IL110970A - Crystalline anhydrous mycophenolate mofetil pharmaceutical composition containing it and its preparation - Google Patents

Crystalline anhydrous mycophenolate mofetil pharmaceutical composition containing it and its preparation

Info

Publication number: IL110970A
Authority: IL; Israel
Prior art keywords: compound; crystalline anhydrous; salt; range; temperature
Prior art date: 1993-09-15

Application number

IL11097094A

Other languages

English (en)

Other versions

IL110970A0 (en

Original Assignee

Syntex Inc

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.)

1993-09-15

Filing date

1994-09-14

Publication date

1999-01-26

1994-09-14 Application filed by Syntex Inc filed Critical Syntex Inc

1994-11-28 Publication of IL110970A0 publication Critical patent/IL110970A0/xx

1999-01-26 Publication of IL110970A publication Critical patent/IL110970A/en

Links

229960004866 mycophenolate mofetil Drugs 0.000 title description 17
RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 title description 17
238000002360 preparation method Methods 0.000 title description 14
239000008194 pharmaceutical composition Substances 0.000 title description 9
239000000203 mixture Substances 0.000 claims abstract description 76
238000009472 formulation Methods 0.000 claims abstract description 39
150000001875 compounds Chemical class 0.000 claims abstract description 33
238000001990 intravenous administration Methods 0.000 claims abstract description 27
150000003839 salts Chemical class 0.000 claims abstract description 26
150000001450 anions Chemical class 0.000 claims abstract description 14
229910019142 PO4 Inorganic materials 0.000 claims abstract description 13
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims abstract description 13
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 13
239000010452 phosphate Substances 0.000 claims abstract description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims abstract description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 42
238000000034 method Methods 0.000 claims description 31
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 20
230000003247 decreasing effect Effects 0.000 claims description 20
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 17
229920000053 polysorbate 80 Polymers 0.000 claims description 17
230000008569 process Effects 0.000 claims description 15
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 14
229940068968 polysorbate 80 Drugs 0.000 claims description 14
201000010099 disease Diseases 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
208000023275 Autoimmune disease Diseases 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
239000000546 pharmaceutical excipient Substances 0.000 claims description 10
239000007788 liquid Substances 0.000 claims description 8
238000013329 compounding Methods 0.000 claims description 7
238000002844 melting Methods 0.000 claims description 5
230000008018 melting Effects 0.000 claims description 5
238000000634 powder X-ray diffraction Methods 0.000 claims description 5
206010028980 Neoplasm Diseases 0.000 claims description 4
201000004681 Psoriasis Diseases 0.000 claims description 4
230000000747 cardiac effect Effects 0.000 claims description 4
206010012601 diabetes mellitus Diseases 0.000 claims description 4
238000000113 differential scanning calorimetry Methods 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
238000011068 loading method Methods 0.000 claims description 3
238000001757 thermogravimetry curve Methods 0.000 claims description 2
230000003612 virological effect Effects 0.000 claims description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 abstract description 3
239000000243 solution Substances 0.000 description 49
229910000041 hydrogen chloride Inorganic materials 0.000 description 34
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 34
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
238000004108 freeze drying Methods 0.000 description 26
HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 23
HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 21
-1 morpholinoethyl ester Chemical class 0.000 description 19
229960000951 mycophenolic acid Drugs 0.000 description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000008215 water for injection Substances 0.000 description 14
239000004615 ingredient Substances 0.000 description 12
150000004682 monohydrates Chemical group 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
150000002148 esters Chemical class 0.000 description 8
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
241000124008 Mammalia Species 0.000 description 7
OWLCGJBUTJXNOF-HDNKIUSMSA-N hydron;2-morpholin-4-ylethyl (e)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1h-2-benzofuran-5-yl)-4-methylhex-4-enoate;chloride Chemical compound Cl.COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 OWLCGJBUTJXNOF-HDNKIUSMSA-N 0.000 description 7
229940087560 mycophenolate mofetil hydrochloride Drugs 0.000 description 7
238000002424 x-ray crystallography Methods 0.000 description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
238000001938 differential scanning calorimetry curve Methods 0.000 description 6
235000019441 ethanol Nutrition 0.000 description 6
235000013350 formula milk Nutrition 0.000 description 6
239000000463 material Substances 0.000 description 6
238000002441 X-ray diffraction Methods 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
239000002253 acid Substances 0.000 description 4
239000006172 buffering agent Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
241001465754 Metazoa Species 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
239000008395 clarifying agent Substances 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000001802 infusion Methods 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
230000036961 partial effect Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
241000700605 Viruses Species 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000004067 bulking agent Substances 0.000 description 2
230000008859 change Effects 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 2
229940014456 mycophenolate Drugs 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
230000036470 plasma concentration Effects 0.000 description 2
239000007858 starting material Substances 0.000 description 2
WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
HRCMWNGXWRNWPF-ICSBZGNSSA-N Cl.C(C)OC(CC\C(=C\CC=1C(=C2C(OCC2=C(C1OC)C)=O)O)\C)=O Chemical compound Cl.C(C)OC(CC\C(=C\CC=1C(=C2C(OCC2=C(C1OC)C)=O)O)\C)=O HRCMWNGXWRNWPF-ICSBZGNSSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
206010062016 Immunosuppression Diseases 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
RTGDFNSFWBGLEC-UHFFFAOYSA-N Mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1CC=C(C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-UHFFFAOYSA-N 0.000 description 1
241000228143 Penicillium Species 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
230000002411 adverse Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
238000005056 compaction Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000000855 fermentation Methods 0.000 description 1
230000004151 fermentation Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical group O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
238000012792 lyophilization process Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229950007856 mofetil Drugs 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
239000000047 product Substances 0.000 description 1
230000001185 psoriatic effect Effects 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
238000000954 titration curve Methods 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000007704 transition Effects 0.000 description 1
230000035899 viability Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
- 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
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Pain & Pain Management (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Transplantation (AREA)
Virology (AREA)
Rheumatology (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Saccharide Compounds (AREA)
Medicinal Preparation (AREA)
Furan Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)

