Mechanical apparatus and method for dilating and delivering a therapeutic agent to a site of treatment

• US 20040267356A1
• Filed: 06/10/2004
• Published: 12/30/2004
• Est. Priority Date: 04/30/2002
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Inventors: Segal, Jerome, Scott, Neal
• Granted Patent: US 7,519,418 B2
• Time in Patent Office: Days
• US Class Current: 623/1.42
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 29/02 Dilators made of swellable material balloon catheters for angioplasty A61M25/104

Abstract

A mechanical dilatation and medicament delivery device for enlarging a flow passage of a vessel by dilating and delivering a liposome or micelle-encapsulated therapeutic agent or medicament to an obstruction in the vessel. The present invention comprises a substantially cylindrically shaped expansion member and includes a means engaged to the expansion member for altering the distance between the proximal end and the distal end of the expansion member thereby transforming the expansion member between a diametrically contracted configuration to diametrically expanded configuration. A liposome or micelle-encapsulated therapeutic agent or medicament is coated on either the expansion member, or incorporated into a substrate coated on the expansion member.

The present method comprises the steps of advancing the coated expansion member to the obstruction in a vessel and applying opposed forces on said expansion member in an axial direction to move the expansion member to an expanded configuration wherein the expansion member dilates the obstruction and the expansion member either passively or actively delivers a liposome or micelle-encapsulated therapeutic agent or medicament to the obstruction.

Claims

1. An apparatus for dilating and delivering a medicament to an obstruction within a vascular segment or a body passageway which comprises:

a catheter having a distal end and a proximal end;

a substantially cylindrical shaped expansion member located on said distal end of said catheter, said expansion member having a first end and a second end, said first end being a distance from said second end;

an altering means engagable to said first end and said second end of said expansion member for altering said first distance therebetween to move said expansion member between a first configuration wherein said expansion member is characterized by a first diameter and a second configuration wherein said expansion member is characterized by a second diameter, said second diameter being greater than said first diameter; and

a therapeutic agent or medicament incorporated within a liposome coated on at least a portion of said expansion member.

10. An apparatus as recited in claim 1 or 2 further comprising a plurality of said liposome encapsulated medicaments coated on at least a portion of said expansion member.

24. An apparatus as recited in claim 1 or 16 further comprising a plurality of said micelle encapsulated medicaments coated on at least a portion of said expansion member.

26. An apparatus as recited in claim 1, 16 or 25, wherein said micelle encapsulated medicaments are agents that function to stimulate cell growth or cell division.

27. An apparatus as recited in claim 1, 16, or 25, where said liposome medicaments is a fibroblast growth factor, endothelial cell growth factor, growth hormone or erythopoeitin.

2. An apparatus for dilating and introducing molecules into cells within a vascular segment or a body passageway which comprises:

a catheter having a distal end and a proximal end;

a substantially cylindrical shaped expansion member located on said distal end of said catheter, said expansion member having a first end and a second end, said first end being a distance from said second end;

an altering means engagable to said first end and said second end of said expansion member for altering said first distance therebetween to move said expansion member between a first configuration wherein said expansion member is characterized by a first diameter and a second configuration wherein said expansion member is characterized by a second diameter, said second diameter being greater than said first diameter; and

a lipsosome encapsulated medicament coated on at least a portion of said expansion member.

3. An apparatus as recited in claim 2 wherein said expansion member defines a flow passageway extending between said first end and said second end of the expansion member.

4. An apparatus as recited in claim 2, wherein said liposome encapsulated medicament is an anticoagulant selected from the group consisting of D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, an antithrombin compound, a platelet receptor antagonist, an anti-thrombin antibody, an anti-platelet receptor antibody, hirudin, hirulog, phe-pro-arg-chloromethyketone (Ppack), Factor VIIa, Factor Xa, aspirin, clopridogrel, ticlopidine, a prostaglandin inhibitor, a platelet inhibitor and a tick anti-platelet peptide, and combinations thereof.

5. An apparatus as recited in claim 2, wherein said liposome encapsulated medicament is a promoter of vascular cell growth selected from the group consisting of a growth factor stimulator, a growth factor receptor agonist, a transcriptional activator, and a translational promoter, and combinations thereof.

