WO2012102415A1 - Electroactive polymer oscillator, method for manufacturing same, and method for dissolving blood clots using same - Google Patents

Abstract

The present invention relates to an electroactive polymer oscillator for dissolving blood clots, comprising: a pillar-shaped electroactive polymer laminate; a plurality of electrode coating layers disposed on a portion of the surface of the pillar-shaped laminate; and a capsule layer for encapsulating the electrode coating layers. The electroactive polymer oscillator in accordance with the present invention can be used in a small blood vessel such as a cerebral blood vessel, can minimize the generation of side effects such as blood vessel damage, can be used while injecting medicine, can minimize the amount of a blood clot-dissolving agent that is administrated to decrease the danger of bleeding due to drugs, can maximize the dissolving efficiency of the blood clot, and can ensure biosafety by means of encapsulating the oscillator using a material having biocompatibility with respect to blood and which is stable in vivo. Using a method for pulverizing blood clots by inserting an active catheter including the electroactive polymer oscillator according to the present invention, and by applying a current to oscillate the polymer oscillator, a combination of mechanical and medical effects can be obtained to increase the permeation of drugs into the blood clot.

Description

 【Specification】

 [Name of invention]

 Electro-Active Polymer Oscillator, Manufacturing Method thereof and Thrombolysis Method Using the Same

 The present invention relates to an electroactive polymer vibrator, and more particularly, to an ionic polymer-metal complex capable of responding to high frequency, minimizing side effects such as vascular damage, reducing the risk of bleeding caused by drugs, and thrombolytic efficiency. It relates to a thrombolytic electroactive polymer vibrator for maximizing and a method for manufacturing the same and a thrombolytic method using the same.

 Background Art

 <2> Stroke is the single most common cause of death among Koreans (1st statistical data), accounting for 15.1% of all deaths. Korea has the highest mortality rate from cerebrovascular disease among the 0ECD countries. In particular, the incidence of ischemic stroke has increased rapidly recently, with an average annual rate of 7.9%.

 <3> Since stroke is very important for the rapid treatment after stroke, there is an urgent need for a treatment method that can be universally applied at local medical institutions. Intraperitoneal thrombectomy (IA thrombolysis) is a commonly used treatment for 3–6 hours of onset. Conventional thrombolysis by topical intraarterial drug administration is a method of placing a microcatheter on an arterial blockage caused by a thrombus, and injecting a thrombolytic agent (tPA, Urokinase) into the artery to dissolve the thrombus and attempt to revascularize. There is a problem in that the thrombolytic effect of the drug is limited and the risk of cerebral hemorrhage caused by the drug is increased.

 <4> mechanical thrombectomy for successful reopening of blood vessels

(mechnical thrombectomy) has been devised, and many instruments have been developed for this purpose, but the success rate is low, there are technical difficulties in use, and there are problems of vascular damage and bleeding due to intravascular manipulation of the instrument. In addition, for the rapid reopening of blocked blood vessels, limited mechanical comminution may be applied during drug infusion, and wire and stent black may attempt to partially comminute thrombi using balloon conduits. There are many problems.

<5> In order to increase the dosing effect of thrombolytics, a method of applying ultrasonic waves to the site of thrombi was devised. However, when ultrasonic waves are applied outside the body, the efficiency is low. Problems such as damage occur, and the lack of flexibility of the instrument is not suitable for application to cerebrovascular vessels. <6> Applying physical vibration (ll, 000 Hz) to thrombus improves thrombolytic rate (US patent, 5,498,236, 1996). Mechanical vibration device complicates the mechanical part and does not apply to cerebrovascular due to lack of flexibility of mechanical part. It is not possible to use materials such as piezo elements (PZT), shape memory alloys (SMA), etc., which are designed as substitutes, but they are difficult to miniaturize, lack flexibility, and are difficult to satisfy the driving force and displacement for thrombolysis. There is an urgent need for the development of new materials that can be applied in small blood vessels such as cerebrovascular vessels. In particular, the driving material proposed for the development of medical devices is mostly SMA, but since it is driven by heat transfer, it has low efficiency and weak fatigue stiffness. There are a lot of limitations in the use of medical devices such as causing damage to the body.

On the other hand, a driving body using an electroactive polymer uses an electrical stimulus, which is relatively controlled, and has an advantage of being relatively small in size and light, and the electroactive polymer is transformed into Maxwell force appearing when a voltage is applied. Modified polymer, conductive polymer deformed by ion transfer, Ionic polymer-metal composite (IPMC), etc. Among the electroactive polymer materials, IPMC has excellent flexibility, processability, energy efficiency and biocompatibility. Therefore, there is an advantage in biomedical and biomimetic use, and recently, the possibility of use in biomedical fields such as bio-miniature robots, therapeutic micro tips, drug carriers, artificial surgical materials, etc. has been actively proposed.

 However, there are many problems such as fabrication of micro-driven bodies and reproducibility of driving performance, so that the electroactive polymer material suitable for actual use has not yet been realized, and especially for the development of blood-only medical devices and medical active catheters. Attempts to develop active polymer actuators and vibrators are still insufficient worldwide.

 In addition, attempts have been made to use electroactive polymer actuators for medical artificial muscles and small robots and to manufacture them as medical active catheters, but no attempt has been made to use them for the purpose of thrombus removal.

 [Detailed Description of the Invention]

 [Technical problem]

 Accordingly, the first problem to be solved by the present invention is to provide a thrombolytic electroactive polymer vibrator that can minimize vascular damage and maximize thrombolytic efficiency.

The second problem to be solved by the present invention is to provide a method for manufacturing the electroactive polymer vibrator. A third object of the present invention is to provide an active catheter capable of injecting the electroactive polymer vibrator and thrombolytic agent, and a thrombolytic method using the same.

 A fourth problem to be solved by the present invention is a method for evaluating driving characteristics and a method for adjusting factors affecting driving characteristics and a thrombus that can optimize the performance of the electroactive polymer vibrator for effective thrombolysis. In evaluating an electrolytic polymer vibrator having excellent solubility, it is to provide an excellent thrombolytic electroactive polymer vibrator screening method using the factors of driving force, driving displacement, and response speed of the electroactive polymer vibrator.

