic acid, L-cysteine hydrochloride, L-cysteine, gamma oryzanol, calcium glycerophosphate , calcium gluconate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, glucuronolactone, glucuronic acid amide, sodium chondroitin sulfate, processed garlic, carrot, coix seed. And among these, vitamin A, phytonadione, alfacalcidol, eldecalcitol, calcitriol, falecalcitriol, retinol palmitate, ergocalciferol, cholecalciferol, calcium hydrogen phosphate, calcium hydrogen phosphate water Hydrate, retinol, calcium lactate, calcium lactate hydrate, tretinoin, refined eel oil, ascorbic acid, d-α-tocopherol, L-sodium ascorbate, calcium ascorbate, sodium ascorbate, ascorbic acid powder, Ascorbic acid powder, orotic acid, nicotinamide, vitamin C, riboflavin, riboflavin butyrate, direct ascorbic acid, calcium pantothenate, vitamin A oil, tocopherol, d-α-tocopherol succinate, d-α-tocopherol Acetate, d-α-tocopherol succinate, calcium tocopherol succinate, nicotinic acid, pyridoxine hydrochloride, d-α-tocopherol acetate, d-α-tocopherol acetate powder, riboflavin butyrate, Riken dry E-B500d-GP, bread At least one selected from tenol, pyridoxine hydrochloride, and L-cysteine is preferred.

Hormonal agents include estrogen, estradiol, testosterone, progesterone, insulin, prostaglandins.

For athlete's foot and ringworm (antimycotics), undecylenic acid, zinc undecylenate, phenyl-11-iodo-10-undecinoate, exalamide, clotrimazole, econazole nitrate, miconazole nitrate, tioconazole, zinc diethyldithiocarbamate, Ciclopirox olamine, siccanin, tricomycin, pyrrolnitrin, thianthol, 2,4,6-tribromophenylcaproate, trimethylcetylammonium pentachlorophenate, tricyclate, tolnaftate, haloprozin, tree bark ), berberine benzoate, dequalinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate solution, dequalinium acetate, hinokitiol, lebrucin, benzoic acid, chlorobutanol, acetic acid, phenol, iodine tincture, diphenylpyraline hydrochloride, diphenhydramine salicylate, diphenylimidazole, chlorphenyne maleate Lamin, dibucaine hydrochloride, procaine hydrochloride, lidocaine hydrochloride, aldioxa, glycyrrhizic acid and its salts, licorice (in terms of crude drug amount), Touki (in terms of crude drug amount), thymol, borneol, diethyl phthalate, aluminum chlorohydroxyl.

Antipyretic analgesics include aspirin sodium, ethenzamide, allyl isopropyl urea, caffeine sodium benzoate, caffeine, vitamin B1 and its derivatives and their salts, vitamin B2 and its derivatives and their salts, aminoacetic acid, magnesium silicate, synthesis Aluminum Silicate, Synthetic Hydrotalcite, Magnesium Oxide, Dihydroxy Aluminum Amino Acetate (Aluminum Glycinate), Aluminum Hydroxide Gel (as Dry Aluminum Hydroxide Gel), Dry Aluminum Hydroxide Gel, Chiryu, Glycyrrhiza, Citrus, Examples include peony, Japanese pepper, and ginger.

For external hemorrhoids, horse chestnut seed extract, ethyl aminobenzoate, diethylaminoethyl parabutylaminobenzoate hydrochloride, meprilcaine hydrochloride, oxypolyethoxide decane, rot extract, epinephrine solution, naphazoline hydrochloride, hydrocortisone, tannic acid, acrinol , alkylpolyaminoethylglycine, decalinium chloride, berberine chloride hydrate, cetrimide, resorcinol, sulfadiazine, sulfisomidine, sulfisomidine sodium, homosulfamine, chlorpheniramine maleate, aluminum chlorohydroxyallantoinate, ictamol , lysozyme chloride, dried aluminum potassium sulfate, refined egg yolk lecithin, egg yolk oil, aluminum potassium sulfate, horse chestnut seed, horse chestnut seed, hamamelis, processed daisan, d-camphor, dl-camphor, mint oil, dl-menthol. Among these, at least one selected from horse chestnut seed extract, d-camphor, dl-camphor, and dl-menthol is preferable.

Coronary vasodilators include etafenone hydrochloride, trimetazidine hydrochloride, trapidil, nicorandil.

As a bronchodilator/antitussive agent, dl-methylephedrine hydrochloride is preferred.

Cardiotonics include digitoxin, digoxin, methyldigoxin, lanatoside C, proscilaridine, dobutamine hydrochloride, docarpamine, denopamine, aminophylline hydrate, milrinone, vesnarinone, pimobendan, ubidecarenone.

Antianginal agents include amyl nitrite, nitroglycerin, isosorbide dinitrate, diracep hydrochloride, and dipyridamole.

Local anesthetics include lidocaine, mepivacaine, bupivacaine, ropivacaine, levopupivacaine. And among these, lidocaine is preferred.

Antihyperglycemic drugs include glibenclamide, gliclazide, glimepiride, repaglinide, nateglinide, mitiglinide calcium hydrate, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose, miglitol, pioglitazone hydrochloride, troglitazone.

As oropharyngeal drugs, chlorhexidine hydrochloride and sodium azulene sulfonate are preferred.

Psychotropics include chlorpromazine hydrochloride, perazine maleate, levomepromazine maleate, trifluoperazine hydrochloride, prochlorperazine maleate, perphenazine, fluphenazine maleate, thioridazine hydrochloride, thiothixene, carpipramine hydrochloride, clocapramine hydrochloride hydrate, mosapramine hydrochloride, zotepine, haloperidol, spiperone, timiperone, bromperidol, pimozide, oxypertine, sulpiride, sultopride hydrochloride, tiapride hydrochloride, nemonapride, perospirone hydrochloride, quetiapine fumarate , risperidone, olanzapine, propericiazine, clotiazepam, etizolam, alprazolam, lorazepam, bromazepam, chlordiazepoxide, diazepam, oxazolam, cloxazolam, fludiazepam, mexazolam, ethyl loflazepate, clomipramine hydrochloride, amitriptyline hydrochloride, nortriptyline hydrochloride, lofepramine hydrochloride salt, amoxapine, dosulepin hydrochloride, maprotiline hydrochloride, mianserin hydrochloride, setiptiline maleate, fluvoxamine maleate, paroxetine hydrochloride hydrate, milnacipran hydrochloride, trazodone hydrochloride, lithium carbonate, hydroxyzine pamoate , hydroxyzine hydrochloride. Among these, hydroxyzine pamoate and hydroxyzine hydrochloride are preferred.

Antiallergic drugs include pemirolast, cromoglycate sodium, tramalast, amlexanox, azelastine, ketotifen, mequitazine, fexofenadine, epinastine, epastine, cetirizine, levocetirizine, bepotastine, emedastine, olopatadine, loratadine, desloratadine, pilastine, pranlukast , montelukast, suplatast tosylate, tranilast. Among these, sodium cromoglycate, mequitazine, loratadine, suplatast tosylate and tranilast are preferred.

Antihistamines include diphenhydramine, chlorpheniramine, promethazine, hydroxyazine, cyproheptadine, clemastine, diphenylpyraline teocrate, diphenhydramine tannate, azelastine hydrochloride, epinastine hydrochloride, oxatomide, olopatadine hydrochloride, ketotifen fumarate. , diphenhydramine hydrochloride, cyproheptadine hydrochloride hydrate, fexofenadine hydrochloride, fumarate, bepotastine besilate, alimemazine tartrate, clemastine fumarate, chlorpheniramine maleate, diphenylpyraline hydrochloride, triplo Lysine hydrochloride hydrate, sodium riboflavin phosphate, homochlorcyclidine hydrochloride, ebastine, cetirizine hydrochloride, levocetirizine hydrochloride, emedastine fumarate. and, among these, diphenhydramine, promethazine, diphenylpyraline teocrate, diphenhydramine tannate, azelastine hydrochloride, epinastine hydrochloride, oxatomide, olopatadine hydrochloride, ketotifen fumarate, diphenhydramine hydrochloride, cyproheptadine hydrochloride hydrate , fexofenadine hydrochloride, bepotastine besilate, alimemazine tartrate, clemastine fumarate, chlorpheniramine maleate, diphenylpyraline hydrochloride, triprolidine hydrochloride hydrate, riboflavin sodium phosphate, homochlor Preferred are cyclizine hydrochloride, ebastine, cetirizine hydrochloride, levocetirizine hydrochloride, emedastine fumarate.

Antibacterial agents include penicillins, cephems, carbapenems, monobactams, penems, aminoglycosides, fosfomycins, chloramphenicol, macrolides, glycopeptides, quinolones, new quinolones, sulfa drugs, and fradiomycin. Sulfate, gentamicin sulfate, pentamidine isethionate, silver sulfadiazine. Among these, chloramphenicol, fradiomycin sulfate, gentamicin sulfate, pentamidine isethionate, and silver sulfadiazine are preferred.

