CN1277197A - 5-甲基四氢叶酸的稳定晶体盐 - Google Patents
5-甲基四氢叶酸的稳定晶体盐 Download PDFInfo
- Publication number
- CN1277197A CN1277197A CN00108884A CN00108884A CN1277197A CN 1277197 A CN1277197 A CN 1277197A CN 00108884 A CN00108884 A CN 00108884A CN 00108884 A CN00108884 A CN 00108884A CN 1277197 A CN1277197 A CN 1277197A
- Authority
- CN
- China
- Prior art keywords
- methyl
- tetrahydrofolic acid
- thfa
- salt
- water
- 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.)
- Granted
Links
- 150000003839 salts Chemical class 0.000 title claims abstract description 32
- 239000013078 crystal Substances 0.000 title claims description 25
- ZNOVTXRBGFNYRX-ABLWVSNPSA-N levomefolic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-ABLWVSNPSA-N 0.000 title description 32
- 229940105150 5-methyltetrahydrofolic acid Drugs 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 6
- MSTNYGQPCMXVAQ-KIYNQFGBSA-N 5,6,7,8-tetrahydrofolic acid Chemical compound N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-KIYNQFGBSA-N 0.000 claims description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 238000002425 crystallisation Methods 0.000 claims description 32
- 230000008025 crystallization Effects 0.000 claims description 32
- 159000000007 calcium salts Chemical class 0.000 claims description 25
- ZNOVTXRBGFNYRX-STQMWFEESA-N (6S)-5-methyltetrahydrofolic acid Chemical compound C([C@@H]1N(C=2C(=O)N=C(N)NC=2NC1)C)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-STQMWFEESA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 9
- 239000000725 suspension Substances 0.000 claims description 9
- 238000007669 thermal treatment Methods 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000000470 constituent Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000002778 food additive Substances 0.000 abstract 1
- 235000013373 food additive Nutrition 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 235000007635 levomefolic acid Nutrition 0.000 description 23
- 239000011578 levomefolic acid Substances 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000001291 vacuum drying Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000003643 water by type Substances 0.000 description 6
- ZNOVTXRBGFNYRX-OLZOCXBDSA-N (2s)-2-[[4-[[(6r)-2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl]methylamino]benzoyl]amino]pentanedioic acid Chemical compound C([C@H]1N(C=2C(=O)NC(N)=NC=2NC1)C)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-OLZOCXBDSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000005755 formation reaction Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000005169 Debye-Scherrer Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QHFQAJHNDKBRBO-UHFFFAOYSA-L calcium chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ca+2] QHFQAJHNDKBRBO-UHFFFAOYSA-L 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- -1 5-methyl tetrahydrofolate salt Chemical class 0.000 description 2
