WO1994007482A1 - Agent prophylactique et remede contre l'oedeme cerebral - Google Patents

Agent prophylactique et remede contre l'oedeme cerebral Download PDF

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Publication number
WO1994007482A1
WO1994007482A1 PCT/JP1993/001372 JP9301372W WO9407482A1 WO 1994007482 A1 WO1994007482 A1 WO 1994007482A1 JP 9301372 W JP9301372 W JP 9301372W WO 9407482 A1 WO9407482 A1 WO 9407482A1
Authority
WO
WIPO (PCT)
Prior art keywords
cerebral edema
nna
cerebral
mca
prophylactic
Prior art date
Application number
PCT/JP1993/001372
Other languages
English (en)
Japanese (ja)
Inventor
Toshiaki Nagafuji
Toru Matsui
Original Assignee
Chugai Seiyaku Kabushiki Kaisha
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 Chugai Seiyaku Kabushiki Kaisha filed Critical Chugai Seiyaku Kabushiki Kaisha
Publication of WO1994007482A1 publication Critical patent/WO1994007482A1/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
    • A61K31/185—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

Definitions

  • the present invention relates to a prophylactic or therapeutic agent for ischemic cerebral edema, which comprises ⁇ "-nitro-L-arginine (P, abbreviated as L-NNA) or a salt thereof as an active ingredient.
  • a prophylactic or therapeutic agent for ischemic cerebral edema which comprises ⁇ "-nitro-L-arginine (P, abbreviated as L-NNA) or a salt thereof as an active ingredient.
  • nitric oxide is involved in vascular relaxation, platelet aggregation, adhesion suppression, and maintenance of biological functions as an intercellular messenger ( Trends Pharmacol. 10, 428-431, 1989; Trends
  • L-NNA known as an inhibitor of NO synthase (hereinafter abbreviated as NOS)
  • NOS NO synthase
  • Cerebral edema is a condition defined as an increase in brain water volume resulting in an increase in brain volume (see J. Neuropath. Exp. Neurol. 26, III-.14 1967).
  • the pathology that causes cerebral edema can vary. The consequences are death from brain incarceration. It is known that ischemic cerebral edema occurs experimentally and clinically, very early before the appearance of infarct lesions (see Handbook of Stroke Experiments 1990).
  • L-NNA has a preventive or therapeutic effect on ischemic serum cerebral edema, leading to the present invention.
  • the L-NNA used in the present invention is a known substance and can be easily obtained.However, for example, L-NNA can also be obtained by laying down by the method described in J. Am. Cem. So 78.238 (1956). it can.
  • the salt of L-NNA is not particularly limited as long as it is a pharmaceutically acceptable salt.
  • the L-NNA or a salt thereof according to the present invention is prepared by adding suitable excipients, auxiliaries, lubricants, preservatives, stabilizers, wetting agents, emulsifiers, coloring agents, flavoring agents, fragrances, etc. Orally or parenterally, preferably in the form of tablets, granules, fine granules, powders, capsules, syrups, elixirs, drops, solutions, suspensions, emulsions, etc. It can be administered in the form of intravenous administration.
  • the carrier for the formulation may be, for example, lactose, sucrose, sorbitol, mannite, starch such as potato starch or corn starch, a starch derivative, a cellulose derivative or gelatin.
  • Suitable auxiliaries which can be usually used are suitable, and at the same time, lubricants such as magnesium stearate, carbowax or polyethylene glycol can be added. It can be made into capsules and the like.
  • an injection in the case of aqueous preparations, for example, an effective amount of the main component is dissolved in distilled water for injection, and if necessary, isooxidants, stabilizers, and local anesthetics After adding a preservative and the like, and completely dissolving, an injection can be prepared by filtration, filling, sealing, and steam sterilization by a conventional method.
  • an aqueous solution containing the main component dissolved in distilled water for injection may be lyophilized by a conventional method.
  • saccharides such as mannitol, inositol, lactose, maltose, and sucrose, sugar alcohols, glycine, and the like can be added, and lyophilized as usual.
  • the dose of L-NNA or a salt thereof of the present invention can be appropriately selected depending on the patient's body type, age, physical condition, degree of disease, and the like, but is preferably 5 to 100 mg / body per day. is there.
  • the L--NNA or a salt thereof according to the present invention has a therapeutic effect on cerebral edema formed 2-3 times after the onset of ischemic cerebrovascular disease. Pre-administration prior to the onset of cerebral edema can also be expected to have a protective effect on brain adenoma.
  • a control solvent physiological saline 1 ml / kg
  • L-NNA Sigma, 1 mg / kg
  • the water content in the left cerebral hemisphere was measured by the dry weight method. That is, rats were decapitated and sacrificed 48 hours after MCA closure, and the wet weight (W) of the left cerebral hemisphere taken out within 90 seconds was measured. Then, it was dried in an oven at 105 ° C for 5 days, and the dry weight (D) was measured. The water content was obtained from the calculation formula of [(W—D) ZW] ⁇ 100%. Next, using the dried tissue, the sodium and potassium contents were quantified using an atomic absorption spectrophotometer. That is, a certain amount of concentrated nitric acid was added to the dried brain tissue, and the mixture was incubated at 45 ° C for 90 minutes.
  • Number is the number of specimens, Number is the average number of specimens S. E. M
  • Magnesium stearate 0.5 mg l O OmgZl tablets were added and mixed well, and the mixture was directly tabletted with a tableting machine to a diameter of 7 mm and a weight of 10 Omg to obtain tablets.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Agent prophylactique ou remède contre l'÷dème cérébral ischémique, contenant de la Nφ-nitro-L-arginine ou bien un sel de celle-ci comme ingrédient actif.
PCT/JP1993/001372 1992-09-25 1993-09-27 Agent prophylactique et remede contre l'oedeme cerebral WO1994007482A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP29759192 1992-09-25
JP4/297591 1992-09-25

Publications (1)

Publication Number Publication Date
WO1994007482A1 true WO1994007482A1 (fr) 1994-04-14

Family

ID=17848542

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1993/001372 WO1994007482A1 (fr) 1992-09-25 1993-09-27 Agent prophylactique et remede contre l'oedeme cerebral

Country Status (1)

Country Link
WO (1) WO1994007482A1 (fr)

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 113, No. 15, Abstract No. 129875v. *
EUR. J. PHARM., 204, p. 339-340, (1991). *

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