Electronic card for transdermal drug delivery and analyte extraction

• US 20020038101A1
• Filed: 05/17/2001
• Published: 03/28/2002
• Est. Priority Date: 11/09/1998
• Status: Active Grant

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: TransPharma Medical Ltd. (Syneron Incorporated)
• Inventors: Gross, Yossi, Avrahami, Zohar, Sohn, Ze?apos;ev
• Granted Patent: US 6,597,946 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/0428 Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428

Abstract

Devices for facilitating transdermal passage of materials are provided. In a preferred embodiment, a device for delivering a substance to skin of a subject is provided. A substance storage unit is adapted to store the substance. An analysis unit is adapted to receive a portion of a body fluid of the subject, to analyze the portion, and to generate a signal responsive to the analysis of the portion, One or more electrodes are adapted to be placed at respective sites on the skin. A substance delivery unit is adapted to receive the signal, and, responsive thereto, to drive at least some of the one or more electrodes to apply to respective ones of the sites on the skin a current capable of ablating stratum corneum epidermidis of the skin, so as to facilitate delivery of the substance from the storage unit through the skin at the respective ones of the sites.

Claims

1. A device for delivering a substance to skin of a subject, comprising:

a substance storage unit, which is adapted to store the substance;

a sensor, which is adapted to generate a sensor signal responsive to a physiological parameter of the subject;

one or more electrodes, which are adapted to be placed at respective sites on the skin; and

a substance delivery unit, which is adapted to receive the signal, and, responsive thereto, to drive at least some of the one or more electrodes to apply to respective ones of the sites on the skin a current capable of ablating stratum corneum epidermidis of the skin, so as to facilitate delivery of the substance from the storage unit through the skin at the respective ones of the sites.

2. A device according to claim 1, wherein the sensor comprises an analysis unit, which is adapted to receive a portion of a body fluid of the subject, to analyze the portion, and to generate the sensor signal responsive to the analysis of the portion.

3. A device according to claim 2, wherein the analysis unit is adapted to drive at least one of the one or more electrodes to apply a substantially DC current to the skin so as to enhance by means of iontophoresis extraction through the skin of the portion of the body fluid.

4. A device according to claim 2, wherein the analysis unit is adapted to analyze the portion of the body fluid to determine a level of sugar in blood of the subject, and to generate the signal responsive thereto.

5. A device according to claim 4, wherein the substance storage unit is adapted to store insulin.

6. A device according to claim 1, wherein the substance delivery unit is adapted:

to designate at a first time a first number of the one or more electrodes to drive to apply the current, responsive to a desired rate of delivery of the substance during a first time period, and

to designate at a second time a second number of the one or more electrodes to drive to apply the current, responsive to a desired rate of delivery of the substance during a second time period, the second number being different from the first number.

7. A device according to claim 1, wherein the substance delivery unit is adapted to:

drive a first subset of the one or more electrodes to apply during a first time period, a current capable of ablating stratum corneum in a vicinity of the first subset of the one or more electrodes, and

drive a second subset of the one or more electrodes to apply, during a second time period, a current capable of ablating stratum corneum in a vicinity of the second subset,

wherein the second subset comprises at least one electrode which is not in the first subset.

8. A device according to claim 1, wherein the substance delivery unit is adapted to drive a subset of the one or more electrodes to apply:

during a first time period, a current capable of ablating stratum corneum in a vicinity of the subset of the one or more electrodes, and

during a second time period, a current capable of ablating stratum corneum in the vicinity.

9. A device according to claim 8, wherein the sensor is adapted to measure a property of skin in the vicinity.

10. A device according to claim 1, wherein at least one of the one or more electrodes is adapted to apply to the skin a substantially DC current capable of enhancing by means of iontophoresis the passage of a material through the skin.

11. A device according to claim 10, wherein the substance delivery unit is adapted to drive the at least one of the one or more electrodes to apply the substantially DC current to the skin so as to enhance by means of iontophoresis the delivery of the substance through the skin.

12. A device according to claim 1, and comprising a transport facilitation unit, adapted to facilitate transport of a material through the skin.

13. A device according to claim 1, wherein the device comprises a communications unit, which is adapted to receive the signal and, responsive thereto, to transmit information to a computer external to the device.

14. A device according to claim 1, wherein the device comprises a communications unit, which is adapted to receive an instruction from a remote computer, and wherein the substance delivery unit is adapted to modify, responsive to the instruction, a parameter of the current.

15. A device according to claim 1, wherein the sensor comprises an analysis unit which is adapted to drive a subset of the one or more electrodes to apply a current to the skin, so as to facilitate extraction therefrom of an analyte in a body fluid of the subject.

