CA2112366A1 - Method and apparatus for treating tissue - Google Patents
Method and apparatus for treating tissueInfo
- Publication number
- CA2112366A1 CA2112366A1 CA002112366A CA2112366A CA2112366A1 CA 2112366 A1 CA2112366 A1 CA 2112366A1 CA 002112366 A CA002112366 A CA 002112366A CA 2112366 A CA2112366 A CA 2112366A CA 2112366 A1 CA2112366 A1 CA 2112366A1
- Authority
- CA
- Canada
- Prior art keywords
- electrode device
- electrode
- tissue
- treated
- area
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0408—Use-related aspects
- A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
- A61N1/0432—Anode and cathode
- A61N1/044—Shape of the electrode
Abstract
A method of delivering topical drugs to the tissue includes the step of applying the drug to be delivered to one of an area of tissue to be treated and an electrode device (10). The electrode device, which is formed to generate a multiplicity of simultaneous and directionally distinct electrical fields, is then placed in contact with the area of tissue to be treated. Voltage is delivered to the electrode device to generate simultaneous and directionally distinct electric fields at the tissue surface.
Description
WO 93/OOg59 PCI`/US92/05587 . ~.
2 t l 23 6 6 METHOD AND APPARATUS FOR TREATING
TISSUE
s Field of the Invention This invention relates to a novel method and apparatus for treating tissue, including the application of an electric field to tissue surfaces as well as the delivery of topical drugs to an area of tissue to be treated using such electric field. More specifically, the invention relates to methods of delivering topical drugs, including proteins ~and nucleic acids, to skin by electrically stimulating the skin. Further, the invention relates to the transdérmal delivery of electrical - stimuIation across the skin boundary to treat the underlying . 25 tissue. Such treatment can include the delivery of a drug or - other compound to such tissue.
, ~ , ~ , .
Background Iontophoresis is a well known technique for - 30 delivering drugs through the skin which involves applying an electric potential gradient at the skin surface to enhance the permeability of the skin to the drug molecules. Research has been conducted on iontophoretic transdermal delivery of S~JBSTITU~E SHEET
WO g3/00959 PCI /US92/05587 ~ 1 12 3 ~ ~ 2 peptide and protein drugs (Chien, Yie W., et al., ~1989) ~. of Phann. ~ ~, 376-383); nonpeptide drugs (Sanderson, et al., (1989) J. of Pharm. ~, 361-364); and polypeptide drugs (Srinivasan, V., et al., (1989) ~ of Pharm. Sci. Z~, ~70-375).
s Iontophoresis has proven effective for transdermal delivery of local anesthesia, metallic and nonmetallic ions, vasodilators, dermatological medications, and steroids (Behl, et al. (1989) J. of Pharm. Sci. ~ 355-360). One of the earliest uses of iontophoresis involved introducing a sweat-inducing drug through the skin to diagnose cystic fibrosis (Chien, Yie W., et al. (1989) J. of Pharm. Sci. ~, 353-354). Other biomedical applications of ; iontophoresis include treatment for hyperhidrosis, edema ~' formation, calcium deposits, and hay fever (Behl, et al., (1989) J. of Pharm. Sci. 78, 355-360).
An iontophoretic drug delivery system generally includes a power source, control circuitry, and two electrode pads. One of the electrode pads contains a solution of an ionic drug and the other electrode pad contains an electrolyte. To effect delivery of the drug,~the electrode pads are placed on the skin, and an electric current is supplied to the pads to induce an electric field at the skin surface. The power supply is connected to the electlode pads so that the charge of the pole connected to the drug-containing electrode is the same as the charge of the ionic drug.~ The application of an electric potential at the drug-containing electrode will drive the drug ions through the skin and into the body (Sanderson, John E. et al. (1987) J. of Pharm. Sci. ~, 215-218; Phipps, J. B., et al.
(1989) J. of Pharm. ~i,~., 365-369).
,,~
One such iontophoretic drug delivery system, marketed by Iomed, Inc. under the trademark TransQl, includes a dispersive electrode and a drug delivery electrode.
The drug delivery electrode is mounted to a plastic holding ~ SU~STiTUrE SHEE~
WO g3/00959 2 1 1 2 3 ~ ~ PCI`/US92/05587 tray which includes an absorbent pad for receiving the drug.
Once the pad is fully hydrated with the drug, the drug delivery electrode and absorbent pad are separated from the holding tray and placed on the skin at the treatment site. The dispersive electrode is placed on the skin spaced from the drug delivery electrode, and leads are attached to the pair of electrodes to generate an electric potential gradient at the trea~ment site. This drug delivery system is primarily used to deliver a water soluble medication, such as a local anesthetic o and/or corticosteroid, through a patient's skin. A disadvantage of this system is ~e excessive length of time required for treatment.
Rogaine (Minoxidil, 2% topical solution) is a topically applied drug, marketed by the Upjohn Company, s which has proven effective in treating .nale pattern baldness involving ~e top, or vertex, of the head. Although Rogaine has successfillly stimulated hair growth on the top of ~e head, no clinically significant effect has been seen in patients ~,vith predominantly frontal hair loss.
Accordingly, it is therefore a general object of the invention to provide methods of treating the surface of tissue with an electric field.
It is a~ specific object of the invention to provide ; - - rnethods of applying a topical d~ug to a tissue which increases ` ~ 25~ the efficiency and effectiveness of the drug.
, It is a further specific object of the invention to provide a method of applying Rogaine to the frontal lobes of a -~ user's head which stirnula~es detectable hair growth.
It is anod er object of the invention to provide an - 30 electrode device for use with the subject method which is sterile, disposable, noninvasive, pain free, easy to manufacture, and inexpensive to mass produce.
