Compositions containing fast-leaching plasticizers for improved performance of medical devices

• US 20060058868A1
• Filed: 09/10/2004
• Published: 03/16/2006
• Est. Priority Date: 09/10/2004
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Kleine, Klaus, Gale, David C., Atladottir, Svava Maria, Pacetti, Stephen D., Abbate, Anthony J.
• Granted Patent: US 7,229,471 B2
• Time in Patent Office: Days
• US Class Current: 623/1.150
• CPC Class Codes: A61L 31/141 Plasticizers

Abstract

Medical implants containing a temporary plasticizer, methods of producing such implants, and methods of using the implants in treating a disease, or ameliorating one or more symptoms thereof, in a subject are provided.

Claims

1. A medical article comprising

an implant comprising a polymeric material,

wherein the polymeric material comprises a plasticizing agent capable of sufficiently increasing a strain-to-failure in the polymeric material to prevent or reduce a formation of cracks in the polymeric material while placing the implant in a subject,

wherein the plasticizing agent leaches from the polymeric material after placing the implant in a subject to provide a sufficient rigidity in the polymeric material, and

wherein the plasticizing agent leaches from the polymeric material in less than an amount of time necessary for a required dimension of the implant to change substantially in response to a stress.

2. The medical article of claim 1, wherein the implant comprises an expandable component that is adapted to expand mechanically or self-expand.

3. The medical article of claim 2, wherein the expandable component is configured to expand by application of pressure from a balloon of a catheter.

4. The medical article of claim 1, wherein the implant comprises a stent or a vena cava filter.

5. The medical article of claim 4, wherein the stent is selected from a group consisting of vascular stents, renal stents, biliary stents, pulmonary stents and gastrointestinal stents.

6. The medical article of claim 1, wherein the implant comprises a biodegradable polymer.

7. The medical article of claim 1, wherein the implant comprises a polymer selected from a group consisting of polyesters, polyhydroxyalkanoates (PHAs), poly(ester amides);

amino acids;

poly(ethylene glycol) (PEG) and/or alcohol groups, polycaprolactones, poly(L-lactide), poly(D,L-lactide), poly(D,L-lactide-co-PEG) block copolymers, poly(D,L-lactide-co-trimethylene carbonate), polyglycolides, poly(lactide-co-glycolide), polydioxanones, polyorthoesters, polyanhydrides, poly(glycolic acid-co-trimethylene carbonate), polyphosphoesters, polyphosphoester urethanes, poly(amino acids), polycyanoacrylates, poly(trimethylene carbonate), poly(imino carbonate), polycarbonates, polyurethanes, copoly(ether-esters), polyalkylene oxalates, polyphosphazenes, PHA-PEG, poly(tyrosine carbonates), poly(tyrosine arylates), polyanhydrides, poly(hydroxyethyl methacylate), poly(N-acylhydroxyproline)esters, poly(N-palmitoyl hydroxyproline)esters, polyphosphazenes, and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

8. The medical article of claim 7, wherein the PHA is selected from a group consisting of poly(α

-hydroxyacids), poly(β

-hydroxyacids), poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-valerate), poly(3-hydroxyproprionate), poly(3-hydroxyhexanoate), poly(4-hydroxybutyrate), poly(4-hydroxyvalerate), or poly(4-hydroxyhexanoate), poly(hydroxyvalerate), and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

9. The medical article of claim 1, wherein the plasticizing agent comprises a component that is diagnostic, bioactive, biobenefical, or a combination thereof.

10. The medical article of claim 1, wherein the plasticizing agent comprises a component that is water-soluble, lipid soluble, or a combination thereof.

