JP2006182733A - External preparation composition - Google Patents
External preparation composition Download PDFInfo
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- JP2006182733A JP2006182733A JP2004380216A JP2004380216A JP2006182733A JP 2006182733 A JP2006182733 A JP 2006182733A JP 2004380216 A JP2004380216 A JP 2004380216A JP 2004380216 A JP2004380216 A JP 2004380216A JP 2006182733 A JP2006182733 A JP 2006182733A
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- acid
- terbinafine hydrochloride
- composition
- mass
- polyol
- Prior art date
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- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims description 15
- 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 abstract description 41
- 229960000699 terbinafine hydrochloride Drugs 0.000 claims abstract description 38
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims abstract description 20
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 claims abstract description 16
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims abstract description 16
- 229920005862 polyol Polymers 0.000 claims abstract description 16
- 150000003077 polyols Chemical class 0.000 claims abstract description 16
- 150000007524 organic acids Chemical class 0.000 claims abstract description 12
- 229940058015 1,3-butylene glycol Drugs 0.000 claims abstract description 10
- 235000019437 butane-1,3-diol Nutrition 0.000 claims abstract description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 9
- 235000014655 lactic acid Nutrition 0.000 claims description 9
- 239000004310 lactic acid Substances 0.000 claims description 9
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-araboascorbic acid Natural products OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 claims description 5
- 235000015165 citric acid Nutrition 0.000 claims description 5
- 235000010350 erythorbic acid Nutrition 0.000 claims description 5
- 239000004318 erythorbic acid Substances 0.000 claims description 5
- 229940026239 isoascorbic acid Drugs 0.000 claims description 5
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- 235000011090 malic acid Nutrition 0.000 claims description 4
- 239000001630 malic acid Substances 0.000 claims description 4
- 238000013329 compounding Methods 0.000 claims description 3
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 235000012208 gluconic acid Nutrition 0.000 claims description 2
- 239000000174 gluconic acid Substances 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 238000012360 testing method Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 238000009472 formulation Methods 0.000 description 6
- 239000006210 lotion Substances 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 239000000443 aerosol Substances 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 4
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 4
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 4
- 229940043276 diisopropanolamine Drugs 0.000 description 4
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 4
- 229960004194 lidocaine Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000007928 solubilization Effects 0.000 description 4
- 238000005063 solubilization Methods 0.000 description 4
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- 229960000686 benzalkonium chloride Drugs 0.000 description 3
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229960002722 terbinafine Drugs 0.000 description 3
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 230000003381 solubilizing effect Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 239000012871 anti-fungal composition Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 201000009862 superficial mycosis Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- -1 tinctures Substances 0.000 description 1
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- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、外用剤組成物に関し、詳しくは塩酸テルビナフィンとポリオールを同時配合した時に生じる塩酸テルビナフィンの分解が抑制された外用抗真菌剤組成物に関する。 The present invention relates to an external preparation composition, and more particularly, to an external antifungal composition in which decomposition of terbinafine hydrochloride that occurs when terbinafine hydrochloride and a polyol are blended simultaneously is suppressed.
塩酸テルビナフィンは汎用されている抗真菌剤の一つであり、種々真菌症に有用であることが知られている。塩酸テルビナフィンは浅在性真菌症などの外用抗真菌剤として有用なものであるが、その性質は水に難溶性であり、可溶化等の製剤的工夫が必要となる。可溶化の手段としては、水、低級アルカノール（エタノール等）および水溶解性または水混和性非イオン表面活性剤を含み、アニオン系表面活性剤を含まないことを特徴とする技術（特許文献１）のように、エタノールと界面活性剤を用いる方法が開示されている。しかしながら、界面活性剤とアルコールの系で可溶化する方法は、皮膚刺激性の懸念があり、塩酸テルビナフィンの可溶化方法としては十分とはいえない。また、一般的な手法としてｐＨの調節により可溶化・安定化する手段もあるが、塩酸テルビナフィンと併用する薬物の溶解性および安定性の問題から、限られたｐＨ幅以外での可溶化・安定化は難しかった。 Terbinafine hydrochloride is one of the widely used antifungal agents and is known to be useful for various mycosis. Terbinafine hydrochloride is useful as an antifungal agent for external use such as superficial mycosis, but its properties are hardly soluble in water, and it requires formulation measures such as solubilization. As a solubilizing means, water, a lower alkanol (such as ethanol) and a water-soluble or water-miscible nonionic surfactant are included, and a technique that does not include an anionic surfactant (Patent Document 1) Thus, a method using ethanol and a surfactant is disclosed. However, the method of solubilization with a surfactant and alcohol system is concerned with skin irritation and is not sufficient as a method of solubilizing terbinafine hydrochloride. In addition, as a general method, there is a means to solubilize and stabilize by adjusting pH, but due to the problem of solubility and stability of the drug used in combination with terbinafine hydrochloride, solubilization / stabilization outside a limited pH range Conversion was difficult.
また、従来塩酸テルビナフィンおよびブチルヒドロキシトルエンを配合する処方は知られている（特許文献２，３）が、本願発明の構成は知られていない。 Moreover, the formulation which mix | blends terbinafine hydrochloride and butylhydroxytoluene conventionally is known (patent document 2, 3), However, The structure of this invention is not known.
本発明者らは塩酸テルビナフィンの可溶化のために、１,３-ブチレングリコールやポリエチレングリコールなどのポリオールを配合する検討を行った。しかし、塩酸テルビナフィンをポリオールにより可溶化すると塩酸テルビナフィンが分解して、経時的な塩酸テルビナフィンの含量が低下することがわかった。 The present inventors have studied to blend polyols such as 1,3-butylene glycol and polyethylene glycol for solubilization of terbinafine hydrochloride. However, it was found that when terbinafine hydrochloride is solubilized with a polyol, terbinafine hydrochloride is decomposed and the content of terbinafine hydrochloride with time decreases.
本発明は、難溶性の塩酸テルビナフィンを安定に溶解した外用組成物を提供することを目的とする。 An object of this invention is to provide the composition for external use which melt | dissolved the hardly soluble terbinafine hydrochloride stably.
本発明者らは、上記課題を解決するために種々検討した結果、塩酸テルビナフィン、ポリオール、ジブチルヒドロキシトルエンおよび有機酸を同時に配合することにより、塩酸テルビナフィンの分解が抑制され、安定な状態で溶解できることを見出し、本発明を完成した。 As a result of various studies to solve the above-mentioned problems, the present inventors have found that terbinafine hydrochloride, polyol, dibutylhydroxytoluene and organic acid are added at the same time, so that decomposition of terbinafine hydrochloride is suppressed and can be dissolved in a stable state. The present invention has been completed.
すなわち、本発明は、塩酸テルビナフィン、ポリオール、ジブチルヒドロキシトルエンおよび有機酸を配合したことを特徴とする外用組成物である。 That is, the present invention is an external composition characterized by blending terbinafine hydrochloride, polyol, dibutylhydroxytoluene, and an organic acid.
本発明において、塩酸テルビナフィンの配合量は、製剤全体（エアゾールの場合は原液中）の０．２〜２質量％であり、好ましくは０．５〜１．５質量％である。０．２質量％未満であると薬効が不十分になり、２質量％を超えて配合すると、安定に溶解した状態を保つのが難しくなるからである。 In the present invention, the blending amount of terbinafine hydrochloride is 0.2 to 2% by mass, preferably 0.5 to 1.5% by mass, based on the whole preparation (in the case of an aerosol, in a stock solution). This is because if it is less than 0.2% by mass, the medicinal effect becomes insufficient, and if it exceeds 2% by mass, it is difficult to maintain a stable dissolved state.
本発明において、配合するポリオールの種類としては、ポリエチレングリコール（マクロゴール）、プロピレングリコール、1,3-ブチレングリコール、グリセリンなどがあげられる。ポリオールの配合量は、多量に配合しすぎると、皮膚塗布時にべたつき、使用感が非常に悪くなるため、通常、製剤全体（エアゾールの場合は原液中）の５〜３０質量％であり、好ましくは１０〜２５質量％である。また、２種類以上のポリオールを混合して用いることもできる。本発明でテルビナフィン１質量部に対するポリオールの配合量は2.5〜30.0質量部が好ましい。 In the present invention, examples of the polyol to be blended include polyethylene glycol (macrogol), propylene glycol, 1,3-butylene glycol, glycerin and the like. The blending amount of the polyol is excessively blended when sticking to the skin and the feeling of use becomes very bad. Usually, it is 5 to 30% by mass of the whole preparation (in the stock solution in the case of aerosol), preferably 10 to 25% by mass. Also, two or more types of polyols can be mixed and used. In the present invention, the blending amount of the polyol with respect to 1 part by mass of terbinafine is preferably 2.5 to 30.0 parts by mass.