 Technical Solution

 In order to achieve the first object of the present invention,

 <15> (i) a columnar electroactive polymer laminate, (Π) a plurality of electrode coating layers present on a portion of the surface of the columnar laminate, and () a capsule for encapsulating the polymer laminate and the electrode coating layer. It provides an electroactive polymer vibrator comprising a coating layer.

According to an embodiment of the present invention, the electroactive polymer is selected from silver polymer, conductive polymer, carbon nanotube, dielectric polymer, electrostrictive polymer, nano clay, silica compound and combinations thereof Can be.

According to one embodiment of the present invention, the ionic polymer is a fluorine-based polymer in which at least one ion group selected from sulfonic acid group and carbonyl group is introduced, and the fluorine-based polymer is one or two or more selected from May be a combination.

-CF2CF)-{CF2CF; ₂ ) *-, (CH2CF2)-(QF2CF)-

O-CF2CF (CF; ₃ ) -0-CF2G! F2 G _3- (GHaCFa)-

<18>,,

According to an embodiment of the present invention, the conductive polymer may be selected from polyaniline, polypyri, polysulfone, polyacetylene, and combinations thereof.

 According to an embodiment of the present invention, the dielectric polymer may be selected from polyacrylate, silicon, polyvinylidene fluoride, and combination thereof.

According to one embodiment of the present invention, the electroforming polymer may be selected from polyacrylate, silicone, polyurethane, and combinations thereof. According to an embodiment of the present invention, the nanoclay may be introduced with at least one ion group selected from a sulfonated group and a carbonyl group.

 According to one embodiment of the present invention, the silica compound may be selected from silica monomers modified through sulfonation or carbonylation and combinations thereof.

 According to an embodiment of the present invention, the electrode may be selected from platinum, gold, copper, silver, nickel lead, cadmium, and alloys thereof.

 According to an embodiment of the present invention, the capsular coating layer is made of paraline N (Di-para-

Xylylene), paraline C (Di-Chloro-para-Xylylene), paraline D (Tetra-Chloro-Para- ᅳ Xylylene) and combinations thereof.

 According to an embodiment of the present invention, the plurality of electrode coating layers are continuously or intermittently positioned in the longitudinal direction of the lamp stack, and are evenly spaced so as to be opposed to the surface of the planar or curved surface of the column stack. And a gap exists between the plurality of electrode coating layers and is insulated.

According to one embodiment of the present invention, the electroactive polymer vibrator is a single layer or two or more mixed layers selected from conductive polymers, carbon nano-lubes and transition metal oxides between the lamp stack and the electrode coating layer. And at least one layer selected from silicon-based, epoxy-based, parylene-based, and polyurethane-based coating layers present on the electrode coating layer and the insulating layer.

According to an embodiment of the present invention, the electroactive polymer vibrator has a cross-section of 0.6X

0.6-1.0X1.0 隱² , length 5-15 瞧, driving force 0.5-3.0 g _f , driving displacement

40-90 ^° , characterized in that it responds with a stepping speed of 1.0-1.5 瞧 / s at 1-20 Hz.

 In order to achieve the second object of the present invention,

(A) laminating a plurality of electroactive polymer ion exchange membranes, (b) heating the laminated ion exchange membrane at 170-190 ^° C. for 10-20 minutes, and (c) the heated Thermally compressing the ion exchange membrane at 6,500-7,000 psi and 170-190 ^° C. for 10-20 minutes; (d) cutting the thermally compressed ion exchange membrane to obtain a columnar laminate; A method of manufacturing an electroactive polymer vibrator, the method comprising: coating an electrode on a surface of the columnar laminate, and (f) forming an insulating layer by partially removing the electrode coating layer.

In order to achieve the third object of the present invention, A catheter comprising the electroactive polymer vibrator, having a spherical force of 0.5-3.0 g _f or more, a drive displacement of 40-90 ^°, an intensity of 8xiO ^_7 Nnf or more, a density of less than 0.25 g / oi and a density of less than 2.0 mW / _s . It is characterized in that the diameter of less than 1.5 mm and the catheter is used as an active catheter for the electroactive polymer vibrator and the thrombolytic injection of the catheter.

 In the thrombolysis method, the catheter is inserted into a thrombus and an electric current is applied to vibrate the polymer vibrator to pulverize the thrombus, and at the same time, a thrombolytic agent is introduced through the catheter to dissolve the thrombus, and then the dissolved thrombus It provides a thrombolytic method, characterized in that the suction (suction).

 In addition, by evaluating the driving characteristics selected from the driving force, the driving displacement and the stepping speed of the electroactive polymer vibrator for effective thrombosis, the type of the ion group, mobility of the eungi and oscillator so that the driving characteristics are optimized for thrombolysis. It provides a method for adjusting a factor selected from the voltage applied to.

 In addition, in evaluating an electroactive polymer vibrator having excellent thrombolytic properties, an excellent thrombolytic electroactive polymer vibrator screening method using the factors of driving force, driving displacement, and response speed of the electroactive polymer vibrator is described. provided

^ C.

^: - favorable effects;

 The electroactive polymer vibrator according to the present invention is an ionic polymer-metal complex capable of responding to high frequencies, and has a driving characteristic suitable for thrombolytic dissolution. It can be applied to, side effects such as vascular damage can be minimized, can be used in parallel with drug injection, and the dose of thrombolytic agent can be minimized, reducing the risk of bleeding caused by drugs and maximizing thrombolytic efficiency. In addition, the vibrator can be encapsulated in a blood compatibility and in vivo stable material to ensure biosafety. In addition, a method of pulverizing a blood clot by inserting it into a blood clot using an active catheter including an electroactive polymer vibrator according to the present invention and applying a current to vibrate the polymer vibrator may inject a drug into the blood clot simultaneously with a mechanical effect. There is a combined effect of increasing.

