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WO2023157948A1 - Composition orale - Google Patents

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Publication number
WO2023157948A1
WO2023157948A1 PCT/JP2023/005745 JP2023005745W WO2023157948A1 WO 2023157948 A1 WO2023157948 A1 WO 2023157948A1 JP 2023005745 W JP2023005745 W JP 2023005745W WO 2023157948 A1 WO2023157948 A1 WO 2023157948A1
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Prior art keywords
group
glycerol
composition
liver
phosphate
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English (en)
Japanese (ja)
Inventor
主弥 池口
邦彦 相馬
典孝 吉川
伸之 川崎
敢 武久
岳 江原
雅史 細川
史章 別府
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Hokkaido University NUC
DIC Corp
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Hokkaido University NUC
DIC Corp
Dainippon Ink and Chemicals Co Ltd
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Priority to JP2024501448A priority Critical patent/JPWO2023157948A1/ja
Publication of WO2023157948A1 publication Critical patent/WO2023157948A1/fr
Anticipated expiration legal-status Critical
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    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to compositions that are orally ingested or administered.
  • the present invention also relates to methods for increasing muscle or strength, inhibiting muscle or strength loss, improving glucose metabolism, inhibiting fat accumulation in the liver, and improving the balance of omega-3 and omega-6 fatty acids in the body.
  • Lipids are one of the three major nutrients, and while they occupy an important position as an energy source, it is known that certain lipids have excellent physiological activity.
  • EPA eicosapentaenoic acid
  • EPA is one of the omega-3 fatty acids, which is essential for fetal development, lowers blood neutral fat (triglyceride), reduces the risk of cardiovascular disease, contributes to the prevention of Alzheimer's disease, etc. has been reported (Non-Patent Document 1).
  • EPA is also reported to have the effect of suppressing the production of inflammatory lipid mediators such as prostaglandins and leukotrienes from the omega-6 fatty acid arachidonic acid. Furthermore, it is known that EPA itself becomes an anti-inflammatory lipid mediator through metabolism and suppresses inflammation.
  • Patent Document 1 describes a cerebral atrophy inhibitor containing, as an active ingredient, a phospholipid containing a highly unsaturated fatty acid as a constituent fatty acid.
  • the subject of the present invention relates to the provision of novel functional lipid components that can be orally ingested or administered.
  • compositions having a molar ratio of ethanolamine phosphate moieties to 0.01 to 100 can provide unique physiological activities when orally ingested or administered to a subject, thus completing the present invention.
  • the present invention includes the following aspects.
  • glycerol-1-phosphate moiety CH 2 OH-CHOH-CH 2 -OPO 2 - -
  • ethanolamine phosphate moiety NH 3 + -CH 2 -CH 2 -OPO 2 - -
  • eicosapentaenoic acid moiety CH 3 CH 2 (CH ⁇ CHCH 2 ) 5 (CH 2 ) 2 CO—
  • the molar ratio of ethanolamine phosphate moieties to glycerol-1-phosphate moieties is from 0.01 to 100; Compositions taken or administered orally.
  • [2] The composition of [1], wherein the molar ratio of said eicosapentaenoic acid moieties to the sum of said glycerol-1-phosphate moieties and ethanolamine phosphate moieties is from 0.01 to 20.
  • Phospholipid represented by formula (I) (wherein R 1 and R 2 are selected from hydrogen atoms and acyl groups, at least one of R 1 and R 2 is an eicosapentaenoic acid moiety; X is selected from glycerol-1-phosphate moieties and ethanolamine phosphate moieties).
  • [5] containing an extract of Shewanella woodyi or a variant thereof, The composition according to [4].
  • [6] The composition according to [5], which contains an extract of Shewanella woodyi strain GS001 (accession number NITE BP-03460) or a mutant strain thereof.
  • [7] For at least one selected from the group consisting of increasing muscle or muscle strength, suppressing muscle or muscle strength loss, improving glucose metabolism, suppressing fat accumulation in the liver, and improving the balance of omega-3 fatty acids and omega-6 fatty acids in the body.
  • [11] For at least one selected from the group consisting of increasing muscle or muscle strength, suppressing muscle or muscle strength loss, improving glucose metabolism, suppressing fat accumulation in the liver, and improving the balance of omega-3 fatty acids and omega-6 fatty acids in the body.
  • [12] For the manufacture of orally ingested or administered formulations used for the prevention or improvement of at least one selected from the group consisting of diabetes, fatty liver, inflammation, locomotive syndrome, sarcopenia, lifestyle-related diseases and metabolic syndrome Use of the composition according to any one of [1] to [6].
  • composition according to any one of [1] to [6], which is used for maintaining or promoting expression of ELOVL2, ELOVL5, FADS1 or FADS2 gene in vivo [14] A method for maintaining or promoting ELOVL2, ELOVL5, FADS1 or FADS2 gene expression in the body, comprising an effective amount of the composition according to any one of [1] to [6]. A method comprising administering to or ingesting by a subject.
  • composition of the present invention can be ingested or administered orally. And, the composition of the present invention can be used for prevention or amelioration of diseases, symptoms or health conditions of subjects due to its unique physiological activity.
  • FIG. 1 is a graph showing fatty acid composition in SW oil.
  • 1 is a graph representing the fatty acid composition of ethanolamine-type phospholipids (PE) and glycerol-1-phosphate-type phospholipids (PG) fractions of SW oil.
  • PE ethanolamine-type phospholipids
  • PG glycerol-1-phosphate-type phospholipids
  • 1 is a flowchart of statistical analysis of Test Examples 1 to 3.
  • FIG. 4 is a graph showing changes in average food intake of mice in each group in Test Example 1.
  • FIG. 2 is a graph showing the gastrocnemius muscle weight of mice in each group after 6-week feeding in Test Example 1.
  • FIG. 2 is a graph showing fasting blood glucose levels of mice in each group on day 41 of feeding in Test Example 1.
  • FIG. 2 is a graph showing blood glucose levels of mice of each group on day 42 of breeding in Test Example 1, 2 hours after feeding.
