CN1136919C - 含有米诺地尔的外用组合物 - Google Patents
含有米诺地尔的外用组合物 Download PDFInfo
- Publication number
- CN1136919C CN1136919C CNB998066001A CN99806600A CN1136919C CN 1136919 C CN1136919 C CN 1136919C CN B998066001 A CNB998066001 A CN B998066001A CN 99806600 A CN99806600 A CN 99806600A CN 1136919 C CN1136919 C CN 1136919C
- Authority
- CN
- China
- Prior art keywords
- minoxidil
- antihistaminic
- topical composition
- comparative examples
- hours
- 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.)
- Expired - Fee Related
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- 229960003632 minoxidil Drugs 0.000 title claims abstract description 29
- 239000000203 mixture Substances 0.000 title claims abstract description 20
- 239000000739 antihistaminic agent Substances 0.000 claims abstract description 13
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 claims abstract description 7
- 229960000520 diphenhydramine Drugs 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000000699 topical effect Effects 0.000 claims description 13
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- 239000002085 irritant Substances 0.000 claims description 5
- 231100000021 irritant Toxicity 0.000 claims description 5
- CPHGOBGXZQKCKI-UHFFFAOYSA-N 4,5-diphenyl-1h-imidazole Chemical compound N1C=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 CPHGOBGXZQKCKI-UHFFFAOYSA-N 0.000 abstract description 4
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- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 5
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- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 description 2
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- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- FPXKNYVSOKOLKD-BTJKTKAUSA-N (z)-but-2-enedioic acid;n-chloroaniline Chemical compound OC(=O)\C=C/C(O)=O.ClNC1=CC=CC=C1 FPXKNYVSOKOLKD-BTJKTKAUSA-N 0.000 description 1
- PXGILEVFPBXLEB-UHFFFAOYSA-N 1,2-dimethyl-3-propan-2-ylazulene Chemical compound C1=CC=CC=C2C(C(C)C)=C(C)C(C)=C21 PXGILEVFPBXLEB-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- IJALWSVNUBBQRA-UHFFFAOYSA-N 4-Isopropyl-3-methylphenol Chemical compound CC(C)C1=CC=C(O)C=C1C IJALWSVNUBBQRA-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
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- 240000008574 Capsicum frutescens Species 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 1
- 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 1
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- RZMKWKZIJJNSLQ-UHFFFAOYSA-M carpronium chloride Chemical compound [Cl-].COC(=O)CCC[N+](C)(C)C RZMKWKZIJJNSLQ-UHFFFAOYSA-M 0.000 description 1
