Claims for Patent: 5,709,874

Summary for Patent: 5,709,874

Title:	Device for local drug delivery and methods for using the same
Abstract:	A device for the local delivery of a substance into a natural tissue conduit in the mammalian body. The device has a substance delivery segment which provides a means for locally delivering a substance into the boundary layer of fluid flowing through the conduit without disrupting the fluid flow therethrough. For example, an indwelling catheter is provided for endovascular delivery of a substance locally to a targeted treatment area. Also provided are methods of locally delivering a substance into a natural tissue conduit in the mammalian body utilizing the device of the present invention.
Inventor(s):	Hanson; Stephen R. (Stone Mountain, GA), Scott; Neal A. (Atlanta, GA), King, III; Spencer B. (Atlanta, GA), Harker; Laurence A. (Atlanta, GA)
Assignee:	Emory University (Atlanta, GA)
Application Number:	08/660,203
Patent Claims:	1. A device for the local delivery of a substance at a predetermined site in a natural tissue conduit in the mammalian body, the conduit having a luminal surface defining a lumen, comprising: a) an elongated flexible tube of a preselected length and diameter having an external surface, a proximal end, an opposite distal end, and a lumen extending longitudinally therethrough interconnecting the proximal and distal ends with the proximal end defining an opening therethrough, the tube having a substance delivery segment adjacent the distal end and defining a plurality of substance delivery holes through the external surface which are in fluid communication with the lumen of the tube, the substance delivery segment being moveable among a first rest position wherein it has a first shape, a second position wherein it has a second shape, and a third operative position wherein it has a third shape, the third position being intermediate the first and second positions; b) means for moving the substance delivery segment from its first position to its second position, the substance delivery segment tending to return to the first position when the moving means is no longer applied to the substance delivery segment; and c) means for introducing the substance into the lumen of the tube for delivery into the natural tissue conduit. 2. A method for providing prolonged localized delivery of a biologically active substance directly into the boundary layer of blood flowing through a predetermined site within a blood vessel without substantially compromising central blood flow through the vessel, the blood vessel having a luminal surface defining a lumen, comprising the steps of: a) placing a substance delivery device that is adapted to provide prolonged localized delivery of a therapeutic agent directly into the boundary layer of blood flowing through a predetermined site without substantially compromising central blood flow through the vessel in the lumen of the blood vessel adjacent the predetermined site; and b) delivering a substance to the predetermined site via the substance delivery device. 3. The method of claim 2, wherein the substance delivery device is the device of claim 1. 4. The method of claim 2, wherein the substance delivery device is the device of claim 1. 5. The method of claim 2, wherein the substance is a therapeutically effective amount of a drug. 6. The method of claim 2, wherein the predetermined site is an angioplasty site. 7. The method of claim 2, wherein the predetermined site is the boundary layer of blood flowing through the blood vessel upstream of a target treatment area. 8. The method of claim 2, wherein the substance is a therapeutically effective amount of a drug. 9. The method of claim 2, wherein the substance is a therapeutically effective amount of an anticoagulant. 10. The method of claim 9, wherein the anticoagulant is selected from the group consisting of heparin, hirudin, hirulog, hirugen, activated and non-activated protein C, synthetic antagonism of thrombin, Factor VIIa, Factor Xa and activated and non-activated coagulation factors. 11. The method of claim 2, wherein the substance, in a therapeutically effective amount, antagonizes platelet deposition and thrombus formation. 12. The method of claim 11, wherein the substance is selected from the group consisting of: plasmin, tissue plasminogen activator (tPA), urokinase (UK), single chain prourokinase (scuPA), streptokinase; prostaglandins, cyclooxygenase inhibitors, phosphodiesterase inhibitors, thromboxane synthetase inhibitors; antagonists of glycoprotein receptors including (GP) Ib,GP IIb/IIIa, antagonists of collagen receptors, and antagonists of platelet thrombin receptors. 13. The method of claim 2, wherein the substance, in a therapeutically effective amount, affects platelet metabolic function. 14. The method of claim 13, wherein the substance is selected from the group consisting of prostaglandins, cyclooxygenase inhibitors, phosphodiesterase inhibitors, thromboxane inhibitors, inhibitors of calcium transport, and cyclic AMP agonists. 