Coated vaso-occlusive device for treatment of aneurysms

• US 9,655,999 B2
• Filed: 03/12/2014
• Issued: 05/23/2017
• Est. Priority Date: 03/12/2013
• Status: Active Grant

• Current Assignee: Carnegie Mellon University, University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: Carnegie Mellon University
• Inventors: Bettinger, Christopher J., Horowitz, Michael Bruce
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Truong, Quanglong
• Application Number:
  US14/775,078
• Publication Number:
  US 20160051733A1
• Time in Patent Office: 1,168 Days
• Field of Search: None
• CPC Class Codes: A61B 17/12031 complete occlusion
• 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: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2420/04 Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• 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 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 25/0045 multi-layered, e.g. coated coating materials A61L29/08
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A method is described herein for the treatment of intracranial aneurysms. The method comprises inserting into an aneurysm an embolism coil coated with a polymeric coating comprising a genipin, such as genipin or a derivative thereof, thereby increasing the stability of clots within the aneurysm. According to one example, the coating is a poly(L-lactide-co-glycolide) (PLGA) is used to release genipin to crosslink fibrin clots thereby creating more stable occlusions. Increased clotting can improve segregation of the weakened portion of the blood vessel from the rest of the vasculature and reduce the risk of recurrence.

Claims

1. A method of treating an aneurysm in a patient, comprising feeding a vaso-occlusive device and genipin or a crosslinking genipin derivative into a fundus of the aneurysm using a catheter.

2. The method of claim 1, in which the genipin or a crosslinking genipin derivative is incorporated into a bioerodible polymer.

3. The method of claim 1, in which the genipin or a crosslinking genipin derivative is incorporated into a non-bioerodible polymer.

4. The method of claim 1, in which either

the vaso-occlusive device comprises a core substrate and a controlled release coating layer on the core substrate comprising the genipin or a crosslinking genipin derivative, or

the genipin or crosslinking genipin derivative is fed into the fundus as a controlled-release second filament comprising the genipin or crosslinking genipin derivative.

5. The method of claim 4, in which the controlled release coating layer comprises genipin or a pharmaceutically acceptable salt thereof.

6. The method of claim 4, in which the controlled release coating layer comprises a crosslinking derivative of genipin or a pharmaceutically acceptable salt thereof.

7. The method of claim 4, in which the crosslinking derivative of genipin is a compound according to formula 2, or a stereoisomer or pharmaceutically acceptable salt thereof:

8. The method of claim 7, in which R1 is —

OR4, where R4 is —

H or C_1-3 alkyl.

9. The method of claim 8, in which R2 is H or C_1-3 alkyl and/or R3 is —

CH₂—

OH, —

CH₂—

CH₂—

OH, or —

CH₂—

CH₂—

CH₂—

OH.

10. The method of claim 7, in which R2 is H or C_1-3 alkyl.

11. The method of claim 7, in which R3 is —

CH₂—

OH, —

CH₂—

CH₂—

OH, or —

CH₂—

CH₂—

CH₂—

OH.

12. The method of claim 4, in which the device comprises between the core substrate and the controlled release coating layer a polymeric intermediary layer.

13. The method of claim 12, in which the polymeric intermediary layer is a hydrogel.

14. The method of claim 4, in which the controlled release coating layer is a bioerodible polymer comprising the genipin or crosslinking genipin derivative.

15. The method of claim 14, in which the bioerodible polymer is a polyester or a polyester-containing copolymer.

16. The method of claim 15, in which the polyester or polyester-containing copolymer is a poly(lactic-co-glycolic) acid (PLGA) copolymer.

17. The method of claim 14, in which the bioerodible polymer is selected from the group consisting of a polyanhydride, a polyanhydride-containing copolymer, a polyorthoester, and a polyorthoester-containing copolymer.

18. The method of claim 14, in which the bioerodible polymer is selected from the group consisting of poly(lactic acid) (PLA);

poly(trimethylene carbonate) (PTMC);

poly(caprolactone) (PCL);

poly(glycolic acid) (PGA);

poly(glycolide-co-trimethylenecarbonate) (PGTMC);

poly(L-lactide-co-glycolide) (PLGA);

polyethylene-glycol- (PEG-) containing block copolymers; and

polyphosphazenes.

19. The method of claim 4, in which the controlled release coating layer is a non-bioerodible polymer comprising the genipin or crosslinking genipin derivative.

20. A vaso-occluding catheter device comprising a sheath and at least a first filament comprising a core substrate within the sheath, wherein either:

the first filament comprises a controlled release coating layer on the core substrate comprising genipin or a crosslinking genipin derivative, or

the device comprises within the sheath a controlled-release second filament comprising a bioerodible polymer comprising genipin or a crosslinking genipin derivative.

21. The device of claim 20, in which the core substrate of the first filament is a metal.

22. The device of claim 21, in which the metal is platinum, a platinum alloy or nitinol.

23. The device of claim 20, in which the controlled release coating layer of the first filament comprises genipin or a pharmaceutically acceptable salt thereof.

24. The device of claim 20, in which the controlled release coating layer of the first filament comprises a crosslinking derivative of genipin or a pharmaceutically acceptable salt thereof.

25. The device of claim 24, in which the crosslinking derivative of genipin is a compound according to formula 2, or a stereoisomer or a pharmaceutically acceptable salt thereof:

26. The device of claim 25, in which R1 is —

OR4, where R4is —

H or C_1-3 alkyl.

27. The device of claim 26, in which R2 is H or C_1-3 alkyl and/or R3 is —

CH₂—

OH, —

CH₂—

CH₂—

OH, or —

CH₂—

CH₂—

CH₂—

OH.

28. The device of claim 25, in which R2 is H or C_1-3 alkyl.

29. The device of claim 25, in which R3 is —

CH₂—

OH, —

CH₂—

CH₂—

OH, or —

CH₂—

CH₂—

CH₂—

OH.

30. The device of claim 20, in which the first filament comprises between the core substrate and the controlled release coating layer a polymeric intermediary layer.

31. The device of claim 30, in which the polymeric intermediary layer is a hydrogel.

32. The device of claim 20, in which the controlled release coating layer of the first filament is a bioerodible polymer comprising the genipin or crosslinking genipin derivative.

33. The device of claim 32, in which the bioerodible polymer is a polyester or a polyester-containing copolymer.

34. The device of claim 33, in which the polyester or polyester-containing copolymer is a poly(lactic-co-glycolic) acid (PLGA) copolymer.

35. The device of claim 32, in which the bioerodible polymer is selected from the group consisting of a polyanhydride, a polyanhydride-containing copolymer, a polyorthoester, and a polyorthoester-containing copolymer.

36. The device of claim 32, in which the bioerodible polymer is selected from the group consisting of poly(lactic acid) (PLLA);

poly(trimethylene carbonate) (PTMC);

poly(caprolactone) (PCL);

poly(glycolic acid) (PGA);

poly(glycolide-co-trimethylenecarbonate) (PGTMC);

poly(L-lactide-co-glycolide) (PLGA);

polyethylene-glycol-(PEG-) containing block copolymers; and

polyphosphazenes.

37. The device of claim 20, in which the controlled release coating layer of the first filament is a non-bioerodible polymer comprising the genipin or crosslinking genipin derivative.