CN117771163A - Medicine for treating eye diseases, continuous administration device and preparation method thereof - Google Patents
Medicine for treating eye diseases, continuous administration device and preparation method thereof Download PDFInfo
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- CN117771163A CN117771163A CN202311372463.6A CN202311372463A CN117771163A CN 117771163 A CN117771163 A CN 117771163A CN 202311372463 A CN202311372463 A CN 202311372463A CN 117771163 A CN117771163 A CN 117771163A
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Abstract
The utility model discloses a medicine for treating eye diseases, a continuous administration device and a preparation method thereof, and belongs to the technical field of eye disease treatment. The medicine for treating eye diseases is triamcinolone acetonide hydrogel prepared from succinic anhydride, triamcinolone acetonide and pyridine; the continuous administration device is prepared by carrying out physical transformation on the structure of the existing continuous administration device through a 3D printing technology and based on TPU materials. The continuous administration device can be directly placed outside the eye and under the inferior rectus muscle, an administration pump is not required to be connected, tubeless connection and portability are realized through medicine slow release, and the concentration of the medicine in the eye during transscleral administration can be improved, so that the medicine effect is more durable; the drug for treating the eye diseases adopts a self-assembled nano structure, can increase the solubility of triamcinolone acetonide, is released from gel through passive diffusion and degradation, and is more stable and uniform in release.
Description
Technical Field
The utility model relates to the technical field of eye disease treatment, in particular to a medicament for treating eye disease, a continuous administration device and a preparation method thereof.
Background
How to effectively transfer the medicine to the tissues of the back part of the eye to treat the diseases of the back part of the eye (including age-related macular degeneration, retinal vascular diseases, chronic uveitis, infectious endophthalmitis, and the like) is a research hot spot in the field of treatment of ophthalmic diseases. Because of the existence of various 'membranous barriers' in eyes due to the special anatomical physiological structures, such as corneal epithelium barrier, blood-aqueous humor barrier and blood-retina barrier, the drugs are difficult to reach effective treatment concentration in intraocular tissues through the 'membranous barriers' by ocular surface drug dropping and intravenous administration route, and intraocular drug injection has the risks of retinal toxicity and intraocular infection, researchers hope to seek a new administration route to solve the existing defects. The transscleral administration route has become a research hot spot for exploring the drug delivery of the posterior segment tissue of the eye in recent years because of the high and safe permeability of the scleral drug, and how to deliver therapeutic concentration of the drug to the posterior segment cake tissue of the eye by the transscleral route has become a difficulty and an important point.
The sclera occupies 5/6 of the whole eye surface area, and most of the sclera components are composed of collagen fibers which are uniformly arranged and loose in structure, so that the sclera has the advantages of large medicine absorption area and high medicine permeability for cornea, and hydrophilic medicine can penetrate through the sclera more easily. Many scholars at home and abroad have studied the permeability of the sclera to various drugs, including: betamethasone, oligonucleotides, albumin and anti-angiogenic factors. Studies have shown that the absorption of drug by the sclera is based on steady state flux of drug through the sclera, meaning that the drug must be in contact with the scleral surface for a sufficient period of time to reach steady state flux. Transscleral administration is also known as peribulbar administration and includes subconjunctival administration, tenon subcapsular administration, retrobulbar and peribulbar injection. Transscleral routes of administration have the advantage of large drug absorption areas, high drug permeability, and low trauma compared to other routes of administration. Compared with intraocular injection, transscleral administration avoids intraocular interference caused by breaking the eyeball, has no systemic side effect caused by intravenous administration, does not need frequent administration, is more efficient than ocular surface administration, and has higher compliance of patients.
The patent publication CN213758903U discloses a transscleral sustained drug delivery device, but how to transform the structure of the sustained drug delivery device into a physical object for clinical application is continuously studied. In addition, carbomer gel is adopted in the use description of the sustained-administration device, and after subconjunctival or peribulbar injection, the drug is deposited in tissues, and after carbomer gelation, triamcinolone acetonide is released unevenly, so that the drug is easy to be hard to be absorbed, drug residues are easy to be formed, and the bioavailability of the drug is influenced.
Disclosure of Invention
Aiming at the problems, the utility model aims to provide a drug for treating eye diseases, a sustained drug administration device and a preparation method thereof, which can improve the concentration of the drug in eyes during transscleral drug administration, so that the drug effect is more durable, and the drug for treating eye diseases adopts a self-assembled nano structure, can increase the solubility of triamcinolone acetonide, and is released from gel through passive diffusion and degradation, so that the release is more stable and uniform.
In order to achieve the above purpose, the technical scheme adopted by the utility model is as follows:
a medicament for the treatment of an ocular disorder, characterized in that: the medicine is triamcinolone acetonide hydrogel; the triamcinolone acetonide hydrogel comprises the following components: succinic anhydride, triamcinolone acetonide, and pyridine.
Furthermore, the utility model also comprises a preparation method of the medicament for treating eye diseases, which is characterized by comprising the following steps,
s1: preparing triamcinolone acetonide gel with the mass concentration of 2-5%;
s2: co-dissolving triamcinolone acetonide gel, succinic anhydride and pyridine;
s3: removing the organic solvent in the mixed solution obtained in the step S2, adding water, centrifuging and collecting fine crystals;
s4: the fine crystals collected in step S3 were dissolved in PBS buffer solution and left at 37℃for 1-2 days to form triamcinolone acetonide hydrogel.
Further, the specific procedure of step S2 includes the steps of co-dissolving 400mg triamcinolone acetonide gel, 280mg succinic anhydride and 10mL pyridine and stirring at room temperature for 3-4h.
Further, the specific operation steps of step S4 include: the fine crystals collected in step S3 were dissolved in PBS buffer solution having ph=7.4 to give a final concentration of 400mg/mL, and left at 37 ℃ for 35 hours to form triamcinolone acetonide hydrogel.
Further, the present utility model also includes a sustained-administration device for an ophthalmic disease treatment drug, characterized in that: the sustained drug delivery device includes a Tenon subcapsular implant; the Tenon subcapsular implant consists of an arc body cavity structure and wing-shaped fixing plates arranged on two sides of the arc body cavity structure; the circular arc body cavity structure is communicated with a medicine injection port for injecting medicines as described above, and the continuous medicine feeding device is prepared through 3D printing.
Furthermore, the utility model also comprises a preparation method of the sustained drug administration device for treating eye diseases, which is characterized by comprising the following steps,
step A:3D printing pretreatment, obtaining a digital model of the continuous drug administration device;
and (B) step (B): manufacturing a 3D model of the continuous drug administration device;
step C: post-processing of the 3D model of the continuous drug administration device;
step D: and (3) laminating by using a TPU material to obtain the continuous drug delivery device for 3D printing.
Further, the specific operation of the step B comprises the following steps of cutting the digital model of the continuous drug delivery device in the step A into a series of continuous transverse layers, converting the digital model into a standard surface subdivision language file readable by a 3D printer, transmitting data to the printer, using a resin material to scan and print in the printer by laser, spraying the material layer by layer on a three-dimensional space of the series of continuous transverse layers according to a layer thickness of 0.1mm, and finally preparing the three-dimensional object.
Further, the specific operation of the step C comprises the steps of taking out the model deposited on the printing platform in the step B, washing uncured resin covered on the model by using an ultrasonic cleaner, removing the supporting structure by using a cutter, and performing model surface painting process to finish model curing.
Further, the specific operation of the step D comprises the following steps of injecting silica gel into a silica gel cavity to manufacture a silica gel mold, placing the mold obtained after the post-treatment of the step C into the silica gel mold, then placing the mold into a vacuum machine, injecting TPU material with the hardness of 50A-60A, and opening the mold after the silica gel mold is cooled to obtain the soft continuous eye administration device.
The beneficial effects of the utility model are as follows:
1. the medicine for treating eye diseases is the triamcinolone acetonide hydrogel prepared from succinic anhydride, triamcinolone acetonide and pyridine, and the triamcinolone acetonide hydrogel adopts a self-assembled nano structure, so that the solubility of triamcinolone acetonide can be increased, and the triamcinolone acetonide hydrogel is released from gel through passive diffusion and degradation, is more uniform in release, and has a more stable medicine release function compared with Yu Kabo mu gel material.
2. The continuous drug delivery device for the eye disease treatment drug disclosed by the utility model is used for carrying out physical transformation on the structure of the conventional continuous drug delivery device through a 3D printing technology, and is prepared based on TPU materials, the finally obtained finished product can be directly placed outside the eye and under the inferior rectus muscle without connecting a drug delivery pump, the tubeless connection and the portable para-suture bulbar conjunctiva are realized through drug slow release, and the concentration of the eye drug during transscleral drug delivery can be improved, so that the drug effect is more durable.
3. The continuous administration device for 3D printing preparation adopts TPU material, and the liquid resin material used in the SLA light curing molding technology has slight toxicity and is easy to cause skin allergy after human body contact, so the material is not suitable for eyeball implantation administration after printing. After the model is printed out through 3D, the model copying is carried out on the drug delivery device by using a thermoplastic polyurethane elastomer (TPU) material. TPU refers to a class of elastomeric block polymers containing repeating urethane functional groups in the macromolecular backbone, which has the greatest advantage over other raw materials that can be used for 3D printing in that their soft and hard segments are composed of different materials, which makes them both of high elasticity for rubber and high strength for plastics. In addition, the TPU material has excellent wear resistance, chemical resistance, bacteria resistance, biomedical compatibility, shape memory performance and the like compared with the like products, is an elastomer material with excellent comprehensive performance, and is particularly suitable for being used as a material of the novel drug delivery device.
Drawings
FIG. 1 is a graph showing the pH detection result of a sustained drug delivery apparatus prepared in example II of the present utility model.
Fig. 2 is a structural view of the sustained drug delivery device of the present utility model.
FIG. 3 is a schematic diagram of a sustained release apparatus according to the second embodiment of the present utility model.
Fig. 4 is a graph showing the length measurement result of the continuous administration device prepared in the second embodiment of the present utility model.
Fig. 5 is a graph showing the thickness measurement result of the sustained drug delivery device prepared in example two of the present utility model.
FIG. 6 is a diagram showing the placement of a continuous administration device in the eye of an experimental animal in an animal experiment according to the present utility model in comparison with the administration mode of an infusion set using a hose connection in the prior art.
FIG. 7 is a standard curve of the neonatal bovine serum as a matrix in an animal experiment of the present utility model.
FIG. 8 is a graph showing the drug concentration profile of the glass body sample in the time of the infraction An Nai De in the animal experiment of the present utility model.
FIG. 9 is a graph showing the concentration of the drug at An Nai De time from the infraffing aqueous humor sample in the animal experiment of the present utility model.
Detailed Description
In order to enable those skilled in the art to better understand the technical solution of the present utility model, the technical solution of the present utility model is further described below with reference to the accompanying drawings and examples.
Embodiment one:
an embodiment one provides a drug for treating an ocular disease, the drug being triamcinolone acetonide hydrogel; the triamcinolone acetonide hydrogel comprises the following components: succinic anhydride, triamcinolone acetonide, and pyridine.
The specific preparation method of the medicine for treating eye diseases comprises the following steps,
s1: preparing carbomer gel with the mass concentration of 2 percent: taking 0.2g of carbomer powder, shaking in a 15ml centrifuge tube containing 10ml of ultrapure water, shaking in a water bath at 60 ℃ for 10min, and uniformly mixing until the carbomer powder is homogeneous;
s2: co-dissolving triamcinolone acetonide gel and succinic anhydride, pyridine: 400mg of triamcinolone acetonide gel, 280mg of succinic anhydride and 10mL of pyridine were co-dissolved and stirred at room temperature for 3h.
S3: removing the organic solvent in the mixed solution obtained in the step S2, adding water, centrifuging and collecting fine crystals: removing the organic solvent with an evaporator, and adding 10mL of water; after stirring vigorously for 20 minutes, the flask was placed in a refrigerator and the fine crystals were collected by centrifugation and lyophilized for use.
S4: the fine crystals collected in step S3 were dissolved in PBS buffer solution having ph=7.4 to give a final concentration of 400mg/mL, and left at 37 ℃ for 35 hours to form triamcinolone acetonide hydrogel having a pH of 4 to 5 as shown in fig. 1.
Embodiment two:
a second embodiment provides a sustained delivery apparatus for treating an eye disease, the sustained delivery apparatus having a structure shown in fig. 2 and comprising a Tenon subcapsular implant 1; the Tenon subcapsular implant 1 consists of an arc body cavity structure 2 and wing-shaped fixing plates 3 arranged on two sides of the arc body cavity structure 2; the circular arc body cavity structure 2 is communicated with a medicine injection port 4 for injecting triamcinolone acetonide hydrogel.