 [Brief Description of Drawings]

1 is a schematic diagram showing the driving principle of an electroactive polymer vibrator, an ionic polymer-metal composite (IPMC), a Nafion ion exchange membrane, and an IPMC according to an embodiment of the present invention. It is also.

 Figure 2 is a schematic diagram showing the production by the thermal lamination method using the thermal properties in the production of the ion exchange membrane according to an embodiment of the present invention.

3 is a schematic diagram of a method of forming an electrode through a chemical reduction method on the surface of an ion exchange membrane prepared according to an embodiment of the present invention and a photograph of the formed electrode.

4 is a photograph showing a shape of a 2 × 1 mrf cross-sectional electroactive polymer vibrator and a driving performance graph according to an embodiment of the present invention.

Figure 5 is a graph measuring the driving force different from Hz for the electro-active polymer vibrator according to an embodiment of the present invention.

 6 is a schematic view showing a thrombolytic method according to the present invention.

 [Form for implementation of invention]

 Hereinafter, the present invention will be described in more detail.

 The present invention relates to an electroactive polymer including an electrically conductive polymer laminate, a plurality of electrode coating layers present on a part of the surface of the lamp laminate, and a calsul coating layer encapsulating the polymer laminate and the electrode coating layer. It is characterized by being a vibrator.

 The present invention is characterized in that it is an IPMC (ionic polymer-metal composite) drive for the manufacture of an electroactive polymer vibrator that is sensitive to low voltage, high HZ. IPMC is characterized in that the bending deformation due to the volume change due to the movement of the ion-solvent in the ion exchange membrane when the voltage is applied.

The electroactive polymers forming the shaped laminates may be selected from ionic polymers, conductive polymers, carbon nanotubes, dielectric polymers, electrostrictive polymers, nanoclays, silica compounds, and combinations thereof. Can be used.

 In the present invention, the 'combination' includes all of the two or more copolymers or molten phases, or liquid blends, the molten or liquid or solid mixtures of the two or more substances, and combinations thereof. .

Specifically, the ionic polymer is a fluorine-based polymer into which at least one ionic group selected from a phonic acid group and a carbonyl group is introduced, and as the fluorine-based polymer, for example

-(GH ^ CF

One or two or more combinations selected from the art can be used, and as an example, the sulfonic acid group is introduced as an anion group.

Nafion containing among the fluorine-based polymers can be used. Specifically, the conductive polymer may be selected from fulyaniline, polypyri, polysulfone, polyacetylene, and combinations thereof. The dielectric polymer may be selected from polyacrylate, silicon, polyvinylidene fluoride, and combinations thereof. The selected one may be used, and the electromodified polymer may be selected from polyacrylate, silicone, polyurethane, and combinations thereof, and the nano clay may be one in which one or more ionic groups selected from sulfonated and carbonyl groups are introduced. have.

 Introduction of ionic groups of the nanoclay is generally used in the art, and is not particularly limited. For example, the present invention uses a method of controlling the amount of ionic groups by irradiating gamma rays, but is not limited thereto. The silica compound may use silica monomers modified through sulfonation or carbonylation and combinations thereof. In the present invention, it is known that the conductive polymer, carbon nanotube, dielectric polymer, electrostrictive polymer, nanoclay, silica compound, etc. used as the electroactive polymer cause the volume change by various physical and chemical changes. The driving performance is improved by the volume change.

In the present invention, in the case of using two or more kinds of electroactive polymers in combination, in particular, in the case of combining the ionic polymer and the carbon nanotubes, they are mixed in solution to prepare a membrane in the range of 175-185 // in. By laminating this, an electroactive polymer vibrator may be manufactured, or a polymer vibrator is manufactured from one electroactive polymer, and then a method of coating another species of electroactive polymer on the surface of the prepared polymer vibrator may be used. In this case, a method of preparing a membrane using a solution phase mixture may be a three-dimensional constant casting method, which is generally used in the art. If the coating is not particularly limited, for example, a method of impregnation and coprecipitation in a polymer solution and then polymerization on the surface is also possible. <5i> The lamp-shaped laminate may be prepared by thermally compressing an electroactive polymer having a thickness of 175 to 185 mm 3 to have a final thickness of 700 to 1100. If the final thickness of the electroactive polymer is less than 700, it may be difficult to use the catheter vibrator due to the reduction of the driving force.If the final thickness of the electroactive polymer is greater than 1100, the driving speed and displacement are significantly reduced due to the increase of its rigidity. This may cause a problem that cannot be inserted into the vessel.

 The electrode coating layer formed by coating the surface of the lampshade laminate is used in the art, but is not particularly limited. Specifically, one selected from platinum, gold, copper, nickel, lead, cadmium, and alloys thereof may be used. In the present invention, platinum is used as a metal for forming the electrode coating layer. However, even when the electrode is formed using nickel, lead, copper, or silver or the electrode is formed using gold, the present invention is not limited to platinum. Does not.

 The electrode coating layer is present on a part of the surface of the light emitting stack, and is continuously or intermittently positioned in the longitudinal direction of the light stack, and is even in number so as to correspond to the surface of the flat or curved surface facing the light stack. There is a gap between the plurality of electrode coating layers and is insulated. By producing electrodes intermittently in the longitudinal direction and adjusting the applied voltage to each electrode, deformation of various shapes such as an S shape can be generated to greatly improve the flexibility of the driving unit.

 The electroactive polymer vibrator of the present invention may further include a single layer or two or more mixed layers selected from conductive polymers, carbon nanotubes, and transition metal oxides between the lamp stack and the electrode coating layer. . The conductive polymer, carbon nanotubes, transition metal oxide and inorganic particles are not particularly limited to those commonly used in the art, specifically, the conductive polymer is selected from polyaniline, polypy, polysulfone and polyacetylene. Mixtures of more than one species may be used, and the transition metal oxide may be an oxide of a transition metal such as vanadium. These additional layers are formed using ¾ coating, layer-by-layer self-assembly, spin coating, atomic layer deposition, sputtering, electropolymerization and chemical polymerization, which are commonly used in the art, and affect the driving performance. Take into account the 10-200 thickness range.

