JP2001270826A - External medicine for treatment and prevention of dermatopathy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external medicine effective against various skin odor diseases such as underarm odor, body odor and foot odor and containing a nitroimidazole compound represented by tinidazole having sulfone group. SOLUTION: The objective external medicine for the prevention and treatment of skin odor diseases contains tinidazole of formula (1) (R1 and R2 are each a 1-6C straight or branched-chain lower alkyl which may have substituents; and (n) is an integer of 1-4) as an active component. The compound exhibits prevention and treatment effects on the complications of various skin odor diseases such as armpit odor, body odor and foot odor and other skin diseases even at a low dose compared with the active amount of the single use of known agent for skin disease (e.g. 1/10 to 1/20) when the compound is used as a composite agent formulated with known other skin disease agent such as adrenocortical hormone agent and antimycotic agent and is free from side action of the composite agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to the following formula:

Embedded image (Wherein, R ₁ and R _{2 each} represent a linear or branched optionally substituted lower alkyl group having 1 to 6 carbon atoms;
A single agent containing, as a main component, a nitroimidazole derivative represented by an integer of 4) or a pharmacologically acceptable salt thereof, or in addition to this main component, a known therapeutic substance for skin diseases as an auxiliary component Axillary odor,
The present invention relates to an external preparation characterized by administering an effective amount by external application to at least one of skin odor diseases selected from body odor and foot odor.

[0002]

2. Description of the Related Art It is considered that skin odors such as axillary odor, body odor and foot odor are caused by degradation of components of apocrine sweat secreted from apocrine glands in pores of skin by various resident bacteria. For the treatment of axillary odor, for example, external preparations such as aluminum chloride solution, formalin and alcohol solution are prescribed and used. However, they suppress odor generation by an antiperspirant effect, and their effects are not perfect and are merely symptomatic treatments. Therefore, it is also known that the odor recurs due to re-perspiration, and that after these uses, side effects such as skin irritation, pruritus and redness are high.

[0003] Thus, at present, there is no medicine for treating odors such as axillary odor, body odor and foot odor in the dermatological field.

[0004] Therefore, there is also a method of removing the skin of the armpits by surgical treatment and removing the apocrine gland,
It takes the trouble of surgery, and the surgical scars spread over a wide area after surgery,
Skin and muscle atrophy and keloids may remain. Surgery is economically burdensome, often recurring, and carries risks such as neuropathy due to surgery errors. The labor, scars, side effects, risk of sequelae, etc., due to such surgical treatments have ruled out the utility of this therapy.

It is known that metronidazole can be used as an external preparation for some selected skin diseases (Japanese Patent Application Laid-Open Nos. 10-500700, 2-503004, 1-503).
061). In addition, tinidazole is eczema (eczema), acne (a
cne), rosacea (rosacea), seborrheic eczema (seborhoeic tupe ec)
skin symptoms like zema), moldy tumors (fungating tumou)
rs), skin ulcers (benign cutaneous ulcers) and the like (WO98 / 27960, WO93 / 2081).
7).

[0006] Tinidazole is a more potent and less toxic compound than metronidazole, a chemotherapeutic agent used orally, as a compound 1966.
It was synthesized by Pfizer Inc. in the United States in 1980 and mainly has an anti-trichomonas effect. Therefore, not only infections caused by Trichomonas vaginalis, but also T-cells that have infected the vulva, cervix, urinary system, rectum, etc.
It has been clinically used as a compound having not only an excellent effect on Richomonasvaginalis but also an antibacterial activity against anaerobic bacteria. The mechanism of action is thought to be due to the fact that the nitro group of tinidazole is reduced by microorganisms, and this reduced form causes dysfunction such as double-strand breaks in the DNA of microorganisms, thereby controlling the division and growth of microorganisms. I have. Therefore,
Tinidazole is a less toxic compound while having a strong bactericidal action.

However, there is no report suggesting that metronidazole or tinidazole is used for the treatment or prevention of skin diseases, especially skin odor abnormality, and that it is useful.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to provide an external preparation having a novel application of a drug represented by tinidazole having a sulfone group among nitroimidazole compounds, and its composition and blending amount. It is an object of the present invention to provide an external preparation having a better therapeutic / preventive effect on skin diseases, particularly odor diseases on the skin, and further having no side effects by selecting a preparation or the like.

[0009]

According to the present invention, it has been found that an external preparation of the compound represented by the formula (1) is effective for treating and preventing skin diseases, especially skin odor diseases such as axillary odor, body odor and foot odor. Furthermore, the present invention provides not only a skin odor disease such as axillary odor but also a compound containing the compound represented by the formula (1) and other known skin disease drugs such as corticosteroids and antifungals. For skin suffering from complications in combination with other skin diseases, even if the amount is smaller than the effective amount of a known skin disease drug as a single agent (for example, 10 to 20 times less), It has been found that it has a therapeutic and preventive effect on skin odor diseases such as axillary odor, body odor, foot odor and the like at the same time as a therapeutic effect on the combined skin disease, and that no side effect due to the complex is observed.

Therefore, the present invention provides the following formula:

Embedded image (Wherein, R ₁ and R _{2 each} represent a linear or branched optionally substituted lower alkyl group having 1 to 6 carbon atoms;
Or a pharmacologically acceptable salt thereof as a main ingredient, or a complex containing as an auxiliary ingredient a known skin disease drug as an auxiliary ingredient in addition to this main ingredient. A therapeutic or prophylactic agent for skin odor diseases such as axillary odor, body odor and foot odor.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The main component of the present invention is an imidazole derivative represented by the formula (1) or a pharmacologically acceptable salt thereof. In the formula, R ₁ represents a linear or branched lower alkyl group having 1 to 6 carbon atoms which may be substituted,
₂ represents a linear or branched lower alkyl group having 1 to 6 carbon atoms, and n represents an integer of 1 to 4.

In the present invention, the optionally substituted straight-chain or branched lower alkyl group having 1 to 6 carbon atoms represented by R ₁ and R ₂ includes, for example, methyl, ethyl, n-propyl And lower alkyl groups such as isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and isohexyl. Among them, as a main component of the present invention, a compound (tinidazole) in which R ₁ is an ethyl group, R ₂ is a methyl group, and n is an integer of 2
Particularly preferred. Further, the substituent is a halogen atom, a cyano group, a carboxyl group which may be protected,
A hydroxyl group which may be protected, an amino group which may be protected, an alkylamino group which may be protected, an alkyl group, an alkoxy group, an alkoxycarbonyl group, an aryl group, a cycloalkyl group, an alkenyl group and a halogen atom And an alkyl group substituted with The protecting group includes all groups that can be used as protecting groups for each carboxyl group, hydroxyl group, amino group, and alkylamino group.

Examples of the pharmacologically acceptable salt of the compound represented by the above formula (1) include an inorganic acid salt and an organic acid salt, and a case where the hydroxyl group has another protecting group is also included in the present invention. . Examples thereof include inorganic acids such as hydrohalic acid, hydrochloric acid, nitric acid, sulfuric acid, and phosphoric acid, and organic acids such as acetic acid, propanoic acid, benzoic acid, citric acid, lactic acid, and butyric acid, and salts thereof.

(Single agent external preparation as main component) One aspect of the present invention is a single agent external preparation containing a compound of the formula (1) or a pharmacologically acceptable salt thereof as a main component. The amount of the main component is 0.01 to 2 with respect to the weight of the external preparation.
0% by weight, preferably 0.1 to 20% by weight, more preferably 1.5 to 10% by weight, particularly preferably 1.5 to 5% by weight. This compounding amount is based on the therapeutic, preventive and ameliorating effects of skin diseases that tinidazole has, taking into account the release of the drug from each of the preparations, and by mixing the above amount with respect to the total weight of the external preparation, It is determined when the intended pharmacological effect is sufficiently recognized.

(Pharmaceutical pH) In the external preparation of the present invention, the compound of the formula (1) to be applied to the skin and compounded in the above amount is melted, dissolved, dispersed and compounded in the external preparation. To do so, it is necessary that the pH of the preparation is in the range of 2.0 to 9.0, more preferably in the range of 4.0 to 7.5. As the pH adjuster, an acid such as hydrochloric acid, citric acid, or lactic acid, or an alkali such as sodium hydroxide, potassium hydroxide, or triethanolamine may be appropriately blended.

If the pH of the preparation is lower than 2.0, the external preparation itself becomes unstable, and the skin cells may be damaged, which is not preferable. Also,
If the pH of the preparation is higher than 9.0, the skin may be damaged or irritating action may occur, which is not preferable.

(Composite external preparation containing auxiliary components) Another embodiment of the present invention is a composite external preparation containing auxiliary components in addition to the main components. When used as a combination, the compounding amount of the compound of the formula (1), which is the main drug, and the pharmacologically acceptable salt thereof may be substantially the same as in the case of a single agent. 0.1-20% by weight, preferably 1-5% by weight
And more preferably 1.5 to 3% by weight.

(Types of Auxiliary Components) The auxiliary components of the present invention include:
Antifungals, corticosteroids, antibacterials, or sulfa drugs, antihistamines, antiallergic agents, antiinflammatory agents, antibiotics, local anesthetics, antivirals, antimetabolites, hair agents, tissue repair promoters, etc. It is a therapeutic agent for known skin diseases, and can contain at least one of the above drug components.

(Blending Amount of Auxiliary Component) The blending amount of the auxiliary component varies depending on the type, the drug, etc., and on the basis of the side effects and pharmacological findings of the pharmacological effect. The amount is selected from the following compounding amounts, each of which is smaller than the amount, and is individually compounded. The amount of the antifungal agent is 0.0005 to 2% by weight, preferably 0.01 to 0.5% by weight based on the weight of the preparation, and the amount of the corticosteroid is 0.001 to 2% by weight based on the weight of the preparation. 1% by weight, preferably 0.001 to 0.1% by weight, and the compounding amount of the antibacterial agent is 0.001 to 5% by weight, preferably 0.01 to 0.5% by weight, based on the weight of the preparation. The compounding amount is 0.001 to 5% by weight, preferably 0.1% by weight of the preparation weight.
0.01 to 0.5% by weight, and the compounding amount of the antihistamine is 0.001 to 10% by weight, preferably 0.01% by weight of the formulation weight.
To 5% by weight, and the compounding amount of the antiallergic agent is 0.001 to 5% by weight, preferably 0.01 to 0.
5% by weight, and the compounding amount of the anti-inflammatory agent is 0.00% of the formulation weight.
1 to 5% by weight, preferably 0.005 to 0.5% by weight,
The amount of the antibiotic is 0.0001 to 5% by weight, preferably 0.001 to 0.1% by weight of the preparation, and the amount of the local anesthetic is 0.001 to 5% by weight of the preparation, preferably Is 0.01 to 1% by weight, and the compounding amount of the antiviral agent is 0.01 to 5% by weight, preferably 0.1 to 1% by weight of the preparation weight.
% By weight, the amount of the antimetabolite is 0.01 to 5% by weight of the preparation.
% By weight, preferably 0.01 to 0.5% by weight, the amount of the hair agent is 0.01 to 10% by weight, preferably 0.1 to 2% by weight of the formulation weight, and the amount of the tissue repair promoter Is 0.1
-20% by weight, preferably 0.1-5% by weight. The amount of the immunosuppressant is 0.001 to 0.1% by weight, preferably 0.0
1 to 0.1% by weight. Vitamin D3 class is 0.0
0001-0.01% by weight, preferably 0.0001-
0.01% by weight.

(PH of Composite Agent) The composite external preparation of the present invention comprises:
It is necessary that the pH is in the range of 3-9, preferably 4-8. The expression of skin irritation varies depending on the human. However, when the pH is 4 or less or the pH is 8 or more, patients suffering from skin diseases are generally assumed to be damaged in the skin tissue and to have a reduced function of the skin tissue. It is not preferable because skin irritation and the like may occur.

(Antifungal agent) Antifungal agents include, for example, croconazole hydrochloride, neticonazole hydrochloride, clotrimazole, ketoconazole, isoconazole nitrate, econazole nitrate, oxyconazole nitrate, sulconazole nitrate, miconazole nitrate, thioconazole, bifonazole, lanconazole and the like. Any antibacterial agents such as imidazole compounds, amorolfine hydrochloride, terbinafine hydrochloride, butenafine hydrochloride, ciclopirox olamine, tolcyclate, tolnaftate, and the like, or derivatives thereof may be used.

