Amniotic membrane mirror with low foreign body sensation and preparation method of amniotic membrane mirror

Abstract

The invention provides an amniotic membrane mirror with low foreign body sensation and a preparation method thereof.The amniotic membrane mirror is composed of a large ring, a small ring and a biological amniotic membrane, the inner side of the large ring is provided with a weft groove and a warp groove, the biological amniotic membrane is located between the large ring and the small ring, the small ring is embedded into the weft groove of the large ring to clamp and fix the biological amniotic membrane to the inner side of the large ring, and the small ring is embedded into the warp groove of the large ring to clamp and fix the biological amniotic membrane to the inner side of the large ring. The large ring is made of soft materials, the small ring is made of hard materials, after the biological amniotic membrane is clamped and fixed through the large ring and the small ring, a patient wears the biological amniotic membrane in an amniotic membrane mirror mode, the large ring with the largest contact area with the ocular surface is made of the soft materials, foreign body sensation after wearing can be greatly reduced, and the biological amniotic membrane has wide application prospects and is beneficial to application and popularization.

Description

Technical Field

[0001] The invention belongs to the category of medical products, and relates to a novel amniotic membrane mirror with low foreign body sensation and a preparation method thereof. The product can be used in the field of ophthalmic treatment. Background Art

[0002] As an allogeneic medical device, biological amniotic membrane has been widely used in the treatment of ophthalmic diseases such as pterygium, corneal ulcer, chemical burns, and symblepharon. At present, biological amniotic membrane is mainly divided into wet amniotic membrane and dry amniotic membrane. Among them, wet amniotic membrane is easy to shrink and is generally provided in the form of amniotic membrane attached to nitrocellulose filter membrane. Dry amniotic membrane is made by dehydrating and drying wet amniotic membrane. After drying, the amniotic membrane is not easy to shrink, so it can be packaged separately and does not require a fixing device. However, both dry and wet amniotic membranes are in wet form during clinical use, that is, dry amniotic membranes need to be rehydrated before use. The thin and soft characteristics of biological amniotic membrane make it curled and wrinkled, and it is very easy to shift and fall off after covering the wound on the ocular surface. Therefore, it is generally sutured with surrounding tissues using surgical sutures, or bonded with fibrin glue, and sometimes it is fixed with a bandage mirror. This has invisibly increased the difficulty of surgery and increased the patient's treatment expenses. Therefore, ophthalmic device developers use certain fixing devices to fix the biological amniotic membrane and make it into the style of corneal contact lenses, commonly known as "amniotic membrane lenses". It can be worn directly on the defective area of ​​the ocular surface, thus avoiding additional surgical operations such as suturing and gluing, and greatly reducing the operation time.

[0003] PROKERA ® It is the representative of this kind of products. It is composed of a large ring, a small ring and amniotic membrane. The large ring is made of hard material, while the small ring is made of elastic material. The amniotic membrane is firmly put on the large ring through the small ring, thus forming a trinity "amnioscope". Many invention patents at home and abroad are also modified on the basis of this design. However, this design has the following problems: because the large ring is made of hard material, the patient has a strong foreign body sensation after wearing it.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] The purpose of the present invention is to provide an amnionoscope with low foreign body sensation and a preparation method thereof, wherein the amnionoscope is composed of three parts: a "large ring" made of soft material, a "small ring" made of hard material, and biological amnion. After the biological amnion is clamped and fixed by the large ring and the small ring, the patient wears it in the form of an amnionoscope, wherein the "large ring" with the largest contact area with the ocular surface is made of soft material, which can greatly reduce the foreign body sensation after wearing, has broad application prospects, and is conducive to popularization and application.

[0006] In order to achieve the above-mentioned purpose, the present invention provides an amnionoscope with low foreign body sensation, which is composed of a large ring, a small ring and a biological amnion. The inner side of the large ring is provided with a latitudinal groove and a longitudinal groove. The biological amnion is located between the large ring and the small ring. The small ring is embedded in the latitudinal groove of the large ring to clamp and fix the biological amnion on the inner side of the large ring. The large ring is made of soft material, and the small ring is made of hard material.

