Endermic medicine applicator

Description: TECHNICAL FIELD [Detailed description of the invention]

【0001】

[Industrial application field]

The present invention relates to a transdermal drug applicator and an electrode configuration used with the applicator, and more particularly to a drug applicator that is attached to a control system and has an action relationship with animal or human skin. Further, among these, the present applicator is particularly related to the one arranged in the watch body.

【0002】

[Conventional technology]

Conventionally, as a method of administering a drug, there has been a method of supplying the drug through the skin of an animal or a human using electrophoresis or electroosmosis. This is to supply drug molecules into the body by causing the drug molecules in the solution or suspension to receive an electric field. In the case of electrophoresis, when an electrode with the same charge as an ion molecule is on the solution adjacent to the skin where the dosing is done, the ions repel and move through the skin into the blood stream. On the other hand, in the case of electroosmosis, the aqueous solution is attracted to the negative electrode and generates an electric current through the porous membrane. Both have similar end effects, but such electrochemical processes are used separately or independently to inject or deliver the drug or other drug percutaneously. It can be carried out. These types of transdermal drug applicators supply the drug by passing an electric current through an electrical circuit formed containing the drug reservoir and the patient's skin. According to such an applicator, the drug supply to the patient is best performed at a constant rate for a long period of time or on demand while maintaining a stable state. As such a device, US patents 385,556 and 486,902 , 588,479, 2,493,155, 2,267,162, 2,784,715, 3,163,166, 3,289,671, 3,547,107, 3,677,268, 4,008,721, 4,141,359, 4,239,046, 4,166,457, 4,239,052, 4,290,878, 4,164,226, 4,362,645, 4,273,135, 4,243,052, 4,325,367, 4,367,745, 4,419,091, 4,474,570, 4,406,658, 4,314,554 and, Other foreign patents include EPA 0060452, DE 290202183, DE 3225748, EPA 0058920, and UK 2104388.

【0003】

[Problems to be Solved by the Invention]

However, the beneficial effects of drug administration are diminished if the patient sometimes forgets to activate the drug delivery mechanism. Therefore, drug supply is often done in hospitals. On the other hand, if the patient operates the supply mechanism without permission, it is expected that the drug supply will be irregular. For this reason, there is a problem that the drug may be forced to go to the hospital or there may be a risk of misuse even though the drug is originally supplied automatically. Therefore, a main object of the present invention is to attach the drug applicator to the patient's skin and automatically predetermine or pre-program the power supply up and down times at variable controlled speeds. It is to provide a system for supplying and stopping a drug by electrophoresis or electroosmosis injection at regular time intervals. Another object of the present invention is to attach one or more drug reservoirs to the patient's skin and to perform electrophoresis and / or electroosmotic injection at a controlled rate at predetermined time intervals to obtain one or more drugs. It is to provide a system including a computer mechanism that can be programmed to signal the activation and deactivation of a power source that is installed to supply and deactivate the supply. Other objects of the invention include responding to physical and chemical changes experienced by a subject or patient by providing a closed-loop feedbag system or by providing a drug delivery system that is actually on demand. The purpose is to provide a system that responds to drug supply control to patients.

【0004】

[Means for solving problems]

In order to achieve the above object, the transdermal drug applicator of the present application is a transdermal drug applicator attached to a living body in order to supply at least one drug into the blood flow through the skin or the like, and the above drug is physically / chemically applied. With an applicator means having at least one drug reservoir that houses the drug for feeding through the skin by mass transfer; removable to the living body to hold the applicator means detachably fed to the attachment means. With the attachment means to be attached; with the power supply means for the applicator means; for applying power received from the power supply means to the applicator means to form an electrical circuit between the applicator means through the skin. With circuit means; receive a programmed command for the drug, send a signal to the drug, send a programmed command to the power supply means to generate electricity and the drug through the skin. Percutaneous drug applicators comprising computer means associated with the attachment means are provided to regulate supply.

