Compositions comprising 15-hepe and methods of treating or preventing hematologic disorders, and/or related diseases

Abstract

The present disclosure relates to methods of treating or preventing hematologic disorders by administration of 15-HEPE or compositions thereof.

We claim: 
     
         1 . A method of treating and/or preventing a hematologic disorder in a subject in need thereof, the method comprising administering to the subject 15-hydroxyeicosapentaenoic acid (15-HEPE) or a composition comprising 15-HEPE. 
     
     
         2 . A method of treating and/or preventing a hemoglobin disorder in a subject in need thereof, the method comprising administering to the subject 15-HEPE ora composition comprising 15-HEPE. 
     
     
         3 . A method of treating and/or preventing a red blood cell disorder in a subject in need thereof, the method comprising administering to the subject 15-HEPE ora composition comprising 15-HEPE. 
     
     
         4 . A method of treating and/or preventing hemolytic anemia in a subject in need thereof, the method comprising administering to the subject up to about 8 g of a composition comprising 15-HEPE. 
     
     
         5 . The method of  claim 1 , wherein the hematologic disorder is selected from the group consisting of anemia, blood cancer, and a coagulation defect. 
     
     
         6 . The method of  claim 5 , wherein the anemia is a nutritional anemia, a non-nutritional anemia, or a combination thereof. 
     
     
         7 . The method of  claim 5 , wherein the blood cancer is selected from the group consisting of lymphoma, leukemia, and myeloma. 
     
     
         8 . The method of  claim 5 , wherein the coagulation defect is selected from the group consisting of thrombophilia, hemophilia, Von Willebrand disease, and thrombocytopenia. 
     
     
         9 . The method of any one of the preceding claims, wherein the subject has an increase in red blood cell count, a decrease in red blood cell distribution width, and/or a decrease in reticulocyte count compared to a control subject not receiving the 15-HEPE or the composition. 
     
     
         10 . The method of any one of the preceding claims, wherein the subject has an increase in red blood cell count of at least 10%, at least 15%, at least 20%, at least 25%, or at least 30% compared to a control subject not receiving the 15-HEPE or the composition. 
     
     
         11 . The method of any one of the preceding claims, wherein the subject has a decrease in red blood cell distribution width of from about 15% to about 20%, from about 20% to about 25%, from about 25% to about 30%, from about 30% to about 35%, or from about 35% to about 40% compared to a control subject not receiving the 15-HEPE or the composition. 
     
     
         12 . The method of any one of  claims 9  to  11 , wherein the control subject has a red blood cell distribution width greater than 15%. 
     
     
         13 . The method of any one of the preceding claims, wherein the subject has a decrease in reticulocyte count of at least about 5%, at least about 10%, at least about 15%, or at least about 20% compared to a control subject not receiving the 15-HEPE or the composition. 
     
     
         14 . The method of any one of  claims 9  to  13 , where the control subject has a reticulocyte count greater than 5% of the total number of red blood cells. 
     
     
         15 . The method of any one of  claims 2  to  14 , wherein the hemoglobin disorder and/or the red blood cell disorder is selected from the group consisting of inherited hemolytic anemia, acquired hemolytic anemia, Fanconi anemia, iron deficiency anemia, folate deficiency, B12 deficiency, and myelodysplastic syndrome. 
     
     
         16 . The method of  claim 15 , wherein the inherited hemolytic anemia is selected from the group consisting of sickle cell disease, sickle cell anemia, β-thalassemia, and hereditary spherocytosis. 
     
     
         17 . The method of  claim 15 , wherein the acquired hemolytic anemia is acquired from a disorder or condition selected from the group consisting of a condition secondary to a primary infection, a medication, a hematological malignancy, an autoimmune disease, hypersplenism, positioning of a mechanical heart valve, and a blood transfusion. 
     
     
         18 . The method of  claim 16 , wherein the sickle cell disease and sickle cell anemia are associated with sickle cell crisis, a vaso-occlusive crisis, and/or splenic sequestration. 
     
     
         19 . A method of treating and/or preventing a thrombophilia disorder in a subject in need thereof, the method comprising administering to the subject 15-HEPE ora composition comprising 15-HEPE. 
     
     
         20 . A method of treating and/or preventing thrombophilia in a subject in need thereof, the method comprising administering to the subject 15-HEPE or up to about 8 g of a composition comprising 15-HEPE. 
     
     
         21 . A method of treating and/or preventing a venous thromboembolism in a subject in need thereof, the method comprising administering to the subject 15-HEPE or up to about 8 g of a composition comprising 15-HEPE. 
     
     
         22 . A method of treating and/or preventing an arterial thrombosis in a subject in need thereof, the method comprising administering to the subject 15-HEPE or up to about 8 g of a composition comprising 15-HEPE. 
     
     
         23 . A method of preventing an embolism in a subject in need thereof, the method comprising administering to the subject 15-HEPE or up to about 8 g of a composition comprising 15-HEPE. 
     
     
         24 . The method of any one  claims 19  to  23 , wherein the subject has an increase in prothrombin time, an increase in activated partial thromboplastin time, and/or a decrease in fibrinogen concentration compared to a control subject not receiving the composition. 
     
     
         25 . The method as in any one of the preceding claims, wherein the 15-HEPE is in free acid form, esterified form, conjugate form, or salt form. 
     
     
         26 . The method of any one of the preceding claims, wherein the 15-HEPE represents at least about 90% by weight, of all fatty acids in the composition. 
     
     
         27 . The method of any one of the preceding claims, wherein the composition comprises up to about 2 g of 15-HEPE. 
     
     
         28 . The method of any one of the preceding claims, wherein the composition is administered in 1 to 8 capsules per day. 
     
     
         29 . The method of any one of the preceding claims, wherein the composition comprises at least 2 g of 15-HEPE. 
     
     
         30 . The method of any one of the preceding claims, wherein the composition is formulated to provide about 5 mg of 15-HEPE per kg of bodyweight (mg/kg), about 50 mg/kg, about 250 mg/kg, or about 500 mg/kg to the subject. 
     
     
         31 . The method of any one of the preceding claims, wherein the 15-HEPE or the composition comprising 15-HEPE is orally administered. 
     
     
         32 . The method of any one of the preceding claims, wherein the 15-HEPE is in free acid form, esterified form, conjugate form, or salt form. 
     
     
         33 . The method as in any one of the preceding claims, wherein the esterified form of 15-HEPE is a methyl ester, an ethyl ester, or a combination thereof.