Enhancement of transdermal monitoring applications with ultrasound and chemical enhancers

• US 5,722,397 A
• Filed: 06/06/1995
• Issued: 03/03/1998
• Est. Priority Date: 11/15/1993
• Status: Expired due to Term

• Current Assignee: Nitto Denko Corporation
• Original Assignee: Altea Technologies Inc (Nitto Denko Corporation)
• Inventors: Eppstein, Jonathan A.
• Primary Examiner(s): Cohen, Lee S.
• Assistant Examiner(s): Gilbert, Samuel
• Application Number:
  US08/465,874
• Time in Patent Office: 1,001 Days
• Field of Search: 128/630, 128/632, 128/633, 128/635, 128/636, 128/660.01, 604/20, 604/22, 604/289, 604/290, 604/890.1, 604/892.1, 601/2
• US Class Current: 600/345
• CPC Class Codes: A61B 18/203 applying laser energy to the outside of the body
• CPC Class Codes: A61B 2017/00172 Pulse trains, bursts, intermittent continuous operation
• CPC Class Codes: A61B 2017/00765 Decreasing the barrier function of skin tissue by radiated energy, e.g. using ultrasound, using laser for skin perforation
• CPC Class Codes: A61B 2018/00452 Skin
• CPC Class Codes: A61B 2018/0047 Upper parts of the skin, e.g. skin peeling or treatment of wrinkles
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61K 41/0047 Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
• CPC Class Codes: A61K 49/22 Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

A method of enhancing the permeability of the skin or mucosa to an analyte for diagnostic purposed is described utilizing ultrasound or ultrasound plus a chemical enhancer. If desired the ultrasound may be modulated by means of frequency modulation, amplitude modulation, phase modulation and/or combinations thereof. A frequency modulation from low to high develops a local pressure gradient directed out of the body, thus permitting analytes in the body to traverse the skin and be collected and measured outside the body. The concentration of an analyte in the body is preferably determined by enhancing the permeability of the skin or other biological membrane optionally with a chemical enhancer, applying ultrasound optionally at a modulated frequency, amplitude, phase, or combinations thereof that further induces a local pressure gradient out of the body, collecting the analyte, and utilizing the analyte collection data calculating the concentration of the analyte in the body.

Claims

1. A portable device attachable to a selected area of an individual'"'"'s body surface for monitoring concentrations of an analyte in the body comprising

(a) a collection unit including

(I) reservoir means for holding a chemical permeation enhancer for delivery to the body surface and receiving analyte from the body surface;

(ii) a source optical fiber, couplable to a light source, for conducting light energy therethrough and emitting evanescent wave energy; and

(iii) a detection optical fiber, couplable to a detection device, for capturing and conducting evanescent wave energy, wherein the source and detection optical fibers each have a surface with a binder disposed thereon for binding the analyte; and

(b) an electronic unit releasably coupleted to the collection unit including

(I) an ultrasound transducer for enhancing permeation of the analyte out of the individual'"'"'s body into the reservoir means, the transducer disposed such that when the device is disposed on a selected area of an individual'"'"'s body surface the reservoir is between the body surface and the transducer;

(ii) a power source coupled to the transducer;

(iii) a light source coupled to the power source and releasably coupleted to the source optical fiber for providing light energy to the source optical fiber;

(iv) a detection device releasably coupled to the detection optical fiber for receiving and measuring evanescent wave energy therefrom;

(v) an electronic circuit coupled to the transducer, power source, light source, detection device, and an output device, for controlling the operation of the transducer and light source, receiving measurements of light from the detection device, determining parameters of an equilibrium curve, calculating analyte concentration in the body from the equilibrium curve, and sending a signal containing the analyte concentration to the output device;

(vi) an output device for receiving the signal containing the analyte concentration and displaying the analyte concentration; and

(vii) a cover for enclosing and protecting the transducer, power supply, light source, detection device, electronic circuit, and output device, wherein the cover contains an opening through which the output device displays information.

2. The device of claim 1 wherein the collection unit additionally contains reagents for generating a measurable product, wherein said measurable product can be analyzed to provide a measurement of the analyte.

3. The device of claim 1 wherein said detection device comprises a photosensitive diode.

4. The device of claim 1 wherein said detection device comprises a photomultiplier tube.

5. The device of claim 1 wherein the output device comprises a liquid crystal display.

6. The device of claim 1 wherein the output device comprises a light emitting diode.

7. The device of claim 1 wherein the output device comprises an analog panel meter.

8. The device of claim 1 wherein the binder is an antibody.

9. A portable device attachable to a selected area of an individual'"'"'s body surface for monitoring concentrations of an analyte of interest in the body comprising:

(a) a collection unit including

(I) an optional reservoir for holding a chemical permeation enhancer, and

(ii) a removable reservoir for collection of the analyte of interest; and

(b) an electronic unit including

(I) an ultrasound transducer for enhancing permeation of the analyte through the individual'"'"'s skin and transport out of the individual'"'"'s body, the transducer being placed such that when the device is disposed on a selected area of the individual'"'"'s body surface the enhancer reservoir and collection reservoir are between the body surface and the transducer,

(ii) a power source coupled to the transducer,

(iii) a display for communicating information,

(iv) means for measuring the analyte of interest,

(v) an electronic circuit coupled to the transducer, power source, display, and measuring means for controlling operation of the transducer, operational sequence of the electronic unit, and sending signals to the display to prompt the operator on protocol steps, and

(vi) a cover for enclosing and protecting the transducer, power supply integrated circuit, power source, measuring means, and display.

10. The device of claim 9 wherein the collection unit contains reagents for generating a measurable product, said reagents disposed on a surface that is removable from the electronic unit so that the removable surface may be separated from the electronic unit and the measurable product analyzed to provide a measurement of the analyte of interest.