KR20230080854A - pH-responsive hydrogel contact lens for drug delivery and manufacturing method thereof - Google Patents

Abstract

The present invention relates to a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer and a method for manufacturing the same, wherein the drug is contained in a cellulose polymer that decomposes at a specific pH, so that the drug is not released when the lens is stored, but worn on the eye It relates to a pH-sensitive hydrogel contact lens for drug delivery that can enhance the therapeutic effect of ophthalmic diseases by controlling the drug to be released when the drug is released, and a method for manufacturing the same.

Description

Hydrogel contact lens for drug delivery using pH-responsive cellulose polymer and manufacturing method thereof {pH-responsive hydrogel contact lens for drug delivery and manufacturing method thereof}

The present invention relates to a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer and a method for manufacturing the same, wherein the drug is contained in a cellulose polymer that decomposes at a specific pH, so that the drug is not released when the lens is stored, but worn on the eye It relates to a pH-sensitive hydrogel contact lens for drug delivery that can enhance the therapeutic effect of ophthalmic diseases by controlling the drug to be released when the drug is released, and a method for manufacturing the same.

Contact lenses have been widely used because they have a wider field of view than glasses and can avoid cosmetic disadvantages caused by wearing glasses. Currently, contact lenses are used for vision correction and treatment as well as for beauty As the market expands, it continues to grow.

By directly contacting the eyeball, these contact lenses must maintain the safety and efficacy of the eye, while maintaining the transparency and surface wettability of the contact lens, and must transmit oxygen well toward the cornea of the eyeball. In other words, contact lenses should be designed in consideration of the clinical aspect of protecting the eyeball and cornea, the flow of the tear layer should be smooth, and excessive friction between the eyelid and the eye surface should be avoided. Biocompatibility, non toxicity, optical transparency, refractive index, surface wetability, water content suitable for the cornea, welling rate, oxygen permeability ( oxygen permeability).

Contact lenses as described above can be largely divided into hard contact lenses and soft contact lenses according to materials, and are classified into vision correction, treatment, and cosmetic contact lenses according to functions. Recently, hydrogels have been developed. Soft contact lenses are mostly used for vision correction and treatment of modern people.

On the other hand, it is most common to use eye drops or eye drops as a method of injecting drugs into the eye to solve problems such as various eye diseases or corneal damage. In the case of these eye drops or eye drops, it is inconvenient to administer frequently to maintain a certain concentration that can maintain the therapeutic effect, and the maintenance time of the effective therapeutic concentration is short as the drug is washed out of the eye by blinking of the eyelids However, there is a problem in that the low concentration of the drug continues for a long time, reducing the therapeutic effect by half.

As a substitute for these eye drops, ophthalmic ointments, which are viscous semi-solid preparations, are often used. Ointment-type drugs have a relatively long contact time on the eyeball compared to eye drops, so the chance of absorption of the drug increases, but after applying the ointment, the visibility is significantly lowered, and the ointment causes a foreign body sensation on the entire eyeball and around the eye, which is uncomfortable. feel like

In order to solve this problem, development of contact lenses that release drugs has been progressed. Since the drug loaded in the contact lens effectively passes through the cornea and is continuously released at an appropriate concentration, it can be applied to patients with dry eye syndrome and glaucoma to increase the therapeutic effect.

Previously proposed drug-releasing contact lenses release the drug immediately in the solution (physiological saline, lens preservative solution, etc.), making it impossible to wash before distribution, causing problems in product stability and effectiveness during distribution, and the duration of drug release is also 2-2. It is short, less than 3 hours, and has a disadvantage of low effectiveness. Accordingly, contact lens technology that releases drugs in a specific environment is being developed.

Korean Patent Registration No. 10-1860667 discloses a hydrogel contact lens for lasozyme-sensitive drug delivery and a method for manufacturing the same, and Korean Patent Publication No. 10-2019-0051318 discloses a hydrogel contact lens for temperature-sensitive drug delivery and its manufacturing method. A manufacturing method is disclosed.

However, the above techniques not only have a short drug release time, but also cause cloudiness due to the adsorption of lasozyme or release the drug by temperature response, so there is a concern that the drug may be released even when the lens is stored.

