Eye microneedle cornea patch structure and mold for preparing eye microneedle cornea patch

Abstract

The utility model relates to the field of medical instruments, in particular to an eye microneedle cornea patch structure and a mold for preparing an eye microneedle cornea patch, which can prevent a microneedle on a microneedle substrate from damaging a cornea sclera marginal structure and cornea endothelial cells and further reduce damage to eyes of a patient in microneedle treatment. Comprising a microneedle substrate matched with an eyeball contour curved surface, a microneedle is arranged on the inner side wall face of the microneedle substrate and extends in the direction perpendicular to the inner side wall face of the microneedle substrate, a substrate through hole is formed in the geometric center of the microneedle substrate, the diameter of the microneedle substrate is smaller than that of a cornea, the diameter of the substrate through hole is not smaller than 4 mm, and the diameter of the substrate through hole is larger than or equal to 5 mm. And the microneedles are uniformly arranged on the microneedle substrate around the substrate through hole.

Description

TECHNICAL FIELD

[0001] The utility model relates to the field of medical apparatus and instruments, especially an eye micro-needle corneal patch structure and a mold for preparing the eye micro-needle corneal patch. BACKGROUND

[0002] The human eye is a complex and sensitive organ with static and dynamic ocular barriers. The anterior and posterior segment barriers hinder the passive absorption of drugs, thereby reducing the ocular bioavailability of drugs. Both the static barrier (corneal epithelium, corneal stroma, corneal endothelium, blood-aqueous barrier) and the dynamic barrier (tear dilution barrier, conjunctival barrier, and blood-retinal barrier) hinder drug absorption and affect the bioavailability of drugs. In addition, the shape of the human eye and the pre-corneal factors, such as blinking and tear secretion induced by drug stimulation, reduce the absorption of topically applied formulations. The absorption of ocular drugs can occur through two different routes, namely the corneal route and the non-corneal route. Most drugs are transported and absorbed within the eye through the corneal route, and the rest are absorbed through the nasolacrimal duct. Therefore, the absorption of drugs needs to effectively overcome the corneal epithelial cells. In view of the above drug absorption scenarios, the current micro-needle drug delivery system plays an important role in improving the efficacy of anti-glaucoma drugs. As a minimally invasive and painless drug delivery method with penetration, micro-needles can effectively penetrate the barrier of necrotic tissue or biological membrane, thereby improving the bioavailability of drugs.

[0003] For example, the application number is 202311739320.4, and the patent name is "Preparation method and application of antibacterial silk micro-needle patch imitating contact lenses". It discloses a micro-needle substrate that is adapted to the contour curve of the eyeball, and a structure in which micro-needles are uniformly arranged on the inner side wall surface of the micro-needle substrate. However, this structure cannot guarantee the transparency and non-invasiveness of the cornea in the pupil area under normal lighting conditions, and in actual use, it may damage the limbal barrier and cause pterygium and other ocular surface diseases. UTILITY MODEL CONTENT

[0004] The utility model solves the technical problem of providing an eye micro-needle corneal patch structure and a mold for preparing the eye micro-needle corneal patch that can prevent the micro-needles on the micro-needle substrate from damaging the limbal structure and corneal endothelial cells, thereby reducing the impact of micro-needle treatment on the eyes of patients.

[0005] The utility model solves the technical problem by adopting the following technical scheme: an eye micro-needle corneal patch structure, including a micro-needle substrate that is adapted to the contour curve of the eyeball, a micro-needle is arranged on the inner side wall surface of the micro-needle substrate, the micro-needle extends in a direction perpendicular to the inner side wall surface of the micro-needle substrate, a substrate through hole is arranged at the geometric center of the micro-needle substrate, the diameter of the micro-needle substrate is smaller than the diameter of the cornea, the area of the substrate through hole is not less than 4mm, and the micro-needles are uniformly arranged on the micro-needle substrate around the substrate through hole.

[0006] Further, the microneedle comprises a drug needle tip, which is arranged at the needle tip of the microneedle.

[0007] Further, the arrangement structure of the microneedle is an inner layer and an outer layer, and the microneedles in the inner layer and the outer layer are uniformly arranged around the through hole of the substrate.

[0008] Further, the diameter of the cornea is usually 10-12mm, in order to avoid damage to the limbus, the diameter of the microneedle substrate is smaller than the diameter of the cornea, and preferably the diameter of the microneedle substrate is 8-9mm.

