WO2018163716A1 - Agent anti-inflammatoire, composition médicinale contre l'inflammation, et composition alimentaire contre l'inflammation - Google Patents

Agent anti-inflammatoire, composition médicinale contre l'inflammation, et composition alimentaire contre l'inflammation Download PDF

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Publication number
WO2018163716A1
WO2018163716A1 PCT/JP2018/004727 JP2018004727W WO2018163716A1 WO 2018163716 A1 WO2018163716 A1 WO 2018163716A1 JP 2018004727 W JP2018004727 W JP 2018004727W WO 2018163716 A1 WO2018163716 A1 WO 2018163716A1
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inflammation
protein catabolism
inflammatory agent
present
inflammatory
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PCT/JP2018/004727
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English (en)
Japanese (ja)
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恵樹 郡山
宏冶 鈴木
恵一 平本
森田　明広
野坂　直久
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日清オイリオグループ株式会社
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Priority to JP2018543736A priority Critical patent/JP6470879B1/ja
Priority to CN201880011488.4A priority patent/CN110290785A/zh
Publication of WO2018163716A1 publication Critical patent/WO2018163716A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to an anti-inflammatory agent, an anti-inflammatory pharmaceutical composition, and an anti-inflammatory food composition.
  • Protein is a major component of muscles and organs in the body. In vivo, the cycle of assimilation (synthesis) and catabolism (decomposition) of proteins is repeated, and in normal times, the balance between assimilation and catabolism is maintained.
  • protein catabolism occurs, and the above assimilation and catabolism occur.
  • the balance with is inclined to catabolism.
  • the surplus protein source generated by the increased protein catabolism is converted into carbohydrates in the liver, and the carbohydrates excessively converted due to malnutrition or metabolic abnormalities can cause cell damage and organ damage.
  • Such cell damage and organ damage promote the production of inflammatory cytokines of immune system cells via hyperglycemia due to a decrease in carbohydrate metabolism.
  • a situation in which the nutritional state is poor or an increase in protein catabolism at the time of invasion further causes inflammation in the body and further lowers the biological defense function.
  • Patent Documents 1 and 2 Various anti-inflammatory agents for suppressing inflammation induced in the body are known (see, for example, Patent Documents 1 and 2).
  • anti-inflammatory agents may have problems such as side effects and may not be suitable for continuous administration.
  • anti-inflammatory agents that can suppress inflammation during increased protein catabolism for example, inflammation during increased protein catabolism due to undernutrition, inflammation during increased protein catabolism due to invasion have not been sufficiently studied.
  • An object of the present invention is to provide an anti-inflammatory agent with less side effects even when continuously administered.
  • the present inventors have found that medium-chain fatty acids have an unexpected anti-inflammatory action, and can effectively suppress inflammation particularly during protein catabolism, and have completed the present invention. Specifically, the present invention provides the following.
  • Anti-inflammatory agent containing medium chain fatty acid as an active ingredient.
  • the anti-inflammatory agent according to (1) which contains a medium chain fatty acid triglyceride as the medium chain fatty acid.
  • inflammation at the time of increased protein catabolism is inflammation at the time of increased protein catabolism by undernutrition and / or inflammation at the time of increased protein catabolism by invasion.
  • the anti-inflammatory agent according to any one of (1) to (4) for preventing or treating inflammation in the brain.
  • An anti-inflammatory pharmaceutical composition comprising the anti-inflammatory agent according to any one of (1) to (5).
  • An anti-inflammatory food composition comprising the anti-inflammatory agent according to any one of (1) to (5).
  • inflammation at the time of increased protein catabolism is inflammation at the time of increased protein catabolism due to undernutrition and / or inflammation at the time of increased protein catabolism due to invasion.
  • an anti-inflammatory agent with less side effects even when continuously administered.
  • the anti-inflammatory agent of the present invention contains a medium chain fatty acid as an active ingredient.
  • medium chain fatty acid is also referred to as “MCFA”.
  • Constant chain fatty acid as an active ingredient means that at least medium chain fatty acid is contained as a physiologically active substance contained in the anti-inflammatory agent of the present invention.
  • Increased protein catabolism promotes the production of inflammatory cytokines by cells and organs as well as immune system cells.
  • inflammatory cytokines by cells and organs as well as immune system cells.
  • neuropathy depression, schizophrenia, etc.