  • FIG. 4 is a graph showing HbA1c values of mice in each group on day 42 of breeding in Test Example 1.
  • FIG. 4 is a graph showing liver weights of mice in each group after feeding for 6 weeks in Test Example 1.
  • FIG. 4 is a graph showing blood triglyceride levels of mice in each group after 6-week feeding in Test Example 1.
  • FIG. Graph showing blood total cholesterol level (T-CHO), LDL cholesterol level (LDL-CHO) and non-HDL cholesterol level (Non-HDL-CHO) in mice of each group after feeding for 6 weeks in Test Example 1.
  • T-CHO blood total cholesterol level
  • LDL-CHO LDL cholesterol level
  • Non-HDL-CHO non-HDL cholesterol level
  • FIG. 1 is a graph showing the fatty acid composition of n-3 polyunsaturated fatty acids (PUFA) in livers of mice of each group after feeding for 6 weeks in Test Example 1.
  • FIG. 4 is a graph showing the arachidonic acid (AA) content in the liver of mice of each group after four weeks of feeding in Test Example 2.
  • FIG. 4 is a graph showing the eicosapentaenoic acid (EPA) content in the liver of mice of each group after 4-week feeding in Test Example 2.
  • FIG. 4 is a graph showing the content of docosapentaenoic acid (DPA) in the liver of mice of each group after feeding for 4 weeks in Test Example 2.
  • DPA docosapentaenoic acid
  • FIG. 4 is a graph showing the content of docosahexaenoic acid (DHA) in the liver of mice of each group after 4-week feeding in Test Example 2.
  • FIG. 3 is a graph showing the expression level of ELOVL2 in the liver of mice of each group in Test Example 3.
  • FIG. 4 is a graph showing the expression level of ELOVL5 in the liver of mice of each group in Test Example 3.
  • FIG. 4 is a graph showing the expression level of FADS1 in the liver of mice of each group in Test Example 3.
  • FIG. 3 is a graph showing the expression level of FADS2 in the liver of mice of each group in Test Example 3.
  • saturated fatty acid refers to a fatty acid that does not contain a carbon-carbon double bond.
  • Unsaturated fatty acid also refers to a fatty acid containing at least one carbon-carbon double bond.
  • fatty acids are sometimes expressed in the form of "total number of carbon atoms: number of double bonds n-X", or in the form with C attached to the head.
  • nX means that the double bond first appears at the Xth carbon counted from the methyl end of the carbon chain of the fatty acid.
  • ⁇ -linolenic acid is represented as "18:3n-3" or "C18:3n-3".
  • nX represents a fatty acid in which only the total number of carbon atoms and the number of double bonds are specified.
  • acyl group corresponding to a specific fatty acid is a portion of the carboxyl group of the fatty acid excluding the OH portion, and is represented by the general formula R-CO- (R is an aliphatic hydrocarbon group). be.
  • phospholipid is a generic term for glycerophospholipids and sphingophospholipids.
  • Glycerophospholipids are glycerophospholipids in which one of the three hydroxyl groups of glycerin is phosphorylated. Of these, those in which both remaining hydroxyl groups are acylated are diacyl-type glycerophospholipids, and one of the remaining hydroxyl groups is acylated. Those only acylated are called lysophospholipids.
  • ethanolamine-type phospholipids (PE) and glycerol-1-phosphate-type phospholipids (PG) are ethanolamine phosphate and glycerol-1-phosphate, respectively, with a phosphate ester bond to the hydroxyl group at the 1-position. represents the phospholipids that In the present specification, phosphatidylethanolamine and phosphatidylglycerol represent diacyl glycerophospholipids containing ethanolamine phosphate and glycerol-1-phosphate as constituents, respectively.
  • ameliorating means ameliorating or alleviating the disease, condition or condition; preventing or slowing deterioration of the disease, condition or condition; or reversing the progression of the disease or condition. , stands for prevention or delay.
  • prevention of a disease, condition or condition means delaying or preventing the occurrence of the disease, condition or condition; reducing the risk of developing the disease, condition or condition; Represents a reduction in the rate of symptom incidence.
  • compositions Taken or Administered Orally
  • the composition of the invention is orally ingested or administered, glycerol-1-phosphate moiety (CH 2 OH-CHOH-CH 2 -OPO 2 - -), ethanolamine phosphate moiety (NH 3 + -CH 2 -CH 2 -OPO 2 - -) and eicosapentaenoic acid moiety ( containing CH 3 CH 2 (CH ⁇ CHCH 2 ) 5 (CH 2 ) 2 CO—),
  • the molar ratio of ethanolamine phosphate moieties to glycerol-1-phosphate moieties is 0.01-100.
  • compositions that can be orally ingested or administered may be referred to as an "oral composition”.
  • glycerol-1-phosphate moiety refers to a moiety of glycerol-1-phosphate excluding the hydrogen atom of the phosphate group, and has the structural formula CH 2 OH--CHOH--CH 2 --OPO 2 --. - is represented. A hydrogen ion or other cation may be associated with the phosphate group (OPO 2 ⁇ ) of the glycerol-1-phosphate moiety.
  • ethanolamine phosphate moiety refers to a portion of the phosphate group of ethanolamine phosphate from which hydrogen atoms are removed, represented by the structural formula NH 3 + —CH 2 —CH 2 —OPO 2 — . be done.
  • a hydrogen ion or other cation may be associated with the phosphate group of the ethanolamine phosphate moiety.
  • the state in which a hydrogen ion associates with the phosphate group of the glycerol-1-phosphate moiety or the ethanolamine phosphate moiety is CH 2 OH--CHOH--CH 2 --OPO 2 H-- or NH 3 + -CH 2 -CH 2 -OPO 2 H-, including a state in which hydrogen is bonded to a phosphoric acid moiety to form a hydroxyl group.
  • the other cations include alkali metal ions (sodium ion, potassium ion, etc.) and alkaline earth metal ions (magnesium ion, calcium ion, etc.).
