TW202428316A - Catheter set and system for site-directed release of therapeutic gas - Google Patents

Abstract

The present invention is related to catheter set and system for site-directed release of therapeutic gas and its system, in which the catheter set includes a catheter and an optic fiber disposed therein, the catheter has a reflective layer and is used for transporting photosensitive precursor and the therapeutic gas, and a light emitting end of the optic fiber is near the reflective layer of the catheter. When an administer opening is set at a target site, the therapeutic gas produced by excitation of the photosensitive precursor with the light beam can diffuse to the target site. The reflective layer is opaque and can increase the reflection times of the light beam in the catheter, thereby increasing the yield of the therapeutic gas. By using the catheter set, the therapeutic gas can be site-specific released in a desired location, so as to avoid the systemic side effects due to administering therapeutic gas.

Description

Catheter set and system for positioning and releasing therapeutic gas

The present invention relates to a catheter set for releasing gas, and more particularly to a catheter set and a system for releasing therapeutic gas in a positioned manner.

Therapeutic gases are medical gas molecules that can be used to provide medical needs, such as oxygen, nitrous oxide, nitric oxide, carbon monoxide and/or hydrogen sulfide. Therapeutic gases can be used as biosignals to regulate signal transduction pathways. For example, nitric oxide plays an important role in the signal transduction pathway of vasodilation, so it is often used to improve cardiovascular diseases, and carbon monoxide can suppress immune function, so it can be used to improve inflammatory responses.

However, if therapeutic gases are directly administered to the human body and/or the propellants of therapeutic gases are administered to the human body orally and/or sublingually, systemic side effects such as gas embolism may occur. Secondly, excessive doses of therapeutic gases are also dangerous to the human body. For example, excessive nitric oxide can cause low blood pressure and thus cause arrhythmia; carbon monoxide has a greater affinity for hemoglobin than oxygen, so excessive carbon monoxide will severely inhibit the function of red blood cells to carry and transport oxygen, thereby increasing the risk of tissue hypoxia.

Photodynamic therapy refers to the use of light beams to stimulate photosensitizers at target sites, so as to produce specific therapeutic effects at the desired location through active photosensitizers, wherein the photosensitizer can control the site of action, the range of action, and the dosage of the active photosensitizer by the location and intensity of light, respectively, thereby avoiding the above-mentioned systemic side effects and/or high-dose problems. However, light beams cannot penetrate the body, so photodynamic therapy is difficult to use in deep tissues, such as the heart.

Therefore, a method for releasing therapeutic gas in a targeted manner is urgently needed to solve the above problems.

Therefore, one aspect of the present invention is to provide a catheter assembly for positioning and releasing therapeutic gas, which includes a catheter and an optical fiber disposed in the catheter, wherein when the drug delivery port of the catheter is located at a target site, the therapeutic gas generated by the photosensitive precursor transmitted by the catheter stimulated by the light beam transmitted by the optical fiber can diffuse from the drug delivery port to the target site, and the catheter has a reflective layer, wherein the reflective layer is opaque and can increase the number of reflections of the light beam in the catheter, thereby improving the yield of the therapeutic gas.

Another aspect of the present invention is to provide a system of a catheter set for positioning and releasing therapeutic gas, comprising a supply element and the above-mentioned catheter and optical fiber, wherein the supply element serves as a light source and provides a photosensitivity precursor.

According to the above aspects of the present invention, a catheter assembly for positioning and releasing therapeutic gas is proposed, which includes a catheter and an optical fiber, wherein a reflective layer and a drug delivery port are sequentially arranged along the direction from the first end to the second end of the catheter, and the catheter is used to transmit a photosensitive precursor and a therapeutic gas. The above optical fiber is arranged in the catheter, wherein the optical fiber provides a light beam at the light output end, the light output end is adjacent to the reflective layer, and the reflective layer is opaque. When the drug delivery port is located at the target site, the therapeutic gas generated by the light beam exciting the photosensitive precursor diffuses from the drug delivery port to the target site.

In one embodiment of the present invention, the drug administration port is disposed at the second end of the catheter.

In one embodiment of the present invention, the drug administration port is disposed on the wall of the catheter.

In one embodiment of the present invention, a catheter assembly for positioning and releasing therapeutic gas may optionally include a guide wire disposed in the catheter, wherein the guide wire extends from a guide wire opening of the catheter wall to the second end of the catheter, the guide wire opening is disposed on the catheter wall between the reflective layer and the second end of the catheter, and the catheter is provided with a partition between the drug administration port and the guide wire opening.

In one embodiment of the present invention, the distance between the light-emitting end of the optical fiber and the drug-feeding port is 5 mm to 50 mm.

In one embodiment of the present invention, the reflective layer is attached to the outer side of the tube wall of the conduit, embedded in the outer side of the tube wall, buried in the tube wall, embedded in the inner side of the tube wall, or attached to the inner side.

According to another aspect of the present invention, a system for positioning and releasing therapeutic gas is proposed, which includes a supply element, a catheter and an optical fiber, wherein the supply element is used as a light source and provides a photosensitive precursor. The above-mentioned catheter is connected to the supply element at the proximal end of the catheter, wherein the catheter is sequentially provided with a reflective layer and a drug delivery port along the proximal end to the distal end of the catheter, and the catheter is used to transmit photosensitive precursors and therapeutic gas. The above-mentioned optical fiber is arranged in the catheter, wherein the optical fiber is optically connected to the supply element at the light input end of the optical fiber, and the optical fiber is used to transmit light from the light source to the light output end to form a light beam, and the light output end is adjacent to the reflective layer, and the reflective layer is opaque. When the drug delivery port is located at the target site, the therapeutic gas generated by the light beam exciting the photosensitive precursor diffuses from the drug delivery port to the target site.

In one embodiment of the present invention, the drug administration port is disposed at the distal end of the catheter.

In one embodiment of the present invention, the drug administration port is disposed on the wall of the catheter.

In one embodiment of the present invention, the system for positioning and releasing therapeutic gas may optionally include a guide wire disposed in the catheter, wherein the guide wire extends from a guide wire opening of the catheter wall to the far end of the catheter, the guide wire opening is disposed on the reflective layer and the catheter wall at the far end, and the catheter is provided with a partition between the drug administration port and the guide wire opening.

In one embodiment of the present invention, the length from the light-emitting end of the optical fiber to the drug delivery port is 5 mm to 50 mm.

In one embodiment of the present invention, the reflective layer is attached to the outer side of the tube wall of the conduit, embedded in the outer side of the tube wall, buried in the tube wall, embedded in the inner side of the tube wall, or attached to the inner side.

The catheter assembly for positioning and releasing therapeutic gas of the present invention uses a catheter to transmit a photosensitive precursor, uses an optical fiber to transmit a light beam, and sets a reflective layer in front of the drug delivery port of the catheter, wherein the reflective layer is opaque and can increase the number of reflections of the light beam in the catheter, thereby increasing the yield of the photosensitive precursor to position the therapeutic gas at the target site, and can perform photodynamic therapy deep into the patient's body, and avoid the occurrence of systemic side effects of direct and/or indirect administration of the therapeutic gas.

The following detailed description and the accompanying drawings are used to describe the embodiments of the present invention in detail. The same figure numbers used in the drawings and the specification refer to the same or similar parts as much as possible.

All documents cited herein are treated as if they were specifically and individually incorporated by reference by reference to each individual document or patent application. If a definition or use of a term in a cited document is inconsistent or contrary to the definition of that term herein, the definition of that term herein applies and does not apply to the definition of that term in the cited document.

As mentioned above, the present invention provides a catheter assembly for positioning and releasing therapeutic gas, which uses a catheter to transmit a photosensitive precursor and a therapeutic gas, and uses an optical fiber to provide a light beam, and a reflective layer is set in front of the drug delivery port, wherein the reflective layer is opaque and can increase the number of reflections of the light beam in the catheter, thereby improving the yield of the photosensitive precursor in the target area to position the therapeutic gas.

The "photosensitive precursor" described herein refers to particles that can form therapeutic gas after being irradiated with a light beam of a specific wavelength. In some embodiments, the photosensitive precursor can be, for example, a photosensitizer and/or a complex. In some embodiments, the above-mentioned complex can include a hydrophobic shell, a hydrophilic core coated in the hydrophobic shell, and a catalyst (not shown) embedded in the outer surface of the hydrophobic shell, wherein the hydrophilic core includes a therapeutic gas precursor. When the catalyst is irradiated with a light beam of a specific wavelength, it will resonate and generate heat and/or ultrasound, causing holes in the hydrophobic shell to release the therapeutic gas precursor in the hydrophilic core. When the therapeutic gas precursor contacts the hydrophobic shell, it can react with the precious metal nanoparticles to generate therapeutic gas.

In some embodiments, the therapeutic gas precursor may include but is not limited to S-nitrosothiols (RSNOs). In some specific examples, RSNOs may include but are not limited to S-nitrosoglutathione (GSNO), S-nitrosoalbumin (AlbSNO) and/or S-nitrosocysteine (CySNO). The hydrophobic shell may include a polymer, wherein the polymer is not particularly limited, and only needs to be an amphiphilic polymer having hydrophobicity and hydrophilicity. In some specific examples, the hydrophobic shell may be poly(lactic-co-glycolic acid, PLGA). The catalyst may be metal nanoparticles and/or metal ion compound nanoparticles, and the particle size thereof may be, for example, 1 nm to 30 nm. In some embodiments, the metal nanoparticles may include but are not limited to gold nanoparticles and/or silver nanoparticles. In other embodiments, the metal ion compound nanoparticles may include but are not limited to nanoparticles of Fe ²⁺ , Cu ²⁺ , Cu ⁺ , Ce ³⁺ , Cr ²⁺ and/or Mo ⁵⁺ . In some embodiments, the metal ion compound nanoparticles may be copper sulfide (Cu _{2- x} S, 0＜x＜1).

Please refer to FIG. 1, which is a partial longitudinal cross-sectional view of an exemplary catheter assembly 100 for positioning and releasing therapeutic gas according to an embodiment of the present invention. As shown in FIG. 1, the catheter assembly 100 for positioning and releasing therapeutic gas includes a catheter 110 and an optical fiber 200, wherein the optical fiber 200 is disposed in the catheter 110. The catheter 110 is provided with a reflective layer 150 and a drug delivery port 160 in sequence along a direction X from a first end 117 to a second end 119 of the catheter 110.

The optical fiber 200 provides a light beam (not shown) at the light output end 210, wherein the optical fiber 200 is adjacent to the reflective layer 150. The shape of the light output end 210 of the optical fiber 200 is not particularly limited. In some specific examples, the shape of the light output end 210 of the optical fiber 200 can be a plane (as shown in FIG. 2 ). In other embodiments, the light output end 210 of the optical fiber 200 has a plano-convex lens 230 or a prism (not shown) to form a more focused light beam. The diameter of the optical fiber 200 is not particularly limited. In some embodiments, the diameter of the optical fiber 200 can be, for example, 50 μm to 200 μm, or 100 μm to 150 μm, or 125 μm. In some embodiments, optical fiber 200 is flexible.

The material of the conduit 110 is not limited, as long as it can be used to transmit the photosensitive precursor and the therapeutic gas. In a specific example, the conduit 110 can be polyvinyl chloride, polytetrafluoroethylene, thermoplastic polyurethane, polyether ketone, polyethylene, polyether block amide and/or silicide. The diameter of the conduit 110 is not particularly limited, as long as it can accommodate the optical fiber 200 and the reflective layer 150 and allow the photosensitive precursor and the therapeutic gas to pass through. In a specific example, the diameter of the conduit 110 can be, for example, 100 μm to 500 μm.

In some embodiments, the drug delivery port 160 is the tube opening 120 of the catheter 110 located at the second end 119 of the catheter 110. In other embodiments, the drug delivery port 160 is located on the tube wall 130 of the catheter 110 (as shown in FIG. 2 ). There is no particular limitation on the opening shape and size of the drug delivery port 160, which only needs to allow the therapeutic gas precursor and/or the therapeutic gas to pass through. In some embodiments, the shape of the drug delivery port 160 can be circular and/or elliptical, and the diameter of the drug delivery port 160 can be, for example, 1 μm to 500 μm.

There is no particular limitation on the placement of the reflective layer 150 on the conduit 110. For example, the reflective layer 150 may be attached to the outer side 131 of the tube wall 130, embedded in the outer side 131 of the tube wall 130, buried in the tube wall 130 (as shown in FIG. 3 ), embedded in the inner side 133 of the tube wall, or attached to the inner side 133 of the tube wall 130. The material of the reflective layer 150 is not limited, as long as it is opaque and can be used to reflect light beams. In some embodiments, the material of the reflective layer 150 may include but is not limited to aluminum, silver, and/or copper.

Since the reflective layer 150 is opaque, the reflective layer 150 can increase the number of reflections of the light beam in the catheter 110, thereby increasing the yield of the therapeutic gas generated by the photosensitive precursor under the excitation of the light beam. In some embodiments, the distance D1 between the light output end 210 of the optical fiber 200 and the drug delivery port 160 is 5 mm to 50 mm, preferably 15 mm to 20 mm, so as to effectively increase the yield of the therapeutic gas and reduce the probability of the reflective layer 150 absorbing the therapeutic gas and forming large bubbles.

In actual use, the catheter set 100 for positioning and releasing therapeutic gas will extend the second end 119 into the patient's body cavity and/or blood vessel, and when the drug delivery port 160 is located at the patient's target site, the therapeutic gas generated by the light beam exciting the photosensitive precursor diffuses from the drug delivery port 160 to the target site. The "patient" described herein is not particularly limited, and can be used by anyone who needs to dilate blood vessels, for example, patients with cardiovascular damage and/or ischemic diseases. In some specific examples, the patient has angina caused by pulmonary embolism, coagulation embolism and/or coronary artery stenosis and needs emergency medical treatment.

In some embodiments, the catheter set for positioning and releasing therapeutic gas may optionally include a guide wire. Please refer to FIG. 2, which is a partial longitudinal cross-sectional view of an exemplary catheter set 300 for positioning and releasing therapeutic gas according to an embodiment of the present invention. As shown in FIG. 2, the catheter set 300 for positioning and releasing therapeutic gas includes a catheter 310 and an optical fiber 400, wherein the optical fiber 400 is disposed in the catheter 310. The catheter 310 is sequentially provided with a reflective layer 350 and a drug delivery port 360 along a direction X from a first end 317 to a second end 319 of the catheter 310, and the light-emitting end 410 of the optical fiber 400 is disposed in the reflective layer 350.

In this embodiment, the catheter 310 may optionally include a guide wire 510 disposed in the catheter 310, wherein the guide wire 510 may extend from a guide wire opening 560 on the tube wall 330 to the tube opening 320 of the second end 319 of the catheter 310, and the guide wire 510 has a guide wire hook 515 disposed outside the second end 319 of the catheter 310. There is no particular limitation on the position of the guide wire opening 560, as long as the guide wire 510 is prevented from interfering with multiple reflections of light on the reflective layer 350. In some embodiments, the guide wire opening 560 is disposed on the tube wall 330 between the reflective layer 350 and the second end 319 of the catheter 310. In the above-mentioned embodiment, a partition 570 is provided between the drug delivery port 360 and the guide wire port 560, so that the first end 317 of the catheter 310 and the second end 319 of the catheter 310 are not in liquid communication.

In actual application, the catheter 310 and the guide wire 510 enter the patient's blood circulation system from the radial artery of the patient's wrist and/or the femoral artery of the groin, so that the second end 319 of the catheter 310 moves to the affected part of the coronary artery along the guidance of the guide wire 510, and the drug delivery port 360 moves to the lesion. In some embodiments, it can be optionally used with a contrast agent and/or X-ray to confirm the location of the lesion and set the target site. In the above embodiment, the reflective layer 350 can be used as a radiation shielding mark to mark the location of the drug delivery port 360.

In other examples, the catheter may optionally include a microfluidic tube. Please refer to Figure 3, which is a partial longitudinal cross-sectional view of an exemplary catheter set 600 for positioning and releasing therapeutic gas according to an embodiment of the present invention. As shown in Figure 3, the catheter set 600 for positioning and releasing therapeutic gas includes a catheter 610, a microfluidic tube 605 disposed in the catheter 610, and an optical fiber 700, wherein the catheter 610 is sequentially provided with a reflective layer 650 and a drug delivery port 660 along a direction X from the first end 617 of the catheter 610 to the second end 619. As shown in Figure 3, the reflective layer 650 is buried in the tube wall 630 of the catheter 610, and the drug delivery port 660 is at the tube mouth 620 at the second end 619. It should be understood that the embodiment shown in Figure 3 is only an example and is not intended to limit the present invention. The microfluidic tube 605 and the optical fiber 700 are disposed adjacent to each other. The microfluidic tube 605 is used to transmit a photosensitive precursor, and the liquid outlet 609 of the microfluidic tube 605 is adjacent to the reflective layer 650. The optical fiber 700 provides a light beam at the light outlet 710, and the light outlet 710 is adjacent to the reflective layer 650. The relative positions of the liquid outlet 609 and the light outlet 710 are not limited, and can be, for example, in the same plane, or the distance between the liquid outlet 609 and the drug delivery port 660 is greater than the distance between the light outlet 710 and the drug delivery port 660, wherein the distances can be, for example, 5 mm to 50 mm, respectively, to increase the yield of the therapeutic gas.

Please refer to FIG. 4 , which is a schematic diagram of an exemplary system 900 for positioning and releasing therapeutic gas according to the present invention. As shown in FIG. 4 , the system 900 for positioning and releasing therapeutic gas includes a supply element 910, a catheter 810, and an optical fiber (not shown), wherein the catheter 810 is connected to the supply element 910 at a proximal end 817 of the catheter 810, and the optical fiber (not shown) is disposed in the catheter 810. The optical fiber (not shown) and the catheter 810 are as described in the exemplary catheter set 100 for positioning and releasing therapeutic gas and the exemplary catheter set 300 for positioning and releasing therapeutic gas, and will not be described in detail here.

The conduit 810 is used to deliver photosensitivity precursors and therapeutic gases. In some embodiments, the supply element 910 may optionally include a storage tank 911, a drug pump 913, a processor 915, and a light source supplier 917, wherein the processor 915 is electrically connected to the drug pump 913 and the light source supplier 917, and the drug pump 913 is fluidically connected to the storage tank 911, so that the drug pump 913 controls the flow rate of the photosensitivity precursor from the storage tank 911 to the far end 819 of the conduit 810. The flow rate is not particularly limited and may be determined depending on the concentration of the photosensitivity precursor, the cross-sectional area of the fluid, and/or the desired yield of the therapeutic gas. In one embodiment, when the diameter of the catheter 810 is 100 μm to 500 μm, the flow rate may be, for example, 50 μL/min to 400 μL/min.

The optical fiber (not shown) is optically connected to the supply element 910 to transmit light from the light source supply 917 of the supply element 910 to the light output end (not shown) to form a light beam. The wavelength of the light provided by the light source supply 917 is not particularly limited, and it only needs to be able to excite the photosensitive precursor and generate therapeutic gas. In some embodiments, when the photosensitive precursor is the above-mentioned complex whose catalyst is nano-gold particles, the light source provides green light (wavelength of 500 nm to 560 nm) with an optical power of 5 mW to 150 mW.

Animal experiments have shown that the above-mentioned catheter set for positioning and releasing therapeutic gas can effectively provide therapeutic gas (such as nitric oxide) to the target site, thereby achieving the desired effect (such as dilating the diameter of blood vessels) at the target site. It is worth noting that in vitro experiments have shown that the production rate of therapeutic gas in the catheter set with a reflective layer is increased compared to the catheter set without a reflective layer.

Several examples are used below to illustrate the application of the present invention, but they are not intended to limit the present invention. A person skilled in the art can make various modifications and improvements without departing from the spirit and scope of the present invention. Example 1: Evaluation of light power and nitric oxide yield

The GSNO/nano-gold-PLGA complex was prepared by the method described in patent TW I616211. First, an oil phase solution containing PLGA at a concentration of 10 mg/mL was prepared with dichloromethane, and an aqueous phase solution containing GSNO at a concentration of 5×10 ^-3 M was prepared with water. In the first emulsification process, the oil phase solution was slowly poured into the aqueous phase solution, and ultrasonic treatment was performed at the same time, and then ice bathed for 2 hours to obtain a first emulsified solution containing water/oil (w/o). In the second emulsification process, a nanogold particle solution with a particle size of about 4 nm and a concentration of 200 ppm prepared with dichloromethane was added dropwise to the first emulsified solution, and then placed in an ice bath for 20 minutes, thereby obtaining a GSNO/nanogold-PLGA complex with a particle size of about 500 nm (hereinafter referred to as a photosensitizer).

After irradiating the sample solution containing the photosensitive precursor with a light beam of 7 mW, 25 mW, 45 mW and 102 mW at a wavelength of 532 nm for 25 seconds, the nitric oxide content in the sample solution was detected using the Nitric Oxide Colorimetric Assay Kit (BioVision K262-200), as briefly described below. Nitric oxide has low stability and easily forms nitrate and nitrite. Therefore, nitrate reductase can be added to the sample solution to convert the nitrate in the sample solution into nitrite, and then Griess reagent is added for color treatment to form a dark purple azo compound. The absorbance value of the sample solution at a wavelength of 540 nm can be detected, and the amount of nitric oxide released can be calculated using the standard curve. The standard curve is drawn by subjecting standard solutions of nitrite of different concentrations to the above color treatment and then plotting the absorbance of the standard solutions under light of the same wavelength.

Please refer to FIG. 5, which is a bar graph showing the amount of nitric oxide released after the photosensitizer according to one embodiment of the present invention is irradiated with light beams of different light powers, wherein the horizontal axis represents the light power (unit: mW), the vertical axis represents the amount of nitric oxide released (unit: nmol), and the percentage on the bar represents the percentage of photosensitizer that is stimulated. As shown in FIG. 5, when the light power is 7 mW, 3.4 nmol of nitric oxide can be released, which is equivalent to stimulating 22.3% of the photosensitizer, and the higher the light power, the higher the nitric oxide production. Example 2: Evaluation of changes in the diameter of brain blood vessels in rats after using the catheter group

The diameter of the rat's brain blood vessels was measured using brain angiography, which involves injecting a contrast agent into the rat's brain blood vessels and then taking X-rays. Next, the catheter set (as shown in Figure 1) was inserted into the rat's brain blood vessels from the rat's femoral artery, with the drug delivery port of the catheter set set at the target position, and the photosensitive precursor was delivered through the catheter. Then, the optical fiber was used to transmit light with a wavelength of 532 nm and a light power of 7 mW, so that after 25 seconds of light irradiation, the photosensitive precursor produced nitric oxide that diffused in the rat's brain blood vessels, thereby locating the release of therapeutic gas. Then, the diameter of the rat's brain blood vessels was measured again using the above-mentioned brain angiography. It is worth noting that in the photos taken using brain angiography, the color of brain blood vessels is darker, so the signal intensity of brain blood vessels will be lower than the background value. In the same shooting window, the reference axis and reference point are defined, and the diameter of the blood vessel can be measured by the length between the starting position and the end position where the signal is lower than the background value. The reference axis is perpendicular to the wall of the target blood vessel, and the reference point is located on the reference axis at the background.

Please refer to Figure 6, which is a line graph showing the signal intensity on the reference axis of the rat's brain blood vessels before and after the therapeutic gas is released through a catheter assembly according to one embodiment of the present invention, wherein the horizontal axis represents the distance from the above-mentioned reference point (unit: μm), the vertical axis represents the signal intensity (unit: arbitrary unit, a.u.), and the broken line 961 and the broken line 963 respectively represent the diameter of the blood vessel before the therapeutic gas is released through positioning (broken line 961) and the diameter of the blood vessel after the therapeutic gas is released through positioning (broken line 963). As shown in FIG6 , after the therapeutic gas was released through the catheter group, the diameter of the blood vessels in the rat brain increased by about 50 μm, indicating that the catheter group can indeed release the therapeutic gas in a targeted manner, thereby achieving the corresponding effect of the therapeutic gas. Example 3: Evaluation of the optimal flow rate of different concentrations of photosensitizer precursors

In this embodiment, the same concentration of photosensitive precursor (the concentration of gold nanoparticles contained therein is 625 ppm) is transmitted by controlling the catheter set at different flow rates, and optical fibers are used for illumination to form nitric oxide in physiological saline water, and then the concentration of nitric oxide released in the physiological saline water is detected by a nitric oxide colorimetric analysis kit.

