KR102443942B1 - 외상성 뇌 손상에 대한 글리세릴 3-하이드록시부티레이트 - Google Patents
외상성 뇌 손상에 대한 글리세릴 3-하이드록시부티레이트 Download PDFInfo
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- KR102443942B1 KR102443942B1 KR1020197020924A KR20197020924A KR102443942B1 KR 102443942 B1 KR102443942 B1 KR 102443942B1 KR 1020197020924 A KR1020197020924 A KR 1020197020924A KR 20197020924 A KR20197020924 A KR 20197020924A KR 102443942 B1 KR102443942 B1 KR 102443942B1
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- hydroxybutyrate
- glyceryl
- tbi
- ester
- administration
- 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.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15/404,396 | 2017-01-12 | ||
| US15/404,396 US9925164B1 (en) | 2017-01-12 | 2017-01-12 | Glyceryl 3-hydroxybutyrates for traumatic brain injury |
| PCT/US2017/063853 WO2018132189A1 (en) | 2017-01-12 | 2017-11-30 | Glyceryl 3-hydroxybutyrates for traumatic brain injury |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20190104546A KR20190104546A (ko) | 2019-09-10 |
| KR102443942B1 true KR102443942B1 (ko) | 2022-09-15 |
Family
ID=61633011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197020924A Active KR102443942B1 (ko) | 2017-01-12 | 2017-11-30 | 외상성 뇌 손상에 대한 글리세릴 3-하이드록시부티레이트 |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US9925164B1 (enExample) |
| EP (1) | EP3568129A4 (enExample) |
| JP (1) | JP7278593B2 (enExample) |
| KR (1) | KR102443942B1 (enExample) |
| CN (1) | CN110114067A (enExample) |
| BR (1) | BR112019014128A2 (enExample) |
| CA (1) | CA3046355C (enExample) |
| IL (1) | IL267934B2 (enExample) |
| MX (1) | MX391851B (enExample) |
| MY (1) | MY207193A (enExample) |
| WO (1) | WO2018132189A1 (enExample) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11103470B2 (en) | 2017-11-22 | 2021-08-31 | Axcess Global Sciences, Llc | Non-racemic beta-hydroxybutyrate compounds and compositions enriched with the R-enantiomer and methods of use |
| US11241403B2 (en) | 2016-03-11 | 2022-02-08 | Axcess Global Sciences, Llc | Beta-hydroxybutyrate mixed salt compositions and methods of use |
| US11944598B2 (en) | 2017-12-19 | 2024-04-02 | Axcess Global Sciences, Llc | Compositions containing s-beta-hydroxybutyrate or non-racemic mixtures enriched with the s-enatiomer |
| US11026929B2 (en) | 2016-04-19 | 2021-06-08 | Keto Patent Group, Inc. | Administration of berberine metabolites |
| US11202769B2 (en) | 2017-11-22 | 2021-12-21 | Axcess Global Sciences, Llc | Ketone body esters of s-beta-hydroxybutyrate and/or s-1,3-butanediol for modifying metabolic function |
| US11806324B2 (en) | 2018-04-18 | 2023-11-07 | Axcess Global Sciences, Llc | Beta-hydroxybutyric acid compositions and methods for oral delivery of ketone bodies |
| US12109182B2 (en) | 2016-04-19 | 2024-10-08 | Axcess Global Sciences, Llc | Administration of R-beta-hydroxybutyrate and related compounds in humans |
| US10925843B2 (en) | 2018-04-18 | 2021-02-23 | Axcess Global Sciences, Llc | Compositions and methods for keto stacking with beta-hydroxybutyrate and acetoacetate |
| US12329734B2 (en) | 2017-12-19 | 2025-06-17 | Axcess Global Sciences, Llc | Use of S-beta-hydroxybutyrate compounds for induction and maintenance of flow |
