RU2847424C1 - Contact lens for delivering medication - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: contact lens for delivering a drug comprises: a lens; a drug storage chamber element located at a distance from the centre of the lens; and a blocking element for controlling the release of the drug, connected to a part of the chamber element. The chamber-shaped element contains a channel-shaped element through which the drug moves from the chamber-shaped element and is released onto the eyeball. The blocking element is formed with a size capable of covering 50% to 95% of the area of the chamber-shaped element.

EFFECT: improved drug delivery efficiency and bioavailability.

9 cl, 20 dwg, 14 tbl, 4 ex

Description

Field of technology to which the invention relates

The present invention relates to a drug delivery contact lens with improved drug delivery efficiency and bioavailability.

Background of the invention

Medications used to treat ophthalmic diseases include ophthalmic solutions (eye drops) and ophthalmic ointments. For these existing ophthalmic medications, only approximately 7% of the ophthalmic solution is effectively utilized, with the remainder remaining for approximately 2 minutes before being flushed into the nasal cavity by tear circulation (Expert opinion on drug delivery 2006 3(2) 275-287). Additionally, ophthalmic ointments have the advantage of longer drug retention compared to ophthalmic solutions, but due to the nature of their formulation, they pose problems related to a foreign body sensation, irritation due to the adjuvants used, and the potential for interference with vision during blinking.

Consequently, the need has arisen to develop drug delivery vehicles with long drug retention times and ease of administration. Contact lenses for drug delivery have been developed as a technology to address this need. However, contact lenses typically developed for drug delivery currently utilize a polymer film containing the drug, which is placed and applied within the contact lens. These lenses still have problems. Specifically, highly concentrated polymers are required to form the film, and the FDA limits the amount of polymer used as a drug. Therefore, the choice of polymers is limited, or high-concentration polymers can only be used based on the results of toxicity tests based on very strict standards. Furthermore, using highly concentrated polymers poses challenges in lens formation, such as failure to maintain lens shape during application and poor adhesion to the lens. For water-soluble polymers, dissolution can cause irritation of the ocular mucosa.

In particular, for drug-delivery contact lenses, it is important that the drug is released continuously over the required period of time. However, polymer film contact lenses have a large polymer surface area exposed to the ocular mucosa, and the initial drug release rate rapidly increases due to the drug being dissolved by tears. Furthermore, each person's tear secretion volume varies, which can lead to different drug release patterns. This poses a problem: the drug release pattern is significantly influenced by the amount of tears.

Accordingly, the inventors of the present invention have realized a structure different from the existing drug delivery contact lenses in order to solve the above-mentioned problems in the art, and such a structure reduces the dosage and frequency of administration compared to ophthalmic solutions due to the prolonged release of the drug and provides a stable release of the drug compared to the drug delivery contact lenses known in the art, and therefore the drug delivery contact lens of the present invention was found to be optimal for the treatment of ocular diseases, and the present invention was completed.

Disclosure

Technical challenge

One aspect is to provide a contact lens comprising a main lens element, a chamber element for storing a drug located at a distance from the center of the main lens element, and a blocking element for controlling the release of the drug connected to a portion of the chamber element, where the chamber element comprises a channel through which the drug moves from the chamber element and is released onto the eyeball.

Another aspect is to provide an ophthalmic composition comprising an ophthalmic pharmacologically active drug and an auxiliary agent for controlling the release of the drug from at least one of a viscosity adjusting agent, an emulsifier and a stabilizer.

Technical solution

In one aspect, a contact lens is provided, comprising a main lens element, a chamber element for storing a drug located at a distance from the center of the main lens element, and a blocking element for controlling the release of the drug, connected to a portion of the chamber element, where the chamber element contains a channel through which the drug moves from the chamber element and is released onto the eyeball.

The drug delivery contact lens of the present invention, compared with existing ophthalmic solutions and drug delivery contact lenses, is characterized in that the contact lens is capable of controlling the release of a drug due to improved structure, improved bioavailability and stable release of the drug.

In particular, Fig. 1(a) and (b) or Fig. 2 show a drug delivery contact lens according to an example of the present invention.

Referring to Fig. 1 (a) and (b), the drug delivery contact lens of the present invention has a specific shape (e.g., a straight shape, etc.) within the main lens element and comprises a chamber-like element, which is a space for storing a small amount of an ophthalmologically pharmacologically active drug, a blocking element connected to a portion of the chamber-like element, and, as a portion of the chamber-like element, a channel-like element, through which the drug moves from the chamber-like element and is released onto the eyeball. The channel-like element may comprise an outlet through which the drug is released. The ophthalmologically pharmacologically active drug is introduced into the chamber-like element.

Referring to Fig. 2, the drug delivery contact lens of the present invention may further comprise a delivery channel in the channel-shaped element, through which the drug stored in the chamber-shaped element is transported to the outlet. The delivery channel may be used when finer control of drug release is required. Accordingly, the delivery channel may or may not be included in the drug delivery contact lens, depending on the shape of the chamber-shaped element.

As used herein, the term "primary lens element" refers to an element having a spherical surface so that it can be worn on the eye. The primary lens element material is a commonly used lens material, specifically, but not specifically limited to, a hydrophilic polymer or a hydrophobic polymer, and can be appropriately selected by those skilled in the art.

The hydrophilic polymer may comprise at least one selected from the group consisting of acacia gum, agar, alginic acid, carbomer, carrageenan, cellulose acetate, ceratonia, chitosan, chondroitin sulfate, dermatan sulfate, dextran, ethylcellulose, gelatin, guar gum, hydroxyethylcellulose, hydroxypropyl betadecax, hydroxypropyl cellulose, hypromellose, hypromellose acetate succinate, hypromellose phthalate, karaya gum, locust bean gum, methylcellulose, molasses, pectin, polyacrylamide, polycaprolactone, polyethylene oxide, polyethylene glycol, polyhydroxyethyl methacrylate, polyorthoester, polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, carboxymethylcellulose, sodium hyaluronate, tragacanth, triethyl citrate and xanthan gum.

The hydrophobic polymer may comprise at least one selected from the group consisting of acetyl alcohol, acetyl ether paraffin, acetyl tributyl citrate, aluminum monostearate, carnaubanaba, cellulose acetate, cellulose acetate phthalate, dibutyl sebacate, ethyl cellulose, glycerol monostearate, glycerol behenate, glycerol monooleate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil type 1, isopropyl palmitate, polycaprolactone, polyglycolide, polylactic acid, polylactide, polymethacrylate, polyoxyglyceride, shellac, stearic acid, stearyl alcohol, tributyl citrate, white wax, yellow wax and zein.

More specifically, the hydrophobic polymer may be at least one selected from the group consisting of, but not limited to, 2-hydroxyethyl methacrylate (2-HEMA), glycerol methacrylate, silicone hydrogel, and phosphorylcholine.

The primary lens element may optionally further comprise a vision correction element (a portion of the lens that corrects vision). The vision correction element is located in the center of the primary lens element and is positioned on the cornea to refract light entering the pupil, adjusting the diopter and thus correcting myopia, hyperopia, and the like. The drug-delivery contact lens of the present invention not only exhibits the effect of improving, preventing, or treating ophthalmological diseases by releasing a drug, but can also perform vision correction, which is a unique function of a contact lens.