有機酸の種類としては、クエン酸、乳酸、リンゴ酸、エリソルビン酸、アルコルビン酸、グルコン酸、酒石酸などがあげられ、好ましくはクエン酸、乳酸、リンゴ酸またはエリソルビン酸である。 Examples of the organic acid include citric acid, lactic acid, malic acid, erythorbic acid, ascorbic acid, gluconic acid, and tartaric acid, and citric acid, lactic acid, malic acid, and erythorbic acid are preferable.
有機酸の配合量は０．０１〜５．０質量％であり、好ましくは０．０５〜３．０質量％である。また、２種類以上の有機酸を混合して用いることもできる。本発明でテルビナフィン１質量部に対する有機酸の配合量は0.01〜5.0質量部が好ましい。 The compounding amount of the organic acid is 0.01 to 5.0% by mass, preferably 0.05 to 3.0% by mass. Two or more kinds of organic acids can be mixed and used. In the present invention, the blending amount of the organic acid with respect to 1 part by mass of terbinafine is preferably 0.01 to 5.0 parts by mass.
ジブチルヒドロキシトルエンの配合量は０．０１〜３．０質量％であり、好ましくは、０．０５〜１．０質量％である。本発明ではテルビナフィン１質量部に対するジブチルヒドロキシトルエンの配合量は0.01〜3.0質量部が好ましい。 The compounding quantity of dibutylhydroxytoluene is 0.01-3.0 mass%, Preferably, it is 0.05-1.0 mass%. In the present invention, the blending amount of dibutylhydroxytoluene with respect to 1 part by mass of terbinafine is preferably 0.01 to 3.0 parts by mass.
本発明で用いる溶媒は通常の外用剤に使用されるものを用いることができるが塩酸テルビナフィンの溶解性と皮膚刺激性の点から含水エタノールが最も好ましい。 As the solvent used in the present invention, those used in usual external preparations can be used, but water-containing ethanol is most preferable from the viewpoint of solubility of terbinafine hydrochloride and skin irritation.
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、クリーム剤、水性ゲル剤、エアゾール剤などの外用製剤とすることができる。 The composition of the present invention may be mixed with conventional additives as necessary to prepare external preparations such as liquids, lotions, emulsions, tinctures, creams, aqueous gels, aerosols, etc. Can do.
本発明により塩酸テルビナフィンが安定に溶解することができた。 According to the present invention, terbinafine hydrochloride was able to be dissolved stably.
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。 Hereinafter, the present invention will be described in detail by way of examples and test examples.
（ローション）
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
ｌ-メントール １．０ｇ
ポリエチレングリコール４００ １０．０ｇ
エタノール ６０．０ｇ
ジブチルヒドロキシトルエン ０．０５ｇ
クエン酸 ２．０ｇ
精製水 全１００ｇ
上記処方で、常法によりローション剤を製造した。
(lotion)
Terbinafine hydrochloride 1.0 g
Benzalkonium chloride 0.05g
Dipotassium glycyrrhizinate 0.5g
l-Menthol 1.0g
Polyethylene glycol 400 10.0g
Ethanol 60.0g
Dibutylhydroxytoluene 0.05g
Citric acid 2.0g
100g of purified water
With the above formulation, a lotion preparation was produced by a conventional method.
（ローション）
塩酸テルビナフィン １．０ｇ
リドカイン ２．０ｇ
塩化デカリニウム ０．１ｇ
グリチルリチン酸二カリウム ０．５ｇ
ｌ-メントール １．０ｇ
１，３-ブチレングリコール ２０．０ｇ
エタノール ５０．０ｇ
ジブチルヒドロキシトルエン ０．０５ｇ
乳酸 ２．０ｇ
精製水 全１００ｇ
上記処方で、常法によりローション剤を製造した。
(lotion)
Terbinafine hydrochloride 1.0 g
Lidocaine 2.0g
Decalinium chloride 0.1g
Dipotassium glycyrrhizinate 0.5g
l-Menthol 1.0g
1,3-butylene glycol 20.0g
Ethanol 50.0g
Dibutylhydroxytoluene 0.05g
Lactic acid 2.0g
100g of purified water
With the above formulation, a lotion preparation was produced by a conventional method.
