Drug-loaded contact lens and preparation method thereof

Abstract

The invention discloses a drug-loaded contact lens and a preparation method thereof, and the preparation method comprises the following steps: dissolving a drug in a mixed solution of a surfactant, a cosurfactant and deionized water to prepare a drug microemulsion; the preparation method comprises the following steps: uniformly mixing a silicon monomer, a hydrophilic monomer, a cross-linking agent and an initiator by ultrasonic waves, and carrying out compression molding, photopolymerization or thermal polymerization and demolding to obtain the contact lens, and soaking the contact lens in the drug microemulsion to obtain the drug-loaded contact lens. The maximum drug loading capacity of the contact lens is 215.17 to 217.47 [mu] g / lens. The drug microemulsion prepared by the method is uniform in particle size and stable in morphology. The contact lens can efficiently load the medicine, the bioavailability of the medicine is improved, the basic performance of the medicine-loaded contact lens is stable, and the wearing comfort is improved; the prepared drug microemulsion not only has uniform particle size and stable morphology, but also can effectively reduce the surface contact angle of contact lenses.

Description

Technical Field

[0001] The invention relates to the field of drug loading, in particular to a drug-loaded contact lens and a preparation method thereof. Background Art

[0002] Keratitis is one of the most common eye diseases, with pain, photophobia and tearing as the main symptoms. Keratitis is usually caused by bacteria, viruses, fungi or other microbial infections. About 50% of eye keratitis is related to infection, of which about 80% is bacterial keratitis. Keratitis may cause vision loss or even blindness in patients, which is a serious threat to human health.

[0003] The traditional method of treating keratitis is drip administration. Since the drug cannot directly reach the deep cornea through the cornea, it can only form a drug film on the surface of the cornea, resulting in insufficient local drug concentration and utilization rate of less than 5%. As a carrier of ophthalmic drug molecules, contact lenses can effectively improve the bioavailability and efficacy of drugs and improve patient compliance, and have broad application prospects.

[0004] Drug delivery methods for contact lenses include direct immersion, vitamin E as a diffusion barrier, colloidal nanoparticles, molecular imprinting, and supercritical impregnation. These methods can greatly increase the drug loading of contact lenses, but they will also affect the basic properties of contact lenses such as transmittance, contact angle, oxygen permeability, and mechanical properties, which will affect the practical application of contact lenses in the field of ophthalmology.

[0005] Fluoroquinolone antibiotics kill bacteria mainly by inhibiting the biosynthesis of bacterial proteins. Fluconazole can effectively inhibit the synthesis of major steroid substances on fungal cell membranes, reduce the stability of cell membranes, and lead to fungal death. Ribavirin blocks the replication process of multiple RNA virus-infected cells by interfering with RNA synthesis, thereby inhibiting or eliminating infection. It is used to treat keratitis.

[0006] At present, there is no method that can achieve high drug loading while maintaining the stability of its basic performance after drug loading; in addition, the existing drug-loaded contact lenses can easily cause corneal hypoxia if worn for a long time, have poor hydrophilicity, and have a complicated process and are not environmentally friendly. Summary of the invention

[0007] Purpose of the invention: In order to overcome the deficiencies in the prior art, the purpose of the present invention is to provide a simple, convenient, green and environmentally friendly method for preparing drug-loaded contact lenses. Another purpose of the present invention is to provide a drug-loaded contact lens with efficient drug loading, stable basic performance and good bactericidal effect on Escherichia coli.

[0008] Technical solution: The method for preparing a drug-loaded contact lens of the present invention comprises the following steps:

[0009] Step 1, dissolving the drug in a mixed solution of a surfactant, a co-surfactant and deionized water to prepare a drug microemulsion;

[0010] Step 2, uniformly mixing the silicon monomer, the hydrophilic monomer, the crosslinking agent and the initiator by ultrasonication, and obtaining the contact lens by compression molding, photopolymerization or thermal polymerization, and demolding;

[0011] Step three, immersing the contact lens in the drug microemulsion to obtain the drug-loaded contact lens.

