Gold nanoparticle-silicone hydrogel corneal contact lens, preparation method thereof and application of corneal contact lens in intraocular pressure detection

Abstract

The invention belongs to the technical field of intelligent medical equipment, and particularly relates to a gold nanoparticle-silicone hydrogel corneal contact lens, a preparation method thereof and application of the corneal contact lens in intraocular pressure detection. The invention provides a corneal contact lens. The corneal contact lens comprises a middle pupil area and an annular detection area surrounding the middle pupil area. The middle pupil area is a silicone hydrogel elastic film; and the annular detection area is an annular silicone hydrogel elastic film doped with gold nanoparticles. The cornea contact lens provided by the invention is a contact lens capable of monitoring intraocular pressure in real time, is used for intraocular pressure detection, can realize noninvasive, convenient and real-time intraocular pressure monitoring, and is expected to be widely applied to early diagnosis and management of eye diseases such as glaucoma and the like.

Description

Technical Field

[0001] The present invention belongs to the technical field of intelligent medical equipment, and in particular relates to a gold nanoparticle-silicon hydrogel corneal contact lens, a preparation method thereof, and an application thereof in intraocular pressure detection. Background Art

[0002] Intraocular pressure (IOP) is an important indicator for the assessment and management of eye diseases, especially glaucoma. Glaucoma is the world's leading irreversible blinding eye disease and one of the main causes of irreversible vision loss. It is a group of diseases with optic atrophy and visual field defects as common characteristics. It has an insidious onset and pathological increase in intraocular pressure is its main feature. It is also an independent risk factor in the development of glaucomatous optic nerve damage.

[0003] For glaucoma disease management, early screening, early diagnosis, and early treatment are required to preserve effective visual function for patients as much as possible. Therefore, the group that needs intraocular pressure monitoring has become very large. Intraocular pressure is a dynamically changing biological indicator with obvious rhythmicity and fluctuations. Traditional intraocular pressure detection relies on medical equipment such as tonometers. Most of the tonometers currently used in domestic clinical practice are managed as Class II medical devices. Most tonometers are designed based on the Imbert-Fick principle and can be divided into contact and non-contact tonometers. Contact tonometers are relatively rare in clinical practice due to their complex operation and need to be disinfected. Non-contact tonometers have the advantages of effectively avoiding cross-infection, simple use, and fast detection speed, and are more common in clinical practice. However, intraocular pressure is a dynamic physiological parameter, especially in the diagnosis of glaucoma and the recovery period of eye surgery. It is an important basis for treatment. Therefore, the demand for long-term real-time dynamic intraocular pressure monitoring is growing. However, existing medical equipment for intraocular pressure measurement (such as the gold standard Goldmann tonometer) has temporal and spatial limitations and cannot meet the new clinical needs of long-term intraocular pressure monitoring.

[0004] In summary, the tonometers commonly used in China cannot meet the requirements of continuous dynamic monitoring of intraocular pressure. Patients need to go to medical institutions regularly to test their intraocular pressure, which is time-consuming and laborious. At the same time, it is impossible to obtain dynamic intraocular pressure parameters and important information such as pressure curves and pressure peaks over 24 hours or longer. Therefore, the current dynamic monitoring of intraocular pressure is a difficult point in the diagnosis and treatment of glaucoma. Summary of the invention

[0005] The purpose of the present invention is to provide a gold nanoparticle-silicone hydrogel corneal contact lens and a preparation method thereof and an application in intraocular pressure detection. The gold nanoparticle-silicone hydrogel corneal contact lens provided by the present invention is a contact lens that can monitor intraocular pressure in real time. It is used in intraocular pressure detection and can achieve non-invasive, convenient and real-time intraocular pressure monitoring. It is expected to be widely used in the early diagnosis and management of eye diseases such as glaucoma.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] The present invention provides a gold nanoparticle-silicon hydrogel corneal contact lens, comprising a middle pupil area and a ring-shaped detection area surrounding the middle pupil area;

[0008] The middle pupil area is a silicone hydrogel elastic film;

[0009] The annular detection area is an annular silicone hydrogel elastic film doped with gold nanoparticles.

[0010] Preferably, the annular silicone hydrogel elastic film doped with gold nanoparticles comprises an annular silicone hydrogel elastic film and gold nanoparticles doped in the annular silicone hydrogel elastic film, and the particle size of the gold nanoparticles is 30 to 50 nm.

[0011] The present invention provides a method for preparing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution, comprising the following steps:

[0012] (1) placing a silicone hydrogel precursor solution in a mold for preparing an annular silicone hydrogel elastic film for curing, and then demolding to obtain an annular silicone hydrogel elastic film;

[0013] (2) doping the annular silicone hydrogel elastic film to obtain an annular silicone hydrogel elastic film initially doped with gold nanoparticles; the doping comprises etching and impregnation in sequence, the etching is wet etching, and the impregnation is performed using a gold nanoparticle aqueous dispersion;

[0014] (3) placing the annular silicone hydrogel elastic film initially doped with gold nanoparticles and the silicone hydrogel precursor solution in a mold for preparing a corneal contact lens and curing them to obtain the gold nanoparticle-silicone hydrogel corneal contact lens.