- NRGONRDRXCPMIC-GDKBPFBDSA-N N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CC(C=O)C(O)=O)C(O)=O)C=C1 Chemical compound N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CC(C=O)C(O)=O)C(O)=O)C=C1 NRGONRDRXCPMIC-GDKBPFBDSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000001914 filtration Methods 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
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 239000005460 tetrahydrofolate Substances 0.000 description 2
- LPJXPACOXRZCCP-VIFPVBQESA-N (2s)-2-benzamidopentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)C1=CC=CC=C1 LPJXPACOXRZCCP-VIFPVBQESA-N 0.000 description 1
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002065 Anaemia megaloblastic Diseases 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- JRSHMRFEWSBYLO-UHFFFAOYSA-N C[C-]1NC=CC1=O Chemical compound C[C-]1NC=CC1=O JRSHMRFEWSBYLO-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 208000000682 Megaloblastic Anemia Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 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
- 206010028980 Neoplasm Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000003432 anti-folate effect Effects 0.000 description 1
- 229940127074 antifolate Drugs 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 229940125687 antiparasitic agent Drugs 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical class O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100001016 megaloblastic anemia Toxicity 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 201000010193 neural tube defect Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 150000003195 pteridines Chemical class 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 229940061969 rheumatrex Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960005404 sulfamethoxazole Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
- 229960001082 trimethoprim Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
Abstract
Description
贮存月数 | ||||||
0 | 3 | 6 | 12 | 18 | 88 | |
5-甲基-(6S)-四氢叶酸结晶钙盐 | 100% | 98.6% | 98.7% | 99.1% | 99.0% | 97.8% |
5-甲基-(6S)-四氢叶酸无定型钙盐 | 100% | 84.2% |
晶型 | 选定的2θ值 |
I型II型III型IV型 | 6.5,13.3,16.8和20.15.3,6.9,8.7和21.16.8,10.2,15.4和22.56.6,15.9,20.2和22.5 |
晶型 | 在20℃下的溶解度 | |
0.9%NaCl | 水 | |
I型II型III型 | 1.6%5.8%1.5% | 1.1%3.8%1.0% |
Claims (15)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH00695/99A CH693905A5 (de) | 1999-04-15 | 1999-04-15 | Stabile kristalline Salze von 5-Methyltetrahydrofolsäure. |
CH695/1999 | 1999-04-15 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1277197A true CN1277197A (zh) | 2000-12-20 |
CN1154648C CN1154648C (zh) | 2004-06-23 |
Family
ID=4193016
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB00108884XA Expired - Lifetime CN1154648C (zh) | 1999-04-15 | 2000-04-14 | 5-甲基四氢叶酸的稳定晶体钙盐及其制备方法和用途 |
Country Status (19)
Country | Link |
---|---|
US (1) | US6441168B1 (zh) |
EP (5) | EP1695975A1 (zh) |
