WO2013125440A1 - Veterinary dermatological preparation - Google Patents

Veterinary dermatological preparation Download PDF

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Publication number
WO2013125440A1
WO2013125440A1 PCT/JP2013/053530 JP2013053530W WO2013125440A1 WO 2013125440 A1 WO2013125440 A1 WO 2013125440A1 JP 2013053530 W JP2013053530 W JP 2013053530W WO 2013125440 A1 WO2013125440 A1 WO 2013125440A1
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WIPO (PCT)
Prior art keywords
animal skin
preparation
skin preparation
surface tension
methyl
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PCT/JP2013/053530
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French (fr)
Japanese (ja)
Inventor
圭佑 窪田
由明 吉岡
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株式会社大阪製薬
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Publication of WO2013125440A1 publication Critical patent/WO2013125440A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A61K9/0017—Non-human animal skin, e.g. pour-on, spot-on
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics

Definitions

  • the present invention is highly safe for companion animals such as dogs, cats, rabbits, and hamsters, and mammals that are domestic animals such as cows, pigs, chickens, and horses.
  • the present invention relates to an animal skin preparation having at least one sex effect.
  • the paste-like preparation for skin is taken out from the container to the human hand and spread onto the outer skin of the mammal by human hand, or the skin preparation is taken out from the container directly to the outer skin of the mammal. It was necessary to spread by human hands.
  • JP-A-10-109928 discloses at least one kind of antibacterial agent, antifungal agent and the like, a fluid oily substance, a polyhydric alcohol and the like, and has a viscosity of 5000 to 50000 cps at 20 ° C.
  • An invention of certain creamy veterinary formulations is described.
  • the bacteria may spread not only to the affected area but also to the surrounding hair, skin, or the entire body, so the paste is not uniform throughout the entire area of the skin. It is necessary to spread the formulation.
  • the paste-like preparation is spread by human hands, there is a problem that the hair gets in the way and the drug cannot be reliably administered to the affected area.
  • the affected area is spread by hand when treating the affected area, at least one of fungi and fungi adhering to the affected area and the surrounding hair may be scattered and spread to places other than the affected area.
  • an object of the present invention is to provide a preparation for skin.
  • the animal skin preparation according to the present invention comprises at least one of an antifungal agent and an antibacterial agent;
  • An animal skin preparation characterized by containing a polar organic solvent and being in a liquid state.
  • the antifungal agent is one or more selected from polyene, triazole, imidazole and allylamine, and the antibacterial agent is penicillin, aminoglycoside, thiostrepton
  • the animal skin preparation according to any one of (1) to (3), wherein the preparation is one or more selected from gluconates, new quinolones, and steroids.
  • the organic solvent having polarity is one or more selected from glycol compounds, benzyl alcohol, and N-methylpyrrolidone. It is a preparation for animal skin described.
  • the present invention due to the above-described action, it is efficiently applied to the outer skin of companion animals such as dogs, cats, rabbits and hamsters and mammals such as cattle, pigs, chickens and horses. It can be used without waste until the end of the user's hands.
  • the animal skin preparation according to the present invention contains at least one of an antifungal agent and an antibacterial agent and an organic solvent having polarity, and is characterized by being liquid.
  • the antifungal agent used in the present invention is a polyene compound, triazole compound, imidazole compound, allylamine compound, or the like, and has the effect of inhibiting fungal growth.
  • Examples of the method for inhibiting fungal growth include mechanisms such as inhibiting fungal cell membrane synthesis, inhibiting cell wall synthesis, and inhibiting the synthesis of various compounds necessary for growth.
  • amphotericin B, nystatin, etc. as polyene compounds, fluconazole, itraconazole, etc. as triazole compounds, miconazole, ketoconazole, miconazole nitrate etc. as imidazole compounds, terbinafine hydrochloride, etc. as allylamine compounds, etc. is preferred.
  • the above antifungal agents can be used alone or in combination of two or more.
  • the content of the antifungal agent is 0.2 to 50% by weight, more preferably 0.3 to 25% by weight, and most preferably 0.5 to 15% by weight. %. If the content of the antifungal agent is within this range, the fungus can be killed.
  • the antibacterial agents used in the present invention are compounds such as penicillins, aminoglycosides, thiostreptons, gluconates, new quinolones, steroids, etc., and have the effect of inhibiting the growth of bacteria.
  • Examples of the method for inhibiting fungal growth include mechanisms for inhibiting fungal cell membrane synthesis, inhibiting cell wall synthesis, and inhibiting the synthesis of various compounds necessary for growth.
  • penicillin compounds include penicillin G, ampicillin, bacampicillin, lenampicillin, cyclacillin, amoxicillin, pibmecillin, aspoxillin, cloxacillin, piperacillin, methicillin, and the like.
  • Gentamicin, fradiomycin, tobramycin, amikacin, arbekacin, astromycin, isepamicin, bekanamycin, dibekacin, micronomycin, netilmycin, paromomycin, ribostamycin, sisomycin, spcutinomycin, etc. as thiostrepton compounds
  • Thiostrepton is a gluconate-based compound such as chlorhexidine.
  • new quinolone-based compounds include ofloxacin, orbifloxacin, norfloxacin, enoxacin, ciprofloxacin hydrochloride, lomefloxacin hydrochloride, levofloxacin, garenoxacin, fleroxacin, sitafloxacin, tosufloxacin tosylate, sparfloxacin, Gatifloxacin, moxifloxacin, and the like are preferable, and the steroid compound is preferably triamcinolone acetonide.
  • the above antibacterial agents can be used alone or in combination of two or more.
  • the content of the antibacterial agent is 0.2 to 50% by weight, more preferably 0.3 to 25% by weight, and most preferably 0.5 to 15% by weight. It is. If the content of the antibacterial drug is within this range, the bacteria can be killed.
  • the organic solvent having a polarity used in the present invention is an organic substance in which a bias of charge occurs in the molecule, is liquid at 20 ° C., dissolves antifungal and antibacterial drugs, and diffuses into the outer skin of animals. Efficacy that is easy to do.
  • the polar organic solvent is classified into a protic organic solvent and an aprotic organic solvent, and any organic solvent can be used.
  • an organic solvent having a polarity with a small surface tension or contact angle can quickly diffuse into the animal skin when the preparation of the present invention is dripped or sprayed onto the animal skin, Antibacterial and antibacterial effects can be exhibited by spreading the antibacterial agent farther than the portion where the antibacterial agent is adhered by dropping or the like. Therefore, it is preferable that the organic solvent having polarity has a small surface tension and contact angle. And even if it is a solvent with a low viscosity, since the surface tension and contact angle are not necessarily small, there is not necessarily a correlation with a viscosity, surface tension, and a contact angle.
  • polar organic solvents include ethanol, ethylene glycol, triethanolamine, propylene glycol, benzyl alcohol, 1,3-butylene glycol, diethylene glycol, diethylene glycol monoethyl ether (ethyl diglycol), diethylene glycol monobutyl ether (butyl dibutyl ether).
  • Aprotic polar solvents which are alcohol compounds such as glycol
  • aprotic polar solvents such as N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, acetonitrile, etc.
  • ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol, or glycol compounds such as monoethyl ether and monobutyl ether, benzyl alcohol, and N-methylpyrrolidone are preferable.
  • the organic solvent which has said polarity can be used only in 1 type, or in combination of 2 or more types.
  • the content ratio of the organic solvent having polarity in the animal skin preparation according to the present invention is not particularly limited.
  • the surface tension in the animal skin preparation according to the present invention is determined as follows. , Preferably at 25 ° C. so as to be adjusted to 50 mN / m or less.
  • a surfactant can be added to the animal skin preparation according to the present invention in order to reduce the surface tension of the preparation.
  • a nonionic surfactant for example, a nonionic surfactant, a cationic surfactant, an anionic surfactant, and an amphoteric surfactant are preferable, and a nonionic surfactant is more preferable.
  • alkyltrimethylammonium salt dialkyldimethylammonium salt, alkylbenzyldimethylammonium salt and the like are preferable.
  • anionic surfactant alkylbenzene sulfonate, alkyl polyoxyethylene sulfate, alkyl sulfate, alkyl phosphate, fatty acid salt and the like are preferable.
  • an anti-inflammatory drug can be added to the animal skin preparation according to the present invention in order to reduce inflammation occurring in the animal skin.
  • Anti-inflammatory drugs are not limited to either natural products or synthetic products, and are steroidal compounds that have the same effect as corticosteroids and other non-steroidal compounds that suppress inflammation caused by various factors. be able to.
  • steroidal compounds that have the same effect as corticosteroids and other non-steroidal compounds that suppress inflammation caused by various factors.
  • triamcinolone acetonide, dexamethasone, prednisone, fludrocortisone, hydrocortisone and the like are preferable as the steroidal compound
  • acetylsalicylic acid, diclofenac, indomethacin, ibuprofen, ketoprofen, naproxen, piroxicam and the like are preferable as the nonsteroidal compound.