Antiparasitic/anthelmintic/insecticides include 2-undecanone, p-menthane-3,8-diol, atovaquone/proguanil hydrochloride, icaridin, eugenonal, orange oil, geraniol, citral, citronellal, citronellol, and sulfamethoxa. Sol Trimethoprim, Pinene, Ethyl Butyl Acetyl Aminopropionate, Myrcene, Metofluthrin, Linalool, Limonene, Lemon Eucalyptus Essential Oil, Albendazole, Praziquantel, Phenothrin, Santonin, Pyrvinium Pamoate, Macri, Pyrantel Pamoate, Tinidazole, Quinine Hydrochloride Hydrate primaquine phosphate, mefloquine hydrochloride, diethylcarbamazine citrate, metronidazole, d,dT-cyphenothrin, amidoflumet, imiprothrin, orthodichlorobenzene, dichlorvos, diazinon, deet, trichlorfon, hydramethylnon, pipet Ronyl butoxide, pyriproxyfen, pyrethrin, fenitrothion, fenthion, phthalthrin, propetamphos, propoxur, permethrin, methoxadiazone, methoprene, benzyl benzoate, pyrethrum extract (total pyrethrins), paromomycin sulfate, ivermectin, mebendazole, kainate, adipine Piperazine acid, piperazine citrate, piperazine hexahydrate, piperazine malate, piperazine phosphate, sulfur, dioctyl sodium sulfosuccinate, aloe, senna, rhubarb, aminoethylsulfonic acid, bile extract (powder), bile powder, dehydro cholic acid, kurenpi, shikunshi, eucalyptus oil. Among these, p-menthane-3,8-diol, icaridin, ethyl butylacetylaminopropionate, and DEET are preferred.

Antiarrhythmic agents include quinidine sulfate hydrate, ajmaline, procainamide hydrochloride, disopyramide, pirmenol hydrochloride, cibenzoline succinate, mexiletine hydrochloride, propafenone hydrochloride, pilsicainide hydrochloride, sotalol hydrochloride, and amiodarone hydrochloride. is mentioned.

Anti-emetic agents include granisetron hydrochloride, azasetron hydrochloride, ondansetron hydrochloride, ramosetron hydrochloride, tropisetron hydrochloride.

Antihyperlipidemic agents include pravastatin sodium, simvastatin, fluvastatin sodium, atorvastatin calcium, rosuvastatin calcium, pitavastatin calcium, cuclofibrate aluminum, clinofibrate, bezafibrate, fenofibrate, nicomole, niceritrol, probucol, and ezetimibe. .

Chlorhexidine gluconate, sodium copper chlorophyllin, isopropylmethylphenol, cetylpyridinium chloride hydrate, benzethonium chloride, and benzalkonium chloride are preferred as bactericidal agents.

Hemostatic agents include tranexamic acid, warfarin potassium, heparin sodium, argatroban monohydrate, carbazochrome. Among these, tranexamic acid and carbazochrome are preferred.

As female drugs, DL-methionine, tocopherol powder (50%), and royal jelly are preferred.

Preferred disinfectants are iodine and cresol.

Hypnotics include flurazepam, haloxazolam, quazepam, nitrazepam, flunitrazepam, estazolam, nimetazepam, lormetazepam, rilmazafone hydrochloride, triazolam, midazolam, zopiclone, zolpidem tartrate, brotizolam, barbital, and amobarbital.

Solcoseryl is preferred as a tissue respiration activator.

Antipruritic and antiphlogistic drugs include crotamiton, cortisone acetate, isothipendyl hydrochloride, glycol salicylate, benzalkonium chloride, calamine, d-borneol and aqueous ammonia. And, among these, crotamiton is preferred.

Physiological saline is preferred as the isotonic solution.

As therapeutic agents for skin diseases, trafermin, etretinate, maxacalcitol, alcloxa, bucladesine sodium, alprostadil alfadex, tretinoin tocopheryl, and refined sucrose are preferred.

Non-steroidal anti-inflammatory/anti-inflammatory analgesics include salicylic acid, aspirin, sulpyrin hydrate, acetaminophen, diclofenac sodium, fenbufen, ibuprofen, aminoprofen, loxoprofen sodium hydrate, naproxen, oxaprofen, ketoprofen, tiaprofenic acid, sulindac, aluminum flufenamate, felbinac, mefenamic acid, indomethacin, indomethacin farnesyl, acemethacin, proglutamine maleate, bendazac, piroxicam, ampiroxicam, lornoxicam, tenoxicam, meloxicam, flurbibrofen, etodolac, tiaramide hydrochloride salt, bucolome, loxoprofen sodium, flurbiprofen, esflurbiprofen, methyl salicylate, lysozyme hydrochloride, bromelain, diphenhydramine hydrochloride, dibucaine, dimethylisopropylazulene, benzethonium chloride, dipotassium glycyrrhizinate, l-menthol, zinc oxide , allantoin, heparin analogs, and glycyrrhetinic acid. and among these, diclofenac sodium, loxoprofen sodium hydrate, ketoprofen, felbinac, indomethacin, piroxicam, loxoprofen sodium, flurbiprofen, esflurbiprofen, methyl salicylate, lysozyme hydrochloride, bromelain, l-menthol , zinc oxide, allantoin, heparinoids, and glycyrrhetinic acid are preferred.

Humectants include white petrolatum, glycerin, propylene glycol, 1,3-butylene glycol, sorbitol, pyrrolidone carboxylate, urea and hyaluronic acid. Among these, white petrolatum and glycerin are preferred.

Erectile dysfunction drugs include sildenafil citrate, vardenafil hydrochloride, and tadalafil.

Anesthetics include benzocaine, procaine hydrochloride, lidocaine hydrochloride, tetracaine hydrochloride, chloroprocaine, mepivacaine hydrochloride, dibucaine hydrochloride, bupivacaine hydrochloride, droperidol, fentanyl citrate. Among these, lidocaine hydrochloride and dibucaine hydrochloride are preferred.

Peripheral vasodilators include hydralazine hydrochloride, todralazine hydrochloride hydrate, budralazine, cadralazine, sodium nitroprusside.

Immunosuppressants include tacrolimus and tacrolimus hydrate. Among these, tacrolimus hydrate is preferred.

Carpronium chloride hydrate, finasteride, dutasteride, cashew tincture, ginseng tincture, and minoxidil are preferred as hair preparations.

Diuretics include benzoylhydrochlorothiazide, trichlormethiazide, methyclothiazide, ethacrynic acid, indapamide, chlorthalidone, tripamide, methicrane, mefluside, piretanide, furosemide, bumetanide, torasemide, azosemide, potassium canrenoate, spironolactone, triamterene, acetazolamide. be done.

Enemas include D-sorbitol and bisacodyl.

Smoking cessation aids include nicotine.

The medicinal ingredients can be used singly or in combination of two or more depending on the application of the external preparation (A). For example, in the case of an anti-inflammatory and analgesic topical agent, a steroidal anti-inflammatory/anti-inflammatory analgesic, a non-steroidal anti-inflammatory/anti-inflammatory analgesic, a local anesthetic, a vitamin-related drug, a cooling agent such as menthol, etc. should be combined. can be done. In the case of external preparations for infectious skin diseases, antibacterial drugs, cooling agents, steroidal anti-inflammatory drugs and the like can be used in combination. Topical agents for atopic skin treatment include steroidal anti-inflammatory/anti-inflammatory analgesics, non-steroidal anti-inflammatory/anti-inflammatory analgesics, local anesthetics, immunosuppressants, antihistamines, anti-allergic agents, moisturizers, and vitamins. It can be compounded by combining drugs and the like. In the case of drugs for athlete's foot and ringworm, antifungal agents, antihistamines, local anesthetics, etc. can be combined. In the case of external preparations for hemorrhoids, steroidal anti-inflammatory agents, hemostatic agents, non-steroidal anti-inflammatory/anti-inflammatory analgesics, antihistamines and the like can be used in combination.

Among these components (c), nonsteroidal anti-inflammatory/anti-inflammatory analgesics are preferred from the viewpoint of more effectively utilizing the effects of the present invention, and are selected from felbinac, diclofenac or salts thereof, loxoprofen, and flurbiprofen. At least one or two are more preferred. In addition, component (c) can be used alone or in combination of two or more depending on its use.
According to the present invention, even if the medicinal ingredient is a sparingly soluble substance, it can be carried in the fiber in a highly soluble amorphous state, so there is also the advantage that the medicinal ingredient that can be transdermally administered can be widely used.

The content of component (c) in the composition for spraying varies depending on the type of the medicinal ingredient, but is preferably 0.1% by mass or more from the viewpoint of improving efficacy, abrasion resistance, bending resistance, etc. 1% by mass or more is more preferable, and 2% by mass or more is even more preferable. From the viewpoint of the stability of the medicinal ingredient, the content is preferably 30% by mass or less, more preferably 20% by mass or less, and even more preferably 10% by mass or less. The content of component (c) in the composition for spraying is preferably 0.1% by mass or more and 30% by mass or less, more preferably 1% by mass or more and 20% by mass or less, and further 2% by mass or more and 10% by mass or less. preferable.

