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

• US 7,608,244 B2
• Filed: 07/16/2007
• Issued: 10/27/2009
• Est. Priority Date: 10/16/2000
• Status: Expired due to Fees

• 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.
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US11/778,447
• Publication Number:
  US 20070269368A1
• Time in Patent Office: 834 Days
• Field of Search: 424/1.11, 424/1.37, 424/1.49, 424/1.65, 424/1.69, 424/1.73, 424/1.81, 424/1.85, 424/1.89, 424/9.1, 424/9.2, 424/9.3, 424/9.4, 424/9.5, 424/9.6, 424/9.7, 424/9.8, 548/100, 548/146, 548/215, 514/2, 514/5, 514/6, 514/156, 514/183, 514/359, 514/430, 514/449, 514/471
• US Class Current: 424/9.1
• 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 compound of Formula 2

2. The compound of claim 1 wherein R₈ is C1 alkyl.

3. The compound of claim 1 wherein R₉ to R₁₄ is —

H or —

SO₃T.

4. The compound of claim 1 wherein Y₂ is selected from the group consisting of —

(CH₂)_d—

CO₂T, —

(CH₂)_aNHSO₃T, —

CH₂—

(CH₂—

O—

CH₂)_g—

CH₂—

NH₂, and —

(CH₂)_h—

N(R_a)—

(CH₂)_i—

CO₂T.

5. The compound of claim 1 wherein W₂ is S;

and Y₂ is selected from the group consisting of —

(CH₂)_aNHSO₃T, —

CH₂—

(CH₂—

O—

CH₂)_g—

CH₂—

NH₂, and —

(CH₂)_h—

N(R_a)—

(CH₂)_i—

CO₂T.

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

7. The composition of claim 6 further comprising a contrast agent.

8. The composition of claim 6 wherein the compound comprises a radioactive halogen.

9. The composition of claim 6 wherein at least one R group of the compound is replaced by a polyamino carboxylic acid.

10. The composition of claim 6 further comprising a radioactive metal ion or a paramagnetic ion.

11. The composition of claim 6 formulated as at least one of a liposome, a micelle, a microcapsule, or a microparticle.

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. The method of claim 12 further comprising imaging by at least one of optical imaging, nuclear imaging, or magnetic resonance imaging.

14. The method of claim 12 wherein the compound is administered in a formulation selected from at least one of liposome, micelles, microcapsules, or microparticles.

15. The method of claim 12 wherein the compound is administered in a formulation selected from at least one of ultra small iron oxide particles, silver particles, or gold particles.

16. The method of claim 12 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.

17. The method of claim 12 wherein said procedure is for physiological function monitoring selected from least one of renal function monitoring, cardiac function monitoring, or kidney function monitoring determining organ perfusion in vivo.

18. The method of claim 12 further comprising optically imaging the mammal.

19. The method of claim 16 wherein the non-optical contrast agent composition is selected from the group consisting of 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.

20. The method of claim 16 wherein the compound stabilizes or buffers the non-optical contrast agent.