CN108578768B - High-strength injectable intraocular lens material and preparation method and application thereof - Google Patents
High-strength injectable intraocular lens material and preparation method and application thereof Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F226/06—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a heterocyclic ring containing nitrogen
- C08F226/10—N-Vinyl-pyrrolidone
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
- C08F283/06—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals
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- A—HUMAN NECESSITIES
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- A—HUMAN NECESSITIES
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/43—Hormones, e.g. dexamethasone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea
Abstract
The invention discloses a high-strength injectable intraocular lens material and a preparation method and application thereof, and solves the problems that the injectable human crystalline lens in the prior art has poor physical and mechanical strength and can not avoid potential complications after cataract surgery. The artificial lens material is formed by polymerizing four monomers, wherein the four monomers are respectively a temperature-sensitive functional monomer, an acrylate monomer, a prodrug monomer and a cross-linking agent. The preparation method comprises the steps of mixing the temperature-sensitive functional monomer, the acrylate monomer, the prodrug monomer, the cross-linking agent and the initiator, reacting at 50-100 ℃ for 0.5-24 hours, and separating the product to remove the unreacted small molecular monomer. The artificial lens material provided by the invention is scientific in composition and reasonable in proportion, and all components play a role together, so that the prepared artificial lens material has good mechanical strength and optical performance, and can effectively reduce complications of ophthalmic surgery.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a high-strength injectable intraocular lens material as well as a preparation method and application thereof.
Background
Cataract is a common eye disease of middle-aged and elderly people, mainly manifested as lens per se or lens capsule opacity, and patients can be recovered clinically only by means of operations, i.e. cataract extraction and artificial lens implantation. Although cataract surgery is now well established, there are still some potential postoperative complications that may lead to postoperative vision loss and even blindness; such as postoperative endophthalmitis and secondary cataract.
Intraocular lenses are classified into rigid intraocular lenses and foldable intraocular lenses according to their hardness. The main material of the hard artificial lens is Polymethacrylate (PMMA), which has the characteristic of good optical performance, but has a plurality of limitations in operation because the hardness is high and the cornea is easy to be damaged. However, foldable intraocular lenses are limited by materials and implantation methods, and are prone to glare problems and post-cataract.
The patent with the application number of 201610929032.9, an injectable temperature-sensitive hydrogel intraocular lens material with cell membrane bionics and a preparation method thereof, discloses a lens material which can be implanted into a human body through injection. However, in order to ensure the injectability of the material, the physical and mechanical strength of the material is insufficient, and the using effect is influenced. Meanwhile, the material also has the function of reducing ophthalmic surgery complications.
In order to alleviate complications caused by ophthalmic surgery, eye drops are often used clinically. Since the eye is a relatively independent organ with its own barrier and protective system, the drug is lost through tears and blinks, resulting in poor bioavailability of the drug in the conventional dosage form. The half-life period of the anti-inflammatory drug in the vitreous body is short, and the anti-inflammatory drug can achieve the treatment effect on the disease of the back end of the eye with longer disease course by multiple drug administration, thereby increasing other side effects of the eye and reducing the medication compliance of patients.
Therefore, it is an urgent need to provide a high strength injectable intraocular lens material which can be implanted into the eye by injection to reduce the damage to the human body, has physical and mechanical strength, and can effectively reduce the complications of ophthalmic surgery.
Disclosure of Invention
The technical problem solved by the invention is as follows: provides a high-strength injectable intraocular lens material, which solves the problems that the injectable human crystalline lens in the prior art has poor physical and mechanical strength and can not avoid potential complications after cataract surgery.
The invention provides a preparation method of a high-strength injectable intraocular lens material.
The invention provides an application of a high-strength injectable intraocular lens material.
The technical scheme adopted by the invention is as follows:
the high-strength injectable intraocular lens material is prepared by polymerizing four monomers, wherein the four monomers are a temperature-sensitive functional monomer, an acrylate monomer, a prodrug monomer and a cross-linking agent.
Further, the temperature-sensitive functional monomer is selected from one of N-isopropyl acrylamide, vinyl pyrrolidone and dimethylaminoethyl methacrylate.
Further, the prodrug monomer is a derivative of an anti-inflammatory drug having a polymerizable double bond.
Further, the anti-inflammatory drug is one selected from indomethacin, levofloxacin, diclofenac, ribavirin, dexamethasone, ganciclovir, chloramphenicol, norfloxacin, prednisone, acyclovir and lanosterol.