| US12496283B2 (en) | 2016-04-19 | 2025-12-16 | Axcess Global Sciences, Llc | Administration of R-beta-hydroxybutyrate and related compounds in humans |
| CA3021784A1 (en) * | 2016-04-19 | 2017-10-26 | Keto Patent Group, Inc. | Administration of butyrate, beta-hydroxybutyrate, and related compounds in humans |
| US10376528B2 (en) | 2017-03-10 | 2019-08-13 | Tecton Group, Llc | Composition comprising ketone body and nicotinamide adenine dinucleotide modulator and methyl donor |
| US12171735B2 (en) | 2017-04-19 | 2024-12-24 | Axcess Global Sciences, Llc | Administration of butyrate, beta-hydroxybutyrate, cannabidiol, and related compounds in humans |
| GB201715654D0 (en) | 2017-09-27 | 2017-11-08 | Tdeltas Ltd | Method of treatment |
| US12090129B2 (en) | 2017-11-22 | 2024-09-17 | Axcess Global Sciences, Llc | Non-racemic beta-hydroxybutyrate compounds and compositions enriched with the R-enantiomer and methods of use |
| CN113329990B (zh) * | 2019-01-17 | 2024-06-07 | 凯托利皮克斯治疗有限责任公司 | 羟基羧酸甘油酯的生产方法 |
| US12091383B2 (en) * | 2019-01-17 | 2024-09-17 | Ketolipix Therapeutics Gmbh | Method for producing lipids comprising structural units based on glycerides of hydroxycarboxylc acids |
| US12472200B2 (en) | 2019-05-15 | 2025-11-18 | Axcess Global Sciences, Llc | Autobiotic compositions and method for promoting healthy gut microbiome |
| MY199307A (en) * | 2019-05-30 | 2023-10-24 | Neuroenergy Ventures Inc | Glyceryl tris (beta-hydroxybutyrate) and neuronal transient ischemic attacks |
| EP3956286B1 (de) * | 2019-06-12 | 2023-12-13 | KetoLipix Therapeutics GmbH | Verfahren zur herstellung von polyolbasierten estern, insbesondere polyglycerinestern, von hydroxycarbonsäuren |
| CN113966323B (zh) * | 2019-06-12 | 2023-11-28 | 凯托利皮克斯治疗有限责任公司 | 一种用于生产酮羧酸多元醇基酯的方法 |
| US11969430B1 (en) | 2023-03-10 | 2024-04-30 | Axcess Global Sciences, Llc | Compositions containing paraxanthine and beta-hydroxybutyrate or precursor for increasing neurological and physiological performance |
| US11950616B2 (en) | 2019-06-21 | 2024-04-09 | Axcess Global Sciences, Llc | Non-vasoconstricting energy-promoting compositions containing ketone bodies |
| US12167993B2 (en) | 2019-06-21 | 2024-12-17 | Axcess Global Sciences, Llc | Non-vasoconstricting energy-promoting compositions containing ketone bodies |
| ES2980782T3 (es) * | 2020-07-13 | 2024-10-03 | Ketolipix Therapeutics Gmbh | Procedimiento para la preparación de ésteres de poliglicerol de ácidos policarboxílicos esterificados con oxobutanol |
| US12186297B2 (en) | 2020-08-26 | 2025-01-07 | Axcess Global Sciences, Llc | Compositions and methods for increasing lean-to-fat mass ratio |
| US20240342121A1 (en) * | 2021-07-09 | 2024-10-17 | Georgia State University Research Foundation, Inc. | The use of beta-hydroxybutyrates for the treatment or prevention of aneurysms and dissections |
| JP2024541228A (ja) | 2021-11-12 | 2024-11-08 | アークサーダ・アクチェンゲゼルシャフト | ポリオール由来の化合物 |
| EP4412987A1 (en) | 2021-11-26 | 2024-08-14 | Arxada AG | Acetoacetate based ketals |
| US12023382B2 (en) | 2022-01-18 | 2024-07-02 | Today Inc. | Molecules, formulations, and methods for nutritional support of athletes, patients, and others |
| WO2023139357A1 (en) * | 2022-01-18 | 2023-07-27 | Today Inc. | Molecules, nutritional formulations, and methods of providing nutritional support |
