Polymer coated device for electrically mediated drug delivery

• US 20040220511A1
• Filed: 04/29/2003
• Published: 11/04/2004
• Est. Priority Date: 04/29/2003
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Burkoth, Terry L., Segal, Jerome, Scott, Neal, Shih, Lih-Bin
• Granted Patent: US 7,517,342 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428

Abstract

The present invention relates to a catheter with an expandable distal end for delivering one or more medicaments. The catheter is manufactured with materials of construction that allow the transfer of electrical energy from the proximal end of the catheter to the distal expandable end. The catheter also has a means for controlling or manipulating the expandable distal end to expand and contract into various configurations. The distal end of the catheter is processed by a specific method of manufacturing whereby the expandable distal end is coated with one or more layers of a hydrogel copolymer wherein at least one layer of which coating encapsulates one or more medicaments and zero or more charged carriers to facilitate the electrophoretic and electro-osmostic mobilities of the medicaments.

Claims

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

a catheter with an expandable distal end;

a means for delivering electrical energy from a proximal end to said expandable distal end, and;

said distal end incorporating a hydrogel polymer encapsulated with one or more medicaments and zero or more electrophoretic or electro-osmotic carriers.

2. An apparatus as recited in claim 1, wherein said catheter with hydrogel encapsulating a therapeutic agent or medicament will function to release the medicaments from the hydrogel by electrophoretic, iontophoretic or electro-osmotic means.

3. An apparatus as recited in claim 1, wherein said catheter with hydrogel encapsulating a therapeutic agent or medicament will function to deliver the medicaments into target tissues of said vascular segment or body passageway by electrophoretic, iontophoretic or electro-osmotic means.

4. An apparatus as recited in claim 1, wherein said hydrogel encapsulated 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, a tissue factor inhibitor, and a tick anti-platelet peptide, and combinations thereof.

5. An apparatus as recited in claim 1, wherein said hydrogel encapsulated agent or medicament is a promoter of vascular cell growth selected from the group consisting of a growth factor stimulator, a growth factor receptor.

6. An apparatus as recited in claim 1, wherein said hydrogel encapsulated 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, 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, a single-stranded DNA molecule, a double-stranded DNA molecule, a single-stranded RNA molecule, a double-stranded RNA molecule, and combinations thereof.

7. An apparatus as recited in claim 1, wherein said hydrogel encapsulated 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.

8. An apparatus as recited in claim 1, wherein said hydrogel encapsulated 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, a growth factor receptor antagonist, an immunosuppressive agent, a steroid such as estrogen, hydrocortisone or dexamethasone, and a protein kinase inhibitor, and combinations thereof.

9. An apparatus as recited in claim 1, wherein said hydrogel encapsulated agent or 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, alcohol, arsenic trioxide, bleomycin, captothecin, capecitabine, carmustine, celecoxib, daunorubucin, docetaxel, etoposide, exemestane, fludarabine, gemcitabine, hydroxyurea, idarubicin, irinotecan, ifosfamide, letrozole, leucovorin, mitoxantrone, pamidronate, pentostatin, porfirmer sodium, streptozotocin, tamoxifen, temozolamide, tenopside, topotecantoremifene, tretinoin, valrubicin, vinorelbine, zoledronate, altretamine, anastrozole, bexarotene, carboplatin, everolimus, chlorambucil, busulfan, and any other drug that can inhibit cell proliferation, and combinations thereof.

10. An apparatus as recited in claim 1, wherein said hydrogel encapsulated agent or medicament will migrate into target tissues when exposed to an electrical energy applied by an electrical delivery device.

11. An apparatus as recited in claim 1, wherein said hydrogel encapsulated agent or medicament is a combination of one or more medicaments.

12. An apparatus as recited in claim 1, wherein said catheter with hydrogel encapsulating a therapeutic agent or medicament is an over-the wire design.

13. An apparatus as recited in claim 1, wherein said catheter with hydrogel encapsulating a therapeutic agent or medicament employs a rapid exchange design.

14. An apparatus as recited in claim 1 further comprised by a first contracted configuration and a second expanded configuration wherein said expandable distal end is adapted to allow blood perfusion while said expandable distal is in either in said first contracted configuration or in said second expanded configuration.

