JP2005029502A - Antifungal agent composition - Google Patents
Antifungal agent composition Download PDFInfo
- Publication number
- JP2005029502A JP2005029502A JP2003196089A JP2003196089A JP2005029502A JP 2005029502 A JP2005029502 A JP 2005029502A JP 2003196089 A JP2003196089 A JP 2003196089A JP 2003196089 A JP2003196089 A JP 2003196089A JP 2005029502 A JP2005029502 A JP 2005029502A
- Authority
- JP
- Japan
- Prior art keywords
- antifungal
- antifungal agent
- terbinafine
- chloride
- allylamine
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 229940121375 antifungal agent Drugs 0.000 title claims abstract description 22
- 239000003429 antifungal agent Substances 0.000 title claims abstract description 20
- 239000000203 mixture Substances 0.000 title abstract description 9
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 claims abstract description 23
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 claims description 20
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 11
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 10
- 229960001950 benzethonium chloride Drugs 0.000 claims description 9
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 claims description 9
- 239000012871 anti-fungal composition Substances 0.000 claims description 8
- 230000000855 fungicidal effect Effects 0.000 claims description 7
- 239000000417 fungicide Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 229960002722 terbinafine Drugs 0.000 claims description 7
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
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Classifications
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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
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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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
Description
【0001】
【発明の属する技術分野】
本発明は、抗真菌剤組成物に関する。さらに、詳しくはアリルアミン系抗真菌剤の抗真菌力が増強された抗真菌剤組成物に関する。
【0002】
【従来の技術】
テルビナフィンは、我が国で現在汎用されている抗真菌剤の一つであり、アリルアミン系抗真菌剤に分類され、従来のイミダゾール系、チオカルバメート系、ベンジルアミン系、モルホリン系とは異なる新しい構造を有する。作用機序は真菌細胞膜エルゴステロールの生合成の阻害にあり、真菌細胞内のスクアレンエポキシダーゼを選択的に阻害し、スクアレンの蓄積およびエルゴステロール含量の低下をもたらし、強い抗真菌活性を示す(非特許文献1参照)。テルビナフィンは白癬菌属をはじめ、カンジダ属、クリプトコッカス属、アスペルギルス属、ペニシリウム属などの病原性真菌に対し幅広い抗菌スペクトルをもち、特に皮膚糸状菌に対するMIC値は非常に低い(非特許文献2参照)。
