Multi-modal drug delivery system

• US 8,523,791 B2
• Filed: 08/11/2009
• Issued: 09/03/2013
• Est. Priority Date: 08/11/2009
• Status: Active Grant

• Current Assignee: CareWear Corp.
• Original Assignee: Laboratoire Naturel Paris, LLC
• Inventors: Castel, J. Chris
• Primary Examiner(s): Brown, Michael A.
• Application Number:
  US12/539,270
• Publication Number:
  US 20110040235A1
• Time in Patent Office: 1,484 Days
• Field of Search: 601/15, 601/46, 604/113, 607/3, 607/2
• US Class Current: 601/15
• CPC Class Codes: A61F 2007/0075 using a Peltier element, e.g. near the spot to be heated or cooled
• CPC Class Codes: A61F 2007/0087 Hand-held applicators
• CPC Class Codes: A61F 2007/0096 with a thermometer
• CPC Class Codes: A61F 7/00 Heating or cooling appliances for medical or therapeutic treatment of the human body heating or cooling means in connection with bedsteads or mattresses A47C21/00 ; massage, therapeutic baths A61H; hyperthermia using electric or magnetic fields or ultrasound A61N; electric heating elements H05B
• CPC Class Codes: A61H 2201/0228 heated by an electric resistance element
• CPC Class Codes: A61H 2201/0285 with Peltier elements
• CPC Class Codes: A61H 2201/10 with further special therapeutic means, e.g. electrotherapy, magneto therapy or radiation therapy, chromo therapy, infrared or ultraviolet therapy
• CPC Class Codes: A61H 2201/105 with means for delivering media, e.g. drugs or cosmetics
• CPC Class Codes: A61H 2201/5038 freely programmable by the user
• CPC Class Codes: A61H 2201/5082 Temperature sensors
• CPC Class Codes: A61H 2230/50 Temperature
• CPC Class Codes: A61H 23/0245 with ultrasonic transducers, e.g. piezoelectric
• CPC Class Codes: A61H 23/0263 using rotating unbalanced masses
• CPC Class Codes: A61H 7/005 hand-held
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61N 2005/0629 Sequential activation of light sources
• CPC Class Codes: A61N 2005/063 comprising light transmitting means, e.g. optical fibres
• CPC Class Codes: A61N 2005/0644 Handheld applicators
• CPC Class Codes: A61N 2005/0652 Arrays of diodes
• CPC Class Codes: A61N 2005/0659 : infrared
• CPC Class Codes: A61N 5/0616 : Skin treatment other than tanning
• CPC Class Codes: A61N 5/067 : using laser light

Abstract

A device for the transdermal delivery of a therapeutic agent at a treatment site comprising a housing containing: a mechanical vibration element; a light source; a heating and/or cooling element; a power source for powering said mechanical vibrational element, light source, and heating element; and an electronic control module.

Claims

1. A device for the transdermal delivery of a therapeutic agent to the skin at a treatment site comprising a housing containing:

a mechanical vibration element, wherein said mechanical vibration element is selected from the group consisting of (a) a mechanical vibration element which produces mechanical energy having a frequency of about 15 kHz to 100 kHz;

(b) a mechanical vibration element which produces mechanical energy having a frequency of about 100 kHz to 5 MHz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz; and

(c) a mechanical vibration element which produces mechanical energy having a frequency of about 10 Hz to 1000 Hz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz;

a light source;

a heating and/or cooling element;

a power source for powering said mechanical vibrational element, light source, and heating and/or cooling element; and

an electronic control module for controlling said mechanical vibrational element, light source, and heating and/or cooling element.

2. The device of claim 1 wherein said mechanical vibrational element, light source, and heating and/or cooling element are positioned within an injection molded housing.

3. The device of claim 2 further comprising a reservoir in said housing, said reservoir having a therapeutic composition therein.

4. The device of claim 3 further wherein said therapeutic composition comprises a therapeutically effective amount of ascorbic acid or its pharmaceutically acceptable salts and esters.

5. The device of claim 1 wherein said mechanical vibration element comprises an ultrasonic transducer having an operating frequency of between about 15 kHz and 35 kHz.

6. The device of claim 1 wherein said mechanical vibration element produces mechanical energy having a frequency of about 100 kHz to 5 MHz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz.

7. The device of claim 6 wherein said light source produces light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said mechanical energy modulation frequency.

8. The device of claim 1 wherein said mechanical vibration element produces mechanical energy having a frequency of about 10 Hz to 1000 Hz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz.

