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WO2008032814A1 - Agent pharmaceutique contenant de l'aspirine - Google Patents

Agent pharmaceutique contenant de l'aspirine Download PDF

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Publication number
WO2008032814A1
WO2008032814A1 PCT/JP2007/067910 JP2007067910W WO2008032814A1 WO 2008032814 A1 WO2008032814 A1 WO 2008032814A1 JP 2007067910 W JP2007067910 W JP 2007067910W WO 2008032814 A1 WO2008032814 A1 WO 2008032814A1
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WO
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Prior art keywords
group
thrombus
formation
aspirin
embolus
Prior art date
Application number
PCT/JP2007/067910
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English (en)
Japanese (ja)
Inventor
Mayumi Watanabe
Original Assignee
Mitsubishi Tanabe Pharma 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 Mitsubishi Tanabe Pharma Corporation filed Critical Mitsubishi Tanabe Pharma Corporation
Priority to JP2008534401A priority Critical patent/JPWO2008032814A1/ja
Publication of WO2008032814A1 publication Critical patent/WO2008032814A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a medicament containing aspirin, particularly a medicament for the prevention and / or treatment of a disease associated with the formation of a thrombus or an embolus or a disease caused by the formation of a blood plug or an embolus.
  • Aspirin is widely used as an antipyretic anti-inflammatory analgesic. This is because aspirin acts on the arachidonic acid cascade and inhibits the production of prostaglandins that play an important role in inflammation by inhibiting the activity of cycloxygenase (COX).
  • COX cycloxygenase
  • COX A2 thromboxane A2
  • aspirin is also useful as an antithrombotic drug, and the therapeutic effect of aspirin has already been established in reducing myocardial infarction and ischemic cerebrovascular disease (Patrono, C, N. Engl. J. Med., 330, 1287-1294, 1994).
  • aspirin has a function of inhibiting the production of prostacyclin (PGI2) by inhibiting vascular wall cycloxygenase (COX). Since this PGI2 has a vasodilatory action, contrary to TXA2, a thrombus is formed when the production of PGI2 is suppressed by aspirin. That is, aspirin works both in the direction in which the thrombus is not formed and in the direction in which it is formed. Thus, aspirin has two opposing actions. This action characteristic is called “aspirin dilemma” and is a clinical problem. On the other hand, the use of small amounts of aspirin was suggested as one of the solutions of the aspirin dilemma.
  • R is a hydrogen atom, C-C alkyl group, C-C cycloalkyl group, C-C
  • 1 1 6 3 7 1 represents a halogenated alkyl group, a halogen atom, or a C C aryl group; R represents water
  • n represents an integer of 1 to 4
  • Aminobenzenesulfonic acid derivatives represented by the above formula show excessive accumulation of intracellular calcium ions in myocardium or vascular smooth muscle (Japanese Patent Laid-Open No. 3-7263) and intracellular sodium ions (see Reference Example 1 below). Inhibition, and calcium / protein handling system of sodium / canoresome (Journal of Cardiac Failure Vol.8 No.5 Suppl.2002, S230; see Reference Example 2 below), and sarcoplasmic reticulum calcium ATPase (J. pharmacology and experimental studies. 298, 1161-1166, 2001), and is known to have an action of regulating intracellular calcium concentration or intracellular calcium concentration change rate.
  • the aminoamino sulfonic acid derivative of the above general formula (I) has an action of suppressing excessive accumulation of intracellular calcium ions in the myocardium or vascular smooth muscle. Suppresses or reduces myocardial damage, cardiac stimulation conduction disorder, etc. without having an action, / 3 receptor blocker-like action, or calcium channel antagonist-like action, and ischemic heart disease (eg, myocardial infarction, JP-A-3-7263 and JP-A-4-39127 disclose that it can be a useful preventive or therapeutic agent for angina pectoris), heart failure, hypertension or arrhythmia.
