DK147671B - Oralt roentgenkontrastmiddel - Google Patents
Oralt roentgenkontrastmiddel Download PDFInfo
- Publication number
- DK147671B DK147671B DK047576AA DK47576A DK147671B DK 147671 B DK147671 B DK 147671B DK 047576A A DK047576A A DK 047576AA DK 47576 A DK47576 A DK 47576A DK 147671 B DK147671 B DK 147671B
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- DK
- Denmark
- Prior art keywords
- buffer
- oral
- acid
- agent
- xentic
- Prior art date
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- 239000002872 contrast media Substances 0.000 description 20
- 239000000872 buffer Substances 0.000 description 16
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 230000036765 blood level Effects 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229930006000 Sucrose Natural products 0.000 description 6
- 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 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 210000003445 biliary tract Anatomy 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 5
- 239000001384 succinic acid Substances 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241001122767 Theaceae Species 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000000232 gallbladder Anatomy 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- IGSPYLOKMDUVEX-UHFFFAOYSA-N 4-[n-ethyl-2,4,6-triiodo-3-(methylamino)anilino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)N(CC)C1=C(I)C=C(I)C(NC)=C1I IGSPYLOKMDUVEX-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 150000003931 anilides Chemical class 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- -1 eg NaHCO3 Chemical class 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 210000003736 gastrointestinal content Anatomy 0.000 description 2
- 229950002482 iosumetic acid Drugs 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 2
- 229960004503 metoclopramide Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- OIRFJRBSRORBCM-YFKPBYRVSA-N (2s)-2-[(3-amino-2,4,6-triiodophenyl)methyl]butanoic acid Chemical compound CC[C@H](C(O)=O)CC1=C(I)C=C(I)C(N)=C1I OIRFJRBSRORBCM-YFKPBYRVSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FJYJNLIEGUTPIJ-UHFFFAOYSA-N Iobenzamic acid Chemical compound NC1=C(I)C=C(I)C(C(=O)N(CCC(O)=O)C=2C=CC=CC=2)=C1I FJYJNLIEGUTPIJ-UHFFFAOYSA-N 0.000 description 1
- OIRFJRBSRORBCM-UHFFFAOYSA-N Iopanoic acid Chemical compound CCC(C(O)=O)CC1=C(I)C=C(I)C(N)=C1I OIRFJRBSRORBCM-UHFFFAOYSA-N 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
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000013189 cholangiography Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229960000963 iobenzamic acid Drugs 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229960005268 tyropanoate Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0447—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
- A61K49/0495—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound intended for oral administration
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/90—In vivo diagnostic or in vivo test agent which contains an additional ingredient to reduce the toxicity or side effects of the active ingredient
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
147671 \
De kendte oralt anvendelige røntgenkontrastmidler til cholecysto= cholangiografi har ikke den diagnostiske værdi som de intravenøst indgivne røntgenkontrastmidler, selv om de er lettere anvendelige og tåles bedre. Røntgenundersøgelsen kan i almindelighed på grund af den langsomme resorption først foretages 12-14 timer efter indtagelse af kontrastmidlet. Den røntgenologiske fremstilling af galdeblæren er mindre kontrastrig end ved de intravenøst indgivne røntgenkontrastmidler. De ekstrahepatiske galdeveje bliver i reglen 2 147671 først ved anvendelse af den såkaldte dobbeltdosis medtaget i et ringe procentisk omfang.
Det var derfor ønskværdigt at udvikle et oralt røntgenkontrast-middel, som udviser en meget god skyggegivende virkning, som specielt også muliggør den samtidige fremstilling af galdevejene og galdeblæren, og ved hvilket den maksimale berigelse i det pågældende organ også tidsmæssigt er fastlagt neje.
For at opnå denne virkning blev kontrastmidlet i en lukket forsøgsrække . først afprøvet eller gennemprøvet på patienter i forhold til kontrolgrupper ved at bringe et samtidig indgivet stort væskevolumen i tarmen og ved yderligere indgivelse af metoclopramid i.v. for at opnå en hurtigere resorp'tion,hvorhos kontrolgruppen fik kontrastmidlet uden yderligere tilsætninger. Herved kunne de påviste ulemper ved de kendte røntgenkontrastmidler ikke overvindes.
