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

• US 20030100886A1
• Filed: 11/29/2001
• Published: 05/29/2003
• Est. Priority Date: 11/29/2001
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Segal, Jerome, Scott, Neal
• Granted Patent: US 7,488,313 B2
• Time in Patent Office: Days
• US Class Current: 604/509
• CPC Class Codes: A61M 2025/0004 having two or more concentrically arranged tubes for forming a concentric catheter system
• CPC Class Codes: A61M 2025/0008 having visible markings on its surface, i.e. visible to the naked eye, for any purpose, e.g. insertion depth markers, rotational markers or identification of type
• CPC Class Codes: A61M 2025/0175 having telescopic features, interengaging nestable members movable in relations to one another
• CPC Class Codes: A61M 2025/0183 Rapid exchange or monorail catheters
• 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
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

A mechanical dilatation and medicament delivery device for enlarging a flow passage of a vessel by dilating and delivering a 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 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 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 coated on at least a portion of said expansion member.

2. An apparatus as recited in claim 1 wherein said expansion member defines a flow passageway extending between said first end and said second end of the expansion member.

3. An apparatus as recited in claim 1 wherein said expansion member comprises a first plurality of flexible elongate elements helically wound in a first direction of rotation and a second plurality of flexible elongate elements helically wound in a second direction of rotation to form a braid.

4. An apparatus as recited in claim 1 wherein said expansion member is adapted to allow blood perfusion while said expansion member in either in said first diameter or in said second diameter.

5. An apparatus as recited in claim 1 wherein said therapeutic agent or medicament is incorporated into a non-therapeutic substrate.

6. An apparatus as recited in claim 1, wherein said therapeutic agent or 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.

7. An apparatus as recited in claim 1, wherein said therapeutic agent or 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.

8. An apparatus as recited in claim 1, wherein said therapeutic agent or 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, 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.

9. An apparatus as recited in claim 1, wherein said therapeutic agent or 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.

10. An apparatus as recited in claim 1, wherein said therapeutic agent or 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.

11. An apparatus as recited in claim 1, wherein said therapeutic agent or medicament is a compound that inhibits cellular proliferation, Paclitaxel, Rapamycin, Sirolimus, Actinomycin D, Methotrexate, Doxorubicin, cyclophosphamide, and 5-fluorouracil, and combinations thereof.

12. An apparatus as recited in claim 1 further comprising a plurality of therapeutic agents or medicaments coated on at least a portion of said expansion member.

13. An apparatus as recited in claim 1, further comprising a lumen extending throughout the longitudinal length of said catheter, said lumen having a distal end that terminates within said expansion member, said lumen capable of delivering a medicament.

14. 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;

one or more electrical leads extending throughout the longitudinal length of said catheter and engaged to said expansion member; and

a medicament coated on said expansion member.

15. An apparatus as recited in claim 14 wherein said expansion member defines a flow passageway extending between said first end and said second end of the expansion member.

16. An apparatus as recited in claim 14 wherein said expansion member comprises a first plurality of flexible elongate elements helically wound in a first direction of rotation and a second plurality of flexible elongate elements helically wound in a second direction of rotation to form a braid.

17. An apparatus as recited in claim 14 wherein said expansion member is adapted to allow blood perfusion while said expansion member in either in said first diameter or in said second diameter.

18. An apparatus as recited in claim 14 wherein said therapeutic agent or medicament is incorporated into a non-therapeutic substrate.

19. An apparatus as recited in claim 14, wherein said therapeutic agent or 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.

20. An apparatus as recited in claim 14, wherein said therapeutic agent or 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.

21. An apparatus as recited in claim 14, wherein said therapeutic agent or 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, 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.

22. An apparatus as recited in claim 14, wherein said therapeutic agent or 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.

23. An apparatus as recited in claim 14, wherein said therapeutic agent or 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.

24. An apparatus as recited in claim 14, wherein said therapeutic agent or medicament is a compound that inhibits cellular proliferation, Paclitaxel, Rapamycin, Sirolimus, Actinomycin D, Methotrexate, Doxorubicin, cyclophosphamide, and 5-fluorouracil, and combinations thereof.

25. An apparatus as recited in claim 14, further comprising a lumen extending throughout the longitudinal length of said catheter, said lumen having a distal end that terminates within said expansion member, said lumen capable of delivering a medicament.

26. An apparatus as recited in claim 14, further comprising a plurality of therapeutic agents or medicaments coated on at least a portion of said expansion member.

