WO1994015591A1 - Composition de traitement de l'onychomycose - Google Patents

Composition de traitement de l'onychomycose Download PDF

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Publication number
WO1994015591A1
WO1994015591A1 PCT/JP1994/000028 JP9400028W WO9415591A1 WO 1994015591 A1 WO1994015591 A1 WO 1994015591A1 JP 9400028 W JP9400028 W JP 9400028W WO 9415591 A1 WO9415591 A1 WO 9415591A1
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WO
WIPO (PCT)
Prior art keywords
weight
composition
nail
drug
ethanol
Prior art date
Application number
PCT/JP1994/000028
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English (en)
Japanese (ja)
Inventor
Akira Nakagawa
Satoru Miyata
Kenzo Sakai
Original Assignee
Hisamitsu Seiyaku Kabushiki Kaisha
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.)
Filing date
Publication date
Application filed by Hisamitsu Seiyaku Kabushiki Kaisha filed Critical Hisamitsu Seiyaku Kabushiki Kaisha
Publication of WO1994015591A1 publication Critical patent/WO1994015591A1/fr

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/85Polyesters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37Esters of carboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/731Cellulose; Quaternized cellulose derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8129Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers or esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers, e.g. polyvinylmethylether
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015Drug-containing film-forming compositions, e.g. spray-on
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q3/00Manicure or pedicure preparations

