CN110916850A - Artificial lens with rear surface being modified in partition mode and preparation method thereof - Google Patents
Artificial lens with rear surface being modified in partition mode and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses or corneal implants; Artificial eyes
- A61F2/16—Intraocular lenses
- A61F2/1613—Intraocular lenses having special lens configurations, e.g. multipart lenses; having particular optical properties, e.g. pseudo-accommodative lenses, lenses having aberration corrections, diffractive lenses, lenses for variably absorbing electromagnetic radiation, lenses having variable focus
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Abstract
本发明公开了一种后表面分区修饰的人工晶状体及其制备方法，所述人工晶状体包括光学部和襻，所述光学部后表面的中央区域为TGF‑β2抗体多层纳米膜，其余周边区域为高粘性界面，所述TGF‑β2抗体多层纳米膜的厚度为6.35～7.85nm，所述人工晶状体被植入眼内大于2周时，所述人工晶状体通过所述高粘性界面能够与晶状体囊膜紧密贴附。通过在人工晶状体后表面构建周边区高粘性界面和中央区TGF‑β2抗体多层纳米膜，以实现对人工晶状体的后表面分区修饰，通过双重机制抑制晶状体上皮细胞的迁移和转分化，从而显著降低后发性白内障的发生率。
The invention discloses an intraocular lens with modified posterior surface partitions and a preparation method thereof. The intraocular lens includes an optical part and a haptic. The central area of the posterior surface of the optical part is a TGF-β2 antibody multilayer nano-film, and the remaining peripheral areas are It is a highly viscous interface, the thickness of the TGF-β2 antibody multilayer nanofilm is 6.35-7.85 nm, and when the intraocular lens is implanted in the eye for more than 2 weeks, the intraocular lens can be connected to the lens through the high viscosity interface. The capsule is tightly attached. By constructing a high-viscosity interface in the peripheral area and a multi-layer nanofilm of TGF-β2 antibody in the central area on the posterior surface of the intraocular lens to realize the modification of the posterior surface of the intraocular lens, the migration and transdifferentiation of lens epithelial cells are inhibited through dual mechanisms, thereby significantly Reduce the incidence of cataract after cataract.
Description
Technical Field
The invention belongs to the field of medical implant materials, and particularly relates to an intraocular lens with a modified rear surface in a partition manner and a preparation method thereof.
Background
Cataract is the most common reversible blindness-causing eye disease in clinic at present, and the patients can quickly recover vision by adopting ultrasonic emulsification and artificial lens implantation operation. However, approximately 30% -50% of patients develop posterior lens capsule opacification (i.e., posterior cataract) within 2-5 years of surgery, resulting in a further loss of vision. Proliferation, migration and transdifferentiation of residual lens cells after cataract surgery are the main causes of posterior capsular opacification.
At present, the surface modification of the artificial lens is adopted to increase the biocompatibility of the artificial lens or the artificial lens is used as a drug slow-release carrier, and the artificial lens becomes a main means for inhibiting the after cataract. For example, patent application publication No. CN 103405807A discloses an artificial lens with comb-shaped polymer on its surface modified by hydrophilicity and its preparation method, which obtains hydrophilic surface by surface modification of artificial lens to inhibit adhesion of lens epithelial cells, thereby reducing occurrence of after cataract.
Further, as disclosed in patent application publication No. CN101053680A, an intraocular lens having an antiproliferative drug coating for preventing the formation of posterior capsule is disclosed, in which antiproliferative drugs or bioactive macromolecules are loaded on the surface of the intraocular lens to inhibit the proliferation, migration or transdifferentiation of lens epithelial cells.
Although the two patent applications have partial effect on the inhibition of the after cataract, the after cataract can be only partially inhibited because the after cataract is only acted on one link of the pathophysiological process of the body spontaneous repair reaction after cataract operation, such as proliferation, migration or transdifferentiation of lens epithelial cells and the like.
