CA2468234C - Acetyl l-carnitine fumarate and process for preparing the same - Google Patents
Acetyl l-carnitine fumarate and process for preparing the same Download PDFInfo
- Publication number
- CA2468234C CA2468234C CA2468234A CA2468234A CA2468234C CA 2468234 C CA2468234 C CA 2468234C CA 2468234 A CA2468234 A CA 2468234A CA 2468234 A CA2468234 A CA 2468234A CA 2468234 C CA2468234 C CA 2468234C
- Authority
- CA
- Canada
- Prior art keywords
- acetyl
- carnitine
- solution
- crystalline
- acid fumarate
- 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
- 238000004519 manufacturing process Methods 0.000 title abstract description 10
- FXMGCAULAFEKSO-SBSPUUFOSA-N C(C=CC(=O)O)(=O)O.C(C)(=O)[C@](O)(C[N+](C)(C)C)CC([O-])=O Chemical compound C(C=CC(=O)O)(=O)O.C(C)(=O)[C@](O)(C[N+](C)(C)C)CC([O-])=O FXMGCAULAFEKSO-SBSPUUFOSA-N 0.000 title description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 abstract description 41
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 abstract description 35
- 239000002253 acid Substances 0.000 abstract description 28
- 239000000126 substance Substances 0.000 abstract description 28
- RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 abstract description 26
- 239000007787 solid Substances 0.000 abstract description 18
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 239000012297 crystallization seed Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 230000001376 precipitating effect Effects 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 8
- -1 2-(acetyloxy)-3-carboxy-N,N,N-trimethyl-l-propanaminium ions Chemical class 0.000 description 7
- 239000001530 fumaric acid Substances 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000010413 mother solution Substances 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 229940085605 saccharin sodium Drugs 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- RZALONVQKUWRRY-XOJLQXRJSA-N (2r,3r)-2,3-dihydroxybutanedioate;hydron;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O RZALONVQKUWRRY-XOJLQXRJSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- QWYFHHGCZUCMBN-SECBINFHSA-N O-butanoyl-L-carnitine Chemical class CCCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C QWYFHHGCZUCMBN-SECBINFHSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000008040 ionic compounds Chemical class 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000006082 mold release agent Substances 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical class O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/02—Preparation of carboxylic acid esters by interreacting ester groups, i.e. transesterification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Vascular Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001RM000729A ITRM20010729A1 (it) | 2001-12-12 | 2001-12-12 | Sale di acetil l-carnitina con un acido organico dicarbossilico e procedimento per la sua preparazione. |
| ITRM2001A000729 | 2001-12-12 | ||
| PCT/IT2002/000743 WO2003053911A1 (en) | 2001-12-12 | 2002-11-25 | Acetyl l-carnitine salt with a dicarboxilic organic acid and process for preparing same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2468234A1 CA2468234A1 (en) | 2003-07-03 |
| CA2468234C true CA2468234C (en) | 2010-02-23 |
Family
ID=11455916
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2468234A Expired - Fee Related CA2468234C (en) | 2001-12-12 | 2002-11-25 | Acetyl l-carnitine fumarate and process for preparing the same |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6673837B2 (enExample) |
| EP (1) | EP1453791B1 (enExample) |
| JP (1) | JP4902940B2 (enExample) |
| KR (1) | KR100860386B1 (enExample) |
| CN (1) | CN1250521C (enExample) |
| AT (1) | ATE457300T1 (enExample) |
| AU (1) | AU2002358989A1 (enExample) |
| CA (1) | CA2468234C (enExample) |
| CY (1) | CY1110684T1 (enExample) |
| DE (1) | DE60235318D1 (enExample) |
| DK (1) | DK1453791T3 (enExample) |
| ES (1) | ES2339432T3 (enExample) |
| HU (1) | HU230034B1 (enExample) |
