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1. 发明授权

US06670484B2 Process for the production of r(+)&agr;-lipoic acid 有权
标题翻译：生产r（+）α-硫辛酸的方法
公开(公告)号：US06670484B2
公开(公告)日：2003-12-30
申请号：US10398892
申请日：2003-04-09
申请人： Flavio Villani , Antonio Nardi , Annibale Salvi , Giovanna Falabella
发明人： Flavio Villani , Antonio Nardi , Annibale Salvi , Giovanna Falabella
IPC分类号： C07D33902
CPC分类号： C07D339/04 , C07C319/06 , C07C323/60
摘要： Process for the synthesis of R(+)&agr;-lipoic acid comprising the following stages: a) Salifying of racemic thioctic acid with R(+)&agr;-methylbenzylamine; b) separation by filtration of the crystallized diastereoisomeric salt of R(+)&agr;-lipoic acid-R(+)&agr;-methylbenzylamine; c) purification by re-crystallization of the diastereoisomeric salt of R(+) &agr;-lipoic acid-R(+)&agr;-methylbenzylamine, in which the re-crystallization solvent consists of a mixture of non-polar/polar solvents; d) separation of the diastereoisomeric salt to obtain R(+)&agr;-lipoic acid by reaction of said salt with acids selected from the group consisting of aliphatic hydroxy-carboxylic acids having 3 to 6 carbon atoms and aqueous phosphoric acid.
摘要翻译：包括以下阶段的R（+）α-硫辛酸的合成方法：a）用R（+） - α-甲基苄胺磺化外消旋硫辛酸; b）通过过滤R（+）α-硫辛酸-R（+）α-甲基苄胺的结晶非对映异构体盐分离; c）通过R（+）α-硫辛酸-R（+）α-甲基苄胺的非对映异构体盐的重结晶进行纯化，其中重结晶溶剂由非极性/极性溶剂的混合物组成; d）通过所述盐与选自具有3至6个碳原子的脂肪族羟基羧酸和磷酸水溶液的酸反应，分离非对映异构盐以获得R（+）α-硫辛酸。

2. 发明授权

US06864374B2 Synthesis of r(+)α-lipoic acid 有权
标题翻译： r（+）α-硫辛酸的合成
公开(公告)号：US06864374B2
公开(公告)日：2005-03-08
申请号：US10398890
申请日：2001-10-08
申请人： Flavio Villani , Antonio Nardi , Annibale Salvi , Giovanna Falabella
发明人： Flavio Villani , Antonio Nardi , Annibale Salvi , Giovanna Falabella
IPC分类号： C07B53/00 , C07B57/00 , C07B61/00 , C07C51/41 , C07C51/487 , C07C53/19 , C07C67/08 , C07C69/63 , C07D339/04 , C07D339/02
CPC分类号： C07D339/04
摘要： Process for the synthesis of R(+)α-lipoic acid comprising the following stages: a) Salifying of racemic 6,8-halo-octanoic acid with S(−)α-methylbenzylamine; b) separation by filtration of the crystallized diastereoisomeric salt of R(+)6,8-di-halo-octanoic acid-S(−)α-methylbenzylamine; c) purification by re-crystallization of the diastereoisomeric salt of R(+)6,8-di-halo-octanoic acid-S(−)α-methylbenzylamine; (d) separation of the diastereoisomeric salt to obtain R(+)6,8-di-halo-octanoic acid by reation of said salt with strong mineral acids in an aqueous solution with a dilution between 2 and 10% by weight; e) esterification of R(+)6,8-di-halo-octanoic acid to obtain the corresponding alkyl ester; f) reaction of the alkyl ester of R(+)6,8-di-halo-octanoic acid in an organic solvent with an aqueous solution of alkali disulfide in presence of a compound for phase transfer catalysis; g) hydolysis of the ester of R(+)α-lipoic acid.
摘要翻译：包括以下步骤的合成R（+）α-硫辛酸的方法：a）用S（ - ） - α-甲基苄胺磺化外消旋6,8-辛酸; b）通过过滤R（+）6,8-二卤代辛酸-S（ - ）α-甲基苄胺的结晶非对映异构体盐分离; c）通过R（+）6,8-二 - 卤代 - 辛酸-S（ - ） - α-甲基苄胺的非对映异构体盐的重结晶进行纯化; （d）通过用强无机酸在稀释在2至10重量％之间的水溶液中重复所述盐，分离非对映异构盐以获得R（+）6,8-二卤代辛酸; e）R（+）6,8-二卤代辛酸酯化得到相应的烷基酯; f）在相转移催化化合物存在下，R（+）6,8-二卤代辛酸烷基酯在有机溶剂中与碱性二硫化物水溶液的反应; g）R（+）α-硫辛酸的酯的水解。