[0009] The central optical zone is the area of 2.5-4.0mm in diameter in the center under normal light, which is very close to the spherical surface, and the curvature change range is less than 0.25D, which is one of the most important refractive media. In order to avoid damage to the cornea in the pupil area under normal light conditions, the diameter of the through hole of the substrate is not less than 4mm, and the diameter of the through hole of the substrate is preferably 4-5mm.

[0010] The normal corneal thickness is usually between 0.5-0.55mm (central optical zone) and 0.7-1.0mm (peripheral non-optical zone). In the utility model, the microneedle setting area is the peripheral non-optical zone, in order to avoid loss of corneal endothelium, the height of the microneedle is smaller than the thickness of the peripheral non-optical zone of the cornea, and the height of the microneedle is preferably 400-600μm.

[0011] The mold for preparing the ocular microneedle corneal patch comprises an upper mold and a lower mold, the top surface of the lower mold is provided with a lower mold top curved surface matched with the curved surface of the eyeball contour, the lower mold top curved surface is an upward convex structure, the upper mold comprises a substrate injection hole arranged in the vertical direction, the substrate injection hole is arranged at the geometric center of the upper mold, the upper mold comprises an upper mold convex column coaxially arranged with the substrate injection hole, the upper mold convex column extends downward and protrudes from the inner wall surface of the upper mold, the convex column bottom curved surface of the bottom surface of the upper mold convex column matches with the lower mold top curved surface, and a gap is arranged between the convex column bottom curved surface and the lower mold top curved surface.

[0012] Further, the lower mold top curved surface is uniformly provided with a needle tip drug groove along the direction around the geometric center of the lower mold top curved surface.

[0013] Further, the bottom surface of the upper mold is provided with an annular limiting boss, and the top surface of the lower mold is provided with an annular limiting groove, and the limiting boss and the limiting groove match with each other.

[0014] Further, the bottom surface of the upper mold is provided with at least one buckle, and the buckle is clamped in the clamping groove on the top surface of the lower mold.

[0015] The micro-needle base plate of the present scheme has a ring structure, no micro-needle is arranged at the middle base plate through hole, and the diameter of the base plate through hole is not less than 4 mm, so that the transparency and non-injury of the cornea in the pupil area under normal illumination conditions can be ensured, the diameter of the micro-needle base plate is less than the diameter of the cornea, in actual use, the micro-needle base plate can avoid the limbus area, avoid damaging the limbal barrier, so as to avoid the occurrence of pterygium and other ocular surface diseases, and the height of the micro-needle arranged on the ring-shaped micro-needle base plate is less than the thickness of the cornea, so that the needle tip drug can act on the cornea and the corneal endothelium is not damaged, the drug application effect is ensured and the injury is minimized. The mold provided by the present application has a simple structure, is easy to operate, and is suitable for the preparation of the ocular micro-needle corneal patch. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 is the top view of the upper mold and the lower mold of the present application tightly clamped and connected, and the micro-needle corneal patch prepared thereby.

[0017] Figure 2 is Figure 1 C-C cross-sectional view in the, the cross-sectional view respectively includes upper mold, the micro-needle corneal patch prepared and lower mold.

[0018] Figure 3 is Figure 2 A enlarged view of needle tip drug groove in

[0019] Figure 4 is the front view of the micro-needle corneal patch prepared.

[0020] In the figure, the marks are: upper mold 1, limiting boss 11, convex column bottom curved surface 12, upper mold convex column 121, base plate injection hole 13, buckle 14, lower mold 2, needle tip drug groove 21, lower mold top curved surface 22, limiting recess 23, ocular micro-needle corneal patch 3, micro-needle base plate 31, base plate through hole 32, micro-needle 33, drug needle tip 34. DETAILED DESCRIPTION

[0021] The present application will be further described below in combination with the drawings and examples.

[0022] As Figure 1 , Figure 2 , Figure 3 , Figure 4 shown, it is the embodiment of the ocular micro-needle corneal patch 3 and the mold structure for preparing the ocular micro-needle corneal patch 3.

[0023] The eye micro-needle corneal patch structure provided by the embodiment comprises a micro-needle substrate 31 matched with the contour curve of the eyeball, a micro-needle 33 is arranged on the inner side wall surface of the micro-needle substrate 31, the micro-needle 33 extends in a direction perpendicular to the inner side wall surface of the micro-needle substrate 31, a substrate through hole 32 is arranged at the geometric center of the micro-needle substrate 31, the diameter of the micro-needle substrate 31 is smaller than the diameter of the cornea, the diameter of the substrate through hole 32 is not less than 4 mm, and the micro-needle 33 is uniformly arranged on the micro-needle substrate 31 around the substrate through hole 32.

