Cornea embedded micro lens and preparation method and application thereof

Abstract

The invention belongs to the technical field of regenerative medicine, and provides a circular cornea embedded micro lens, which comprises two areas, namely a first correction area and a plano area, preferably comprises three areas, namely two vision correction areas and a plano area, the two vision correction areas have the vision correction effect, the diopter of the plano area is 0D, and the diopter of the first correction area is 0 D, and the diopter of the plano area is 0 D; wherein the flat light area is provided with a through hole, and the applicant summarizes and finds that the through hole is formed in the center of the cornea embedded microlens, so that the phenomena of nebula and turbidity of the cornea after operation can be reduced. After the cornea embedded microlens provided by the invention is implanted, a patient can clearly see near objects and distant objects, so that clear vision is realized. The invention further provides a preparation method and application of the cornea embedded microlens.

Description

Technical Field

[0001] The present invention belongs to the technical field of regenerative medicine. Specifically, the first aspect of the present invention relates to a cornea-embedded microlens product, the second aspect relates to a method for preparing the cornea-embedded microlens product, and the third aspect relates to the application of the cornea-embedded microlens in a product for correcting vision loss. Background Art

[0002] As we age, or due to bad eye habits, our vision will deteriorate. Presbyopia is a common vision problem. As we age, the elasticity of the lens of the human eye will gradually weaken after the age of 40, and the ability to adjust will also gradually weaken. This is the main cause of presbyopia, so people will have blurred vision when looking at close objects. The main symptoms of presbyopia are: 1. It is difficult to see very small fonts in a low-light environment; 2. When reading books or newspapers, keep a longer reading distance, and the eyes will feel more comfortable; 3. You cannot persist when writing, reading, and doing fine manual work; 4. When reading newspapers, it will be more comfortable to take off myopic glasses; 5. When buying things, it is easy to misread the price; 6. Compared with when you were young, you have higher requirements for the brightness of light when reading books or newspapers.

[0003] In addition to vision loss caused by an unhealthy lens, refractive error can also cause vision loss. For example, when the eye is in a relaxed state, parallel light enters the eye and focuses in front of the retina, which results in a clear image not being formed on the retina, which is called myopia. At this time, an eye examination will indicate the degree of myopia. When the eye is in a relaxed state, parallel light from the outside world enters the eye and its focus falls on the retina, forming a clear image. This is called emmetropia. If the focus cannot fall on the retina, it is called non-emmetropia, which is refractive error. Therefore, myopia is a symptom of refractive error.

[0004] Intraocular lenses are usually used to correct vision loss caused by unhealthy lens conditions. Intraocular lenses are usually inserted into the eye chamber, the capsular bag of the eye, or between the iris and the lens. US Patent Document US2004 / 0085511A1 discloses an intraocular lens for insertion into the posterior chamber of the eye.

[0005] Usually, an intracorneal lens is used to correct vision loss caused by refractive error. The intracorneal lens is inserted into the cornea instead of the eye chamber, so this lens is usually smaller than the intraocular lens. Because the positions of the intracorneal lens and the intraocular lens relative to the lens are different, the intracorneal lens and the intraocular lens must have different optical structures to correct vision loss. Chinese patent document CN101896853A discloses an intracorneal lens with a central hole.

[0006] In the prior art, there is no technology that uses a lens embedded in the cornea to simultaneously correct vision loss caused by an unhealthy state of the lens and vision loss caused by refractive errors. Summary of the invention

[0007] In order to make up for the shortcomings and deficiencies of the prior art, the first aspect of the present invention provides a cornea-embedded microlens, wherein the microlens is circular and includes two areas, namely a first correction area and a plano area, wherein the plano area is surrounded by the first correction area, the first correction area is concentric with the plano area, the first correction area has the function of correcting vision, the refractive power of the plano area is 0D, and the plano area has a through hole.

[0008] The cornea-embedded microlens provided by the present invention includes two areas, wherein the first correction area has the function of correcting vision, and the refractive power of the plano area is 0D, which does not have the function of correcting vision. The first correction area can be used to correct the visual impairment caused by the unhealthy state of the refractive medium, or to correct the visual impairment caused by refractive error. Although the plano area does not have the function of correcting vision, when looking at distant objects, it can make the light enter the eye in parallel, and then reach the retina, and form a clear image. Specifically, whether the first correction area is used to correct the visual impairment caused by the unhealthy state of the refractive medium, or to correct the visual impairment caused by refractive error, the plano area can make the light enter the eye in parallel, and then reach the retina, and form a clear image, thereby ensuring that the first correction area plays a role in correcting vision, and the light entering the eye through the plano area can maintain the patient's original visual adjustment ability, so that the patient's distance vision loss or compensation for near vision can be avoided. When the cornea-embedded microlens provided by the present invention is used, the specific shape of the first correction area and the plano area and the area ratio between the two can be changed according to the patient's vision symptoms, so as to correct the patient's vision loss symptoms to the greatest extent. It should be noted that the plano area has a through hole, and the through hole has two functions. The first aspect is to facilitate surgical marking. Specifically, since the cornea-embedded microlens provided by the present invention is usually required to have the center of the microlens on the visual axis during clinical application, otherwise it will affect the clinical use effect of corrected vision, and the through hole can provide an accurate reference position for the doctor performing the operation, which is convenient for finding the center of the microlens, and then accurately positioning the center of the microlens on the visual axis; secondly, after a large number of experiments, the applicant concluded that setting a through hole at the center of the cornea-embedded microlens can reduce the phenomenon of corneal clouding and turbidity after surgery.

[0009] In a preferred embodiment of the present invention, the plano area of ​​the corneal embedded microlens provided by the present invention includes a second correction area, the second correction area is circular and surrounded by the plano area, and the through hole is located in the second correction area. In this preferred embodiment, the corneal embedded microlens has three areas, namely two vision correction areas and one plano area, the two vision correction areas respectively have the function of correcting vision, and can be used to correct vision loss caused by the unhealthy state of the refractive medium, or to correct vision loss caused by refractive error. The two vision correction areas can also respectively correct vision loss caused by the above two reasons. Although the plano area does not have the function of correcting vision, it can make light enter the eye in parallel and reach the retina, thereby alleviating the first correction area and the second correction area from playing the role of correcting vision, and can also compensate for the unclear imaging caused by the self-adjustment function of the lens or the refractive system. It should be noted that the second correction area has a through hole, and the through hole has two functions. The first is to facilitate surgical marking. Specifically, since the corneal embedded microlens provided by the present invention is usually required to have the center of the microlens on the visual axis during clinical application, otherwise it will affect the clinical use effect of correcting vision, and the through hole can provide an accurate reference position for the doctor performing the operation, which is convenient for finding the center of the microlens, and then accurately positioning the center of the microlens on the visual axis; secondly, after a large number of experiments, the applicant concluded that setting a through hole at the center position of the corneal embedded microlens can reduce the phenomenon of corneal clouding and turbidity after surgery.

[0010] In a preferred embodiment of the present invention, the first correction zone of the cornea-embedded microlens provided by the present invention has the function of correcting vision loss caused by the unhealthy state of the refractive medium, and the second correction zone has the function of correcting vision loss caused by refractive error. The applicant has learned through a large number of experiments that although the first correction zone and the second correction zone can both have the function of correcting vision loss caused by the unhealthy state of the refractive medium and can also have the function of correcting vision loss caused by refractive error, when the first correction zone has the function of correcting vision loss caused by the unhealthy state of the refractive medium and the second correction zone has the function of correcting vision loss caused by refractive error, the cornea-embedded microlens provided by the present invention can simultaneously correct vision loss caused by the unhealthy state of the refractive medium and vision loss caused by refractive error, so that patients can achieve full vision after surgery. Specifically, the vision loss caused by the unhealthy state of the refractive medium will cause the patient to see distant objects clearly but near objects blurred, while the vision loss caused by refractive error will cause the patient to image objects in front of or behind the retina, resulting in blurred vision. Therefore, after the patient is surgically implanted with the corneal embedded microlens provided by the present invention, when looking at near objects, the cornea outside the first correction area is properly blocked due to the contraction of the iris and the reduction of the pupil. At this time, all light passing through the first correction area will be corrected, thereby compensating for the blurred vision caused by the unhealthy state of the refractive medium and the refractive error in the plano area and the second correction area, thereby making the postoperative The patient's vision becomes clearer when seeing near objects; when seeing distant objects, the iris stretches and the pupil expands, and the second correction zone and the plano zone will work simultaneously, making the patient's vision of distant objects clearer; and, because the ciliary muscle stretches when seeing distant objects, part of the light can enter the eye through the corneal area outside the edge of the first correction zone of the cornea-embedded microlens, thereby increasing the amount of light entering the eye. At the same time, due to the existence of the plano zone, the vision of medium-distance vision when seeing distant objects is retained. Through the above two aspects, the patient's vision of distant objects becomes clearer after surgery; in this way, the patient can see near objects clearly and distant objects clearly after surgery, and ultimately achieve full clear vision.

