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1. 发明申请

US20140308719A1 PROCESS FOR PRODUCING (R)-3-HYDROXYBUTYL (R)-3-HYDROXYBUTYRATE 审中-公开
标题翻译：制备（R）-3-羟基丁基-3-羟基丁酸酯的方法
公开(公告)号：US20140308719A1
公开(公告)日：2014-10-16
申请号：US14213713
申请日：2014-03-14
申请人： GOVERNMENT OF THE USA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , ISIS INNOVATION LTD
发明人： Kieran Clarke , Richard Lewis Veech , M. Todd King
IPC分类号： C12P7/62 , C07C67/02
CPC分类号： C12P7/62 , C07B2200/07 , C07C29/147 , C07C67/03 , C07C69/675 , C07C31/207
摘要： Embodiments of the present invention are directed to processes for the production of (R)-3-hydroxybutyl (R)-3-hydroxybyrate. Poly (R)-3-hydroxybyrate is transesterified with an alcohol, to form a first ester portion and a second ester portion. The first ester portion is reduced to the diol to form a diol portion and the diol portion is reacted with the second ester portion to produce (R)-3-hydroxybutyl (R)-3-hydroxybyrate.
摘要翻译：本发明的实施方案涉及制备（R）-3-羟基丁基（R）-3-羟基丁酸酯的方法。聚（R）-3-羟基丁酸酯用醇酯交换，形成第一酯部分和第二酯部分。将第一酯部分还原成二醇以形成二醇部分，并且将二醇部分与第二酯部分反应以制备（R）-3-羟基丁基（R）-3-羟基丁酸酯。

2. 发明授权

US11566268B2 Process for producing (R)-3-hydroxybutyl (R)-3-hydroxybutyrate 有权
公开(公告)号：US11566268B2
公开(公告)日：2023-01-31
申请号：US14213713
申请日：2014-03-14
申请人： ISIS INNOVATION LTD , GOVERNMENT OF THE USA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
发明人： Kieran Clarke , Richard Lewis Veech , M. Todd King
IPC分类号： C12P7/62 , C07C67/03 , C07C29/147
摘要： Embodiments of the present invention are directed to processes for the production of (R)-3-hydroxybutyl (R)-3-hydroxybyrate. Poly (R)-3-hydroxybyrate is transesterified with an alcohol, to form a first ester portion and a second ester portion. The first ester portion is reduced to the diol to form a diol portion and the diol portion is reacted with the second ester portion to produce (R)-3-hydroxybutyl (R)-3-hydroxybyrate.

