Compositions and methods for diagnosis and treatment of inflammation

Abstract

To provide various compositions and methods for the treatment or prophylaxis of inflammation and associated conditions.SOLUTION: The compositions comprise one or more fatty acids, derivatives of fatty acids, or salts thereof. These may be administered in combination with other pharmaceuticals or as part of various therapeutic regimens. The provided compositions are effective in modulating markers associated with chronic inflammation. Various methods are provided for administering the compositions.SELECTED DRAWING: None

Description

[Technical Field]

[0001] [STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT] The United States Government is pleased to announce that Federal Grant No. N00014-15-1-2131 (National Marine Mammal Foundation) ) has proprietary rights in the subject invention pursuant to a transfer of title to the subject invention. Enquiries regarding permission may be made to: :Office of Research and Technical Application ations, Space and Naval Warfare Systems C enter,Pacific,Code 72120,San Diego,CA,92 152;Tel:(619)553-5118;Email:ssc_pac_t2@navy .mil.

[0002] Inflammation and inflammation-related conditions (including cardiometabolic disease, cancer, and various conditions of aging) a composition for the treatment or prevention of a disease, the composition comprising a fatty acid and its salts and derivatives; Treatment of inflammation and inflammation-related conditions, including cardiometabolic disease, cancer, and various conditions of aging Therapeutic or preventative measures for inflammation and various inflammation-related conditions (anemia of chronic disease, inflammation insulin resistance, metabolic syndrome, autoimmune diseases, hypertension, diabetes, non-alcoholic fatty liver disease, cardiovascular disease, cancer, aging, neurodegenerative diseases (Alzheimer's disease and Compositions and methods for treating dementia (including other forms of dementia and other related conditions) The present invention also provides methods and methods for the preparation of such a system. [Background technology]

[0003] Inflammation is caused by the erythrocyte sedimentation rate, C-reactive protein in the blood, cytokines and other markers. High blood sugar and / or low blood alkaline phosphatase Chronic inflammation is indicated by detection of the inflammation over a sustained period of time. may arise from an undiagnosed cause, or may persist for months without an acute cause. Chronic inflammation can lead to obesity, diabetes, metabolic syndrome, cancer, and heart disease. Common causes of various very common diseases, including cardiovascular diseases and various diseases of aging Inflammation has been identified as a causative or contributing factor to these conditions. As such, inflammation is a key component of treatments to prevent, manage, and treat these conditions. It has also been proposed as a therapeutic target for treatment. Summary of the Invention [Means for solving the problem]

[0004] Various compositions and methods are provided for the treatment or prevention of inflammation and associated conditions. These compositions contain one or more fatty acids, fatty acid derivatives, or salts thereof. (However, these may be used in combination with other pharmaceutical agents and as described herein.) (The compositions provided may be administered as part of various treatment regimens.) The composition is effective for modulating markers associated with the disease. It is provided for. Therefore, the first generally applicable aspect (i.e., the In one or more aspects (which may be freely combined with any of the various aspects or embodiments), or a plurality of fatty acids or pharmaceutically acceptable salts thereof (provided that said one or more fatty acids The fatty acids are selected from the group consisting of odd-chain fatty acids and very long even-chain fatty acids, and and an acceptable carrier. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, any one or more The fatty acid is heptadecanoic acid or pentadecanoic acid. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the aspect (which can be freely combined with any of the above), the composition is an even-numbered chain. Substantially free of fatty acids. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, any one or more The fatty acid is behenic acid or lignoceric acid. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the composition comprises at least It contains at least one odd-chain fatty acid and at least one very long even-chain fatty acid. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, any one or more The fatty acids include heptadecanoic acid and behenic acid. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the present invention, the composition is a unit dose It is a pharmaceutical form. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the pharmaceutical composition comprises: 2.5 mg to 11 mg of one or more of the above fatty acids or pharmaceuticals thereof per kg of body weight The pharmaceutical composition is adapted for administration to a patient of a physiologically acceptable salt thereof. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the pharmaceutical composition comprises: It is designed for one administration per day. The first aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the pharmaceutical composition comprises: 0.01 mg to 10,000 mg of one or more of the above fatty acids or a pharmaceutically acceptable salt thereof This includes salts that can be extracted. A second aspect that is generally applicable (i.e., the various aspects identified herein) In an aspect which can be freely combined with any of the above embodiments, inflammation and inflammation-related The method of claim 1, wherein the compound of claim 1 is a compound selected from the group consisting of benzodiazepines, ... In any such embodiment, the use of the pharmaceutical composition of the embodiment, wherein the inflammation-related condition is , anemia of chronic disease, insulin resistance, metabolic syndrome, autoimmune diseases, hypertension blood pressure, diabetes, non-alcoholic fatty liver disease, cardiovascular disease, cancer, aging, neurodegenerative diseases, The use is provided wherein the disease is selected from the group consisting of Alzheimer's disease and dementia. A second aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, which can be freely combined with any of the above, the use is in the manufacture of a medicament for the treatment or prevention of A second aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the pharmaceutical composition comprises: configured to modulate a marker of inflammation or a symptom of inflammation. A second aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the marker of inflammation However, odd-chain fatty acid ratio, serum concentration of odd-chain fatty acids, red blood cell membrane concentration of odd-chain fatty acids, blood Total odd-chain fatty acids in serum, total odd-chain fatty acids in erythrocyte membrane, serum ferritin, erythrocyte sedimentation rate , serum alkaline phosphatase, serum CRP, IL-6, TNFα, c-Jun N-terminus kinase, ATM and monocyte chemotactic protein-1. A second aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the pharmaceutical composition comprises: The serum or erythrocyte membrane concentrations of one or more of the above fatty acids are reduced below the pre-treatment values. At most about 0.001 x 10 -4 It is constructed to increase by M. A third aspect that is generally applicable (i.e., the various aspects identified herein) In an aspect which can be freely combined with any of the above embodiments, inflammation and inflammation-related conditions (anemia of chronic disease, insulin resistance, metabolic syndrome, autoimmune diseases, High blood pressure, diabetes, non-alcoholic fatty liver disease, cardiovascular disease, cancer, aging, neurodegenerative diseases dementia (including Alzheimer's disease and other forms of dementia) and other related conditions A method for treating or preventing a disease comprising administering to a patient in need thereof an effective amount of one of or a plurality of fatty acids or pharmaceutically acceptable salts thereof, Alternatively, the fatty acids may be one or more odd-chain fatty acids, one or more very long even-chain fatty acids, or fatty acids, and combinations thereof. A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, any one or more The fatty acid or a pharmaceutically acceptable salt thereof may be one or more of the fatty acids or in a unit dosage form comprising a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier. It is provided as a pharmaceutical composition. A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the unit dosage form 0.01 mg to 10,000 mg of one or more of the above fatty acids or a pharmaceutically acceptable salt thereof Including acceptable salts. A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, any one or more The odd-chain fatty acids are heptadecanoic acid or pentadecanoic acid. A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the pharmaceutical composition may also Substantially free of short-chain fatty acids. A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, any one or more The very long even-chain fatty acids are behenic acid or lignoceric acid. A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, the pharmaceutical composition comprises a plurality of Contains a variety of fatty acids. A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the present invention, the amount of 2.5 mg to 11 m g of the one or more fatty acids or pharmaceutically acceptable salts thereof is administered to the patient for 1 per kg of body weight per day. A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, any one or more or a pharmaceutically acceptable salt thereof is administered to the patient once per day. . A third aspect (i.e., any of the various aspects or embodiments identified herein) In one embodiment of the above aspect, any one or more serum or erythrocyte membrane concentrations of fatty acids of at least about 0.001 higher than pretreatment values x10 -4 It can be increased by M. A fourth aspect of general applicability (i.e., the various aspects specified herein) In the above aspect, the present invention is essentially the same as the present specification, but can be freely combined with any of the above embodiments. Compositions as described herein are provided. A fifth aspect of general applicability (i.e., the various aspects identified herein) In the above aspect, the present invention is essentially the same as the present specification, but can be freely combined with any of the above embodiments. Compositions as described herein are provided. A sixth aspect of general applicability (i.e., the various aspects specified herein) In the above aspect, the present invention is essentially the same as the present specification, but can be freely combined with any of the above embodiments. The use as described therein is provided. [Brief explanation of the drawings]

[0005] [Figure 1A-B] Figure 1 provides data on reduced erythrocyte sedimentation rate and alkaline phosphatase among individual dolphins while on the modified fish diet. The dotted line in Figure 1A represents study animals in which inflammation (or high erythrocyte sedimentation rate) was reduced while on the modified diet. The dotted line in Figure 1B represents study animals in which inflammation (high alkaline phosphatase) was reduced while on the modified diet.

[0006] [Figure 2A-B] A simple linear regression model was used in dolphins consuming the modified fish diet to provide data on the inverse association between serum concentrations of cholesterol ester C15:0 and phosphatidylcholine C17:0 on erythrocyte sedimentation rate.

[0007] [Figure 3A-B] A simple linear regression model was used in dolphins consuming the modified fish diet to provide data on the inverse association between serum concentrations of hexosylceramide forms of very long even-chain saturated fatty acids (C20:0 and C22:0) with erythrocyte sedimentation rate.

[0008] [Figure 4A-D] Simple linear regression models were used in dolphins consuming the modified fish diet to provide data on the positive association between serum concentrations of cholesterol ester C15:0 and phosphatidylcholine C17:0 with respect to the hexosylceramide forms of very long even-chain saturated fatty acids (C22:0 and C24:0).

[0009] [Figure 5]A flow chart is provided summarizing daily oral doses of odd-chain saturated fatty acids and very-long even-chain saturated fatty acids given to dolphins and the resulting serum fatty acid concentrations achieved that predicted reduced erythrocyte sedimentation rate and reduced inflammation in dolphins consuming the modified fish diet.

[0010] [Figure 6A-C] We provide data on the long-term anti-inflammatory effects of daily oral synthetic C15:0 after 12 weeks of treating high-fat diet-induced obese mice; specifically, the cytokines interleukin-6 (IL-6), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1), also known as chemokine (CC motif) ligand 2 (CCL2), were all reduced compared to vehicle controls. DETAILED DESCRIPTION OF THE INVENTION

[0011] Various inflammation-related and associated conditions (anemia of chronic disease, insulin resistance, metabolic syndrome, syndrome, autoimmune diseases, hypertension, diabetes, non-alcoholic fatty liver disease, cardiac Vascular disease, cancer, aging, neurodegenerative diseases (including Alzheimer's disease and other forms of dementia) and other related conditions) Articles and accompanying methods are provided.

[0012] Chronic inflammation is caused by heightened, prolonged activation of the immune system (elevated pro-inflammatory cytokines). It is an asymptomatic state with various cytokines (including tumor necrosis factor alpha ( TNF-α), interleukin 6 (IL-6), interleukin 1 beta (IL-1 β), interleukin 18 (IL-18) and monocyte chemotactic protein-1 (MCP- 1) as well as other components of chronic inflammation contribute to cardiovascular disease (including atherosclerosis). Systemic inflammation has been identified as an underlying cause or contributing factor to endothelial dysfunction. changes in blood vessel tone and upregulation of coagulation occur, This ultimately leads to atherosclerosis and a wide range of cardiovascular complications. It has been done.

[0013] Chronic inflammation contributes to metabolic syndrome (widespread impairment of energy utilization and storage) Various cytokines (IL-6, IL-1) are recognized as the underlying driving force behind the -1β, IL-18, and MCP-1), as well as other components of chronic inflammation, contribute to metabolic It has been identified as an underlying cause or contributing factor to the syndrome: metabolic syndrome It is estimated that 1 in 4 people worldwide and 1 in 3 people in the United States are affected. The metabolic syndrome includes cardiovascular disease, diabetes (especially type 2 diabetes), and other conditions (e.g., polycystic ovary syndrome, fatty liver disease, nonalcoholic steatohepatitis, cholesterol There is a risk of developing certain conditions, including gallstones, asthma, sleep disorders and some forms of cancer. Diabetic syndrome is characterized by abdominal (central) obesity, elevated blood pressure, elevated insulin, and elevated cholesterol. Fasting plasma glucose, elevated serum triglycerides, and decreased high-density lipoprotein ( HDL levels, a pro-inflammatory state (clinically known as elevated C-reactive protein (CRP)) (recognized by the 'prothrombotic') and characterized by a prethrombotic state.

[0014] Anemia of chronic disease, also known as anemia of inflammation and anemia of inflammation, is a condition caused by a chronic underlying condition. This is anemia associated with the underlying condition (which may be, for example, an infection, inflammation, or cancer). (which may be due to a number of mechanisms that reduce the oxygen-carrying capacity of the circulating RBC population in general) Generally, ACD is mild and may be reduced by mechanisms associated with It develops and appears slowly, with or without any symptoms.

[0015] Inflammation provides a nidus for tumor growth and supports tumor cell survival and migration. It is recognized as an important underlying factor that acts both as a catalyst and a catalyst for cancer. As such, various anti-inflammatory drugs have been proposed as promising treatment options for cancer patients. It is being done.

[0016] Inflammation is a common cause of systemic lupus erythematosus, rheumatoid arthritis, multiple myeloma, multiple sclerosis, and IL-6 is a key component of various autoimmune diseases, including psoriasis. It is known to be involved in the pathogenesis of many autoimmune diseases, including (but not limited to) rheumatoid arthritis. may play an important role in their pathogenesis, As such, various anti-IL-6 molecules have become candidate therapeutic agents for autoimmune diseases. are.

[0017] Aging refers to a series of morphological and functional changes in an organism that occur over time. The term also refers to the decline in biological function after an organism has reached its maximum reproductive potential. Inflammation may contribute to aging through mutations in mitochondrial DNA and other processes. It is believed that various cytokines (IL-6, IL-18 and M CP-1), as well as other components of inflammation, may be the underlying cause or underlying cause of various age-related complications. It has been identified as a contributing factor. By reducing inflammation, it slows down the degenerative processes of aging. This may be the case.

[0018] Subjects suffering from a neurodegenerative condition (e.g., Alzheimer's disease) are those whose dementia is clinically significant. Amyloid beta (a neurodegenerative disease) can cause inflammation long before it is detected by the immune system. It has been reported that the peptides thought to be involved in the proliferation of ATP ultimately cause neuronal damage. This may be correlated with increased inflammation and associated cytokines. cytokines (including IL-6, IL-18, and MCP-1), as well as other components of inflammation. It has been identified as an underlying cause or contributing factor to dementia (including Alzheimer's disease). Reducing amyloid beta may also protect neurons from amyloid beta toxicity, leading to dementia reducing the risk of developing dementia (including Alzheimer's disease) or This may prevent the progression of certain conditions, including Zheimer's disease.

[0019] Including, but not limited to, inflammation and various associated conditions (e.g., cardiovascular disease, insulin resistance) Sex, metabolic syndrome, autoimmune diseases, hypertension, diabetes, anemia of chronic diseases, non- Alcoholic fatty liver disease, cancer, aging, neurodegenerative diseases (Alzheimer's disease and other forms and other related conditions). Protective and risk factors for the condition are assessed in mammalian subjects (e.g., dolphins and humans) In some embodiments of various embodiments, a method for detecting One of the purposes of some embodiments of the various embodiments is to reduce inflammation (which Various conditions can be examined in mammalian subjects (e.g., dolphins and humans), including but not limited to: ) In some implementations of various embodiments, One purpose of the present invention is to provide a method for treating various conditions, including but not limited to inflammation, in mammalian subjects. and to provide a method for detecting the same in, for example, dolphins and humans. one or more fatty acids or fatty acid derivatives (odd-chain fatty acids (e.g., heptadecanoic acid ) and / or certain even-chain fatty acids (e.g., behenic acid, etc.), but are not limited to these. The serum, plasma or erythrocyte membrane levels of the compound (not determined) are measured in mammalian subjects ( It is of interest to provide methods for expanding the phenotype in various mammals (e.g., dolphins and humans). This is one of the objectives of some embodiments of the present invention. One purpose of the present invention is to provide a therapeutic agent for treating certain conditions, including but not limited to inflammation. and providing a fatty acid supplement or prescription fatty acid treatment for preventing or preventing One of the objectives of some embodiments of the various embodiments is to achieve this in a cost-effective manner. The conditions set forth herein, including inflammation, can be easily treated in mammalian subjects (e.g., and to provide methods for detecting and / or treating malaria in animals (e.g., dolphins and humans). And so.

[0020] It is an object of some embodiments of the various embodiments to administer markers of inflammation to mammalian subjects. and to provide a method for regulating the activity of porcine steroids in mammals (e.g., dolphins and humans). It is an object of some embodiments of the various embodiments to treat inflammation in a mammalian subject (e.g., The objective of the present invention is to provide a method for detecting leukemia virus in various animals (e.g., dolphins, dolphins, and humans). It is an object of some embodiments of the present invention to provide a method for treating inflammation in mammalian subjects (e.g., dolphins and The present invention provides methods for treating inflammatory bowel disease in animals and humans. It is an object of some embodiments to provide a method for treating inflammation in mammalian subjects (e.g., dolphins and humans). In some embodiments, the present invention provides a method for preventing the development of inflammatory bowel disease (e.g., rheumatoid arthritis). One of the objectives of the present invention is to provide a method for treating inflammation and associated conditions (anemia of chronic disease, insulin resistance, metastasis, and the like). atherosclerotic syndrome, autoimmune diseases, high blood pressure, diabetes, non-alcoholic fatty liver disease, Various diseases of aging, cardiovascular diseases, cancer, neurodegenerative diseases (Alzheimer's and other forms) conditions referred to herein, including dementia (including dementia of the genitals) and other related conditions and methods for preventing the development of HIV in mammalian subjects (e.g., dolphins and humans). To do this.

[0021] It is an object of some embodiments of the various embodiments to administer odd-chain fatty acids to a mammalian subject. To increase in serum, plasma or red blood cell membranes (e.g., dolphins and humans) One of the objectives of some embodiments of the various embodiments is to provide a method for Increasing long even-chain fatty acids in the serum of mammalian subjects (e.g., dolphins and humans) The object of some embodiments of the present invention is to provide a method for One is for detecting inflammation in mammalian subjects (e.g., dolphins and humans). The present invention provides a method for treating or preventing the development of inflammatory bowel disease. One of the purposes of this formulation is to provide odd-chain fatty acids substantially free of other fatty acids in mammalian subjects. In various embodiments, the invention provides a method for the production of porcine leukemia virus (PLL) in mammals (e.g., dolphins and humans). One object of some embodiments is to provide a method for producing a soluble ... Provided in mammalian subjects (e.g., dolphins and humans) without qualitatively containing That is the thing.