JP (4) | JP5202774B2 (zh) |
KR (2) | KR100774012B1 (zh) |
CN (1) | CN1154648C (zh) |
AT (2) | ATE451372T1 (zh) |
AU (1) | AU782641B2 (zh) |
CA (1) | CA2305926C (zh) |
CH (1) | CH693905A5 (zh) |
CY (2) | CY1109874T1 (zh) |
DE (2) | DE50016064D1 (zh) |
DK (4) | DK1044975T3 (zh) |
ES (3) | ES2336190T3 (zh) |
HU (1) | HU229423B1 (zh) |
NO (1) | NO325495B1 (zh) |
PT (4) | PT1044975E (zh) |
RU (1) | RU2265605C2 (zh) |
TW (1) | TWI285205B (zh) |
ZA (1) | ZA200001851B (zh) |
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102516247A (zh) * | 2010-12-15 | 2012-06-27 | 连云港金康医药科技有限公司 | A型l-5-甲基四氢叶酸钙盐多晶型及其制备方法 |
CN102584826A (zh) * | 2012-01-20 | 2012-07-18 | 连云港金康医药科技有限公司 | (6s)-5-甲基四氢叶酸盐晶型及其制备方法 |
CN102702200A (zh) * | 2012-04-25 | 2012-10-03 | 连云港金康和信药业有限公司 | (6rs)-5-甲基四氢叶酸钙盐晶型及其制备方法 |
CN102775407A (zh) * | 2012-01-20 | 2012-11-14 | 连云港金康医药科技有限公司 | 稳定的5-甲基四氢叶酸晶型及其制备方法 |
CN102813663A (zh) * | 2006-07-06 | 2012-12-12 | 拜耳医药股份有限公司 | 包含四氢叶酸的药物组合物 |
WO2013107236A1 (zh) * | 2012-01-20 | 2013-07-25 | 连云港金康和信药业有限公司 | (6s)-5-甲基四氢叶酸盐晶型及其制备方法 |
WO2013163917A1 (zh) * | 2012-04-13 | 2013-11-07 | 连云港金康和信药业有限公司 | 化合物jk12a及其制备 |
CN103450202A (zh) * | 2012-06-04 | 2013-12-18 | 南京莱因医药科技有限公司 | L-5-甲基四氢叶酸与有机碱加成盐的方法 |
CN103664945A (zh) * | 2012-09-07 | 2014-03-26 | 南京莱因医药科技有限公司 | L-5-甲基四氢叶酸氨基酸盐的制备方法 |
CN103694239A (zh) * | 2012-09-27 | 2014-04-02 | 上海科胜药物研发有限公司 | 一种5-甲基-(6s)-四氢叶酸晶型a及其制备方法 |
CN103980279A (zh) * | 2014-04-16 | 2014-08-13 | 悦康药业集团有限公司 | 一种甲氨蝶呤化合物及注射用甲氨蝶呤 |
CN107304212A (zh) * | 2016-04-21 | 2017-10-31 | 常州爱诺新睿医药技术有限公司 | 一种无定型l-5-甲基四氢叶酸氨基酸盐及其制备方法 |
CN107698591A (zh) * | 2015-09-25 | 2018-02-16 | 上海华理生物医药有限公司 | (6s)-5-甲基四氢叶酸锌盐晶型及其制备方法 |
CN110461844A (zh) * | 2017-03-31 | 2019-11-15 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸与有机碱的结晶二元钠盐 |
CN110461845A (zh) * | 2017-03-31 | 2019-11-15 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸的结晶钠盐 |
CN110475778A (zh) * | 2017-03-31 | 2019-11-19 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸的结晶钠盐 |
CN112334470A (zh) * | 2018-07-06 | 2021-02-05 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸和氨基酸乙酯的结晶盐 |
CN112368269A (zh) * | 2018-07-06 | 2021-02-12 | 默克专利股份有限公司 | 包含5-甲基-(6s)-四氢叶酸和4-(2-羟乙基)-吗啉的结晶盐 |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH693905A5 (de) * | 1999-04-15 | 2004-04-15 | Eprova Ag | Stabile kristalline Salze von 5-Methyltetrahydrofolsäure. |
US20020094970A1 (en) * | 2000-12-14 | 2002-07-18 | Ronenn Roubenoff | Compositions and methods for treating an arthritic condition |
HUE029533T2 (en) | 2003-11-17 | 2017-03-28 | Biomarin Pharm Inc | Treatment of phenylketonuria with BH4 |
ATE498401T1 (de) * | 2004-09-15 | 2011-03-15 | Nipro Corp | Wässrige, stabile (6s)-folinsäurelösung zur injektion |
US20100130500A1 (en) * | 2004-12-08 | 2010-05-27 | Biomarin Pharmaceutical Inc. | Methods and compositions for the treatment of pulmonary hypertension of the newborn |
