WO2012147584A1 - Lotion en suspension contenant un agent antifongique de type imidazole - Google Patents

Lotion en suspension contenant un agent antifongique de type imidazole Download PDF

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Publication number
WO2012147584A1
WO2012147584A1 PCT/JP2012/060465 JP2012060465W WO2012147584A1 WO 2012147584 A1 WO2012147584 A1 WO 2012147584A1 JP 2012060465 W JP2012060465 W JP 2012060465W WO 2012147584 A1 WO2012147584 A1 WO 2012147584A1
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WO
WIPO (PCT)
Prior art keywords
lotion
butylene glycol
preparation
weight
imidazole
Prior art date
Application number
PCT/JP2012/060465
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English (en)
Japanese (ja)
Inventor
勇樹 芦塚
伊原　幹人
Original Assignee
マルホ株式会社
日本農薬株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by マルホ株式会社, 日本農薬株式会社 filed Critical マルホ株式会社
Priority to JP2013512294A priority Critical patent/JP5941909B2/ja
Publication of WO2012147584A1 publication Critical patent/WO2012147584A1/fr

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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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • 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
    • A61P17/08—Antiseborrheics
    • 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 relates to a lotion containing an imidazole antifungal agent. More specifically, the present invention relates to a drug-dispersed suspension lotion suitable for treating seborrheic dermatitis of the hair head.
  • Seborrheic dermatitis is dermatitis accompanied by light yellow greasy scales generated in seborrheic sites such as the head, face, and chest, and in the rubbing part. It is common in infants and adults, but is transient in infants, but is a chronic, recurrent disease in adults. Seborrheic dermatitis in adults is thought to have many etiologies such as abnormal metabolism of vitamin B group, abnormal sebum secretion, stress, etc. Recently, the involvement of Malassezia, a type of fungus, has been shown Various reports have been made on the usefulness of seborrheic dermatitis treatment with imidazole antifungal agents.
  • a surfactant is essential.
  • a preparation containing an oily component has a poor refreshing feeling, and a preparation containing a lower monohydric alcohol or a surfactant has a problem of irritation at a site where the preparation is applied.
  • the preparation containing an oil component since a solvent odor is generated, there is a problem that the odor adheres to the hair when used on the hair head.
  • Patent Document 1 and Patent Document 2 disclose a lotion agent containing ketoconazole, which is an imidazole antifungal agent
  • Patent Document 3 discloses a lotion agent containing luliconazole or ranoconazole.
  • the lotion of Patent Document 1 is an emulsion lotion obtained by emulsifying a base composed of an oily component and an aqueous component with a surfactant, and as described in the claims, An emulsifier (surfactant) is included as an essential component. Therefore, there is a problem that the irritation is strong and a problem that the refreshing feeling is inferior.
  • the lotion agent disclosed in Patent Document 2 (Claim 5, Example 6) is a solution obtained by completely dissolving ketoconazole, which is hardly soluble in water, using an organic solvent (propylene carbonate or ethanol). Is a lotion obtained by diluting with water (ie, a solution lotion).
  • propylene carbonate is irritating to the eyes and respiratory organs, and lower monohydric alcohols such as ethanol are highly volatile, and there is a concern that the effects on the skin due to addition to external preparations are a concern. is there. There is also a problem that an ethanol odor is generated.
  • the lotion disclosed in Patent Document 3 is an emulsion lotion containing an oily base and an emulsifier as described in Claim 5, as with the lotion of Patent Document 1, irritation and use There is concern about feeling.
  • JP 2003-113083 A Japanese Patent No. 3007146 WO2009 / 028495
  • the present inventors do not include a lower monohydric alcohol such as ethanol, a surfactant and an oily base for a preparation containing an imidazole antifungal agent, improve the feeling of use such as stickiness, and An attempt was made to produce a solution lotion with reduced irritation.
  • a lower monohydric alcohol such as ethanol
  • a surfactant and an oily base for a preparation containing an imidazole antifungal agent
  • the method of manufacturing could not overcome the problem of dissolving imidazole antifungals in an aqueous solvent that does not contain lower monohydric alcohol.
  • a preparation having a refreshing feeling of use, excellent skin permeability, and uniform content over time is obtained. The present invention was completed successfully.
  • the present invention is a lotion containing an imidazole antifungal agent, 90% particle diameter (D 90 ) of the imidazole antifungal is 30 ⁇ m or less, A suspension lotion containing 1,3-butylene glycol and water, No surfactant and lower monohydric alcohol, It is characterized by.
  • the lotion is a liquid preparation, it is easy to apply to the head of hair, and since it does not contain a surfactant and a lower monohydric alcohol, it is less irritating to the skin.
  • it is a suspension lotion and does not contain an oil component (oil base), so it has a refreshing feeling.
