JP2022071155A - External preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external preparation that has high percutaneous absorption rate of drug efficacy components and in which drug efficacy components are not eliminated from skin due to external force such as friction with skin, clothing or the like or movement of skin.

SOLUTION: An external preparation is produced by combining (A) external preparation containing a drug efficacy components and polyol which can be percutaneously administered and (B) a composition containing component (a) and component (b). The external preparation is used by directly applying the composition (B) through electrostatic spraying onto skin before or after applying the external preparation (A) onto the skin to form a coating made up of accumulation of fibers. (a) 50 mass% or more of one or more kinds of volatile substance selected from water, alcohol and ketone. (b) 2 mass% or more 40 mass% or less of water-insoluble polymer having coating forming performance.

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

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

As external medicines for transdermal administration, liniments such as ointments, creams, gels, liquids, lotions and tics, and patches such as poultices and tapes are mainly used. For these external medicines, percutaneous absorption of medicinal ingredients is promoted by blending a component that promotes absorption (Patent Documents 1, 2, etc.).

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

International Publication No. 2000/061120 International Publication No. 2001/007018 Japanese Unexamined Patent Publication No. 2006-104211 Special Table 2000-516130 Gazette Japanese Unexamined Patent Publication No. 2014-55119

However, in the case of an external medicine for application, the external medicine applied on the skin disappears from the application site due to contact with the skin, contact with clothing, etc., and a sufficient effect is often not obtained. In addition, in the case of a patch, since the medicinal component is contained in the base such as the matrix of the patch, the release rate from the base to the skin surface is not sufficiently fast, so that rapid percutaneous absorption is possible. Often not done.

The method for treating skin by electrostatic spray described in Patent Document 3 is a method for treating skin by electrostatically applying particles which are particulate powder substances. Therefore, since the film is not a deposit of fibers, it is difficult to maintain the morphology of a single film, the durability is inferior such that particles are partially shed during use, and it is difficult to peel off after use.
On the other hand, in the method of forming a coating by electrostatic spray described in Patent Document 4, since the film to be formed is a deposit of fibers, it can be treated as a single film and can be easily peeled off after use. However, the adhesion between the coating film formed by the electrostatic spray and the substrate is not sufficient, and the coating film may be damaged or peeled off due to an external force such as friction. Further, Patent Document 4 does not describe anything about clearing a film made of a deposit of fibers and coating the skin in a natural state. Further, the drug-containing ultrafine fiber described in Patent Document 5 relates to a method for producing a patch.

Therefore, the subject of the present invention is an external drug having a high transdermal absorption rate of the medicinal ingredient and the medicinal ingredient does not disappear from the skin due to external force such as friction with the skin or clothing or movement of the skin. To provide.

Therefore, as a result of various studies to solve the above problems, the present inventor has found that (A) an external preparation containing a medicinal ingredient that can be administered transdermally, (B) (a) a volatile substance, and (b) a film-forming ability. (A) Before or after applying the external preparation to the skin, (B) the composition may be electrostatically sprayed directly onto the skin to form a film on the skin. For example, the film formed on the skin forms a deposit of fibers, which is not easily destroyed by contact with clothing, skin, or water, does not peel off by bending and stretching of the skin, and has excellent transdermal absorption capacity. He found that a drug could be obtained and completed the present invention.

That is, the present invention is an external medicine obtained by combining (A) an external preparation containing a medicinal ingredient that can be administered transdermally and (B) a composition containing the component (a) and the component (b). The present invention provides an external medicine characterized in that the composition (B) is directly electrostatically sprayed onto the skin to form a film before or after the external preparation (A) is applied to the skin.
(A) One or more volatile substances selected from water, alcohol and ketones,
(B) A polymer having a film-forming ability.

When the external medicine of the present invention is used, a film having a high transdermal absorption rate of the medicinal ingredient is formed on the skin. In addition, the formed film has excellent water resistance and sweat resistance, is not easily destroyed by contact with the skin or clothing, and is not peeled off by bending or stretching of the skin. In addition, the formed film is transparent and does not have an appearance like a patch.

FIG. 1 is a schematic view showing the configuration of an electrostatic spray device preferably used in the present invention. FIG. 2 is a schematic view showing a state in which an electrostatic spray method is performed using an electrostatic spray device.

The external medicine of the present invention includes (A) an external preparation containing a medicinal ingredient that can be administered transdermally (hereinafter, may be referred to as an external preparation (A)), and (B) a component (a) and a component ( It is an external medicine obtained by combining a composition containing b) (hereinafter, may be referred to as a composition (B) or a spraying composition).
(A) One or more volatile substances selected from water, alcohol and ketones,
(B) A polymer having a film-forming ability.

Examples of the external preparation (A) include an external preparation used by applying to the skin containing a medicinal ingredient that can be administered transdermally. Examples of the form of the external preparation include liniments such as ointments, creams, gels, liquids, lotions, and ticks.

The medicinal ingredients used in the external preparation (A) include α-adrenaline receptor blockers, adrenaline receptor stimulants, angiotensin II receptor antagonists, angiotensin converting enzyme inhibitors, calcium antagonists, steroid-based anti-inflammatory / anti-inflammatory analgesics. Drugs, Parkinson's disease remedies, vitamin-related drugs, hormone drugs, sickness / tasting drugs (antifungal drugs), antipyretic analgesics, external hemorrhoids, coronary vasodilators, bronchial dilatation / antitussives, cardiotonics, angina Disease treatment drugs, local anesthetics, hypoglycemic drugs, oropharyngeal drugs, psychotropic drugs, antiallergic drugs, antihistamine drugs, antibacterial drugs, anti-insect / anti-insect / pesticides, anti-arrhythmic drugs, anti-vomiting drugs, hyperlipidemia Disease remedies, bactericides, hemostatics, women's medicines, disinfectants, sleeping pills, tissue respiration activators, antipruritic and anti-inflammatory agents, isotonic solutions, skin disease remedies, non-steroidal anti-inflammatory / anti-inflammatory analgesics, moisturizers, Examples include erectile dysfunction treatments, anesthetics, peripheral vasodilators, immunosuppressants, hair medicines, diuretics, enema agents, and quitting aids. Of these, adrenaline receptor stimulants, steroidal anti-inflammatory / anti-inflammatory analgesics, vitamin-related drugs, external hemorrhoids, bronchial dilatation / antitussives, local anesthetics, oropharyngeal drugs, psychiatric drugs, antiallergic drugs, antihistamines. Drugs, antibacterial drugs, anti-insect / anti-insect / pesticides, bactericides, hemostatics, women's drugs, disinfectants, tissue respiration activators, antipruritic and anti-inflammatory agents, isotonic solutions, skin disease remedies, non-steroidal anti-inflammatory / At least one selected from anti-inflammatory analgesics, moisturizing agents, anesthetics, immunosuppressants, and hair medicines is preferable.

Examples of α-adrenaline receptor blockers include urapidil, terrazosin hydrochloride, bunazosin hydrochloride, prazosin hydrochloride, doxazocin mesylate, bisoprolol fumarate, propranolol hydrochloride, chilisolol hydrochloride, bufetrol hydrochloride, buplanolol hydrochloride, etc. Athenolol, Indenolol Hydrochloride, Alprenolol Hydrochloride, Oxprenolol Hydrochloride, Carteolol Hydrochloride, Nadrol, Pindolol, Timorol Maleate, Nipradilol, Bunitrolol Hydrochloride, Pembutrol Sulfate, Bopindolol Maronate, Examples thereof include metoprolol tartrate, betaxolol hydrochloride, bevantrol hydrochloride, and acebutrol hydrochloride.

Adrenaline receptor stimulants include epinephrine, norepinephrine, dopamine hydrochloride, phenilefurin hydrochloride, ethyrefrin hydrochloride, efedrin hydrochloride, methylephedrine hydrochloride, chronidine hydrochloride, methyldopa, guanabends acetate, guanfacin hydrochloride, isoprenaline hydrochloride. , Examples thereof include clembuterol hydrochloride, mabuterol hydrochloride, isoxpurine hydrochloride, methanefetamine hydrochloride, methylphenylate hydrochloride, pemoline, imipramine hydrochloride, and amedinium methylsulfate. And among these, at least one selected from ephedrine hydrochloride is preferable.

