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
  • A61K31/33—Heterocyclic compounds
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide

Definitions

• the present invention relates to the field of organic chemistry and more particularly to that of therapeutic chemistry.
• compositions formed from a combination of a specific beta-blocking agent and amiodarone in low doses so as to avoid or limit the occurrence of annoying side effects.
• beta-blocking agents have significant anti-arrhythmic and anti-isch ⁇ mic activity, at the usual doses, but they have the drawback of triggering significant side effects.
• Amiodarone for its part, is an effective antiarrhythmic agent but whose sensitive side effects considerably limit its use. In general, the combination of a beta-blocker and amiodarone is contraindicated and this mention appears in all official dictionaries ⁇ cf. VIDAL).
• Angina disease is the result of a mismatch between the heart's oxygen supply and the heart's oxygen requirements.
• Current angina pectoris drugs have remarkable efficacy, but it is not always possible with these drugs to prevent both exertional pain and exertional arrhythmias without inducing undesirable side effects. Reducing arrhythmias during exercise is important because such arrhythmias can lead to death.
• the objective of the invention is the creation of a very effective angina pectoris drug also possessing a certain anti-arrhythmic activity but devoid of certain side effects such as disorders of sexual function.
• beta-blocker drugs cause headaches so intense that they stop the medication.
• beta-blockers induce peripheral disorders, fatigue or depression EXPERIENCE
• the beta-blocking agent selected and amiodarone paradoxically, manifest a synergistic action at these doses, which makes it possible to eliminate any side effect.
• the daily dose of amiodarone thus administered is low enough so that the side effects which it possibly causes are considerably reduced.
• the product alone containing the lower dose of amiodarone was designed from the quality of life scale focused on your relationship between pain and exertion. The development of this scale allowed the determination of the optimal dose.
• the pharmaceutical compositions according to the invention significantly shift the curve of the symptoms to the left. This displacement is greater than that observed with a nitro derivative and with a calcium antagonist.
• the invention therefore consists of new pharmaceutical compositions combining amiodarone at low doses and a blocking agent chosen from the group consisting of betaxolol and its addition salts at low doses, in combination or in mixture with an excipient or a inert non-toxic, pharmaceutically acceptable vehicle.
• the invention therefore relates to new pharmaceutical compositions formed from a combination based on Amiodarone and a beta-blocker, characterized in that the beta-blocker is chosen from the group consisting of betaxolol and its salts. addition with a therapeutically compatible mineral or organic acid.
• the hydrochloride effectively used in the form of a pharmaceutical specialty.
• nitrate, phosphates, acetate, propionate, citrates, tartrates, malates, gluconates or glucose 1-phosphate find equivalent use.
• the pharmaceutical compositions contain from 25 mg to 400 mg per unit dose of Amiodarone and more particularly from 50 mg to 100 mg.
• the dose of betaxolol or one of its salts ranges from 2.5 mg to 75 mg per unit dose and preferably from 5 mg to 25 mg per dose. It can be lowered for intravenous administration at a dose as low as 0.5 mg.
• the pharmaceutical compositions contain 100 mg of amiodarone and 10 mg of betaxolol or one of its salts with a therapeutically compatible mineral or organic acid.
• beta-blocking agent the racemic molecule or a split molecule, optically active.
• the optically active forms of beta-blocking agents exhibit the same level of activity as the racemic molecule, but on the other hand, their activity is purer, that is to say that their administration leads to fewer side effects. .
• compositions according to the invention are intended essentially for oral administration. However, parenteral or rectal administration may be considered.
• the most suitable forms for these routes of administration are ampoules, multidose vials, auto-injectable syringes, lyophilisates to be reconstituted with a solvent for use, bare or coated tablets, dragees, capsules, soft capsules, pills, granules, powders flavored or not, sweetened or not, suppositories or rectal capsules.
• the appropriate inert excipient is chosen from those which are suitable for oral or rectal administration such as starches, celluloses, alkyl DClubse, carboxymethy! cellulose, lactose, calcium carbonate, calcium phosphate, magnesium phosphate, magnesium carbonate, alumina, silica, calcium silicate, magnesium silicate or talc.
• Dispersing agents, disintegrating agents, release agents, binding agents or compression agents can be added thereto.
• cocoa butter or semi-synthetic triglycerides or polyethylene glycol stearates are used as vehicle.
• sugar syrup, distilled water, physiological serums, lipid emulsions or even dispersions of surfactants, nonionic agents, and generally isotonic preparations are preferably used.
• the invention also relates to a process for obtaining the pharmaceutical compositions defined above.
• the pharmaceutical forms according to the invention are prepared according to the usual methods of manufacture in the pharmaceutical field.
• This product can be administered as a loading dose in the presence of severe tachycardia such as, for example, Bouveret tachycardia or a severe angina attack with ventricular extrasystoles and tachycardia.
• severe tachycardia such as, for example, Bouveret tachycardia or a severe angina attack with ventricular extrasystoles and tachycardia.
• the doctor can administer the ideal product as maintenance treatment with a daily dose of Amiodarone of 150 mg and a dose of Betaxolol of 10 mg.
• the optimal product according to the invention used in the emergency treatment of acute myocardial infarction, acute ventricular tachycardia, multiple ventricular extrasystoles and tachycardia in the presence of ischemic heart disease is an intravenous form containing 0.5 mg betaxolol and 25 mg amiodarone intended to be administered within 1 to 2 minutes and which may be repeated if the tachycardia persists or until the expected results are obtained.
• DIAGRAM 1 comparison to amiodarone
• DIAGRAM 3 comparison to isosorbid ⁇ dinitrate
• the new drug has fewer side effects than amiodarone and betaxolol taken alone, according to the attached table.
• the product according to the invention is exceptionally effective on two major parameters of angina pectoris (number of angina pains and duration of painless walking). These differences are statistically significant.
• the product according to the invention has no major side effects.

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• 1996
  • 1996-02-02 EP EP96902328A patent/EP0818997A1/de not_active Withdrawn
  • 1996-02-02 WO PCT/FR1996/000175 patent/WO1997027850A1/fr not_active Application Discontinuation

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