  • diseases associated with neurodegeneration Parkinson disease, etc.
  • suppressing inflammation in the brain leads to maintaining cognitive functions such as judgment and the like, thus preventing a need for nursing care and lowering of daily living activities.
  • the present inventors have not only normal inflammation (for example, inflammation that does not involve nutritional status or invasion), but also inflammation at the time of increased protein catabolism, and further, inflammation and / or invasion at the time of increased protein catabolism due to undernutrition.
  • anti-inflammatory agents containing medium-chain fatty acids as active ingredients can effectively suppress inflammation, particularly inflammation during protein catabolism, and further, inflammation during protein catabolism due to undernutrition. It was also found that the protein catabolism increase due to invasion can be effectively suppressed.
  • Medium chain fatty acids are components that are widely blended in foods and the like, and have high safety. Therefore, the anti-inflammatory agent of the present invention has low side effects even if it is continuously administered.
  • “continuous administration” means that the anti-inflammatory agent of the present invention is continuously or intermittently administered to a subject over a predetermined period.
  • an embodiment in which the anti-inflammatory agent of the present invention is administered once to a subject is not excluded.
  • MCFA Medium chain fatty acid
  • MCFA is a straight-chain saturated fatty acid having 6 to 12 carbon atoms, and is an oil / fat component contained in ordinary foods (for example, edible oils and fats and dairy products).
  • MCFA is preferably a straight-chain saturated fatty acid having 8 to 12 carbon atoms, and a straight-chain saturated fatty acid having 8 and / or 10 carbon atoms from the viewpoint that a safer anti-inflammatory agent can be easily obtained. Is more preferable.
  • Specific MCFAs include caproic acid (n-hexanoic acid), caprylic acid (n-octanoic acid), capric acid (n-decanoic acid), and lauric acid.
  • MCFA can be obtained, for example, by hydrolyzing palm kernel oil or palm oil and then refining it. Moreover, a commercial item and a reagent can also be used as MCFA.
  • the form of MCFA contained in the anti-inflammatory agent is not particularly limited, and may be a medium chain fatty acid itself, and a fatty acid precursor (for example, a salt, ester (acyl described later) that is converted into a medium chain fatty acid in vivo. Glycerol))) or a mixture thereof.
  • a fatty acid precursor for example, a salt, ester (acyl described later) that is converted into a medium chain fatty acid in vivo. Glycerol)
  • MCFA is usually taken into the body in the form of a fatty acid precursor, more specifically, acylglycerol in which MCFA and glycerin are ester-bonded. It is known that ingested acylglycerol is decomposed and absorbed in the digestive tract and releases MCFA, and is energized in the liver. From the viewpoint of higher safety and the like, the form of MCFA contained in the anti-inflammatory agent of the present invention is preferably acylglycerol.
  • Acylglycerol has a structure in which fatty acid and glycerin are ester-bonded, and exists in one of three forms (monoacylglycerol, diacylglycerol, and triacylglycerol) depending on the number of fatty acids that bind to glycerin. To do.
  • the acylglycerol in the present invention may be in any of the above three forms, but at least one of the constituent fatty acids is MCFA.
  • the acylglycerol in the present invention is preferably triacylglycerol from the viewpoint of being close to a normal food form.
  • the fatty acids constituting diacylglycerol and triacylglycerol may be the same or different.
  • acylglycerol composed of different types of fatty acids
  • the binding position of each fatty acid to glycerin is not particularly limited.
  • fatty acids other than MCFA for example, long-chain fatty acids having 14 to 22 carbon atoms
  • the lower limit of the proportion of MCFA is preferably 10% by mass or more, more preferably 40% by mass or more, and more preferably 80% by mass or more.
  • the upper limit is preferably 100% by mass or less. If it is the said range, the anti-inflammatory action by MCFA can be exhibited more effectively.
  • the acyl glycerol which contains MCFA as a constituent fatty acid is mix
  • the method for producing acylglycerol is not particularly limited.
  • it can be obtained by esterifying palm kernel oil or MCFA derived from palm oil and glycerin.
  • esterification reaction include a method of reacting in a non-catalytic and solvent-free manner under pressure, a method of reacting using a synthetic catalyst such as sodium methoxide, a method of reacting using lipase as a catalyst, and the like. .
  • the acylglycerol in the present invention contains MCFA and a long chain fatty acid (for example, a linear long chain fatty acid having 14 to 22 carbon atoms) as a constituent fatty acid.
  • Triglycerides to be used that is, medium and long chain fatty acid triglycerides are preferred.
  • the acylglycerol in the present invention is particularly preferably a triglyceride in which all of the constituent fatty acids are MCFA, that is, a medium-chain fatty acid triglyceride.
  • MLCT intermediate chain fatty acid triglyceride
  • MCT medium chain fatty acid triglyceride
  • the form of MCFA contained in the anti-inflammatory agent of the present invention preferably contains MLCT and / or MCT, and more preferably contains only MCT.
  • the anti-inflammatory agent of the present invention is particularly preferably composed of MCT.
  • the anti-inflammatory agent of the present invention may be composed of MCFA (MCFA itself, MCFA fatty acid precursor (MLCT, MCT, etc.), or a mixture thereof), but contains components other than MCFA together with MCFA. May be.
  • the lower limit of the amount of MCFA (MCFA itself, MCFA fatty acid precursor (MLCT, MCT, etc.), or a mixture thereof) included in the anti-inflammatory agent
  • the value is preferably 33% by mass or more, more preferably 50% by mass or more with respect to the anti-inflammatory agent.
  • the upper limit is preferably 99% by mass or less, more preferably 90% by mass or less. If it is the said range, the anti-inflammatory action by MCFA can be exhibited more effectively.
  • Components other than MCFA contained in the anti-inflammatory agent of the present invention are not particularly limited as long as they do not inhibit the action of MCFA.
  • examples of such components include active ingredients (tranexamic acid, acetylsalicylic acid, etc.) known to have an anti-inflammatory action, antioxidants, and emulsifiers.
  • active ingredients tranexamic acid, acetylsalicylic acid, etc.
  • antioxidants antioxidants
  • emulsifiers emulsifiers.
  • the types and blending amounts of these components can be appropriately set according to the effect to be obtained.
  • the content of MCFA contained in the anti-inflammatory agent of the present invention can be specified by gas chromatography.
  • the anti-inflammatory agent of the present invention can be used for prevention or treatment of inflammation, particularly inflammation during protein catabolism (for example, protein catabolism that occurs during malnutrition or eating disorders, or protein catabolism due to invasion).
  • prevention means, for example, suppression or delay of the onset of inflammation
  • treatment refers to, for example, delaying the progression of inflammation, and alleviating, reducing, improving, and curing symptoms. means.
  • inflammation refers to various reaction mechanisms caused by various stimuli, damage, infection, and the like. Whether inflammation is induced can be identified using a known inflammation marker. Examples of the inflammatory marker include IL-1 ⁇ , iNOS, TNF- ⁇ , INF- ⁇ , cox-2, and NF- ⁇ B.
  • the anti-inflammatory agent of the present invention is particularly effective against inflammation during protein catabolism due to undernutrition and / or inflammation during protein catabolism due to invasion.
  • enhanced protein catabolism refers to a state in which the balance between assimilation and catabolism of proteins in a living body is inclined to catabolism.
  • “enhanced protein catabolism due to undernutrition” means that the amount of energy intake is insufficient as in undernutrition or eating disorders, and protein degradation is enhanced to produce carbohydrates in the body. Refers to the state.
  • intensification of protein catabolism by invasion means that metabolic changes such as repair of damaged tissues occur due to surgery, trauma, burns, infection with pathogenic microorganisms, malignant tumors, etc., and protein degradation is accelerated. Refers to the state.
  • inflammation at the time of increased protein catabolism and “inflammation at the time of increased protein catabolism by undernutrition and / or inflammation at the time of increased protein catabolism by invasion” are proteins caused by the various factors described above. When catabolism is increased, it refers to various reaction mechanisms caused by various stimuli, injuries, infections, etc., and produces signs such as redness, heat, swelling, and pain.
  • the inflammation at the time of increased protein catabolism due to undernutrition and the inflammation at the time of increased protein catabolism due to invasion refers to the inflammation at the time of increased protein catabolism due to undernutrition and the inflammation at the time of increased protein catabolism due to invasion. Refers to the state in which both occur.
  • Whether or not increased protein catabolism occurs in vivo can be identified using a blood marker.
  • blood markers include C-reactive protein (CRP), albumin (ALB), ⁇ 1-antitrypsin ( ⁇ 1-AT), haptoglobin (Hp), serum amyloid A (SAA), sialic acid (SA), Examples include transthyretin (TTR).
  • reference value refers to the range of normal values of each marker.
  • CRP increases during protein catabolism.
  • a typical reference value for CRP is about 0.2 to 0.5 mg / dL.
  • the CRP value increases to mild (0.5 to 2.0 mg / dL), moderate (2.0 to 10 mg / dL), and high (10 to mg / dL), the inflammatory state associated with infections, etc. Becomes prominent.
  • ALB decreases.
  • the decrease in ALB is due to the suppression of protein synthesis in the liver, inflammation caused by invasion or disease is suspected as one of the causes.
  • ⁇ 1-AT increases when protein catabolism increases.
  • the reference value of ⁇ 1-AT varies depending on gender and age. For example, in the case of 40 to 59 years old, it is 116 to 154 mg / dL for men and 123 to 161 mg / dL for women. When the value of ⁇ 1-AT is 200 mg / dL or more, it is suspected that protein catabolism has occurred.
  • Hp increases when protein catabolism increases. Although the reference value of Hp varies depending on the genotype (phenotype), it is 41 to 273 mg / dL for type 2-2, which is said to have the highest frequency of phenotype in Japan. When the value of Hp is 320 mg / dL or more, it is suspected that protein catabolism has occurred.
  • SAA increases during protein catabolism. As the SAA value increases to mild (10-50 ⁇ g / mL), moderate (50-300 ⁇ g / mL), and high (300 or more ⁇ g / mL), the inflammatory state becomes more prominent.
  • SA increases when protein catabolism increases.
  • the reference value for SA is 44 to 71 mg / dL. If SA increases, it is suspected that inflammation has occurred.
  • TTR decreases when protein catabolism increases. If the TTR value is 22 mg / dL or less, inflammation is suspected.
  • a living body is undernutrition
  • protein catabolism is enhanced due to undernutrition.
  • Whether a living body is undernourished can be specified using a blood marker.
  • blood markers include albumin (ALB), ⁇ 1-antitrypsin ( ⁇ 1-AT), cholinesterase (ChE), transferrin (Tf), transthyretin (TTR), urea nitrogen (BUN), cholesterol (Cho ) And the like.
  • reference value refers to the range of normal values of each marker.
  • a typical standard value for ALB is about 3.7 to 4.9 g / dL. As the ALB value decreases to mild (3.2 to 3.7 g / dL), moderate (2.5 to 3.2 g / dL), and high (to 2.5 g / dL), the nutritional status is poor. Suspected to be.
  • ⁇ 1-AT decreases during undernutrition.
  • the reference value for ⁇ 1-AT is 94 to 150 mg / dL. If the value of ⁇ 1-AT is 25 mg / dL or less, it is suspected that the nutritional state is poor.
  • ChE decreases during undernutrition.
  • the reference value for ChE is 242 to 495 U / L for men and 200 to 459 U / L for women.
  • Tf decreases at low nutrition.
  • the reference value for Tf is 190-300 mg / dL for men and 200-340 mg / dL for women.
  • TTR decreases during undernutrition.
  • the reference value for TTR is 22.0-40.0 mg / dL.
  • BUN is reduced during undernutrition.
  • the reference value for BUN is 8 to 20 mg / dL for men, but a low value of about 10 to 20% is the reference value for women.
  • the value of BUN is 8 mg / dL or less, it is suspected that the nutritional state is poor.
  • C Cho decreases during undernutrition.
  • the reference value for Cho is 150-220 mg / dL. If the value of Cho is 150 mg / dL or less, it is suspected that the nutritional state is poor.
  • the site to which the anti-inflammatory agent of the present invention can be applied is not limited, and can be applied to any site in the body (brain, cardiovascular, liver, kidney, etc.).
  • the anti-inflammatory agent of the present invention is particularly applicable to inflammation in the brain (hippocampus etc.). It is known that inflammation in the brain is accompanied by the production of neuropathy factors (inflammatory cytokines, active oxygen, nitric oxide, etc.) by the activation of microglia in the brain. Specific symptoms of inflammation in the brain include abnormal mitochondrial function in neurons, increased oxidative stress, and abnormal protein deposition. These symptoms affect the development of neurodegenerative diseases (such as Parkinson's disease). . Therefore, the anti-inflammatory agent of the present invention can be effective against neurodegenerative diseases.