IL11097094A 1993-09-15 1994-09-14 Crystalline anhydrous mycophenolate mofetil pharmaceutical composition containing it and its preparation IL110970A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US12184193A	1993-09-15	1993-09-15

Publications (2)

Publication Number	Publication Date
IL110970A0 IL110970A0 (en)	1994-11-28
IL110970A true IL110970A (en)	1999-01-26

Family

ID=22399119

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL11097094A IL110970A (en)	1993-09-15	1994-09-14	Crystalline anhydrous mycophenolate mofetil pharmaceutical composition containing it and its preparation

Country Status (31)

Country	Link
US (2)	US5543408A (de)
EP (1)	EP0724581B1 (de)
JP (1)	JP3411038B2 (de)
KR (1)	KR100349772B1 (de)
CN (1)	CN1060770C (de)
AT (1)	ATE173475T1 (de)
AU (1)	AU677435B2 (de)
BR (1)	BR9407469A (de)
CA (1)	CA2171836C (de)
CZ (1)	CZ292423B6 (de)
DE (1)	DE69414720T2 (de)
DK (1)	DK0724581T3 (de)
ES (1)	ES2123831T3 (de)
FI (1)	FI119639B (de)
HU (1)	HU217300B (de)
IL (1)	IL110970A (de)
LT (1)	LT4052B (de)
LV (1)	LV11326B (de)
MX (1)	MXPA94007099A (de)
NO (1)	NO314727B1 (de)
NZ (1)	NZ273801A (de)
PH (1)	PH30685A (de)
PL (1)	PL178522B1 (de)
RO (2)	RO118075B1 (de)
RU (1)	RU2132849C1 (de)
SG (1)	SG55006A1 (de)
SI (1)	SI9420052B (de)
TW (1)	TW370527B (de)
UA (1)	UA49797C2 (de)
WO (1)	WO1995007902A1 (de)
ZA (1)	ZA947088B (de)

