WO2023027652A1

WO2023027652A1 - System for realizing the treatment of diseases and disorders via invasive stimulation of the nerves

Info

Publication number: WO2023027652A1
Application number: PCT/TR2021/050978
Authority: WO
Inventors: Ali Can ERK; Ali Veysel OZDEN
Original assignee: Vagustim Saglik Teknolojileri Anonim Sirketi
Priority date: 2021-08-26
Filing date: 2021-09-24
Publication date: 2023-03-02

Abstract

The invention relates to a system, which allows the auricular vagus nerve to be invasively stimulated for 24 hours in order to treat the diseases and/or disorders. More particularly, the invention relates to a system, which enables the invasive stimulation of the auricular vagus nerve via the electric signals sent by at least one microstimulator and/or at least one nanogenerator positioned under the skin.

Description

SYSTEM FOR REALIZING THE TREATMENT OF DISEASES AND DISORDERS VIA INVASIVE STIMULATION OF THE NERVES

Subject of the Invention

The invention relates to a system, which allows the auricular vagus nerve to be invasively stimulated for 24 hours in order to treat the diseases and/or disorders.

State of the Art

The autonomic nervous system is a system controlling all of the vital functions of the body. In other words, all of the functions of our organs that are not able to be controlled by ourselves are managed by the autonomic nervous system. The activity of the autonomic nervous system varies during the daily life, serving to enable our body to accommodate the changes in the internal and external environment. The impairments in the variable activity of the autonomic nervous system lead to the impairment in the body's ability to adapt to the variables in the internal and external environment, resulting in the emergence of the autonomic dysfunction and the associated diseases. Activation of the nerves via stimulation is employed for the treatment of the resulting disorders and diseases.

The nerves may be stimulated by sending electric signals to various nerves via various sections. The stimulation for the treatment of different disorders is realized via different sections of different nerves by using the signals with different electrical characteristics. The properties of the stimulation signal to be sent, the duration of stimulation and the periods of stimulation differ according to the disorder intended to be treated. The treatment of some diseases such as epilepsy requires uninterrupted stimulation for the duration of 24 hours. Carrying out the stimulation noninvasively or minimally invasively brings about some difficulties. The fact that the stimulation of the nerve in question for 24 hours is performed via a stimulator positioned on the skin leads to the discomfort and causes problems especially in the children and in the individuals with mental inabilities. In the studies according to the state of the art conducted for realizing the invasive stimulation of the vagus nerve, the stimulation is carried out via the cervical area and in a unilateral manner. The vagus nerve is the 10^th cranial nerve and the most important component of the parasympathetic nervous system. Although the mechanism of action for the vagus nerve stimulation is still not well understood, it is believed to affect the cerebral blood flow and neural activity through the afferent fibers. Since the invasive vagus stimulation affects the efferent fibers also via the cervical area, it is possible to perform the stimulation unilaterally, and in this case, the risk for side effects is greater compared to the afferent stimulations, besides the surgical complications. Hoarseness, sore throat/dysphagia, coughing and labored breathing are among the most frequently encountered side effects of the invasive cervical stimulation (Ohemeng KK, Parham K. Vagal Nerve Stimulation: Indications, Implantation, and Outcomes. Otolaryngol Clin North Am. 2020 Feb; 53(1):127-143).

A great deal of studies has shown that the transcutaneous vagus nerve stimulation (tVNS) could be able to elicit therapeutic effects similar to those generated by the equivalent invasive vagus nerve stimulation. tVNS is a noninvasive technique, which involves the application of electric currents by means of surface electrodes at certain locations and which most commonly targets the auricular branch of the vagus nerve (ABVN) and the cervical branch of the vagus nerve in the neck. Currently, there is no material evidence for the most suitable location for tVNS or for the stimulation parameters providing the greatest therapeutic effects for a certain location (Yap JYY, Keatch C, Lambert E, Woods W, Stoddart PR, Kameneva T. Critical Review of Transcutaneous Vagus Nerve Stimulation: Challenges for Translation to Clinical Practice. Front Neurosci. 2020 Apr 28; 14:284). In light of the up-to-date data, interior of concha and tragus may be regarded as the suitable locations for the auricular vagal modulation (Butt MF, Albusoda A, Farmer AD, Aziz Q. The anatomical basis for transcutaneous auricular vagus nerve stimulation. J Anat. 2020 Apr; 236(4):588-611). tVNS is safe and has been well tolerated at the doses tested in the research studies until the present (Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018 Nov-Dec; 11(6):1225-1238). However, a stimulation lasting 24 hours may be required for some diseases such as epilepsy. Further, the noninvasive stimulation may not be possible in the pediatric age group or in the patients with mental retardation. Despite its disadvantages, the invasive stimulation may be a preferable method in such cases. The auricular vagus nerve stimulation may be performed in a minimally invasive manner via the percutaneous method (Kampusch S, Kaniusas E, Szeles JC. Modulation of Muscle Tone and Sympathovagal Balance in Cervical Dystonia Using Percutaneous Stimulation of the Auricular Vagus Nerve. Artif Organs. 2015 Oct; 39(10):E202-12). However, no study regarding the stimulation of the auricular vagus nerve in an entirely invasive manner as in the cervical area is encountered in the literature.

