CA2265276C - Modified enantiomer content of crystalline alpha-lipoic acid (rs-thioctic acid) - Google Patents
Modified enantiomer content of crystalline alpha-lipoic acid (rs-thioctic acid) Download PDFInfo
- Publication number
- CA2265276C CA2265276C CA002265276A CA2265276A CA2265276C CA 2265276 C CA2265276 C CA 2265276C CA 002265276 A CA002265276 A CA 002265276A CA 2265276 A CA2265276 A CA 2265276A CA 2265276 C CA2265276 C CA 2265276C
- Authority
- CA
- Canada
- Prior art keywords
- thioctic acid
- acid
- enantiomers
- thioctic
- proportions
- 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.)
- Expired - Fee Related
Links
- 229960002663 thioctic acid Drugs 0.000 title claims abstract description 82
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 235000019136 lipoic acid Nutrition 0.000 title claims abstract description 57
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims abstract description 67
- 239000000843 powder Substances 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 20
- 238000002844 melting Methods 0.000 claims description 15
- 230000008018 melting Effects 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 7
- 125000001931 aliphatic group Chemical group 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000008240 homogeneous mixture Substances 0.000 claims description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 4
- 230000003502 anti-nociceptive effect Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- 239000002537 cosmetic Substances 0.000 claims description 3
- 230000001120 cytoprotective effect Effects 0.000 claims description 3
- 201000002342 diabetic polyneuropathy Diseases 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 235000016709 nutrition Nutrition 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000012986 modification Methods 0.000 abstract description 13
- 230000004048 modification Effects 0.000 abstract description 13
- 239000000243 solution Substances 0.000 description 11
- 239000013078 crystal Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- -1 pyruvic acid) Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- QVJPPFAOCXDDPW-UHFFFAOYSA-N 5-[chloro(difluoro)methyl]-1,2-oxazole Chemical compound FC(F)(Cl)C1=CC=NO1 QVJPPFAOCXDDPW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 102000012751 Pyruvate Dehydrogenase Complex Human genes 0.000 description 1
- 108010090051 Pyruvate Dehydrogenase Complex Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000005895 oxidative decarboxylation reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/02—Five-membered rings
- C07D339/04—Five-membered rings having the hetero atoms in positions 1 and 2, e.g. lipoic acid
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Seasonings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19810336A DE19810336A1 (de) | 1998-03-11 | 1998-03-11 | Alpha-Liponsäure mit neuartiger Modifikation |
| DE19810336.0 | 1998-03-11 | ||
| US09/074,645 US5994393A (en) | 1998-03-11 | 1998-05-08 | Alpha-lipoic acid with novel modification |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2265276A1 CA2265276A1 (en) | 1999-09-11 |
| CA2265276C true CA2265276C (en) | 2009-09-08 |
Family
ID=26044524
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002265276A Expired - Fee Related CA2265276C (en) | 1998-03-11 | 1999-03-11 | Modified enantiomer content of crystalline alpha-lipoic acid (rs-thioctic acid) |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5994393A (en, 2012) |
| EP (1) | EP0949258B1 (en, 2012) |
| AT (1) | ATE207914T1 (en, 2012) |
| CA (1) | CA2265276C (en, 2012) |
| CY (1) | CY1106435T1 (en, 2012) |