[0024] In the embodiment, the diameter of the micro-needle substrate 31 is 8 mm, and the diameter of the substrate through hole 32 is 4 mm.

[0025] The curved state of the eye micro-needle corneal patch 3 is matched with the curved state of the eye, so that the eye micro-needle corneal patch 3 can be well attached to the surface of the eyeball. The eye micro-needle corneal patch 3 is in the shape of a circular ring, a substrate through hole 32 is arranged at the geometric center of the eye micro-needle corneal patch 3, and a drug needle tip 34 is arranged around the outer periphery of the substrate through hole 32. The arrangement of the drug needle tip 34 is divided into an inner circle and an outer circle, which not only ensures uniform drug administration but also increases the amount of drug administered each time. In actual wearing, since the diameter of the micro-needle substrate 31 is smaller than the diameter of the cornea of the eyeball, the limbus of the cornea and the sclera will not be damaged. At the same time, since the diameter of the substrate through hole 32 is not less than 4 mm, the cornea in the pupil area will not be damaged by the micro-needle 33, and the drug administration area of the micro-needle 33 is limited to the area of the eyeball covered by the circular ring-shaped micro-needle substrate 31.

[0026] In the embodiment, the height of the micro-needle is 500 μm. At the tip of the micro-needle 33, a drug needle tip 34 made of the drug to be administered is arranged. The height of the drug needle tip 34 can be designed according to actual needs. Figure 2 As shown in the figure, the drug needle tip 34 is located at the needle tip part of the front end of the micro-needle 33. When the eye micro-needle corneal patch 3 is arranged on the eyeball of a patient, the drug needle tip 34 first contacts the surface of the eyeball of the patient and penetrates the corneal epithelial cell layer of the patient to administer the drug. This scheme can greatly reduce the damage to the eye of the patient, while ensuring that the drug successfully overcomes the corneal epithelial barrier to reach the patient's eye and is absorbed. In addition, this design also allows the micro-needle 33 to carry different drugs, that is, different drug needle tips 34 can be made of different drugs each time, and the drug needle tips 34 made of the drugs are arranged on the needle tip of the micro-needle 33. Compared with the traditional micro-needle which only administers a certain specific drug, the universality of the micro-needle 33 is greatly improved, the treatment cost of the micro-needle 33 is reduced, and the waste of materials is reduced.

[0027] Figure 2The embodiment of the mold structure for preparing the ocular microneedle corneal patch 3 is shown. The lower mold 2 top surface is provided with a lower mold top curved surface 22 which is adapted to the eyeball contour curved surface, and the lower mold top curved surface 22 is a structure that is convex upward. The upper mold 1 includes a substrate injection hole 13 arranged in the vertical direction, which is arranged at the geometric center of the upper mold 1. After the upper mold 1 is buckled with the lower mold 2, an internal cavity for casting the ocular microneedle corneal patch 3 is formed. The upper mold convex column 121 is coaxially arranged with the substrate injection hole 13, and the upper mold convex column 121 extends downward and protrudes from the inner wall surface of the upper mold 1, and the upper mold convex column 121 is used to form the substrate through hole 32 during casting. The convex column bottom curved surface 12 at the bottom surface of the upper mold convex column 121 matches the lower mold top curved surface 22, and a gap is arranged between the convex column bottom curved surface 12 and the lower mold top curved surface 22. The gap is used to guide the hydrogel material for forming the microneedle substrate 31 to flow from the substrate injection hole 13 to the above-mentioned cavity. In actual operation, the drug needs to be injected into the needle tip drug groove 21 first to form the subsequent drug needle tip 34, and then the above-mentioned casting operation is started. The limiting boss 11 and the top surface of the lower mold 2 are provided with an annular limiting groove 23 which matches each other to form a sealed structure, which not only can prevent the hydrogel from overflowing from the middle, but also can form capillary adsorption when the upper mold 1 and the lower mold 2 are attached, so that the upper and lower two layers are more easily adsorbed.

[0028] Referring to the above-mentioned mold structure, the steps for preparing the ocular microneedle corneal patch 3 are as follows: first, separate the upper mold 1 and the lower mold 2; second, inject the required drug into the needle tip drug groove 21 of the lower mold 2 using a syringe to form a drug needle tip 34 at the needle tip portion of the microneedle 33, and wait for the drug in the needle tip drug groove 21 to completely solidify before proceeding to the next step; then, combine the upper mold 1 and the lower mold 2 by three buckles 14, and inject the soluble biological macromolecules into the cavity formed by the upper mold 1 and the lower mold 2 through the substrate injection hole 13 using a syringe to form the microneedle substrate 31 portion, and wait for the microneedle substrate 31 to completely solidify; finally, after the microneedle substrate 31 is formed, the microneedle is demolded and the excess material is trimmed. For example, the excess material between the convex column bottom curved surface 12 and the lower mold top curved surface 22 is trimmed to obtain a complete substrate through hole 32, and the like, and finally a complete and smooth ocular microneedle corneal patch 3 is obtained.