  • fine particles with 90% particle size (D 90 ) of 30 ⁇ m or less as imidazole antifungal drugs (main drug) it is possible to prevent unevenness of the main drug content in the drug product due to sedimentation and Content uniformity can be ensured.
  • main drug fine particles with 90% particle size of 30 ⁇ m or less as imidazole antifungal drugs (main drug)
  • main drug imidazole antifungal drugs
  • the skin permeability can be promoted, so that excellent medicinal effects can be exhibited.
  • the aqueous solvent which does not contain an oil-based component and a lower monohydric alcohol is used, there is almost no solvent odor.
  • the preparation of the present invention is a lotion, it is easy to apply to the head of the hair.
  • it does not contain lower monohydric alcohols, surfactants and oily ingredients, so it has low irritation, has a refreshing feeling and is almost odorless. .
  • it is excellent in skin permeability and content uniformity of the active ingredient.
  • FIG. 1 is a graph showing the results of an in vitro human skin permeability test on the lotions of the present invention and comparative examples.
  • the lotion of the present invention is classified as a suspension lotion. That is, lotions include emulsion lotions, solution lotions, and suspension lotions. Emulsion lotions are composed of an oily component and an aqueous component, and these are emulsified with a surfactant. Let me.
  • the solution lotion and the suspension lotion are common in that the base is a lotion composed of an aqueous component and may or may not contain a surfactant.
  • the active ingredient exists in a dissolved form, and in a suspension lotion, the active ingredient does not dissolve but exists in a dispersed form.
  • the suspending lotion of the present invention is characterized by not containing a surfactant (emulsifier) or a lower monohydric alcohol (monohydric alcohol having 1 to 3 carbon atoms such as ethanol or isopropanol).
  • the active ingredient of the lotion of the present invention is an imidazole antifungal agent.
  • imidazole antifungal agents include lanconazole, luliconazole, itraconazole, ketoconazole, fluconazole, econazole and the like. Ranoconazole or luliconazole is particularly preferred.
  • the content in the lotion is preferably about 0.1 to 3% by weight, more preferably 0.5 to 3% by weight, and particularly preferably 0.5 to 2% by weight.
  • the imidazole antifungal drug needs to have a 90% particle size (D 90 ) of 30 ⁇ m or less.
  • the 90% particle diameter (D 90 ) means a 90% cumulative particle diameter from the fine particle side measured by a laser diffraction scattering method. That is, in the particle size distribution measured by the laser diffraction scattering method, 90% by volume of the particles may be distributed in a particle size range of 30 ⁇ m or less (about 0.1 ⁇ m to 30 ⁇ m).
  • a more preferable imidazole antifungal agent is a fine powder having a D 90 of 20 ⁇ m or less, and particularly preferably a fine powder having a D 90 of 15 ⁇ m or less.
  • the base (solvent) of the lotion of the present invention consists of only an aqueous component and necessarily contains water and 1,3-butylene glycol. Furthermore, it may contain glycerin and may contain other aqueous components (aqueous base). As described above, the lotion of the present invention does not contain oil components (hydrocarbons, fatty acid esters, waxes, triglycerides, higher fatty acids, higher alcohols, etc.).
  • the lotion preferably contains 1 to 50% by weight of 1,3-butylene glycol, more preferably 2 to 20% by weight. If the concentration of 1,3-butylene glycol is less than 1% by weight, it is difficult to obtain the desired skin permeability promoting effect, and if it is more than 50% by weight, it causes problems such as stickiness and irritation to the skin. Is likely to occur.
  • a more preferred concentration of 1,3-butylene glycol is 5 to 15% by weight.
  • water is preferably contained in an amount of 40 to 98% by weight, more preferably 50 to 95% by weight, and even more preferably 75 to 94% by weight. Further, when glycerin is added, the amount is preferably 15% by weight or less. If used in an amount exceeding 15% by weight, the skin permeability of the imidazole antifungal agent may be lowered.
  • the lotion of the present invention contains water and 1,3-butylene glycol in total 90% by weight (more preferably 95% by weight) or more, or water, 1,3-butylene glycol and glycerin in total 90% by weight. % (More preferably 95% by weight) or more is preferable.
  • the solvent consists of water and 1,3-butylene glycol only, or water, 1,3-butylene glycol and glycerin. By constituting the solvent only from these components, an excellent lotion agent having almost no irritation and odor can be obtained.
  • the lotion of the present invention preferably has a viscosity of 1000 to 3000 mPa ⁇ s. If the viscosity is less than 500 mPa ⁇ s, the fluidity is high and it tends to sag when applied to the head, and if the viscosity is 3500 mPa ⁇ s or more, the fluidity is low and it is close to a gel, so it tends to adhere to the hair. The feeling of use also gets worse. By setting the viscosity within the range of 1000 to 3000 mPa ⁇ s, it is possible to prevent the formulation from flowing down when used on the head, and to obtain a formulation free from unpleasant feeling of use such as stickiness.