9. The device of claim 8 wherein said light source produces light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said mechanical energy modulation frequency.

10. The device of claim 6 wherein said mechanical vibration element provides said modulation at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

11. The device of claim 10 where said mechanical vibration element provides said modulation at a third modulation frequency for a third period of time.

12. The device of claim 8 wherein said mechanical vibration element provides said modulation at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

13. The device of claim 12 where said mechanical vibration element provides said modulation at a third modulation frequency for a third period of time.

14. The device of claim 6 wherein light source is modulated synchronously with the mechanical vibration element, and said modulation is at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

15. The device of claim 14 where said mechanical vibration element and said light source provides said modulation at a third modulation frequency for a third period of time.

16. The device of claim 1 wherein said mechanical vibration element comprises an ultrasonic transducer which produces ultrasound having a frequency of about 100 kHz to 5 MHz modulated with an ultrasonic frequency of about 15 kHz and 100 kHz.

17. The device of claim 16 wherein said light source produces light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said ultrasonic modulation frequency.

18. The device of claim 1 wherein said mechanical vibration element is selected from the group consisting of an ultrasonic transducer, motor having an offset cam, buzzer, voice coil, and magnetic transducer.

19. The device of claim 1 wherein said light source comprises a plurality of light emitting diodes or lasers having a wavelength between about 600 and 1650 nm.

20. The device of claim 1 wherein said heating and/or cooling element comprises a Peltier element.

21. The device of claim 1 wherein said mechanical vibration element comprises an ultrasonic transducer having a frequency between about 15 kHz and 100 kHz, said light source comprises a plurality of light emitting diodes having a wavelength between about 600 nm and 1650 nm, and said heating and/or cooling element comprises a Peltier element, and further comprising a reservoir in said housing, and reservoir having a therapeutic composition comprising about 2 wt % to 35 wt % ascorbic acid or its pharmaceutically acceptable salts and esters.

22. The device of claim 21 further comprising a piston having a piston head positioned in said reservoir and adapted to dispense said therapeutic composition from said housing.

23. The device of claim 21 wherein said therapeutic composition is contained in a replaceable cartridge or pouch in said reservoir.

24. The device of claim 23 wherein said replaceable cartridge or pouch has a frangible seal.

25. The device of claim 1 wherein said a mechanical vibration element comprises an ultrasonic transducer and said light source comprises a light ring, said light ring being positioned annularly around said ultrasonic transducer.

26. The device of claim 1 wherein said mechanical vibration element comprises an ultrasonic transducer and said heating and/or cooling element comprises a Peltier element, wherein said Peltier element is positioned annularly around said ultrasonic transducer.

27. The device of claim 1 wherein said light source comprises a laser having a wavelength between about 600 nm and 1650 nm which generates light energy pulsed at laser modulation frequency between about 15 kHz and 100 kHz.

28. The device of claim 27 wherein said light source further comprises a light emitting diode, and light energy generated by said light emitting diode is superimposed with said light energy from said laser.

29. The device of claim 1 wherein said housing has a patterned etched cap assembly for allowing light from said light source to be applied to said treatment site in a pre-determined pattern.

30. The device of claim 1 further comprising an audible or visual alert for alerting a user that a treatment time has been met.

31. A kit comprising the device of claim 1 and a container having a therapeutic composition housed therein.

32. A method for transdermally delivering a therapeutic agent to a patient'"'"'s treatment site on the skin comprising:

(a) decreasing the temperature of the treatment site by cooling the treatment site;

(b) applying mechanical energy the treatment site, said mechanical energy having a frequency selected from the group consisting of (i) a frequency of about 15 kHz to 100 kHz;

(ii) a frequency of about 100 kHz to 5 MHz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz; and

(iii) a frequency of about 10 Hz to 1000 Hz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz;

(c) applying light energy to said treatment site; and

(d) applying a composition comprising a therapeutically effective amount of said therapeutic agent.

33. The method of claim 32 wherein steps (a), (b), (c), and (d) are performed simultaneously.

34. The method of claim 32 wherein said applying mechanical energy step comprises applying mechanical energy having a frequency of about 100 kHz to 5 MHz modulated with mechanical energy having a frequency of about 15 kHz and 100 kHz.

35. The method of claim 34 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said mechanical energy modulation frequency.

