CN112415773A - Medicine-carrying contact lens for promoting corneal epithelium injury repair and preparation method thereof - Google Patents
Medicine-carrying contact lens for promoting corneal epithelium injury repair and preparation method thereof Download PDFInfo
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- CN112415773A CN112415773A CN202011411129.3A CN202011411129A CN112415773A CN 112415773 A CN112415773 A CN 112415773A CN 202011411129 A CN202011411129 A CN 202011411129A CN 112415773 A CN112415773 A CN 112415773A
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- contact lens
- drug
- gelatin
- loaded contact
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- 230000001737 promoting effect Effects 0.000 title claims abstract description 9
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Images
Classifications
-
- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
- G02C7/00—Optical parts
- G02C7/02—Lenses; Lens systems ; Methods of designing lenses
- G02C7/04—Contact lenses for the eyes
- G02C7/049—Contact lenses having special fitting or structural features achieved by special materials or material structures
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/045—Gelatin
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
- G02C7/00—Optical parts
- G02C7/02—Lenses; Lens systems ; Methods of designing lenses
- G02C7/021—Lenses; Lens systems ; Methods of designing lenses with pattern for identification or with cosmetic or therapeutic effects
-
- 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
- A61L2300/20—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
Abstract
The invention provides a drug-loaded contact lens for promoting corneal epithelial injury repair and a preparation method thereof. The invention provides a medicine-carrying contact lens for promoting corneal epithelial injury repair, which is simple to manufacture, has good biocompatibility, can carry out medicine slow release for a long time and better treats eye diseases. Compared with the traditional eye drops, the eye drop can slowly release the medicine for a long time, greatly overcomes the defects of high concentration of partial ophthalmic medicines and great side effect, and can effectively treat eye diseases.
Description
Technical Field
The invention belongs to the technical field of spectacle lenses, and particularly relates to a drug-loaded contact lens for promoting corneal epithelium injury repair and a preparation method thereof.
Background
The cornea plays an important role in the refraction and barrier protection of the eye, while the corneal epithelium is one of the important biological barriers of the eye and can resist attack of chemicals, microorganisms and the like to a certain extent. Damage to the corneal epithelium can easily cause serious complications such as eye infection, ulcer, perforation, scar and the like if the treatment is not timely carried out. At present, most of methods for treating corneal epithelial injury are eye drops or eye ointment, and the bioavailability of the medicine is reduced due to the complex structure of the ocular surface and higher resistance to foreign substance delivery. Reflex tearing and blinking, nasolacrimal duct drainage, relative impermeability of corneal epithelium, nonproductive absorption, metabolic degradation result in short residence time and low absorption of the drug in the eye. In addition, most of the existing therapeutic drugs are chemical agents, the higher therapeutic concentration is high, and the intermittent administration mode can cause the severe fluctuation of the drug level in the eyes and even can cause the side effects of the eyes and the whole body. Therefore, there is a need to develop safe and effective drug delivery means.
With the development of materials technology, contact lenses have been studied to various degrees as a new ophthalmic drug delivery vehicle. Gelatin as a biomaterial is widely used in the pharmaceutical field and the biomedical engineering field due to its excellent biocompatibility and good degradation property. With the deep understanding of natural products, many natural products having various biological activities and higher medicinal values are continuously studied in the field of ophthalmology. Rutin, as a natural product, is a polyphenol flavone, widely exists in the plant world, and has good biocompatibility and extremely high bioactivity. The antioxidant, anti-inflammatory and anti-fibrosis activities of the compound have proved to play an important role in the treatment of eye diseases such as keratoconus, Graves eye disease, conjunctivitis, cataract, xerophthalmia, retinopathy and the like. The contact lens is taken as a carrier, and the biological material gelatin and the natural product rutin are added to realize the slow release of the long-acting medicament, thereby bringing a new treatment means for ophthalmic diseases and having important clinical significance.
Disclosure of Invention
The invention aims to provide a medicine-carrying contact lens for promoting corneal epithelial injury repair and a preparation method thereof, which can be used for treating related eye diseases and relieving eye symptoms so as to make up for the defects of the prior art.
The drug-loaded contact lens for promoting corneal epithelium injury repair is prepared by integrating rutin into acrylate functionalized gelatin;
a specific method is characterized in that the flavonoid compound rutin, hydroxyethyl methacrylate, methacrylic acid, a cross-linking agent and a thermal initiator are added into an acrylate functionalized gelatin solution, mixed and ultrasonically homogenized, and then the mixture is injected into a contact lens mold to prepare the medical contact lens.
