Use of angiogenic lipids for vascularizing tissue

• US 5,756,453 A
• Filed: 01/31/1996
• Issued: 05/26/1998
• Est. Priority Date: 08/03/1994
• Status: Expired due to Fees

• Current Assignee: Cell Therapeutics, Inc.
• Original Assignee: Cell Therapeutics, Inc.
• Inventors: Nudelman, Edward D., Vedder, Nicholas B.
• Primary Examiner(s): Lilling, Herbert J.
• Application Number:
  US08/593,320
• Time in Patent Office: 846 Days
• Field of Search: 435/1.2, 514/547, 514/2, 514/11, 514/450, 514/285, 514/215, 514/284, 514/247, 514/291, 623/1, 623/11, 623/13, 424/422, 424/424, 554/223
• US Class Current: 514/15.4
• 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 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/075 Ethers or acetals
• CPC Class Codes: A61K 31/08 acyclic, e.g. paraformaldehyde
• CPC Class Codes: A61K 31/121 acyclic
• CPC Class Codes: A61K 31/23 of acids having a carboxyl group bound to a chain of seven or more carbon atoms
• CPC Class Codes: A61K 31/231 having one or two double bonds
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

There is disclosed a method for vascularizing tissue, a method for improving vascularization of ischemic tissue, and a method for improving the viability of grafted tissue or tissue survival in gradient ischemia of heart, brain or skin, comprising administering locally to the grafted or ischemic tissue or the site of the graft an effective amount of a compound comprising an alk-1-enyl glycerol derivative.

Claims

1. A method for vascularizing tissue, comprising administering to the grafted tissue or the site of the graft an effective amount of a compound comprising an alk-1-enyl glycerol derivative having the formula:

##STR5## wherein R is a straight or branched C_1-24 alkyl or a straight or branched C_1-24 acyl and X and Y each is H or an acyl group having from 2 to 26 carbon atoms.

2. The method of claim 1 wherein R is C₁₄ or C₁₆ acyl, X is an acyl group and Y is H.

3. The method of claim 1 wherein the tissue is grafted from self or a donor.

4. The method of claim 1 wherein the compound further comprises an immunosuppressively effective amount of an immunosuppressive compound.

5. The method of claim 4 wherein the immunosuppressive compound is selected from the group consisting of cyclosporin A, cyclosporin G, mycophenolic acid morpholinoethylester, rapamycin, FK506, brequinar, and glucocorticosteroids.

6. A method for improving vascularization of ischemic tissue, comprising administering to the ischemic tissue or the site of the ischemia an effective amount of a compound comprising an alk-1-enyl glycerol derivative having the formula:

##STR6## wherein R is a straight or branched C_1-24 alkyl or a straight or branched C_1-24 acyl and X and Y each is H or an acyl group having from 2 to 26 carbon atoms.

7. The method of claim 6 wherein R is C₁₄ or C₂₆ acyl, X is an acyl group and Y is H.

8. The method of claim 6 wherein the ischemic tissue is selected from the group consisting of myocardium, brain, liver, bowel, kidney, muscle and skin.

9. A method for improving the viability of grafted tissue or flap survival in gradient ischemia, comprising administering locally to the grafted tissue or the site of the graft an effective amount of a compound comprising an alk-1-enyl glycerol derivative having the formula:

##STR7## wherein R is a straight or branched C_1-24 alkyl or a straight or branched C_1-24 acyl and X and Y each is H or an acyl group having from 2 to 26 carbon atoms.

10. The method of claim 9 wherein R is C₁₄ or C₁₆ acyl, X is an acyl group and Y is H.

11. The method of claim 9 wherein the tissue is grafted from self or a donor.

12. The method of claim 9 wherein the compound further comprises an immunosuppressively effective amount of an immunosuppressive compound.

13. The method of claim 12 wherein the immunosuppressive compound is selected from the group consisting of cyclosporin A, cyclosporin G, mycophenolic acid morpholinoethylester, rapamycin, FK506, brequinar, and glucocorticosteroids.