WO2006104154A1 - Composition destinee a augmenter l'expression et l'activite d'une protease dans le foie - Google Patents

Composition destinee a augmenter l'expression et l'activite d'une protease dans le foie Download PDF

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Publication number
WO2006104154A1
WO2006104154A1 PCT/JP2006/306317 JP2006306317W WO2006104154A1 WO 2006104154 A1 WO2006104154 A1 WO 2006104154A1 JP 2006306317 W JP2006306317 W JP 2006306317W WO 2006104154 A1 WO2006104154 A1 WO 2006104154A1
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WO
WIPO (PCT)
Prior art keywords
liver
composition
protease
coenzyme
activity
Prior art date
Application number
PCT/JP2006/306317
Other languages
English (en)
Japanese (ja)
Inventor
Hiroshi Kubo
Hideyuki Kishida
Taizo Kawabe
Kazunori Hosoe
Original Assignee
Kaneka Corporation
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 Kaneka Corporation filed Critical Kaneka Corporation
Publication of WO2006104154A1 publication Critical patent/WO2006104154A1/fr

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Classifications

    • 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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A23L33/15—Vitamins
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • 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
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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

  • compositions that enhance the expression and activity of proteolytic enzymes in the liver
  • the present invention relates to expression and activity of a proteolytic enzyme in liver containing coenzyme Q as an active ingredient.
  • the present invention relates to a composition that enhances properties.
  • the liver is like a biological chemical factory, producing bile, regulating the metabolism of carbohydrates, proteins and fats, the three major nutrients' storage, decomposing waste and harmful substances' detoxification, hematopoiesis' regulating blood volume It is an important organ that takes on a wide variety of important functions that are vital to living bodies. The aforementioned functions are impaired due to virus infection, excessive intake of alcohol, drug addiction, disorder of eating habits, stress, smoking, etc., leading to diseases such as acute hepatitis, chronic hepatitis, alcoholic fatty liver and liver cancer. Conventionally, various drugs have been developed as preventive and therapeutic agents for such liver diseases.
  • Patent Documents 1, 2, 3, and 4 disclose certain proteolytic enzymes are effective as preventive and therapeutic agents for liver diseases.
  • Patent Documents 2 and 3 a very large amount of absorbed proteolytic enzyme is transferred to the liver, which is the site of injury, to induce and promote a healing reaction in the chronic inflammation of the liver, that is, degenerative degeneration and abnormal growth.
  • Patent Document 4 discloses that certain proteases are useful as drugs for liver diseases such as acute hepatitis, fulminant hepatitis, chronic hepatitis, and cirrhosis. From these facts, if the expression and activity of proteolytic enzymes in the liver can be increased by ingesting highly safe materials, it is considered useful for the prevention and treatment of liver diseases. However, no reports on such materials have been made so far.
  • Patent Document 1 Japanese Patent Laid-Open No. 7-75570
  • Patent Document 2 Japanese Patent Publication No. 1-56050
  • Patent Document 3 Japanese Patent Laid-Open No. 61-293927
  • Patent Document 4 JP-A-8-27026
  • an object of the present invention is to provide a highly safe composition that enhances the expression and activity of proteolytic enzymes in the liver.
  • the present invention also provides a reduced coenzyme Q represented by the above formula (1) and
  • a composition containing 10 as an active ingredient for enhancing the expression of proteolytic enzymes in the liver is provided.
  • Coenzyme Q as an active ingredient of the present invention
  • a composition for enhancing the expression and activity of a proteolytic enzyme in the liver containing 10 will be described.
  • Coenzyme Q which is an active ingredient in the composition for enhancing the activity of the protease in the liver of the present invention and the composition for enhancing the expression of the protease in the liver, is represented by the above formula (1) and