6. An apparatus as recited in claim 2 wherein said liposome encapsulated medicament is an inhibitor of vascular cell growth selected from the group consisting of a growth factor inhibitor, a growth factor receptor antagonist, a transcriptional repressor, a translational repressor, an antisense DNA, an antisense RNA, synthetic DNA compounds, especially those with backbones that have been modified to inhibit enzymatic degradation (e.g. phosphorothioate compounds and morpholino diamidate compounds), a replication inhibitor, an inhibitory antibody, an antibody directed against growth factors, a bifunctional molecule consisting of a growth factor and a cytotoxin, and a bifunctional molecule consisting of an antibody and a cytotoxin, double stranded DNA, single stranded DNA, single stranded RNA and a double stranded RNA and combinations thereof.

7. An apparatus as recited in claim 2, wherein said liposome encapsulated medicament is selected from the group consisting of a cholesterol-lowering agent, a vasodilating agent, and agents which interfere with endogenous vasoactive mechanisms, estrogen, testosterone, steroid hormones, cortisol, dexamethasone, corticosteroids, thyroid hormones, thyroid hormones analogs, throid hormones antagonist, adrenocorticotrophic hormone, thyroid stimulating hormone, thyroid releasing factor, thyroid releasing factor analogs, thyroid releasing factor antagonists and combinations thereof.

8. An apparatus as recited in claim 2, wherein said liposome encapsulated medicament is a smooth muscle inhibitor selected from the group consisting of an agent that modulates intracellular calcium binding proteins, a receptor blocker for contractile agonists, an inhibitor of the sodium/hydrogen antiporter, a protease inhibitor, a nitrovasodilator, a phosphodiesterase inhibitor, a phenothiazine, a growth factor receptor agonist, an anti-mitotic agent, an immunosuppressive agent, and a protein kinase inhibitor, and combinations thereof.

9. An apparatus as recited in claim 2, wherein said liposome encapsulated medicament is a compound that inhibits cellular proliferation, Paclitaxel, Rapamycin, Actinomycin D, Methotrexate, Doxorubicin, cyclophosphamide, and 5-fluorouracil, 6-mercapatopurine, 6-thioguanine, cytoxan, cytarabinoside, cis-platin, chlorambucil, busulfan, and any other drug that can inhibit cell proliferation, and combinations thereof.

13. An apparatus as recited in claim 2, wherein said liposome encapsulated medicaments are agents that function to stimulate cell growth or cell division.

14. An apparatus as recited in claim 2, where said liposome medicaments is a fibroblast growth factor, endothelial cell growth factor, growth hormone or erythopoeitin.

11. A mechanical dilatation and medicament delivery device comprising:

a catheter having a distal end and a proximal end, said catheter having one or more lumens;

an substantially cylindrically shaped expandable mesh positioned on said distal end adapted to dilate an obstruction in a vessel, said mesh having a first contracted diameter and a second expanded diameter, said second expanded diameter being larger than said first contracted diameter; and

said mechanical dilatation and medicament delivery device being adapted to dilate said obstruction and expose said obstruction to a liposome medicament while allowing blood or bodily fluids to flow through said substantially cylindrically shaped expandable mesh.

15. An apparatus for dilating and delivering a medicament to an obstruction within a vascular segment or a body passageway which comprises:

a catheter having a distal end and a proximal end;

a substantially cylindrical shaped expansion member located on said distal end of said catheter, said expansion member having a first end and a second end, said first end being a distance from said second end;

an altering means engagable to said first end and said second end of said expansion member for altering said first distance therebetween to move said expansion member between a first configuration wherein said expansion member is characterized by a first diameter and a second configuration wherein said expansion member is characterized by a second diameter, said second diameter being greater than said first diameter; and

a therapeutic agent or medicament incorporated within a micelle and coated on at least a portion of said expansion member.