【0005】

[Example]

Next, examples of the present invention will be described with reference to the drawings. FIG. 1 is a diagram showing an operating principle of the transdermal drug applicator according to the present invention. Referring to FIGS. 1 and 2, the applicator 10 consists of a jacket 12 having a raised portion 14 and an edge portion 16 along the outer circumference. The applicator 10 can be formed in any shape or size as long as it has a central portion of the ridge accommodating other electrophoresis units and electroosmosis units described later and an edge portion along the outer circumference thereof. For example, it can be made into an arbitrary shape such as a square, a rectangle, an ellipse, a circle, etc. according to a specific place on the skin. As can be seen in FIG. 2, here the applicator 10 is attached to the surface of the patient's skin 18, but within the raised portion 14 of the jacket 12, there are multiple layers described below. The first layer is a microporous or semipermeable membrane 22 through which the drug to be fed travels through the skin 18. The membrane 22 is not necessary depending on the nature of the drug reservoir.

【0006】

The second layer consists of a flexible pad or other type of reservoir 24 that contains the drug to be administered. As can be understood from the art and as shown in one or more of the United States patents above, the reservoir 24 is an impregnated pad or gel containing the selected agent in a solution or suspension. Is also good. Also, the walls are dense enough to prevent drug leakage under ambient conditions, but when electrophoresis is used, such as charged particles or ions under the influence of the electric field formed. It is porous enough to allow the movement of the drug. For example, if leakage occurs under ambient conditions as a result of applicator stuffing for transport or storage, temperature fluctuations and punctures in the reservoir, it is appropriate to employ microporous membranes. In this case, whether or not to use the membrane 22 and what kind of membrane to use depends largely on the nature of the drug used. Further, the reservoir 24 may be made of a porous substance impregnated with a drug rather than a pouch containing a liquid drug.

【0007】

The third layer on the reservoir 24 is an extension contact 26 that can be incorporated as one side of the battery 28, which is the next layer. The contacts 26 are preferably made of any conductive material, preferably one that allows the applicator 10 to fit snugly against the surface of the skin. Suitable properties of this type are well known in the art and include conductive, preferably nonionic polymers. Carbonated or surface metallized plastics can also be used for this application.

【0008】

The battery 28 that constitutes the next layer can consist of a group of cells that are internally connected in series to obtain the desired voltage required to obtain electrokinetic action for a particular drug. The orientation of the battery 28 depends on whether the charged particles of the selected drug are positive or negative. If the particles are negatively charged in solution or suspension, the contact 26 is connected to the negative side of the battery 28 because the skin becomes positive with respect to the contact 26 and attracts ions. For electro-osmosis, for example, the pH of the drug solution is less important, so it is more flexible in design and structure. In addition, the solvent can be concentrated to a fairly high concentration. This is in contrast to ionic solutions, which require high ionic fluidity and lower concentrations. Therefore, both types of drug supply systems are considered here. Although these are within the scope of the invention, the system utilized should be based on the drug of choice. Both systems can be combined. They can also be used simultaneously to maximize the efficiency of the outcome or to supply nonionic agents or increase the rate of supply.

【0009】

The battery 28 can be arranged and connected in series using any conventional small battery cell currently generally available to obtain the desired working voltage. In addition, batteries are now being developed that are made of extremely thin and flexible conductive polymer sheets that have a large surface area relative to their thickness in order to provide adequate current densities. One such so-called plastic battery is described in "Battery Today", Autumn 1981, pp.10, 11 and 22. When using such a battery, the sheets can be stacked so that the cells are arranged diagonally in series, as shown somewhat schematically in FIG. Of course, the battery is finally selected after considering factors such as the desired degree of copying, the voltage and current density required for a specific application, and the discharge time. On the battery 28, another contact 32 having the same configuration as the contact 26 and electrically connected to the opposite side of the battery 28 is superposed.

【0010】

The jacket 12, which encloses all layers of the applicator 10, is formed from a flexible conductive plastic material such as a carbon-impregnated polymer or surface metallized plastic. The insulating material 34 fills the space between the side wall of the raised portion 14 and the various layers contained therein.

【0011】

A conductive adhesive material 36 is applied to the underside of the edge 16 so that the applicator, or device 10, is placed on the skin 18 and adhered to provide good electrical contact.

【0012】

Roughly speaking, the above configuration forms a complete electrical circuit from one side of the battery back to the jacket 12, the adhesive material 36, the skin 18, the microporous membrane 22, the reservoir 24 and the battery 28. To. The configuration of the electric circuit formed by the above configuration is shown in FIG. In FIG. 3, the circuit is schematically shown by numbers corresponding to the structures shown in FIGS. 1 and 2.