| IT (1) | ITRM20010729A1 (enExample) |
| PL (1) | PL207877B1 (enExample) |
| PT (1) | PT1453791E (enExample) |
| SI (1) | SI1453791T1 (enExample) |
| WO (1) | WO2003053911A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8173618B2 (en) * | 2003-07-25 | 2012-05-08 | University Of Massachusetts | Formulations for reducing neuronal degeneration |
| CN101209975B (zh) * | 2006-12-29 | 2010-12-01 | 沈阳科硕营养科技有限公司 | 左旋肉碱富马酸钙及其制备方法与用途 |
| US8597640B2 (en) * | 2007-10-31 | 2013-12-03 | University Of Massachusetts Lowell | Over-the-counter vitamin/nutriceutical formulation that provides neuroprotection and maintains or improves cognitive performance in alzheimer's disease and normal aging |
| JP2012092036A (ja) * | 2010-10-26 | 2012-05-17 | Mitsubishi Rayon Co Ltd | カルニチンの塩の製造方法 |
| JP2014525324A (ja) * | 2011-08-31 | 2014-09-29 | ザ プロクター アンド ギャンブル カンパニー | 接着された強化層を有するファスニング部材 |
| JP5933383B2 (ja) * | 2012-07-26 | 2016-06-08 | ロート製薬株式会社 | 内服用固形製剤の吸湿性・流動性の改善方法、吸湿性・流動性が改善されてなる内服用固形製剤、及び該内服用固形製剤の製造法 |
| JP6100939B2 (ja) * | 2016-02-26 | 2017-03-22 | ロート製薬株式会社 | 内服用固形製剤の吸湿性・流動性の改善方法、吸湿性・流動性が改善されてなる内服用固形製剤、及び該内服用固形製剤の製造法 |
| JP6964876B2 (ja) * | 2017-11-27 | 2021-11-10 | 株式会社古川リサーチオフィス | オロット酸−カルニチン混合体粉体又はフマル酸−カルニチン混合体粉体の製造方法 |
| CN119351483B (zh) * | 2024-12-03 | 2025-05-30 | 北京佰依源生物科技有限公司 | 一种长碳链二元酸生产强度提高的方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0150688B1 (en) * | 1983-12-28 | 1987-04-22 | Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. | Salts of l-carnitine and alkanoyl l-carnitines and process for preparing same |
-
2001
- 2001-12-12 IT IT2001RM000729A patent/ITRM20010729A1/it unknown
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2002
- 2002-07-31 US US10/207,993 patent/US6673837B2/en not_active Expired - Lifetime
- 2002-11-25 DE DE60235318T patent/DE60235318D1/de not_active Expired - Lifetime
- 2002-11-25 EP EP02793335A patent/EP1453791B1/en not_active Expired - Lifetime
- 2002-11-25 PT PT02793335T patent/PT1453791E/pt unknown
- 2002-11-25 CA CA2468234A patent/CA2468234C/en not_active Expired - Fee Related
- 2002-11-25 PL PL371130A patent/PL207877B1/pl unknown
- 2002-11-25 ES ES02793335T patent/ES2339432T3/es not_active Expired - Lifetime
- 2002-11-25 WO PCT/IT2002/000743 patent/WO2003053911A1/en not_active Ceased
- 2002-11-25 AT AT02793335T patent/ATE457300T1/de active
- 2002-11-25 JP JP2003554628A patent/JP4902940B2/ja not_active Expired - Fee Related
- 2002-11-25 AU AU2002358989A patent/AU2002358989A1/en not_active Abandoned
- 2002-11-25 SI SI200230893T patent/SI1453791T1/sl unknown
- 2002-11-25 KR KR1020047008307A patent/KR100860386B1/ko not_active Expired - Fee Related
- 2002-11-25 DK DK02793335.7T patent/DK1453791T3/da active
- 2002-11-25 HU HU0402545A patent/HU230034B1/hu not_active IP Right Cessation
- 2002-11-25 CN CNB028248260A patent/CN1250521C/zh not_active Expired - Fee Related
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- 2010-04-27 CY CY20101100377T patent/CY1110684T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1602294A (zh) | 2005-03-30 |
| KR20040064721A (ko) | 2004-07-19 |
| HU230034B1 (hu) | 2015-05-28 |
| WO2003053911A1 (en) | 2003-07-03 |
| JP2005513122A (ja) | 2005-05-12 |
| HK1073295A1 (en) | 2005-09-30 |
| HUP0402545A3 (en) | 2012-09-28 |
| ITRM20010729A1 (it) | 2003-06-12 |
| JP4902940B2 (ja) | 2012-03-21 |
| DK1453791T3 (da) | 2010-05-25 |
| PL371130A1 (en) | 2005-06-13 |
| HUP0402545A2 (hu) | 2005-04-28 |
| ATE457300T1 (de) | 2010-02-15 |
| EP1453791B1 (en) | 2010-02-10 |
| PT1453791E (pt) | 2010-04-14 |
| CY1110684T1 (el) | 2015-06-10 |
| CN1250521C (zh) | 2006-04-12 |
| SI1453791T1 (sl) | 2010-11-30 |
| US20030119904A1 (en) | 2003-06-26 |
| DE60235318D1 (de) | 2010-03-25 |
| CA2468234A1 (en) | 2003-07-03 |
| US6673837B2 (en) | 2004-01-06 |
| ES2339432T3 (es) | 2010-05-20 |
| AU2002358989A1 (en) | 2003-07-09 |
| KR100860386B1 (ko) | 2008-09-26 |
| PL207877B1 (pl) | 2011-02-28 |
| EP1453791A1 (en) | 2004-09-08 |
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