Disclosure of Invention
In view of the above, the invention provides an intraocular lens with a modified posterior surface region and a preparation method thereof, wherein a peripheral region high-viscosity interface and a central region TGF- β 2 antibody multilayer nano-membrane are constructed on the posterior surface of the intraocular lens to realize the modification of the posterior surface region of the intraocular lens, and migration and transdifferentiation of lens epithelial cells are inhibited through a dual mechanism, so that the incidence rate of posterior cataract is remarkably reduced.
The technical scheme of the invention is as follows:
the intraocular lens with the modified posterior surface comprises an optical part and a haptic, wherein the central area of the posterior surface of the optical part is a TGF- β 2 antibody multilayer nano-membrane, the rest peripheral areas are high-viscosity interfaces, the thickness of the TGF- β 2 antibody multilayer nano-membrane is 6.35-7.85 nm, and when the intraocular lens is implanted into an eye for more than 2 weeks, the intraocular lens can be tightly attached to a lens capsule membrane through the high-viscosity interfaces.
In the present invention, the classification criteria of the degree of surface tackiness of the intraocular lens include mechanical physical criteria and clinical functional criteria. Mechanical physical standards: the intraocular lens is flatly placed on a clean glass surface, then the edge of the intraocular lens is clamped by an ophthalmic forceps and is completely lifted from the glass surface, and the viscosity of the intraocular lens is divided into three levels according to the force required by the operation, wherein the three levels are respectively as follows: mild: the artificial lens can be easily lifted from the glass surface by using forceps; medium: the artificial lens is labor-consuming, but can be lifted from the glass surface by forceps; and (3) severe degree: the artificial lens cannot be lifted from the glass surface by tweezers, and the artificial lens is easy to break when the artificial lens is forcibly lifted. The high-viscosity interface is moderate and severe in viscosity.
Clinical functional criteria: the surface tackiness of an intraocular lens implanted in a lens capsule is classified into two levels of low tackiness and high tackiness depending on the degree of adhesion between the intraocular lens and the lens capsule at 2 weeks after cataract surgery. Low viscosity: under a slit lamp microscope, the condition that the intraocular lens and the lens capsule membrane are not obviously attached and an obvious gap is formed between the intraocular lens and the lens capsule membrane can be observed. High viscosity: the close adhesion of the intraocular lens and the lens capsule can be observed under a slit lamp microscope, and no gap is left between the intraocular lens and the lens capsule. The viscosity of the high-viscosity interface is high viscosity.
The high-viscosity interface in the peripheral area has strong viscosity and chemical activity, can be tightly adhered and combined with the anterior capsule and the posterior capsule near the capsulorhexis in the eyes, further enhances the mechanical barrier effect of 'capsular bag bending', and further reduces the number of lens epithelial cells which are migrated to the center of the posterior capsule by passing through the edge of the artificial lens;
the TGF- β antibody multilayer nano-membrane in the central area can be adjacent to and even in contact with lens epithelial cells which are flung over the edge of the intraocular lens and migrate to the center of the posterior capsule, the TGF- β antibody deposited on the posterior surface of the intraocular lens can capture TGF- β 2 in a microenvironment near the posterior capsule, and the transdifferentiation of the lens epithelial cells induced by TGF- β 2 is obviously inhibited, so that the generation of posterior capsule opacification is further inhibited.
The ratio of the TGF- β 2 antibody multilayer nano-membrane in the central area to the high-viscosity interface in the peripheral area directly influences the effect of inhibiting the migration and transdifferentiation of lens epithelial cells in the center of the posterior capsule membrane, and experiments prove that when the central area occupies the diameter 1/2-2/3 of the optical part, the inhibition effect of the TGF- β 2 antibody multilayer nano-membrane on the transdifferentiation of the lens epithelial cells induced by TGF- β 2 and the blocking effect of the high-viscosity interface on the migration data of the intraocular lens edge cells are optimal, and the incidence rate of the posterior cataract can be obviously reduced.
Preferably, the thickness of the TGF- β 2 antibody multilayer nano-film is 5-10 nm.
A method for preparing an intraocular lens with a modified posterior surface zone, comprising the steps of:
firstly, carrying out plasma pretreatment on the rear surface of an optical part of an artificial lens, rinsing, blow-drying and storing at room temperature;
then, a static layer-by-layer self-assembly technology is adopted to construct a TGF- β 2 antibody multilayer nano-film in the central region of the back surface of the optical region subjected to plasma pretreatment, and the remaining peripheral region is a high-viscosity interface, so that the artificial lens with the modified back surface region is obtained.
Preferably, the plasma pretreatment is one of a dielectric barrier discharge plasma pretreatment under atmospheric pressure and a dielectric barrier discharge plasma pretreatment under sub-atmospheric pressure.
Preferably, when the rear surface of the optical part of the artificial lens is subjected to the pretreatment of the dielectric barrier discharge plasma under the atmospheric pressure, the thickness of the optical part is 0.3-0.5 m3Introducing argon gas at a flow rate of/h for 1min, and inputting electricity at a current frequency of 10kHzDischarging for 40-60 s under the pressure of 30-36V.
Preferably, when the rear surface of the optical part of the artificial lens is subjected to dielectric barrier discharge plasma pretreatment under subatmospheric pressure, the air pressure of a plasma treatment cavity is set to 2000Pa, the atmosphere is adjusted to be in an air mode, and discharging treatment is carried out for 40-60 s at the current frequency of 10kHz, the input voltage of 220V and the power of 70-80W.
Preferably, after the back surface of the optical part of the artificial lens is subjected to plasma pretreatment, the IOL subjected to plasma pretreatment is kept stand in the air for at least 30min, then is rinsed with ultrapure water in a shaking way for 4-6 h, and finally is dried by nitrogen, and is dried and stored at room temperature.
Preferably, the polylysine/TGF- β 2 antibody electrostatic layer-by-layer self-assembly method in a linear growth mode is adopted to construct a TGF- β 2 antibody multilayer nano-film in the central region of the back surface of the optical area subjected to plasma treatment.
Specifically, the specific steps for constructing the TGF- β 2 antibody multilayer nano-film comprise:
(a) placing the artificial lens pretreated by the plasma with the back surface facing upwards, dripping 10-20 mu l of 1-2 mg/mL polyethyleneimine solution into the central area, stably placing at room temperature for 8-12 h, rinsing with ultrapure water for 3 times, 3min each time, and drying with nitrogen;
(b) repeating steps (b-1) and (b-2) alternately at least 3 times;
(b-1) placing the intraocular lens with the posterior surface facing upward, and adding 50-200. mu.g/ml TGF- β dropwise to the central part210-20 mu l of antibody solution, acting for 1h at 4 ℃, rinsing with ultrapure water for 3 times, 3min each time, and drying with nitrogen;
(b-2) placing the rear surface of the intraocular lens upwards, dripping 10-20 mu l of 1-2 mg/ml polylysine solution into the central part, acting at room temperature for 30min, rinsing with ultrapure water for 3 times, 3min each time, and drying with nitrogen;
(c) placing the IOL with the back surface facing upwards, and dripping 50-200 μ g/ml TGF- β into the central part210-20 mul of antibody solution is acted for 1h at 4 ℃, then rinsed 3 times for 3min each time with ultrapure water, and stored in 0.01mol/L phosphate buffer solution at 4 ℃ for later use.