(Corticosteroids) Examples of corticosteroids include amcinonide, oxymetholone, potassium canrenoate, prednisolone valerate acetate, diflucortron valerate, dexamethasone valerate, betamethasone valerate, hydrocortisone succinate, and prednisolone succinate. , Chlormadinone acetate, cortisone acetate, diflorazone acetate, hydrocortisone acetate, paramethasone acetate, fludrocortisone acetate, prednisolone acetate, methenolone acetate, difluprednate, betamethasone dipropionate, dexamethasone, triamcinolone, triamcinolone acetonide, halcinonide, hydrocortisone
Flumethasone pivalate, prednisolone farnesylate gel, budesonide, mometasone furoate, fluocinonide, fluocinolone acetonide, fluorometholone, fludoxycortide, prednisolone, alclomethasone propionate, clobetasol propionate, dexamethasone propionate, propionate depropionate, propionate depropionate Corticosteroids (steroids) such as beclomethasone propionate, betamethasone, methylprednisolone, clobetasone butyrate, hydrocortisone butyrate, hydrocortisone butyrate, betamethasone butyrate, sodium hydrocortisone phosphate, betamethasone sodium phosphate, etc., or derivatives thereof )
Should be fine.

(Antibacterial agent) The antibacterial agent is, for example, enoxacin,
Methylrosaniline chloride, ciprofloxacin hydrochloride, lomefloxacin hydrochloride, ofloxacin, sinoxacin, sparfloxacin, tosfloxacin tosylate, nalidixic acid, norfloxacin, pipemidic acid trihydrate, pyrimidic acid, fleroxacin, levofloxacin, etc., or derivatives thereof, etc. Any antibacterial agent may be used.

(Sulfa drug) Sulfa drugs include acetylsulfamethoxazole, salazosulfapyridine, sulfadiazine, silver sulfadiazine, sulfadimethoxine, sulfathiazole, sulfafenazole, sulfamethoxazole, sulfamethoxypyridazine, and sulfamethoxide. Sulfa drug compounds such as pyrazine, sulfamethomidine, sulfamethizole, sulfamerazine, sulfamonomethoxine, sulfisoxazole, sulfisomidine, sodium sulfisomidine, homosulfamine, and derivatives thereof may be used. .

(Antihistamines) Antihistamines include, for example, cyproheptadine hydrochloride, diphenhydramine hydrochloride, triprolidine hydrochloride, hydroxyzine hydrochloride, promethazine hydrochloride, homochlorcyclidine hydrochloride, cimetidine, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline teoculate, and pamoate. Any antihistamine such as hydroxyzine, famotidine, chlorpheniramine maleate, clemastine fumarate, mequitazine, etc., or derivatives thereof may be used.

(Anti-allergic agents) Anti-allergic agents include, for example, astemizole, amlexanox, ibudilast,
Ebastine, azelastine hydrochloride, ebinastine hydrochloride, ozagrel hydrochloride, cetirizine hydrochloride, oxatomide, sodium cromoglycate, seratrodast, tazanolast,
Any antiallergic agent such as terfenadine, suplatast tosylate, tranilast, emedastine fumarate, ketotifen fumarate, pranlukast hydrate, pemirolast potassium, repirinast, or a derivative thereof may be used.

(Anti-inflammatory agent) Anti-inflammatory agents include, for example, actarit, azulene, acemetacin, aspirin, alclofenac, aluminoprofen, ampenac sodium, ampiroxicam, ibuprofen, ibuprofen piconol, indomethacin, indomethacin farnesyl, ufenamate, etodolac, epilizol ,
Emorphazone, tiaramid hydrochloride, tinolizine hydrochloride, buprenorphine hydrochloride, pentazocine hydrochloride, enfenam, oxaprozin, glycyrrhetinic acid, crotamiton, ketoprofen, zaltoprofen, diflunisal, diclofenac sodium, suprofen, sulindac, thiaprofen, tenoxicam, trimethine sodium, nabumeton, naprometonic acid, flumetone , Piroxicam, phenacetin, phenylbutazone, fenoprofen calcium, felbinac, fenbufen,
Bucolome, Bufexamac, Pranoprofen, Flurbiprofen, Floctafenin, Dimethothiazine mesylate, Methiazine, Bendazac, Heparin analog, Progomeratasin maleate, Meclofenam, Mefenamic acid, Loxoprofen sodium, Robenzarit disodium, Vaccinia virus inoculator Any anti-inflammatory agent such as rabbit inflamed skin extract or a derivative thereof may be used.

(Antibiotics) Antibiotics include, for example, acetyl kitasamycin, acetyl spiramycin, amphotillin B, amoxicillin, ampicillin, kanamycin monosulfate, erythromycin ethyl succinate, erythromycin, erythromycin esterate, aclarubicin hydrochloride, oxytetracycline hydrochloride, oxytetracycline hydrochloride Lindamycin, cefetamethopivoxil hydrochloride, cefotiam hexetil hydrochloride, cefcapen pivoxil hydrochloride, cefmenoxime hydrochloride, tarampicillin hydrochloride, tetracycline hydrochloride,
Demethylchlortetracycline hydrochloride, tetracycline hydrochloride, doxycycline hydrochloride, doxorubicin hydrochloride,
Bacampicillin hydrochloride, clindamycin palmitate hydrochloride, vancomycin hydrochloride, pivmecillinam hydrochloride, pleomycin hydrochloride, minocycline hydrochloride, lincomycin hydrochloride, lenampicillin hydrochloride, carbenicillin sodium,
Kitasamycin, potassium clavulanate, clarithromycin, griseofulvin, cloxacin sodium,
Chloramphenicol, colistin sodium methanesulfonate, cycloserine, midecamycin acetate, cyclacillin, dicloxacillin sodium, siccanin,
Josamycin, erythromycin stearate, sulbenicillin sodium, cefaclor, cefazolin,
Cefatridine propylene glycol, cefadroxil, cephapirin, cephamandole sodium, cephalexin, cephalotin sodium, cephalorizine, cefixime, cefoxitin sodium, cefotaxime sodium, cefotetan, cefoperazone sodium, cefditoren pivoxil, cefdinil, cefrosin sodium , Ceftizoxime sodium, ceftibutene, cefteram pivoxil, cefviramide sodium, cefbuperazone sodium, cefpodoxime proxetil, cefmetazole sodium, cefradine, cefloxazine, cefoxime axetil, cefoxime sodium, tical Syrin sodium, tetracycline, sultamicillin tosylate, tobramycin, tricomycin, Nysta , Variotin, chloramphenicol palmitate, piperacillin sodium, pimaricin, faropenem sodium, josamycin propionate, pheneticillin potassium, phenoxymethylpenicillin potassium, benzylpenicillin potassium, benzylpenicillin benzathine, fosfomycin calcium, mitomycin C, midecamycin , Tetracycline metaphosphate, latamoxef sodium, rifampicin, astromycin sulfate, amikacin sulfate, kanamycin sulfate, gentamicin sulfate, sisomicin sulfate,
Dibekacin sulfate, streptomycin sulfate, netilmycin sulfate, fradiomycin sulfate, bleomycin sulfate, bekanamycin sulfate, peplomycin sulfate, polymyxin B sulfate, micronomycin sulfate, ribostamycin sulfate, clindamycin phosphate, roxithromycin, rokitamicin Or an antibiotic compound such as a derivative thereof.

