HIGH ENERGY RADIATION INSENSITIVE ANALYTE SENSORS

• US 20130189720A1
• Filed: 03/10/2011
• Published: 07/25/2013
• Est. Priority Date: 03/16/2010
• Status: Active Grant

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Edwards Lifesciences Corporation
• Inventors: Petisce, James R.
• Granted Patent: US 8,895,252 B2
• Time in Patent Office: Days
• US Class Current: 435/25
• CPC Class Codes: A61B 2562/18 Shielding or protection of sensors from environmental influences, e.g. protection from mechanical damage
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: C12Q 1/26 involving oxidoreductase
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements

Abstract

Enzyme based analyte sensors having radiation stabilizing agents are disclosed and described. More particularly, devices comprising a radiation stabilizing agent and methods for stabilizing sensors to high energy radiation sterilization are disclosed and described.

Claims

1. An enzyme-based analyte sensor comprising at least one enzyme and at least one radiation stabilizing agent.

2. The enzyme-based analyte sensor of claim 1, wherein the radiation stabilizing agent comprises at least one of a hindered amine light stabilizer, an antioxidant, or a vitamin in an amount sufficient to stabilize the at least one enzyme to high energy radiation.

3. The enzyme-based analyte sensor of claim 2, wherein the hindered amine light stabilizer comprises one or more of polymethylpropyl 3-oxy-[4(2,2,6,6 tetramethyl) piperidinyl]siloxane (Uvasil 299);

poly[[.beta.-[1,1,3,3-tetramethyl butyl)amino]-s-triazine-2,4-diyl][[2,2,6,6-tetramethyl-4-piperidyl)imino]hexamethylene[(2,2,6,6,-tetramethyl-4-piperidyl)imino]] (Chimassorb

     944);

1,3,5-triazine-2,4,6-triamine, N,N′

″

-[1,2-ethanediylbis[[[4.6-bis[butyl (1,2,2,6,6-pentamethyl-4-piperidinyl)amino]-1,3,5-triazine-2-yl]imino]-3,1 propanedyl]]-bis[N′

,N″

-dibutyl-N′

,N″

-bis(1,2,2,6,6-pentamethyl-4-piperidinyl)- (Chimassorb

     119);

alkyl substituted piperidinyl alkandioic acid esters;

bis(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate;

bis-(1-octyloxy-2,2,6,6,tetramethyl-4-piperidinyl)sebacate (Tinuvin

     123);

bis(1,2,2,6,6-pentamethyl-4-piperidinyl)-[[3,5-bis(1, 1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate (Tinuvin

     144);

1,1′

-(1,2-ethanediyl)bis(3,3,5,5-tetramethylpiperazinone);

dimethyl succinate polymer with 4-hydroxy-2,2,6,6-tetramethyl-1-piperidineethanol (Tinuvin

     622);

poly((6-((1,1.3.3-tetramethylbutyl)amino)-s-triazine-2,4-diyl)(t-(2,2,6,6-tetramethyl-4-piperidyl) iminohexa-methylene((2,2,6,6-tetramethyl-4-piperidyl)imino)) and dimethyl succinate polymer with 4-hydroxy 2,2,6,6-tetramethyl-1-piperidineethanol (Tinuvin

     783);

1,3,5-triazine-2,4,6-triamine, N2,N2′

-1,2-ethanediylbis[N2-[3-[[4,6-bis[butyl(1,2,2,6,6-pentamethyl-4-piperidinyl)amino]-1,3,5-triazin-2-yl]amino]propyl]-N4,N6-dibutyl-N4, N6-bis(1,2,2,6,6-pentamethyl-4-piperidinyl)- (Lowilite

     19);

polymer of dimethyl succinate and 4-hydroxy-2,2,6,6-tetramethyl-1-piperidine ethanol (Lowilite

     62);

Bis(2,2,6,6-tetramethyl-4-piperidyl)sebacate (Lowilite

     77);

mixture of bis(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate and methyl(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate (Lowilite

     92);

or poly [[6-[1,1,3,3-tetramethylbutyl)amino]-1,3,5-triazine-2,4-diyl][2,2,6,6tetramethyl-4-piperidyl)imino]hexamethylene[(2,2,6,6-tetramethyl-4-piperidyl]iminol]] (Lowilite

     94).

4. The enzyme-based analyte sensor of claim 2, wherein the radiation stabilizer comprises at least one of a polymeric hindered phenol, a polymeric aromatic amine, a polymer with thioester or phosphorous containing apendages, a polymeric hydroxyl amine, a polymeric benzofuranone derivative, and polymeric acrylated bis-phenol.

5. The enzyme-based analyte sensor of any one of the previous claims, further comprising an interference layer.

6. The enzyme-based analyte sensor of claim 5, wherein the interference layer comprises the radiation stabilizing agent.

7. The enzyme-based analyte sensor of any one of claims 1-5, further comprising a flux limiting membrane.

8. The enzyme-based analyte sensor of claim 7, wherein the flux limiting membrane comprises the radiation stabilizing agent.

