CN108366983A - L-鸟氨酸苯乙酸盐制剂 - Google Patents
L-鸟氨酸苯乙酸盐制剂 Download PDFInfo
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- CN108366983A CN108366983A CN201680066488.5A CN201680066488A CN108366983A CN 108366983 A CN108366983 A CN 108366983A CN 201680066488 A CN201680066488 A CN 201680066488A CN 108366983 A CN108366983 A CN 108366983A
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- Prior art keywords
- plasma
- oral
- phenylacetylglutamine
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- max
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Landscapes
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111062923.6A CN113768863A (zh) | 2015-11-13 | 2016-11-11 | L-鸟氨酸苯乙酸盐制剂 |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562255300P | 2015-11-13 | 2015-11-13 | |
| US62/255,300 | 2015-11-13 | ||
| US201662276754P | 2016-01-08 | 2016-01-08 | |
| US62/276,754 | 2016-01-08 | ||
| US15/133,087 US20160338982A1 (en) | 2015-04-20 | 2016-04-19 | Formulations of l-ornithine phenylacetate |
| US15/133,087 | 2016-04-19 | ||
| PCT/US2016/061678 WO2017083758A1 (en) | 2015-11-13 | 2016-11-11 | Formulation of l-ornithine phenylacetate |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111062923.6A Division CN113768863A (zh) | 2015-11-13 | 2016-11-11 | L-鸟氨酸苯乙酸盐制剂 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108366983A true CN108366983A (zh) | 2018-08-03 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| CN202111062923.6A Pending CN113768863A (zh) | 2015-11-13 | 2016-11-11 | L-鸟氨酸苯乙酸盐制剂 |
| CN201680066488.5A Pending CN108366983A (zh) | 2015-11-13 | 2016-11-11 | L-鸟氨酸苯乙酸盐制剂 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN202111062923.6A Pending CN113768863A (zh) | 2015-11-13 | 2016-11-11 | L-鸟氨酸苯乙酸盐制剂 |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP3373923A4 (ko) |
| JP (2) | JP7294807B2 (ko) |
| KR (1) | KR20180086431A (ko) |
| CN (2) | CN113768863A (ko) |
| AU (2) | AU2016353350B2 (ko) |
| BR (1) | BR112018009349A8 (ko) |
| CA (1) | CA3004331A1 (ko) |
| IL (1) | IL258630B2 (ko) |
| MX (2) | MX2018005088A (ko) |
| RU (1) | RU2018113801A (ko) |
| SG (1) | SG11201802987UA (ko) |
| WO (1) | WO2017083758A1 (ko) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JOP20190146A1 (ar) | 2016-12-19 | 2019-06-18 | Axcella Health Inc | تركيبات حمض أميني وطرق لمعالجة أمراض الكبد |
| JP7266581B2 (ja) | 2017-08-14 | 2023-04-28 | アクセラ・ヘルス・インコーポレイテッド | 肝疾患の治療のためのアミノ酸組成物 |
| US10596136B2 (en) | 2018-06-20 | 2020-03-24 | Axcella Health Inc. | Compositions and methods for the treatment of fat infiltration in muscle |
| MX2022004449A (es) * | 2019-10-16 | 2022-08-04 | Ocera Therapeutics Inc | Dosis y usos de fenilacetato de ornitina para el tratamiento de hiperamonemia. |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101102816A (zh) * | 2004-11-26 | 2008-01-09 | Ucl商业有限公司 | 用于治疗肝性脑病的含有鸟氨酸和苯基乙酸（phenylacetate)或苯基丁酸（phenylbutyrate)的组合物 |
| CN101626769A (zh) * | 2007-02-22 | 2010-01-13 | 赢创罗姆有限责任公司 | 含有活性物质基质与聚合物包衣的丸剂和制备所述丸剂的方法 |