In addition to components (a), (b), and (c), the composition for spraying includes component (d), which is used to improve the adhesion of the film formed by electrostatic spraying to the skin, at 20°C. It preferably contains a liquid agent containing one or more selected from liquid oils and polyols. By improving the adhesion of the film formed by electrostatic spraying to the skin, the rate of percutaneous absorption of the medicinal ingredients increases, and external forces such as friction with the skin and clothing, etc., and movement of the skin Therefore, it is possible to provide an external medicine whose medicinal ingredients do not disappear from the skin. Component (d) is preferably non-volatile in the liquid state. Component (d) is generally a material that, like the polymer of component (b), is soluble in the volatile material of component (a). Here, the term "dissolved" means that it is in a dispersed state at 20° C. and that the dispersed state is visually uniform, preferably visually transparent or translucent.

As component (d), an oil that is liquid at 20° C., an appropriate one is used depending on the nature of the volatile substance of component (a). Examples of the oil include hydrocarbon oils, ester oils, silicone oils, and higher alcohols that are liquid at 20° C. Liquid oils selected from these can be used singly or in combination of two or more. In the present invention, oil that is liquid at 20°C is also referred to as "liquid oil". Here, ester oils include compounds having an ester structure with an HLB value of 10 or less, in addition to oils such as triglycerides contained in vegetable oils. Here, the HLB value is an index showing the hydrophilic-lipophilic balance (Hydrophile Lipophile Balance), and in the present invention, the value calculated by the following formula by Oda and Teramura et al. HLB = (Σ inorganic value / Σ organic value) × 10
Component (d) preferably contains an oil that is liquid at 20° C. from the viewpoint of further improving the adhesion of the polymer of component (b) to an object to be coated, and has polarity. From the viewpoint of improving the adhesion of the polymer to the object to be coated, it preferably contains one or more selected from ester oils and higher alcohols, and one or two selected from ester oils. It is preferred to contain more than one seed.

Hydrocarbon oils that are liquid at 20°C as the component (d) include liquid paraffin, squalane, squalene, n-octane, n-heptane, cyclohexane, light isoparaffin, liquid isoparaffin, etc., and improve the feeling of use. From the point of view, liquid paraffin and squalane are preferable. From the viewpoint of adhesion of the electrostatically sprayed film to the skin, the viscosity of the hydrocarbon oil at 30° C. is preferably 10 mPa·s or more, more preferably 30 mPa·s or more. From this point of view, the content of isododecane, isohexadecane, and hydrogenated polyisobutene, which have a viscosity of less than 10 mPa·s at 30° C., in the composition for spraying is preferably 10% by mass or less, more preferably 5% by mass or less. , more preferably 1% by mass or less, still more preferably 0.5% by mass or less, and may not be contained. The viscosity here is measured at 30° C. with a BM viscometer (manufactured by Tokimec, measurement conditions: rotor No. 1, 60 rpm, 1 minute).

Examples of the ester oil that is liquid at 20°C as the component (d) include ester compounds having an HLB value of 10 or less, such as fatty acid esters, fatty acid alcohol esters, polyhydric alcohol esters, glycerin fatty acid esters, polyglycerin fatty acid esters, Sorbitan fatty acid esters can be mentioned, and one or more selected from these can be used. Glycerin fatty acid esters include monoglycerin fatty acid esters, diglycerin fatty acid esters, and triglycerin fatty acid esters.

Examples of ester oils that are liquid at 20°C as component (d) include isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, and oleic acid. Decyl, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid ester, monoisostearic acid N-alkyl glycol, neopentyl glycol dicaprate, diisostearyl malate, glyceryl di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythyl tetra-2-ethylhexanoate Slit, glyceryl tri-2-ethylhexanoate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, diethylhexyl naphthalenedicarboxylate, alkyl benzoate (C12-15), cetearyl isononanoate, tri (caprylic/capric) glycerin, (dicaprylic/capric) butylene glycol, glyceryl trilaurate, glyceryl trimyristate, glyceryl tripalmitate, glyceryl triisostearate, glyceryl tri-2-heptylundecanoate , glyceryl tribehenate, glyceryl tricoate, glyceryl trioleate, glyceryl trilinoleate, castor oil fatty acid methyl ester, oleyl oleate, 2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid- 2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, isobutyl adipate, diethyl sebacate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, adipic acid 2-hexyldecyl, diisopropyl sebacate, di-2-ethylhexyl succinate, triethyl citrate, 2-ethylhexyl paramethoxycinnamate, tripropylene glycol dipivalate and the like.

Among them, octyldodecyl myristate, myristyl myristate, isocetyl stearate, isocetyl isostearate, and cetearyl are preferred from the viewpoint of adhesion of the electrostatically sprayed film to the skin and improvement of feel when applied to the skin. isononanoate, isobutyl adipate, diethyl sebacate, di-2-ethylhexyl sebacate, isopropyl myristate, isopropyl palmitate, diisostearyl malate, neopentyl glycol dicaprate, alkyl benzoate (C12-15), At least one selected from tri(caprylic/capric)glycerin and triglycerides such as glyceryl trioleate, glyceryl tristearate, and glyceryl tripalmitate is preferable, and isopropyl myristate, isopropyl palmitate, and diisostearyl malate. , diethyl sebacate, neopentyl glycol dicaprate, alkyl benzoate (C12-15), tri(caprylic/capric)glycerol, and triglyceride.

In addition, vegetable oils such as olive oil, jojoba oil, macadamia nut oil, medform oil, castor oil, safflower oil, sunflower oil, avocado oil, canola oil, Chinese ginseng oil, rice germ oil, and rice bran oil containing ester oils such as triglycerides described above Animal oils, including lanolin, etc., can also be used.

The polyglycerin fatty acid ester contained in the ester oil that is liquid at 20° C. as the component (d) includes polyglyceryl isostearate, polyglyceryl diisostearate, polyglyceryl triisostearate, polyglyceryl stearate, which have an HLB value of 10 or less, Polyglyceryl oleate, polyglyceryl sesquicaprate. As sorbitan fatty acid esters, sorbitan monostearate, sorbitan monooleate, sorbitan sesquioleate, sorbitan sesquiisostearate, sorbitan monopalmitate, sorbitan tristearate, and sorbitan trioleate having an HLB value of 10 or less. , coconut oil fatty acid sorbitan, and the like.
Among them, polyglyceryl isostearate, polyglyceryl diisostearate, polyglyceryl triisostearate, polyglyceryl stearate, oleic acid, from the viewpoint of adhesion of the electrostatically sprayed film to the skin and improvement of the feeling when applied to the skin. Polyglyceryl and polyglyceryl sesquicaprate are preferred, and polyglyceryl diisostearate is more preferred.

Examples of silicone oils that are liquid at 20° C. as component (d) include dimethylpolysiloxane, dimethylcyclopolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, and higher alcohol-modified organopolysiloxane. In the composition for spraying of the present invention, the content of silicone oil in the composition for spraying is preferably 10% by mass or less, more preferably 5% by mass or less, from the viewpoint of improving adhesion to the skin or the like. , more preferably 1% by mass or less, and even more preferably 0.1% by mass or less.
The kinematic viscosity of the silicone oil at 25° C. is preferably 3 mm ² /s or more, more preferably 4 mm ² /s or more, still more preferably 5 mm, from the viewpoint of adhesion of the electrostatically sprayed film to the skin or the like. ² /s or more, preferably 30 mm ² /s or less, more preferably 20 mm ² /s or less, still more preferably 10 mm ² /s or less. Among these, the silicone oil preferably contains dimethylpolysiloxane from the viewpoint of adhesion of the electrostatically sprayed film.

Examples of the higher alcohols that are liquid at 20° C. as component (d) include liquid higher alcohols having 12 to 20 carbon atoms, preferably higher alcohols of branched fatty acids or unsaturated fatty acids, such as isostearyl alcohol and oleyl alcohol. more preferred.

Also, when component (d) is a polyol, an appropriate one is used depending on the nature of the volatile substance of component (a). Specifically, the polyol includes alkylene glycol such as ethylene glycol, propylene glycol, 1,3-propanediol, and 1,3-butanediol; diethylene glycol, dipropylene glycol, polyethylene glycol having a number average molecular weight of 1000 or less, and polypropylene. polyalkylene glycols such as glycols; glycerines or polyglyceryls such as glycerin, diglycerin, triglycerin; Among these, ethylene glycol, propylene glycol, 1,3-butanediol, dipropylene glycol, polyethylene glycol, glycerin and diglycerin are preferred from the viewpoint of improving the feeling of use, and propylene glycol, 1,3-butanediol and glycerin are preferred. is more preferred. The number average molecular weight of polyethylene glycol is more preferably 600 or less, more preferably 400 or less.

The oils and polyols liquid at 20° C. mentioned above as examples of component (d) can be used alone or in combination of two or more. Component (d) is preferably a plasticizer for a film-forming polymer. As described above, component (d) is an oil that is liquid at 20°C selected from hydrocarbon oils, ester oils, silicone oils, and higher alcohols, and a polyol selected from alkylene glycol, polyalkylene glycol, glycerin and triglycerin. It is preferably one or two or more substances selected from.

The content of component (d) in the composition for spraying is preferably 0.5% by mass or more, more preferably 1.0% by mass or more, and 1.5% by mass or more. is more preferred. The content is preferably 30% by mass or less, more preferably 25% by mass or less, and even more preferably 20% by mass or less. The content of component (c) in the composition for spraying is preferably 0.5% by mass or more and 30% by mass or less, more preferably 1% by mass or more and 25% by mass or less, and 1.5% by mass. It is more preferable that the content is 20% by mass or more. By blending the component (d) in the composition for spraying in this proportion, the adhesion of the intended coating to the coating-forming object can be improved.