 In addition, paraline on the electrode coating layer to ensure biocompatibility and blood compatibility

It may further comprise a capsule coating layer consisting of N (Di-para-Xylylene), Paraline C (Di-Chloro- para-Xylylene), Paraline D (Tetra- Chloro-Para-Xylylene), and combinations thereof. have. This layer is present not only on the electrode layer but also on the gaps between the electrode layers which serve as insulating layers. The coating layer can secure the biocompatibility and blood compatibility by improving the blocking force between the polymer vibrator and the external tissue inside.

The coating layer also forms a coating layer by using dip coating, thermal evaporation, and thermal curing, which are generally used in the art, and maintains a 1-3 βm thickness range in consideration of the effect on driving performance.

The electroactive polymer vibrator according to the present invention has a cross section of 0.6X0.6-1.0X1.0 kHz ', a length of 5-15 kHz, a driving force of 0.5-3.0 g _f , and a driving displacement of 40-90 °. It is characterized by humping at 1-20 Hz.

To <58> The transducer according to the present invention is applied to the fibrinolytic preferably has a maximum cross-sectional area of 0.8X0.8画² below. However, in order to confirm the characteristics of the vibrator, an embodiment of the present invention manufactured a vibrator having a cross-sectional area of 2 × 1 nrf and evaluated its characteristics. The vibrator according to the present invention was confirmed to be a material exhibiting excellent driving force of 1 gf or more, which can be sensed at 10 Hz.

 Figure 4 shows the shape and driving performance of the 2X1 mrf cross-sectional vibrator according to the present invention. a) is width, b) is thickness, c) and d) is the actual measured thickness and width, e) the sensitivity at 1, 5 and 10 Hz, and f) is the driving force.

 In addition, the driving force was measured at different Hz, and the result is shown in FIG. 5 in comparison with the number of vibrations per minute. When more than 300 movements per minute were applied with a driving force of 0.3 gf or more, it was confirmed that the optimal condition for thrombolysis.

 <6i> A method of manufacturing an electroactive polymer vibrator according to the present invention includes the steps of (a) laminating a plurality of electroactive polymer ion exchange membranes, and (b) the stacked ion exchange membranes at 10-20 at 170-190 ° C. Heating for 10 minutes, (c) thermocompressing the heated ion exchange membrane at 6,500-7,000 psi and 170-190 ° C. for 10-20 minutes, and (d) cutting the thermocompressed ion exchange membrane Obtaining an luminescent laminate, (e) coating an electrode on the surface of the luminescent laminate, and (f) forming an insulating layer by partially removing the electrode coating layer.

In addition, the (g) electrode coating step is carried out under a mixed solvent having a water and alcohol weight ratio of 100: 8-30, and (h) the insulating layer forming step is a plurality of electrode coating layers are the length of the lamp-shaped laminate It is characterized in that it is placed in a continuous or intermittent direction in the direction to be even in number so as to be opposed to the surface of the planar or curved surface facing each other. (A) First, a plurality of electroactive polymer ion exchange membranes are laminated. Specifically

6500-7000 psi pressure, low deformation under high temperature and high pressure of 170-190 ^° C, maintain shape and non-reflection with ion-exchange membrane, wire structure that can maintain constant diameter and have various cross-sectional shapes For example, wires, copper wires and lead wires can be used. The present invention is easy to adjust the diameter and is carried out using a wire in consideration of economics, but is not limited thereto. Such lamination preferably forms the same number of ion exchange membranes on the surface of the guide lamp.

 It may include a step of washing before laminating the electroactive polymer ion exchange membrane, the washing is to remove the dust, if fine dust remains on the surface may cause problems by inhibiting uniform and excellent electrode formation There is. Such washing may be performed one or more times, specifically about 1-5 times, using a nonpolar organic solvent such as n-nucleic acid, which is generally used in the art.

(B) The laminated ion exchange membrane is then heated ^at 170-190 ^° C. for 10-20 minutes. At this time, in order to prevent adhesion between the laminated silver exchange membrane and the thermocompression bonding, there is no deformation at the high temperature at which the thermocompression bonding is performed, and at the same time, after laminating the film which is not subjected to reaction with the ion exchange membrane, the thermocompression sheet is placed in Thermocompression is generally used in the art of stainless steel, and by controlling the thickness thereof, it is possible to control the thickness of the lamp laminate of the present invention. That is, it is preferable to maintain the thickness of 75-85% with respect to the thickness of the laminated electroactive polymer ion exchange membrane.

 The fluidity at the interface of the membrane is improved by the pretreatment of heating, and the conditions of the thermogravimetric analysis are the appropriate conditions in which the fluidity of the internal structure is ensured and the functional groups are not destroyed through the thermal characteristics of the ion exchange membrane. Thermogravimetry Analyzer (TGA) and differential scanning calorimeter (DSC).

When the temperature is less than 170 ^° C., the compressive force between the laminated films is significantly low, which may make it impossible to form a uniform laminated film. If the temperature exceeds 190 ^° C, the ion exchange membrane may melt or the interface between the surface and the film may be degraded. There is a problem to burn. In addition, if the time is less than 10 minutes, the ion exchange membrane may not adhere, and if it exceeds 20 minutes, it is preferable to maintain the above range because the interface between the surface and the film may burn.

Next, the heated ion exchange membrane was heated at 6 ᅳ 500-7,000 psi and 170-190 ^° C.

Perform thermocompression for 10-20 minutes. If the temperature is less than 170 ^° C or the pressure is less than 6500 psi, the compressive force between the laminated membrane is significantly low may not adhere to the ion exchange membrane, if it exceeds 190 ^° C or exceeds 7000 psi of the ion exchange membrane Uneven thickness or burning may occur.

 In addition, if the time is less than 10 minutes, the ion-exchange membrane may not adhere, and if it exceeds 20 minutes, burning may occur, so it is preferable to maintain the above range.

