Polymerized micelles for diagnosis

Patent metadata

Field	Value
Publication number	US-9839700-B2
Application number	US-201113816414-A
Country	US
Kind code	B2
Filing date	Jul 7, 2011
Priority date	Aug 9, 2010
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

The invention relates to polymerized micelles of size inferior to 100 nm for in vivo diagnosis, in particular of cancer. The polymerized micelles of the invention comprise a diagnostic agent and an amphiphilic polymer obtainable by the polymerization of an amphiphilic monomer, said monomer comprising: a lipophilic chain comprising a polymerizable vinylic or diacetylenic group, and a hydrophilic head comprising a polyoxyethylene or polyoxypropylene chain. The invention finds application in the pharmaceutical field, in particular.

First claim

The invention claimed is:

1. A method of in vivo diagnosis comprising: administering an effective amount of a polymerized micelle comprising:
a diagnostic agent; and
an amphiphilic polymer obtainable by the polymerization of an amphiphilic monomer, the monomer comprising a hydrophilic head comprising a polyoxyethylene chain;
wherein:
the polymerized micelle has a hydrodynamic diameter of less than 30 nm; and
the amphiphilic monomer is of formula (I):
X-L 0 -[L 1 -Y] k -L 2

wherein:
X is —(CH 2 —CH 2 —O) n —Z;
Y is —C≡C—C≡C—;
L 0 is a bond;
L 1 is —(CH 2 ) p —;
L 2 is —(CH 2 ) q —CH 3 ;
Z is H, or —CH 2 —COOH;
n is an integer from 5 to 230;
k is an integer from 1 to 5;
p is at each occurrence an integer from 1 to 24; and
q is an integer from 1 to 24.

2. The method of claim 1 , wherein the diagnostic agent is cancer diagnostic agent.

3. The method of claim 2 , wherein the diagnostic agent is a fluorescent compound.

4. The method of claim 2 , wherein the diagnostic agent is either coupled with a hydrophilic head or loaded in the micelle.

5. The method of claim 1 , wherein n is 8 or 45.

6. The method of claim 1 , wherein the amphiphilic polymer is obtained by the polymerization of a mixture comprising a first amphiphilic monomer wherein Z is H and a second amphiphilic monomer of formula (I) wherein Z is —CH,—COOH.

7. The method of claim 6 , wherein the amphiphilic polymer further comprises a targeting entity.

8. The method of claim 7 , wherein the targeting entity is an aptamer.

9. A polymerized micelle comprising: an amphiphilic polymer obtainable by the polymerization of an amphiphilic monomer of formula (I):
X-L 0 -[L 1 -Y] k -L 2
wherein:
X is —(CH 2 —CH 2 —O) —Z;
Y is —C≡C—C≡C—;
L 0 is a bond;
L 1 is —(CH 2 ) p —;
L 2 is —(CH 2 ) q —CH 3 ;
Z is H or —CH 2 —COOH;
n is an integer from 5 to 230;
k is an integer from 1 to 5;
p is at each occurrence an integer from 1 to 24; and
q is an integer from 1 to 24;

and wherein the polymerized micelle has a hydrodynamic diameter of less than 30 nm.

10. The polymerized micelle of claim 9 , wherein a group Z of the polymerized micelle is coupled to a diagnostic agent.

11. A method of preparing a polymerized micelle of claim 9 , the method comprising:
i) self-assembling the amphiphilic monomer of formula (I) into micelles; and
ii) polymerizing self-assembled micelles obtained in step i).

12. A diagnostic composition comprising a polymerized micelle of claim 9 .

13. The method of claim 11 , further comprising coupling a Z group of the obtained polymerized micelle with a diagnostic agent.

14. The composition of claim 12 , further comprising a pharmaceutically acceptable excipient.

15. The polymerized micelle of claim 10 , wherein the diagnostic agent is a substance emitting electromagnetic rays or a substance detectable by X-ray, ultrasound or nuclear magnetic resonance.

16. The method of claim 1 , wherein L 0 is a bond.

Assignees

• Doris Eric
• Duconge Frédéric
• Gravel Edmond
• Mackiewicz Nicolas
• Tavitian Bertrand
• Commissariat Energie Atomique

Inventors

• Doris Eric
• Duconge Frédéric
• Gravel Edmond
• Mackiewicz Nicolas
• Tavitian Bertrand

Classifications

• A61K49/0082 Primary

  micelle, e.g. phospholipidic micelle and polymeric micelle · CPC title

• A61K9/1075

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

• A61K49/0054

  Macromolecular compounds, i.e. oligomers, polymers, dendrimers · CPC title

• A61K49/0032

  Methine dyes, e.g. cyanine dyes · CPC title