  • the above-mentioned anti-inflammatory drugs can be used alone or in combination of two or more, but it is more preferable to use a combination of two.
  • an insecticidal or repellent component and an insect growth inhibitor may be added to the animal skin preparation according to the present invention in order to control and repel insect fleas, mites, and other pests present in the animal skin.
  • Insecticides or repellents include natural pyrethroids, which are active ingredients contained in insecticides, and synthetic pyrethroids, terpineol, eucalyptus oil, lemon oil, and citonella, which are derivatives of pyrethrin, and companions such as dogs, cats, rabbits, and hamsters.
  • the insects such as fleas and ticks that parasitize mammals such as animals, cattle, pigs, chickens, and horses can be comatose or insecticidal.
  • natural pyrethroids include pyrethrin I ⁇ (1R, 3R) -2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (1S) -2-methyl- 4-oxo-3- (2Z) -2,4-pentadienyl-2-cyclopenten-1-yl ester>, pyrethrin II ⁇ (1R, 3R) -3-[(1E) -3-methoxy-2-methyl- 3-oxo-1-propenyl] -2,2-dimethylcyclopropanecarboxylic acid (1S) -2-methyl-4-oxo-3- (2Z) -2,4-pentadienyl-2-cyclopenten-1-yl ester >, Cineline I ⁇ (1R, 3R) -2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (1S) -2-methyl- 4-oxo
  • pyrethroid type compound can be used only in 1 type or in combination of 2 or more types, it is more preferable to use combining 2 types.
  • Insect growth inhibitors are compounds that inhibit the growth of fleas and ticks, such as fleas and ticks, when they adhere to eggs, larvae, or pupa.
  • the mechanism of inhibiting the growth is directly applied to the epidermis for molting. There is no particular limitation such as a mechanism that does not create an epidermis or a mechanism that suppresses growth by antagonizing a compound that promotes growth.
  • insect growth inhibitors include diflubenzuron ⁇ 1- (4-chlorophenyl) -3- (2,6-difluorobenzoyl) urea>, pyriproxyfen ⁇ 1- (4-phenoxyphenoxy) -2- (2- Pyridyloxy) propane>, metoprene ⁇ (2E, 4E) -11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid isopropyl>, etoxazole ⁇ 2- (2,6-difluorophenyl) -4 -[4- (1,1-dimethylethyl) -2-ethoxyphenyl] -4,5-dihydrooxazole>, Novallon ⁇ (RS) -1- [3-chloro-4- (1,1,2-tri Fluoro-2-trifluoromethoxyethoxy) phenyl] -3- (2,6-difluorobenzoyl) urea>,
  • a touching agent such as polyether silicone can be added to give a smooth feel when attached to the skin of a pet.
  • Vitamin C ascorbic acid
  • vitamin E tocophenol
  • BHT dibutylhydroxytoluene
  • BHA butylhydroxyanisole
  • sorbic acid to prevent deterioration due to oxidation of insecticidal ingredients, repellent ingredients, insect growth inhibitors
  • Antioxidants such as potassium sorbate and sodium sulfite can be added.
  • fragrances can be added to give fragrance to l-menthol and the animal skin preparation according to the present invention in order to give a refreshing feeling.
  • the animal skin preparation according to the present invention can be applied to the body surface of an animal and diffused as a pour-on preparation. It can also be applied to and spread on the surface of animals as a spray formulation.
  • the surface tension of the animal skin preparation of the present invention is preferably 50 mN / m or less at 25 ° C., more preferably 10 to 46 mN / m, and most preferably 15 to 41 mN / m. .
  • the surface tension is the Wilhelmy method (plate method), which is calculated from the force acting when the plate member is brought into contact with the liquid surface and pulls up the plate member.
  • the hanging drop method pendant drop method
  • maximum bubble pressure method that is calculated from the maximum pressure when bubbles are continuously generated from a probe (capillary tube) inserted into the liquid.
  • the surface tension in the animal skin preparation of the present invention is determined based on a value measured by the wihelmy method (plate method).
  • the contact angle of the animal skin preparation of the present invention is not particularly limited, and is calculated from the surface tension of the preparation, the surface tension of the animal skin, and the like. And when the surface tension of the said formulation is small, the contact angle will also become small and it means that it will be easy to wet and spread to the outer skin of an animal.
  • Example 1 Dissolve 0.27 g of nystatin in 10 g of 2 wt% aqueous sodium hydroxide, 0.25 g of fradiomycin sulfate and 0.25 g of thiostrepton in 20 g of purified water, and 0.1 g of triamcinolone acetonide in 10 g of ethanol. Thereafter, each solution was mixed with 56.13 g of ethyl diglycol and stirred to obtain an animal skin preparation having a total amount of 100 g.
  • Example 2 Dissolve 0.27 g of nystatin in 10 g of 2 wt% aqueous sodium hydroxide, 0.25 g of fradiomycin sulfate and 0.25 g of thiostrepton in 10 g of purified water, and 0.1 g of triamcinolone acetonide in 26 g of ethanol. Thereafter, each solution was mixed with 53.13 g of benzyl alcohol and stirred to obtain an animal skin preparation having a total amount of 100 g.
  • Example 3 Dissolve 0.27 g of nystatin in 10 g of 2 wt% aqueous sodium hydroxide, 0.25 g of fradiomycin sulfate and 0.25 g of thiostrepton in 20 g of purified water, and 0.1 g of triamcinolone acetonide in 20 g of ethanol. Thereafter, each solution was mixed with 59.13 g of N-methylpyrrolidone and stirred to obtain an animal skin preparation having a total amount of 100 g.
  • Example 5 1.0 g of terbinafine hydrochloride was dissolved in 10 g of ethanol, and then the solution was mixed with 89 g of butyl diglycol and stirred to obtain an animal skin preparation having a total amount of 100 g.
  • Example 6 Miconazole nitrate (2.0 g) was dissolved in propylene glycol (20 g), and then the solution was mixed with ethyl diglycol (78 g) and stirred to obtain an animal skin preparation having a total amount of 100 g.
  • Example 7 1.0 g of terbinafine hydrochloride was dissolved in 10 g of a citrate-phosphate buffer solution having a pH of 3, and then the solution was mixed with 89 g of ethyl diglycol and stirred to obtain an animal skin preparation having a total amount of 100 g.
  • ⁇ Comparative Example 1> 1.0 g of terbinafine hydrochloride was dissolved in 99 g of a citrate-phosphate buffer solution having a pH of 3 to obtain an animal skin preparation having a total amount of 100 g.
  • Table 1 summarizes the compositions of Examples 1 to 7 and Comparative Example 1.
  • compositions having good diffusibility were confirmed by the following method. That is, when 30 ⁇ L of various compositions were dropped on the mouse skin, the extent of the spread was measured after a predetermined time. Those that spread 2 cm or more from the dropping point were evaluated as “good”, and those that spread less than 2 cm were evaluated as “bad” as poor. Since a composition having good diffusibility can be spread over a wide area with a small amount, it can be efficiently applied to the outer skin of animals.
  • Candida albicans ATCC10231 yeast is collected with a platinum loop, suspended in a sterilized physiological saline solution, and a suspension containing about 10 8 cells / mL viable bacteria is prepared. And 10 g of various compositions are dispensed into a sterilized polypropylene tube, 50 ⁇ L of bacterial solution is added thereto, and 50 ⁇ L of sterilized physiological saline with polysorbate 80 added at a ratio of 10% is added so as to be mixed evenly.
  • test specimens Uniformly disperse. These test specimens are stored at 20-25 ° C. in the dark. After 28 days, 1 g is collected from the test composition, dissolved in isopropyl myristate that has been filtered and sterilized, and diluted 10-fold. And it dilutes further 10 times using the sterilized physiological saline solution which added the polysorbate 80 in the ratio of 0.05%. Then, the viable cell count was measured using two flat plates by the agar plate method.
  • the surface tension of various compositions was confirmed by the following method. That is, using a surface tension measuring device (CBVP-3, manufactured by Kyowa Interface Science Co., Ltd.) based on the Wilhelmy method, the surface tension immediately after the plate was brought into contact with various compositions at 25 ° C. was read. It was.
  • CBVP-3 surface tension measuring device
  • Table 2 shows the results of these diffusivities, effects, and surface tension.

Abstract

This veterinary dermatological preparation is characterized by being a liquid and containing the following: at least one antifungal agent and/or antibacterial agent; and a polar organic solvent. Said preparation is further characterized by a surface tension at 25°C of 50 mN/m or less. This makes it possible to provide a liquid veterinary dermatological preparation that: is easy to use not only to treat parts of mammals, namely companion animals such as dogs, cats, rabbits, and hamsters and livestock animals such as cattle, pigs, chickens, and horses, that exhibit fungal and/or bacterial infection but also to prevent such infections; does not scatter said fungi or bacteria when used; does not contaminate the applier's hands; and can be used in its entirety without waste.

