TWI863930B - 用於製備α-酮戊二酸鈣之方法 - Google Patents
用於製備α-酮戊二酸鈣之方法 Download PDFInfo
- Publication number
- TWI863930B TWI863930B TW108134655A TW108134655A TWI863930B TW I863930 B TWI863930 B TW I863930B TW 108134655 A TW108134655 A TW 108134655A TW 108134655 A TW108134655 A TW 108134655A TW I863930 B TWI863930 B TW I863930B
- Authority
- TW
- Taiwan
- Prior art keywords
- ketoglutaric acid
- water
- ketoglutarate
- calcium
- equivalent
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 159
- LADYPAWUSNPKJF-UHFFFAOYSA-L calcium;2-oxopentanedioate Chemical compound [Ca+2].[O-]C(=O)CCC(=O)C([O-])=O LADYPAWUSNPKJF-UHFFFAOYSA-L 0.000 title claims description 34
- 230000008569 process Effects 0.000 title description 3
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 218
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 claims description 1029
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 498
- HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 claims description 458
- 229940009533 alpha-ketoglutaric acid Drugs 0.000 claims description 458
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical group [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 400
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 395
- 239000000203 mixture Substances 0.000 claims description 359
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 202
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 200
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 196
- 235000017550 sodium carbonate Nutrition 0.000 claims description 196
- -1 alkali metal salt Chemical class 0.000 claims description 58
- 229910052783 alkali metal Inorganic materials 0.000 claims description 52
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 44
- 239000001110 calcium chloride Substances 0.000 claims description 41
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 41
- 235000011148 calcium chloride Nutrition 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 37
- 229910052751 metal Inorganic materials 0.000 claims description 32
- 239000002184 metal Substances 0.000 claims description 32
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical group [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 19
- 238000001035 drying Methods 0.000 claims description 15
- 235000011181 potassium carbonates Nutrition 0.000 claims description 11
- 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 claims description 9
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 9
- VWPLIFKKLCVFCQ-UHFFFAOYSA-L calcium;2-oxopentanedioate;hydrate Chemical compound O.[Ca+2].[O-]C(=O)CCC(=O)C([O-])=O VWPLIFKKLCVFCQ-UHFFFAOYSA-L 0.000 claims description 9
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 9
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 9
- 229910052744 lithium Inorganic materials 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 5
- 239000001639 calcium acetate Substances 0.000 claims description 5
- 235000011092 calcium acetate Nutrition 0.000 claims description 5
- 229960005147 calcium acetate Drugs 0.000 claims description 5
- CBOCVOKPQGJKKJ-UHFFFAOYSA-L Calcium formate Chemical compound [Ca+2].[O-]C=O.[O-]C=O CBOCVOKPQGJKKJ-UHFFFAOYSA-L 0.000 claims description 3
- 229960002713 calcium chloride Drugs 0.000 claims description 3
- 239000004281 calcium formate Substances 0.000 claims description 3
- 229940044172 calcium formate Drugs 0.000 claims description 3
- 235000019255 calcium formate Nutrition 0.000 claims description 3
- 235000011182 sodium carbonates Nutrition 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical class [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 abstract description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 58
- YBGBJYVHJTVUSL-UHFFFAOYSA-L disodium;2-oxopentanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CCC(=O)C([O-])=O YBGBJYVHJTVUSL-UHFFFAOYSA-L 0.000 description 36
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 27
