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Details for Patent: 5,618,530

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Details for Patent: 5,618,530

Title: Hydrophobic amine polymer sequestrant and method of cholesterol depletion
Abstract:An amine polymer includes a substituent bound to an amine of the polymer. The substituent includes a quaternary amine-containing moiety having at least one hydrophobic moiety. A method for binding bile salts of bile acids in a mammal includes orally administering to the mammal a therapeutically-effective amount of the amine polymer.
Inventor(s): Mandeville, III; W. Harry (Lynnfield, MA), Holmes-Farley; Stephen R. (Arlington, MA), Petersen; John S. (Acton, MA)
Assignee: GelTex Pharmaceuticals, Inc. (Waltham, MA)
Filing Date:Jun 06, 1995
Application Number:08/469,659
Claims:1. A method for binding bile salts in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of a hydrocarbon amine polymer having a substituent bound to an amine of the hydrocarbon amine polymer, the substituent including a quaternary amine-containing moiety that is bound to said amine of the hydrocarbon amine polymer by an alkylene linking group having three or more carbons, said quarternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons.

2. The method of claim 1, wherein said orally-administered hydrocarbon amine polymer is crosslinked by a crosslinking moiety.

3. The method of claim 2, wherein said orally-administered hydrocarbon amine polymer is formed by a method that includes crosslinking the hydrocarbon amine polymer by said crosslinking moiety and subsequently adding the substituent, said substituent including a quaternary amine-containing moiety, to said hydrocarbon amine polymer.

4. The method of claim 3, wherein said crosslinking moiety is present in an amount in a range of between about 0.5 and about twenty percent of amines of the orally-administered hydrocarbon amine polymer.

5. The method of claim 4, wherein the crosslinking moiety is present in an amount in a range of between about 0.5 and about six percent of amines of the orally-administered hydrocarbon amine polymer.

6. The method of claim 4, wherein said terminal hydrophobic alkyl substituent includes a beryl group.

7. The method of claim 4, wherein said terminal hydrophobic alkyl substituent includes an octyl group.

8. The method of claim 4, wherein said terminal hydrophobic alkyl substituent includes a decyl group.

9. The method of claim 4, wherein said terminal hydrophobic alkyl substituent includes a dodecyl group.

10. A method for reducing blood cholesterol in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of a hydrocarbon amine polymer having a substituent bound to an amine of the hydrocarbon amine polymer, the substituent including a quaternary amine-containing moiety that is bound to said amine of the hydrocarbon amine polymer by an alkylene linking group having three or more carbons, said quaternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons.

11. A method for treating atherosclerosis in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of a hydrocarbon amine polymer having a substituent bound to an amine of the hydrocarbon amine polymer, the substituent including a quaternary amine-containing moiety that is bound to said amine of the hydrocarbon amine polymer by an alkylene linking group having three or more carbons, said quaternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons.

12. A method for treating hypercholesterolemia in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of a hydrocarbon amine polymer having a substituent bound to an amine of the hydrocarbon amine polymer, the substituent including a quaternary amine-containing moiety that is bound to said amine of the hydrocarbon amine polymer by an alkylene linking group having three or more carbons, said quaternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons.

13. A method for binding bile salts in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of a poly(allylamine) polymer having a substituent bound to an amine of the poly(allylamine), the substituent including a quaternary amine-containing moiety that is bound to said amine of the poly(allylamine) by an alkylene linking group having three or more carbons, said quaternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons.

14. A method for reducing blood cholesterol in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of a poly(allylamine) polymer having a substituent bound to an amine of the poly(allylamine), the substituent including a quaternary amine-containing moiety that is bound to said amine of the poly(allylamine) by an alkylene linking group having three or more carbons, said quaternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons.

15. A method for treating atherosclerosis in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of a poly(allylamine) polymer having a substituent bound to an amine of the poly(allylamine), the substituent including a quaternary amine-containing moiety that is bound to said amine of the poly(allylamine) by an alkylene linking group having three or more carbons, said quaternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons.

16. A method for treating hypercholesterolemia in a mammal, comprising the step of orally administering to the mammal a therapeutic amount of a poly(allylamine) polymer having a substituent bound to an amine of the poly(allylamine), the substituent including a quaternary amine-containing moiety that is bound to said amine of the poly(allylamine) by an alkylene linking group having three or more carbons, said quaternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons.

17. A method for reducing plasma lipid content of a mammal, comprising the step of orally administering to the mammal a therapeutically effective amount of a hydrocarbon amine polymer, comprising a substituent bound to an amine of the hydrocarbon amine polymer, the substituent including a quaternary amine-containing moiety that is bound to said amine of the hydrocarbon amine polymer by an alkylen linking group having three or more carbons, said quaternary amine-containing moiety also including at least one terminal hydrophobic alkyl substituent, having between about 6 and 20 carbons that sequesters with high affinity conjugated primary bile acids including conjugated cholic acid and conjugated chenodeoxycholic acid secreted by said mammal, whereby a substantial portion of said conjugated primary bile acids are excreted by the mammal, thereby causing accelerated lipid metabolism and consequent lowering of plasma lipid content of said mammal.
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