塩酸テルビナフィン １．０ｇ
リドカイン ２．０ｇ
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
ｌ-メントール １．０ｇ
１，３-ブチレングリコール ５．０ｇ
エタノール ６０．０ｇ
ジブチルヒドロキシトルエン ０．０５ｇ
乳酸 ２．０ｇ
精製水 全１００ｇ
上記処方で、常法によりローション剤を製造した。
Terbinafine hydrochloride 1.0 g
Lidocaine 2.0g
Benzalkonium chloride 0.05g
Dipotassium glycyrrhizinate 0.5g
l-Menthol 1.0g
1,3-butylene glycol 5.0 g
Ethanol 60.0g
Dibutylhydroxytoluene 0.05g
Lactic acid 2.0g
100g of purified water
With the above formulation, a lotion preparation was produced by a conventional method.
（ゲル剤）
塩酸テルビナフィン １．０ｇ
リドカイン ２．０ｇ
１，３-ブチレングリコール １５．０ｇ
カルボキシビニルポリマー １．０ｇ
ＥＤＴＡ−２Ｎａ ０．１ｇ
エタノール ４５．０ｇ
ジブチルヒドロキシトルエン ０．０５ｇ
乳酸 ２．０ｇ
ジイソプロパノールアミン 適量
精製水 全１００ｇ
水、１，３-ブチ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。これにエタノール、ジブチルヒドロキシトルエン、塩酸テルビナフィン、リドカイン、乳酸およびＥＤＴＡ−２Ｎａを添加した。さらにジイソプロパノールアミンを加え、製剤のｐＨを約８に調整し、ゲルを製造した。
(Gel agent)
Terbinafine hydrochloride 1.0 g
Lidocaine 2.0g
1,3-butylene glycol 15.0 g
Carboxyvinyl polymer 1.0g
EDTA-2Na 0.1g
Ethanol 45.0g
Dibutylhydroxytoluene 0.05g
Lactic acid 2.0g
Diisopropanolamine appropriate amount purified water 100g
The carboxyvinyl polymer was dissolved in water and 1,3-butylene glycol and allowed to stand at room temperature to swell the carboxyvinyl polymer. To this was added ethanol, dibutylhydroxytoluene, terbinafine hydrochloride, lidocaine, lactic acid and EDTA-2Na. Further, diisopropanolamine was added to adjust the pH of the preparation to about 8 to produce a gel.
（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
１，３ブチレングリコール ２０．０ｇ
エタノール ５０．０ｇ
ジブチルヒドロキシトルエン ０．０５ｇ
乳酸 ２．０ｇ
ジイソプロパノールアミン 適量
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後、ジイソプロパノールアミンにて製剤のｐＨを約８に調整し、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。
(Aerosol)
Stock solution:
Terbinafine hydrochloride 1.0 g
Benzalkonium chloride 0.05g
Dipotassium glycyrrhizinate 0.5g
1,3 butylene glycol 20.0g
Ethanol 50.0g
Dibutylhydroxytoluene 0.05g
Lactic acid 2.0g
Diisopropanolamine appropriate amount purified water 100mL
Propellant:
DME 100mL
The other stock solution components were dissolved in a base of ethanol and purified water, and then the pH of the preparation was adjusted to about 8 with diisopropanolamine to produce a stock solution. After filling the container, a valve was attached and a propellant was filled to produce an aerosol.
試験例１
塩酸テルビナフィンの安定性試験
（試験方法）
下記の処方で調製した溶液をガラスアンプルに充填し、塩酸テルビナフィンの安定性を５０℃、２ヶ月の過酷試験で評価した。塩酸テルビナフィンの定量値は液体クロマトグラフを用いて測定し、試験開始時の定量値を１００％として、算出した。処方を表１−１〜表１−３に、結果を図１〜３にそれぞれ示した。
Test example 1
Test for stability of terbinafine hydrochloride (test method)
A solution prepared according to the following formulation was filled in a glass ampule, and the stability of terbinafine hydrochloride was evaluated by a severe test at 50 ° C. for 2 months. The quantitative value of terbinafine hydrochloride was measured using a liquid chromatograph, and the quantitative value at the start of the test was calculated as 100%. The prescriptions are shown in Tables 1-1 to 1-3, and the results are shown in FIGS.
図１から明らかなように、塩酸テルビナフィンの含量はポリオール配合により低下した。しかし、そこにジブチルヒドロキシトルエンとエリソルビン酸を同時に配合することにより、改善が認められ、わずかな低下に留まった。この効果は、ジブチルヒドロキシトルエン、エリソルビン酸それぞれ単独では効果が十分ではなかった。 As is apparent from FIG. 1, the content of terbinafine hydrochloride was lowered by the blending of polyol. However, by adding dibutylhydroxytoluene and erythorbic acid at the same time, improvement was observed and only a slight decrease was observed. This effect was not sufficient with dibutylhydroxytoluene and erythorbic acid alone.
