Contact lens impregnated with pharmaceutical agent for treating allergic conjunctivitis and manufacturing method thereof

Abstract

The present invention provides: a method for impregnating a contact lens with a drug; and a drug-impregnated contact lens manufactured by the method. The present invention is for easily treating ophthalmic diseases using the drug-impregnated contact lens, and has the specific objective of providing a medical device for simple treatment of allergic conjunctivitis.

Description

Contact lens containing a pharmaceutical preparation for treating allergic conjunctivitis and method for manufacturing the same

[0001] This application claims the benefit of Korean Patent Application No. 10-2024-0117414, filed with the Korean Intellectual Property Office on August 30, 2024, and the benefit of Korean Patent Application No. 10-2025-0080937, filed with the Korean Intellectual Property Office on June 19, 2025, the entire contents of which are incorporated herein by reference.

[0002] The present invention is an invention that provides a method for loading a drug into a contact lens and a drug-loaded contact lens manufactured by the method, and is an invention that provides a medical device for the simple treatment of ophthalmic diseases.

[0003]

[0004] Allergic conjunctivitis, an allergic reaction to the conjunctiva, is a common eye condition that many people have experienced. However, the symptoms of allergic conjunctivitis cause discomfort and pain in many people. Specifically, symptoms of allergic conjunctivitis include itching, redness, eyelid swelling, a foreign body sensation, and excessive discharge and mucus production. In severe cases, the condition can persist, leading to vision loss or impairment, necessitating prompt treatment.

[0005] The above allergic conjunctivitis can be divided into immediate hypersensitivity reactions such as Hay fever conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis, and delayed hypersensitivity reactions such as conjunctivitis caused by phlyctenulosis and contact dermatitis-induced conjuctivitis. These can be classified according to the type and form of secretion.

[0006] The causes of allergic conjunctivitis are diverse, including environmental allergens such as pollen, yellow dust, fine dust, mites, animal hair, and mold; contact allergens such as contact lens solution, cosmetics, or preservatives in artificial tears; and genetic factors due to the inheritance of allergic constitution.

[0007] In order to treat the allergy, it is well known that the current method of avoiding the cause of the allergy (allergen) itself and the method of applying antihistamines, mast cell stabilizers, steroids, and oral antihistamine eye drops are well known, but simply avoiding the allergen is actually a very difficult treatment method for modern people, and the method of administering eye drops is quite cumbersome because they have to be administered at a set time, and even if eye drops are used, there are problems such as the loss of the drug being large compared to the actual absorbed amount, reducing the effectiveness of the treatment.

[0008] In particular, as the proportion of the population wearing contact lenses has recently increased, administering eye drops requires a cumbersome process, such as removing contact lenses and administering eye drops, and there is a risk of exposure to secondary infections.

[0009] The above contact lenses are generally divided into soft contact lenses and hard contact lenses, and both are devices that are directly attached to the eye to correct vision. As various types of contact lenses are released, including not only for vision correction but also for cosmetic purposes and lenses with special functions, the proportion of the population using contact lenses is gradually increasing.

[0010] Accordingly, in order to improve the inconvenience, discomfort, and treatment difficulties of users of contact lenses in the treatment of allergic conjunctivitis as mentioned above, the present invention provides a method for gradually inducing treatment of allergic conjunctivitis through penetration of the drug by impregnating the drug in a contact lens when the contact lens is worn, and a contact lens manufactured thereby.

[0011]

[0012] The present invention provides a method for manufacturing a drug-loaded contact lens and a contact lens manufactured thereby for the treatment and improvement of conjunctivitis in a patient with allergic conjunctivitis or a contact lens wearer with allergic conjunctivitis.

[0013] In addition, the invention aims to provide a method for helping treat patients with diseases by inducing continuous drug release.

[0014] Currently, drug delivery systems for ophthalmic diseases are primarily provided in the form of eye drops. However, this method can lead to irregular drug administration and discomfort. Existing eye drops reduce patient compliance and limit the duration and effectiveness of the drug. Therefore, new drug delivery methods are urgently needed.

[0015]

[0016] In order to solve the above-mentioned problem, the present invention is an invention that provides a method for loading a drug into a contact lens and a contact lens manufactured by the method.

[0017] As one specific example of the invention, the drug may include one or more drugs selected from the group consisting of antihistamines, mast cell stabilizers, steroid eye drops, non-steroidal anti-inflammatory drugs, and oral antihistamines.

[0018] As one specific example of the invention, the contact lens may be one or more types of contact lenses selected from the group consisting of a soft hydrogel, a silicone hydrogel, a PMMA (polymethyl methacrylate, rigid lens), a RGP (rigid gas permeable lens), a hybrid lens (RGP in the center and soft material at the edge), and a scleral lens (a large RGP lens that completely covers the cornea).

[0019]

[0020] The present invention aims to provide a simpler and more effective treatment method for patients with ocular allergies, potentially contributing to increased patient compliance and maintaining ocular health in the long term. Furthermore, compared to existing eye drops, this contact lens method improves user convenience, enables uniform drug release, and maximizes the effectiveness of drug treatment. Furthermore, it effectively delivers the drug without compromising the basic functions of the contact lens.

[0021]

[0022] Figure 1 is a graph showing changes in physical properties when cetirizine is incorporated into a contact lens, and confirms changes in diameter and moisture content, respectively.

[0023] Figure 2 shows the results of confirming the loading amount of cetirizine in contact lenses.

