Patent Application
20190329033
The application relates to an electrotherapeutic device for inducing thrombosis and a use of the device in therapy of intracranial aneurysms. The application relates to a use of a stent releaser (e.g. a Solitaire stent releaser) and a Traxcess series guide wire (e.g. a Traxcess-14 guide wire) in electrothrombosis, particularly in treatment of aneurysms. The application also relates to a power source specifically for electrothrombosis.
The concept of “electrothrombosis” appeared as early as two centuries ago. Its principle is to form blood clots by attracting negatively charged blood cells, platelets, coagulation factors, etc. in blood using positive charges present on a surface of electrically conductive materials. In 1824, Scudamore discovered that an anode electrode produced a thrombus, while a cathode electrode did not, which opened the prelude to the study of electrical thrombosis. In 1847, Ciniselli induced thrombosis by using a direct current needle to puncture aneurysms, making this technique be applied in the study of aneurysm therapy for the first time.
However, with the progress of medical technologies and the continuous improvement of human health needs, limitations of electrothrombosis have been increasingly emerging. Mullan et al. performed angiography 6 months after the operation on 12 cases of intracranial aneurysms treated with electrothrombosis in 1965, and the results showed that the thrombosis induced by electrothrombosis could not last long but only played a temporary role, failing to reach a lasting aneurysm embolization effect. In 1969, Mullan further pointed out upon research that a part of electric thrombus in the initial intracranial aneurysms could not successfully embolize the aneurysm within a reasonable time, and even was more likely to cause aneurysm hemorrhage because it changed stable blood circulation in the aneurysms. It thus can be seen that the mere electrothrombosis often leads to a failure of the electrothrombosis treatment for the intracranial aneurysms due to the instability of a fresh thrombus and an immediately coming fibrinolysis process.
By 2004, HenkesH et al. obtained the conclusion that the principle of electrothrombosis plays a uncertain role in the embolotherapy of Guglialmi detachable coil intracranial aneurysms by studying surface thrombosis with a Guglialmi detachable coil. Since then, the idea of realizing aneurysm embolization with electrothrombosis has been gradually given up in the industry and, in turn, conventional intravascular therapy represented by simple mechanical filling was adopted. After that, the rapid development of various embolization techniques and auxiliary embolization stents has further established the dominance of coil embolization on the intracranial aneurysms.
Although the conventional embolization methods, represented by the coil embolization, have a definite effect in embolizing aneurysms and inducing thrombosis, many problems are often encountered in clinical practice, including but not limited to:
(1) the effects of conventional intravascular treatment methods on clinical microaneurysms (especially those in which microcatheters cannot enter tumor cavities) are often not ideal;
(2) for blood blister-like aneurysms, the effects with the conventional intravascular embolotherapy are not ideal, the costs for a dense mesh stent and the like are too high, and the requirements on path vascular conditions are high;
(3) for large aneurysms, residual tumor necks are often encountered by conventional embolization, it is difficult to achieve dense embolization, even assisted by a stent, and a relapse often occurs quickly; the dense mesh stent is feasible, but expensive; and
(4) for smoky intra-group aneurysms and arteriovenous malformations (AVM) intra-group aneurysms, it is often difficult to keep peripheral small blood supply arteries in a conventional intravascular therapeutic process, resulting in insufficient blood supply for patients after operation.
To sum up, up to now, there is still a need for an effective, convenient and lasting thrombus induction method in the industry for aneurysms that are difficult to be treated with the traditional interventional therapy methods, so as to bring better therapy for patients with such aneurysms.
For aneurysms that are difficult to be treated with traditional interventional therapy methods, while other people in the industry are looking for other new therapeutic approaches, the inventors of the application unexpectedly started with and improved electrothrombosis which has already been abandoned, seeking out an effective method for electrothrombosis, and have made an unexpected combinations by using materials originally used for other purposes in the art, thus designing a device for the method above. The method and the device not only can well form a thrombus, but also are simple, convenient and easy to implement, can make the effect of thrombus lasting, and well solve the problems existing in the background art mentioned above.