  • the molar ratio of ethanolamine phosphate moieties to glycerol-1-phosphate moieties is From the viewpoint of exhibiting the effect remarkably, it is 0.01 or more, preferably 0.1 or more, more preferably 0.5 or more, still more preferably 1 or more, and even more preferably 1.5 or more.
  • the molar ratio of the ethanolamine phosphate moiety to the glycerol-1-phosphate moiety is 100 or less, preferably 50 or less, more preferably 20 or less, and still more preferably, from the viewpoint of significantly exhibiting the effects of the present invention. 10 or less, and even more preferably 5 or less.
  • Molar ratio of the eicosapentaenoic acid moiety to the sum of the glycerol-1-phosphate moiety and the ethanolamine phosphate moiety [(substance amount of eicosapentaenoic acid moiety)/(substance amount of glycerol-1-phosphate moiety + ethanolamine is not particularly limited, but is preferably 0.01 or more, more preferably 0.1 or more, still more preferably 0.2 or more, and further preferably More preferably, it is 0.4 or more.
  • the molar ratio of the eicosapentaenoic acid moiety to the total of the glycerol-1-phosphate moiety and the ethanolamine phosphate moiety is, for example, 20 or less, 10 or less, 5 or less, 4 or less, 3 or less, 2 or less, or 1 .5 or less.
  • the content of the eicosapentaenoic acid moiety in the oral composition of the present invention is, for example, 0.01% by mass or more, 0.1% by mass or more, 1% by mass or more, or 4% by mass, relative to the total amount of the oral composition. and may be 50% or less, 40% or less, or 30% or less by weight.
  • the content of C15:0 fatty acid relative to 100 parts by mass of eicosapentaenoic acid in the total lipid is preferably 5 parts by mass or more, more It is preferably 10 parts by mass or more, more preferably 15 parts by mass or more, and preferably 100 parts by mass or less, more preferably 70 parts by mass or less, and still more preferably 50 parts by mass or less.
  • the content of C16:1 fatty acid relative to 100 parts by mass of eicosapentaenoic acid in the total lipid is preferably 10 parts by mass or more, more It is preferably 15 parts by mass or more, preferably 300 parts by mass or less, more preferably 200 parts by mass or less.
  • the content of docosahexaenoic acid relative to 100 parts by mass of eicosapentaenoic acid in the total lipid is preferably 10 parts by mass or less, more preferably 5 parts by mass or less, and even more preferably 1 part by mass or less. be.
  • the glycerol-1-phosphate moiety, the ethanolamine phosphate moiety and the eicosapentaenoic acid moiety may constitute molecules different from each other.
  • said glycerol-1-phosphate moiety or said ethanolamine phosphate moiety may be present in the same molecule as said eicosapentaenoic acid moiety.
  • the oral composition of the present invention contains a molecule containing a glycerol-1-phosphate moiety and an eicosapentaenoic acid moiety, or a molecule containing an ethanolamine phosphate moiety and an eicosapentaenoic acid moiety, from the viewpoint of significantly exhibiting the effects of the present invention. It preferably contains at least and more preferably contains a molecule containing a glycerol-1-phosphate moiety and an eicosapentaenoic acid moiety and a molecule containing an ethanolamine phosphate moiety and an eicosapentaenoic acid moiety.
  • a phospholipid represented by the following formula (I) is preferable. Mentioned are: (wherein R 1 and R 2 are selected from hydrogen atoms and acyl groups, at least one of R 1 and R 2 is an eicosapentaenoic acid moiety; X is selected from glycerol-1-phosphate moieties and ethanolamine phosphate moieties).
  • the oral composition of the present invention preferably contains both a compound in which X is a glycerol-1-phosphate moiety and a compound in which X is an ethanolamine phosphate moiety in the formula (I).
  • X represents glycerol-1-phosphate moieties as EPA-bound glycerol-1-phosphate-type phospholipids (EPA-PG), and X represents ethanolamine phosphate moieties.
  • EPA-PG EPA-bound glycerol-1-phosphate-type phospholipids
  • EPA-PE EPA-bound ethanolamine-type phospholipids
  • the content of the EPA-bound ethanolamine-type phospholipid relative to 1 part by weight of the EPA-bound glycerol-1-phosphate-type phospholipid is 0.01 part by weight or more, preferably 0.01 part by weight. It is 1 part by mass or more, more preferably 0.5 parts by mass or more, still more preferably 1 part by mass or more, and even more preferably 1.5 parts by mass or more. Then, the content of the EPA-bound ethanolamine-type phospholipid with respect to 1 part by weight of the EPA-bound glycerol-1-phosphate-type phospholipid is 100 parts by weight or less, preferably, from the viewpoint of significantly exhibiting the effects of the present invention. It is 50 parts by mass or less, more preferably 20 parts by mass or less, still more preferably 10 parts by mass or less, and even more preferably 5 parts by mass or less.
  • the total carbon number of the acyl group of formula (I) is, for example, 3-35, preferably 9-31, more preferably 14-24.
  • the number of double bonds in the acyl group of formula (I) is, for example, 0-10, preferably 0-6, more preferably 0-5.
  • the acyl groups of R 1 and R 2 in the formula (I) are preferably acyl groups contained in phospholipids in organisms, more preferably C14:0 (myristic acid), C14:1, C15:0 ( pentadecanoic acid), C16:0 (palmitic acid), C16:1, C17:1, C18:0 (stearic acid), C18:1, C18:2, C18:3n-3 ( ⁇ -linolenic acid), C18: 3n-6 ( ⁇ -linolenic acid), C19:0, C20:0 (arachidic acid), C20: 1n-9 (cis-11-eicosenoic acid), C20:2n-6, C20:3n-3, C20: 3n-6 (dihomo- ⁇ -linolenic acid), C20: 4n-6 (arachidonic acid; AA), C20: 5n-3 (eicosapentaenoic acid; EPA), C22:0 (behenic acid), C22: 1
  • the total content of the phospholipids represented by the formula (I) is appropriately adjusted depending on the form, composition, purpose of use, usage, dosage, etc. of the oral composition.