As used herein, the term "chamber element" refers to a portion located away from the center of the lens's main unit and designed to contain a drug acting on the eyeball, particularly an ophthalmologically active drug. The chamber element can be formed as a concave structure within the contact lens. Additionally, one or more chamber elements can be formed within a single contact lens, and multiple chamber elements can accommodate the same drug or several different drugs.

Fig. 3 shows in detail the shape of the chamber element of the contact lens for drug delivery according to the present invention. Referring to Fig. 3, the chamber element can be implemented in the form of spaces for storing a small amount of drugs in the form of a plurality of straight lines (see (a) in Fig. 3), spaces for storing three individual drugs (see (b) in Fig. 3) and a space for storing one drug in a large amount (see (c) in Fig. 3) or in a connected form (see (d) in Fig. 3), but not limited to them, as long as the chamber element can effectively store drugs.

Specifically, the shape of the chamber-like element can be selected depending on the amount of drug to be applied, and the size can be adjusted. Adjustable size means that the diameter and/or depth of the selected chamber-like element, the length of the channel, etc., can be varied. This means that a contact lens mold can be manufactured by selecting the shape of the chamber-like element. Once the contact lens mold is formed, the drug can be administered using it, and a blocking element can be attached to form a drug-delivering contact lens (Fig. 4 (a)-(d)).

The chamber element may be comprised of a commonly used lens material and may be, in particular, at least one selected from the group consisting of, but not limited to, 2-hydroxyethyl methacrylate (2-HEMA), glycerol methacrylate, silicon hydrogel, and phosphorylcholine.

As used herein, the term "channel element" refers to the region through which the medication is transported to act on the eyeball and/or tears and serves to deliver the medication. In this regard, the medication can be slowly released from the channel element to act on the eyeball and/or tears. The channel element may comprise an outlet and/or a delivery channel, in particular, it may comprise only an outlet or include both an outlet and a delivery channel.

As used herein, the term "discharge orifice" refers to the portion where the drug is released, and "delivery channel" refers to the channel through which the drug moves from the chamber-like element to the channel-like element (discharge orifice) for release. In this regard, the delivery channel may be such that the drug stored in the chamber-like element is released onto the eyeball through the channel-like element (discharge orifice) at a constant rate. The length of the delivery channel and the size of the channel-like element can be adjusted by the shape of the chamber-like element and the size of the enclosing element. By adjusting the length of the delivery channel and the size of the channel-like element, the amount of drug released and the rate at which the drug is released can be determined.

As used herein, the term "blocking element" may refer to a portion capable of controlling the rate and mode of drug release. The blocking element is comprised of a commonly used lens material. The material may be, but is not limited to, at least one material selected from 2-hydroxyethyl methacrylate (2-HEMA), glycerol methacrylate, silica hydrogel, and phosphorylcholine.

The blocking element can be formed with a size capable of covering 50% to 95% of the area of the chamber-like element, and preferably, can be formed with a size capable of covering 70% to 95% of the area of the chamber-like element, but is not limited thereto. In particular, when the size or blocking ratio of the blocking element is within the above-mentioned range, a targeted drug release mode can be ensured.

The blocking ratio of the chamber element can be adjusted depending on the area of the chamber element covered by the blocking element, and the percentage of the area of the chamber element covered by the blocking element may indicate the blocking ratio of the chamber element. The blocking efficiency of the chamber element by the blocking element may be 50% or more and less than 100%, in particular, from 50% to 99%, from 50% to 97%, from 50% to 95%, from 50% to 93%, from 60% to 99%, from 60% to 97%, from 60% to 95%, from 60% to 93%, from 70% to 99%, from 70% to 97%, from 70% to 95%, from 70% to 93%, from 75% to 99%, from 75% to 97%, from 75% to 95%, from 75% to 93%, from 80% to 99%, from 80% to 97%, from 80% to 95%, from 80% to 93%, 85% to 99%, 85% to 97%, 85% to 95%, 85% to 93%, 90% to 99%, 90% to 97%, 90% to 95%, or 90% to 93%.

A drug delivery contact lens may be designed to release a drug at a constant rate. According to one example, the drug delivery contact lens of the present invention can control the release rate of a drug stored in a chamber-like element by adjusting the blocking ratio of the chamber-like element by the blocking element (the percentage of the area of the chamber-like element covered by the blocking element), in particular, the release rate control can be adjusted such that the drug stored in the chamber-like element is released at a constant rate. Accordingly, the drug delivery contact lens of the present invention is characterized in that the drug can be released in a controlled manner without simultaneous release at the initial stage. The controlled mode includes, but is not limited to, the zero-order model, the first-order model, the Higuchi model, the Noyes-Whitney model, the Korsmeyer-Peppas model, etc.

A drug delivery contact lens may be a sustained-release drug delivery contact lens. As used herein, the term "sustained release" means that the drug is slowly released into the body over an extended period of time by controlling the drug release mechanism/mode. Specifically, sustained release can be achieved by controlling the blocking factor of a chamber-like element using a blocking element.

The average thickness of the blocking element may be from 30 μm to 80 μm, preferably from 40 μm to 60 μm, but not limited thereto.

The chamber-shaped element may contain a drug and an auxiliary agent for controlling the release of the drug. The auxiliary agent for controlling the release of the drug may contain at least one selected from the group consisting of a viscosity-regulating agent, an emulsifier, a stabilizer, a pH-regulating agent, an isotonicity agent, and a preservative.

The viscous agent may include at least one selected from the group consisting of, but not limited to, xanthan gum, carbomer, carbopol, polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, povidone, polyethylene glycol, polyethylene glycol 400, polyethylene glycol 4000, glycerin, dextran, alginic acid, glucose, dextrose, and propylene glycol dicaprylate.

In relation to the total content of the ophthalmological composition containing the drug, the following can be used: a viscosity regulating agent content from 0.0015% w/v to 0.15% w/v xanthan gum, from 0.005% w/v to 0.5% w/v carbomer, from 0.002% w/v to 0.2% w/v carbopol, from 0.018% w/v to 1.8% w/v polyvinyl alcohol, from 0.005% w/v to 0.5% w/v hydroxyethyl cellulose, from 0.02% w/v to 2.0% w/v hydroxypropyl methylcellulose, from 0.014% w/v to 1.4% w/v methyl cellulose, from 0.005% w/v up to 0.5% w/v sodium carboxymethylcellulose, 0.04% w/v to 4.0% w/v povidone, 0.04% w/v to 4.0% w/v polyethyleneglycol, 0.08% w/v to 8.0% w/v polyethyleneglycol 400, 0.02% w/v to 2.0% w/v polyethyleneglycol 4000, 0.025% w/v to 2.5% w/v glycerol, 0.001% w/v to 0.1% w/v dextran, 0.01% w/v to 1.0% w/v alginic acid, 0.0009% w/v to 0.09% w/v glucose, from 0.00065% w/v to 0.065% w/v dextrose and from 0.0005% w/v to 0.05% w/v propylene glycol dicaprylate.

