WO2021248895A1

WO2021248895A1 - Animal vagus nerve stimulation system and manufacturing method therefor

Info

Publication number: WO2021248895A1
Application number: PCT/CN2020/141951
Authority: WO
Inventors: 许扶; 郭剑
Original assignee: 北京品驰医疗设备有限公司
Priority date: 2020-06-10
Filing date: 2020-12-31
Publication date: 2021-12-16
Also published as: CN111729191B; CN111729191A

Abstract

Disclosed are an animal vagus nerve stimulation system and a manufacturing method therefor. The system comprises a protective tube (110) formed by a flexible cylindrical plastic tube having an axial opening (113), with a surgical suture (111) being provided on two sides of the axial opening (113) thereof, such that the axial opening (113) of the protective tube (110) can be pulled open by means of pulling the surgical sutures (111) to the two sides, and after the surgical sutures are released, the axial opening (113) of the protective tube (110) returns to the original state; two stimulation contacts (120), which are hollow semi-annular-shaped metal parts, with the inner ring coming into contact with the vagus nerve (200), and the outer ring being attached and fixed to the inner wall of the protective tube (110); and two coated wires (130), one end of each wire extending to the hollow positions of the stimulation contacts (120) and being connected to the stimulation contacts (120), and the other ends thereof radially protruding out of the inner wall of the protective tube (110) at the axial middle position, with the protruding ends being connected to a plug connector (140).

Description

Animal vagus nerve stimulation system and manufacturing method thereof

Technical field

The invention belongs to the technical field of medical instrument manufacturing, and specifically relates to an animal vagus nerve stimulation system and a manufacturing method thereof.

Background technique

Epilepsy is a neurological disease in which the sudden abnormal discharge of brain neurons leads to transient brain dysfunction. The disease has a high disability rate, long course and recurring attacks, which seriously threatens the physical and mental health of patients. Vagus Nerve Stimulation (Vagus Nerve Stimulation) fixes electrodes on the vagus nerve and continuously stimulates the nerves to cause changes in brain electrical activity and neurotransmitters to achieve the purpose of treating epilepsy. This therapy is non-destructive, reversible and adjustable, and has become one of the important surgical methods for the treatment of epilepsy.

The mechanism of vagus nerve stimulation is the synergy or balance of many factors, including changes in cerebral blood flow in the brain, functional connections of EEG, or depletion and blocking of neurotransmitters, etc. At present, the actual mechanism of action of vagus nerve stimulation by domestic and foreign medical researchers is not clear. Involving the particularity of the human brain and ethics and other reasons, medical researchers mostly use animals as research objects (rats, mice, rabbits, monkeys, etc.), using animal experiments to simulate the stimulation process and study the treatment of vagus nerve electrical stimulation The mechanism of action, thereby improving the effect of nerve stimulation, and can be expanded to new targets and new indications in the future.

The patents of CN103638596A and CN203647859U have disclosed electrodes for stimulating the vagus nerve in animals, but the solder joint structure in the electrodes needs to be protected and insulated in a separate plastic tube, which increases the size and weight of the electrode, and causes the electrode to affect mice. It is not suitable for small animals, and the electrodes are difficult to operate during surgical implantation, and the reliability after implantation is poor.

Summary of the invention

In view of the above problems, the present invention provides an animal vagus nerve stimulation system and a manufacturing method thereof.

In one aspect, the present invention provides an animal vagus nerve stimulation system comprising a stimulator, a stimulation electrode, wherein: the stimulation electrode comprises a protective tube, at least two stimulation contacts, at least two coated wires;

The protective tube is a flexible insulating tube that opens in the axial direction;

The stimulation contact is a hollow half-ring shaped metal piece, the inner ring is in contact with the vagus nerve, and the outer ring is fixed on the inner wall of the protective tube;

Each of the coated wires corresponds to one of the stimulation contacts. One end penetrates into the hollow position of the stimulation contact and is connected to the stimulation contact, and the other end is passed out of the protective tube and directly Or indirectly connected to the stimulator. Further, there is a surgical suture on each side of the axial opening of the protective tube, and pulling the surgical suture to both sides can pull the axial opening of the protective tube to loosen the surgical suture. After the threading, the axial opening of the protective tube is restored to its original shape.

Further, the normal direction of the center of the inner ring arc of the stimulation contact point all faces the axial opening position of the protection tube.

Further, the coated wire is indirectly connected to the extracorporeal stimulator through the connector, or directly connected to the intracorporeal stimulator.

Further, the coated wire is connected to the connector or the internal stimulator by welding or crimping.

Further, the stimulator includes a circuit board and a protective casing; the circuit board can output electrical signals of different frequencies, pulse widths and amplitudes; the protective casing is outside the circuit board and can connect the circuit board with External isolation plays a role of electrical insulation.

Further, a colored marking strip is provided at a position adjacent to one of the stimulation contacts outside the protective tube to distinguish the positive and negative electrodes of the electrode.

Further, the outer diameter of the protective tube is 0.5mm-2mm, the inner diameter is 0.4mm-1.8mm, and the length is 3mm-8mm; the diameter of the inner ring of the stimulation contact is 0.1mm-1mm, and the diameter of the outer ring is the same as that of the The inner diameter of the protective tube is the same, the length is 0.3mm-2mm, and the distance between two adjacent stimulation contacts is 1mm-5mm.

Further, the material of the protective tube is silica gel, polyurethane or polyurethane-silicone rubber copolymer; the material of the stimulation contact is platinum or platinum-iridium alloy; the material of the wire in the coated wire is stainless steel, cobalt-chromium-molybdenum alloy , Nitinol or platinum-iridium alloy.

On the other hand, the present invention provides a method for manufacturing an animal vagus nerve stimulation system, which includes the steps of: S1, welding the coated wire to the hollow position of the stimulation contact;

S2: Fix the outer ring of the stimulation contact on the inner wall of the protective tube with a bio-glue to ensure that the center of the arc of the inner ring of the stimulation contact faces the axial opening position of the protective tube;

S3: Pass the other end of the coated wire from the inner wall of the protective tube in a radial direction, and connect it directly or indirectly to the stimulator.

The animal vagus nerve stimulation system in the present invention has a simple structure and small size, and can be used for vagus nerve stimulation of small animals, such as mice, rats, and the like. The system of the present invention has a short production cycle, simple implantation operation, high reliability, and can be implanted in an animal body for a long time and provides stable electrical stimulation.

Description of the drawings

Figure 1 is a schematic diagram of an animal vagus nerve stimulation system provided by a first embodiment of the present invention;

Figure 2 is a schematic diagram of an animal vagus nerve stimulation system provided by a second embodiment of the present invention;

Figures 3(a) to 3(d) are schematic diagrams of the implantation process of the animal vagus nerve stimulation system of the present invention.

Explanation of labels in the figure: 110-protection tube, 111-surgical suture, 112-marker tape, 113-axial opening, 120-stimulation contact, 130-coated wire, 140-plug, 141-protective glue , 150-in vivo stimulator, 151-circuit board, 152-protective shell, 200-animal vagus nerve, 300-surgical non-absorbable suture

detailed description

In the following, the present invention will be described in detail through embodiments with reference to the accompanying drawings.

FIG. 1 is a schematic diagram of an animal vagus nerve stimulation system provided by the first embodiment of the present invention. The animal vagus nerve stimulation system includes an animal vagus nerve stimulation electrode, a connector 140, a protective glue 141 and an external stimulator (not shown). Among them, the animal vagus nerve stimulation electrode includes a protective tube 110, two stimulation contacts 120, and two coated wires 130.

The protective tube 110 is a flexible cylindrical plastic tube with an opening 113 along the axial direction, and there is a surgical suture 111 on each side of the opening. Pulling the two surgical sutures 111 to both sides can pull off the axial opening 113 of the protective tube. After the surgical suture 111 is loosened, the axial opening of the protective tube 110 can be restored to its original shape. The outer diameter of the protective tube 110 is 0.5-2 mm, preferably 1.3 mm; the length is 3-8 mm, preferably 5 mm in length. The material of the protection tube 110 is silica gel, polyurethane or polyurethane-silicone rubber copolymer, which has an insulating effect.