Det har nu vist sig, at ved oral applikation af en fysiologisk acceptabel base/puffer eller pufferblanding samtidig med et skyggegivende stof, forøges resorptionen af det skyggegivende stof betydeligt og statistisk signifikant. Dette fremgår af den i tabel 1 viste lukkede forsøgsrække med ravsyre-mcno-2,4,6-trijod-3-methyl-amino-N-ethylanilid som skyggegivende stof og natriumbicarbonat som base/puffer.
Tabel 1
Sammenligning af blodspejlet på fire patientkollektiver efter oral indgivelse af 3 g ravsyre-mono-2,6-tri jod-3-methylamino-N-ethy1= anilid som mikrokrystalsuspension under anvendelse af forskellige supplerende behandlinger (I = ingen, II = 350 ml te, III = 10 mg meto= clopramid i.v. og IV = 3 g natriumbicarbonat)
Blodspejl: O. ΓΙ
Supplerende max max (ft af dosis/
Gruppe. behandling (Min.p.appl.) (mg/100 ml) blodvolumen) I Ingen 132 + 2b 11,½ t b,5 23 ί 8 II 350 ml te 120 t 2b 10,½ i b,2 23 ± 11 III 10 mg metoclo= 96 ± 12 9,7 ± 2,9 30 ± 10 pramid i.v.
IV 3 g natrium= 5b i 12 9,8 ± 2,6 33 ί 3 bicarbonat
Tidspunktet for det maksimale blodspejl ΙΠσ,Χ 147671 3 C : Maksimal koncentration i mg/100 ml henholdsvis procent af max dosisen i det samlede blodvolumen
Middelværdier ± standardafvigelse.
Som det fremgår af tabel 1, giver den yderligere indgivelse af meto= clopramid ingen påviselig indvirkning i forhold til kontrolgruppen. Efter yderligere indgivelse af 3 g natriumbicarbonat opnås det maksimale blodspejl dog allerede 5^ - 12 minutter efter applikationen. Allerede 30 minutter efter indtagelsen var blodspejlet gennemsnitlig steget til 8c$ af maksimalværdien. Forskellen til kollektiverne, som ikke fik base/puffer eller 350 ml te eller 10 mg metoclopramid, er signifikant. Det tidlige tidspunkt for blodspejlsmaksimumet tillader beregningen af eliminationshalveringstiden for kontrastmidlet af blodet, hvilken svarende til patienternes heterogenitet gennemsnitlig udgør 138 ί 84- minutter. Af halveringstiden for elimineringen og tidspunktet for blodspejlsmaksimumet kan man beregne resorptionshalveringstiden til 18 i 6 minutter.
Opfindelsen angår hidtil ukendte orale røntgenkontrastmidler af to komponenter, som er ejendommelige ved, at en af de to komponenter indeholder mindst ét skyggegivende stof, og at den anden komponent indeholder en fysiologisk acceptabel base/puffer eller pufferblanding, hvorhos midlet indeholder 0,5-10 g base/puffer eller pufferblanding pr. dosis skyggegivende stof på 3-10 g. De to komponenter foreligger fortrinsvis i blanding.
Hensigten med tilsætningen er at fremskynde tømningen af maven og dermed muliggøre en hurtig og individuelt mindre spredende resorption.
Ved indgivelse af kontrastmidlet og en tilstrækkelig stor mængde base/puffer til både at neutralisere maveindholdet og kontrastmiddel syren undgås den ved surt maveindhold sædvanlige lukning af maveporten. Udtømningen af maveindholdet med kontrastmidlet i tarmen kan ske hurtigt og uhindret, hvilket også medfører den hurtige kontrastmiddelresorption.
Med røntgenkontrastmidlerne ifølge opfindelsen muliggøres en kontrastrig fremstilling af galdeblære og galdeveje på én gang og til et nøjagtig definerbart tidspunkt. Desuden opnås fremstillingen af galdevejene allerede ved anvendelse af enkeltdosisen (^3 g skyggegivende stof).
147671 4 I midlerne ifølge opfindelsen egner sig som skyggegivende stoffer de virksomme stoffer i alle oralt anvendelige røntgenkontrastmidler specielt til cholecystocholangiografien.