SUBSlTIIII~ SHEET
WO 93/00959 PCI`/US92/OS587 ,~.~
.
211.~6 Disclosure of the Invention A preferred method of delivering topical drugs to the skin which is intended to accomplish at least some of the foregoing objects includes the step of applying the drug to be delivered to one of an area of skin to be treated and an electrode device. In a preferred embodiment, the drug is applied to the electrode device. The electrode device, whic;h is formed to generate a multiplicity of simultaneous and directionally distinct electrical fields, is then placed in contact with the area of skin to be treated. Finally, voltage is delivered to the electrode device to generate simultaneous and directionally distinct electric fields at the sldn surface.
Such methods~ and apparatus may be readily applied to similar treatment of other tissue surfaces. Further, such methods and apparatus may be readily adapted to apply ~ ~ ~unique electric f1elds to the~ surface of ~tiswe and to tissue !~ ~ ullderlying~ such tissue surfaces to enhance circulation or the d~elivery of drugs to suc~h dssue.
,;~ , - ~ , .
Brief ~Description of the ~Drawings Other objects~and~advantagcs of the present irlventi~on~will ;become~apparent~from the~following detailed descriptio n o f a~ pref ed embodiment thereof taken in . 25 conjunction with the accompanying drawings, wherein:
nauRE 1 is a~top~plan view of an electrode - device for use with the subject method of delivering topical drugstothe skin; ~ ~ ~
~ ~ FIGURE 2 is an enlarged top view of a section of -~ 30 the electrode device of Flgure l; and ~
,-:
~ SUBSTI~UIE SHEET
WO 93/OOgS9 PCI`/US92/05587 h ;1 ~ 2 ~ S ~
~:IGURES 3a-c are photographs of enhanced hair growth using the methods and apparatus of the invention.
Best Mode of Carrying Out the Invention s Before describing the subject methods of applying novel electric fields and the delivery of drugs to a tissue surface or underlying tissue, it may be helpful to describe the electrode device for use with the subject method. Referring to the drawings, wherein lilce numerals indicate like partsi and o initially to FlGURE 1, there will be seen an electrode device 10 including a substantially planar support member 12 composed of a substantially non-conductive material. This device in general is made of a flexible planar support member to accommodate the contours of the tissue surface to be : 15 ~treated. Suitable non-conductive materials for forming support member 12 include mica, ~polyester, and polystyfene. Support member ~12 has ~ ~a main portion~ 14~ preferably circular in shape, and a~ tab~portion 16 ~extending from the~perimeter of ~ortion 14. ~ Tab~pôItion~ 16 facilitates connection of lead ~lines~to electrode d~evice lO. ~
A f~st~ electrode pattern 18a and a second electrodé~-patt~em~ 18b ~are disposed on main portion l4 of elec~rode~devicë 10.~ st electrode pattern 18a;and second ;el~ctfodè pattérn 1~8b~each~lude a~set of substandally - ~ : 25 ~ pafalld~electrodes~20a~ and-~20b, respectively, which extend ~, across main~ portion 14 in an alternating arrangement.
;Electrodes~20a~;and-20b~-are uniformly spaced across main portion 14;~to ensu~e~sn~even distribution of current density - beneath elect~ode dèvice lO,~tbe eby reducing the likelihood of skinbums. ~
A~ pair of eIectrode leads 22a and 22b extend along opposite sides of tab portion 16 and halfway around the ' ' ~, ' .
.
~ SU~ST~UTE SHEE~
r~
WO 93/OOgS9 PCI`/US92/05587 ~, A ,~
i.,l ~/J~ 6 perimeter of main portion 14. Electrodes 20a are electrically coupled together by electrode lead 22a, and electrodes 20b are electrically interconnected by electrode lead 22b. Each set of electrodes 20a and 2ûb are electrically connected to one s another so that a voltage applied to the corresponding electrode leads 22a and 22b is uniformly distributed across each of the electrodes.
The alternating arrangement of ~lrst and second electrode patterns 18a and 18b, respectively, generates multiple directionally distinct electrical fields when opposite charges are applied to electrode leads 22a and 22b. Turning to FIGURE 2, the arrows represent electric field lines generated by connecting lead lines of opposite polarity to electrode leads æa and 22b.
s Al~ough a preferred embodimen~ of support member 12 is circular in shape, support member 12 may be fabricated in different shapes according to the area of tissue to be`treated and according to the specific medical application.
Electrode patterns may be formed by screen printing a conductive ink on support member 12. A technique for printing a conductive ink on a flexible substrate is disclosed by M. Martel in "The Basics of; Area Source IR", SITe Magazine. pgs. 60-64. Suitable conductive inks for - folminc the electrode pattems of the subject invention include 2~ E-1400 ink marketed by Ercon ~corporated and Electrodag PTF inks marketed by ~cheson Colloids Company.
Alternatively, the electrode patterns may be formed by selectively depositing a metallic material, such as aluminum, on main portion 14. Or, the elec¢rode patterns may be formed by using a mas~ing technique to deposit copper vapor or other metallic vapor such as aluminum, gold, platinum, and nickel, on main portion 14.
SU~STI~UrE SHEET
WO93/OOg59 f.,.. ~.~' 23~ PCl/US92/05587 . ~
The methods used to produce such vapor deposited electrode devices and selectively etched electrode devices are well known. Metal deposition may be carried out according to the methods disclosed by P. Gise and R.