[0012] Furthermore, in step 1, the drug is one or more of levofloxacin, moxifloxacin, ofloxacin, ciprofloxacin, nalidixic acid, pipemidic acid, norfloxacin, enoxacin, lomefloxacin, pefloxacin, sparfloxacin, tobramycin, fluconazole, itraconazole, and ribavirin; and the concentration of the drug microemulsion is 1 to 20 mg / mL, preferably 1 to 10 mg / mL.

[0013] Furthermore, in step one, the surfactant is polyoxyethylene fatty alcohol ether (Tween series) or tetradecyl sulfopropyl betaine, and the co-surfactant is one or more of ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol, and isopentanol.

[0014] Furthermore, in step 1, the volume ratio of the surfactant, the co-surfactant and the deionized water is 2-6:1-3:2-5, and the volume ratio is preferably 3-5:1.5-3:2-4.

[0015] Furthermore, in step 2, the silicon monomer is one or more of polydimethylsiloxane terminated with methacrylate (IEM), polydimethylsiloxane terminated with hydroxyethyl methacrylate (HEMA), polydimethylsiloxane terminated with glycidyl methacrylate (GMA), methacryloxypropyl tris(trimethylsiloxy)silane (TRIS), γ-aminopropyltriethoxysilane (KH-550), γ-(methacryloxy)propyltrimethoxysilane (KH-570), and propylglycerol methacrylate di(trimethylsiloxy)methylsilane (SIGMA).

[0016] Furthermore, in step 2, the hydrophilic monomer is one or more of N-vinyl pyrrolidone (NVP), hydroxypropyl methacrylate (HPMA), N,N-dimethylacrylamide (DMA), β-hydroxyethyl methacrylate (HEMA), acrylic acid (AA), acrylamide (AM), methyl methacrylate (MMA), N-vinyl-N-methylacetamide (VMA), isocyanoethyl methacrylate (IEM), polyether polyol, 2-methacryloyloxyethyl dimethyl 3-sulfonate propyl ammonium hydroxide (SBMA), and 2-methacryloyloxyethyl phosphorylcholine (MPC).

[0017] Furthermore, in step 2, the crosslinking agent is one or more of ethylene glycol dimethacrylate (EGDMA), diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, polyethylene glycol diacrylate, and glycerol trimethacrylate.

[0018] Further, in step 2, the initiator is a photoinitiator or a thermal initiator, the photoinitiator is 2-hydroxyisobutyrophenone (D-1173), 2-hydroxy-2-methyl-1-phenyl ketone, 1-hydroxy-cyclohexyl phenyl ketone, 4-phenylbenzophenone, methyl o-benzoylbenzoate or more, the thermal initiator is azobisisobutyronitrile (AIBN), azobisisoheptanenitrile, benzoyl peroxide (BPO), di-tert-butyl peroxide (DTBP), diisopropylbenzene peroxide (DCP), tert-butyl hydroperoxide (TBHP), 2,2-azobis(2-methylpropionamidine) dihydrochloride or more.

[0019] Furthermore, in step 2, the mass ratio of silicon monomer, hydrophilic monomer, crosslinking agent and initiator is 10-88:10-40:0.5-1:0.5-1, preferably 30-88:20-40:0.5-0.8:0.5-0.8.

[0020] Further, in step 2, at 160-180V, 10-30mW / cm 2 The prepolymerized monomers are subjected to photopolymerization for 30 to 90 minutes under the following conditions, or are thermally polymerized in a constant temperature water bath at 60 to 90° C. for 30 to 90 minutes, and then immersed in a 10 vol % to 30 vol % ethanol aqueous solution for 1 to 48 hours to remove unreacted monomers.

[0021] Furthermore, in step three, the soaking period is 1 to 7 days.

[0022] The drug-loaded contact lens of the present invention has a maximum drug loading of 215.17 to 217.47 μg / lens.