The composition for spraying in the present invention may contain solid or semi-solid oil, that is, oil other than component (d), as long as the effects of the present invention are not impaired. From the viewpoint of improving the adhesion of the film to the skin and from the viewpoint of the stability of the composition for spraying, the amount of oil other than component (d) in the composition for spraying is preferably 10% by mass or less. , is more preferably 8% by mass or less, and even more preferably 6% by mass or less.

The spray composition may contain only component (a), component (b) and component (c) described above, or may contain component (a), component (b) and component (c) in addition to component (a), component (b) and component (c). It may contain component (d) and other components. Other components include, for example, solvent, color pigment, extender, dye, surfactant with HLB value exceeding 10, UV protection agent, fragrance, repellent, oxidation Inhibitors, stabilizers, preservatives, antiperspirants, various vitamins and the like are included. In addition, each of these agents is not limited to the use as each agent, and other uses such as antiperspirants can be used as fragrances depending on the purpose. Alternatively, it can be used in combination with other uses, for example, as an antiperspirant and perfume. When other components are contained in the composition for spraying, the mixing ratio of the other components is preferably 0.1% by mass or more and 30% by mass or less, and 0.5% by mass or more and 20% by mass or less. It is even more preferable to have

In the present invention, the composition for spraying is used by electrostatically spraying directly onto the skin to form a film on the skin.

When electrostatic spraying is performed, a spraying composition having a viscosity at 25° C. of preferably 1 mPa·s or more, more preferably 10 mPa·s or more, and still more preferably 50 mPa·s or more is used. Also, the viscosity at 25° C. is preferably 5000 mPa·s or less, more preferably 2000 mPa·s or less, still more preferably 1500 mPa·s or less. The viscosity of the spray composition at 25° C. is preferably 1 mPa·s or more and 5000 mPa·s or less, more preferably 10 mPa·s or more and 2000 mPa·s or less, and still more preferably 50 mPa·s or more and 1500 mPa·s or less. is. A spray composition having a viscosity in this range can be used to successfully form a coating, particularly a porous coating consisting of a deposit of fibers, by electrostatic spraying. The formation of a porous film is advantageous from the viewpoint of improving the prevention of stuffiness of the skin, etc., improving the percutaneous absorption of medicinal ingredients, improving the adhesion of the film to the skin, improving the durability of the film, and the like. be. The viscosity of the composition for spraying is measured at 25° C. using an E-type viscometer. As the E-type viscometer, for example, an E-type viscometer manufactured by Tokyo Keiki Co., Ltd. can be used. As the rotor in that case, rotor No. 43 can be used.

The spray composition is directly sprayed onto human skin by electrostatic spraying. The electrostatic spraying method includes a step of electrostatically spraying a composition for spraying onto the skin using an electrostatic spraying device in the electrostatic spraying step to form a film. The electrostatic spray device includes a container containing a composition for spraying, a nozzle for discharging the composition for spraying, a supply device for supplying the composition for spraying contained in the container to the nozzle, and a voltage applied to the nozzle. and a power supply for applying Preferably, FIG. 1 shows a schematic representation of the configuration of an electrostatic spray device that is preferably used in the present invention. The electrostatic spray device 10 shown in FIG. 1 includes a low voltage power supply 11 . The low-voltage power supply 11 can generate a voltage of several volts to ten and several volts. In order to increase the portability of the electrostatic spray device 10, the low voltage power supply 11 preferably consists of one or more batteries. Also, by using a battery as the low-voltage power supply 11, there is an advantage that it can be easily replaced as necessary. An AC adapter or the like can be used as the low-voltage power supply 11 instead of the battery.

Electrostatic spray device 10 also includes a high voltage power supply 12 . The high voltage power supply 12 is connected to the low voltage power supply 11 and has an electronic circuit (not shown) that boosts the voltage generated by the low voltage power supply 11 to a high voltage. The boost electronic circuit is generally composed of transformers, capacitors, semiconductor devices, and the like.

Electrostatic spray device 10 further comprises an auxiliary electrical circuit 13 . The auxiliary electric circuit 13 is interposed between the low-voltage power supply 11 and the high-voltage power supply 12 described above, and has a function of adjusting the voltage of the low-voltage power supply 11 to stably operate the high-voltage power supply 12 . Furthermore, the auxiliary electric circuit 13 has a function of controlling the number of revolutions of a motor provided in a micro gear pump 14, which will be described later. By controlling the number of revolutions of the motor, the supply amount of the spray composition from the spray composition container 15 to the micro gear pump 14, which will be described later, is controlled. A switch SW is attached between the auxiliary electric circuit 13 and the low-voltage power supply 11, and the electrostatic spray device 10 can be operated/stopped by turning on/off the switch SW.

Electrostatic spray device 10 further comprises nozzle 16 . The nozzle 16 is made of various conductors such as metals, or non-conductors such as plastics, rubbers and ceramics, and has a shape that allows the composition for spraying to be discharged from its tip. A minute space through which the composition for spraying flows is formed in the nozzle 16 along the longitudinal direction of the nozzle 16 . The size of the cross section of this minute space is preferably 100 μm or more and 1000 μm or less in terms of diameter. Nozzle 16 communicates with micro gear pump 14 via conduit 17 . Conduits 17 may be conductive or non-conductive. Also, the nozzle 16 is electrically connected to the high voltage power supply 12 . This makes it possible to apply a high voltage to the nozzle 16 . In this case, the nozzle 16 and the high-voltage power supply 12 are electrically connected via a current limiting resistor 19 in order to prevent excessive current from flowing when the human body directly touches the nozzle 16 .

A micro gear pump 14 communicating with the nozzle 16 via a conduit 17 functions as a supply device for supplying the spray composition contained in the container 15 to the nozzle 16 . The micro gear pump 14 operates by receiving power from the low voltage power supply 11 . The micro gear pump 14 is also configured to supply a predetermined amount of the spray composition to the nozzle 16 under the control of the auxiliary electrical circuit 13 .

A container 15 is connected to the micro gear pump 14 via a flexible conduit 18 . The container 15 contains the spray composition. Container 15 is preferably in the form of a replaceable cartridge.

The electrostatic spray device 10 having the above configuration can be used, for example, as shown in FIG. FIG. 2 shows a handheld electrostatic spray device 10 having dimensions that allow it to be held with one hand. In the electrostatic spray device 10 shown in the figure, all the members shown in the configuration diagram shown in FIG. A nozzle (not shown) is arranged at one end 10a of the housing 20 in the longitudinal direction. The nozzle is arranged in the housing 20 so that the blowing direction of the composition coincides with the longitudinal direction of the housing 20, and the nozzle protrudes toward the skin side of the film-forming object. Since the tip of the nozzle is arranged in a convex shape toward the film formation object in the longitudinal direction of the housing 20, the composition for spraying is less likely to adhere to the housing, and the film is stably formed. be able to.

When the skin to be coated is the user's own skin, when the electrostatic spray device 10 is operated, the user, that is, the person who forms the coating on the skin by the electrostatic spray, holds the device 10 by hand. Then, one end 10a of the device 10, where the nozzle (not shown) is located, is aimed at the target area to be electrostatically sprayed. In FIG. 2, one end 10a of the electrostatic spray device 10 is shown directed toward the inside of the forearm of the user. Under this condition, the device 10 is switched on to perform the electrostatic spray method. Turning on the device 10 creates an electric field between the nozzle and the skin. In the embodiment shown in FIG. 2, a high positive voltage is applied to the nozzle and the skin is the negative electrode. When an electric field is generated between the nozzle and the skin, the composition for spraying at the tip of the nozzle is polarized by electrostatic induction, and the tip portion becomes cone-shaped, and droplets of the composition for spraying are charged from the tip of the cone. is ejected into the air along the electric field toward the skin. When component (a), which is a solvent, evaporates from the charged composition for spraying discharged into space, the charge density on the surface of the composition for spraying becomes excessive, and spreads in space while being repeatedly finely divided by Coulombic repulsive force. , reaches the skin. In this case, by appropriately adjusting the viscosity of the spray composition, the sprayed composition can reach the skin in the form of droplets. Alternatively, while being discharged into the space, the volatile substance component (a), which is a solvent, is volatilized from the composition, and the polymer having film-forming ability, which is a solute, is solidified while being stretched and deformed by a potential difference. It is also possible to form fibers and deposit the fibers on the surface of the skin. For example, increasing the viscosity of the composition for spraying tends to deposit the composition on the surface of the skin in the form of fibers. This forms a coating of fibrous deposits on the surface of the skin. A coating composed of a deposit of fibers can also be formed by adjusting the distance between the nozzle and the skin and the voltage applied to the nozzle.

During the electrostatic spray method, a high potential difference is generated between the skin, which is the object to be coated, and the nozzle. However, since the impedance is very large, the current flowing through the human body is extremely small. The inventors have confirmed that the current flowing through the human body during electrostatic spraying is several orders of magnitude smaller than the current flowing through the human body due to, for example, static electricity generated in normal life.