In one aspect, the application relates to a method for thrombosis, including the following steps of:
a step of performing electrothrombosis, wherein constant-current direct current within a certain range is applied to attract negatively charged factors such as leukocytes, platelets, coagulation factors and the like in blood to induce thrombosis; and
In another aspect, the application relates to a device for the implementation of the above-mentioned method. As shown in
The method and the device of the application are convenient in material choosing, and simple and easy to implement. Since there is no stimulation from mechanical filling, the sizes of blood clots can be increased, thereby reducing factors causing rebleeding during and after an intravascular therapy operation on ruptured aneurysms. Particularly, the method and the device of the application limit a microcatheter or a micro guide wire within the aneurysm, thus reducing risks and difficulties brought by complicated operation caused by a tortuous vascular path and insufficient supporting force.
In addition, a thrombus is further induced to be denatured and organized on the basis of thrombosis, which prevents a process of fiber dissolution, and the thrombus is stabilized so as to reduce the probability of secondary rupture and hemorrhage of the ruptured aneurysms in the near future. At the same time, the method and the device of the application save a large amount of cost, and are especially important for patients in economically underdeveloped areas.
The application can either utilize a specialized power source and guide wire, or a Solitaire stent releaser and a Traxcess-14 guide wire which are common in the market as the power source and the guide wire respectively. Although the original uses of the Solitaire stent releaser and the Traxcess-14 guide wire have nothing to do with electrothrombosis, the applicant unexpectedly discovered that a combination of the two can achieve the purpose of electrothrombosis very well. The application in another aspect relates to a use of a stent releaser (e.g., a Solitaire stent releaser), a Traxcess series guide wire (e.g., a Traxcess-14 guide wire), and a combination thereof in manufacturing a device for electric thrombosis.
In addition, in another embodiment, the applicant designs a constant current power source which is specially used as a power supply device for the electrothrombosis of the application. The power source is specifically designed based on the resistance of a human body and the current required by the electrothrombosis, and there is no such power source in the prior art that can output the current required by the electrothrombosis even after being connected with the human body like the power source designed by the application.
As mentioned above, a device of the application includes (or consists of) a power source and a guide wire portion.
The power source can be a commercially available constant current power source or constant voltage power source. The applicant discovered in clinical practice that the constant current power source has more advantages than the constant voltage power source as follows: although the constant voltage power source can provide constant output voltage, the stability and controllable output of current will be affected due to the individual differences in human body resistance of each person which cannot maintain stability at all times, while the constant current power source can directly provide constant current, which is more conducive to the stability of external conditions for thrombosis and the controllability of heat.
In a specific embodiment, the output current of the power source is about 0.1-50 mA, 0.2-20 mA, 0.5-10 mA or 0.8-5 mA. In another specific embodiment, the output current of the power source is about 0.8 mA, 1 mA, 1.5 mA, 2 mA, 3 mA, or 5 mA.
The applicant also surprisingly discovered that a commercially available stent releaser, such as a Solitaire stent releaser, can be used as a power source for the application. The stent releaser mainly uses the electrolysis principle in stent releasing, which has no relation with thrombosis in general medical practice. However, the inventors of the application unexpectedly discovered that the stent releaser can be advantageous in the electric thrombosis method of the application due to its stable and safe voltage (e.g., about 9 V), especially relatively constant current (e.g., about 0.8-1.0 mA) in the process of being power-supplied. Therefore, the application in another aspect relates to a use of a stent releaser (e.g., a Solitaire stent releaser) in electrothrombosis therapy and a use of the same in manufacturing a device for thrombosis.
