SMMR (small molecule metabolite reporters) for use as in vivo glucose biosensors

• US 8,466,286 B2
• Filed: 08/22/2011
• Issued: 06/18/2013
• Est. Priority Date: 12/24/2003
• Status: Active Grant

• Current Assignee: Cercacor Laboratories
• Original Assignee: Cercacor Laboratories
• Inventors: Bellott, Emile M., Bu, Dongsheng, Childs, James J., Lambert, Christopher, Nienaber, Hubert A., Shi, Shirley J., Wang, Zhaolin, Workman, Jerome J., Zelenchuk, Alex R.
• Primary Examiner(s): Desai, Rita
• Assistant Examiner(s): Michelson, Ben S
• Application Number:
  US13/215,061
• Publication Number:
  US 20120052018A1
• Time in Patent Office: 666 Days
• Field of Search: None
• US Class Current: 546/13
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0041 Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal in vivo G01N
• CPC Class Codes: A61K 49/0052 Small organic molecules oligomers, polymers, dendrimers A61K49/0054
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

Small Molecule Metabolite Reporters (SMMRs) for use as in vivo glucose biosensors, sensor compositions, and methods of use, are described. The SMMRs include boronic acid-containing xanthene, coumarin, carbostyril and phenalene-based small molecules which are used for monitoring glucose in vivo, advantageously on the skin.

Claims

1. A small molecule metabolite reporter compound having a structure represented by the following formula:

2. The compound of claim 1, wherein D is O.

3. The compound of claim 1, wherein D is N.

4. The compound of claim 1, wherein at least one of R₉ and R₁₀, is M, and wherein M has a structure represented by Formula (A):

5. The compound of claim 4, wherein R₁₀ is M, and wherein M has a structure represented by Formula (A).

6. The compound of claim 1, wherein at least one of R₉ and R₁₀, is M, and wherein M has a structure represented by Formula (B):

7. The compound of claim 6, wherein R₉ is M, and wherein M has a structure represented by Formula (B).

8. The compound of claim 1, wherein at least one of R₉ and R₁₀, is M, and wherein M has a structure represented by Formula (C):

9. A method of measuring a compound or metabolite thereof, comprising:

containing the compound of claim 1 with an area of a mammalian body where the compound or metabolite may be found; and

detecting a photometric change in the compound, wherein the change is indicative of a property of the compound or metabolite thereof.

10. The method of claim 9, wherein the compound is glucose.

11. The method of claim 9, wherein the area of the body is skin.

12. The method of claim 9, wherein the area of the body is the stratum corneum.

13. The method of claim 9, wherein the area of the body is the epidermis.