CROSSLINKED POLY (ALLYLAMINE) POLYMER PHARMACEUTICAL COMPOSITIONS
Pharmaceutical compositions for and methods of treating an animal, including a human, and methods of preparing such compositions. The pharmaceutical compositions contain crosslinked amine polymers and may be used, for example, to treat diseases or other metabolic conditions in which removal of a target species from the gastrointestinal tract would provide physiological benefits.
1 . A crosslinked poly(allylamine) polymer wherein the crosslinked poly(allylamine) polymer is veverimer, and less than 1.0% of the total number of carbon atoms present in the crosslinked poly(allylamine) polymer are sp 2 allyl carbons.
2 . The crosslinked poly(allylamine) polymer of claim 1 wherein less than 0.9% of the total number of carbon atoms present in the crosslinked poly(allylamine) polymer are sp 2 allyl carbons.
3 . The crosslinked poly(allylamine) polymer of any preceding claim wherein less than 0.8% of the total number of carbon atoms present in the crosslinked poly(allylamine) polymer are sp 2 allyl carbons.
4 . The crosslinked poly(allylamine) polymer of any preceding claim wherein less than 0.7% of the total number of carbon atoms present in the crosslinked poly(allylamine) polymer are sp 2 allyl carbons.
5 . The crosslinked poly(allylamine) polymer of any preceding claim wherein less than 0.6% of the total number of carbon atoms present in the crosslinked poly(allylamine) polymer are sp 2 allyl carbons.
6 . The crosslinked poly(allylamine) polymer of any preceding claim wherein more than 0.3% of the total number of carbon atoms present in the crosslinked poly(allylamine) polymer are sp 2 allyl carbons.
7 . The crosslinked poly(allylamine) polymer of any preceding claim wherein the percentage of sp 2 allyl carbons can be determined by measuring the percentage of sp 2 allyl carbons in the crosslinked poly(allylamine) polymer.
8 . The crosslinked poly(allylamine) polymer of any one of claims 1-7 wherein the percentage of sp 2 allyl carbons can be determined by calculating the percentage of sp 2 allyl carbons in the crosslinked poly(allylamine) polymer from the percentage of sp 2 allyl carbons measured in the poly(allylamine) polymer that is crosslinked to make the crosslinked poly(allylamine) polymer.
9 . The crosslinked poly(allylamine) polymer of claim 8 wherein the percentage of sp 2 allyl carbons in the crosslinked poly(allylamine) polymer can be determined by multiplying the percentage of sp 2 allyl carbons in the poly(allylamine) polymer by the ratio of the carbon to nitrogen weight ratio of the poly(allylamine) polymer to the carbon to nitrogen weight ratio of the crosslinked poly(allylamine) polymer.
10 . The crosslinked poly(allylamine) polymer of claim 9 wherein the ratio of the carbon to nitrogen weight ratio of the poly(allylamine) polymer to the carbon to nitrogen weight ratio of the crosslinked poly(allylamine) polymer is about 0.9.
11 . The crosslinked poly(allylamine) polymer of claim 9 or claim 10 wherein the carbon to nitrogen weight ratio of the poly(allylamine) polymer and the carbon to nitrogen weight ratio of the crosslinked poly(allylamine) polymer may be determined by elemental analysis.
12 . The crosslinked poly(allylamine) polymer of any one of claims 1-7 wherein the percentage of sp 2 allyl carbons in the crosslinked poly(allylamine) polymer can be determined by 13 C NMR.
13 . The crosslinked poly(allylamine) polymer of any one of claims 8-11 wherein the percentage of sp 2 allyl carbons in the poly(allylamine) polymer can be determined by 13 C NMR.
14 . The crosslinked poly(allylamine) polymer of claim 12 or claim 13 wherein the integration of the sp 2 allyl carbon peaks between 110-150 ppm and alkyl carbon peaks between 0-80 ppm is used to quantitate the percentage of sp 2 allyl carbons using the formula
%
sp
2
allyl
carbons
=
peak
integrations
(
110
-
150
ppm
)
peak
integration
(
0
-
80
ppm
)
+
peak
integration
(
110
-
150
ppm
)
×
100.
15 . The crosslinked poly(allylamine) polymer of any one of claims 12-14 wherein the 13 C NMR is quantitative 13 C solid state magic angle spinning (MAS) NMR.
16 . The crosslinked poly(allylamine) polymer of any one of claims 12-14 wherein the 13 C NMR is quantitative 13 C solid state cross-polarization magic angle spinning (CPMAS) NMR.
17 . The crosslinked poly(allylamine) polymer of any preceding claim wherein the crosslinked poly(allylamine) polymer contains less than 20 ppm allylamine (H 2 C═CHCH 2 NH 2 ) as an impurity.
18 . The crosslinked poly(allylamine) polymer of claim 17 wherein the allylamine content may be determined by the Cation IC Extraction Procedure.
19 . The crosslinked poly(allylamine) polymer of any preceding claim wherein when tested with the Heated Stability Assay (Stability Assay 2) the allylamine content of the crosslinked poly(allylamine) polymer increases by less than 2.5 ppm/day allylamine.
20 . The crosslinked poly(allylamine) polymer of any preceding claim wherein when tested with the Heated Stability Assay (Stability Assay 2) the allylamine content of the crosslinked poly(allylamine) polymer increases by less than 2.0 ppm/day allylamine.
21 . The crosslinked poly(allylamine) polymer of any preceding claim wherein when tested with the Heated Stability Assay (Stability Assay 2) the allylamine content of the crosslinked poly(allylamine) polymer increases by less than 1.5 ppm/day allylamine.
22 . The crosslinked poly(allylamine) polymer of any preceding claim for use in a method of treating metabolic acidosis.