【0003】
このようなテルビナフィンの優れた抗真菌力を利用するために、抗ヒスタミン剤、テルペン化合物および尿素を配合し、ビナフィンの皮膚浸透性や皮膚滞留性を高めた組成物やサリチル酸メチル等の添加剤を配合し、表皮角質層への浸透を促進させた組成物が知られているが、テルビナフィンの抗真菌力そのものを向上させる効果は得られていない(特許文献1,2参照)。
【0004】
また、水虫は一般的に完全に治癒することが難しいことから、長期間薬剤を塗布し続ける必要があるが、患者の多くは冬場に菌の活動が緩和になると水虫の症状が治まることから、自己判断で薬剤塗布を中断してしまい、薬剤の治療効果を十分発揮することができないでいる。
【0005】
したがって短期間の塗布で優れた効果を現す抗真菌剤を提供することができれば水虫の治療に大きな効果を発揮することが期待できるが、従来十分満足できるものは無かった。
【0006】
【非特許文献1】山口 英世著、「病原真菌と真菌症」株式会社南山堂、84−85、1999年
【非特許文献2】真菌誌 第32巻 第4号 平成3年 323−332
【特許文献1】特開2002−284702号
【特許文献2】特開平08− 20527号
【0007】
【発明が解決しようとする課題】
本発明は、短期間の塗布で水虫の治療を可能とする、優れた効力を有する抗真菌剤組成物の提供を目的とする。
【0008】
【課題を解決するための手段】
本発明者らは、白癬菌属に効力を有する抗真菌剤について種々検討した結果、抗真菌剤としてアリルアミン系抗真菌剤と四級アンモニウム塩型殺菌剤を同時に配合することにより、優れた抗真菌効果を発揮することを見出し、本発明を完成した。
【0009】
すなわち、本発明は、(1)アリルアミン系抗真菌剤および4級アンモニウム塩型殺菌剤を配合することを特徴とする抗真菌剤組成物、(2)アリルアミン系抗真菌剤がテルビナフィン及びその塩類から選ばれる1種である(1)に記載の抗真菌剤組成物、(3)4級アンモニウム塩型殺菌剤が塩化ベンザルコニウム、塩化ベンゼトニウム、塩化デカリニウムからなる群より選ばれる化合物の一種又は二種以上である(1)又は(2)に記載の抗真菌剤組成物、を提供するものである。
【0010】
【発明の実施の形態】
本発明で配合されるアリルアミン系抗真菌剤としては、その化学構造中にアリルアミン系骨格を有するものであればよいが、テルビナフィンが好ましい。このものの塩としては、ナフタレン環に結合している置換アミノ酸基と塩を形成するものであれば、特段の限定無く適用でき、例えば、塩酸塩、硝酸塩、硫酸塩等の鉱酸塩、クエン酸塩、シュウ酸塩、コハク酸塩などの有機酸塩などが好ましく、塩酸塩が特に好ましい。
【0011】
また、4級アンモニウム型殺菌剤としては、カチオン界面活性剤で4級アンモニウム塩に属するものであればよく、本発明で好ましいものは、塩化ベンザルコニウム、塩化ベンゼトニウム、塩化デカリニウムなどが挙げられる。
【0012】
本発明において配合されるアリルアミン系抗真菌剤は、抗真菌効果が得られる有効量であればよく、例えば、塩酸テルビナフィンを配合する場合には、組成物全体(エアゾールの場合は原液中)中0.2〜2質量%であり、好ましくは0.5〜1.5質量%である。
【0013】
4級アンモニウム型殺菌剤の配合量はその成分及び配合される抗真菌剤により異なり、例えば、塩酸テルビナフィンを上記の範囲で配合する場合には、塩化ベンザルコニウムの配合量は、0.01 〜1質量%、好ましくは0.02〜0.5質量%、塩化ベンゼトニウムの配合量は0.05〜2質量%、好ましくは0.1〜1質量%、塩化デカリニウムの配合量は0.05〜2質量%、好ましくは0.1〜1質量%である。
【0014】
本発明の組成物は、必要に応じて通常の添加剤などを混合して常法により、液剤、ローション剤、乳剤、チンキ剤、軟膏剤、クリーム剤、水性ゲル剤、油性ゲル剤、エアゾール剤、パウダー剤などの外用製剤とすることができる。
【0015】
本発明において配合できる成分としては、プロピレングリコール、1,3−ブチレングリコール、グリセリン、エタノール、マクロゴール類などの水溶性成分、アジピン酸ジイソプロピル、ステアリルアルコール、セタノール、スクワラン、中鎖トリグリセライドなどの油性成分、カルボキシビニルポリマー、メチルセルロース、エチルセルロースなどの高分子、クエン酸、水酸化ナトリウム、ジイソプロパノールアミンなどのpH調整剤、ジブチルヒドロキシトルエン(BHT)、ブチルヒドロキシアニソール(BHA)、α−トコフェロール、エリソルビン酸、ピロ亜硫酸ナトリウムなどの抗酸化剤、ポリオキシエチレン硬化ヒマシ油、ソルビタンモノステアレート、ソルビタンモノパルミテート、グリセリンモノステアレート、ソルビタンモノラウレート、ポリオキシエチレンポリオキシプロピレンブロックコポリマー、ポリソルベート類、ラウリル硫酸ナトリウム、ショ糖脂肪酸エステル、レシチンなどの界面活性剤、EDTA−2Naなどの安定化剤があげられる。なお、これまでに記載した添加物については何ら限定されるものではない。
【0016】
【発明の効果】