Next, (d) the thermocompression-bonded ion-exchange membrane is cut to obtain an equilateral laminate. In that the step of after the removal of impurities formed in the process of thermo-compression bonding to be included as additional bar, the removal of impurities is hydrogen peroxide cleaning procedure for specifically 5-6 hours at 60-100 ^° C, 90-120 ^° C 3-4 It performs a series of processes including a washing process, such as in aqueous solution for 3-4 hours in an aqueous solution during the time the cleaning process, and 6 coming from 100 ^° C aqueous solution of hydrochloric acid for 3-4 hours by a washing step and 90-120 ^° C. At this time, the hydrogen peroxide and hydrochloric acid solution is preferably maintained at a concentration of 5-15% by weight.

 Next, (e) an electrode is coated on the surface of the lamp stack. Coating of the electrode forms an electrode coating layer on the surface of the etc. laminate using the electroless plating method commonly used in the art.

 In this case, the electroless plating is carried out in a mixed solvent in which water and alcohol maintain a range of 100: 8-30 weight ratio, and in the case of the mixed solvent system, each of water, alcohol, etc. which are commonly used in the art. The volume increase rate of the ion exchange membrane is larger than that of the single solvent system, and the interface state between the electrode and the ion exchange membrane is improved, which contributes to the improvement of driving characteristics such as driving speed, driving displacement, and stepping speed of the polymer vibrator. Done.

 When the alcohol used in the mixed solvent is less than 8 weight ratio, the driving performance is increased than when using a single solvent of water, but the driving performance of the present invention may not be satisfied, and the amount of alcohol used is 30 weight ratio. If it exceeds, it is preferable to maintain the above range because the problem of separation of the thermally laminated film may occur.

Alcohols are alcohols having 1 to 6 carbon atoms that are commonly used in the art, specifically methane, ethanol, isopropanol, butanol, pentanol and nucleic acidol, preferably ethanol, methanol, more preferably ethane. It is good to use it.

 The thickness of the electrode coated in the above method is in the range of 10-30 / m, preferably 20-30

If the thickness range is less than 10 / m, the electrode formation is uneven and the driving performance may be degraded or not driven. It is preferable to maintain the above range because a problem may occur that the driving performance may be degraded due to the rigidity.

 Next, (f) an insulating layer is formed by partially removing the electrode coating layer. The insulating layer forming method may be performed using cutting, scratching, taping and masking, etc. which are generally used in the art, wherein the insulating layer has a thickness of 5 to 15 μνλ, preferably 7 to 12, in the opposite length direction. 2-8, preferably 4 can be formed.

 The present invention provides a catheter including the electroactive polymer vibrator as described above,

0.5-3.0 g _f or greater drive force, 40-90 ° drive displacement, 8X10— ⁷ Nm ^! The catheter has a strength of less than 0.25 g / cm ³ and a stepping speed of less than 2.0 mW / s and a diameter of 1.5 mW or less, and the catheter is used as the electroactive polymer vibrator and the active catheter for thrombolytic injection. It is characterized by being used. Specifically, the driving characteristics are described as 'above', 'below', 'less than', but the lower limit or upper limit of this range is limited to a range capable of performing a role as a driving body in the art.

 In addition, the thrombolytic method according to the present invention inserts the catheter into the thrombus and applies a current to vibrate the polymer vibrator to pulverize the thrombus, and at the same time to dissolve the thrombus by introducing a thrombolytic agent through the catheter, Hop in dissolved clots

It is characterized by performing (suet ion).

 Specifically, the catheter including the polymer vibrator according to the present invention is located in the thrombus surface or the inside of the catheter end, locally injected with drugs such as thrombolytics, or the catheter end is inserted into the thrombus after the voltage By applying the physical force generated in the vibrator can be pulverized thrombi. At this time, the vibration is generated by applying an alternating voltage to the vibrator, and when the thrombolytic agent is injected at the same time, it promotes permeation of the drug to improve the thrombolytic efficiency.

 The thrombolysis method using the electroactive polymer vibrator according to the present invention can dramatically accelerate the thrombolysis by synergistic effects of the two techniques by simultaneously using the physical stimulus and the thrombolytic administration, and also with the suction method. It can be used simultaneously.

The present invention evaluates driving characteristics such as driving force, driving displacement, and stepping speed for the manufacture of a vibrator that is optimally suitable for thrombosis. I can control the magnitude of the voltage It features.

 The driving force and driving displacement of the oscillator may be measured by measuring the magnitude of the applied voltage using a laser driver, and the response speed may be evaluated by measuring the response speed of the displacement with respect to the electrical signal. In this case, the chord speed means a mechanical response. The electrical response, which measures how long it starts to move when an electrical signal is given, occurs over a range, making it difficult to actually measure it. In the driving body, when the hydrated ions exert an electric stimulus from the outside, the driving is driven. Since the ion moving speed is less than that, the speed of the electrical moving in the driving body is also fast. The response speed of the drive was evaluated by setting the mechanical response as the basic time, and the time required to reach the point. The reaction time was measured in the unit of 'mm / s' by measuring the time taken to reach the limit of 15 인 which is the maximum measurement limit of the current drive displacement meter.

When AC voltage is applied to the vibrator, vibration occurs, and the vibration displacement and force are the physical characteristics such as elastic modulus or ductility coefficient of the vibrator, the magnitude and electrode characteristics of the voltage applied to the vibrator, and the ^' ion' Since the driving characteristics of the vibrator (force, displacement, quiescent velocity, etc.) change depending on various parameters such as movement, the oscillator must be driven in accordance with the characteristics of the thrombus and the dissolution method (drug administration, time limit, etc.). The dissolution efficiency can be improved. That is, by evaluating the driving characteristics of the vibrator, various parameters affecting the driving factors may be adjusted.

