CN111790006A - A kind of durable and stable hydrophilic antifouling coating for intraocular lens and preparation method thereof - Google Patents

Abstract

The invention discloses a durable and stable hydrophilic antifouling coating for an intraocular lens and a preparation method thereof. The preparation method includes the following steps: preparing a hydrophilic coating solution with a concentration of 1.5-30 wt%; Surface treatment, the intraocular lens material must be pretreated; the hydrophilic coating solution is applied to the surface of the pretreated intraocular lens material, and then superheated hydrogen cross-linking modification treatment is performed to obtain a durable and stable hydrophilic antifouling coating for intraocular lenses. . The present invention also includes the hydrophilic antifouling coating obtained by the above method. The invention coats a durable and stable hydrophilic antifouling coating on the surface of the intraocular lens, has good hydrophilicity and antifouling properties, and has good anti-protein adsorption, anti-bacterial pollution, anti-cell adhesion and anti-thrombotic properties. It avoids the problem of the adhesion of a large number of proteins, cells and bacteria due to the insufficient anti-fouling properties of the surface of the intraocular lens after implantation.

Description

A kind of durable and stable hydrophilic antifouling coating for intraocular lens and preparation method thereof

technical field

The invention belongs to the technical field of ophthalmic medical implant materials, in particular to a durable and stable hydrophilic antifouling coating for intraocular lenses and a preparation method thereof.

Background technique

Cataract is a common ophthalmic disease that occurs on the lens of the human eye. As long as the lens is cloudy, it can be called cataract. The causes of its pathogenesis include many factors, such as aging, heredity, local nutritional disorders, immune and metabolic abnormalities, trauma, poisoning or radiation, etc. These factors can cause lens metabolic disorders, and then lead to lens protein denaturation and opacity. Cataracts form. Cataracts are one of the most common causes of blindness and visual disability. So far, the world-recognized direct and effective method for the treatment of cataract is surgery, that is, the original cloudy lens is removed and an intraocular lens is implanted by surgery.

Although there are various types of intraocular lens products, after the intraocular lens is implanted into the human body as a foreign body, on the one hand, the blood-aqueous barrier and the reaction of the uvea after being stimulated by the foreign body are prone to cause inflammation and foreign body reaction. The destruction, stimulation and incomplete removal of epithelial cells make the lens epithelial cells easy to adhere, proliferate, migrate, and apoptotic on the surface of the intraocular lens material after surgery, which in turn causes turbidity of the anterior and posterior surfaces or shrinkage of the capsular bag, resulting in secondary cataracts. Therefore, people have been looking for ways to improve the biocompatibility of intraocular lenses while maintaining good light transmittance during use. Since the IOL mainly interacts with surrounding tissues and body fluids after implantation, its surface properties are the main factor determining the biocompatibility. Therefore, the effective regulation of the surface properties of intraocular lenses by various surface modification methods is the main way to improve its biocapacity. For example, preparing a functional coating on the lens surface by physical or chemical means can effectively improve the biological antifouling properties of the material surface, etc., and can effectively prevent the adhesion of cells, proteins and bacteria on the surface of the intraocular lens, thereby effectively reducing the secondary probability of cataracts. It has been reported that hydrophilic modification of the surface of intraocular lens materials can effectively reduce the adhesion of contaminants such as cells, proteins and bacteria to the lens surface.

However, the hydrophilic surface modification of the existing surface hydrophilic modified intraocular lens involves complex chemical reactions, and the actual operator needs to have a certain chemical synthesis foundation and operation experience. Compared with this, the use of plasma treatment method and chemical vapor deposition method shows sufficient advantages in operation and practice. However, due to the uncontrollable energy of conventional plasma treatment, it is easy to cause surface degradation and damage, and the reaction site cannot be precisely controlled, which limits its application. At the same time, because the chemical vapor deposition method requires the reactant to have a sufficiently high vapor pressure, for the reactant with little volatility at room temperature, it usually needs to be heated to make it volatilize to achieve it. For some active biological functions The reactants of this technique are also limited.

