CN113941298A - Preparation method of novel eye photothermal treatment carrier - Google Patents
Preparation method of novel eye photothermal treatment carrier Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 16
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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
- 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
- B01J13/0056—Preparation of gels containing inorganic material and water
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- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
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- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
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- A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
- A61N2005/0643—Applicators, probes irradiating specific body areas in close proximity
- A61N2005/0645—Applicators worn by the patient
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- A61N2005/0648—Applicators worn by the patient the applicator adapted to be worn on the head the light being directed to the eyes
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- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
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Abstract
The invention discloses a preparation method of a novel eye photothermal treatment carrier. The method takes hydrogel as a carrier, and the silver-containing graphene oxide with photoresponse 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 for a certain time in eyes to better play a role; on the other hand, the hydrogel can rapidly respond to near infrared light, can maintain the temperature in the range required by photothermal therapy, and can effectively induce the apoptosis of conjunctival fibroblasts under the irradiation of the near infrared light, thereby achieving the purpose of maintaining the filtering bleb after glaucoma operation for a long time.
Description
Technical Field
The invention belongs to the technical field of biological materials, and particularly relates to a preparation method of a novel eye photothermal treatment carrier.
Background
Glaucoma is the irreversible blinding eye disease ranked at the top at present, and the main clinical feature of the glaucoma is pathological intraocular pressure increase, and intraocular pressure reduction is the only treatment means which is verified by multi-center clinical tests and has exact curative effect. When the effect of medicine and laser treatment is not good, filtration surgery treatment is considered. At present, the compound trabeculectomy is still the mainstream of various filtering operations, but the success rate of the operations is not satisfactory, and the main reason is that the incision is over-healed after the operations. Therefore, the anti-scarring drug is required to be applied during or after the operation to regulate the healing process of the wound and prevent the excessive proliferation of the fibroblast in the filtration zone; the use of anti-scarring drugs also leads to an increased incidence of postoperative adverse reactions. To date, there is no way or drug to perfectly balance the relationship between aqueous humor filtration, post-operative wound healing, and reduce the incidence of post-operative complications. And in recent years, the development of rapid nano material technology provides a new way and hope for solving the problem.
Graphene is a nano material with a single-layer two-dimensional honeycomb lattice structure in which carbon atoms are hybridized and connected. Graphene oxide is the most important derivative thereof, not only has a two-dimensional planar structure similar to graphene, but also is endowed with excellent hydrophilicity and surface modification possibility by a large number of oxygen-containing functional groups distributed thereon. In recent years, the application research of graphene in the medical field is to realize the synergistic chemotherapy-photothermal therapy of tumors by utilizing the excellent photothermal conversion performance and the strong drug loading capacity of the graphene. The photothermal therapy realized by the near-infrared laser can realize controllable treatment at a specific time and a specific part, and has high flexibility and safety.
Based on the above situation, there is an urgent need for a more controllable, intelligent and safe method for regulating the healing process of the wound after glaucoma surgery.
Disclosure of Invention
Aiming at the problems in the background technology, the invention takes New Zealand white rabbits as the early test object, develops a novel eye photothermal treatment carrier, and explores the situation of applying the synergistic chemotherapy-photothermal therapy to the scar after glaucoma filtration.
The first purpose of the invention is to establish a novel eye photothermal therapy carrier.
The second purpose of the invention is to provide a controllable, intelligent and safe method for regulating and controlling the scar degree of the wound after glaucoma filtration so as to improve the success rate of the operation.
In order to realize the purpose, the invention is realized by the following technical scheme:
a preparation method of a novel ocular photothermal therapy carrier comprises the following steps:
A. preparing 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 value 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 ℃, stirring for 4-8 hours, and then diluting and stirring with ultrapure water;
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 a 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 hydrogel:
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 ℃, unfreezing the solution at 37 ℃ for three times, and refrigerating the obtained product at 4 ℃.
Further, the raw materials in the step A are in the following proportion 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 ratio in the step A-d) is 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) needs to be adjusted 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).