11. The medical article of claim 1, wherein the plasticizing agent comprises a component that is biodegradable.

12. The medical article of claim 1, wherein the plasticizing agent comprises a component selected from a group consisting of low molecular weight polymers, copolymers and oligomers;

small organic molecules;

lactic acid oligomers;

dimers of cyclic lactic acid and glycolic acid;

hydrogen bond forming organic compounds;

polyols;

alkanols;

sugar alcohols and anhydrides of sugar alcohols;

polyethers;

esters;

polyesters;

aliphatic acids;

saturated and unsaturated fatty acids;

fatty acid esters;

fatty alcohols;

cholesterol;

steroids;

phospholipids;

proteins;

oils;

silicones;

acetylated monoglycerides;

diglycerides;

triglycerides;

amides;

acetamides;

sulfoxides;

sulfones;

pyrrolidones;

oxa acids;

diglycdlic acids; and

any derivatives, analogs, homologues, congeners, copolymers and combinations thereof.

13. The medical article of claim 1, wherein the plasticizing agent comprises a component selected from a group consisting of lactic acid;

dimers of cyclic lactic acid and glycolic acid;

poly(ethylene glycol), poly(propylene glycol), poly(vinyl pyrrolidone), phosphorylcholine, glycosaminoglycans, phospholipids, carboxymethylcellulose, hyaluronic acid, heparin, hirudin, poly(acrylamide methyl propane sulfonic acid), poly(styrene sulfonate), sulfonated dextran, dermatan sulfate, RGD, collagen, chitin, chitosan, elastin and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

14. The medical article of claim 13, wherein the poly(ethylene glycol) has a molecular weight of less than 1500 Daltons.

15. The medical article of claim 1, wherein the plasticizing agent comprises a component selected from a group consisting of castor oil, fish oil, garlic oil, ethanol, xylene, dimethyl formamide, dimethyl sulfoxide, propylene glycol, glycerol, lecithin, and derivatives and combinations thereof.

16. The medical article of claim 1, wherein the plasticizing agent is localized in high-strain areas of the implant.

17. The medical article of claim 1, wherein the plasticizing agent leaches sufficiently from the implant in a subject in less than an amount of time required for a change in a required dimension of the implant in an amount ranging from about 0.1% to about 50%.

18. The medical article of claim 17, wherein the implant comprises a stent or a vena cava filter, the required dimension is a diameter of the stent or vena cava filter following deployment of the stent or vena cava filter in a subject, and the change is a reduction in the diameter of the stent or vena cava filter ranging from about 0.1% to about 20%.

19. The medical article of claim 1, wherein the implant comprises pores that were created through the use of a pore forming agent.

20. The medical article of claim 1, wherein the implant comprises an osmotic pump to enhance the leaching of the plasticizer from the implant.

21. A method of producing a medical article comprising a temporary plasticizing agent, wherein the method comprises

combining a polymer with a plasticizing agent capable of sufficiently increasing a strain-to-failure in the polymeric material to prevent or reduce a formation of cracks in the polymeric material while placing an implant in a subject, wherein the plasticizing agent leaches from the polymeric material after placing the implant in the subject to provide a sufficient rigidity in the polymeric material, and wherein the plasticizing agent leaches from the polymeric material in less than an amount of time necessary for a required dimension of the implant to change substantially in response to a stress.

22. The method of claim 21, wherein the implant comprises a stent or a vena cava filter.

23. The method of claim 22, wherein the stent is selected from a group consisting of vascular stents, renal stents, biliary stents, pulmonary stents and gastrointestinal stents.

24. The method of claim 21, wherein the implant comprises a biodegradable polymer.

25. The method of claim 21, wherein the implant comprises a polymer selected from a group consisting of polyesters, polyhydroxyalkanoates (PHAs), poly(ester amides);

amino acids;

poly(ethylene glycol) (PEG) and/or alcohol groups, polycaprolactones, poly(L-lactide), poly(D,L-lactide), poly(D,L-lactide-co-PEG) block copolymers, poly(D,L-lactide-co-trimethylene carbonate), polyglycolides, poly(lactide-co-glycolide), polydioxanones, polyorthoesters, polyanhydrides, poly(glycolic acid-co-trimethylene carbonate), polyphosphoesters, polyphosphoester urethanes, poly(amino acids), polycyanoacrylates, poly(trimethylene carbonate), poly(imino carbonates), polycarbonates, polyurethanes, copoly(ether-esters), polyalkylene oxalates, polyphosphazenes, PHA-PEG, poly(tyrosine carbonates), poly(tyrosine arylates), polyanhydrides, poly(hydroxyethyl methacylate), poly(N-acylhydroxyproline)esters, poly(N-palmitoyl hydroxyproline)esters, polyphosphazenes, and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

26. The method of claim 25, wherein the PHA is selected from a group consisting of poly(α

-hydroxyacids), poly(β

-hydroxyacids), poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-valerate), poly(3-hydroxyproprionate), poly(3-hydroxyhexanoate), poly(4-hydroxybutyrate), poly(4-hydroxyvalerate), or poly(4-hydroxyhexanoate), poly(hydroxyvalerate), and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

27. The method of claim 21, wherein the plasticizing agent is diagnostic, bioactive, biobenefical, or a combination thereof.

28. The method of claim 21, wherein the plasticizing agent comprises a component that is water-soluble.

29. The method of claim 21, wherein the plasticizing agent comprises a component that is lipid-soluble.

30. The method of claim 21, wherein the plasticizing agent comprises a component that is biodegradable.

31. The method of claim 21, wherein the plasticizing agent comprises a component selected from a group consisting of low molecular weight polymers, copolymers and oligomers;

small organic molecules;

lactic acid oligomers;

dimers of cyclic lactic acid and glycolic acid;

hydrogen bond forming organic compounds;

polyols;

alkanols;

sugar alcohols and anhydrides of sugar alcohols;

polyethers;

esters;

polyesters;

aliphatic acids;

saturated and unsaturated fatty acids;

fatty acid esters;

fatty alcohols;

cholesterol;

steroids;

phospholipids;

proteins;

oils;

silicones;

acetylated monoglycerides;

diglycerides;

triglycerides;

amides;

acetamides;

sulfoxides;

sulfones;

pyrrolidones;

oxa acids;

diglycolic acids; and

any derivatives, analogs, homologues, congeners, copolymers and combinations thereof.

32. The method of claim 21, wherein the plasticizing agent comprises a component selected from a group consisting of lactic acid;

dimers of cyclic lactic acid and glycolic acid;

poly(ethylene glycol), poly(propylene glycol), poly(vinyl pyrrolidone), phosphorylcholine, glycosaminoglycans, phospholipids, carboxymethylcellulose, hyaluronic acid, heparin, hirudin, poly(acrylamide methyl propane sulfonic acid), poly(styrene sulfonate), sulfonated dextran, dermatan sulfate, RGD, collagen, chitin, chitosan, elastin and any derivatives, analogs, homologues, congeners, salts, copolymers and combinations thereof.

33. The method of claim 32, wherein the poly(ethylene glycol) has a molecular weight of less than 1500 Daltons.

34. The method of claim 21, wherein the plasticizing agent comprises a component selected from a group consisting of castor oil, fish oil, garlic oil, ethanol, xylene, dimethyl formamide, dimethyl sulfoxide, propylene glycol, glycerol, lecithin, and derivatives and combinations thereof.

35. The method of claim 21, wherein the plasticizing agent is localized in high-strain areas of the implant.

36. The method of claim 21, wherein the plasticizing agent leaches sufficiently from the implant in a subject in less than an amount of time required for a change in a required dimension of the implant in an amount ranging from about 0.1% to about 50%.

37. The method of claim 21, wherein the implant comprises a stent or a vena cava filter, the required dimension is a diameter of the stent or vena cava filter following deployment of the stent or vena cava filter in a subject, and the change is a reduction in the diameter of the stent or vena cava filter ranging from about 0.1% to about 20%.

38. The method of claim 21, wherein the implant comprises pores that were created through the use of a pore forming agent.

39. The method of claim 21, wherein the implant comprises an osmotic pump to enhance leaching of the plasticizer from the implant.