27. An apparatus as recited in claim 14, wherein said electrical leads can communicate electrical energy to said expansion member to compel said medicament or therapeutic agent into target tissues by iontophoretic means.

28. An apparatus as recited in claim 14, wherein said electrical leads can communicate electrical energy to said expansion member to compel electroporation transfer of said medicament or therapeutic agent into target tissues.

29. An apparatus as recited in claim 14, wherein said electrical leads can communicate electrical energy to said expansion member to cause both iontophoretic and electroporation transfer of said medicament or therapeutic agent into target tissues.

30. An apparatus as recited in claim 14, wherein said electrical leads can communicate electrical energy to said expansion member to cause said medicament or therapeutic agent to electrically bond to said expansion member.

31. 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 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 medicament while allowing blood or bodily fluids to flow through said expandable mesh.

32. A method for dilating and delivering a medicament to an obstruction in a body passageway which comprises the steps of:

advancing a mechanical dilatation catheter to a predetermined site with a body passageway, said catheter having an substantially cylindrical expansion member coated with a medicament, said expansion member being moveable between a first contracted configuration wherein said expansion member is defined by a first dimension extending in a radial direction, and a second expanded configuration wherein said member is defined by a second dimension extending in said radial direction;

applying a force on said coated expansion member in an axial direction to move said expansion member between said first contracted configuration to said second expanded configuration wherein said expansion member dilates said obstruction or body passageway and delivers the medicament to an said obstruction or body passageway.

33. A method as recited in claim 32 which further comprises the step of positioning a guidewire in the body passageway, and wherein said advancing step is accomplished by threading said expansion member over said guidewire.

34. A method as recited in claim 32 which further comprises the step of allowing said expansion member to be in said second expanded configuration for a predetermined period of time after the dilatation step to further expose said obstruction to the medicament.

35. A method for dilating and delivering a medicament to an obstruction in a body passageway which comprises the steps of:

advancing a mechanical dilatation catheter to a predetermined site with a body passageway, said catheter having an expansion member coated with a medicament and a iontophoretic transport means, said expansion member being moveable between a first contracted configuration wherein said member is defined by a first dimension extending in a radial direction, and a second expanded configuration wherein said member is defined by a second dimension extending in said radial direction;

applying a force on said expansion member in an axial direction to move said expansion member between said first contracted configuration to said second expanded configuration wherein said obstruction is dilated;

supplying a flow of electrical current to said iontophoretic means to deliver said medicament into said obstruction or body passageway.

36. A method as recited in claim 35 which further comprises the step of positioning a guidewire in the body passageway, and wherein said advancing step is accomplished by threading said catheter over said guidewire.

37. A method as recited in claim 35 which further comprises the step of allowing said expansion member to be in said second expanded configuration for a predetermined period of time after the dilatation step to further expose said obstruction to the medicament.

38. A method as recited in claim 35 which further comprises the step of varying the electric current with time to provide a waveform that controls the rate of iontophoretic transport of said medicament.

39. A method as recited in claim 35, further comprising, prior to advancing the catheter, the step of applying electrical energy to said expansion member to cause said medicament or therapeutic agent to electrically bond to said expansion member.

40. A method for dilating and delivering a medicament to an obstruction in a body passageway which comprises the steps of:

advancing a mechanical dilatation catheter to a predetermined site with a body passageway, said catheter having an expansion member coated with a medicament and a electroporation transport means, said expansion member being moveable between a first contracted configuration wherein said member is defined by a first dimension extending in a radial direction, and a second expanded configuration wherein said member is defined by a second dimension extending in said radial direction;

applying a force on said expansion member in an axial direction to move said expansion member between said first contracted configuration to said second expanded configuration wherein said obstruction is dilated;

supplying a flow of electrical current to said electroporation means to deliver said medicament into said obstruction or body passageway.

41. A method as recited in claim 40 which further comprises the step of positioning a guidewire in the body passageway, and wherein said advancing step is accomplished by threading said catheter over said guidewire.

42. A method as recited in claim 40 which further comprises the step of allowing said expansion member to be in said second expanded configuration for a predetermined period of time after the dilatation step to further expose said obstruction to the medicament.

43. A method as recited in claim 40 which further comprises the step of varying the electric current with time to provide a waveform that controls the rate of electroporation transport of said medicament.

44. A method as recited in claim 40, further comprising, prior to advancing the catheter, the step of applying electrical energy to said expansion member to cause said medicament or therapeutic agent to electrically bond to said expansion member.