  • Equation (1) is reduced coenzyme Q
  • equation (2) is oxidized coenzyme Q.
  • the method for obtaining 10 is not particularly limited.
  • coenzyme Q can be obtained by a conventionally known method such as synthesis, fermentation, or extraction from a natural product.
  • a method of concentrating 10 categories can be adopted. Reduced coenzyme Q
  • a common reducing agent such as sodium borohydride or sodium dithionite (hydrosulfite sodium) is allowed to act.
  • composition for enhancing the activity of the protease in the liver of the present invention and the protease in the liver In a composition that enhances the expression of the enzyme, coenzyme Q is simply reduced or oxidized.
  • Coenzyme Q is a mixture of reduced and oxidized forms rather than oxidized forms alone
  • the lower limit is preferably 40% or more, more preferably 60% or more, more preferably 80% or more, more preferably 90% or more, more preferably 95% or more. Particularly preferred is 98% by weight or more.
  • the upper limit of reduced coenzyme Q is 100
  • the content of coenzyme Q in the composition for enhancing the activity of the protease in the liver and the composition for enhancing the expression of the protease in the liver of the present invention is 0.001 to 99% by weight.
  • the content is 0.01 to 20% by weight.
  • the content referred to here means the sum when the composition contains both oxidized and reduced forms.
  • the weight of coenzyme Q in this specification is measured using a high performance liquid chromatography (HPLC) system.
  • composition of the present invention can be used for pharmaceuticals, functional foods or food materials.
  • Functional food as used here means products intended to maintain or improve health by taking orally in addition to pharmaceuticals such as oral supplements, foods for specified health use, health foods, and nutritional supplements.
  • composition that enhances the activity of the protease in the liver and the composition that enhances the expression of the protease in the liver of the present invention is an acceptable carrier for coenzyme Q and pharmaceuticals or foods.
  • Carriers acceptable for pharmaceuticals or foods are not particularly limited. For example, excipients, disintegrants, lubricants, binders, coloring agents, anti-aggregation agents, absorption enhancers, solubilizers, stabilizers. Etc.
  • the dosage form of the composition of the present invention is not particularly limited.
  • the powder may be a liquid.
  • the liquid is not particularly limited, and examples thereof include drinks, injections, and infusions.
  • natural oils, oily higher fatty acids, higher fatty acid monodalysides, surfactants or mixtures thereof may be added and filled in oil to form soft capsules. In this case, those mainly composed of gelatin or other water-soluble polymer substances can be used.
  • Such capsules also include microcapsules.
  • the proteolytic enzyme in the liver is not particularly limited, and examples thereof include serine protease, thiol protease, and meta-mouth protease. Preferred are serine proteases and meta-oral proteases. Examples of serine proteases include trypsin, chymotrypsin, elastase and kallikrein, and examples of meta-oral proteases include carboxypeptidase.
  • composition for enhancing the activity of the protease in the liver and the composition for enhancing the expression of the protease in the liver of the present invention are, for example, other drugs such as liver for the prevention or treatment of liver diseases.
  • An antioxidant can also be added to the composition of the present invention.
  • Antioxidants that can be used at this time include citrate, citrate derivatives, vitamin C, vitamin C derivatives, lycopene, vitamin A, carotenoids, vitamin B, vitamin B derivatives, flavonoids, polyphenols, glutathione, Pillow mouth quinoline quinone, Pycnogenol, Frampangenol, Selenium, Sodium thiosulfate, Vitamin E, Vitamin E derivatives, Superoxide dismutase (SOD), Glutathione peroxidase, Glutathione S transphraglase, Glutathione reductase, Catalase, Ascorbic acid Peroxidase, and mixtures thereof.
  • SOD superoxide dismutase
  • Glutathione peroxidase Glutathione S transphraglase
  • Glutathione reductase Catalase
  • Ascorbic acid Peroxidase and mixtures thereof.
  • the composition for enhancing the activity of the protease in the liver and the composition for enhancing the expression of the protease in the liver of the present invention results in enhancing the expression and activity of the protease in the liver by administration.
  • Useful for treating or preventing liver disease include fatty liver, cirrhosis, primary biliary cirrhosis, primary sclerosing cholangitis. , Alpha 1-antitrypsin deficiency, acute hepatitis, chronic hepatitis, hepatocellular carcinoma, fulminant hepatitis, liver failure and the like.
  • preferred diseases include acute hepatitis, fulminant hepatitis, chronic hepatitis, and cirrhosis.
  • composition of the present invention increases the expression and activity of proteolytic enzymes in the liver, and is therefore useful for improving anorexia or increasing appetite.
  • the administration mentioned here is preferably enteral administration, particularly oral administration, including enteral and parenteral administration.
  • the dose of the composition of the present invention is not particularly limited. However, when administered to humans, it is preferably 10 to 1200 mg / day per adult, more preferably 30 to 60, in terms of fermenter Q.
  • Omg / ⁇ ⁇ more preferably 50 to 300 mgZ ⁇ .
  • Reduced coenzyme Q (provided that CE-2 (Nippon Claire Co., Ltd.)) is a feed for laboratory animals
  • Aging-promoting model mouse SAMP8 male, 4 weeks old, 6 purchased from Japan SLC Co., Ltd. were divided into 2 groups of 3 each so that the average body weight was equal, and the test group was reduced coenzyme Q
  • the containing diet was given to the control group and the control diet (CE-2) for 30 weeks.
  • RNAlater (Ambion) and stored frozen at ⁇ 80 ° C. until use. Extract total RNA from the liver of each individual, mix equal amounts of total RNA from 3 animals in the same group, Samples for analysis were used. A fluorescently labeled cDNA was prepared from the total RNA, which is an analysis sample, by a reverse transcriptase reaction. The cDNA derived from the test group was fluorescently labeled with Cy5, and the cDNA derived from the control group was fluorescently labeled with Cy3.
  • cDNAs were subjected to competitive hybridization on a DNA microarray (Agilent Mouse Oligo Microar ray, G4121A). Thereafter, the fluorescence intensity was measured using a scanner (Agilent's Agilent scanner), and the expression level of the proteolytic enzyme-related gene was analyzed.
  • the fluorescence intensity of Cy3 and Cy5 can be read for each gene by a scanner. From the obtained fluorescence intensity values, genes having a fluorescence intensity of 50 F.I. or higher were selected for both the test group and the control group, and the expression levels were compared between the test group and the control group. The expression level was compared by comparing the value of the fluorescence intensity of Cy5 divided by the fluorescence intensity of Cy3 for each gene, and if the value at that time was 2 or more, it was considered that the expression level was increased.
  • the number of fold changes obtained by dividing the fluorescence intensity of Cy5 by the fluorescence intensity of Cy3 (fold change) was 2 or more, and 19 genes were considered to have increased expression levels, of which 9 genes related to proteolytic enzymes were identified.
  • Table 1 shows. In the “Accession No.” column of the table, the identification number of each gene in GeneBank (NCBI nucleic acid sequence database) is used, and the “GO: molular functionj” and “Gu: biological processj” columns [here, Gene Ontology The category in which each gene is classified is described.
  • expression and activity of a proteolytic enzyme in the liver can be enhanced using a highly safe material.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention propose une composition très sure destinée à augmenter l'expression et l'activité d'une protéase dans le foie. Plus spécifiquement, elle propose une composition dont la matière active est la coenzyme Q10. Cette composition augmente l'expression et l'activité d'une protéase dans le foie.
PCT/JP2006/306317 2005-03-29 2006-03-28 Composition destinee a augmenter l'expression et l'activite d'une protease dans le foie WO2006104154A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005093729 2005-03-29
JP2005-093729 2005-03-29

