DK150604B - Analogifremgangsmaade til fremstilling af calciumoxaprozin - Google Patents
Analogifremgangsmaade til fremstilling af calciumoxaprozin Download PDFInfo
- Publication number
- DK150604B DK150604B DK183582A DK183582A DK150604B DK 150604 B DK150604 B DK 150604B DK 183582 A DK183582 A DK 183582A DK 183582 A DK183582 A DK 183582A DK 150604 B DK150604 B DK 150604B
- Authority
- DK
- Denmark
- Prior art keywords
- calcium
- oxaprozin
- oxaprozine
- salt
- preparing calcium
- Prior art date
Links
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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
o χ 150SG4
Den foreliggende opfindelse angår en analogifremgangs-måde til fremstilling af dét hidtil ukendte calciumoxaprozin.
Oxaprozin, nemlig 3“(4,5-diphenyloxazol-2-yl)propion-syre har vist interessant antiinflammatorisk aktivitet og 5 er for tiden ved at undergå kliniske forsøg ved afprøvning på mennesker som antiinflammatorisk middel.
Uheldigvis har oxaprozin en meget bitter smag. Dette kan maskeres i brug ved at lave doseringsformerne som kapsler eller filmovertrukne tabletter. Hvor der imidlertid kræves 10 meget store enkeltdoser af oxaprozin, er denne løsning på problemet ikke. tilfredsstillende. Forsøg er derfor gennemført for at finde frem til farmaceutiske præparater, der tillader heldagsdosering på én gang. Sådanne præparater indbefatter tyggetabletter indeholdende en forholdsvis stor mængde oxaprozin 15 og suspensioner. Oxaprozins bitre smag har vist sig at være en ulempe hos sådanne præparater.
Der er nu fremstillet forskellige salte af oxaprozin, hvoraf ét ved den herved foretagne forskning har vist sig at overvinde ovenstående mangler, idet det er konstateret, at 20 calciumsaltet ikke har stamsyrens bitterhed. Derimod er oxaprozins natriumsalt på den anden side ganske bittert.
Ifølge den foreliggende opfindelse tilvejebringes derfor en fremgangsmåde til fremstilling af calciumoxaprozin, dvs. calciumsaltet af 3-(4,5-diphenyloxazol-2-yl)propionsyre, hvil-25 ken fremgangsmåde er ejendommelig ved, at oxaprozin, fortrinsvis i form af et vandopløseligt salt, navnlig et alkalimetalsalt, behandles med en kilde til calciumioner, især calcium-chlorid, fortrinsvis ved at omsættes i vandig opløsning.
Det vandopløselige salt kan ud over et alkalimetalsalt, 30 f.eks. natrium- eller kaliumsaltet, være et ammoniumsalt eller et aminsalt. Kilden til calciumioner kan ud over calciumchlo-rid f.eks. være calciumnitrat, calciumacetat eller calcium-formiat i vandig opløsning.
Betegnelsen calciumoxaprozin omfatter alle former af calciumoxaprozin, inklusive tetrahydratet, som fremkommer under visse omstændigheder.
o 150604
Det her omhandlede calciumoxaprozin kan anvendes i et velsmagende farmaceutisk præparat til oral indgivelse, hvilket præparat foruden calciumoxaprozin indeholder en farmaceutisk bærer.
5 De farmaceutiske præparater indbefatter faste og fly dende sammensætninger. En hvilken som helst hensigtsmæssig bærer, som er kendt inden for teknikken, kan anvendes i det farmaceutiske middel. I et sådant middel er bæreren almindeligvis fast eller flydende eller foreligger som en blanding 10 af et fast eller flydende bærestof.
Fortrinsvis foreligger den farmaceutiske sammensætning i enhedsdoseringsform såsom tabletter eller kapsler. I en sådan form er midlet underinddelt i enhedsdoser indeholdende passende mængder af den aktive bestanddel. Mængden af aktiv 15 bestanddel i en enhedsdosisform kan varieres eller indstilles fra 100 mg eller mindre til 800 mg eller mere, alt i overensstemmelse med det særlige behov. Fortrinsvis er calciumoxaprozin til stede i en mængde fra 200 til 750 mg, men især fra 400 til 750 mg.
20
Eksempel β-(4,5-diphenyioxazol-2-yl)propionsyrecalciumsalt β-(4,5-diphenyloxazol-2-yl)propionsyre ("oxaprozin") omdannes til sit natriumsalt ved at omrøre syren (6 kg) i 25 60 kg destilleret vand og 1,85 kg 46 til 48%'s flydende na triumhydroxid. En filtreret opløsning af 2,44 kg calcium-chlorid-dihydrat B.P. (British Pharmacopeia) i destilleret vand tilsættes, og den i overskriften anførte forbindelse fældes som et hvidt fast stof. Dette indsamles på vakuumfilter 30 og vaskes med destilleret vand, indtil filtratet er chlorid-frit. Produktet tørres i luftovn, hvilket giver et udbytte på 6,7 kg (98% af det teoretiske) af den i overskriften anførte forbindelse som tetrahydrat.