3. 发明申请

US20160193173A1 KETONE BODIES AND KETONE BODY ESTERS AS BLOOD LIPID LOWERING AGENTS 审中-公开
标题翻译：酮体和酮体系作为血液淋洗剂
公开(公告)号：US20160193173A1
公开(公告)日：2016-07-07
申请号：US14931265
申请日：2015-11-03
申请人： Isis Innovation Ltd. , Government of the USA, as represented by the Secretary, Department of Health and Human Services
发明人： Kieran Clarke , Richard Lewis Veech
IPC分类号： A61K31/22 , A61K45/06 , A61K9/00
CPC分类号： A61K31/22 , A61K9/0053 , A61K31/047 , A61K31/19 , A61K31/365 , A61K45/06 , A61P3/06 , A61P3/10 , A61K2300/00
摘要： The subject disclosure provides compositions for reducing serum cholesterol and/or triglyceride levels in subjects. These compositions can comprise racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol or R-1,3 butandiol alone and can be, optionally, administered in conjunction with a low fat diet to a subject. Alternatively, compositions comprising racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol, R-1,3 butandiol or combinations thereof can be formulated as nutritional supplements (also referred to as nutritional compositions) or incorporated into therapeutic compositions containing a) anti-hypertensive agents; b) anti-inflammatory agents; c) glucose lowering agents; or d) anti-lipemic agents) which are administered to a subject, optionally in combination with a low fat diet, in order to cause a reduction or lowering of: serum cholesterol levels; triglyceride levels; serum glucose levels, serum homocysteine levels, inflammatory proteins (e.g., C reactive protein) and/or hypertension in treated subjects. Alternatively, compositions disclosed herein can be administered alone, or in combination with other therapeutic agents to prevent or reverse vascular disease.
摘要翻译：本公开提供了用于降低受试者的血清胆固醇和/或甘油三酯水平的组合物。这些组合物可以包含外消旋的β-羟基丁酸酯或任选呈酸形式的D-和β-二羟基丁酸酯，外消旋和β-羟基丁酸酯或D-羟基丁酸酯的生理上相容的盐，D-和bgr-羟基丁酸酯，低聚物含有2-20个或更多个直链或环状单体单元的D-和bgr-羟基丁酸酯，外消旋1,3-丁二醇或单独的R-1,3-丁二醇，并且可任选地与低脂肪饮食到一个主题。或者，包含外消旋的β-羟基丁酸酯或D-半乳糖 - 羟基丁酸酯，任选地为酸形式的外消旋和β-羟基丁酸酯或D-羟基丁酸酯的生理上相容的盐，D-和β-羟基丁酸酯，低聚物含有2-20个或更多个直链或环状单体单元的D-和bgr-羟基丁酸酯，外消旋1,3-丁二醇，R-1,3-丁二醇或其组合可以配制成营养补充剂（也称营养组合物）或掺入含有a）抗高血压药物的治疗组合物; b）抗炎剂; c）葡萄糖降低剂; 或d）抗血脂剂），其被施用于受试者，任选地与低脂肪饮食组合，以引起血清胆固醇水平的降低或降低; 甘油三酯水平; 血清葡萄糖水平，血清同型半胱氨酸水平，炎症蛋白质（例如C反应蛋白）和/或治疗对象的高血压。或者，本文公开的组合物可以单独施用，或与其它治疗剂组合施用以预防或逆转血管疾病。

4. 发明申请

US20230075547A1 KETONE BODIES AND KETONE BODY ESTERS AS BLOOD LIPID LOWERING AGENTS 有权
公开(公告)号：US20230075547A1
公开(公告)日：2023-03-09
申请号：US17728600
申请日：2022-04-25
申请人： OXFORD UNIVERSITY INNOVATION LIMITED , Government of the USA, as represented by the Secretary, Department of Health and Human Services
发明人： Kieran Clarke , Richard Lewis Veech
IPC分类号： A61K31/22 , A61P3/10 , A61P3/06 , A61K31/047 , A61K31/19 , A61K31/365 , A61K45/06 , A61K9/00
摘要： The subject disclosure provides compositions for reducing serum cholesterol and/or triglyceride levels in subjects. These compositions can comprise racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol or R-1,3 butandiol alone and can be, optionally, administered in conjunction with a low fat diet to a subject. Alternatively, compositions comprising racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol, R-1,3 butandiol or combinations thereof can be formulated as nutritional supplements (also referred to as nutritional compositions) or incorporated into therapeutic compositions containing a) anti-hypertensive agents; b) anti-inflammatory agents; c) glucose lowering agents; or d) anti-lipemic agents) which are administered to a subject, optionally in combination with a low fat diet, in order to cause a reduction or lowering of: serum cholesterol levels; triglyceride levels; serum glucose levels, serum homocysteine levels, inflammatory proteins (e.g., C reactive protein) and/or hypertension in treated subjects. Alternatively, compositions disclosed herein can be administered alone, or in combination with other therapeutic agents to prevent or reverse vascular disease.

