Personalized corneal contact lens microneedle device for treating corneal dilation diseases

Abstract

The invention provides a personalized corneal contact lens microneedle device for treating corneal dilation diseases, which comprises a fixing device and a drug delivery device, the drug delivery device comprises a drug delivery main body and a drug delivery microneedle arranged on the drug delivery main body; the fixing device surrounds the periphery of the drug delivery main body and is concentric with the drug delivery main body and embedded with the drug delivery main body; wherein the fixing device fixes the whole corneal contact lens microneedle device on the surface of a cornea through the fixing microneedle, a biomechanical effect is generated around the cornea to control the corneal curvature progress, and meanwhile, the medicine delivery microneedle is fixed in the center of the cornea; the drug delivery microneedle is used for penetrating through the cornea epithelium to reach the cornea stroma layer, so that the drug on the drug delivery main body permeates into the cornea stroma layer, and finally, the thickness and hardness of the cornea stroma layer are increased in combination with ultraviolet irradiation, and the disease progress is controlled. The treatment mode is safe and efficient, and nano-drugs are not needed.

Description

Technical Field

[0001] The invention belongs to the medical field, and in particular relates to a personalized corneal contact lens microneedle device for treating corneal ectasia diseases. Background Art

[0002] Corneal ectatic diseases refer to a class of ophthalmic diseases in which the morphology and function of the cornea change, usually manifested as convex or irregular expansion of the cornea. Corneal ectatic diseases include the following types: ① Keratoconus is an eye disease characterized by the expansion and thinning of the central or paracentral cornea and its cone-shaped protrusion forward. The disease often leads to highly irregular astigmatism, which seriously affects the quality of vision. In the late stage, patients may experience significant vision loss or even blindness. ② Abnormal corneal topography after corneal refractive surgery is a complication related to refractive surgery, which manifests as abnormal expansion and irregular shape of the cornea. ③ Corneal degeneration is a relatively rare hereditary disease in which the patient's cornea is uniformly expanded and weak, often accompanied by deformation of the eyeball. ④ Flat cornea is a relatively rare corneal morphological abnormality in which the patient's corneal curvature is relatively flat, which may cause mild myopia or vision problems. The disease is characterized by the lack of normal curvature on the anterior surface of the cornea, usually without significant visual impairment. ⑤ Posterior corneal ectasia is an expansion of the inner layer of the cornea, which is mainly manifested as a protrusion of the posterior surface of the cornea. It is usually hidden and the early symptoms are not obvious. ⑥ Corneal ectasia caused by other reasons.

[0003] The treatment methods for these corneal ectasia diseases vary depending on the condition, and usually include wearing frame glasses, hard gas-permeable corneal contact lenses, corneal collagen cross-linking therapy, corneal transplantation surgery, etc. Early effective intervention therapy can slow down the progression of the disease and reduce the burden of the disease. However, the current clinical use of non-surgical intervention therapy to delay or prevent the progression of corneal ectasia is insufficient. For patients with rapid disease progression, corneal collagen cross-linking surgery or even corneal transplantation surgery is still required. In the early stages of corneal ectasia or keratoconus (the thinnest part of the cornea is greater than 400 μm), corneal collagen cross-linking can slow down the progression of the disease to a certain extent. Due to the barrier effect of the corneal epithelium on macromolecules such as riboflavin, the corneal epithelium needs to be scraped off during the operation so that riboflavin can effectively penetrate into the corneal stroma layer. Combined with ultraviolet light irradiation, the corneal stromal cells and riboflavin produce collagen cross-linking reaction, which improves the mechanical strength of the corneal tissue and resists corneal ectasia. When the disease progresses further or the cornea becomes thinner and the thickness is less than 400 μm, corneal transplantation surgery is the main treatment method.

[0004] The disadvantages of current technology are: Corneal collagen cross-linking surgery: (1) The corneal epithelium must be scraped to allow riboflavin to reach the corneal stroma where it needs to act. The corneal epithelium is rich in nerves, and scraping will cause irritation and pain, and there is a risk of corneal infection and even ulcers. Especially for patients with diabetes or long-term use of hormone drugs, corneal epithelial defects are difficult to recover and may even be delayed and unhealed; (2) The scope of corneal collagen cross-linking depends on the doctor's experience, and it is impossible to accurately and objectively perform collagen cross-linking on the thinning area of ​​the cornea. Corneal transplant surgery: Donor cornea resources are scarce, and there is a risk of immune rejection and infection after corneal transplantation.