  • the total content of phospholipids represented by formula (I) is, for example, 0.01% by mass or more, 0.1% by mass or more, 1% by mass or more, 10% by mass or more, relative to the total amount of the oral composition. , 20% by weight or more, or 50% by weight or more, and may be, for example, 100% by weight or less, 80% by weight or less, or 70% by weight or less.
  • the glycerol-1-phosphate moiety, the ethanolamine phosphate moiety and the eicosapentaenoic acid moiety of the oral composition of the present invention, and the phospholipid represented by the formula (I) may be derived from organisms. It may be synthesized, or it may be derived from a mixture of two or more of them, but from the viewpoint of safety in oral ingestion, preferably. Said organisms are, for example, selected from microorganisms (algae, bacteria, archaea, fungi, yeast, etc.), plants, marine and aquatic animals (eg, fish, crustaceans, etc.), and terrestrial animals.
  • the oral composition of the present invention preferably contains an extract of a bacterium of the genus Shewanella or a mutant strain thereof, from the viewpoint of exhibiting the effects of the present invention more remarkably.
  • Bacteria belonging to the genus Shewanella belong to the family Shewanellaceae, and are Gram-negative, non-spore-forming anaerobic bacilli that are mainly distributed in the marine environment, and include barophilic bacteria, psychrophilic bacteria, and the like that live in the deep sea and the like.
  • a "mutant strain" of a specific species refers to a strain in which a mutation has occurred in the DNA possessed by the original strain of the species.
  • the mutation is not particularly limited, and may be, for example, base substitution, deletion, insertion, duplication, translocation or inversion in genomic DNA or a plasmid originally carried by the strain. Mutations may be naturally occurring or artificially occurring.
  • Shewanella bacterium or its mutant may further contain naturally-derived or artificial DNA such as plasmids and bacterial artificial chromosomes (BAC) in addition to genomic DNA.
  • naturally-derived or artificial DNA such as plasmids and bacterial artificial chromosomes (BAC) in addition to genomic DNA.
  • BAC bacterial artificial chromosomes
  • the genome sequence of the mutant is, for example, 90% or more, 95% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, 99.9% or more of the reference genome sequence of the organism. , has a sequence identity of greater than or equal to 99.99% or greater than or equal to 99.999%.
  • Shewanella bacteria examples include Shewanella woodyi, Shewanella electrodiphila, S. marintestina, S. schlegeliana, and Shewanella cylae. (S. sairae), S. pealeana, S. hanedai, S. gelidimarina, S. pneumatophore, Shewanella baltica (S. baltica), S. halifaxensis, S. kaireitica, S. glacialipiscicola, S. fidelis, Shewanella aquimarina (S. aquimarina), S. waksmanii, S. marisflavi, S. affinis, S. colwelliana, S.
  • Shewanella bacterium is preferably Shewanella woodyi, more preferably Shewanella woodyi GS001 strain.
  • Shewanella udii See, for example, Brenner et al. (The Proteobacteria, 2005, p.480-491), Zhao et al. (Int. J. Syst. Evol Microbiol., 2005, Vol. 55, p. 1511-1520), Makemson, J.C. et al. (Int. J. Syst. Bacteriol., 1997, Vol.47, Issue 4, p.1034-1039), Ivanova et al. (Int. J. Syst. Evol. Microbiol. 2003, Vol.53, p.577-582).
  • the sequence identity of the 16S rDNA sequence thereof to the 16S rDNA sequence (SEQ ID NO: 1) of the following Shewanella oudii strain GS001 is preferably 95% or more, more preferably 96% or more, and 97%. 98% or more is more preferable, and 99% or more is particularly preferable.
  • the identity of the 16S rDNA sequence is determined using Align two or more sequences in blastn (for base sequences) of BLAST (https://blast.ncbi.nlm.nih.gov/) of NCBI. It is the percentage of "Identities" obtained by inputting a sequence to compare a specific sequence to Query Sequence and performing alignment with default parameters.
  • the Shewanella udii strain GS001 (hereinafter sometimes referred to as "GS001 strain") is a strain isolated from the intestinal tract of Nigisu, a deep-sea fish.
  • the 16S rDNA sequence of strain GS001 is shown in SEQ ID NO:1.
  • the GS001 strain is characterized by being able to grow well using glucose as the sole carbon source.
  • the GS001 strain was cultured with shaking (150 rpm) at 15°C using a 100 mL flask containing 50 mL of a modified M9 liquid medium containing 10% (w/v) glucose (modified M9 + Glc liquid medium) for 48 hours.
  • OD600nm can grow to a cell density of 5 or more.
  • the GS001 strain is characterized by being able to grow well in a semi-synthetic medium containing glucose and yeast extract.
  • the GS001 strain is aerated cultured at 15 ° C.
  • the dry cell weight can grow to 35 g/L or more in 75 hours.
  • the GS001 strain is characterized by a high EPA content.
  • the GS001 strain was aerated at 15° C. (1 vvm air, 150-750 rpm) using a 3 L jar fermenter containing 2 L of modified M9+Glc liquid medium containing 0.5% (w/v) yeast extract. At times, the EPA content per dry cell weight can be maintained above 0.5 g/100 g dry cell weight.
  • the GS001 strain is characterized by being able to grow in sodium chloride concentrations as low as 0.5% (w/v).
  • the GS001 strain was cultured with shaking (150 rpm) at 15 ° C. using a 100 mL flask containing 50 mL of modified M9 + Glc medium with a sodium chloride concentration of 0.5% (w / v). can grow to a density of 3 or more.
  • the GS001 strain was granted accession number NITE P-03460 on April 15, 2021 at the Patent Microorganism Depositary Center, National Institute of Technology and Evaluation (zip code 292-0818, 2-Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan). 5-8 Room 122).
