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

• US 8,048,015 B2
• Filed: 03/24/2008
• Issued: 11/01/2011
• Est. Priority Date: 07/03/2003
• Status: Active Grant

• Current Assignee: HDL Therapeutics, LLC
• Original Assignee: HDL Therapeutics, LLC
• Inventors: Perlman, Timothy Jon, Brewer, H. Bryan Jr., Conner, Adam Paul, Bellotti, Marc, Akeefe, Hassibullah
• Primary Examiner(s): KAM, CHIH MIN
• Application Number:
  US12/054,162
• Publication Number:
  US 20080234621A1
• Time in Patent Office: 1,317 Days
• Field of Search: 604/5.03, 514/2, 514/12, 530/359, 424/491, 210/749
• US Class Current: 604/5.03
• 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 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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: A61P 9/12 Antihypertensives
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• 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 of modifying a protein distribution in a fluid, wherein the protein distribution has a first state, the first state having alpha high density lipoproteins and pre-beta high density lipoproteins, comprising the steps of:

exposing the fluid to a lipid removing agent wherein the exposure modifies the protein distribution from the first state into a second state, the second state having an increased concentration of pre-beta high density lipoproteins relative to the first state; and

,

removing the lipid removing agent from the fluid,

wherein the lipid removing agent comprises sevoflurane.

2. The method of claim 1, wherein the fluid is plasma.

3. The method of claim 1, wherein the lipid removing agent comprises at least one of an ether, di-isopropyl ether, alcohol, or n-butanol.

4. The method of claim 1, wherein the lipid removing agent is a mixture of sevoflurane and n-butanol.

5. The method of claim 1, wherein the fluid comprises low density lipoproteins prior to exposing the fluid to the lipid removing agent.

6. The method of claim 5, wherein the low density lipoproteins are not removed from the fluid prior to exposing the fluid to the lipid removing agent.

7. The method of claim 6, wherein the fluid is exposed to the lipid removing agent using an extracorporeal process, wherein the fluid exposure leaves low density lipoproteins substantially unmodified as compared to the low density lipoproteins in the fluid prior to exposure of the fluid to the lipid removing agent.

8. The method of claim 7, wherein the extracorporeal process transforms at least some of the alpha high density lipoproteins into pre-beta high density lipoproteins.

9. The method of claim 8, wherein the pre-beta high density lipoproteins transformed from the alpha high density lipoproteins have a lower cholesterol content than the alpha high density lipoproteins.

10. The method of claim 1, wherein the low density lipoproteins are not in the fluid when the fluid is exposed to the lipid removing agent.

11. The method of claim 10, wherein the exposure of the fluid to the lipid removing agent transforms at least some of the alpha high density lipoproteins into pre-beta high density lipoproteins.

12. The method of claim 11, wherein the pre-beta high density lipoproteins transformed from the alpha high density lipoproteins have a lower cholesterol content than the alpha high density lipoproteins.

13. The method of claim 10, wherein the low density lipoproteins are removed from the fluid prior to exposing the fluid to the lipid removing agent using an extracorporeal process.

14. The method of claim 1, wherein the first state has more alpha high density lipoproteins than pre-beta high density lipoproteins.

15. The method of claim 14, wherein the second state has more pre-beta high density lipoproteins than alpha high density lipoproteins.

16. The method of claim 1, wherein the fluid with the modified protein distribution is administered to a patient.

17. The method of claim 16, wherein the fluid with the modified protein distribution is autologous to the patient.

18. The method of claim 16, wherein the fluid with the modified protein distribution is not autologous to the patient.

19. The method of claim 1, wherein the fluid is a biological fluid.

20. A method of modifying a protein distribution in a fluid, wherein the protein distribution has a first state, the first state having more alpha high density lipoproteins than pre-beta high density lipoproteins, comprising the steps of:

exposing the fluid to a lipid removing agent wherein the exposure modifies the protein distribution from the first state into a second state, the second state having more pre-beta high density lipoproteins than alpha high density lipoproteins; and

,

removing the lipid removing agent from the fluid,

wherein the lipid removing agent comprises sevoflurane.

21. The method of claim 20, wherein Apolipoprotein B (ApoB) proteins associated with low density lipoproteins are in the fluid.

22. The method of claim 21, wherein the ApoB proteins are substantially unaffected by the lipid removing agent.

23. The method of claim 20, wherein the fluid is plasma.

24. The method of claim 20, wherein the fluid is a biological fluid.