The emulsifier may include at least one selected from the group consisting of, but not limited to, polyoxyl 40 hardened castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyethylene hardened castor oil, polyoxyethylene hardened castor oil 60, polyoxyethylene hydrogenated castor oil, polyoxyl 35 castor oil, propylene glycol, poloxamer, polysorbate 80, tyloxapol, polyethyleneglycol 4000, povidone, macrogol glycerol hydroxystearate, and castor oil.

In relation to the total content of the ophthalmological composition containing the drug, it is possible to use an emulsifier content of from 0.0005% w/v to 0.05% w/v polyoxyl 40 hardened castor oil, from 0.002% w/v to 0.2% w/v polyoxyl 40 hydrogenated castor oil, from 0.001% w/v to 0.1% w/v polyoxyethylene-hardened castor oil, from 0.003% w/v to 0.3% w/v polyoxyethylene-hardened castor oil 60, from 0.001% w/v to 0.1% w/v polyoxyethylene hydrogenated castor oil, from 0.05% w/v to 5.0% w/v polyoxyl 35 castor oil, 0.03% w/v to 3.0% w/v propylene glycol, 0.0005% w/v to 0.05% w/v poloxamer, 0.01% w/v to 1.0% w/v polysorbate 80, 0.005% w/v to 0.5% w/v tyloxapol, 0.02% w/v to 2.0% w/v polyethyleneglycol 4000, 0.04% w/v to 4.0% w/v povidone, 0.05% w/v to 5.0% w/v macrogolglycerol hydroxystearate, and 0.0126% w/v to 1.26% w/v castor oil.

The stabilizer may include at least one selected from the group consisting of, but not limited to, sodium edetate hydrate, sodium citrate, povidone, polyvinyl alcohol, hydroxyethyl cellulose, methylcellulose, hydroxypropyl methylcellulose, polysorbate 80, tyloxapol, tromethamine, propylene glycol, sodium hydrosulfite, dibutylhydroxytoluene, sodium thiosulfate, hydroxypropyl gammadex, and aminocaproic acid.

In relation to the total content of the ophthalmological composition including the drug, it is possible to use a stabilizer content of from 0.005% w/v to 0.5% w/v sodium edetate hydrate, from 0.00294% w/v to 0.294% w/v sodium citrate, from 0.04% w/v to 4.0% w/v povidone, from 0.018% w/v to 1.8% w/v polyvinyl alcohol, from 0.005% w/v to 0.5% w/v hydroxyethyl cellulose, from 0.014% w/v to 1.4% w/v methyl cellulose, from 0.02% w/v to 2.0% w/v hydroxypropyl methyl cellulose, from 0.01% w/v up to 1.0% w/v polysorbate 80, 0.005% w/v to 0.5% w/v tyloxapol, 0.006% w/v to 0.6% w/v tromethamine, 0.03% w/v to 3.0% w/v propylene glycol, 0.001% w/v to 0.1% w/v sodium hydrosulfite, 0.00005% w/v to 0.005% w/v dibutylhydroxytoluene, 0.002% w/v to 0.2% w/v sodium thiosulfate, 0.015% w/v to 1.5% w/v hydroxypropyl gammadex, and 0.002% w/v to 0.2% w/v aminocaproic acid.

The pH adjusting agent may include at least one selected from the group consisting of hydrochloric acid, phosphoric acid, anhydrous sodium hydrogen phosphate, sodium sulfate, citric acid, sodium citrate, acetic anhydride, sodium acetate, sodium hydrogen carbonate, sodium hydroxide, monoethanolamine, borax, boric acid, dry sodium sulfite, sodium metabisulfite, sodium borate, and sodium lactate, but not limited to them.

In relation to the total content of the ophthalmological composition containing the drug, the content of the pH adjusting agent can be used, from 0.0027% w/v to 0.27% w/v hydrochloric acid, from 0.00288% w/v to 0.288% w/v phosphoric acid, from 0.00474% w/v to 0.474% w/v anhydrous sodium hydrogen phosphate, from 0.012% w/v to 1.2% w/v sodium sulfate, from 0.00005% w/v to 0.005% w/v citric acid, from 0.00294% w/v to 0.294% w/v sodium citrate, from 0.00007% w/v to 0.007% w/v acetic anhydride, 0.029% w/v to 2.9% w/v sodium acetate, 0.0005% w/v to 0.05% w/v sodium hydrogen carbonate, 0.00716% w/v to 0.716% w/v sodium hydroxide, 0.00052% w/v to 0.052% w/v monoethanolamine, 0.0011% w/v to 1.1% w/v borax, 0.02% w/v to 2.0% w/v boric acid, 0.002% w/v to 0.2% w/v dry sodium sulfite, 0.004% w/v to 0.4% w/v sodium metabisulfite, 0.00019% w/v to 0.019% w/v sodium borate, and 0.0002% w/v to 0.02% w/v sodium lactate.

The isotonicity agent may include at least one selected from the group consisting of, but not limited to, dextrose, glycerin, concentrated glycerin, mannitol, potassium chloride, sodium chloride, calcium chloride hydrate, magnesium chloride hydrate, D-sorbitol, D-sorbitol solution, glucose, and propylene glycol.

In relation to the total content of the ophthalmological composition including the medicinal product, it is possible to use an isotonic agent content of from 0.00065% w/v to 0.065% w/v dextrose, from 0.025% w/v to 2.5% w/v glycerin, from 0.026% w/v to 2.6% w/v concentrated glycerin, from 0.05% w/v to 5.0% w/v mannitol, from 0.0037% w/v to 0.37% w/v potassium chloride, from 0.0655% w/v to 6.55% w/v sodium chloride, from 0.00048% w/v to 0.048% w/v calcium chloride hydrate, 0.0003% w/v to 0.03% w/v magnesium chloride hydrate, 0.05% w/v to 5.0% w/v D-sorbitol, 0.066% w/v to 6.6% w/v D-sorbitol solution, 0.0009% w/v to 0.09% w/v glucose, and 0.03% w/v to 3.0% w/v propylene glycol.

The preservative may include at least one selected from the group consisting of, but not limited to, benzethonium chloride, methyl paraoxybenzoate, propyl paraoxybenzoate, chlorobutanol, benzalkonium chloride, and chlorocresol.

In relation to the total content of the ophthalmological composition containing the drug, the preservative content may be from 0.002% w/v to 0.1% w/v benzethonium chloride, from 0.0005% w/v to 0.05% w/v methyl paraoxybenzoate, from 0.0005% w/v to 0.05% w/v propyl paraoxybenzoate, from 0.25% w/v to 0.05% w/v chlorobutanol, from 0.002% w/v to 0.1% w/v benzalkonium chloride and from 0.0005% w/v to 0.05% w/v chlorocresol.

According to one example, the drug delivery contact lens of the present invention can control the release rate of a drug stored in a chamber-like element by adjusting the blocking ratio of the chamber-like element (the percentage of the chamber-like element area covered by the blocking element) and the combination of compositions/ratios of drug release-controlling adjuvants. In particular, the release rate can be controlled such that the drug stored in the chamber-like element is released at a constant rate. Therefore, the drug delivery contact lens of the present invention is characterized in that the drug is not released all at once at the initial stage and the drug can be released at a constant rate.

The drug delivery contact lens may be a sustained release drug delivery contact lens and, in particular, the sustained release may be achieved by controlling the blocking ratio of the chamber element by the blocking element and the combination of compositions/rates of the drug release controlling auxiliary agents.

The drug delivery contact lens can effectively realize the release rate control and/or sustained release effect compared with the ophthalmic solution, in particular, the drug delivery contact lens can continuously release the drug more efficiently than the ophthalmic solution, and therefore, the contact lens can exhibit more effective therapeutic efficacy with a smaller amount of the drug compared with the ophthalmic solution. For example, the drug delivery contact lens may exhibit more effective therapeutic efficacy even with the drug in an amount of 0.5 wt.% to 50 wt.% compared to the ophthalmic solution, in particular, it may exhibit effective therapeutic efficacy with the drug in an amount of 0.5 wt.% to 40 wt.%, 0.5 wt.% to 30 wt.%, 0.5 wt.% to 20 wt.%, 0.5 wt.% to 10 wt.%, 0.5 wt.% to 8 wt.%, 0.5 wt.% to 6 wt.%, 0.5 wt.% to 4 wt.%, 0.5 wt.% to 2 wt.%, 1 wt.% to 40 wt.%, 1 wt.% to 30 wt.%, 1 wt.% to 20 wt.%, 1 wt.% to 10 wt.%, from 1 wt.% to 8 wt.%, from 1 wt.% to 6 wt.%, from 1 wt.% to 4 wt.%, from 1 wt.% to 2 wt.%, from 2 wt.% to 40 wt.%, from 2 wt.% to 30 wt.%, from 2 wt.% to 20 wt.%, from 2 wt.% to 10 wt.%, from 2 wt.% to 8 wt.%, from 2 wt.% to 6 wt.%, or from 2 wt.% to 4 wt.% compared to an ophthalmic solution, but not limited to them. According to one example, as a result of evaluating the drug release using the drug delivery contact lens formulation of the present invention and an ophthalmic solution containing the same/similar composition containing a drug of the same/similar composition, it was confirmed that the contact lens formulation exhibits significantly better drug release results (drug release at a constant rate) than the ophthalmic solution (Tables 7 to 9 and Figs. 13 to 15), and it can be seen that when using the drug delivery contact lens of the present invention, the drug can be effectively delivered at a constant rate.

In addition, according to one example, as a result of evaluating the drug delivery into the blood and ocular tissues using the drug delivery contact lens formulation of the present invention and an ophthalmic solution containing a drug of the same/similar composition, it was confirmed that the bioavailability in the blood, cornea, conjunctiva, sclera or aqueous humor when using the drug delivery contact lens formulation increased by approximately 14 times, 37 times, 11 times, 11 times or 133 times, respectively, compared to the ophthalmic solution (Tables 10 to 14 and Figs. 16 to 20). Thus, when using the drug delivery contact lens composition of the present invention, it can be seen that even with an amount of 0.5 wt% to 10 wt% (blood: about 7.1%, cornea: about 2.7%, conjunctiva: about 9.1%, sclera: about 9.1% or intraocular fluid: about 0.75%) of the drug compared to an ophthalmic solution, effective therapeutic efficacy can be demonstrated.

The medicinal product may be an ophthalmologically pharmacologically active medicinal product.

The medicinal product may consist of at least one selected from the group consisting of, but not limited to, low molecular weight compounds, high molecular weight compounds, peptides and polypeptides.

The medicinal product may include at least one selected from the group consisting of, but not limited to, a therapeutic agent for dry eye syndrome, a therapeutic agent for glaucoma, an agent for lowering intraocular pressure, a therapeutic agent for visual impairment, an antibacterial agent, a therapeutic agent for allergic conjunctivitis, a therapeutic agent for blepharoconjunctivitis, a therapeutic agent for night blindness, a therapeutic agent for amblyopia, a therapeutic agent for eye inflammation, a therapeutic agent for cataracts, an antiviral drug, an iridosclerotic agent, a carbonic anhydrase inhibitor, and a therapeutic agent for macular degeneration.

A low molecular weight compound can generally refer to a material characterized by a molecular weight of 1000 or less. The low molecular weight compound may include, but is not limited to, at least one selected from the group consisting of hyaluronic acid in the form of a low molecular weight compound, calcium chloride, sodium chloride, glucose, trehalose, taurine, propylene glycol, cetrimide, asparagine, retinol palmitate, diquafosol, rebamipide, lifitegrast, timolol, dorzolamide, latanoprost, brimonidine, tafluprost, brinzolamide, travoprost, bimatoprost, betaxolol, carteolol, nipradilol, apraclonidine, pilocarpine, levobunolol, isopropyl-unoprostone, befunolol, acetazolamide, methazolamide, diclofenamide, unoprostone, verteporfin, levofloxacin, ofloxacin, Tobramycin, Moxifloxacin, Gatifloxacin, Oxytetracycline, Sulfamethoxazole, Glycyrrhizic Acid, Tosufloxacin, Lomefloxacin, Chloramphenicol, Dexamethasone, Tetrahydrozoline, Chlorpheniramine, Natamycin, Ciprofloxacin, Enoxolone, Fusidic Acid, Guaiazulene, Azulene, Erythromycin, Gentamicin, Sulfamethizole, Cefmenoxime, Norfloxacin, Micronomycin, Tetracycline, Olopatadine, Ketotifen, Alcaftadine, Bepotastine, Azelastine, Neostigmine, Pyridoxine, Epinastine, Naphazoline, Panthenol, Retinol, Pheniramine, Allantoin, Aspartic Acid, Cyanocobalamin, citazanolast, cromolyn, tranilast, pemirolast, lodoxamide, N-acetylaspartylglutamic acid, dried bilberry extract, beta-carotene, ascorbic acid, citrulline, tocopherol, riboflavin, fursultiamine, manganese, selenium, ergocalciferol, cefaclor, fluorometholone, tetryzoline, prednisolone, loteprednol, rimexolone, triamcinolone, bromfenac, ketorolac, bendazac, diclofenac, pranoprofen, flurbiprofen, pelubiprofen, neomycin, potassium iodide, sodium iodide, pirenoxine, thiamine, azapentacene, bendazac-lysine, nepafenac, acyclovir, ganciclovir, trifluridine, tropicamide, phenylephrine, aminocaproic acid, atropine, cyclopentolate, homatropine, zopolestat, fenofibrate, celecoxib, imrecoxib, polmacoxib, lumiracoxib, etoricoxib, and valdecoxib.

A high-molecular-weight compound generally refers to a polymer, and they can be classified into synthetic polymers and natural polymers. Additionally, a high-molecular-weight compound may refer to a compound, polymer, etc., different from a low-molecular-weight compound. A high-molecular-weight compound drug may contain, but is not limited to, carboxymethylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyacrylic acid, lanolin, dextran, hydroxyethylcellulose, polysorbate 80, polyvinyl alcohol, polyethyleneglycol, carbomer, guar gum, and hydroxymethylcellulose.

Peptides refer to a polymer in which amino acid units are linked artificially or naturally. Peptides can be classified into dipeptides, tripeptides, oligopeptides, polypeptides, etc., depending on the number of amino acid residues. In the present invention, the peptide-type drug may consist of only one peptide or two or more peptides; in particular, the peptide-type drug may be in a form consisting of only one peptide or in a form in which two, three, or four peptides are linked. The peptide-type drug may contain at least one selected from the group consisting of, but not limited to, chondroitin, cyclosporine, ranibizumab, aflibercept, polymyxin B, colistin, bemacizumab, liraglutide, and semaglutide.