1. Korean Patent Registration No. 10-1860667: Hydrogel contact lens for lasozyme-sensitized drug delivery and its manufacturing method 2. Korean Patent Publication No. 10-2019-0051318: Hydrogel contact lens for temperature-sensitive drug delivery and its manufacturing method

The present invention was created to improve the above problems, and the drug is contained in a cellulose polymer that is decomposed at a specific pH so that the drug is not released when the lens is stored, but only when worn on the eye. By controlling the drug to be released in response to the pH The purpose is to provide a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer that can enhance the therapeutic effect of ophthalmic diseases and a manufacturing method thereof.

One example of a hydrogel contact lens for drug delivery using the pH-sensitive cellulose polymer of the present invention for achieving the above object is a hydrogel-based lens body; It is contained in the lens body and includes a drug-supported pH-sensitive particulate, wherein the pH-sensitive particulate is loaded with a cellulose polymer that decomposes in a specific pH environment and reacts at a specific pH to release the drug.

And another example of a hydrogel contact lens for drug delivery using the pH-sensitive cellulose polymer of the present invention for achieving the above object is a hydrogel-based lens body; and a drug layer formed on the inside of the lens body, wherein the drug layer is supported on a cellulose polymer that decomposes in a specific pH environment and reacts at a specific pH to release the drug.

The drug layer is formed by dispersing the drug in a pH-sensitive matrix solution in which the cellulose polymer is dissolved in a solvent.

The cellulosic polymer decomposes at pH 7.4 to 7.6.

The cellulose polymer is cellulose acetate phthalate (Cellulose Acetate Phthalate) or hydroxypropylmethylcellulose phthalate (Hydroxypropyl methylcellulose phthalate).

A coating film formed to cover the drug layer and controlling the rate and amount of the drug released from the drug layer; is further provided.

One example of a method for manufacturing a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer of the present invention to achieve the above object is to encapsulate a drug in a cellulose polymer that can be decomposed in a specific pH environment to produce pH-sensitive microparticles A synthesis step to obtain; a mixing step of adding and mixing the pH-sensitive fine particles to the polymer solution for the lens body; an injection step of injecting the polymer liquid for a lens body to which the pH-sensitive fine particles are added into an arm mold for forming a lens; and a forming step of combining the male mold for lens molding with the female mold and then polymerizing the mold, wherein the pH-sensitive microparticles react at a specific pH to release the drug.

The synthesis step is a) dissolving the cellulose polymer and the drug in an organic solvent to obtain a drug solution, b) adding a surfactant to the drug solution and then homogenizing to generate an oil-in-water emulsion, c ) The pH-sensitive fine particles are synthesized through the step of lyophilizing after removing the organic solvent in the oil-in-water emulsion.

Another example of a method for manufacturing a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer of the present invention for achieving the above object is a pH-sensitive matrix solution by dispersing a drug in a cellulose polymer that can be decomposed in a specific pH environment A synthesis step to obtain; A coating film forming step of forming a coating film by coating a polymer liquid for a coating film on a male mold for forming a lens; a drug layer forming step of coating the surface of the coating film with the pH-sensitive matrix solution to form a drug layer; an injection step of injecting a polymer solution for a lens body into an arm mold for forming a lens; and a molding step of combining the male mold with the female mold and then polymerizing the drug layer, wherein the drug layer reacts at a specific pH to release the drug.

The cellulose polymer is cellulose acetate phthalate (Cellulose Acetate Phthalate) or hydroxypropylmethylcellulose phthalate (Hydroxypropyl methylcellulose phthalate).

As described above, the present invention provides a material that releases a drug while the polymer decomposes in response to a specific pH by supporting a drug in a cellulose polymer that decomposes at a specific pH.

Accordingly, in the present invention, the drug is not released during distribution and storage of the lens, but when worn on the eye, the drug is released in response to the pH of the eyeball of 7.4 to 7.6. Therefore, since the drug can be controlled to be released in response to pH only when worn on the eye, the drug can be released at an appropriate concentration for a long time, thereby increasing the therapeutic effect of ophthalmic diseases.

