JP2016518315A - ω3 pentaenoic acid composition and method of use - Google Patents

Abstract

An orally administrable composition comprising a fatty acid is provided, the fatty acid comprising an ω3 fatty acid, salt or derivative thereof. The composition can be used for the treatment or prevention of dyslipidemia, cardiovascular, CNS, inflammatory, and other diseases / conditions, or risk factors thereof. The present invention relates to ω3 fatty acid compositions and treats symptoms associated with coronary heart disease (CHD), vascular disease, arteriosclerotic disease, or related conditions, prevents the symptoms and reduces the occurrence of the symptoms And to improve the symptoms.

Description

RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 61 / 780,948, filed March 13, 2013, the contents of which are incorporated herein by reference.

FIELD OF THE INVENTION The present invention relates to ω3 fatty acid compositions and treats symptoms associated with coronary heart disease (CHD), vascular disease, arteriosclerotic disease, or related conditions, prevents the symptoms, It relates to a method for reducing the incidence and improving the symptoms. The present invention also provides methods for the treatment and / or prevention and / or alleviation of cardiac events and / or cardiovascular events and / or vascular events or symptoms.

BACKGROUND OF THE INVENTION Marine oil, also commonly referred to as fish oil, is the two major omega-3 fatty acids known to control lipid metabolism, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Is an excellent raw material. Omega 3 fatty acids have been shown to have a beneficial effect on risk factors for cardiovascular disease, particularly mild hypertension, hypertriglyceridemia, and on coagulation factor VII phospholipid complex activity. Omega 3 fatty acids reduce serum triglycerides (TG), increase serum HDL cholesterol, reduce systolic and diastolic blood pressure and pulse rate, and reduce the activity of blood coagulation factor VII-phospholipid complexes. Furthermore, ω3 fatty acids are considered well tolerated without causing severe side effects.

The table below lists the most common ω3 fatty acids, including their three letter abbreviations. In this application, unless otherwise indicated, the use of any three letter abbreviation shall refer to ω3 fatty acids (eg DPA or DPA 22: 5 (n-3) or DPA 22: 5-n3 or DPA 22: 5n3 or DPA-n3 both mean the ω3 isomer of docosapentaenoic acid).

  One form of ω3 fatty acid is described in USP35 for a concentrate of ω3 long chain polyunsaturated fatty acids from fish oil containing DHA ethyl ester, EPA ethyl ester, and ethyl ester of other ω3 fatty acids (LOVAZA®) ) And are sold under the trademarks OMACOR (registered trademark) and LOVAZA (registered trademark). Such forms of ω3 fatty acids comprise at least 90% ω3 fatty acids, at least 80% of which are EPA + DHA (1.2: 1 ratio), such as US Pat. Nos. 5,502,077 and 5,656,667. (Patent Document 2) and No. 5,698,594 (Patent Document 3). LOVAZA® (ω3 acid ethyl ester) is required for the treatment of hypertriglyceridemic patients with TG levels of 500 mg / dL or higher.

  Another form of omega-3 fatty acid concentrate is sold under the trademark EPADEL® for the treatment of dyslipidemia. This product is described as 98% EPA ethyl ester in Lancet (Vol.369; March 31, 2007; 1090-1098 (Non-Patent Document 1)) reporting on a large-scale survey of EPADEL®. Yes. EPADEL® is known to contain less than 1% fatty acids other than EPA.

  Similar to EPADEL®, another form of ω3 fatty acid concentrate consists almost entirely of EPA ethyl ester, known as the development stage name AMR101 or the trade name VASCEPA®. This product can be found in US Patent Application No. 2010/0278879, at least 95% EPA (usually referred to as 97% or at least 96% in company releases and references) and any less than 1% It is described as containing other fatty acids. AMR101 was previously under development for the treatment of Huntington's disease, but failed Phase III clinical development. Subsequently, AMR101 was added to the development program for hypertriglyceridemia and mixed dyslipidemia.

  Yet another concentrate of ω3 long chain polyunsaturated fatty acids from fish oil containing about 75% DHA and EPA as free fatty acids is known as the development stage name EPANOVA ™. This product is described as containing approximately 55% EPA and 20% DHA. EPANOVA ™ was previously under development for the treatment of Crohn's disease but failed phase III clinical development. EPANOVA ™ was subsequently added to the development program for hypertriglyceridemia and mixed dyslipidemia.

  In general, the bioavailability and therapeutic effect of an ω3 fatty acid composition is dose dependent, ie, the higher the dose, the higher the therapeutic effect and bioavailability. However, the effect of each particular ω3 fatty acid composition can be different, and therefore the level of therapeutic effect of one composition at a given dose can be compared to that of other ω3 fatty acid compositions at the same or similar doses. It cannot always be inferred from the level of therapeutic effect.

  ω3 fatty acids are known to be “essential fatty acids”. There are two series of essential fatty acids (EFA) in humans. They are called “essential” because they cannot be synthesized de novo in mammals. In humans, these fatty acids can be interconverted within the series, but the ω6 (n-6) series cannot be converted to the ω3 series, and the ω3 (n-3) series must be converted to the ω6 series. I can't. The main EFAs in the diet are the ω6 series of linoleic acid and the ω3 series of α-linolenic acid. However, to perform most of the biological effects of these “parent” EFAs, they must be metabolized to other long chain fatty acids. Perhaps each fatty acid has a specific role in the body. Scientific literature is particularly important in the n-6 series: dihomo gamma linolenic acid (DGLA, 20: 3-n6) and arachidonic acid (ARA, 20: 4-n6), while in the n-3 series It is suggested that eicosapentaenoic acid (EPA, 20: 5-n3) and docosahexaenoic acid (DHA, 22: 6-n3) are particularly important.

  In the invention described in US Pat. No. 6,479,544, it has been found that ARA is highly desirable rather than undesirable, and it may be useful to administer ARA in combination with EPA. Yes. As set forth in the granted claims of this patent, the present invention provides a pharmaceutical formulation containing eicosapentaenoic acid or any suitable derivative (hereinafter collectively referred to as EPA) and arachidonic acid (ARA). provide. ARA may be replaced with one or more of its precursors DGLA or GLA. In this reference, the ratio of EPA to ARA is preferably 1: 1 to 20: 1.

  Patent application PCT / GB 2004/000242 describes the treatment or prevention of psoriasis with a formulation containing more than 95% EPA and less than 2% DHA. In another embodiment of the invention, EPA is replaced with DPA.

  Patent application PCT / NL 2006/050291 (Patent Document 7) (WO / 2007/058538 (Patent Document 8), GB 0301701.9) (Patent Document 9) improves the barrier function by improving the integrity of the intestinal barrier. Describes combinations of indigestible oligosaccharides with long-chain polyunsaturated fatty acids such as ARA, EPA, DA, and combinations thereof to stimulate intestinal maturation and / or reduce intestinal barrier permeability Has been.

  Lindeborg et al. (Prostag Leukotr Ess, 2013, 88: 313-319) discloses a test to assess postprandial metabolism of docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA) in humans. Yes.

  Holub et al. (Lipids, 2011, 46: 399-407) reported that docosapentaenoic acid for the levels of serum lipids and tissue lipid classes in rat liver, heart, and kidney and their fatty acid composition ( A study has been disclosed that evaluates the effects of oral supplementation of DPA).

  Cardiovascular disease includes a number of problems, many of which are associated with a process called atherosclerosis. Atherosclerosis is a condition that occurs when plaque builds up on the walls of an artery. This deposition narrows the artery and makes it difficult for blood to flow. If a thrombus is formed, blood flow may stop. If clotting occurs, it can stop the blood flow. This can cause conditions or events such as myocardial infarction, stroke, heart failure, arrhythmia, valve dysfunction and death.

  All references cited herein are incorporated by reference in their entirety.

U.S. Pat.No. 5,502,077 U.S. Pat.No. 5,656,667 U.S. Pat.No. 5,698,594 US Patent Application No. 2010/0278879 U.S. Patent No. 6,479,544 PCT / GB 2004/000242 PCT / NL 2006/050291 WO / 2007/058538 GB 0301701.9

Lancet, Vol.369; March 31, 2007; 1090-1098 Lindeborg et al., Prostag Leukotr Ess, 2013, 88: 313-319 Holub et al., Lipids, 2011, 46: 399-407

  The present invention provides ω3 fatty acid compositions and methods of administering these compositions.

  The present invention relates to a pharmaceutical composition containing a fatty acid, wherein at least 50% by weight of the fatty acid contains an ω3 fatty acid, a salt, an ester or a derivative thereof, and the ω3 fatty acid is eicosapentaenoic acid (EPA), docosapentaenoic acid. (DPA), and docosahexaenoic acid (DHA), the ratio of DHA to EPA (DHA: EPA) is less than 1:10, and the ratio of DHA to DPA (DHA: DPA) is less than 2: 1. A pharmaceutical composition is provided.

  The present invention relates to a pharmaceutical composition comprising eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) in an amount of about 70% to about 95% of the total amount of fatty acids, wherein 5% of the total amount of fatty acids Pharmaceutical compositions comprising the following docosahexaenoic acid (DHA) and having a DHA: DPA ratio of 1: 1 or less are provided.

  The present invention is a pharmaceutical composition comprising a pharmaceutical composition comprising eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) in an amount of about 750 mg / g to about 950 mg / g comprising: Provided is a pharmaceutical composition comprising no more than 5% DHA of the total amount of fatty acids and having a DHA: DPA ratio of 1: 1 or less.

  The present invention is a pharmaceutical composition comprising eicosapentaenoic acid (EPA) at a daily dose of about 1000 mg to about 5000 mg and further comprising docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), Provided is a pharmaceutical composition comprising no more than 5% DHA of the total amount of fatty acids and having a DHA: DPA ratio of 1: 1 or less.

  The present invention provides a pharmaceutical composition comprising eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA), wherein the amount of EPA and DPA is about 55% by weight or more of the total amount of fatty acids, And a pharmaceutical composition having a DHA: DPA ratio of 1: 1 or less.

  The present invention relates to docosapentaenoic acid (DPA) in an amount of about 50% to about 80% of the total amount of fatty acids, docosahexaenoic acid (DHA) in an amount of about 25% to about 40% of the total amount of fatty acids, and optionally fatty acids A pharmaceutical composition comprising eicosapentaenoic acid (EPA) in an amount of about 10% of the total amount of

  In some embodiments, the composition of the invention comprises heneicosapentaenoic acid (HPA), arachidonic acid (ARA), and ω6-docosapentaenoic acid (n-6 DPA), tetracosapentaenoic acid (TPA), And / or additional fatty acids such as γ-linolenic acid (GLA).

  The present invention provides a method comprising administering a composition. The present invention treats symptoms associated with coronary heart disease (CHD), vascular disease, arteriosclerotic disease, or related conditions, prevents the symptoms, reduces the occurrence of the symptoms, and improves the symptoms A method is provided comprising the step of administering a composition of the invention to a subject in need thereof. The invention also relates to a subject in need thereof, such as a subject susceptible to or suffering from a vascular / cardiovascular disease or condition, a subject at risk of causing a vascular / cardiovascular event, or a vascular / cardiovascular disease or Provided is a method of treating a patient by administering an effective amount of such a composition to a subject in need of treatment of the condition.

DETAILED DESCRIPTION OF THE INVENTION The present invention includes fatty acids, wherein at least 50% by weight of the fatty acids comprise ω3 fatty acids, salts, esters, or derivatives thereof, wherein the ω3 fatty acids are eicosapentaenoic acid (EPA; C20: 5-n3), Contains pentaenoic acid (DPA; C22: 5-n3), and docosahexaenoic acid (DHA; C22: 6-n3), the ratio of DHA to EPA (DHA: EPA) is less than 1:20, and DHA to DPA Provided is an orally administrable composition having a (DHA: DPA) ratio of less than 2: 1.

  The present invention comprises a fatty acid, wherein at least 50% by weight of the fatty acid comprises an ω3 fatty acid, salt, ester, or derivative thereof, wherein the ω3 fatty acid is eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). And a docosahexaenoic acid DHA to EPA (DHA: EPA) ratio of less than 1:10 and a DHA to DPA (DHA: DPA) ratio of less than 2: 1, and A method of using the present composition is provided. In some embodiments, the composition comprises EPA in an amount of about 70% to about 95% of the total amount of fatty acids. In some embodiments, the composition comprises less than about 5% DHA of the total amount of fatty acids. In some embodiments, the composition comprises DPA in an amount of about 5% to about 15% of the total amount of fatty acids. In some embodiments, the ratio of EPA to DPA (EPA: DPA) is less than about 1: 1. In some embodiments, the composition further comprises heneicosapentaenoic acid (HPA) in an amount of at least 1% of the total amount of fatty acids.

  The present invention relates to a pharmaceutical composition comprising eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) in an amount of about 70% to about 95% of the total amount of fatty acids, wherein 5% of the total amount of fatty acids Pharmaceutical compositions comprising the following docosahexaenoic acid (DHA) and having a DHA: DPA ratio of 1: 1 or less are provided, as well as methods of using the composition. In some embodiments, the composition comprises DPA in an amount of about 5% to about 15% of the total amount of fatty acids. In some embodiments, the composition further comprises heneicosapentaenoic acid (HPA) in an amount of at least 1% of the total amount of fatty acids. In some embodiments, the ratio of EPA to DPA (EPA: DPA) is less than about 1: 1. In some embodiments, the ratio of DHA: EPA is less than about 1:10.

  The present invention is a pharmaceutical composition comprising a pharmaceutical composition comprising eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) in an amount of about 750 mg / g to about 950 mg / g comprising: Pharmaceutical compositions comprising 5% or less DHA of the total amount of fatty acids and having a DHA: DPA ratio of 1: 1 or less and methods of using the compositions are provided. In some embodiments, the composition comprises DPA in an amount of about 5% to about 15% of the total amount of fatty acids. In some embodiments, the composition further comprises heneicosapentaenoic acid (HPA) in an amount of at least 1% of the total amount of fatty acids. In some embodiments, the ratio of EPA to DPA (EPA: DPA) is less than about 1: 1. In some embodiments, the ratio of DHA: EPA is less than about 1: 1. In some embodiments, the composition further comprises heneicosapentaenoic acid (HPA) in an amount of at least 1% of the total amount of fatty acids.

  The present invention is a pharmaceutical composition comprising eicosapentaenoic acid (EPA) at a daily dose of about 1000 mg to about 5000 mg and further comprising docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), Pharmaceutical compositions comprising 5% or less DHA of the total amount of fatty acids and having a DHA: DPA ratio of 1: 1 or less and methods of using the compositions are provided. In some embodiments, the ratio of DHA: EPA is less than about 1:10. In some embodiments, the ratio of EPA: DPA is less than about 1: 1. In some embodiments, the composition further comprises heneicosapentaenoic acid (HPA) in an amount of at least 1% of the total amount of fatty acids.

  The present invention provides a pharmaceutical composition comprising eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA), wherein the amount of EPA and DPA is about 55% by weight or more of the total amount of fatty acids, And a DHA: DPA ratio of 1: 1 or less, and a method of using the composition. In some embodiments, the composition comprises docosahexaenoic acid (DHA) in an amount that is less than about 30% of the total amount of fatty acids. In some embodiments, the composition comprises a daily dose of DPA greater than about 120 mg / day. In some embodiments, the composition comprises ω6 fatty acids in an amount that is no more than 6% of the total amount of fatty acids. In some embodiments, the composition comprises DPA in an amount of at least 6% of the total amount of fatty acids.

  The present invention relates to docosapentaenoic acid (DPA) in an amount of about 50% to about 80% of the total amount of fatty acids, docosahexaenoic acid (DHA) in an amount of about 25% to about 40% of the total amount of fatty acids, and optionally fatty acids Pharmaceutical compositions comprising eicosapentaenoic acid (EPA) in an amount less than about 10% of the total amount of and a method of using the composition are provided. In some embodiments, the composition comprises about 50% to 75% of the total amount of fatty acids, alternatively about 50% to about 70%, alternatively about 50% to about 65%, or alternatively about 50% to about 60%. Contains docosapentaenoic acid (DPA) in an amount. In some embodiments, the composition comprises docosahexaenoic acid (DHA) in an amount of about 25% to about 38%, alternatively about 25% to about 35%, alternatively about 30% to about 35% of the total amount of fatty acids. . In some embodiments, the composition comprises eicosapentaenoic acid (in an amount of less than about 9%, alternatively less than about 8%, alternatively less than about 7%, alternatively less than about 6%, alternatively less than about 5% of the total amount of fatty acids. EPA).