【0013】

The battery 28 is connected to the skin 18 via the contacts 32, the jacket 12 and the adhesive layer 36. The other side of the battery 28 is connected to the skin 18 via a contact 26, a reservoir 24 and a membrane 22 to complete the circuit. The resistor Reff represents the effective resistance of the complete circuit including the skin 18, the adhesive layer 36, the jacket 12, the battery 28 and its contacts 26 and 32, along with the reservoir 24 and the membrane 22. In this type of system, one of the aims is to create a very low specific current flow so that the drug injects slowly over a long period of time. 0.0001 A / cm of skin surface under membrane 22² The low current is the typical current chosen to administer a particular drug. The electrical resistance of the skin to electrical current is on the order of 6-9 KΩ and is roughly independent of the distance between multiple points on the skin where electrical contact is made. This is because the electrical resistance of the skin is mostly resistance to the entry of electric current into the body, and the electric current flows through the fluid in the body where the electrical resistance is extremely low. Thus, in order to produce the current at the indicated speed, according to Ohm's law, the total resistance of the circuit using the 1.5V battery is about 360KΩ per square centimeter of the affixed part. This resistor, the effective resistance of the circuit, Reff, can be made by combining one component or the components of the circuit shown in FIG. 3, including the battery resistance, electrodes, jacket material, and the like. In addition, if desired, a constant current limiting device, such as a conductor 26, may be useful in order to keep the current constant throughout the operating time of the applicator. It can be formed integrally with and as part of any other part of.

【0014】

Further, as schematically shown in FIG. 4, the applicator 10 can incorporate a device to ensure that the infusion of the drug is stopped after a predetermined time or after a certain amount of drug has been administered. .. This can be achieved by using a programmable integrator circuit or by inserting an integrator such as reverse plated cell 38 into the circuit. As is known in the art, cell 38 consists of a pair of electrodes, one of which has a coating of material to be transferred to the other electrode. When the total plating material adheres after a predetermined time elapses based on the thickness of the original coating film or an integrated current representing a desired amount of the drug to be donated flows, the internal resistance increases significantly. This reduces the amount of current and results in the cessation of drug transfer. Such a device can be used to predetermine the duration of application of the drug, or, as described above, the amount of drug to be donated. Cell 38 is a relatively high resistance device and can provide much of the high resistance required for the action of the applicator 10.

【0015】

The cell 38 can be made as part of the contact 32 or can be inserted between the contact 32 and the outer cover material 14. Furthermore, it is possible to create a device for gradually passing an electric current so as not to give a feeling or sensation to the person receiving the drug.

【0016】

1 to 4 show the structure of the device 10 and the liquid crystal display (LCD) 50 incorporated in the circuit. The display state of the LCD 50 changes only at a constant specified current of the device 10. That is, the prescription dose of the drug is percutaneously administered to the user by such a completed circuit through which a constant current flows, and the LCD displays an optical display to positively display the drug administration status. LCD in case of (1) circuit disconnection where the conductive edge comes off the skin surface, (2) battery exhaustion or its failure, or (3) drug depletion that causes a shortage of constant current The liquid crystal display changes to inform the user that the drug is not being administered as prescribed. In this way, the user is given a clear and positive indication of whether the drug is being properly administered or not. If the drug is not properly administered, the user simply removes the device and installs a new one. At the same time as the new installation, the new LCD is activated. A light emitting diode (LED) can also be used instead of the LCD. With the indicator 50, a complete circuit is formed by the skin 18, the adhesive layer 36, the jacket 12, the battery 28, the indicator 50, the contacts 32 and 26, the filled reservoir 24, the membrane 22 resistor Reff. As will be described later, a digital or analog programmable computer display may be used to indicate the drug administration status. In this case, the device gives the patient an audible or mechanical (vibration) warning in the event of a malfunction such as loss of skin contact or weak battery.

【0017】

With reference to FIG. 5, an enlarged cross section of another Example 60 for the indicator 50 is shown. The display 50 is composed of upper and lower layers 61 and 62 of a conductive polymer. Layers 61 and 62 form a reservoir 63 with an end cap (not shown) of the non-conductive polymer. The upper layer 61 has at least one transparent portion or is completely transparent. Then, a solution or a gel 64-like electrochemically conductive phototropic material is placed in the reservoir 63. Further, one layer of silica fine particles 65 is arranged in the reservoir 63 to form a non-conductive layer between the layers 61 and 62. Leads 66 and 67 are also provided to complete the circuit with the battery and contacts 24, respectively.

