JP5757864B2 - 水溶性アセトアミノフェン類似体 - Google Patents
水溶性アセトアミノフェン類似体 Download PDFInfo
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- JP5757864B2 JP5757864B2 JP2011510691A JP2011510691A JP5757864B2 JP 5757864 B2 JP5757864 B2 JP 5757864B2 JP 2011510691 A JP2011510691 A JP 2011510691A JP 2011510691 A JP2011510691 A JP 2011510691A JP 5757864 B2 JP5757864 B2 JP 5757864B2
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- JP
- Japan
- Prior art keywords
- acetaminophen
- compound
- pharmaceutically acceptable
- composition
- acceptable salt
- 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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- 238000002360 preparation method Methods 0.000 claims description 14
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 11
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 10
- 239000012535 impurity Substances 0.000 claims description 9
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- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 claims description 8
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- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 5
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- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 claims description 4
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- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 4
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- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 claims description 4
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Landscapes
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| US10172797B2 (en) | 2013-12-17 | 2019-01-08 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| US9492444B2 (en) | 2013-12-17 | 2016-11-15 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| EP3169315B1 (en) | 2014-07-17 | 2020-06-24 | Pharmaceutical Manufacturing Research Services, Inc. | Immediate release abuse deterrent liquid fill dosage form |
| CN117164657A (zh) | 2014-08-12 | 2023-12-05 | 莫纳什大学 | 定向淋巴的前药 |
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| MX393568B (es) | 2014-10-21 | 2025-03-24 | Abbvie Inc | Profarmacos de carbidopa y l-dopa y metodos de uso |
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| EP3347340A4 (en) | 2015-09-08 | 2019-01-23 | Monash University | LYMPHENLEITUNGSPRODRUGS |
| JP2019515908A (ja) * | 2016-04-20 | 2019-06-13 | アッヴィ・インコーポレイテッド | カルビドパ及びｌ−ドパプロドラッグ並びに使用方法 |
| US11883497B2 (en) | 2017-08-29 | 2024-01-30 | Puretech Lyt, Inc. | Lymphatic system-directing lipid prodrugs |
| WO2019046491A1 (en) | 2017-08-29 | 2019-03-07 | Ariya Therapeutics, Inc. | LIPIDIC PRODRUGS DIRECTING TO THE LYMPHATIC SYSTEM |
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| UY38473A (es) | 2018-11-15 | 2020-06-30 | Abbvie Inc | Formulaciones farmacéuticas para una administración subcutánea |
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Family Cites Families (36)
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| JP2005516987A (ja) * | 2002-02-05 | 2005-06-09 | ブリストル−マイヤーズ スクイブ カンパニー | Ｎ−置換された３−ヒドロキシ−４−ピリジノン化合物およびそれを含む医薬 |
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| US20050026879A1 (en) * | 2003-07-31 | 2005-02-03 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a tyrosine kinase inhibitor, delta opioid receptor antagonist, neurokinin receptor antagonist, or VCAM inhibitor for treatment of asthma or chronic obstructive pulmonary disease |
| US20070093457A1 (en) * | 2004-02-11 | 2007-04-26 | Nadir Arber | Compositions for treatment of cancer and inflammation with curcumin and at least one nsaid |
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| JP2010511717A (ja) | 2006-12-05 | 2010-04-15 | ニューロジェシックス， インコーポレイテッド | プロドラッグおよびその作成ならびに使用方法 |
| JP5757864B2 (ja) | 2008-05-20 | 2015-08-05 | ニューロジェシックス， インコーポレイテッド | 水溶性アセトアミノフェン類似体 |
| KR101677126B1 (ko) * | 2008-05-20 | 2016-11-22 | 노이로제스엑스, 인코포레이티드 | 탄산염 프로드러그 및 그것의 사용 방법 |
| BRPI0912820A2 (pt) | 2008-05-20 | 2015-10-13 | Neurogesx Inc | pró-fármacos de relação hepatoprotetora de acetaminofeno |
| US8569466B2 (en) | 2008-09-10 | 2013-10-29 | Nnochiri Ekwuribe | Aromatic carboxylic acid derivatives for treatment and prophylaxis of gastrointestinal diseases including colon cancers |
| JP2012520342A (ja) | 2009-03-16 | 2012-09-06 | ジェンメディカ・セラピューティックス・ソシエダッド・リミターダ | 代謝障害を処置するのに有用な抗炎症剤および抗酸化剤のコンジュゲート |
| AU2012312136B2 (en) | 2011-09-22 | 2017-06-29 | Acorda Therapeutics, Inc. | Acetaminophen conjugates, compositions and methods of use thereof |
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- 2009-05-20 RU RU2010151952/04A patent/RU2010151952A/ru not_active Application Discontinuation
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|---|---|
| US11021498B2 (en) | 2021-06-01 |
| JP2014111658A (ja) | 2014-06-19 |
| US20160264605A1 (en) | 2016-09-15 |
| CN105254662A (zh) | 2016-01-20 |
| JP2017057217A (ja) | 2017-03-23 |
| IL209382A0 (en) | 2011-01-31 |
| EP2291348A4 (en) | 2013-05-15 |
| EP2291348A1 (en) | 2011-03-09 |
| JP2016084359A (ja) | 2016-05-19 |
| WO2009143295A1 (en) | 2009-11-26 |
| US20200002364A1 (en) | 2020-01-02 |
| MX2010012648A (es) | 2010-12-14 |
| CA2724877A1 (en) | 2009-11-26 |
| AU2009249067A1 (en) | 2009-11-26 |
| RU2010151952A (ru) | 2012-06-27 |
| KR20110018897A (ko) | 2011-02-24 |
| US10442826B2 (en) | 2019-10-15 |
| JP2020114876A (ja) | 2020-07-30 |
| US20110212926A1 (en) | 2011-09-01 |
| JP2011520977A (ja) | 2011-07-21 |
| CN102149672A (zh) | 2011-08-10 |
| JP6063072B2 (ja) | 2017-01-18 |
| US9981998B2 (en) | 2018-05-29 |
| US20190092795A1 (en) | 2019-03-28 |
| KR101698028B1 (ko) | 2017-01-26 |
| CA2724877C (en) | 2016-09-13 |
| BRPI0912326A2 (pt) | 2015-10-06 |
| JP2018135392A (ja) | 2018-08-30 |
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