When the fiber deposit is formed by an electrostatic spray method, the thickness of the fiber is preferably 10 nm or more, more preferably 50 nm or more, in terms of equivalent circle diameter. Also, it is preferably 3000 nm or less, more preferably 1000 nm or less. For the thickness of the fiber, for example, by scanning electron microscope (SEM) observation, the fiber is magnified 10,000 times and observed, and defects (fiber clumps, fiber intersections, droplets) are removed from the two-dimensional image, Ten fibers are arbitrarily selected, a line perpendicular to the longitudinal direction of the fibers is drawn, and the fiber diameter can be directly read.

The film, which is a deposit of fibers formed by an electrostatic spray method, has a medicinal component-carrying film in which component (c) or component (c) and component (d) are present on the surface side of the constituent fibers. ing. The surface side of the fiber means the surface, part of the surface, or between the fibers. The content of component (c), or component (c) and component (d), in the spray composition also depends on the affinity of the polymer with component (c), or component (c) and component (d). However, if it is approximately 1% by mass or more, the constituent fibers swell and become soft, and the conformability to the skin increases. A medicinal ingredient-carrying film is easily formed between them, and on the other hand, if the content of component (c) or component (c) and component (d) in the composition for spraying is less than 1% by mass, the constituent fibers It is difficult to form the liquid agent-carrying film on the surface of the When the medicinal ingredient-carrying coating is formed on the fibers constituting the coating in this way, the adhesiveness to the skin, which is the object of coating formation, is enhanced, and the coating tends to become transparent, giving it a more natural appearance. Furthermore, since the durability of adhesion increases, an effect of improving the percutaneous absorbability of the medicinal ingredient can be obtained.

When the film-forming object is skin containing sweat, sebum, etc., the component (c) or the component (c) and the component (d) are combined in the fiber, thereby swelling the fiber and facilitating plasticization. For example, when the same composition is electrostatically sprayed for 5 seconds on a metal surface that does not contain water or oil and a skin surface that contains water or oil, such as the palm of the hand, changes in fiber diameter are observed over time. Then, the fibers electrostatically sprayed on the skin surface become larger in diameter over time due to swelling than the fibers electrostatically sprayed on the metal surface. In this way, the film containing fibers formed by electrostatic spraying is plasticized by the oil and moisture in the skin and becomes even softer, so that the fibers themselves improve the followability to the texture of the skin, and the fibers themselves are improved. The component (c), or the component (c) and the component (d) bleed out from the fiber surface and between the fibers, so that the coating containing the fibers becomes translucent or transparent, and the natural appearance Saga is given. When the film formation target is skin containing sweat, sebum, or the like, the fiber diameter due to swelling satisfies the following formula (1).
(Fiber diameter after 30 seconds after spinning on skin)>(Fiber diameter after 30 seconds after spinning on metal plate) (1)

A medicinal ingredient with high crystallinity generally has low solubility in water and is often poor in percutaneous absorbability. In the present invention, the component (c) in the film, which is a deposit of fibers formed from the spray composition by the electrostatic spray method, is derived from the extremely high drying rate peculiar to the electrostatic spray method. Even highly crystalline medicinal ingredients can be supported in the film in an amorphous state. From this, it is considered that even if the medicinal ingredient is highly crystalline, the effect of improving the percutaneous absorbability of the medicinal ingredient (c) can be obtained.

The mass ratio ((c)/(b)) of the component (c) to the component (b) in the coating or the composition for spraying, which is a deposit of fibers formed by an electrostatic spray method, is the adhesion of the coating. From the viewpoint of improving durability, it is preferably 0.01 or more, more preferably 0.1 or more, and still more preferably 0.6 or more, and from the viewpoint of improving percutaneous absorption rate, preferably 20. or less, more preferably 10 or less, still more preferably 6 or less, and even more preferably 4.5 or less. From a similar point of view, the mass ratio ((c)/(b)) in the coating or spray composition is preferably 0.01 or more and 20 or less, more preferably 0.1 or more and 10 or less. It is more preferably 0.6 or more and 6 or less, and even more preferably 0.6 or more and 4.5 or less. If the value of ((c)/(b)) is within the above range, the fiber is easily formed, the coating is excellent in adhesion and durability, and the poorly soluble medicinal ingredient is retained in the fiber in an amorphous state. Therefore, the percutaneous absorption rate is improved.

The value of the mass ratio ((d)/(b)) of component (d) to component (b) in a coating or spray composition that is a deposit of fibers formed by an electrostatic spray method is the adhesion of the coating. From the viewpoint of improving the properties and durability, it is preferably 0.01 or more, more preferably 0.05 or more, and still more preferably 0.1 or more, and from the viewpoint of ease of forming a fibrous coating. , preferably 10 or less, more preferably 5 or less, still more preferably 4 or less. From a similar point of view, the mass ratio ((d)/(b)) of component (d) to component (b) in the coating or spray composition is preferably 0.01 or more and 10 or less. It is more preferably 0.05 or more and 5 or less, and even more preferably 0.1 or more and 4 or less. If the value of ((d)/(b)) is within the above range, the fiber is easily formed, the coating is excellent in adhesion and durability, and the poorly soluble medicinal ingredient is retained in the fiber in an amorphous state. Therefore, the percutaneous absorption rate is improved.

The contents of component (a), component (b), component (c) and component (d) in the composition for spraying are measured as follows. Component (a), which is a volatile substance, does not exist in the formed film, or volatilizes even if it exists, so only component (b), component (c) and component (d) are present in the formed film. It is measured in the state in which it is contained, and the content is measured as follows.

<Method for measuring the content of component (a), component (b), component (c) and component (d) in spray composition>
There is a method of separation and identification by liquid chromatography (HPLC) in a solution state, and a method of identification by an infrared spectrophotometer (IR). In liquid chromatography, components with higher molecular weights are eluted first, so the composition can be identified by predicting the molecular weight and the elution position of the components. In IR analysis, it is also possible to assign and identify functional groups from individual absorbers, and in general, it is possible to identify by comparing the standard chart of commercially available additives and the IR chart of the component.

<Method for measuring the identified content of component (b), component (c) and component (d) in the formed coating>
A solvent capable of dissolving the film is searched for, and after dissolving the film in the solvent, separation and identification by liquid chromatography (HPLC) or identification by infrared spectrophotometer (IR) are performed.

In principle, the fibers forming the coating are continuous fibers of infinite length, but preferably have a length of at least 100 times the thickness of the fibers. In this specification, a fiber having a length of 100 times or more the thickness of the fiber is defined as "continuous fiber". The coating produced by the electrostatic spray method is preferably a porous, discontinuous coating composed of deposits of continuous fibers. The film in this form can not only be handled as a single sheet as an aggregate, but also has the characteristic of being extremely soft. It has the advantage of being superior. Another advantage is that the coating can be completely removed easily. On the other hand, a continuous film having no pores is not easily peeled off, and has low perspiration wicking properties, so that the skin may become stuffy. In addition, a porous discontinuous film consisting of an aggregate of particles requires an operation such as rubbing the entire film in order to completely remove the film, and it is difficult to completely remove it without damaging the skin. Have difficulty.

In the electrostatic spraying process using the electrostatic spraying device 10, the composition for spraying that has been electrostatically sprayed and fibrous is charged with the component (b) and the component (c) while the component (a) evaporates. reach the skin directly. As mentioned above, the skin is also charged, so the fibers adhere to the skin in the form of a sheet of film due to electrostatic force. Since fine irregularities such as texture are formed on the surface of the skin, the fibers adhere more firmly to the surface of the skin in the form of a sheet of film in combination with the anchoring effect of the irregularities. After electrostatic spraying is completed in this manner, the electrostatic spray device 10 is turned off. As a result, the electric field between the nozzle and the skin disappears and the charge is fixed on the surface of the skin. As a result, the adhesiveness of the coating in the form of a single sheet is further exhibited, the coating is less likely to peel off from the edges during wear, and the durability during use is improved. Moreover, since the fibers constituting the coating contain the component (c), the coating can be sufficiently adhered to the skin without applying a separate liquid to the skin. The reason for this is that the presence of component (c) in the fiber softens the fiber itself due to the plasticizing effect and enhances conformability to fine uneven surfaces, and component (c) bleeds out to the fiber surface. This is thought to be due to the fact that liquid bridges are formed between the fibers and the skin. Furthermore, since it has a medicinal ingredient-carrying coating in which the component (c) is present between the fibers constituting the coating or on the surface of the fiber, the fibers constituting the coating hardly reflect light, and the coating is transparent in appearance. It is easy to become, and the skin can be covered with a natural appearance.

Although the distance between the nozzle and the skin depends on the voltage applied to the nozzle, it is preferably 50 mm or more and 150 mm or less for successful formation of the coating. The distance between the nozzle and the skin can be measured with a commonly used non-contact sensor or the like.

Regardless of whether the coating formed by the electrostatic spray method is porous or not, the basis weight of the coating is preferably 0.1 g/m ² or more, and is 1 g/m ² or more. is more preferred. It is also preferably 50 g/m ² or less, more preferably 40 g/m ² or less. For example, the basis weight of the coating is preferably 0.1 g/m ² or more and 50 g/m ² or less, more preferably 1 g/m ² or more and 40 g/m ² or less. By setting the basis weight of the coating in this manner, the adhesion of the coating can be improved.