Further, the cross-linking agent is one of ethylene glycol dimethacrylate, butanediol dimethacrylate, hexanediol acrylate, or diethylene glycol diacrylate.
Further, the sum of the total mass percentage of the four monomers is 100%, the content of the temperature-sensitive functional monomer is 20-45 wt%, the content of the acrylate monomer is 20-45 wt%, the content of the prodrug monomer is 10-35 wt%, and the content of the cross-linking agent is 0.1-5 wt%.
The preparation method of the high-strength injectable intraocular lens material is characterized in that the temperature-sensitive functional monomer, the acrylate monomer, the prodrug monomer, the cross-linking agent and the initiator are mixed and react for 0.5 to 24 hours at 50 to 100 ℃, and the product is separated to remove the unreacted small molecular monomer, so that the intraocular lens material is obtained.
Further, uniformly mixing the temperature-sensitive functional monomer, the acrylate monomer, the prodrug monomer, the cross-linking agent and the initiator under the protection of nitrogen, injecting the mixture into a glass mold, reacting at 50-70 ℃ for 0.5-24 hours, heating to 80-100 ℃, continuing to react for 0.5-24 hours, after the reaction is finished, placing the glass mold in deionized water at 40 ℃ for swelling balance, demolding the polymer material, and removing unreacted micromolecule monomer by replacing the deionized water during the reaction to finally obtain the artificial lens material.
The invention relates to an application of an artificial lens material in the preparation of an artificial lens.
Compared with the prior art, the invention has the beneficial effects that:
the artificial lens material provided by the invention is scientific in composition and reasonable in proportion, and all components play a role together, so that the prepared artificial lens material has good mechanical strength and optical performance, and can effectively reduce complications of ophthalmic surgery.
The human body lens material effectively increases the mechanical strength of the artificial lens material through chemical crosslinking and temperature-sensitive crosslinking; meanwhile, the optical fiber has scientific composition, reasonable proportion and better optical performance. And the addition of the cross-linking agent does not affect the temperature-sensitive effect and the injectability of the composite material while increasing the mechanical strength of the composite material.
The artificial lens material is used as an artificial lens material, and the surgical incision is effectively reduced by an injection implantation mode, so that postoperative complications are avoided.
Meanwhile, the prodrug monomer is contained in the intraocular lens material, and is bonded with the polymer through a covalent bond, so that the intraocular lens material is stable enough in the circulation process, and can reduce the non-specific drug release behavior; the drug loading rate can be improved; the drug loading rate is controllable, and the drug is continuously released without burst release, so that the material can slowly release the anti-inflammatory drug, inhibit the inflammatory reaction of eyes for a long time, and effectively reduce the complications of ophthalmic surgery. In addition, some prodrug monomers have ultraviolet absorption, so that the artificial lens material has the effects of preventing ultraviolet and blue light, is beneficial to eye health of patients and reduces damage to retina.
Drawings
FIG. 1 is a nuclear magnetic spectrum of indomethacin-HEMA.
Figure 2 is a DSC plot of the intraocular lens material of example 1.
Figure 3 is a rheological view of the intraocular lens material of example 1.
Figure 4 is a rheological profile of the intraocular lens material of example 8 without the cross-linking agent.
Detailed Description
The above-mentioned contents of the present invention will be further described in detail by the following specific embodiments of examples. It should be understood that the specific examples described herein are intended to be illustrative only and are not intended to be limiting. Any modification made without departing from the spirit and principle of the present invention and equivalent replacement or improvement made by the common knowledge and conventional means in the field shall be included in the protection scope of the present invention.
Some of the starting materials used in the examples below have the structural formulae shown in the following table:
example 1
This example provides for the preparation of the intraocular lens material of the present invention.
1 preparation of prodrug monomers
Dissolving 130.10mg of anhydrous hydroxyethyl methacrylate and 357.79mg of indometacin in 20ml of anhydrous dichloromethane under stirring to obtain a solution; adding 412.66mg of N, N' -dicyclohexylcarbodiimide and 244.32mg of 4-dimethylaminopyridine into the solution, and stirring the mixture to react for 24 hours at room temperature; detecting reaction by TCL, after the reaction is completed, washing the reaction solution with water, drying, filtering and carrying out rotary distillation; the obtained product is dissolved in a small amount of dichloromethane again, purified by a silica gel chromatographic column and subjected to rotary distillation to obtain the indometacin-HEMA prodrug monomer. The nuclear magnetic spectrum of the obtained prodrug monomer 303.56mg and yield of indomethacin-HEMA of 62.21% is shown in figure 1.
