A method of making a surface coating for an occluder and products thereof

By preparing a coating of cationic polymer, anionic monomer and siloxane crosslinking agent on the surface of the occluder, the problems of thrombosis and delayed endothelialization after occluder implantation are solved, achieving anticoagulant function and rapid endothelialization. The coating has high stability and can meet the folding and deployment requirements of the occluder.

CN116672514BActive Publication Date: 2026-02-03ZHEJIANG UNIV
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Patent Information

Application Number
CN202310598390.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-05-25
Publication Date
2026-02-03
Estimated Expiration
2043-05-25

AI Technical Summary

Technical Problem

Existing occluders are prone to thrombosis after implantation in the heart, have slow endothelialization, and the coating is easily detached during delivery, making it difficult to deploy them in one go.

Method used

A coating was prepared on the surface of the occluder by using a combination of cationic polymers, anionic monomers, siloxane crosslinking agents and photoinitiators, and by UV curing and heat curing. The coating has anticoagulant function, promotes endothelial cell adhesion and migration, and improves stability.

Benefits of technology

The prepared coating can prevent platelet adhesion and activation, reduce coagulation risk, promote endothelialization process, and has excellent stability, making it suitable for the actual use environment of the occluder.

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Abstract

The application discloses a preparation method of a surface coating of a plugging device, which comprises the following steps: (1) blending a cationic polymer, an anionic monomer, a siloxane crosslinking agent, a photoinitiator and a solvent to obtain a prepolymer solution; the cationic polymer is selected from polyethyleneimine and / or gelatin; the anionic monomer is selected from 2-acrylamido-2-methylpropanesulfonic acid; when the cationic polymer is selected from polyethyleneimine, a bioactive polypeptide needs to be added; (2) coating the prepolymer solution on a pretreated surface of the plugging device, initiating polymerization under ultraviolet light, and then performing heat curing. The application discloses a preparation method of a surface coating of a plugging device, the preparation process is simple and controllable, the plugging device treated by the method has excellent anticoagulation function, endothelialization is rapid, and the stability of the surface coating is excellent.
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Description

Technical Field

[0001] This invention relates to the technical field of medical devices, and in particular to a method for preparing a surface coating for an occluder and the product thereof. Background Technology

[0002] Transcatheter occlusion (TCA) has become an important method for minimally invasive treatment of congenital heart diseases such as atrial septal defect (VSD), ventricular septal defect (ASD), patent ductus arteriosus (PDA), and patent foramen ovale (PFO). The structures of occluders already used clinically mainly include a sealing disc, a choke membrane, and sutures. The choke membrane, typically made of polyester fiber, functions to seal the defect and prevent blood shunting. The sealing disc and occluder skeleton are made of nickel-titanium alloy wire. Existing occluders have the following problems:

[0003] 1. After the occluder is implanted in the heart, it comes into direct contact with the blood, making it prone to thrombus formation on its surface. Patients still need to take oral anticoagulants. If the thrombus dislodges and enters the bloodstream, it can cause a serious stroke. Therefore, the surface of the occluder needs to have good blood compatibility.

[0004] 2. After implantation of the occluder, endothelialization needs to be expedited to shorten the time required for patients to take oral anticoagulants. However, currently used occluders in clinical practice often result in delayed or incomplete endothelialization. Therefore, the occluder needs a surface that promotes endothelial cell adhesion, proliferation, and migration to accelerate endothelialization.

[0005] 3. During delivery within the sheath, the occluder is in a folded state, subjecting it to significant shear and frictional forces from the sheath's inner wall. Furthermore, deployment is difficult in a single step, requiring multiple retractions and detours. This necessitates a stable bonding capability for the occluder's surface coating. Existing non-covalently bonded biocompatible coatings are prone to detachment during delivery. Covalently bonded biocompatible coatings require complex chemical modifications to the occluder surface, and the combined modification of nickel-titanium alloy wire and polyester fiber is extremely challenging due to their differing chemical properties.

