CN113941298B - Preparation method of eye photothermal treatment carrier - Google Patents
Preparation method of eye photothermal treatment carrier Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 238000011282 treatment Methods 0.000 title abstract description 22
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- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims abstract description 33
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/0052—Preparation of gels
- B01J13/0065—Preparation of gels containing an organic phase
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
- A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/0625—Warming the body, e.g. hyperthermia treatment
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
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- A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
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Abstract
The invention discloses a preparation method of an eye photothermal treatment carrier. According to the invention, hydrogel is used as a carrier, and silver-containing graphene oxide with photoresponsivity is uniformly dispersed in the hydrogel, so that the hydrogel has certain photo-thermal conversion performance. The invention has the advantages that: on one hand, the medicine can stay in the eyes for a certain time to better play a role; on the other hand, the hydrogel can rapidly respond to near infrared light and can maintain the temperature within the range required by photothermal treatment, and can effectively induce conjunctival fibroblast apoptosis under the irradiation of near infrared light, thereby achieving the purpose of long-term maintenance of the postoperative filtering bleb of glaucoma.
Description
Technical Field
The invention belongs to the technical field of biological materials, and particularly relates to a preparation method of an eye photothermal treatment carrier.
Background
Glaucoma is the most-ranked irreversible blinding eye disease at present, the main clinical characteristics of the glaucoma are mainly pathological intraocular pressure elevation, and intraocular pressure reduction is the only treatment means which is verified by multi-center clinical experiments and has definite curative effect. When the effect of the medicine and laser treatment is poor, the filtration operation treatment is considered. At present, compound trabeculectomy is still the mainstream in various filtering operations, but the success rate of the operation is not satisfactory, and the main reason is that the incision can be excessively healed after the operation. Therefore, an anti-scarring drug is needed to regulate the wound healing process during or after surgery to prevent the excessive proliferation of fibroblasts in the filtration zone; and the application of anti-scar medicines can also lead to the increase of the incidence rate of adverse reactions after operation. To date, no way or medicine can perfectly balance the relationship among aqueous humor filtration, postoperative wound healing and reduction of postoperative complication occurrence. And the development of rapid nanomaterial technology in recent years provides a new approach and hope for solving the difficult problem.
Graphene is a nanomaterial of a monolayer two-dimensional honeycomb lattice structure with hybridized connection of carbon atoms. Graphene oxide is the most predominant derivative thereof, and not only has a two-dimensional planar structure similar to graphene, but also a large number of oxygen-containing functional groups distributed thereon gives it excellent hydrophilicity and possibility of being surface-modified. In recent years, graphene has been used in medical field to realize synergistic chemotherapy-photothermal therapy of tumor by utilizing its excellent photothermal conversion performance and strong drug loading capability. The photothermal therapy realized by near infrared laser can be controllably implemented at specific time and specific position, and has high flexibility and safety.
Based on the above-mentioned state of the art, there is a strong need for a more controllable, intelligent and safer method for regulating the healing process of wounds after glaucoma surgery.
Disclosure of Invention
Aiming at the problems in the background technology, the invention takes New Zealand white rabbits as early-stage test objects, develops an eye photothermal therapy carrier, and explores the situation that the synergistic chemotherapy-photothermal therapy is applied to the anti-glaucoma filtration postoperative scarring.
A first object of the present invention is to create an ocular photothermal treatment vehicle.
The second aim of the invention is to provide a controllable, intelligent and safe method for regulating and controlling the scar formation degree of the wound after glaucoma filtration operation so as to improve the success rate of the operation.