 Based on the disclosure of the present invention and common knowledge in the art, one of ordinary skill in the art will appreciate that the polymer vibrator may be modified by varying the group and mobility of the polymer groups used to produce the electroactive polymer vibrator at a given applied voltage. You can adjust the driving force, driving displacement, and stepping speed.

Although not explicitly stated in the specification of the present invention, the driving force, driving displacement, and response speed of the electroactive polymer vibrator when the 3 V voltage is applied are respectively 0.5-3.0 g _{f (} 40-90 ^° , 1). In the range of -1.5 mm / s, the lytic ability was excellent, whereas if any of the above three factors were out of the range, the thrombolytic activity was significantly decreased.

Therefore, in order to evaluate the thrombolytic activity of the electroactive polymer vibrator, the conventional electroactive polymer vibrator must be finally manufactured and then subjected to a complex hemolytic test. In addition, based on the disclosure of the present invention, the driving force, driving displacement, and response speed of an electroactive polymer vibrator under a 3 V applied voltage range of 0.5-3.0 g _f , 40-90 ^° , and 1-1.5-/ s, respectively. By checking whether or not the stomach has the advantage of predicting whether the actual thrombolytic properties are excellent.

 Therefore, according to another aspect of the present invention, in evaluating an electroactive polymer vibrator having excellent thrombolytic ability, it is characterized in that the use of the factors of the driving force, drive displacement, and response speed of the electroactive polymer vibrator A thrombolytic electroactive polymer vibrator screening method is disclosed.

According to a preferred embodiment, when the 3 V voltage is applied, the driving force, driving displacement, and response speed of the electroactive high molecular vibrator are 0.5-3 gf, 40-90 ^° , and 1-1.5 mA / s, respectively. An excellent hemolytic electroactive polymer vibrator screening method is disclosed that selects an electroactive polymer vibrator in the range.

 <90>

 Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. However, these examples are intended to illustrate the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited thereby.

 <92>

 <93> <Example>

 Example 1 Preparation of an Electroactive Polymer Oscillator

<95> A 180 mm thick Nafion (DuPonT, USA) was cut to 24 mm × 9 mm and then cleaned with n-nucleic acid to remove dirt on the surface of Nafion. The surface treated Napi was laminated with six membranes, and was laminated by inserting a wire having a diameter of 0.5 mm 3 between the third and fourth of the laminates. After that, the membrane was covered with a polyimide film having characteristics such as 50 thickness and heat resistance from above and below, and then stainless steel was placed in a 25 × X 50 × X0.93 mm height. At this time, it is possible to control the size of the Nafion membrane by adjusting the thickness of stainless steel. Later, the solution was placed on a hot-press and left unloaded at about 180 ^° C for about 12 minutes to improve fluidity under conditions where the functionalities of the internal structure of the Nafion membrane were not destroyed. These conditions were confirmed by TGA and DSC through the thermal properties of the Nafion membrane. Thereafter, a pressure of about 6700 psi was applied at about 180 ° C. for 10 minutes, and after the pressure was removed, the mold was separated from the hot-press. The silver is cooled at room temperature until the temperature of stainless steel On falling, the stacked Nafion membranes were separated at.

Next, the laminated napi was first stored in an aqueous solution for about 1 hour to remove impurities from the membrane. Afterwards, the four sides were cut out to form a rectangular shape with a knife to remove the messy ones on the four sides, and then the wires contained in the Nafion membrane were removed and boiled for about 5 hours at 10 weight> hydrogen peroxide at about 60 ^° C. . Thereafter, the membrane was boiled in an aqueous solution of 100 ^° C for about 3 hours, and boiled for about 3 hours in an aqueous solution of 10 wt% ¾> hydrochloric acid at 70 ^° C.

After the boiling process for about 3 hours in an aqueous solution of 100 ^° C. to prepare a laminate of Nafion membrane having a 2X1 匪² cross-section transparently laminated.

 In order to form a platinum electrode coating layer on the surface of the lamp-shaped laminate, first,

[Pt (NH ₃ ) ₄ ] The ion exchange membrane was impregnated with a mixed solvent of 100: 30 weight ratio of water and ethanol in which ₂ Cl ₂ platinum salt was dissolved at a concentration of 2 mg / ml. After 24 hours of impregnation, the ion exchange membrane was stirred at 100 rpm under a temperature of 40 ^° C., and electroless plating was performed under the condition that 5 ml of a mixed solvent of NaBH ₄ 5 >> was added 10 times every 30 minutes. In this case, the electrode coating layer was continuously positioned and was present on both opposite planes of the lamp stack.

 <99> and then cut off the top and bottom of the platinum electrode coating layer, each of the four side edges

 A high molecular vibrator was produced by forming an insulating layer by scraping off a thickness of 10 thick with a razor.

<ιοο> The vibrator prevents the decomposition of the material by blood flow and other stratification and blood contamination by the complex itself, and the paraline N (Di-para-Xylylene) and parline C (Di-Chloro- The combination of para-Xylylene) and paraline D (Tetra-Chloro-Para-Xylylene) was formed by encapsulation using thermal evaporation to form a polymer oscillator.

 <101>

 Example 2. Preparation of an Active Catheter for Electrophoretic Polymer Oscillator Injection According to the Present Invention

A drive body was manufactured in the same manner as in Example 1, but an enameled copper wire having a diameter of 0.08 mm, which was used as an electric wire, was welded at a high voltage to a polymer drive body having a structure of a luminaire having a drug administration duct therein. After that, the welded portion was sealed with a conductive adhesive. Then, the whole was coated with a heat-shrinkable polymer such as silicon, and the active tip was inserted at the end of the tube and then connected to make an active catheter.Palin N (Di-para-Xylylene) and Paraline C (Di-Chloro -para-Xylylene) and paraline lb

The combination of D (Tetra-Chloro-Para-Xylylene) was encapsulated by forming a capsule layer through thermal lamination.

 <104>

 <105> Comparative Example 1.

 It is prepared in the same manner as in Example 1 and Example 2, but the material of the capsule layer

 Encapsulated in a self-assembly monolayer (SAM).

 <107>

 <108> Comparative Example 2.

