FI120585B - Stabiili kiteinen (6S)- ja (6R)-tetrahydrofoolihappo - Google Patents

Stabiili kiteinen (6S)- ja (6R)-tetrahydrofoolihappo Download PDF

Info

Publication number: FI120585B
Authority: FI; Finland
Prior art keywords: tetrahydrofolic acid; crystalline; acid; crystallization; water
Prior art date: 1994-05-09

Application number

FI952198A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI952198L (fi

FI952198A0 (fi

Inventor

Hans Rudolf Mueller

Martin Ulmann

Rudolf Moser

Thomas Ammann

Original Assignee

Eprova Ag

Priority date (The priority date 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 date listed.)

1994-05-09

Filing date

1995-05-08

Publication date

2009-12-15

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=4210562&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=FI120585(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1995-05-08 Application filed by Eprova Ag filed Critical Eprova Ag

1995-05-08 Publication of FI952198A0 publication Critical patent/FI952198A0/fi

1995-11-10 Publication of FI952198L publication Critical patent/FI952198L/fi

2009-12-15 Application granted granted Critical

2009-12-15 Publication of FI120585B publication Critical patent/FI120585B/fi

Links

MSTNYGQPCMXVAQ-NEPJUHHUSA-N 6R-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-NEPJUHHUSA-N 0.000 title claims abstract description 64
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 title claims abstract description 58
238000002425 crystallisation Methods 0.000 claims description 48
230000008025 crystallization Effects 0.000 claims description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
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 26
238000000034 method Methods 0.000 claims description 20
238000002360 preparation method Methods 0.000 claims description 14
239000003814 drug Substances 0.000 claims description 7
229940079593 drug Drugs 0.000 claims description 6
239000012452 mother liquor Substances 0.000 claims description 5
239000000725 suspension Substances 0.000 claims description 4
239000004615 ingredient Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
239000000203 mixture Substances 0.000 claims description 3
239000000825 pharmaceutical preparation Substances 0.000 claims description 3
238000001640 fractional crystallisation Methods 0.000 claims description 2
239000003960 organic solvent Substances 0.000 claims description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
239000000126 substance Substances 0.000 description 20
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
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 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
229910021529 ammonia Inorganic materials 0.000 description 9
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 6
235000019152 folic acid Nutrition 0.000 description 6
239000011724 folic acid Substances 0.000 description 6
229960000304 folic acid Drugs 0.000 description 6
239000000047 product Substances 0.000 description 6
239000002253 acid Substances 0.000 description 5
238000001228 spectrum Methods 0.000 description 5
239000000463 material Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-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
238000010586 diagram Methods 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 3
230000000977 initiatory effect Effects 0.000 description 3
239000000843 powder Substances 0.000 description 3
238000011085 pressure filtration Methods 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
239000000729 antidote Substances 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
235000013339 cereals Nutrition 0.000 description 2
239000013078 crystal Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000004052 folic acid antagonist Substances 0.000 description 2
229960002989 glutamic acid Drugs 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
230000003287 optical effect Effects 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
125000001747 pteroyl group Chemical group [H]C1=C([H])C(C(=O)[*])=C([H])C([H])=C1N([H])C([H])([H])C1=C([H])N=C2N([H])C(N([H])[H])=NC(=O)C2=N1 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000005460 tetrahydrofolate Substances 0.000 description 2
SGUBKELXCDHQHX-FXMYHANSSA-N (2s)-2-[[4-[[(6s)-2-amino-4-oxo-5,6,7,8-tetrahydro-1h-pteridin-6-yl]methylamino]benzoyl]amino]pentanedioic acid;sulfuric acid Chemical compound OS(O)(=O)=O.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 SGUBKELXCDHQHX-FXMYHANSSA-N 0.000 description 1
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 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
WZRJTRPJURQBRM-UHFFFAOYSA-N 4-amino-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1.COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 WZRJTRPJURQBRM-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
VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 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
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
229960003896 aminopterin Drugs 0.000 description 1
208000007502 anemia Diseases 0.000 description 1
230000003432 anti-folate effect Effects 0.000 description 1
229940127074 antifolate Drugs 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
229940047766 co-trimoxazole Drugs 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
238000012869 ethanol precipitation Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
235000008191 folinic acid Nutrition 0.000 description 1
239000011672 folinic acid Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229960001691 leucovorin Drugs 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
230000003071 parasitic effect Effects 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000013112 stability test Methods 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
238000000967 suction filtration Methods 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- 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
- 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
- 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
- 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
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- 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
- A61P7/06—Antianaemics