[0011] In a preferred embodiment of the present invention, the number of through holes of the cornea-embedded microlens provided by the present invention is 1, the through hole is circular and concentric with the second correction zone, and the second correction zone is concentric with the plano zone. The applicant has learned through a large number of experiments that there is no significant difference between multiple through holes and 1 through hole in reducing the postoperative corneal clouding and turbidity in the number of through holes located in the second correction zone; and when the arrangement order of the three areas of the cornea-embedded microlens is "from the center of the cornea-embedded microlens to the outside: the second correction zone, the plano zone, the first correction zone" (that is, the second correction zone is surrounded by the plano zone, and the plano zone is surrounded by the first correction zone), the cornea-embedded microlens can simultaneously correct the vision loss caused by the unhealthy state of the refractive medium and the vision loss caused by refractive error, so that the patient can achieve full vision after surgery. Specifically, the vision loss caused by the unhealthy state of the refractive medium will cause the patient to see distant objects clearly but near objects blurred, while the vision loss caused by refractive error will cause the patient to image objects in front of or behind the retina, resulting in blurred vision. Therefore, after the patient is surgically implanted with the corneal embedded microlens provided by the present invention, when looking at near objects, the first correction area is properly blocked due to the contraction of the iris and the shrinkage of the pupil. At this time, the light passing through the first correction area and the second correction area will be corrected, compensating for the blurred vision of the plano area caused by the unhealthy state of the refractive medium, thereby making the patient postoperatively When looking at near objects, it becomes clearer; when looking at distant objects, due to the expansion of the iris and pupil, the second correction zone and the plano area will work at the same time, making the patient's vision of distant objects clearer; and, due to the stretching of the ciliary muscle when looking at distant objects, part of the light can enter the eye through the area outside the edge of the first correction zone of the corneal embedded microlens, thereby increasing the light entering the eye. At the same time, due to the existence of the plano area, the vision of the middle distance when looking at distant objects is retained. Through the above two aspects, the patient's vision of distant objects becomes clearer after surgery; in this way, the patient can see near objects clearly and distant objects clearly after surgery, and finally achieve full vision. Therefore, after a large number of experiments, the applicant concluded that in this preferred embodiment, it plays a corrective role at the same time, especially for patients with both presbyopia and myopia.

[0012] In a non-limiting embodiment of the present invention, the vision loss caused by the unhealthy state of the refractive medium refers to the vision loss caused by the lack of accommodation power, incomplete turbidity and weakened elasticity of the lens, such as presbyopia, etc.; the vision loss caused by refractive error refers to the fact that parallel light rays cannot form a clear image on the retina after passing through the refractive system of the eye, but form an image in front of or behind the retina, such as hyperopia, myopia, astigmatism, etc. In this way, the first correction area and the second correction area of ​​the corneal embedded microlens provided by the present invention respectively have the function of correcting the above two types of vision loss, thereby enabling the patient to achieve full vision after surgery.

[0013] After a large number of experiments, the applicant concluded that when the cross-section of the first correction zone along the center direction of the annular curvature is a convex lens cross-section, it can effectively correct the vision loss caused by the unhealthy state of the refractive medium. This is because after the patient is surgically implanted with the corneal embedded microlens provided by the present invention, especially when the patient looks at near objects after the operation, the iris contracts and the pupil shrinks, causing the outside of the first correction zone to be properly blocked. At this time, the light passing through the first correction zone and the second correction zone will be corrected. At this time, the convex lens function of the first correction zone will compensate for the blurred vision caused by the unhealthy state of the refractive medium in the plano zone and the second correction zone, thereby making the patient's near objects clearer after the operation.

[0014] In a further preferred embodiment of the present invention, the cross section of the first correction zone along the center direction of the annular curvature is a convex lens cross section, and the cross section of the second correction zone along the center direction of the circular curvature is a concave lens cross section. In this embodiment, the cornea-embedded microlens provided by the present invention can effectively correct myopia caused by refractive error, in which near objects are clear but far objects are blurred. This is because, after the patient is surgically implanted with the cornea-embedded microlens provided by the present invention, especially when the patient sees far objects after the operation, first, due to the expansion of the iris and the pupil, the second correction zone, the plano zone and the first correction zone will work simultaneously, and due to the stretching of the ciliary muscle when seeing far objects, part of the light can pass through the second correction zone of the cornea-embedded microlens. First, the corneal area outside the edge of the correction zone enters the eye, so more light enters the eye; second: due to the existence of the plano zone, the original visual adjustment ability caused by the unhealthy state of the refractive medium is retained, thereby compensating for the mid-distance vision and the total amount of light entering the eye; third: because the cross-section of the second correction zone along the center of the circular curvature is a concave lens cross-section, the concave lens plays the role of correcting myopia, and the through hole is concentric with the second correction zone, which is equivalent to the optical center of the second correction zone (i.e., the concave lens) being the through hole, which can avoid the light reflection phenomenon caused by the thickness of the section, and thus avoid glare; due to the above three factors, the patient's vision of distant objects becomes clearer after surgery.

[0015] The applicant has concluded and found after a large number of experiments that when the cross section of the first correction zone along the center direction of the annular curvature is a convex lens cross section, the cross section of the second correction zone along the center direction of the circular curvature is a concave lens cross section, and the through hole is circular and concentric with the second correction zone, it is particularly suitable for patients with presbyopia caused by the unhealthy state of the refractive medium and myopia caused by refractive error. This is because presbyopia can cause patients to see distant objects clearly but near objects are blurred, while myopia can cause patients to see near objects clearly but distant objects are blurred. Therefore, after the patient is surgically implanted with the corneal embedded microlens provided by the present invention, when looking at near objects, the iris contracts and the pupil shrinks, causing the outside of the first correction zone to be appropriately blocked. At this time, the light passing through the first correction zone and the second correction zone will be corrected. At this time, the convex lens function of the first correction zone It will make up for the blurred vision caused by presbyopia in the plano area and the second correction area, so that the patient can see near objects more clearly after surgery; when looking at distant objects, the iris stretches and the pupil expands, and the concave lens of the second correction area, the convex lens of the plano area and the first correction area will work simultaneously, so that the patient can see distant objects more clearly; and, because the ciliary muscle stretches when looking at distant objects, part of the light can enter the eye through the area outside the edge of the first correction area of ​​the cornea-embedded microlens, thereby increasing the light entering the eye. At the same time, due to the existence of the plano area, the relatively clear middle-distance vision of presbyopic eyes when looking at distant objects is retained. Through the above two aspects, the cornea-embedded microlens provided by the present invention can make the patient see distant objects more clearly after surgery; in this way, the patient can see near objects clearly and distant objects clearly after surgery, and finally the patient can achieve full vision after surgery.

[0016] In a preferred embodiment of the present invention, the diameter of the cornea-embedded microlens is 2.5 to 5.5 mm, which is related to the size of the cornea of ​​the individual patient. The applicant has learned through a large number of experiments that the size of the embedding suitable for embedding in the human cornea is 2.5 to 5.5 mm in diameter and 25 to 63 μm in thickness. According to the correction principle of the partitioned corneal implant microlens provided by the present invention, when the diameter is 3.0 to 4.0 mm and the thickness is 25 to 55 μm, it is easier to achieve full vision.

[0017] In a preferred embodiment of the present invention, the number of the through holes is 1, and the through hole is located at the optical center of the concave lens, that is, the thinnest part of the concave lens in the second correction zone is 0 mm. The applicant has concluded through a large number of experiments that the diameter of the through hole is related to the phenomenon of corneal clouding and turbidity after surgery. When the doctor positions the center of the corneal embedded microlens (that is, the center of the second correction zone) on the visual axis during surgery, and when the through hole diameter is 0.01-0.6 mm, it is convenient to position the corneal embedded microlens on the visual axis during clinical transplantation, and at the same time, it can reduce the phenomenon of corneal clouding and turbidity after surgery.

[0018] In a non-limiting embodiment of the present invention, the applicant selected the preparation material of the corneal embedded microlens from the following aspects: first, transparency and biocompatibility; second, the corrective effect of the patient after transplantation; third, having appropriate hardness (brittleness) and being suitable for cutting before transplantation; fourth, hydration rate, that is, the time required for the adsorbed solute to reach a stable equilibrium concentration in the hydration solution; fifth, the release duration of the antibiotic after binding after surgery; the applicant concluded through a large number of experiments that when the preparation material is a copolymer of one or more of 2-phenoxyethyl acrylate, ethylene glycol dimethacrylate, methyl methacrylate, polymethyl methacrylate, styrene acrylate, and hydroxyethyl methacrylate, the above first to fourth conditions can be met, and when the preparation material is hydroxyethyl methacrylate and methyl methacrylate, all of the above five conditions can be met.