本発明により、アリルアミン系抗真菌剤の抗真菌作用をより高めることができたことから、皮膚糸状菌に対して極めて効力の強い抗真菌剤を提供することが可能になった。
【0017】
【実施例】
以下実施例および試験例により、本発明を詳細に説明する。
実施例1
(クリーム)
塩酸テルビナフィン 1.0g
塩化ベンザルコニウム 0.05g
リドカイン 2.0g
グリチルリチン酸二カリウム 0.5g
l−メントール 1.0g
ポリオキシエチレンソルビタンモノステアレート 4.0g
ソルビタンモノステアレート 2.0g
1,3−ブチレングリコール 15.0g
中鎖脂肪酸トリグリセリド 15.0g
グリセリンモノステアレート 25.0g
EDTA−2Na 0.1g
精製水 全100g
水相成分(1,3−ブチレングリコール、塩化ベンザルコニウム、
EDTA−2Na、精製水)および油層成分(塩酸テルビナフィン、リドカイン、l−メントール、ソルビタンモノステアレート、ポリオキシエチレンソルビタンモノステアレート、中鎖脂肪酸トリグリセリド、グリセリンモノステアレート)をそれぞれ加温後混合し、通常の方法でクリーム100gを製造した。
【0018】
実施例2
(ゲルクリーム)
塩酸テルビナフィン 1.0g
塩化ベンゼトニウム 0.5g
リドカイン 2.0g
ポリオキシエチレンソルビタンモノステアレート 1.0g
プロピレングリコール 10.0g
中鎖脂肪酸トリグリセリド 5.0g
ステアリルアルコール 1.0g
カルボキシビニルポリマー 0.5g
ジイソプロパノールアミン 適量
EDTA−2Na 0.1g
精製水 全100g
油相成分(塩酸テルビナフィン、リドカイン、ポリオキシエチレンソルビタンモノステアレート、中鎖脂肪酸トリグリセリド、ステアリルアルコール)を加温溶解し、室温まで冷却した。ついで、水、プロピレングリコールにカルボキシビニルポリマーを溶解し、室温で放置し、カルボキシビニルポリマーを膨潤させた。これに水に溶解した塩化ベンゼトニウムおよび油相成分を加え乳化後、水に溶解したジイソパノールアミンおよびEDTA−2Naを添加し、ゲルクリームを製造した。
【0019】
実施例3
(ローション)
塩酸テルビナフィン 1.0g
塩化デカリニウム 0.5g
グリチルリチン酸二カリウム 0.5g
l−メントール 1.0g
ポリエチレングリコール400 20.0g
エタノール 50.0g
精製水 全100mL
上記処方で、常法によりローション剤を製造した。
【0020】
実施例4
(エアゾール剤)
原液:
塩酸テルビナフィン 1.0g
塩化ベンザルコニウム 0.05g
グリチルリチン酸二カリウム 0.5g
エタノール 50.0g
精製水 全100mL
噴射剤:
DME 100mL
エタノール、精製水の基剤に他の原液成分を溶解して原液を製造した。容器に充填後、バルブを装着し、噴射剤を充填してエアゾール剤を製造した。
【0021】
試験例1
塩酸テルビナフィンと各検体の組み合わせによりFICインデックス(Fractional Inhibitory Concentration index)を測定し、相加・相乗効果を測定した。
検体として以下の成分を用いた。
検体1:塩化ベンザルコニウム
検体2:塩化ベンゼトニウム
試験菌株
Trichophyton mentagrophytes(臨床分離株)
Trichophyton rubrum(臨床分離株)。
【0022】
(試験方法)
感受性試験は日本医真菌学会(標準化委員会)提案微量液体希釈法にて行った。感受性測定用培地として、0.165M MOPS−RPMI1640を用いた。
薬剤を含む培地に約105分生子/mLに調製した菌液を接種、27℃、にて最長4日間培養した。抗菌力の判定は発育コントロールが明らかに赤変した時点で目視にて行った。陰性コントロールと同様の青色を示すウエルの最小濃度をMIC値(最小発育阻止濃度、μg/mL)とした。チェッカーボード法によりFICインデックス(Fractional Inhibitory Concentration index)を算出した。
【0023】
【式1】算出式;
判定は、2より大きいものを拮抗作用、2以下〜1より大きいものを相加作用、1以下のものを相乗効果として併用効果の判定をした。
【0024】
得られたFICインデックスの結果を表1および2に示した。
【表1】塩酸テルビナフィンと塩化ベンザルコニウムの併用時における併用効果
【0025】
【表2】塩酸テルビナフィンと塩化ベンゼトニウムの併用時における併用効果
表1および2から明らかなように、塩酸テルビナフィンと塩化ベンザルコニウム、塩酸テルビナフィンと塩化ベンゼトニウムの併用は水虫の代表的な菌種に対して相乗効果を有することがわかった。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an antifungal composition. More specifically, the present invention relates to an antifungal composition in which the antifungal activity of the allylamine antifungal agent is enhanced.
