Compositions containing omega-3 oil and uses thereof

Abstract

The invention provides pharmaceutical compositions containing omega-3 oil and a non-hydrophilic co-solvent that have an increased absorption rate. The pharmaceutical compositions may further contain one or more pharmaceutical organic molecules. The invention further provides kits containing these pharmaceutical compositions, methods for formulating pharmaceutical compositions containing omega-3 oil, and methods for decreasing the likelihood of developing cardiovascular disease, decreasing triglyceride or LDL cholesterol levels, decreasing pain or inflammation, treating diabetes, chronic pulmonary diseases, or irritable bowel syndrome, decreasing symptoms of an autoimmune disease or allergic conditions.

What is claimed is: 
     
         1 . A composition comprising omega-3 oil in a non-hydrophilic co-solvent comprising a herbal-based oil, vitamin E, medium chain triglycerides (MCTs), lecithin, and phosphatidylcholine. 
     
     
         2 . The composition of  claim 1 , wherein said composition is formulated as a liquid. 
     
     
         3 . The composition of  claim 1 , wherein the omega-3 oil is from a natural source. 
     
     
         4 . The composition of  claim 3 , wherein the natural source is selected from the group consisting of: salmon, herring, mackerel, and sardines. 
     
     
         5 . The composition of  claim 1 , wherein the omega-3 oil is high grade. 
     
     
         6 . The composition of  claim 5 , wherein the high grade omega-3 oil is OmegaMaine omega-3 oils. 
     
     
         7 . The composition of  claim 1 , wherein the omega-3 oil is an alkyl ester of a fatty acid. 
     
     
         8 . The composition of  claim 1 , wherein the omega-3 oil is an alkyl ester of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or a mixture of EPA and DHA. 
     
     
         9 . The composition of  claim 1 , wherein the omega-3 oils are in the form of triglycerides. 
     
     
         10 . The composition of  claim 1 , wherein the omega-3 oils are a mixture of triglycerides and free fatty acids. 
     
     
         11 . The composition of  claim 2 , wherein said compositions is formulated in a dose containing greater than 3.0 g combined eicosapentaenoic acid and docosahexanoic acid per 10 mL. 
     
     
         12 . The composition of  claim 11 , wherein said composition is formulated in a dose containing greater than 3.0 g combined EPA and DHA per 10 mL. 
     
     
         13 . The composition of  claim 1 , wherein said non-hydrophilic co-solvent is less than 30% of the composition's total mass. 
     
     
         14 . The composition of  claim 1 , wherein said herbal-based oil is 1% to 10% of the composition's total mass. 
     
     
         15 . The composition of  claim 14 , wherein said herbal-based oil is 3% to 5% of the composition's total mass. 
     
     
         16 . The composition of  claim 1 , wherein the herbal-based oil is selected from the group consisting of rosemary oil, basil oil, turmeric oil, and ginger oil. 
     
     
         17 . The composition of  claim 14 , wherein said herbal-based oil is rosemary oil. 
     
     
         18 . The composition of  claim 1 , wherein the amount of vitamin E present in a single dose of said composition is between 13.4 to 134 mg. 
     
     
         19 . The composition of  claim 1 , wherein the amount of vitamin E present is 1.3% to 13.4% of the composition's mass. 
     
     
         20 . The composition of  claim 1 , wherein said MCTs are from coconut oil. 
     
     
         21 . The composition of  claim 1 , wherein said MCTs are between 1% to 10% of the composition's total mass. 
     
     
         22 . The composition of  claim 21 , wherein said MCTs are 5% of the composition's total mass. 
     
     
         23 . The composition of  claim 1 , wherein phosphatidylcholine is 0.5% to 10% of the composition's total mass. 
     
     
         24 . The composition of  claim 23 , wherein said phosphatidylcholine is 2% to 6% of the composition's total mass. 
     
     
         25 . The composition of  claim 1 , further comprising one or more nitric oxide-stimulating or -releasing agent(s). 
     
     
         26 . The composition of  claim 25 , wherein said nitric oxide-stimulating or -releasing agent is selected from the group of arginine, a di-arginine, and citrulline. 
     
     
         27 . The composition of  claim 1 , further comprising glucosamine. 
     
     
         28 . The composition of  claim 27 , wherein said herbal-based oil is rosemary oil. 
     
     
         29 . The composition of  claim 1 , wherein said composition further comprises ethanol. 
     
     
         30 . The composition of  claim 1 , wherein said composition further comprises a Tween surfactant. 
     