[0019] In a non-limiting preferred embodiment of the present invention, in order to reduce the damage of ultraviolet rays to other intraocular tissues, the applicant added azophenyl methacrylate to the preparation material of the corneal embedded microlens. In a non-limiting preferred embodiment of the present invention, 4-propyleneoxy-2-hydroxybenzophenone was added to the preparation material of the corneal embedded microlens. In a non-limiting preferred embodiment of the present invention, azophenyl methacrylate and 4-propyleneoxy-2-hydroxybenzophenone were added to the preparation material of the corneal embedded microlens at the same time. After a large number of experiments, the applicant concluded that adding one of azophenyl methacrylate and 4-propyleneoxy-2-hydroxybenzophenone alone, compared with adding a mixture of the two, adding 4-propyleneoxy-2-hydroxybenzophenone alone is better for the transparency, biocompatibility, sustained release of antibiotics and use effect after transplantation of the membrane embedded microlens.

[0020] The second aspect of the present invention provides a method for preparing a cornea-embedded microlens, comprising: step A. weighing one or more of hydroxyethyl methacrylate, 2-phenoxyethyl acrylate, ethylene glycol dimethacrylate, methyl methacrylate, polymethyl methacrylate, styrene acrylate, and hydroxyethyl methacrylate to prepare a mixed solution; step B. weighing azophenyl methacrylate and / or 4-propyleneoxy-2-hydroxybenzophenone, and adding them to the solution prepared in step A; stirring evenly and adding them to a mold; step C. drying at 80-120° C. for 4-8 hours to prepare a buckle material; and step D. cutting, polishing, and hydrating the buckle material to prepare a cornea-embedded microlens.

[0021] In a non-limiting embodiment of the present invention, the hydration solution used for hydration is a physiological saline solution containing antibiotics. Among the numerous materials for preparing corneal embedded microlenses, the applicant also examined the strength of adsorption and binding of these materials with antibiotics and the release rate of antibiotics when selecting materials for preparing corneal embedded microlenses and ultraviolet blockers, while ensuring safety for postoperative use.

[0022] The applicant has concluded through a large number of experiments that when hydroxyethyl methacrylate and methyl methacrylate are selected as the preparation material and 4-propyleneoxy-2-hydroxybenzophenone is selected as the ultraviolet blocker, the negative impact of ultraviolet rays on the unhealthy state of the refractive medium and the refractive error of the refractive system can be effectively reduced, thereby reducing the speed and degree of vision loss in patients, and all of the above five conditions can be met. The applicant has further concluded through a large number of experiments that when the mass percentage of hydroxyethyl methacrylate and methyl methacrylate is 3:1 and 4-propyleneoxy-2-hydroxybenzophenone is selected as the ultraviolet blocker, the antibiotic release time can exceed 18 hours, and no corneal opacity or microlens opacity is observed after surgery.

[0023] After a large number of experiments, the applicant found that when hydroxyethyl methacrylate and methyl methacrylate are selected as the preparation materials and 4-propyleneoxy-2-hydroxybenzophenone is selected as the UV blocker, the fusion of the two is relatively stable, no premature aging phenomenon is observed, and the softness after hydration is relatively suitable. At the same time, the antibiotic release time can exceed 18 hours, which can promote the recovery of corneal transparency and nerve plexus after surgery.

[0024] In a non-limiting embodiment of the present invention, the mold has a cylinder so that the preparation material of the cornea-embedded microlens has a through hole after being formed in the mold, and the cylinder of the mold corresponds to the through hole. After a large number of experiments, the applicant concluded that providing a through hole at the center of the cornea-embedded microlens can reduce the occurrence of clouding and turbidity in the patient's cornea after surgery.

[0025] In a non-limiting preferred embodiment of the present invention, the cylinder is perpendicular to the mold surface, and the connection portion between the cylinder and the mold has a circular curvature on a section along the axis of the cylinder, so that the cross section of the second correction area of ​​the solution after molding in the mold along the center of the circular curvature is a concave lens cross section. In this case, the second correction area of ​​the cornea-embedded microlens prepared using the above mold is a concave lens, and the optical center of the concave lens is the through hole.

[0026] In a non-limiting preferred embodiment of the present invention, the outer ring of the mold surrounding the second correction zone is a plane, so that the mixed liquid has a plano zone after being molded in the mold. At this time, the second correction zone of the cornea-embedded microlens prepared by the above mold is surrounded by the plano zone, and the plano zone is a plane.

[0027] In a non-limiting preferred embodiment of the present invention, the mold has a circular curvature on the section along the cylindrical axis direction on the outer ring surrounding the plano area, so that the cross section of the first correction area along the center direction of the circular curvature after the mixed liquid is molded in the mold is a convex lens cross section. At this time, the plano area of ​​the corneal embedded microlens prepared by the above mold is surrounded by the first correction area, and the first correction area is a convex lens.

[0028] In a non-limiting embodiment of the present invention, in the above-mentioned method for preparing corneal embedded microlenses, the hydration solution used in the hydration step is a physiological saline solution containing antibiotics. The hydration means: placing the cut and polished microlenses in a physiological saline solution, so that the microlenses absorb water and recover in an environment isotonic with the osmotic pressure of the human body, thereby making the corneal embedded microlenses soft and similar to the water content of the human cornea. The applicant has learned through a large number of experiments that the hydration solution used in the hydration process is a physiological saline solution containing antibiotics, which can make the antibiotics combine with the preparation materials of the corneal embedded microlenses in the environment of physiological saline, and when the microlenses are implanted in the patient's cornea, the antibiotics can be continuously released for more than 18 hours, so that the patient can reduce the amount of antibiotics taken after surgery, thereby avoiding the overall impact of taking antibiotics on the patient's body.

[0029] After a large number of experiments, the applicant concluded that when the hydration solution contains, in addition to antibiotics, one or more of chondroitin sulfate, dextran 70 or hydroxypropyl methylcellulose E4M, and one or more of bFGF, VB6, and VB12, the rabbit eye transplantation experiment proved that the rabbit eye can always remain completely transparent, and the morphological characteristics of the rabbit eye's nerve plexus 3 months after surgery are similar to those before surgery.

[0030] In a preferred embodiment of the present invention, when the hydrated solution contains tobramycin, its concentration is 3 mg / ml, when it contains chondroitin sulfate, its concentration is 1 mg / ml, when it contains dextran 70, its concentration is 1 mg / ml, when it contains hydroxypropyl methylcellulose E4M, its concentration is 3 mg / ml, when it contains bFGF, its concentration is 4000 IU / ml, when it contains VB6, its concentration is 50 mg / ml, and when it contains VB12, its concentration is 0.2 mg / ml.

[0031] In a non-limiting preferred embodiment of the present invention, after the cornea-embedded microlens is prepared by the method for preparing the cornea-embedded microlens provided by the present invention, the cornea is preferably placed in a solution containing the components contained in the hydration solution during the subsequent storage and transportation of the cornea-embedded microlens. That is, whatever hydration solution is used in the preparation of the cornea-embedded microlens, the cornea is placed in a solution containing all the components contained in the hydration solution during the storage and transportation. The applicant has found that this can ensure that the antibiotics and other components adsorbed by the cornea will not be diluted when it is used, thereby ensuring that these components can play a role after surgery.

[0032] In a non-limiting preferred embodiment of the present invention, the mold is circular, the diameter of the mold is 10-18 mm, and the thickness of the mold is 3-8 mm. Since the larger the size of the buckle material made by the mold, the more material needs to be cut and removed when the cornea embedded microlens is obtained in the cutting step, which not only generates material waste, but also reduces the cutting efficiency, thereby affecting the production efficiency of the cornea embedded microlens product. However, the applicant has learned through a large number of experiments that when the diameter of the mold is 10-18 mm and the thickness of the mold is 3-8 mm, material waste can be reduced while taking into account production efficiency.

[0033] The third aspect of the present invention provides the use of a cornea-embedded microlens in a product for correcting vision loss caused by an unhealthy state of a refractive medium. The third aspect of the present invention also provides the use of a cornea-embedded microlens in a product for correcting vision loss caused by ametropia.

