Hydrophilic light absorbing compositions for determination of physiological function in critically ill patients

• US 20040223913A1
• Filed: 12/23/2003
• Published: 11/11/2004
• Est. Priority Date: 10/16/2000
• Status: Active Grant

• Current Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Original Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Inventors: Rajagopalan, Raghavan, Dorshow, Richard B., Achilefu, Samuel, Bugaj, Joseph E., Periasamy, Muthunadar P.
• Granted Patent: US 7,297,325 B2
• Time in Patent Office: Days
• US Class Current: 424/9.6
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0032 Methine dyes, e.g. cyanine dyes
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/12 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 209/58 [b]- or [c]-condensed
• CPC Class Codes: C07D 209/60 Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles

Abstract

Highly hydrophilic indole and benzoindole derivatives that absorb and fluoresce in the visible region of light are disclosed. These compounds are useful for physiological and organ function monitoring. Particularly, the molecules of the invention are useful for optical diagnosis of renal and cardiac diseases and for estimation of blood volume in vivo.

Claims

1. A pharmaceutical composition comprising an effective amount of a compound of Formula 2

5. The composition as in claims 1, 2, 3 or 4 further comprising a contrast agent.

6. The composition as in claims 1, 2, 3 or 4 wherein the compound comprises a radioactive halogen.

7. The composition as in claims 1, 2, 3 or 4 wherein at least one R group of the compound is replaced by a polyamino carboxylic acid or its derivative.

8. The composition as in claim 7 further comprising a radioactive metal ion or a paramagnetic metalion.

9. The composition as in claims 1, 2, 3, 4, 6, or 7 formulated as at least one of a liposome, a micelle, a microcapsule, or a microparticle.

10. The composition as in claims 1, 2, 3, 4, 6, or 7 formulated as at least one of ultra small iron oxide particles, silver particles, or gold particles.

29. A method of imaging a patient comprising administering a non-optical contrast agent composition further comprising the compound of any of claims 1, 2, 3, 4, 7, or 8 and performing at least one of an optical imaging procedure or a non-optical imaging procedure.

30. The method of claim 29 wherein the non-optical contrast agent composition is chosen from a magnetic resonance composition, a computed tomography composition, an x-ray composition, a nuclear imaging composition, a positron emission tomography composition, a single photon emission computed tomography composition, an optoacoustic composition, and an ultrasound composition.

31. The method of claim 29 wherein the compound stabilizes or buffers the non-optical contrast agent.

2. A pharmaceutical composition comprising an effective amount of a compound of Formula 2

3. A pharmaceutical composition comprising an effective amount of a compound of Formula 2

4. A pharmaceutical composition comprising an effective amount of a compound of Formula 2

11. A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of a compound of formula 2

15. The method as in claims 11, 12, 13, or 14 wherein said procedure utilizes light of wavelength in the region of 350-1300 nm.

16. The method of claim 15 wherein said procedure comprises monitoring a blood clearance profile by fluorescence using light of wavelength in the region of 350 nm to 1300 nm.

17. The method as in claims 11, 12, 13, or 14 wherein said procedure comprises monitoring a blood clearance profile by absorption using light of wavelength in the region of 350 nm to 1300 nm.

18. The method as in claims 11, 12, 13, or 14 wherein the compound contains a radioactive halogen and imaging the mammal by at least one of optical imaging and nuclear imaging.

19. The method as in claims 11, 12, 13, or 14 where the compound administered has at least one R group replaced by a polyamino carboxylic acid or its derivative.

20. The method of claim 19 wherein the compound administered further comprises a radioactive metal ion or a paramagnetic metalion.

21. The method as in claims 11, 12, 13, 14, 19, or 20 further comprising imaging by at least one of optical imaging, nuclear imaging, or magnetic resonance imaging.

22. The method as in claims 11, 12, 13, 14, 18, or 19 wherein the compound is administered in a formulation selected from at least one of liposome, micelles, microcapsules, or microparticles.

23. The method as in claims 11, 12, 13, 14, 18, 19, or 20 wherein the compound is administered in a formulation selected from at least one of ultra small iron oxide particles, silver particles, or gold particles.

24. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 further comprising administering a non-optical contrast agent and imaging by at least one of magnetic resonance, ultrasound, x-ray, positron emission tomography, computed tomography, optoacoustic imaging, and single photon emission computed tomography.

25. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 wherein said procedure is for physiological function monitoring.

26. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 wherein said procedure is for at least one of renal function monitoring, cardiac function monitoring, and kidney function monitoring.

27. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22, or 23 wherein said procedure is for determining organ perfusion in vivo.

28. The method as in claims 11, 12, 13, 14, 18, 19, 20, 21, 22 or 23 further comprising optically imaging the mammal.

12. A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of a compound of formula 2

13. A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of a compound of formula 2

14. A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of a compound of formula 2