Cholesterol absorption inhibitor and omega 3 fatty acids for the reduction of cholesterol and for the prevention or reduction of cardiovascular, cardiac and vascular events

Abstract

A composition and a method of treatment for the reduction of risk factors for cardiovascular disease utilizing a combination of lipid lowering cholesterol absorption inhibitors, e.g. azetidinones, with mixtures of an omega-3 fatty acid formulation containing about 90% or more omega 3 fatty acids by weight including a combination of Eicosapentaenoic acid (EPA), Docosapentaenoic acid (DPA) and Docosahexaenoic acid (DHA) in a weight ratio of EPA:DHA of from 5.7 to 6.3, wherein the sum of the EPA, DHA and DPA represent about 82% by weight of the total formulation and about 92% of the total omega 3 fatty acid content of the composition are taught.

What is claimed is: 
     
         1 . A pharmaceutical formulation for treatment or prophylaxis of risk factors for cardiovascular disease (CVD), protection against sudden death in patients with cardiovascular disease, reduction of overall serum cholesterol levels, reductions in high blood pressure, increase in the HDL:LDL ratio, and reduction of triglycerides comprising:
 a mixture containing omega-3 fatty acids including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) wherein the weight ratio of EPA:DHA is in the range of 5.7:1-6.3:1, the formulation contains about 90% or more by weight omega-3 fatty acids, and the EPA, DHA and DPA comprise about 82% by weight of the content of the formulation; and   at least one azetidinone cholesterol absorption inhibitor or pharmaceutically acceptable salt thereof or a combination thereof.   
     
     
         2 . The formulation in accordance with  claim 1 , comprising about 25 mg/g of DPA. 
     
     
         3 . The formulation in accordance with  claim 1 , further comprising about 30 mg/g of arachidonic acid (AA). 
     
     
         4 . The formulation in accordance with  claim 1 , further comprising about 30 mg/g of one or more omega-3 fatty acids having 18 carbon atoms. 
     
     
         5 . The formulation in accordance with  claim 4 , wherein said one or more 18 carbon atom omega-3 fatty acid is selected from the group consisting of alpha-linolenic acid (ALA), stearidonic acid (SDA) and combinations thereof. 
     
     
         6 . The formulation in accordance with  claim 1 , wherein the omega-3 fatty acids are in the form of ethyl esters and pharmaceutically acceptable salts thereof. 
     
     
         7 . The formulation in accordance with  claim 1 , wherein the omega-3 fatty acids are in the form of triglycerides and pharmaceutically acceptable salts thereof. 
     
     
         8 . The formulation in accordance with  claim 1 , wherein the omega-3 fatty acids are in the form of phospholipids and pharmaceutically acceptable salts thereof. 
     
     
         9 . The formulation in accordance with  claim 1 , in a unit dosage form comprising from about 645 to about 715 mg/gm EPA from about 105 to about 115 mg/gm, DHA and from about 22 to about 28 mg/gm, DPA. 
     
     
         10 . The formulation in accordance with  claim 1 , in a unit dosage form comprising at least 680 mg EPA, at least 110 mg DHA and at least 25 mg DPA. 
     
     
         11 . The formulation in accordance with  claim 9 , wherein the unit dosage form further includes about 30 mg of AA. 
     
     
         12 . The formulation in accordance with  claim 9 , wherein the unit dosage form further includes about 30 mg/g of omega-3 fatty acids having 18 carbon atoms. 
     
     
         13 . The formulation in accordance with  claim 12 , wherein said one or more 18 carbon atom omega-3 fatty acid is selected from the group consisting of alpha-linolenic acid (ALA), stearidonic acid (SDA) and combinations thereof 
     
     
         14 . The formulation in accordance with  claim 9 , wherein the formulation additionally comprises a stabilizer. 
     
     
         15 . The formulation in accordance with  claim 14 , wherein the stabilizer is tocopherol in an amount of about 0.2%. 
     
     
         16 . The formulation in accordance with  claim 9 , wherein the unit dosage form may comprise tablets, capsules, pills, powders, granules, and oral solutions or suspensions. 
     
     
         17 . The formulation in accordance with  claim 16 , wherein the unit dosage form is a gel or liquid capsule. 
     