[0034] The cornea-embedded microlens provided by the present invention includes two areas and a through hole. Since the first correction area has the function of correcting the visual impairment caused by the unhealthy state of the refractive medium, or has the function of correcting the visual impairment caused by refractive error, and the refractive power of the plano area is 0D, after the patient is implanted with the cornea-embedded microlens, no matter whether the first correction area is used to correct the visual impairment caused by the unhealthy state of the refractive medium or to correct the visual impairment caused by refractive error, the plano area can make the light enter the eye in parallel, reach the retina, and form a clear image, thereby ensuring that the first correction area plays a role in correcting vision, and the light entering the eye through the plano area can maintain the patient's original visual adjustment. After a large number of experiments, the applicant concluded that setting a through hole at the center of the cornea-embedded microlens can not only facilitate surgical marking, but also reduce the phenomenon of corneal clouding and turbidity after surgery.

[0035] In a preferred embodiment of the present invention, the plano area of ​​the cornea-embedded microlens also includes a second correction area. In this case, the cornea-embedded microlens has three areas, namely, two vision correction areas and one plano area. From the center of the cornea-embedded microlens to the outside, they are: the second correction area, the plano area, and the first correction area, that is, the second correction area is surrounded by the plano area, and the plano area is surrounded by the first correction area. Although the plano area between the two correction areas does not have the function of correcting vision, it can allow light to enter the eye in parallel and reach the retina, thereby alleviating the vision correction function of the first correction area while compensating for the unclear imaging caused by the self-adjustment function of the lens or the refractive system. In particular, after implantation in the patient's non-dominant eye, when viewing near objects, the iris contracts and the pupil shrinks, and the outside of the first correction zone is appropriately blocked. At this time, all light passing through the first correction zone will be corrected, thus compensating for the blurred vision caused by the unhealthy state of the refractive medium and the refractive error in the plano zone and the second correction zone, thereby making the patient's near objects clearer after surgery; when viewing distant objects, the iris stretches and the pupil expands, and the second correction zone and the plano zone will work at the same time. Due to the stretching of the ciliary muscle, part of the light can enter the eye through the area outside the edge of the first correction zone of the cornea-embedded microlens, thereby increasing the light entering the eye, and at the same time Due to the existence of the plano area, the vision of the intermediate distance when viewing distant objects is retained. Through the above two aspects, the non-dominant eye of the patient after surgery can view distant objects more clearly. In addition, when the human body views objects with both eyes, when the clarity of vision of the two eyes is different (the eye with clear imaging is the dominant eye, and the eye with relatively unclear imaging is the non-dominant eye), the human body will actively select the image with clear imaging as the main imaging, and will appropriately ignore the visual perception of unclear imaging. Therefore, after the corneal embedded microlens provided by the present invention is implanted into the non-dominant eye of the patient, the patient can see near objects clearly and distant objects clearly after surgery, and finally achieve full clear vision. Please see the attached diagram for the simulation of the visual effect. Figure 5 . BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Attached Figure 1 An enlarged schematic diagram of the cornea-embedded microlens provided by the present invention

[0037] Attached Figure 2 Vertical cross-sectional views of the cornea-embedded microlens provided by the present invention (four examples) passing through the optical center

[0038] Attached Figure 3 The working principle diagram of the corneal embedded microlens provided in Example 10 of the present invention when implanted into the patient's cornea to look at near objects is as follows Figure 4 The working principle diagram of the corneal embedded microlens provided in Example 10 of the present invention when implanted into the patient's cornea to see distant objects is as follows Figure 5 The following is a simulation diagram of the binocular vision effect after the corneal embedded microlens provided in Example 11 of the present invention is implanted into the patient's cornea. Figure 6Flow chart of the method for preparing the cornea-embedded microlens provided by the present invention DETAILED DESCRIPTION

[0039] In order to accurately describe and illustrate the technical solution provided by the present invention, the technical terms used in the present invention are explained as follows before the content of the invention.

[0040] The "cornea-embedded microlens" mentioned in the present invention refers to a film that can be embedded in the corneal stroma layer and can correct vision.

[0041] The term "concentric" as used in the present invention refers to a situation where the centroids or centers (such as circles) of two or more regions coincide with each other.

[0042] The "optical center" mentioned in the present invention refers to the optical center in the physical sense. For example, the optical center of a concave lens is the point where the centers of the two refractive surfaces coincide. The characteristic of the optical center is that the propagation direction of light passing through this point remains unchanged.

[0043] The "curvature" mentioned in the present invention refers to the curvature of a curve in the mathematical sense, which is a numerical value indicating the degree of curvature of the curve at a certain point. The greater the curvature, the greater the degree of curvature of the curve.

[0044] The "concave lens" described in the present invention is a concave lens in the sense of optical terminology, that is, the lens is thin in the middle and thick at the edge, and is concave. The concave lens described in the present invention includes one side being a flat surface and the other side being a concave surface, and also includes both sides being concave surfaces.

[0045] The "convex lens" described in the present invention is a convex lens in the sense of optical terminology, that is, the lens is thick in the middle and thin at the edge, and is convex. The convex lens described in the present invention includes one side being a flat surface and the other side being a convex surface, and also includes both sides being convex surfaces. The convex lens is a complete convex lens along the direction perpendicular to the main optical axis, and also includes an incomplete convex lens along the direction perpendicular to the main optical axis, including a convex lens along the direction perpendicular to the main optical axis that is a half convex lens and at this time the thickest part of the convex lens is the same as the thickness of the flat optical area.

[0046] The "refractive medium" mentioned in the present invention refers to the refractive medium in the medical sense, such as the lens and vitreous body.

[0047] The "unhealthy state of the refractive medium" mentioned in the present invention refers to the visual impairment caused by the lack of accommodation power, incomplete opacity and weakened elasticity of the lens, such as presbyopia.

[0048] The "refractive error" mentioned in the present invention refers to the fact that after parallel light rays pass through the refractive effect of the eye, they cannot form a clear image on the retina, but form an image in front of or behind the retina.

[0049] The "visual impairment" mentioned in the present invention refers to the phenomenon that compared with the normal visual acuity of 1.0, the visual acuity becomes blurred when the visual acuity is lower than 1.0 as shown in the visual acuity test, making it difficult to distinguish small or distant objects.

[0050] The "mold" mentioned in the present invention refers to the mold and tool used to make shaped objects in industrial production, that is, the tool that makes the blank become a product with a specific shape and size under the action of external force.

[0051] The "VB12" mentioned in the present invention refers to vitamin B12.

[0052] The "bFGF" mentioned in the present invention refers to basic fibroblast growth factor.

[0053] The following non-limiting embodiments of the present invention are further described in conjunction with the accompanying drawings, wherein experimental rabbits are used instead of human patients to illustrate the various parameters of the corneal embedded microlens provided by the present invention and the specific steps of the preparation method. It should be stated that the following specific embodiments are only for illustrative purposes and should not be construed as limiting the technical solution of the present invention.

[0054] Example 1

[0055] This embodiment illustrates a cornea-embedded microlens, the microlens is circular, and includes two areas, namely a first correction area and a plano area, the plano area is surrounded by the first correction area, the first correction area is concentric with the plano area, the first correction area has the function of correcting vision, the refractive power of the plano area is 0D, and the plano area has a through hole. The first correction area can be used to correct vision loss caused by the unhealthy state of the refractive medium, or to correct vision loss caused by refractive error, and the plano area does not have the function of correcting vision. When the cornea-embedded microlens provided in this embodiment is used, the specific shape of the first correction area and the area ratio between the two can be changed according to the patient's vision symptoms, so as to correct the patient's vision loss symptoms to the greatest extent.

[0056] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0057] Example 2

[0058] This embodiment illustrates a cornea-embedded microlens. On the basis of Embodiment 1, the microlens includes two areas, "a first correction area and a plano area", wherein the first correction area has the function of correcting vision loss caused by the unhealthy state of the refractive medium, and the plano area does not have the function of correcting vision. The plano area is a circle with a diameter of 2 mm, and the thickness of the plano area is 25 μm; outside the plano area is an annular first correction area, the thickness of the inner circumference of the annular first correction area is the same as that of the plano area, and the outer diameter of the first correction area is 4 mm (i.e., the diameter of the cornea-embedded microlens). The maximum thickness of the cornea-embedded microlens is 54 μm.

[0059] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0060] Example 3

[0061] This embodiment illustrates a cornea-embedded microlens. On the basis of Embodiment 1, the cornea-embedded microlens has three regions, namely, "two correction regions and one plano region". The three regions are arranged in the following order, from the center of the cornea-embedded microlens outward: the second correction region, the plano region, and the first correction region. The first correction region has the function of correcting vision loss caused by the unhealthy state of the refractive medium, the plano region does not have the function of correcting vision, and the second correction region has the function of correcting vision loss caused by refractive error. The cornea-embedded microlens is circular, wherein the second correction zone is a circle with a diameter of 1.5 mm, and the thickest part of the second correction zone is 30 μm; outside the second correction zone is an annular plano zone, and the outer diameter of the plano zone is 2.5 mm; the thickness of the plano zone is the same as the thickness of the edge of the second correction zone; outside the plano zone is an annular first correction zone, and the outer diameter of the first correction zone is 4.5 mm (i.e., the diameter of the cornea-embedded microlens), and the thickness of the inner circumference of the annular first correction zone is the same as the thickness of the plano zone.