1 is a cross-sectional view of a contact lens according to an example of the present invention;
2 is a perspective view of a contact lens according to an example of the present invention;
Figure 3 is a cross-sectional view of Figure 2,
4 is a schematic diagram of pH-sensitive particulates;
5 is a graph showing the results of drug release experiments of pH-sensitive microparticles at 25 ° C.
6 is a graph showing the results of drug release experiments of pH-sensitive microparticles at 37 ° C.
7 is a graph showing the results of drug release experiments of contact lenses at 37° C. and pH 7.4;
8 is a graph showing the results of drug release experiments of contact lenses at 4° C. and pH 5.4.

Hereinafter, a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer and a manufacturing method thereof according to a preferred embodiment of the present invention will be described.

Referring to FIG. 1, the hydrogel contact lens 10 for drug delivery using the pH-sensitive cellulose polymer of the present invention includes a hydrogel-based lens body 11 and pH-sensitive microparticles contained in the lens body 11 ( 12) is provided.

The lens body 11 is formed in a spherical shape. The shape of the lens body is the same as that of a conventional contact lens.

The lens body 11 contains 58 to 98% by weight of hydroxyethyl methacrylate (HEMA), 0.1 to 40% by weight of N-vinyl-pyrrolidone for hydrophilicity, and ethylene glycol as a crosslinking agent. It is formed by polymerizing a polymer liquid for a lens body containing 0.1 to 2.0% by weight of ethylene glycol dimethacrylate and 0.01 to 0.5% by weight of azobisisobutyronitrile (AIBN) as an initiator.

The lens body 11 formed by polymerization of the polymer liquid for the lens body has a hydrogel structure. A hydrogel is a material having a three-dimensional hydrophilic polymer network structure capable of containing a large amount of water. Hydrogels are composed of homopolymers or copolymers and form a structurally stable three-dimensional network structure with little fluidity.

The pH sensitive particles 12 are evenly dispersed in the lens body 11 of the hydrogel structure. The pH-sensitive microparticles may have an average diameter of 0.01 to 1000 μm. The pH-sensitive microparticles have pH-sensitivity to release a drug by being decomposed in a specific pH environment. For example, the pH-sensitive microparticles can be decomposed in response to pH 7.4 to 7.6.

pH-sensitive microparticles are formed by encapsulating a drug in a cellulose polymer. Here, the cellulose polymer serves as a matrix in which the drug is loaded. The cellulose polymer is decomposed in a specific pH environment and imparts pH sensitivity to the pH-sensitive microparticles. Cellulose acetate phthalate (CAP) or hydroxypropyl methylcellulose phthalate (HPMCP) may be used as the cellulose polymer.

As long as the drug that can be supported on the cellulose polymer can be used to treat ophthalmic diseases, there is no limitation. For example, the drug may be any one selected from Diquafosol, Cyclosporine, and Ofloxacin.

The hydrogel contact lens 10 for drug delivery using the pH-sensitive cellulose polymer of the present invention described above does not release the drug when stored in saline (usually around pH 5.5) or the like. When worn on the eyes, the drug is released as the pH-sensitive microparticles of the drug layer are decomposed in response to pH 7.4 to 7.6 in the eyeball. The drug released from the pH-sensitive microparticles passes through the hydrogel structured lens body and is exposed to the eye.

As described above, since the present invention is controlled to release the drug only at the pH of the condition of being worn on the eyeball, it is possible to release the drug at an appropriate concentration for a long time, thereby increasing the therapeutic effect of ophthalmic diseases.

Figures 2 and 3 show a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer according to another example of the present invention.

2 and 3, the hydrogel contact lens 10 for drug delivery using the pH-sensitive cellulose polymer of the present invention is formed on the inside of the hydrogel-based lens body 11 and the lens body 11 It has a coating film 13 and a drug layer 15 formed between the lens body 11 and the coating film 13.

The lens body 11 is the same as the lens body shown in FIG. 1 .

The coating film 13 is formed on the inner surface of the lens body 11 formed in a spherical shape and is a portion that contacts the eyeball. The coating film 13 is formed to cover the drug layer 15. The coating layer 13 serves to control the rate and amount of the drug released from the drug layer 15 .

The polymer liquid for the coating film for forming the coating film 13 is the same as the polymer liquid for the lens body. For example, the coating film contains 58 to 98% by weight of hydroxyethyl methacrylate (HEMA), 0.1 to 40% by weight of N-vinyl-pyrrolidone for hydrophilicity, and ethylene glycol dimethacrylate as a crosslinking agent. It is formed by polymerizing a polymer liquid for a coating film containing 0.1 to 2.0% by weight of ethylene glycol dimethacrylate and 0.01 to 0.5% by weight of azobisisobutyronitrile (AIBN) as an initiator.