Description

動物向け外皮用製剤Animal skin preparation
　本発明は、犬、猫、うさぎ、ハムスターなどのコンパニオンアニマルや牛、豚、鶏、馬などの家畜である哺乳類動物に対して安全性が高く、該動物の外皮に素早く拡がり抗真菌性および抗菌性の少なくとも１つの効果を有する動物向け外皮用製剤に関する。 The present invention is highly safe for companion animals such as dogs, cats, rabbits, and hamsters, and mammals that are domestic animals such as cows, pigs, chickens, and horses. The present invention relates to an animal skin preparation having at least one sex effect.
　従来、犬、猫、うさぎ、ハムスターなどのコンパニオンアニマルや牛、豚、鶏、馬などの家畜である哺乳類動物における細菌・真菌による感染性の皮膚疾患や外耳炎などに対して効力を有する外皮用製剤が種々市販等されているが、いずれも軟膏やクリームなどの半固形状であるペースト状のものである。 Conventionally, it is effective for infectious skin diseases and otitis externa caused by bacteria and fungi in companion animals such as dogs, cats, rabbits and hamsters, and mammals such as cattle, pigs, chickens and horses. Various preparations are commercially available, and all of them are paste-forms such as ointments and creams.
　そのため、使用に際しては、容器から人の手にペースト状の外皮用製剤を取り出し当該哺乳類動物の外皮に人の手によって塗り広げる、若しくは、容器から当該哺乳類動物の外皮に直接外皮用製剤を取り出して人の手によって塗り広げる必要があった。 Therefore, in use, the paste-like preparation for skin is taken out from the container to the human hand and spread onto the outer skin of the mammal by human hand, or the skin preparation is taken out from the container directly to the outer skin of the mammal. It was necessary to spread by human hands.
　例えば、特開平１０－１０９９２８号公報には、抗菌薬、抗真菌薬等の少なくとも１種と、流動性油状物質と、多価アルコール類等を含有し、２０℃での粘度が５０００～５００００ｃｐｓであるクリーム状の動物用製剤の発明が記載されている。 For example, JP-A-10-109928 discloses at least one kind of antibacterial agent, antifungal agent and the like, a fluid oily substance, a polyhydric alcohol and the like, and has a viscosity of 5000 to 50000 cps at 20 ° C. An invention of certain creamy veterinary formulations is described.
　前記の特開平１０－１０９９２８号公報に記載のクリーム状の動物用製剤においても、上述したように動物の外皮に人の手によって、当該製剤を塗り広げる必要がある。 In the creamy animal preparation described in JP-A-10-109928, it is necessary to spread the preparation on the outer skin of the animal by human hands as described above.
　さらに、患部の治療だけでなく予防の観点からすると、菌は患部のみならず周囲の被毛、皮膚または体全体に拡散している場合があるため、外皮の特定部位ではなく全体的に満遍なくペースト状の製剤を塗り広げる必要がある。しかしながら、人の手でペースト状の製剤を塗り広げる際、被毛が邪魔をし薬剤の患部への確実な投与が出来ないという問題があった。また、患部の治療をする際に、人の手によって塗り広げると、患部やその周囲の体毛に付着している真菌および菌の少なくとも１種が飛散し、患部以外の箇所にも広がるおそれがあり、さらには、人にも付着するおそれがあった。 Furthermore, from the viewpoint of prevention as well as treatment of the affected area, the bacteria may spread not only to the affected area but also to the surrounding hair, skin, or the entire body, so the paste is not uniform throughout the entire area of the skin. It is necessary to spread the formulation. However, when the paste-like preparation is spread by human hands, there is a problem that the hair gets in the way and the drug cannot be reliably administered to the affected area. In addition, if the affected area is spread by hand when treating the affected area, at least one of fungi and fungi adhering to the affected area and the surrounding hair may be scattered and spread to places other than the affected area. In addition, there is a risk of adhesion to humans.
　また、動物の外皮に塗り終わった後には手に、その製剤が付着しているため、手を拭く、または、手を洗うなどして残存する当該製剤を除去する手間があった。また、これらペースト状の製剤は、チューブ容器に収容され、搾り出して使用されるため、当該容器内に残存しやすく、最後まで無駄なく使用するには容器を何度も強く搾るか、容器を側面から破って広げて使用するなど非常に手間であった。 Also, after the application to the outer skin of the animal, the preparation was adhered to the hand, so it was troublesome to remove the remaining preparation by wiping the hand or washing the hand. In addition, since these paste-like preparations are contained in tube containers and used after being squeezed out, they tend to remain in the containers, and to be used without waste until the end, the container is squeezed many times or the container is It was very troublesome to break and use it.
　そこで、本発明では、犬、猫、うさぎ、ハムスターなどのコンパニオンアニマルや牛、豚、鶏、馬などの家畜である哺乳類動物に対して、真菌および菌の少なくとも１種に感染した患部の治療だけでなく、その感染を予防するために使用しやすく、使用時にそれら真菌や菌を飛散させることもなく、そして、使用者の手を汚すことなく、最後まで無駄なく使用することができる液状の動物向け外皮用製剤を提供することを目的とする。 Therefore, in the present invention, for the companion animals such as dogs, cats, rabbits, hamsters, and mammals that are domestic animals such as cows, pigs, chickens, horses, etc., only treatment of affected areas infected with at least one of fungi and fungi is possible. Not only is it a liquid animal that is easy to use to prevent its infection, does not disperse those fungi and fungi at the time of use, and can be used without waste until the end of the user's hands An object of the present invention is to provide a preparation for skin.
　（１）すなわち、本発明に係る動物向け外皮用製剤は、抗真菌薬および抗菌薬の少なくとも１種と、
極性を有する有機溶媒と、を含有し、液状であることを特徴とする動物向け外皮用製剤である。 (1) That is, the animal skin preparation according to the present invention comprises at least one of an antifungal agent and an antibacterial agent;
An animal skin preparation characterized by containing a polar organic solvent and being in a liquid state.
　（２）そして、２５℃における表面張力が、５０ｍＮ／ｍ以下であることを特徴とする（１）に記載の動物向け外皮用製剤である。 (2) The animal skin preparation according to (1), wherein the surface tension at 25 ° C. is 50 mN / m or less.
　（３）そして、前記抗真菌薬および前記抗菌薬のうち少なくとも１種を、０．２～５０重量％含有することを特徴とする（１）又は（２）に記載の動物向け外皮用製剤である。 (3) The animal skin preparation according to (1) or (2), wherein 0.2 to 50% by weight of at least one of the antifungal agent and the antibacterial agent is contained. is there.
　（４）そして、前記抗真菌薬が、ポリエン系、トリアゾール系、イミダゾール系、アリルアミン系から選択される１種又は２種以上であり、前記抗菌薬が、ペニシリン系、アミノグリコシド系、チオストレプトン系、グルコン酸塩系、ニューキノロン系、ステロイド系から選択される１種又は２種以上であることを特徴とする（１）から（３）のいずれかに記載の動物向け外皮用製剤である。 (4) And the antifungal agent is one or more selected from polyene, triazole, imidazole and allylamine, and the antibacterial agent is penicillin, aminoglycoside, thiostrepton The animal skin preparation according to any one of (1) to (3), wherein the preparation is one or more selected from gluconates, new quinolones, and steroids.
　（５）前記極性を有する有機溶媒が、グリコール系化合物、ベンジルアルコール、Ｎ－メチルピロリドンから選択される１種又は２種以上であることを特徴とする（１）から（４）のいずれかに記載の動物向け外皮用製剤である。 (5) The organic solvent having polarity is one or more selected from glycol compounds, benzyl alcohol, and N-methylpyrrolidone. It is a preparation for animal skin described.
　このように構成すれば、犬、猫、うさぎ、ハムスターなどのコンパニオンアニマルや牛、豚、鶏、馬などの家畜である哺乳類動物の外皮に拡散し易くなることにより、効率良く当該動物の外皮に塗布することができ、使用者が直接製剤に触れる必要がなくなり、容器の内壁に付着することがほとんどない。 If configured in this way, it can easily spread to the outer skin of companion animals such as dogs, cats, rabbits, hamsters, etc., and mammalian animals such as cattle, pigs, chickens, horses, etc. It can be applied and eliminates the need for the user to touch the formulation directly and hardly sticks to the inner wall of the container.
　本発明によれば、前述した作用により、犬、猫、うさぎ、ハムスターなどのコンパニオンアニマルや牛、豚、鶏、馬などの家畜である哺乳類動物に対して、効率良く当該動物の外皮に塗布することができ、使用者の手を汚すことなく、最後まで無駄なく使用することができる。 According to the present invention, due to the above-described action, it is efficiently applied to the outer skin of companion animals such as dogs, cats, rabbits and hamsters and mammals such as cattle, pigs, chickens and horses. It can be used without waste until the end of the user's hands.
