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
  • A61K31/185—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
  • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• • 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
  • A61P9/10—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 method for the prevention or reduction of cardiovascular events associated with coronary intervention.
• the method comprises administrating to a mammal, particularly a human patient, after coronary intervention an oral or parental dose of N-(3',4 '- dimethoxycinnamoy anthranilic acid (N-5 1 ) (Tranilast) represented by the following formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.
• N-5 1 dimethoxycinnamoy anthranilic acid
• Coronary intervention is a percutaneous procedural approach to the treatment of ischemic heart disease such as angina pectoris and myocardial infarction.
• Coronary intervention technically involves mechanical revascularization of a stenosed lesion in a coronary artery by means of a balloon catheter, stent placement, an atherectomy catheter and the like.
• coronary intervention often causes restenosis due to damaged intima and media cells. Patients who experience restenosis may require revascularization procedures to correct the condition.
• Other cardiovascular events associated with coronary intervention include myocardial infarction and death.
• Tranilast is sold commercially as a drug for the treatment of allergic diseases, e.g., allergic bronchitis, allergic asthma, atopic dermatitis, and the like, based on the activity exhibited by the drug for inhibiting release of chemical mediators [The Journal of Allergy and Clinical Immunology, Vol. 57, No. 5, pp. 396-407, (1976)].
• the 935 patent demonstrated that an extended period of Tranilast treatment was effective for lowering the incidence of post-surgery restenosis associated with PTCA. It was found that dosing patients with Tranilast for a period of at least about three months (i.e., a term of at least about 90 consecutive days of treatment, as used herein the phrase "at least three consecutive months" means at least 90 days) reduced the incidence of restenosis associated with the PTCA procedure. In one clinical study, when patients were administered Tranilast in a daily oral dose of 600 mg for three consecutive months after the PTCA procedure, the incidence of restenosis was less than about 20%. As reported in the 935 patent, the incidence of restenosis associated with the PTCA procedure usually is about 40%. The 935 patent does not contain any disclosure regarding the ability of Tranilast to effect cardiovascular events as defined herein.
• Tranilast could be efficaciously administered for the prevention or reduction of cardiovascular events associated with coronary intervention. It has now surprisingly been discovered that Tranilast can be suitably administered in the prevention or reduction of cardiovascular events associated with coronary intervention.
• This invention relates to a method for the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, which comprises administering to the subject N-(3',4'-dimethoxycinnamoyl)anthranilic acid (N-5 7 ) or a pharmaceutically acceptable salt thereof in a daily dose of from about 300 mg to about 1,100 mg in association with coronary intervention.
• This invention further relates to a method for the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, which comprises administering to the subject N-(3',4 - dimethoxycinnamoyl)anthranilic acid (N-5 or a pharmaceutically acceptable salt thereof in a daily dose of from about 300 mg to about 1,100 mg for a treatment period of at least three consecutive months in association with coronary intervention.
• N-5 N-(3',4 - dimethoxycinnamoyl)anthranilic acid
• inorganic salts such as sodium or calcium salt, or organic salts formed with amines such as morpholine, piperidine, arginine, and the like.
• PTCA Percutaneous Transluminal Coronary Angioplasty
• Directional Coronary Atherectomy and Stent placement can be included.
• cardiovascular events is preferably meant myocardial infarction and death associated with coronary intervention. Also included in the term cardiovascular events is the need for revascularization procedures associated with coronary intervention. By the phrase “prevention or reduction” of cardiovascular events as used herein, is meant that the incidence of myocardial infarction and/or death and/or the need for revascularization procedures associated with coronary intervention in Trailast treated patients are prevented or reduced in comparison to untreated patients.
• association with coronary intervention is meant that the treatment with Tranilast can commence immediately, for example within 4 to 8 hours, after coronary intervention, within a few days, for example 2 days, after coronary intervention or for a period of several days, for example about 7 days, prior to coronary intervention. Also contemplated within the phrase “in association with coronary intervention” is a dosing protocol in which a dose or several doses are skipped, for example in the morning of or on the day of coronary invention.
• collected over the observation period means a period of up to 12 months.
• the present invention relates to a method for the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, which comprises administering to the subject N-(3',4'- dimethoxycinnamoyl)anthranilic acid (N-5') (Tranilast) or a pharmaceutically acceptable salt thereof in a daily dose of from about 300 mg to about 1,100 mg in association with coronary intervention.