 Prepared in the same manner as in Examples 1 and 2, but the material of the capsule layer was encapsulated with a combination of polypropylene, urethane and silicone.

 <110>

<111><Pyeong7]^"Yes>

 Evaluation Example 1. Evaluation of Physical Properties of Electroactive Polymer Oscillator

<U3> In order to confirm the characteristics of the vibrator according to the present invention, a vibrator having a cross-sectional area of ² × ¹麵² was manufactured and evaluated. The driving force and the displacement were measured using a laser drive meter, and the sensitivity was measured by changing the position of the vibrator by applying an alternating voltage in the range of 1-10 Hz.

4 shows the shape and driving performance of a ² × ¹舰² sectional oscillator according to the present invention. a) is the width, b) the thickness, c) and d) are the actual measured thickness and width, e)

The sensitivity is 1, 5, and 10 Hz, and f) represents driving force.

In addition, the driving force was measured at different Hz and compared with the vibration frequency per minute.

 The results are shown in FIG. When more than 300 movements per minute were applied with a driving force of 0.3 gf or more, the optimal condition for thrombolytic dissolution was confirmed.

5116> The vibrator according to the present invention can be confirmed that the material exhibits excellent spherical power of 1 gf or more, which can be sensed at 10 Hz.

 <117>

 Evaluation Example 2. Evaluation of Characteristics of Capsule Layer

 <ιΐ9> The capsule formation of the electroactive polymer vibrators prepared in Examples 1 and 2 and Comparative Examples 1 and 2 and their properties were evaluated. Each manufactured vibrator was examined for its shape, thickness, and uniformity by electron scanning microscope, and the results are shown in the [Table]

1].

<120> [Table 1] ^

 <121>

 As shown in [Table 1], when capturing the vibrator to increase blood compatibility and bio stability, in Comparative Example 1, the thickness is thin, there is no effect as a coating layer, in the case of Comparative Example 2 The uniformity of the low and the separation phenomenon occurs in the junction, the encapsulation by adding the paraline-based coating layer according to the present invention can be confirmed that there is a uniform thickness, high bonding strength of the coating layer.

 <123>

 <124> <Experimental Example>

 Experimental Example 1. Confirmation of the thrombolytic ability of the thrombolytic method according to the present invention

 (1) Preparation of Experimental Thrombosis

 <127> 60 cc of dog venous blood are taken and placed in a 50 cc conical tube.

 Hematocrit was measured after immersing in an EDTA tube. A total of four dogs were used during the experiment, and the hematocrit value was 45-50%. Venous blood in dogs in conical lavage was incubated in a temp-controlled water bath (37 ° C) for 12-16 hours, and the serum was removed from the thrombi and the thrombus lysis test was performed using only the throttled thrombi. .

 <128>

 (2) Preparation of vascular panteam for experiment

 The acrylic glass tube having an inner diameter of 3.5 아크릴 was cut to 1.5 cm in length in the slide glass, and after adhesion, it was confirmed that there was no leakage in the adhesive part. When the fan team was manufactured, O.lg blood clots entered into the blood vessel fan team.

 l31>

 (3) Before the experiment, the blood compatibility of the electroactive polymer vibrator according to the present invention was confirmed through a hemolytic test.

As a test standard and method, hemolysis test was performed in the ISO 10933-4 hemocompatibiity test. Test material was DI for positive control and Saline for negative control. Blood was used within 24 hours after the animal was taken and anti-alcoholic agent was EDTA.

 As a result of the experiment, the average hemolysis degree is as shown in [Table 2] below, and the average hemolysis degree of OT was confirmed, and the oscillator according to the present invention was confirmed to have excellent blood compatibility.

 Mean Hemolysis (%) = (Test Solution Absorbance-Blank Test Absorbance) / (Positive Control Absorbance-Blank Test Absorbance) X 100

 <136> [Table 2]

 <137>

_¾ 138> (4) Comparison of Thrombus Solubility of the Vibrators According to the Invention

 <139> A 1.5 cm long, 2 mm wide electroactive polymer vibrator is used for the vascular phantom.

 After thrombosis of 0 / lg was added, the thrombolytic ability was measured. When thrombolytic rt-PA was added, 50 was added at a concentration of 0.1 mg / ml.

 The experiment was performed by dividing the group as shown in [Table 3] below, and the mean value of the thrombolytic increase rate was compared with the comparison group.

141> [Table 3]

In Table 3, it can be seen that even when only the vibrator according to the present invention is used without the addition of a thrombolytic agent, the thrombolytic ability is excellent. You can check it. When driving the vibrator according to the present invention under the above conditions, the average compared to the control

There is a 38% rise in thrombolysis.

 Even after the thrombolytic agent rt-PA was added, the 3 volt voltage -5HZ-5 minutes was the optimal condition for thrombolytic activity, and it can be seen that there is an average increase of thrombolysis rate of 82% compared to the control group.

Claims

[Range of request]

 [Claim 11

 (i) electrically conductive polymer laminates,

 (ii) a plurality of electrode coating layers present on a portion of the surface of the lampshade stack and

 (iii) an electroactive polymer vibrator comprising a capsule coating layer encapsulating said electrode coating layer;

 The electroactive polymer is selected from ionic polymers, conductive polymers, carbon nanotubes, dielectric polymers, electrostrictive polymers, nanoclays, silica compounds, and combinations thereof;

 The ionic polymer is a fluorine-based polymer having at least one ion group selected from a sulfonic acid group and a carbonyl group, and the fluorine-based polymer is one or a combination of two or more selected from the following:

-(CF ₂ CF)-(CF ₂ CF ₂ )-, (CH ₂ CF ₂ )-(GF ₂ CF).

