WO2018155525A1 - 抗炎症剤 - Google Patents

抗炎症剤 Download PDF

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Publication number
WO2018155525A1
WO2018155525A1 PCT/JP2018/006351 JP2018006351W WO2018155525A1 WO 2018155525 A1 WO2018155525 A1 WO 2018155525A1 JP 2018006351 W JP2018006351 W JP 2018006351W WO 2018155525 A1 WO2018155525 A1 WO 2018155525A1
Authority
WO
WIPO (PCT)
Prior art keywords
liver hydrolyzate
production
liver
inflammatory
hydrolyzate
Prior art date
Application number
PCT/JP2018/006351
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
耕太郎 山田
英知 櫻井
三千夫 駒井
仁 白川
圭佑 中村
プスポ エディ ギリウノ
一馬 植田
Original Assignee
ゼリア新薬工業株式会社
国立大学法人東北大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ゼリア新薬工業株式会社, 国立大学法人東北大学 filed Critical ゼリア新薬工業株式会社
Priority to JP2019501395A priority Critical patent/JP7216966B2/ja
Priority to CN201880007881.6A priority patent/CN110198723B/zh
Priority to SG11201907124YA priority patent/SG11201907124YA/en
Priority to KR1020197023135A priority patent/KR102608239B1/ko
Publication of WO2018155525A1 publication Critical patent/WO2018155525A1/ja

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Classifications

    • 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
    • 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
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A23L33/28—Substances of animal origin, e.g. gelatin or collagen
    • 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
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/37—Digestive system
    • A61K35/407—Liver; Hepatocytes
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/204—Animal extracts