• the present invention further relates to a method for the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, which comprises administering to the subject N-(3',4'- dimethoxycinnamoyl)anthranilic acid (N-5 1 ) (Tranilast) or a pharmaceutically acceptable salt thereof in a daily dose of from about 300 mg to about 1,100 mg for a treatment period of at least three consecutive months in association with coronary intervention.
• a preferred daily dosage amount of Tranilast for use in the present invention is about 400 mg to about 1,000 mg.
• a more preferred daily dosage amount of Tranilast for use in the present invention is from about 500 mg to about 900 mg.
• the most preferred daily dosage amount of Tranilast for use in the present invention is from about 600 mg to about 900 mg.
• Particularly preferred is a daily dosage amount of about 600 mg of Tranilast for use in the present invention.
• Particularly preferred is a daily dosage amount of about 900 mg of Tranilast for use in the present invention.
• a contemplated treatment period for use in the present invention is about 60 days in association with coronary intervention.
• An additional contemplated treatment period for use in the present invention is about 45 days in association with coronary intervention.
• a preferred treatment period for use in the present invention is about 30 days in association with coronary intervention.
• An additional contemplated treatment period for use in the present invention is 14 days in association with coronary intervention.
• a preferred method of use in the current invention is a method for preventing or reducing myocardial infarction associated with coronary intervention.
• a preferred method of use in the current invention is a method for preventing or reducing death associated with coronary intervention.
• a preferred method of use in the current invention is a method for preventing or reducing the need for revascularization procedures associated with coronary intervention.
• the present invention therefor provides a method for the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, which comprises administering to the subject N-(3',4 - dimethoxycinnamoyl)anthranilic acid (N-5 (Tranilast) or a pharmaceutically acceptable salt thereof in a daily dose of from about 300 mg to about 1 , 100 mg in association with coronary intervention.
• N-5 Trimethoxycinnamoyl)anthranilic acid
• a pharmaceutically acceptable salt thereof in a daily dose of from about 300 mg to about 1 , 100 mg in association with coronary intervention.
• the present invention further provides a method for the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, which comprises administering to the subject N-(3',4 - dimethoxycinnamoyl)anthranilic acid (N-5 (Tranilast) or a pharmaceutically acceptable salt thereof in a daily dose of from about 300 mg to about 1, 100 mg for a treatment period of at least three consecutive months in association with coronary intervention.
• N-5 Trimethoxycinnamoyl)anthranilic acid
• the invention also provides for the use of Tranilast or a pharmaceutically acceptable salt thereof in the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, in a daily dose of from about 300 mg to about 1,100 mg in association with coronary intervention.
• the invention further provides for the use of Tranilast or a pharmaceutically acceptable salt thereof in the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, in a daily dose of from about 300 mg to about 1,100 mg for a treatment period of at least three consecutive months in association with coronary intervention.
• the invention also provides for a pharmaceutical composition for use in the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, which comprises Tranilast or a pharmaceutically acceptable salt thereof in a daily dose of about 300 mg to about 1,100 mg in association with coronary intervention.
• the invention further provides for a pharmaceutical composition for use in the prevention or reduction of cardiovascular events associated with coronary intervention in a mammal, particularly a human, which comprises Tranilast or a pharmaceutically acceptable salt thereof in a daily dose of about 300 mg to about 1,100 mg for a treatment period of at least three consecutive months in association with coronary intervention.
• Tranilast is generally described in United States Patent 3,940,422. Tranilast and pharmaceutically acceptable salts and compositions thereof can be readily prepared by known methods such as described in United States Patent 3,940,422.
• Tranilast or a pharmaceutically acceptable salt thereof When Tranilast or a pharmaceutically acceptable salt thereof is employed therapeutically, it can be administered orally or parentally in appropriate dosage forms, such as powder, granules, tablets, capsules, injectable solutions, and the like.
• a Tranilast pharmaceutical composition can be formulated by admixing suitable carriers such as excipients, disintegrators, binders, brighteners, and the like, and preparing in accordance with conventional molding methods and dosage forms.
• a powdered dosage form can be formulated by admixing Tranilast of a pharmaceutically acceptable salt thereof with suitable excipients, binders, brighteners, and the like.
• Tablets can be formulated by admixing Tranilast or a pharmaceutically acceptable salt thereof with suitable excipients, disintegrators, binders, brighteners, and the like, and compressing the mixture with conventional molding equipment.
• the tablets also can be coated to provide film coated tablets, sugar-coated tablets, enteric-coated tablets, and the like.