[0005] In terms of research progress at home and abroad, some scholars have proposed contact lens-assisted corneal cross-linking. This technology places a contact lens soaked with riboflavin on the surface of the patient's cornea to promote the penetration of riboflavin into the corneal stroma. However, the hydrophilic contact lens used in this technology has a low drug loading, which makes it difficult to meet the drug concentration required for effective cross-linking; and the corneal epithelium still needs to be scraped off, which cannot solve the challenges of existing technologies. In recent years, many studies have actively explored non-invasive means of riboflavin combined with ultraviolet light irradiation corneal cross-linking, such as riboflavin composite nanomaterials for transepithelial drug delivery, which can effectively deliver riboflavin to the corneal stroma without removing the corneal epithelium. This type of design avoids corneal epithelial damage and maintains the effective concentration of riboflavin in the stroma by optimizing the drug delivery system. However, the safety of nanodrugs after entering the eye needs to be further studied, and their distribution, metabolism and absorption pathways in the eye have not yet been clarified. A new, safe and efficient treatment method is urgently needed. Summary of the invention

[0006] In view of the deficiencies in the above-mentioned prior art, the present invention provides a personalized corneal contact lens microneedle device for treating corneal ectatic diseases. The corneal contact lens microneedle device of the present invention not only avoids corneal epithelial damage, but also can deliver drugs of sufficient concentration to the corneal stroma, and does not require the use of nanomedicines, and the treatment effect is safe and efficient.

[0007] The object of the present invention is to provide a personalized corneal contact lens microneedle device for treating corneal ectasia diseases, comprising:

[0008] A drug delivery device, comprising a drug delivery body and a drug delivery microneedle disposed on the drug delivery body;

[0009] A fixing device, surrounding the outer periphery of the drug delivery body and being concentric with and embedded in the drug delivery body;

[0010] Among them, the fixing device is used to be fixed on the corneal surface to fix the drug delivery body on the thinned area of ​​the cornea, and the drug delivery microneedle is used to penetrate the corneal epithelium to reach the corneal stroma layer to penetrate the drug on the drug delivery body into the corneal stroma layer, and after combined with ultraviolet light irradiation, the therapeutic effect of increasing the thickness and hardness of the cornea in the thinned area is achieved.

[0011] In some embodiments of the present invention, the fixing device includes a peripheral area, and the peripheral area is used to fit on the corneal surface to fix the personalized corneal contact lens microneedle device on the corneal surface.

[0012] In some embodiments of the present invention, the fixing device also includes a fixing microneedle arranged on the peripheral area, and the fixing microneedle is used to penetrate the corneal epithelium and the superficial stroma to fix the corneal contact lens device, so that the fixing area is tightly fitted to the corneal surface around the corneal thinning area, and the fixing microneedle and the fixing area control the corneal curvature through biomechanical effects at the periphery of the cornea.

[0013] In some embodiments of the present invention, the shape of the fixed microneedle includes but is not limited to "pine tree shape" or "arrow shape".

[0014] In some embodiments of the present invention, the peripheral zone includes a first rear surface facing the corneal surface and a front surface facing away from the corneal surface, the first rear surface is a plane, and the front surface is a curved surface.

[0015] In some embodiments of the present invention, the peripheral area includes a connection area, a fixed area, and an edge area which are arranged in sequence from close to the drug delivery body to away from the drug delivery body, the connection area is connected to the drug delivery body, and the fixed microneedle is arranged in the fixed area.

[0016] In some embodiments of the present invention, the fixing area further includes a second rear surface facing the corneal surface, the fixing microneedle is arranged on the second rear surface, and the angle between the tangent line of the contact point of the second rear surface and the needle body of the fixing microneedle is ≤90. o .

[0017] In some embodiments of the present invention, the drug delivery body is provided with a first micropore, and the drug delivery microneedle is provided with a second micropore, a liquid conduction channel and a third micropore which are connected in sequence in the direction from the needle tail to the needle head. The needle tail of the drug delivery microneedle is connected to the drug delivery body so that the second micropore is connected to the first micropore, and when the needle head of the drug delivery body penetrates into the corneal stroma layer, the third micropore is used to penetrate the drug into the corneal stroma layer.

[0018] In some embodiments of the present invention, a first connecting portion is provided on the drug delivery body, and a second connecting portion is provided on the fixing device, and the second connecting portion is connected to the first connecting portion to connect the fixing device to the drug delivery device.