Examples of the angiotensin II receptor antagonist include losartan potassium, candesartan, candesartan cilexetil, olmesartan medoxomil, and irbesartan.

Examples of angiotensin-converting enzyme inhibitors include alacepril, captopril, delapril hydrochloride, quinapril hydrochloride, benazepril hydrochloride, cilazapril hydrate, enalapril maleate, trandolapril, imidapril hydrochloride, lisinopril hydrate, and perindopril erbumin. , Temocapril hydrochloride, ramipril and the like.

Calcium channel blockers include verapamil hydrochloride, diltiazem hydrochloride, bepridil hydrochloride, crenchazem, nifedipine, nicardipine hydrochloride, ferrodipine, nisoldipine, cilnidipine, aranidipine, benidipine hydrochloride, manidipine hydrochloride, nilvadipine, nitrendipine, varnidipine hydrochloride. , Ehonidipine hydrochloride.

Hydrocortisone butyrate, prednisolone valerate acetate, methylbrednizolone, hydrocortisone acetate, fluosinolone acetonide, triamcinolone acetonide, dexamethasone, betamethasone valerate, and diflucolt are examples of steroidal anti-inflammatory and anti-inflammatory analgesics. Ron valerate, clobetazole propionate, fluoronide, halcinonide, dexamethasone acetate, dexamethasone acetate, tetrahydrozoline hydrochloride, amcinonide, alchrometasone propionate, clobetazone butyrate, diflupredonate, diflorazone acetate, dexamethasone valerate. , Deprodon propionic acid ester, prednisolone, prednisolone acetate, dexamethasone propionic acid ester, betamethasone dipropionic acid ester, mometazone furancarboxylic acid ester, butyric acid propionic acid hydrocortisone, betamethasone butyric acid ester propionic acid ester. Among these, hydrocortisone butyrate, prednisolone valerate acetate, fluosinolone acetonide, triamcinolone acetonide, dexamethasone, diflucortron valerate, clobetazol propionate, fluorinide, halcinonide, dexamethasone acetate, hydrochloric acid. Tetrahydrozoline, amcinonide, alchrometazone propionate, clobetazone butyrate, diflupredonate, diflorazone acetate, dexamethasone valerate, deprodonpropionate, prednisolone, prednisolone acetate, dexamethasone propionate, betamethasone dipropionate More preferably, at least one selected from esters, mometazone furancarboxylic acid esters, butyric acid propionate hydrocortisone, betamethasone butyric acid ester propionic acid esters.

As therapeutic agents for Parkinson's disease, trihexyphenidyl hydrochloride, profenamine hydrochloride, pyroheptin hydrochloride, mazaticol hydrochloride, metixene hydrochloride, viperidene hydrochloride, amantazine hydrochloride, levodopa, carbidopa, venceramide, droxydopa, bromocriptine mesylate. , Talipexol hydrochloride, cabergolin, pergolidemesilate, selegiline hydrochloride.

Vitamin-related drugs include Vitamin A, Vitamin D, Vitamin E, Vitamin K, Phytonadion, Alpha Calcidol, Eldecalcitol, Calcitriol, Falecalcitriol, Retinol palmitate, Ergocalciferol, Colecalciferol, Phosphoric acid. Calcium hydrogen, calcium hydrogen phosphate hydrate, retinol, calcium lactate, calcium lactate hydrate, tretinone, refined eel oil, ascorbic acid, d-α-tocopherol, sodium L-ascorbic acid, calcium ascorbic acid, Sodium ascorbic acid, ascorbic acid powder, ascorbic acid powder, orotic acid, nicotinic acid amide, vitamin C, riboflavin, riboflavin butyrate, ascorbic acid for direct hit, calcium pantothenate, vitamin A oil, tocopherol, d-α-tocopherol succinct Acid ester, d-α-tocopherol acetate, succinic acid d-α-tocopherol, tocopherol succinate calcium, nicotinic acid, pyridoxin hydrochloride, d-α-tocopherol acetate, d-α-tocopherol acetate powder, riboflavin butyrate, RIKEN Dry EB500d-GP, pantenol, pyridoxin hydrochloride, retinol acetate, liver oil, strong liver oil, dl-α-tocopherol succinate, thiamine hydrochloride, thiamine nitrate, bistiamine nitrate, thiamine disulfide, thiamine disetyl sulfate, hydrochloric acid Disetiamine, Flusultiamine Hydrochloride, Octothamine, Sicothamine, Bisibuchiamine, Bisbenchamine, Flusultiamine, Prosultiamine, Benfothamine, Flavin Adenine Dinucleotide Sodium, Riboflavin Sodium Phosphate, Pyridoxal Phosphate, Hydroxocobalamine Hydrochloride , Hydroxocobalamine acetate, Cyanocobalamine, Hydroxobalamine, Sodium pantothenate, Biotin, Potassium ascorate / magnesium equal amount mixture, Inositol hexanicotinate, Ursodesoxycholic acid, L-Cycrate hydrochloride, L-cysteine, Gamma oryzanol, Calcium glycerophosphate , Calcium gluconate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, glucuronolactone, glucuronic acid amide, chondroitin sodium sulfate, processed ascorbic acid, carrots, yoquinin. Among these, vitamin A, phytonadione, alphacalcidol, erdecalcitol, carcitriol, phalecalcitriol, retinol palmitate, ergocalciferol, chorecalciferol, calcium hydrogenphosphate, calcium hydrogenphosphate water. Japanese products, retinol, calcium lactate, calcium lactate hydrate, tretinone, refined eel oil, ascorbic acid, d-α-tocopherol, sodium L-ascorbic acid, calcium ascorbic acid, sodium ascorbic acid, ascorbic acid powder, Ascorbic acid powder, orotic acid, nicotinic acid amide, vitamin C, riboflavin, riboflavin butyrate, ascorbic acid for direct hit, calcium pantothenate, vitamin A oil, tocopherol, d-α-tocopherol succinate, d-α-tocopherol Acetate ester, d-α-tocopherol succinate, tocopherol succinate calcium, nicotinic acid, pyridoxin hydrochloride, d-α-tocopherol acetate, d-α-tocopherol acetate powder, riboflavin butyrate, RIKEN dry EB500d-GP, bread At least one selected from tenol, pyridoxin hydrochloride, and L-cysteine is preferable.

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

Examples of drugs (antifungal agents) for mizumushi and tamushi include undesicylene acid, zinc undesyleneate, phenyl-11-iodo-10-undecinoate, exalamide, clotrimazole, econazole nitrate, myconazole nitrate, thioconazole, zinc diethyldithiocarbamate, Cyclopyrox olamine, siccanin, tricomycin, pyrrolnitrin, thiantoll, 2,4,6-tribromphenylcaproic acid ester, trimethylcetylammonium pentachlorophenate, toluciclate, tornaftoate, haloprodine, bark (protozoan equivalent) ), Velverin benzoate, decalinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate solution, decalinium acetate, hinokithiol, levulinine, benzoic acid, chlorobutanol, acetic acid, phenol, iodotinki, diphenylpyralin hydrochloride, diphenylimidazoline salicylate, chlorpheni maleate Examples thereof include lamin, dibukine hydrochloride, prokine hydrochloride, lidocaine hydrochloride, aldioxa, glycyrrhizinic acid and its salts, cicon (primary drug equivalent), touki (primitive drug equivalent), timole, dragon brain, diethyl phthalate, and chlorohydroxyaluminum.

Antipyretic analgesics include aspirin sodium, ethenzamid, allylisopropylurea, sodium benzoate caffeine, caffeine, vitamin B1 and its derivatives and their salts, vitamin B2 and its derivatives and their salts, aminoacetic acid, magnesium silicate, synthetic. Aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel (as dry aluminum hydroxide gel), dry aluminum hydroxide gel, earth dragon, kanzo, keihi, Examples include shakuyaku, sansho, and shokyo.