     
         31 . The composition of  claim 30 , wherein said Tween surfactant is selected from the group consisting of: Tween-80, Tween-60, Tween-40, and Tween-20. 
     
     
         32 . The composition of  claim 31 , wherein said Tween surfactant is Tween-80. 
     
     
         33 . The composition of  claim 30 , further comprising ethanol. 
     
     
         34 . The composition of  claim 1 , further comprising one or more therapeutic organic molecule(s) with a molecular weight between 100 g/mole and 800 g/mole, a log P value greater than 2, or a melting point below 200° C. 
     
     
         35 . The composition of  claim 33 , further comprising one or more therapeutic organic molecule(s) with a molecular weight between 100 g/mole and 800 g/mole, a log P value greater than 2, or a melting point below 200° C. 
     
     
         36 . The composition of  claim 35 , wherein said therapeutic organic molecule is a non-steroidal anti-inflammatory drug (NSAID) or a disease-modifying anti-rheumatic drug (DMARD). 
     
     
         37 . The composition of  claim 35 , wherein said therapeutic organic molecule is fenofibrate, a statin, or niacin. 
     
     
         38 . The composition of  claim 37 , wherein a dose of said composition contains 5 mg/mL to 20 mg/mL fenofibrate. 
     
     
         39 . The composition of  claim 38 , wherein said dose contains 10 mg/mL to 15 mg/mL fenofibrate. 
     
     
         40 . The composition of  claim 37 , wherein a dose of said composition contains 1 mg/mL to 4 mg/mL of a statin. 
     
     
         41 . The composition of  claim 40 , wherein a dose of said composition contains 0.5 mg/mL to 2 mg/mL of a statin. 
     
     
         42 . The composition of  claim 36 , wherein said NSAID is selected from the group consisting of ketoprofen, ibuprofen, diflunisal, diclofenac, and naproxen. 
     
     
         43 . The composition of  claim 42 , wherein said NSAID is ketoprofen. 
     
     
         44 . The composition of  claim 36 , wherein said DMARD is methotrexate. 
     
     
         45 . The composition of  claim 36 , wherein said herbal-based oil is rosemary oil and said composition further comprises glucosamine. 
     
     
         46 . The composition of  claim 35 , wherein said therapeutic organic molecule is an H-1 antihistamine. 
     
     
         47 . The composition of  claim 46 , wherein the H-1 antihistamine is from the tricyclic class of antihistamines. 
     
     
         48 . The composition of  claim 47 , wherein the tricyclic antihistamine is imipramine or doxepin. 
     
     
         49 . The composition of  claim 46 , wherein the H-1 antihistamine is from the non-tricyclic class of antihistamines. 
     
     
         50 . The composition of  claim 49 , wherein the non-tricyclic antihistamine is diphenhydramine or triporlidine. 
     
     
         51 . The composition of  claim 1 , further comprising one or more agents selected from the group consisting of: phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid. 
     
     
         52 . The composition of  claim 51  comprising phosphatidylinositol and phosphatidic acid. 
     
     
         53 . The composition of  claim 1 , wherein 10% of the omega-3 oil is in solution and the remaining 90% of the omega-3 oil is in stable suspension form. 
     
     
         54 . The composition of  claim 2 , wherein said composition is formulated for oral administration. 
     
     
         55 . A composition comprising: 70% to 80% w/w of natural fish oil as a source of omega-3 oil; 5% to 15% w/w of coconut oil as a source of medium chain triglycerides; 0.5% to 5% w/w polytocopherol as a source of vitamin E; 1% to 10% w/w absolute ethanol; 1% to 10% w/w sorbital laurate; and 1% to 10% w/w cremaphor. 
     
     
         56 . A composition comprising: 70% to 80% w/w of natural fish oil as a source of omega-3 oil: 5% to 15% w/w coconut oil as a source of medium chain triglycerides; 0.5% to 5% w/w polytocopherol as a source of vitamin E; 1% to 5% w/w absolute ethanol; and 5% to 15% cremaphor. 
     
     
         57 . A composition comprising: 65% to 75% w/w of natural fish oil as a source of omega-3 oil; 1% to 10% w/w of coconut oil as a source of medium chain triglycerides; 0.5% to 5% w/w polytocopherol as a source of vitamin E; 1% to 10% w/w absolute ethanol; 1% to 10% w/w sorbital laurate; 1% to 10% w/w cremaphor; and 1% to 10% w/w of a therapeutic organic molecule. 
     