[0006] Therefore, designing a coating for the occluder surface to inhibit surface coagulation after occluder implantation and accelerate surface endothelialization is of great significance. At the same time, due to the special structure of the occluder, preparing a coating on its surface is very challenging. Summary of the Invention

[0007] To address the aforementioned problems in the existing technology, this invention discloses a method for preparing a surface coating for an occluder. The preparation process is simple and controllable, and the occluder treated by this method exhibits excellent anticoagulant function, rapid endothelialization, and excellent stability of the surface coating.

[0008] The specific technical solution is as follows:

[0009] A method for preparing a coating on the surface of a plugging device includes the following steps:

[0010] (1) A prepolymer solution is obtained by blending cationic polymer, anionic monomer, siloxane crosslinking agent, photoinitiator and solvent;

[0011] The cationic polymer is selected from polyethyleneimine and / or gelatin;

[0012] The anionic monomer is selected from 2-acrylamido-2-methylpropanesulfonic acid;

[0013] When the cationic polymer is selected from polyethyleneimine, bioactive peptides also need to be added;

[0014] (2) The prepolymer solution is coated on the surface of the pretreated plug, polymerization is initiated by ultraviolet light, and then cured by heating.

[0015] This preparation process involves selecting a specific combination of cationic polymers and anionic monomers, and adding a siloxane crosslinking agent. A coating is then formed on the occluder surface through simple UV curing and heat curing. The preparation process is simple, controllable, and easily scalable for industrial production. The resulting coating prevents platelet adhesion and activation, exhibiting anticoagulant properties, ensuring no coagulation reaction after implantation and reducing the risk of complications. Furthermore, the coating promotes endothelial cell adhesion and migration, accelerating endothelialization of the occluder surface after implantation. The coating also demonstrates excellent stability, exhibiting high retention and low swelling rate after 100 repeated folding cycles, making it more adaptable to the actual operating environment of the occluder.

[0016] Experiments have shown that if other common types of cationic polymers and anionic monomers are chosen to replace them, either the prepared coating will swell significantly or the prepared coating will dissolve, neither of which can be used effectively.

[0017] In step (1):

[0018] The weight-average molecular weight of the cationic polymer is 1,000 to 150,000 Da; preferably 10,000 to 100,000 Da.

[0019] Experiments have shown that the addition of the siloxane crosslinking agent in this invention not only significantly improves the stability of the prepared coating, but more importantly, it also inhibits the swelling of the coating.

[0020] The siloxane crosslinking agent is selected from conventional types in the art and has no special requirements. Specifically, it can be selected from at least one of 3-(trimethoxysilyl)methacrylate, O-(methacryloyloxyethyl)-N-(triethoxysilylpropyl)carbamate, vinyltriethoxysilane, and vinyltrimethoxysilane.

[0021] The photoinitiator is selected from conventional types in the field and there are no special requirements. Specifically, it can be selected from benzophenone, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone (I2959), etc.

[0022] The bioactive peptide is selected from one or more of the following: arginine-glycine-aspartic acid sequence peptide modified with acrylic acid (RGD), RGD modified with methacrylic acid, arginine-glutamine-aspartic acid-valine sequence peptide modified with acrylic acid (REDV), REDV modified with methacrylic acid, isoleucine-lysine-alanine-valine sequence peptide modified with acrylic acid (IKVAV), IKVAV modified with methacrylic acid, tyrosine-isoleucine-glycine-tryptophan-arginine modified with acrylic acid (YIGSR), and YIGSR modified with methacrylic acid.

[0023] The solvent is selected from a mixture of ethanol and water.

[0024] In step (1):

[0025] Based on the total mass of the prepolymer solution as 100%, the mass fraction of the cationic polymer is 0.1-10%, the mass fraction of 2-acrylamido-2-methylpropanesulfonic acid is 0.1-20%, the mass fraction of the siloxane crosslinking agent is 0.01-1%, and the mass fraction of the photoinitiator is 0.01-1%.

[0026] Preferably, based on the total mass of the prepolymer solution (100%), the mass fraction of the cationic polymer is 0.1-10%, and the mass fraction of 2-acrylamido-2-methylpropanesulfonic acid is 0.1-10%.

[0027] If it contains bioactive polypeptides, the mass fraction is 0.01% to 1% based on the total mass of the prepolymer solution (100%).

