Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
• • 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
  • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/08—Solutions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/04—Centrally acting analgesics, e.g. opioids
• • 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
  • 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 invention relates to a novel formulation of (-) - (1R, 2 "S) -2- (2" -benzyloxy) propyl 4'-hydroxy-5,9,9-trimethyl-6,7-benzomorphan (Bill 890) or one of its pharmacologically acceptable salts, especially its hydrochloride, for parenteral, in particular for intravenous administration, their preparation and use.
• BMI 890 and "active ingredient” is always the compound known from WO 99/14199 (-) - (1 R, 2 "S) -2- (2" -benzyloxy) propyl-4'-hydroxy 5,9,9-trimethyl-6,7-benzomorphan of the formula
• Bill 890 in the form of the free base or the corresponding acid addition salts with pharmacologically acceptable acids, in particular in the form of their hydrochloride.
• Other designations for Bill 890 include crobenetins and [2R- [2,3 (S *), 6]] - 1, 2,3,4,5,6-hexahydro-6,11,11-trimethyl-3- [2 - (phenylmethoxy) propyl] -2,6-methano-3-benzazocin-10-ol.
• Bill 890 is a sodium channel blocker with neuroprotective properties; the main indications are thromboembolic stroke, brain injury and pain.
• the object of the invention is to provide a new formulation for the active ingredient BIM 890, in particular for the hydrochloride thereof.
• the invention relates to pharmaceutical compositions for parenteral administration comprising the active ingredient Bill 890 or one of its physiologically tolerated salts, in particular its hydrochloride, and mannitol as an auxiliary agent. material.
• the amount of mannitol is preferably chosen so that an isotonic solution is obtained.
• the pharmaceutical compositions of the invention also contain other conventional excipients and carriers such as acetic acid / acetate buffer consisting of acetic acid and sodium acetate or sodium acetate trihydrate or a citric acid / phosphate buffer consisting e.g. from citric acid and disodium hydrogen phosphate or disodium hydrogen phosphate dihydrate.
• acetic acid / acetate buffer consisting of acetic acid and sodium acetate or sodium acetate trihydrate
• a citric acid / phosphate buffer consisting e.g. from citric acid and disodium hydrogen phosphate or disodium hydrogen phosphate dihydrate.
• the amount of the buffer components is chosen so that a certain pH and a certain buffer capacity is achieved.
• the solvent is usually water for injections.
• the pharmaceutical composition contains an acetic acid / acetate buffer in addition to the isotonicity of mannitol.
• an acetic acid / acetate buffer in addition to the isotonicity of mannitol.
• Particularly preferred is a 0.005 to 0.05 molar, preferably a 0.005 to 0.02 molar acetic acid / acetate buffer having a pH of 3.8 to 5, most preferably is a 0.01 molar acetic acid / acetate Buffers with a pH of 4.
• Concentration here refers to the total concentration of acetic acid and acetate together; the ratio of acetic acid to acetate results from the desired pH. The indicated pH value is measured both in the pure buffer solution and in the finished injection or infusion solution.
• An embodiment according to the invention of a parenteral preparation of Bill 890 or one of its physiologically acceptable salts, such as e.g. the hydrochloride, contains the active ingredient in dosages of 1 mg / kg body weight to 30 mg / kg body weight daily, preferably in the range 3-15 mg / kg body weight.
• the application is preferably via continuous infusion over 24 hours, or optionally over several days, to maintain a steady state plasma level.
• Preferred is a concentration of 0.03% (w / v) to 0.2% (w / v); particularly preferred is a concentration of 0.03% (w / v) to 0.07% (w / v).
• the administered amount of the drug can be controlled.
• the application of 250 ml of a solution according to Example 3 corresponds to a dose of 175 mg Bill 890 daily.
• Example 4 Infusion solution 700 mq / 250 mL ("0.01 molar" acetate buffer pH 4)
• Example 6 Infusion solution 200 mg / 100 ml ("0.01 molar" acetate buffer pH 4)

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Engineering & Computer Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Epidemiology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Cardiology (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Heart & Thoracic Surgery (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Neurosurgery (AREA)
• Biochemistry (AREA)
• Vascular Medicine (AREA)
• Pain & Pain Management (AREA)
• Molecular Biology (AREA)
• Emergency Medicine (AREA)
• Dermatology (AREA)
• Urology & Nephrology (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Other In-Based Heterocyclic Compounds (AREA)

Priority Applications (4)

Applications Claiming Priority (2)

Publications (1)

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ID=29432394

Family Applications (1)

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• 2002
  • 2002-05-29 DE DE10223784A patent/DE10223784A1/de not_active Withdrawn
• 2003
  • 2003-05-23 CA CA002487153A patent/CA2487153A1/en not_active Abandoned
  • 2003-05-23 AU AU2003240699A patent/AU2003240699A1/en not_active Abandoned
  • 2003-05-23 JP JP2004506804A patent/JP2005531573A/ja active Pending
  • 2003-05-23 WO PCT/EP2003/005400 patent/WO2003099280A1/de not_active Application Discontinuation
  • 2003-05-23 EP EP03730101A patent/EP1511487A1/de not_active Withdrawn
  • 2003-05-27 UY UY27824A patent/UY27824A1/es not_active Application Discontinuation
  • 2003-05-27 TW TW092114284A patent/TW200406205A/zh unknown
  • 2003-05-27 PE PE2003000512A patent/PE20040067A1/es not_active Application Discontinuation
  • 2003-05-28 AR ARP030101864A patent/AR040135A1/es not_active Suspension/Interruption

Non-Patent Citations (4)

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