WO1992017171A1 - Ibuprofen-decongestant combinations - Google Patents

Ibuprofen-decongestant combinations Download PDF

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Publication number
WO1992017171A1
WO1992017171A1 PCT/US1992/002388 US9202388W WO9217171A1 WO 1992017171 A1 WO1992017171 A1 WO 1992017171A1 US 9202388 W US9202388 W US 9202388W WO 9217171 A1 WO9217171 A1 WO 9217171A1
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Prior art keywords
ibuprofen
substantially free
salt
effective amount
phenylpropanolamine
Prior art date
Application number
PCT/US1992/002388
Other languages
French (fr)
Inventor
Robert T. Sims
William Slivka
Original Assignee
Merck & Co., Inc.
Mcneil-Ppc, Inc.
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Filing date
Publication date
Application filed by Merck & Co., Inc., Mcneil-Ppc, Inc. filed Critical Merck & Co., Inc.
Priority to JP4509691A priority Critical patent/JPH06506684A/en
Publication of WO1992017171A1 publication Critical patent/WO1992017171A1/en

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    • 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)

Abstract

This invention relates to pharmaceutical compositions for use in the treatment of pain and inflammation and the relief of nasal congestion and sinus pressure in a mammalian organism, said composition comprising: (i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and (ii) a sympathomimetically effective amount of at least one of the sympathomimetic amines selected from phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers or a pharmaceutically acceptable salt thereof.

Description

TITLE OF THE INVENTION IBUPROFEN-DECONGESTANT COMBINATIONS
BACKGROUND OF THE INVENTION The non-steroidal anti-inflammatory drugs
(NSAID) have been utilized in the treatment of pain/ inflammation and have been disclosed as useful in the treatment, management and mitigation of cold symptoms and the pain associated therewith. Ibuprofen (2-(4-isobutylphenyl)propionic acid) is a well known and commonly employed NSAID. Recently, it has been found that a faster onset of pain relief and an enhanced analgesic response can be obtained by the utilization of the single enantiomer (S)-ibuprofen in comparison to 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.
Combinations of ibuprofen with decongestants have been disclosed, however despite the fact that the cold/pain sufferer is in need of quick and enhanced relief there has been no consideration given to the employment of (S)-ibuprofen, or a salt thereof, in combination with a decongestant for the treatment of pain and the relief of allergy, cold symptoms.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to pharmaceutical 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:
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and
(ii) a sympathomimetically effective amount of at least one of the sympathomimetic amines phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active stereoisomer thereof substantially free of its other εtereoisomers or a pharmaceutically acceptable salt thereof. 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
(ii) a sympathomimetically effective amount of at least one of the sympathomimetic amines phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers or a pharmaceutically acceptable salt thereof.
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
(ii) a sympathomimetically effective amount of at least one of the sympathomimetic amines phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers or a pharmaceutically acceptable salt thereof. The 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.
The utilization of (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. Furthermore 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. Furthermore, 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.
The subject using the (S)-ibuprofen/decon¬ gestant combination will no longer need to divert metabolic energy to the inversion of the
(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. Where 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. Where only a single stereoisomer of the decongestant is active (therapeutically active stereoisomer), 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.
The present compositions may be administered in the form of tablets, capsules, elixirs, syrups drops, granules, liquids, nasal spray inhaler, or a suspension. For oral administration the 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. Where necessary 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.
The following examples illustrate the compositions of the present invention and as such are not to be considered as limiting the invention set forth in the claims appended hereto.
EXAMPLE 1
(S)-ibuprofen-(S)-lvsine. Decongestant Tablet
(S)-ibuprofen-(S)-lysine 342 mg
Pseudoephedrine HC1
PVP
Avicel PH101
Magnesium Stearate
Figure imgf000010_0001
(S)-ibuprofen-(S)-lvsine. Decongestant Sustained Release
(S)-ibuprofen-(S)-lysine 685 mg
Pseudoephedrine HC1 60 mg
PVP 30 mg
Avicel PH101 80 mg
Magnesium Stearate 8 mg Methocel E10MCR 66 mg
Methocel K100MLV 200 mg EXAMPLE 3
(S)-ibuprofen. Decongestant Sustained Release
(S)-ibuprofen Pseudoephedrine HC1 PVP
Avicel PH101 Magnesium Stearate Methocel E10MCR Methocel K100MLV
Figure imgf000011_0001
(S)-ibuprofen-(S)-lvsine/decongestant Solution
(S)-ibuprofen-(S)-lysine 342 mg Pseudoephedrine HC1 15 mg q.s. syrup 5 ml

Claims

WHAT IS CLAIMED IS:
1. A pharmaceutical composition for use in the treatment of pain and inflammation and the relief of nasal congestion and sinus pressure in a mammalian organism and adapted for unit dosage oral administration said composition comprising:
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and
(ii) a sympathomimetically effective amount of at least one of the sympathomimetic amines phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers or a pharmaceutically acceptable salt thereof.
2. A composition of Claim 1 where the ibuprofen is present as the salt (S)-ibuprofen- (S)-lysine, or (S)-ibuprofen-(R)-lysine.
3. A composition of Claim 1 comprising at least 50 mg of (S)-ibuprofen.
4. A composition of Claim 3 wherein the sympathomimetic amine is selected from: phenylephrine, phenylpropanolamine, pseudoephedrine, or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers, or a pharmaceutically acceptable salt.
5. A method of treating pain and inflammation and the relief of allergy and cold symptoms 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;
(ii) a sympathomimetically effective amount of at least one of the sympathomimetic amines phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers or a pharmaceutically acceptable salt thereof.
6. A method of eliciting an onset hastened and enhanced response for the treatment of pain and inflammation and the relief of allergy and cold symptoms in a mammaliam 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 (R)-ibuprofen; and (ii) a sympathomimetically effective amount of at least one of the sympathomimetic amines phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers or a pharmaceutically acceptable salt thereof.
7. A method of reducing the side effects associated with the administration of an ibuprofen/ decongestant combination which comprises the administration of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen, and at least one of the sympathomimetic amines, phenylephrine, phenylpropanolamine, pseudophedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers, or a pharmaceutically acceptable salt thereof.
8. A method of reducing the size and weight of an ibuprofen/decongestant combination dosage form which comprises combining (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen and at least one of the sympathomimetic amines, phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, xylometazoline, propylhexedrine, levo-desoxyephedrine or a therapeutically active steroisomer thereof substantially free of its other stereoisomers, or a pharmaceutically acceptable salt thereof.
PCT/US1992/002388 1991-04-01 1992-03-24 Ibuprofen-decongestant combinations WO1992017171A1 (en)

