Novel vascular interventional medical device

Abstract

The present application discloses a novel vascular interventional medical device, comprising: a tube body, provided with a distal end and a proximal end opposite to each other, wherein the tube body provides at least a fluid channel and an optical fiber channel; a balloon body, located on the periphery of a distal end portion of the tube body and communicating with the fluid channel; an optical fiber, penetrating through the optical fiber channel and provided with a light-emitting section extending to the position where the balloon body is located; and a light source, connected to the optical fiber by means of an optical path and configured for exciting the optical fiber to emit light with a predetermined wavelength. The periphery of the balloon body is provided with a fat-soluble photosensitizer coating, and the fat-soluble photosensitizer is at least one of a riboflavin ester, curcumin, chlorophyll a, and chlorin e6. The novel vascular interventional medical device provided in the present application can deliver the photosensitizer to a target lesion site more efficiently. Moreover, the photosensitizer can stay uniformly on the inner wall of a blood vessel for a long time and form a natural stent more efficiently while reducing damage to an unexpected site.

Description

A novel vascular interventional medical device Technical Field

[0001] This application relates to the field of medical device technology, and in particular to a novel vascular interventional medical device. Background Technology

[0002] Coronary artery disease is an increasingly common and serious cardiovascular disease characterized by progressive atherosclerotic stenosis. Recent advancements in natural vascular stent therapy offer an alternative to traditional stents. These stents form naturally occurring scaffolds by covalently cross-linking with collagen and elastin in the arterial wall, reducing inflammation associated with foreign stent implantation, maintaining luminal gain after angioplasty, and minimizing elastic recoil.

[0003] Natural vascular stent therapy uses a photosensitizer-infused balloon dilatation catheter. Unlike traditional drug-eluting balloons, the balloon portion of this type of catheter can scatter visible light, activating the photosensitizer and inducing rapid binding of collagen and elastin in the blood vessel wall, forming a stent in situ and achieving vascular healing and repair. Technical issues

[0004] However, commonly used photosensitizers are water-soluble, which can easily detach from the balloon when passing through blood vessels, resulting in a lower concentration of photosensitizer reaching the intended site and affecting the effectiveness of interventional treatment. At the same time, water-soluble photosensitizers can easily pass through blood vessels and penetrate the outer wall of the blood vessel, which can easily cause damage to unintended sites. Technical solutions

[0005] Based on this, a novel vascular interventional medical device is provided that can deliver photosensitizers more efficiently to the target lesion site. At the same time, the photosensitizers can remain evenly and for a long time on the inner wall of the blood vessel, forming a natural stent more efficiently, while reducing damage to unintended sites.

[0006] A novel vascular interventional medical device includes:

[0007] A tube body having a distal end and a proximal end, the tube body providing at least a fluid channel and an optical fiber channel;

[0008] The balloon body is located on the outer periphery of the distal end of the tube and is in communication with the fluid channel;

[0009] An optical fiber is inserted through the optical fiber channel and has a light-emitting segment extending to the location of the balloon body;

[0010] A light source, connected to the optical fiber path, is used to excite the optical fiber to emit light of a predetermined wavelength.

[0011] The outer periphery of the balloon is coated with a lipid-soluble photosensitizer, which is at least one of riboflavin, riboflavin derivatives, curcumin, curcumin derivatives, chlorophyll a, and dihydroporphyrin e6.

[0012] 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.

[0013] Optionally, the riboflavin derivative is one of riboflavin tetrapalmitate, riboflavin tetradecanoate, riboflavin tetrabutyrate, riboflavin tetraacetate, riboflavin tryptophan tetraester, riboflavin laurate, riboflavin isobutyrate, riboflavin-2,6-dimethoxybenzoate, and riboflavin adamantinate; the curcumin derivative is one of hydroxyacetylated curcumin, curcumin salicyl monoester, and demethoxycurcumin.

[0014] Optionally, the amount of lipid-soluble photosensitizer in the lipid-soluble photosensitizer coating is 0.05~10 μg / mm. 2 .

[0015] Optionally, the thickness of the lipid-soluble photosensitizer coating is 0.1~10 μm. More preferably, the thickness of the lipid-soluble photosensitizer coating is 0.3~3 μm.

[0016] Optionally, the outer periphery of the balloon is further provided with a drug coating, wherein the drug is at least one of rapamycin, sirolimus, everolimus, zotamolimus, 42-(dimethylphosphono)rapamycin, desfolimus, biolimus, umimilimus, tacrolimus, paclitaxel, and sorafenib.

[0017] Optionally, the amount of drug in the drug coating is 0.1~10 μg / mm. 2 .

[0018] Optionally, the thickness of the drug coating is 0.1~10μm.

