Medical device and system, method of manufacture

Abstract

The present application provides a medical device and system, a preparation method, the medical device comprises a base body and a coating, the base body can expand or contract along its radial direction; the coating is arranged on at least part of the outer surface of the base body, and the coating comprises a protein and a cross-linking agent. The base body can be a balloon body, after being introduced into a lesion blood vessel, the protein can be cross-linked with the protein on the blood vessel wall under the action of the cross-linking agent, to form a “protein micro-scaffold” in situ to support the blood vessel wall, maintain the blood vessel gain, maintain the expanded size of the blood vessel, and reduce the possibility of blood vessel restenosis.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, specifically relating to a medical device and system, and its preparation method. Background Technology

[0002] Atherosclerosis refers to the thickening of the walls and narrowing of the lumens of arteries that supply blood to various organs such as the heart, brain, and kidneys. It is a major cause of heart attacks and strokes. Currently, there are many ways to treat atherosclerosis, including balloon angioplasty, stent implantation, and plaque resection. Among these, stent implantation is the most common treatment. However, as a long-term implanted device, stent implantation still faces the risks of long-term restenosis and thrombosis.

[0003] The advent of biodegradable stents has addressed the risks of long-term implants, but they are still considered foreign implants. Therefore, patients need to take medication continuously in the early stages after implantation. Furthermore, the degradation of the synthetic materials used in biodegradable stents can lead to an acidic vascular matrix, increasing the risk of inflammation and calcification. Drug-eluting balloons are another treatment option. While they eliminate the problem of foreign body implantation, drug delivery relies solely on physically adhering the drug coating to the vessel wall. Without vascular support, the drug is easily lost, making it difficult to maintain drug concentrations for extended periods, resulting in poor treatment efficacy and the inability to maintain long-term luminal gain. Percutaneous transluminal angioplasty (PTA) is another treatment method commonly used for patients with peripheral artery disease (PAD), but its effectiveness is not ideal due to vascular retraction and dissection. Summary of the Invention

[0004] The purpose of this invention is to provide a medical device and system, and a preparation method, aimed at better treating atherosclerosis.

[0005] To achieve the above objectives, the present invention provides a medical device comprising a substrate and a coating, the substrate being capable of expanding or contracting radially therein; the coating being disposed on at least a portion of the outer surface of the substrate, and the coating comprising a protein and a crosslinking agent.

[0006] Optionally, the crosslinking agent includes a photosensitive crosslinking agent, which undergoes a crosslinking reaction with the protein under light irradiation.

[0007] Optionally, the photosensitive crosslinking agent includes at least one of methylene blue, methylene green, rose red, riboflavin, proflavin, fluorescein, eosin, 4-amino-1,8-naphthylimide, 2,2'-((ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(6-((2-(2-(2-(2-aminoethoxy)ethoxy)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione) and its salts.

[0008] Optionally, the crosslinking agent includes a non-photosensitive crosslinking agent, and the coating further includes an isolator that isolates the protein from the non-photosensitive crosslinking agent to prevent the protein from undergoing a crosslinking reaction with the non-photosensitive crosslinking agent.

[0009] Optionally, the non-photosensitive crosslinking agent includes physical crosslinking agents and / or chemical crosslinking agents, wherein the chemical crosslinking agent includes at least one of glutaraldehyde, polyepoxide, genipin, horseradish catalase, ammonium persulfate, terpyridine ruthenium chloride, camphorquinone, and curcumin.

[0010] Optionally, the physical crosslinking agent includes at least one of tannic acid, pentagalloglucoside, gallic acid ester, gallic acid, ellagic acid, proanthocyanidins, anthocyanins, quercetin, luteolin, catechin, and epicatechin.

[0011] Optionally, the protein includes at least one of humanized elastin, humanized collagen, human serum albumin, silk fibroin, and proteoglycan.

[0012] Optionally, the mass ratio of the protein to the cross-linking agent is 100:1 to 1:1.

[0013] Optionally, the substrate includes a main body; the coating is disposed on at least a portion of the outer surface of the main body.

[0014] Optionally, the coating covers the entire outer surface of the main body.

[0015] Optionally, the coating includes a plurality of sub-coatings, which are arranged at axial intervals along the main body.

[0016] Optionally, the coating is a spiral structure surrounding the axis of the main body.

[0017] Optionally, the coating has a mesh structure.

[0018] Optionally, the coating may also include a drug.

[0019] Optionally, the matrix includes a balloon or a stent.

[0020] To achieve the above objectives, the present invention also provides a medical system comprising the medical device and catheter body as described above, wherein the base is sleeved on the distal outer peripheral surface of the catheter body.

[0021] Optionally, the crosslinking agent includes a photosensitive crosslinking agent; the medical system further includes an optical fiber assembly, which is at least partially inserted into the catheter body, the optical fiber assembly including a light-emitting portion extending to the distal end of the catheter body, and the position of the light-emitting portion corresponding to the position of the substrate; the distal end of the catheter body is configured to allow light emitted by the light-emitting portion to irradiate the substrate.

[0022] Optionally, the light transmittance of the distal end of the catheter is greater than 90%.