16. A device according to claim 15, wherein the analysis unit is adapted to drive the subset of the one or more electrodes to apply a current to the skin capable of ablating stratum corneum epidermidis of the skin.

17. A device according to claim 1, wherein the sensor comprises an analysis unit which is adapted to analyze at least one of:

blood of the subject, urine of the subject, and saliva of the subject, and to generate the signal responsive thereto.

19. A device according to claim 18, and comprising a transport facilitation unit, adapted to facilitate transport of a material through the skin.

20. A device according to claim 18, wherein the analysis unit is adapted to drive the first subset of the set of electrodes to apply a substantially DC current to the skin, to enhance by means of iontophoresis the extraction of the analyte through the skin.

21. A device according to claim 18, wherein the substance delivery unit is adapted to drive the second subset of the set of electrodes to apply a substantially DC current to the skin to enhance by means of iontophoresis the delivery of the substance through the skin.

22. A device according to claim 18, wherein the device comprises a communications unit, which is adapted to receive the signal and, responsive thereto, to transmit information to a computer external to the device.

23. A device according to claim 18, wherein the device comprises a communications unit, which is adapted to receive an instruction from a remote computer, and wherein the substance delivery unit is adapted to modify, responsive to the instruction, a parameter of the current delivered through the second subset of the set of electrodes.

24. A device according to claim 18, wherein the first subset of electrodes comprises at least one electrode in the second subset of electrodes.

25. A device according to claim 18, wherein the first subset of electrodes consists exclusively of electrodes which are not in the second subset of electrodes.

28. A device according to claim 27, and comprising a transport facilitation unit, adapted to facilitate transport of the portion through the skin.

29. A device according to claim 27, and comprising a transport facilitation unit, adapted to facilitate transport of one of the substances through the skin.

30. A device according to claim 27, wherein the material delivery unit is adapted to drive the one or more electrodes to apply the current at a level sufficient to ablate stratum corneum epidermidis of the skin.

31. A device according to claim 27, wherein the material delivery unit is adapted to configure the current, responsive to the signal, so as to facilitate delivery of the material stored in one of the regions, while substantially not facilitating the delivery of the material stored in another one of the regions.

68. A device according to claim 1, wherein the sensor is adapted to measure a physiological parameter selected from the list consisting of:

transepidermal water loss (TEWL), a property of the skin, temperature, blood pressure, heart rate, and respiration rate.

18. A device for delivering a substance to skin of a subject, comprising:

a housing;

a set of electrodes, fixed to the housing, which set of electrodes is adapted to be placed at respective sites on the skin;

an analysis unit, fixed to the housing, which analysis unit is adapted to drive a first subset of the set of electrodes to apply a current to the skin so as to facilitate extraction therefrom of an analyte, to analyze the analyte, and to generate a signal responsive to the analysis of the analyte;

a substance storage unit, fixed to the housing, which storage unit is adapted to store the substance; and

a substance delivery unit, fixed to the housing, which delivery unit is adapted to receive the signal, and, responsive thereto, to drive a second subset of the set of electrodes to apply current to the skin so as to facilitate delivery of the substance from the storage unit through the skin.

26. A device for analyzing an analyte extracted through skin of a subject, comprising:

one or more electrodes, which are adapted to be placed at respective sites on the skin;

a control unit, which is adapted to drive the one or more electrodes to apply a current to the respective sites on the skin capable of ablating stratum corneum epidermidis of the skin, so as to facilitate extraction of the analyte through the skin;

an analysis unit, which is adapted to analyze the analyte and to generate a signal responsive to the analysis of the analyte; and

a communications unit, which is adapted to receive the signal and, responsive thereto, to transmit information to a computer external to the device.

27. A device for regulating a substance in the body of a subject, comprising;

an analysis unit, which is adapted to receive a portion of a body fluid of the subject, to analyze the portion, and to generate a signal, responsive to an actual level of the substance in the portion;

a material storage unit, which is adapted to store two or more different material in respective regions of the material storage unit;

one or more electrodes, which are adapted to be placed at respective sites on the skin; and

a material delivery unit, which is adapted to receive the signal, and, responsive thereto, to drive the one or more electrodes to apply current to the respective sites on the skin capable of facilitating delivery of one or more of the materials from the storage unit through the skin at the respective sites, so as to maintain a desired level of the substance in the body of the subject.

32. A device for analyzing an analyte extracted through skin of a subject, comprising:

a housing;

one or more electrodes, fixed to the housing, which one or more electrodes are adapted to be placed at respective sites on the skin;

a control unit, fixed to the housing, which control unit is adapted to drive at least some of the one or more electrodes to apply a current to the respective sites on the skin capable of ablating stratum corneum epidermidis of the skin, so as to facilitate extraction of the analyte through the skin; and

an analysis unit, fixed to the housing, which is adapted to analyze the analyte and to generate a signal responsive to the analysis of the analyte.

