Claims
- 1. A method of treating dyslipidemia or a disease associated with dyslipidemia, comprising administering to a subject an apolipoprotein-sphingomyelin complex comprising apolipoprotein and sphingomyelin in an amount effective to achieve a serum level of free or complexed apolipoprotein in the range of 10 mg/dL to 300 mg/dL above a baseline level before administration.
- 2. The method of claim 1 in which the disease associated with dyslipidemia is selected from the group consisting of coronary heart disease; coronary artery disease; cardiovascular disease, hypertension, restenosis, vascular or perivascular diseases; dyslipidemic disorders; dyslipoproteinemia; high levels of low density lipoprotein cholesterol; high levels of very low density lipoprotein cholesterol; low levels of high density lipoproteins; high levels of lipoprotein Lp(a) cholesterol; high levels of apolipoprotein B; atherosclerosis (including treatment and prevention of atherosclerosis); hyperlipidemia; hypercholesterolemia; familial hypercholesterolemia (FH); familial combined hyperlipidemia (FCH); lipoprotein lipase deficiencies, such as hypertriglyceridemia, hypoalphalipoproteinemia, and hypercholesterolemialipoprotein.
- 3. The method of claim 1 in which the apolipoprotein is selected from the group consisting of preproapoliprotein, preproApoA-I, proApoA-I, ApoA-I, preproApoA-II, proApoA-II, ApoA-II, preproApoA-IV, proApoA-IV, ApoA-IV, ApoA-V, preproApoE, proApoE, ApoE, preproApoA-IMilano, proApoA-IMilano, ApoA-IMilano, preproApoA-IParis, proApoA-IParis, and ApoA-IParis.
- 4. The method of claim 3 in which the apolipoprotein is a homodimer.
- 5. The method of claim 3 in which the apolipoprotein is a heterodimer.
- 6. The method of claim 1 in which the ratio of SM:apolipoprotein of the complex is in the range of 1:1 to 200:1 (mole/mole).
- 7. The method of claim 1 in which the ratio of SM:apolipoprotein of the complex is in the range of 1:2 to 200:1 (mole/mole).
- 8. The method of claim 1 in which the ratio of SM:apolipoprotein of the complex is about 2:1 (wt/wt).
- 9. The method of claim 1 in which the complex-comprises apolipoprotein and sphingomyelin.
- 10. The method of claim 9 in which the complex further includes phosphatidylcholine.
- 11. The method of claim 10 in which the phosphatidylcholine is soybean phosphatidylcholine.
- 12. The method of claim 1 wherein from 50% to70% of the lipid content of the complex is sphingomyelin.
- 13. The method of claim 1 wherein from 30-50% of the lipid content of the complex is phosphatidylcholine.
- 14. The method of claim 1 wherein the range of 10 mg/dL to 300 mg/dL is achieved between 5 minutes and 1 day after administration.
- 15. The method of claim 1 in which the apolipoprotein-sphingomyelin complex is administered at a periodic interval in an amount of about 40 mg to 2 g per person per administration.
- 16. The method of claim 15 in which administration is intravenous administration.
- 17. The method of claim 15 in which the periodic interval is about every 3 to 15 days.
- 18. The method of claim 15 in which the periodic interval is about every 5 to 10 days.
- 19. The method of claim 15 in which the periodic interval is about every 10 days.
- 20. The method of claim 15 in which the periodic interval is several times per day, wherein the dose does not reach a daily toxic dose.
- 21. The method of claim 15 in which administration is by slow infusion with a duration of more than one hour.
- 22. The method of claim 15 in which administration is by rapid infusion of one hour or less.
- 23. The method of claim 15 in which administration is by a single bolus injection.
- 24. The method of claim 1 in which the complex is co-administered with bile-acid resins, niacin, statins or fibrates.
- 25. A method of treating a disease associated with dyslipidemia, comprising administering to a subject an apolipoprotein-sphingomyelin complex in an amount effective to achieve a circulating plasma concentrations of a HDL-cholesterol fraction between 10% and 1000% of the initial HDL-cholesterol fraction concentration before administration.