- 229950003631 carpronium chloride Drugs 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
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- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 1
- 229940043276 diisopropanolamine Drugs 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
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- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- TXGSOSAONMOPDL-UHFFFAOYSA-N propan-2-yl 3,4,5-trihydroxybenzoate Chemical compound CC(C)OC(=O)C1=CC(O)=C(O)C(O)=C1 TXGSOSAONMOPDL-UHFFFAOYSA-N 0.000 description 1
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- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
- A61K8/411—Aromatic amines, i.e. where the amino group is directly linked to the aromatic nucleus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
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Abstract
本发明提供了一种外用组合物，其中含有米诺地尔和每1重量份米诺地尔0.01至2重量份的至少一种抗组胺药，所述抗组胺药选自马来酸氯苯那敏、双苯味唑、苯海拉明及其盐的药物。
Description
技术领域
本发明涉及含有米诺地尔的外用组合物，当将该组合物涂敷在皮肤上时具有低皮肤刺激性。
背景技术
现已发现高血压治疗药米诺地尔(2，4-二氨基-6-哌啶子基嘧啶-3-氧化物)引起多毛症的副作用，因此目前已在外用组合物中将其作为一种有效成分用于治疗生殖性脱发或皮脂溢脱发。然而，据报导称含有米诺地尔的外用组合物在使用时很少有副作用如皮肤刺激(《接触性皮炎)》(Contact Dermatitis)1987：17：44)。通常，二醇类(例如甘油)和抗炎药(例如甘草次酸)适用于治愈药物诱发的皮肤刺激，但当它们与米诺地尔联合应用时对于皮肤刺激无法产生足够的抑制作用。
发明公开
作为解决上述问题所做的大量研究的结果，本发明人发现，通过将含米诺地尔的外用组合物与用作缓解瘙痒的抗组胺药联合给药可以意外地减轻含米诺地尔的外用组合物的皮肤刺激副作用，由此完成了本发明。也就是说，本发明涉及含有米诺地尔和抗组胺药的外用组合物。
本发明所述的外用组合物适宜含有0.1至5％(重量)的米诺地尔，和0.01至5％(重量)的抗组胺药。当米诺地尔的含量低于0.1％(重量)时，无法达到预期的治疗效果，而当超过5％(重量)时，可能出现降血压作用的危险。此外，当抗组胺药的含量低于0.01％(重量)时，对皮肤刺激的抑制作用较弱，相反地，当超过5％(重量)时，会出现由抗组胺药自身引起的皮肤刺激的可能性。对于米诺地尔和抗组胺药的含量比例，以每1重量份米诺地尔计，所述抗组胺药的量适宜为0.01至2重量份。
本发明抗组胺药的优选实例是马来酸氯苯那敏、双苯咪唑、苯海拉明及其盐。以每1重量份米诺地尔计，所述抗组胺药的用量对于马来酸氯苯那敏(chlorphenylamine maleate)或双苯咪唑来说优选是0.01至1重量份，并且对于苯海拉明或其盐来说优选0.02至2重量份。这些抗组胺药也适合联合应用。
为了进一步减小本发明外用组合物的皮肤刺激性，还优选在该组合物中掺混抗炎药。适用的抗炎剂包括甘草次酸、甘草酸、它们的盐、愈创蓝油烃和薁磺酸钠。对抗炎药的用量没有特别限定，除非本发明的疗效由此而降低，但优选的抗炎药量是0.05至1％(重量)。
本发明的外用组合物可以含有除上述有效成分以外的有效成分。其具体实例包括：卡普氯铵、烟酸苄酯、醋酸生育酚、脲、水杨酸、透明质酸钠、硫酸软骨素、天然药(例如獐牙菜属、人参、辣椒属、plantworm vegetative wags、藏红花或其提取物)、杀微生物药(例如葡萄糖酸洗必太、异丙基甲基苯酚、季铵盐或扁柏酚)。
如果必要，本发明的外用组合物可以含有常用于制备外用制剂的成分，该外用制剂以所需形式如液体、霜剂、软膏、凝胶或气溶胶应用；并且所述成分的具体实例是水、低级醇、增溶剂(例如脂肪酸酯、多元醇、多元醇脂肪酸酯、中链脂肪酸甘油酯、植物油、动物油、烷基甘油醚和烃类)、表面活性剂(例如非离子表面活性剂、卵磷脂衍生物和高分子乳化剂)、乳化稳定剂、胶凝剂、粘合剂、抗氧剂(例如二丁基羟基甲苯和没食子酸异丙酯)、清凉剂(例如醇、薄荷油和樟脑)、香料或染料。
实施本发明的最佳方式
本发明可以提供低皮肤刺激性的含米诺地尔外用组合物。本发明将参考以下实施例和实验例来详细说明。实施例1米诺地尔 1.0(w/v％)马来酸氯苯那敏 0.1丙二醇 10.0变性乙醇 60.0纯水 余量，至100ml
搅拌上述成分且均匀溶解，得到外用液体制剂。
实施例2米诺地尔 1.0(w/v％)盐酸苯海拉明 0.2甘草次酸 0.1醋酸生育酚 0.11-醇 0.3丙二醇 10.0变性乙醇 60.0纯水 余量，至100.0ml
搅拌上述成分且均匀溶解，得到外用液体制剂。
实施例3米诺地尔 5.0(w/w％)双苯咪唑 1.0水杨酸苯海拉明 2.0薁磺酸钠 0.5中链脂肪酸甘油三酯 20.0己二酸二异丙酯 5.0丙二醇 12.0聚氧乙烯脱水山梨糖醇 6.0一硬脂酸酯脱水山梨糖醇一硬脂酸酯 3.0甘油一硬脂酸酯 8.0纯水 余量，至100g
