JP2002543942A - Remote and field controlled delivery of pharmaceutical compounds using electromagnetic energy - Google Patents

Abstract

  (57) [Summary] The present invention provides methods and systems for remotely and in situ controlled pharmaceutical compound transport or biomolecule collection using electromagnetic energy. Incorporate a controlled electromagnetic energy drive system into patches and other transport devices. Also provided are drug delivery patches or biomolecule collection patches that are monitored by a computer with a global positioning system.

Description

DETAILED DESCRIPTION OF THE INVENTION

RELATED APPLICATIONS This patent application (not a provisional patent application) claims the benefit of US Provisional Patent Application No. 60 / 134,486, filed May 17, 1999, now abandoned.

[0002] The present invention relates generally to the fields of medical physics and drug transport. More particularly, the present invention relates to methods and devices for controlling the transport of drugs across skin and other tissue interfaces.

Description of the Related Art Drug transport is an important aspect of therapy. In many cases, accurate administration of a drug is important to the overall effect of its action, and thus patient compliance is an important factor in treatment. For that reason, doctors need to closely monitor drug transport.

[0004] Drug transport is particularly important in emergency settings. Patients often have to withstand prolonged hospital stay after surgery or other treatment to confirm that the drug is being administered properly. In such cases and in many other cases, the patient must remain in close contact with the physician during the treatment period. The above compliance issues and the cost of prolonged hospital stay have led to significant research and development of devices that can provide controlled, continuous and sustained drug release.

[0005] Skin has a very thin layer of dead cells called the stratum corneum, which acts as a water impermeable layer for material on one side of the layer. The stratum corneum is the layer that primarily provides the barrier function of the skin. If the stratum corneum is ablated or otherwise altered, substances within the body can more easily diffuse out of the skin surface, and substances outside the body can more easily diffuse into the skin. Alternatively, compounds with permeation enhancers, such as alcohols, or drug carriers, such as liposomes, have been used with some success in penetrating the stratum corneum. In any case, the barrier function of the skin poses a very important challenge for pharmaceutical manufacturers interested in topical administration of drugs or transdermal collection of body fluids.

[0006] The mucosa, the wet lining of many tubular structures and cavities (eg, the sinuses and oral cavity), is composed, in part, of the epithelial surface layer. The surface layer consists of a mono- or multi-layered sheet of cells with strong intercellular connections, the sheet having non-keratinized or keratinized epithelium. The basolateral side of the epithelium is a thin layer of collagen, proteoglycans and glycoproteins called the basement membrane, which serves to bind the epithelial layer to adjacent cells or matrix. The mucous membrane acts as a barrier to prevent significant absorption of topically applied substances as well as detachment of biomolecules and substances from the body. The extent to which the mucosa acts as a barrier to a substance, and the exact nature of the substance to which it is impermeable or permeable, depends on the anatomical location. For example, the bladder epithelium is 10,000 times less "leaky" than the intestinal epithelium.

[0007] Mucous membranes differ substantially from skin in many ways. For example, mucous membranes do not have a stratum corneum. Regardless of the difference, the permeation of the compound across the mucosa is limited and somewhat selective. The latest model of mucosal permeability is a model in which adjacent cells in the epithelium are tightly bound by occlusal joints that inhibit the smallest molecule from dispersing through the mucosa, but allow the outflow of mucoid proteins. The molecular structure of the epithelium consists of a series of proteins that bind to each other between cells, as well as focal protein structures such as, for example, desmosomes. Although the permeability properties of the mucosa are not completely understood, it is believed that the selective permeability of the mucosa depends on the keratinized or non-keratinized epithelial layer as well as the basement membrane. Although it has been shown that ablation or alteration of the stratum corneum of the skin leads to improved skin permeability,
There is no corresponding layer on the mucous membrane to be changed. Therefore, it is not clear that irradiation of electromagnetic energy causes a change in permeability of the mucosa.

[0008] Various methods have been used to enhance the transport of compounds across the skin and other membranes. Ionization therapy uses an electric current to increase the rate of penetration of charged molecules.
However, ionization therapy has been found to be dependent on the charge density of the molecule and to cause further burning. The use of ultrasound has also been tested, and the application of ultrasound energy to the skin results in a transient change in the skin, thereby increasing the permeability of the substance. The stratum corneum can be ablated using electromagnetic energy created by a laser to increase the permeability of the skin to pharmaceuticals (U.S. Pat. No. 4,775,36)
No. 1), and furthermore, impulse transients created by laser or mechanical means can be used to effect changes in the epithelial layer to improve the permeability of the compound (US Pat. No. 5,614,502). ).