【0018】

Electrochemically phototropic or electrochromic materials change color or appearance as a result of the passage of electrical current through the material. The reservoir 63 is filled with a color changing material that is visible to the user through the transparent upper layer 61 of the device. Suitable electrochemically phototropic materials include, for example, the ion change sensitive labeling dye disclosed in United States Patent No. 4,013,414, granted to Lavalry et al. On March 22, 1977. By providing the display of the present invention with a highly polar state, the dye color change of the ion change sensitive display as described above is detected, thereby informing the patient that the drug is being administered.

【0019】

A chemical or dye material that responds to or bends in color due to changes can also act as a display by using the constant current of the device to cause changes in color or tortuosity. Suitable dye materials are, for example, those disclosed in United States Patent No. 4,362,645, granted December 7, 1982 to Hoff et al.

【0020】

The applicator 10 is preformed in various sizes and shapes, sealed in a plastic pouch, and a protective strap is hung on the exposed side. Various agents can be incorporated for a particular application and the battery can be varied depending on the amount of current required. Of course, the electrical orientation of each battery is determined by the drug. When using the device, remove the protective cord and place the applicator on the desired skin, such as behind the ear, or in contact with the mucous membranes. When the applicator is placed in this way, an electric current flows, and at the same time, the movement of the drug is started.

【0021】

By using the inventions described herein, it has become possible for the first time to perform long-term drug treatment with considerable control and accuracy, which was previously impossible or impractical. The cost of treatment using the present invention can be sufficiently reduced due to the effect that the treatment can be economically carried out by widely using the present invention. The indicator also gives the user a positive guarantee that was not previously available in the drug dispenser that is inserted into the body.

【0022】

On the other hand, a circuit configuration as shown in FIG. 6 may be adopted, and a third electrode 86 that feeds back the signal to the amplifier 94 in a loop may be provided. This third electrode 86 is used as a control prog that senses the need for drug administration. Here, 76 is a microporous membrane, 78 is a reservoir, 82 is a battery, 87 is the surface of the third electrode 86, 90'is the skin, and 92 is the adhesive. Such electrodes or proses are, for example, conventional, ion-sensitive, as appropriate, with the appropriate enzyme on the surface 87 to detect the particular drug in the body or blood in order to regulate the particular drug. It is fixed. The drug may be, for example, sugar, insulin, or any other element that one wishes to detect to determine a particular drug requirement. Thus, with a simple feedback loop circuit, the generated amplified signal can be used to achieve a demanded drug delivery system, which allows drug administration to be controlled to some extent by request. Become. The enzyme used can detect the concentration of certain drugs in the body that you want to control. Due to enzyme detection and detection of specific drugs in the body, the charges and signals generated in the electrode prog are amplified as much as necessary to give control signals to the applicator battery circuit to regulate drug administration to the desired level. To. Of course, the electrodes incorporate certain semiconductor and / or field effect transistors that receive, amplify, and transmit the signal measured by the prog.

【0023】

Alternatively, the detector 86 may be capable of detecting various body parameters that can be detected directly or indirectly in the skin or mucous membranes. Examples of these body parameters include skin temperature, skin conductivity, pulse rate, capillary dialation, and the like.

【0024】

Referring to FIGS. 7 and 8, a side-by-side patch or drug applicator 100 structure is shown anchored to skin 102. As shown in the figure, the element 104A shows the first electrode and is separated and separated from the second electrode by an appropriate space including an air gap. As best shown in FIG. 7, the gap is appropriately shown as a "weir" 106 that can be made from an impermeable, non-conductive material such as silicone. The weir 106 can maintain electrode separation and eliminate any "short-circuit" effects between the electrodes that can be caused by sweat or other moisture that accumulates under or adjacent to the weir or electrode barrier means. Give a seal to the skin so that it can be done. Element 108 is a covering material similar to the jacket 12 of FIGS. 1 to 2. However, this encapsulation material is such that the electrodes or battery 110 and the constant current device 112 connected in series (which can optionally be configured from a constant current diode) are placed on the first and second electrodes by leads or conductors. It does not have to be conductive as it is appropriately connected to separate conductive terminals or film elements 114A and 114B, respectively. Preferred elements can be made from carbonized plastic foil or other conductive film such as metallized mylar.

