Oxidation-resistant indicator macromolecule

• US 20070014726A1
• Filed: 07/17/2006
• Published: 01/18/2007
• Est. Priority Date: 07/18/2005
• Status: Abandoned Application

• Current Assignee: Sensors For Medicine and Science Incorporated
• Original Assignee: Sensors For Medicine and Science Incorporated
• Inventors: Colvin, Arthur, Merical, Kandace, Mortellaro, Mark
• Application Number:
  US11/487,435
• Publication Number:
  US 20070014726A1
• Time in Patent Office: Days
• US Class Current: 424/9.100
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/0073 semi-solid, gel, hydrogel, ointment
• CPC Class Codes: C09B 57/10 Metal complexes of organic compounds not being dyes in uncomplexed form
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/7783 Transmission, loss
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 21/78 producing a change of colour

Abstract

In one aspect, the present invention relates to an implantable device for detecting the presence or concentration of an analyte in an aqueous environment in vivo. The device includes a macromolecule that comprises a copolymer of: a) one or more indicator component monomers which individually are not sufficiently water soluble to permit their use in an aqueous environment for detecting the presence or concentration of said analyte; b) one or more hydrophilic monomers; and c) one or more catalytic antioxidant monomers; such that the macromolecule is capable of detecting the presence or concentration of the analyte in an aqueous environment. The presence of the catalytic antioxidant reduces or prevents oxidative damage to the macromolecule.

Claims

1. An implantable device for detecting the presence or concentration of an analyte in an aqueous environment in vivo, said device including a macromolecule that comprises a copolymer of:

a) one or more indicator component monomers which individually are not sufficiently water soluble to permit their use in an aqueous environment for detecting the presence or concentration of said analyte;

b) one or more hydrophilic monomers; and

c) one or more catalytic antioxidant monomers;

such that the macromolecule is capable of detecting the presence or concentration of said analyte in an aqueous environment.

2. The implantable device of claim 1, wherein the macromolecule is capable of detection by an optical change.

3. The implantable device of claim 1, wherein the indicator component monomer comprises an N-(o-boronobenzyl)aminomethylanthracene derivative.

4. The implantable device of claim 3, wherein the indicator component monomer is selected from the group consisting of

9-[[N-methacryloylaminopropyl-N-(o-boronobenzyl)amino]-methyl]anthracene;

9-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]anthracene;

9,10-bis[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]anthracene;

9-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]-10-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)-ethylamino]methyl]-10-[N-[2-boronobenzyl)]-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;

9-[N-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N—

[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[2-(carboxyethyl)amino]methyl]anthracene;

and salts or derivatives thereof.

5. The implantable device of claim 3, wherein the hydrophilic monomer comprises [3-(methacryloylamino)-propyl]trimethylammonium chloride.

6. The implantable device of claim 1, wherein the indicator component monomer is selected from the group consisting of a lanthanide chelate and a polyaromatic hydrocarbon.

7. The implantable device of claim 1, wherein the molar ratio of hydrophilic monomer:

indicator component momomer is from about 2;

1 to about 1000;

1.

8. The implantable device of claim 7, wherein the ratio of hydrophilic monomer:

indicator component momomer is from about 5;

1 to about 50;

1.

9. The implantable device of claim 8, wherein the ratio of hydrophilic monomer:

indicator component momomer is about 5;

1.

10. The implantable device of claim 1, wherein the analyte detected is selected from the group consisting of a vicinal diol;

an α

-hydroxy acid, a β

-keto acid oxygen;

carbon dioxide;

zinc, potassium, hydrogen, or carbonate ions;

a toxin;

a mineral; and

a hormone.

11. The implantable device of claim 10, wherein the analyte detected is a vicinal diol which comprises a saccharide.

12. The implantable device of claim 11, wherein the saccharide is glucose.

13. The implantable device of claim 1, wherein

i) the molar ratio of hydrophilic monomer:

indicator component momomer is from about 2;

1 to about 15;

1,

ii) the indicator component monomer comprises an N-(o-boronobenzyl)amino]methyl]anthracene derivative,

iii) the hydrophilic monomer comprises [3-(methacryloylamino)propyl]trimethylammonium chloride, and

iv) the macromolecule exhibits an excimer effect.

