Multi-modal drug delivery system

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/cm 2 .

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/cm 2 .

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/cm 2 .

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.