Polymeric treatment compositions

• US 10,258,716 B2
• Filed: 04/19/2017
• Issued: 04/16/2019
• Est. Priority Date: 10/15/2012
• Status: Active Grant

• Current Assignee: Microvention Incorporated (Terumo Corporation)
• Original Assignee: Microvention Incorporated (Terumo Corporation)
• Inventors: Cruise, Gregory M., Constant, Michael J., Keeley, Edward Michael, Greene, Rob, Harris, Clayton
• Primary Examiner(s): Yoon, Tae H
• Application Number:
  US15/491,864
• Publication Number:
  US 20170216484A1
• Time in Patent Office: 727 Days
• Field of Search: 523105, 523117, 424 137, 424 153, 424 169
• CPC Class Codes: A61K 49/0442 Polymeric X-ray contrast-enhancing agent comprising a halogenated group
• CPC Class Codes: A61K 49/12 Macromolecular compounds
• CPC Class Codes: A61L 2300/44 Radioisotopes, radionuclides
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/06 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043, A61L24/046 take precedence
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 33/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 33/26 Homopolymers or copolymers of acrylamide or methacrylamide

Abstract

Polymeric compositions are described comprising a biocompatible polymer including a biodegradable linkage to a visualization agent and a non-physiological pH solution; wherein the biocompatible polymer is soluble in the non-physiological pH solution and insoluble at a physiological pH. Methods of forming the solutions and polymers are disclosed as well as methods of therapeutic use.

Claims

1. A method of treating a vascular disorder, the method comprising:

injecting a liquid composition including a polymer solubilized in a non-physiological solution into a vessel,

wherein the polymer precipitates when contacting a physiological solution in the vessel and forms a substantially stable polymer, wherein the polymer includes at least one monomeric unit including a biodegradable linkage to a visualization agent, and wherein substantially stable is where the polymer is greater than 90% intact after about 1 month.

2. The method of claim 1, wherein the at least one monomeric unit includes at least one aromatic ring and at least one polymerizable moiety.

3. The method of claim 1, wherein the biodegradable linkage is Seq. ID 1, Seq. ID 2, Seq. ID 3, Seq. ID 4, Seq. ID 5, Seq. ID 6, Seq. ID 7, Seq. ID 8, Seq. ID 9, Seq. ID 10, Seq. ID 11, Seq. ID 12, or Seq. ID 13.

4. The method of claim 1, wherein the biodegradable linkage is an ester or a polyester.

5. The method of claim 1, wherein the injecting is through a delivery device.

6. The method of claim 5, wherein the delivery device is a catheter.

7. The method of claim 6, wherein the delivery device is a microcatheter or a cannula.

8. The method of claim 6, wherein the delivery device is flushed with the non-physiological solution before injecting the composition.

9. The method of claim 1, wherein substantially stable is where the polymer is greater than 95% intact after about 1 month.

10. The method of claim 1, wherein substantially stable is where the polymer is greater than 60% intact after about 1 year.

11. The method of claim 1, wherein substantially stable is where the polymer is greater than 60% intact after about 5 years.

12. The method of claim 1, wherein substantially stable is where the polymer is greater than 90% intact after about 2 months.

13. The method of claim 1, wherein substantially stable is where the polymer is greater than 80% intact after about 6 months.

14. The method of claim 1, wherein the non-physiological solution is dimethyl formamide.

15. The method of claim 1, wherein the non-physiological solution is dimethyl sulfoxide.

16. The method of claim 1, wherein the polymer includes a reaction product of between about 75% and about 98% 2-oxo-2-(1-oxo-1-(1-oxo-1-(2,4,6-triiodophenoxy)propan-2-yloxy)propan-2-yloxy)ethoxy)ethyl acrylate, between about 2% and about 25% hydroxyethyl methacrylate, and less than 1% azobisisobutyronitrile.

17. The method of claim 1, wherein the polymer includes a reaction product of between about 85% and about 98% 1-((2-(methacryloyloxy)ethoxy)carbonyloxy) ethyl 3,5-diacetamido-2,4,6-triiodobenzoate, between about 2% and about 15% hydroxyethyl methacrylate, and less than 1% azobisisobutyronitrile.