　以下、本発明に係る動物向け外皮用製剤に関する実施形態について詳しく説明する。なお、説明中における範囲を示す表記は、上限と下限を含有するものである。 Hereinafter, embodiments relating to animal skin preparations according to the present invention will be described in detail. In addition, the description which shows the range in description contains an upper limit and a minimum.
　本発明に係る動物向け外皮用製剤は、抗真菌薬および抗菌薬の少なくとも１種と、極性を有する有機溶媒と、を含有し、液状であることを特徴とする。 The animal skin preparation according to the present invention contains at least one of an antifungal agent and an antibacterial agent and an organic solvent having polarity, and is characterized by being liquid.
　本発明において使用される抗真菌薬は、ポリエン系、トリアゾール系、イミダゾール系、アリルアミン系などの化合物であり、真菌の生育を阻害する効能を有する。真菌の生育の阻害方法としては、真菌の細胞膜合成を阻害する、細胞壁合成を阻害する、種々生育に必要な化合物の合成を阻害するなどの機構が挙げられる。 The antifungal agent used in the present invention is a polyene compound, triazole compound, imidazole compound, allylamine compound, or the like, and has the effect of inhibiting fungal growth. Examples of the method for inhibiting fungal growth include mechanisms such as inhibiting fungal cell membrane synthesis, inhibiting cell wall synthesis, and inhibiting the synthesis of various compounds necessary for growth.
　例えば、ポリエン系化合物としては、アムホテリシンＢ、ナイスタチンなどが、トリアゾール系化合物としては、フルコナゾール、イトラコナゾールなどが、イミダゾール系化合物では、ミコナゾール、ケトコナゾール、ミコナゾール硝酸塩などが、アリルアミン系化合物としては、塩酸テルビナフィンなどが好ましい。また、上記の抗真菌薬は１種類のみ、又は２種類以上組み合わせて用いることができる。 For example, amphotericin B, nystatin, etc. as polyene compounds, fluconazole, itraconazole, etc. as triazole compounds, miconazole, ketoconazole, miconazole nitrate etc. as imidazole compounds, terbinafine hydrochloride, etc. as allylamine compounds, etc. Is preferred. In addition, the above antifungal agents can be used alone or in combination of two or more.
　また、本発明に係る動物向け外皮用製剤のうち、抗真菌薬の含有割合は、０．２～５０重量％、さらに好ましくは０．３～２５重量％、もっとも好ましくは０．５～１５重量％である。抗真菌薬の含有割合が、この範囲であれば、真菌を死滅させることができる。 In the animal skin preparation according to the present invention, the content of the antifungal agent is 0.2 to 50% by weight, more preferably 0.3 to 25% by weight, and most preferably 0.5 to 15% by weight. %. If the content of the antifungal agent is within this range, the fungus can be killed.
　本発明において使用される抗菌薬は、ペニシリン系、アミノグリコシド系、チオストレプトン系、グルコン酸塩系、ニューキノロン系、ステロイド系などの化合物であり、菌の生育を阻害する効能を有する。菌の生育の阻害方法としては、菌の細胞膜合成を阻害する、細胞壁合成を阻害する、種々生育に必要な化合物の合成を阻害するなどの機構が挙げられる。 The antibacterial agents used in the present invention are compounds such as penicillins, aminoglycosides, thiostreptons, gluconates, new quinolones, steroids, etc., and have the effect of inhibiting the growth of bacteria. Examples of the method for inhibiting fungal growth include mechanisms for inhibiting fungal cell membrane synthesis, inhibiting cell wall synthesis, and inhibiting the synthesis of various compounds necessary for growth.
　例えば、ペニシリン系化合物としては、ペニシリンＧ、アンピシリン、バカンピシリン、レナンピシリン、シクラシリン、アモキシシリン、ピブメシリン、アスポキシシリン、クロキサシリン、ピペラシリン、メチシリンなどが、アミノグリコシド系化合物としては、カナマイシン、ストレプトマイシン、ネオマイシン（硫酸フラジオマイシン）、ゲンタマイシン、フラジオマイシン、トブラマイシン、アミカシン、アルベカシン、アストロマイシン、イセパマイシン、ベカナマイシン、ジベカシン、ミクロノマイシン、ネチルマイシン、パロモマイシン、リボスタマイシン、シソマイシン、スプクチノマイシンなどが、チオストレプトン系化合物としては、チオストレプトンなどが、グルコン酸塩系化合物としては、クロルヘキシジングルコン酸塩などが、ニューキノロン系化合物としては、オフロキサシン、オルビフロキサシン、ノルフロキサシン、エノキサシン、塩酸シプロフロキサシン、塩酸ロメフロキサシン、レボフロキサシン、ガレノキサシン、フレロキサシン、シタフロキサシン、トスフロキサシントシル酸塩、スパルフロキサシン、ガチフロキサシン、モキシフロキサシンなどが、ステロイド系化合物としては、トリアムシノロンアセトニドなどが好ましい。また、上記の抗菌薬は１種類のみ、又は２種類以上組み合わせて用いることができる。 For example, penicillin compounds include penicillin G, ampicillin, bacampicillin, lenampicillin, cyclacillin, amoxicillin, pibmecillin, aspoxillin, cloxacillin, piperacillin, methicillin, and the like. Gentamicin, fradiomycin, tobramycin, amikacin, arbekacin, astromycin, isepamicin, bekanamycin, dibekacin, micronomycin, netilmycin, paromomycin, ribostamycin, sisomycin, spcutinomycin, etc., as thiostrepton compounds, Thiostrepton is a gluconate-based compound such as chlorhexidine. Examples of new quinolone-based compounds include ofloxacin, orbifloxacin, norfloxacin, enoxacin, ciprofloxacin hydrochloride, lomefloxacin hydrochloride, levofloxacin, garenoxacin, fleroxacin, sitafloxacin, tosufloxacin tosylate, sparfloxacin, Gatifloxacin, moxifloxacin, and the like are preferable, and the steroid compound is preferably triamcinolone acetonide. In addition, the above antibacterial agents can be used alone or in combination of two or more.
　また、本発明に係る動物向け外皮用製剤のうち、抗菌薬の含有割合は、０．２～５０重量％、さらに好ましくは０．３～２５重量％、もっとも好ましくは０．５～１５重量％である。抗菌薬の含有割合が、この範囲であれば、菌を死滅させることができる。 In the animal skin preparation according to the present invention, the content of the antibacterial agent is 0.2 to 50% by weight, more preferably 0.3 to 25% by weight, and most preferably 0.5 to 15% by weight. It is. If the content of the antibacterial drug is within this range, the bacteria can be killed.
　本発明において使用される極性を有する有機溶媒は、分子内で電荷の偏りが生じている有機物で、２０℃において液体であり、抗真菌薬、抗菌薬を溶解させ、かつ、動物の外皮に拡散しやすい効能を有する。また、極性を有する有機溶媒には、プロトン性の有機溶媒と、非プロトン性の有機溶媒に分類されるが、いずれの有機溶媒も使用することができる。 The organic solvent having a polarity used in the present invention is an organic substance in which a bias of charge occurs in the molecule, is liquid at 20 ° C., dissolves antifungal and antibacterial drugs, and diffuses into the outer skin of animals. Efficacy that is easy to do. The polar organic solvent is classified into a protic organic solvent and an aprotic organic solvent, and any organic solvent can be used.
　さらに、表面張力や接触角が小さい極性を有する有機溶媒は、本発明の製剤を動物の外皮に滴下、または、噴霧したときに、その動物の外皮に素早く拡散させ、含有される抗真菌薬や抗菌薬を滴下等により付着した箇所よりもより遠くに広げて抗真菌性や抗菌性の効果を発現することができる。そのため、極性を有する有機溶媒としては、表面張力や接触角が小さいことが好ましい。そして、粘度が低い溶媒であっても、その表面張力や接触角が小さいとは限らないため、粘度と、表面張力及び接触角とには必ずしも相関関係があるわけではない。 Furthermore, an organic solvent having a polarity with a small surface tension or contact angle can quickly diffuse into the animal skin when the preparation of the present invention is dripped or sprayed onto the animal skin, Antibacterial and antibacterial effects can be exhibited by spreading the antibacterial agent farther than the portion where the antibacterial agent is adhered by dropping or the like. Therefore, it is preferable that the organic solvent having polarity has a small surface tension and contact angle. And even if it is a solvent with a low viscosity, since the surface tension and contact angle are not necessarily small, there is not necessarily a correlation with a viscosity, surface tension, and a contact angle.
