Contact lens with slow-release effect as well as preparation method and application thereof
By designing corneal contact lens-type contact lenses, coating inner and outer layers, and sealing protective layers, the problem of low drug precision in the treatment of dry eye syndrome is solved, achieving slow and continuous drug release, improving bioavailability and reducing side effects, and making it suitable for the treatment of a variety of ophthalmic diseases.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- GANSU TIANHOU OPTICAL TECHNOLOGY CO LTD
- Filing Date
- 2026-02-13
- Publication Date
- 2026-05-15
AI Technical Summary
Current treatments for dry eye suffer from low drug precision, poor bioavailability, and significant side effects. Existing ophthalmic devices lack precise drug delivery capabilities and have uncontrollable release rates.
A contact lens with a corneal contact lens structure is designed. The matrix is treated with plasma, coated with an inner drug loading layer and an outer rate control layer, and combined with an end-capping protective layer to achieve a sustained drug release effect.
It significantly improves the bioavailability of ocular drugs, with slow and continuous drug release over 5-10 days, eliminating the need for frequent dosing and reducing systemic diffusion. It combines physical adhesion and support with targeted drug delivery, making it suitable for the treatment of various dry eye syndromes and ophthalmic diseases.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of contact lens technology, and in particular to a contact lens with a sustained-release effect, its preparation method, and its application. Background Technology
[0002] Dry eye syndrome, also known as keratoconjunctivitis sicca, is caused by insufficient tear secretion, abnormal tear composition, or abnormal tear dynamics, leading to decreased tear film stability and causing discomfort such as dryness, foreign body sensation, burning sensation, and photophobia. In severe cases, it can lead to complications such as corneal and conjunctival diseases, damaging the function of ocular surface tissues. With the increasing aging population, the widespread use of electronic products, and environmental factors, the incidence of dry eye syndrome is rising year by year, especially among middle-aged and elderly people and those who use their eyes for long periods of time.
[0003] Current treatments for dry eye focus on relieving symptoms and restoring tear film function, primarily including artificial tear supplementation, topical application of anti-inflammatory drugs, and physical therapy. Topical drug administration is a commonly used clinical method, but existing methods have significant drawbacks: traditional eye drops are easily washed away by tears, resulting in extremely low bioavailability and requiring frequent administration to maintain effective blood drug concentrations. Furthermore, frequent administration can disrupt tear film stability, and some excipients and preservatives can exacerbate ocular surface irritation and damage. While ophthalmic gels and ointments can prolong drug retention time, they can cause side effects such as blurred vision, affecting patients' daytime activities. Oral medications, on the other hand, have significant systemic side effects and poor ocular targeting.
[0004] Existing products, such as drug-eluting stents, achieve precise localized sustained drug release through polymer coatings and have been successfully applied in the cardiovascular field. Their core advantage lies in combining the physical support function of the device with the targeted therapeutic function of the drug, enabling slow and continuous release of the drug at the lesion site, improving treatment efficacy and reducing systemic side effects. However, similar mature products have not yet emerged in the ophthalmology field. Most existing ophthalmic devices only possess physical functions (such as visual correction with corneal contact lenses and physical cleaning with eyelid cleaning instruments), lacking effective integration with precise drug delivery. Some attempts to load drug-eluting contact lenses suffer from problems such as uncontrollable drug release rates, weak adhesion between the coating and the lens substrate, and poor biocompatibility, making it difficult to meet clinical treatment needs.
[0005] Therefore, it is of great significance to develop a contact lens with sustained-release effect that combines good biocompatibility, controllable drug release, and targeting, as well as its preparation method and application. Summary of the Invention
[0006] The purpose of this invention is to provide a contact lens with a sustained-release effect, its preparation method, and its application, so as to solve the problems of low precision, poor drug bioavailability, and obvious side effects in existing treatments for dry eye syndrome.
