Fluorescent probe for imaging lymph nodes

Patent metadata

Field	Value
Publication number	US-9302018-B2
Application number	US-201113700780-A
Country	US
Kind code	B2
Filing date	May 31, 2011
Priority date	May 31, 2010
Publication date	Apr 5, 2016
Grant date	Apr 5, 2016

Abstract

Disclosed is a near-infrared fluorescent imaging agent comprising an indocyanine-based fluorescent dye and a liposome. The near-infrared fluorescent imaging agent of the present invention demonstrates high fluorescence intensity and a long anchoring time in sentinel lymph nodes, thereby making it useful for detecting sentinel lymph nodes in sentinel lymph node navigation surgery. Also disclosed is an indocyanine green derivative that is particularly suitable for use in the near-infrared fluorescent imaging agent of the present invention.

First claim

The invention claimed is:

1. A compound represented by chemical formula (I):

wherein, Y represents —C(CH 3 ) 2 —, Z1 and Z2 together form a benzene ring fused with the ring to which they are bound, Z3 and Z4 together form a benzene ring fused with the ring to which they are bound, R 1 represents —(CH 2 ) n —SO 3 , n (with respect to R 1 ) is 4, R 2 is

wherein X 1 represents —CONH— and X 2 represents —OCO—, B represents a monovalent cation which is a hydrogen ion, lithium ion, sodium ion or potassium ion, R 3 represents an alkane group, alkene group or alkyne group having 1 to 18 carbon atoms, n (with respect to R 2 ) is 2, and p is 2.

2. A compound represented by chemical formula (VII):

wherein, R 1 and R 2 represent a hexanoyl group, octanoyl group, decanoyl group, dodecanoyl group, tetradecanoyl group, hexadecanoyl group, octadecanoyl group, or oleoyl group.

3. A liposome comprising the compound according to claim 1 .

4. A compound according to claim 1 , which is represented by the formula:

5. A liposome comprising the compound according to claim 2 .

6. A liposome comprising the compound according to claim 4 .

7. A fluorescent probe for near-infrared fluorescent imaging in sentinel lymphadenography comprising a liposome according to claim 3 .

8. A fluorescent probe for near-infrared fluorescent imaging in sentinel lymphadenography comprising a liposome according to claim 5 .

9. A fluorescent probe for near-infrared fluorescent imaging in sentinel lymphadenography comprising a liposome according to claim 6 .

10. A near-infrared fluorescent imaging agent, comprising a compound according to claim 1 .

11. A near-infrared fluorescent imaging agent, comprising a compound according to claim 2 .

12. A near-infrared fluorescent imaging agent, comprising a compound according to claim 4 .

13. A compound represented by the formula:

14. A near-infrared fluorescent imaging agent, comprising a compound according to claim 13 .

15. A liposome comprising the compound according to claim 13 .

16. A fluorescent probe for near-infrared fluorescent imaging in sentinel lymphadenography comprising a liposome according to claim 15 .

Assignees

• Hayashi Hideki
• Fujinami Masanori
• Toyota Taro
• Tamura Yutaka
• Aoki Akira
• Muraki Yutaka
• Onoue Kazuki
• Eisai R&D Man Co Ltd

Inventors

• Hayashi Hideki
• Fujinami Masanori
• Toyota Taro
• Tamura Yutaka
• Aoki Akira
• Muraki Yutaka
• Onoue Kazuki

Classifications

• A61K49/0032

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

• C09B23/086

  more than five >CH- groups · CPC title

• A61K49/0084 Primary

  liposome, i.e. bilayered vesicular structure · CPC title

• C07D209/60

  Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title