Embolization plugs for blood vessels

• US 5,456,693 A
• Filed: 08/25/1994
• Issued: 10/10/1995
• Est. Priority Date: 09/21/1992
• Status: Expired due to Term

• Current Assignee: Vitaphore Corporation
• Original Assignee: Vitaphore Corporation
• Inventors: Raeder-Devens, Jennifer, Conston, Stanley R., Dapper, Gregory S., Yamamoto, Ronald, Murphy, Aileen L.
• Primary Examiner(s): Pellegrino, Stephen C.
• Assistant Examiner(s): LEWIS, WILLIAM W
• Application Number:
  US08/297,271
• Time in Patent Office: 411 Days
• Field of Search: 604/11, 604/55, 604/368, 604/369, 128/831, 128/843, 128/899, 128/DIG. 8, 606/191-194, 606/154, 514/801, 514/773
• US Class Current: 606/192
• 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 17/12045 double occlusion, e.g. during anastomosis
• CPC Class Codes: A61B 17/1219 expandable in contact with liquids
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable or resorptive
• CPC Class Codes: A61L 17/005 containing a biologically active substance, e.g. a medicament or a biocide
• CPC Class Codes: A61L 17/08 of animal origin, e.g. catgut, collagen
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 2300/434 of enzymes
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices
• CPC Class Codes: Y10S 128/08 Collagen

Abstract

A bioresorbable and hemostatic plug for embolization made from a collagen piece is compressed so as to be longitudinally insertable into a tubular biological vessel such as a blood vessel to be occluded. The collagen piece is capable of expanding radially inside the vessel by absorbing fluid such as the blood and thereby providing mechanical fixation in and occlusion of the vessel. Two such collagen pieces may be used with a spacer of a different material in between. Different kinds of therapeutic agents can be bonded to or physically absorbed by the collagen pieces so as to be delivered to the site of occlusion.

Claims

1. A plug which, in a compressed condition, is longitudinally insertable into a tubular biological vessel, said plug comprising a piece having unconstrained dimension greater than the inner diameter of said vessel, said piece having a modulus at 60% compression greater than 0.15 g/mm² and being capable of expanding radially inside said vessel by absorbing fluid and thereby providing mechanical fixation in and occlusion of said vessel.

2. The plug of claim 1 wherein said piece comprises collagen.

3. The plug of claim 1 wherein said piece is porous, having pores with diameters greater than 50 microns, said piece being capable of promoting cellular ingrowth.

4. The plug of claim 1 wherein said piece comprises cross-linked collagen with shrink temperature higher than 55°

C.

5. The plug of claim 1 wherein said piece comprises crosslinked collagen with modulus at 60% volumetric compression greater than 1.3 g/mm².

6. The plug of claim 1 wherein said piece contains one or more active agents selected from the group consisting of sclerosing agents, clotting agents, hyperosmotic agents, surface active agents, antibiotics, tissue attachment factors, protease inhibitors, and anti-neoplastic agents.

7. The plug of claim 6 wherein said one or more active agents are covalently, ionically or hydrophobically bound to said piece.

8. The plug of claim 6 wherein said one or more active agents are physically absorbed by said piece.

9. The plug of claim 6 wherein said hyperosmotic agents include polyethylene glycol with molecular weight less than 2000, said sclerosing agents include morrhuate sodium, ethanolamine oleate, and tetradecyl sulfate, said clotting agents include Factors I-VIII, thrombin and fibrinogen, said antibiotics include tobramycin, gentamycin and vancomycin, said tissue attachment factors include vitronectin, fibronectin and laminin, said protease inhibitors include aprotinin and ethylenediaminetetraacetate, and said anti-neoplastic agents include 5-fluorouracil, methotrexate, nitroso-ureas, cisplatin, cyclophosphamide, dacarbazine, dactinomycin, doxorubicin, etoposide, mitomycin, vinblastine, and vindesine.

10. The plug of claim 1 wherein said piece can be compressed from its unconstrained state such that its external radial dimensions can be reduced by a factor of at least 2.5.

11. The plug of claim 1 comprising two pieces made from collagen and a spacer disposed between said two pieces, said pieces being each capable of expanding radially inside said vessel by absorbing fluid and thereby providing mechanical fixation in and occlusion of said vessel.

12. The plug of claim 11 wherein said pieces have unconstrained dimension greater than the inner diameter of said vessel and are in compressed condition before said plug is inserted into said vessel.

13. The plug of claim 11 wherein said pieces are porous, having pores with diameters greater than 50 microns, said pieces being capable of promoting cellular ingrowth.

14. The plug of claim 11 wherein said plug comprises bioerodible material with a controllable rate of bioresorption.

15. The plug of claim 11 wherein said pieces comprise crosslinked collagen with shrink temperature higher than 55°

C.

16. The plug of claim 11 wherein said pieces comprise crosslinked collagen with modulus at 60% volumetric compression greater than 1.3 g/mm².

17. The plug of claim 11 wherein said spacer contains one or more active agents selected from the group consisting of sclerosing agents, clotting agents, hyperosmotic agents, surface active agents, antibiotics, tissue attachment factors, protease inhibitors, anti-neoplastic agents and a radiopaque material.

18. The plug of claim 17 wherein said one or more active agents are covalently, ionically or hydrophobically bound to said piece.

19. The plug of claim 17 wherein said one or more active agents are physically absorbed by said piece.

20. The plug of claim 17 wherein said hyperosmotic agents include polyethylene glycol with molecular weight less than 2000, said sclerosing agents include morrhuate sodium, ethanolamine oleate, and tetradecyl sulfate, said clotting agents include Factors I-VIII, thrombin and fibrinogen, said antibiotics include tobramycin, gentamycin and vancomycin, said tissue attachment factors include vitronectin, fibronectin and laminin, said protease inhibitors include aprotinin and ethylenediaminetetraacetate, and said anti-neoplastic agents include 5-fluorouracil, methotrexate, nitroso-ureas, cisplatin, cyclophosphamide, dacarbazine, dactinomycin, doxorubicin, etoposide, mitomycin, vinblastine, and vindesine.

21. A plug which is compressible and is longitudinally insertable into a tubular biological vessel when in a compressed condition, said plug comprising a piece having unconstrained dimension greater than the inner diameter of said vessel, said piece comprising bioerodible material with a controllable rate of bioresorption, having a modulus at 60% compression greater than 0.15 g/mm² and being capable of expanding radially inside said vessel by absorbing fluid and thereby providing mechanical fixation in and occlusion of said vessel.