NO314748B1 - Anvendelse av forbindelsen 5-[4-[2-(5-etylpyridin-2-yl)- etoksy]benzyl]tiazolidin-2,4-dion (pioglitazone) for fremstilling av et medikamentfor behandling av svekket glukosetoleranse - Google Patents
Anvendelse av forbindelsen 5-[4-[2-(5-etylpyridin-2-yl)- etoksy]benzyl]tiazolidin-2,4-dion (pioglitazone) for fremstilling av et medikamentfor behandling av svekket glukosetoleranse Download PDFInfo
- Publication number
- NO314748B1 NO314748B1 NO20002963A NO20002963A NO314748B1 NO 314748 B1 NO314748 B1 NO 314748B1 NO 20002963 A NO20002963 A NO 20002963A NO 20002963 A NO20002963 A NO 20002963A NO 314748 B1 NO314748 B1 NO 314748B1
- Authority
- NO
- Norway
- Prior art keywords
- glucose tolerance
- impaired glucose
- preparation
- treatment
- pioglitazone
- Prior art date
Links
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Description
Område for oppfinnelsen
Foreliggende oppfinnelse angår anvendelse av forbindelsen 5-[4-[2-(5-etylpyridin-2-yl)etoksy]benzyl]tiazolidin-2,4-dion (pioglitazone) eller et farmasøytisk akseptabelt salt derav, ved fremstilling av et medikament for behandling av svekket glukosetoleranse for å forhindre eller forsinke starten av ikke-insulinavhengig diabetes mellitus i en pasient som lider av svekket glukosetoleranse.
Bakgrunn
Diabetes er én av de mest fremherskende kroniske syk-dommer over hele verden med signifikante personlige og økonomiske kostnader for pasienter og deres familier, så vel som for sam-funnet. Forskjellige typer av diabetes eksisterer med distinkte etiologier og patogeneser. Eksempelvis er diabetes mellitus en forstyrrelse av karbohydratmetabolismen som er karakterisert ved hyperglykemi og glykosuria og resulterende fra utilstrekkelig produksjon eller utnyttelse av insulin.
Diabetes mellitus utvikles ofte fra visse risikopopu-lasjoner og én slik populasjon er individer med svekket glukosetoleranse (IGT). Svekket glukosetoleranse er en tilstand mellom vanlig ikke-insulinavhengig diabetes mellitus og normal glukosetoleranse, hvori den angrepne persons postprandiale glukose-respons er unormal som vurdert ved 2-timers postprandiale plasma-glukosenivåer. Denne IGT-populasjon utvikles til en bestemt form for diabetes mellitus, spesifikt ikke-insulinavhengig diabetes mellitus (NIDDM).
NIDDM eller for øvrig referert til som diabetes type II, er den form for diabetes mellitus som oppstår i overveiende grad i voksne, hvori tilstrekkelig produksjon av insulin er tilgjengelig for bruk, men likevel eksisterer en mangel i insulin-formidlet utnyttelse og metabolisme av glukose i perifere vev. Det er blitt vist at for enkelte mennesker med diabetes resulterer en genetisk predisposisjon i genet som koder for insulin og/eller insulinreseptoren og/eller insulinformidlet signaltransduksjonsfaktor(er), og derved,resulterende i ineffek-tiv insulin og/eller insulinformidlede effekter og således en svekkelse av utnyttelsen eller metabolismen av glukose. Popula-sjonen med svekket glukosetoleranse utvikles til NIDDM i en grad på 5 % til 10 % av tilfeller pr. år.
En manglende evne til å behandle NIDDM kan resultere i død pga. kardiovaskulær sykdom og i andre diabetiske komplikasjoner innbefattende retinopati, nefropati og perifer neuropati. I mange år har behandling av NIDDM involvert et program med det mål og nedsette blodsukker med en kombinasjon med en diett og mosjon. Alternativt har behandling av NIDDM involvert orale hypoglysemiske midler, slik som sulfonylureaer alene eller i kombinasjon med insulininjeksjoner. Nylig er alfa-glukosidase-inhibitorer, slik som acarbose, blitt vist å være effektive til å redusere den postprandiale stigning i blodglukose (Lefevre et al., Drugs 1992; 44, 29-38). I Europa og Canada er en annen behandling anvendt primært i fete diabetikere metformin, et biguanid.
