WO2005027896A1 - 併用医薬 - Google Patents
併用医薬 Download PDFInfo
- Publication number
- WO2005027896A1 WO2005027896A1 PCT/JP2004/013982 JP2004013982W WO2005027896A1 WO 2005027896 A1 WO2005027896 A1 WO 2005027896A1 JP 2004013982 W JP2004013982 W JP 2004013982W WO 2005027896 A1 WO2005027896 A1 WO 2005027896A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- thromboembolism
- group
- medicament according
- ethyl
- amidino
- Prior art date
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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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- 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
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
-
- 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
- A61P9/10—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 comprising a combination of an antiplatelet drug and a 5-amidino1-2-hydroxybenzenesulfonamide derivative or a pharmacologically acceptable salt thereof.
- the present invention relates to an antiplatelet agent and a direct and selective inhibitor of activated blood coagulation factor X (hereinafter referred to as factor Xa),
- R is a hydrogen atom or a lower alkyl group and Z is a hydrogen atom or a hydroxyl group
- a pharmacologically acceptable salt thereof It relates to a medicine obtained by combining the above.
- thrombosis-related diseases include thromboembolism caused directly or indirectly by the formation of thrombus inside blood vessels.1) For example, unstable angina, myocardial infarction, cerebral thrombosis, etc. A disease (thrombosis) caused by the formation of blood clots that gradually become larger and blood does not flow further ahead. 2) For example, formed thrombus such as economy class syndrome and cardiogenic cerebral embolism get on the bloodstream. Disease caused by clogging blood vessels ahead ) (Non-Patent Document 1).
- thromboembolisms are caused by two causes: thrombus or embolus.Thus, merely improving the blood flow at the site of occlusion may not always produce a satisfactory effect. It is important to control growth and transport.
- aspirin, cilostazol, dipyridamole, ticlovidine, clopidogrel and the like are used as antiplatelet drugs for the prevention and treatment of thromboembolism.
- antiplatelet drugs inhibit platelet activation and have the risk of bleeding tendency (Non-Patent Documents 2 and 3)
- the use of antiplatelet drugs is expected to be increased in expectation of the effect of suppressing thrombus formation. Therefore, further improvement is required as a preventive or therapeutic agent for thromboembolism.
- DX-9605a represented by the formula (A), which is a direct factor Xa inhibitor, or a formula Xa, which is a direct factor Xa inhibitor
- YM represented by 2HC1 — 608 28 or a direct factor Xa inhibitor, general formula:
- the factor Xa inhibitor proposed in the above combination examples is an indirect factor Xa inhibitor having a completely different inhibition mechanism from the direct factor Xa inhibitor of the present invention, or In the general formula (I) according to the present invention, It is a drug whose chemical structure is significantly different from the indicated 5-amidino-2-hydroxybenzenesulfonamide derivative.
- the only effect observed in the above combination example is the effect of improving blood flow at the site of thrombus formation in a model of arterial thrombosis, and, as in the present invention, 1) reduction of the amount of thrombus formation Effect, 2) No improvement effect on the hypercoagulable state has been reported.
- the combination of the anti-platelet drug and the 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula (I) of the present invention is suitable for the prevention or treatment of thromboembolism. It is not known at all.
- An object of the present invention is to provide a concomitant drug excellent in the effect of preventing or treating thromboembolism.
- the present inventors have conducted intensive studies in view of the above problems, and as a result, have found that 1) synergistically, by using an antiplatelet drug in combination with a certain 5-amidino-2-hydroxybenzenesulfonamide derivative. It has been found that two remarkable effects are exhibited: an enhanced effect of reducing the amount of formed thrombus, and 2) an excellent effect of improving the hypercoagulable state, which is not observed when used alone. As a result of repeated studies based on these findings, the present inventors have led to the present invention. It was.