[0024] Figure 3 is a graph confirming the release characteristics of cetirizine from a contact lens.

[0025] Figure 4 shows the results of confirming the refractive power and visible light transmittance when cetirizine is contained in a contact lens.

[0026] Figure 5 shows the results of confirming the interaction with cetirizine using a protein similar to a protein present in tears.

[0027] Figure 6 shows the results of confirming the standard curve of cetirizine.

[0028] Figures 7 and 8 are graphs showing the amount of cetirizine released from each type of contact lens.

[0029] Figures 9 and 10 show the results of comparing the adsorption and release amounts of cetirizine of different types of contact lenses.

[0030] Figure 11 is a graph showing the water content after cetirizine is adsorbed on contact lenses of different types.

[0031] Figure 12 is a graph showing the change in diameter after cetirizine is adsorbed on contact lenses of different types.

[0032] Figure 13 shows the results of confirming the standard curves of cetirizine and epinastine, respectively.

[0033] Figure 14 shows the results showing the contact lens adsorption rates of cetirizine and epinastine.

[0034] Figure 15 shows the results of drug release from contact lenses of cetirizine and epinastine.

[0035] Figure 16 shows the results of confirming drug adsorption and release according to the concentration of cetirizine and epinastine.

[0036] Figure 17 shows the results of confirming the change in water content and diameter after drug adsorption according to the concentration of cetirizine and epinastine.

[0037]

[0038] The present invention provides a contact lens containing a pharmaceutical agent for treating ophthalmic diseases.

[0039] As a specific example of the invention, the ophthalmic disease is allergic conjunctivitis, and specifically, it may be at least one ophthalmic disease selected from the group consisting of immediate hypersensitivity reactions including Hay fever conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis; delayed hypersensitivity reactions including conjunctivitis due to phlyctenulosis and contact dermatitis induced conjuctivitis, but is not limited thereto.

[0040] As a specific example of the invention, the pharmaceutical preparation may be at least one pharmaceutical preparation selected from the group consisting of an antihistamine, a mast cell stabilizer, a steroid, and an oral antihistamine, specifically, it may be an antihistamine and a mast cell stabilizer, and more specifically, it may be an antihistamine.

[0041] As a specific example of the invention, the antihistamine may include one or more pharmaceutical preparations selected from the group consisting of Cetirizine, Epinastine, Olopatadine, Ketotifen, Azelastine, Levocabastine, Emedastine, and Bepotastine, specifically Cetirizine and Epinastine, and more specifically Cetirizine.

[0042] As a specific example of the invention, the contact lens may include at least one contact lens selected from the group consisting of a non-ionic-low water content hydrogel contact lens, a non-ionic-high water content hydrogel contact lens, an ionic-high water content hydrogel contact lens, and a silicone hydrogel contact lens, and specifically, may be at least one type of contact lens selected from the group consisting of a hydrogel (soft hydrogel), a silicone hydrogel, PMMA (polymethyl methacrylate, rigid lens), an RGP (rigid gas permeable lens), a hybrid lens (RGP in the center, soft material at the edge), and a scleral lens (a large RGP lens that completely covers the cornea), and more specifically, may be a hydrogel-based contact lens.

[0043] As a specific example of the invention, the type of the contact lens may be at least one contact lens selected from the group consisting of Omafilcon A, Somofilcon A, Stenfilcon A, Lotrafilcon A, Delefilcon A, Nesofilcon A, Etafilcon A, Narafilcon A, Senofilcon A, Senofilcon C and Hilafilcon B, specifically Hilafilcon B, Etafilcon A, Nesofilcon A, Somofilcon, Narafilcon A, Senofilcon A and Omafilcon A, and more specifically Etafilcon A and Narafilcon.

[0044] As one specific example of the invention, the contact lens may be a sustained-release contact lens that slowly releases a pharmaceutical agent.

[0045] As a specific example of the invention, the contact lens contains a pharmaceutical preparation, but has little change in physical properties, and the physical properties are curvature, moisture content, and diameter.

[0046]

[0047] The present invention may provide a method for manufacturing a contact lens containing a pharmaceutical preparation, comprising the following steps.

[0048] (1) A step of treating a pharmaceutical preparation with a solution for contact lens application;

[0049] (2) A step of immersing a contact lens in a solution treated with the pharmaceutical preparation produced in (1) above;

[0050] (3) A step of separating and washing the contact lens containing the pharmaceutical preparation in (2) above.

[0051] As a specific example of the invention, the pharmaceutical preparation of step (1) may be at least one pharmaceutical preparation selected from the group consisting of an antihistamine, a mast cell stabilizer, a steroid, and an oral antihistamine, specifically, it may be an antihistamine and a mast cell stabilizer, and more specifically, it may be an antihistamine.

[0052] As a specific example of the invention, the antihistamine may include one or more pharmaceutical preparations selected from the group consisting of Cetirizine, Epinastine, Olopatadine, Ketotifen, Azelastine, Levocabastine, Emedastine, and Bepotastine, specifically Cetirizine and Epinastine, and more specifically Cetirizine.

[0053] As a specific example of the invention, the pharmaceutical preparation in step (1) may be included at a concentration of 1 to 5 mM, specifically, at a concentration of 2 to 4 mM, and more specifically, at a concentration of 3 mM.

[0054] As a specific example of the invention, the contact lens solution in step (1) may be composed of one or more contact lens solution selected from the group consisting of phosphate-buffered saline (PBS), multi-purpose solution (MPS), saline solution, Ringer's solution, Hank's balanced salt solution (HBSS), multipurpose disinfecting solution (MPDS), and rewet drops, and specifically, may be PBS and MPS solutions.