【0025】

The membrane 116 placed along the bottoms of the first and second electrodes is a semipermeable microporous property that is optional, as in element 22 of FIGS. 1-4, and has adhesive and preferably gel-like properties. Consists of membrane elements. The weir 106 is preferably a suitable impermeable insulating material that projects beyond the membrane 116 and is formed to form an effective weir-like seal between the separation electrodes forming the applicator device. As described above, the weir 106 must be not only impermeable to chemicals, water, etc., but also non-conductive.

【0026】

The drug matrix can also consist of a reservoir. The second electrode 104B is disposed between the microporous inferior membrane 116 and the conductive element 114B. On the first electrode of the applicator patch 100, an appropriate drug matrix or reservoir 118, such as a low concentration electrolyte solution, is placed between the non-porous membrane 116 and preferably the other semipermeable membrane upper membrane 120. And form another (upper) high concentration drug matrix or reservoir 122. The above configuration for the first electrode of the patch facilitates the maintenance of a predetermined gradient concentration and desired pH to aid in optimal drug administration.

【0027】

In FIG. 9, which shows the electrical outline of the present invention, the number 124 indicates the current flow generated by the power supply or the battery 110 as a virtual line. In addition, this figure schematically illustrates yet another applicator structure or modification consisting of three separate electrodes, all of which are "active" electrodes or drug reservoirs with similar internal structures, where the three electrodes are numbered. Identified by 126A, 126B and 126C.

【0028】

Reference arrow A from reservoir 126A, for example skin 102, is used to percutaneously supply the drug by electroosmosis. On the other hand, the reference arrows B and C, which exit the reservoirs 126B and 126C and reach the skin 102, respectively, can be used to percutaneously supply positive and negative ions, respectively, by ion electrophoresis or electrophoresis.

【0029】

The device of the present invention can use some or all electrokinetic phenomena for drug administration through the skin, such as electroosmosis, electrophoresis and ionphoresis. It should also be recognized that electro-osmosis displaces the liquid from the positive electrode to the negative electrode and such mass transfer processes are less dependent on the concentration level of the drug. On the other hand, ion electrophoresis occurs on either positive or negative electrodes and generally requires low concentrations and high dilutions with a controlled pH.

【0030】

Therefore, as described above, although FIGS. 7 to 9 show different electrode structures, both sides may have the same structure. Therefore, as shown in the figure, the left side is the inert electrode and the right side is the inert electrode. In contrast to the active electrode, both sides are composed of "active" electrodes. According to such an applicator structure, one or both sizes can deliver the iontophoretic drug on one side of the patch and electroosmoticly on the other side. In addition, the electrochemical parameters can be configured and arranged so that multiple electrokinetic phenomena occur simultaneously or sequentially on the same electrode. The passage of electrical current through the device causes physical and chemical changes, both within the patch and at the skin level, which prevent or inactivate one of the thermodynamic mechanisms of drug supply and. The other thermodynamic phenomenon can be activated. Such physical and chemical changes can be used to change the drug delivery rate in a time-dependent manner without changing the current.

【0031】

As clearly shown in FIG. 7, the electrodes can be manufactured to the same size and / or shape for convenience, but they do not necessarily have to be the same size (or shape). Similarly, although the peripheral element 128 at the bottom acts as an adhesive seal boundary around the periphery of the applicator similar to element 34 in FIG. 2, these electrodes and applicator structure are actually shown in FIGS. It does not incorporate a true "edge" region or skin electrode like the device in 4.

【0032】

The above-mentioned features of the transdermal drug applicator according to the present invention are attached to the body of a patient, which is shown as an exploded perspective view in FIG. 10 and a perspective view in FIG. It is incorporated into a computerized control and mounting system 130, which is shown as a bracelet or a bracelet. Figure 10, showing the invention upside down for clarity, contains three parts: a long stretched drug applicator 134; a watch body 136 that houses the control and power elements of the system; and the system. The strings that hold down the watch, in particular, the string buckle portion 138 and the string buckle reservoir 140 that are fixed to both sides of the pair of the watch body 136, respectively. Applicator 134 is part of the drug applicator system to be described. The upper side of the applicator 134 is detachably supplied to the bottom side of the watch body 136 and the bottom side of the string portions 138 and 140 by an adhesive layer 141 exposed by removing the covering lining sheet 142 from the upper side of the applicator 134. To. The bottom side of the applicator 134 adheres tightly to the patient's skin 144 as shown in FIG. The applicator 134 is formed in the shape of the watch body 136 and its string. As shown in FIG. 12, the lace buckle portion 138 has a buckle 146 and a tongue 148 coupled to the end of the buckle portion, the tongue 148 being inserted into one of a series of holes 150 in the lace buckle reservoir 140. It has become so. 12 and 13 show a liquid crystal display (LCD) 152 displaying a digital readout of time.

