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WO1992013544A1 - Agent de prevention et de traitement de la myocardite virale - Google Patents

Agent de prevention et de traitement de la myocardite virale Download PDF

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Publication number
WO1992013544A1
WO1992013544A1 PCT/JP1992/000069 JP9200069W WO9213544A1 WO 1992013544 A1 WO1992013544 A1 WO 1992013544A1 JP 9200069 W JP9200069 W JP 9200069W WO 9213544 A1 WO9213544 A1 WO 9213544A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
myocarditis
viral myocarditis
virus
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP1992/000069
Other languages
English (en)
Japanese (ja)
Inventor
Akira Matsumori
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fujisawa Pharmaceutical Co Ltd
Original Assignee
Fujisawa Pharmaceutical 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 Fujisawa Pharmaceutical Co Ltd filed Critical Fujisawa Pharmaceutical Co Ltd
Publication of WO1992013544A1 publication Critical patent/WO1992013544A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides

Definitions

  • This invention is based on the formula
  • the present invention relates to a prophylactic / therapeutic agent for viral myocarditis comprising as an active ingredient the compound shown in 3 or a pharmaceutically acceptable salt thereof.
  • Viral myocarditis is a disease that, when severe, can lead to heart failure and even death.
  • various antiviral and immunopotentiating agents have been tried to determine whether they are effective against viral myocarditis, but at present, effective drugs are known. It's a lazy lady.
  • the second inventor has been known as a drug for viral infectious disease as a result of an independent study in a situation in which the emergence of an effective drug for viral myocarditis is desired.
  • a compound represented by the following formula (I) is expected to be a predictor of viral myocarditis. We have obtained new knowledge that it is effective as a preventive and therapeutic agent, and as a result of further research, we have completed this process.
  • the agent for preventing or treating viral myocarditis according to the present invention comprises, as an active ingredient, a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof.
  • the agent for preventing and treating viral myocarditis according to the present invention can be used for preventing and treating various types of viral myocarditis in humans and animals.
  • Pharmaceutically acceptable salts of compound (I) used as an active ingredient in the present invention include, for example, sodium salt, potassium salt, calcium salt and the like.
  • Organic or inorganic salts such as salt, ammonia salt, ethanolamine salt, triethylamine salt, dicyclohexylamine salt, etc. , Lactate, trifluoroacetate, lactate, maleate, fumarate, tartrate, citrate, methansulfonate, hydrochloride , Sulfate, nitrate, phosphate And acid addition salts with organic acids or inorganic acids.
  • Compound (I) contains one or more stereoisomers depending on the asymmetric carbon atom in the molecule, and all of these compounds can be used as the active ingredient of the present invention. Wear .
  • the compound (I) used as an active ingredient in the present invention and a pharmaceutically acceptable salt thereof reduce myocardial damage in acute myocarditis and have a remarkable survival rate. Improvement was observed, and viral myocarditis C is a typical virus caused by myocarditis, for example, coxsackie virus, ecovirus, etc. Enterovirus)) as a preventive and therapeutic agent.
  • Test Example 1 Anti-encephalomyocarditis virus activity by compound A-administered mouse peritoneal cells and mast cells
  • mice BalbZc, male, 5 weeks old, 10 mice per group (30 mice in phosphate-administered saline administration group)
  • Compound A administration 1, 0.01 mg / kg, once a day for 3 days intraperitoneally
  • Peritoneal cells Collected by centrifugation from the peritoneal lavage fluid of HBSS (3 ml) of the exsanguinated mouse
  • Splenocytes The spleen of the exsanguinated mouse was washed with a glass homogenizer, filtered with a metal mesh, lysed with 0.85% NH 4 C1, washed with HBSS, and used for experiments. .
  • Experimental system A single eyebrow of BalbZc 3T3 cells (MEM medium containing 10% fetal serum) was infected with encephalomyocarditis (EMC) virus for 1 hour with HOI 1 and then peritoneal cells or Splenocytes were added, and the cells were cultured for 16 hours in a MEM medium containing 0.5% ⁇ fetal serum.
  • EMC encephalomyocarditis
  • Rhinovirus 5 Virus fi i ⁇ f direct effector-cell EZI ratio (pfxi / ml) Mean ⁇ SD (log)
  • EZ I ratio Effector Target cell ratio Mouse peritoneal cavity with PBS-PEC phosphate buffered saline cell
  • Test Example 2 Anti-coccalus B3 virus activity by mouse peritoneal cells and splenocytes administered with Compound A
  • mice C3HZ He strain, male, 8 weeks old, 10 mice per group (30 mice in phosphate-administered saline administration group)
  • Compound A administration 1, 0.01 mg / kg, intraperitoneally once a day for 3 days
  • Peritoneal cells Collected by centrifugation from the peritoneal lavage fluid of HBSS (3 ml) of the exsanguinated mouse
  • Spleen cells Depleted The spleen of the mouse was crushed with a glass homogenizer, filtered with a metal mesh, lysed with 0.85% NH 4 C1, washed with HBSS, and used for experiments. Using. Experimental system C3HZ He-mass fetal fibroblasts (MEM medium containing 10% fetal serum :) After infecting B3 virus with MOI 1 for 1 hour, peritoneal cells or spleen cells were added, and the cells were cultured for 16 hours in a MEM medium containing 0.5% fetal fetus serum. After freeze-thawing was repeated twice to destroy the cells, the amount of virus in the supernatant was measured by the plaque method using FL cells.
  • PE PBS-SC, 0.1 Olmg / kg-SC and 1 mgZ kg-SC have the same meanings as in Test Example 1.
  • mice Four week old Balb / c mice were intraperitoneally inoculated with 100 plaquef orming units (pfu;) of encephalomyocarditis C EMC;) virus.
  • Compound A was discontinued after daily administration for 4 days.
  • the prophylactic and therapeutic agents for viral myocarditis of the present invention are, for example, the active substances of the present invention.
  • a solid, semi-solid, or liquid formulation containing the compound in an organic or inorganic carrier or excipient suitable for parenteral or parenteral administration be able to .
  • the active ingredient may be, for example, a tablet, pellet, capsule, suppository, suppository, solution, emulsion, suspension, and usually a non-toxic pharmaceutically acceptable carrier. It is used by mixing to form an appropriate dosage form.
  • the carriers include water, glucose, lactose, arabia gum, gelatin, mannitol, starch paste, and magnesium paste.
  • the preventive or therapeutic agent for myocardial myocarditis may also contain a preservative or a bacteriostat to stably maintain the activity of the impeached component in the desired preparation.
  • the amount of the active ingredient contained in the agent for preventing or treating viral myocarditis is an amount sufficient to exert the desired therapeutic effect on the prophylaxis or disease process and condition. .
  • this prophylactic / therapeutic agent for viral myocarditis is applied to humans, it is desirable to administer it by a method such as intravenous injection, subcutaneous injection, intramuscular injection or oral administration.
  • the dose of the active ingredient, compound (I) or a pharmaceutically acceptable salt of the present invention varies depending on the conditions such as the age of each individual patient to be treated and the degree of illness. However, humans generally receive a daily dose of about 0.01 to 10 mg of active ingredient for prophylactic or therapeutic purposes.
  • Example 2 The above is formulated in a conventional manner to give tablets.
  • Example 2 The above is formulated in a conventional manner to give tablets.
  • the above is formulated in a conventional manner to make a capsule.
  • the vial is aseptically dispensed to contain the compound AlOOmg and sealed to remove water and bacterium. Before use, add 2 ml of 0,5% lidocaine injection to make an injection.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Agent de prévention et de traitement de la myocardite virale présentant une efficacité excellente, ledit agent contient, à titre d'ingrédient actif, un composé représenté par la formule (3) ou un sel pharmaceutiquement acceptable dudit composé.
PCT/JP1992/000069 1991-01-30 1992-01-28 Agent de prevention et de traitement de la myocardite virale Ceased WO1992013544A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP9834691 1991-01-30
JP3/98346 1991-01-30
JP25408991 1991-06-27
JP3/254089 1991-06-27