- 239000012535 impurity Substances 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 21
- 239000002244 precipitate Substances 0.000 description 20
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 239000003085 diluting agent Substances 0.000 description 12
- 150000003751 zinc Chemical class 0.000 description 11
- 239000012488 sample solution Substances 0.000 description 10
- 239000012086 standard solution Substances 0.000 description 10
- 238000012546 transfer Methods 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 239000011736 potassium bicarbonate Substances 0.000 description 7
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical group [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- 239000000872 buffer Substances 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 229910001414 potassium ion Inorganic materials 0.000 description 5
- 229910001415 sodium ion Inorganic materials 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 4
- 239000012490 blank solution Substances 0.000 description 4
- PBUBJNYXWIDFMU-UHFFFAOYSA-L calcium;butanedioate Chemical compound [Ca+2].[O-]C(=O)CCC([O-])=O PBUBJNYXWIDFMU-UHFFFAOYSA-L 0.000 description 4
- SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 description 4
- 235000021472 generally recognized as safe Nutrition 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical compound [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 3
- 229910052808 lithium carbonate Inorganic materials 0.000 description 3
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 239000011592 zinc chloride Substances 0.000 description 3
- 235000005074 zinc chloride Nutrition 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000306 component Substances 0.000 description 2
- VTYGSWGUBDXCRA-UHFFFAOYSA-L dipotassium;2-oxopentanedioate Chemical compound [K+].[K+].[O-]C(=O)CCC(=O)C([O-])=O VTYGSWGUBDXCRA-UHFFFAOYSA-L 0.000 description 2
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KAKVUJUFLAFRKG-UHFFFAOYSA-N 2-oxopentanedioic acid;sodium Chemical compound [Na].[Na].OC(=O)CCC(=O)C(O)=O KAKVUJUFLAFRKG-UHFFFAOYSA-N 0.000 description 1
- QNFIHKFBQFJVKV-UHFFFAOYSA-N 5-octoxy-4,5-dioxopentanoic acid Chemical compound CCCCCCCCOC(=O)C(=O)CCC(O)=O QNFIHKFBQFJVKV-UHFFFAOYSA-N 0.000 description 1
- 101710169645 ATP synthase subunit beta Proteins 0.000 description 1
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- TXIXSLPEABAEHP-UHFFFAOYSA-N Dimethyl 2-oxoglutarate Chemical compound COC(=O)CCC(=O)C(=O)OC TXIXSLPEABAEHP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229930195714 L-glutamate Natural products 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000002715 bioenergetic effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- ODBLHEXUDAPZAU-UHFFFAOYSA-N isocitric acid Chemical compound OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000005787 mitochondrial ATP synthesis coupled electron transport Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000021139 traditional diet Nutrition 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/418—Preparation of metal complexes containing carboxylic acid moieties
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/347—Saturated compounds containing more than one carboxyl group containing keto groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Fodder In General (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862736320P | 2018-09-25 | 2018-09-25 | |
| US62/736,320 | 2018-09-25 | ||
| PCT/US2019/052498 WO2020068705A1 (en) | 2018-09-25 | 2019-09-23 | Process of making calcium alpha-ketoglutarate |
| WOPCT/US19/52498 | 2019-09-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW202024013A TW202024013A (zh) | 2020-07-01 |
| TWI863930B true TWI863930B (zh) | 2024-12-01 |
Family
ID=69952136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW108134655A TWI863930B (zh) | 2018-09-25 | 2019-09-25 | 用於製備α-酮戊二酸鈣之方法 |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US11802103B2 (enExample) |