The two stimulation contacts 120 are hollow half-ring shaped metal pieces. The material is platinum or platinum-iridium alloy. The diameter of the inner ring of the stimulation contact 120 is 0.1-1mm, preferably 0.4mm, the diameter of the outer ring is the same as the inner diameter of the protective tube 110, and the diameter of the outer ring is the same as the inner diameter of the protective tube. The inner diameter of the protective tube 110 is 0.4mm-1.8mm, preferably It is 0.9mm. The distance between the two stimulation contacts 120 is 1-5 mm, preferably 3 mm; the length of the two stimulation contacts 120 is 0.3 mm-2 mm, preferably 0.5 mm. The inner ring of the stimulation contact 120 is in contact with the vagus nerve 200, and the outer ring is attached and fixed to the inner wall of the protective tube 110. The axes of the two stimulation contacts 120 coincide with the axis of the protection tube 110, and the center normal of the inner ring arc faces the axial opening position of the protection tube 110. The hollow structure of the stimulation contact 120 can accommodate the coated wire 130.

The electrode has two coated wires 130. One end of the two coated wires 130 penetrates into the hollow position of the stimulation contact 120 and welded together, and the other end is passed through the inner wall of the protective tube 110 at the axial middle position and radially out of the inner wall. The penetrated end is welded to the corresponding connector 140. The wire material is stainless steel wire, cobalt-chromium-molybdenum alloy wire, nickel-titanium alloy wire, platinum-iridium alloy wire, etc., which can be in the form of stranded wire or spiral wire to improve the overall fatigue resistance of the electrode.

The connector 140 is used to connect an extracorporeal stimulator (not shown). The connector 140 can be a micro usb male and female connector, a DuPont connector, a terminal block, an alligator clip, and the like. The exposed pins and solder joints of the connector 140 are covered by a protective glue 141 to provide electrical insulation. The material of the protective glue 141 can be silicon rubber, polyurethane, or epoxy resin.

There is a colored marking strip 112 at the position adjacent to the contact on one side of the protective tube 110, which is used to distinguish the positive and negative poles of the electrode, so as to facilitate the determination of the electrode implantation direction during the operation.

2 is a schematic diagram of an animal vagus nerve stimulation system provided by a second embodiment of the present invention. The animal vagus nerve stimulation system includes an animal vagus nerve stimulation electrode and an integrated internal stimulator 150. Among them, the animal vagus nerve stimulation electrode includes a protective tube 110, two stimulation contacts 120, and two coated wires 130. In this embodiment, the coated wire 130 is directly connected to the internal stimulator 150. In this embodiment, the features of other parts of the electrode are the same as those of the first embodiment.

The extracorporeal stimulator or intracorporeal stimulator 150 includes a circuit board 151 and a protective housing 152. The circuit board 151 can output electrical signals with a fixed frequency, pulse width, and amplitude. In the above-mentioned first embodiment, the connector 140 is connected to the extracorporeal stimulator; in the second embodiment, the end of the coated wire 130 passing through the protective tube is welded to the circuit board 151. The protective casing 152 is outside the circuit board 151, and can isolate the circuit board 151 from the outside, thereby playing a role of electrical insulation. As in the second embodiment, the circuit

board

151 and the bodily fluid isolated. The material of the protective shell 152 is silicon rubber, polyurethane, epoxy resin and the like.

The present invention also proposes a method for manufacturing the animal vagus nervous system: laser welding the coated wire 130 to the hollow position of the contact 120, and then fix the outer ring of the contact 120 to the inner wall of the protective tube 110 with bio-glue to ensure the contact The center direction of the inner circle arc of the point 120 all faces the axial opening position of the protection tube 110. The other end of the coated wire 130 is penetrated from the axial middle position of the protective tube 110 in the radial direction, and is welded or crimped together with the connector 140. The exposed parts of the pins of the connector and the solder joints are covered with protective glue 141 to ensure mutual insulation between the positive and negative electrodes. The extracorporeal stimulator is detachably connected to the connector 140. In the absence of the connector 140, the other end of the coated wire 130 is connected to the internal stimulator 150, and the coated wire 130 is directly welded or crimped to the internal stimulator 150. This connection method is not detachable.

