Methods and apparatus for creating particle derivatives of HDL with reduced lipid content

• US 8,268,787 B2
• Filed: 08/31/2011
• Issued: 09/18/2012
• Est. Priority Date: 07/03/2003
• Status: Active Grant

• Current Assignee: HDL Therapeutics, LLC, Lipid Sciences, Inc.
• Original Assignee: HDL Therapeutics, LLC
• Inventors: Bellotti, Marc, Brewer, H. Bryan Jr., Akeefe, Hassibullah, Conner, Adam Paul, Perlman, Timothy Jon
• Primary Examiner(s): KAM, CHIH MIN
• Application Number:
  US13/222,287
• Publication Number:
  US 20110318423A1
• Time in Patent Office: 384 Days
• Field of Search: 514/21, 514/2, 514/12, 514/171, 530/350, 530/359
• US Class Current: 514/21
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 9/1275 Lipoproteins; Chylomicrons; Artificial HDL, LDL, VLDL, protein-free species thereof; Precursors thereof
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B01D 11/0492 Applications, solvents used
• CPC Class Codes: B01D 15/00 Separating processes involving the treatment of liquids with solid sorbents using liquid sorbents B01D11/00; ion exchange processes or materials, sorbent materials in general B01J, e.g. sorbents for chromatography B01J20/281; for investigating or analysing materials G01N30/00; Apparatus therefor
• CPC Class Codes: B01D 15/426 Specific type of solvent
• CPC Class Codes: C07K 14/775 Apolipopeptides
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

The present invention is directed to systems, apparatus and methods for creating derivatives of at least one form of HDL without substantially affecting LDL. These derivatives of HDL are particles with reduced lipid content, particularly reduced cholesterol content. These particles have the capacity to bind cholesterol and are administered to a patient to enhance cellular cholesterol efflux and reduce cholesterol levels in cells, tissues, organs, and blood vessels. The present method is useful for treating atherogenic vascular disease and may be combined with other therapies such as statins, inhibitors of cholesterol absorption, niacin, anti-inflammatories, exercise and dietary restriction.

Claims

1. A method for enhancing cellular cholesterol efflux in a patient, comprising administering to the patient a composition comprising a particle derivative of at least one form of high density lipoprotein, wherein the particle derivative comprises a protein shell and lipid and is obtained by a process comprising the steps of:

a. connecting a patient to a device for withdrawing blood;

b. withdrawing blood containing blood cells from the patient;

c. separating the blood cells from the blood to yield a blood fraction containing high density lipoprotein and low density lipoprotein;

d. separating the low density lipoprotein from the blood fraction;

e. mixing the blood fraction with a solvent which removes lipid associated with the high density lipoprotein to yield a mixture of lipid, the solvent, and the particle derivative; and

,

f. separating the particle derivative from the lipid and the solvent, wherein the particle derivative comprises apolipoprotein A1 and phospholipid, and wherein the particle derivative has a reduced lipid content as compared to the high density lipoprotein particle that does not have the solvent treatment.

2. The method of claim 1, wherein steps c through f occur remote from the patient.

3. The method of claim 1, wherein the separation of the low density lipoprotein from the blood fraction is performed using an apheresis device.

4. The method of claim 1, wherein the solvent is at least one of an ether, di-isopropyl ether, sevoflurane, a combination of an alcohol and an ether, or a combination of a sevoflurane and an alcohol.

5. The method of claim 4, wherein the solvent is a mixture of sevoflurane and n-butanol.

6. The method of claim 5, wherein the mixture comprises 95 parts sevoflurane and 5 parts n-butanol.

7. The method of claim 1, wherein the step of separating the particle derivative from the lipid and the solvent is achieved by at least one of an absorbent, separator, centrifuge, or charcoal column.

8. The method of claim 7, wherein the at least one of an absorbent, separator, centrifuge, or charcoal column does not modify the protein shell of the particle derivative.

9. The method of claim 1, further comprising recombining the particle derivative with the blood cells.

10. The method of claim 1, wherein the step of mixing is performed using at least one of a static mixer, vortexer or centrifuge.

11. The method of claim 1, wherein the composition further comprises an acceptable vehicle.