5. 发明申请

US20190201366A1 KETONE BODIES AND KETONE BODY ESTERS AS BLOOD LIPID LOWERING AGENTS 审中-公开
公开(公告)号：US20190201366A1
公开(公告)日：2019-07-04
申请号：US16203748
申请日：2018-11-29
申请人： OXFORD UNIVERSITY INNOVATION LIMITED , Government of the USA, as represented by the Secretary, Department of Health and Human Services
发明人： Kieran Clarke , Richard Lewis Veech
IPC分类号： A61K31/22 , A61K45/06 , A61K31/365 , A61K31/047 , A61P3/10 , A61K31/19 , A61P3/06 , A61K9/00
CPC分类号： A61K31/22 , A61K9/0053 , A61K31/047 , A61K31/19 , A61K31/365 , A61K45/06 , A61P3/06 , A61P3/10 , A61K2300/00
摘要： The subject disclosure provides compositions for reducing serum cholesterol and/or triglyceride levels in subjects. These compositions can comprise racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol or R-1,3 butandiol alone and can be, optionally, administered in conjunction with a low fat diet to a subject. Alternatively, compositions comprising racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol, R-1,3 butandiol or combinations thereof can be formulated as nutritional supplements (also referred to as nutritional compositions) or incorporated into therapeutic compositions containing a) anti-hypertensive agents; b) anti-inflammatory agents; c) glucose lowering agents; or d) anti-lipemic agents) which are administered to a subject, optionally in combination with a low fat diet, in order to cause a reduction or lowering of: serum cholesterol levels; triglyceride levels; serum glucose levels, serum homocysteine levels, inflammatory proteins (e.g., C reactive protein) and/or hypertension in treated subjects. Alternatively, compositions disclosed herein can be administered alone, or in combination with other therapeutic agents to prevent or reverse vascular disease.

6. 发明申请

US20140194509A1 HYDROXYBUTYRATE ESTER AND MEDICAL USE THEREOF 审中-公开
标题翻译：羟基丁酸酯及其医疗用途
公开(公告)号：US20140194509A1
公开(公告)日：2014-07-10
申请号：US14101834
申请日：2013-12-10
申请人： Government of the USA, as Represented by the Secretary, Department of Health and Human Services , Isis Innovation Limited
发明人： Kieran Clarke , Richard Lewis Veech
IPC分类号： C07C69/675 , A23L2/52 , A23L1/30
CPC分类号： A23L2/52 , A23L33/10 , A23V2002/00 , A61K31/22 , C07B2200/07 , C07C69/675 , A23V2200/316 , A23V2200/322 , A23V2200/328 , A23V2250/30
摘要： A compound which is 3-hydroxybutyl 3-hydroxybutyrate enantiomerically enriched with respect to (3R)-hydroxybutyl (3R)-hydroxybutyrate of formula (I) is an effective and palatable precursor to the ketone body (3R)-hydroxybutyrate and may therefore be used to treat a condition which is caused by, exacerbated by or associated with elevated plasma levels of free fatty acids in a human or animal subject, for instance a condition where weight loss or weight gain is implicated, or to promote alertness or improve cognitive function, or to treat, prevent or reduce the effects of neurodegeneration, free radical toxicity, hypoxic conditions or hyperglycaemia.
摘要翻译：对于式（I）的（3R） - 羟基丁酸（3R） - 羟基丁酸酯，对映体富集3-羟基丁酸3-羟基丁酯的化合物是酮体（3R） - 羟基丁酸酯的有效和可口的前体，因此可以使用治疗由人或动物受试者的游离脂肪酸的血浆水平升高或与之相关的病症，例如涉及体重减轻或体重增加的病症，或促进警觉性或改善认知功能，或治疗，预防或减少神经变性，自由基毒性，缺氧条件或高血糖症的作用。

7. 发明申请

US20210015730A1 COMPOUND FOR USE IN PROTECTING SKIN 有权
公开(公告)号：US20210015730A1
公开(公告)日：2021-01-21
申请号：US17032616
申请日：2020-09-25
申请人： TDELTAS LIMITED , GOVERNMENT OF THE USA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
发明人： Kieran Clarke , Richard Lewis Veech
IPC分类号： A61K8/37 , A61Q19/00 , A61Q19/08 , A61Q17/04 , A61K31/22 , A61K9/06 , A61K9/00 , A61K47/10 , A61K31/357 , A61K8/86 , A61Q17/00
摘要： A method of protecting animal tissue particularly skin, from damage caused by radiation exposure, by contacting the tissue with a ketone ester, a method of protecting skin, reducing the deterioration of skin or maintaining or improving the properties of skin by applying topically to the skin a ketone body comprising (R)-3-hydroxybutyrate moieties is disclosed. A ketone body comprising (R)-3-hydroxybutyrate moieties, especially enantiomerically enriched R-1,3-hydroxybutyl-(R)-3-hydroxybutyrate, for such uses is also provided.

