Radio-opaque polymeric compositions

• US 6,599,448 B1
• Filed: 05/10/2000
• Issued: 07/29/2003
• Est. Priority Date: 05/10/2000
• Status: Active Grant

• Current Assignee: Hydromer, Inc.
• Original Assignee: Hydromer, Inc.
• Inventors: Ehrhard, Joseph A. Jr., Hennessey, Patrick
• Primary Examiner(s): TUCKER, PHILIP C
• Application Number:
  US09/568,115
• Time in Patent Office: 1,175 Days
• Field of Search: 424/9.45, 424/9.451, 424/9.4, 424/9.43, 252/582, 252/408.1, 252/583
• US Class Current: 252/582
• CPC Class Codes: A61K 49/0442 Polymeric X-ray contrast-enhancing agent comprising a halogenated group
• CPC Class Codes: C08F 8/00 Chemical modification by after-treatment graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C
• CPC Class Codes: C09D 5/32 Radiation-absorbing paints protection against X-, gamma- or corpuscular radiation G21F

Abstract

The present invention provides a radio-opaque composition including a polymer or monomer, wherein the polymer or monomer has a non-leachable radio-opaque moiety. The non-leachable radio-opaque moiety is covalently attached to the polymer or monomer.

Claims

1. A radio-opaque composition comprising a polymer or monomer, and an antithrombotic, wherein said polymer or monomer has a non-leachable radio-opaque moiety, wherein said non-leachable radio-opaque moiety is covalently attached to said polymer or said monomer, and wherein said antithrombotic agent is releasable or non-releasable from said composition.

3. The radio-opaque composition of claim 1, wherein said polymer is a natural polymer or a synthetic polymer or a combination thereof;

wherein said synthetic polymer is a polymer blend, alloy, random copolymer, block copolymer, graft copolymer or homopolymer; and

wherein said synthetic polymer comprises poly(vinyl alcohol), poly(vinylpyrrolidone), poly(caprolactone), poly(hydroxybutarates), poly(caprolactams), poly(terephthalate), poly(vinyl chloride), poly(propylene), poly(ethylene oxide), poly(propylene oxide), poly(styrene), poly(ethylene), poly(urethanes), silicone elastomers or combinations thereof;

wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride;

wherein said polymer or said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride or a carboxylic acid; and

wherein said non-leachable radio-opaque moiety is covalently attached to said polymer or said monomer.

2. A radio-opaque primer comprising a monomer, wherein said monomer has a non-leachable radio-opaque moiety, wherein said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an ester, an aldehyde, an N-hydroxysuccinimide ester, an epoxide, a carboxylic ester, a tresylate, an anhydride, an alkyl halide, a carboxylic acid, a haloketone, an alkene, an alkyne or an acyl chloride;

and wherein said monomer is covalently attached to an object by a covalent linkage.

4. A radio-opaque primer of claim 2, wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride.

9. A composition according to claim 2 wherein said radio-opaque moiety is an amidotrizoate, an iothalamate, an iohexol, an iopamidol, an iopromide, ioxaglic acid, an iopadate, an iotroxate or an ioxaglate.

5. A radio-opaque composition comprising:

(a) a polymer or monomer, wherein said polymer or monomer has a non-leachable radio-opaque moiety, and

(b) a polyvinylpyrrolidone-polyurethane complex, wherein said polymer is a natural polymer or a synthetic polymer or a combination thereof;

wherein said synthetic polymer is a polymer blend, alloy, random copolymer, block copolymer, graft copolymer or homopolymer;

wherein said synthetic polymer comprises poly(vinyl alcohol), poly(vinylpyrrolidone), poly(caprolactone), poly(hydroxybutarates), poly(caprolactams), poly(terephthalate), poly(vinyl chloride), poly(propylene), poly(ethylene oxide), poly(propylene oxide), poly(styrene), poly(ethylene), poly(urethanes), silicone elastomers or combinations thereof;

wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride; and

wherein said polymer or said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride or a carboxylic acid; and

wherein said non-leachable radio-opaque moiety is covalently attached to said polymer or said monomer.

