SI8810183A8 - Postopek za pridobivanje kristalne natrijeve soli 5-klor-3-(2-tenoil)-2-oksindol-1-karboksamida - Google Patents
Postopek za pridobivanje kristalne natrijeve soli 5-klor-3-(2-tenoil)-2-oksindol-1-karboksamida Download PDFInfo
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- SI8810183A8 SI8810183A8 SI8810183A SI8810183A SI8810183A8 SI 8810183 A8 SI8810183 A8 SI 8810183A8 SI 8810183 A SI8810183 A SI 8810183A SI 8810183 A SI8810183 A SI 8810183A SI 8810183 A8 SI8810183 A8 SI 8810183A8
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- carboxamide
- oxindole
- chloro
- thenoyl
- sodium salt
- Prior art date
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- 159000000000 sodium salts Chemical class 0.000 title claims description 7
- IGPDWKCUDHIIRL-UHFFFAOYSA-N 5-chloro-2-oxo-3-[oxo(thiophen-2-yl)methyl]-3H-indole-1-carboxamide Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)C1C(=O)C1=CC=CS1 IGPDWKCUDHIIRL-UHFFFAOYSA-N 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
- 150000003839 salts Chemical group 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- -1 2-thenoyl Chemical group 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000000113 differential scanning calorimetry Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- SUSZLUNAEWTDEY-UHFFFAOYSA-M sodium;5-chloro-2-oxo-3-(thiophene-2-carbonyl)-3h-indole-1-carboximidate Chemical compound [Na+].C12=CC(Cl)=CC=C2N(C(=O)[NH-])C(=O)C1C(=O)C1=CC=CS1 SUSZLUNAEWTDEY-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- OMWYWPNJQWIJRG-UHFFFAOYSA-N 5-chloro-3-(thiophene-2-carbonyl)-1,3-dihydroindol-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)C1C(=O)C1=CC=CS1 OMWYWPNJQWIJRG-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- WVQQNVZRUPAGHP-UHFFFAOYSA-N O.[Na].ClC=1C=C2C(C(N(C2=CC1)C(=O)N)=O)C(C1=CC=CS1)=O Chemical compound O.[Na].ClC=1C=C2C(C(N(C2=CC1)C(=O)N)=O)C(C1=CC=CS1)=O WVQQNVZRUPAGHP-UHFFFAOYSA-N 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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]
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pain & Pain Management (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)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
POSTUPAK ZA DOBIJANJE ANHIDROVANE, KRISTALNE NATRIJUMOVE SOLI 5-HL0R-3-(2-TENOIL)-2-0KSINDOL-1-KARBOKSAMIDA
Oblast tehnike
Ovaj pronalazak spada u oblast postupaka za dobijanje anhidrovanih kristalnih soli uopšte, a posebno u oblast dobijanja soli karboksamida. Prema MKP pronalazak ima oznaku C 07D 409/02 i A61K 31/40.
>··
Tehnički problem
Tehnički problem koji se ovim pronalaskom rešava Jeste kako izvesti postupak za dobijanje kristalnog oblika natrijumove soli 5-hlor-3-(2-tenoil)-2-oksindol-l-karboksamida, koji ima pogodne reološke i elektrostatičke osobine za pripremanje famaceutskih formulacija.
Stanje tehnike
Kadin, Je u U.S. patentu 4,566,672 opisao 5-hlor-3-(2-tenoil)-2-oksindol -1-karboksamid, formule I
nh2 i
(ili famaceutski prihvatljivu so), kao posebno pogodno jedinjenje za upotrebu kao analgetsko ili antiinflamatorno sredstvo. Prema tom ponalasku, natrijumova so jedinjenja formule (I) je alternativno izolovana kao hemihidrat ili hidrat. Monohidrat je anhidrovan daljim sušenjem. Utvrdjeno je da se obrazuje nekoliko hidrata koji se nalaze u obliku smesa sa različitim morfologijama (npr. amorfni 1 kristali u obliku iglica). Ovi različito hidratisani oblici imaju takve reološke i elektrostatičke osobine koje formulaciju (odn. sastav u kome se preparat daje pacijentu u odredjenom obliku, kao što je kapsula, tableta i sl.) čini nepogodnom.