[0009] There are many therapeutic and diagnostic methods that would benefit from administration or collection by the transmucosal or transepithelial route. For example, a local anesthetic such as lidocaine is supplied to an area before treatment. Such topical administration of lidocaine will not only be effective in delivering anesthetics, but will also minimize side effects and eliminate the need for a needle. Local administration of an anesthetic to the bladder wall can minimize the time a patient needs to keep the drug in the bladder during chemotherapy.

Electrosurgery is a method that can affect tissue coagulation and / or dissociation. In electrosurgery, a tissue is exposed to radio frequency (RF) current by an (active) electrode. In a bipolar system, current passes through tissue between two electrodes on the same surgical instrument, such as tweezers. In a monopolar system, a return pass (outer) electrode is provided to make intimate electrical contact with certain parts of the patient. Since it is important that the outer electrode provide the lowest electrical resistance conductive path for current flow, protection circuits are often used to monitor contact between the outer electrode and the patient, and the outer electrode-skin resistance The rise results in equipment shutdown. Factors associated with the electrosurgical system include the shape of the treatment electrode, the position of the electrode relative to the tissue surface (contact or non-contact), the frequency and modulation of the RF, the power of the RF and the time applied to the tissue surface,
The peak-to-peak voltage of the radio wave, as well as the type of tissue. In a typical electrosurgical system, radio frequencies from 300 kHz to 4 MHz are used because nerve and muscle excitation stops at frequencies above 100 kHz. For example, all else being the same, a smaller electrode size results in a higher current density in tissue adjacent to the electrode, and also results in a more invasive tissue effect compared to aggregation, such as, for example, dissociation. Similarly, where everything else is the same, the range of RF-tissue interaction is small when the electrode is held close to the tissue but not in contact (compared to when the electrode is in contact with the tissue). The effect on the tissue is more invasive. By changing the applied RF waveform from a continuous sinusoid to a packet of high peak voltage sinusoids (ie, about 6% duty cycle) separated by dead time, the tissue effect (all others are the same) is shifted from separation to aggregation. Can be changed. Keeping everything else the same and increasing the voltage of the waveform increases the invasiveness of the tissue effect. Of course, exposing tissue to radio waves for a longer period of time will result in greater tissue effects. Finally, different tissues respond differently to radio waves due to their different electrical and electrical properties that carry ions and different thermal properties.

The prior art lacks effective means of utilizing electromagnetic energy to control the rate of drug transport or biomolecule collection, such as incorporating a controlled electromagnetic energy drive system into patches and other delivery devices. The present invention fulfills such a long standing need and desire in the art.

SUMMARY OF THE INVENTION The present invention is directed to analog and digital communication lines, including the Internet,
Provide a microprocessor that can control and communicate. Specifically, the present invention provides
A microprocessor controlled transdermal patch using electromagnetic energy to enhance uptake of the formulation in contact with the membrane or skin is described. The device can also be used to enhance the diffusion of substances and biomolecules from tissue. The electromagnetic energy specific to the invention described herein includes microwave (MW) and radio wave (RF)
).

[0013] The application of the present invention is not limited to transport across the oral mucosa or skin. For example, it can be applied to the vagina, uterus, intestinal tract, buccal, tongue, pharyngeal cavity, anus, and bladder wall, as well as other anatomical tissues such as blood vessels, lymph vessels and urethra. Importantly, the present invention is used to transport many drug-containing compounds across the skin and across the intact skin, using the present invention to compromised or intact stratum corneum and its stratum corneum. The underlying tissue layer can be broken through. Furthermore, the method can be used to control systems that drive drugs across non-biological membranes and films.

In one embodiment of the invention, a method for controlling the transport of a pharmaceutical compound in a subject, comprising: irradiating the subject with electromagnetic energy; and further administering the pharmaceutical compound to the subject. Give: Provides a method that includes each step, such that the compound is contained in a patch. Preferably, the electromagnetic energy is selected from the group consisting of radio waves, microwaves, and light. The patch may be implanted in the subject, or may be locally positioned in relation to the subject, and may be on-site or remotely controlled, for example, by an external controller such as a microprocessor.

In another embodiment of the present invention, a system for controlling the rate of drug transport or biomolecule collection in a subject, comprising: means for producing electromagnetic energy; means for providing electromagnetic energy to the subject. And means for administering a drug to the subject or removing a biomolecule from the subject, wherein the drug is contained in a patch that is on-site or remotely controlled by an external controller. I will provide a. Preferably, the electromagnetic energy is selected from the group consisting of radio waves, microwaves, and light, and the means for creating electromagnetic energy includes a laser and an ultrasonic transducer. Preferably, the controller is a microprocessor powered by a dry cell, solar cell, electrochemical generator, thermal energy generator, or piezoelectric generator. The patch may be implanted in the subject, or may be locally positioned relative to the subject, and is further selected from the group consisting of bandaging materials, gels, viscous materials, and adhesive materials. It can be made from a substance.

[0016] In a preferred embodiment, the patch includes one or more reservoirs separated by a rupturable membrane. In the case of a multi-reservoir-containing patch, the lyophilized crystalline portion of the labile pharmaceutical compound is stored in one reservoir, while the liquid portion of the compound is stored in another reservoir. Examples of such compounds include prostaglandin E
1 is mentioned.

The above system may further include an electrode, which contacts both the patch and the controller to transfer current or electromagnetic radiant energy. The system may further include a computer monitor connected to the Internet, and the signal is sent through the Internet to the patch via the computer monitor.

In yet another embodiment of the present invention, there is provided a patch for drug delivery or biomolecule collection, the patch being monitored by a global positioning system on a computer.

[0019] Other aspects, features and advantages of the present invention will become apparent from the following description of the presently preferred embodiments of the invention, provided for purposes of disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS The above described features, advantages and objects of the present invention, as well as other features, points and objects that will become apparent, are set forth in the accompanying drawings so that they can be achieved and understood in detail. The present invention, briefly summarized above, will now be described in further detail by reference to specific embodiments of the invention that have been described above. These drawings form part of the present specification.
However, the attached drawings illustrate preferred embodiments of the present invention and therefore are not meant to limit the scope of the invention.

DETAILED DESCRIPTION OF THE INVENTION The present invention provides methods / means for remotely or in situ controlled delivery of pharmaceutical compounds using electromagnetic energy. The electromagnetic devices described herein, such as a laser system, can be used to affect drug transport and can be operated on-site or remotely by a microprocessor built into the device, which microprocessor can It is programmed to send and receive data over the network. The controlled electromagnetic energy drive system can be incorporated into patches and other transport devices that can be mounted or implanted on the skin.

The presently disclosed devices include a microprocessor or other electronic control element that is interrogated remotely or on site using an integrated or remote transmitter.
The transmitter itself can communicate over a telecommunications network. Devices used in paging systems are incorporated into transdermal patches to receive signals or codes sent by an operator over a telecommunications network. Control is provided by code systems, such as bar codes and magnetic codes, and is communicated by devices that create and read such codes. Also, the code is communicated through the Internet, either directly in the case of a visible code or by using a dedicated communication device to receive and process the code.

In one embodiment of the invention, a method for controlling the transport of a pharmaceutical compound in a subject, comprising: irradiating the subject with electromagnetic energy; and further providing the subject with the pharmaceutical compound: A method is provided that includes each step, wherein the compound is included in a patch. Preferably, the electromagnetic energy is selected from the group consisting of radio waves, microwaves, and light. More preferably, the patch may be implanted in the subject, or may be locally positioned relative to the subject, and may be on-site or remotely controlled, for example, by an external controller such as a microprocessor. Can be.

In a preferred embodiment, the patch can be made from a material selected from the group consisting of a dressing material, a gel, a viscous material, and an adhesive material.

In another preferred embodiment, the pharmaceutical compound is selected from the group consisting of an anesthetic, an anti-tumor agent, a photodynamic therapeutic, an anti-infective, and an anti-inflammatory. More preferably, the anesthetic is lidocaine.

In another embodiment of the present invention, a system for controlling the rate of drug transport or biomolecule collection in a subject, comprising: means for producing electromagnetic energy; delivering electromagnetic energy to the subject. Means for administering a drug to a subject or removing a biomolecule from a subject, wherein the system comprises a system wherein the drug is included in a patch that is on-site or remotely controlled by an external controller. provide. Preferably, the electromagnetic energy is selected from the group consisting of radio waves, microwaves, and light, and the means for creating the electromagnetic energy includes a laser and an ultrasonic transducer. More preferably, the controller is a microprocessor powered by a dry cell, solar cell, electrochemical generator, thermal energy generator, or piezoelectric generator. More preferably, the patch is implanted in the subject or is locally located in relation to the subject, and further comprises a material selected from the group consisting of a bandage material, a gel, a viscous material, and an adhesive material. In a preferred embodiment made from a patch, the patch comprises one or more reservoirs separated by a rupturable membrane. In the case of a multi-reservoir-containing patch, the lyophilized crystalline portion of the labile pharmaceutical compound is stored in one reservoir, while the liquid portion of the compound is stored in another reservoir. Examples of such compounds include prostaglandin E
1 is mentioned.

The above system may further include an electrode, which contacts both the patch and the controller to transmit current or electromagnetic radiant energy. The system may further include a computer monitor connected to the Internet, and the signal is sent to the patch via the Internet, via the computer monitor.

In yet another embodiment of the present invention, there is provided a patch for drug delivery or biomolecule collection, the patch being monitored by a global positioning system on a computer.

The following examples are given for the purpose of illustrating various embodiments of the present invention,
Neither is meant to limit the invention.

EXAMPLE 1 Compressive Waves for Carrying Compounds Through the Skin or Membrane Crossing the tissue interface, or at the membrane junction or between cells or between cell junctions as found through cell membranes To drive into the medium, compression waves created by the interaction of electromagnetic waves with tissue or non-biological material can be used. The interaction of radio- or macro-wave irradiation with tissue or another absorber and various formulations results in a propagating compression wave (in the form of low-pressure sound waves propagating at the speed of sound or high-pressure shock waves propagating at supersonic speeds). Resulting from rapid volume changes in the medium due to heating or due to the generation of a plasma). The waves may be the result of the generation of waves in non-living targets in close acoustic contact with the biological medium. The electromagnetic energy, delivered in discrete short-term pulses and producing a continuous pulse, propagates the compression wave, which physically moves the molecule between cell junctions or across membranes. By creating an overpressure, such as osmotic pressure or atmospheric pressure, a "pumping" effect occurs. Separation occurs because of the different tissue or membrane resistance compared to the mobile phase, the body fluid. The degree of pumping will be related to the drive RF waveform, duty cycle and power.

If energy is stored directly in the tissue, pumping will sometimes be inefficient due to its large surface area. To compensate for that inefficiency, a target substance that selectively absorbs energy at those radio frequencies can be placed adjacent to the tissue to effectively deliver energy. The target can effectively act as an antenna and can optionally include a metal or metal-containing compound.

Example 2 Compression Wave to Change the Barrier Function of the Skin or Membrane A compression wave can be used to change the skin or membrane itself, thereby reducing its barrier function. The change in barrier function is transient; the integrity of the barrier function is self-healing shortly after the impact of radiofrequency energy on the tissue ceases. The degree to which the barrier function is reduced depends on the wavelength and intensity of the radio wave irradiation. The drug to be given to the tissue is preferably placed during the irradiation.

Example 3 A force resulting from coherent interaction with dipole capture light is also referred to as a dipole force.
The laser field polarizes the atoms, which are subject to forces in the gradient of the electromagnetic field.
The strong electric field of a laser beam can be used to induce a dipole moment in a process called optical capture. As long as the frequency of the laser field is lower than the natural resonance of the trapped particles (eg, below the atomic transition of an atom, or below the absorption limit of a polystyrene sphere), the dipole moment is in phase with the driving electric field.
Since the energy of the dipole p induced in the laser field E is given by W = -pE, the particles are moved to the high-load focus of the laser beam by
Lower energy states can be achieved. There have been many reports of optical capture used to manipulate particles or cells. Such capture is used to move very small particles under a microscope for manipulation. Optical tweezers are also described, where the focal point of a single beam optical capture is moved using a mirror or lens.

In this study, dipoles are formed using radio or microwave energy rather than laser energy. A capture is formed at the interface between the molecule in the formulation and the tissue or membrane interface. The capture is moved in the desired direction of movement in vector.
In the case of drug delivery, the desired direction is the direction into the tissue. Thus, the focus of capture is moved along a vector that penetrates the tissue of interest, while the drug-containing formulation is applied to the tissue surface. The focus of a single beam or multiple beam capture is gradually moved into the tissue, the movement occurring periodically to ensure maximum pumping effect.

Example 4 Formation of Micropores in Skin or Membrane Small micropores are created in skin or membrane by applying electromagnetic energy using a needle-like probe. For example, a patch-like device having thousands of very small needle-like probes that conduct electromagnetic energy can supply energy to form micropores. The probes can be made from silicon with a metal conductive material.

EXAMPLE 5 Excision or Change of Membrane and Tissue Altering the epithelial layer of a tissue to "leak" the epithelial layer for substances such as drugs
In such a manner, radio frequency or microwave energy is directly applied to the tissue surface or a target adjacent to the tissue. In the case of skin, the stratum corneum is ablated by the use of electromagnetic energy to generate heat. Alternatively, shearing force can be created by targeting that energy to an absorber adjacent to the skin, which carries the energy to create a compression wave that changes or ablates the stratum corneum. In particular, radio waves that provide the desired rapid thermal effect on the stratum corneum result in an ablation event, but with minimal aggregation. Excision of the stratum corneum in such a manner will increase the permeability of the compound across the damaged tissue interface. For example, administration of 4% lidocaine to a portion of the skin from which the stratum corneum has been excised in the manner described above will provide a rapid anesthetic effect (several minutes until onset of anesthetic effect).

Alternatively, the electromagnetic energy can be optimized by adjusting the pulse time, dwell time between pulses, and maximum power to provide for rapid and intermittent excitation of the molecule in the tissue of interest. As a result, there is no eventual aggregation effect due to heating, but the molecules are temporarily altered to give a transient change in the membrane structure that results in "leakage" for substances such as drugs. Furthermore, those transients are maintained during the energy cycle, thus continuously providing energy with the appropriate pulse mode characteristics such that it creates a means to maintain increased membrane permeability over time. Hit it. The method allows the substance to be transported continuously over a desired period of time.

The combination of techniques for influencing the Example 6 molecular transport or collection: First El pressing pressure on permeable membrane, in order to improve transparency, to reorganize the film or intramembranous structure or a separate By applying electromagnetic energy, such as light, microwaves, or radio waves, to damage the membrane in a manner, a "leaky" membrane or ablation site is created in the skin. Following that step, an electromagnetic energy induced pressure is applied to transport molecules across the tissue interface and between cell junctions at a faster rate than can be achieved by either method alone. Laser energy can be supplied continuously or in discrete pulses to prevent micropore closure. If desired, a laser having a different wavelength than the wavelength used to create the micropores can be used side by side to deliver molecules through the micropores. Alternatively, a single laser may be adjusted so that the pulse width and energy change and alternate over time, with the next pulse creating alternating pores for carrying molecules.

Alternatively, intact skin is treated so as to impair the stratum corneum to reduce overall resistance to molecules and increase permeability. Following that step, an electromagnetic energy-induced pressure is applied to transport molecules across the tissue interface and between cell junctions at a faster rate than is achieved by either method alone.

The laser energy is directed through an optical fiber or guided through a series of optics such that a compression wave is generated to contact or create a gradient across the membrane surface. As needed, to create a pressure gradient such that the compression wave travels through the liquid or semi-solid medium, thereby "pushing" the compound into and across the membrane through the medium. The compression waves may be used.

For example, to supply laser energy for the purpose of drug transport across the buccal membrane, uterine membrane, mesentery, urethral membrane, vaginal membrane, bladder membrane, eyeball membrane, etc. Can be used. The pharmaceutical compound can be transported into the cell space beyond the membrane as described above, or into a chamber surrounded by the membrane. Also, by applying the appropriate light pressure, the damaged or intact stratum corneum can be broken.

[0042] As the electromagnetic energy absorption is maximized compared to Example 7 Formulation surrounding medium, to select a particular formulation. Furthermore, by adding an energy absorbing group (or selecting a group that minimizes absorption) to maximize the effect of electromagnetic energy on a particular formulation as compared to the surrounding medium or tissue, Many drugs or diagnostic compounds can be modified. Thus, a new class of compounds is defined as having unique permeability and migration properties during or after treatment with the electromagnetic energy described herein. Energy is provided in a characteristic manner, such as to give the molecule the driving force to move it relative to the medium in which it is contained, or to excite the molecule to make the desired change to the molecule. By adding absorbing groups or structures, the molecule has different properties. For example, rapid heating by radio or microwave of a molecule that selectively absorbs energy relative to its environment can result in the breakage of a heat-sensitive bond or the activation of a particular activity. To achieve the desired effect, the compounds are designed to include both bioactive groups and molecules that maximize the absorption or reflectance of energy.
In these embodiments, the molecule absorbs photons causing a transition between the ground state and the excited singlet state, and then immediately transfers energy to ground state oxygen to excite oxygen to the toxic excited singlet state. An analogy is drawn to such photodynamic therapy.