The coating film 13 also has the same hydrogel structure as the lens body 11 . By adjusting the viscosity of the polymer solution for the coating film or adjusting the thickness of the coating film 13, the speed and amount of the drug passing through the coating film 13 can be changed.

The drug layer 15 is formed inside the lens body 11. This drug layer 15 is located between the lens body 11 and the coating film 13. The drug layer 15 may be formed in an annular shape around the central portion of the lens body 11 .

The drug layer 15 has a structure in which a drug is supported in a matrix of cellulose polymer. For example, the drug layer 15 may be formed by dispersing a drug in a pH-sensitive matrix solution in which a cellulose polymer is dissolved in a solvent.

When the above-described hydrogel contact lens 10 for drug delivery using the pH-sensitive cellulose polymer of the present invention is worn on the eye, the drug layer 15 is decomposed in response to pH 7.4 to 7.6 in the eye, and the drug is released. The drug released from the drug layer 15 passes through the coating layer 13 and is exposed to the eye.

On the other hand, unlike shown, the contact lens 10 of the present invention may omit the coating film. In this case, the contact lens 10 of the present invention consists of a lens body 11 and a drug layer 15 formed inside the lens body 11.

Hereinafter, a method for manufacturing a hydrogel contact lens for drug delivery using the pH-sensitive cellulose polymer of the present invention shown in FIG. 1 will be described.

The method for manufacturing a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer of the present invention includes a synthesis step of obtaining pH-sensitive microparticles by encapsulating a drug in a cellulose polymer that can be decomposed in a specific pH environment, and the pH-sensitive microparticles A mixing step of adding and mixing the polymer liquid for lens body, an injection step of injecting the polymer liquid for lens body with pH-sensitive fine particles added into an arm mold for lens molding, and combining the male mold for lens molding with the arm mold It includes a molding step of polymerization. Let's look at each step.

A-1. synthesis step

First, pH-sensitive microparticles are synthesized and prepared.

pH-sensitive microparticles are obtained by encapsulating a drug in a cellulose polymer that can be degraded by pH change. In order to synthesize these pH-sensitive microparticles, an oil in water (o/w) emulsion preparation method may be used.

Specifically, the synthesis steps for synthesizing pH-sensitive microparticles are a) dissolving a cellulose polymer and a drug in an organic solvent to obtain a drug solution, and b) adding a surfactant to the drug solution and then homogenizing to obtain an oil-in-water emulsion and c) removing the organic solvent in the oil-in-water emulsion and then freeze-drying it.

Any one or a mixture of two or more selected from methylene chloride, acetone, and ethanol may be used as the organic solvent.

The cellulose polymer may be cellulose acetate phthalate (CAP) or hydroxypropyl methylcellulose phthalate (HPMCP).

A wide variety of medications are available to treat eye diseases with medications. For example, the drug may be any one selected from Diquafosol, Cyclosporine, and Ofloxacin.

A drug solution may be obtained by dissolving 10 to 60 parts by weight of a cellulose polymer and 10 to 30 parts by weight of a drug with respect to 100 parts by weight of an organic solvent.

Next, a surfactant is added to the drug solution and homogenized to produce an oil-in-water emulsion.

Polyvinyl alcohol or poloxamer may be used as a surfactant. The surfactant is dissolved in a solvent such as distilled water, physiological saline, or phosphate buffered solution and used in the form of an aqueous solution. At this time, the surfactant may be dissolved in an amount of 0.1 to 10 parts by weight based on 100 parts by weight of the solvent.

A surfactant is added to the drug solution and then homogenized. As a homogenization method, an ultrasonic grinder or an ultra-high pressure homogenizer can be used.

Homogenization after adding a surfactant to the drug solution produces an oil-in-water (o/w) emulsion.

Next, the organic solvent in the oil-in-water emulsion is removed and freeze-dried.

The organic solvent can be removed by a rotary evaporation method or a nitrogen purging pressure reduction method. When the organic solvent is removed and freeze-dried, pH-sensitive microparticles in the form of fine powder are finally synthesized. The synthesized microparticles can be represented as shown in the schematic diagram of FIG. 4 .