  • the GS001 strain is identified as Shewanella woodyi, accession number NITE BP-03460, and is registered at the Patent Microorganism Depositary Center, National Institute of Technology and Evaluation (zip code 292-0818, 2-5 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan). 8 122) under the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure (National Deposit Date April 15, 2021; Request for Transfer to International Deposit Date April 4, 2022 Day).
  • the genus Shewanella or its mutants contain the phospholipid of formula (I) at a high intracellular content. Therefore, an extract of the genus Shewanella or a mutant strain thereof can be suitably used in the oral composition of the present invention. And, since the Shewanella udii GS001 strain has the characteristics described above, it is particularly suitable for industrial production of the phospholipid of the formula (I).
  • Shewanella and their mutant strains can be cultured using media commonly used for culturing heterotrophic bacteria. Culture conditions are not particularly limited as long as Shewanella bacteria can grow. ), and Shewanella electrodyphila can be set based on the description in Zhang J. et al. (PLoS One, 2017, Vol.12, No.11:e0188081).
  • the extract of the genus Shewanella or its mutants is not particularly limited as long as it is an extract of cell components, for example, a cell disruption obtained by disrupting cells, a cell lysate obtained by lysing cells, or any of them may be a solvent extract obtained by solvent extraction from Among them, the extract of the genus Shewanella or its mutant is preferably a solvent extract from the viewpoint of improving the absorbability of the active ingredient into the body.
  • the solvent used in the preparation of the solvent extract is not particularly limited as long as it can be used in an oral composition that can be ingested or administered, and is appropriately selected depending on the form of the oral composition (medicine, food and drink, etc.). can choose. Alcohol, for example, is preferred as the solvent.
  • the extraction of the phospholipid of the formula (I) from Shewanella bacteria or mutants thereof can be carried out by known methods.
  • cells are recovered from the culture medium of the bacterium of the genus Shewanella or its mutant strain by centrifugation, filtration, or the like, and all lipids are extracted from the cells with the above solvent.
  • the amount of extraction solvent used for cells is not particularly limited.
  • the amount of extraction solvent can be, for example, about 1 to 1000 times (preferably about 5 to 200 times) the amount of cells.
  • the extraction operation can usually be carried out under normal pressure in the range from room temperature to the boiling point of the solvent. The extraction operation may be performed only once or may be performed multiple times.
  • a fresh extraction solvent may be added again to the cell residue that has been subjected to the extraction operation once, or the extraction operation may be performed again.
  • cell debris may be removed by centrifugation, filtration, ultrafiltration, or the like.
  • the extraction solvent may be removed by heating or distillation under reduced pressure using an evaporator or the like.
  • various purification treatments may be performed to purify the phospholipids.
  • Purification treatments include, for example, salting out, dialysis, recrystallization, reprecipitation, solvent extraction, adsorption, concentration, filtration, gel filtration, ultrafiltration, various chromatography (thin layer chromatography, column chromatography, ion exchange chromatography, high-performance liquid chromatography, adsorption chromatography, etc.), but are not limited thereto.
  • the oral composition of the present invention is orally ingested or administered. ), pharmaceuticals, quasi-drugs, feeds or feeds, or preparations for their manufacture (eg, additives).
  • the oral composition of the present invention is a drug or quasi-drug
  • its forms include, for example, liquids, tablets, powders, granules, capsules, powders, lozenges, syrups and the like.
  • composition for oral use of the present invention is a food or drink
  • its form includes, for example, sweets (caramel, candy, etc.), frozen desserts (ice cream, etc.), dairy products (yogurt, etc.), various processed foods, various seasonings. foods, various beverages, functional foods, dietary supplements, and supplements.
  • composition for oral use of the present invention is in the form of a drug or quasi-drug, or a formulation for manufacturing thereof
  • other ingredients include, for example, pharmaceutically acceptable carriers (excipients, disintegrants, binders , lubricants, colorants, plasticizers, antioxidants, pH adjusters, thickeners, surfactants, stabilizers, preservatives, perfumes, fluidizers, liquid media, foaming agents, etc.) Any one or a combination of two or more selected from, but not limited to, these.
  • composition for oral use of the present invention is in the form of a food or drink, a feed or feed, or a formulation for producing them
  • other ingredients include, for example, fish meat, vegetables, grains, dairy products, fermented products, spices, and proteins. , amino acids, sugars, various seasonings, sweeteners, flavoring agents, flavors, oils and fats, vitamins, thickeners, gelling agents, antioxidants, preservatives, chelating agents, pH adjusters, colorants Any one or a combination of two or more selected from, but not limited to, these.
  • glycerol-1-phosphate moieties CH 2 OH-CHOH-CH 2 -OPO
  • EPA-bound glycerol-1-phosphate-type phospholipids EPA-bound ethanolamine-type phospholipids. 2 - -
  • ethanolamine phosphate moieties NH 3 + -CH 2 -CH 2 -OPO 2 - -
  • composition for oral use of the present invention contains an effective amount of the above-mentioned active ingredient, so that, for example, the effect of increasing muscle; action to suppress the rise of; action to suppress fat accumulation in the liver; action to increase omega-3 fatty acids (especially eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid) in the body (e.g., liver) and omega-6 fatty acids (especially, arachidonic acid); reducing blood triglycerides, total cholesterol, LDL cholesterol and non-HDL cholesterol; and reducing the amount of white adipose tissue.
  • active ingredient e.g., the effect of increasing muscle; action to suppress the rise of; action to suppress fat accumulation in the liver; action to increase omega-3 fatty acids (especially eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid) in the body (e.g., liver) and omega
  • composition for oral use of the present invention are remarkably higher than krill oil containing a large amount of phosphatidylcholine containing docosahexaenoic acid and eicosapentaenoic acid as fatty acids.
  • the oral composition of the present invention increases omega-3 fatty acids as described above, it can be used to increase omega-3 fatty acids in the body (for example, liver).
  • the omega-3 fatty acid is preferably at least one selected from docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA), more preferably DHA.
