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
• • 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
  • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
  • A61K31/415—1,2-Diazoles
• • 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
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • 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

Definitions

• NSAID NSAID
• Ibuprofen (2-(4-isobutylphenyl)propionic acid) is a well known and commonly employed NSAID.
• S-ibuprofen single enantiomer
• racemic ibuprofen see for example U.S. Patent 4,877,620.
• the sympathomimetic amines phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine are sympathomimetic agents (Decongestants) which are useful for the treatment of nasal congestion arising from cold, allergy, flu or sinus conditions. These agents function by constricting the smaller arterioles of the nasal passages producing a decongestant effect.
• compositions for use in the treatment of pain and inflammation and the relief of nasal congestion and sinus pressure symptoms in a mammalian organism, said composition comprising:
• This invention is also directed to a method of treating pain and inflammation and the relief of nasal congestion and sinus pressure in a mammalian organism in need of such treatment comprising administering to such organism: (i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and
• This invention is also directed to a method of treating pain and inflammation and the relief of nasal congestion and sinus pressure in a mammalian organism in need of such treatment comprising administering to such organism:
• compositions and methods of the present invention may be used to treat pain and inflammation, or pain alone or inflammation alone where only one is present, along with the treatment of nasal congestion and sinus pressure symptoms.
• Substantially free of (R)-ibuprofen should be taken to mean that the ratio of (S)-ibuprofen to (R)-ibuprofen is at least 90:10.
• Substantially free with respect to a sympathomimetic amine stereoisomer should be taken to mean that the ratio of that stereoisomer to all other stereoisomers of the sympathomimetic amine is at least 90:10.
• Salts of (S)-ibuprofen include salts with alkali metals, such as sodium or potassium, salts with alkaline earth metals, such as calcium, or salts with other metals such as magnesium, aluminum, iron, zinc, copper, nickel or cobalt.
• Salts of (S)-ibuprofen further include the amino acid salts, particularly the basic a ino acids such as lysine or arginine. Specifically included within the above composition is (S)-ibuprofen- (S)-lysine and (S)-ibuprofen-(R)-lysine.
• Salts of the sympathomimetic amine include, but are not limited to, the hydrochloride, sulfate or bitartrate.
• (S)-ibuprofen may be prepared following the procedures disclosed in U.S. Patent 4,877,620.
• Metal salts of ibuprofen may be obtained by contacting a hydroxide, or carbonate with ibuprofen.
• Amino acid salts of ibuprofen may be obtained by contacting an amino acid in solution with ibuprofen.
• (S)-ibuprofen in an analgesic/decongestant combination offers significant advantages over the combination of racemic ibuprofen with a decongestant.
• (S)-ibuprofen provides a faster onset of pain relief and an enhanced degree of relief compared to racemic ibuprofen. These benefits are increased in an (S)-ibuprofen/decongestant combination as the decongestant may potentiate the action of (S)-ibuprofen. This has not heretofore been observed because the art has not proposed the combination of the (S)-ibuprofen enantiomer, absent (R)-ibuprofen, with a decongestant.
• the decongestant also may potentiate the duration of the analgesic and anti-inflammatory response.
• the presence of the (R)-ibuprofen may blur the potentiated effect.
• the absence of (R)-ibuprofen provides significant benefits particularly to the subject in the weakened state of a cold, flu, or allergy condition.
• the allergic contraindications sometimes associated with ibuprofen administration, and which may be particularly detrimental to the cold/allergy/flu sufferer, may be absent or reduced in a composition wherein the (R)-ibuprofen is absent.
• (R)-enantiomer or the removal of this enantiomer.
• the absence of inversion reduces or eliminates the formation and incorporation into fatty tissue of hybrid-ibuprofen containing trigylcerides.
• the renal burden and renal toxicities sometimes associated with ibuprofen therapy are reduced or absent in a substantially (R)-ibuprofen free composition.
• the absence of inactive enantiomers, particularly (R)-ibuprofen provides for significant size and weight advantages in a combination dosage form, particularly a sustained release dosage form.
• a sustained release dosage of ibuprofen may have required 800 to 1000 mg
• the employment of (S)-ibuprofen reduces the weight to 650 to 800 mg and provides for a more practical size tablet for an ibuprofen/decongestant combination.
• the absence of the inactive substances in the present composition may avoid undesirable toxic interactions and clearly avoids the metabolism necessary to remove the nonactive entity.
• An effective amount of (S)-ibuprofen, or a salt thereof, for use in an unit dose composition of this invention may range from 50 to 800 mg (S)-ibu- profen.
• the preferred amount of (S)-ibuprofen is about 100 to 400 mg.
• the amount of a salt such as (S)-ibuprofen-(S)-lysine is determined based on the amount of (S)-ibuprofen contained therein.
• the sympathomimetic amine (Decongestant) employed herein is selected from phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a pharmaceutically acceptable salt. Included within this invention are any diastereomers and/or enantio ers of each decongestant. Where a particular therapeutically active stereoisomer is not commercially available it may be prepared following standard resolution chemistry from the available racemic mixture.
• the amount of the decongestant useful in the practice of the present invention may vary from about 1 mg to 100 mg depending on the specific decongestant.
• the amount of a salt, such as pseudoephedrine hydrochloride, is determined based on the amount of active decongestant, such as pseudoephedrine, contained therein.
• compositions may be administered in the form of tablets, capsules, elixirs, syrups drops, granules, liquids, nasal spray inhaler, or a suspension.
• active components may be admixed with a pharmaceutically acceptable diluent such as lactose, starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol and in a liquid composition, ethyl alcohol.
• Acceptable binders such as PVP, starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as acacia, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes, may also be admixed with the active components.
• lubricants such as magnesium stearic acid talc, and disintegrators such as starch, methylcellulose, agar, bentonite and guar gum and super disintegrators such as docusate sodium, sodium starch glycollate or cross linked PVP may also be included.
• the active components may also be formulated in sustained release formulations. These formulations may be employed in oral, dermal, rectal or vaginal administrations. Such sustained release forms also include layered formulations which provide for distinct release ratio and thus may be more beneficial in allowing for short and long term relief.

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• Health & Medical Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Epidemiology (AREA)
• Pain & Pain Management (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Heart & Thoracic Surgery (AREA)
• Cardiology (AREA)
• Rheumatology (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Neurosurgery (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Applications Claiming Priority (4)

Publications (2)

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• 1992
  • 1992-03-24 WO PCT/US1992/002388 patent/WO1992017171A1/en not_active Application Discontinuation
  • 1992-03-24 JP JP4509691A patent/JPH06506684A/ja active Pending
  • 1992-03-24 CA CA002107331A patent/CA2107331A1/en not_active Abandoned
  • 1992-03-24 EP EP92910669A patent/EP0577757A1/de not_active Withdrawn
  • 1992-03-24 AU AU17662/92A patent/AU1766292A/en not_active Abandoned

Patent Citations (4)

Non-Patent Citations (1)

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