14. The implantable device of claim 1, wherein the hydrophilicity of the hydrophilic monomer is increased by the addition of a functional constituent.

15. The implantable device of claim 14, wherein the functional constituent is selected from the group consisting of an ion, a polar moiety, a halogen, and combinations thereof.

16. The implantable device of claim 15, wherein the ion is selected from the group consisting of sulfonate, quartenary amine, carboxyl, and combinations thereof.

17. The implantable device of claim 15, wherein the polar moiety is selected from the group consisting of hydroxyl, sulfhydryl, an amine, carbonyl, an amide, and combinations thereof.

18. The implantable device of claim 1, wherein the catalytic antioxidant monomer comprises a superoxide dismutase mimic monomer which is selected from the group consisting of derivatives of:

CAS RN 218791-21-0;

CAS RN 218791-27-6;

CAS RN 218791-28-7;

CAS RN 301664-32-4;

CAS RN 301664-47-1;

CAS RN 311767-56-3;

CAS RN 311767-57-4;

CAS RN 311767-59-6;

CAS RN 330626-36-3;

CAS RN 330626-39-6;

CAS RN 330626-40-9;

CAS RN 330626-41-0;

CAS RN 330626-42-1;

CAS RN 330626-43-2;

CAS RN 330626-45-4;

CAS RN 330626-47-6;

CAS RN 330626-49-8;

CAS RN 330626-51-2;

CAS RN 330626-52-3;

CAS RN 330626-53-4;

CAS RN 330626-54-5;

CAS RN 330626-55-6;

CAS RN 330626-56-7;

CAS RN 330626-57-8;

CAS RN 330626-58-9;

CAS RN 330626-59-0;

CAS RN 330626-60-3;

CAS RN 330626-61-4;

CAS RN 330626-62-5;

CAS RN 330626-63-6;

CAS RN 330626-64-7;

CAS RN 330626-65-8;

CAS RN 330626-66-9;

CAS RN 330626-67-0;

CAS RN 330626-68-1;

CAS RN 330626-69-2;

CAS RN 330626-70-5;

CAS RN 330626-71-6;

CAS RN 330626-72-7;

CAS RN 330626-73-8;

CAS RN 330626-74-9;

CAS RN 330626-75-0;

CAS RN 330626-76-1;

CAS RN 331718-71-9; and

CAS RN 331718-72-0.

59. The implantable device of claim 1, wherein the indicator component monomer is selected from the group consisting of:

N-[3-(methacrylamido)propyl]-3,4-dihydroxy-9,10-dioxo-2-anthracenesulfonamide;

α

,α

′

-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]-1,4-xylene;

and salts or derivatives thereof.

19. A method for detecting the presence or concentration of an analyte in a sample having an aqueous environment in vivo, said method comprising:

a) exposing the sample to an implantable device that includes an indicator macromolecule, said macromolecule comprising a copolymer of;

i) one or more indicator component monomers which individually are not sufficiently water soluble to permit their use in an aqueous environment for detecting the presence or concentration of said analyte;

ii) one or more hydrophilic monomers; and

iii) one or more catalytic antioxidant monomers;

such that the resulting macromolecule is capable of detecting the presence or concentration of said analyte in an aqueous environment, and wherein the indicator macromolecule has a detectable quality that changes in a concentration-dependent manner when said macromolecule is exposed to said analyte; and

b) measuring any change in said detectable quality to thereby determine the presence or concentration of said analyte in said sample.

20. The method of claim 19, wherein the change in said detectable quality is an optical change.

21. The method of claim 19, wherein the indicator component monomer comprises an N-(o-boronobenzyl)aminomethylanthracene derivative.

22. The method of claim 21, wherein the indicator component monomer is selected from the group consisting of

9-[[N-methacryloylaminopropyl-N-(o-boronobenzyl)amino]-methyl]anthracene;

9-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]anthracene;

9,10-bis[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methylanthracene;

9-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]-10-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)-ethylamino]methyl]-10-[N-[2-boronobenzyl)]-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;

9-[N-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N—

[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[2-(carboxyethyl)amino]methyl]anthracene;

and salts or derivatives thereof.

