WO2006069240B1 - Composition and treatment methods for coronary artery disease - Google Patents

Composition and treatment methods for coronary artery disease

Info

Publication number
WO2006069240B1
WO2006069240B1 PCT/US2005/046591 US2005046591W WO2006069240B1 WO 2006069240 B1 WO2006069240 B1 WO 2006069240B1 US 2005046591 W US2005046591 W US 2005046591W WO 2006069240 B1 WO2006069240 B1 WO 2006069240B1
Authority
WO
WIPO (PCT)
Prior art keywords
phosphatidylcholine
lipid composition
plaque
subject
cholesterol
Prior art date
Application number
PCT/US2005/046591
Other languages
French (fr)
Other versions
WO2006069240A3 (en
WO2006069240A2 (en
Inventor
Byung-Hong Chung
Byung-Hui Cho
Original Assignee
Uab Research Foundation
Byung-Hong Chung
Byung-Hui Cho
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Uab Research Foundation, Byung-Hong Chung, Byung-Hui Cho filed Critical Uab Research Foundation
Priority to US11/722,664 priority Critical patent/US20080207503A1/en
Publication of WO2006069240A2 publication Critical patent/WO2006069240A2/en
Publication of WO2006069240A3 publication Critical patent/WO2006069240A3/en
Publication of WO2006069240B1 publication Critical patent/WO2006069240B1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1275—Lipoproteins; Chylomicrons; Artificial HDL, LDL, VLDL, protein-free species thereof; Precursors thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Abstract

The present disclosure demonstrates that cholesterol-free discoidal reconstituted HDL (R-HDL), phosphatidylcholine (PC) and PC liposomes effectively released cholesterol from ICP. Native HDL and its apolipoproteins were not able to release cholesterol from ICP. The release of ICP cholesterol by R-HDL was dose-dependent and accompanied by the transfer of >8x more PC in the reverse direction (i.e., from R-HDL to ICP), resulting in a marked enrichment of ICP with PC. The enrichment of ICP with PC resulted in the dissolution of cholesterol crystals on ICP and allowed the removal of ICP cholesterol by apo HDL and plasma. The present disclosure provides a method of treatment for removal of cholesterol from ICP in vivo and compositions for use in such method of treatment. Such methods may be used in the treatment and/or prevention of atherosclerosis, coronary artery disease, and related disease states and conditions.

