Device and method for controlled delivery of active substance into the skin

• US 20040267189A1
• Filed: 08/25/2004
• Published: 12/30/2004
• Est. Priority Date: 10/24/2001
• Status: Active Grant

• Current Assignee: Power Flex Ltd.
• Original Assignee: Power Paper Ltd. (Products To Go, Inc.)
• Inventors: Gross, Yossi, Nitzan, Zvi, Tamarkin, Dov, Mavor, Daniela, Arbel, Giora, Harel, Nurit
• Granted Patent: US 7,979,117 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61N 1/044 Shape of the electrode
• 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

An apparatus for dermal treatment of an active substance having certain physical properties comprising a flexible, wearable patch conformable to the contour of a skin surface and having: a first electrode adapted to communicate the active substance into the skin by application of an electrical current on the skin surface, a second electrode, capable of closing electrical circuit with the skin surface, a power source for providing a current and voltage, connected through a conductive media to the first and second electrode, and means for substantially controlling penetration depth of the active substance by selecting at least one variable from a plurality of variables.

Claims

1. An apparatus for dermal and/or topical treatment with a formulation including an active substance and having certain physical properties comprising a flexible, wearable patch conformable to the contour of a skin surface and having:

a first electrode adapted to communicate the active substance into the skin by application of an electrical current on the skin surface,

a second electrode, capable of closing electrical circuit with the skin surface,

a power source for providing a current and voltage, connected through a conductive media to the first and second electrode, and

means for substantially controlling penetration depth of the active substance by selecting at least one variable from a plurality of variables.

2. The apparatus of claim 1, wherein the plurality of variables is selected from the group consisting of voltage, current and current density, concentration of an active substance, pH, viscosity, concentration of a buffer, concentration of an electrolyte, concentration of a polymeric substance which is used to render certain rheological properties, conductivity, viscosity and adhesiveness.

3. The apparatus of claim 101 wherein the plurality of variables includes pore size and pore density of the substrate, current and/or voltage of the power source and physiochemical properties of the active substance such as conductivity.

4. The apparatus of claim 1, wherein the application of the active substance includes delivery of a greater amount of the active substance into the skin than is delivered through the skin.

5. The apparatus of claim 102, wherein the in-vitro skin penetration test system is either the ‘

Dual Chamber In-Vitro Test’

or ‘

Patch-sealed chamber test.’

6. The apparatus of claim 102, wherein the exposure time in the in-vitro skin penetration test system is equivalent to the time designated for actual treatment using the apparatus.

12. The apparatus of claim 101 wherein said apparatus is for controlling the penetration depth of the active substance to be delivered by iontophoresis.

13. The apparatus of claim 12, wherein the substrate is a semi-solid layer.

14. The apparatus of claim 12, wherein the plurality of variables includes substrate pore size and pore density, amount and duration of energy applied to the electrodes and the physiochemical such as conductivity properties of the formulation.

15. The apparatus of claim 12, wherein the application of the active substance includes delivery of a greater amount of the active substance into the skin than is delivered through the skin, as determined analytically using an in-vitro skin penetration test system.

16. The apparatus of claim 15, wherein the in-vitro skin penetration test system is selected from ‘

Dual Chamber In-Vitro Test’

or ‘

Patch-sealed chamber test.’

17. The apparatus of claim 15, wherein the exposure time in the in-vitro skin penetration test system is equivalent to the time designated for actual treatment using the apparatus.

18. The apparatus of claim 101, wherein said apparatus is for controlling the penetration depth of an iontophoretic application of said formulation.

19. The apparatus of claim 18, wherein the plurality of variables includes substrate pore size and pore density, amount and duration of energy applied to the first and the second electrodes and the physiochemical such as conductivity) properties of the formulation.

20. The apparatus of claim 18, wherein the application of the active substance includes delivery of a greater amount of the active substance into the skin than is delivered through the skin, as determined analytically using an in-vitro skin penetration test system.

21. The apparatus of claim 20, wherein the in-vitro skin penetration test system is selected from ‘

Dual Chamber In-Vitro Test’

or ‘

Patch-sealed chamber test.’

22. The apparatus of claim 20, wherein the exposure time in the in-vitro skin penetration test system is equivalent to the time designated for actual treatment using the apparatus.

66. The apparatus of claim 1, wherein said patch, consists essentially of an electrochemical cell having at least two electrodes positioned on one side of the dermal patch, said electrodes being for forming electrical contact with a skin portion of a subject, said patch being designed and configured for delivering an electric current through a conductive fluid being deposited on at least one of said at least two electrodes and/or topically applied onto the skin portion of the subject and through the skin.

67. The apparatus of claim 66, wherein said at least two electrodes are integrally formed with said electrochemical cell.

68. The apparatus of claim 66, wherein said electrochemical cell and said at least two electrodes are the sole constituents of said patch.

69. The apparatus of claim 66, further comprising an attachment mechanism for attaching to the skin portion of the subject.