(Local anesthetic) Local anesthetics include, for example, ethyl aminobenzoate, oxybuprocaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethylaminoethyl parabutylaminobenzoate hydrochloride, procaine hydrochloride, mepivacaine hydrochloride, lidocaine hydrochloride, oxesazein, Any local anesthetic compound such as lidocaine or a derivative thereof may be used.

(Antiviral agent) Antiviral agents include, for example,
Acyclovir, ganciclovir, sanilvudine, zalcitabine, didanosine, zidovudine, nevirapine, saquinavir mesylate, nelfinavir mesylate, lamivudine,
Any antiviral agent such as ritonavir, indinavir sulfate or the like, or addition and substitution of a salt thereof may be used.

(Antimetabolites) Examples of antimetabolites include actinomycin D, L-asparaginase, acegraton, ubenimex, uracil, etoposide, enocitabine, aclarubicin hydrochloride, idarubicin hydrochloride, irinotecan hydrochloride, epirubicin hydrochloride, dounorubicin hydrochloride, and hydrochloride Doxorubicin, pirarubicin hydrochloride, fadrozole hydrochloride hydrate, bleomycin hydrochloride, procarbazine hydrochloride, mitoxantrone hydrochloride, carboplatin, carmofur, tamoxifen citrate, toremifene citrate, cyclophosphamide, cisplatin, schizophyllan, cytarabine, cytarabine ocphophosphate, Dinostatin stimamarer, vinorelbine tartrate, sobuzoxane, thiotepa, tegafur, doxyfluridine, docetaxel hydrate, tretinoy , Neocarzinostatin,
Nedaplatin, paclitaxel, bicalutamide, hydroxycarbamide, phosphestrol, busulfan,
Fluorouracil, flutamide, propylthiouracil, pentostatin, porfimer sodium, methyltestosterone, mepithiostan, G-mercaptopurine liposide, mercaptopurine, methotrexate, melphalan, streptococcus extract, pepromycin sulfate, vincristine sulfate, vinblastine sulfate, lentinan, etc. ,
Alternatively, any antimetabolites such as derivatives thereof may be used.

(Agent for Hair) The agent for hair may be any agent for hair such as asnalone, carpronium chloride, minoxidil and the like or derivatives thereof.

(Tissue Repair Promoter) The tissue repair promoter may be, for example, a calf blood extract or the like.

(Immunosuppressant) The immunosuppressant includes cyclosporine, tacrolimus, gliperimus hydrochloride, mizoribine and the like, and derivatives thereof.

(Vitamin D3 Group) The vitamin D3 group includes tacalcitol and the like and derivatives thereof.

(Dosage forms of single agent and composite agent) The dosage forms of the external preparation of the present invention are known and well-known ointments, creams, gels, pastas, gels, shaving creams, foundations, packs, Forms of all external preparations that can be considered dermatologically, such as semisolids such as emulsions, liquids such as lotions, rinses, shampoos, lotions, colons, etc., and solids such as patches and soaps. It is. The dosage form is
The optimal one is selected at any time according to the site and symptoms of the skin disease used. For example, a conventional or known cream or ointment cannot be used for the treatment, prevention and improvement of skin disorders on the head, so that external preparations such as shampoos, gels and rinses are extremely useful.

(Base) As the base of the external preparation of the present invention,
No particular limitation is imposed on the compound of formula (1) or a pharmacologically acceptable salt thereof, or as long as the main agent and the selected auxiliary component can be uniformly melted, blended, and dispersed in the base. . As such a base, an externally-applied base widely used in pharmaceuticals can be used. In addition, although not limited to the following, fats and oils, for example, olive oil, castor oil, etc .; waxes, for example, beeswax, lanolin, jojoba oil, etc .; hydrocarbons, for example, liquid paraffin, vaseline, ceresin, microcrystalline wax Higher fatty acids such as lauric acid, myristic acid, stearic acid and oleic acid; esters such as cetyl lactate, isopropyl myristate and octyldodecyl myristate; higher alcohols such as cetyl alcohol and stearyl alcohol. Surfactants such as glyceryl monostearate, glyceryl monooleate, propylene glycol monostearate, and polyoxyethylene cetyl alcohol if they are nonionic. Ter, etc .; if anionic, sodium cetyl sulfate, sodium stearate, sodium N-acylglutamate, etc .; lower alcohols, such as ethanol, isopropanol, etc .; Bases and the like that can be used in general are listed.

(Supplementary additives) In the external preparation of the present invention, if necessary, antioxidants such as ascorbic acid, tocopherol, citric acid and dibutylhydroxytoluene; preservatives such as dehydroacetic acid and salicylic acid; Methyl paraoxybenzoate, propyl paraoxybenzoate, thymol and the like; humectants such as glycerin,
Lanolin, propylene glycol, 1,3-butylene glycol, urea, sodium hyaluronate and the like; thickeners such as polyethylene glycol, xanthan gum, sodium carboxymethylcellulose and carboxypropylcellulose; buffers and pH adjusters such as citrate Acids such as acid, lactic acid, hydrochloric acid and boric acid, and alkalis such as sodium dihydrogen phosphate, sodium citrate, sodium hydroxide, potassium hydroxide and triethanolamine; excipients such as kaolin and bentonite Known pharmaceutical components used in conventional external preparations can be added.

(Base and Other Compounding Amounts) The compounding amounts of the base and other components in the external preparation are, for example, 0 to 90% by weight of a hydrocarbon, 0 to 90% by weight of a humectant, and 0 to 90% by weight. Surfactant, 0 to 50% by weight thickener, 0 to 80% by weight distilled water, water such as purified water, 0 to 2% by weight preservative, 0 to 5% by weight buffer or pH adjustment Agent, 0.5-
Examples include 20% by weight of higher fatty acid, 0 to 50% by weight of lower alcohol, 0 to 30% by weight of higher alcohol, and trace amounts of fragrances and coloring agents depending on the purpose. These are not limited to these, because they can be changed by an external preparation according to the purpose.