Blanchard in "Modern Semiconductor Pabrication Technology", ~hapter 8 (Prentice-Hall, England Cliffs, New Jersey, 1986), and A.B. Glaser and G.E. Subak-Sharpe in "Integrated Circuit Engineering", Chapter S (Addison-Wesley, Reading, Massachusetts, 1977) and selective etching of o laminated material may be carried out according to the methods disclosed by C.F. Coombs, Jr., ed., in "Printed Circuit Handbook", Chapters 1 and 8 (McGraw-Hill, New York, New York, 1976).
The electrode material preferably ranges in s thickness from approximately .001 inches to 1 inch. Each electrode has a width of approximately lO,um to 2mm, preferably between O.lmm and Imm. The spacing between the electrodes ranges from approximately lO~lm to 2mm, preferably O.lmm to Imm.
Since these electrodes are positioned close together, a user may apply a relatively low voltage across first and second electrode leads 22a and 22b to generate an appropriate voltage gladient or sufficient electrical current.
mos~ applications, 10 to 100 volts DC are applied across 2s ele de leads 22a and 2Zb; however, the applied voltage may ~nge from approxinutely I to 500 volts DC. It is preferable to deliver a pulsed voltage, as opposed to a continuous voltage, to electrode device 10 to ~prevent the build-up of charge on the ~; ski~
The subject method for delivering a topical drug to tissue will now be ~described. According to the subject method, a topical drug is applied to one of an area of tissue to be treated and electrode device 10. Tissue includes but is not - ~UBS~ITIJTE SHEET
WO 93/OOg59 PCI'/US92/05587 2 1 1 ~ 8 limited to skin, tendons, muscles, nerves, internal organs and tissues of the oral cavity. ~ a preferred embodiment, the drug is applied to a localized area of skin to ensure even distribution of the drug across the skin surface. If the`drug is s applied directly to electrode device 10, the drug should be spread evenly across the surface of device 10 on which electrode patterns 18a and 18b are disposed, or the conductive surface of device 10- Once the drug has been applied, the - conductive surface of device 10 is placed in contact with the o area of skin to be treated. A voltage is then applied acr~ss electrode leads 22a and 22b to generate simultaneous and directionaUy distinct electric fields between electrodes 20a and 20b. The electric fields electrically stimulate the area of skin being treated. Although the exact mechanism is unknown, it is believed that 3pplication of electric fields to the skin surface enhances the ~ermeability of the skin to the topical drug, ~ereby increasing the absorption of the drug through the skin.
The increased absorption contributes to an increase in the efficiency and effectiveness of the drug delivery.
: . .
The subject method of the invention may be used in combination with the topical hair growth drug Rogaine, commercia11y marketed by The Upjohn Company. Previously, Rogaine has only been successful in promoting hair growth on - dle vertex of the head. However, when used in combination2s ~ with elec~ode device 10, Rogaine has been shown to stimulate hair growd~ on the front of-the scalp. According to the subject method, a user applies a full dose of Rogaine, specifically ImL, to the front of the sc`alp per the directions found in the literature accompanying a Rogaine prescription. After the full dose has been applied to the user's scalp with the supplied rub-ON applicator, the user places the conductive surface of electrode device 10 in contact with the area of the scalp to be treated. The user then tums on the power supply to electrode device 10 which is preferably set to deliver approximately fifty to one hundred 100 volt DC pulses of 1 ampere of SUBST~TUT~ SHErT
WO 93/00959 PCI`/US92/05587 2 1 1,~3~1~
g current over a period of 15 to 30 seconds, each pulse lasting approximately 1 to 10 msec. As the pulses are being applied to electrode device 10, the user may move electrode device 10 over the area of skin being treated. The user may selectively apply pressure to electrode device 10 to adjust the contact of electrode device 10 with the skin. During treatment, the user may feel a sensation of mild tingling. After approximately four months of treatment, hair growth becomes apparent. This was repeated twice daily over 60 days.
o The results of applying Rogaine to the frontal lobe of the scalp and treating the scalp with the electrode device as described above over a 60 day period are shown in FIGURES 3a-c. PIGURE 3a shows the condition of the scalp on day 0 prior to the start of the experiment. FIGURES 3b and 3c show the same scalp after 20 and 60 days, respectively.
TISSUE
s Field of the Invention This invention relates to a novel method and apparatus for treating tissue, including the application of an electric field to tissue surfaces as well as the delivery of topical drugs to an area of tissue to be treated using such electric field. More specifically, the invention relates to methods of delivering topical drugs, including proteins ~and nucleic acids, to skin by electrically stimulating the skin. Further, the invention relates to the transdérmal delivery of electrical - stimuIation across the skin boundary to treat the underlying . 25 tissue. Such treatment can include the delivery of a drug or - other compound to such tissue.
, ~ , ~ , .
Background Iontophoresis is a well known technique for - 30 delivering drugs through the skin which involves applying an electric potential gradient at the skin surface to enhance the permeability of the skin to the drug molecules. Research has been conducted on iontophoretic transdermal delivery of S~JBSTITU~E SHEET
WO g3/00959 PCI /US92/05587 ~ 1 12 3 ~ ~ 2 peptide and protein drugs (Chien, Yie W., et al., ~1989) ~. of Phann. ~ ~, 376-383); nonpeptide drugs (Sanderson, et al., (1989) J. of Pharm. ~, 361-364); and polypeptide drugs (Srinivasan, V., et al., (1989) ~ of Pharm. Sci. Z~, ~70-375).
s Iontophoresis has proven effective for transdermal delivery of local anesthesia, metallic and nonmetallic ions, vasodilators, dermatological medications, and steroids (Behl, et al. (1989) J. of Pharm. Sci. ~ 355-360). One of the earliest uses of iontophoresis involved introducing a sweat-inducing drug through the skin to diagnose cystic fibrosis (Chien, Yie W., et al. (1989) J. of Pharm. Sci. ~, 353-354). Other biomedical applications of ; iontophoresis include treatment for hyperhidrosis, edema ~' formation, calcium deposits, and hay fever (Behl, et al., (1989) J. of Pharm. Sci. 78, 355-360).
An iontophoretic drug delivery system generally includes a power source, control circuitry, and two electrode pads. One of the electrode pads contains a solution of an ionic drug and the other electrode pad contains an electrolyte. To effect delivery of the drug,~the electrode pads are placed on the skin, and an electric current is supplied to the pads to induce an electric field at the skin surface. The power supply is connected to the electlode pads so that the charge of the pole connected to the drug-containing electrode is the same as the charge of the ionic drug.~ The application of an electric potential at the drug-containing electrode will drive the drug ions through the skin and into the body (Sanderson, John E. et al. (1987) J. of Pharm. Sci. ~, 215-218; Phipps, J. B., et al.
(1989) J. of Pharm. ~i,~., 365-369).
,,~
One such iontophoretic drug delivery system, marketed by Iomed, Inc. under the trademark TransQl, includes a dispersive electrode and a drug delivery electrode.
The drug delivery electrode is mounted to a plastic holding ~ SU~STiTUrE SHEE~
WO g3/00959 2 1 1 2 3 ~ ~ PCI`/US92/05587 tray which includes an absorbent pad for receiving the drug.
Once the pad is fully hydrated with the drug, the drug delivery electrode and absorbent pad are separated from the holding tray and placed on the skin at the treatment site. The dispersive electrode is placed on the skin spaced from the drug delivery electrode, and leads are attached to the pair of electrodes to generate an electric potential gradient at the trea~ment site. This drug delivery system is primarily used to deliver a water soluble medication, such as a local anesthetic o and/or corticosteroid, through a patient's skin. A disadvantage of this system is ~e excessive length of time required for treatment.
Rogaine (Minoxidil, 2% topical solution) is a topically applied drug, marketed by the Upjohn Company, s which has proven effective in treating .nale pattern baldness involving ~e top, or vertex, of the head. Although Rogaine has successfillly stimulated hair growth on the top of ~e head, no clinically significant effect has been seen in patients ~,vith predominantly frontal hair loss.
Accordingly, it is therefore a general object of the invention to provide methods of treating the surface of tissue with an electric field.
It is a~ specific object of the invention to provide ; - - rnethods of applying a topical d~ug to a tissue which increases ` ~ 25~ the efficiency and effectiveness of the drug.
, It is a further specific object of the invention to provide a method of applying Rogaine to the frontal lobes of a -~ user's head which stirnula~es detectable hair growth.
It is anod er object of the invention to provide an - 30 electrode device for use with the subject method which is sterile, disposable, noninvasive, pain free, easy to manufacture, and inexpensive to mass produce.
SUBSlTIIII~ SHEET
WO 93/00959 PCI`/US92/OS587 ,~.~
.
211.~6 Disclosure of the Invention A preferred method of delivering topical drugs to the skin which is intended to accomplish at least some of the foregoing objects includes the step of applying the drug to be delivered to one of an area of skin to be treated and an electrode device. In a preferred embodiment, the drug is applied to the electrode device. The electrode device, whic;h is formed to generate a multiplicity of simultaneous and directionally distinct electrical fields, is then placed in contact with the area of skin to be treated. Finally, voltage is delivered to the electrode device to generate simultaneous and directionally distinct electric fields at the sldn surface.
Such methods~ and apparatus may be readily applied to similar treatment of other tissue surfaces. Further, such methods and apparatus may be readily adapted to apply ~ ~ ~unique electric f1elds to the~ surface of ~tiswe and to tissue !~ ~ ullderlying~ such tissue surfaces to enhance circulation or the d~elivery of drugs to suc~h dssue.
,;~ , - ~ , .
Brief ~Description of the ~Drawings Other objects~and~advantagcs of the present irlventi~on~will ;become~apparent~from the~following detailed descriptio n o f a~ pref ed embodiment thereof taken in . 25 conjunction with the accompanying drawings, wherein:
nauRE 1 is a~top~plan view of an electrode - device for use with the subject method of delivering topical drugstothe skin; ~ ~ ~
~ ~ FIGURE 2 is an enlarged top view of a section of -~ 30 the electrode device of Flgure l; and ~
,-:
~ SUBSTI~UIE SHEET
WO 93/OOgS9 PCI`/US92/05587 h ;1 ~ 2 ~ S ~
~:IGURES 3a-c are photographs of enhanced hair growth using the methods and apparatus of the invention.
Best Mode of Carrying Out the Invention s Before describing the subject methods of applying novel electric fields and the delivery of drugs to a tissue surface or underlying tissue, it may be helpful to describe the electrode device for use with the subject method. Referring to the drawings, wherein lilce numerals indicate like partsi and o initially to FlGURE 1, there will be seen an electrode device 10 including a substantially planar support member 12 composed of a substantially non-conductive material. This device in general is made of a flexible planar support member to accommodate the contours of the tissue surface to be : 15 ~treated. Suitable non-conductive materials for forming support member 12 include mica, ~polyester, and polystyfene. Support member ~12 has ~ ~a main portion~ 14~ preferably circular in shape, and a~ tab~portion 16 ~extending from the~perimeter of ~ortion 14. ~ Tab~pôItion~ 16 facilitates connection of lead ~lines~to electrode d~evice lO. ~
A f~st~ electrode pattern 18a and a second electrodé~-patt~em~ 18b ~are disposed on main portion l4 of elec~rode~devicë 10.~ st electrode pattern 18a;and second ;el~ctfodè pattérn 1~8b~each~lude a~set of substandally - ~ : 25 ~ pafalld~electrodes~20a~ and-~20b, respectively, which extend ~, across main~ portion 14 in an alternating arrangement.
;Electrodes~20a~;and-20b~-are uniformly spaced across main portion 14;~to ensu~e~sn~even distribution of current density - beneath elect~ode dèvice lO,~tbe eby reducing the likelihood of skinbums. ~
A~ pair of eIectrode leads 22a and 22b extend along opposite sides of tab portion 16 and halfway around the ' ' ~, ' .
.
~ SU~ST~UTE SHEE~
r~
WO 93/OOgS9 PCI`/US92/05587 ~, A ,~
i.,l ~/J~ 6 perimeter of main portion 14. Electrodes 20a are electrically coupled together by electrode lead 22a, and electrodes 20b are electrically interconnected by electrode lead 22b. Each set of electrodes 20a and 2ûb are electrically connected to one s another so that a voltage applied to the corresponding electrode leads 22a and 22b is uniformly distributed across each of the electrodes.
The alternating arrangement of ~lrst and second electrode patterns 18a and 18b, respectively, generates multiple directionally distinct electrical fields when opposite charges are applied to electrode leads 22a and 22b. Turning to FIGURE 2, the arrows represent electric field lines generated by connecting lead lines of opposite polarity to electrode leads æa and 22b.
s Al~ough a preferred embodimen~ of support member 12 is circular in shape, support member 12 may be fabricated in different shapes according to the area of tissue to be`treated and according to the specific medical application.
Electrode patterns may be formed by screen printing a conductive ink on support member 12. A technique for printing a conductive ink on a flexible substrate is disclosed by M. Martel in "The Basics of; Area Source IR", SITe Magazine. pgs. 60-64. Suitable conductive inks for - folminc the electrode pattems of the subject invention include 2~ E-1400 ink marketed by Ercon ~corporated and Electrodag PTF inks marketed by ~cheson Colloids Company.
Alternatively, the electrode patterns may be formed by selectively depositing a metallic material, such as aluminum, on main portion 14. Or, the elec¢rode patterns may be formed by using a mas~ing technique to deposit copper vapor or other metallic vapor such as aluminum, gold, platinum, and nickel, on main portion 14.
SU~STI~UrE SHEET
WO93/OOg59 f.,.. ~.~' 23~ PCl/US92/05587 . ~
The methods used to produce such vapor deposited electrode devices and selectively etched electrode devices are well known. Metal deposition may be carried out according to the methods disclosed by P. Gise and R.
Blanchard in "Modern Semiconductor Pabrication Technology", ~hapter 8 (Prentice-Hall, England Cliffs, New Jersey, 1986), and A.B. Glaser and G.E. Subak-Sharpe in "Integrated Circuit Engineering", Chapter S (Addison-Wesley, Reading, Massachusetts, 1977) and selective etching of o laminated material may be carried out according to the methods disclosed by C.F. Coombs, Jr., ed., in "Printed Circuit Handbook", Chapters 1 and 8 (McGraw-Hill, New York, New York, 1976).
The electrode material preferably ranges in s thickness from approximately .001 inches to 1 inch. Each electrode has a width of approximately lO,um to 2mm, preferably between O.lmm and Imm. The spacing between the electrodes ranges from approximately lO~lm to 2mm, preferably O.lmm to Imm.
Since these electrodes are positioned close together, a user may apply a relatively low voltage across first and second electrode leads 22a and 22b to generate an appropriate voltage gladient or sufficient electrical current.
mos~ applications, 10 to 100 volts DC are applied across 2s ele de leads 22a and 2Zb; however, the applied voltage may ~nge from approxinutely I to 500 volts DC. It is preferable to deliver a pulsed voltage, as opposed to a continuous voltage, to electrode device 10 to ~prevent the build-up of charge on the ~; ski~
The subject method for delivering a topical drug to tissue will now be ~described. According to the subject method, a topical drug is applied to one of an area of tissue to be treated and electrode device 10. Tissue includes but is not - ~UBS~ITIJTE SHEET
WO 93/OOg59 PCI'/US92/05587 2 1 1 ~ 8 limited to skin, tendons, muscles, nerves, internal organs and tissues of the oral cavity. ~ a preferred embodiment, the drug is applied to a localized area of skin to ensure even distribution of the drug across the skin surface. If the`drug is s applied directly to electrode device 10, the drug should be spread evenly across the surface of device 10 on which electrode patterns 18a and 18b are disposed, or the conductive surface of device 10- Once the drug has been applied, the - conductive surface of device 10 is placed in contact with the o area of skin to be treated. A voltage is then applied acr~ss electrode leads 22a and 22b to generate simultaneous and directionaUy distinct electric fields between electrodes 20a and 20b. The electric fields electrically stimulate the area of skin being treated. Although the exact mechanism is unknown, it is believed that 3pplication of electric fields to the skin surface enhances the ~ermeability of the skin to the topical drug, ~ereby increasing the absorption of the drug through the skin.
The increased absorption contributes to an increase in the efficiency and effectiveness of the drug delivery.
: . .
The subject method of the invention may be used in combination with the topical hair growth drug Rogaine, commercia11y marketed by The Upjohn Company. Previously, Rogaine has only been successful in promoting hair growth on - dle vertex of the head. However, when used in combination2s ~ with elec~ode device 10, Rogaine has been shown to stimulate hair growd~ on the front of-the scalp. According to the subject method, a user applies a full dose of Rogaine, specifically ImL, to the front of the sc`alp per the directions found in the literature accompanying a Rogaine prescription. After the full dose has been applied to the user's scalp with the supplied rub-ON applicator, the user places the conductive surface of electrode device 10 in contact with the area of the scalp to be treated. The user then tums on the power supply to electrode device 10 which is preferably set to deliver approximately fifty to one hundred 100 volt DC pulses of 1 ampere of SUBST~TUT~ SHErT
WO 93/00959 PCI`/US92/05587 2 1 1,~3~1~
g current over a period of 15 to 30 seconds, each pulse lasting approximately 1 to 10 msec. As the pulses are being applied to electrode device 10, the user may move electrode device 10 over the area of skin being treated. The user may selectively apply pressure to electrode device 10 to adjust the contact of electrode device 10 with the skin. During treatment, the user may feel a sensation of mild tingling. After approximately four months of treatment, hair growth becomes apparent. This was repeated twice daily over 60 days.
o The results of applying Rogaine to the frontal lobe of the scalp and treating the scalp with the electrode device as described above over a 60 day period are shown in FIGURES 3a-c. PIGURE 3a shows the condition of the scalp on day 0 prior to the start of the experiment. FIGURES 3b and 3c show the same scalp after 20 and 60 days, respectively.
3 The right side of the scalp (left side in the figures) is the area treated with Rogaine and the electrode device 10. The left side of the scalp (right side in the figures) is the control area, i.e., treated only with Rogaine. ~n FIGURE 3b, new hair grow~ is seen at 20 days. As is also apparent in FIGURE 3c, hair gro~h after just 60 days was substantial.
, , .~ ., The subject dectrode device 10 may also be used in combination with o~ier topical drugs to treat a variety of ~ ~ - skin maladies including: (i) Retin A ~retinoin, all, trans : :~ 25 Retinoic ~Acid3, commercially marketed by OrthoPharmaceuticals,~for treatment of brown spots, acne, and wrinkles, (ii) steroids to treat inflammation and psoriasis, (iii) topical pain relievers for treatment of aberrations of the skin - and underlying tissue, and (iv) S-fluorouracil to treat skin ~; 30 cancer and psoriasis.
addition to delivering drugs to a localized area - of skin and skin tissue, electrode device 10 may also be used without an accompanying topical drug. Electrical stimulation SUE~TlllJTE SHEET
WO 93/00959 PCI`/US92/05587 3 6 ~ , alone bas therapeudc and diagnostic value. Electrode device 10 may be used to electrically stimulate the skin of a user to, for example, increase blood flow, induce secretions, and. stimulate nerves.
s As an example, tests were performed where the electrode device 10 was applied to the inner forearm area of a human. The same protocol as previously described was used except no topical drug was applied to the skin or electrode device 10. The test produced a region of redness indicatmg o increased circulation to the area. The increased circulation is ' useful for enhancing the delivery of drugs to the localized skin , area which are administered IV or orally.
An advantage of using the apparatus and method of the invention lies in the fact that treatment can be effected without significant discomfort of tissue damage (even after twice daily treatment for almost six months). The only feeling sensed by the user is a mere tingling of the scalp which is believed to be evidence of subcutaneous nerve stimulation.
: .
Electr~de device 10 may also provide gene therapy to skin or other tissue by transfecting nucleic acid into the cells of the skin or tissue or cells underlying such surfaces for treatmg~ gene deficiencies or inducing-such deficiencies in laboratory ~animals. Nucleic acids which~ may be used for transfection include DNA capable of e~ssing an antisenæ
RNA transcript which is capable of down modulating translation of endogenous~RNA transcripts. Proteinaceous gene products may also be delivered to the skin cells by the subject method. ~Such proteins include Factor VIII, insulin, and adenosine deaminase.
- In describing the invention, reference has been ~; made to a preferred embodiment and illustrative advantages of the invention. lhose skilled in ~e art, however, and familiar with the instant disclosure f the subject invention, will SUBSTITUTE SHEET
WO 93/00959 2 1 1 .~ 3 ~i ~ PCI/US92/05587 ~.
recognize additions, deletions, modifications, substitutions, and other changes which will fall within the purview of the subject invention and claims.
. ,j , ~
.
, :
, SUBSTITUTE SHEET
, , .~ ., The subject dectrode device 10 may also be used in combination with o~ier topical drugs to treat a variety of ~ ~ - skin maladies including: (i) Retin A ~retinoin, all, trans : :~ 25 Retinoic ~Acid3, commercially marketed by OrthoPharmaceuticals,~for treatment of brown spots, acne, and wrinkles, (ii) steroids to treat inflammation and psoriasis, (iii) topical pain relievers for treatment of aberrations of the skin - and underlying tissue, and (iv) S-fluorouracil to treat skin ~; 30 cancer and psoriasis.
addition to delivering drugs to a localized area - of skin and skin tissue, electrode device 10 may also be used without an accompanying topical drug. Electrical stimulation SUE~TlllJTE SHEET
WO 93/00959 PCI`/US92/05587 3 6 ~ , alone bas therapeudc and diagnostic value. Electrode device 10 may be used to electrically stimulate the skin of a user to, for example, increase blood flow, induce secretions, and. stimulate nerves.
s As an example, tests were performed where the electrode device 10 was applied to the inner forearm area of a human. The same protocol as previously described was used except no topical drug was applied to the skin or electrode device 10. The test produced a region of redness indicatmg o increased circulation to the area. The increased circulation is ' useful for enhancing the delivery of drugs to the localized skin , area which are administered IV or orally.
An advantage of using the apparatus and method of the invention lies in the fact that treatment can be effected without significant discomfort of tissue damage (even after twice daily treatment for almost six months). The only feeling sensed by the user is a mere tingling of the scalp which is believed to be evidence of subcutaneous nerve stimulation.
: .