In recent years, a new surface modification technology-Hyperthermal HydrogenInduced Cross-Linking (HHIC) technology has gradually attracted the attention of researchers. Compared with the traditional surface modification technology, HHIC can Reaction at room temperature, no need for other additives, no need to introduce new reactive groups, controllable reaction kinetic energy, selective reaction cross-linking, less side reactions, easy density adjustment, short reaction time and other advantages are called green surface modification technology. The principle is roughly as follows: using hydrogen molecules with appropriate energy generated by the system (hydrogen molecules with energy greater than 10eV are called epithermal hydrogen molecules) to selectively strip hydrogen atoms on C-H, generate carbon radicals and do not destroy other functional groups. A method for realizing molecular chain cross-linking under the premise. Therefore, using HHIC to modify the surface of the material does not cause the fracture and degradation of the C-C bond of the material itself, so that the material can not only maintain the original mechanical properties, transparency and other advantages, but also endow the material surface with other new functions. However, it is mainly aimed at the anti-fogging properties of the surface of engineered materials, which belongs to industrial applications, and has not been studied on the modification of bio-anti-fouling of implanted/interventional biomedical materials and devices. Therefore, through the optimized selection of coatings and the introduction of HHIC technology, it is expected to prepare a special hydrophilic antifouling coating for intraocular lenses with lasting and stable antifouling effect.

SUMMARY OF THE INVENTION

In view of the above deficiencies in the prior art, the present invention provides a durable and stable hydrophilic anti-fouling coating for intraocular lenses and a preparation method thereof. Good hydrophilicity and anti-fouling properties, its anti-protein adsorption, anti-bacterial pollution, anti-cell adhesion and anti-thrombotic properties are good, which avoids the lack of surface anti-fouling properties of intraocular lenses after implantation. The problem of bacterial adhesion.

In order to achieve the above object, the technical solution adopted by the present invention to solve the technical problem is: a preparation method of a durable and stable hydrophilic antifouling coating for intraocular lenses is provided, comprising the following steps:

(1) adding the hydrophilic polymer into the solvent to prepare a hydrophilic coating solution with a concentration of 1.5-30 wt%;

(2) low-temperature plasma surface treatment is performed on the surface of the intraocular lens material to obtain pretreated intraocular lens material;

(3) applying the hydrophilic coating solution obtained in step (1) to the surface of the pretreated intraocular lens material obtained in step (2), and then carrying out superheat hydrogen cross-linking modification treatment to obtain a lasting and stable hydrophilic resistance for intraocular lens. dirty coating.

Further, the hydrophilic polymer is polyethylene glycol, polyoxyethylene, poly-2-methacryloyloxyethyl phosphorylcholine, polyvinylpyrrolidone, polyacrylic acid, polyvinyl alcohol, hyaluronic acid, collagen, heparin and at least one of hirudin.

Further, the weight average molecular weight of polyethylene glycol Mw≤2×10 ⁴ g/mol, and the weight average molecular weight of polyoxyethylene Mw≥2×10 ⁴ g/mol.

Further, the solvent is at least one of water, methanol, ethanol, acetone, chloroform and dichloromethane.

Further, the intraocular lens material is rigid polymethyl methacrylate, soft silicone rubber, silicone gel, polyhydroxyethyl methacrylate or hydrophobic acrylate.

Further, in step (2), the voltage during the low temperature plasma surface treatment is 50-200V, and the time is 1-120s.

Further, in step (3), the coating method is dip coating, spin coating, drop coating or spray coating.

Further, in step (3), during the superthermal hydrogen crosslinking modification treatment, the voltage is 50-300V, the vacuum degree is 0.001-0.2Pa, and the time is 5-180s.

A durable and stable hydrophilic antifouling coating for an intraocular lens prepared by the above-mentioned preparation method of a durable and stable hydrophilic antifouling coating for an intraocular lens.

Further, the contact angle of the surface of the durable and stable hydrophilic antifouling coating for the intraocular lens is 0-80°.

To sum up, the present invention has the following advantages:

1. The present invention coats the surface of the intraocular lens with a durable and stable hydrophilic antifouling coating, which has good hydrophilicity and antifouling properties, and its anti-protein adsorption, anti-bacterial pollution, anti-cell adhesion and anti-thrombotic properties. Good, has good biocompatibility, avoids the problem of adhesion of a large number of proteins, cells and bacteria due to insufficient surface anti-fouling performance after intraocular lens implantation, and reduces the biocompatibility of the surface of intraocular lens materials after cataract surgery. A series of complications caused by sexual insufficiency.

