Method of delivering an anti-cancer agent to a cell

Patent metadata

Field	Value
Publication number	US-9248200-B2
Application number	US-73966808-A
Country	US
Kind code	B2
Filing date	Oct 23, 2008
Priority date	Oct 23, 2007
Publication date	Feb 2, 2016
Grant date	Feb 2, 2016

Abstract

There is provided a delivery vehicle comprising an anti-cancer agent together with a conjugate of a delivery agent containing a free aldehyde and a flavonoid, having the delivery agent conjugated at the C6 and/or the C8 position of the A ring of the flavonoid. The resulting delivery vehicles may be used to deliver an anti-cancer agent to a cell.

First claim

What is claimed is:

1. A micellar nanocomplex comprising:
trastuzumab; and
a conjugate of:
(i) aldehyde-terminated polyethylene glycol; and
(ii) a flavonoid that is either monomeric (−)-epigallocatechin gallate or oligomeric (−)-epigallocatechin gallate,

the micellar nanocomplex having the polethylene glycol conjugated at the C6 and/or the C8 position of the A ring of the flavonoid by attachment of the polyethylene glycol via reaction of the free aldehyde group with the C6 and/or C8 position of the A ring of the flavonoid, and exhibiting an anti-cancer effect on a cell as a result of a synergistic effect between the anti-cancer effect of the trastuzumab and the anti-cancer effect of the flavonoid,
wherein when the flavonoid is monomeric (−)-epigallocatechin gallate, the micellar nanocomplex further comprises non-conjugated oligomeric (−)-epigallocatechin gallate in an inner core of the micellar nanocomplex,
wherein the trastuzumab is complexed with either the conjugated or non-conjugated oligomeric (−)-epigallocatechin gallate, whichever is present.

2. The micellar nanocomplex of claim 1 wherein the aldehyde-terminated polyethylene glycol is conjugated to oligomeric (−)-epigallocatechin gallate.

3. The micellar nanocomplex of claim 2 , wherein the oligomeric (−)-epigallocatechin gallate is formed from (−)-epigallocatechin gallate monomers that have been oligomerized through enzyme-catalyzed oxidative coupling.

4. The micellar nanocomplex of claim 2 , wherein the oligomeric (−)-epigallocatechin gallate is formed from (−)-epigallocatechin gallate monomers that have been oligomerized through aldehyde-mediated oligomerization.

5. The micellar nanocomplex of claim 2 , wherein the oligomeric (−)-epigallocatechin gallate is formed from (−)-epigallocatechin gallate monomers that have been oligomerized through a carbon-carbon linkage between the C6 or C8 position on the A ring of a first monomeric unit to the C6 or C8 position on the A ring of a second monomeric unit.

6. The micellar nanocomplex of claim 1 wherein the aldehyde-terminated polyethylene glycol is conjugated to monomeric (−)-epigallocatechin gallate and the micellar nanocomplex comprises an inner core containing non-conjugated oligomeric (−)-epigallocatechin gallate.

7. The micellar nanocomplex of claim 6 , wherein the oligomeric (−)-epigallocatechin gallate is formed from (−)-epigallocatechin gallate monomers that have been oligomerized through enzyme-catalyzed oxidative coupling.

8. The micellar nanocomplex of claim 6 , wherein the oligomeric (−)-epigallocatechin gallate is formed from (−)-epigallocatechin gallate monomers that have been oligomerized through aldehyde-mediated oligomerization.

9. The micellar nanocomplex of claim 6 , wherein the oligomeric (−)-epigallocatechin gallate is formed from (−)-epigallocatechin gallate monomers that have been oligomerized through a carbon-carbon linkage between the C6 or C8 position on the A ring of a first monomeric unit to the C6 or C8 position on the A ring of a second monomeric unit.

10. A pharmaceutical composition comprising the micellar nanocomplex according to claim 1 .

11. A pharmaceutical composition comprising the micellar nanocomplex according to claim 2 .

12. A pharmaceutical composition comprising the micellar nanocomplex according to claim 6 .

13. A method of delivering trastuzumab to a cell comprising contacting the micellar nanocomplex of claim 1 with the cell.

14. The method according to claim 13 , wherein the cell is in vitro.

15. The method according to claim 13 , wherein the cell is in vivo and the method comprises administering the micellar nanocomplex to a subject in need of anti-cancer treatment.

Assignees

• Ying Jackie Y
• Chung Joo Eun
• Kurisawa Motoichi
• Agency Science Tech & Res

Inventors

• Ying Jackie Y
• Chung Joo Eun
• Kurisawa Motoichi

Classifications

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61K47/50 Primary

  the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates · CPC title

• A61K47/6919

  the form being a ribbon or a tubule cochleate · CPC title

• A61K9/1075 Primary

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• C08G65/3326

  aromatic · CPC title