CN1195550C - 外用剂 - Google Patents
外用剂 Download PDFInfo
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- CN1195550C CN1195550C CNB998151432A CN99815143A CN1195550C CN 1195550 C CN1195550 C CN 1195550C CN B998151432 A CNB998151432 A CN B998151432A CN 99815143 A CN99815143 A CN 99815143A CN 1195550 C CN1195550 C CN 1195550C
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- -1 2-ethylhexyl Chemical group 0.000 claims description 8
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 claims description 8
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- 150000001412 amines Chemical class 0.000 claims description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims description 4
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- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical group OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 3
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 3
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- NSOXQYCFHDMMGV-UHFFFAOYSA-N Tetrakis(2-hydroxypropyl)ethylenediamine Chemical compound CC(O)CN(CC(C)O)CCN(CC(C)O)CC(C)O NSOXQYCFHDMMGV-UHFFFAOYSA-N 0.000 claims description 2
- SLINHMUFWFWBMU-UHFFFAOYSA-N Triisopropanolamine Chemical compound CC(O)CN(CC(C)O)CC(C)O SLINHMUFWFWBMU-UHFFFAOYSA-N 0.000 claims description 2
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- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 claims 2
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- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 2
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- QJBZDBLBQWFTPZ-UHFFFAOYSA-N pyrrolnitrin Chemical compound [O-][N+](=O)C1=C(Cl)C=CC=C1C1=CNC=C1Cl QJBZDBLBQWFTPZ-UHFFFAOYSA-N 0.000 description 2
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- AFNXATANNDIXLG-SFHVURJKSA-N 1-[(2r)-2-[(4-chlorophenyl)methylsulfanyl]-2-(2,4-dichlorophenyl)ethyl]imidazole Chemical compound C1=CC(Cl)=CC=C1CS[C@H](C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 AFNXATANNDIXLG-SFHVURJKSA-N 0.000 description 1
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- LEZWWPYKPKIXLL-UHFFFAOYSA-N 1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound C1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 LEZWWPYKPKIXLL-UHFFFAOYSA-N 0.000 description 1
- QSWSKDXFOIOXKW-UHFFFAOYSA-N 1h-imidazole;nitric acid Chemical class O[N+]([O-])=O.C1=CNC=N1 QSWSKDXFOIOXKW-UHFFFAOYSA-N 0.000 description 1
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- WHPAGCJNPTUGGD-UHFFFAOYSA-N Croconazole Chemical compound ClC1=CC=CC(COC=2C(=CC=CC=2)C(=C)N2C=NC=C2)=C1 WHPAGCJNPTUGGD-UHFFFAOYSA-N 0.000 description 1