9. The enzyme-based analyte sensor of claim 1, wherein the enzyme based analyte sensor is configured for a catheter.

10. The enzyme-based analyte sensor of claim 1, wherein the enzyme is presented in an enzyme layer, the enzyme layer comprising a hydrophilic polymer.

11. The enzyme-based analyte sensor of claim 10, wherein the hydrophilic polymer of the comprises at least one of a poly-N-vinylpyrrolidone, a poly-N-vinyl-3-ethyl-2-pyrrolidone, a poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, a polyvinylimidazole, a poly-N—

N-dimethylacrylamide, a polyacrylamide, and copolymers thereof.

12. The enzyme-based analyte sensor of claim 10, wherein the hydrophilic polymer is poly-N-vinylpyrrolidone.

13. The enzyme-based analyte sensor of claim 10, wherein the enzyme layer comprises poly-N-vinylpyrrolidone, glucose oxidase and at least one radiation stabilizing agent.

14. An electrochemical enzyme-based analyte sensor comprising:

at least one electrode having an electroactive surface;

an enzyme layer comprising at least one enzyme;

at least one radiation stabilizer;

at least one membrane layer, the membrane covering at least a portion of the electroactive surface.

15. The enzyme-based analyte sensor of claim 14, wherein the radiation stabilizing agent comprises at least one hindered amine light stabilizers, antioxidants, vitamins, and polymeric versions thereof.

16. The enzyme-based analyte sensor of claim 15, wherein the hindered amine light stabilizers comprises one or more of polymethylpropyl 3-oxy-[4(2,2,6,6 tetramethyl) piperidinyl]siloxane (Uvasil 299);

poly[[.beta.-[1,1,3,3-tetramethyl butyl)amino]-s-triazine-2,4-diyl][[2,2,6,6-tetramethyl-4-piperidyl]imino]hexamethylene[(2,2,6,6,-tetramethyl-4-piperidyl)imino]] (Chimassorb

     944);

1,3,5-triazine-2,4,6-triamine, N,N′

″

-[1,2-ethanediylbis[[[4.6-bis[butyl (1,2,2,6,6-pentamethyl-4-piperidinyl)amino]-1,3,5-triazine-2-yl]imino]-3,1 propanedyl]]-bis[N′

,N″

-dibutyl-N′

,N″

-bis(1,2,2,6,6-pentamethyl-4-piperidinyl)- (Chimassorb

     119);

alkyl substituted piperidinyl alkandioic acid esters;

bis(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate;

bis-(1-octyloxy-2,2,6,6,tetramethyl-4-piperidinyl)sebacate (Tinuvin

     123);

bis(1,2,2,6,6-pentamethyl-4-piperidinyl)-[[3,5-bis(1, 1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate (Tinuvin

     144);

1,1′

-(1,2-ethanediyl)bis(3,3,5,5-tetramethylpiperazinone);

dimethyl succinate polymer with 4-hydroxy-2,2,6,6-tetramethyl-1-piperidineethanol (Tinuvin

     622);

poly((6-((1,1.3.3-tetramethylbutyl)amino)-s-triazine-2,4-diyl)(t-(2,2,6,6-tetramethyl-4-piperidyl) iminohexa-methylene((2,2,6,6-tetramethyl-4-piperidyl)imino)) and dimethyl succinate polymer with 4-hydroxy 2,2,6,6-tetramethyl-1-piperidineethanol (Tinuvin

     783);

1,3,5-triazine-2,4,6-triamine, N2,N2′

-1,2-ethanediylbis[N2-[3-[[4,6-bis[butyl(1,2,2,6,6-pentamethyl-4-piperidinyl)amino]-1,3,5-triazin-2-yl]amino]propyl]-N4,N6-dibutyl-N4, N6-bis(1,2,2,6,6-pentamethyl-4-piperidinyl)- (Lowilite

     19);

polymer of dimethyl succinate and 4-hydroxy-2,2,6,6-tetramethyl-1-piperidine ethanol (Lowilite

     62);

Bis(2,2,6,6-tetramethyl-4-piperidyl)sebacate (Lowilite

     77);

mixture of bis(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate and methyl(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate (Lowilite

     92);

or poly[[6-[(1,1,3,3-tetramethylbutyl)amino]-1,3,5-triazine-2,4-diyl][(2,2,6,6 tetramethyl-4-piperidyl)imino]hexamethylene[(2,2,6,6-tetramethyl-4-piperidyl]iminol]] (Lowilite

     94).

17. The enzyme-based analyte sensor of claim 15, wherein the radiation stabilizer comprises at least one of a polymeric hindered phenol, a polymeric aromatic amine, a polymer with thioester or phosphorous containing appendages, a polymeric hydroxyl amine, a polymeric benzofuranone derivative, and polymeric acrylated bis-phenol.

18. The enzyme-based analyte sensor of claim 14, wherein the at least one membrane layer is an interference layer.

19. The enzyme-based analyte sensor of claim 14, wherein the interference layer comprises the radiation stabilizer.

20. The enzyme-based analyte sensor of claim 14, wherein the enzyme layer comprises a hydrophilic polymer and the radiation stabilizer.

