WO1999037296A1 - Gabapentine et ses derives pour le traitement de la douleur musculaire et squelettique - Google Patents

Gabapentine et ses derives pour le traitement de la douleur musculaire et squelettique Download PDF

Info

Publication number
WO1999037296A1
WO1999037296A1 PCT/US1999/001290 US9901290W WO9937296A1 WO 1999037296 A1 WO1999037296 A1 WO 1999037296A1 US 9901290 W US9901290 W US 9901290W WO 9937296 A1 WO9937296 A1 WO 9937296A1
Authority
WO
WIPO (PCT)
Prior art keywords
pain
gabapentin
day
muscular
treatment
Prior art date
Application number
PCT/US1999/001290
Other languages
English (en)
Inventor
Leslie Magnus-Miller
Catherine A. Segal
Original Assignee
Warner-Lambert Company
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 Company filed Critical Warner-Lambert Company
Priority to AU24630/99A priority Critical patent/AU2463099A/en
Priority to CA002309354A priority patent/CA2309354A1/fr
Priority to EP99904178A priority patent/EP1047414A1/fr
Publication of WO1999037296A1 publication Critical patent/WO1999037296A1/fr

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
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid

Definitions

  • the present invention relates to the use of analogs of glutamic acid and gamma-aminobutyric acid (GABA) for the treatment of muscular and skeletal pain. More particularly, the invention relates to the use of gabapentin for the treatment of non-neuropathic muscular and skeletal pain.
  • GABA gamma-aminobutyric acid
  • the compounds of the invention 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
  • 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 specific what forms of pain are treated.
  • the compounds of the invention are known for treatment of neuropathic pain. For example, see Rosner H; Rubin L; Kestenbaum A.,
  • Gabapentin adjunctive therapy in neuropathic pain states Clin J Pain, 1996 Mar, 12:1, 56-8; Segal AZ; Rordorf G., Gabapentin as a novel treatment for postherpetic neuralgia. Neurology, 1996 Apr, 46:4, 1175-6; Wetzel CH; Connelly JF., Use of gabapentin in pain management. Ann Pharmacother, 1997 Sep, 31:9, 1082-3; Zapp JJ., Postpoliomyelitis pain treated with gabapentin [letter]. Am Fam -2- Physician, 1996 Jun, 53:8, 2442, 2445; Cheville A, et al., Neuropathic pain in radiation myelopathy: a case report.
  • Pain, 1997 Sept, 1393), pp. 251-3 discloses a retrospective review of patients that were treated with gabapentin. One of the groups of patients was reported to have low back pain. These patients did not report improved pain scores after using gapapentin.
  • Muscular and skeletal pain is caused by a variety of physical injuries or damage to the muscles, bones and tissues of the body.
  • a particularly debilitating form of this pain is chronic lower back pain.
  • Chronic lower back pain is a general condition of pain related to physical damage to the muscles (eg, muscle trauma or overexertion), bones (eg, osteoarthritis of the lumber spine) and/or tissues (eg, fibromyalgia) of the back.
  • Low back pain can also result from inflammation of the axial skeleton (eg, ankylosing spondylitis), conditions that create physical pressure on the nerves and tissues surrounding the spine (eg, sciatica and degenerative disk disease), or conditions/treatments that directly damage nerve -3- tissue (eg, postpoliomyelitis and chronic progressive radiation myelopathy [CPRM]).
  • inflammation of the axial skeleton eg, ankylosing spondylitis
  • conditions that create physical pressure on the nerves and tissues surrounding the spine eg, sciatica and degenerative disk disease
  • conditions/treatments that directly damage nerve -3- tissue eg, postpoliomyelitis and chronic progressive radiation myelopathy [CPRM]
  • neuropathic pain is chronic pain that can develop after alteration and/or injury to any level of the nervous system, peripheral or central.
  • the pain is typically burning and is associated with pressure on a nerve and/or actual damage to nervous tissue.
  • Some types of chronic low back pain can have a neuropathic component (eg, sciatica, postpoliomyelitis and CPRM).
  • Neuropathic conditions that have been treated with gabapentin include: postherpetic neuralgia, postpoliomyelitis, CPRM, HIV-related neuropathy, trigeminal neuralgia, diabetic neuropathy and Reflex Sympathetic Dystrophy (RSD). Of these, the cases of postpoliomyelitis and CPRM had pain associated with the back.
  • the main distinction between back pain that is neuropathy in nature, and muscular/skeletal lower back pain is that nerve damage itself is the cause of pain. In the other conditions, properly working nerves are detecting body tissue damage and pressure secondary to inflammation.
