Crosslinked polydiallymine copolymers for the treatment of type 2 diabetes

1. A polydiallylamine block copolymer comprising a plurality of polymer chains, wherein each polymer chain is according to Formula (I):

wherein:

u, and v are each independently an integer from 0 to 200,000; and

w is an integer from 1 to 200,000;

A, B, C and D are each independently repeat units selected from Formula (II) or Formula (III);

wherein Formula (II) is according to the structural formula:

or a pharmaceutically acceptable salt thereof, wherein:

m is 0 or 1;

n is an integer from 1 to 200,000;

and Formula (III) is according to the structural formula:

or a pharmaceutically acceptable salt thereof, wherein:

o is 0 or 1;

p is an integer from 1 to 200,000;

R 1 and R 2 and R 3 and R 4 are each independently selected from a group consisting of

H, (C 1 -C 10 )alkyl, (C 2 -C 9 )heteroalkyl, (C 3 -C 10 )cycloalkyl,

(C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl, (C 2 -C 9 )heteroaryl,

(C 1 -C 10 )alkylamine, —O(O)C—(C 1 -C 10 )alkyl, (C 1 -C 10 )alkyl-COOH,

(C 3 -C 10 )cycloalkyl-COOH, —(O)CH 3 , —OH, amide,

a guanidino group represented by Formula (A)

wherein a is an integer from 0 to 25,

a guanidinium chloride group represented by Formula (B),

wherein b is an integer from 0 to 25,

a guanidinobenzene group represented by Formula (C),

wherein c is an integer from 0 to 25,

a dihydroxy group, represented by Formula (D),

wherein d is an integer from 0 to 25,

a polyethylene glycol group, represented by Formula (E)

wherein e is an integer from 1 to 400,

a group represented by Formula (F)

wherein R z and R y are each independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 2 -C 9 )heteroalkyl,

(C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl,

(C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylamine, —O(O)C-(C 1 -C 10 )alkyl,

(C 1 -C 10 )alkyl-COOH, (C 3 -C 10 )cycloalkyl-COOH, —(O)CH 3 , —OH and

amide,

a group represented by Formula (G)

wherein R x and R w are each independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 2 -C 9 )heteroalkyl,

(C 3 -C 10 )cycloalkyl, (C 2 -C 9 )heterocycloalkyl, (C 6 -C 14 )aryl,

(C 2 -C 9 )heteroaryl, (C 1 -C 10 )alkylannine, —O(O)C—(C 1 -C 10 )alkyl,

(C 1 -C 10 )alkyl-COOH, (C 3 -C 10 )cycloalkyl-COOH, —(O)CH 3 , cyano, cyano(C 1 -C 10 )alkyl, —OH and

amide,

and a point of attachment to another repeat unit of the copolymer;

and wherein:

(a) each polymer chain must be cross-linked with at least one other polymer chain, and

(b) each polymer chain may be internally cross-linked; and

wherein the molar ratio of Formula (II) monomer:Formula (III) monomer in the polydiallylamine copolymer is from 99:1 to 1:99, and the ratio of cross-linked repeat units:un-cross-linked repeat units is from 1:99 to 50:50.

2. The copolymer according to claim 1 , wherein each m is 0.

3. The copolymer according to claim 1 , wherein each m is 0 and each o is 1.

4. The copolymer according to claim 1 , wherein the ratio of Formula (II) monomer:Formula (III) monomer is from 90:10 to 5:95.

5. The copolymer according to claim 1 , wherein the copolymers has been cross-linked with a cross-linking agent.

6. The copolymer according to claim 5 , wherein the cross-linking agent is selected from epichlorohydrin, epibromohydrin, (iodomethyl)oxirane, glycidyl tosylate, glycidyl 3-nitrobenzenesulfonate, 4-tosyloxy-1,2-epoxybutane, bromo-1,2-epoxybutane, 1,2-dibromoethane, 1-bromo-2-chloroethane, 1,3-dibromopropane, bis(2-chloroethyl)amine, tris(2-chloroethyl)amine, and bis(2-chloroethyl)methylamine, 1,3-butadiene diepoxide, 1,5-hexadiene diepoxide, diglycidyl ether, 1,2,7,8-diepoxyoctane, 1,2,9,10-diepoxydecane, ethylene glycol diglycidyl ether, propylene glycol diglycidyl ether, 1,4-butanediol diglycidyl ether, glycerol diglycidyl ether, 1,3-diglycidyl glyceryl ether, N,N-diglycidylaniline, neopentyl glycol diglycidyl ether, diethylene glycol diglycidyl ether, 1,4-bis(glycidyloxy)benzene, resorcinol digylcidyl ether, 1,6-hexanediol diglycidyl ether, trimethylolpropane diglycidyl ether, 1,4-cyclohexanedimethanol diglycidyl ether, 1,3-bis-(2,3-epoxypropyloxy)-2-(2,3-dihydroxypropyloxy)propane, 1,2-cyclohexanedicarboxylic acid diglycidyl ester, 2,2′-bis(glycidyloxy)diphenylmethane, bisphenol F diglycidyl ether, 1,4-bis(2′,3′-epoxypropyl)perfluoro-n-butane, 2,6-di(oxiran-2-ylmethyl)-1, 2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindol-1,3,5,7-tetraone, bisphenol A diglycidyl ether, ethyl 5-hydroxy-6,8-di(oxiran-2-ylmethyl)-4-oxo-4h-chromene-2-carbo xylate, bis[4-(2,3-epoxy-propylthio) phenyl]-sulfide, 1,3-bis(3-glycidoxypropyl)tetramethyldisiloxane, 9,9-bis[4-(glycidyloxy) phenyl]fluorene, triepoxyisocyanurate, glycerol triglycidyl ether, N,N-diglycidyl-4-glycidyloxyaniline, isocyanuric acid (S,S,S)-triglycidyl ester, isocyanuric acid (R,R,R)-triglycidyl ester, triglycidyl isocyanurate, trimethylolpropane triglycidyl ether, glycerol propoxylate triglycidyl ether, triphenylolmethane triglycidyl ether, 3,7,14-tris[[3-(epoxypropoxy)propyl]dimethylsilyloxy]-1, 3,5,7,9,11,14-heptacyclopentyltricyclo[7.3.3.15,11]heptasiloxane, 4,4′-methylenebis(N, N-diglycidylaniline), bis(halomethyl)benzene, bis(halomethyl)biphenyl and bis(halomethyl)naphthalene.

7. The copolymer according to claim 6 , wherein the cross-linking agent is epichlorohydrin.