  • omega-3 fatty acids As used herein, “improving the balance between omega-3 fatty acids and omega-6 fatty acids” means increasing the ratio of omega-3 fatty acids to omega-6 fatty acids in total lipids in the body (for example, liver).
  • Omega-6 fatty acids include, for example, arachidonic acid (AA), linoleic acid, ⁇ -linolenic acid, dihomo ⁇ -linolenic acid, docosatetraenoic acid and 22:5n-6 docosapentaenoic acid (ospondonic acid).
  • omega-3 fatty acids examples include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), 22:5n-3 docosapentaenoic acid (clupanodonic acid, DPA), ⁇ -linolenic acid, stearidonic acid and eicosatetra. enoic acid.
  • omega-6 fatty acids are metabolized to pro-inflammatory lipid mediators and omega-3 fatty acids are metabolized to anti-inflammatory lipid mediators. , leading to the prevention or amelioration of inflammation in the body. Therefore, the oral composition of the present invention also has an effect of preventing or improving inflammation.
  • the oral composition of the present invention also exerts an effect of preventing or ameliorating conditions, symptoms or diseases associated with decreased muscle or muscle strength, such as locomotive syndrome and sarcopenia, through its action of increasing muscle mass.
  • the composition for oral use of the present invention through the action of increasing muscle, the action of suppressing the rise of blood sugar level, the action of suppressing the accumulation of fat in the liver, and the action of suppressing the increase of white adipose tissue, is effective against lifestyle-related diseases or metabolic syndrome. There is also an effect of prevention or improvement of
  • the oral composition of the present invention increases muscle or muscle strength, suppresses muscle or muscle strength loss, improves glucose metabolism (for example, improves blood sugar level, more specifically, at least one selected from the group consisting of improvement of hyperglycemia, improvement of postprandial blood sugar level, improvement of average blood sugar level or HbA1c level, etc.), suppression of fat accumulation in the liver, and improvement of the balance of omega-3 fatty acids and omega-6 fatty acids in the body It can be used for one species.
  • the composition for oral use of the present invention includes at least one selected from the group consisting of diabetes, fatty liver (non-alcoholic fatty liver or alcoholic fatty liver), inflammation, locomotive syndrome, sarcopenia, lifestyle-related diseases and metabolic syndrome. can be used for the prevention or improvement of
  • composition for oral use of the present invention is further selected from the group consisting of improving blood lipid status (for example, improving blood neutral fat (triglyceride) level, cholesterol level or LDL cholesterol level, etc.) and promoting weight loss.
  • improving blood lipid status for example, improving blood neutral fat (triglyceride) level, cholesterol level or LDL cholesterol level, etc.
  • promoting weight loss can also be used for at least one
  • the oral composition of the present invention is also used for the prevention or improvement of at least one selected from the group consisting of dyslipidemia (e.g., hypertriglyceridemia, hyperLDL cholesterolemia), arteriosclerosis and obesity. can be used.
  • dyslipidemia e.g., hypertriglyceridemia, hyperLDL cholesterolemia
  • arteriosclerosis e.g., arteriosclerosis and obesity.
  • the oral composition of the present invention can be used therapeutically or non-therapeutically.
  • non-therapeutic means not including medical practice, for example, not including surgery, treatment or diagnosis of humans by a doctor or those under the direction of a doctor.
  • the oral composition of the present invention has the effect of maintaining or promoting the expression of the ELOVL2, ELOVL5, FADS1 or FADS2 gene in the liver of a subject, as shown in the Examples. Therefore, the oral composition of the present invention can be used to maintain or promote ELOVL2, ELOVL5, FADS1 or FADS2 gene expression (eg, mRNA expression) in the body (preferably in the liver).
  • ELOVL2 (Fatty Acid Elongase 2) and ELOVL5 (Fatty Acid Elongase 5) are genes encoding enzymes that catalyze chain elongation of unsaturated fatty acids.
  • FADS1 (Fatty Acid Desaturase 1)
  • FADS2 (Fatty Acid Desaturase 2) are genes encoding enzymes that introduce double bonds into fatty acids. These genes are involved in the synthesis of polyunsaturated fatty acids (PUFA) such as EPA, DHA and DPA.
  • PUFA polyunsaturated fatty acids
  • the oral composition of the present invention unlike krill oil and other oils containing polyunsaturated fatty acids of a different type than the present invention, inhibits the expression of these genes in the liver.
  • the oral composition of the present invention may be a composition indicating the above uses as efficacy or function.
  • Such indications include, for example, direct indications of the above uses or indications that substantially imply the above uses.
  • Examples of direct indications for the above uses include “maintenance of muscle/strength” and “keep muscle” as examples of indications for suppressing muscle or muscle strength loss; “Slows blood sugar level”, “Lowers blood sugar level”, “Reduces high blood sugar level to normal”, “Slows postprandial rise in blood sugar level”, “Reduces postprandial blood sugar level “Reduce blood sugar rise”, “Reduce postprandial blood sugar level”, “Reduce high fasting blood sugar level to normal”, “Lower blood sugar”, etc.; “reduce visceral fat”, “reduce visceral fat accumulation”, “reduce liver fat”, “reduce visceral fat”, “reduce belly fat”, etc., but are not limited to these.
  • indications that substantially indicate the above uses include, for example, figurative indications of the above uses, indications of subjects for which intake or administration is recommended, and indications that they act on specific diseases, symptoms, or health conditions. etc.
  • indications include “for those who are concerned about muscle weakness,” “muscle/strength support,” “muscle storage,” “blood sugar care,” “blood sugar support,” and “for those who are concerned about blood sugar levels.”
  • blood sugar countermeasures “those who are concerned about belly fat”, “refreshing around the stomach”, “anti-inflammatory”, “metabolite countermeasures”, “locomo countermeasures", “lifestyle disease countermeasures”, etc. include but are not limited to:
  • Subjects to which the oral composition of the present invention is ingested or administered are humans or non-human animals (e.g. mammals other than humans), preferably diabetes, fatty liver, inflammation, locomotive syndrome, sarcopenia or metabolic syndrome. or at risk of having those diseases, conditions or conditions.