Please refer to Figure 7, which is a bar graph showing the concentration of nitric oxide released at different flow rates according to different concentrations of photosensitizers of one embodiment of the present invention, wherein the horizontal axis represents the flow rate (unit: μL/min), the vertical axis represents the nitric oxide concentration (unit: μM), and the straight bar 971 and the straight bar 973 respectively represent the catheter group with a reflective layer and the catheter group without a reflective layer.

As shown in FIG. 7 , when the flow rate is 200 μL/min and the catheter is provided with a reflective layer (bar 710 ), the generated nitric oxide concentration is higher, indicating that the catheter is provided with a reflective layer and the flow rate is 200 μL/min, which is a better condition for performing photodynamic therapy.

In summary, the above-mentioned specific photosensitive precursors, specific lighting conditions, specific catheter configurations, specific processes or specific evaluation methods are only used to illustrate the catheter set and system for positioning and releasing therapeutic gas of the present invention. However, those with ordinary knowledge in the art to which the present invention belongs should understand that other photosensitive precursors, other lighting conditions, other catheter configurations, other processes or other evaluation methods can also be used for positioning and releasing therapeutic gas The catheter set and system and are not limited to the above without departing from the spirit and scope of the present invention.

As can be seen from the above-mentioned embodiments, the catheter assembly and system for positioning and releasing therapeutic gas of the present invention have the advantages of using a catheter to transport a photosensitive precursor to a target site, and then using an optical fiber to perform an illumination step, wherein the catheter is provided with a reflective layer, and the reflective layer is opaque, which can increase the number of reflections of the light beam in the catheter, thereby improving the yield of the therapeutic gas. Therefore, the therapeutic gas can be released at the target site, and the content of the therapeutic gas produced can be controlled by controlling the flow rate, concentration and/or optical power of the photosensitive precursor, thereby avoiding the systemic side effects caused by direct and/or indirect administration of the therapeutic gas and/or the side effects of excessive therapeutic gas.

Although the present invention has been disclosed as above with several specific embodiments, various modifications, changes and substitutions may be made to the above disclosed contents, and it should be understood that, without departing from the spirit and scope of the present invention, certain features of the embodiments of the present invention will be adopted in certain situations but other features will not be used accordingly. Therefore, the spirit and scope of the claims of the present invention should not be limited to the above exemplary embodiments.

100,300,600: catheter assembly for positioning and releasing therapeutic gas 110,310,610,810: catheter 117,317,617: first end 119,319,619: second end 120,320,620: tube opening 130,330,630: tube wall 131: outer side 133: inner side 150,350,650: reflective layer 160,360,660: drug delivery port 200,400,700: optical fiber 210,410,710: light output end 230: plano-convex lens 510: guide wire 515: guide wire hook 560: guide wire opening 570: separator 605: microfluidic tube 609: liquid outlet 817: proximal end 819: distal end 900: system for positioning the release of therapeutic gas 910: supply element 911: storage tank 913: drug pump 915: processor 917: light source supply 961,963: broken line 971,973: straight line X: direction D1: distance

In order to make the above and other purposes, features, advantages and embodiments of the present invention more clearly understood, the detailed description of the attached drawings is as follows: FIG1 is a partial longitudinal cross-sectional view of an exemplary catheter set for positioning and releasing therapeutic gas according to an embodiment of the present invention. FIG2 is a partial longitudinal cross-sectional view of an exemplary catheter set for positioning and releasing therapeutic gas according to an embodiment of the present invention. FIG3 is a partial longitudinal cross-sectional view of an exemplary catheter set for positioning and releasing therapeutic gas according to an embodiment of the present invention. FIG4 is a schematic diagram of an exemplary system for positioning and releasing therapeutic gas according to the present invention. FIG5 is a bar graph showing the amount of nitric oxide released after a photosensitive precursor according to an embodiment of the present invention is irradiated with light beams of different light powers. Fig. 6 is a line graph showing the signal intensity on the reference axis of the rat brain blood vessels before and after photodynamic therapy with a catheter set according to one embodiment of the present invention. Fig. 7 is a bar graph showing the concentration of nitric oxide released at different flow rates by different concentrations of photosensitizer precursors according to one embodiment of the present invention.