And 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 of the step B-c) is 5-15 hours, and the unfreezing 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 hydrogel patch has a certain photothermal conversion effect to achieve the purpose of photothermal therapy.
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 aim of eye treatment.
Further, the novel ocular photothermal therapy vehicle is applied to the treatment of glaucoma-associated ocular diseases.
The novel eye photothermal treatment carrier prepared by the invention has good biocompatibility, and can allow the medicine to stay in eyes for a certain time to play a role; meanwhile, the near-infrared light can be responded rapidly, the temperature can be maintained in the range required by photo-thermal treatment, and the conjunctival fibroblast can be induced to die effectively under the irradiation of the near-infrared light. After the hydrogel is implanted, the survival rate of the filtering bleb after rabbit eye surgery is obviously improved.
Compared with the prior art, the invention has the beneficial effects that:
1. the novel eye photothermal treatment carrier synthesized by the invention can prolong the retention time of the medicine in the eyes.
2. The novel ocular photothermal therapy vector synthesized by the invention has good photothermal conversion capability and can maintain the temperature in the required range of photothermal therapy.
3. The novel eye photothermal therapy vector synthesized by the invention can effectively weaken scar after glaucoma filtration under near infrared light irradiation.
Drawings
Figure 1 is a topographical characterization of a silver-containing graphene oxide hydrogel.
Fig. 2 is a measurement of photothermal efficiency of a silver-containing graphene oxide hydrogel.
Fig. 3 is a determination of the release efficiency of drug-loaded silver-containing graphene oxide hydrogel.
Fig. 4 is an evaluation of the anti-scarring effect of the drug-loaded silver-containing graphene oxide hydrogel after application to 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 below with reference to the embodiments. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1: morphology characterization of silver-containing graphene oxide hydrogel
A. Preparing silver-containing graphene oxide:
(a) under the condition of ice-water bath, 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 for 4.5 hours at 80 ℃;
(b) washing the solution prepared by A-a with ultrapure water until the pH is 7;
(c) slowly adding the solution prepared by A-b and 7.5g of potassium permanganate into 60mL of concentrated sulfuric acid under a certain condition, heating to 35 ℃, and stirring for 6 hours;
(d) diluting the solution prepared by the A-c with 250mL of ultrapure water, continuing stirring for 2 hours, and then diluting with 300mL of ultrapure water;
(e) adding 10mL of 30% (w/v) hydrogen peroxide into the solution prepared from A-d, standing for 12 hours, and pouring off the supernatant;
(f) washing the precipitate obtained from A-e twice with 500mL1:10 hydrochloric acid, and then washing with large amount of ultrapure water until the pH reaches 7;
(g) weighing 0.0088g of silver nitrate, dissolving the silver nitrate in 10mL of ultrapure water, dropwise adding 10mL of the solution obtained in the step A-f at a concentration of 1mg/mL, and stirring for 30 minutes;
(h) heating the solution prepared by A-g to 80 ℃, dropwise adding 2.2mL of 8mol/L sodium hydroxide, reacting for 2 hours, and then cooling to room temperature;
(i) and washing the solution prepared in the step A-h by using ultrapure water until the pH value is 7, thus obtaining the silver-containing graphene oxide.
B. Preparation of hydrogels
(a) Firstly, preparing a 14% (w/v) polyvinyl alcohol solution and stirring the solution 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 by the B-B to a 96-well plate;
(d) putting the flat plate obtained from the step B-c into a refrigerator with the temperature of-20 ℃ for freezing for 12 hours, and then putting the flat plate into a thermostat with the temperature of 37 ℃ for unfreezing for 30 minutes;
(e) putting the flat plate obtained from the step B-d into a refrigerator with the temperature of-20 ℃ for freezing for 12 hours, and then putting the flat plate into a thermostat with the temperature of 37 ℃ for unfreezing for 30 minutes;
(f) and (4) freezing the flat plate obtained from the step B-e in a refrigerator at the temperature of-20 ℃ for 12 hours, and then unfreezing the flat plate in a thermostat at the temperature of 37 ℃ for 30 minutes. After thawing, the product was kept in a refrigerator at 4 ℃ for further use.