35
3 1506 0A
o
Analyse, beregnet for (^8^4^3^ 2 Ca, 41^0: C = 62,0%, H = 5,17%, N = 4,02% fundet: C = 61,48%, H = 5,02%, N = 3,67%. Calciumindholdet er ved gravimetrisk analyse bestemt 5 til 6,4% (teoretisk calciumindhold 5,75%).
Forsøg
Calciumsaltet fra eksempel 1 bringes på præparatform som tyggetabletter. Disse viser sig at være ganske velsmagen-10 de i modsætning til lignende oxaprozintabletter, der er så bitre, at de faktisk ikke er til at holde ud at have i munden.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8113074 | 1981-04-28 | ||
GB8113074 | 1981-04-28 |
Publications (3)
Publication Number | Publication Date |
---|---|
DK183582A DK183582A (da) | 1982-10-29 |
DK150604B true DK150604B (da) | 1987-04-13 |
DK150604C DK150604C (da) | 1987-12-07 |
Family
ID=10521427
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK183582A DK150604C (da) | 1981-04-28 | 1982-04-23 | Analogifremgangsmaade til fremstilling af calciumoxaprozin |
Country Status (24)
Country | Link |
---|---|
US (2) | US4465838A (da) |
EP (1) | EP0063884B1 (da) |
JP (1) | JPS57181072A (da) |
KR (1) | KR880000871B1 (da) |
AT (1) | ATE14015T1 (da) |
AU (1) | AU544975B2 (da) |
CA (1) | CA1169867A (da) |
CS (1) | CS236674B2 (da) |
DD (1) | DD202017A5 (da) |
DE (1) | DE3264400D1 (da) |
DK (1) | DK150604C (da) |
ES (1) | ES8307230A1 (da) |
FI (1) | FI71314C (da) |
GR (1) | GR75913B (da) |
HU (1) | HU185276B (da) |
IE (1) | IE52909B1 (da) |
IL (1) | IL65443A (da) |
MY (1) | MY8700599A (da) |
NZ (1) | NZ200247A (da) |
PH (1) | PH18053A (da) |
PL (1) | PL136322B1 (da) |
PT (1) | PT74794B (da) |
ZA (1) | ZA822355B (da) |
ZW (1) | ZW7482A1 (da) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5380738A (en) * | 1993-05-21 | 1995-01-10 | Monsanto Company | 2-substituted oxazoles further substituted by 4-fluorophenyl and 4-methylsulfonylphenyl as antiinflammatory agents |
US6726928B2 (en) * | 1994-10-28 | 2004-04-27 | R.P. Scherer Technologies, Inc. | Process for preparing solid dosage forms for unpalatable pharmaceuticals |
KR20000015865A (ko) * | 1996-05-20 | 2000-03-15 | 윌리암스 로저 에이 | 칼륨, 나트륨 및 트리스옥사프로진염의 약학적 제제 |
US7358254B2 (en) * | 2001-07-13 | 2008-04-15 | Bristol-Myers Squibb Company | Method for treating atherosclerosis employing an aP2 inhibitor and combination |
US20060222671A1 (en) * | 2005-03-30 | 2006-10-05 | Astion Development A/S | Dermatological compositions and salts for the treatment of dermatological diseases |
AU2006228869A1 (en) * | 2005-03-30 | 2006-10-05 | Astion Pharma A/S | Oxaprozin or a closely related compound for the treatment of eczema |
DK2340296T3 (da) * | 2008-08-26 | 2015-01-19 | Dorf Ketal Chemicals I Private Ltd | Nyt additiv til inhibering af syrekorrosion og fremgangsmåder til anvendelse af det nye additiv |
KR20140065862A (ko) * | 2012-11-22 | 2014-05-30 | 에스케이케미칼주식회사 | 발포성 속붕해성 이매티닙 제제 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1206403A (en) * | 1966-12-15 | 1970-09-23 | Wyeth John & Brother Ltd | Oxazoles |
GB1245087A (en) * | 1967-10-26 | 1971-09-02 | Wyeth John & Brother Ltd | Heterocyclic compounds |
US3578671A (en) * | 1967-11-06 | 1971-05-11 | Wyeth John & Brother Ltd | Oxazoles |
-
1982
- 1982-03-31 IE IE766/82A patent/IE52909B1/en not_active IP Right Cessation
- 1982-04-05 CA CA000400464A patent/CA1169867A/en not_active Expired
- 1982-04-05 ZA ZA822355A patent/ZA822355B/xx unknown
- 1982-04-06 NZ NZ200247A patent/NZ200247A/en unknown
- 1982-04-06 IL IL65443A patent/IL65443A/xx not_active IP Right Cessation
- 1982-04-06 AU AU82378/82A patent/AU544975B2/en not_active Expired
