Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1989-09-21
1999-03-23
Kight, John
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 51, 536124, C08B 3702, C07H 100
Patent
active
058861696
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to iodinated polymers which are usable in radiography as contrast media, and in particular as injectable contrast media.
Compounds used as injectable contrast media must not only absorb X-rays, but must also possess various properties and, in particular,
Hitherto, it was necessary to inject patients with large amounts of contrast media in order to obtain a correct diagnosis from the radiographic image. Thus, research was directed towards derivatives having more suitable osmolarity and reduced toxicity. Two new categories of media consequently appeared: ionic media having low osmolarity and non-ionic media.
More recently, an effort has been made to develop another approach, consisting in retarding the diffusion of the opacifying media in the extravascular space.
To this end, various iodinated polymers have been proposed. Thus, U.S. Pat. No. 3,852,341 describes iodinated polymers obtained by the copolymerization of a 3,5-DIACYLAMINO-2,4,6-triiodobenzene-containing acid with bifunctional compounds such as a diepoxide. These polymers are water-soluble. FR-A-2,200,018 describes related copolymers which are crosslinked and water-insoluble.
U.S. Pat. No. 4,406,878 describes an iodinated polymer which is obtained by the reaction of tetraiodophthalic anhydride with polyvinyl alcohol and crosslinking.
The present invention is directed towards the provision of new iodinated polymers which are distinguished by low osmolarity and good tolerability.
The American patent U.S. Pat. No. 2,811,516 describes an iodized polymer comprising a skeleton consisting of a dextrane onto which are grafted iodocarboxymethyl groups.
The subject of the present invention is iodinated polymers, characterized in that they comprise a skeleton consisting of a dextran onto which are grafted groups of formula ##STR1## in which A is a group forming a bridge between the dextran chain and the benzene ring, pharmaceutically acceptable base and the groups of the formulae and ##STR2## and R.sub.2 is a group chosen from the-groups of the formulae and ##STR3## in which formulae R.sub.3 and R.sub.5 are selected from C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 hydroxy-alkyl, C.sub.1 to C.sub.6 polyhydroxyalkyl, (C.sub.1 -C.sub.6) alkoxy (C.sub.1 -C.sub.6) alkyl and (C.sub.1 -C.sub.6)alkoxy (C.sub.1 -C.sub.6)hydroxyalkyl groups, C.sub.6 alkyl, C.sub.1 to C.sub.6 hydroxyalkyl, C.sub.1 to C.sub.6 polyhydroxyalkyl, (C.sub.1 -C.sub.6) alkoxy (C.sub.1 -C.sub.6) alkyl and (C.sub.1 -C.sub.6) alkoxy (C.sub.1 -C.sub.6) hydroxyalkyl groups, ##STR4## m being an integer from 1 to 6, and R.sub.1 and R.sub.2 having the meaning given above.
The dextran which acts as a support for the triiodobenzene groups is a polymer generally obtained from sucrose by the action of Leuconostoc mesenteroides.
Dextrans are polymers consisting of .alpha.-D-glucose units. The glycosyl units of the chains are linked essentially via 1.fwdarw.6 linkages according to the following diagram ##STR5##
Commercial dextrans have generally. undergone a partial hydrolysis followed by a fractionation to obtain polymers which are more homogeneous from the standpoint of molecular mass.
The dextrans used in the present invention can have, in particular, masses of 3,000 to 150,000, and preferably have masses of 10,000 to 100,000, in order to yield sufficiently water-soluble iodinated polymers.
The polymers according to the invention may be obtained by grafting a triiodobenzene unit onto the chain of a dextran.
Such grafting may be carried out: reagent such as an acid chloride or acid anhydride containing a triiodobenzene group. reactive groups, followed by reaction of these more reactive groups with a suitable triiodobenzene derivative.
In the first case, polymers containing ester groups are obtained according to the following scheme ##STR6##
The reaction is advantageously performed by prior activation of the dextran with a base such as potassium tert-butylate, sodium hydride or sodium methylate or ethylate.
The iodinated acid chloride can be, in particular, 2,4,6-triiodobenzoi
REFERENCES:
patent: 2811516 (1957-10-01), Novak
patent: 3702866 (1972-11-01), Salvesen et al.
patent: 3852341 (1974-12-01), Bjork et al.
patent: 4160015 (1979-07-01), Wiegert et al.
patent: 4406878 (1983-09-01), DeBoer
patent: 4455292 (1984-06-01), Bertoni
"X-ray contrast substance", Chemical Abstracts, 67490b, vol. 75, 1971, By N. Sviridov et al., p. 238.
Morrison & Boyd, "Organic Chemistry" published 1975 by Allyn and Bacon, Inc. (Boston), see p. 665.
Bonnemain Bruno
Doucet Didier
Meyer Dominique
Nigretto Jean-Maxime
Paris Dominique
Guerbet S.A.
Kight John
White Everett
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