2 selecting a monomer
The monomers and amounts used in this example are shown in the following table:
| species of | Name (R) | Amount (wt%) |
| Temperature-sensitive functional monomer | N-isopropyl acrylamide | 80 |
| Acrylate monomer | Methacrylic |
10 |
| Prodrug monomer | Indometacin-HEMA | 7.5 |
| Crosslinking agent | Ethylene glycol dimethacrylate | 0.5 |
| Initiator | Azobisisobutyronitrile | 2 |
3. Preparation of intraocular lens materials
And (3) uniformly mixing the four monomers and the initiator under the protection of nitrogen, injecting the mixture into a glass mold, heating and polymerizing the mixture for 18 hours in an oven at 60 ℃, then heating the mixture to 90 ℃, and continuing to react for 6 hours. And (3) placing the glass mold in deionized water at 40 ℃ for swelling balance, demolding the polymer material, and removing unreacted small molecular monomers by replacing the deionized water during demolding to finally obtain the temperature-sensitive polymer material capable of being used as the intraocular lens material.
The material has good water solubility below 12 ℃, has good fluidity and can be injected; when the temperature is 37 ℃, the aqueous solution of the polymer is quickly gelatinized, and hydrogel with good mechanical property and optical property is obtained to be used as an artificial lens material; has a refractive index of more than 1.5, a light transmittance of more than 90 percent and a deformation recovery rate of more than 95 percent, and is suitable for being used as an artificial lens material.
As shown in FIG. 2, the intraocular lens material prepared in this example underwent a phase transition at 32 deg.C, and PNIPAAm changed from hydrophilic to hydrophobic to form hydrophobic cross-linking points, resulting in an intraocular lens gel material.
As shown in FIG. 3, the rheological curve of the intraocular lens material prepared in this example shows that the storage modulus (G ') and the loss modulus (G ") increase sharply with increasing temperature, and after 32 degrees, the storage modulus (G') is higher than the loss modulus (G") and is at a higher level, indicating that the intraocular lens material of the present invention undergoes a phase transition at 32 degrees, resulting in a high strength intraocular lens material.
Example 2
This example provides for the preparation of an intraocular lens of the invention.
1 preparation of prodrug monomers
Prepared by the method of example 1 to obtain the indomethacin-HEMA prodrug monomer.
2 selecting a monomer
The monomers and amounts used in this example are shown in the following table:
| species of | Name (R) | Amount (wt%) | |
| Temperature-sensitive functional | Vinyl pyrrolidone | 75 | |
| Acrylate monomer | Methacrylic |
15 | |
| Prodrug monomer | Indometacin-HEMA | 7.5 | |
| Crosslinking agent | Butanediol dimethacrylate | 0.5 | |
| | Dibenzoyl peroxide | 2 |
3. Preparation of intraocular lens materials
And (3) uniformly mixing the four monomers and the initiator under the protection of nitrogen, injecting the mixture into a glass mold, heating and polymerizing the mixture for 18 hours in an oven at 60 ℃, then heating the mixture to 90 ℃, and continuing to react for 6 hours. And (3) placing the glass mold in deionized water at 40 ℃ for swelling balance, demolding the polymer material, and removing unreacted small molecular monomers by replacing the deionized water during demolding to finally obtain the temperature-sensitive polymer material capable of being used as the intraocular lens material.
The material has good water solubility below 12 ℃, has good fluidity and can be injected; when the temperature is 37 ℃, the aqueous solution of the polymer is quickly gelatinized, and hydrogel with good mechanical property and optical property is obtained to be used as an artificial lens material; has a refractive index of more than 1.5, a light transmittance of more than 90 percent and a deformation recovery rate of more than 95 percent, and is suitable for being used as an artificial lens material.
Example 3
This example provides for the preparation of an intraocular lens of the invention.
1 preparation of prodrug monomers
Prepared by the method of example 1 to obtain the indomethacin-HEMA prodrug monomer.