[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: The present invention provides a contact lens with a sustained-release effect, the contact lens comprising the following structure: a contact lens substrate, a drug sustained-release coating, and an end-capping protective layer.
[0008] Preferably, the contact lens substrate is a corneal contact lens type structure; The contact lens substrate is made of fluorosilicone acrylate after plasma treatment.
[0009] Preferably, the drug sustained-release coating includes an inner drug loading layer and an outer rate control layer; In the inner drug loading layer, the carrier is a polylactic acid-glycolic acid copolymer, and the loading material includes an active ingredient and sodium hyaluronate. The active ingredient includes cyclosporine A, tacrolimus, or pilocarpine. The active ingredient accounts for 3-8 wt% of the inner drug loading layer, and sodium hyaluronate accounts for 1-3 wt% of the inner drug loading layer. The outer rate control layer comprises polymethyl methacrylate and polyethylene glycol, with a mass ratio of polymethyl methacrylate to polyethylene glycol of 90~95:5~10.
[0010] Preferably, the end-capping protective layer is hyaluronic acid; The molecular weight of the hyaluronic acid is 80,000 to 100,000 Da.
[0011] The present invention also provides a method for preparing a contact lens with a sustained-release effect, the method comprising the following steps: 1) The contact lens substrate is subjected to plasma treatment to obtain a pretreated substrate; 2) After coating the solution of the inner drug-loaded layer onto the pretreated substrate, it is dried once, and then the solution of the outer rate control layer is sprayed on and dried a second time to obtain a substrate with a drug sustained-release coating. 3) After immersing the substrate with the drug-releasing coating in the solution of the end-capping protective layer, remove it and cure it by ultraviolet light crosslinking to obtain a contact lens with a sustained-release effect.
[0012] Preferably, in step 1), the working gas in the plasma treatment is oxygen, the power is 80~120W, and the treatment time is 3~8min.
[0013] Preferably, in step 2), the mass fraction of the inner drug-loaded layer in the solution is 5-8 wt%, and the solvent is a dichloromethane-acetone mixed solvent with a volume ratio of dichloromethane to acetone of 2-3:1. The coating is a spin coating with a rotation speed of 300~500 rpm. The first drying is a vacuum drying with a vacuum degree of -0.08~-0.1 MPa, a drying time of 100~150 min, a drying temperature of 25~35℃, and a coating thickness of 60~80 μm after the first drying.
[0014] Preferably, in step 2), the outer rate control layer solution contains an outer rate control layer with a mass fraction of 3-5 wt% and anhydrous ethanol as the solvent. The spraying pressure is 0.2~0.3MPa, the secondary drying is hot air drying, the hot air drying temperature is 25~30℃, the hot air drying time is 60~100min, and the coating thickness after secondary drying is 20~35μm.
[0015] Preferably, in step 3), the solution of the end-capping protective layer has a mass fraction of 2-5 wt% and the solvent is PBS buffer. In ultraviolet crosslinking curing, the ultraviolet light wavelength is 254nm and the irradiation time is 20~40s; The thickness of the end-capping protective layer after UV cross-linking and curing is 5~10μm.
[0016] The present invention also provides an application of contact lenses with a sustained-release effect in relieving dry eye syndrome.
[0017] The beneficial effects of this invention are: The contact lens substrate of this invention adopts a corneal contact lens structure, which can precisely fit the ocular surface. The drug-releasing coating acts directly on the lesion site, preventing the drug from being rapidly washed away by tears and reducing drug diffusion into the systemic circulation, significantly improving the ocular drug concentration and bioavailability. Experiments using a rabbit dry eye model have verified that, compared to commercially available cyclosporine A eye drops, the ocular drug bioavailability of this invention is 3-5 times higher. Through a dual-layer gradient coating structure, the outer rate control layer can precisely regulate the drug release rate, achieving slow and continuous drug release over 5-10 days, eliminating the need for frequent administration and avoiding the irritation to the ocular surface caused by frequent drug administration.