I alle tilfelle er hva som er nødvendig en metode for å behandle populasjoner som opplever svekket glukosetoleranse for å forhindre eller forsinke starten av NIDDM og derved bringe lind-ring av symptomer, forbedre livskvaliteten, forhindre akutte og langvarige komplikasjoner, redusere dødeligheten og behandle led-sagende forstyrrelser i de med risiko for NIDDM.
Sammendrag av Turner og Clapham i Progress in Drug Research, vol. 51, 1998 (se i særdeleshet s. 60 til 67) viser klart at ytterligere tiazolidindionlegemidler slik som pioglitazon, har glimrende aktivitet når det gjelder å føre pasienter med IGT tilbake til normal glukosetoleranse. Ytterligere bevis med hensyn til virksomheten av pioglitazon ved behandling av individer med IGT er angitt i publikasjonen av Sturis et al. Sammenligning av resultatene med den "tidlige pioglitazon"-gruppe og den "ubehandlede" gruppe viser klart at administrering av pioglitazon før diabetesstart forhindret starten av hyperglykemi (se i særdeleshet diskusjonen angitt på s. E790 og E791). Prediabetiske ZDF-rotter er ekvivalente med individer med IGT.
Sammendrag av oppfinnelsen
Foreliggende oppfinnelse angår som ovenfor nevnt anvendelse av forbindelsen 5-[4-[2-(5-etylpyridin-2-yl)etoksy]-benzyl]tiazolidin-2,4-dion (pioglitazone) eller et farmasøytisk akseptabelt salt derav, ved fremstilling av et medikament for behandling av svekket glukosetoleranse for å forhindre eller forsinke starten av ikke-insulinavhengig diabetes mellitus i en pasient som lider av svekket glukosetoleranse.
Det er kjent at personer med svekket glukosetoleranse har en meget høyere grad av videre utvikling til NIDDM enn personer med normal glukosetoleranse. Saad, et al., New Engl J Med 1988; 319:1500-6. Hvis svekket glukosetoleranse kan normal-iseres, er det sannsynlig at det videre forløp til NIDDM vil bli forsinket eller forhindret i denne populasjon.
Detaljert beskrivelse av foretrukne utførelsesformer
Farmasøytisk akseptable syreaddisjonssalter av forbindelsene innbefatter salter avledet fra ikke-toksiske uorganiske syrer, slik som saltsyre, salpetersyre, fosforsyre, svovelsyre, hydrobromsyre, hydrojodsyre, hydrofluorsyre, fosforsyre og lignende, så vel som salter avledet fra ikke-toksiske, organiske syrer, slik som alifatiske mono- og dikarboksylsyrer, fenylsub-stituerte alkansyrer, hydroksyalkansyrer, alkandisyrer, aromatiske syrer, alifatiske og aromatiske sulfonsyrer etc. Slike salter innbefatter således sulfat, pyrosulfat, bisulfat, sulfitt, bisulfitt, nitrat, fosfat, monohydrogenfosfat, dihydrogenfosfat, metafosfat, pyrofosfat, klorid, bromid, jodid, acetat, trifluor-acetat, propionat, kaprylat, isobutyrat, oksalat, malonat, suksinat, suberat, sebakat, fumarat, maleat, mandelat, benzoat, klorbenzoat, metylbenzoat, dinitrobenzoat, ftalat, benzensul-fonat, toluensulfonat, fenylacetat, sitrat, laktat, maleat, tartrat, metansulfonat og lignende. Også tatt i betraktning er salter av aminosyrer, slik som arginat og lignende og glukonat, galakturonat, n-metylglukamin (se f.eks. Berge S. M., et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science 1977, 66, 1-19).
Syreaddisjonssaltene av angitte basiske forbindelser fremstilles ved å bringe den frie baseform i kontakt med en tilstrekkelig mengde av den ønskede syre for å gi saltet på vanlig måte. Den frie baseform kan regenereres ved å bringe saltformen i kontakt med en base og isolere den frie base på konvensjonell måte eller som ovenfor. De frie baseformer avviker fra deres respektive saltformer noe i visse fysikalske egenskaper, slik som løselighet i polare løsningsmidler, men ellers er saltene ekvivalente med deres respektive frie base for oppfinnelsens formål.
