METHOD AND DEVICE FOR DETECTION OF BIOAVAILABLE DRUG CONCENTRATION IN A FLUID SAMPLE

• US 20120116195A1
• Filed: 10/15/2009
• Published: 05/10/2012
• Est. Priority Date: 10/15/2008
• Status: Active Grant

• Current Assignee: US Department of The Army (Government of the United States of America), University of Memphis Research Foundation
• Original Assignee: United States Of America As Represented By The Secretary Of The Army (Government of the United States of America), University of Memphis Research Foundation, University of Tennessee Research Foundation (University of Tennessee)
• Inventors: Chaum, Edward, Lindner, Erno, Curley, Kenneth C., Guo, Jidong
• Granted Patent: US 9,700,246 B2
• Time in Patent Office: Days
• US Class Current: 600/345
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2205/3303 Using a biosensor
• CPC Class Codes: A61M 25/0017 specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections
• CPC Class Codes: A61M 31/00 Devices for introducing or retaining media, e.g. remedies, in cavities of the body A61M25/00 takes precedence ; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008

Abstract

The invention relates to a method for the controlled delivery of a drug as a function of bioavailable drug concentration, a sensor device for detecting bioavailable drug concentration, and a delivery device that controls delivery of the drug based on the real-time detection of bioavailable drug concentration.

Claims

1-14. -14. (canceled)

15. An electrochemical sensor device comprising two or more electrodes, and a coating that surrounds the two or more electrodes, wherein the coating comprises a structural component, a water immiscible organic solvent, and a charge transfer component, and wherein the coating selectively partitions an electrochemically active drug from a fluid sample whereby an oxidation/reduction current within the coating can be measured using the two or more electrodes.

16. The electrochemical sensor device according to claim 15, wherein the coating further comprises a membrane resistance controlling component selected from the group consisting of lipophilic electrolytes, tetradodecyl ammonium-tetrakis(4-chlorophenyl) borate (ETH500), and bis(triphenylphoranylidene) ammonium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BTPPATFPB);

a biocompatibility enhancing component selected from the group consisting of nitric-oxide releasing sol-gel materials, N-(6-aminohexyl)aminopropyltrimethoxysilane, and balanced isobutyltrimethoxysilane diazeniumdiolate;

or both.

17. The electrochemical sensor device according to claim 15, wherein the electrochemical sensor device is a voltammetric sensor device, a potentiometric sensor device, a conductometric sensor device, or a coulometric sensor device.

18. The electrochemical sensor device according to claim 15, wherein the structural component comprises a polymer selected from the group consisting of polyvinylchloride (PVC), silicone rubber, polyurethane, (meth)acrylate polymer, polypyrrole, polythiophene, polyoctylthiophene, polyanaline, polyvinyl pyrrolidone, agarose, hydrogel, sol-gel materials, and combinations thereof.

19. The electrochemical sensor device according to claim 15, wherein the water immiscible organic solvent comprises 2-nitrophenyl octyl ether (o-NPOE), dioctyl sebacate (DOS), bis(2-ethylhexyl)sebacate, benzyl s-nitrophenyl ether, bis(1-butilpentyl) adipate, bis(2-ethylhexyl) adipate, bis(2-ethylhexyl) phthalate, 1-chloronaphthalene, chloroparaffin, 1-decanol, dibutyl phthalate, dibutyl sebacate, dibutyl-dilaurate, dodecyl 2-nitrophenyl ether, or combinations thereof.

20. The electrochemical sensor device according to claim 15, wherein the charge transfer component is tetradecylammonium tetrakis(pentofluorophenyl)borate (TDATPFPB), tetrahexylammonium perchlorate, or a combination thereof.

21. The electrochemical sensor device according to claim 15, wherein the coating comprises PVC, o-NPOE, and TDATPFPB.

22. The electrochemical sensor device according to claim 15, wherein the coating is less than about 200 μ

m thick.

72. A target-controlled infusion drug delivery device comprising:

a drug reservoir;

a pump in communication with the drug reservoir;

an electrochemical sensor device according to claim 15; and

a control system that receives an output of the electrochemical sensor device upon detection of the bio available drug concentration in a fluid sample and controls operation of the pump based on the detected concentration of bioavailable drug.

73. The device according to claim 72, wherein the drug is selected from the group of anesthetics, barbiturates, and sedatives.

74. The device according to claim 73, wherein the drug is selected from the group consisting of Propofol, medasolam, methohexitol, atomedate and sufentanol.

75. The device according to claim 72, wherein the control system measures the output of the electrochemical sensor device and modifies operation of the pump in real-time based on the measured output.

76. A catheter comprising:

a body and a lumen, and an electrochemical sensor device according to claim 15 in communication with the lumen or externally of the body, wherein the coating is capable of partitioning a bioavailable drug directly from a body fluid.

77. A micro fluidic device comprising a microfluid channel and an electrochemical sensor device according to claim 15 in communication with the micro fluid channel.

78. A method of modulating drug delivery comprising:

exposing a fluid sample obtained from a patient to an electrochemical sensor device according to claim 15;

detecting an oxidation/reduction current within the coating during said exposing, wherein the detected current relates to a concentration of bioavailable drug in the fluid sample; and

modulating delivery of the drug into a patient based on the concentration of the bioavailable drug in the fluid sample.

79. The method according to claim 78, wherein said detecting is repeated.

80. The method according to claim 79, wherein the repetition of said detecting is carried out at a frequency of at least every 5 minutes.

81. The method according to claim 79, wherein said modulating is carried out if the bioavailable drug concentration in the fluid sample is less than a first threshold value or greater than a second threshold value.

82. The method according to claim 78, wherein said modulating is carried out in real-time based on said detecting.

83. A method for electrochemical detection of bioavailable drug concentration in a fluid sample, the method comprising:

exposing a fluid sample to an electrochemical sensor device according to claim 15; and

detecting an oxidation/reduction current within the coating during said exposing, wherein the detected current relates to the concentration of bioavailable drug in the fluid sample.

23-71. -71. (canceled)