33. A device according to claim 32, wherein the control unit is adapted:

to designate at a first time a first number of the one or more electrodes to drive to apply the current, responsive to a desired extraction rate of the analyte during a first time period, and

to designate at a second time a second number of the one or more electrodes to drive to apply the current, responsive to a desired extraction rate of the analyte during a second time period, the second number being different from the first number.

34. A device according to claim 32, wherein the control unit is adapted to drive the at least some of the one or more electrodes to apply a substantially DC current to the skin, to enhance by means of iontophoresis the extraction of the analyte through the skin.

35. A device according to claim 32, wherein the control unit is adapted to:

drive a first subset of the one or more electrodes to apply, during a first time period, a current capable of ablating stratum corneum in a vicinity of the first subset of the one or more electrodes, and

drive a second subset of the one or more electrodes to apply, during a second time period, a current capable of ablating stratum corneum in a vicinity of the second subset,

wherein the second subset comprises at least one electrode which is not in the first subset.

36. A device according to claim 35, and comprising a sensor, adapted to measure a physiological parameter of the subject and to generate a sensor signal responsive thereto, wherein the control unit is adapted to designate the first and second times responsive to the sensor signal.

37. A device according to claim 32, wherein the control unit is adapted to drive a subset of the one or more electrodes to apply:

during a first time period, a current capable of ablating stratum corneum in a vicinity of the subset of the one or more electrodes, and

during a second time period, a current capable of ablating stratum corneum in the vicinity.

38. A device according to claim 32, and comprising a sensor, adapted to measure a physiological parameter of the subject and to generate a sensor signal responsive thereto, wherein the control unit is adapted to drive the at least some of the one or more electrodes to apply the current responsive to the sensor signal.

39. A device according to claim 38, wherein the sensor is adapted to measure a physiological parameter selected from the list consisting of:

transepidermal water loss (TEWL), a property of the skin, temperature, blood pressure, heart rate, and respiration rate.

40. A device according to claim 32, and comprising:

a substance storage unit, which is adapted to store a substance; and

a substance delivery unit, which is adapted to receive the signal generated by the analysis unit, and, responsive thereto, to drive a subset of the one or more electrodes to apply a substance-delivery-unit current to respective ones of the sites on the skin so as to facilitate delivery of the substance from the storage unit through the skin at the respective ones of the sites.

41. A device according to claim 40, wherein the substance delivery unit is adapted to drive the subset of the one or more electrodes to apply a substantially DC current to the skin to enhance by means of iontophoresis the delivery of the substance through the skin.

42. A device according to claim 40, and comprising a sensor, adapted to measure a physiological parameter of the subject and to generate a sensor signal responsive thereto, wherein the substance delivery unit is adapted to configure the substance-delivery-unit current responsive to the sensor signal.

43. A method for delivering a substance to skin of a subject, comprising;

sensing a physiological parameter of the subject;

analyzing the parameter; and

responsive to the analysis of the parameter, applying to the skin a current capable of ablating stratum corneum epidermidis of the skin, so as to facilitate delivery of the substance into the skin.

44. A method for analyzing an analyte extracted through skin of a subject, comprising:

applying to the skin a current capable of ablating stratum corneum epidermidis of the skin, so as to facilitate extraction of the analyte through the skin;

analyzing the analyte in a device that is attached by the subject to the skin; and

responsive to the analysis, transmitting information to a computer external to the device.

47. A device according to claim 46, wherein the transport facilitation unit comprises a pressure generation unit, which is adapted to generate a pressure in a vicinity of the skin capable of facilitating the transport of the substance through the skin.

48. A device according to claim 47, and comprising a storage unit, adapted to store the substance, wherein the pressure generation unit is adapted to generate a positive pressure capable of facilitating the delivery of the substance from the storage unit through the skin.

49. A device according to claim 47, wherein the pressure generation unit is adapted to generate a negative pressure capable of facilitating extraction of the substance through the skin.

50. A device according to claim 46, wherein the transport facilitation unit comprises a mechanical vibration unit, which is adapted to generate vibrations in the skin capable of facilitating the transport of the substance through the skin.

51. A device according to claim 50, and comprising a storage unit, adapted to store the substance, wherein the mechanical vibration unit is adapted to generate vibrations capable of facilitating delivery of the substance from the storage unit through the skin.

52. A device according to claim 50, wherein the mechanical vibration unit is adapted to generate vibrations capable of facilitating extraction of the substance through the skin.