[0018] The contact lenses obtained by this invention are non-toxic, non-irritating, and can be slowly degraded and metabolized, avoiding damage to the ocular surface from preservatives and excipients. The hyaluronic acid component of the end-capping protective layer can simultaneously relieve dryness symptoms and improve treatment comfort. Combining physical fit and support with targeted drug delivery, these lenses can be used not only to treat various types of dry eye, such as inflammatory and aqueous-deficient types, but also, by changing the loaded medication, to treat other ophthalmic diseases such as keratoconjunctivitis and ocular surface damage repair, demonstrating strong practicality.
[0019] The preparation method described in this invention has moderate equipment requirements, easy-to-control production process, and can achieve large-scale mass production, thus possessing good industrialization prospects. Detailed Implementation
[0020] The present invention provides a contact lens with a sustained-release effect, the contact lens comprising the following structure: a contact lens substrate, a drug sustained-release coating, and an end-capping protective layer.
[0021] In this invention, the contact lens substrate is preferably a corneal contact lens type structure; The contact lens substrate is made of fluorosilicone acrylate after plasma treatment.
[0022] In this invention, the diameter of the corneal contact lens structure is preferably 13.5~14.5mm, more preferably 13.8~14.2mm, and even more preferably 14mm, and the base curve is preferably 8~9.2mm, more preferably 8.2~9mm, and even more preferably 8.4~8.6mm; The fluorosilicone acrylate has high oxygen permeability, good wettability and mechanical stability, which can avoid corneal hypoxia and ocular surface irritation caused by long-term wear, and is suitable for the fragile ocular surface environment of patients with dry eye syndrome.
[0023] In this invention, the drug sustained-release coating includes an inner drug loading layer and an outer rate control layer; In the inner drug-loaded layer, the carrier is preferably a polylactic acid-glycolic acid copolymer, and the loading material preferably includes an active ingredient and sodium hyaluronate. The active ingredient preferably includes cyclosporine A, tacrolimus, or pilocarpine. The active ingredient preferably accounts for 3-8 wt% of the inner drug-loaded layer, more preferably 4-7 wt%, and even more preferably 5-6 wt%. Sodium hyaluronate preferably accounts for 1-3 wt% of the inner drug-loaded layer, more preferably 1.5-2.5 wt%, and even more preferably 2-2.2 wt%. The outer rate control layer further comprises polymethyl methacrylate and polyethylene glycol, with the mass ratio of polymethyl methacrylate to polyethylene glycol preferably being 90~95:5~10, more preferably 91~94:6~9, and even more preferably 92~93:7~8.
[0024] In this invention, the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is preferably 50:50. This ratio allows for a more stable degradation rate in the weakly acidic environment of the ocular surface, avoids sudden drug release, and provides a suitable degradation rate and drug loading capacity. The addition of sodium hyaluronate improves the wettability and biocompatibility of the coating, and can also form hydrogen bonds with the drug to stabilize the drug structure and prevent premature drug leakage.
[0025] In this invention, the polyethylene glycol in the outer rate control layer is preferably PEG-400. As a plasticizer, polyethylene glycol can adjust the porosity and dissolution rate of the coating to achieve slow drug release.
[0026] In this invention, the drug sustained-release coating has a dual-layer gradient structure, including an inner drug-loaded layer and an outer rate-control layer, both made of biocompatible polymer materials. It can slowly degrade in the weakly acidic microenvironment of the ocular surface, with a complete degradation cycle of 7-12 days, which is precisely matched with the drug release cycle. The degradation products are lactic acid, glycolic acid and polyethylene glycol fragments, which are non-cytotoxic and can be metabolized by ocular surface tissues or excreted with tears.
[0027] In this invention, the end-capping protective layer is preferably hyaluronic acid; The molecular weight of the hyaluronic acid is preferably 80,000 to 100,000 Da, more preferably 85,000 to 95,000 Da, and even more preferably 88,000 to 90,000 Da.