| EP (1) | EP3856166A4 (enExample) |
| JP (1) | JP7499259B2 (enExample) |
| KR (1) | KR102833111B1 (enExample) |
| CN (1) | CN112955139B (enExample) |
| AU (1) | AU2019350699B2 (enExample) |
| BR (1) | BR112021005668A2 (enExample) |
| CA (1) | CA3112205A1 (enExample) |
| CL (1) | CL2021000728A1 (enExample) |
| CO (1) | CO2021004529A2 (enExample) |
| IL (1) | IL281761B2 (enExample) |
| MX (1) | MX2021003482A (enExample) |
| MY (1) | MY203278A (enExample) |
| PE (1) | PE20211816A1 (enExample) |
| PH (1) | PH12021550403A1 (enExample) |
| SG (1) | SG11202102204PA (enExample) |
| TW (1) | TWI863930B (enExample) |
| WO (1) | WO2020068705A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102833111B1 (ko) | 2018-09-25 | 2025-07-10 | 폰세 드 리온 헬스 데지그네이티드 액티비티 컴퍼니 | 칼슘 알파-케토글루타레이트의 제조 방법 |
| CN112941116B (zh) * | 2021-01-04 | 2022-12-02 | 上海朴颐化学科技有限公司 | 一种酶法制备α-酮戊二酸钙的方法 |
| CN114105761B (zh) * | 2021-11-19 | 2024-06-21 | 广东派特埃尔生物科技有限公司 | 一种α-酮戊二酸钠盐的合成工艺 |
| CN115974679A (zh) * | 2022-12-20 | 2023-04-18 | 绍兴市精益生物化工有限公司 | α-酮戊二酸钙盐制备方法 |
| CN119977789A (zh) * | 2025-02-12 | 2025-05-13 | 江苏惠利生物科技有限公司 | 一种离子交换树脂制备高纯度α-酮戊二酸钙的方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102976927A (zh) * | 2012-12-26 | 2013-03-20 | 天津天成制药有限公司 | α-酮戊二酸钙的制备方法 |
Family Cites Families (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2776926A (en) | 1955-08-04 | 1957-01-08 | Eugene S Sharpe | Preparation of alpha-ketoglutaric acid by serratia marcescens |
| US2917528A (en) | 1956-08-24 | 1959-12-15 | Victor Chemical Works | Alkanolaminealkanephosphonic acids and salts thereof |
| US2841616A (en) * | 1956-10-30 | 1958-07-01 | Campbell Soup Co | Process for the recovery of alpha-ketoglutaric acid |
| US3875304A (en) | 1970-04-24 | 1975-04-01 | Schlitz Brewing Co J | Livestock feed composition and method of preparing the same |
| US4045585A (en) | 1976-05-19 | 1977-08-30 | Decel Corporation | Flavored animal food compositions |
| DE3151196A1 (de) * | 1981-12-23 | 1983-06-30 | Kurt Heinz Prof. Dr. 7800 Freiburg Bauer | Verfahren zur herstellung von gut loeslichen 5-aminosalicylsaeure-arzneimittelzubereitungen |
| US6451341B1 (en) | 1990-02-05 | 2002-09-17 | Thomas J. Slaga | Time release formulation of vitamins, minerals and other beneficial supplements |
| US5646187A (en) | 1992-05-20 | 1997-07-08 | Ab Erik Vinnars | Use of alpha-ketoglutarate |
| US6306430B1 (en) | 1998-04-16 | 2001-10-23 | The Iams Company | Process for decreasing adiposity using vitamin a as a dietary supplement |
| US6905707B2 (en) | 1998-05-28 | 2005-06-14 | Medical Research Institute | Controlled release arginine alpha ketoglutarate |
| CO5140079A1 (es) | 1998-10-14 | 2002-03-22 | Novartis Ag | Composicion farmaceutica de liberacion sostenida y metodo para liberar un agente farmaceuticamente activo de liberacion sostenida y metodo para liberar un agente far- maceuticamente activo |
| US6649654B1 (en) | 1999-11-23 | 2003-11-18 | The Regents Of The University Of California | Methods for identifying and using IKK inhibitors |
| AU2002228955B2 (en) | 2000-12-20 | 2005-09-29 | Alcon Inc. | Solution for removing cataracts via liquefracture |
| AU2004237437B2 (en) * | 2003-05-07 | 2011-01-20 | Osteologix A/S | Controlled release composition containing a strontium salt |
| US7589235B2 (en) | 2004-05-06 | 2009-09-15 | Osteologix, A/S | High yield and rapid synthesis methods for producing metallo-organic salts |
| PL368572A1 (en) | 2004-06-17 | 2005-12-27 | Sgp & Sons Ab | Pharmaceutical compound for prevention and therapy of increased level of cholesterol, ldl and triglycerides as well as application of the pharmaceutical compound as an agent acting against atherosclerosis and used in circulatory system affections |
| EP1778616A1 (en) | 2004-08-09 | 2007-05-02 | Cancer Research Technology Limited | Alpha-ketoglutarates and their use as therapeutic agents |
