PIRFENIDONE/TOLL-LIKE RECEPTOR (TLR) AGONIST COMPOSITIONS AND METHODS FOR USING THEM TO STIMULATE PRODUCTION OF GRANULOCYTE COLONIZING STIMULATING FACTOR (G-CSF)
The invention disclosed herein relates to compositions and methods for treating subjects suffering from or at risk of developing neutropenia. In some embodiments, the methods comprise administering to a subject suffering from or at risk of developing neutropenia, an effective amount of pirfenidone and one or more toll-like receptor (TLR) agonists.
1 . A method of treating or inhibiting neutropenia in a subject in need thereof, the method comprising administering to said subject a therapeutically effective amount of pirfenidone and one or more toll-like receptor (TLR) agonists.
2 . The method of claim 1 , wherein the subject is a human.
3 . The method of claim 1 , wherein said administering comprises administering pirfenidone and said one or more TLR agonists in an amount effective for increasing the number of neutrophils in the subject.
4 . The method of claim 1 , wherein the therapeutically effective amount is less than 50% of an amount that causes an undesirable side effect in the subject.
5 .- 7 . (canceled)
8 . The method of claim 1 , wherein said administering comprises orally administering pirfenidone and said one or more TLR agonists.
9 .- 10 . (canceled)
11 . The method of claim 1 , wherein the administering comprises administering twice per day.
12 . The method of claim 1 , wherein the administering comprises administering three times per day.
13 . The method of claim 1 , wherein the administering comprises providing the pirfenidone in a dose of from about 100 to about 400 milligrams.
14 . The method of claim 1 , wherein the administering comprises administering the pirfenidone such that the daily intake is from about 800 to about 4000 mg/day.
15 . The method of claim 1 , wherein said administering comprises administering the pirfenidone such that the daily intake is about 1200 mg/day or higher.
16 . The method of claim 1 , wherein said neutropenia is severe neutropenia.
17 . The method of claim 1 , wherein said neutropenia is selected from the group consisting of neutropenia associated with chemotherapy, neutropenia associated with conventional oncology therapy, drug-induced neutropenia, disease-induced neutropenia, genetic neutropenia, toxin-induced neutropenia, congenital neutropenia, cyclic neutropenia, idiopathic neurtropenia, and radiation-induced neutropenia.
18 .- 21 . (canceled)
21 . The method of claim 1 , wherein the one or more TLR agonists comprises at least one TLR7 agonist.
22 . The method of claim 21 , wherein the TLR 7 agonist is selected from the group consisting of 7-thia-8-oxoguanosine, 7-deazaguanosine, 7-allyl-8-oxoguanosine, 7-dezaguanosine, imiquimod, and R848.
23 .- 49 . (canceled)
50 . A composition comprising a therapeutically effective amount of pirfenidone co-formulated with one or more toll-like receptor agonists.
51 . The composition of claim 50 , wherein said effective amount of pirfenidone is an amount effective for increasing the number of neutrophils in a subject.
52 . The composition of claim 50 , wherein the effective amount is less than 50% of an amount that causes an undesirable side effect in a subject.
53 . (canceled)
54 . The composition of claim 50 , wherein the composition is for oral administration.
55 . (canceled)
56 . The composition of claim 50 , wherein the pirfenidone is in a dose of from about 100 to about 400 milligrams.
57 . The composition of claim 50 , wherein the one or more TLR agonists comprises at least one TLR7 agonist.
58 . The composition of claim 57 , wherein the TLR 7 agonist is selected from the group consisting of 7-thia-8-oxoguanosine, 7-deazaguanosine, 7-allyl-8-oxoguanosine, 7-dezaguanosine, imiquimod, and R848.
59 .- 60 . (canceled)