And (3) characterizing the prepared hydrogel patch by a scanning electron microscope. As a result, as shown in FIG. 1, the hydrogel patch has a flat structure with a diameter of about 6mm (FIG. 1A) and a thickness of about 0.7mm (FIG. 1B), and has a porous structure inside (FIG. 1C) to facilitate loading of the drug.
Example 2: measurement of photothermal efficiency
Fig. 2 is a measurement of photothermal efficiency of a silver-containing graphene oxide hydrogel.
(a) The silver-containing graphene oxide patch prepared in example 1 was used at 808nm and a power of 2W/cm2Irradiating with near-infrared laser;
(b) recording the temperature change in the irradiation process by using an infrared imager every 30 seconds;
(c) the experiment was repeated three times.
As a result, as shown in FIG. 2, the average temperature of the hydrogel was maintained at 42 to 45 ℃ after 1 minute of irradiation, indicating 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 therapy for a certain period of time.
Example 3: determination of release efficiency of 5-fluorouracil-loaded silver-containing graphene oxide hydrogel
1. Preparation of 5-fluorouracil-loaded silver-containing graphene oxide hydrogel
A. Preparing silver-containing graphene oxide:
(a) under the condition of ice-water bath, 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 for 4.5 hours at 80 ℃;
(b) washing the solution prepared by A-a with ultrapure water until the pH is 7;
(c) slowly adding the solution prepared by A-b and 7.5g of potassium permanganate into 60mL of concentrated sulfuric acid under a certain condition, heating to 35 ℃, and stirring for 6 hours;
(d) diluting the solution prepared by the A-c with 250mL of ultrapure water, continuing stirring for 2 hours, and then diluting with 300mL of ultrapure water;
(e) adding 10mL of 30% (w/v) hydrogen peroxide into the solution prepared from A-d, standing for 12 hours, and pouring off the supernatant;
(f) washing the precipitate obtained from A-e twice with 500mL1:10 hydrochloric acid, and then washing with large amount of ultrapure water until the pH reaches 7;
(g) weighing 0.0088g of silver nitrate, dissolving the silver nitrate in 10mL of ultrapure water, dropwise adding 10mL of the solution obtained in the step A-f at a concentration of 1mg/mL, and stirring for 30 minutes;
(h) heating the solution prepared by A-g to 80 ℃, dropwise adding 2.2mL of 8mol/L sodium hydroxide, reacting for 2 hours, and then cooling to room temperature;
(i) and washing the solution prepared in the step A-h by using ultrapure water until the pH value is 7, thus obtaining the silver-containing graphene oxide.
B. Preparation of drug-loaded hydrogel
(a) Firstly, preparing a 14% (w/v) polyvinyl alcohol solution and stirring the solution 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 4mL of 25mg/mL 5-fluorouracil into the silver-containing graphene oxide solution obtained in B-B, and stirring for 15 minutes to obtain a homogeneous solution;
(d) taking 0.1mL of the solution prepared by the B-c to a 96-well plate;
(e) putting the flat plate obtained from the step B-d into a refrigerator with the temperature of-20 ℃ for freezing for 12 hours, and then putting the flat plate into a thermostat with the temperature of 37 ℃ for unfreezing for 30 minutes;
(f, putting the flat plate obtained from the step B-e into a refrigerator at the temperature of-20 ℃ for freezing for 12 hours, and then putting the flat plate into a thermostat at the temperature of 37 ℃ for unfreezing for 30 minutes;
(g) and (4) putting the flat plate obtained from the step (B-f) into a refrigerator with the temperature of-20 ℃ for freezing for 12 hours, and then putting the flat plate into a thermostat with the temperature of 37 ℃ for unfreezing for 30 minutes. After thawing, the product was kept in a refrigerator at 4 ℃ for further use.