[0023] Preparation principle: In the first step, the molecular structure of quinolone antibiotics contains a quinolone nucleus and some specific functional groups. The quinolone nucleus has a certain hydrophobicity, and some polar groups (carboxyl groups) in the molecule make it hydrophilic. This amphiphilic structure makes it have different solubility and distribution behaviors in different environments. The surfactant molecules of the microemulsion have a hydrophilic head and a hydrophobic tail, which can form a micellar structure in the solution. The co-surfactant can reduce the interfacial tension of the surfactant, making it easier to form micelles. Due to the amphiphilicity of the quinolone antibiotic molecule, it can be solubilized into the micellar structure of the microemulsion. The hydrophobic core of the micelle can accommodate the hydrophobic part of the quinolone antibiotic molecule, while the hydrophilic head is in contact with the water phase. This solubilization effect can greatly increase the concentration of levofloxacin in the solution, thereby laying the foundation for the subsequent increase in the drug loading of the contact lens. Because when the contact lens is immersed in the drug microemulsion, the high concentration of the drug is more easily adsorbed or absorbed by the contact lens.

[0024] In the second step, silicone hydrogel is a polymer material formed by the polymerization of silicone monomers, hydrophilic monomers, crosslinking agents and initiators. The introduction of silicone monomers increases the gas permeability of the material, while hydrophilic monomers give the material a certain hydrophilicity. The crosslinking agent forms a crosslinked network between polymer molecules, which increases the mechanical strength of the material. This special chemical structure makes silicone hydrogel contact lenses have good gas permeability, hydrophilicity and mechanical properties. When the contact lens is immersed in a drug microemulsion, the hydrophilic surface is more likely to adsorb the microemulsion droplets containing the drug. When the drug molecules enter the contact lens, the crosslinking structure can bind the drug molecules in it through physical adsorption or intermolecular forces.

[0025] In the third step, during the immersion process, levofloxacin in the microemulsion diffuses into the contact lens. Due to the hydrophilicity and cross-linked structure of the silicone hydrogel contact lens, it can produce multiple interactions with the drug molecules in the microemulsion. Both the gaps and hydrophilic regions in the cross-linked structure may become storage sites for drug molecules. This multi-site storage method can increase the drug loading capacity of the contact lens, so that under the same immersion conditions, more drug molecules can be loaded into the contact lens, thereby increasing the drug loading.

[0026] Beneficial effects: Compared with the prior art, the present invention has the following significant features:

[0027] 1. The obtained contact lenses can achieve high drug loading while maintaining stable basic performance after drug loading. The contact lenses provide the first barrier for drug transport, and the oil-water interface of the microemulsion provides the second barrier for drug release. In the drug immersion solution with the same concentration, the drug loading of the contact lenses prepared by the microemulsion method is increased by 51.65% compared with the direct immersion method, and the maximum drug loading is 216.32±1.15μg / lens (p>0.05), which greatly improves the bioavailability of the drug;

[0028] 2. The prepared drug microemulsion not only has uniform particle size and stable morphology, but also can effectively reduce the contact angle of the contact lens surface, improve wearing comfort, has high oxygen permeability and high hydrophilicity, and the hydrophilic monomers are more diverse;

[0029] 3. The drugs used can treat infectious eye diseases such as keratitis;

[0030] 4. The drug-loaded contact lenses have lower contact angles, higher transmittance, stable mechanical properties, good bactericidal effects on Escherichia coli and Staphylococcus aureus, and can effectively load drugs;

[0031] 5. The introduction of microemulsion can effectively improve the hydrophobic properties of silicone-based hydrogel and better meet the wearing requirements;

[0032] 6. The preparation method is simple, easy to operate, green and environmentally friendly, and has broad market application prospects as a therapeutic contact lens. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is a particle size distribution diagram of the levofloxacin microemulsion prepared in Example 1 of the present invention;

[0034] Figure 2 is a particle size distribution diagram of the levofloxacin microemulsion prepared in Example 2 of the present invention;

[0035] Figure 3 is the cumulative release graph of levofloxacin;

[0036] Figure 4 It is a sterilization diagram of contact lenses loaded with levofloxacin;

[0037] Figure 5 Graphs of the surface contact angles of contact lenses before and after drug loading, where (a) is before drug loading and (b) is after drug loading. DETAILED DESCRIPTION

[0038] The materials, reagents, instruments, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources. The experimental methods without specific conditions in the examples are usually carried out under conventional conditions or under conditions recommended by the manufacturer. The average molecular weight of IEM-terminated polydimethylsiloxane is 8000, the average molecular weight of HEMA-terminated polydimethylsiloxane is 5000, and the average molecular weight of GMA-terminated polydimethylsiloxane is 5000.