  • the two neuropathic conditions that reported a low back pain component clearly had the formation of anomalous nerve tissue or remodelling of the nerve pathway as the cause of pain.
  • Musculoskeletal pain is the unpleasant experience created by disease or dysfunction in the muscles, connective tissues, or by the stretching of the natural coverings of bones and joints. This type of condition can occur even when the associated sensory nerve fibers, by which the nociceptive impulses are sent from muscular tissue to the brain, are fully normal.
  • neuropathic pain is the sensation created when any combination of pathophysiological processes causes sensory nerves to function badly, or in a hyperexcitable manner.
  • One of the notable characteristics of neuropathic pain is that it can create the sensation that the source of symptoms is within its associated tissue, even when the nonneural tissue is perfectly healthy.
  • neuropathic pain There are patients whose low back pain may be predominantly musculoskeletal or neuropathic. In other patients the resulting symptoms are due to some degree of dysfunction of both types.
  • joints including the spinal facets, may be twisted and become inflamed.
  • Paraspinal muscles may be stretched to the point of having small penetrating vessels torn within the muscle tissue. Consequently the tissue repair response may create the lying down of multiple small areas of scar tissue within the muscle, which can stimulate further pain symptoms during contraction.
  • ligaments may be stretched and their sites of attachment may be torn away leaving microscopic hemorrhages and spinal instability.
  • Disc materials may be twisted in a manner where undue pressure from -5- above causing an actual internal shift of the nuclear material, resulting in a bulging or distortion of the shape of the disc.
  • disc capsules do not have adequate innervation to produce clinical pain when they are mechanically displaced, it has been confirmed that the posterior aspects of discs do indeed have innervation which creates pain when the disc capsule (annulus fibrosis) is stretched. Severe or sudden mechanical force can cause its jelly-like contents (nucleus pulpous) to shift and create pressure gradients against the inside wall of the disc capsule (annulus fibrosis) great enough for the disc to rupture.
  • the disc material Once the disc material is extruded outside its usual boundaries, it can put pressure on the nerve roots that are attempting to exit from the spinal canal. If enough of the disc material is ruptured or protruding, it may place true mechanical compression on the blood vessels which provide nutrition and oxygen to the nerve (versa nervure). The resulting schema will then make the nerve root dysfunctional, creating a specific form of neuropathic pain known as radiculopathy.
  • Reflex Sympathetic Dystrophy is a form of neuropathic pain that persists long after the cessation of cellular damage or healing of a physical injury. It is characterized by a severe burning pain secondary to autonomic (increased sympathetic activity) and/or dystrophic (skin and bone atrophy, increased hair and nail growth, cellular fibrosis, and possible alterations in cellular norepinephrine and sympathetic receptor sensitivity) changes in the tissue of the affected region. Such pain in the absence of any ongoing tissue damage along with the autonomic and/or dystrophic changes are distinguishing characteristics from conditions causing general low back pain. Moreover, the continued pain of RSD is typically out of proportion to the initial tissue damage and generally affects an extremity (eg, right shoulder and arm). -6-
  • the current treatments for lower back pain include exercise, spinal manipulation, bed rest, traction and/or drug therapy.
  • Drugs used to treat lower back pain include acetaminophen, tizanidine, mefenamic acid, chlormethoxazone, -paracetamol, ethoheptazine-aspirin-meprobamate, piroxicam, diflunisal, naproxen sodium, tricyclic antidepressants, indomethacin, cyclobenzaprine, baclofen and ibuprofen.
  • gabapentin which was originally used for treating the neurological disorder epilepsy, and has been further used to treat neurologically based pain (neuropathic pain), to treat muscular/skeletal based pain, such as chronic lower back pain.
  • neurologically based pain neuroopathic pain
  • muscular/skeletal based pain such as chronic lower back pain.
