CN119258365A

CN119258365A - Catheter systems for transarterial chemoembolization and photodynamic therapy

Info

Publication number: CN119258365A
Application number: CN202411590728.4A
Authority: CN
Inventors: 邢凌之; 陈玲; 袁仪; 廖国佳; 鲁绍聪; 李乐泰; 陈丽媛; 李佳洲; 贺诗绮; 高毓成
Original assignee: Chongqing Medical University
Current assignee: Chongqing Medical University
Priority date: 2024-11-08
Filing date: 2024-11-08
Publication date: 2025-01-07

Abstract

The invention provides a catheter system for arterial chemoembolization and photodynamic therapy, which comprises a catheter main body capable of being inserted into an artery, namely an inner tube and an outer tube which is annularly arranged outside the inner tube, wherein a cavity for storing and conveying medicines is formed inside the inner tube, an optical fiber connected with a laser light source is arranged between the inner tube and the outer tube, and laser energy conducted by the optical fiber is output through the front end between the inner tube and the outer tube. The inner tube is used for releasing chemical medicines, embolic materials and photosensitizers, and laser output by the optical fiber between the inner tube and the outer tube is used for activating the photosensitizers in tumor tissues, and TACE and PDT are realized at the same time. The invention applies PDT to clinic treatment of liver cancer for the first time, combines the PDT and TACE in a catheter system, can simultaneously carry out TACE and PDT through one-time intubation, the innovative compound interventional therapy technology combines the minimally invasive interventional medicine and photodynamic therapy technology, increases the feasibility of treating deep tumors of the liver, reduces the intubation times of patients, and simplifies the treatment flow.

Description

Catheter system for arterial chemoembolization and photodynamic therapy

Technical Field

The invention belongs to the technical field of medical appliances, and particularly relates to a catheter system for arterial chemoembolization and photodynamic therapy.

Background

Trans-arterial chemoembolization (TACE) and photodynamic therapy (PDT) are two effective topical treatments for tumors.

TACE achieves direct killing and interruption of blood supply to tumor cells by delivering chemotherapeutic drugs and embolic material directly to the tumor blood supply artery, such as the microcatheter for Transcatheter Arterial Chemoembolization (TACE) as disclosed in CN201710103523.2, a catheter for hepatic arterial perfusion chemotherapy as disclosed in CN202321780835.4, or a sub-abdominal wall arterial chemoindwelling catheter as disclosed in CN 201120315174.9. However, due to the uneven blood supply characteristics of the tumor and the distribution of the chemotherapeutic agent, certain areas may not obtain sufficient drug concentration, such that the therapeutic effect is uneven, often resulting in treatment failure or recurrence.

PDT is a technology of diagnosing and treating diseases by using photodynamic effect, firstly marking target tissue cells with a photosensitive substance, then irradiating with laser with a specific wavelength, activating a photosensitizer to generate Reactive Oxygen Species (ROS), and the excessive ROS can cause oxidation damage to mitochondria and DNA of cancer cells, thereby killing the cancer cells, such as a light guide rod and a photodynamic therapeutic apparatus for photodynamic therapy disclosed in CN202120619251.3 or a therapeutic apparatus for photodynamic therapy disclosed in CN 202322170145.3. The aggregation and activation of photosensitizers in tumor tissues is the key of PDT, mainly ultraviolet light or visible light is used as an excitation light source, however photons in the wavelength range are easily absorbed or quenched by biological tissues, so that the tissue penetration depth is low, PDT treatment is severely limited, and photodamage effect of the biological tissues is extremely easy to be caused, so that the application of PDT is limited to the treatment of superficial parts or small-volume tumors, and the PDT is difficult to be widely applied to deep parts of organisms.

In clinical application, TACE is quite mature in clinical treatment of liver cancer, while PDT is still mainly in research stage, the apparatus of the above-mentioned publication is non-invasive, and is difficult to be widely applied to deep part of organism, and liver cancer is tumor of deep part of organism, so that PDT has not been widely applied to clinical treatment of liver cancer. Therefore, there is a need for an innovative composite interventional catheter system that can combine TACE with PDT to improve therapeutic efficacy and expand the application potential of PDT in liver cancer treatment.

Disclosure of Invention

The invention aims to solve the technical problems that the arterial chemoembolization and photodynamic therapy in the prior art lack of a catheter system with high efficiency integration, are inconvenient to operate, have limited treatment effect, cannot act on the deep part of the body and the like, and aims to provide the catheter system for arterial chemoembolization and photodynamic therapy.

The invention adopts the following technical scheme that the catheter system for arterial chemoembolization and photodynamic therapy comprises a catheter main body capable of being inserted into an artery, wherein the catheter main body comprises an inner tube and an outer tube which is annularly arranged outside the inner tube, a cavity for storing and conveying medicines is formed in the inner tube, a medicine outlet communicated with the cavity is formed at the front end of the inner tube, a medicine adding port communicated with the cavity is formed in the inner tube, an optical fiber connected with a laser light source is arranged in a space between the inner tube and the outer tube, and light output by the optical fiber can be output through the front end between the inner tube and the outer tube.

According to the technical scheme, when TACE is carried out, the inner tube is used for releasing chemical medicines and embolic materials and delivering the chemical medicines and embolic materials to the blood supply artery of the tumor. When in PDT, the inner tube is used for conveying photosensitizer, and the laser emitted by the optical fiber between the inner tube and the outer tube is used for activating photosensitizer in tumor tissue to generate active oxygen and kill tumor cells. The invention realizes PDT of the deep part of the organism in a minimally invasive intervention mode by arranging the optical fiber between the inner tube and the outer tube, applies photodynamic therapy (PDT) to clinical treatment of liver cancer in the intervention mode for the first time, is interventional photodynamic therapy, combines TACE and PDT in a catheter system, can perform TACE and PDT by one-time intubation, reduces the intubatton times of patients, simplifies the treatment process and improves the comfort level of the patients. The invention creatively fuses photodynamic therapy (PDT) with arterial chemoembolization (TACE), is an innovative compound interventional therapy technology, and belongs to the category of comprehensive treatment strategies.

In a preferred embodiment of the invention, a micro valve for controlling the release rate is provided at the dispensing orifice and/or a closure cap for closing the dispensing orifice is provided at the dispensing orifice.

According to the technical scheme, the micro valve is arranged, the opening degree of the micro valve is adjusted to control the release speed of medicines (including chemotherapeutic medicines, embolic materials and photosensitizers), so that the medicines can be rapidly and accurately released in TACE and PDT processes, and external pollutants are prevented from entering the cavity by arranging the sealing cover, so that the medicine dispensing device is more sanitary.

In a preferred embodiment of the present invention, the optical fiber is a solid optical fiber or a hollow optical fiber, the optical fiber includes a plurality of optical fibers provided in a space between the inner tube and the outer tube, the plurality of optical fibers being circumferentially spaced along an outer circumference of the inner tube, or the optical fiber includes one hollow optical fiber provided in a space between the inner tube and the outer tube.

The technical scheme provides two implementation modes of arranging a plurality of optical fibers and a hollow optical fiber, and the implementation modes can be selected according to actual conditions.

In a preferred embodiment of the invention, the end of the optical fiber is tapered.

According to the technical scheme, the tail end of the optical fiber is conical, so that the divergence angle of light can be increased, the laser can deeply irradiate tumor tissues, and the effectiveness of photodynamic therapy is improved.

In a preferred embodiment of the present invention, a light guide prism is disposed at the front end between the inner tube and the outer tube, and the light output from the optical fiber can be emitted through the light guide prism to form a light spot.

According to the technical scheme, the laser angle emitted by the optical fiber is adjusted by the light guide prism, so that different treatment requirements are met.

In another preferred embodiment of the invention, the front end of the inner tube extends out of the outer tube, the front end of the inner tube is hemispherical, and the front end of the outer tube and the outer wall of the inner tube are in smooth transition.