[0022] Detecting and Treating Chronic Inflammation in Mammalian Subjects (e.g., Dolphins and Humans) It is an object of some embodiments of the various embodiments to provide a method for One of the aims of some embodiments of the various embodiments is to provide a method for preparing fatty acids (e.g., odd-chain fatty acids) and administering to mammalian subjects (e.g., dolphins and In some embodiments, the invention provides a method for treating a subject (e.g., a mammal) with a steroid hormone. One object of the present invention is to provide a method for treating inflammation in mammalian subjects, such as dolphins and humans. The object of some embodiments of the present invention is to provide a method for preventing the One of the goals is to investigate the efficacy of inflammatory conditions in mammalian subjects (e.g., dolphins and humans). The present invention provides a method for detecting or treating a cancer. One object of some embodiments is to provide a method for the preparation of behenic acid and / or heptadecanoic acid supplements. The agent is used to treat inflammation in mammalian subjects (e.g., dolphins and humans). The purpose is to provide

[0023] One object of some embodiments of the various embodiments is to provide a method for the preparation of a soluble fatty acid having an odd chain and an extra-long even chain fatty acid. Bioavailable forms of fatty acids are provided to mammalian subjects (e.g., dolphins and humans). One of the aims of some embodiments of the various embodiments is to provide one or more A number of odd-chain fatty acids are administered to a mammalian subject (e.g., One of the aims of some embodiments is to provide However, both odd-chain fatty acids and certain even-chain fatty acids have been reported in mammalian subjects (e.g., dolphins). The present invention provides a method for increasing the activity of IgG in serum of various animals (e.g., humans). One of the aims of some embodiments of the present invention is to provide a method for the detection of mammalian subjects (e.g., dolphins and porpoises) and providing a method for fatty acid elongation in serum, plasma or red blood cell membranes of mice, e.g., mice. One object of some embodiments of the various embodiments is to provide a method for administering a therapeutic agent to a mammalian subject (e.g., Methods for fatty acid chain shortening in serum, plasma or erythrocyte membranes of animals (e.g., dolphins and humans) One of the aims of some embodiments of the various embodiments is to provide a method for Odd-chain fatty acid forms and very long even-chain fatty acid forms (neutral forms (e.g., free fatty acids, cholesterol) esters, diacylglycerides and triacylglycerides), phospholipids (e.g. For example, phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine and lysophosphatidylethanolamine) and sphingolipids (e.g., ceramides) The concentration of hydroxybenzoates (including hydroxybenzoates, hexosylceramides, and sphingosine) in mammalian subjects (e.g., Methods for making changes in serum, plasma or red blood cell membranes of animals (e.g., dolphins and humans) The purpose is to provide

[0024] Compositions and related compounds containing one or more of certain even-chain fatty acids for treating inflammation Related methods are provided, including the step of preparing a composition comprising one or more bioavailable even-chain fatty acids. Provided.

[0025] One or more of the above objectives can be achieved by various compositions, methods, and methods as described herein. and provided or achieved by use.

[0026] [Definition] The term "alcohol" as used herein is a broad term and will be understood by those skilled in the art. The ordinary and customary meaning of each word must be given (and no special meaning or is not limited to any specially defined meaning), and therefore includes, but is not limited to, one or incorporating multiple hydroxy groups, or incorporating multiple hydroxy groups into one or more hydroxy groups or functionalized to contain one or more hydroxy groups. The term "compound" refers to any compound as described herein that is

[0027] The term "derivative" as used herein is a broad term and is understood by those skilled in the art to be must be given its ordinary and customary meaning (and not a special or special meaning) (and is not limited to the meaning otherwise defined), and therefore is not limited to, but may include, one or more Incorporating or substituted by one or more derivative groups or functionalized to include one or more derivative groups. Derivatives include esters, amides, anhydrides, acids, etc. Halides, thioesters, phosphate esters, triphosphate esters and β-sulfenyl These include, but are not limited to, aryl derivatives.

[0028] The term "hydrocarbon" as used herein is a broad term and will be understood by those skilled in the art. All terms and phrases must be given their ordinary and customary meaning (and not just any special meaning or and thus includes, but is not limited to, carbon atoms. Refers to any moiety containing only carbon and hydrogen atoms. Functionalized or substituted The hydrocarbon moiety may be one or more of the groups described elsewhere herein. It has a substituent.

[0029] The term "lipid" as used herein is a broad term and is understood by those skilled in the art. Its ordinary and customary meaning must be given (and no special or special meaning given). (and therefore includes, among other things, but not limited to, Saturated and unsaturated oils and waxes, derivatives, amides, glycerides, fatty acids, fats Alcohols, sterols and sterol derivatives, phospholipids, ceramides, sphingolipids , tocopherols and carotenoids.

[0030] The term "pharmaceutically acceptable" as used herein is a broad term and means Its ordinary and accustomed meaning to those skilled in the art must be given (and no special (and is not limited to a general or specially defined meaning) and therefore However, within the scope of sound medical judgment, excessive toxicity commensurate with a reasonable risk / benefit ratio is not tolerated. with human and animal tissues without irritation, allergic responses or other problem complications and / or suitable for human and animal consumption. The present invention refers to compounds, substances, compositions and / or dosage forms such as:

[0031] The terms "pharmaceutically acceptable salt" and "a pharmaceutically acceptable salt thereof" are used herein. As used herein, it is a broad term and should be construed to have its ordinary and customary meaning to those skilled in the art. It must be given a taste (and not be limited to a special or specially defined meaning). Therefore, it is possible to use, without limitation, pharmaceutically acceptable non-toxic acids or indicates a salt prepared from a base. Suitable pharmaceutically acceptable salts include metal salts, e.g. Aluminum salts, zinc salts, alkali metal salts (e.g., lithium salts, sodium salts and and potassium salts), alkaline earth metal salts (e.g., calcium and magnesium salts etc.); organic salts, for example, lysine, N,N'-dibenzylethylenediamine, chloro Procaine, choline, diethanolamine, ethylenediamine, meglumine (N-methyl glucamine), procaine and tris salts; free acid and free base salts; inorganic salts, e.g. For example, sulfates, hydrochlorides and hydrobromides; and salts currently widely used in medicine. Other salts that are available from various sources well known to those skilled in the art (e.g., The Merck Group, Other salts that are non-toxic and desirable include those listed in the Chemical Index. Any suitable component is acceptable as long as it does not substantially interfere with the activity of the compound described herein. In addition to salts, compounds of the present invention may be selected to form salts of the therapeutic agents discussed above. Pharmaceutically acceptable precursors and derivatives of the compounds can be used. The resulting amides, lower alkyl derivatives and protected derivatives are also included in the preferred embodiment. The compounds of the preferred embodiments may be suitable for use in pharmaceutical compositions and methods. Although it may be possible to administer the compound in the form of a physiologically acceptable salt, it is generally preferred to administer the compound in the form of a physiologically acceptable salt. It is preferred to administer the compound in neutral form.

[0032] The term "pharmaceutical composition" as used herein is a broad term and will be understood by those skilled in the art. The ordinary and customary meaning of each word must be given (and no special meaning or (The term "common" is not limited to its specifically defined meaning) and therefore, without limitation, One or more compounds disclosed herein and other chemical components (e.g., diluents or A pharmaceutical composition refers to a mixture of a compound with a carrier or the like. A pharmaceutical composition is a compound that is easily administered to an organism. Pharmaceutical compositions can also be prepared by reacting a compound with an inorganic or organic acid or base. Pharmaceutical compositions are generally formulated to suit the specific intended route of administration. will be produced.

[0033] As used herein, the term "carrier" is used in the broad sense. and should be given its ordinary and accustomed meaning to those skilled in the art. (and is not limited to any special or specifically defined meaning), and therefore These include, but are not limited to, compounds that facilitate the uptake of compounds into cells or tissues. For example, but not limited to, dimethyl sulfoxide (DMSO) is a Commonly used carriers that facilitate the uptake of the compound into the cells or tissues of a subject. Water, saline solution, ethanol, and mineral oil are also useful in certain pharmaceutical compositions. It is a carrier used in

[0034] As used herein, the term "diluent" as used herein is used in a broad sense. terms and should be given their ordinary and accustomed meaning to those skilled in the art ( and is not limited to any special or specially defined meaning), and therefore including but not limited to, ingredients in pharmaceutical compositions that lack pharmacological activity but are useful in the manufacture of Indicates ingredients that may be pharmaceutically necessary or pharmaceutically desirable, for example: Diluents increase the bulk of potent drugs whose mass is too small for manufacturing and / or administration Diluents may also be used to deliver drugs by injection, ingestion, or inhalation. It may be a liquid for dissolving a drug for administration. A common form of diluent is a buffered aqueous solution that mimics the composition of human blood (e.g., limited (e.g., phosphate buffered saline, but not phosphate buffered saline).

[0035] As used herein, the term "excipient" as used herein is used in a broad sense. terms and should be given their ordinary and accustomed meaning to those skilled in the art ( and is not limited to any special or specially defined meaning), and therefore , including but not limited to bulk, consistency, stability, binding ability, lubrication, disintegration ability, etc. "Diluent" refers to a substance added to a pharmaceutical composition to provide the composition with a therapeutic effect (not present in the composition). It is an excipient.

[0036] As used herein, the term "subject" is used in the broad sense. terms and should be given their ordinary and accustomed meaning to those skilled in the art ( and is not limited to any special or specially defined meaning), and therefore "Animal" refers to, but is not limited to, an animal that has been the object of treatment, observation, or experiment. Includes vertebrates and warm-blooded vertebrates as well as invertebrates, e.g., fish, crustaceans, reptiles "Mammals" include, but are not limited to, Dolphins, mice, rats, rabbits, guinea pigs, dogs, cats, sheep, goats, cows, and horses , primates (e.g., monkeys, chimpanzees, and apes), and specifically humans In some embodiments, the subject is a human.

[0037] As used herein, the terms "treat", "treatment", "therapeutic" or "therapeutic" refer to The term "treatment" is a broad term and should be construed as having its ordinary and accustomed meaning to those skilled in the art. must be given (and limited to a special or specially defined meaning) (and thus, without limitation, the complete cure or elimination of a disease or condition) does not necessarily mean any unwanted marker, sign or symptom of a disease or condition. Any palliative, whatever the degree, should be considered treatment and / or therapy. Furthermore, the procedure may worsen the patient's overall well-being or appearance. It may include acts that are not

[0038] The terms "therapeutically effective amount" and "effective amount" as used herein mean It is a broad term and should be given its ordinary and accustomed meaning to those skilled in the art. (and is not limited to any special or specifically defined meaning) Thus, the active ingredient may be, but is not limited to, an active ingredient that elicits the indicated biological or medical response. For example, a therapeutically effective amount of a compound is a to prevent, alleviate, or reduce the markers or symptoms of a condition in a subject or ameliorate the condition or prolong the survival of the subject being treated. This response can be produced in a tissue, system, animal, or human. The response includes alleviation of the signs or symptoms of the disease being treated. Determination of an effective amount is well within the capabilities of those skilled in the art given the disclosure provided herein. The therapeutically effective amount of the compounds disclosed herein required as a dose is within the range , route of administration, type of animal (including humans) being treated, and the specific animal under consideration. The dosage will depend on the individual's physical characteristics. Dosage may be adjusted to achieve the desired effect. However, factors such as weight, diet, concomitant medication and other factors that one skilled in the medical arts would recognize may also be considered. The results will depend on a variety of factors such as the amount of time the blood is taken to pass through the bloodstream and other factors.

[0039] The term "solvent" as used herein is a broad term and will be understood by those skilled in the art. Its ordinary and customary meaning must be given (and no special or special meaning given). and therefore includes, but is not limited to, other compounds. or a compound having some property of solvent power for the means, polar or non-polar They can be linear or branched, cyclic or aliphatic, aromatic, or naphthenic. and, inter alia, alcohols, derivatives, diesters, ketones, acetates, tert-butyl esters, pens, sulfoxides, glycols, paraffins, hydrocarbons, anhydrides, heterocyclic compounds ( The compounds shown include, but are not limited to:

[0040] Any percentages, ratios or other amounts set forth herein, unless otherwise indicated, It is based on weight.

[0041] [Odd chain fatty acids and very long even chain fatty acids] Fatty acids include saturated and unsaturated fatty acids. The various fatty acids are designated and described using conventional nomenclature as used by those skilled in the art. Saturated fatty acids do not contain carbon-carbon double bonds. Unsaturated fatty acids contain at least Contains one carbon-carbon double bond. Monounsaturated fatty acids contain only one carbon-carbon double bond. Polyunsaturated fatty acids contain two or more carbon-carbon double bonds. The double bond is generally in the cis configuration; however, trans double bonds are also possible. The position of the double bond can be indicated by Δn, where n is the number of double bonds. The carbon atom with the smaller number in each pair of carbon atoms is indicated. Total carbon number: number of double bonds, Δ 二重結合位置 A convenient notation of the form 20:4Δ can be used. For example, 5, 8,11,14 has 20 carbon atoms and four double bonds, the double bonds being at the 5-position carbon. Between the elementary atom and the 6th carbon atom, between the 8th carbon atom and the 9th carbon atom, and between the 11th carbon atom and the 1st carbon atom Fatty acids located between the 2nd carbon atom and between the 14th and 15th carbon atoms (where carbon atom 1 is the carbon of the carboxylic acid group). Oleic acid (cis-Δ9-octadecenoic acid) is a saturated fatty acid. It is a fatty acid, linolenic acid (all-cis-Δ9,12,15-octadecatrienoic acid ) is a polyunsaturated fatty acid. A "C" can be placed before the total number of carbon atoms, and the double bond The position of the bond may not be specified, for example, C20:4 means 20 carbon atoms and 4 represents a fatty acid having a double bond.

[0042] Fatty acids may be referred to by various names: for example, heptadecanoic acid is Decylic acid, margaric acid and n-heptadecylic acid, or when shown as C17:0 In some cases, fatty acids are designated by lipid numbers as known in the art. There is a match.

[0043] In some embodiments, the fatty acid is an odd-chain fatty acid or a very long even-chain fatty acid. In a further embodiment, the one or more fatty acids may be at least It may contain one odd-chain fatty acid or at least one very long even-chain fatty acid.

[0044] Examples of odd-chain fatty acids are margaric acid (heptadecanoic acid, C17:0), pelargonic acid ( Nonanoic acid (C9:0), undecanoic acid (C11:0), nonadecanoic acid (C19:0), Arachidonic acid ((5Z,8Z,11Z,14Z)-eicosapentaenoic acid (C15:0), -5,8,11,14-tetraenoic acid, adrenic acid (all-cis-7,10,13 ,16-docosatetraenoic acid) and osbond acid (all -cis-4,7,10,13,16-docosapentaenoic acid). Or multiple odd-chain fatty acids, from 9 carbon atoms to 31 carbon atoms (9, 11, 13 pcs, 15pcs, 17pcs, 19pcs, 21pcs, 23pcs, 25pcs, 27pcs, 29pcs or 31pcs carbon atoms), for example, 15 to 21 carbon atoms, for example, 17 carbon atoms However, in certain embodiments, a larger odd number or A smaller odd number of carbon atoms may be acceptable. Generally, the one or more odd numbered chains The fatty acids are saturated; however, in certain embodiments, they are monounsaturated or Polyunsaturated odd-chain fatty acids may be acceptable.

[0045] Odd-chain fatty acids may contain saturated or unsaturated hydrocarbon chains. Odd-chain fatty acids may exist as carboxyl derivatives. Odd-chain fatty acids may exist as salts. For example, it may exist as a salt at the carboxyl group. In some cases, one odd-chain fatty acid is present, and in other cases, two odd-chain fatty acids are present. There may be three odd-chain fatty acids, or more odd-chain fatty acids. In some embodiments, a mixture comprising a plurality of odd-chain fatty acids may be present. The odd-chain fatty acids in or may be distinguished by other structural features.

[0046] Odd-chain fatty acids are found in trace amounts in some dairy products, including butter, and It is a component of fish that are rich in fatty acids (e.g., Mansson HL (2008), Fatty acid ids in bovine milk fat, Food Nutr.Res., 52 :4;Luzia LA, Sampaio GR, Castellucci CMN, T orres EAFS(2013), The influence of season on the lipid profiles of five commercia lly important species of Brazilian fish, (See Food Chem., 83:93-97.) Various studies have shown that odd-chain fats Increasing the daily dietary intake of foods containing acid can increase serum or plasma levels of It has been shown that levels can be successfully increased (e.g., Benatar JR. ., Stewart RAH (2014), The effects of ch. aging dairy intake on trans and saturat ed fatty acid levels - results from a ra ndomized controlled study, Nutr.J., 13:32 (See reference).

[0047] As used herein, the term refers to fatty acids (e.g., even-chain fatty acids, etc.). The term "ultra-long" refers to such fatty acids having at least 20 carbon atoms. , for example, fatty acids having 20 to 26 carbon atoms, such as behenic acid (C22:0) Shows.

[0048] The one or more very long even-chain fatty acids may be, for example, 20, 22, 24, 26, or , 28 or 30 carbon atoms; however, in certain embodiments In the form, a larger or smaller even number of carbon atoms is acceptable. Generally, the one or more very long even-chain fatty acids are saturated; however, In certain embodiments, monounsaturated or polyunsaturated very long even-chain fatty acids are acceptable. It may be possible. Very long even-chain fatty acids may exist as carboxyl derivatives. Long even-chain fatty acids may exist as salts, e.g., as salts at the carboxyl group. In some embodiments, one very long even-chain fatty acid may be present, and two There may be one very long even-chain fatty acid, and there may be three very long even-chain fatty acids. There may be very long even-chain fatty acids present, or even longer.

[0049] In some embodiments, the very long even-chain fatty acids in the mixture include a plurality of very long even-chain fatty acids. Chain fatty acids are classified by the amount of unsaturation, the length of the hydrocarbon chain, various degrees of derivatization, or other Very long even-chain fatty acids are sometimes distinguished by their structural features. May be provided.

[0050] Very long even-chain fatty acids are found in pracaxi oil (which is (obtained from the seeds of the Pentaclethra macroloba tree) and benzyl oil (obtained from the seeds of Moringa oleifera) Pure or purified very long even-chain fatty acids are found in trace amounts in It can exist in a variety of physical states. For example, behenic acid is a white It exists as a cream-colored powder or crystals. Behenic acid is used for research purposes in small amounts. It is available in suitable form from several commercial suppliers (e.g., Sigma-Aldrich Corp. Other very long even-chain fatty acids or The salts or derivatives may exist as oils, solids, or crystalline solids.

[0051] Generally, fatty acids (e.g., odd-chain or very long even-chain fatty acids) are either free fatty acids or or derivatives thereof. Such derivatives include acylglycerides Acylglycerides include, but are not limited to, up to three acyl fatty acid esters. Therefore, acylglycerides may be substituted with monoacylglycerols. glycerides (MAG), diacylglycerides (DAG) or triacylglycerides (TAG) The glyceride can include two or more fatty acid esters. For example, the glycerides can include heptadecanoic acid esters and docosanoic acid esters. Glycerides can also be used as structured triacylglycerides (STAGs), plasmalogens, or The fatty acid ester can be at the sn1 or sn2 position or a phospholipid. It is possible for the sn1 and sn2 positions to be at the same lipid The esters may be substituted with different fatty acid esters. As an example, structured triacylglycerides include sn-1,3-C17-sn-2-oleo Oil can be mentioned.

[0052] In some embodiments, the fatty acids are selected from the group consisting of free fatty acids, cholesterol esters, glycolic acid esters, and the like. Cellulose esters (which include monoacylglycerides (MAG), diacylglycerides ( DAG) or triacylglycerol (TAG) , phospholipids (including phosphatidylcholine, lysophosphatidylcholine, phosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylethanolamine or phosphatidylserine Ceramides (including, but not limited to, hexosylceramide) The soluble fiber may be provided as a lipid, such as, but not limited to, a lipid such as a soluble fiber (e.g., a lipid-rich fiber), or a sphingolipid. A non-limiting example of a phosphatidylcholine is 2,3-di-C17:0-phosphatidylcholine. A non-limiting example of a lysophophatidylcholine is 2-lyso-3-di-C17:0 In some embodiments, the fatty acid derivative is β-s-phosphatidylcholine. It can be a β-sulfenyl derivative (e.g., an acid or It is thought that certain compounds (e.g., esters) may be resistant to β-oxidation in the body. As an example, the β-sulfenyl derivative of heptadecanoic acid is converted to tetradecylthioacetate. Various derivatives can be synthesized by a variety of standard methods known to those skilled in the art. This can be done.

[0053] In some embodiments, fatty acids are used in combination with certain types of lipids (e.g., ceramides, lipids, etc.). as a component of lipids (phospholipids, sphingolipids, membrane lipids, glycolipids or triglycerides) This may be the case.