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GB9512854D0 (en) *	1995-06-23	1995-08-23	Wellcome Found	Novel formulation
IN188985B (de) *	1998-12-09	2002-11-30	Biocon Ltd
CZ292123B6 (cs) *	2001-06-08	2003-08-13	Ivax Pharmaceuticals S.R.O.	Způsob přípravy mykofenolátu mofetilu
GB0301259D0 (en)	2003-01-20	2003-02-19	Novartis Ag	Organic compounds
GB0307553D0 (en) *	2003-04-01	2003-05-07	Novartis Ag	Organic compounds
US20050187170A1 (en) *	2003-06-16	2005-08-25	Biocryst Pharmaceuticals, Inc.	Enhancing the efficiency of RNA polymerase inhibitors by using inosine monophosphate dehydrogenase inhibitors
DE602004015310D1 (de) *	2003-09-11	2008-09-04	Sandoz Ag	Verfahren zur herstellung von mycophenolatmofetil
WO2005105768A2 (en) *	2004-04-26	2005-11-10	Teva Gyógyszergyár Zàrtköruen Muködo Rèszvènytàrsasàg	Process for preparation of mycophenolic acid and ester derivatives thereof
MXPA06005658A (es) *	2004-04-27	2007-04-10	Teva Gyogyszergyar Zartkoruen	Proceso para preparacion de micofenolato mofetil, y otros esteres de acido micofenolico.
EP1768662A2 (de)	2004-06-24	2007-04-04	Novartis Vaccines and Diagnostics, Inc.	Immunstimulatoren kleiner moleküle und assays für deren nachweis
TWI322147B (en) *	2004-07-20	2010-03-21	Teva Gyogyszergyar Zartkoruen Mukodo Reszvenytarsasag	Crystalline mycophenolate sodium
CN100383520C (zh) *	2004-09-20	2008-04-23	复旦大学	一种测定人血浆中霉酚酸及其代谢物的方法
EP1917010A2 (de) *	2005-02-08	2008-05-07	Aspreva Pharmaceuticals SA	Zusammensetzungen und verfahren zur behandlung von gefäss-, autoimmun- und entzündlichen erkrankungen
WO2006086498A2 (en) *	2005-02-08	2006-08-17	Aspreva Pharmaceuticals Sa	Treatment of vascular, autoimmune and inflammatory diseases using low dosages of impdh inhibitors
US20080281111A1 (en) *	2005-04-26	2008-11-13	Sandor Molnar	Process for preparation of mycophenolate mofetil and other esters of mycophenolic acid
EP2436381A1 (de)	2006-06-27	2012-04-04	Sandoz AG	Kristallisierung von Halogenwasserstoffen von pharmazeutischen Verbindungen
CN101953807A (zh) *	2010-10-09	2011-01-26	山西普德药业有限公司	一种注射用吗替麦考酚酯冻干粉针剂及其制备方法
MX386935B (es)	2013-03-14	2025-03-04	Alkermes Pharma Ireland Ltd	Profármacos de fumaratos y su uso en el tratamiento de diferentes enfermedades.
US8669281B1 (en)	2013-03-14	2014-03-11	Alkermes Pharma Ireland Limited	Prodrugs of fumarates and their use in treating various diseases
US9168246B2 (en)	2013-06-27	2015-10-27	Veloxis Pharmaceutical A/S	Regimen for suppressing organ rejection
JP6337135B2 (ja)	2014-02-24	2018-06-06	アルカーメスファーマアイルランドリミテッド	フマル酸エステルのスルホンアミドプロドラッグ及びスルフィンアミドプロドラッグ並びに種々の疾患の治療におけるその使用
WO2018167628A1 (en)	2017-03-13	2018-09-20	Ftf Pharma Private Limited	Pharmaceutical composition of oral suspension of immunosuppressive agents
GB2591396B (en)	2018-08-18	2023-06-07	Ftf Pharma Private Ltd	Pharmaceutical suspension for oral dosage
CA3212370A1 (en)	2021-03-03	2022-09-09	Sana Biotechnology, Inc.	Immunosuppressive therapies for use with cardiomyocyte cell therapies, and associated methods and compositions

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Publication number	Priority date	Publication date	Assignee	Title
US4328213A (en) *	1979-11-28	1982-05-04	Schering Corporation	Stable injectable labetalol formulation
US4478829A (en) *	1983-04-28	1984-10-23	Armour Pharmaceutical Company	Pharmaceutical preparation containing purified fibronectin
SU1170760A1 (ru) *	1984-02-20	1996-09-20	Ф.Ю. Рачинский	Дигидробромид 2-(2-морфолиноэтилтио)бензимидазола, повышающий физическую работоспособность и ускоряющий процессы восстановления после физических нагрузок и длительного стресса
US4753935A (en)	1987-01-30	1988-06-28	Syntex (U.S.A.) Inc.	Morpholinoethylesters of mycophenolic acid and pharmaceutical compositions
FR2653999A1 (fr) *	1989-11-06	1991-05-10	Adir	Nouveaux derives de la morpholine, leur procede de preparation et les compositions pharmaceutiques les renfermant.