In order to achieve the above purpose, the invention is realized by the following technical scheme:
the preparation method of the eye photothermal treatment carrier comprises the following steps:
A. preparation of silver-containing graphene oxide:
a) Sequentially adding graphite powder, potassium persulfate and phosphorus pentoxide into concentrated sulfuric acid, stirring at 50-100 ℃ for 1-5 hours, and then washing with ultrapure water until the pH of the solution is 6-8;
b) Slowly adding the solution obtained in the step A-a) and potassium permanganate into concentrated sulfuric acid, heating to 20-40 ℃ and stirring for 4-8 hours, and then diluting with ultrapure water and stirring;
c) Adding 10% -40% (w/v) hydrogen peroxide into the solution obtained in the step A-b), standing for 8-14 hours, removing supernatant to obtain precipitate, and washing with hydrochloric acid and ultrapure water until the pH of the solution is 6-8;
d) Dropwise adding the solution obtained in the step A-c) into a silver nitrate solution, stirring for 20-60 minutes, heating the solution to 50-100 ℃, dropwise adding 1-10mol/L sodium hydroxide to react for 1-5 hours, cooling the reaction solution to room temperature, and washing with ultrapure water until the pH value is 6-8 to obtain silver-containing graphene oxide;
B. preparation of hydrogels:
a) Preparing 10% -15% (w/v) polyvinyl alcohol solution, and stirring at 70-100 ℃ for 1-5 hours to make the solution in a homogeneous state;
b) Mixing the silver-containing graphene oxide prepared in the step A with the polyvinyl alcohol solution prepared in the step B-a), and stirring for 10-30 minutes to obtain a homogeneous solution;
c) Adding 5-fluorouracil with the concentration of 20-30mg/mL into the homogeneous solution obtained in the step B-B), stirring for 5-30 minutes, freezing the solution at-20 ℃ and thawing and circulating at 37 ℃ for three times, and refrigerating the obtained product at 4 ℃.
Further, the raw materials in the step A are proportioned according to parts by weight: 0.5-2.0 parts of graphite powder, 0.5-3.0 parts of potassium persulfate, 0.5-3.0 parts of phosphorus pentoxide and 1.0-8.0 parts of potassium permanganate.
Further, the solution ratios in the steps A-d) are as follows according to the volume parts: 5-15 parts of the solution obtained in the step A-c), 5-15 parts of silver nitrate solution and 2-3 parts of sodium hydroxide.
Further, the preparation method of the silver nitrate solution comprises the steps of dissolving 0.001-0.01g of silver nitrate in 5-15mL of ultrapure water; the concentration of the solution obtained in the step A-c) is regulated to be 0.5-1.5mg/mL before the solution is dripped into the silver nitrate solution.
Further, the volume fraction of the hydrochloric acid in the step A-c) is 1 (5-20).
Further, the solution in the step B is prepared from the following components in parts by volume: 0.1-1 part of silver-containing graphene oxide, 5-10 parts of polyvinyl alcohol solution and 1-5 parts of 5-fluorouracil.
Further, the freezing time in the step B-c) is 5-15 hours, and the thawing time is 15-45 minutes.
Further, the silver-containing graphene oxide obtained in the step A is uniformly dispersed in the hydrogel patch in the step B, so that the silver-containing graphene oxide has a certain photo-thermal conversion effect, and the aim of photo-thermal treatment is fulfilled.
Further, 5-fluorouracil is uniformly dispersed in the hydrogel patch in the step B, so that the hydrogel patch has a certain drug release process to achieve the purpose of eye treatment.
Further, the ophthalmic photothermal treatment vector is applied to treat glaucoma-related ophthalmic diseases.
The eye photothermal treatment carrier prepared by the invention has good biocompatibility, and can enable the medicine to stay in the eyes for a certain time to play a role; meanwhile, the kit can rapidly respond to near infrared light, can maintain the temperature within a range required by photothermal treatment, and can effectively induce conjunctival fibroblast apoptosis under the irradiation of near infrared light. After the hydrogel is implanted, the survival rate of the filtering bleb after rabbit eye operation is obviously improved.
Compared with the prior art, the invention has the beneficial effects that:
1. the eye photothermal treatment carrier synthesized by the invention can prolong the retention time of the medicine in eyes.
2. The eye photothermal treatment carrier synthesized by the invention has good photothermal conversion capability and can maintain the temperature within the required range of photothermal treatment.
3. The eye photothermal treatment carrier synthesized by the invention can effectively weaken scar after glaucoma filtration operation under near infrared light irradiation.
Drawings
Fig. 1 is a morphological characterization of a silver-containing graphene oxide hydrogel.
Fig. 2 is a measurement of the photo-thermal efficiency of a silver-containing graphene oxide hydrogel.
Fig. 3 is a measurement of the release efficiency of a drug-loaded silver-containing graphene oxide hydrogel.