- RHAXSHUQNIEUEY-UHFFFAOYSA-N Epirizole Chemical compound COC1=CC(C)=NN1C1=NC(C)=CC(OC)=N1 RHAXSHUQNIEUEY-UHFFFAOYSA-N 0.000 description 1
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- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- VPHPQNGOVQYUMG-UHFFFAOYSA-N Liranaftate Chemical compound COC1=CC=CC(N(C)C(=S)OC=2C=C3CCCCC3=CC=2)=N1 VPHPQNGOVQYUMG-UHFFFAOYSA-N 0.000 description 1
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 1
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920003082 Povidone K 90 Polymers 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- PPWHTZKZQNXVAE-UHFFFAOYSA-N Tetracaine hydrochloride Chemical compound Cl.CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 PPWHTZKZQNXVAE-UHFFFAOYSA-N 0.000 description 1
- FPVRUILUEYSIMD-RPRRAYFGSA-N [(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(OC(C)=O)[C@@]1(C)C[C@@H]2O FPVRUILUEYSIMD-RPRRAYFGSA-N 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
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- 239000002260 anti-inflammatory agent Substances 0.000 description 1
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- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 description 1
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- PUFQVTATUTYEAL-UHFFFAOYSA-N cinchocaine Chemical compound C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCCN(CC)CC)=C21 PUFQVTATUTYEAL-UHFFFAOYSA-N 0.000 description 1
- IVHBBMHQKZBJEU-UHFFFAOYSA-N cinchocaine hydrochloride Chemical compound [Cl-].C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCC[NH+](CC)CC)=C21 IVHBBMHQKZBJEU-UHFFFAOYSA-N 0.000 description 1
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- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
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- 229960000905 indomethacin Drugs 0.000 description 1
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- 229960003464 mefenamic acid Drugs 0.000 description 1
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- 210000000214 mouth Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
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- JMFOSJNGKJCTMJ-ZHZULCJRSA-N omoconazole Chemical compound C1=CN=CN1C(/C)=C(C=1C(=CC(Cl)=CC=1)Cl)\OCCOC1=CC=C(Cl)C=C1 JMFOSJNGKJCTMJ-ZHZULCJRSA-N 0.000 description 1
- 229960003502 oxybuprocaine Drugs 0.000 description 1
- CMHHMUWAYWTMGS-UHFFFAOYSA-N oxybuprocaine Chemical compound CCCCOC1=CC(C(=O)OCCN(CC)CC)=CC=C1N CMHHMUWAYWTMGS-UHFFFAOYSA-N 0.000 description 1
- HFHZKZSRXITVMK-UHFFFAOYSA-N oxyphenbutazone Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 HFHZKZSRXITVMK-UHFFFAOYSA-N 0.000 description 1