Electr~de device 10 may also provide gene therapy to skin or other tissue by transfecting nucleic acid into the cells of the skin or tissue or cells underlying such surfaces for treatmg~ gene deficiencies or inducing-such deficiencies in laboratory ~animals. Nucleic acids which~ may be used for transfection include DNA capable of e~ssing an antisenæ
RNA transcript which is capable of down modulating translation of endogenous~RNA transcripts. Proteinaceous gene products may also be delivered to the skin cells by the subject method. ~Such proteins include Factor VIII, insulin, and adenosine deaminase.
- In describing the invention, reference has been ~; made to a preferred embodiment and illustrative advantages of the invention. lhose skilled in ~e art, however, and familiar with the instant disclosure f the subject invention, will SUBSTITUTE SHEET
WO 93/00959 2 1 1 .~ 3 ~i ~ PCI/US92/05587 ~.
recognize additions, deletions, modifications, substitutions, and other changes which will fall within the purview of the subject invention and claims.
. ,j , ~
.
, :
, SUBSTITUTE SHEET
Claims (17)
1. A method for delivering topical drugs to tissue comprising the steps of:
applying the drug to be delivered to one of an area of tissue to be treated and an electrode device formed to generate a multiplicity of simultaneous and directionally distinct electric fields;
placing said electrode device in contact with the area of tissue to be treated; and delivering voltage to said electrode device to generate a multiplicity of directionally distinct electrical fields at the tissue surface to electrically stimulate the area of tissue being treated.
applying the drug to be delivered to one of an area of tissue to be treated and an electrode device formed to generate a multiplicity of simultaneous and directionally distinct electric fields;
placing said electrode device in contact with the area of tissue to be treated; and delivering voltage to said electrode device to generate a multiplicity of directionally distinct electrical fields at the tissue surface to electrically stimulate the area of tissue being treated.
2. A method as defined in claim 1 wherein:
said electrode device includes a flexible, nonconductive, substantially planar support member, and first electrode means and second electrode means each including at least two electrically connected, substantially parallel electrodes, said first electrode means and said second electrode means arranged on a planar surface of said electrode device so that the electrodes of said first electrode means alternate with the electrodes of said second electrode means and, upon connection to said power supply, said electrode device generates said multiplicity of directionally distinct electric fields between the electrodes of said first electrode means and the electrodes of said second electrode means.
said electrode device includes a flexible, nonconductive, substantially planar support member, and first electrode means and second electrode means each including at least two electrically connected, substantially parallel electrodes, said first electrode means and said second electrode means arranged on a planar surface of said electrode device so that the electrodes of said first electrode means alternate with the electrodes of said second electrode means and, upon connection to said power supply, said electrode device generates said multiplicity of directionally distinct electric fields between the electrodes of said first electrode means and the electrodes of said second electrode means.
3. A method as defined in claim 1 wherein:
said applying step is accomplished by coating the area of tissue being treated with the drug.
said applying step is accomplished by coating the area of tissue being treated with the drug.
4. A method as defined in claim 1 further comprising the step of:
after delivering said step, moving said electrode device over the area of tissue being treated.
after delivering said step, moving said electrode device over the area of tissue being treated.
5. A method as defined in claim 1 further comprising the step of:
after said delivering step, applying selective pressure to said electrode device to adjust contact of said electrode device with the area of tissue being treated.
after said delivering step, applying selective pressure to said electrode device to adjust contact of said electrode device with the area of tissue being treated.
6. A method as defined in claim 1 wherein:
said delivering step is accomplished by connecting a power supply to said electrode device to deliver a pulsed voltage to said electrode device.
said delivering step is accomplished by connecting a power supply to said electrode device to deliver a pulsed voltage to said electrode device.
7. A method as defined in claim 6 wherein:
said power supply delivers approximately 50 to 100 voltage pulses over approximately 15 to 30 seconds to said electrode device.
said power supply delivers approximately 50 to 100 voltage pulses over approximately 15 to 30 seconds to said electrode device.
8. A method as defined in claim 7 wherein:
said power supply is set to deliver voltage pulses of approximately 100 volts at about 1 ampere, each having a duration approximately 1 to 10 msec.
said power supply is set to deliver voltage pulses of approximately 100 volts at about 1 ampere, each having a duration approximately 1 to 10 msec.
9. A method as defined in claim 1 wherein:
said delivering step is accomplished by connecting a power supply to said electrode device to deliver a continuous voltage to said electrode device.
said delivering step is accomplished by connecting a power supply to said electrode device to deliver a continuous voltage to said electrode device.
10. A method as defined in claim 1 wherein:
said electrode device is formed in the shape of the area of tissue to be treated.
said electrode device is formed in the shape of the area of tissue to be treated.
11. A method as defined in claim 2 wherein:
said second electrode means are formed by conductive inks.
said second electrode means are formed by conductive inks.
12. A method of providing electrical stimulation to tissue comprising the steps of placing an electrode device in contact with the tissue, said electrode device formed to generate a multiplicity of directionally distinct electric fields, and delivering voltage to said electrode device to generate a multiplicity of simultaneous and directionally distinct electric fields at the tissue surface to electrically stimulate the issue.
13. A mud as recited in claim 12, wherein said tissue stimulated by said electrode device is skin.
14. A method of stimulating hair growth on the head of a user comprising the steps of:
applying a hair growth drug to an area of skin to be treated;
placing an electrode device in contact with the area of skin to be treated, said electrode device formed to generate a a multiplicity of simultaneous and directionally distinct electric fields; and delivering voltage; to said electrode device to generate a multiplicity of directionally distinct electric fields at the skin surface to electrically stimulate the area of skin being treated.
applying a hair growth drug to an area of skin to be treated;
placing an electrode device in contact with the area of skin to be treated, said electrode device formed to generate a a multiplicity of simultaneous and directionally distinct electric fields; and delivering voltage; to said electrode device to generate a multiplicity of directionally distinct electric fields at the skin surface to electrically stimulate the area of skin being treated.