[0054] In some embodiments, the fatty acid (e.g., very long even-chain fatty acid, etc.) is bioavailable. The term "bioavailability" refers to the percentage of an administered dose that is bioavailable. It indicates the proportion of unchanged drug that reaches the systemic circulation and is one of the major pharmacokinetic properties of a drug. By definition, when a drug is administered intravenously, its bioavailability is 100%. As used herein, the term "bioavailable" refers to a compound that is available for administration by methods other than intravenous (e.g., The form of the fatty acid that is successfully absorbed by the body when used in a therapeutically effective amount (e.g., oral). In some embodiments, the very long even-chain fatty acid based composition provides optimal absorption. In some embodiments, the very long even-chain fatty acid has the structure In a further embodiment, the fat may be provided as a hydroxylated triacylglyceride. The acid is present at the sn-2 position of the structured triacylglyceride.

[0055] Pure or purified fatty acids may exist in a variety of physical states. For example: For example, heptadecanoic acid exists as an off-white powder that is stable at room temperature; , in a form suitable for research purposes in small quantities, from several commercial suppliers (e.g., Sigma). -Aldrich Corp., St. Louis, MO). Other fatty acids or their salts or derivatives may be present as oils, solids, crystalline solids or gases. There may be.

[0056] Odd-chain fatty acids or very long even-chain fatty acids or pharmaceutically acceptable salts thereof or derivatives are at least about 10%, at least about 20%, at least about 30%, at least at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least at least about 80%, at least about 90%, at least about 95%, at least about 98%, at least at least about 99%, at least about 99.9%, at least about 99.99% purity, or substantially The fatty acid may be in a highly purified form (e.g., in bulk form or in a pharmaceutically acceptable form thereof). It may be provided in a pure form (percentage of a salt or derivative thereof), provided that substantially pure Impurities at levels such that, without limitation, physiological effects from the presence of the impurities are undetectable. Mixtures of fatty acids, e.g., odd-chain fatty acids and / or or a mixture of very long even-chain fatty acids or pharmaceutically acceptable salts or derivatives thereof. For example, at least about 10%, at least about 20%, at least about 30%, at least about 4 0%, at least about 50%, at least about 60%, at least about 70%, at least about 8 0%, at least about 90%, at least about 95%, at least about 98%, at least about 9 9%, at least about 99.9%, at least about 99.99% pure, or substantially pure The fatty acids or mixtures thereof, or pharmaceutically acceptable salts thereof, may be present in any purity. The resulting salts or derivatives may not contain other fatty acids or fatty acid derivatives, and may contain triglycerides. It may be free of cerides or may be free of phospholipids. As provided herein, odd-chain fatty acids may be used in combination with even-chain fatty acids, either singly or in groups. Even-chain fatty acids include, for example, myristic acid (C14:0 ), palmitic acid (C16:0) or stearic acid (C18:0). In some embodiments, the odd-chain fatty acids as provided herein are short-chain fatty acids (S CFA), medium-chain fatty acids (MCFA), long-chain fatty acids (LCFA) or very long-chain fatty acids (VL May be substantially free of CFA.

[0057] Fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) or pharmaceutically acceptable salts thereof The salts or derivatives that can be obtained may be from any source. In embodiments, the fatty acid or a pharmaceutically acceptable salt or derivative thereof is naturally occurring. They may be present in natural sources, may be isolated from natural sources, and may be semi-synthetic. It may be synthetic, or may be a mixture of one or more of these. The fatty acid or its pharmaceutically acceptable salt or derivative may be produced in the laboratory. may be produced naturally or by enzymatic processes They can be produced by wild-caught microorganisms and by genetically modified microorganisms. may be produced in the wild, may be isolated from animal tissues, or may be produced by chemical synthesis. It may be manufactured by more than one of these processes.

[0058] The fatty acids may be obtained from natural sources (e.g., fish oil) or may be prepared by the process of this technology. It can be synthesized by a variety of methods known in the art. In embodiments, the fatty acids include those present in natural products that are not purified or refined. In such a situation, the undesired components may be present in the product. The removal of components or the concentration of desired components can be achieved using known separation or purification techniques. It may be considered desirable to increase the

[0059] In any compound described, all tautomeric forms are also It is intended to include, without limitation, all tautomers of the carboxyl group. is intended to be encompassed.

[0060] Any compound can give rise to one geometric isomer that can be defined as E or Z. In compounds described herein having multiple double bonds, each double bond The double bonds may independently be E or Z or a mixture thereof.

[0061] If the compounds disclosed herein have unsatisfied valences, the valences are not satisfied by water. hydrogen or its isotopes (e.g., hydrogen-1 (protium) and hydrogen-2 (deuterium)) shall be met.

[0062] Fatty acids as described herein (e.g., odd-chain fatty acids or very long even-chain fatty acids) ) can exist in various crystalline forms (also known as polymorphs, in this case Polymorphs include various crystal packing arrangements of the same elemental composition of a compound), amorphous phases, salts, Solvates and hydrates are included. In some embodiments, the compounds described herein may be The compounds may be solvated with pharmaceutically acceptable solvents such as water or ethanol. In other embodiments, the compounds described herein exist in the unsolvated form Solvates contain either stoichiometric or non-stoichiometric amounts of solvent, and are The process of crystallization using a commercially acceptable solvent (e.g., water or ethanol) Hydrates may form when the solvent is water or when the Alcoholates are formed when the solvent is an alcohol. The compounds can exist in unsolvated as well as solvated forms. The solvated forms are considered unsolvated forms for the purposes of the compounds and methods provided herein. are considered equivalent.

[0063] The compounds described herein can be isotopically labeled. Therefore, substitution with isotopes (e.g., deuterium) may have certain advantages resulting from greater metabolic stability. a particular therapeutic advantage (e.g., increased in vivo half-life or reduced dosage requirements) Isotopic substitutions can be used, for example, to trace the fate of atoms in a compound. By providing an opportunity to monitor the subject's response to the administration of the compound, It may be useful to determine the chemical structure of each chemical element as it appears in the compound structure. may include any isotope of said element. For example, In some cases, hydrogen atoms are explicitly disclosed or understood to be present in the compound. In any position of the compound where a hydrogen atom can be present, the hydrogen atom including, but not limited to, hydrogen-1 (protium) and hydrogen-2 (deuterium), Any isotope of hydrogen is possible. Reference to includes all possible isotopic forms unless the context clearly indicates otherwise.

[0064] The high dietary abundance of various fatty acids was associated with metabolic syndrome in subjects. (e.g., Forouhi N, Koulman A, Sh arp S, Imamura F, Kroger J, Schulze M, et al. (2014) ), Differences in the prospective associa tion between individual plasma phospholi pid saturated fatty acids and incident t ype 2 diabetes:the EPIC-InterAct case-co hort study, Lancet Diabetes Endocrinol., 2 In fact, whole-fat milk consumption is associated with metabolic syndrome markers. has been associated with decreased risk (e.g., Kratz M, Marcovina S, Nelson JE, Yeh MM, Kowdley KV, Callahan H. S et al. (2014), Dairy fat intake is associated with glucose tolerance,hepatic and syste mic insulin sensitivity,and liver fat bu t not beta-cell function in humans, Am.J. See Clin. Nutr., 99:1385-96).

[0065] The mechanism(s) by which fatty acids(s) have beneficial effects is / are not well understood. Without wishing to be limited by theory, it is believed that fatty acids or their derivatives undergo elongation (increase in chain length) or chain shortening by various metabolic processes within the It is believed that fatty acids or their derivatives can be formed. This can result in products that have signaling properties in the body. The fatty acids are signals that substantially contribute to one or more of the conditions set forth herein. In some embodiments, odd-chain fatty acids may be used to produce hydroxylase-linked products. are elongated to form very long chain fatty acids (e.g., very long even chain fatty acids). In some embodiments, very long even-chain fatty acids can be chain shortened to odd-chain fatty acids. Levels of very long even-chain fatty acids are increased after administration of one or more odd-chain fatty acids The level of odd-chain fatty acids in the body may be higher than that of one or more very long even-chain fatty acids. may increase after administration of

[0066] Pharmaceutical compositions containing one or more fatty acids Fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) or salts or derivatives thereof Formulations are provided that include a conductor and at least one excipient. It is generally preferred to administer the compound in an oral formulation; however, other routes of administration are also contemplated. It is illustrated.

[0067] The pharmaceutical compositions described herein can be administered to a subject alone, or alternatively, In compositions mixed with other active agents, such as in combination therapy, or as a carrier The compound may be administered in a composition mixed with a diluent, excipient, or combination thereof. The formulation depends on the route of administration chosen. and various techniques for administration are known to those skilled in the art (see, e.g., "Reming n:The Science and Practice of Pharmacy”, Lippincott Williams & Wilkins, 20th edition (June 2003) 1), and "Remington's Pharmaceutical Sciences ences,” Mack Pub. Co., 18th and 19th eds. (December 1985) and June 1990, respectively).

[0068] The pharmaceutical compositions disclosed herein can be prepared by processes known per se, e.g. For example, mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, enclosing, tabletting or extracting. The pharmaceutical compositions disclosed herein may be prepared by conventional processes. Many of the compounds used in the present invention are provided as salts with pharmaceutically acceptable counterions. This may be the case.

[0069] Numerous techniques for administering compounds exist in the art, including oral delivery. , rectal delivery, topical delivery, aerosol delivery, injection delivery and parenteral delivery (intramuscular injection, skin delivery) subcutaneous injection, intravenous injection, intramedullary injection, intrathecal injection, direct intraventricular injection, intraperitoneal injection, In the present specification, the term "injection" refers to a method of administering a drug to a subject, including, but not limited to, intranasal injection and intraocular injection. any combination of the above methods or other methods as would be known to one skilled in the art (e.g., "Remington: The Science and Pr actice of Pharmacy”, Lippincott Williams& Wilkins, 20th edition (June 1, 2003), and "Remington' s Pharmaceutical Sciences”, Mack Pub.Co., See the 18th and 19th editions (December 1985 and June 1990, respectively) thing).

[0070] In practice, fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) or salts thereof or derivatives are effective when thoroughly mixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may be combined as an ingredient in the desired preparation for administration. The present invention can take a wide variety of forms depending on the nature of the compound. The pharmaceutical compositions are suitable for oral administration in discrete units, each containing a predetermined amount of the active ingredient. provided as individual units (e.g., capsules, cachets, or tablets) containing Furthermore, the composition can be formulated as an oil, a powder, a granule, a solution, or the like. as a suspension in an aqueous liquid; as an oil-in-water emulsion in a non-aqueous liquid; It can be provided as a liquid emulsion or as a water-in-oil type emulsion. In addition to the common dosage forms provided herein, the compounds provided herein or their pharmaceutically acceptable salts may also be administered in the form of oral or topical preparations. Acceptable salts or derivatives may also be administered by controlled release means and / or delivery devices. The compositions can be prepared by any of the various methods of pharmacy. Generally, such methods involve combining the active ingredient with one or more other necessary ingredients. Generally, the compositions comprise an active ingredient in a liquid carrier or finely divided carrier. prepared by uniformly and intimately mixing with a finely divided solid carrier or both. The product can then be conveniently shaped into the desired presentation.

[0071] The formulations can also be administered in a local, rather than systemic, manner, e.g. For example, the compound is injected directly into the infected area, often in a depot or sustained-release formulation. Furthermore, targeted drug delivery systems can be For example, it may be used in liposomes coated with tissue-specific antibodies. do not have.

[0072] The pharmaceutical composition may comprise a fatty acid (e.g., an odd-chain fatty acid or a very long even-chain fatty acid) or its derivatives. The composition may contain a salt or derivative thereof in an amount effective for the desired therapeutic effect. In some embodiments, the pharmaceutical composition is in a unit dosage form, and each unit dosage form contains Including from about 0.1 mg or less to about 5000 mg or more. In embodiments, the pharmaceutical composition is from about 1 mg to about 500 mg per unit dosage form, or Each unit dosage form contains from about 500 mg to about 5000 mg. The formulation may be in the form of a solid, semi-solid, liquid, emulsion, or may be in the form of an emulsion for inhalation administration. It may be adapted for delivery by aerosol or the like.

[0073] The pharmaceutical carrier employed can be, for example, a solid, liquid, or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, and peanuts. Contains cutin, acacia gum, magnesium stearate and stearic acid. Examples of carriers are sugar syrup, peanut oil, olive oil, lower alcohols, and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0074] The pharmaceutical compositions provided herein comprise a solution of the active compound(s) in water. It can be formulated as a liquid or suspension. A suitable surfactant can be included (e.g. Dispersions may also be made with glycerol, liquid polyethylene, etc. It can be prepared in ethylene glycol and mixtures thereof in oils. Additionally, a preservative may be included, for example, to prevent the detrimental growth of microorganisms. .

[0075] Pharmaceutical compositions provided herein that are suitable for injectable use include sterile water. Furthermore, the compositions include such sterile injectable solutions or dispersions. It can be in the form of a sterile powder for extemporaneous preparation of a solution or dispersion. The composition must be stable under the conditions of manufacture and storage; therefore, preferably , must be protected against the contaminating action of microorganisms such as bacteria and fungi. The carrier may be, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol), or the like. and liquid polyethylene glycol), vegetable oils and suitable mixtures thereof. The solvent or dispersion medium may be a solvent or dispersion medium having the same properties as the solvent.

[0076] In addition to the above-mentioned carrier components, the pharmaceutical formulations described above may further comprise one or more Other carrier ingredients (e.g., diluents, buffers, flavoring agents, binders, surfactants, thickeners, Thickeners, lubricants and preservatives (including antioxidants) may be included as appropriate. , and other adjuvants to render the formulation isotonic with the blood of the intended recipient. The compounds provided herein or pharmaceutically acceptable salts or derivatives thereof can be used. The conductor-containing compositions may also be prepared in powder form or liquid concentrate form for dilution. It is possible.

[0077] Fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) or salts or derivatives thereof The conductor can be formulated as a liposome. The fatty acid is a component of the lipid portion of the liposome. or can be entrapped in the aqueous compartment of the liposome. For example, odd-chain fatty acids or very long even-chain fatty acids) or salts or derivatives thereof may also be used. It can be co-formulated with cyclodextrins, such as For example, hydroxypropyl-β-cyclodextrin or sulfobutyl ether cyclodextrin. Dextrin can be mentioned.

[0078] As used herein, fatty acids (such as odd-chain fatty acids or very long even-chain fatty acids) or A composition comprising a salt or derivative thereof in combination with at least one additional active agent is Fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) or salts thereof or the derivative and said at least one further active agent in a single formulation. or may be present in multiple combinations provided together or combined Some formulations may be free of excipients and carriers (e.g., may not contain excipients and carriers). In embodiments, fatty acids (such as odd-chain fatty acids or very long even-chain fatty acids) or The salts or derivatives of may be used together with one or more additional agents in a single composition. For example, fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) can be administered to The compounds of the present invention (e.g., hydroxybenzoates ... and at least one of the additional agents can be administered in a second composition. In a further embodiment, a fatty acid (e.g., an odd-chain fatty acid or a very long even-chain fatty acid) can be used. acid, etc.) or a salt or derivative thereof and said at least one additional active agent and co-packaged in a kit. For example, a drug manufacturer, drug reseller, physician, compounding pharmacy, or A pharmacist or pharmacist may prepare a pharmaceutical product containing the disclosed compound or product and another ingredient for delivery to a patient. A kit containing the above can be provided.

[0079] Some embodiments described herein may be administered in a therapeutically effective amount of the compounds described herein. One or more compounds (e.g., fatty acids (e.g., odd-chain fatty acids or extra-long even-chain fatty acids) fatty acid, etc.) or a pharmaceutically acceptable salt or derivative thereof) and a pharmaceutically acceptable The pharmaceutical composition may include a carrier, diluent, excipient, or combination thereof. The pharmaceutical composition may comprise a fatty acid (e.g., an odd-chain fatty acid or a very long even-chain fatty acid). or a salt or derivative thereof, e.g., at greater than 1%, 2% or more, 3% or more of the composition, 4% or more, 5% or more, 6% or more, 7% or more, 8% or more, 9% or more, 10% or more Above, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70 % or more, 80% or more, 90% or more, 95% or more, or 98% or more In some embodiments, the pharmaceutical composition comprises a plurality of fatty acids (e.g., odd-chain fatty acids). fatty acids and / or very long even-chain fatty acids) or salts thereof or Derivatives may be present in amounts of, for example, greater than 1%, 2% or more, 3% or more, 4% or more, 5% or more of the composition. , 6% or more, 7% or more, 8% or more, 9% or more, 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more It may contain 90% or more, 95% or more, or 98% or more.

[0080] A very long even-chain fatty acid or its salt or derivative and an odd-chain fatty acid or its salt or derivative Formulations are provided that include the derivative and at least one excipient. It is preferred to administer the compound in an oral formulation; however, the compounds shown herein may be administered in an oral formulation. Other routes of administration are also contemplated, as described herein. In some embodiments, the pharmaceutical composition has reported that extra-long even-chain fatty acids and odd-chain fatty acids or salts or derivatives thereof can be used in the preparation of, for example, More than 1% of the composition, 2% or more, 3% or more, 4% or more, 5% or more, 6% or more, 7% or more % or more, 8% or more, 9% or more, 10% or more, 20% or more, 30% or more, 40 % or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, It may comprise 95% or more, or 98% or more, for example, 1% to 98% of the composition. or any amount in between. of the acid or salt or derivative relative to the very long even-chain fatty acid or salt or derivative by weight The standard ratios are 5:95, 10:90, 15:85, 20:80, 25:75, and 30: 70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 6 5:35, 70:30, 75:25, 80:20, 85:15, 90:10, or 95 In some embodiments, the fatty acid present in the formulation can be: comprising 25% to 75% odd-chain fatty acid(s) or salts or derivatives thereof; The remainder comprises very long even-chain fatty acid(s) or salts or derivatives thereof.

[0081] [Food] Fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) or salts or derivatives thereof Foods and other foodstuffs containing esters are provided, provided that the fatty acids in the food The fats provided herein are enriched (e.g., enriched or concentrated) in an amount of The fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) are consumed by the subject. Fatty acids (e.g., odd-chain or very long even-chain fatty acids) may be added to foods to promote Fatty acids (e.g., fatty acids) may be incorporated into one or more components of a food product. For example, odd-chain or very long even-chain fatty acids) may be cooked as ingredients, The above compounds or food containing the above compounds may not be cooked before cooking. The cooking may include, but is not limited to, adding the additives during cooking or after cooking. Cooking, mixing, seasoning, flavoring, blending , boiling, cooking in oil, baking, or any other method known in the art. The enrichment may include other processes. at levels that provide a therapeutic daily dosage of the fatty acids described herein; However, beneficial effects may also be obtained at lower than such dosages. .

[0082] Fatty acids as provided herein (e.g., odd-chain fatty acids or very long even-chain fatty acids) ) or its salts or derivatives can be produced by manipulation of various processes known in nature. for example, by altering the metabolic processes of plants, animals, bacteria or fungi. May occur as a constituent in foods. Fatty acids (e.g., odd-chain fatty acids or a plant, for increasing the concentration of a very long even-chain fatty acid or a salt or derivative thereof; Genetic modification of animals, bacteria, or fungi is contemplated. For example, fatty acids can be modified to at least about 1 %, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about At a concentration of 50% or more, e.g., 1% to 2% or 3% or 4% or 5% or 6% or 7% or 8% or 9% or 10% or 20% or 30% or It can be present in foods at a concentration of 40% or 50%.