  In some embodiments, the composition of the present invention is at least 50%, alternatively at least 55%, alternatively at least 60%, alternatively at least 65%, alternatively at least 70%, alternatively at least 75%, alternatively at least 80% of the total amount of fatty acids. Or at least 85%, alternatively at least 95% omega 3 fatty acids, most preferably at least 90% omega 3 fatty acids. In some embodiments, the composition comprises at least 92% to about 99%, alternatively about 93% to about 98%, alternatively about 94% to about 98%, omega 3 fatty acids of the total amount of fatty acids.

  In other embodiments, EPA and DPA are combined in the composition of the present invention from about 55% to about 100% of total fatty acids, alternatively from about 60% to about 100% of total fatty acids, alternatively from about 65% to about 100%. Or about 70% to about 100%, alternatively about 75% to about 100%, alternatively about 80% to about 100%, alternatively about 85% to about 95%, alternatively about 85% to about 100%, alternatively about 85% About 97%, alternatively about 88% to about 95%, alternatively about 88% to about 97%, alternatively about 88% to about 100%, alternatively about 90% to about 95%, alternatively about 90% to about 97%, Alternatively from about 90% to about 100%, alternatively from about 95% to about 100%, alternatively from about 97% to about 100%.

  The composition of the present invention is preferably 100 mg to 10,100 mg / day, alternatively 200 mg to 8,100 mg / day, alternatively 300 mg to 6,100 mg / day, alternatively 400 mg to 5,100 mg / day, or alternatively, on an EPA + DPA daily basis. It can be provided at a dose of 500 mg to 4,100 mg / day. In some embodiments, preferably on a EPA + HPA + DPA daily dosage basis, preferably 100 mg to 10,100 mg / day, alternatively 200 mg to 8,100 mg / day, alternatively 300 mg to 6,100 mg / day, alternatively 400 mg to 5,100 mg / day, Alternatively, it can be provided at a dose of 500 mg to 4,100 mg / day. In some embodiments, on a daily basis of ω3-pentaenoic acid, the methods and compositions of the present invention are preferably 100 mg to 10,100 mg / day, alternatively 200 mg to 8,100 mg / day, alternatively 300 mg to 6,100 mg / day, Alternatively, it may be provided at a dose of 400 mg to 5,100 mg / day, alternatively 500 mg to 4,100 mg / day.

  Fatty acids such as EPA and DPA can exist in free fatty acid form or as salts, esters, or derivatives. The fatty acids are preferably configured as triglycerides, esters (such as ethyl esters), or free fatty acids. Other forms of fatty acids that may be useful include metabolism of fatty acids (such as EPA and / or DPA), or uptake of fatty acids (such as EPA and / or DPA) into body fluids, tissues, or organs. Any type of salt obtained, any type of ester, amide, monoglyceride, diglyceride, or triglyceride, phospholipid, or any other form may be mentioned.

  The ω3 fatty acids can be grouped according to the number of double bonds contained in the fatty acid chain. For example, hexadecatrienoic acid (HTA), α-linolenic acid (ALA), and eicosatrienoic acid (ETE) are ω3-trienoic acids, and stearidonic acid (SDA) and eicosatetraenoic acid (ETA) are ω3-tetraenoic acid, EPA, heneicosapentaenoic acid (HPA), DPA, and tetracosapentaenoic acid (TPA) are ω3-pentaenoic acids, and DHA and tetracosahexaenoic acid (THA) are ω3- Hexaenoic acid. In some preferred embodiments, the term ω3-pentaenoic acid has a ratio of at least 1:25, more preferably at least 1:50, more preferably at least 1:75, more preferably at least 1: 100. Means a mixture of at least two ω 3 pentaenoic acids in a ratio, more preferably a ratio of at least 1: 125, more preferably a ratio of at least 1: 150, more preferably a ratio of at least 1: 200. In some embodiments, this ratio refers to the ratio of the most prevalent ω3 pentaenoic acid in the mixture to the most prevalent ω3 pentaenoic acid in the mixture.

  In some embodiments, the composition of the invention comprises EPA, HPA, DPA, and TPA, or EPA and DPA, or the composition of the invention comprises EPA, HPA, and DPA.

  In some embodiments, the ω3-pentaenoic acid in the composition of the present invention is 99.5% or less, alternatively 99% or less; alternatively 98.5% or less; alternatively 98% or less; alternatively 97.5% or less; alternatively 96% or less; 94% or less; or 93% or less; or 92% or less; or 91% or less; or 90% or less; or 88% or less; or 85% or less; or 80% or less; Or less; 65% or less; alternatively 60% or less; alternatively 55% or less; alternatively 50% or less; alternatively 45% or less; alternatively 40% or less; alternatively 30% or less, containing a single ω3-pentaenoic acid.

  In some embodiments, in the compositions of the invention, at least 10%, alternatively at least 20%, alternatively at least 25%, alternatively at least 35%, alternatively at least 50%, alternatively at least 60%, alternatively at least 65% by weight, alternatively at least 70% by weight, alternatively at least 75% by weight fatty acids comprise ω3-pentaenoic acid, its salts, esters or derivatives.

  In some embodiments, significant amounts of ω3-pentaenoic acid, or glycerin or ethyl esters thereof, can be used in the methods of the invention. In some embodiments, the compositions and methods comprise at least 100 mg ω3-pentaenoic acid per day, alternatively at least 200 mg ω3-pentaenoic acid per day, alternatively at least 300 mg ω3-pentaenoic acid per day, alternatively per day. At least 500 mg ω3-pentaenoic acid, alternatively at least 700 mg ω3-pentaenoic acid per day, alternatively at least 900 mg ω3-pentaenoic acid per day, alternatively at least 1000 mg ω3-pentaenoic acid per day, alternatively at least 1500 mg ω3-pentaenoic acid per day Acid, or at least 1900 mg ω3-pentaenoic acid per day, alternatively at least 2000 mg ω3-pentaenoic acid per day, alternatively at least 2500 mg ω3-pentaenoic acid per day, alternatively at least 2900 mg ω3-pentaenoic acid per day, alternatively at least per day 3000mg ω3-penta Acid, or at least 3500 mg ω3-pentaenoic acid per day, or at least 3900 mg ω3-pentaenoic acid per day, or at least 4000 mg ω3-pentaenoic acid per day, or at least 4100 mg ω3-pentaenoic acid per day, or per day At least 4500 mg ω3-pentaenoic acid, or at least 5000 mg ω3-pentaenoic acid per day, or at least 5500 mg ω3-pentaenoic acid per day, or at least 6000 mg ω3-pentaenoic acid per day, or at least 6100 mg ω3-pentaenoic acid per day Acids, or glycerin or ethyl esters thereof.

  In some embodiments, the composition has a DHA: N3-5 enoic acid FA ratio of 15: 1 or less compared to the amount of ω3-pentaenoic acid (N3-5 enoic FA). DHA: N3-5 enoic acid FA, or 12: 1 or less DHA: N3-5 enoic acid FA, or 10: 1 or less DHA: N3-5 enoic acid FA, or 8: 1 or less DHA: N3-5 enoic acid FA, or 5: 1 or less DHA: N3-5 enoic acid FA, or 3: 1 or less DHA: N3-5 enoic acid FA, or 2: 1 or less DHA: N3- 5 enoic acid FA, or 1: 1 or less DHA: N3-5 enoic acid FA, or 1: 2 or less DHA: N3-5 enoic acid FA, or 1: 3 or less DHA: N3-5 ene Acid FA, or 1: 5 or less DHA: N3-5 enoic acid FA, or 1: 8 or less DHA: N3-5 enoic acid FA, or 1:10 or less DHA: N3-5 enoic acid FA Or DHA: N3-5 enoic acid FA less than 1:15, or DHA: N3-5 enoic acid FA less than 1:20.

  In some embodiments, the composition of the invention comprises at least 0.01% HPA of total fatty acids in the composition, or at least 0.05% HPA, or at least 0.10% HPA, or at least 0.15% HPA, or at least 0.2. % HPA, or at least 0.3% HPA, or at least 0.4% HPA, or at least 0.5% HPA, or at least 0.75% HPA, or at least 1% HPA, or at least 1.5% HPA, or at least 2% HPA, or at least 2.5% HPA, or at least 3% HPA, or at least 3.5% HPA, or at least 4% HPA, or at least 4.5% HPA, or at least 5% HPA, or at least 6% HPA, or at least 7% HPA, or the composition of the invention comprises at least 9% HPA of total fatty acids in the composition. In some embodiments, the composition of the present invention comprises no more than 20% HPA of total fatty acids in the composition, or no more than 15% HPA, or no more than 12% HPA, or no more than 10% HPA, or 8% The following HPA, or 7% or less HPA, or 6% or less HPA, or 5% or less HPA, or 4% or less HPA, or 3% or less HPA, or 2% or less HPA, or 1.5% or less Or the composition of the present invention comprises at least 1% HPA of total fatty acids in the composition. In some embodiments, the compositions of the present invention comprise 1% to 20% HPA of total fatty acids in the composition. In some embodiments, the compositions of the invention have from about 1% to about 6% HPA, or from about 2% to about 5% HPA, or from about 3% to about 3% relative to the total amount of fatty acids in the composition. Contains 4% HPA. In some embodiments, the compositions of the invention have from about 10 mg / g to about 50 mg / g HPA, or from about 15 mg / g to about 45 mg / g, or from about 20 mg / g to about 40 mg / g, or about 25 mg. / g to about 35 mg / g, or about 30 mg / g HPA.

  In some embodiments, the present invention provides compositions and methods comprising a significant amount of ω3 heneicosapentaenoic acid (HPA) or a glycerin or ethyl ester thereof. In some embodiments, the method of treatment comprises subjecting a subject in need thereof to at least 10 mg HPA per day, alternatively at least 15 mg HPA per day, alternatively at least 20 mg HPA per day, alternatively at least 25 mg HPA per day, Or at least 30 mg HPA per day, or at least 40 mg HPA per day, or at least 50 mg HPA per day, or at least 60 mg HPA per day, or at least 70 mg HPA per day, or at least 80 mg HPA per day, or At least 90 mg HPA per day, or at least 100 mg HPA per day, or at least 120 mg HPA per day, or at least 150 mg HPA per day, or at least 160 mg HPA per day, or at least 180 mg HPA per day, or per day At least 200 mg HPA, or 1 day At least 250 mg HPA, or at least 300 mg HPA per day, or at least 350 mg HPA per day, or at least 400 mg HPA per day, or at least 500 mg HPA per day, or at least 600 mg HPA per day, or at least per day A dose of 800 mg of HPA3, or its glycerol ester or ethyl ester may be provided.

  In some embodiments, the composition of the present invention is 10% or less, or 9% or less, or 8% or less, or 7% or less, or 6% or less, or 5% or less, or 4.5% or less, or 4%. Or less, or 3.5% or less, or 3% or less, or 2.5% or less, or 2% or less, or 1.5% or less, or 1.25% or less, or 1% or less, or 0.75% or less, or 0.5% or less, or 0.4% Or 0.3% or less, or 0.2% or less of ω3 fatty acid that is not ω3-pentaenoic acid, or the composition of the present invention contains 0.1% or less of ω3 fatty acid that is not ω3-pentaenoic acid.

  In embodiments of the invention, the composition comprises EPA and DPA from 99: 1 to 1:99 EPA: DPA, or 90: 1 to 1:90, or 60: 1 to 1:60, or 60: 1 to 1. : 20, or 60: 1 to 1: 4, or 40: 1 to 1:20, or 30: 1 to 1:20, or 30: 1 to 1:10, or 30: 1 to 1: 5, or 40 : 1-1: 4, or 30: 1-1: 4, or 30: 1-1: 2, or 30: 1-1: 1, or 30: 1-2: 1, or 30: 1-5: 1, or 20: 1 to 1:20, or 20: 1 to 1:10, or 20: 1 to 1: 5, or 20: 1 to 1: 2, or 20: 1 to 1: 1, or 20: 1-2: 1, or 20: 1-5: 1, 20: 1-10: 1, 20: 1-10: 1, or 30: 1-10: 1, or 60: 1-10: 1 EPA: DPA ratio or include EPA and DPA in a 40: 1 to 10: 1 EPA: DPA ratio. In some embodiments, the ratio of EPA: DPA is greater than 1: 1, preferably greater than 2: 1, more preferably greater than 5: 1. In some embodiments, the ratio of EPA: DPA is 1: 1 to 25: 1, preferably 5: 1 to 20: 1, more preferably 8: 1 to 15: 1, and even more preferably 9: 1 to 13. : 1, more preferably about 10: 1 to 11: 1, most preferably about 10: 1.

  In some embodiments of the invention, the composition comprises EPA in an amount of 55% to 95% relative to the total amount of fatty acids present in the composition, or in the total amount of fatty acids present in the composition. 60% to 95%, or 65% to 95%, or 70% to 95%, or 75% to 95%, or 90% to 95%, or 80% to 95%, or 90% to 95%, Or 55% to 90%, or 60% to 90%, or 65% to 90%, or 70% to 90%, or 75% to 90%, or 80% to 90%, or 85% to 90%, or 55% -92%, or 60% -92%, or 65% -92%, or 70% -92%, or 75% -92%, or 80% -92%, or 85% -92%, or 55 % To 93%, or 60% to 93%, or 65% to 93%, or 70% to 93%, or 75% to 93%, or 80% to 93%, or 85% to 93%, or 85% Contains over, or over 85%, or 85% to 95% EPA. In some embodiments, the composition is about 70% to about 95%, 80% to about 90%, or about 81% to about 88%, or about 82% of the total amount of fatty acids present in the composition. % To about 88%, or about 83% to about 87%, or about 84% to about 86%, or about 85% EPA. In some embodiments, the composition comprises about 750 mg / g to about 950 mg / g, or about 800 mg / g to about 900 mg / g, or about 830 mg / g to about 870 mg / g, or about 840 mg / g to about 870 mg / g, or 845 mg / g to about 865 mg / g, or 846 mg / g to about 860 mg / g, or 847 mg / g to about 859 mg / g, or about 848 mg / g to about 858 mg / g, or about 849 mg / g About 857 mg / g, or about 850 mg / g to about 856 mg / g, or about 851 mg / g to about 855 mg / g, or about 852 mg / g to about 854 mg / g, or about 853 mg / g.

  The composition of the present invention is preferably 100 mg to 10,000 mg / day, or 200 mg to 8,000 mg / day, or 300 mg to 6,000 mg / day, or 400 mg to 5,000 mg / day, or 500 mg to 4,000 on an EPA daily basis. Provided in mg / day dose. In some embodiments, the compositions and methods of the present invention have about 1000 mg / day to about 5000 mg / day, or about 1200 mg / day to about 3000 mg / day, or about 1500 mg / day to about 2500 mg / day, or 1600 mg / day. From about 1950 mg / day, or from about 1735 mg / day to about 1855 mg / day, or from about 1740 mg / day to about 1840 mg / day, or from about 1745 mg / day to about 1820 mg / day, or from about 1750 mg / day to about 1800 mg / day Or about 1755 mg / day to about 1790 mg / day, or about 1760 mg / day to about 1780 mg / day, or about 1770 mg / day. In some embodiments, the compositions of the invention have from about 2300 mg / day to about 3000 mg / day, or from about 2400 mg / day to about 2800 mg / day, or from about 2520 mg / day to about 2780 mg / day, or about 2600 mg / day. About 2700 mg / day, or about 2610 mg / day to about 2680 mg / day, or about 2620 mg / day to about 2670 mg / day, or about 2630 mg / day to about 2665 mg / day, or about 2640 mg / day to about 2660 mg / day, Or provided at a dose of about 2650 mg / day of EPA. In some embodiments, the composition of the present invention has from about 3200 mg / day to about 3900 mg / day, or from 3300 mg / day to about 3800 mg / day, or from 3360 mg / day to about 3710 mg / day, or from about 3400 mg / day to about 3400 mg / day. 3700 mg / day, or about 3450 mg / day to about 3650 mg / day, or about 3500 mg / day to about 3600 mg / day, or about 3530 mg / day to about 3580 mg / day, or about 3540 mg / day to about 3560 mg / day, or about Provided at a dose of 3550 mg / day EPA.