(Pharmaceutical Preparation Method) In preparation of the external preparation of the present invention, it can be prepared according to a conventional preparation method known in pharmacology.

(Supplementary Additives) In addition, the external preparation of the present invention may optionally contain other active ingredients as long as the effect of the external preparation for treating or preventing skin diseases of the present invention is not impaired. . Examples of these medicinal ingredients include known refreshing ingredients, vitamins, exfoliants, cortical depressants, antiseborrheic agents, anti-inflammatory agents, bactericides, antipruritics, and other agents that can be used for skin diseases. Specifically, menthol, vitamins A and B, C, D, E, etc.
Salicylic acid, estradiol, glycyrrhizic acid, benzalkonium chloride, phenol, camphor and the like can be mentioned. In addition, drugs other than the above, for example, narcotics and stimulants such as ethyl morphine hydrochloride, oxycodone hydrochloride,
Cocaine hydrochloride, pethidine hydrochloride, methamphetamine hydrochloride,
dl-methylephedrine hydrochloride, morphine hydrochloride, fentanyl citrate, levallorphan tartrate and the like; topical bactericides such as povidone iodine, iodoform and the like; enzyme preparations such as lysozyme chloride, streptokinase, streptodolase trypsin, deoxyribonuclease; Hepatic extract such as sicon extract, funnel extract, etc .; drugs for hemorrhoids such as killed bacteria of Escherichia coli, epidihydrocholesterin, tribunoside, etc .; dermatologically applicable complex external preparations combining hemostatic agents such as thrombin, cellulose oxide, sodium alginate, etc. It belongs to

(Skin Diseases Confirmed Effectiveness) It was confirmed that the thus prepared external preparation of the present invention was effective in treating and preventing skin odor diseases such as axillary odor, body odor, foot odor and the like.
Furthermore, the combination agent significantly reduced the amount of conventional skin disease treatment agents used in skin disease complication patients suffering from other skin diseases in combination with skin odor diseases such as axillary odor, body odor and foot odor. It was confirmed that the amount used significantly exerted a therapeutic and preventive effect on other skin diseases as well as on skin odor diseases such as axillary odor, body odor and foot odor.

(Form of use of the preparation of the present invention) The external preparation for treating / preventing skin diseases of the present invention supplied as described above can be used, for example, twice to three times a day for the above-mentioned skin diseases.
Apply to skin about once. An external preparation comprising a compound of the formula (1) or a pharmacologically acceptable salt thereof as a single agent is effective in treating various skin odor diseases such as axillary odor, body odor and foot odor. There are no side effects such as scars, hardening of the stratum corneum or side effects such as rebound.

The composite agent of the present invention is applied when it is desired to treat a skin complication patient suffering from other skin diseases in combination with skin odor diseases such as axillary odor, body odor and foot odor.
The proper use of the single agent and the composite agent of the present invention is based on the effect of the compound represented by tinidazole on the treatment and prevention of skin odor diseases such as axillary odor, body odor, foot odor, etc., and has a bactericidal action on bacteria and viruses which cannot be covered by tinidazole and the like. Antifungal, corticosteroid, antibacterial, sulfa, antihistamine, antiallergic, antiinflammatory, antibiotics, local anesthetic, antiviral Agents, antimetabolites, hair agents, and tissue repair promoters. For example, if there is a site that is purulent due to the location of skin odor disease such as axillary odor, body odor, foot odor, etc., an external preparation that is a combination of tinidazole and an antibiotic is used. Administer a single external preparation.

The antifungal agents, corticosteroids, antibacterial agents, sulfa agents, antihistamines, antiallergic agents, antiinflammatory agents, antibiotics, local anesthetics, antiviral agents, antimetabolite, which are auxiliary components used in the present invention. Agents, hair preparations, and tissue repair accelerators have few side effects in currently marketed preparations or in amounts smaller than pharmacologically conceivable, but skin odor disorders such as armpit odor, body odor, and foot odor For effective treatment, armpit odor,
The effect on skin odor diseases such as body odor and foot odor is not known.

The content of the auxiliary component in the external preparation, which is a complex containing the tinidazole or the like of the present invention as a main component and further containing the auxiliary component, is determined by the commercial or pharmacological therapeutic effect of the preparation of each drug. Is insignificant in comparison to the content of the component based on the above. For example, the amount of the antifungal agent and the corticosteroid is 10 to 2 times that of the commercially available one.
Although the effect was about 1/0, the effect was no negative pharmacological effect on skin odor diseases such as axillary odor, body odor and foot odor, and no side effect was observed. Therefore, the present invention is based on tinidazole and the like as a main component, by mixing a small amount of the chemical substance as an auxiliary component, due to the synergistic effect of the two, a better optimal combination agent without side effects, completely novel armpit smell, It succeeded in providing an external preparation for treating and preventing skin odor diseases such as body odor and foot odor.

The external preparation of the present invention is not limited to pharmaceuticals, but also includes quasi-drugs, cosmetics and the like.

[0048]

[Examples and Test Examples] The clinical effects of the external preparation of the present invention on axillary odor, foot odor and body odor will be described in detail below with reference to Examples and Test Examples. It is not limited. In the following examples, as the imidazole derivative of the formula (1) which is a component of the present invention,
Although tinidazole will be described as an example, the same applies to other compounds. In the test, metronidazole was also shown for reference.

[0049]

Examples Example i (Reference): Cream for external use as a single agent Formulation: (a) Active ingredient, 0.5 g of metronidazole
(B) oil phase, 10 g of glycol monostearate, 7 g of cetanol, 9 g of liquid paraffin, white petrolatum 3.5
g, (c) Aqueous phase, 6.5 g of propylene glycol, 1 g of sodium lauryl sulfate, and purified water in a total amount of 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 85 ° C
, The (c) aqueous phase is added to the (b) oil phase, and the component (a) is added with stirring. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting cream in a suitable container.

Example ii: Single cream for external use Formulation: (a) Active ingredient, tinidazole 0.5 g, (b)
Oil phase, glycol monostearate 10 g, cetanol 7 g, liquid paraffin 9 g, white petrolatum 3.5 g,
(C) Aqueous phase, 6.5 g of propylene glycol, 1 g of sodium lauryl sulfate, and purified water in a total amount of 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 85 ° C
, The (c) aqueous phase is added to the (b) oil phase, and the component (a) is added with stirring. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting cream in a suitable container.

