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WO1992005783A1 - Combinaisons d'ibuprofene-antihistamine - Google Patents

Combinaisons d'ibuprofene-antihistamine Download PDF

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Publication number
WO1992005783A1
WO1992005783A1 PCT/US1991/007007 US9107007W WO9205783A1 WO 1992005783 A1 WO1992005783 A1 WO 1992005783A1 US 9107007 W US9107007 W US 9107007W WO 9205783 A1 WO9205783 A1 WO 9205783A1
Authority
WO
WIPO (PCT)
Prior art keywords
antihistamine
ibuprofen
substantially free
composition
stereoisomers
Prior art date
Application number
PCT/US1991/007007
Other languages
English (en)
Inventor
Thomas N. Gates
Robert T. Sims
King Chiu Kwan
William Slivka
Original Assignee
Merck & Co., Inc.
Mcneill-Ppc, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck & Co., Inc., Mcneill-Ppc, Inc. filed Critical Merck & Co., Inc.
Priority to JP3517917A priority Critical patent/JPH06502166A/ja
Publication of WO1992005783A1 publication Critical patent/WO1992005783A1/fr

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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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • 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
    • A61K31/275—Nitriles; Isonitriles
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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

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.
  • Antihistamines useful for the treatment of cold and flu symptoms, may be categorized into conventional and non-sedating antihistamines.
  • the conventional antihistamines exhibit an anticholinergic effect which may be advantageous to the cold/allergy sufferer.
  • the conventional antihistamine may also have an advantage for the subject who wishes to induce drowsiness.
  • Non-sedating antihistamines have significant benefits to the cold/allergy sufferer who needs to maintain alertness.
  • compositions for use in the treatment of pain and inflammation and the relief of allergy and cold symptoms in a mammalian organism comprising:
  • This invention is also directed to 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:
  • This invention is also directed to a method of eliciting an onset enhanced and enhanced response for the treatment of 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:
  • 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 an antihistamine stereoisomer should be taken to mean that the ratio of that stereoisomer to all other stereoisomers of the antihistamine 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 amino acids such as lysine or arginine. Specifically included within the above composition is (S)-ibuprofen- (S)-lysine and (S)-ibuprofen-(R)-lysine.
  • (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.
  • compositions of the present invention are useful in the treatment of pain and inflammation and the symptoms such as runny nose, sneezing, sniffles and itchy watering eyes that accompany allergies and colds.
  • (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/antihistamine combination as the antihistamine potentiates 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 an antihistamine. 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 or flu condition.
  • the allergic contraindications sometimes associated with ibuprofen administration, and which may be particularly detrimental to the cold/allergy sufferer, are absent or reduced in a composition wherein the (R)-ibuprofen is absent.
  • the subject 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 triglycerides .
  • 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 the inactive substances in the present composition avoids undesirable toxic interactions and clearly avoids the metabolism necessary to remove the nonactive entity.
  • the absence of inactive enantiomers, particularly (R)-ibuprofen provides for significant size and weight advantages in a 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/antihistamine combination.
  • EPO publication 348,683 discloses that the combination of a piperidinoalkanol, such as terfenadine, with ibuprofen results in_ a hardened mixture rather than a flowable powder. This was attributed to an incompatability between the substances and the mixture to further processing to form a pharmaceutical dosage having acceptable bioavailability characteristics.
  • the present invention in employing a salt of ibuprofen, particularly the lysine or arginine salt, overcomes the incompatability problem and results in a pharmaceutically acceptable dosage formulation.
  • 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 antihistamine employed herein is selected from the conventional and the non-sedating types.
  • the conventional antihistamines competitively antagonize those pharmacological effects of histamine which are mediated through activation of histamine H 2 -receptor sites on effector cells.
  • the conventional antihistamines also exhibit an anticholinergic (drying) effect.
  • the conventional antihistamine is selected from: chlorpheniramine, brompheniramine, dexchlorpheniramine, dexbrompheniramine, triprolidine, hydroxyzine, doxylamine, tripelennamine, cyproheptadine, carbinoxamine, bromodiphenhydramine, phenindiamine, pyrilamine, azatadine or diphenhydramine or a pharmaceutically acceptable salt
  • the non-sedating antihistamine is selected from: acrivastine, A ⁇ R-11325, astemizole, azelastine, cetirizine, ebastine, ketotifen, lodoxamide, loratidine, levocabastine, mequitazine, oxatomide, setastine, tazifylline, temelastine or terfenadine.
  • any diastereomers and/or enantiomers of each antihistamine are any diastereomers and/or enantiomers of each antihistamine. 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 antihistamine useful in the practice of the present invention may vary from about 1 mg to 100 mg depending on the specific antihistamine.
  • compositions may be administered in the form of tablets, capsules, elixirs, syrups 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.
  • 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.
  • 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)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention se rapporte à des compositions pharmaceutiques devant être utilisées pour le traitement de douleurs et d'inflammations et le soulagement de symptômes allergiques et grippaux dans un organisme mammifère, ladite composition comprenant: (i) une quantité de (S)-ibuprofène, ou d'un sel de celui-ci, pratiquement dépourvue de (R)-ibuprofène et produisant un effet analgésique et anti-inflammatoire; et (ii) une quantité d'au moins l'un des antihistamines ou d'un stéréo-isomère thérapeutiquement actif de celui-ci, pratiquement dépourvue de ses autres stéréo-isomères et produisant un effet anti-histaminique.
PCT/US1991/007007 1990-09-28 1991-09-25 Combinaisons d'ibuprofene-antihistamine WO1992005783A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP3517917A JPH06502166A (ja) 1990-09-28 1991-09-25 イブプロフェン−抗ヒスタミン薬の組み合わせ