- a medicine comprising a combination of an antiplatelet agent and a 5-amidinol 2-hydroxybenzenesulfonamide derivative represented by the above general formula (I) or a pharmaceutically acceptable salt thereof;
- the antiplatelet drug is a compound selected from the group consisting of aspirin, dipyridamole, cilostazol, ticulovidin, and clopidogrel.
- the combination of an antiplatelet drug with the 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the above general formula (I) has a synergistic enhancement of 1). It has the effect of reducing the amount of thrombus formation, and 2) has an excellent effect of improving the state of hypercoagulability, which is not observed when used alone, and is an extremely suitable drug for patients with a wide range of thromboembolism.
- the medicament of the present invention can sufficiently prevent or treat thromboembolism without increasing the amount of antiplatelet drugs, or can reduce the amount of antiplatelet drugs used. It is an excellent medicine that can reduce the risk that has been a concern in the past, so that patients can use antiplatelet drugs more safely and safely.
- the antiplatelet agents of the present invention include: 1) arachidonic acid metabolism inhibitors (eg, aspirin, ozadarel, icosapentate ethyl, dilazep), 2) ADP receptor inhibitors (eg, ticlovidine, clopidogrel, prasdarell), 3) glyco Protein IIIIa antagonists (eg, Abciximab, eptifibatide, tylofipan, ramifan), 4) phosphodiesterase inhibitors ('e.g., cilostazol, dipyridamole, etc.), 5) adenylsyl cyclase activators (e.g., beraprost sodium, ticlovidin, limaprost, veraprost, 6) serotonin 5-HT 2 receptor antagonist (for example, sarpogrelate), 7) thromboxane A 2 receptor antagonist (for example, S-18204), among others, aspirin, ticlovidine
- the lower alkyl group means a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a pentyl group, an isopentyl group, A linear or branched alkyl group having 1 to 6 carbon atoms, such as a neopentyl group, a 1-methylbutyl group, a 2-methylbutyl group, a hexyl group, etc., with n-butyl group being most preferred.
- Z is preferably a hydroxyl group, and compounds having a hydroxyl group and pharmacologically acceptable salts thereof are compounds having good oral absorption.
- the pharmacologically acceptable salt includes, for example, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid Salts with mineral acids such as acid, acetic acid, phosphoric acid, etc., formic acid, acetic acid, methanesulfonic acid, benzenesulfonic acid, P-tosylsulfonic acid, propionic acid, citric acid, succinic acid, tartaric acid, fumaric acid, butyric acid, oxalic acid Salts with organic acids such as malonic acid, maleic acid, maleic acid, lactic acid, malic acid, carbonic acid, glutamic acid, aspartic acid, salts with organic bases such as morpholine, pyrrolidine, piperidine, piperazine, lysine, sodium salt And salts with inorganic bases such as potassium salt and calcium salt.
- the compound represented by the general formula (1) also includes hydrates and solvates with pharmaceutically acceptable solvents such as ethanol.
- examples of preferred combinations include, for example,
- Prevention of thromboembolism in the present invention includes not only prevention of the onset of the first onset but also prevention of its recurrence.
- the treatment of thromboembolism is the improvement of the onset However, it also includes the prevention or worsening of the onset condition.
- Arterial thrombosis unstable angina, myocardial infarction, cerebral thrombosis, atherothrombotic cerebral infarction, lacunar infarction, chronic arterial occlusion, peripheral arterial occlusion, coronary artery intervention (for example, coronary artery balloon surgery, coronary artery Occlusion due to stent implantation, coronary atherectomy, etc., occlusion after vascular or valve replacement, etc .;
- Arterial embolism cardiogenic cerebral embolism, lacunar infarction, chronic arterial occlusion, obstructive arteriosclerosis, transient ischemic attack, coronary artery intervention (eg, coronary artery balloon plastic surgery, coronary artery Occlusion due to stent implantation, coronary artery resection, etc., occlusion after vascular replacement or prosthetic valve replacement;
- coronary artery intervention eg, coronary artery balloon plastic surgery, coronary artery Occlusion due to stent implantation, coronary artery resection, etc., occlusion after vascular replacement or prosthetic valve replacement;
- Venous thrombosis deep vein thrombosis, sinus thrombosis, post-thrombotic thrombotic syndrome, etc .;
- Venous embolism Thrombosis, pulmonary obstruction, deep vein thrombosis, post-thrombotic syndrome caused by thrombus, etc., including Economy class syndrome.
