Claims
- 1. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound, the therapeutic compound comprising at least one anionic group attached to a carrier molecule, or a pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.
- 2. The method of claim 1 further comprising administering the therapeutic compound in a pharmaceutically acceptable vehicle.
- 3. The method of claim 1, wherein the carrier molecule is selected from the group consisting of a carbohydrate, a polymer, a peptide, a peptide derivative, an aliphatic group, an alicyclic group, a heterocyclic group, an aromatic group and combinations thereof.
- 4. The method of claim 1, wherein the anionic group is selected from the group consisting of a sulfonate group, a sulfate group, a carboxylate group, a phosphate group, a phosphonate group, and a heterocyclic group selected from the group consisting of
- 5. The method of claim 1, wherein the carrier molecule is selected for delivery of the therapeutic compound to the brain.
- 6. The method of claim 1, wherein the therapeutic compound is delivered liposomally.
- 7. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound, the therapeutic compound comprising at least one sulfonate group covalently attached to a carrier molecule, or a pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.
- 8. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound, the therapeutic compound having the following formula:
- 9. The method of claim 7, wherein the therapeutic compound is administered orally.
- 10. The method of claim 7, further comprising administering the therapeutic compound in a pharmaceutically acceptable vehicle.
- 11. The method of claim 7, wherein the carrier molecule is selected for delivery of the therapeutic compound to the brain.
- 12. The method of claim 7, wherein the therapeutic compound is delivered liposomally.
- 13. The method of claim 7, wherein the carrier molecule is selected from the group consisting of a carbohydrate, a polymer, a peptide, a peptide derivative, an aliphatic group, an alicyclic group, a heterocyclic group, an aromatic group and combinations thereof.
- 14. The method of claim 13, wherein the carrier molecule is a carbohydrate.
- 15. The method of claim 13, wherein the carrier molecule is a lower aliphatic group.
- 16. The method of claim 13, wherein the carrier molecule is a polymer.
- 17. The method of claim 16, wherein the polymer is selected from the group consisting of substituted and unsubstituted vinyl, acryl, styrene and carbohydrate-derived polymers and copolymers and pharmaceutically acceptable salts thereof.
- 18. The method of claim 13, wherein the carrier molecule includes a heterocylic group.
- 19. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound, the therapeutic compound comprising at least one sulfonate group covalently attached to a carrier molecule, or a pharmaceutically acceptable salt thereof.
- 20. The method of claim 19 further comprising administering the therapeutic compound in a pharmaceutically acceptable vehicle.
- 21. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound, the therapeutic compound comprising at least one sulfate group covalently attached to a carrier molecule, or a pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.
- 22. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound, the therapeutic compound having the following formula:
- 23. The method of claim 21, wherein the therapeutic compound is administered orally.
- 24. The method of claim 21, further comprising administering the therapeutic compound in a pharmaceutically acceptable vehicle.
- 25. The method of claim 21, wherein the carrier molecule is selected from the group consisting of a carbohydrate, a polymer, a peptide, a peptide derivative, an aliphatic group, an alicyclic group, a heterocyclic group, an aromatic group and combinations thereof.
- 26. The method of claim 25, wherein the carrier molecule is a carbohydrate.
- 27. The method of claim 25, wherein the carrier molecule is a lower aliphatic group.
- 28. The method of claim 25, wherein the carrier molecule is a polymer.
- 29. The method of claim 28, wherein the polymer is selected from the group consisting of substituted and unsubstituted vinyl, acryl, styrene and carbohydrate-derived polymers and copolymers and pharmaceutically acceptable salts thereof.
- 30. The method of claim 25, wherein the carrier molecule includes a heterocyclic group.
- 31. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfonate group covalently attached to a lower aliphatic group, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 32. The method of claim 31, wherein the therapeutic compound is selected from the group consisting of ethanesulfonic acid, 1,2-ethanedisulfonic acid, 1-propanesulfonic acid, 1,3-propanedisulfonic acid, 1,4-butanedisulfonic acid, 1,5-pentanedisulfonic acid, 2-aminoethanesulfonic acid, 4-hydroxybutane-1-sulfonic acid, and pharmaceutically acceptable salts thereof.
- 33. The method of claim 31, wherein the therapeutic compound is administered orally.
- 34. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfonate group covalently attached to a disaccharide, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 35. The method of claim 34, wherein the disaccharide is sucrose.
- 36. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfonate group covalently attached to a polymer, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 37. The method of claim 36, wherein the therapeutic compound is selected from the group consisting of poly(2-acrylamido-2-methyl-1-propanesulfonic acid); poly(2-acrylamido-2-methyl-1-propanesulfonic acid-co-acrylonitrile); poly(2-acrylamido-2-methyl-1-propanesulfonic acid-co-styrene); poly(vinylsulfonic acid); poly(sodium 4-styrenesulfonic acid); a sulfonate derivative of poly(acrylic acid); a sulfonate derivative of poly(methyl acrylate); a sulfonate derivative of poly(methyl methacrylate); and pharmaceutically acceptable salts thereof.
- 38. The method of claim 37, wherein the therapeutic compound is poly(vinylsulfonic acid) or a pharmaceutically acceptable salt thereof.
- 39. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfonate group covalently attached to carrier molecule that includes a heterocyclic group, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 40. The method of claim 39, wherein the compound is selected from the group consisting of 3-(N-morpholino)propanesulfonic acid, tetrahydrothiophene-1,1-dioxide-3,4-disulfonic acid, and pharmaceutically acceptable salts thereof.