15. A method as defined in claim 14 wherein:
said applying step is accomplished by spraying said hair growth drug on the frontal portion of a user's head.
said applying step is accomplished by spraying said hair growth drug on the frontal portion of a user's head.
16. A method as defined in claim 14 wherein:
said applying step is accomplished by rubbing said hair growth drug on the frontal portion of a user's head.
said applying step is accomplished by rubbing said hair growth drug on the frontal portion of a user's head.
17. An electrical stimulation apparatus comprising:
a substantially planar support member having a substantially non-conductive surface, in contact with a tissue surface;
first electrode means comprising at least two electically-connected substantially parallel electrodes disposed on said substantially non-conductive surface; and second electrode means comprising at least two electrically-connected substantially parallel electrodes also disposed on the same surface as said first electrode means such that the electrodes of said first and second electrode means are alternately positioned on said surface.
a substantially planar support member having a substantially non-conductive surface, in contact with a tissue surface;
first electrode means comprising at least two electically-connected substantially parallel electrodes disposed on said substantially non-conductive surface; and second electrode means comprising at least two electrically-connected substantially parallel electrodes also disposed on the same surface as said first electrode means such that the electrodes of said first and second electrode means are alternately positioned on said surface.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US72527991A | 1991-07-03 | 1991-07-03 | |
| US725,279 | 1991-07-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2112366A1 true CA2112366A1 (en) | 1993-01-21 |
Family
ID=24913891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002112366A Abandoned CA2112366A1 (en) | 1991-07-03 | 1992-07-02 | Method and apparatus for treating tissue |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0600914A4 (en) |
| JP (1) | JPH06508783A (en) |
| AU (1) | AU2336992A (en) |
| CA (1) | CA2112366A1 (en) |
| IL (1) | IL102406A0 (en) |
| WO (1) | WO1993000959A1 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7643874B2 (en) | 2001-10-24 | 2010-01-05 | Power Paper Ltd. | Dermal patch |
| JP2003210591A (en) * | 2002-01-24 | 2003-07-29 | Hisamitsu Pharmaceut Co Inc | Percutaneous transmucosal applying preparation for electroporation |
| US8734421B2 (en) | 2003-06-30 | 2014-05-27 | Johnson & Johnson Consumer Companies, Inc. | Methods of treating pores on the skin with electricity |
| US7480530B2 (en) | 2003-06-30 | 2009-01-20 | Johnson & Johnson Consumer Companies, Inc. | Device for treatment of barrier membranes |
| US7476222B2 (en) | 2003-06-30 | 2009-01-13 | Johnson & Johnson Consumer Companies, Inc. | Methods of reducing the appearance of pigmentation with galvanic generated electricity |
| WO2010088914A1 (en) * | 2009-02-05 | 2010-08-12 | Aalborg Universitet | A device for controlling subcutaneous blood flow |
| US20120089232A1 (en) | 2009-03-27 | 2012-04-12 | Jennifer Hagyoung Kang Choi | Medical devices with galvanic particulates |
| US11110272B2 (en) | 2011-12-08 | 2021-09-07 | Pilogics L.P. | Apparatus for stimulating hair growth and/or preventing hair loss |
| US9566431B2 (en) | 2014-04-07 | 2017-02-14 | Pilogics L.P. | Method of forming a large number of metal-ion-deposition islands on the scalp by a rapid series of brief electrode-contact events |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2322615A1 (en) * | 1975-09-02 | 1977-04-01 | Le Goaster Jacqueline | Product application process to skin - uses magnetic field to accelerate particle passage through successive layers of tissue |
| US4164226A (en) * | 1976-08-25 | 1979-08-14 | Robert Tapper | Iontophoretic burn-protection electrode structure |
| GB2132892B (en) * | 1983-01-10 | 1986-10-08 | Hayashibara Ken | Device for stimulating growth and regeneration of hair |
| US4736752A (en) * | 1986-11-28 | 1988-04-12 | Axelgaard Manufacturing Co., Ltd. | Transcutaneous medical electrode |
| DE3736072A1 (en) * | 1987-09-24 | 1989-04-13 | Soft Electrics & Cosmetics Ver | Method and device for enhancing human well-being and for the cosmetic treatment of the skin |
| IL86076A (en) * | 1988-04-14 | 1992-12-01 | Inventor S Funding Corp Ltd | Transdermal drug delivery device |
| EP0419473A1 (en) * | 1988-11-28 | 1991-04-03 | Innofinance Altalanos Innovacios Penzintetet | Iontophoresis apparatus |
-
1992
- 1992-07-02 AU AU23369/92A patent/AU2336992A/en not_active Abandoned
- 1992-07-02 WO PCT/US1992/005587 patent/WO1993000959A1/en not_active Application Discontinuation
- 1992-07-02 EP EP9292915713A patent/EP0600914A4/en not_active Withdrawn
- 1992-07-02 CA CA002112366A patent/CA2112366A1/en not_active Abandoned
- 1992-07-02 JP JP5502332A patent/JPH06508783A/en active Pending
- 1992-07-03 IL IL102406A patent/IL102406A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2336992A (en) | 1993-02-11 |
| EP0600914A1 (en) | 1994-06-15 |
| IL102406A0 (en) | 1993-01-14 |
| WO1993000959A1 (en) | 1993-01-21 |
| JPH06508783A (en) | 1994-10-06 |
| EP0600914A4 (en) | 1994-11-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |