Patent Description:
Thrombolytic therapy for general vascular thrombosis mainly relies on drugs, including anticoagulants and thrombolytic agents. A thrombolytic agent, such as a tissue plasminogen activator (Tpa), is taken as an example herein. The Tpa is an anticoagulant that was first approved by the US Food and Drug Administration (FDA) to treat thrombusinduced stroke. However, the Tpa also has serious defects. Thrombolytic drugs have the risk of causing bleeding, the Tpa must be used within hours of the onset of stroke symptoms, the drug effect in the body can not be long-lasting and may cause long-lasting bleeding, and large blood clots can not be dissolved usually. If high-dose thrombolytic drugs are used, it is easy to cause massive bleeding in the body. In addition, patent document <CIT> discloses an ultrasonic device for transversely manipulating drug delivery carriers and method using the same; patent document <CIT> discloses a method and apparatus for drug delivery to a target site; patent document <CIT> discloses a method and apparatus for treatment of intracranial hemorrhages; and patent document <CIT> discloses a method and apparatus for accelerated disintegration of blood clot.

Generally, ultrasonic waves refer to generally-focused or non-focused ultrasonic waves. In the technical field of ultrasonic emission, it is a general prior art to generate an ultrasonic focusing effect by phase modulation. In order to reduce the dose of thrombolytic drugs and the risk of bleeding and consider the thrombolytic effect, an interventional catheter is used for directly delivering the thrombolytic agents to the thrombus, and general ultrasonic waves are used for strengthening the drugs to ablate the thrombus so as to strengthen the thrombolytic effect. However, general phase modulation does not have the thrombolytic technology for generating a vortex acoustic field by phase modulation of the present invention.

Based on the above, the present invention adopts phase modulation to generate a vortex acoustic field, and the general phase modulation and the phase modulation of the present invention for generating the vortex acoustic field are two completely different technologies. The probe for transmitting the vortex acoustic field is provided with a piezoelectric patch, the piezoelectric patch comprises a plurality of channels, and the phase difference generated between every two channels is used for generating a vortex of an acoustic channel by the ultrasonic transducer. In brief, although the two technologies are based on phase modulation, the objectives are different.

The problem to be solved by the present invention is that the technology for generating a vortex acoustic field through phase modulation makes the present invention superior to the general ultrasonic combined thrombolytic drug technology to improve the efficiency in a thrombolytic method.

Further developments are defined by the dependent claims.

In order to further understand the objectives, effects, features and structures of the present invention, exemplary embodiments in conjunction with accompanying drawings are illustrated below.

<FIG> is a schematic diagram of a vortex catheter thrombolytic system with an ultrasonic transducer, <FIG> is a schematic diagram of a vortex catheter thrombolytic system, and <FIG> is a schematic diagram of a vortex catheter thrombolytic system. <FIG> illustrate aspects of the disclosure but are not according to the claimed embodiment. Referring to <FIG> and <FIG>, in an embodiment of the present disclosure, a vortex catheter thrombolytic system <NUM> comprises an ultrasonic transducer <NUM>; and a probe <NUM> for transmitting a vortex acoustic field as well as a catheter <NUM>, wherein the catheter <NUM> is arranged in the probe <NUM> for transmitting the vortex acoustic field, is connected to the ultrasonic transducer <NUM> and is provided with a first inner channel <NUM> and a second inner channel <NUM>, the first inner channel <NUM> is used for delivering drugs, the second inner channel <NUM> is used for vortex driving, the probe <NUM> for transmitting the vortex acoustic field is provided with a piezoelectric patch <NUM>, the piezoelectric patch <NUM> comprises a plurality of channels, and the phase difference generated between every two channels is used for generating a vortex <NUM> of an acoustic channel by the ultrasonic transducer <NUM>.

Referring to <FIG> and <FIG>, in an embodiment of the present disclosure, a vortex catheter thrombolytic system <NUM> comprises an ultrasonic transducer <NUM>; and a probe <NUM> for transmitting a vortex acoustic field as well as a catheter <NUM>, wherein the catheter <NUM> is arranged in the probe <NUM> for transmitting the vortex acoustic field, is connected to the ultrasonic transducer <NUM> and is provided with a first inner channel <NUM> and a second inner channel <NUM>, the first inner channel <NUM> is used for delivering drugs, the second inner channel <NUM> is used for vortex driving, the probe <NUM> for transmitting the vortex acoustic field is provided with a piezoelectric patch <NUM>, the piezoelectric patch <NUM> comprises a plurality of channels, and the phase difference generated between every two channels is used for generating a vortex <NUM> of an acoustic channel by the ultrasonic transducer <NUM>.

Specifically, the ultrasonic transducer <NUM> can be a pulse generator. More specifically, the ultrasonic transducer <NUM> can be, but not limited to, a pulse generator based on a field programmable gate array (FPGA). Furthermore, a driving signal transmitted by the ultrasonic transducer <NUM> can be a square wave signal or a sine wave signal. Although not shown in the figures, an amplifier can be arranged on the ultrasonic transducer <NUM> to amplify the driving signal.