[0062] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0063] Example 4

[0064] This embodiment illustrates a cornea-embedded microlens. On the basis of Embodiment 1, the cornea-embedded microlens has three regions, namely, "two correction regions and one plano region". The three regions are arranged in the following order, from the center of the cornea-embedded microlens outward: the second correction region, the plano region, and the first correction region. The first correction region has the function of correcting vision loss caused by the unhealthy state of the refractive medium, the plano region does not have the function of correcting vision, and the second correction region also has the function of correcting vision loss caused by the unhealthy state of the refractive medium. The cornea-embedded microlens is circular, wherein the second correction zone is a circle with a diameter of 2 mm, and the thickest part of the second correction zone is 42 μm; outside the second correction zone is an annular plano zone, and the outer diameter of the plano zone is 3 mm; the thickness of the plano zone is the same as the thickness of the edge of the second correction zone; outside the plano zone is an annular first correction zone, and the outer diameter of the first correction zone is 4.2 mm (i.e., the diameter of the cornea-embedded microlens), and the thickness of the inner circumference of the annular first correction zone is the same as the thickness of the plano zone.

[0065] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0066] Example 5

[0067] This embodiment illustrates a cornea-embedded microlens. On the basis of Embodiment 1, the cornea-embedded microlens has three regions, namely, "two correction regions and one plano region". The three regions are arranged in the following order, from the center of the cornea-embedded microlens outward: the second correction region, the plano region, and the first correction region. The first correction region has the function of correcting vision loss caused by the unhealthy state of the refractive medium, the plano region does not have the function of correcting vision, and the second correction region has the function of correcting vision loss caused by refractive error. The cornea-embedded microlens is circular, wherein the second correction zone is a circle with a diameter of 1.5 mm, and the thickest part of the second correction zone is 54 μm; outside the second correction zone is an annular plano zone, the outer diameter of the plano zone is 2 mm, and the thickness of the plano zone is the same as the thickness of the edge of the second correction zone; outside the plano zone is an annular first correction zone, the outer diameter of the first correction zone is 3.8 mm (i.e., the diameter of the cornea-embedded microlens), and the thickness of the inner circumference of the first correction zone is the same as the thickness of the plano zone.

[0068] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0069] Example 6

[0070] This embodiment illustrates a cornea-embedded microlens. Based on the embodiment 1, Figure 1 For example, the cornea-embedded microlens has three areas in total, namely, "two correction areas and one plano area". The three areas are arranged in the following order, from the center of the cornea-embedded microlens to the outside: the second correction area S3, the plano area S2, and the first correction area S1. The cornea-embedded microlens is circular, wherein the second correction area S3 is a circle with a diameter of 1.5 mm, and the second correction area S3 is a concave lens with an edge thickness of 45 μm and a thickness of 0 at the optical center of the concave lens. It then expands outward from the optical center to a circular hole with a diameter of 0.4 mm. The entire circular hole is a through hole SH, that is, the thickness is 0. The thickness from the edge of the through hole SH to the second correction area gradually increases from 0. Outside the second correction area S3 is the annular plano area S2, and the outer diameter of the annular plano area S2 is 2.5 mm. The thickness of the plano zone S2 is the same as the thickness of the edge of the concave lens of the second correction zone S3; outside the plano zone S2 is the annular first correction zone S1, the cross section of the first correction zone S1 along the center direction of the annular curvature is a convex lens cross section, the convex lens of the first correction zone S1 has the same thickness as the plano zone S2 at the junction with the plano zone S2, the outer diameter of the first correction zone S1 is 4.0 mm (i.e., the diameter of the cornea-embedded microlens), and the optical center thickness of the convex lens of the first correction zone S1 is 54 μm (i.e., the thickness of the thickest part of the cornea-embedded microlens).

[0071] It should be noted that, in the three regions of the cornea-embedded microlens in this embodiment, the concave lens and the convex lens respectively include attached Figure 2 There are four situations, namely, one of the two surfaces of the concave lens (or convex lens) is a plane and the other is a concave surface (or convex surface), and also includes the situation that both surfaces are concave surfaces (or convex surfaces).

[0072] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0073] Example 7

[0074] This embodiment illustrates a cornea-embedded microlens. Based on Embodiment 1, the cornea-embedded microlens has three areas in total, namely, "two correction areas and one plano area". The three areas are arranged in the following order, from the center of the cornea-embedded microlens to the outside: the second correction area, the plano area, and the first correction area. The cornea-embedded microlens is circular, wherein the second correction zone is a circle with a diameter of 1.5 mm, and the second correction zone is a concave lens, the thickness of the edge of the concave lens is 47 μm, the thickness at the optical center of the concave lens is 0, and then it expands outward from the optical center to a circular hole with a diameter of 0.35 mm, and the entire circular hole is a through hole, that is, the thickness is 0; the thickness from the edge of the through hole to the second correction zone gradually thickens from 0; the second correction zone is outside the annular plano zone, the outer diameter of the plano zone is 2.5 mm, and the thickness of the plano zone is the same as the thickness of the edge of the concave lens of the second correction zone; the plano zone is outside the annular first correction zone, the cross section of the first correction zone along the center direction of the annular curvature is a convex lens cross section, the convex lens of the first correction zone has the same thickness as the plano zone at the junction with the plano zone, the outer diameter of the first correction zone is 4.5 mm (that is, the diameter of the cornea-embedded microlens), and the optical center thickness of the convex lens of the first correction zone is 63 μm (that is, the thickness of the thickest part of the cornea-embedded microlens). The preparation material of the cornea embedded microlens is one or more of hydroxyethyl methacrylate, 2-phenoxyethyl acrylate, ethylene glycol dimethacrylate, methyl methacrylate, polymethyl methacrylate, and styrene acrylate.

[0075] It should be noted that, in the three regions of the cornea-embedded microlens in this embodiment, the concave lens and the convex lens respectively include attached Figure 2 There are four situations, namely, one of the two surfaces of the concave lens (or convex lens) is a plane and the other is a concave surface (or convex surface), and also includes the situation that both surfaces are concave surfaces (or convex surfaces).

[0076] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0077] Example 8

[0078] This embodiment illustrates a cornea-embedded microlens. On the basis of Embodiment 1, the cornea-embedded microlens has three areas in total: "two correction areas and one plano area". The three areas are arranged in the following order, from the center of the cornea-embedded microlens to the outside: the second correction area, the plano area, and the first correction area. The cornea-embedded microlens is circular, wherein the second correction area is a circle with a diameter of 2 mm, and the second correction area is a concave lens, the thickness of the edge of the concave lens is 48 μm, the thickness at the optical center of the concave lens is 0, and then expands outward from the optical center to a circular hole with a diameter of 0.6 mm, and the entire circular hole is a through hole, that is, the thickness is 0; the thickness from the edge of the through hole to the second correction area gradually thickens from 0; the outside of the second correction area is an annular plano area, and the outside of the second correction area is an annular plano area, and the outer circle of the plano area The diameter is 2.5mm, and the thickness of the plano area is the same as the thickness of the edge of the concave lens of the second correction area; the first correction area is annular outside the plano area, and the cross section of the first correction area along the center direction of the annular curvature is a convex lens cross section, and the thickness of the convex lens of the first correction area is the same as that of the plano area at the junction with the plano area, the outer diameter of the first correction area is 3.8mm (i.e., the diameter of the cornea embedded microlens), and the optical center thickness of the convex lens of the first correction area is 62μm (i.e., the thickness of the thickest part of the cornea embedded microlens). The preparation material of the cornea embedded microlens is one or more of hydroxyethyl methacrylate, 2-phenoxyethyl acrylate, ethylene glycol dimethacrylate, methyl methacrylate, polymethyl methacrylate, and styrene acrylate, and the ultraviolet blocker of the cornea embedded microlens is azophenyl methacrylate and / or 4-propyleneoxy-2-hydroxybenzophenone.

