초록

The present invention provides a pharmaceutical composition comprising a mixture of apolipoproteins. Methods for elevating HDL levels are also provided as are methods for the treatment and prevention of cardiovascular diseases and disorders, inflammation and metabolic diseases.

대표청구항 ▼

1. A pharmaceutical composition comprising a mixture of a human proapolipoprotein-4WF (SEQ ID NO: 3), and human mature apolipoprotein-4WF (SEQ ID NO: 4). 2. The pharmaceutical composition of claim 1, wherein the ratio of proapolipoprotein-4WF to corresponding apolipoprotein-4WF in the mixture ranges

1. A pharmaceutical composition comprising a mixture of a human proapolipoprotein-4WF (SEQ ID NO: 3), and human mature apolipoprotein-4WF (SEQ ID NO: 4). 2. The pharmaceutical composition of claim 1, wherein the ratio of proapolipoprotein-4WF to corresponding apolipoprotein-4WF in the mixture ranges from about 5:95 to about 95:5 (wt %). 3. The pharmaceutical composition of claim 2, wherein the ratio of proapolipoprotein-4WF to corresponding apolipoprotein-4WF in the mixture ranges from about 20:80 to about 80:20 (wt %). 4. The pharmaceutical composition of claim 3, wherein the ratio of proapolipoprotein-4WF to corresponding apolipoprotein-4WF in the mixture ranges from about 35:65 to about 65:35 (wt %). 5. The pharmaceutical composition of claim 4, wherein the ratio of proapolipoprotein-4WF to corresponding apolipoprotein-4WF in the mixture ranges from about 40:60 to about 60:40 (wt %). 6. The pharmaceutical composition of claim 4, wherein the ratio of proapolipoprotein-4WF to corresponding apolipoprotein-4WF in the mixture ranges from about 45:55 to about 55:45 (wt %). 7. The pharmaceutical composition of claim 6, wherein the ratio of proapolipoprotein-4WF to corresponding apolipoprotein-4WF in the mixture ranges from about 50:50 (wt %). 8. The pharmaceutical composition of claim 1, wherein the amount of mature apolipoprotein-4WF in the mixture is at least about 25 mg. 9. The pharmaceutical composition of claim 1, wherein the amount of mature apolipoprotein-4WF in the mixture is at least about 50 mg. 10. The pharmaceutical composition of claim 1, wherein the amount of mature apolipoprotein-4WF in the mixture is at least about 75 mg. 11. The pharmaceutical composition of claim 1, wherein the amount of mature apolipoprotein-4WF in the mixture is at least about 100 mg. 12. The pharmaceutical composition of claim 1, wherein the amount of mature apolipoprotein-4WF in the mixture is at least about 125 mg. 13. The pharmaceutical composition of claim 1, wherein the amount of mature apolipoprotein-4WF in the mixture is at least about 150 mg. 14. The pharmaceutical composition of claim 1, wherein the amount of mature apolipoprotein-4WF in the mixture is at least about 175 mg. 15. The pharmaceutical composition of claim 1, wherein the amount of mature apolipoprotein-4WF in the mixture is at least about 200 mg. 16. The pharmaceutical composition of claim 1, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is at least about 100 mg. 17. The pharmaceutical composition of claim 1, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is at least about 150 mg. 18. The pharmaceutical composition of claim 17, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is at least about 200 mg. 19. The pharmaceutical composition of claim 17, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is at least about 250 mg. 20. The pharmaceutical composition of claim 17, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is at least about 300 mg. 21. The pharmaceutical composition of claim 17, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is at least about 400 mg. 22. The pharmaceutical composition of claim 1, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF in the mixture ranges from about 25 mg to about 8,350 mg. 23. The pharmaceutical composition of claim 22, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF in the mixture ranges from about 25 mg to about 5,000 mg. 24. The pharmaceutical composition of 1, wherein the composition comprises a volume of about 0.5 mL to about 40 mL. 25. The pharmaceutical composition of claim 24, wherein the composition comprises a volume of about 1 mL to about 30 mL. 26. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient. 27. The pharmaceutical composition of claim 1, wherein the mature apolipoprotein-4WF is substantially free from a phospholipid, a triglyceride, a lipid, cholesterol, glycerol, a liposome, or combinations thereof. 28. The pharmaceutical composition of claim 1, wherein the mixture of proapolipoprotein-4WF and corresponding mature apolipoprotein-4WF is formulated with a pharmaceutically acceptable liquid excipient. 