SUBSTANCES

The invention relates to a device for delivering medication directly to a patient's brain and to the use of such a device.

In view of the limitation of existing central nervous system (CNS) delivery systems it is an object of the present invention to provide a method and device for enhanced and controlled multi administration of a biologically active substance or agent that allows for effective concentrations of said agent in tissues of the CNS by essentially

circumventing the systemic compartment and the blood-brain barrier.

Applying intra nasal agent delivery as described for instance in international patent application WO 2010123804 does not always yield the possibility to lead enough agents to the CNS system via the nasal cavity. It is also not possible to offer more than one agent at once or a large amount of agent or a certain amount of agent in a short time. Furthermore, it is known that agent delivery in the skin using ionthophoresis irritates or otherwise damages the skin so another agent has to be used as well to treat the irritation.

Therefore there is a need both to create the possibility to deliver more than one agent at once, or a larger amount of agent or a certain amount of agent in a shorter time than possible until now, and to vary the ways of delivery of said agents to prevent irritation without applying another agent to treat the irritation with its own side effects.

It is an object of the present invention to provide a device to be able to deliver more than one agent at once. It is a further object of the present invention to provide an amendment on the agent delivery as described above so that the irritation caused upon the use of this delivery system will decrease substantially, especially when it is used for a long time.

The present invention provides a device of the type stated in the preamble comprising: as active electrode(s) at least one iontophoresis wire which is optionally splitted, cooperable with a medication administration device, the iontophoresis wire being insertable into one or more of the six cavities selected from the ear, ocular and nasal ones with the proviso that not only in one or both nasal cavities one or more iontophoresis wires are placed, through which the medication will be delivered;

at least one passive electrode; and

a controller regulating an electric charge to the iontophoresis wire.

Preferably such a device of the invention comprises one splitted iontophoresis wire or more iontophoresis wires insertable into one or more of the six cavities selected from the ear, ocular and nasal ones with the proviso that not only in one or both nasal cavities one or more iontophoresis wires are placed. More preferably such devices comprise a delivery device for a cleaning solution in one or more cavities where a medication administration device is present, by either applying wires in said cavity or cavities and a controller regulating an electric charge or another type of energy to this wire, or by applying mechanical pressure, as for instance a spray. The cleaning solution is especially sodium chloride.

A particular embodiment according to the invention comprises an iontophoresis wire being insertable into one ear cavity and an iontophoresis wire being insertable into the other ear cavity or in the form of one common iontophoresis wire with split ends to both ear cavities.

The present invention further provides the use of a device according to the invention for delivering medication to the brain of a patient by

placing a medication administration tube and optionally a cleaning solution administration tube in one or more of the six cavities selected from the ear, ocular and nasal ones with the proviso that not only in one or both nasal cavities one or two tubes are placed,

through which the medication and optionally the cleaning solution will be delivered wherein an iontophoresis wire as active electrode is cooperable with the medication administration tube and

optionally another ionthophoresis wire is cooperable with the cleaning solution administration tube or the cleaning solution is delivered by applying a spray securing a passive electrode to the patient at another place spaced from the active electrode as for instance at the back side of the head

delivering the medication to the medication administration tube by regulating an electric charge to the iontophoresis wire cooperable with the medication administration tube optionally delivering a cleaning solution by either reversing the electric charge on the iontophoresis wire and regulating an electric charge to the iontophoresis wire cooperable with the cleaning solution administration tube or by applying a spray.

More particular, as part of this use the step of delivering a cleaning solution is carried out before or both before and after the step of delivering the medication.

Preferably, the device of the invention will (also) be used for delivering two or more medical agents to the brain of a patient by placing two or more medical agents administration tubes in two or more of the cavities selected from the ear, eyes and nose, with the proviso that not only in one or both nasal cavities one or two tubes are placed. The improvement of the agent delivery as described above consists in the application of one or more active electrodes and one passive electrode insertable into at least one ear cavity or one ocular cavity and optionally combined with one or more nasal or one or more ear or one or more ocular cavities. The passive electrode may be positioned on another place in the neighborhood of the active electrode or preferably on the back of the patient's head. In this way one or more active electrodes all applicable in cavities selected from the ear, nasal and ocular cavities are applied in the device and use according to the invention, with the proviso that at least one of the cavities applied is an ear or ocular cavity.

The agent will comprise a medication or biologically active agent which will be transported by iontophoresis or by another type of energy delivery or will comprise a cleaning solution as for instance sodium chloride, which will be transported by electrophoresis.