  • a preferred viscosity range is 1500 to 2500 mPa ⁇ s, and a more preferred viscosity range is 1500 to 2200 mPa ⁇ s.
  • the viscosity means a viscosity when measured with a B-type viscometer (B8H, rotor) at a measurement temperature of 25 ° C. and a rotation speed of 50 rpm for 10 seconds.
  • the lotion of the present invention preferably contains a thickener in order to obtain the above viscosity.
  • Particularly preferred thickeners include carboxyvinyl polymer and xanthan gum.
  • the amount of the thickener in the lotion may be an amount that can achieve the viscosity.
  • carboxyvinyl polymer when carboxyvinyl polymer is used as a thickener, 0.1 to 1.0% by weight (more preferably 0.2 to 0.5% by weight) is appropriate.
  • suitable carboxyvinyl polymers include polymers containing 56 to 68% carboxyl groups, more preferably 58 to 63% (wt% of carboxyl groups in the carboxyvinyl polymer). Such carboxyvinyl polymers are commercially available.
  • a viscosity stabilizer may be added. For example, sodium edetate hydrate can be used in an amount of about 0.02 to 0.1% by weight.
  • the lotion preferably has a pH in the range of 4-7. If the pH is 9.0 or more, the main drug will be easily decomposed. In order to ensure hypoallergenicity, stability of the active ingredient and physical properties, a pH in the above range is preferred. In addition, when using a carboxy vinyl polymer as a thickener, it is preferable that pH is 5.0 or more. By setting it to 5.0 or more, the carboxyvinyl polymer can be sufficiently thickened. Suitable pH adjusters include diisopropanolamine, L-arginine, potassium hydroxide, sodium hydroxide. A particularly preferred pH adjusting agent is diisopropanolamine which is easy to adjust pH. The amount of the pH regulator in the lotion may be an amount that can achieve the pH. For example, in the case of diisopropanolamine, about 0.1 to 1.5% by weight is appropriate.
  • the lotion preferably contains a preservative (preservative).
  • preservatives include methyl paraoxybenzoate, ethyl paraoxybenzoate, phenoxyethanol, benzalkonium chloride, salicylic acid, chlorocresol and the like. Particularly preferred preservatives are methyl paraoxybenzoate or ethyl paraoxybenzoate.
  • the amount of the preservative in the lotion may be the amount generally used in skin lotions. For example, in the case of parabens (methyl paraoxybenzoate, ethyl paraoxybenzoate), about 0.05 to 0.25% by weight is appropriate.
  • the lotion of the present invention may contain components blended in a normal skin lotion, such as a dye, a fragrance, a pigment, an antioxidant, and an ultraviolet absorber, if necessary.
  • An example of a method for producing the lotion of the present invention (containing the above-mentioned preservative, thickener, pH adjuster and viscosity stabilizer) is shown below.
  • a preservative solution and 1,3-butylene glycol (1,3-butylene glycol and glycerin when glycerin is used) are stirred and dissolved to prepare a preservative solution.
  • (2) Stir and dissolve purified water and thickener to prepare a thickener aqueous solution.
  • (3) Stir and dissolve purified water and a pH regulator to prepare an aqueous pH regulator solution.
  • Add an imidazole antifungal agent to the solution of (4) and disperse with stirring.
  • (6) Add an aqueous pH adjuster solution to (5), mix with stirring, and add an appropriate amount of purified water.
  • Comparative Example 1 Comparison in the same manner as in Example except that 1,3-butylene glycol was not used and only glycerin was used in (1) of the above production method, and no 1,3-butylene glycol was contained.
  • the suspension lotion of Example 1 was produced.
  • Comparative Example 2 (1) of the above production method was not carried out, but in (4), except for the paraben solution, the mixture was stirred and mixed, and dissolved in the same manner as in Examples, except that 1,3-butylene glycol, glycerin, A suspension lotion of Comparative Example 2 containing no paraben was produced.
  • Test Example 1 In vitro human skin permeability test The lotion preparations of Examples 1 to 7 and Comparative Examples 1 and 2 were subjected to an in vitro human skin permeability test by the following method. As a control, a commercially available ranoconazole preparation, ASTAT (registered trademark) cream 1% (ASTAT cream: cream containing 10 mg of ranoconazole in 1 g) was used.
  • ASTAT registered trademark
  • An in vitro permeability test was performed using an automatic transdermal absorption test system (MicroEtte Plus) equipped with a Franz vertical diffusion cell. Using human skin adjusted to a thickness of 0.5 mm as the permeable membrane, apply 10 mg of the test substance on the permeable membrane, and stir with a stir bar while maintaining the receptor solution (phosphate buffered saline solution containing 15% ethanol) at 32 ° C. The amount of permeation through the skin 4, 8, 12, 16 hours after application of the test substance was quantified by LC / MS / MS (liquid chromatograph-tandem mass spectrometer).
  • FIG. 1 shows the cumulative permeation amount of Ranoconazole. This test was conducted using human skin tissue. Since there are individual differences in the permeability of the formulation to the skin, even in in vitro tests, the cumulative amount of permeation often varies with different skin tissue donors. Therefore, in the test using skin tissue, it is necessary to compare the permeation amount of the control and the test preparation and judge the superiority or inferiority of the permeability. It shows permeability.
