Hydrophilic coating solution for inner cavity surface of medical catheter as well as preparation method and use method of hydrophilic coating solution

Abstract

The invention 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 base coating solution and a surface coating solution, and the base coating solution comprises, by mass, 0.1-5% of maleic anhydride copolymer derivatives, 0.1-5% of a surfactant, 0.1-5% of a pH regulator and the balance deionized water. The proportion of the waterborne polyurethane and maleic anhydride copolymer derivative is 0.01-0.5, the proportion of the gamma-butyrolactone is 0.01-0.05%, the proportion of the curing agent is 0.05-1% and the proportion of the purified water is 95-97%, the mass ratio of the hydrophilic polymer in the surface coating solution is 0.1-5%, the mass ratio of the cross-linking agent in the surface coating solution is 0.05-1% and the mass ratio of the purified water in the surface coating solution is 95-97%, and the base coating solution and the surface coating solution are in a heating curing mode. An interpenetrating network structure is formed between the bottom coating and the surface coating, firm adhesive force exists between the hydrophilic coating and the surface of the medical catheter, meanwhile, excellent hydrophilic lubricity and biocompatibility are achieved, and the hydrophilic lubricating coating can be widely applied to hydrophilic lubricating treatment of the surface of the medical catheter.

Description

Technical Field

[0001] The 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 pain of patients, and improving 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 cause complete blindness in patients. Artificial lens implantation is currently the most effective means of treating cataracts. When cataract patients undergo artificial lens implantation, they usually first remove the diseased lens through ultrasonic emulsification, and then use the delivery system to accurately implant the artificial lens into the eye. The structure of the intraocular lens delivery system mainly includes a shell, a push rod, an introduction head and / or a loading chamber. During the lens implantation process, the push rod pushes the lens forward in the conical inner cavity of the introduction head. The intraocular lens undergoes deformation processes such as folding and compression, and is finally injected into the patient's eye through the top of the introduction head. The intraocular lens slowly unfolds in the eye and gradually returns to its original shape, thus replacing the natural lens.

[0003] The material of the intraocular lens introduction head is generally hydrophobic materials such as polypropylene PP, polyether block copolyamide Pebax, polyvinyl chloride PVC, polyethylene PE, nylon, etc. These materials, especially polypropylene PP, are highly inert, have low surface energy, and generally have a high friction coefficient. Even when the hydrophobic intraocular lens is folded, it cannot pass smoothly through the small diameter intracavity port of the introduction head. The required injection force is very large, the injection is difficult, and it is very easy to cause serious mechanical damage to the intraocular lens. In order to reduce the friction force of the intracavity of the introduction head on the hydrophobic intraocular lens, it is generally achieved by preparing a hydrophilic lubricating coating on the surface of the intracavity of the introduction head to reduce the friction coefficient. The goal is to reduce the injection resistance required when the intraocular lens is injected into the introduction head, and the intraocular lens remains intact and can be quickly deployed after passing through the small-caliber introduction head. However, in the clinical and preclinical use of hydrophobic intraocular lenses in conjunction with the injection system, the hydrophilic coating in the introduction head is often not firm enough, and the coating falls off or sticks to the surface of the lens during the injection of the intraocular lens. More seriously, due to reasons such as adhesion to the hydrophilic coating, when the intraocular lens stays in the introduction head for a period of time, the lens has a large resistance to injection and even cannot be started, and the lens is damaged, thus losing its original function of treating cataract patients. Therefore, it is urgent to develop a hydrophilic coating solution for the inner cavity surface of a medical catheter and a preparation and use method thereof to solve the above technical problems.

[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 impart an excellent hydrophilic lubricating coating to the inner cavity surface of a medical interventional catheter, especially an artificial lens introduction head, and improve the firmness and lubricity of the hydrophilic coating in the introduction head, thereby ensuring that the artificial lens moves forward smoothly during the push 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. The present invention has broad application prospects and is conducive to popularization and application.

[0006] In order to achieve the above-mentioned object, the present invention provides a hydrophilic coating solution for the inner cavity surface of a medical catheter, comprising a primer solution and a surface coating solution, wherein 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 to 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 surface coating solution is: 0.1-5% of a hydrophilic polymer, 0.05-1% of a cross-linking 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) with 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 cavity surface of a medical catheter, comprising the following steps: S1: Preparation of primer solution: The aminolyzed or hydrolyzed maleic anhydride copolymer derivative, waterborne polyurethane, γ-butyrolactone and curing agent are stirred and fully 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, crosslinking agent, and purified water solution are fully stirred and dissolved.