[0019] Optionally, the ratio of the lipid-soluble photosensitizer to the drug is 20:1 to 1:50.

[0020] Optionally, the lipid-soluble photosensitizer is dissolved in a solvent, and the resulting solution is coated on the surface of the capsule and dried to obtain the lipid-soluble photosensitizer coating. The concentration of the lipid-soluble photosensitizer in the solution is 0.5~150 mg / mL.

[0021] Optionally, the lipid-soluble photosensitizer coating is located between the drug coating and the outer surface of the balloon. Beneficial effects

[0022] The novel vascular interventional medical device provided in this application can deliver photosensitizers to the target lesion site more efficiently, while the photosensitizers can remain uniformly and for a long time on the inner wall of the blood vessel, forming a natural stent more efficiently, and reducing damage to unintended sites. Attached Figure Description

[0023] Figure 1 is a schematic diagram of the structure of a novel vascular interventional medical device;

[0024] Figure 2 is a schematic diagram of the surface coating of the balloon body in a novel vascular interventional medical device. Embodiments of the present invention

[0025] 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.

[0026] To better describe and illustrate the embodiments of this application, reference may be made to one or more accompanying drawings, but the additional details or examples used to describe the drawings should not be considered as limiting the scope of any of the inventive creations of this application, the embodiments or preferred methods described herein.

[0027] 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.

[0028] 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 be limiting of the application.

[0029] Referring to Figure 1, a novel vascular interventional medical device 100 includes:

[0030] The tube body 200 has a relatively distal end and a proximal end, and the tube body provides at least a fluid channel and an optical fiber channel;

[0031] The balloon body 300 is located on the outer periphery of the distal part of the tube body 200 and is in communication with the fluid channel;

[0032] Fiber 400 is inserted into the fiber optic channel and has a light-emitting segment that extends to the location of the balloon body 300.

[0033] The light source 500 is connected to the optical fiber 400 optical path to excite the optical fiber to emit light of a predetermined wavelength.

[0034] The periphery of the sac 300 has a coating of a lipid-soluble photosensitizer, which is at least one of riboflavin, riboflavin derivatives, curcumin, curcumin derivatives, chlorophyll a, and dihydroporphyrin e6.

[0035] The tube body 200 can be a multi-cavity tube, with different cavities serving as fluid channels and fiber optic channels respectively. Alternatively, multiple tubes extending side by side can be used, with the inner cavities of different tubes serving as fluid channels and fiber optic channels respectively, as shown in Figure 1. The tube body includes inner and outer tubes nested together. The radial gap between the inner and outer tubes serves as a fluid channel and also as a fiber optic channel.

[0036] Referring to Figure 1, a pipe connector 600 is connected to the near end of the pipe body 200. The pipe connector is provided with a first channel 620 that communicates with the fluid channel and a second channel 610 that communicates with the optical fiber channel.

[0037] The proximal end of the balloon body 300 is sealed to the distal end of the outer tube of the tubing, and the distal end of the balloon body is sealed to the distal end of the inner tube of the tubing. Fluid enters and fills the balloon body 300 through the radial gap between the outer and inner tubes. One end of the optical fiber 400 is connected to the light source 500, and the other end extends into the balloon body 300 as a light-emitting segment, the length of which is equal to the axial length of the balloon body. The optical fiber 400 travels along the inner tube of the tubing and is fixedly connected to the inner tube wall.

[0038] Riboflavin, also known as vitamin B2, reacts with acid to form riboflavin esters. Preferably, the riboflavin derivative is one of riboflavin tetrapalmitate, riboflavin tetradecanoate, riboflavin tetrabutyrate, riboflavin tetraacetate, riboflavin tryptophan tetraester, riboflavin laurate, riboflavin isobutyrate, riboflavin-2,6-dimethoxybenzoate, and riboflavin adamantinate. The curcumin derivative is one of hydroxyacetylated curcumin, curcumin salicylyl monoester, and demethoxycurcumin.

[0039] Riboflavin tetrabutyl ester, also known as riboflavin tetrabutyrate, CAS number: 752-56-7, has the following structural formula:

[0040] .

[0041] Riboflavin tetraethyl ester, also known as riboflavin tetraacetate, CAS number: 752-13-6, has the following structural formula:

[0042] .

[0043] This application uses riboflavin tetrabutyl ester or riboflavin tetraethyl ester as a lipid-soluble photosensitizer to form a coating on the outer surface of the balloon body. The lipid-soluble photosensitizer is delivered to the target lesion site of the blood vessel through the balloon body. It forms a natural scaffold by covalently cross-linking with collagen and elastin in the arterial wall. The lipid-soluble photosensitizer is not easy to fall off before crossing the blood vessel to reach the target lesion site, and the delivery efficiency is higher.