According to the technical scheme, the hemispherical transition and the smooth transition are more beneficial to the insertion of the catheter main body into the artery compared with the plane and the steps, and the damage to patients is reduced.

In another preferred embodiment of the present invention, the drug outlet is a side hole provided in a side wall of the inner tube extending to the outside of the outer tube.

According to the technical scheme, the medicine outlet hole is formed in the side wall of the inner tube, and the damage of the side wall of the medicine outlet hole to a patient can be reduced when the catheter main body is inserted into an artery.

In another preferred embodiment of the invention, the front end inside the inner tube is further provided with a guide head for guiding the insertion of the catheter body into the artery, which guide head is connected to the monitoring device, and with force-conducting identification means.

According to the technical scheme, the guide head and the force conduction identification device are arranged, so that the state of the catheter main body can be observed in real time in the penetrating and positioning processes, the measurement of the direction and the size is realized, the catheter main body is accurately positioned to the near end of tumor tissues (such as liver cancer cells and liver malignant tumors), the normal blood vessels beside the tumor tissues are not influenced, and the damage to a patient is reduced.

In another preferred embodiment of the invention, the end part of the outer tube far away from the medicine outlet is fixedly connected with a wire seat positioned outside the inner tube, the input end of the optical fiber passes through the wire seat and is connected with a plug, and the optical fiber is connected with a laser light source through the plug.

According to the technical scheme, the wire seat plays a role in guiding and limiting, so that the optical fiber can smoothly pass out of the outer tube, and the plug connector is arranged so that the optical fiber can be connected with the laser light source quickly.

Compared with the prior art, the better technical scheme of the invention has the following beneficial effects:

1) The novel integrated design is that TACE and PDT are combined in a catheter system, so that the synergistic effect of the two treatment methods is realized, the novel composite interventional treatment technology combines the minimally invasive interventional medicine and the photodynamic therapy technology, the uniformity and pertinence of the treatment effect are improved, the feasibility of treating deep tumors of the liver is improved, the PDT therapy is used for the clinical treatment of the deep tumors (such as liver cancer) for the first time, the application of the photodynamic therapy in the treatment of hepatocellular carcinoma is promoted, and a safer and more effective new treatment choice is provided for patients.

2) And in the accurate treatment, the accurate delivery of the chemotherapy drugs and the embolic materials and the photodynamic therapy are combined, so that the treatment effect on the hepatocellular carcinoma is improved, and the recurrence rate is reduced.

3) The operation flow is simplified, the integrated design of the catheter system is simplified, TACE and PDT can be carried out by one intubation, the intubation times of a patient are reduced, the treatment process is simplified, the medical risk of the patient is reduced, the convenience and the comfort of treatment are improved, and the overall treatment experience of the patient is improved.

Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.

Drawings

The foregoing and/or additional aspects and advantages of the invention will become apparent and may be better understood from the following description of embodiments taken in conjunction with the accompanying drawings in which:

fig. 1 is a schematic structural diagram of a catheter system for arterial chemoembolization and photodynamic therapy according to the first embodiment.

Fig. 2 is a schematic diagram in partial cross-section A-A in fig. 1.

Fig. 3 is a schematic diagram showing A-A in fig. 1 in partial cross-section.

Fig. 4 is a schematic structural diagram of a catheter system for trans-arterial chemoembolization and photodynamic therapy according to the second embodiment.

The reference numerals in the drawings of the specification comprise a catheter main body 1, an inner tube 2, a cavity 21, a medicine outlet 22, a medicine adding port 23, an outer tube 3, an optical fiber 4, a wire guide seat 5, a plug connector 6, a guide head 7 and a light guide prism 8.

Detailed Description

Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functions throughout. The embodiments described below by referring to the drawings are illustrative only and are not to be construed as limiting the invention.

In the description of the present invention, it should be understood that the terms "longitudinal," "transverse," "vertical," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," and the like indicate or are based on the orientation or positional relationship shown in the drawings, merely to facilitate description of the invention and to simplify the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be configured and operated in a particular orientation, and thus should not be construed as limiting the invention.

