TREATMENT OF BLADDER DISEASES WITH A TLR7 ACTIVATOR
The invention provides a method for the treatment of superficial bladder cancer and inflammatory diseases of the bladder which employs certain Toll-like Receptor (TLR)-agonists.
1 . A method to inhibit or treat superficial bladder cancer in a mammal, comprising administering intravesicularly to a mammal having superficial bladder cancer an effective amount of a composition comprising a TLR7 agonist formulated or chemically modified to inhibit systemic adsorption or to enhance local concentrations of the agonist in the bladder mucosa.
2 . The method of claim 1 wherein the composition comprises a chemically modified TLR7 agonist.
3 . The method of claim 2 wherein the modification is the covalent linkage of the TLR7 agonist to a protein or a lipid.
4 . The method of claim 1 wherein the composition comprises an emulsion.
5 . The method of claim 1 wherein the composition comprises nanoparticles.
6 . The method of claim 1 wherein the composition comprises liposomes.
7 . The method of claim 1 wherein the composition comprises nanocrystals.
8 . The method of claim 1 wherein a catheter is employed to administer the composition.
9 . The method of claim 1 further comprising applying ultrasound to the bladder.
10 . The method of claim 1 further comprising applying electromagnetic radiation to the bladder.
11 . The method of claim 1 further comprising applying a surfactant to the bladder.
12 . The method of claim 1 wherein the mammal is a human.
13 . The method of claim 1 wherein the mammal has elevated numbers of mast cells.
14 . The method of claim 1 wherein the mammal has elevated levels of neurokinin in the urine.
15 . The method of claim 1 wherein the mammal is post-transurethral resection.
16 . A method to inhibit or treat superficial bladder cancer in a mammal, comprising administering intravescicularly to a mammal having superficial bladder cancer an effective amount of a composition comprising a TLR7 agonist in conjunction with a treatment to enhance local concentrations of the agonist in the bladder mucosa.
17 . The method of claim 16 wherein the treatment comprises applying ultrasound to the bladder.
18 . The method of claim 16 wherein the treatment comprises applying electromagnetic radiation to the bladder.
19 . The method of claim 16 wherein the treatment comprises applying a surfactant to the bladder.
20 . The method of claim 16 wherein the mammal is a human.
21 . The method of claim 16 wherein the mammal has elevated numbers of mast cells.
22 . The method of claim 16 wherein the mammal has elevated levels of neurokinin in the urine.
23 . The method of claim 16 wherein the mammal is post-transurethral resection.
24 . The method of claim 1 wherein the TLR agonist is formulated as a salt of an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethane disulfonic acid, oxalic acid and isethionic acid.
25 . The method of claim 16 wherein the TLR agonist is formulated as a salt of an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethane disulfonic acid, oxalic acid and isethionic acid.