Transdermal drug delivery device, method of making same and method of using same

• US 20040039343A1
• Filed: 03/11/2003
• Published: 02/26/2004
• Est. Priority Date: 06/08/2000
• Status: Active Grant

• Current Assignee: Smart Technologies Incorporated (Hon Hai Precision Industry Co., Ltd.), MidCap Funding III, LLC, ​Passport Technologies, Inc.
• Original Assignee: Smart Technologies Incorporated (Hon Hai Precision Industry Co., Ltd.)
• Inventors: McRAE, Stuart, Eppstein, Jonathan, Papp, Joseph
• Granted Patent: US 7,141,034 B2
• Time in Patent Office: Days
• US Class Current: 604/200
• 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 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2205/33 Controlling, regulating or measuring
• CPC Class Codes: A61M 2205/3303 Using a biosensor
• CPC Class Codes: A61M 2210/04 Skin
• CPC Class Codes: A61M 2230/20 Blood composition characteristics
• 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 37/0015 by using microneedles
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0476 Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)
• 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
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The invention provides for a transdermal drug delivery device for forming a micropore in a tissue membrane of an animal, comprising:

a) a tissue interface layer comprising:

i) a substrate comprising a woven fabric, the woven fabric comprising structural fibers and electrically conductive fibers interwoven together; and

ii) at least one porator, wherein the porator is located on or within the substrate and is formed by the electrically conductive fibers acting as a heat resistive element;

b) at least one reservoir in communication with the tissue interface layer; and

c) a controller for controlling the formation of the micropore by the at least one porator.

The invention also provides for methods of making and methods of using the same.

Claims

12. A transdermal drug delivery device for forming a micropore in a tissue membrane of an animal, comprising:

a) a tissue interface layer comprising;

i) a substrate; and

ii) at least one porator, wherein said porator is located on or within said substrate and said porator is constructed of a material in which said porator is destroyed upon forming said micropore;

b) at least one reservoir in communication with said tissue interface layer; and

c) a controller for controlling the formation of said micropore by said at least one porator.

13. The transdermal drug delivery device according to claim 12 further comprising a permeant composition stored within said reservoir.

14. The transdermal drug delivery device according to claim 13, wherein said permeant composition is a drug or therapeutically active ingredient.

15. The transdermal drug delivery device according to claim 12 wherein said reservoir contains an analyte obtained from said animal by way of said micropore.

16. The transdermal drug delivery device according to claim 12 wherein said substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

17. The transdermal drug delivery device according to claim 12 wherein said porator is selected from the group consisting of a wire conductor, a deposited conductive material, a machined conductive material, a laser cut conductive material, an adhesive foil, an electroplated material, a screen-printed material and an etched conductive material.

18. The transdermal drug delivery device according to claim 12 wherein said controller applies a stimulus to said porator, said stimulus initiating formation of said pore by said porator and then destroying said porator following formation of said micropore.

19. The transdermal drug delivery device according to claim 18 wherein said stimulus is a thermal pulse.

20. The transdermal drug delivery device according to claim 18 wherein said stimulus is an electrical pulse.

21. The transdermal drug delivery device according to claim 12 wherein said substrate is constructed of a material which undergoes thermal shrinking when exposed to an elevated temperature due to activation of said porator, whereby said thermal shrinking results in a tear in said substrate and destruction of said porator.

22. The transdermal drug delivery device according to claim 21 wherein said material is a heat-shrinkable polymer.

23. The transdermal drug delivery device according to claim 22 wherein said heat-shrinkable polymer is a polyvinyl.

24. The transdermal drug delivery device according to claim 21 wherein said substrate is formed with a flaw from which said tear would form.

25. The transdermal drug delivery device according to claim 21 wherein said tear forms said communication between said reservoir and said tissue interface layer.

26. The transdermal drug delivery device according to claim 12, wherein said substrate further comprises an adhesive layer to bond said poration device to said biological membrane.