按照常规方法可以由上述成分获得外用霜剂。
实施例4米诺地尔 0.5(w/w％)苯海拉明 0.02甘草酸二钾 0.1二甲基异丙基薁 0.01聚乙二醇一硬脂酸酯 5.0己二酸二异丙酯 3.01，3-丁二醇 8.0聚乙烯吡咯烷酮 0.5羧乙烯基聚合物 1.5二异丙醇胺 适量变性乙醇 30.0纯水 余量，至100g
按照常规方法由上述成分可以获得外用凝胶制剂。
实施例5米诺地尔 0.1(w/w％)马来酸氯苯那敏 0.008聚乙烯脱水山梨糖醇三硬脂酸 1.2酯己二酸二异丙酯 2.01，3-丁二醇 1.2变性乙醇 20.0纯水 15.152异戊烷 10.0液化石油气 3.0二甲醚 47.0
按照常规方法由上述成分可以获得外用气溶胶制剂。实验实施例1
三名被鉴定为因使用含米诺地尔外用制剂引起皮肤刺激的对象分别封闭粘贴上硬膏剂以进行斑片试验(最小尺寸，Torii医药公司)，硬膏剂上涂布有各种10μg的按照表1制备的液体制剂。同时，以相同方式再粘贴上未涂布的硬膏剂作为空白。24小时后，撕下硬膏剂，在撕下硬膏剂后即刻、1小时、3小时、5小时和24时用目测评判刺激分值。目测评判按照下列标准进行评分。
皮肤刺激的目测评判标准：
无反应 0
轻微红斑 1
清晰红斑 2
结果如表2-4所示。
表1
| 实施例1 | 对照实施例1 | 对照实施例2 | 对照实施例3 | |
| 米诺地尔马来酸氯苯那敏甘草次酸丙二醇变性乙醇纯水 | 1.00.1-10.060.0余量，至100ml | 1.0--10.060.0余量，至100ml | 1.0-0.110.060.0余量，至100ml | ---10.060.0余量，至100ml |
表2 对象A的斑片试验结果
| 即刻后 | 1小时后 | 3小时后 | 5小时后 | 24小时后 | |
| 实施例1对照实施例1对照实施例2对照实施例3空白 | 02210 | 02200 | 02200 | 02200 | 02200 |
表3对象B的斑片试验结果
| 即刻后 | 1小时后 | 3小时后 | 5小时后 | 24小时后 | |
| 实施例1对照实施例1对照实施例2对照实施例3空白 | 11110 | 01110 | 02100 | 02200 | 02100 |
表4对象C的斑片试验结果
| 即刻后 | 1小时后 | 3小时后 | 5小时后 | 24小时后 | |
| 实施例1对照实施例1对照实施例2对照实施例3空白 | 01200 | 01100 | 02200 | 02200 | 01100 |
表2至4的结果证明，实施例1获得的液体制剂显著降低了米诺地尔的刺激性，其具有与实施例3的制剂和空白对照大致相同的低评分级别，实施例3的制剂和空白对照都不含有米诺地尔。它们还证实，实施例1的液体制剂对皮肤刺激性的抑制作用比由实施例2获得的制剂高，实施例2的制剂含有广泛用于抑制皮肤刺激的甘草次酸。
工业实用性
本发明提供了降低皮肤刺激性的含米诺地尔的外用组合物。
Claims (1)
1.一种具有降低的皮肤刺激的外用组合物，其中含有米诺地尔和每1重量份米诺地尔0.04至0.2重量份的至少一种抗组胺药，所述抗组胺药选自马来酸氯苯那敏、苯海拉明及其盐。
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| Application Number | Priority Date | Filing Date | Title |
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| JP144598/1998 | 1998-05-26 | ||
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| CN1303302A CN1303302A (zh) | 2001-07-11 |
| CN1136919C true CN1136919C (zh) | 2004-02-04 |
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| EP (1) | EP1080730A1 (zh) |
| KR (1) | KR20010071319A (zh) |
| CN (1) | CN1136919C (zh) |
| AU (1) | AU744491B2 (zh) |
| CA (1) | CA2332881A1 (zh) |
| HK (1) | HK1036761A1 (zh) |
| ID (1) | ID26723A (zh) |
| NZ (1) | NZ508397A (zh) |
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| US6342496B1 (en) * | 1999-03-01 | 2002-01-29 | Sepracor Inc. | Bupropion metabolites and methods of use |
| HUP0300417A2 (hu) * | 2000-04-07 | 2003-08-28 | Taisho Pharmaceutical Co., Ltd. | Hajnövesztő kompozíciók és eljárás azok stabilizálására a kristálykiválás gátlásával |
| FR2883170A1 (fr) * | 2005-03-15 | 2006-09-22 | Oreal | Utilisation d'agents tels que des donneurs ou liberateurs non polymeriques de monoxyde d'azote pour colorer naturellement la peau |
| FR2883177B1 (fr) * | 2005-03-15 | 2008-01-25 | Oreal | Utilisation d'agrnets tels que des donneurs ou liberateurs non polymeriques de monoxyde d'azote pour repulper et/ou colorer naturellement les levres |