- the medicament of the present invention is an excellent medicament useful for both thrombotic and embolic diseases, and can be used for a wide range of patients with thromboembolism.
- the 5-amidino 2-hydroxybenzenesulfonamide derivative represented by the general formula (I) or a pharmacologically acceptable salt thereof according to the present invention is, for example, International Publication No. 02Z28882. It can be produced by the method described in No. 7 pamphlet or a method analogous thereto.
- the medicament of the present invention is a combination of an antiplatelet agent and a 5-amidinol 2-hydroxybenzenesulfonamide derivative represented by the above general formula (I) or a pharmacologically acceptable salt thereof.
- Yes including both simultaneous administration as a single product, simultaneous administration of the same or different routes as separate products, and staggered administration of the same or different routes as separate products. It is a thing.
- the above-mentioned administration at staggered intervals refers to administration of an antiplatelet agent and a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula (I) or a pharmacologically acceptable salt thereof, respectively.
- the frequency may be the same or different, but both must be used to achieve the desired prophylactic or therapeutic effect. It is desirable to administer in close time.
- the order of administration can be appropriately determined according to the type of drug used in combination.
- the present invention obtained by combining an antiplatelet agent with a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the above general formula (I) or a pharmacologically acceptable salt thereof.
- a pharmaceutical composition comprising an antiplatelet drug-containing pharmaceutical composition and a 5 -amidino-2-hydroxybenzenesulfonamide derivative represented by the above general formula (I) or a pharmacologically acceptable salt thereof
- a kit comprising the composition
- the administration route of the medicament of the present invention is not particularly limited, and may include an antiplatelet agent and a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the above general formula (I) or a pharmacologically acceptable salt thereof.
- the preparation for oral administration include powders, granules, tablets, capsules and dry syrups
- parenteral administration include injections, suppositories, patches and the like.
- pharmacologically acceptable carrier various organic or inorganic carrier substances commonly used as a drug substance are used, and in accordance with a usual pharmacological technique, an appropriate excipient, disintegrant, Binders, lubricants, diluents, buffers, isotonic agents, wetting agents, emulsifiers, dispersants, stabilizers, solubilizers, surfactants, solubilizers, pH regulators, preservatives , Preservatives, antioxidants, coloring agents, sweetening agents, etc., and can be formulated.
- powders or granules may be added to the active ingredient, if necessary, with appropriate excipients, lubricants, etc., and thoroughly mixed to give a powder or granules.
- Tablets are prepared by adding appropriate excipients, disintegrants, binders, lubricants and the like, if necessary, to the active ingredient and compressing the tablets in a conventional manner. If necessary, the composition may be appropriately coated to give film-coated tablets, sugar-coated tablets, enteric-coated tablets and the like. Capsules are added to the active ingredient, if necessary, with appropriate excipients, lubricants, and the like, mixed well, or formed into granules or fine granules by a conventional method, and then filled into suitable capsules. Into capsules.
- an immediate release or sustained release preparation can be prepared depending on the treatment method.
- Injectables if necessary for the active ingredient, appropriate stabilizers, surfactants, solubilizers, buffers, isotonic agents, pH adjusters, isotonic agents, dispersants, preservatives, dissolution Auxiliaries and the like can be appropriately compounded.
- the dose of the medicament of the present invention may be in accordance with the dose of each active ingredient, and is appropriately determined according to the patient's age, body weight, degree of disease, administration time, administration timing, combination of drugs, therapeutic effect, etc. Is done.
