Angiogenic lipid formulations

• US 5,798,386 A
• Filed: 03/04/1996
• Issued: 08/25/1998
• 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.
• Primary Examiner(s): Lilling, Herbert J.
• Application Number:
  US08/611,980
• Time in Patent Office: 904 Days
• Field of Search: 554/223, 554/227, 514/547, 514/549, 514/723
• US Class Current: 514/547
• 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 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• 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 an aqueous formulation for vascularizing ischemic or grafted tissue, comprising an alk-1-enyl glycerol derivative having the formula: ##STR1## wherein R is a straight or branched C_1-24 saturated or unsaturated alkyl or a straight or branched C_1-24 aryl and X and Y each is H or an saturated or unsaturated alkyl group having from 2 to 26 carbon atoms, or a monoglyceride having a C_1-24 ether-linked saturated alkyl in an aqueous buffered pharmaceutical carrier.

Claims

1. An aqueous formulation for vascularizing ischemic or grafted tissue, comprising a glycerol derivative having the following formula:

##STR6## wherein R is a straight or branched C_1-24 saturated or unsaturated alkyl or a straight or branched C_1-24 aryl;

P_n is --CH═

HC--;

n is 0 to 1, with the proviso that when n is 0, R is C_6-24, and X and Y are each independently H or an aryl or alkyl group having from 2 to 26 carbon atoms, or a monoglyceride having a C_8-24 ether-linked saturated alkyl in an aqueous buffered pharmaceutical carrier.

2. The aqueous formulation of claim 1 wherein R is C₁₄ or C₁₆ saturated or unsaturated alkyl, X is a saturated or unsaturated alkyl group and Y is H.

3. The aqueous formulation of claim 1 R is a C₁₆ monounsaturated alkyl.

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

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

6. The aqueous formulation of claim 1 wherein the aqueous formulation further comprises an emulsifying concentration of phosphotidylinositol.

7. The aqueous formulation of claim 6 wherein the concentration of phosphotidylinositol is from about 0.5 mM to about 10 Mm.

8. An aqueous formulation of claim 1 wherein X and Y are both hydrogen, n is 1 and R is C₁₆ aryl.

9. An aqueous formulation of claim 8 further comprising an emulsifying agent.

10. The aqueous formulation of claim 4 wherein R is a C₁₈ alkyl and n is 0.