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JP4509691A JPH06506684A (en) 1991-04-01 1992-03-24 Ibuprofen - decongestant formulation

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US67877391A 1991-04-01 1991-04-01
US678,773 1991-04-01
US81252391A 1991-12-20 1991-12-20
US812,523 1991-12-20

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WO1994014476A1 (en) * 1992-12-21 1994-07-07 The Procter & Gamble Company Use of s(+) antipodes of analgesic agents for the manufacture of a composition to treat respiratory disorders
WO1995007103A1 (en) * 1993-09-07 1995-03-16 The Procter & Gamble Company Compositions containing an amino acid salt of propionic acid non-steroidal anti-inflammatory agent and at least one of a decongestant, an expectorant, an antihistamine and an antitussive
WO2000001379A1 (en) * 1998-07-01 2000-01-13 Warner-Lambert Company (-)-pseudoephedrine as a sympathomimetic drug
EP1059084A2 (en) * 1999-06-10 2000-12-13 McNEIL-PPC, INC. Rapidly absorbed liquid compositions containing an amine and a NSAID
WO2002019996A2 (en) * 2000-09-08 2002-03-14 Warner-Lambert Compan Llc Prevention of acute sinusitis and sinus attack
WO2005079272A3 (en) * 2004-02-17 2006-02-23 Wyeth Corp Compositions of non-steroidal anti-inflammatory drugs and decongestants or anti-histamines
US7863287B2 (en) 2002-12-18 2011-01-04 Wyeth Llc Compositions of non-steroidal anti-inflammatory drugs, decongestants and anti-histamines
US7973068B2 (en) * 1998-10-20 2011-07-05 Omeros Corporation Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation
AU2011244930B2 (en) * 1999-06-10 2012-08-30 Mcneil-Ppc, Inc. Rapidly absorbed liquid compositions
US9254271B2 (en) 1998-10-20 2016-02-09 Omeros Corporation Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation
AU2022201576A1 (en) * 2022-03-08 2023-09-28 Aft Pharmaceuticals Limited Medication

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WO1994014476A1 (en) * 1992-12-21 1994-07-07 The Procter & Gamble Company Use of s(+) antipodes of analgesic agents for the manufacture of a composition to treat respiratory disorders
WO1995007103A1 (en) * 1993-09-07 1995-03-16 The Procter & Gamble Company Compositions containing an amino acid salt of propionic acid non-steroidal anti-inflammatory agent and at least one of a decongestant, an expectorant, an antihistamine and an antitussive
US6495529B1 (en) 1998-07-01 2002-12-17 Warner-Lambert Company (−)-Pseudoephedrine as a sympathomimetic drug
WO2000001379A1 (en) * 1998-07-01 2000-01-13 Warner-Lambert Company (-)-pseudoephedrine as a sympathomimetic drug
AU772807B2 (en) * 1998-07-01 2004-05-06 Warner-Lambert Company Llc (-)-pseudoephedrine as a sympathomimetic drug
US7973068B2 (en) * 1998-10-20 2011-07-05 Omeros Corporation Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation
US8450309B2 (en) 1998-10-20 2013-05-28 Omeros Corporation Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation
US9254271B2 (en) 1998-10-20 2016-02-09 Omeros Corporation Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation
EP1059084A3 (en) * 1999-06-10 2002-11-06 McNEIL-PPC, INC. Rapidly absorbed liquid compositions containing an amine and a NSAID
US7060730B2 (en) 1999-06-10 2006-06-13 Cathy Klech Gelotte Rapidly absorbed liquid compositions
EP1059084A2 (en) * 1999-06-10 2000-12-13 McNEIL-PPC, INC. Rapidly absorbed liquid compositions containing an amine and a NSAID
AU2011244930B2 (en) * 1999-06-10 2012-08-30 Mcneil-Ppc, Inc. Rapidly absorbed liquid compositions
WO2002019996A3 (en) * 2000-09-08 2002-06-13 Warner Lambert Co Prevention of acute sinusitis and sinus attack
WO2002019996A2 (en) * 2000-09-08 2002-03-14 Warner-Lambert Compan Llc Prevention of acute sinusitis and sinus attack
US7863287B2 (en) 2002-12-18 2011-01-04 Wyeth Llc Compositions of non-steroidal anti-inflammatory drugs, decongestants and anti-histamines
WO2005079272A3 (en) * 2004-02-17 2006-02-23 Wyeth Corp Compositions of non-steroidal anti-inflammatory drugs and decongestants or anti-histamines
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AU1766292A (en) 1992-11-02
JPH06506684A (en) 1994-07-28
EP0577757A4 (en) 1994-02-23
CA2107331A1 (en) 1992-10-02
EP0577757A1 (en) 1994-01-12

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