  In some embodiments, the compositions of the invention have from about 1650 mg / day to about 2050 mg / day, or from about 1700 mg / day to about 2000 mg / day, or from about 1750 mg / day to about 1950 mg / day, or about 1775 mg / day. About 1925 mg / day, or about 1800 mg / day to about 1900 mg / day, or about 1800 mg / day to about 2000 mg / day, or about 1820 mg / day to about 1880 mg / day, or about 1830 mg / day to about 1870 mg / day, Or provided at a dose of EPA from about 1840 mg / day to about 1860 mg / day, or about 1850 mg / day. In some embodiments, the composition of the present invention has from about 2500 mg / day to about 3100 mg / day, or from about 2600 mg / day to about 2000 mg / day, or from about 2650 mg / day to about 2950 mg / day, or about 2700 mg / day. About 2900 mg / day, or about 2725 mg / day to about 2875 mg / day, or about 2750 mg / day to about 2850 mg / day, or about 2780 mg / day to about 2820 mg / day, or about 2790 mg / day to about 2810 mg / day, Or provided at a dose of about 2800 mg / day of EPA. In some embodiments, the compositions of the invention have from about 3300 mg / day to about 4000 mg / day, or from about 3400 mg / day to about 3900 mg / day, or from about 3500 mg / day to about 3900 mg / day, or about 3550 mg / day. About 3850 mg / day, or about 3600 mg / day to about 3800 mg / day, or about 3650 mg / day to about 3750 mg / day, or about 3680 mg / day to about 3725 mg / day, or about 3690 mg / day to about 3710 mg / day, Or provided at a dose of about 3700 mg / day of EPA.

  In some embodiments, the compositions of the present invention have about 1500 mg / day to about 2500 mg / day, or about 1750 mg / day to about 2300 mg / day, or about 1800 mg / day to about 2200 mg / day, or about 1900 mg / day. It is provided at a dose of EPA to about 2100 mg / day, or about 1950 mg / day to about 2050 mg / day, or about 1975 mg / day to about 2025 mg / day, or about 2000 mg / day. In some embodiments, the composition of the present invention has from about 2500 mg / day to about 3500 mg / day, or from about 2700 mg / day to about 3300 mg / day, or from about 2750 mg / day to about 3300 mg / day, or about 2800 mg / day. Provided at a dose of EPA to about 3200 mg / day, or about 2900 mg / day to about 3100 mg / day, or about 2950 mg / day to about 3050 mg / day, or about 2975 mg / day to about 3025 mg / day, or about 3000 mg / day Is done. In some embodiments, the compositions of the invention have from about 3500 mg / day to about 4500 mg / day, or from about 3700 mg / day to about 4300 mg / day, or from about 3750 mg / day to about 4300 mg / day, or about 3800 mg / day. Provided at a dose of EPA to about 4200 mg / day, or about 3900 mg / day to about 4100 mg / day, or about 3950 mg / day to about 4050 mg / day, or about 3975 mg / day to about 4025 mg / day, or about 4000 mg / day Is done.

  In other aspects of the invention, the composition comprises from 1% to 99% DPA to 1% to 99% of the total amount of fatty acids present in the composition, or from 1% to the total amount of fatty acids present in the composition. 95%, or alternatively 1% -90%, or 1% -85%, or 1% -80%, or 1% -75%, or 1% -70%, or 1% -65%, or 1 % -60%, or 1% -55%, or 1% -50%, or 1% -45%, or 1% -40%, or 1% -35%, or 1% -30%, or 1% ~ 25%, or 1% ~ 20%, or 1% ~ 15%, or 1% ~ 10%, or 1% ~ 5%, or 2% ~ 99%, or 2% ~ 95%, or 2% ~ 90%, or 2% to 85%, or 2% to 80%, or 2% to 75%, or 2% to 70%, or 2% to 65%, or 2% to 60%, or 2% to 55 %, Or 2% to 50%, or 2% to 45%, or 2% to 40%, or 2% to 35%, or 2% to 30%, or 2% to 25%, or 2% to 20% Or 2% to 15%, or 2% to 10%, or 2% to 5%, or 3% to 99% Or 3% to 95%, or 3% to 90%, or 3% to 85%, or 3% to 80%, or 3% to 75%, or 3% to 70%, or 3% to 65%, or 3% to 60%, or 3% to 55%, or 3% to 50%, or 3% to 45%, or 3% to 40%, or 3% to 35%, or 3% to 30%, or 3 % To 25%, or 3% to 20%, or 3% to 15%, or 3% to 10%, or 3% to 5%, or 4% to 99%, or 4% to 95%, or 4% ~ 90%, or 4% to 85%, or 4% to 80%, or 4% to 75%, or 4% to 70%, or 4% to 65%, or 4% to 60%, or 4% to 55%, or 4% -50%, or 4% -45%, or 4% -40%, or 4% -35%, or 4% -30%, or 4% -25%, or 4% -20 %, Or 4% to 15%, or 4% to 10%, or 4% to 5%, or 5% to 99%, or 5% to 95%, or 5% to 90%, or 5% to 85% Or 5% to 80%, or 5% to 75%, or 5% to 70%, or 5% to 65%, or 5% to 60%, or 5% to 55%, or 5% to 50%, Or 5% to 45%, or 5% to 40%, or 5% to 35%, or 5% to 30%, or 5% to 25%, or 5% to 20%, or 5% to 15%, Or 5% to 12%, or 5% to 10%, or 6% to 99%, or 6% to 95%, or 6% to 90%, or 6% to 85%, or 6% to 80%, or 6% -75%, or 6% -70%, or 6% -65%, or 6% -60%, or 6% -55%, or 6% -50%, or 6% -45%, or 6 % -40%, or 6% -35%, or 6% -30%, or 6% -25%, or 6% -20%, or 6% -15%, or 6% -12%, or 6% ~ 11%, or 6% ~ 10%, or 7% ~ 99%, or 7% ~ 95%, or 7% ~ 90%, or 7% ~ 85%, or 7% ~ 80%, or 7% ~ 75%, or 7% -70%, or 7% -65%, or 7% -60%, or 7% -55%, or 7% -50%, or 7% -45%, or 7% -40 %, Or 7% to 35%, or 7% to 30%, or 7% to 25%, or 7% to 20%, or 7% to 15%, or 7% to 12%, or 7% to 11% , Or 7% to 10%, or 8% to 99%, or 8% to 95%, or 8% to 90%, or 8% to 85%, or 8% to 80%, or 8% to 75%, Or 8% -70%, or 8% -65%, or 8% -60%, or 8% -55%, or 8% -50%, or 8% -45%, or 8% -40%, or 8% to 35%, or 8% to 30%, or 8% to 25%, or 8% to 20%, or 8% to 15%, or 8% to 12%, or 9% to 95%, or 9 % -90%, or 9% -85%, or 9% -80%, or 9% -75%, or 9% -70%, or 9% -65%, or 9% -60%, or 9% ~ 55%, or 9% -50%, or 9% -45%, or 9% -40%, or 9% -35%, or 9% -30%, or 9% -25%, or 9%- In an amount of 20%, or 9% to 15%, or 9% to 12%. In some embodiments, the composition comprises about 5% to about 15%, or about 6% to about 12%, or about about docosapentaenoic acid (DPA) relative to the total amount of fatty acids present in the composition. In an amount of 7% to about 11%, or about 8% to about 10%. In some alternative embodiments, the composition comprises at least about 4%, or at least about 5%, or at least about 6%, or at least about 7%, or at least about 8%, or at least about 9%, or at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50% Or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or At least about 95% docosapentaenoic acid (DPA).

  In some embodiments, the composition is about 60 mg / g to about 120 mg / g, alternatively about 70 mg / g to about 100 mg / g, 75 mg / g to about 90 mg / g, alternatively about 77 mg / g to about 85 mg / g, alternatively about 78 mg / g to about 84 mg / g, alternatively about 79 mg / g to about 83 mg / g, alternatively about 80 mg / g to about 82 mg / g, or Docosapentaenoic acid (DPA) is included in an amount of about 81 mg / g to about 82 mg / g. In some embodiments, the composition comprises at least about 20 mg / day, alternatively at least about 25 mg / day, alternatively at least about 30 mg / day, alternatively at least about 40 mg / day, alternatively at least about 50 mg / day, Alternatively at least about 60 mg / day, alternatively at least about 70 mg / day, alternatively at least about 75 mg / day, alternatively at least about 80 mg / day, alternatively at least about 90 mg / d day, alternatively at least about 100 mg / day, or alternatively At least about 120 mg / day, alternatively at least about 150 mg / day, alternatively at least about 160 mg / day, alternatively at least about 180 mg / day, alternatively at least about 200 mg / day, alternatively at least about 250 mg / day, alternatively at least about 300 mg / day, alternatively at least about 350 mg / day, alternatively at least about 400 mg / day, alternatively at least about 500 mg / day, alternatively at least about 600 mg / day, alternatively at least About 800 mg / day, alternatively at least about 1000 mg / day, alternatively at least about 1200 mg / day, alternatively at least about 1500 mg / day, alternatively at least about 2000 mg / day, alternatively at least about 3000 mg / day, alternatively at least about 3500 Contains docosapentaenoic acid (DPA) at a daily dose of mg / day, alternatively at least about 4000 mg / day, alternatively at least about 4250 mg / day. In some embodiments, the composition comprises from about 120 mg / day to about 150 mg / day, alternatively from about 150 mg / day to about 200 mg / day, alternatively from about 200 mg / day to about 250 mg / day, or About 250 mg / day to about 300 mg / day, alternatively about 300 mg / day to about 400 mg / day, alternatively about 400 mg / day to about 600 mg / day, alternatively about 600 mg / day to about 1000 mg / day Contains DPA at daily doses of In some embodiments, the treatment method comprises at least about 1 mg / kg docosapentaenoic acid (DPA) per day, or at least about 2 mg / kg DPA per day, or at least about 3 mg / kg per day. DPA, or at least about 4 mg / kg DPA per day, or at least about 6 mg / kg DPA per day, or at least about 8 mg / kg DPA per day, or at least about 10 mg / kg DPA per day, Or at least about 20 mg / kg DPA per day, or at least about 30 mg / kg DPA per day, or at least about 40 mg / kg DPA per day, or at least about 50 mg / kg DPA per day, Alternatively, a dose of at least about 75 mg / kg DPA per day, or at least about 100 mg / kg DPA per day is provided.

  In some embodiments, there is a relatively small amount of docosahexaenoic acid (DHA) compared to EPA. In some embodiments, the composition of the invention has a DHA: EPA of 1: 1 or less, or 1: 2 or less, or 1: 3 or less, or 1: 4 or less, or 1: 5 or less DHA: EPA, Or 1: 6 or less DHA: EPA, or 1: 7 or less DHA: EPA, or 1: 8 or less DHA: EPA, or 1: 9 or less DHA: EPA, or 1:10 or less DHA: EPA, Or 1:12 or less DHA: EPA, or 1:15 or less DHA: EPA, or 1:20 or less DHA: EPA, or 1:25 or less DHA: EPA, or 1:30 or less DHA: EPA, Or 1:40 or less DHA: EPA, or 1:50 or less DHA: EPA, or 1:75 or less DHA: EPA, or 1:90 or less DHA: EPA, or 1:99 or less DHA: EPA Including. Alternatively, DHA may be present in the composition of the present invention in a relative amount with a ratio of less than 1% to the amount of EPA. Alternatively, docosahexaenoic acid (DHA) may be present in the compositions of the present invention at a DHA: EPA ratio of less than 1:99.

  In some embodiments, there is a relatively small amount of docosahexaenoic acid (DHA) relative to the total amount of fatty acids present in the composition. In some embodiments, the compositions of the invention have 30% or less DHA, or 20% or less DHA, or 15% or less DHA, or 12% or less, relative to the total amount of fatty acids present in the composition. Or less than 10%, or less than 9%, or less than 8%, or less than 7%, or less than 6%, or less than 5%, or less than 4% Contains DHA, or 3% or less DHA, or 2% or less DHA, or 1% or less DHA. In some embodiments, the compositions and methods comprise a total daily dose of less than 1500 mg DHA, alternatively less than 1200 mg, alternatively less than 1000 mg DHA, alternatively less than 800 mg DHA, alternatively less than 700 mg DHA, alternatively 600 mg Less than DHA, or less than 500 mg DHA, or less than 400 mg DHA, or less than 350 mg DHA, or less than 300 mg DHA, or less than 250 mg DHA, or less than 200 mg DHA, or less than 150 mg DHA, or less than 120 mg DHA or less than 100 mg DHA or less than 80 mg DHA or less than 60 mg DHA or less than 40 mg DHA or less than 30 mg DHA or less than 25 mg DHA or less than 20 mg DHA or its glycerin ester or ethyl Contains esters.

  In some embodiments, the composition has from about 5 mg / g to about 20 mg / g, or from about 8 mg / g to about 18 mg / g, or from about 9 mg / g to about 15 mg / g, or from about 10 mg / g to about 14 mg / g, or about 11 mg / g to about 13 mg / g, or about 12 mg / g to about 13 mg / g docosahexaenoic acid (DHA).

  In some embodiments, the ratio of EPA: HPA is about 1500: 1-25: 1, or 1000: 1-50: 1, or 800: 1-60: 1, or 500: 1-60: 1, or 250: 1 to 75: 1 and / or 100: 1 to 80: 1. In some preferred embodiments, the ratio of EPA: HPA is about 85: 1. In some preferred embodiments, the ratio of EPA: HPA is about 30: 1. In some embodiments, the ratio of DPA: HPA is about 250: 1 to 1: 1, or 200: 1 to 2: 1, or 150: 1 to 3: 1, or 100: 1 to 4: 1, or 50: 1 to 5: 1, or 25: 1 to 6: 1, or 10: 1 to 7: 1. In some preferred embodiments, the ratio of DPA: HPA is about 8: 1. In some embodiments, the ratio of DPA: HPA is about 3: 0.

  In other embodiments, there is a relatively small amount of DHA compared to DPA. In these embodiments, the compositions of the present invention comprise 15: 1 or less DHA: DPA, or 12: 1 or less DHA: DPA, or 10: 1 or less DHA: DPA, or 8: 1 or less DHA: DPA. , Or 5: 1 or less DHA: DPA, or 4: 1 or less DHA: DPA, or 3: 1 or less DHA: DPA, or 2: 1 or less DHA: DPA, or 1: 1 or less DHA: DPA Or 1: 2 or less DHA: DPA or 1: 3 or less DHA: DPA or 1: 4 or less DHA: DPA or 1: 5 or less DHA: DPA or 1: 6 or less DHA: DPA Or 1: 7 or less DHA: DPA, or 1: 8 or less DHA: DPA, or 1:10 or less DHA: DPA, or 1:12 or less DHA: DPA, or 1:15 or less DHA: DPA , Or 1:20 or less DHA: DPA, or 1:25 or less DHA: DPA, or 1:50 or less DHA: DPA, or 1:75 or less DHA: DPA, or 1:90 or less DHA: DPA Or DHA: DPA of 1:95 or less, or DHA: DPA of 1: 100 or less. In some embodiments, the ratio of DHA: DPA is preferably less than 2: 1.

  In other embodiments, there is a relatively small amount of DHA compared to HPA. In these embodiments, the composition of the present invention comprises 15: 1 or less DHA: HPA, or 12: 1 or less DHA: HPA, or 10: 1 or less DHA: HPA, or 8: 1 or less DHA: HPA. Or, 5: 1 or less DHA: HPA, or 3: 1 or less DHA: HPA, or 2: 1 or less DHA: HPA, or 1: 1 or less DHA: HPA, or 1: 2 or less DHA: HPA Or 1: 3 or less DHA: HPA, or 1: 5 or less DHA: HPA, or 1: 8 or less DHA: HPA, or 1:10 or less DHA: HPA, or 1:15 or less DHA: HPA Or 1:20 or less DHA: HPA, or 1:25 or less DHA: HPA, or 1:50 or less DHA: HPA, or 1:75 or less DHA: HPA, or 1:90 or less DHA: HPA Or DHA: HPA of 1:95 or less, or DHA: HPA of 1: 100 or less.