27. A transdermal drug delivery device for forming a micropore in a tissue membrane of an animal, comprising:

a) a tissue interface layer comprising;

i) a substrate; and

ii) at least one porator, wherein said porator is located on or within said substrate;

b) at least one reservoir in communication with said tissue interface layer; and

c) a controller for controlling the formation of said micropore by said at least one porator,

wherein said at least one porator is constructed of a heat resistive element which deforms when heated, thereby allowing said heat resistive element to contact said tissue membrane and form said micropore by ablating said tissue membrane.

28. The transdermal drug delivery device according to claim 27 further comprising a permeant composition stored within said reservoir.

29. The transdermal drug delivery device according to claim 28, wherein said permeant composition is a drug or therapeutically active ingredient.

30. The transdermal drug delivery device according to claim 27 wherein said reservoir contains an analyte obtained from said animal by way of said micropore.

31. The transdermal drug delivery device according to claim 27 wherein said substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

32. The transdermal drug delivery device according to claim 27 wherein said controller applies a stimulus to said porator, said stimulus initiating formation of said pore by said deforming said heat resistive element.

33. The transdermal drug delivery device according to claim 27 wherein said porator is selected from the group consisting of a wire conductor, a machined conductive material, a laser cut conductive material, an adhesive foil, an electroplated material, a shape memory alloy material and an etched conductive material.

34. The transdermal drug delivery device according to claim 27 wherein said porator comprises a plurality of heat resistive elements connected in series.

35. The transdermal drug delivery device according to claim 27 wherein said porator comprises a plurality of heat resistive elements connected in parallel.

36. The transdermal drug delivery device according to claim 27, wherein said substrate further comprises an adhesive layer to bond said poration device to said biological membrane.

37. A transdermal drug delivery device for forming a micropore in a tissue membrane of an animal, comprising:

a) a tissue interface layer comprising;

i) a substrate; and

ii) at least one porator, wherein said porator is located on or within said substrate;

b) a plurality of reservoirs in communication with said tissue interface layer; and

c) a controller for controlling the formation of said micropore by said at least one porator.

38. The transdermal drug delivery device according to claim 37 wherein said plurality of reservoirs comprises at least a first reservoir and a second reservoir.

39. The transdermal drug delivery device according to claim 38 wherein said first reservoir contains a permeant composition to be introduced into said tissue membrane following poration of same.

40. The transdermal drug delivery device according to claim 38 wherein said second reservoir contains an analyte extracted from said tissue membrane following poration of same.

41. The transdermal drug delivery device according to claim 38 wherein said first reservoir contains a first drug or therapeutically active agent and said second reservoir contains a second drug or therapeutically active agent.

42. The transdermal drug delivery device according to claim 38 wherein said first reservoir contains a drug or therapeutically active agent and said second reservoir contains an excipient or other biologically safe diluent for reconstituting said drug or therapeutically active agent into a pharmaceutically acceptable delivery system.

43. The transdermal drug delivery device according to claim 37 wherein said porator comprises a plurality of porators, whereby a single porator is associated with a single reservoir.

44. The transdermal drug delivery device according to claim 43 wherein said reservoirs contain a permeant composition for delivery into said membrane by way of said micropores.

45. The transdermal drug delivery device according to claim 43 wherein said reservoirs contain an analyte extracted from said membrane by way of said micropores.

46. The transdermal drug delivery device according to claim 43 further comprising a controller for controlling said porators

47. The transdermal drug delivery device according to claim 37 wherein said substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

48. The transdermal drug delivery device according to claim 37, wherein said substrate further comprises an adhesive layer to bond said poration device to said biological membrane.

49. The transdermal drug delivery device according to claim 37 wherein said at least one porator is selected from the group consisting of a probe element, an electromechanical actuator, a microlancet, an array of micro-needles or lancets, a thermal energy ablator, a sonic energy ablator, a laser ablation system, and a high pressure fluid jet puncturer.