36. The method of claim 32 wherein said applying mechanical energy step comprises applying said mechanical energy at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

37. The method of claim 32 wherein said light energy is modulated synchronously with said mechanical energy and said modulation is at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

38. The method of claim 37 wherein said light energy and said mechanical energy are modulated at a third modulation frequency for a third period of time.

39. The method of claim 32 wherein said applying mechanical energy step comprises applying mechanical energy having a frequency of about 10 Hz to 1000 Hz modulated with a mechanical energy having a frequency of about 15 kHz to 100 kHz.

40. The method of claim 39 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said mechanical energy modulation frequency.

41. The method of claim 32 wherein said applying mechanical energy step comprises applying ultrasound having a frequency of about 100 kHz to 5 MHz modulated with a ultrasonic modulation frequency of about 15 kHz to 100 kHz.

42. The method of claim 41 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said ultrasonic modulation frequency.

43. The method of claim 32 where said light energy is provided by a light emitting diode or scanning laser.

44. The method claim 32 wherein said light energy has a wavelength between 600 nm and 650 nm and an energy density of about 1 to 20 J/cm².

45. The method of claim 32 wherein said mechanical energy is provided by an ultrasonic transducer, motor having an offset cam, voice coil, buzzer, or magnetic transducer.

46. The method of claim 32 wherein said therapeutic agent is ascorbic acid or its pharmaceutically acceptable salts and esters.

47. The method of claim 32 wherein said light energy is applied at a level that does not change the treatment site temperature.

48. The method of claim 32 further comprising a second therapeutic agent in said composition, and wherein said mechanical energy is applied at a first frequency associated with delivery of said therapeutic agent to said treatment site, and said mechanical energy is then applied at a second frequency associated with delivery of said second therapeutic agent to said treatment site, and wherein said first frequency and said second frequency are different.

49. The method of claim 48 wherein said first frequency and said second frequency are determined by microdialysis of said first therapeutic agent and said second therapeutic agent.

50. The method of claim 48 wherein said mechanical energy is modulated and wherein said light energy is modulated synchronously with said mechanical energy and said modulation is at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

51. The method of claim 50 wherein said light energy and said mechanical energy are modulated at a third modulation frequency for a third period of time.

52. A method for transdermally delivering a therapeutic agent to a patient'"'"'s treatment site on the skin comprising:

(a) increasing the temperature of the treatment site by heating the treatment site by about 0.5 to 2°

C.;

(b) applying mechanical energy the treatment site, said mechanical energy having a frequency selected from the group consisting of (i) a frequency of about 15 kHz to 100 kHz;

(ii) a frequency of about 100 kHz to 5 MHz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz; and

(iii) having a frequency of about 10 Hz to 1000 Hz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz;

(c) applying light energy to said treatment site; and

(d) applying a composition comprising a therapeutically effective amount of said therapeutic agent to the treatment site.

53. The method of claim 52 wherein steps (a), (b), (c), and (d) are performed simultaneously.

54. The method of claim 52 wherein said applying mechanical energy step comprises applying mechanical energy having a frequency of about 100 kHz to 5 MHz modulated with mechanical energy having a frequency of about 15 kHz and 100 kHz.

55. The method of claim 54 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said mechanical energy modulation frequency.

56. The method of claim 52 wherein said applying mechanical energy step comprises applying said mechanical energy at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

57. The method of claim 52 wherein said light energy is modulated synchronously with said mechanical energy and said modulation is at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

58. The method of claim 57 wherein said light energy and said mechanical energy are modulated at a third modulation frequency for a third period of time.

59. The method of claim 52 wherein said applying mechanical energy step comprises applying mechanical energy having a frequency of about 10 Hz to 1000 Hz modulated with a mechanical energy having a frequency of about 15 kHz to 100 kHz.

60. The method of claim 59 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said mechanical energy modulation frequency.

61. The method of claim 52 wherein said applying mechanical energy step comprises applying ultrasound having a frequency of about 100 kHz to 5 MHz modulated with a ultrasonic modulation frequency of about 15 kHz and 100 kHz.

62. The method of claim 61 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said ultrasonic modulation frequency.

63. The method of claim 52 where said light energy is provided by a light emitting diode or scanning laser.

64. The method claim 52 wherein said light energy has a wavelength between about 600 nm and 650 nm and an energy density of about 1 to 20 J/cm².

65. The method of claim 52 wherein said mechanical energy is provided by an ultrasonic transducer, motor having an offset cam, voice coil, buzzer, or magnetic transducer.

66. The method of claim 52 wherein said therapeutic agent is ascorbic acid or its pharmaceutically acceptable salts and esters.