Compared with the prior art, the invention has the beneficial effects that:
the invention obviously inhibits the migration and the transdifferentiation of lens epithelial cells to the center of a posterior capsule membrane by preparing the peripheral region high-viscosity interface and the central region TGF- β 2 antibody multilayer nano-membrane on the rear surface of the artificial lens, thereby obviously reducing the incidence rate of the after-cataract.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
FIG. 1 is a schematic diagram of the optic posterior surface area modification of an intraocular lens;
FIGS. 2A-2F are schematic views showing the process of modifying the posterior surface of the optic portion of the intraocular lens;
FIGS. 3A-3C are schematic diagrams of confocal laser microscope combined immunofluorescence inspection results of a posterior surface zoned intraocular lens;
FIGS. 4A-4H illustrate the effect of zonal modification of the posterior surface of an intraocular lens on the migration of epithelial cells of the lens;
fig. 5A and 5B are schematic diagrams of animal model studies of posterior surface zoned-modified IOLs to prevent posterior cataract.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be further described in detail with reference to the accompanying drawings and examples. It should be understood that the detailed description and specific examples, while indicating the scope of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
In the examples, the TGF- β 2 antibody is one of a monoclonal TGF- β 2 antibody of human or animal origin, and a polyclonal TGF- β 2 antibody of human or animal origin.
The artificial lens is a hard artificial lens or a soft foldable artificial lens, the hard artificial lens is made of polymethyl methacrylate, and the soft foldable artificial lens is made of hydrophobic acrylate or silicone gel.
The prevention and treatment of after cataract in clinic at present is mainly based on the theory of capsular bag bending: the artificial lens designed with the right-angle edge is closely adhered and combined with the front and the rear capsular diaphragms near the capsular bag capsulorhexis opening to cause the rear capsular diaphragm to form a steep right-angle bend at the edge of the artificial lens, and the rear capsular diaphragm can obviously inhibit the proliferated lens cells after cataract operation from crossing the edge of the artificial lens, thereby inhibiting the occurrence of posterior cataract. However, animal experiments and clinical observations show that the partially proliferated lens epithelial cells successfully cross the edge of the orthogonally designed artificial lens to migrate to the center of the posterior capsule, and epithelial-mesenchymal transition differentiation occurs to cause posterior capsular opacification and fibrosis. Accordingly, the present invention provides an intraocular lens with a posterior surface zoned modification to address the above deficiencies.
Example 1
As shown in FIG. 1, the example provides a posterior surface-zoned modified intraocular lens (IOL) comprising an optic and haptics, the central area of the optic's posterior surface being a TGF- β 2 antibody multilayer nanomembrane, the remaining peripheral area being a high viscosity interface.
The high-viscosity interface at the periphery of the IOL is tightly combined with the anterior and posterior capsular membranes to generate mechanical barrier effect and inhibit the HLE from migrating to the surface of the posterior capsular membrane, and TGF- β 2 antibody (dotted arrow) deposited on the posterior surface of the IOL can capture TGF- β 2, thereby further inhibiting the migration and transdifferentiation of the HLE which migrates to the surface of the posterior capsular membrane beyond the periphery of the IOL and finally obviously inhibiting the occurrence of the posterior cataract.
FIGS. 2A-2F are schematic views showing the process of modifying the posterior surface of the optic portion of an intraocular lens, wherein FIG. 2A is an intraocular lens (IOL), FIG. 2B is a plasma-pretreated IOL surface, FIG. 2C is a pretreated IOL with increased viscosity and negative charges (green particles) on the anterior and posterior surfaces, and FIGS. 2D-2F are electrostatic layer-by-layer self-assembly forms for depositing polylysine (red particles) and TGF- β 2 antibody (green particles) layer by layer in the central 4mm region of the IOL posterior surface.