50. The transdermal drug delivery device according to claim 37 wherein said porator is selected from the group consisting of a wire conductor, a machined conductive material, a laser cut conductive material, an adhesive foil, an electroplated material, a shape memory alloy material and an etched conductive material.

51. A method of manufacturing a transdermal drug delivery device comprising the steps of:

a) weaving electrically conductive fibers into a fabric of non-electrically conductive fibers to form an electrically conductive fabric;

b) applying conductive traces to one end of said electrically conductive fabric to form a conductive network;

c) connecting said conductive network with a controller which controls the application of electricity to said conductive network.

52. The method according to claim 51 wherein said non-electrically conductive fibers are made from a material selected from the group consisting of polyester, nylon, mylar, polycarbonate and mixtures thereof.

53. The method according to claim 51 wherein said electrically conductive fibers are made from a material selected from the group consisting of tungsten, tantalum, copper, conductive polymers, glass, carbon fibers and mixtures thereof.

54. The method according to claim 51, further comprising the step of applying an adhesive layer to the bottom of said poration device.

55. The method according to claim 51, wherein said conductive network is in the form of a parallel network.

56. The method according to claim 51, wherein said conductive network is in the form of a series network.

57. The method according to claim 51, wherein said conductive traces are selected from the group consisting of foils, inks, resins, electroplating products and mixtures thereof.

58. The method according to claim 51 further comprising the step of bonding a reservoir to said poration device.

59. A method of manufacturing a transdermal drug delivery device comprising the steps of:

a) providing resistive elements on a frame;

b) placing said frame over a non-conductive substrate;

c) depositing conductive ink onto said substrate and resistive element combination to form a conductive network of poration elements;

d) embossing said conductive network at each of said poration elements; and

e) applying an adhesive layer to said embossed conductive network for facilitating application of said poration device to a tissue membrane.

60. The method according to claim 59 wherein said substrate material is selected from the group consisting of a polyester, a polyamide, and a polycarbonate.

61. The method according to claim 59 wherein said resistive element is selected from the group consisting of copper, tantalum, nitinol, and tungsten.

62. The method according to claim 59 wherein said conductive ink is a silver/polymer ink.

63. The method according to claim 59 wherein said conductive network is formed from a process selected from the group consisting of electro-discharge machining, sputtering, screen-printing, electroplating, micromachining and chemical vapor deposition.

64. A method of forming at least one micropore in a tissue membrane of an animal, comprising:

a) providing a poration device, said poration device including

i) a tissue interface layer comprising;

A) a substrate comprising a woven fabric, said woven fabric comprising structural fibers and electrically conductive fibers interwoven together; and

B) at least one porator, wherein said porator is located on or within said substrate and is formed by said electrically conductive fibers acting as a heat resistive element;

ii) at least one reservoir in communication with said tissue interface layer; and

iii) a controller for controlling the formation of said micropore by said at least one porator;

b) contacting said poration device with said tissue membrane;

c) actuating said poration device to form said at least one micropore in said tissue membrane.

1. A transdermal drug delivery device for forming a micropore in a tissue membrane of an animal, comprising:

a) a tissue interface layer comprising;

i) a substrate comprising a woven fabric, said woven fabric comprising structural fibers and electrically conductive fibers interwoven together; and

ii) at least one porator, wherein said porator is located on or within said substrate and is formed by said electrically conductive fibers acting as a heat resistive element;

b) at least one reservoir in communication with said tissue interface layer; and

c) a controller for controlling the formation of said micropore by said at least one porator.

2. The transdermal drug delivery device according to claim 1 further comprising a permeant composition stored within said reservoir.

3. The transdermal drug delivery device according to claim 2, wherein said permeant composition is a drug or therapeutically active ingredient.

4. The transdermal drug delivery device according to claim 1 wherein said reservoir contains an analyte obtained from said animal by way of said micropore.

5. The transdermal drug delivery device according to claim 1 wherein said structural fibers are made from a material selected from the group consisting of polyester, nylon, mylar, polycarbonate and mixtures thereof.

