IL109639A - High dose pharmaceutical formulations and manufacturing methods therefor - Google Patents

High dose pharmaceutical formulations and manufacturing methods therefor

Info

Publication number: IL109639A
Authority: IL; Israel
Prior art keywords: mycophenolate mofetil; active agent; temperature; pharmaceutical formulation; liquefied
Prior art date: 1993-05-13

Application number

IL109639A

Other languages

English (en)

Other versions

IL109639A0 (en

Inventor

Glenn Jay Samuels

Jung-Chung Lee

Charles Lee

Stephen Berry

Paul Joseph Jarosz

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.)

1993-05-13

Filing date

1994-05-12

Publication date

1998-02-08

1994-05-12 Application filed by Syntex Inc filed Critical Syntex Inc

1994-08-26 Publication of IL109639A0 publication Critical patent/IL109639A0/xx

1998-02-08 Publication of IL109639A publication Critical patent/IL109639A/en

Links

238000004519 manufacturing process Methods 0.000 title claims abstract description 14
239000008194 pharmaceutical composition Substances 0.000 title claims description 21
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 claims abstract description 71
229960004866 mycophenolate mofetil Drugs 0.000 claims abstract description 71
239000000203 mixture Substances 0.000 claims abstract description 40
238000009472 formulation Methods 0.000 claims abstract description 37
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 claims abstract description 28
238000011049 filling Methods 0.000 claims abstract description 23
239000007788 liquid Substances 0.000 claims abstract description 17
239000002552 dosage form Substances 0.000 claims abstract description 15
229960000951 mycophenolic acid Drugs 0.000 claims abstract description 14
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 claims abstract description 14
239000002775 capsule Substances 0.000 claims description 41
239000013543 active substance Substances 0.000 claims description 35
238000002844 melting Methods 0.000 claims description 29
230000008018 melting Effects 0.000 claims description 27
238000000034 method Methods 0.000 claims description 26
239000007903 gelatin capsule Substances 0.000 claims description 25
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical group [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 23
229920002785 Croscarmellose sodium Polymers 0.000 claims description 22
229960001681 croscarmellose sodium Drugs 0.000 claims description 22
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 22
238000001816 cooling Methods 0.000 claims description 15
XKLMZUWKNUAPSZ-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 XKLMZUWKNUAPSZ-UHFFFAOYSA-N 0.000 claims description 13
239000000463 material Substances 0.000 claims description 12
229960000213 ranolazine Drugs 0.000 claims description 12
238000010438 heat treatment Methods 0.000 claims description 11
239000007884 disintegrant Substances 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 8
239000013078 crystal Substances 0.000 claims description 6
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
239000000600 sorbitol Substances 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 2
239000012943 hotmelt Substances 0.000 abstract description 4
239000008203 oral pharmaceutical composition Substances 0.000 abstract 1
150000001875 compounds Chemical class 0.000 description 9
229940079593 drug Drugs 0.000 description 9
239000003814 drug Substances 0.000 description 9
239000007787 solid Substances 0.000 description 5
238000004781 supercooling Methods 0.000 description 5
238000012360 testing method Methods 0.000 description 5
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 4
229960001680 ibuprofen Drugs 0.000 description 4
238000002156 mixing Methods 0.000 description 4
-1 morpholinoethyl ester Chemical class 0.000 description 4
239000007901 soft capsule Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000004480 active ingredient Substances 0.000 description 3
229920002678 cellulose Polymers 0.000 description 3
239000001913 cellulose Substances 0.000 description 3
239000007902 hard capsule Substances 0.000 description 3
PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
239000012768 molten material Substances 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
238000000576 coating method Methods 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
230000006911 nucleation Effects 0.000 description 2
238000010899 nucleation Methods 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
238000007711 solidification Methods 0.000 description 2
230000008023 solidification Effects 0.000 description 2
239000000243 solution Substances 0.000 description 2
229940032147 starch Drugs 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000000126 substance Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
230000009974 thixotropic effect Effects 0.000 description 2
238000011269 treatment regimen Methods 0.000 description 2
GNXFOGHNGIVQEH-UHFFFAOYSA-N 2-hydroxy-3-(2-methoxyphenoxy)propyl carbamate Chemical compound COC1=CC=CC=C1OCC(O)COC(N)=O GNXFOGHNGIVQEH-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
235000006491 Acacia senegal Nutrition 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
241000228143 Penicillium Species 0.000 description 1
201000001068 Prinzmetal angina Diseases 0.000 description 1
206010063837 Reperfusion injury Diseases 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
229930006000 Sucrose Natural products 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
230000006978 adaptation Effects 0.000 description 1
230000006793 arrhythmia Effects 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
229960000830 captopril Drugs 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000012864 cross contamination Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000000428 dust Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000000855 fermentation Methods 0.000 description 1
230000004151 fermentation Effects 0.000 description 1
238000005429 filling process Methods 0.000 description 1
229960002390 flurbiprofen Drugs 0.000 description 1
SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
229960002074 flutamide Drugs 0.000 description 1
238000012395 formulation development Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229960003627 gemfibrozil Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
229960002146 guaifenesin Drugs 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
230000001146 hypoxic effect Effects 0.000 description 1
229960003444 immunosuppressant agent Drugs 0.000 description 1
230000001861 immunosuppressant effect Effects 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
238000001746 injection moulding Methods 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
239000008101 lactose Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000002483 medication Methods 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
229960002330 methocarbamol Drugs 0.000 description 1
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 1
208000010125 myocardial infarction Diseases 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
229960004270 nabumetone Drugs 0.000 description 1
239000011049 pearl Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000003672 processing method Methods 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000006104 solid solution Substances 0.000 description 1
238000005507 spraying Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000011282 treatment Methods 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
235000010447 xylitol 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4833—Encapsulating processes; Filling of capsules
- 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)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Immunology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Transplantation (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