[0015] Preferably, the method for preparing the silicone hydrogel precursor solution used in step (1) and step (3) comprises the following steps:

[0016] Hydroxyethyl methacrylate, N-vinyl pyrrolidone, Y-(methacryloyloxy)propyltrimethoxysilane, a crosslinking agent and an initiator are mixed and reacted to obtain a reaction liquid;

[0017] The reaction liquid is separated into solid and liquid to obtain the silicon hydrogel precursor solution.

[0018] Preferably, in step (2): the doping is repeated 5 to 6 times;

[0019] When the doping is performed once, the etching time is 1 to 3 minutes, and the immersion time is 5 to 10 minutes;

[0020] The etching agent used in the wet etching is acetone.

[0021] The present invention provides the use of the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution in intraocular pressure detection.

[0022] The present invention provides a visual intraocular pressure detection method, comprising the following steps:

[0023] Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be tested;

[0024] The color change of the annular detection area of ​​the gold nanoparticle-silicone hydrogel corneal contact lens is observed. When the color of the annular detection area becomes lighter, the intraocular pressure of the eye to be detected increases.

[0025] The present invention provides a method for qualitatively detecting intraocular pressure, comprising the following steps:

[0026] Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be tested;

[0027] An optical fiber spectrometer is used to collect spectral data of the annular detection area of ​​the gold nanoparticle-silicone hydrogel corneal contact lens, and the change in intraocular pressure of the eye is analyzed based on the change in the wavelength of the characteristic absorption peak of the spectral data. When the wavelength of the characteristic absorption peak of the spectral data moves in a gradually decreasing direction, the intraocular pressure of the eye to be detected increases; the characteristic absorption peak of the spectral data is the surface plasma resonance peak of the gold nanoparticles.

[0028] The present invention provides a method for quantitatively detecting intraocular pressure, comprising the following steps:

[0029] Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be tested;

[0030] Using a fiber optic spectrometer to collect spectral data of the annular detection area of ​​the gold nanoparticle-silicone hydrogel contact lens;

[0031] The intraocular pressure to be detected is obtained according to the quantitative relationship between the wavelength of the characteristic absorption peak of the spectral data and the intraocular pressure-characteristic absorption peak wavelength; the characteristic absorption peak of the spectral data is the surface plasma resonance peak of the gold nanoparticles.

[0032] The present invention provides a method for quantitatively detecting intraocular pressure, comprising the following steps:

[0033] Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be tested;

[0034] collecting an optical image of the annular detection area of ​​the gold nanoparticle-silicone hydrogel contact lens;

[0035] The intraocular pressure of the eye to be detected is obtained according to the quantitative relationship between the chromaticity information in the optical image and the chromaticity information of the intraocular pressure-annular detection area.

[0036] The present invention provides a gold nanoparticle-silicone hydrogel corneal contact lens, comprising a middle pupil area and an annular detection area surrounding the middle pupil area; the middle pupil area is a silicone hydrogel elastic film; the annular detection area is an annular silicone hydrogel elastic film doped with gold nanoparticles. The present invention uses a silicone hydrogel elastic film as a carrier film. Since silicone hydrogel has a significant high oxygen permeability, its softness and hydrophilicity make it more comfortable to wear, reduce the foreign body sensation, maintain the moisture of the eyes, reduce dry eye symptoms, and enhance the compliance of wearing corneal contact lenses; the present invention uses an annular silicone hydrogel elastic film area doped with gold nanoparticles as an annular detection area to ensure that the middle pupil position is still made of silicone hydrogel material, and the annular detection area beyond the pupil position is made of an annular silicone hydrogel material containing gold nanoparticles, and the color of the annular detection area is colored according to the size of the nanoparticles (the gold nanoparticles with a particle size of 30 to 50 nm used in the embodiment of the present invention are red). When the measured value of intraocular pressure is normal, the outer annular detection area of ​​the contact lens worn by the corresponding person will appear red; once the intraocular pressure increases and the eyeball expands, the distance between the gold nanoparticles contained in the annular detection area will change, and the color of the annular detection area will become lighter. The color change of the annular detection area can be used to visualize the change of intraocular pressure. When it is dark or the surrounding environment is not conducive to directly observing the color change of the annular detection area, further qualitative or quantitative detection can be performed through detection equipment such as fiber optic spectrometers.

[0037] In summary, the gold nanoparticle-silicone hydrogel corneal contact lens provided by the present invention utilizes gold nanoparticles doped with silicon hydrogel to prepare a corneal contact lens with a colored annular detection area, and the obtained corneal contact lens product is used for intraocular pressure monitoring. The present invention combines the optical properties of gold nanoparticles with the biocompatibility of silicon hydrogel, and the obtained gold nanoparticle-silicone hydrogel corneal contact lens for intraocular pressure detection has good transparency and comfort, and the uniform distribution of gold nanoparticles in the silicon hydrogel in the annular detection area ensures the accuracy and stability of the measurement. The gold nanoparticle-silicone hydrogel corneal contact lens provided by the present invention can monitor the changes in intraocular pressure in real time by detecting the optical changes of gold nanoparticles, realizing non-invasive, convenient, and real-time intraocular pressure monitoring, and is expected to be widely used in the early diagnosis and management of eye diseases such as glaucoma.