- 26. The method of claim 25 in which the disease associated with dyslipidemia is selected from the group consisting of coronary heart disease; coronary artery disease; cardiovascular disease, hypertension, restenosis, vascular or perivascular diseases; dyslipidemic disorders; dyslipoproteinemia; high levels of low density lipoprotein cholesterol; high levels of very low density lipoprotein cholesterol; low levels of high density lipoproteins; high levels of lipoprotein Lp(a) cholesterol; high levels of apolipoprotein B; atherosclerosis (including treatment and prevention of atherosclerosis); hyperlipidemia; hypercholesterolemia; familial hypercholesterolemia (FH); familial combined hyperlipidemia (FCH); lipoprotein lipase deficiencies, such as hypertriglyceridemia, hypoalphalipoproteinemia, and hypercholesterolemialipoprotein.
- 27. The method of claim 25 in which the apolipoprotein is selected from the group consisting of preproapoliprotein, preproApoA-I, proApoA-I, ApoA-I, preproApoA-II, proApoA-II, ApoA-II, preproApoA-IV, proApoA-IV, ApoA-IV, ApoA-V, preproApoE, proApoE, ApoE, preproApoA-IMilano, proApoA-IMilano, ApoA-IMilano, preproApoA-IParis, proApoA-IParis, and ApoA-IParis.
- 28. The method of claim 27 in which the apolipoprotein is a homodimer.
- 29. The method of claim 27 in which the apolipoprotein is a heterodimer.
- 30. The method of claim 25 in which the ratio of SM:apolipoprotein of the complex is in the range of 1:1 to 200:1 (mole/mole).
- 31. The method of claim 25 in which the ratio of SM:apolipoprotein of the complex is in the range of 1:2 to 200:1 (mole/mole).
- 32. The method of claim 25 in which the ratio of SM:apolipoprotein of the complex is about 1:2 (wt/wt).
- 33. The method of claim 25 wherein the circulating plasma concentration of the HDL-cholesterol fraction is achieved between 5 minutes and 1 day after administration.
- 34. The method of claim 25 in which the complex comprises apolipoprotein and sphingomyelin.
- 35. The method of claim 34 in which the complex further includes phosphatidylcholine.
- 36. The method of claim 35 in which the phosphatidylcholine is soybean phosphatidylcholine.
- 37. The method of claim 25 wherein from 50% to70% of the lipid content of the complex is sphingomyelin.
- 38. The method of claim 25 wherein from 30-50% of the lipid content of the complex is phosphatidylcholine.
- 39. The method of claim 25 in which the apolipoprotein-sphingomyelin complex is administered at a periodic interval in an amount of about 40 mg to 2 g per person per administration.
- 40. The method of claim 39 in which administration is intravenous administration.
- 41. The method of claim 39 in which the periodic interval is about every 3 to 15 days.
- 42. The method of claim 39 in which the periodic interval is about every 5 to 10 days.
- 43. The method of claim 39 in which the periodic interval is about every 10 days.
- 44. The method of claim 39 in which the periodic interval is several times per day, wherein the dose does not reach a daily toxic dose.
- 45. The method of claim 39 in which administration is by slow infusion with a duration of more than one hour.
- 46. The method of claim 39 in which administration is by rapid infusion of one hour or less.
- 47. The method of claim 39 in which administration is by a single bolus injection.
- 48. The method of claim 39 in which the complex is co-administered with bile-acid resins, niacin, statins, or fibrates.
- 49. A method of treating dyslipidemia or a disease associated with dyslipidemia, comprising administering to a subject an apolipoprotein-sphingomyelin complex in an amount effective to achieve a circulating plasma concentration of a HDL-cholesterol fraction between 30 and 300 mg/dL.
- 50. A method of treating dyslipidemia or a disease associated with dyslipidemia, comprising administering to a subject an apolipoprotein-sphingomyelin complex in an amount effective to achieve a circulating plasma concentration of cholesteryl esters between 30 and 300 mg/dL.
- 51. The method of claim 49 wherein the circulating plasma concentration of the HDL-cholesterol fraction is achieved between 5 minutes and 1 day after administration.
- 52. The method of claim 49 wherein the circulating plasma concentration of cholesteryl esters is achieved between 5 minutes and 1 day after administration.
Parent Case Info
[0001] This application claims priority to U.S. Provisional Application Serial Number 60/381,512, filed May 17, 2002, incorporated herein by reference in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60381512 |
May 2002 |
US |