[go: up one dir, main page]

EP1093365A2 - Compositions renfermant des analogues d'acide gamma-aminobutyrique (gaba) et un decongestionnant destinees a soulager des cephalees localisees dans les sinus - Google Patents

Compositions renfermant des analogues d'acide gamma-aminobutyrique (gaba) et un decongestionnant destinees a soulager des cephalees localisees dans les sinus

Info

Publication number
EP1093365A2
EP1093365A2 EP99928815A EP99928815A EP1093365A2 EP 1093365 A2 EP1093365 A2 EP 1093365A2 EP 99928815 A EP99928815 A EP 99928815A EP 99928815 A EP99928815 A EP 99928815A EP 1093365 A2 EP1093365 A2 EP 1093365A2
Authority
EP
European Patent Office
Prior art keywords
formula
decongestant
gabapentin
hydrogen
composition
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Withdrawn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
EP99928815A
Other languages
German (de)
English (en)
Inventor
Leslie Magnus
Catherine A. Segal
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.)
Warner Lambert Co LLC
Original Assignee
Warner Lambert Co LLC
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 Warner Lambert Co LLC filed Critical Warner Lambert Co LLC
Publication of EP1093365A2 publication Critical patent/EP1093365A2/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Withdrawn legal-status Critical Current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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • 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

