# US 12,397,141 B2 · Thermally regulated transdermal drug delivery system > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,397,141 B2 - Document ID: US12397141B2 - Status: Granted - Kind: B2 - Application number: 17/293,570 - Filed: 2019-11-15 - Published: 2022-01-06 - Granted: 2025-08-26 - Earliest claimed: 2018-11-16 - Assignees: Morningside Venture Investments Limited - Applicants: Morningside Venture Investments Limited - Inventors: Patrick H. Ruane; Jackie Joe Hancock; Anubhav Arora - Web page: https://patentgrep.com/patent/US12397141B2 ## CPC - A61F 13/00063: {comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic (drug delivery dressings A61K9/70; chemical aspect of the additives A61L15/00)} - 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) - A61K 9/0009: {involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis} - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - A61K 9/0097: {Medicinal compositions released by microdevices, e.g. microelectromechanical systems [MEMS], microdevices comprising chips or microdevices on silicon} - A61K 9/7038: {Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer} - A61K 31/465: Nicotine; Derivatives thereof - 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} - A61M 2205/055: with electrophoresis - A61M 2205/3606: cooled - A61M 2205/368: by electromagnetic radiation, e.g. IR waves - A61M 2205/8206: battery-operated - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Described herein are drug and other active agent transdermal delivery systems and devices to deliver active agents to skin or mucosa of a subject, and methods of delivering such active agents. In particular, systems, methods, and devices are described that control the concentration and timing of active agent delivery. Such systems or devices may include a transdermal membrane and a temperature control element for heating and/or cooling a portion of the transdermal delivery system to provide pulsatile active agent delivery through the transdermal membrane. ## Claims ### Claim 1 A transdermal delivery system comprising: a transdermal membrane; a first active agent contained within a reservoir separate from and fluidically connected to the transdermal membrane, the transdermal membrane configured to control, in response to temperature, a flow of the first active agent from the reservoir to skin of a subject; and a temperature control element configured to cyclically heat to a first temperature and/or cool a portion of the transdermal delivery system so as to provide pulsatile delivery of the first active agent through the transdermal membrane, wherein the temperature control element is further configured to cyclically heat to a second temperature, different from the first temperature, the portion of the transdermal delivery system so as to provide pulsatile delivery of a second active agent through the transdermal membrane. ### Claim 2 (depends on 1) The transdermal delivery system of claim 1, wherein the temperature control element comprises an electromagnetic energy source. ### Claim 3 (depends on 1) The transdermal delivery system of claim 1, wherein the temperature control element comprises a resistive element. ### Claim 4 (depends on 1) The transdermal delivery system of claim 1, wherein the temperature control element comprises an inductive coil or an electromagnet. ### Claim 5 (depends on 1) The transdermal delivery system of claim 1, wherein the temperature control element comprises a coolant or heat sink. ### Claim 6 (depends on 1) The transdermal delivery system of claim 1, wherein the portion of the transdermal membrane comprises a polymer configured to be heated or cooled to thereby change active agent flow. ### Claim 7 (depends on 1) The transdermal delivery system of claim 1, wherein the portion of the transdermal membrane comprises a glass transition polymer configured to be heated or cooled to thereby change active agent flow. ### Claim 8 (depends on 1) The transdermal delivery system of claim 1, wherein the portion of the transdermal membrane comprises a magnetic nanoparticle configured to be heated or cooled to thereby change active agent flow. ### Claim 9 (depends on 1) The transdermal delivery system of claim 1, wherein the first active agent comprises nicotine or a nicotine agonist. ### Claim 10 (depends on 1) The transdermal delivery system of claim 1, wherein the first active agent comprises a Parkinson's disease treatment. ### Claim 11 (depends on 1) The transdermal delivery system of claim 1, wherein the first active agent comprises at least one of benztropine, carbidopa, dopamine, a dopamine analog, a dopamine antagonist, a dopamine agonist, entacapone, levodopa (L-dopa), pramipexole, rasagiline, ropinirole, rotigotine, safinamide, selegiline, both carbidopa and levodopa, trihexyphenidyl and tolcapone. ### Claim 12 (depends on 1) The transdermal delivery system of claim 1, further comprising an adhesive in the transdermal membrane configured to adhere the transdermal membrane to the subject. ### Claim 13 (depends on 1) The transdermal delivery system of claim 