• Capsules can be formulated by admixing Tranilast or a pharmaceutically acceptable salt thereof thereof with suitable excipients, brighteners, and the like, and filling the mixture in capsules, or by forming granules containing Tranilast or a pharmaceutically acceptable salt thereof with conventional molding equipment, and filling the formed granules in capsules.
• the daily dosage of Tranilast or a pharmaceutically acceptable salt thereof as an active ingredient will be an efficacious, nontoxic quantity selected from the range of about 300 mg to about 1,100 mg of active compound, preferably from about 500 mg to about 900 mg of active compound, particularly preferred is a dosage of about 600 mg, particularly preferred is a dosage of about 900 mg, per adult patient preferably by oral administration in association with coronary intervention.
• a treatment period of at least three consecutive months is also contemplated herein.
• the dosage and term of administration can be changed depending upon the weight and age and sex of the patient, the severity of the condition to be treated, and the like.
• the above indicated dose may be split and administered preferably from 1-6 times daily, preferably about 2 times a day, orally or parenterally.
• Preferred forms of parenteral administration include topically, rectally, transdermally, by injection and continuously by infusion. Oral administration is preferred.
• Optimal dosages to be administered may be readily determined by those skilled in the art, and will vary with the strength of the preparation, the mode of administration, and the advancement of the disease condition. Additional factors depending on the particular patient being treated will result in a need to adjust dosages, including patient age, weight, diet, and time of administration.
• groups may also be given a calcium antagonist, nitrates and/or anti-platelet agents. These drugs are administered for 3 consecutive months after PTCA.
• the comparative clinical data collected over the observation period demonstrate the efficacy of 3 month Tranilast treatment for the prevention or reduction of incidence of death in patients after the PTCA procedure.
• groups may also be given a calcium antagonist, nitrates and/or anti-platelet agents. These drugs are administered for 3 consecutive months after PTCA.
• groups may also be given a calcium antagonist, nitrates and/or anti-platelet agents. These drugs are administered for 30 consecutive days after PTCA.
• the comparative clinical data collected over the observation period demonstrate the efficacy of 30 days Tranilast treatment for the prevention or reduction of incidence of myocardial infarction in patients after the PTCA procedure.
• groups may also be given a calcium antagonist, nitrates and/or anti-platelet agentss. These drugs are administered for 30 consecutive days after PTCA.
• groups may also be given a calcium antagonist, nitrates and/or anti-platelet agents. These drugs are administered for 30 consecutive days after PTCA.
• the comparative clinical data collected over the observation period demonstrate the efficacy of 30 days Tranilast treatment for the prevention or reduction the need for revascularization procedures in patients after the PTCA procedure.

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• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Cardiology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Epidemiology (AREA)
• Heart & Thoracic Surgery (AREA)
• Urology & Nephrology (AREA)
• Vascular Medicine (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)

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• 2000
  • 2000-02-02 JP JP2000596930A patent/JP2002536326A/ja not_active Withdrawn
  • 2000-02-02 CA CA002361578A patent/CA2361578A1/en not_active Abandoned
  • 2000-02-02 HU HU0200148A patent/HUP0200148A3/hu unknown
  • 2000-02-02 PL PL00349926A patent/PL349926A1/xx not_active Application Discontinuation
  • 2000-02-02 KR KR1020017009743A patent/KR20010101933A/ko not_active Application Discontinuation
  • 2000-02-02 BR BR0007901-4A patent/BR0007901A/pt not_active Application Discontinuation
  • 2000-02-02 AU AU29785/00A patent/AU2978500A/en not_active Abandoned
  • 2000-02-02 CN CN00803386A patent/CN1338930A/zh active Pending
  • 2000-02-02 AR ARP000100437A patent/AR022475A1/es unknown
  • 2000-02-02 TR TR2001/02262T patent/TR200102262T2/xx unknown
  • 2000-02-02 MX MXPA01007833A patent/MXPA01007833A/es unknown
  • 2000-02-02 WO PCT/US2000/002611 patent/WO2000045810A1/en not_active Application Discontinuation
  • 2000-02-02 EP EP00908440A patent/EP1180027A4/en not_active Withdrawn
  • 2000-02-02 IL IL14471900A patent/IL144719A0/xx unknown
  • 2000-02-03 CO CO00006605A patent/CO5160246A1/es unknown
• 2001
  • 2001-07-31 ZA ZA200106297A patent/ZA200106297B/en unknown
  • 2001-08-02 NO NO20013789A patent/NO20013789L/no not_active Application Discontinuation

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