Preferably, the continuous drug delivery device is prepared by a three-dimensional lithography (SLA) light curing forming technology in a 3D printing technology, and compared with other 3D printing technologies, the SLA light curing forming technology has the advantages of high processing speed, high forming precision, high surface smoothness, high material utilization rate and the like, and mainly uses liquid photosensitive resin as a raw material, and ultraviolet light with specific wavelength and intensity is focused on the surface of the liquid photosensitive resin to enable the ultraviolet light to be sequentially solidified from point to line and from line to surface, so that drawing of a layer section is completed. The specific preparation process comprises the following steps of,
step A:3D printing pretreatment, obtaining a digital model of the continuous drug administration device;
specifically, the method comprises three-dimensional modeling and obtaining a digital model, namely, rendering a virtual 3D model of a physical object by using a digital model of a Computer Aided Design (CAD) eye continuously controllable drug delivery device;
and (B) step (B): manufacturing a 3D model of the continuous drug administration device;
specifically, the steps include 3D printing and making into a real object, namely, cutting the obtained virtual model into a series of continuous transverse layers, converting the digital model into a standard surface subdivision language (STL) file readable by a 3D printer, transmitting data to the printer, utilizing the characteristic that liquid photosensitive resin can be quickly solidified under the irradiation of ultraviolet laser beams, using Godart 8228 resin to perform laser scanning printing in a high-precision Litai SLA printer, spraying the material layer by layer onto the three-dimensional space of a series of continuous transverse layers according to the layer thickness of 0.1mm, and finally making into the three-dimensional real object from the electronic digital model.
Step C: post-processing of the 3D model of the continuous drug administration device;
and B, taking out the model deposited on the printing platform in the step B, washing out uncured resin covered on the model by using an ultrasonic cleaner, removing the supporting structure by using a cutter, and then performing model surface painting process manufacturing to finish model curing.
Step D: and (3) laminating by using a TPU material to obtain the continuous drug delivery device for 3D printing.
And C, placing the model obtained after the post-treatment in the step C into a silica gel mold, then placing the model into a vacuum machine, injecting TPU material with the hardness of 50A-60A, and opening the mold after the silica gel mold is cooled to obtain the soft continuous eye administration device.
The TPU material selected in this experiment was DPI8400 and its relevant performance characteristics are shown in Table 1 below. DPI8400 has the advantages of low viscosity, good fluidity, fast curing, good elasticity and the like, and the hardness can be adjusted at will by controlling the relevant amount within the range of Shore A20-90. Shore refers to Shore hardness, a standard for evaluating material hardness, where Shore A is used to test soft plastic, elastomer and rubber materials. Examples of different hardness materials are shown in table 2 below. Because the hardness of the TPU material is smaller and the shrinkage rate is larger, the DPI8400 is prepared into the 50A hardness, the increase of the size error rate in the model materialization process caused by the shrinkage rate is avoided, and meanwhile, the drug delivery device after the model is subjected to model resetting has good flexibility and certain toughness and ductility, namely, the drug delivery device can be implanted under the Tenon's capsule of the rabbit eye through folding and naturally extend to recover the original shape, tissue anaphylactic reaction and local stimulation are not easy to cause, and the risks of toxicity and adverse reaction are reduced.
TABLE 1TPU Material Properties specific
Table 2 different shore a hardness examples references
The sustained delivery apparatus prepared by this example, which had good softness as shown in fig. 3, was measured for length and thickness as shown in fig. 4 and 5, respectively, and as can be seen from fig. 4 and 5, for a length of about 5cm and a thickness of about 0.8cm.
Animal experiment:
the animal experiment was performed using the triamcinolone acetonide gel prepared in example one and the continuous administration device prepared in example two, and the specific process of the animal experiment includes the following steps:
1. grabbing rabbits, weighing, intramuscular injection Liu Mianning according to the dosage of 0.15ml/kg, then intravenous injection of a proper amount Liu Mianning at the edge of the ear, and test the cornea reflection of the rabbits while injection to evaluate the anesthesia depth, wherein the intravenous injection of 0.15ml Liu Mianning at the edge of the ear is approximate;
2. in the process of waiting for anesthesia, the levofloxacin eye drops are used for dropping eyes 5 times; eye-pointing for 5 times by ai' er Kain;
3. after the rabbit enters an anesthetic state, fully exposing the eyeball by using an eyelid retractor, flushing a conjunctival sac by using a syringe to take 1ml of Aneriodo III, and flushing by using normal saline after 30 s;
4. making an incision at a position which is about 3mm away from the limbus at a position of 9-11 points between the upper rectus muscle and the lower rectus muscle, carefully and passively separating the two muscles by using hemostats, and separating the Tenon capsule as far as possible by using ophthalmic scissors so that the drug delivery device has enough space to be placed;
5. the two butterfly wings of the drug delivery device are arranged below two rectus muscles, as shown in the A of the figure 6, the body of the drug delivery device is stuffed under the Tenon bag, as shown in the B of the figure 6, the C of the figure 6 shows a schematic diagram of the current clinical application of a hose connected intravenous infusion set, the drug delivery mode needs to be fixed under the temporal bulbar conjunctiva through a suture, as shown in the D of the figure 6, and needs to be connected with an automatic drug delivery pump, as shown in the E of the figure 6, therefore, compared with the prior design, the utility model is easier to carry out minimally invasive surgical implantation, is small and portable, and the two butterfly wings of the drug delivery device are implanted below the two rectus muscles, and is fixed by the force of the rectus muscles and is not easy to shift and deviate; the body is stuffed under the Tenon's capsule, so that the plane of the grid holes on which the medicine is oozed can be attached to the surface of the sclera to the greatest extent, the medicine can be directly contacted with the surface of the sclera after oozing from the grid holes, the administration path of the medicine across the sclera is shortened, the medicine quantity directly attached to the surface of the sclera is increased, the residence time of the medicine on the surface of the sclera is prolonged, a foundation is provided for better penetration and absorption of the medicine across the sclera and reaching the effective medicine concentration, the slow release effect of the triamcinolone acetonide medicine is realized through hydrogel, the bioavailability of the medicine is improved, and the medicine is stably and permanently in the intraocular tissue to reach the effective treatment concentration. The drug is released in the body to avoid the drug contacting the conjunctiva, thereby being absorbed by blood vessels and tissues of the conjunctiva, preventing excessive drug from entering the blood circulation and bringing about systemic side effects.
6. Filling fullness of the drug delivery device was observed by injecting 1ml of 40mg/ml triamcinolone acetonide gel into the head of the drug delivery device using a 1ml syringe;
7. suturing the conjunctiva;
8. the levofloxacin eye drops are used for dropping eyes, and the time is once every 5min, and the total time is 3 times;
9. after 7 days of administration, 2-5ml of blood is drawn from the auricular artery, and the blood is respectively taken by a common red head blood taking tube and an EDTA anticoagulation blood taking tube, the red head blood taking tube is kept stand at room temperature for 2 hours, and the red head blood taking tube is immediately put at 4 ℃ for temporary storage. After the foam box and the ice bag are transported back to the laboratory, serum and plasma are collected respectively according to the following steps and stored at-80 ℃.
(1) LC-MS metabolic plasma sample collection:
collecting 2-5mL peripheral blood in a blood collection tube without any additive (except anticoagulant), slightly reversing and shaking uniformly (not shaking vigorously to prevent hemolysis), standing at 4 ℃ or in an ice bath for about 10min, centrifuging at low temperature (3000 rpm,10min,4 ℃) firstly, taking most of upper plasma, centrifuging at high speed (12000 rpm,10min,4 ℃), and taking the rest small amount of upper plasma; if hemolysis is not available, 200 mu L of the solution is packaged, and the solution is frozen in liquid nitrogen for 15min and stored at-80 ℃.
(2) Serum sample collection:
whole blood specimens were left at room temperature for 2 hours, and then the cores were separated at 3000rpm at 2-8℃for 15 minutes, and the supernatant was collected.