  • ischemic heart disease eg, myocardial infarction, JP-A-3-7263 and JP-A-4-39127 disclose that it can be a useful preventive or therapeutic agent for angina pectoris
  • heart failure e.g, myocardial infarction, JP-A-3-7263 and JP-A-4-39127 disclose that it can be a useful
  • JP-A-10-298077 discloses that the compound has the effect of remarkably improving the decrease in cardiac function in the pathology of cardiomyopathy, as well as the effect of improving the survival rate and prolonging life in the long term in sudden cardiomyopathy.
  • International Publication No. WO99 / 40919 discloses that the compound is a myocardial sarcoplasmic reticulum. It has been disclosed that it has an uptake promoting action and is useful for the treatment or prevention of diastolic disorders. However, to the best of the inventors' knowledge, the ability to use such compounds in combination with aspirin has never been reported!
  • the present invention suppresses the dose of aspirin by combining aspirin with a substance that can be used to prevent and / or treat a disease associated with the formation of a thrombus or embolism when used in combination with aspirin. It aims at providing the medicine which can be. Furthermore, in the formation of a thrombus or embolism characterized by the combined use of aspirin and a substance capable of preventing and / or treating a disease associated with the formation of a thrombus or embolism when used in combination with aspirin. Means for solving the problems aimed at providing a method for the prevention and / or treatment of diseases involved
  • a pharmaceutical comprising a combination of aspirin and the compound described in any of the following (a) to (d):
  • R is a hydrogen atom, a C-C alkyl group, a C-C cycloalkyl group, a C-C
  • 1 1 6 3 7 1 represents a halogenated alkyl group, a halogen atom, or a C C aryl group; R represents water
  • n represents an integer of 1 to 4.
  • the above-mentioned medicament wherein the calcium handling protein is a sodium / force lucium exchange system or a sarcoplasmic reticulum calcium ATPase;
  • aspirin and 5 methyl-2 (piperazine 1 (I) a drug according to item (1) or (2) above, which is a combination of benzenesulfonic acid or a salt thereof, or a hydrate or solvate thereof;
  • a medicine according to the above item (1) or (2) which comprises a combination of (piperazine 1-yl) benzene sulfonic acid monohydrate.
  • any one of the above medicaments for the prevention and / or treatment of a disease associated with the formation of a thrombus or an embolus or a disease caused by the formation of a thrombus or an embolus (6)
  • the medicament according to (5) above, wherein the disease associated with the formation of a thrombus or embolus or the disease caused by the formation of a thrombus or embolus is an ischemic disease; and (7)
  • the pharmaceutical according to the above item (5), wherein the associated disease or the disease caused by the formation of a thrombus or embolus is heart failure, myocardial infarction, cerebral infarction, angina pectoris, or peripheral artery occlusion.
  • R is a hydrogen atom, a C-C alkyl group, a C-C cycloalkyl group, a C-C
  • 1 1 6 3 7 1 represents a halogenated alkyl group, a halogen atom, or a C C aryl group; R represents water
  • n represents an integer of 1 to 4.
  • an aspirin sulfonic acid derivative or salt thereof, or a hydrate or solvate thereof, an aspirin-enhancing agent for inhibiting platelet aggregation (10) 5 methyl 2- (piperazine 1 B) Benzenesulfonic acid or a salt thereof, or an enhancer of platelet aggregation inhibitory action of aspirin containing hydrate or solvate thereof; and (11) 5-methyl-2- (piperazine 1yl) benzenesulfonic acid '
  • a disease associated with the formation of a thrombus or an embolus which comprises using (12) aspirin in combination with a compound according to any one of the following (a) to (d): Methods for preventing and / or treating diseases caused by thrombus or embolism formation:
  • R is a hydrogen atom, a C-C alkyl group, a C-C cycloalkyl group, a C-C
  • 1 1 6 3 7 1 represents a halogenated alkyl group, a halogen atom, or a C C aryl group; R represents water
  • n represents an integer of 1 to 4 To express.