Drugs for external hemorrhoids include citrus seed extract, ethyl aminobenzoate, parabutylaminobenzoate diethylaminoethyl hydrochloride, meprilkine hydrochloride, oxypolyethoxydodecane, funnel extract, epinephrine solution, nafazoline hydrochloride, hydrocortisone, tannic acid, acrinol. , Alkylpolyaminoethylglycine, decalinium chloride, velverin chloride hydrate, cetrimid, resorcin, sulfaziazine, sulfisomidin, sulfisomidin sodium, homosulfamine, chlorpheniramine maleate, aluminum chlorhydroxyalantinate, ictamol , Resoteam chloride, dry potassium aluminum sulfate, purified egg yolk lecithin, egg yolk oil, potassium aluminum sulfate, cicon, citrus seeds, hamamelis, processed daisan, d-kanfuru, dl-kanfuru, peppermint oil, dl-menthol. Among these, at least one selected from horse chestnut seed extract, d-camphor, dl-camphor, and dl-menthol is preferable.

Examples of coronary vasodilators include etaphenone hydrochloride, trimetazidine hydrochloride, trapidil, and nicorandil.

As the bronchodilator / antitussive, dl-methylephedrine hydrochloride is preferable.

Examples of cardiotonic agents include digitoxin, digoxin, methyldigoxin, lanatoside C, prosciralidine, dobutamine hydrochloride, docarpamine, denopamine, aminophylline hydrate, milrinone, vesnarinone, pimobendan, and ubidecalenone.

Examples of the therapeutic agent for angina include amyl nitrite, nitroglycerin, isosorbide nitrate, dilacep hydrochloride, and dipyridamole.

Local anesthetics include lidocaine, mepivacaine, bupivacaine, ropivacaine, and levopivacaine. And among these, lidocaine is preferable.

Hypoglycemic agents include glybenclamid, glycladide, glymepyride, repaglinide, nateglinide, mitiglinide calcium hydrate, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose, miglitol, pioglitazone hydrochloride, troglitazone.

As the oropharyngeal drug, chlorhexidine hydrochloride and sodium azulene sulfonate are preferable.

As psychotropic drugs, chlorpromazine hydrochloride, perazinemaleate, levomepromazinemaleate, trifloperazine hydrochloride, prochlorperazinemaleate, perphenazine, flufenazinemaleate, thioridazine hydrochloride, thiothixene, Carpipramine Hydrochloride, Clocaplamin Hydrochloride Hydrate, Mosapramine Hydrochloride, Zotepine, Haloperidol, Spiperone, Timiperon, Bromperidol, Pimodide, Oxypertin, Sulpyrido, Slutpride Hydrochloride, Thiaprid Hydrochloride, Nemonapride, Perospyron Hydrochloride, Quetiapine Fumalate , Lisperidone, olanzapine, propericiadin, clothiazepam, etizolam, alprazolam, lorazepam, bromazepam, chlordiazepoxide, diazepam, oxazolam, cloxazolam, fludiazepam, mexazolam, ethyl lofrazepate, chromipramine hydrochloride Salt, Amoxapine, Doslepine Hydrochloride, Maprotyrin Hydrochloride, Myanserin Hydrochloride, Sepiptyrin Maleate, Fluboxamine Maleate, Paloxetine Hydrochloride Hydrate, Milnaciplan Hydrochloride, Trazodone Hydrochloride, Lithium Carbonate, Hydroxyzine Pamoate , Hydroxidine hydrochloride can be mentioned. Among these, hydroxyzine pamoate and hydroxyzine hydrochloride are preferable.

Anti-allergic agents include pemirolast, sodium cromoglycate, tramalast, anlexanox, azelastin, ketotifen, mekitadine, fexofenadine, epinastin, epastin, cetirizine, levosetilizine, bepotastine, emedastine, olopatadine, loratadine, desloratadine. , Montelukast, Suplatast tosilate, Tranilast. Among these, sodium cromoglycate, mequitazine, loratadine, suplatast tosilate, and tranilast are preferable.

Antihistamines include diphenhydramine, chlorpheniramine, promethazine, hydroxyazine, cyproheptazine, cremastine, diphenylpyralinteocrate, diphenhydramine tannate, azelastin hydrochloride, epinastine hydrochloride, oxatomide, oropatazine hydrochloride, ketotiphenfumarate. , Diphenhydramine Hydrochloride, Ciproheptazine Hydrochloride Hydrate, Fexophenazine Hydrochloride, Fumalate, Bepotastine Besilate, Alimemazine Tartrate, Cremastine Fumalate, Chlorpheniramine Maleate, Diphenylpyraline Hydrochloride, Tripro Examples thereof include lysine hydrochloride hydrate, sodium riboflavin phosphate, homochlorcyclidine hydrochloride, evastin, cetilysin hydrochloride, levosetilidine hydrochloride, and emedastin fumarate. Among these, diphenhydramine, promethazine, diphenylpyraline theocrate, diphenhydramine tannate, azelastin hydrochloride, epinastine hydrochloride, oxatomide, olopatazine hydrochloride, ketotiphenfumarate, diphenhydramine hydrochloride, cypropheptazine hydrochloride hydrate. , Fexophenazine hydrochloride, Bepotastine besilate, Alimemazine tartrate, Cremastine fumarate, Chlorpheniramine maleate, Diphenylpyraline hydrochloride, Triprolysine hydrochloride hydrate, Sodium riboflavin phosphate, Homochlor Cyclydin hydrochloride, evastin, cetilidine hydrochloride, levosetilidine hydrochloride, and emedastin fumarate are preferred.

Antibacterial agents include penicillin, cephem, carbapenem, monobactam, penem, aminoglycoside, phosphomycin, chloramphenicol, macrolide, glycopeptide, quinolone, new quinolone, sulfa, and fradiomycin. Examples thereof include sulfate, gentamicin sulfate, penicillin isethionate, and sulfaziazine silver. Among these, chloramphenicol-based, fradiomycin sulfate, gentamicin sulfate, pentamidine isethionate, and silver sulfadiazine are preferable.

Anti-insect / pesticide / pesticides include 2-undecanone, p-menthan-3,8-diol, atobacon / proguanyl hydrochloride, icaridine, eugenonal, orange oil, geraniol, citral, citronellal, citronellol, sulfametoxa. Zol Trimetoprim, Pinen, Ethyl Butylacetylaminopropionate, Milsen, Metoflutrin, Linarol, Limonen, Lemon Eucalyptus Essential Oil, Albendazole, Pradicantel, Phenotrin, Santonin, Pyrbinium Pamoate, Macri, Pirantel Pamoate, Tinidazole, Kinine Hydrochloride Hydration Things, primaquin phosphate, mefroquin hydrochloride, diethylcarbamazine citrate, metronidazole, d, d-T-ciphenotrin, amidoflumeth, imiprotoline, orthodichlorobenzene, dichlorvos, diazinone, diet, trichlorfon, hydramethylnone, piper Ronylbutoxide, pyriproxyfen, pyretrin, fenitrothione, fenthion, phthalthrin, propetanphos, propoxul, permethrin, metoxadiazone, metoprene, benzyl benzoate, pesticide chrysanthemum extract (total pyretrin), paromomycin sulfate, ibermectin, mebendazole, quinic acid, adipine Acid piperazine, citrate piperazine, piperazine hexahydrate, apple acid piperazine, phosphate piperazine, sulfur, dioctylsodium sulfosuccinate, aloe, senna, daiou, aminoethylsulfonic acid, bile extract (powder), bile powder, dehydro Sulfonic acid, piperazine, piperazine, eucalyptus oil can be mentioned. Among these, p-menthane-3,8-diol, icaridin, ethyl butylacetylaminopropionate, and DEET are preferable.

Antiarrhythmic agents include quinidine sulfate hydrate, azimarin, procainamide hydrochloride, disopyramide, pyrumenol hydrochloride, cibenzoline succinate, mexiletine hydrochloride, propafenone hydrochloride, pyrudikinide hydrochloride, sotalol hydrochloride, amiodarone hydrochloride. Can be mentioned.