In an embodiment of the present disclosure, the piezoelectric patch <NUM> is made from a lead zirconate titanate material. Furthermore, the piezoelectric patch <NUM> and a filling and sealing casing are filled with epoxy resin, but the present invention is not limited thereto.

In an embodiment of the present invention, the probe <NUM> for transmitting the vortex acoustic field can be connected with the catheter <NUM> in a magnetic adsorption mode, a buckling mode or a gluing mode.

In an embodiment of the present invention, the probe <NUM> for transmitting the vortex acoustic field comprises at least one piezoelectric patch <NUM> or comprises multiple array elements (at least four array elements) of piezoelectric patches <NUM>, the piezoelectric patch <NUM> has a curved shape and is cut into four adjacent channels, and the phase difference generated between every two adjacent channels is used for generating an acoustic vortex.

In an embodiment of the present invention, the curvature radius of the piezoelectric patch ranges from <NUM> to <NUM>.

<FIG> is a schematic diagram of a vortex catheter thrombolytic system according to an embodiment of the present invention. Referring to <FIG> and <FIG>, in an embodiment of the present invention, a vortex catheter thrombolytic system <NUM> comprises an ultrasonic transducer <NUM>; and a radial probe <NUM> for transmitting a vortex acoustic field as well as a catheter <NUM>, wherein the catheter <NUM> is arranged in the radial probe <NUM> for transmitting the vortex acoustic field, is connected to the ultrasonic transducer <NUM> and is provided with a first inner channel <NUM> and a second inner channel <NUM>, the first inner channel <NUM> is used for delivering drugs, the second inner channel <NUM> is used for vortex driving, the radial probe <NUM> for transmitting the vortex acoustic field can perform vortex motion at two sides so as to increase the vortex driving to the radial direction of blood vessels, the radial probe <NUM> for transmitting the vortex acoustic field is provided with a piezoelectric patch <NUM>, the piezoelectric patch <NUM> comprises a plurality of channels, and the phase difference generated between every two channels is used for generating a vortex <NUM> of an acoustic channel by the ultrasonic transducer <NUM>.

In an embodiment of the present invention, the radial probe <NUM> for transmitting the vortex acoustic field comprises at least one piezoelectric patch <NUM> or comprises multiple array elements (at least four array elements) of piezoelectric patches <NUM>, the piezoelectric patch <NUM> has a curved shape and is cut into four adjacent channels, and the phase difference generated between every two adjacent channels is used for generating an acoustic vortex.

<FIG> is a flow diagram of a thrombolytic method in which an embodiment of the invention may be employed. Referring to <FIG>, a thrombolytic method comprises: performing an ultrasonic execution step through the vortex catheter thrombolytic systems <NUM>, <NUM> and <NUM> so as to generate an acoustic vortex; executing a focusing step so as to focus a drug delivery carrier to the center of the acoustic vortex; and executing a manipulation step so as to manipulate the drug delivery carrier to a lesion area.

The ultrasonic execution step is executed by a pulse generator having a duty cycle of <NUM>% or higher.

The parameters in the ultrasonic execution step are as follows: the frequency is <NUM>-<NUM>, and the acoustic pressure ranges from <NUM> MPa to <NUM> MPa.

Referring to <FIG>, in S510, the ultrasonic execution step is performed through the vortex catheter thrombolytic system so as to generate an acoustic vortex.

Referring to <FIG>, in S520, the focusing step is executed so as to focus a drug delivery carrier to the center of the acoustic vortex.

Referring to <FIG>, in S530, the manipulation step is executed so as to manipulate a drug delivery carrier to a lesion area.

Thrombus is a blood clot formed in blood vessels and acts in a blood circulation system to obstruct or block blood flow. When the blood vessels are damaged, in order to avoid blood loss or further damage to the blood vessels caused by blood flow impact, platelets and fibrin in the blood will aggregate to form the blood clot for repairing. However, if the blood clot falls off, it may cause thrombosis to cause embolism.

Preparation of thrombus <NUM> and simulation of blood flow:
The blood of the human body is divided into plasma and erythrocyte. The plasma accounts for about <NUM>% of the total blood volume, and the erythrocyte accounts for about <NUM>% of the total blood volume. The thrombus can also be prepared by using whole blood. The thrombus in this experiment is prepared from the whole blood of the human body. There may be some slight differences between individuals, and the concentration of calcium chloride can be finely adjusted.

A thrombus preparation formula in the experiment does not require a special ratio and basically comprises <NUM>% of plasma and <NUM>% of erythrocyte. The experiment can also be performed according to the data provided by the medical corporate body Taiwan Blood Services Foundation.

Step <NUM>: plasma, erythrocyte and thrombin 20U were placed in a constanttemperature water tank and heated to <NUM>.

Step <NUM>: the plasma, the erythrocyte, the thrombin 20U and calcium chloride (CaCl<NUM>) were sequentially added in proportion.

