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EP1221949A2 - Procede et composition pour la prophylaxie et le traitement des symptomes lies aux affections de type rhume et d'allure grippale - Google Patents

Procede et composition pour la prophylaxie et le traitement des symptomes lies aux affections de type rhume et d'allure grippale

Info

Publication number
EP1221949A2
EP1221949A2 EP00948987A EP00948987A EP1221949A2 EP 1221949 A2 EP1221949 A2 EP 1221949A2 EP 00948987 A EP00948987 A EP 00948987A EP 00948987 A EP00948987 A EP 00948987A EP 1221949 A2 EP1221949 A2 EP 1221949A2
Authority
EP
European Patent Office
Prior art keywords
composition
stilbenic
phytoalexin
treatment
cold
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP00948987A
Other languages
German (de)
English (en)
Inventor
Nicholas Seymour Gantenberg
Robert Ernest Singer, Jr.
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Procter and Gamble Co
Original Assignee
Procter and Gamble Co
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 Procter and Gamble Co filed Critical Procter and Gamble Co
Publication of EP1221949A2 publication Critical patent/EP1221949A2/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses

Definitions

  • the present invention relates to a novel therapeutic use of stilbenic phytoalexins. More specifically, the embodiments of the present invention relate to the prophylaxis and treatment of symptoms associated with cold and influenza-like illnesses and the prophylaxis and treatment of congestion associated with respiratory afflictions.
  • BACKGROUND It is known that many different viruses and viral strains induce symptoms associated with respiratory viral infections. For example, the common cold and flu are caused by members of several families of viruses including influenza, parainfluenza viruses, rhinoviruses, respiratory syncytial viruses, enteroviruses, and coronaviruses. Pinpointing the specific cause of the illness is difficult and not practical since there are also a number of predisposing factors whose contribution to the manifestation of symptoms is not fully understood. Such factors include, but are not limited to, physical fatigue, psychological stress, and overall physical healthiness.
  • cough/cold products typically contain one or more of the following actives: nasal decongestants such as pseudoephedrine, oxymetazoline, antihistamines such as doxylamine, antitussives such as dextromethorphan, expectorants such as guaifenesin and antipyretics such as acetaminophen.
  • nasal decongestants such as pseudoephedrine, oxymetazoline
  • antihistamines such as doxylamine
  • antitussives such as dextromethorphan
  • expectorants such as guaifenesin
  • antipyretics such as acetaminophen.
  • Examples of these therapies include the use of interferon- ⁇ 2 , see Douglas et al., Prophylactic Efficacy of Intranasal Alpha?- Interferon against Rhinovirus Infection in the Family Setting, The New England Journal of Medicine, 314, pp. 65-70, 1986; bradykinin antagonist, see Higgins et al., A Study of the Efficacy of the Brandykinin Antagonist, NPC567, in Rhinovirus Infections in Human Volunteers, Antiviral Research vol. 14, pp.
  • glucocorticoid see Farr et al., A Randomized Controlled Trial of Glucocorticoid Prophylaxis against Experimental Rhinovirus Infection, The Journal of Infectious Diseases vol. 162, pp. 1173-1177, 1990; nedocromil, see Barrow et al., The Effect of Intranasal Nedocromil Sodium on Viral Upper Respiratory Tract Infections in Human Volunteers, Clinical and Experimental Allergy vol. 20, pp.
  • a number of patents have also been issued disclosing compositions for the treatment of the common cold and flu symptoms and their methods of use.
  • a sample of such patents include: U.S. Patents 5,240,694; 5,422,097, and 5,492,689, all to Gwaltney, disclosing treatment using combinations of antiviral and antiinflammatory compounds; U.S. Patents RE033.465 and 5,409,905, both to Eby disclosing treatment using zinc salts; and U.S. Patents 4,619,934 and 4,552,899, both to Sunshine, disclosing treatment of cough and colds using compositions comprising non-steroidal antiinflammatory drugs such as NSAIDS with antihistaminically effective materials such as chlorpheniramine.
  • compositions and preventative treatments known in the art, there remains a need to provide a consistent, effective, and safe method for the prophylaxis and treatment of cold and influenza-like symptoms as well as treatment of congestion associated with respiratory afflictions.
  • Applicants have discovered new means for the prophylaxis and treatment of cold and influenza-like symptoms as well as treatment of congestion associated with respiratory afflictions via administration of certain stilbenic phytoalexins.