  In yet another aspect, the composition of the present invention comprises 10% or less ω6 fatty acid relative to the total amount of fatty acids, or 9% or less, or 8% or less, based on the total amount of fatty acids included in the composition of the present invention, or 7% or less, or 6% or less, or 5% or less, or 4.5% or less, or 4% or less, or 3.5% or less, or 3% or less, or 2.5% or less, or 2% or less, or 1.7% or less, or Contains 1.5% or less, or 1.2% or less, or 1% or less, or 0.5% or less ω6 fatty acid.

  ω6 fatty acids include linoleic acid (LA; C18: 2-n6); γ-linolenic acid (GLA; C18: 3-n6); eicosadienoic acid (C20: 2-n6); dihomoγ-linolenic acid (DGLA; C20: 3-n6); arachidonic acid (ARA; C20: 4-n6); and ω6 docosapentaenoic acid (DPA; C22: 5-n6), but are not limited thereto.

  In a further aspect, the composition of the present invention comprises 10% or less of ω6 fatty acid based on the total amount of ω3 fatty acid and ω6 fatty acid, or 9% or less based on the total amount of ω3 fatty acid and ω6 fatty acid contained in the composition of the present invention. Or 8% or less, or 7% or less, or 6% or less, or 5% or less, or 4.5% or less, or 4% or less, or 3.5% or less, or 3% or less, or 2.5% or less, or 2% or less, Or 1.7% or less, or 1.5% or less, or 1.2% or less, or 1% or less, or 0.5% or less of ω6 fatty acid.

  In yet another embodiment, the composition of the present invention comprises 8% or less arachidonic acid (ARA; C20: 4-n6) relative to the total amount of ω3 fatty acid and ω6 fatty acid, or the ω3 fatty acid contained in the composition of the present invention. 7% or less, or 6% or less, or 5% or less, or 4.5% or less, or 4% or less, or 3.5% or less, or 3% or less, or 2.5% or less, or 2% or less of the total amount of ω6 fatty acids Or 1.7% or less, or 1.5% or less, or 1.2% or less, or 1% or less, or 0.5% or less of arachidonic acid (ARA; C20: 4-n6).

  In some embodiments, the total amount of fatty acids present in the composition in a total other than EPA, ETA, HPA, and DPA (or shown as the total of non-EPA, non-ETA, non-HPA, and non-DPA ω3 fatty acids). There are relatively small amounts of ω3 fatty acids. In some embodiments, the composition of the present invention comprises no more than 20% non-EPA, non-ETA, non-HPA, and non-DPA omega 3 fatty acids, or 15 in total, relative to the total amount of fatty acids present in the composition, or 15 % Non-EPA, non-ETA, non-HPA, and non-DPA omega-3 fatty acids, or 12% non-EPA, non-ETA, non-HPA, and non-DPA omega-3 fatty acids, or 10% non-EPA, non-ETA , Non-HPA, and non-DPA omega-3 fatty acids, or up to 8% non-EPA, non-ETA, non-HPA, and non-DPA omega-3 fatty acids, or up to 7% non-EPA, non-ETA, non-HPA, and non-DPA ω3 fatty acids, or 6% or less non-EPA, non-ETA, non-HPA, and non-DPA ω3 fatty acids, or 5% or less non-EPA, non-ETA, non-HPA, and non-DPA ω3 fatty acids, or 4% or less Non-EPA, non-ETA, non-HPA, and non-DPA ω3 fatty acids, or 3% or less non-EPA, non-ETA, non-HPA, and non-DPA ω3 fatty acids, or 2% or less, non-EPA, non-ETA, non-HPA , And non-DPA ω3 fatty acids Or containing less than 1% of the non-EPA, non ETA, the ω3 fatty acid of the non-HPA, and non-DPA.

  In some embodiments, there is a relatively small sum of ALA, SDA, and DHA relative to the total amount of fatty acids present in the composition, while a large amount of EPA, DPA-n3, HPA, and ETA Exists. In some embodiments, the composition of the present invention comprises no more than 20% total of ALA, SDA, and DHA, or no more than 15% ALA, SDA, and DHA, relative to the total amount of fatty acids present in the composition. Total, or up to 12% total of ALA, SDA, and DHA, or up to 10% total of ALA, SDA, and DHA, or up to 8% total of ALA, SDA, and DHA, or up to 7% ALA , SDA, and DHA, or 6% or less of ALA, SDA, and DHA, or 5% or less of ALA, SDA, and DHA, or 4% or less of ALA, SDA, and DHA, Or a total of up to 3% ALA, SDA, and DHA, or up to 2% total ALA, SDA, and DHA, or up to 1% total ALA, SDA, and DHA at the same time in the composition More than 40% EPA, DPAn-3, HPA, and ETA, or more than 50% EPA, DPAn-3, HPA, and ETA, or more than 60% EPA, relative to the total amount of fatty acids present Sum of DPAn-3, HPA, and ETA, or more than 70% EPA, DPAn-3, HPA, and ETA, or more than 75% EPA, DPAn-3, HPA, and ETA, or 80% Total of over EPA, DPAn-3, HPA, and ETA, or over 85% of EPA, DPAn-3, HPA, and ETA, or over 90% of EPA, DPAn-3, HPA, and ETA Or more than 95% EPA, DPAn-3, HPA and ETA, or 80% to 98% EPA, DPAn-3, HPA and ETA, or 80% to 96% EPA, DPAn- 3, the sum of HPA and ETA, or 85% to 98% of EPA, DPAn-3, HPA, and ETA, or 85% to 96% of EPA, DPAn-3, HPA, and ETA, or 90% -98% EPA, DPAn-3, HPA, and ETA total, or 90% -97% EPA, DPAn-3, HPA, and ETA total, or 90% -96% EPA, DPAn- 3. Contains the sum of HPA and ETA, or 90% to 95% of EPA, DPAn-3, HPA and ETA.

  In a further aspect, the composition of the present invention comprises 8% or less arachidonic acid (ARA; C20: 4-n6) based on the total amount of fatty acids, or 7% or less based on the total amount of fatty acids included in the composition of the present invention. Or 6% or less, or 5% or less, or 4.5% or less, or 4% or less, or 3.5% or less, or 3% or less, or 2.5% or less, or 2% or less, or 1.7% or less, or 1.5% or less Or 1.2% or less, or 1% or less, or 0.5% or less of arachidonic acid (ARA; C20: 4-n6).

  In another embodiment, the composition of the present invention comprises 2.5% or less arachidonic acid (ARA; C20: 4-n6), 0.4% or less ω6-docosapentaene relative to the total amount of fatty acids included in the composition of the present invention. Acid (DPA; C22: 5-n6) and 0.2% or less of γ-linolenic acid (GLA; C18: 3-n6).

  Further embodiments include: 2.5% or less arachidonic acid (ARA; C20: 4-n6), 0.3% or less ω6 docosapentaenoic acid (DPA; C22: 5-n6) based on the total amount of fatty acids included in the composition of the present invention. ), And 0.1% or less of γ-linolenic acid (GLA; C18: 3-n6).

  In some embodiments, the composition of the present invention further comprises TPA at a concentration of at least 0.05%. In some embodiments, the TPA concentration is about 0.01% to about 5%, or about 0.05% to about 2%, or about 0.1% to about 1%, or about 0.2% to about 0.8%, or about 0.4% to about 0.6%, or about 0.5%.

  The composition of the present invention may be taken as a general dietary supplement.

  In yet other embodiments, the active ingredients of the formulations of the present invention are essentially entirely from EPA and DPA or precursors thereof (ethyl ester, triglyceride, or any other pharmaceutically acceptable salt or derivative thereof). become. In that case, a non-major amount (preferably less than 15%, or less than 12%, or less than 10%, or less than 9%, or less than 8%, or less than 7%, or less than 6%, or less than 5%, or Less than 4%, or less than 3%, or less than 2%, or less than 1%, or less than 0.5%, or less than 0.25%).

  In a further aspect, the active ingredient of the formulation of the present invention is essentially complete from ω3-pentaenoic acid or a precursor thereof (ethyl ester, triglyceride, or any other pharmaceutically acceptable salt or derivative thereof). . In that case, a non-major amount (preferably less than 15%, or less than 12%, or less than 10%, or less than 9%, or less than 4%, or less than 4%, or less than 4%, or less than 4%, or Less than 4%, or less than 3%, or less than 2%, or less than 1%, or less than 0.5%, or less than 0.25%).

  The percentage of fatty acids is determined on a weight / weight, mole / mole, or chromatographic area percent basis for all fatty acids present in the composition, and the European Pharmacopoeia monograph for ω3 fatty acid concentrate, 90% ω3 acid ethyl ester European pharmacopoeia monograph on, or European pharmacopoeia monograph method 2.4.29, USP monograph on fish oil supplements, USP 35ω3 acid ethyl ester (LOVAZA®) monograph, etc. Determined by any essentially equivalent method (whether by gas chromatography, by HPLC, by FPLC, or by any other chromatographic method).

  In some embodiments, the percentage of fatty acids is not determined as a percentage of all fatty acids present in the composition, but as a specific type of fatty acid ethyl ester, all fatty acid ethyl esters present in the composition. From the determination of the percentage of fatty acids, for example in free fatty acids; monoglycerides, diglycerides, and triglycerides; or in phospholipids (such as phosphatidylserine or phosphatidylcholine) or polysorbates (such as Tween 80, Tween 20, or polysorbate 40) Fatty acids present such as fatty acids present in are excluded.

  In other embodiments, the percentage of fatty acids is not determined as a percentage of all fatty acids present in the composition, but as a percentage of all free fatty acids present in the composition as a particular type of free fatty acid. From the determination of the percentage of fatty acids and therefore present in eg fatty acid ethyl esters; monoglycerides, diglycerides and triglycerides; or phospholipids (such as phosphatidylserine or phosphatidylcholine) or polysorbates (such as Tween 80, Tween 20, or polysorbate 40) Fatty acids present, such as fatty acids to be eliminated.

  In yet another aspect, the percentage of fatty acids is not determined as a percentage of all fatty acids present in the composition, but as all types of glycerin fatty acid esters present in the composition as a particular type of glycerin fatty acid ester. The fatty acid present in the phospholipid (such as phosphatidylserine or phosphatidylcholine) or polysorbate (such as Tween 80, Tween 20, or polysorbate 40), for example, from the determination of the percentage of fatty acids Existing fatty acids such as are excluded.

  In a further aspect, the percentage of fatty acids is not determined as a percentage of all fatty acids present in the composition, but as all diglycerides and trifatty acid esters with glycerin and all glycerin di and glycerin present in the composition. From the determination of the percentage of fatty acids, and thus from the determination of the percentage of fatty acids, eg glycerin monofatty acid esters; fatty acid ethyl esters; free fatty acids; Fatty acids present such as those present in polysorbate 40) are excluded.

  In yet another aspect, the percentage of fatty acids is not determined as a percentage of all fatty acids present in the composition, but as all trifatty acid esters with glycerin, all glycerin trifatty acid esters present in the composition. Thus, from the determination of the percentage of fatty acids, for example, mono and di fatty acid esters of glycerol; fatty acid ethyl esters; free fatty acids; or phospholipids (such as phosphatidylserine or phosphatidylcholine) or polysorbates (Tween 80, Tween 20, or Fatty acids present such as those present in polysorbate 40) are excluded.

  EPA, HPA, DPA, or ω3-pentaenoic acid can be derived from any suitable source, including plant seed oil, microbial oil from algae or fungi, or marine oil from fish or other marine animals. Certain species are particularly excellent raw materials for oils containing DPA, such as seal oils. They may be used in the form of natural oils if they meet the purity requirements required by the present invention, or may be refined to yield a product containing the fatty acid composition of the present invention. .

  The composition of the present invention can be produced by a series of methods. Such methods include distillation including short path distillation; urea precipitation; enzyme conversion concentration; conventional chromatography; HPLC / FPLC; supercritical carbon dioxide extraction; supercritical carbon dioxide chromatography; Examples include supercritical carbon dioxide simulated moving bed chromatography; or chemical conversion methods such as iodolactonization. Such methods are generally known to those skilled in the art of purifying and isolating ω3 fatty acids.

  Usually, to separate ω3 fatty acids from other fatty acids covalently bonded together in the natural triglyceride molecule of the feedstock, the fatty acids contained in the marine oil feedstock (such as crude fish oil) are esterified with ethanol in order to separate the ω3 fatty acids. (This forms a fatty acid ethyl ester). The material can then be distilled once or several times to obtain a ω3 acid ethyl ester concentration of 60% to more than 70%. Alternatively, ω3 levels of 70% to over 90% can be reached by using enzyme concentration, urea precipitation, or supercritical extraction alone or in combination with distillation. To prepare a highly pure concentrate of a single ω3 fatty acid, usually chromatography, supercritical chromatography, simulated moving bed chromatography, supercritical simulated moving bed chromatography, or iodolactonization, etc. Methods such as chemical conversion methods are more than 50%, or more than 60%, or more than 70%, or more than 80%, or 90% of a single omega-3 fatty acid such as ETA, EPA, HPA, DPA, TPA, or DHA Most practical in reaching levels above% or above 95%.

  One skilled in the art will be able to design a suitable process to prepare a particular ω3 fatty acid composition as desired based on the above methods. Such a process is so flexible that it can affect the relative proportions between naturally occurring long chain C18, C20, C21, and C22 fatty acids in available fish oil feedstocks and other marine oils. Thereby not only is the concentration of individual ω3 fatty acids provided, but the ratio between them also remains within the pattern of variation caused by variations in nature. However, the preferred method corrects for extreme variations that may occur naturally. Thus, one skilled in the art will be able to make a product with a constant and predetermined composition.

  EPA is relatively abundant in fish oil or other marine oils and can be relatively easily obtained from such fish oils or marine oils by application of concentration and refining techniques. DPA and HPA are present at much lower concentrations. To prepare the composition of the present invention, DPA or HPA can be concentrated and purified from fish oil or other marine oil, either alone or in combination with DPA and EPA and / or HPA, according to the methods mentioned above. it can. Alternatively, DPA or HPA can be extracted from a high purity EPA concentrate by extension of the EPA fatty acid chain (C2 extension or C1 extension) with 2 or 1 hydrogen-saturated carbon on the carboxyl side of the molecule (eg Kuklev DV and Smith WL in Chem Phys Lipids, 2006; 144 (2): by methods similar to those described in 172-177, or by alternative methods with equivalent results). In another alternative approach, the present invention involves partial conversion of high purity EPA concentrate to DPA (or HPA) using a method for EPA C2 extension (or C1 extension) similar to that described above. Or an intermediate thereof can be obtained directly.

  Once oils containing one or more desired fatty acids are obtained and refined as necessary, these oils can be obtained in the desired relative amounts of EPA, DPA, HPA, DHA, TPA, other ω3 fatty acids, and ω6. By blending so as to obtain fatty acids, the composition of the present invention described in detail above can be obtained.

  Fish oil may contain by-products and contaminants such as pesticides, chlorinated or brominated hydrocarbons, heavy metals, cholesterol, and vitamins. During the production of the concentrate, the concentration of these components is significantly reduced compared to untreated fish oil. Such a reduction is inherent in the nature of purification methods and their ability to remove other compounds by concentrating some or specific ω3 fatty acids.

  Triglycerides containing more than 60% omega 3 fatty acids in the composition can be produced from ethyl esters and glycerin by well-known, public, or alternative chemical synthesis or enzymatic procedures. The free acid can be produced from the ethyl ester by well known hydrolysis or saponification procedures. Methods for converting ethyl esters to triglycerides, free fatty acids, and other molecular forms containing fatty acids are commonly used by those skilled in the art to chemically or enzymatically convert ω3 fatty acids from one form to another. It is known.

  In some embodiments, the composition of the invention comprises EPA, HPA, DPA, DHA, EPA + DHA, EPA + DPA, or the sum of EPA + HPA + DPA, total ω3-pentaenoic acid, or total ω3 in a mammal. It has improved pharmacological characteristics, as shown by the improved bioavailability of fatty acids. The main parameters for determining bioavailability are the maximum concentration (Cmax) of the therapeutic compound or its metabolite; the time from administration to maximum concentration (Tmax); and the area under the concentration curve over time) (AUC). Such parameters can be determined based on single dose or multiple dose dosing regimens. Methods for determining comparative bioavailability in mammals are generally known to those skilled in the art.