  • the target age is not particularly limited, but it applies to adults, for example.
  • the dosage or intake of the oral composition of the present invention is appropriately determined according to the body weight, sex, age, condition, or other factors of the subject of administration or intake.
  • the dosage or intake of the oral composition of the present invention is, for example, 0 as the total amount of the phosphorylated ethanolamine moiety, the glycerol-1-phosphate moiety and the eicosapentaenoic acid moiety per day. .1-1,000 mg/kg body weight, 0.5-500 mg/kg body weight or 1-100 mg/kg body weight.
  • Oral compositions of the invention are administered or taken, for example, 1 to 5, 1 to 3, or 2 to 3 times daily.
  • SW oil Shewanella udii GS001 strain extract
  • a Shewanella udii GS001 strain extract (hereinafter sometimes referred to as SW oil) was prepared by the following procedure. (1) Cells collected from a culture of Shewanella udii strain GS001 were dried. (2) Lipids were extracted from the dried microbial cells using alcohol. (3) The extract was filtered and the filtrate was further concentrated. (4) Separation operation was performed using hexane, the hexane fraction was separated and concentrated, and the precipitate was dried to obtain SW oil.
  • SE oil Shewanella electrodyphila extract
  • ⁇ Krill oil fish oil> Krill oil contains mainly phosphatidylcholine (PC) as phospholipid and little PE and PG.
  • PC phosphatidylcholine
  • a commercial product from Aker BioMarine was used.
  • a fish oil commercially available from Maruha Nichiro Co., Ltd. was used.
  • Soybean oil, lard> Soybean oil used was Fuji Film Wako Pure Chemical Co., Ltd., and lard was used commercially available from Junsei Chemical Co., Ltd.
  • Table 1 shows the contents of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), ethanolamine-type phospholipid (PE), and glycerol-1-phosphate-type phospholipid (PG) in SW oil and krill oil. Ta.
  • the contents of EPA and DHA represent the total amount of free fatty acids and those contained as acyl groups in triglycerides, phospholipids, and the like.
  • SW oil does not contain DHA.
  • Total lipids were extracted from dried cells of Shewanella electrodyphila by the following procedure, and polar lipids were further fractionated.
  • the content of phospholipid-type EPA relative to the total amount of EPA in the lipid obtained from the dried cells was 61.3% by mass
  • the content of neutral lipid-type EPA was 32.6% by mass
  • the content of glycolipid-type EPA was The amount was 6.1% by weight.
  • PG was 32.4% by mass
  • PE was 59.7% by mass with respect to the total amount of phospholipids in the lipids obtained from the dried cells.
  • the PE and PG fractions were peeled off from the TLC plate, transferred into a glass column, and each lipid was eluted with 50 mL of methanol. Thereafter, methanol was distilled off using an evaporator to obtain PE and PG.
  • Table 2 shows the fatty acid composition analysis results in the total lipids of SE oil, fish oil, and krill oil.
  • Feed was given ad libitum from the 0th to 8th days after the start of rearing, and from the 9th day onwards, feeding was restricted according to the food intake of the SW oil group (Fig. 3). Water was given ad libitum. There was no significant difference in body weight transition of mice between groups during the study.
  • the blood glucose level was measured by incising the vein at the tip of the tail of the mouse with a scalpel under no anesthesia, and measuring the blood leaking from the incised surface with a blood glucose measuring device (Statstrip Express Glucose Ketone, manufactured by Nova Biomedical Co., Ltd.). The blood glucose was sucked into the connected blood glucose measuring chip and measured.
  • a blood glucose measuring device Statstrip Express Glucose Ketone, manufactured by Nova Biomedical Co., Ltd.
  • the blood glucose was sucked into the connected blood glucose measuring chip and measured.
  • 20 ⁇ L of the blood obtained by the above whole blood collection was aliquoted and stored at ⁇ 70° C. or below.
  • a DCA bandage manufactured by SIEMENS
  • adipose tissue weight White adipose tissue was removed from each group of mice after feeding for 6 weeks, and the weight of the perirenal/retroabdominal fat and all of the white adipose tissue was measured.
  • PUFA polyunsaturated fatty acid
  • FIG. 4 shows the results of comparing the gastrocnemius muscle weights of the mice in each group.
  • the SW oil group significantly increased the gastrocnemius muscle weight compared to the control group, whereas no significant difference was observed between the low dose krill oil group and the high dose krill oil group.
  • FIG. 5A The fasting blood sugar level on the 41st day is shown in FIG. 5A, and the blood sugar level and HbA1c after 2 hours of feeding on the 42nd day are shown in FIGS. 5B and 5C.
  • the blood sugar level was suppressed significantly lower in the SW oil group than in the control group and the two groups administered with krill oil.
  • the HbA1c value was also significantly lower in the SW oil group than in the control group and the two groups to which krill oil was administered.
  • FIG. 6 shows the results of comparing the liver weights of the mice in each group after completing feeding for 6 weeks.
  • the SW oil group did not show a significant difference from the control group, but the two groups administered krill oil showed a significant increase in liver weight compared to the control group. It is speculated that the phospholipids contained in krill oil induced fat accumulation in the liver.
  • FIGS. 7A and 7B The evaluation results of blood triglyceride and cholesterol are shown in FIGS. 7A and 7B.
  • the SW oil group had significantly lower blood triglycerides, total cholesterol, LDL cholesterol and non-HDL cholesterol levels than the control group.
  • FIG. 8 shows the results of comparing the adipose tissue weights of the mice of each group after completing feeding for 6 weeks.
  • the total amount of white adipose tissue and the weight of perirenal and posterior abdominal wall fat were significantly lower than in the control group.
  • FIG. 9 shows the n-3 PUFA composition in the liver of each group of mice after feeding for 6 weeks.
  • the SW oil group showed a significant increase in the amount of EPA (20:5n-3) accumulated in the liver compared to the control group, and a significant increase in its proportion in the fatty acid composition was also observed.