3. 发明授权

US08722096B2 Lipoic acid pellets 失效
标题翻译：硫辛酸颗粒
公开(公告)号：US08722096B2
公开(公告)日：2014-05-13
申请号：US12302260
申请日：2007-05-25
申请人： Luigi Boltri , Flavio Fabiani , Luigi Mapelli , Annibale Salvi , Paolo Magri' , Antonio Nardi , Flavio Villani
发明人： Luigi Boltri , Flavio Fabiani , Luigi Mapelli , Annibale Salvi , Paolo Magri' , Antonio Nardi , Flavio Villani
IPC分类号： A61K9/16 , A61K9/50 , C07D339/04
CPC分类号： C07D339/04 , A23L33/10 , A61K9/1652 , A61K9/5042 , A61K9/5047 , A61K9/5078 , A61K31/385
摘要： Lipoic acid pellets are described, obtained from inert cores externally coated with lipoic acid. The so obtained active cores are coated with a first layer of insulating polymeric material and then with a polymeric coat that is insoluble at the gastric pH. Pellet are then formulated pharmaceutically, for instance in jelly capsules or controlled release capsules or as oral suspensions, dispersible powders, sachets, etc.
摘要翻译：描述了由外部涂覆有硫辛酸的惰性核获得的硫辛酸颗粒。如此获得的活性芯被第一层绝缘聚合物材料涂覆，然后用不溶于胃pH的聚合物涂层涂覆。然后将丸剂药物配制，例如在胶囊或控释胶囊中，或作为口服悬浮液，可分散粉末，小药膏等。

4. 发明申请

US20090117232A1 LIPOIC ACID PELLETS 失效
公开(公告)号：US20090117232A1
公开(公告)日：2009-05-07
申请号：US12302260
申请日：2007-05-25
申请人： Luigi Boltri , Flavio Fabiani , Luigi Mapelli , Annibale Salvi , Paolo Magri' , Antonio Nardi , Flavio Villani
发明人： Luigi Boltri , Flavio Fabiani , Luigi Mapelli , Annibale Salvi , Paolo Magri' , Antonio Nardi , Flavio Villani
IPC分类号： A23L1/30 , A61K31/385 , B05D3/00 , A23L1/29
CPC分类号： C07D339/04 , A23L33/10 , A61K9/1652 , A61K9/5042 , A61K9/5047 , A61K9/5078 , A61K31/385
摘要： Lipoic acid pellets are described, obtained from inert cores externally coated with lipoic acid. The so obtained active cores are coated with a first layer of insulating polymeric material and then with a polymeric coat that is insoluble at the gastric pH. Pellet are then formulated pharmaceutically, for instance in jelly capsules or controlled release capsules or as oral suspensions, dispersible powders, sachets, etc.
摘要翻译：描述了由外部涂覆有硫辛酸的惰性核获得的硫辛酸颗粒。如此获得的活性芯被第一层绝缘聚合物材料涂覆，然后用不溶于胃pH的聚合物涂层涂覆。然后将丸剂药物配制，例如在胶囊或控释胶囊中，或作为口服悬浮液，可分散粉末，小药膏等。

5. 发明授权

US07235582B2 Basic salt of thioctic acid with L-carnitine 有权
标题翻译：硫辛酸与L-肉碱的碱性盐
公开(公告)号：US07235582B2
公开(公告)日：2007-06-26
申请号：US10698451
申请日：2003-11-03
申请人： Annibale Salvi , Flavio Villani , Antonio Nardi , Bruno De Angelis
发明人： Annibale Salvi , Flavio Villani , Antonio Nardi , Bruno De Angelis
IPC分类号： A61K31/385 , A61K31/195 , C07D339/04
CPC分类号： C07D339/04 , A23L33/10 , A23V2002/00 , A23V2250/026 , A23V2250/0612
摘要： Salt of thioctic acid with L-carnitine with the formula: AY(X)x where A is where Y is the cation of an alkaline metal, of an alkaline earth metal or is a quaternary ammonium group, X is A or OH−, x is equal to 0 when Y is the cation of an alkaline metal or a quaternary ammonium group and equal to 1 when Y is an alkaline earth metal.
摘要翻译：硫辛酸与左旋肉碱的盐，具有下式：<？in-line-formula description =“In-line Formulas”end =“lead”？> AY（X） line-formula description =“In-line Formulas”end =“tail”？>其中A是碱金属阳离子，碱土金属或季铵基，X是A或OH

6. 发明授权

US09820948B2 Lipoic acid pellet composition 有权
公开(公告)号：US09820948B2
公开(公告)日：2017-11-21
申请号：US12739449
申请日：2008-10-23
申请人： Paolo Magri' , Antonio Nardi , Annibale Salvi , Flavio Villani
发明人： Paolo Magri' , Antonio Nardi , Annibale Salvi , Flavio Villani
IPC分类号： A61K31/385 , A61K9/48 , A61K31/202 , A61K9/50
CPC分类号： A61K9/4875 , A61K9/4808 , A61K9/5078 , A61K31/202
摘要： The present invention concerns a new composition based on pellets of lipoic acid in a lipophilic medium, if necessary combined with other active ingredients.