Stofferne kan anvendes i form af deres salte og/eller deres syrer. Eksempelvis skal nævnes: ravsyre-mono-2,4,6-trijod-3-methylamino-N-ethyl= anilid (iosumetsyre), 2-(3-amino-2,4,6-trijodbenzyl)-smørsyre (iopan= syre), natriumsaltet af 2-(3-butyramid-2,4,6-trijodbenzyl)-smørsyre (Na-tyropanoat), natriumsaltet af β-[3-(dimethylaminomethylenairino) -2, 4,6-trijodphenyl]-propionsyre (Na-iopodat), N-(3-amino-2,4,6-trijod= benzoyl)-N-phenyl-3-aminopropionsyre (iobenzaminsyre) og natriumsaltet af a-ethyl-β-(2-[3-acetamid-2,4,6-tr ijodphenoxy]-ethoxy)-propion= syre (Na-iopronat).
Som fysiologisk acceptabel base/puffer kommer saltene af svage syrer og stærke baser i betragtning, f.eks. kombinationen af følgende ioner:
Li + , Na+, K+, Mg2+, Ca2+ og , HCOj-, CH3CCO“, PC>43“, HPC>42“, H2P04", tromethamin (trishydroxymethylaminomethan), ethanolamin og methylglu= kamin. Særligt egnede er carbonater og hydrogencarbonater som f.eks. NaHC03, MgCC'3 og Na2CC3·
Den fysiologisk acceptable base/puffer anvendes i en tilstrækkelig mængde til at neutralisere maveindholdet fuldstændigt og eventuelt give kationen til kontrastmiddelsyren. Pr. dosis skyggegivende stof (ca. 3-10 g) tilsættes ca. 0,5 - ca. 10 g, fortrinsvis 3-6 g puffer.
Med 3-4 g NaHC03 og samtidig indgivelse af 3 g kontrastmiddelsyre opnås f.eks. meget gode resultater.
Af den medfølgende tegning ses, at der med iosumetsyre og calcium= iopodat ved samtidig indgivelse af baser muliggøres en acceleret og mere kontrastrig fremstilling af galdevejene.
Fremstillingen af de hidtil ukendte orale røntgenkontrastmidler sker ved hjælp af for fagfolk almindeligt kendte metoder, f.eks. ved at man blander skyggegivende stoffer med en fysiologisk acceptabel base/ puffer eller pufferblanding med de sædvanlige galeniske hjælpestoffer, eller at man forarbejder det skyggegivende stof og den fysiologisk acceptable base/puffer eller pufferblanding hver for sig med de sædvanlige galeniske hjælpestoffer og overfører i den til sidst ønskede applikationsform.
5 T47671
Som hjælpestoffer skal f.eks. anføres: saccharose, højdispers silici= umdioxid, polyoxyethylenpolyoxypropylenpolymere, stivelse, magnesium= stéarat, natriumlaurylsulfat, talkum, sukker, silikater, cellulose, methylcellulose og polyvinylpyrrolidon.
Til applikationen egner sig de i den galeniske farmaci sædvanlige applikationsformer som f.eks. suspensioner, drageer, tabletter, kapsler og pulvere.
Ved anvendelse af midlet ifølge opfindelsen kan der opnås egenskaber, som man ikke tidligere har kunnet garantere med et kendt oralt rønt-genkontrastmiddel.