  • gabapentin been studied in low back pain conditions where the nervous system is functioning normally.
  • This invention provides a method for treating muscular and skeletal pain comprising administering to a subject suffering from such pain an effective amount of a GABA analog.
  • a preferred embodiment utilizes a cyclic amino acid compound of Formula I
  • R ⁇ 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 Rj is hydrogen and n is 4, which compound is l-(aminomethyl)-cyclohexane acetic acid, known generically as gabapentin. -7-
  • the invention includes treating muscular and skeletal pain with a compound of Formula II.
  • Ri is a straight or branched alkyl of from 1 to 6 carbon atoms, phenyl, or cycloalkyl of from 3 to 6 carbon atoms; R is hydrogen or methyl; and
  • R3 is hydrogen, methyl, or carboxyl.
  • Preferred compounds of the invention are those wherein R3 and R 2 are hydrogen, and Rj is -(CH 2 )o- 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.
  • a GAB A 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 GAB A 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 -8- incorporated herein by reference.
  • All that is required to practice the method of this invention is to administer a GABA analog in an amount that is effective to treat the muscular and/or skeletal pain.
  • Such anti-pain amount 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 for muscular and skeletal pain 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, 600 mg and 800 mg of gabapentin can be administered. Alternate forms include liquids and commercially available film- coated tablets.
  • the 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 the 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.
  • Formulating the active compound in dosage unit form with a pharmaceutical carrier produces pharmaceutical compositions useful in the present invention.
  • 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. -9-
  • 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.
  • a useful intravenous dose is between 5 and 50 mg and a useful oral dosage 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.
  • a unit dosage form of the GAB A analog to be used in this invention may also comprise other compounds useful in the treatment of pain.
  • the advantages of using the compounds of Formula I and II, especially gabapentin and pregabalin, in the present invention include the relatively nontoxic nature of the compounds, the ease of preparation and the fact that the compounds -10- are well-tolerated. 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.
  • This 50 year old Caucasian female patient was referred for diagnosis and management of her chief complaint of aching and fatigue and persistent muscle -11- pain on a daily basis, with secondary or comorbid complaints of her legs jerking at night, as well as an intermittent band like pain around her head.
  • the headache was described as band-like.
  • the timing was continuous, with frequent variations in severity.
  • the pain intensity of most areas was reported, using a standard Numeric Rating Scale (NRS-11, with zero being no pain and 10 representing the worst pain imaginable) as 4-6.
  • the pain was made worse with exercise, during cold weather and generally increased at night. No specific agents or activities made the pain any better.
  • Other symptoms included tingling of both feet.
  • Past medical history was positive for the usual childhood illnesses, but otherwise negative.
  • Family history was positive for arthritis, heart disease and hypertension.
  • Social history was negative for tobacco or alcohol.
  • the allergy history was positive for codeine, meperidine (Demerol), carisoprodol (Soma) and penicillin.
  • the patient's weight was 150 pounds, height was 5'1".
  • Vital signs at the initial visit were: Pulse-68 per minute, BP (Right arm sitting)- 122/70, -12- Respirations- 12 and p.o. Temperature- 97.2 F
  • Myofascial pain syndrome versus fibromyalgia syndrome Myofascial pain syndrome versus fibromyalgia syndrome, paraspinal muscle spasm, cervical radiculopathy, lumbar radiculopathy.
  • musculoskeletal pain (Myofascial pain syndrome vs. fibromyalgia) with radiographic evidence for degenerative changes of the cervical spine, with secondary independent root irritation created by the associated neuroforaminal narrowing.