[0028] In this invention, the end-capping protective layer serves three purposes: first, it forms a physical barrier during the initial storage and wearing stages to prevent drug leakage during non-treatment phases; second, it rapidly integrates with ocular surface tears to form a lubricating film, relieving dryness and discomfort in patients with dry eye syndrome; and third, it has excellent biocompatibility, can be degraded into glucuronic acid by ocular surface tear lysozyme, and is metabolized and absorbed by ocular surface tissues without residual irritation.
[0029] The present invention also provides a method for preparing a contact lens with a sustained-release effect, the method comprising the following steps: 1) The contact lens substrate is subjected to plasma treatment to obtain a pretreated substrate; 2) After coating the solution of the inner drug-loaded layer onto the pretreated substrate, it is dried once, and then the solution of the outer rate control layer is sprayed on and dried a second time to obtain a substrate with a drug sustained-release coating. 3) After immersing the substrate with the drug-releasing coating in the solution of the end-capping protective layer, remove it and cure it by ultraviolet light crosslinking to obtain a contact lens with a sustained-release effect.
[0030] In this invention, in step 1), the working gas in the plasma treatment is preferably oxygen, the power is preferably 80~120W, more preferably 90~110W, more preferably 100~105W, and the treatment time is preferably 3~8min, more preferably 4~7min, and more preferably 5~6min.
[0031] In this invention, in step 1), the contact lens substrate is preferably cleaned with anhydrous ethanol, cleaned with water, and dried sequentially before plasma treatment; The anhydrous ethanol cleaning is preferably ultrasonic cleaning, with an ultrasonic cleaning frequency of 35~45kHz, more preferably 36~42kHz, more preferably 38~40kHz, and an ultrasonic cleaning time of 10~18min, more preferably 12~17min, and more preferably 14~15min. The water rinsing is preferably performed 3 to 5 times, and more preferably 4 times; The drying process is preferably carried out by nitrogen blowing.
[0032] In this invention, the surface of the contact lens substrate is treated with plasma to form a hydroxylated surface, which enhances the bonding strength with subsequent coatings and prevents the coating from peeling off.
[0033] In this invention, in step 2), the mass fraction of the inner drug-loaded layer in the solution is preferably 5-8 wt%, more preferably 5.5-7 wt%, and even more preferably 6-6.5 wt%. The solvent is preferably a dichloromethane-acetone mixed solvent, and the volume ratio of dichloromethane to acetone is preferably 2-3:1, more preferably 2.2-2.8:1, and even more preferably 2.4-2.6:1. The coating is preferably spin coating, with a rotation speed preferably 300-500 rpm, more preferably 350-450 rpm, and even more preferably 400-420 rpm. The primary drying is preferably vacuum drying, with a vacuum degree preferably -0.08--0.1 MPa, more preferably -0.085--0.095 MPa, and even more preferably -0.09 MPa. The primary drying time is preferably 100-150 min, more preferably 110-140 min, and even more preferably 120-130 min. The primary drying temperature is preferably 25-35℃, more preferably 27-32℃, and even more preferably 28-30℃. The coating thickness after primary drying is preferably 60-80 μm, more preferably 65-75 μm, and even more preferably 70-72 μm.
[0034] In this invention, in step 2), the mass fraction of the outer rate control layer in the solution of the outer rate control layer is preferably 3-5 wt%, more preferably 3.5-4.5 wt%, and even more preferably 3.8-4 wt%, and the solvent is preferably anhydrous ethanol; The spraying pressure is preferably 0.2~0.3MPa, more preferably 0.22~0.28MPa, and even more preferably 0.24~0.26MPa. The secondary drying is preferably hot air drying, the hot air drying temperature is preferably 25~30℃, more preferably 26~29℃, and even more preferably 27~28℃. The hot air drying time is preferably 60~100min, more preferably 70~95min, and even more preferably 80~90min. The coating thickness after secondary drying is preferably 20~35μm, more preferably 24~32μm, and even more preferably 26~30μm.
[0035] In this invention, in step 3), the mass fraction of the end-capping protective layer in the solution is preferably 2-5 wt%, more preferably 2.5-4.5 wt%, and even more preferably 3-4 wt%, and the solvent is preferably PBS buffer. In ultraviolet light crosslinking curing, the ultraviolet light wavelength is preferably 254 nm, and the irradiation time is preferably 20~40 s, more preferably 25~35 s, and even more preferably 30~32 s. The thickness of the end-capping protective layer after UV crosslinking and curing is preferably 5~10μm, more preferably 6~9μm, and even more preferably 7~8μm.
[0036] In this invention, the pH value of the PBS buffer is preferably 7.2 to 7.5, and more preferably 7.3 to 7.4.
[0037] In this invention, after the ultraviolet light crosslinking and curing, the product is preferably sterilized, and the sterilization is preferably gamma-ray sterilization, with the gamma-ray sterilization dose preferably being 25 kGy.
[0038] The present invention also provides an application of contact lenses with a sustained-release effect in relieving dry eye syndrome.
[0039] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.
[0040] Example 1
[0041] Structural parameters: Contact lens matrix: Corneal contact lens type structure, with a diameter of 14mm and a base curve of 8.5mm, made of fluorosilicone acrylate through plasma treatment; Drug-release coating: Inner drug-loaded layer: The carrier is polylactic acid-glycolic acid copolymer (lactic acid to glycolic acid molar ratio 50:50), and the loading materials are cyclosporine A (accounting for 5 wt% of the inner drug-loaded layer) and sodium hyaluronate (accounting for 2 wt% of the inner drug-loaded layer). Outer rate control layer: polymethyl methacrylate to PEG-400 mass ratio 92:8; End capping protective layer: hyaluronic acid, molecular weight 89000 Da; Preparation method: The contact lens substrate was placed in anhydrous ethanol and ultrasonically cleaned at a frequency of 40kHz for 15 minutes, then rinsed with water 4 times, and finally dried with nitrogen. Then, it was plasma treated with oxygen as the working gas at a power of 100W for 5 minutes to obtain the pretreated substrate. The inner drug-loaded layer was mixed with a dichloromethane-acetone mixed solvent (dichloromethane to acetone volume ratio of 2.5:1) to obtain a solution of the inner drug-loaded layer with a mass fraction of 6 wt%. The outer rate control layer was mixed with anhydrous ethanol to obtain a solution of the outer rate control layer with a mass fraction of 3.8 wt%. The end-capping protective layer was mixed with a PBS buffer solution with a pH of 7.4 to obtain a solution of the end-capping protective layer with a mass fraction of 3 wt%. The solution of the inner drug-loaded layer was coated onto the pretreated substrate by spin coating at a speed of 400 rpm, and then vacuum dried at 30°C for 120 min under a vacuum of -0.09 MPa to obtain a substrate with a drug-loaded layer of 70 μm. The solution of the outer rate control layer was sprayed onto the substrate of the drug-loaded layer at a spraying pressure of 0.25 MPa, and then dried with hot air at 27°C for 85 min to obtain a substrate with a 28 μm rate control layer. The substrate with the rate control layer is immersed in the solution of the end capping protective layer and then removed. It is then cross-linked and cured by irradiation with 254nm ultraviolet light for 30s to obtain a matrix with a 7.5μm end capping protective layer. After sterilization with 25kGy γ-rays, a contact lens with a sustained-release effect is obtained.