Eksempel 1 (Et pulvers sammensætning) a) Rav syr e-mono-2,^,6-tri jod-3-methylamino- N-ethylanilid, mikrofindelt 3>000 g
Saccharose *f,895 g
Polyoxyethylenpolyoxypropylenpolymere 0,100 g
Aromastoffer 0,005 g 8,000 g b) NaHCO^ som pulver eller som tabletter 3>000 g
Eksempel 2 (Et pulvers sammensætning) a) Ravsyre-mono-2,*f,6-trijod-3-methylamino- N_ethylanilid/trishydrojQmethylamincmethan 3,580 g
Saccharose *1,895 g
Polyoxyethylenpolyoxypropylenpolymere 0,100 g
Aromastoffer 0,005 g 8,580 g b) NaHCO^ som pulver eller som tabletter 2,500 g 147671 6
Eksempel 3 (Et pulvers sammensætning)
Rav syr e-mono- 2,1+,6-trijod- 3-methylamino- N-ethylanilid mikrofindelt 3,000 g
NaHCO^ <0,3 mm 3,000 g
Saccharose 5-,895 g
Polyoxyethylenpolyoxypropylenpolymere 0,100 g
Aromastoffer 0,005 g 11,000 g
Eksempel 5- (Et pulvers sammensætning)
Ravsyre-mono-2, 5-, 6-trijod-3-methylamino- N-ethylanilid/trishydroxyirethylainincinethan 3,580 g
NaHCO^ <0,3 mm 2,500 g
Saccharose 5-,895 g
Polyoxyethylenpolyoxypropylenpolymere 0,100 g
Aromastoffer 0,005 g
Eksempel 5 (En tablets sammensætning) a) Ravsyre-mono-2,5-,6-tri;]od-3-methylamino- N-ethylanilid 500,0 mg
Magnesiumstearat 3?0 mg Højdispers Si02 3j0 mg
Cellulose 100,0 mg
Lactose 95-,0 mg 700,0 mg b) RaHCO^ som tabletter 500,0 mg 6 tabletter pr. dosis.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2505218 | 1975-02-05 | ||
| DE19752505218 DE2505218A1 (de) | 1975-02-05 | 1975-02-05 | Neue orale roentgenkontrastmittel und verfahren zu ihrer herstellung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK47576A DK47576A (da) | 1976-08-06 |
| DK147671B true DK147671B (da) | 1984-11-12 |
| DK147671C DK147671C (da) | 1985-05-28 |
Family
ID=5938374
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK47576A DK147671C (da) | 1975-02-05 | 1976-02-05 | Oralt roentgenkontrastmiddel |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4101647A (da) |
| JP (1) | JPS51104020A (da) |
| AT (1) | AT355202B (da) |
| BE (1) | BE838293A (da) |
| CH (1) | CH630262A5 (da) |
| DE (1) | DE2505218A1 (da) |
| DK (1) | DK147671C (da) |
| FR (1) | FR2299854A1 (da) |
| GB (1) | GB1542677A (da) |
| IE (1) | IE42950B1 (da) |
| IT (1) | IT1055049B (da) |
| LU (1) | LU74303A1 (da) |
| NL (1) | NL7601051A (da) |
| NO (1) | NO146045C (da) |
| SE (1) | SE436686B (da) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1193761B (it) * | 1978-07-04 | 1988-08-24 | Nyegaard & Co As | Procedimento per preparare una soluzione sterile stabile di un agente di cotrasto per raggi x |
| DE3064989D1 (en) * | 1979-02-19 | 1983-11-03 | Chemie Linz Ag | A liquid composition for use in rapid oral cholecystography and process for preparing it |
| US4455292A (en) * | 1982-04-05 | 1984-06-19 | Board Of Regents, The University Of Texas System | Radiological contrast composition and methods |
| US4405575A (en) * | 1982-04-23 | 1983-09-20 | Henderson Albert E | Method of defluorinating phosphates |
| US5948387A (en) * | 1990-06-01 | 1999-09-07 | Imarx Pharmaceutical Corp. | Contrast media for ultrasonic imaging |
| US5420176A (en) * | 1990-06-01 | 1995-05-30 | Imarx Pharmaceutical Corp. | Contrast media for ultrasonic imaging |
| AU650466B2 (en) * | 1990-06-01 | 1994-06-23 | Evan C. Unger | Contrast media for ultrasonic imaging |
| DE4316722A1 (de) * | 1993-05-19 | 1994-11-24 | Fresenius Ag | Parenteral verabreichbare, unter Hitzesterilisationsbedingungen stabile O/W-Emulsion eines Röntgenkontrastmittels |
| IT1316031B1 (it) * | 2000-12-19 | 2003-03-26 | Trelleborg Wheel Systems S P A | Procedimento per radiografare i tessuti di rinforzo tessili neipneumatici e nei manufatti in genere realizzati con detti tessuti. |