[0023] To achieve the above objectives, the present invention also provides a preparation method for preparing the medical device as described above, the preparation method comprising the following steps:

[0024] The substrate and coating solution are provided, the coating solution comprising a protein and a crosslinking agent;

[0025] The coating solution is applied to at least a portion of the outer surface of the substrate;

[0026] The coating solution is dried to form the coating.

[0027] Compared with the prior art, the medical device and system and the preparation method of the present invention have the following advantages:

[0028] The aforementioned medical device includes a substrate and a coating. The substrate is capable of expanding or contracting radially. The coating is disposed on at least a portion of the outer surface of the substrate and comprises proteins and a cross-linking agent. The substrate, for example, is a balloon or stent that can be inserted into a human organ, such as a blood vessel. The proteins in the coating can permeate into the blood vessel wall, and under the action of the cross-linking agent, these exogenous proteins can undergo a cross-linking reaction with collagen and elastin on the blood vessel wall to form a mesh-like cross-linked structure. This cross-linked structure has good mechanical properties and can serve as an in-situ "protein microscaffold" to support the blood vessel, fix the size of the blood vessel after expansion, and prevent severe rebound of the blood vessel when the substrate is withdrawn, thereby reducing the probability of intravascular restenosis. Attached Figure Description

[0029] The accompanying drawings are provided to better understand the invention and are not intended to unduly limit the scope of the invention. Wherein:

[0030] Figure 1 This is a schematic diagram of the structure of a medical balloon catheter provided according to an embodiment of the present invention;

[0031] Figure 2 This is a partial structural schematic diagram of a medical balloon catheter provided according to an embodiment of the present invention, in which the coating covers the entire outer surface of the main body of the balloon body;

[0032] Figure 3 This is a partial structural schematic diagram of a medical balloon catheter provided according to an embodiment of the present invention. The coating in the diagram includes multiple sub-coatings spaced apart along the axial direction of the main body.

[0033] Figure 4 This is a partial structural schematic diagram of a medical balloon catheter provided according to an embodiment of the present invention, wherein the coating in the diagram has a mesh-like structure;

[0034] Figure 5 This is a schematic diagram of a coating applied to the balloon body of a medical balloon catheter according to an embodiment of the present invention;

[0035] Figure 6 yes Figure 1 The image shows an AA cross-sectional view of a medical balloon catheter.

[0036] Figure 7 This is a partial structural schematic diagram of the optical fiber assembly of a medical balloon catheter according to an embodiment of the present invention;

[0037] Figure 8 This is a schematic diagram comparing the cross-sectional dimensions of blood vessels after the medical balloon catheters provided in Embodiment 1, Comparative Example 1, and Comparative Example 2 of the present invention are applied. In the diagram, a is a blood vessel using the medical balloon catheter provided in Comparative Example 1, b is a blood vessel using the medical balloon catheter provided in Comparative Example 2, c is a blood vessel using the medical balloon provided in Embodiment 1, and d is a blood vessel using the medical balloon catheter provided in Comparative Example 3.

[0038] Figure 9 These are photographs of the cross-sections of blood vessels using medical catheters provided in Comparative Example 1, Comparative Example 2, and Example 1 after staining. In the figures, a is a blood vessel using the medical balloon catheter provided in Comparative Example 1, b is a blood vessel using the medical balloon catheter provided in Comparative Example 2, c is a blood vessel using the medical balloon catheter provided in Example 1, and d is a blood vessel using the medical balloon catheter provided in Comparative Example 3.

[0039] [The annotations in the attached figures are explained below]:

[0040] 100-Catheter body, 110-Inner tube, 111-Guidewire lumen, 120-Outer tube, 200-Medical balloon, 210-Balloon body, 211-Main body, 212-Connection, 220-Coating, 221-Sub-coating, 300-Fiber optic assembly, 310-Light emitting part, 311-Fiber optic core, 312-Scattering layer, 320-Protective layer, 400-Connector, 410-First interface, 412-Second interface, 500-Guiding head, 600-Illuminating element;

[0041] 10 - Nozzle, 20 - Mandrel. Detailed Implementation

[0042] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that the illustrations provided in this embodiment are only schematic representations of the basic concept of the present invention. Therefore, the drawings only show components related to the present invention and are not drawn according to the actual number, shape, and size of components in the actual implementation. In the actual implementation, the type, quantity, and proportion of each component can be arbitrarily changed, and the component layout may also be more complex.

[0043] Furthermore, while each embodiment described below possesses one or more technical features, this does not imply that users of the present invention must simultaneously implement all technical features in any embodiment, or can only separately implement some or all technical features in different embodiments. In other words, provided it is feasible, those skilled in the art can, based on the disclosure of the present invention and depending on design specifications or implementation requirements, selectively implement some or all technical features in any embodiment, or selectively implement a combination of some or all technical features in multiple embodiments, thereby increasing the flexibility in implementing the present invention.

[0044] In this article, the terms “proximal” and “distal” refer to the relative orientation, position, and direction of the components or movements relative to each other from the perspective of the physician using the medical device. Although “proximal” and “distal” are not restrictive, “proximal” usually refers to the end of the medical device that is closer to the physician during normal operation, while “distal” usually refers to the end that first enters the patient’s body.