[0038] The preparation method of the gold nanoparticle-silicone hydrogel corneal contact lens provided by the present invention is simple and efficient. The prepared gold nanoparticle-silicone hydrogel corneal contact lens uses silicone hydrogel material, has excellent biocompatibility, and can be worn for a long time; at the same time, the unique optical and electrical properties of gold nanoparticles are utilized to enable it to detect tiny pressure changes, thereby providing accurate intraocular pressure measurement results, and has high sensitivity and accuracy. Therefore, the gold nanoparticle-silicone hydrogel corneal contact lens provided by the present invention has good biocompatibility and long-term stability when used to detect intraocular pressure of the eyeball. At the same time, it is non-invasive and portable, can reduce mechanical damage to the eyeball, and does not affect the wearer's vision and comfort, and can effectively meet clinical needs.

[0039] The present invention provides a method for visualizing intraocular pressure detection, comprising the following steps: wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be detected; observing the color change of the annular detection area of ​​the gold nanoparticle-silicone hydrogel corneal contact lens, when the color of the annular detection area becomes lighter, the intraocular pressure of the eyeball to be detected increases. The method for visualizing intraocular pressure detection provided by the present invention realizes preliminary intraocular pressure detection by directly observing the color change of the annular detection area of ​​the gold nanoparticle-silicone hydrogel corneal contact lens after wearing. When the intraocular pressure is elevated, the distance between the gold nanoparticles in the annular detection area increases, and the color of the annular detection area becomes lighter. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 A schematic diagram of the structure of a corneal contact lens provided by the present invention;

[0041] Figure 1 Middle: 1 is the middle pupil area, 2 is the ring detection area;

[0042] Figure 2A schematic structural diagram of an upper mold and a lower mold of a mold for preparing a corneal contact lens provided in an embodiment of the present invention;

[0043] Figure 2 Middle: 3 is a lower mold for preparing a corneal contact lens, and 4 is an upper mold for preparing a corneal contact lens;

[0044] Figure 3 A schematic structural diagram of an upper mold and a lower mold of a mold for preparing an annular silicone hydrogel elastic film provided in an embodiment of the present invention;

[0045] Figure 3 Middle: 3 is a lower mold of a mold for preparing an annular silicone hydrogel elastic film, and 5 is an upper mold of a mold for preparing an annular silicone hydrogel elastic film;

[0046] Figure 4 It is a schematic diagram of the spectrum detection process of the present invention;

[0047] Figure 5 It is a spectrum comparison diagram of the silicone hydrogel corneal lens (blank film) and the AuNPs-silicone hydrogel corneal lens in the present invention;

[0048] Figure 6 The spectrum comparison of the gold nano-silicon hydrogel film under the condition of simulated elevated intraocular pressure of the present invention;

[0049] Figure 7 Actual pictures of the silicone hydrogel corneal lens (blank film) and AuNPs-silicone hydrogel corneal lens prepared in the embodiments of the present invention. DETAILED DESCRIPTION

[0050] The present invention provides a gold nanoparticle-silicon hydrogel corneal contact lens, comprising a middle pupil area and a ring-shaped detection area surrounding the middle pupil area;

[0051] The middle pupil area is a silicone hydrogel elastic film;

[0052] The annular detection area is an annular silicone hydrogel elastic film doped with gold nanoparticles.

[0053] In the present invention, unless otherwise specified, all preparation raw materials / components are commercially available products well known to those skilled in the art.

[0054] The structural schematic diagram of the gold nanoparticle-silicon hydrogel corneal contact lens provided by the present invention is as follows Figure 1 As shown, the following combination Figure 1 The gold nanoparticle-silicone hydrogel corneal contact lens provided by the present invention is described in detail.

[0055] The gold nanoparticle-silicon hydrogel corneal contact lens provided by the present invention comprises a middle pupil area and an annular detection area surrounding the middle pupil area. The middle pupil area and the annular detection area surrounding the middle pupil area are integrally formed.

[0056] In the present invention, the middle pupil region is a silicone hydrogel elastic film. In the present invention, the thickness of the middle pupil region is ≤0.3 mm, preferably 0.04 to 0.09 mm.

[0057] In the present invention, the annular detection area is an annular silicone hydrogel elastic film doped with gold nanoparticles. In the present invention, the annular silicone hydrogel elastic film doped with gold nanoparticles comprises an annular silicone hydrogel elastic film and gold nanoparticles doped in the annular silicone hydrogel elastic film. The particle size of the gold nanoparticles in the annular silicone hydrogel elastic film doped with gold nanoparticles is preferably 30 to 50 nm. The thickness of the annular detection area is ≤0.15 mm, preferably 0.04 to 0.06 mm.

[0058] The present invention provides a method for preparing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution, comprising the following steps:

[0059] (1) placing a silicone hydrogel precursor solution in a mold for preparing an annular silicone hydrogel elastic film for curing, and then demolding to obtain an annular silicone hydrogel elastic film;

[0060] (2) doping the annular silicone hydrogel elastic film to obtain an annular silicone hydrogel elastic film initially doped with gold nanoparticles; the doping comprises etching and impregnation in sequence, the etching is wet etching, and the impregnation is performed using a gold nanoparticle aqueous dispersion;

[0061] (3) placing the annular silicone hydrogel elastic film initially doped with gold nanoparticles and the silicone hydrogel precursor solution in a mold for preparing a corneal contact lens and curing them to obtain the gold nanoparticle-silicone hydrogel corneal contact lens.