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- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
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- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
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- 150000007519 polyprotic acids Chemical class 0.000 description 1
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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
- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
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- 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
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- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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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
- A61K9/12—Aerosols; Foams
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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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
- A61K9/08—Solutions
Landscapes
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Abstract
本发明是一种配合有碱性药物、聚乙烯吡咯烷酮以及羧乙烯聚合物、且pH为4～9的范围的外用剂。通过本发明，有可能提供一种即使在皮肤的损伤部位也能够达到药物的长效化的新型的外用剂。
Description
技术领域
本发明是关于一种使药物的作用时间延长、并且配合了碱性药物的外用剂。
背景技术
皮肤外用剂是一种可以使药物直接在作用部位发挥作用的优异的剂型，被广泛使用。
作为外用剂的一般性的特点可以举出从皮肤的吸收性低等。为此，以前进行使用透皮吸收促进剂等来促进从皮肤的药物吸收性的研究。可是，对于这些使用了透皮吸收促进剂的外用剂来说，不能得到持续性的药效是其问题之一。
作为使药物滞留在患部，使作用时间延长的方法，在特开平10-265409号中公开有配合脂肪酸多元醇的脂肪酸酯以及某些种类的多元醇的技术。
另一方面，对于注射剂来说，作为使注射给药后的药物持续释放的方法，在WO95/35093号专利中，公开有配合多元酸以及水溶性非离子性聚合物，通过在生理性环境中使其凝胶化而达到使药物持续释放的技术。
可是，在外用剂的长效化技术中，至今已知的这些技术，对于由于伤、炎症等损伤后的皮肤、或者粘膜部位，不能实现充分的长效化是其问题之一。
本发明的目的是提供一种即使是损伤皮肤或者粘膜部位也可以实现药物的长效化的新的技术。
发明的概述
本发明者们为了解决课题进行各种研究的结果，发现在药物为碱性药物时，在制剂中同时配合聚乙烯吡咯烷酮以及羧乙基聚合物，通过调节至特定的pH，即使涂布在损伤皮肤或粘膜部位也可以达到长效化的优秀的外用剂，从而完成了本发明。
即本发明是一种外用剂，其是将碱性药物、聚乙烯吡咯烷酮以及羧乙基聚合物进行配合，且pH为4～9的范围。
在本发明中，所谓碱性药物是指在结构中具有碱性部位的化合物，优选具有氨基的化合物，具体地可以举出抗炎药(丁苯羟酸、吲哚美辛、二氯芬酸、安替匹林、甲灭酸、吡罗昔康、羟基保泰松、保泰松、甲嘧啶唑等)、毛发生长药(长压定等)、血管收缩药(萘甲唑啉、苯肾上腺素等)、抗真菌药(氯康唑、咪康唑、益康唑、克霉唑、异康唑、吡咯尼群、特比奈芬、奥莫康唑、拉诺康唑、利拉萘酯、伊曲康唑、氟康唑、托奈酯、硫康唑、联苯苄唑等)、局部麻醉药(利多卡因、辛可卡因、奥布卡因等)等，也可以使用它们的盐。
碱性药物的配合量根据药物的不同而不同，但通常占制剂总量的0.1～5质量％。
在本发明中使用的所谓羧乙烯聚合物，作为基质成分等可以使用通常在医药品上能够使用的物质。在此，即使使用透明质酸等的基质来替代羧乙烯聚合物，也不能得到充分的长效性，所以在外用剂方面为了实现长效性羧乙烯聚合物是必须的成分。羧乙烯聚合物的配合量与碱性药物1质量份相比优选0.1～6质量份。
在本发明这使用的所谓聚乙烯吡咯烷酮，作为基质成分等可以使用通常在医药品上能够使用的物质，配合量与碱性药物1质量份相比优选0.5～10质量份。
本发明的外用剂，进一步配合聚乙二醇时，因为更加提高向患部的药物长效性，所以优选。配合聚乙二醇时的配合量，优选占制剂总量的10～50质量％。
本发明的外用剂有必要调节pH至4～9的范围，更优选在pH4～8的范围。其原因是因为pH不到4时在维持商品性方面不佳，超过9时有时产生皮肤刺激。
对于pH的调节可以通过在皮肤外用剂上能够配合的中和剂来进行，但特别优选胺类的中和剂。作为在中和剂中优选的物质，可以举出三乙醇胺、二乙醇胺、三乙基胺、二乙基胺、异丙醇胺、二异丙醇胺、三异丙醇胺、二(2-乙基己基)胺、四羟基丙基乙二胺、单乙醇胺等。