[0055] As a specific example of the invention, the contact lens containing solution in step (1) may be 0.5 to 2.0 mL, specifically 0.7 to 1.5 mL, and more specifically 1.0 mL.

[0056] As a specific example of the invention, the MPS may include a polyhexamethylene biguanide hydrochloride (PHMB-HCl) solution and an etidronic acid tetrasodium (HEDP 4Na) solution.

[0057] As a specific example of the invention, the hydrochloric acid polyhexamethylene biguanide solution may be included in the MPS at a concentration of 10 to 30%, specifically, may be included in the MPS at a concentration of 15 to 25%, and more specifically, may be included in the MPS at a concentration of 20%.

[0058] As a specific example of the invention, the etidronate tetrasodium solution may be included in the MPS at a concentration of 20 to 40%, specifically at a concentration of 25 to 35%, and more specifically at a concentration of 30%.

[0059] As a specific example of the invention, the time for immersing the contact lens in the solution in step (2) may be 1 to 3 hours, specifically 1.5 to 2.5 hours, and more specifically 2 hours.

[0060]

[0061] As one specific example of the invention, the present invention provides a solution composition for containing a pharmaceutical agent for treating allergic conjunctivitis in a contact lens; or a solution for containing a contact lens. Specifically, the invention provides a solution for containing a contact lens for treating allergic conjunctivitis.

[0062]

[0063] As a specific example of the invention, the solution composition for containing the pharmaceutical agent for treating allergic conjunctivitis in a contact lens is at least one solution selected from the group consisting of phosphate-buffered saline (PBS), multi-purpose solution (MPS), saline solution, Ringer's solution, Hank's balanced salt solution (HBSS), multipurpose disinfecting solution (MPDS) and rewet drops, and specifically, at least one solution selected from the group consisting of phosphate-buffered saline (PBS), multi-purpose solution (MPS) and saline solution, and more specifically, phosphate-buffered saline (PBS) and It may be a multi-purpose solution (MPS).

[0064] As a specific example of the invention, a solution composition for containing a pharmaceutical agent for treating allergic conjunctivitis in a contact lens may be composed of 10 to 30 wt% of a polyhexamethylene biguanide hydrochloride (PHMB-HCl) solution, 10 to 30 wt% of an etidronate tetrasodium (HEDP 4Na) solution, and 40 to 80 wt% of PBS (phosphate-buffered saline). Specifically, as a specific example of the invention, the polyhexamethylene biguanide hydrochloride solution may be included in MPS at a concentration of 10 to 30%, specifically, at a concentration of 15 to 25%, and more specifically, at a concentration of 20%. Additionally, the etidronate tetrasodium solution may be included in a concentration of 20 to 40%, specifically in a concentration of 25 to 35%, and more specifically in a concentration of 30%.

[0065] As a specific example of the invention, the pharmaceutical agent of the solution composition for containing the pharmaceutical agent for treating allergic conjunctivitis in a contact lens may further include one or more pharmaceutical agents selected from the group consisting of antihistamines, mast cell stabilizers, steroid eye drops, non-steroidal anti-inflammatory agents, and oral antihistamines, and specifically, the pharmaceutical agent may be one or more pharmaceutical agents selected from the group consisting of Cetirizine, Epinastine, Olopatadine, Ketotifen, Azelastine, Levocabastine, Emedastine, and Bepotastine, and more specifically, Cetirizine and / or Epinastine.

[0066] As a specific example of the invention, the pharmaceutical formulation may be included in the contact lens solution at a concentration of 1 to 5 mM, specifically at a concentration of 2 to 4 mM, and more specifically at a concentration of 3 mM, but is not limited thereto.

[0067] As one specific example of the invention, a contact lens solution is configured to function as a drug delivery system, is applicable to contact lenses containing pharmaceutical formulations, and is configured with a composition capable of simultaneously performing the functions of cleaning, preserving, and disinfecting. The solution may include preservatives, buffers, chelating agents, moisturizers, surfactants, and isotonic agents, which are commonly used ingredients for contact lens care.

[0068] Specifically, it may include preservatives (e.g., polyaminopropyl biguanide, polyquaternium-1, mirodexamine (Aldox)), chelating agents (e.g., sodium edetate (EDTA)), buffers (e.g., boric acid, sodium boroate, sodium chloride, sodium citrate), isotonic agents (e.g., sodium chloride, potassium chloride), humectants (e.g., propylene glycol, sorbitol, tetrasodium isetrate), lubricants, and surfactants (e.g., Tetronic, tetramethylene oxide derivatives).

[0069] The above drugs may contain antihistamines, anti-inflammatory agents, antibiotics, antiviral agents, antifungal agents, glucocorticoids, beta-blockers, calcium channel blockers, carbonic anhydrase inhibitors, angiogenesis inhibitors, immunomodulators, neurotrophic factors, growth factors, vitamins (D-pantothenic acid, vitamin B complex, etc.), or derivatives thereof. In addition, the solution may further contain, in addition to the D-pantothenic acid, nutrients, electrolytes, thickeners, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters (e.g., phosphates, citric acid), stabilizers (e.g., EDTA), preservatives (e.g., benzalkonium chloride, potassium sorbate), glycerin, alcohol, isotonic agents used in contact lenses (e.g., sodium salts, potassium salts), viscosity adjusters (e.g., hyaluronic acid, carboxymethylcellulose), etc.