[0007] Preferably, the large ring is trumpet-shaped, with a small upper end and a large lower end, and the cross-section of the rounded edges at the upper and lower ends is arc-shaped, and the curvature is the same as the curvature of the eye surface.

[0008] Preferably, the outer diameter of the small ring is 0-2 mm larger than the outer diameter of the latitudinal groove of the large ring, the maximum diameter of the small ring is not greater than the depth of the latitudinal groove of the large ring, and the small ring does not protrude from the latitudinal groove after assembly.

[0009] Preferably, the latitudinal groove of the large ring has a narrow-mouth structure design, that is, the width of the latitudinal groove of the large ring at the entrance is smaller than the width inside the latitudinal groove.

[0010] Preferably, the minimum cross-sectional diameter of the small ring is 0-2 mm larger than the width of the large ring at the entrance of the latitudinal groove, and the inner side of the small ring is a smooth curved surface, and its curved surface forms a smooth transitional curved surface with the inner curved surface of the large ring.

[0011] Preferably, the soft material of the macrocycle is polyhydroxyethyl methacrylate, hydroxyethyl methacrylate, a copolymer of methyl methacrylate and glyceryl acrylate, a copolymer of methyl methacrylate and N-vinyl pyrrolidone, polyvinyl alcohol or a silicone hydrogel material.

[0012] Preferably, the soft material of the macrocycle is a silicone hydrogel material.

[0013] Preferably, the hard material of the small ring is fluorosilicone acrylate material, polymethyl methacrylate material or silicone methacrylate material.

[0014] Preferably, the hard material of the small ring is a polymethyl methacrylate material.

[0015] Preferably, the biological amniotic membrane is natural amniotic membrane or amniotic membrane that has been decellularized, in a wet or dry state, and is taken from the placenta of a mammal, and the mammal is a human, a pig, a sheep, a horse or a cow.

[0016] Preferably, the biological amniotic membrane is a wet human amniotic membrane.

[0017] The present invention also provides a method for preparing the above-mentioned amnionoscope with low foreign body sensation, comprising the following steps: S1: First, the large ring and the small ring are prepared by milling, injection molding or 3D printing; S2: Then, special tools are used to assemble the biological amnion, the small ring and the large ring into an amnionoscope.

[0018] Preferably, the shape of the tool is similar to that of an eyeball, and the curvature of the biological amnion after the amnionoscope is assembled is similar to the curvature of the ocular surface.

[0019] The present invention provides an amnionoscope with low foreign body sensation and a preparation method thereof, which has the following beneficial effects: 1. Compared with the biological amniotic membrane fixation ring prepared by conventional technology, the product of the present invention adopts reverse innovation thinking. The "big ring" with a larger contact area with the ocular surface is made of soft material, and the supporting skeleton "small ring" is made of hard material. This design can greatly reduce the foreign body sensation of patients after wearing it.

[0020] 2. The latitudinal groove of the large ring of the present invention has a narrow-mouthed structural design. The small ring can be completely wrapped by the large ring after being embedded. Compared with the conventional open-mouth design, the probability of the small ring falling off the large ring is lower, thereby reducing the risk of treatment failure caused by the falling off of the small ring; the specially designed longitudinal groove on the inner side of the large ring can play a role in draining exudate, and is suitable for ocular surface wounds with exudate.

[0021] 3. The inner side of the small ring of the present invention is designed as a smooth curved surface, and its curved surface and the inner curved surface of the large ring form a smooth transitional curved surface. If the small ring accidentally falls off from the large ring during the process of the patient wearing the amniotic lens, the small ring with a smooth curved surface design will not cause damage to the ocular surface. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 is a top view of the macrocycle of the present invention; Figure 2 AA cross-sectional view of the macrocycle of the present invention; Figure 3 This is an enlarged schematic diagram of the narrow-mouth design of the latitudinal groove at the large ring I of the present invention; Figure 4 is a schematic diagram of the three-dimensional structure of the macrocycle of the present invention; Figure 5 Schematic diagram of the three-dimensional structure of the small ring of the present invention; Figure 6 is a top view of a small ring of the present invention; Figure 7 BB is a cross-sectional view of the small ring of the present invention; Figure 8 This is an enlarged schematic diagram of the inner smooth curved surface design of the small ring II of the present invention; Fig. 9 It is a schematic diagram of the (eyeball-shaped) tooling device used for assembling the amnionoscope of the present invention; Fig.10 This is a schematic diagram of the three-dimensional structure of the amnionoscope after assembly of the present invention; Fig.11 A top view of the assembled amnionoscope of the present invention; Fig.12 It is a CC cross-sectional view of the assembled amnionoscope of the present invention; Fig.13 It is an enlarged schematic diagram of position III of the amnionoscope after assembly of the present invention; Fig.14 Schematic diagram of the latitudinal grooves of the large ring of the amnionoscope assembled in Comparative Example 2 without a narrow mouth design; Fig.15 This is an enlarged schematic diagram of the large ring latitudinal groove IV of the amnioscopic device assembled in Comparative Example 2, which does not adopt a narrow-mouth design.