Publications (1)

Publication Number Publication Date
WO1992013544A1 true WO1992013544A1 (fr) 1992-08-20

Family

ID=26439535

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1992/000069 Ceased WO1992013544A1 (fr) 1991-01-30 1992-01-28 Agent de prevention et de traitement de la myocardite virale

Country Status (1)

Country Link
WO (1) WO1992013544A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0488041A3 (en) * 1990-11-26 1993-04-14 Fujisawa Pharmaceutical Co., Ltd. A pharmaceutical composition for cytomegalovirus infection
CN104258297A (zh) * 2014-10-15 2015-01-07 鲁翠花 一种治疗气滞血瘀型病毒性心肌炎的中药及其制备方法
CN111514237A (zh) * 2020-05-29 2020-08-11 中国人民解放军陆军第八十二集团军医院 一种治疗病毒性心肌炎的中药组合物及其制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60104019A (ja) * 1983-11-10 1985-06-08 Fujisawa Pharmaceut Co Ltd ウイルス感染症用薬剤
JPH02288894A (ja) * 1979-10-11 1990-11-28 Fujisawa Pharmaceut Co Ltd 新規なペプタイド、その医薬として許容される塩、およびその製造法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02288894A (ja) * 1979-10-11 1990-11-28 Fujisawa Pharmaceut Co Ltd 新規なペプタイド、その医薬として許容される塩、およびその製造法
JPS60104019A (ja) * 1983-11-10 1985-06-08 Fujisawa Pharmaceut Co Ltd ウイルス感染症用薬剤

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0488041A3 (en) * 1990-11-26 1993-04-14 Fujisawa Pharmaceutical Co., Ltd. A pharmaceutical composition for cytomegalovirus infection
CN104258297A (zh) * 2014-10-15 2015-01-07 鲁翠花 一种治疗气滞血瘀型病毒性心肌炎的中药及其制备方法
CN111514237A (zh) * 2020-05-29 2020-08-11 中国人民解放军陆军第八十二集团军医院 一种治疗病毒性心肌炎的中药组合物及其制备方法

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