[0062] The present invention places a silicone hydrogel precursor solution (hereinafter referred to as the first silicone hydrogel precursor solution) in a preparation mold for an annular silicone hydrogel elastic film for curing (hereinafter referred to as the first curing), and obtains an annular silicone hydrogel elastic film after demoulding. In the present invention, the preparation method of the first silicone hydrogel precursor solution preferably includes the following steps: mixing hydroxyethyl methacrylate (HEMA), N-vinyl pyrrolidone (NVP), Y-(methacryloyloxy)propyltrimethoxysilane (KH-570), a crosslinker and an initiator to react to obtain a reaction liquid; separating the reaction liquid from the solid-liquid to obtain the silicone hydrogel precursor solution. The volume ratio of HEMA, NVP and KH-570 is preferably 8.5:1:0.5. The crosslinker is specifically preferably N,N-methylenebisacrylamide (NMBA), and the volume of the crosslinker accounts for 1.5% of the total volume of HEMA, NVP and KH-570. The initiator is preferably azobisisobutyronitrile (AIBN), and the volume of the initiator is preferably 0.7% of the total volume of the HEMA, NVP and KH-570. The mixing order of the HEMA, NVP, KH-570, the crosslinker and the initiator is preferably: premixing the HEMA, NVP and KH-570 to obtain a premixed solution; mixing the premixed solution, the crosslinker and the initiator. The reaction is preferably carried out under stirring, and the reaction time is preferably ≥30 min. The solid-liquid separation is preferably filtration. The present invention removes unreacted impurities through solid-liquid separation.

[0063] In the present invention, the structure of the mold for preparing the annular silicone hydrogel elastic film is as follows: Figure 3 As shown, the preparation mold for preparing the annular silicone hydrogel elastic film includes an upper mold 5 and a lower mold 3. The structure of the lower mold 3 for preparing the annular silicone hydrogel elastic film is the same as that of the lower mold 3 for preparing the corneal contact lens. The difference between the structure of the upper mold 5 for preparing the annular silicone hydrogel elastic film and the structure of the lower mold 4 for preparing the corneal contact lens is that: the vertex area of ​​the spherical convex surface of the upper mold 5 for preparing the annular silicone hydrogel elastic film is provided with an elevated spherical convex surface. The diameter of the spherical convex surface of the upper mold 5 for preparing the annular silicone hydrogel elastic film is D, the annular width of the annular silicone hydrogel elastic film is d, and the diameter of the elevated spherical convex surface is D-2d. The present invention changes the structure of the spherical convex surface of the upper mold 5 for preparing the annular silicone hydrogel elastic film by raising the spherical convex surface, and raises the height of the spherical surface area with a middle diameter of D-2d on the surface of the upper mold 5 for preparing the annular silicone hydrogel elastic film, so that it can be close to the inner position of the concave surface of the lower mold, thereby obtaining an annular silicone hydrogel elastic film.

[0064] The present invention preferably drips a sufficient amount of the first silicone hydrogel precursor solution into the lower mold for preparing the annular silicone hydrogel elastic film, uses the upper mold for preparing the annular silicone hydrogel elastic film to cover the lower mold for preparing the annular silicone hydrogel elastic film, distributes the first silicone hydrogel precursor solution between the upper and lower molds for preparing the annular silicone hydrogel elastic film, and then performs the first curing.

[0065] In the present invention, the first curing is preferably carried out in a constant temperature box, and the first curing preferably includes first stage curing and second stage curing in sequence, the temperature of the first stage curing is preferably 65°C, and the time is preferably 20 minutes; the temperature of the second stage curing is preferably 75°C, and the time is preferably 36 minutes. After the curing is completed, the present invention preferably immerses the first molded product obtained after demoulding in a NaCl aqueous solution for hydration to obtain a ring-shaped silicone hydrogel elastic film. The mass percentage of the NaCl aqueous solution is preferably 0.9%. The hydration time is preferably 15 minutes.

[0066] After obtaining the annular silicone hydrogel elastic film, the present invention dopes the annular silicone hydrogel elastic film to obtain an annular silicone hydrogel elastic film initially doped with gold nanoparticles; the doping includes sequentially etching and impregnation, the etching is wet etching, and the impregnation is performed using a gold nanoparticle aqueous dispersion.

[0067] In the present invention, the doping is preferably repeated, and the number of times the doping is repeated is preferably 5 to 6 times. When each doping is performed, the reagent used for the wet etching is acetone. The present invention preferably adopts an immersion method to perform the wet etching, and the specific implementation method of the wet etching is preferably: immersing the annular silicone hydrogel elastic film or the annular silicone hydrogel elastic film after several doping in the reagent used for wet etching for etching. The etching time for one doping is preferably 1 to 3 minutes, specifically 2 minutes. In the present invention, the immersion is preferably to immerse the etched film in a gold nanoparticle aqueous dispersion to dope the gold nanoparticles. The immersion time for one doping is preferably 5 to 10 minutes.

[0068] After obtaining the annular silicone hydrogel elastic film initially doped with gold nanoparticles, the present invention places the annular silicone hydrogel elastic film initially doped with gold nanoparticles and a silicone hydrogel precursor solution (hereinafter referred to as the second silicone hydrogel precursor solution) in a mold for preparing a corneal contact lens for curing (hereinafter referred to as the second curing) to obtain the gold nanoparticle-silicone hydrogel corneal contact lens.

[0069] In the present invention, the preparation method of the second silicone hydrogel precursor solution is the same as the preparation method of the first silicone hydrogel precursor solution, which will not be described in detail herein.