Similarly, pharmaceutically active compounds can be modified by the addition of groups that readily form dipoles when exposed to appropriate electromagnetic energy, such as, for example, radio waves or microwaves. The addition of such groups will increase the likelihood of using optical capture methods for transporting such types of compounds described herein. Further, any compound capable of interacting with electromagnetic energy to be propelled in a medium can be used. Thus, the present study is directed to a means by which molecules can be propelled in a medium at a differential rate compared to the medium and other molecules in the medium, and a means by which molecules can be separated from each other based on the optical properties of the molecules. Is specified.

The present application is not limited to transporting drugs. Other separations of molecules can be achieved by the methods described herein, such as, for example, separating protein species in a polyacrylamide gel or separating oligonucleotides on a microarray device. Embodiments also include the use of a magnetic field alone to propel molecules through a medium based on intrinsic magnetic properties or through the addition of magnetic groups or metals. Such methods can also be enhanced by working synergistically in combination with methods for altering membranes and tissues.

Although the problem is thermal destruction or electron destruction of molecules, this problem can be solved by selecting an appropriate carrier. The carrier chosen acts as a "sink" of energy, while stable functional groups are selected. By providing these "suctions" to the functional groups, energy is selectively absorbed into the suctions, thereby limiting exposure to the functional groups. Alternatively, it is possible to develop a molecule in which a functional group is bonded to a skeletal molecule that is easily cleaved when exposed to the electromagnetic energy described therein. In particular, radio waves will cause excessive vibration of the group as the group absorbs energy. Using a linker that is susceptible to cleavage when the atom is so vibrated will result in the release of a functional group of interest that can be a pharmaceutically active agent.

Example 8 Transdermal Patch A patch , such as a transdermal drug delivery patch, is controlled by remote or on-site operation via a microprocessor. Such patches are designed and used with electromagnetic energy driven transport systems.

The patches used herein include a dressing containing a gel or adhesive containing the formulation to be transported. The dressing material is in contact with the electrodes, which themselves are in contact with the controller (see FIG. 1). The controller regulates the flow of electromagnetic energy in contact with the electrodes. The electrodes also deliver energy into the formulation and into the tissue of interest. Outside of the bandage, the patch can be a gel, a viscous material, or other patch material that covers the treatment site.

A patch can contain one or more reservoirs. In the case of multiple reservoirs, the rupturable membrane separates the different chambers, thereby preventing the compounds from mixing until the membrane ruptures. For unstable compounds such as prostaglandin E1 (eg, Caverject, UpJohn), the lyophilized crystals are stored in one reservoir and the liquid component to be mixed with the drug is stored in another reservoir. be able to. The two reservoirs are separated by a membrane that can be ruptured by grinding or other physical means, thereby allowing the components to mix freely and be effective for dosing. The multiple reservoir concept is extended to include a mixture of chemicals that generate an electric current for the purpose of ionization therapy or electroporation.

Healing of the resection site will eventually reduce the amount of drug that permeates over time. Certain substances may be included in the formulation or patch and administered to the permeation / resection site, thereby slowing the healing process or reducing the rate of scab formation, thereby closing the permeable site. It has the effect of limiting the speed and extending the permeability of the irradiated site.

Embodiment 9 The communication system controller may include a constant current source driven by a portable battery, a solar generator, a thermal energy generator, a piezoelectric generator, a radio wave generator, a macro wave generator, or the like. Absent. The electrodes of the patch with a laser, multiple lasers, or fiber optics that conduct and transmit light at the desired wavelength, pulse width, pulse energy, pulse number, and pulse repetition rate to ablate or alter tissue immediately below the patch Can be replaced. Alternatively, a continuous wave laser can be used to effect a change in the tissue that has the effect of imparting permeability.
Lasers and other electromagnetic energy generators and ultrasonic transducers can be used in the controller-electrode combination that produces the desired effect. Also essential in the design of these patches is the ability to transport the drug at the same time as the energy, or at any time before or after the administration of the energy.

A telecommunications network transmits data between an operator and a remotely located controller (on a patch). The device is a telemetry device for transmitting data and issuing instructions between the device and an external patient communication control device located near the patient or at a remote location within the device's range of communication. Includes transceiver. The control device preferably comprises a communication line with a telemedicine support network via a telecommunications network, and furthermore a satellite positioning receiver for global positioning for receiving positioning data identifying the global position of the control device. May be included.