With reference to fig. 2A to 2F, the surface modification of the hydrophobic acrylate IOL by the atmospheric pressure dielectric barrier discharge plasma pretreatment and the linear growth electrostatic layer-by-layer self-assembly technique is taken as an example to illustrate the preparation process of the intraocular lens with the modified posterior surface region as follows:
(1) plasma pretreatment: the dried hydrophobic acrylate IOL was placed at 0.4m in the central region of the surface of the underlying quartz glass plate3Introducing argon at a flow rate of/h for 1min, and discharging at a current frequency of 10kHz and an input voltage of 32V for 40 s; standing the IOL pretreated by the plasma in the air for 40min, then rinsing the IOL by ultrapure water in a shaking way for 5h, finally drying the IOL by nitrogen, and drying and storing the IOL at room temperature;
(2) the construction of TGF- β 2 antibody nano multilayer film of the central area of the back surface of the IOL comprises the following sub-steps:
(2-1) placing the back surface of the IOL pretreated by the plasma upwards, dripping 10 mu l of 2mg/mL polyethyleneimine (PEI, polycation) solution into the central area, placing the IOL at room temperature for 10 hours stably, then rinsing the IOL with ultrapure water for 3 times, 3min each time, and drying the IOL with nitrogen;
(2-2) repeating the steps (2-2-1) and (2-2-2) alternately 4 times:
(2-2-1) placing the IOL with the posterior surface facing upward and adding 50. mu.g/ml TGF- β drop-wise to the central portion210 mul of antibody (polyanion) solution is acted for 1h at 4 ℃, and then rinsed 3 times with ultrapure water, 3min each time, and dried by nitrogen;
(2-2-2) placing the IOL with the back surface facing upward, adding 10 μ l of 1mg/ml polylysine (PLL, polycation) solution dropwise into the central part, allowing to act at room temperature for 30min, rinsing with ultrapure water for 3 times (each time for 3 min), and blowing with nitrogen gas;
(2-3) placing the IOL with the posterior surface facing upward and adding 50. mu.g/ml TGF- β drop-wise to the central portion2The antibody solution 10 μ l was exposed to 4 ℃ for 1h, and then rinsed 3 times with ultrapure water for 3min each, to construct PEI- (TGF- β) in the central portion of the posterior surface of the IOL2antibody/PLL)4-TGF-β2The antibody nano multilayer film has the thickness of 7.85 and is stored in 0.01mol/LPBS solution at 4 ℃ for later use.
Confocal laser microscope combined immunofluorescence examination is carried out on the artificial lens with the modified rear surface, and the result schematic diagram is shown in fig. 3A-3C, wherein the direct immunofluorescence examination in fig. 3A shows that no TGF- β 2 antibody is deposited in the area of 1mm of the periphery of the rear surface of the IOL, and a little TGF- β 2 antibody is deposited in the area close to the center (green fluorescence), the direct immunofluorescence examination in fig. 3B shows that dense and uniform TGF- β 2 antibody is deposited in the area of 4mm of the central area of the rear surface of the IOL (green fluorescence), and the indirect immunofluorescence examination in fig. 3C shows that the dense and uniformly distributed immunofluorescence deposition particles in the central area of the rear surface of the IOL, so that TGF- β 2 antibody in the self-assembled film keeps good immunocompetence and can capture exogenous TGF- β 2.
Scratch test detection is carried out on the prepared artificial lens with the modified rear surface area so as to illustrate the influence of the artificial lens with the modified rear surface area on the migration of human lens epithelial cells, and the detection results are shown in fig. 4A to 4H. At 0h post-scratch, the scratched areas on the surfaces of the central (FIG. 4A) and peripheral (FIG. 4B) portions of the IOL were sharp and similar in area. At 12h post-scratching, only a few cell protrusions were formed at the edge of the scratched area on the central portion of the surface, as shown in FIG. 4C, while the number of cell protrusions at the edge of the scratched area on the peripheral portion of the surface was significantly greater than that of the novel IOL surface, and it was seen that a plurality of HLE cells migrated into the scratched area, as shown in FIG. 4D; 24h after scratching, only a few HLE cells migrated into the scratched area on the central portion surface, as shown in FIG. 4E, while more HLE cells migrated into the scratched area on the peripheral portion surface, as shown in FIG. 4F; at 48H after scratching, only a few HLE cells migrated into the scratched area on the central portion surface, as shown in FIG. 4G, while HLE cells migrated into the scratched area on the peripheral portion surface had spread over the scratch area, as shown in FIG. 4H. It can be seen that the scratch test shows that the posterior surface-zoned modified IOL has significantly reduced migration of the central LECs, while the peripheral LECs have greater migration.