2 selecting a monomer
The monomers and amounts used in this example are shown in the following table:
| species of | Name (R) | Amount (wt%) |
| Temperature-sensitive functional monomer | Methacrylic acid dimethylamine ethyl ester | 85 |
| Acrylate monomer | Methacrylic |
5 |
| Prodrug monomer | Indometacin-HEMA | 7.5 |
| Crosslinking agent | Acrylic acid hexanediol ester | 0.8 |
| Initiator | Ammonium peroxodisulfate | 1.7 |
3. Preparation of intraocular lens materials
The four monomers and initiator were dissolved in 5ml of acetic acid under nitrogen protection: the mixture was poured into a glass mold with a ratio of 1:1, heated in an oven at 60 ℃ for polymerization for 18 hours, and then heated to 90 ℃ for further reaction for 6 hours. And (3) placing the glass mold in deionized water at 40 ℃ for swelling balance, demolding the polymer material, and removing unreacted small molecular monomers by replacing the deionized water during demolding to finally obtain the temperature-sensitive polymer material capable of being used as the intraocular lens material.
The material has good water solubility below 12 ℃, good fluidity and can be injected; when the temperature is 37 ℃, the aqueous solution of the polymer is quickly gelatinized, and hydrogel with good mechanical property and optical property is obtained to be used as an artificial lens material; has a refractive index of more than 1.5, a light transmittance of more than 90 percent and a deformation recovery rate of more than 95 percent, and is suitable for being used as an artificial lens material.
Example 4
This example provides for the preparation of the intraocular lens material of the present invention.
1 preparation of prodrug monomers
Dissolving 130.10mg of anhydrous hydroxyethyl methacrylate and 370.38mg of levofloxacin into 20ml of anhydrous dichloromethane under the condition of stirring to obtain a solution; adding 412.66mg of N, N' -dicyclohexylcarbodiimide and 244 mg and 32mg of 4-dimethylaminopyridine into the solution, and stirring the mixture at room temperature for reacting for 24 hours; detecting reaction by TCL, after the reaction is completed, washing the reaction solution with water, drying, filtering and carrying out rotary distillation; and dissolving the obtained product in a small amount of dichloromethane again, purifying by using a silica gel chromatographic column, and performing rotary distillation to obtain the levofloxacin-HEMA prodrug monomer. The prodrug monomer was obtained at 322.45mg, yield 64.43%.
2 selecting a monomer
The monomers and amounts used in this example are shown in the following table:
| species of | Name (R) | Amount (wt%) | |
| Temperature-sensitive functional monomer | N-isopropyl acrylamide | 80 | |
| Acrylate monomer | Methacrylic |
10 | |
| Prodrug monomer | levofloxacin-HEMA | 7.5 | |
| Crosslinking agent | Ethylene glycol dimethacrylate | 0.5 | |
| | Azobisisobutyronitrile | 2 |
3. Preparation of intraocular lens materials
And (3) uniformly mixing the four monomers and the initiator under the protection of nitrogen, injecting the mixture into a glass mold, heating and polymerizing the mixture for 18 hours in an oven at 60 ℃, then heating the mixture to 90 ℃, and continuing to react for 6 hours. And (3) placing the glass mold in deionized water at 40 ℃ for swelling balance, demolding the polymer material, and removing unreacted small molecular monomers by replacing the deionized water during demolding to finally obtain the temperature-sensitive polymer material capable of being used as the intraocular lens material.
The material has good water solubility below 12 ℃, good fluidity and can be injected; when the temperature is 37 ℃, the aqueous solution of the polymer is quickly gelatinized, and hydrogel with good mechanical property and optical property is obtained to be used as an artificial lens material; has a refractive index of more than 1.5, a light transmittance of more than 90 percent and a deformation recovery rate of more than 95 percent, and is suitable for being used as an artificial lens material.
Example 5
This example provides for the preparation of the intraocular lens material of the present invention.
1 preparation of prodrug monomers
Prepared by the method of example 4 to obtain levofloxacin-HEMA prodrug monomer.
2 selecting a monomer
The monomers and amounts used in this example are shown in the following table:
| species of | Name (R) | Amount (wt%) | |
| Temperature-sensitive functional | Vinyl pyrrolidone | 75 | |
| Acrylate monomer | Methacrylic |
15 | |
| Prodrug monomer | levofloxacin-HEMA | 7.5 | |
| Crosslinking agent | Butanediol dimethacrylate | 1 | |
| Initiator | Dibenzoyl peroxide | 1.5 |
3. Preparation of intraocular lens materials
Dissolving the four monomers and the initiator in 5ml of methanol under the protection of nitrogen, uniformly mixing, injecting into a glass mold, heating and polymerizing for 18 hours at 60 ℃ in an oven, then heating to 90 ℃, and continuing to react for 6 hours. And (3) placing the glass mold in deionized water at 40 ℃ for swelling balance, demolding the polymer material, and removing unreacted small molecular monomers by replacing the deionized water during demolding to finally obtain the temperature-sensitive polymer material capable of being used as the intraocular lens material.