UY29527A1 (es) | 2005-05-13 | 2006-12-29 | Schering Ag | Composicinn farmaccutica que contienen gestrgenos y/o estrngenos y 5-metil - (6s) - tetrhidrofolato. |
KR20090029824A (ko) * | 2006-07-06 | 2009-03-23 | 바이엘 쉐링 파마 악티엔게젤샤프트 | 피임용 및 선천성 기형 위험 예방용 제약 제제 |
EP1891959A1 (de) * | 2006-08-14 | 2008-02-27 | Bayer Schering Pharma Aktiengesellschaft | Pharmazeutische Zusammensetzung zur Kontrazeption und zur Verminderung des Risikos angeborener Fehlbildungen |
US8617597B2 (en) | 2006-07-06 | 2013-12-31 | Bayer Intellectual Property Gmbh | Pharmaceutical composition containing a tetrahydrofolic acid |
CH698729B1 (de) | 2007-05-30 | 2009-10-15 | Cerbios Pharma Sa | Stabile, kristalline (6S)-N(5)-Methyl-5, 6,7,8-tetrahydrofolsäure. |
EP2027855A1 (de) | 2007-08-24 | 2009-02-25 | Bayer Schering Pharma AG | Verwendung von Gestagenen in Kombination mit (6S)5-Methyltetrahydrofolat zur Therapie der Endometriose mit gleichzeitiger Verminderung von Therapie-Nebenwirkungen sowie der Verminderung des Risikos angeborener Fehlbildungen bei Eintritt einer Gravidität |
US20090060997A1 (en) * | 2007-08-27 | 2009-03-05 | Christian Seitz | Process for producing a pharmaceutical preparation for therapeutic treatment of endometriosis containing a combination of a gestagen and (6s)-5-methyltetrahydrofolate |
WO2009101021A2 (en) * | 2008-02-13 | 2009-08-20 | Bayer Schering Pharma Aktiengesellschaft | Estradiol-containing drug delivery system |
KR20100117603A (ko) * | 2008-02-13 | 2010-11-03 | 바이엘 쉐링 파마 악티엔게젤샤프트 | 안정화 효과를 갖는 약물 전달 시스템 |
SI2245032T1 (sl) * | 2008-02-20 | 2015-08-31 | Gnosis S.P.A., | Folati, sestavki in njihove uporabe |
CA3031481C (en) * | 2009-07-10 | 2021-03-16 | Linzy O. Scott, Iii | Methods and compositions for treating thyroid-related medical conditions with reduced folates |
UY32836A (es) | 2009-08-12 | 2011-03-31 | Bayer Schering Pharma Ag | Partículas estabilizadas que comprenden 5-metil-(6s)-tetrahidrofolato |
CA2825428C (en) | 2010-02-12 | 2022-06-14 | Alexander Vuckovic, M.D., Llc | Compositions and methods for treating depression |
JP5785622B2 (ja) * | 2010-12-03 | 2015-09-30 | コチャク ファルマ イラチュ ヴェキミャ サン.アー.シェーKocak Farma Ilac Ve Kimya San.A.S | その構造内にグルタミン酸部分を有する葉酸拮抗薬の新規な製造方法 |
EP2502625A1 (en) | 2011-03-21 | 2012-09-26 | GMT Fine Chemicals SA | Process for the preparation of crystalline levofolinic acid |
EP2781214A1 (en) * | 2013-03-22 | 2014-09-24 | Chemo Research, S.L. | Formulation of amorphous calcium L-5-methyltetrahydrofolate (L-5-MTHF-Ca) |
JP2016525576A (ja) * | 2013-07-29 | 2016-08-25 | アデア ファーマシューティカルズ,インコーポレイテッド | 安定化された修飾放出型葉酸誘導体組成物、その治療用途および製造方法 |
US20160053281A1 (en) | 2013-08-15 | 2016-02-25 | The University Court Of The University Of Edinburgh | Enhanced Expression Of RNA Vectors |
US9629846B1 (en) | 2013-11-14 | 2017-04-25 | Argent Development Group, Llc | Nutritional supplements for women desiring to become pregnant, and pregnant and nursing women |