The electrostatic spraying step of directly electrostatically spraying the composition onto the skin to form a film means a step of electrostatically spraying the composition onto the skin to form a film. The step of electrostatically spraying the composition onto a place other than the skin to prepare a sheet-like material and attaching the sheet to the skin to form a film is different from the electrostatic spraying step.

Although the present invention has been described above based on its preferred embodiments, the present invention is not limited to the above embodiments. For example, in the above embodiment, a person wishing to coat their skin held the electrostatic spray device 10 and created an electric field between the nozzle of the device 10 and their skin. Electrostatic spray device 10 does not need to be held by a person wishing to coat their skin as long as an electric field is generated in the device.

The present invention further discloses the following topical medicines in relation to the above-described embodiments.
<1> A topical preparation containing component (a), component (b) and component (c), wherein the composition containing component (a), component (b) and component (c) is directly applied to the skin. An external medicine characterized by being used by electrospraying to form a film on the skin.
(a) one or more volatile substances selected from water, alcohols and ketones;
(b) a polymer with film-forming ability;
(c) A medicinal ingredient that can be transdermally administered.

<2> The topical medicine according to <1>, which is electrostatically sprayed directly onto the skin to form a film of fiber deposits on the skin.
<3> The step of electrostatically spraying is a step of electrostatically spraying the composition onto the skin using an electrostatic sprayer to form a film made of fiber deposits,
The electrostatic spray device comprises a container containing the composition, a nozzle for discharging the composition, a supply device for supplying the composition contained in the container to the nozzle, and a voltage applied to the nozzle. The topical medicine according to <1> or <2>, further comprising a power supply that applies the

<4> The volatile substance of component (a) has a vapor pressure of 0.01 kPa or more and 106.66 kPa or less, preferably 0.13 kPa or more and 66.66 kPa or less, more preferably 0.01 kPa or more and 106.66 kPa or less at 20°C. The topical preparation according to any one of <1> to <3> above, which is 67 kPa or more and 40.00 kPa or less, more preferably 1.33 kPa or more and 40.00 kPa or less.
<5> Among the volatile substances of the component (a), as the alcohol, a monovalent chain aliphatic alcohol, a monovalent cycloaliphatic alcohol, or a monovalent aromatic alcohol is used. As, ethanol, isopropyl alcohol, butyl alcohol, phenylethyl alcohol, propanol, pentanol, etc. are used, and these alcohols use one or more selected from these, <1> to <4> The topical drug according to any one of the above.
<6> Among the volatile substances of component (a), acetone, methyl ethyl ketone, methyl isobutyl ketone, etc. are used as ketones, and these ketones are used alone or in combination of two or more. The topical medicine according to any one of <1> to <5>.
<7> The volatile substance of component (a) is one or more selected from ethanol, isopropyl alcohol, butyl alcohol and water, preferably one or two selected from ethanol and butyl alcohol. The topical medicine according to any one of the above <1> to <6>, which is at least one seed, and is most preferably ethanol.

<8> The polymer having film-forming ability is water-soluble,
The water-soluble polymer having film-forming ability includes pullulan, hyaluronic acid, chondroitin sulfate, poly-γ-glutamic acid, modified corn starch, β-glucan, glucooligosaccharide, heparin, mucopolysaccharides such as keratosulfate, cellulose, pectin, Xylan, lignin, glucomannan, galacturonic acid, psyllium seed gum, tamarind seed gum, gum arabic, tragacanth gum, soybean water-soluble polysaccharide, alginic acid, carrageenan, laminaran, agarose, fucoidan, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose natural polymers, partially saponified polyvinyl alcohol (when not used in combination with a cross-linking agent), low saponified polyvinyl alcohol, polyvinylpyrrolidone (PVP), polyethylene oxide, synthetic polymers such as sodium polyacrylate, and these water-soluble polymers The topical medicine according to any one of <1> to <7>, which is used alone or in combination of two or more.
<9> The polymer having film-forming ability is water-insoluble,
The water-insoluble polymer capable of forming a film includes fully saponified polyvinyl alcohol that can be insolubilized after film formation, partially saponified polyvinyl alcohol that can be crosslinked after film formation by using a crosslinking agent, and poly(N-propanoylethyleneimine). ) Oxazoline-modified silicone such as graft-dimethylsiloxane/γ-aminopropylmethylsiloxane copolymer, polyvinylacetal diethylaminoacetate, twein (main component of corn protein), polyester, polylactic acid (PLA), polyacrylonitrile resin, polymethacrylic acid Resins such as acrylic resins, polystyrene resins, polyvinyl butyral resins, polyethylene terephthalate resins, polybutylene terephthalate resins, polyurethane resins, polyamide resins, polyimide resins, polyamideimide resins, and these water-insoluble polymers may be used alone or in combination of two or more. The topical medicine according to any one of <1> to <7>, which is used in combination.
<10> Component (c) is α-adrenergic receptor blocker, adrenergic receptor stimulant, angiotensin II receptor antagonist, angiotensin-converting enzyme inhibitor, calcium antagonist, steroidal anti-inflammatory/anti-inflammatory analgesic, Parkinson's disease Therapeutic drugs, vitamin-related drugs, hormone drugs, drugs for athlete's foot and tinea (antifungal drugs), antipyretic analgesics, drugs for external hemorrhoids, coronary vasodilators, bronchodilators and antitussives, cardiotonic drugs, antianginal drugs, Local anesthetics, hypoglycemic drugs, oropharyngeal drugs, psychotropic drugs, antiallergic drugs, antihistamines, antibacterial drugs, antiparasitic/anthelmintic/insecticide drugs, antiarrhythmic drugs, antiemetic drugs, antihyperlipidemic drugs, Bactericidal drug, hemostatic drug, medicine for women, antiseptic drug, sleeping drug, tissue respiration activator, antipruritic anti-inflammatory drug, isotonic solution, skin disease therapeutic agent, non-steroidal anti-inflammatory/anti-inflammatory analgesic, moisturizing agent, erectile dysfunction drug , an anesthetic, a peripheral vasodilator, an immunosuppressant, a hair drug, a diuretic, an enema and a smoking cessation aid, preferably an adrenergic receptor stimulant, a steroidal anti-inflammatory/anti-inflammatory Analgesics, vitamin-related drugs, external hemorrhoid drugs, bronchodilators/antitussives, oropharyngeal drugs, psychotropic drugs, antiallergic drugs, antihistamines, antibacterial drugs, antiparasitic/anthelmintic/insecticides, bactericidal drugs, hemostatic drugs, At least one selected from female drugs, antiseptics, tissue respiration activators, antipruritic antiphlogistic agents, isotonic solutions, therapeutic agents for skin diseases, non-steroidal anti-inflammatory/anti-inflammatory analgesics, moisturizing agents, immunosuppressive agents and hair preparations The topical medicine according to any one of <1> to <9>, which is a seed.
<11> Component (c) is preferably a non-steroidal anti-inflammatory/anti-inflammatory analgesic, more preferably one or more selected from felbinac, diclofenac or salts thereof, loxoprofen and flurbiprofen. The topical medicine according to any one of <1> to <10>.
<12> The content of component (a) in the composition is 50% by mass or more, preferably 55% by mass or more, more preferably 60% by mass or more, and 98% by mass or less, preferably 96% by mass. Below, more preferably 94% by mass or less, 50% by mass or more and 98% by mass or less, preferably 55% by mass or more and 96% by mass or less, further preferably 60% by mass or more and 94% by mass or less, the <1> The topical medicine according to any one of <11>.
<13> The content of component (b) in the composition is 2% by mass or more, preferably 4% by mass or more, more preferably 6% by mass or more, and 50% by mass or less, preferably 45% by mass. Below, more preferably 40% by mass or less, 2% by mass or more and 50% by mass or less, preferably 4% by mass or more and 45% by mass or less, further preferably 6% by mass or more and 40% by mass or less, <1> The topical medicine according to any one of <12>.