  • Phytoalexins are defense substances with antimicrobial properties which are produced by plants after infections. They include various groups of natural substances (e.g., isoflavonoids, terpenoids, polyacetylenes and dihydrophenanthrenes). Different sources of phytoalexin include the roots of Veratrum grandiflorum, the bark of Pinus sibirica, Vitis vinifera, and Arachis hypogaea. Other sources include Eucalyptus, Polygonum and Nothofagus species and Cudrania javanensis. Phytoalexins can also exist naturally as an oligomer.
  • compositions comprising stilbenic phytoalexins can be prepared either utilizing natural occurring sources of stilbenic phytoalexins or synthesizing stilbenic phytoalexins.
  • One type of stilbenic phytoalexin that can be found in a variety of naturally occurring sources is 3,4',5-trihydroxystilbene resveratrol.
  • Reservatrols are found in relatively large amounts in red grapes and red wine and implicated for favorable pharmacological effects that include the prevention and therapy of atherosclerosis.
  • Research conducted on the components present in red wine that exert pharmacological effects indicates 3,4',5-trihydroxystilbene resveratrol's protective effects at the cardiovascular level. See, for example, Frankel E.
  • the present invention is directed to methods for the prophylaxis and treatment of cold and influenza-like symptoms and/or treatment of congestion associated with respiratory afflictions comprising administering to a subject a composition having a stilbenic phytoalexin having the structure:
  • R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from hydrogen and hydroxy.
  • the present invention is further directed to compositions including the above stilbenic phytoalexin.
  • safe and effective amount means an amount of active high enough to provide a significant positive modification of the condition to be treated, but low enough to avoid serious side effects (at a reasonable benefit/risk ratio), within the scope of sound medical judgment.
  • a safe and effective amount of active will vary with the particular condition being treated, the age and physical condition of the subject being treated, the severity of the condition the duration of the treatment, the nature of concurrent therapy and like factors.
  • Non-limiting symptoms associated with cold and influenza-like illnesses include nasal congestion, sneezing, sinus pain, sore throat, runny nose, cough, chest pain and headaches.
  • congestion is associated with certain respiratory afflictions. These respiratory afflictions include viral, bacterial, and fungal infections which may lead to sinusitis, otitis media, and pneumonia. Other respiratory afflictions that result in congestion include inflammatory and immunological responses to allergens and pollutants. Nasal congestion is one manifestation of congestion generally.
  • Congestion is characterized by localized edema at tissues or organs that are inflamed or injured in response to colds and respiratory ailments. To this end, congestion is accompanied by increased fluid production at mucus producing tissues such as the nose, lungs, and throat. The increased fluid production is responsible for reducing airflow through a lumenal site such as nasal passages or even the lungs. Other locations that become congested include the head or facial sinuses, ear canals, and the throat. Sinus and otic openings (ostia) are usually kept open by normal cellular processing of mucus, foreign particles and bacterial imbalances. However, these locations and openings can become clogged due to excessive edema which results in sinus, middle ear or head pain.
  • nasal congestion results in the sensation of one's nose and nasal passages being blocked with the inability to conduct airflow through the nares.
  • NAR nasal airway resistance
  • nares a physical measure of resistance to air flow, calculated from pressure gradients, through the nasal passage (e.g. nares, turbinates) under normal breathing patterns. Congestion in nasal tissues increases NAR. Increases in NAR coincide with the sensation of blocked and/or clogged airways. The biological mechanisms in nasal congestion are relevant to both symptoms associated with cold and influenza-like illnesses and congestion associated with respiratory afflictions. NAR is measured by acoustic and passive rhinometry. Amis, T.C., Oral airway flow dynamics in healthy humans, 515 J. Physiol. Lond. 293-8, 1999; Baroody, F.M.
  • stilbenic phytoalexins of Formula 1 are useful in the prophylaxis and treatment of symptoms associated with cold and influenza like illnesses as well as congestion associated with respiratory afflictions.
  • administering a safe and effective amount of a stilbenic phytoalexin of the present invention to a subject already suffering from nasal congestion decreases NAR by; preferably about 70% to about 98%; more preferably about 80% to about 95%; even more preferably about 85% to about 94%.
  • administering a safe and effective amount of a stilbenic phytoalexin of the present invention to a subject prior to suffering from nasal congestion minimizes increases in NAR by; preferably about 70% to about 98%; more preferably about 80% to about 95%; even more preferably about 85% to about 94%.
  • An embodiment of the present invention relates to a method for the prophylaxis and treatment of cold and influenza-like symptoms including administering to a subject a composition including a stilbenic phytoalexin having the following chemical Formula 1 :
  • R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently hydrogen or hydroxyl; and medicinally acceptable salts or esters thereof.
  • R represents mixtures of hydrogen and hydroxyl
  • the stilbenic phytoalexin is a tetrahydroxystilbene or trihydroxystilbene; more preferably still, 3,4', 5 - trihydroxystilbene resveratrol (hereinafter "resveratrol”), i.e., where R 1 , R 3 , R 5 , and are hydroxyl and R 2 , R 4 , and R 6 are hydrogen.
  • compositions useful in the methods of the present invention are discussed in more detail, below.
  • An embodiment of the present invention relates to compositions having a stilbenic phytoalexin of Formula 1.
  • compositions useful in the present invention include from about 0.01 % to about 99.99% of the stilbenic phytoalexin of Formula 1 ; more preferably from about 0.05% to about 30%; and more preferably still from about 0.1% to about 25%. 1.
  • a preferred embodiment of the present invention relates to compositions including a stilbenic phytoalexin of Formula 1 , above, in combination with a pharmaceutical agent.
  • pharmaceutical agents useful in the present invention include: Antihistamines, including, Hydroxyzine, Pyrilamine, Phenindamine,
  • Antitussives including, Hydrocodone, Noscapine, Benzonatate, Diphenhydramine, Chlophedianol, Clobutinol, Fominoben, Glaucine, Pholcodine, Zipeprol, Hydromorphone, Carbetapentane, Caramiphen, Levopropoxyphene, Codeine, Dextromethorphan, and mixtures thereof.
  • Antiinflammatories preferably Non-Steroidal Anti-inflammatories
  • NSAIDS including, Ketoprofen, Indoprofen, Indomethacin, Sulindac, Diflunisal, Ketorolac, Piroxicam, Meclofenamate, Benzydamine, Carprofen, Diclofenac, Etodolac, Fenbufen, Fenoprofen, Flurbiprofen, Mefenamic, Nabumetone, Phenylbutazone, Pirprofen, Tolmetin, Ibuprofen, Naproxen, Sodium naproxen, Aspirin, and mixtures thereof.
  • Analgesics including, Acetaminophen.
  • Expectorants/Mucolvtics including, Ambroxol, Bromhexine, Terpin,
  • Guaifenesin Potassium iodide, N-Acetyicysteine, and mixtures thereof.
  • Mast Cell Stabilizers preferably intranasally, or orally administered mast cell stabilizers, including, Cromolyn, Oxatamide, Ketotifen, Lodoxamide, Nedocromil, and mixtures thereof.
  • Leukotriene Antagonists including, Zileuton and others.
  • Methylxanthines including, Caffeine, Theophylline, Enprofylline, Pentoxifylline, Aminophylline, Dyphylline, and mixtures thereof.
  • Antioxidants or radical inhibitors including ⁇ Ascorbic acid, Tocopherol, Pycnogenol, and mixtures thereof.
  • Steroids preferably intranasally administered steroids, including,
  • Beclomethasone Fluticasone, Budesonide, Mometasone, Triamcinolone, Dexamethasone, Flunisolide, Prednisone, Hydrocortisone and mixtures thereof.
  • Bronchodilators preferably for inhalation, including, Albuterol, Epinephrine, Ephedrine, Metaproterenol, Terbutaline, Isoetharine, Terbutaline, Isoetharine, Pirbuterol, Bitolterol, Fenoterol, Rimeterol, Ipratroprium, and mixtures thereof.
  • Antivirals including, Amantadine, Rimantadine, Enviroxime, Nonoxinols, Acyclovir, Alpha-lnterferon, Beta-lnterferon, and mixtures thereof.
  • Biologies including, cytokine and celladhesion molecule inhibitors, ICAM antagonists, interleukin agonists or antagonists, hormones, polypeptides, amino acids, nucleotides, antibodies, and mixtures thereof.
  • the acid or base addition salts, esters, metabolites, stereoisomers and enantiomers of these actives are also contemplated as pharmaceutical agents useful in certain embodiments of the present invention, as well as the analogues of these actives that are safe and effective. It is also recognized that a pharmaceutical agent may be useful for more than one of the above uses, and these uses are clearly contemplated as well. This overlap is recognized in the art and adjusting dosages and the like to fit the indication is well within the purview of the skilled medical practitioner.
  • the composition further includes an enhancing agent.
  • Enhancing agents useful in the present invention include, but not limited to, herbs, phenols, polyphenols, anthocyamins, anthocyanosides, carotenoids, bioflavinoids, vitamins, metal ions, mineral salts, proanthocyanidins, antioxidants, and/or vegetal fibers.
  • Non-limiting examples include echinacea, tea polyphenols, epigallocatechin, beta carotene, grape seed extracts, lycopenes, flavones, quercetin, tocopherol, zinc, selenium, stannous, ascorbic acid, calcium, N-acetyl cysteine, and mixtures thereof.
  • the stilbenic phytoalexin of Formula 1 may originate from natural and/or synthetic sources. Orsini-F, et al., Isolation, synthesis, and antiplatelet aggregation activity of resveratrol 3-O-beta-D-glucopyranoside and related compounds, 60(11) J. Nat. Prod. 1082-7, 1997: Orsini-F, et. al.. Synthesis of biologically active polyphenolic glycosides (combretastatin and resveratrol series), 301(3-4) Carbohydr. Res. 95-109, 1997: Hain, et. al., Expression of a stilbene synthase gene in Nicotiana tabacum results in synthesis of the phytoalexin resveratrol, 15(2) Plant. Mol. Biol. 325-35, 1990 are cited as references incorporated herein.
  • the composition includes natural source products, natural source extracts, or natural source powders of the stilbenic phytoalexins of Formula 1.
  • natural source products include wine, grapes, Huzhang, and Polygonum cuspidatum.
  • compositions useful in the present invention may be a solid, semi- solid, liquid, semi-liquid; in the form of powders, granules, liposomes, tablets, capsules, gels, lozenges, dentifrice, and mouthwash.
  • the compositions useful in the present invention may be incorporated into microspheres, microcapsules, nanoparticles, liposomes and the like for controlled release.
  • the compositions may, in addition, conveniently comprise suspending, solubilizing, stabilizing, pH-adjusting agents and/or dispersing agents.
  • the composition is in the form of a herbal medicament.
  • Herbal medicament forms useful in the present invention include, but are not limited to, teas, decoctions, beverages, candies or other confection, foods, enteral liquid nutritional products, mouthwashes, lozenges, dentifrices, and dietary or nutritional supplements.
  • the administrative route of the compositions of the present invention includes any suitable route which leads to a concentration in the blood that provides a prophylactic and treatment benefit.
  • Suitable administration routes include, but are not necessarily limited to: oral, oral topical, parenteral, cutaneous, nasal, rectal, vaginal, ocular, inhalant, or combinations thereof.
  • the administrative route is oral or nasal.
  • Examples 1 and 2 Examples of toothpaste and tooth gel compositions of the subject invention are made by conventional processes by mixing the following:
  • mouthwash compositions of the subject in conventional processes by mixing the following:
  • Example 5 An example of a dental solution of the subject invention is made by mixing the following: Ingredients (Wt. %)
  • Example 6 An example of an oral gel composition of the subject invention is made by mixing the following:
  • An example of an intranasal spray solution is made by mixing the following: Ingredient Grams
  • Nonionic detergent 1 0.70
  • Flavoring used at a level in order to provide a pleasing taste.
  • An example of an intranasal drop solution is made by mixing the following:
  • Example 9 An example of an intranasal powder is made by mixing the following:
  • Lactose powder QS to 100 grams.
  • Example 10 An example of an inhalant is made by mixing the following: Inqredients Grams
  • Example 11 An example of sublingual tablet made by mixing the following: Ingredients Grams
  • Example 12 An example of sublingual tablet made by mixing the following:
  • Example 13 An example of a liquid composition administered to the sublingual mucosae or in the buccal cavity.
  • compositions of the present invention are further believed to improve the general maintenance and wellness of respiratory health.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Virology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Otolaryngology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention concerne des procédés pour la prophylaxie et le traitement des symptômes liés aux affections de type rhume et d'allure grippale et/ou la prophylaxie et le traitement de la congestion associée aux affections respiratoires. Les procédés en question consistent à administrer une composition renfermant une phytoalexine à base de stilbène. L'invention concerne également certaines compositions renfermant ladite phytoalexine, qui sont utiles pour les procédés décrits.
EP00948987A 1999-07-30 2000-07-28 Procede et composition pour la prophylaxie et le traitement des symptomes lies aux affections de type rhume et d'allure grippale Withdrawn EP1221949A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US36494499A 1999-07-30 1999-07-30
US364944 1999-07-30
PCT/US2000/020658 WO2001008671A2 (fr) 1999-07-30 2000-07-28 Procede et composition pour la prophylaxie et le traitement des symptomes lies aux affections de type rhume et d'allure grippale

Publications (1)

Publication Number Publication Date
EP1221949A2 true EP1221949A2 (fr) 2002-07-17

Family

ID=23436803

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00948987A Withdrawn EP1221949A2 (fr) 1999-07-30 2000-07-28 Procede et composition pour la prophylaxie et le traitement des symptomes lies aux affections de type rhume et d'allure grippale

Country Status (10)

Country Link
EP (1) EP1221949A2 (fr)
JP (1) JP2003505500A (fr)
CN (1) CN1377262A (fr)
AU (1) AU6240200A (fr)
CA (1) CA2379703A1 (fr)
CO (1) CO5200850A1 (fr)
HK (1) HK1049104A1 (fr)
PE (1) PE20010540A1 (fr)
TR (1) TR200200246T2 (fr)
WO (1) WO2001008671A2 (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6878751B1 (en) * 2000-10-19 2005-04-12 Imperial College Of Science Technology And Medicine Administration of resveratrol to treat inflammatory respiratory disorders
ITRM20020562A1 (it) 2002-11-06 2004-05-07 Sigma Tau Ind Farmaceuti Uso del resveratrolo per la preparazione di un medicamento utile per il trattamento delle infezioni da virus dell'influenza.
EP1845957B1 (fr) * 2005-02-04 2010-12-22 Peter Heger Procede pour produire un extrait medicamenteux contenant des hydroxystilbenes
DE602006013787D1 (de) * 2006-03-28 2010-06-02 Epitech Group Srl Eine Pharmazeutische Zusammensetzung zur Behandlung von Pathologien, die durch die allgemeine Immunantwort verursacht werden
CN100453071C (zh) * 2006-11-03 2009-01-21 李万忠 白藜芦醇口服多相脂质体及其制备方法
WO2008136173A1 (fr) * 2007-04-20 2008-11-13 Ochanomizu University Inhibiteur de la différenciation des adipocytes contenant un dérivé de stilbène en tant que principe actif
EP2231847B1 (fr) 2008-01-08 2018-10-31 David Rubin Procédé et compositions de conservation du vin
FR2933871B1 (fr) * 2008-07-18 2012-12-14 Yvery Formulation destinee a ameliorer la biodisponibilite d'une molecule hydrophobe
PL2544705T3 (pl) * 2010-03-12 2017-02-28 Synairgen Research Limited Interferon beta do zastosowania w leczeniu schorzenia dolnych dróg oddechowych powodowanego przez grypę
JP5848042B2 (ja) 2011-06-29 2016-01-27 株式会社ロッテ 眼疲労抑制組成物及びそれを含む飲食品
WO2013056298A1 (fr) * 2011-10-19 2013-04-25 Nad Life Pty Ltd Compositions pharmaceutiques de resvératrol
CN106581028A (zh) * 2016-11-30 2017-04-26 南宁市浩特竹鼠养殖场 一种治疗竹鼠感冒的西药及其制备方法
EP4132484A1 (fr) * 2020-04-10 2023-02-15 Galenus G.H. AG Composition comprenant du resvératrol

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JPH0753359A (ja) * 1993-06-11 1995-02-28 Kao Corp リポキシゲナーゼ阻害剤
FR2778337B1 (fr) * 1998-05-05 2001-08-31 Inst Nat Sante Rech Med Antagonistes des ligands du recepteur des arylhydrocarbures
AU4084599A (en) * 1998-05-18 1999-12-06 Oklahoma Medical Research Foundation Resveratrol inhibition of myeloperoxidase
US6197834B1 (en) * 1998-09-01 2001-03-06 Northeastern Ohio Universities College Of Medicine Method of inhibiting formation of infectious herpes virus particles
ES2258337T3 (es) * 1998-09-08 2006-08-16 Cornell Research Foundation, Inc. Uso de inhibidores de la ciclooxigenasa-2 para el tratamiento de enfermedades inflamatorias de cabeza y cuello.

Non-Patent Citations (1)

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Title
See references of WO0108671A2 *

Also Published As

Publication number Publication date
AU6240200A (en) 2001-02-19
CN1377262A (zh) 2002-10-30
PE20010540A1 (es) 2001-05-15
JP2003505500A (ja) 2003-02-12
WO2001008671A3 (fr) 2002-05-02
CA2379703A1 (fr) 2001-02-08
WO2001008671A2 (fr) 2001-02-08
HK1049104A1 (zh) 2003-05-02
TR200200246T2 (tr) 2002-09-23
CO5200850A1 (es) 2002-09-27

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