Fig. 3 is a schematic diagram of the implantation process of the animal vagus nerve stimulation system of the present invention. The implantation method of the stimulation system is as follows: Step 1, after the animal is anesthetized, make a midline incision in the neck to expose the left side carotid artery sheath, and separate the vagus nerve trunk about 1 cm; Step 2, as shown by the arrow in Figure 3(a) Pull the surgical suture 111 of the electrode protection tube 110 in the direction of the finger to open the axial opening 113. The state after the axial opening 113 of the electrode is opened is shown in Figure 3(b), the inner ring of the two stimulation contacts 120 Exposed. In the third step, the vagus nerve 200 is placed in the protective tube 110 and is in contact with the inner ring of the stimulation contact 120, as shown in Figure 3(c). In the fourth step, the surgical suture 111 is loosened, the protective tube 110 returns to its original shape, and it is confirmed that the protective tube 110 completely covers the vagus nerve 200. Then use two surgical non-absorbent sutures 300 to tie the two contact points 120 outside the protective tube 110 to fix the position of the electrode on the vagus nerve 200, as shown in Figure 3(d). Finally, the connector 140 is subcutaneously sneaked to the neck of the rat, and the connector is fixed to the animal's skull with dental cement. After the connector 140 is connected to the extracorporeal stimulator, the electrical signal can be transmitted to the vagus nerve of the animal. If the coated wire 130 is directly connected to the internal stimulator 150, the internal stimulator 150 can be placed and fixed under the skin of the animal's back or abdomen.

This embodiment is only a preferred embodiment of the present invention, but the protection scope of the present invention is not limited to this. Any person skilled in the art can easily think of changes or substitutions within the technical scope disclosed by the present invention. , Should be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.

Claims

An animal vagus nerve stimulation system, comprising a stimulator and a stimulation electrode, wherein: the stimulation electrode includes a protective tube, at least two stimulation contacts, and at least two coated wires;

It is characterized in that, the protective tube is a flexible insulating tube that opens in the axial direction;

The stimulation contact is a hollow half-ring shaped metal piece, the inner ring is in contact with the vagus nerve, and the outer ring is fixed on the inner wall of the protective tube;

Each of the coated wires corresponds to one of the stimulation contacts. One end penetrates into the hollow position of the stimulation contact and is connected to the stimulation contact, and the other end is passed out of the protective tube and directly Or indirectly connected to the stimulator.
The animal vagus nerve stimulation system according to claim 1, characterized in that: there is a surgical suture on both sides of the axial opening of the protective tube, and pulling the surgical suture to both sides can be The axial opening of the protective tube is pulled open, and after the surgical suture is loosened, the axial opening of the protective tube returns to its original shape.
The animal vagus nerve stimulation system according to claim 1, wherein the center normal of the inner circular arc of the stimulation contact points all toward the axial opening position of the protective tube.
The animal vagus nerve stimulation system according to claim 1, wherein the coated wire is indirectly connected to an external stimulator through a connector, or directly connected to an internal stimulator.
The animal vagus nerve stimulation system according to claim 4, wherein the coated wire is connected to the connector or the internal stimulator by welding or crimping.
The animal vagus nerve stimulation system according to claim 5, characterized in that: the stimulator comprises a circuit board and a protective housing; the circuit board can output electrical signals of different frequencies, pulse widths and amplitudes; the protection The casing is outside the circuit board, which can isolate the circuit board from the outside and play a role of electrical insulation.
The animal vagus nerve stimulation system according to claim 1, characterized in that: outside the protective tube near one of the stimulation contacts, a colored marking strip is provided for distinguishing the positive and negative electrodes of the electrodes. .
The animal vagus nerve stimulation system according to claim 1, wherein the outer diameter of the protective tube is 0.5mm-2mm, the inner diameter is 0.4mm-1.8mm, and the length is 3mm-8mm; the stimulation contact The diameter of the inner ring is 0.1mm-1mm, the diameter of the outer ring is the same as the inner diameter of the protective tube, the length is 0.3mm-2mm, and the distance between two adjacent stimulation contacts is 1mm-5mm.
The animal vagus nerve stimulation system according to claim 1, wherein:

The material of the protective tube is silica gel, polyurethane or polyurethane-silicone rubber copolymer;

The material of the stimulation contact is platinum or platinum-iridium alloy;

The material of the wire in the coated wire is stainless steel, cobalt-chromium-molybdenum alloy, nickel-titanium alloy or platinum-iridium alloy.
The manufacturing method of an animal vagus nerve stimulation system according to any one of claims 1-9, characterized in that:

S1, welding the coated wire to the hollow position of the stimulation contact;

S2: Fix the outer ring of the stimulation contact on the inner wall of the protective tube with a bio-glue to ensure that the center of the arc of the inner ring of the stimulation contact faces the axial opening position of the protective tube;

S3: Pass the other end of the coated wire from the inner wall of the protective tube in a radial direction, and connect it directly or indirectly to the stimulator.