[0044] When using water-soluble photosensitizers, they are prone to detaching from the balloon and being lost into the bloodstream during the process of crossing blood vessels, thus failing to effectively reach the target lesion site. Therefore, it is necessary to characterize the loss of photosensitizers in the blood.

[0045] The characterization method was as follows: First, following standard clinical procedures, the guiding catheter and guidewire, which matched the balloon, were sequentially inserted into the vascular model (containing water as simulated blood). Second, the balloon catheter was removed from the packaging, the guidewire was inserted into the balloon catheter, and it was pushed to the simulated lesion location. Finally, the balloon was removed and immersed in water or a solvent (if it was a water-soluble photosensitizer, it was immersed in water; if it was a lipid-soluble photosensitizer, it was immersed in the corresponding solvent). The remaining photosensitizer content on the balloon was measured using HPLC. The test results are shown in Table 1.

[0046] Table 1

[0047] Photosensitizer Number | Properties | Average Loss Rate 1. Riboflavin Tetrabutyl Ester | Lipid-soluble | 8% 2. Riboflavin Laurate | Lipid-soluble | 13% 3. Riboflavin Isobutyrate | Lipid-soluble | 15% 4. Riboflavin Tetraethyl Ester | Lipid-soluble | 13% 5. Curcumin | Lipid-soluble | 15% 6. Hydroxyacetylated Curcumin | Lipid-soluble | 20% 7. Demethoxylated Curcumin | Lipid-soluble | 16% 8. Chlorophyll a | Lipid-soluble | 20% 9. Dihydroporphyrin e6 | Lipid-soluble | 18% 10. Riboflavin Sodium Phosphate | Water-soluble | 53% 11. Naphthalimide Diacetate | Salt-soluble | 45% 12. Bengal Rose Red | Water-soluble | 74%

[0048] As shown in Table 1, the loss rate of water-soluble photosensitizers after passing through simulated blood is over 45%, while the loss rate of lipid-soluble photosensitizers is less than 20%, meaning that more than 80% of lipid-soluble photosensitizers can reach the target site and exert their photosensitizing effect. Even better, the loss rates of riboflavin tetrabutyl ester and riboflavin tetraethyl ester are less than 13%.

[0049] Water-soluble photosensitizers not only have a high loss rate during delivery, but even when they reach the target lesion site, they have a limited residence time on the inner wall of the blood vessel and are more likely to diffuse to the outer wall of the blood vessel. The outer wall of the blood vessel is not the intended location for stent formation. At the same time, the photosensitizer itself generates reactive oxygen species under light, which can damage the outer wall of the blood vessel.

[0050] This application uses a lipid-soluble photosensitizer that can reach the target lesion site in the blood vessel more efficiently, while being evenly distributed on the inner wall of the blood vessel. It can remain in the inner wall of the blood vessel for a longer time and will not diffuse to the outer wall of the blood vessel, causing unintended damage.

[0051] In this application, riboflavin ester is used as a photosensitizer. It is a reducing agent. When light causes the photosensitizer to generate reactive oxygen species, the reactive oxygen species will destroy collagen and lead to calcification. As a reducing agent, riboflavin ester can undergo an oxidation-reduction reaction with the reactive oxygen species, thereby reducing the damage to the blood vessel wall.

[0052] Due to the oxidative effect of lipid-soluble photosensitizers, their dosage needs to be appropriate, limited to achieving covalent cross-linking of collagen and elastin to form a natural scaffold. The dosage of lipid-soluble photosensitizer in the coating is 0.05~10 μg / mm. 2 The thickness of the lipid-soluble photosensitizer coating is 0.1~10μm. More preferably, the thickness of the lipid-soluble photosensitizer coating is 0.3~3μm.

[0053] To promote vascular repair, the balloon is also coated with a drug, which is at least one of the following: rapamycin, sirolimus, everolimus, zotamolimus, 42-(dimethylphosphono)rapamycin, desfolimus, biolimus, umimilimus, tacrolimus, paclitaxel, protazoline, and sorafenib.

[0054] The dosage of the drug in the drug coating is 0.1~10 μg / mm. 2 The thickness of the drug coating is 0.1~10μm.

[0055] In this application, a lipid-soluble photosensitizer is used, which can share the same solvent as the drug. The solvent can be methanol, ethanol, formic acid, acetic acid, acetonitrile, isopropanol, acetone, ethyl acetate, n-hexane, cyclohexane, dichloromethane, methyl acetate, butyl acetate, carbon tetrachloride, butanone, n-hexane, n-pentane, n-heptane, etc. As a reducing agent, the lipid-soluble photosensitizer can protect the drug; it is also a drug itself and can exert an antithrombotic effect.