Definitions

  • the present invention relates to a composition for treating tinea versicolor, which contains an antifungal agent as an active ingredient. More specifically, the present invention contains an antifungal agent as an active ingredient .. This is mixed with a drug having an effect of promoting absorption of the drug into the nails.
  • Nail leukoplakia is a nail disease caused by filamentous fungi and is a stubborn disease accompanied by opacity, thickening, destruction, and deformity of the nail plate.
  • an external preparation containing an antifungal agent or an oral preparation containing Griseofulvin has been known, but in the conventional external preparation, the nail preparation is Due to the hard keratin of the skin, the drug could not penetrate inside the nail, and the effect could hardly be achieved.
  • an oral administration agent containing griseofulvin was usually used. It is mainly used.
  • Japanese Patent Application Laid-Open No. 62-1552505 discloses a liquid medicine containing 1-hydroxy-2-pyridone.
  • Japanese Patent Application Laid-Open No. 2-267047 discloses an antifungal agent using a acrylate ester and a polymer / metacrylate ester as a film-forming agent.
  • Ringworms such as tinea pedis (athlete's foot) and tinea pedis that cannot be obtained as therapeutic agents are extremely irreversible diseases because they are hard to penetrate because they grow deep in the keratin.
  • tinea unguium It is difficult to treat even on the hands and feet, but especially in the case of tinea unguium; since the keratin of the nail is hard, the drug penetration is poor, and it is impossible to cure tinea unguium with topical agents until now It has been thought that the treatment of tinea unguium is such that it is important to allow the drug to penetrate into the stratum corneum and store it for a long period of time. For the purpose of treating nail leukoplakia, no preparation has been found that has excellent penetrability and retention in the horny layer of the nail and exerts its therapeutic effect satisfactorily.
  • An object of the present invention is to provide a pharmaceutical composition for treating tinea unguium, which is excellent in the adhesiveness, penetrability and retention of drug components to the corneum of the nail.
  • the present invention provides a composition for the treatment of Aspergillus niger, which comprises a base containing a fatty acid ester, an aqueous lacquer film-forming agent and a solvent, and an antifungal agent combined with the base below.
  • a composition for the treatment of Aspergillus niger which comprises a base containing a fatty acid ester, an aqueous lacquer film-forming agent and a solvent, and an antifungal agent combined with the base below.
  • Examples of the antifungal agent as the active ingredient of the present invention include terbinafine hydrochloride, neticoconazol hydrochloride / re, omoconazol nitrate, butenafine hydrochloride, isoconazole nitrate, miconazole nitrate, and Examples include econazole nitrate, sulconazole nitrate, oxiconazole nitric acid, thioconazole, tolucyclyl cosoconazole, miconazole nitrate, econazole nitrate, sulconazol nitrate / re, and oxyconazol nitrate / re.
  • omoconazol nitrate / resin and butenafine hydrochloride are particularly preferable because they have high permeability to the stratum corneum and excellent storability in the stratum corneum. is there .
  • the antifungal agent as an active ingredient is blended in an amount of 0.3 to 5% by weight, preferably 0 ⁇ 5 to 3% by weight. If the compounding amount is too small, the effect will not be sufficiently obtained, and if the compounding amount is too large, the drug will not dissolve in the solvent, and there is a formulation problem, which is not preferable.
  • the fatty acid ester as a component include Sebac
  • diisopropyle quinoate diisopropyle quinoate
  • benzyl ethenosuccinate diisopropylate adipate
  • jeti / lepi adipate diisopropyl sebacate b, which is effective as a solvent, has the most excellent effect of promoting absorption of the drug into the nail.
  • Hydrophobic film-forming agents include pyroxylline (nitrocellulose moistened with isopropanol or other suitable solvent), alkyd resin, acrylic acid.
  • pyroxylline nitrocellulose moistened with isopropanol or other suitable solvent
  • alkyd resin acrylic acid.
  • Styrene copolymer acrylic acid ⁇ Meta-acrylic acid amide copolymer, butyl acrylate ⁇ Meta-acrylic acid copolymer, acrylic acid hydroxide Cypropill-meta-acryl octyl acrylate Noetyl 'acrylate octyl amide copolymer, acryl amide ⁇ Polyvinyl alcohol copolymer, methacryl dimethyl acrylate Noethyl-methacrylic acid ester copolymer, acrylic acid-methacrylic acid methyl-methacrylic acid-methacrylic acid ammonium-methylammoniumethyl copolymer
  • the resin include ethylene resin, ethylene-vinyl a
  • Solvents include ethyl acetate, butyl acetate, acetone, methyl ethyl ketone, methyl isobutyl ketone, and adipic acid.
  • the amount of the film forming agent is 0.5 to 35% by weight, preferably 1 to 20% by weight, using the above substances alone or in combination. If it is 0.5% or less, the adhesiveness of the drug to the nail is poor, and if it is 35% by weight or more, the coating becomes thick and the usability is poor, and the absorbability of the drug to the nail is also reduced. Solvents may be used alone or in combination at 20 to 96% by weight, preferably 70 to 95% by weight. If it is less than 20% by weight, it will be difficult to dissolve the drug, and if it is more than 96% by weight, it will be difficult to mix other ingredients. Fatty acid esters are blended in a proportion of 0.2 to 20% by weight, preferably 1 to 10% by weight.
  • plasticizers for film-forming agents such as camphor, phthalic acid esters, quinic acid esters, castor oil, etc. can be blended as necessary.
  • Fatty acid esters were 17% by weight of diisopropyl sebacate and a hydrophobic film-forming agent. Then, 15% by weight of pyroxylline and 12% by weight of the alkyd resin were dissolved in a solvent consisting of 33% by weight of ethyl acetate, 10% by weight of ethanol and 7% by weight of toluene. 1% by weight of ocomonazole nitrate as an antifungal agent was stirred and uniformly dissolved in this solution to obtain a composition for treating tinea unguium containing an antifungal agent.
  • composition Ingredients wt% Omoconazole nitrate 1 Pyroxylline 5 Polyvinyl butyral 15 Disopropyl adipate 3 Ethanol 76
  • composition Ingredients% by weight omoconazole nitrate 1 Soluble nitrogen 20 Ethyl acetate 28 Ethanol 46 Ethyl enosuccinate 5
  • composition Ingredients wt% Omoconazole nitrate 3 Acrylic acid resin (Eudragit ⁇
  • composition Ingredients% by weight Omoconazole Nitrate 5 pi ⁇ -xylene 15 alk ,, / resin 12 camp
  • Composition Ingredients% by weight Butenafin hydrochloride 1 Pyroxylline 15 Aki, Zodo resin 12 Camphor 5 Disopropyl senohexanoate 17 Ethyl acetate; Re 33 Ethano -Nore 10
  • composition component wt% Composition component wt%
  • composition Ingredients% by weight Butenafine hydrochloride 3 pi ⁇ xylline 15 Polyvinylacetate Jetyl
  • Example 10 2573 ⁇ Composition Ingredients% by weight Butenafin Hydrochloride 3 Pycylline 15 Polyvinylacetate Jetyl
  • Composition Ingredients% by weight Omoconazole Nitrate 3 Pi ⁇ -xylline 15 cN—Kan'Far 2 Propylene Carbonate 4 Diisopate Sebac Pill 3 Ethyl Acetate 15 Ethanol 40 Petit Acetate / Le 18
  • composition Ingredients% by weight Omoconazole Nitrate 3 sigma Xylline 10 Acetone 20 d I—Kampha 2 Adipic Acid Disoup Pill
  • composition Ingredients% by weight
  • composition Ingredients% by weight
  • Composition Ingredients% by weight Econazole Nitrate 3 Pyroxylline 15 cM—Camper 2 Ace 20 20 Dizop sebacate pill 2 — Ethyl acetate 28 Ethanol 15 Butyl acetate 15
  • Composition Ingredients wt% Oxiconazole nitrate 3 Pyroxylline 15 d l — Camphor 2 Aceton 20 Disopropil senocinate 2 Ethyl acetate 23 Ethanol 15 Butyl acetate 20
  • composition Ingredients% by weight Sulconazole nitrate 3 pi ⁇ xylline 5 d I — Camphor 2 Propylene carbonate 4 Cenosuccinic acid disodium pill
  • composition Ingredients .M.A Nitrate nitrate
  • Composition Ingredients 3 ⁇ 4 i. Tioconazole 3 Pyroxylline 5 d I — Camphor 2 Propylene carbonate 4 Diisopropyl sebacate 3 Ethyl acetate 25 Ethanol 40 Butyl acetate 18
  • composition Ingredients% by weight Exalamide 3 Pyroxylline 5 d I—Campane 2 Propylene carbonate 4 Disodium cisenoate mouth
  • composition Ingredients% by weight Nitric acid "10 oz. 3 p ⁇ zizirine
  • composition Ingredients% by weight Omoconizo nitrate 3 p ⁇ xylline 10 d! 1 camp 2 ace 20
  • Pork claws were punched out using a 1 CI diameter skin punch.
  • the preparation of the present invention was applied thinly on the surface of the nail using a brush.
  • the applied nail is saline It was placed on gauze moistened with water and left at 25 C. Two hours after administration, the residual drug at the administration site was wiped off with gauze moistened with ethanol, and then the nail was punched out with a skin punch to a size of 4 mni to obtain a sample.
  • the nail was fixed on the cryostat stage with the coated surface facing the CMC, and a 5m-thick section was made using a cryostat (Leitz 1720 d ig i ta l Cryostat, Le i ca). did.
  • the 10 slices were collected and collected in a vial, and the radioactivity was measured with a liquid scintillation counter (PACKARD, TRI-CARB 1600TR).
  • the amount of absorbed omoconazole nitrate was calculated and converted to a concentration per unit volume, and AUC was also determined from that concentration.
  • the composition for the treatment of nail polish of the present invention which is shown in the above-mentioned example, is superior in drug absorption as compared with the preparation containing no fatty acid esters. Ruko was recognized.
  • composition for treating tinea cruris according to the present invention is as irritating as white petrolatum, with almost no irritation to skin thorns and ⁇ .
  • composition for the treatment of nail whitening according to the present invention has a high permeability and retention of the drug to the horny layer of the nail, and the drug penetrates into the nail and is retained for a long time in the nail, which is excellent. Antifungal The effect is obtained. In addition, it is also highly safe with almost no irritation in Hibaru.
  • the composition for treating tinea unguium according to the present invention is extremely excellent as a therapeutic agent for tinea unguium, which has not been able to obtain a therapeutic effect when applied externally.
  • Figure 1 shows the results of the pig nail absorption test of Test Example 1.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Birds (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Composition de traitement de l'onychomycose comprenant un fongicide et une base constituée d'un agent formant un film hydrophobe, d'un ester d'acide gras et d'un solvant. Cette composition est liquide et se caractérise par d'excellentes propriétés d'adhérence et de pénétration dans le cuticule de l'ongle, et une forte tenue.
PCT/JP1994/000028 1993-01-12 1994-01-12 Composition de traitement de l'onychomycose WO1994015591A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP5/20692 1993-01-12
JP5020692A JPH06211651A (ja) 1993-01-12 1993-01-12 爪白癬治療用組成物

Publications (1)

Publication Number Publication Date
WO1994015591A1 true WO1994015591A1 (fr) 1994-07-21

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ID=12034214

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1994/000028 WO1994015591A1 (fr) 1993-01-12 1994-01-12 Composition de traitement de l'onychomycose

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JP (1) JPH06211651A (fr)
WO (1) WO1994015591A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1374905A1 (fr) * 2002-06-25 2004-01-02 Ethicon, Inc. Compositions injectables pour applications médicales
US6872799B2 (en) 2002-12-18 2005-03-29 Ethicon, Inc. Functionalized polymers for medical applications
US6967234B2 (en) 2002-12-18 2005-11-22 Ethicon, Inc. Alkyd-lactone copolymers for medical applications
WO2006013963A1 (fr) * 2004-08-05 2006-02-09 Hisamitsu Pharmaceutical Co., Inc. Preparation externe pour les ongles
US7005136B2 (en) 2002-03-29 2006-02-28 Ethicon, Inc. Bone replacement materials utilizing bioabsorbable liquid polymers
US7030127B2 (en) 2001-06-29 2006-04-18 Ethicon, Inc. Composition and medical devices utilizing bioabsorbable polymeric waxes
US7034037B2 (en) 2001-06-29 2006-04-25 Ethicon, Inc. Compositions and medical devices utilizing bioabsorbable polymeric waxes and rapamycin
US7101566B2 (en) 2002-06-28 2006-09-05 Ethicon, Inc. Polymer coated microparticles for sustained release
US7326426B2 (en) 2002-03-29 2008-02-05 Ethicon, Inc. Compositions and medical devices utilizing bioabsorbable liquid polymers
US8697753B1 (en) 2013-02-07 2014-04-15 Polichem Sa Method of treating onychomycosis
WO2014104149A1 (fr) * 2012-12-28 2014-07-03 大正製薬株式会社 Préparation pour application sur la peau

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6143794A (en) * 1998-04-17 2000-11-07 Bertek Pharmaceuticals, Inc. Topical formulations for the treatment of nail fungal diseases
WO2007102242A1 (fr) 2006-03-08 2007-09-13 Nihon Nohyaku Co., Ltd. Composition pharmaceutique externe
NZ571818A (en) 2006-03-08 2011-10-28 Nihon Nohyaku Co Ltd External pharmaceutical composition comprising luliconazole and an alpha-hydroxycarboxylic acid such as lactic acid, glycolic acid or malic acid.
US8058303B2 (en) 2006-03-08 2011-11-15 Nihon Nohyaku Co, Ltd Pharmaceutical composition for external use
JP5097363B2 (ja) * 2006-06-05 2012-12-12 小林製薬株式会社 抗真菌組成物
WO2009031642A1 (fr) 2007-09-05 2009-03-12 Pola Pharma Inc. Composition pharmaceutique
EP2191827B1 (fr) 2007-09-05 2013-10-30 Pola Pharma Inc. Composition antifongique
KR20100068271A (ko) 2007-09-05 2010-06-22 가부시키가이샤 폴라 파마 항진균 의약 조성물
JP5319950B2 (ja) 2008-04-08 2013-10-16 帝國製薬株式会社 塩酸ブテナフィン含有水性貼付剤
CN102387786B (zh) 2009-04-09 2015-09-09 宝丽制药股份有限公司 抗真菌药物组合物
JP5688405B2 (ja) 2009-04-09 2015-03-25 株式会社ポーラファルマ 抗真菌医薬組成物
US8952044B2 (en) 2009-08-25 2015-02-10 Pola Pharma Inc. Antimycotic pharmaceutical composition
US10898470B1 (en) 2019-08-13 2021-01-26 Sato Pharmaceutical Co., Ltd. Pharmaceutical composition containing antifungal agent as active ingredient

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58162514A (ja) * 1982-03-19 1983-09-27 Sumitomo Chem Co Ltd 外用ゲル製剤
JPH01110620A (ja) * 1987-10-21 1989-04-27 Nissan Chem Ind Ltd 抗真菌剤組成物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58162514A (ja) * 1982-03-19 1983-09-27 Sumitomo Chem Co Ltd 外用ゲル製剤
JPH01110620A (ja) * 1987-10-21 1989-04-27 Nissan Chem Ind Ltd 抗真菌剤組成物

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7030127B2 (en) 2001-06-29 2006-04-18 Ethicon, Inc. Composition and medical devices utilizing bioabsorbable polymeric waxes
US7034037B2 (en) 2001-06-29 2006-04-25 Ethicon, Inc. Compositions and medical devices utilizing bioabsorbable polymeric waxes and rapamycin
US7326426B2 (en) 2002-03-29 2008-02-05 Ethicon, Inc. Compositions and medical devices utilizing bioabsorbable liquid polymers
US7005136B2 (en) 2002-03-29 2006-02-28 Ethicon, Inc. Bone replacement materials utilizing bioabsorbable liquid polymers
AU2003204723B2 (en) * 2002-06-25 2007-12-06 Ethicon, Inc. Injectable microdispersions for medical applications
EP1374905A1 (fr) * 2002-06-25 2004-01-02 Ethicon, Inc. Compositions injectables pour applications médicales
KR101061383B1 (ko) 2002-06-25 2011-09-02 에디컨인코포레이티드 주사가능한 의료용 미세 분산액
US7101566B2 (en) 2002-06-28 2006-09-05 Ethicon, Inc. Polymer coated microparticles for sustained release
US6967234B2 (en) 2002-12-18 2005-11-22 Ethicon, Inc. Alkyd-lactone copolymers for medical applications
US6872799B2 (en) 2002-12-18 2005-03-29 Ethicon, Inc. Functionalized polymers for medical applications
WO2006013963A1 (fr) * 2004-08-05 2006-02-09 Hisamitsu Pharmaceutical Co., Inc. Preparation externe pour les ongles
WO2014104149A1 (fr) * 2012-12-28 2014-07-03 大正製薬株式会社 Préparation pour application sur la peau
US8697753B1 (en) 2013-02-07 2014-04-15 Polichem Sa Method of treating onychomycosis
US9107877B2 (en) 2013-02-07 2015-08-18 Polichem Sa Method of treating onychomycosis
US10172811B2 (en) 2013-02-07 2019-01-08 Polichem Sa Topical antifungal composition for treating onychomycosis

Also Published As

Publication number Publication date
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