Farmasøytisk akseptable baseaddisjonssalter dannes med metaller eller aminer, slik som alkali og jordalkalimetaller eller organiske aminer. Eksempler på metaller anvendt som kat-ioner, er natrium, kalium, magnesium, kalsium og lignende. Eksempler på egnede aminer er N,N'-dibenzyletylendiamin, klorpro-kain, kolin, dietanolamin, disykloheksylamin, etylendiamin, N-metylglukamin og prokain (se f.eks. Berge S. M., et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science 1977, 66, 1-19) .
Baseaddisjonssaltene av angitte syreforbindelser fremstilles ved å bringe den frie syreform i kontakt med en tilstrekkelig mengde av den ønskede base for å gi saltet på vanlig måte. Den frie syreform kan regenereres ved å bringe saltformen i kontakt med en syre og isolere den frie syre på konvensjonell måte eller som ovenfor. De frie syreformer avviker fra deres respektive saltformer noe i visse fysikalske egenskaper, slik som løselighet i polare løsningsmidler, men ellers er saltene ekvivalente med deres respektive frie syre for oppfinnelsens formål.
For fremstilling av farmasøytiske preparater fra forbindelsen ifølge oppfinnelsen, kan farmasøytisk akseptable bærere være enten faste eller væskeformige. Faste preparatformer innbefatter pulvere, tabletter, piller, kapsler, poser, stikkpiller og dispergerbare granuler. En fast bærer kan være én eller flere substanser som også virker som fortynningsmidler, smaksgivende midler, bindemidler, konserveringsmidler, tablettoppbrytende midler eller et innkapslende materiale.
I pulvere er bæreren et fint oppdelt, fast materiale som er i blanding med den fint oppdelte, aktive komponent.
I tabletter blandes den aktive komponent med bæreren med de nødvendige bindende egenskaper i egnede proporsjoner og presses i den ønskede form og størrelse.
Pulverne og tablettene inneholder fortrinnsvis fra
5 eller 10 til ca. 70 % av den aktive forbindelse. Egnede bærere er magnesiumkarbonat, magnesiumstearat, talkum, sukker, laktose, pektin, dekstrin, stivelse, gelatin, tragant, metylcellulose, natriumkarboksymetylcellulose, et lavtsmeltende voks, kakaosmør og lignende. Uttrykket "preparat" er beregnet på å innbefatte formuleringen av den aktive forbindelse med innkapslende materiale, slik som en bærer som tilveiebringer en kapsel, hvori den aktive komponent, med eller uten andre bærere, er omgitt av en bærer som således er i assosiasjon med denne. På lignende måte er poser og pastiller innbefattet. Tabletter, pulvere, kapsler, pillere, poser og pastiller kan anvendes som faste doserings-former egnet for oral administrering.
For fremstilling av stikkpiller smeltes først et lavtsmeltende voks, slik som en blanding av fettsyreglyserider eller kakaosmør, og den aktive komponent dispergeres homogent deri, slik som ved omrøring. Den smeltede homogene blanding helles deretter over i støpeformer med egnet størrelse, tillates og avkjøles og derved å stivne.
Væskeformige preparater innbefatter løsninger, suspensjoner og emulsjoner, f.eks. vann eller vannpropylenglykol-løsninger. For parenteral injeksjon kan væskeformige preparater formuleres i løsning i vandig polyetylenglykolløsning.
Vandige løsninger egnet for oral bruk, kan fremstilles ved oppløsning av den aktive komponent i vann og tilsetning av egnede fargestoffer, smaksgivende midler, stabiliserings- og fortynningsmidler, som ønsket.
Vandige suspensjoner egnet for oral bruk, kan fremstilles ved dispergering av den finoppdelte, aktive komponent i vann med et viskøst materiale, slik som naturlige eller syntet-iske gummier, harpikser, metylcellulose, natriumkarboksymetylcellulose og andre velkjente suspenderingsmidler.
Også innbefattet er preparater i fast form som er beregnet på å bli omdannet, kort før bruk, til preparater i væskeform for oral administrering. Slike væskeformer innbefatter løsninger, suspensjoner og emulsjoner. Disse preparater kan inneholde i tillegg til den aktive komponent, fargestoffer, smaksmidler, stabilisatorer, buffere, kunstige og naturlige søtningsmidler, dispergeringsmidler, fortykker, oppløselig-gjørende midler og lignende.