     
         58 . A composition comprising: 65% to 75% w/w of natural fish oil as a source of omega-3 oil; 1% to 10% w/w of coconut oil as a source of medium chain triglycerides; 0.5% to 5% w/w polytocopherol as a source of vitamin E; 1% to 5% w/w absolute ethanol; 1% to 10% w/w sorbital laurate; 1% to 15% w/w cremaphor; and 1% to 10% w/w of a therapeutic organic molecule. 
     
     
         59 . A kit comprising:
 (i) the composition of  claim 1 ; and   (ii) instructions for administering said composition to a subject.   
     
     
         60 . The kit of  claim 59 , wherein said composition is formulated as a liquid. 
     
     
         61 . The kit of  claim 60 , wherein said composition is formulated for oral administration. 
     
     
         62 . The kit of  claim 59 , wherein said composition further comprises one or more therapeutic organic molecule(s) with a molecule weight between 100 g/mole and 800 g/mole, a log P value of greater than 2, or a melting point below 200° C. 
     
     
         63 . The kit of  claim 62 , wherein the therapeutic organic molecule is a non-steroidal anti-inflammatory drug (NSAID) or a disease-modifying anti-rheumatic drug (DMARD). 
     
     
         64 . The kit of  claim 62 , wherein the therapeutic organic molecule is an H-1 antihistamine. 
     
     
         65 . The kit of  claim 64 , wherein the H-1 antihistamine is from the tricyclic class of antihistamines. 
     
     
         66 . The kit of  claim 65 , wherein the tricyclic antihistamine is imipramine or doxepin. 
     
     
         67 . The kit of  claim 64 , wherein the H-1 antihistamine is from the non-tricyclic class of antihistamines. 
     
     
         68 . The kit of  claim 67 , wherein the non-tricyclic antihistamine is diphenhydramine or triprolidine. 
     
     
         69 . The kit of  claim 62 , wherein the therapeutic organic molecule is fenofibrate, a statin, or niacin. 
     
     
         70 . The kit of  claim 62 , wherein said herbal-based oil is rosemary oil and said composition further comprises glucosamine. 
     
     
         71 . The kit of  claim 63 , wherein said herbal-based oil is rosemary oil and said composition further comprises glucosamine. 
     
     
         72 . The kit of  claim 59 , wherein said composition further comprises phosphatidylinositol and phosphatidic acid. 
     
     
         73 . The kit of  claim 59 , wherein said composition is formulated for oral administration. 
     
     
         74 . The kit of  claim 59 , further comprising at least one additional composition containing a NSAID or a DMARD. 
     
     
         75 . The kit of  claim 59 , further comprising at least one additional composition containing an H-1 antihistamine. 
     
     
         76 . The kit of  claim 75 , wherein said H-1 antihistamine is from the tricyclic class of antihistamines. 
     
     
         77 . The kit of  claim 76 , wherein the tricyclic antihistamine is imipramine or doxepin. 
     
     
         78 . The kit of  claim 75 , wherein said H-1 antihistamine is from the non-tricyclic class of antihistamines. 
     
     
         79 . The kit of  claim 78 , wherein said non-tricyclic antihistamine is diphenhydramine or triprolidine. 
     
     
         80 . A method of decreasing the likelihood of developing a cardiovascular disease by administering to a subject the composition of  claim 1  for a time and in an amount sufficient to reduce triglyceride or low-density lipoprotein (LDL) cholesterol levels in the blood of said subject, or to increase the amount of omega-3 oil present in the cell membranes of red blood cells in said subject. 
     
     
         81 . The method of  claim 80 , wherein said composition is administered once a day. 
     
     
         82 . The method of  claim 81 , wherein said composition is administered orally. 
     
     
         83 . The method of  claim 82 , wherein said composition is administered as a liquid. 
     
     
         84 . The method of  claim 80 , wherein said composition is formulated as a liquid. 
     
     
         85 . The method of  claim 84 , wherein said composition is administered in a dose containing greater than 3.0 g combined eicosatrienoic acid and docosahexaenoic acid in 10 mL. 
     
     
         86 . The method of  claim 80 , wherein said administering results in at least a 10% decrease in triglyceride or LDL cholesterol levels in the blood of said subject, or at least a 10% increase in the amount of omega-3 oil present in the cell membranes of red blood cells in said subject. 
     
     
         87 . The method of  claim 80 , wherein said administering results in at least a 5% decrease in blood pressure. 
     