[0028] In the solvent, the mass ratio of ethanol to water is 0.25 to 4:1.

[0029] Experiments have shown that controlling the molar ratio of cationic polymer to anionic monomer is crucial in this preparation method. If the molar ratio is too small, significant swelling will occur, while if the molar ratio is too large, dissolution will result.

[0030] Preferably, the molar ratio of the cationic polymer to the anionic polymer monomer is 0.9 to 1.1:1; more preferably, it is 1.0 to 1.1:1.

[0031] Further preferred, the cationic polymer is selected from polyethyleneimine. Experiments have shown that coatings prepared by combining polyethyleneimine with 2-acrylamido-2-methylpropanesulfonic acid have better stability and faster endothelialization process.

[0032] In step (2):

[0033] The pretreated plug is an oxygen plasma activated plug;

[0034] The oxygen plasma activation involves an oxygen plasma generation frequency of 40 kHz to 13.56 MHz and an activation time of 1 to 60 min.

[0035] The coating includes one or more of spin coating, dip coating, and ultrasonic spraying;

[0036] The polymerization is initiated by ultraviolet light, with an ultraviolet light intensity of 10–200 mW / cm². 2 The UV polymerization time is 1–10 min;

[0037] The heating and curing process takes place at a temperature of 50–80°C.

[0038] The present invention also discloses a product prepared according to the above method, namely a two-component cross-linked coating applied to the surface of a plug.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] This invention discloses a method for preparing a coating on the surface of a plug, which uses widely available raw materials, has a simple and controllable preparation process, and is easy to industrialize.

[0041] This invention utilizes a combination of specially formulated cationic polymers and anionic monomers, along with the addition of siloxane crosslinking agents and selectively added bioactive peptides, to achieve a two-component crosslinked coating on the surface of an occluder through simple curing. This coating possesses anticoagulant properties, preventing coagulation reactions after implantation and reducing the risk of complications. Furthermore, the coating promotes endothelial cell adhesion and migration, accelerating endothelialization of the occluder surface after implantation. The coating also exhibits excellent stability, maintaining a high retention rate and low swelling rate after 100 repeated folding cycles, making it more adaptable to the actual operating environment of the occluder. Attached Figure Description

[0042] Figure 1 Scanning electron microscope images of the surface morphology of the coatings prepared in Example 1, Comparative Examples 1, 2 and 4 after immersion in physiological saline for 24 hours;

[0043] Figure 2 These are scanning electron microscope images of platelet adhesion on the surface of the occluder after treatment in Example 1, Comparative Example 1, and Comparative Example 7, respectively.

[0044] Figure 3 The table shows the number of endothelial cells on the surface of the occluder after treatment with Comparative Example 1, Example 1, and Example 4, respectively, at 4 h, 24 h, and 72 h after seeding.

[0045] Figure 4 These are laser confocal images showing the adhesion state of endothelial cells on the surface of the occluders treated in Example 1 and Comparative Example 1 after 72 hours on the seed plate.

[0046] Figure 5 This is a laser confocal image showing the adhesion state of endothelial cells on the surface of the occluder treated in Example 4 after 72 hours on the seed plate;

[0047] Figure 6 The above are bar charts showing the swelling degree data of the coatings prepared in Examples 1-3 and Comparative Examples 2-7, respectively.

[0048] Figure 7 Laser confocal images of the surface coatings of the occluders prepared in Examples 1, 4 and Comparative Example 2 before and after repeated 100 folds;

[0049] Figure 8 The bar chart shows the coating retention rate of the coatings prepared in Examples 1, 4 and Comparative Example 2 after 100 folds. Detailed Implementation

[0050] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0051] Example 1: Two-component plugging device coating of polyvinylimide / poly2-acryloylamino-2-methyl-1-propanesulfonic acid

[0052] Step 1: Pretreatment: The surface of the plug was treated with a 13.56MHz oxygen plasma cleaner. The plug was selected from Lifetech's Lambre™ plug, and the activation treatment time was 30 minutes.

