Polyurethane artificial cornea material with porous skirt edge design and preparation method thereof
Prepolymers are generated by reaction of polymer polyols and diisocyanate, and combined with porous lace edge design, the problem of insecure fixation and fracture of artificial corneal materials is solved, high light transmittance and good biocompatibility are achieved, and it is suitable for artificial corneal materials.
Patent Information
- Application Number
- CN202510012423.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-06
- Publication Date
- 2025-08-05
AI Technical Summary
The existing artificial corneal materials are not firmly fixed after suture, the boundaries of the combined materials are prone to fracture, and the material's compatibility and light transmittance to cells are insufficient, resulting in a high risk of postoperative complications and shedding.
The polymer polyol and diisocyanate react to form prepolymers, followed by chain extension and cross-linking, and polyurethane artificial corneal material with porous scallops is designed. The same material is used in the light-transmitting area and scallops, which simplifies the preparation process and improves the bonding tightness of the material and cell growth space.
The prepared polyurethane elastomer has good mechanical properties, excellent optical properties, high light transmittance and good biocompatibility, which reduces the risk of fracture of the combined materials and enhances the fixing firmness of the corneal prosthesis and the binding tightness of the cells.
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Figure FT_1
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of elastomers, and in particular relates to a transparent polyurethane elastomer used for artificial cornea materials and a preparation method thereof. Background Art
[0002] Corneal transplantation is one of the effective methods for treating blindness caused by corneal damage, but the success rate of transplantation is very low due to factors such as the scarcity of natural corneas and autoimmune diseases. Using artificial corneas to replace natural corneas can effectively solve this problem.
[0003] Polyurethane is a polymer formed by the gradual polymerization of polymer polyols, polyisocyanates, small molecule polyols, etc. It has a hard-soft block structure, and the hard and soft segments are not easy to form a microphase separation structure due to thermodynamic incompatibility. The hard segment phase gives the material rigidity, and the soft segment phase provides flexibility. Therefore, polyurethane exhibits many excellent properties, such as low temperature resistance, wear resistance and a wide hardness range. In addition, the polyurethane formula can be adjusted according to the requirements of use, and polyurethane can be easily modified, so it is extremely widely used.
[0004] Artificial corneas place extremely high demands on the optical properties of the material. They also require certain mechanical properties and elasticity to prevent crushing and loss of the artificial cornea. Furthermore, the material must be non-toxic to cells and allow for cell growth within the material. The performance of polyurethane materials is directly related to the ratio of their raw materials. Adjusting the hard segment content in the raw materials can control the phase separation of the material. Phase separation in polyurethane materials is similar to a physical cross-linked network. When the material is subjected to external forces, it disperses the forces and improves its mechanical properties. The flow of soft segment chains in the material also provides excellent tensile properties. Phase separation also hinders crystallization. When the phase separation domain is less than 30nm, the material exhibits transparency. To achieve a material that is non-toxic to living organisms, all raw materials used are non-toxic after complete reaction and do not emit toxic substances at normal operating temperatures.
[0005] Numerous studies have investigated artificial cornea materials, but their inherent shortcomings have hindered their application. Heusser et al. used quartz glass to create artificial corneas and successfully transplanted them into humans, resulting in significant improvements in vision. However, due to poor cell adhesion and excessive material hardness, the material was squeezed and dislodged. Building on this, Cardona et al. attempted to create artificial corneas using PMMA, incorporating a "light-transmitting area-skirt" design. The PMMA skirt formed a "nut" attached to the cornea, with the optical components acting as "bolts." This design effectively secured the artificial cornea, but PMMA hindered nutrient flow, leading to a series of postoperative complications. Cell adhesion to the PMMA surface was also difficult, and the composite material was prone to fracture at the joints. Chirila et al. attempted to create a soft artificial cornea using PHEMA. This material has a larger porosity structure that allows nutrients to pass through and allows cells to adhere well to the surface. However, the high water content and large pores lead to insufficient suturing and poor overall mechanical properties, which can lead to corneal tears during surgical suturing. The most widely used material at present is the Boston prosthesis, but it is also expensive and has serious postoperative complications. In addition, there are few reports on the application of polyurethane materials in the field of artificial corneas and the combination of porous skirt designs.