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WO2006104154A1 true WO2006104154A1 (fr) 2006-10-05

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007034852A1 (fr) * 2005-09-22 2007-03-29 Kaneka Corporation Composition destinée à prolonger la vie et procédé destiné à prolonger la vie
WO2008069276A1 (fr) 2006-12-06 2008-06-12 Kaneka Corporation Agent thérapeutique contre le cancer et agent anti-carcinogène

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6118719A (ja) * 1984-07-06 1986-01-27 Kao Corp 胆石症治療剤
JPH02233611A (ja) * 1989-01-18 1990-09-17 Merck & Co Inc ＨＭＧ―ＣｏＡレダクターゼ阻害剤と併用される補酵素Ｑ↓１↓０
JPH09187229A (ja) * 1996-01-10 1997-07-22 Idemitsu Material Kk 家禽用飼料組成物
JPH10109933A (ja) * 1996-08-16 1998-04-28 Kanegafuchi Chem Ind Co Ltd 医薬組成物
JPH11199477A (ja) * 1997-10-24 1999-07-27 Pharma Nord Uk Ltd 肝臓疾患のための医薬処方
WO2000057871A2 (fr) * 1999-03-30 2000-10-05 Purdue Research Foundation Procedes d'identification d'agents inhibant des facteurs seriques du vieillissement, utilisations et compositions associees
JP2003119127A (ja) * 2001-10-10 2003-04-23 Kanegafuchi Chem Ind Co Ltd 安定な還元型補酵素ｑ製剤
WO2005051370A1 (fr) * 2003-11-28 2005-06-09 Kaneka Corporation Composition a effet protecteur des fonctions hepatiques

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6118719A (ja) * 1984-07-06 1986-01-27 Kao Corp 胆石症治療剤
JPH02233611A (ja) * 1989-01-18 1990-09-17 Merck & Co Inc ＨＭＧ―ＣｏＡレダクターゼ阻害剤と併用される補酵素Ｑ↓１↓０
JPH09187229A (ja) * 1996-01-10 1997-07-22 Idemitsu Material Kk 家禽用飼料組成物
JPH10109933A (ja) * 1996-08-16 1998-04-28 Kanegafuchi Chem Ind Co Ltd 医薬組成物
JPH11199477A (ja) * 1997-10-24 1999-07-27 Pharma Nord Uk Ltd 肝臓疾患のための医薬処方
WO2000057871A2 (fr) * 1999-03-30 2000-10-05 Purdue Research Foundation Procedes d'identification d'agents inhibant des facteurs seriques du vieillissement, utilisations et compositions associees
JP2003119127A (ja) * 2001-10-10 2003-04-23 Kanegafuchi Chem Ind Co Ltd 安定な還元型補酵素ｑ製剤
WO2005051370A1 (fr) * 2003-11-28 2005-06-09 Kaneka Corporation Composition a effet protecteur des fonctions hepatiques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TAKAHASHI T. ET AL.: "Cellular antioxidant defense by a ubiquinol-regenerating system coupled with cytosolic NADPH-dependent ubiquinone reducetase: protective effect against carbon tetrachloride-induced hepatoxocity in the rat", BIOLOGICAL & PHARMACEUTICAL BULLETIN, vol. 19, no. 8, 1996, pages 1005 - 1012, XP002998133 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007034852A1 (fr) * 2005-09-22 2007-03-29 Kaneka Corporation Composition destinée à prolonger la vie et procédé destiné à prolonger la vie
JPWO2007034852A1 (ja) * 2005-09-22 2009-03-26 株式会社カネカ 延命用組成物及び寿命を延長する方法
WO2008069276A1 (fr) 2006-12-06 2008-06-12 Kaneka Corporation Agent thérapeutique contre le cancer et agent anti-carcinogène
EP2123266A1 (fr) * 2006-12-06 2009-11-25 Kaneka Corporation Agent thérapeutique contre le cancer et agent anti-carcinogène
EP2123266A4 (fr) * 2006-12-06 2010-01-06 Kaneka Corp Agent thérapeutique contre le cancer et agent anti-carcinogène

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TW200722077A (en) 2007-06-16

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