[0053] Step 2: Preparation of prepolymer solution: Polyethyleneimine (weight average molecular weight of 70,000 Da), 2-acrylamido-2-methylpropanesulfonic acid, acrylic acid-modified RGD peptide (AAc-RGD), 3-(trimethoxysilyl)propyl methacrylate, photoinitiator I2959 and ethanol / water mixed solution (mass ratio of ethanol to water of 1:1) are mixed and shaken thoroughly to prepare the prepolymer solution;

[0054] The prepolymer solution contains 0.9% 2-acrylamido-2-methylpropanesulfonic acid and 0.5% polyethyleneimine, with a molar ratio of 1:1. The photoinitiator I2959 contains 0.5% 2-acrylamido-2-methylpropanesulfonic acid and 0.5% polyethyleneimine, respectively. The photoinitiator I2959 contains 0.5% 2-(trimethoxysilyl)methacrylate and 0.1% AAc-RGD.

[0055] Step 3: Ultrasonic spraying to prepare the coating: The prepolymer solution prepared in Step 2 is sprayed at a rate of 40 μL / min for 10 min to ensure that the prepolymer solution uniformly covers the surface of the plug; after spraying, the coating is polymerized in a UV chamber for 5 min at an UV lamp intensity of 100 mW / cm². 2 .

[0056] Step 4: Thermal cross-linking and curing of the coating: Place the plugging device treated in Step 3 in an oven at 60°C and heat for 2 hours to cure. Store the cured plugging device in a cool place.

[0057] Comparative Example 1

[0058] The occluder from Example 1 is used, but it is subjected to the same pretreatment process as in step 1 of Example 1.

[0059] Comparative Example 2

[0060] The preparation process is basically the same as in Example 1, except that no siloxane crosslinking agent was added to the prepolymer solution prepared in step 2, and the concentrations of other raw materials are exactly the same as in Example 1.

[0061] Comparative Example 3

[0062] The preparation process is basically the same as in Example 1, except that the mass fraction of 2-acrylamido-2-methylpropanesulfonic acid in the prepolymer solution prepared in step 2 is 0.9% and the mass fraction of polyethyleneimine is 0.4%. At this time, the molar ratio of 2-acrylamido-2-methylpropanesulfonic acid to polyethyleneimine is 1:0.8. The concentrations of other raw materials are exactly the same as in Example 1.

[0063] Comparative Example 4

[0064] The preparation process is basically the same as in Example 1, except that the mass fraction of 2-acrylamido-2-methylpropanesulfonic acid in the prepolymer solution prepared in step 2 is 0.9% and the mass fraction of polyethyleneimine is 0.6%. At this time, the molar ratio of 2-acrylamido-2-methylpropanesulfonic acid to polyethyleneimine is 1:1.2. The concentrations of other raw materials are exactly the same as in Example 1.

[0065] Figure 1From top to bottom, the images show scanning electron microscope (SEM) images of the surface morphology of the coatings prepared in Example 1, Comparative Example 1, Comparative Example 2, and Comparative Example 4 after immersion in physiological saline for 24 hours. Observation revealed that the surface of the coating prepared in Comparative Example 2 was very uneven, which was confirmed by subsequent swelling tests to be due to significant swelling. The surface of the coating prepared in Comparative Example 4 was unevenly distributed, which was confirmed by subsequent swelling tests to be due to dissolution. The coating prepared in Example 1, after immersion, had a similar surface morphology to the uncoated substrate of Comparative Example 1, showing no cracks, wrinkles, or dissolution.

[0066] Comparative Example 5

[0067] The preparation process is basically the same as in Example 1, except that in step 2, when preparing the prepolymer solution, chitosan (weight average molecular weight of 70,000 Da) is used instead of polyethyleneimine; the mass fraction of chitosan in the prepolymer solution is 2%, and the molar ratio of 2-acrylamido-2-methylpropanesulfonic acid anionic units to chitosan cationic units is 1:1; the concentrations of other raw materials are exactly the same as in Example 1.

[0068] Comparative Example 6

[0069] The preparation process is basically the same as in Example 1, except that in step 2, when preparing the prepolymer solution, 2-methacryloyloxyethyl phosphoric acid choline is used instead of 2-acrylamido-2-methylpropanesulfonic acid; the mass fraction of 2-methacryloyloxyethyl phosphoric acid choline in the prepolymer solution is 1.3%, and the molar ratio of 2-methacryloyloxyethyl phosphoric acid choline to polyethyleneimine is 1:1; the concentrations of other raw materials are exactly the same as in Example 1.