     
         88 . The method of  claim 80 , wherein said administering results in a reduction in nausea or esophageal reflux compared to the nausea and esophageal reflux observed following administration of omega-3 oils alone. 
     
     
         89 . A method of decreasing the triglyceride or low-density lipoprotein (LDL) cholesterol levels in a subject comprising administering the composition of  claim 1  to said subject. 
     
     
         90 . The method of  claim 89 , wherein said composition is administered to said subject once a day. 
     
     
         91 . The method of  claim 90 , wherein said composition is administered orally. 
     
     
         92 . The method of  claim 91 , wherein said composition is formulated as a liquid. 
     
     
         93 . The method of  claim 89 , wherein said composition is formulated as a liquid. 
     
     
         94 . The method of  claim 93 , wherein said composition is administered in a dose containing greater than 3.0 g combined eicosapentaenoic acid and docosahexaenoic acid in 10 mL. 
     
     
         95 . The method of  claim 89 , wherein said administering results in at least a 10% decrease in triglyceride or LDL cholesterol levels in the blood of said subject, or at least a 10% increase in omega-3 oil present in the cell membranes of red blood cells in said subject. 
     
     
         96 . The method of  claim 89 , wherein said administering results in a reduction in nausea or esophageal reflux compared to the nausea and esophageal reflux observed following administration of omega-3 oils alone. 
     
     
         97 . A method of treating diabetes comprising administering a composition of  claim 1  for a time and in an amount sufficient to increase insulin sensitivity in said subject or increase high-density lipoprotein (HDL) cholesterol levels in the blood of said subject. 
     
     
         98 . The method of  claim 97 , wherein said composition further comprises phosphitidylinositol, phosphatidic acid, phosphatidylethanolamine, and/or phosphatidylserine. 
     
     
         99 . The method of  claim 98 , wherein said composition comprises phosphitidylinositol and phosphatidic acid. 
     
     
         100 . The method of  claim 97 , wherein said composition is administered to said subject once a day. 
     
     
         101 . The method of  claim 100 , wherein said composition is administered orally. 
     
     
         102 . The method of  claim 101 , wherein said compositions is formulated as a liquid. 
     
     
         103 . The method of  claim 97 , wherein said composition is formulated as a liquid. 
     
     
         104 . The method of  claim 103 , wherein said composition is administered in a dose containing greater than 3.0 g combined eicosapentaenoic acid and docosahexaenoic acid in 10 mL. 
     
     
         105 . The method of  claim 97 , wherein said administration results in at least a 10% increase in insulin sensitivity in said subject or at least a 10% increase in HDL cholesterol levels in the blood of said subject. 
     
     
         106 . A method of decreasing pain or inflammation in a subject comprising administering the composition of  claim 1 . 
     
     
         107 . The method of  claim 106 , wherein said composition further comprises a non-steroidal anti-inflammatory drug (NSAID) or a disease-modifying anti-rheumatic drug (DMARD). 
     
     
         108 . The method of  claim 107 , wherein said composition comprises an NSAID and a DMARD. 
     
     
         109 . The method of  claim 106 , wherein said herbal-based oil is rosemary oil and said composition further comprises glucosamine. 
     
     
         110 . The method of  claim 107 , wherein said herbal-based oil is rosemary oil and said composition further comprises glucosamine. 
     
     
         111 . The method of  claim 106 , wherein the composition is administered to said subject once a day. 
     
     
         112 . The method of  claim 106 , wherein said composition is administered orally. 
     
     
         113 . The method of  claim 112 , wherein said composition is formulated as a liquid. 
     
     
         114 . The method of  claim 106 , wherein said composition is administered at the same time as a NSAID or a DMARD. 
     
     
         115 . The method of  claim 106 , wherein said composition is administered prior to a NSAID or a DMARD. 
     
     
         116 . The method of  claim 106 , wherein said administering results in at least a 5% reduction in pain score, at least a 5% reduction in cyclooxygenase (COX)-1 or COX-2 activity, at least a 5% reduction in white blood cell count, or at least a 5% reduction in C-reactive protein, interleukin-6, or TNF-α levels in said subject. 
     
     
         117 . The method of  claim 106 , wherein said administering results in at least a 2-fold decrease in the time to optimal therapeutic effect. 
     
     
         118 . The method of  claim 106 , wherein said administration results in less gastric lesions than administration of a NSAID or a DMARD alone. 
     
     
         119 . A method of treating a chronic pulmonary disease or irritable bowel syndrome, or reducing one or more symptoms of an autoimmune disease comprising administering to a subject a composition of  claim 1 . 
     