70. The apparatus of claim 66, further comprising a circuitry for controlling said electric current.

71. The apparatus of claim 66, wherein said electrochemical cell is a flexible thin layer electrochemical cell.

72. The apparatus of claim 66, wherein said electrochemical cell is a flexible thin layer open liquid state electrochemical cell which comprises a first layer of insoluble negative pole, a second layer of insoluble positive pole and a third layer of aqueous electrolyte, said third layer being disposed between said first and second layers and including:

(a) a deliquescent material for keeping the open cell wet at all times;

(b) an electroactive soluble material for obtaining required ionic conductivity; and

(c) a water-soluble polymer for obtaining a required viscosity for adhering said first and said second layers to said third layer.

73. The apparatus of claim 66, packaged and identified for an application selected from the group consisting of a wound healing application, a tissue repair application, a tissue regeneration application, a transdermal delivery application, an intradermal delivery application and an electrical stimulation application.

101. The apparatus of claim 1, further comprising a substrate, wherein said substrate is for storing the formulation and for contacting a first region of skin and said first electrode.

102. The apparatus of claim 4, wherein said delivery of a greater amount of the active substance into the skin than is delivered through the skin is determined analytically using an in-vitro skin penetration test system

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23. A method for enhancing application and containment of a substantial amount of a formulation containing an active substance in a layer of skin comprising:

contacting the formulation with an outer layer region of the skin;

applying an electromotive force onto the outer layer region to cause a penetration of the active substance into the skin layer; and

minimizing the penetration of the active substance through the skin layer by adjusting at least one variable from a group of variables;

wherein the group of variables includes a substrate pore size and pore density, the active substance'"'"'s physiochemical properties and the voltage and current density supplied by the power source.

24. The method of claim 23, wherein the active substance is included in a hydrogel adapted to attached to one of the electrodes.

25. The method of claim 24, wherein the hydrogel is adapted to adhere to the skin surface, conduct electrical current and to release the active substance into the skin.

26. The method of claim 23, wherein the application of the active substance includes delivery of a greater amount of the active substance into the skin than is delivered through the skin, as determined analytically using an in-vitro skin penetration test system.

27. The method of claim 26, wherein the in-vitro skin penetration test system is selected from ‘

Dual Chamber In-Vitro Test’

or ‘

Patch-sealed chamber test.’

28. The method of claim 26, wherein the exposure time in the in-vitro skin penetration test system is equivalent to the time designated for actual treatment using the apparatus.

29. A method for treating dermatological disorders comprising:

contacting a formulation having an active substance with an outer layer region of the skin;

applying an electromotive force onto the outer layer region to cause a penetration of the active substance into the skin layer; and

minimizing the penetration of the active substance through the skin layer by adjusting at least one variable from a group of predetermined variables;

wherein the predetermined group of variables includes a substrate pore size and pore density, the active substance'"'"'s physiochemical properties and the voltage and current density supplied by the power source.

30. The method of claim 29, wherein the dermatological disorders include dermatitis, bacterial infection, fungal skin infection, viral skin infection, disorders of the hair follicles, scaling diseases, scars, benign tumors and malignant tumors.

31. The method of claim 29, wherein the active substance contains one or more of anti-inflammatory agents, antibiotics, antifungal agents, antiviral agents, keratolytic agents, sulfur and sulfur-containing agents, steroidal and non-steroidal agents, anti-proliferative agents, melanin synthesis inhibitors and enhancers, and anticancer agents.

32. The method of claim 29, wherein the application of the active substance includes delivery of a greater amount of the active substance into the skin than is delivered through the skin, as determined analytically using an in-vitro skin penetration test system.

33. The method of claim 32, wherein the in-vitro skin penetration test system is selected from ‘

Dual Chamber In-Vitro Test’

or ‘

Patch-sealed chamber test.’

34. The method of claim 32, wherein the exposure time in the in-vitro skin penetration test system is equivalent to the time designated for actual treatment using the apparatus.

35. The method of claim 29, wherein the formulation, comprises a stratum corneum hydrating agent.

36. The method of claim 32, wherein the hydrating agent is selected from the group comprising urea, propylene glycol, glycerol, an alpha hydroxy acid and a beta hydroxy acid.

37. The method of claim 32, wherein the concentration of the hydrating agent is between 2% and 25% by weight of the final formulation.

38. The method of claim 29, wherein the formulation includes a hydrogel containing the active substance.

39. The method of claim 38, wherein the hydrogel is adapted to adhere to a skin surface, conduct electrical current and to release the active substance into the skin.

40. The method of claim 38, wherein the hydrogel is a semi-solid layer.

41. A composition for iontophoretic delivery of an active ingredient into the skin, while minimizing the penetration of the active substance through the skin, comprising a stratum corneum hydrating agent.

42. The composition of claim 41, wherein the hydrating agent is selected from the group comprising urea, propylene glycol, glycerol, an alpha hydroxy acid and a beta hydroxy acid.

43. The composition of claim 41, wherein the concentration of the hydrating agent is between 2% and 25% by weight of the final formulation.

