Reduction of skin irritation and resistance during electrotransport
First Claim
1. In a method of delivering an agent by electrotransport through a body surface, said method including placing an anodic reservoir and a cathodic reservoir of an electrotransport agent delivery device in ion-transmitting relation with said body surface, at least one of the reservoirs containing the agent to be delivered, applying an electrical potential across the anodic and cathodic reservoirs in order to deliver the agent through the body surface by electrotransport;
- the improvement comprising during said electrotransport agent delivery, performing a step selected from the group consisting of;
(a) maintaining, during electrotransport agent delivery the anodic reservoir at a pH above 4 and maintaining, during electrotransport agent delivery, the cathodic reservoir at a pH below 4; and
(b) maintaining, during electrotransport agent delivery, the cathodic reservoir at a pH below 4.
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Accused Products
Abstract
An electrotransport delivery device utilizing reservoir buffering at a select pH ranges in order to reduce skin irritation and skin resistance is provided. Cathodic reservoirs are buffered to a pH of less than about 4, preferably to a pH in the range of about 2 to 4, while anodic reservoirs are buffered to a pH above about 4, preferably to a pH in the range of about 4 to 10. Another electrotransport delivery device utilizes a potassium sensor to monitor potassium efflux from the skin. Potassium efflux above a certain predetermined level has been found to be a precursor to skin irritation/erythema. Operation of the device is modified (eg, terminated) when the predetermined potassium efflux level is sensed.
97 Citations
17 Claims
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1. In a method of delivering an agent by electrotransport through a body surface, said method including placing an anodic reservoir and a cathodic reservoir of an electrotransport agent delivery device in ion-transmitting relation with said body surface, at least one of the reservoirs containing the agent to be delivered, applying an electrical potential across the anodic and cathodic reservoirs in order to deliver the agent through the body surface by electrotransport;
- the improvement comprising during said electrotransport agent delivery, performing a step selected from the group consisting of;
(a) maintaining, during electrotransport agent delivery the anodic reservoir at a pH above 4 and maintaining, during electrotransport agent delivery, the cathodic reservoir at a pH below 4; and (b) maintaining, during electrotransport agent delivery, the cathodic reservoir at a pH below 4. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
- the improvement comprising during said electrotransport agent delivery, performing a step selected from the group consisting of;
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16. In a method of delivering an agent by electrotransport through a body surface, said method including placing an anodic reservoir and a cathodic reservoir of an electrotransport agent delivery device in ion-transmitting relation with said body surface, at least one of the reservoirs containing the agent to be delivered, applying an electrical potential across the anodic and cathodic reservoirs in order to deliver the agent through the body surface by electrotransport;
- the improvement comprising during said electrotransport agent delivery, performing a step selected from the group consisting of;
(a) maintaining, during electrotransport agent delivery, the anodic reservoir at a pH above 4, wherein said anionic reservoir is buffered with an anionic buffer selected from the group consisting of histidine, lysine, arginine, aspartic acid, glutamic acid, cysteine, tyrosine, and combinations thereof; and (b) maintaining, during electrotransport agent delivery, the cathodic reservoir t a pH below 4.
- the improvement comprising during said electrotransport agent delivery, performing a step selected from the group consisting of;
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17. In a method of delivering an agent by electrotransport through a body surface, said method including placing an anodic reservoir and a cathodic reservoir of an electrotransport agent delivery device in ion-transmitting relation with said body surface, at least one of the reservoirs containing the agent to be delivered, applying an electrical potential across the anodic and cathodic reservoirs in order to deliver the agent through the body surface by electrotransport;
- the improvement comprising during said electrotransport agent delivery, performing a step selected from the group consisting of;
(a) maintaining, during electrotransport agent delivery, the anodic reservoir at a pH above 4, wherein said anodic reservoir is buffered with a buffer selected from the group consisting of; (i) aspartic acid, glutamic acid, succinic acid, phosphoric acid, acetic acid, lactic acid, boric acid, carbonic acid, monobasic sodium phosphate, benzoic acid, tartaric acid, maleic acid, fumaric acid, sulfuric acid, formic acid, malic acid, malonic acid, glutaric acid, and adipic acid; (ii) tromethamine, triethanolamine, imidazole, ammonia, ethanolamine, diethanolamine, histidine, lysine, and arginine; (iii) calcium chloride dihydrate, triethanolamine hydrochloride, magnesium chloride heptahydrate, diethanolamine hydrochloride, ammonium chloride, ethanolamine hydrochloride, potassium chloride, and sodium chloride; (iv) 2-(N-morpholino)-ethane sulfonic acid, 1,4-piperazine-bis-(ethanesulfonic acid), N-2-acetamido iminodiacetic acid, N-2(2-acetamido)-2-aminoethane sulfonic acid, N,N-bis(2-hydroxyethyl)-2-aminoethane sulfonic acid, 2-(N-morpholino) -propane sulfonic acid, N-tris hydroxymethyl) methyl-2-aminoethane sulfonic acid, N-2-hydroxyethyl piperazine-N'"'"'-2-ethane sulfonic acid, 4-(2-hydroxyethyl) -1-piperazine propane sulfonic acid, N-tris(hydroxymethyl) methyl-2-aminopropane sulfonic acid, 2-cyclohexylamino-1-ethane sulfonic acid, 3-cyclohexylamino-1-propanesulfonic; and (v) polyacrylic acid, polymethacrylic acid, poly(styrene maleic anhydride), methacrylic/divinyl benzene copolymers, poly(2-acrylamido-2-methylpropane sulfonate), copolymers of acrylic acid and long chain acrylate esters, and poly(methylvinyl ether-maleic acid); and (b) maintaining, during electrotransport agent delivery, the cathodic reservoir at a pH below 4.
- the improvement comprising during said electrotransport agent delivery, performing a step selected from the group consisting of;
Specification