[0045] The purpose of this invention is to provide a medical system in which, after the substrate of the medical device is introduced into the human body and expanded, a "protein microscaffold" can be formed in situ on the blood vessel wall. The "protein microscaffold" is used to support the blood vessel to maintain the blood vessel expansion size as much as possible and avoid the problem of blood vessel restenosis caused by severe rebound.

[0046] To make the objectives, advantages, and features of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings. It should be noted that the drawings are all in a very simplified form and use non-precise proportions, and are only used to facilitate and clearly illustrate the objectives of the embodiments of the present invention. The same or similar reference numerals in the drawings represent the same or similar parts.

[0047] The medical system includes a medical device, which includes a base capable of expanding or contracting radially therein. Typically, the base is, for example, a balloon body 210 (e.g., Figure 1 (as shown) or a stent. When the substrate is the balloon body, the medical device is a medical balloon, and the medical system can be a medical balloon catheter. The following description uses a medical balloon catheter as an example. Those skilled in the art can modify the following description to adapt it to situations where the substrate is a stent or other medical device capable of supporting a coating.

[0048] Figure 1 A schematic diagram of the structure of the medical balloon catheter is shown. Figure 1 As shown, the medical balloon catheter includes a catheter body 100 and a medical balloon 200, with a filling agent flow channel formed on the catheter body 100. The medical balloon 200 includes a balloon body 210 and a coating 220, with the balloon body 210 sleeved on the distal outer peripheral surface of the catheter body 100. The balloon body 210 has an inflation cavity communicating with the filling agent flow channel. The coating 220 is disposed on at least a portion of the outer surface of the balloon body 210, and the coating 220 includes a protein and a cross-linking agent, wherein the protein is used to cross-link with proteins on the blood vessel wall under the action of the cross-linking agent.

[0049] The medical balloon catheter described herein can be used to treat atherosclerosis. In practical application, the medical balloon 200 is inserted into the diseased blood vessel in the human body. Filling agent is infused into the filling cavity of the balloon body 210 through the filling agent channel, causing the balloon body 210 to expand. This allows the coating 220 on the outer surface of the balloon body 210 to come into close contact with the blood vessel wall. The proteins within the coating 220, as exogenous proteins, can penetrate into the blood vessel wall after a short release of approximately 30-60 seconds, resulting in a high protein concentration at the site of contact between the blood vessel wall and the coating 220. Those skilled in the art know that the blood vessel wall includes the intima, media, and adventitia. The intima is lined with squamous endothelial cells, the media is separated from the intima by internal elastic lamina, and the media is composed of alternating layers of elasticity, elastic fibers, and smooth muscle cells. The adventitia is composed of collagen and elastic fibers. In other words, the blood vessel wall contains elastin and extracellular matrix proteins. Proteins can undergo cross-linking reactions to form a mesh-like structure with certain mechanical properties and the ability to be stretched. In other words, in this embodiment of the invention, the elastin and extracellular matrix proteins on the blood vessel wall can be fully cross-linked with the exogenous proteins from the coating 220 under the action of the cross-linking agent to form a mesh-like cross-linked structure. This cross-linked structure forms an in-situ "protein microscaffold." The "protein microscaffold" has good mechanical properties and can support the blood vessel after it has been expanded by the medical balloon 200, maintaining the expanded blood vessel size to a certain extent, avoiding vascular rebound caused by the retraction of the balloon 210, maintaining lumen gain, reducing or even avoiding vascular restenosis, and achieving the purpose of vascular remodeling. Moreover, this "protein microscaffold" does not degrade and there is no problem of foreign implant residue.

[0050] In this embodiment of the invention, the introduction of exogenous proteins through the coating 220 can increase the protein concentration in the area where the blood vessel wall contacts the coating 220, forming more cross-linking products, improving the mechanical properties of the formed "protein microscaffold", and effectively avoiding the problem that the cross-linking reaction cannot occur or the degree of cross-linking is insufficient due to insufficient protein content in the blood vessel wall or insufficient protein distribution in certain parts, thus preventing the "protein microscaffold" from effectively supporting the blood vessel wall.

[0051] Furthermore, since the coating 220 is an artificially created coating, it can be formed in a predetermined shape on the outer surface of the balloon body 210 during the production stage according to actual needs. This allows for the adjustment of protein concentrations at different locations on the blood vessel wall after the medical balloon 200 is implanted into a blood vessel. Typically, the protein concentration is higher at the locations on the blood vessel wall in contact with the coating 220, and lower at the locations on the blood vessel wall not in contact with the coating 220.

[0052] Specifically, such as Figure 1 As shown, the balloon body 210 includes a main body 211 and two connecting portions 212 respectively connected to the axial ends of the main body 211. The coating 220 is disposed on at least a portion of the outer surface of the main body 211. It should be noted that when the substrate is a support, the support only includes the main body and does not include the connecting portions.