[0019] In some embodiments of the present invention, the material of the fixing device includes but is not limited to at least one of fluorosilicone-based polymers, polymethyl methacrylate, silicone hydrogel, and polyurethane.

[0020] In some embodiments of the present invention, the material of the drug delivery device includes but is not limited to at least one of polylactic acid, polyhydroxyalkanoate, and polylactic acid-glycolic acid copolymer.

[0021] Another object of the present invention is to provide a method for preparing the personalized corneal contact lens microneedle device for treating corneal ectasia diseases, comprising the following steps:

[0022] S1. Obtain different corneal morphological parameters for each person, and according to the corneal morphological parameters, make a personalized drug delivery device mold through 3D printing for the range of corneal thinning area;

[0023] S2. The material for preparing the drug delivery device is melted, heated to 150°C-160°C, poured into a drug delivery device mold, bubbles are removed, cooled and solidified, and the drug delivery device is obtained after demolding;

[0024] S3. Print the fixture using 3D printing technology, perform light curing, and clean the fixture to obtain the fixture;

[0025] S4. The drug delivery device and the fixing device are tightly connected and cleaned and disinfected to obtain a corneal contact lens microneedle device for treating corneal ectasia diseases.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] (1) The fixing device of the present invention fixes the entire corneal contact lens microneedle device on the corneal surface by fixing the microneedle; generates biomechanical effects on the periphery of the cornea to control the progression of corneal curvature, and fixes the drug delivery microneedle in the center of the cornea through the mosaic device; the drug delivery microneedle is used to penetrate the corneal epithelium to reach the corneal stroma, so as to infiltrate the drug on the drug delivery body into the corneal stroma, and finally combines with ultraviolet light irradiation to increase the thickness and hardness of the corneal stroma to control the progression of the disease.

[0028] (2) The corneal contact lens microneedle device of the present invention can combine biomechanical effects and drug solidification effects to control corneal thinning and dilation and curvature progression. The minimally invasive and degradable design of the microneedle avoids corneal epithelial damage caused by traditional treatment methods, and the treatment effect is more efficient and safe.

[0029] (3) The present invention can combine the biomechanical effect of the fixed microneedles of the fixing device and the drug treatment of the drug delivery device, achieving the effect of 1+1>2.

[0030] (4) The present invention can customize personalized corneal contact lens microneedle devices according to the corneal morphological characteristics of different patients, avoiding the traditional one-size-fits-all approach. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0032] Figure 1 A schematic diagram of the structure of a personalized corneal contact lens microneedle device for the treatment of corneal ectasia;

[0033] Figure 2 A schematic diagram of the partially enlarged structure of a drug delivery microneedle;

[0034] Figure 3 It is a schematic diagram of the structure of two different connection modes between the drug delivery device and the fixing device;

[0035] Figure 4 Microscopic morphology characterization and penetration ability testing of microneedles for drug delivery;

[0036] Figure 5 The dissolution of drug delivery microneedles within 30 minutes after contact with artificial tears;

[0037] Figure 6 To test the penetration ability of drug delivery microneedles in corneal tissue;

[0038] Figure 7 To investigate the in vivo biological safety and efficacy of a personalized contact lens microneedle device for the treatment of corneal ectasia;

[0039] 1. Fixing device; 2. Drug delivery device; 3. Edge area; 4. Fixing area; 5. Connection between the fixing device and the drug delivery device; 6. Fixing microneedle; 7. Peripheral area; 8. Drug delivery microneedle; 9. Micropore; 10. Drug delivery body. DETAILED DESCRIPTION

[0040] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0041] In the present invention, the directions or positional relationships indicated by the terms "upper", "lower", "left", "right", "front", "back", "top", "bottom", "inner", "outer", "middle", "vertical", "horizontal", "lateral", "longitudinal" and the like are based on the directions or positional relationships shown in the drawings. These terms are mainly used to better describe the present invention and its embodiments, and are not used to limit the indicated devices, elements or components to have a specific direction, or to be constructed and operated in a specific direction.

[0042] In addition, some of the above terms may be used to express other meanings in addition to indicating orientation or positional relationship. For example, the term "on" may also be used to express a certain dependency or connection relationship in some cases. For those skilled in the art, the specific meanings of these terms in the present invention can be understood according to specific circumstances.