[0002]
[Prior art]
Terbinafine is one of the antifungal agents currently widely used in Japan and is classified as an allylamine antifungal agent, and has a new structure different from conventional imidazole, thiocarbamate, benzylamine, and morpholine. . The mechanism of action is to inhibit the biosynthesis of fungal cell membrane ergosterol, which selectively inhibits squalene epoxidase in fungal cells, leading to accumulation of squalene and a decrease in ergosterol content, showing strong antifungal activity (non- Patent Document 1). Terbinafine has a broad antibacterial spectrum against pathogenic fungi such as Candida spp., Candida spp., Cryptococcus spp., Aspergillus spp., Penicillium spp., And particularly has a very low MIC for dermatophytes (see Non-Patent Document 2). .
[0003]
In order to utilize the superior antifungal power of terbinafine, an antihistamine, a terpene compound and urea are blended, and a composition that enhances skin penetration and skin retention of binafine and an additive such as methyl salicylate are blended. A composition that promotes penetration into the epidermal stratum corneum is known, but the effect of improving the antifungal power of terbinafine itself has not been obtained (see Patent Documents 1 and 2).
[0004]
In addition, since athlete's foot is generally difficult to heal completely, it is necessary to continue to apply the drug for a long time, but since most of the patients' fungus activity is eased in winter, athlete's foot symptoms will be cured, The drug application is interrupted by self-judgment, and the therapeutic effect of the drug cannot be fully exhibited.
[0005]
Therefore, if an antifungal agent that exhibits an excellent effect in a short period of time can be provided, it can be expected to exert a great effect on the treatment of athlete's foot, but there has been no satisfactory one in the past.
[0006]
[Non-Patent Document 1] Hideyo Yamaguchi, “Pathogenic Fungi and Mycosis”, Nanzan-do Co., Ltd., 84-85, 1999 [Non-Patent Document 2] Mycology Journal, Vol. 32, No. 4, 323-332
[Patent Document 1] JP-A No. 2002-284702 [Patent Document 2] JP-A No. 08-20527
[Problems to be solved by the invention]
An object of the present invention is to provide an antifungal agent composition having excellent efficacy that enables treatment of athlete's foot with a short-term application.
[0008]
[Means for Solving the Problems]
As a result of various studies on antifungal agents having an effect on the genus Trichoderma, the present inventors have obtained an excellent antifungal effect by simultaneously combining an allylamine antifungal agent and a quaternary ammonium salt fungicide as an antifungal agent. The present invention was completed by finding out that the effect was exhibited.
[0009]
That is, the present invention provides (1) an antifungal composition comprising an allylamine antifungal agent and a quaternary ammonium salt type fungicide, and (2) the allylamine antifungal agent is derived from terbinafine and its salts. One or two of the compounds selected from the group consisting of benzalkonium chloride, benzethonium chloride, and decalinium chloride, wherein the antifungal composition according to (1), which is one selected, and (3) a quaternary ammonium salt type fungicide The antifungal composition according to (1) or (2), which is a species or more, is provided.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
The allylamine antifungal agent to be blended in the present invention is not particularly limited as long as it has an allylamine skeleton in its chemical structure, but terbinafine is preferable. As a salt of this, as long as it forms a salt with a substituted amino acid group bonded to the naphthalene ring, it can be applied without particular limitation. For example, mineral salts such as hydrochloride, nitrate, sulfate, citric acid, etc. Organic salts such as salts, oxalates, and succinates are preferable, and hydrochlorides are particularly preferable.
[0011]
The quaternary ammonium type fungicide may be any cationic surfactant that belongs to a quaternary ammonium salt, and preferred examples of the present invention include benzalkonium chloride, benzethonium chloride, and decalinium chloride.