15. The method of claim 2, wherein the substance, in a therapeutically effective amount, prevents restenosis in a blood vessel. 16. The method of claim 15, wherein the substance is selected from the group consisting of a growth factor, a growth factor inhibitor, growth factor receptor antagonist, transcriptional repressor, translational repressor, antisense DNA, antisense RNA, replication inhibitor, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules comprising a growth factor and a cytotoxin, and bifunctional molecules comprising an antibody and a cytotoxin. 17. The method of claim 2, wherein the substance is a therapeutically effective amount of vasodilator. 18. The method of claim 17, wherein the substance is selected from the group consisting of nitroglycerin, nitroprusside, agents which liberate nitric oxide, and agents which inhibit calcium transport. 19. The device of claim 1, wherein the substance delivery segment assumes the third position when the moving means is no longer applied thereto, such that the substance delivery segment is capable of exerting a force against the luminal surface of the conduit in the third position sufficient to anchor the substance delivery segment at the predetermined site within the lumen of a natural tissue conduit. 20. The device of claim 1, wherein the first shape comprises a plurality of spiral turns of the substance delivery segment about the longitudinal axis of the device such that the substance delivery segment forms a hollow coil having a first predetermined diameter. 21. The device of claim 20, wherein the substance delivery holes are at a preselected location on the coil. 22. The device of claim 1, wherein the third shape comprises a plurality of spiral turns of the substance delivery segment about the longitudinal axis of the device such that the substance delivery segment forms a hollow coil having a second predetermined diameter. 23. The device of claim 22, wherein the substance delivery holes are at a preselected location on the coil. 24. The device of claim 23, wherein the preselected location of the substance delivery holes is that the holes are juxtaposed to the luminal surface of the conduit such that a substance delivered therethrough directly contacts the luminal surface of the tissue conduit. 25. The device of claim 23, wherein the preselected location of the substance delivery holes is that the holes are adjacent to the luminal surface of the conduit such that a substance delivered therethrough is delivered into the natural tissue conduit adjacent the luminal surface thereof. 26. The device of claim 23, wherein the preselected location of the substance delivery holes is that the holes are opposite a portion of the external surface of the substance delivery segment which contacts the luminal surface of the conduit such that a substance delivered therethrough is delivered into the boundary layer of a fluid flowing through the lumen of the natural tissue conduit. 27. The device of claim 1, wherein the distal end of the tube further defines an opening therethrough which is in fluid communication with the lumen of the tube and the opening defined by the proximal end thereof. 28. The device of claim 27, wherein the substance delivery segment is substantially linear in the second position and the moving means comprises a guidewire having a distal tip which is removably insertable into the proximal opening of the lumen of the tube and through the opening of the distal end thereof, the guidewire being sufficiently stiff to maintain the substance delivery segment in the second position, thereby allowing deployment of the substance delivery segment through the conduit to the predetermined site. 29. The device of claim 1, wherein the proximal opening of the lumen of the tube is moveable between a closed position which forms a fluid tight seal and an open position which allows a guidewire to pass therethrough. 30. The device of claim 27, wherein the distal opening of the lumen of the tube is moveable between a closed position which forms a fluid tight seal and an open position which allows a guidewire to pass therethrough. 31. The device of claim 1, wherein the distal end of the tube forms a fluid tight seal of the lumen of the tube and the device further comprises a guidewire having a distal tip and a proximal anchoring end, the guidewire being mounted in the tube at the distal end thereof for guiding the tube through the lumen of the natural tissue conduit to the predetermined site. 32. The device of claim 31, wherein the substance delivery segment is substantially linear in the second position and the moving means comprises a stylette having a distal tip which is removably insertable into the proximal opening of the lumen of the tube, through the lumen of the tube to the distal end thereof, the stylette being sufficiently stiff to maintain the substance delivery segment in the second position, thereby allowing deployment of the substance delivery segment through the conduit to the predetermined site. 33. The device of claim 1, wherein the substance delivery segment is comprised of a resilient biocompatible material selected from the group consisting of polymer, synthetic rubber, natural rubber, metal and plastic preformed to into the first shape such that the substance delivery segment normally rests in the first position. 