[0029] As for the preparation of the upper mold 1 and the lower mold 2, the 3D printing projection microstereolithography (PμSL) technology can be used to quickly print the upper mold 1 and the lower mold 2 with an optical accuracy of 2 μm and a tolerance of ±10 μm. The upper mold 1 and the lower mold 2 are made of acrylic resin which has biocompatibility and high temperature resistance, such as Figure 1As shown, the mold is made by 3D printing light curing, which includes two parts, namely the upper mold 1 and the lower mold 2. The upper mold 1 and the lower mold 2 are tightly connected by three buckles 14 during use to ensure the accuracy of the preparation of the ocular microneedle corneal patch 3. The ocular microneedle corneal patch 3 manufactured by the 3D printing projection microstereolithography (PμSL) technology not only saves the manufacturing cost but also does not change the chemical and biological properties of the drug. The drug part of the ocular microneedle corneal patch 3 only exists in the microneedle tip part, and the microneedle substrate 31 part adopts a soluble biological macromolecule. This design increases the flexibility and safety of the ocular microneedle corneal patch 3, reduces the number of eye drug administrations, and reduces the trauma caused by eye drug administration, thereby providing a basis for the further application of the 3D printing manufacturing method in the clinic.

Claims

1. An ocular microneedle corneal patch structure comprising a microneedle substrate (31) adapted to the contour curve of the eyeball, the inner side wall surface of the microneedle substrate (31) is provided with microneedles (33), the microneedles (33) extend in a direction perpendicular to the inner side wall surface of the microneedle substrate (31), characterized in that: The geometric center of the microneedle substrate (31) is provided with a substrate through hole (32), the diameter of the microneedle substrate (31) is less than the diameter of the cornea, the diameter of the substrate through hole (32) is not less than 4mm, and the microneedles (33) are uniformly arranged on the microneedle substrate (31) around the substrate through hole (32). ​ 2. The ocular microneedle corneal patch structure of claim 1, wherein: The microneedle (33) comprises a drug needle tip (34) arranged at the needle tip of the microneedle (33).

3. The ocular microneedle corneal patch structure of claim 1 or 2, wherein: The arrangement structure of the microneedle (33) is two layers of inner and outer layers, and the microneedles of the inner layer and the microneedles of the outer layer are uniformly arranged around the substrate through hole (32).

4. The eye microneedle corneal patch structure of claim 1, wherein: The diameter of the microneedle substrate (31) is 8-9mm, and the diameter of the substrate through hole (32) is 4-5mm.

5. The eye microneedle corneal patch structure of claim 1, wherein: The height of the microneedle (33) is 400-600μm.

6. A mold for preparing an ocular microneedle corneal patch, comprising an upper mold (1) and a lower mold (2), wherein the top surface of the lower mold (2) is provided with a lower mold top curved surface (22) that is adapted to the contour curved surface of an eyeball, and the lower mold top curved surface (22) is a structure that is convex upward, and the upper mold (1) comprises a substrate injection hole (13) arranged in the vertical direction, and the substrate injection hole (13) is arranged at the geometric center of the upper mold (1), characterized in that: The upper die (1) comprises an upper die convex column (121), which is coaxially arranged with the substrate injection hole (13), and the upper die convex column (121) extends downward and protrudes from the inner wall surface of the upper die (1). The convex column bottom curved surface (12) at the bottom surface of the upper die convex column (121) matches the lower die top curved surface (22), and a gap is arranged between the convex column bottom curved surface (12) and the lower die top curved surface (22).

7. The mold for making ocular microneedle corneal patches of claim 6, wherein: The needle tip drug groove (21) is uniformly arranged on the lower die top curved surface (22) in the direction around the geometric center of the lower die top curved surface (22).

8. The mold for making ocular microneedle corneal patches of claim 6 or 7, wherein: The bottom surface of the upper die (1) is provided with an annular limiting boss (11), and the top surface of the lower die (2) is provided with an annular limiting groove (23), and the limiting boss (11) and the limiting groove (23) match each other.

9. The mold for making ocular microneedle corneal patches of claim 8, wherein: The bottom surface of the upper die (1) is provided with at least one buckle (14), which is clamped in the clamping groove on the top surface of the lower die (2).

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