8. 发明授权

US11311509B2 Ketone bodies and ketone body esters as blood lipid lowering agents 有权
公开(公告)号：US11311509B2
公开(公告)日：2022-04-26
申请号：US16203748
申请日：2018-11-29
申请人： OXFORD UNIVERSITY INNOVATION LIMITED , Government of the USA, as represented by the Secretary, Department of Health and Human Services
发明人： Kieran Clarke , Richard Lewis Veech
IPC分类号： A61K31/22 , A61P3/10 , A61P3/06 , A61K31/047 , A61K31/19 , A61K31/365 , A61K45/06 , A61K9/00
摘要： The subject disclosure provides compositions for reducing serum cholesterol and/or triglyceride levels in subjects. These compositions can comprise racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol or R-1,3 butandiol alone and can be, optionally, administered in conjunction with a low fat diet to a subject. Alternatively, compositions comprising racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol, R-1,3 butandiol or combinations thereof can be formulated as nutritional supplements (also referred to as nutritional compositions) or incorporated into therapeutic compositions containing a) anti-hypertensive agents; b) anti-inflammatory agents; c) glucose lowering agents; or d) anti-lipemic agents) which are administered to a subject, optionally in combination with a low fat diet, in order to cause a reduction or lowering of: serum cholesterol levels; triglyceride levels; serum glucose levels, serum homocysteine levels, inflammatory proteins (e.g., C reactive protein) and/or hypertension in treated subjects. Alternatively, compositions disclosed herein can be administered alone, or in combination with other therapeutic agents to prevent or reverse vascular disease.

9. 发明授权

US10154982B2 Ketone bodies and ketone body esters as blood lipid lowering agents 有权
公开(公告)号：US10154982B2
公开(公告)日：2018-12-18
申请号：US14931265
申请日：2015-11-03
申请人： Isis Innovation Ltd. , The United States of America, as represented by the Secretary, Department of Health and Human Services
发明人： Kieran Clarke , Richard Lewis Veech
IPC分类号： A61K31/22 , A61P3/06 , A61P3/10 , A61K31/047 , A61K31/19 , A61K31/365 , A61K45/06 , A61K9/00
摘要： The subject disclosure provides compositions for reducing serum cholesterol and/or triglyceride levels in subjects. These compositions can comprise racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol or R-1,3 butandiol alone and can be, optionally, administered in conjunction with a low fat diet to a subject. Alternatively, compositions comprising racemic β-hydroxybutyrate or D-β-hydroxybutyrate, optionally in the acid form, physiologically compatible salts of racemic β-hydroxybutyrate or D-β-hydroxybutyrate, esters of D-β-hydroxybutyrate, oligomers of D-β-hydroxybutyrate containing from 2 to 20 or more monomeric units in either linear or cyclic form, racemic 1,3 butandiol, R-1,3 butandiol or combinations thereof can be formulated as nutritional supplements (also referred to as nutritional compositions) or incorporated into therapeutic compositions containing a) anti-hypertensive agents; b) anti-inflammatory agents; c) glucose lowering agents; or d) anti-lipemic agents) which are administered to a subject, optionally in combination with a low fat diet, in order to cause a reduction or lowering of: serum cholesterol levels; triglyceride levels; serum glucose levels, serum homocysteine levels, inflammatory proteins (e.g., C reactive protein) and/or hypertension in treated subjects. Alternatively, compositions disclosed herein can be administered alone, or in combination with other therapeutic agents to prevent or reverse vascular disease.

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