In addition to using the stent releaser as a “guest” power source, other suitable power sources can also be used. For example, the inventors of the application design a power source which includes the following components: an internal power source, a voltage stabilizer, a diode, a first resistor, a second resistor, a third resistor, a first rheostat, an ammeter, an external electrode and a second rheostat, wherein the internal power source forms a power supply portion; the voltage stabilizer, the diode, the first resistor, the second resistor and the third resistor form a current control portion; the first rheostat and the second rheostat form a regulating portion; and the ammeter and the external electrode form an output portion. The regulating portion optionally further includes a position converter to switch the current between different switching positions, thereby constantly outputting corresponding current. Considering that subcutaneous resistance of a human body is generally not more than 500Ω, the resistance ranges of the various resistors and rheostats can be determined as follows.
In the power supply portion, the internal power source can directly adopt a direct current power source or form a direct current power source by converting external alternating current into direct current. Direct current output voltage of the power source may be about 10 V, 2 V, 14 V, 16 V, 18 V, 20 V, 22 V, 24 V, 26 V, 28 V, 30 V, 32 V, 34 V, 36 V, 38 V or 40 V, for example, a 24 V direct current power source is used.
In the current control portion, the voltage stabilizer is configured to ensure that a circuit voltage of the output portion is relatively stable. The voltage stabilizer can adopt a common three-terminal voltage stabilizer in the market, for example, an LM117HVH three-terminal voltage stabilizer. An output terminal of the voltage stabilizer is divided into two branches which are respectively connected with the first resistor for voltage division and the third resistor for current limiting. The reason why the third resistor for current limiting needs to be provided is that the resistance values of different living bodies vary greatly, which may also lead to excessive current variation. Therefore, it is necessary to provide the resistor for current limiting here for safety. A resistance value of the first resistor may be about 200 Ω, 220 Ω, 230 Ω, 250 Ω, 280 Ω, 300 Ω, 320 Ω, 30 Ω, 350 Ω, 380Ω or 400Ω. A resistance value of the third resistor may be about 500Ω, 1000Ω, 1500Ω, 2000Ω, 2500Ω, 3000Ω, 3500Ω or 4000Ω.
In addition, the diode is connected to a third terminal of the voltage stabilizer and connected with the second resistor in series, thereby protecting the voltage stabilizer from being damaged due to excessively high output voltage. Specifically, when the output terminal of the voltage stabilizer is connected with a large capacitor and an input terminal thereof has a small voltage holding capacity, a situation that the potential of the output terminal is higher than that of the input terminal will occur after power off, therefore, the diode needs to be arranged to allow the capacitor at the output terminal of the voltage stabilizer to discharge to the input terminal so as to protect the voltage stabilizer. One or more (e.g., one, two or three) diodes may be connected in series according to the need for current regulation. A resistance value of the second resistor may be about 5 Ω, 10 Ω, 15 Ω, 20 Ω, 25 Ω, 30 Ω, 35 Ω, 40Ω.
In the regulating portion, the first rheostat is connected with the third resistor in series; the first rheostat and the third resistor together are connected with the second rheostat in parallel; and the first rheostat is configured to regulate current in a large range between different living bodies (for example, between different patients). The maximum resistance value of the first rheostat may be about 5 kΩ, 5.5 kΩ, 6 kΩ, 6.5 kΩ, 7 kΩ, 7.5 kΩ, 8 kΩ, 8.5 kΩ, 9 kΩ, 9.5 kΩ, 10 kΩ, 10.5 kΩ, 11 kΩ, 11.5 kΩ, 12 kΩ, 12.5 kΩ, 13 kΩ, 13.5 kΩ, 14 kΩ, 14.5 kΩ, or 15 kΩ. The first rheostat may be provided with several (for example, three) switching positions, and the resistance values of the switching positions may be about 0.5 kΩ, 1 kΩ, 1.5 kΩ, 2 kΩ, 2.5 kΩ, 3 kΩ, 3.5 kΩ, 4 kΩ, 4.5 kΩ, 5 kΩ, 5.5 kΩ, 6 kΩ, 6.5 kΩ, 7 kΩ, 7.5 kΩ, 8 kΩ, 8.5 kΩ, 9 kΩ, 9.5 kΩ, 10 kΩ, 10.5 kΩ, 11 kΩ, 11.5 kΩ, 12 kΩ, 12.5 kΩ, 13 kΩ, 13.5 kΩ, 14 kΩ, 14.5 kΩ, and 15 kΩ.