As a specific description of the embodiment, the crosslinking agent is ethylene glycol dimethacrylate; the thermal initiator is azobisisobutyronitrile;
more specifically, the method comprises the following steps:
1) adding acrylate functionalized gelatin into distilled water, heating to fully dissolve the acrylate functionalized gelatin to prepare a gelatin water solution with the mass concentration of 16.7%;
2) adding rutin (0.3-1.3% w/w), hydroxyethyl methacrylate (50.84-50.98% w/w), methacrylic acid (19.22-19.28% w/w) and ethylene glycol dimethacrylate (0.45-0.46% w/w) with different amounts into the gelatin water solution, and carrying out ultrasonic mixing at normal temperature to uniformly mix the rutin and the hydroxyethyl methacrylate;
3) adding sodium carboxymethylcellulose (0.145% -0.146%, w/w), N-hydroxysuccinimide (0.02% -0.03%, w/w) and thermal initiator azobisisobutyronitrile (0.145% -0.146%, w/w) into the mixed solution obtained in the step 3), and ultrasonically mixing the mixed system at normal temperature to be uniform;
4) adding the mixed system of the step 4) into a contact lens mold; placing the mixture in a water bath kettle at 65 ℃ for reaction for 30 hours, and then boiling the mixture in water to remove unreacted monomers; cooling and then finishing the preparation of the contact lens
The acrylate functionalized gelatin is prepared by adding gelatin into water, fully stirring until the gelatin is completely dissolved, adding acrylic anhydride for overnight reaction at 50 ℃, dialyzing, and freeze-drying the dialyzate.
The invention provides a medicine-carrying contact lens for promoting corneal epithelial injury repair and a preparation method thereof. Compared with the traditional eye drops, the eye drop can slowly release the medicine for a long time, greatly overcomes the defects of high concentration of partial ophthalmic medicines and great side effect, and can effectively treat eye diseases.
Drawings
FIG. 1A) is a graph of the appearance of different drug-loaded contact lenses prepared in example 1 and containing different amounts of drug to promote repair of corneal epithelial damage; B) transparency test images of drug-loaded contact lenses prepared in example 1 at different drug loadings to promote repair of corneal epithelial damage.
Fig. 2 is a drug release profile of the drug-loaded contact lens prepared in example 1 with different drug contents to promote corneal epithelial injury repair.
FIG. 3 is a graph of an animal epithelial damage repair experiment for the contact lens prepared in example 1.
Detailed Description
The present invention will be described in detail below with reference to examples and the accompanying drawings.
Example 1
1) Adding 45ml of water into 5g of gelatin, fully stirring at 50 ℃ until the gelatin is completely dissolved, adding 5ml of acrylic anhydride, reacting at 50 ℃ overnight, dialyzing for 6 days, and freeze-drying to prepare the acrylate functionalized gelatin;
2) adding 5mg of acrylate functionalized gelatin into 300 mul of distilled water, and heating in a water bath at 50 ℃ to fully dissolve the acrylate functionalized gelatin to obtain a gelatin water solution;
3) adding 1-4mg of natural product flavonoid compound rutin and hydrogel mixture (490. mu.l of hydroxyethyl methacrylate: 210 mul of methacrylic acid, 70:30) and 4.5 mul of ethylene glycol dimethacrylate are mixed evenly by ultrasonic treatment for 3-5min at normal temperature;
4) adding 1.5mg of sodium carboxymethylcellulose, 0.3mg of N-hydroxysuccinimide and 1.5mg of thermal initiator azobisisobutyronitrile into the mixed solution obtained in the step 3), and carrying out ultrasonic treatment on the mixed system at normal temperature for 2-3min to uniformly mix the mixed solution;
5) adding the mixed system of the step 4) into a contact lens mold; placing in a 65 deg.C water bath kettle for reaction for 30h, boiling in water for 5min to remove monomer;
6) the contact lens is carefully removed from the mold.
Example 2
1) Adding 45ml of water into 5g of gelatin, fully stirring at 50 ℃ until the gelatin is completely dissolved, adding 5ml of acrylic anhydride, reacting at 50 ℃ overnight, dialyzing for 6 days, and freeze-drying to prepare the acrylate functionalized gelatin;
2) adding 5mg of acrylate functionalized gelatin into 300 mul of distilled water, and heating in a water bath at 50 ℃ to fully dissolve the acrylate functionalized gelatin to obtain a gelatin water solution;
3) adding 1-4mg of natural product flavonoid compound rutin and hydrogel mixture (490. mu.l of hydroxyethyl methacrylate: 210 mul of methacrylic acid, 70:30) and 4.5 mul of ethylene glycol dimethacrylate are mixed evenly by ultrasonic treatment for 3-5min at normal temperature;
4) adding 1.5mg of thermal initiator azobisisobutyronitrile into the mixed solution obtained in the step 3), and carrying out ultrasonic treatment on the mixed system at normal temperature for 2-3min to uniformly mix the mixed system;
5) adding the mixed system of the step 4) into a contact lens mold; placing in a 65 deg.C water bath kettle for reaction for 30h, boiling in water for 5min to remove monomer;
6) the contact lens is carefully removed from the mold.