29. The pharmaceutical composition of claim 1, wherein the mixture of proapolipoprotein-4WF and corresponding mature apolipoprotein-4WF is soluble in 2.0 mL of liquid or less. 30. The pharmaceutical composition of claim 1, wherein the mixture of proapolipoprotein-4WF and corresponding mature apolipoprotein-4WF is soluble in 1.5 mL of liquid or less. 31. The pharmaceutical composition of claim 1, wherein the mixture of proapolipoprotein-4WF and corresponding mature apolipoprotein-4WF is soluble in 1.0 mL of liquid or less. 32. The pharmaceutical composition of claim 1, wherein the mixture comprises a ratio of proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF ranging from about 45:55 to about 55:45 (wt %), and the amount of mature apolipoprotein-4WF in the mixture ranges from about 25 mg to about 3,750 mg. 33. The pharmaceutical composition of claim 1, wherein the mixture comprises a ratio of proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF ranging from about 35:65 to about 65:35 (wt %), and the amount of mature apolipoprotein-4WF in the mixture ranges from about 25 mg to about 3,750 mg. 34. The pharmaceutical composition of claim 1, wherein the composition further comprises apolipoprotein-AI, apolipoprotein-AII, apolipoprotein-AIV apolipoprotein-AV, apolipoprotein-B, apolipoprotein-E, apolipoprotein AI-Milano, apolipoprotein AI-Paris, apolipoprotein AI-Marburg, or combinations thereof. 35. An injectable apolipoprotein composition comprising: a) mixture of human proapolipoprotein-4WF (SEQ ID NO: 3), and a corresponding human mature apolipoprotein-4WF (SEQ ID NO:4), and b) at least one pharmaceutically acceptable excipient. 36. The injectable apolipoprotein composition of claim 35, wherein the injectable composition is sterile. 37. The injectable apolipoprotein composition of claim 35, wherein the composition is chemically stable upon prolonged storage. 38. The injectable apolipoprotein composition of claim 35, wherein the composition is stable for at least about 72 hours. 39. The injectable apolipoprotein composition of claim 35, wherein the amount of the combined proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF in the mixture is about 25 mg to about 5,000 mg. 40. The injectable apolipoprotein composition of claim 35, wherein the ratio of proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF in the mixture ranges from about 5:95 to about 95:5 (wt %). 41. The injectable apolipoprotein composition of claim 35, wherein the ratio of proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF in the mixture ranges from about 20:80 to about 80:20 (wt %). 42. The injectable apolipoprotein composition of claim 35, wherein the ratio of proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF in the mixture ranges from about 35:65 to about 65:35 (wt %). 43. The injectable apolipoprotein composition of claim 35, wherein the ratio of proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF in the mixture ranges from about 40:60 to about 60:40 (wt %). 44. The injectable apolipoprotein composition of claim 35, wherein the ratio of proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF in the mixture ranges from about 45:55 to about 55:45 (wt %). 45. The injectable apolipoprotein composition of claim 35, wherein the ratio of proapolipoprotein-4WF to corresponding mature apolipoprotein-4WF in the mixture ranges from about 50:50 (wt %). 46. The injectable apolipoprotein composition of claim 35, wherein the amount of mature apolipoprotein-4WF in the mixture is at least 25 mg. 47. The injectable apolipoprotein composition of claim 35, wherein the amount of mature apolipoprotein-4WF in the mixture is at least 50 mg. 48. The injectable apolipoprotein composition of claim 35, wherein the amount of mature apolipoprotein-4WF in the mixture is at least 75 mg. 49. The injectable apolipoprotein composition of claim 35, wherein the amount of mature apolipoprotein-4WF in the mixture is at least 100 mg. 50. The injectable apolipoprotein composition of claim 35, wherein the amount of mature apolipoprotein-4WF in the mixture is at least 125 mg. 51. The injectable apolipoprotein composition of claim 35, wherein the amount of mature apolipoprotein-4WF in the mixture is at least 150 mg. 52. The injectable apolipoprotein composition of claim 35, wherein the amount of mature apolipoprotei-4WF in the mixture is at least 175 mg. 53. The injectable apolipoprotein composition of claim 35, wherein the amount of mature apolipoprotein-4WF in the mixture is at least 200 mg. 54. The injectable apolipoprotein composition of claim 35, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is from about 25 mg to about 5,000 mg. 55. The injectable apolipoprotein composition of claim 35, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is from about 100 mg to about 3,500 mg. 56. The injectable apolipoprotein composition of claim 35, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is from about 100 mg to about 2,750 mg. 57. The injectable apolipoprotein composition of claim 35, wherein the combined amount of pro apolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is from about 100 mg to about 2,000 mg. 58. The injectable apolipoprotein composition of claim 35, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is from about 100 mg to about 1,500 mg. 59. The injectable apolipoprotein composition of claim 35, wherein the combined amount of proapolipoprotein-4WF and the corresponding mature apolipoprotein-4WF is from about 700 mg to about 5,000 mg. 60. The injectable apolipoprotein composition of claim 35, comprising from about 25 mg to about 5,000 mg of the mixture of proapolipoprotein-4WF and corresponding mature apoliporotein-4WF, and from about 0.5 to about 30 mL of a suspending agent, wherein the ratio of proapolipoprotein-4WF to corresponding mature apoliporotein-4WF in the composition ranges from about 5:95 to 95:5 (wt %).