- about 150 to 300 mg per day, for aspirin, for oral administration, about 50 to 320 mg per day, for clopidogrel, for oral administration about It can be administered in the range of 50 to 300 mg per day.
- the dose of the compound represented by the general formula (I) used in combination with these antiplatelet drugs is about 1 to 100 mg per day for oral administration, and about 1 day for parenteral administration. It is 0.1 to 500 mg per unit.
- the combined use of the antiplatelet agent and the compound represented by the general formula (I) can enhance the drug efficacy as described above, so that the dose can be appropriately adjusted. Can be reduced.
- Rats (Sprague-Dawley rats, male) were divided into four groups, A, B, C, and D. 0.5% methylcellulose was used for groups A and B, and cilostazol (1) was used for groups C and D. (0.0 mg gZkg) was orally administered. One hour later, it was dissolved in a physiological saline solution containing 0.05 M aqueous sodium hydroxide solution.
- the surface of the abdominal aorta in all groups A to D was contacted with a filter paper (4 x 5 mm) immersed in 50% ferric chloride solution for 5 minutes to form thrombi. Provoked.
- the abdominal aorta was ligated with sutures at the upper and lower portions of the thrombus induction site, respectively, and then removed. All the thrombus adhering to the inside of the abdominal aorta extracted was collected and dissolved in 1 mL of a 0.05 M aqueous sodium hydroxide solution to prepare a test solution.
- the total amount of protein in the thrombus dissolved in the test solution was quantified using the Coomasie Plus Protein Assay Kit (PI ERC E), and this was used as an indicator of the amount of thrombus formation.
- Blood was collected from ⁇ heron (Japanese white species, male), and the blood left at room temperature for 30 to 60 minutes was used as the whole blood.
- Activated whole blood coagulation time measurement tube Hemocron Test Tube 12, International Technology Co., Ltd.
- the activated whole blood clotting time was measured using a blood coagulometer (Hemocron 811, International Techidyne Corporation) as a control. .
- Table 2 shows the results. Neither aspirin, dipyridamole, or syrosol alone at 1 M alone had a significant prolonged effect on activated whole blood clotting time relative to controls (B-D in Table 2). In addition, Compound Id alone at 0.1; ⁇ did not show a significant prolonged effect on the activated whole blood clotting time as compared with the control ( ⁇ in Table 2).
- the medicament of the present invention in which an antiplatelet drug is combined with a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the above general formula (I) or a pharmacologically acceptable salt thereof may be used.
- a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the above general formula (I) or a pharmacologically acceptable salt thereof may be used.
- anti-platelet drugs can be sufficiently prevented or treated without increasing the amount of antiplatelet drugs used, or the amount of antiplatelet drugs used can be reduced. It is an excellent drug that can reduce the risk of increased bleeding tendency due to the use of platelet drugs, and can be used more safely and safely for antiplatelet drugs for patients.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Vascular Medicine (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)
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/572,515 US20070105825A1 (en) | 2004-09-16 | 2004-09-16 | Concurrent drugs |
JP2005514123A JP4855073B2 (ja) | 2003-09-19 | 2004-09-16 | 併用医薬 |
EP04773372A EP1679067A4 (en) | 2003-09-19 | 2004-09-16 | COMBINED MEDICINES |
