Photodynamic balloon catheter system

Abstract

The application discloses a kind of photodynamic balloon catheter systems, comprising: tube body, with opposite proximal end and distal end;Balloon, the balloon is fixed in the distal end portion of the tube body;Optical fiber assembly is inserted in the tube body, and with the light-emitting site extending to adjacent the balloon;The surface of the balloon is loaded with auxiliary material and photosensitizer in the form of coating;The photosensitizer can activate collagen and elastin under the wavelength of light 400-460nm to make them crosslink;The auxiliary material includes active drug and sustained-release material wrapped the active drug, the active drug is at least one of paclitaxel, rapamycin, zotarolimus, tacrolimus, everolimus, temsirolimus, zanolimus, biolimus, docetaxel, protein-bound paclitaxel and protein-bound dexamethasone;By the photodynamic balloon catheter system of the application can improve the utilization rate of active drug in intravascular administration.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and in particular to a photodynamic balloon catheter system. Background Technology

[0002] Vascular diseases are now among the leading causes of death in humans. Most vascular diseases, whether organic or functional, are fundamentally characterized by ischemic changes in organs due to narrowing or occlusion of blood vessels. Currently, angiogenesis is one of the important methods for restoring blood flow to narrowed blood vessels.

[0003] Drug-loaded balloon catheter systems are commonly used interventional devices in angiogenesis procedures, widely applied to treat vascular stenosis and occlusion. The mechanism of action of a drug-loaded balloon catheter system involves loading a drug onto the surface of a balloon. Using interventional techniques, the coiled balloon is delivered to the lesion site, and external devices drive the balloon to inflate and contact the vessel wall. This allows the drug on the balloon surface to be rapidly released and transferred to the local vessel wall. The drug can be at least one of two types: drugs that form microsclerosis in situ (e.g., photosensitizers) and active drugs that act on diseased cells (e.g., paclitaxel). When the balloon is loaded with a drug that forms microsclerosis in situ, the balloon catheter system also needs to be equipped with a photodynamic device that emits a specific wavelength to promote the formation of microsclerosis on the vessel wall.

[0004] However, current research has found that although drug-loaded balloon catheter systems improve the targeting accuracy of active drugs, the concentration change trend of active drugs in vivo is not ideal, and the utilization rate of active drugs needs to be improved. Summary of the Invention

[0005] To address the aforementioned technical problems, this application provides a photodynamic balloon catheter system that can enhance the efficacy of active drugs.

[0006] The photodynamic balloon catheter system in this application includes:

[0007] The tube body has a relatively proximal end and a distal end;

[0008] A balloon, the balloon being fixed to the distal end of the tube;

[0009] An optical fiber assembly is inserted into the tube and has a light-emitting portion extending to the vicinity of the balloon;

[0010] The surface of the balloon is coated with excipients and photosensitizers;

[0011] The photosensitizer can activate collagen and elastic fibers at a light wavelength of 400-460nm, causing them to cross-link.

[0012] The excipients include an active pharmaceutical ingredient and a sustained-release material encapsulating the active pharmaceutical ingredient, wherein the active pharmaceutical ingredient is at least one of paclitaxel, rapamycin, zotamolimus, tacrolimus, everolimus, tamsulolimus, zoromolimus, biolimus, docetaxel, protein-bound paclitaxel, and protein-bound dexamethasone.

[0013] Several alternative methods are provided below, but they are not intended as additional limitations on the overall solution above. They are merely further additions or optimizations. Provided there are no technical or logical contradictions, each alternative method can be combined individually with respect to the overall solution above, or multiple alternative methods can be combined with each other.

[0014] Optionally, in the excipients, the mass ratio of the active drug to the sustained-release material is 1:1 to 1:20. Preferably, it is 1:10.

[0015] Optionally, the mass ratio of the photosensitizer to the active drug is 1:0.2 to 5. Preferably, it is 1:0.5.