2. Determination of 5-Fluorouracil Release efficiency in hydrogels
(a) The experiment was performed in 8 groups, each group taking 1 hydrogel patch prepared in example 1 into 1ml pbs solution;
(b) sequentially dividing the hydrogel 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;
(c) taking 0.5mL of supernatant 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.
The result is shown in fig. 3, where the drug in the hydrogel patch is gradually released within 72 hours. This means that the synthesized drug-loaded hydrogel can keep the drug release state for a period of time after being implanted into eyes, thereby better playing the role of drug therapy.
Example 4: evaluation of application of drug-loaded silver-containing graphene oxide hydrogel in glaucoma filtration
1. Preparation of 5-fluorouracil-loaded silver-containing graphene oxide hydrogel
A. Preparing silver-containing graphene oxide:
(a) under the condition of ice-water bath, 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 for 4.5 hours at 80 ℃;
(b) washing the solution prepared by A-a with ultrapure water until the pH is 7;
(c) slowly adding the solution prepared by A-b and 7.5g of potassium permanganate into 60mL of concentrated sulfuric acid under a certain condition, heating to 35 ℃, and stirring for 6 hours;
(d) diluting the solution prepared by the A-c with 250mL of ultrapure water, continuing stirring for 2 hours, and then diluting with 300mL of ultrapure water;
(e) adding 10mL of 30% (w/v) hydrogen peroxide into the solution prepared from A-d, standing for 12 hours, and pouring off the supernatant;
(f) washing the precipitate obtained from A-e twice with 500mL1:10 hydrochloric acid, and then washing with large amount of ultrapure water until the pH reaches 7;
(g) weighing 0.0088g of silver nitrate, dissolving the silver nitrate in 10mL of ultrapure water, dropwise adding 10mL of the solution obtained in the step A-f at a concentration of 1mg/mL, and stirring for 30 minutes;
(h) heating the solution prepared by A-g to 80 ℃, dropwise adding 2.2mL of 8mol/L sodium hydroxide, reacting for 2 hours, and then cooling to room temperature;
(i) and washing the solution prepared in the step A-h by using ultrapure water until the pH value is 7, thus obtaining the silver-containing graphene oxide.
B. Preparation of drug-loaded hydrogel
(a) Firstly, preparing a 14% (w/v) polyvinyl alcohol solution and stirring the solution 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 4mL of 25mg/mL 5-fluorouracil into the silver-containing graphene oxide solution obtained in B-B, and stirring for 15 minutes to obtain a homogeneous solution;
(d) taking 0.1mL of the solution prepared by the B-c to a 96-well plate;
(e) putting the flat plate obtained from the step B-d into a refrigerator with the temperature of-20 ℃ for freezing for 12 hours, and then putting the flat plate into a thermostat with the temperature of 37 ℃ for unfreezing for 30 minutes;
(f, putting the flat plate obtained from the step B-e into a refrigerator at the temperature of-20 ℃ for freezing for 12 hours, and then putting the flat plate into a thermostat at the temperature of 37 ℃ for unfreezing for 30 minutes;
(g) and (4) putting the flat plate obtained from the step (B-f) into a refrigerator with the temperature of-20 ℃ for freezing for 12 hours, and then putting the flat plate into a thermostat with the temperature of 37 ℃ for unfreezing for 30 minutes. After thawing, the product was kept in a refrigerator at 4 ℃ for further use.
2. Evaluation of drug-loaded hydrogel applied to glaucoma filtration
A. Establishment of rabbit eye filtering operation model
(a) Marking the eye surgery site;
(b) weighing, general anesthesia by ear-edge intravenous injection using 5mL 10% chloral hydrate;
(c) shearing off eyelashes and iodophor, sterilizing for 3 times, and spreading sterile towel;
(d) the oxybuprocaine hydrochloride eye drops are dropped on the operation eye, and the eyelid is opened by the eyelid opener;
(e) using a 6-0 ophthalmic micro suture for corneal traction;
(f) cutting conjunctiva about 1mm behind limbus, making L-shaped conjunctival flap, separating backward, and exposing sclera of about 10mm × 10 mm;
(g) inserting a 22G indwelling needle into the anterior chamber at 1-2mm behind the limbus, inserting the indwelling needle into the anterior chamber 2-3mm beyond the limbus, subtracting the redundant catheter and fixing;
(h) the drainage tube was secured to the scleral surface using 10-0 sutures.