Opis rešenja tehničkog problema
Sada je pronadjen anhidrovani, kristalni oblik natrijumove soli 5-hlor-3-(2-tenoil)-2-oksindol-l-karboksamida, koji poseduje vredne 1 nepredvidjene osobine. Tako, ova so je laka za rukovanje i formulisanje u oblike kao što su kapsule. Ona nije higroskopna, ostaje stabilna u jedini čnim oblicima u koje se formul iše čak pri 90% vlažnosti. Kada se presuje u obliku tableta, rastvara se brže od hidratisane soli.
Ova korisna kristalna so ,se formuliše i upotrebljava kao analgetik prema ranijem izlaganju od strane Kadina, kao što je gore citirano, a ovde pomenuto kao referenca.
Neočekivano, ova so se Jednostavno dobija mešanjem hidratisanog oblika natrijumove soli u acetonitrilu na temperaturi okoline. Ovo pretvaranje nije zapaženo u drugom rastvaraču na toj temepraturi, mada se odvija u refluktujučem toluenu, a što Je manje pogodno.
Sadašnji pronalazak izvodi se na jednostavan način. Prema ovom postupku, natrijumova so jedinjenja formule (I) se na pogodan način najpre izoluje u obliku njegovog hidrata, koji se zatim jednostavno meša u acetonitrilu radi dobijanja ove korisne, anhidrovane, nehigroskopne, kristalne natrijumove soli. Temperatura za ovo pretvaranje u acetonitrilu nije kritična, ali se uobičajeno vrši na temperaturi okoline, izbegavajuči energetske troškove 'ili zagrevanje ili iiladjenja. Pretvaranje se alternativno, ali manje pogodno izvodi u toluenu uz azeotropno otklanjanje vode pomoču Dean-Stark-ovog nastavka na temperaturi refluksa toluena. Kako je benzen, koji ključa na nižoj temperaturi, mnogo manje efikasan u ovom postupku, uopšte proizvodeči anhidrovani produkt koji je amorfan, smatra se da je upotreba viših temperatura kritična za obrazovanje anhidrovanog kristala, kada rastvarač nije acetonitril.
Kristalna so prema ovom pronalasku je okarakterisana svojim posebnim fizičkim svojstvima, kao što je prethodno navedeno. Ona se unosi u razne oblike u kojima se daje pacijentima na način na koji je to ranije opisao Kadin, kao što je prethodno pomenuto. Primeri koji slede su dati radi ilustracije i ne predstavljaju ograničenje ovog pronalaska, a promene unutar njegovog opšega i smisla su moguče.
Pripremanje 1.
Hidratis sna natriJumova so 5-hlor-3-(2-tenoil)-2-oksindol-l-karboksamlda
Navedeni hidrati se dobijaju kao što je opisano u primeru 10 prema
Kadinu, U.S. Patent 4,556,672. Alternativno, 5-hlor-3-(2-tenoil)-2-oksindol
-1-karboksamid (Primer 8, prema Kadinu; 51,2g; 0,16 mola se suspenduje u
400 ml CH CN na 40°C. Uporedo, NaHCO (14,1 g; 0,168 mola) se rastvori u 3 3
200 ml vode i zagreje do 40 C. Vruč~ vodeni rastvor se doda vreloj acetonitrilnoj suspenziji tokom 20 minuta, pri čemu se zapaža blago stvaranje pene. Nastali rastvor se meša na 40°C, tretira sa 5 g uglja za obezbojavanje, meša na 25°C tokom 30 minuta i filtruje sa 50 ml 1:1 CH3CN : Hz0 radi ispiranja. Spojeni filtrat i tečnosti od ispiranja se koncentruju u vakuumu na parnom kupatilu pošto se acetonitril zameni sa 200 m. vode do konačne zapremine od oko 500 ml, ohladi do 25°C 1 prvi prinos Izoluje filtriranjem.