The artificial lens with the modified rear surface area is also applied to a rabbit eye after-cataract model for simulation, the simulation result is shown in fig. 5A and 5B, and fig. 5A shows that the rabbit eye after-capsule membrane of an experimental group only has slight fibrosis and fine wrinkles; fig. 5B shows the control rabbit eye with significant capsular fibrosis and shrinkage. It can be shown that posterior surface zoned-modified IOLs can significantly reduce the incidence of posterior cataracts compared to untreated IOLs, i.e., posterior surface zoned-modified IOLs can significantly inhibit the occurrence of posterior cataracts.
Example 2
Taking the surface modification of hydrophobic acrylate IOL by the dielectric barrier discharge plasma pretreatment and the linearly-increased electrostatic layer-by-layer self-assembly technology under the sub-atmospheric pressure as an example, the preparation process of the artificial lens with the modified rear surface partition is as follows:
(1) plasma pretreatment: placing the dried hydrophobic acrylate artificial lens in the central area of the surface of a quartz glass plate below, setting the air pressure of a plasma processing cavity to be 2000Pa, adjusting the atmosphere to be an air mode, carrying out electricity discharging processing for 1min under the conditions of current frequency of 10kHz, input voltage of 220V and power of 75W, then carrying out oscillation rinsing for 5h by using ultrapure water, finally carrying out blow-drying by using nitrogen, and carrying out dry preservation at room temperature;
(2) central area TGF- β of IOL posterior surface2The construction of the antibody nano-multilayer film comprises the following steps:
(2-1) placing the artificial lens with the back surface pretreated by the plasma upward, dripping 10 mu l of 2mg/mL Polyethyleneimine (PEI) solution into the central area, stably placing for 10h at room temperature, rinsing with ultrapure water for 3 times, 3min each time, and drying by nitrogen;
(2-2) repeating the steps (2-2-1) and (2-2-2) alternately 4 times:
(2-2-1) the intraocular lens was placed with the posterior surface facing upward, and 50. mu.g/ml TGF- β was dropped into the center210 mu l of antibody solution is acted for 1h at 4 ℃, and then rinsed 3 times with ultrapure water, 3min each time, and dried with nitrogen;
(2-2-2) placing the rear surface of the intraocular lens upward, dripping 10 μ l of Polylysine (PLL) solution of 1mg/ml into the central part, acting at room temperature for 30min, rinsing with ultrapure water for 3 times, 3min each time, and drying with nitrogen;
(2-3) placing the IOL with the posterior surface facing upward and adding 50. mu.g/ml TGF- β drop-wise into the central portion2The antibody solution 10 μ l was exposed to 4 ℃ for 1h, and then rinsed 3 times with ultrapure water for 3min each, to construct PEI- (TGF- β) in the central portion of the posterior surface of the IOL2antibody/PLL)4-TGF-β2The thickness of the antibody nano multilayer film is 7.84nm, and the antibody nano multilayer film is stored in 0.01mol/LPBS solution at 4 ℃ for later use.
The above-mentioned embodiments are intended to illustrate the technical solutions and advantages of the present invention, and it should be understood that the above-mentioned embodiments are only the most preferred embodiments of the present invention, and are not intended to limit the present invention, and any modifications, additions, equivalents, etc. made within the scope of the principles of the present invention should be included in the scope of the present invention.
Claims (9)
1. The intraocular lens with the modified posterior surface is characterized by comprising an optical part and a haptic, wherein the central area of the posterior surface of the optical part is a TGF- β 2 antibody multilayer nano-membrane, the rest peripheral areas are high-viscosity interfaces, the thickness of the TGF- β 2 antibody multilayer nano-membrane is 6.35-7.85 nm, and when the intraocular lens is implanted into an eye for more than 2 weeks, the intraocular lens can be tightly attached to a lens capsule membrane through the high-viscosity interfaces.