- 1982-04-07 EP EP82301839A patent/EP0063884B1/en not_active Expired
- 1982-04-07 AT AT82301839T patent/ATE14015T1/de not_active IP Right Cessation
- 1982-04-07 DE DE8282301839T patent/DE3264400D1/de not_active Expired
- 1982-04-09 GR GR67879A patent/GR75913B/el unknown
- 1982-04-15 ZW ZW74/82A patent/ZW7482A1/xx unknown
- 1982-04-15 FI FI821324A patent/FI71314C/fi not_active IP Right Cessation
- 1982-04-22 PH PH27171A patent/PH18053A/en unknown
- 1982-04-23 JP JP57069463A patent/JPS57181072A/ja active Granted
- 1982-04-23 DK DK183582A patent/DK150604C/da not_active IP Right Cessation
- 1982-04-26 US US06/371,904 patent/US4465838A/en not_active Expired - Lifetime
- 1982-04-26 PL PL1982236145A patent/PL136322B1/pl unknown
- 1982-04-26 PT PT74794A patent/PT74794B/pt unknown
- 1982-04-26 KR KR8201829A patent/KR880000871B1/ko active
- 1982-04-27 DD DD82239350A patent/DD202017A5/de not_active IP Right Cessation
- 1982-04-27 ES ES511730A patent/ES8307230A1/es not_active Expired
- 1982-04-27 HU HU821325A patent/HU185276B/hu unknown
- 1982-04-28 CS CS823052A patent/CS236674B2/cs unknown
-
1984
- 1984-07-11 US US06/629,704 patent/US4532253A/en not_active Expired - Lifetime
-
1987
- 1987-12-30 MY MY599/87A patent/MY8700599A/xx unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DK175544B1 (da) | Anvendelse af azithromycin og derivater deraf til fremstilling af antiprotozoale lægemidler | |
US4956386A (en) | Pharmaceutical compositions and process for their preparation | |
CA1040532A (en) | Process for producing solid bismuth-containing pharmaceutical compositions | |
ZA831452B (en) | Cephalosporing derivatives,and a process for their preparation | |
US2791609A (en) | Tetracycline metallo-phosphate complexes and method preparation | |
DK150604B (da) | Analogifremgangsmaade til fremstilling af calciumoxaprozin | |
US2848366A (en) | Non-hydrated ferrous fumarate and hematinic composition thereof | |
ES443616A1 (es) | Procedimiento para la fabricacion de nuevos derivados 1,3- disustituidos del propanol-(2) y sus esteres de acido nico- tinico. | |
US4073895A (en) | Isopropylamino pyrimidine orthophosphate | |
CA1297033C (en) | Use of carboxylic acid amides for treating inflammations | |
DE2967356D1 (en) | Cephalosporin derivatives, process for their preparation and pharmaceutical compositions containing them | |
SE509694C2 (sv) | Farmaceutiska kompositioner innehållande ranitidin/vismut karboxylsyra salter | |
ES8308833A1 (es) | "un metodo para la preparacion de 3-fenil-1-indanaminas". | |
DK151806B (da) | Analogifremgangsmaade til fremstilling af vincaminsaccharinat | |
EP0030023A3 (en) | A heterocyclic compound and its synthesis, pharmaceutical formulations thereof and the use of the compounds and the formulations in medicine | |
US3068264A (en) | Tetracycline antibiotic-aluminumphosphoric acid complexes | |
US3155577A (en) | Tasteless dioctylsulfosuccinate composition and method of making same | |
US2736735A (en) | Tetracycline antibiotic zirconium hydroxyacid complexes | |
IE51517B1 (en) | Drug combination for the treatment of infectious diseases of the respiratory tract | |
US2794762A (en) | Body deodorant for internal use | |
US3501577A (en) | Method of treating hypertension with alkali metal salts of zinc diethylenetriaminepentaacetate | |
US2220692A (en) | Process of making ammonium mandelate | |
DE2706841C2 (da) | ||
US3956279A (en) | Crystalline pivaloyloxymethyl d(-)-α-aminobenzylpenicillinate | |
US4243679A (en) | S-(3-Methyl-2-butenyl)cysteine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUP | Patent expired |