[0014] 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.

[0015] Preferably, in S1, the step of aminolysis of the maleic anhydride copolymer derivative is: taking the maleic anhydride copolymer derivative into a round-bottom flask, passing ammonia gas into the round-bottom flask through a connecting device, placing the round-bottom flask on a magnetic stirrer to fully stir the reaction, and when the pressure of the ammonia gas passed into the round-bottom flask no longer changes, it indicates that the maleic anhydride has been completely aminolyzed.

[0016] The present invention also provides a method for using the hydrophilic coating solution for the inner cavity surface of a medical catheter, comprising the following steps: S1: before the hydrophilic coating treatment, the inner cavity 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; S2: Apply the primer solution to the inner surface of the catheter by dipping, brushing or spraying, and heat and cure at 80-120° C. for 1-6 hours; S3: applying the top coating 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.

[0017] 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.

[0018] 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.

[0019] 1. 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 into the primer solution, the bonding force between the primer and the substrate is enhanced; hydrogen bonding between water-based polyurethane and polyvinyl pyrrolidone molecules, and cross-linking reactions between maleic anhydride copolymer derivatives and trifunctional aziridine compounds are constructed, and an interpenetrating chemical cross-linking structure is constructed between the hydrophilic coating primer and the surface coating, thereby enhancing the bonding force between the primer and the surface coating.

[0020] 2. The surface coating solution of the present invention uses polyvinyl pyrrolidone of different brands and corresponding molecular weights, so that the hydrophilic coating is both hydrophilic and lubricating, and has a certain strength and flexibility, and can play a good cushioning role when the intraocular lens is injected.

[0021] 3. The hydrophilic coating solution of the present invention adopts a thermal curing method. γ-butyrolactone is added to the primer solution to make 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.

[0022] 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

[0023] The present invention is further described below in conjunction with specific embodiments to help understand the content of the present invention.

[0024] The invention provides a hydrophilic coating solution for the inner cavity surface of a medical catheter, comprising a primer solution and a surface 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 to 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 surface coating solution is: 0.1-5% of a hydrophilic polymer, 0.05-1% of a cross-linking agent, and 95-97% of purified water.

[0025] 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 bonding to the substrate, high activity and water solubility is selected. The maleic anhydride molecule contains a double bond and two carbonyl groups, and 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 maleic anhydride can undergo many organic reactions, such as esterification, amidation, and acid-base neutralization reactions with alkali.

[0026] Preferably, the curing agent is carboxymethyl cellulose or adipic acid dihydrazide.

[0027] In the present invention, the primer solution is water-soluble hydroxymethyl cellulose or adipic acid dihydrazide, and the hydroxyl groups in the hydroxymethyl cellulose and the amine 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.

[0028] 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 surface coating solution to form a cross-linked network structure.

[0029] In the present invention, γ-butyrolactone is also added to the primer solution to make the reaction more complete during the thermal curing process.

[0030] Preferably, the hydrophilic polymer is a mixture of polyvinyl pyrrolidone (PVP) with 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.

[0031] 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.

[0032] Preferably, the cross-linking agent is a multifunctional aziridine compound.

[0033] Preferably, the cross-linking agent is a trifunctional aziridine compound.

[0034] The surface coating solution of the present invention selects a hydrophilic polymer polyvinyl pyrrolidone (PVP) and a cross-linking agent trifunctional aziridine compound. The trifunctional aziridine compound can react with the carboxylic acid group in the maleic anhydride copolymer derivative in the primer to generate a cross-linked structure; the amine group in the hydrophilic polyurethane in the primer can also generate a hydrogen bond structure with the carbonyl group in PVP. A strong force is formed between the PVP molecular chain, the maleic anhydride copolymer derivative and the waterborne polyurethane, thereby improving the firmness of the coating. Polyvinyl pyrrolidone (PVP) contains a lactam group with a large polarity in its molecular structure, has good hydrophilicity, and will quickly absorb water when it meets water. The water molecules form a hydrogel through hydrogen bond complexation, so that the PVP coating has strong lubricity; at the same time, PVP has excellent biological inertness, does not participate in human metabolism, and has good biocompatibility. The PVP hydrophilic coating on the surface of medical equipment should also have a certain degree of hardness and softness. The PVP with a large molecular weight has a high hardness and is "brittle", and the cushioning effect is not obvious; the PVP with a small molecular weight is too soft and has a low firmness, and the coating is easy to fall off. Therefore, the hydrophilic polymer in the present invention selects polyvinyl pyrrolidone (PVP) with different molecular weights, so that the hydrophilic coating has both the hardness of the large molecular weight PVP and the flexibility of the small molecular weight PVP.