US9492421B1 (en) | 2013-11-14 | 2016-11-15 | Argent Development Group, Llc | Nutritional supplements for treatment of iron deficiency anemia |
EP2878600B1 (en) | 2013-12-02 | 2018-06-27 | Cerbios-Pharma S.A. | Stable complexes of an alkaline earth metal salt of N5-methyl-tetrahydrofolic acid and a polyol |
WO2015193778A1 (en) | 2014-06-16 | 2015-12-23 | Mylan Laboratories Ltd. | Crystalline form of levomefolate calcium |
KR20170047394A (ko) | 2014-09-04 | 2017-05-04 | 리안윤강 진강 해신 파머수티컬 코. 엘티디. | (6s)-5-메틸테트라히드로폴산 또는 그 염의 조성물 및 그 제조와 용도 |
CN107812195B (zh) * | 2014-09-04 | 2021-04-20 | 连云港金康和信药业有限公司 | (6s)‐5‐甲基‐四氢叶酸钙盐的稳定药物组合物 |
CN107812197B (zh) | 2014-09-20 | 2018-09-18 | 中国药科大学 | 一种炎症靶向的中性粒细胞递药系统及其应用 |
WO2016135707A1 (en) | 2015-02-27 | 2016-09-01 | Nestec S.A. | Diagnosis of major depressive disorder, mild cognitive impairment, and alzheimer's disease and other neurologic and psychiatric disorders |
WO2016185413A1 (en) | 2015-05-20 | 2016-11-24 | Nestec S.A. | Modified release formulations |
DE202015105351U1 (de) | 2015-10-09 | 2016-01-07 | Apotheke am Schlossplatz Inh. Mario Ganster e.K. | Diätetische Zusammensetzung |
KR101712807B1 (ko) | 2015-10-19 | 2017-03-07 | 오인숙 | 스테인레스 빔 제조장치 |
CN105237539A (zh) * | 2015-10-29 | 2016-01-13 | 上海应用技术学院 | A晶型(6s)-5-甲基四氢叶酸锌盐及其制备方法 |
AU2017397463B2 (en) | 2016-11-03 | 2022-01-06 | HedoniaUSA, Inc. | Compositions and methods for treating depression |
EP3461826A1 (en) | 2017-09-29 | 2019-04-03 | Aprofol AG | Multifunctional folate salts |
PT3817812T (pt) * | 2018-07-06 | 2023-12-28 | Merck Patent Gmbh | Sal cristalino de acido 5-metil-(68)-tetra-hidrofólico e éster etílico de l-isoleucina |
US20210275533A1 (en) | 2018-07-06 | 2021-09-09 | Merck Patent Gmbh | Crystalline salts of 5-methyl-(6S)-tetrahydrofolic acid and L-valine ethyl ester |
CA3105545A1 (en) | 2018-07-06 | 2020-01-09 | Merck Patent Gmbh | Crystalline salts of 5-methyl-(6s)-tetrahydrofolic acid and l-leucine ethyl ester |
EP3646873A1 (en) | 2018-10-31 | 2020-05-06 | Aprofol AG | Folate salts |
EP3666260A1 (en) | 2018-12-13 | 2020-06-17 | Laboratorios Leon Farma SA | Ethinyl estradiol-beta-cyclodextrin complex and process for preparing thereof |
JPWO2021215494A1 (zh) | 2020-04-23 | 2021-10-28 | ||
CA3172190A1 (en) | 2020-05-15 | 2021-11-18 | Alfasigma S.P.A. | Composition comprising methylfolate |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1572137A (en) * | 1977-02-22 | 1980-07-23 | Bioresearch Sas Del Dr Livio C | Stable compositions for therapeutic use based on d,1-5-methyltetrahydrofolic acid and its salts |
US5223500A (en) * | 1977-02-22 | 1993-06-29 | Bioresearch S.P.A. | Stable pharmaceutical composition of alkaline or alkaline earth 5-methyl tetrahydrofolate |
DE3821875C1 (zh) * | 1988-06-29 | 1990-02-15 | Eprova Ag, Forschungsinstitut, Schaffhausen, Ch | |
CH680731A5 (zh) * | 1990-04-12 | 1992-10-30 | Sapec Fine Chemicals | |
CH681303A5 (zh) | 1991-01-16 | 1993-02-26 | Eprova Ag | |
