Use of 13-hode as a regulator of vascular biocompatibility and an inhibitor of cell hyperplasia

Abstract

This invention relates to the regulation of vascular endothelium biocompatibility and to the inhibition of vessel wall cell and other types of cell hyperplasia following vessel wall dysfunction and/or injury More particularly, the invention relates to the dietetic and pharmaceutical preparations of 13-hydroxyoctadeca-9Z, 11E-dienoic acid (13-HODE) and its use in reducing or inhibiting vessel wall hyperplasia and restoring vessel wall biocompatibility.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:  
     
         1 . A method of reducing or inhibiting cell hyperplasia and restoring vessel wall biocompatibility in a mammal or human in need of such treatment comprising administering orally an amount of 13-hydroxyoctadeca-9Z, 11E-dienoic acid (13-HODE) effective to reduce or inhibit vessel wall thrombogenicity where the 13-HODE is administered as a pharmaceutical composition comprising 13-HODE and a carrier comprising either a mono- di- or triglyceride oil, or an ester of a fatty acid containing 16-26 carbon atoms and one or more double bonds.  
     
     
         2 . The method of  claim 1  wherein the carrier is selected from the group consisting of corn, sunflower, safflower, cottonseed, grape seed, olive, evening primrose, borage, fish body and fish liver oils.  
     
     
         3 . The method of  claim 1 , wherein the carrier is selected from the group of ethyl esters of the following fatty acids: eicosapentaenoic, oleic, linoleic, alpha-linolenic, stearidonic, gamma-linolenic, dihomogammalinolenic, arachidonic, docosapentaenoic and docosahexaenoic.  
     
     
         4 . The method of  claim 1 , wherein the composition further comprises a fat-soluble antioxidant selected from the group consisting of ascorbyl palmitate, tocopherols, and ascorbic acid in the presence of lecithin.  
     
     
         5 . The method of  claim 1 , wherein the composition further comprises an additive selected from the group consisting of aggregants, disaggregants, osmotic pressure regulating salts, buffers, sweeteners, and coloring agents.  
     
     
         6 . The method of  claim 1 , wherein the composition is administered as a formulation selected from the group consisting of tablets, dragees, capsules, granules, solution, suspensions, and lyophilized compositions.  
     
     
         7 . A method of correcting the inhibition of endogenous 13-HODE synthesis by omega-3 fatty acids by incorporating 13-HODE into formulations of omega-3 fatty acids.  
     
     
         8 . The method of  claim 1 , wherein 13-HODE is administered as a pharmaceutical composition comprising 13-HODE and omega-3 fatty acids.  
     
     
         9 . The method of  claim 10  or  11 , wherein the omega-3 fatty acid is selected from the group consisting of EPA, DHA, a derivative of EPA and a derivative of DHA.  
     
     
         10 . The method of  claim 10  or  11 , wherein the omega-3 fatty acid is selected from the group consisting of ethyl-EPA and ethyl-DHA.  
     
     
         11 . A pharmaceutical composition for the oral administration of 13-HODE in which the 13-HODE is formulated with a carrier comprising either a mono-, di-, or triglyceride oil or an ester of a fatty acid containing 16-26 carbon atoms and one or more double bonds.  
     
     
         12 . The pharmaceutical composition of  claim 11  wherein the daily dose of 13-HODE is less than 100 mg.  
     
     
         13 . The pharmaceutical composition of  claim 11  or  12  wherein the carrier is selected from the group consisting of corn, sunflower safflower, cottonseed, grape seed, olive, evening primrose, borage, fish body, and fish liver oils.  
     
     
         14 . The pharmaceutical composition of  claim 11  or  12  wherein the carrier is selected from the group of ethyl esters of the following fatty acids: eicosapentaenoic, oleic, linoleic, alpha-linolenic, stearidonic, gamma-linolenic, dihomogammalinolenic, arachidonic, docosapentaenoic and docosahexaenoic.  
     
     
         15 . The pharmaceutical composition of  claim 11  or  12 , wherein the composition is administered in the form selected from the group consisting of tablets, dragees, capsules, granules, solutions, suspensions and lyophilized compositions.  
     
     
         16 . The pharmaceutical composition of  claim 11  or  12  wherein the composition further comprises a fat-soluble antioxidant selected from the group consisting of ascorbyl palmitate, tocopherols, and ascorbic acid in the presence of lecithin.  
     
     
         17 . The pharmaceutical composition of  claim 11  or  12  wherein the composition further comprises an additive selected from the group consisting of aggregants, disaggregants, osmotic pressure regulating salts, buffers, sweeteners, and coloring agents.  
     
     
         18 . A pharmaceutical composition of 13-HODE comprising 13-HODE and omega-3 fatty acids.  
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the omega-3 fatty acid is selected from the group consisting of EPA, DHA, a derivative of EPA and a derivative of DHA.  
     
     
         20 . The pharmaceutical composition of  claim 18 , wherein the omega-3 fatty acid is selected from the group consisting of ethyl-EPA and ethyl-DHA.  
     
     
         21 . The use of the pharmaceutical composition of  claim 11 ,  12 ,  13 ,  14 ,  15 ,  16 ,  17 ,  18 ,  19 ,  20  and  21  to treat: 
 (a) cardiovascular or cerebrovascular disease  
 (b) inflammatory or autoimmune disease  
 (c) infection with bacteria, viruses, fungi, or protozoa,  
 (d) respiratory disease  
 (e) gastrointestinal disease  
 (f) renal or urinary tract disease  
 (g) skin disease  
 (h) neurological or psychiatric disease  
 (i) disease of the reproductive system  
 (j) diabetes, syndrome A or any complication of diabetes  
 
     
     
         22 . The use of the pharmaceutical compositions of  11 ,  12 ,  13 ,  14 ,  15 ,  16 ,  17 ,  18 ,  19 ,  20  and  21  to treat a disease or condition associated with overactive protein kinases.  
     
     
         23 . The use of  claim 22  wherein the disease or condition is associated with increase in Protein Kinase C activity and/or an increase in Mitogen Activated Protein Kinase activity.  
     
     
         24 . The use of the pharmaceutical composition of  claims 11  to  21  to treat a disease or condition where endothelial function is disordered.  
     
     
         25 . The use of the pharmaceutical composition of  claims 11  to  21  to treat cancer or the metastatic spread of cancer.  
     
     
         26 . The use of the pharmaceutical composition of  claims 11  to  21  to prevent cancer or the metastatic spread of cancer.