  • the present invention relates to compositions comprising analogs of glutamic acid and gamma-aminobutyric acid (GABA) in combination with a decongestant for the treatment of sinus headache pain.
  • GABA gamma-aminobutyric acid
  • GABA analogs are known agents useful in antiseizure therapy for central nervous system disorders such as epilepsy, Huntington's chorea, cerebral ischemia, Parkinson's disease, tardive dyskinesia, and spasticity. It has also been suggested that the compounds can be used as antidepressants, anxiolytics, and antipsychotics. See WO 92/09560 (United States Serial Number 618,692 filed November 27, 1990) and WP 93/23383 (United States Serial Number 886,080 filed May 20, 1992).
  • WO 97/33858 teaches that compounds related to gabapentin are useful or treating epilespy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, and neuropathological disorders. WO 97/33858 does not specify what forms of pain are treated.
  • the compounds of the invention are known for treatment of neuropathic pain.
  • Ann Pharmacother 1997 Sep, 31:9, 1082-3; Zapp JJ., Postpoliomyelitis pain treated with gabapentin [letter].
  • Sinus headaches result from the inflammation of the sinus linings resulting in sinus pressure and pain. Sinus headaches are a common problem for adults over the age of 35 year and are often precipitated by the common cold or allergic rhinits. Common treatments include analgesics and decongestants.
  • This invention provides a method for treating sinus headache comprising administering to a subject suffering from sinus headache an effective amount of a GABA analog in combination with a decongestant.
  • a preferred GABA analog utilizes a cyclic amino acid compound of Formula I
  • Rj is hydrogen or lower alkyl and n is an integer of from 4 to 6, and the pharmaceutically acceptable salts thereof.
  • An especially preferred embodiment utilizes a compound of Formula I where R ⁇ is hydrogen and n is 4, which compound is l-(aminomethyl)-cyclohexane acetic acid, known genetically as gabapentin.
  • the decongestants useful in the present invention include various sympathomimetic drugs such as pseudoephedrine, ephedrine, phenylephrine and pharmaceutically acceptable salts thereof.
  • An additional decongestant useful in the present invention is the complementary medicine ma huong, which is known for its decongestant properties. These decongestants are known to those skilled in the art as therapeutic agents effective in the relief of nasal congestion.
  • the invention includes treating sinus headache or sinus pain with a compound of Formula II in combination with a decongestant.
  • Formula II is
  • R2 is a straight or branched alkyl of from 1 to 6 carbon atoms, phenyl, or cycloalkyl having from 3 to 6 carbon atoms;
  • Preferred compounds of the invention are those wherein R4 and R3 are hydrogen, and R2 is -(CH2) ⁇ -2 ⁇ i C4H9 as an (R), (S), or (R,S) isomer.
  • the more preferred compounds of Formula II invention are (S)-3- (aminomethyl)-5-methylhexanoic acid and 3-aminomethyl-5-methyl-hexanoic acid, now known generically as pregabalin.
  • the method of this invention utilizes any GABA analog.
  • a GABA analog is any compound derived from or based upon gamma-aminobutyric acid.
  • the compounds are readily available, either commercially, or by synthetic methodology well-known to those skilled in the art of organic chemistry.
  • the preferred GABA analogs to be utilized in the method of this invention are cyclic amino acids of Formula I. These are described in U.S. Patent 4,024,175, which is incorporated herein by reference.
  • Another preferred method utilizes the GABA analogs of Formula II, and these are described in U.S. Patent 5,563,175 which is incorporated herein by reference.
  • All that is required to practice the method of this invention is to administer a GABA analog and a decongestant in an amount that is effective to treat the sinus headache or sinus pain.
  • the amount of the GABA analog will generally be from about 1 to about 300 mg per kg of subject body weight. Typical doses will be from about 10 to about 5000 mg per day for an adult subject of normal weight. It is expected that common doses that might be administered could be from 100 mg three times a day up to 600 mg four times a day.
  • Commercially available capsules of 100 mg, 300 mg and 400 mg of gabapentin can be administered. Alternate forms include liquids and film-coated tablets.
  • the dosage level is one sixth that of gabapentin.
  • the dosage range for pregabalin is from about 0.15 mg to about 50 mg per kg per day of subject body weight. Typical dosages for pregabalin will be from about 1.6 mg to about 840 mg per day with individual dosages ranging from abut 0.15 mg to about 65 mg per dose.
  • a therapeutically effective decongestant amount of a sympathomimetic drug is that amount which produces the desired decongestant therapeutic response upon oral administration and can be readily determined by one skilled in the art by the use of conventional techniques and by observing results obtained under analogous circumstances. In determining the therapeutically effective amount, a number of factors are considered, including but not limited to: the particular compound administered; the bioavailability characteristics of the pharmaceutical composition administered; the dose regimen selected; and other relevant circumstances.
  • a therapeutically effective decongestant amount of a sympathomimetic drug will vary from about 1 mg to about 200 mg. Preferred amounts will vary from about 5 mg to about 150 mg.
  • These sympathomimetic drugs are generally effective when administered orally in unit dosage form on a four times a day dosage schedule wherein the unit dosage form provides immediate-release of the active medicament.