  • neuropathy factors inflammatory cytokines, active oxygen, nitric oxide, etc.
  • an inflammation marker for example, It can be suppressed by suppressing the expression (especially expression in the brain) of one or more selected from the group consisting of IL-1 ⁇ , TNF- ⁇ , and iNOS.
  • the anti-inflammatory agent of the present invention can be applied for producing an anti-inflammatory pharmaceutical composition.
  • An anti-inflammatory pharmaceutical composition containing the anti-inflammatory agent of the present invention (hereinafter also referred to as “the pharmaceutical composition of the present invention”) is less likely to cause side effects and can be preferably used as a pharmaceutical suitable for continuous administration.
  • the form of the pharmaceutical composition of the present invention is not particularly limited, but it can be prepared as either a pharmaceutical composition for oral administration or a pharmaceutical composition for parenteral administration. From the viewpoint of easy continuous consumption, the pharmaceutical composition of the present invention is preferably a pharmaceutical composition for oral administration.
  • Examples of the form of the pharmaceutical composition for oral administration include preparations such as capsules, tablets, pills, powders, fine granules, granules, liquids, and syrups.
  • Examples of the form of a pharmaceutical composition for parenteral administration include preparations such as injections and infusions.
  • the pharmaceutical composition of the present invention is preferably a composition comprising the anti-inflammatory agent of the present invention and pharmacologically and pharmaceutically acceptable additives.
  • pharmacologically and pharmaceutically acceptable additive a substance that is usually used as an excipient or the like in the pharmaceutical field and does not react with an active ingredient contained in the anti-inflammatory agent of the present invention can be used.
  • the dosage of the pharmaceutical composition of the present invention can be appropriately set according to the administration purpose (prevention or treatment), administration method, administration period, and other various conditions (eg, patient's symptoms, age, body weight).
  • the dosage of the pharmaceutical composition of the present invention is preferably 0.02 g / kg body weight / day or more, more preferably 0.08 g / kg body weight / day, when the lower limit is converted into the amount of MCFA.
  • the upper limit is preferably set to 0.70 g / kg body weight / day or less, more preferably 0.45 g / kg body weight / day or less in terms of the amount of MCFA.
  • the dosage of the pharmaceutical composition of the present invention is preferably 0.03 g / kg body weight / day or more, more preferably 0.09 g / kg body weight / day when the lower limit is converted into the amount of MCT.
  • About an upper limit it can convert into the quantity of MCT, Preferably it can set to below 1.00 g / kg body weight / day, More preferably, it is below 0.50 g / kg body weight / day.
  • the dosage of the pharmaceutical composition of the present invention is preferably 0.026 g / kg body weight / day or more, more preferably 0.09 g / kg body weight when the lower limit is converted to the amount of MCFA.
  • / Can be set to more than a day.
  • the upper limit is preferably set to 0.72 g / kg body weight / day or less, more preferably 0.56 g / kg body weight / day or less in terms of the amount of MCFA.
  • the dosage of the pharmaceutical composition of the present invention is preferably 0.029 g / kg body weight / day or more, more preferably 0.10 g / kg body weight when the lower limit is converted to the amount of MCT.
  • / Can be set to more than a day.
  • About an upper limit it can convert into the quantity of MCT, Preferably it is 0.80 g / kg body weight / day or less, More preferably, it can set to 0.60 g / kg body weight / day or less.
  • the above dose is preferably administered over several hours (eg, over 4 to 8 hours).
  • the pharmaceutical composition of the present invention is less likely to cause side effects and is less likely to cause interaction with general active ingredients, existing drugs (anti-inflammatory agents, anti-cancer agents, lifestyle-related diseases (high blood pressure, It may be used in combination with diabetes, dyslipidemia, etc.) and other therapeutic agents.
  • existing drugs anti-inflammatory agents, anti-cancer agents, lifestyle-related diseases (high blood pressure, It may be used in combination with diabetes, dyslipidemia, etc.
  • the existing drug combined with the pharmaceutical composition of the present invention is an anti-inflammatory agent, the dose of the existing drug can be lowered, so that side effects of the existing drug can be reduced.
  • the pharmaceutical composition of the present invention is suitable for continuous administration because there are few side effects.
  • the administration period is not particularly limited, and can be set to 3 to 10 days, for example. Administration may be performed every several hours during the above period or at intervals (eg, 1 to several days).
  • the anti-inflammatory agent of the present invention can be applied for the production of an anti-inflammatory food composition.
  • MCFA which is an active ingredient of the anti-inflammatory agent of the present invention, is not only less susceptible to side effects, but is less likely to impair the flavor and palatability of food. Therefore, the anti-inflammatory food composition containing the anti-inflammatory agent of the present invention (hereinafter also referred to as “the food composition of the present invention”) can be preferably used as a food that is easy to eat.
  • the form of the food composition of the present invention includes supplements, general foods, animal foods, and animal feeds.
  • the form of the supplement is not particularly limited, and may be either a solid preparation or a liquid preparation.
  • preparations such as tablets, coated tablets, capsules, granules, powders, powders, sustained-release preparations, suspensions, emulsions, internal liquids, dragees, pills, fine granules, syrups, elixirs, etc. Can be mentioned.
  • the form of the general food is not particularly limited.
  • bread / confectionery bread, cake, cookies, biscuits, donuts, muffins, scones, chocolate, snacks, whipped cream, ice cream, etc.
  • beverages fruit juices, nutrition Drinks, sports drinks, etc.
  • soups seasoned foods (dressing, sauce, mayonnaise, butter, margarine, prepared margarine, etc.), fat spread, shortening, bakery mix, fried oil, frying oil, fried food, processed meat products.
  • Examples include frozen foods, fried foods, noodles, retort foods, liquid foods, and swallow foods.
  • the anti-inflammatory agent of the present invention When used for the production of general foods, it is added to the raw material in the form of MLCT and / or MCT (more preferably MCT), or the fat or oil of the raw material is added to MLCT and / or MCT (more Preferably, it is used by replacing with MCT).
  • the intake amount of the food composition of the present invention can be appropriately set according to the purpose of intake (prevention or treatment), the intake period, and other various conditions (for example, the symptom, age, and body weight of the eating person).
  • the intake of the food composition of the present invention can be set to a lower limit value of preferably 0.02 g / kg body weight / day or more, more preferably 0.08 g / kg body weight / day or more in terms of MCFA.
  • the upper limit is preferably set to 0.70 g / kg body weight / day or less, more preferably 0.45 g / kg body weight / day or less in terms of the amount of MCFA.
  • the intake of the food composition of the present invention can be set at a lower limit value of preferably 0.03 g / kg body weight / day or more, more preferably 0.09 g / kg body weight / day or more in terms of the amount of MCT. .
  • a lower limit value preferably 0.03 g / kg body weight / day or more, more preferably 0.09 g / kg body weight / day or more in terms of the amount of MCT.
  • a lower limit value of preferably 0.03 g / kg body weight / day or more, more preferably 0.09 g / kg body weight / day or more in terms of the amount of MCT.
  • a lower limit value preferably 0.03 g / kg body weight / day or more, more preferably 0.09 g / kg body weight / day or more in terms of the amount of MCT.
  • About an upper limit it can convert into the quantity of MCT, Preferably it can set to below 1.00 g / kg body weight / day, More
  • test meals and model mice were prepared, and the expression level of inflammatory markers was evaluated.
  • the MCT manufactured by Nisshin Oillio Group, Inc.
  • mice were prepared that had inflammation during protein catabolism (inflammation during protein catabolism due to undernutrition and inflammation during protein catabolism due to invasion).
  • undernutrition (PEM) model mice with poor nutritional status were prepared.
  • lipopolysaccharide hereinafter, also referred to as “LPS” was intraperitoneally administered to the mice as an invasive treatment, and target mice were obtained.
  • LPS lipopolysaccharide
  • target mice were obtained.
  • LPS is a toxin derived from the outer membrane of the Gram-negative bacterial cell wall that causes inflammation. It is known that administration of LPS induces a state of increased protein catabolism in mice and causes inflammation not only in various organs throughout the body but also in the brain hippocampus.
  • PEM model mice were prepared according to a known method (reference: Journal of Nutritional Science and Vitaminology Vol. 54 (2008) No. 5 P 371-377). Specifically, 12 14-week-old C57BL / 6 adult male mice (6 mice x 2 groups (comparative examples and examples)) were bred for 1 week. Then, according to each group, the test diet (“PEM-LCT” or “PEM-MCT”) shown in Table 1 was given and reared for 2 weeks (the test diet and water were freely consumed), and the PEM model mice were Obtained.