| EP4631364A2 (en) * | 2022-03-04 | 2025-10-15 | 2508 Biosciences LLC | Compositions and methods to promote brain health |
| EP4605371A1 (en) | 2022-10-18 | 2025-08-27 | Arxada AG | Polyol-derived compounds |
| WO2025074001A2 (en) | 2023-10-05 | 2025-04-10 | Arxada Ag | Enzymatic reduction of acetoacetate |
| WO2025196156A1 (en) | 2024-03-20 | 2025-09-25 | Arxada Ag | Continuous hydrogenation process of acetoacetate esters |
| WO2025224319A1 (en) | 2024-04-25 | 2025-10-30 | Arxada Ag | Reduction of acetoacetate esters in the presence of amines |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008005818A1 (en) * | 2006-06-30 | 2008-01-10 | Stepan Co | Glyceride esters for the treatment of diseases associated with reduced neuronal metabolism of glucose |
| WO2011101171A1 (en) | 2010-02-22 | 2011-08-25 | Tdeltas Limited | Nutritional composition |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4598203B2 (ja) * | 1995-12-01 | 2010-12-15 | ビーティージー・インターナショナル・リミテッド | 脳機能改善剤 |
| US6323237B1 (en) | 1997-03-17 | 2001-11-27 | Btg International Limited | Therapeutic compositions |
| AU749638B2 (en) | 1997-03-17 | 2002-06-27 | Btg International Limited | Therapeutic compositions |
| GB0420856D0 (en) * | 2004-09-20 | 2004-10-20 | Ketocytonyx Inc | Cns modulators |
| EP1885398B1 (en) * | 2005-05-26 | 2015-07-08 | The Regents of the University of Colorado, a body corporate | Inhibition of the alternative complement pathway for treatment of traumatic brain injury, spinal cord injury and related conditions |
| PT2001293T (pt) | 2006-04-03 | 2018-11-28 | Accera Inc | Utilização de compostos cetogénicos para tratamento de comprometimento da memória associado à idade |
| MX2009011002A (es) | 2007-04-12 | 2010-03-15 | Univ Minnesota | Composiciones de proteccion de isquemia/reperfusion y metodos de uso. |
| JP2009173766A (ja) | 2008-01-24 | 2009-08-06 | Ono Kogei Kk | 炭素繊維含有コーティング組成物およびその調製方法 |
| US8642654B2 (en) | 2009-04-16 | 2014-02-04 | Isis Innovation Limited | Hydroxybutyrate ester and medical use thereof |
| AU2010207597A1 (en) | 2009-01-24 | 2011-08-18 | Phytopharm Plc | Treatment of neurotrophic factor mediated disorders |
| CA2873057C (en) | 2011-05-09 | 2020-02-25 | University Of South Florida | The use of ketone esters for prevention of cns oxygen toxicity |
| US20140072654A1 (en) | 2011-12-23 | 2014-03-13 | Savind, Inc. | Cancer with metabolic therapy and hyperbaric oxygen |
| FR2997302B1 (fr) | 2012-10-29 | 2015-02-06 | Assist Publ Hopitaux De Paris | Prevention et traitement des deficits en pyruvate deshydrogenase |
| EP3659595A1 (en) | 2012-11-05 | 2020-06-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Ketone bodies to protect tissues from damage by ionizing radiation |
| WO2014085652A1 (en) | 2012-11-28 | 2014-06-05 | University Of South Florida | Targeting cancer with metabolic therapy and hyperbaric oxygen |
| MY180761A (en) | 2013-03-19 | 2020-12-08 | Univ South Florida | Compositions and methods for producing elevated and sustained ketosis |
| WO2015034812A2 (en) * | 2013-09-04 | 2015-03-12 | Beth Israel Deaconess Medical Center | A new ketogenic diet and its use in treating the critically ill |