| CN102625699A (zh) * | 2009-06-08 | 2012-08-01 | Ucl商业有限公司 | 使用l-鸟氨酸苯乙酸盐治疗门静脉高压和恢复肝功能 |
| CN103502203A (zh) * | 2010-10-06 | 2014-01-08 | 欧塞拉治疗有限公司 | 制备l-鸟氨酸苯基乙酸盐的方法 |
| CN103705490A (zh) * | 2013-10-31 | 2014-04-09 | 蚌埠丰原医药科技发展有限公司 | 一种门冬氨酸鸟氨酸的缓释制剂及其制备工艺 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4783443A (en) | 1986-03-03 | 1988-11-08 | The University Of Chicago | Amino acyl cephalosporin derivatives |
| EP2319581B1 (en) | 2004-11-26 | 2015-02-25 | UCL Business PLC | Compositions comprising ornithine and phenylacetate or phenylbutyrate for treating hepatic encephalopathy |
| AU2015221466B2 (en) | 2009-04-03 | 2017-02-02 | Ocera Therapeutics, Inc. | L-ornithine phenyl acetate and methods of making thereof |
| WO2010115055A1 (en) * | 2009-04-03 | 2010-10-07 | Ocera Therapeutics, Inc. | L-ornithine phenyl acetate and methods of making thereof |
| AU2014250643B2 (en) | 2009-06-08 | 2016-07-14 | Ocera Therapeutics, Inc. | Treatment of portal hypertension and restoration of liver function using L-ornithine phenylacetate |
| AU2016252382A1 (en) * | 2015-04-20 | 2017-11-02 | Ocera Therapeutics, Inc. | Formulations of L-ornithine phenylacetate |
-
2016
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- 2016-11-11 EP EP16865158.6A patent/EP3373923A4/en not_active Withdrawn
- 2016-11-11 BR BR112018009349A patent/BR112018009349A8/pt not_active Application Discontinuation
- 2016-11-11 RU RU2018113801A patent/RU2018113801A/ru not_active Application Discontinuation
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101102816A (zh) * | 2004-11-26 | 2008-01-09 | Ucl商业有限公司 | 用于治疗肝性脑病的含有鸟氨酸和苯基乙酸（phenylacetate)或苯基丁酸（phenylbutyrate)的组合物 |
| CN101626769A (zh) * | 2007-02-22 | 2010-01-13 | 赢创罗姆有限责任公司 | 含有活性物质基质与聚合物包衣的丸剂和制备所述丸剂的方法 |
| CN102625699A (zh) * | 2009-06-08 | 2012-08-01 | Ucl商业有限公司 | 使用l-鸟氨酸苯乙酸盐治疗门静脉高压和恢复肝功能 |
| CN104434894A (zh) * | 2009-06-08 | 2015-03-25 | Ucl商业有限公司 | 使用l-鸟氨酸苯乙酸盐治疗门静脉高压和恢复肝功能 |
| CN103502203A (zh) * | 2010-10-06 | 2014-01-08 | 欧塞拉治疗有限公司 | 制备l-鸟氨酸苯基乙酸盐的方法 |
| CN103705490A (zh) * | 2013-10-31 | 2014-04-09 | 蚌埠丰原医药科技发展有限公司 | 一种门冬氨酸鸟氨酸的缓释制剂及其制备工艺 |
Non-Patent Citations (1)
| Title |
|---|
| 万宏贵: "一种新型治疗肝性脑病的药物：L-鸟氨酸苯乙酸", 《CHINESE JOURNAL OF NEW DRUGS》 * |
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| AU2016353350B2 (en) | 2021-09-23 |
| CA3004331A1 (en) | 2017-05-18 |
| CN113768863A (zh) | 2021-12-10 |
| BR112018009349A2 (pt) | 2018-11-13 |
| AU2016353350A1 (en) | 2018-05-10 |
| IL258630B1 (en) | 2023-04-01 |
| JP2018533601A (ja) | 2018-11-15 |
| SG11201802987UA (en) | 2018-05-30 |
| MX2022001517A (es) | 2022-11-16 |
| JP7294807B2 (ja) | 2023-06-20 |
| EP3373923A1 (en) | 2018-09-19 |
| EP3373923A4 (en) | 2019-07-03 |
| WO2017083758A1 (en) | 2017-05-18 |
| AU2021290236A1 (en) | 2022-02-10 |
| RU2018113801A (ru) | 2019-12-16 |
| KR20180086431A (ko) | 2018-07-31 |
| BR112018009349A8 (pt) | 2019-02-26 |
| MX2018005088A (es) | 2019-05-16 |
| IL258630A (en) | 2018-06-28 |
| JP2022058446A (ja) | 2022-04-12 |
| IL258630B2 (en) | 2023-08-01 |
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