1994
- 1994-09-12 BR BR9407469A patent/BR9407469A/pt not_active Application Discontinuation
- 1994-09-12 ES ES94928054T patent/ES2123831T3/es not_active Expired - Lifetime
- 1994-09-12 WO PCT/US1994/010142 patent/WO1995007902A1/en not_active Ceased
- 1994-09-12 DK DK94928054T patent/DK0724581T3/da active
- 1994-09-12 SI SI9420052A patent/SI9420052B/sl unknown
- 1994-09-12 PL PL94313480A patent/PL178522B1/pl unknown
- 1994-09-12 NZ NZ273801A patent/NZ273801A/en not_active IP Right Cessation
- 1994-09-12 RO RO96-00567A patent/RO118075B1/ro unknown
- 1994-09-12 HU HU9600652A patent/HU217300B/hu unknown
- 1994-09-12 RU RU96107396A patent/RU2132849C1/ru active
- 1994-09-12 CZ CZ1996788A patent/CZ292423B6/cs not_active IP Right Cessation
- 1994-09-12 CA CA002171836A patent/CA2171836C/en not_active Expired - Lifetime
- 1994-09-12 DE DE69414720T patent/DE69414720T2/de not_active Expired - Lifetime
- 1994-09-12 CN CN94193413A patent/CN1060770C/zh not_active Expired - Lifetime
- 1994-09-12 JP JP50925595A patent/JP3411038B2/ja not_active Expired - Lifetime
- 1994-09-12 SG SG1996001679A patent/SG55006A1/en unknown
- 1994-09-12 AT AT94928054T patent/ATE173475T1/de active
- 1994-09-12 EP EP94928054A patent/EP0724581B1/de not_active Expired - Lifetime
- 1994-09-12 RO ROA200201154A patent/RO118427B1/ro unknown
- 1994-09-12 AU AU77238/94A patent/AU677435B2/en not_active Expired
- 1994-09-12 KR KR1019960701354A patent/KR100349772B1/ko not_active Expired - Lifetime
- 1994-09-14 ZA ZA947088A patent/ZA947088B/xx unknown
- 1994-09-14 TW TW083108484A patent/TW370527B/zh not_active IP Right Cessation
- 1994-09-14 PH PH48985A patent/PH30685A/en unknown
- 1994-09-14 IL IL11097094A patent/IL110970A/en not_active IP Right Cessation
- 1994-12-05 US US08/349,236 patent/US5543408A/en not_active Expired - Lifetime
- 1994-12-09 UA UA96031026A patent/UA49797C2/uk unknown
1995
- 1995-06-02 US US08/459,991 patent/US5545637A/en not_active Expired - Lifetime
1996
- 1996-03-13 FI FI961169A patent/FI119639B/fi not_active IP Right Cessation
- 1996-03-15 LV LVP-96-85A patent/LV11326B/en unknown
- 1996-03-15 NO NO19961075A patent/NO314727B1/no not_active IP Right Cessation
- 1996-03-15 LT LT96-028A patent/LT4052B/lt not_active IP Right Cessation
1997
- 1997-12-05 MX MXPA94007099A patent/MXPA94007099A/es active IP Right Grant

Also Published As

Publication number	Publication date
RO118075B1 (ro)	2003-01-30
LT96028A (en)	1996-08-26
HUT75119A (en)	1997-04-28
WO1995007902A1 (en)	1995-03-23
ZA947088B (en)	1996-03-14
PL313480A1 (en)	1996-07-08
CZ78896A3 (en)	1996-10-16
EP0724581B1 (de)	1998-11-18
DK0724581T3 (da)	1999-08-02
NO961075D0 (no)	1996-03-15
UA49797C2 (uk)	2002-10-15
RU2132849C1 (ru)	1999-07-10
RO118427B1 (ro)	2003-05-30
PL178522B1 (pl)	2000-05-31
SI9420052B (sl)	2004-02-29
FI119639B (fi)	2009-01-30
PH30685A (en)	1997-09-16
AU677435B2 (en)	1997-04-24
JPH09502721A (ja)	1997-03-18
LV11326A (lv)	1996-06-20
ES2123831T3 (es)	1999-01-16
FI961169L (fi)	1996-03-13
FI961169A0 (fi)	1996-03-13
CZ292423B6 (cs)	2003-09-17
KR100349772B1 (ko)	2002-12-28
JP3411038B2 (ja)	2003-05-26
HK1012624A1 (en)	1999-08-06
NO961075L (no)	1996-03-15
CA2171836C (en)	2006-11-14
MXPA94007099A (es)	2004-01-23
TW370527B (en)	1999-09-21
DE69414720T2 (de)	1999-04-08
SG55006A1 (en)	1998-12-21
US5543408A (en)	1996-08-06
LT4052B (en)	1996-10-25
HU9600652D0 (en)	1996-05-28
CN1131420A (zh)	1996-09-18
HU217300B (hu)	1999-12-28
AU7723894A (en)	1995-04-03
IL110970A0 (en)	1994-11-28
DE69414720D1 (de)	1998-12-24
BR9407469A (pt)	1996-11-12
EP0724581A1 (de)	1996-08-07
SI9420052A (en)	1996-12-31
CN1060770C (zh)	2001-01-17
ATE173475T1 (de)	1998-12-15
NZ273801A (en)	1997-10-24
NO314727B1 (no)	2003-05-12
US5545637A (en)	1996-08-13
CA2171836A1 (en)	1995-03-23
LV11326B (en)	1996-10-20

Legal Events

Date	Code	Title
1999-07-14	FF	Patent granted
2000-07-26	KB	Patent renewed
2000-08-31	KB	Patent renewed
2001-06-14	KB	Patent renewed
2004-11-10	KB	Patent renewed
2009-02-11	KB	Patent renewed
2010-04-14	KB	Patent renewed
2012-09-24	KB	Patent renewed
2015-04-30	EXP	Patent expired

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