Fig. 4 is an evaluation of the anti-scarring effect of a drug-loaded silver-containing graphene oxide hydrogel applied after glaucoma filtration.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be clearly and completely described in the following examples. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Example 1: morphology characterization of silver-containing graphene oxide hydrogels
A. Preparation of silver-containing graphene oxide:
(a) Under ice water bath conditions, 1.5g of graphite powder, 2.5g of potassium persulfate and 2.5g of phosphorus pentoxide are sequentially added into 24mL of concentrated sulfuric acid, and stirred at 80 ℃ for 4.5 hours;
(b) Washing the solution prepared in A-a with ultrapure water until the pH is 7;
(c) Slowly adding the solution prepared in the step A-b and 7.5g of potassium permanganate into 60mL of concentrated sulfuric acid under certain conditions, heating to 35 ℃ and stirring for 6 hours;
(d) The solution prepared in A-c is diluted with 250mL of ultrapure water and then stirred for 2 hours, and then diluted with 300mL of ultrapure water;
(e) 10mL of 30% (w/v) hydrogen peroxide was added to the solution prepared in A-d, and after 12 hours of standing, the supernatant was decanted;
(f) Washing the precipitate obtained in A-e twice with 500mL of 1:10 hydrochloric acid prepared, and then washing with a large amount of ultrapure water until the pH reaches 7;
(g) Weighing 0.0088g of silver nitrate, dissolving in 10mL of ultrapure water, dropwise adding 1mg/mL of the solution obtained in the steps A-f and stirring for 30 minutes;
(h) Heating the solution prepared in the step A-g to 80 ℃, dropwise adding 8mol/L sodium hydroxide 2.2mL for reaction for 2 hours, and cooling to room temperature;
(i) Washing the solution prepared in the step A-h by ultrapure water until the pH value is 7, and obtaining the silver-containing graphene oxide.
B. Preparation of hydrogels
(a) Firstly, preparing 14% (w/v) polyvinyl alcohol solution and stirring for 4 hours at 90 ℃ to obtain a homogeneous state;
(b) Taking 0.8mL of the silver-containing graphene oxide prepared in the step A, mixing with 6mL of 14% (w/v) polyvinyl alcohol prepared in the step B-a, and stirring for 15 minutes to obtain a homogeneous solution;
(c) Taking 0.1mL of the solution prepared in the step B-B into a 96-well plate;
(d) Freezing the flat plate obtained in the step B-c in a refrigerator at the temperature of minus 20 ℃ for 12 hours, and then thawing the flat plate in a constant temperature cabinet at the temperature of 37 ℃ for 30 minutes;
(e) Freezing the flat plate obtained in the step B-d in a refrigerator at the temperature of minus 20 ℃ for 12 hours, and then thawing the flat plate in a constant temperature cabinet at the temperature of 37 ℃ for 30 minutes;
(f) The plates obtained in B-e were frozen in a refrigerator at-20℃for 12 hours, and then thawed in a incubator at 37℃for 30 minutes. After thawing, the product is kept in a refrigerator at 4 ℃ for refrigeration for standby.
The prepared hydrogel patch is characterized by a scanning electron microscope. As a result, as shown in FIG. 1, the hydrogel patch had a flat structure with a diameter of about 6mm (FIG. 1A) and a thickness of about 0.7mm (FIG. 1B), and a porous structure (FIG. 1C) inside, which was advantageous for drug loading.
Example 2: determination of photothermal efficiency
Fig. 2 is a measurement of the photo-thermal efficiency of a silver-containing graphene oxide hydrogel.
(a) The silver-containing graphene oxide patch prepared in example 1 was used at 808nm with a power of 2W/cm 2 Is irradiated by near infrared laser;
(b) Recording the temperature change in the irradiation process by using an infrared imager every 30 seconds;
(c) This experiment was repeated three times.
As a result, as shown in FIG. 2, after 1 minute of irradiation, the average temperature of the hydrogel was maintained at 42-45℃which indicates that the hydrogel patch prepared according to the present invention has good photothermal conversion ability and can maintain the temperature within the desired range for photothermal treatment for a certain period of time.