[0023] In the figure: 1. Large ring 2. Small ring 3. Biological amniotic membrane 4. Latitudinal groove 5. Meridian groove 6. Tooling equipment. DETAILED DESCRIPTION

[0024] The present invention is further described below in conjunction with specific embodiments and drawings to help understand the content of the present invention.

[0025] like Figure 1-Figure 4 As shown, it is a schematic diagram of the macrocycle of the present invention, such as Figure 5-Figure 8 As shown, it is a schematic diagram of the small ring of the present invention, Figure 10-13As shown, it is a schematic diagram of the amnioscope after the assembly of the present invention. The amnioscope with low foreign body sensation is composed of a large ring, a small ring and a biological amniotic membrane. The inner side of the large ring is provided with a latitudinal groove and a longitudinal groove. The biological amniotic membrane is located between the large ring and the small ring. The small ring is embedded in the latitudinal groove of the large ring to clamp and fix the biological amniotic membrane on the inner side of the large ring. The large ring is made of a soft material, and the small ring is made of a hard material. The large ring is trumpet-shaped, with a small upper end and a large lower end. The cross-section of the round edges at the upper and lower ends is arc-shaped, and its curvature is the same as the curvature of the eye surface. The outer diameter of the small ring is 0-2mm larger than the outer diameter of the latitudinal groove of the large ring, and the maximum diameter of the small ring is not greater than the depth of the latitudinal groove of the large ring. After assembly, the small ring does not protrude from the latitudinal groove. The latitudinal groove of the large ring has a narrow-mouthed structural design, that is, the width of the latitudinal groove of the large ring at the entrance is smaller than the width inside the latitudinal groove. The minimum cross-sectional diameter of the small ring is 0-2 mm larger than the width of the large ring at the entrance of the latitudinal groove. The inner side of the small ring is a smooth curved surface, and its arc surface is a smooth transitional curved surface with the inner arc surface of the large ring. The soft material of the large ring is polyhydroxyethyl methacrylate, hydroxyethyl methacrylate, copolymer of methyl methacrylate and glycerol acrylate, copolymer of methyl methacrylate and N-vinyl pyrrolidone, polyvinyl alcohol or silicone hydrogel material. Preferably, the soft material of the large ring is silicone hydrogel material. The hard material of the small ring is fluorosilicone acrylate material, polymethyl methacrylate material or silicone methacrylate material. Preferably, the hard material of the small ring is polymethyl methacrylate material. The biological amniotic membrane is natural amniotic membrane or decellularized amniotic membrane, in wet or dry state, which is taken from the placenta of a mammal, and the mammal is a human, pig, sheep, horse or cattle. Preferably, the biological amniotic membrane is a wet human amniotic membrane.

[0026] The present invention also provides a method for preparing the above-mentioned amnionoscope with low foreign body sensation, comprising the following steps: S1: First, the large ring and the small ring are prepared by milling, injection molding or 3D printing; S2: Then, a special tool is used to assemble the biological amnion, the small ring, and the large ring into an amnionoscope. The shape of the tool is similar to the eyeball, and after the amnionoscope is assembled, the curvature of the biological amnion is similar to the curvature of the eye surface. Fig. 9 Shown is a schematic diagram of the (eyeball-shaped) tooling used to assemble the amnioscopic apparatus of the present invention.