[0070] The present invention has no special requirements for the preparation mold of corneal contact lenses, and the preparation mold of corneal contact lenses (contact lenses) well known to those skilled in the art can be used, such as Figure 2 As shown, the mold for preparing corneal contact lenses in the present invention includes an upper mold 4 and a lower mold 3, the upper mold 4 of the mold for preparing corneal contact lenses is convex, and the lower mold 3 of the mold for preparing corneal contact lenses is concave, the upper mold 4 and the lower mold 3 of the mold for preparing corneal contact lenses are matched with each other in structure, and the upper mold 4 and the lower mold 3 of the mold for preparing corneal contact lenses are squeezed against each other to form a mold cavity between the upper and lower mold surfaces.

[0071] In the present invention, when preparing the gold nanoparticle-silicone hydrogel contact lens, the present invention preferably first places the annular silicone hydrogel elastic film initially doped with gold nanoparticles in the lower mold of the contact lens preparation mold, and then drops a sufficient amount of the second silicone hydrogel precursor solution into the lower mold of the contact lens preparation mold, uses the upper mold of the contact lens preparation mold to cover the lower mold of the contact lens preparation mold, distributes the second silicone hydrogel precursor solution between the upper and lower molds of the contact lens preparation mold, and then performs the second curing.

[0072] In the present invention, the second curing is preferably carried out in a constant temperature box, and the second curing preferably includes sequentially carrying out the first stage curing and the second stage curing, the temperature of the first stage curing is preferably 65°C, and the time is preferably 20 minutes; the temperature of the second stage curing is preferably 75°C, and the time is preferably 36 minutes. After the curing is completed, the present invention preferably immerses the second molded product obtained after demolding in a NaCl aqueous solution for hydration to obtain the gold nanoparticle-silicone hydrogel corneal contact lens. The mass percentage of the NaCl aqueous solution is preferably 0.9%. The hydration time is preferably 15 minutes.

[0073] The present invention provides the use of the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution in intraocular pressure detection.

[0074] The present invention provides the use of the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution in preparing an intraocular pressure detection device.

[0075] The present invention provides a visual intraocular pressure detection method, comprising the following steps:

[0076] Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be tested;

[0077] The color change of the annular detection area of ​​the gold nanoparticle-silicone hydrogel corneal contact lens is observed. When the color of the annular detection area becomes lighter, the intraocular pressure of the eye to be detected increases.

[0078] The present invention provides a method for qualitatively detecting intraocular pressure, comprising the following steps:

[0079] Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be tested;

[0080] An optical fiber spectrometer is used to collect spectral data of the annular detection area of ​​the gold nanoparticle-silicone hydrogel corneal contact lens, and the change in intraocular pressure of the eye is analyzed based on the change in the wavelength of the characteristic absorption peak of the spectral data. When the wavelength of the characteristic absorption peak of the spectral data moves in a gradually decreasing direction, the intraocular pressure of the eye to be detected increases; the characteristic absorption peak of the spectral data is the surface plasmon resonance (SPR) peak of the gold nanoparticles.

[0081] The present invention provides a method for quantitatively detecting intraocular pressure, comprising the following steps:

[0082] Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be tested;

[0083] Using a fiber optic spectrometer to collect spectral data of the annular detection area of ​​the gold nanoparticle-silicone hydrogel contact lens;

[0084] The intraocular pressure to be detected is obtained according to the wavelength of the characteristic absorption peak of the spectral data and the quantitative relationship between the intraocular pressure and the wavelength of the characteristic absorption peak; the characteristic absorption peak of the spectral data is the surface plasma resonance peak of the gold nanoparticles. In the present invention, the quantitative relationship between the intraocular pressure and the characteristic absorption peak wavelength is a functional relationship with the intraocular pressure as the independent variable and the wavelength of the characteristic absorption peak of the spectral data in the annular detection area as the dependent variable.

[0085] The present invention provides a method for quantitatively detecting intraocular pressure, comprising the following steps:

[0086] Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in the above technical solution or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in the above technical solution on the part of the eyeball to be tested;

[0087] collecting an optical image of the annular detection area of ​​the gold nanoparticle-silicone hydrogel contact lens;

[0088] The intraocular pressure to be detected is obtained according to the chromaticity information in the optical image and the quantitative relationship between the intraocular pressure of the eye and the chromaticity information of the annular detection area. In the present invention, the quantitative relationship between the intraocular pressure of the eye and the chromaticity information of the annular detection area is a functional relationship with the intraocular pressure of the eye as the independent variable and the chromaticity information of the annular detection area as the dependent variable.

[0089] The gold nanoparticle-silicon hydrogel corneal contact lens provided by the present invention can be worn on the cornea of ​​animals and humans without affecting the visual axis area, and can realize non-invasive real-time intraocular pressure monitoring, which is of great practical significance for the screening, diagnosis and treatment of glaucoma.

[0090] The present invention applies a silicone hydrogel elastic film embedded with gold nanoparticles to the preparation of corneal contact lenses and intraocular pressure detection. The silicone hydrogel colloid can quantify nanoscale tensile deformation and has excellent biocompatibility, so it can be used for high-sensitivity sensing of micro-deformation of the cornea of ​​the eyeball.

[0091] The present invention utilizes a polymer film of gold nanoparticles-silicon hydrogel to produce a color response visible to the naked eye to changes in intraocular pressure, which can not only directly determine the approximate range of the wearer's actual intraocular pressure, but also perform accurate quantitative analysis through image processing methods.