Within the scope of the invention, a system, which is able to stimulate the auricular vagus nerve invasively for 24 hours by means of at least one microstimulator and/or at least one nanogenerator without leading to any discomfort in the user, is developed.

Object of the Invention

An object of the invention is to develop a system whereby the treatment of diseases and/or disorders is enabled via the electrical stimulation of the auricular vagus nerve.

Another object of the invention is to develop a system whereby the treatment of diseases and/or disorders is enabled via the invasive electrical stimulation of the auricular vagus nerve.

Another object of the invention is to develop a system whereby the invasive electrical stimulation of the auricular vagus nerve is realized by means of at least one microstimulator and/or at least one nanogenerator, said system allowing the stimulation for 24 hours without leading to any discomfort in the user.

Description of the Figures

Figure 1: A view showing the auricular section of the vagus nerve Reference Numerals

A : Section where the auricular vagus nerve is located

K : Ear

KT : Skull

Description of the Invention

In a preferred embodiment of the invention, the microstimulators and/or nanogenerators that provide the stimulation are positioned in the body subcutaneously.

The vagus nerve has a branch also behind the ear (K), at the joint of ear (K) and the skull (KT) (Amandeep Singh, BS Tuli, Isha Preet Tuli, Navneet Kaur Tuli. Textbook of Ear, Nose and Throat (2013); Watanabe K, Tubbs RS, Satoh S, Zomorodi AR, Liedtke W, Labidi M, Friedman AH, Fukushima T. Isolated Deep Ear Canal Pain: Possible Role of Auricular Branch of Vagus Nerve-Case Illustrations with Cadaveric Correlation. World Neurosurg. 2016 Dec; 96:293-301). In a preferred embodiment of the invention, the microstimulator and/or nanogenerator is/are positioned subcutaneously in said area behind the ear (K).

In a preferred embodiment of the invention, the vagus nerve behind the ear (K) is stimulated by means of said microstimulators and/or nanogenerators. The vagus nerve has fibers also on the back side of earlap of the ear (K), just at the location where the earlap adjoins the skull (KT). The microstimulator and/or nanogenerator contained in the system according to the invention is/are a microstimulator and/or nanogenerator that is/are to anatomically fit this area and to be positioned under the skin. By means of the system according to the invention, this area is stimulated by the microcurrents with strength not perceivable by the individual. The section behind the ear (K), at the joint of ear (K) and the skull (KT) where the branch of the vagus nerve is located; i.e. the section where the auricular vagus nerve is located (A); i.e. the section where the electrodes and/or the microstimulator and/or nanogenerator is/are to be positioned, is shown in Figure 1.

In another preferred embodiment, the stimulation is transmitted to the tragus and/or concha sections of the ear (K) along with the vagus nerve behind the ear (K) or only to the tragus and/or concha sections of the ear (K) without stimulating the vagus nerve behind the ear (K).

In a preferred embodiment of the invention, said microstimulator and/or nanogenerator has/have a cylindrical form factor. Further, in a preferred embodiment of the invention, at least one of said microstimulators and/or nanogenerators preferably has a diameter in the range of 0.5-30 mm and a height/length in the range of 0.5-40 mm.

In a preferred embodiment of the invention, the electronic components of the system according to the invention are disposed within a glass cage suitable for being positioned in the body. The electrodes to provide the electrical conduction are the iridium electrodes, which would be able to be positioned in a circular arrangement on at least one end, preferably on each end, of said cage, said cage preferably having a cylindrical form.

In a preferred embodiment of the invention, the system according to the invention is positioned only behind the left ear (K) or only behind the right ear (K). In another preferred embodiment of the invention, the system is positioned behind both ears (K). In case of the system being positioned behind both ears (K), it is possible to control the devices separately or together.

The invention comprises at least one power storage unit for supplying power to the stimulator. Said power storage unit is preferably positioned into said cage. In a preferred embodiment of the invention, said power storage unit may be charged in a non-contact manner. Still, in a preferred embodiment of the invention, the power storage unit is charged by the stimulator depending on the body movements.

In a preferred embodiment of the invention, a battery, which is not chargeable but has a long service life, is used as the power storage unit.

In a preferred embodiment of the invention, the settings for the system according to the invention are performed and said system is then positioned under the skin. In another preferred embodiment of the invention, it is possible to establish wireless communication with the system according to the invention and it is possible to perform the settings wirelessly also following the placement of the system under the skin. It is possible to set the current parameters and adjust other system settings by establishing communication with the system according to the invention via smart devices by the use of Bluetooth or similar wireless methods.

Owing to the system according to the invention, it is made possible to invasively stimulate the auricular vagus nerve for 24 hours for the purpose of treatment of diseases and disorders.