| DK1824470T3 (da) | 2004-12-17 | 2014-08-18 | Cash Alan Brian | Fremgangsmåde til forlængelse af levetiden og forsinke starttidspunktet for alders-relateret sygdom |
| US20060234250A1 (en) | 2005-04-15 | 2006-10-19 | Powers Ralph W Iii | Methods of screening and compositions for life span modulators |
| EP1915144A4 (en) | 2005-06-20 | 2009-08-19 | Accera Inc | METHOD FOR REDUCING OXIDATIVE DAMAGE AND IMPROVING MITOCHONDRIA EFFICIENCY |
| WO2007053943A1 (en) | 2005-11-08 | 2007-05-18 | Multi Formulations Ltd. | The use of compositions comprising ketoacids and amino acids for increasing muscle mass and muscle performance |
| US8367121B2 (en) | 2005-11-23 | 2013-02-05 | Florida A & M University | Nutraceutical agent for attenuating the neurodegenerative process associated with Parkinson's disease |
| PL379512A1 (pl) | 2006-04-21 | 2007-10-29 | Sgp & Sons Ab | Nowe metody i ich zastosowanie |
| PL226695B1 (pl) | 2006-07-03 | 2017-08-31 | Danuta Kruszewska | Środek do zastosowania w zapobieganiu i/lub hamowaniu kolonizacji Helicobacter pylori, zastosowanie soli kwasu alfa‑ketoglutarowego z metalami alkalicznymi i ziem alkalicznych do wytwarzania środka leczniczego oraz dodatku do żywności do zapobiegania i/lub hamowania kolonizacji Helicobacter pylori |
| JP2010522190A (ja) | 2007-03-19 | 2010-07-01 | メタプロテオミクス， エルエルシー | 骨及び関節の健康を助成するための方法と組成物 |
| MX2009013937A (es) | 2007-07-02 | 2010-04-30 | Entress Ab | Nuevo uso de compuestos quimicos farmacologicamente activos conocidos. |
| EP2033623A1 (en) | 2007-09-07 | 2009-03-11 | Cutech S.R.L. | Compositions comprising ornithine ketoglutarate (OKG) |
| JP5406643B2 (ja) | 2008-09-22 | 2014-02-05 | 日本合成化学工業株式会社 | α−オキソカルボン酸の金属塩の製造方法 |
| CN101759553A (zh) | 2008-11-21 | 2010-06-30 | 扬子江药业集团北京海燕药业有限公司 | α-酮酸钙的制备方法 |
| DE102009016119A1 (de) | 2009-04-03 | 2010-10-14 | Evonik Degussa Gmbh | Nahrungsergänzungsmittel enthaltend alpha-Ketosäuren zur Unterstützung der Diabetestherapie |
| BRPI1010655A2 (pt) | 2009-04-10 | 2019-09-03 | Qi Haiyan | novos agentes antienvelhecimento e métodos para identificá-los |
| CN102481271A (zh) | 2009-05-11 | 2012-05-30 | 博格生物系统有限责任公司 | 利用表观代谢转变剂、多维细胞内分子或环境影响剂治疗代谢障碍的方法 |
| EP3120709A1 (en) | 2009-05-28 | 2017-01-25 | IAMS Europe B.V. | Pet food in the form of a coated kibble |
| EP2440212A4 (en) | 2009-06-12 | 2013-03-20 | Generex Pharm Inc | COMPOSITIONS AND METHODS FOR THE PREVENTION AND TREATMENT OF CORONARY DISEASE |
| JP6159084B2 (ja) | 2009-06-30 | 2017-07-05 | デルマン バイオメディシン カンパニー リミテッド | 酒さまたは赤面に関連する皮膚疾患を治療するための、ベルベリンまたはその類似体を含有する組成物 |
| WO2011060305A1 (en) | 2009-11-12 | 2011-05-19 | Nox Technologies, Inc. | Potato skin compositions that lower cytosolic nadh level to mimic calorie restriction |
| WO2012114204A2 (en) | 2011-02-15 | 2012-08-30 | Ecole Polytechnique Federale De Lausanne (Epfl) Epfl-Tto | Methods of treating mitochondrial dysfunction |
| JP2014511890A (ja) | 2011-04-18 | 2014-05-19 | ネステク ソシエテ アノニム | α−ＨＩＣＡ及びα−ケトグルタル酸を含有する栄養組成物 |
| WO2012174537A2 (en) | 2011-06-16 | 2012-12-20 | President And Fellows Of Harvard College | Small molecule screening for mouse satellite cell proliferation |
| CN102586347B (zh) * | 2012-03-06 | 2014-04-09 | 江南大学 | 一种两阶段pH控制高产a-酮戊二酸的方法 |
| US9532997B2 (en) | 2012-04-03 | 2017-01-03 | Whitehead Institute For Biomedical Research | Compositions and methods for promoting intestinal stem cell function |
| ITBO20120226A1 (it) | 2012-04-24 | 2013-10-25 | Alfa Wassermann Spa | Composizioni comprendenti ornitina alfa-chetoglutarato, processi per il loro ottenimento e il loro uso. |
| JP6029058B2 (ja) | 2012-09-14 | 2016-11-24 | 国立研究開発法人農業・食品産業技術総合研究機構 | シュウ酸カルシウムを含む氷核活性剤 |
| CA2884592C (en) | 2012-09-19 | 2021-08-31 | Grespo Ab | Compositions for improvement of brain function |
| CA2896646A1 (en) | 2012-12-27 | 2014-07-03 | Hayashibara Co., Ltd. | Skin-exterior anti-ageing composition and production method therefor |