[0070]

[0071] Meanwhile, the contact lens solution of the present invention can be formulated and used in various forms according to conventional methods. The pharmaceutical composition of the present invention can be formulated and used in various forms according to conventional methods. For example, it can be formulated as a sterilized eye drop, suspension, ophthalmic ointment, or ocular insert formulation, and depending on each formulation, it can be manufactured by including a pharmaceutically acceptable carrier, such as a buffer, a preservative, a solubilizer, an isotonic agent, a stabilizer, a lubricant, etc.

[0072]

[0073] Examples of the pharmaceutically acceptable carrier or diluent include, but are not limited to, boric acid, sodium salt, potassium salt, citric acid, glycerin, propylene glycol, sorbitol, edetate (EDTA), tetronic, hyaluronic acid, liquid paraffin, and saline solution, and all commonly used additives can be used.

[0074]

[0075] Meanwhile, the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects. The effective dosage level may be determined based on factors including the patient's health condition, type and severity of the wound, drug activity, drug sensitivity, administration method, administration time, administration route and excretion rate, treatment period, drugs used in combination or concurrently, and other factors well known in the medical field.

[0076]

[0077] As another specific example of the invention, the present invention is an invention for providing a medical device including a contact lens containing a pharmaceutical agent for treating an ophthalmic disease.

[0078] As a specific example of the invention, the medical device may be used for one or more ophthalmic diseases selected from the group consisting of glaucoma treatment, uveitis, ophthalmitis, diabetic retinopathy, cataracts, LASIK, LASEK, lens implantation, retinal disease, corneal ulcer, and dry eye, and in order to treat the disease, a pharmaceutical agent for treating the disease may be included together with a contact lens containing the drug of the present invention.

[0079]

[0080] Hereinafter, one or more specific examples will be described in more detail through examples. However, these examples are provided for illustrative purposes only and the scope of the present invention is not limited to these examples.

[0081]

[0082] Example 1. Confirmation of the feasibility of utilizing cetirizine drug release from contact lenses.

[0083] 1-1. Experimental method

[0084] The drug cetirizine was loaded into contact lenses to determine whether the contact lenses could release cetirizine.

[0085] Specifically, contact lenses were loaded with cetirizine by immersing them in a 0.25% cetirizine solution (600 μM), which has the same concentration as commercially available cetirizine eye drops, at room temperature for less than 8 hours, and then the changes in physical properties and release amount were measured.

[0086] At this time, the contact lenses used are as shown in Table 1 below.

[0087] FDA Group IIFDA Group IVSilicone hydrogelDailies (Alcon)SofLens (Bausch + Lomb)BioTrue (Bausch + Lomb)Moist (ACUVUE)Oasys oneday (ACUVUE)Oasys 2weekds (ACUVUE)Vita (ACUVUE)TruEye (ACUVUE)Clariti (Cooper Vision)MyDay (Cooper Vision)Avaira Vitality (Cooper Vision)Total-1 (Alcon)

[0088]

[0089] 1-2. Results

[0090] As a result of including cetirizine in a contact lens as described above, the diameter and moisture content corresponding to physical properties did not change significantly despite the inclusion of cetirizine, indicating that the physical properties of the contact lens are maintained even when cetirizine is included in the contact lens (Fig. 1).

[0091] In addition, as a result of confirming the release characteristics of cetirizine loaded in contact lenses, it can be confirmed in Table 2 below that although there is a large difference in the loading amount of cetirizine depending on the material of the contact lens, the release amount is all more than half (Fig. 2).

[0092] DepositedReleasedMOIST226.90 ± 7.03155.43 ± 1.73Aquacomfort61.67 ± 7.0026.10 ± 1.63Biotrue195.67 ± 17.44109.28 ± 7.31

[0093] In addition, as a result of comparing the release characteristics of cetirizine over time, it was confirmed that cetirizine loaded in the contact lens reached the maximum release amount after 120 minutes, as shown in Table 3 below (Fig. 3).

[0094] Time(min)MOISTAquacomfortBiotrue533.40 ± 9.1321.85 ± 1.5641.42 ± 3.541564.59 ± 6.8127.79 ± 1.8270.58 ± 0.0030100.47 ± 2.4624.80 ± 0.6089.30 ± 1.6760134.59 ± 12.2427.70 ± 2.7996.68 ± 1.88120148.38 ± 7.2226.46 ± 1.90106.43 ± 1.22240155.43 ± 1.7326.10 ± 1.63109.28 ± 7.31360151.97 ± 4.1126.41 ± 0.48105.17 ± 0.32

[0095]

[0096]

[0097] Example 2. Changes in the physical properties of cetirizine-containing contact lenses

[0098] In order to confirm changes in physical properties such as refractive power and visible light transmittance, changes in physical properties were confirmed when contact lenses were immersed in a 0.25% cetirizine solution (600 μM), which is the same concentration as commercially available cetirizine eye drops, at room temperature for less than 8 hours.

[0099] As a result, refractive power and visible light transmittance were not affected by cetirizine, and it was confirmed that even if cetirizine is loaded into a contact lens, the physical properties of the lens do not change, so it can be used as a drug carrier (Fig. 4).

[0100]

[0101] Example 3. Confirmation of the interaction between tear proteins and cetirizine.

[0102] To determine whether the effect and duration of the drug change when ophthalmic cetirizine interacts with tear proteins, the interaction between tear proteins and cetirizine was investigated.