O.CF ₂ CF (CF ₃ ) -O.CF ₂ CF ₂ CF _5- (CH ₂ CF ₂ )-

The conductive polymer is selected from polyaniline polypy, polysulfone, polyacetylene and combinations thereof;

 The dielectric polymer is selected from polyacrylates, silicones, polyvinylidene fluorides, and combinations thereof;

 The electromodified polymer is selected from polyacrylates, silicones, polyurethanes, and combinations thereof;

 The nanoclay is introduced with at least one subsequent group selected from sulfonated and carbonylated groups;

 The silica compound is selected from silica monomers modified through sulfonation or carbonylation and combinations thereof;

 The electrode is an electroactive polymer vibrator, characterized in that selected from platinum, gold, copper, silver, nickel, lead, cadmium and alloys thereof.

[Claim 2] The method of claim 1,

 The capsule coating layer is selected from paralin N (Di- para-Xylylene), paraline C (Di-Chloro_ para-Xylylene), paraline D (Tetra-Chloro-Para-Xylylene) and combinations thereof Electroactive polymer oscillator.

 [Claim 3]

 The method of claim 1,

 The plurality of electrode coating layers are continuously or intermittently positioned in the longitudinal direction of the columnar stack, and are present in an even number so as to be opposite to the surface of the planar or curved surface of the lamp stack, and have a diameter between the plurality of electrode coating layers. An electroactive polymer vibrator, characterized in that it is present and insulated.

 [Claim 4]

 The method of claim 3,

 The electroactive polymer vibrator is silicon-based on the electrode stack and the electrode coating layer and the electrode coating layer between the conductive polymer, carbon nanotubes and transition metal oxide single layer or two or more mixed layers and the electrode coating layer and the insulating layer. ， Epoch clock, Parylene-based and the polyurethane-based electro-active polymer oscillator, characterized in that it further comprises one or more layers selected from the coating layer.

 [Claim 5]

 The method of claim 1,

The electroactive polymer vibrator has a cross section of 0.6X0.6-1.0X1.0 mrf, has a length of 5- 15 Hz, a driving force of 0.5-3.0, a driving displacement of 40-90 ^°, and 1.01 ^at 1-20 Hz.

An electroactive polymer vibrator characterized by depressing at an equal speed of 1.5 瞧 / 3.

 [Claim 6]

 (a) stacking a plurality of electroactive polymer ion exchange membranes;

 (b) heating the laminated ion exchange membrane at 170-190 for 10-20 minutes;

(c) thermocompressing the heated ion exchange membrane at 6,500-7,000 psi and 170-190 for 10-20 minutes;

 (d) cutting the thermocompressed ion exchange membrane to obtain a columnar laminate;

(e) coating an electrode on the surface of the lamp stack; And

 (f) forming an insulating layer by partially removing the electrode coating layer, the method of manufacturing an electroactive polymer vibrator comprising:

The electroactive polymer is an ionic polymer, a conductive polymer, carbon nanotubes, oil Selected from malleable polymers, electrostrictive polymers, nanoclays, silica compounds, and combinations thereof;

 The ionic polymer is a fluorine-based polymer having at least one ion group selected from a sulfonic acid group and a carbonyl group, and the bloso-based polymer is one or a combination of two or more selected from the following:

= (CF ₂ GF)-(CF2CP ₂ )--(GH2CF2)-(GF2CF),

The conductive polymer is selected from polyaniline, polypy, polysulfone, polyacetylene and combinations thereof;

 The dielectric polymer is selected from polyacrylates, silicones, polyvinylidene fluorides, and combinations thereof;

 The electrostrain polymer is selected from polyacrylates, silicones, polyurethanes, and combinations thereof;

 The nanoclay is one in which one or more ionic groups selected from sulfonated and carbonyl groups are introduced;

 The silica compound is selected from silica monomers modified through sulfonation or carbonylation and combinations thereof;

 The electrode is a platinum, gold, copper, silver, nickel, lead, cadmium and an alloy thereof, the method of manufacturing an electroactive polymer vibrator, characterized in that.

 [Claim 7]

 The method of claim 6,

 (G) the electrode coating step is carried out under a mixed solvent having a water and alcohol weight ratio of 100: 8-30,

 The step (h) of forming the insulating layer may be performed such that a plurality of electrode coating layers are continuously or intermittently positioned in the longitudinal direction of the lamp stack, and are present in an even number so as to be opposite to the surface of the planar or curved surface facing the lamp stack. Method for producing electroactive polymer vibrator, characterized in that.

[Claim 8] As the catheter comprising the electroactive polymer transducer according to one of the preceding claims, 0.5-3.0 g _f or more driving force, the driving displacement of 40-90 ^°, 8X10- ^{7 Nm!} Has a strength of more than 0.25 g / cirf and a stepping speed of less than 2.0 mm / s with a diameter of 1.5 or less,

 The catheter is used as an active catheter for the electroactive polymer vibrator and thrombolytic injection.

 [Claim 9]

 In the method of thrombolysis,

 The thrombus is pulverized by inserting the catheter according to claim 8 into a thrombus and applying a current to vibrate the polymer vibrator,

 And at the same time discharging the thrombus by injecting a thrombolytic agent through the catheter, and then sucking the dissolved thrombus.

 [Claim 10]

For effective thrombolysis, the characteristics selected from the driving force, the driving displacement and the stepping speed of the electroactive polymer vibrator according to claim 1 are evaluated. The driving force (g _f ) is 0.5-3.0 g _f , and the driving displacement is 40-90 ^° A method selected from the type of ion groups present in the vibrator, the mobility of the ion groups, and the voltage increase applied to the vibrator so that the speed is 1.0—1.5 kHz / s.

 [Claim 11]

 In evaluating an electroactive polymer vibrator with excellent thrombolytic ability,

 Excellent thrombolytic electroactive polymer vibrator screening method, characterized in that the use of the driving force, drive displacement, step speed of the electroactive polymer vibrator.

 [Claim 12]

 The method of claim 11,

When the 3 V voltage is applied, the driving force, driving displacement, and response speed of the electroactive polymer vibrator are 0.5-3.0 g _f), respectively, in the range of 40-90 ^° and 1-1.5 隱 / s. An excellent thrombolytic electroactive polymer vibrator screening method characterized by selecting.