[0079] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0080] Example 9

[0081] This embodiment illustrates a cornea-embedded microlens. On the basis of Embodiment 1, the cornea-embedded microlens has three areas in total: "two correction areas and one plano area". The three areas are arranged in the following order, from the center of the cornea-embedded microlens to the outside: the second correction area, the plano area, and the first correction area. The cornea-embedded microlens is circular, wherein the second correction area is a circle with a diameter of 1.5 mm, and the second correction area is a concave lens, the thickness of the edge of the concave lens is 34 μm, the thickness at the optical center of the concave lens is 0, and then expands outward from the optical center to a circular hole with a diameter of 0.3 mm, and the entire circular hole is a through hole, that is, the thickness is 0; the thickness from the edge of the through hole to the second correction area gradually thickens from 0; the outside of the second correction area is an annular plano area, and the outside of the second correction area is an annular plano area, and the outside of the plano area The circular diameter is 2.0mm, the thickness of the plano area is the same as the thickness of the edge of the concave lens of the second correction area; the first correction area is annular outside the plano area, the cross section of the first correction area along the center direction of the circular curvature is a convex lens cross section, the convex lens of the first correction area is the same thickness as the plano area at the junction with the plano area, the outer diameter of the first correction area is 3.3mm (i.e. the diameter of the cornea embedded microlens), and the optical center thickness of the convex lens of the first correction area is 52μm (i.e. the thickness of the thickest part of the cornea embedded microlens). The preparation material of the cornea embedded microlens is a combination of hydroxyethyl methacrylate and methyl methacrylate, and the ultraviolet blocker of the cornea embedded microlens is 4-propyleneoxy-2-hydroxybenzophenone.

[0082] It should be noted that, among the three regions of the cornea-embedded microlens in this embodiment, the concave lens in the second correction region and the convex lens in the first correction region respectively include attached Figure 2 There are four situations, namely, one of the two surfaces of the concave lens (or convex lens) is a plane and the other is a concave surface (or convex surface), and also includes the situation that both surfaces are concave surfaces (or convex surfaces).

[0083] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts, thereby obtaining a corneal embedded microlens with vision correction effect.

[0084] Example 10

[0085] This embodiment illustrates a cornea-embedded microlens. On the basis of Embodiment 1, the cornea-embedded microlens has three areas in total: "two correction areas and one plano area". The three areas are arranged in the following order, from the center of the cornea-embedded microlens to the outside: the second correction area, the plano area, and the first correction area. The cornea-embedded microlens is circular, wherein the second correction area is a circle with a diameter of 1.6 mm, and the second correction area is a concave lens, the thickness of the edge of the concave lens is 48 μm, the thickness at the optical center of the concave lens is 0, and then expands outward from the optical center to a circular hole with a diameter of 0.2 mm, and the entire circular hole is a through hole, that is, the thickness is 0; the thickness from the edge of the through hole to the second correction area gradually thickens from 0; the outside of the second correction area is an annular plano area, and the outside of the second correction area is an annular plano area, and the outer circle of the plano area The diameter is 2.2mm, and the thickness of the plano area is the same as the thickness of the edge of the concave lens of the second correction area; the first correction area is annular outside the plano area, and the cross section of the first correction area along the center of the annular curvature is a convex lens cross section, and the convex lens of the first correction area is the same thickness as the plano area at the junction with the plano area, the outer diameter of the first correction area is 3.4mm (i.e., the diameter of the cornea embedded microlens), and the optical center thickness of the convex lens of the first correction area is 67μm (i.e., the thickness of the thickest part of the cornea embedded microlens). The preparation material of the cornea embedded microlens is a combination of hydroxyethyl methacrylate and methyl methacrylate, and the mass ratio of the two is 3:1, and 4-propyleneoxy-2-hydroxybenzophenone is added to the preparation material as a UV blocker.

[0086] It should be noted that, among the three regions of the cornea-embedded microlens in this embodiment, the concave lens in the second correction region and the convex lens in the first correction region respectively include attached Figure 2 There are four situations, namely, one of the two surfaces of the concave lens (or convex lens) is a plane and the other is a concave surface (or convex surface), and also includes the situation that both surfaces are concave surfaces (or convex surfaces).

[0087] Embodiment 11

[0088] This embodiment illustrates a cornea-embedded microlens. On the basis of Embodiment 1, the preparation material of the cornea-embedded microlens is one or more of hydroxyethyl methacrylate, 2-phenoxyethyl acrylate, ethylene glycol dimethacrylate, methyl methacrylate, polymethyl methacrylate, styrene acrylate, and hydroxyethyl methacrylate, and the preparation material is added with ultraviolet blockers azophenyl methacrylate and / or 4-propyleneoxy-2-hydroxybenzophenone. The cornea-embedded microlens has three regions, namely, "two correction regions and one plano region", and the arrangement order of the three regions is, from the center of the cornea-embedded microlens to the outside, the second correction region, the plano region, and the first correction region. The cornea-embedded microlens is circular, wherein the second correction zone is a circle with a diameter of 1.4 mm, and the second correction zone is a concave lens, the edge thickness of the concave lens is 37 μm, the thickness at the optical center of the concave lens is 0, and then it expands outward from the optical center to a circular hole with a diameter of 0.3 mm, and the entire circular hole is a through hole, that is, the thickness is 0; the thickness from the edge of the through hole to the second correction zone gradually thickens from 0; the outside of the second correction zone is an annular plano area, and the outside of the plano area is an annular plano area. The circular diameter is 2.0mm, and the thickness of the plano area is the same as the thickness of the edge of the concave lens of the second correction area; the first correction area is annular outside the plano area, and the cross section of the first correction area along the center of the circular curvature is a convex lens cross section. The convex lens of the first correction area is the same thickness as the plano area at the junction with the plano area. The outer diameter of the first correction area is 3.5mm (i.e., the diameter of the cornea-embedded microlens), and the optical center thickness of the convex lens of the first correction area is 55μm (i.e., the thickness of the thickest part of the cornea-embedded microlens). The preparation material of the cornea-embedded microlens is a composition of hydroxyethyl methacrylate and methyl methacrylate, and the mass ratio of the two is 3:1. The ultraviolet blocker of the cornea-embedded microlens is 4-propyleneoxy-2-hydroxybenzophenone.

[0089] The cornea embedded microlens prepared in this embodiment is as shown in the attached Figure 2 middle Figure 2 -B, please see the attached diagram for a simulated diagram of the full-definition visual imaging effect. Figure 5 .

[0090] Example 12

[0091] This embodiment illustrates a method for preparing a cornea-embedded microlens, which is specifically as follows: step A. weighing 75 grams of hydroxyethyl methacrylate, 5 grams of 2-phenoxyethyl acrylate, and 22 grams of ethylene glycol dimethacrylate respectively; step B. weighing 0.9 grams of 4-propyleneoxy-2-hydroxybenzophenone and adding it to the solution prepared in step A; stirring evenly, and pouring it into a mold; step C. drying at 80-120° C. for 4-8 hours to prepare a buckle material; step D. cutting and polishing the buckle material using a machine tool to obtain a circular cornea-embedded microlens with a diameter of 4.2 mm. The second correction zone of the cornea embedded microlens is a circle with a diameter of 1.6 mm, and the second correction zone is a concave lens, and the edge thickness of the concave lens is 47 μm; the optical center of the concave lens is a through hole, and since the mold has a cylinder with a diameter of 0.5 mm, the cornea embedded microlens prepared in this embodiment has a circular through hole with the same diameter after molding; the second correction zone is an annular plano zone, the outer diameter of the plano zone is 2.4 mm, the inner circle of the annular plano zone is the circumferential edge of the second correction zone, and the thickness of the plano zone is the same as the thickness of the edge of the concave lens of the second correction zone; the plano zone is an annular first correction zone, the cross section of the first correction zone along the center direction of the annular curvature is a convex lens cross section, the thickness of the first correction zone convex lens and the plano zone at the junction is the same as the thickness of the plano zone, the outer diameter of the first correction zone is the diameter of the cornea embedded microlens, and the optical center thickness of the convex lens of the first correction zone is 57 μm (i.e., the thickness of the thickest part of the cornea embedded microlens). The prepared cornea-embedded microlens is placed in a physiological saline solution containing 3 mg / ml tobramycin for hydration, and the cornea-embedded microlens is placed in the hydration solution; step E. packaging, storage, and transportation, during which the cornea is placed in a solution containing all the components of the hydration solution. Before clinical use, the cornea is taken out of the package and used directly.

[0092] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts. For example, the size and surface smoothness of the corneal embedded microlens after molding can be changed by adjusting the diameter, thickness, diameter of the cylinder in the mold, smoothness of the mold surface, etc., so as to obtain a corneal embedded microlens with vision correction effect suitable for different patients.