[0103] Accordingly, in the present invention, Hen egg white lysozyme and Bovine serum albumin (BSA) were reacted with cetirizine, and the presence or absence of reaction was confirmed by measuring the energy generated when cetirizine interacts with proteins in tears using ITC (Isothermal titration calorimetry).

[0104] As a result, it was confirmed that cetirizine does not interact with tear proteins because neither hen egg white lysozyme nor bovine serum albumin interacted with cetirizine, and thus the function of cetirizine was not reduced (Fig. 5).

[0105]

[0106] Example 4. Experimental method for cetirizine release characteristics in various contact lenses

[0107] In addition to the commercially available contact lenses confirmed above, contact lenses have various materials, and in the present invention, the drug release amount and release rate when treated according to cetirizine concentration and containing solution for each contact lens material were compared.

[0108]

[0109] 4-1. Experimental materials and methods

[0110] Accordingly, various contact lenses shown in Table 4 below were immersed in a cetirizine-containing immersion solution at room temperature for approximately 8 hours to allow cetirizine to be absorbed. At this time, the concentration of cetirizine was treated at a concentration of 2.0 mM to 3.0 mM, and the immersion solution was divided into PBS (phosphate-buffered saline), MPS (Multi-Purpose Solution) containing a 20% solution of polyhexamethylene biguanide hydrochloride (PHMB-HCl), and a 30% solution of etidronic acid tetrasodium (HEDP 4Na).

[0111] FDA groupAdopted nameMonomerInon-ioniclow water contentLotrafilcon AFluoroether macromer + TRIS (trimethylsiloxysilane) + DMASenofilcon A3-methacryloxy-2-hydroxypropoxypropylbis(trimethylsiloxy)methylsilane + pHEMA + DMAIInon-ionichigh water contentHilafilcon BpHEMA + NVPNesofilcon ApHEMA + NVPOmafilcon AMPC + pHEMAIVionichigh water contentEtafilcon ApHEMA + MAASilicone hydrogelDelefilcon ASilicone hydrogel core (polydimethylsiloxane-based) with a surface hydrogel layer (polyamidoamine and polyacrylamide-acrylic acid)Senofilcon CPDMS macromer + NVP + pHEMASomofilcon APDMS macromer + NVP + pHEMAStenfilcon APDMS-MA + VMADMA: N,N-dimethylacrylamide, pHEMA: Polyhydroxyethylmethacrylate, NVP: N-vinyl-2-pyrrolidone, MPC: 2-methacryloyloxyethyl phosphorylcholine, MAA: Methacrylic acid, PDMS: Polydimethylsiloxane, PDMS-MA: Polydimethylsiloxane methacrylate, VMA: Vinyl methylacetamide

[0112]

[0113] 이때, 콘택트렌즈는 실험전 잔류 MPS의 제거를 위해 PBS에 24시간 가량 담가 세정한 이후 사용되었다.

[0114]

[0115] 4-2. Cetirizine drug release experiment method

[0116] To confirm the degree of cetirizine release, the contact lenses described in Table 3 were loaded with cetirizine by immersing them in 1 mL of solutions of PBS + cetirizine 2.0 mM, PBS + cetirizine 3.0 mM, MPS + cetirizine 2.0 mM, and MPS + cetirizine 3.0 mM at room temperature for less than 8 hours.

[0117] Thereafter, to confirm the drug release results, the cetirizine-loaded contact lens was transferred to 1 mL of PBS and a release experiment was performed. At this time, the PBS containing the contact lens was stirred in a stirrer rotating at 85 RPM, and 20 μl of the release solution was collected every 0, 15, 30, 60, 90, 120, and 180 minutes while stirred.

[0118] The emitted liquid samples collected at each time point above were diluted 10-fold in PBS, and the absorbance was measured at 231 nm using a UV-visible spectrophotometer, and the results were quantified using the cetirizine standard curve (Fig. 6).

[0119] The cetirizine release pattern was analyzed using the one-phase decay model by calculating the plateau (diameter), maximum release amount (μg / lens), and half-life (time to reach 50% of the maximum release amount, min).

[0120]

[0121] 4-3. Method for measuring the water content of contact lenses

[0122] To measure the moisture content of contact lenses, moisture on the contact lens surface was removed and the wet weight was measured. After drying in an 80°C incubator for 24 hours to completely evaporate the moisture, the dry weight was measured and the moisture content was calculated using the following mathematical equation (1).

[0123]

[0124]

[0125] 4-4. Measuring the diameter of a contact lens

[0126] The change in diameter of cetirizine-containing contact lenses was observed. The diameter was measured using an Optimec® Soft Contact Lens Analyzer.

[0127]

[0128]

[0129] Example 5. Experimental results of cetirizine release characteristics in various contact lenses.

[0130] 5-1. Results of cetirizine release

[0131] The release results of cetirizine for each lens were as shown in Table 5.