　例えば、極性を有する有機溶媒としては、エタノール、エチレングリコール、トリエタノールアミン、プロピレングリコール、ベンジルアルコール、１，３－ブチレングリコール、ジエチレングリコール、ジエチレングリコールモノエチルエーテル（エチルジグリコール）、ジエチレングリコールモノブチルエーテル（ブチルジグリコール）などのアルコール化合物であるプロトン性極性溶媒、Ｎ－メチルピロリドン、１，３－ジメチル－２－イミダゾリジノン、ジメチルホルムアミド、ジメチルアセトアミド、ジメチルスルホキシド、アセトニトリル、などの非プロトン性極性溶媒が好ましい。さらに、エチレングリコール、プロピレングリコール、１，３－ブチレングリコール、ジエチレングリコール、又は、これらのモノエチルエーテル、モノブチルエーテルであるグリコール系化合物、ベンジルアルコール、Ｎ－メチルピロリドンが好ましい。また、上記の極性を有する有機溶媒は１種類のみ、又は２種類以上組み合わせて用いることができる。 For example, polar organic solvents include ethanol, ethylene glycol, triethanolamine, propylene glycol, benzyl alcohol, 1,3-butylene glycol, diethylene glycol, diethylene glycol monoethyl ether (ethyl diglycol), diethylene glycol monobutyl ether (butyl dibutyl ether). Aprotic polar solvents which are alcohol compounds such as glycol), and aprotic polar solvents such as N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, acetonitrile, etc. . Further, ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol, or glycol compounds such as monoethyl ether and monobutyl ether, benzyl alcohol, and N-methylpyrrolidone are preferable. Moreover, the organic solvent which has said polarity can be used only in 1 type, or in combination of 2 or more types.
　また、本発明に係る動物向け外皮用製剤のうち、極性を有する有機溶媒の含有割合は、特に限定されるわけではないが、後述するように、本発明の動物向け外皮用製剤における表面張力を、２５℃において、５０ｍＮ／ｍ以下と調整するよう配合されることが好ましい。 Further, the content ratio of the organic solvent having polarity in the animal skin preparation according to the present invention is not particularly limited. However, as described later, the surface tension in the animal skin preparation according to the present invention is determined as follows. , Preferably at 25 ° C. so as to be adjusted to 50 mN / m or less.
　そして、本発明に係る動物向け外皮用製剤に、当該製剤の表面張力を低下させるために、界面活性剤を添加することができる。前記界面活性剤としては、例えば、非イオン系界面活性剤、カチオン系界面活性剤、アニオン系界面活性剤、両性界面活性剤が好ましく、非イオン系界面活性剤がより好ましい。 In addition, a surfactant can be added to the animal skin preparation according to the present invention in order to reduce the surface tension of the preparation. As the surfactant, for example, a nonionic surfactant, a cationic surfactant, an anionic surfactant, and an amphoteric surfactant are preferable, and a nonionic surfactant is more preferable.
　上記の種類の界面活性剤のうち、非イオン系界面活性剤として、モノラウリン酸ポリエチレングリコール（ＨＬＢ＝１３．７）、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステルなどの多価アルコールのアルキルエステル、ポリオキシエチレンステアリルエーテル（エチレンオキサイド平均付加モル数が２０、ＨＬＢ＝８）、ポリオキシエチレンソルビタンオレイルエーテルであるポリソルベート８０（エチレンオキサイド平均付加モル数が２０、ＨＬＢ＝１５）などの多価アルコールのアルキルエーテルや、トレオレイン酸ポリオキシエチレンソルビタン（２０Ｅ．Ｏ．）（エチレンオキサイド平均付加モル数が２０、ＨＬＢ＝１１）、ポリオキシエチレングリセリン脂肪酸エステル、ポリオキシエチレンポリグリセリン脂肪酸エステルなどの多価アルコールのアルキルエステルなどが好ましい。また、カチオン系界面活性剤として、アルキルトリメチルアンモニウム塩、ジアルキルジメチルアンモニウム塩、アルキルベンジルジメチルアンモニウム塩などが好ましい。また、アニオン系界面活性剤として、アルキルベンゼンスルホン酸塩、アルキルポリオキシエチレン硫酸塩、アルキル硫酸塩、アルキルリン酸塩、脂肪酸塩などが好ましい。 Among the above types of surfactants, as nonionic surfactants, polyalkyl alcohol alkyl esters such as polyethylene glycol monolaurate (HLB = 13.7), sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, etc. , Polyoxyethylene stearyl ether (ethylene oxide average addition mole number 20, HLB = 8), polyoxyethylene sorbitan oleyl ether polysorbate 80 (ethylene oxide average addition mole number 20, HLB = 15) and other polyhydric alcohols Alkyl ethers of polyoxyethylene sorbitan (20E.O.) (ethylene oxide average addition mole number is 20, HLB = 11), polyoxyethylene glycerin fatty acid ester, polyoxy And alkyl esters of polyhydric alcohols such as Chi Ren polyglycerol fatty acid esters are preferred. As the cationic surfactant, alkyltrimethylammonium salt, dialkyldimethylammonium salt, alkylbenzyldimethylammonium salt and the like are preferable. Further, as the anionic surfactant, alkylbenzene sulfonate, alkyl polyoxyethylene sulfate, alkyl sulfate, alkyl phosphate, fatty acid salt and the like are preferable.
　そして、本発明に係る動物向け外皮用製剤に、動物の外皮に生じている炎症を鎮めるために、抗炎症薬を添加することもできる。 In addition, an anti-inflammatory drug can be added to the animal skin preparation according to the present invention in order to reduce inflammation occurring in the animal skin.
　抗炎症薬は、天然物、合成物のいずれかに限定されず、副腎皮質ホルモンと同様の効果のあるステロイド系化合物、それ以外の非ステロイド系化合物であり、種々の要因で生じた炎症を抑えることができる。例えば、ステロイド系化合物としては、トリアムシノロンアセトニド、デキサメサゾン、プレドニゾン、フルドロコルチゾン、ヒドロコルチゾンなどが好ましく、非ステロイド系化合物としては、アセチルサリチル酸、ジクロフェナク、インドメタシン、イブプロフェン、ケトプロフェン、ナプロキセン、ピロキシカムなどが好ましい。また、上記の抗炎症薬は１種類のみ、又は２種類以上組み合わせて用いることができるが、２種類を組み合わせて用いることがより好ましい。 Anti-inflammatory drugs are not limited to either natural products or synthetic products, and are steroidal compounds that have the same effect as corticosteroids and other non-steroidal compounds that suppress inflammation caused by various factors. be able to. For example, triamcinolone acetonide, dexamethasone, prednisone, fludrocortisone, hydrocortisone and the like are preferable as the steroidal compound, and acetylsalicylic acid, diclofenac, indomethacin, ibuprofen, ketoprofen, naproxen, piroxicam and the like are preferable as the nonsteroidal compound. In addition, the above-mentioned anti-inflammatory drugs can be used alone or in combination of two or more, but it is more preferable to use a combination of two.
　そして、本発明に係る動物向け外皮用製剤に、動物の外皮に存在するノミ、ダニなどの害虫を駆除や忌避するため、殺虫又は忌避成分、昆虫成長阻害剤を添加することもできる。 In addition, an insecticidal or repellent component and an insect growth inhibitor may be added to the animal skin preparation according to the present invention in order to control and repel insect fleas, mites, and other pests present in the animal skin.