In the description of the present invention, unless otherwise specified and defined, it should be noted that the terms "mounted," "connected," and "coupled" are to be construed broadly, and may be, for example, mechanical or electrical, or may be in communication with each other between two elements, directly or indirectly through intermediaries, as would be understood by those skilled in the art, in view of the specific meaning of the terms described above.

Example 1

The present invention provides a catheter system for arterial chemoembolization and photodynamic therapy, as shown in fig. 1, in a preferred embodiment, the catheter system comprises a catheter body 1 capable of being inserted into an artery, the rear end (the upper end shown in fig. 1) of the catheter body 1 is connected with an operation handle for an operator to hold and operate the motion of the catheter body 1, the catheter body 1 is a microcatheter made of biocompatible materials, has good flexibility and is convenient for intravascular operation, such as the materials of the microcatheter disclosed in CN201710103523.2, which is the prior art and is not described in detail herein.

The catheter main body 1 comprises an inner tube 2 and an outer tube 3 which is arranged outside the inner tube 2 in a surrounding way, and the inner tube 2 and the outer tube 3 are round tubes and are coaxially arranged. The inside of the inner tube 2 has a plurality of cavities 21 extending in the longitudinal direction thereof in parallel for delivering the medicine, the front end (lower end shown in fig. 1) of the inner tube 2 has a medicine outlet 22 communicating with each cavity 21, and the rear end of the inner tube 2 has a medicine feeding port 23 communicating with each cavity 21. An optical fiber 4 connected with an external laser light source is arranged in the space between the inner tube 2 and the outer tube 3, the front end between the inner tube 2 and the outer tube 3 is closed and made of a light-transmitting material, and light output by the optical fiber 4 can be output through the front end between the inner tube 2 and the outer tube 3. The optical fiber 4 is a hollow optical fiber or a solid optical fiber, and the material of the optical fiber can be the prior art, which is not an innovation point of the present invention and is not described in detail herein.

When the catheter system is used, the catheter body 1 is inserted into an artery (such as a hepatic artery, for treating hepatocellular carcinoma) of a patient under the guidance of imaging, so that the position is accurate, and the specific insertion method can be adopted in the prior art.

Drug and embolic material release during TACE procedure drug enters the cavity 21 in the inner tube 2 from the drug port 23, specifically drug can be injected into the cavity 21 from the drug port 23 by a drug pump or syringe, chemotherapeutic drug is directly delivered to the tumor blood supply artery from the drug outlet hole 22 through the cavity 21, and embolic material (such as microspheres, gelatin sponge) is released through the cavity 21 to block the blood supply to the tumor.

The PDT process activates photodynamic therapy by delivering a photosensitizer to the tumor tissue through the cavity 21, after which the laser source is turned on, providing laser light of a specific wavelength, directing the laser light to an optical fiber 4 surrounding between the inner tube 2 and the outer tube 3, the optical fiber 4 emitting laser light to the tumor tissue, the laser activating the photosensitizer, generating reactive oxygen species, further damaging the tumor cells.

In the treatment process, the blood flow state and illumination intensity of the liver need to be monitored in real time, and the drug release and laser intensity are adjusted if necessary, so that the optimal treatment effect is ensured.

In order to facilitate insertion of the catheter body 1, the guide wire may be provided for guiding, and conventional techniques in the art are not described in detail herein. In addition, the catheter system may be provided in a variety of sizes depending on age, sex, type of disease, etc.

When the patient is inserted into a vascular access, the patient is normally in a supine position, the puncture part is disinfected, spread with towel and locally infiltrated for anesthesia, a femoral access is usually selected, a radial access can be selected if the patient is conditional, percutaneous puncture is usually performed by adopting a SE L D I NGER method, and a catheter sheath is arranged. In angiography, abdominal artery or hepatic common artery is imaged, and the imaging image acquisition should include arterial phase, parenchymal phase and venous phase. If the blood vessel in the liver area is scarce or deficient or the tumor is incompletely stained, the superior mesenteric artery, the left gastric artery, the inferior diaphragmatic artery, the renal artery, the internal thoracic artery, the intercostal artery, the lumbar artery and other arteries should be made for angiography to find the lateral branch and supply blood vessel of the hepatic artery and the extrahepatic artery with ectopic origin.