[0042] Example 2
[0043] Structural parameters: Contact lens matrix: Corneal contact lens type structure, with a diameter of 13.8mm and a base curve of 8.4mm, made of fluorosilicone acrylate through plasma treatment; Drug-release coating: Inner drug loading layer: The carrier is polylactic acid-glycolic acid copolymer (lactic acid to glycolic acid molar ratio 50:50), and the loading materials are tacrolimus (4 wt% of the inner drug loading layer) and sodium hyaluronate (1.5 wt% of the inner drug loading layer). Outer rate control layer: polymethyl methacrylate to PEG-400 mass ratio 93:7; End capping protective layer: hyaluronic acid, molecular weight 85000 Da; Preparation method: The contact lens substrate was placed in anhydrous ethanol and ultrasonically cleaned at a frequency of 38kHz for 15 minutes, then rinsed with water 4 times, and finally dried with nitrogen. Then, it was plasma treated with oxygen as the working gas at a power of 90W for 6 minutes to obtain the pretreated substrate. The inner drug-loaded layer was mixed with a dichloromethane-acetone mixed solvent (dichloromethane to acetone volume ratio of 2.5:1) to obtain a solution of the inner drug-loaded layer with a mass fraction of 5.5 wt%. The outer rate control layer was mixed with anhydrous ethanol to obtain a solution of the outer rate control layer with a mass fraction of 4 wt%. The end-capping protective layer was mixed with a PBS buffer solution with a pH of 7.4 to obtain a solution of the end-capping protective layer with a mass fraction of 3.5 wt%. The solution of the inner drug-loaded layer was coated onto the pretreated substrate by spin coating at a speed of 380 rpm, and then vacuum dried at 30°C for 120 min under a vacuum of -0.085 MPa to obtain a substrate with a drug-loaded layer of 68 μm. The solution of the outer rate control layer was sprayed onto the substrate of the drug-loaded layer at a spraying pressure of 0.25 MPa, and then dried with hot air at 28°C for 80 min to obtain a substrate with a 26 μm rate control layer. The substrate with the rate control layer is immersed in the solution of the end capping protective layer and then removed. It is then crosslinked and cured by irradiation with 254nm ultraviolet light for 32s to obtain a matrix with a 7μm end capping protective layer. After sterilization with 25kGy γ rays, a contact lens with a sustained-release effect is obtained.
[0044] Example 3
[0045] Structural parameters: Contact lens matrix: Corneal contact lens type structure, with a diameter of 14.2mm and a base curve of 8.6mm, made of fluorosilicone acrylate through plasma treatment; Drug-release coating: Inner drug loading layer: The carrier is polylactic acid-glycolic acid copolymer (lactic acid to glycolic acid molar ratio 50:50), and the loading materials are tacrolimus (6 wt% of the inner drug loading layer) and sodium hyaluronate (2.2 wt% of the inner drug loading layer). Outer rate control layer: polymethyl methacrylate to PEG-400 mass ratio 91:9; End capping protective layer: hyaluronic acid, molecular weight 95000 Da; Preparation method: The contact lens substrate was placed in anhydrous ethanol and ultrasonically cleaned at a frequency of 40kHz for 15 minutes, then rinsed with water 4 times, and finally dried with nitrogen. Then, it was plasma treated with oxygen as the working gas at a power of 110W for 4 minutes to obtain the pretreated substrate. The inner drug-loaded layer was mixed with a dichloromethane-acetone mixed solvent (dichloromethane to acetone volume ratio of 2.6:1) to obtain a solution of the inner drug-loaded layer with a mass fraction of 6.5 wt%. The outer rate control layer was mixed with anhydrous ethanol to obtain a solution of the outer rate control layer with a mass fraction of 3.5 wt%. The end-capping protective layer was mixed with a PBS buffer solution with a pH of 7.4 to obtain a solution of the end-capping protective layer with a mass fraction of 3.5 wt%. The solution of the inner drug-loaded layer was coated onto the pretreated substrate by spin coating at a speed of 420 rpm, and then vacuum dried at 30 °C for 120 min under a vacuum of -0.095 MPa to obtain a substrate with a drug-loaded layer of 72 μm. The solution of the outer rate control layer was sprayed onto the substrate of the drug-loaded layer at a spraying pressure of 0.25 MPa, and then dried with hot air at 28°C for 80 min to obtain a substrate with a 30 μm rate control layer. After immersing the substrate with the rate control layer into the solution of the end-capping protective layer, it is removed and cross-linked and cured by irradiation with 254nm ultraviolet light for 32s to obtain a matrix with an 8μm end-capping protective layer. Then, it is sterilized by 25kGy γ-rays to obtain a contact lens with a sustained-release effect.
[0046] Comparative Example 1
[0047] Compared to Example 1, the outer rate control layer is removed, while the other steps are the same as in Example 1.
[0048] Comparative Example 2
[0049] Compared with Example 1, the end cap protective layer is removed, while the other steps are the same as in Example 1.
[0050] Comparative Example 3
[0051] Commercially available eye drops containing 0.05% cyclosporine A were selected as the baseline control group for bioavailability testing. The administration method was routine ocular instillation, 1 drop twice daily.
[0052] The contact lenses obtained in Examples 1-3, the contact lenses obtained in Comparative Examples 1-2, and the eye drops in Comparative Example 3 were tested as follows: Detection objects and models: Forty-eight healthy New Zealand white rabbits, weighing 2-2.5 kg, with half males and half females, were randomly divided into six groups (Example 1-3, Comparative Examples 1-2, and Comparative Example 3), with eight rabbits in each group. A rabbit dry eye model was constructed by applying 0.1% benzalkonium chloride solution to the eyes (one drop three times a day for seven consecutive days). After successful modeling, interventions were implemented in each experimental group.
[0053] Drug sustained-release period and release rate: Contact lenses of each experimental group were immersed in simulated tear fluid (pH 7.4, constant temperature oscillation at 37℃, rotation speed 50 rpm). Samples were taken at 1d, 2d, 3d, 5d, 7d, 10d, and 12d. The drug concentration in the release fluid was determined by high performance liquid chromatography. The time when the cumulative drug release rate reached 80% (sustained-release period) was recorded, and the average daily release rate was calculated. The test results are shown in Table 1.
[0054] Table 1 Results of drug sustained-release period and release rate detection
[0055] Coating adhesion stability: The integrity of the surface coating of the contact lens was observed daily after wearing (observed under an optical microscope), and the time when the coating peeled off or cracked was recorded. The test results are shown in Table 2.
[0056] Table 2. Coating adhesion stability test results
[0057] Ocular surface irritation and safety: After the intervention, rabbit corneal tissue was taken and stained with hematoxylin and eosin (HE) to observe histopathological changes. The MTT assay was used to detect the toxicity of coating degradation products to corneal epithelial cells. Cell viability ≥90% was considered non-toxic. The test results are shown in Table 3.
[0058] Table 3 Results of ocular surface irritation and safety tests
[0059] Dry eye relief effect: Before intervention and at 3, 7 and 10 days after intervention, tear secretion volume (mm / 5min) was measured by tear secretion test, and tear film stability was measured by tear film breakup time (s). The test results are shown in Table 4.
[0060] Table 4 Results of Dry Eye Syndrome Relief Test
[0061] As shown in Tables 1-4, the contact lenses prepared in Examples 1-3 possess both excellent drug sustained-release performance and safety. The sustained-release period is 7.5-9 days, enabling slow and continuous drug release. Furthermore, the coating is stable and non-irritating to the ocular surface. The relief effect on dry eye syndrome is significantly better than that of the products in Comparative Examples 1-2 and the commercial eye drops shown in Comparative Example 3. Among them, Comparative Example 1 experienced drug burst release due to the lack of an outer rate control layer, and Comparative Example 2 suffered from initial drug leakage and increased ocular surface irritation due to the lack of a capping protective layer. Both significantly reduced the sustained-release effect and user experience, confirming the key roles of the double-layer gradient coating structure and the capping protective layer in achieving precise sustained release, ensuring drug retention, and improving safety.