The second rheostat is configured to fine-tune the current when the living body fluctuates in a small range (for example, when operating on the same patient). The maximum resistance value of the second rheostat may be about 10 kΩ, 11 kΩ, 12 kΩ, 13 kΩ, 14 kΩ, 15 kΩ, 16 kΩ, 17 kΩ, 18 kΩ, 19 kΩ, 20 kΩ, 21 kΩ, 22 kΩ, 23 kΩ, 24 kΩ, 25 kΩ, 26 kΩ, 27 kΩ, 28 kΩ, 29 kΩ, or 30 kΩ. The second rheostat may also be provided with several (for example, three) switching positions, and the resistance values of the switching positions may be about 1 kΩ, 2 kΩ, 3 kΩ, 4 kΩ, 5 kΩ, 6 kΩ, 7 kΩ, 8 kΩ, 9 kΩ, 10 kΩ, 11 kΩ, 12 kΩ, 13 kΩ, 14 kΩ, 15 kΩ, 16 kΩ, 17 kΩ, 18 kΩ, 19 kΩ, 20 kΩ, 21 kΩ, 22 kΩ, 23 kΩ, 24 kΩ, 25 kΩ, 26 kΩ, 27 kΩ, 28 kΩ, 29 kΩ or 30 kΩ.
The regulating portion may also include the position converter connected with the first rheostat and the third resistor in series, and the function of current switching is realized by switching a control switch to different switching positions. The number of the switching positions may be two, three, four or five, etc. each of the switching positions is connected with a certain resistor so as to adjust the current within the range of the above-mentioned output current; and the resistance value of the resistor is related to the third resistor and the first rheostat, as well as to the resistance of different living bodies. For example, the resistance value of the resistor connected to each switching position can be about 0 kΩ, 0.3 kΩ, 0.5 kΩ, 1 kΩ, 2 kΩ, 3 kΩ, 4 kΩ, 5 kΩ, 6 kΩ, 7 kΩ, 8 kΩ, 9 kΩ, 10 kΩ, 11 kΩ, 12 kΩ, 13 kΩ, 14 kΩ, 15 kΩ, 16 kΩ, 17 kΩ, 18 kΩ, 19 kΩ, 20 kΩ, 21 kΩ, 22 kΩ, 23 kΩ, 24 kΩ, 25 kΩ, 26 kΩ, 27 kΩ, 28 kΩ, 29 kΩ or 30 kΩ respectively so as to control the output current at about 0.5 mA, 1 mA, 1.5 mA, 2 mA, 2.5 mA, 3 mA, 3.5 mA, 4 mA, 4.5 mA or 5 mA.
In the output portion, the ammeter is an ammeter commonly used in the industry, which is configured to indicate the current in electrothrombosis operation, and may act as a portion of the panels 6 described above. The measuring range of the ammeter matches the common current range of electrothrombosis, such as being 0-5 mA, 0-10 mA, 0-20 mA or 0-50 mA, etc. When in use, the first rheostat and/or the second rheostat can be regulated according to the readings of the ammeter. The external electrode corresponds to the above-mentioned anode 3 and cathode 5. The ammeter and the external electrode are connected with the first rheostat and the third resistor in series.
For the above-mention power source,
In addition, the output guide wire of the application can adopt a guide wire commonly used in clinic. Preferably, the guide wire is provided with a head end with good conductivity, moderate heat generation and electrolytic resistance.