- 41. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfonate group covalently attached to a peptide and a peptide derivative, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 42. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfate group covalently attached to a lower aliphatic group, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 43. The method of claim 42, wherein the therapeutic compound is selected from the group consisting of ethyl sulfuric acid, 1,2-ethanediol disulfuric acid, 1-propyl sulfuric acid, 1,3-propanediol disulfuric acid, 1,4-butanediol disulfuric acid, 1,5-pentanediol disulfuric acid, 2-amino-ethanesulfuric acid, 1,4-butanediol monosulfuric acid, and pharmaceutically acceptable salts thereof.
- 44. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfate group covalently attached to a disaccharide, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 45. The method of claim 44, wherein the therapeutic compound is sucrose octasulfate or a pharmaceutically acceptable salt thereof.
- 46. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfate group covalently attached to a polymer, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 47. The method of claim 46, wherein the therapeutic compound is selected from the group consisting of poly(2-acrylamido-2-methyl-1-propanesulfuric acid); poly(2-acrylamido-2-methyl-1-propanesulfuric acid-co-acrylonitrile); poly(2-acrylamido-2-methyl-1-propanesulfuric acid-co-styrene); poly(vinylsulfuric acid); poly(sodium 4-styrenesulfuric acid); a sulfate derivative of poly(acrylic acid); a sulfate derivative of poly(methyl acrylate); a sulfate derivative of poly(methyl methacrylate); and pharmaceutically acceptable salts thereof.
- 48. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfate group covalently attached to a carrier molecule that includes a heterocyclic group, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 49. The method of claim 48, wherein the compound is selected from the group consisting of 3-(N-morpholino)propanesulfuric acid, tetrahydrothiophene-1,1-dioxide-3,4-diol disulfuric acid, and pharmaceutically acceptable salts thereof.
- 50. A method of inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound comprising at least one sulfate group covalently attached to a peptide and a peptide derivative, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable vehicle.
- 51. A pharmaceutical composition for treating amyloidosis comprising a therapeutic compound comprising at least one sulfonate group covalently attached to a carrier molecule, or a pharmaceutically acceptable salt thereof, in an amount sufficient to inhibit amyloid deposition in a subject, and a pharmaceutically acceptable vehicle.
- 52. The pharmaceutical composition of claim 51, wherein the carrier molecule is selected from the group consisting of a carbohydrate, a polymer, a peptide, a peptide derivative, an aliphatic group, an alicyclic group, a heterocyclic group, an aromatic group and combinations thereof.
- 53. The pharmaceutical composition of claim 51, wherein the therapeutic compound is poly(vinylsulfonic acid) or a pharmaceutically acceptable salt thereof.
- 54. The pharmaceutical composition of claim 51, wherein the therapeutic compound is selected from the group consisting of ethanesulfonic acid, 1,2-ethanedisulfonic acid, 1-propanesulfonic acid, 1,3-propanedisulfonic acid, 1,4-butanedisulfonic acid, 1,5-pentanedisulfonic acid, 2-amino-ethanesulfonic acid, 4-hydroxybutane-1-sulfonic acid, and pharmaceutically acceptable salts thereof.
- 55. The pharmaceutical composition of claim 51, wherein the therapeutic compound is selected from the group consisting of 3-(N-morpholino)propanesulfonic acid, tetrahydrothiophene-1,1-dioxide-3,4-disulfonic acid, and pharmaceutically acceptable salts thereof.
- 56. A pharmaceutical composition for treating amyloidosis comprising a therapeutic compound comprising at least one sulfate group covalently attached to a carrier molecule, or a pharmaceutically acceptable salt thereof, in an amount sufficient to inhibit amyloid deposition in a subject, and a pharmaceutically acceptable vehicle.
- 57. The pharmaceutical composition of claim 56, wherein the carrier molecule is selected from the group consisting of a carbohydrate, a polymer, a peptide, a peptide derivative, an aliphatic group, an alicyclic group, a heterocyclic group, an aromatic group and combinations thereof.
- 58. The pharmaceutical composition of claim 56, wherein the therapeutic compound is sucrose octasulfate or a pharmaceutically acceptable salt thereof.
- 59. The pharmaceutical composition of claim 56, wherein the therapeutic compound is selected from the group consisting of ethyl sulfuric acid, 1,2-ethanediol disulfuric acid, 1-propanesulfuric acid, 1,3-propanediol disulfuric acid, 1,4-butanediol disulfuric acid, 1,5-pentanediol disulfuric acid, 2-amino-ethanesulfuric acid, 1,4-butanediol monosulfuric acid, and pharmaceutically acceptable salts thereof.
- 60. The pharmaceutical composition of claim 51, wherein the therapeutic compound is encapsulated in a liposome.
- 61. The pharmaceutical composition of claim 56, wherein the therapeutic compound is encapsulated in a liposome.
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of application Ser. No. 08/403,230, filed Mar. 15, 1995, which is a continuation-in-part of application Ser. No. 08/315,391, filed Sep. 29, 1994, which is a continuation-in-part of application Ser. No. 08/219,798, filed Mar. 29, 1994, which is a continuation-in-part of application Ser. No. 08/037,844 filed Mar. 29, 1993, now abandoned, the contents of all of which are incorporated herein by reference.
Continuations (2)
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Number |
Date |
Country |
Parent |
09322577 |
May 1999 |
US |
Child |
09780233 |
Feb 2001 |
US |
Parent |
08463548 |
Jun 1995 |
US |
Child |
09322577 |
May 1999 |
US |
Continuation in Parts (4)
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Number |
Date |
Country |
Parent |
08403230 |
Mar 1995 |
US |
Child |
08463548 |
Jun 1995 |
US |
Parent |
08315391 |
Sep 1994 |
US |
Child |
08403230 |
Mar 1995 |
US |
Parent |
08219798 |
Mar 1994 |
US |
Child |
08315391 |
Sep 1994 |
US |
Parent |
08037844 |
Mar 1993 |
US |
Child |
08219798 |
Mar 1994 |
US |