2. The posterior surface zoned-modified intraocular lens of claim 1, wherein the central region comprises a diameter of the optic of 1/2-2/3.
3. The posterior surface zoned-modified intraocular lens of claim 1, wherein the TGF- β 2 antibody multilayer nanomembrane has a thickness of 5 to 10 nm.
4. A method for preparing an intraocular lens having a modified posterior surface, the method comprising the steps of:
firstly, carrying out plasma pretreatment on the rear surface of an optical part of an artificial lens, rinsing, blow-drying and storing at room temperature;
then, a static layer-by-layer self-assembly technology is adopted to construct a TGF- β 2 antibody multilayer nano-film in the central region of the back surface of the optical region subjected to plasma pretreatment, and the remaining peripheral region is a high-viscosity interface, so that the artificial lens with the modified back surface region is obtained.
5. The method of making a posterior surface zoned-modified intraocular lens of claim 4, wherein the plasma pretreatment is one of atmospheric pressure dielectric barrier discharge plasma pretreatment and sub-atmospheric pressure dielectric barrier discharge plasma pretreatment.
6. The method for preparing an intraocular lens with a modified posterior surface according to claim 5, wherein the pretreatment of the posterior surface of the optic portion of the intraocular lens with dielectric barrier discharge plasma at atmospheric pressure is performed at a thickness of 0.3 to 0.5m3And introducing argon at the flow rate of/h for 1min, and then discharging for 40-60 s at the current frequency of 10kHz and the input voltage of 30-36V.
7. The method for preparing an intraocular lens with a modified posterior surface according to claim 5, wherein when the posterior surface of the optical portion of the intraocular lens is subjected to dielectric barrier discharge plasma pretreatment under subatmospheric pressure, the pressure of the plasma treatment chamber is set to 2000Pa, the atmosphere is adjusted to an air mode, and the intraocular lens is subjected to discharge treatment for 40 to 60 seconds at a current frequency of 10kHz, an input voltage of 220V, and a power of 70 to 80W.
8. The method of claim 4, wherein the polylysine/TGF- β 2 antibody electrostatic layer-by-layer self-assembly method in linear growth mode is used to construct TGF- β 2 antibody multilayer nanomembrane in the central region of the posterior surface of the optical zone treated by plasma.
9. The method for preparing an intraocular lens with a modified posterior surface according to claim 8, wherein the specific steps of constructing the TGF- β 2 antibody multilayer nanomembrane comprise:
(a) placing the artificial lens pretreated by the plasma with the back surface facing upwards, dripping 10-20 mu l of 1-2 mg/mL polyethyleneimine solution into the central area, stably placing at room temperature for 8-12 h, rinsing with ultrapure water for 3 times, 3min each time, and drying with nitrogen;
(b) repeating steps (b-1) and (b-2) alternately at least 3 times;
(b-1) placing the intraocular lens with the posterior surface facing upward, and adding 50-200. mu.g/ml TGF- β dropwise to the central part210-20 mu l of antibody solution, acting for 1h at 4 ℃, rinsing with ultrapure water for 3 times, 3min each time, and drying with nitrogen;
(b-2) placing the rear surface of the intraocular lens upwards, dripping 10-20 mu l of 1-2 mg/ml polylysine solution into the central part, acting at room temperature for 30min, rinsing with ultrapure water for 3 times, 3min each time, and drying with nitrogen;
