Pharmaceutical compositions of spiro-oxindole compound for topical administration and their use as therapeutic agents

Patent metadata

Field	Value
Publication number	US-9504671-B2
Application number	US-201113580129-A
Country	US
Kind code	B2
Filing date	Feb 25, 2011
Priority date	Feb 26, 2010
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

Abstract

This invention is directed to pharmaceutical compositions for topical administration to a mammal, wherein the pharmaceutical compositions comprise a spiro-oxindole compound, as an enantiomer, a racemate or a non-racemic mixture, or a pharmaceutically acceptable salt thereof. These pharmaceutical compositions are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions.

First claim

What is claimed is:

1. A pharmaceutical composition for topical administration to a mammal comprising two or more pharmaceutically acceptable excipients and a therapeutically effective amount of a spiro-oxindole compound having the following formula:

or a pharmaceutically acceptable salt thereof, wherein each pharmaceutically acceptable excipient is present in a concentration of from about 0.01% w/w to about 99% w/w, wherein the pharmaceutically acceptable excipients are selected from one or more solvents, one or more penetration enhancing agents, one or more stiffening agents, one or more ointment bases and, optionally, one or more antioxidants, and wherein a solvent is selected from PEG 400 or PEG 3350, a penetration enhancing agent is selected from diethylene glycol monoethyl ether, oleyl alcohol, or isopropyl myristate, a stiffening agent is stearyl alcohol, an ointment base is selected from PEG 400 or PEG 3350, and the antioxidant, if present, is butylated hydroxytoluene (BHT).

2. The pharmaceutical composition of claim 1 , comprising one or more antioxidants.

3. The pharmaceutical composition of claim 1 , wherein PEG 400 is present in a concentration of from about 30% w/w to about 70% w/w, diethylene glycol monoethyl ether is present in a concentration of from about 2% w/w to about 25% w/w, oleyl alcohol is present in a concentration of from about 1% w/w to about 10% w/w, isopropyl myristate is present in a concentration of from about 1% w/w to about 25% w/w, stearyl alcohol is present in a concentration of from about 0.1% w/w to about 10% w/w, BHT, if present, is present in a concentration of from about 0.01% w/w to about 2% w/w, and PEG 3350 is present in a concentration of from about 10% w/w to about 50% w/w.

4. The pharmaceutical composition of claim 3 , wherein PEG 400 is present in a concentration of from about 45% w/w to about 55% w/w, diethylene glycol monoethyl ether is present in a concentration of from about 5% w/w to about 15% w/w, oleyl alcohol is present in a concentration of from about 2.5% w/w to about 7.5% w/w, isopropyl myristate is present in a concentration of from about 2.5% w/w to about 7.5% w/w, stearyl alcohol is present in a concentration of from about 0.1% w/w to about 7.5% w/w, BHT, if present, is present in a concentration of from about 0.05% w/w to about 1% w/w, and PEG 3350 is present in a concentration of from about 15% w/w to about 30% w/w.

5. The pharmaceutical composition of claim 4 , wherein the spiro-oxindole compound is present in a concentration of from about 0.1% w/w to about 10% w/w.

6. The pharmaceutical composition of claim 5 , wherein the spiro-oxindole compound is present in a concentration of from about 2% w/w to about 8% w/w.

7. 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.

8. 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 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. 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.

10. 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.

11. A method of inhibiting osteoarthritis, relieving osteoarthritis or relieving the symptoms of osteoarthritis in a mammal, wherein the method comprises topically administering to the mammal in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 1 .

12. The method of claim 11 , wherein the mammal is a human.

Assignees

• Winters Conrad Stewart
• Yang Meidong
• Chen Haigang
• Xenon Pharmaceuticals Inc

Inventors

• Winters Conrad Stewart
• Yang Meidong
• Chen Haigang

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/06

  Antimigraine agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title