The material has good water solubility below 12 ℃, good fluidity and can be injected; when the temperature is 37 ℃, the aqueous solution of the polymer is quickly gelatinized, and hydrogel with good mechanical property and optical property is obtained to be used as an artificial lens material; has a refractive index of more than 1.5, a light transmittance of more than 90 percent and a deformation recovery rate of more than 95 percent, and is suitable for being used as an artificial lens material.
Example 6
This example provides for the preparation of the intraocular lens material of the present invention.
1 preparation of prodrug monomers
Prepared by the method of example 4 to obtain levofloxacin-HEMA prodrug monomer.
2 selecting a monomer
The monomers and amounts used in this example are shown in the following table:
| species of | Name (R) | Amount (wt%) |
| Temperature-sensitive functional monomer | Methacrylic acid |
75 |
| Acrylate monomer | Methacrylic |
15 |
| Prodrug monomer | levofloxacin-HEMA | 7.5 |
| Crosslinking agent | Acrylic |
1 |
| Initiator | Ammonium peroxodisulfate | 1.5 |
3. Preparation of intraocular lens materials
The four monomers and initiator were dissolved in 5ml of methanol under nitrogen protection: and (3) uniformly mixing the water-1: 1 solution, injecting the mixture into a glass mold, heating and polymerizing the mixture for 18 hours in an oven at 60 ℃, then raising the temperature to 90 ℃, and continuing to react for 6 hours. And (3) placing the glass mold in deionized water at 40 ℃ for swelling balance, demolding the polymer material, and removing unreacted small molecular monomers by replacing the deionized water during demolding to finally obtain the temperature-sensitive polymer material capable of being used as the intraocular lens material.
The material has good water solubility below 12 ℃, good fluidity and can be injected; when the temperature is 37 ℃, the aqueous solution of the polymer is quickly gelatinized, and hydrogel with good mechanical property and optical property is obtained to be used as an artificial lens material; has a refractive index of more than 1.5, a light transmittance of more than 90 percent and a deformation recovery rate of more than 95 percent, and is suitable for being used as an artificial lens material.
Example 7
This example provides for the preparation of the intraocular lens material of the present invention.
1 preparation of prodrug monomers
Dissolving 130.10mg of anhydrous hydroxyethyl methacrylate and 296.15mg of diclofenac in 20ml of anhydrous dichloromethane under stirring to obtain a solution; adding 412.66mg of N, N' -dicyclohexylcarbodiimide and 244.32mg of 4-dimethylaminopyridine into the solution, and stirring the mixture to react for 24 hours at room temperature; detecting reaction by TCL, after the reaction is completed, washing the reaction solution with water, drying, filtering and carrying out rotary distillation; and dissolving the obtained product in a small amount of dichloromethane again, purifying by using a silica gel chromatographic column, and performing rotary distillation to obtain the diclofenac-HEMA prodrug monomer. The prodrug monomer was obtained at 271.91mg, yield 63.79%.
2 selecting a monomer
The monomers and amounts used in this example are shown in the following table:
3. preparation of intraocular lens materials
And (3) uniformly mixing the four monomers and the initiator under the protection of nitrogen, injecting the mixture into a glass mold, polymerizing the mixture in an oven at 60 ℃, and continuously reacting for 6 hours. And (3) placing the glass mold in deionized water at 40 ℃ for swelling balance, demolding the polymer material, and removing unreacted small molecular monomers by replacing the deionized water during demolding to finally obtain the temperature-sensitive polymer material capable of being used as the intraocular lens material.
The material has good water solubility below 12 ℃, good fluidity and can be injected; when the temperature is 37 ℃, the aqueous solution of the polymer is quickly gelatinized, and hydrogel with good mechanical property and optical property is obtained to be used as an artificial lens material; has a refractive index of more than 1.5, a light transmittance of more than 90 percent and a deformation recovery rate of more than 95 percent, and is suitable for being used as an artificial lens material.
Example 8
This example is a comparative example, and compared to example 1, this example has no crosslinker added, and the remaining conditions are the same.
As shown in FIG. 4, the rheological curve of the intraocular lens material prepared without adding the crosslinking agent in this example shows that the storage modulus (G ') and the loss modulus (G') increase sharply with increasing temperature, and the intraocular lens is produced by phase transition after 32 degrees, but the storage modulus (G ') and the loss modulus (G') are at a lower level after the phase transition.