  • DHA 22:6n-3)
  • DPA docosapentaenoic acid
  • the krill oil group although the krill oil contains a relatively large amount of DHA, an increase in the amount of DHA accumulated in the liver and the proportion of DHA in the fatty acid composition was not observed. Also, no significant increase in DPA in the liver was observed.
  • the Shewanella bacterium extract has (i) an effect of increasing muscle mass or an effect of suppressing muscle loss, (ii) fasting blood sugar level, postprandial blood sugar level, and average blood sugar level reflected by HbA1c (iii) suppressing fat accumulation in the liver, (iv) suppressing increases in total cholesterol, LDL cholesterol and non-HDL cholesterol, and improving the state of blood lipids. (v) an effect of suppressing an increase in the amount of white adipose tissue; and (vi) an effect of increasing EPA, DPA and DHA in the liver.
  • a comparison of the effects of the SW oil group and the low dose krill oil group shows that these effects are due to EPA-bound ethanolamine-type phospholipids and EPA-bound glycerol-type phospholipids.
  • G1 control group
  • G2 low dose SE oil group (Shewanella-L)
  • G3 High dose SE oil group (Shewanella-H)
  • G4 low dose fish oil group (Fish-L)
  • G5 High dose fish oil group: (Fish-H)
  • G6 Low dose krill oil group (Krill-L)
  • G7 high dose krill oil group (Krill-H)
  • mice in each group were bred by freely ingesting the feed and water having the composition shown in Table 4 for 4 weeks. After the breeding period ended, the liver was removed from the mouse.
  • Shewanella genus extract has the effect of significantly increasing the ratio of omega-3 fatty acids to omega-6 fatty acids.
  • this effect is also due to EPA-bound ethanolamine-type phospholipids and EPA-bound glycerol-type phospholipids.
  • Figures 11A to 11D show the results of quantifying the amount of mRNA for each gene.
  • Shewanella extract was given to mice, the expression of ELOVL2 was significantly promoted compared to the control group, and the expression levels of ELOVL5, FADS1 and FADS2 tended to be maintained or promoted.
  • krill oil was given to mice, it was found that the expression levels of ELOVL2, ELOVL5, FADS1 and FADS2 in the liver were significantly reduced.

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Abstract

La présente invention aborde le problème de la fourniture d'un nouvel ingrédient fonctionnel lipidique qui peut être pris ou administré par voie orale. Un exemple d'une composition contenant ledit ingrédient est une composition contenant des fractions de glycérol-1-phosphate (CH2OH-CHOH-CH2-OPO2 --), des fractions de phosphate d'éthanolamine (NH3 +-CH2-CH2-OPO2 --) et des fractions d'acide eicosapentaénoïque CH3CH2(CH=CHCH2)5(CH2)2CO-), le rapport molaire des fractions de phosphate d'éthanolamine aux fractions de glycérol-1-phosphate étant de 0,01 à 100.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000245442A (ja) * 1999-02-24 2000-09-12 Sagami Chem Res Center イコサペンタエン酸を産生する微生物及びイコサペンタエン酸の製造方法
WO2015005466A1 (fr) * 2013-07-12 2015-01-15 国立大学法人京都大学 Procédé de production de lipides ayant une haute teneur en acide eicosapentaénoïque
WO2019208392A1 (fr) * 2018-04-27 2019-10-31 株式会社レオロジー機能食品研究所 Nouveau dérivé de plasmalogène
WO2022255477A1 (fr) * 2021-06-04 2022-12-08 Dic株式会社 Bactéries shewanella et leur utilisation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000245442A (ja) * 1999-02-24 2000-09-12 Sagami Chem Res Center イコサペンタエン酸を産生する微生物及びイコサペンタエン酸の製造方法
WO2015005466A1 (fr) * 2013-07-12 2015-01-15 国立大学法人京都大学 Procédé de production de lipides ayant une haute teneur en acide eicosapentaénoïque
WO2019208392A1 (fr) * 2018-04-27 2019-10-31 株式会社レオロジー機能食品研究所 Nouveau dérivé de plasmalogène
WO2022255477A1 (fr) * 2021-06-04 2022-12-08 Dic株式会社 Bactéries shewanella et leur utilisation

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
KAWAMOTO JUN, KURIHARA TATSUO, YAMAMOTO KENTARO, NAGAYASU MAKIKO, TANI YASUSHI, MIHARA HISAAKI, HOSOKAWA MASASHI, BABA TAKESHI, SA: "Eicosapentaenoic Acid Plays a Beneficial Role in Membrane Organization and Cell Division of a Cold-Adapted Bacterium, Shewanella livingstonensis Ac10", JOURNAL OF BACTERIOLOGY, AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 191, no. 2, 15 January 2009 (2009-01-15), US , pages 632 - 640, XP093086855, ISSN: 0021-9193, DOI: 10.1128/JB.00881-08 *
SATO SHO, KAWAMOTO JUN, SATO SATOSHI B., WATANABE BUNTA, HIRATAKE JUN, ESAKI NOBUYOSHI, KURIHARA TATSUO: "Occurrence of a Bacterial Membrane Microdomain at the Cell Division Site Enriched in Phospholipids with Polyunsaturated Hydrocarbon Chains", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 287, no. 29, 1 July 2012 (2012-07-01), US , pages 24113 - 24121, XP093086857, ISSN: 0021-9258, DOI: 10.1074/jbc.M111.318311 *
SI ZHU, MENGWEI YE, JILIN XU, CHUNYANG GUO, HUAKUN ZHENG, JIABAO HU, JUANJUAN CHEN, YAJUN WANG, SHANLIANG XU, XIAOJUN YAN: "Lipid Profile in Different Parts of Edible Jellyfish Rhopilema esculentum", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 63, no. 37, 23 September 2015 (2015-09-23), US , pages 8283 - 8291, XP055607349, ISSN: 0021-8561, DOI: 10.1021/acs.jafc.5b03145 *

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