23. The method of claim 19, wherein the hydrophilic monomer comprises [3-(methacryloylamino)-propyl]trimethylammonium chloride.

24. The method of claim 19, wherein the indicator component monomer is selected from the group consisting of a lanthanide chelate and a polyaromatic hydrocarbon.

25. The method of claim 19, wherein the molar ratio of hydrophilic monomer:

indicator component momomer is from about 2;

1 to about 1000;

1.

26. The method of claim 25, wherein the ratio of hydrophilic monomer:

indicator component momomer is from about 5;

1 to about 50;

1.

27. The method of claim 26, wherein the ratio of hydrophilic monomer:

indicator component momomer is about 5;

1.

28. The method of claim 19, wherein the analyte detected is selected from the group consisting of a vicinal diol;

an α

-hydroxy acid;

a β

-keto acid;

oxygen;

carbon dioxide;

zinc, potassium, hydrogen, or carbonate ions;

a toxin;

a mineral; and

a hormone.

29. The method of claim 28, wherein the analyte detected is a vicinal diol which comprises a saccharide.

30. The method of claim 29, wherein the saccharide is glucose.

31. The method of claim 19, wherein

i) the molar ratio of hydrophilic monomer:

indicator component momomer is from about 2;

1 to about 15;

1,

ii) the indicator component monomer comprises an N-(o-boronobenzyl)aminomethylanthracene derivative,

iii) the hydrophilic monomer comprises [3-(methacryloylamino)propyl]trimethylammonium chloride, and

iv) the macromolecule exhibits an excimer effect.

32. The method of claim 31, wherein said macromolecule serves as both an indicator and a reference.

33. The method of claim 19, wherein the hydrophilicity of the hydrophilic monomer is increased by the addition of a functional constituent.

34. The method of claim 33, wherein the functional constituent is selected from the group consisting of an ion, a polar moiety, a halogen, and combinations thereof.

35. The method of claim 34, wherein the ion is selected from the group consisting of sulfonate, quartenary amine, carboxyl, and combinations thereof.

36. The method of claim 34, wherein the polar moiety is selected from the group consisting of hydroxyl, sulfhydryl, an amine, carbonyl, an amide, and combinations thereof.

37. The method of claim 19, wherein the catalytic antioxidant monomer comprises a superoxide dismutase mimic monomer which is selected from the group consisting of derivatives of:

CAS RN 218791-21-0;

CAS RN 218791-27-6;

CAS RN 218791-28-7;

CAS RN 301664-32-4;

CAS RN 301664-47-1;

CAS RN 311767-56-3;

CAS RN 311767-57-4;

CAS RN 311767-59-6;

CAS RN 330626-36-3;

CAS RN 330626-39-6;

CAS RN 330626-40-9;

CAS RN 330626-41-0;

CAS RN 330626-42-1;

CAS RN 330626-43-2;

CAS RN 330626-45-4;

CAS RN 330626-47-6;

CAS RN 330626-49-8;

CAS RN 330626-51-2;

CAS RN 330626-52-3;

CAS RN 330626-53-4;

CAS RN 330626-54-5;

CAS RN 330626-55-6;

CAS RN 330626-56-7;

CAS RN 330626-57-8;

CAS RN 330626-58-9;

CAS RN 330626-59-0;

CAS RN 330626-60-3;

CAS RN 330626-61-4;

CAS RN 330626-62-5;

CAS RN 330626-63-6;

CAS RN 330626-64-7;

CAS RN 330626-65-8;

CAS RN 330626-66-9;

CAS RN 330626-67-0;

CAS RN 330626-68-1;

CAS RN 330626-69-2;

CAS RN 330626-70-5;

CAS RN 330626-71-6;

CAS RN 330626-72-7;

CAS RN 330626-73-8;

CAS RN 330626-74-9;

CAS RN 330626-75-0;

CAS RN 330626-76-1;

CAS RN 331718-71-9; and

CAS RN 331718-72-0.

60. The method of claim 19, wherein the indicator component monomer is selected from the group consisting of:

N-[3-(methacrylamido)propyl]-3,4-dihydroxy-9,10-dioxo-2-anthracenesulfonamide;

α

,α

′

-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]-1,4-xylene;

and salts or derivatives thereof.