CH684270A5 (de) | 1991-10-04 | 1994-08-15 | Sapec Fine Chemicals | Verfahren zur Herstellung von Erdalkalimetallsalzen von (6R)-N(10)-Formyl-5,6,7,8-tetrahydrofolsäure. |
CH683261A5 (it) * | 1991-10-10 | 1994-02-15 | Applied Pharma Res | Procedimento per la preparazione dell'acido metiltetraidrofolico nella forma (6(R,S)(-))N-5 e separazione del diastereoisomero attivo (6(S)(-))N-5) sotto forma di sali. |
CH682664A5 (en) | 1991-10-15 | 1993-10-29 | Eprova Ag | Stable salts of 5,10-methylene tetrahydrofolate. |
CH682665A5 (de) * | 1991-10-29 | 1993-10-29 | Sapec Fine Chemicals | Verfahren zur Reinigung von rohen Erdalkalimetallsalzen von N(5)-Methyl-5,6,7,8-tetrahydrofolsäure. |
DE4136921A1 (de) * | 1991-11-11 | 1993-05-13 | Knoll Ag | Verfahren zur trennung von 5-methyl-tetrahydrofolsaeure |
CH686672A5 (de) * | 1992-12-01 | 1996-05-31 | Cerbios Pharma Sa | Verfahren zur Herstellung von (6S)-5,6,7,8-Tetrahydrofolsaeure. |
CH686369A5 (de) * | 1994-05-09 | 1996-03-15 | Eprova Ag | Stabile kristalline (6S)- und (6R)-Tetrahydrofolseure. |
CH689831A5 (de) * | 1995-11-07 | 1999-12-15 | Eprova Ag | Stabile kristalline Tetrahydrofolsaeure-Salze. |
PT877563E (pt) | 1996-01-31 | 2004-08-31 | Univ South Alabama | Preparacoes alimentares e vitaminicas contendo o isomero natural de folatos reduzidos |
CH693905A5 (de) * | 1999-04-15 | 2004-04-15 | Eprova Ag | Stabile kristalline Salze von 5-Methyltetrahydrofolsäure. |
-
1999
- 1999-04-15 CH CH00695/99A patent/CH693905A5/de not_active IP Right Cessation
-
2000
- 2000-04-08 EP EP06010738A patent/EP1695975A1/de not_active Withdrawn
- 2000-04-08 DE DE50016064T patent/DE50016064D1/de not_active Expired - Lifetime
- 2000-04-08 EP EP09178427A patent/EP2194057B1/de not_active Expired - Lifetime
- 2000-04-08 AT AT00107623T patent/ATE451372T1/de active
- 2000-04-08 AT AT09178426T patent/ATE496052T1/de active
- 2000-04-08 PT PT00107623T patent/PT1044975E/pt unknown
- 2000-04-08 DK DK00107623.1T patent/DK1044975T3/da active
- 2000-04-08 PT PT09178428T patent/PT2192120E/pt unknown
- 2000-04-08 DK DK09178428.0T patent/DK2192120T3/da active
- 2000-04-08 EP EP00107623A patent/EP1044975B1/de not_active Expired - Lifetime
- 2000-04-08 EP EP09178428A patent/EP2192120B1/de not_active Expired - Lifetime
- 2000-04-08 ES ES00107623T patent/ES2336190T3/es not_active Expired - Lifetime
- 2000-04-08 ES ES09178427T patent/ES2374369T3/es not_active Expired - Lifetime
- 2000-04-08 DE DE50015815T patent/DE50015815D1/de not_active Expired - Lifetime
- 2000-04-08 PT PT09178427T patent/PT2194057E/pt unknown
- 2000-04-08 EP EP09178426A patent/EP2189459B1/de not_active Expired - Lifetime
- 2000-04-08 ES ES09178428T patent/ES2374371T3/es not_active Expired - Lifetime
- 2000-04-08 DK DK09178427.2T patent/DK2194057T3/da active
- 2000-04-08 PT PT09178426T patent/PT2189459E/pt unknown
- 2000-04-08 DK DK09178426.4T patent/DK2189459T3/da active