[0083] [Indications] Compositions and methods for treating inflammation and various inflammation-related conditions are provided. These conditions include, but are not limited to: anemia of chronic disease, insulin urinary resistance, metabolic syndrome, hypertension, diabetes, non-alcoholic fatty liver disease cardiovascular disease, cancer, various diseases of aging, and neurodegenerative diseases (Alzheimer's disease and and other forms of dementia); metabolic syndrome and various concomitant conditions (II Type 2 diabetes, obesity, prediabetes, glucose intolerance, gestational diabetes mellitus (GDM), fasting hyperglycemia (IFG), impaired adiponectin production, postprandial hyperglycemia, dyslipidemia, postprandial dyslipidemia Diabetes, hyperlipidemia, hypertriglyceridemia, post-hypertriglyceridemia, insulin resistance , Polycystic ovary syndrome (PCOS), Non-alcoholic fatty liver disease (NAFLD), Non-alcoholic fatty liver disease (NAFLD) Nonalcoholic steatohepatitis (NASH), hypoinsulinemia, fatty liver disease, elevated glucose elevated blood sugar levels, elevated insulin levels, elevated LDL-cholesterol levels, elevated High triglyceride levels, low HDL-cholesterol levels, and metabolic disorder iron overload hyperferritinemia and various associated conditions (infections, neoplasms, chronic chronic or acute inflammation, autoimmune diseases, DIOS and other iron overload and iron storage disorders , Still's disease, idiopathic arthritis, hemophagocytic lymphohistiocytosis, macrophage activation syndrome , various liver conditions (including NAFLD, NASH, and hepatocellular carcinoma), anemia of chronic inflammation, and neurodegenerative diseases (including Alzheimer's disease and other forms of dementia); and various anemic disorders (these include hemolytic anemia (including thalassemia, hereditary spherocytosis, cytosis, hereditary elliptocytosis, glucose-6-phosphate dehydrogenase deficiency, pyruvate Acid kinase deficiency, immune hemolytic anemia, alloimmune hemolytic anemia, drug-induced hemolytic anemia, mechanical hemolysis Hemoglobinuria (including but not limited to hemoglobinemia and paroxysmal nocturnal hemoglobinuria), chronic anemia of sexually transmitted diseases (in which case the underlying condition is, for example, an autoimmune disorder (e.g., Crohn's disease) , systemic lupus erythematosus, rheumatoid arthritis, psoriasis, type 1 diabetes, multiple sclerosis and ulcers Neoplastic disorders including cancer (e.g., lymphoma, rhododendron chronic infections (e.g., bacterial infections, viral infections and fungal infections, rheumatoid arthritis, ulcerative colitis, Hodgkin's disease, metabolic syndrome These include, but are not limited to, diabetes (e.g., type 2 diabetes), and other causes of inflammation. (Not performed).

[0084] Aging refers to a series of morphological and functional changes in an organism that occur over time. The term also refers to the decline in biological function after an organism has reached its maximum reproductive potential. Inflammation may contribute to aging through mutations in mitochondrial DNA and other processes. It is believed that they can be linked.

[0085] Subjects suffering from a neurodegenerative condition (e.g., Alzheimer's disease) are those whose dementia is clinically significant. Amyloid beta (a neurodegenerative disease) can cause inflammation long before it is detected by the immune system. It has been reported that the peptides thought to be involved in the proliferation of ATP ultimately cause neuronal damage. This may be correlated with increased inflammation and associated cytokine levels. This may also protect neurons from amyloid beta toxicity. Schmidt et al. (2002) d dementia:a 25-year follow-up of the Ho nolulu-Asia aging study, Ann Neurol, 52:16 8-174, and Blasko et al. (2004), How inflammation can affect the brain and support the brain velopment of Alzheimer's disease in old age:the role of microglia and astrocytes , Aging Cell, 3:169-176.

[0086] In some embodiments, the compositions and methods provided herein treat neurodegenerative disorders. Indicated for the treatment, prevention, prophylaxis or maintenance of a disease. In a further variation of these embodiments, the disease is Alzheimer's disease. In still further variations of these embodiments, the disease is Parkinson's disease. In certain embodiments, the compounds described herein are selected from the group consisting of leukemia, ... The compositions or methods provided can reduce amyloid plaques.

[0087] Inflammation may contribute to hemolysis and anemia of chronic disease. Red blood cells (RBCs), which do not want to be affected but are exposed to cytokines from inflammation, are promoted. In some embodiments, the endothelial cells provided herein are thought to be phagocytosed by the endothelial cells. The compositions and methods are indicated for the treatment, prevention, prophylaxis or maintenance of anemia of chronic disease. will be done.

[0088] Without wishing to be limited by theory, it is believed that the level of odd-chain saturated fatty acid phospholipids in serum, It is believed that increasing it in plasma and cells may reduce inflammation. independent of higher serum cholesterol esters or phospholipid odd-chain saturated fatty acids Therefore, lower levels of inflammation are expected.

[0089] In some embodiments, the compositions and methods provided herein comprise a high ferric Indicated for the treatment, prevention, prophylaxis or maintenance of hyperferritinemia or hyperferritinemia-related conditions can be.

[0090] Ferritin is an important intracellular iron storage protein. Ferritin is used to provide iron for metabolic needs. It is believed that iron in the body contributes to the production of hemoglobin in circulating RBCs. Robin, developing erythroblasts, iron-containing proteins, transporting bound iron, ferritin, and hemoglobin. It can be found in siderin. The total body iron content of an average adult is on the order of a few grams.

[0091] Hyperferritinemia is a blood condition associated with high levels of serum ferritin. However, hyperferritinemia can also be a marker of iron overload. Neoplasms, chronic or acute inflammation, Still's disease, idiopathic arthritis, hemophagocytic lymphohistiocytic Disease, autoimmune disease, metabolic syndrome, type 2 diabetes, macrophage activation syndrome group, various liver conditions (including NAFLD, NASH, and hepatocellular carcinoma), anemia of chronic inflammation and a variety of neurodegenerative diseases (including Alzheimer's disease and other forms of dementia) Elevated ferritin levels are also associated with various inflammatory conditions, and elevated ferritin levels are associated with various inflammatory conditions. Ferritin can be considered an acute phase reactant. Inflammatory symptoms associated with elevated ferritin Symptoms include systemic lupus erythematosus, granulomatosis with polyangiitis, rheumatoid arthritis, and pericarditis. These include scleroderma, inflammatory bowel disease, and graft-versus-host disease. Liver disease with elevated ferritin Conditions include cirrhosis (e.g., due to nonalcoholic steatohepatitis or primary biliary cirrhosis) liver cirrhosis), autoimmune hepatitis, graft-versus-host disease, liver failure due to transient hypotension, toxicities, Intake, alcoholic liver disease, nonalcoholic steatohepatitis, viral hepatitis and acute liver In some situations, hyperferritinemia may have no obvious cause. do.

[0092] Anemic conditions may be classified as normochromic, which generally refers to RBC An anemic condition in which the concentration of hemoglobin in the blood is not pathological and an insufficient number of RBCs is present Anemic conditions are sometimes classified as normocytic, which is Generally, it is understood to be an anemic state in which RBCs are not abnormal in size. Normocytic, normochromic Found anemias include anemia of chronic disease (ACD) and hemolytic anemia.

[0093] RBCs may be removed from the circulation due to aging. However, RBCs experience a decline in metabolic activity, progressive cell shape deformation, membrane reorganization, and acid reflux. Various age-dependent changes may include oxidative damage, microvesicle formation, and exposure of surface cleavage markers. These changes induce phagocytosis by macrophages, which destroys red blood cells. The protease calpain is induced by an increase in cytosolic calcium. It is believed that the ATP may be activated in a process that can lead to an increased rate of RBC destruction. This may lead to anemia.

[0094] Anemia of chronic disease (ACD), also known as anemia of inflammation and anemia of inflammation, is a condition characterized by chronic This is anemia associated with an underlying condition that may suppress red blood cell production in the bone marrow. may shorten the lifespan of red blood cells or affect how the body uses iron. Generally, ACD occurs with mild symptoms or It develops and appears slowly without any associated symptoms.

[0095] Inflammation may play a role in the pathogenesis of ACD. Although we do not wish to be identified, inflammatory cytokines present in many chronic diseases can cause red blood It both reduces sphere production and induces premature degradation of senescent cells. It is thought that this causes anemia because it increases the activity of the reticuloendothelial system. The cytokines and cells regulate iron homeostasis, the generation of erythroid progenitor cells, and the production of erythropoietin. affecting the viability and longevity of RBCs, each of which may contribute to the anemic state. Additionally, ACD may be accompanied by abnormalities in iron homeostasis in the body. Increased uptake and retention of iron within cells of the system may be observed. Subjects with ferritin may have elevated levels.

[0096] In some embodiments provided herein, the subject may be a dolphin. However, the methods, uses and compositions of these embodiments are not intended to be applied to humans. In general, bottlenose dolphins (Tursiops trumpeter) as well as human subjects are intended to Uncatus subjects also suffer from anemia and high insulin, glucose, and triglyceride levels. It is thought that people are more susceptible to metabolic syndrome, including serine, fatty liver disease, and iron overload. Iron overload in dolphins is primarily caused by excessive iron deposition in Kupffer cells of the liver. It can be progressive with age because of the involvement of elevated insulin, lipids, The disease may be associated with mutations in the HFE gene or As in humans, the increase in acute phase proteins is not accompanied by any significant changes in the Iron overload is traditionally treated by phlebotomy, and repeated treatments can increase serum ferritin levels. Iron overload and hyperferric iron in dolphins The underlying cause of ritinemia is unknown.

[0097] In some embodiments, the condition being treated is inflammation.

[0098] In some embodiments, the condition being treated is characterized by a marker as set forth herein. This is inflammation that is indicated by the following.

[0099] In some embodiments, the methods provided herein can be used to detect markers of inflammatory components. - is regulated when the marker is causing clinical symptoms.

[0100] In some embodiments, the methods provided herein alleviate the symptoms of inflammation.

[0101] In some embodiments, the methods provided herein reduce the risk of inflammation. do.

[0102] In some embodiments, the methods provided herein involve measuring the concentration of HCl in serum, plasma, or Increases the level of odd-chain fatty acids in red blood cell membranes.

[0103] In some embodiments, the methods provided herein involve measuring the concentration of HCl in serum, plasma, or In a further embodiment, the serum In the presence of a deficiency of one or more odd-chain fatty acids, the level of very long even-chain fatty acids in plasma or red blood cell membranes is It may increase after administration of fatty acids or their salts or derivatives.

[0104] In some embodiments, the condition being treated is anemia of chronic disease.

[0105] In some embodiments, the condition being treated is an autoimmune disease.

[0106] In some embodiments, the methods provided herein provide for the determination of very long even-chain lipids in serum. Increases acid levels.

[0107] In some embodiments, the compositions and methods provided herein treat markers of inflammation. In certain embodiments, the marker is a protein present in serum, plasma, or red blood cells. Odd-chain fatty acid percentage in the erythrocyte membrane, serum concentration, plasma concentration, or erythrocyte membrane concentration serum, plasma or erythrocyte membrane odd-chain fatty acids, erythrocyte sedimentation rate, alkaline phosphatase phatase, serum ferritin, CRP (C-reactive protein), IL-6 and TNFα (as well as other cytokines associated with insulin resistance), c-Jun N-terminal kinase ( JNK), ATM (ataxia telangiectasia mutated), or monocyte chemoattractant protein-1. In some embodiments, odd-chain fatty acids are measured as constituents of glycolipids. In another embodiment, odd-chain fatty acids are measured as constituents of phospholipids. In a further embodiment, the marker is a very long even-chain fatty acid fragment in serum or red blood cell membranes. In this case, the serum concentration of very long even-chain fatty acids and the total very long even-chain fatty acids in serum are shown.

[0108] In some embodiments, the methods provided herein involve measuring the concentration of a marker of inflammation. Those skilled in the art will be able to use various methods, including but not limited to, those described herein. Various suitable methods for such measurements may be performed, including but not limited to: cormorant.

[0109] As used herein, a given fatty acid (e.g., odd-chain fatty acid or very long even-chain fatty acid) at predetermined intervals or at intervals left to the discretion of the subject. A method is provided.

[0110] In some embodiments, the compounds and methods provided herein provide a method for treating rheumatoid arthritis in serum, Serum, plasma, or red blood cell odd-chain fatty acids relative to total fatty acids in plasma or red blood cell membranes Each may result in a threshold percentage in the film. For example, the threshold value may be about 0.05% or may be less than or equal to 90% or more, e.g., at least about 0.05%, at least about 0.1%, at least about 0.2%, at least about 0.3%, a small amount at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0. 7%, at least about 0.8%, at least about 0.9%, at least about 1.0%, at least at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, At least about 1.5%, at least about 1.6%, at least about 1.7%, at least about 1 0.8%, at least about 1.9%, at least about 2.1%, at least about 2.2%, less Both are approximately 2.3%, at least approximately 2.4%, at least approximately 2.5%, and at least approximately 2.6% , at least about 2.7%, at least about 2.8%, at least about 2.9%, at least about 3.0%, at least about 3.5%, at least about 4.0%, at least about 4.5%, at least at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 2 5%, at least about 30%, at least about 35%, at least about 40%, at least about 4 5%, at least about 50%, at least about 60%, at least about 70%, at least about 8 It may be 0%, at least about 90%, or greater than 90%.

[0111] In some embodiments, the compounds and methods provided herein comprise an odd-chain lipid. Baseline serum or plasma concentrations of fatty acids or red blood cell membrane concentrations of odd-chain fatty acids Line values (e.g., pretreatment values in treated patients or values in specific patient populations) For example, serum or plasma odd-chain fatty acids or odd-chain fatty acids in the erythrocyte membrane concentration is at least about 1 μg / ml, at least about 2 μg / ml, at least about 3 μg / ml, at least At least about 4 μg / ml, at least about 5 μg / ml, at least about 6 μg / ml , at least about 7 μg / ml, at least about 8 μg / ml, at least about 9 μg / ml, at least about 10 μg / ml, at least about 15 μg / ml, at least about 20 μg / ml, at least about 25 μg / ml, at least about 30 μg / ml, at least about 35 μg / ml, at least about 40 μg / ml, at least about 45 μg / ml, at least about 50 μg / ml, or 50 μg / ml In some embodiments, serum concentrations of odd-chain fatty acids may be increased by more than 100%. The concentrations of the erythrocyte membranes of the odd-chain fatty acids are compared with the baseline values (e.g., (pre-treatment values in patients or typical values observed in a particular patient population) At least about 0.01 × 10 -4 M only, at least about 0.05 x 10 -4 Only M, a little At least about 0.1 × 10 -4 M only, at least about 0.2 × 10 -4 Only M, at least Approximately 0.3×10 -4 M only, at least about 0.4 × 10 -4 M only, at least about 0.5 x10 -4 M only, at least about 0.6 × 10 -4 M only, at least about 0.7 × 10 - 4 M only, at least about 0.8 × 10 -4 M only, at least about 0.9 × 10 -4 Only M , at least about 1 x 10 -4 M only, at least about 2 x 10 -4 Only M or at least Also about 3 x 10 -4 M may increase.

[0112] In some embodiments, the compounds and methods provided herein also provide a therapeutic effect in serum. or an increase in total odd-chain fatty acids in plasma or in erythrocyte membranes. For example, the total odd-chain fatty acids in serum or the total odd-chain fatty acids in red blood cell membranes may be Baseline values (e.g., pre-treatment values in a patient being treated, or values in a specific patient) at least about 5 μg / ml higher than the typical value found in the population, by about 6 μg / ml, by at least about 7 μg / ml, by at least about 8 μg / ml; At least about 9 μg / ml, at least about 10 μg / ml, at least about 15 μg / ml μg / ml, at least about 20 μg / ml, at least about 25 μg / ml, At least about 30 μg / ml, at least about 35 μg / ml, at least about 40 μg / ml μg / ml, at least about 45 μg / ml, at least about 50 μg / ml, At least about 60 μg / ml, at least about 70 μg / ml, at least about 80 μg / ml g / ml, at least about 90 μg / ml, at least about 100 μg / ml, At least about 150 μg / ml, at least about 200 μg / ml, at least about 250 μg / ml or less, at least about 300 μg / ml or less, at least about 350 μg / ml or less ml, at least about 400 μg / ml, at least about 450 μg / ml, may be increased by at least about 500 μg / ml or by more than 500 μg / ml. be.

[0113] In some embodiments, the compounds and methods provided herein are useful for detecting inflammatory bowel disease in serum or The ratio of odd-chain fatty acids in serum, plasma, or red blood cell membranes to total fatty acids in the red blood cell membranes baseline values in a patient (e.g., pretreatment values in a treated patient, or values in a specific Each may result in an increase above the typical value seen in the patient population. For example, odd-chain fatty acids in serum, plasma, or red blood cell membranes are elevated relative to baseline values (e.g., Pretreatment values in treated patients or values observed in a particular patient population at least about 0.01%, at least about 0.05%, at least about Also, by at least about 0.1%, by at least about 0.2%, by at least about 0.3%, by at least by about 0.4%, by at least about 0.5%, by at least about 0.6%, by at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1 %, at least about 1.1%, at least about 1.2%, at least about 1.3% only, at least about 1.4%, at least about 1.5%, at least about 1.6% by at least about 1.7%, by at least about 1.8%, by at least about 1.9% , by at least about 2%, by at least about 2.1%, by at least about 2.2%, at least by about 2.3%, at least by about 2.4%, at least by about 2.5%, at least about 2.6%, at least about 2.7%, at least about 2.8%, at least At least about 2.9%, at least about 3%, at least about 3.5%, at least about 4% %, by at least about 4.5%, by at least about 5%, or by more than 5%. This may be the case.

[0114] In some embodiments, the compounds and methods provided herein provide elevated May result in a decrease in the erythrocyte sedimentation rate.

[0115] In some embodiments, the compounds and methods provided herein provide elevated May result in a decrease in alkaline phosphatase.

[0116] In some embodiments, the compounds and methods provided herein are For example, serum ferritin may be elevated below baseline levels. (e.g., pretreatment values in treated patients or values recognized in a particular patient population) at least about 10 ng / ml higher than the general value (typically considered) and at least about 100 ng / ml higher than the / ml, at least about 200ng / ml, at least about 300ng / ml, At least about 400 ng / ml, at least about 500 ng / ml, at least about 600ng / ml or less, at least about 700ng / ml or less, at least about 800ng / ml, at least about 900 ng / ml, at least about 1000 ng / ml, At least about 1100 ng / ml, at least about 1200 ng / ml, at least at least about 1300 ng / ml, at least about 1400 ng / ml, at least about 15 00ng / ml, at least about 2000ng / ml, at least about 2500ng / ml, at least about 3000ng / ml, at least about 3500ng / ml At least about 4000 ng / ml, at least about 4500 ng / ml, at least about 5000 ng / ml, at least about 6000 ng / ml, at least about 7000ng / ml or less, at least about 8000ng / ml or less, at least about 9000 ng / ml, at least about 10000ng / ml, or 10000ng / ml It may be reduced by as much as

[0117] In some embodiments, the compounds and methods provided herein comprise a specified level This may result in a decrease in serum ferritin below the normal range. The concentration of α-glucan is less than about 20,000 ng / ml, less than about 15,000 ng / ml, and less than about 12,000 ng / ml. less than about 10000 ng / ml, less than about 8000 ng / ml, less than about 50 less than 00ng / ml, less than about 2000ng / ml, less than about 1000ng / ml, or or may be reduced to less than about 500 ng.

[0118] In some embodiments, the odd-chain fatty acid is an odd-chain fatty acid or all odd-chain fatty acids. to maintain the total serum or plasma percentage of long chain fatty acids above a predetermined threshold value. In various variations of these embodiments, the odd-chain fatty acid is heptadecanoic acid In a further variation, the odd-chain fatty acid is The serum phospholipid percentage of chain fatty acids was about 0.1%, about 0.2%, about 0.3%, about 0.4% %, approx. 0.5%, approx. 0.6%, approx. 0.7%, approx. 0.8%, approx. 0.9%, approx. 1%, approx. 1.2 %, approximately 1.4%, approximately 1.6%, approximately 1.8%, approximately 2%, approximately 2.2%, 2.4% or 2.6 It is administered to maintain the level above %.