The prepared contact lens is subjected to material characterization detection, swelling detection, transparency detection, cytotoxicity detection, drug slow release and in-vivo pharmacodynamic detection, and partial detection results of the product are as follows:
1) transparency
The transparency of the contact lens was recorded and evaluated by placing the contact lens on a piece of white paper on which the black letter "a" was written (fig. 1A). The light transmittance of the contact lens was measured at 50nm intervals in the wavelength range of 250-800nm using a UV-visible spectrophotometer (SpectraMax M2, Molecular Devices, MD, USA) (FIG. 1B). The gelatin has no influence on the transparency of the contact lens.
2) Sustained drug release
The contact lens with the drug was soaked in 4ml of deionized water and placed in a shaker incubator at 35 ℃ and 100 rpm. At predetermined time intervals, 1mL of the modified release solution was replaced with fresh deionized water. Measuring rutin content at 254nm wavelength. And (3) drawing a curve of the accumulated release amount of rutin along with time, and evaluating the release amount curve of rutin (figure 2). The detection shows that the release amount of rutin is increased along with the increase of the drug-loading rate of the contact lens, and the contact lens with different drug-loading rates can continuously and slowly release the drug for 36 days.
3) Study of pharmacodynamics
New Zealand white rabbits were used as study subjects, the right eye as a control group, and the left eye as an experimental group, and contact lenses were worn for 6 hours every day for 4 consecutive days. Rabbit eye health was observed using a slit-lamp microscope and photographed daily (FIG. 3B).
The repairing effect of rutin on corneal epithelial injury is observed. The right eye is the control group and the left eye is the experimental group. Both groups were anesthetized, a 9mm trephine was used to imprint a mark on the center of the cornea as the surgical field, and an electric epithelium scraper was used to scrape the corneal epithelium from the surgical field. Two groups were administered with anti-inflammatory drugs post-operatively, with the experimental group having a contact lens and the control group having no contact lens. At predetermined time intervals, two groups of rabbits were evaluated for epithelial repair by staining with sodium fluorescein and recorded by photography (fig. 3A).
The detection shows that the contact lens has better biocompatibility in animals, and the epithelial repair condition of an experimental group in a damage repair experiment is obviously better than that of a control group, which indicates that the contact lens has better clinical treatment effect.
Claims (8)
1. A drug-loaded contact lens for promoting corneal epithelial injury repair is characterized in that the drug-loaded contact lens is prepared by integrating rutin into acrylate functionalized gelatin.
2. The drug-loaded contact lens of claim 1, wherein the preparation method comprises adding rutin, hydroxyethyl methacrylate, methacrylic acid, a cross-linking agent and a thermal initiator into an acrylate functionalized gelatin solution, mixing and ultrasonically homogenizing, and then injecting the mixture into a contact lens mold.
3. The drug-loaded contact lens of claim 2, wherein the cross-linking agent is ethylene glycol dimethacrylate.
4. The drug-loaded contact lens of claim 2, wherein the thermal initiator is azobisisobutyronitrile.
5. The drug-loaded contact lens of claim 2, wherein the method of making the contact lens comprises the steps of:
1) adding acrylate functionalized gelatin into distilled water, heating to fully dissolve the acrylate functionalized gelatin to prepare a gelatin water solution with the mass concentration of 16.7%;
2) adding reed, hydroxyethyl methacrylate, methacrylic acid and ethylene glycol dimethacrylate into the gelatin water solution, and performing ultrasonic treatment at normal temperature to uniformly mix the reed, the hydroxyethyl methacrylate, the methacrylic acid and the ethylene glycol dimethacrylate;
3) adding sodium carboxymethylcellulose, N-hydroxysuccinimide and thermal initiator azobisisobutyronitrile into the mixed solution obtained in the step 3), and performing ultrasonic treatment on the mixed system at normal temperature to uniformly mix the mixed solution;
4) adding the mixed system of the step 4) into a contact lens mold; placing the mixture in a water bath kettle at 65 ℃ for reaction for 30 hours, and then boiling the mixture in water to remove unreacted monomers; and cooling to complete the preparation of the contact lens.
6. The drug-loaded contact lens of claim 5, wherein the acrylate functionalized gelatin in 1) is prepared by adding gelatin into water, fully stirring until the gelatin is completely dissolved, adding acrylic anhydride, reacting overnight at 50 ℃, dialyzing, and freeze-drying the dialyzate.
7. The drug-loaded contact lens of claim 5, wherein the concentration by mass of rutin in 2) is 0.3% -1.3%, the concentration by mass of hydroxyethyl methacrylate is 50.84% -50.98%, the concentration by mass of methacrylic acid is 19.22% -19.28%, and the concentration by mass of ethylene glycol dimethacrylate is 0.45% -0.46%.
8. The drug-loaded contact lens of claim 5, wherein in step 3), the mass concentration of sodium carboxymethylcellulose is 0.145% -0.146%, the mass concentration of N-hydroxysuccinimide is 0.02% -0.03%, and the mass concentration of the thermal initiator azobisisobutyronitrile is 0.145% -0.146%.
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