[0053] More specifically, in some embodiments, such as Figure 2 As shown, the coating 220 covers the entire outer surface of the main body 211, such that the portion of the blood vessel wall corresponding to the main body 211 is entirely in contact with the coating 220 and receives exogenous proteins from the coating 220, resulting in a high protein concentration. In other embodiments, such as Figure 3 As shown, the coating 220 includes a plurality of sub-coatings 221 spaced apart axially along the main body 211. In this case, the portion of the blood vessel wall in contact with each sub-coating 221 receives exogenous proteins from the coating 220 and has a higher protein concentration, while the portion of the blood vessel wall corresponding to the area between two adjacent sub-coatings 221 has a relatively lower protein concentration because it is not in contact with the coating 220. In other embodiments, such as Figure 4 As shown, the coating 220 has a mesh-like structure, and the portion of the blood vessel wall corresponding to the mesh area does not contact the coating 220 and thus has a relatively low protein concentration. In some other embodiments, the coating 220 is a helical structure surrounding the main body 211, and the portion of the blood vessel wall corresponding to the area between two helical turns of the helical structure does not contact the coating 220 and thus has a relatively low protein concentration. Applying the coating 220 to different areas of the outer surface of the main body 211 allows for different mechanical properties in the resulting vascular microstent.

[0054] The coating 220 is formed by drying a coating solution attached to the main body 211 of the balloon 210. The coating 220 solution includes the protein and the crosslinking agent, which are dissolved in a solvent under ultrasonication. The solvent includes, but is not limited to, at least one of ethanol, ethyl acetate, acetone, tetrahydrofuran, and water.

[0055] In this embodiment of the invention, the coating solution can be applied to the spherical body 210 in any suitable manner as needed. In a typical embodiment, a single-nozzle printing method, such as ultrasonic spraying, can be used. Specifically, as shown... Figure 5As shown, before spraying, the balloon body 210 is first fitted onto a mandrel 20 located below the nozzle 10. Then, the mandrel 20 is controlled to rotate to drive the balloon body 210 to rotate synchronously, and the nozzle 10 is also controlled to move along the axial direction of the balloon body 210 and spray the coating solution for printing. It can be understood that the entire printing process can be controlled by a computer, and the rotation speed of the mandrel 20, the moving speed of the nozzle 10, and the spraying speed of the nozzle 10 can be preset by programming, so that the coating solution is sprayed onto the main body 211 along the preset path, so that the coating solution can adhere to the entire outer surface of the main body 211, or form multiple rings spaced apart along the axial direction of the main body 211 on the outer surface of the main body 211, or form a mesh structure or a spiral structure on the main body 211. In other words, different program settings can be made according to actual needs to form coatings 220 with different patterns on the main body 211, and finally obtain vascular micro-stents with different mechanical properties on the blood vessel wall.

[0056] Of course, in other implementations, the coating solution can also be directly applied to the main body 211 of the balloon body 210 by dip coating.

[0057] The proteins used in the embodiments of this invention include, but are not limited to, at least one of humanized elastin, humanized collagen, human serum albumin, silk fibroin, and proteoglycans. Silk fibroin, as a natural protein macromolecule, possesses excellent biocompatibility and degradability, as well as an ordered molecular structure and good mechanical properties. When forming a network-like cross-linked structure, it allows for better orientation of the cross-linked structure and superior mechanical properties. Therefore, in the embodiments of this invention, the proteins preferably include silk fibroin.

[0058] Optionally, the crosslinking agent includes a photosensitive crosslinking agent. The term "photosensitive crosslinking agent" refers to an agent capable of undergoing a crosslinking reaction with proteins under light irradiation. In other words, the crosslinking agent functions as both a crosslinking agent and a photosensitizer, activating under light irradiation to generate free radicals, thereby initiating the crosslinking reaction.

[0059] Alternatively, the crosslinking agent includes a non-photosensitive crosslinking agent, which means that the crosslinking agent can directly crosslink with the protein without light exposure. In this embodiment of the invention, the protein and the crosslinking agent are intended to crosslink on the blood vessel wall, rather than in vitro. To this end, the coating 220 preferably further includes an isolator to isolate the protein and the non-photosensitive crosslinking agent, thereby preventing the protein from crosslinking with the non-photosensitive crosslinking agent in vitro.

[0060] In one alternative implementation, the protein, the separator, and the crosslinking agent together form a coating solution, but the separator is wrapped around the outer surface of the protein. In this implementation, the separator is generally a microsphere or microcapsule structure, capable of effectively encapsulating the protein. The microspheres and microcapsules can be prepared using existing technologies; for example, microspheres can be prepared using an emulsion solvent evaporation method, and microcapsules can be prepared using an in-situ polymerization method. Alternatively, in another alternative implementation, the coating 220 is a multilayer structure, for example, three layers: a first layer, a second layer, and a third layer. The first layer includes the protein but not the non-photosensitive crosslinking agent; the second layer includes the separator; and the third layer includes the non-photosensitive crosslinking agent but not the protein. The second layer is located between the first and third layers. In this implementation, it is only necessary to prepare solutions for each layer separately and form each layer sequentially, making the implementation simpler. It should be noted that, after entering the bloodstream, the separator should be able to decompose, dissolve, or degrade under the influence of body fluids, thereby allowing the protein to come into contact with the non-photosensitive cross-linking agent and undergo a cross-linking reaction. Optionally, the separator may include, but is not limited to, sustained-release materials, such as phospholipids, starch, polylactic acid, chitosan, etc.