10. The animals were sacrificed by intravenous injection of 20ml of air into the ear margin after blood collection;
11. washing bulbar conjunctiva and conjunctival sac with physiological saline, and washing off residual liquid medicine and blood on ocular surface;
12. taking 3 tissue samples along 11-12 points ((1)), 8-10 points ((2)) in the middle and 6-7 points ((3)) in the lower part of the drug delivery device, flushing with physiological saline, fixing to 3ml of 4% paraformaldehyde, and storing in a refrigerator at 4 ℃;
13. confirm that the drug delivery device is still below rectus muscle;
14. removing the right eyeball, and observing the residual quantity of triamcinolone acetonide carbomer gel medicine of the medicine administration device and the adhesion condition of the medicine administration device and surrounding tissues;
15. pouring a proper amount of physiological saline into the disposable urine cup, placing the eyeball into the urine cup, clamping the eyeball by forceps, shaking the eyeball back and forth for a plurality of times, and removing the residual liquid medicine on the surface of the eyeball; dipping the eyeball with clean gauze, placing the eyeball in another 1 clean urine cup, taking a proper amount of physiological saline by using a syringe, and dipping the eyeball with the clean gauze;
16. horizontally puncturing the limbus at 1.5mm position inside the limbus with a 1ml syringe to obtain about 0.1-0.2ml aqueous humor, storing at-20deg.C, transporting back to research institute, storing at-80deg.C, and determining triamcinolone acetonide gel drug concentration in aqueous humor;
17. directly puncturing the sclera with a 2.5ml syringe to extract vitreous humor in a 1.5ml centrifuge tube, storing at-20deg.C, transporting back to the research institute, and storing at-80deg.C to determine triamcinolone acetonide gel drug concentration in the vitreous;
18. separating and stripping the retinochoroidal tissues by using ophthalmic toothed forceps and a small-size medicine spoon, placing the retinochoroidal tissues in a 1.5ml centrifuge tube, storing at-20 ℃, and storing at-80 ℃ after transporting back to a research institute to determine the concentration of triamcinolone acetonide gel medicine in the retinochoroid.
Further, the vitreous humor sample obtained in operation 17 was subjected to detection treatment, and 1-L8 and Trim-LQC, trim-MQC, trim-HQC, and 200. Mu.L of the sample to be tested were added to a 96-well plate (centrifuged at 14000rpm for 10min before sampling the sample to be tested), diluted with 200. Mu.L of purified water, and subjected to sample analysis.
Performing a test treatment on the serum sample obtained in operation 9, the aqueous humor sample obtained in operation 16, and the retinal sample obtained in operation 18: adding L1-L8, trim-LQC, trim-MQC, trim-HQC and 50 mu L of a sample which take new-born calf serum as a matrix into a 2mL transparent centrifuge tube, adding 350 mu L of dichloromethane for liquid-liquid extraction, centrifuging for 5min at a speed of 14000rpm after vortex for 5min, transferring 300 mu L of an organic layer into a 96-well plate for nitrogen blowing concentration, adding 100 mu L of 0.1% methanolic formate for redissolution, and carrying out sample analysis.
The standard curve with neonatal bovine serum as matrix is shown in fig. 7, linear range: 5-1000 ng/Ml, can be used for quantifying aqueous humor, serum and retina samples
The triamcinolone acetonide time drug concentration curve in the vitreous body sample is shown in fig. 8, the orange line is the drug concentration curve, and the blue is the time point; as can be seen from FIG. 8, the concentration of triamcinolone acetonide in the vitreous cavity of the rabbit eye after the transscleral drug administration device was placed for 30 minutes had a peak concentration of 175 ng/mL and the concentration of the drug in the vitreous cavity was maintained at 161ng/mL after 1 hour, the concentration of triamcinolone acetonide in the vitreous cavity had a lower level of 59.8 ng/mL after 6 hours, the concentration of triamcinolone acetonide again had a peak of 166 ng/mL after 24 hours, and the concentration of the drug in the vitreous cavity had been reduced to 23.93-35..10ng/mL for about 1 week to two weeks after administration, and the average concentration of the drug in the vitreous cavity was 100.66ng/mL.
As shown in FIG. 9, the concentration curve of triamcinolone acetonide in the waterproof sample is shown in FIG. 9, the concentration of triamcinolone acetonide in aqueous humor of rabbit eye is kept at about 500 ng/mL for 30 minutes to 6 hours after the transscleral drug administration device is placed, and peak value appears in the concentration of triamcinolone acetonide in aqueous humor after 12 hours, which is 763ng/mL, the concentration of triamcinolone acetonide in aqueous humor after 24 hours is slightly reduced to 640.67ng/mL, the concentration of triamcinolone acetonide in aqueous humor after 1 week is reduced to 108.60ng/mL after 2 weeks, and the concentration of triamcinolone acetonide in aqueous humor is reduced to 19.10ng/mL.
The foregoing has shown and described the basic principles, principal features and advantages of the utility model. It will be understood by those skilled in the art that the present utility model is not limited to the embodiments described above, and that the above embodiments and descriptions are merely illustrative of the principles of the present utility model, and various changes and modifications may be made without departing from the spirit and scope of the utility model, which is defined in the appended claims. The scope of the utility model is defined by the appended claims and equivalents thereof.
Claims (9)
1. A medicament for the treatment of an ocular disorder, characterized in that: the medicine is triamcinolone acetonide hydrogel; the triamcinolone acetonide hydrogel comprises the following components: succinic anhydride, triamcinolone acetonide, and pyridine.
2. The method for producing a drug for the treatment of ocular diseases as claimed in claim 1, comprising the steps of,
s1: centrifuging and air-drying 400mg/ml triamcinolone acetonide suspension to obtain triamcinolone acetonide powder;
s2: co-dissolving triamcinolone acetonide powder, succinic anhydride and pyridine;
s3: removing the organic solvent in the mixed solution obtained in the step S2, adding water, centrifuging and collecting fine crystals;
s4: the fine crystals collected in step S3 were dissolved in PBS buffer solution and left at 37℃for 1-2 days to form triamcinolone acetonide hydrogel.
3. The method for preparing a drug for the treatment of ocular diseases according to claim 2, wherein the specific procedure of step S2 comprises the steps of co-dissolving 400mg triamcinolone acetonide powder, 280mg succinic anhydride and 10mL pyridine and stirring at room temperature for 3-4h.
4. The method for preparing a medicament for the treatment of ocular diseases according to claim 2, wherein the specific operation steps of step S4 comprise: the fine crystals collected in step S3 were dissolved in PBS buffer solution having ph=7.4 to give a final concentration of 400mg/mL, and left at 37 ℃ for 35 hours to form triamcinolone acetonide hydrogel.
5. A sustained drug delivery device for the treatment of ocular disorders, characterized in that: the sustained drug delivery device includes a Tenon subcapsular implant; the Tenon subcapsular implant consists of an arc body cavity structure and wing-shaped fixing plates arranged on two sides of the arc body cavity structure; the circular arc body cavity structure is communicated with a medicine injection port for injecting the medicine according to claim 1, and the continuous medicine feeding device is prepared through 3D printing.
6. The method for producing a sustained-administration device for an ophthalmic disease treatment drug according to claim 5, comprising the steps of,
step A:3D printing pretreatment, obtaining a digital model of the continuous drug administration device;
and (B) step (B): manufacturing a 3D model of the continuous drug administration device;
step C: post-processing of the 3D model of the continuous drug administration device;
step D: and (3) laminating by using a TPU material to obtain the continuous drug delivery device for 3D printing.
7. The method for preparing a sustained-release apparatus for treating an ocular disease according to claim 6, wherein the specific operation of step B comprises the steps of "cutting" the digital model of the sustained-release apparatus of step a into a series of continuous transverse layers, converting the digital model into a standard tessellation language file readable by a 3D printer, transmitting the data to the printer, laser scanning and printing in the printer using a resin material, and spraying the material layer by layer onto a three-dimensional space of a series of continuous transverse layers according to a layer thickness of 0.1mm, thereby finally producing a three-dimensional object.
8. The method for preparing a sustained release apparatus for treating an ocular disease as claimed in claim 6, wherein the specific operation of the step C comprises the steps of taking out the mold deposited on the printing table in the step B, washing off uncured resin covered on the mold with an ultrasonic cleaner, removing the supporting structure with a cutter, and performing a mold surface painting process to complete the mold curing.
9. The method for preparing a sustained-release apparatus for treating an ocular disease according to claim 6, wherein the specific operation of step D comprises the steps of injecting silica gel into a silica gel cavity to prepare a silica gel mold, placing the mold obtained after the post-treatment of step C into the silica gel mold, then placing into a vacuum machine, injecting a TPU material having a hardness of 50A to 60A, and opening the mold after the silica gel mold is cooled to obtain the soft sustained-release apparatus for an ocular disease.
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