2. The preparation process of the durable and stable hydrophilic antifouling coating for intraocular lenses is simple, suitable for various intraocular lens materials, and can be modified in batches, with low cost, and the modified materials can be used in disinfection, packaging and transportation. It is also very convenient and has the potential for industrial operation and production. A hydrophilic coating solution is prepared by using a hydrophilic polymer, which is used to form a hydrophilic coating on the surface of an intraocular lens to improve the hydrophilicity and antifouling properties of the material, so that it has better biocompatibility; The surface of the material is treated with low-temperature plasma, which is simple and easy to control, and can achieve precise and controllable reaction sites. Advantages, it can also avoid the toxic side effects of drug-coated intraocular lenses on non-targeted cells in the application.

3. The coating solution can be prepared from various polymers with good hydrophilicity. It is not limited by the type of polymer. It can be freely selected and flexibly combined according to the expected function, and is not limited by the coating method. The durable and stable hydrophilic antifouling coating for intraocular lenses has good adhesion on the intraocular lens, making it not easy to fall off in the intraocular environment, and the physical and chemical properties of the intraocular lens itself are not affected, and can play its biological role lastingly and stably. Anti-fouling effect.

Description of drawings

Fig. 1 is the surface contact angle of polymethyl methacrylate intraocular lens material before and after pretreatment;

Figure 2 shows the surface contact angles of different coating concentrations treated with the same superthermal hydrogen crosslinking modification conditions;

Figure 3 is a fluorescent picture of culturing with mouse fibroblasts (L929) for 1 day before and after superthermal hydrogen cross-linking modification treatment;

FIG. 4 is a schematic diagram of the experimental results of protein adsorption before and after the superthermal hydrogen crosslinking modification treatment.

Detailed ways

Example 1

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) Configure a polyoxyethylene solution with a concentration of 10 mg/ml;

(2) subjecting the surface of the rigid polymethyl methacrylate intraocular lens material to a low-temperature plasma surface treatment at a voltage of 70V for 60s to obtain a pretreated rigid polymethyl methacrylate intraocular lens material;

(3) put the pretreated rigid polymethyl methacrylate intraocular lens material obtained in step (2) into the polyoxyethylene solution obtained in step (1), immerse it for 30 minutes, take out, blow dry with nitrogen, and then under the conditions of 150V and 0.01Pa vacuum degree The ultra-thermal hydrogen cross-linking modification treatment was carried out for 35 s to obtain a durable and stable hydrophilic and antifouling coating for intraocular lenses.

Example 2

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) Configure a polyvinylpyrrolidone solution with a concentration of 6 mg/ml;

(2) subjecting the surface of the rigid polymethyl methacrylate intraocular lens material to a low-temperature plasma surface treatment at a voltage of 150V for 20s to obtain a pretreated rigid polymethyl methacrylate intraocular lens material;

(3) Put the pretreated rigid polymethyl methacrylate intraocular lens material obtained in step (2) into the polyvinylpyrrolidone solution obtained in step (1), immerse it for 30 minutes, take out, blow dry with nitrogen, and then vacuum at 200V and 0.01Pa. Under the condition of superthermal hydrogen crosslinking modification treatment for 180s, a durable and stable hydrophilic antifouling coating for intraocular lens was obtained.

Example 3

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) Configure a polyoxyethylene solution with a concentration of 8 mg/ml;

(2) subjecting the surface of the polyhydroxyethyl methacrylate intraocular lens material to a low-temperature plasma surface treatment at a voltage of 120V for 120s to obtain a pretreated polyhydroxyethyl methacrylate intraocular lens material;

(3) Put the pretreated polyhydroxyethyl methacrylate intraocular lens material obtained in step (2) into the polyoxyethylene solution obtained in step (1), immerse it for 30 minutes, take out, blow dry with nitrogen, and then under the conditions of 100V and 0.2Pa vacuum degree The ultra-thermal hydrogen cross-linking modification treatment was carried out for 120 s to obtain a durable and stable hydrophilic and antifouling coating for intraocular lenses.

Example 4

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) Configure a polyoxyethylene solution with a concentration of 4 mg/ml;

(2) subjecting the surface of the polyhydroxyethyl methacrylate intraocular lens material to a low-temperature plasma surface treatment at a voltage of 150V for 90s to obtain a pretreated polyhydroxyethyl methacrylate intraocular lens material;

(3) Put the pretreated polyhydroxyethyl methacrylate intraocular lens material obtained in step (2) into the polyoxyethylene solution obtained in step (1), immerse it for 60 minutes, take out, blow dry with nitrogen, and then under the conditions of 150V and 0.056Pa vacuum degree The ultra-thermal hydrogen cross-linking modification treatment was carried out for 90 s to obtain a durable and stable hydrophilic and antifouling coating for intraocular lenses.