[0061] It should also be noted that, in some embodiments, the crosslinking agent includes both the photosensitive crosslinking agent and the non-photosensitive crosslinking agent.

[0062] It is understood that the crosslinking agents are classified into physical crosslinking agents and chemical crosslinking agents. The physical crosslinking agents include at least one of tannic acid, pentagalloglucoside, gallic acid ester, gallic acid, ellagic acid, proanthocyanidins, anthocyanins, quercetin, luteolin, catechin, and epicatechin. The chemical crosslinking agent includes at least one of glutaraldehyde, polyepoxide, genipin, methylene blue, methylene green, rose red, riboflavin, proflavin, fluorescein, eosin, horseradish catalase, 4-amino-1,8-naphthylimide, 2,2'-((ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(6-((2-(2-(2-aminoethoxy)ethoxy)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione) and its salts, ammonium persulfate, ruthenium chloride terpyridine, camphorquinone, and curcumin.

[0063] Typically, the physical crosslinking agent is the non-photosensitive crosslinking agent. A portion of the chemical crosslinking agent is the non-photosensitive crosslinking agent, and the other portion is the photosensitive crosslinking agent. Specifically, the chemical crosslinking agents include methylene blue, methylene green, rose red, riboflavin, proflavin, fluorescein, eosin, 4-amino-1,8-naphthalimide, and 2,2'-((ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(6-((2-(2-(2-aminoethoxy)ethoxy)ethyl)amino)-1H-benzo[de]isoquinoline-1,3(2H)-dione) which are the photosensitive crosslinking agents.

[0064] Those skilled in the art will know that riboflavin, or vitamin B2, has the effect of reducing inflammatory responses and improving blood supply to the spindle. Therefore, in the embodiments of the present invention, the cross-linking agent preferably includes riboflavin.

[0065] In the coating solution, the mass ratio of the protein to the crosslinking agent is set as needed, typically 100:1 to 1:1, such as 100:1, 90:1, 80:1, 70:1, 65:1, 55:1, 40:1, 30:1, 20:1, 10:1, 5:1, 2:1, 1:1, etc.

[0066] In a further improved embodiment, the coating 220 also includes a drug. The type of drug is selected according to actual needs, such as antiproliferative drugs, anti-inflammatory drugs, anti-inflammatory agents, anti-proliferative drugs, antibacterial drugs, antitumor drugs, antimitotic drugs, cell-inhibiting drugs, cytotoxic drugs, anti-osteoporosis drugs, anti-angiogenic drugs, anti-restenosis drugs, microtubule-inhibiting drugs, anti-metastasis drugs, anti-thrombotic drugs, etc. Specific drugs include, but are not limited to, dexamethasone, prednisolone, corticosteroids, budesonide, estrogens, sulfasalazine and ammosalicylic acid, acemetidine, aescin, aminopterin, antifungals, arsenic trioxide, aristolochic acid, aspirin, berberine, ginkgo biloba extract, endothelial statins, angiotensin II, angiopeptides, monoclonal antibodies that can block the proliferation of smooth muscle cells, levofloxacin, paclitaxel, docetaxel, hydroxycamptothecin, vincristine, doxorubicin, and 5-fluorouracil. Cisplatin, thymidine kinase inhibitor antibiotics (especially actinomycin-D), hormones, antibody anticancer drugs, bisphosphonates, selective estrogen receptor modulators, strontium ranitidine, cyclosporine A, cyclosporine C, brefidobacterium A, vascular endothelial growth factor, angiogenesis factor, recombinant proteins, stem cells, rapamycin and its derivatives, including but not limited to zotamolimus, everolimus, biomus, 7-O-demethylrapamycin, tesimolimus, and desfolimox.

[0067] Since the medical balloon catheter can be used to treat atherosclerosis, the coating 220 may further include drugs that prevent or improve coronary microcirculation disorders. Such drugs include, but are not limited to, at least one of statins (such as ACEI / ARB), ranolazine, metoprolol, adenosine, nitrates, sodium nitroprusside, verapamil, nicorandil, and alprostadil.

[0068] As previously mentioned, the crosslinking agent in the coating 220 may include a photosensitive crosslinking agent, which needs to be activated under light. In this case, such as Figure 1 and Figure 6 , Figure 7 As shown, the medical balloon catheter also includes an optical fiber assembly 300, the distal end of which has a light-emitting portion 310. The optical fiber assembly 300 is at least partially inserted within the catheter body 100, and the light-emitting portion 310 extends to the distal end of the catheter body 100, with its position corresponding to the position of the balloon body 210. The distal end of the catheter body 100 is configured to allow light emitted from the light-emitting portion 310 to illuminate the balloon body 210, thereby activating the photosensitive crosslinking agent under light irradiation and generating free radicals, initiating a protein crosslinking reaction. Depending on the actual requirements, the axial length of the light-emitting portion 310 is selected between 1 mm and 50 mm.