Example 3: determination of release efficiency of silver-containing graphene oxide hydrogel carrying 5-fluorouracil
1. Preparation of 5-fluorouracil-loaded silver-containing graphene oxide hydrogel
A. Preparation of silver-containing graphene oxide:
(a) Under ice water bath conditions, 1.5g of graphite powder, 2.5g of potassium persulfate and 2.5g of phosphorus pentoxide are sequentially added into 24mL of concentrated sulfuric acid, and stirred at 80 ℃ for 4.5 hours;
(b) Washing the solution prepared in A-a with ultrapure water until the pH is 7;
(c) Slowly adding the solution prepared in the step A-b and 7.5g of potassium permanganate into 60mL of concentrated sulfuric acid under certain conditions, heating to 35 ℃ and stirring for 6 hours;
(d) The solution prepared in A-c is diluted with 250mL of ultrapure water and then stirred for 2 hours, and then diluted with 300mL of ultrapure water;
(e) 10mL of 30% (w/v) hydrogen peroxide was added to the solution prepared in A-d, and after 12 hours of standing, the supernatant was decanted;
(f) Washing the precipitate obtained in A-e twice with 500mL of 1:10 hydrochloric acid prepared, and then washing with a large amount of ultrapure water until the pH reaches 7;
(g) Weighing 0.0088g of silver nitrate, dissolving in 10mL of ultrapure water, dropwise adding 1mg/mL of the solution obtained in the steps A-f and stirring for 30 minutes;
(h) Heating the solution prepared in the step A-g to 80 ℃, dropwise adding 8mol/L sodium hydroxide 2.2mL for reaction for 2 hours, and cooling to room temperature;
(i) Washing the solution prepared in the step A-h by ultrapure water until the pH value is 7, and obtaining the silver-containing graphene oxide.
B. Preparation of aqueous carrier gel
(a) Firstly, preparing 14% (w/v) polyvinyl alcohol solution and stirring for 4 hours at 90 ℃ to obtain a homogeneous state;
(b) Taking 0.8mL of the silver-containing graphene oxide prepared in the step A, mixing with 6mL of 14% (w/v) polyvinyl alcohol prepared in the step B-a, and stirring for 15 minutes to obtain a homogeneous solution;
(c) Adding 25mg/mL of 5-fluorouracil 4mL to the silver-containing graphene oxide solution obtained in the step B-B, and stirring for 15 minutes to obtain a homogeneous solution;
(d) Taking 0.1mL of the solution prepared in the step B-c into a 96-well plate;
(e) Freezing the flat plate obtained in the step B-d in a refrigerator at the temperature of minus 20 ℃ for 12 hours, and then thawing the flat plate in a constant temperature cabinet at the temperature of 37 ℃ for 30 minutes;
(f) putting the flat plate obtained in the step B-e into a refrigerator with the temperature of minus 20 ℃ for freezing for 12 hours, and then putting the flat plate into a constant temperature box with the temperature of 37 ℃ for thawing for 30 minutes;
(g) The plates obtained in B-f were frozen in a refrigerator at-20℃for 12 hours, and then thawed in a incubator at 37℃for 30 minutes. After thawing, the product is kept in a refrigerator at 4 ℃ for refrigeration for standby.
2. Determination of the efficiency of 5-fluorouracil Release in hydrogels
(a) Experiments were performed in 8 groups, each group taking 1 hydrogel patch prepared in example 1 and placing in 1mL of PBS solution;
(b) The hydrogels were divided into an initial time group, a 2-hour group, a 4-hour group, a 6-hour group, an 8-hour group, a 24-hour group, a 48-hour group, and a 72-hour group in order;
(c) Taking 0.5mL of supernatant fluid in the sample at the time node and collecting an absorption spectrum on an ultraviolet-visible spectrophotometer;
(d) Each set of experiments was repeated three times.
As a result, as shown in fig. 3, the drug in the hydrogel patch was gradually released within 72 hours. This means that the drug-loaded hydrogel synthesized by the invention can maintain the state of drug release for a period of time after being implanted into eyes, thereby better playing the role of drug treatment.
Example 4: evaluation of drug-loaded silver-containing graphene oxide hydrogel applied to glaucoma filtration
1. Preparation of 5-fluorouracil-loaded silver-containing graphene oxide hydrogel
A. Preparation of silver-containing graphene oxide:
(a) Under ice water bath conditions, 1.5g of graphite powder, 2.5g of potassium persulfate and 2.5g of phosphorus pentoxide are sequentially added into 24mL of concentrated sulfuric acid, and stirred at 80 ℃ for 4.5 hours;
(b) Washing the solution prepared in A-a with ultrapure water until the pH is 7;
(c) Slowly adding the solution prepared in the step A-b and 7.5g of potassium permanganate into 60mL of concentrated sulfuric acid under certain conditions, heating to 35 ℃ and stirring for 6 hours;
(d) The solution prepared in A-c is diluted with 250mL of ultrapure water and then stirred for 2 hours, and then diluted with 300mL of ultrapure water;
(e) 10mL of 30% (w/v) hydrogen peroxide was added to the solution prepared in A-d, and after 12 hours of standing, the supernatant was decanted;
(f) Washing the precipitate obtained in A-e twice with 500mL of 1:10 hydrochloric acid prepared, and then washing with a large amount of ultrapure water until the pH reaches 7;
(g) Weighing 0.0088g of silver nitrate, dissolving in 10mL of ultrapure water, dropwise adding 1mg/mL of the solution obtained in the steps A-f and stirring for 30 minutes;
(h) Heating the solution prepared in the step A-g to 80 ℃, dropwise adding 8mol/L sodium hydroxide 2.2mL for reaction for 2 hours, and cooling to room temperature;
(i) Washing the solution prepared in the step A-h by ultrapure water until the pH value is 7, and obtaining the silver-containing graphene oxide.
