Method for removing phosphate and polymer used therefore
AssigneeGenzyme Corporation
InventorsChad C. Huval, Stephen Randall Holmes-Farley, Pradeep K. Dhal
Life of this patent
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Abstract
Polymers and compositions utilizing such polymers are disclosed for treating hyperphosphatemia and other illnesses associated with elevated serum phosphate levels. Phosphate binding polymers, or a pharmaceutically acceptable salt of the polymers, comprise pendent groups extending from a backbone of the polymer. Each pendent group comprises at least two nitrogen-bearing functional groups which bind phosphate. Variations of such polymer and compositions are disclosed.
Claims18
A polymer comprising pendent groups extending from a backbone, each pendent group comprising at least three nitrogen bearing functional groups, at least two of the nitrogen bearing functional groups which bind phosphate, wherein each pendent group is represented by Structural Formula (I):
- wherein:
- each amine in Structural Formula (I) is independently optionally quaternarized with R;
- each R is independently hydrogen or an optionally substituted alkyl group;
- T0 is a covalent bond, carbonyl, —Ar—, -T1-, —Ar-T1-, —O-T2-, —S-T2-, —C(O)-T1-, —C(O)O-T2-, —C(O)S-T1-, or —C(O)N(RT)-T2-, wherein RT is hydrogen or an optionally substituted C1-C3 alkyl group;
- Ar is an optionally substituted arylene group;
- T1 is an optionally substituted C1-5 alkylene group optionally interrupted by an optionally substituted arylene group;
- T2 is an optionally substituted C2-5 alkylene group;
- and
- a) NR6R7 taken together is
- 1) a monocycle non-aromatic ring substituted with two or more groups selected from amine, ammonium, amino alkyl, and ammonium alkyl,
- or
- 2) a bridge bicycle non-aromatic ring comprising at least two ring amine or ammonium groups;
- or
- b) R6 is hydrogen, an optionally substituted alkyl group, or an optionally substituted aryl group, and
- R7 is
- 1) represented by Structural Formula (Ia)
- if T0 is O -T2, S-T2, Ar, or Ar-T1;
- and
- represented by Structural Formula (Ib)
- if T0 is a covalent bond, carbonyl, -T1-, —C(O)-T1, C(O)O-T2-, —C(O)S-T1, or —C(O)N(RT)-T2-;
- where
- X is
- (A) C-Rx, where Rx is hydrogen, an optionally substituted alkyl group, or an optionally substituted aryl group, or
- (B) N or N+(R),
- Y is
- (A) a covalent bond or an optionally substituted C1-C10 alkylene group optionally interrupted by an optionally substituted arylene group, if X is C—Rx, and
- (B) an optionally substituted C2-C10 alkylene group optionally interrupted by an optionally substituted arylene group, if X is N or N+(R),
- R9 is
- (A) an alkyl group or an aryl group, the group substituted with at least one group selected from amine, ammonium, amino alkyl, and ammonium alkyl, if X is C—Rx, and
- (B) hydrogen, an optionally substituted alkyl group, or an optionally substituted aryl group, if X is N or W(R),
- R10 is hydrogen, an optionally substituted alkyl group, or an optionally substituted aryl group, and
- R12 and R13 are each independently an alkyl group terminally substituted with amine or ammonium, or
- 2) -Y1-Cy,
- where Y1 is a covalent bond or an optionally substituted C1-C5 alkylene group, and Cy is a monocyclic non-aromatic ring substituted with two or more groups selected from amine, ammonium, amino alkyl, and ammonium alkyl,
- wherein the polymer is not one of
- poly(tris(2-aminoethyl)amine-acrylamide) and
- polyepichlorohydrin/tris(2-aminoethyl)amine,
- wherein the polymer comprises no nitrogen in the polymer backbone, and wherein the polymer comprises no vicinal diamine, vicinal diammonium, vicinal diaminoalkyl or vicinal diammoniumalkyl groups in the polymer backbone;
- provided that if the polymer comprises a repeat unit represented by any one of
- Structural Formulas (A)-(G):
- wherein
- A is either a covalent bond, C(O), or CH2;
- R1 is an alkyl amine or alkyl ammonium group;
- R1A is a polyleneimine;
- R2 and R3 are each independently hydrogen, an alkyl group, an alkyl amino group, or an aryl group;
- R4 is an alkyl ammonium group;
- and
- R5 is hydrogen, or an optionally substituted alkyl group, or an optionally substituted aryl group;
- then the polymer comprises a second repeat unit with a multifunctional phosphate binding pendent group, wherein said second repeat unit is not represented by Structural Formulas (A)-(G).
A polymer comprising a repeat unit represented by one of Structural Formulas (VII) and (VIII):
- wherein:
- each amine in Structural Formulas (VII) and (VIII) is independently optionally quaternarized with R;
- each R is independently hydrogen or an optionally substituted alkyl group;
- R8 Is hydrogen or methyl;
- each R17 is independently hydrogen or an optionally substituted C1-C5 alkyl;
- Ar is an optionally substituted arylene group;
- each To is independently a covalent bond, carbonyl, —Ar—, —Ar-T1-, -T1-, —O-T2-,
- —S-T2-, —C(O)-T1-, —C(O)O-T2-, —C(O)S-T1-, or —C(O)N(RT)-T2-,
- wherein RT is hydrogen or an optionally substituted C1-C3 alkyl group;
- T1 is an optionally substituted C1-C5 alkylene group optionally interrupted by an optionally substituted arylene group;
- T2 is an optionally substituted C2-C5 alkylene group;
- X is C-Rx, N, or N+ (R), where Rx is hydrogen or an optionally substituted alkyl group;
- and
- each Y2 is independently
- (i) optionally substituted C2-5S alkylene when X is N or N+(R),
- and
- (ii) optionally substituted C1-C5 alkylene when X is C-Rx.
Dependencies are inferred from the claim text.