Polymers, compositions and methods for treating hyperuricemia
The disclosure provides small molecule compounds, polymers, and compositions thereof, as well as methods for preparing such polymers and compositions. Also provided is a method of using the polymers or compositions thereof for binding uric acid or precursor thereof, and/or for treating hyperuricemia, gout, and/or diseases caused by hyperuricemia.
1 . A grafted polytriallylamine comprising polytriallylamine, an anion, and a moiety that binds to uric acid or precursor thereof, wherein the moiety is linked to a tertiary amine of the polytriallylamine.
2 . The grafted polytriallylamine of claim 1 , wherein the moiety is selected from the group consisting of
a derivative thereof, and any combination thereof.
3 . The grafted polytriallylamine of claim 2 , wherein the moiety is
4 . The grafted polytriallylamine of claim 1 , wherein the anion is selected from the group consisting of Br − , Cl − , HCO 3 − and CO 3 2− .
5 . The grafted polytriallylamine of claim 1 , wherein the anion is HCO 3 − .
6 . The grafted polytriallylamine of claim 1 , wherein the grafted polytriallylamine is 4-N-(6-hexyl)-pyrimidine-2,4,6-triamine grafted polytriallylamine bicarbonate.
7 . The grafted polytriallylamine of claim 1 , wherein the grafted polytriallylamine is characterized by one or both of:
an average adsorption of uric acid of about 1.0 mmol/g; and
a glass transition temperature in a range of 85-95° C.
8 . The grafted polytriallylamine of claim 1 , wherein the mole percentage of the moiety to the tertiary amine is greater than 35% or in a range of 30% to 70%.
9 . The grafted polytriallylamine of claim 8 , wherein the mole percentage is about 50%.
10 . A pharmaceutical composition comprising
the grafted polytriallylamine of claim 1 ; and
a pharmaceutically acceptable excipient, diluent, or carrier.
11 . A method of treating a condition associated with an elevated serum uric acid level comprising administering to a subject in need thereof the pharmaceutical composition of claim 10 .
12 . The method of claim 11 , satisfying one or more of:
the grafted polytriallylamine binds to uric acid or precursor thereof;
said condition is hyperuricemia or gout; or
the pharmaceutical composition is administered orally.
13 . A method of treating a condition associated with an elevated serum uric acid level comprising administering to a subject in need thereof the grafted polytriallylamine of claim 1 .
14 . The method of claim 13 , satisfying one or more of:
the grafted polytriallylamine binds to uric acid or precursor thereof;
said condition is hyperuricemia or gout; or
the grafted polytriallylamine is administered orally.
15 . A method of making 4-N-(6-hexyl)-pyrimidine-2,4,6-triamine grafted polytriallylamine bicarbonate, comprising:
(1) polymerizing triallylamine to yield polytriallylamine; and
(2) reacting 4-N-(6-bromo-hexyl)-pyrimidine-2,4,6-triamine hydrobromide with the polytriallylamine at an elevated temperature.
16 . The method of claim 15 , wherein the polytriallylamine is synthesized according to a process comprising:
(1) adding triallylamine to concentrated HCl at a temperature less than 15° C. to prepare hydrochloride triallylamine in an aqueous solution; and
(2) mixing the hydrochloride triallylamine with 2,2′-Azobis(2-amidinopropane) dihydrochloride at an elevated temperature to yield polytriallylamine.
17 . The method of claim 16 , wherein the process satisfies one or more of the following conditions:
the pH of the aqueous solution in step (1) is in a range of 2.6 to 3.1;
the elevated temperature in step (2) is between 50° C. and 55° C.; or
the process further comprises:
(3) crushing the polytriallylamine into particles;
(4) dispersing the particles into a mixture comprising methanol and NaOH at room temperature to yield a dispersion; and
(5) filtering the dispersion to obtain a solid.
18 . The method of claim 15 , wherein the polytriallylamine is synthesized according to a process comprising:
(1) adding triallylamine to concentrated HCl at a temperature less than 15° C. to prepare hydrochloride triallylamine in an aqueous solution;
(2) mixing the hydrochloride triallylamine with 2,2′-Azobis(2-amidinopropane) dihydrochloride to obtain an aqueous phase; and
(3) providing an organic phase to mix with the aqueous phase under nitrogen protection at an elevated temperature to yield polytriallylamine in a mixture.
19 . The method of claim 18 , wherein the process satisfies one or more of the following conditions:
the pH of the aqueous solution in step (1) is in a range of 2.6 to 3.1;
the elevated temperature in step (3) is between 55° C. and 65° C. or in a range of 80° C. and 85° C.;
the organic phase comprises toluene and sorbitan monostearate (Span60); or
the process further comprises: (4) filtering the mixture to obtain a solid of polytriallylamine.
20 . A method of making a grafted polytriallylamine, comprising reacting an analog of pyrimidine-2,4-diamine with polytriallylamine, wherein the analog is selected from the group consisting of: