KR20000045198A - Antifungal nail varnish - Google Patents

Antifungal nail varnish Download PDF

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Publication number
KR20000045198A
KR20000045198A KR1019980061749A KR19980061749A KR20000045198A KR 20000045198 A KR20000045198 A KR 20000045198A KR 1019980061749 A KR1019980061749 A KR 1019980061749A KR 19980061749 A KR19980061749 A KR 19980061749A KR 20000045198 A KR20000045198 A KR 20000045198A
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South Korea
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nail varnish
water
antifungal
forming polymer
film forming
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KR1019980061749A
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Korean (ko)
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이한구
김기탁
정상영
조진만
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김수지
대화제약 주식회사
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Priority to KR1019980061749A priority Critical patent/KR20000045198A/en
Publication of KR20000045198A publication Critical patent/KR20000045198A/en

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    • 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
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone

Abstract

PURPOSE: An antifungal nail varnish contains the followings: free terbinafine or its salt as an active ingredient; aqueous suspension film forming polymer in dispersed state; permeability enhancer; and organic solvent, water if required, or ordinary diluents which are used for preparing nail varnish. Consequently it shows an excellent permeability of drug. CONSTITUTION: A antifungal nail varnish comprises the followings: 0.0001-30 wt.% of terbinafine based on the total weight; 0.5-50 wt.% of aqueous suspension film forming polymer in dispersed state such as copolymer of ethylacrylate and methylmethacrylate, or water soluble ethylcellulose in dispersed state; 0.1-10 wt.% of permeability enhancer such as N,N-diethyl-meta-toluenamide, acetylalcohol, camphor, urea, salicylic acid or mixture thereof; conventional organic solvent for varnish. Resin such as toluensulfonamide form aldehyde can be added optionally for improving adhesion and better luster.

Description

항진균성 손톱 와니스Antifungal Nail Varnish

본 발명은 알릴아민계 항진균성 치료제인 다음 화학식 1의 터비나핀(Terbinafine)의 유리형 또는 그 염을 함유하는 항진균성 손톱 와니스에 관한 것이다.The present invention relates to an antifungal nail varnish containing an allylamine antifungal therapeutic agent free form or a salt thereof of Terbinafine of the formula (1).

화학식 1의 화합물인 터비나핀은 공지의 화합물로서 항진균 활성을 갖는다(Eur. Pat. Appl. 24587).Terbinapine, a compound of Formula 1, has antifungal activity as a known compound (Eur. Pat. Appl. 24587).

EP 0 515 312 A2에 따르면 필름 형성제로 4급암모늄 기능기를 갖는 아크릴-메타아크릴산의 알킬 에스테르 공중합체(상품명 : 유드라지트 RL-100), 메칠비닐에테르-말레인산 모노알킬 에스테르 공중합체, 폴리 비닐아세테이트 등과 같은 비 수용성의 고분자를 사용하여 손톱 와니스를 제조하였으나, 손톱에 대한 침투능력은 나타나 있지 않았다. 이 방법에서 사용된 필름 형성 고분자들은 비 수용성 화합물로서 소수성 약물과 친화성이 있어 손톱에 대한 침투 능력이 감소되는 단점이 있으리라 예상된다.According to EP 0 515 312 A2, alkyl ester copolymers of acryl-methacrylic acid having quaternary ammonium functional groups as film formers (trade name: Eudragit RL-100), methylvinylether-maleic acid monoalkyl ester copolymers, polyvinylacetate Nail varnish was prepared using a non-soluble polymer such as, but did not show the penetration ability to the nail. The film-forming polymers used in this method are non-aqueous compounds and are compatible with hydrophobic drugs, which may reduce the ability to penetrate nails.

이에 본 발명자들은 약물과 필름 형성 고분자들 간의 친화도를 고려하여 종래 기술의 단점을 보완하는 새로운 기제를 사용함으로써 손톱에 대한 침투 능력이 우수한 손톱 와니스를 제공하고자 하는 것이다.Therefore, the inventors of the present invention intend to provide a nail varnish having excellent penetrating ability to nail by using a new base that compensates for the disadvantages of the prior art in consideration of the affinity between the drug and the film-forming polymer.

본 발명자들은 터비나핀과, 유기용매와 필름 형성 고분자 물질 및, 투과 촉진제를 사용하여 와니스를 제조한 결과 손톱에 대한 높은 침투력을 나타냄을 확인하여 본 발명을 완성하였다.The present inventors completed the present invention by confirming that the varnish was produced using terbinafine, an organic solvent, a film-forming polymer material, and a permeation accelerator, and exhibited high penetration power to nails.

즉 본 발명의 목적은 약물과 필름형성 고분자들 간의 친화도를 고려하여, 유리형인 터비나핀이 소수성을 가지고 있으므로 수용성 현탁액 필름 형성 고분자를 사용하여 그 친화도를 감소시킴과 동시에 적절한 투과 촉진제를 사용하여 제조한, 손톱에 대한 침투능력이 우수한 손톱 와니스를 제공하는 것이다.That is, in view of the affinity between the drug and the film-forming polymer, the object of the present invention is to use a water-soluble suspension film-forming polymer to reduce the affinity and to use an appropriate permeation accelerator, since the terbinapine is hydrophobic. It is to provide a nail varnish excellent in penetration ability to the nail produced.

본 발명에 따른 항진균성 손톱 와니스는 활성성분으로서 터비나핀의 유리형 또는 그 염; 수용성 현탁액 필름 형성 고분자물질; 투과촉진제; 유기용매 및 필요에 따라 물, 기타 와니스 제조에 사용되는 통상의 부형제를 포함한다.Antifungal nail varnish according to the present invention is a free form or salt thereof of terbinafine as an active ingredient; Water soluble suspension film forming polymers; Permeation accelerators; Organic solvents and, if desired, conventional excipients used in the preparation of water and other varnishes.

활성성분인 터비나핀은 전체 조성물에 대하여 0.0001 - 30중량%의 비율로 사용할 수 있으며, 바람직하게는 0.01 - 10중량%이다.The active ingredient terbinafine may be used in an amount of 0.0001 to 30% by weight based on the total composition, and preferably 0.01 to 10% by weight.

수용성 현탁액 필름형성 고분자물질로서는 수용성 현탁액인 에칠 아크릴레이트와 메칠메타크릴레이트의 공중합체(상품명 : 유드라지트 NE-30D), 에칠셀롤로오스의 수용성현탁액 (상품명 : 아쿠아코트 ECD) 등이 사용된다. 이 수용성 고분자물질은 전체 중량에 대하여 0.5 - 50중량%의 비율로 사용할 수 있다.As the water-soluble suspension film-forming polymer material, a copolymer of ethyl acrylate and methyl methacrylate (trade name: Eudragit NE-30D), which is an aqueous suspension, and an aqueous suspension of ethylcellulose (trade name: Aquacoat ECD) are used. . This water-soluble high molecular material can be used in the ratio of 0.5-50 weight% with respect to the total weight.

에칠셀롤로오스의 수용성 현탁액이 사용된 경우 HPMC를 첨가하여 약물의 방출을 증가시킬 수 있으며, 에칠셀룰로오스에 대하여 0.1 - 50중량%를 사용할 수 있다.If an aqueous suspension of ethylcellulose is used, HPMC can be added to increase the release of the drug, and 0.1-50% by weight relative to ethylcellulose can be used.

투과촉진제로는 N,N-디에칠-메타-톨루엔아마이드, 세틸알코올, 요소, 캄파, 살리실산 등을 단독 또는 혼합물로서 사용할 수 있으며, 총 중량에 대하여 0.1 - 10중량%의 비율로 사용한다.As the permeation accelerator, N, N-diethyl-meth-tolueneamide, cetyl alcohol, urea, camphor, salicylic acid, or the like can be used alone or as a mixture, and is used in a ratio of 0.1 to 10% by weight based on the total weight.

유기용매로서는 통상의 와니스 제조에 사용되는 유기용매를 사용할 수 있으며, 예를 들면, 에틸아세테이트, 에탄올, 이소프로판올 등을 단독 또는 혼합용매로서 사용할 수 있다.As an organic solvent, the organic solvent used for normal varnish manufacture can be used, For example, ethyl acetate, ethanol, isopropanol, etc. can be used individually or as a mixed solvent.

또한, 본 발명에 따른 와니스의 접착력이나 광택을 향상시키기 위하여 톨루엔설폰아미드 포름알데히드 수지와 같은 수지류를 첨가하여 밀착성을 증가시키고 품성을 향상시킬 수 있다.In addition, in order to improve the adhesion and gloss of the varnish according to the present invention, resins such as toluenesulfonamide formaldehyde resin may be added to increase the adhesion and improve the properties.

하기 실시예는 전술한 본 발명을 설명하기 위한 것이며, 본 발명의 범위를 이에 제한하고자 함이 아니다.The following examples are intended to illustrate the invention described above, but are not intended to limit the scope of the invention thereto.

다음 각 실시예의 조성으로 통상의 와니스 제조방법에 따라 본 발명의 항진균성 손톱 와니스를 제조하였다.The antifungal nail varnish of the present invention was prepared according to the conventional varnish manufacturing method with the composition of the following Examples.

실시예 1Example 1

성분ingredient 사용량(중량%)Usage (% by weight) 터비나핀 유리형Terbinafin Glass 22 에칠아크릴레이트-메칠메타크릴레이트(2:1)공중합체Ethylacrylate-Methyl Methacrylate (2: 1) Copolymer 3030 에칠 아세테이트Ethyl acetate 1010 에탄올ethanol 3535 증류수Distilled water 55 이소프로판올Isopropanol 1818 합계 100100 total

실시예 2Example 2

성분ingredient 사용량(중량%)Usage (% by weight) 터비나핀 유리형Terbinafin Glass 22 에칠아크릴레이트-메칠메타크릴레이트(2:1)공중합체Ethylacrylate-Methyl Methacrylate (2: 1) Copolymer 3030 에칠 아세테이트Ethyl acetate 1010 에탄올ethanol 3535 증류수Distilled water 55 이소프로판올Isopropanol 1616 N,N-디에칠-메타-톨루엔아마이드N, N-Diethyl-meth-tolueneamide 22 합계 100100 total

실시예 3Example 3

성분ingredient 사용량(중량%)Usage (% by weight) 터비나핀 유리형Terbinafin Glass 22 에칠아크릴레이트-메칠메타크릴레이트(2:1)공중합체Ethylacrylate-Methyl Methacrylate (2: 1) Copolymer 3030 에칠 아세이트Ethyl Acetate 1010 에탄올ethanol 3535 증류수Distilled water 55 이소프로판올Isopropanol 1616 세칠 알코올Flush alcohol 22 합계 100100 total

실시예 4Example 4

성분ingredient 사용량(중량%)Usage (% by weight) 터비나핀 유리형Terbinafin Glass 22 에칠아크릴레이트-메칠메타크릴레이트(2:1)공중합체Ethylacrylate-Methyl Methacrylate (2: 1) Copolymer 3030 에칠 아세테이트Ethyl acetate 1010 에탄올ethanol 3535 증류수Distilled water 55 이소프로판올Isopropanol 1616 요소Element 22 합계 100100 total

실시예 5Example 5

성분ingredient 사용량(중량%)Usage (% by weight) 터비나핀 유리형Terbinafin Glass 22 에칠셀롤로오스의 수용성현탁액Aqueous Suspension of Ethyl Cellulose 55 HPMCHPMC 1One 톨루엔설폰아미드 포름알데히드 수지Toluenesulfonamide Formaldehyde Resin 55 에틸 아세테이트Ethyl acetate 2626 에탄올ethanol 33 이소프로판올Isopropanol 5656 캄파Kampa 22 합계 100100 total

실시예 6Example 6

성분ingredient 사용량(중량%)Usage (% by weight) 터비나핀 유리형Terbinafin Glass 22 에칠셀롤로오스의 수용성현탁액Aqueous Suspension of Ethyl Cellulose 55 HPMCHPMC 1One 톨루엔설폰아미드 포름알데히드 수지Toluenesulfonamide Formaldehyde Resin 55 에틸 아세테이트Ethyl acetate 2626 에탄올ethanol 33 이소프로판올Isopropanol 5454 캄파Kampa 22 N,N-디에칠-메타-톨루엔아마이드N, N-Diethyl-meth-tolueneamide 22 합계 100100 total

실시예 7Example 7

성분ingredient 사용량(중량%)Usage (% by weight) 터비나핀 유리형Terbinafin Glass 22 에칠셀롤로오스의 수용성현탁액Aqueous Suspension of Ethyl Cellulose 55 HPMCHPMC 1One 톨루엔설폰아미드 포름알데히드 수지Toluenesulfonamide Formaldehyde Resin 55 에틸 아세테이트Ethyl acetate 2626 에탄올ethanol 33 이소프로판올Isopropanol 5454 캄파Kampa 22 세칠 알코올Flush alcohol 22 합계 100100 total

실시예 8Example 8

성분ingredient 사용량(중량%)Usage (% by weight) 터비나핀 유리형Terbinafin Glass 22 에칠셀롤로오스의 수용성현탁액Aqueous Suspension of Ethyl Cellulose 55 HPMCHPMC 1One 톨루엔설폰아미드 포름알데히드 수지Toluenesulfonamide Formaldehyde Resin 55 에틸 아세테이트Ethyl acetate 2626 에탄올ethanol 33 이소프로판올Isopropanol 5454 캄파Kampa 22 요소Element 22 합계 100100 total

실험예 : 손톱 침투 효능 실험Experimental Example: Nail Penetration Efficacy Experiment

손발톱에 대한 침투효능 시험은 돼지 발톱(1cm2)에 네일라카를 50mg/cm2의 농도로 적용하였다. 그 적용시기는 1-7일간 1일1회 연속 도포하였으며, 네일라카의 재거는 60% 아세톤/증류수 용액으로 제거하였다. 7일째 도포한 후 도포된 네일락카를 제거하였다. 각각에 대하여 아세톤으로 추출한 후, 침투된 약물의 농도를 고속 액체 크로마토그라피법에 의해 측정하였다. 그 결과 표 1에서와 같다.Penetration efficacy test for nails was applied to pig claws (1cm 2 ) at a concentration of 50mg / cm 2 . The application time was applied once a day for 1-7 days, Jailaka jagger was removed with 60% acetone / distilled water solution. After seven days of application, the applied nail lacquer was removed. After extraction with acetone for each, the concentration of infiltrated drug was measured by high performance liquid chromatography. The results are shown in Table 1.

표 1. 네일라카의 돼지발톱에 대한 침투 효능 실험 (7일후)Table 1. Experiment of Penetrating Efficacy of Pig Lacquer on Pig Claw (After 7 Days)

추출량(μg)Extraction amount (μg) 침투율(%)Penetration rate (%) 실시예 1Example 1 40.1640.16 4.024.02 실시예 2Example 2 51.3251.32 5.135.13 실시예 3Example 3 46.5946.59 4.664.66 실시예 4Example 4 49.2349.23 4.924.92 실시예 5Example 5 48.7148.71 4.874.87 실시예 6Example 6 59.7859.78 5.985.98 실시예 7Example 7 52.1652.16 5.225.22 실시예 8Example 8 56.0756.07 5.705.70

본 발명은, 기존의 비 수용성 필름형성 고분자와는 달리 수용성의 필름형태 고분자를 사용하고, 또한 투과 촉진제를 사용하여 손톱에 대한 침투 능력이 우수한 항진균성 손톱 와니스를 제공한다.The present invention provides an antifungal nail varnish having excellent water permeability to nails by using a water-soluble film-type polymer and using a permeation accelerator, unlike conventional non-water-soluble film-forming polymers.

Claims (6)

항진균제로서 터비나핀의 유리형 또는 그 염; 수용성 현탁액 필름 형성 고분자물질; 투과 촉진제; 유기용매 및 통상의 와니스 제조용 부형제를 함유하는 항진균성 손톱 와니스.Free form or salt thereof of terbinafine as an antifungal agent; Water soluble suspension film forming polymers; Permeation promoter; An antifungal nail varnish containing an organic solvent and excipients for the manufacture of conventional varnishes. 제 1항에 있어서, 터비나핀이 0.001 - 30 중량%인 것을 특징으로 하는 손톱 와니스.2. Nail varnish according to claim 1, wherein turbinafin is 0.001-30 wt%. 제 1항에 있어서, 수용성 현탁액 필름 형성 고분자물질이 에칠아크릴레이트와 메칠메타크릴레이트의 공중합체 또는 에칠셀룰로오스인 것을 특징으로 하는 항진균성 손톱 와니스.The antifungal nail varnish according to claim 1, wherein the water-soluble suspension film forming polymer is a copolymer of ethyl acrylate and methyl methacrylate or ethyl cellulose. 제 1항 또는 3항에 있어서, 수용성 현탁액 필름 형성 고분자물질이 총 중량에 대해 0.5 - 50중량%인 것을 특징으로 하는 손톱 와니스.4. Nail varnish according to claim 1 or 3, wherein the water-soluble suspension film forming polymer is 0.5 to 50% by weight based on the total weight. 제 1항 또는 3항에 있어서, 수용성 필름형성 고분자물질로서 에칠셀롤로오스에 수용성 고분자 물질인 하이드록시 프로필 메칠 셀룰로오스(HPMC)를 0.1 - 50% 를 추가한 것을 특징으로 하는 항진균성 손톱 와니스.The antifungal nail varnish according to claim 1 or 3, wherein 0.1-50% of hydroxypropyl methyl cellulose (HPMC), which is a water-soluble polymer, is added to ethylcellulose as a water-soluble film-forming polymer. 제 1항에 있어서, 투과 촉진제로서 N,N-디에칠-메타-돌루엔아마이드, 세칠알코올, 요소, 캄파를 단독 또는 혼합물로서 총 중량에 대해 각각 0.1 - 10중량% 비율로 사용함을 특징으로 하는 손톱 와니스.The method according to claim 1, characterized in that N, N-dimethyl-meth-doluenamide, cetyl alcohol, urea, camphor, alone or as a mixture, are used at a ratio of 0.1 to 10% by weight relative to the total weight, respectively. Nail varnish.
KR1019980061749A 1998-12-30 1998-12-30 Antifungal nail varnish KR20000045198A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011019317A1 (en) * 2009-08-13 2011-02-17 Moberg Derma Ab Compositions and methods for treating fungal infection of the nail
WO2012070798A2 (en) * 2010-11-24 2012-05-31 Yuhan Corporation Topical antifungal composition comprising terbinafine or its salt

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011019317A1 (en) * 2009-08-13 2011-02-17 Moberg Derma Ab Compositions and methods for treating fungal infection of the nail
WO2012070798A2 (en) * 2010-11-24 2012-05-31 Yuhan Corporation Topical antifungal composition comprising terbinafine or its salt
WO2012070798A3 (en) * 2010-11-24 2012-08-09 Yuhan Corporation Topical antifungal composition comprising terbinafine or its salt

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