Čvrste materije isperu se sa 50 ml vode. Spojeni matični lug i tečnost od ispiranja se upare na 400 ml, pa se dobija drugi prinos. Posle sušenja na vazduhu prvi prinos teži 35,75 g (6,4% vode) i drugi prinos teži 16,77 g (6,2% vode), 90% prinos je korigovan za sadržaj H20. Nivo vode pro računat za monohidrat je 5,0%. DiferenciJalna skanlrajuča kalorimetriJa na ova dva prinosa pokazuju 4 endoterme (na oko 110, 150, 237 i 255).
PRIMER 1
Anhidrovana kristalna natrijumova so 5-hfor-3-(2-tenoll)-2-okslndol
-1-karboksamida
Hldratna natrijumova so 5-hlor-3-(2-tenoil)-2-oksindol-l-karboksamlda (¢2,5 g; dobljena prema alternatlvnom postupku iz Pripremanje 1) se meša na temperaturi okoline u 52,5 ml CH CN. Naslovni proizvod se izoluje filtriranjem, ispira sa 50 ml CH CN, 1 osuši na 55°C u vakuumu, pa se dobija 46,7 g (95%) naslovnog proizvoda, kristalnog pod polarizujučem mikroskopom; diferenciJalna skanirajuča kalorimetrija unutar opsega 50-300 °C, pokazuje jednu oStru izotermu na 255 + 2°C. Analiza izračunato za
C H CIN 0 SNa : C 49,06; H 2,35; N 8,18; S 9,15; Cl 10,34; sulfatni pepeo 14 8 2 3
20,72; Hz0, 0; gubitak pri sušenju u vakuumu na 100°C, 0. Nadjeno: C 48,85; H 2,39; N 8,22; S 9,54; Cl 10,43; sulfatni pepeo, 20,58; Η,,Ο, 0,07. Gubitak pri sušenju u vakuumu na 100°C, 0,07.
Nasuprot hidratnog oblika koji je narandžaste boje, sadašnja anhidrovana Na-so je žute boje.
Uzorcl hidratnog oblika (Pripremanje 1) i sadašnjeg anhidrovanog oblika su redukovani do sitnih čestica 1 presovani u tablete. Ispitivanjem tih tableta utvrdjeno je da je brzina rastvranja anhidrovanog oblika soli oko tri puta veča od brzine rastvaranja hidratnog oblika soli u istim uslovima. Ista anhidrovana so upotrebljena Je za pripremanje smese kojom se pune želatinske kapsule. Kapsule ispunjene tom solju pokazuju izvrsnu biološku korisnost, kada se oralno primene kod pasa, gde je nivo sadržaja u krvi čak do 89% u odnosu na rastvor koji se oralno daje.