　殺虫又は忌避成分は、除虫菊に含有される有効成分である天然ピレスロイドや、ピレトリンの誘導体である合成ピレスロイド、テルピネオール、ユーカリオイル、レモン油、シトネラ等であり、犬、猫、うさぎ、ハムスターなどのコンパニオンアニマルや牛、豚、鶏、馬などの家畜である哺乳類動物に寄生するノミやダニなどの害虫の成虫に対して、昏睡させ、または、殺虫等することができる。例えば、ピレスロイド系化合物としては、天然ピレスロイドとして、ピレトリンＩ＜（１Ｒ，３Ｒ）－２，２－ジメチル－３－（２－メチル－１－プロペニル）シクロプロパンカルボン酸（１Ｓ）－２－メチル－４－オキソ－３－（２Ｚ）－２，４－ペンタジエニル－２－シクロペンテン－１－イルエステル＞、ピレトリンＩＩ＜（１Ｒ，３Ｒ）－３－［（１Ｅ）－３－メトキシ－２－メチル－３－オキソ－１－プロペニル］－２，２－ジメチルシクロプロパンカルボン酸（１Ｓ）－２－メチル－４－オキソ－３－（２Ｚ）－２，４－ペンタジエニル－２－シクロペンテン－１－イルエステル＞、シネリンＩ＜（１Ｒ，３Ｒ）－２，２－ジメチル－３－（２－メチル－１－プロペニル）シクロプロパンカルボン酸（１Ｓ）－３－（２Ｚ）－（２－ブテニル）－２－メチル－４－オキソ－２－シクロペンテン－１－イルエステル＞、シネリンＩＩ＜（１Ｒ，３Ｒ）－３－［（１Ｅ）－３－メトキシ－２－メチル－３－オキソ－１－プロペニル］－２，２－ジメチルシクロプロパンカルボン酸（１Ｓ）－３－（２Ｚ）－（２－ブテニル）－２－メチル－４－オキソ－２－シクロペンテン－１－イルエステル＞、ジャスモリンＩ＜（１Ｒ，３Ｒ）－２，２－ジメチル－３－（２－メチル－１－プロペニル）シクロプロパンカルボン酸 （１Ｓ）－２－メチル－４－オキソ－３－（２Ｚ）－２－ペンテニル－２－シクロペンテン－１－イルエステル＞、ジャスモリンＩＩ＜（１Ｒ，３Ｒ）－３－［（１Ｅ）－３－メトキシ－２－メチル－３－オキソ－１－プロペニル］－２，２－ジメチルシクロプロパンカルボン酸 （１Ｓ）－２－メチル－４－オキソ－３－（２Ｚ）－２－ペンテニル－２－シクロペンテン－１－イルエステル＞、合成ピレスロイドとして、アレスリンＩ＜２，２－ジメチル－３－（２－メチル－１－プロペニル）シクロプロパンカルボン酸２－メチル－４－オキソ－３－（２－プロペニル）－２－シクロペンテン－１－イルエステル＞、アレスリンＩＩ＜３－（３－メトキシ－２－メチル－３－オキソ－１－プロペニル）－２，２－ジメチルシクロプロパンカルボン酸２－メチル－４－オキソ－３－（２－プロペニル）－２－シクロペンテン－１－イルエステル＞、フタルスリン（別名；Ｄ－テトラメトリン）＜（１，３－ジオキソ－４，５，６，７－テトラヒドロイソインドリン－２－イル）メチル＝２，２－ジメチル－３－（２－メチルプロパ－１－エン－１－イル）シクロプロパン－１－カルボキシラート＞、レスメトリン＜（５－ベンジル－３－フリル）メチル＝２，２－ジメチル－３－（２－メチルプロパ－１－エン－１－イル）シクロプロパンカルボキシラート＞、フェノトリン＜３－フェノキシベンジル＝２－ジメチル－３－（メチルプロペニル）シクロプロパンカルボキシラート＞、ペルメトリン＜３－フェノキシベンジル＝３－（２，２－ジクロロビニル）－２，２－ジメチルシクロプロパンカルボキシラート＞、シフェノトリン＜シアノ（３－フェノキシフェニル）メチル＝２，２－ジメチル－３－（２－メチルプロパ－１－エン－１－イル）シクロプロパンカルボキシラート＞、エトフェンプロックス＜４－（４－エトキシフェニル）－４－メチル－１－（３－フェノキシフェニル）－２－オキサペンタン＞、シフルトリン＜シアノ（４－フルオロ－３－フェノキシフェニル）メチル＝３－（２，２－ジクロロビニル）－２，２－ジメチルシクロプロパン－１－カルボキシラート＞、などが好ましい。そして、上記のうちペルメトリン、フェノトリン、アレスリン、フタルスリン、レストメトリンが、より好ましく、さらに、フェノトリン、アレスリンが最も好ましい。また、上記のピレスロイド系化合物は１種類のみ、又は２種類以上組み合わせて用いることができるが、２種類を組み合わせて用いることがより好ましい。 Insecticides or repellents include natural pyrethroids, which are active ingredients contained in insecticides, and synthetic pyrethroids, terpineol, eucalyptus oil, lemon oil, and citonella, which are derivatives of pyrethrin, and companions such as dogs, cats, rabbits, and hamsters. The insects such as fleas and ticks that parasitize mammals such as animals, cattle, pigs, chickens, and horses can be comatose or insecticidal. For example, as pyrethroid compounds, natural pyrethroids include pyrethrin I <(1R, 3R) -2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (1S) -2-methyl- 4-oxo-3- (2Z) -2,4-pentadienyl-2-cyclopenten-1-yl ester>, pyrethrin II <(1R, 3R) -3-[(1E) -3-methoxy-2-methyl- 3-oxo-1-propenyl] -2,2-dimethylcyclopropanecarboxylic acid (1S) -2-methyl-4-oxo-3- (2Z) -2,4-pentadienyl-2-cyclopenten-1-yl ester >, Cineline I <(1R, 3R) -2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (1S) -3- (2Z)-( -Butenyl) -2-methyl-4-oxo-2-cyclopenten-1-yl ester>, cineline II <(1R, 3R) -3-[(1E) -3-methoxy-2-methyl-3-oxo- 1-propenyl] -2,2-dimethylcyclopropanecarboxylic acid (1S) -3- (2Z)-(2-butenyl) -2-methyl-4-oxo-2-cyclopenten-1-yl ester>, jasmolin I <(1R, 3R) -2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (1S) -2-methyl-4-oxo-3- (2Z) -2-pentenyl- 2-cyclopenten-1-yl ester>, jasmolin II <(1R, 3R) -3-[(1E) -3-methoxy-2-methyl-3-oxo-1-propenyl] -2,2-dimethylcycl Ropropanecarboxylic acid (1S) -2-methyl-4-oxo-3- (2Z) -2-pentenyl-2-cyclopenten-1-yl ester>, as a synthetic pyrethroid, allethrin I <2,2-dimethyl-3 -(2-Methyl-1-propenyl) cyclopropanecarboxylic acid 2-methyl-4-oxo-3- (2-propenyl) -2-cyclopenten-1-yl ester>, Areslin II <3- (3-methoxy- 2-methyl-3-oxo-1-propenyl) -2,2-dimethylcyclopropanecarboxylic acid 2-methyl-4-oxo-3- (2-propenyl) -2-cyclopenten-1-yl ester>, phthalthrin ( Also known as D-tetramethrin) <(1,3-dioxo-4,5,6,7-tetrahydroisoindoline-2-yl) methyl = 2,2- Methyl-3- (2-methylprop-1-en-1-yl) cyclopropane-1-carboxylate>, resmethrin <(5-benzyl-3-furyl) methyl = 2,2-dimethyl-3- (2- Methylprop-1-en-1-yl) cyclopropanecarboxylate>, phenothrin <3-phenoxybenzyl = 2-dimethyl-3- (methylpropenyl) cyclopropanecarboxylate>, permethrin <3-phenoxybenzyl = 3- (2 , 2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate>, cyphenothrin <cyano (3-phenoxyphenyl) methyl = 2,2-dimethyl-3- (2-methylprop-1-en-1-yl ) Cyclopropanecarboxylate>, etofenprox <4- (4-ethoxypheny) ) -4-methyl-1- (3-phenoxyphenyl) -2-oxapentane>, cyfluthrin <cyano (4-fluoro-3-phenoxyphenyl) methyl = 3- (2,2-dichlorovinyl) -2, 2-dimethylcyclopropane-1-carboxylate> and the like are preferable. Of these, permethrin, phenothrin, allethrin, phthalthrin and restmethrin are more preferred, and phenothrin and allethrin are most preferred. Moreover, although said pyrethroid type compound can be used only in 1 type or in combination of 2 or more types, it is more preferable to use combining 2 types.
　昆虫成長阻害剤は、ノミやダニなどの害虫の卵、幼虫、又はサナギに付着するとそれらの成長を阻害する化合物で、その成長を阻害する機構については、脱皮をするための表皮に直接働きかけ新しい表皮を作成させない機構や、成長を促す化合物と拮抗することにより成長を抑制する機構など特に限定されない。例えば、昆虫成長阻害剤としては、ジフルベンズロン＜１－（４－クロロフェニル）－３－（２，６－ジフルオロベンゾイル）尿素＞、ピリプロキシフェン＜１－（４－フェノキシフェノキシ）－２－（２－ピリジルオキシ）プロパン＞、メトプレン＜（２Ｅ，４Ｅ）－１１－メトキシ－３，７，１１－トリメチルドデカ－２，４－ジエン酸イソプロピル＞、エトキサゾール＜２－（２，６－ジフルオロフェニル）－４－[４－（１，１－ジメチルエチル）－２－エトキシフェニル]－４，５－ジヒドロオキサゾール＞、ノバルロン＜（ＲＳ）－１－[３－クロロ－４－（１，１，２－トリフルオロ－２－トリフルオロメトキシエトキシ)フェニル]－３－(２，６－ジフルオロベンゾイル)ウレア＞、トリフロムロン＜１－（２－クロロベンゾイル）－３－（４－トリフルオロメトキシフェニル）尿素＞などが好ましい。そして、上記のうちジフルベンズロン、ピリプロキシフェン、メトプレンが、より好ましく、さらに、ピリプロキシフェンが最も好ましい。また、上記の昆虫成長阻害剤は１種類のみ、又は２種類以上組み合わせて用いることができる。 Insect growth inhibitors are compounds that inhibit the growth of fleas and ticks, such as fleas and ticks, when they adhere to eggs, larvae, or pupa. The mechanism of inhibiting the growth is directly applied to the epidermis for molting. There is no particular limitation such as a mechanism that does not create an epidermis or a mechanism that suppresses growth by antagonizing a compound that promotes growth. For example, insect growth inhibitors include diflubenzuron <1- (4-chlorophenyl) -3- (2,6-difluorobenzoyl) urea>, pyriproxyfen <1- (4-phenoxyphenoxy) -2- (2- Pyridyloxy) propane>, metoprene <(2E, 4E) -11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid isopropyl>, etoxazole <2- (2,6-difluorophenyl) -4 -[4- (1,1-dimethylethyl) -2-ethoxyphenyl] -4,5-dihydrooxazole>, Novallon <(RS) -1- [3-chloro-4- (1,1,2-tri Fluoro-2-trifluoromethoxyethoxy) phenyl] -3- (2,6-difluorobenzoyl) urea>, trifluorolone <1- (2-chlorobenzoyl) -3- (4-trifluoromethoxyphenyl) urea> and the like are preferable. Of these, diflubenzuron, pyriproxyfen and metoprene are more preferred, and pyriproxyfen is most preferred. In addition, the above insect growth inhibitors can be used alone or in combination of two or more.