44. A method for selecting the parameters of a device for delivering an active substance to the skin for the treatment of a cosmetic or medical disorder, comprising:

assembling a receiving compartment, filled with a receiving vehicle capable of dissolving an active substance, covered by a sheet of excised human or swine skin and sealed from above by an actual patch pole in intimate contact with a formulation containing an active substance, wherein the patch pole is linked to an externally controlled and monitored power supply, which is linked to the receiving compartment via an electrical cord;

applying a set electrical current for a set period of time, which is an acceptable time of treatment for the intended cosmetic or medical disorder; and

analyzing the amount of active substance in the skin and in the receiving compartment after the set period of time.

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74. A method of transdermal or intradermal delivery of at least one substance, the method comprising:

(a) topically applying a conductive fluid containing said at least one substance onto a skin portion of a subject and/or depositing said conductive fluid containing said at least one substance onto at least one electrode of a dermal patch which comprises an electrochemical cell having at least two electrodes positioned on one side of said dermal patch;

(b) positioning said dermal patch such that said electrodes are in electrical contact with the skin portion of a subject; and

(c) delivering an electric current through said conductive fluid and the skin of the subject so as to transdermally or intradermally deliver said at least one substance.

75. The method of claim 74, further comprising attaching the dermal patch to the skin of the subject via an attachment mechanism.

76. The method of claim 74, wherein said conductive fluid is an aqueous based fluid.

77. The method of claim 74, wherein said conductive fluid is a hydrogel.

78. The method of claim 74, wherein said conductive fluid is selected from the group consisting of a gel, a cream, a paste, a lotion, a suspension, an emulsion and a solution.

79. The method of claim 74, wherein said conductive fluid is for deposition on at least one of said at least two electrodes.

80. The method of claim 74, wherein said conductive fluid is for topical application to the skin portion of the subject.

81. The method of claim 74, wherein said at least one substance is a charged substance.

82. The method of claim 74, wherein said at least one substance is an uncharged substance.

83. The method of claim 74, wherein said electric current is for causing iontophoresis, electrophoresis, electroporation or any combination thereof.

84. The method of claim 74, wherein said at least one substance is selected from the group consisting of a pharmaceutical, a cosmetic and a cosmeceutical active agent.

85. The method of claim 84, wherein said pharmaceutical is selected from the group consisting of a therapeutic and an anesthetic.

86. The method of claim 74, wherein said conductive fluid is retained within a retainer.

87. The method of claim 86, wherein said retainer is a separator for deposition on at least one of said at least two electrodes such that, upon contact by said separator with the skin portion, said electric current causes said transdermal or intradermal delivery of said at least one substance.

88. The method of claim 86, wherein said retainer is a separator for deposition upon the skin portion such that, upon contact by said separator with at least one of said at least two electrodes, said electric current causes said transdermal or intradermal delivery of said at least one substance.

89. The method of claim 87, wherein said separator is contained in a removable cover.

90. The method of claim 74, wherein said retainer is selected from the group consisting of a vessel, a tube, a jar, a container, a dispenser and an ampoule.

91. The method of claim 74, wherein said at least two electrodes are integrally formed with said electrochemical cell.

92. The method of claim 74, wherein said electrochemical cell and said at least two electrodes are the sole constituents of said patch.

93. The method of claim 74, wherein the dermal patch further comprises an attachment mechanism for attaching to the skin portion of the subject.

94. The method of claim 74, wherein at least one electrode of said at least two electrodes is for mobilizing said at least one substance.

95. The method of claim 74, wherein said electric current is for causing iontophoresis, electrophoresis, electroporation or any combination thereof.

96. The method of claim 74, wherein the dermal patch further comprises a circuitry for controlling said electric current.

97. The method of claim 74, wherein said electrochemical cell is a flexible thin layer electrochemical cell.

98. The method of claim 74, wherein said electrochemical cell is a flexible thin layer open liquid state electrochemical cell which comprises a first layer of insoluble negative pole, a second layer of insoluble positive pole and a third layer of aqueous electrolyte, said third layer being disposed between said first and second layers and including:

(a) a deliquescent material for keeping the open cell wet at all times;

(b) an electroactive soluble material for obtaining required ionic conductivity; and

(c) a water-soluble polymer for obtaining a required viscosity for adhering said first and said second layers to said third layer.

99. A device for providing electrical stimulation to the skin of a subject, comprising:

(a) a dermal patch,

(b) an electrochemical cell; and

(c) at least two electrodes electrically connected to the electrochemical cell.

100. The device of claim 99 wherein:

said electrochemical cell is a flexible thin layer open liquid state electrochemical cell which comprises a first layer of insoluble negative pole, a second layer of insoluble positive pole and a third layer of aqueous electrolyte, said third layer being disposed between said first and including;

(a) a deliquescent material for keeping the open cell wet at all times;

(b) an electroactive soluble material for obtaining required ionic conductivity; and

(c) a water-soluble polymer for obtaining a required viscosity for adhering said first and said second layers to said third layer.