[0043] In addition, the terms "installed", "set", "provided with", "connected", and "connected" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral structure; it can be a mechanical connection, or an electrical connection; it can be a direct connection, or an indirect connection through an intermediate medium, or it can be an internal connection between two devices, elements, or components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0044] In addition, the terms "first", "second", etc. are mainly used to distinguish different devices, elements or components (the specific types and structures may be the same or different), and are not used to indicate or imply the relative importance and quantity of the indicated devices, elements or components. Unless otherwise specified, "plurality" means two or more.

[0045] The technical solution of the present invention will be further described below in conjunction with embodiments and drawings.

[0046] See also Figures 1 to 3To achieve the above-mentioned purpose, the first aspect of the present invention provides a personalized corneal contact lens microneedle device for treating corneal ectasia diseases, comprising: a drug delivery device (2) and a fixing device (1), wherein the drug delivery device (2) comprises a drug delivery body (10) and a drug delivery microneedle (8) disposed on the drug delivery body; the fixing device (1) surrounds the periphery of the drug delivery body (10) and is concentric with and embedded in the drug delivery body (10);

[0047] The fixing device is used to be fixed on the corneal surface to fix the drug delivery body on the cornea in the thinned area. The drug delivery microneedle is used to penetrate the corneal epithelium to reach the corneal stroma layer to infiltrate the drug on the drug delivery body into the corneal stroma layer, and combined with ultraviolet light, achieve the therapeutic effect of increasing the thickness and hardness of the cornea in the thinned area.

[0048] During the cross-linking operation for treating corneal ectasia, the drug delivery microneedles on the central area penetrate the corneal epithelium to reach the corneal stroma, and the drug is infiltrated into the corneal stroma to achieve the therapeutic effect, without scraping the corneal epithelium, thus avoiding corneal epithelial damage and delivering a sufficient concentration of drug to the corneal stroma, and finally combined with ultraviolet irradiation to increase the thickness and hardness of the corneal stroma to control the progression of the disease. The present invention does not require the use of nano drugs, and the therapeutic effect is safe and efficient.

[0049] Furthermore, the fixing device (1) comprises a peripheral area (7), and the peripheral area is used to fit on the corneal surface to fix the personalized corneal contact lens microneedle device on the corneal surface.

[0050] It is understandable that the peripheral area is used to fit the corneal surface. In actual use, it can be made into different shapes (such as round, oval, etc.) according to the shape of the corneal epithelium of different patients to meet different usage requirements.

[0051] Furthermore, the fixing device (1) further comprises a fixing microneedle (6) arranged on the peripheral zone (7), wherein the fixing microneedle (6) is used to penetrate the corneal epithelium and the superficial stroma layer to fix the corneal contact lens device, so that the fixing zone is closely attached to the corneal surface around the corneal thinning area, and the fixing microneedle and the fixing zone control the corneal curvature through biomechanical action at the periphery of the cornea.

[0052] The present invention arranges fixed microneedles on the peripheral area, and the fixed microneedles apply force to the corneal surface to prevent the cornea from further expanding and thinning, reduce the corneal curvature to inhibit the progression of the corneal thinning area, shorten the arc length of the corneal thinning area, and reduce the abnormal corneal refractive power. Through the combined action of the drug delivery microneedles of the drug delivery device and the fixing device of the fixing device, the combined therapeutic effect of corneal biomechanical fixation and collagen cross-linking for corneal ectasia diseases is achieved, achieving the effect of 1+1>2.

[0053] Furthermore, the shape of the fixed microneedle (6) includes but is not limited to a "pine tree shape" or an "arrow shape".

[0054] Furthermore, the width of the peripheral area (7) is 8-28 mm, and the central thickness is 0.15-0.2 mm.

[0055] The overall coverage of the width of the peripheral zone of the present invention includes the cornea, the corneal limbus and the sclera to meet the corneal morphology requirements of various corneal ectasia diseases.

[0056] Furthermore, the peripheral zone (7) comprises a first rear surface facing the corneal surface and a front surface facing away from the corneal surface, wherein the first rear surface is a plane and the front surface is a curved surface.

[0057] The first rear surface of the peripheral zone of the personalized corneal contact lens microneedle device for treating corneal ectasia diseases of the present invention is a plane. When performing a cross-linking operation for treating corneal ectasia diseases, as the marginal zone and / or fixed microneedles are inserted into the corneal epithelium, the first rear surface changes from a plane to an arc surface with a certain curvature, thereby enhancing its fixing effect, fitting the corneal curvature, and stably fixing it to the cornea, and effectively shortening the arc length of the corneal thinning zone, preventing the cornea from further convexing and / or thinning, and maintaining the stability of the corneal curvature.