【0033】

12 and 13 show the internal shapes of the watch body 136 and the applicator 134. The inside of the watch body 136 will be described first. The watch casing 154 encloses the watch body 136, except for the display window 156 located at the top of the watch body 136 and other holes described later.

【0034】

The upward-facing liquid crystal display (LCD) 152 occupies the top layer of the watch body 136 just below the window 156, and the computer component 158 occupies the layer just below the LCD 152. Computer component 158 includes a hardware computer component designed to provide special program instructions related to the percutaneous application of the agent contained in the applicator patch 134. Buttons 174 and 176 are attached to one of the sides of the watch body 136, which joins to the side where the straps are joined , and buttons 178 and 180 are attached to the opposite side. Buttons 174, 176, 178, 180 are designed to control the programs contained in computer component 158. FIG. 10 shows the placement of the holes 160 adjacent to the control buttons 174 and 176, which are designed to receive the fork of the plug 162. The plug 162 is coupled to a pre-programming system (not shown) provided by the doctor's office. The watch battery 164 is located in the layer immediately below the computer component layer 158. The applicator battery 166 is located in the layer just below the watch battery. The applicator battery 166 is associated with the applicator patch 134 to power the drug applicator system just described. The feedback electrode 168 (such as the feedback or detector electrode 86 described above in connection with FIG. 8) is appropriately located just below the applicator battery 166 and in the center of the watch body 136. A hole formed in the bottom of the watch casing 154 provides access to electrode contact with the applicator's battery 166.

【0035】

As shown in FIG. 13, the drug applicator comprises opposing positive and negative applicator patches 182A and 182B, which are described on the positive and negative sides of the applicator battery 166, respectively, as shown. By being electrically connected to each other, they function as positive and negative electrodes. As best shown in FIG. 12, the two separate drug pouches 186A and 186B have string covering means 138 and 140 on the positive and negative patches 182A and 182B of the applicator 134, respectively. The non-conductive neutral portion 190 in the middle of the applicator 134 separates the positive and negative patches 182A and 182B. The positive and negative reservoirs 186A and 186B have the same high concentration upper layers 192A and 192B as the specific one or more drugs and the low concentration virtual 194 and 194 of the same one or more drugs, respectively. The reservoirs 186A and 186B may each contain different agents or may each contain the same agent. Alternatively, the drug may be contained in only one of the patches, and the other patch may contain a non-drug property that acts as an electrode with a charge opposite to that of the drug patch. The upper layers 192A and 192B are separated from the lower layers 194A and 194B by the semipermeable membranes 196A and 196B, respectively. The lower part of patches 182A and 182B is a microporous or semipermeable membrane 198A and 198B similar to the membrane 22 described above with respect to FIGS. 1 and 2, through which the drug migrates to the skin 144. Absorbed through.

【0036】

The flexible conductive layers 200A and 200B extend between the positive and negative reservoirs 186A and 186B, respectively, and the positive and negative terminals of the programmable controller or computer 158. The conductive layers 200A and 200B are preferably disposed approximately in the middle of the lower layers 194A and 194B, respectively, and extend from the positive and negative electrode positions from the reservoirs 186A and 186B to the neutral or central 190. The highly conductive connectors 204A and 204B at the neutral portion 190 connect the inner ends of the mesh layers 200A and 200B to the positive and negative terminals of the programmable computer 158 by conductors 206A and 206B embedded in the top of the watch casing 154, respectively. To do.

【0037】

The applicator system can house a negative ion drug in the negative reservoir 186B and a positive ion drug or a neutral ion drug that acts by electroosmosis in the positive reservoir 186A. The conductive layers 200A and 200B are preferably made of conductive carbon fibers woven with conductive hair-like protrusions coming out of the woven fabric. Alternatively, the flexible layers 200A and 200B are made from flexible conductive strands with the addition of conductive carbon particles. Applicator Battery 166, Programmable Computer 158, Conductive Mesh Layer 200A, Membrane 196A, Reservoir 186A, Patient Skin 144, Membrane 196B, Reservoir 182B, Conductive Mesh Layer 200B, Connector 204B, Conductor 206B, Computer 158, and The electrical circuit leading to the other terminals of the applicator battery 166 is formed in this way. The connections between batteries 164 and 166 and computer 158 are not shown for ease of illustration. When a negatively ionized drug is supplied to the negative reservoir 186B, the drug is repelled from the negative charge to the patient's skin 144 by iontophoresis.