[0039] Example 1

[0040] A method for preparing a drug-loaded contact lens comprises the following steps:

[0041] S1. Preparation of drug microemulsion:

[0042] Surfactant Tween20, co-surfactant isopropyl alcohol (IPA), and deionized water were mixed in a volume ratio of 47.05 vol%, 23.53 vol%, and 29.42 vol%, respectively, and levofloxacin was added to the mixed solution, and ultrasonic mixing was performed to prepare a drug microemulsion with a concentration of 4.8 mg / mL, which was coded as LVF-ME-1. The particle size of LVF-ME-1 measured by wide-angle laser light scattering instrument is as follows Figure 1 As shown, the particle size of LVF-ME-1 is 160.47±32.16nm. The particle size distribution of the microemulsion is uniform, with a diameter range of about 160nm, and there is no aggregation phenomenon.

[0043] S2. Preparation of contact lenses:

[0044] The polydimethylsiloxane terminated with silicon monomer IEM, hydrophilic monomer AA, crosslinking agent ethylene glycol diacrylate and photoinitiator 1-hydroxy-cyclohexyl phenyl ketone were mixed in a mass ratio of 65wt%, 34wt%, 0.5wt% and 0.5wt% respectively, and ultrasonically dissolved to obtain a prepolymerized monomer. The bubbles were removed by ultrasonic dissolution in the dark. 40μL of the prepolymerized monomer was transferred into a polypropylene mold and heated at 175V, 13mW / cm 2 The contact lens was removed from the mold and immersed in a 15 vol% ethanol aqueous solution for 24 hours to remove unreacted monomers.

[0045] S3. Soak the contact lens in the levofloxacin microemulsion obtained in step S1 for 1 day to obtain a drug-loaded contact lens, which is coded as LVF-ME-SCL-1.

[0046] The equilibrium water content of the drug-loaded contact lens obtained in this example was 44.58±0.66% (p>0.05), the transmittance was 95.34±0.32% (p>0.05), and the contact angle was 34.66±0.30° (p>0.05).

[0047] Example 2

[0048] A method for preparing a drug-loaded contact lens comprises the following steps:

[0049] S1. Preparation of drug microemulsion:

[0050] Surfactant Tween20, co-surfactant isopropanol, and deionized water were mixed in a volume ratio of 47.05 vol%, 23.53 vol%, and 29.42 vol%, respectively, and levofloxacin was added to the mixed solution, and ultrasonic mixing was performed to prepare a drug microemulsion with a concentration of 5.3 mg / mL, which was coded as LVF-ME-2. The particle size of LVF-ME-2 measured by wide-angle laser light scattering instrument is as follows Figure 1 As shown, the particle size of LVF-ME-1 is 162.51±42.69nm. The particle size distribution of the microemulsion is uniform, with a diameter range of about 160nm, and there is no aggregation phenomenon.

[0051] S2. Preparation of contact lenses:

[0052] The polydimethylsiloxane terminated with silicon monomer IEM, hydrophilic monomer AM, crosslinking agent trimethacrylate glycerol and photoinitiator methyl o-benzoylbenzoate were mixed in a mass ratio of 65wt%, 34wt%, 0.5wt% and 0.5wt%, respectively, and ultrasonically dissolved to obtain a prepolymerized monomer. The bubbles were removed by ultrasonic dissolution in the dark. 40μL of the prepolymerized monomer was transferred into a polypropylene mold and heated at 175V, 13mW / cm 2 The contact lens was removed from the mold and immersed in a 15 vol% ethanol aqueous solution for 24 hours to remove unreacted monomers.

[0053] S3. Soak the contact lens in the levofloxacin microemulsion obtained in step S1 for 1 day to obtain a drug-loaded contact lens, which is coded as LVF-ME-SCL-2.