<14> The content of the component (c) in the composition is 0.5% by mass or more, preferably 1.0% by mass or more, more preferably 1.5% by mass or more, and 30% by mass or less, Preferably 25% by mass or less, more preferably 20% by mass or less, 0.5% by mass or more and 30% by mass or less, preferably 1% by mass or more and 25% by mass or less, more preferably 1.5% by mass or more and 20% by mass % or less, the topical medicine according to any one of <1> to <13>.
<15> The composition has a viscosity of 1 mPa·s or more, preferably 10 mPa·s or more, more preferably 50 mPa·s or more at 25°C, and preferably 5000 mPa·s or less at 25°C. is 2000 mPa s or less, more preferably 1500 mPa s or less, 1 mPa s or more and 5000 mPa s or less, preferably 10 mPa s or more and 2000 mPa s or less, more preferably 50 mPa s or more and 1500 mPa s or less, The topical medicine according to any one of <1> to <14>.
<16> The topical medicine according to any one of <1> to <15>, wherein the composition further contains component (d) one or more selected from oils and polyols that are liquid at 20°C.
<17> The coating has a medicinal component-carrying coating in which the component (c) or the component (c) and the component (d) are present on the surface side of the constituent fibers, the <1> to <16> The topical medicine according to any one of above.
<18> The mass ratio ((c)/(b)) of component (b) to component (c) in the coating or spray composition is 0.01 or more and 20 or less, preferably 0.01 or more and 20 or less. The topical medicine according to any one of the above <1> to <17>, which is 1 or more and 10 or less, more preferably 0.6 or more and 6 or less, and still more preferably 0.6 or more and 4.5 or less.
<19> The mass ratio ((d)/(b)) of the component (b) to the component (d) in the film or spray composition is 0.01 or more and 10 or less, preferably 0.01 or more and 10 or less. 05 or more and 5 or less, more preferably 0.1 or more and 4 or less, the topical medicine according to any one of the above <1> to <18>.
<20> Any of the above <16> to <19>, wherein the component (d) is one or more substances selected from hydrocarbon oils, ester oils, silicone oils, higher alcohols, and polyols. The topical drug described in Crab.
<21> The oil that is liquid at 20°C, which is the component (d), is a hydrocarbon oil, an ester oil, a silicone oil, or a higher alcohol that is liquid at 20°C, and one or two liquid oils selected from these are used in combination with
The ester oil includes a compound having an ester structure with an HLB value of 10 or less in addition to oils such as triglycerides contained in vegetable oils,
The oil that is liquid at 20°C, which is the component (c), preferably contains one or more selected from ester oils and higher alcohols, more preferably one or more selected from ester oils. The topical medicine according to any one of <16> to <20>, containing
<22> The component (d), a hydrocarbon oil liquid at 20°C, is liquid paraffin, squalane, squalene, n-octane, n-heptane, cyclohexane, light isoparaffin, liquid isoparaffin, preferably liquid paraffin, The topical medicine according to <21>, which is squalane.
<23> The topical medicine according to <21> or <22>, wherein the hydrocarbon oil has a viscosity at 30°C of 10 mPa·s or more, preferably 30 mPa·s or more.

<24> The content of isododecane, isohexadecane, and hydrogenated polyisobutene having a viscosity of less than 10 mPa s at 30°C in the composition is 10% by mass or less, preferably 5% by mass or less, and more preferably 1% by mass. %, more preferably 0.5% by mass or less, or the composition does not contain isododecane, isohexadecane, hydrogenated polyisobutene, which has a viscosity of less than 10 mPa s at 30° C., said <22 > or the topical medicine according to <23>.
<25> The ester oil that is liquid at 20°C, which is the component (d), is an ester compound having an HLB value of 10 or less, and is a fatty acid ester, a fatty acid alcohol ester, a polyhydric alcohol ester, a glycerin fatty acid ester, or a polyglycerin fatty acid ester. , sorbitan fatty acid ester, and the topical medicine according to <20> or <21>, wherein one or more selected from these are used.
<26> The ester oil that is liquid at 20°C as the component (d) includes isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, and oleic acid. Decyl, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid ester, monoisostearic acid N-alkyl glycol, neopentyl glycol dicaprate, diisostearyl malate, glyceryl di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythyl tetra-2-ethylhexanoate Slit, glyceryl tri-2-ethylhexanoate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, diethylhexyl naphthalene dicarboxylate, alkyl benzoate (C12-15), cetearyl isono Nanoate, tri (caprylic/capric) glycerin, (dicaprylic/capric) butylene glycol, glyceryl trilaurate, glyceryl trimyristate, glyceryl tripalmitate, glyceryl triisostearate, glyceryl tri-2-heptylundecanoate, Glyceryl tribehenate, glyceryl tricoate, glyceryl trioleate, glyceryl trilinoleate, castor oil fatty acid methyl ester, oleyl oleate, 2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid-2 -octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, isobutyl adipate, diethyl sebacate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-adipate The above <20>, <21> or <25>, which is hexyldecyl, diisopropyl sebacate, di-2-ethylhexyl succinate, triethyl citrate, 2-ethylhexyl paramethoxycinnamate, or tripropylene glycol dipivalate. External medicine.
<27> The above component (d) ester oil liquid at 20°C includes octyldodecyl myristate, myristyl myristate, isocetyl stearate, isocetyl isostearate, cetearyl isononanoate, isobutyl adipate, diethyl sebacate, Di-2-ethylhexyl sebacate, isopropyl myristate, isopropyl palmitate, diisostearyl malate, neopentyl glycol dicaprate, alkyl benzoate (C12-15), tri(caprylic/capric) glycerin, and trio At least one selected from triglycerides such as glyceryl lactate, glyceryl tristearate, and glyceryl tripalmitate is preferable, and isopropyl myristate, isopropyl palmitate, diisostearyl malate, diethyl sebacate, neopentyl glycol dicaprate, and benzoin. <20>, <21>, <25> or <26>, which is one or more selected from alkyl acid (12 to 15 carbon atoms), tri(caprylic/capric)glycerol, and triglyceride The topical drug described in .
<28> The ester oil that is liquid at 20°C, which is the component (d), is a polyglycerin fatty acid ester,
The above <21>, wherein the polyglycerin fatty acid ester is polyglyceryl isostearate, polyglyceryl diisostearate, polyglyceryl triisostearate, polyglyceryl stearate, polyglyceryl oleate, or polyglyceryl sesquicaprate having an HLB value of 10 or less. External medicine.

<29> The ester oil that is liquid at 20°C as the component (d) is a sorbitan fatty acid ester, and the sorbitan fatty acid ester has an HLB value of 10 or less, sorbitan monostearate, sorbitan monooleate, and sesquiolein. The external preparation according to <21>, which is sorbitan acid, sorbitan sesquiisostearate, sorbitan monopalmitate, sorbitan tristearate, sorbitan trioleate, and sorbitan coconut oil fatty acid.
<30> The ester oil that is liquid at 20°C, which is component (d), is polyglyceryl isostearate, polyglyceryl diisostearate, polyglyceryl triisostearate, polyglyceryl stearate, polyglyceryl oleate, and polyglyceryl sesquicaprate, preferably diisostearin. The topical medicine according to <21>, which is a polyglyceryl acid.
<31> The silicone oil that is liquid at 20°C, which is component (d), is dimethylpolysiloxane, dimethylcyclopolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, or higher alcohol-modified organopolysiloxane. 21> external medicine.
<32> The content of the silicone oil in the composition is 10% by mass or less, preferably 5% by mass or less, more preferably 1% by mass or less, and even more preferably 0.1% by mass or less,
The kinematic viscosity of the silicone oil at 25° C. is 3 mm ² /s or more, preferably 4 mm ^{2 /s or more, more preferably 5 mm 2 /} s or more, and 30 mm ² /s or less, preferably 20 mm ² /s or less, more preferably 10 mm ² /s or less,
The topical medicine according to <20>, <21>, and <31>, wherein the silicone oil contains dimethylpolysiloxane.
<33> The higher alcohol liquid at 20°C, which is the component (d), is a liquid higher alcohol having 12 to 20 carbon atoms,
The topical medicine according to <20> or <21> above, wherein the higher alcohol is a higher alcohol of branched fatty acid or unsaturated fatty acid, preferably isostearyl alcohol or oleyl alcohol.

<34> The component (d) is a polyol,
The polyols include alkylene glycols such as ethylene glycol, propylene glycol, 1,3-propanediol and 1,3-butanediol; Glycol; glycerin or polyglyceryl such as glycerin, diglycerin, triglycerin, preferably ethylene glycol, propylene glycol, 1,3-butanediol, dipropylene glycol, polyethylene glycol, glycerin, diglycerin, more preferably propylene glycol, 1,3-butanediol, glycerin,
The topical medicine according to any one of <20> to <33>, wherein the polyethylene glycol has a number average molecular weight of 600 or less, preferably 400 or less.
<35> The oil and polyol that are liquid at 20°C of component (d) are selected from hydrocarbon oils, ester oils, silicone oils, and higher alcohols, oils that are liquid at 20°C, alkylene glycol, polyalkylene glycol, The topical medicine according to any one of <20> to <34> above, which is one or more substances selected from polyols selected from glycerin and triglycerin.
<36> A method for treating a disease by transdermal administration, wherein a composition containing component (a), component (b) and component (c) is electrostatically sprayed directly onto the skin to form a film on the skin. A method characterized by:
(a) one or more volatile substances selected from water, alcohols and ketones;
(b) a polymer with film-forming ability;
(c) A medicinal ingredient that can be transdermally administered.
<37> A combination of component (a), component (b) and component (c), wherein a composition containing component (a), component (b) and component (c) is electrostatically sprayed directly onto the skin. A combination characterized in that it is used by forming a film on the skin with
(a) one or more volatile substances selected from water, alcohols and ketones;
(b) a polymer with film-forming ability;
(c) A medicinal ingredient that can be transdermally administered.
<38> Use for the manufacture of an external medicine, wherein a composition containing component (a), component (b) and component (c) is electrostatically sprayed directly onto the skin to form a film on the skin A use for manufacturing an external medicine, characterized by using
(a) one or more volatile substances selected from water, alcohols and ketones;
(b) a polymer with film-forming ability;
(c) A medicinal ingredient that can be transdermally administered.

EXAMPLES The present invention will be described in more detail below with reference to examples. However, the scope of the invention is not limited to such examples. "%" means "% by mass" unless otherwise specified.