Examples of the anti-vomiting agent include granisetron hydrochloride, azacetron hydrochloride, ondansetron hydrochloride, ramosetron hydrochloride, and tropisetron hydrochloride.

Examples of the therapeutic agent for hyperlipidemia include pravastatin sodium, simvastatin, fluvastatin sodium, atorvastatin calcium, rosvastatin calcium, pitavastatin calcium, cuclofibrate aluminum, clinofibrate, bezafibrate, fenofibrate, nicomol, niceritrol, probucol, and ezetimib. ..

As the bactericidal agent, chlorhexidine gluconate, sodium copper chlorophyllin, isopropylmethylphenol, cetylpyridinium chloride hydrate, benzethonium chloride, and benzalkonium chloride are preferable.

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

As the drug for women, DL-methionine, tocopherol powder (50%), and royal jelly are preferable.

As the disinfectant, iodine and cresol are preferable.

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

As the tissue respiration activator, solcoceryl is preferable.

Examples of antipruritic and anti-inflammatory agents include crotamiton, cortisone acetate, isothipendyl hydrochloride, glycol salicylate, benzalconium chloride, caramine, d-borneol, and aqueous ammonia. And among these, crotamiton is preferable.

As the isotonic solution, a physiological saline solution is preferable.

As the therapeutic agent for skin diseases, trafermin, etretinate, maxacalcitol, alcroxa, sodium bucladecine, alprostadil alphadex, tretinotocopheryl, and purified sucrose are preferable.

Non-steroidal anti-inflammatory / anti-inflammatory analgesics include salicylic acid, aspirin, sulpyrine hydrate, acetaminophen, diclofenac sodium, fenvphen, ibuprofen, aminoprofen, loxoprofen sodium hydrate, naproxen, oxaprofen, ketoprofen, Thiaprofenic acid, slindac, aluminum flufenamic acid, fervinac, mephenamic acid, indomethacin, indomethacin farnesyl, acemethasin, progourmet tacinmaleate, bendazac, pyroxicum, ampyroxycam, lornoxicum, tenoxycam, meroxycam, flurbiprofen, etodrac, thiaramid hydrochloride. Salt, bucolome, loxoprofen sodium, flurbiprofen, esflurbiprofen, methyl salicylate, lysoteam hydrochloride, bromeline, diphenhydramine hydrochloride, dibukine, dimethylisopropylazulene, benzethonium chloride, dipotassium glycyrrhizinate, l-menthol, zinc oxide , Allantin, heparin analogs, glycyrrhizic acid. Among these, diclofenac sodium, loxoprofen sodium hydrate, ketoprofen, felbinac, indomethacin, pyroxycam, loxoprofen sodium, flurbiprofen, esflurbiprofen, methyl salicylate, lysoteam hydrochloride, bromelain, l-menthol. , Zinc oxide, allantin, heparin analog, glycyrrhetinic acid are preferred.

Examples of the moisturizer include white vaseline, glycerin, propylene glycol, 1,3-butylene glycol, sorbitol, pyrrolidone carboxylate, urea, and hyaluronic acid. Among these, white petrolatum and glycerin are preferable.

Examples of the erectile dysfunction therapeutic agent include sildenafil citrate, vardenafil hydrochloride, and tadalafil.

Anesthetics include benzocaine, procaine hydrochloride, lidocaine hydrochloride, tetracaine hydrochloride, chloroprocaine, mepivacaine hydrochloride, dibucaine hydrochloride, bupivacaine hydrochloride, droperidol, fentanylcitrate. Among these, lidocaine hydrochloride and dibucaine hydrochloride are preferable.

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

Examples of immunosuppressive agents include tacrolimus and tacrolimus hydrate. And among these, tacrolimus hydrate is preferable.

As the hair medicine, carpronium chloride hydrate, finasteride, dutasteride, kashu tincture, panax japonicus tincture, and minoxidil are preferable.

Diuretics include ventilhydrochlorothiazide, trichlormethiazide, methiclothiazide, etaclinic acid, indapamide, chlortalidone, tripamide, methiclan, mefluside, piretanide, furosemide, bumetanide, torasemide, azosemide, potassium canlenoate, spironolactone, triamterene. Will be.

Examples of the enema include D-sorbitol and bisacodyl.

Nicotine is mentioned as a smoking cessation aid.

The medicinal ingredient may be used alone or in combination of two or more depending on the use of the external preparation (A). For example, in the case of an anti-inflammatory analgesic external preparation, a combination of a steroidal anti-inflammatory / anti-inflammatory analgesic, a non-steroidal anti-inflammatory / anti-inflammatory analgesic, a local anesthetic, a vitamin-related drug, a refreshing agent such as menthol, etc. should be blended. Can be done. If it is an external preparation for infectious skin diseases, it can be blended in combination with an antibacterial agent, a refreshing agent, a steroidal anti-inflammatory agent and the like. For external preparations for atopic skin treatment, steroidal anti-inflammatory / anti-inflammatory analgesics, non-steroidal anti-inflammatory / anti-inflammatory analgesics, local anesthetics, immunosuppressants, antihistamines, antiallergic agents, moisturizers, vitamin-related Can be combined with medicines. If it is an athlete's foot / ringworm drug, it can be blended in combination with an antifungal agent, an antihistamine, a local anesthetic, and the like. If it is an external preparation for hemorrhoids, a steroidal anti-inflammatory agent, a hemostatic agent, a non-steroidal anti-inflammatory / anti-inflammatory analgesic, an antihistamine, and the like can be combined and blended.

The content of the medicinal ingredient in the external preparation (A) varies depending on the type of the medicinal ingredient and the dosage form of the external preparation (A), but from the viewpoint of improving the medicinal effect, water resistance, abrasion resistance, bending and stretching resistance, etc. Therefore, 0.0001% by mass or more is preferable, 0.001% by mass or more is more preferable, and 0.01% by mass or more is further preferable. Further, from the viewpoint of improving the stability of the medicinal ingredient, 10% by mass or less is preferable, 20% by mass or less is more preferable, and 30% by mass or less is further preferable. The content of the medicinal ingredient is preferably 0.0001% by mass or more and 0.001% by mass or less, more preferably 0.01% by mass or more and 10% by mass or less, and 20% by mass or more and 30% by mass or less in the external preparation (A). The following is more preferable.

The external preparation (A) can contain various base components depending on the type of dosage form. Examples of such components include water, oils, emulsifiers, thickeners, gelling agents, polyols, alcohols, preservatives, fragrances, antioxidants, stabilizers and the like.

The spraying composition (composition (B)) contains the above-mentioned components (a) and (b).

The volatile substance of the component (a) is a substance having volatile state in a liquid state. In the spray composition, the component (a) is sufficiently charged in the electric field and then discharged from the tip of the nozzle toward the skin, and the component (a) evaporates. The charge density of the spray composition becomes excessive, and the component (a) further evaporates while further becoming finer due to the repulsion of Coulomb, and is finally blended for the purpose of forming a dry film on the skin. For this purpose, the vapor pressure of the volatile substance 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 at 20 ° C., and 0. 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 the component (a), for example, a monovalent chain fatty alcohol, a monovalent cyclic fatty alcohol, and a monovalent aromatic alcohol are preferably used as the alcohol. C ₁ to C ₆ alcohols are used as monohydric chain aliphatic alcohols, C ₄ to C ₆ ring alcohols are used as monohydric cyclic aliphatic alcohols, and benzyl alcohols and phenyls are used as monovalent aromatic alcohols. Ethyl alcohol and the like can be mentioned respectively. Specific examples thereof include ethanol, isopropyl alcohol, butyl alcohol, phenylethyl alcohol, n-propanol, n-pentanol and the like. As these alcohols, one kind or two or more kinds selected from these can be used.

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

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

The content of the component (a) in the spray composition is preferably 50% by mass or more, more preferably 55% by mass or more, and further preferably 60% by mass or more. Further, it is preferably 98% by mass or less, more preferably 96% by mass or less, and further preferably 94% by mass or less. The content of the component (a) in the spray composition 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 or less. The following is more preferable. By containing the component (a) in the spraying composition at this ratio, the spraying composition can be sufficiently volatilized when the electrostatic spraying method is performed.