Claims (1)
1. Postupak za dobijanje anhidrovane, kristalne natrijumove soli 5-hlor-3-(2-tenoil)-2-oksindol-l-karboksajnida, naznačen time, što se odgovarajuči hidratnl oblik soli meša sa acetonitrilom na sobnoj temperaturi, a zatim se dobijeni proizvod filtrira, ispira sa acetonitrilom i suši u vakuumu na 55°C.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1987/000201 WO1988005656A1 (en) | 1987-02-02 | 1987-02-02 | Anhydrous, crystalline sodium salt of 5-chloro-3-(2-thenoyl)-2-oxindole-1-carboxamide |
| YU18388A YU46766B (sh) | 1987-02-02 | 1988-02-01 | Postupak za dobijanje anhidrovane, kristalne natrijumove soli 5-hlor-3-(2-tenoil)-2-ok-sindol-1-karboksamida |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI8810183A8 true SI8810183A8 (sl) | 1996-08-31 |
Family
ID=22202263
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI8810183A SI8810183A8 (sl) | 1987-02-02 | 1988-02-01 | Postopek za pridobivanje kristalne natrijeve soli 5-klor-3-(2-tenoil)-2-oksindol-1-karboksamida |
Country Status (42)
| Country | Link |
|---|---|
| US (1) | US5036099A (sl) |
| EP (1) | EP0277738B1 (sl) |
| JP (1) | JPS63201184A (sl) |
| KR (1) | KR900001422B1 (sl) |
| CN (1) | CN1022324C (sl) |
| AP (1) | AP52A (sl) |
| AR (1) | AR243182A1 (sl) |
| AT (1) | ATE73800T1 (sl) |
| AU (1) | AU587736B2 (sl) |
| BG (1) | BG51042A3 (sl) |
| CA (1) | CA1335590C (sl) |
| CS (2) | CS265250B2 (sl) |
| CY (1) | CY1775A (sl) |
| DD (1) | DD267490A5 (sl) |
| DE (1) | DE3869149D1 (sl) |
| DK (1) | DK44888A (sl) |
| EC (1) | ECSP941082A (sl) |
| ES (1) | ES2032955T3 (sl) |
| FI (1) | FI89598C (sl) |
| GR (1) | GR3004200T3 (sl) |
| HK (1) | HK132695A (sl) |
| IE (1) | IE60000B1 (sl) |
| IL (1) | IL85277A (sl) |
| IN (1) | IN171799B (sl) |
| IS (1) | IS1533B (sl) |
| LV (1) | LV10252B (sl) |
| MA (1) | MA21171A1 (sl) |
| MY (1) | MY102737A (sl) |
| NO (1) | NO170581C (sl) |
| NZ (1) | NZ223373A (sl) |
| OA (1) | OA08710A (sl) |
| PH (1) | PH26545A (sl) |
| PL (1) | PL149550B1 (sl) |
| PT (1) | PT86675B (sl) |
| RO (1) | RO105052B1 (sl) |
| RU (1) | RU2011381C1 (sl) |
| SG (1) | SG27994G (sl) |
| SI (1) | SI8810183A8 (sl) |
| UA (1) | UA25898A1 (sl) |
| WO (1) | WO1988005656A1 (sl) |
| YU (1) | YU46766B (sl) |
| ZA (1) | ZA88679B (sl) |
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| US4861794A (en) * | 1988-04-13 | 1989-08-29 | Pfizer Inc. | 3-substituted-2-oxindole-1-carboxamides as inhibitors of interleukin-1 biosynthesis |
| US4853409A (en) * | 1988-04-13 | 1989-08-01 | Pfizer Inc. | 3-substituted-2-oxindole-1-carboxamides for suppressing T-cell function |
| US5118703A (en) * | 1988-10-18 | 1992-06-02 | Pfizer Inc. | Prodrugs of antiinflammatory 3-acyl-2-oxindole-1-carboxamides |
| DE68923673T2 (de) * | 1988-10-18 | 1996-01-18 | Pfizer | Prodrogen von antiinflammatorischen 3-Acyl-2-oxindol-1-carboxamiden. |
| US5059693A (en) * | 1989-10-06 | 1991-10-22 | Pfizer Inc. | Process for making 3-aroyl-2-oxindole-1-carboxamides |
| US5008283A (en) * | 1990-03-19 | 1991-04-16 | Pfizer Inc. | Use of tenidap to inhibit activation of collagenase and to inhibit the activity of myeloperoxidase |
| US5006547A (en) * | 1990-03-19 | 1991-04-09 | Pfizer Inc. | Tenidap as an inhibitor of the release of elastase by neutrophils |
| US5122534A (en) * | 1991-02-08 | 1992-06-16 | Pfizer Inc. | Use of tenidap to reduce total serum cholesterol, ldl cholesterol and triglycerides |
| DE4111305C2 (de) * | 1991-04-08 | 1994-12-01 | Mack Chem Pharm | Pharmazeutische Zubereitung zur rektalen Applikation, die ein 2-Oxindol-l-carboxamid-derivat enthält |
