Compositions and methods for neovascularization

• US 9,446,031 B2
• Filed: 01/16/2013
• Issued: 09/20/2016
• Est. Priority Date: 01/18/2012
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, National University of Singapore
• Original Assignee: Massachusetts Institute of Technology, National University of Singapore
• Inventors: Raghunath, Michael, Lim, Sei Hien, Kamm, Roger Dale
• Primary Examiner(s): Soroush, Layla
• Application Number:
  US13/743,223
• Publication Number:
  US 20130197038A1
• Time in Patent Office: 1,343 Days
• Field of Search: 514/350
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/688 both hydroxy compounds having nitrogen atoms, e.g. sphingomyelins
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 5/06 Animal cells or tissues; Human cells or tissues preservation of living cells or tissues A01N1/02
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells

Abstract

The invention is directed to a method of inducing angiogenesis at a site in an individual in need thereof comprising administering locally to the site an effective amount of one or more agents that induce hypoxia induced factor 1α (HIF-1α). In another aspect, the invention is directed to a method of inducing angiogenesis at a site in an individual in need thereof comprising administering locally to the site an effective amount of one or more agents that induce hypoxia induced factor 1α (HIF-1α) and one or more lysophospholipids. In addition, the invention is directed to methods of generating prevascularized tissue, methods of generating a vascular network in a device and compositions thereof.

Claims

1. A method of inducing angiogenesis at a site in an individual in need thereof comprising administering locally to the site an effective amount of ciclopirox olamine (CPX) and sphingosine 1-phosphate (S1P).

2. The method of claim 1 wherein the CPX and S1P are present in a biocompatible matrix that is administered locally to the site.

3. The method of claim 1 wherein the CPX and S1P are administered with one or more cell types that support and maintain functional blood vessels.

4. The method of claim 1 wherein the site in the individual is a wound, a graft, a prosthetic device, a suture, an area of malperfusion, an infarcted area, a bone fracture, an area of non-union in bone, an area at or near an implant or sensor.