　そして、本発明に係る動物向け外皮用製剤に、ペットの皮膚に付着したときにサラサラとした感触を付与するためポリエーテルシリコーンなど感触剤を添加することができ、また、抗真菌薬、抗菌薬、殺虫成分、忌避成分、昆虫成長阻害剤の酸化による劣化を防止するため、ビタミンＣ（アスコルビン酸）、ビタミンＥ（トコフェノール）、ＢＨＴ（ジブチルヒドロキシトルエン）、ＢＨＡ（ブチルヒドロキシアニソール）、ソルビン酸、ソルビン酸カリウム、亜硫酸ナトリウムなどの酸化防止剤を添加することができる。 In addition, to the animal skin preparation according to the present invention, a touching agent such as polyether silicone can be added to give a smooth feel when attached to the skin of a pet. Vitamin C (ascorbic acid), vitamin E (tocophenol), BHT (dibutylhydroxytoluene), BHA (butylhydroxyanisole), sorbic acid to prevent deterioration due to oxidation of insecticidal ingredients, repellent ingredients, insect growth inhibitors Antioxidants such as potassium sorbate and sodium sulfite can be added.
　さらに、爽快感を付与するためにｌ－メントールや本発明に係る動物向け外皮用製剤に香りを付けるために種々の香料を添加することができる。 Furthermore, various fragrances can be added to give fragrance to l-menthol and the animal skin preparation according to the present invention in order to give a refreshing feeling.
　そして、本発明に係る動物向け外皮用製剤を、ポアオン式の製剤として動物の体表面に塗布、そして拡散することができる。また、スプレー式の製剤として動物の体表面に塗布、そして拡散することができる。 Then, the animal skin preparation according to the present invention can be applied to the body surface of an animal and diffused as a pour-on preparation. It can also be applied to and spread on the surface of animals as a spray formulation.
　本発明の動物向け外皮用製剤における表面張力は、２５℃において、５０ｍＮ／ｍ以下であることが好ましく、１０～４６ｍＮ／ｍであることがさらに好ましく、１５～４１ｍＮ／ｍであることがもっとも好ましい。一般的に、表面張力は、板部材を液体表面に触れさせてその板部材を引き上げるときに働く力から算出するｗｉｌｈｅｌｍｙ法（プレート法）、鉛直方向に向けた細管の先端から押し出されてぶら下がった液滴の形状から算出する懸滴法（ペンダント・ドロップ法）、液体中に挿入したプローブ（細管）から気泡を連続的に発生させたときの最大圧力から算出する最大泡圧法など種々の方法によって測定される物性値であるが、本発明の動物向け外皮用製剤における表面張力は、ｗｉｌｈｅｌｍｙ法（プレート法）によって測定された値を基準に定められたものである。なお、本発明の動物向け外皮用製剤の接触角については、特に限定されるものではなく、当該製剤の表面張力と、動物の外皮の表面張力等から算出される。そして、当該製剤の表面張力が小さいとその接触角も小さくなり、動物の外皮に濡れ拡がり易いことを意味する。 The surface tension of the animal skin preparation of the present invention is preferably 50 mN / m or less at 25 ° C., more preferably 10 to 46 mN / m, and most preferably 15 to 41 mN / m. . In general, the surface tension is the Wilhelmy method (plate method), which is calculated from the force acting when the plate member is brought into contact with the liquid surface and pulls up the plate member. By various methods such as the hanging drop method (pendant drop method) that is calculated from the shape of the droplet, and the maximum bubble pressure method that is calculated from the maximum pressure when bubbles are continuously generated from a probe (capillary tube) inserted into the liquid. Although it is a physical property value to be measured, the surface tension in the animal skin preparation of the present invention is determined based on a value measured by the wihelmy method (plate method). The contact angle of the animal skin preparation of the present invention is not particularly limited, and is calculated from the surface tension of the preparation, the surface tension of the animal skin, and the like. And when the surface tension of the said formulation is small, the contact angle will also become small and it means that it will be easy to wet and spread to the outer skin of an animal.
　以下、本発明の実施例について具体的に説明する。なお、本発明は以下の実施例に限定されるものではない。 Hereinafter, examples of the present invention will be described in detail. In addition, this invention is not limited to a following example.
　＜実施例１＞
ナイスタチン０．２７ｇを２重量％水酸化ナトリウム水溶液１０ｇに、硫酸フラジオマイシン０．２５ｇとチオストレプトン０．２５ｇを精製水２０ｇに、トリアムシノロンアセトニド０．１ｇをエタノール１０ｇに、それぞれ別個に溶解し、その後それぞれの溶液をエチルジグリコール５６．１３ｇに混合、攪拌し、全量が１００ｇの動物向け外皮用製剤を得た。 <Example 1>
Dissolve 0.27 g of nystatin in 10 g of 2 wt% aqueous sodium hydroxide, 0.25 g of fradiomycin sulfate and 0.25 g of thiostrepton in 20 g of purified water, and 0.1 g of triamcinolone acetonide in 10 g of ethanol. Thereafter, each solution was mixed with 56.13 g of ethyl diglycol and stirred to obtain an animal skin preparation having a total amount of 100 g.
　＜実施例２＞
ナイスタチン０．２７ｇを２重量％水酸化ナトリウム水溶液１０ｇに、硫酸フラジオマイシン０．２５ｇとチオストレプトン０．２５ｇを精製水１０ｇに、トリアムシノロンアセトニド０．１ｇをエタノール２６ｇに、それぞれ別個に溶解し、その後それぞれの溶液をベンジルアルコール５３．１３ｇに混合、攪拌し、全量が１００ｇの動物向け外皮用製剤を得た。 <Example 2>
Dissolve 0.27 g of nystatin in 10 g of 2 wt% aqueous sodium hydroxide, 0.25 g of fradiomycin sulfate and 0.25 g of thiostrepton in 10 g of purified water, and 0.1 g of triamcinolone acetonide in 26 g of ethanol. Thereafter, each solution was mixed with 53.13 g of benzyl alcohol and stirred to obtain an animal skin preparation having a total amount of 100 g.
　＜実施例３＞
ナイスタチン０．２７ｇを２重量％水酸化ナトリウム水溶液１０ｇに、硫酸フラジオマイシン０．２５ｇとチオストレプトン０．２５ｇを精製水２０ｇに、トリアムシノロンアセトニド０．１ｇをエタノール２０ｇに、それぞれ別個に溶解し、その後それぞれの溶液をＮ－メチルピロリドン５９．１３ｇに混合、攪拌し、全量が１００ｇの動物向け外皮用製剤を得た。 <Example 3>
Dissolve 0.27 g of nystatin in 10 g of 2 wt% aqueous sodium hydroxide, 0.25 g of fradiomycin sulfate and 0.25 g of thiostrepton in 20 g of purified water, and 0.1 g of triamcinolone acetonide in 20 g of ethanol. Thereafter, each solution was mixed with 59.13 g of N-methylpyrrolidone and stirred to obtain an animal skin preparation having a total amount of 100 g.
　＜実施例４＞
フルコナゾール１．０ｇをエタノール１０ｇに溶解し、その後その溶液をエチルジクリコール８９ｇに混合、攪拌し、全量が１００ｇの動物向け外皮用製剤を得た。 <Example 4>
Fluconazole (1.0 g) was dissolved in ethanol (10 g), and then the solution was mixed with ethyl diglycol (89 g) and stirred to obtain an animal skin preparation with a total amount of 100 g.
　＜実施例５＞
塩酸テルビナフィン１．０ｇをエタノール１０ｇに溶解し、その後その溶液をブチルジクリコール８９ｇに混合、攪拌し、全量が１００ｇの動物向け外皮用製剤を得た。 <Example 5>
1.0 g of terbinafine hydrochloride was dissolved in 10 g of ethanol, and then the solution was mixed with 89 g of butyl diglycol and stirred to obtain an animal skin preparation having a total amount of 100 g.