B. Preparation of aqueous carrier gel
(a) Firstly, preparing 14% (w/v) polyvinyl alcohol solution and stirring for 4 hours at 90 ℃ to obtain a homogeneous state;
(b) Taking 0.8mL of the silver-containing graphene oxide prepared in the step A, mixing with 6mL of 14% (w/v) polyvinyl alcohol prepared in the step B-a, and stirring for 15 minutes to obtain a homogeneous solution;
(c) Adding 25mg/mL of 5-fluorouracil 4mL to the silver-containing graphene oxide solution obtained in the step B-B, and stirring for 15 minutes to obtain a homogeneous solution;
(d) Taking 0.1mL of the solution prepared in the step B-c into a 96-well plate;
(e) Freezing the flat plate obtained in the step B-d in a refrigerator at the temperature of minus 20 ℃ for 12 hours, and then thawing the flat plate in a constant temperature cabinet at the temperature of 37 ℃ for 30 minutes;
(f) putting the flat plate obtained in the step B-e into a refrigerator with the temperature of minus 20 ℃ for freezing for 12 hours, and then putting the flat plate into a constant temperature box with the temperature of 37 ℃ for thawing for 30 minutes;
(g) The plates obtained in B-f were frozen in a refrigerator at-20℃for 12 hours, and then thawed in a incubator at 37℃for 30 minutes. After thawing, the product is kept in a refrigerator at 4 ℃ for refrigeration for standby.
2. Evaluation of the application of the aqueous Carrier gel to glaucoma filtration
A. Establishment of rabbit eye filterability operation model
(a) Marking an eye surgical site;
(b) Weighing, and performing intravenous injection on the auricle of chloral hydrate with the concentration of 5mL and 10%;
(c) Cutting eyelashes, sterilizing with iodophor for 3 times, and spreading sterile towel;
(d) The obucaine hydrochloride eye drops are dropped on the operation eye, and an eyelid opener opens the eyelid;
(e) Cornea traction is carried out by using 6-0 ophthalmic micro-suture;
(f) The conjunctiva was cut along the limbus 1mm or so, an L-shaped conjunctival flap was made and then blunt-separated posteriorly, exposing the sclera approximately 10mm x 10mm in size;
(g) Inserting a 22G indwelling needle into the anterior chamber 1-2mm after the limbus, inserting 2-3mm beyond the limbus, subtracting the redundant catheter and fixing;
(h) The drainage tube was secured to the scleral surface using a 10-0 suture.
B. Grouping experiments
(a) The rabbits with successful molding were divided into three groups for subsequent experiments: (1) a physiological saline group; (2) a group of 5-fluorouracils; (3) a set of aqueous gels;
(b) Physiological saline group: 1mL of physiological saline is used for flushing the conjunctival flap and the scleral clearance, and then the conjunctival flap is continuously sutured and closed;
(c) 5-fluorouracil group: 1mL 25mg/mL 5-fluorouracil is taken to flush the conjunctival flap and the scleral space, and then the conjunctival flap is continuously sutured closed;
(d) Water-carrying gel group: taking the liquid-carrying hydrogel patch prepared in the example 4, placing the liquid-carrying hydrogel patch in a gap between a conjunctival flap and a sclera, and then continuously suturing and closing the conjunctival flap;
(e) The antibiotic eye ointment is smeared on eyes and marked;
(f) Using 808nm NIR laser (2W/cm) at 3, 6, 9, 12, 15, 18, 21, 24, 27 days post-operatively 2 ) The ocular hydrogel region of the drug-loaded hydrogel group animals was irradiated for 5 minutes.