15. A method for introducing encapsulated medicaments into cells of a patient, comprising the steps of:

selecting a elongated catheter a substantially cylindrical shaped expansion member located on a distal end, 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 hydrogel encapsulated medicament coated on at least a portion of said expansion member;

locating said catheter into a selected blood vessel or sytrcture of a patient;

expanding said cylindrical expansion member wherein a portion of said cylindrical expansion member contacts the vessel wall at a predetermine location;

applying a predetermined electric signal to said expansion member to assist in transporting said encapsulated medicaments across cell membranes.

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

advancing a polymer coated device for electrically mediated drug delivery 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 encapsulated medicament to an said obstruction or body passageway.

17. A method as recited in claim 16 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.

18. A method as recited in claim 16 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.

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

advancing a polymer coated device for a electrically mediated drug delivery to a predetermined site within a body passageway, said device having an expansion member coated with a hydrogel liposome or micelle encapsulated medicament and a electrical 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 electrical transport means to deliver to said liposome or micelle-encapsulated medicament into said obstruction or body passageway.

20. A method as recited in claim 19 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.

21. A method as recited in claim 19 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.

22. A method as recited in claim 19 which further comprises the step of varying the electric current with time to provide a waveform that controls the rate of eletrical transport of said medicament.

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

a catheter with an expandable mechanical distal end;

a means for delivering electrical energy from a proximal end to said expandable distal end, and;

said distal end incorporating a hydrogel polymer encapsulated with one or more medicaments.

24. An apparatus as recited in claim 23, wherein said catheter with hydrogel encapsulating a therapeutic agent or medicament will function to release the medicaments from the hydrogel by electrophoretic, iontophoretic or electro-osmotic means.

25. An apparatus as recited in claim 23, wherein said catheter with hydrogel encapsulating a therapeutic agent or medicament will function to deliver the medicaments into target tissues of said vascular segment or body passageway by electrophoretic, iontophoretic or electro-osmotic means.

26. An apparatus as recited in claim 23, wherein said hydrogel encapsulated 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, a tissue factor inhibitor, and a tick anti-platelet peptide, and combinations thereof.

27. An apparatus as recited in claim 23, wherein said hydrogel encapsulated agent or medicament is a promoter of vascular cell growth selected from the group consisting of a growth factor stimulator, a growth factor receptor.

28. An apparatus as recited in claim 23, wherein said hydrogel encapsulated 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, 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, a single-stranded DNA molecule, a double-stranded DNA molecule, a single-stranded RNA molecule, a double-stranded RNA molecule, and combinations thereof.

29. An apparatus as recited in claim 23, wherein said hydrogel encapsulated 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.

30. An apparatus as recited in claim 23, wherein said hydrogel encapsulated 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, a growth factor receptor antagonist, an immunosuppressive agent, a steroid such as estrogen, hydrocortisone or dexamethasone, and a protein kinase inhibitor, and combinations thereof.

31. An apparatus as recited in claim 23, wherein said hydrogel encapsulated agent or 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, alcohol, arsenic trioxide, bleomycin, captothecin, capecitabine, carmustine, celecoxib, daunorubucin, docetaxel, etoposide, exemestane, fludarabine, gemcitabine, hydroxyurea, idarubicin, irinotecan, ifosfamide, letrozole, leucovorin, mitoxantrone, pamidronate, pentostatin, porfirmer sodium, streptozotocin, tamoxifen, temozolamide, tenopside, topotecantoremifene, tretinoin, valrubicin, vinorelbine, zoledronate, altretamine, anastrozole, bexarotene, carboplatin, everolimus, chlorambucil, busulfan, and any other drug that can inhibit cell proliferation, and combinations thereof.

32. An apparatus as recited in claim 23, wherein said hydrogel encapsulated agent or medicament will migrate into target tissues when exposed to an electrical energy applied by an electrical delivery device.

33. An apparatus as recited in claim 23, wherein said hydrogel encapsulated agent or medicament is a combination of one or more medicaments.

34. An apparatus as recited in claim 23, wherein said catheter with hydrogel encapsulating a therapeutic agent or medicament is an over-the wire design.

35. An apparatus as recited in claim 23, wherein said catheter with hydrogel encapsulating a therapeutic agent or medicament employs a rapid exchange design.

36. An apparatus as recited in claim 23 further comprised by a first contracted configuration and a second expanded configuration wherein said expandable distal end is adapted to allow blood perfusion while said expandable distal is either in said first contracted configuration or in said second expanded configuration.