  • the patient had previously been unresponsive to OTC preparations such as acetaminophen and ibuprofen, and had been allergic to codeine, meperidine and carisoprodol. While diagnostic tests were being conducted she was provided a therapeutic trial of tizanidine hcl (Zanaflex) for her painful muscle spasms. This was titrated upward over several days from 1 mg three times a day to 4 mg three times a day. At her follow-up appointment six weeks later she stated that she had noticed some improvement (up to 25% pain reduction)in her myofascial symptoms, but she could not tolerate the usual dose due to significant drowsiness. She therefore had to reduce the tizanidine hcl to 1 mg at breakfast and lunch and 4 mg at bedtime, which reduced the effectiveness of the treatment.
  • OTC preparations such as acetaminophen and ibuprofen
  • This 67 year old Caucasian female patient was referred for diagnosis and management of her chief complaint of multiregional pain involving intrascapular, thoracic and lumbar areas, with secondary or comorbid complaints of generalized weakness, as well as right sided neck pain and upper extremity paresthesias.
  • Past medical history was positive for the usual childhood illnesses, headaches, hypertension and arthritis.
  • Family history was positive for arthritis, heart disease and hypertension.
  • Social history was negative for alcohol but the patient does smoke one ppd.
  • the allergy history was positive for morphine, meperidine (Demerol), tetracycline and "all arthritis medications”.
  • the patient's weight was 170 pounds, height was 5 '5".
  • Vital signs at the initial visit were: Pulse-64 per minute, BP (Right arm sitting)-148/88,
  • Cranial nerves including fundi, were normal. Upper extremity bulk, power, tone and range of motion were normal. Power was 4/5-5/5 in most muscle groups, but pain and soreness were noted by the patient. Reflexes were mildly reduced in both upper extremities, but patellars were reduced and achilles reflexes were absent bilaterally. Plantar reflexes were normal. Sensory examination revealed local hyperesthesia to touch and light palpation but was within normal limits to cold and pin. Vibration was mildly reduced bilaterally below the ankles. Stance and gait were within normal limits.
  • Myofascial pain syndrome versus fibromyalgia syndrome Myofascial pain syndrome versus fibromyalgia syndrome, paraspinal muscle spasm, cervical radiculopathy, lumbar radiculopathy.
  • Needle EMGs of the upper extremities revealed mild C5-6 root irritation on the left and mild C3-4 irritation on the right, but lower extremity EMGs were normal. Nerve Conduction Velocity studies of both upper and both lower extremities were fully normal. MRI revealed prominent bulging discs at C4-5 and C5-6, and moderately bulging discs at C3-4 and C6-7, but no disc herniation or spinal stenosis.
  • musculoskeletal pain (Myofascial pain syndrome vs. fibromyalgia) with radiographic evidence for changes of the cervical spine associated with bulging intervertebral discs.
  • Treatment -17- The patient had previously been unresponsive to OTC preparations such as acetaminophen, and had not had any significant benefit from codeine containing compounds (Tylenol # 3, four times a day). She had been taking Robaxin 750 mg twice a day, which was tapered and discontinued due to its ineffectiveness. While diagnostic tests were being conducted she was provided a therapeutic trial of tizanidine Hcl (Zanaflex) for her aching and for painful muscle spasms. This was initiated at a low dose ( lmg three times a day) due to the patient's concerns about drowsiness.
  • the patient indicated that, since she had reduced her gabapentin from 1500 mg a day to 1200 mg a day that she noticed some slight and transient return of her symptoms. She requested that she be permitted to increase it back to 1500 mg a day. She has since remained essentially asymptomatic on the previous schedule. Her personal and pharmacy records indicate that she is not taking any narcotic analgesics.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé visant à utiliser certains analogues d'acide glutamique et d'acide gamma-aminobutyrique afin de soulager la douleur du dos de nature musculaire ou squelettique.
PCT/US1999/001290 1998-01-23 1999-01-22 Gabapentine et ses derives pour le traitement de la douleur musculaire et squelettique WO1999037296A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU24630/99A AU2463099A (en) 1998-01-23 1999-01-22 Gabapentin and its derivatives for the treatment of muscular and skeletal pain
CA002309354A CA2309354A1 (fr) 1998-01-23 1999-01-22 Gabapentine et ses derives pour le traitement de la douleur musculaire et squelettique
EP99904178A EP1047414A1 (fr) 1998-01-23 1999-01-22 Gabapentine et ses derives pour le traitement de la douleur musculaire et squelettique