6. A composition according to claim 5 wherein said radio-opaque moiety is a halogenated aromatic compound with a reactive functional group.

7. A composition according to claim 6 wherein said halogenated aromatic compound is an aromatic tri-iodide or an aromatic tri-bromide.

8. A composition according to claim 6 wherein said reactive functional group of said radio-opaque moiety is a hydroxyl, a carboxyl, an amine, an amide, a carbonyl, a thiol, an allyl, a vinyl or an anhydride.

10. A composition according to claim 5 wherein said radio-opaque moiety is Iobenguane, Iobenzamic Acid, Iocarmic Acid, Iocetamic Acid, Iodamide, Iodipamide, Iodixanol, Iodized Oil, Iodoalphionic Acid, p-Iodoaniline, o-Iodobenzoic Acid, Iodochlorhydroxyquin, o-Iodohippurate Sodium, o-Iodophenol, p-Iodophenol, Iodophthalein Sodium, Iodopsin, Iodopyracet, Iodopyrrole, Iodoquinol, Iofetamine ¹²³I, Ioglycamic Acid, Iohexol, Iomeglamic Acid, Iopamidol, Iopanoic acid, Iopentol, Iophendylate, Iophenoxic Acid, Iopromide, Iopronic Acid, Iopydol, Iopydone, Iothalamic Acid, Iotrolan, Ioversol, Ioxaglic Acid, Ioxilan, or Ipodate.

11. A composition according to claim 5 wherein said natural polymer is a cellulose, chitosan, chitin, starch, hyaluronic acid, chondroitin sulfate, xanthan, guar gum;

or an ether or an ester derivative thereof;

or a block, a graft or random copolymer thereof;

or a blend thereof.

12. A composition according to claim 5 wherein said radio-opaque moiety is covalently attached to said polymer or said monomer through an amine, amide, anhydride, carbamate, carbonate, carboxyl, ether, ester, imide, thiol, thiocarbamates, or urea covalent linkage.

13. A composition according to claim 5 wherein said radio-opaque moiety is covalently attached to said polymer or said monomer by the use of heat, ultraviolet irradiation, gamma irradiation, an acidic initiator, a basic initiator, a peroxide initiator, a persulfate initiator or an azo initiator.

14. A composition according to claim 5 further comprising at least one additional ingredient wherein said additional ingredient is releasable or non-releasable from said composition.

15. A composition according to claim 14 wherein said additional ingredient is a biologically active material.

16. A composition according to claim 15 wherein said biologically active material is a biostatic agent, a cytostatic agent, a radiation emitter, a biomolecule, an anti-inflammatory agent, an immunosuppressant or an antiseptic.

17. A composition according to claim 15 wherein said biologically active material is an antibiotic.

18. A composition according to claim 15 wherein said biologically active material is an antithrombotic agent.

19. A composition according to claim 5 wherein said composition has a low coefficient of friction when wetted with water or a water-containing substance.

20. A composition according to claim 5 further comprising a solvent.

21. A composition according to claim 20 wherein said covalent linkage is formed as said solvent is removed.

22. A composition according to claim 5 wherein said covalent linkage is formed during formulation of said composition.

23. A composition according to claim 5 wherein said composition is a covering composition.

24. A covering composition according to claim 23 wherein said covering composition is a coating.

25. A covering composition according to claim 23 wherein said covering composition is a primer.

26. A composition according to claim 25 wherein said primer is a blend of said monomers.

27. A primer according to claim 25 wherein said monomer is covalently attached to an object by a covalent linkage.

28. A primer according to claim 25 wherein said monomer adheres to an object.

29. A radio-opaque primer comprising a monomer which is covalently attached to a non-leachable radio-opaque moiety, wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride;

and wherein said monomer has at least one reactive functional group selected from the group consisting of an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride and a carboxylic acid;

wherein said monomer adheres to an object.