[0119] In some embodiments, the compounds and methods provided herein are useful for detecting inflammatory bowel disease in serum or The ratio of very long even-chain fatty acids to the total fatty acids in serum, plasma, or erythrocyte membranes For example, the threshold value may be about 0.05% or less. It may be from less than 100% up to 90% or more, for example at least about 0. 0.5%, at least about 0.1%, at least about 0.2%, at least about 0.3%, less Both are about 0.4%, at least about 0.5%, at least about 0.6%, and at least about 0.7% , at least about 0.8%, at least about 0.9%, at least about 1.0%, at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, at least at least about 1.5%, at least about 1.6%, at least about 1.7%, at least about 1.8% %, at least about 1.9%, at least about 2.1%, at least about 2.2%, at least About 2.3%, at least about 2.4%, at least about 2.5%, at least about 2.6%, at least about 2.7%, at least about 2.8%, at least about 2.9%, at least about 3. 0%, at least about 3.5%, at least about 4.0%, at least about 4.5%, at least At least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9% , at least about 10%, at least about 15%, at least about 20%, at least about 25% , at least about 30%, at least about 35%, at least about 40%, at least about 45% , at least about 50%, at least about 60%, at least about 70%, at least about 80% , at least about 90%, or greater than 90%.

[0120] In some embodiments, the compounds and methods provided herein comprise an ultra-long even number in serum or plasma concentrations of even-chain fatty acids or in erythrocyte membrane concentrations of very-long even-chain fatty acids baseline values (e.g., pretreatment values in treated patients, or values in specific patients) may result in an increase in blood pressure (above the typical value observed in the general population). The concentration of very long even-chain fatty acids in the supernatant or very long even-chain fatty acids in the erythrocyte membrane is at least about 0. 0.01 μg / ml, at least about 0.05 μg / ml, at least about 0.1 μg / ml, by at least about 0.4 μg / ml, by at least about 1 μg / ml, Both are about 2 μg / ml, at least about 3 μg / ml, and at least about 4 μg / ml. by at least about 5 μg / ml, by at least about 6 μg / ml, by at least about 7 μg / ml g / ml, at least about 8 μg / ml, at least about 9 μg / ml, At least about 10 μg / ml, at least about 15 μg / ml, at least about 20 μg / ml ml, at least about 25 μg / ml, at least about 30 μg / ml, At least about 35 μg / ml, at least about 40 μg / ml, at least about 45 μg / ml ml, by at least about 50 μg / ml, or by more than 50 μg / ml In some embodiments, the serum concentration of very long even-chain fatty acids or The erythrocyte membrane concentrations of even-chain fatty acids are compared with baseline values (e.g., in patients undergoing treatment). (pre-treatment values or typical values observed in a particular patient population) is approximately 0.001 x 10 -4 M only, at least about 0.005 x 10 -4 Only M, at least Also about 0.05 x 10 -4 M only, at least about 0.01 x 10 -4 Only M, at least about 0.05×10 -4 M only, at least about 0.1 x 10 -4 M only, at least about 0.2 x10 -4 M only, at least about 0.3 × 10 -4 M only, at least about 0.4 × 10 - 4 M only, at least about 0.5 × 10 -4 M only, at least about 0.6 × 10 -4 Only M , at least about 0.7 × 10 -4 M only, at least about 0.8 × 10 -4 Only M, less Both are approximately 0.9 x 10 -4 M only, at least about 1 x 10 -4M only, at least about 2 x 1 0 -4 M only, or at least about 3 × 10 -4 M may increase.

[0121] In some embodiments, the compounds and methods provided herein also provide a therapeutic effect in serum. or an increase in total very-long even-chain fatty acids in plasma or total very-long even-chain fatty acids in erythrocyte membranes For example, the total very long even-chain fatty acids in serum or the total very long even-chain fatty acids in red blood cell membranes may Even-chain fatty acids are measured at baseline values (e.g., pre-treatment values in treated patients, or or the typical value observed in a particular patient population) by at least about 0.05 μg / ml, at least about 0.1 μg / ml, at least about 0.5 μg / ml, At least about 1 μg / ml, at least about 5 μg / ml, at least about 6 μg / ml, at least about 7 μg / ml, at least about 8 μg / ml, at least Only about 9 μg / ml, at least about 10 μg / ml, at least about 15 μg / ml by at least about 20 μg / ml, by at least about 25 μg / ml, by at least about Only 30 μg / ml, at least about 35 μg / ml, at least about 40 μg / ml by at least about 45 μg / ml, by at least about 50 μg / ml, by at least about Only 60 μg / ml, at least about 70 μg / ml, at least about 80 μg / ml by at least about 90 μg / ml, by at least about 100 μg / ml, by at least By about 150 μg / ml, by at least about 200 μg / ml, by at least about 250 μg / ml, at least about 300 μg / ml, at least about 350 μg / ml, At least about 400 μg / ml, at least about 450 μg / ml, at least about It may be increased by 500 μg / ml or by more than 500 μg / ml.

[0122] In some embodiments, the compounds and methods provided herein provide a method for treating rheumatoid arthritis in serum, Ultra-long-chain fatty acids in serum, plasma, or red blood cell membranes relative to total fatty acids in plasma or red blood cell membranes Baseline values for the chain fatty acids (e.g., pre-treatment values in treated patients, or or typical values seen in a particular patient population, respectively. For example, serum or red blood cell membrane very long even-chain fatty acids may be elevated above baseline values ( For example, pretreatment values in treated patients or values observed in a particular patient population. at least about 0.01%, at least about 0.05%, At least about 0.1%, at least about 0.2%, at least about 0.3%, At least by about 0.4%, at least by about 0.5%, at least by about 0.6%, at least by about 0.7%, at least by about 0.8%, at least by about 0.9%, At least about 1%, at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, at least about 1.5%, at least about 1 .6%, at least about 1.7%, at least about 1.8%, at least about 1. Only 9%, at least about 2%, at least about 2.1%, at least about 2.2% by at least about 2.3%, by at least about 2.4%, by at least about 2.5% , at least about 2.6%, at least about 2.7%, at least about 2.8%, At least about 2.9%, at least about 3%, at least about 3.5%, by at least about 4%, by at least about 4.5%, by at least about 5%, or by more than 5% It may be increased.

[0123] In some embodiments, the very long even-chain fatty acid is The serum phospholipid percentage or plasma phospholipid percentage of all very long even-chain fatty acids was calculated based on the In various variations of these embodiments, In a further variation, the very long even chain fatty acid is behenic acid. The serum phospholipid percentage of the very long even-chain fatty acid or all very long even-chain fatty acids is about 0. 0.1%, approximately 0.2%, approximately 0.3%, approximately 0.4%, approximately 0.5%, approximately 0.6%, approximately 0.7%, Approximately 0.8%, approximately 0.9%, approximately 1%, approximately 1.2%, approximately 1.4%, approximately 1.6%, approximately 1.8%, It is administered to maintain it above about 2%, about 2.2%, 2.4% or 2.6%.

[0124] In some embodiments, the compositions or methods provided herein improve red blood cell counts. For example, red blood cell count levels may increase above baseline values (e.g., For example, pretreatment values in treated patients or values observed in a particular patient population. at least about 0.1 cells / µL higher than the typical value (typical value for by at least about 0.3 cells / μL, by at least about 0.4 cells / μL, At least about 0.5 cells / μL, at least about 0.6 cells / μL, at least about 0. No more than 7 cells / μL, no more than about 0.8 cells / μL, no more than about 0.9 cells / μL at least about 1 cell / μL, at least about 1.2 cells / μL, at least At least about 1.4 cells / μL, at least about 1.6 cells / μL, or at least about 2 cells / μL The number of cells / μL may be increased.

[0125] [Combination therapy] In some embodiments, the compounds disclosed herein (e.g., odd-chain fatty acids) or a salt or derivative thereof, or a very long even-chain fatty acid or a salt or derivative thereof or a pharmaceutical comprising a compound described herein or a salt or derivative thereof. The pharmaceutical compositions may be used in combination with one or more additional active agents. Combination of odd-chain fatty acids or very long even-chain fatty acids or their salts or derivatives with compounds or odd-chain fatty acids or their salts or derivatives, very long even-chain fatty acids or Additional active agents that can be used in combination with compositions containing salts or derivatives of the compounds Examples of suitable agents include those currently used to treat various conditions listed herein. Drugs and pharmaceutical agents as otherwise known to the medical and scientific community, but Not limited to these.

[0126] In some embodiments, an odd-chain fatty acid, or a salt or derivative thereof, an extra-long even-chain A compound of a fatty acid or its salt or derivative, or an odd-chain fatty acid or its salt The composition containing the compound of the very long even-chain fatty acid or its salt or derivative is also May be used in conjunction with one, two, three or more additional active agents as described herein. Such agents may include a second fatty acid (e.g., an odd-chain fatty acid or very long even-chain fatty acids, etc.) or their salts or derivatives. In some embodiments, the composition comprises at least one odd-chain fatty acid or a salt or derivative thereof, and at least one very long even-chain fatty acid or a salt or derivative thereof may include:

[0127] In some embodiments, an odd-chain fatty acid, or a salt or derivative thereof, an extra-long even-chain A compound of a fatty acid or its salt or derivative, or an odd-chain fatty acid or its salt The composition containing the compound of the very long even-chain fatty acid or its salt or derivative is Diabetic syndrome, hyperferritinemia, inflammation, oxidative stress, or anemia For the treatment, prevention, control or prophylaxis of the conditions set forth herein, including, or Use in combination with another agent(s) for modulation of markers of the condition can be administered or ingested. In some embodiments, the condition is hemolytic anemia (including thalassemia, genetic Hereditary spherocytosis, hereditary elliptocytosis, glucose-6-phosphate dehydrogenase deficiency , pyruvate kinase deficiency, immune hemolytic anemia, alloimmune hemolytic anemia, drug-induced hemolytic anemia , mechanical hemolytic anemia, and paroxysmal nocturnal hemoglobinuria anemia of chronic disease (in which case the underlying condition is not, for example, an autoimmune disorder (e.g., Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and ulcerative colitis neoplastic disorders, including cancer (e.g., lymphoma and Hodgkin's disease), and long-term infectious diseases (e.g., bacterial, viral and fungal infections), rheumatoid arthritis, ulcerative colitis Colitis, Hodgkin's disease, metabolic syndrome, diabetes (e.g., type 2 diabetes), and Other causes of diffuse inflammation may be mentioned), anemia, aplastic anemia (including congenital These include aplastic anemia, Diamond-Blackfan anemia, and Fanconi anemia. These include, but are not limited to, iron deficiency anemia, anemia with abnormal RBC size (including (including but not limited to megaloblastic anemia and microcytic anemia), vitamin deficiency anemia (including, but not limited to, pernicious anemia), anemia of RBC mutations ( This includes, but is not limited to, thalassemia, sideroblastic anemia, and sickle cell anemia. For example, the fatty acids disclosed herein (e.g., odd-chain fatty acids) can be or very long even-chain fatty acids) are iron chelators, albiglutide, alegristat, Zar, balaglitazone, canagliflozin, CJ-30001 (CJ Cheiljed ang Corporation), CJ-30002(CJ Cheiljedang Corporation), Diamyd® (glutamic acid decarboxylase) rhGAD65), dulaglutide, exendin 4, gemigliptin (gem igliptin, lixisenatide, lobeglitazone , Shengke I (Tibet Pharmaceuticals), S K-0403 (Sanwa Kagaku Kenkyusho), Teneligliptin, Teplizumab, tofogliflozin, acarbose, alogliptin benzoate, chlorpromazine Lopamide, Diab II (Biotech Holdings), Exenatide, Glycerol Benclamide, gliclazide, glimepiride, glipizide, gliquidone, glisentide ( glisentide), glisolamide, HL-002 (H anAII Biopharma), insulin (human), insulin, insulin ana Log (Eli Lilly®), insulin aspart, insulin detemir , insulin glargine, insulin lispro, Janumet®, linagry putin, liraglutide, metformin, miglitol, mitiglinide, nateglinide, N ovo Mix 30® (Novo Nordisk®), Piog Ritazon, pramlintide, repaglinide, rosiglitazone maleate, saxaglip tin, sitagliptin, Tresiba, tolazamide, tolbutamide, vildagliptin , voglibose, bezafibrate, diflunisal, cinnamic acid, carbutamide, glibri glibenclamide, glibornuride, glyhexamide 1 selected from phenbutamide and tolcyclamide or may be used in combination with one or more drugs, such as sulfonylureas, Non-sulfonylurea secretagogues, glucagon-like peptides, exendin-4 polypeptide beta-3 adrenergic receptor agonist, PPAR agonist, dipeptidyl peptidase Glucosidase IV inhibitors, biguanides, alpha-glucosidase inhibitors, immunomodulators, Statins and statin-containing combinations, angiotensin-converting enzyme inhibitors, adenosine A 1 receptor agonist, adenosine A2 receptor agonist, aldosterone antagonist , alpha 1 adrenergic receptor antagonist, alpha 2 adrenergic receptor antagonist agonist, alpha 2 adrenergic receptor agonist, angiotensin receptor antagonist Antioxidant, ATPase inhibitor, atrial peptide agonist, beta-adrenergic Calcium channel agonists, calcium channel antagonists diguanides, diuretics, dopamine D1 receptor agonists, endopeptidase inhibitors Antitoxins, endothelin receptor antagonists, guanylate cyclase stimulators, phosphodiesterase inhibitors Bacterial phosphodiderivativease V inhibitor, protein Kinase inhibitors, Cdc2 kinase inhibitors, renin inhibitors, thromboxane synthase inhibitors Antihypertensives, vasopeptidase inhibitors, vasopressin I antagonists, vasopressin II antagonists agonists, angiogenesis inhibitors, advanced glycation end product inhibitors, bile acid binders, bile acid transport inhibitors, bone Formation stimulator, apolipoprotein A1 agonist, DNA topoisomerase inhibitor, cholecystosine Sterol absorption inhibitor, cholesterol antagonist, corderibatibile (chol derivativeyl) transport protein antagonist, cytokine synthesis inhibitor Antineoplastic agents, DNA polymerase inhibitors, dopamine D2 receptor agonists, endothelin receptors antagonist, growth hormone antagonist, insulin sensitizer, lipase inhibitor agent, lipid peroxidation inhibitor, lipoprotein A antagonist, microsomal transport protein inhibitors, microsomal triglyceride transfer protein inhibitors, nitric oxide synthase inhibitors agents, oxidizing agents, phospholipase A2 inhibitors, radical-forming agonists, platelet aggregation antagonists Nist, prostaglandin synthase stimulator, reverse cholesterol transport activator, rh o kinase inhibitor, selective estrogen receptor modulator, squalene epoxidase inhibitor , squalene synthase inhibitor, thromboxane A2 antagonist, amylin agonist Cannabinoid receptor antagonist, cholecystokinin A agonist, adrenal cortical stimulator Insulin-releasing hormone agonist, dopamine uptake inhibitor, G protein-coupled receptor modulator Agents, glutamate antagonists, glucagon-like peptide-1 agonists, lipase inhibitors , melanin-concentrating hormone receptor antagonist, nerve growth factor agonist, neuropeptide Neuropeptide Y agonists, neuropeptide Y antagonists, SNRIs, protein tyrosine kinase inhibitors and serotonin 2C receptor agonists. It can be used with one or more drugs that are For example, central nervous system agents that affect neurotransmitters or neuronal ion channels (including The drugs used were antidepressants (bupropion), noradrenaline reuptake inhibitors (GW320659 ), selective serotonin 2c receptor agonist, selective 5HT2c receptor agonist, anticonvulsant Anticonvulsants (topiramate, zonisamide), dopamine antagonists, cannabinoid-1 receptor CB-1 receptor antagonists (including rimonabant); Leptin / insulin / CNS pathway agents (including leptin analogs, leptin transport enhancers) agents and / or leptin receptor agonists, ciliary neurotrophic factor (Axokine), Propeptide Y antagonists and agouti-related peptide antagonists, protease inhibitors Pyomelanocortin-regulated transcript enhancer and cocaine-amphetamine-regulated transcript enhancer , α-melanocyte-stimulating hormone analog, melanocolitin n)-4 receptor agonists, and drugs that affect insulin metabolism / activity [this Protein tyrosine phosphatase IB inhibitors, peroxisome proliferator-activated receptor-gamma receptor antagonist, short-acting bromocriptine (ergocet ( ergoset), somatostatin agonists (octreotide) and adiponectin Contains Acrp30 (Famoxin or fatty acid metabolic oxidation inducer) Gastrointestinal neurotransmitter agents (including cholecystokinin activity (CCK), PYY activity, Drugs that increase NPY and PP activity, and drugs that increase glucagon-like peptide-1 activity drugs that cause steroid use (exendin-4, dipeptidyl peptidase IV inhibitors), as well as Drugs that reduce vasodilator activity, as well as amylin analogs (pramlintide) ); drugs that can increase resting metabolic rate (selective beta-3 agonists / agonists, uncoupling proteins) protein homologs and thyroid receptor agonists); other more diverse agents (including melanoma, Nerve-concentrating hormone antagonist, phytostanol analogue G, functional oil, P57, amylase inhibitor, growth hormone fragment, sulfate dehyde A synthetic analog of lepiandrosterone, a 11B-hydroxysteroid dehydrogenase in adipocytes Antagonist of steroidogenase type 1 activity, corticotropin-releasing hormone agonist , inhibitors of fatty acid synthesis (cerulenin and C75), carboxypeptidase inhibitors, Indanone / indanol compounds, aminosterols (trodusquemine squemine / trodulamine, and other gastrointestinal thiazol-2-yltransferase inhibitors (ATL962); amphetamines (e.g., dextromethorphan); amphetamines); other sympathomimetic adrenergic agents (including phentermine, amine, benzphetamine, phendimetrazine, mazindol and diethylpropion or one or more selected from the following: May be used with several medications: ecopipam; oxint Modulin (OM); an inhibitor of glucose-dependent insulinotropic polypeptide (GIP) anti-inflammatory drugs;gastrin-releasing peptide;neuromedin B;enterostatin;amfebutam amfebutamone, SR-58611;CP-045598;AOD-0 604;QC-BT16;rGLP-1;1426(HMR-1426);N-5984 ;ISIS-113715;solabegron;SR-14777 8; Org-34517; Melanotan-II; Cetilistat; c-2735;c-5093;c-2624;APD-356;Radafaxine (rad afaxine); fluasterone; GP-389255; 856464;S-2367;AVE-1625;T-71;Oleoyl-estrone( oleoyl-estrone); Peptide YY[3-36] (intranasal); Androgens PYY3-36 receptor agonist; DOV-102677; Tagatose; SLV-3 19;1954(Aventis Pharma AG);Oxyntomodulin, Th iakis; Bromocriptine, PLIVA; Diabetes / hyperlipidemia therapy, Yissum; C KD-502; Thyroid receptor beta agonist; Beta-3 adrenergic receptor agonist CDK-A agonist; Galanin antagonist; Dopamine D1 D2 agonist; Melanocortin modulators; verongamine; neuropeptide Y antagonist; melanin-concentrating hormone receptor antagonist; dual PPAR alpha / Gamma agonist; CGEN-P-4; kinase inhibitor; human MCH receptor antagonist GHS-R antagonist; Ghrelin receptor agonist; DG70 inhibitor; Cotinine ;CRF-BP inhibitor;Urocortin agonist;UCL-2000;Inpentamine ( impentamine); beta-3 adrenergic receptor; pentapeptide MC4 a agonist; trodusquemine; GT-2016; C-75 ;CPOP;MCH-1 receptor antagonist;RED-103004; Aminosterols; Orexin-1 antagonists; Neuropeptide Y5 receptor antagonists agonist; DRF-4158; PT-15; PTPase inhibitor; A37215; SA -0204; Glycolipid metabolite; MC-4 agonist; Produlestan tan);PTP-1B inhibitor;GT-2394;Neuropeptide Y5 antagonist ; Melanocortin receptor modulator; MLN-4760; PPAR gamma / delta dual agonist NPY5RA-972; 5-HT2C receptor agonist; Neuropeptide Y5 receptor receptor antagonist (phenylurea analog); AGRP / MC4 antagonist; Neuropeptide Y5 receptor antagonist (benzimidazole); glucocorticoid antagonist;MCHR1 antagonist;acetyl-CoA carboxylase inhibitor; R-1496; HOB1 regulator; NOX-B11; peptide YY3-36 (eligen(e ligen); 5-HT1 modulator; pancreatic lipase inhibitor; GRC-1087; CB-1 Antagonist; MCH-1 antagonist; LY-448100; Bombesin BRS3 Agonist; Ghrelin antagonist; MC4 antagonist; Stearoyl CoA dess Hormone-sensitive lipase modulator; PPAR pan-agonist; EP-01492 Inhibitors; Fatty acid binding protein 4 inhibitors; Thiolactone derivatives; Protein tyrosine phosphatase inhibitors PHATASE IB INHIBITOR; MCH-1 ANTAGONIST; P-64; PPARγ LIGAND ;Melanin-concentrating hormone receptor antagonist;Thiazole gastroprokinetic agent (gastr oprokinetic);PA-452;T-226296;A-331440;Immunology Drug vaccines; diabetes / obesity treatments (Bioagency, Biofrontera D iscovery GmbH);P-7(Genfit);DT-011M;PTP1B Inhibitors; Antidiabetic peptide conjugates; KATP agonists; Antiobesity agents (Lex icon); 5-HT2 agonist; MCH-1 receptor antagonist; GMAD-1 / GMAD-2; STG-a-MD; angiogenesis inhibitor; G protein-coupled receptor agonist nicotine-like therapeutics (ChemGenex); anti-obesity agents (Abbott); melanin aggregation Hormone; GW-594884A; MC-4R agonist; Histamine H3 antagonist Orphan GPCR modulators; MITO-3108; NLC-002; HE-2300 ;IGF / BBP-2-13;5-HT2C agonist;ML-22952;Neurope Peptide Y receptor antagonist; AZ-40140; Anti-obesity therapy (Nisshin Fl our);GNTI;melanocortin receptor modulator;alpha-amylase inhibitor;base TA-3 adrenergic receptor agonist; ob gene product (Eli Lilly & Co.) ;SWR-0342-SA;SWR-0335;SP-18904;Oral insulin mimetic Anti-obesity agent (7TM Pharma); beta-hydroxysteroid dehydrogenase HSD inhibitors; QRX-431; E-6776; RI-450; melanocortin -4 antagonist; melanocortin 4 receptor agonist; anti-obesity agent (CuraGen );Leptin mimetics;A-74498;Second-generation leptins;NBI-103;CL-31 4698;CP-114271;Beta-3 adrenergic receptor agonist;NMI-8 739;UCL-1283;BMS-192548;CP-94253;PD-1601 70;Nicotinic agonists;LG-100754;SB-226552;LY-3551 24;CKD-711;L-751250;PPAR inhibitor;G protein therapeutic agent;Obesity Therapy (Amylin Pharmaceuticals Inc.);BW-1229; Monoclonal antibody (ObeSys / CAT); L-742791; (S)-Sibutramine MBU-23; YM-268; BTS-78050; tubby-like protein gene Genomics (Eating Disorders; Allelix / Lilly); MS-706; GI-264 879A; GW-409890; FR-79620 analog; Obesity therapy (Hybrid nics SA);ICI-198157;ESP-A;5-HT2C agonist;PD -170292;AIT-202;LG-100641;GI-181771;Anti-obesity treatment Therapeutic (Genzyme); Leptin Modulator; GHRH Mimetics; Obesity Therapy (Yamanou) chi Pharmaceutical Co.Ltd.);SB-251023;CP -331684;BIBO-3304;Cholesten-3-ones;LY-362884; BRL-48962; PY-1 antagonist; A-71378; RTM-Zydesme Tilsibutramine (didesmethylsibutramine); Antiobesity agent (B Dr. Stolt-Myers Squibb Co.; Anti-obesity agent (Ligand Ph pharmaceuticals Inc.);LY-226936;NPY antagonist ;CCK-A agonist;FPL-14294;PD-145942;ZA-7114; CL-316243;SR-58878;R-1065;BDBP-3226;HP-2 28; talibegron; FR-165914; AZM-008; AZM-016;AZM-120;AZM-090;AZM-131;AZM-132; AZM-134;AZM-127;AZM-083;AZM-115;AZM-140; Vomeropherin; BMS-187257; D-3800; Gene discovery (Axys / Glaxo); BRL-26830A; SX-013; ERR study Cutting agent; Adipsin; AC-253; A-71623; A-68552; BMS-2102 85;TAK-677;MPV-1743;Obesity treatment (Modex);GI-2485 73; Exopipam; SSR-125180; Antiobesity agent (Mel acure Therapeutics AB);BRL-35135;SR-1461 31;P-57;CGP-71583A;RF-1051;BMS-196085;Mani Manifaxine; DMNJ (Korea Research Institute Institute of Bioscience and Biotechnology) ;BVT-5182;LY-255582;SNX-024;Galanin antagonist; Neurokinin-3 antagonist; dexfenfluramine; mazindol; diethyl Propionate; Phendimetrazine; Benzphetamine; Amphebutamone; Sertraline ;AOD-9604;ATL-062;BVT-933;GT389-255;SLV3 19;HE-2500;PEG-axokine;L-796568; and ABT-239; rimonabant, sibutramine, orlistat, PYY or its analogs Analogs, CB-1 antagonists, leptin, phentermine and exendin analogs GPR119 antagonists (e.g., anandamide; AR-231,453; MB X-2982; oleoylethanolamide; PSN-365,963; PSN-632 ,408; Palmitoylethanolamide; GPR120 agonist; GPR40 agonist and SGLT2 inhibitors. In addition, the fatty acid or salt or derivative as provided herein may be selected from the following: It can be used in combination with one or more of the following drugs: Altoprev ( Vastatin), Crestor (rosuvastatin), Lescol (fluvastatin), Lipitor (atorvastatin), Livalo (pitavastatin), Pravac hol (pravastatin), Zocor (simvastatin), antiplatelet drugs, beta-blockers , ACE inhibitors, calcium channel blockers, diuretics, anticoagulants, aspirin, bile acid sequestrants Antigens, ezetimibe, fibrates, glycoprotein Ilb / IIIa receptor inhibitors, Niacin (nicotinic acid), nitrates, platelet inhibitors, thrombolytics, lisinopril (oral), Atenolol (oral), Bystolic (oral), Diovan ( (oral), hydrochlorothiazide (oral), metoprolol succinate (oral), Murodipine (oral), Norvasc (oral), Toprol XL (oral), B Enicar (oral), metoprolol tartrate (oral), losartan (oral), Lisinopril-hydrochlorothiazide (oral), clonidine HCl (oral), Dio van HCT (oral), Cozaar (oral), Propranolol (oral), Pironolactone (oral), Azor (oral), carvedilol (oral), Core g (oral), Benicar HCT (oral), Exforge (oral), Ava pro (oral), Lotrel (oral), verapamil (oral), furosemide (oral) (oral), Lasix (oral), Hyzaar (oral), Tekturna (oral), Enalapril maleate (oral), Micardis (oral), Losartan hydrochloride Lochlorothiazide (oral), Ramipril (oral), Lopressor (oral), Altace (oral), Micardis HCT (oral), Avalide (oral) (oral), diltiazem (oral), triamterene-hydrochlorothiazide (oral), Betalol (oral), terazosin (oral), amlodipine-benazepril (oral) , hydralazine (oral), Atacand (oral), benazepril (oral), Tr ibenzor (oral), triamterene (oral), doxazosin (oral), nif Edipine (oral), Ziac (oral), Aldactone (oral), Maxzi de (oral), Cartia XT (oral), Prazosin (oral), Cardiz em CD (oral), Zestril (oral), Dyazide (oral), Visop Lolor fumarate (oral), Tenex (oral), Tenormin (oral), Coreg CR (oral), Prinivil (oral), Valsartan (oral), Atenolol-chlorthalidone (oral), Edarbyclor (oral), benazep aryl-hydrochlorothiazide (oral), ferrous sulfate (oral), Ferrlecit ( Intravenous), Feraheme (intravenous), Feosol (oral), Infed (injectable) ), Integra (oral), Ferrex 150 Forte (oral), Tan dem Dual Action (oral), Ferrex 150 (oral), Gluco Ferrous phosphate (oral), Corvite 150 (oral), Integra F (oral) for oral use), NovaFerrum (oral use), iron (ferrous sulfate) (oral use), Vitron- C (oral), folic acid, corticosteroids, rituximab, IVIG, prednisone, Methylprednisolone (oral), Kenalog (injectable), Medrol (Pak) (oral), Medrol (oral), Dexamethasone (oral), Depo-Medr ol (for injection), prednisolone (for oral use), DexPak 13 Day (for oral use), Solu-Medrol (intravenous), hydrocortisone (oral), Cortef (oral) for oral use), Deltasone (oral use), triamcinolone acetonide (injection), corticosteroids steroids (oral), cholinesterase inhibitors (e.g., donepezil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne), memantine Nitin, Aricept, Namenda, Namenda XR, Razadyne ER, Alpha E, Vitamin E, Hydergine, Namzaric, Dopamine agonists (e.g., pramipexole (Mirapex), ropinirole (Requi p), rotigotine (Neupro (patch)) and apomorphine (Apokyn) etc.), anticholinergics (e.g., benztropine (Cogentin) and trihexif Ethylenediamine, etc.), MAO-B inhibitors (e.g., Eldepryl, Zelapar) and and rasagiline (Azilect), COMT inhibitors (e.g., entacapone (C omtan), carbidopa / levodopa (Sinemet®, etc.), amantadine tetrabenazine (Xenazine), haloperidol (Haldol), chlorpromazine romazine, risperidone (Risperdal), quetiapine (Seroquel), Olanzapine (Zyprexa), indomethacin, sulindac, etodolac, mefena meclofenamic acid, meclofenamic acid sodium, flufenamic acid, tolmetin, Ketorolac, diclofenac, diclofenac sodium, ibuprofen, naproxen phenoprofen, naproxen sodium, fenoprofen, ketoprofen, flurbiprofen , Oxaprozin, Piroxicam, Meloxicam, Ampiroxicam, Droxicam, Lor Noxiccam, cinnoxicam, sudoxicam am) and tenoxicam.

[0128] In addition, the fatty acid compounds disclosed herein may be used in combination with other pharmaceutical agents, such as androgens. hormones (e.g., erythropoietin), folic acid, vitamin B12, vitamin C, Citric acid, niacin, pyridoxine, riboflavin, biotin, thiamine, calcium formate Aminoxin, Anadrol-50, Chromagen Forte, Ep oetin alfa, Epogen, Fe C Tab Plus, FeRiva, F eRivaFA, Ferocon, Ferotrin, Ferrelet 90, Fer rex 28, Ferrogels Forte, FoliTab 500, Fumat inic, Hematogen Forte, Hemetab, Integra Plu s, Irospan 42 / 6, Lenalidomide, Maxaron Fort e, Myferon 150 Forte, MyKidz Iron, NovaFerr um, Oxymetholone, Procrit, Proferrin-Forte, Pyridoxine, Repliva 21 / 7, Revlimid and Trico n, etc.) can be administered. Iron acid, iron carbonyl, ferrous aspartoglycinate, heme iron polypeptide (which is sometimes may be indicated), and one or more drugs selected from ferrous bisglycinate It can be used in combination with an agent.

[0129] [dosage] As will be readily apparent to one skilled in the art, useful in vivo dosages to be administered, and The specific mode of administration will depend on the age, weight, severity of the condition, and the mammalian species to be treated. The specific forms of the various compounds used, as well as the specific The determination of an effective dosage level, i.e., the desired dosage, will vary depending on the use. Determination of the dosage level necessary to achieve the desired result can be accomplished using conventional methods, e.g., This can be accomplished by those skilled in the art using in vivo studies. the Maximum Safe Starting Dose in Initiation al Clinical Trials for Therapeutics in A dult Healthy Volunteers” (U.S. Food and Drug Administration, July 2005) The month may be referenced.

[0130] In some embodiments, the methods provided herein comprise administering to a subject a therapeutically effective amount of the present invention. This may include administering a composition provided herein. In this context, a therapeutically effective amount refers to modulation of markers of the conditions set forth herein, including inflammation. In some embodiments, a therapeutically effective amount may be determined by , which may be determined by reference to modulation of symptoms of the conditions set forth herein. In yet another embodiment, for the treatment of the conditions described herein, including inflammation, Various guidelines for the conditions described herein, including but not limited to: Various established guidelines may be referenced.

[0131] Dosages vary widely depending on the desired effect and therapeutic indication (e.g., marker levels, etc.). Alternatively, the dosage may vary as understood by one of skill in the art. , may be based on the patient's surface area or weight, and may be based on the patient's surface area or weight. The exact dosage will be determined on a case-by-case basis or may be calculated as follows: Daily Dosage for Adult Patients The plan is to use, for example, fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) or Oral doses of a plurality of fatty acids or salts or derivatives thereof The oral dose of the mixture is about 0.01 mg to about 10,000 mg, about 1 mg to about 5,000 mg , about 5 mg to about 2000 mg, about 10 mg to about 1000 mg, or about 50 mg to about 50 A single dose may be about 0.0 mg of a fatty acid or a salt or derivative thereof. 1mg, about 0.1mg, about 1mg, about 5mg, about 10mg, about 20mg, about 50mg, about 100mg, about 200mg, about 300mg, about 400mg, about 500mg, about 600mg , about 800mg, about 900mg, about 1000mg, about 2000mg, about 5000mg or The dosage may be adjusted according to the subject's weight, e.g. For example, dosages may be about 0.001 mg / kg, about 0.01 mg / kg, about 0.1 mg / kg , about 0.5mg / kg, about 1mg / kg, about 2mg / kg, about 3mg / kg, about 4mg / kg, approximately 5mg / kg, approximately 6mg / kg, approximately 7mg / kg, approximately 8mg / kg, approximately 9mg / kg, approx. 10mg / kg, approx. 15mg / kg, approx. 20mg / kg, approx. 25mg / kg, approx. Dosage may be as appropriate for each individual subject. As such, it may be a single dose, or two or more doses given over the course of one or more days. In some embodiments, the compound may be a continuous treatment. Over the course of treatment, for example, about 1 week or more (e.g., 1 week, 2 weeks, 3 weeks for several weeks (for 1, 4, 5, 6, 7, 8 or more weeks) It has been about a month or more (e.g., 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months or older) The drug may be administered over a period of about one or more years, or over a period of several years. In some embodiments, a fatty acid (e.g., an odd-chain fatty acid or a very long even-chain fatty acid) The dosage of steroids (e.g., steroids, steroid derivatives, etc.) or their salts or derivatives is once per day, twice per day, or once per day. It can be administered or taken in three or more doses.

[0132] As will be appreciated by those skilled in the art, in certain circumstances, the methods disclosed herein may be The compounds may be administered in amounts exceeding the preferred dosage ranges set forth above to effectively treat the subject. It may be necessary to administer the

[0133] Unit dosage forms configured for administration on a predetermined schedule are also provided (e.g., (e.g., individually packaged products containing a predetermined amount of the composition). Designed for administration one to three times per day. However, in certain embodiments, unit dosage forms are preferred. The dosage form may be administered for more than three times per day or for less than one time per day. It may be desirable to set up for faster administration.

[0134] Dosage and intervals are determined based on a predetermined parameter, index or marker value, or a minimum To provide plasma levels of the active moiety that are sufficient to maintain the effective concentration (MEC) may be adjusted to the individual subject as needed to achieve the desired result. The dosage to be administered will depend on individual characteristics and the route of administration. For example, an HPLC assay or bioassay can be used to determine serum concentrations. It may be used for.

[0135] In some embodiments, the compounds and methods provided herein are useful for, e.g., U.S. Patent No. 7,651,845, U.S. Patent No. 8,251,904, U.S. Patent No. 8,2 No. 51,904, U.S. Pat. No. 4,985,015, U.S. Pat. No. 8,827,957, U.S. Patent No. 4,252,159, U.S. Patent No. 5,318,521, U.S. Patent No. 4,7 18,430, U.S. Patent Application Publication No. 2011 / 0190702, German Patent DE2 615061, and using such a device. In conjunction with the method, also described, for example, in U.S. Patent Application Publication No. 2012 / 0072236 It may be used in conjunction with a diagnostic device as provided.

[0136] [Diagnostics and Monitoring] The present invention provides methods for diagnosing and monitoring various conditions, including inflammation, as set forth herein. A method for coding is provided.

[0137] In some embodiments, the diagnostic or monitoring method comprises measuring the amount of fat in a body fluid. In some cases, the method further comprises measuring the proportion of fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids). In some embodiments, the diagnostic or monitoring method involves inflammation. The method may also include measuring in the subject a marker for the condition as set forth herein. In some embodiments, the diagnostic or monitoring method comprises determining whether anemia of chronic disease is present. In some embodiments, measuring one marker Correlation of the car with other markers may prove useful. In this condition, inflammation or related conditions are identified by reference to a threshold level of erythrocyte sedimentation rate. For example, or threshold levels of serum odd-chain fatty acids or serum very long even-chain fatty acids. In some embodiments, inflammation may be diagnosed by examining the The conditions set forth herein, including those listed above, are defined by reference to threshold levels of markers for the condition. Therefore, for example, the proportion of odd-chain fatty acids in serum, the serum concentration of odd-chain fatty acids, and the total odd-chain fatty acids in serum serum very-long even-chain fatty acids, serum total very-long even-chain fatty acids, or two Diagnosis may be made by looking at threshold levels of ratios between serum fatty acids For example, threshold values may be set to refer to symptoms or markers of conditions set forth herein, including inflammation. For example, the condition may be metabolic syndrome. It is possible.

[0138] the proportion of fatty acids (e.g., odd-chain fatty acids or very long even-chain fatty acids) in the subject; Alternatively, markers of conditions described herein, including inflammation, may be obtained by any means. The sample for analysis may be any body fluid or tissue of the subject. It may originate from tissues such as serum, plasma, red blood cell membranes, urine, and feces. There may be cases where this occurs. [Example]

[0139] Example 1 Dolphins in the Navy Marine Mammal Program (MMP) are at increased risk of metabolic syndrome and Well-studied in various chronic diseases and diseases of aging, including iron metabolism disorders This population of dolphins is particularly susceptible to inflammation with age (V enn-Watson S, Smith CR, Gomez F, Jensen ED( 2011), Physiology of aging among healthy, older bottlenose dolphins(Tursiops trunc) atus):comparisons with aging humans, J Co mp Phys B, 181:667-680). MMP dolphins are Compared to wild dolphins living in the Bay of Tunisia, the dolphins had lower rates of metabolic syndrome and insulin resistance. and greater susceptibility to iron storage disorders (Venn-Watson et al., 2016 ), Increased dietary intake of saturated fatty acid heptadecanoic acid(C17:0) ass associated with decreasing ferritin and all eviated metabolic syndrome in dolphins, P (See LOS ONE, 10(7):e0132117.) MMP dolphins also Compared to Sarasota Bay dolphins, they had lower serum total odd-chain saturated fatty acid levels and Lower levels of even-chain saturated fatty acids (Table 1). Proposal for inflammation in MMP dolphins Possible risk factors include old age, chronic disease, and diet. Differences in forage fish (and Differences in certain fatty acids associated with certain types of fish may be responsible for the risk of inflammation. It can be assumed.