| WO2006097348A1 (en) * | 2005-03-15 | 2006-09-21 | L'oreal | Use of agents such as nonpolymeric nitric oxide donors for making the lips full again and/or colouring the lips |
| FR2883171B1 (fr) * | 2005-03-15 | 2007-05-11 | Oreal | Utilisation d'agents tels que des donneurs ou liberateurs non polymeriques de monoxyde d'azote pour diminuer les poches et/ou les cernes perioculaires |
| US9750812B2 (en) | 2008-09-27 | 2017-09-05 | Jina Pharmaceuticals, Inc. | Lipid based pharmaceutical preparations for oral and topical application; their compositions, methods, and uses thereof |
| CN104955460B (zh) * | 2013-01-31 | 2018-06-19 | 富士胶片株式会社 | 乳化组合物 |
| JP2017078044A (ja) * | 2015-10-21 | 2017-04-27 | 大正製薬株式会社 | 発毛剤組成物 |
| JP2021134178A (ja) * | 2020-02-27 | 2021-09-13 | アンファー株式会社 | グリセリン配合によるミノキシジル含有育毛剤の連用塗布に伴う炎症及び刺激の低減方法並びに炎症抑制のための育毛外用剤 |
| CN116120280A (zh) * | 2021-11-12 | 2023-05-16 | 成都贝诺科成生物科技有限公司 | 一种电荷平衡的复合物、其制备方法及其用途 |
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| GB8630721D0 (en) | 1986-12-23 | 1987-02-04 | Unilever Plc | Cosmetic compositions |
| US4888354A (en) * | 1987-12-21 | 1989-12-19 | Theratech, Inc. | Skin penetration enhancement using free base and acid addition salt combinations of active agents |
| BE1003001A6 (fr) | 1989-03-21 | 1991-10-22 | Coppe Jan | Composition a mettre en oeuvre pour le traitement de la calvitie, et procedes faisant usage de celle-ci. |
| JPH0753338A (ja) * | 1993-08-10 | 1995-02-28 | Taisho Pharmaceut Co Ltd | 育毛剤 |
| JPH10167934A (ja) * | 1996-12-05 | 1998-06-23 | Taisho Pharmaceut Co Ltd | 育毛剤 |
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1999
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- 1999-05-25 CN CNB998066001A patent/CN1136919C/zh not_active Expired - Fee Related
- 1999-05-25 KR KR1020007013274A patent/KR20010071319A/ko not_active Application Discontinuation
- 1999-05-25 EP EP99921248A patent/EP1080730A1/en not_active Withdrawn
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| Publication number | Publication date |
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| AU3851399A (en) | 1999-12-13 |
| KR20010071319A (ko) | 2001-07-28 |
| WO1999061059A8 (fr) | 2000-01-27 |
| EP1080730A1 (en) | 2001-03-07 |
| AU744491B2 (en) | 2002-02-28 |
| CN1303302A (zh) | 2001-07-11 |
| HK1036761A1 (en) | 2002-01-18 |
| NZ508397A (en) | 2002-05-31 |
| CA2332881A1 (en) | 1999-12-02 |
| ID26723A (id) | 2001-02-01 |
| WO1999061059A1 (fr) | 1999-12-02 |
| US6265412B1 (en) | 2001-07-24 |
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