  Dietary conditions during administration of an ω3 fatty acid composition or ω3 fatty acid formulation to a subject may be particularly important for absorption and bioavailability of ω3 fatty acids. Commonly considered dietary conditions are fasting (no meals 8-12 hours before treatment administration and 2-3 hours after treatment administration); low fat diet (usually immediately before or after treatment administration, usually in the range of 15-30 minutes) Typically consume less than 25 grams of fat [350-600 Kcal]; or high fat diet (usually 40 grams to 75 grams of fat [usually immediately before or after treatment administration in the range of 15 to 30 minutes [ 700 to 1000 Kcal] containing a meal).

  In some embodiments of the invention, the time to reach the maximum concentration of EPA, DPA, DHA, EPA + DPA, EPA + DHA, total ω3-pentaenoic acid, or total ω3 fatty acid in blood, serum, or plasma The composition of the present invention is more rapidly absorbed as measured by (Tmax). In preferred embodiments of the invention, the Tmax under high fat diet conditions is less than 8 hours, or less than 6 hours, or about 5 hours, or 4 hours or less. In other preferred embodiments of the invention, the Tmax under low fat diet conditions is less than 8 hours, or less than 6 hours, or about 5 hours, or 4 hours or less. In yet another preferred embodiment of the invention, the Tmax under fasting conditions is less than 8 hours, or less than 6 hours, or about 5 hours, or 4 hours or less.

  In yet another aspect of the invention, for EPA, DPA, DHA, EPA + DPA, EPA + DHA, or total ω3 fatty acids under high fat diet conditions, under low fat diet conditions, and fasting conditions. Tmax is the Tmax for EPA, DPA, DHA, EPA + DPA, EPA + DHA, total ω3-pentaenoic acid, or total ω3 fatty acids for AMR101 or less. Finally, in other embodiments of the invention, the Tmax for EPA, DPA, DHA, EPA + DPA, EPA + DHA, or total ω3 fatty acids under the administration conditions of a low fat diet, fasting, or both is AMR101 Less than Tmax for EPA + DHA and EPA, DPA, DHA, EPA + DPA, EPA + DHA, or total ω3 fatty acids.

  In some embodiments, the above bioavailability characteristics improved relative to the above reference comparative product or a substantially equivalent form thereof become apparent upon administration of a single dose of a formulation according to the invention. However, in other embodiments, the above-described improved bioavailability characteristics become apparent after multiple dose administration.

  In another embodiment, the compositions of the present invention are more potent and effective than other ω3 compositions known in the prior art, such as LOVAZA®, EPANOVA®, or VASCEPA®.

  The formulation may be a single daily preparation to give the above intake in a single dose, conveniently divided doses such as 300-1500 mg each of EPA, EPA + DPA, EPA + It may be a daily dose formed from 2 to 4 soft gelatins or other dosage forms containing DPA + HPA, or omega-3 pentaenoic acid in any form embodied in the present invention .

  For example, flavoring or emulsifying agents may be included to make the preparation palatable. Other conventional additives, diluents, and excipients may be present. Preparations for oral consumption can be in the form of capsules, dry powders, tablets, solutions, oils, emulsions, or any other suitable form. The capsule can be a hard or soft gelatin capsule, an agar capsule, or any other suitable capsule.

  The use of the formulations of the invention in the manufacture of a medicament for the treatment or prevention of any disease or disorder, including those mentioned above, is included herein.

  The ω3 fatty acid composition may include a chemical antioxidant, such as α-tocopherol, administered in pure form or suspended in a vegetable oil, such as in soybean oil or corn oil.

  The mixed fatty acid composition is then converted into any suitable dosage form for oral, enteral, parenteral, rectal, vaginal, transdermal, or other routes of administration. Can be incorporated. Soft or hard gelatin capsules, flavored mixed oils, emulsifiers or other liquid forms, and microencapsulated powders or other dry form vehicles are all suitable ways of administering the product.

  As is known in the art, a formulated final drug product containing an ω3 fatty acid composition can be dispersed in a beverage, in capsules, tablets, or beverages to a mammal or patient in need thereof. Or in another solid oral dosage form, in liquid form, in soft gel capsules, or other convenient dosage forms such as oral liquid form in capsules. In some embodiments, the capsule comprises hard gelatin. The combination product may be contained in a liquid suitable for injection or infusion.

  Exemplary pharmaceutical grade finished dosage forms: (a) Soft or hard gelatin capsules containing 500 mg or 1000 mg of a mixture of 20 parts EPA as free fatty acid and 1 part DPA as free fatty acid respectively; (b) EPA And DPA free fatty acids are replaced with any other suitable bioassimilable form of fatty acids such as ethyl esters, but similar to (a); (c) the material can be used as a powder or in tablets It is in the form of a compressible microencapsulated powder, but similar to (a)-(b). Such powders can be prepared by various techniques known to those skilled in the art. (D) The formulation is a liquid or emulsion appropriately flavored for palatable oral administration, but as in (a)-(b); (e) the material is a cream or ointment, etc. As in (a)-(b), but formulated into a pharmaceutically acceptable vehicle suitable for topical application.

  The ω3 composition of the invention may be administered with a combination of one or more non-pharmaceutically active ingredients (also commonly known herein as “excipients”). Non-active ingredients are protected, for example, active ingredients can be solubilized, suspended, thickened, diluted, emulsified, stabilized, stored. To make an applicable and effective preparation that is safe to use, to color, to flavor, and to be safe, convenient and otherwise acceptable . Thus, non-active ingredients include colloidal silicon dioxide, crospovidone, lactose monohydrate, lecithin, crystalline cellulose, polyvinyl alcohol, povidone, sodium lauryl sulfate, sodium stearyl fumarate, talc, titanium dioxide, and xanthan gum. Can do.

  As used herein, the term “pharmaceutically acceptable vehicle” includes any of the following: a first API and optional other ingredients are solubilizing agents (eg, pharmaceutically acceptable). Solution completely dissolved in the solvent or solvent mixture, which remains in a clear liquid form near room temperature; a suspension; an oil; or a first API and optional other ingredients Semi-solid, completely or partially dissolved in suspensions, creams, etc.

  As used herein, a “pharmaceutical grade finished dosage form” is a unit dosage form suitable for administration to, for example, a human or animal subject and having content uniformity acceptable to regulatory authorities. Can be interpreted as For example, based on USP requirements for content uniformity, pharmaceutical grade finished dosage forms have an API amount in the range of 85% to 115% of the desired dose, and an RSD of less than 6.0% or 6.0%. Should have. In addition, the pharmaceutical grade finished dosage form has a pharmaceutically acceptable period, preferably at least 6 months when stored at room temperature (about 23 ° C. to 27 ° C., preferably about 25 ° C.) and 60% relative humidity. It must be stable for a period of at least 1 year, or at least 2 years (ie have a “validity period”). Usually, stability is determined by physical appearance and / or chemical modification of the components according to criteria well known in the pharmaceutical art, including those documented in ICH guidelines.

  Omega 3 fatty acid dosage forms may include chemical antioxidants such as alpha tocopherol, oils such as soybean oil and partially hydrogenated vegetable oil, and lubricants such as coconut oil, lecithin, and mixtures thereof.

  The composition of the present invention is effective for a subject in need thereof, eg, a subject susceptible to or afflicted with a disease or condition, or a subject in need of treatment of a disease or condition. Can be used to treat patients. The present invention provides a method of treating, preventing, and alleviating a symptom, lesion, or event associated with a disease or condition comprising administering any of the compositions of the present invention. The present invention relates to a method of treating symptoms associated with coronary heart disease (CHD), vascular disease, arteriosclerotic disease or related conditions, preventing the symptoms, reducing the occurrence of the symptoms, and reducing the symptoms I will provide a. The present invention also treats a symptom, lesion, or event associated with a vascular-related disease or condition, prevents the symptom, the lesion, or the event, and the occurrence of the symptom, the lesion, or the event. Also provided are methods of reducing and reducing the symptoms, the lesion, or the event. Examples of vascular diseases include, but are not limited to: atherosclerosis, atherosclerosis associated with hypercholesterolemia, hypertriglyceridemia or mixed dyslipidemia, coronary heart disease ( CHD), vascular disease, peripheral arterial disease (PAD), heart failure, cardiac arrhythmia, blood clotting status associated with cardiac arrhythmia, hypertension (including postoperative deep vein thrombosis or other high risk thrombotic conditions Coagulation related disorders, nephropathy and other kidney diseases, nephropathy, retinopathy, cognitive impairment, dementia (including but not limited to ischemic dementia and vascular dementia), and metabolic syndrome. The composition of the present invention is a subject or subject in need thereof, such as a subject susceptible to or suffering from a vascular / cardiovascular disease or condition, a subject at risk of causing a vascular / cardiovascular event, or By administering an effective amount of such a composition to a subject in need of treatment for a cardiovascular disease or condition, it can be used to treat a patient.

  Methods for determining such cardiovascular diseases / cardiovascular conditions and preventing events / symptoms in mammals and determining treatment and prophylactic / therapeutic effects are generally known to those skilled in the art.

  Administration of a composition of the present invention to a subject or treatment of a subject with a composition of the present invention results in a significant clinical improvement including but not limited to the following. In some embodiments, the invention provides for cardiac events or symptoms, and / or cardiovascular events or symptoms, for prevention of death, including death, cardiovascular death, and everything that causes cardiac death, And / or for the treatment and / or prevention of vascular events or symptoms. In some aspects, the present invention is also provided to reduce the number or frequency of such events, as well as the reduction or amelioration of symptoms associated with such events. Vascular events, cardiovascular events and / or cardiac events include, but are not limited to: death from cardiovascular events (including cardiovascular and cardiac death, etc.), sudden cardiac death, myocardial infarction (Fatal or non-fatal), ischemic heart attack, ischemic attack, angina, stroke, transient ischemic attack, thrombosis, deep vein thrombosis, pulmonary embolism, coronary revascularization, stent placement Coronary revascularization, carotid revascularization, stented carotid revascularization, peripheral arterial revascularization, stented peripheral arterial revascularization, major coronary events, coronary artery bypass grafting, other vascular grafts, aneurysm treatment, plaque Failure and hospitalization for cardiovascular events (including angina, acute and unstable angina). Cardiovascular events and / or cardiac events may also include other events that are deemed to fall within such categories by those skilled in the art. Study endpoints may include individual events or a combination of several events described directly above (for which the Major Adverse Cardiovascular Events or MACE are often used).

  In some embodiments, the present invention provides a method of delaying the process of atherosclerosis or improving the process of vascular healing in response to the presence of an atherogenic disease. Such delay or healing may include a decrease in stenosis and / or restenosis over time at a particular vascular site, a decrease or smaller increase in arterial wall intima complex thickness (IMT) over time, stenosis or It can be demonstrated by increasing lumen size and / or increasing vessel diameter over time at a vascular site with clot development. Such delays or cures include intravascular ultrasound (IVUS), radiography, echocardiography, radiology, non-invasive ultrasound, tomography, magnetic resonance interference (MRI), Or it can be determined by other acceptable methods. In other aspects, such delayed or improved healing can be demonstrated by a vessel wall composition, such as a reduced presence of foam cells in the vessel wall or a reduction in fibrillar tissue. In yet other embodiments, such improved vascular healing is demonstrated by improved inflammatory markers in the vessel wall or specific types of staining of vascular tissue.

  In some embodiments, the compositions of the present invention can differentially modify the ratio of platelets and fragments thereof (also known as platelet microparticles). Such fragments may be evaluated as a whole or may be investigated and described as a subclass of fragments.

  In some embodiments, the compositions of the invention can differentially modify the surface charge of platelets and fragments thereof in a quiescent state (non-activated platelets) or an activated state.

  In some embodiments, the compositions of the invention can affect the coagulation cascade and differentially modify clotting time or bleeding time or platelet aggregation time and platelet aggregation density.

  The compositions of the present invention may be useful for any subject, and they are treated for hypertriglyceridemia, hypercholesterolemia, Frederickson dyslipidemia, and other comorbidities. May be particularly useful in certain patient populations, including, but not limited to, subjects that are or in need of treatment. The present invention is provided for a method of treating a subject who has not previously had a cardiovascular event or has previously had one or more treatment cardiovascular events. In some embodiments, subjects treated with or administered a composition of the invention are selected based on their dyslipidemic profile. Subjects can be selected for treatment / administration from the following categories: hypertriglyceridemia (eg, TG ≧ 750 mg / dL, TG ≧ 500 mg / dL, TG ≧ 200 mg / dL, TG ≧ 150 mg / dL, TG500− 2000mg / dL, TG500-1500mg / dL, TG750-2000mg / dL, TG750-1500mg / dL, TG200-499mg / dL, TG300-499mg / dL, TG350-499mg / dL, TG300-750mg / dL, TG300-700mg / dL, TG200-499mg / dL, or TG150-199mg / dL); hypercholesterolemia (eg, LDL-C <70mg / dL, LDL-C ≧ 70mg / dL, LDL-C ≧ 100mg / dL, LDL-C) ≧ 130 / dL, LDL-C ≧ 160 mg / dL, LDL-C ≧ 190 mg / dL, LDL-C 70-100 mg / dL, LDL-C 100-130 mg / dL, LDL-C 130-160 mg / dL, LDL- C 160-190mg / dL, LDL-C 130-190mg / dL, LDL-C 100-160mg / dL, LDL-C 70-130mg / dL, LDL-C 70-160mg / dL, LDL-C 100-190mg / dL, LDL-C 70-190mg / dL, NON-HDL-C <100mg / dL, NON-HDL-C≥100mg / dL, NON-HDL-C≥130mg / dL, NON-HDL-C≥160 / dL , NON-HDL-C ≧ 190mg / dL, NON-HDL-C 100-130mg / dL, NON-HDL-C 130-160mg / dL, NON-HDL-C 160-190mg / dL, NON-HDL-C 130 -190mg / dL, NON-HDL-C 100-160mg / dL Or NON-HDL-C 100-190mg / dL); or Fredrickson dyslipidemia type (I-type, IIa type, IIb, III, IV or V type). In some embodiments, a subject treated with or administered a composition of the invention is selected based on the presence of a particular co-morbidity. Such co-morbidities include, but are not limited to: kidney disease, nephropathy, IgA nephropathy, renal disorder, renal failure (also renal failure (or renal dysfunction), dialysis therapy required Renal dysfunction, renal dysfunction without dialysis, chronic analgesic nephritis, polycystic kidney disease, proteinuria, hypertension, thrombotic microangiopathy, renal failure (acute renal failure, chronic renal failure), Uremic pericarditis, uremia, renal artery stenosis, renal ischemia, hypertensive nephropathy, renovascular hypertension, renal osteodysplasia, nephropathy, renal cortical necrosis, glomerulitis, metabolic syndrome, diabetes In some embodiments, a method of administering a composition of the invention comprises a subject having a cardiac disorder, coronary ischemia, cardiac decompensation, or a diabetic lesion with cardiac disorder, and previously Myocardial infarction, stroke, subacute myocardial infarction Useful in subjects with post-myocardial infarction, acute coronary syndrome (ACS), ACS without ST-segment elevation (NSTEMI), ACS with ST-segment elevation (STEMI), or any other major cardiovascular event is there.

  In some embodiments, treatment with a composition of the invention results in clinical improvement of such comorbidities. In some embodiments, administration with a composition of the invention may reduce the time required to achieve clinical improvement and / or reach a therapeutic goal. In some embodiments, administration of the composition comprises glomerular filtration rate, serum creatinine, serum urea, serum phosphate level, serum potassium level, systolic or diastolic blood pressure, progression to dialysis therapy, renal failure Progression to need for kidney transplant, fasting serum glucose level, postprandial serum glucose level, serum fructosamine level, therapeutic insulin use, progression to diabetes, hypo-glucose events, high It provides clinical improvement in clinical indicators, including but not limited to hyper-glucose events or hemoglobin A1C.

  The compositions of the invention can be co-administered with one or more other therapeutic agents. In some embodiments, the clinical benefit provided by administration or treatment of a composition of the present invention to a subject can be improved when used concurrently or in combination with other therapeutic agents. Examples of such simultaneous treatments or fixed combination treatments may include simultaneous administration in one or more of the following: HMGCoA reductase inhibitors ("statins"), antiplatelet drugs ( For aspirin or clopidogrel), anticoagulants (such as warfarin), antihypertensives (diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor (ARB) antagonists), or heart disease Other treatments.

  The present invention also provides a pharmaceutical composition, eg, a unit dosage form, comprising one or more HMG-CoA reductase inhibitors (“statins”) and the ω3 fatty acid composition of the present invention. In some embodiments, the present invention provides a fixed dose combination product comprising both a statin and a composition of the present invention. The present invention may include currently known or future known statins in amounts generally recognized as safe. Currently, seven statins are widely available: atorvastatin, rosuvastatin, fluvastatin, lovastatin, pravastatin, pitavastatin, and simvastatin. The eighth statin, cerivastatin, has been removed from the US market at the time of writing. However, one skilled in the art will recognize that cerivastatin can be used in combination with some aspects of the present invention if it is determined that cerivastatin is safe and effective in a particular treatment regimen. Such statins are typically used in general daily doses, including lovastatin 10 mg, 20 mg, 40 mg; pravastatin 10 mg, 20 mg, 40 mg, 80 mg; simvastatin 5 mg, 10 mg, 20 mg, 40 mg, 80 mg Fluvastatin 20 mg, 40 mg, 80 mg; atorvastatin 10 mg, 20 mg, 40 mg, 80 mg; rosuvastatin 5 mg, 10 mg, 20 mg, 40 mg; and pitavastatin 1 mg, 2 mg, 4 mg, 8 mg; Usually, the effect of statins is dose-dependent, ie, the higher the dose, the higher the therapeutic effect. However, the effect of each statin is different and therefore the level of therapeutic effect of one statin may not necessarily directly correlate with the level of therapeutic effect of other statins. For example, bioavailability varies greatly between statins. Specifically, simvastatin has been found to have a bioavailability of less than 5%, while fluvastatin has a bioavailability of about 24%. Statins are absorbed at rates ranging from about 30% of lovastatin to 98% of fluvastatin. First pass metabolism occurs in all statins except pravastatin. Pravastatin is also the statin with the lowest protein binding (about 50%) compared to other proteins with protein binding greater than 90%. Statins therefore have different properties from each other. The combination product of the present invention that includes each statin or multiple statins is also unique. The method of treatment combines the administration of one or more statins at a general or alternative dose with the administration of the composition of the present invention.

Example 1
Mixing and homogenizing the intermediates MEGAPEX E90D00EE (90% EPA ethyl ester) and MAXOMEGA DPA95 FFA (≧ 95% DPA synthetic fatty acid produced from EPA ethyl ester concentrate), respectively, converted to ethyl ester in a ratio of 98: 2. By doing so, the composition according to the invention is prepared. These intermediates were prepared and marketed by Chemport Korea (MEGAPEX) and Equateq Ltd (MAXOMEGA), Scotland, UK. The relative amounts of fatty acids present in the starting intermediate and in the resulting new composition are listed in Table 1 below. The resulting new composition was EPA 89.10%, DPA 1.95%, HPA 0.19%, ω3-pentaenoic acid 91.24%, DHA less than 0.01%, ω3-pentaenoic acid 91.24%, total ω3 fatty acid 93.09%, ARA 3.15%, and Contains 3.57% omega-6 fatty acids (all area%).

(Table 1) Fatty acid composition (area%) of intermediates and novel compositions according to Example 1

Example 2
Mixing and homogenizing the intermediates MEGAPEX E90D00EE (90% EPA ethyl ester) and MAXOMEGA DPA95 FFA (≥95% DPA synthetic fatty acids produced from EPA ethyl ester concentrate), respectively, converted to ethyl ester in a 96: 4 ratio By doing so, the composition according to the invention is prepared. These intermediates were prepared and marketed by Chemport Korea (MEGAPEX) and Equateq Ltd (MAXOMEGA), Scotland, UK. The relative amounts of fatty acids present in the starting intermediate and in the resulting new composition are listed in Table 2 below. The resulting new composition contains EPA 87.28%, DPA 3.89%, HPA 0.18%, ω3-pentaenoic acid 91.35%, DHA less than 0.01%, total ω3 fatty acid 93.17%, and ω6 fatty acid 3.49% (all area%) .

(Table 2) Fatty acid composition (area%) of intermediates and novel compositions according to Example 2

Example 3
Mixing and homogenization of intermediates MEGAPEX E90D00EE (90% EPA ethyl ester) and MAXOMEGA DPA95 FFA (≧ 95% DPA synthetic fatty acid produced from EPA ethyl ester concentrate), respectively, converted to ethyl ester in a ratio of 94: 6 By doing so, the composition according to the invention is prepared. These intermediates were prepared and marketed by Chemport Korea (MEGAPEX) and Equateq Ltd (MAXOMEGA), Scotland, UK. The relative amounts of fatty acids present in the starting intermediate and in the resulting new composition are listed in Table 3 below. The resulting new composition is EPA 85.46%, DPA 5.84%, HPA 0.18%, ω3-pentaenoic acid 91.48%, DHA less than 0.01%, total ω3 fatty acid 93.26%, ARA 3.02%, and ω6 fatty acid 3.42% (all areas %)including.

Table 3 Fatty acid composition (area%) of intermediates and novel compositions according to Example 3

Example 4
Mixing and homogenizing the intermediate MEGAPEX E90D00EE (90% EPA ethyl ester) and MAXOMEGA DPA95 FFA (≧ 95% DPA synthetic fatty acid produced from EPA ethyl ester concentrate), respectively, converted to ethyl ester in a ratio of 75:25 By doing so, the composition according to the invention is prepared. These intermediates were prepared and marketed by Chemport Korea (MEGAPEX) and Equateq Ltd (MAXOMEGA), Scotland, UK. The relative amounts of fatty acids present in the starting intermediate and in the resulting new composition are listed in Table 4 below. The resulting new composition is EPA 68.10%, DPA 24.32%, HPA 0.19%, ω3-pentaenoic acid 92.65%, DHA less than 0.01%, total ω3 fatty acid 94.07%, ARA 2.41%, and ω6 fatty acid 2.73% (all areas %)including.

Table 4 Fatty acid composition (area%) of intermediates and novel compositions according to Example 4

Example 5
The composition according to the invention is prepared by mixing and homogenizing the intermediates KD-PharmaKD-PUR 900EE and MAXOMEGA DPA95 FFA, respectively converted to ethyl ester, in a ratio of 60:40. These intermediates were prepared and marketed by KD-Pharma (KD-Pharma) in Germany and Equateq Ltd (MAXOMEGA) in Scotland, UK. The relative amounts of fatty acids present in the starting intermediate and in the resulting new composition are listed in Table 5 below. The resulting new composition comprises EPA 55.74%, DPA 39.26%, HPA 2.39%, ω3-pentaenoic acid 97.44%, and total ω3 fatty acid 98.06% (all area%).

(Table 5) Fatty acid composition (area%) of intermediates and novel compositions according to Example 5

Example 6
The composition according to the invention is prepared by mixing and homogenizing the intermediates KD-PUR 900EE KD-Pharma and MAXOMEGA DPA95 FFA, respectively converted to ethyl ester, in a ratio of 96: 4. These intermediates were prepared and marketed by KD-Pharma (KD-Pharma) in Germany and Equateq Ltd (MAXOMEGA) in Scotland, UK. The relative amounts of fatty acids present in the starting intermediate and in the resulting new composition are listed in Table 6 below. The resulting new composition comprises EPA 89.27%, DPA 4.45%, HPA 3.82%, ω3-pentaenoic acid 97.54%, and total ω3 fatty acid 98.54% (all area%).

Table 6 Fatty acid composition (area%) of intermediates and novel compositions according to Example 6

Example 7
The composition according to the invention is prepared by mixing and homogenizing the intermediate KD-PUR 910EE KD-Pharma and DPA95 FFA, respectively converted to ethyl ester, in a ratio of 91.8: 8.2. The relative amounts of fatty acids present in the starting intermediate and in the resulting new composition are listed in Table 7 below.

Table 7: Fatty acid composition (area%) of intermediate and novel composition according to Example 7

Example 8
The ethyl ester composition of Example 4 can be converted to a free fatty acid composition having essentially the same fatty acid composition according to the following “EE to FFA Conversion Method”. This method is indistinguishable in terms of fatty acid type, saturation, or length when performed in the appropriate amount of time under the conditions described.

How to convert from EE to FFA
1. Put fatty acid ethyl ester (FAEE GMP, approx. 3 mmol / g) oil in a closed heated / cooled reaction chamber (preferably with pressure control) under nitrogen atmosphere and heat to 50-60 ° C. with stirring .
2. Add 2M NaOH aqueous solution with good stirring to ensure phase mixing (estimated 2-3 × FAEE w / w) and stir until no ethyl ester is present (estimated 2-4 hours). The presence of the ethyl ester is tested on laboratory scale / in production by TLC (Hexane / EtOAc 9: 1) and EP GC method to confirm completion of reaction under GMP.
3. Under cooling (maintain the mixture below 70 ° C.), add 6M aqueous HCl until slightly acidic (pH about 3-4) (less than estimated 1 hour). It may be necessary to control the pressure to prevent excessive foaming. Stirring is then stopped and the phases are separated by time and the aqueous phase is removed from the bottom (keeping the oil protected from oxygen and applying a nitrogen blanket).
4. Add demineralized water (estimated 2-3 × FAEE w / w) and wash NaCl and ethanol out of the oil (estimated about 1 hour) with good agitation. Stirring is stopped, the phases are separated by time, and the aqueous phase is removed from the bottom (keeping the oil protected from oxygen and applying a nitrogen blanket).
5. Repeat step 4 several times (about 2 times) to remove ethanol and NaCl.
6. USP residual solvent method by removing water and residual ethanol [determining control of production process] and stirring oil while applying vacuum pressure of 10-50mbar (target value: less than 100ppm ethanol) (using solvent trap) ) Heat the oil until it reaches the water / ethanol target value (70-80 ° C) (estimated 2-4 hours).
7. Add antioxidants (ie α-D-tocopherol, USP, target 4 mg / g) and / or other excipients.
8. All reagents and excipients are USP grade.

Example 9
The ethyl ester composition of Example 3 is converted to a free fatty acid composition having essentially the same fatty acid composition in accordance with the “EE to FFA Conversion Method” described above. This method is indistinguishable in terms of fatty acid type, saturation, or length when performed in the appropriate amount of time under the conditions described.

Example 10
The ethyl ester composition of Example 6 is converted to a free fatty acid composition having essentially the same fatty acid composition in accordance with the “EE to FFA Conversion Method” described above. This method is indistinguishable in terms of fatty acid type, saturation, or length when performed in the appropriate amount of time under the conditions described.

Example 11
The composition of Example 4 is formulated into soft gelatin capsules. Prior to encapsulation, the addition of an antioxidant preparation (composed of 4000 mg α-D-tocopherol in 1 liter of corn oil; corn oil is a low ω3 triglyceride) to the composition of Example 4 was performed This is accomplished by mixing 100 mL of this antioxidant preparation in 100 liters of the oil composition of Example 4, homogenizing and then thoroughly homogenizing. The resulting pre-encapsulated formulated oil contains about 4 mg / gram of α-D-tocopherol. Subsequently, the formulated oil is placed in a soft gelatin capsule with a logo printed according to the general methods normally used for fish oils by Canadian Accucaps, or by any other documented and practical encapsulation method. Encapsulated. The fill weight of the oil is about 1.08 grams / capsule, which provides a dose of about 1000 mg ω3-pentaenoic acid ethyl ester per capsule. Finally, the capsules are bottled into HDPE bottles with induction seals and child resistant caps.

Example 12
The composition of Example 9 is formulated into soft gelatin capsules. Prior to encapsulation, the addition of an antioxidant preparation (composed of 4000 mg α-D-tocopherol in 1 liter of corn oil; corn oil is a low ω3 triglyceride) to the composition of Example 4 was performed This is accomplished by mixing 100 mL of this antioxidant preparation in 100 liters of the oil composition of Example 4, homogenizing and then thoroughly homogenizing. The resulting pre-encapsulated formulated oil contains about 4 mg / gram of α-D-tocopherol. Subsequently, in a soft gelatin capsule with a logo printed, according to the general methods usually used for fish oil by North Point High Point Banner or by any other documented and practical encapsulation method Formulated oil is encapsulated. The oil fill mass is about 1.09 grams / capsule, which provides a dose of about 1000 mg of ω3-pentaenoic acid per capsule. Finally, the capsules are bottled into HDPE bottles with induction seals and child resistant caps.

Example 13
The composition of Example 5 is formulated into soft gelatin capsules. Prior to encapsulation, the addition of an antioxidant preparation (composed of 4000 mg α-D-tocopherol in 1 liter of corn oil; corn oil is a low ω3 triglyceride) to the composition of Example 4 was performed This is accomplished by mixing 100 mL of this antioxidant preparation in 100 liters of the oil composition of Example 4, homogenizing and then thoroughly homogenizing. The resulting pre-encapsulated formulated oil contains about 4 mg / gram of α-D-tocopherol. Subsequently formulated in soft gelatin capsules with logos printed according to the general methods normally used for fish oil by St. Petersburg, Florida, or by any other documented and practical encapsulation method Oil is encapsulated. The fill weight of the oil is about 1.05 grams / capsule, which provides a dose of about 1000 mg ω3-pentaenoic acid ethyl ester per capsule. Finally, the capsules are bottled into HDPE bottles with induction seals and child resistant caps.

Example 14
The composition of Example 10 is formulated into a soft gelatin capsule. Prior to encapsulation, the addition of an antioxidant preparation (composed of 4000 mg α-D-tocopherol in 1 liter of corn oil; corn oil is a low ω3 triglyceride) to the composition of Example 4 was performed This is accomplished by mixing 100 mL of this antioxidant preparation in 100 liters of the oil composition of Example 4, homogenizing and then thoroughly homogenizing. The resulting pre-encapsulated formulated oil contains about 4 mg / gram of α-D-tocopherol. Subsequently, in a soft gelatin capsule with a logo printed, according to the general methods usually used for fish oil by North Point High Point Banner or by any other documented and practical encapsulation method Formulated oil is encapsulated. The fill weight of the oil is 1.06 grams / capsule, which provides a dose of about 1000 mg ω3-pentaenoic acid per capsule. Finally, the capsules are bottled into HDPE bottles with induction seals and child resistant caps.

Example 15
The patient has been diagnosed with vascular disease. The patient can then begin daily treatment with one of the encapsulated compositions according to Examples 10, 11, 12, or 13. Four capsules per day are given to this patient (4 g / day).

Example 16
The patient is treated as in Example 15. Treatment results in a significant reduction in the occurrence of MACE.

Example 17
The following are examples of preferred embodiments of the present invention.

  In compositions 1a and 1b, the EPA: HPA ratio is 13-190, the EPA: DPA ratio is 8-15, the HPA: DPA ratio is 0.05-1 and the DPA: DHA ratio is greater than 2.4, preferably More than 4, more preferably more than 6, most preferably more than 10, and the EPA: DHA ratio is more than 32, preferably more than 38, more preferably more than 80, most preferably more than 95. EPA, HPA, DPA, and DHA can be configured as glycerides (such as triglycerides), esters (such as ethyl esters), or free fatty acids.

Example 18
The following are examples of preferred embodiments of the present invention.

  In composition 2, the EPA: HPA ratio is 0.25-12, the DPA: EPA ratio is 13-63, the DPA: HPA ratio is 13-190, and the DPA: DHA ratio is greater than 32, preferably 38 Greater than 80, more preferably greater than 80, most preferably greater than 95, and the EPA: DHA ratio is greater than 00.6, preferably greater than 1.5, more preferably greater than 2.4, and most preferably greater than 6. EPA, HPA, DPA, and DHA can be configured as glycerides (such as triglycerides), esters (such as ethyl esters), or free fatty acids.

Example 19
The following is an example of embodiments of the present invention.

  DPA may be configured as glycerides (such as triglycerides), esters (such as ethyl esters), or free fatty acids.

Example 20
The following is an example of embodiments of the present invention.

Example 21
Combining 1 g DPA ethyl ester (SE-133-III) with 10 g EPA ethyl ester 914 mg / g (KD Pharma FM13001) in 150 ml 95% ethanol / water containing 35 ml 2M sodium hydroxide A mixture was prepared. The reaction mixture was stirred overnight at ambient temperature. Tlc analysis showed complete conversion of ethyl ester to the corresponding acid. The reaction mixture was cooled in an ice bath, acidified with 6N hydrochloric acid and concentrated under reduced pressure on a rotary evaporator. Water and ethyl acetate were added, the phases were separated and the aqueous residue was extracted with ethyl acetate. The ethyl acetate extracts were combined, dried over sodium sulfate and concentrated to dryness under reduced pressure on a rotary evaporator. Yield: 9.83g. The ethyl ester mixture was then converted to free fatty acids as described in Example 8.

  A representative sample of this ethyl ester composition was analyzed using capillary injection by capillary gas chromatography with a 30 meter x 0.25 mm Restek Stabil wax column using temperature programming.

DESCRIPTION OF EMBODIMENTS OF THE INVENTION
1. Contains at least 50% omega-3 fatty acids, salts or derivatives thereof, but contains eicosapentaenoic acid (EPA; C20: 5-n3) and docosapentaenoic acid (DPA; C22: 5-n3), and EPA: DHA Fatty acid composition with a ratio greater than 20: 1.
2. Contains at least 60% omega-3 fatty acids, salts or derivatives thereof, but contains eicosapentaenoic acid (EPA; C20: 5-n3) and docosapentaenoic acid (DPA; C22: 5-n3), and EPA: DHA Fatty acid composition with a ratio greater than 20: 1.
3. Contains at least 70% omega-3 fatty acids, salts or derivatives thereof, but contains eicosapentaenoic acid (EPA; C20: 5-n3) and docosapentaenoic acid (DPA; C22: 5-n3), and EPA: DHA Fatty acid composition with a ratio greater than 20: 1.
4. Contains at least 75% omega-3 fatty acids, salts or derivatives thereof, but contains eicosapentaenoic acid (EPA; C20: 5-n3) and docosapentaenoic acid (DPA; C22: 5-n3), and EPA: DHA Fatty acid composition with a ratio greater than 20: 1.
5. Contains at least 80% omega-3 fatty acids, salts or derivatives thereof, but contains eicosapentaenoic acid (EPA; C20: 5-n3) and docosapentaenoic acid (DPA; C22: 5-n3), and EPA: DHA Fatty acid composition with a ratio greater than 20: 1.
6. Contains at least 85% omega-3 fatty acids, salts or derivatives thereof, but contains eicosapentaenoic acid (EPA; C20: 5-n3) and docosapentaenoic acid (DPA; C22: 5-n3), and EPA: DHA Fatty acid composition with a ratio greater than 20: 1.
7. Contains at least 90% omega-3 fatty acids, salts or derivatives thereof, but contains eicosapentaenoic acid (EPA; C20: 5-n3) and docosapentaenoic acid (DPA; C22: 5-n3), and EPA: DHA Fatty acid composition with a ratio greater than 20: 1.
8. Contains at least 95% omega-3 fatty acids, salts or derivatives thereof, but contains eicosapentaenoic acid (EPA; C20: 5-n3) and docosapentaenoic acid (DPA; C22: 5-n3), and EPA: DHA Fatty acid composition with a ratio greater than 20: 1.
9. A composition according to one of the preferred embodiments 1 through 8, comprising at least 2% docosapentaenoic acid (DPA; C22: 5-n3).
10. A composition according to one of the preferred embodiments 1 through 8, comprising at least 4% docosapentaenoic acid (DPA; C22: 5-n3).
11. A composition according to one of the preferred embodiments 1 through 8, comprising at least 5% docosapentaenoic acid (DPA; C22: 5-n3).
12. A composition according to one of the preferred embodiments 1 through 8, comprising at least 6% docosapentaenoic acid (DPA; C22: 5-n3).
13. A composition according to one of the preferred embodiments 1 through 8, comprising at least 7% docosapentaenoic acid (DPA; C22: 5-n3).
14. A composition according to one of the preferred embodiments 1 through 8, comprising at least 8% docosapentaenoic acid (DPA; C22: 5-n3).
15. A composition according to one of the preferred embodiments 1 through 8, comprising at least 10% docosapentaenoic acid (DPA; C22: 5-n3).
16. The composition according to one of the preferred embodiments 1 through 8, comprising at least 12% docosapentaenoic acid (DPA; C22: 5-n3).
17. A composition according to one of the preferred embodiments 1 through 8, comprising at least 15% docosapentaenoic acid (DPA; C22: 5-n3).
18. A composition according to one of the preferred embodiments 1 through 17, comprising no more than 95% EPA.
19. A composition according to one of the preferred embodiments 1 through 17, comprising no more than 10% omega 6 fatty acids.
20. A composition according to one of the preferred embodiments 1 through 17, comprising no more than 7% omega 6 fatty acids.
21. A composition according to one of the preferred embodiments 1 through 17, comprising no more than 5% omega 6 fatty acids.
22. A composition according to one of the preferred embodiments 1 through 17, comprising no more than 3% omega 6 fatty acids.
23. A composition according to one of the preferred embodiments 1 through 22, comprising no more than 5% arachidonic acid (C22: 4-n6).
24. A composition according to one of the preferred embodiments 1 through 22, comprising no more than 4% arachidonic acid (C22: 4-n6).
25. A composition according to one of the preferred embodiments 1 through 22, comprising no more than 3% arachidonic acid (C22: 4-n6).
26. A composition according to one of the preferred embodiments 1 through 22, comprising no more than 2% arachidonic acid (C22: 4-n6).
27. A composition according to one of the preferred embodiments 1 through 22, comprising no more than 1% arachidonic acid (C22: 4-n6).
28. The composition according to one of the preferred embodiments 1 through 27, which also comprises heneicosapentaenoic acid (C21: 5-n3).
29. A composition according to one of the preferred embodiments 1 through 27, comprising at least 0.01% heneicosapentaenoic acid (C21: 5-n3).
30. A composition according to one of the preferred embodiments 1 through 27, comprising at least 0.1% heneicosapentaenoic acid (C21: 5-n3).
31. A composition according to one of the preferred embodiments 1 through 27, comprising at least 0.3% heneicosapentaenoic acid (C21: 5-n3).
32. A composition according to one of the preferred embodiments 1 through 27, comprising at least 0.5% heneicosapentaenoic acid (C21: 5-n3).
33. A composition according to one of the preferred embodiments 1 through 27, comprising at least 1% heneicosapentaenoic acid (C21: 5-n3).
34. A composition according to one of the preferred embodiments 1 through 27, comprising at least 2% heneicosapentaenoic acid (C21: 5-n3).
35. A composition according to one of the preferred embodiments 1 through 27, comprising at least 3% heneicosapentaenoic acid (C21: 5-n3).
36. A composition according to one of the preferred embodiments 1 through 27, comprising at least 4% heneicosapentaenoic acid (C21: 5-n3).
37. A composition according to one of the preferred embodiments 1 through 27, comprising at least 5% heneicosapentaenoic acid (C21: 5-n3).
38. A composition according to one of the preferred embodiments 1 through 37, comprising 5% or less ω3 fatty acid that is not ω3 pentaenoic acid.
39. A composition according to one of the preferred embodiments 1 through 37, comprising no more than 4% omega 3 fatty acids that are not omega 3 pentaenoic acids.
40. A composition according to one of the preferred embodiments 1 through 37, comprising 3% or less ω3 fatty acid that is not ω3 pentaenoic acid.
41. A composition according to one of the preferred embodiments 1 through 37, comprising no more than 2% omega 3 fatty acids that are not omega 3 pentaenoic acids.
42. A composition according to one of the preferred embodiments 1 through 37, comprising no more than 1.5% omega 3 fatty acids that are not omega 3 pentaenoic acids.
43. A composition according to one of the preferred embodiments 1 through 37, comprising no more than 1.25% omega 3 fatty acids that are not omega 3 pentaenoic acids.
44. The composition according to one of the preferred embodiments 1 through 37, comprising 1% or less ω3 fatty acid that is not ω3 pentaenoic acid.
45. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 99: 1 and 1:99.
46. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 60: 1 and 1:60.
47. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 50: 1 and 1: 10.
48. The composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 40: 1 and 1: 3.
49. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 40: 1 and 1: 2.
50. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 40: 1 and 1: 1.
51. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 30: 1 and 1: 1.
52. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 20: 1 and 1: 1.
53. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 10: 1 and 1: 1.
54. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 5: 1 and 1: 1.
55. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 10: 1 and 2: 1.
56. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 20: 1 and 2: 1.
57. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 30: 1 and 2: 1.
58. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 40: 1 and 2: 1.
59. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 50: 1 and 2: 1.
60. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 10: 1 and 3: 1.
61. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 20: 1 and 3: 1.
62. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 30: 1 and 3: 1.
63. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 40: 1 and 3: 1.
64. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 50: 1 and 3: 1.
65. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 60: 1 and 3: 1.
66. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 10: 1 and 5: 1.
67. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 20: 1 and 5: 1.
68. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 30: 1 and 5: 1.
69. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 40: 1 and 5: 1.
70. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 50: 1 and 5: 1.
71. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 60: 1 and 5: 1.
72. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 20: 1 and 10: 1.
73. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 30: 1 and 10: 1.
74. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 40: 1 and 10: 1.
75. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 50: 1 and 10: 1.
76. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 60: 1 and 10: 1.
77. A composition according to one of the preferred embodiments 1 through 44, wherein the EPA: DPA ratio is between 100: 1 and 10: 1.
78. A composition according to one of the preferred embodiments 1 through 44, comprising between 55% and 95% EPA.
79. A composition according to one of the preferred embodiments 1 through 44, comprising between 60% and 95% EPA.
80. A composition according to one of the preferred embodiments 1 through 44, comprising between 65% and 95% EPA.
81. A composition according to one of the preferred embodiments 1 through 44, comprising between 70% and 95% EPA.
82. A composition according to one of the preferred embodiments 1 through 44, comprising between 75% and 95% EPA.
83. A composition according to one of the preferred embodiments 1 through 44, comprising between 80% and 95% EPA.
84. A composition according to one of the preferred embodiments 1 through 44, comprising between 85% and 95% EPA.
85. A composition according to one of the preferred embodiments 1 through 44, comprising between 90% and 95% EPA.
86. A composition according to one of the preferred embodiments 1 through 44, comprising between 1% and 3% DPA.
87. A composition according to one of the preferred embodiments 1 through 44, comprising between 1% and 5% DPA.
88. A composition according to one of the preferred embodiments 1 through 44, comprising between 2% and 10% DPA.
89. A composition according to one of the preferred embodiments 1 through 44, comprising between 3% and 20% DPA.
90. A composition according to one of the preferred embodiments 1 through 44, comprising between 3% and 30% DPA.
91. A composition according to one of the preferred embodiments 1 through 44, comprising between 3% and 50% DPA.
92. A composition according to one of the preferred embodiments 1 through 44, comprising between 3% and 75% DPA.
93. A composition according to one of the preferred embodiments 1 through 44, comprising between 3% and 90% DPA.
94. A fatty acid composition according to one of the preferred embodiments 1 through 93, wherein the fatty acid is present as an ethyl ester.
95. The fatty acid composition according to one of the preferred embodiments 1 through 93, wherein the fatty acid is present as a free fatty acid.
96. A fatty acid composition according to one of the preferred embodiments 1 through 93, wherein the fatty acid is present as an ester in the form of a diglyceride.
97. The fatty acid composition according to one of the preferred embodiments 1 through 93, wherein the fatty acid is present as an ester in triglyceride form.
98. The fatty acid composition of one of the preferred embodiments 94 through 97, which also comprises a suitable antioxidant at a concentration sufficient to protect the fatty acid of the composition from oxidation.
99. A pharmaceutically suitable formulation comprising one of the compositions according to preferred embodiments 94-98, wherein the amount of eicosapentaenoic acid and docosapentaenoic acid is present in an amount of 100-10,000 mg.
100. A pharmaceutically suitable formulation or dosage form comprising one of the compositions according to preferred embodiments 94 to 98, wherein the amount of eicosapentaenoic acid and docosapentaenoic acid is present in an amount of 250 to 1,250 mg.
101. A pharmaceutically suitable formulation or dosage form comprising one of the compositions according to preferred embodiments 94-98, wherein the amount of eicosapentaenoic acid and docosapentaenoic acid is present in an amount of 500-1,100 mg.
102. A pharmaceutically suitable formulation or dosage form comprising one of the compositions according to preferred embodiments 94 to 98, wherein the amount of eicosapentaenoic acid and docosapentaenoic acid is present in an amount of 100 to 10,000 mg.
103. A method of administering or treating a formulation or dosage form according to one of the preferred embodiments 94-102 for a subject at a daily dose of 100-10,000 mg.
104. A method of administering or treating a formulation or dosage form according to one of the preferred embodiments 94-102 for a subject at a daily dose of 500-5,000 mg.
105. A method of administering or treating a formulation or dosage form according to one of the preferred embodiments 94-102 to a subject at a daily dose of 1,500-4,100 mg.
106. The method of treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with very high triglycerides (500 mg / dL or greater than 500 mg / dL).
107. The method of treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with high triglycerides (200 mg / dL or greater than 200 mg / dL, but less than 500 mg / dL).
108. Preferred embodiments wherein the subject is a patient who has already been treated with a statin and has subsequently been diagnosed with high triglycerides (200 mg / dL or greater than 200 mg / dL but less than 500 mg / dL) The treatment method according to 103 to 105.
109. Treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 200-499 mg / dL and LDL cholesterol 190 mg / dL or greater than 190 mg / dL Method.
110. Treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 300-700 mg / dL and LDL cholesterol 190 mg / dL or greater than 190 mg / dL Method.
111. Preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 200-499 mg / dL and non-HDL cholesterol 200 mg / dL or greater than 200 mg / dL Treatment method.
112. The preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 300-700 mg / dL and non-HDL cholesterol 200 mg / dL or greater than 200 mg / dL Treatment method.
113. Treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 200-499 mg / dL and LDL cholesterol 160 mg / dL or greater than 160 mg / dL Method.
114. Treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 300-700 mg / dL and LDL cholesterol 160 mg / dL or greater than 160 mg / dL Method.
115. The preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 200-499 mg / dL and non-HDL cholesterol 160 mg / dL or greater than 160 mg / dL Treatment method.
116. The preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 300-700 mg / dL and non-HDL cholesterol 160 mg / dL or greater than 160 mg / dL Treatment method.
117. Treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 200-499 mg / dL and LDL cholesterol 130 mg / dL or greater than 130 mg / dL Method.
118. Treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 300-700 mg / dL and LDL cholesterol 130 mg / dL or greater than 130 mg / dL Method.
119. The preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 200-499 mg / dL and non-HDL cholesterol 130 mg / dL or greater than 130 mg / dL Treatment method.
120. The preferred embodiments 103-105, wherein the subject is a patient diagnosed with mixed dyslipidemia having TG 300-700 mg / dL and non-HDL cholesterol 130 mg / dL or greater than 130 mg / dL. Treatment method.
121. The method of treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed / assessed as having a substantially increased risk of cardiovascular events.
122. The treatment method according to preferred embodiments 103 to 105, wherein the subject is a patient diagnosed with diabetes.
123. The method of treatment according to preferred embodiments 103-105, wherein the subject is a patient diagnosed with pre-diabetes or metabolic syndrome.
124. The method of treatment according to one of the preferred embodiments 103 through 123, wherein the treatment results in a significant reduction in blood, serum, or plasma triglyceride levels.
125. The method according to one of the preferred embodiments 103 through 123, wherein the treatment results in a significant decrease in blood, serum, or plasma triglyceride levels, but does not significantly increase blood, serum, or plasma LDL cholesterol levels. Treatment method.
126. The method of treatment according to one of the preferred embodiments 103-123, wherein the treatment results in a significant reduction in blood, serum, or plasma total cholesterol levels.
127. The method of treatment according to one of the preferred embodiments 103 through 123, wherein the treatment results in a significant reduction in blood, serum, or plasma non-HDL cholesterol levels.
128. The method of treatment according to one of the preferred embodiments 103 through 123, wherein the treatment results in a significant reduction in blood, serum, or plasma LDL cholesterol levels.
129. The method of treatment according to one of the preferred embodiments 103-123, wherein the treatment results in a significant reduction in blood, serum, or plasma VLDL cholesterol levels.
130. One of the preferred embodiments 103 through 123, wherein treatment results in a significant decrease in blood, serum, or plasma VLDL cholesterol levels, but does not significantly increase blood, serum, or plasma LDL cholesterol levels. Treatment method.
131. The method of treatment according to one of the preferred embodiments 103-123, wherein the treatment results in a significant decrease in blood, serum, or plasma apo-B levels.
132. The method of treatment according to one of the preferred embodiments 103 through 123, wherein the treatment results in a significant reduction in blood, serum or plasma apo-C-III levels.
133. A method of treatment according to one of the preferred embodiments 103 through 123, wherein the treatment results in a significant decrease in blood, serum, or plasma LP-PLA2 levels.
134. The method of treatment according to one of the preferred embodiments 103 through 123, wherein the treatment results in a significant reduction in blood, serum, or plasma hs-CRP levels.
135. A method of treatment according to one of the preferred embodiments 103 through 123, wherein the treatment results in a significant increase in blood, serum or plasma HDL cholesterol levels.
136. The method of treatment according to one of the preferred embodiments 103-123, wherein the treatment results in a significant increase in blood, serum, or plasma apo-A levels.
137. The method of treatment according to one of the preferred embodiments 103-123, wherein the treatment results in a significant reduction in the risk of suffering from a particular cardiovascular event.
138. The composition of claim 1, wherein the ratio of EPA to DPA (EPA: DPA) is 15: 1 to 8: 1.
139. An orally administrable composition comprising a fatty acid, wherein at least 50% by weight of the fatty acid comprises ω3-pentaenoic acid, a salt, ester, or derivative thereof, the composition comprising eicosapentaenoic acid (EPA), Contains docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), has a DHA to EPA (DHA: EPA) ratio of less than 1:20, and a DHA to DPA (DHA: DPA) ratio of 2: A composition that is less than 1.

Claims (63)

  A method of treating, preventing and / or reducing and ameliorating symptoms associated with the occurrence of MACE, coronary heart disease, vascular disease, and / or arteriosclerotic disease in a subject in need thereof, comprising a fatty acid Administering to the subject, wherein at least 50% by weight of the fatty acid comprises ω3 fatty acid, a salt, ester, or derivative thereof, wherein the ω3 fatty acid is eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) Wherein the ratio of docosahexaenoic acid DHA to EPA (DHA: EPA) is less than 1:10 and the ratio of DHA to DPA (DHA: DPA) is less than 2: 1.   The subject is atherosclerosis, hypertriglyceridemia, mixed dyslipidemia, hypercholesterolemia, peripheral arterial disease (PAD), subacute myocardial infarction (after myocardial infarction), acute coronary syndrome (ACS), ACS without ST-segment elevation (NSTEMI), ACS with ST-segment elevation (STEMI), heart failure, cardiac arrhythmia, blood clotting related to cardiac arrhythmia, hypertension, coagulation-related disorder, nephropathy, renal disorder, dialysis therapy Suffering from another pathological condition selected from the group consisting of renal dysfunction requiring dialysis, renal dysfunction without dialysis therapy, retinopathy, cognitive impairment, dementia, and metabolic syndrome The method described in 1.   The method of claim 1, wherein the ratio of DHA: EPA is less than 1:20.   2. The method of claim 1, wherein the ratio of DHA: DPA is less than 1: 1.   2. The method of claim 1, wherein the ratio of EPA to DPA (EPA: DPA) is 30: 1 to 1: 1.   The method of claim 1, wherein the ratio of DHA: EPA is less than 1:10.   2. The method of claim 1, wherein the composition comprises DHA in an amount that is less than 5% of the total amount of fatty acids.   The method of claim 1, wherein the composition comprises EPA in an amount of about 80% to about 90% of the total amount of fatty acids.   2. The method of claim 1, wherein the composition comprises DPA in an amount of about 5% to about 15% of the total amount of fatty acids.   2. The method of claim 1, wherein the composition comprises DPA free fatty acid or a salt, ester, or derivative of DPA.   2. The method of claim 1, wherein the composition comprises EPA free fatty acids or EPA salts, esters, or derivatives. A method of treating, preventing, and / or reducing and ameliorating symptoms associated with the occurrence of MACE, coronary heart disease, vascular disease, and / or arteriosclerotic disease in a subject in need thereof, comprising eicosapentaenoic acid ( Administering to the subject a composition comprising EPA) in an amount of about 750 mg / g to about 950 mg / g,
And the composition comprises DHA of 5% or less of the total amount of fatty acids,
And the DHA: DPA ratio is 1: 1 or lower.   The subject is atherosclerosis, hypertriglyceridemia, mixed dyslipidemia, hypercholesterolemia, peripheral arterial disease (PAD), subacute myocardial infarction (after myocardial infarction), acute coronary syndrome (ACS), ACS without ST-segment elevation (NSTEMI), ACS with ST-segment elevation (STEMI), heart failure, cardiac arrhythmia, blood clotting related to cardiac arrhythmia, hypertension, coagulation-related disorder, nephropathy, renal disorder, dialysis therapy Suffering from another pathological condition selected from the group consisting of renal dysfunction requiring dialysis, renal dysfunction without dialysis therapy, retinopathy, cognitive impairment, dementia, and metabolic syndrome The method described in 1. The composition comprises eicosapentaenoic acid (EPA) in an amount of about 800 mg / g to about 900 mg / g;
And the composition comprises DHA of 5% or less of the total amount of fatty acids,
13. The method of claim 12, wherein the DHA: DPA ratio is 1: 1 or less. The composition comprises eicosapentaenoic acid (EPA) in an amount of about 830 mg / g to about 870 mg / g;
And the composition comprises DHA of 5% or less of the total amount of fatty acids,
13. The method of claim 12, wherein the DHA: DPA ratio is 1: 1 or less.   13. The method of claim 12, wherein the composition comprises docosapentaenoic acid (DPA) in an amount from about 60 mg / g to about 120 mg / g.   13. The method of claim 12, wherein the composition comprises docosapentaenoic acid (DPA) in an amount from about 70 mg / g to about 100 mg / g. A method of treating, preventing, and / or reducing and ameliorating symptoms associated with the occurrence of MACE, coronary heart disease, vascular disease, and / or arteriosclerotic disease in a subject in need thereof, comprising:
-Eicosapentaenoic acid (EPA) in an amount of about 70% to about 95% of the total amount of fatty acids, and
-Docosapentaenoic acid (DPA)
Administering to the subject a composition comprising:
The composition comprises 5% or less of docosahexaenoic acid (DHA) of the total amount of fatty acids, and
A method wherein the ratio of DHA: DPA is 1: 1 or below.   The subject is atherosclerosis, hypertriglyceridemia, mixed dyslipidemia, hypercholesterolemia, peripheral arterial disease (PAD), subacute myocardial infarction (after myocardial infarction), acute coronary syndrome (ACS), ACS without ST-segment elevation (NSTEMI), ACS with ST-segment elevation (STEMI), heart failure, cardiac arrhythmia, blood clotting related to cardiac arrhythmia, hypertension, coagulation-related disorder, nephropathy, renal disorder, dialysis therapy Suffering from another pathological condition selected from the group consisting of renal dysfunction requiring dialysis, renal dysfunction without dialysis therapy, retinopathy, cognitive impairment, dementia, and metabolic syndrome The method described in 1.   19. The method of claim 18, wherein the composition comprises eicosapentaenoic acid (EPA) in an amount from about 80% to about 90% of the total amount of fatty acids.   19. The method of claim 18, wherein the composition comprises eicosapentaenoic acid (EPA) in an amount from about 82% to about 88% of the total amount of fatty acids.   19. The method of claim 18, wherein the composition comprises docosapentaenoic acid (DPA) in an amount of about 5% to about 15% of the total amount of fatty acids.   19. The method of claim 18, wherein the composition comprises docosapentaenoic acid (DPA) in an amount from about 6% to about 12% of the total amount of fatty acids.   19. The method of claim 18, wherein the composition comprises EPA free fatty acids or EPA salts, esters, or derivatives. A method of treating, preventing, and / or reducing and ameliorating symptoms associated with the occurrence of MACE, coronary heart disease, vascular disease, and / or arteriosclerotic disease in a subject in need thereof, comprising about 1000 mg to Administering to the subject a composition comprising eicosapentaenoic acid (EPA) at a daily dose of about 5000 mg and further comprising docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA);
The method wherein the composition comprises no more than 5% DHA of the total amount of fatty acids and the DHA: DPA ratio is 1: 1 or below.   The subject is atherosclerosis, hypertriglyceridemia, mixed dyslipidemia, hypercholesterolemia, peripheral arterial disease (PAD), subacute myocardial infarction (after myocardial infarction), acute coronary syndrome (ACS), ACS without ST-segment elevation (NSTEMI), ACS with ST-segment elevation (STEMI), heart failure, cardiac arrhythmia, blood clotting related to cardiac arrhythmia, hypertension, coagulation-related disorder, nephropathy, renal disorder, dialysis therapy 25, also suffering from another pathological condition selected from the group consisting of renal dysfunction requiring dialysis, renal dysfunction without dialysis therapy, retinopathy, cognitive impairment, dementia, and metabolic syndrome The method described in 1.   26. The composition of claim 25, wherein the composition comprises eicosapentaenoic acid (EPA) at a daily dose selected from the group consisting of about 1735 mg to about 1855 mg, about 2520 mg to about 2780 mg, and about 3360 mg to about 3710 mg. Method.   The composition comprises eicosapentaenoic acid (EPA) in a daily dose selected from the group consisting of about 1750 mg to about 1950 mg, about 1800 mg to about 2000 mg, about 2650 mg to about 2950 mg, and about 3500 mg to about 3900 mg. 26. The method of claim 25.   26. The composition of claim 25, wherein the composition comprises eicosapentaenoic acid (EPA) at a daily dose selected from the group consisting of about 1900 mg to about 2100 mg, about 2700 mg to about 3300 mg, and about 3700 mg to about 4300 mg. Method.   26. The method of claim 25, wherein the composition comprises EPA free fatty acids or EPA salts, esters, or derivatives.   2. The method of claim 1, wherein the composition comprises DPA free fatty acid or a salt, ester, or derivative of DPA.   A method of treating, preventing, and / or reducing and ameliorating symptoms associated with the occurrence of MACE, coronary heart disease, vascular disease, and / or arteriosclerotic disease in a subject in need thereof, comprising the composition Administering to a subject, the composition comprising eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA), wherein the amount of EPA and DPA is about 55% by weight or more of the total amount of fatty acids, and A method wherein the ratio of DHA: DPA is 1: 1 or less.   The subject is atherosclerosis, hypertriglyceridemia, mixed dyslipidemia, hypercholesterolemia, peripheral arterial disease (PAD), subacute myocardial infarction (after myocardial infarction), acute coronary syndrome (ACS), ACS without ST-segment elevation (NSTEMI), ACS with ST-segment elevation (STEMI), heart failure, cardiac arrhythmia, blood clotting related to cardiac arrhythmia, hypertension, coagulation-related disorder, nephropathy, renal disorder, dialysis therapy Suffering from another pathological condition selected from the group consisting of renal dysfunction requiring dialysis, renal dysfunction without dialysis therapy, retinopathy, cognitive impairment, dementia, and metabolic syndrome The method described in 1.   35. The method of claim 32, wherein the composition comprises a daily dose of about 120 mg / day to about 150 mg / day.   35. The method of claim 32, wherein the composition comprises a daily dose of about 150 mg / day to about 200 mg / day of DPA.   35. The method of claim 32, wherein the composition comprises a daily dose of about 200 mg / day to about 250 mg / day of DPA.   34. The method of claim 32, wherein the composition comprises a daily dose of about 250 mg / day to about 300 mg / day of DPA.   33. The method of claim 32, wherein the composition comprises a daily dose of about 300 mg / day to about 400 mg / day of DPA.   33. The method of claim 32, wherein the composition comprises a daily dose of about 400 mg / day to about 600 mg / day of DPA.   33. The method of claim 32, wherein the composition comprises a daily dose of about 600 mg / day to about 1000 mg / day of DPA.   The composition further comprises eicosapentaenoic acid (EPA), and the amount of EPA and DPA is about 55% by weight or more of the total amount of fatty acids, and the ratio of DHA: DPA is 1: 1 or less; 33. A method according to claim 32.   The amount of EPA and DPA is about 60% or more of the total amount of fatty acids, about 65% or more, about 70% or more, about 75% or more, about 80% or more 35. The method of claim 32, wherein the method is selected from the group consisting of: about 85% or more, and about 90% or more.   33. The method of claim 32, wherein the composition further comprises ω6 fatty acids in an amount of 6% or less of the total amount of fatty acids.   33. The method of claim 32, wherein the composition comprises docosahexaenoic acid (DHA) of about 30% or less by weight of fatty acids present in the composition.   35. The method of claim 32, wherein the composition comprises docosahexaenoic acid (DHA) of about 10% or less by weight of fatty acids present in the composition.   33. The method of claim 32, wherein the composition comprises docosahexaenoic acid (DHA) of about 5% or less by weight of fatty acids present in the composition.   35. The method of claim 32, wherein the composition comprises DPA in the form of an ethyl ester.   35. The method of claim 32, wherein the composition comprises DPA in the form of free fatty acids.   33. The method of claim 32, wherein the composition further comprises docosahexaenoic acid (DHA) and the ratio of DHA: DPA is 2: 1 or less.   33. The method of claim 32, wherein the composition further comprises docosahexaenoic acid (DHA) and the ratio of DHA: DPA is 1: 1 or less.   35. The method of claim 32, wherein the composition further comprises docosahexaenoic acid (DHA) and the ratio of DHA: DPA is no greater than 1: 2.   33. The method of claim 32, wherein the composition further comprises docosahexaenoic acid (DHA) and the ratio of DHA: DPA is 1: 4 or less.   35. The method of claim 32, wherein the composition comprises docosapentaenoic acid (DPA) at least about 6% by weight of fatty acids present in the composition.   36. The method of claim 32, wherein the composition comprises docosapentaenoic acid (DPA) at least about 20% by weight of fatty acids present in the composition.   33. The method of claim 32, wherein the composition comprises docosapentaenoic acid (DPA) at least about 50% by weight of fatty acids present in the composition.   A method of treating, preventing and / or reducing and ameliorating symptoms associated with the occurrence of MACE, coronary heart disease, vascular disease, and / or arteriosclerotic disease in a subject in need thereof, Docosapentaenoic acid (DPA) in an amount of about 50% to about 80%, Docosahexaenoic acid (DHA) in an amount of about 25% to about 40% of the total amount of fatty acids, and optionally an amount of about 10% of the total amount of fatty acids Administering a composition comprising eicosapentaenoic acid (EPA) to the subject.   The subject is atherosclerosis, hypertriglyceridemia, mixed dyslipidemia, hypercholesterolemia, peripheral arterial disease (PAD), subacute myocardial infarction (after myocardial infarction), acute coronary syndrome (ACS), ACS without ST-segment elevation (NSTEMI), ACS with ST-segment elevation (STEMI), heart failure, cardiac arrhythmia, blood clotting related to cardiac arrhythmia, hypertension, coagulation-related disorder, nephropathy, renal disorder, dialysis therapy 57, also suffering from another pathological condition selected from the group consisting of renal dysfunction requiring dialysis, renal dysfunction without dialysis therapy, retinopathy, cognitive impairment, dementia, and metabolic syndrome The method described in 1.   57. The method of claim 56, wherein the composition comprises docosapentaenoic acid (DPA) in an amount of about 50% to 75% of the total amount of fatty acids.   57. The method of claim 56, wherein the composition comprises docosapentaenoic acid (DPA) in an amount of about 50% to 65% of the total amount of fatty acids.   57. The method of claim 56, wherein the composition comprises docosahexaenoic acid (DHA) in an amount of about 25% to about 35% of the total amount of fatty acids.   57. The method of claim 56, wherein the composition comprises docosahexaenoic acid (DHA) in an amount of about 30% to about 35% of the total amount of fatty acids.   57. The method of claim 56, wherein the composition comprises eicosapentaenoic acid (EPA) in an amount less than about 8% of the total amount of fatty acids.   57. The method of claim 56, wherein the composition comprises eicosapentaenoic acid (EPA) in an amount less than about 5% of the total amount of fatty acids.