38. An implantable device that is capable of exhibiting an excimer effect, said device including a macromolecule which comprises a copolymer of:

a) one or more excimer forming monomers, the molecules of which are capable of exhibiting an excimer effect when suitably oriented with respect to each other; and

b) one or more other monomers comprising a catalytic antioxidant;

such that the resulting macromolecule exhibits said excimer effect.

39. The implantable device of claim 38, wherein the macromolecule is capable of detecting the presence or concentration of an analyte.

40. The implantable device of claim 39, wherein

a) the excimer forming monomer individually is not sufficiently water soluble to permit its use in an aqueous environment for detecting the presence or concentration of said analyte;

and

b) the other monomer is a hydrophilic monomer;

such that the macromolecule is capable of detecting the presence or concentration of said analyte in an aqueous environment.

41. The implantable device of claim 39, wherein the excimer effect does not substantially change in response to changes in the presence or concentration of the analyte.

42. The implantable device of claim 41, wherein

i) the molar ratio of other monomer:

excimer forming momomer is from about 2;

1 to about 15;

1,

ii) the excimer forming monomer comprises an N-(o-boronobenzyl)aminomethylanthracene derivative, and

iii) the other monomer comprises [3-(methacryloylamino)propyl]trimethylammonium chloride.

43. The implantable device of claim 38, wherein the excimer forming monomer is selected from the group consisting of a lanthanide chelate and a polyaromatic hydrocarbon.

44. The implantable device of claim 42, wherein the excimer forming monomer is selected from the group consisting of

9-[[N-methacryloylaminopropyl-N-(o-boronobenzyl)amino]-methyl]anthracene;

9-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]-10-[N-(2-boronbenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]anthracene;

9,10-bis[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methylanthracene;

9-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]-10-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)-ethylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(carboxyetbyl)amino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;

9-[N-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N—

[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[2-(carboxyethyl)amino]methyl]anthracene;

and salts or derivatives thereof.

45. The implantable device of claim 38, wherein the hydrophilicity of the hydrophilic monomer is increased by the addition of a functional constituent.

46. The implantable device of claim 45, wherein the functional constituent is selected from the group consisting of an ion, a polar moiety, a halogen, and combinations thereof.

47. The implantable device of claim 46, wherein the ion is selected from the group consisting of sulfonate, quartenary amine, carboxyl, and combinations thereof.

48. The implantable device of claim 46, wherein the polar moiety is selected from the group consisting of hydroxyl, sulfhydryl, an amine, carbonyl, an amide, and combinations thereof.

49. The implantable device of claim 38, wherein the catalytic antioxidant monomer comprises a superoxide dismutase mimic monomer which is selected from the group consisting of derivatives of:

CAS RN 218791-21-0;

CAS RN 218791-27-6;

CAS RN 218791-28-7;

CAS RN 301664-32-4;

CAS RN 301664-47-1;

CAS RN 311767-56-3;

CAS RN 311767-57-4;

CAS RN 311767-59-6;

CAS RN 330626-36-3;

CAS RN 330626-39-6;

CAS RN 330626-40-9;

CAS RN 330626-41-0;

CAS RN 330626-42-1;

CAS RN 330626-43-2;

CAS RN 330626-45-4;

CAS RN 330626-47-6;

CAS RN 330626-49-8;

CAS RN 330626-51-2;

CAS RN 330626-52-3;

CAS RN 330626-53-4;

CAS RN 330626-54-5;

CAS RN 330626-55-6;

CAS RN 330626-56-7;

CAS RN 330626-57-8;

CAS RN 330626-58-9;

CAS RN 330626-59-0;

CAS RN 330626-60-3;

CAS RN 330626-61-4;

CAS RN 330626-62-5;

CAS RN 330626-63-6;

CAS RN 330626-64-7;

CAS RN 330626-65-8;

CAS RN 330626-66-9;

CAS RN 330626-67-0;

CAS RN 330626-68-1;

CAS RN 330626-69-2;

CAS RN 330626-70-5;

CAS RN 330626-71-6;

CAS RN 330626-72-7;

CAS RN 330626-73-8;

CAS RN 330626-74-9;

CAS RN 330626-75-0;

CAS RN 330626-76-1;

CAS RN 331718-71-9; and

CAS RN 331718-72-0.