Example iii (Reference): Complex external cream formulation Formulation: (a) Active ingredient, 1.5 g of metronidazole, 0.1 g of ketoconazole, (b) Oil phase, 5 g of glycol monostearate, polyoxyethylene (23) 2 g of cetyl ether, 0.5 g of stearic acid, 5 g of cetanol,
3.5 g of white petrolatum, 5 g of liquid paraffin, 5 g of isopropanol myristate, 3 g of octyldodecyl myristate, 0.15 g of propyl paraoxybenzoate,
(C) Aqueous phase, 7 g of propylene glycol, 0.15 g of methyl parahydroxybenzoate, and distilled water in such an amount that the total amount becomes 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 75 ° C
, The (c) aqueous phase is added to the (b) oil phase, and the component (a) is added with stirring. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting cream in a suitable container.

Example iv: Complex external cream Prescription: (a) Active ingredient, tinidazole 1.5 g, ketoconazole 0.1 g, (b) oil phase, glycol monostearate 5 g, polyoxyethylene (23) cetyl ether 2 g 0.5 g of stearic acid, 5 g of cetanol, 3.5 g of white petrolatum, 5 g of liquid paraffin, 5 g of isopropanol myristate, 3 g of octyldodecyl myristate, 0.15 g of propyl paraoxybenzoate, (c)
Aqueous phase, 7 g of propylene glycol, 0.15 g of methyl parahydroxybenzoate, and distilled water in such an amount that the total amount becomes 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 75 ° C
, The (c) aqueous phase is added to the (b) oil phase, and the component (a) is added with stirring. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting cream in a suitable container.

Example v (Reference): Complex cream base Formulation: (a) Active ingredient, metronidazole 3 g, norfloxacin 0.2 g (b) oil phase, stearic acid 5 g, stearyl alcohol 5 g, liquid paraffin 5 g, isopropyl myristate 1 g, span 60 is 1.2 g, thymol 0.2 g, (c) aqueous phase, Tween 60 is 0.7 g,
6 g of propylene glycol, 0. triethanolamine.
4 g, amount of purified water to make 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 75 ° C
, The (c) aqueous phase is added to the (b) oil phase, and the component (a) is added with stirring. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting cream in a suitable container.

Example vi: Complex cream base Formulation: (a) Active ingredient, tinidazole 3g, norfloxacin 0.2g, (b) oil phase, stearic acid 5g, stearyl alcohol 5g, liquid paraffin 5g, isopropyl myristate 1g, 1.2 g of span 60, 0.2 g of thymol, (c) aqueous phase, 0.7 g of Tween 60, 6 g of propylene glycol, 0.4 of triethanolamine
g, amount of purified water to make 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 75 ° C
, The (c) aqueous phase is added to the (b) oil phase, and the component (a) is added with stirring. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting cream in a suitable container.

Example vii (Reference): Complex external ointment Formulation: (a) Active ingredient, metronidazole 2g, diclofenac sodium 0.1g, (b) oil phase, white petrolatum 45g, cetanol 20g, polyoxyethylene hydrogenated castor oil 5g, 2g for Tween 80, crotamiton 3
g, liquid paraffin 5 g, propyl paraoxybenzoate 0.1 g, (c) aqueous phase, methyl paraoxybenzoate 0.1 g.
1 g, amount of distilled water to make total amount 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 85 ° C
, The (c) aqueous phase is added to the (b) oil phase, and the component (a) is added with stirring. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting ointment in a suitable container.

Example viii: Combination external ointment Formulation: (a) Active ingredient, 2 g of tinidazole, 0.1 g of diclofenac sodium, 3 g of crotamiton, (b) Oil phase, 45 g of white petrolatum, 20 g of cetanol, polyoxyethylene hydrogenated castor oil 5 g, 2 g of Tween 80, 3 g of crotamiton, 5 g of liquid paraffin, 0.1 g of propyl parahydroxybenzoate, (c) an aqueous phase, 0.1 g of methyl parahydroxybenzoate, and distilled water to give a total amount of 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 85 ° C
, The (c) aqueous phase is added to the (b) oil phase, and the component (a) is added with stirring. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting ointment in a suitable container.

Example ix (Reference): Cream for external use as a single agent Formulation: (a) Active ingredient, metronidazole 10 g,
(B) oil phase, 7 g of glycol monostearate, 3 g of polyoxyethylene glycol monostearate, 2 g of polyoxyethylene setosteryl ether, 1 g of polyoxyethylene hydrogenated castor oil, 5 g of cetanol, 1 g of beeswax, 3 g of liquid paraffin, (c) Aqueous phase, 5 g of polyethylene glycol, 4 g of 1,3-butylene glycol, and distilled water in a total amount of 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 75 ° C
, And the component (a) is added while stirring the (b) oil phase to the (c) water phase. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting ointment in a suitable container.

Example x: External cream for single agent Formulation: (a) Active ingredient, 10 g of tinidazole, (b) Oil phase, 7 g of glycol monostearate, 3 g of polyoxyethylene glycol monostearate, polyoxyethylene setosteryl ether 2 g, 1 g of polyoxyethylene hydrogenated castor oil, 5 g of cetanol, 1 g of beeswax, 3 g of liquid paraffin, (c) aqueous phase, 5 g of polyethylene glycol, 4 g of 1,3-butylene glycol, and 100 g of distilled water. Production method: (b) oil phase and (c) aqueous phase each at about 75 ° C
, And the component (a) is added while stirring the (b) oil phase to the (c) water phase. Thereafter, it is cooled to a temperature of about 25 ° C. Collect the resulting ointment in a suitable container.

Example xi (Reference): Single lotion Formulation: (a) Active ingredient, metronidazole 5 g, (b)
Oil phase, stearic acid 2 g, cetanol 1.5 g, white petrolatum 4 g, squalane 5 g, tri (caprylic acid / capric acid) glycerin 2 g, sorbitan monooleate 2
g, polyethylene glycol 5 g, (c) aqueous phase, dipropylene glycol 5 g, triethanolamine 0.7
g, purified water 60 g, (d) aqueous phase, isopropanol 10
g, amount of purified water to make 100 g. Production method: (b) oil phase and (c) aqueous phase each at about 70 ° C
, And the component (a) is added while stirring the (b) oil phase to the (c) water phase. Then, after cooling to a temperature of about 40 ° C. with continuous stirring, (d) adding an aqueous phase and cooling to a temperature of about 25 ° C. with stirring. The resulting lotion is collected in a suitable airtight container.

