Nova Patents
IL221646A

Pharmaceutical compositions of an (s)-enantiomer of a spiro-oxindole compound for topical administration and their use as therapeutic agents for inhibiting a sodium channel

Abstract

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Term

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  1. Priority
  2. Filed
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16 claims: 3 independent, 13 dependent

  1. 1
    43 221646/2 WHAT IS CLAIMED IS 1. A topical pharmaceutical composition comprising two or more pharmaceutically acceptable excipients and an effective amount of a spiro-oxindole compound having the following formula:1) a solvent selected from polyethylene glycol, diethylene glycol monoethyl ether, polysorbates, alcohols, carpylocaproyl macrogolglycerides, caprylic/capric triglyceride, fatty acid esters, diethyl sebacate, propylene glycol monocaprylate, propylene glycol laurate, mono diglycerides, glyceryl monocaprylate, medium chain triglycerides, hexylene glycol, glyceryl monooleate, 1,2-pentanediol, octyldodecanol, glyceryl mono-linoleate, glycerol oleate/propylene glycol, mineral oil, water, or glycerine;2) optionally, a penetration enhancing agent selected from dimethyl sulfoxide, decylmethylsulfoxide, laurocapram, pyrrolidones, surfactants, alcohols, oleic acid, polyethylene glycol, diethylene glycol monoethyl ether, or fatty acid esters;3) a stiffening agent selected from stearyl alcohol, carbopols, dimethicone or polymers;4) an ointment base selected from polyethylene glycols;and 5) optionally, an antioxidant selected from butylated hydroxytoluene, butylated hydroxyanisole, tocopherols, flavinoid, glutathione, ascorbic acid and esters, dimethyl sulfoxide, or chelating agents.
  2. 2
    The topical pharmaceutical composition of Claim 1, wherein each pharmaceutically acceptable excipient is present in a concentration of from 0.01% w/w to 99% w/w.
  3. 3
    The pharmaceutical composition of Claim 2, wherein a solvent is selected from PEG 400 or PEG 3350, a penetration enhancing agent, if present is selected from diethylene glycol monoethyl ether, oleyl alcohol, or isopropyl myristate, a stiffening agent is stearyl alcohol, 44 221646/2 an ointment base is selected from PEG 400 or PEG 3350, and the antioxidant, if present, is butylated hydroxytoluene.
  4. 4
    The pharmaceutical composition of Claim 3, wherein PEG 400 is present in a concentration of from 30% w/w to 70% w/w, diethylene glycol monoethyl ether, if present, is present in a concentration of from 2% w/w to 25% w/w, oleyl alcohol is present in a concentration of from 1% w/w to 10% w/w, isopropyl myristate is present in a concentration of from 1% w/w to 25% w/w, stearyl alcohol is present in a concentration of from 0.1% w/w to 10% w/w, butylated hydroxytoluene, if present, is present in a concentration of from 0.01% w/w to 2% w/w, and PEG 3350 is present in a concentration of from 10% w/w to 50% w/w.
  5. 5
    The pharmaceutical composition of Claim 4, wherein PEG 400 is present in a concentration of from 45% w/w to 55% w/w, diethylene glycol monoethyl ether, if present is present in a concentration of from 5% w/w to 15% w/w, oleyl alcohol is present in a concentration of from 2.5% w/w to 7.5% w/w, isopropyl myristate is present in a concentration of from 2.5% w/w to 7.5% w/w, stearyl alcohol is present in a concentration of from 0.1% w/w to 7.5% w/w, butylated hydroxytoluene, if present, is present in a concentration of from 0.05% w/w to 1% w/w, and PEG 3350 is present in a concentration of from 15% w/w to 30% w/w.
  6. 6
    The pharmaceutical composition of Claim 1, wherein the spiro-oxindole compound is present in a concentration of from 0.1% w/w to 10% w/w.
  7. 7
    The pharmaceutical composition of Claim 6, wherein the spiro-oxindole compound is present in a concentration of from 2% w/w to 8% w/w.
  8. 8
    The pharmaceutical composition of Claim 1 comprising the spiro-oxindole compound at a concentration of 2.0% w/w;PEG 400 at a concentration of 52.9% w/w;diethylene glycol monoethyl ether at a concentration of 10% w/w;oleyl alcohol at a concentration of 5% w/w;isopropyl myristate at a concentration of 5% w/w;stearyl alcohol at a concentration of 5% w/w;butylated hydroxytoluene at a concentration of 0.1% w/w;and PEG 3350 at a concentration of 20% w/w of the pharmaceutical composition.
  9. 9
    The pharmaceutical composition of Claim 1 comprising the spiro-oxindole compound at a concentration of 4% w/w;PEG 400 at a concentration of 50.9% w/w;diethylene 45 221646/2 glycol monoethyl ether at a concentration of 10% w/w;oleyl alcohol at a concentration of 5% w/w;isopropyl myristate at a concentration of 5% w/w;stearyl alcohol at a concentration of 5% w/w;butylated hydroxytoluene at a concentration of 0.1% w/w;and PEG 3350 at a concentration of 20% w/w of the pharmaceutical composition.
  10. 10
    The pharmaceutical composition of Claim 1 comprising the spiro-oxindole compound at a concentration of 4% w/w;PEG 400 at a concentration of 50.9% w/w;diethylene glycol monoethyl ether at a concentration of 5% w/w;oleyl alcohol at a concentration of 5% w/w;isopropyl myristate at a concentration of 5% w/w;stearyl alcohol at a concentration of 10% w/w;butylated hydroxytoluene at a concentration of 0.1% w/w;and PEG 3350 at a concentration of 20% w/w of the pharmaceutical composition.
  11. 11
    The pharmaceutical composition of Claim 1 comprising the spiro-oxindole compound at a concentration of 8% w/w;PEG 400 at a concentration of 46.9% w/w;diethylene glycol monoethyl ether at a concentration of 10% w/w;oleyl alcohol at a concentration of 5% w/w;isopropyl myristate at a concentration of 5% w/w;stearyl alcohol at a concentration of 5% w/w;butylated hydroxytoluene at a concentration of 0.1% w/w;and PEG 3350 at a concentration of 20% w/w of the pharmaceutical composition.
  12. 12
    Use of the pharmaceutical composition of any one of Claims 1 to 11 in the manufacture of a medicament for treating, preventing or ameliorating a sodium channel-mediated disease or a condition in a mammal in need thereof, wherein the medicament is topically administered to the mammal and wherein said disease or condition is selected from the group consisting of neuropathic pain, inflammatory pain, visceral pain, post-herpetic neuralgia, cancer pain, chemotherapy pain, trauma pain, surgical pain, post-operative pain, pruritis, osteoarthritis, trigeminal neuralgia, familial erythromelalgia, primary erythromelalgia, familial rectal pain, childbirth pain, labor pain, neurogenic bladder, ulcerative colitis, chronic pain, persistent pain, peripherally mediated pain, centrally mediated pain, chronic headache, migraine headache, sinus headache, tension headache, phantom limb pain, peripheral nerve injury, and combinations thereof.
  13. 13
    The use of Claim 12, wherein said disease or condition is selected from the group consisting of neuropathic pain, inflammatory pain, visceral pain, post-herpetic neuralgia, cancer pain, chemotherapy pain, trauma pain, surgical pain, post-operative pain, pruritis, 46 221646/2 osteoarthritis, trigeminal neuralgia, familial erythromelalgia, primary erythromelalgia, familial rectal pain, childbirth pain, labor pain, neurogenic bladder, ulcerative colitis, chronic pain, persistent pain, peripherally mediated pain, centrally mediated pain, chronic headache, migraine headache, sinus headache, tension headache, phantom limb pain, peripheral nerve injury, and combinations thereof.
  14. 14
    The use of Claim 12, wherein the mammal is a human.
  15. 15
    Use of the pharmaceutical composition of any one of Claims 1 to 11 in the manufacture of a medicament for treating pain through inhibition of ion flux through a voltage-dependent sodium channel in a mammal in need thereof, wherein the medicament is topically administered to the mammal.
  16. 16
    The use of Claim 15, wherein the mammal is a human. Dr. Revital Green Patent Attorney G.E. Ehrlich (1995) Ltd. 11 Menachem Begin Road 52 521 Ramat Gan
Independent claims16