| EP3094321B1 (en) | 2014-01-13 | 2019-05-01 | University Of South Florida | Methods of sustaining dietary ketosis and its effects on lipid profile |
| US20160078782A1 (en) | 2014-09-17 | 2016-03-17 | The Trustees Of Boston College | Glucose Ketone Index for MetabolicTherapy |
| US9364456B1 (en) | 2015-06-30 | 2016-06-14 | University Of South Florida | Ketone esters for treatment of angelman syndrome |
| US20180200220A1 (en) | 2015-07-10 | 2018-07-19 | Cognate Nutritionals, Inc. | Prophylaxis and mitigation of migraine headaches using ketogenic medium chain triglycerides, ketone esters, and other ketogenic sources |
| US10292952B2 (en) | 2016-03-11 | 2019-05-21 | Axcess Global Sciences, Llc | Mixed salt compositions for maintaining or restoring electrolyte balance while producing elevated and sustained ketosis |
| WO2017165445A1 (en) | 2016-03-21 | 2017-09-28 | Csilla Ari D'agostino | Administration of exogenous ketone to lower blood glucose |
| US10376482B2 (en) | 2016-04-03 | 2019-08-13 | Franco Cavaleri | Butyrate and beta-hydroxybutyrate compositions |
| CA3021784A1 (en) | 2016-04-19 | 2017-10-26 | Keto Patent Group, Inc. | Administration of butyrate, beta-hydroxybutyrate, and related compounds in humans |
| WO2018009208A1 (en) | 2016-07-08 | 2018-01-11 | Cognate Nutritionals, Inc. | Nutritional mitiggation of the cns effects of traumatic brain injury |
| US10588877B2 (en) | 2016-07-21 | 2020-03-17 | Savind, Inc. | Compositions comprising β-hydroxybutyric acid and salt, and methods of using the same |
| US20180057846A1 (en) | 2016-08-30 | 2018-03-01 | KetoneAid Inc. | Partially buffered free acid and/or ketone blend for rapid onset ketosis and metabolic therapy |
| US20180055797A1 (en) | 2016-08-31 | 2018-03-01 | KetoneAid Inc. | Non-racemic ketone salts for rapid-onset nutritional ketosis and metabolic therapy |
| US20210290581A1 (en) | 2016-09-12 | 2021-09-23 | University Of South Florida | Neuroregeneration improved by ketone |
-
2017
- 2017-01-12 US US15/404,396 patent/US9925164B1/en active Active
- 2017-11-30 BR BR112019014128-6A patent/BR112019014128A2/pt not_active Application Discontinuation
- 2017-11-30 EP EP17891194.7A patent/EP3568129A4/en active Pending
- 2017-11-30 IL IL267934A patent/IL267934B2/en unknown
- 2017-11-30 MY MYPI2019003665A patent/MY207193A/en unknown
- 2017-11-30 WO PCT/US2017/063853 patent/WO2018132189A1/en not_active Ceased
- 2017-11-30 CA CA3046355A patent/CA3046355C/en active Active
- 2017-11-30 JP JP2019536598A patent/JP7278593B2/ja active Active
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- 2017-11-30 MX MX2019008269A patent/MX391851B/es unknown
-
2018
- 2018-03-01 US US15/909,240 patent/US10736867B2/en active Active
-
2020
- 2020-06-10 US US16/897,349 patent/US11638702B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008005818A1 (en) * | 2006-06-30 | 2008-01-10 | Stepan Co | Glyceride esters for the treatment of diseases associated with reduced neuronal metabolism of glucose |
| WO2011101171A1 (en) | 2010-02-22 | 2011-08-25 | Tdeltas Limited | Nutritional composition |
Non-Patent Citations (2)
| Title |
|---|
| Critical Care, 15(219), 1-10, 2011.* |
| Journal of Lipid Research, 55(12), 2450-2457, 2014. |
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