Quaternary nitrogen heterocyclic compounds for detecting aqueous monosaccharides in physiological fluids

• US 8,569,502 B2
• Filed: 12/24/2012
• Issued: 10/29/2013
• Est. Priority Date: 06/27/2003
• Status: Active Grant

• Current Assignee: Chris Geddes
• Original Assignee: Chris Geddes
• Inventors: Geddes, Chris D., Badugu, Ramachandram, Lakowicz, Joseph R.
• Primary Examiner(s): Seaman, D M
• Application Number:
  US13/726,445
• Publication Number:
  US 20130210158A1
• Time in Patent Office: 309 Days
• Field of Search: 546/102, 546/104
• US Class Current: 546/102
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/193333 In aqueous solution

Abstract

Quaternary nitrogen heterocyclic boronic acid-containing compounds are described, which are sensitive to glucose and fructose, as well as a variety of other physiologically important analytes, such as aqueous chloride and iodide, and a method of using the compounds. Also disclosed is a contact lens doped with the quaternary nitrogen heterocyclic boronic acid-containing compound, and a method of using the doped contact lens to measure the concentration of analyte in tears under physiological conditions.

Claims

1. A fluorescence compound selected from the group consisting of:

2. The compound of claim 1, wherein the fluorescence intensity of the compound changes in the presence of analytes.

3. The compound of claim 2, wherein the analyte comprise a species selected from the group consisting of glucose, fructose, chloride and iodide.

4. The compound of claim 1, wherein the fluorescence intensity of the compound decreases in the presence of glucose.

5. A method of measuring the concentration of an analyte in a physiological fluid, said method comprising:

(a) contacting a fluorescence compound selected from the group consisting of;

6. The method of claim 5, wherein the physiological fluid is blood, tears, interstitial fluid or aqueous humor.

7. An assay kit for measuring the concentration of an analyte in a physiological fluid comprising a container containing a fluorescence compound selected from the group consisting of:

8. The kit of claim 7, wherein the physiological fluid is blood.

9. An ophthalmic sensor comprising:

a polymer matrix comprising a fluorescence compound contracting at least the outer surface of the polymer matrix, wherein the fluorescence compound interacts or reacts with an analyte to provide an optical signal which is indicative of the analyte concentration in an ocular fluid and wherein the fluorescence compound is at least one member selected from the group consisting of;

10. The ophthalmic sensor of claim 9, wherein the ophthalmic device is a contact lens and the fluorescence compound is coated on the surface of the contact lens of impregnated into the polymeric matrix.

11. The ophthalmic sensor of claim 9, wherein the analyte comprises a species selected from the group consisting of glucose, fructose, chloride, and iodide.

12. The ophthalmic sensor of claim 9, wherein the substrate is implantable.

13. The ophtahlmic sensor of claim 9, wherein the optical signal is fluorescence and is measured based on the intensity, lifetime, anisotropy or ratiometric fluorescence platforms.