     
         120 . The method of  claim 119 , wherein said chronic pulmonary disease is asthma or chronic obstructive pulmonary disease. 
     
     
         121 . The method of  claim 119 , wherein said autoimmune disease is multiple sclerosis or lupus erythematosus. 
     
     
         122 . The method of  claim 119 , wherein said composition further comprises a non-steroidal anti-inflammatory drug (NSAID) or a disease-modifying anti-rheumatic drug (DMARD). 
     
     
         123 . The method of  claim 122 , wherein said composition comprises an NSAID and a DMARD. 
     
     
         124 . The method of  claim 119 , wherein said herbal-based oil is rosemary oil and said composition further comprises glucosamine. 
     
     
         125 . The method of  claim 122 , wherein said herbal-based oil is rosemary oil and said composition further comprises glucosamine. 
     
     
         126 . The method of  claim 119 , wherein the composition is administered to said subject once a day. 
     
     
         127 . The method of  claim 126 , wherein said composition is administered orally. 
     
     
         128 . The method of  claim 127 , wherein said composition is formulated as a liquid. 
     
     
         129 . The method of  claim 119 , wherein said composition is administered at the same time as an NSAID or a DMARD. 
     
     
         130 . The method of  claim 119 , wherein said composition is administered prior to a NSAID or a DMARD. 
     
     
         131 . The method of  claim 119 , wherein said administering results in at least a 2-fold decrease in the time to optimal therapeutic effect. 
     
     
         132 . The method of  claim 119 , wherein said administration results in less gastric lesions than administration of a NSAID or a DMARD alone. 
     
     
         133 . A method of formulating an omega-3 oil-containing pharmaceutical composition having at least a 10% increase in absorption rate relative to the absorption rate of omega-3 oil alone, comprising the step of combining an omega-3 oil with a co-solvent comprising one or more solvents or agents selected from the group consisting of: a herbal-based oil, vitamin E, medium chain triglycerides, lecithin, phosphatidylcholine, glucosamine, ethanol, a Tween surfactant, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid, natural fish oil, coconut oil, polytocopherol, sorbital laurate, cremaphor, an amide of an intermediate (C-6 to C-12) chain fatty acid, an amide of a long chain (C-12 to C-24 fatty acid), lauric alcohol, and lauric acid. 
     
     
         134 . The method of  claim 133 , wherein the co-solvent comprises a herbal-based oil, vitamin E, medium chain triglycerides (MCTs), lecithin, and phosphatidylcholine. 
     
     
         135 . The method of  claim 133 , wherein the co-solvent comprises natural fish oil, coconut oil, polytocopherol, absolute ethanol, sorbital laurate, and cremaphor. 
     
     
         136 . A method of formulating a pharmaceutical composition containing omega-3 oil and one or more therapeutic organic molecule(s) having at least a 10% increase in absorption rate relative to the absorption rate of omega-3 oil alone or the one or more therapeutic organic molecule(s) alone, comprising the step of combining an omega-3 oil and one or more therapeutic organic molecule(s) with a co-solvent comprising one or more solvents or agents selected from the group consisting of: a herbal-based oil, vitamin E, medium chain triglycerides (MCTs), lecithin, phosphatidylcholine, glucosamine, ethanol, a Tween surfactant, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid, natural fish oil, coconut oil, polytocopherol, sorbital laurate, cremaphor, an amide of an intermediate (C-6 to C-12) chain fatty acid, an amide of a long chain (C-12 to C-24 fatty acid), lauric alcohol, and lauric acid. 
     
     
         137 . The method of  claim 136 , wherein the co-solvent comprises a herbal-based oil, vitamin E, MCTs, lecithin, and phosphatidylcholine. 
     
     
         138 . The method of  claim 137 , wherein the co-solvent comprises natural fish oil, coconut oil, polytocopherol, absolute ethanol, sorbital laurate, and cremaphor. 
     
     
         139 . The method of  claim 136 , wherein the one or more therapeutic organic molecule(s) are first combined with the co-solvent to solubilize the one or more therapeutic organic molecule(s), and then the omega-3 oil is added to form the pharmaceutical composition. 
     
     
         140 . The method of  claim 136 , wherein the composition comprises ethanol. 
     
     
         141 . The method of  claim 139 , wherein the composition comprises ethanol, a Tween surfactant, MCTs, vitamin E, and lecithin. 
     
     
         142 . The method of  claim 141 , wherein the Tween surfactant is Tween-80.