[0054] The equilibrium water content of the drug-loaded contact lens obtained in this example was 45.38±0.54% (p>0.05), the transmittance was 93.56±0.15% (p>0.05), and the contact angle was 33.13±0.67° (p>0.05).

[0055] Comparative Example 1

[0056] 9.6 mg of levofloxacin was dissolved in 2 mL of artificial tears to prepare 2 mL of 4.8 mg / mL levofloxacin-artificial tears. The contact lenses were then soaked in 2 mL of 4.8 mg / mL levofloxacin-artificial tears, coded as LVF-SM-SCL.

[0057] Performance Test:

[0058] 1. Drug sustained release behavior of drug-loaded contact lenses in artificial tears

[0059] The contact lens loaded with levofloxacin was immersed in 2 mL of artificial tear release medium. At each sampling time interval, 1 mL of sample was taken for drug release experiment, and 1 mL of fresh artificial tears was used to replace the initial 1 mL of artificial tear release medium. The ultraviolet absorption of the solution at 287 nm was calculated by ultraviolet spectrophotometer, and the cumulative release of levofloxacin was calculated by comparing with the standard curve. The experimental results are shown in Figure 2. Figure 3 As shown. In the levofloxacin solution of the same concentration, the cumulative release of levofloxacin in the LVF-ME-SCL-1 group obtained in Example 1 increased by 51.65% compared with the LVF-SM-SCL group obtained in Comparative Example 1. The cumulative release of levofloxacin in the LVF-ME-SCL-2 group obtained in Example 2 was the highest, which was 216.32±1.15μg / lens (p>0.05), which greatly improved the utilization of the drug. The presence of the microemulsion effectively reduced the interfacial tension of oil and water, improved the thermodynamic stability of the levofloxacin microemulsion, and allowed more levofloxacin to be adsorbed on the surface or pores of the contact lens, increasing the loading rate of levofloxacin. The maximum drug loading of the contact lenses prepared by this method meets the daily dosage of disposable contact lenses.

[0060] 2. In vitro sterilization behavior of drug-loaded contact lenses

[0061] Escherichia coli and Staphylococcus aureus were inoculated into Luria-Bertani agar medium, and the inoculated bacterial solution was cultured on a 37°C constant temperature shaker for 12 hours. Take two 24-well plates and add 2 mL of OD 600=0.1. Among them, only E. coli solution was added to the first column of the first well plate, E. coli solution and levofloxacin-loaded contact lenses prepared by direct immersion method were added to the second column, and E. coli solution and levofloxacin microemulsion-loaded contact lenses were added to the third column, which were marked as Control, LVF-SM-SCL, and LVF-ME-SCL-1, respectively. In the same way, Staphylococcus aureus was added to another well plate and marked in the same way. After adding the bacterial solution and the drug-loaded contact lenses, the two interacted for 4-6 hours. Afterwards, the bacterial solution was diluted 1000 times, and 50 μL of the bacterial solution was put into the culture dish. The coated agar plate was placed in a constant temperature and humidity incubator for overnight culture. After the colonies have grown for a period of time, the colonies are counted under appropriate lighting conditions. The experimental results are as follows Figure 4 As shown, compared with the control group, the survival rate of Escherichia coli in the LVF-SM-SCL group and the LVF-ME-SCL-1 group was 0, and the survival rate of Staphylococcus aureus was 11.66±0.02% (p<0.0001) and 19.33±0.02% (p<0.0001), respectively. Compared with Staphylococcus aureus, the bactericidal effect of LVF-SM-SCL and LVF-ME-SCL-1 on Escherichia coli was more significant.

[0062] 3. Surface contact angle of levofloxacin-loaded contact lenses

[0063] The contact angle of the contact lens before and after drug loading was measured using a contact angle meter. Figure 5 As shown, the surface contact angle of the contact lens after drug loading was 32.88±1.19° (p>0.05), and the contact angle of the contact lens before drug loading was 104.33±2.51° (p>0.05), which shows that levofloxacin microemulsion can effectively reduce the contact angle of the contact lens, and keeping the contact lens moist can improve wearing comfort.