[0058] Furthermore, the peripheral area (7) includes a connection area, a fixing area (4), and an edge area (3) which are arranged in sequence from close to the drug delivery body to away from the drug delivery body, the connection area is connected to the drug delivery body, and the fixing microneedle (6) is arranged in the fixing area (4).

[0059] The edge zone of the present invention contacts the inner or outer side of the limbus and is used to fix and position the cornea or sclera, while preventing the fixing microneedles from damaging the limbus cells.

[0060] Furthermore, the fixing area (4) has a width of 3-4 mm and a thickness of 150-600 μm.

[0061] Furthermore, the fixing area (4) further comprises a second rear surface facing the corneal surface, the fixing microneedle (6) is arranged on the second rear surface, and the angle between the tangent line of the contact point of the second rear surface and the needle body of the fixing microneedle (6) is ≤90 o .

[0062] The fixing microneedle of the present invention is arranged on the second rear surface of the fixing area, and the width of the fixing area can be suitable for patients with thinning of the central cornea or thinning of the peripheral cornea. For patients with thinning of the central cornea, the fixing microneedle can be fixed at 0.2-0.6mm inside the limbus; when it is suitable for thinning of the peripheral cornea, the fixing microneedle can be fixed on the sclera at 1-4mm outside the limbus.

[0063] When the angle between the tangent line of the contact point of the second rear surface and the needle body of the fixed microneedle is ≤90 o When inserted into the corneal epithelium, the fixed microneedle is difficult to shift, thereby enhancing its fixation effect and achieving a mechanical effect similar to that of the corneal stroma ring.

[0064] Furthermore, the fixing area (4) further comprises a second rear surface facing the corneal surface, the fixing microneedle (6) is arranged on the second rear surface, and the angle between the tangent of the contact point of the second rear surface and the needle body of the fixing microneedle (6) is 5-45°.

[0065] When the angle between the tangent of the contact point of the second rear surface and the needle body of the fixed microneedle is 5-45°, the fixed microneedle is more difficult to shift after being inserted into the corneal epithelium, further enhancing its fixing effect.

[0066] Furthermore, the angle between the tangent line of the contact point of the second rear surface and the needle body of the fixed microneedle (6) is 15-30°.

[0067] Furthermore, the arc length of the front surface is 7-8.65 mm.

[0068] Furthermore, the width of the edge area (3) is 0.5-1 mm.

[0069] Furthermore, the fixed microneedle (6) has a needle tail diameter of 2.5-3.5 mm, a spacing of 0.1 mm, a needle head spacing of 0.5-0.9 mm, a needle body height of 0.4-0.7 mm, and a needle head diameter of 0.5-0.7 mm.

[0070] Furthermore, the drug delivery body (10) has a diameter of 4-10 mm and a thickness of 0.15-0.4 mm.

[0071] See also Figure 1 and Figure 2Furthermore, the drug delivery body (10) is provided with a first micropore, and the drug delivery microneedle (8) is provided with a second micropore, a liquid guide channel and a third micropore which are connected in sequence in the direction from the needle tail to the needle head. The needle tail of the drug delivery microneedle (8) is connected to the drug delivery body (10) so that the second micropore is connected to the first micropore. When the needle head of the drug delivery body (10) penetrates into the corneal stroma layer, the third micropore is used to penetrate the drug into the corneal stroma layer.

[0072] It can be understood that when the drug is added to the surface of the drug delivery body of the present invention, the drug can penetrate into the corneal stroma layer through the first micropore, the second micropore, the liquid guide channel and the third micropore.

[0073] When the present invention applies the contact lens microneedle device to the treatment of corneal ectasia diseases, a drug (such as riboflavin) is added to the drug delivery microneedle, and then the contact lens microneedle device loaded with the drug is worn on the patient's cornea. The drug delivery microneedle penetrates the corneal epithelium through minimally invasive surgery, and the needle reaches the corneal stroma. The drug penetrates into the corneal stroma from the micropores of the drug delivery microneedle, releasing the initial drug load, thereby achieving a therapeutic effect. When the effective concentration of the drug is not enough, the drug can be continuously dripped through the hollow micropores in the drug delivery device, and the drug enters the drug delivery microneedle from the hollow micropores in the central zone, and then enters the patient's corneal stroma from the micropores of the drug delivery microneedle, so that the drug reaches an effective concentration, and finally achieves safe and efficient delivery of riboflavin across the corneal epithelium.