  • the calcium handling protein is a sodium / force lucium exchange system or a sarcoplasmic reticulum calcium ATPase;
  • aspirin and 5 methyl-2 (piperazine 1 (I) benzenesulfonic acid or a salt thereof, or a hydrate or solvate thereof in combination the method according to item (12) or (13) above;
  • aspirin and 5 methyl-2 (piperazine 1 (I) benzenesulfonic acid or a salt thereof, or a hydrate or solvate thereof in combination, the method according to item (12) or (13) above;
  • (15) aspirin and 5 aspirin and 5.
  • R is a hydrogen atom, a C 1 -C alkyl group, a C—C cycloalkyl group, C—C
  • 1 1 6 3 7 1 represents a halogenated alkyl group, a halogen atom, or a C C aryl group; R represents water
  • n represents an integer of 1 to 4.
  • an aspirin for the manufacture of a medicament for the prevention and / or treatment of a disease associated with the formation of a thrombus or an embolus or a disease caused by the formation of a thrombus or an embolus and
  • an aminobenzenesulfonic acid derivative represented by the above general formula (I) or a physiologically acceptable salt thereof, or a combination of hydrates or solvates thereof is provided.
  • a medicament comprising a combination of aspirin and the compound according to any one of (a) to (d).
  • the medicament of the present invention is useful for the prevention and / or treatment of a disease associated with the formation of a thrombus or embolus or a disease caused by the formation of a thrombus or embolus, and the medicament of the present invention uses aspirin for the purpose of inhibiting platelet aggregation. It is useful for the prevention and / or treatment of the diseases used.
  • FIG. 1 shows the platelet coagulation inhibitory effect of aspirin and caldaret monohydrate.
  • FIG. 2 shows the effect of caldaret monohydrate on the antiplatelet aggregation activity of aspirin.
  • the medicament of the present invention contains aspirin (acetyl salicylic acid: CH COOC) as the first active ingredient.
  • the medicament of the present invention contains one of the following forces (a) to (d) as the second active ingredient.
  • the enhancer of the present invention includes one of the above (a) to (d)! /.
  • the second active ingredient (a) of the medicament of the present invention is particularly a compound that acts on a calcium handling protein and has an action of regulating intracellular calcium concentration or intracellular calcium concentration change rate.
  • calcium handling protein is a protein selected from the group consisting of voltage-dependent calcium channel, sodium / calcium exchange system, sodium / proton exchange system, cell membrane calcium ATPase, calcium release channel, and sarcoplasmic reticulum calcium ATPase.
  • the present invention ! / Is preferred! / As sodium / calcium exchange system (Circ Res., 2001, 88, 864-876), and sarcoplasmic reticulum.
  • the second active ingredient (b) of the medicament of the present invention is not particularly limited as long as it is a compound having an action of suppressing the excessive accumulation of intracellular calcium ions. Whether it is a compound that suppresses intracellular calcium ion overaccumulation or not is disclosed in Japanese Patent Laid-Open No. 3-7263 and Reference Example 3 shown below. It can be determined according to the method described above.
  • the second active ingredient (c) of the medicament of the present invention is not particularly limited as long as it is a compound having an action of suppressing the excessive accumulation of intracellular sodium ions. Whether or not the compound suppresses intracellular sodium ion overaccumulation can be determined according to the method described in Reference Example 2 below.
  • the compound represented by the above general formula (I), which is the second active ingredient (d) of the medicament of the present invention, can be mentioned as a substance that enhances the platelet aggregation inhibitory action of aspirin.
  • the compound enhances the platelet aggregation inhibitory action of aspirin, so that the aspirin dose can be kept low by using it together with aspirin.
  • the C C alkyl group defined by R includes, for example, a methyl group, ethyl
  • the C—C cycloalkyl group includes cyclopropyl
  • Examples of the C—C halogenated alkyl group include trifluoromethyl.
  • halogen atom examples include a fluorine atom, a chlorine atom, and a bromine atom.
  • Examples of the 6 12 group include a phenyl group and a naphthyl group.
  • R include a hydrogen atom, a C 1 -C alkyl group, and a C—C cycloalkyl group.
  • a trifluoromethyl group a halogen atom or a phenyl group
  • more preferable examples include an alkyl group, a cyclohexyl group, a trifluoromethyl group, chlorine, wherein R is C C
  • An atom, a bromine atom or a phenyl group can be mentioned, and a methyl group or a propyl group is particularly preferable.
  • Examples of the C C alkyl group defined by R include, for example,
  • Examples include an alkyl group.
  • Examples of the aralkyl group of c-c include a benzyl group and a phenol.
  • the aralkyl group includes a cyano group; a nitro group; a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a tert-butoxy group, a pentyloxy group, an isopentyloxy group, a tert-pentyloxy group.
  • An alkoxy group of CC such as a silyl group or a hexyloxy group; a halogen as defined above for R
  • R include a hydrogen atom; a C 1 -C alkyl group; or a C—C alkyl group.
  • a C 1 -C 3 aralkyl group which may have a group, more preferably, R is water
  • N is preferably 2.
  • a more preferable compound is that R is substituted at the 5-position.
  • particularly preferred examples include 5-methyl-2- (piperazine 1yl) benzenesulfonic acid and 5-n-propyl2 (piperazine 1yl) benzenesulfonic acid.
  • salts of the compounds listed above are also included in the scope of the present invention.
  • any hydrate or solvate of these may be used as the active ingredient of the medicament of the present invention.
  • the aminobenzenesulfonic acid derivative represented by the above general formula (I) is a known compound, for example, Japanese Patent Application Nos. 3-7263 and 9 221479, European Patent Application Publications. It is a compound that can be easily synthesized by methods described in Japanese Patent Publication Nos. 390654 and 779283, US Patent Publication Nos. 5053409 and 5990113, and can be easily obtained by those skilled in the art.
  • the form of the medicament of the present invention is not particularly limited and can take various forms available to those skilled in the art, and can be administered orally or parenterally.
  • Examples of the dosage form for oral administration include granules, fine granules, powders, tablets, hard capsules, soft capsules, syrups, emulsions, suspensions or liquids.
  • Examples of the dosage form for parenteral administration include injections, suppositories, and transdermal agents.
  • the active ingredient is a commonly used pharmaceutical additive such as a solid or liquid pharmaceutical carrier or excipient, stabilizer, lubricant, sweetener, preservative, suspending agent, etc.
  • the content of the therapeutically or prophylactically active ingredient with respect to the carrier ingredient is preferably in the range of 1% by weight to 90% by weight! /.
  • solid components used include lactose, white clay, sucrose, crystalline cellulose, corn starch, talc, agar, pectin, acacia, stearic acid, magnesium stearate, lecithin, sodium chloride and the like.
  • liquid carriers are syrup, glycerin , Peanut oil, polybutylpyrrolidone, olive oil, ethanol, benzyl alcohol, propylene glycol, water and the like.
  • the dose may be appropriately determined for each active ingredient in consideration of the patient's symptoms, weight, age, sex, etc., but the first active ingredient aspirin is 0.01 to 1000 mg / kg body weight, the second active ingredient is 5-methyl-2 (piperazine 1 yl) benzenesulfonic acid 'monohydrate as a representative example, ; 1000 mg / kg body weight can be administered 1 to several times a day.
  • the medicament of the present invention is effective as an antithrombotic drug because it has a platelet aggregation inhibitory action and can prevent thrombus formation. Therefore, the medicament of the present invention is a disease associated with the formation of a thrombus or an embolus or a disease caused by the formation of a thrombus or an embolus, such as an ischemic disease, more specifically heart failure, myocardial infarction, cerebral infarction, angina pectoris, It is effective for the prevention and / or treatment of diseases selected from the group consisting of arteriosclerosis and peripheral arterial occlusion.