53. A device according to claim 46, wherein the transport facilitation unit comprises an ultrasound generation unit, which is adapted to generate ultrasound waves in a vicinity of the skin capable of facilitating transport of the substance through the skin.

54. A device according to claim 53, and comprising a storage unit, adapted to store the substance, wherein the ultrasound generation unit is adapted to generate the ultrasound waves so as to facilitate delivery of the substance from the storage unit through the skin.

55. A device according to claim 53, wherein the ultrasound generation unit is adapted to generate the ultrasound waves so as to facilitate extraction of the portion of the body fluid through the skin.

57. A device according to claim 56, wherein the control unit is adapted to drive the current as an alternating current (AC).

58. A device according to claim 57, wherein the control unit is adapted to configure a frequency of the current to be between about 1 kHz and about 300 kHz.

59. A device according to claim 56, wherein the control unit is adapted to drive the current that is capable of causing ablation during a first time period, so as to facilitate passage of the substance through an ablated area of the stratum corneum during a second time period, subsequent to the first time period.

45. A method for regulating a substance in the body of a subject, comprising:

storing two or more different materials in respective regions of a material storage unit;

sensing a physiological parameter of the subject;

analyzing the parameter to obtain an indication of an actual level of the substance in the body of the subject;

selecting a material from the two or more materials, responsive to the analysis; and

applying to skin of the subject a current capable of facilitating delivery of the selected material from the storage unit into the skin, so as to maintain a desired level of the substance in the body of the subject.

46. A device for facilitating transdermal passage of a substance through skin of a subject, comprising:

one or more electrodes, which are adapted to be placed at respective sites on the skin;

a control unit, which is adapted to drive at least some of the one or more electrodes to apply to respective ones of the sites on the skin a current capable of ablating stratum corneum epidermidis of the skin; and

a transport facilitation unit, adapted to facilitate transdermal passage of the substance through an ablated region of the stratum corneum.

56. A device for facilitating transdermal passage of a substance through skin of a subject, comprising:

one or more electrodes, which are adapted to be placed at respective sites on the skin; and

a control unit, which is adapted;

to drive at least some of the one or more electrodes to apply to respective ones of the sites on the skin a current capable of ablating stratum corneum epidermidis of the skin, so as to facilitate transdermal passage of the substance through the skin,

to designate at a first time a first number of the one or more electrodes to drive to apply the current, responsive to a desired rate of passage of the substance during a first time period, and

to designate at a second time a second number of the one or more electrodes to drive to apply the current, responsive to a desired rate of passage of the substance during a second time period, the second number being different from the first number.

60. A device for facilitating transdermal passage of a substance through skin of a subject, comprising:

one or more electrodes, which are adapted to be placed at respective sites on the skin; and

a control unit, which is adapted;

to drive a first subset of the one or more electrodes to apply during a first time period, a current capable of ablating stratum corneum in a vicinity of the first subset of the one or more electrodes, so as to facilitate transdermal passage of the substance through the skin, and

to drive a second subset of the one or more electrodes to apply, during a second time period, a current capable of ablating stratum corneum in a vicinity of the second subset, so as to facilitate transdermal passage of the substance through the skin,

wherein the second subset comprises at least one electrode which is not in the first subset.

61. A device according to claim 60, wherein the control unit is adapted to configure the current during the first time period as an alternating current (AC).

62. A device according to claim 61, wherein the control unit is adapted to configure a frequency of the alternating current to be between about 1 kHz and about 300 kHz.

63. A device according to claim 60, wherein the control unit is adapted to drive the current that is capable of causing ablation during the first time period, so as to facilitate passage of the substance through an ablated area of the stratum corneum during a substance-passage time period subsequent to the first time period.

64. A device for facilitating transdermal passage of a substance through skin of a subject, comprising:

one or more electrodes, which are adapted to be placed at respective sites on the skin; and

a control unit, which is adapted to drive a subset of the one or more electrodes to apply;

during a first time period, a current capable of ablating stratum corneum in a vicinity of the subset of the one or more electrodes, and

during a second time period, a current capable of ablating stratum corneum in the vicinity of the subset of the one or more electrodes.

65. A device according to claim 64, wherein the control unit is adapted to configure the current during the first time period as an alternating current (AC).

66. A device according to claim 65, wherein the control unit is adapted to configure a frequency of the alternating current to be between about 1 kHz and about 300 kHz.

67. A device according to claim 64, wherein the control unit is adapted to drive the current during the first time period, so as to facilitate passage of the substance through an ablated area of the stratum corneum during a substance-passage time period subsequent to the first time period.