[0035] The present invention also provides a method for preparing the hydrophilic coating solution for the inner cavity surface of a medical catheter, comprising the following steps: S1: Preparation of primer solution: The aminolyzed or hydrolyzed maleic anhydride copolymer derivative, waterborne polyurethane, γ-butyrolactone and curing agent are stirred and fully 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, crosslinking agent, and purified water solution are fully stirred and dissolved.

[0036] 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.

[0037] Preferably, in S1, the step of aminolysis of the maleic anhydride copolymer derivative is: taking the maleic anhydride copolymer derivative into a round-bottom flask, passing ammonia gas into the round-bottom flask through a connecting device, placing the round-bottom flask on a magnetic stirrer to fully stir the reaction, and when the pressure of the ammonia gas passed into the round-bottom flask no longer changes, it indicates that the maleic anhydride has been completely aminolyzed.

[0038] In the present invention, the maleic anhydride copolymer derivative is subjected to amidation modification and hydrolysis modification to generate more carboxylic acid groups, increase the reaction activity, and facilitate crosslinking and curing with a curing agent. The maleic anhydride copolymer derivative reacts with ammonia (NH3) in a gas-solid phase to generate amide acid, which further reacts in an acidic solution to generate amide bonds and carboxylic acid groups; the anhydride units in the maleic anhydride copolymer derivative can be completely hydrolyzed in a sodium hydroxide aqueous solution, and the solution is made acidic by adjusting the pH, and the anhydride units are gradually converted into carboxylic acid groups. The carboxylic acid group increases the solubility of the copolymer in water and can also react with other groups for crosslinking.

[0039] The present invention also provides a method for using the hydrophilic coating solution for the inner cavity surface of a medical catheter, comprising the following steps: S1: before the hydrophilic coating treatment, the inner cavity 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; S2: Apply the primer solution to the inner surface of the catheter by dipping, brushing or spraying, and heat and cure at 80-120° C. for 1-6 hours; S3: applying the top coating 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.

[0040] 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. Embodiment 1:

[0041] Take 1 g of styrene-maleic anhydride in a 250 mL round-bottom flask, pass ammonia into the balloon until the balloon is completely inflated, then connect the balloon to the needle and insert it into the round-bottom flask through a rubber stopper. Place the round-bottom flask on a magnetic stirrer and stir the reaction thoroughly until the volume of the balloon does not change after ammonia is passed through for a period of time, indicating that the maleic anhydride has been completely aminolyzed. Add deionized water to the flask, sonicate until clear and transparent, adjust the pH to acidic, prepare a solution with a mass fraction of 1%, add adipic acid dihydrazide, and its mass fraction in the aqueous solution is 0.1%. Then add 0.1g of commercially available hydrophilic polyurethane and 0.01g of γ-butyrolactone, stir thoroughly until completely uniform, and prepare a hydrophilic coating solution and primer solution.

[0042] 1 g of PVP with a brand number of K90 and 0.5 g of PVP with a brand number of K120 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%.

[0043] Take the intraocular lens introduction head, drip the hydrophilic coating primer solution into the inner cavity of the introduction head by primer coating, 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 top coating 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.

[0044] Take a +20.0 degree intraocular lens, fold it with lens forceps and put it into the introduction head, and connect the introduction head to the pusher. After the intraocular lens is placed in the introduction head for 3 minutes, push the lens. The results of the lens push are shown in Table 1. Embodiment 2:

[0045] Take 1 g of PSMA in a 250 mL flask, add excess sodium hydroxide, react at room temperature for 1 h, and after the polymer is completely hydrolyzed and the aqueous solution is clear and transparent, add dilute hydrochloric acid to adjust the pH to 5, so that a part of the carboxylic acid is retained in the system, and prepare an aqueous solution with a mass fraction of 1%. Add hydroxymethyl cellulose to the system, and its mass fraction in the aqueous solution is 0.1%. Then add 0.1 g of commercially available hydrophilic polyurethane and 0.01 g of γ-butyrolactone to prepare a hydrophilic coating solution and a primer solution.