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

As the polymer having a film-forming ability, an appropriate polymer is used depending on the properties of the volatile substance of the component (a). Specifically, polymers having a film-forming ability are roughly classified into water-soluble polymers and water-insoluble polymers. As used herein, the term "water-soluble polymer" refers to 0. A polymer having the property of dissolving 5 g or more in water. On the other hand, in the present specification, the term "water-insoluble polymer" refers to 0 of the soaked polymer after weighing 1 g of the polymer in an environment of 1 atm and 23 ° C. and then immersing it in 10 g of ion-exchanged water. It means a polymer having the property that 0.5 g or more does not dissolve.

Examples of the polymer having a water-soluble film-forming ability include purulan, hyaluronic acid, chondroitin sulfate, poly-γ-glutamic acid, modified corn starch, β-glucan, glucooligosaccharide, heparin, keratosulfate and other mucopolysaccharides, cellulose and pectin. , Xylan, lignin, glucomannan, galacturonic acid, psyllium seed gum, tamarind seed gum, arabic gum, tragant gum, soybean water-soluble polysaccharide, alginic acid, carrageenan, laminaran, agarose, fucoidan, methylcellulose, hydroxypropylcellulose, hydroxypropyl Examples thereof 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 and the like. 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 a coating film. When polyethylene oxide is used as the water-soluble polymer, its number average molecular weight is preferably 50,000 or more and 3 million or less, and more preferably 100,000 or more and 2.5 million or less.

On the other hand, examples of the water-insoluble polymer having a film-forming ability include fully saponified polyvinyl alcohol that can be insolubilized after film formation, partially saponified polyvinyl alcohol that can be cross-linked after film formation by using in combination with a cross-linking agent, and poly (N-propa). Noylethyleneimine) Graft-dimethylsiloxane / γ-aminopropylmethylsiloxane Copolymer and other oxazoline-modified silicones, polyvinylacetal diethylaminoacetate, zein (main component of corn protein), polyester, polylactic acid (PLA), polyacrylonitrile resin, Examples thereof include acrylic resins such as polymethacrylic acid resins, polystyrene resins, polyvinyl butyral resins, polyethylene terephthalates, polybutylene terephthalates, polyurethane resins, polyamide resins, polyimide resins, and polyamideimide resins. 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 when used in combination with a cross-linking agent, polyvinyl butyral resin, (alkyl acrylate octylamide) It is preferable to use an acrylic resin such as a polymer, an oxazoline-modified silicone such as a poly (N-propanoylethyleneimine) graft-dimethylsiloxane / γ-aminopropylmethylsiloxane copolymer, polyvinyl acetal diethylaminoacetate, zein and the like.

The content of the component (b) in the spray composition is preferably 2% by mass or more, more preferably 4% by mass or more, and further preferably 6% by mass or more. Further, it is preferably 50% by mass or less, more preferably 45% by mass or less, and further preferably 40% by mass or less. The content of the component (b) in the spray composition is preferably 2% by mass or more and 50% by mass or less, more preferably 4% by mass or more and 45% by mass or less, and 6% by mass or more and 40% by mass or less. The following is more preferable. By blending the component (b) in the spray composition at this ratio, it is composed of fiber deposits, has excellent water resistance, sweat resistance, abrasion resistance, bending and elongation resistance, and releases medicinal properties. A good coating can be successfully formed.

The spraying composition may contain only the above-mentioned components (a) and (b), or may contain other components in addition to the components (a) and (b). good. Other components include, for example, coloring pigments, extender pigments, dyes, surfactants having an HLB value of more than 10, UV protective agents, fragrances, repellents, antioxidants, stabilizers, preservatives, antiperspirants, and various other components. Examples include vitamins. In addition, each of these agents is not limited to the use as each agent, and other uses, for example, an antiperspirant can be used as a fragrance depending on the purpose. Alternatively, it can be used in combination with other uses, for example, as an antiperspirant and a fragrance. When other components are contained in the spray composition, the blending 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 more preferable to have.

The external medicine of the present invention is used by directly electrostatically spraying the spraying composition (composition (B)) on the skin before or after applying the external preparation (A) to the skin to form a film.

First, the means for applying the external preparation (A) to the skin depends on the dosage form of the external preparation, and is applied to the skin, sprayed, or the like.

The spray composition is directly electrostatically sprayed to form a film before or after application of the external preparation (A) to the skin. After applying the external preparation (A) to the skin, it is preferable to directly electrostatically spray the application site from the viewpoint of improving the effect development, friction resistance, bending and elongation resistance, etc. of the medicinal ingredient.

When the electrostatic spray method is performed, a composition for spraying having a viscosity of preferably 1 mPa · s or more, more preferably 10 mPa · s or more, still more preferably 50 mPa · s or more at 25 ° C. is used. Further, those having a viscosity at 25 ° C. of preferably 5000 mPa · s or less, more preferably 2000 mPa · s or less, still more preferably 1500 mPa · s or less are used. The viscosity of the spray composition 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 further preferably 50 mPa · s or more and 1500 mPa · s or less at 25 ° C. Is. By using a spray composition having a viscosity in this range, a coating, particularly a porous coating consisting of a deposit of fibers, can be successfully formed by the electrostatic spray method. The formation of a porous film prevents stuffiness of the skin, improves the transdermal absorption capacity of medicinal ingredients, improves the adhesion and followability of the medicinal ingredient to the skin, improves the uniformity and durability of the medicinal ingredient to the skin, and is used for clothing and external use. It is advantageous from the viewpoint of reducing the sticky feeling due to contact with the agent and water resistance. The viscosity of the spray composition 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. In that case, the rotor is No. 43 can be used.

The spray composition is sprayed directly onto human skin by electrostatic spraying. The electrostatic spray method includes a step of electrostatically spraying a spray composition onto the skin to form a film by using an electrostatic spray device in the electrostatic spray step. The electrostatic spray device includes a container for containing the spray composition, a nozzle for discharging the spray composition, a supply device for supplying the spray composition contained in the container to the nozzle, and a voltage to the nozzle. With a power supply to apply. Preferably, FIG. 1 shows a schematic diagram showing the configuration of an electrostatic spray device suitably 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 V to a dozen V. For the purpose of increasing the portability of the electrostatic spray device 10, the low voltage power supply 11 is preferably composed of one or two or more batteries. Further, by using the battery as the low voltage power source 11, there is an advantage that the battery can be easily replaced as needed. Instead of the battery, an AC adapter or the like can be used as the low voltage power supply 11.

The 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 includes an electronic circuit (not shown) that boosts the voltage generated by the low voltage power supply 11 to a high voltage. The step-up electronic circuit is generally composed of a transformer, a capacitor, a semiconductor element, and the like.

The electrostatic spray device 10 further includes an auxiliary electric 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. Further, the auxiliary electric circuit 13 has a function of controlling the rotation speed of the motor provided in the micro gear pump 14 described later. By controlling the rotation speed of the motor, the supply amount of the spray composition from the container 15 of the spray composition described later to the micro gear pump 14 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 started / stopped by turning the switch SW on and off.

The electrostatic spray device 10 further includes a nozzle 16. The nozzle 16 is made of various conductors such as metal and non-conductors such as plastic, rubber, and ceramic, and has a shape capable of ejecting the spray composition from the tip thereof. A minute space through which the spray composition flows is formed in the nozzle 16 along the longitudinal direction of the nozzle 16. The size of the cross section of this microspace is preferably 100 μm or more and 1000 μm or less in terms of diameter. The nozzle 16 communicates with the micro gear pump 14 via a conduit 17. The conduit 17 may be a conductor or a non-conductor. Further, 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, in order to prevent an excessive current from flowing when the human body directly touches the nozzle 16, the nozzle 16 and the high voltage power supply 12 are electrically connected via a current limiting resistance 19.

The micro gear pump 14 communicating with the nozzle 16 via the 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 supplied from the low voltage power supply 11. Further, the micro gear pump 14 is configured to supply a predetermined amount of the spray composition to the nozzle 16 under the control of the auxiliary electric circuit 13.