Example 5

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) configure the poly-2-methacryloyloxyethyl phosphorylcholine solution with a concentration of 20mg/ml;

(2) The surface of the transparent silicone rubber intraocular lens material is subjected to a low-temperature plasma surface treatment at a voltage of 70V for 45s to obtain a pretreatment of the transparent silicone rubber intraocular lens material;

(3) spin-coating the poly-2-methacryloyloxyethyl phosphorylcholine solution obtained in step (1) on the pretreated transparent silicone rubber intraocular lens material obtained in step (2), and then under the conditions of 100V and 0.099Pa vacuum The ultra-thermal hydrogen cross-linking modification treatment was carried out for 45 s to obtain a durable and stable hydrophilic and antifouling coating for intraocular lenses.

Example 6

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) configure a poly-2-methacryloyloxyethyl phosphorylcholine solution with a concentration of 30mg/ml;

(2) The surface of the transparent silicone rubber intraocular lens material is subjected to a low temperature plasma surface treatment at a voltage of 90V for 20s to obtain a pretreated transparent silicone rubber intraocular lens material;

(3) spin-coating the poly-2-methacryloyloxyethyl phosphoric acid choline solution obtained in step (1) on the pretreated transparent silicone rubber intraocular lens material obtained in step (2), and then under the conditions of 150V and 0.001Pa vacuum The ultra-thermal hydrogen cross-linking modification treatment was carried out for 45 s to obtain a durable and stable hydrophilic and antifouling coating for intraocular lenses.

Example 7

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) configure the poly-2-methacryloyloxyethyl phosphorylcholine solution with a concentration of 10mg/ml;

(2) The surface of the transparent silicone gel intraocular lens material is subjected to low-temperature plasma surface treatment at a voltage of 90V for 90s to obtain a pretreated transparent silicone gel intraocular lens material;

(3) spin-coating the poly-2-methacryloyloxyethylphosphoryl choline solution obtained in step (1) on the pretreated transparent silicone gel intraocular lens material obtained in step (2), and then vacuum at 100V and 0.006Pa. Under the condition of superthermal hydrogen crosslinking modification treatment for 75s, a durable and stable hydrophilic antifouling coating for intraocular lens was obtained.

Example 8

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) configure the poly-2-methacryloyloxyethyl phosphorylcholine solution with a concentration of 10mg/ml;

(2) The surface of the transparent silicone gel intraocular lens material is subjected to a low temperature plasma surface treatment at a voltage of 100V for 60s to obtain a pretreated transparent silicone gel intraocular lens material;

(3) spin-coating the poly-2-methacryloyloxyethylphosphoryl choline solution obtained in step (1) on the pretreated transparent silicone gel intraocular lens material obtained in step (2), and then under vacuum at 150V and 0.005Pa Under the condition of superthermal hydrogen crosslinking modification treatment for 30s, a durable and stable hydrophilic antifouling coating for intraocular lens was obtained.

Example 9

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) Prepare a heparin solution with a concentration of 3 mg/ml;

(2) subjecting the surface of the hydrophobic acrylate intraocular lens material to a low-temperature plasma surface treatment at a voltage of 150V for 15s to obtain a pretreated hydrophobic acrylate intraocular lens material;

(3) Put the pretreated hydrophobic acrylate intraocular lens material obtained in step (2) into the heparin solution obtained in step (1), immerse it for 30 minutes, take out, blow dry with nitrogen, and then carry out superheated hydrogen under the conditions of 150V and 0.001Pa vacuum. After cross-linking modification treatment for 90s, a durable and stable hydrophilic and antifouling coating for intraocular lenses was obtained.

Example 10

A durable and stable hydrophilic antifouling coating for intraocular lenses, the preparation method comprising the following steps:

(1) Configure 2mg/ml hyaluronic acid solution;

(2) subjecting the surface of the hydrophobic acrylate intraocular lens material to a low-temperature plasma surface treatment at a voltage of 100V for 30s to obtain a pretreated hydrophobic acrylate intraocular lens material;

(3) spin-coating the hyaluronic acid solution obtained in step (1) on the pretreated hydrophobic acrylate intraocular lens material obtained in step (2), and then performing superthermal hydrogen crosslinking modification under the conditions of 150V and 0.006Pa vacuum After 60s of treatment, a durable and stable hydrophilic antifouling coating was obtained for the intraocular lens.

