Indocyanine compound, synthesis method and purification method thereof, diagnostic composition using the indocyanine compound, and device for measuring biokinetics and device for visualizing circulation using the diagnostic composition

Patent metadata

Field	Value
Publication number	US-10086090-B2
Application number	US-201715438047-A
Country	US
Kind code	B2
Filing date	Feb 21, 2017
Priority date	Jan 28, 2010
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

Abstract

The present invention aims at providing a novel indocyanine compound solving problems of conventionally used indocyanine green, such as solubility in water or physiological saline, a synthesis method and a purification method thereof, and a diagnostic composition including the novel indocyanine compound. Further, provided are a method for evaluating biokinetics of the novel indocyanine compound and a device for measuring biokinetics, and a method and a device for visualizing circulation of fluid such as blood in a living body, which utilize the diagnostic composition. Also, found are a novel indocyanine compound in which a hydrophobic moiety in a near-infrared fluorescent indocyanine molecule is included in a cavity of a cyclic sugar chain cyclodextrin to cover the hydrophobic moiety in the indocyanine molecule with the glucose, and a synthesis method and a purification method thereof. Furthermore, found are a method for fluorescence-imaging an organ other than liver by intravenous administration, a method for evaluating biokinetics of the novel indocyanine compound, a device for measuring biokinetics, and a method and a device for visualizing circulation of fluid such as blood in a living body, utilizing the diagnostic composition including the novel indocyanine compound.

First claim

The invention claimed is:

1. A cyclodextrin-bonded indocyanine cation of formula (15), (16), (19) or (20):

wherein in the formulas (16) and (20), the indocyanine structure has at least a portion of a naphthyl group included in a cavity of a cyclodextrin.

2. The cyclodextrin-bonded indocyanine cation of claim 1 , which has the formula (15) or (16).

3. The cyclodextrin-bonded indocyanine cation of claim 1 , which has the formula (19) or (20).

4. A composition, comprising:
the cyclodextrin-bonded indocyanine cation of claim 1 .

5. The composition of claim 4 , further comprising:
water.

6. The composition of claim 5 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

7. The composition of claim 5 , wherein the cyclodextrin-bonded indocyanine cation has the formula (19) or (20).

8. The composition of claim 4 , which is in a form capable of being dissolved in water to provide an aqueous solution.

9. The composition of claim 8 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

10. The composition of claim 8 , wherein the cyclodextrin-bonded indocyanine cation has the formula (19) or (20).

11. A solid cyclodextrin-bonded indocyanine of formula (16) or (20):

wherein in the formulas (16) and (20), the indocyanine structure has at least a portion of a naphthyl group included in a cavity of a cyclodextrin.

12. The solid cyclodextrin-bonded indocyanine of claim 11 , which has the formula (20).

13. The solid cyclodextrin-bonded indocyanine of claim 12 , which has an ESI-MS m/z [M] value corresponding to a molecular formula C 135 H 197 N 4 O 73 .

14. The solid cyclodextrin-bonded indocyanine of claim 12 , which is produced by a method including
mixing a compound of formula (18) with a compound of formula (14) in a medium to obtain a mixture:

mixing a dehydration-condensing agent with the mixture to perform a dehydration-condensation reaction of the mixture, and
optionally performing an inclusion reaction in water.

15. The solid cyclodextrin-bonded indocyanine of claim 12 , which is produced by purification through column chromatography and elution with a medium including an acid selected from the group consisting of hydrochloric acid, trifluoroacetic acid, acetic acid, sulfuric acid, nitric acid and formic acid.

16. The solid cyclodextrin-bonded indocyanine of claim 12 , which is produced by purification through column chromatography and elution with a medium including hydrochloric acid.

17. The solid cyclodextrin-bonded indocyanine of claim 11 , which has the formula (16).

18. The solid cyclodextrin-bonded indocyanine of claim 17 , which has a ESI-MS m/z [M] + value corresponding to a molecular formula C 131 H 191 N 4 O 72 .

19. The solid cyclodextrin-bonded indocyanine of claim 17 , which is produced by a method including
mixing a compound of formula (13) with a compound of formula (14) in a medium to obtain a mixture:

mixing a dehydration-condensing agent with the mixture to perform a dehydration-condensation reaction of the mixture, and
optionally performing an inclusion reaction in water.

20. The solid cyclodextrin-bonded indocyanine of claim 17 , which is produced by purification through column chromatography and elution with a medium including an acid selected from the group consisting of hydrochloric acid, trifluoroacetic acid, acetic acid, sulfuric acid, nitric acid and formic acid.

21. The solid cyclodextrin-bonded indocyanine of claim 17 , which is produced by purification through column chromatography and elution with a medium including hydrochloric acid.

22. A composition, comprising:
the solid cyclodextrin-bonded indocyanine of claim 11 .

23. The composition of claim 22 , wherein the solid cyclodextrin-bonded indocyanine has the formula (20).

24. The composition of claim 22 , wherein the solid cyclodextrin-bonded indocyanine has the formula (16).

Assignees

• National Univ Corporation Mie Univ
• Univ Nagoya Nat Univ Corp
• National Univ Corporaton Nagoya Univ

Inventors

• Teranishi Katsunori
• Hirata Hitoshi
• Arai Tetsuya

Classifications

• A61K49/0017

  Fluorescence in vivo · CPC title

• A61B5/418

  lymph vessels, ducts or nodes · CPC title

• C09B23/086

  more than five >CH- groups · CPC title

• A61B5/0071

  by measuring fluorescence emission · CPC title

• C09B68/485

  Substituted non-aromatic cyclic groups · CPC title