PHOSPHODIESTERASE INHIBITOR TREATMENT
Methods and compositions are disclosed for the treatment of taste and smell disorders. The compositions comprise phosphodiesterase inhibitors and are formulated for intranasal administration.
1 .- 20 . (canceled)
21 . A method of treating a taste or smell disorder in a subject in need thereof comprising intranasal administration of one or more phosphodiesterase inhibitors using a multi-dose nasal spray device that delivers a dosage unit in a plume upon actuation, wherein the dosage unit comprises an effective amount of the one or more phosphodiesterase inhibitors in a pharmaceutically acceptable carrier comprising one or more excipients, wherein the taste or smell disorder is anosmia, hyposmia, ageusia, hypogeusia, or a combination thereof wherein the dosage unit does not comprise theophylline, and wherein the plume has a droplet size distribution characterized by the following:
(a) less than about 5% of the droplets in the plume having a size of less than about 10 μm,
(b) a D 10 of greater than about 12.5 μm, wherein about 10% of the droplets in the plume have a size less than the D 10 ,
(c) a D 50 of from about 30 to about 50 μm, wherein about 50% of the droplets in the plume have a size less than the D 50 ,
(d) a D 90 of from about 75 to about 100 μm, wherein about 90% of the droplets in the plume have a size less than the D 90 , and
(e) a span of from about 1 to about 6, wherein the span is calculated according to: (D 90 −D 10 )/D 50 .
22 .- 23 . (canceled)
24 . The method of claim 21 , wherein intranasal administration is once or twice daily to each naris.
25 . (canceled)
26 . The method of claim 21 , wherein the intranasal administration is each day for at least about 7 days.
27 .- 30 . (canceled)
31 . The method of claim 21 , wherein the subject experiences a clinically detectable improvement in taste or smell function within about 1-4 weeks of starting treatment.
32 .- 34 . (canceled)
35 . The method of claim 21 , wherein the droplet size distribution is characterized by less than about 4% of the droplets in the plume having a size of less than about 10 μm.
36 . The method of claim 21 , wherein the droplet size distribution is characterized by the D 10 of greater than about 15 μm.
37 . The method of claim 21 , wherein the droplet size distribution is characterized by the D 50 of from about 30 to about 40 μm.
38 . The method of claim 21 , wherein the droplet size distribution is characterized by the D 90 that is about 75 to about 85 μm.
39 . The method of claim 21 , wherein the droplet size distribution is characterized by the span of from about 1 to about 3.
40 . The method of claim 21 , wherein the one or more phosphodiesterase inhibitors comprise cilostazol, roflumilast, or a combination thereof.
41 . The method of claim 21 , wherein the one or more phosphodiesterase inhibitors are selected from the group consisting of nonselective phosphodiesterase inhibitors, phosphodiesterase 1 inhibitors, phosphodiesterase 2 inhibitors, phosphodiesterase 3 inhibitors, phosphodiesterase 4 inhibitors, phosphodiesterase 5 inhibitors, phosphodiesterase 10 inhibitors, and combinations thereof.
42 . The method of claim 21 , wherein the one or more phosphodiesterase inhibitors are selected from the group consisting of caffeine, aminophylline, paraxanthine, pentoxifylline, theobromine, oxphylline, cinpocetine, EHNA, inamrinone, anagrelide, cilostazol, mesembrine, rolipram, ibudilast, piclamilast, luteolin, drotaverine, roflumilast, sildenafil, tadalafil, vardenafil, udenafil, avanafil, dipyridamole, papaverine, and combinations thereof.
43 . The method of claim 21 , wherein the effective amount of one of the one or more phosphodiesterase inhibitors is, individually, from about 1 μg to about 200 μs.
44 . The method of claim 21 , wherein the effective amount of one of the one or more phosphodiesterase inhibitors is, individually, from about 0.02 μg/kg to about 3.3 μg/kg.
45 . The method of claim 21 , wherein the dosage unit is a steroid-free dosage unit.
46 . The method of claim 21 , wherein the plume has an ovality of about 1.
47 . The method of claim 21 , wherein the plume has a geometry of from about 45° to about 75°.
48 . The method of claim 21 , wherein the plume has a total liquid volume of from about 25 μL to about 200 μL.
49 . The method of claim 21 , wherein the taste or smell disorder is anosmia.
50 . The method of claim 21 , wherein the one or more phosphodiesterase inhibitors comprise roflumilast.
51 . The method of claim 21 , wherein the taste or smell disorder is hyposmia.
52 . The method of claim 21 , wherein the taste or smell disorder is ageusia.
53 . The method of claim 21 , wherein the taste or smell disorder is hypogeusia.