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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
• • 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
  • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
  • A61K31/425—Thiazoles
• • 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
  • A61P9/12—Antihypertensives

Definitions

• This invention provides a new composition of antihypertensive agents o
• N-methylol-peptiylamino acid inhibits angiotensin I-converting enzyme, so it is clear that it is a therapeutic agent for renal hypertension. Has been 0
• venus benide has a uric acid excretion effect and is used as a therapeutic drug for gout, and the compound also secretes and excretes certain organic acids from the renal tubule. It is also known to suppress Until now, the prolonged action of drugs has been attempted using the inhibitory action of probenecid on secretion, and in particular, the combination of penicillin with O is famous.
• diuretics are used in combination for the treatment of hypertension, but there have been reports of the use of probeneid in combination with a diabetic tensin I-converting enzyme inhibitor o
• the present inventors have studied the combined effect of buguchibeneside on N-mercaptosylamino acid, which exhibits an antihypertensive effect by inhibiting angiotensin I converting enzyme.
• the inhibitory activity of angiotensin I-converting enzyme was determined to be N-melkabut A lower dose was observed with probenecid than with Junjun alone, and the reading time could be prolonged o
• the present invention relates to a blood pressure lowering agent characterized by containing N-mercaptosylamino acid and probenecid, and comprises N-mercaptoacetic acid.
• Minic acid refers to those represented by the following formula and includes salts commonly used as such medicaments.
• R 1 represents a hydrogen atom or a lower alkyl group.
• O R 2 represents a hydrogen atom, a lower alkyl group, a phenol group, an arylalkyl group, or an imidazo group. Indicates whether the group is a real alkyl group or an arylalkyl group. Each group is a lower alkyl group, a hydridyl group, or a dihydryl group.
• R 1 and R 2 may together form a pyrrolidine ring, a piperidin ring or a thiazolidine ring; ⁇ is substituted with any of a lower alkyl group, a methyl group, a phenyl group, a phenyl group, a phenyl group, a phenyl group, a pyridyl group and a naphthyl group.
• each of the groups may be a lower alkyl group, a lower hydroxy alkyl group, a lower alkyl group, a hydroxy group, a hydroxy group, or a lower alkoxy group.
• 'No It may be substituted with a group, a halogen atom, a nitro group, an amino group, a lower alkyl-substituted amino group, or an acylamino group.
• Z is shown Chokukusarima other a branch al key record emission having 1 to 3 carbon atoms, R 3 is was or hydrogen atoms indicates the main switch le group, R 4 is a hydrogen atom, ⁇ It represents a sil group or a group obtained by removing R 4 from the formula.
• N-melkabutacil is a compound that has an inhibitory effect on angiotensin I-converting enzyme, and increases blood pressure caused by angiotensin I. O Inhibiting the action o Therefore, the combined effect of buguchibeneside on N-mercaptoacylaminoic acid is based on the effect of angiotensin I on increasing blood pressure. O Implemented in the following manner o
• N-mercaptoacylaminoic acid was administered at a dose of 0.5 i (1 ⁇ ⁇ ) per body weight of 100 ⁇ ⁇ , and angiotensin was administered. Increased by intravenous administration of O Pressure response was measured over time.
• O Angiotensin I converting enzyme inhibitory activity was angiotensin I pressurization inhibition rate (expressed as o
• N is the (2,4) -1-2- (2 -hydroxyfile) which is N-mercapto-asyl amic acid-3-(3- 1-thiazolidin carboxylate (hereinafter referred to as Compound A) suppresses the angiotensin I pressor response by oral administration of 1Z
• This effect of compound A was enhanced in both strength and duration by the combined use of mosquito and probenecid.
• O The combined effect of this probenecid was within the range tested (1 to: L No.) The dependence on the use of probenecid was higher, and the greater the combined use, the greater the potentiating effect.
• Fig. 1 is a graph showing the change in the antihypertensive effect of N-melkabutate syllaminoic acid and probenecid administration. O In the figure, 1 indicates only compound A. In the case of, 2 is a combination of compound A1 and probenecid, 3 is a compound A1 ⁇ and bupeneside 10, and 4 is a combination of compound A1 ⁇ and probenecid. 100, indicating the case of combined use o The suppression rate on the vertical axis is the rate of suppression of pressor response by angiotensin I o
• N — Melobutyryl Mino acid and probenecid should be in the ratio of about 0.1 to 100 Z for the former, about 1 to 100 Z for the former. Therefore, both formulations are stable.
• the present invention provides a hypotensive composition useful as a medicament.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Cardiology (AREA)
• Heart & Thoracic Surgery (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)
• Thiazole And Isothizaole Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

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• 1980
  • 1980-09-20 JP JP55131348A patent/JPS5756425A/ja active Granted
• 1981
  • 1981-09-18 DE DE3152363T patent/DE3152363C2/de not_active Expired
  • 1981-09-18 GB GB8214130A patent/GB2100127B/en not_active Expired
  • 1981-09-18 BE BE2/59361A patent/BE890398A/fr not_active IP Right Cessation
  • 1981-09-18 WO PCT/JP1981/000236 patent/WO1982000954A1/ja not_active Ceased
  • 1981-09-18 IT IT24047/81A patent/IT1139452B/it active
  • 1981-09-18 US US06/380,664 patent/US4424228A/en not_active Expired - Fee Related
  • 1981-09-21 FR FR8117809A patent/FR2490490A1/fr active Granted
• 1982
  • 1982-05-14 SE SE8203054A patent/SE8203054L/ not_active Application Discontinuation

Patent Citations (1)

Non-Patent Citations (1)

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