[0064] Example 3

[0065] A method for preparing a drug-loaded contact lens comprises the following steps:

[0066] S1. Preparation of drug microemulsion:

[0067] The surfactant tetradecyl sulfopropyl betaine, the co-surfactant ethanol and deionized water were mixed in volume proportions of 20 vol%, 10 vol% and 50 vol%, respectively, and then moxifloxacin was added to the mixed solution, and ultrasonic mixing was performed to prepare a drug microemulsion with a concentration of 1 mg / mL.

[0068] S2. Preparation of contact lenses:

[0069] The polydimethylsiloxane terminated with silicon monomer HEMA, the hydrophilic monomer NVP, the crosslinking agent EGDMA and the photoinitiator D-1173 were mixed in a weight ratio of 58wt%, 40wt%, 1wt% and 1wt% respectively, and ultrasonically dissolved to obtain a prepolymerized monomer. The bubbles were removed by ultrasonic dissolution in the dark. 40μL of the prepolymerized monomer was transferred into a polypropylene mold and heated at 160V, 10mW / cm 2 The contact lens was removed from the mold and immersed in a 15 vol% ethanol aqueous solution for 24 hours to remove unreacted monomers.

[0070] S3, soaking the contact lens in the levofloxacin microemulsion obtained in step S1 for 7 days to obtain a drug-loaded contact lens.

[0071] The equilibrium water content of the drug-loaded contact lens obtained in this example was 43.57±0.31% (P>0.05), the transmittance was 92.77±0.46% (p>0.05), and the contact angle was 36.51±0.69° (p>0.05).

[0072] Example 4

[0073] A method for preparing a drug-loaded contact lens comprises the following steps:

[0074] S1. Preparation of drug microemulsion:

[0075] The surfactant tetradecyl sulfopropyl betaine, the co-surfactant n-propanol and deionized water were mixed in volume proportions of 60 vol%, 20 vol% and 20 vol%, respectively, and ofloxacin was added to the mixed solution, and ultrasonic mixing was performed to prepare a drug microemulsion with a concentration of 20 mg / mL.

[0076] S2. Preparation of contact lenses:

[0077] The polydimethylsiloxane terminated with silicon monomer GMA, the hydrophilic monomer HPMA, the crosslinking agent dimethacrylate diethylene glycol ester and the photoinitiator 2-hydroxy-2-methyl-1-phenyl ketone were mixed in a mass ratio of 88wt%, 10wt%, 1wt% and 1wt%, respectively, and ultrasonically dissolved to obtain a prepolymerized monomer. The bubbles were removed by ultrasonic dissolution in the dark. 40μL of the prepolymerized monomer was transferred into a polypropylene mold and heated at 180V, 30mW / cm 2 The contact lens was removed from the mold and immersed in a 15 vol% ethanol aqueous solution for 24 hours to remove unreacted monomers.

[0078] S3, soaking the contact lens in the levofloxacin microemulsion obtained in step S1 for 4 days to obtain a drug-loaded contact lens.

[0079] The equilibrium water content of the drug-loaded contact lens obtained in this example was 45.14±0.54% (p>0.05), the transmittance was 94.10±0.92% (p>0.05), and the contact angle was 31.65±0.28° (p>0.05).

[0080] Example 5

[0081] A method for preparing a drug-loaded contact lens comprises the following steps:

[0082] S1. Preparation of drug microemulsion:

[0083] Surfactant Tween 20, co-surfactant n-butanol and deionized water were mixed in volume proportions of 30 vol%, 30 vol% and 40 vol%, respectively, and ciprofloxacin was added to the mixed solution, and ultrasonic mixing was performed to prepare a drug microemulsion with a concentration of 10 mg / mL.

[0084] S2. Preparation of contact lenses:

[0085] Silicon monomer KH-550, hydrophilic monomer DMA, crosslinking agent ethylene glycol diacrylate and thermal initiator AIBN were mixed in a mass ratio of 78.4wt%, 20wt%, 0.8wt% and 0.8wt%, respectively, and thermally polymerized in a constant temperature water bath at 90°C for 30 minutes, and then immersed in a 10vol% ethanol aqueous solution for 48 hours to remove unreacted monomers.

[0086] S3, soaking the contact lens in the levofloxacin microemulsion obtained in step S1 for 2 days to obtain a drug-loaded contact lens.

[0087] The equilibrium water content of the drug-loaded contact lens obtained in this example was 39.41±0.65% (p>0.05), the transmittance was 92.48±0.24% (p>0.05), and the contact angle was 34.52±0.28° (p>0.05).

[0088] Example 6

[0089] A method for preparing a drug-loaded contact lens comprises the following steps:

[0090] S1. Preparation of drug microemulsion:

[0091] The surfactant tetradecyl sulfopropyl betaine, the co-surfactant isobutyl alcohol and deionized water were mixed in volume proportions of 50 vol%, 15 vol% and 35 vol%, respectively, and nalidixic acid was added to the mixed solution, and ultrasonic mixing was performed to prepare a drug microemulsion with a concentration of 5 mg / mL.

[0092] S2. Preparation of contact lenses:

[0093] Silicon monomer KH-570, hydrophilic monomer HEMA, crosslinking agent diethylene glycol diacrylate and thermal initiator BPO were mixed in a mass ratio of 68.8wt%, 30wt%, 0.6wt% and 0.6wt%, respectively, and thermally polymerized in a constant temperature water bath at 90°C for 30 minutes, and then immersed in a 30vol% ethanol aqueous solution for 1 hour to remove unreacted monomers.

[0094] S3, soaking the contact lens in the levofloxacin microemulsion obtained in step S1 for 5 days to obtain a drug-loaded contact lens.

[0095] The equilibrium water content of the drug-loaded contact lens obtained in this example was 40.67±0.46% (p>0.05), the transmittance was 93.60±0.20% (p>0.05), and the contact angle was 32.53±0.34° (p>0.05).

[0096] The co-surfactant isobutyl alcohol in this embodiment can be replaced by one or more of ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-pentanol, and isopentanol; nalidixic acid can be replaced by one or more of levofloxacin, moxifloxacin, ofloxacin, ciprofloxacin, nalidixic acid, pipemidic acid, norfloxacin, enoxacin, lomefloxacin, pefloxacin, sparfloxacin, tobramycin, fluconazole, itraconazole, and ribavirin; the silicon monomer KH-570 can be replaced by IEM-terminated polydimethylsiloxane, HEMA-terminated polydimethylsiloxane, GMA-terminated polydimethylsiloxane, TRIS, The invention relates to an aqueous solution of at least one of KH-550, KH-570 and SIGMA; the hydrophilic monomer HEMA can be replaced by one or more of NVP, HPMA, DMA, HEMA, AA, AM, MMA, VMA, IEM, polyether polyol, SBMA and MPC; the crosslinking agent diethylene glycol diacrylate can be replaced by one or more of EGDMA, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, polyethylene glycol diacrylate or glycerol trimethacrylate and the thermal initiator BPO.

[0097] Example 7

[0098] This example aims to screen the stability of microemulsions with different volume ratios.

[0099] Table 1 Data of levofloxacin microemulsion system with different proportions

[0100]

[0101] The microemulsions with different volume ratios as shown in Table 1 were heated and cooled in cycles, and the phenomenon was observed by centrifugation. Phase separation occurred when Tween20: isopropanol: deionized water = 1:2:1.25 or 1:1:1.25. When Tween20: isopropanol: deionized water = 2:1:1.25, the most levofloxacin can be dissolved in the microemulsion, and the microemulsion system is the most thermodynamically stable, without phase separation. Therefore, Tween20: isopropanol: deionized water = 2:1:1.25 was selected as the optimal ratio of the drug-loaded microemulsion system, and it has thermodynamic stability. Then, the two groups of levofloxacin microemulsions with the best ratios were left at room temperature and 40°C for two months. After two months, there was no stratification, precipitation, flocculation and other phenomena in the levofloxacin microemulsions at different temperatures, indicating that the microemulsion system with the best ratio is stable.

Claims

1. A method for preparing a drug-loaded contact lens, characterized in that: The following steps are involved: Step 1, dissolving the drug in a mixed solution of a surfactant, a co-surfactant and deionized water to prepare a drug microemulsion; Step 2, uniformly mixing the silicon monomer, the hydrophilic monomer, the crosslinking agent and the initiator by ultrasonication, and obtaining the contact lens by compression molding, photopolymerization or thermal polymerization, and demolding; Step three, immersing the contact lens in the drug microemulsion to obtain the drug-loaded contact lens.

2. The method for preparing a drug-loaded contact lens according to claim 1, characterized in that: In the step 1, the drug is one or more of levofloxacin, moxifloxacin, ofloxacin, ciprofloxacin, nalidixic acid, pipemidic acid, norfloxacin, enoxacin, lomefloxacin, pefloxacin, sparfloxacin, tobramycin, fluconazole, itraconazole, and ribavirin; and the concentration of the drug microemulsion is 1 to 20 mg / mL.

3. The method for preparing a drug-loaded contact lens according to claim 1, characterized in that: In the step 1, the surfactant is polyoxyethylene fatty alcohol ether (Tween series) or tetradecyl sulfopropyl betaine, and the co-surfactant is one or more of ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol, and isopentanol.

4. The method for preparing a drug-loaded contact lens according to claim 1, characterized in that: In the step 1, the volume ratio of surfactant, co-surfactant and water is 2-6:1-3:2-5.

5. The method for preparing a drug-loaded contact lens according to claim 1, characterized in that: In the step 2, the silicon monomer is one or more of methacrylate-terminated polydimethylsiloxane, hydroxyethyl methacrylate-terminated polydimethylsiloxane, glycidyl methacrylate-terminated polydimethylsiloxane, methacryloxypropyl tris(trimethylsiloxy)silane, γ-aminopropyl triethoxysilane, γ-(methacryloxy)propyl trimethoxysilane, and propyl glyceryl methacrylate-based tris(trimethylsiloxy)methylsilane.

6. The method for preparing a drug-loaded contact lens according to claim 1, characterized in that: In the step 2, the hydrophilic monomer is one or more of N-vinyl pyrrolidone, hydroxypropyl methacrylate, N,N-dimethylacrylamide, β-hydroxyethyl methacrylate, acrylic acid, acrylamide, methyl methacrylate, N-vinyl-N-methylacetamide, isocyanoethyl methacrylate, polyether polyol, 2-methacryloyloxyethyl dimethyl 3-sulfonic acid propyl ammonium hydroxide, and 2-methacryloyloxyethyl phosphorylcholine.

7. The method for preparing a drug-loaded contact lens according to claim 1, characterized in that: In the step 2, the crosslinking agent is one or more of ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, polyethylene glycol diacrylate, and glycerol trimethacrylate.

8. The method for preparing a drug-loaded contact lens according to claim 1, characterized in that: In the step 2, the initiator is a photoinitiator or a thermal initiator, the photoinitiator is one or more of 2-hydroxyisobutyrophenone, 2-hydroxy-2-methyl-1-phenyl ketone, 1-hydroxy-cyclohexyl phenyl ketone, 4-phenylbenzophenone, and methyl o-benzoylbenzoate, and the thermal initiator is one or more of azobisisobutyronitrile, azobisisoheptanenitrile, benzoyl peroxide, di-tert-butyl peroxide, diisopropylbenzene peroxide, tert-butyl hydroperoxide, and 2,2-azobis(2-methylpropionamidine) dihydrochloride.

9. The method for preparing a drug-loaded contact lens according to claim 1, characterized in that: In the step 2, the mass ratio of the silicon monomer, the hydrophilic monomer, the crosslinking agent and the initiator is 10-88:10-40:0.5-1:0.5-1.

10. The drug-loaded contact lens obtained by the method for preparing a drug-loaded contact lens according to any one of claims 1 to 9, characterized in that: Its maximum drug loading capacity is 215.17~217.47μg / lens.

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