30. A medical device covered with a composition comprising:

(a) a polymer or a monomer wherein said polymer or said monomer has a non-leachable radio-opaque moiety, and

(b) a polyvinylpyrrolidone-polyurethane complex, wherein said radio-opaque moiety is a halogenated aromatic compound with a reactive functional group;

wherein said polymer is a natural polymer or a synthetic polymer or a combination thereof, wherein said synthetic polymer is a polymer blend, alloy, random copolymer, block copolymer, graft copolymer or homopolymer;

wherein said synthetic polymer comprises poly(vinyl alcohol), poly(vinylpyrrolidone), poly(caprolactone), poly(hydroxybutarates), poly(caprolactams), poly(terephthalate), poly(vinyl chloride), poly(propylene), poly(ethylene oxide), poly(propylene oxide), poly(styrene), poly(ethylene), poly(urethanes), silicone elastomers or combinations thereof;

wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride; and

wherein said polymer or said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride, or a carboxylic acid.

31. A medical device according to claim 30 wherein said medical device is a catheter, guide wire, shunt, screw, pin, prosthesis, plate, film, sponge, suture, tube, cannula, balloon, needle, marker or stylet.

32. A stent covered with a composition comprising:

(a) a polymer or a monomer wherein said polymer or said monomer has a non-leachable radio-opaque moiety, and

(b) a polyvinylpyrrolidone-polyurethane complex, wherein said radio-opaque moiety is a halogenated aromatic compound with a reactive functional group;

wherein said polymer is a natural polymer or a synthetic polymer or a combination thereof;

wherein said synthetic polymer is a polymer blend, alloy, random copolymer, block copolymer, graft copolymer or homopolymer;

wherein said synthetic polymer comprises poly(vinyl alcohol), poly(vinylpyrrolidone), poly(caprolactone), poly(hydroxybutarates), poly(caprolactams), poly(terephthalate), poly(vinyl chloride), poly(propylene), poly(ethylene oxide), poly(propylene oxide), poly(styrene), poly(ethylene), poly(urethanes), silicone elastomers or combinations thereof;

wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride; and

wherein said polymer or said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride, or a carboxylic acid.

33. A method of rendering an object radio-opaque comprising:

applying a composition to said object, wherein said composition comprises;

(a) a polymer or monomer wherein said polymer or said monomer has a non-leachable radio-opaque moiety, and

(b) a polyvinylpyrrolidone-polyurethane complex, wherein said polymer is a natural polymer or a synthetic polymer or a combination thereof, wherein said synthetic polymer is a polymer blend, alloy, random copolymer, block copolymer, graft copolymer or homopolymer, wherein said synthetic polymer comprises poly(vinyl alcohol), poly(vinylpyrrolidone), poly(caprolactone), poly(acrylamides), poly(hydroxybutarates), poly(caprolactams), poly(terephthalate), poly(vinyl chloride), poly(propylene), poly(ethylene oxide), poly(acrylic acid), poly(propylene oxide), poly(styrene), poly(ethylene), poly(urethanes), silicone elastomers or combinations thereof;

wherein said monomer is an acrylate, allyllic compound, amide, amine, anhydride, epoxide, isocyanate, methacrylate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride; and

wherein said polymer or said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride or a carboxylic acid.

34. A method of rendering an object radio-opaque comprising:

applying a radio-opaque primer to said object, wherein said primer comprises a monomer, wherein said monomer has a non-leachable radio-opaque moiety, wherein said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an ester, an aldehyde, an N-hydroxysuccinimide ester, an epoxide, a carboxylic ester, a tresylate, an anhydride, an alkyl halide, a carboxylic acid, a haloketone, an alkene, an alkyne or an acyl chloride; and

wherein said monomer is covalently attached to an object by a covalent linkage.

35. A method of rendering an object radio-opaque comprising:

applying a primer to said object, wherein said primer comprises a monomer which is covalently attached to a non-leachable radio-opaque moiety, and a a polyvinylpyrrolidone-polyurethane complex;

wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride; and

wherein said monomer has at least one reactive functional group selected from the group consisting of an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride and a carboxylic acid;

wherein said monomer adheres to an object.