[0140] In this study, the effects on inflammation were assessed by comparing the fatty acid profile of 20 MMP dolphins ("A These dolphins were studied by changing their diet. These 20 Group A dolphins lived in a net pen in Diego Bay. 75% capelin (plus squid, herring or salmon) while maintaining From the standard diet of 25% capelin, 50% mullet, and squid, The diet consisted of a 25% mixture of herring or mackerel. Group A dolphins get one-third of their daily food in the morning after their daily overnight fast. During and 2 hours after the meal, trained blood samples were taken in water. (Typically around 10:00 AM). Ten more MMP dolphins ("Group B dolphins") They were maintained on the standard capelin diet throughout the study period. There were no differences in age, sex, or weight when compared (Table 2).

[0141] Capelin, the main reference species given to MMP dolphins, is C17: 0 was not detected (less than 0.007g / 100g). The main fish species given had 67 mg / 100 g of C17:0. C17:0 was measured as follows: herring = 19 mg / 100 g, and mackerel = 19 mg / 100 g. = 22 mg / 100 g. C17:0 was not detected in squid (Venn-Watso n et al. (2016), Increased dietary intake of sat urated fatty acid heptadecanoic acid(C17 :0) associated with decreasing ferritin and alleviated metabolic syndrome in dol phins, PLOS ONE, 10(7):e0132117 (see also).

[0142] Comparison of the daily intake of fatty acids from the standard and modified diets of dolphins shows that the intake of odd-chain saturated fatty acids Increased C17:0 intake from an average of 300 mg to 1,100 mg daily (approximately 4-fold increase), and an average daily intake of 1,300 mg of odd-chain saturated fatty acid C15:0 It was revealed that the average daily intake of 100mg of cereals containing ... The average daily intake of very long even-chain saturated fatty acid C24:0 increased from 0 mg to 30 mg (Table 3). Assuming an approximate average weight for the study dolphins of 159 kg, the dietary changes gave an approximate daily oral dose of C15:0 of 28 mg / kg body weight. The approximate daily oral dose after the change of 17:0 was 7 mg / kg body weight. The approximate daily oral dose after the change was 1.9 mg / kg body weight. There were no changes in total fat intake, C18:0, or C22:0 when compared. Daily intake of even-chain fatty acids (C14:0, C16:0, and C20:0), as well as Daily intakes of total omega-3 fat, total polyunsaturated fat, and total saturated fat were reduced in the modified diet. Ta.

[0143] Samples taken 2 hours after eating were collected from Group A and Group B dolphins at baseline (month 0). and at three time points after switching to the modified diet: 1 month, 3 months Dolphins were examined for serum fatty acid concentrations (total and various forms) at 12 months and 6 months. and assessed for indicators of inflammation (including erythrocyte sedimentation rate and alkaline phosphatase) did.

[0144] Serum fatty acid concentrations (including odd-chain saturated fatty acids and very long even-chain saturated fatty acids), as well as The changes in erythrocyte sedimentation rate and alkaline phosphatase were measured at 1 month, 3 months, and The comparison was performed in the study dolphins during the first and sixth months of the study, and repeated measures ANOVA was performed. The results were compared with the first month of use. Markers of anemia in Group A and Group B dolphins The results are shown in Table 4. The erythrocyte sedimentation rate of Group A dolphins increased by one month. The alkaline phosphatase activity in Group A dolphins decreased at 3 months. These changes were absent in Group B dolphins. Individual Group A dolphins with high erythrocyte sedimentation rates showed signs of inflammation resolving while on the modified diet. It is clear from Figures 1A and 1B that this was occurring.

[0145] A modified diet containing 50% mullet was given to 20 Group A dolphins for six months. (This will reduce the average daily dietary intake of C17:0 from 300mg to 1100mg.) g, and the average daily intake of C15:0 was increased from 1,300 mg to 4,500 m g), serum total odd-chain saturated fatty acid concentrations increased significantly at 1 month compared to 0 months. The serum concentrations increased by 1 day and were maintained throughout the 6-month period (Table 5). Specifically, at 1 month, serum total C15:0 concentration increased to 94±33uM, and blood The total C17:0 concentration in the supernatant increased to 82±21 uM. In addition, many odd-chain saturated fatty acids Increased concentrations of the form were observed among Group A dolphins throughout the diet change period compared to month 0. These include elevated C15:0 and C17:0 neutral fatty acids (e.g., e.g., triacylglycerides) and elevated C15:0 phospholipids and C17:0 phospholipids. Lipids (e.g., phosphatidylcholine and lysophosphatidylcholine) were included (Table 6) These changes in the various forms of odd-chain saturated fatty acids were not present in the control dolphins of Group B. Therefore, the effect of C15:0 at 28 mg / kg body weight or C15:0 at 7 mg / kg body weight was not observed. Approximately daily oral doses of C17:0 significantly increased the effects of these odd-chain saturated fatty acids on May be used to achieve elevated concentrations.

[0146] A modified diet containing 50% mullet was given to 20 Group A dolphins for six months. The total serum concentration of C26:0 (very long even-chain saturated fatty acids) was significantly increased at 1 month compared to 0 months. The serum concentrations increased by 1 day and were maintained throughout the 6-month period (Table 5). Additionally, increased concentrations of numerous additional very long even-chain saturated fatty acid forms were observed compared to month 0. , was observed in Group A dolphins throughout the diet change period, including elevated serum 22 :0 ceramide and 22:0 hexosylceramide concentrations, as well as elevated C24: 0 ceramide concentration, C24:0 dihydroceramide concentration and C24:0 hexosylceramide concentration These changes in the various forms of very long even-chain saturated fatty acids were Even-chain saturated fatty acids (C16:0 and C18:0) were absent in the control dolphins. However, neither change nor decline occurred among Group A dolphins while they were receiving the modified diet. Therefore, a daily oral dose of 1.9 mg / kg body weight of C24:0 is approximately the recommended dose for very long-term gestation. It may be used to achieve elevated concentrations of high chain saturated fatty acids.

[0147] Increased serum concentrations of odd-chain saturated fatty acids in Group A dolphins on the altered diet were associated with decreased red blood cell counts. C15:0 cholesterol was an independent linear predictor of hemoglobin sedimentation rate (Table 7). Increased serum concentrations of sterol esters and C17:0 phosphatidylcholine , independently predicted a lower erythrocyte sedimentation rate. Figures 2A-2B show that a lower erythrocyte sedimentation rate A direct correlation was found between the elevated levels of these odd-chain saturated fatty acid forms and the rate of decline. These figures also reveal a threshold effect; i.e., above 60 uM Serum cholesterol ester C15:0 concentrations greater than or equal to 30 uM By achieving a phosphatidylcholine C17:0 concentration of less than 15 mm / hr, Therefore, the serum concentration of odd-chain saturated fatty acids was compared with that of odd-chain saturated fatty acids. Increased daily oral intake of saturated fatty acids may improve inflammation As shown in Figures 2A and 2B, serum cholesterol levels exceeding 60 μM were significantly higher than those of the control group. Stereo C15:0 concentrations or serum phosphatidylcholine C17 levels greater than 30 uM By using the proposed therapeutic threshold of 0:0 concentration, a lower erythrocyte sedimentation rate is also It may be maintained.

[0148] Increased serum concentrations of very long even-chain saturated fatty acids in Group A dolphins on modified diets were improved. were independent linear predictors of the observed red blood cell indices (i.e., anemia) (Table 7). In particular, increased concentrations of C20:0 and C22:0 hexosylceramide forms result in better Figures 3A-3B show that a decreased erythrocyte sedimentation rate was independently predicted by erythrocyte sedimentation rate (ESR). revealed a linear association between consuming large amounts of saturated fatty acids and increased levels of these very long even-chain fatty acid forms. These figures also reveal a threshold effect; i.e., above 0.20 μM Serum hexosylceramide C20:0 concentrations exceeding 0.11 uM or serum hexosylceramide C20:0 concentrations exceeding 0.11 uM Achieving hexosylceramide C22:0 concentrations below 15mm / hr This resulted in an increase in the sedimentation rate, thus increasing the serum concentration of very long even-chain saturated fatty acids. This can improve red blood cell indices and alleviate anemia. As shown in Figures 3A-3B, serum hexosylceramide C2 levels exceed 0.20 μM. 0:0 concentration or serum hexosylceramide C22:0 concentration greater than 0.11 uM By using the proposed therapeutic threshold of , a lower erythrocyte sedimentation rate is also maintained. This may be the case.

[0149] Increased serum concentrations of odd-chain saturated fatty acids are an independent predictor of improving anemia increased serum very-long even-chain saturated fatty acids is an independent predictor of improving anemia As shown in Figures 4A to 4D, the C15:0 cholesterol concentration was significantly higher than that of the control group. The increasing serum concentrations of ester forms of steroids are due to the C22:0 and C24:0 hexosylation. There was a positive association with increasing serum concentrations of the C17:0 phosphatidylcholinesteramide form. Increasing serum concentrations of glycerol forms are due to the C22:0 and C24:0 hexosylceramides. The results showed that the association of odd-chain saturated fatty acids with increasing serum concentrations of the α- and β-blockers was positively associated with increased serum concentrations of the α- and β-blockers. Increased serum concentrations of various odd-chain saturated fatty acid forms as a result of daily oral intake also This is accompanied by an increase in serum concentrations of various targeted very long even-chain fatty acid forms.

[0150] Figure 5 summarizes the results from the dolphin study, including: 1) odd numbers Increased oral intake of odd-chain saturated fatty acids increases the intake of total odd-chain saturated fatty acids and various odd-chain saturated fatty acid forms. 2) Increased oral intake of very long even-chain saturated fatty acids results in increased serum concentrations of 3) increased serum concentrations of various very long even-chain saturated fatty acid forms; The increased serum concentrations of odd-chain saturated fatty acids due to oral intake of saturated fatty acids include various very long-chain saturated fatty acids. and 4) increased serum concentrations of odd-chain saturated fatty acids or extra- Increased serum concentrations of long even-chain saturated fatty acids result in a linear decrease in the erythrocyte sedimentation rate and independently predicted attenuated inflammation.

[0151] [Sample collection and transportation] The blood was then transferred to a BD Vacutainer serum separator (for serum fatty acid profiling). The serum was collected in a vacuum tube containing EDTA (K3). The tubes were centrifuged at 3000 rpm for 10 minutes within 30 to 60 minutes of collection and then transported. The serum was transferred to cryovials and shipped via overnight courier to a reference laboratory. The samples were stored at -80°C until shipped on dry ice.

[0152] [Sample Analysis] Total serum fatty acid profile was obtained from the Kennedy Krieger Institute The study was conducted by Genetics Laboratories in the United States. An AT-Silar-100 column (Grace, Columbia, NY) was used as described in Pentafluorobenzyl bromide fatty acid derivatization using (Maryland 21044) The samples were analyzed by capillary gas chromatography / mass spectrometry. The data were required to pass clinical laboratory quality control before publication. CV% The percent fatty acids in serum were typically less than 10%. was used as a more robust indicator to help reduce potential variability in

[0153] Determination of serum fatty acid concentrations, including various fatty acid classes, using complex lipidomics , Metabolon, Inc. (Durham, North Carolina) Lipids were analyzed by dichloromethane and methanol in the presence of an internal standard. The lower organic phase was extracted from the sample using a Bligh-Dyer extraction The extract was concentrated under nitrogen and diluted with 10 mM ammonium acetate. Reconstituted in 0.25 mL of dichloromethane:methanol (50:50). Extract Place the sample in a vial for injection-MS analysis and perform MS analysis in both positive and negative modes. Sciex 5500QTR with SelexION using electrospray Each sample was analyzed twice, with the monitor The analysis was performed using IMS-MS conditions optimized for the lipid class being monitored. QTRAP was used to monitor the evolution of over 1,100 lipids from up to 14 lipid classes. The system was run in MRM mode to monitor individual lipid species at known concentrations. Based on the ratio of the signal intensity for the target compound to the signal intensity for the internal standard The concentration of a lipid class was calculated from the sum of all molecular species within the class, and fatty acids The composition was determined by calculating the proportion of individual fatty acids within each class. Ta.

[0154] The fatty acid profile of fish was analyzed by Covance Laboratories (Madiso The study was conducted by the University of Wisconsin 53703. Each of the following fish species was tested in water and Mixed and homogenized for uniformity: Canadian and Icelandic carafes Capelin (Mallotus villosus), herring (Clupea hare ngus), mackerel (Scomber japonicus), squid (Loligo op alescens) and striped mullet (Mugil cep Lipids were extracted and saponified with 0.5N methanolic sodium hydroxide. The resulting methyl esters of fatty acids were converted to hydroxybenzoates. The lipids were extracted with ethanol. An internal standard was added before lipid extraction. The methyl esters of fatty acids were The compounds were analyzed by gas chromatography using external standards for quantification. Using the data from the previous study, the total daily intake of each fatty acid for each study dolphin was calculated. The amounts were compared between 1) the reference diet before the study and 2) the modified diet (Group A) or the reference diet during the study. (Group B) was calculated based on records of food consumed by fish species.

[0155] To determine the erythrocyte sedimentation rate (ESR) from 1 ml of whole blood containing EDTA over a 60-minute period, a commercially available The blood sedimentation system (related to the Westerngren method) was used. In the laboratory, Olympus AU600 (Olympus America, Ce The 1000-kilometer (McGraw-Hill, Pennsylvania) was used.

[0156] Statistical analysis was performed using the World Programming System software ( World Programming Ltd., Hampshire, UK) Significance was defined as a P value of 0.05 or less. Mean dietary intake was calculated for Group A and Group B dolphins using the Wilcoxon rank sum test. Comparisons were made between the pre-study diet and the study diet. Obtained red blood cell index values (hematocrit, packed cell volume, hemoglobin, and red blood cell count) and serum fatty acid concentrations (total and individual types) were analyzed using repeated measures ANOVA (mixed models). The dolphins in groups A and B were compared at month 0 using the ELISA kit. Fatty acids with concentrations in the modified diet but not in the control were included in the stepwise regression model (e.g. , C17:0 total, triacylglyceride form, phosphatidylcholine form, lysophosphatidylcholine Phosphatidylcholine forms, phosphatidylethanolamine forms and lysophosphatidylethanolamine forms (including the ethanolamine form in one model), and which form is responsible for the hematocrit, blood cell volume, and We then investigated whether erythrocyte count (RBC) was an independent predictor of hemoglobin or red blood cell count (RBC). Fatty acids, which are independent predictors of the indices, were compared linearly with the red blood cell indices using simple linear regression. The linear relationship was verified. It is an independent predictor of red blood cell indices and (<0.05) P value and R of 0.1 or greater 2 have a positive linear association with these indices (defined as The fatty acids present in the diet were characterized as fatty acids that independently predict improved inflammation.

[0157] Table 1 shows the numbers of dolphins in the Navy Marine Mammal Program (MMP) and wild dolphins in Sarasota Bay. Between and, red blood cell indices, serum total odd-chain fatty acids (% of total fatty acids), and serum A comparison of total very long even-chain fatty acids (% of total fatty acids) is shown. [Table 1]

[0158] Table 2 shows the results for Group A dolphins placed on the modified fish diet and Group B dolphins maintained on the baseline diet. A demographic comparison with Luke is provided. [Table 2]

[0159] Table 3 shows the total daily nutrient intake between the standard diet and the test diet for each group. A comparison of the quantities is shown. [Table 3]

[0160] Table 4 shows the relationship between Group A case dolphins on the modified diet and Group B control dolphins on the baseline diet. A comparison of inflammatory indicators in the [Table 4]

[0161] Table 5 shows the relationship between the Group A case dolphins on the modified diet and the Group B control dolphins on the baseline diet. A comparison of total serum fatty acid concentrations in the following groups is shown. [Table 5]

[0162] Table 6 shows that the change in diet from month 0 in the case dolphins of Group A was significant (P ≤ 0.0 5) Comparison of serum concentrations of various fatty acid forms is shown. These changes were compared with baseline. It was not present in the group B control dolphins on diet (data not shown). [Table 6]

[0163] Table 7 shows the independent effect of the decreased erythrocyte sedimentation rate in Group A dolphins while on the modified diet. Serum fatty acids that were linear predictors are shown. [Table 7]

[0164] Increased serum concentrations of odd-chain saturated fatty acids and very long even-chain saturated fatty acids independently increased the erythrocyte sedimentation rate. Severity and alkaline phosphatase are two-factor linear predictors of inflammation. increased the intake of odd-chain saturated fatty acids and very long even-chain saturated fatty acids by changing the fish feed species. In this case, the erythrocyte sedimentation rate and alkaline phosphatase levels decrease, which reduces inflammation. This suggests that deficiencies in odd-chain saturated fatty acids and very long even-chain saturated fatty acids may contribute to inflammation and oxidative stress in humans. This may be a treatable cause behind the chronic diseases that result from it. Dolphins and humans have large brains and similar diseases, including abnormal metabolism and age-related conditions. This may be because dolphins are a long-lived species in which the disease occurs. It provides a valuable animal model.

[0165] Several similarities have been identified between dolphins and humans, e.g. Dolphins have a long lifespan. The average lifespan of a dolphin is 20 years in the wild, but 32 years in the MMP. The long lifespan of dolphins and humans is about 60 years. This has led to improved knowledge of chronic and age-related diseases in humans, including chronic anemia. In addition, dolphins and humans have large brains. Among mammals, humans have the largest (EQ=7.4) (brain-to-body ratio is the ratio of brain-to-body ratio for a given species' body size. (Defined as actual brain size relative to predicted brain size). The bottlenose dolphin has a higher EQ than the chimpanzee (EQ=2.4), while the bottlenose dolphin has a higher EQ than the chimpanzee (EQ=5.3). It is larger than that of a mouse (EQ=0.5) and is much larger than that of a living Positron emission tomography of dolphins has revealed high levels of glucose consumption in the dolphin brain. Thus, the large brain size, combined with the high glucose requirement, is a common trait shared by humans and dolphins. This is thought to be a factor in the development of glucose metabolism and related physical conditions.

[0166] Dolphins and humans share similar genetic adaptations as well as glucose metabolism. Adult dolphins have a glucose transport system that uses the GLUT-1 transporter isoform. Blood cells have a high capacity for glucose transport; prior to this discovery, this capacity was limited to primates. Common red blood cell glucose levels in cetaceans and primates The transport system is thought to be responsible for the large glucose demands of the central nervous system. The genome of Luca was developed by Baylor University based on a dolphin from the U.S. Navy Marine Mammal Program. Dolphins are among the longest-lived and largest-brained species (including humans). They have genetic evolutionary adaptations that are unique to mammals (including cats and elephants). The mice have similar genes involved in glucose metabolism (Office of Naval Research-sponsored research, unpublished data). Therefore, dolphins may be a potential risk factor for human inflammation, metabolic syndrome, hyperferritinemia, and and an appropriate model of the conditions that accompany them.

[0167] [Dolphins and humans suffer from similar diseases and disease complications] Like humans, common bottlenose dolphins (Tursiops truncatus) Similar to the increase in haptoglobin levels associated with high glucose, the erythrocyte sedimentation rate and alkaline phosphatase Inflammation may develop, including elevated levels of phospholipase A (PGA) and elevated levels of ceruloplasmin. A Navy Marine Mammal Program dolphin in Diego Bay, California is a metabolically well-studied population, and this group is located in Sarasota Bay, Florida. Lower hematocrit and hemoglobin levels compared to wild-caught bottlenose dolphin populations Importantly, there are also implications for metabolic syndrome and inflammation. The existence of Luke's case and reference populations represents a similar comparison of human populations.

[0168] Like humans, dolphins can develop nonalcoholic fatty liver disease (NAFLD). AFLD has been found in both wild-caught and managed-caught dolphins, and This suggests that dolphins have a general physiological susceptibility to metabolic syndrome. NAFLD is associated with inflammation in humans and dolphins, and NAFLD is associated with liver damage. These events, accompanied by long-term low-level inflammation in both species, progress to liver inflammation and cirrhosis. Progression of metabolic disorders is accompanied by insulin resistance and worsening glucose control.