16. An apparatus for dilating and introducing molecules into cells within a vascular segment or a body passageway which comprises:

a catheter having a distal end and a proximal end;

a substantially cylindrical shaped expansion member located on said distal end of said catheter, said expansion member having a first end and a second end, said first end being a distance from said second end;

an altering means engagable to said first end and said second end of said expansion member for altering said first distance therebetween to move said expansion member between a first configuration wherein said expansion member is characterized by a first diameter and a second configuration wherein said expansion member is characterized by a second diameter, said second diameter being greater than said first diameter; and

a or micelle encapsulated medicament coated on at least a portion of said expansion member.

17. An apparatus as recited in claim 16 wherein said expansion member defines a flow passageway extending between said first end and said second end of the expansion member.

18. An apparatus as recited in claim 16, wherein said liposome or micelle-encapsulated medicament is an anticoagulant selected from the group consisting of D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, an antithrombin compound, a platelet receptor antagonist, an anti-thrombin antibody, an anti-platelet receptor antibody, hirudin, hirulog, phe-pro-arg-chloromethyketone (Ppack), Factor VIIa, Factor Xa, aspirin, clopridogrel, ticlopidine, a prostaglandin inhibitor, a platelet inhibitor and a tick anti-platelet peptide, and combinations thereof.

19. An apparatus as recited in claim 16, wherein said micelle encapsulated medicament is a promoter of vascular cell growth selected from the group consisting of a growth factor stimulator, a growth factor receptor agonist, a transcriptional activator, and a translational promoter, and combinations thereof.

20. An apparatus as recited in claim 16 wherein said micelle encapsulated medicament is an inhibitor of vascular cell growth selected from the group consisting of a growth factor inhibitor, a growth factor receptor antagonist, a transcriptional repressor, a translational repressor, an antisense DNA, an antisense RNA, synthetic DNA compounds, especially those with backbones that have been modified to inhibit enzymatic degradation (e.g. phosphorothioate compounds and morpholino diamidate compounds), a replication inhibitor, an inhibitory antibody, an antibody directed against growth factors, a bifunctional molecule consisting of a growth factor and a cytotoxin, and a bifunctional molecule consisting of an antibody and a cytotoxin, double stranded DNA, single stranded DNA, single stranded RNA and a double stranded RNA and combinations thereof.

21. An apparatus as recited in claim 16, wherein said micelle encapsulated medicament is selected from the group consisting of a cholesterol-lowering agent, a vasodilating agent, and agents which interfere with endogenous vasoactive mechanisms, estrogen, testosterone, steroid hormones, cortisol, dexamethasone, corticosteroids, thyroid hormones, thyroid hormones analogs, throid hormones antagonist, adrenocorticotrophic hormone, thyroid stimulating hormone, thyroid releasing factor, thyroid releasing factor analogs, thyroid releasing factor antagonists and combinations thereof.

22. An apparatus as recited in claim 16, wherein said micelle encapsulated medicament is a smooth muscle inhibitor selected from the group consisting of an agent that modulates intracellular calcium binding proteins, a receptor blocker for contractile agonists, an inhibitor of the sodium/hydrogen antiporter, a protease inhibitor, a nitrovasodilator, a phosphodiesterase inhibitor, a phenothiazine, a growth factor receptor agonist, an anti-mitotic agent, an immunosuppressive agent, and a protein kinase inhibitor, and combinations thereof.

23. An apparatus as recited in claim 16, wherein said micelle encapsulated medicament is a compound that inhibits cellular proliferation, Paclitaxel, Rapamycin, Actinomycin D, Methotrexate, Doxorubicin, cyclophosphamide, and 5-fluorouracil, 6-mercapatopurine, 6-thioguanine, cytoxan, cytarabinoside, cis-platin, chlorambucil, busulfan, and any other drug that can inhibit cell proliferation, and combinations thereof.

25. A mechanical dilatation and medicament delivery device 2omprising:

a catheter having a distal end and a proximal end, said catheter having one or more lumens;

an substantially cylindrically shaped expandable mesh positioned on said distal end adapted to dilate an obstruction in a vessel, said mesh having a first contracted diameter and a second expanded diameter, said second expanded diameter being larger than said first contracted diameter; and

said mechanical dilatation and medicament delivery device being adapted to dilate said obstruction and expose said obstruction to a micelle medicament while allowing blood or bodily fluids to flow through said expandable mesh.