次に、図２および３に示したとおり、有機酸の種類を増やし、塩酸テルビナフィンの安定化効果を確認した結果、１，３−ブチレングリコールおよびポリエチレングリコール４００配合による塩酸テルビナフィンの不安定化は、有機酸（クエン酸、乳酸、リンゴ酸）とジブチルヒドロキシトルエンを同時に配合することにより、大きく改善した。なお、いずれのサンプルもｐＨは調整しており、ｐＨ調節による安定化ではないことは明らかである。 Next, as shown in FIGS. 2 and 3, as a result of increasing the type of organic acid and confirming the stabilizing effect of terbinafine hydrochloride, the destabilization of terbinafine hydrochloride by blending 1,3-butylene glycol and polyethylene glycol 400 is The organic acid (citric acid, lactic acid, malic acid) and dibutylhydroxytoluene were mixed at the same time, which greatly improved. In all samples, the pH is adjusted and it is clear that the pH is not stabilized.
本発明により塩酸テルビナフィンを安定に溶解することが可能になったので外用医薬品として有用である。 Since terbinafine hydrochloride can be stably dissolved by the present invention, it is useful as an external medicine.
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| WO2012107565A1 (en) * | 2011-02-11 | 2012-08-16 | Moberg Derma Ab | Novel antifungal composition |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002363070A (en) * | 2001-06-06 | 2002-12-18 | Yuutoku Yakuhin Kogyo Kk | Transdermal patch preparation |
| WO2003020250A1 (en) * | 2001-09-04 | 2003-03-13 | Trommsdorff Gmbh & Co. Kg Arzneimittel | Plaster for the treatment of dysfunctions and disorders of nail growth |
| JP2004035411A (en) * | 2002-06-28 | 2004-02-05 | Sato Pharmaceutical Co Ltd | External antifungal agent |
| JP2004203895A (en) * | 2004-04-12 | 2004-07-22 | Sato Pharmaceutical Co Ltd | Antifungal agent for external application |
| JP2005104924A (en) * | 2003-09-30 | 2005-04-21 | Kobayashi Pharmaceut Co Ltd | External pharmaceutical composition |
| JP2006131597A (en) * | 2004-11-09 | 2006-05-25 | Hisamitsu Pharmaceut Co Inc | Aerosol composition |
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002363070A (en) * | 2001-06-06 | 2002-12-18 | Yuutoku Yakuhin Kogyo Kk | Transdermal patch preparation |
| WO2003020250A1 (en) * | 2001-09-04 | 2003-03-13 | Trommsdorff Gmbh & Co. Kg Arzneimittel | Plaster for the treatment of dysfunctions and disorders of nail growth |
| JP2004035411A (en) * | 2002-06-28 | 2004-02-05 | Sato Pharmaceutical Co Ltd | External antifungal agent |
| JP2005104924A (en) * | 2003-09-30 | 2005-04-21 | Kobayashi Pharmaceut Co Ltd | External pharmaceutical composition |
| JP2004203895A (en) * | 2004-04-12 | 2004-07-22 | Sato Pharmaceutical Co Ltd | Antifungal agent for external application |
| JP2006131597A (en) * | 2004-11-09 | 2006-05-25 | Hisamitsu Pharmaceut Co Inc | Aerosol composition |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012107565A1 (en) * | 2011-02-11 | 2012-08-16 | Moberg Derma Ab | Novel antifungal composition |
| CN103384518A (en) * | 2011-02-11 | 2013-11-06 | 莫贝里制药公司 | Novel antifungal composition |
| KR20140025341A (en) * | 2011-02-11 | 2014-03-04 | 모베르그 파르마 아베 | Novel antifungal composition |
| JP2014508146A (en) * | 2011-02-11 | 2014-04-03 | モーベリ・ファルマ・エイビイ | Antifungal composition |
| US8952070B2 (en) | 2011-02-11 | 2015-02-10 | Moberg Pharma Ab | Antifungal composition |
| RU2587064C2 (en) * | 2011-02-11 | 2016-06-10 | Моберг Фарма Аб | Novel antifungal composition |
| KR101647545B1 (en) | 2011-02-11 | 2016-08-10 | 모베르그 파르마 아베 | Novel antifungal composition |
| US9561279B2 (en) | 2011-02-11 | 2017-02-07 | Moberg Pharma Ab | Antifungal composition |
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