The foregoing is merely a preferred embodiment of this invention, which is intended to be illustrative, not limiting; it will be understood by those skilled in the art that many changes, modifications and equivalents may be made therein without departing from the scope of the invention as defined in the claims, but the scope of the invention is to be determined accordingly.
Claims (7)
1. The high-strength intraocular lens material capable of being injected and slowly releasing drugs is characterized in that the intraocular lens material is formed by polymerizing four monomers, wherein the four monomers are a temperature-sensitive functional monomer, an acrylate monomer, a prodrug monomer and a cross-linking agent respectively; the prodrug monomer is a derivative of an anti-inflammatory drug with a polymerizable double bond;
the sum of the total mass percentage of the four monomers is 100%, the content of the temperature-sensitive functional monomer is 20-45 wt%, the content of the acrylate monomer is 20-45 wt%, the content of the prodrug monomer is 10-35 wt%, and the content of the cross-linking agent is 0.1-5 wt%.
2. A high strength intraocular lens material capable of both injection and sustained release of a drug according to claim 1 wherein the temperature sensitive functional monomer is selected from one of N-isopropylacrylamide, vinyl pyrrolidone, dimethylaminoethyl methacrylate.
3. A high strength injectable slow release drug intraocular lens material of claim 2 wherein the anti-inflammatory drug is selected from one of indomethacin, levofloxacin, diclofenac, ribavirin, dexamethasone, ganciclovir, chloramphenicol, norfloxacin, prednisone, acyclovir, lanosterol.
4. A high strength injectable drug-releasing intraocular lens material as in claim 1 wherein the cross-linking agent is one of ethylene glycol dimethacrylate, or butylene glycol dimethacrylate, or hexanediol acrylate, or diethylene glycol diacrylate.
5. The method for preparing a high-strength intraocular lens material capable of injecting and slowly releasing drugs according to any one of claims 1 to 4, characterized in that the temperature-sensitive functional monomer, acrylate monomer, prodrug monomer, cross-linking agent and initiator are mixed and reacted at 50-100 ℃ for 0.5-24 hours, and the product is separated to remove unreacted small molecule monomer, thus obtaining the intraocular lens material.
6. The preparation method of the high-strength intraocular lens material capable of injecting and slowly releasing drugs according to claim 5, characterized in that the temperature-sensitive functional monomer, the acrylate monomer, the prodrug monomer, the cross-linking agent and the initiator are mixed uniformly under the protection of nitrogen, and then injected into a glass mold, reacted at 50-70 ℃ for 0.5-24 hours, then heated to 80-100 ℃, and continuously reacted for 0.5-24 hours, after the reaction is finished, the glass mold is placed in deionized water of 40 ℃ for swelling balance, the polymer material is demolded, and during the period, the unreacted small molecular monomer is removed by replacing the deionized water, and finally the intraocular lens material is obtained.
7. Use of an intraocular lens material according to any one of claims 1 to 4 in the manufacture of an intraocular lens.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1201824C (en) * | 1998-03-16 | 2005-05-18 | 法玛西雅厄普约翰格罗宁根有限公司 | Method and materials for producing intracular lenses |
| CN102231989A (en) * | 2008-07-21 | 2011-11-02 | 爱尔康公司 | Ophthalmic device having therapeutic agent delivery capability and method of forming same |
| CN106632833A (en) * | 2016-10-31 | 2017-05-10 | 四川大学 | Injectable temperature-sensitive hydrogel artificial lens material having cell membrane biomimetic property and preparation method thereof |
| KR20170116811A (en) * | 2016-04-12 | 2017-10-20 | 아주대학교산학협력단 | Injectable double network hydrogels and biomedical use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1201824C (en) * | 1998-03-16 | 2005-05-18 | 法玛西雅厄普约翰格罗宁根有限公司 | Method and materials for producing intracular lenses |
| CN102231989A (en) * | 2008-07-21 | 2011-11-02 | 爱尔康公司 | Ophthalmic device having therapeutic agent delivery capability and method of forming same |
| KR20170116811A (en) * | 2016-04-12 | 2017-10-20 | 아주대학교산학협력단 | Injectable double network hydrogels and biomedical use thereof |
| CN106632833A (en) * | 2016-10-31 | 2017-05-10 | 四川大学 | Injectable temperature-sensitive hydrogel artificial lens material having cell membrane biomimetic property and preparation method thereof |
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