[0052] The device may also include a patient activation line to allow patient-driven personal communication with the medical support network. To selectively communicate patient-driven personal communications and global location data to the medical support network, to receive telemetry data from the data and to convey commands from the medical support network, and to receive from the medical support network A system controller in the controller controls the data and digital communications to receive and initiate reprogramming of the device operating modes and parameters with respect to the instructions. The communication link between the medical support network and the patient's communication controller may include a global satellite network, a hardwired telephone network, a cellular telephone network, or other personal communication system.

The purpose of the device is to provide the patient with mobility. The patient is allowed to walk while his condition is monitored and / or treated by the device. The programming device is controlled by a physician or pharmacist, as well as codes or data transmitted over a telecommunications network to the location of the device. It can be done remotely or on site. Currently, telemetry systems used to communicate with medical devices are located within close range of the device. In addition, transdermal patch systems are currently only regulated by passive controls that regulate the dose incorporated within the patch. Their control is usually not based on electronic communication, but rather on the diffusion properties of the membranes and patches and formulations. The device of the present invention provides a means for a remote operator to adjust the dose and timing of drug delivery while the patient is walking.

Another object of the present device is to provide a patient data communication system for world wide patient re-programming telemetry using a medical device worn by the patient. .

The device described herein is a formulation-containing transdermal patch with or without enhanced permeability by electromagnetic energy. However, the invention is not limited to transdermal drug delivery and may include communication with an implanted drug delivery device using the aforementioned electromagnetic energy based delivery techniques.

The devices disclosed herein transmit and receive code information from remote or on-site information sources. The operator of the device can be located at a location and communicate information from the medical support network. The device includes: a wireless interface including a controller telemetry transceiver for transmitting and receiving code information between the system controller and the device telemetry transceiver; providing positioning data to the system controller to identify the patient's global position. A global positioning system coupled to a system controller; a communication means for communicating with a remote medical support network; and a communication means for transmitting positioning data to the medical support network and instructions from the medical support network. A communication network interface means coupled to the system controller and the communication means for selectively making available the communication means for selectively receiving. The communication interface may include the ability to transfer data between the patient and the operator via a cellular network, paging network, satellite network, wired telephone network, or modem-based network, including the Internet. Absent. As communication
Examples include, but are not limited to, macro waves, radio waves, and digital communications via optical means. Communication and monitoring systems provide a means for exchanging information and exerting control over one or more medical devices attached to the patient's body. It is expected that the device will function no matter how geographically the patient is associated with the monitoring location or medical support network. An operator, usually a physician, types in a code, which is transmitted via a medical support network to a patient whose location can be located by a survey satellite or in connection with another telecommunications network. The code includes information that activates the device and further controls the dose.

Transmission of data between the operator and the device is performed by a control device that transmits data via a communication network. The telemetry antenna and corresponding transmitter / receiver can both download and upload data. The antenna can function in radio waves. Control of the dose on the device itself is provided by a digital controller / timer circuit having corresponding logic circuits coupled to the microcomputer. The microcomputer controls the arithmetic functions of the digital controller and the timer. The microcomputer specifies the start, timing and duration of the event. Microcomputers rely on microprocessors and corresponding R, depending on the requirements for additional memory and programmable functions.
Includes AM and ROM chips.

The base station can be at the location of the operator. The base station is a microprocessor-controlled computer having hardware and software;
And may include a corresponding modem for the transmission of information relayed over a suitable communication network. Also, the system controller may be connected to a GPS receiver for receiving positioning data from the satellite. GPS receivers can use currently available systems.

Example 10 Bar Code Indication A bar code symbol can be used by a pharmaceutical manufacturer or pharmacy to encode a dose schedule for a drug. You can edit the coded barcode symbol on one or more menu sheets that are readily available at the doctor's office or pharmacy counter where the controller is located. In such an application, a barcode symbol reader may be coupled to the data communication port of the medical support network and placed on a patch and used to program the device with the appropriate dose. The code can be transmitted to the device carried by the patient via the Internet or other telecommunications network, after which the patient can read the barcode in the patch.

All patents or publications mentioned in the specification are indicative of the levels of those skilled in the art to which the invention pertains. These patents and publications are to be read as if the individual publications were specifically and individually indicated to be incorporated by reference.
Which is incorporated herein by reference.

Those skilled in the art will readily appreciate that the invention is well adapted to achieve the objects of the invention and to obtain the above-described results and advantages as well as essential results and advantages. This example, together with the methods, procedures, procedures, molecules, and specific compounds described herein, are presently representative of preferred embodiments, are exemplary, and are not intended to limit the scope of the invention. Variations and other uses of the invention will occur to those skilled in the art and are within the scope of the invention as specified by the claims.