The intraocular lenses obtained in the examples were respectively tested for contact angle with a durable and stable hydrophilic antifouling coating (see Figures 1-2), and mouse fibroblasts (L929) were cultured and photographed by fluorescence (see Figure 3). ) and protein adsorption experiments (see Figure 4).

It can be seen from Figures 1 to 4 that, compared with the properties of the untreated intraocular lens material, the lasting and stable hydrophilic antifouling coating for the intraocular lens obtained by the present invention has an obvious increase in the hydrophilicity of the modified biological valve, and has excellent properties. Anti-cell adhesion properties. This is because the hydrophilic coating solution prepared from the hydrophilic polymer is coated on the surface of the intraocular lens to form a hydrophilic coating, which improves the hydrophilicity and antifouling properties of the material and makes it have better biocompatibility.

Although the specific embodiments of the present invention have been described in detail with reference to the accompanying drawings, they should not be construed as limiting the protection scope of this patent. Within the scope described in the claims, various modifications and deformations that can be made by those skilled in the art without creative work still belong to the protection scope of this patent.

Claims (10)

1. a kind of preparation method of lasting stable hydrophilic antifouling coating for intraocular lens, is characterized in that, comprises the following steps: (1) adding the hydrophilic polymer into the solvent to prepare a hydrophilic coating solution with a concentration of 1.5-30 wt%; (2) low-temperature plasma surface treatment is performed on the surface of the intraocular lens material to obtain pretreated intraocular lens material; (3) applying the hydrophilic coating solution obtained in the step (1) to the surface of the pretreated intraocular lens material obtained in the step (2), and then carrying out superthermal hydrogen cross-linking modification treatment to obtain a lasting and stable hydrophilic resistance for intraocular lenses. dirty coating. 2. The preparation method of lasting and stable hydrophilic antifouling coating for intraocular lens as claimed in claim 1, wherein the hydrophilic polymer is polyethylene glycol, polyoxyethylene, poly-2-methyl At least one of acryloyloxyethylphosphorylcholine, polyvinylpyrrolidone, polyacrylic acid, polyvinyl alcohol, hyaluronic acid, collagen, heparin, and hirudin. 3. The method for preparing a durable and stable hydrophilic antifouling coating for intraocular lenses as claimed in claim 2, wherein the polyethylene glycol weight-average molecular weight Mw≤2×10 4 g/mol, the polyethylene glycol weight average molecular weight Mw≤2×10 ⁴ g/mol, the The polyoxyethylene weight-average molecular weight Mw≥2×10 ⁴ g/mol. 4. The preparation method of lasting stable hydrophilic antifouling coating for intraocular lens as claimed in claim 1, wherein the solvent is water, methanol, ethanol, acetone, chloroform and dichloromethane. at least one. 5. The preparation method of the lasting and stable hydrophilic antifouling coating for intraocular lens as claimed in claim 1, wherein the intraocular lens material is rigid polymethyl methacrylate, soft silicone rubber, silicone gel glue, polyhydroxyethyl methacrylate or hydrophobic acrylate. 6. The method for preparing a durable and stable hydrophilic antifouling coating for intraocular lenses as claimed in claim 1, wherein in step (2), the voltage during the low-temperature plasma surface treatment is 50-200V, and the time is 1- 120s. 7 . The method for preparing a durable and stable hydrophilic antifouling coating for intraocular lenses as claimed in claim 1 , wherein in step (3), the coating method is dip coating, spin coating, drop coating or spray coating. 8 . 8 . The method for preparing a durable and stable hydrophilic antifouling coating for intraocular lenses as claimed in claim 1 , wherein in step (3), during the superthermal hydrogen cross-linking modification treatment, the voltage is 50-300V. 9 . , the vacuum degree is 0.001~0.2Pa, and the time is 5~180s. 9 . The durable and stable hydrophilic antifouling coating for intraocular lenses prepared by the method for preparing a durable and stable hydrophilic antifouling coating for intraocular lenses according to any one of claims 1 to 8 . 10 . The durable and stable hydrophilic antifouling coating for an intraocular lens according to claim 9 , wherein the contact angle of the surface of the durable and stable hydrophilic antifouling coating for an intraocular lens is 0° to 80°. 11 .

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