[0092] In order to further illustrate the present invention, the technical solutions provided by the present invention are described in detail below in conjunction with embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0093] Example 1

[0094] The preparation of the silica hydrogel precursor solution comprises the following steps:

[0095] Step 1: Hydroxyethyl methacrylate (HEMA), N-vinyl pyrrolidone (NVP), and Y-(methacryloyloxy)propyltrimethoxysilane (KH-570) are placed in a beaker at a volume ratio of 8.5:1:0.5 to obtain a premixed solution, and then a crosslinker N,N-methylenebisacrylamide (NMBA) and an initiator azobisisobutyronitrile (AIBN) are added, the volume of NMBA is 1.5% of the volume of the premixed solution, and the volume of AIBN is 0.7% of the volume of the premixed solution to obtain a mixed solution;

[0096] Step 2: Stir the mixed solution obtained in step 1 with a magnetic stirrer at room temperature for 30 minutes.

[0097] Step 3: Filter the uniformly stirred mixed solution to remove unreacted impurities to obtain a silicon hydrogel precursor solution.

[0098] The preparation of the annular silicone hydrogel elastic film doped with gold nanoparticles comprises the following steps:

[0099] Use a pipette to transfer enough amount of the prepared silicone hydrogel precursor solution into the Figure 3 In the lower mold of the mold for preparing the annular silicone hydrogel elastic film doped with gold nanoparticles, the center diameter of the convex surface at the top of the lower mold is 6 mm, the center diameter of the convex surface at the edge is 12 mm, and the width of the prepared annular film is 3 mm. Then the upper mold in the mold for preparing the annular silicone hydrogel elastic film doped with gold nanoparticles is vertically closed downward, and then cured at 65°C for 20 minutes and 75°C for 35 minutes in a constant temperature box. After cooling, the mold is taken out, and the upper and lower molds are separated by mechanical external force. After the middle film is demolded, it is immersed in 0.9% saline for 15 minutes until it is completely hydrated and becomes a soft annular silicone hydrogel transparent film.

[0100] The annular silicone hydrogel transparent film was placed in 10 mL of acetone solution and soaked for 2 minutes, and then placed in the gold nanoparticle aqueous dispersion and soaked for 5 minutes. After being taken out, the above process was repeated 5 to 6 times until the gold nanoparticles fully entered the annular silicone hydrogel transparent film, and an annular silicone hydrogel elastic film doped with gold nanoparticles (such as Figure 1 The thickness of the annular silicone hydrogel elastic film doped with gold nanoparticles is 0.15 mm.

[0101] The production of gold nano-silicone hydrogel contact lenses involves the following steps:

[0102] The prepared annular silicone hydrogel elastic film doped with gold nanoparticles was spread flat on the Figure 2 In the lower mold shown, a sufficient amount of silicone hydrogel precursor solution is taken into the lower mold to ensure that the annular area can be sealed in the silicone hydrogel precursor solution; finally, the upper and lower molds are squeezed and matched, and placed in a constant temperature box to cure at 65°C for 20 minutes and 75°C for 35 minutes. After cooling, the mold is taken out, and the upper and lower molds are separated by mechanical external force. The molded product is immersed in 0.9% saline for 15 minutes until it is completely hydrated and becomes a soft film, thereby obtaining a gold nano-silicone hydrogel corneal contact lens.

[0103] The thickness of the annular silicone hydrogel elastic film doped with gold nanoparticles prepared in this embodiment is 0.15 mm. The thickness of the pupil area of ​​the finished corneal contact lens film is 0.2 mm.

[0104] The gold nano-silicon hydrogel corneal contact lens prepared in this embodiment retains the high water content and high oxygen permeability of the silicone hydrogel contact lens, ensures the comfort and reliability of the wearing process, effectively prevents problems such as dry eyes and hypoxia, and is suitable for long-term wear. The annular film containing gold nanoparticles is placed 3mm outside the contact lens, does not block the pupil, and does not affect the field of vision.

[0105] The preparation method of the blank film comprises the following steps:

[0106] Take a sufficient amount of the silicone hydrogel precursor solution and place it in Figure 2 The upper and lower molds are squeezed and matched, and placed in a constant temperature box and cured at 65°C for 20 minutes and 75°C for 35 minutes. After cooling, the molds are taken out and the upper and lower molds are separated by mechanical force. The molded product is immersed in 0.9% saline for 15 minutes until it is completely hydrated and becomes a soft film to obtain a blank corneal contact lens.

[0107] Figure 7 This is a physical picture of a corneal contact lens prepared according to an embodiment of the present invention. Figure 7 The picture above shows a transparent silicone hydrogel film (blank film). The actual color is transparent and light yellow. Figure 7 The picture below shows a silicone hydrogel film with gold nanoparticles added. The actual color is transparent pink.

[0108] In order to demonstrate the feasibility of using the gold nano-silicone hydrogel corneal contact lens prepared in Example 1 to detect intraocular pressure, the present invention provides the following Example 2, and Example 2 provides a theoretical basis for the subsequent use of the gold nano-silicone hydrogel corneal contact lens prepared in Example 1 to prepare a portable visual intraocular pressure detection device.

[0109] Example 2

[0110] like Figure 4 As shown, this embodiment provides a method for using gold nanoparticle-silicone hydrogel corneal contact lens to detect human intraocular pressure, comprising the following steps:

[0111] Step 1: Turn on the light source (do not have strong ambient light during the experiment), connect the light source to one end of the 330-1050nm fiber optic spectrometer used, and connect the other end of the fiber optic spectrometer to the computer.