[0074] When the effective concentration of the drug is not enough, the drug delivery device may have begun to degrade when the drug is continuously dripped through the hollow micropores in the drug delivery device. During the degradation of the drug delivery device, the drug can still be continuously delivered through the hollow structure of the microneedle until the drug reaches an effective concentration.

[0075] Furthermore, the drug delivery body (10) is provided with a first connecting portion, and the fixing device (1) is provided with a second connecting portion, and the second connecting portion is connected to the first connecting portion to connect the fixing device (1) to the drug delivery device (2).

[0076] As can be seen from the above, the fixing device (1) is connected to the drug delivery body (10) via the connection area of ​​the peripheral area (7), and therefore, the second connection portion is provided on the connection area of ​​the peripheral area (7).

[0077] See also Figure 3 Furthermore, the first connecting portion is one of a clip-on tip and a clip-on groove, and the second connecting portion is the other of the clip-on tip and the clip-on groove.

[0078] The drug delivery device of the present invention is connected to the fixing device through a snap-on tip and a snap-on groove. On the one hand, the fixing device and the drug delivery device can be kept stably connected. On the other hand, when performing a cross-linking operation for treating corneal ectasia diseases, the rear surface of the peripheral area changes from a flat surface to an arc surface with a certain curvature, which can still ensure a stable connection between the fixing device and the drug delivery device.

[0079] It can be understood that the first connection portion can also be a barb, a fishbone, etc., and the second connection portion can also be a barb, a fishbone, etc.

[0080] Furthermore, the drug delivery body (10) is provided with 3-5 hollow micropores.

[0081] Furthermore, the needle body height of the drug delivery microneedle (8) is 0.5-0.8 mm, the needle tail diameter is 0.7-0.9 mm, the spacing between the needle tails is 0.08-0.12 mm, and the needle head diameter is 0.5-0.7 mm.

[0082] Furthermore, the angle between the tangent line of the contact point between the drug delivery microneedle (8) and the drug delivery body (10) is 90 o .

[0083] The angle between the tangent line of the contact point between the drug delivery microneedle of the present invention and the drug loading subject is 90 o It is beneficial for drugs to penetrate into the corneal stroma.

[0084] Furthermore, in some embodiments of the present invention, the material of the fixing device (1) includes but is not limited to at least one of fluorosilicone-based polymers, polymethyl methacrylate, silicone hydrogel, and polyurethane.

[0085] Furthermore, the material of the drug delivery device (2) includes but is not limited to at least one of polylactic acid, polyhydroxyalkanoate, and polylactic acid-glycolic acid copolymer.

[0086] The fixing device and the drug delivery device of the present invention adopt different materials. The material of the drug delivery device is non-toxic and will not cause harm to the eye after degradation in the eye, and the degradation rate is relatively fast. When used for the treatment of corneal ectasia diseases, it will be completely degraded within 10-30 minutes; and the material of the fixing device is also non-toxic and will not cause harm to the eye after degradation in the eye, but relative to the material of the drug delivery device, the degradation rate of the material of the fixing device is relatively slow. When used for the treatment of corneal ectasia diseases, it will degrade in 7 days to 1 month, and the degradation rate can be controlled according to the mechanical changes of the patient's cornea. Therefore, the fixing device can be maintained in the eye for a long time to play a therapeutic role. The fixing microneedles of the fixing device prevent the cornea from further expanding and thinning by applying a force to the corneal surface, reduce the corneal curvature to inhibit the progression of the corneal thinning area, shorten the arc length of the corneal thinning area, and reduce the abnormal corneal refractive power.

[0087] The second aspect of the present invention provides a method for preparing a personalized corneal contact lens microneedle device for treating corneal ectasia diseases, comprising the following steps:

[0088] S1. Obtain different corneal morphological parameters for each person, and according to the corneal morphological parameters, manufacture a personalized drug delivery device (2) mold by 3D printing in accordance with the range of the corneal thinning area;

[0089] S2. Melting the material for preparing the drug delivery device (2), heating it to 150° C.-160° C., pouring it into a mold of the drug delivery device (2), removing bubbles, cooling and solidifying, and demolding to obtain the drug delivery device (2);

[0090] S3. Printing the fixture (1) using 3D printing technology, photocuring, and cleaning to obtain the fixture (1);

[0091] S4. The drug delivery device (2) and the fixing device (1) are tightly connected and cleaned and disinfected to obtain a corneal contact lens microneedle device for treating corneal ectasia diseases.

