A medical catheter lumen surface hydrophilic coating solution and methods of making and using the same

Abstract

The application discloses a medical catheter inner cavity surface hydrophilic coating solution and a preparation and use method thereof. The medical catheter inner cavity surface hydrophilic coating solution comprises a primer solution and a surface coating solution. The mass ratio of components in the primer solution is as follows: 0.1-5% of a maleic anhydride copolymer derivative, 0.01-0.5 of a ratio of an aqueous polyurethane to the maleic anhydride copolymer derivative, 0.01-0.05% of gamma-butyrolactone, 0.05-1% of a curing agent, and 95-97% of purified water. The mass ratio of components in the surface coating solution is as follows: 0.1-5% of a hydrophilic polymer, 0.05-1% of a crosslinking agent, and 95-97% of purified water. The primer solution and the surface coating solution adopt a heating curing mode, an interpenetrating network structure is formed between the primer coating and the surface coating, the hydrophilic coating has firm adhesion between the medical catheter surface, and the hydrophilic coating has excellent hydrophilic lubricity and biocompatibility, and can be widely applied to hydrophilic lubricating treatment of the medical catheter surface.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a hydrophilic coating solution for the inner cavity surface of a medical catheter and a preparation and use method thereof. Background Art

[0002] Medical catheters, especially medical interventional catheters, need to be treated with a hydrophilic coating on the inner surface of the catheter when entering the human body and / or delivering medical devices, which reduces the resistance to the passage of the device, thereby improving the effect of interventional treatment, alleviating the patient's pain, and improving the prognosis. Cataract is a common visual impairment disease. The main reason is that the natural lens in the eyeball becomes cloudy due to various reasons. Its initial symptoms are not obvious, but as the disease progresses, symptoms such as blurred vision, myopia, and glare will gradually appear. In severe cases, it can lead to complete blindness in patients. Intraocular lens implantation is currently the most effective means of treating cataracts. When cataract patients undergo intraocular lens implantation, the diseased lens is usually first ultrasonically emulsified and removed, and then the intraocular lens is accurately implanted into the eye with the help of a delivery system. The IOL delivery system primarily consists of a housing, a push rod, an inserter, and / or a loading chamber. During implantation, the push rod propels the lens through the conical cavity of the inserter, where it undergoes a series of deformations, including folding and compression, before finally being injected into the patient's eye through the tip of the inserter. The IOL slowly unfolds within the eye, gradually returning to its original form and replacing the natural lens.

[0003] Intraocular lens inserters are typically made of hydrophobic materials such as polypropylene (PP), polyether block copolyamide (Pebax), polyvinyl chloride (PVC), polyethylene (PE), and nylon. These materials, especially polypropylene (PP), are highly inert and have low surface energy, resulting in a generally high coefficient of friction. Even when folded, hydrophobic intraocular lenses (IOLs) cannot pass smoothly through the small diameter of the inserter lumen. The required injection force is extremely high, making injection difficult and potentially causing severe mechanical damage to the IOL. To reduce the friction of the inserter lumen on hydrophobic IOLs, a hydrophilic lubricating coating is typically applied to the inserter lumen to reduce the coefficient of friction. The goal is to minimize the required injection resistance during IOL insertion, ensuring that the IOL remains intact and rapidly deploys after passing through the small-diameter inserter. However, during clinical and preclinical use of hydrophobic IOLs with injection systems, the hydrophilic coating within the inserter lumen often fails to maintain its integrity, resulting in the coating detaching or adhering to the lens surface during IOL injection. More seriously, due to adhesion to the hydrophilic coating, after the intraocular lens has been inside the inserter for a period of time, the lens experiences significant resistance to initial injection, or even fails to initiate, damaging the lens and rendering it ineffective in treating cataracts. Therefore, there is an urgent need to develop a hydrophilic coating solution for the inner lumen of medical catheters, as well as methods for its preparation and use, to address these technical issues.

[0004] In view of this, the present invention is proposed. Summary of the Invention

[0005] The purpose of the present invention is to provide a hydrophilic coating solution for the inner cavity surface of a medical catheter and a preparation and use method thereof, which can provide a medical interventional catheter, especially an artificial lens introduction head, with an excellent hydrophilic lubricating coating on the inner cavity surface, improve the firmness and lubricity of the hydrophilic coating in the introduction head, ensure that the artificial lens advances smoothly during the injection process in the inner cavity of the introduction head, remains intact after passing through the introduction head, and can be quickly deployed in the human eye. It has broad application prospects and is conducive to promotion and application.

[0006] To achieve the above objectives, the present invention provides a hydrophilic coating solution for the inner lumen surface of a medical catheter, comprising a primer solution and a topcoat solution. The mass ratio of the components in the primer solution is: 0.1-5% of a maleic anhydride copolymer derivative, 0.01-0.5 of an aqueous polyurethane and a maleic anhydride copolymer derivative, 0.01-0.05% of γ-butyrolactone, 0.05-1% of a curing agent, and 95-97% of purified water. The mass ratio of the components in the topcoat solution is: 0.1-5% of a hydrophilic polymer, 0.05-1% of a crosslinking agent, and 95-97% of purified water.

[0007] Preferably, the maleic anhydride copolymer derivative is an olefin-maleic anhydride copolymer, an acrylic acid-maleic anhydride copolymer, an alkyl vinyl ether-maleic anhydride copolymer or a styrene-maleic anhydride copolymer.

[0008] Preferably, the curing agent is carboxymethyl cellulose or adipic acid dihydrazide.

[0009] Preferably, the hydrophilic polymer is a mixture of polyvinyl pyrrolidone (PVP) of different molecular weights, a mixture of polyethylene glycol (PEG), a mixture of polyacrylamide (PAM), a mixture of polyvinyl alcohol (PVA), or a mixture of natural polysaccharides and derivatives.

[0010] Preferably, the hydrophilic polymer is a mixture of polyvinyl pyrrolidone (PVP) with different molecular weights, with a molecular weight of 400,000-1,500,000 and a corresponding K value of 60-120.

[0011] Preferably, the cross-linking agent is a multifunctional aziridine compound.

[0012] Preferably, the cross-linking agent is a trifunctional aziridine compound.

[0013] The present invention also provides a method for preparing the hydrophilic coating solution for the inner surface of a medical catheter, comprising the following steps:

[0014] S1: Preparation of primer solution: The aminolyzed or hydrolyzed maleic anhydride copolymer derivative, waterborne polyurethane, γ-butyrolactone, and curing agent are stirred and thoroughly mixed in a purified aqueous solution, and the pH value of the solution is adjusted to 5-7;

[0015] S2: Preparation of surface coating solution: Polyvinyl pyrrolidone powders of different molecular weights, cross-linking agent, and purified water are fully stirred and dissolved.

[0016] Preferably, in S1, the hydrolysis step of the maleic anhydride copolymer derivative is: taking the maleic anhydride copolymer derivative into a flask, adding an excess of sodium hydroxide solution, and reacting at room temperature or under heating conditions until the aqueous solution becomes clear and transparent, indicating that the maleic anhydride has been completely hydrolyzed.

[0017] Preferably, in S1, the step of aminolysis of the maleic anhydride copolymer derivative comprises: placing the maleic anhydride copolymer derivative in a round-bottom flask, introducing ammonia gas into the round-bottom flask through a connecting device, placing the round-bottom flask on a magnetic stirrer and stirring the reaction sufficiently, and when the pressure of the ammonia gas introduced into the round-bottom flask no longer changes, it indicates that the maleic anhydride has been completely aminolyzed.

[0018] The present invention also provides a method for using the hydrophilic coating solution for the inner surface of a medical catheter, comprising the following steps:

[0019] S1: before applying the hydrophilic coating, the inner surface of the medical catheter is activated, wherein the activation treatment is plasma treatment, silane coupling agent treatment, corona treatment or photochemical grafting, preferably plasma treatment or silane coupling agent treatment;

[0020] S2: Apply the primer solution to the inner surface of the catheter by dipping, brushing or spraying, and heat-curing at 80-120°C for 1-6 hours;

[0021] S3: applying the topcoat solution on the inner cavity surface of the catheter with the cured primer solution, heating and curing at 80-120° C. for 1-6 hours to obtain a medical catheter with an inner cavity surface coated with a cross-linked hydrophilic coating.

