JPWO2016175240A1 - 多汗症治療用外用剤 - Google Patents
多汗症治療用外用剤 Download PDFInfo
- Publication number
- JPWO2016175240A1 JPWO2016175240A1 JP2017515577A JP2017515577A JPWO2016175240A1 JP WO2016175240 A1 JPWO2016175240 A1 JP WO2016175240A1 JP 2017515577 A JP2017515577 A JP 2017515577A JP 2017515577 A JP2017515577 A JP 2017515577A JP WO2016175240 A1 JPWO2016175240 A1 JP WO2016175240A1
- Authority
- JP
- Japan
- Prior art keywords
- external preparation
- agent
- oxybutynin
- lotion
- anticholinergic
- 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.)
- Granted
Links
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000003893 lactate salts Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- GBLRQXKSCRCLBZ-IYQFLEDGSA-N meso-doxacurium Chemical compound COC1=C(OC)C(OC)=CC(C[C@@H]2[N@@+](CCC3=C2C(=C(OC)C(OC)=C3)OC)(C)CCCOC(=O)CCC(=O)OCCC[N@@+]2(C)[C@@H](C3=C(OC)C(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=C(OC)C=2)=C1 GBLRQXKSCRCLBZ-IYQFLEDGSA-N 0.000 description 1
- 229960002540 mivacurium Drugs 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 229910052901 montmorillonite Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- QVYRGXJJSLMXQH-UHFFFAOYSA-N orphenadrine Chemical compound C=1C=CC=C(C)C=1C(OCCN(C)C)C1=CC=CC=C1 QVYRGXJJSLMXQH-UHFFFAOYSA-N 0.000 description 1
- 229960003941 orphenadrine Drugs 0.000 description 1
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- NVOYVOBDTVTBDX-PMEUIYRNSA-N oxitropium Chemical compound CC[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1 NVOYVOBDTVTBDX-PMEUIYRNSA-N 0.000 description 1
- 229960000797 oxitropium Drugs 0.000 description 1
- 229960002740 oxyphenonium Drugs 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 229960005457 pancuronium Drugs 0.000 description 1
- GVEAYVLWDAFXET-XGHATYIMSA-N pancuronium Chemical compound C[N+]1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 GVEAYVLWDAFXET-XGHATYIMSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 210000005037 parasympathetic nerve Anatomy 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 1
- 229960005253 procyclidine Drugs 0.000 description 1
- 229960000697 propantheline Drugs 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- YXRDKMPIGHSVRX-OOJCLDBCSA-N rocuronium Chemical compound N1([C@@H]2[C@@H](O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(CC=C)CCCC2)CCOCC1 YXRDKMPIGHSVRX-OOJCLDBCSA-N 0.000 description 1
- 229960000491 rocuronium Drugs 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 229950009846 scopolamine butylbromide Drugs 0.000 description 1
- 229910021647 smectite Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229940032712 succinylcholine Drugs 0.000 description 1
- 229940120904 succinylcholine chloride Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
- 229940110309 tiotropium Drugs 0.000 description 1
- 229960004045 tolterodine Drugs 0.000 description 1
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 description 1
- 229960001032 trihexyphenidyl Drugs 0.000 description 1