  • an ischemic disease more specifically heart failure, myocardial infarction, cerebral infarction, angina pectoris
  • the medicament of the present invention can enhance the platelet aggregation inhibitory action of aspirin
  • diseases using aspirin for the purpose of inhibiting platelet aggregation such as heart failure, myocardial infarction, cerebral infarction, angina pectoris, arteriosclerosis, Aspirin used in combination with prevention and / or treatment of a disease selected from the group consisting of peripheral arterial occlusions can enhance the effect of prevention and / or treatment of the disease.
  • reperfusion therapy coronary artery bypass, percutaneous coronary intervention, thrombolysis, etc.
  • the administration route of the medicament of the present invention is not particularly limited, and can be administered orally or parenterally.
  • the medicament of the present invention can be orally administered prophylactically to prevent the onset of the above-mentioned diseases, and can be administered prophylactically during or before surgery by parenteral administration such as injection or infusion. You can also.
  • it can be administered to a patient who has developed the above diseases by injection into a vein, artery or heart for the purpose of preventing the deterioration of the symptoms or reducing the symptoms.
  • the dosage form of the medicament of the present invention is not particularly limited, and aspirin, which is the first active ingredient, and the second active ingredient are combined at the time of administration!
  • dosage forms include (1) administration of a single preparation obtained by simultaneously formulating the first active ingredient and the second active ingredient, and (2) first active ingredient and the second active ingredient. Obtained by separately formulating the active ingredients of (3) Sequential administration of two preparations obtained by separate formulation of the first active ingredient and the second active ingredient through the same administration route (4) Simultaneous administration of two different preparations obtained by separately formulating the first active ingredient and the second active ingredient through different administration routes, (5) First active ingredient and second active ingredient There are two types of preparations obtained by formulating the active ingredient separately and sequential administration by different administration routes.
  • the first active ingredient and the second active ingredient may be administered in any order.
  • the first active ingredient and the second active ingredient are separately used as oral preparations such as tablets, and the oral preparations are administered simultaneously or sequentially.
  • the "combination" medicament of the present invention refers to a medicament having a dosage form in which the first active ingredient aspirin and the second active ingredient compound are combined, and from the above (1) Including the case according to the administration form (5).
  • the term “used in combination” includes the cases of the above-mentioned application forms (1) to (5).
  • the compound shown in the following examples is 5 methyl-2 (piperazine 1yl) benzenesulfonic acid monohydrate (hereinafter referred to as caldaret monohydrate).
  • Platelet aggregation is determined by HEMA TRACER 801 (MC MEDICAL) according to the turbidimetric method (Bom, GVR, Cross, MJ., J. Physiol., 168, 178-195, 1963). The product was monitored for 6 minutes after collagen stimulation. PPP was used as a blank.
  • the degree of aggregation was expressed as a percentage of the maximum aggregation amplitude.
  • the results were expressed as the inhibition rate (%) of collagen-induced aggregation according to the following formula.
  • Percent inhibition (%) Maximum aggregation amplitude of control
  • MCC-135 The effect of the drug (MCC-135) was analyzed by 95% confidence interval (95% C. I). All data are expressed as mean soil standard error (MEAN soil SEM).
  • Figure 1 shows the platelet aggregation inhibitory effect of aspirin and caldaret monohydrate. Aspirin alone had a dose-dependent inhibitory effect on collagen-induced platelet aggregation, whereas caldaret monohydrate alone had no such inhibitory effect (Fig. 1). .
  • Figure 2 shows the effect of caldaret monohydrate on the antiplatelet aggregation activity of aspirin.
  • Caldaret monohydrate improved the antiplatelet aggregation activity of aspirin ( Figure 2).