- 2000-04-12 AU AU27689/00A patent/AU782641B2/en not_active Expired
- 2000-04-12 ZA ZA200001851A patent/ZA200001851B/xx unknown
- 2000-04-12 TW TW089106827A patent/TWI285205B/zh not_active IP Right Cessation
- 2000-04-12 NO NO20001886A patent/NO325495B1/no not_active IP Right Cessation
- 2000-04-13 JP JP2000112606A patent/JP5202774B2/ja not_active Expired - Lifetime
- 2000-04-13 CA CA002305926A patent/CA2305926C/en not_active Expired - Lifetime
- 2000-04-14 CN CNB00108884XA patent/CN1154648C/zh not_active Expired - Lifetime
- 2000-04-14 KR KR1020000019508A patent/KR100774012B1/ko not_active IP Right Cessation
- 2000-04-14 HU HU0001560A patent/HU229423B1/hu unknown
- 2000-04-14 RU RU2000109346/04A patent/RU2265605C2/ru active
- 2000-04-17 US US09/551,405 patent/US6441168B1/en not_active Expired - Lifetime
-
2007
- 2007-05-30 KR KR1020070052657A patent/KR100874368B1/ko active IP Right Grant
-
2010
- 2010-03-04 CY CY20101100212T patent/CY1109874T1/el unknown
-
2011
- 2011-03-03 CY CY20111100250T patent/CY1111313T1/el unknown
-
2012
- 2012-12-03 JP JP2012264085A patent/JP5675759B2/ja not_active Expired - Lifetime
- 2012-12-03 JP JP2012264084A patent/JP5675758B2/ja not_active Expired - Lifetime
- 2012-12-03 JP JP2012264086A patent/JP5675760B2/ja not_active Expired - Lifetime
Cited By (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102813663A (zh) * | 2006-07-06 | 2012-12-12 | 拜耳医药股份有限公司 | 包含四氢叶酸的药物组合物 |
CN102813663B (zh) * | 2006-07-06 | 2019-03-22 | 拜耳知识产权有限责任公司 | 包含四氢叶酸的药物组合物 |
CN102516247A (zh) * | 2010-12-15 | 2012-06-27 | 连云港金康医药科技有限公司 | A型l-5-甲基四氢叶酸钙盐多晶型及其制备方法 |
CN102775407B (zh) * | 2012-01-20 | 2015-08-05 | 连云港金康医药科技有限公司 | 稳定的无定型5-甲基四氢叶酸盐及其制备方法 |
US9150982B2 (en) | 2012-01-20 | 2015-10-06 | Lianyungang Jinkang Hexin Pharmaceutical Co. Ltd. | Crystal form of (6S)-5-methyltetrahydrofolate salt and method for preparing same |
CN102584826A (zh) * | 2012-01-20 | 2012-07-18 | 连云港金康医药科技有限公司 | (6s)-5-甲基四氢叶酸盐晶型及其制备方法 |
CN102775407A (zh) * | 2012-01-20 | 2012-11-14 | 连云港金康医药科技有限公司 | 稳定的5-甲基四氢叶酸晶型及其制备方法 |
WO2013107236A1 (zh) * | 2012-01-20 | 2013-07-25 | 连云港金康和信药业有限公司 | (6s)-5-甲基四氢叶酸盐晶型及其制备方法 |
CN102584826B (zh) * | 2012-01-20 | 2015-04-29 | 连云港金康医药科技有限公司 | (6s)-5-甲基四氢叶酸盐晶型及其制备方法 |
US9090623B2 (en) | 2012-04-13 | 2015-07-28 | Lianyungang Jinkang Hexin Pharmaceutical Co., Ltd. | Compound JK12A and preparation thereof |
WO2013163917A1 (zh) * | 2012-04-13 | 2013-11-07 | 连云港金康和信药业有限公司 | 化合物jk12a及其制备 |
CN104334561A (zh) * | 2012-04-13 | 2015-02-04 | 连云港金康和信药业有限公司 | 化合物jk12a及其制备 |
CN104334561B (zh) * | 2012-04-13 | 2016-06-22 | 连云港金康和信药业有限公司 | 化合物jk12a及其制备 |
CN102702200A (zh) * | 2012-04-25 | 2012-10-03 | 连云港金康和信药业有限公司 | (6rs)-5-甲基四氢叶酸钙盐晶型及其制备方法 |
CN102702200B (zh) * | 2012-04-25 | 2014-11-12 | 连云港金康和信药业有限公司 | (6rs)-5-甲基四氢叶酸钙盐晶型及其制备方法 |
CN103450202A (zh) * | 2012-06-04 | 2013-12-18 | 南京莱因医药科技有限公司 | L-5-甲基四氢叶酸与有机碱加成盐的方法 |
CN103450202B (zh) * | 2012-06-04 | 2015-07-01 | 南京莱因医药科技有限公司 | L-5-甲基四氢叶酸与有机碱加成盐的方法 |