[0169] Like humans, dolphins suffer from a chronic condition involving high ferritin (hyperferritinemia) and iron. In humans and dolphins, the disease is primarily caused by an accumulation of erythropoietin in the Kupffer cells of the liver. Excessive iron deposition due to age-related progression and inflammation, elevated lipids, insulin and liver function. This metabolic state in dolphins involves the presence of either a mutation in the HFE gene. There is no mutation of

[0170] Dolphins develop age-related blood changes similar to those seen in humans as they age. Specifically, Absolute lymphocyte, serum globulin, and mean platelet volume decrease with age (= age 30 years and older) Increases linearly with age (up to age 50). Mean white blood cells, neutrophils, serum globulin, red blood cells Hemocyte sedimentation rate, serum cholesterol and triglycerides, and neutrophilia The prevalence of hyperglobulinemia and hypercholesterolemia increases as geriatric dolphins age. In this study, the elderly dolphins showed signs of aging, including the appearance of inflammation. with changes in hematology and serum chemistry values similar to those found in humans As such, bottlenose dolphins are thought to be a model for the aging process in humans. It can serve as a useful comparative model for

[0171] For these reasons, dolphins and humans are important and relevant candidates for various human diseases, including inflammation. The anatomy, physiology, and disease states support dolphins as a valid animal model. Both share important common ground. The results cited herein for dolphins also , may be beneficial for humans.

[0172] Example 2 In humans, obesity, aging, cardiometabolic disease, and dementia (including Alzheimer's disease) These include adipokines (cytokines), interleukin 6 (IL-6), interleukin 1 (IL-1), and including elevated levels of interleukin-18 (IL-18) and monocyte chemoattractant protein-1 (MCP-1) and inflammation (see accompanying references, Targher et al.). Following the results from Example 1 Oral administration of synthetic odd-chain saturated fatty acids has been shown to reduce inflammation in conventional laboratory animal models. It can be assumed that this will reduce

[0173] This study investigated the effects of daily oral administration of synthetic pentadecanoic acid (C15:0) on inflammation. This was investigated in an obese mouse model. Twenty C57BL / 6J mice were fed a high-fat diet (HF) D) (D12492, 60% of the calories were from fat) was given for 8 weeks. Study mice were divided into two groups of 10: vehicle control and C15:0-treated. The predicted therapeutic dose of 5 mg / kg was determined based on the variability in the dolphin model. The test product was a synthetic powder form that was stable at room temperature and was a-Purchased from Aldrich (product W433400 (>99% C15:0)). The test product was administered by gavage for 12 weeks (84 days) while continuing to feed HFD ad libitum. The mice were fed daily by gavage. Body weight and food intake were measured weekly. IL-6, IL-18 Serum levels of β-lactamase (MCP-1) and β-lactamase (MCP-1) were measured on day 84. Data from treatment groups were compared. Comparisons with the control group were performed using Coxson rank sum analysis. Significance was determined as a P value of 0.05 or less. Defined.

[0174] Mice in the C15:0 treatment group tolerated the test article throughout the study. None occurred among mice in the control group; one mouse in the control group died at 7 weeks. Changes were not observed when comparing study groups in terms of body weight, percent body weight change, or diet. No effect was found on food intake (not shown).

[0175] When the C15:0-treated group was compared with the vehicle control group, C15:0 (5 mg / kg) Subjects treated with α-glucan showed lower inflammation and lower adipokines compared to controls. (IL-6, IL-18, and MCP-1) (Table 8, Figures 6A to 6C).

[0176] Table 8 shows the results of the 84-day treatment of obese mice with oral synthetic C15:0 versus vehicle. Comparison of serum adipokine (cytokine) levels with controls is shown. [Table 8]

[0177] Odd-chain fatty acids (heptadecanoic acid or C17:0 and pentadecanoic acid or C1 Odd-chain saturated fatty acids (O5:0) are saturated fatty acids present in whole-fat ruminant dairy products. It is assembled by bacteria in the rumen and passes from the rumen into milk. When examined, odd-chain saturated fatty acids were highest in butter and full-fat yogurt, It was not present in non-fat dairy products. Interestingly, consumer trends away from high-fat foods Nevertheless, dairy consumption in humans is associated with lower markers of inflammation and insulin including a lower risk of resistance syndrome, metabolic syndrome, and type 2 diabetes To date, the effects of dairy on inflammation and metabolism in humans have been poorly documented. The mechanisms of the various benefits have not been elucidated. In this context, odd-chain saturated fatty acids play an important role in the anti-inflammatory benefits of dairy products in humans. It can be suggested that this may be the case.

[0178] To take advantage of these benefits, odd-chain saturated fatty acids are available in tablets, capsules, and gels. in any form, including as a cap pill, liquid suspension, spray or powder Supplements, food additives, food fortifiers, beverage additives, beverage fortifiers or It can be used in pharmaceuticals and in human and animal samples (including is the proportion of odd-chain saturated lipids in blood (including serum, plasma, and red blood cell membranes), urine, and feces. Various diagnostic tests and assays for fatty acids are used to detect low odd-chain saturated fatty acids. and odd-chain saturated fatty acid levels can be monitored continuously in patients. The use of odd-chain saturated fatty acids can reduce: 1) elevated erythrocyte sedimentation rate, inflammation, and biomarkers of various associated complications (including anemia of chronic disease, insulin resistance, Antibiotics, metabolic syndrome, hypertension, diabetes, non-alcoholic fatty liver disease, heart Vascular diseases, cancer, various diseases of aging, neurodegenerative diseases (Alzheimer's disease and other forms of to achieve the prevention, control and treatment of dementia (including dementia) and other related conditions These serious health effects can not only be prevented in dolphins, However, due to the similarity in blood panels, it can be similarly prevented in human mammals.

[0179] These data support the role of odd-chain saturated fatty acids in attenuating inflammation in feeding studies. The direct effects of odd-chain saturated fatty acids and very long even-chain saturated fatty acids were This suggests that fish richer in even-chain saturated fatty acids may be involved. The potential effects (or cumulative effects) of other nutrients on serum ferritin remain unclear. 1) Higher concentrations of odd-chain saturated fatty acids and very long even-chain saturated fatty acids are associated with lower 2) be confirmed as an independent predictor of erythrocyte sedimentation rate during the feeding study; demonstrated increased dietary intake of odd-chain saturated fatty acids and very long even-chain saturated fatty acids and 3) the erythrocyte sedimentation rate and and alkaline phosphatase, and the effects of odd-chain saturated fatty acids and very long even-chain saturated fatty acids It was confirmed that the increase in serum fatty acid concentrations was coincident with the increase by one month. Therefore, increasing the dietary odd-chain saturated fatty acids and very long even-chain saturated fatty acids reduced Evidence was provided that erythrocyte sedimentation rate and alkaline phosphatase were contributing factors. This suggests that odd-chain saturated fatty acids and very long even-chain saturated fatty acids are equally effective in treating inflammation. Similarly, it has been shown that the compound may also be used to treat other concomitant or related conditions. do.

[0180] Investigate the risk or cause of inflammation in the absence of odd-chain saturated fatty acids and very long even-chain saturated fatty acids. It can be used to extract saturated fatty acids containing odd-numbered chains and very long even-numbered chains. Dietary supplements, including cereals containing gluten, may be helpful in resolving inflammation and associated conditions.

[0181] The following materials are incorporated herein by reference in their entirety: Colegrove K. (2015) Histomorphology of the bottlenos e dolphin (Tursiops truncatus) pancreas and association of increasing islet β-ce ll size with chronic hypercholesterolemi a. J Gen Comp Endocrinol 14:17-23; Venn- Watson (2012) Hemochromatosis and fatty change: building evidence for insulin re sistance in bottlenose dolphins (Tursiop s truncatus). J Zoo Wildlf Med 43:S35-47 ; Venn-Watson S. (2007) Big brain and bl ood glucose: Common ground for diabetes mellitus in humans and healthy dolphins. Comp Med 57:390-5; Venn-Watson S. (2013 ) Blood-Based Indicators of Insulin Resi stance and Metabolic Syndrome in Bottlen ose Dolphins (Tursiops truncatus). Front Endocrinol (Lausanne) 4:136; Venn-Watso n S. (2011) Dolphins as animal models fo r type 2 diabetes; Sustained, postprandi al hyperglycemia and hyperinsulinemia. G en Comp Endocrin 170:193-9; Venn-Watson S. (2014) Dolphins and Diabetes: Applyin g One Health for breakthrough discoverie s. Front Endocrinol DOI 10.3389 / fendo.20 14.00227; Venn-Watson S. (2015) Increase d dietary intake of saturated fatty acid heptadecanoic acid (C17:0) associated w ith decreasing ferritin and alleviated m etabolic syndrome in dolphins. PLOS ONE 10:e0132117. Sonolesky PM, Harrel T, Par ry C, Venn-Watson S, Janech MG (2016) Fe eding a modified diet to bottlenose dolp hins leads to an increase in serum adipo nectin and sphingolipids consistent with improved insulin sensitivity, Front End ocrinol 7:33; Venn Watson S, Carlin K, A ndrews GA, Chavey PS, Mazzaro L (2013) A ssociations of ceruloplasmin and hepatog robin with inflammation and glucose in b ottlenose dolphins (Tursiops truncatus)J Comp Clin Path DOI: 10.1007 / s00580-013- 1738-0. Venn-Watson S, Smith CR, Gomez F , Jensen ED (2011) Physiology of aging a mong healthy, older bottlenose dolphins (Tursiops truncatus): comparisons with a ging humans. J Comp Phys B 181:667-680.

[0182] Methods and compositions related to or applicable to inflammation or related conditions are described in the following references: and the like, which are incorporated herein by reference in their entireties: Blood 88:3608-3614; Zandman-Goddard G, Shoenf eld Y (2008) Hyperferrinemia in autoimmune IMAJ 10: 83-84; Zandman-Goddard G, Shoenfeld Y (2008) Ferritin in autoimmune ne diseases. Autoimmunity Rev 6:457-463; Hodson, L, Skeaff CM, Fielding BA. (200 8) A review of even-chain fatty acid met abolism and the role of arachidic acid ( C20:0) and lignoceric acid (C24:0) in he alth and disease, The Lipid Handbook, 60 5-633; Yin G. (2015) Pfeuffer M, Jaudszu s A, Pentadecanoic and Heptadecanoic Aci ds: Multifacted Odd-Chain Fatty Acids, A dv Nutr. 2016 Jul 15;7(4):730-4; Fave,G. 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(2010) Fatty acids measured in plasma and erythrocyte-membrane phosp holipids and derived by food-frequency q uestionnaire and the risk of new-onset t ype 2 diabetes: a pilot study in the Eur opean Prospective Investigation into Can cer and Nutrition (EPIC)-Norfork cohort. Am J Clin Nutrition 92:1214-22; Krachle r B. (2008) Fatty acid Nutrition, metabo lism, and cardiovascular diseases. NMCD 18;503-10; Maruyama C. (2008) Difference s in serum phospholipid fatty acid compo sitions and estimated desaturase activit ies between Japanese men with and withou t metabolic syndrome. J Atherscler Throm b 15:306-313; Choi H. (2005) Dairy comsu mption and risk of type 2 diabetes melli tus in men: a prospective study. JAMA In ternal Med 165:997-1003; Krats M. (2014) Dairy fat intake is not beta-cell funct ion in humans. The American journal of c linical nutrition. 99:1385-96; Mennen L. (2000) Possible prospective effect of b read and dairy products on the risk of t he metabolic syndrome. 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Alterations in Nutrition, Ketosis and Inflammation in peripartal Holstein Cows. PLoS One 10 , e0139963. doi: 10.1371 / journal.pone.01 39963; Annual, seasonal and individual v ariation in hematology and clinical bloo d chemistry profiles in bottlenose dolph ins (Turisiops truncatus) from Sarasota Bay, Florida. Comp Biochem Physiol A Mol Integr Physiol 148, 266-277.doi: 10.101 6 / jcbpa.2007.04.017; Hannun, Y,A,, (2008 ). Principles of bioactive lipid signall ing: lessons from sphingolipids. Nat Rev Mol Cell Biol 9, 139-150. doi: 10.1038 / nrm2329; Hassanali, Z.. (2010). Dietary supplementation of n-3 PUFA reduces wegh t gain and improves postprandial lipaemi a and the associated inflammatory respon se in the obese JCR:LA-cp rat. Dabetes O bes Metab 12, 139-147. doi: 10.1111 / j.14 63-1326.2009.01130.x; Profenno LA, Porst ensson AP, Faraone SV (2010) Meta-analys is of Alzheimer’s disease risk with obes ity, diabetes and related disorders. 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[0183] The above description describes the best mode contemplated for carrying out the invention, as well as the method for creating the invention. The manner and process of producing and using the invention will be apparent to anyone skilled in the art to which the invention pertains. A clear, concise and easy-to-understand statement that will enable anyone to make and use the invention. However, the present invention is presented in more precise terms than the best mode discussed above. Accept a variety of modifications and alternative assemblies that are sufficiently equivalent Therefore, the invention is not limited to the particular embodiments disclosed. Rather, the invention is defined by the following claims particularly pointing out and distinctly claiming the subject matter of the invention. All modifications and variations that fall within the spirit and scope of the present invention as generally expressed by the following paragraphs are intended to be included herein. The disclosure is illustrated in the drawings and foregoing description, and includes alternative constructions. Although specifically described, such illustrations and descriptions are illustrative and not restrictive. shall be considered exemplary.

[0184] All references cited herein are incorporated by reference in their entirety. Publications and patents or patent applications incorporated by reference are incorporated herein by reference. If any disclosure conflicts with the disclosure contained in this application, the present specification shall preclude any such conflict. It is intended to supersede and / or supersede.

[0185] Unless otherwise defined, all terms (including technical and scientific terms) Its ordinary and accustomed meaning to those skilled in the art must be given, and Unless expressly so defined in the Subdivision, no special or specially defined meaning shall be used. The use of particular terminology does not necessarily refer to certain features or aspects of the disclosure. When written, the term refers to any of the various features or aspects of the disclosure to which the term pertains. The term "compound" is intended to be redefined herein as limited to include such specific characteristics. It should be noted that this should not be interpreted as implying that The terms and phrases used in the application, and variations thereof, are specifically incorporated by reference in the accompanying application. Claims are open-ended, as opposed to closed, unless expressly stated otherwise. In various examples of the above, the term 'including' g' (include, include) means 'including, without limitati on' (including but not limited to...), or 'including but not limited to...' t limited to' (including, but not limited to) The term 'comprising' shall be read as follows: When used in writing, 'including' and 'contain' 'containing' or 'characterized by' is synonymous with (and is inclusive or open-ended) and may include further elements or does not exclude any unrecited element or method step; the term 'having '(having)' means 'having at least' the term 'includes' shall be interpreted as 'including' es but is not limited to'(... The term 'example' should be interpreted as meaning the It is used to provide illustrative examples of the items covered, not an exhaustive or exclusive enumeration thereof. It is not used to provide information; adjectives, such as 'known', 'normal', 'standard', and similar Terms of similar meaning may refer to the availability of the described item for a given period or at a given time. The statements in this document should not be construed as limiting the scope of the present or future publicly known or available at the time of must be read to encompass the art, ordinary art or standard art; 'preferably', 'preferred', 'd 'esired' (desired, wanted) or 'desirable' (preferred) The use of such terms and words of similar import indicates that certain features are essential to the structure or function of the invention. implying that something is crucial, essential, or even important to the function or These should not be construed as illustrative and not restrictive, but rather as being utilized in certain embodiments of the present invention. Highlight alternative or additional features that may or may not be utilized. In the same way, the conjunction 'and' A group of items connected by (and) means that each and every item in the group is should not be read as requiring the presence of Unless expressly stated otherwise, Similarly, statements connected by the conjunction 'or' must be The items in a group should not be read as requiring mutual exclusivity within the group. rather, unless expressly stated otherwise, they are used as 'and / or'. It must be read as follows.

[0186] Where a range of values is given, the upper and lower limits of the range and any values between the upper and lower limits are It is understood that each value in between is encompassed by an embodiment.

[0187] Substantially any plural and / or singular terminology used herein With respect to the use of the plural, those skilled in the art will recognize the plural as appropriate to the context and / or application. The various singular forms can be translated from singular to plural and / or singular to plural. / Plural interchanges may be explicitly indicated herein for clarity. The word ('a' or 'an') does not exclude a plurality. Other units may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not preclude the inclusion of these measures. There is no indication that a combination of stages cannot be advantageously used. shall not be construed as limiting the scope.

[0188] The specific number of claim recitations introduced is intended If so, such intention will be expressly set forth in the claims, and such In the absence of such a restrictive description, it is obvious to a person skilled in the art that no such intention exists. It will be further understood that, for example, as an aid to understanding, the following appended claims are To introduce claim limitations, use 'at least one' and and may include the use of the introductory phrase 'one or more'. However, the use of such phrases does not necessarily imply that the same claim is 'one or more'. or more) or 'at least one' introductory phrase and Even when it contains a definite article (e.g., 'a' or 'an'), the implied 'a' or 'an' The introduction of a claim limitation with a definite article shall not affect any invention that includes such introduced claim limitation. Any such particular claim may be limited to an embodiment containing only one such limitation. (e.g., 'a' and / or 'an' are typical Typically, 'at least one' or 'one or more' shall be construed to mean one or more; the same applies to The same applies to the use of definite articles used to introduce claim limitations. Even if a specific number of introduced claim limitations is explicitly stated, a person skilled in the art would be able to Such limitations should typically be construed to mean at least the number recited. (For example, the naked limitation of "two limitations" , i.e., typically at least two qualifying statements, unless accompanied by other modifiers: or three or more qualifying statements). In those cases where a convention similar to "one more" is used, such an interpretation is generally accepted by those skilled in the art. is intended in the sense that a person would understand the practice (e.g., "at least A, B, and C"). "A system having one or more" refers to a system having A alone, a system having B alone, A system with C alone, a system with A and B together, a system with A and C together A system having A and B together, and / or A, B, and C together. (This would include, but would not be limited to, systems that have In those cases where a convention similar to "at least one of A, B or C" is used, Such interpretation is intended in the sense that one of ordinary skill in the art would understand that practice (e.g., "A system having at least one of A, B, or C" includes a system having A alone, A system with B alone, a system with C alone, a system with A and B together a system having A and C together, a system having B and C together, and and / or a system having A, B, and C together, etc. Disjunctive words and / or phrases that give two or more alternative terms are Virtually no one, whether in the specification, claims or drawings, uses one of the terms (or It should be understood that various possibilities including either the term "or" or both terms are intended. It will be further understood by those skilled in the art that the phrase "A or B" must be " will be understood to include the possibilities of "A" or "B" or "A and B." cormorant.

[0189] All numbers expressing quantities of ingredients, reaction conditions, etc. used herein are in accordance with the term It is to be understood that "about" is modified in all instances. Therefore, unless indicated to the contrary, the numerical parameters set forth herein are within the realms of feasibility. These are approximations that may vary depending on the desired properties sought. In any application claiming priority to this application, in any attempt to limit the scope of any claim in Rather, each numerical parameter must be interpreted according to the number of significant figures and normal rounding techniques. must be interpreted.

[0190] Furthermore, the above has been described in some detail as an illustration and example for purposes of clarity and understanding. Notwithstanding the foregoing, it will be apparent to those skilled in the art that certain changes and modifications may be made. It is therefore understood that the description and examples should be construed as limiting the scope of the invention as set forth herein. The present invention should not be construed as being limited to the specific embodiments and examples set forth herein, but rather as being shall also be construed to embrace all modifications and alternatives that come within the true scope and spirit of the It must be.

Claims

[Claim 1] The invention described in the specification.

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