[0016] Optionally, the photosensitizer is porphyrin, phthalocyanine, chlorine, purine, 5-hydroxyacetic acid, 1,8-naphthalimide, 1,8-naphthalimide polymer, dinaphthalimide compound, 2,2'-((ethane-1,2-di(oxy))bis(ethane-2,1-diyl)bis(6-((2-(2-(2-aminoethoxy)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione), 6-[2-[2-(2-aminoethoxy)ethoxy]ethylamino]-2-[2-[2-[2-[6-[2-[2-(2-aminoethoxy)ethoxy]ethylamino]-1,3-dioxobenzo[de] [de]isoquinoline-2-yl]ethoxy]ethoxy]benzo[de]isoquinoline-1,3-dione, 2,2'-[1,2-ethylenediylbis(oxy-2,1-ethylenediyl)]bis[6-({2-[2-(2-aminoethoxy)ethoxy]ethyl}amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione], 1H-benzo[de]isoquinoline-1,3(2H)-dione, 2,2'-[1,2-ethylenediylbis(oxy-2,1-ethylenediyl)]bis[6-[[2-[2-(2-aminoethoxy)ethoxy]ethyl]amino]-(9Cl), N-5-azido -2-Nitrobenzoyloxysuccinimide, N-(β-maleimidepropoxy)succinimide ester, N-[e-maleiminoacetoxy]succinimide ester, N-[γ-maleimidebutyryloxy]succinimide, succinimide-6-(3-[2-pyridyldithio]propamido)acetate, m-maleamidobenzoyl-N-hydroxysuccinimide ester, 3-[2-pyridyldithio]propionylhydrazine, N-succinimide bromoacetate, N-succinimide iodoacetate, N-sulfosuccinimide iodoacetate, succinimide-4-[N-maleimidemethyl]cyclohexane At least one of the following: 1-hydroxy ester, N-succinimino-4-[4-maleiminophenyl]butyrate, succinimino-6-[β-maleiminopropamido]acetate, N-succinimino-3-[2-pyridyldithio]propionate, sulfosuccinimino-6-(3'-[2-pyridyldithio]propamido)hexanoate, m-maleiminobenzoyl-N-hydroxysulfosuccinimino ester, N-sulfosuccinimino-6-[4'-azido-2'-nitrophenylamino]hexanoate, and sulfosuccinimino-4-[N-maleiminomethyl]cyclohexane-1-carboxylic acid.

[0017] Optionally, the sustained-release material is at least one selected from liposomes, poly(lactic acid) microspheres, poly(caprolactone) microspheres, polyglycolic acid microspheres, starch-based microspheres, chitosan-based microspheres, gelatin-based microspheres, sodium alginate-based microspheres, polyvinyl alcohol-based microspheres, and polyurethane microcapsules. Liposomes are preferred.

[0018] Optionally, the coating is prepared by at least one of dip coating and spray coating.

[0019] Optionally, the coating may be any one of the following structures:

[0020] The coating includes at least one photosensitive layer and one auxiliary layer, wherein the raw material of the photosensitive layer includes a carrier and a photosensitizer dispersed in the carrier;

[0021] Alternatively, the coating may be a single layer, the raw materials of which include a carrier and photosensitizers and excipients dispersed in the carrier.

[0022] Optionally, the tube body has at least:

[0023] The guide wire cavities are respectively opened at both ends of the tube body;

[0024] The infusion chamber has one end open at the proximal end of the tube body and the other end connected to the interior of the balloon, and is used to inflate the balloon by injecting fluid.

[0025] The optical fiber assembly is inserted into the cavity, and the light-emitting portion is adjacent to the balloon.

[0026] Optionally, the tubing body includes multiple tubing bodies nested together, and the radial gap between the inner and outer tubing bodies is used to provide the guidewire cavity, the infusion cavity, and the receiving cavity, respectively.

[0027] Optionally, the tube body includes:

[0028] The inner tube provides the guidewire cavity inside;

[0029] An outer tube is fitted over the outer side of the inner tube, and the radial gap between the inner and outer tubes provides the injection cavity;

[0030] An extension tube is disposed in the radial gap between the inner tube and the outer tube, the cavity is provided inside the extension tube, and the distal end of the extension tube extends into the balloon and is fixed to the outer wall of the inner tube.

[0031] Optionally, the fiber optic assembly includes:

[0032] The light emitting device is externally mounted on the tube body;

[0033] The optical fiber has one end connected to the light emitting device and the other end inserted into the accommodating cavity and extends to the adjacent balloon, with the light-emitting part located at the other end.

[0034] Compared with existing technologies, this application loads photosensitizers and active drugs onto a balloon and encapsulates the active drug with a photoprotective sustained-release material to reduce the loss rate of the active drug due to light irradiation, thereby improving the therapeutic effect of the active drug. Attached Figure Description

[0035] Figure 1 This is a schematic diagram of the structure of a photodynamic balloon catheter system in one embodiment;

[0036] Figure 2 This is a schematic diagram of the photodynamic balloon catheter system in another embodiment;

[0037] Figure 3 This is a partial schematic diagram of the inner tube in one embodiment;

[0038] Figure 4 This is a schematic diagram of the fiber optic body fixing method in one embodiment.

[0039] The annotations in the figure are explained as follows:

[0040] 100. Tube body; 110. Proximal end; 120. Distal end; 130. Guidewire lumen; 140. Infusion lumen; 150. Receptacle lumen; 160. Inner tube; 161. Outer wall; 162. Groove; 170. Outer tube; 180. Extension tube;

[0041] 200. Balloon;

[0042] 300. Fiber optic assembly; 310. Optical emitting device; 320. Fiber optic body; 321. Light-emitting part. Detailed Implementation

[0043] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0044] It should be noted that when a component is said to be "connected" to another component, it can be directly connected to the other component or it can be connected to a component in between. When a component is said to be "set on" another component, it can be directly set on the other component or it may be set to a component in between.

[0045] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0046] See Figures 1-4An embodiment of this application provides a photodynamic balloon 200 catheter system, including a tube body 100, a balloon 200, and an optical fiber assembly 300; wherein the tube body 100 has a proximal end 110 and a distal end 120, the balloon 200 is fixed to the distal end 120 of the tube body 100, and the optical fiber assembly 300 is inserted into the tube body 100 and has a light-emitting portion 321 extending to the adjacent balloon 200. The surface of the balloon 200 is coated with excipients and photosensitizers, wherein the photosensitizers are activated at a light wavelength of 400-460 nm and crosslink the collagen and elastin of organs and / or tissues (e.g., blood vessels) to form a microscaffold in situ; the excipients include active drugs, which can be drugs for treating vascular diseases, such as at least one of paclitaxel, rapamycin, zotamolimus, tacrolimus, everolimus, tamsulolimus, zoromolimus, biolimus, docetaxel, protein-bound paclitaxel, and protein-bound dexamethasone. These drugs can be released into the blood vessels and / or onto the vessel walls through the balloon 200, where they are absorbed by cells.

[0047] The dosage of the active drug was determined based on the lesion condition. However, the experiment revealed that the expected therapeutic effect was not achieved after administration of the predetermined dosage. The study found that the reason was the rapid release of the active drug from the surface of the balloon 200 into the bloodstream, and the undesirable trend in the concentration change of the free active drug in the body, i.e., the decrease in the concentration of the free active drug was faster than the rate at which cells utilized the active drug. Further investigation revealed that the excessively rapid decrease in the concentration of the free active drug was due to its easy decomposition under light with a wavelength of 400-460 nm. When all the active drug was released into the bloodstream, some of the free active drug could not be absorbed by cells in time and was decomposed by light, leading to its inactivation. To solve this technical problem, the excipients also included a sustained-release material encapsulating the active drug, which protected the active drug, reduced its loss rate, and improved its utilization rate (Table 1).

[0048] The aforementioned sustained-release materials are generally microspheres or microcapsules, capable of effectively encapsulating active drugs. Specifically, they can be at least one of the following: liposomes, poly(lactic acid) based microspheres, polylactic acid based microspheres, polycaprolactone based microspheres, polyglycolic acid based microspheres, starch-based microspheres, chitosan-based microspheres, gelatin-based microspheres, sodium alginate-based microspheres, polyvinyl alcohol-based microspheres, and polyurethane microcapsules. Each microsphere can be prepared using an emulsion solvent evaporation method, with a particle size controlled between 0.095 and 15 μm. The microcapsules can be prepared using an in-situ polymerization method, with a particle size controlled between 0.2 and 10 μm.

[0049] In this application, the sustained-release material is preferably liposomes. Liposomes are hollow spheres composed of phospholipids and other lipid compounds. There are many specific types of liposomes. For example, depending on the raw materials used in synthesis, liposomes can be phospholipid-cholesterol liposomes, which have good biocompatibility and can be successfully endocytosed by cells, thereby smoothly transporting the active drug into the cell. Depending on the structure, liposomes can be single-compartment liposomes, multi-compartment liposomes, or multiphase liposomes. Depending on the performance, liposomes can be thermosensitive liposomes, pH-sensitive liposomes, ultrasound-sensitive liposomes, or magnetic liposomes. From the perspective of endocytosis, the particle size of the liposomes is required to be ≤5μm. The phospholipids used to prepare the liposomes can be soybean lecithin, egg yolk lecithin, dipalmitoylphosphatidylcholine, distearate phosphatidylcholine, etc., and the excipients (other lipid compounds) can be cholesterol, octadecylamine, phosphatidic acid, etc., with a mass ratio of phospholipids to excipients of 1:4 to 10.

[0050] The photosensitizers mentioned above can be porphyrins, porphyrin derivatives, phthalocyanines, chlorine, purines, 5-hydroxyacetic acid, 4-amino-1,8-naphthylimide, 1,8-naphthylimide, 1,8-naphthylimide polymers, dinaphthylimide compounds, 2,2'-((ethane-1,2-di(oxy))bis(ethane-2,1-diyl)bis(6-((2-(2-(2-(2-aminoethoxy)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione), 6-[2-[2-(2-aminoethoxy)ethoxy]ethylamino]-2-[2-[2-[2-[6-[2-[2-(2-aminoethoxy)ethyl]ethylamino] [Oxy]ethylamino]-1,3-dioxobenzo[de]isoquinoline-2-yl]ethoxy]ethoxy]benzo[de]isoquinoline-1,3-dione, 2,2'-[1,2-ethylenediylbis(oxy-2,1-ethylenediyl)]bis[6-({2-[2-(2-aminoethoxy)ethoxy]ethyl}amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione], and 1H-benzo[de]isoquinoline-1,3(2H)-dione, 2,2'-[1,2-ethylenediylbis(oxy-2,1-ethylenediyl)]bis[6-[[2-[2-(2-aminoethoxy)ethoxy]ethyl]amino]-( 9Cl), N-5-azido-2-nitrobenzoyloxysuccinimide, N-(β-maleimidepropoxy)succinimide ester, N-[e-maleiminoacetoxy]succinimide ester, N-[γ-maleimidebutyryloxy]succinimide, succinimino-6-(3-[2-pyridyldithio]propamido)acetate, m-maleamidobenzoyl-N-hydroxysuccinimide ester, 3-[2-pyridyldithio]propionylhydrazine, N-succiniminobromoacetate, N-succiniminoiodoacetate, N-sulfosucciniminoiodoacetate, succinimino-4-[N-maleimino] At least one of the following: [methyl]cyclohexane-1-hydroxy ester, N-succinimino-4-[4-maleiminophenyl]butyrate, succinimino-6-[β-maleiminopropamido]acetate, N-succinimino-3-[2-pyridyldithio]propionate, sulfosuccinimino-6-(3'-[2-pyridyldithio]propamido)hexanoate, m-maleiminobenzoyl-N-hydroxysulfosuccinimino ester, N-sulfosuccinimino-6-[4'-azido-2'-nitrophenylamino]hexanoate, and sulfosuccinimino-4-[N-maleiminomethyl]cyclohexane-1-carboxylic acid.

[0051] Preferably, it is 2,2'-((ethane-1,2-di(oxy))di(ethane-2,1-diyl)di(6-((2-(2-(2-aminoethoxy)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione), also known as 10-8-10 dimer.

[0052] To ensure the coating's light-protection and sustained-release effects, the mass ratio of the active drug to the sustained-release material in the above excipients is 1:1 to 20, preferably 1:10.