IL109639A 1993-05-13 1994-05-12 High dose pharmaceutical formulations and manufacturing methods therefor IL109639A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US08/061,656 US5455045A (en)	1993-05-13	1993-05-13	High dose formulations

Publications (2)

Publication Number	Publication Date
IL109639A0 IL109639A0 (en)	1994-08-26
IL109639A true IL109639A (en)	1998-02-08

Family

ID=22037233

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL109639A IL109639A (en)	1993-05-13	1994-05-12	High dose pharmaceutical formulations and manufacturing methods therefor

Country Status (23)

Country	Link
US (3)	US5455045A (de)
EP (1)	EP0697866B1 (de)
JP (1)	JP3584037B2 (de)
KR (1)	KR100296214B1 (de)
CN (1)	CN1045884C (de)
AT (1)	ATE187067T1 (de)
AU (1)	AU674960B2 (de)
BR (2)	BR9406604A (de)
CZ (1)	CZ285297B6 (de)
DE (1)	DE69421918T2 (de)
DK (1)	DK0697866T3 (de)
ES (1)	ES2138661T3 (de)
FI (1)	FI114286B (de)
GR (1)	GR3032021T3 (de)
HU (2)	HU226470B1 (de)
IL (1)	IL109639A (de)
NO (1)	NO308828B1 (de)
NZ (1)	NZ266683A (de)
PL (1)	PL175583B1 (de)
PT (1)	PT697866E (de)
RU (1)	RU2135182C1 (de)
TW (1)	TW434010B (de)
WO (1)	WO1994026266A1 (de)

Families Citing this family (55)