Claims

AMENDED CLAIMS received by the International Bureau on 16 August 2006 (16.08.2006) What is claimed' original claims 1-33, replaced by claims 1-47.
1. A method for reducing the volume of a plaque in a subject, said method comprising the step of administering to said subject a therapeutically effective amount of a lipid composition comprising phosphatidylcholine, said phosphatidylcholine being dimyristoyl phosphatidylcholine or egg phosphatidylcholine, whereby at least a portion of said phosphatidylcholine is transferred from said lipid composition to said plaque.
2. A method for increasing the stability of a plaque in a subject, said method comprising the step of administering to said subject a therapeutically effective amount of a lipid composition comprising phosphatidylcholine, said phosphatidylcholine being dimyristoyl phosphatidylcholine or egg phosphatidylcholine, whereby at least a portion of said phosphatidylcholine is transferred from said lipid composition to said plaque.
3. A method of increasing the percentage of a phospholipid component in a plaque in a subject, said method comprising the step of administering to said subject a therapeutically effective amount of a lipid composition comprising phosphatidylcholine, said phosphatidylcholine being dimyristoyl phosphatidylcholine or egg phosphatidylcholine, whereby at least a portion of said phosphatidylcholine is transferred from said lipid composition to said plaque.
4. A method for enriching a plaque in a subject with phosphatidylcholine, said method comprising the step of administering to said subject a therapeutically effective amount of a lipid composition comprising phosphatidylcholine, said phosphatidylcholine being dimyristoyl phosphatidylcholine or egg phosphatidylcholine, whereby at least a portion of said phosphatidylcholine is transferred from said lipid composition to said plaque.
5. A method for decreasing a free cholesterol to phospholipid ratio in a plaque from a subject, said method comprising the step of administering to said subject a therapeutically effective amount of a lipid composition comprising phosphatidylcholine, said phosphatidylcholine being dimyristoyl phosphatidylcholine or egg phosphatidylcholine, whereby at least a portion of said phosphatidylcholine is transferred from said lipid composition to said plaque.
6. Cancelled.
7. Cancelled.
32
8. The method of any of claims 1-5 where said lipid composition further comprises a protein component.
9. The method of claim 9 where said protein component is an apolipoprotein.
10. The method of claim 10 where said apolipoprotein is apolipoprotein A 1.
11. The method of claim 10 where said apolipoprotein to phosphatidylcholine ration is from about 1 :1 to about 1 :8.
12. The method of any of claims 1-5 where said lipid composition is a high density lipoprotein.
13. Cancelled.
14. Cancelled.
15. The method of any of claims 1-5 where said lipid composition is a liposome.
16. Cancelled.
17. Cancelled.
18. The method of any of claims 1 -5 where said subject is a human.
19. A method for releasing cholesterol from a plaque in a subject, said method comprising the steps of administering to said subject a therapeutically effective amount of a lipid composition comprising phosphatidylcholine, said phosphatidylcholine being dimyristoyl phosphatidylcholine or egg phosphatidylcholine, whereby at least a portion of said phosphatidylcholine is transferred from said lipid composition to said plaque, and further administering to said subject a therapeutically effective amount of a cholesterol mobilizing agent whereby at least a portion of the cholesterol component of the plaque is transferred from said plaque to said cholesterol mobilizing agent.
20. The method of claim 19 where the cholesterol mobilizing agent is fresh plasma or a second lipid composition not comprising phosphatidylcholine.
21. The method of claim 19 where said second lipid composition comprises at least one protein.
22. The method of claim 21 where said at least one protein is an apolipoprotein.
23. The method of claim 22 where said apolipoprotein is apolipoprotein Al .
24. The method of claim 23 where said apolipoprotein to phospholipid ratio is from about 1 :1 to about 1 :8.
25. Cancelled.
26. Cancelled.
27. The method of any of claims 19-24 where said lipid composition is a high density lipoprotein.
28. Cancelled.
29. Cancelled.
30. The method of any of claims 19-24 where said lipid composition is a liposome.
31. Cancelled.
32. Cancelled.
33. The method of any of claims 19-24 where said subj ect is a human.
34. A method for releasing cholesterol from a plaque in a subject, said method comprising altering the lipid composition of said plaque in the subject by administering to said subject a therapeutically effective amount of a lipid composition comprising phosphatidylcholine, whereby at least a portion of said phosphatidylcholine is transferred from said lipid composition comprising phosphatidylcholine to said plaque, and further administering to said subject a therapeutically effective amount of a cholesterol mobilizing agent whereby at least a portion of the cholesterol component of the plaque is transferred from said plaque to said cholesterol mobilizing agent.
35. The method of claim 34 where said phosphatidylcholine is dimyristoyl phosphatidylcholine or egg phosphatidylcholine.
36. The method of claim 34 where the cholesterol mobilizing agent is fresh plasma or a second lipid composition not comprising phosphatidylcholine.
37. The method of claim 34 where said second lipid composition comprises at least one protein.
38. The method of claim 37 where said at least one protein is an apolipoprotein.
39. The method of claim 37 where said apolipoprotein is apolipoprotein Al .
40. The method of claim 39 where said apolipoprotein to phospholipid ratio is from about 1 :1 to about 1 :8.
41. A method for increasing the stability of a plaque in a subject or regressing said plaque said subject, said method comprising altering the lipid composition of said plaque in the subject by administering to said subject a therapeutically effective amount of a lipid composition, whereby at least a portion of said phosphatidylcholine is transferred from said lipid composition to said plaque.
42. The method of claim 41 where said phosphatidylcholine is dimyristoyl phosphatidylcholine or egg phosphatidylcholine.
43. The method of claim 41 where said lipid composition is a high density lipoprotein or a liposome.
44. The method of claim 41 where said lipid composition further comprises a protein component.
45. The method of claim 44 where said protein component is an apolipoprotein.
46. The method of claim 44 where said apolipoprotein is apolipoprotein Al .
35 7. The method of claim 46 where said apolipoprotein to phosphatidylcholine ration is from about 1 :1 to about 1:8.
36
PCT/US2005/046591 2004-12-22 2005-12-22 Composition and treatment methods for coronary artery disease WO2006069240A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/722,664 US20080207503A1 (en) 2005-06-22 2005-12-22 Composition and Treatment Methods for Coronary Artery Disease

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US63901104P 2004-12-22 2004-12-22
US60/639,011 2004-12-22

Publications (3)

Publication Number Publication Date
WO2006069240A2 WO2006069240A2 (en) 2006-06-29
WO2006069240A3 WO2006069240A3 (en) 2006-08-10
WO2006069240B1 true WO2006069240B1 (en) 2006-10-05

Family

ID=36602326

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/046591 WO2006069240A2 (en) 2004-12-22 2005-12-22 Composition and treatment methods for coronary artery disease

Country Status (1)

Country Link
WO (1) WO2006069240A2 (en)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5858399A (en) * 1992-04-09 1999-01-12 Northwestern University Acoustically reflective liposomes and methods to make and use the same
AU5561999A (en) * 1998-08-13 2000-03-06 Wistar Institute, The Methods for reducing atherosclerotic plaques
US6248728B1 (en) * 2000-03-10 2001-06-19 Kansas State University Research Foundation Phosphatidylcholine compositions and methods for lowering intestinal absorption and plasma levels of cholesterol
AU2001278864A1 (en) * 2000-06-30 2002-01-30 University Of Cincinnati Peptides with antioxidant and antimicrobial properties

Also Published As

Publication number Publication date
WO2006069240A3 (en) 2006-08-10
WO2006069240A2 (en) 2006-06-29

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