1, further comprising an adhesive in the transdermal membrane, wherein the adhesive contains the first active agent. ### Claim 14 (depends on 1) The transdermal delivery system of claim 1, further comprising a temperature sensor configured to measure the temperature of at least one of the temperature control element, the portion of the transdermal delivery system, or the transdermal membrane. ### Claim 15 (depends on 1) The transdermal delivery system of claim 1, further comprising a power source configured to provide power to the temperature control element. ### Claim 16 (depends on 1) The transdermal delivery system of claim 1, further comprising a circuit board. ### Claim 17 (depends on 1) The transdermal delivery system of claim 1, further comprising a microcontroller configured to control delivery of a stimulus from the temperature control element. ### Claim 18 (depends on 1) The transdermal delivery system of claim 1, further comprising a communication element configured to receive or transmit data. ### Claim 19 (depends on 18) The transdermal delivery system of claim 18, wherein the communication element comprises Bluetooth or WiFi. ### Claim 20 A method for transdermally delivering an active agent, comprising: cyclically heating to a first temperature and cooling a portion of a transdermal delivery system for a first amount of time; and after the first amount of time, cyclically heating to a second temperature and cooling the portion of the transdermal delivery system for a second amount of time, wherein the cyclic heating or cooling steps provide a pulsatile delivery of a first active agent from a reservoir based on the first temperature and a pulsatile deliver of a second active agent based on the second temperature, through a transdermal membrane of the transdermal delivery system to skin of a patient, wherein the transdermal membrane controls a flow of the first active agent and the second active agent in response to temperature. ### Claim 21 (depends on 20) The method of claim 20, wherein the cyclically heating or cooling steps comprise delivering heat to the portion of the transdermal delivery system. ### Claim 22 (depends on 20) The method of claim 20, wherein the cyclically heating or cooling steps comprise removing heat from the portion of the transdermal delivery system. ### Claim 23 (depends on 20) The method of claim 20, wherein at least one of the cyclically heating or cooling steps comprises delivering electromagnetic radiation to the portion of the transdermal delivery system. ### Claim 24 (depends on 20) The method of claim 20, further comprising repeating the cyclic heating or cooling steps at least once. ### Claim 25 (depends on 20) The method of claim 20, further comprising repeating the cyclic heating or cooling steps at least twice. ### Claim 26 (depends on 20) The method of claim 20, wherein the portion of the transdermal delivery system is increased in temperature by at least 4° C. during the cyclic heating and cooling steps. ### Claim 27 (depends on 20) The method of claim 20, further comprising actively heating skin of the subject adjacent the transdermal membrane by at least 3° C. during the cyclic heating or cooling steps. ### Claim 28 (depends on 20) The method of claim 20, wherein at least one of the actively heating or cooling steps is performed while the subject is sleeping. ### Claim 29 A transdermal delivery system comprising: a transdermal membrane; a first active agent contained within a reservoir separate from and fluidically connected to the transdermal membrane, the transdermal membrane configured to control, in response to temperature, a flow of the active agent from the reservoir to skin of a subject; and a temperature control element configured to provide a first stimulus to a portion of the transdermal delivery system so as to provide pulsatile delivery of the first active agent through the transdermal membrane to the skin of the subject and provide a second stimulus to the portion of the transdermal delivery system so as to provide pulsatile delivery of a second active agent through the transdermal membrane, wherein the first stimulus is a first temperature and the second stimulus is a second temperature that is different than the first temperature. ### Claim 30 (depends on 29) The transdermal delivery system of claim 29, further comprising a reactive material configured to prevent the active agent from flowing across the transdermal membrane until the stimulus is applied. ### Claim 31 (depends on 30) The transdermal delivery system of claim 30, wherein the reactive material comprises an epoxy, a polyethylene, a polymethacrylate, a polypropylene, a polypropylene glycol, a polyvinylacetate, a polystyrene, a polytetrafluoroethylene, a poly(bisphenol A carbonate), a poly(ethylene terephthalate), a polylactic acid (PLA), a polyglycolic acid (PGA), or a polyurethane. ### Claim 32 (depends on 30) The transdermal delivery system of claim 30, wherein the reactive material comprises a polymer, a hydrogel, a solvent, gold covered nanoparticles, or magnetic nanoparticles.