Polymers including active agents

Patent metadata

Field	Value
Publication number	US-10946100-B2
Application number	US-201916250878-A
Country	US
Kind code	B2
Filing date	Jan 17, 2019
Priority date	Apr 29, 2014
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

Polymers are described herein comprising: a reaction product of a prepolymer solution including at least one macromer and at least one visualization agent; and an active agent electrostatically bound to the polymer filament or chemically bound to the at least one monomer; wherein the polymer filament does not include metallic support members.

First claim

We claim:

1. A method of forming a therapeutic polymer filament comprising:
reacting a prepolymer solution including:
at least one macromer selected from ethoxylated pentaerythritol, ethoxylated trimethylolpropane, or a combination thereof,
at least one visualization agent, and
a polymerizable pharmaceutical agent having a structure

wherein R 1 is

wherein each R 2 and R 3 can independently be H, CH 3 , C 2 -C 6 alkyl, C 2 -C 6 substituted with a halogen or other C 1 -C 6 alkyl, NH 2 , CO 2 , ON, CF 3 , F, Cl, Br, I, CCl 3 , OH, or CH 2 OH;

n is 1, 2, 3, or 4;
m is 1, 2, 3, or 4;
X 1 , X 2 , X 3 , and X 4 are each N or CH; and
X 5 is O, CH 2 , or NH; and
p is 0, 1, 2, 3 or 4

thereby forming the therapeutic polymer filament wherein the polymerizable pharmaceutical agent is chemically bound to the therapeutic polymer filament.

2. The method of claim 1 , further comprising adding at least one crosslinker to the prepolymer solution, wherein the at least one crosslinker includes an ester, a carbonate, a thioester, or a combination thereof.

3. The method of claim 1 , further comprising adding at least one monomer to the prepolymer solution, wherein the at least one monomer is t-butyl acrylamide, 2-hydroxyethyl methacrylate, hydroxyl propyl acrylate, hydroxyl butylacrylate, or a combination thereof.

4. The method of claim 3 , wherein the at least one monomer has a concentration of between about 5% and about 40% w/w of the prepolymer solution.

5. The method of claim 1 , wherein the at least one macromer has a concentration of between about 15% and about 25% w/w of the prepolymer solution or has a molecular weight of between about 100 g/mole and about 5,000 g/mole.

6. The method of claim 1 , wherein the at least one visualization agent is barium, bismuth, tantalum, platinum, gold, iodine-containing molecules, barium sulfate, or a combination thereof.

7. The method of claim 1 , wherein the at least one visualization agent is an iodine-containing molecule.

8. A method of forming a therapeutic polymer filament comprising:
reacting a prepolymer solution including:
at least one macromer selected from poly(ethylene glycol), poly(propylene glycol), poly(tetramethylene oxide), ethoxylated pentaerythritol, ethoxylated trimethylolpropane, poly(vinyl alcohol), or a combination thereof, and
a polymerizable pharmaceutical agent having a structure

wherein R 1 is

wherein each R 2 and R 3 can independently be H, CH 3 , C 2 -C 6 alkyl, C 2 -C 6 substituted with a halogen or other C 1 -C 6 alkyl, NH 2 ; CO 2 , ON, CF 3 , F, Cl; Br, I, CCl 3 , OH, or CH 2 OH;

n is 1, 2, 3, or 4;
m is 1, 2, 3, or 4;
X 1 , X 2 , X 3 , and X 4 are each N or CH; and
X 5 is O, CH 2 , or NH; and
p is 0, 1, 2, 3 or 4

thereby forming the therapeutic polymer filament wherein the polymerizable pharmaceutical agent is chemically bound to the therapeutic polymer filament.

9. The method of claim 8 , further comprising adding at least one monomer to the prepolymer solution, wherein the at least one monomer is t-butyl acrylamide, 2-hydroxyethyl methacrylate, hydroxyl propyl acrylate, hydroxyl butylacrylate, or a combination thereof.

10. The method of claim 9 , wherein the at least one monomer has a concentration of between about 5% and about 40% w/w of the prepolymer solution.

11. The method of claim 8 , wherein the at least one macromer has a concentration of between about 15% and about 25% w/w of the prepolymer solution or has a molecular weight of between about 100 g/mole and about 5,000 g/mole.

12. The method of claim 8 , further comprising at least one visualization agent in the prepolymer solution.

13. The method of claim 12 , wherein the at least one visualization agent is barium, bismuth, tantalum, platinum, gold, iodine-containing molecules, barium sulfate, or a combination thereof.

14. The method of claim 12 , wherein the at least one visualization agent is an iodine-containing molecule.

15. The method of claim 8 , further comprising at least one crosslinker, wherein the at least one crosslinker includes an ester, a carbonate, a thioester, or a combination thereof.

16. A method of forming a therapeutic polymer filament comprising:
reacting a prepolymer solution including:
at least one macromer selected from polyethylene glycol), poly(propylene glycol), poly(tetramethylene oxide), ethoxylated pentaerythritol, ethoxylated trimethylolpropane, poly(vinyl alcohol), or a combination thereof, and
a polymerizable pharmaceutical agent having a structure

thereby forming the therapeutic polymer filament wherein the polymerizable pharmaceutical agent is chemically bound to the therapeutic polymer filament.

17. The method of claim 16 , further comprising adding at least one monomer to the prepolymer solution, wherein the at least one monomer is t-butyl acrylamide, 2-hydroxyethyl methacrylate, hydroxyl propyl acrylate, hydroxyl butylacrylate, or a combination thereof.

18. The method of claim 17 , wherein the at least one monomer has a concentration of between about 5% and about 40% w/w of the prepolymer solution.

19. The method of claim 16 , wherein the at least one macromer has a concentration of between about 15% and about 25% w/w of the prepolymer solution or has a molecular weight of between about 100 g/mole and about 5,000 g/mole.

20. The method of claim 16 , further comprising at least one visualization agent in the prepolymer solution.

21. The method of claim 20 , wherein the at least one visualization agent is barium, bismuth, tantalum, platinum, gold, iodine-containing molecules, barium sulfate, or a combination thereof.

22. The method of claim 20 , wherein the at least one visualization agent is an iodine-containing molecule.

23. The method of claim 16 , further comprising at least one crosslinker, wherein the at least one crosslinker includes an ester, a carbonate, a thioester, or a combination thereof.

Assignees

• Microvention Inc

Inventors

• Cruise Gregory M
• Harris Clayton G
• Constant Michael J

Classifications

• C07H19/06

  Pyrimidine radicals · CPC title

• C07F15/0093

  without a metal-carbon linkage · CPC title

• A61L31/18

  Materials at least partially X-ray or laser opaque · CPC title

• A61L2430/36

  for embolization or occlusion, e.g. vaso-occlusive compositions or devices · CPC title

• A61P35/00

  Antineoplastic agents · CPC title