  • PEM-LCT test diet
  • mice (6 mice) fed with a normal diet were prepared as a control group.
  • LPS from Escherichia coli 0111: B4, Sigma-Aldrich
  • the brain hippocampus was collected from the mice on the 17th day (3 days after LPS administration) after the start of feeding the test meal. Each mouse was fasted 1 day before collecting the hippocampus, and fasted 3 hours before collecting the hippocampus.
  • ⁇ Quantification of inflammation marker mRNA> In the brain hippocampus collected from each test group, mRNA expression levels of three kinds of inflammation markers (IL-1 ⁇ , iNOS, and TNF- ⁇ ) were measured. By measuring the mRNA expression level of these inflammation markers, the degree of inflammation of the brain hippocampus can be specified.
  • RNA was isolated from the brain hippocampus collected from each test group using an RNA extraction kit (Sepasol RNA I, Nacalai Tesque). Subsequently, the expression level of mRNA was measured using the reagents and primers shown in Table 2 using a PCR apparatus (trade name “PC818”, manufactured by ASTEC).
  • the mRNA expression levels of inflammation markers (IL-1 ⁇ , iNOS, and TNF- ⁇ ) in each test group are shown in Table 3 and FIG.
  • the expression level of mRNA is expressed as the average value of the relative value ⁇ standard error (%) when the expression value in each test group is 100, and the average value of the expression level of mRNA in the normal diet (control) is 100. Identified.
  • the Tukey method was used for the test of significant difference between trials.
  • the mRNA expression level was significantly lower for any inflammation marker as compared to the “PEM-LCT” intake group. That is, it can be seen that the inflammation induced in the brain hippocampus by the malnutrition diet and the invasive treatment can be suppressed by ingestion of MCT.

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Abstract

La présente invention cherche à résoudre le problème qui est de fournir un agent anti-inflammatoire qui présente peu de risque d'effets indésirables même s'il est administré en continu. L'invention concerne : un agent anti-inflammatoire contenant comme principe actif un acide gras à chaîne moyenne ; et une composition médicinale contre l'inflammation ou une composition alimentaire contre l'inflammation, comprenant l'agent anti-inflammatoire susmentionné. L'invention peut comprendre, en tant qu'acide gras à chaîne moyenne, un acide gras à chaîne moyenne de type triglycéride. La présente invention est destinée à être utilisée de préférence pour prévenir ou traiter une inflammation associée à un catabolisme protéique anormalement élevé (par exemple, une inflammation associée à un catabolisme protéique anormalement élevé lié à une malnutrition ou une inflammation associée à un catabolisme protéique anormalement élevé lié à une invasion).
PCT/JP2018/004727 2017-03-08 2018-02-09 Agent anti-inflammatoire, composition médicinale contre l'inflammation, et composition alimentaire contre l'inflammation WO2018163716A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004043337A (ja) * 2002-07-10 2004-02-12 Nisshin Oillio Ltd 血中中性脂肪濃度調整剤
JP2005526768A (ja) * 2002-03-18 2005-09-08 ファーモス コーポレイション 炎症関連遺伝子を調節するデキサナビノール及びデキサナビノール類似体
WO2016033699A1 (fr) * 2014-09-05 2016-03-10 Rsem, Limited Partnership Compositions et méthodes pour traiter et prévenir l'inflammation

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ES2745849T3 (es) * 2008-12-05 2020-03-03 Ajinomoto Kk Composición nutricional

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
JP2005526768A (ja) * 2002-03-18 2005-09-08 ファーモス コーポレイション 炎症関連遺伝子を調節するデキサナビノール及びデキサナビノール類似体
JP2004043337A (ja) * 2002-07-10 2004-02-12 Nisshin Oillio Ltd 血中中性脂肪濃度調整剤
WO2016033699A1 (fr) * 2014-09-05 2016-03-10 Rsem, Limited Partnership Compositions et méthodes pour traiter et prévenir l'inflammation

Non-Patent Citations (1)

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Title
KONO, HIROSHI ET AL., JOURNAL OF JAPANESE SOCIETY FOR MEDICAL USE OF FUNCTIONAL FOODS, vol. 8, no. 4, October 2014 (2014-10-01), pages 264 - 270, ISSN: 1348-2564 *

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