CA002538366A CA2538366A1 (en) | 2003-09-19 | 2004-09-16 | Concurrent drugs |
US12/560,733 US20100009939A1 (en) | 2003-09-19 | 2009-09-16 | Concurrent drugs |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003328487 | 2003-09-19 | ||
JP2003-328487 | 2003-09-19 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/560,733 Continuation US20100009939A1 (en) | 2003-09-19 | 2009-09-16 | Concurrent drugs |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005027896A1 true WO2005027896A1 (ja) | 2005-03-31 |
Family
ID=34372901
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2004/013982 WO2005027896A1 (ja) | 2003-09-19 | 2004-09-16 | 併用医薬 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20100009939A1 (ja) |
EP (1) | EP1679067A4 (ja) |
JP (1) | JP4855073B2 (ja) |
CA (1) | CA2538366A1 (ja) |
WO (1) | WO2005027896A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPWO2011065444A1 (ja) * | 2009-11-27 | 2013-04-18 | 学校法人東海大学 | 抗血栓剤 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160004380A1 (en) * | 2014-07-07 | 2016-01-07 | Samsung Electronics Co., Ltd. | Method of performing a touch action in a touch sensitive device |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07258103A (ja) * | 1993-09-13 | 1995-10-09 | Hu Kye Sung | 抗血栓剤及びその製造方法 |
JPH08217692A (ja) * | 1995-02-10 | 1996-08-27 | Nippon Steel Corp | 血管閉塞防止剤 |
JPH0920681A (ja) * | 1995-03-15 | 1997-01-21 | Behringwerke Ag | 血栓溶解処置を受けていない患者におけるヒルジンおよびアセチルサリチル酸による急性心筋梗塞の処置方法 |
JP2002504110A (ja) * | 1997-06-13 | 2002-02-05 | サノフィ−サンテラボ | Xa因子の直接または間接的選択阻害剤の、単独および/または抗血小板凝集活性を有する化合物と組み合わせた動脈血栓塞栓症における治療および予防への組成および使用 |
WO2002028827A1 (fr) * | 2000-10-04 | 2002-04-11 | Kissei Pharmaceutical Co., Ltd. | Derives de 5-amidino-2-hydroxybenzenesulfonamide, compositions pharmaceutiques les contenant et leurs intermediaires de preparation |
WO2003000256A1 (de) * | 2001-06-20 | 2003-01-03 | Bayer Healthcare Ag | Kombinationstherapie substituierter oxazolidinone |
JP2003104957A (ja) * | 2001-09-28 | 2003-04-09 | Kissei Pharmaceut Co Ltd | ビフェニルエチルアミン誘導体およびその製造方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1161279A1 (en) * | 1999-03-11 | 2001-12-12 | Du Pont Pharmaceuticals Company | Treatment of thrombosis by combined use of a factor xa inhibitor and aspirin, tissue plasminogen activator (tpa), a gpiib/iiia antagonist, low molecular weight heparin or heparin |
WO2000053168A2 (en) * | 1999-03-11 | 2000-09-14 | Du Pont Pharmaceuticals Company | Synergy between low molecular weight heparin and platelet aggregation inhibitors, for preventing and treating thromboembolic disorders |
MXPA04009234A (es) * | 2002-03-22 | 2005-01-25 | Kissei Pharmaceutical | Agente preventivo o terapeutico para enfermedades renales. |
-
2004
- 2004-09-16 EP EP04773372A patent/EP1679067A4/en not_active Withdrawn
- 2004-09-16 CA CA002538366A patent/CA2538366A1/en not_active Abandoned
- 2004-09-16 WO PCT/JP2004/013982 patent/WO2005027896A1/ja active Application Filing
- 2004-09-16 JP JP2005514123A patent/JP4855073B2/ja not_active Expired - Fee Related
-
2009
- 2009-09-16 US US12/560,733 patent/US20100009939A1/en not_active Abandoned
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH07258103A (ja) * | 1993-09-13 | 1995-10-09 | Hu Kye Sung | 抗血栓剤及びその製造方法 |
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Also Published As
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JPWO2005027896A1 (ja) | 2006-11-24 |
EP1679067A4 (en) | 2010-04-07 |
JP4855073B2 (ja) | 2012-01-18 |
US20100009939A1 (en) | 2010-01-14 |
CA2538366A1 (en) | 2005-03-31 |
EP1679067A1 (en) | 2006-07-12 |
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