* Cited by examiner, † Cited by third party
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ATE113471T1 (de) *	1989-08-17	1994-11-15	Cortecs Ltd	Arzneiformulierungen.
US5455045A (en) *	1993-05-13	1995-10-03	Syntex (U.S.A.) Inc.	High dose formulations
WO1996031197A1 (en) *	1995-04-03	1996-10-10	Abbott Laboratories	Homogeneous mixtures of low temperature-melting drugs and additives for controlled release
ID18663A (id)	1996-04-12	1998-04-30	Novartis Ag	Komposisi farmasi berlapis enterik
UA72207C2 (uk) *	1998-04-07	2005-02-15	Брістол- Майєрс Сквібб Фарма Компані	Фармацевтична композиція ефавіренцу з добавкою дезінтегруючих агентів у вигляді швидкорозчинних капсул або таблеток та спосіб її виготовлення
US6303607B1 (en) *	1998-09-10	2001-10-16	Cv Therapeutics, Inc.	Method for administering a sustained release ranolanolazine formulation
US6479496B1 (en) *	1998-09-10	2002-11-12	Cv Therapeutics, Inc.	Methods for treating angina with ranolazine
EP1259230A2 (de)	2000-02-18	2002-11-27	Cv Therapeutics, Inc.	Partielle inhibitoren der fettsäureoxidation zur behandlung des kongestiven herzversagens
US6451798B2 (en)	2000-02-22	2002-09-17	Cv Therapeutics, Inc.	Substituted alkyl piperazine derivatives
US6677336B2 (en)	2000-02-22	2004-01-13	Cv Therapeutics, Inc.	Substituted piperazine compounds
US6552023B2 (en)	2000-02-22	2003-04-22	Cv Therapeutics, Inc.	Aralkyl substituted piperazine compounds
WO2001062749A1 (en)	2000-02-22	2001-08-30	Cv Therapeutics, Inc.	Substituted piperazine compounds
AU2001239827A1 (en)	2000-02-22	2001-09-03	Cv Therapeutics, Inc.	Substituted alkylene diamine compounds
US6573264B1 (en)	2000-10-23	2003-06-03	Cv Therapeutics, Inc.	Heteroaryl alkyl piperazine derivatives
GB0124953D0 (en) *	2001-10-17	2001-12-05	Novartis Ag	Organic Compounds
CN100551370C (zh) *	2002-05-21	2009-10-21	Cv医药有限公司	雷诺嗪在制备治疗糖尿病的药物组合物中的应用
US8822473B2 (en) *	2002-05-21	2014-09-02	Gilead Sciences, Inc.	Method of treating diabetes
ES2287574T3 (es) *	2002-12-05	2007-12-16	Cv Therapeutics, Inc.	Compuestos de piperacina sustituidos y su utilizacion como inhibidores de la oxidacion de acidos grasos.
KR20050086956A (ko) *	2003-01-03	2005-08-30	씨브이 쎄러퓨틱스, 인코포레이티드	치환된 복소환 화합물
AU2004209522A1 (en) *	2003-01-17	2004-08-19	Gilead Palo Alto, Inc.	Substituted heterocyclic compounds useful in the treatment of cardiovascular diseases
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
EP1644345A1 (de) *	2003-06-23	2006-04-12	Cv Therapeutics, Inc.	Harnstoff-derivate von piperazinen und piperidinen als fettsäureoxidations-inhibitoren
KR20060124646A (ko)	2003-12-18	2006-12-05	씨브이 쎄러퓨틱스, 인코포레이티드	1-아칸-2-올 치환된 피페라진 및 피페리딘 화합물
US7683188B2 (en) *	2004-04-26	2010-03-23	TEVA Gyógyszergyár Zártkōrūen Mūkōdō Részvénytársaság	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.
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1993
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1994
- 1994-04-25 TW TW083103771A patent/TW434010B/zh not_active IP Right Cessation
- 1994-05-09 US US08/239,621 patent/US5472707A/en not_active Expired - Lifetime
- 1994-05-10 PT PT94916722T patent/PT697866E/pt unknown
- 1994-05-10 AU AU68301/94A patent/AU674960B2/en not_active Expired
- 1994-05-10 WO PCT/US1994/005196 patent/WO1994026266A1/en not_active Ceased
- 1994-05-10 CZ CZ952954A patent/CZ285297B6/cs not_active IP Right Cessation
- 1994-05-10 RU RU95122420A patent/RU2135182C1/ru active
- 1994-05-10 JP JP52565394A patent/JP3584037B2/ja not_active Expired - Lifetime
- 1994-05-10 DE DE69421918T patent/DE69421918T2/de not_active Expired - Lifetime
- 1994-05-10 DK DK94916722T patent/DK0697866T3/da active
- 1994-05-10 EP EP94916722A patent/EP0697866B1/de not_active Expired - Lifetime
- 1994-05-10 HU HU9503224A patent/HU226470B1/hu unknown
- 1994-05-10 NZ NZ266683A patent/NZ266683A/en not_active IP Right Cessation
- 1994-05-10 CN CN94192045A patent/CN1045884C/zh not_active Expired - Lifetime
- 1994-05-10 AT AT94916722T patent/ATE187067T1/de active
- 1994-05-10 PL PL94311654A patent/PL175583B1/pl unknown
- 1994-05-10 BR BR9406604A patent/BR9406604A/pt not_active Application Discontinuation
- 1994-05-10 KR KR1019950704984A patent/KR100296214B1/ko not_active Expired - Lifetime
- 1994-05-10 ES ES94916722T patent/ES2138661T3/es not_active Expired - Lifetime
- 1994-05-12 IL IL109639A patent/IL109639A/en not_active IP Right Cessation
1995
- 1995-04-24 HU HU95P/P00110P patent/HU211270A9/hu unknown
- 1995-06-02 US US08/459,227 patent/US5554384A/en not_active Expired - Lifetime
- 1995-11-10 FI FI955439A patent/FI114286B/fi not_active IP Right Cessation
- 1995-11-10 NO NO954546A patent/NO308828B1/no not_active IP Right Cessation
1997
- 1997-05-09 BR BR1100723-0A patent/BR1100723A/pt active IP Right Grant
1999
- 1999-12-02 GR GR990401633T patent/GR3032021T3/el unknown