A container 15 is connected to the micro gear pump 14 via a flexible pipeline 18. The spraying composition is contained in the container 15. The container 15 preferably has a cartridge-type replaceable form.

The electrostatic spray device 10 having the above configuration can be used, for example, as shown in FIG. FIG. 2 shows a handy type electrostatic spray device 10 having dimensions that can be gripped with one hand. In the electrostatic spray device 10 shown in the figure, all the members in the configuration diagram shown in FIG. 1 are housed in a cylindrical housing 20. A nozzle (not shown) is arranged at one end 10a of the housing 20 in the longitudinal direction. The nozzles are arranged in the housing 20 so that the blowing direction of the composition coincides with the vertical direction of the housing 20 and becomes convex toward the skin side, which is the film-forming object. Since the tip of the nozzle is arranged so as to be convex toward the film-forming object in the vertical direction of the housing 20, the spray composition is less likely to adhere to the housing, and a 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 a film on the own skin by the electrostatic spray, grasps the device 10 by hand. Then, one end 10a of the device 10 in which the nozzle (not shown) is arranged is directed to the target portion to be electrostatically sprayed. FIG. 2 shows a state in which one end 10a of the electrostatic spray device 10 is directed toward the inside of the forearm portion of the user. Under this state, the switch of the device 10 is turned on to perform the electrostatic spray method. When the device 10 is turned on, an electric field is generated between the nozzle and the skin. In the embodiment shown in FIG. 2, a positive high voltage is applied to the nozzle, and the skin becomes the negative electrode. When an electric field is generated between the nozzle and the skin, the spray composition at the tip of the nozzle is polarized by electrostatic induction to form a cone at the tip, and droplets of the spray composition charged from the tip of the cone. Is ejected into the air toward the skin along the electric field. When the component (a), which is a solvent, evaporates from the spray composition discharged and charged into the space, the charge density on the surface of the spray composition becomes excessive and spreads in the space while repeating miniaturization due to the Coulomb repulsive force. , Reach the skin. In this case, by appropriately adjusting the viscosity of the spraying composition, the sprayed composition can reach the skin in the form of droplets. Alternatively, while being discharged into the space, the component (a) of the volatile substance as a solvent is volatilized from the composition to solidify the polymer having a film-forming ability as a solute, while being elongated and deformed by a potential difference. Fibers can also be formed and deposited on the surface of the skin. For example, increasing the viscosity of the spray composition tends to deposit the composition on the surface of the skin in the form of fibers. This forms a film of fiber deposits on the surface of the skin. A coating of fiber deposits 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 of film formation, and the nozzle. However, since the impedance is very large, the current flowing through the human body is extremely small. For example, the present inventor has confirmed that the current flowing through the human body during the electrostatic spray method is several orders of magnitude smaller than the current flowing through the human body due to static electricity generated in normal life.

When forming a fiber deposit by the electrostatic spray method, the thickness of the fiber is preferably 10 nm or more, more preferably 50 nm or more when expressed in terms of the diameter equivalent to a circle. Further, it is preferably 5000 nm or less, and more preferably 3000 nm or less. The thickness of the fiber is determined by observing the fiber at a magnification of 10,000 times, for example, by observing with a scanning electron microscope (SEM), and removing defects (fiber mass, fiber intersection, droplet) from the two-dimensional image. It can be measured by arbitrarily selecting 10 fibers, drawing a line orthogonal to the longitudinal direction of the fibers, and directly reading the fiber diameter.

The fiber is a continuous fiber having an infinite length in principle of production, but it is preferable that the fiber has a length of at least 100 times the thickness of the fiber. In the present specification, a fiber having a length of 100 times or more the thickness of the fiber is defined as a "continuous fiber". The coating produced by the electrostatic spray method is preferably a porous discontinuous coating made of a deposit of continuous fibers. Not only can the coating film in this form be treated as a single sheet as an aggregate, but it also has a very soft characteristic, and even if shearing force is applied to it, it does not easily fall apart, making it easier to follow the movement of the body. It has the advantage of being excellent. It also has the advantage of being excellent in the ability to dissipate sweat generated from the skin. Further, there is an advantage that the film can be easily peeled off. On the other hand, the continuous coating having no pores is not easy to peel off, and the sweat wicking property is very low, so that the skin tends to get stuffy.

The fibrous spray composition reaches the skin in a charged state. As mentioned earlier, the skin is also charged, so the fibers adhere to the skin due to electrostatic force. Since fine irregularities such as texture are formed on the surface of the skin, the fibers are more closely adhered to the surface of the skin in combination with the anchor effect due to the irregularities. When the electrostatic spray is completed in this way, the power of 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 adhesion of the coating film is further developed.

The above description has been given to a porous film composed of a deposit of fibers as a film, but the form of the film is not limited to this, and a continuous film having no pores may be formed, and the fiber may be formed. A porous coating having a morphology other than the deposit, for example, a porous coating in which a plurality of through holes are irregularly or regularly formed in a continuous coating, that is, a discontinuous coating may be formed. As described above, a film having an arbitrary shape can be formed by controlling the viscosity of the spray composition, the distance between the nozzle and the skin, the voltage applied to the nozzle, and the like.

The distance between the nozzle and the skin depends on the voltage applied to the nozzle, but is preferably 30 mm or more, and more preferably 50 mm or more, from the viewpoint of uniformly forming the coating film. Further, it is preferably 300 mm or less, and more preferably 150 mm or less. For example, the distance between the nozzle and the skin is preferably 30 mm or more and 300 mm or less, and more preferably 50 mm or more and 150 mm or less. The distance between the nozzle and the skin can be measured by a commonly used non-contact sensor or the like.

Regardless of whether the film formed by the electrostatic spray method is porous or not, the basis weight of the film is preferably 0.1 g / m ² or more, and 1 g / m ² or more. Is more preferable. Further, it is preferably 30 g / m ² or less, and more preferably 20 g / m ² or less. For example, the basis weight of the coating film is preferably 0.1 g / m ² or more and 30 g / m ² or less, and more preferably 1 g / m ² or more and 20 g / m ² or less. By setting the basis weight of the coating in this way, 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 is to electrostatically spray the skin or the skin to which the external agent (A) is applied (also simply referred to as skin). , Means the process of forming a film. The step of electrostatically spraying the composition to a place other than the skin to prepare a sheet made of fibers and applying the sheet to the skin is different from the electrostatic spraying step.

In the present invention, it is selected from water, a polyol and a liquid oil at 20 ° C. before or after the electrostatic spraying step of forming a coating by the electrostatic spraying described above, or before and after the electrostatic spraying step. It is also possible to carry out a liquid agent application step of applying a liquid agent containing one kind or two or more kinds to the skin. By performing the liquid agent application step after the electrostatic spraying step, especially immediately after the electrostatic spraying step, the film formed in the electrostatic spraying step becomes more compatible with the skin with the liquid agent, and the film adheres to the skin highly. The transparency is further improved. Steps are less likely to occur between the edges of the coating and the skin, which also improves the adhesion between the coating and the skin. As a result, even if a film is formed on a part of the skin such as a joint where the degree of expansion and contraction is large or a part having a large curvature such as a shoulder, the peeling or tearing is less likely to occur, and the transdermal absorbability of the medicinal component is obtained. Also improves. Further, when the coating film is transparent, colored transparent, or translucent, the underlying skin is less likely to be concealed. Preferably, when the coating film is a porous coating film composed of a deposit of fibers, the adhesion to the skin is high despite the high porosity, and a large capillary force is likely to be generated. Further, when the fiber is fine, it becomes easy to increase the specific surface area of the porous film, and the transdermal absorbability of the medicinal ingredient is also improved.

Although the present invention has been described above based on the preferred embodiment thereof, the present invention is not limited to the above embodiment. For example, in the above embodiment, a person who wants to form a film on his / her skin grips the electrostatic spray device 10 and generates an electric field between the nozzle of the device 10 and his / her skin. As long as an electric field is generated in the skin, it is not necessary for a person who wants to form a film on his / her skin to hold the electrostatic spray device 10.