Example xii (Reference): Complex Lotion Formulation: (a) Active ingredient, metronidazole 5 g, tranilast 0.4 g, (b) oil phase, stearic acid 2 g, cetanol 1.5 g, white petrolatum 4 g, squalane 5 g ,
Tri (caprylic / capric acid) glycerin 2g, sorbitan monooleate 2g, polyethylene glycol 5
g, (c) aqueous phase, 5 g of dipropylene glycol, 0.7 g of triethanolamine, 60 g of purified water, (d) aqueous phase,
10 g of isopropanol and 100 g of purified water. Production method: (b) oil phase and (c) aqueous phase each at about 70 ° C
, And the component (a) is added while stirring the (b) oil phase to the (c) water phase. Then, after cooling to a temperature of about 40 ° C. with continuous stirring, (d) adding an aqueous phase and cooling to a temperature of about 25 ° C. with stirring. The resulting lotion is collected in a suitable airtight container.

Example xiii: Complex lotion Formulation: (a) Active ingredient, tinidazole 3 g, clotrimazole 0.1 g, prednisolone acetate 0.005 g,
(B) oil phase, 2 g of stearic acid, 1.5 g of cetanol.
White petrolatum 4 g, squalane 5 g, tri (caprylic acid / capric acid) glycerin 2 g, sorbitan monooleate 2 g, polyethylene glycol 5 g, (c) aqueous phase,
5 g of dipropylene glycol, 0.7 g of triethanolamine, 60 g of purified water, (d) an aqueous phase, 10 g of isopropanol, and a total amount of 100 g of purified water. Production method: (b) oil phase and (c) aqueous phase each at about 70 ° C
, And the component (a) is added while stirring the (b) oil phase to the (c) water phase. Then, after cooling to a temperature of about 40 ° C. with continuous stirring, (d) adding an aqueous phase and cooling to a temperature of about 25 ° C. with stirring. The resulting lotion is collected in a suitable airtight container.

Example xiv: Complex Gel Formulation: (a) Active ingredient, tinidazole 3 g, diphenhydramine hydrochloride 0.2 g, betamethasone 0.01 g, carpronium chloride 0.2 g, (b) oil phase, polyoxyethylene oleyl alcohol ether 1 g, (c) aqueous phase, 6 g of polyethylene glycol 1500, 2 g of polyoxyethylene glycol 400, 0.2 g of sodium EDTA, (d) aqueous phase, 8 g of dipropylene glycol,
(E) 0.1 g of aqueous phase, potassium hydroxide, (f) aqueous phase, 0.5 g of carboxyvinyl polymer, 0.2 g of methylcellulose, and purified water in a total amount of 100 g.

Production method: (f) After the aqueous phase is uniformly dissolved, (c) the aqueous phase is added, the component (a) is added, and the mixture is heated, dissolved and dispersed. To this is added (d) an aqueous phase, (b) an oil phase, and a mixture obtained by heating and melting at a temperature of about 60 ° C. While stirring, the aqueous phase is neutralized by adding (e) and cooled to a temperature of about 25 ° C. The resulting gel is collected in a suitable container.

Example xv: Complex external cream formulation: (a) Active ingredient, tinidazole 2 g, chloramphenicol 0.001 g, hydrocortisone acetate 0.0
01 g, (b) oil phase, glycol monostearate 8
g, 7 g of cetanol, 10 g of liquid paraffin, 3.5 g of white petrolatum, (c) aqueous phase, propylene glycol 6.
5 g, 0.8 g of sodium lauryl sulfate and 100 g of purified water in total.

Production method: (b) The oil phase and (c) the aqueous phase are each maintained at a temperature of about 85 ° C., and (c) the aqueous phase is added to (b) the oil phase and the component (a) is added with stirring. . Then, about 2
Cool to a temperature of 5 ° C. Collect the resulting cream in a suitable container.

[0066]

[Test Example] Test Example i: Clinical Test Example The external preparation of the present invention was applied to a patient suffering from actual skin inflammation and axillary odor, and the therapeutic effect thereof was examined.

The following patients were applied as target patients. Subject A (right): right arm side of a 33-year-old man suffering from armpit odor Subject A (left): left arm side of a 33-year-old man suffering armpit odor

Method: Subject A (right): external cream of Example i (Reference Example) Subject A (left): external cream of Example ii The above-mentioned topical cream suffering from axillary odor Were applied twice a day, and the progress was observed.

[0069]

[Table 1]

As described above, the axillary odor of each of the subjects A was reduced after 7 to 14 days on both the right and left sides, and 14 to 2 days later.
One day later he was completely cured. In addition, there was no irritation or abnormality on the skin of the subject A at the time of application.

Test Example ii: Clinical Test Example An external preparation of the present invention was applied to a patient suffering from actual skin inflammation and axillary odor, and the therapeutic effect thereof was examined.

The following patients were applied as target patients. Subject B (right): right arm side of a 27-year-old man suffering from axillary odor Subject B (left): left arm side of a 27-year-old man suffering from axillary odor Subject C (right): axillary odor Subject C (left): Left arm of a 44-year-old man suffering from axillary odor Subject D (Right): Age 23-year-old suffering from axillary odor Right arm side of a female Subject D (left): Left arm side of a 23-year-old female suffering from armpit odor

Method: Subject B (right): Topical cream of Example iii (Reference Example) Subject B (left): Topical cream of Example iv Subject C (right): Topical cream of Example v Agent (Reference Example) Subject C (left): cream for external use of Example vi Subject D (right): cream for external use of Example vii (reference example) Subject D (left): cream for external use of Example viii Preparations The above-mentioned topical cream was applied twice a day to sites affected by axillary odor, and the progress was observed. The results are shown in Table 2.

[0074]

[Table 2]

As shown in the table, the odor of armpit odor on both the left and right sides of the subjects B, C, and D was reduced after 3 to 5 days, and 7 to 10 days.
After a day, the armpit odor and skin condition improved. In addition, at the time of application, all subjects had no irritation or abnormality on the skin.

The external preparations of Examples ix to xiv also improved the odor for axillary odor in about 3 to 5 days, and 7-1.
On day 0, the results showed that both the odor and the skin condition were improved. Also, lotions and gels were easy to use.