B. Grouping experiment
(a) The rabbits that were successfully molded were divided into three groups for subsequent experiments: a physiological saline solution group; ② 5-fluorouracil group; ③ a drug-loaded hydrogel group;
(b) physiological saline group: 1mL of physiological saline is taken to wash the gap between the conjunctival flap and the sclera, and then the conjunctival flap is continuously sutured and closed;
(c) 5-fluorouracil group: 1mL of 25mg/mL of 5-fluorouracil is taken to wash the conjunctival flap and the sclera gap, and then the conjunctival flap is closed by continuous suturing;
(d) drug-loaded hydrogel group: taking the drug-loaded hydrogel patch prepared in the example 4, placing the patch in a gap between the conjunctival flap and the sclera, and then continuously suturing to close the conjunctival flap;
(e) the antibiotic eye ointment is smeared on eyes and marked;
(f) using 808nm NIR laser (2W/cm) 3, 6, 9, 12, 15, 18, 21, 24, 27 days after operation2) The ocular hydrogel regions of the drug-loaded hydrogel group animals were irradiated for 5 minutes.
C. Observation and evaluation of postoperative index
(a) Monitoring postoperative intraocular pressure: dripping oxybuprocaine hydrochloride eye drops on the ocular surface, and detecting the intraocular pressure of the experimental rabbit by using a rebound tonometer for 3 days/time;
(b) examination of anterior segment: oxybuprocaine hydrochloride eye drops were dropped on the ocular surface, and the ocular surface, cornea, anterior chamber depth and condition of the filter bulb were observed using a hand-held 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 degree of postoperative scarring is lower, and the survival rate of the filter blebs is obviously improved (fig. 4-B).
The experiment proves that the novel eye photothermal treatment carrier disclosed by the invention can prolong the retention time of the drug in the eye to better exert the drug treatment effect, has good photothermal conversion capability, can maintain the temperature in the photothermal treatment range, and effectively weakens the scarring degree after glaucoma filtration under near-infrared light irradiation.
The foregoing merely represents preferred embodiments of the invention, which are described in some detail and detail, and therefore should not be construed as limiting the scope of the invention. It should be noted that, for those skilled in the art, various changes, modifications and substitutions can be made without departing from the spirit of the present invention, and these are all within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (8)
1. The preparation method of the novel eye photothermal treatment carrier is characterized by comprising the following steps:
A. preparing 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 value 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 ℃, stirring for 4-8 hours, and then diluting and stirring with ultrapure water;
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 a 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 hydrogel:
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 ℃, unfreezing the solution at 37 ℃ for three times, and refrigerating the obtained product at 4 ℃.
2. The preparation method of the novel ocular photothermal therapy carrier according to claim 1, wherein the raw materials in the step A are in the following ratio 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 novel ophthalmic photothermal treatment carrier according to claim 1, wherein the ratio of the solutions in the steps A-d) is as follows according to the 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 novel vehicle for photothermal treatment of an eye according to claim 3, wherein said silver nitrate solution is prepared by 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) needs to be adjusted to be 0.5-1.5mg/mL before the solution is dripped into the silver nitrate solution.
5. The method for preparing a novel ophthalmic photothermal treatment carrier according to claim 1, wherein the ratio of the solutions in the step B is as follows according to the 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 novel vehicle for ocular photothermal therapy according to claim 1, wherein the freezing time in step B-c) is 5-15 hours, and the thawing time is 15-45 minutes.
7. The novel ocular photothermal therapy carrier prepared by the preparation method according to any one of claims 1 to 6 is used for treating ocular diseases.
8. The novel ophthalmic photothermal treatment vehicle use according to claim 7, wherein the ophthalmic disease is a glaucoma-related disease.
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