Periodic constriction of vessels to treat ischemic tissue

• US 6,544,543 B1
• Filed: 12/27/2000
• Issued: 04/08/2003
• Est. Priority Date: 12/27/2000
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Roorda, Wouter E., Mandrusov, Evgenia, Buchko, Christopher J.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Bennett, Rachel M.
• Application Number:
  US09/752,399
• Time in Patent Office: 832 Days
• Field of Search: 424/422, 424/423, 424/489
• US Class Current: 424/422
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: A61K 47/665 the pre-targeting system, clearing therapy or rescue therapy involving biotin-(strept) avidin systems
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61L 2300/40 characterised by a specific therapeutic activity or mode of action
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 37/0092 : using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Brief periods of occlusion of blood flow in an otherwise open target vessel adjacent to vessels supplying blood to an ischemic region are caused by periodic administration of a therapeutically effective amount of a vasoconstrictor. It is anticipated these brief periods of occlusion will induce the enlargement of collateral vessels, causing increased blood flow to the ischemic region.

Claims

1. A method for treating ischemia in a patient, the method comprising:

depositing a layer of polymer on the luminal surface of a target vessel; and

injecting microspheres containing a vasoconstrictor into the patient, wherein the microspheres are adapted to attach to the layer of polymer and release the vasoconstrictor in situ adjacent to the layer of polymer.

2. The method of claim 1, wherein the vasoconstrictor is administered to the target vessel for a period of time between thirty seconds and two minutes, at least four times a day, for at least 5 days.

3. The method of claim 1, wherein the vasoconstrictor is selected from the group consisting of epinephrine, norepinephrine, lysine vasopressin, 8-arginine vasopressin, angiotensin II, methoxamine hydrochloride, and analogs thereof.

4. The method of claim 1, wherein the layer of polymer and the microspheres include first members of an affinity pair;

and

further comprising injecting receptor molecules into the patient, the receptor molecules comprising second members of the affinity pair, wherein the second members of the receptor molecules are adapted to engage the first members of the layer of polymer and the microspheres so that the microspheres attach to the layer of polymer.

5. The method of claim 4, wherein the first member of the affinity pair is selected from the group consisting of biotin and analogs thereof and further wherein the second member of the affinity pair is selected from the group consisting of avidin and analogs thereof.

6. The method of claim 1, wherein the layer of polymer includes first members of an affinity pair, and the microspheres include second members of an affinity pair.

7. The method of claim 1, wherein the first members of the affinity pair are selected from the group consisting of biotin and analogs thereof and the second members of the affinity pair are selected from the group consisting of avidin and analogs thereof.

8. The method of claim 1, further comprising:

providing energy from an external energy source to rupture the microspheres, thereby releasing the vasoconstrictor.

9. The method of claim 8, wherein the energy is an ultrasound beam.

10. The method of claim 1, wherein the microspheres are comprised of a material selected from the group consisting of poly(DL Lactide-co-Glycolide), poly-lactic acid, polyglycolic acid, gelatin, polyester, alginate, polyethylene oxide, lipid, gas-filled liposomes, and albumin.

11. The method of claim 1, wherein the layer of polymer is selected from the group consisting of poly-lactic acid, poly-glycolic acid, polyphosphazenes, polyhydroxybutyric acid, poly-caprolactone, polyanhydrides, polyethylene glycol, and copolymers and mixtures thereof.

12. The method of claim 1, wherein the layer of polymer is deposited using a stent.

13. The method of claim 1, wherein the layer of polymer is deposited by paving the endoluminal surface of the target vessel with a hydrogel.

14. The method of claim 1, wherein the polymer or microspheres are biotinylated using photoactivatable biotin.

15. The method of claim 1, wherein the act of depositing a polymer comprises applying a hydrogel precursory to the target vessel and causing the polymerization of the precursor to form the layer.