36. An object covered with a composition comprising:

(a) a polymer or monomer, wherein said polymer or monomer has a non-leachable radio-opaque moiety, and

(b) a polyvinylpyrrolidone-polyurethane complex, wherein said polymer is a natural polymer or a synthetic polymer or a combination thereof;

wherein said synthetic polymer is a polymer blend, alloy, random copolymer, block copolymer, graft copolymer or homopolymer;

wherein said synthetic polymer comprises poly(vinyl alcohol), poly(vinylpyrrolidone), poly(caprolactone), poly(hydroxybutarates), poly(caprolactams), poly(terephthalate), poly(vinyl chloride), poly(propylene), poly(ethylene oxide), poly(propylene oxide), poly(styrene), poly(ethylene), poly(urethanes), silicone elastomers or combinations thereof;

wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride; and

wherein said polymer or said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride or a carboxylic acid; and

wherein said non-leachable radio-opaque moiety is covalently attached to said polymer or said monomer.

37. An object covered with a primer comprising:

wherein said primer comprises a monomer, wherein said monomer has a non-leachable radio-opaque moiety, wherein said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an ester, an aldehyde, an N-hydroxysuccinimide ester, an epoxide, a carboxylic ester, a tresylate, an anhydride, an alkyl halide, a carboxylic acid, a haloketone, an alkene, an alkyne or an acyl chloride; and

wherein said monomer is covalently attached to said object by a covalent linkage.

38. An object covered with a primer comprising:

wherein said primer comprises a monomer and a polyvinylpyrrolidone-polyurethane complex;

wherein said monomer has a non-leachable radio-opaque moiety, wherein said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an ester, an aldehyde, an N-hydroxysuccinimide ester, an epoxide, a carboxylic ester, a tresylate, an anhydride, an alkyl halide, a carboxylic acid, a haloketone, an alkene, an alkyne or an acyl chloride; and

wherein said monomer adheres to said object.

39. A radio-opaque covering composition comprising:

(a) a polymer or monomer, wherein said polymer or monomer has a non-leachable radio-opaque moiety, and

(b) an aqueous coating solution comprising a blend of a polyacrylate and a poly(ethylene oxide), wherein said polymer is a natural polymer or a synthetic polymer or a combination thereof;

wherein said synthetic polymer is a polymer blend, alloy, random copolymer, block copolymer, graft copolymer or homopolymer;

wherein said synthetic polymer comprises poly(vinyl alcohol), poly(vinylpyrrolidone), poly(caprolactone), poly(hydroxybutarates), poly(caprolactams), poly(terephthalate), poly(vinyl chloride), poly(propylene), poly(ethylene oxide), poly(propylene oxide), poly(styrene), poly(ethylene), poly(urethanes), silicone elastomers or combinations thereof;

wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride; and

wherein said polymer or said monomer has at least one reactive functional group, wherein said reactive fuinctional group is an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride or a carboxylic acid;

wherein said non-leachable radio-opaque moiety is covalently attached to said polymer or said monomer.

40. A radio-opaque covering composition comprising:

a) a polymer or monomer, wherein said polymer or monomer has a non-leachable radio-opaque moiety, and

(b) a block copolymer of a dimethylacrylamide and glycidyl methacrylate, wherein said polymer is a natural polymer or a synthetic polymer or a combination thereof;

wherein said synthetic polymer is a polymer blend, alloy, random copolymer, block copolymer, graft copolymer or homopolymer;

wherein said synthetic polymer comprises poly(vinyl alcohol), poly(vinylpyrrolidone), poly(caprolactone), poly(hydroxybutarates), poly(caprolactams), poly(terephthalate), poly(vinyl chloride), poly(propylene), poly(ethylene oxide), poly(propylene oxide), poly(styrene), poly(ethylene), poly(urethanes), silicone elastomers or combinations thereof;

wherein said monomer is an allyllic compound, amide, amine, anhydride, epoxide, isocyanate, silyl, thiol compound, thioisocyanate, vinyl compound, ester, acid chloride, acrolein or acryloylchoride; and

wherein said polymer or said monomer has at least one reactive functional group, wherein said reactive functional group is an isocyanate, an isothiocyanate, an epoxide, a carboxylic ester, a tresylate, an anhydride or a carboxylic acid;

wherein said non-leachable radio-opaque moiety is covalently attached to said polymer or said monomer.