【0038】

When the positive patch 186A is supplied with a positively ionized drug, the drug is repelled from the positive side through the patient's skin 144 by iontophoresis. Alternatively, the positive reservoir 186A can also supply a neutral drug such that the drug is transferred into the patient's skin 144 by electroosmosis.

【0039】

The opaque seal layers 202A and 202B extend over the top and outside and edges (not shown in FIG. 13) of patches 182A and 182B to partially wrap the high concentration reservoirs 192A and 192B, respectively. Exists. Layers 202A and 202B feed the non-conductive central 190 and the semipermeable bottom membranes 198A and 198B to completely enclose the drug reservoirs 186A and 186B. The adhesive layer 141 is secured by an adhesive (not shown) to the upper side of the sealing layers 202A and 202B and the non-conductive neutral part 190, and further to the lower side of the strap coverings 138 and 140 and the watch casing 154. Ru. The watch body 136 and the straps 138 and 140 can be removed from the applicator 134 so that the watch body 136 can be reused.

【0040】

The third or feedback detector 168 is in electrical contact with the programmable computer 158, as best outlined in FIG. As can be seen in FIG. 14, the leads 208A and 208B have the positive and negative patches 182A on the positive and negative sides of the battery 166 and programmable computer 158 (in FIG. 14 as the current regulator 210 and programmer 212, respectively). Electrically connected. Lead 216 connects a third feedback detector 168 to programmable computer 212. Current from the power supply or battery 166 is lead wire 208A, drug reservoir 182A, skin 144, drug reservoir 182B, It returns to the battery 166 through the lead line 208B, the programmable controller 212, and the current regulator 210. The detector 168 has a skin control unit 218. The contact layer 218 detects changes in the patient's skin, eg pH. It may be a sensor or an ion-sensitive electrode. Layer 218 has the ability to send the detected changes to the third electrode 168 and is capable of detecting chemical or physical changes on the surface of the skin 144. The 168 feeds the loop signal back to the programmable computer or controller 212 via the lead 216. Detecting a drug request and signaling this request to the controller is a key function of the feedback detector 168. The vessel 168 is preferably ion-sensitive, and layer 218 can be provided with suitable enzymes to detect specific drugs to be regulated in the body or blood. Sugar and insulin are typical to be regulated. This is an example of a chemical.

【0041】

Next, other specific examples according to the present invention will be described. FIG. 15 is an exploded perspective view showing an outline of the configuration. FIG. 15 shows an embodiment of the present invention in which a refillable applicator or patch is disposed within the watch body. The patch reservoir may be part of a waste cartridge that is refillable or can be disposed within the watch body.

【0042】

The applicator system 340 includes a watch body 342 with an LCD 343 and a computer assembly and computer battery similar in operation to a computer 158 and computer battery 166 similar to those shown above (neither shown). And are provided. Although the watch body 342 is shown as cylindrical for convenience of description, it may have any other shape, for example a square or rectangle as shown in the embodiments described above. The drug reservoir 344 has a microporous membrane 348 that contacts the patient's skin 350. The drug contained in the reservoir 344 is supplied through the patient's skin 350. The reservoir 344 can be formed into various shapes. The reservoir 344 has an outer cover 352 and an outwardly extending circular lower edge or conductive flange 354 that comes into contact with the skin 350. The applicator battery 356 is arranged in the watch body 342 over the reservoir 344. The applicator battery 356 has opposite top and bottom electrical contact layers 358 and 360. A conductive adhesive layer (not shown) under the outer edge of the flange 354, such as the adhesive 36 in FIG. 1, has a current shown by virtual line 364, which is a semipermeable membrane 348, skin. It is provided to flow from 350 and flange 354. Of course, in this embodiment of the present invention, the programmable computer (not shown) and current adjusting means described above may be used in a similar manner for controlling drug supply.