For example, the medicinal product may comprise at least one selected from the group consisting of lifitegrast, timolol, dorzolamide, latanoprost, zopolestat, levofloxacin, pilocarpine, rebamipide, fenofibrate, olopatadine, fluorometholone, pirenoxine, acyclovir, liraglutide, semaglutide, cyclosporine or pharmaceutically acceptable salts thereof.

A drug-delivery contact lens can improve the rate of penetration of the released drug into the blood vessels or tissues of the eye (cornea, conjunctiva, sclera, and aqueous humor) and, in particular, can improve the rate of penetration of the drug into the blood vessels or tissues of the eye (cornea, conjunctiva, sclera, and aqueous humor) compared to an ophthalmic solution. Therefore, a drug-delivery contact lens can improve the bioavailability of the released drug.

The low molecular weight compound may include, but is not limited to, at least one selected from the group consisting of hyaluronic acid, calcium chloride, sodium chloride, glucose, trehalose, taurine, propylene glycol, cetrimide, asparagine, retinol palmitate, diquafosol, rebamipide, lifitegrast, timolol, dorzolamide, latanoprost, brimonidine, tafluprost, brinzolamide, travoprost, bimatoprost, betaxolol, carteolol, nipradilol, apraclonidine, pilocarpine, levobunolol, isopropyl unoprostone, befunolol, acetazolamide, methazolamide, diclofenamide, unoprostone, verteporfin, levofloxacin, ofloxacin, tobramycin, Moxifloxacin, Gatifloxacin, Oxytetracycline, Sulfamethoxazole, Glycyrrhizic Acid, Tosufloxacin, Lomefloxacin, Chloramphenicol, Dexamethasone, Tetrahydrozoline, Chloramphenicol, Dexamethasone, Tetrahydrozoline, Chlorpheniramine, Natamycin, Ciprofloxacin, Enoxolone, Fusidic Acid, Guaiazulene, Azulene, Erythromycin, Gentamicin, Sulfamethizole, Cefmenoxime, Norfloxacin, Micronomycin, Tetracycline, Olopatadine, Ketotifen, Alcaftadine, Bepotastine, Azelastine, Neostigmine, Pyridoxine, Epinastine, Naphazoline, Panthenol, Retinol, Pheniramine, Allantoin, Aspartic Acid, Cyanocobalamin, Acitazanolast, Cromolyn, Tranilast, Pemirolast, Lodoxamide, N-Acetylaspartylglutamic Acid, Dried Bilberry Extract, Beta-Carotene, Ascorbic Acid, Citrulline, Tocopherol, Riboflavin, Fursultiamine, Manganese, Selenium, Ergocalciferol, Cefaclor, Fluorometholone, Tetryzoline, Prednisolone, Loteprednol, Rimexolone, Triamcinolone, Bromfenac, Ketorolac, Bendazac, Diclofenac, Pranoprofen, Flurbiprofen, Pelubiprofen, Neomycin, Potassium Iodide, Sodium Iodide, Pirenoxine, Thiamine, Azapentacene, Bendazaclizine, nepafenac, acyclovir, ganciclovir, trifluridine, tropicamide, phenylephrine, aminocaproic acid, atropine, cyclopentolate, homatropine, zopolestat, fenofibrate, celecoxib, imrecoxib, polmacoxib, lumiracoxib, etoricoxib, valdecoxib, carboxymethyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyacrylic acid, lanolin, dextran, hydroxyethyl cellulose, polysorbate 80, polyvinyl alcohol, polyethylene glycol, carbomer, guar gum, hydroxymethylcellulose, chondroitin, cyclosporine, ranibizumab, aflibercept, polymyxin B, colistin, bevacizumab, liraglutide, semaglutide and their pharmaceutically acceptable salts.

A drug delivery contact lens can improve the penetration rate of the administered drug into the blood vessels or tissues of the eyeball (cornea, conjunctiva, sclera, and aqueous humor) compared to an ophthalmic solution.

According to one example, as a result of evaluating the bioavailability of a drug using the drug delivery contact lens formulation of the present invention and an ophthalmic solution containing a drug of the same/similar composition, it was confirmed that the drug bioavailability and the drug concentration retention time were significantly improved when using the contact lens formulation compared to using the ophthalmic solution (Tables 10 to 14 and Figs. 16 to 20), and therefore, it can be seen that when using the drug delivery contact lens of the present invention, the drug can be effectively delivered to the blood vessels and tissues of the eyeball.

Another aspect provides an ophthalmic composition comprising: an ophthalmic pharmacologically active drug and at least one auxiliary agent for controlling the release of the drug, selected from a viscosity-regulating agent, an emulsifier, and a stabilizer. The same parts described above also apply to the composition.

The ophthalmic pharmacologically active drug may be included in an amount of from 5% w/v to 20% w/v relative to the total content of the ophthalmic composition, but is not limited thereto.

The ophthalmic composition may additionally contain a pH adjusting agent, an isotonicity agent, or a preservative.

The ophthalmological composition can be used to improve, prevent or treat ophthalmological diseases, such as, preferably, dry eye syndrome, glaucoma, increased intraocular pressure, visual impairment, diseases caused by bacteria/viruses, allergic conjunctivitis, blepharoconjunctivitis, night blindness, amblyopia, ocular inflammation, cataract, pupillary disorders, diseases caused by carbonic anhydrase inhibitors and macular degeneration, but not limited to them.

As used herein, the term "improvement" means that the symptoms of ophthalmological diseases are improved upon administration of the ophthalmological composition according to the present invention.

As used herein, the term "prevention" refers to all actions to suppress or delay the symptoms of ophthalmological diseases by administering the ophthalmological composition according to the present invention.

As used herein, the term "treatment" means that the symptoms of ophthalmological diseases are beneficially modified by administering the ophthalmological composition according to the present invention.

[Implementation options]

Specific embodiments of a drug delivery contact lens according to the present invention will now be described with reference to Figs. 6-10. The contact lens according to the present embodiment comprises a drug storage structure located at a distance from the center of the contact lens and is designed to store the drug and deliver the drug to the eyeball of the contact lens wearer. In addition, the contact lens may further comprise a vision-correcting lens portion located in the center of the contact lens and refracting light.

Embodiment 1

Hereinafter, an embodiment of a contact lens according to the present invention will be described with reference to Fig. 6. However, descriptions of elements identical or similar to those described above may be omitted. Fig. 6 is a cross-sectional view schematically showing an embodiment of a contact lens according to the present invention. Referring to Fig. 6, the contact lens comprises a chamber-like element 122 formed as a concave structure on the contact lens and intended to store a drug in the concave structure; a blocking element 124 covering at least a portion of the chamber-like element 122; and a channel-like element formed by the blocking element 124 and intended to deliver a drug to the eyeball.

The chamber element 122 may be formed as a concave structure within the contact lens 12. For example, multiple chamber elements 122 may be formed within a single contact lens 12, and the multiple chamber elements 122 may store multiple different medications. In another example, the multiple chamber elements 122 may store the same medication.