[0006] To address the challenges of existing technologies, a polyurethane artificial cornea material with a porous skirt has been designed. The high tensile strength and strength of the polyurethane elastomer prevent the corneal material from being squeezed and dislodged. Using the same material for the translucent area and the porous skirt allows for the flow of polymer chains between the two, creating a tighter bond and resolving the problem of fracturing at the interface of the combined materials. The porous skirt design allows cells to grow within the pores, securing the corneal prosthesis and preventing it from dislodging. Summary of the Invention
[0007] The present invention aims to overcome the shortcomings of the prior art and is intended to address the problems of corneal materials being loosely fixed after suturing and the boundary of the composite material being prone to fracture during use. This method has fewer reaction steps and lowers energy consumption. The polyurethane elastomer prepared by this method has excellent mechanical and optical properties, is non-toxic and harmless to living organisms, and can be used as a substitute material for artificial corneas. Furthermore, the porous skirt design provides space for cell growth, making the corneal prosthesis more securely fixed. The skirt and the light-transmitting area are made of the same material, allowing the composite material to be more tightly bonded at the boundary.
[0008] To achieve the above object, the technical solution adopted by the present invention is:
[0009] Add 69-76% of a polymer polyol to a reactor, vacuum dehydrate at 120°C for 2-4 hours, cool to 60-70°C, add 18-21% of a diisocyanate, and heat to 90°C for 1-2 hours to produce an isocyanate-terminated prepolymer. After the prepolymer cools to 60-70°C, add 6-10% of a small-molecule diol dissolved in a high-boiling-point dehydration solvent for chain extension. Continue the reaction at 90°C for 1-2 hours, then degas for 1 hour until no significant bubbles rise from the bottom of the reactor. After the reaction system cools to 60-70°C, slowly add <1% of a crosslinker in multiple additions for crosslinking. Ensure rapid stirring during addition to ensure thorough mixing. Continue the reaction for 10-20 minutes, then degas until no significant bubbles rise from the bottom of the reactor. Cast the mixture and allow it to sit in a dry environment for 1-2 days. Finally, heat it in a high-temperature drying oven at 100°C for 10 hours to produce a polyurethane elastomer. A 6mm diameter disc is removed from the obtained polyurethane elastomer film and used as the light-transmitting area in the middle of the corneal prosthesis. The reaction is then carried out according to the same formula. An appropriate amount of water is added and poured around the disc. The corneal prosthesis material with a foamed skirt is obtained by heating it in an oven at 100°C for 10 hours.
[0010] The polymer polyol is polytetramethylene ether glycol, and the molecular weight of the polymer polyol is 1000.
[0011] The diisocyanate is hexamethylene diisocyanate.
[0012] The high boiling point solvent is dehydrated nitrogen-nitrogen dimethylacetamide.
[0013] The chain extender is bisphenol A containing a benzene ring and a side methyl structure.
[0014] The cross-linking agent is anhydrous glycerin after vacuum dehydration.
[0015] The ratio of the raw materials is such that the content of the hard segment in the reaction system is controlled within 25-31%.
[0016] In the process of making the skirt edge, the light-transmitting area disc should be used as soon as possible after being cut, and the skirt edge raw material should be fully stirred after adding water before pouring.
[0017] By adopting the above technical solution, the present invention first reacts a polymer polyol and a diisocyanate to form a prepolymer, then uses a sterically hindered chain extender for chain extension, and finally adds a crosslinking agent for crosslinking to obtain a polyurethane elastomer. Furthermore, a perforated skirt design is designed.
[0018] Compared with the prior art, the present invention has the following positive effects:
[0019] (1) In the preparation method adopted by the present invention, a polymer polyol and a diisocyanate are reacted to obtain a prepolymer, and then the prepolymer is chain extended and cross-linked, which reduces the synthesis steps, simplifies the process, and is conducive to industrial production.
[0020] (2) The mechanical properties of the polyurethane elastomer used in artificial cornea materials prepared by the present invention can be adjusted, with a strength range of 8 to 20 MPa and an elongation of 900 to 1800%, which can meet the needs of cornea materials.
[0021] (3) The polyurethane elastomer prepared by the present invention and used for artificial cornea materials has excellent optical properties, and its transmittance in the visible light region is above 90%, which can meet the needs of cornea materials.
[0022] (4) The materials used in the polyurethane elastomer used in the artificial cornea material prepared by the present invention are non-toxic to the organism after complete reaction.
[0023] (5) In the polyurethane elastomer prepared by the present invention and used in artificial corneal materials, the porous skirt edge design can provide space for cell growth, making the corneal prosthesis more firmly fixed. The same material used for the skirt edge and the light-transmitting area can also make the combined materials more tightly combined at the boundary.