[0069] In this embodiment of the invention, the optical fiber assembly 300 is preferably a columnar diffused optical fiber, which can provide lateral divergent light. In a specific embodiment, the optical fiber assembly 300 includes an optical fiber core 311, the distal end of which extends to the distal end of the conduit body 100 and corresponds to the position of the balloon body 210. The optical fiber assembly 300 also includes a scattering layer 312, which is located at least at the light-emitting part 310 and uniformly attached to the outer peripheral surface of the optical fiber core 311. The scattering layer 312 includes a matrix material and scattering particles uniformly dispersed in the matrix material. The scattering particles can scatter the light emitted by the optical fiber core 311 to provide circumferentially uniform divergent light.

[0070] In this embodiment of the invention, the diameter of the optical fiber core 311 is 0.05mm-1mm. The thickness of the scattering layer 312 is 0.1mm-0.5mm, the matrix material includes, but is not limited to, rubber, and the scattering particles include, but are not limited to, nano-titanium dioxide. It should be noted that when the scattering layer 312 is located only at the light-emitting part 310, the optical fiber assembly 300 further includes a protective layer 320, which is attached to the outer peripheral surface of the optical fiber core 311 and located near the scattering layer 312.

[0071] Further, please refer to Figure 6 The catheter body 100 includes an inner tube 110 and an outer tube 120. The inner tube 110 partially passes through the outer tube 120, and the distal end of the inner tube 110 extends from the distal end of the outer tube 120. The space between the inner surface of the outer tube 120 and the inner surface of the inner tube 110 forms the filling agent channel. The distal end of the outer tube 120 is sealed to a junction 212 at the proximal end of the balloon body 210, so that the filling agent channel communicates with the filling cavity of the balloon body 210. The inner tube 110 has an optical fiber channel (not shown in the figure), and the optical fiber assembly 300 is at least partially passed through the optical fiber channel of the inner tube 110. The distal end of the inner tube 110 is configured to allow light to pass through. Optionally, the inner tube 110 is entirely made of transparent polyethylene material, so that the light transmittance of the inner tube 110 is greater than 90%, to allow light emitted by the light-emitting part 310 to pass through.

[0072] Furthermore, similar to existing technologies, the inner tube 110 is also provided with a guidewire cavity 111, which extends axially through the inner tube 110 and runs parallel to the optical fiber channel. A guidewire inlet 101 is also formed on the proximal sidewall of the catheter body 100, communicating with the guidewire cavity 111 for inserting a guidewire. Additionally, the medical balloon catheter also includes a connector 400 connected to the proximal end of the catheter body 100, and includes a first interface 410 and a second interface 420. The first interface 410 communicates with the filling agent channel and is used for connection to a filling device, such as a syringe. The second interface 420 communicates with the inner tube 110 and allows the proximal end of the optical fiber assembly 300 to exit. Furthermore, the medical balloon catheter also includes a guide head 500 and a contrast-enhancing element 600. The guide head 500 is connected to the distal end of the inner tube 110 and located on the distal side of the medical balloon 200, and is also connected to the distal end of the fiber optic assembly 300. The guide head 500 is typically a tapered structure with an inner diameter that gradually decreases from proximal to distal, to facilitate guidance as the medical balloon catheter travels within the blood vessel at its distal end. The contrast-enhancing element 600 is disposed on the inner tube 110 and corresponds to the position of the medical balloon 200 for X-ray imaging and positioning of the medical balloon 200.

[0073] Furthermore, this embodiment of the invention also provides a preparation method for preparing the medical device as described above. The preparation method includes the following steps:

[0074] First, a substrate is provided, which is capable of expanding or contracting radially therein; the substrate is, for example, the sac-like body 210. Then, a coating solution is provided, comprising a protein and a crosslinking agent.

[0075] Next, the coating solution is sprayed onto at least a portion of the outer surface of the balloon body 210.

[0076] Finally, the coating solution is dried to form the coating 220.

[0077] Next, this article will introduce the preparation method of the medical balloon described in Example 1, and illustrate the therapeutic effect of the medical balloon catheter provided by the embodiments of the present invention by comparing Example 1 and the comparative example.

[0078] The cross-linking agent used in Example 1 is riboflavin, and the protein used is silk fibroin, with a mass ratio of silk fibroin to riboflavin of 10:1.

[0079] First, a coating solution is provided. The specific process involves adding riboflavin and silk fibroin to a solvent and dissolving them by ultrasound. In this embodiment, the solvent is a mixture of ethyl acetate and acetone, with a mass ratio of ethyl acetate to acetone of 3:1.

[0080] Next, the coating solution is applied to the outer surface of the main body 211 of the balloon body 210 by ultrasonic spraying, and the coating solution completely covers the outer surface of the main body 211.

[0081] Next, the coating solution is dried and cured at room temperature for 24 hours to form the coating 220.

[0082] In this embodiment, a total of six medical balloons 200 were prepared, which were labeled as medical balloon No. 1, medical balloon No. 2, medical balloon No. 3, medical balloon No. 4, medical balloon No. 5 and medical balloon No. 6 respectively. The specifications of each medical balloon are shown in Table 1 below.