[0022] Preferably, the material of the medical catheter is a hydrophobic polymer, and the hydrophobic polymer is polypropylene (PP), polyether block polyamide (Pebax), polyvinyl chloride (PVC), polyethylene (PE) or nylon.

[0023] The present invention provides a hydrophilic coating solution for the inner cavity surface of a medical catheter and a preparation and use method thereof, which have the following beneficial effects.

[0024] 1. This invention effectively solves the problem of insufficient firmness of hydrophilic coatings. By adding a waterborne polyurethane and maleic anhydride copolymerized derivative curing system to the primer solution, the bonding between the primer and the substrate is enhanced. Furthermore, hydrogen bonding between the waterborne polyurethane and polyvinylpyrrolidone molecules and cross-linking reactions between the maleic anhydride copolymerized derivative and a trifunctional aziridine compound are established, creating an interpenetrating chemical cross-linking structure between the hydrophilic primer and topcoat, thereby enhancing the bonding between the primer and topcoat.

[0025] 2. The surface coating solution of the present invention uses polyvinyl pyrrolidone of different brands and molecular weights, so that the hydrophilic coating is both hydrophilic and lubricating while also having a certain strength and flexibility, which can play a good cushioning role during the injection of the intraocular lens.

[0026] 3. The hydrophilic coating solution of this invention utilizes a thermal curing method. The addition of γ-butyrolactone to the primer solution allows for more complete molecular reaction within the coating solution, thereby regulating the molecular structure. The coating surface is non-sticky, and even if the crystal remains in the insert for a period of time before being restarted, it will not experience any jamming issues.

[0027] 4. The hydrophilic coating solution of the present invention is an aqueous solution system, which avoids the corrosion of the catheter by organic solvents, is more environmentally friendly, and has good biocompatibility. DETAILED DESCRIPTION

[0028] The present invention will be further described below with reference to specific embodiments to facilitate understanding of the present invention.

[0029] The present invention provides a hydrophilic coating solution for the inner cavity surface of a medical catheter, comprising a primer solution and a topcoat solution. The mass ratio of the components in the primer solution is: 0.1-5% of a maleic anhydride copolymer derivative, 0.01-0.5% of an aqueous polyurethane and a maleic anhydride copolymer derivative, 0.01-0.05% of gamma-butyrolactone, 0.05-1% of a curing agent, and 95-97% of purified water. The mass ratio of the components in the topcoat solution is: 0.1-5% of a hydrophilic polymer, 0.05-1% of a crosslinking agent, and 95-97% of purified water.

[0030] Preferably, the maleic anhydride copolymer derivative is an olefin-maleic anhydride copolymer, an acrylic acid-maleic anhydride copolymer, an alkyl vinyl ether-maleic anhydride copolymer or a styrene-maleic anhydride copolymer. In the primer solution, a maleic anhydride copolymer derivative with good substrate bonding, high activity and water solubility is selected. The maleic anhydride molecule contains a double bond and two carbonyl groups. The double bond has a strong electron-deficient property due to the electron-withdrawing effect of the carbonyl group, which enables maleic anhydride to form alternating copolymers with many electron-rich monomers to generate olefin-maleic anhydride copolymers, acrylic acid-maleic anhydride copolymers, alkyl vinyl ether-maleic anhydride copolymers, styrene-maleic anhydride copolymers, etc. The anhydride group in the maleic anhydride can undergo many organic reactions, such as esterification, amidation, and reactions such as acid-base neutralization with alkali.

[0031] Preferably, the curing agent is carboxymethyl cellulose or adipic acid dihydrazide.

[0032] In the present invention, the primer solution is water-soluble hydroxymethyl cellulose or adipic acid dihydrazide. The hydroxyl groups in the hydroxymethyl cellulose and the amino groups in the adipic acid dihydrazide can be cured and cross-linked with the carboxylic acid groups generated by the reaction of the maleic anhydride copolymer derivative.

