Inherently radiopaque polymeric products for embolotherapy

Patent metadata

Field	Value
Publication number	US-11246884-B2
Application number	US-201916244746-A
Country	US
Kind code	B2
Filing date	Jan 10, 2019
Priority date	Sep 25, 2003
Publication date	Feb 15, 2022
Grant date	Feb 15, 2022

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 suspension product for embolizing a body lumen, comprising particles of a biocompatible, bioresorbable polymer, optionally including stereoisomers thereof, in a pharmaceutically acceptable liquid, wherein the polymer particles have an excluded diameter of about 10 microns to about 3,000 microns, wherein the embolotherapy product is radiopaque by virtue of halogen in the polymer, and wherein said polymer comprises multiple units of 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 group with up to 18 carbon atoms and from 0 to 8 heteroatoms selected from O and N, or R 4 has the structure:

wherein 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, and 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 ]](—CH 2 -) a , wherein R 8 is selected from the group consisting of —CH═CH—, —CHJ 1 -CHJ 2 - and (—CH 2 -) n [[(—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;
wherein the polymer particle shape is selected from the group consisting of spherical and geometrically non-uniform, wherein the particles are solid, hollow or porous; and
wherein said polymer is copolymerized with a poly(C 1 -C 4 alkylene glycol), which is present in a weight fraction of less than about 75 wt %.

2. The embolotherapy product of claim 1 , wherein all X groups are ortho-directed with respect to the phenolic oxygen 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 1 , wherein R 9 for at least one unit comprises a pendant —COOR 1 group, wherein, for each unit in which it is present, the sub-group 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.

5. The embolotherapy product of claim 1 , wherein each R 9 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 n 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.

6. The embolotherapy product of claim 1 , wherein each R 9 independently has the structure:

wherein a and n 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.

7. The embolotherapy product of claim 1 , wherein said poly(C 1 -C 4 alkylene glycol) is poly(ethylene glycol).

8. The embolotherapy product of claim 1 , wherein between about 0.01 and about 0.99 percent of said polymer units comprise a pendant —COOH group.

9. The embolotherapy product of claim 1 , wherein said polymer further comprises an effective amount of at least one therapeutic agent.

10. The embolotherapy product of claim 9 , wherein said at least one therapeutic agent is selected from the group consisting of a chemotherapeutic agent, a non-steroidal anti-inflammatory, or a steroidal anti-inflammatory.

11. The embolotherapy suspension product of claim 1 , further comprising an effective amount of a radiopacifying agent, selected from the group consisting of iodine, bromine, barium, bismuth, gold, platinum, tantalum, tungsten, and mixtures thereof.

Assignees

• Univ Rutgers

Inventors

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

Classifications

• A61P9/14

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

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61K31/785 Primary

  Polymers containing nitrogen · 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

• A61K49/0442

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