Det farmasøytiske preparat er fortrinnsvis i enhets-doseringsform. I en slik form oppdeles preparatet i enhetsdoser inneholdende egnede mengder av den aktive komponent. Enhetsdoseringsformen kan være et forpakket preparat hvor pakken inneholder atskilte mengder av preparatet, slik som forpakkede tabletter, kapsler og pulvere i ampuller. Enhetsdoseringsformen kan også være en kapsel, tablett, pose eller pastill i seg selv, eller kan være det egnede antall av enhver av disse i forpakket form.
Mengden av aktiv komponent i et enhetsdosepreparat kan varieres eller justeres fra 0,1 mg til 100 mg, fortrinnsvis 0,5 mg til 100 mg i henhold til den bestemte anvendelse og styrken av den aktive komponent. Preparatet kan, om ønsket, også inneholde andre forenlige terapeutiske midler.
I terapeutisk bruk ved behandling av risikopopula-sjoner, slik som de med svekket glukosetoleranse, for å forhindre eller forsinke starten av NIDDM og komplikasjoner som oppstår derfra, administreres forbindelsene anvendt i de farmasøytiske metoder ifølge oppfinnelsen, sammen med en farmasøytisk aksept-abel bærer i begynnelsesdoser på ca. 0,01 mg til ca. 20 mg pr. kg daglig. Et daglig doseområde på ca. 0,01 mg til ca. 10 mg pr. kg er foretrukket. Dosene kan imidlertid varieres avhengig av pasientens krav, strengheten av den tilstand som behandles og den forbindelse som anvendes. Bestemmelse av den riktige dose for en bestemt situasjon hører til fagmannens kunnskap. Generelt startes behandlingen med mindre doser som er mindre enn den optimale dose av forbindelsen. Dosen økes deretter i små intervaller, inntil den optimale effekt under de rådende omstendigheter nås. Hen-siktsmessig kan den totale daglige dose oppdeles og administreres i porsjoner i løpet av dagen, om ønsket.
Forbindelsen er verdifulle midler til å gjenopprette et individ til en tilstand med glukosetoleranse og derfor forhindre eller forsinke starten av NIDDM.
Claims (1)
- Anvendelse av forbindelsen 5-[4-[2-(5-etylpyridin-2-yl)etoksy]benzyl]tiazolidin-2,4-dion (pioglitazone) eller et farmasøytisk akseptabelt salt derav, ved fremstilling av et medikament for behandling av svekket glukosetoleranse for å forhindre eller forsinke starten av ikke-insulinavhengig diabetes mellitus i en pasient som lider av svekket glukosetoleranse.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12225193A | 1993-09-15 | 1993-09-15 | |
US08293899 US5478852C1 (en) | 1993-09-15 | 1994-08-23 | Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus |
PCT/US1994/010389 WO1995007694A1 (en) | 1993-09-15 | 1994-09-14 | Use of thiazolidinediones to prevent or delay onset of niddm |
Publications (3)
Publication Number | Publication Date |
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NO2963A NO2963A (no) | 1996-05-14 |
NO20002963D0 NO20002963D0 (no) | 2000-06-09 |
NO314748B1 true NO314748B1 (no) | 2003-05-19 |
Family
ID=26820333
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
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NO19961041A NO310097B1 (no) | 1993-09-15 | 1996-03-14 | Anvendelse av tiazolidindioner for fremstilling av et medikament for å forhindre eller forsinke starten av NIDDM |
NO20002963A NO314748B1 (no) | 1993-09-15 | 2000-06-09 | Anvendelse av forbindelsen 5-[4-[2-(5-etylpyridin-2-yl)- etoksy]benzyl]tiazolidin-2,4-dion (pioglitazone) for fremstilling av et medikamentfor behandling av svekket glukosetoleranse |
NO20002964A NO314747B1 (no) | 1993-09-15 | 2000-06-09 | Anvendelse av tiazolidinonderivater for fremstilling av et medikament for behandling av svekket glukosetoleranse |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