[0093] Embodiment 13

[0094] This embodiment illustrates a method for preparing a cornea-embedded microlens, which is specifically as follows: step A. weighing 60 grams of hydroxyethyl methacrylate, 15 grams of 2-phenoxyethyl acrylate, and 5 grams of ethylene glycol dimethacrylate respectively; step B. weighing 0.35 grams of azophenyl methacrylate and 0.35 grams of 4-propyleneoxy-2-hydroxybenzophenone and adding them to the mixed solution prepared in step A; stirring evenly and pouring into a mold; step C. drying at 80-120° C. for 4-8 hours to prepare a buckle material; step D. cutting and polishing the buckle material using a machine tool to obtain a circular cornea-embedded microlens with a diameter of 3.8 mm. The second correction zone of the cornea embedded microlens is a circle with a diameter of 1.4 mm, and the second correction zone is a concave lens, and the thickness of the edge of the concave lens is 44 μm; the optical center of the concave lens is a through hole, and since the mold has a cylinder with a diameter of 0.3 mm, the cornea embedded microlens prepared in this embodiment has a circular through hole with the same diameter after molding; the second correction zone is an annular plano zone, the outer diameter of the plano zone is 2.4 mm, the inner circle of the annular plano zone is the circumferential edge of the second correction zone, and the thickness of the plano zone is the same as the thickness of the edge of the concave lens of the second correction zone; the plano zone is an annular first correction zone, the cross section of the first correction zone along the center direction of the annular curvature is a convex lens cross section, the thickness of the convex lens of the first correction zone at the junction with the plano zone is the same as the thickness of the plano zone, the outer diameter of the first correction zone is the diameter of the cornea embedded microlens, and the optical center thickness of the convex lens of the first correction zone is 54 μm (i.e., the thickness of the thickest part of the cornea embedded microlens). The prepared cornea-embedded microlens is placed in a physiological saline solution containing 3 mg / ml tobramycin for hydration, and the cornea-embedded microlens is placed in the hydration solution; step E. packaging, storage, and transportation, during which the cornea is placed in a solution containing all the components of the hydration solution. Before clinical use, the cornea is taken out of the package and used directly.

[0095] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts. For example, the size and surface smoothness of the corneal embedded microlens after molding can be changed by adjusting the diameter, thickness, diameter of the cylinder in the mold, smoothness of the mold surface, etc., so as to obtain a corneal embedded microlens with vision correction effect suitable for different patients.

[0096] Embodiment 14

[0097] This embodiment illustrates a method for preparing a cornea-embedded microlens, which is specifically as follows: step A. weighing 90 grams of hydroxyethyl methacrylate and 30 grams of methyl methacrylate respectively; step B. weighing 1.2 grams of 4-propyleneoxy-2-hydroxybenzophenone and adding it to the mixed solution prepared in step A; stirring evenly and pouring it into a mold; step C. drying at 80-120° C. for 4-8 hours to prepare a buckle material; step D. cutting and polishing the buckle material using a machine tool to obtain a circular cornea-embedded microlens with a diameter of 3.5 mm. The second correction zone of the cornea embedded microlens is a circle with a diameter of 1.6 mm, and the second correction zone is a concave lens, and the edge thickness of the concave lens is 36 μm; the optical center of the concave lens is a through hole, and since the mold has a cylinder with a diameter of 0.5 mm, the cornea embedded microlens prepared in this embodiment has a circular through hole with the same diameter after molding; the second correction zone is an annular plano zone, the outer diameter of the plano zone is 2.1 mm, the inner circle of the annular plano zone is the circumferential edge of the second correction zone, and the thickness of the plano zone is the same as the thickness of the edge of the concave lens of the second correction zone; the plano zone is an annular first correction zone, the cross section of the first correction zone along the center direction of the annular curvature is a convex lens cross section, the thickness of the first correction zone convex lens and the plano zone at the junction is the same as the thickness of the plano zone, the outer diameter of the first correction zone is the diameter of the cornea embedded microlens, and the optical center thickness of the convex lens of the first correction zone is 56 μm (i.e., the thickness of the thickest part of the cornea embedded microlens). The prepared cornea-embedded microlens is placed in a physiological saline solution containing 3 mg / ml tobramycin for hydration, and the cornea-embedded microlens is placed in the hydration solution; step E. packaging, storage, and transportation, during which the cornea is placed in a solution containing all the components of the hydration solution. Before clinical use, the cornea is taken out of the package and used directly.

[0098] For materials, conditions and parameters not described in this embodiment, those skilled in the art can select reagents, materials, parameters and specific settings for implementation with creative efforts. For example, the size and surface smoothness of the corneal embedded microlens after molding can be changed by adjusting the diameter, thickness, diameter of the cylinder in the mold, smoothness of the mold surface, etc., so as to obtain a corneal embedded microlens with vision correction effect suitable for different patients.

[0099] Embodiment 15

[0100] This example illustrates the incidence of clouding or turbidity after the cornea-embedded microlens prepared by the preparation method provided in Example 14 is implanted into the cornea of ​​an animal. The details are as follows:

[0101] 1. Test materials and equipment:

[0102] 1. 12 experimental rabbits;

[0103] 2. Test materials: 6 cornea-embedded microlenses prepared by the preparation method of Example 14;

[0104] 3. Comparative materials: 6 cornea-embedded microlenses with the same size as the cornea-embedded microlenses prepared in Example 14 but without central holes;

[0105] 4. Normal saline, lidocaine hydrochloride, etc.

[0106] 5. Main equipment: surgical microscope, face opener, ophthalmic separator, implanter, sleeve, surgical instruments, slit lamp, ophthalmic B-ultrasound, etc.

[0107] 2. Test process

[0108] 1. Experimental groups: 6 rabbits in the control group were numbered and implanted with a comparison material (a corneal embedded microlens without a central hole); 6 rabbits in the experimental group were numbered and implanted with a test material (a corneal embedded microlens with a central hole prepared by the preparation method of Example 14).

[0109] 2. Experimental process: The rabbit's eye was cleaned before surgery, and then the corneal stroma pocket was prepared with a scalpel. After the pocket was separated with a separator, the microlens was pushed into the pocket with a surgical implanter. After surgery, the tobramycin dexamethasone eye drops were administered according to the instructions. The rabbit was observed for 12 months after surgery.

[0110] 3. Scoring Criteria

[0111]

[0112] 4. Test results

[0113] The scores were recorded at 3 months, 6 months, and 12 months after surgery as follows:

[0114]

[0115] V. Test Conclusion

[0116] The test results showed that the test rabbits implanted with the corneal embedded microlens with a central hole were completely transparent for 12 consecutive months, and no clouding or corneal opacity occurred. The control group had 3 cases of corneal opacity and clouding at 6 months, and there was a trend of further aggravation at 12 months. The test conclusion is that the corneal embedded microlens with a central hole prepared in Example 14 did not show clouding or corneal opacity for 12 consecutive months.

[0117] Example 16

[0118] This embodiment illustrates a method for preparing a corneal embedded microlens with ultraviolet blocking function, and evaluates the preparation material and preparation method of the corneal embedded microlens through aging, hydration, transparency, biocompatibility, and sustained antibiotic release tests. The details are as follows:

[0119] Experimental group 1: The preparation material is a composition of "2-phenoxyethyl acrylate, ethylene glycol dimethacrylate, 4-propyleneoxy-2-hydroxybenzophenone";

[0120] Experimental group 2: The preparation material is a composition of "hydroxyethyl methacrylate, methyl methacrylate, 4-propyleneoxy-2-hydroxybenzophenone";

[0121] Experimental group 3: The preparation material is a composition of "methyl methacrylate, styrene acrylate, 4-propyleneoxy-2-hydroxybenzophenone";

[0122] Experimental group 4: The preparation material is a composition of "polymethyl methacrylate, ethylene glycol dimethacrylate, and azophenyl methacrylate";

[0123] Experimental group 5: The preparation material is a composition of "styrene acrylate, 2-phenoxyethyl acrylate, and azophenyl methacrylate";

[0124] According to the preparation method provided in Example 14, the preparation materials and ultraviolet blockers of the corneal embedded microlens were replaced with the corresponding materials of the above test groups, and the materials and parameters not recorded in each test group were all as recorded in Example 14, so as to prepare the corneal embedded microlens with the corresponding test group number.

[0125] 1. Test methods

[0126] 1. Aging test

[0127] The corneal embedded microlenses were subjected to accelerated aging at 60°C. Samples were taken at 1, 3, 5, 8 and 12 months, and the content of UV blockers was measured by spectral analysis to evaluate the aging of the microlenses.

[0128] 2. Softness test

[0129] Test the softness and make a comparison.

[0130] 3. Transparency, biocompatibility and sustained release of antibiotics

[0131] The antibiotic release duration and transparency of the microlens were investigated.

[0132] 3.1 Test materials:

[0133] 1) 40 experimental rabbits;

[0134] 2) Normal saline, lidocaine hydrochloride, surgical instruments, slit lamp, ophthalmic B-ultrasound, etc.