[0027] The experimental methods used in the following examples are all conventional methods unless otherwise specified; the materials, reagents, etc. used can be purchased from commercial channels unless otherwise specified; the preparation method of the biological amniotic membrane described in the present invention is based on the conventional methods mentioned in academic literature.

[0028] Example 1 A method for preparing a human amniotic membrane According to the conventional method, human placenta was obtained, the amniotic membrane was removed and the blood stains were cleaned to obtain human biological amniotic membrane (wet state); then, a macrocyclic ring made of poly(hydroxyethyl methacrylate) and a microcyclic ring made of fluorosilicone acrylate were prepared by injection molding, wherein the latitudinal groove of the macrocyclic ring was designed with a narrow mouth ( Figure 3 ), the inner side of the small ring is designed as a smooth curved surface, and its curved surface and the inner curved surface of the large ring form a smooth transition curved surface ( Figure 8 ); then use special tooling to assemble the above biological amnion with the small ring and the large ring into an amnionoscope.

[0029] Example 2 A method for preparing a porcine amniotic membrane First, a porcine placenta is taken, the amniotic membrane is peeled off to clean the blood stains, and the porcine decellularized biological amniotic membrane is prepared by the conventional decellularization method in the literature, and the dry biological amniotic membrane is obtained by vacuum freeze-drying; then, a large ring made of poly(hydroxyethyl methacrylate) and a small ring made of poly(methyl methacrylate) are processed according to the 3D printing process, wherein the latitudinal groove of the large ring adopts a narrow mouth design, and the inner side of the small ring is designed as a smooth curved surface, and its curved surface and the inner curved surface of the large ring form a smooth transition curved surface; then, special tooling is used to assemble the above-mentioned biological amniotic membrane with the small ring and the large ring into an amnionoscope.

[0030] Example 3 A method for preparing a bovine amniotic membrane First, a bovine placenta was obtained, the amniotic membrane was removed to clean the blood stains, and a single layer of bovine decellularized biological amniotic membrane was prepared using a conventional decellularization method in the literature. Then, a multilayer composite amniotic membrane was prepared using the following steps: First, a bovine placenta was obtained, the amniotic membrane was peeled off to clean the blood stains, and the bovine decellularized biological amniotic membrane (wet state) was prepared using the conventional decellularization method in the literature; then, a large ring made of silicone hydrogel and a small ring made of silicone methacrylate were processed using a turning and milling process, wherein the latitudinal groove of the large ring was designed with a narrow mouth, and the inner side of the small ring was designed as a smooth curved surface, and its curved surface formed a smooth transition curved surface with the inner curved surface of the large ring; then, special tooling was used to assemble the above-mentioned biological amniotic membrane with the small ring and the large ring into an amnionoscope.

[0031] Comparative Example 1 Preparation of traditional amniotic membrane fixation ring and foreign body stimulation test Because the large ring in the amnioscope is the component with the largest contact area with the ocular surface, this comparative example indirectly evaluates the foreign body effect of the amnioscope assembled by the large ring by conducting a foreign body stimulation test on the large ring. First, a large ring is prepared by injection molding process using polymethyl methacrylate, a hard material, as the raw material, to obtain a traditional amniotic fixation ring, which is used as the control group; the large ring prepared in Example 1 is taken as the experimental group. Both groups of samples are sterilized by ethylene oxide, and then a foreign body sensation test is performed. The specific method is as follows: 6 rabbits are taken, the animals are first conventionally anesthetized, and then the amnioscope large ring prepared in Example 1 or Comparative Example 1 is worn on the left and right eyes of the rabbits, respectively, and the conjunctival congestion of the animals is generally observed 3 days and 7 days after surgery. The experimental results show that 3 animals in the control group had obvious conjunctival congestion 3 days after surgery, and 1 animal was still slightly congested 7 days after surgery; while no conjunctival congestion was observed in the experimental group throughout the experiment. The test shows that compared with a hard material fixing ring prepared by conventional technology, the fixing ring made of soft material in the present invention has lower eye irritation effect.