Chamber element 122 can be formed with a predetermined volume. For example, chamber element 122 can be formed to store a drug in a volume of 1 µL to 2 µL. As another example, chamber element 122 can be formed with a volume corresponding to the volume of a single dose of the stored drug.

As an example of the above-described embodiment, the blocking element 124 can be made of silicon. The blocking element 124 can be formed from any of the same polymeric materials as the lens, including the hydrophilic polymeric material and the hydrophobic polymeric material described above.

Implementation option 2

Hereinafter, another embodiment of a contact lens according to the present invention will be described with reference to Figs. 7 to 9. However, descriptions of elements identical to or similar to those described above may be omitted. Fig. 7 is a plan view schematically illustrating another embodiment of the contact lens. Fig. 8 is a cross-sectional view schematically illustrating a cross-sectional view along line A-A' in Fig. 7. Referring to Figs. 7 and 8, a contact lens 13 includes a drug storage structure 140. The drug storage structure 140 comprises a chamber-shaped member 142+146+148 formed as a concave structure for storing a drug in the concave structure; a pumping channel 146 through which the drug contained in the chamber-shaped element 142+146+148, which is formed in the form of a concave structure for releasing the drug, can move to the outlet; and a blocking element 144 covering a part of the chamber-shaped element 142+146+148, where the blocking element 144 forms the outlet opening 148 by opening the end of the pumping channel for the drug.

The injection channel 146 is included in the chamber-like element 142+146+148 and directs the drug D contained in the chamber-like element 142+146+148 to the outlet opening 148. Fig. 8 illustrates an example in which the injection channel 146 and the part 142 of the chamber-like element are formed at the same height, but in an example not shown, the injection channel 146 can be formed with a height less than the part 142 of the chamber-like element.

As illustrated in Fig. 7, the blocking member 144 may be formed to cover the back surface of the contact lens 13 and the lower portion of the injection channel 146 may be opened to form an outlet 148.

(a) in Fig. 9 is a diagram showing an example of the outlet hole 148 when looking at the cross-section of the contact lens in the direction B in Fig. 7, and (b) in Fig. 9 is a diagram showing another example of the outlet hole 148. Referring to Figs. 7 and 8 and (a) in Fig. 9, the blocking member 144 opens the lower part of the pumping channel 146 to form the outlet hole 148. Thus, according to the example illustrated in (a) in Fig. 9, the outlet hole 148 releases the drug D through the lower surface of the contact lens 13.

However, according to the example of the outlet for the medicine illustrated in (b) in Fig. 9, the blocking member 144 can be formed so as to cover the entire lower surface of the pumping channel 146, but open the side end of the pumping channel 146, and thus, as illustrated in (b) in Fig. 9, the outlet hole 148 can be formed at the end of the pumping channel 146.

People blink their eyelids unconsciously. The user of the illustrated contact lens 13 may blink their eyelids unconsciously, and due to the pressure exerted by the eyelids moving the upper portion of the contact lens 13, the drug D stored in the chamber-shaped element 142+146+148 may be released through the outlet 148 and delivered to the user's eyeballs.

Embodiment 3

Hereinafter, another embodiment of a contact lens according to the present invention will be described with reference to Fig. 10. However, descriptions of elements identical or similar to those described above may be omitted. Fig. 10 is a plan view schematically illustrating another embodiment of the contact lens. Referring to Fig. 10, a contact lens 14 includes a drug storage structure 150. The drug storage structure 150 comprises a chamber member 152+156+158 formed as a concave structure for storing a drug in the concave structure; a pumping channel 156 included in the chamber member 152+156+158, which is formed as a concave structure and is for releasing a drug; and a blocking element 154 covering a portion of the chamber element 152+156+158, where the blocking element 154 forms an outlet opening 158 by opening the end of the injection channel for the drug.

According to the illustrated example, the chamber element 152+156+158 can be formed in the shape of a circle along the center of the contact lens 14. In this way, a single medicinal product can be stored in a large quantity.

In the illustrated lens 14, the outlet opening 158 may be formed on the lower surface of the contact lens 14 for releasing the drug D, as in the above-described examples, and the outlet opening 158 may be formed on the side of the injection channel 156 for releasing the drug through the end of the contact lens 14.

Positive effects

Because the drug delivery contact lens according to the present invention provides a constant and continuous release of the drug, it is expected that bioavailability will be enhanced by reducing the dose and frequency of administration compared to ophthalmic solutions in the prior art, reducing dose-related side effects, and increasing drug penetration into tissues. Furthermore, the drug delivery contact lens according to the present invention is easily applied to various drugs, has low irritation to the ocular mucosa, and is suitable for mass production due to its simple production method.

Description of graphic materials

Fig. 1(a)-(b) shows the structure of a contact lens for drug delivery according to an example of the present invention.

Fig. 2 shows the structure of a contact lens for drug delivery according to another example of the present invention.

Fig. 3(a)-(d) show in detail the shapes of the chamber element of the contact lens for drug delivery according to the present invention.

Fig. 4(a)-(d) show contact lens shapes for producing drug delivery contact lenses in accordance with the present invention.

Fig. 5 shows contact lenses for drug delivery depending on the blocking coefficients of the chamber element by the blocking element.

Fig. 6 is a top view schematically illustrating embodiment 1 of a drug delivery contact lens according to the present invention.

Fig. 7 is a top view schematically illustrating embodiment 2 of a drug delivery contact lens according to the present invention.

Fig. 8 is a cross-sectional view that schematically illustrates a cross-sectional view along line A-A' in Fig. 7.

(a) in Fig. 9 is a diagram showing an example of the outlet hole 148 when looking at the cross-section of the contact lens in the direction B in Fig. 7, and (b) in Fig. 9 is a diagram showing another example of the outlet hole 148.

Fig. 10 is a top view schematically illustrating embodiment 3 of a drug delivery contact lens according to the present invention.

Fig. 11 shows the results of the evaluation of the drug release test for the drug delivery contact lens depending on the blocking factors of the chamber element.

Fig. 12-15 show the results of the evaluation of drug release tests depending on the compositions of the drug release-controlling auxiliary agents contained in the chamber-shaped element.

Fig. 16 shows the results of in vivo pharmacokinetic studies in blood for a drug released using a drug delivery contact lens of the present invention.

Fig. 17 shows the results of an in vivo pharmacokinetic evaluation study in the cornea for a drug released using a drug delivery contact lens of the present invention.

Fig. 18 shows the results of an in vivo pharmacokinetic evaluation study in the conjunctiva for a drug released using a drug delivery contact lens of the present invention.

Fig. 19 shows the results of an in vivo pharmacokinetic evaluation study in the sclera for a drug released using a drug delivery contact lens of the present invention.

Fig. 20 shows the results of in vivo pharmacokinetic evaluation studies in aqueous humor for a drug released using a drug delivery contact lens of the present invention.

Method for invention

The present invention will now be described in more detail by means of examples or experimental examples. However, these examples or experimental examples are intended to illustrate the present invention, and the scope of the present invention is not limited to these examples.

Experimental example 1. Obtaining a contact lens for drug delivery, including a chamber-shaped element capable of storing the drug, a blocking element, etc.

To obtain a drug delivery contact lens according to the present invention, the following experiments were conducted.

