AU2013209610B2 - Methods and formulations for treating sialic acid deficiencies - Google Patents
Methods and formulations for treating sialic acid deficiencies Download PDFInfo
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- AU2013209610B2 AU2013209610B2 AU2013209610A AU2013209610A AU2013209610B2 AU 2013209610 B2 AU2013209610 B2 AU 2013209610B2 AU 2013209610 A AU2013209610 A AU 2013209610A AU 2013209610 A AU2013209610 A AU 2013209610A AU 2013209610 B2 AU2013209610 B2 AU 2013209610B2
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- Prior art keywords
- sialic acid
- extended release
- release formulation
- neuac
- acceptable salt
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
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- A61K9/2022—Organic macromolecular compounds
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- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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US201261709549P | 2012-10-04 | 2012-10-04 | |
US61/709,549 | 2012-10-04 | ||
PCT/US2013/022167 WO2013109906A2 (en) | 2012-01-18 | 2013-01-18 | Methods and formulations for treating sialic acid deficiencies |
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AU2013209610B2 true AU2013209610B2 (en) | 2017-11-30 |
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AU2013209610A Expired - Fee Related AU2013209610B2 (en) | 2012-01-18 | 2013-01-18 | Methods and formulations for treating sialic acid deficiencies |
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US9241896B2 (en) | 2008-12-19 | 2016-01-26 | Ultragenyx Pharmaceutical Inc. | Methods and formulations for treating sialic acid deficiencies |
CN108606956A (zh) | 2010-07-13 | 2018-10-02 | 奥特吉尼克斯制药公司 | 用于治疗唾液酸缺乏的方法和制剂 |
CN103974965B (zh) | 2011-10-24 | 2019-09-24 | 奥特吉尼克斯制药公司 | 唾液酸类似物 |
AR106025A1 (es) | 2015-09-14 | 2017-12-06 | Ultragenyx Pharmaceutical Inc | Formas cristalinas de ácido siálico o una sal o solvato de este |
EP3486326A1 (en) | 2017-11-21 | 2019-05-22 | Jennewein Biotechnologie GmbH | Method for the purification of n-acetylneuraminic acid from a fermentation broth |
CN117969774B (zh) * | 2024-04-02 | 2024-06-11 | 小仙炖霸州食品有限公司 | 一种自动化燕窝检测与分级系统 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008150477A2 (en) * | 2007-05-31 | 2008-12-11 | Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services National Institutes Of Health | N-acetyl mannosamine as a therapeutic agent |
WO2010131712A1 (ja) * | 2009-05-15 | 2010-11-18 | 財団法人ヒューマンサイエンス振興財団 | Gneタンパク質の機能低下に起因する疾患の治療用医薬剤、食品組成物、食品添加物 |
WO2012009474A1 (en) * | 2010-07-13 | 2012-01-19 | Ultragenyx Pharmaceutical Inc. | Method and formulations for treating sialic acid deficiencies |
WO2013063149A1 (en) * | 2011-10-24 | 2013-05-02 | Ultragenyx Pharmaceutical, Inc. | Sialic acid analogs |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100159001A1 (en) * | 2008-12-19 | 2010-06-24 | Cardinal John R | Extended-Release Pharmaceutical Formulations |
-
2013
- 2013-01-18 JP JP2014553457A patent/JP2015504094A/ja active Pending
- 2013-01-18 KR KR1020147022912A patent/KR20150000872A/ko not_active Withdrawn
- 2013-01-18 EP EP13739040.7A patent/EP2804600A4/en not_active Withdrawn
- 2013-01-18 AU AU2013209610A patent/AU2013209610B2/en not_active Expired - Fee Related
- 2013-01-18 CA CA2862836A patent/CA2862836A1/en not_active Abandoned
- 2013-01-18 BR BR112014017587A patent/BR112014017587A8/pt not_active Application Discontinuation
- 2013-01-18 CN CN201380015020.XA patent/CN104271125A/zh active Pending
- 2013-01-18 WO PCT/US2013/022167 patent/WO2013109906A2/en active Application Filing
-
2014
- 2014-06-18 IL IL233225A patent/IL233225A0/en unknown
-
2017
- 2017-07-21 JP JP2017141883A patent/JP2017186381A/ja active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008150477A2 (en) * | 2007-05-31 | 2008-12-11 | Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services National Institutes Of Health | N-acetyl mannosamine as a therapeutic agent |
WO2010131712A1 (ja) * | 2009-05-15 | 2010-11-18 | 財団法人ヒューマンサイエンス振興財団 | Gneタンパク質の機能低下に起因する疾患の治療用医薬剤、食品組成物、食品添加物 |
WO2012009474A1 (en) * | 2010-07-13 | 2012-01-19 | Ultragenyx Pharmaceutical Inc. | Method and formulations for treating sialic acid deficiencies |
WO2013063149A1 (en) * | 2011-10-24 | 2013-05-02 | Ultragenyx Pharmaceutical, Inc. | Sialic acid analogs |
Non-Patent Citations (3)
Title |
---|
May Christine V Malicdan¿, "Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV-hIBM mouse model", Nature Medicine, (20090517), vol. 15, no. 6 * |
NCT01236898, ClinicalTrials.gov, Available from the Internet, <URL: https://clinicaltrials.gov/ct2/show/NCT01236898>, Published 7 September 2011 according to ClinicalTrials.gov, Last Retrieved 21 June 2017 * |
NCT01359319, ClinicalTrials.gov Archive, Available from the Internet, <URL: https://clinicaltrials.gov/archive/NCT01359319/2012_01_17>, Published 17 January 2012 according to ClinicalTrials.gov Archive, Last Retrieved 21 June 2017 * |
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JP2015504094A (ja) | 2015-02-05 |
CA2862836A1 (en) | 2013-07-25 |
WO2013109906A2 (en) | 2013-07-25 |
IL233225A0 (en) | 2014-08-31 |
AU2013209610A1 (en) | 2014-07-10 |
EP2804600A2 (en) | 2014-11-26 |
EP2804600A4 (en) | 2015-09-02 |
KR20150000872A (ko) | 2015-01-05 |
JP2017186381A (ja) | 2017-10-12 |
BR112014017587A8 (pt) | 2017-07-04 |
BR112014017587A2 (pt) | 2017-06-13 |
CN104271125A (zh) | 2015-01-07 |
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