[0112] Step 2: Wear the gold nanoparticle-silicon hydrogel corneal contact lens prepared in Example 1 on a simulated eyeball in the laboratory (the simulated eyeball is simulated according to the proportion of the human eye. It mainly simulates the thickness of the cornea and the radius of corneal curvature. The main effect is to fit the corneal contact lens made in the experiment), ensure that the contact lens is worn correctly and adjusted to the appropriate position to ensure comfort and safety. Open the detection program of the fiber optic spectrometer and select the dark spectrum.

[0113] Step 3: Aim the light probe of the light source at the area containing gold nanoparticles on the outside of the contact lens. Minimize direct contact between the fiber optic probe and the eye and ensure that the position of the fiber optic probe is stable and consistent.

[0114] Step 4: Collect data (use LabVIEW software for data collection and description), subtract the background spectrum data from the spectrum data of wearing contact lenses to obtain the net absorption spectrum. Analyze the characteristic peaks of the spectrum curve and the surface plasmon resonance (SPR) peak of gold nanoparticles.

[0115] Step 5: Select different time periods, repeatedly measure the spectral data, and record the peak value of the SPR peak.

[0116] This embodiment records the peak value of the initial measurement, repeatedly measures the spectrum at different time periods, and compares the movement of the peak value. If the peak value moves in the direction of gradually decreasing wavelength, the distance between the gold nanoparticles gradually increases, the eyeball expands, and the intraocular pressure is in an elevated state at this moment.

[0117] The blank film prepared in Example 1 and the same area (annular area) of the gold nanoparticle-silicone hydrogel corneal contact lens were tested according to the steps of Example 2. The results are as follows: Figure 5 shown. Figure 5 The sinking curve in the figure is when visible light is irradiated onto the surface of the annular area of ​​the silicone hydrogel film containing gold nanoparticles. Most of the light is absorbed and part is scattered, which is due to the SPR effect of the gold nanoparticles contained inside. Figure 5 It shows that there is very obvious light absorption in the annular area of ​​the visible spectrum at 530-550nm; the blue area reflects the light intensity absorption under the comparison of the two spectral lines.

[0118] Depend on Figure 5 It shows that the gold nanoparticle-silicone hydrogel corneal contact lens prepared in Example 1 of the present invention contains gold nanoparticles, and its absorption peak changes significantly with the change of intraocular pressure. In addition, as the intraocular pressure increases and the eyeball expands, it is a large spacing change for the gold nano microparticles, and the drift degree of its relative absorption peak will be greater, which is enough to illustrate its sensitivity. Therefore, the gold nanoparticle-silicone hydrogel corneal contact lens provided by the present invention has high sensitivity and accuracy in intraocular pressure monitoring, and the unique optical and electrical properties of gold nanoparticles enable it to detect tiny pressure changes, thereby providing accurate intraocular pressure measurement results.

[0119] Figure 6 Spectral comparison of the gold nano-silicon hydrogel film prepared in Example 1 under simulated elevated intraocular pressure. Figure 6 The experimental method is the same as that in Example 2. Figure 6The three curves in the figure correspond to the spectral scattering of the silicon hydrogel film containing gold nanoparticles under three states of gradual expansion. They are equivalent to the spectral drift diagrams under pressures of 10mmHg, 14mmHg, and 18mmHg, respectively, and are used to simulate the situation of increased intraocular pressure. Figure 6 It can be seen that as the simulated intraocular pressure increases, the coupling effect between gold nanoparticles weakens, and the spectral absorption peak gradually drifts in the direction of decreasing wavelength, which is the blue shift phenomenon. The absorption peak intensity decreases with increasing spacing, which is manifested as the spectrum line drifting to the upper left.

[0120] Example 3

[0121] like Figure 4 As shown, this embodiment provides a method for using gold nanoparticle-silicone hydrogel corneal contact lens to detect human intraocular pressure, comprising the following steps:

[0122] Step 1: Turn on the light source (do not have strong ambient light during the experiment), connect the light source to one end of the 330-1050nm fiber optic spectrometer used, and connect the other end of the fiber optic spectrometer to the computer.

[0123] Step 2: The subject wears the gold nanoparticle-silicone hydrogel corneal contact lens prepared in Example 1, ensuring that the contact lens is worn correctly and adjusted to a suitable position to ensure comfort and safety. The detection program of the fiber optic spectrometer is turned on, and the dark spectrum is selected.

[0124] Step 3: Aim the light probe of the light source at the area containing gold nanoparticles on the outside of the contact lens. Minimize direct contact between the fiber optic probe of the light source and the eye, and ensure that the position of the fiber optic probe is stable and consistent.

[0125] Step 4: Collect data, subtract the background spectrum data from the spectrum data of the contact lens, and obtain the net absorption spectrum. Analyze the characteristic peaks of the spectrum curve, the surface plasmon resonance (SPR) peak of the gold nanoparticles.

[0126] Step 5: Select different time periods, repeatedly measure the spectral data, and record the peak value of the SPR peak.

[0127] This embodiment records the peak value of the initial measurement, repeatedly measures the spectrum at different time periods, and compares the movement of the peak value. If the peak value moves in the direction of gradually decreasing wavelength, the distance between the gold nanoparticles gradually increases, the eyeball expands, and the intraocular pressure is in an elevated state at this moment.