[0053] The mass ratio of the photosensitizer to the active drug is 1:0.3 to 1:1. This mass ratio can effectively dilate blood vessels while reducing the mutual coverage of the photosensitizer and the active drug liposomes, allowing both to effectively diffuse into the blood vessel wall. Preferably, the mass ratio is 1:0.5, which results in a faster diffusion rate during use.

[0054] In one embodiment, the coating includes at least one photosensitive layer and one excipient layer, wherein the raw materials of the photosensitive layer include a carrier and a photosensitizer dispersed in the carrier, and the carrier may be shellac, etc. The order of the layers on the surface of the balloon 200 is not limited. The coating can be prepared by:

[0055] Prepare solutions containing a carrier and a photosensitizer, as well as solutions containing excipients;

[0056] Each solution is applied sequentially to the surface of the balloon 200 to form a coating; the order in which the solutions are applied to the surface of the balloon 200 is not restricted.

[0057] In another embodiment, the coating is a single layer, and its raw materials include a carrier and photosensitizers and excipients dispersed on the carrier. The carrier can be shellac, etc. The preparation method of the coating is as follows:

[0058] Prepare solutions containing photosensitizers and provide excipients;

[0059] A solution containing photosensitizer and excipients is dispersed in a carrier, and the resulting mixture is applied to the surface of the balloon 200.

[0060] All raw materials used in the following embodiments or comparative examples are commercially available.

[0061] Example 1

[0062] The coating preparation method is as follows:

[0063] Dissolve 100 mg of 10-8-10 dimer in 5 mL of a mixture of ethanol and acetic acid (volume ratio of ethanol to acetic acid is 24:1) to obtain 10-8-10 oxalate solution A.

[0064] Dissolve 100 mg of shellac in 5 mL of ethanol to obtain solution B;

[0065] After mixing A and B, 10 mL of solution C is obtained;

[0066] C is sprayed onto the surface of balloon 200 and dried to obtain balloon 200 with coating I;

[0067] Dissolve 0.025g of soybean lecithin, 0.2g of cholesterol, and 50mg of paclitaxel in 5mL of chloroform to obtain an excipient solution;

[0068] The excipient solution is sprayed onto the balloon 200 with coating I and dried to obtain the photodynamic balloon 200.

[0069] The liposomes have a particle size distribution of approximately 400–1000 nm, with an average of 700 nm and an encapsulation efficiency of 85%.

[0070] Encapsulation rate % = (W 总 -W 游离 ) / W 总 x100%

[0071] Among them W 总 W represents the total amount of drug in the suspension within the liposomes. 游离 This refers to the amount of drug not encapsulated in liposomes.

[0072] Example 2

[0073] The coating preparation method is as follows:

[0074] Dissolve 0.025g of soybean lecithin, 0.2g of cholesterol, and 50mg of paclitaxel in 5mL of chloroform to obtain an excipient solution; spray the excipient solution onto the balloon 200 and air dry to obtain a balloon 200 with coating I;

[0075] Dissolve 100 mg of 10-8-10 dimer in 5 mL of a mixture of ethanol and acetic acid (volume ratio of ethanol to acetic acid is 24:1) to obtain 10-8-10 oxalate solution A;

[0076] Dissolve 100 mg of shellac in 5 mL of ethanol to obtain solution B;

[0077] After mixing A and B, 10 mL of solution C is obtained;

[0078] C is sprayed onto the surface of the balloon 200 with coating I and dried to obtain the photodynamic balloon 200.

[0079] The liposomes have a particle size distribution of approximately 200–1000 nm, with an average of 500 nm, and an encapsulation efficiency of 81%.

[0080] Example 3

[0081] The coating preparation method is as follows:

[0082] Dissolving the 10-8-10 dimer in a mixture of ethanol and acetic acid yields a 10-8-10 oxalate solution A.

[0083] Take 0.025g of soybean lecithin and 0.2g of cholesterol, dissolve them in chloroform, heat to 50℃ to make the chloroform evaporate and form a liposome precursor membrane, then add 10mL of water and 50mg of paclitaxel mixture to obtain a liposome suspension, centrifuge, freeze dry to obtain solid paclitaxel-containing liposome B;

[0084] Shellac was dissolved in ethanol, and then 5 mL of 20 mg / mL 10⁻⁸⁻¹⁰ oxalate solution A and 275 mg of paclitaxel-containing liposome B were added. The mixture was then sprayed onto the surface of the capsule 200 and allowed to air dry.

[0085] The liposomes have a particle size distribution of approximately 830–1450 nm, with an average of 1207 nm and an encapsulation efficiency of 63%.

[0086] Example 4

[0087] Following the method of Example 1, rapamycin was encapsulated in liposomes to prepare photodynamic balloon 200.

[0088] Comparative Example 1

[0089] Dissolve 100 mg of 10-8-10 dimer in 5 mL of a mixture of ethanol and acetic acid to obtain 10-8-10 oxalate solution A;

[0090] Disperse 50 mg of paclitaxel into solution A to obtain solution B;

[0091] Dissolve shellac in ethanol, then add solution B, mix well, spray onto the surface of the spherical capsule 200, and let it dry.

[0092] Comparative Example 2

[0093] Dissolve 100 mg of 10-8-10 dimer in 5 mL of a mixture of ethanol and acetic acid to obtain 10-8-10 oxalate solution A;

[0094] Disperse 50 mg of rapamycin into solution A to obtain solution B;

[0095] Dissolve shellac in ethanol, then add solution B, mix well, spray onto the surface of the spherical capsule 200, and let it dry.

[0096] Test case

[0097] The balloons prepared in Examples 1 and 4, as well as Comparative Examples 1 and 2, were subjected to light irradiation tests. The degradation of paclitaxel and rapamycin over time was monitored using high-performance liquid chromatography. The test results are shown in Table 1.

[0098] Table 1 Degradation status of active pharmaceutical ingredients

[0099]

[0100] As shown in Table 1, paclitaxel and rapamycin exhibited a degradation rate of over 20% after irradiation with light at a wavelength of 400-460 nm for 1 minute, and the degradation rate increased synchronously with the extension of time, reaching over 80% degradation at 10080 (7 days). However, after encapsulation with slow-release materials, the degradation rate was significantly reduced, with the degradation rate of paclitaxel decreasing to 3% after irradiation for 1 minute.

[0101] The aforementioned tube 100 can be a multi-lumen tube. For example, in one embodiment, the tube 100 has at least a guidewire lumen 130, an infusion lumen 140, and a receiving lumen 150. The guidewire lumen 130 is open at both ends of the tube 100 for the guidewire to pass through. One end of the infusion lumen 140 is open at the proximal end 110 of the tube 100, and the other end communicates with the interior of the balloon 200. Fluid can be infused into the infusion lumen 140 to drive the balloon 200 to inflate. After inflation, the coating on the surface of the balloon 200 can be rapidly released. The optical fiber assembly 300 is inserted into the receiving lumen 150, and its light-emitting portion 321 is adjacent to the balloon 200. This proximity mainly emphasizes that the light emitted by the optical fiber assembly 300 acts on the balloon 200 at a small distance, which can ensure the range and intensity of illumination. This allows the photosensitizer to cross-link with the collagen fibers of the blood vessel wall to form a vascular microscaffold with a certain supporting capacity, ensuring that the blood vessel wall can remain in an expanded state after the balloon 200 is withdrawn.

[0102] The tube body 100 may include multiple tubes nested together, and the radial gaps inside each tube and / or between the inner and outer tubes 170 are used to provide the guide wire cavity 130, the injection cavity 140 and the receiving cavity 150 respectively. The guide wire cavity 130 and the receiving cavity 150 may be combined into one or exist separately.

[0103] For example, in one embodiment, the multiple tubes include an inner tube 160 and an outer tube 170, wherein the inner tube 160 provides a guide wire lumen 130, the gap between the inner tube 160 and the outer tube 170 provides an infusion cavity 140, and the receiving cavity 150 is provided by an independent tube or shares the gap between the inner tube 160 and the outer tube 170, wherein the independent tube is located in the gap between the inner tube 160 and the outer tube 170.

[0104] See Figure 2 The accommodating cavity 150 is provided by an extension tube 180 located in the radial gap between the inner tube 160 and the outer tube 170, the distal end 120 of the extension tube 180 extending into the balloon 200 and fixed to the outer wall of the inner tube 160.