With respect to the embodiments described above, the present invention further discloses the following external medicines.
<1> An external preparation comprising a combination of (A) an external preparation containing a medicinal ingredient that can be administered transdermally and (B) a composition containing the component (a) and the component (b). An external medicine, which is used by directly electrostatically spraying the composition (B) onto the skin before or after applying the (A) to the skin to form a film.
(A) One or more volatile substances selected from water, alcohol and ketones,
(B) A polymer having a film-forming ability.

<2> The external medicine according to <1>, which forms a film composed of a deposit of fibers on the skin by electrostatically spraying directly onto the skin.
<3> The electrostatic spraying step is a step of electrostatically spraying the composition onto the skin using an electrostatic spraying device to form a film composed of fiber deposits.
The electrostatic spray device has a container for accommodating 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 to the nozzle. The external medicine according to <1> or <2>, which comprises a power source to which the above-mentioned <1> or <2> is applied.
<4> The medicinal ingredients are α-adrenaline receptor blocker, adrenaline receptor stimulant, angiotensin II receptor antagonist, angiotensin converting enzyme inhibitor, calcium antagonist, steroidal anti-inflammatory / anti-inflammatory analgesic, Parkinson's disease treatment. Drugs, vitamin-related drugs, hormone drugs, sickness / tasting drugs (antifungal drugs), antipyretic analgesics, external hemorrhoids, coronary vasodilators, bronchial dilation / antitussives, cardiotonics, angina treatments, topical Anesthesia, hypoglycemic, oropharyngeal, psychiatric, antiallergic, antihistamine, antibacterial, anti-insect / anti-insect / pesticide, anti-arrhythmic, anti-vomiting, hyperlipidemia, sterilization Drugs, hemostatics, women's drugs, disinfectants, sleeping pills, tissue respiration activators, antipruritic and anti-inflammatory drugs, isotonic solutions, skin disease remedies, non-steroidal anti-inflammatory / anti-inflammatory analgesics, moisturizers, erectile dysfunction remedies, The above-mentioned <1> to <3>, which is one or more selected from an anesthetic, a peripheral vasodilator, an immunosuppressant, a hair drug, a diuretic, an enema, and a quitting aid. External medicine.
<5> The medicinal ingredients are adrenaline receptor stimulants, steroidal anti-inflammatory / anti-inflammatory analgesics, vitamin-related drugs, external hemorrhoids, bronchial dilatation / antitussives, local anesthetics, oropharyngeal drugs, antipsychotics, anti-psychiatric drugs. Allergic drugs, anti-histamine drugs, antibacterial drugs, anti-insect / anti-insect / pesticides, bactericidal drugs, hemostatic drugs, women's drugs, antiseptic drugs, tissue breathing activators, antipruritic and anti-inflammatory drugs, isotonic solutions, skin disease remedies, non- The external drug according to any one of <1> to <3>, which is one or more selected from steroid-based anti-inflammatory / anti-inflammatory analgesics, moisturizers, anesthetics, immunosuppressants, and hair drugs.
<6> The content of the medicinal component in the external preparation (A) is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, further preferably 0.01% by mass or more, and 10% by mass. % Or less is preferable, 20% by mass or less is more preferable, and 30% by mass or less is further preferable. The external preparation according to any one of <1> to <5>.
<7> The external medicine according to any one of <1> to <6>, wherein the dosage form of the external preparation (A) is selected from an ointment, a cream, a gel, a liquid, a lotion, and a tic.

<8> The volatile substance of the 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, and more preferably 0. The external medicine according to any one of <1> to <7> above, which is 67 kPa or more and 40.00 kPa or less, and more preferably 1.33 kPa or more and 40.00 kPa or less.
<9> Among the volatile substances of the component (a), a monohydric chain-type aliphatic alcohol, a monovalent ring-type aliphatic alcohol, and a monovalent aromatic alcohol are used as the alcohol, and the alcohol is used as the alcohol. , Ethanol, isopropyl alcohol, butyl alcohol, phenylethyl alcohol, propanol, pentanol, etc., and one or more of these alcohols are used, any one of the above <1> to <8>. External medicine described in.
<10> Among the volatile substances of the component (a), acetone, methyl ethyl ketone, methyl isobutyl ketone and the like are used as the ketone, and one of these ketones is used alone or in combination of two or more. The method for producing a coating film according to any one of <1> to <9>.
<11> The volatile substance of the component (a) is one or more selected from ethanol, isopropyl alcohol, butyl alcohol, and water, and preferably one or two selected from ethanol and butyl alcohol. The external preparation according to any one of <1> to <10> above, which is more than a species and most preferably ethanol.

<12> Polymers with film-forming ability are water-soluble and are water-soluble.
The water-soluble polymer having a film-forming ability is purulan, hyaluronic acid, chondroitin sulfate, poly-γ-glutamic acid, modified corn starch, β-glucan, glucooligosaccharide, heparin, mucopolysaccharide such as keratosulfate, cellulose, pectin, and the like. Xylan, lignin, glucomannan, galacturonic acid, psyllium seed gum, tamarind seed gum, arabic gum, tragant gum, soybean water-soluble polysaccharide, alginic acid, carrageenan, laminaran, agarose, fucoidan, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose Natural polymers such as, 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. Is the external preparation according to any one of <1> to <11>, which is used alone or in combination of two or more.
<13> Polymers with film-forming ability are water-insoluble and are water-insoluble.
The water-insoluble polymer having a film-forming ability is a completely saponified polyvinyl alcohol that can be insolubilized after film formation, a partially saponified polyvinyl alcohol that can be cross-linked after film formation when used in combination with a cross-linking agent, and poly (N-propanoylethyleneimine). ) Oxazoline-modified silicone such as graft-dimethylsiloxane / γ-aminopropylmethylsiloxane copolymer, polyvinylacetal diethylaminoacetate, zein (main component of corn protein), polyester, polylactic acid (PLA), polyacrylonitrile resin, polymethacrylic acid Acrylic resin such as resin, polystyrene resin, polyvinyl butyral resin, polyethylene terephthalate resin, polybutylene terephthalate resin, polyurethane resin, polyamide resin, polyimide resin, polyamideimide resin, and these water-insoluble polymers may be used alone or in combination of two or more. The external preparation according to any one of <1> to <12>, which is used in combination.
<14> The content of the 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. Hereinafter, it is 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, and further preferably 60% by mass or more and 94% by mass or less. -The external medicine according to any one of <13>.
<15> The content of the 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. Hereinafter, it is 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, and further preferably 6% by mass or more and 40% by mass or less. -The external medicine according to any one of <14>.