7. 发明申请

US20140309293A1 CRYSTALLINE FORM 审中-公开
标题翻译：结晶形式
公开(公告)号：US20140309293A1
公开(公告)日：2014-10-16
申请号：US14131746
申请日：2012-07-06
申请人： Antonio Nardi , Annibale Salvi , Flavio Villani , Bruno De Angelis , Giorgio Bertolini
发明人： Antonio Nardi , Annibale Salvi , Flavio Villani , Bruno De Angelis , Giorgio Bertolini
IPC分类号： C07D339/04 , A61K31/381
CPC分类号： C07D339/04 , A61K31/381
摘要： The invention concerns a new polymorphic form of R-(+)-α-lipoic acid and a process for the preparation thereof, in addition to the compositions that contain it and its use as a medicine or food supplement.
摘要翻译：本发明涉及新的多晶型的R - （+） - α-硫辛酸及其制备方法，除了含有它的组合物及其作为药物或食品补充剂的用途。

8. 发明申请

US20110129442A1 LIPOIC ACID PELLET COMPOSITION 有权
公开(公告)号：US20110129442A1
公开(公告)日：2011-06-02
申请号：US12739449
申请日：2008-10-23
申请人： Paolo Magri' , Antonio Nardi , Annibale Salvi , Flavio Villani
发明人： Paolo Magri' , Antonio Nardi , Annibale Salvi , Flavio Villani
IPC分类号： A61K31/385 , A61K31/675 , A61K31/41 , A61K38/21 , A61K31/57 , A61P39/06
CPC分类号： A61K9/4875 , A61K9/4808 , A61K9/5078 , A61K31/202
摘要： The present invention concerns a new composition based on pellets of lipoic acid in a lipophilic medium, if necessary combined with other active ingredients.
摘要翻译：本发明涉及一种基于在亲脂性介质中硫辛酸颗粒的新组合物，如果需要，可与其它活性成分组合。

9. 发明申请

US20110015269A1 PROCESS FOR THE PREPARATION OF DIACERIN 失效
标题翻译：制备DIACERIN的方法
公开(公告)号：US20110015269A1
公开(公告)日：2011-01-20
申请号：US12811423
申请日：2008-12-19
申请人： Annibale Salvi , Antonio Nardi , Stefano Maiorana , Mara Sada
发明人： Annibale Salvi , Antonio Nardi , Stefano Maiorana , Mara Sada
IPC分类号： A61K31/222 , C07C50/34
CPC分类号： C07C66/02 , C07C67/24 , C07C2603/24 , C07C69/16
摘要： The invention concerns a new process for the preparation of high purity diacerein, by oxidisation of the protected aloe-emodin in the presence of an oxidising system and radical catalyst and subsequent substitution of the protector groups with acetyl groups.
摘要翻译：本发明涉及通过在氧化系统和自由基催化剂的存在下氧化保护的芦荟大黄素并随后用保护基团用乙酰基取代来制备高纯度双醋瑞因的新方法。

10. 发明申请

US20110182953A1 POLYMORPHIC FORM OF CALCIUM ACAMPROSATE 审中-公开
标题翻译：钙磷酸钙的多晶型
公开(公告)号：US20110182953A1
公开(公告)日：2011-07-28
申请号：US13120992
申请日：2009-09-04
申请人： Annibale Salvi , Antonio Nardi , Bruno De Angelis
发明人： Annibale Salvi , Antonio Nardi , Bruno De Angelis
IPC分类号： A61K9/00 , C07C309/15 , A61K31/185 , A61P25/32
CPC分类号： C07C309/15 , A61K31/185 , C07B2200/13
摘要： The present invention relates to a new polymorphic form of calcium acetyl-homotaurinate, designated as form B, and processes for the preparation of said form B and of the known crystalline form.
摘要翻译：本发明涉及一种新的多形态的乙酰 - 同三酸三钙，称为B型，以及制备所述形式B和已知结晶形式的方法。

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