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Hematology (AREA)
Rheumatology (AREA)
Diabetes (AREA)
Obesity (AREA)
Toxicology (AREA)
Pain & Pain Management (AREA)
Transplantation (AREA)
Nutrition Science (AREA)
Tropical Medicine & Parasitology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

FI952198A 1994-05-09 1995-05-08 Stabiili kiteinen (6S)- ja (6R)-tetrahydrofoolihappo FI120585B (fi)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
CH144294		1994-05-09
CH144294A CH686369A5 (de)	1994-05-09	1994-05-09	Stabile kristalline (6S)- und (6R)-Tetrahydrofolseure.

Publications (3)

Publication Number	Publication Date
FI952198A0 FI952198A0 (fi)	1995-05-08
FI952198L FI952198L (fi)	1995-11-10
FI120585B true FI120585B (fi)	2009-12-15

Family

ID=4210562

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI952198A FI120585B (fi)	1994-05-09	1995-05-08	Stabiili kiteinen (6S)- ja (6R)-tetrahydrofoolihappo

Country Status (19)

Country	Link
US (2)	US6271374B1 (fr)
EP (1)	EP0682026B2 (fr)
JP (2)	JP3419585B2 (fr)
KR (1)	KR950032192A (fr)
CN (1)	CN1063444C (fr)
AT (1)	ATE188699T1 (fr)
AU (1)	AU704363B2 (fr)
CA (1)	CA2148671C (fr)
CH (1)	CH686369A5 (fr)
DE (1)	DE59507591D1 (fr)
DK (1)	DK0682026T4 (fr)
ES (1)	ES2144066T5 (fr)
FI (1)	FI120585B (fr)
GR (1)	GR3032984T3 (fr)
HU (1)	HUT71612A (fr)
NO (1)	NO313673B1 (fr)
PT (1)	PT682026E (fr)
RU (1)	RU2165422C2 (fr)
ZA (1)	ZA953673B (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH689831A5 (de) *	1995-11-07	1999-12-15	Eprova Ag	Stabile kristalline Tetrahydrofolsaeure-Salze.
CH693905A5 (de)	1999-04-15	2004-04-15	Eprova Ag	Stabile kristalline Salze von 5-Methyltetrahydrofolsäure.
CH695217A5 (de) *	1999-07-14	2006-01-31	Merck Eprova Ag	Verfahren zur Trennung optischer Isomeren von Tetrahydrofolsäureestersalzen und Tetrahydrofolsäure.
CH694251A5 (de)	1999-07-14	2004-10-15	Eprova Ag	Herstellung von Tetrahydropterin und Derivaten.
ITMI20020132A1 (it)	2002-01-25	2003-07-25	Gmt Fine Chemicals Sa	Processo per l'ottenimento dell'acido (6s)-5,6,7,8-tetraidrofolico
KR20070005550A (ko)	2003-11-17	2007-01-10	바이오마린 파머수티컬 인크.	대사 장애 치료를 위한 조성물 및 방법
KR20060051135A (ko) *	2004-09-15	2006-05-19	니프로 가부시키가이샤	안정화된 주사용 수용액 제재
CA2588994A1 (fr) *	2004-12-08	2006-06-15	Biomarin Pharmaceutical Inc.	Methodes et compositions de traitement de l'hypertension pulmonaire du nouveau-ne
BR112012000614B1 (pt)	2009-07-10	2022-05-24	Linzy O. Scott Iii	Usos de folato no tratamento de hipotireoidismo e composições farmacêuticas compreendendo folato
US8372451B2 (en) *	2010-02-12	2013-02-12	Alexander Vuckovic, M.D., Llc	Compositions and methods for treating depression
JP5925381B2 (ja) *	2012-04-13	2016-05-25	▲連雲▼港金康和信▲薬業▼有限公司ＬｉａｎｙｕｎｇａｎｇＪｉｎｋａｎｇＨｅｘｉｎＰｈａｒｍａｃｅｕｔｉｃａｌＣｏ．，Ｌｔｄ．	化合物［４−（２−アミノ−１０−メチル−４−オキソ−６，７，８，９−テトラヒドロ−４ａ，７−エピミノピリミド［４，５−ｂ］［１，４］ジアゼピン−５（４Ｈ）−イル）ベンゾイル］−グルタメート及びその製造
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