[0132] Contact lens materialConditionPlateau(Mean±Half-Width)Half Life(Mean±Half-Width)R 2Omafilcon ACet 2mM (PBS)144.2±4.97.93±1.690.9489Cet 2mM (MPS)129.15±5.8515.35±4.020.9494Cet 3mM (MPS)277.65±20.1529.94±8.140.9320Somofilcon ACet 2mM (PBS)156.4±5.921.68±3.560.9719Cet 2mM (MPS)127.3±12.720.52±7.580.8732Cet 3mM (MPS)253.9±17.234.88±8.060.9579Stenfilcon ACet 2mM (PBS)142.8±9.135.1±7.50.9643Cet 2mM (MPS)149.4±6.021.15±3.220.9639Cet 3mM (MPS)258.95±14.4529.11±6.230.9599Lotrafilcon ACet 2mM (PBS)109.77±10.3336.43±11.830.9350Cet 2mM (MPS)126.75±19.5557.7±22.310.9301Cet 3mM (MPS)179.05±9.0533.21±5.810.9748Delefilcon ACet 2mM (PBS)118.8±7.618.88±6.150.9180Cet 2mM (MPS)140.95±9.8530.36±7.850.9432Cet 3mM (MPS)220.6±5.126.28±2.320.9916Nesofilcon ACet 2mM (PBS)126.3±5.515.16±3.220.9436Cet 2mM (MPS)142.95±24.0547.8±17.660.8444Cet 3mM (MPS)207.9±3.56.93±0.710.9862Etafilcon ACet 2mM (PBS)170.6±6.313.6±2.640.9561Cet 2mM (MPS)147.3±5.523.76±3.480.9730Cet 3mM (MPS)283.6±14.020.49±4.440.9450Narafilcon ACet 2mM (PBS)59.14±6.2423.3±11.240.8407Cet 2mM (MPS)68.89±7.5337.12±13.570.9066Cet 3mM (MPS)117.4±6.522.3±5.690.9467Senofilcon A (1day)Cet 2mM (PBS)83.41±5.8819.86±6.580.9010Cet 2mM (MPS)144.7±28.974.63±32.470.9296Cet 3mM (MPS)182.35±9.5527.54±5.490.9676Senofilcon A (2 weeks)Cet 2mM (PBS)88.1±5.2717.2±5.250.9118Cet 2mM (MPS)128.9±12.935.73±12.810.9235Cet 3mM (MPS)186.75±6.2516.9±2.680.9692Senofilcon CCet 2mM (PBS)83.35±6.5911.26±5.360.8083Cet 2mM (MPS)101.43±10.1729.08±10.260.8492Cet 3mM (MPS)176.05±6.4519.47±3.340.9691Hilafilcon BCet 2mM (PBS)126.3±5.515.16±3.220.9436Cet 2mM (MPS)220.1±2.312.28±0.620.9958Cet 3mM (MPS)292.55±4.6523.57±1.440.9951.

[0133] As described in Table 5 above, it was found that drug binding and release characteristics showed clear differences depending on the material of the contact lens (Figs. 7 and 8).

[0134] In particular, it was confirmed that Hilafilcon B, Etafilcon A, Nesofilcon A, and Somofilcon A exhibited very favorable characteristics for loading and releasing cetirizine, with a plateau of over 250 μg at MPS 3 mM. However, silicone hydrogel series such as Narafilcon A showed a significantly low cetirizine loading amount of up to 116.8 μg, which is interpreted as being due to the limited binding force with cetirizine due to the hydrophobic nature of the lens material.

[0135]

[0136] 5-2. Results of changes in the diameter of cetirizine-containing contact lenses.

[0137] As described in Table 5 above, the plateau increase under high-concentration conditions (MPS 3 mM) was not linear. In most contact lenses, the plateau increased at 3 mM compared to 2 mM, but the rate of increase varied depending on the material.

[0138] Specifically, Hilafilcon B increased approximately 2.3-fold from 2 mM PBS to 126.1 μg and from 3 mM MPS to 292.5 μg, while Narafilcon A increased less than 2-fold from 58.0 μg to 116.8 μg.

[0139]

[0140] 5-3. Results of reaching maximum emission

[0141] Half-life is not always proportional to plateau, and sustained release characteristics require individual evaluation.

[0142] Specifically, Nesofilcon A had a high plateau (137.8 μg) at 2 mM MPS, but a very long half-life of 42.6 minutes. At 3 mM MPS, the half-life was abruptly shortened to 6.9 minutes, despite a plateau of 207.9 μg. This indicates the possibility that an initial burst release occurred at high concentrations. In addition, Lotrafilcon A and Senofilcon A (1 day) showed excellent sustained-release characteristics, with an increase in the plateau and an increase in the half-life simultaneously.

[0143]

[0144] 5-4. Results of adsorption and release of cetirizine

[0145] As a result of examining the adsorption and release amounts of cetirizine on contact lenses, the MPS condition showed generally better release characteristics than the PBS condition. In almost all contact lens materials, the MPS condition showed a higher plateau value than the PBS condition, and in particular, the plateau value tended to increase rapidly at 3 mM MPS. In addition, the half-life time also tended to be longer on average during MPS-based soaking, confirming that the soaking condition also affected the release sustainability (Figs. 9 and 10).

[0146]

[0147] 5-5. Results of changes in function rate and diameter after loading of cetirizine

[0148] It was confirmed that the moisture content of cetirizine was maintained relatively stably. In most materials, the moisture content change range was limited to ±2% even after treatment with 3 mM MPS + cetirizine, and in particular, it was confirmed that high-moisture content materials such as Nesofilcon A, Omafilcon A, and Somofilcon A maintained their moisture retention capacity. Although the moisture content of Etafilcon A decreased somewhat, it was expected that the impact would be minimal when conducting clinical trials due to the high initial moisture content due to the structural characteristics of the material.