[0056] The ratio of the lipid-soluble photosensitizer to the drug is 20:1 to 1:50. More preferably, the ratio of the lipid-soluble photosensitizer to the drug is 1:1 to 1:10.

[0057] In preparing the lipid-soluble photosensitizer coating, the lipid-soluble photosensitizer is dissolved in a solvent, and the resulting solution is coated on the surface of the capsule and dried to obtain the lipid-soluble photosensitizer coating. The concentration of the lipid-soluble photosensitizer in the solution is 0.5~150 mg / mL.

[0058] In solution, a high concentration of lipid-soluble photosensitizer is required for effective coating. The riboflavin ester used in this application has sufficient solubility in the solvent, allowing for repeated coating and drying processes to obtain the final coating. Similarly, drug coatings can also be prepared using a multiple-coating and drying process.

[0059] Drug coating and lipid-soluble photosensitizer coating can also be prepared simultaneously by dissolving the drug and lipid-soluble photosensitizer in the same solvent and then forming a coating on the capsule. In this way, the drug coating and lipid-soluble photosensitizer coating are combined into one, and there is no longer a clear boundary between the two coatings. The lipid-soluble photosensitizer is not easy to fall off, which can protect the drug coating from falling off.

[0060] Alternatively, the drug coating and the lipid-soluble photosensitizer coating can be prepared separately, as shown in Figure 2. The lipid-soluble photosensitizer coating 700 is located between the drug coating 800 and the outer surface of the balloon. The lipid-soluble photosensitizer coating 700 is encapsulated within the drug coating 800, allowing the lipid-soluble photosensitizer to reach the target lesion site more efficiently.

[0061] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0062] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively 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 patent application should be determined by the appended claims.

Claims

1. A novel vascular interventional medical device, characterized in that, include: A tube body having a distal end and a proximal end, the tube body providing at least a fluid channel and an optical fiber channel; The balloon body is located on the outer periphery of the distal end of the tube and is in communication with the fluid channel; An optical fiber is inserted through the optical fiber channel and has a light-emitting segment extending to the location of the balloon body; A light source, connected to the optical fiber path, is used to excite the optical fiber to emit light of a predetermined wavelength. The feature is that the outer periphery of the balloon has a lipid-soluble photosensitizer coating, wherein the lipid-soluble photosensitizer is at least one selected from riboflavin, riboflavin derivatives, curcumin, curcumin derivatives, chlorophyll a, and dihydroporphyrin e6.

2. The novel vascular interventional medical device according to claim 1, characterized in that, The riboflavin derivative is one of riboflavin tetrapalmitate, riboflavin tetradecanoate, riboflavin tetrabutyrate, riboflavin tetraacetate, riboflavin tryptophan tetraester, riboflavin laurate, riboflavin isobutyrate, riboflavin-2,6-dimethoxybenzoate, and riboflavin adamantinate; the curcumin derivative is one of hydroxyacetylated curcumin, curcumin salicyl monoester, and demethoxycurcumin.

3. The novel vascular interventional medical device according to claim 1, characterized in that, The amount of lipid-soluble photosensitizer used in the coating is 0.05~10 μg / mm. 2 .

4. The novel vascular interventional medical device according to claim 1, characterized in that, The thickness of the lipid-soluble photosensitizer coating is 0.1~10μm.

5. The novel vascular interventional medical device according to any one of claims 1 to 4, characterized in that, The outer periphery of the balloon is further coated with a drug, which is at least one of rapamycin, sirolimus, everolimus, zotamolimus, 42-(dimethylphosphono)rapamycin, desfolimus, biolimus, umimilimus, tacrolimus, paclitaxel, and sorafenib.

6. The novel vascular interventional medical device according to claim 5, characterized in that, The amount of drug used in the drug coating is 0.1~10 μg / mm. 2 .

7. The novel vascular interventional medical device according to claim 5, characterized in that, The thickness of the drug coating is 0.1~10μm.

8. The novel vascular interventional medical device according to claim 5, characterized in that, The ratio of the lipid-soluble photosensitizer to the drug is 20:1 to 1:

50.

9. The novel vascular interventional medical device according to any one of claims 1 to 4, characterized in that, A lipid-soluble photosensitizer is dissolved in a solvent, and the resulting solution is coated onto the surface of a balloon and dried to obtain the lipid-soluble photosensitizer coating. The concentration of the lipid-soluble photosensitizer in the solution is 0.5~150 mg / mL.

10. The novel vascular interventional medical device according to claim 5, characterized in that, The lipid-soluble photosensitizer coating is located between the drug coating and the outer surface of the balloon.

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