The invention will now be further elucidated with reference to seven embodiments and an associated figure. In the figure: figure 1 shows an embodiment with as active electrodes (1) two wires cooperable with an agent administration device applied in two ear cavities, with the passive electrode (2) placed on the back of the head, together with a controller (3). figure 2 shows an embodiment with as active electrode (1) one wire cooperable with an agent administration device applied in an ear cavity, with the passive electrode

(2) placed in the other ear cavity, together with a controller (3).

figure 3 shows an embodiment comparable to that shown in figure 1 , but then as active electrodes (1) one wire split in two ends, a further difference is that the passive electrode (2) has been placed on another part of the back of the head.

figure 4 shows an embodiment with as active electrodes (1) one wire split in two ends cooperable with an agent administration device applied in two ocular cavities, with the passive electrode (2) placed on the back of the head, together with a controller

(3) .

figure 5 shows an embodiment with as active electrodes (1) one wire split in two ends, each again split in two ends cooperable with an agent administration device, each end applied in one ear and one nasal cavity of the same half of the head, with the passive electrode (2) placed on the back of the head, together with a controller (3). figure 6 shows an embodiment with as active electrodes (1) one wire split in three ends cooperable with an agent administration device applied in one ear, one ocular and one nasal cavity of the same half of the head, with the passive electrode (2) placed on the back of the head, together with a controller (3).

figure 7 shows an embodiment with as active electrodes (1) two wires each split in three ends cooperable with an agent administration device applied in one ear, one ocular and one nasal cavity of the same half of the head, with the passive electrode (2) placed on the back of the head, together with a controller (3).

The figures are predominantly schematic and not drawn to scale. Corresponding parts are designated in the figures with the same reference numerals. Figure 1 shows in detail a front and side view of a head whereupon one device according to the invention has been applied. Two wires have been applied as two active electrodes (1) in both ear cavities, the passive electrode (2) on the back of the head, in general dependent on the exact place where the medical agent has to be delivered. As shown in figure 2, the passive electrode can be applied in one of the ear, ocular and nasal cavities as well, also dependent on the exact place where the medical agent has to be delivered. As in figure 3 has been shown: also wires split into more parts may be used as active electrodes. In the figures 4 - 7 more possibilities of applying active electrodes on one or more of the ear, ocular and nasal cavities have been shown.

In one embodiment as active electrode a wire cooperable with an agent administration device is applied in one nasal cavity and as active electrode a similar wire in one ear canal or one wire with split ends to both active electrodes, together with a controller regulating an electric charge to the wire. In figure 5 a comparable embodiment has been shown, but then with the application of a wire split in two wires which both have again been split in two wires making a total of four wires. Each of the two wires resulting from the second split are applied both in the same half of the head, in this embodiment in the ear and nasal cavity.

The controller (3) applied in the device of the invention shown in each figure is regulating an electric charge or another type of energy to the wire. Generally, the agent to be transported to the cerebral part of the head will comprise a medication which will be transported for instance by iontophoresis or a cleaning solution comprising for instance sodium chloride, which will be transported for instance by electrophoresis. A further aspect of the present invention provides the possibility to provide more than one agent at once by applying in both ears an active electrode and one passive electrode somewhere else as for instance in one of the nasal cavities or on the back of a patient's head, as depicted in figure 1. If desired, one of the wires and electrodes may be used to pass on music.

The term ionthophoresis as used in the present patent application includes without any limitation such terms as electrophoresis, electrotransport, iontokinesis, electroosmosis, and any combination of the same. Furthermore, the terms catheter and tube have been used interchangeably, the same is valid for the terms substance and agent. Finally, if in the present patent application the use of one or more of the ear and ocular and nasal cavities has been mentioned it should be realized that the device with the use of one or two of the nasal cavities alone has been excluded.

The electrode functions as the pathway for the delivery of agents, transfer of ionthophoretic energy, and a cleaning solution before and after treatment. According to an even further aspect of the invention it will be possible to provide up to six agents at once by applying active electrodes in as much cavities as suitable out of two nasal cavities, two ears and two ocular cavities together with a passive electrode as for instance depicted in figure 7.

Preferably, a plastic or other neutral catheter or tube is inserted into for instance the ear or nasal or ocular cavity, as deep as possible but without pain. In this catheter two smaller catheters or tubes are inserted. The first small catheter delivers the agents to treat the brain. Through the second one neutral solutions or neutral compositions in another form which will neutralize the treatment agent, which was delivered prior to the brain through the first catheter, will be delivered. As neutral solution for instance sodium chloride, NaCl is used, which solution will clean the tissue in the ear or nasal or ocular cavity after the agents have been delivered. This is done because after the delivery of the agents and ionthophoresis the intra ear or ocular or nasal tissue can be irritated. In the plastic tube there will also be a very small cord, which will go to the end of the plastic catheter or tube in the ear or ocular or nasal cavity. The outside portion of the cord will be connected to a controller regulating the charge.