[0033] In the present invention, a small amount of water-based polyurethane is added to the primer solution. On the one hand, the water-based polyurethane has a strong bonding force with the inner surface of the medical catheter. On the other hand, the water-based polyurethane can continue to react with the top coating solution to form a cross-linked network structure.

[0034] In the present invention, γ-butyrolactone is further added to the primer solution to make the reaction more complete during the thermal curing process.

[0035] Preferably, the hydrophilic polymer is a mixture of polyvinyl pyrrolidone (PVP) of different molecular weights, a mixture of polyethylene glycol (PEG), a mixture of polyacrylamide (PAM), a mixture of polyvinyl alcohol (PVA), or a mixture of natural polysaccharides and derivatives.

[0036] Preferably, the hydrophilic polymer is a mixture of polyvinyl pyrrolidone (PVP) with different molecular weights, with a molecular weight of 400,000-1,500,000 and a corresponding K value of 60-120.

[0037] Preferably, the cross-linking agent is a multifunctional aziridine compound.

[0038] Preferably, the cross-linking agent is a trifunctional aziridine compound.

[0039] The surface coating solution of the present invention utilizes a hydrophilic polymer, polyvinylpyrrolidone (PVP), and a trifunctional aziridine crosslinker. The trifunctional aziridine reacts with the carboxylic acid groups in the maleic anhydride copolymer derivative in the primer to form a crosslinked structure. The amine groups in the hydrophilic polyurethane in the primer also form hydrogen bonds with the carbonyl groups in the PVP. This creates strong interactions between the PVP molecular chains, the maleic anhydride copolymer derivative, and the waterborne polyurethane, thereby enhancing the coating's durability. Polyvinylpyrrolidone (PVP) contains a highly polar lactam group in its molecular structure, exhibiting excellent hydrophilicity. Upon contact with water, it rapidly absorbs water molecules, which form a hydrogel through hydrogen bonding, giving the PVP coating strong lubricity. Furthermore, PVP exhibits excellent biological inertness and is not involved in human metabolism, resulting in excellent biocompatibility. The PVP hydrophilic coating on medical device surfaces must also possess a certain degree of hardness and softness. High-molecular-weight PVP is hard and brittle, making it less effective as a cushion. Low-molecular-weight PVP is too soft and lacks firmness, making the coating prone to peeling. Therefore, the hydrophilic polymers used in this invention utilize polyvinylpyrrolidone (PVP) of varying molecular weights, resulting in a hydrophilic coating that combines the hardness of high-molecular-weight PVP with the flexibility of low-molecular-weight PVP.

[0040] The present invention also provides a method for preparing the hydrophilic coating solution for the inner surface of a medical catheter, comprising the following steps:

[0041] S1: Preparation of primer solution: The aminolyzed or hydrolyzed maleic anhydride copolymer derivative, waterborne polyurethane, γ-butyrolactone, and curing agent are stirred and thoroughly mixed in a purified aqueous solution, and the pH value of the solution is adjusted to 5-7;

[0042] S2: Preparation of surface coating solution: Polyvinyl pyrrolidone powders of different molecular weights, cross-linking agent, and purified water are fully stirred and dissolved.

[0043] Preferably, in S1, the hydrolysis step of the maleic anhydride copolymer derivative is: taking the maleic anhydride copolymer derivative into a flask, adding an excess of sodium hydroxide solution, and reacting at room temperature or under heating conditions until the aqueous solution becomes clear and transparent, indicating that the maleic anhydride has been completely hydrolyzed.

[0044] Preferably, in S1, the step of aminolysis of the maleic anhydride copolymer derivative comprises: placing the maleic anhydride copolymer derivative in a round-bottom flask, introducing ammonia gas into the round-bottom flask through a connecting device, placing the round-bottom flask on a magnetic stirrer and stirring the reaction sufficiently, and when the pressure of the ammonia gas introduced into the round-bottom flask no longer changes, it indicates that the maleic anhydride has been completely aminolyzed.