| TW438798B (en) * | 1992-10-07 | 2001-06-07 | Pfizer | 3-substituted 2-oxindole-1-carboxamide pharmaceutical compositions |
| US5270331A (en) * | 1993-01-26 | 1993-12-14 | Pfizer, Inc. | Prodrugs of antiinflammatory 3-acyl-2-oxindole-1-carboxamides |
| AU7503496A (en) * | 1995-12-19 | 1997-07-14 | Pfizer Inc. | Stable, long acting salts of indole derivatives for the treatment of joint diseases |
| EP0826685A1 (en) * | 1996-08-21 | 1998-03-04 | Pfizer Inc. | Stable, long acting salts of carboxamides for the treatment of joint disease |
| DE19854355A1 (de) * | 1998-11-25 | 2000-05-31 | Bayer Ag | Kristallmodifikation B von 8-Cyan-1-cyclopropyl-7-(1S, 6S-2,8-diazabicyclo-/4.3.O/nonan-8-yl)-6-fluor-1,4-dihydro-4-oxo-3-chinolincarbonsäure |
| US7407195B2 (en) | 2004-04-14 | 2008-08-05 | William Berson | Label for receiving indicia having variable spectral emissivity values |
| US7651031B2 (en) | 2004-10-25 | 2010-01-26 | William Berson | Systems and methods for reading indicium |
| US7931413B2 (en) * | 2005-01-14 | 2011-04-26 | William Berson | Printing system ribbon including print transferable circuitry and elements |
| US7728726B2 (en) * | 2005-01-14 | 2010-06-01 | William Berson | Radio frequency identification labels |
| US7621451B2 (en) * | 2005-01-14 | 2009-11-24 | William Berson | Radio frequency identification labels and systems and methods for making the same |
| US7619520B2 (en) * | 2005-01-14 | 2009-11-17 | William Berson | Radio frequency identification labels and systems and methods for making the same |
| CN111447882B (zh) | 2017-11-02 | 2024-05-24 | 阿克瑞特医学治疗有限公司 | 具有一体式过滤器的栓塞导管 |
| BR112021023510A2 (pt) | 2019-05-23 | 2022-01-18 | Accurate Medical Therapeutics Ltd | Cateter de embolização para distribuição livre de refluxo de microesferas. |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3767653A (en) * | 1971-06-28 | 1973-10-23 | Squibb & Sons Inc | Thiazines |
| GB1532413A (en) * | 1974-12-23 | 1978-11-15 | Union International Co Ltd | Chenodeoxycholic acid |
| DE2613346C3 (de) * | 1976-03-29 | 1981-07-23 | Diamalt AG, 8000 München | Monoklin kristalline Chenodesoxycholsäure und Verfahren zu ihrer Herstellung |
| DE3582890D1 (de) * | 1984-02-07 | 1991-06-20 | Pfizer | 2-oxindolzwischenprodukte. |
| GR850669B (sl) * | 1984-03-19 | 1985-07-25 | Pfizer | |
| US4556672A (en) * | 1984-03-19 | 1985-12-03 | Pfizer Inc. | 3-Substituted 2-oxindole-1-carboxamides as analgesic and anti-inflammatory agents |
| US4569942A (en) * | 1984-05-04 | 1986-02-11 | Pfizer Inc. | N,3-Disubstituted 2-oxindole-1-carboxamides as analgesic and antiinflammatory agents |
-
1987
- 1987-02-02 WO PCT/US1987/000201 patent/WO1988005656A1/en not_active Ceased
- 1987-02-02 UA UA4614718A patent/UA25898A1/uk unknown
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1988
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- 1988-02-02 JP JP63022675A patent/JPS63201184A/ja active Granted
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1989
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1991
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1992
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1993
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1994
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1995
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1996
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Effective date: 20051202 |