[0092] The present invention obtains corneal morphological parameters and, based on the corneal morphological parameters, 3D prints a drug delivery device mold, thereby preparing a personalized corneal contact lens microneedle device according to the different morphologies and characteristics of corneal dilation or thinning of different patients and the locations of corneal lesions in different patients, so that the corneal contact lens microneedle device fits more closely to the corneal surface, and the treatment site for corneal collagen cross-linking is personalized, which can better prevent the progression of the patient's dilated corneal disease, delay the surgical treatment time, and achieve the best therapeutic effect.

[0093] The present invention uses a 3D data scanner and other medical eye examination instruments to scan the patient's ocular surface, uses corneal topography and anterior segment OCT and other eye examinations to obtain and calculate corneal morphological parameters, obtain the patient's corneal morphological characteristics (including corneal morphology, central and peripheral corneal diameters, thickness, radius of curvature, base curve, height loss and other key parameters), and then uses 3D printing to produce a drug delivery device mold for a personalized corneal contact lens microneedle device for the treatment of corneal ectasia diseases that meets the corneal morphological characteristics and a 3D printed fixture.

[0094] Furthermore, in S3, the cleaning specifically includes: after light curing, immersing the fixture (1) in an isopropyl alcohol solution for cleaning to remove uncured resin and deposits.

[0095] Furthermore, in S4, the disinfection is carried out using ethylene oxide.

[0096] Furthermore, in S4, before the drug delivery device (2) and the fixing device (1) are engaged and connected, the drug delivery device (2) and the fixing device (1) are also cut, cleaned, polished and ground.

[0097] Figure 4 The microscopic morphology characterization and penetration ability test results of drug delivery microneedles. Figure 4 It can be seen that the drug delivery microneedle has a small needle body, a hollow channel inside, and can effectively penetrate into the agar. After penetration, the needle body does not deform and has good penetration power.

[0098] Figure 5 The dissolution of drug delivery microneedles within 30 minutes after contact with artificial tears. Figure 5 It can be seen that the drug delivery microneedles gradually dissolved after 10 minutes. At this time, the drug can still be dripped and delivered to the corneal stroma through the hollow microneedles. The microneedles are completely dissolved within 30 minutes.

[0099] Figure 6 To test the penetration ability of drug delivery microneedles in corneal tissue. Figure 6 It can be seen that the drug delivery microneedle effectively penetrates the corneal epithelium and reaches the corneal stroma. One day after the drug delivery microneedle is removed, the structure of the corneal epithelium and stroma gradually recovers. After three days, the corneal epithelium and stroma basically return to their original state. Among them, a represents that the drug delivery microneedle can effectively penetrate the corneal stroma and deliver the drug to the stroma after acting on the cornea; b represents that the corneal stroma has returned to its normal structure one day after the drug delivery microneedle is dissolved; c represents that the corneal epithelium and corneal stroma have all returned to their normal structure three days after the drug delivery microneedle is dissolved.

[0100] Figure 7 To investigate the in vivo biological safety and efficacy of a personalized contact lens microneedle device for the treatment of corneal ectasia. Figure 7 It can be seen that after using the microneedle corneal contact lens device, the corneal transparency is consistent with the blank control group, and no corneal damage or turbidity is shown. In addition, the corneal curvature of the same mouse cornea decreases before and after treatment. Among them, the blank control refers to the cornea without any intervention; the corneal contact lens microneedle means that after the corneal contact lens microneedle is applied, the cornea is transparent and smooth, with no obvious damage; before treatment means the morphology of the cornea before the corneal contact lens treatment; after treatment means that after the corneal contact lens, the corneal curvature is reduced and the convexity is suppressed.

[0101] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, ordinary technicians in the relevant field should understand that after reading the specification of this application, the technicians can still modify or replace the specific implementation mode of the present invention with equivalents, but these modifications or changes do not deviate from the scope of protection of the pending claims of the present application.