[0045] In the present invention, the maleic anhydride copolymer derivative undergoes amidation and hydrolysis modification to generate more carboxylic acid groups, increasing reactivity and facilitating crosslinking and curing with a curing agent. The maleic anhydride copolymer derivative undergoes a gas-solid phase reaction with ammonia (NH3) to produce amic acid, which further reacts in an acidic solution to form amide bonds and carboxylic acid groups. The anhydride units in the maleic anhydride copolymer derivative can be completely hydrolyzed in aqueous sodium hydroxide solution. By adjusting the pH to an acidic environment, the anhydride units gradually convert to carboxylic acid groups. The carboxylic acid groups increase the copolymer's solubility in water and can also react with other groups for crosslinking.

[0046] The present invention also provides a method for using the hydrophilic coating solution for the inner surface of a medical catheter, comprising the following steps:

[0047] S1: before applying the hydrophilic coating, the inner surface of the medical catheter is activated, wherein the activation treatment is plasma treatment, silane coupling agent treatment, corona treatment or photochemical grafting, preferably plasma treatment or silane coupling agent treatment;

[0048] S2: Apply the primer solution to the inner surface of the catheter by dipping, brushing or spraying, and heat-curing at 80-120°C for 1-6 hours;

[0049] S3: applying the topcoat solution on the inner cavity surface of the catheter with the cured primer solution, heating and curing at 80-120° C. for 1-6 hours to obtain a medical catheter with an inner cavity surface coated with a cross-linked hydrophilic coating.

[0050] Preferably, the material of the medical catheter is a hydrophobic polymer, and the hydrophobic polymer is polypropylene (PP), polyether block polyamide (Pebax), polyvinyl chloride (PVC), polyethylene (PE) or nylon. Example 1

[0051] Place 1 g of styrene-maleic anhydride in a 250 mL round-bottom flask. Bubble ammonia gas into a balloon until the balloon is fully inflated. Connect the balloon to a needle and insert it into the round-bottom flask through a rubber stopper. Place the round-bottom flask on a magnetic stirrer and stir thoroughly until the balloon volume stabilizes after a period of ammonia gas flow, indicating complete aminolysis of the maleic anhydride. Add deionized water to the flask and sonicate until clear and transparent. Adjust the pH to acidic to prepare a 1% by weight solution. Add adipic acid dihydrazide to a 0.1% by weight concentration in the aqueous solution. Then, add 0.1 g of a commercially available hydrophilic polyurethane and 0.01 g of gamma-butyrolactone. Stir thoroughly until completely homogeneous to prepare a hydrophilic coating solution and primer solution.

[0052] 1 g of K90 PVP and 0.5 g of K120 PVP were dissolved in 150 g of purified water, and 0.2 g of a trifunctional aziridine compound as a crosslinking agent was added thereto to prepare a hydrophilic coating surface coating solution with a mass fraction of 1%.

[0053] Take the intraocular lens introduction head, use the primer coating method to drip the hydrophilic coating primer solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 3 hours, and take it out; drip the hydrophilic coating topcoat solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 3 hours, and take it out; obtain the hydrophilic coating intraocular lens introduction head.

[0054] A +20.0-degree intraocular lens was obtained and folded using lens forceps. The lens was then placed into the inserter, which was then connected to the pusher. After the lens had been in the inserter for 3 minutes, the lens was injected. The results of the lens injection are shown in Table 1. Example 2

[0055] Place 1 g of PSMA in a 250 mL flask, add an excess of sodium hydroxide, and react at room temperature for 1 hour. After the polymer is completely hydrolyzed and the aqueous solution becomes clear and transparent, add dilute hydrochloric acid to adjust the pH to 5 to retain some carboxylic acid in the system. Prepare a 1% by weight aqueous solution. Add hydroxymethyl cellulose to the system to a 0.1% by weight fraction. Then, add 0.1 g of commercially available hydrophilic polyurethane and 0.01 g of gamma-butyrolactone to create a hydrophilic coating solution and primer solution.