In addition, since it was considered that the axillary odor could be reduced by the effect of the base alone, application was performed twice a day for two consecutive weeks with a placebo, but there was no effect.

Test Example iii: Clinical Test Example The therapeutic effect of an external preparation of the present invention was applied to a patient who had a bad odor on an actual foot.

The following patients were applied as target patients. Subject E (right): Age 24 with odor below ankle
Right foot of an old man (a place where feet are commonly referred to as smelling) Subject E (left): Age 24 with a bad smell below the ankle
Old man of the left foot (commonly location where the foot is said to smell)

Method: Subject E (left): external lotion preparation of Example xii (Reference Example) Subject E (left): external lotion preparation excluding the active ingredient of Example xii Placebo contains active ingredient in right foot When the applied external lotion was applied, the odor of the foot disappeared in about 4 to 5 hours. However, even after the placebo was applied to the left foot, the odor of the foot did not disappear even after about 4 to 5 hours.

Test Example iv: Clinical Test Example The topical cream prepared in Example xv was applied to a 33-year-old man suffering from axillary odor twice a day for 4 consecutive weeks and the progress was observed. did. At the start of the treatment, skin inflammation was confirmed and the state of unpleasant odor was changed to a normal skin state that was almost unchanged after one week compared to healthy people. No longer. Thereafter, observation was made up to 4 weeks, but an extremely healthy skin condition was maintained without side effects or recurrence.

[0082]

As described above, a single agent containing a nitroimidazole derivative represented by the general formula (1) represented by tinidazole, which is an external preparation of the present invention, is used for the treatment, prevention and improvement of axillary odor, foot odor and body odor. It turned out to be very effective for disinfection. In addition, not only for axillary odor, but also for skin with complex complications with other dermatitis, nitroimidazole compound as the main component and antifungals, adjuvant corticosteroids, External preparations, which are combined with at least one of antibacterial, sulfa, antihistamine, antiallergic, anti-inflammatory, antibiotic, antiviral, and antimetabolic agents, have a very wide range of skin odor diseases. It is a useful medicine for complications. From the above results, the external preparation according to the present invention is a wonderful invention in dermatology at present, since there is no drug having a remarkable effect in treating skin odor diseases.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme court ゛ (Reference) A61K 7/021 A61K 7/021 7/075 7/075 7/08 7/08 7/15 7/15 7 / 46 7/46 A 9/06 9/06 9/70 401 9/70 401 A61P 17/00 A61P 17/00 // C07D 233/94 C07D 233/94 F term (reference) 4C076 AA06 AA72 BB31 CC18 DD05F DD34A DD37A DD38A DD46F 4C083 AA082 AB032 AC012 AC022 AC072 AC092 AC122 AC182 AC242 AC352 AC392 AC422 AC432 AC442 AC472 AC482 AC542 AC692 AC792 AC851 AC852 AD042 AD092 AD262 BB41 CC04 CC05 CC07 CC12 CC17 CC21 CC38 CC39 DD12 DD22 DD18 A31 DD31 DD05 DD01 DD31 DD01 MA22 MA28 MA32 MA63 NA14 ZA89

Claims (12)

[Claims] (1) Formula (1) (Wherein, R ₁ and R _{2 each} represent a linear or branched optionally substituted lower alkyl group having 1 to 6 carbon atoms;
A nitroimidazole derivative or a pharmacologically acceptable salt thereof represented by the formula (1), by external application to at least one of skin odor diseases selected from axillary odor, body odor and foot odor. An external preparation characterized by administering an effective amount. 2. The method according to claim 1, wherein the main component is tinidazole (R ₁ = ethyl, R
The external preparation according to claim 1, wherein ₂ = methyl, n = 2). 3. The external preparation according to claim 1, wherein the content of the main component is 0.1 to 20% by weight based on the preparation. 4. The external preparation according to claim 3, wherein the content of the main component is 1.5 to 10% by weight based on the preparation. 5. A complex comprising, as an auxiliary drug, a known therapeutic substance for skin diseases as an auxiliary drug in addition to the main component, wherein the auxiliary component is selected from at least one of the following compounds.
An external preparation according to any one of the above. 1) Antifungal 2) Corticosteroid 3) Antibacterial 4) Sulfa 5) Antihistamine 6) Antiallergic 7) Antiinflammatory 8) Antibiotic 9) Local anesthetic 10) Antiviral 11) Antimetabolites 12) Hair preparation 13) Tissue repair promoter 14) Immunosuppressant 15) Vitamin D3 group 6. The external preparation according to claim 5, wherein the content of the auxiliary component is selected from at least one of the following. 1) Antifungal agent 0.0005 to 2% by weight 2) Corticosteroid agent 0.0001 to 1% by weight 3) Antibacterial agent 0.001 to 5% by weight 4) Sulfa agent 0.001 to 5% by weight 5) Antihistamine 0 0.001 to 10% by weight 6) Antiallergic agent 0.001 to 5% by weight 7) Antiinflammatory agent 0.001 to 5% by weight 8) Antibiotic 0.0001 to 5% by weight 9) Local anesthetic 0.001 to 0.001% 5% by weight 10) 0.01 to 5% by weight of antiviral agent 11) 0.01 to 5% by weight of antimetabolite 12) 0.01 to 10% by weight of hair agent 13) 0.1 to 20 of tissue repair promoter 14) Immunosuppressant 0.001-0.1% by weight 15) Vitamin D3 group 0.00001-0.1% by weight 7. The external preparation according to claim 6, which is administered for skin odor diseases selected from axillary odor, body odor, and foot odor and other complications of skin diseases. 8. The external preparation according to any one of claims 1 to 7, wherein the pH of the preparation is in the range of 2.0 to 9.0. 9. The external preparation according to claim 8, wherein the pH of the preparation is in the range of 3.0 to 9.0. 10. The external preparation according to claim 9, wherein the pH of the preparation is in the range of 4.0 to 9.0. 11. The preparation according to claim 8, wherein the preparation is selected from the following:
10. The external preparation according to any one of 10 above. 1) Ointment 2) Cream 3) Lotion 4) Patch 5) Shampoo 6) Gel 7) Rinse 8) Liquid 9) Soap 10) Lotion 11) Emulsion 12) Pasta 13) Shaving cream 14) Foundation 15) Colon 16) Packing agent 12. The method for producing an external preparation according to any one of claims 1 to 11.