[Example 1]
(1) Preparation of spray composition Ethanol (manufactured by Wako Pure Chemical Industries, Ltd.: trade name ethanol (99.5)) was used as the component (a) of the spray composition. Polyvinyl butyral (PVB, trade name: S-LEC B BM-1, manufactured by Sekisui Chemical Co., Ltd.) was used as the component (b) of the spray composition. Felbinac (manufactured by Junsei Chemical Co., Ltd.) was used as the component (c) of the spray composition. Table 1 shows the mixing ratio in the composition for spraying. The amount of ethanol shown in Table 1 is an effective amount and does not contain water.
(2) Electrostatic spray process Using an electrostatic spray device 10 having the configuration shown in FIG. 1 and the appearance shown in FIG. An electrostatic spray method was applied for 180 seconds. The conditions for the electrostatic spray method were as shown below.
・Applied voltage: 30 kV
・Distance between nozzle and skin: 150mm
・Discharge rate of spray composition: 3 mL/h
・Environment: 25°C, 30% RH
This electrostatic spray formed a film on the surface of the skin model in the form of a single sheet of fiber deposits. The coating was a circle about 4 cm in diameter and weighed about 3.8 mg. The fiber thickness measured by the method described above was 660 nm.

[Examples 2 to 12]
An electrostatic spraying step was carried out in the same manner as in Example 1 except that the components (a), (b), (c) and (d) in the spray composition were changed to the conditions shown in Table 1 below, and the fibers were A coating consisting of a deposit of The following materials were used for component (c). Diclofenac (manufactured by Tokyo Chemical Industry Co., Ltd.), loxoprofen (manufactured by Junsei Chemical Co., Ltd.), flurbiprofen (manufactured by Tokyo Chemical Industry Co., Ltd.).

[Example 13]
An electrostatic spraying step was performed in the same manner as in Example 1, except that glycerin (manufactured by Wako Pure Chemical Industries, Ltd.) was used as the component (d) in the spray composition to obtain a coating composed of fiber deposits. . Table 2 shows the mixing ratio in the composition for spraying. The amounts of ethanol, glycerin, and dipropylene glycol shown in Table 2 are effective amounts.

[Examples 14-22]
An electrostatic spraying step was carried out in the same manner as in Example 13 except that the components (a), (b), (c) and (d) in the spray composition were changed to the conditions shown in Table 2 below, and the fibers were A coating consisting of a deposit of The following materials were used for component (d). Dipropylene glycol (DPG, manufactured by Wako Pure Chemical Industries, Ltd.).

[Comparative Example 1]
A sheet of film consisting of a deposit of fibers was obtained in the same manner as in Example 2, except that the same spray composition as in Example 2 was used, and aluminum foil was used instead of a skin model. After holding this film in an environment of 25° C. and 50% RH for 3 days, this film was peeled off from the aluminum foil and applied to a skin model to form a film on the skin model.

[Comparative Example 2-4]
A single film consisting of a fiber deposit was prepared in the same manner as in Example 2, except that the same spray composition as in Examples 5, 8, and 11 was used, and aluminum foil was used instead of a skin model as the spray target. Obtained. As in Comparative Example 1, it was peeled off from the aluminum foil and a film was formed on the skin model.

〔evaluation〕
The films formed in Examples and Comparative Examples were evaluated for the crystalline state of component (c), adhesion to skin, and durability on skin according to the following criteria. The results are shown in Tables 1 and 2.

<Crystal state of component (c)>
For each coating, the crystalline state of the components was confirmed by wide-angle X-ray diffraction (XRD). Specifically, in wide-angle X-ray diffraction, a film in which at least one sharp diffraction peak derived from a medicinal ingredient appeared around a Bragg angle of 15 to 25° was evaluated as crystalline, and the other films were evaluated as amorphous. Measurement conditions were X-ray source Cu/Kα-radiation, tube voltage 40 kV, tube current 15 mA, diffraction angle 5-60°, X-ray scan speed 10°/min (measuring device: MiniFlex 600 manufactured by RIGAKU). In both Examples and Comparative Examples, the measurement was performed within 24 hours after forming the film on the skin model.

<Adhesion to skin>
Adhesion was evaluated by a bending test of a skin model on which a film was formed. With the coating on the outside, bending of 180 degrees was repeated 5 times, and the adhesion between the coating and the skin model was evaluated according to the following criteria.
A: Lifting between the skin model and the membrane, no peeling of the membrane B: Lifting of the membrane occurs only within 10 mm around the bend, but no peeling of the membrane C: The membrane extends beyond 10 mm around the bend. Floating occurs, but no film peeling D: The film completely peels off

<Durability on skin>
Durability was evaluated by a scratch test of the coating. The skin model was fixed, and a load of about 50 gf was applied to the film from the upper surface with the index finger, and the distance of 2 cm was rubbed 5 times in one direction. Durability was evaluated according to the following criteria based on the state of adhesion between the film and the skin model after that and the adhesion to the index finger.
A: There is no peeling, tearing, or adhesion of the film to the index finger. B: There is tearing of the film surface, but there is no adhesion to the index finger. C: There is tearing of the film surface, and there is also adhesion to the index finger. tear and peel off completely

For Examples 1, 10, 15 and 22 and Comparative Examples 1 and 4, film formation was performed in the same manner, except that the object for film formation was changed to pig ear skin. Table 3 shows the results of evaluating the permeability of the component (c) in the formed coating by the following method. The permeability test was started within 24 hours after forming the film.

<Drug permeability test>
An in vitro skin permeation test was performed using pig skin. Specifically, pig skin was mounted on a vertical diffusion cell to measure the amount of component (c) permeated through the skin. That is, the skin removed from pig ear skin (purchased from Tokyo Shibaura Organ Co., Ltd.) was attached to the receptor layer side of the vertical diffusion cell, and the inside was filled with physiological saline. was applied to form a film. Twenty-four hours after application, the receptor fluid was collected, and the drug permeation amount (μg/cm ² ) of the active ingredient was measured by high performance liquid chromatography. Table 3 shows the results.

As is clear from Table 1, Examples 1-12 in which the composition for spraying was directly electrostatically sprayed onto the skin model to form a film compared to Comparative Examples 1-4 in which the film was formed and then applied to the skin model. showed high adhesion and durability. In Examples 1-8 and 10-12, the component (c) in the coating was in an amorphous state. When a film is formed and then applied to the skin as in Comparative Examples 1-4, crystallization of the component (c) proceeds depending on the storage environment. Since a film containing the component (c) is formed, it is possible to coat the skin with a sparingly soluble drug in a highly soluble state. The reason why the component (c) of Example 9 was in a crystalline state is not clear, but it is believed that the content of the component (b) was relatively small and the drying rate was low, so that it did not become amorphous. .

Moreover, as is clear from Table 2, it can be seen that the inclusion of component (d) in the spray composition improves adhesion and durability.

Moreover, as is clear from Table 3, compared to Comparative Examples 1 and 4, in which the film was applied to the skin after forming the film, Examples 1, 10, 15, and 22, in which the film was formed by direct electrostatic spraying, exhibited high adhesion. Therefore, it can be seen that high drug permeability can be obtained.

10 electrostatic spray device 11 low voltage power supply 12 high voltage power supply 13 auxiliary electrical circuit 14 micro gear pump 15 container 16 nozzle 17 conduit 18 flexible conduit 19 current limiting resistor 20 housing

Claims (8)

An external preparation for fibrosis containing component (a), component (b) and component (c), wherein a composition containing component (a), component (b) and component (c) is directly applied to the skin An external medicine characterized in that it is used by electrostatically spraying to form a film consisting of deposits of fibers on the skin.
(a) one or two volatile substances selected from water and ethanol 50% by mass or more and 98% by mass or less,
(b) polyvinyl butyral resin 1% by mass or more and 40% by mass or less,
(c) A medicinal ingredient that can be transdermally administered. The content of the component (b) in the composition is 4% by mass or more and 40% by mass or less,
The topical medicine according to claim 1, wherein the content of said component (a) is 50% by mass or more and 94% by mass or less. 3. The topical medicine according to claim 1, wherein the fiber has a diameter equivalent to a circle of 10 nm or more and 3000 nm or less. The topical medicine according to any one of claims 1 to 3, wherein the mass ratio ((c)/(b)) of said component (c) to said component (b) is 0.01 or more and 20 or less. An external preparation for fibrogenesis containing component (a), component (b) and component (c), wherein a composition containing component (a), component (b) and component (c) is directly applied to the skin An external medicine characterized in that it is used by electrostatically spraying to form a film consisting of deposits of fibers on the skin.
(a) ethanol 50% by mass or more and 98% by mass or less,
(b) polyvinyl butyral resin 1% by mass or more and 40% by mass or less,
(c) A medicinal ingredient that can be transdermally administered. 6. The topical medicine according to claim 5, wherein said component (b) is dissolved or dispersed in said component (a) in said composition. 7. The topical medicine according to claim 5 or 6, wherein said composition further contains water. The step of electrostatically spraying is a step of electrostatically spraying the composition onto the skin using an electrostatic sprayer to form a coating composed of fiber deposits,
The electrostatic spray device comprises a container containing the composition, a nozzle for discharging the composition, a supply device for supplying the composition contained in the container to the nozzle, and a voltage applied to the nozzle. The topical medicine according to any one of claims 1 to 7, comprising a power source for applying

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