61. The implantable device of claim 38, wherein the excimer forming monomer is selected from the group consisting of:

N-[3-(methacrylamido)propyl]-3,4-dihydroxy-9,10-dioxo-2-anthracenesulfonamide;

α

,α

′

-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]-1,4-xylene;

and salts or derivatives thereof.

50. A method for detecting the presence or concentration of an analyte in a sample in vivo, said method comprising:

a) exposing the sample to an an implantable device that includes an indicator macromolecule, said macromolecule comprising a copolymer of;

i) one or more indicator component monomers, the molecules of which are capable of exhibiting an excimer effect when suitably oriented with respect to each other, and which are also capable of detecting the presence or concentration of an analyte; and

ii) one or more other monomers, comprising a catalytic antioxidant;

such that the resulting macromolecule exhibits said excimer effect, and wherein the indicator macromolecule has a detectable quality that changes in a concentration-dependent manner when said macromolecule is exposed to said analyte; and

b) measuring any change in said detectable quality to thereby determine the presence or concentration of said analyte in said sample.

51. The method of claim 50, wherein the excimer effect does not substantially change in response to changes in the presence or concentration of the analyte.

52. The method of claim 51, wherein

i) the molar ratio of other monomer:

indicator component momomer is from about 2;

1 to about 15;

1,

ii) the indicator component monomer comprises an N-(o-boronobenzyl)amino]methyl]anthracene derivative, and

iii) the other monomer comprises [3-(methacryloylamino)propyl]trimethylammonium chloride.

53. The method of claim 50, wherein the indicator component monomer is selected from the group consisting of a lanthanide chelate and a polyaromatic hydrocarbon.

54. The method of claim 51, wherein the indicator component monomer is selected from the group consisting of

9-[[N-methacryloylaminopropyl-N-(o-boronobenzyl)amino]-methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)-ethylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]-anthracene; and

9,10-bis[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;

9-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]anthracene;

9,10-bis[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]anthracene;

9-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]-10-[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;

N-[3-(methacrylamido)propyl]-3,4-dihydroxy-9,10-dioxo-2-anthracenesulfonamide;

α

,α

′

-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]-1,4-xylene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]methyl]anthracene;

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;

9-[N-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N—

[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[2-(carboxyethyl)amino]methyl]anthracene;

and salts or derivatives thereof.

55. The method of claim 50, wherein the hydrophilicity of the hydrophilic monomer is increased by the addition of a functional constituent.

56. The method of claim 55, wherein the functional constituent is selected from the group consisting of an ion, a polar moiety, a halogen, and combinations thereof.

57. The method of claim 56, wherein the ion is selected from the group consisting of sulfonate, quartenary amine, carboxyl, and combinations thereof.

58. The method of claim 56, wherein the polar moiety is selected from the group consisting of hydroxyl, sulfhydryl, an amine, carbonyl, an amide, and combinations thereof.

62. The method of claim 50, wherein the indicator component monomer is selected from the group consisting of:

N-[3-(methacrylamido)propyl]-3,4-dihydroxy-9,10-dioxo-2-anthracenesulfonamide;

α

,α

′

-bis[N-[2-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]-1,4-xylene;

and salts or derivatives thereof.

63. An implantable device for detecting the presence or concentration of an analyte in an aqueous environment in vivo, said device including a macromolecule that comprises a copolymer of:

a) one or more indicator component monomers which individually are not sufficiently water soluble to permit their use in an aqueous environment for detecting the presence or concentration of said analyte; and

b) one or more hydrophilic monomers;

such that the macromolecule is capable of detecting the presence or concentration of said analyte in an aqueous environment, and wherein at least one catalytic antioxidant is attached to said macromolecule.

64. The implantable device of claim 63, wherein the catalytic antioxidant is covalently attached to the macromolecule.

65. The implantable device of claim 63, wherein the catalytic antioxidant comprises a superoxide dismutase mimic.

66. The implantable device of claim 65, wherein the superoxide dismutase mimic is selected from the group consisting of derivatives of:

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