| US20050255175A1 (en) * | 2004-05-17 | 2005-11-17 | Burgess W P | Method for protecting nephron against injury caused by disruption of a chemical environment in the kidneys |
| US20050255176A1 (en) * | 2004-05-17 | 2005-11-17 | Burgess W P | Method for attenuating free radical formation resulting from bodily insult |
| US7019035B2 (en) * | 2004-05-17 | 2006-03-28 | Md Scientific Llc | Method for attenuating free radical formation resulting from bodily insult |
| US7625586B2 (en) * | 2004-10-28 | 2009-12-01 | Md Scientific, Llc | Method for mitigating injury to a kidney resulting from an ischemic event |
| EP2825064A1 (en) * | 2012-03-15 | 2015-01-21 | Fresenius Kabi Deutschland GmbH | Compositions for dysphagia assessment |
| US9827265B1 (en) | 2012-04-06 | 2017-11-28 | Md Scientific, Llc | Method for attenuating free radical formation resulting from a bodily insult |
| ES2683154T3 (es) * | 2013-12-04 | 2018-09-25 | Hovione Scientia Limited | Medios de contraste que contienen formulaciones de enmascaramiento del sabor |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2940996A (en) * | 1960-06-14 | M-hocbhxchzch | ||
| US2307189A (en) * | 1940-03-02 | 1943-01-05 | Bell William | X-ray contrast composition |
| US2659690A (en) * | 1950-06-08 | 1953-11-17 | Elmer H Slaybaugh | Effervescent barium sulfate-pectin x-ray contrast composition |
| US2996433A (en) * | 1958-09-11 | 1961-08-15 | Sterling Drug Inc | Radiopaque formulations |
| US3359278A (en) * | 1963-05-24 | 1967-12-19 | Mallinckrodt Chemical Works | Nu-substituted-2, 4, 6-triiodoanilic acids and salts thereof |
| FR1437666A (fr) * | 1965-03-25 | 1966-05-06 | Schering Ag | Forme d'application pour agents de contraste radiologiques administrés par voie perorale |
| CH483261A (de) * | 1967-05-29 | 1969-12-31 | Bracco Ind Chimica Spa | Neue Röntgenkontrastmittel und Verfahren zu ihrer Herstellung |
| GB1268188A (en) * | 1968-06-11 | 1972-03-22 | Nyegaard & Co As | N-hydroxyalkyl-2,4,6-triiodosuccinanilic acids and their use as x-ray contrast agents |
-
1975
- 1975-02-05 DE DE19752505218 patent/DE2505218A1/de not_active Withdrawn
-
1976
- 1976-01-26 US US05/652,333 patent/US4101647A/en not_active Expired - Lifetime
- 1976-01-29 CH CH113476A patent/CH630262A5/de not_active IP Right Cessation
- 1976-02-02 IT IT19799/76A patent/IT1055049B/it active
- 1976-02-02 NL NL7601051A patent/NL7601051A/xx unknown
- 1976-02-03 LU LU74303A patent/LU74303A1/xx unknown
- 1976-02-03 GB GB764181A patent/GB1542677A/en not_active Expired
- 1976-02-04 JP JP51011182A patent/JPS51104020A/ja active Pending
- 1976-02-04 NO NO760367A patent/NO146045C/no unknown
- 1976-02-04 AT AT78176A patent/AT355202B/de not_active IP Right Cessation
- 1976-02-04 SE SE7601197A patent/SE436686B/xx unknown
- 1976-02-04 IE IE221/76A patent/IE42950B1/en unknown
- 1976-02-05 DK DK47576A patent/DK147671C/da not_active IP Right Cessation
- 1976-02-05 FR FR7603166A patent/FR2299854A1/fr active Granted
- 1976-02-05 BE BE164112A patent/BE838293A/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH630262A5 (de) | 1982-06-15 |
| DK147671C (da) | 1985-05-28 |
| IE42950B1 (en) | 1980-11-19 |
| NO146045B (no) | 1982-04-13 |
| IE42950L (en) | 1976-08-05 |
| FR2299854B1 (da) | 1978-08-18 |
| BE838293A (fr) | 1976-08-05 |
| DE2505218A1 (de) | 1976-08-19 |
| LU74303A1 (da) | 1976-06-18 |
| GB1542677A (en) | 1979-03-21 |
| DK47576A (da) | 1976-08-06 |
| ATA78176A (de) | 1979-07-15 |
| NO760367L (da) | 1976-08-06 |
| NO146045C (no) | 1982-08-04 |
| FR2299854A1 (fr) | 1976-09-03 |
| SE436686B (sv) | 1985-01-21 |
| US4101647A (en) | 1978-07-18 |
| IT1055049B (it) | 1981-12-21 |
| JPS51104020A (da) | 1976-09-14 |
| AT355202B (de) | 1980-02-25 |
| SE7601197L (sv) | 1976-08-06 |
| NL7601051A (nl) | 1976-08-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |