Bioabsorbable polymeric implants and a method of using the same to create occlusions

• US 20020040239A1
• Filed: 02/16/2001
• Published: 04/04/2002
• Est. Priority Date: 01/27/1998
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Murayama, Yuichi, Vinuela, Fernando
• Granted Patent: US 7,070,607 B2
• Time in Patent Office: Days
• US Class Current: 623/1.34
• CPC Class Codes: A61B 17/12022 Occluding by internal devices, e.g. balloons or releasable wires plugging an opening in the wall of an organ A61B17/0057; occluders for the cervical canal A61F6/146; vas deferens occluders A61F6/20
• CPC Class Codes: A61B 17/12113 within an aneurysm
• CPC Class Codes: A61B 17/12145 having a pre-set deployed three-dimensional shape methods of manufacturing A61B2017/00526
• CPC Class Codes: A61B 17/1215 comprising additional materials, e.g. thrombogenic, having filaments, having fibers, being coated
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable, resorptive for implantable prostheses A61F2210/0004
• CPC Class Codes: A61B 2017/1205 Introduction devices
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices artificial blood vessels A61L27/507
• CPC Class Codes: A61L 31/043 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/082 Inorganic materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 31/18 Materials at least partially X-ray or laser opaque
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A new embolic agent, bioabsorbable polymeric material (BPM) is incorporated to a Guglielmi detachable coil (GDC) to improve long-term anatomic results in the endovascular treatment of intracranial aneurysms. The embolic agent, comprised at least in part of at least one biocompatible and bioabsorbable polymer and growth factors, is carried by hybrid bioactive coils and is used to accelerate histopathologic transformation of unorganized clot into fibrous connective tissue in experimental aneurysms. An endovascular cellular manipulation and inflammatory response are elicited from implantation in a vascular compartment or any intraluminal location. Thrombogenicity of the biocompatible and bioabsorbable polymer is controlled by the composition of the polymer. The coil further is comprised at least in part of a growth factor or more particularly a vascular endothelial growth factor, a basic fibroblast growth factor or other growth factors. The biocompatible and bioabsorbable polymer is in the illustrated embodiment at least one polymer selected from the group consisting of polyglycolic acid, poly˜glycolic acid/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L-lactide. Polydioxanone, polycarbonates, and polyanhydrides.

Claims

1. An endovascular apparatus for developing an inflammatory response in a body cavity with cellular manipulation comprising:

a separable implant comprised at least in part of at least one biocompatible and bioabsorbable polymer; and

an endovascular placement device associated with said separable implant adapted to dispose said implant into said body cavity.

2. The apparatus of claim 1 wherein said implant further is comprised at least in part of a noncollagenous protein.

3. The apparatus of claim 1 wherein said implant further is comprised at least in part of a growth factor.

4. The apparatus of claim 3 wherein said implant further is comprised at least in part of a one selected from the group of VEGF, b-FGF, TGF, PDGF or mixtures thereof.

5. The apparatus of claim 3 wherein said implant further is comprised at least in part of a basic fibroblast growth factor.

6. The apparatus of claim 4 wherein said implant further is comprised at least in part of a mixture of said vascular endothelial growth factor and a basic fibroblast growth factor.

7. The apparatus of claim 1 wherein said biocompatible and bioabsorbable polymer is at least one polymer selected from the group consisting of polyglycolic acid, poly˜

glycolic acid/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L-lactide, polydioxanone, polycarbonates, and polyanhydrides.

8. The apparatus of claim 2 wherein said biocompatible and bioabsorbable protein is at least one protein selected from the group consisting of fibrinogen, fibronectin, vitronectin, laminin, and gelatin.

9. The apparatus of claim 1 wherein a radio-opaque material is disposed on said implant.

10. The apparatus of claim 1 wherein said implant composed of a radio-opaque material, and wherein said biocompatible and bioabsorbable polymer or protein is disposed thereon.

11. The apparatus of claim 1 wherein said biocompatible and bioabsorbable polymer promotes cellular manipulation, controlled inflammatory response and vascular healing.

13. The method of claim 12 further providing said implant with a noncollagenous protein.

14. The method of claim 12 further providing said implant with a growth factor.

15. The method of claim 14 wherein providing said implant with a growth factor comprises providing said implant with a vascular endothelial growth factor.

16. The method of claim 14 wherein providing said implant with a growth factor comprises providing said implant with a basic fibroblast growth factor.

17. The method of claim 15 wherein providing said implant with a growth factor comprises providing said implant with a mixture of said vascular endothelial growth factor and a basic fibroblast growth factor.

18. The method of claim 12 wherein providing said separable implant comprised with said biocompatible and bioabsorbable polymer comprises providing said implant with at least one polymer selected from the group consisting of polyglycolic acid, poly˜

glycolic acid/poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L-lactide, polydioxanone, polycarbonates, and polyanhydrides.

19. The method of claim 13 wherein providing said separable implant comprised with said biocompatible and bioabsorbable protein comprising providing at least one protein selected from the group consisting of fibrinogen, fibronectin, vitronectin, laminin, and gelatin.

20. The method of claim 12 wherein providing said implant provides a implant composed of said biocompatible and bioabsorbable polymer with a radio-opaque material is disposed thereon.

21. The method of claim 12 wherein providing said implant provides a implant composed of a radio-opaque material with said biocompatible and bioabsorbable polymer is disposed thereon.

22. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer does not elicit intense chronic foreign body reaction.

23. The apparatus of claim 1 where said endovascular placement device is used to dispose said implant at an implantation site and where said biocompatible and bioabsorbable polymer is gradually absorbed and does not leave residua in said implantation site.

24. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer is faster degrading and provides a stronger inflammatory reaction than metal coils.

25. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer has a selected composition to provide a controlled degradation time to thereby control intravascular inflammatory reactions.

26. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer regenerates tissue through the interaction of immunologic cells.

27. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer stimulates cellular infiltration and proliferation in the process of degradation to accelerate fibrosis.

28. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer accelerates fibrosis within an aneurysm to more strongly anchor said implant than does metal coils.

29. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer is characterized by generating more connective tissue and a less unorganized clot than metal coils so that an aneurysm in which said implant is disposed is more resistant to a water hammer effect of pulsatile blood than when treated by metal coils.

30. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer restricts coil compaction by accelerated scar formation.

31. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer restricts aneurysm recanalization by accelerated scar formation.

32. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer induces organized connective tissue to fill an aneurysm and to retract said aneurysm over time due to maturation of collagen fibers to reduce aneurysm size and decrease aneurysm compression on brain parenchyma or cranial nerves.

33. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer is less thrombogenic than metal coils and accelerates aneurysm healing with less thrombogenicity.

34. The apparatus of claim 1 where said biocompatible and bioabsorbable polymer comprises a mixture of polyglycolic/poly-L-lactic acid copolymers with a 90/10 molar ratio of glycolic to L-lactic acid.

35. The apparatus of claim 1 where said implant is a hybrid bioactive coil.

36. The apparatus of claim 35 where said hybrid bioactive coil is a composite of said biocompatible and bioabsorbable polymer and an inert biocompatible coil.

37. The apparatus of claim 36 where said inert biocompatible coil is a platinum coil.

38. The apparatus of claim 36 where said composite of said biocompatible and bioabsorbable polymer and an inert biocompatible coil comprises a layer of said biocompatible and bioabsorbable polymer on said inert biocompatible coil.

39. The apparatus of claim 36 where said composite of said biocompatible and bioabsorbable polymer and an inert biocompatible coil comprises threads of said biocompatible and bioabsorbable polymer attached to said inert biocompatible coil.

12. A method for creating an inflammatory response in a body cavity comprising:

providing a separable implant comprised at least in part of at least one biocompatible and bioabsorbable polymer; and

disposing said separable implant into said body cavity.