JP2019142972A - タペンタドールの非経口的投与 - Google Patents
タペンタドールの非経口的投与 Download PDFInfo
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- JP2019142972A JP2019142972A JP2019091047A JP2019091047A JP2019142972A JP 2019142972 A JP2019142972 A JP 2019142972A JP 2019091047 A JP2019091047 A JP 2019091047A JP 2019091047 A JP2019091047 A JP 2019091047A JP 2019142972 A JP2019142972 A JP 2019142972A
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- Prior art keywords
- composition
- tapentadol
- administration
- pain
- weight
- Prior art date
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Images
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- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4011369A1 (en) * | 2020-12-14 | 2022-06-15 | G.L. Pharma GmbH | Aqueous pharmaceutical composition comprising tapentadol tartrate |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60156602A (ja) * | 1983-12-23 | 1985-08-16 | スターリング・ドラツグ・インコーポレーテツド | 防腐剤または消毒剤として使用するための組成物 |
| JP2004516265A (ja) * | 2000-12-20 | 2004-06-03 | アンファスター・ファーマスーティカルズ・インコーポレイション | 強化された微生物阻害を有するプロポフォール製剤 |
| JP2008266168A (ja) * | 2007-04-18 | 2008-11-06 | Teika Seiyaku Kk | 眼科用剤 |
| JP2008539269A (ja) * | 2005-04-28 | 2008-11-13 | セラクエスト バイオサイエンシズ エルエルシー | 疼痛を治療するための方法および組成物 |
| JP2010520907A (ja) * | 2007-03-12 | 2010-06-17 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | ニューロパシー痛の治療のための１−フェニル−３−ジメチルアミノ−プロパン化合物の使用 |
| WO2010122442A1 (en) * | 2009-04-21 | 2010-10-28 | Pierre Fabre Dermo-Cosmetique | Paediatric solutions comprising a beta-blocker |
| JP2010536712A (ja) * | 2006-09-06 | 2010-12-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 微生物を死滅させるとともに呼吸器感染症を治療する抗コリン作用薬を含む医薬組成物の使用 |
-
2019
- 2019-05-14 JP JP2019091047A patent/JP2019142972A/ja active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60156602A (ja) * | 1983-12-23 | 1985-08-16 | スターリング・ドラツグ・インコーポレーテツド | 防腐剤または消毒剤として使用するための組成物 |
| JP2004516265A (ja) * | 2000-12-20 | 2004-06-03 | アンファスター・ファーマスーティカルズ・インコーポレイション | 強化された微生物阻害を有するプロポフォール製剤 |
| JP2008539269A (ja) * | 2005-04-28 | 2008-11-13 | セラクエスト バイオサイエンシズ エルエルシー | 疼痛を治療するための方法および組成物 |
| JP2010536712A (ja) * | 2006-09-06 | 2010-12-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 微生物を死滅させるとともに呼吸器感染症を治療する抗コリン作用薬を含む医薬組成物の使用 |
| JP2010520907A (ja) * | 2007-03-12 | 2010-06-17 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | ニューロパシー痛の治療のための１−フェニル−３−ジメチルアミノ−プロパン化合物の使用 |
| JP2008266168A (ja) * | 2007-04-18 | 2008-11-06 | Teika Seiyaku Kk | 眼科用剤 |
| WO2010122442A1 (en) * | 2009-04-21 | 2010-10-28 | Pierre Fabre Dermo-Cosmetique | Paediatric solutions comprising a beta-blocker |
Non-Patent Citations (1)
| Title |
|---|
| J PHARMACOL EXP THER, 2007.10, VOL.323, NO,1, PAGES.265-276, JPN6016035954, ISSN: 0004439345 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4011369A1 (en) * | 2020-12-14 | 2022-06-15 | G.L. Pharma GmbH | Aqueous pharmaceutical composition comprising tapentadol tartrate |
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