6. The transdermal drug delivery device according to claim 1 wherein said electrically conductive fibers are made from a material selected from the group consisting of tungsten, tantalum, copper, conductive polymers, glass, carbon fibers and mixtures thereof.

7. The transdermal drug delivery device according to claim 1, wherein said substrate further comprises an adhesive layer to bond said poration device to said biological membrane.

8. The transdermal drug delivery device according to claim 1, wherein said electrically conductive fibers are connected in parallel by conductive traces, thereby forming a conductive network.

9. The transdermal drug delivery device according to claim 8, wherein said conductive traces are selected from the group consisting of foils, inks, resins, electroplating products and mixtures thereof.

10. The transdermal drug delivery device according to claim 1, wherein said electrically conductive fibers are connected in series by conductive traces, thereby forming a conductive network.

11. The transdermal drug delivery device according to claim 10, wherein said conductive traces are selected from the group consisting of foils, inks, resins, electroplating products and mixtures thereof.

65. The method according to claim 64 further comprising the step of applying a permeant composition to said at least one micropore, said permeant composition being stored in said reservoir.

66. The method according to claim 65, wherein said permeant composition is a drug or therapeutically active ingredient.

67. The method according to claim 64 wherein said structural fibers are made from a material selected from the group consisting of polyester, nylon, mylar, polycarbonate and mixtures thereof.

68. The method according to claim 64 wherein said electrically conductive fibers are made from a material selected from the group consisting of tungsten, tantalum, copper, conductive polymers, glass, carbon fibers and mixtures thereof.

69. The method according to claim 64, wherein said substrate further comprises an adhesive layer to bond said poration device to said biological membrane.

70. The method according to claim 64, wherein said electrically conductive fibers are connected in parallel by conductive traces, thereby forming a conductive network.

71. The method according to claim 70, wherein said conductive traces are selected from the group consisting of foils, inks, resins, electroplating products and mixtures thereof.

72. The method according to claim 64, wherein said electrically conductive fibers are connected in series by conductive traces, thereby forming a conductive network.

73. The method according to claim 72, wherein said conductive traces are selected from the group consisting of foils, inks, resins, electroplating products and mixtures thereof.

74. The method according to claim 64 further comprising the step of forming at least one micropore in said reservoir at the same time said at least one micropore in said tissue membrane is being formed.

66-1. The method according to claim 64 wherein said reservoir contains an analyte obtained from said animal by way of said micropore.

75. A method of forming at least one micropore in a tissue membrane of an animal, comprising:

a) providing a poration device, said poration device including;

i) a tissue interface layer comprising;

A) a substrate; and

B) at least one porator, wherein said porator is located on or within said substrate and said porator is constructed of a material in which said porator is destroyed upon forming said micropore;

ii) at least one reservoir in communication with said tissue interface layer; and

iii) a controller for controlling the formation of said micropore by said at least one porator;

b) contacting said poration device with said tissue membrane;

c) providing a thermal or electrical pulse to said at least one porator by way of said controller, thereby forming said at least one micropore in said tissue membrane; and

d) destroying said at least one porator after forming said at least one micropore by sustaining said thermal or electrical pulse for a duration sufficient to destroy said at least one porator.

76. The method according to claim 75 further comprising the step of applying a permeant composition to said at least one micropore, said permeant composition being stored in said reservoir.

77. The method according to claim 76, wherein said permeant composition is a drug or therapeutically active ingredient.

78. The method according to claim 75 wherein said reservoir contains an analyte obtained from said animal by way of said micropore.

79. The method according to claim 75 wherein said substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

80. The method according to claim 75 wherein said porator is selected from the group consisting of a wire conductor, a deposited conductive material, a machined conductive material, a laser cut conductive material, an adhesive foil, an electroplated material, a screen-printed material and an etched conductive material.

