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WO1997036594A1 - Medicaments contenant des vitamines b¿2? - Google Patents

Medicaments contenant des vitamines b¿2? Download PDF

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Publication number
WO1997036594A1
WO1997036594A1 PCT/JP1997/001079 JP9701079W WO9736594A1 WO 1997036594 A1 WO1997036594 A1 WO 1997036594A1 JP 9701079 W JP9701079 W JP 9701079W WO 9736594 A1 WO9736594 A1 WO 9736594A1
Authority
WO
WIPO (PCT)
Prior art keywords
toxin
emissions
vita
preventive
endotoxin
Prior art date
Application number
PCT/JP1997/001079
Other languages
English (en)
Japanese (ja)
Inventor
Seiichi Araki
Mamoru Suzuki
Naoaki Watanabe
Original Assignee
Eisai Co., Ltd.
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 Eisai Co., Ltd. filed Critical Eisai Co., Ltd.
Publication of WO1997036594A1 publication Critical patent/WO1997036594A1/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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the present invention relates to a butoxy Nshi ® click prophylactic treatment agent containing Vita Mi emissions B 2. More particularly, the present invention relates to Tokishinshi ® click preventive therapeutic agent derived from bacteria containing the Vita Mi emissions B 2. Background art
  • Vita Mi emissions B 2 is an alias for re Bofura bottle and its derivatives are substances naturally contained many liver, brewer's yeast, milk, meat, eggs, green vegetables. It is used as a drug for the prevention and treatment of diseases such as stomatitis, cheilitis, glossitis, acute and chronic eczema, seborrheic eczema and pellagra.
  • Bi evening Mi emissions B 2 is bound i.e. in vivo, in the form of a hula Binmono j click Reochi de (FN).
  • Flavin adenine dinucleotide click Reochi de called off La bottle proteins or flavin enzyme It functions as a prosthetic group for oxidoreductase, and plays a central role in the oxidative degradation of sugars, lipids, and amino acids, and in electron transport in mitochondrial microsomes.
  • FAD Flavin adenine dinucleotide click Reochi de
  • Toxins are substances that are toxic to humans and have antigenicity. Based on their origin, they are classified into animal-derived toxins, plant-derived toxins, and bacterial-derived toxins (endotoxin, endotoxin).
  • the bacterial antigen of enteric bacteria ie, the 0 antigen (0-specific polysaccharide antigen)
  • endotoxin endotoxin
  • endotoxin endotoxin
  • endotoxin endotoxin
  • It is a complex of polysaccharide, lipid, and protein.
  • end toxin Shock refers to a state of shock caused by infection with Gram-negative bacilli that produce endotoxins, such as Escherichia coli, modified bacteria, and Pseudomonas aeruginosa. Then, as the disease progresses, it shifts to a low circulation state,
  • D 1 C Disseminated Intravascular Coagulatation Disseminated Intravascular Coagulation Syndrome
  • enteroxin Bacterial exotoxin (exotoxin) is a high-molecular-weight protein that is thermally unstable and extremely toxic.
  • Treatment of endotoxin shock involves first surgical removal of the source of infection and then administering antibiotics susceptible to the infectious organism or antibiotics with a broad spectrum of antibiotics.
  • compounds having an anti-endotoxin activity have been actively developed.
  • Japanese Patent Application Laid-Open Nos. 60-158172 and 61-293394 are disclosed. It is disclosed in the official gazette, Japanese Patent Application Laid-Open No. Sho 60-243, and Japanese Patent Application Laid-Open No. Hei 2-131467.
  • the present invention is a Tokishinshi ® click prophylactic treatment agent containing Vita Mi emissions B 2. More particularly a Tokishinshi ® click preventive therapeutic agent derived from bacteria containing the Vita Mi emissions B 2. BEST MODE FOR CARRYING OUT THE INVENTION
  • the take Vita Mi emissions B 2 in the present invention a Li Bofura bottle, Li Nsanri Bofura Bin'na Application Benefits um, Fra Binmono nucleocapsid click Reochi de (FMN) or flavin Ade two Njinu click Reochi de (PAD).
  • the dose of Vita Mi emissions B 2 in the present invention 1 kg body weight per a l OOmg from 0. lmg, is favored by rather a 50mg from 0. 5 m, more and preferable rather is 25mg from lmg.
  • the method of administration Vita Mi emissions B 2 is not particularly limited, in the case of severe tio click state lay preferred to administered as injections, if lighter symptoms administered orally or rectally it can.
  • Vita Mi emissions B 2 are not known overload disorder by administration, a high-bi evening Mi down very secure.
  • the vitamin according to the present invention can be made into injections, tablets, granules, powders, capsules and the like by conventional techniques.
  • a solubilizing agent such as nicotinyl Nsan'a mi de, It is necessary to make an injection using a synthetic surfactant or lecithin.