The further improvement consists in the delivery of a cleaning solution to one or more of the ear or ocular or nasal cavities after, before or both before and after treatment, to reduce irritation or other damage to the tissue or the respective cavities and around these cavities from the ionthophoretic process or the agent being used. Preferably, the cleaning solution is not administered by iontophoresis but by applying mechanical pressure as for instance by a spray. lonthophoresis occurs through a wire which is insertable into each ear or ocular or nasal cavity as has been described in the international patent application WO 2010123804 which content has to be considered to be included completely in the present patent application. Instead of more than one wire splitting of a wire to more electrodes may be applied. A controlling system regulates the electric charge through the wire of lonthophoresis, the delivering cleaning substances and other parameters are also controlled. When it is needed to deliver agents to the brain for a long period of time, it is preferred to use a battery as delivery of charge to the electrodes at both sides of the wire, inserted in ear or nasal or ocular cavity. This enables people to administer the agents into the brain themselves at any given point in time it is needed.

Both the active and passive electrodes will be connected to the controller regulating the charge as well as a programmed computer. The program will arrange the changing of the poles, the duration of delivery, and the kilovolts applied to the device, etc. In case two wires of two active electrodes are applied to two of each ear and nasal and ocular cavity, the first small catheter will be connected to a vial of agents under large pressure. The other small catheter will be connected to a vial of neutral or other agents, which will also be under large pressure.

According to another specific embodiment the first small catheter, the end which is inserted in the ear or ocular or nasal cavity, will have a piece of cotton, wool, or likewise material, so that when the agent is delivered it will go into the cotton or other material used. The electric charge will then push the agent from the material into the cerebral part of the brain.

As described in WO 2010123804 as well, another way of preventing irritation of the tissue may be achieved by programming the poles on the electrodes of the

lonthophoresis device programmed to an automatical change. For example, the negative electrode fixed in the ear or ocular or nose cavity will be changed to positive and the other electrode, which is fixed at the back of the head, will become negative. This change, for some minutes, will remove the irritation of the tissue in the ear cavity. In this way one can use the agent delivery route via the ear cavity to the central nervous system (CNS) and treat chronic diseases for a long time.

These devices and procedures will prevent irritation or other damages in one or more of the ear and ocular and nasal cavities using specially delivered agents to clean the tissue after or before, or both after and before ionthophoresis is applied and to change the polarity, time, power and other elements of the procedure. This will allow one to use agent delivery through one or more of the ear and ocular and nasal cavities to the brain for a long time, as well as for many months and years.

A unique treatment of patients with many kinds of brain illnesses or the improvement of the brain of healthy people has been provided, which is achieved using

ionthophoresis with the administration of medication.

When the illnesses have reached the spinal cord, for example if a patient has Multiple Sclerosis, the second electrode (passive) is fixed on the vertebral column on the first or second lumbar part of the column or on another level of the vertebral column. In this situation, the patient should be placed in either a vertical position or in a sitting position, which will help the agent from the brain to reach the spinal cord.

It is known that the nervous system regulates the functions of the body as for example all internal organs, such as the heart, the gastrointestinal, the liver, etc. as well as muscles and the intellectual functions of a human being. Therefore, the delivery of agents or agents to prevent diseases will prolong life and improve the healthiness of many people, by not only treating those who are ill, but preventing these illnesses to occur in the future, thus making life longer.

For chronic diseases one must administer agents every day, sometimes two or three times a day, for several hours or the whole day long, during the duration of several months and years. For example, these chronic conditions include Alzheimer's disease, Parkinson's, cancer, and other diseases that have to be treated for many years.

Furthermore, if for instance a patient is using electrodes in both of his ears then it is obvious that the patient will not have a direct connection to his immediate external environment, causing him not to hear what is being said for the entire duration of the treatment. Therefore, preferably one small plastic tube which is completely empty should be inserted into the electrode without any wires providing the patient music during his long treatment at his desire. However, he could always remove the music device from his ear, so as to hear what is being said by people in his immediate external environment. In this way a patient with a chronic disease is able to continue oral communication with his immediate external environment although he is ill.

Although the invention has been elucidated above with reference to several

embodiments and uses thereof, it will be apparent that the invention is by no means limited thereto. On the contrary, many other variations are possible within the scope of the invention for the person with ordinary skill in the art.