Specifically, molds (lower and upper) were produced for the primary element of a drug-delivery contact lens, which includes a chamber element of various shapes. The mold was machined on a CNC 850 machine using grade 304 stainless steel.

Next, 15 ml of 2-hydroxyethyl methacrylate (2-HEMA) was applied to the lower mold, and then the upper mold was combined on top of the 2-HEMA to form the contact lens mold. After curing at 80°C for 1 hour using an OF-02 forced convection oven, the 2-HEMA was separated from the lower and upper molds, and the parts, except for the contact lenses, were removed to complete the main component.

A blocking element was then attached to the top of the main element. The blocking element was made of 2-HEMA and was available in various sizes capable of blocking part or the entire area (25%, 50%, 75%, 85%, 95%, 100%) of the chamber (Fig. 5).

Experimental example 2. Evaluation of drug release characteristics depending on the size of the blocking element (blocking film)

In order to evaluate the drug release characteristics depending on the size of the blocking element (blocking film), which is attached to the drug storage chamber element and blocks the release of the drug stored in the chamber element, drug delivery contact lenses Fig. 4(a) with different blocking coefficients were obtained.

In particular, drug delivery contact lenses were prepared that were coupled with blocking elements (blocking films) capable of blocking a plurality of straight chamber-shaped elements with an area ratio of 0%, 25%, 50%, 75%, 85%, 95% and 100% relative to the total area of the chamber-shaped element, a drug was introduced into each chamber element and the drug release characteristics were evaluated.

The drug release test was conducted by placing the drug-delivery contact lens in a Franz diffusion cell and evaluating the release. The test was conducted at a temperature of 37.0 ± 0.5°C and using a phosphate buffer solution with a pH of 7.4. A solution in which lifitegrast was dissolved in distilled water was introduced into the drug-delivery chamber of the contact lens, and the contact lenses were placed on the donor. In addition, the experiment was conducted in such a way that 5 ml of the drug-release solution was withdrawn from each container with a syringe and filled with the same amount of buffer solution at a given sampling time (0.5, 1, 1.5, 2, 3, 4, 5, 6 hours), after which 5 ml of the solution containing the collected drug was filtered through a syringe filter, 2 ml was placed in a vial and used as a test solution, and the resulting test solution was analyzed using high performance liquid chromatography (HPLC).

As a result of the above experiment, it was confirmed that the drug release behavior varies depending on the size of the blocking member (the blocking ratio of the chamber member) of the drug delivery contact lens, in particular, the drug release rate is affected by the blocking ratios of the chamber members, and it was confirmed that the effect of prolonged drug release is exhibited at a blocking ratio of 50% to 95%, but at a blocking ratio of 100%, the effect of prolonged release is not observed (Table 1 and Fig. 11). Based on the above results, in the case of the drug delivery contact lens of the present invention, a certain drug release level can be achieved by adjusting the blocking ratio of the chamber member using the blocking member (blocking film), and, in particular, it can be seen that the drug can be controlled to be released at a constant rate.

3-1. Evaluation of drug release control 1

In the drug delivery contact lens of the present invention, the following experiment was conducted to confirm whether the release of a drug introduced into a chamber-shaped element can be controlled using drug release-controlling auxiliary means.

Specifically, the drug release control aid was introduced along with the drug into a chamber-shaped element, which serves as a drug reservoir for the drug delivery contact lens. The chamber was configured as shown in (a) of Fig. 3, and a blocking element (blocking film) sized to block 75% of the total area of the chamber-shaped element was used.

A viscosity modifier, emulsifier, and/or stabilizer were used as auxiliary agents to control drug release. Hydroxypropyl methylcellulose (HPMC) was used as the viscosity modifier, poloxamer 188 was used as the emulsifier, and polysorbate 80 was used as the stabilizer. After obtaining samples in the ratios indicated in Table 2 below, drug release testing was conducted.

The drug release test was conducted by placing the drug-delivery contact lens in a Franz diffusion cell and evaluating it. The test was conducted while maintaining a temperature of 37.0 ± 0.5 °C and using a phosphate buffer solution with a pH of 7.4. A solution of the composition containing lifitegrast and auxiliary agents controlling the drug release was introduced into the chamber element of the drug-delivery contact lens, and the contact lens was placed on the donor to continue the experiment. In addition, the experiment was conducted in such a way that 5 ml of the drug-release solution was withdrawn from each container with a syringe, and the container was filled with the same amount of buffer solution at a given sampling time (0.5, 1, 1.5, 2, 3, 4, 5, 6 hours), after which 5 ml of the solution containing the collected drug was filtered through a syringe filter, 2 ml was placed in a vial and used as a test solution, and the resulting test solution was analyzed using HPLC.

As a result of the above experiment, it was confirmed that the effect of prolonged release of the drug can be achieved depending on the composition and ratio of the isotonicity agent, emulsifier and/or stabilizer introduced into the chamber of the contact lens to deliver the drug (Table 3 and Fig. 12).

Thus, based on the above results, it can be seen that the target drug release mode can be achieved by simultaneously applying the blocking coefficient of the chamber element with the blocking element and the drug release controlling auxiliary means.

3-2. Evaluation of drug release control 2

To confirm whether drug release-controlling adjuvants can control drug release for various drugs, the following experiment was conducted.

In particular, drug release control aids were introduced together with various types of drugs into a chamber-shaped element, which is a drug storage element in a contact lens for drug delivery. The chamber shape shown in (d) in Fig. 3 was used, and a blocking element (blocking film) of a size capable of blocking 92% of the total area of the chamber-shaped element was used. The drug release test was conducted according to the method described in Experimental Example 3-1, sampling was carried out at fixed times (1, 2, 4, 6 hours), the samples were analyzed using HPLC, and the examples were compared with an ophthalmic solution (comparative example).

The target drugs used were lifitegrast, latanoprost, and liraglutide, and the drug solutions administered into the chamber consisted of the compositions shown in Tables 4 through 6 below.

As a result of the above experiment, it was confirmed that the drug release pattern can be adjusted depending on the ratio of excipients in the drug composition solution, also for various types of drugs. Furthermore, when using the drug delivery contact lens of the present invention, it was confirmed that the drug can be released at a constant rate compared to an ophthalmic solution (Tables 7 to 9 and Figs. 13 to 15).

Thus, based on the above results, it can be seen that the target drug release mode can be achieved by simultaneously applying the blocking coefficient of the chamber element with the blocking element and the drug release controlling auxiliary means.

Experimental Example 4: Bioavailability Enhancement Test

To evaluate the in vivo pharmacokinetics of the drug released during use of the drug delivery contact lens of the present invention, the following experiments were conducted.

Specifically, approximately 6-month-old contact lens-wearing rabbits were used as test animals, and the test animals were subjected to an adaptation period under dilution conditions of 23±2°C, humidity of 50±10%, and a 12/12-hour light/dark cycle for 1 week before administration. A drug-delivery contact lens of composition No. 6 from Experimental Example 3-1 was used as the experimental group (Example 12), and a single administration of Xidra ophthalmic solution was performed as the control group (Comparative Example 4), and the results were compared. To confirm the drug distribution in the cornea, conjunctiva, sclera, and aqueous humor, which are the active sites of the drug, the rabbits were sacrificed, and the eyes were removed at different times for each formulation after administration. At each time point, two test subjects were sacrificed, and the number of ocular tissues was set at four. The cornea, conjunctiva, sclera, etc., were isolated from the removed eye, homogenized in distilled water, and the drug concentration in the sample was analyzed using LC-MS/MS. The area under the curve (AUC) of the concentration-time curve and the mean concentration were calculated based on the drug concentration in ocular tissue, and changes in the tissue distribution coefficient for the dose in the experimental group were compared with those in the control group and evaluated.

As a result of the pharmacokinetic analysis in blood, it was confirmed that the bioavailability was increased by 14 times when using the contact lens for drug delivery of the present invention (Table 10 and Fig. 16), compared with using the ophthalmic solution.

Further, as a result of the pharmacokinetic analysis in the cornea, it was confirmed that when the drug delivery contact lens of the present invention was used, the drug penetration rate into the cornea increased by 37 times compared with the control group (ophthalmic solution), and the drug concentration in the cornea was maintained for up to 3 hours after administration (Table 11 and Fig. 17).

Further, as a result of the pharmacokinetics analysis in the conjunctiva, it was confirmed that when using the drug delivery contact lens of the present invention, the drug penetration rate into the conjunctiva increased by 11 times compared with the control group (ophthalmic solution), and the drug concentration in the conjunctiva was maintained for a long time after administration (Table 12 and Fig. 18).

Further, as a result of the pharmacokinetic analysis in the sclera, it was confirmed that when using the drug delivery contact lens of the present invention, the drug penetration rate into the sclera increased by 11 times compared with the control group (ophthalmic solution) (Table 13 and Fig. 19).

Further, as a result of the pharmacokinetics analysis in the intraocular fluid, it was confirmed that when using the drug delivery contact lens of the present invention, the drug penetration rate into the intraocular fluid increased by 133 times compared with the control group (ophthalmic solution), and the drug concentration in the intraocular fluid was maintained for a long time (Table 14 and Fig. 20).

To summarize the above results, it can be seen that when using the drug delivery contact lens of the present invention, the penetration rate and bioavailability of drugs into the blood and various tissues of the eye (cornea, conjunctiva, sclera and intraocular fluid) can be significantly improved compared with existing ophthalmic solutions, and thus the drug delivery contact lens can be effectively used for the delivery of ophthalmic pharmacological agents and the treatment/prevention of ophthalmic diseases through it.

The foregoing description of the present invention is provided for illustrative purposes, and those skilled in the art to which the present invention pertains will appreciate that the examples and embodiments can be readily modified without altering the technical concept or fundamental features of the invention. Therefore, it should be understood that the foregoing examples are not limiting, but rather illustrative in all respects.

[Explanation of reference numbers]

12, 13, 14: contact lens

140, 150: structure for storing medicinal product

122, 142+146+148, 152+156+158: camera element

124, 144, 154: blocking element

146, 156: discharge channel

148, 158: outlet

200: the vision-correcting part of the lens

D: medicinal product.

Claims (13)

1. A contact lens for drug delivery, comprising: a lens; an element in the form of a chamber for storing a medicinal product, located at a distance from the center of the lens, and a blocking element for regulating the release of a drug, connected to a portion of the element in the form of a chamber, where the chamber-shaped element comprises a channel-shaped element through which the drug moves from the chamber-shaped element and is released onto the eyeball, wherein the blocking element is formed with a size that is capable of covering from 50% to 95% of the area of the chamber-shaped element. 2. A drug delivery contact lens according to claim 1, wherein the channel element comprises an outlet through which the drug is released. 3. A drug delivery contact lens according to claim 1, wherein the channel member comprises an outlet through which the drug is released and a delivery channel through which the drug is moved for release. 4. A contact lens for drug delivery according to any one of claims 1-3, wherein the blocking element is formed with a size that is capable of covering from 70% to 95% of the area of the chamber element. 5. A contact lens for drug delivery according to any one of claims 1-3, wherein the chamber element contains a drug and an auxiliary means for regulating the release of the drug. 6. The drug delivery contact lens of claim 5, wherein the drug release regulating agent is at least one agent selected from the group consisting of a viscosity regulating agent, an emulsifier, a stabilizer, a pH regulating agent, an isotonicity agent, and a preservative. 7. A contact lens for drug delivery according to any one of claims 1-3, wherein the drug consists of at least one agent selected from the group consisting of low molecular weight compounds, high molecular weight compounds, peptides and polypeptides. 8. A contact lens for delivering a medicinal product according to any of claims 1-3, wherein the medicinal product comprises at least one compound selected from hyaluronic acid, calcium chloride, sodium chloride, glucose, trehalose, taurine, propylene glycol, cetrimide, asparagine, retinol palmitate, diquafosol, rebamipide, lifitegrast, timolol, dorzolamide, latanoprost, brimonidine, tafluprost, brinzolamide, travoprost, bimatoprost, betaxolol, carteolol, nipradilol, apraclonidine, pilocarpine, levobunolol, isopropyl-unoprostone, befunolol, acetazolamide, methazolamide, diclofenamide, unoprostone, verteporfin, levofloxacin, ofloxacin, tobramycin, Moxifloxacin, Gatifloxacin, Oxytetracycline, Sulfamethoxazole, Glycyrrhizic Acid, Tosufloxacin, Lomefloxacin, Chloramphenicol, Dexamethasone, Tetrahydrozoline, Chlorpheniramine, Natamycin, Ciprofloxacin, Enoxolone, Fusidic Acid, Guaiazulene, Azulene, Erythromycin, Gentamicin, Sulfamethizole, Cefmenoxime, Norfloxacin, Micronomycin, Tetracycline, Olopatadine, Ketotifen, Alcaftadine, Bepotastine, Azelastine, Neostigmine, Pyridoxine, Epinastine, Naphazoline, Panthenol, Retinol, Pheniramine, Allantoin, Aspartic Acid, Cyanocobalamin, citazanolast, cromolyn, tranilast, pemirolast, lodoxamide, N-acetylaspartylglutamic acid, dried bilberry extract, beta-carotene, ascorbic acid, citrulline, tocopherol, riboflavin, fursultiamine, manganese, selenium, ergocalciferol, cefaclor, fluorometholone, tetryzoline, prednisolone, loteprednol, rimexolone, triamcinolone, bromfenac, ketorolac, bendazac, diclofenac, pranoprofen, flurbiprofen, pelubiprofen, neomycin, potassium iodide, sodium iodide, pirenoxine, thiamine, azapentacene, bendazac-lysine, nepafenac, Acyclovir, ganciclovir, trifluridine, tropicamide, phenylephrine, aminocaproic acid, atropine, cyclopentolate, homatropine, zopolestat, fenofibrate, celecoxib, imrecoxib, polmacoxib, lumiracoxib, etoricoxib, valdecoxib, carboxymethylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyacrylic acid, lanolin, dextran, hydroxyethylcellulose, polysorbate 80, polyvinyl alcohol, polyethyleneglycol, carbomer, guar gum, hydroxymethylcellulose, chondroitin, cyclosporine, ranibizumab, aflibercept, polymyxin B, colistin, bevacizumab, liraglutide, semaglutide and their pharmaceutically acceptable salts. 9. A contact lens for drug delivery according to any one of claims 1-3, wherein the lens includes a portion that provides vision correction.