[0032] Comparative Example 2 Preparation and stability comparison test of amnioscope without narrow mouth design The latitudinal groove of the large ring of the present invention has a narrow structure design, and the small ring can be wrapped by the large ring after being embedded in the groove to prevent the small ring from falling off. In order to verify that the small ring of the present invention has a lower shedding rate, a large ring with a wide groove is designed ( Figure 14-15 ), except that the structure of the groove is different, the other steps are all prepared by the method described in Example 1. Then, 10 samples of Comparative Example 2 and Example 1 are taken, placed in a conical flask filled with physiological saline, and oscillated at 37°C for 7 days at an oscillation speed of 50 rpm to simulate the dynamic use of the amnionoscope on the patient's ocular surface in vitro, and after 7 days, observe whether the small ring falls off from the large ring. The results showed that in 2 samples of Comparative Example 2, the small ring fell off from the groove of the large ring (the shedding rate was 20%), while no shedding was found in Example 1. This test shows that the narrow groove design of the present invention can reduce the risk of the small ring falling off from the large ring, and the amniotic membrane can be more stably fixed between the two rings.

[0033] The invention concept is described in detail using specific examples herein, and the description of the above embodiments is only used to help understand the core idea of ​​the invention. It should be pointed out that any obvious modification, equivalent substitution or other improvement made by a person of ordinary skill in the art without departing from the invention concept should be included in the protection scope of the present invention.

Claims

1. An amnioscopic instrument with low foreign body sensation, characterized in that: It consists of a large ring, a small ring and a biological amniotic membrane. The inner side of the large ring is provided with a latitudinal groove and a longitudinal groove. The biological amniotic membrane is located between the large ring and the small ring. The small ring is embedded in the latitudinal groove of the large ring to clamp and fix the biological amniotic membrane on the inner side of the large ring. The large ring is made of soft material, and the small ring is made of hard material.

2. The low foreign body sensation amnioscope according to claim 1, characterized in that: The large ring is trumpet-shaped, with a small upper end and a large lower end. The cross-sections of the round edges at the upper and lower ends are arc-shaped, and the curvature is the same as the curvature of the eye surface.

3. The low foreign body sensation amnioscope according to claim 2, characterized in that: The outer diameter of the small ring is 0-2mm larger than the outer diameter of the latitudinal groove of the large ring, the maximum diameter of the small ring is not greater than the depth of the latitudinal groove of the large ring, and the small ring does not protrude from the latitudinal groove after assembly.

4. The low foreign body sensation amnioscope according to claim 3, characterized in that: The latitudinal groove of the large ring has a narrow-mouth structure design, that is, the width of the latitudinal groove of the large ring at the entrance is smaller than the width inside the latitudinal groove.

5. The low foreign body sensation amnioscope according to claim 4, characterized in that: The minimum cross-sectional diameter of the small ring is 0-2 mm larger than the width of the large ring at the entrance of the latitudinal groove. The inner side of the small ring is a smooth curved surface, and its curved surface and the inner curved surface of the large ring form a smooth transition curved surface.

6. The low foreign body sensation amnioscope according to claim 5, characterized in that: The soft material of the macrocycle is polyhydroxyethyl methacrylate, hydroxyethyl methacrylate, a copolymer of methyl methacrylate and glyceryl acrylate, a copolymer of methyl methacrylate and N-vinyl pyrrolidone, polyvinyl alcohol or a silicone hydrogel material.

7. The low foreign body sensation amnioscope according to claim 6, characterized in that: The hard material of the small ring is fluorosilicone acrylate material, polymethyl methacrylate material or silicone methacrylate material.

8. The low foreign body sensation amnioscope according to claim 7, characterized in that: The biological amniotic membrane is natural amniotic membrane or amniotic membrane after decellularization, in wet or dry state, and is taken from the placenta of a mammal, and the mammal is a human, a pig, a sheep, a horse or a cow.

9. A method for preparing an amnionoscope with low foreign body sensation according to any one of claims 1 to 8, characterized in that: The steps include: S1: First, the large ring and the small ring are prepared by milling, injection molding or 3D printing; S2: Then, special tools are used to assemble the biological amnion, the small ring and the large ring into an amnionoscope.

10. The method for preparing an amnionoscope with low foreign body sensation according to claim 9, characterized in that: The shape of the tool is similar to that of an eyeball, and after the amnionoscope is assembled, the curvature of the biological amnion is similar to that of the ocular surface.

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