  • the lotion of the present invention showed a skin permeability superior to that of ASTAT cream.
  • the lotion preparation of Comparative Example 1 containing no glycerin but not 1,3-butylene glycol resulted in inferior skin permeability as compared to ASTAT cream.
  • the lotion preparation of Comparative Example 2 that does not contain 1,3-butylene glycol and glycerin showed skin permeability almost equivalent to that of ASTAT cream. Note that the lotion preparation of Comparative Example 2 does not contain 1,3-butylene glycol or glycerin, so the preservative (paraben) cannot be dissolved, and the preservative is more storable than the lotion preparation or aster cream of the example. The preparation was inferior.
  • 1,3-butylene glycol has an effect of promoting the skin permeability of lanoconazole. Therefore, when a large amount (45% by weight) of 1,3-butylene glycol is used as in Example 3, the skin permeability of the imidazole antifungal agent is very good. In view of formulation characteristics other than skin permeability, the amount of 1,3-butylene glycol is 50% by weight or less (preferably 20% by weight or less, more preferably 15% by weight or less) is appropriate. On the other hand, in the preparation to which glycerin was added, there was a tendency that the skin permeability of ranoconazole was suppressed as compared with the preparation not to be added.
  • the combined use of 1,3-butylene glycol and glycerin can regulate the skin permeability of ranoconazole.
  • the amount of glycerin is preferably added in an amount that does not interfere with the skin permeability promoting effect of 1,3-butylene glycol, and is preferably used at a concentration of 15% by weight or less.
  • Example 2 Evaluation of content uniformity (uniformity at -5 ° C, storage for 13 weeks) Each formulation of Example 2 and Comparative Example 3 is dispensed into containers and stored at -5 ° C for 13 weeks. Thereafter, the ranconazole concentration of the preparation sampled from the upper, middle and lower portions of the container was measured by HPLC, and the ratio to the starting concentration (10 mg / L) was compared. The results are shown in Table 3.
  • Test Example 3 Evaluation of skin irritation Damaged skin is provided on the back skin of rabbits, and 0.05 g of the test substance (lotions or aster creams of Examples 2 and 8) per day is administered openly for 23 hours, continuously for 7 days. Administered. The number of animals was 3 for each. The skin reaction was determined according to Draize criteria 1) . Table 4 shows the criteria for Draize.
  • Example 2 and Example 8 do not cause any erythema or edema on the skin even when applied to the skin, are less irritating than existing aster cream, It was also found that there was no irritation at all.
  • Viscosity stability test The lotion preparation of Example 2 was subjected to a viscosity stability test. The test method is shown below. (1) Store the test preparation (the lotion preparation of Example 2) at 40 ° C / 75% RH or 60 ° C for 13 weeks. (2) Viscosity of the preparation before and after storage (after 13 weeks) using a B-type viscometer (B8H, rotor: HH-12, measurement temperature 25 ° C., rotation speed 50 rpm, 10 seconds) was measured. The results are shown in Table 7.
  • the lotion of Example 2 maintains a viscosity of 1500 mPa ⁇ s or more even when stored under accelerated conditions of 40 ° C and 75% RH or severe conditions of 60 ° C for 13 weeks. When applied to the hair head, it was difficult to sag and could prevent the eyes and ears from falling off.
  • the lotion preparation of the present invention is a cellulose-based thickener (hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, ethylcellulose, etc.) often used in external preparations for skin. It has been found that it is preferable to use a carboxyvinyl polymer rather than to use). When a cellulosic thickener was used, it was confirmed that the viscosity decreased with time and that ranoconazole was precipitated.
  • a cellulose-based thickener hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, ethylcellulose, etc.
  • carboxyvinyl polymer thickener
  • sodium edetate hydrate viscosity stabilizer
  • Test formulation A. Commercial O / W emulsion lotion containing ketoconazole: (ketoconazole [active ingredient], oily base [squalane], surfactant [glyceryl monostearate, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene cetyl] Ether]) B. Lotion of Example 2
  • Table 8 shows the evaluation criteria and results.
  • Example 2 As can be seen from Table 8, the lotion preparation of Example 2 was very well evaluated for sagging and stickiness, and was found to be superior to the commercially available preparation (Test preparation A). Further, the lotion preparation of Example 2 was an almost odorless lotion, and when applied to the hair, no odor adhered to the hair.
  • the lotion of the present invention does not contain a lower monohydric alcohol, a surfactant, and an oil component (oil base), so it is very low in irritation and refreshed. It has a good feeling of use. Moreover, since the main ingredient has excellent skin permeability, excellent medicinal effects can be obtained.
  • the lotion of the present invention is very suitable for use in seborrheic dermatitis of the hair head.