　＜実施例６＞
ミコナゾール硝酸塩２．０ｇをプロピレングリコール２０ｇに溶解し、その後その溶液をエチルジクリコール７８ｇに混合、攪拌し、全量が１００ｇの動物向け外皮用製剤を得た。 <Example 6>
Miconazole nitrate (2.0 g) was dissolved in propylene glycol (20 g), and then the solution was mixed with ethyl diglycol (78 g) and stirred to obtain an animal skin preparation having a total amount of 100 g.
　＜実施例７＞
塩酸テルビナフィン１．０ｇをｐＨ３のクエン酸－リン酸緩衝液１０ｇに溶解し、その後その溶液をエチルジクリコール８９ｇに混合、攪拌し、全量が１００ｇの動物向け外皮用製剤を得た。 <Example 7>
1.0 g of terbinafine hydrochloride was dissolved in 10 g of a citrate-phosphate buffer solution having a pH of 3, and then the solution was mixed with 89 g of ethyl diglycol and stirred to obtain an animal skin preparation having a total amount of 100 g.
　＜比較例１＞
塩酸テルビナフィン１．０ｇをｐＨ３のクエン酸－リン酸緩衝液９９ｇに溶解し、全量が１００ｇの動物向け外皮用製剤を得た。 <Comparative Example 1>
1.0 g of terbinafine hydrochloride was dissolved in 99 g of a citrate-phosphate buffer solution having a pH of 3 to obtain an animal skin preparation having a total amount of 100 g.
　これらの実施例１～７、比較例１の組成を表１にまとめて示す。 Table 1 summarizes the compositions of Examples 1 to 7 and Comparative Example 1.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　各種組成物の拡散性について、以下の方法で確認した。すなわち、マウスの外皮に各種組成物を３０μＬ滴下したとき、所定時間経過後にその広がりの程度を計測した。滴下した地点から２ｃｍ以上広がったものを良好として「○」と、２ｃｍ未満しか広がらなかったものを不良として「×」と評価した。拡散性の良い組成物は、少量で広い面積に塗り広げることができるため、効率良く動物の外皮に塗布することができる。 The diffusibility of various compositions was confirmed by the following method. That is, when 30 μL of various compositions were dropped on the mouse skin, the extent of the spread was measured after a predetermined time. Those that spread 2 cm or more from the dropping point were evaluated as “good”, and those that spread less than 2 cm were evaluated as “bad” as poor. Since a composition having good diffusibility can be spread over a wide area with a small amount, it can be efficiently applied to the outer skin of animals.
　各種組成物の効果について、以下の方法で確認した。すなわち、菌液に各種組成物を滴下し、菌の繁殖が見られなかったものを良好として「○」と、菌が繁殖したものを不良として「×」と評価した。具体的には、まず、酵母であるカンジダ（Candida albicans ATCC10231）を白金耳で採取し、滅菌生理食塩液に浮遊させ、約１０８個／ｍＬの生菌を含む浮遊液を調整し、菌液とする。そして、各種組成物１０ｇを滅菌済みポリプロピレンチューブに分注し、これに菌液５０μＬを加え、さらに均一に混合されるように、ポリソルベート８０を１０％の割合で添加した滅菌生理食塩液５０μＬを加え、均一に分散させる。これらの試験検体を遮光下で２０～２５℃に保存する。そして、２８日後に被検組成物から１ｇを採取して、ろ過および滅菌処理をしたミリスチン酸イソプロピルに溶解し、１０倍に希釈する。そして、ポリソルベート８０を０．０５％の割合で添加した滅菌生理食塩液を用いて、さらに１０倍に希釈する。そして、生菌数を、寒天平板法により、２枚の平板を用いて測定した。 About the effect of various compositions, it confirmed with the following method. That is, various compositions were dropped into the bacterial solution, and those with no bacterial propagation were evaluated as “good”, and those with bacterial propagation were evaluated as “bad”. Specifically, first, Candida albicans ATCC10231 yeast is collected with a platinum loop, suspended in a sterilized physiological saline solution, and a suspension containing about 10 8 cells / mL viable bacteria is prepared. And 10 g of various compositions are dispensed into a sterilized polypropylene tube, 50 μL of bacterial solution is added thereto, and 50 μL of sterilized physiological saline with polysorbate 80 added at a ratio of 10% is added so as to be mixed evenly. , Uniformly disperse. These test specimens are stored at 20-25 ° C. in the dark. After 28 days, 1 g is collected from the test composition, dissolved in isopropyl myristate that has been filtered and sterilized, and diluted 10-fold. And it dilutes further 10 times using the sterilized physiological saline solution which added the polysorbate 80 in the ratio of 0.05%. Then, the viable cell count was measured using two flat plates by the agar plate method.
　各種組成物の表面張力について、以下の方法で確認した。すなわち、ｗｉｌｈｅｌｍｙ法による表面張力測定装置（協和界面科学社製、ＣＢＶＰ－３）にて、プレートとして白金を用いて、２５℃の下で、各種組成物にプレートが接触した直後の表面張力を読み取った。 The surface tension of various compositions was confirmed by the following method. That is, using a surface tension measuring device (CBVP-3, manufactured by Kyowa Interface Science Co., Ltd.) based on the Wilhelmy method, the surface tension immediately after the plate was brought into contact with various compositions at 25 ° C. was read. It was.
　これらの拡散性、効果、表面張力についての結果を表２に示す。 Table 2 shows the results of these diffusivities, effects, and surface tension.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　表２に示すように、実施例１～７では、表面張力が５０ｍＮ／ｍ以下と小さく、拡散性に優れ、菌に対する効果が高かった。しかし、比較例１では、菌に対する効果は高かったが表面張力が５０ｍＮ／ｍよりも大きく、拡散性に乏しかった。 As shown in Table 2, in Examples 1 to 7, the surface tension was as small as 50 mN / m or less, excellent in diffusibility, and highly effective against bacteria. However, in Comparative Example 1, although the effect on bacteria was high, the surface tension was larger than 50 mN / m, and the diffusibility was poor.

Claims (5)

  1. 抗真菌薬および抗菌薬の少なくとも１種と、
    極性を有する有機溶媒と、を含有し、液状であることを特徴とする動物向け外皮用製剤。     At least one of an antifungal agent and an antibacterial agent;
    An animal skin preparation comprising a polar organic solvent and liquid.
  2. ２５℃における表面張力が、５０ｍＮ／ｍ以下であることを特徴とする請求１に記載の動物向け外皮用製剤。 The animal skin preparation according to claim 1, wherein the surface tension at 25 ° C is 50 mN / m or less.
  3. 前記抗真菌薬および前記抗菌薬のうち少なくとも１種を、０．２～５０重量％含有することを特徴とする請求項１又は請求項２に記載の動物向け外皮用製剤。 The animal skin preparation according to claim 1 or 2, comprising 0.2 to 50% by weight of at least one of the antifungal agent and the antibacterial agent.
  4. 前記抗真菌薬が、ポリエン系、トリアゾール系、イミダゾール系、アリルアミン系から選択される１種又は２種以上であり、前記抗菌薬が、ペニシリン系、アミノグリコシド系、チオストレプトン系、グルコン酸塩系、ニューキノロン系、ステロイド系から選択される１種又は２種以上であることを特徴とする請求項１又は請求項２に記載の動物向け外皮用製剤。 The antifungal agent is one or more selected from polyene, triazole, imidazole, and allylamine, and the antibacterial agent is penicillin, aminoglycoside, thiostrepton, gluconate The animal skin preparation according to claim 1 or 2, wherein the preparation is one or more selected from quinolone, steroidal and steroidal.
  5. 前記極性を有する有機溶媒が、グリコール系化合物、ベンジルアルコール、Ｎ－メチルピロリドンから選択される１種又は２種以上であることを特徴とする請求項１又は請求項２に記載の動物向け外皮用製剤。 The animal skin according to claim 1 or 2, wherein the organic solvent having polarity is one or more selected from glycol compounds, benzyl alcohol, and N-methylpyrrolidone. Formulation.
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JP5551818B1 (en) * 2013-09-12 2014-07-16 持田製薬株式会社 Method for producing miconazole nitrate-containing solution formulation

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Publication number Priority date Publication date Assignee Title
JPH10109928A (en) * 1996-10-04 1998-04-28 Toko Yakuhin Kogyo Kk Aural cream preparation for animal
JP2011500790A (en) * 2007-10-25 2011-01-06 イーコラブ インコーポレイティド Use of metal astringents for the treatment and prevention of hair warts

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10109928A (en) * 1996-10-04 1998-04-28 Toko Yakuhin Kogyo Kk Aural cream preparation for animal
JP2011500790A (en) * 2007-10-25 2011-01-06 イーコラブ インコーポレイティド Use of metal astringents for the treatment and prevention of hair warts

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5551818B1 (en) * 2013-09-12 2014-07-16 持田製薬株式会社 Method for producing miconazole nitrate-containing solution formulation
JP2015054845A (en) * 2013-09-12 2015-03-23 持田製薬株式会社 Miconazole nitrate-containing solution formulation production method

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