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NO19961041A NO310097B1 (no) | 1993-09-15 | 1996-03-14 | Anvendelse av tiazolidindioner for fremstilling av et medikament for å forhindre eller forsinke starten av NIDDM |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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NO20002964A NO314747B1 (no) | 1993-09-15 | 2000-06-09 | Anvendelse av tiazolidinonderivater for fremstilling av et medikament for behandling av svekket glukosetoleranse |
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EP (2) | EP0719140B1 (no) |
JP (3) | JP3081245B2 (no) |
CN (3) | CN1103590C (no) |
AT (1) | ATE376829T1 (no) |
AU (3) | AU679572B2 (no) |
CA (1) | CA2171827C (no) |
CZ (1) | CZ283339B6 (no) |
DK (1) | DK0719140T3 (no) |
ES (1) | ES2296288T3 (no) |
FI (1) | FI961213A (no) |
HK (1) | HK1011925A1 (no) |
HU (1) | HU228260B1 (no) |
NO (3) | NO310097B1 (no) |
NZ (1) | NZ274346A (no) |
RU (1) | RU2195282C2 (no) |
WO (1) | WO1995007694A1 (no) |
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US5874454A (en) * | 1993-09-15 | 1999-02-23 | Warner-Lambert Company | Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus |
US6046222A (en) * | 1993-09-15 | 2000-04-04 | Warner-Lambert Company | Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus |
US7115728B1 (en) | 1995-01-30 | 2006-10-03 | Ligand Pharmaceutical Incorporated | Human peroxisome proliferator activated receptor γ |
AU2381397A (en) * | 1996-04-19 | 1997-11-12 | Novo Nordisk A/S | Modulators of molecules with phosphotyrosine recognition units |
US5958957A (en) * | 1996-04-19 | 1999-09-28 | Novo Nordisk A/S | Modulators of molecules with phosphotyrosine recognition units |
EP0930882A2 (en) * | 1996-08-02 | 1999-07-28 | Institut Pasteur De Lille | Prevention or treatment of type 2 diabetes or cardiovascular disease with ppar modulators |
DE69738809D1 (de) * | 1996-11-08 | 2008-08-14 | Nippon Chemiphar Co | Mittel zur verringerung der eigeweidefette |
AU754479B2 (en) * | 1997-05-15 | 2002-11-14 | Warner-Lambert Company | Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome and gestational diabetes |
GB9712866D0 (en) * | 1997-06-18 | 1997-08-20 | Smithkline Beecham Plc | Novel method of treatment |
HUP9902721A2 (hu) | 1997-11-25 | 1999-12-28 | The Procter & Gamble Co. | Tömény textillágyító készítmény és ehhez alkalmazható magas telítetlenségű textillágyító vegyület |
GB9824893D0 (en) * | 1998-11-12 | 1999-01-06 | Smithkline Beckman Corp | Novel method of treatment |
AU2002314744A1 (en) | 2001-04-17 | 2002-10-28 | Sepracor, Inc. | Thiazole and other heterocyclic ligands and use thereof |
US6531461B1 (en) * | 2001-06-04 | 2003-03-11 | Louis Obyo Obyo Nelson | Medicament for the treatment of diabetes |
US6794401B2 (en) * | 2003-01-17 | 2004-09-21 | Bexel Pharmaceuticals, Inc. | Amino acid phenoxy ethers |
MXPA05007883A (es) | 2003-01-29 | 2005-09-21 | Takeda Pharmaceutical | Proceso para producir una preparacion recubierta. |
JP4567340B2 (ja) * | 2003-01-29 | 2010-10-20 | 武田薬品工業株式会社 | 被覆製剤の製造方法 |
ZA200506397B (en) * | 2003-01-29 | 2006-11-29 | Takeda Pharmaceutical | Process for producing coated preparation |
FR2858321B1 (fr) * | 2003-07-28 | 2006-01-20 | Servier Lab | Nouveaux derives d'oximes heterocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
WO2006080524A1 (ja) * | 2005-01-31 | 2006-08-03 | Ajinomoto Co., Inc. | 血糖降下剤を含有する、耐糖能異常、境界型糖尿病、インスリン抵抗性及び高インスリン血症の改善ないし治療用医薬組成物 |
PL2902026T3 (pl) * | 2006-03-16 | 2018-03-30 | Metabolic Solutions Development Company Llc | Analogi tiazolidynodionu do leczenia choroby metabolicznej pośredniczonej przez zapalenie |
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JPS5522636A (en) * | 1978-08-04 | 1980-02-18 | Takeda Chem Ind Ltd | Thiazoliding derivative |
