Inherently radiopaque polymeric products for embolotherapy

Patent metadata

Field	Value
Publication number	US-2019142863-A1
Application number	US-201916244746-A
Country	US
Kind code	A1
Filing date	Jan 10, 2019
Priority date	Sep 25, 2003
Publication date	May 16, 2019
Grant date	—

Abstract

Preferred embodiments relate to compositions of inherently radiopaque, biocompatible, bioresorbable polymeric particles and methods of using them for embolizing a body lumen.

First claim

What is claimed is:

1 . An embolotherapy product, comprising a particulate formulation comprising a biocompatible, bioresorbable polymer, and optionally including stereoisomers thereof, wherein the polymer comprises a sufficient number of halogen atoms to render the embolotherapy product inherently radiopaque, wherein said polymer comprises one or more units described by Formula (II):

wherein X for each polymer unit is independently Br or I, Y is between 1 and 4, inclusive and R 4 is an alkyl, aryl or alkylaryl group with up to 18 carbon atoms and from 0 to 8 heteroatoms selected from O and N.

2 . The embolotherapy product of claim 1 , wherein all X groups are ortho-directed and Y is 1 or 2

3 . The embolotherapy product of claim 1 , wherein R 4 is an alkyl group.

4 . The embolotherapy product of claim 3 , wherein R 4 has the structure:

wherein R 9 for each unit is independently an alkyl, aryl or alkylaryl group containing up to 18 carbon atoms and from 0 to 8 heteroatoms selected from O and N; and R 5 and R 6 are each independently selected from hydrogen and alkyl groups having up to 18 carbon atoms and from 0 to 8 heteroatoms selected from O and N.

5 . The embolotherapy product of claim 4 , wherein R 9 for at least one unit comprises a pendant —COOR 1 group, wherein, for each unit in which it is present, the subgroup R 1 is independently a hydrogen or an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N.

6 . The embolotherapy product of claim 4 , wherein each R 9 independently has the structure:

wherein R 7 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -)a, wherein R 8 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -)n, wherein a and n are independently between 0 and 8 inclusive; and J 1 and J 2 are independently Br or I; and Q is selected from the group consisting of hydrogen, a free carboxylic acid group, and carboxylic acid esters and amides, wherein said esters and amides are selected from the group consisting of esters and amides of alkyl and alkylaryl groups containing up to 18 carbon atoms and esters and amides of biologically and pharmaceutically active compounds.

7 . The embolotherapy product of claim 4 , wherein each R 9 independently has the structure:

wherein Rya is an alkyl group containing up to 18 carbon atoms and from 0 to 5 heteroatoms selected from O and N; and wherein m is an integer from 1 to 8 inclusive; and R 1 is independently a hydrogen or an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N.

8 . The embolotherapy product of claim 4 , wherein each R 9 independently has the structure:

wherein j and m are independently an integer from 1 to 8, inclusive, and R 1 is independently a hydrogen or an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N.

9 . The embolotherapy product of claim 1 , wherein said polymer is copolymerized with a poly(C 1 -C 4 alkylene glycol).

10 . The embolotherapy product of claim 9 , wherein said poly(C 1 -C 4 alkylene glycol) is present in a weight fraction of less than about 75 wt %.

11 . The embolotherapy product of claim 10 , wherein said poly(alkylene glycol) is poly(ethylene glycol).

12 . The embolotherapy product of claim 9 , wherein between about 0.01 and about 0.99 percent of said polymer units comprise a pendant —COOH group.

13 . The embolotherapy product of claim 1 , wherein R 4 is an aryl or alkylaryl group.

14 . The embolotherapy product of claim 13 , wherein the R 4 aryl or alkylaryl group is selected so that the polymer units are diphenols.

15 . An embolotherapy product, comprising a particulate formulation comprising a biocompatible, bioresorbable polymer, and optionally including stereoisomers thereof, wherein the polymer comprises a sufficient number of halogen atoms to render the embolotherapy product inherently radiopaque, wherein said polymer comprises one or more units described by Formula (III):

wherein X for each polymer unit is independently Br or I, Y1 and Y2 are each independently between 0 and 4, inclusive, Y1+Y2 for each unit is independently between 1 and 8, inclusive, and R 2 for each polymer unit is independently an alkyl, aryl or alkylaryl group containing up to 18 carbon atoms and from 0 to 8 heteroatoms selected from O and N.

16 . The embolotherapy product of claim 15 , wherein all X groups are ortho-directed.

17 . The embolotherapy product of claim 15 , wherein Y1 and Y2 are independently 2 or less, and Y1+Y2=1, 2, 3 or 4.

18 . The embolotherapy product of claim 15 , wherein R 2 for at least one unit comprises a pendant —COOR 1 group, wherein, for each unit in which said —COOR 1 group is present, the subgroup R 1 is independently a hydrogen or an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N.

19 . The embolotherapy product of claim 15 , wherein each R 2 independently has the structure:

wherein R 7 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -)a, wherein R 8 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -)n, wherein a and n are independently between 0 and 8 inclusive; and J 1 and J 2 are independently Br or I; and Q is selected from the group consisting of hydrogen, a free carboxylic acid group, and carboxylic acid esters and amides, wherein said esters and amides are selected from the group consisting of esters and amides of alkyl and alkylaryl groups containing up to 18 carbon atoms and esters and amides of biologically and pharmaceutically active compounds.

20 . The embolotherapy product of claim 15 , wherein each R 2 independently has the structure:

wherein R 5a is an alkyl group containing up to 18 carbon atoms and from 0 to 5 heteroatoms selected from O and N; and wherein m is an integer from 1 to 8 inclusive; and R 1 is independently a hydrogen or an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N.

21 . The embolotherapy product of claim 15 , wherein each R 2 independently has the structure:

wherein j and m are independently an integer from 1 to 8, inclusive, and R 1 is independently a hydrogen or an alkyl group ranging from 1 to about 18 carbon atoms containing from 0 to 5 heteroatoms selected from O and N.

22 . The

Assignees

• Univ Rutgers

Inventors

• Brandom Donald K
• Schmid Eric
• Zeltinger Joan
• Bolikal Durgadas
• Kohn Joachim B

Classifications

• A61K49/0442

  Polymeric X-ray contrast-enhancing agent comprising a halogenated group · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title