     
         18 . A pharmaceutical formulation for treatment or prophylaxis of risk factors for cardiovascular disease (CVD), protection against sudden death in patients with cardiovascular disease, reduction of overall serum cholesterol levels, reductions in high blood pressure, increase in the HDL:LDL ratio, and reduction of triglycerides comprising:
 a mixture containing omega-3 fatty acids including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) wherein the weight ratio of EPA:DHA is in the range of 5.7:1-6.3:1; the formulation contains about 90% or more by weight omega-3 fatty acids, and the EPA, DHA and DPA comprise about 82% by weight of the content of the formulation; said formulation contains about 25 mg/g of DPA, about 30 mg/g of arachidonic acid (AA), and about 30 mg/g of one or more omega-3 fatty acids having 18 carbon atoms, wherein said 18 carbon atom omega-3 fatty acid is selected from the group consisting of alpha-linolenic acid (ALA), stearidonic acid (SDA) and combinations thereof; and   at least one azetidinone cholesterol absorption inhibitor or pharmaceutically acceptable salt thereof or a combination thereof.   
     
     
         19 . A pharmaceutical formulation for treatment or prophylaxis of risk factors for cardiovascular disease (CVD), protection against sudden death in patients with cardiovascular disease, reduction of overall serum cholesterol levels, reductions in high blood pressure, increase in the HDL:LDL ratio, and reduction of triglycerides comprising:
 a mixture containing omega-3 fatty acids including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) wherein the weight ratio of EPA:DHA is in the range of 5.7:1-6.3:1, the amount of EPA+DHA in the formulation is about 82.62% to about 87.82% by weight of the total fatty acid content of the formulation, and about 88.26% to about 93.06% by weight of the total omega-3 content of the formulation; the formulation contains from about 93.15% to about 94.87% by weight omega-3 fatty acids; the sum of EPA, DHA and DPA are from about 85.72% to about 87.82% by weight of the total fatty acids in the formulation, and from about 91.38% to about 95.94% by weight of the total omega-3 present in the formulation; said formulation contains about 2.53% to about 3.13% by weight of the total fatty acids in the formulation of DPA, about 3.04% to about 3.48% by weight of the total fatty acids in the formulation of arachidonic acid (AA), and about 3.21% to about 3.45% by weight of the total fatty acids in the formulation, of omega-3 fatty acids having 18 carbon atoms, wherein said 18 carbon atom omega-3 fatty acids are alpha-linolenic acid (ALA) and stearidonic acid (SDA); and wherein the sum of ALA and SDA is about 3.40% to about 3.68% by weight of the total omega-3 present in the formulation; and   at least one azetidinone cholesterol absorption inhibitor or pharmaceutically acceptable salt thereof or a combination thereof.   
     
     
         20 . A process for the treatment of, or prophylaxis of risk factors for, cardiovascular disease (CVD), protection against sudden death in patients with cardiovascular disease, reduction of overall serum cholesterol levels, reductions in high blood pressure, increase in the HDL:LDL ratio, and reduction of triglycerides and homocysteine levels comprising:
 identifying a patient population that exhibits deficiencies in omega-3 fatty acids, and administering to said patient population a formulation in accordance with  claim 1 ;   whereby a therapeutic effect is achieved.   
     
     
         21 . A process for the treatment of, or prophylaxis of risk factors for, cardiovascular disease (CVD), protection against sudden death in patients with cardiovascular disease, reduction of overall serum cholesterol levels, reductions in high blood pressure, increase in the HDL:LDL ratio, and reduction of triglycerides and homocysteine levels comprising:
 identifying a patient population that exhibits deficiencies in omega-3 fatty acids, and administering to said patient population a formulation in accordance with  claim 18 ;   whereby a therapeutic effect is achieved.   
     
     
         22 . A process for the treatment of, or prophylaxis of risk factors for, cardiovascular disease (CVD), protection against sudden death in patients with cardiovascular disease, reduction of overall serum cholesterol levels, reductions in high blood pressure, increase in the HDL:LDL ratio, and reduction of triglycerides and homocysteine levels comprising:
 identifying a patient population that exhibits deficiencies in omega-3 fatty acids, and administering to said patient population a formulation in accordance with  claim 19 ;   whereby a therapeutic effect is achieved.   
     
     
         23 . A process in accordance with  claim 1 , for achieving an indomethacin-independent sustained vasodilatory effect comprising:
 identifying a patient population that exhibits deficiencies in omega-3 fatty acids; and   administering to said patient population a formulation in accordance with  claim 1 ;   whereby a therapeutic effect is achieved.   
     
     
         24 . A process in accordance with  claim 18 , for achieving an indomethacin-independent sustained vasodilatory effect comprising:
 identifying a patient population that exhibits deficiencies in omega-3 fatty acids; and   administering to said patient population a formulation in accordance with  claim 18 ;   whereby a therapeutic effect is achieved.   
     
     
         25 . A process in accordance with  claim 19 , for achieving an indomethacin-independent sustained vasodilatory effect comprising:
 identifying a patient population that exhibits deficiencies in omega-3 fatty acids; and   administering to said patient population a formulation in accordance with  claim 19 ;   whereby a therapeutic effect is achieved.