Definitions

  • the present invention relates to a highly safe anti-inflammatory agent.
  • Non-patent Document 2 the antibody drug tricizumab is used (Non-patent Document 2). Furthermore, protein preparations and antibody drugs such as anakinra, rilonacept, and canakinumab have been developed as IL-1 inhibitors (Non-patent Document 3).
  • an object of the present invention is to provide a novel anti-inflammatory agent based on the inhibition of inflammatory cytokines which is highly safe and can be widely used.
  • the present inventor has examined the action on the production of inflammatory cytokines using various components.
  • liver hydrolysates that have been widely used for improvement of liver function, improvement of hangover in chronic liver disease, etc. Since it has a strong IL-1 production inhibitory action, it has been found that it is useful as an anti-inflammatory agent by suppressing the production of inflammatory cytokines.
  • the present invention provides the following [1] to [15].
  • An anti-inflammatory agent comprising liver hydrolyzate as an active ingredient.
  • An inflammatory cytokine production inhibitor comprising liver hydrolyzate as an active ingredient.
  • An IL-1 production inhibitor comprising liver hydrolyzate as an active ingredient.
  • a food composition for improving inflammation comprising liver hydrolyzate as an active ingredient.
  • a food composition for suppressing inflammatory cytokine production comprising liver hydrolyzate as an active ingredient.
  • a food composition for inhibiting IL-1 production comprising liver hydrolyzate as an active ingredient.
  • Use of liver hydrolyzate for the production of an anti-inflammatory agent Use of a liver hydrolyzate for producing an inflammatory cytokine production inhibitor.
  • liver hydrolyzate for producing an IL-1 production inhibitor.
  • a liver hydrolyzate for treating inflammatory diseases comprising administering an effective amount of a liver hydrolyzate.
  • a liver hydrolyzate for suppressing IL-1 production comprising administering an effective amount of a liver hydrolyzate.
  • a method for suppressing the production of inflammatory cytokines comprising administering an effective amount of liver hydrolyzate.
  • a method for inhibiting IL-1 production comprising administering an effective amount of a hydrolyzate of liver.
  • liver hydrolyzate has a strong inhibitory effect on IL-1 production, and therefore suppresses the production of inflammatory cytokines and is useful as an anti-inflammatory agent.
  • liver hydrolyzate can be administered orally, has few side effects, and is excellent in safety and usability, so it can also be used as a food composition.
  • liver hydrolyzate also called liver hydrolyzate, liver extract, liver decomposed extract, or liver hydrolyzate
  • liver hydrolyzate is obtained by hydrolyzing the liver with digestive enzymes etc., and is used as a liver function improving drug Is.
  • the liver which is a raw material, fresh livers such as cows, pigs, bonito and whales are used.
  • the obtained hydrolyzate is preferably used after being concentrated.
  • liver hydrolyzate defined as the pharmaceutical product is used.
  • Liver hydrolyzate contains various amino acids, nucleotides, vitamins, minerals, etc., mainly composed of low molecular weight peptides. More specifically, amino acids 19 to 78% by mass, peptides and proteins 17 to 73% by mass, sugars 1.8 to 11% by mass, lipids 0.005 to 0.04% by mass, and nucleic acids 0.7 to 2.5% by mass. %, Inorganic substances 1.6 to 5.4% by mass, vitamins 0.03 to 0.2% by mass, and glutathione 0.8% by mass or less are preferable.
  • the amino acid composition is Ala 17 to 68 mg / g, Arg 0.6 to 4.4 mg / g, Asp 9 to 48 mg / g, Cystein 5 mg / g or less, Glu 18 to 63 mg / g, Gly 10-39 mg / g, His 3-17 mg / g, Ile 14-56 mg / g, Leu 26-98 mg / g, Lys 15-65 mg / g, Met 0.3-20 mg / g, Phe 13-46 mg / g, Pro 10-48 mg / g, Ser 12-49 mg / g, Thr 12-45 mg / g, Trp 3-13 mg / g, Tyr 1.6-41 mg / g, Val 18-71 mg / g are preferred.
  • a low molecular weight fraction of liver hydrolyzate can also be used.
  • a fraction having a molecular weight of 3000 or less for example, a fraction obtained by collecting a fraction having a molecular weight of 3000 or less from the liver hydrolyzate using an ultrafiltration membrane or the like can be used.
  • liver hydrolyzate and low molecular weight fraction thereof have an action of strongly suppressing the production of IL-1 ⁇ , which is a kind of inflammatory cytokine, and an action of suppressing the expression of IL-1 ⁇ mRNA. . Therefore, the liver hydrolyzate suppresses the production of inflammatory cytokines typified by IL-1, and is useful as a therapeutic agent for inflammatory diseases involving inflammatory cytokines and a food and drink composition for improving inflammation.
  • diseases involving inflammatory cytokines include rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, sepsis, acute and chronic myelogenous leukemia, osteoporosis, lifestyle-related diseases and the like.
  • the anti-inflammatory agent of the present invention can be administered by oral administration, transdermal administration, enteral administration, intravenous administration, etc., and oral administration is more preferred.
  • oral administration examples include liquids, tablets, powders, fine granules, granules, capsules and the like, but liquids and tablets are preferable, and liquids are more preferable.
  • preparations for oral administration include excipients such as lactose, mannitol, corn starch and crystalline cellulose, cellulose derivatives, binders such as gum arabic and gelatin, disintegrants such as carboxymethylcellulose calcium, talc, magnesium stearate And the like, solubilizers such as nonionic surfactants, flavoring agents, sweeteners, stabilizers, pH adjusters, water, ethanol, propylene glycol, glycerin and the like can be used. Further, a coating agent such as hydroxymethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate, and methacrylate copolymer may be used.
  • excipients such as lactose, mannitol, corn starch and crystalline cellulose, cellulose derivatives, binders such as gum arabic and gelatin, disintegrants such as carboxymethylcellulose calcium, talc, magnesium stearate And the like, solubilizers such as non
  • active ingredients can also be mix
  • Other active ingredients vitamins B 1 class; thiamine, thiamine mononitrate, thiamine hydrochloride, fursultiamine, bisbentiamine, Benhochiamin, thiamine disulfide, dicethiamine, thiamine propyl disulfide, and derivatives thereof, vitamin B 2 compounds; riboflavin and derivatives and their salts, vitamin B 3 compound; niacin, nicotinic acid, nicotinamide and derivatives and salts thereof, vitamin B 5 like; panthenol, pantothenic acid and derivatives and salts thereof, vitamin B 6 such; pyridoxine and derivatives and their salts, vitamin B 12 compound; cyanocobalamin and derivatives and salts thereof, other vitamins vitamin a, vitamin C, vitamin E, vitamin K, vitamin P, dichloroacetate diisopropylamine, taurine, chondro Itine sulfate,
  • the anti-inflammatory agent of the present invention is highly safe and can be administered orally, in addition to pharmaceuticals, quasi-drugs, health functional foods, sports drinks, rehabilitation drinks, functional foods such as pet foods, etc. It can also be used as a food composition.
  • liver hydrolyzate in the anti-inflammatory agent of the present invention varies depending on the administration form, but is usually preferably 0.001 to 10% by mass, more preferably 0.001 to 5% by mass as a dry weight. Further, the daily dosage of liver hydrolyzate in the anti-inflammatory agent of the present invention is preferably 100 mg to 1076 mg, more preferably 383 mg to 623 mg, and further preferably 351 mg to 680 mg as a dry weight.
  • Test example 1 The number of RAW264.7 cells was adjusted to 1.5 ⁇ 10 6 cells / dish, seeded, and cultured overnight. Both the pre-fractionation sample or the filtrate fraction were diluted 20-fold with EMEM medium (final concentration about 0.6 mg / mL). As a control, PBS was diluted 20-fold with EMEM medium instead of the sample. Each sample (control, pre-fractionation, filtrate fraction) diluted with a medium was added to each dish group. After 24 hours of culture, lipopolysaccharide (LPS) was added to a final concentration of 1.0 ⁇ g / mL. The mixture was allowed to stand for 3 hours, RNA was collected, and cDNA was synthesized by reverse transcription. Next, EEF1A1 and IL-1 ⁇ were measured by RT-RCR.
  • LPS lipopolysaccharide
  • liver hydrolyzate has an anti-inflammatory effect, and a physiologically active substance exhibiting an anti-inflammatory effect is present in a low molecular fraction having a molecular weight of 3000 or less in the liver hydrolyzate.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nutrition Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Rheumatology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Pain & Pain Management (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Mycology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Physiology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/JP2018/006351 2017-02-23 2018-02-22 抗炎症剤 WO2018155525A1 (ja)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2019501395A JP7216966B2 (ja) 2017-02-23 2018-02-22 抗炎症剤
CN201880007881.6A CN110198723B (zh) 2017-02-23 2018-02-22 抗炎药
SG11201907124YA SG11201907124YA (en) 2017-02-23 2018-02-22 Anti-inflammatory agent
KR1020197023135A KR102608239B1 (ko) 2017-02-23 2018-02-22 항염증제