[0128] From the above examples, it can be seen that the intraocular pressure monitoring method implemented by the gold nanoparticle-silicone hydrogel corneal contact lens provided by the present invention has high sensitivity and accuracy. The unique optical and electrical properties of gold nanoparticles enable it to detect tiny pressure changes, thereby providing accurate intraocular pressure measurement results. Silicone hydrogel materials have excellent biocompatibility and can be worn for a long time. Compared with traditional intraocular pressure detection methods, this material is non-invasive and portable, can reduce mechanical damage to the eyeball, and does not affect the wearer's vision and comfort. Therefore, the gold nanoparticle-silicone hydrogel corneal contact lens of the present invention shows broad application prospects in the field of intraocular pressure detection, and provides an innovative and efficient solution for eye health monitoring.

[0129] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A gold nanoparticle-silicone hydrogel corneal contact lens, characterized in that: including a middle pupil area and an annular detection area surrounding the middle pupil area; The middle pupil area is a silicone hydrogel elastic film; The annular detection area is an annular silicone hydrogel elastic film doped with gold nanoparticles.

2. The gold nanoparticle-silicone hydrogel contact lens according to claim 1, characterized in that: The annular silicone hydrogel elastic film doped with gold nanoparticles comprises an annular silicone hydrogel elastic film and gold nanoparticles doped in the annular silicone hydrogel elastic film, and the particle size of the gold nanoparticles is 30-50 nm.

3. The method for preparing the gold nanoparticle-silicone hydrogel corneal contact lens according to claim 1 or 2, characterized in that: The following steps are involved: (1) placing a silicone hydrogel precursor solution in a mold for preparing an annular silicone hydrogel elastic film for curing, and then demolding to obtain an annular silicone hydrogel elastic film; (2) doping the annular silicone hydrogel elastic film to obtain an annular silicone hydrogel elastic film initially doped with gold nanoparticles; the doping comprises etching and impregnation in sequence, the etching is wet etching, and the impregnation is performed using a gold nanoparticle aqueous dispersion; (3) placing the annular silicone hydrogel elastic film initially doped with gold nanoparticles and the silicone hydrogel precursor solution in a mold for preparing a corneal contact lens and curing them to obtain the gold nanoparticle-silicone hydrogel corneal contact lens.

4. The preparation method according to claim 3, characterized in that: The method for preparing the silicone hydrogel precursor solution used in step (1) and step (3) comprises the following steps: Hydroxyethyl methacrylate, N-vinyl pyrrolidone, Y-(methacryloyloxy)propyltrimethoxysilane, a crosslinking agent and an initiator are mixed and reacted to obtain a reaction liquid; The reaction liquid is separated into solid and liquid to obtain the silicon hydrogel precursor solution.

5. The preparation method according to claim 3, characterized in that: In step (2): the doping is repeated 5 to 6 times; When the doping is performed once, the etching time is 1 to 3 minutes, and the immersion time is 5 to 10 minutes; The etching agent used in the wet etching is acetone.

6. Use of the gold nanoparticle-silicone hydrogel corneal contact lens according to claim 1 or 2 or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method according to any one of claims 3 to 5 in intraocular pressure detection.

7. A visual intraocular pressure detection method, characterized in that: The following steps are involved: Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in claim 1 or 2 or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in any one of claims 3 to 5 on the part of the eyeball to be tested; The color change of the annular detection area of ​​the gold nanoparticle-silicone hydrogel corneal contact lens is observed. When the color of the annular detection area becomes lighter, the intraocular pressure of the eye to be detected increases.

8. A method for qualitative detection of intraocular pressure, characterized in that: The following steps are involved: Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in claim 1 or 2 or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in any one of claims 3 to 5 on the part of the eyeball to be tested; An optical fiber spectrometer is used to collect spectral data of the annular detection area of ​​the gold nanoparticle-silicone hydrogel corneal contact lens, and the change in intraocular pressure of the eye is analyzed based on the change in the wavelength of the characteristic absorption peak of the spectral data. When the wavelength of the characteristic absorption peak of the spectral data moves in a gradually decreasing direction, the intraocular pressure of the eye to be detected increases; the characteristic absorption peak of the spectral data is the surface plasma resonance peak of the gold nanoparticles.

9. A method for quantitatively detecting intraocular pressure, characterized in that: The following steps are involved: Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in claim 1 or 2 or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in any one of claims 3 to 5 on the part of the eyeball to be tested; Using a fiber optic spectrometer to collect spectral data of the annular detection area of ​​the gold nanoparticle-silicone hydrogel contact lens; The intraocular pressure to be detected is obtained according to the quantitative relationship between the wavelength of the characteristic absorption peak of the spectral data and the intraocular pressure-characteristic absorption peak wavelength; the characteristic absorption peak of the spectral data is the surface plasma resonance peak of the gold nanoparticles.

10. A method for quantitatively detecting intraocular pressure, characterized in that: The following steps are involved: Wearing the gold nanoparticle-silicone hydrogel corneal contact lens described in claim 1 or 2 or the gold nanoparticle-silicone hydrogel corneal contact lens prepared by the preparation method described in any one of claims 3 to 5 on the part of the eyeball to be tested; collecting an optical image of the annular detection area of ​​the gold nanoparticle-silicone hydrogel contact lens; The intraocular pressure of the eye to be detected is obtained according to the quantitative relationship between the chromaticity information in the optical image and the chromaticity information of the intraocular pressure-annular detection area.

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