[0083] The silk fibroin and riboflavin in the coating 220 of six medical balloons 200 were quantified, and the results are shown in Table 1. The calculated density of silk fibroin loaded in the coating 220 is approximately 0.13 mg / mm³. 2 The density of the supported crosslinking agent is approximately 0.012 mg / mm³. 2 .

[0084] The medical balloon 200, the catheter body 100, and the optical fiber assembly 300 are assembled to obtain the medical balloon catheter. The performance of the medical balloon catheter is then tested.

[0085] First, the target blood vessel is provided. The target blood vessel is the right iliac artery of a pig, whose surface tissue has been removed. The right iliac artery of a pig is 1 cm long, the thickness of the vessel wall is 2 mm, and the inner diameter of the vessel is 5 mm.

[0086] Take the medical balloon catheter prepared from the medical balloon 200 described in No. 1, wherein the medical balloon 200 is gripped.

[0087] The medical balloon 200 is inserted into the target blood vessel, and a filling agent is infused into the filling cavity of the balloon body 210 through the first interface 410 to inflate the balloon body 210, thereby bringing the coating 220 into contact with the vessel wall of the target blood vessel. In this step, the over-expansion ratio of the balloon body 210 is 125%. The over-expansion ratio refers to the ratio of the diameter of the balloon body 210 after expansion to the initial inner diameter of the target blood vessel (i.e., the inner diameter of the target blood vessel before treatment by the medical balloon 200).

[0088] Then, the light-emitting part 310 of the optical fiber assembly 300 emits a laser and irradiates the coating 220. The laser has a wavelength of 450nm, a power of 1W, and an irradiation time of 60s.

[0089] Subsequently, the filling agent is drained, and the medical balloon 200 is withdrawn from the target blood vessel.

[0090] Next, the wall thickness and inner diameter of the target blood vessel were measured, as shown in Table 2, and photographs were taken of the target blood vessel, as shown in the following figures. Figure 8 As shown in c.

[0091] Finally, the target blood vessel was immersed in formalin for a certain period of time and subjected to histochemical staining, followed by photographing, as shown in the image. Figure 9 As shown in c.

[0092] Comparative Example 1

[0093] The difference between this comparative example and Example 1 is that the coating 220 includes silk fibroin but not riboflavin. The operating procedures for treating the target vessel using the medical balloon catheter provided in this comparative example are exactly the same, and the over-expansion ratio of the medical balloon is also 125%. The parameters of the target vessel before and after treatment are shown in Table 2. Images of the target vessel after treatment with the medical balloon catheter provided in this comparative example and before histochemical staining are shown below. Figure 8 As shown in Figure a, the photograph after histochemical staining is as follows. Figure 9 As shown in Figure a.

[0094] Comparative Example 2

[0095] The difference between this comparative example and Example 1 is that the fiber optic assembly 300 was not used to irradiate the coating 220 when processing the target blood vessel. The preparation method of the medical balloon catheter provided in this comparative example is exactly the same as that provided in Example 1, and the over-expansion ratio of the medical balloon is also 125%. The parameters of the target blood vessel before and after processing are shown in Table 2. Images of the target blood vessel after processing with the medical balloon catheter provided in this comparative example and before histochemical staining are shown below. Figure 8 As shown in b, the photograph after histochemical staining is as follows. Figure 9 As shown in b.

[0096] Comparative Example 3

[0097] The difference between this comparative example and Example 1 is that the coating 220 includes riboflavin but not silk fibroin. The operating procedures for processing the target vessel using the medical balloon catheter provided in this comparative example are exactly the same, and the over-expansion ratio of the medical balloon is also 125%. The parameters of the target vessel after processing are shown in Table 2. Images of the target vessel after processing with the medical balloon catheter provided in this comparative example and before histochemical staining are shown below. Figure 8 As shown in d, the photograph after histochemical staining is as follows. Figure 9 As shown in d.

[0098] Table 1

[0099] Length / mm Inner diameter / mm Silk fibroin content / mg Riboflavin content / mg No. 1 13 3 15.1 1.4 No. 2 23 3 28.6 2.7 No. 3 28 3 33.9 3.2 No. 4 13 4 21.2 2.1 No. 5 23 4 37.3 3.6 No. 6 28 4 41.3 4.4

[0100] Table 2

[0101] Initial inner diameter of the target blood vessel / mm Initial thickness of the target blood vessel / mm The inner diameter of the target blood vessel after treatment (mm) Target blood vessel thickness after treatment (mm) Example 1 5 2 6 1.5 Comparative Example 1 6 1.5 6 1.5 Comparative Example 2 5 2 5 2 Comparative Example 3 5 2 5.5 1.5