[0070] Comparative Example 7

[0071] The preparation process is basically the same as in Example 1, except that in step 2, when preparing the prepolymer solution, acrylic acid is used instead of 2-acrylamido-2-methylpropanesulfonic acid; the mass fraction of acrylic acid in the prepolymer solution is 0.3%, and the molar ratio of acrylic acid to polyethyleneimine is 1:1; the concentrations of other raw materials are exactly the same as in Example 1.

[0072] Example 2

[0073] The preparation process is basically the same as in Example 1, except that the mass fraction of 2-acrylamido-2-methylpropanesulfonic acid in the prepolymer solution prepared in step 2 is 0.9% and the mass fraction of polyethyleneimine is 0.45%. At this time, the molar ratio of 2-acrylamido-2-methylpropanesulfonic acid to polyethyleneimine is 1:0.9. The concentrations of other raw materials are exactly the same as in Example 1.

[0074] Example 3

[0075] The preparation process is basically the same as in Example 1, except that the mass fraction of 2-acrylamido-2-methylpropanesulfonic acid in the prepolymer solution prepared in step 2 is 0.9%, and the mass fraction of polyethyleneimine is 0.55%. At this time, the molar ratio of 2-acrylamido-2-methylpropanesulfonic acid to polyethyleneimine is 1:1.1. The concentrations of other raw materials are exactly the same as in Example 1.

[0076] Example 4: Gelatin / Poly-2-acryloylamino-2-methyl-1-propanesulfonic acid two-component plugging agent coating

[0077] The preparation process is basically the same as in Example 1, except that the composition of the prepolymer solution prepared in step 2 is different, specifically:

[0078] A prepolymer solution was prepared by mixing gelatin (glue strength 300), 2-acrylamido-2-methylpropanesulfonic acid, 3-(trimethoxysilyl)propyl methacrylate, photoinitiator I2959 with an ethanol / water mixed solution (ethanol to water mass ratio of 1:1) and shaking thoroughly.

[0079] The prepolymer solution contains 10% gelatin by mass and 1% 2-acrylamido-2-methylpropanesulfonic acid by mass. At this point, the molar ratio of the anionic groups of 2-acrylamido-2-methylpropanesulfonic acid to the cationic groups in the gelatin is 1:1, and the prepolymer solution is neutral. The photoinitiator I2959 has a mass fraction of 0.5%, and the propyl 3-(trimethoxysilyl)methacrylate has a mass fraction of 0.5%.

[0080] Performance testing:

[0081] I. Platelet adhesion test:

[0082] Fresh rabbit blood was centrifuged at 1500 rpm for 15 min to collect platelet-rich plasma. 400 μL of platelet-rich plasma was added to the surfaces of the occluders treated in different examples and comparative examples, and the samples were incubated at 37°C for 2 h, followed by washing three times with PBS. The samples were then fixed with 4 wt% glutaraldehyde aqueous solution for 15 min. Finally, the samples were subjected to gradient dehydration using different volume ratios of ethanol / water solution (20%, 40%, 50%, 60%, 70%, 80%, 90%, 100%). The adhesion and activation status of platelets on the dehydrated samples were observed using SEM.

[0083] Figure 2 These are scanning electron microscope (SEM) images of platelet adhesion on the surface of the occluder after treatment in Examples 1(a), 1(b), and 7(c), respectively. Figure 2As can be seen, in Comparative Example 1, the uncoated occluder surface showed dense platelet adhesion, and the platelets had extended pseudopodia, indicating that the platelets were activated and could lead to a severe coagulation reaction. In Comparative Example 7, the coating surface prepared by replacing 2-acrylamido-2-methyl-1-propanesulfonic acid with acrylic acid showed a significant amount of platelet adhesion, indicating that inappropriate monomer selection can affect the coating's anti-platelet adhesion ability and thus its anti-thrombotic ability. In contrast, the occluder in Example 1 with a two-component coating of polyvinylimide / poly2-acrylamido-2-methyl-1-propanesulfonic acid showed no platelet adhesion and would not lead to thrombosis. II. Endothelial Cell Adhesion Test:

[0084] Human umbilical vein endothelial cells were collected, labeled with a red fluorescent live cell dye, and then seeded at a density of 30,000 cells / cm² on the surface of occluders treated in different embodiments or comparative examples. The number of endothelial cells adhering to the cells was counted at three time points: 4h, 24h, and 72h.