  • Tokishinsho click prophylactic treatment agent containing a bi evening Mi emissions B 2 causes excessive death in the body such as leukin 1, interleukin 6, and tumor necrosis factor (TNF), leading to shock death.
  • TNF tumor necrosis factor
  • Figure I is a graph showing changes in mean aortic pressure by bi evening Mi emissions B 2 administration.
  • Figure 2 is Ru graph view showing a change in cardiac output by Vita Mi emissions B 2 administration.
  • FIG. 3 is a graph showing changes in the heart rate by Vita Mi emissions B 2 administration
  • FIG. 4 is a graph showing changes in the mean pulmonary artery pressure by Vita Mi emissions B 2 administration.
  • SLC ICR male mice were used as animals.
  • lipopolysaccharide derived from Escherichia coli Escherichia coli serotype 0127-B8 (manufactured by Sigma, hereinafter referred to as LPS) is used and dissolved in physiological saline for injection. Used.
  • LPS lipopolysaccharide derived from Escherichia coli Escherichia coli serotype 0127-B8
  • Vita Mi emissions B 2 Li Nsanri Bofu La Bin'na preparative with Li um, it was dissolved in distilled water for injection, sterile filtered by full I Luther 0. 22 ra 5 w / v % Of the injection solution (hereinafter referred to as the present sample). Distilled water for injection was used as a control sample.
  • mice were inoculated with 50 mg / kg of endotoxin intravenously 24 hours before, simultaneously with, and after administration of this sample or control sample. Then, the survival rate 4 days after the administration was measured. The effects were statistically compared by two tests. The results are shown in Tables 1 and 2.
  • a general anesthesia was performed with an at-sulfate pin (0.05 mg / kg, i.m.) and bentobarbital Na (25 mg / kg, i.v.), and bankronium bromide (0.2 mg / kg, i.m. kg, i.v.), the experiment was performed under controlled respiration.
  • beagle dogs (15 dogs) were divided into three groups according to drug dose.
  • the value before endotoxin administration was measured when the circulating artery was stabilized, and the endotoxin was subsequently reduced to 0.1 Irag.
  • An endotoxin shock model was created by instilling drip at a rate of / kg / hr for 6 hours.
  • Treatment group I (5 animals), the Vita Mi emissions B 2 5 mg / kg was administered intravenously to endotoxin administration immediately before and after the start 1 8 0 min.
  • Treatment group II (5 animals), endotoxin administration after 2 4 hours before last and bicycloalkyl evening to 1 8 0 minute after the start of Mi emissions B 2 20 mg / kg was administered intravenously.
  • the control group (5 animals) received the same amount of saline (control). The measurement was performed until 360 minutes after the start of the endotoxin administration.
  • FIGS. 1 to 4 show the results. These FIGS. 1 to 4 Vita Mi emissions B 2 20 mg / kg administered, end-preparative Kishinsho click upon hemodynamics example mean aortic pressure, to improve such a significant cardiac output was observed, end- It has been shown to be effective as a preventive and remedy for toxic shock.
  • Example 3
  • mice ICR male mice (5-6 weeks old, weighing 28-32 g) were purchased from Japan SLC, Inc. and used after acclimation. Using group 1 0 mice Mice re Nsanri Bofura Bin'na Application Benefits um dissolved in saline (B 2 Na) at a ratio of 2 0 mg / k, yellow staphylococci-derived Entero toxin (SEB) 24 hours before, 3 hours after, and 3 hours after vaccination. On the other hand, as a control group, the same volume of physiological saline was administered. SEB (30 g / mouse) was mixed with D-galactosamine (40 mg / mouse) and inoculated intraperitoneally. The protective effect of B 2 Na against toxin shock was determined by measuring the survival rate 4 days after inoculation. Table 3 shows the results. Table 3
  • the present invention is a preventive and therapeutic agent for toxin shock, and is also effective as a preventive and therapeutic agent for DIC induced by toxin shock.
  • D1C is also called disseminated intravascular blood coagulation or pervasive blood coagulation, and is used for the release of tissue thromboplastin into the blood and vascular endothelial disorders due to underlying diseases such as infectious diseases. Activates the coagulation system as a trigger, causing multiple systemic microthrombi and organ damage, as well as enhancing fibrinolytic system activation and causing a prominent bleeding tendency. . I am sick.
  • the prophylactic / therapeutic agent of the present invention is effective not only for endotoxin shock caused by gram-negative bacteria but also for endotoxin shock caused by gram-positive bacteria.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Toxicology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