[0105] The aforementioned balloon 200 can be made of materials such as polyvinyl chloride (PVC), polyethylene (PE), polyurethane (PU), nylon (PA), and polyethylene terephthalate (PET).

[0106] The outer tube 170, inner tube 160 and extension tube 180 mentioned above may be composed of one or more of polyvinyl chloride (PVC), polyimide (PI), nylon (PA), block polyether amide resin (PBEX), polyethylene (PE), and thermoplastic polyurethane elastomer rubber (TPU).

[0107] The optical fiber assembly 300 includes an optical emitting device 310 and an optical fiber body 320. The optical emitting device 310 is external to the tube body 100. One end (proximal end 110) of the optical fiber body 320 is connected to the optical emitting device 310, and the other end (distal end 120) is inserted into the receiving cavity 150 and extends to the adjacent balloon 200. The light-emitting part 321 is located at this end.

[0108] The optical fiber body 320 can be movably placed inside the tube 100 or fixed inside the tube 100. Its fixing position can be adjusted according to the specific structure of the tube 100, and the fixing method can be adhesive bonding or welding. For example, when the accommodating cavity 150 shares the gap between the inner tube 160 and the outer tube 170, the distal end 120 of the aforementioned optical fiber body 320 can be fixed to the outer wall 161 of the inner tube 160 or the inner wall of the outer tube 170. Figure 1 If the accommodating cavity 150 is provided by the extension tube 180, the portion of the distal end 120 of the optical fiber body 320 extending out of the accommodating cavity 150 is fixed to the outer wall of the inner tube 160. Figure 2 ).

[0109] For easy fixing of the distal end 120 of the optical fiber body 320, see [reference needed]. Figure 3 , 4 The outer wall 161 of the inner tube 160 is provided with a groove 162. The depth of the groove 162 can be set according to the diameter of the optical fiber body 320. For example, in one embodiment, the depth of the groove 162 is 0.01 to 0.3 mm.

[0110] This application releases photosensitizers and active drugs through a photodynamic balloon 200 catheter system, and encapsulates the active drug with a photoprotective sustained-release material to reduce the loss rate of free active drugs in vivo due to light irradiation, improve the utilization rate of active drugs, and thus ensure the efficacy of active drugs.

[0111] The technical features of the embodiments described above can be combined arbitrarily. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as the combination of these technical features does not contradict each other, it should be considered to be within the scope of this specification. When technical features of different embodiments are embodied in the same drawing, it can be regarded as the drawing also disclosing examples of combinations of the various embodiments involved.

[0112] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this application should be determined by the appended claims.

Claims

1. A photodynamic balloon catheter system, characterized in that, include: The tube body has a relatively proximal end and a distal end; A balloon, the balloon being fixed to the distal end of the tube; An optical fiber assembly is inserted into the tube and has a light-emitting portion extending to the vicinity of the balloon; The surface of the balloon is coated with excipients and photosensitizers; The photosensitizer can activate collagen and elastin to crosslink when irradiated by light with a wavelength of 400-460nm emitted from the luminescent site. The excipients include an active pharmaceutical ingredient and a sustained-release material encapsulating the active pharmaceutical ingredient, wherein the active pharmaceutical ingredient is at least one of paclitaxel, rapamycin, zotamolimus, tacrolimus, everolimus, tamsulolimus, zoromolimus, biolimus, docetaxel, protein-bound paclitaxel, and protein-bound dexamethasone. The sustained-release material has a photoprotective effect against light irradiation in vivo, and has a microsphere or microcapsule structure, which can effectively encapsulate the active drug. The sustained-release material is a liposome, which is a hollow sphere composed of phospholipids and additives belonging to lipid compounds; The phospholipid is selected from soybean lecithin, egg yolk lecithin, dipalmitoylphosphatidylcholine or distearate phosphatidylcholine, and the excipient is selected from cholesterol, octadecylamine or phosphatidic acid; The mass ratio of the phospholipid to the additive is 1:4~10.

2. The photodynamic balloon catheter system according to claim 1, characterized in that, The liposomes have a particle size of 0.095~5μm.

