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-9844606-B2
Application number	US-201514616117-A
Country	US
Kind code	B2
Filing date	Feb 6, 2015
Priority date	Jan 28, 2010
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

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 method of diagnosing at least one of an organ, a body fluid, and a vessel in a living body by near-infrared fluorescence, comprising:
administering to the living body a composition comprising water and at least one of cyclodextrin-bonded indocyanine cations of formulas (15), (16), (19), (20), (21), (23), (24) and (25):

applying excitation light to the at least one of cyclodextrin-bonded indocyanine cations in the living body; and
diagnosing the at least one of the organ, the body fluid, and the vessel based on distribution data of the at least one of cyclodextrin-bonded indocyanine cations in the living body.

2. The method of claim 1 , wherein at least one of a blood vessel, lymph vessel, brain, eye, stomach, breast, esophagus, skin, kidney, ureter, bladder, urethra, lung, and heart is diagnosed.

3. The method of claim 2 , wherein blood circulation is visualized in a blood vessel.

4. The method of claim 3 , wherein necrosis is diagnosed.

5. The method of claim 3 , wherein the blood vessel is a coronary artery.

6. The method of claim 3 , wherein the blood vessel is an abdominal blood vessel.

7. The method of claim 3 , wherein blood circulation failure is diagnosed.

8. The method of claim 2 , wherein tissue engagement after revascularization or transplant operation is diagnosed.

9. The method of claim 2 , wherein the method provides at least one of eyeground imaging, evaluation of a cerebral circulation, imaging during brain surgery, identification of a sentinel lymph node, evaluation of lymphedema, intraoperative cholangiography, marking of tumor, coronary artery imaging, and an abdominal blood vessel imaging.

10. The method of claim 1 , wherein the body fluid visualized is at least one of blood, lymph fluid, interstitial fluid and urine.

11. The method of claim 10 , wherein the body fluid visualized is blood.

12. The method of claim 10 , wherein the body fluid visualized is lymph fluid.

13. The method of claim 10 , wherein the body fluid visualized is interstitial fluid.

14. The method of claim 10 , wherein the body fluid visualized is urine.

15. A method of visualizing at least one of kidney, ureter, bladder, and urethra, comprising:
intravenously administering to a living body a composition comprising water and at least one of cyclodextrin-bonded indocyanine cations of formulas (15), (16), (19), (20), (21), (23), (24) and (25):

applying excitation light to the at least one of cyclodextrin-bonded indocyanine cations in the living body; and
visualizing the at least one of kidney, ureter, bladder and urethra based on distribution data of the at least one of cyclodextrin-bonded indocyanine cations in the living body.

16. The method of claim 15 , wherein the kidney is visualized.

17. The method of claim 15 , wherein the ureter is visualized.

18. The method of claim 15 , wherein the bladder is visualized.

19. The method of claim 15 , wherein the urethra is visualized.

20. A method of visualizing at least one of blood vessel, lymph vessel, brain, eye, stomach, breast, esophagus, skin, kidney, ureter, bladder, urethra, lung and heart, comprising:
administering to a living body a solution comprising water and at least one of cyclodextrin-bonded indocyanine cations of formulas (15), (16), (19), (20), (21), (23), (24) and (25):

applying excitation light to the at least one of cyclodextrin-bonded indocyanine cations in the living body;
obtaining distribution state data of the at least one of cyclodextrin-bonded indocyanine cations in the living body by two-dimensionally acquiring intensity of a fluorescence emitted by the cyclodextrin-bonded indocyanine cation in the living body and two-dimensionally acquiring an intensity of light other than the fluorescence emitted by the cyclodextrin-bonded indocyanine cation excited by the excitation light;
obtaining morphological data of a visualized part of the living body by two-dimensionally acquiring an intensity of light different from the fluorescence emitted by the cyclodextrin-bonded indocyanine cation, and
displaying a distribution state of the cyclodextrin-bonded indocyanine cation in the part of the living body by overlapping the morphological data obtained by the morphological with the distribution state data obtained by the fluorescence imager.

21. The method of claim 20 , wherein the blood vessel is visualized.

22. The method of claim 20 , wherein the lymph vessel is visualized.

23. The method of claim 20 , wherein the kidney is visualized.

24. The method of claim 20 , wherein the ureter is visualized.

25. The method of claim 20 , wherein the bladder is visualized.

26. The method of claim 1 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

27. The method of claim 2 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

28. The method of claim 3 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

29. The method of claim 4 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

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

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

32. The method of claim 7 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

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

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

35. The method of claim 10 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

36. The method of claim 11 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

37. The method of claim 12 , wherein the cyclodextrin-bonded indocyanine cation has the formula (15) or (16).

38. The method of claim 13 , wherein the cyclodextrin-bonded indocyanine cation has

Assignees

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

Inventors

• Teranishi Katsunori
• Hirata Hitoshi
• Arai Tetsuya

Classifications

• A61B5/418

  lymph vessels, ducts or nodes · CPC title

• C08B37/0015

  Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes · CPC title

• A61K49/0093

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title

• C09B68/485

  Substituted non-aromatic cyclic groups · CPC title

• A61B5/026

  Measuring blood flow {(A61B3/1233, A61B3/1241 take precedence)} · CPC title