Antiproliferative compositions comprising curcumin analogs and methods of producing and using same

Patent metadata

Field	Value
Publication number	US-9359196-B2
Application number	US-201113279766-A
Country	US
Kind code	B2
Filing date	Oct 24, 2011
Priority date	Sep 10, 2009
Publication date	Jun 7, 2016
Grant date	Jun 7, 2016

Abstract

Antiproliferative compositions that include CLEFMA, as well as liposomal compositions containing said antiproliferative compositions, are disclosed. Also disclosed are methods of making and using the antiproliferative compositions and liposomal compositions.

First claim

What is claimed is:

1. A curcumin analog composition, comprising 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (CLEFMA).

2. The curcumin analog composition of claim 1 , further comprising 2-hydroxypropyl-beta-cyclodextrin (HPβCD).

3. The curcumin analog composition of claim 1 , further comprising glutathione.

4. The curcumin analog composition of claim 1 , further comprising at least one additional molecule/agent selected from the group consisting of a Cox-2 inhibitor, an anti-cancer agent, an anti-inflammatory agent, an anti-oxidant, a targeting moiety, a polyethylene glycol molecule, a labeling moiety, and combinations thereof.

5. A liposomal composition comprising:
a lipid composition; and
a curcumin analog composition comprising 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (CLEFMA) encapsulated within a liposomal structure formed by the lipid composition.

6. The liposomal composition of claim 5 , wherein the lipid composition is further defined as an anionic non-phospholipid having the structure represented by the following general formula [1]:

wherein R is NH or O; R′ is at least one of a hydrogen (H), an alkyl group (such as but not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, hexadecyl), Na, Li, K, a metal, or a halogen; R″ is at least one of a —CH 2 — group and a —CH 2 CH 2 — group; and n and x are each an 8-16 carbon chain.

7. The liposomal composition of claim 6 , wherein the lipid composition is selected from the group consisting of 2-carboxyheptadecanoyl heptadecylamide (CHHDA); 1,4-dipalmitoyl-tartarate-2,3-disuccinic acid (DPTSA); 1,4-dipalmitoyl-tartarate-2,3-diglutaric acid (DPTGA); 1,4-disteroyl-tartarate-2,3-disuccinic acid (DSTSA); and cholesteryl hemisuccinate (CHEMS).

8. The liposomal composition of claim 6 , further comprising at least one additional lipid composition is selected from the group consisting of phosphatidylcholine, phosphoethanolamine, phosphatidylglycerol, and a sterol lipid.

9. The liposomal composition of claim 6 , wherein the anionic non-phospholipid is present in a range of from about 1% to about 30% of the total lipid present in the liposomal structure, and wherein the liposomal structure comprises a particle size in a range of from about 50 nm to about 500 nm, and a volume average particle size in a range of from about 10 nm to about 5,000 nm.

10. The liposomal composition of claim 5 , further comprising at least one molecule/agent selected from the group consisting of 2-hydroxypropyl-beta-cyclodextrin (HPβCD), glutathione, a Cox-2 inhibitor, an anti-cancer agent, an anti-inflammatory agent, an anti-oxidant, a targeting moiety, a polyethylene glycol molecule, a labeling moiety, and combinations thereof.

11. A method of forming a liposomal composition, comprising the steps of:
disposing an anionic non-phospholipid composition and a curcumin analog composition in an aqueous solution, wherein the curcumin analog composition comprises 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (CLEFMA), and wherein the anionic non-phospholipid composition has the structure represented by the following general formula [1]:

wherein R is NH or O; R′ is at least one of a hydrogen (H), an alkyl group (such as but not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, hexadecyl), Na, Li, K, a metal, or a halogen; R″ is at least one of a —CH 2 — group and a —CH 2 CH 2 — group; and n and x are each an 8-16 carbon chain; and

dispersing same to form the liposomal structure having the curcumin analog composition encapsulated therein.

Assignees

• Awasthi Vibhudutta
• Lagisetty Pallavi
• Agashe Hrushikesh
• Univ Oklahoma

Inventors

• Awasthi Vibhudutta
• Lagisetty Pallavi
• Agashe Hrushikesh

Classifications

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/724

  Cyclodextrins · CPC title

• A61K31/45

  having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide · CPC title

• C08L5/16

  Cyclodextrin; Derivatives thereof · CPC title