[0062] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A contact lens with a sustained-release effect, characterized in that, The contact lens comprises the following structure: a contact lens matrix, a drug-releasing coating, and an end-capping protective layer.
2. The contact lens with sustained-release effect according to claim 1, characterized in that, The contact lens substrate has a corneal contact lens type structure; The contact lens substrate is made of fluorosilicone acrylate after plasma treatment.
3. The contact lens with sustained-release effect according to claim 1, characterized in that, The drug sustained-release coating includes an inner drug loading layer and an outer rate control layer; In the inner drug loading layer, the carrier is a polylactic acid-glycolic acid copolymer, and the loading material includes an active ingredient and sodium hyaluronate. The active ingredient includes cyclosporine A, tacrolimus, or pilocarpine. The active ingredient accounts for 3-8 wt% of the inner drug loading layer, and sodium hyaluronate accounts for 1-3 wt% of the inner drug loading layer. The outer rate control layer comprises polymethyl methacrylate and polyethylene glycol, with a mass ratio of polymethyl methacrylate to polyethylene glycol of 90~95:5~10.
4. The contact lens with sustained-release effect according to claim 1, characterized in that, The end-capping protective layer is hyaluronic acid; The molecular weight of the hyaluronic acid is 80,000 to 100,000 Da.
5. A method for preparing a contact lens with a sustained-release effect according to any one of claims 1 to 4, characterized in that, The preparation method includes the following steps: 1) The contact lens substrate is subjected to plasma treatment to obtain a pretreated substrate; 2) After coating the solution of the inner drug-loaded layer onto the pretreated substrate, it is dried once, and then the solution of the outer rate control layer is sprayed on and dried a second time to obtain a substrate with a drug sustained-release coating. 3) After immersing the substrate with the drug sustained-release coating in the solution of the end-capping protective layer, remove it and cure it by ultraviolet light crosslinking to obtain a contact lens with sustained-release effect.
6. The method for preparing a contact lens with a sustained-release effect according to claim 5, characterized in that, In step 1), the working gas in the plasma treatment is oxygen, the power is 80~120W, and the treatment time is 3~8min.
7. The method for preparing a contact lens with a sustained-release effect according to claim 5, characterized in that, In step 2), the mass fraction of the inner drug-loaded layer in the solution is 5-8 wt%, and the solvent is a dichloromethane-acetone mixed solvent with a volume ratio of dichloromethane to acetone of 2-3:
1. The coating is a spin coating with a rotation speed of 300~500 rpm. The first drying is a vacuum drying with a vacuum degree of -0.08~-0.1 MPa, a drying time of 100~150 min, a drying temperature of 25~35℃, and a coating thickness of 60~80 μm after the first drying.
8. The method for preparing a contact lens with a sustained-release effect according to claim 5, characterized in that, In step 2), the outer rate control layer solution contains an outer rate control layer with a mass fraction of 3-5 wt% and anhydrous ethanol as the solvent. The spraying pressure is 0.2~0.3MPa, the secondary drying is hot air drying, the hot air drying temperature is 25~30℃, the hot air drying time is 60~100min, and the coating thickness after secondary drying is 20~35μm.
9. The method for preparing a contact lens with a sustained-release effect according to claim 5, characterized in that, In step 3), the mass fraction of the end-capping protective layer in the solution is 2-5 wt%, and the solvent is PBS buffer. In ultraviolet crosslinking curing, the ultraviolet light wavelength is 254nm and the irradiation time is 20~40s; The thickness of the end-capping protective layer after UV cross-linking and curing is 5~10μm.
10. The application of a contact lens with a sustained-release effect as described in any one of claims 1 to 4 in the field of relieving dry eye syndrome.