Step <NUM>: after mixing, a syringe was fixed by a floating pad and placed at the water temperature of <NUM> for <NUM> to form a thrombus to be pushed out by the syringe.

Step <NUM>: an Actilyse solution has a function of dissolving the thrombus <NUM>, a solution containing Actilyse (scientific name: Alteplase) was used as a thrombolytic drug (Tpa) in this experiment, the prepared thrombus was added to the thrombolytic drug prepared from the Actilyse solution, then, a solidified state was changed into a flow state, and a peristaltic pump was used for generating a flow environment so as to simulate the blood flow.

Thrombolytic experiment method:
At the simulated body temperature of <NUM>, three groups of experiment conditions (one control group and two experiment groups) were provided: a thrombolytic drug (Tpa), a general ultrasonic wave combined thrombolytic drug (Tpa), and a vortex acoustic field combined thrombolytic drug (Tpa). In order to compare the difference between the control group and the experiment groups, the experiment conditions were fixed and dissolved for <NUM> for comparison, and the thrombolytic effects of all groups were obtained by comparing the residual dose of thrombus dissolution.

Thrombolytic drug (Tpa): the thrombolytic drug was added to the thrombus <NUM>, and the residual dose of thrombus dissolution was calculated <NUM> later.

General ultrasonic wave combined thrombolytic drug (Tpa): general ultrasonic waves were applied to the thrombus <NUM> under the conditions that the pressure was <NUM> MPa and the duty cycle was <NUM>%, and the residual dose of thrombus dissolution was calculated <NUM> later.

Vortex acoustic field combined thrombolytic drug (Tpa): a vortex acoustic field was applied to the thrombus <NUM> under the conditions that the pressure was <NUM> MPa and the duty cycle was <NUM>%, and the residual dose of thrombus dissolution was calculated <NUM> later.

<FIG> shows a dissolution rate of a thrombolytic experiment under three experiment conditions.

The dissolution rate of the thrombolytic experiment under three experiment conditions: experiment group <NUM>: the dissolution rate of the vortex acoustic field combined thrombolytic drug (Tpa) was <NUM>%; experiment group <NUM>: the dissolution rate of the general ultrasonic wave combined thrombolytic drug (Tpa) was <NUM>%; and control group: the dissolution rate of the thrombolytic drug (Tpa) was <NUM>%. The results of many experiments show that the thrombus dissolution rate of the experiment group <NUM> was increased by more than <NUM>% compared with the experiment group <NUM>, and the difference was significant; and the thrombus dissolution rate of the experiment group <NUM> was increased by more than <NUM>% compared with the control group, and the difference was also significant.

The results of many experiments show that the thrombolytic effect of the vortex acoustic field combined thrombolytic drug (Tpa) was better than that of the general ultrasonic wave combined thrombolytic drug (Tpa), more than <NUM>% of the thrombus dissolution rate was increased, and the difference was significant; and the thrombolytic effect of the vortex acoustic field combined thrombolytic drug (Tpa) was better than that of the single thrombolytic drug (Tpa), more than <NUM>% of the thrombus dissolution rate was increased, and the difference was also significant. The experiments prove that the dissolution rate of the vortex acoustic field combined thrombolytic drug (Tpa) applied to thrombus dissolution was better than that of other prior arts.

The experiments prove that the dissolution rate of the vortex acoustic field combined thrombolytic drug (Tpa) applied to the thrombolytic experiment was better than that of other prior arts.

The probe for transmitting the vortex acoustic field or the radial probe for transmitting the vortex acoustic field of the present invention can enhance the vortex driving effect and achieve the objective of quick thrombus dissolution.

Therefore, the present invention has excellent advancement and practicability in similar products.

Claim 1:
A vortex catheter thrombolytic system (<NUM>), comprising an ultrasonic transducer (<NUM>), a radial probe (<NUM>) for transmitting a vortex acoustic field, and a catheter (<NUM>), wherein:
the catheter (<NUM>) is connected to the ultrasonic transducer (<NUM>) and is provided with a first inner channel (<NUM>) and a second inner channel (<NUM>), the first inner channel (<NUM>) is configured for delivering drugs, the second inner channel (<NUM>) is provided with a piezoelectric patch (<NUM>) on the radial probe (<NUM>) configured for vortex driving, and the piezoelectric patch (<NUM>) comprises four channels, characterized in that:
the four channels are disposed in a radial direction of the catheter (<NUM>), wherein a phase difference between any two adjacent channels of the piezoelectric patch (<NUM>) is configured for generating an acoustic vortex (<NUM>) in the radial direction of the catheter (<NUM>) by the ultrasonic transducer (<NUM>);
the piezoelectric patch (<NUM>) is enveloped in the catheter (<NUM>) and is not exposed out of the catheter (<NUM>); and
a delivering exit where the drugs are delivered out is adjacent to the acoustic vortex (<NUM>) generated by the piezoelectric patch (<NUM>), whereby the drugs are delivered out and focused on a center of the acoustic vortex (<NUM>) in the radial direction of the catheter (<NUM>).