[0012]
The allylamine antifungal agent blended in the present invention may be an effective amount capable of obtaining an antifungal effect. For example, when terbinafine hydrochloride is blended, 0 in the whole composition (in the case of an aerosol, in a stock solution). .2 to 2% by mass, preferably 0.5 to 1.5% by mass.
[0013]
The blending amount of the quaternary ammonium type fungicide varies depending on the component and the antifungal agent blended. For example, when blending terbinafine hydrochloride in the above range, the blending amount of benzalkonium chloride is 0.01 to 1% by mass, preferably 0.02 to 0.5% by mass, the amount of benzethonium chloride is 0.05 to 2% by mass, preferably 0.1 to 1% by mass, and the amount of decalinium chloride is 0.05 to 2% by mass, preferably 0.1-1% by mass.
[0014]
The composition of the present invention may be mixed with conventional additives as necessary, and in the usual manner, solution, lotion, emulsion, tincture, ointment, cream, aqueous gel, oily gel, aerosol Or a preparation for external use such as a powder.
[0015]
Ingredients that can be blended in the present invention include water-soluble ingredients such as propylene glycol, 1,3-butylene glycol, glycerin, ethanol, and macrogol, and oily ingredients such as diisopropyl adipate, stearyl alcohol, cetanol, squalane, and medium chain triglycerides. , Polymers such as carboxyvinyl polymer, methylcellulose, ethylcellulose, pH adjusters such as citric acid, sodium hydroxide, diisopropanolamine, dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), α-tocopherol, erythorbic acid, Antioxidants such as sodium pyrosulfite, polyoxyethylene hydrogenated castor oil, sorbitan monostearate, sorbitan monopalmitate, glycerin monostearate, sorbi Emissions monolaurate, polyoxyethylene polyoxypropylene block copolymers, polysorbates, sodium lauryl sulfate, sucrose fatty acid esters, surfactants such as lecithin, stabilizers such EDTA-2Na and the like. In addition, it does not limit at all about the additive described until now.
[0016]
【The invention's effect】
According to the present invention, since the antifungal action of the allylamine antifungal agent can be further enhanced, it is possible to provide an antifungal agent that is extremely effective against dermatophytes.
[0017]
【Example】
Hereinafter, the present invention will be described in detail by way of examples and test examples.
Example 1
(cream)
Terbinafine hydrochloride 1.0 g
Benzalkonium chloride 0.05g
Lidocaine 2.0g
Dipotassium glycyrrhizinate 0.5g
l-Menthol 1.0g
Polyoxyethylene sorbitan monostearate 4.0g
Sorbitan monostearate 2.0g
1,3-butylene glycol 15.0 g
Medium chain fatty acid triglyceride 15.0g
Glycerin monostearate 25.0g
EDTA-2Na 0.1g
100g of purified water
Aqueous phase components (1,3-butylene glycol, benzalkonium chloride,
EDTA-2Na, purified water) and oil layer components (terbinafine hydrochloride, lidocaine, l-menthol, sorbitan monostearate, polyoxyethylene sorbitan monostearate, medium chain fatty acid triglyceride, glycerin monostearate) are heated and mixed. 100 g of cream was produced in the usual way.
[0018]
Example 2
(Gel cream)
Terbinafine hydrochloride 1.0 g
Benzethonium chloride 0.5g
Lidocaine 2.0g
Polyoxyethylene sorbitan monostearate 1.0g
Propylene glycol 10.0g
Medium chain triglyceride 5.0g
Stearyl alcohol 1.0g
Carboxy vinyl polymer 0.5g
Diisopropanolamine appropriate amount EDTA-2Na 0.1g
100g of purified water
The oil phase components (terbinafine hydrochloride, lidocaine, polyoxyethylene sorbitan monostearate, medium chain fatty acid triglyceride, stearyl alcohol) were dissolved by heating and cooled to room temperature. Next, the carboxyvinyl polymer was dissolved in water and propylene glycol and allowed to stand at room temperature to swell the carboxyvinyl polymer. Benzethonium chloride dissolved in water and an oil phase component were added to this to emulsify, and then diisopananolamine and EDTA-2Na dissolved in water were added to produce a gel cream.