CN103664945A (zh) * | 2012-09-07 | 2014-03-26 | 南京莱因医药科技有限公司 | L-5-甲基四氢叶酸氨基酸盐的制备方法 |
CN103664945B (zh) * | 2012-09-07 | 2016-01-20 | 南京莱因医药科技有限公司 | L-5-甲基四氢叶酸氨基酸盐的制备方法 |
CN103694239B (zh) * | 2012-09-27 | 2016-12-21 | 上海科胜药物研发有限公司 | 一种5‑甲基‑(6s)‑四氢叶酸晶型a及其制备方法 |
CN103694239A (zh) * | 2012-09-27 | 2014-04-02 | 上海科胜药物研发有限公司 | 一种5-甲基-(6s)-四氢叶酸晶型a及其制备方法 |
CN103980279B (zh) * | 2014-04-16 | 2016-07-06 | 悦康药业集团有限公司 | 一种甲氨蝶呤化合物及注射用甲氨蝶呤 |
CN103980279A (zh) * | 2014-04-16 | 2014-08-13 | 悦康药业集团有限公司 | 一种甲氨蝶呤化合物及注射用甲氨蝶呤 |
CN107698591A (zh) * | 2015-09-25 | 2018-02-16 | 上海华理生物医药有限公司 | (6s)-5-甲基四氢叶酸锌盐晶型及其制备方法 |
CN107304212A (zh) * | 2016-04-21 | 2017-10-31 | 常州爱诺新睿医药技术有限公司 | 一种无定型l-5-甲基四氢叶酸氨基酸盐及其制备方法 |
CN110461844A (zh) * | 2017-03-31 | 2019-11-15 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸与有机碱的结晶二元钠盐 |
CN110461845A (zh) * | 2017-03-31 | 2019-11-15 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸的结晶钠盐 |
CN110475778A (zh) * | 2017-03-31 | 2019-11-19 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸的结晶钠盐 |
CN110461845B (zh) * | 2017-03-31 | 2023-05-12 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸的结晶钠盐 |
CN110461844B (zh) * | 2017-03-31 | 2024-03-12 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸与有机碱的结晶二元钠盐 |
CN112334470A (zh) * | 2018-07-06 | 2021-02-05 | 默克专利股份有限公司 | 5-甲基-(6s)-四氢叶酸和氨基酸乙酯的结晶盐 |
CN112368269A (zh) * | 2018-07-06 | 2021-02-12 | 默克专利股份有限公司 | 包含5-甲基-(6s)-四氢叶酸和4-(2-羟乙基)-吗啉的结晶盐 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1277197A (zh) | 5-甲基四氢叶酸的稳定晶体盐 | |
JP4898081B2 (ja) | 安定な結晶性(6s)−テトラヒドロ葉酸 | |
CN1067392C (zh) | 稳定结晶的四氢叶酸盐 | |
US9150982B2 (en) | Crystal form of (6S)-5-methyltetrahydrofolate salt and method for preparing same | |
US8633202B2 (en) | Crystalline levofolinic acid and process for its preparation | |
US20210220366A1 (en) | Crystalline salt comprising 5-methyl-(6s)-tetrahydrofolic acid and 4-(2-hydroxyethyl)-morpholine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: MERCK + CIE PARTNERSHIP CORPORATION Free format text: FORMER OWNER: EPROVA AG (CH) FORSCHUNGSINSTITUT IM LATERNENACKER 5 CH-8200 SCHAFFHAUSEN (SWITZ Effective date: 20110511 |
|
C41 | Transfer of patent application or patent right or utility model | ||
C56 | Change in the name or address of the patentee |
Owner name: MERCK + CIE CORPORATION Free format text: FORMER NAME: MERCK + CIE PARTNERSHIP CORPORATION |
|
CP01 | Change in the name or title of a patent holder |
Address after: Schaffhausen, Switzerland Patentee after: Eprova AG Address before: Schaffhausen, Switzerland Patentee before: Merck and Seay partnership |
|
TR01 | Transfer of patent right |
Effective date of registration: 20110511 Address after: Schaffhausen, Switzerland Patentee after: Merck and Seay partnership Address before: Schaffhausen, Switzerland Patentee before: Eprova AG |
|
CX01 | Expiry of patent term |
Granted publication date: 20040623 |
|
CX01 | Expiry of patent term |