Also Published As

Publication number	Publication date
US5554384A (en)	1996-09-10
US5472707A (en)	1995-12-05
IL109639A0 (en)	1994-08-26
JP3584037B2 (ja)	2004-11-04
RU2135182C1 (ru)	1999-08-27
HUT72978A (en)	1996-06-28
AU6830194A (en)	1994-12-12
BR1100723A (pt)	2000-04-18
NO308828B1 (no)	2000-11-06
DK0697866T3 (da)	2000-04-17
NO954546L (no)	1995-11-10
HU211270A9 (en)	1995-11-28
WO1994026266A1 (en)	1994-11-24
FI955439L (fi)	1995-11-10
CN1122571A (zh)	1996-05-15
BR9406604A (pt)	1996-01-02
CZ285297B6 (cs)	1999-06-16
TW434010B (en)	2001-05-16
PL175583B1 (pl)	1999-01-29
PL311654A1 (en)	1996-03-04
ATE187067T1 (de)	1999-12-15
PT697866E (pt)	2000-04-28
EP0697866B1 (de)	1999-12-01
EP0697866A1 (de)	1996-02-28
KR960702304A (ko)	1996-04-27
KR100296214B1 (ko)	2001-10-24
JPH08510254A (ja)	1996-10-29
HU226470B1 (en)	2008-12-29
GR3032021T3 (en)	2000-03-31
FI955439A0 (fi)	1995-11-10
CZ295495A3 (en)	1996-02-14
NZ266683A (en)	1996-08-27
AU674960B2 (en)	1997-01-16
US5455045A (en)	1995-10-03
DE69421918T2 (de)	2000-03-30
CN1045884C (zh)	1999-10-27
ES2138661T3 (es)	2000-01-16
HU9503224D0 (en)	1996-01-29
NO954546D0 (no)	1995-11-10
DE69421918D1 (de)	2000-01-05
FI114286B (fi)	2004-09-30

Legal Events

Date	Code	Title
1998-07-15	FF	Patent granted
1998-12-06	KB	Patent renewed
2000-08-31	KB	Patent renewed
2004-06-20	KB	Patent renewed
2008-08-10	KB	Patent renewed
2012-05-31	KB	Patent renewed
2014-12-31	EXP	Patent expired

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