[0046] 0.5 g of PVP with a brand number of K90 and 1 g of PVP with a brand number of K120 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%.

[0047] Take the intraocular lens introduction head, drip the hydrophilic coating primer solution into the inner cavity of the introduction head by primer coating, 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 top coating solution into the inner cavity of the introduction head again, 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.

[0048] Take a +20.0 degree intraocular lens, fold it with lens forceps and put it into the introduction head, and connect the introduction head to the pusher. After the intraocular lens is placed in the introduction head for 3 minutes, push the lens. The results of the lens push are shown in Table 1. Embodiment 3:

[0049] Take 1 g of PSMA in a 250 mL flask, add excess sodium hydroxide, react at room temperature for 1 h, and after the polymer is completely hydrolyzed and the aqueous solution is clear and transparent, add dilute hydrochloric acid to adjust the pH to 5, so that a part of the carboxylic acid is retained in the system, and prepare an aqueous solution with a mass fraction of 5%. Add hydroxymethyl cellulose to the system, and its mass fraction in the aqueous solution is 0.1%. Then add 0.1 g of commercially available hydrophilic polyurethane and 0.01 g of γ-butyrolactone to prepare a hydrophilic coating solution and a primer solution.

[0050] 1.5 g of PVP with a brand number of K90 and 3 g of PVP with a brand number of K120 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%.

[0051] Take the intraocular lens introduction head, drip the hydrophilic coating primer solution into the inner cavity of the introduction head by primer coating, shake it up and down evenly, cure it in an oven at 120°C for 6 hours, and take it out; drip the hydrophilic coating top coating solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120°C for 6 hours, and take it out; obtain the hydrophilic coating intraocular lens introduction head. (This embodiment is mainly to increase the solution concentration and increase the curing time) Take a +20.0 degree intraocular lens, fold it with lens forceps and put it into the introduction head, and connect the introduction head to the pusher. After the intraocular lens is placed in the introduction head for 3 minutes, push the lens. The results of the lens push are shown in Table 1.

[0052] Comparative Example 1: 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, and prepare a hydrophilic coating solution and a primer solution.

[0053] Take 1g of PVP with a brand of K90 and 0.5g of PVP with a brand of K120 and dissolve them in 150g of purified water, and add 0.2g of a trifunctional aziridine compound as a crosslinking agent to prepare a hydrophilic coating surface coating solution with a mass fraction of 1%. (This comparative example is mainly without adding maleic anhydride copolymer).

[0054] Take the intraocular lens introduction head, drip the hydrophilic coating primer solution into the inner cavity of the introduction head by primer coating, 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 top coating 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.

[0055] Take a +20.0 degree intraocular lens, fold it with lens forceps and put it into the introduction head, and connect the introduction head to the pusher. After the intraocular lens is placed in the introduction head for 3 minutes, push the lens. The results of the lens push are shown in Table 1.

[0056] Comparative Example 2: Take 1 g of PSMA in a 250 mL flask, add excess sodium hydroxide, react at room temperature for 1 h, and after the polymer is completely hydrolyzed and the aqueous solution is clear and transparent, add dilute hydrochloric acid to adjust the pH to 5, so that a part of the carboxylic acid is retained in the system, and prepare an aqueous solution with a mass fraction of 1%. Add hydroxymethyl cellulose to the system, and its mass fraction in the aqueous solution is 0.1%. Then add 0.1 g of commercially available hydrophilic polyurethane and 0.01 g of γ-butyrolactone to prepare a hydrophilic coating solution and a primer solution.

[0057] Take 3.0g of PVP with the brand name K120 and dissolve it in 150g of purified water, and add 0.2g of trifunctional aziridine compound as a crosslinking agent to prepare a hydrophilic coating surface coating solution with a mass fraction of 2%. (This comparative example mainly uses a PVP with a K value) Take the intraocular lens introduction head, drip the hydrophilic coating primer solution into the inner cavity of the introduction head by primer coating, 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 top coating solution into the inner cavity of the introduction head again, 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] Take a +20.0 degree intraocular lens, fold it with lens forceps and put it into the introduction head, and connect the introduction head to the pusher. After the intraocular lens is placed in the introduction head for 3 minutes, push the lens. The results of the lens push are shown in Table 1.