| US20150328176A1 (en) | 2013-01-25 | 2015-11-19 | Winning The Fight Inc. | Composition for treatment of neurodegenerative disease |
| US9511057B2 (en) | 2013-03-15 | 2016-12-06 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for treating denervation-induced muscle atrophy |
| KR102499654B1 (ko) | 2013-03-19 | 2023-02-13 | 유니버시티 오브 사우스 플로리다 | 상승되고 지속되는 케톤증을 생성하기 위한 조성물 및 방법 |
| US20160263092A1 (en) | 2013-12-19 | 2016-09-15 | Twi Biotechnology, Inc. | Therapeutic uses of berberine formulations |
| KR20160111529A (ko) | 2014-02-12 | 2016-09-26 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 노화 및 연령 관련 질환 및 증상의 치료를 위한 조성물 및 방법 |
| WO2015171723A1 (en) | 2014-05-06 | 2015-11-12 | Research Development Foundation | Methods for treating insulin resistance and for sensitizing patients to glp1 agonist therapy |
| CN106659701B (zh) | 2014-06-30 | 2021-04-27 | 加尼福尼亚大学董事会 | 用于治疗年龄相关性症状和疾病的酮基丁酸酯化合物和组合物 |
| IL282156B (en) | 2014-07-29 | 2022-07-01 | Shenzhen Hightide Biopharmaceutical Ltd | Berberine salts, ursodeoxycholic salts and combinations, methods of preparation and application thereof |
| WO2016019224A1 (en) | 2014-07-31 | 2016-02-04 | Indiana University Research And Technology Corporation | Antithetical regulation of endothelial ace and ace2 by brg1-foxm1 complex underlies pathological cardiac hypertrophy |
| CN104529755B (zh) * | 2014-12-29 | 2016-01-06 | 精晶药业股份有限公司 | 一种从转化液中分离α-酮戊二酸的方法 |
| SG11201708030XA (en) | 2015-04-06 | 2017-10-30 | Shenzhen Hightide Biopharmaceutical Ltd | Conjugate compounds of ursodeoxycholic, berberine or l-carnitine, and compositions and methods thereof |
| JP2018517774A (ja) | 2015-06-10 | 2018-07-05 | エリジウム・ヘルス・インコーポレイテッド | ニコチンアミドリボシドおよびプテロスチルベン組成物ならびに皮膚障害の処置のための方法 |
| US20180193458A1 (en) | 2015-07-08 | 2018-07-12 | Unity Biotechnology, Inc. | Compositions and methods for treating senescence-associated diseases and disorders |
| EP3518915A4 (en) | 2016-09-30 | 2020-04-15 | The Regents of the University of California | ALPHA KETOBUTYRATE, ALPHA KETOGLUTARATE AND 2-HYDROXYBUTYRATE FOR STIMULATING HAIR GROWTH |
| PL231635B1 (pl) | 2017-01-03 | 2019-03-29 | Politechnika Poznanska | Sposób produkcji kwasu alfa-ketoglutarowego (AKG) z jednoskładnikowych roztworów wodnych |
| MX2017004010A (es) | 2017-03-27 | 2018-02-09 | Antonio Hernandez Miramontes Jorge | Mezcla de oxalacetato, alfacetoglutarato, ácido tartánico y sales de lactato de calcio y sodio, para tratar pacientes con insuficiencia renal crónica. |
| SG10202107237SA (en) | 2017-04-25 | 2021-08-30 | Buck Inst Res Aging | Formulations for extending lifespan and healthspan |
| US20200253907A1 (en) | 2017-08-21 | 2020-08-13 | The Regents Of The University Of California | Compositions and Methods for Treating Neurodegenerative Diseases |
| KR102833111B1 (ko) | 2018-09-25 | 2025-07-10 | 폰세 드 리온 헬스 데지그네이티드 액티비티 컴퍼니 | 칼슘 알파-케토글루타레이트의 제조 방법 |
| WO2020086733A1 (en) | 2018-10-24 | 2020-04-30 | Ponce De Leon Health Designated Activity Company | Nicotinamide riboside compositions for healthspan extension |
| US20220265586A1 (en) * | 2019-06-10 | 2022-08-25 | Ponce De Leon Health Designated Activity Company | Sustained-release compositions of alpha-ketoglutarate |
| CN114126599A (zh) | 2019-06-10 | 2022-03-01 | 巴克老龄化研究所 | 改变衰老相关分泌表型的方法和组合物 |
| CA3188646A1 (en) | 2020-07-02 | 2022-01-06 | Ponce De Leon Health Designated Activity Company | Compositions and methods for treating crp-mediated diseases |
| CN112941116B (zh) * | 2021-01-04 | 2022-12-02 | 上海朴颐化学科技有限公司 | 一种酶法制备α-酮戊二酸钙的方法 |
| CN115974679A (zh) * | 2022-12-20 | 2023-04-18 | 绍兴市精益生物化工有限公司 | α-酮戊二酸钙盐制备方法 |
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Patent Citations (1)
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| PH12021550403A1 (en) | 2021-10-04 |
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| CN112955139A (zh) | 2021-06-11 |
| KR102833111B1 (ko) | 2025-07-10 |
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