Polymeric treatment compositions

• US 9,937,201 B2
• Filed: 04/29/2016
• Issued: 04/10/2018
• Est. Priority Date: 06/14/2012
• Status: Active Grant

• Current Assignee: Microvention Incorporated (Terumo Corporation)
• Original Assignee: Microvention Incorporated (Terumo Corporation)
• Inventors: Cruise, Gregory M., Constant, Michael J., Garretson, Joshua
• Primary Examiner(s): Song, Jianfeng
• Application Number:
  US15/142,395
• Publication Number:
  US 20160243157A1
• Time in Patent Office: 711 Days
• Field of Search: None
• CPC Class Codes: A61K 31/78 of acrylic acid or derivatives thereof
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 24/0089 containing inorganic fillers not covered by groups A61L24/0078 or A61L24/0084
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Compositions are described comprising a polymer; a non-physiological pH solution; and a visualization agent; wherein the 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 delivering a composition comprising:

injecting through a delivery device into a location with physiological pH environment a liquid embolic composition comprising a biocompatible polymer, an aqueous solution with a non-physiological pH, and a visualization agent, wherein the visualization agent is an iodinated compound, barium sulfate tantalum, superparamagnetic iron oxide, gadolinium molecules, or a combination thereof,

wherein the biocompatible polymer is soluble in the aqueous solution and precipitates when it reaches the physiological pH and wherein the biocompatible polymer comprises;

a first monomer selected from a group consisting of aminopropyl methacrylamide, aminoethyl methacrylamide, N-(3-methylphridine)acrylamide, N-(2-(4-aminophenyl)ethylacrylamide, N-(4-aminobenzyl)acrylamide, N-(2-4-imidazolyl)ethyl)acrylamide, and combinations thereof; and

a second monomer selected from a group consisting of t-butyl acrylate, t-butyl acrylamide, n-octyl methacrylate, methyl methacrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, derivatives thereof, or combinations thereof.

2. The method of claim 1, wherein the visualization agent is a particulate.

3. The method of claim 1, wherein the visualization agent has a concentration of about 5% to about 65%.

4. The method of claim 1, wherein the biocompatible polymer is a reaction product of three different monomers.

5. The method of claim 1, wherein the aqueous solution with a non-physiological pH is water.

6. The method of claim 1, wherein the non-physiological pH solution has a pH of less than about 5.

7. The method of claim 1, wherein the non-physiological pH solution has a pH of greater than about 8.

8. The method of claim 1, wherein the biocompatible polymer has a concentration of about 1% w/w to about 35% w/w.

9. A method of treating a vascular disorder comprising

providing a liquid embolic composition comprising a biocompatible polymer, an aqueous solution with a non-physiological pH, and a visualization agent, wherein the visualization agent is an iodinated compound, barium sulfate tantalum, superparamagnetic iron oxide, gadolinium molecules, or a combination thereof and the biocompatible polymer is soluble in the aqueous solution and insoluble in a physiological pH and comprises:

a first monomer selected from a group consisting of aminopropyl methacrylamide, aminoethyl methacrylamide, N-(3-methylphridine)acrylamide, N-(2-(4-aminophenyl)ethylacrylamide, N-(4-aminobenzyl)acrylamide, N-(2-4-imidazolyl)ethyl)acrylamide, and combinations thereof; and

a second monomer selected from a group consisting of t-butyl acrylate, t-butyl acrylamide, n-octyl methacrylate, methyl methacrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, derivatives thereof, or combinations thereof;

inserting a delivery device into a vessel;

guiding the delivery device to an area in need of treatment wherein the area has a physiological pH;

injecting the liquid embolic polymer composition through the delivery device into the vessel at the area in need of treatment thereby immediately precipitating the biocompatible polymer and forming a solid polymeric mass; and

treating the vascular condition.

10. The method of claim 9, wherein the visualization agent is a particulate.

11. The method of claim 9, wherein the visualization agent has a concentration of about 5% to about 65%.

12. The method of claim 9, wherein the biocompatible polymer is a reaction product of three different monomers.

13. The method of claim 9, wherein the aqueous solution with a non-physiological pH is water.

14. The method of claim 9, wherein the non-physiological pH solution has a pH of less than about 5.

15. The method of claim 9, wherein the non-physiological pH solution has a pH of greater than about 8.

16. The method of claim 9, wherein the biocompatible polymer has a concentration of about 1% w/w to about 35% w/w.