C. Observation and evaluation of postoperative index
(a) Postoperative intraocular pressure monitoring: the obucaine hydrochloride eye drops on the eye surface, and the rebound tonometer is used for detecting the intraocular pressure of the experimental rabbit for 3 days/time;
(b) Anterior ocular segment examination: the obucaine hydrochloride eye drops on the eye surface, and the eye surface, cornea, anterior chamber depth and bleb condition are observed by using a handheld slit lamp and photographed.
The results are shown in FIG. 4, the intraocular pressure of the rabbit eyes of the hydrogel group is lower (FIG. 4-A), the scar degree after operation is lighter, and the survival rate of the blebs is obviously improved (FIG. 4-B).
The experiment proves that the eye photothermal treatment carrier disclosed by the invention not only can prolong the retention time of the medicine in eyes to better play a role of medicine treatment, but also has good photothermal conversion capability, can maintain the temperature in a photothermal treatment range, and can effectively weaken the scar degree after glaucoma filtration operation under near infrared light irradiation.
The foregoing description of the preferred embodiments of the present invention has been presented only in terms of those specific and detailed descriptions, and is not, therefore, to be construed as limiting the scope of the invention. It should be noted that modifications, improvements and substitutions can be made by those skilled in the art without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (6)
1. The preparation method of the eye photothermal therapy carrier is characterized by comprising the following steps of:
A. preparation of silver-containing graphene oxide:
a) Sequentially adding graphite powder, potassium persulfate and phosphorus pentoxide into concentrated sulfuric acid, stirring at 50-100 ℃ for 1-5 hours, and then washing with ultrapure water until the pH of the solution is 6-8;
b) Slowly adding the solution obtained in the step A-a) and potassium permanganate into concentrated sulfuric acid, heating to 20-40 ℃ and stirring for 4-8 hours, and then diluting with ultrapure water and stirring;
c) Adding 10% -40% (w/v) hydrogen peroxide into the solution obtained in the step A-b), standing for 8-14 hours, removing supernatant to obtain precipitate, and washing with hydrochloric acid and ultrapure water until the pH of the solution is 6-8;
d) Dropwise adding the solution obtained in the step A-c) into a silver nitrate solution, stirring for 20-60 minutes, heating the solution to 50-100 ℃, dropwise adding 1-10mol/L sodium hydroxide to react for 1-5 hours, cooling the reaction solution to room temperature, and washing with ultrapure water until the pH value is 6-8 to obtain silver-containing graphene oxide;
B. preparation of hydrogels:
a) Preparing 10% -15% (w/v) polyvinyl alcohol solution, and stirring at 70-100 ℃ for 1-5 hours to make the solution in a homogeneous state;
b) Mixing the silver-containing graphene oxide prepared in the step A with the polyvinyl alcohol solution prepared in the step B-a), and stirring for 10-30 minutes to obtain a homogeneous solution;
c) Adding 5-fluorouracil with the concentration of 20-30mg/mL into the homogeneous solution obtained in the step B-B), stirring for 5-30 minutes, freezing the solution at-20 ℃ and thawing at 37 ℃ for three times, and refrigerating the obtained product at 4 ℃.
2. The preparation method of the eye photothermal therapy carrier according to claim 1, wherein the raw materials in the step A are mixed according to parts by weight: 0.5-2.0 parts of graphite powder, 0.5-3.0 parts of potassium persulfate, 0.5-3.0 parts of phosphorus pentoxide and 1.0-8.0 parts of potassium permanganate.
3. The method for preparing the eye photothermal therapy carrier according to claim 1, wherein the solution ratios in the steps A-d) are as follows in parts by volume: 5-15 parts of the solution obtained in the step A-c), 5-15 parts of silver nitrate solution and 2-3 parts of sodium hydroxide.
4. The method for preparing a photothermal ocular therapy carrier according to claim 3, wherein the preparation method of the silver nitrate solution is to dissolve 0.001-0.01-g silver nitrate in 5-15mL ultrapure water; the concentration of the solution obtained in the step A-c) is regulated to be 0.5-1.5mg/mL before the solution is dripped into the silver nitrate solution.
5. The method for preparing the eye photothermal therapy carrier according to claim 1, wherein the solution in the step B is prepared from the following components in parts by volume: 0.1-1 part of silver-containing graphene oxide, 5-10 parts of polyvinyl alcohol solution and 1-5 parts of 5-fluorouracil.
6. The method for preparing a photothermal ophthalmic therapeutic carrier according to claim 1, wherein the freezing time in step B-c) is 5-15 hours and the thawing time is 15-45 minutes.
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