- CHQOEHPMXSHGCL-UHFFFAOYSA-N trimethaphan Chemical compound C12C[S+]3CCCC3C2N(CC=2C=CC=CC=2)C(=O)N1CC1=CC=CC=C1 CHQOEHPMXSHGCL-UHFFFAOYSA-N 0.000 description 1
- 229940035742 trimethaphan Drugs 0.000 description 1
- HLXQFVXURMXRPU-UHFFFAOYSA-L trimethyl-[10-(trimethylazaniumyl)decyl]azanium;dibromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCCCCCCC[N+](C)(C)C HLXQFVXURMXRPU-UHFFFAOYSA-L 0.000 description 1
- PYIHTIJNCRKDBV-UHFFFAOYSA-L trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;dichloride Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCCCCC[N+](C)(C)C PYIHTIJNCRKDBV-UHFFFAOYSA-L 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- JFJZZMVDLULRGK-URLMMPGGSA-O tubocurarine Chemical compound C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CCN3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 JFJZZMVDLULRGK-URLMMPGGSA-O 0.000 description 1
- 229960001844 tubocurarine Drugs 0.000 description 1
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
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- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A—HUMAN NECESSITIES
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Abstract
Description
表1の組成に従ってローション剤を調製し、溶解状態を目視で確認した。さらに、ローション剤をブタの皮膚に塗布し、オキシブチニンの毛嚢への集積量を以下の方法で測定した。
1)軽く毛刈りしたブタの皮膚5cm2にローション剤20μLを塗布した。個体数n=3。
2)6時間後、消毒用エタノールで皮膚表面を清拭し、リン酸緩衝液で流水洗浄し、皮膚表面に付着するオキシブチニンを除去した。
3)皮膚から毛20本分の毛嚢部分を採取した。
4)抽出液1mLを用いて毛嚢からオキシブチニンを抽出した。抽出液として、以下の移動相を用いた。
5)高速液体クロマトグラフによりオキシブチニンの濃度を測定した。高速液体クロマトグラフの条件は以下の通りである。
移動相:0.1w/w%リン酸水溶液(ドデシル硫酸ナトリウムを0.5w/v%含む):アセトニトリル=45:55(v/v)
流速:1.5mL/分
カラム:TSKgel ODS−80Ts(東ソー株式会社)
保持時間:10分
表3の組成に従ってローション剤を調製した。ピロカルピン誘発発汗試験により、ローション剤の発汗抑制作用を測定した。また、試験例1と同様の方法により、ローション剤をブタの皮膚に塗布し、オキシブチニンの濃度を測定した。
1)ローション剤を40質量%エタノール水溶液で12倍に希釈した。
2)マウスの足蹠の約0.5cm2にローション剤10μL又は15μLを塗布した。個体数n=5〜6。
3)4時間後に麻酔下でヨウ素及びデンプン溶液を足蹠に塗布した。
4)ピロカルピン5μg/足を皮内投与した。
5)5分後にヨウ素デンプン反応により生じる黒点の個数を計数した。
表4の組成に従ってローション剤を調製した。ピロカルピン誘発発汗試験により、ローション剤の発汗抑制作用を測定した。
1)ローション剤を40質量%エタノール水溶液で12倍に希釈した。
2)マウスの足蹠の約0.5cm2にローション剤10μLを塗布した。個体数n=6。
3)3時間後に足蹠を洗浄し、マウスを1時間放置した後、麻酔下でヨウ素及びデンプン溶液を足蹠に塗布した。
4)ピロカルピン15μg/足を皮内投与した。
5)5分後にヨウ素デンプン反応により生じる黒点の個数を計数した。
Claims (5)
- 水、抗コリン作用薬並びに乳酸塩、酒石酸塩、酢酸塩及びリン酸塩からなる群から選択される1以上の塩を含む、多汗症治療用外用剤。
- 抗コリン作用薬が、オキシブチニン又はその薬学的に許容される塩である、請求項1に記載の外用剤。
- 塩が、乳酸ナトリウムである、請求項1又は2に記載の外用剤。
- 液剤である、請求項1〜3のいずれか一項に記載の外用剤。
- ローションの剤形である、請求項4に記載の外用剤。
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WO2019236429A1 (en) * | 2018-06-04 | 2019-12-12 | Nm Therapeutics, Llc | Method and apparatus for treatment of hyperhidrosis |
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US10010494B2 (en) | 2005-10-19 | 2018-07-03 | Menni Menashe Zinger | Methods for the treatment of hyperhidrosis |
KR101317924B1 (ko) | 2011-05-17 | 2013-10-16 | 김동진 | 글리코피롤레이트의 합성방법 및 이 활성성분을 함유하는 약학적 조성물의 제조방법 |
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WO2010062930A1 (en) * | 2008-11-26 | 2010-06-03 | Dry Pharma, Llc | Compositions and methods for hyperhidrosis |
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