<16> The viscosity of the composition is 1 mPa · s or more, preferably 10 mPa · s or more, more preferably 50 mPa · s or more at 25 ° C., and 5000 mPa · s or less, 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, and further preferably 50 mPa · s or more and 1500 mPa · s or less. The external medicine according to any one of <1> to <15>.
<17> The composition contains only the component (a) and the component (b), or contains other components in addition to the component (a) and the component (b).
As the other components, (b) a polymer plasticizer having a film-forming ability, a coloring pigment, an extender pigment, a dye, a surfactant, a UV protective agent, a fragrance, a repellent, an antioxidant, a stabilizer, and a preservative. , The external medicine according to any one of <1> to <16>, wherein various vitamins are used.
<18> When the composition contains other components, the blending 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. The external medicine according to <17>, which is more preferably as follows.
<19> Perform the electrostatic spray method using an electrostatic spray device.
The electrostatic spray device is equipped with a nozzle.
The nozzle is made of various conductors such as metal or non-conductors such as plastic, rubber, and ceramic, and has a shape capable of ejecting the composition from the tip thereof. 18> The external medicine according to any one of.
<20> Perform the electrostatic spray method using an electrostatic spray device.
The electrostatic spray device includes a nozzle and a housing, and has a nozzle and a housing.
The nozzle is arranged at one end in the longitudinal direction of the housing.
The nozzle is any of the above <1> to <19>, which is arranged in the housing so that the blowing direction of the composition coincides with the vertical direction of the housing and becomes convex toward the skin side. External medicine described in Crab.
<21> The sprayed composition volatilizes a volatile substance as a solvent from droplets to solidify a polymer having a film-forming ability as a solute, and forms fibers while being stretched and deformed by a potential difference. 1> The external medicine according to any one of <20>.
<22> Perform the electrostatic spray method using an electrostatic spray device.
The electrostatic spray device is equipped with a nozzle.
The distance between the nozzle and the skin is preferably 30 mm or more, more preferably 50 mm or more, further preferably 300 mm or less, further preferably 150 mm or less, and 30 mm or more and 300 mm or less. The external medicine according to any one of <1> to <21>, more preferably 50 mm or more and 150 mm or less.
<23> The basis weight of the coating film formed by the electrostatic spray method is preferably 0.1 g / m ² or more, more preferably 1 g / m ² or more, and 30 g / m ² or less. Is more preferable, 20 g / m ² or less is more preferable, 0.1 g / m ² or more and 30 g / m ² or less is preferable, and 1 g / m ² or more and 20 g / m ² or less is further preferable. The external medicine according to any one of <1> to <22>.
<24> A liquid agent containing one or more selected from water, a polyol and a liquid oil at 20 ° C. is applied to the skin before and / or after the electrostatic spraying step of forming a film by electrostatic spraying. The external medicine according to any one of <1> to <23>, which has an application step.
<25> A method for treating a disease by transdermal administration, which comprises the following components (a) and (b) before or after (A) an external preparation containing a medicinal component capable of transdermal administration is applied to the skin. A method comprising direct electrostatic spraying of the composition (B) to be formed onto the skin to form a film.
(A) One or more volatile substances selected from water, alcohol and ketones,
(B) A polymer having a film-forming ability.
<26> (A) A combination of an external preparation containing a medicinal ingredient that can be administered transdermally and a composition containing (B) component (a) and component (b), wherein the external preparation (A) is used. A combination characterized in that the composition (B) is electrostatically sprayed directly onto the skin before or after application to the skin to form a film and used.
(A) One or more volatile substances selected from water, alcohol and ketones,
(B) A polymer having a film-forming ability.
<27> A combination of (A) an external preparation containing a medicinal ingredient that can be administered transdermally and (B) a composition containing the component (a) and the component (b), which is used for producing an external drug. The composition (B) is directly electrostatically sprayed on the skin before or after the application of the external preparation (A) to form a film, and is used for producing an external medicine. use.
(A) One or more volatile substances selected from water, alcohol and ketones,
(B) A polymer having a film-forming ability.

Hereinafter, the present invention will be described in more detail by way of examples. However, the scope of the invention is not limited to such examples. Unless otherwise specified, "%" means "mass%".

[Test 1]
[Example 1]
(1) Preparation of composition for spraying The composition shown in Table 3 was used as the composition for spraying.

(2) Preparation of external preparation (A) The creams and oily ointments shown in Tables 1 and 2 were produced. In the production method, the ingredients were mixed to obtain a cream or an oily ointment.
(Production example of cream)
Ingredients 1 to 6 were heated and dissolved at 70 ° C. On the other hand, the components 7 to 12 are heated and dissolved at 70 ° C., and the components 1 to 6 are put into a heat-melted mixed solution and mixed, and then emulsified at 70 ° C. using a homomixer until the room temperature (25 ° C.) is reached. Slowly cooled to obtain a cream (example of manufacturing oily ointment)
Ingredients 2 to 3 were heated and dissolved at 70 ° C. Then, the mixture was slowly cooled while stirring and mixing to 50 ° C. Ingredient 1 was put into a mixed solution of the above ingredients 2 and 3 and slowly cooled to room temperature (25 ° C.) while stirring and mixing to obtain an oily ointment.

(3) External agent application process A model skin test piece prepared by attaching artificial leather composed of layers of polyurethane, polyethylene terephthalate, etc. to a gel that is close to the hardness of human skin and is mainly made of urethane resin with double-sided tape. An application area of 2 cm × 4 cm was set in the center, and the external preparation was applied as evenly as possible.

(4) Electrostatic spraying process A model skin test piece formed in the step of applying the external preparation (A) of (3) using the electrostatic spraying apparatus 10 having the configuration shown in FIG. 1 and having the appearance shown in FIG. The electrostatic spray method was carried out for about 10 seconds. The conditions of the electrostatic spray method were as shown below.
・ Applied voltage: 10kV
・ Distance between nozzle and skin: Approximately 100 mm
-Discharge rate of spray composition: 5 mL / h
・ Environment: 25 ℃, 30% RH
This electrostatic spray formed a porous coating of fiber deposits on the application area on the surface of the model skin test piece. The basis weight of the coating was about 4 g / m ² , and the thickness of the fibers was 506 nm on average.

[Examples 2 to 10]
Using the external preparation (A) shown in Tables 1 and 2 and the spraying composition shown in Table 3, the external preparation (A) was applied and electrostatically sprayed on the model skin test piece in the same manner as in Example 1.

[Comparative Examples 1 to 10]
Using the electrostatic spray device 10 having the configuration shown in FIG. 1 and having the appearance shown in FIG. 2, electrostatic spray (Table 3) is applied to a metal rotating collector provided with a release paper as a base material layer. It went for 20 seconds. The conditions of the electrostatic spray method were as shown below.
・ Applied voltage: 30kV ・ Distance between nozzle and rotating drum collector: 100mm
-Discharge rate of spray composition: 3 mL / h
・ Environment: 25 ℃, 30% RH
By this electrostatic spray, a porous film made of a deposit of fibers was formed on the surface of the release paper, and the release paper was cut into 2 cm × 4 cm to obtain a sheet. In the same manner as in Example 1, an application area of 2 cm × 4 cm was set in the center of the model skin test piece, the external preparation was applied as uniformly as possible, and then a sheet was attached to the application area. The basis weight of the coating was about 0.4 mg / cm ² , and the thickness of the fibers was 506 nm on average.

[Comparative Examples 11 to 15]
The same electrostatic spray as in Example 1 was applied to the model skin test piece without applying the external preparation (A).

[evaluation]
After applying an external agent to the application area of the test piece, applying an electrostatic spray or a sheet, and letting it stand for about 2 hours, check the condition. The bending operation of folding the test piece 180 ° at the center line of the long side (4 cm) of the application area and then unfolding it is repeated 50 times. The state before and after the electrostatic spray was visually compared, and the adhesion of the porous film was the best (the porous film was sufficiently impregnated with an external agent and was transparent without appearing white to gray). Was set to "5", and the one having no adhesion of the porous film was set to "1", and the adhesion after application was evaluated on a 5-point scale. In addition, the state before and after the bending operation was compared by visual observation, and the one with the best adhesion of the porous film (the porous film adhered without floating even at the creases due to bending, and did not appear white to gray. The transparent state) was set to "5", and the porous film having no adhesion was set to "1", and the adhesion after the bending operation was evaluated on a 5-point scale.
The results are shown in Table 3.

10 Electrostatic spray device 11 Low voltage power supply 12 High voltage power supply 13 Auxiliary electric circuit 14 Micro gear pump 15 Container 16 Nozzle 17 Pipe line 18 Flexible line line 19 Current limiting resistance 20 Housing

Claims (3)

(A) An external drug comprising a combination of an external preparation containing a medicinal ingredient and a polyol that can be administered transdermally and a composition containing (B) component (a) and component (b), wherein the external preparation ( An external medicine characterized in that the composition (B) is directly electrostatically sprayed onto the skin before or after applying A) to form a film composed of a deposit of fibers.
(A) One or more volatile substances selected from water, alcohol and ketone 50% by mass or more,
(B) Water-insoluble polymer having film-forming ability 2% by mass or more and 40% by mass or less. The external medicine according to claim 1, wherein the thickness of the fibers of the coating film composed of the deposits of fibers formed on the skin is 10 nm or more and 5000 nm or less in a diameter equivalent to a circle. The electrostatic spraying step is a step of electrostatically spraying the composition onto the skin using an electrostatic spraying device to form a film composed of fiber deposits.
The electrostatic spray device has a container for accommodating 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 to the nozzle. The external medicine according to claim 1 or 2, which comprises a power source to which the above-mentioned product is applied.

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