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2017-032541 2017-02-23
JP2017032541 2017-02-23

Publications (1)

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WO2018155525A1 true WO2018155525A1 (ja) 2018-08-30

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PCT/JP2018/006351 WO2018155525A1 (ja) 2017-02-23 2018-02-22 抗炎症剤

Country Status (6)

Country Link
JP (1) JP7216966B2 (ko)
KR (1) KR102608239B1 (ko)
CN (1) CN110198723B (ko)
SG (2) SG11201907124YA (ko)
TW (1) TWI794210B (ko)
WO (1) WO2018155525A1 (ko)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019208701A1 (ja) * 2018-04-26 2019-10-31 ゼリア新薬工業株式会社 ジペプチドを含有する医薬組成物

Citations (3)

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Publication number Priority date Publication date Assignee Title
JPH0578252A (ja) * 1991-04-26 1993-03-30 Sansho Seiyaku Co Ltd 安定なｓｏｄ活性を有する胎盤または肝臓抽出液およびそれを含有する外用剤組成物
JP2002080388A (ja) * 2000-09-04 2002-03-19 Takeda Food Products Ltd 肝機能賦活剤
WO2015046184A1 (ja) * 2013-09-25 2015-04-02 ゼリア新薬工業株式会社 肝臓機能及び／又は膵臓機能の改善剤

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Publication number Priority date Publication date Assignee Title
JPH0578252A (ja) * 1991-04-26 1993-03-30 Sansho Seiyaku Co Ltd 安定なｓｏｄ活性を有する胎盤または肝臓抽出液およびそれを含有する外用剤組成物
JP2002080388A (ja) * 2000-09-04 2002-03-19 Takeda Food Products Ltd 肝機能賦活剤
WO2015046184A1 (ja) * 2013-09-25 2015-04-02 ゼリア新薬工業株式会社 肝臓機能及び／又は膵臓機能の改善剤

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YANG, K. T. ET AL.: "Effects of chicken-liver hydrolysates on lipid metabolism in a high-fat diet", FOOD CHEM., vol. 160, 2014, pages 148 - 156, XP028660357 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019208701A1 (ja) * 2018-04-26 2019-10-31 ゼリア新薬工業株式会社 ジペプチドを含有する医薬組成物
JPWO2019208701A1 (ja) * 2018-04-26 2021-05-13 ゼリア新薬工業株式会社 ジペプチドを含有する医薬組成物

Also Published As

Publication number Publication date
TWI794210B (zh) 2023-03-01
TW201834670A (zh) 2018-10-01
SG11201907124YA (en) 2019-09-27
CN110198723B (zh) 2024-03-05
KR102608239B1 (ko) 2023-11-30
JPWO2018155525A1 (ja) 2019-12-12
CN110198723A (zh) 2019-09-03
SG10202108899XA (en) 2021-09-29
KR20190119039A (ko) 2019-10-21
JP7216966B2 (ja) 2023-02-02

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