100: Catheter set for positioning and releasing therapeutic gas

110: Catheter

117: First End

119: Second end

120: pipe mouth

130: Tube wall

131:Outer side

133:Inside

150:Reflective layer

160: Medication port

200: Optical fiber

210: Light output end

230: Plano-convex lens

D1: Distance

X: Direction

Claims (12)

A catheter assembly for positioning and releasing therapeutic gas comprises: a catheter, wherein a reflective layer and a drug delivery port are sequentially arranged along a first end of the catheter toward a second end, and the catheter is used to transmit a photosensitive precursor and the therapeutic gas; and an optical fiber, arranged in the catheter, wherein the optical fiber provides a light beam at a light output end, the light output end is adjacent to the reflective layer, and the reflective layer is opaque, and wherein when the drug delivery port is located at a target site, the light beam excites the photosensitive precursor to generate a therapeutic gas that diffuses from the drug delivery port to the target site. A catheter assembly for positioning and releasing therapeutic gas as described in claim 1, wherein the drug delivery port is disposed at the second end of the catheter. A catheter assembly for positioning and releasing therapeutic gas as described in claim 1, wherein the drug delivery port is disposed on a tube wall of the catheter. The catheter assembly for positioning and releasing therapeutic gas as described in claim 3 further includes a guide wire arranged in the catheter, wherein the guide wire extends from a guide wire opening on a tube wall of the catheter to the second end of the catheter, the guide wire opening is arranged on the tube wall between the reflective layer and the second end of the catheter, and the catheter is provided with a partition between the drug administration port and the guide wire opening. A catheter assembly for positioning and releasing therapeutic gas as described in claim 1, wherein the length of the light-emitting end of the optical fiber from the drug delivery port is 5 mm to 50 mm. A catheter assembly for positioning and releasing therapeutic gas as described in claim 1, wherein the reflective layer is attached to an outer side of a tube wall of the catheter, embedded in the outer side of the tube wall, buried in the tube wall, embedded in an inner side of the tube wall, or attached to the inner side. A system for positioning and releasing therapeutic gas, comprising: a supply element, used as a light source and providing a photosensitive precursor; a catheter, wherein the catheter is connected to the supply element at a proximal end of the catheter, the catheter is provided with a reflective layer and a drug delivery port in sequence along the proximal end of the catheter to a distal end, and the catheter is used to transmit the photosensitive precursor and the therapeutic gas; and an optical fiber, disposed in the catheter, wherein the optical fiber is optically connected to the supply element at a light input end of the optical fiber, the optical fiber is used to transmit light from the light source to a light output end to form a light beam, the light output end is adjacent to the reflective layer, and the reflective layer is opaque, and When the drug delivery port is located at a target site, the light beam excites the photosensitive precursor to generate a therapeutic gas that diffuses from the drug delivery port to the target site. A system for positioning and releasing a therapeutic gas as described in claim 7, wherein the drug delivery port is located at the distal end of the catheter. A system for positioning and releasing therapeutic gas as described in claim 7, wherein the drug delivery port is disposed on a wall of the catheter. The system for positioning and releasing therapeutic gas as described in claim 7 further includes a guide wire disposed in the catheter, wherein the guide wire extends from a guide wire opening in a tube wall of the catheter to the far end of the catheter, the guide wire opening is disposed on the reflective layer and the tube wall at the far end of the catheter, and the catheter is provided with a partition between the drug administration port and the guide wire opening. A system for positioning and releasing therapeutic gas as described in claim 7, wherein the length of the light-emitting end of the optical fiber from one end of the drug administration port is 5 mm to 50 mm. A system for positioning and releasing therapeutic gas as described in claim 7, wherein the reflective layer is attached to an outer side of a tube wall of the conduit, embedded in the outer side of the tube wall, buried in the tube wall, embedded in an inner side of the tube wall, or attached to the inner side.

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