JPS6051189A (ja) * | 1983-08-30 | 1985-03-22 | Sankyo Co Ltd | チアゾリジン誘導体およびその製造法 |
AR240698A1 (es) * | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
US4873255A (en) * | 1987-02-04 | 1989-10-10 | Sankyo Company Limited | Thiazolidinone derivatives, their preparation and their use |
DE3856378T2 (de) * | 1987-09-04 | 2000-05-11 | Beecham Group Plc | Substituierte Thiazolidindionderivate |
US5061717A (en) * | 1988-03-08 | 1991-10-29 | Pfizer Inc. | Thiazolidinedione hypoglycemic agents |
WO1989008651A1 (en) * | 1988-03-08 | 1989-09-21 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
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GB8919417D0 (en) * | 1989-08-25 | 1989-10-11 | Beecham Group Plc | Novel compounds |
GB8919434D0 (en) * | 1989-08-25 | 1989-10-11 | Beecham Group Plc | Novel compounds |
JP2826379B2 (ja) * | 1990-01-22 | 1998-11-18 | 三共株式会社 | チアゾリジン誘導体を有効成分とする肥満性高血圧症治療剤 |
GB9023583D0 (en) * | 1990-10-30 | 1990-12-12 | Beecham Group Plc | Novel compounds |
GB9023585D0 (en) * | 1990-10-30 | 1990-12-12 | Beecham Group Plc | Novel compounds |
ATE142631T1 (de) * | 1991-06-25 | 1996-09-15 | Pfizer | Thiazolidindione als hypoglykämische wirkstoffe |
FR2680512B1 (fr) * | 1991-08-20 | 1995-01-20 | Adir | Nouveaux derives de 2,4-thiazolidinedione, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
FR2688220A1 (fr) * | 1992-03-06 | 1993-09-10 | Adir | Nouveaux derives de thiazolidine-2,4-dione, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
-
1994
- 1994-09-14 HU HU9600653A patent/HU228260B1/hu unknown
- 1994-09-14 WO PCT/US1994/010389 patent/WO1995007694A1/en active IP Right Grant
- 1994-09-14 EP EP94929204A patent/EP0719140B1/en not_active Expired - Lifetime
- 1994-09-14 AU AU78351/94A patent/AU679572B2/en not_active Expired
- 1994-09-14 RU RU96108256/14A patent/RU2195282C2/ru active
- 1994-09-14 CA CA002171827A patent/CA2171827C/en not_active Expired - Lifetime
- 1994-09-14 EP EP05027984A patent/EP1714652A3/en not_active Withdrawn
- 1994-09-14 NZ NZ274346A patent/NZ274346A/en not_active IP Right Cessation
- 1994-09-14 DK DK94929204T patent/DK0719140T3/da active
- 1994-09-14 ES ES94929204T patent/ES2296288T3/es not_active Expired - Lifetime
- 1994-09-14 JP JP07509333A patent/JP3081245B2/ja not_active Expired - Lifetime
- 1994-09-14 CZ CZ96793A patent/CZ283339B6/cs not_active IP Right Cessation
- 1994-09-14 CN CN94194058A patent/CN1103590C/zh not_active Expired - Lifetime
- 1994-09-14 AT AT94929204T patent/ATE376829T1/de active
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1996
- 1996-03-14 NO NO19961041A patent/NO310097B1/no not_active IP Right Cessation
- 1996-03-15 FI FI961213A patent/FI961213A/fi unknown
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1997
- 1997-04-03 AU AU17709/97A patent/AU706947B2/en not_active Expired
- 1997-04-03 AU AU17710/97A patent/AU1771097A/en not_active Abandoned
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1998
- 1998-12-09 HK HK98113005A patent/HK1011925A1/xx not_active IP Right Cessation
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2000
- 2000-03-15 JP JP2000071977A patent/JP2000273043A/ja active Pending
- 2000-03-15 JP JP2000071978A patent/JP2000239167A/ja active Pending
- 2000-06-09 NO NO20002963A patent/NO314748B1/no not_active IP Right Cessation
- 2000-06-09 NO NO20002964A patent/NO314747B1/no not_active IP Right Cessation
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2002
- 2002-05-28 CN CNB021219435A patent/CN1202823C/zh not_active Expired - Lifetime
- 2002-05-28 CN CNB021219427A patent/CN1202821C/zh not_active Expired - Lifetime
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