(c) placing the IOL with the back surface facing upwards, and dripping 50-200 μ g/ml TGF- β into the central part210-20 mul of antibody solution is acted for 1h at 4 ℃, then rinsed 3 times for 3min each time with ultrapure water, and stored in 0.01mol/L phosphate buffer solution at 4 ℃ for later use.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113018508A (en) * | 2021-03-15 | 2021-06-25 | 西安交通大学医学院第一附属医院 | Surface-modified artificial lens and preparation method thereof |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD234365A1 (en) * | 1985-02-07 | 1986-04-02 | Bezirkskrankenhaus Hoyerswerda | MOUNTING FOR ARTIFICIAL EYE LENS |
| US5002571A (en) * | 1989-02-06 | 1991-03-26 | Donnell Jr Francis E O | Intraocular lens implant and method of locating and adhering within the posterior chamber |
| CN2248543Y (en) * | 1995-08-24 | 1997-03-05 | 张自英 | Artificial lense with adhesion and self-releasing connector |
| CN1582137A (en) * | 2001-10-31 | 2005-02-16 | 博士伦公司 | Intraocular lenses provided with angled edges to prevent posterior capsular opacification |
| CN200973766Y (en) * | 2006-09-20 | 2007-11-14 | 崔浩 | Artificial lentis for preventing disease after cataract operation |
| CN101269240A (en) * | 2008-04-30 | 2008-09-24 | 浙江大学医学院附属第二医院 | Intraocular lens with anti-transforming growth factor β2 antibody film on its surface and its manufacturing method |
| CN104546223A (en) * | 2014-12-16 | 2015-04-29 | 华南理工大学 | Super-hydrophobic posterior chamber intraocular lens with microstructures on surface and preparing method thereof |
| CN106817894A (en) * | 2014-08-07 | 2017-06-09 | 幼鲨科技股份有限公司 | Pattern for flowing control and bioadhesion control |
| CN106901871A (en) * | 2015-12-23 | 2017-06-30 | 爱博诺德（北京）医疗科技有限公司 | Intraocular lens with one or more extentions |
| CN109124826A (en) * | 2017-06-28 | 2019-01-04 | 爱博诺德（北京）医疗科技有限公司 | ophthalmic lens |
-
2019
- 2019-11-21 CN CN201911149246.4A patent/CN110916850A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD234365A1 (en) * | 1985-02-07 | 1986-04-02 | Bezirkskrankenhaus Hoyerswerda | MOUNTING FOR ARTIFICIAL EYE LENS |
| US5002571A (en) * | 1989-02-06 | 1991-03-26 | Donnell Jr Francis E O | Intraocular lens implant and method of locating and adhering within the posterior chamber |
| CN2248543Y (en) * | 1995-08-24 | 1997-03-05 | 张自英 | Artificial lense with adhesion and self-releasing connector |
| CN1582137A (en) * | 2001-10-31 | 2005-02-16 | 博士伦公司 | Intraocular lenses provided with angled edges to prevent posterior capsular opacification |
| CN200973766Y (en) * | 2006-09-20 | 2007-11-14 | 崔浩 | Artificial lentis for preventing disease after cataract operation |
| CN101269240A (en) * | 2008-04-30 | 2008-09-24 | 浙江大学医学院附属第二医院 | Intraocular lens with anti-transforming growth factor β2 antibody film on its surface and its manufacturing method |
| CN106817894A (en) * | 2014-08-07 | 2017-06-09 | 幼鲨科技股份有限公司 | Pattern for flowing control and bioadhesion control |
| CN104546223A (en) * | 2014-12-16 | 2015-04-29 | 华南理工大学 | Super-hydrophobic posterior chamber intraocular lens with microstructures on surface and preparing method thereof |
| CN106901871A (en) * | 2015-12-23 | 2017-06-30 | 爱博诺德（北京）医疗科技有限公司 | Intraocular lens with one or more extentions |
| CN109124826A (en) * | 2017-06-28 | 2019-01-04 | 爱博诺德（北京）医疗科技有限公司 | ophthalmic lens |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113018508A (en) * | 2021-03-15 | 2021-06-25 | 西安交通大学医学院第一附属医院 | Surface-modified artificial lens and preparation method thereof |
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