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  • Health & Medical Sciences (AREA)
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Abstract

La présente invention a pour objet une lotion contenant un agent antifongique de type imidazole, qui présente une excellente aptitude à l'absorption de l'ingrédient principal par voie transdermique et qui présente un caractère hypoallergénique et une sensation fraîche lors de l'application. La lotion selon l'invention contient un agent antifongique de type imidazole et elle est caractérisée en ce que l'agent antifongique de type imidazole a un diamètre des particules à 90 % (D90) inférieur ou égal à 30 µm et la lotion est une lotion en suspension contenant du 1,3-butylèneglycol et de l'eau et ne contient aucun tensioactif ou aucun monoalcool inférieur.
PCT/JP2012/060465 2011-04-27 2012-04-18 Lotion en suspension contenant un agent antifongique de type imidazole WO2012147584A1 (fr)

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JP2013512294A JP5941909B2 (ja) 2011-04-27 2012-04-18 イミダゾール系抗真菌薬を含有する懸濁性ローション剤

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JP2011-099115 2011-04-27
JP2011099115 2011-04-27

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5951864B1 (ja) * 2015-06-05 2016-07-13 株式会社ポーラファルマ 抗ジアルジア剤
JP2017002033A (ja) * 2015-06-04 2017-01-05 大正製薬株式会社 外用組成物
JP6085706B1 (ja) * 2016-03-31 2017-02-22 株式会社ポーラファルマ 抗トリトリコモナス剤
WO2019070221A1 (fr) * 2017-10-03 2019-04-11 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Compositions pharmaceutiques topiques de luliconazole

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61151117A (ja) * 1984-12-25 1986-07-09 Bayer Yakuhin Kk 抗真菌ゲル製剤
JPH1121229A (ja) * 1997-06-30 1999-01-26 Kyoto Yakuhin Kogyo Kk 抗真菌性外用製剤およびその製造方法
WO2007102243A1 (fr) * 2006-03-08 2007-09-13 Nihon Nohyaku Co., Ltd. Composition pharmaceutique externe

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61151117A (ja) * 1984-12-25 1986-07-09 Bayer Yakuhin Kk 抗真菌ゲル製剤
JPH1121229A (ja) * 1997-06-30 1999-01-26 Kyoto Yakuhin Kogyo Kk 抗真菌性外用製剤およびその製造方法
WO2007102243A1 (fr) * 2006-03-08 2007-09-13 Nihon Nohyaku Co., Ltd. Composition pharmaceutique externe

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017002033A (ja) * 2015-06-04 2017-01-05 大正製薬株式会社 外用組成物
JP5951864B1 (ja) * 2015-06-05 2016-07-13 株式会社ポーラファルマ 抗ジアルジア剤
WO2016194024A1 (fr) * 2015-06-05 2016-12-08 Pola Pharma Inc. Agent anti-giardiase
JP6085706B1 (ja) * 2016-03-31 2017-02-22 株式会社ポーラファルマ 抗トリトリコモナス剤
WO2017168476A1 (fr) * 2016-03-31 2017-10-05 Pola Pharma Inc. Agent anti-tritrichomonas
WO2019070221A1 (fr) * 2017-10-03 2019-04-11 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Compositions pharmaceutiques topiques de luliconazole

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JPWO2012147584A1 (ja) 2014-07-28
TW201249476A (en) 2012-12-16

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