[0056] 0.5 g of K90 PVP and 1 g of K120 PVP were dissolved in 150 g of purified water, and 0.2 g of a trifunctional aziridine compound as a crosslinking agent was added thereto to prepare a hydrophilic coating surface coating solution with a mass fraction of 1%.

[0057] Take the intraocular lens introduction head, use the primer coating method to drip the hydrophilic coating primer solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 5 hours, and take it out; drip the hydrophilic coating topcoat solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 5 hours, and take it out; obtain the hydrophilic coating intraocular lens introduction head.

[0058] A +20.0-degree intraocular lens was obtained and folded using lens forceps. The lens was then placed into the inserter, which was then connected to the pusher. After the lens had been in the inserter for 3 minutes, the lens was injected. The results of the lens injection are shown in Table 1. Example 3

[0059] Place 1 g of PSMA in a 250 mL flask, add an excess of sodium hydroxide, and react at room temperature for 1 hour. After the polymer is completely hydrolyzed and the aqueous solution becomes clear and transparent, add dilute hydrochloric acid to adjust the pH to 5 to retain some carboxylic acid in the system. Prepare a 5% by weight aqueous solution. Add hydroxymethyl cellulose to the system to a 0.1% by weight fraction in the aqueous solution. Then, add 0.1 g of commercially available hydrophilic polyurethane and 0.01 g of gamma-butyrolactone to prepare a hydrophilic coating solution or primer solution.

[0060] 1.5 g of K90 PVP and 3 g of K120 PVP were dissolved in 150 g of purified water, and 0.5 g of a trifunctional aziridine compound as a crosslinking agent was added thereto to prepare a hydrophilic coating surface coating solution with a mass fraction of 3%.

[0061] Take the intraocular lens inserter and, using a primer coating method, drip a hydrophilic coating primer solution into the inserter cavity. Shake the solution up and down to evenly cure it. Place it in an oven at 120°C for 6 hours and remove it. Then, drip a hydrophilic coating topcoat solution into the inserter cavity. Shake the solution up and down to evenly cure it. Place it in an oven at 120°C for 6 hours and remove it. This yields a hydrophilic-coated intraocular lens inserter. (This example primarily increases the solution concentration and prolongs the curing time.)

[0062] A +20.0-degree intraocular lens was obtained and folded using lens forceps. The lens was then placed into the inserter, which was then connected to the pusher. After the lens had been in the inserter for 3 minutes, the lens was injected. The results of the lens injection are shown in Table 1.

[0063] Comparative Example 1:

[0064] Take 1.5g of commercially available hydrophilic polyurethane to prepare a solution with a mass fraction of 1%, add adipic acid dihydrazide, whose mass fraction in the aqueous solution is 0.1%, and then add 0.01g of gamma-butyrolactone. Stir thoroughly until completely uniform to prepare a hydrophilic coating solution and a primer solution.

[0065] Dissolve 1g of K90 PVP and 0.5g of K120 PVP in 150g of purified water. Add 0.2g of a trifunctional aziridine compound as a crosslinker to create a 1% hydrophilic coating solution. (This comparative example does not contain the maleic anhydride copolymer.)

[0066] Take the intraocular lens introduction head, use the primer coating method to drip the hydrophilic coating primer solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 3 hours, and take it out; drip the hydrophilic coating topcoat solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 3 hours, and take it out; obtain the hydrophilic coating intraocular lens introduction head.

[0067] A +20.0-degree intraocular lens was obtained and folded using lens forceps. The lens was then placed into the inserter, which was then connected to the pusher. After the lens had been in the inserter for 3 minutes, the lens was injected. The results of the lens injection are shown in Table 1.

[0068] Comparative Example 2:

[0069] Place 1 g of PSMA in a 250 mL flask, add an excess of sodium hydroxide, and react at room temperature for 1 hour. After the polymer is completely hydrolyzed and the aqueous solution becomes clear and transparent, add dilute hydrochloric acid to adjust the pH to 5 to retain some carboxylic acid in the system. Prepare a 1% by weight aqueous solution. Add hydroxymethyl cellulose to the system to a 0.1% by weight fraction. Then, add 0.1 g of commercially available hydrophilic polyurethane and 0.01 g of gamma-butyrolactone to create a hydrophilic coating solution and primer solution.