All blood supply arteries of the tumor need to be searched and defined in the operation, and a Cone Beam CT (CBCT) examination is recommended, and the contrast performance is carefully analyzed in combination with the preoperative imaging examination to define the tumor part, size, number and condition of the blood supply arteries (evidence grade 2, recommended intensity A). Attention is also paid to the effect of different contrast parameters on the DSA image. For severe cirrhosis, portal arterial trunk and primary branch cancer embolism, indirect portal vein imaging via superior mesenteric artery or splenic artery is recommended, and portal blood flow is known.

The present invention is provided with a plurality of cavities 21 extending in the longitudinal direction thereof in parallel inside the inner tube 2. When the chemotherapeutic medicine and the embolic material need to be separately delivered, the chemotherapeutic medicine and the embolic material can be delivered by two cavities 21 respectively, when the chemotherapeutic medicine and the embolic material can be delivered simultaneously or the two cavities 21 need not to be separately delivered, the mode of the chemotherapeutic medicine and the embolic material needs to be determined according to clinical decision, the photosensitive agent can react with the chemotherapeutic medicine or influence the effect, the photosensitive agent is delivered by the other cavity which is parallel, when X-ray development is adopted, the inner tube 2 can be used for adding contrast agent, at the moment, a parallel cavity needs to be additionally arranged for delivering the contrast agent, and when X-ray development is not adopted, the cavity for independently delivering the contrast agent can not be arranged.

In another preferred embodiment, a micro valve (not shown) for controlling the release rate is arranged at the drug outlet 22, and the opening of the micro valve is controlled to control the release amount and the release rate of the drug during chemotherapy, so that the chemotherapeutic drug and the embolic material can be released rapidly during TACE. Preferably, the dosing opening 23 is provided with a cover for closing the dosing opening, and the cover is detachably connected with the dosing opening 23, such as in a threaded connection or a clamping connection.

In the present invention, as shown in fig. 1, the front end of the inner tube 2 extends out of the outer tube 3, the drug outlet hole 22 is a side hole formed in the side wall of the inner tube 2 extending out of the outer tube 3, the front end of the inner tube 2 is hemispherical, and the front end of the outer tube 3 and the outer wall of the inner tube 2 are smoothly transited, so that the catheter body 1 can be smoothly inserted into an artery.

In another preferred embodiment, the front end inside the inner tube 2 is further provided with a guiding head 7 connected to a monitoring device for guiding the catheter body 1 to be inserted into an artery, and specifically, the catheter body 1 can be guided to be inserted into an artery by means of ultrasonic imaging, optical imaging or electrophysiological imaging, which are all prior art and are not described in detail herein. It is further preferred that the front end of the inner tube 2 is provided with a powerful conductive identification means (not shown in the figures), such as a way of identifying the front end force of a guide wire used for an optical fiber interventional guide wire for tip multidimensional force measurement as disclosed in CN202310253782.9, which is prior art and not described in detail herein.

As shown in fig. 1, in the present invention, the end of the outer tube 3 far from the drug outlet 22 is fixedly connected with a wire seat 5 located outside the inner tube 2, the input end of the optical fiber 4 passes through the wire seat 5 and is connected with a plug 6, and the optical fiber 4 is connected with a laser light source through the plug 6. When in use, the plug connector 6 is connected with the laser light source, so that the optical fiber 4 is quickly connected with the laser light source. Preferably, the plug connector 6 adopts a quick-release connector, so that the plug connector is convenient to detach and maintain.

In one embodiment, the optical fibers 4 comprise a plurality of optical fibers disposed in the space between the inner tube 2 and the outer tube 3, the plurality of optical fibers 4 being circumferentially spaced along the outer circumference of the inner tube 2, as shown in fig. 2, and in one embodiment, the optical fibers 4 comprise one hollow optical fiber disposed in the space between the inner tube 2 and the outer tube 3, as shown in fig. 3.

In another preferred embodiment, the end of the optical fiber 4 is tapered to increase the divergence angle of the light.

Example two

The structural principle of this embodiment is basically the same as that of the first and second embodiments, except that, as shown in fig. 4, in this embodiment, a light guide prism 8 is disposed at the front end between the inner tube 2 and the outer tube 3, the light guide prism 8 is fixedly connected (e.g. glued) to the inner wall of the outer tube 3, and the light output by the optical fiber 4 can be emitted and form a light spot after passing through the light guide prism 8 to irradiate the tumor part. In practice, according to different treatment requirements, different light guide prisms 8 may be configured to change the angle of the laser beam output from the optical fiber 4, for example, a condensing prism (fresnel lens) is used to concentrate the laser beam energy output from the optical fiber 4, and a diverging prism (powell prism) is used to diverge and uniformly disperse the laser beam output from the optical fiber 4 to the edge.

In the description of the present specification, reference to the terms "preferred implementation," "one embodiment," "some embodiments," "example," "a particular example" or "some examples" and the like means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the spirit and scope of the invention as defined by the appended claims and their equivalents.

Claims

1. A catheter system for transarterial chemoembolization and photodynamic therapy, characterized in that it comprises a catheter body that can be inserted into an artery, the catheter body comprising an inner tube and an outer tube arranged around the inner tube;

The inner tube has a plurality of parallel cavities extending along its length for delivering drugs, the front end of the inner tube has a drug outlet communicating with each cavity, and the inner tube is also connected to a drug adding port communicating with each cavity;

An optical fiber connected to a laser light source is arranged in the space between the inner tube and the outer tube, and the light output by the optical fiber can be output through the front end between the inner tube and the outer tube.

2. The catheter system for transarterial chemoembolization and photodynamic therapy according to claim 1, characterized in that a microvalve for controlling the release rate is provided at the drug outlet;

And/or the drug adding port is provided with a sealing cover for sealing the drug adding port.

3. The catheter system for transarterial chemoembolization and photodynamic therapy according to claim 1, characterized in that the optical fiber is a solid optical fiber or a hollow optical fiber;

The optical fiber includes a plurality of solid optical fibers arranged in the space between the inner tube and the outer tube, and the plurality of optical fibers are arranged circumferentially at intervals along the outer circumference of the inner tube; or the optical fiber includes a hollow optical fiber arranged in the space between the inner tube and the outer tube.

4 . The catheter system for transarterial chemoembolization and photodynamic therapy according to claim 1 , wherein the end of the optical fiber is a tapered structure.

5. The catheter system for transarterial chemoembolization and photodynamic therapy according to any one of claims 1 to 4, characterized in that a light-guiding prism is provided at the front end between the inner tube and the outer tube, and the light output by the optical fiber can be emitted after the light-guiding prism and form a light spot.

6. The catheter system for transarterial chemoembolization and photodynamic therapy according to any one of claims 1 to 4, characterized in that the front end of the inner tube extends out of the outer tube, the front end of the inner tube is hemispherical, and the front end of the outer tube smoothly transitions to the outer wall of the inner tube.

7. The catheter system for transarterial chemoembolization and photodynamic therapy according to claim 6, characterized in that the drug outlet hole is a side hole provided on the side wall of the inner tube extending out of the outer tube.

8. The catheter system for transarterial chemoembolization and photodynamic therapy according to any one of claims 1 to 4, characterized in that the front end of the inner tube is also provided with a guide head connected to a monitoring device for guiding the catheter body to be inserted into the artery, and a force conduction identification device.

9. The catheter system for transarterial chemoembolization and photodynamic therapy according to any one of claims 1 to 4, characterized in that the end of the outer tube away from the drug outlet is fixedly connected to a wire holder located outside the inner tube, the input end of the optical fiber passes through the wire holder and is connected to a plug connector, and the optical fiber is connected to the laser light source through the plug connector.