The inventors of the application unexpectedly discovered that commercially available Traxcess series guide wires, such as a Traxcess-14 guide wire, are very suitable for use as an output guide wire of the application. The Traxcess guide wire was originally only used for general intravascular diagnosis or treatment by cooperating with a microcatheter, and there were no reports of its use in thrombosis. Due to its good conductivity and strong electrolytic resistance (e.g., the proximal of the Traxcess-14 guide wire has an insulating coating over 140 cm except for about 3 cm at the tail end, which is beneficial to the concentration of positive charge to the head end covered by an inert platinum coil), the Traxcess guide wire is adapted to be used as the guide wire being charged with electricity in the method for electrothrombosis of the application. Therefore, the application in another aspect relates to a use of the Traxcess guide wire, especially the Traxcess-14 guide wire, in electrothrombosis therapy and to a use in manufacturing a device for thrombosis.
The output guide wire of the application (for example, at the head end) is optionally equipped with a device for measuring a temperature or for temperature alarm, and/or an auxiliary device for introducing a microcatheter.
The input guide wire used in the application can be a guide wire commonly used in clinic, for example, a wire provided on an electrode of a common medical power source or a stent releaser can be used as the input guide wire. The input guide wire can be connected with a metal syringe needle and pricked under the skin of a human body (for example, under the skin of a thigh), or be tied at an appropriate position on the human body, or be pasted on the skin through a patch, thereby realizing circuit communication with the human body and forming a loop. Under the condition of not being pricked under the skin, one should pay attention to the fact that the resistance value of the human body will become larger. In order to ensure proper current, the parameters of the power source, such as voltage and internal resistance, should be regulated accordingly.
The application also relates to a use of a combination of a Solitaire stent releaser and a Traxcess-14 guide wire in electrothrombosis therapy and a use in manufacturing a device for thrombosis.
The following cases treated with the method and device of the application are aneurysms which are difficult to treat by conventional treatment methods, and the immediate postoperative effect and reexamination effect are very ideal.
Materials and Method
A commercially available Traxcess-14 guide wire is used as an output guide wire, the tail end (namely, the conductive end without the coating) is connected to the anode of the Solitaire stent releaser, the head end of the guide wire is super-selected to an aneurysm cavity, and all guide wire portions inside of the body up to a tumor neck are isolated beyond the range of blood circulation by the microcatheter. In the thigh portion, a needle (a metal needle capable of conducting electricity, such as a common syringe needle) penetrates into the skin and is connected with a wire (serving as an input guide wire) on the cathode of the power source of the Solitaire stent releaser, so that positive charges converge at the aneurysm cavity, and current passes through a subcutaneous resistor of the human body and returns to the cathode of the release device via a thigh needle, thereby forming a complete loop (the principle is exactly the same as that of the release device).
During operative procedures, the head end of the guide wire is super-selected into the aneurysm cavity, the proximal end of the tumor neck is protected by the microcatheter in the whole process, the power source of the Solitaire stent releaser is powered on to realize the electrothrombosis operation in a intermittent way, and the current is controlled at about 1 mA when being powered on. Three times of such operation form one stage and one stage is followed by angiography until the effect is satisfactory.
Case Description
Case 1: a male who was 15 years old was injured after falling down when riding a motorcycle. He has multiple dissecting aneurysms and pseudoaneurysms at bilateral carotid arteries. With the above-mentioned operation, pseudoaneurysm to which the microcatheter cannot enter is subjected to eletrotherapy merely.
The therapeutic process is shown in
Case 2: a male who was 49 years old was admitted to hospital due to subarachnoid hemorrhage (SAH). As shown in the angiography in
Case 3: a female who was 51 years old had a headache and had vomited for 10 days. Head CT showed hematocele in a prepontine cistern, an annular cistern and a fourth ventricle, and Head CTA showed the presence of extremely small aneurysms of the basilar truncus artiriosus. The angiography of the aneurysms is shown in
The above-mentioned examples are only used to illustrate or explain the technical scheme of the application, and should not be construed as constituting any limitation to the application. Any improvement and modification of this application without creative labor shall also be deemed to fall within the scope of this application.
| Number | Date | Country | Kind |
|---|---|---|---|
| 201710053933.0 | Jan 2017 | CN | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/CN2018/073182 | 1/18/2018 | WO | 00 |