[0085] Figure 3 To statistically analyze the number of endothelial cells on the surface of the occluder after treatment with Comparative Example 1 and Examples 1 and 4, respectively, at 4 h, 24 h, and 72 h after seeding, the following data were collected: Figure 3 Statistical analysis shows that the occluders with a two-component coating of polyvinylimide / poly(2-acrylamide-2-methyl-1-propanesulfonic acid) in Example 1 and a two-component coating of gelatin / poly(2-acrylamide-2-methyl-1-propanesulfonic acid) in Example 4 had a higher initial number of endothelial cells adhering to the surface and a better proliferation rate than the uncoated Comparative Example 1. This indicates that the special coating with the special composition prepared on the surface of the occluder in this invention can promote endothelial adhesion and accelerate endothelial cell proliferation.

[0086] Figure 4 The images show laser confocal images of the adhesion state of endothelial cells on the surface of the plugs treated in Example 1(a) and Comparative Example 1(b) after 72 hours of seeding. Observation of the images reveals that the number of endothelial cells adhering to the surface of the coating prepared in Example 1 after 72 hours is significantly greater than that in Comparative Example 1.

[0087] Figure 5 The image shows a laser confocal image of the endothelial cell adhesion state on the surface of the occluder treated in Example 4 after 72 hours of seeding. It was observed that the occluder with a gelatin / poly2-acryloylamino-2-methyl-1-propanesulfonic acid two-component coating prepared in this example had a large number of endothelial cells adhering to the surface and a good proliferation rate.

[0088] III. Coating stability test:

[0089] Swelling degree determination: The prepared coating was dried in an oven at 37℃ for 24 hours, and the dry weight of the coating was measured. Afterwards, the coating was immersed in physiological saline for 24 hours, the coating sample was removed, the surface moisture was wiped off, and the wet weight of the coating was measured.

[0090] Swelling degree=(wet weight-dry weight)*100% / dry weight.

[0091] Table 1 below lists the swelling degree data of the coatings prepared in Examples 1-4 and Comparative Examples 2-7, respectively. A positive swelling degree indicates that the coating is swollen, and a negative value indicates that the coating is dissolved.

[0092] Table 1

[0093]

[0094] Figure 6 The invention also provides bar charts of swelling degree data for the coatings prepared in Examples 1-3 and Comparative Examples 2-7, respectively. It can be concluded that the coatings prepared in each example of the present invention have suitable swelling degree. Inappropriate polymer types, monomer types and inappropriate raw material ratios can lead to severe swelling or dissolution of the coating. At the same time, the addition of siloxane crosslinking agent in the present invention also helps to stabilize the coating.

[0095] The surface coatings of the occluders prepared in different embodiments or comparative examples were marked with red fluorescent dye, and the coating distribution across the entire occluder disk surface was scanned using laser confocal microscopy. Subsequently, simulating a real delivery environment, the occluder was repeatedly rubbed inside the delivery sheath 100 times, and the disk coating state was scanned again using laser confocal microscopy. The coating retention rate after folding was calculated as follows:

[0096] Coating retention rate (%) = (average fluorescence intensity of coating after folding - average fluorescence intensity of coating before folding) / average fluorescence intensity of coating before folding.

[0097] Figure 7 The images show the laser confocal images of the surface coatings of the occluders prepared in Examples 1, 4, and Comparative Example 2 before and after repeated folding (the laser confocal images of the surface coatings before folding in different examples and comparative examples are basically similar, so only one is selected as a representative). It was observed that after repeated folding 100 times, the coatings on the surface of the occluders prepared in Examples 1 and 4 remained intact and basically unchanged; while the coating prepared in Comparative Example 2 showed obvious peeling.