在本发明中，进一步配合醇类时，从与皮肤的附着性方面来说优选配合。不配合醇类时，向液性的皮肤涂布时，附着性不好，有时不能充分地实现药效。作为进行配合的醇类，可以使用在外用剂上能够应用的通常的醇类，但作为优选的物质可以举出乙醇、异丙醇、丙二醇、1，3-丁二醇等，也可以将它们混合使用。醇类的配合量优选占制剂总量的10～70质量％。
在本发明中所谓外用剂，是指皮肤外用剂(溶液剂、膏剂、软膏剂、凝胶剂、贴剂、烟雾剂等)，以及也包括经粘膜剂(点鼻剂、口腔用剂、栓剂等)的范畴，可以形成通常的剂型，但在以前缓释化较为困难的外用溶液剂方面，本发明特别地有效。
本发明的外用剂，在不损害本发明的效果的质以及量的范围内，可以配合在外用剂上能够配合的成分，可以用通常的方法制造。
实施发明的最佳形式
以下，通过实施例以及试验例进一步详细地说明本发明。
实施例
显示在表1的配方(W/V％，但是精制水为ml)，以常规方法得到溶液剂。
表1
| 实施例1 | 实施例2 | 比较例1 | 比较例2 | 比较例3 | 比较例4 | |
| 盐酸辛可卡因羧乙烯聚合物聚乙烯吡咯烷酮K90聚丙烯酸透明质酸二异丙醇胺乙醇精制水 | 1.00.21.0--0.2545加至100 | 1.01.01.0--1.2545加至100 | 1.0-----45加至100 | 1.01.0---45加至100 | 1.0--1.0-1.2545加至100 | 1.0---1.0-45加至100 |
| pH(稀释20倍) | 7.33 | 7.70 | 6.35 | 6.33 | 6.50 | 6.25 |
试验例1 皮肤透过性试验
将小形猪(YMP)的冷冻皮肤在室温自然解冻。除去付着在皮下的脂肪，切断成2.5cm平方。用透明粘胶带粘贴剥离20次，使出现损伤。用有效面积0.95cm2的扩散池，接收液使用pH7.4的磷酸缓冲液3ml，保持在37℃进行搅拌。于适当的时间间隔反复进行采取接收液1ml、并补充新鲜溶液的操作。通过HPLC法测定出取出的接收液的药物浓度。
结果见表2。
表2
| 实施例1 | 实施例2 | 比较例1 | 比较例2 | 比较例3 | 比较例4 | |
| ①12-24h②32-48h②/①×100(％) | 22.74326.263115.5 | 32.57727.41884.2 | 60.90032.59553.5 | 77.43126.61934.4 | 84.78430.89136.4 | 66.17525.01037.8 |
实施例3
用盐酸利多卡因2质量％、醋酸地塞米松0.02质量％、聚氧乙烯山梨糖醇酐单硬脂酸酯1质量％、液体石蜡5质量％、硬脂醇1质量％、一缩二丙二醇10质量％、聚乙烯吡咯烷酮K30 1质量％、羧乙烯聚合物0.5质量％、二异丙醇胺1质量％以及精制水加至总量到100g的配方，经常法得到凝胶水浆剂。
实施例4
用盐酸利多卡因1质量％、羧乙烯聚合物0.1质量％、聚乙烯吡咯烷酮1.0质量％、三乙醇胺0.125质量％、聚乙二醇400 10质量％、乙醇50质量％以及精制水加至总量到100ml的配方，得到溶液剂(pH＝6.67)。
实施例5
用硝酸咪唑1.0质量％、聚氧乙烯山梨糖醇酐单硬脂酸酯2.0质量％、中链脂肪酸三甘油酯(パナセ-ト)5.0质量％、硬脂醇1.0质量％、鲸蜡醇1.0质量％、聚乙烯吡咯烷酮K90 1.0质量％、羧乙烯聚合物0.3质量％、二乙醇胺0.35质量％、单硬脂酸山梨糖醇酐酯1.0％以及精制水加至总量到100g的配方，得到凝胶水浆剂。
工业上的应用前景
通过本发明，可以提供一种使碱性药物长效化的新型的技术，在即使对于损伤皮肤也可以实现长效化的一日一次给药型外用剂等方面是有用的。
Claims (8)
1.一种外用剂，其含有碱性药物、聚乙烯吡咯烷酮、羧乙烯聚合物以及一定量的胺类中和剂，其量等于或高于中和羧乙烯聚合物所需的量并且pH为4～9的范围，其中羧乙烯聚合物的配合量，与碱性药物1质量份相比为0.1-6质量份，并且聚乙烯吡咯烷酮的配合量，与碱性药物1质量份相比为0.5-10质量份。
2.权利要求第1项记载的外用剂，其剂型是溶液剂。
3.权利要求第1项记载的外用剂，其特征是还配合有聚乙二醇。
4.权利要求第3项记载的外用剂，聚乙二醇的配合量为制剂总量的10～50质量％。
5.权利要求第1项记载的外用剂，进一步配合有醇。
6.权利要求第5项记载的外用剂，其中醇是从乙醇、异丙醇、异硬脂醇、丙二醇、1，3-丁二醇以及一缩二丙二醇选择的至少1种醇。
7.权利要求第5项记载的外用剂，其中醇的配合量为制剂总量的10～70质量％。
8.权利要求第1项记载的外用剂，其中胺类中和剂选自三乙醇胺、二乙醇胺、三乙基胺、二乙基胺、异丙醇胺、二异丙醇胺、三异丙醇胺、二(2-乙基己基)胺、四羟基丙基乙二胺和单乙醇胺。
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| KR20010099975A (ko) | 2001-11-09 |
| EP1142588A4 (en) | 2007-01-10 |
| CA2356310A1 (en) | 2000-07-06 |
| EP1142588A1 (en) | 2001-10-10 |
| WO2000038731A1 (en) | 2000-07-06 |
| US6627217B1 (en) | 2003-09-30 |
| AU769224B2 (en) | 2004-01-22 |
| HK1042653B (zh) | 2005-09-30 |
| AU1802800A (en) | 2000-07-31 |
| CN1332639A (zh) | 2002-01-23 |
| CA2356310C (en) | 2007-11-06 |
| JP4557113B2 (ja) | 2010-10-06 |
| HK1042653A1 (en) | 2002-08-23 |
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