【0043】

In this embodiment, as shown in FIG. 15, the rimmed hat-shaped assembly can be removed from the bottom of the watch body 342 by the method of a cartridge. The flange portion 354 serves as the bottom wall of the watch body 342 when it is attached to the watch body during use. The current 364 flows as soon as the membrane 348 is placed on the skin 350. The cartridge can be appropriately fixed to the watch body by various means such as a claw provided around the flange portion 354 or by a snap-on connector. The strings 366 and 368 may be integrated with the watch body 342 as shown or may be attached separately to the watch body. A switch actuating cam 369 extending upward from the upper wall of the reservoir 344 is fitted with a plurality of recesses in the watch body, and a programmed response is actuated within the programmable computer. The position of the switch actuating cam 369 is predetermined by the type of drug contained in the reservoir 344. Alternatively, a conductive bar code 371 appropriately provided in front of the reservoir 344 can be used to activate a programmed response according to the drug contained in the reservoir.

【0044】

Another embodiment for replenishing the drug from the reservoir includes an elongated filling tube 370, as shown by the imaginary line in FIG. The top surface 372 has an LCD 343. The filling tube 370 has a self-sealing top cover 376 made of rubber or a similar substance that can be penetrated by the needle of the syringe 378, indicated by a virtual line, to contain the refills of the depleted drug in the reservoir 344. There is.

【0045】

An example of a monitoring device that can be combined with a programmable computer included in the watch body may be a heart rate measuring device. Such devices are well known and old, for example, in that Jogger watches can use LEDs and phototransistors to measure heart rate (pulse) and thermistors to measure skin temperature. Is. A light emitting diode (LED) is placed inside the watch body on a vertical light tube formed in the neutral portion 190 of the applicator. The bottom opening of the tube is in direct contact with the patient's skin, the light reflected from the skin is measured by a photocell (not shown), and the change in reflected light is used to calculate the pulse rate.

【0046】

The mounting means is not limited to the following structure, but can take any appropriate configuration including this. That is, it can be a headband, an arm or leg band, a bracelet or a watch string, a body belt, or the like. The applicator is disposed between the attachment means and the skin or mucosa, but other configurations include tampon-like inserts or similar devices used in the vaginal or human body cavities. According to such a configuration, the applicator means may be detachably or permanently attached to a core element, which may include some of the elements of the device, and the applicator means itself is actually It may be arranged or wrapped around the core.

【0047】

[Effect of the invention]

As described above, according to the transdermal drug applicator according to the present invention, by arranging the computer means equipped with the drug administration program in the applicator, the optimum amount is automatically adjusted according to the drug at the optimum time. Can be administered.

[Simple explanation of drawings]

[Figure 1]

It is a figure explaining the principle of the transdermal drug applicator which concerns on this invention.

[Figure 2]

It is a cross-sectional view along the line 2-2 of FIG.

[Fig. 3]

It is a schematic diagram of the electric circuit incorporated in the transdermal drug applicator shown in FIGS. 1 and 2.

[Fig. 4]

It is another embodiment of the circuit shown in FIG.

[Fig. 5]

It is an enlarged sectional view of the Example of another display.

[Fig. 6]

It is an electrical schematic diagram of the circuit which carries out the 3rd ie feedback electrode and an applicator.

[Fig. 7]

It is a perspective view seen from the top of another drug applicator which carries out the electrodes isolated in a juxtaposed form.

[Fig. 8]

It is a partial cross-sectional view along the line 10-10 of Fig. 7.

[Fig. 9]

It is an electric schematic diagram which shows the circuit which carries out three active electrodes like the active electrode structure shown in FIG.

[Fig. 10]

It is an exploded perspective bottom view of the timer of the drug applicator and the mounting system.

[Fig. 11]

It is a perspective view of the timer and the attachment system shown in FIG. 10 attached to the patient's wrist.

[Fig. 12]

It is a diagram along lines 14-14 in Fig. 11.

[Fig. 13]

It is a diagram along lines 15-14 in Fig. 12.

[Fig. 14]

The outline of the embodiment shown in FIGS. 10 to 13 is an electric circuit.

[Fig. 15]

FIG. 3 is a perspective view of a watch body with a replaceable applicator with other refillable reservoirs shown by virtual lines.

[Explanation of symbols]

10 Applicator 12 outer cover 14 raised part 16 edge 18 skin 22 Semipermeable membrane 24 reservoir 26 contacts 28 battery 32 contacts 36 Adhesive layer 38 cells 50 LCD 60 indicator 61 layers 62 layers 63 Reservoir 64 gel 66 lead wire 67 lead wire