[0019]
Example 3
(lotion)
Terbinafine hydrochloride 1.0 g
Decalinium chloride 0.5g
Dipotassium glycyrrhizinate 0.5g
l-Menthol 1.0g
Polyethylene glycol 400 20.0g
Ethanol 50.0g
100 mL of purified water
With the above formulation, a lotion preparation was produced by a conventional method.
[0020]
Example 4
(Aerosol)
Stock solution:
Terbinafine hydrochloride 1.0 g
Benzalkonium chloride 0.05g
Dipotassium glycyrrhizinate 0.5g
Ethanol 50.0g
100 mL of purified water
Propellant:
DME 100mL
Other stock solution components were dissolved in a base of ethanol and purified water to produce a stock solution. After filling the container, a valve was attached and a propellant was filled to produce an aerosol.
[0021]
Test example 1
The combination of terbinafine hydrochloride and each specimen was used to measure the FIC index (Fractional Inhibitory Concentration index), and the additive / synergistic effect was measured.
The following components were used as specimens.
Specimen 1: Benzalkonium chloride Specimen 2: Benzethonium chloride test strain Trichophyton mentagrophytes (clinical isolate)
Trichophyton rubrum (clinical isolate).
[0022]
(Test method)
The susceptibility test was performed by the micro liquid dilution method proposed by the Japanese Society for Medical Mycology (Standardization Committee). As a medium for measuring sensitivity, 0.165M MOPS-RPMI1640 was used.
The medium containing the drug was inoculated with a bacterial solution prepared to about 10 5 conidia / mL and cultured at 27 ° C. for a maximum of 4 days. The antibacterial activity was judged visually when the growth control was clearly red. The minimum concentration of wells exhibiting the same blue color as the negative control was defined as the MIC value (minimum growth inhibitory concentration, μg / mL). The FIC index (Fractional Inhibition Concentration index) was calculated by the checkerboard method.
[0023]
[Formula 1] Calculation formula;
Judgment of the combined effect was made by determining that the antagonistic effect was greater than 2, the additive effect was greater than 2 to 1, and the synergistic effect was 1 or less.
[0024]
The obtained FIC index results are shown in Tables 1 and 2.
[Table 1] Combined effects of terbinafine hydrochloride and benzalkonium chloride
[0025]
[Table 2] Combined effects of terbinafine hydrochloride and benzethonium chloride
As is clear from Tables 1 and 2, it was found that the combined use of terbinafine hydrochloride and benzalkonium chloride, or terbinafine hydrochloride and benzethonium chloride had a synergistic effect on representative species of athlete's foot.
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JP2003196089A JP2005029502A (en) | 2003-07-11 | 2003-07-11 | Antifungal agent composition |
JP2005511534A JP4692280B2 (en) | 2003-07-11 | 2004-07-09 | Antifungal composition |
PCT/JP2004/009808 WO2005004856A1 (en) | 2003-07-11 | 2004-07-09 | Antifungal composition |
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JP2006232853A (en) * | 2006-06-05 | 2006-09-07 | Kobayashi Pharmaceut Co Ltd | Antifungal composition |
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EP1900378A1 (en) * | 2006-08-31 | 2008-03-19 | Novartis AG | Pharmaceutical compositions for the treatment of fungal infections |
CN101467960B (en) * | 2007-12-29 | 2012-11-28 | 浙江康恩贝制药股份有限公司 | Terbinafine hydrochloride emulsifiable paste and preparation method thereof |
US7799056B2 (en) | 2007-12-31 | 2010-09-21 | Warsaw Orthopedic, Inc. | Bone fusion device and methods |
WO2015102850A2 (en) * | 2014-01-02 | 2015-07-09 | Cook Medical Technologies Llc | Compositions, devices and methods for treating infections |
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JP2002114680A (en) * | 2000-07-31 | 2002-04-16 | Nippon Nohyaku Co Ltd | Antifungal agent |
JP4899139B2 (en) * | 2000-08-10 | 2012-03-21 | 株式会社ポーラファルマ | Antifungal pharmaceutical composition |
JP2003055205A (en) * | 2001-08-09 | 2003-02-26 | Taisho Pharmaceut Co Ltd | Composition for alleviating fungal disease |
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