Cette invention concerne des agents de prévention ou des médicaments qui permettent de lutter contre les chocs causés par des toxines, et qui contiennent de la vitamine B2. Cette vitamine B2 consiste en de la riboflavine, du phosphate de riboflavine de sodium, un mononucléotide de flavine et/ou un dinucléotide d'adénine de flavine.
PCT/JP1997/001079 1996-04-01 1997-03-28 Medicaments contenant des vitamines b¿2? WO1997036594A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP8/78698 1996-04-01
JP7869896 1996-04-01
JP09135297A JP3286831B2 (ja) 1996-04-01 1997-03-27 ビタミンｂ２含有医薬
JP9/91352 1997-03-27

Publications (1)

Publication Number Publication Date
WO1997036594A1 true WO1997036594A1 (fr) 1997-10-09

Family

ID=26419752

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1997/001079 WO1997036594A1 (fr) 1996-04-01 1997-03-28 Medicaments contenant des vitamines b¿2?

Country Status (2)

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JP (1) JP3286831B2 (fr)
WO (1) WO1997036594A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002074313A1 (fr) * 2001-03-21 2002-09-26 Eisai Co., Ltd. Médicaments à base de vitamine b2 réduite
WO2003075935A1 (fr) * 2002-03-11 2003-09-18 Eisai Co., Ltd. Medicaments contenant des composes du type riboflavine

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090054443A1 (en) 2006-03-15 2009-02-26 Suntory Limited Compositions containing riboflavin and sesamin-class compounds
KR101525264B1 (ko) 2007-03-15 2015-06-02 산토리 홀딩스 가부시키가이샤 항피로제
JP6129395B1 (ja) * 2016-10-29 2017-05-17 誠一 荒木 ミトコンドリア活性化に起因した血管内皮細胞保護回復用還元型ビタミンｂ２製剤
JP2018070581A (ja) * 2017-04-19 2018-05-10 誠一 荒木 還元型ビタミンｂ２製剤

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH01146819A (ja) * 1987-10-26 1989-06-08 Sandoz Ag 有機化合物の改良または関連改良
JPH05201864A (ja) * 1991-09-13 1993-08-10 Eisai Co Ltd 免疫賦活・感染防御剤及びその製造方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH01146819A (ja) * 1987-10-26 1989-06-08 Sandoz Ag 有機化合物の改良または関連改良
JPH05201864A (ja) * 1991-09-13 1993-08-10 Eisai Co Ltd 免疫賦活・感染防御剤及びその製造方法

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002074313A1 (fr) * 2001-03-21 2002-09-26 Eisai Co., Ltd. Médicaments à base de vitamine b2 réduite
US7579325B2 (en) 2001-03-21 2009-08-25 Eisai R & D Management Co., Ltd. Drugs containing reduced of vitamin B2
WO2003075935A1 (fr) * 2002-03-11 2003-09-18 Eisai Co., Ltd. Medicaments contenant des composes du type riboflavine
EP1484061A4 (fr) * 2002-03-11 2009-12-23 Eisai R&D Man Co Ltd Medicaments contenant des composes du type riboflavine

Also Published As

Publication number Publication date
JP3286831B2 (ja) 2002-05-27
JPH1029941A (ja) 1998-02-03

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