3. The photodynamic balloon catheter system according to claim 1, characterized in that, In the excipients, the mass ratio of the active drug to the sustained-release material is 1:1 to 20.

4. The photodynamic balloon catheter system according to claim 1, characterized in that, The mass ratio of the photosensitizer to the active drug is 1:0.2~5.

5. The photodynamic balloon catheter system according to claim 1, characterized in that, The photosensitizer is porphyrin, porphyrin derivatives, phthalocyanine, chlorine, purine, 5-hydroxyacetic acid, 4-amino-1,8-naphthylimide, 1,8-naphthylimide, 1,8-naphthylimide polymer, dinaphthylimide compound, 2,2'-((ethane-1,2-di(oxy))bis(ethane-2,1-diyl)bis(6-((2-(2-(2-aminoethoxy)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione), 6-[2-[2-(2-aminoethoxy)ethoxy]ethylamino]-2-[2-[2-[2-[6-[2-[2-(2-aminoethoxy)ethoxy]ethoxy] [2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethyl]benzo[[9C]]-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethyl]amino]benzo[[2- ... l), N-5-azido-2-nitrobenzoyloxysuccinimide, N-(β-maleimidepropoxy)succinimide ester, N-[e-maleiminoacetoxy]succinimide ester, N-[γ-maleimidebutyryloxy]succinimide, succinimide-6-(3-[2-pyridyldithio]propamido)acetate, m-maleamidobenzoyl-N-hydroxysuccinimide ester, 3-[2-pyridyldithio]propionylhydrazine, N-succinimide bromoacetate, N-succinimide iodoacetate, N-sulfosuccinimide iodoacetate, succinimide-4-[N-maleimidemethyl] The following is a list of at least one of the following: cyclohexane-1-hydroxy ester, N-succinimino-4-[4-maleiminophenyl]butyrate, succinimino-6-[β-maleiminopropamido]acetate, N-succinimino-3-[2-pyridyldithio]propionate, sulfosuccinimino-6-(3'-[2-pyridyldithio]propamido)hexanoate, m-maleiminobenzoyl-N-hydroxysulfosuccinimino ester, N-sulfosuccinimino-6-[4'-azido-2'-nitrophenylamino]hexanoate, and sulfosuccinimino-4-[N-maleiminomethyl]cyclohexane-1-carboxylic acid.

6. The photodynamic balloon catheter system according to claim 1, characterized in that, The coating has any of the following structures: The coating includes at least one photosensitive layer and one auxiliary layer, wherein the raw material of the photosensitive layer includes a carrier and a photosensitizer dispersed in the carrier; Alternatively, the coating may be a single layer, the raw materials of which include a carrier and photosensitizers and excipients dispersed in the carrier.

7. The photodynamic balloon catheter system according to claim 6, wherein the carrier is shellac.

8. The photodynamic balloon catheter system according to claim 1, characterized in that, The tube body has at least: The guide wire cavities are respectively opened at both ends of the tube body; The infusion chamber has one end open at the proximal end of the tube body and the other end connected to the interior of the balloon, and is used to inflate the balloon by injecting fluid. The optical fiber assembly is inserted into the cavity, and the light-emitting portion is adjacent to the balloon.

9. The photodynamic balloon catheter system according to claim 8, characterized in that, The tubing body includes multiple interlocking tubing components, with the radial gaps between the inner and outer tubing components serving to provide the guide wire cavity, injection cavity, and receiving cavity, respectively.

10. The photodynamic balloon catheter system according to claim 9, characterized in that, The tube body includes: The inner tube provides the guidewire cavity inside; An outer tube is fitted over the outer side of the inner tube, and the radial gap between the inner and outer tubes provides the injection cavity; An extension tube is disposed in the radial gap between the inner tube and the outer tube, the cavity is provided inside the extension tube, and the distal end of the extension tube extends into the balloon and is fixed to the outer wall of the inner tube.

11. The photodynamic balloon catheter system according to claim 10, characterized in that, The optical fiber assembly includes: The light emitting device is externally mounted on the tube body; The optical fiber has one end connected to the light emitting device and the other end inserted into the accommodating cavity and extends to the adjacent balloon, with the light-emitting part located at the other end.

Images