  • Karudaretto monohydrate has been to improve the low concentrations of aspirin (3 X 10- 5 M, 1 X 10- 4 M) of the anti-platelet aggregation activity, higher concentrations of aspirin (3 X 10- In 4 M), the activity was not improved (Table 10).
  • This result shows that caldaret monohydrate has a blood serum of aspirin. It has the effect of enhancing the ability to suppress plate aggregation, suggesting that the use of caldaret monohydrate in combination can reduce the dose of aspirin.
  • the rat heart was removed and Krebs buffer (in mM; NaCl 119, C1 4.6, MgSO-7H O 1.2, CaCl-2H O 1.3, NaHCO 25, H PO 1.2, g) according to the Langendorff method.
  • the rat heart is removed and the Kreps buffer (in mM; NaCl 119, C1 4.6, MgSO ⁇ 7 ⁇ O 1.2, CaCl-2H O 1.3, NaHCO 25, KH PO 1.2, glucose according to the Langendorff method.
  • the medicament of the present invention is useful for the prevention and / or treatment of diseases in which aspirin is used for the purpose of inhibiting platelet aggregation.

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  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Surgery (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne un agent pharmaceutique efficace dans la prévention et/ou le traitement d'une maladie associée à la formation d'un thrombus ou d'un embole ou d'une maladie induite par la formation d'un thrombus ou d'un embole. Cet agent pharmaceutique comprend une combinaison d'aspirine et n'importe lequel des composés (a) à (d) suivants: (a) un composé capable d'agir sur une protéine de gestion du calcium en vue de moduler le niveau de calcium intracellulaire ou son taux de modification; (b) un composé capable d'inhiber la suraccumulation d'un ion calcium dans une cellule; (c) un composé capable d'inhiber la suraccumulation d'un ion sodium dans une cellule; et (d) un dérivé d'acide aminobenzènesulphonique représenté par la formule générale (I), un sel de celui-ci, ou un hydrate ou un solvate de ce dérivé ou de ce sel. Dans la formule générale (I), R1 représente un groupe alkyle en C1-C6 ou analogue; R2 représente un atome d'hydrogène ou analogue; et n représente un entier entre 1 et 4.
PCT/JP2007/067910 2006-09-14 2007-09-14 Agent pharmaceutique contenant de l'aspirine WO2008032814A1 (fr)

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JP2008534401A JPWO2008032814A1 (ja) 2006-09-14 2007-09-14 含アスピリン医薬

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH037263A (ja) * 1989-03-27 1991-01-14 Mitsubishi Kasei Corp アミノベンゼンスルホン酸誘導体
JPH04139127A (ja) * 1990-09-27 1992-05-13 Mitsubishi Kasei Corp 心疾患を予防または治療する薬剤
JPH09221479A (ja) * 1995-12-15 1997-08-26 Mitsubishi Chem Corp アミノベンゼンスルホン酸誘導体一水和物及びその製造方法
WO2004019946A1 (fr) * 2002-08-30 2004-03-11 Mitsubishi Pharma Corporation Inhibiteurs de l'accumulation excessive d'ions sodium dans les cellules

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH037263A (ja) * 1989-03-27 1991-01-14 Mitsubishi Kasei Corp アミノベンゼンスルホン酸誘導体
JPH04139127A (ja) * 1990-09-27 1992-05-13 Mitsubishi Kasei Corp 心疾患を予防または治療する薬剤
JPH09221479A (ja) * 1995-12-15 1997-08-26 Mitsubishi Chem Corp アミノベンゼンスルホン酸誘導体一水和物及びその製造方法
WO2004019946A1 (fr) * 2002-08-30 2004-03-11 Mitsubishi Pharma Corporation Inhibiteurs de l'accumulation excessive d'ions sodium dans les cellules

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MIZOGUCHI H. ET AL.: "Igaku no Ayumi Ketsueki Shikkan -State of Arts", 25 October 1993, ISHIYAKU PUB., INC., pages: 295 - 297, XP003021710 *

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