[0070] Dissolve 3.0g of K120 PVP in 150g of purified water and add 0.2g of a trifunctional aziridine compound as a crosslinker to create a 2% hydrophilic coating solution. (This comparative example primarily uses a single K-value PVP.)

[0071] Take the intraocular lens introduction head, use the primer coating method to drip the hydrophilic coating primer solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 5 hours, and take it out; drip the hydrophilic coating topcoat solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 5 hours, and take it out; obtain the hydrophilic coating intraocular lens introduction head.

[0072] A +20.0-degree intraocular lens was obtained and folded using lens forceps. The lens was then placed into the inserter, which was then connected to the pusher. After the lens had been in the inserter for 3 minutes, the lens was injected. The results of the lens injection are shown in Table 1.

[0073] Comparative Example 3:

[0074] Place 1 g of PSMA in a 250 mL flask, add an excess of sodium hydroxide, and react at room temperature for 1 hour. After the polymer is completely hydrolyzed and the aqueous solution becomes clear and transparent, add dilute hydrochloric acid to adjust the pH to 5 to retain some carboxylic acid in the system. Prepare aqueous solutions with a mass fraction of 5% for each. Add hydroxymethyl cellulose to the system to a mass fraction of 0.1% in the aqueous solution. Then, add 0.1 g of a commercially available hydrophilic polyurethane to prepare a hydrophilic coating solution or primer solution.

[0075] 1.5 g of K90 PVP and 3 g of K120 PVP were dissolved in 150 g of purified water, and 0.5 g of a trifunctional aziridine compound as a crosslinking agent was added thereto to prepare a hydrophilic coating surface coating solution with a mass fraction of 3%.

[0076] Take the intraocular lens inserter and, using a primer coating method, drip a hydrophilic coating primer solution into the inserter cavity. Shake it up and down to evenly cure it. Place it in an oven at 120°C for 1 hour and remove it. Then, drip a hydrophilic coating topcoat solution into the inserter cavity. Shake it up and down to evenly cure it. Place it in an oven at 120°C for 1 hour and remove it. This yields a hydrophilic-coated intraocular lens inserter. (This comparative example does not include gamma-butyrolactone and reduces the curing time.)

[0077] A +20.0-degree intraocular lens was obtained and folded using lens forceps. The lens was then placed into the inserter, which was then connected to the pusher. After the lens had been in the inserter for 3 minutes, the lens was injected. The results of the lens injection are shown in Table 1.

[0078] Table 1 Results of intraocular lens bolus injection

[0079]

[0080] As can be seen from Table 1: By comparing Comparative Example 1 with Example 1, it is shown that the present invention effectively solves the problem of insufficient firmness of the hydrophilic coating. By adding a water-based polyurethane and a maleic anhydride copolymer derivative curing system to the primer solution, the bonding force between the primer and the substrate is enhanced; hydrogen bonding between the water-based polyurethane and polyvinyl pyrrolidone molecules, and a cross-linking reaction between the maleic anhydride copolymer derivative and the trifunctional aziridine compound are constructed, and an interpenetrating chemical cross-linking structure is constructed between the hydrophilic coating primer and the topcoat, thereby enhancing the bonding force between the primer and the topcoat.

[0081] By comparing Comparative Example 2 with Example 2, it is shown that different brands of polyvinyl pyrrolidone corresponding to different molecular weights are used in the surface coating solution of the present invention, so that the hydrophilic coating is both hydrophilic and lubricating, and has a certain strength and flexibility, which can play a good cushioning role when injecting artificial lenses.

[0082] By comparing Comparative Example 3 with Example 3, it is shown that the hydrophilic coating solution of the present invention adopts a fully thermally cured method, and the addition of γ-butyrolactone in the primer solution makes the molecules in the coating solution react more fully, thereby achieving the purpose of regulating the molecular structure. The coating surface is not sticky, and even if the crystal stays in the introduction head for a period of time and then starts, there will be no jamming problem.