21. The enzyme-based analyte sensor of claim 20, wherein the hydrophilic polymer of the enzyme layer comprises a material selected from the group consisting of poly-N-vinylpyrrolidone, poly-N-vinyl-3-ethyl-2-pyrrolidone, poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole, poly-N—

N-dimethylacrylamide, polyacrylamide, and copolymers thereof.

22. The enzyme-based analyte sensor of claim 20, wherein the hydrophilic polymer of the enzyme layer is poly-N-vinylpyrrolidone.

23. The enzyme-based analyte sensor of claim 14, wherein the at least one membrane layer comprises vinyl ester monomeric units.

24. A method of stabilizing an enzyme-based sensor subjected to sterilizing radiation, the method comprising:

providing an enzyme-based analyte sensor, the sensor comprising;

at least one enzyme; and

at least one radiation stabilizing agent in an amount sufficient to stabilize the enzyme to an amount of high energy radiation sufficient to sterilize the enzyme-based analyte sensor.

25. The method of claim 24, wherein the enzyme-based sensor is an intravenous blood glucose sensor (IVBG).

26. The method of any one of claims 24-25, wherein the radiation stabilizing agent comprises a at least one of hindered amine light stabilizers, antioxidants, vitamins, and combinations thereof.

27. The method of claim 26, wherein the hindered amine light stabilizers comprise wherein the hindered amine light stabilizers comprises one or more of polymethylpropyl 3-oxy-[4(2,2,6,6 tetramethyl) piperidinyl]siloxane (Uvasil 299);

poly[[.beta.-[1,1,3,3-tetramethyl butyl)amino]-s-triazine-2,4-diyl][[2,2,6,6-tetramethyl-4-piperidyl]imino]hexamethylene[(2,2,6,6,-tetramethyl-4-piperidyl)imino]] (Chimassorb

     944);

1,3,5-triazine-2,4,6-triamine, N,N′

″

-[1,2-ethanediylbis[[[4.6-bis[butyl (1,2,2,6,6-pentamethyl-4-piperidinyl)amino]-1,3,5-triazine-2-yl]imino]-3,1 propanedyl]]-[-bis[N′

,N″

-dibutyl-N′

,N″

-bis(1,2,2,6,6-pentamethyl-4-piperidinyl)- (Chimassorb

     119);

alkyl substituted piperidinyl alkandioic acid esters;

bis(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate;

bis-(1-octyloxy-2,2,6,6,tetramethyl-4-piperidinyl)sebacate (Tinuvin

     123);

bis(1,2,2,6,6-pentamethyl-4-piperidinyl)-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate (Tinuvin

     144);

1,1′

-(1,2-ethanediyl)bis(3,3,5,5-tetramethylpiperazinone);

dimethyl succinate polymer with 4-hydroxy-2,2,6,6-tetramethyl-1-piperidineethanol (Tinuvin

     622);

poly((6-((1,1.3.3-tetramethylbutyl)amino)-s-triazine-2,4-diyl)(t-(2,2,6,6-tetramethyl-4-piperidyl) iminohexa-methylene((2,2,6,6-tetramethyl-4-piperidyl)imino)) and dimethyl succinate polymer with 4-hydroxy 2,2,6,6-tetramethyl-1-piperidineethanol (Tinuvin

     783);

1,3,5-triazine-2,4,6-triamine, N2,N2′

-1,2-ethanediylbis[N2-[3-[[4,6-bis[butyl(1,2,2,6,6-pentamethyl-4-piperidinyl)amino]-1,3,5-triazin-2-yl]amino]propyl]-N4,N6-dibutyl-N4, N6-bis(1,2,2,6,6-pentamethyl-4-piperidinyl)- (Lowilite

     19);

polymer of dimethyl succinate and 4-hydroxy-2,2,6,6-tetramethyl-1-piperidine ethanol (Lowilite

     62);

Bis(2,2,6,6-tetramethyl-4-piperidyl)sebacate (Lowilite

     77);

mixture of bis(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate and methyl(1,2,2,6,6-pentamethyl-4-piperidinyl)sebacate (Lowilite

     92);

or poly[[6-[(1,1,3,3-tetramethylbutyl)amino]-1,3,5-triazine-2,4-diyl][(2,2,6,6 tetramethyl-4-piperidyl)imino]hexamethylene[(2,2,6,6-tetramethyl-4-piperidyl]imino]] (Lowilite

     94).

28. The method of any one of claims 24-25, wherein the radiation stabilizer comprises at least one of a polymeric hindered phenol, a polymeric aromatic amine, a polymer with thioester or phosphorous containing apendages, a polymeric hydroxylamine, a polymeric benzofuranone derivative, and polymeric acrylated bis-phenol.

29. The method of any one of claim 24-25 or 27, further comprising subjecting the enzyme-based sensor to a calibration source prior to exposing the enzyme-based sensor to high energy radiation.

30. The method of any one of claim 24 or 29, further comprising preventing removal of the radiation stabilizing agent from contact with a solution prior to sterilization.

31. The method of claim 30, wherein the radiation stabilizing agent is non-fugitive, wherein the molecular weight of the radiation stabilizing agent is greater than about 1000 Daltons, or the radiation stabilizing agent is essentially insoluble in the solution.