  • the recommended dosage for pseudoephedrine hydrochloride in adults is 60 mg every 6 hr (q.i.d.).
  • unit dosage forms containing sympathomimetic drugs can be formulated to provide prolonged release of the active medicament so as to allow the effective daily dose to be administered on a less frequent dosage schedule.
  • the recommended dosage for pseudoephedrine hydrochloride in a prolonged-release formulation can be 120 mg. b.i.d.
  • compositions according to the present invention can be administered concomitantly with antihistamines for relief of nasal congestion associated with allergic rhinitis.
  • antihistamines include, but are not limited to, the following: chlorpheniramine, brompheniramine, dexchlorpheniramine, dexbrompheniramine, tripolidine, diphenhydramine, doxylamine, tripelennamine, cyproheptadine, carbinoxamine, bromodiphenhydramine, phenindamine, pyrilamine, azatadine, terfenadine, astemizole, loratadine, acrivastine, cetirizine, azalastine, evastine, levocabastine, and pharmaceutically acceptable salts thereof.
  • compositions of the present invention can also include a second pain reliever.
  • pain relievers include analgesics such as aspirin, acetaminophen, ibuprofen, flurbiprofen, naproxen, mefenamic acid, ketoprofen, indomethacin, indoprofen, azapropazone, dicclofenac, difluisal, fenbufen, fenoprofen, piroxicam, sulindac, suprofen, tiaprofenic acid, tolmetin, droxicam, meloxicam, tenoxicam, etodolac, oxindanac or mixtures thereof.
  • analgesics such as aspirin, acetaminophen, ibuprofen, flurbiprofen, naproxen, mefenamic acid, ketoprofen, indomethacin, indoprofen, azapropazone
  • compositions of the present invention can also include an antitussive such as, but not limited to, the following: dextromethorphan, codeine, terpin hydrate and pharmaceutically acceptable salts thereof.
  • an antitussive such as, but not limited to, the following: dextromethorphan, codeine, terpin hydrate and pharmaceutically acceptable salts thereof.
  • compositions of the present invention can also include an expectorant.
  • the expectorants useful in the present invention include, but are not limited to, the following: guaifenesin, potassium guaicolsulfonate, potassium iodide, potassium citrate, iodinated glycerol, acetylcysteine, carboxymethylcysteine, ambroxol, sobrerol, and pharmaceutically acceptable salts thereof.
  • the GABA compounds of the present invention may form pharmaceutically acceptable salts with both organic and inorganic acids or bases.
  • the acid addition salts of the basic compounds are prepared either by dissolving the free base in aqueous or aqueous alcohol solution or other suitable solvents containing the appropriate acid and isolating the salt by evaporating the solution.
  • pharmaceutically acceptable salts are hydrochlorides, hydrobromides, hydrosulfates, etc. as well as sodium, potassium, and magnesium, etc. salts.
  • the compounds of Formula II can contain one or several asymmetric carbon atoms.
  • the invention includes the individual diastereomers or enantiomers, and the mixtures thereof.
  • the individual diastereomers or enantiomers may be prepared or isolated by methods already well-known in the art.
  • compositions of the compound of the present invention or its salts are produced by formulating the active compound in dosage unit form with a pharmaceutical carrier.
  • dosage unit forms are tablets, capsules, pills, powders, aqueous and nonaqueous oral solutions and suspensions, and parenteral solutions packaged in containers containing either one or some larger number of dosage units and capable of being subdivided into individual doses.
  • suitable pharmaceutical carriers are gelatin capsules; sugars such as lactose and sucrose; starches such as corn starch and potato starch, cellulose derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, methyl cellulose, and cellulose acetate phthalate; gelatin; talc; stearic acid; magnesium stearate; vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, and oil of theobroma; propylene glycol, glycerin; sorbitol; polyethylene glycol; water; agar; alginic acid; isotonic saline, and phosphate buffer solutions; as well as other compatible substances normally used in pharmaceutical formulations.
  • the compositions of the invention can also contain other components such as coloring agents, flavoring agents, and/or preservatives. These materials, if present, are usually used in relatively small amounts.
  • the compositions can, if desired, also contain other therapeutic agents.
  • the percentage of the active ingredients in the foregoing compositions can be varied within wide limits, but for practical purposes it is preferably present in a concentration of at least 10% in a solid composition and at least 2% in a primary liquid composition.
  • the most satisfactory compositions are those in which a much higher proportion of the active ingredient is present.
  • GABA analogs or their salts are oral or parenteral.
  • a useful intravenous dose is between 5 and 50 mg of GABA analog and a useful oral dosage of GABA analog is between 20 and 800 mg.
  • the dosage is within the dosing range used in treatment of pain or as would be with the needs of the patient as described by the physician.
  • the advantages of using the compounds of Formula I and II, especially gabapentin and pregabalin, in the instant invention include the relatively nontoxic nature of the compounds, the ease of preparation, the fact that the compounds are well-tolerated, and the ease of IV administration of the drugs.
  • Gabapentin has few interactions with major classes of drugs since it is not metabolized in the liver, but rather excreted unchanged from the body. Further, the drugs are not metabolized in the body.
  • the subjects treated with the method of the present invention are mammals, including humans.

Landscapes

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

Abstract

Cette invention porte sur une composition et la méthode afférente visant à traiter des céphalées des sinus ou des douleurs localisées dans les sinus, laquelle composition renferme des analogues d'acide glutamique et d'acide gamma-aminobutyrique associés à un décongestionnant.
EP99928815A 1998-07-09 1999-06-18 Compositions renfermant des analogues d'acide gamma-aminobutyrique (gaba) et un decongestionnant destinees a soulager des cephalees localisees dans les sinus Withdrawn EP1093365A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US9214698P 1998-07-09 1998-07-09
US92146P 1998-07-09
PCT/US1999/013946 WO2000002545A2 (fr) 1998-07-09 1999-06-18 Compositions renfermant des analogues d'acide gamma-aminobutyrique (gaba) et un decongestionnant destinees a soulager des cephalees localisees dans les sinus

Publications (1)

Publication Number Publication Date
EP1093365A2 true EP1093365A2 (fr) 2001-04-25

Family

ID=22231857

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99928815A Withdrawn EP1093365A2 (fr) 1998-07-09 1999-06-18 Compositions renfermant des analogues d'acide gamma-aminobutyrique (gaba) et un decongestionnant destinees a soulager des cephalees localisees dans les sinus

Country Status (12)

Country Link
EP (1) EP1093365A2 (fr)
JP (1) JP2002520276A (fr)
KR (1) KR20010074682A (fr)
AU (1) AU758103B2 (fr)
BR (1) BR9911943A (fr)
CA (1) CA2332927A1 (fr)
ID (1) ID28972A (fr)
NO (1) NO20010118D0 (fr)
NZ (1) NZ508491A (fr)
PL (1) PL345703A1 (fr)
WO (1) WO2000002545A2 (fr)
ZA (1) ZA200007170B (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10048714A1 (de) * 2000-09-30 2002-04-11 Gruenenthal Gmbh 5-Amino-1-penlen-3-ol-Derivate
AU2003210486B2 (en) * 2002-01-16 2007-06-28 Endo Pharmaceuticals Inc. Pharmaceutical composition and method for treating disorders of the central nervous system
CA2578990A1 (fr) * 2004-09-07 2006-03-16 Pfizer Inc. Combinaison d'un agoniste du recepteur 5-ht(1) et d'un ligand alpha-2-delta pour traiter la migraine
JP2010088301A (ja) 2007-02-01 2010-04-22 Ajinomoto Co Inc Ｌ−アミノ酸の製造法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU1801483C (ru) * 1990-03-19 1993-03-15 Волгоградский государственный медицинский институт Композици , обладающа гипертензивным действием
US5478565A (en) * 1990-03-27 1995-12-26 Warner-Lambert Company Treatment of sinus headache
US5604260A (en) * 1992-12-11 1997-02-18 Merck Frosst Canada Inc. 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2
AU714980B2 (en) * 1996-07-24 2000-01-13 Warner-Lambert Company Llc Isobutylgaba and its derivatives for the treatment of pain

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0002545A2 *

Also Published As

Publication number Publication date
ID28972A (id) 2001-07-19
WO2000002545A2 (fr) 2000-01-20
JP2002520276A (ja) 2002-07-09
NO20010118L (no) 2001-01-08
WO2000002545A3 (fr) 2000-04-13
AU758103B2 (en) 2003-03-13
BR9911943A (pt) 2001-05-29
NZ508491A (en) 2003-09-26
KR20010074682A (ko) 2001-08-09
ZA200007170B (en) 2002-03-04
PL345703A1 (en) 2002-01-02
NO20010118D0 (no) 2001-01-08
AU4579999A (en) 2000-02-01
CA2332927A1 (fr) 2000-01-20

Similar Documents

Publication Publication Date Title
US6306910B1 (en) Use of Gaba-analogues for treating insomnia
JP2002520286A (ja) Ｇａｂａ類縁体及びカフェインを含んでなる組成物
EP1977745B1 (fr) Traitement pour l'incontinence
US20040002543A1 (en) Compositions comprising GABA analogs and a decongestant to relieve sinus headache pain
AU758103B2 (en) Compositions comprising GABA analogs and a decongestant to relieve sinus headache pain
US6680343B1 (en) Treatment of renal colic with GABA analogs
CA2332929C (fr) Composition pharmaceutique renfermant des analogues d'acide gamma-aminobutyrique (gaba) et un agent antiviral aux fins du traitement de syndromes radiculoganglionnaires
MXPA00011507A (en) Compositions comprising gaba analogs and a decongestant to relieve sinus headache pain
CA2367494A1 (fr) Combinaisons d'analogues d'acide glutamique et d'acide gamma-aminobutyrique (gaba) et de composes tricycliques permettant de traiter la depression
US20030045500A1 (en) Pharmaceutical composition containing GABA analogs and an antiviral agent to treat shingles
EP1094804B1 (fr) Traitement de coliques nephretiques au moyen d'analogues du gaba
MXPA00011509A (en) Method for the treatment of insomnia

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20010209

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL PAYMENT 20010209;LT PAYMENT 20010209;LV PAYMENT 20010209;MK PAYMENT 20010209;RO PAYMENT 20010209;SI PAYMENT 20010209

17Q First examination report despatched

Effective date: 20041008

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: WARNER-LAMBERT COMPANY LLC

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20050419