[0135] 3) Main equipment: surgical microscope, face opener, ophthalmic separator, implanter, sleeve, etc.

[0136] 3.2 Test process:

[0137] Before surgery, the rabbit's eye was cleaned, and then a corneal stroma pocket was prepared with a scalpel. After the pocket was separated with a separator, the microlens was pushed into the pocket with a surgical implanter and centered. Dexamethasone eye drops were applied after surgery.

[0138] Continuous observation was performed after surgery, and antibiotic test results were recorded at 8-12-18-24 hours after surgery, and finally transparency was recorded and observed at 12 months after surgery.

[0139] 3.3 Transparency Rating Criteria

[0140]

[0141] 2. Test results

[0142] 1. Record of microlens aging

[0143]

[0144] From the test results, it can be seen that the above material combinations are stable and no premature aging of the materials occurs.

[0145] 2. Softness test record

[0146] serial number Softness ranking Experimental Group 1 2 Experimental Group 2 1 Experimental Group 3 2 Experimental Group 4 2 Experimental Group 5 3

[0147] From the test results, it can be seen that the material softness test group 2 is softer than the other groups.

[0148] 3. Transparency and antibiotic release records

[0149] (1) The corneal transparency scores at 12 months after surgery were as follows:

[0150] Group Experimental Group 1 Experimental Group 2 Experimental Group 3 Experimental Group 4 Experimental Group 5 transparency 0 0 0 0 0

[0151] From the results of this experiment, it can be seen that the corneal transparency of each group was basically the same 12 months after surgery.

[0152] (2) Antibiotic test results:

[0153]

[0154] From the results of this experiment, we can see that tobramycin was detected in all experimental groups at 8-12 hours, tobramycin was not detected in experimental group 5 from 12 hours after surgery but was detected in other groups, and tobramycin was still detected in experimental group 2 at 18 hours after surgery but was not detected at 24 hours after surgery.

[0155] 3. Test Conclusion

[0156] The test results of this group show that when the preparation material is a copolymer of one or more of 2-phenoxyethyl acrylate, ethylene glycol dimethacrylate, methyl methacrylate, polymethyl methacrylate, and styrene acrylate, the material process is stable, the fusion with the UV blocker is relatively stable, and there is no premature aging phenomenon, and the biocompatibility is good. The results of the softness and antibiotic release tests show that when the preparation material is selected from test group 2, namely "hydroxyethyl methacrylate, methyl methacrylate, 4-propyleneoxy-2-hydroxybenzophenone", the softness of the microlens is better, and the tobramycin release time can exceed 18 hours. Therefore, the material selected in test group 2 is better.

[0157] Embodiment 17

[0158] This embodiment illustrates several components of the hydration solution and / or preservation solution in a method for preparing a corneal embedded microlens with antibiotics, and selects a better hydration solution through comparison. The details are as follows:

[0159] The components of the hydration solution and / or preservation solution exemplified in this embodiment were prepared and tested according to the following test groups.

[0160] Test group 1: containing only tobramycin;

[0161] Experimental group 2: containing tobramycin, bFGF, and VB2;

[0162] Test group 3: without any additives (blank control).

[0163] According to the components of the hydration solution shown above, the cornea-embedded microlenses (9 in total) prepared by the preparation method provided in Example 14 were implanted on the cornea of ​​animals to evaluate the postoperative recovery effect. The details are as follows:

[0164] The components in the hydration solution in the preparation method provided in Example 14 were replaced with the corresponding components of the above test groups, and the materials and parameters not recorded in each test group were prepared according to the description in Example 14 to prepare the corneal embedded microlenses with the corresponding test group numbers.

[0165] 1. Test materials and equipment

[0166] 1. 9 experimental rabbits;

[0167] 2. Reagents: physiological saline, lidocaine hydrochloride, etc.

[0168] 3. Main equipment: surgical microscope, face opener, ophthalmic separator, implanter, ophthalmic B-ultrasound, slit lamp, etc.

[0169] 2. Test process

[0170] The rabbit's eye was cleaned before surgery, and then a scalpel was used to prepare the corneal stroma pocket. After the pocket was separated with a separator, the microlens was pushed into the pocket with a surgical implant. After surgery, the tobramycin dexamethasone eye drops were administered according to the instructions. The rabbit was observed for 3 months after surgery. Histological sections were taken at 3 months after surgery to observe the nerve growth.

[0171] 3. Corneal transparency scoring criteria:

[0172]

[0173] 4. Test results

[0174] 1. Corneal transparency observation and record

[0175]

[0176] The results showed that the rabbit eyes of each test group remained transparent after surgery, indicating that the corresponding ingredients added to test groups 1-5 did not affect the transparency of the rabbit eyes after surgery.

[0177] 2. Observation and recording of nerve fiber growth

[0178] The slices showed that at 1 month, the number of nerves with distortion and increased reflectivity in the plexus images decreased slightly, and at 3 months after surgery, this phenomenon decreased, and the plexus tended to the preoperative nerve morphology characteristics. The nerve recovery status of experimental group 6 was slightly lower than that of the other experimental groups. This shows that the microlens with modified surface has a better postoperative effect.

[0179] It should be noted that the above is only a preferred embodiment of the specific implementation of the present invention, and is not a limitation of the technical solution protected by the present invention. Any technician familiar with the technical field, within the scope of the technical solution disclosed by the present invention, who makes equivalent substitutions or changes to the inventive concept of the technical solution of the present invention, should be covered by the protection scope of the present invention.

Claims

1. A cornea-embedded microlens, wherein the microlens is circular and comprises two regions, characterized in that: The two areas are respectively a first correction area and a plano area, the plano area is surrounded by the first correction area, the first correction area is concentric with the plano area, the first correction area has the function of correcting vision, the refractive power of the plano area is 0D, and the plano area has a through hole; the cornea-embedded microlens has the function of blocking the transmission of ultraviolet rays.

2. The cornea-embedded microlens according to claim 1, characterized in that: The plano area includes a second correction area, the second correction area is circular and surrounded by the plano area, and the through hole is located in the second correction area.

3. The cornea-embedded microlens according to claim 2, characterized in that: The first correction zone has a function of correcting vision loss caused by an unhealthy state of the refractive medium, and the second correction zone has a function of correcting vision loss caused by refractive error.

4. The cornea-embedded microlens according to claim 2, characterized in that: The number of the through hole is 1, the through hole is circular and concentric with the second correction area, and the second correction area is concentric with the flat light area.

5. The cornea-embedded microlens according to claim 3, characterized in that: The cross section of the first correcting zone along the center direction of the annular curvature is a convex lens cross section, and / or the cross section of the second correcting zone along the center direction of the circular curvature is a concave lens cross section.

6. The cornea-embedded microlens according to claim 5, characterized in that: The optical center of the concave lens is a through hole, and the diameter of the through hole is 0.01-0.6 mm.

7. The cornea-embedded microlens according to claim 1, characterized in that: The diameter of the microlens is 2.5-5.5 mm; the thickness of the microlens is 25-63 μm.

8. The method for preparing a cornea-embedded microlens according to any one of claims 1 to 7, characterized in that: The following steps are involved: Step A. weighing one or more of hydroxyethyl methacrylate, 2-phenoxyethyl acrylate, ethylene glycol dimethacrylate, methyl methacrylate, polymethyl methacrylate, styrene acrylate, and hydroxyethyl methacrylate to prepare a mixed solution; Step B. Weighing azophenyl methacrylate and / or 4-propyleneoxy-2-hydroxybenzophenone, adding them to the mixed solution prepared in step A; stirring them evenly and adding them to a mold; the mold has a cylindrical shape so that the solution has the through hole after being molded in the mold; Step C. drying at 80-120° C. for 4-8 hours to prepare a buckle material; Step D: cutting, polishing and hydrating the buckle material to prepare a cornea-embedded microlens; The hydration solution used in the hydration is a physiological saline solution containing antibiotics.

9. The preparation method according to claim 8, characterized in that: The cylinder is perpendicular to the mold surface, and the connection part between the cylinder and the mold has a circular curvature on a section along the axis of the cylinder, so that the cross-section of the second correction zone of the mixed liquid after being formed in the mold along the center of the circular curvature is a concave lens cross-section; the outer ring of the mold surrounding the second correction zone is a plane, so that the mixed liquid has a flat light zone after being formed in the mold; the outer ring of the mold surrounding the flat light zone has a circular curvature on a section along the axis of the cylinder, so that the cross-section of the first correction zone of the mixed liquid after being formed in the mold along the center of the circular curvature is a convex lens cross-section.

10. Use of the cornea-embedded microlens according to any one of claims 1 to 7 in a product for correcting vision loss caused by an unhealthy state of a refractive medium, and / or in a product for correcting vision loss caused by ametropia.

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