WO2016185413A1 (fr)	2015-05-20	2016-11-24	Nestec S.A.	Formulations à libération modifiée
US10059710B2 (en)	2016-02-17	2018-08-28	Merck & Cie	Stable formulations of 5,10-methylene-(6R)-tetrahydrofolic acid
AU2017397463B2 (en)	2016-11-03	2022-01-06	HedoniaUSA, Inc.	Compositions and methods for treating depression
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1994
- 1994-05-09 CH CH144294A patent/CH686369A5/de not_active IP Right Cessation
1995
- 1995-04-27 DK DK95106285T patent/DK0682026T4/da active
- 1995-04-27 EP EP95106285A patent/EP0682026B2/fr not_active Expired - Lifetime
- 1995-04-27 DE DE59507591T patent/DE59507591D1/de not_active Expired - Lifetime
- 1995-04-27 ES ES95106285T patent/ES2144066T5/es not_active Expired - Lifetime
- 1995-04-27 PT PT95106285T patent/PT682026E/pt unknown
- 1995-04-27 AT AT95106285T patent/ATE188699T1/de active
- 1995-05-02 JP JP10888195A patent/JP3419585B2/ja not_active Expired - Fee Related
- 1995-05-04 CA CA002148671A patent/CA2148671C/fr not_active Expired - Lifetime
- 1995-05-05 RU RU95107144/04A patent/RU2165422C2/ru active
- 1995-05-08 CN CN95106005A patent/CN1063444C/zh not_active Expired - Lifetime
- 1995-05-08 HU HU9501348A patent/HUT71612A/hu unknown
- 1995-05-08 NO NO19951796A patent/NO313673B1/no not_active IP Right Cessation
- 1995-05-08 FI FI952198A patent/FI120585B/fi not_active IP Right Cessation
- 1995-05-08 ZA ZA953673A patent/ZA953673B/xx unknown
- 1995-05-08 AU AU17931/95A patent/AU704363B2/en not_active Ceased
- 1995-05-09 KR KR1019950011214A patent/KR950032192A/ko not_active Ceased
1998
- 1998-01-26 US US09/013,266 patent/US6271374B1/en not_active Expired - Lifetime
2000
- 2000-03-16 GR GR20000400684T patent/GR3032984T3/el not_active IP Right Cessation
2001
- 2001-01-08 US US09/755,072 patent/US6596721B2/en not_active Expired - Fee Related
2003
- 2003-01-28 JP JP2003019261A patent/JP4898081B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
KR950032192A (ko)	1995-12-20
EP0682026B1 (fr)	2000-01-12
CA2148671C (fr)	2000-08-15
JP3419585B2 (ja)	2003-06-23
ES2144066T3 (es)	2000-06-01
JP2003201291A (ja)	2003-07-18
JPH0841062A (ja)	1996-02-13
CH686369A5 (de)	1996-03-15
NO951796L (no)	1995-11-10
NO951796D0 (no)	1995-05-08
JP4898081B2 (ja)	2012-03-14
HUT71612A (en)	1996-01-29
DK0682026T3 (da)	2000-04-17
ATE188699T1 (de)	2000-01-15
CN1122337A (zh)	1996-05-15
ES2144066T5 (es)	2003-11-01
DK0682026T4 (da)	2003-02-24
CN1063444C (zh)	2001-03-21
EP0682026A1 (fr)	1995-11-15
FI952198L (fi)	1995-11-10
NO313673B1 (no)	2002-11-11
DE59507591D1 (de)	2000-02-17
US20010002398A1 (en)	2001-05-31
GR3032984T3 (en)	2000-07-31
AU704363B2 (en)	1999-04-22
CA2148671A1 (fr)	1995-11-10
RU95107144A (ru)	1997-03-20
US6596721B2 (en)	2003-07-22
AU1793195A (en)	1995-11-16
ZA953673B (en)	1996-01-12
PT682026E (pt)	2000-05-31
FI952198A0 (fi)	1995-05-08
US6271374B1 (en)	2001-08-07
RU2165422C2 (ru)	2001-04-20
EP0682026B2 (fr)	2003-02-05

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