[0102] Depend on Figure 8 and Figure 9 As can be seen, after the medical balloon catheter provided in Embodiment 1 of the present invention processes the target blood vessel, the cross-section of the target blood vessel shows a significant increase in protein color, and the protein fibers exhibit a tendency to be oriented along the circumferential direction of the blood vessel. In contrast, the target blood vessels processed by the medical balloon catheters provided in Comparative Examples 1 and 2 show a lighter protein color and less obvious fiber orientation in their cross-sections. The target blood vessel processed by the medical balloon catheter provided in Comparative Example 3 shows a certain degree of protein color deepening and some fiber orientation, but the color is lighter than in Embodiment 1, and the orientation is not as pronounced. This indicates that when the medical balloon catheter provided in the embodiments of the present invention processes the target blood vessel, the proteins on the coating 220 can be deposited and oriented on the blood vessel wall, forming a "protein microscaffold" in situ. Referring to Table 2, compared with Comparative Examples 1 and 2, it can be found that the inner diameter of the target blood vessel processed by the medical balloon catheter provided in Embodiment 1 of the present invention increases, and the vessel wall becomes thinner, indicating that the "protein microscaffold" can provide better support for the blood vessel wall, maintaining the blood vessel wall in an expanded state and reducing the possibility of restenosis. Compared with Comparative Example 3, it can be found that the medical balloon catheter provided in Example 1 has a more significant effect on increasing the inner diameter of the target blood vessel. This is because the additional introduction of protein through the coating increases the protein content, allowing the cross-linking reaction to occur fully, thereby effectively forming a "protein microscaffold" with sufficient support strength. This avoids the problem of insufficient support of the protein microscaffold leading to blood vessel wall retraction, i.e., the protein microscaffold cannot effectively support the blood vessel wall.

[0103] In summary, the proteins in the coating of the medical balloon of the medical balloon catheter provided in this embodiment of the invention, through the action of a cross-linking agent, can undergo a cross-linking reaction with the proteins of the blood vessel wall, forming a "protein microscaffold" in situ. The mechanical properties of the "protein microscaffold" are used to support the dilated blood vessel, keeping the blood vessel in an dilated state and reducing restenosis.

[0104] While the present invention has been disclosed above, it is not limited thereto. Those skilled in the art can make various modifications and variations to the present invention without departing from its spirit and scope. Therefore, if such modifications and variations fall within the scope of the claims and their equivalents, the present invention also intends to include such modifications and variations.

Claims

1. A medical device, characterized in that, The device includes a matrix and a coating, the matrix being capable of expanding or contracting radially therein; the coating is disposed on at least a portion of the outer surface of the matrix, and the coating includes a protein, an isolator, and a crosslinking agent; the protein includes at least one of humanized elastin, humanized collagen, human serum albumin, silk fibroin, and proteoglycan; the crosslinking agent includes a non-photosensitive crosslinking agent; the isolator includes phospholipid compounds, starch, polylactic acid, and chitosan; the isolator encapsulates the outer surface of the protein to prevent the protein from undergoing a crosslinking reaction with the non-photosensitive crosslinking agent.

2. The medical device according to claim 1, characterized in that, The non-photosensitive crosslinking agent includes physical crosslinking agents and / or chemical crosslinking agents, wherein the chemical crosslinking agent includes at least one of glutaraldehyde, polyepoxide, genipin, horseradish catalase, and ammonium persulfate.

3. The medical device according to claim 2, characterized in that, The physical crosslinking agent includes at least one of tannic acid, pentagalloglucoside, gallic acid ester, gallic acid, ellagic acid, proanthocyanidins, anthocyanins, quercetin, luteolin, catechin, and epicatechin.

4. The medical device according to claim 1, characterized in that, The mass ratio of the protein to the cross-linking agent is 100:1 to 1:

1.

5. The medical device according to claim 1, characterized in that, The substrate includes a main body; the coating is disposed on at least a portion of the outer surface of the main body.

6. The medical device according to claim 5, characterized in that, The coating covers the entire outer surface of the main body.

7. The medical device according to claim 6, characterized in that, The coating comprises a plurality of sub-coatings, which are arranged at intervals along the axial direction of the main body.

8. The medical device according to claim 6, characterized in that, The coating has a spiral structure surrounding the axis of the main body.

9. The medical device according to claim 6, characterized in that, The coating has a mesh-like structure.

10. The medical device according to claim 1, characterized in that, The coating also includes a drug.

11. The medical device according to claim 1, characterized in that, The matrix includes a balloon or a stent.

12. A medical system, characterized in that, The medical device and catheter body included in any one of claims 1-11, wherein the base is fitted onto the distal outer peripheral surface of the catheter body.

13. The medical system according to claim 12, characterized in that, The crosslinking agent includes a photosensitive crosslinking agent; the medical system further includes an optical fiber assembly, which is at least partially inserted into the catheter body, the optical fiber assembly including a light-emitting portion extending to the distal end of the catheter body, and the position of the light-emitting portion corresponding to the position of the substrate; the distal end of the catheter body is configured to allow light emitted by the light-emitting portion to irradiate the substrate.

14. The medical system according to claim 13, characterized in that, The light transmittance of the distal end of the catheter is greater than 90%.

15. A method for preparing a medical device as described in any one of claims 1-11, characterized in that, The preparation method includes the following steps: The matrix and coating solution are provided, the matrix being capable of expanding or contracting radially therein, and the coating solution comprising the protein, the separator, and the crosslinking agent; The coating solution is applied to at least a portion of the outer surface of the substrate; The coating solution is dried to form the coating.

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