| DE (2) | DE19810336A1 (en, 2012) |
| DK (1) | DK0949258T3 (en, 2012) |
| ES (1) | ES2164474T3 (en, 2012) |
| IN (1) | IN186598B (en, 2012) |
| PT (1) | PT949258E (en, 2012) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19834608A1 (de) * | 1998-07-31 | 2000-02-03 | Basf Ag | Kristallmodifikation der Liponsäure |
| ATE320833T1 (de) * | 2000-06-06 | 2006-04-15 | Verwendung von einem liponsaüren -(r)- enantiomeren in kosmetika und dermatologie | |
| DE10151764A1 (de) * | 2001-10-19 | 2003-05-08 | Basf Ag | Kombination von Liponsäure und Glutamin in Lebens- und Arzneimitteln |
| US20090176864A1 (en) * | 2004-11-24 | 2009-07-09 | Hill's Pet Nutrition, Inc. | Methods For Improving Hepatic and Immune Function In An Animal |
| EP1817058B1 (en) * | 2004-11-24 | 2015-09-02 | Hill's Pet Nutrition, Inc. | Composition for use in improving liver clearance of xenobiotic substances in an animal |
| AU2005322887B2 (en) | 2004-12-30 | 2010-03-11 | Hill's Pet Nutrition, Inc. | Methods for enhancing the quality of life of a senior animal |
| US8252742B2 (en) | 2004-12-30 | 2012-08-28 | Hill's Pet Nutrition, Inc. | Methods for enhancing the quality of life of a senior animal |
| JP2012510511A (ja) * | 2008-12-01 | 2012-05-10 | インヴアスク セラピューテイックス インコーポレイテッド | レニン−アンジオテンシン−アルドステロン系阻害剤及びリポ酸化合物を含有する組成物、並びに、レニン−アンジオテンシン−アルドステロン系に関連した疾患の治療のためのそれらの使用 |
| CN108484570B (zh) * | 2018-05-15 | 2021-05-04 | 苏州富士莱医药股份有限公司 | 一种制备硫辛酸颗粒的方法及设备 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE163849T1 (de) * | 1989-11-09 | 1998-03-15 | Asta Medica Ag | Arzneimittel enthaltend als wirkstoff r-alpha- liponsäure oder s-alpha-liponsäure |
| DE4218572A1 (de) * | 1992-06-05 | 1993-12-09 | Asta Medica Ag | Synergistische Kombination von Arzneimitteln enthaltend als Wirkstoff alpha-Liponsäure, Dihydroliponsäure, deren Metaboliten sowie die oxidierten und reduzierten Enantiomere der alpha-Liponsäure wie die R-alpha-Liponsäure oder S-alpha-Liponsäure sowie Metaboliten der alpha-Liponsäure mit den Vitaminen A, B1-6, B12, C und E |
| DE4235912C2 (de) * | 1992-10-23 | 2002-12-05 | Viatris Gmbh | Verfahren zur Herstellung kristalliner Thioctsäure und deren Verwendung |
| DE4433764A1 (de) * | 1994-09-22 | 1996-03-28 | Asta Medica Ag | Darreichungsformen enthaltend alpha-Liponsäure, feste Salze von R-Thioctsäure mit verbesserter Freisetzung und Bioverfügbarkeit |
-
1998
- 1998-03-11 DE DE19810336A patent/DE19810336A1/de not_active Withdrawn
- 1998-05-08 US US09/074,645 patent/US5994393A/en not_active Expired - Lifetime
-
1999
- 1999-03-02 DE DE59900364T patent/DE59900364D1/de not_active Expired - Lifetime
- 1999-03-02 DK DK99104155T patent/DK0949258T3/da active
- 1999-03-02 AT AT99104155T patent/ATE207914T1/de active
- 1999-03-02 PT PT99104155T patent/PT949258E/pt unknown
- 1999-03-02 EP EP99104155A patent/EP0949258B1/de not_active Expired - Lifetime
- 1999-03-02 ES ES99104155T patent/ES2164474T3/es not_active Expired - Lifetime
- 1999-03-11 CA CA002265276A patent/CA2265276C/en not_active Expired - Fee Related
- 1999-04-06 IN IN317CA1999 patent/IN186598B/en unknown
-
2002
- 2002-01-30 CY CY20021100024T patent/CY1106435T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CY1106435T1 (el) | 2011-04-06 |
| PT949258E (pt) | 2002-04-29 |
| DK0949258T3 (da) | 2002-01-28 |
| CA2265276A1 (en) | 1999-09-11 |
| DE59900364D1 (de) | 2001-12-06 |
| EP0949258A1 (de) | 1999-10-13 |
| ES2164474T3 (es) | 2002-02-16 |
| ATE207914T1 (de) | 2001-11-15 |
| DE19810336A1 (de) | 1999-09-23 |
| US5994393A (en) | 1999-11-30 |
| IN186598B (en, 2012) | 2001-10-06 |
| EP0949258B1 (de) | 2001-10-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130311 |