[0024] Therefore, the preparation method of the artificial cornea structure polyurethane elastomer in the present invention has fewer synthesis steps and simplifies the process; the prepared artificial cornea structure polyurethane elastomer has good mechanical properties, excellent optical properties, is non-toxic to organisms, the combination of the prosthesis and human cells is more closely integrated, the combination of the combined materials is more firmly integrated, and the application prospects are broad. BRIEF DESCRIPTION OF THE DRAWINGS
[0025] Figure 1 : The prepared corneal prosthesis material with a porous skirt edge has a central part that is an optically transparent area and a surrounding porous skirt edge area. DETAILED DESCRIPTION
[0026] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited thereto.
[0027] Example 1
[0028] Add 69-76% of a polymer polyol to a reactor, vacuum dehydrate at 120°C for 2-4 hours, cool to 60-70°C, add 18-21% of a diisocyanate, and heat to 90°C for 1-2 hours to produce an isocyanate-terminated prepolymer. After the prepolymer cools to 60-70°C, add 6-10% of a small-molecule diol dissolved in a high-boiling-point dehydration solvent for chain extension. Continue the reaction at 90°C for 1-2 hours, then degas for 1 hour until no significant bubbles rise from the bottom of the reactor. After the reaction system cools to 60-70°C, slowly add <1% of a crosslinker in multiple additions for crosslinking. Ensure rapid stirring during addition to ensure thorough mixing. Continue the reaction for 10-20 minutes, then degas until no significant bubbles rise from the bottom of the reactor. Cast the mixture and allow it to sit in a dry environment for 1-2 days. Finally, heat it in a high-temperature drying oven at 100°C for 10 hours to produce a polyurethane elastomer.
[0029] In this embodiment, the proportions of the raw materials are: polytetramethylene ether glycol accounts for 75%, hexamethylene diisocyanate accounts for 18%, bisphenol A accounts for 6%, and anhydrous glycerin accounts for 0.42%.
[0030] The transparent polyurethane elastomer used for artificial cornea prepared in this embodiment was tested to have a tensile strength of 8-12 MPa, a visible light transmittance of 92-97%, and a cell survival rate of corneal epithelial cells of 96%.
[0031] Example 2
[0032] Add 69-76% of a polymer polyol to a reactor, vacuum dehydrate at 120°C for 2-4 hours, cool to 60-70°C, add 18-21% of a diisocyanate, and heat to 90°C for 1-2 hours to produce an isocyanate-terminated prepolymer. After the prepolymer cools to 60-70°C, add 6-10% of a small-molecule diol dissolved in a high-boiling-point dehydration solvent for chain extension. Continue the reaction at 90°C for 1-2 hours, then degas for 1 hour until no significant bubbles rise from the bottom of the reactor. After the reaction system cools to 60-70°C, slowly add <1% of a crosslinker in multiple additions for crosslinking. Ensure rapid stirring during addition to ensure thorough mixing. Continue the reaction for 10-20 minutes, then degas until no significant bubbles rise from the bottom of the reactor. Cast the mixture and allow it to sit in a dry environment for 1-2 days. Finally, heat it in a high-temperature drying oven at 100°C for 10 hours to produce a polyurethane elastomer.
[0033] In this embodiment, the proportions of the raw materials are: polytetramethylene ether glycol accounts for 72%, hexamethylene diisocyanate accounts for 20%, bisphenol A accounts for 8%, and anhydrous glycerin accounts for 0.57%.
[0034] The transparent polyurethane elastomer used for artificial cornea prepared in this embodiment was tested to have a tensile strength of 20-24 MPa, a visible light transmittance of 90-95%, and a cell survival rate of corneal epithelial cells of 64%.
[0035] Example 3
[0036] Add 69-76% of a polymer polyol to a reactor, vacuum dehydrate at 120°C for 2-4 hours, cool to 60-70°C, add 18-21% of a diisocyanate, and heat to 90°C for 1-2 hours to produce an isocyanate-terminated prepolymer. After the prepolymer cools to 60-70°C, add 6-10% of a small-molecule diol dissolved in a high-boiling-point dehydration solvent for chain extension. Continue the reaction at 90°C for 1-2 hours, then degas for 1 hour until no significant bubbles rise from the bottom of the reactor. After the reaction system cools to 60-70°C, slowly add <1% of a crosslinker in multiple additions for crosslinking. Ensure rapid stirring during addition to ensure thorough mixing. Continue the reaction for 10-20 minutes, then degas until no significant bubbles rise from the bottom of the reactor. Cast the mixture and allow it to dry for 1-2 days before heating it in a high-temperature drying oven at 100°C for 10 hours to produce a polyurethane elastomer.
[0037] In this embodiment, the proportions of the raw materials are: polytetramethylene ether glycol accounts for 69%, hexamethylene diisocyanate accounts for 21%, bisphenol A accounts for 10%, and anhydrous glycerin accounts for 0.63%.