[0149] However, in terms of diameter, hydrogel contact lenses showed a slight swelling result. In some silicone-based materials such as Narafilcon A, Senofilcon A (1 day), Senofilcon C, and Stenfilcon A, the diameter was observed to increase by approximately 0.4 to 0.5 mm after cetirizine soaking, but in most hydrogel materials (Etafilcon A, Hilafilcon B, Omafilcon A, etc.), the diameter change was within ±0.2 mm, which was confirmed to be a deformation within a clinically acceptable range (Figs. 11 and 12).

[0150]

[0151] Example 6. Comparative experiment on drug release characteristics of other drugs

[0152] Epinastine, an allergy-relieving drug similar to cetirizine, was incorporated into contact lenses. Epinastine was incorporated into MPS at the same concentration as cetirizine, and the differences in release amount and duration of release between the two drugs were quantitatively compared.

[0153]

[0154] 6-1. Experimental method

[0155] The experimental process was conducted in the same manner as the cetirizine drug release experiment in Example 4.

[0156] Specifically, the drugs used were cetirizine and epinastine, and the concentrations were 0.5 mM, 1.0 mM, 2.0 mM, and 3.0 mM, respectively, and the experiment was conducted using MPS solution. However, the contact lenses used were Etafilcon A and Narafilcon A, which had the most stable drug loading among the contact lenses that loaded cetirizine.

[0157] Before loading the drug onto the contact lenses, all contact lenses were washed by soaking them in PBS for approximately 24 hours to remove residual MPS.

[0158]

[0159] 6-2. Drug release experiment method

[0160] To confirm the degree of release of each drug, the Etafilcon A and Narafilcon A contact lenses were each immersed in 1 mL of an MPS solution containing PBS + cetirizine 0.5 to 3.0 mM cetirizine or epinastine for about 2 hours to load the drug.

[0161] Thereafter, to confirm the drug release results, the contact lenses loaded with cetirizine or epinastine were transferred to 1 mL of PBS and a release experiment was performed. At this time, the PBS containing the contact lenses was stirred in a stirrer rotating at 85 RPM, and 20 μl of the release solution was collected every 0, 15, 30, 60, 90, 120, and 180 minutes while stirred.

[0162] The emitted liquid samples collected at each time point above were diluted 10-fold in PBS, and the absorbance of cetirizine was measured at 231 nm and that of epinastine at 236 nm using a UV-visible spectrophotometer. The results were quantified using the cetirizine standard curve (Fig. 13).

[0163] The release patterns of cetirizine and epinastine were analyzed using the quantitative analysis model, using the one-phase decay model to calculate the plateau maximum release amount (μg / lens) and half-life (time to reach 50% of the maximum release amount, min).

[0164]

[0165] 6-3. Method for measuring the water content of contact lenses

[0166] To measure the moisture content of contact lenses, moisture on the contact lens surface was removed and the wet weight was measured. After drying in an 80°C incubator for 24 hours to completely evaporate the moisture, the dry weight was measured and the moisture content was calculated using Equation 1.

[0167]

[0168] 6-4. Measuring the diameter of a contact lens

[0169] The change in diameter of contact lenses containing cetirizine or epinastine was determined. The diameter was measured using an Optimec® Soft Contact Lens Analyzer.

[0170]

[0171] Example 7. Results of comparative experiment on drug release characteristics of other drugs

[0172] 7-1. Release results of cetirizine and epinastine

[0173] The release results of cetirizine and epinastine were as described in Table 6.

[0174]

[0175] Cetirizine and epinastine drug release one-phase-decay analysis Contact lens material Condition Plateau (Mean±Half-Width) Half Life (Mean±Half-Width) R 2 Etafilcon ACet 0.5mM38.80±2.814.85±N / A0.8558Cet 1.0mM65.66±3.756.44±2.840.9108Cet 2.0mM117.00±2.1011.41±0.990.9922Cet 3.0mM172.20±4.3013.96±1.690.9868EP 0.5mM44.60±1.4015.73±2.250.9813EP 1.0mM89.86±1.1413.59±0.810.9964EP 2.0mM194.85±33.8524.22±15.400.6739EP 3.0mM280.50±5.5015.42±1.370.9924Narafilcon ACet 0.5mM25.94±2.835.80±N / A0.7106Cet 1.0mM36.73±2.493.71±N / A0.8629Cet 2.0mM55.80±3.177.05±2.510.9088Cet 3.0mM82.98±6.8617.00±7.290.897EP 0.5mM21.39±0.6813.71±2.060.978EP 1.0mM36.88±0.9114.13±1.720.9875EP 2.0mM73.23±4.1421.71±5.430.9617EP 3.0mM104.40±4.4018.91±3.730.9742

[0176]

[0177] Table 6 above confirms that the total release of cetirizine was significantly higher than that of epinastine. Specifically, based on etafilcon A, cetirizine showed a plateau value that was approximately 15-70% higher than that of epinastine at all concentrations, and this was particularly noticeable under the 3.0 mM condition. Specifically, cetirizine was 280.5 μg / lens, while epinastine was 172.1 μg / lens, suggesting that cetirizine had a strong interaction with the contact lens material and high binding stability (Figs. 14 and 15).

[0178] In addition, it was confirmed that cetirizine has slow but sustained release characteristics. While the half-life of cetirizine was 15 to 20 minutes on average, that of epinastine was 4 to 14 minutes, confirming that cetirizine is continuously released without an initial burst, which is advantageous for maintaining a long-term effect. In particular, it was confirmed that even in highly hydrophobic materials such as narafilcon A, epinastine shows rapid release, but cetirizine maintains a relatively long half-life.

[0179] This is due to the effect of the release rate constant (K) of the drug. In the case of epinastine, it is suitable as a fast-acting drug because it has a large K value and is released quickly, but it was confirmed that it is not suitable for the contact lens system with sustained release of the drug that the present invention is trying to produce. On the other hand, cetirizine has a low K value and a large plateau, making it ideal for sustained release design.

[0180]

[0181] 7-2. Results of drug release efficiency verification

[0182] It was confirmed that cetirizine was adsorbed and released more drug than epinastine in both contact lenses. In particular, the release efficiency of cetirizine was approximately 1.5 to 2 times higher than that of epinastine in Etafilcon A, and both drugs showed high release efficiency in Narafilcon A, but cetirizine maintained a higher value more stably (Fig. 16).

[0183]

[0184] 7-3. Comparison of functional content and diameter changes after drug adsorption

[0185] The water content and diameter changes of contact lenses after each drug loading were examined. As a result, cetirizine maintained a relatively stable water content, but epinastine showed a sharp decrease in both water content and diameter at high concentrations.

[0186] Specifically, cetirizine showed little change in moisture content and stable diameter at concentrations of 0.5 to 2.0 mM, which indicates that cetirizine does not cause rapid deformation of the material structure, and although there was a slight decrease in moisture content at 3.0 mM, the diameter reduction was accompanied by an appropriate moisture content, so functional stability can be secured. On the other hand, in the case of epinastine, 3.0 mM epinastine in Etafilcon A significantly decreased to 47.2% in moisture content and 13.15 mm in diameter, which may indicate the possibility of structural shrinkage. This indicates that epinastine has a strong influence on the moisture distribution within the contact lens structure, and there is a possibility of moisture loss due to high hydrophobicity and strong drug-material interaction.

[0187] However, Narafilcon A exhibited excellent overall structural stability for both drugs. Specifically, diameter changes were maintained within ±0.2 mm under all conditions, and moisture content also showed no significant fluctuations. Therefore, the results above confirmed that Narafilcon A, due to its silicone hydrogel properties of low water retention and high structural stability, is an excellent material for drug loading (Fig. 17).

[0188]

[0189]

[0190] The present invention has been described above, focusing on preferred embodiments thereof. Those skilled in the art will appreciate that the present invention can be implemented in modified forms without departing from its essential characteristics. Therefore, the disclosed embodiments should be considered illustrative rather than limiting. The scope of the present invention is set forth in the claims, not the foregoing description, and all differences within the scope equivalent thereto should be construed as being encompassed by the present invention.

[0191]

[0192]

[0193] The present invention provides a method for loading a drug into a contact lens and a drug-loaded contact lens manufactured by the method, and an invention for the simple treatment of ophthalmic diseases using the same, and the purpose of the invention is to provide a medical device that can help with diseases such as allergic conjunctivitis and a pharmaceutical composition that can be used together with the medical device.

Claims

1. Contact lenses containing a pharmaceutical preparation for the treatment of allergic conjunctivitis.

2. A contact lens according to claim 1, wherein the pharmaceutical preparation comprises at least one pharmaceutical preparation selected from the group consisting of cetirizine, epinastine, olopatadine, ketotifen, azelastine, levocabastine, emedastine, and bepotastine.

3. In claim 1, A contact lens comprising at least one contact lens selected from the group consisting of a non-ionic-low water content hydrogel contact lens, a non-ionic-high water content hydrogel contact lens, an ionic-high water content hydrogel contact lens, and a silicone hydrogel contact lens.

4. A method for manufacturing a contact lens containing a pharmaceutical preparation comprising the following steps: (1) A step of treating a pharmaceutical preparation with a solution for contact lens application; (2) a step of immersing a contact lens in a solution treated with the pharmaceutical preparation produced in (1); and (3) A step of separating and washing the contact lens containing the pharmaceutical preparation in (2) above.

5. In claim 4, A method wherein the above contact lens solution comprises at least one contact lens solution selected from the group consisting of phosphate-buffered saline (PBS), multi-purpose solution (MPS), saline solution, Ringer's solution, Hank's balanced salt solution (HBSS), multipurpose disinfecting solution (MPDS), and artificial tears (Rewetting Drops).

6. A solution composition for containing a pharmaceutical preparation for treating allergic conjunctivitis in a contact lens.

7. In claim 6, A solution composition for containing the contact lens is at least one solution selected from the group consisting of phosphate-buffered saline (PBS), multi-purpose solution (MPS), saline solution, Ringer's solution, Hank's balanced salt solution (HBSS), multipurpose disinfecting solution (MPDS), and artificial tears (Rewetting Drops).

8. In claim 6, The solution composition for containing the above contact lens comprises 10 to 30 wt% of a polyhexamethylene biguanide hydrochloride (PHMB-HCl) solution, 10 to 30 wt% of an etidronic acid tetrasodium (HEDP 4Na) solution, and 40 to 80 wt% of PBS (phosphate-buffered saline). Solution composition.

9. In claim 6, A solution composition for containing the above contact lens further comprises at least one pharmaceutical agent selected from the group consisting of an antihistamine, a mast cell stabilizer, a steroid eye drop, and a non-steroidal anti-inflammatory agent.

10. In claim 9, A solution composition, wherein the pharmaceutical agent is included in a concentration of 1 to 5 mM in a solution composition for inclusion in the contact lens.

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