Claims

1. A system for realizing the treatment of diseases and disorders via the invasive stimulation of the auricular vagus nerve characterized in that it comprises at least one microstimulator and/or at least one nanogenerator positioned under the skin and generating the electric signals sent for the stimulation of the nerves.

2. A system according to Claim 1 characterized in that it comprises at least one electrode, which enables the transmission of the electric signals generated by at least one microstimulator and/or at least one nanogenerator.

3. A system according to Claim 2 characterized in that at least one electrode, which enables the transmission of the electric signals, is an iridium electrode.

4. A system according to Claim 2 or 3 characterized in that said at least one electrode is an electrode positioned subcutaneously in the body.

5. A system according to any one of Claims 2-4 characterized in that said electrode is an electrode positioned in the branch of the vagus nerve that is located behind the ear (K), at the joint of the ear (K) and the skull (KT).

6. A system according to Claim 4 or 5 characterized in that said electrode is an electrode positioned subcutaneously in the branch of the vagus nerve that is located behind the ear (K), at the joint of the ear (K) and the skull (KT).

7. A system according to any one of the preceding claims characterized in that said at least one microstimulator and/or at least one nanogenerator is/are a microstimulator and/or nanogenerator positioned subcutaneously in the body.

8. A system according to any one of the preceding claims characterized in that at least one microstimulator and/or at least one nanogenerator is/are a microstimulator

7 and/or nanogenerator positioned in the branch of the vagus nerve that is located behind the ear (K), at the joint of the ear (K) and the skull (KT).

9. A system according to Claim 7 or 8 characterized in that at least one microstimulator and/or at least one nanogenerator is/are a microstimulator and/or nanogenerator positioned subcutaneously in the branch of the vagus nerve that is located behind the ear (K), at the joint of the ear (K) and the skull (KT).

10. A system according to Claim 8 or 9 characterized in that at least one microstimulator and/or at least one nanogenerator is/are a microstimulator and/or nanogenerator having a structure anatomically fitting the area behind the ear (K), at the joint of the ear (K) and the skull (KT), where the branch of the vagus nerve is located.

11. A system according to any one of Claims 5-10 characterized in that it is a system where the stimulations are transmitted also to the tragus and/or concha sections of the ear (K) along with the auricular vagus nerve behind the ear (K).

12. A system according to any one of Claims 5-10 characterized in that it is a system where the stimulations are transmitted only to the tragus and/or concha sections of the ear (K), without the auricular vagus nerve behind the ear (K) being stimulated.

13. A system according to any one of the preceding claims characterized in that the diameter of at least one microstimulator and/or at least one nanogenerator is 0.5 - 30 mm.

14. A system according to any one of the preceding claims characterized in that the height/length of at least one microstimulator and/or at least one nanogenerator is 0.5 - 40 mm.

15. A system according to any one of the preceding claims characterized in that it comprises at least one glass cage in which at least one microstimulator and/or nanogenerator is disposed for being positioned in the body.

8 A system according to Claim 15 characterized in that said glass cage is a glass cage with a cylindrical form. A system according to any one of Claims 2-6 or 15-16 characterized in that said glass cage is a glass cage, on at least one end of which at least one electrode is positioned. A system according to Claim 17 characterized in that said glass cage is a glass cage, on each end of which at least one electrode is positioned. A system according to Claim 17 or 18 characterized in that the cage is a cage, on the ends of which the electrodes are positioned in a circular manner. A system according to any one of Claims 5-19 characterized in that it is a system where at least one microstimulator and/or at least one nanogenerator and/or at least one electrode is/are positioned behind the right ear (K). A system according to any one of Claims 5-19 characterized in that it is a system where at least one microstimulator and/or at least one nanogenerator and/or at least one electrode is/are positioned behind the left ear (K). A system according to any one of Claims 5-19 characterized in that it is a system where at least one microstimulator and/or at least one nanogenerator and/or at least one electrode is/are positioned behind the right ear (K) and at least one microstimulator and/or at least one nanogenerator and/or at least one electrode is/are positioned behind the left ear (K). A system according to Claim 22 characterized in that at least one microstimulator and/or at least one nanogenerator and/or at least one electrode behind the right ear (K) and behind the left ear (K) is/are a microstimulator and/or nanogenerator and/or electrode able to be controlled simultaneously or independently of one another.

24. A system according to any one of the preceding claims characterized in that it comprises at least one power storage unit supplying power to the system.

25. A system according to Claim 15 or 16 or 24 characterized in that said power storage unit is positioned into the glass cage.

26. A system according to Claim 24 or 25 characterized in that said power storage unit is a power storage unit that is chargeable.

27. A system according to Claim 26 characterized in that said power storage unit is a power storage unit that is able to be charged wirelessly.

28. A system according to Claim 26 or 27 characterized in that said power storage unit is a power storage that is charged by the stimulator depending on the body movements.

29. A system according to any one of the preceding claims characterized in that it is a system with which the wireless communication may be established after being placed under the skin.

30. A system according to Claim 29 characterized in that it is a system where the current parameters and the other system settings may be adjusted in a wireless manner after said system is positioned under the skin.