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US58924590A 1990-09-28 1990-09-28
US58924190A 1990-09-28 1990-09-28
US589,241 1990-09-28
US589,245 1990-09-28

Publications (1)

Publication Number Publication Date
WO1992005783A1 true WO1992005783A1 (fr) 1992-04-16

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1991/007007 WO1992005783A1 (fr) 1990-09-28 1991-09-25 Combinaisons d'ibuprofene-antihistamine

Country Status (5)

Country Link
EP (1) EP0550668A4 (fr)
JP (1) JPH06502166A (fr)
AU (1) AU8764191A (fr)
CA (1) CA2092566A1 (fr)
WO (1) WO1992005783A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994014449A1 (fr) * 1992-12-21 1994-07-07 The Procter & Gamble Company Compositions contenant de la cafeine et s(+)-ibuprofene ou s(+)-flurbiprofene ou s(+)-cetoprofene
WO1995011677A1 (fr) * 1993-10-25 1995-05-04 Merrell Pharmaceuticals Inc. Composition pharmaceutique stable a base de terfenadine et d'ibuprofene
WO1995025518A1 (fr) * 1994-03-18 1995-09-28 Ciba-Geigy Ag Solution aqueuse de levocabastine a usage ophtalmique
WO1997004808A1 (fr) * 1995-07-28 1997-02-13 The Procter & Gamble Company Compositions contenant des analgesiques et des antihistaminiques et procedes de traitement d'affections respiratoires
EP0663819A4 (fr) * 1992-09-29 1998-05-27 Merck & Co Inc Association d'ibuprofene et de cafeine.
WO2009145921A1 (fr) * 2008-05-30 2009-12-03 Fairfield Clinical Trials, Llc Procédé et composition pour une inflammation et une décoloration de la peau
EP2240018A4 (fr) * 2008-01-04 2012-01-11 Schabar Res Associates Llc Méthodes de mesure de la réponse d'un patient à l'administration d'un médicament ou de ses compositions
EP2493465A4 (fr) * 2009-10-26 2012-09-05 Sephoris Pharmaceuticals Llc Traitement de coups de soleil utilisant des analgésiques et des antihistaminiques
WO2016154028A1 (fr) 2015-03-26 2016-09-29 Iversen Jacqueline M Procédés et compositions pour inhiber les symptômes associés à la veisalgie
US11324727B2 (en) 2020-07-15 2022-05-10 Schabar Research Associates, Llc Unit oral dose compositions composed of naproxen sodium and famotidine for the treatment of acute pain and the reduction of the severity of heartburn and/or the risk of heartburn
US11331307B2 (en) 2020-07-15 2022-05-17 Schabar Research Associates, Llc Unit oral dose compositions composed of ibuprofen and famotidine for the treatment of acute pain and the reduction of the severity and/or risk of heartburn
EP4226923A4 (fr) * 2020-12-04 2024-08-21 Laboratorios Silanes, S.A. de C.V. Composition pharmaceutique d'un analgésique et d'un antihistaminique pour le traitement de maladies respiratoires

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4614638B2 (ja) * 2002-06-07 2011-01-19 第一三共株式会社 鎮痛剤組成物
JP2010159299A (ja) * 2002-07-04 2010-07-22 Daiichi Sankyo Co Ltd ロキソプロフェンとケトチフェンを含有する解熱剤組成物
JP4614640B2 (ja) * 2002-07-04 2011-01-19 第一三共株式会社 解熱剤組成物

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US4783465A (en) * 1984-04-09 1988-11-08 Analgesic Associates Cough/cold mixtures comprising non-sedating antihistamine drugs
US4851444A (en) * 1987-07-10 1989-07-25 Analgesic Associates Onset-hastened/enhanced analgesia
US4877620A (en) * 1986-11-14 1989-10-31 MEDICE Chem.- Pharm. Fabrik Putter GmbH & Co. KG Ibuprofen-containing medicament
US4980375A (en) * 1987-07-10 1990-12-25 Sterling Drug Inc. Onset-hastened/enhanced antipyretic response

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4783465A (en) * 1984-04-09 1988-11-08 Analgesic Associates Cough/cold mixtures comprising non-sedating antihistamine drugs
US4877620A (en) * 1986-11-14 1989-10-31 MEDICE Chem.- Pharm. Fabrik Putter GmbH & Co. KG Ibuprofen-containing medicament
US4851444A (en) * 1987-07-10 1989-07-25 Analgesic Associates Onset-hastened/enhanced analgesia
US4980375A (en) * 1987-07-10 1990-12-25 Sterling Drug Inc. Onset-hastened/enhanced antipyretic response

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0663819A4 (fr) * 1992-09-29 1998-05-27 Merck & Co Inc Association d'ibuprofene et de cafeine.
AU672279B2 (en) * 1992-12-21 1996-09-26 Procter & Gamble Company, The Compositions containing caffeine and S(+)-ibuprofen or S(+)-flurbiprofen or S(+)-ketoprofen
WO1994014449A1 (fr) * 1992-12-21 1994-07-07 The Procter & Gamble Company Compositions contenant de la cafeine et s(+)-ibuprofene ou s(+)-flurbiprofene ou s(+)-cetoprofene
CN1060040C (zh) * 1993-10-25 2001-01-03 默里尔药物公司 稳定的丁苯哌丁醇与布洛芬的药物组合物
WO1995011677A1 (fr) * 1993-10-25 1995-05-04 Merrell Pharmaceuticals Inc. Composition pharmaceutique stable a base de terfenadine et d'ibuprofene
WO1995025518A1 (fr) * 1994-03-18 1995-09-28 Ciba-Geigy Ag Solution aqueuse de levocabastine a usage ophtalmique
WO1997004808A1 (fr) * 1995-07-28 1997-02-13 The Procter & Gamble Company Compositions contenant des analgesiques et des antihistaminiques et procedes de traitement d'affections respiratoires
EP2240018A4 (fr) * 2008-01-04 2012-01-11 Schabar Res Associates Llc Méthodes de mesure de la réponse d'un patient à l'administration d'un médicament ou de ses compositions
US9044465B2 (en) 2008-01-04 2015-06-02 Schabar Research Associates, Llc Use of analgesic potentiating compounds to potentiate the analgesic properties of an analgesic compound
US8771643B2 (en) 2008-01-04 2014-07-08 Schabar Research Associates Llc Use of analgesic potentiating compounds to potentiate the analgesic properties of an analgesic compound
AU2009204360B2 (en) * 2008-01-04 2014-12-18 Src, Inc. The use of analgesic potentiating compounds to potentiate the analgesic properties of an analgesic compound and single dose compositions thereof
WO2009145921A1 (fr) * 2008-05-30 2009-12-03 Fairfield Clinical Trials, Llc Procédé et composition pour une inflammation et une décoloration de la peau
WO2009158144A1 (fr) * 2008-05-30 2009-12-30 Fairfield Clinical Trials Llc Procédé et composition pour des dermatoses
EP2853262A1 (fr) * 2009-10-26 2015-04-01 Sephoris Pharmaceuticals, LLC Traitement de l'érythème solaire utilisant des analgésiques et des antihistaminiques
US10751331B2 (en) 2009-10-26 2020-08-25 Sephoris Pharmaceuticals, Llc Treatment of sunburn using analgesics and antihistamines
EP2493465A4 (fr) * 2009-10-26 2012-09-05 Sephoris Pharmaceuticals Llc Traitement de coups de soleil utilisant des analgésiques et des antihistaminiques
US8957095B2 (en) 2009-10-26 2015-02-17 Sephoris Pharmaceuticals, Llc Treatment of sunburn using analgesics and antihistamines
AU2010315561B2 (en) * 2009-10-26 2016-10-20 Sephoris Pharmaceuticals, Llc Treatment of sunburn using analgesics and antihistamines
US9895360B2 (en) 2009-10-26 2018-02-20 Sephoris Pharmaceuticals, Llc Treatment of sunburn using analgesics and antihistamines
CN107635549A (zh) * 2015-03-26 2018-01-26 杰奎琳·M·艾弗森 抑制与宿醉相关的症状的方法和组合物
WO2016154028A1 (fr) 2015-03-26 2016-09-29 Iversen Jacqueline M Procédés et compositions pour inhiber les symptômes associés à la veisalgie
AU2016235484B2 (en) * 2015-03-26 2021-02-18 Jacqueline M. Iversen Methods and compositions to inhibit symptoms associated with veisalgia
EP3273952B1 (fr) * 2015-03-26 2022-06-15 Sen-Jam Pharmaceutical LLC Combinaison du naproxen et fexofenadine pour inhiber les symptômes associés à la veisalgie
CN115887456A (zh) * 2015-03-26 2023-04-04 杰奎琳·M·艾弗森 抑制与宿醉相关的症状的方法和组合物
US11324727B2 (en) 2020-07-15 2022-05-10 Schabar Research Associates, Llc Unit oral dose compositions composed of naproxen sodium and famotidine for the treatment of acute pain and the reduction of the severity of heartburn and/or the risk of heartburn
US11331307B2 (en) 2020-07-15 2022-05-17 Schabar Research Associates, Llc Unit oral dose compositions composed of ibuprofen and famotidine for the treatment of acute pain and the reduction of the severity and/or risk of heartburn
US12048690B2 (en) 2020-07-15 2024-07-30 Schabar Research Associates Llc Unit oral dose compositions composed of naproxen sodium and famotidine for the treatment of acute pain and the reduction of the severity and/or risk of heartburn
US12053457B2 (en) 2020-07-15 2024-08-06 Schabar Research Associates Llc Unit oral dose compositions composed of ibuprofen and famotidine for the treatment of acute pain and the reduction of the severity and/or risk of heartburn
EP4226923A4 (fr) * 2020-12-04 2024-08-21 Laboratorios Silanes, S.A. de C.V. Composition pharmaceutique d'un analgésique et d'un antihistaminique pour le traitement de maladies respiratoires

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CA2092566A1 (fr) 1992-03-29
JPH06502166A (ja) 1994-03-10
AU8764191A (en) 1992-04-28
EP0550668A4 (en) 1993-10-13
EP0550668A1 (fr) 1993-07-14

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