[0083] This document uses specific examples to illustrate the inventive concept in detail. The above embodiments are only intended to help understand the core concept of the present invention. It should be noted that any obvious modifications, equivalent substitutions, or other improvements made by a person skilled in the art without departing from the inventive concept should be included within the scope of protection of the present invention.

Claims

1. A hydrophilic coating solution for the inner surface of a medical catheter, characterized in that: The invention comprises a primer solution and a top coating solution. The mass ratio of the components in the primer solution is: 0.1-5% of a maleic anhydride copolymer derivative, 0.01-0.5 of an aqueous polyurethane and a maleic anhydride copolymer derivative, 0.01-0.05% of γ-butyrolactone, 0.05-1% of a curing agent, and 95-97% of purified water. The mass ratio of the components in the top coating solution is: 0.1-5% of a hydrophilic polymer, 0.05-1% of a crosslinking agent, and 95-97% of purified water. The hydrophilic polymer is a mixture of high-molecular-weight and low-molecular-weight polyvinyl pyrrolidone, with a molecular weight of 400,000-1,500,000 and a corresponding K value of 60-120.

2. The hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 1, characterized in that: The maleic anhydride copolymer derivative is an olefin-maleic anhydride copolymer, an acrylic acid-maleic anhydride copolymer, an alkyl vinyl ether-maleic anhydride copolymer or a styrene-maleic anhydride copolymer.

3. The hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 2, characterized in that: The curing agent is carboxymethyl cellulose or adipic acid dihydrazide.

4. The hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 3, characterized in that: The cross-linking agent is a multifunctional aziridine compound.

5. A method for preparing a hydrophilic coating solution for the inner cavity surface of a medical catheter according to any one of claims 1 to 4, characterized in that: The steps include: S1: Preparation of primer solution: The aminolyzed or hydrolyzed maleic anhydride copolymer derivative, waterborne polyurethane, γ-butyrolactone, and curing agent are stirred and thoroughly mixed in a purified aqueous solution, and the pH value of the solution is adjusted to 5-7; S2: Preparation of surface coating solution: Polyvinyl pyrrolidone powders of different molecular weights, cross-linking agent, and purified water are fully stirred and dissolved.

6. The method for preparing a hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 5, characterized in that: In S1, the hydrolysis step of the maleic anhydride copolymer derivative is as follows: taking the maleic anhydride copolymer derivative into a flask, adding an excess amount of sodium hydroxide solution, and reacting at room temperature or under heating conditions until the aqueous solution becomes clear and transparent, indicating that the maleic anhydride has been completely hydrolyzed.

7. The method for preparing a hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 6, characterized in that: In S1, the step of aminolysis of the maleic anhydride copolymer derivative is as follows: placing the maleic anhydride copolymer derivative in a round-bottom flask, introducing ammonia gas into the round-bottom flask through a connecting device, placing the round-bottom flask on a magnetic stirrer and stirring the reaction sufficiently, and when the pressure of the ammonia gas introduced into the round-bottom flask no longer changes, it indicates that the maleic anhydride has been completely aminolyzed.

8. A method for using the hydrophilic coating solution for the inner cavity surface of a medical catheter according to any one of claims 1 to 4, characterized in that: The steps include: S1: before applying the hydrophilic coating, the inner surface of the medical catheter is activated, wherein the activation treatment is plasma treatment, silane coupling agent treatment, corona treatment or photochemical grafting; S2: Apply the primer solution to the inner surface of the catheter by dipping, brushing or spraying, and heat-curing at 80-120°C for 1-6 hours; S3: applying the topcoat solution on the inner cavity surface of the catheter with the cured primer solution, heating and curing at 80-120° C. for 1-6 hours to obtain a medical catheter with an inner cavity surface coated with a cross-linked hydrophilic coating.

9. The method for using a hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 8, characterized in that: The material of the medical catheter is a hydrophobic polymer, and the hydrophobic polymer is polypropylene (PP), polyether block polyamide (Pebax), polyvinyl chloride (PVC), polyethylene (PE) or nylon.

Images