Tempamine compositions and methods of use

• US 20040219201A1
• Filed: 12/05/2002
• Published: 11/04/2004
• Est. Priority Date: 12/06/2001
• Status: Abandoned Application

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Wasserman, Veronica, Barenholz, Yechezkel
• Application Number:
  US10/314,487
• Publication Number:
  US 20040219201A1
• Time in Patent Office: Days
• US Class Current: 424/450
• 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 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• 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 33/06 Antimalarials
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A therapeutic composition comprised of tempamine for treatment of conditions caused by oxidative stress or cellular oxidative damage is described. In one embodiment, the tempamine is administered in a vehicle suitable to extend its blood circulation lifetime. For example, tempamine is loaded into the liposomes that provide an extended blood circulation lifetime for effective therapy against inflammation or cell proliferation.

Claims

1. A composition for treatment of a condition resulting from cellular oxidative damage, comprising

liposomes comprised of a vesicle-forming lipid and between about 1-20 mole percent of a lipid derivatized with a hydrophilic polymer and tempamine entrapped in said liposomes.

4. The composition of claim 1, wherein said tempamine is entrapped in the liposome at a concentration sufficient to achieve precipitation in the presence of a co-entrapped counter-ion.

5. The composition of claim 1, wherein the liposome further comprises cholesterol.

6. The composition of claim 1, wherein said vesicle-forming lipid is hydrogenated phosphatidylcholine.

7. The composition of claim 1, wherein said hydrophilic polymer is polyethylene glycol.

8. The composition of claim 4, wherein said counterion is sulfate.

2. (Cancelled)

3. (Cancelled)

9. A method for treating a condition caused by oxidative damage to a cell, comprising

administering to the cell liposomes comprised of a vesicle-forming lipid and between about 1-20 mole percent of a lipid derivatized with a hydrophilic polymer and tempamine entrapped in said liposomes.

12. The method of claim 9, wherein said preparing includes entrapping said tempamine in said liposomes at a concentration sufficient to achieve precipitation in the presence of a co-entrapped counterion.

13. The method of claim 9, wherein said preparing further comprises preparing liposomes comprised of the vesicle-forming lipid hydrogenated phosphatidyl choline.

14. The method of claim 9, wherein said preparing further comprises preparing liposomes that comprise cholesterol.

15. The method of claim 9, wherein said preparing further comprises preparing liposomes where said hydrophilic polymer is polyethylene glycol.

16. The method of claim 9 further comprising the step of co-administering a chemotherapeutic agent.

17. The method of claim 16, wherein said co-administering includes co-administering said second agent entrapped in liposomes comprised of a vesicle-forming lipid derivatized with a hydrophilic polymer.

18. The method of claim 16, wherein said second agent is selected from the group consisting of doxorubicin, daunorubicin, cisplatin, taxol, and camptothecin analogues.

10. (Cancelled)

11. (Cancelled)

19. A method for enhancing the chemotherapeutic activity of a chemotherapeutic agent, comprising,

administering tempamine to a subject being treated with a chemotherapeutic agent.

20. The method of claim 19, wherein said administering includes administering tempamine entrapped in liposomes.

21. The method of claim 19, wherein said chemotherapeutic agent is administered in liposome-entrapped form.

22. The method of claim 20, wherein said liposomes are comprised of (i) vesicle-forming lipids, (ii) between about 1-20 mole percent of a lipid derivatized with a hydrophilic polymer.

23. The method of claim 20, wherein said tempamine is entrapped in the liposomes at a concentration sufficient to achieve precipitation in the presence of a co-entrapped counterion.

24. The method of claim 19, whereby said administering provides an increase in the number of apoptotic cell deaths.