Drug – bio-affecting and body treating compositions – Solid synthetic organic polymer as designated organic active... – Aftertreated polymer
Reexamination Certificate
1996-12-30
2001-03-20
Webman, Edward J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Solid synthetic organic polymer as designated organic active...
Aftertreated polymer
C424S078350, C514S824000
Reexamination Certificate
active
06203785
ABSTRACT:
BACKGROUND OF THE INVENTION
Salts of bile acids act as detergents to solubilize and, consequently, aid in the digestion of, dietary fats. Bile acids are derived from cholesterol. Following digestion, bile acids can be passively absorbed in the jejunum or reabsorbed by active transport in the ileum. Bile acids which are not reabsorbed are deconjugated and dehydroxylated by bacterial action in the distal ileum and large intestine.
Reabsorption of bile acids from the intestine conserves lipoprotein cholesterol in the bloodstream. Conversely, the blood cholesterol level can be reduced by hindering reabsorption of bile acids.
One method of reducing the amount of bile acids that are reabsorbed is oral administration of compounds that sequester the bile acids and cannot themselves be absorbed. The sequestered bile acids consequently are excreted. Serum cholesterol is then employed to produce more bile acids, thereby lowering the serum cholesterol level of the patient.
SUMMARY OF THE INVENTION
The present invention relates to a method for removing bile acids from a patient as well as certain polymers for use in the method. The method comprises the step of administering to the patient a therapeutically effective amount of a polymer characterized by a diallylamine monomer wherein the amino nitrogen atom bears at least one hydrophobic substituent. The hydrophobic substituent can be a substituted or unsubstituted, straight chain or branched C
3
-C
24
-alkyl group, a substituted or unsubstituted arylalkyl group or a substituted or unsubstituted aryl group. The polymer to be administered can be hoinopolymer or a copolymer.
In one embodiment, the polymer to be administered is a crosslinked or linear poly(diallylamine) polymer wherein at least 10% of the amino nitrogen atoms are substituted by a C
3
-C
24
-alkyl group. In another embodiment, the polymer to be administered is characterized by a diallylamine monomer wherein the amino nitrogen atom bears an alkyl group which is substituted with a quaternary ammonium group. The nitrogen atom of the ammonium group can bear at least one terminal hydrophobic substituent.
The polymer to be administered can comprise secondary amino groups, tertiary amino groups or quaternary ammonium groups or a combination thereof. Polymers which comprise secondary or tertiary amino groups can also be administered in the form of salts of a pharmaceutically acceptable acid.
The polymer can be linear or crosslinked. In one embodiment, the polymer is crosslinked via the incorporation of a multifunctional comonomer. In another embodiment, the polymer is crosslinked via bridging groups which link amino nitrogen atoms on different polymer strands.
In another embodiment, the invention relates to poly(diallylamine) polymers which are useful as bile acid sequestrants. These polymers are characterized by an diallylamine monomer, or repeat unit, wherein the amino nitrogen bears an alkyl substituent which is substituted with an ammonium group. The polymer can be a homopolymer or a copolymer.
The present invention offers the advantage that both substituted and unsubstituted diallylamines are readily polymerized and crosslinked, in comparison to other amine monomers. Such polymers also provide improved efficacy over polymers utilized in prior art methods.
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Dhal Pradeep K.
Holmes-Farley Stephen Randall
Petersen John S.
GelTex Pharmaceuticals Inc.
Hamilton Brook Smith & Reynolds P.C.
Webman Edward J.
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