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US7239798P 1998-01-23 1998-01-23
US60/072,397 1998-01-23

Publications (1)

Publication Number Publication Date
WO1999037296A1 true WO1999037296A1 (fr) 1999-07-29

Family

ID=22107298

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/001290 WO1999037296A1 (fr) 1998-01-23 1999-01-22 Gabapentine et ses derives pour le traitement de la douleur musculaire et squelettique

Country Status (4)

Country Link
EP (1) EP1047414A1 (fr)
AU (1) AU2463099A (fr)
CA (1) CA2309354A1 (fr)
WO (1) WO1999037296A1 (fr)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002028816A1 (fr) * 2000-09-30 2002-04-11 Buschmann, Helmut Derives 5-amino-1-pentene-3-ol substitues
EP1199072A2 (fr) * 2000-10-17 2002-04-24 Warner-Lambert Company Méthodes de traitement des lésions du cartilage
US6818787B2 (en) 2001-06-11 2004-11-16 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
US6833140B2 (en) 2001-06-11 2004-12-21 Xenoport, Inc. Orally administered dosage forms of GABA analog prodrugs having reduced toxicity
US6903130B1 (en) 1999-12-01 2005-06-07 Ucb S.A. Pyrrolidineacetamide derivative alone or in combination for treatment of cns disorders
US6927036B2 (en) 2002-02-19 2005-08-09 Xero Port, Inc. Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof
US7060727B2 (en) 2002-12-11 2006-06-13 Xenoport, Inc. Prodrugs of fused GABA analogs, pharmaceutical compositions and uses thereof
US7183259B2 (en) 2002-05-17 2007-02-27 Xenoport Amino acid conjugates providing for sustained systemic concentrations of GABA analogues
WO2007108001A2 (fr) * 2006-03-22 2007-09-27 Haim Dror Blecher Remodelage de ligament
US7393872B2 (en) 1999-04-09 2008-07-01 Euro-Celtique S.A. Sodium channel blocker compositions and the use thereof
US7420002B2 (en) 2001-06-11 2008-09-02 Xenoport Amino acid conjugates providing for sustained systemic concentrations of GABA analogues
US7462630B2 (en) * 2001-08-31 2008-12-09 Ajinomoto Co., Inc. Diarylalkene derivatives and novel diarylalkane derivatives
US7790708B2 (en) 2001-06-11 2010-09-07 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
US20110039875A1 (en) * 2007-08-06 2011-02-17 Trinity Laboratories, Inc. Pharamaceutical compositions for treating chronic pain and pain associated with neuropathy
US8026279B2 (en) 2003-10-14 2011-09-27 Xenoport, Inc. Crystalline form of γ-aminobutyric acid analog
US8048917B2 (en) 2005-04-06 2011-11-01 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
US8084447B2 (en) 2001-09-03 2011-12-27 Newron Pharmaceuticals S.P.A. Pharmaceutical composition comprising gabapentin or an analogue thereof and an α-aminoamide and its analgesic use
US8114909B2 (en) 2003-09-17 2012-02-14 Xenoport, Inc. Treating or preventing restless legs syndrome using prodrugs of GABA analogs
US8795725B2 (en) 2004-11-04 2014-08-05 Xenoport, Inc. GABA analog prodrug sustained release oral dosage forms
EP4227293A2 (fr) 2018-05-14 2023-08-16 Xgene Pharmaceutical Inc Formes cristallines de conjugués médicament-carbamate de 1-(acyloxy)-alkyle de naproxène et de prégabaline

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1465229A (en) * 1974-12-21 1977-02-23 Warner Lambert Co Cyclic amino acids
WO1998019674A2 (fr) * 1996-11-05 1998-05-14 Head Explorer Aps Procede de traitement de cephalees du type par tension nerveuse
WO1998046601A1 (fr) * 1997-04-11 1998-10-22 Eli Lilly And Company Composition pour le traitement de la douleur
WO1998058641A1 (fr) * 1997-06-25 1998-12-30 Warner-Lambert Company Utilisation d'analogues de gaba, telle la gabapentine, dans la fabrication d'un medicament servant a traiter des maladies inflammatoires

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1465229A (en) * 1974-12-21 1977-02-23 Warner Lambert Co Cyclic amino acids
WO1998019674A2 (fr) * 1996-11-05 1998-05-14 Head Explorer Aps Procede de traitement de cephalees du type par tension nerveuse
WO1998046601A1 (fr) * 1997-04-11 1998-10-22 Eli Lilly And Company Composition pour le traitement de la douleur
WO1998058641A1 (fr) * 1997-06-25 1998-12-30 Warner-Lambert Company Utilisation d'analogues de gaba, telle la gabapentine, dans la fabrication d'un medicament servant a traiter des maladies inflammatoires

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
"Postpoliomyelitis pain treated with gabapentin.", AMERICAN FAMILY PHYSICIAN, (1996) 53/8 (2442-2443). ISSN: 0002-838X CODEN: AFPYAE, United States, XP002101737 *
B. EPSTEIN ET AL.: "The Use of Gabapentin for Neuropathic and Musculoskeletal Pain: A Case Series", JOURNAL OF NEUROLOGIC REHABILITATION, vol. 12, no. 2, September 1998 (1998-09-01), pages 81 - 86, XP002101736 *
FIELD M J ET AL: "Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain.", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, (1997 SEP) 282 (3) 1242-6. JOURNAL CODE: JP3. ISSN: 0022-3565., United States, XP002101741 *
FIELD M J ET AL: "GABAPENTIN (NEURONTIN) AND S-(+)-3-ISOBUTYLGABA REPRESENT A NOVEL CLASS OF SELECTIVE ANTIHYPERALGESIC AGENTS", BRITISH JOURNAL OF PHARMACOLOGY, vol. 121, no. 8, 1997, pages 1513 - 1522, XP002043785 *
MELLICK G A ET AL: "GABAPENTIN IN THE MANAGEMENT OF REFLEX SYMPATHETIC DYSTROPHY", JOURNAL OF PAIN AND SYMPTOM MANAGEMENT, vol. 10, no. 4, May 1995 (1995-05-01), pages 265/266, XP002043783 *
MELLICK G A ET AL: "REFLEX SYMPATHETIC DYSTROPHY TREATED WITH GABAPENTIN", ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION, vol. 78, no. 1, January 1997 (1997-01-01), pages 98 - 105, XP002043784 *
MUELLER M E ET AL: "Gabapentin for relief of upper motor neuron symptoms in multiple sclerosis.", ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION, (1997 MAY) 78 (5) 521-4 JOURNAL CODE: 8BK. ISSN: 0003-9993., United States, XP002101740 *
ROSENBERG J M ET AL: "The effect of gabapentin on neuropathic pain.", CLINICAL JOURNAL OF PAIN, (1997 SEP) 13 (3) 251-5. JOURNAL CODE: BEG. ISSN: 0749-8047., United States, XP002101738 *
SHIMOYAMA, NAOHITO ET AL: "Spinal gabapentin is antinociceptive in the rat formalin test", NEUROSCI. LETT. (1997), 222(1), 65-67 CODEN: NELED5;ISSN: 0304-3940, 1997, XP002101742 *
WETZEL C H ET AL: "Use of gabapentin in pain management.", ANNALS OF PHARMACOTHERAPY, (1997 SEP) 31 (9) 1082-3. REF: 8 JOURNAL CODE: BBX. ISSN: 1060-0280., United States, XP002101739 *

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7393872B2 (en) 1999-04-09 2008-07-01 Euro-Celtique S.A. Sodium channel blocker compositions and the use thereof
US6903130B1 (en) 1999-12-01 2005-06-07 Ucb S.A. Pyrrolidineacetamide derivative alone or in combination for treatment of cns disorders
WO2002030869A1 (fr) * 2000-09-30 2002-04-18 Grünenthal GmbH Derives de 5-amino-1-penten-3-ol substitues
US6815443B2 (en) 2000-09-30 2004-11-09 Gruenenthal Gmbh 5-Amino-1-pentene-3-ol substituted derivatives
WO2002028816A1 (fr) * 2000-09-30 2002-04-11 Buschmann, Helmut Derives 5-amino-1-pentene-3-ol substitues
US7189747B2 (en) 2000-10-17 2007-03-13 Warner-Lambert Company Method of treating noninflammatory cartilage damage
EP1199072A2 (fr) * 2000-10-17 2002-04-24 Warner-Lambert Company Méthodes de traitement des lésions du cartilage
EP1199072A3 (fr) * 2000-10-17 2003-03-19 Warner-Lambert Company Méthodes de traitement des lésions du cartilage
US6620829B2 (en) 2000-10-17 2003-09-16 Warner-Lambert Company Method of treating noninflammatory cartilage damage
KR100427003B1 (ko) * 2000-10-17 2004-05-06 워너-램버트 캄파니 엘엘씨 연골 손상의 치료 방법
US8168623B2 (en) 2001-06-11 2012-05-01 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
EP2085087A1 (fr) 2001-06-11 2009-08-05 Xenoport, Inc. Promédicaments d'analogues gaba, compositions et leurs utilisations
US6818787B2 (en) 2001-06-11 2004-11-16 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
US9238616B2 (en) 2001-06-11 2016-01-19 Xenoport, Inc. Prodrugs of gaba analogs, compositions and uses thereof
US7790708B2 (en) 2001-06-11 2010-09-07 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
US6833140B2 (en) 2001-06-11 2004-12-21 Xenoport, Inc. Orally administered dosage forms of GABA analog prodrugs having reduced toxicity
US7420002B2 (en) 2001-06-11 2008-09-02 Xenoport Amino acid conjugates providing for sustained systemic concentrations of GABA analogues
US7645797B2 (en) 2001-06-11 2010-01-12 Xenoport, Inc. Amino acid conjugates providing for sustained systemic concentrations of GABA analogues
US8278329B2 (en) 2001-08-31 2012-10-02 Ajinomoto Co., Inc. Diarylalkene derivatives and novel diarylalkane derivatives
US7462630B2 (en) * 2001-08-31 2008-12-09 Ajinomoto Co., Inc. Diarylalkene derivatives and novel diarylalkane derivatives
US8710040B2 (en) 2001-09-03 2014-04-29 Newron Pharmaceuticals S.P.A. Pharmaceutical composition comprising gabapentin or an analogue thereof and an α-aminoamide and its analgesic use
US8084447B2 (en) 2001-09-03 2011-12-27 Newron Pharmaceuticals S.P.A. Pharmaceutical composition comprising gabapentin or an analogue thereof and an α-aminoamide and its analgesic use
US7560483B2 (en) 2002-02-19 2009-07-14 Xenoport, Inc. Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof
US8143437B2 (en) 2002-02-19 2012-03-27 Xenoport, Inc. Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof
US6927036B2 (en) 2002-02-19 2005-08-09 Xero Port, Inc. Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof
US7767649B2 (en) 2002-05-17 2010-08-03 Xenoport, Inc. Amino acid conjugates providing for sustained systemic concentrations of GABA analogues
US7183259B2 (en) 2002-05-17 2007-02-27 Xenoport Amino acid conjugates providing for sustained systemic concentrations of GABA analogues
US7060727B2 (en) 2002-12-11 2006-06-13 Xenoport, Inc. Prodrugs of fused GABA analogs, pharmaceutical compositions and uses thereof
US8114909B2 (en) 2003-09-17 2012-02-14 Xenoport, Inc. Treating or preventing restless legs syndrome using prodrugs of GABA analogs
US8026279B2 (en) 2003-10-14 2011-09-27 Xenoport, Inc. Crystalline form of γ-aminobutyric acid analog
US8686034B2 (en) 2003-10-14 2014-04-01 Xenoport, Inc. Crystalline form of γ-aminobutyric acid analog
US9150503B2 (en) 2003-10-14 2015-10-06 Xenoport, Inc. Crystalline form of γ-aminobutyric acid analog
US8795725B2 (en) 2004-11-04 2014-08-05 Xenoport, Inc. GABA analog prodrug sustained release oral dosage forms
US8906412B2 (en) 2004-11-04 2014-12-09 Xenoport, Inc. GABA analog prodrug sustained release oral dosage forms
US8048917B2 (en) 2005-04-06 2011-11-01 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
WO2007108001A3 (fr) * 2006-03-22 2007-12-06 Haim Dror Blecher Remodelage de ligament
WO2007108001A2 (fr) * 2006-03-22 2007-09-27 Haim Dror Blecher Remodelage de ligament
US20110039875A1 (en) * 2007-08-06 2011-02-17 Trinity Laboratories, Inc. Pharamaceutical compositions for treating chronic pain and pain associated with neuropathy
US10300031B2 (en) * 2007-08-06 2019-05-28 Trinity Laboratories Inc. Pharmaceutical compositions for treating chronic pain and pain associated with neuropathy
EP4227293A2 (fr) 2018-05-14 2023-08-16 Xgene Pharmaceutical Inc Formes cristallines de conjugués médicament-carbamate de 1-(acyloxy)-alkyle de naproxène et de prégabaline

Also Published As

Publication number Publication date
AU2463099A (en) 1999-08-09
EP1047414A1 (fr) 2000-11-02
CA2309354A1 (fr) 1999-07-29

Similar Documents

Publication Publication Date Title
WO1999037296A1 (fr) Gabapentine et ses derives pour le traitement de la douleur musculaire et squelettique
Mellick et al. Reflex sympathetic dystrophy treated with gabapentin
Brogden et al. Baclofen: a preliminary report of its pharmacological properties and therapeutic efficacy in spasticity
Matthews Paroxysmal symptoms in multiple sclerosis.
Rusy et al. Gabapentin in phantom limb pain management in children and young adults: report of seven cases
Biondi Cervicogenic headache: diagnostic evaluation and treatment strategies
US20060122127A1 (en) Methods for reducing the side effects associated with mirtzapine treatment
US20090137565A1 (en) Method for treatment of movement disorders
Sage Pain in Parkinson’s disease
CN104602689A (zh) 生物素治疗多发性硬化的用途
AU2009304002B9 (en) A medicinal product and treatment
Hardy Chronic pain management: the essentials
Witzke et al. Diabetic neuropathy in older adults
JP2000502318A (ja) Ｎ−Ｌ−α−アスパルチル−Ｌ−フェニルアラニン１−メチルエステルの鎮痛剤としての使用
US8975298B2 (en) Therapeutic agent for pain
MXPA00004734A (en) Gabapentin and its derivatives for the treatment of muscular and skeletal pain
Xia Conscious Sedation and Analgesia
Kung et al. Absolute case-based neurology review
Gervasoni Pain management with paracetamol and ibuprofen in combination
Borja Tapentadol for the management of neuropathic pain from oxaliplatin chemotherapy: A case report
Al-Mosawi Degenerative Lumber Spondylosis: An Educational Radiographs and Expert Therapeutic Recommendation
MURINOVA et al. Management of Headache Using an Integrative Approach
Jansen Common Pain Syndromes
Almahrezi et al. Intravenous Lidocaine for Refractory Chronic Orofacial Pain: Two case reports and a literature review
D'alessandro et al. An unusual case of electromyographic recorded myokymic potentials: A case report

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AU BA BB BG BR CA CN CU CZ EE GE HR HU ID IL IS JP KP KR LC LK LR LT LV MG MK MN MX NO NZ PL RO SG SI SK SL TR TT UA UZ VN YU

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref document number: 2309354

Country of ref document: CA

Ref country code: CA

Ref document number: 2309354

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: PA/a/2000/004734

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 1999904178

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: KR

WWP Wipo information: published in national office

Ref document number: 1999904178

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1999904178

Country of ref document: EP