34. The device of claim 33, wherein the material is a non-biodegradable polymer selected from the group consisting of polyurethane, polyethylene, polyethylene terephthalate, polytetrafluoroethylene, ethylene vinyl acetate, polyimid, and nylon. 35. The device of claim 33, wherein the material is a biodegradable polymer selected from the group consisting of polylactic acid and polyglycolic acid. 36. The device claim 33, wherein the material is a metal selected from the group consisting of stainless steel, and tantalum, platinum and nitinol. 37. The device claim 36, wherein the metal is nitinol and wherein the moving means comprises exposing the nitinol to a fluid having a temperature of between about 40.degree.-65.degree. C. 38. The device claim 37, wherein the metal is nitinol and wherein the moving means comprises exposing the nitinol to a fluid having a temperature of about 55.degree. C. 39. The device of claim 37, wherein the fluid is selected from the group consisting of ringer's solution, lactated ringer's solution, 5% dextrose solution, 10% dextrose solution, normal saline solution, 1/2 normal saline solution, 5% dextrose and 1/2 normal saline solution, and sterile water. 40. The device of claim 1, further comprising a semi-permeable membrane covering the external surface of the substance delivery segment and the substance delivery holes defined therein such that delivery of a substance through the substance delivery holes to the predetermined site occurs at a preselected rate. 41. The device of claim 40, wherein the semi-permeable membrane is comprised of a biocompatible material selected from the group consisting of a biodegradable polymer and a non-biodegradable polymer. 42. The device of claim 41, wherein the semi-permeable membrane is a non-biodegradable polymer selected from the group consisting of polytetrafluoroethylene, ethylene vinyl acetate, polyethylene, and polyethylene terephthalate. 43. The device of claim 40, wherein the substance is a fluid and the preselected rate is between about 0.01 and 1.0 ml/minute. 44. The device of claim 1, wherein the substance introducing means comprises an infusion port attached to the tube adjacent the proximal end which is in fluid communication with the lumen of the tube such that a substance can be delivered through the port and into the lumen of the natural tissue conduit. 45. The device of claim 1, further comprising at least one opening through the external surface of the tube which is in fluid communication with the lumen of the tube, the opening being located between the substance delivery segment and the proximal end of the tube such that at least a portion of a substance delivered into the lumen of the tube can pass into the natural tissue conduit through said opening. 46. The device of claim 1, wherein the conduit is a blood vessel. 47. The device of claim 1, wherein the substance is a drug. 48. A device for the local delivery of a biologically active substance at a predetermined site in a natural tissue conduit in the mammalian body, the conduit having a luminal surface defining a lumen, comprising: a) an elongated flexible tube of a preselected length and diameter having an external surface, a proximal end, an opposite distal end, and a lumen extending longitudinally therethrough interconnecting the proximal and distal ends with the proximal end defining an opening therethrough, the tube having a substance delivery segment adjacent the distal end and defining a plurality of substance delivery holes through the external surface which are in fluid communication with the lumen of the tube, the substance delivery segment being movable between a resting shape wherein the substance delivery segment comprises a plurality of spiral turns about the longitudinal axis of the device such that the substance delivery segment forms a hollow coil having a first resting diameter and an operative shape wherein the substance delivery segment comprises a plurality of spiral turns about the longitudinal axis of the device such that the substance delivery segment forms a hollow coil having a second operative diameter; and, b) means for introducing the substance into the lumen of the tube for delivery into the natural tissue conduit.

Details for Patent 5,709,874

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2013-04-14
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2013-04-14