[Brief description of the drawings]

FIG. 1 shows a transdermal patch that includes an electromagnetic energy controller, electrodes for transmitting energy, a drug reservoir containing the formulation, and an adhesive support for adhesion to the skin.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 45/00 A61K 45/00 4C206 A61M 35/00 A61P 23/00 A61P 23/00 29/00 29/00 31/00 31/00 35/00 35/00 43/00 121 43/00 121 G06F 17/60 126N G06F 17/60 126 A61M 35/00 (81) Designated countries EP (AT, BE, CH, CY, DE , DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML) , MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, Z, MD, RU, TJ, TM), AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV , MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, UZ, VN, YU, ZA, ZW (72) Inventor Flock, Stephanty 3930 Victoria, Australia Mount Eliza Gillards Road 17 F-term (reference) 4C053 BB34 4C076 AA09 AA73 AA81 AA95 BB21 BB31 CC01 CC04 CC27 CC31 CC37 EE60 FF 4C084 AA17 MA05 MA56 MA63 NA11 NA13 ZA082 ZA891 ZB112 ZB262 ZB322 ZC751 ZC752 4C086 AA01 DA03 MA02 MA04 MA56 MA63 NA13 ZA04 ZB11 ZB26 ZB35 ZC71 ZC75 4C167 AA71 AA72 BB41 BB42 BB46 BB48 CC01 DD10 4C206 AA76 MAB MA01 GA04

Claims (23)

[Claims] 1. A method for controlling the transport of a pharmaceutical compound in a subject, the method comprising: irradiating the subject with electromagnetic energy; and providing the pharmaceutical compound to the subject. Wherein the compound is included in a patch. 2. The method of claim 1, wherein said electromagnetic energy is selected from the group consisting of radio waves, microwaves and light. 3. The method of claim 1, wherein the patch is implanted in the subject or locally located in relation to the subject. 4. The method of claim 3, wherein the patch is controlled on site or remotely by an external controller. 5. The method of claim 4, wherein said controller is a microprocessor. 6. The method of claim 3, wherein said patch is made of a material selected from the group consisting of a bandage material, a gel, a viscous material, and an adhesive material. 7. The method of claim 1, wherein said pharmaceutical compound is selected from the group consisting of an anesthetic, an anti-tumor drug, a photodynamic therapeutic, an anti-infective, and an anti-inflammatory. 8. The method of claim 7, wherein said anesthetic is lidocaine. 9. A system for controlling a rate of drug transport or biomolecule collection in a subject, the system comprising: means for producing electromagnetic energy; means for supplying the electromagnetic energy to the subject; Means for administering the drug to an individual or collecting biomolecules from the subject, wherein the drug is included in a patch that is controlled on site or remotely by an external controller. And the system. 10. The system of claim 9, wherein said electromagnetic waves are selected from the group consisting of radio waves, microwaves and light. 11. The system of claim 9, wherein said means for producing electromagnetic energy is selected from the group consisting of a laser and an ultrasonic transducer. 12. The system according to claim 9, wherein said controller is a microprocessor. 13. The system of claim 9, wherein the controller is powered by a dry cell, solar cell, electrochemical generator, thermal energy generator, or piezoelectric generator. 14. The system of claim 9, wherein the patch is implanted in the subject or is locally located in relation to the subject. 15. The system of claim 9, wherein the patch is made of a material selected from the group consisting of a dressing material, a gel, a viscous material, and an adhesive material. 16. The system of claim 9, wherein said patch includes one or more reservoirs separated by one or more rupturable membranes. 17. The multi-reservoir-containing patch stores an unstable pharmaceutical compound,
Here, the lyophilized crystalline portion of the pharmaceutical compound is stored in a first reservoir, while
17. The system of claim 16, wherein the liquid portion of the compound is stored in a second reservoir. 18. The system according to claim 17, wherein said pharmaceutical compound is prostaglandin E1. 19. The system of claim 9, further comprising an electrode, wherein the electrode is in contact with both the patch and a controller. 20. The system of claim 19, wherein said electrodes transmit current or electromagnetic radiant energy. 21. The system of claim 9, further comprising a computer monitor connected to the Internet, wherein the signal is routed through the Internet, via the computer monitor, and into the patch. Item 10. The system according to Item 9. 22. A patch for drug delivery or biomolecule collection, wherein the patch is monitored by a computer by a global positioning system. 23. The patch according to claim 22, wherein said global positioning system is a global positioning satellite receiver.