Claims for Patent: 11,957,660

Summary for Patent: 11,957,660

Title:	Edaravone suspension for oral administration
Abstract:	An edaravone suspension for human oral administration includes edaravone particles, a dispersant, and water.
Inventor(s):	Tetsuo Hayama, Tomohiro Takahashi, Tomoyuki Omura, Kouji Hayashi, Munetomo Matsuda, Tadashi Miyazawa
Assignee:	Mitsubishi Tanabe Pharma Corp
Application Number:	US17/934,234
Patent Claims:	1. An edaravone suspension for human oral administration, comprising: water; a thickening agent comprising at least one of tragacanth powder and xanthan gum; edaravone particles comprising edaravone and dispersed in the water; and a dispersant dispersing the edaravone particles in the water such that the dispersant maintains the edaravone particles in a solid particle state in the water, wherein a blending amount of the edaravone particles is in a range of 0.2% (w/v) to 36% (w/v), and the edaravone suspension does not contain a preservative selected from the group consisting of methylparaben, ethylparaben, propylparaben, butylparaben, benzoic acid, sorbic acid, sodium benzoate, benzyl alcohol, phenylethanol and a combination thereof, and does not have a bacterial growth for at least 28 days according to the preservation efficacy test of Japanese Pharmacopeia. 2. The edaravone suspension according to claim 1, wherein the dispersant is a dispersant exhibiting a transmission scattering light intensity of 1% or more. 3. The edaravone suspension according to claim 1, wherein the dispersant is a dispersant exhibiting a contact angle of 80 degrees or less. 4. The edaravone suspension according to claim 1, wherein the dispersant is at least one dispersant selected from the group consisting of polyvinyl alcohol, sucrose fatty acid ester, polysorbate, methylcellulose, and hypromellose. 5. The edaravone suspension according to claim 1, wherein the dispersant is at least one of polyvinyl alcohol and methylcellulose. 6. The edaravone suspension according to claim 1, wherein the dispersant is polyvinyl alcohol. 7. The edaravone suspension according to claim 1, wherein a blending amount of the dispersant is in a range of 0.001% (w/v) to 1.0% (w/v). 8. The edaravone suspension according to claim 1, wherein the thickening agent is at least one of tragacanth powder and xanthan gum. 9. The edaravone suspension according to claim 1, wherein the thickening agent is xanthan gum. 10. The edaravone suspension according to claim 1, wherein a blending amount of the thickening agent is in a range of 0.1% (w/v) to 1.2% (w/v). 11. The edaravone suspension according to claim 1, wherein the edaravone suspension contains no preservative. 12. The edaravone suspension according to claim 1, further comprising: a stabilizer comprising at least one of a sulfite, a bisulfite, a pyrosulfite, a cysteine, a methionine, polyethylene glycol, polyoxyethlene polyoxypropylene glycol, and EDTA. 13. The edaravone suspension according to claim 12, wherein the stabilizer includes at least one of the sulfite, the bisulfite, the pyrosulfite, and the cysteine. 14. The edaravone suspension according to claim 12, wherein the stabilizer includes the bisulfite comprising sodium bisulfite. 15. The edaravone suspension according to claim 1, wherein when edaravone in the edaravone suspension is in a range of 90 to 120 mg, edaravone in a plasma exhibits a mean Cmax in a range of 500 to 2500 ng/mL and a mean AUC0-∞ in a range of 1000 to 2500 h*ng/mL when the edaravone suspension is orally administered to a human. 16. The edaravone suspension according to claim 1, wherein when edaravone in the edaravone suspension is in a range of 90 to 120 mg, and a crossover study is performed such that the edaravone suspension is orally administered to a human and that an edaravone injection is used as a control drug product, a lower limit of a 90% confidence interval of a ratio of a Cmax geometric mean value with respect to the control drug product and a lower limit of a 90% confidence interval of a ratio of an AUC0-∞ geometric mean value with respect to the control drug product both exceed 0.8. 17. The edaravone suspension according to claim 1, wherein when edaravone in the edaravone suspension is in a range of 90 to 120 mg, and a crossover study is performed such that the edaravone suspension is orally administered to a human and that an edaravone injection is used as a control drug product, a ratio of a Cmax geometric mean value with respect to the control drug product and a ratio of an AUC0-∞ geometric mean value with respect to the control drug product are both in a range of 0.8 to 1.25. 18. The edaravone suspension according to claim 1, wherein a blending amount of the thickening agent is in a range of 0.2% (w/v) to 1.0% (w/v). 19. The edaravone suspension according to claim 1, wherein a blending amount of the thickening agent is in a range of 0.3% (w/v) to 0.5% (w/v). 20. An ALS therapeutic agent, comprising: a drug product comprising edaravone and a thickening agent comprising at least one of tragacanth powder and xanthan gum, wherein a dose of the drug product per one oral administration is in a range of 1 to 20 mL and contains the edaravone in a range of 50 to 210 mg, and the dose of the drug product per one oral administration does not contain a preservative selected from the group consisting of methylparaben, ethylparaben, propylparaben, butylparaben, benzoic acid, sorbic acid, sodium benzoate, benzyl alcohol, phenylethanol and a combination thereof, and does not have a bacterial growth for at least 28 days according to the preservation efficacy test of Japanese Pharmacopeia.