67. The method of claim 52 wherein said light energy is applied at a level that causes the increase in temperature from about 0.5 to 2°

C. at the treatment site.

68. The method of claim 52 further comprising a second therapeutic agent in said composition, and wherein said mechanical energy is applied at a first frequency associated with delivery of said therapeutic agent to said treatment site, and said mechanical energy is then applied at a second frequency associated with delivery of said second therapeutic agent to said treatment site, and wherein said first frequency and said second frequency are different.

69. The method of claim 68 wherein said first frequency and said second frequency are determined by microdialysis of said first therapeutic agent and said second therapeutic agent.

70. The method of claim 68 wherein said mechanical energy is modulated and wherein said light energy is modulated synchronously with said mechanical energy and said modulation is at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

71. The method of claim 70 wherein said light energy and said mechanical energy are modulated at a third modulation frequency for a third period of time.

72. A method for transdermally delivering a therapeutic agent to a patient'"'"'s treatment site on the skin comprising:

(a) increasing the temperature of the treatment site by heating the treatment site by about 2 to 4°

C.;

(b) applying mechanical energy the treatment site, said mechanical energy having a frequency selected from the group consisting of (i) a frequency of about 15 kHz to 100 kHz;

(ii) a frequency of about 100 kHz to 5 MHz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz; and

(iii) a frequency of about 10 Hz to 1000 Hz modulated with mechanical energy having a frequency of about 15 kHz to 100 kHz;

(c) applying light energy to said treatment site; and

(d) applying a composition comprising a therapeutically effective amount of said therapeutic agent to the treatment site.

73. The method of claim 72 wherein steps (a), (b), (c), and (d) are performed simultaneously.

74. The method of claim 72 wherein said applying mechanical energy step comprises applying mechanical energy having a frequency of about 100 kHz to 5 MHz modulated with mechanical energy having a frequency of about 15 kHz and 100 kHz.

75. The method of claim 74 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said mechanical energy modulation frequency.

76. The method of claim 72 wherein said applying mechanical energy step comprises applying said mechanical energy at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

77. The method of claim 72 wherein said light energy is modulated synchronously with said mechanical energy and said modulation is at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

78. The method of claim 77 wherein said light energy and said mechanical energy are modulated at a third modulation frequency for a third period of time.

79. The method of claim 72 wherein said applying mechanical energy step comprises applying mechanical energy having a frequency of about 10 Hz to 1000 Hz modulated with a mechanical energy having a frequency of about 15 kHz to 100 kHz.

80. The method of claim 79 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said mechanical energy modulation frequency.

81. The method of claim 72 wherein said applying mechanical energy step comprises applying ultrasound having a frequency of about 100 kHz to 5 MHz modulated with a ultrasonic modulation frequency of about 15 kHz to 100 kHz.

82. The method of claim 81 wherein said applying light energy step comprises applying light having a wavelength between about 600 nm and 1650 nm and modulated with a light modulation frequency that is synchronized with said ultrasonic modulation frequency.

83. The method of claim 72 where said light energy is provided by a light emitting diode or scanning laser.

84. The method claim 72 wherein said light energy has a wavelength between about 600 nm and 650 nm and an energy density of about 1 to 20 J/cm².

85. The method of claim 72 wherein said mechanical energy is provided by an ultrasonic transducer, motor having an offset cam, voice coil, buzzer, or magnetic transducer.

86. The method of claim 72 wherein said therapeutic agent is ascorbic acid or its pharmaceutically acceptable salts and esters.

87. The method of claim 72 wherein said light energy is applied at a level that causes the increase in temperature from about 0.5 to 2°

C. at the treatment site.

88. The method of claim 72 further comprising a second therapeutic agent in said composition, and wherein said mechanical energy is applied at a first frequency associated with delivery of said therapeutic agent to said treatment site, and said mechanical energy is then applied at a second frequency associated with delivery of said second therapeutic agent to said treatment site, and wherein said first frequency and said second frequency are different.

89. The method of claim 88 wherein said first frequency and said second frequency are determined by microdialysis of said first therapeutic agent and said second therapeutic agent.

90. The method of claim 88 wherein said mechanical energy is modulated and wherein said light energy is modulated synchronously with said mechanical energy and said modulation is at a first modulation frequency for a first period of time followed by a second modulation frequency for a second period of time.

91. The method of claim 90 wherein said light energy and said mechanical energy are modulated at a third modulation frequency for a third period of time.