[0059] Comparative Example 3: Take 1 g of PSMA in a 250 mL flask, add excess sodium hydroxide, react at room temperature for 1 h, and after the polymer is completely hydrolyzed and the aqueous solution is clear and transparent, add dilute hydrochloric acid to adjust the pH to 5, so that a part of the carboxylic acid is retained in the system, and prepare aqueous solutions with a mass fraction of 5%, add hydroxymethyl cellulose to the system, and its mass fraction in the aqueous solution is 0.1%. Then add 0.1 g of commercially available hydrophilic polyurethane to prepare a hydrophilic coating solution and primer solution.

[0060] 1.5 g of PVP with a brand number of K90 and 3 g of PVP with a brand number of K120 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 introduction head, drip the hydrophilic coating primer solution into the inner cavity of the introduction head by primer coating, shake it up and down evenly, cure it in an oven at 120℃ for 1h, and take it out; drip the hydrophilic coating top coating solution into the inner cavity of the introduction head, shake it up and down evenly, cure it in an oven at 120℃ for 1h, and take it out; get the hydrophilic coating intraocular lens introduction head. (This comparative example does not add γ-butyrolactone, and reduces the curing time) Take a +20.0 degree intraocular lens, fold it with lens forceps and put it into the introduction head, and connect the introduction head to the pusher. After the intraocular lens is placed in the introduction head for 3 minutes, push the lens. The results of the lens push are shown in Table 1.

[0062] Table 1 Results of intraocular lens injection

[0063] 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, and the bonding force between the primer and the substrate is enhanced by adding a water-based polyurethane and a maleic anhydride copolymer derivative curing system to the primer solution; hydrogen bonding between water-based polyurethane and polyvinyl pyrrolidone molecules, a cross-linking reaction between maleic anhydride copolymer derivatives and trifunctional aziridine compounds, etc., are constructed, and an interpenetrating chemical cross-linking structure is constructed between the hydrophilic coating primer and the top coating, thereby enhancing the bonding force between the primer and the top coating.

[0064] 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.

[0065] By comparing Comparative Example 3 with Example 3, it is shown that the hydrophilic coating solution of the present invention adopts a fully thermal curing method, and γ-butyrolactone is added to the primer solution to make 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 there will be no jamming problem even if the crystal stays in the introduction head for a period of time and then starts.

[0066] The invention concept is described in detail using specific examples herein, and the description of the above embodiments is only used to help understand the core idea of ​​the invention. It should be pointed out that any obvious modification, equivalent substitution or other improvement made by a person of ordinary skill in the art without departing from the invention concept should be included in the protection scope 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 surface coating solution. The mass ratio of each component in the primer solution is: 0.1-5% of maleic anhydride copolymer derivative, 0.01-0.5 of waterborne polyurethane and maleic anhydride copolymer derivative, 0.01-0.05% of gamma-butyrolactone, 0.05-1% of curing agent, and 95-97% of purified water. The mass ratio of each component in the surface coating solution is: 0.1-5% of hydrophilic polymer, 0.05-1% of crosslinking agent, and 95-97% of purified water.

2. A 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. A 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. A hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 3, characterized in that: The hydrophilic polymer is a mixture of polyvinyl pyrrolidone with different molecular weights, a mixture of polyethylene glycol, a mixture of polyacrylamide, a mixture of polyvinyl alcohol, or a mixture of natural polysaccharides and derivatives.

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

6. 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 5, 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 fully 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, crosslinking agent, and purified water solution are fully stirred and dissolved.

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 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.

8. The method for preparing a hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 7, characterized in that: In S1, the step of aminolysis of the maleic anhydride copolymer derivative is: taking the maleic anhydride copolymer derivative into 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 to fully stir the reaction, 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.

9. 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 5, characterized in that: The steps include: S1: before the hydrophilic coating treatment, the inner cavity surface of the medical catheter is activated, and 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 and cure at 80-120° C. for 1-6 hours; S3: applying the top coating 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.

10. The method for using a hydrophilic coating solution for the inner cavity surface of a medical catheter according to claim 9, 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.

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