Coated vaso-occlusive device and methods for treatment of aneurysms

• US 10,034,966 B2
• Filed: 05/19/2017
• Issued: 07/31/2018
• Est. Priority Date: 03/12/2013
• Status: Active Grant

• Current Assignee: Carnegie Mellon University
• Original Assignee: Carnegie Mellon University
• Inventors: Bettinger, Christopher J., Horowitz, Michael Bruce
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Truong, Quanglong N
• Application Number:
  US15/599,634
• Publication Number:
  US 20180008748A1
• Time in Patent Office: 438 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 creating and stabilizing a blood clot in a patient, comprising:

inducing clot formation in a patient'"'"'s vasculature; and

contacting the clot with genipin or a crosslinking genipin derivative to stabilize the clot.

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

3. The method of claim 1, wherein the step of inducing clot formation in the patient comprises feeding a vaso-occlusive device into the patient'"'"'s vasculature to induce clot formation.

4. The method of claim 3, wherein the vaso-occlusive device is an embolism coil.

5. The method of claim 3, wherein the genipin or cross-linking genipin derivative comprises a filament comprising core and a controlled release coating layer on the core comprising the genipin or a crosslinking genipin derivative.

6. The method of claim 5, wherein the filament comprises between the core substrate and the controlled release coating layer a polymeric intermediary layer.

7. The method of claim 6, wherein the polymeric intermediary layer is a hydrogel, or wherein the controlled release coating layer is a non-bioerodible polymer comprising the genipin or crosslinking genipin derivative.

8. The method of claim 3, wherein the genipin or crosslinking genipin derivative is provided as a filament comprising a controlled-release genipin or crosslinking genipin derivative.

9. The method of claim 1, wherein the clot is contacted with a crosslinking derivative of genipin.

10. The method of claim 9, wherein the cross-linking derivative of genipin is a compound according to formula 2, or a stereoisomer or pharmaceutically acceptable salt thereof:

11. The method of claim 10, wherein R1 is —

OR4, where R4 is —

H or C_1-3 alkyl.

12. The method of claim 11, wherein R2 is H or C_1-3 alkyl and/or R3 is —

CH₂—

OH, —

CH₂—

CH₂—

OH, or —

CH₂—

CH₂—

CH₂—

OH.

13. The method of claim 10, wherein R2 is H or C_1-3 alkyl.

14. The method of claim 10, wherein R3 is —

CH₂—

OH, —

CH₂—

CH₂—

OH, or —

CH₂—

CH₂—

CH₂—

OH.

15. A vaso-occluding catheter device comprising a sheath and first and second filaments within the sheath, wherein the second filament comprises, as a core substrate or a coating thereon, genipin or a crosslinking genipin derivative.

16. The device of claim 15, wherein the crosslinking derivative of genipin is a compound according to formula 2, or a stereoisomer or a pharmaceutically acceptable salt thereof:

17. The device of claim 16, wherein R1 is —

OR4, where R4 is —

H or C_1-3 alkyl.

18. The device of claim 17, wherein R2 is H or C_1-3 alkyl and/or R3 is —

CH₂—

OH, —

CH₂—

CH₂—

OH, or —

CH₂—

CH₂—

CH₂—

OH.

19. The device of claim 16, wherein R2 is H or C_1-3 alkyl.

20. The device of claim 16, wherein R3 is —

CH₂—

OH, —

CH₂—

CH₂—

OH, or —

CH₂—

CH₂—

CH₂—

OH.