81. The method according to claim 75 wherein said substrate is constructed of a material which undergoes thermal shrinking when exposed to an elevated temperature due to activation of said at least one porator, whereby said thermal shrinking results in tearing of said substrate and destruction of said porator.

82. The method according to claim 81 wherein said material is a heat-shrinkable polymer.

83. The method according to claim 82 wherein said heat-shrinkable polymer is a polyvinyl.

84. The method according to claim 81 wherein said substrate is formed with a flaw from which said tear would form.

85. The method according to claim 81 wherein said tear forms said communication between said reservoir and said tissue interface layer.

86. A method of forming at least one micropore in a tissue membrane of an animal, comprising:

a) providing a poration device, said poration device including;

i) a tissue interface layer comprising;

A) a substrate; and

B) at least one porator, wherein said porator is located on or within said substrate and is constructed of a heat resistive element which deforms when heated;

ii) at least one reservoir in communication with said tissue interface layer; and

iii) a controller for controlling the formation of said micropore by said at least one porator;

b) contacting said poration device with said tissue membrane;

c) providing a stimulus to said at least one porator by way of said controller, thereby heating said at least one porator and increasing the length of and deforming same, causing said at least one porator to come into contact with said tissue membrane;

d) forming said at least one micropore; and

e) cooling said at least one porator, thereby decreasing the length of same and returning same to its original shape, resulting in said at least one porator no longer contacting said tissue membrane.

87. The method according to claim 86 further comprising the step of applying a permeant composition to said at least one micropore, said permeant composition being stored in said reservoir.

88. The method according to claim 87, wherein said permeant composition is a drug or therapeutically active ingredient.

89. The method according to claim 86 wherein said reservoir contains an analyte obtained from said animal by way of said micropore.

90. The method according to claim 86 wherein said substrate is selected from the group consisting of a woven material, a film, a supporting layer and a sheet.

91. The method according to claim 86 wherein said porator is selected from the group consisting of a wire conductor, a machined conductive material, a laser cut conductive material, an adhesive foil, an electroplated material, a shape memory alloy material and an etched conductive material.

92. The method according to claim 86 wherein said porator comprises a plurality of heat resistive elements connected in series.

93. The method according to claim 86 wherein said porator comprises a plurality of heat resistive elements connected in parallel.

94. A method of delivering two or more biologically active compounds to a patient in need thereof by way of a tissue membrane, said method comprising the steps of:

a) forming at least one micropore in said tissue membrane by contacting a poration device with said tissue membrane and activating said poration device, thereby forming said at least one micropore;

b) applying a first compound contained in a first reservoir of said poration device to said tissue membrane by way of said at least one micropore; and

c) applying a second compound contained in a second reservoir of said poration device to said tissue membrane by way of said at least one micropore.

95. The method according to claim 94 wherein said first and second compounds are simultaneously applied to said tissue membrane.

96. The method according to claim 94 wherein said first compound is a first biologically active agent and said second compound is a different biologically active agent.

97. The method according to claim 94 wherein said first compound is a biologically active agent and said second compound is a pharmaceutically acceptable excipient.

98. The method according to claim 94 wherein said first and second compounds are mixed within said poration device prior to being applied to said tissue membrane.

99. A method of facilitating passage of biological compounds across a tissue membrane comprising the steps of:

a) forming at least one micropore in said tissue membrane by contacting a poration device with said tissue membrane and activating said poration device, thereby forming said at least one micropore;

b) applying a first compound contained in a first reservoir of said poration device to said tissue membrane by way of said at least one micropore; and

c) extracting a second compound from said tissue membrane and storing said second compound in a second reservoir in said poration device.

100. The method according to claim 99 wherein said steps of applying said first compound to said tissue membrane and extracting said second compound from said tissue membrane are executed simultaneously.

101. The method according to claim 99 wherein said step of extracting said second compound from said tissue membrane is carried out prior to said step of applying said first compound to said tissue membrane.

102. The method according to claim 101 further comprising the step of analyzing said second compound and applying said first compound based on said analysis.