[0098] Figure 8The figure shows the retention rate of the coatings prepared in Examples 1, 4, and Comparative Example 2 after 100 folds. It also indicates that, compared to Comparative Example 2, the preparation processes of Examples 1 and 4 significantly improve the stability of the coatings on the plugging device. This demonstrates that the coating preparation method proposed in this invention can produce stable coatings on the surface of the plugging device.

[0099] The applicant declares that the present invention is illustrated by the above embodiments, but the present invention is not limited to the above detailed methods.

Claims

1. A method for preparing a surface coating of a plug, characterized in that, Includes the following steps: (1) A prepolymer solution is obtained by blending cationic polymer, anionic monomer, siloxane crosslinking agent, photoinitiator and solvent; The cationic polymer is selected from polyethyleneimine or gelatin; The anionic monomer is selected from 2-acrylamido-2-methylpropanesulfonic acid; When the cationic polymer is selected from polyethyleneimine, bioactive peptides also need to be added; The bioactive polypeptide is selected from one or more of the following: acrylic acid-modified RGD, methacrylic acid-modified RGD, acrylic acid-modified REDV, methacrylic acid-modified REDV, acrylic acid-modified IKVAV, methacrylic acid-modified IKVAV, acrylic acid-modified YIGSR, and methacrylic acid-modified YIGSR. The cationic polymer is selected from polyethyleneimine, and the molar ratio of the cationic polymer to the anionic polymer monomer is 0.9~1.1:1; The cationic polymer is selected from gelatin, and the molar ratio of the cationic polymer to the anionic polymer monomer is 1:1; (2) The prepolymer solution is coated on the surface of the pretreated plug, polymerization is initiated by ultraviolet light, and then cured by heating.

2. The method for preparing the surface coating of the plug according to claim 1, characterized in that, In step (1): The weight-average molecular weight of the cationic polymer is 1000~150000 Da; The siloxane crosslinking agent is selected from at least one of 3-(trimethoxysilyl)propyl methacrylate, O-(methacryloyloxyethyl)-N-(triethoxysilylpropyl)carbamate, vinyltriethoxysilane, and vinyltrimethoxysilane. The solvent is selected from a mixture of ethanol and water.

3. The method for preparing the surface coating of the plug according to claim 2, characterized in that, In step (1): Based on the total mass of the prepolymer solution as 100%, the mass fraction of the cationic polymer is 0.1~10%, the mass fraction of 2-acrylamido-2-methylpropanesulfonic acid is 0.1~20%, the mass fraction of the siloxane crosslinking agent is 0.01~1%, and the mass fraction of the photoinitiator is 0.01~1%. If it contains bioactive polypeptides, the mass fraction is 0.01% to 1%, based on the total mass of the prepolymer solution (100%). In the solvent, the mass ratio of ethanol to water is 0.25 to 4:

1.

4. The method for preparing the surface coating of the plug according to claim 1, characterized in that, In step (2): The pretreated plug is an oxygen plasma activated plug; The oxygen plasma activation involves an oxygen plasma generation frequency of 40 kHz to 13.56 MHz and an activation time of 1 to 60 min.

5. The method for preparing the surface coating of the plugging device according to claim 1, characterized in that, In step (2): The coating includes one or more of spin coating, dip coating, and ultrasonic spraying; The polymerization is initiated by ultraviolet light, with an ultraviolet light intensity of 10~200 mW / cm². 2 The UV polymerization time is 1~10 min; The heating and curing process takes place at a temperature of 50~80℃.

6. The method for preparing the surface coating of the plug according to any one of claims 1 to 5, characterized in that, In step (1): Based on the total mass of the prepolymer solution as 100%, the mass fraction of the cationic polymer is 0.1~10%, and the mass fraction of 2-acrylamido-2-methylpropanesulfonic acid is 0.1~10%. The cationic polymer is selected from polyethyleneimine, and the molar ratio of the cationic polymer to the anionic polymer monomer is 1.0~1.1:

1.

7. The method for preparing the surface coating of the plugging device according to claim 6, characterized in that, In step (1): The cationic polymer is selected from polyethyleneimine.

8. A coating prepared on the surface of a plug by the method according to any one of claims 1 to 7.

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