Claims

1. A personalized contact lens microneedle device for treating corneal ectasia, characterized in that: include: A drug delivery device, comprising a drug delivery body and a drug delivery microneedle disposed on the drug delivery body; A fixing device, surrounding the outer periphery of the drug delivery body and being concentric with and embedded in the drug delivery body; Among them, the fixing device is used to be fixed on the corneal surface to fix the drug delivery body on the thinned area of ​​the cornea, and the drug delivery microneedle is used to penetrate the corneal epithelium to reach the corneal stroma layer to penetrate the drug on the drug delivery body into the corneal stroma layer, and after combined with ultraviolet light irradiation, the therapeutic effect of increasing the thickness and hardness of the cornea in the thinned area is achieved.

2. The personalized corneal contact lens microneedle device for treating corneal ectasia according to claim 1, characterized in that: The fixing device comprises a peripheral area, and the peripheral area is used to fit on the corneal surface so as to fix the personalized corneal contact lens microneedle device on the corneal surface.

3. The personalized corneal contact lens microneedle device for treating corneal ectasia according to claim 1, characterized in that: The fixing device also includes a fixing microneedle disposed on the peripheral area, the fixing microneedle is used to penetrate the corneal epithelium and the shallow stroma layer to fix the corneal contact lens device, so that the fixing area is closely attached to the corneal surface around the corneal thinning area, and the fixing microneedle and the fixing area control the corneal curvature through biomechanical action at the periphery of the cornea. Preferably, the shape of the fixing microneedle includes but is not limited to "pine tree shape" or "arrow shape".

4. The personalized corneal contact lens microneedle device for treating corneal ectasia according to claim 3, characterized in that: The peripheral zone includes a first rear surface facing toward the corneal surface and a front surface facing away from the corneal surface, wherein the first rear surface is a plane and the front surface is a curved surface.

5. The personalized corneal contact lens microneedle device for treating corneal ectasia according to claim 3, characterized in that: The peripheral area includes a connection area, a fixing area, and an edge area which are sequentially arranged from close to the drug delivery body to far away from the drug delivery body. The connection area is connected to the drug delivery body, and the fixing microneedle is arranged in the fixing area.

6. The personalized corneal contact lens microneedle device for treating corneal ectasia according to claim 5, characterized in that: The fixing area further comprises a second rear surface for facing the corneal surface, the fixing microneedle is arranged on the second rear surface, and the angle between the tangent line of the contact point of the second rear surface and the needle body of the fixing microneedle is ≤90 o .

7. The personalized corneal contact lens microneedle device for treating corneal ectasia according to any one of claims 1 to 6, characterized in that: The drug delivery body is provided with a first micropore, and the drug delivery microneedle is provided with a second micropore, a liquid guide channel and a third micropore which are connected in sequence in the direction from the needle tail to the needle head. The needle tail of the drug delivery microneedle is connected to the drug delivery body so that the second micropore is connected to the first micropore. When the needle head of the drug delivery body penetrates into the corneal stroma layer, the third micropore is used to penetrate the drug into the corneal stroma layer.

8. The personalized corneal contact lens microneedle device for treating corneal ectasia according to any one of claims 1 to 6, characterized in that: The drug delivery body is provided with a first connection part, the fixing device is provided with a second connection part, and the second connection part is connected to the first connection part to connect the fixing device to the drug delivery device.

9. The personalized corneal contact lens microneedle device for treating corneal ectasia according to any one of claims 1 to 6, characterized in that: The material of the fixing device is not limited to at least one of fluorosilicone-based polymer, polymethyl methacrylate, silicone hydrogel, and polyurethane; The material of the drug delivery device includes, but is not limited to, at least one of polylactic acid, polyhydroxyalkanoate, and polylactic-co-glycolic acid.

10. The method for preparing a personalized corneal contact lens microneedle device for treating corneal ectasia according to any one of claims 1 to 9, characterized in that: The steps include: S1. Obtain different corneal morphological parameters for each person, and according to the corneal morphological parameters, make a personalized drug delivery device mold through 3D printing for the range of corneal thinning area; S2. The material for preparing the drug delivery device is melted, heated to 150°C-160°C, poured into a drug delivery device mold, bubbles are removed, cooled and solidified, and the drug delivery device is obtained after demolding; S3. Print the fixture using 3D printing technology, perform light curing, and clean the fixture to obtain the fixture; S4. The drug delivery device and the fixing device are tightly connected and cleaned and disinfected to obtain a corneal contact lens microneedle device for treating corneal ectasia diseases.

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