[0038] The transparent polyurethane elastomer used for artificial cornea prepared in this embodiment was tested to have a tensile strength of 5-9 MPa, a visible light transmittance of 95-99%, and a cell survival rate of corneal epithelial cells of 94%.
[0039] Compared with the prior art, the present invention has the following positive effects:
[0040] (1) In the preparation method adopted by the present invention, a polymer polyol and a diisocyanate are reacted to obtain a prepolymer, and then the prepolymer is chain extended and cross-linked, which reduces the synthesis steps, simplifies the process, and is conducive to industrial production.
[0041] (2) The mechanical properties of the polyurethane elastomer of the artificial cornea structure prepared by the present invention can be adjusted, with a strength range of 8 to 20 MPa and an elongation of 900 to 1800%, which can meet the needs of corneal materials.
[0042] (3) The polyurethane elastomer of the artificial cornea structure prepared by the present invention has excellent optical properties, and its transmittance in the visible light region is above 90%, which can meet the needs of corneal materials.
[0043] (4) The materials used in the polyurethane elastomer of the artificial cornea structure prepared by the present invention are non-toxic to the organism after complete reaction.
[0044] (5) In the polyurethane elastomer prepared by the present invention and used in artificial corneal materials, the porous skirt edge design can provide space for cell growth, making the corneal prosthesis more firmly fixed. The same material used for the skirt edge and the light-transmitting area can also make the combined materials more tightly combined at the boundary.
[0045] Therefore, the preparation method of the artificial cornea structure polyurethane elastomer in the present invention has fewer synthesis steps and simplifies the process; the prepared artificial cornea structure polyurethane elastomer has good mechanical properties, excellent optical properties, is non-toxic to organisms, the combination of the prosthesis and human cells is more closely integrated, the combination of the combined materials is more firmly integrated, and the application prospects are broad.
Claims
1. A polyurethane artificial cornea material with a porous skirt design and a preparation method thereof, characterized by: Add 69-76% of a polymer polyol to a reactor, vacuum dehydrate at 120°C for 2-4 hours, cool to 60-70°C, add 18-21% of a diisocyanate, and heat to 90°C for 1-2 hours to produce an isocyanate-terminated prepolymer. After the prepolymer cools to 60-70°C, add 6-10% of a small-molecule diol dissolved in a high-boiling-point dehydration solvent for chain extension. Continue the reaction at 90°C for 1-2 hours, then degas for 1 hour until no significant bubbles rise from the bottom of the reactor. After the reaction system cools to 60-70°C, slowly add <1% of a crosslinker in multiple additions for crosslinking. Ensure rapid stirring during addition to ensure thorough mixing. Continue the reaction for 10-20 minutes, then degas until no significant bubbles rise from the bottom of the reactor. Cast the mixture and allow it to dry for 1-2 days. Finally, heat it in a high-temperature drying oven at 100°C for 10 hours to produce a polyurethane elastomer. A 6mm diameter disc is removed from the obtained polyurethane elastomer film and used as the light-transmitting area in the middle of the corneal prosthesis. The reaction is then carried out according to the same formula, and 20% water is added and poured around the disc. The corneal prosthesis material with a foamed skirt is obtained by heating it in an oven at 100°C for 10 hours.
2. The polyurethane artificial cornea material with a porous skirt design and its preparation method according to claim 1, characterized in that The polymer polyol is polytetramethylene ether glycol, and the molecular weight of the polymer polyol is 1000.
3. The polyurethane artificial cornea material with a porous skirt design and the preparation method thereof according to claim 1, characterized in that The diisocyanate is hexamethylene diisocyanate.
4. The polyurethane artificial cornea material with a porous skirt design and the preparation method thereof according to claim 1, characterized in that The high boiling point solvent is dehydrated N,N-dimethylacetamide.
5. The polyurethane artificial cornea material with a porous skirt design and its preparation method according to claim 1, characterized in that The chain extender is bisphenol A containing a benzene ring and a side methyl structure.
6. The polyurethane artificial cornea material with a porous skirt design and the preparation method thereof according to claim 1, characterized in that The cross-linking agent is anhydrous glycerin after vacuum dehydration.
7. The polyurethane artificial cornea material with a porous skirt design and the preparation method thereof according to claim 1, characterized in that The ratio of raw materials is controlled so that the mass percentage of the hard segment in the reaction system is controlled within 25-31%.
8. The polyurethane artificial cornea material with a porous skirt design and the preparation method thereof according to claim 1, characterized in that In the process of making the skirt edge, the transparent area disc should be used as soon as possible after being cut off, and the skirt edge raw materials should be fully stirred after adding water before pouring.