JP7278593B2 - 外傷性脳損傷のためのグリセリル3-ヒドロキシブチラート - Google Patents
外傷性脳損傷のためのグリセリル3-ヒドロキシブチラート Download PDFInfo
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- JP7278593B2 JP7278593B2 JP2019536598A JP2019536598A JP7278593B2 JP 7278593 B2 JP7278593 B2 JP 7278593B2 JP 2019536598 A JP2019536598 A JP 2019536598A JP 2019536598 A JP2019536598 A JP 2019536598A JP 7278593 B2 JP7278593 B2 JP 7278593B2
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- hydroxybutyrate
- glyceryl
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- ester
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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)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (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 (3)
| Publication Number | Publication Date |
|---|---|
| JP2020504134A JP2020504134A (ja) | 2020-02-06 |
| JP2020504134A5 JP2020504134A5 (enExample) | 2021-01-14 |
| JP7278593B2 true JP7278593B2 (ja) | 2023-05-22 |
Family
ID=61633011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019536598A Active JP7278593B2 (ja) | 2017-01-12 | 2017-11-30 | 外傷性脳損傷のためのグリセリル3-ヒドロキシブチラート |
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 (35)
| 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 |
| 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 |
| US11026929B2 (en) | 2016-04-19 | 2021-06-08 | Keto Patent Group, Inc. | Administration of berberine metabolites |
| CA3021784A1 (en) * | 2016-04-19 | 2017-10-26 | Keto Patent Group, Inc. | Administration of butyrate, beta-hydroxybutyrate, and related compounds in humans |
| 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 |
| 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 |
| 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 |
| US12329734B2 (en) | 2017-12-19 | 2025-06-17 | Axcess Global Sciences, Llc | Use of S-beta-hydroxybutyrate compounds for induction and maintenance of flow |
| US12091383B2 (en) * | 2019-01-17 | 2024-09-17 | Ketolipix Therapeutics Gmbh | Method for producing lipids comprising structural units based on glycerides of hydroxycarboxylc acids |
| JP7235873B2 (ja) * | 2019-01-17 | 2023-03-08 | アイオーアイ オレオ ゲーエムベーハー | ヒドロキシカルボン酸のグリセリドの製造方法 |
| US12472200B2 (en) | 2019-05-15 | 2025-11-18 | Axcess Global Sciences, Llc | Autobiotic compositions and method for promoting healthy gut microbiome |
| IL288343B2 (en) * | 2019-05-30 | 2024-04-01 | Neuroenergy Ventures Inc | Glyceryl tris (beta-hydroxybutyrate) and neuronal transient ischemic attacks |
| WO2020249195A1 (de) * | 2019-06-12 | 2020-12-17 | Ioi Oleo Gmbh | Verfahren zur herstellung von polyolbasierten estern von ketocarbonsäuren |
| CN114008015B (zh) * | 2019-06-12 | 2024-02-20 | 凯托利皮克斯治疗有限责任公司 | 羟基羧酸多元醇酯、特别是聚甘油酯的制备方法 |
| 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 |
| JP2023543110A (ja) * | 2020-07-13 | 2023-10-13 | ケトリピックス セラポーティクス ゲーエムベーハー | オキソブタノールでエステル化されたポリグリセロールエステルを製造する方法 |
| 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 |
| IL312317B2 (en) | 2021-11-12 | 2025-04-01 | Arxada Ag | Polyol-derived compounds |
| US20250002446A1 (en) | 2021-11-26 | 2025-01-02 | Arxada Ag | Acetoacetate Based Ketals |
| WO2023139357A1 (en) * | 2022-01-18 | 2023-07-27 | Today Inc. | Molecules, nutritional formulations, and methods of providing nutritional support |
| US12023382B2 (en) | 2022-01-18 | 2024-07-02 | Today Inc. | Molecules, formulations, and methods for nutritional support of athletes, patients, and others |
| WO2023167989A2 (en) * | 2022-03-04 | 2023-09-07 | Guardian 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 |
Family Cites Families (32)
| 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 |
| JP4740426B2 (ja) * | 1997-03-17 | 2011-08-03 | ビーティージー・インターナショナル・リミテッド | 治療用組成物 |
| GB0420856D0 (en) * | 2004-09-20 | 2004-10-20 | Ketocytonyx Inc | Cns modulators |
| ES2548700T3 (es) | 2005-05-26 | 2015-10-20 | The Regents Of The University Of Colorado, A Body Corporate | Inhibición de la vía alternativa del complemento para el tratamiento de lesión cerebral traumática, lesión de médula espinal y afecciones relacionadas |
| KR20090003148A (ko) | 2006-04-03 | 2009-01-09 | 액세라인크 | 나이와 관련된 기억 손상의 치료를 위한 케톤 생성조성물의 용도 |
| WO2008005818A1 (en) * | 2006-06-30 | 2008-01-10 | Stepan Co | Glyceride esters for the treatment of diseases associated with reduced neuronal metabolism of glucose |
| CA2684213A1 (en) | 2007-04-12 | 2008-10-23 | Regents Of The University Of Minnesota | Ischemia/reperfusion protection compositions and methods of using |
| 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 |
| EA201190115A1 (ru) | 2009-01-24 | 2012-02-28 | ФИТОФАРМ ПиЭлСи | Лечение расстройств, опосредованных нейротрофическим фактором |
| GB201002983D0 (en) * | 2010-02-22 | 2010-04-07 | Tdeltas Ltd | Nutritinal composition |
| 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 |
| DK2914251T3 (da) | 2012-11-05 | 2019-11-04 | Us Health | Ketonlegemer til beskyttelse af væv mod beskadigelse som følge af ioniseringsstråling |
| EP2925308B1 (en) | 2012-11-28 | 2019-12-25 | University Of South Florida | Targeting cancer with metabolic therapy and hyperbaric oxygen |
| PE20151949A1 (es) | 2013-03-19 | 2016-01-05 | Univ South Florida | Composiciones y metodos para producir cetosis elevada y sostenida |
| 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 |
| CA2973342A1 (en) | 2014-01-13 | 2015-10-15 | 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 |
| WO2017011294A1 (en) | 2015-07-10 | 2017-01-19 | Cognate Nutritionals, Inc. | Prophylaxis and mitigation of migraine headaches using 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 |
| CA3036688A1 (en) | 2016-09-12 | 2018-03-15 | University Of South Florida | Neuroregeneration improved by ketone |
-
2017
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-
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Non-Patent Citations (1)
| Title |
|---|
| IUBMB Life,2012年,Vol.64, No.2,pp.203-207 |
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