A-2. mixing stage

Next, the pH-sensitive microparticles are added to the polymer solution for the lens body and mixed.

58 to 98% by weight of hydroxyethyl methacrylate (HEMA) as a polymer liquid for the lens body, 0.1 to 40% by weight of N-vinyl-pyrrolidone for hydrophilicity, and ethylene glycol di as a crosslinking agent A mixture of 0.1 to 2.0% by weight of ethylene glycol dimethacrylate and 0.01 to 0.5% by weight of azobisisobutyronitrile (AIBN) as an initiator may be used.

0.1 to 70 parts by weight of the pH-sensitive fine particles may be added to 100 parts by weight of the polymer solution for the lens body.

A-3. injection step

Next, the polymer liquid for the lens body to which the pH-sensitive fine particles are added is injected into the arm mold for forming the lens.

In general, in order to mold a contact lens, a male mold forming a convex surface and a female mold forming a concave surface are used.

A certain amount of polymer liquid for the lens body is injected into the concave surface of the arm mold.

A-4. molding step

After the male mold is combined with the female mold in a state where the polymer liquid for the lens body is injected into the female mold, the polymer liquid is polymerized and cured by photocuring or thermal curing.

In addition, when the male mold is separated from the female mold, the contact lens 10 containing the pH-sensitive particles 12 in the lens body 11 can be obtained.

Meanwhile, a method for manufacturing a hydrogel contact lens for drug delivery using the pH-sensitive cellulose polymer of the present invention shown in FIGS. 2 and 3 will be described.

The method for manufacturing a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer of the present invention includes a synthesis step of obtaining a pH-sensitive matrix solution by dispersing a drug in a cellulose polymer that can be decomposed in a specific pH environment, and A coating film formation step of forming a coating film by coating a polymer liquid for a coating film on a male mold, a drug layer formation step of coating a pH-sensitive matrix solution on the surface of the coating film to form a drug layer, and a lens body arm mold for lens molding It includes an injection step of injecting a polymer liquid and a molding step of polymerizing after combining the male mold with the female mold. Let's look at each step.

B-1: synthesis step

A pH-sensitive matrix solution is obtained by dispersing a drug in a cellulose polymer that can be degraded in a specific pH environment.

A cellulose polymer and a drug are dissolved in an organic solvent to obtain a pH-sensitive matrix solution.

Any one or a mixture of two or more selected from methylene chloride, acetone, and ethanol may be used as the organic solvent. Cellulose polymer and drug are the same as described above. A pH-sensitive matrix solution may be obtained by dissolving 10 to 60 parts by weight of a cellulose polymer and 10 to 30 parts by weight of a drug with respect to 100 parts by weight of an organic solvent.

The pH-sensitive matrix solution thus obtained has a structure in which a drug is supported in a matrix of cellulose polymer.

B-2: coating film formation step

Next, a coating film is formed by coating a polymer solution for a coating film on a male mold for forming a lens.

58 to 98% by weight of hydroxyethyl methacrylate (HEMA) as a polymer liquid for coating film, 0.1 to 40% by weight of N-vinyl-pyrrolidone for hydrophilicity, and ethylene glycol dimera as a crosslinking agent A mixture of 0.1 to 2.0% by weight of ethylene glycol dimethacrylate and 0.01 to 0.5% by weight of azobisisobutyronitrile (AIBN) as an initiator may be used.

The polymer liquid for the coating film may be coated on the male mold by a conventional method. For example, it may be coated by a pad printing method. The polymer liquid for the coated coating film forms a coating film.

B-3: drug layer formation step

Next, a pH sensitive matrix solution is coated on the surface of the coating film to form a drug layer.

The pH-sensitive matrix solution may be coated by a pad printing method. At this time, the pH-sensitive matrix solution may be coated only on a region other than the central portion and the magnetic edge portion of the coating film. In this way, the polymer liquid for drug coated on the coating film forms an annular drug layer.

B-4: injection step

Next, a certain amount of the polymer liquid for the lens body is injected into the arm mold for forming the lens.

58 to 98% by weight of hydroxyethyl methacrylate (HEMA) as a polymer liquid for the lens body, 0.1 to 40% by weight of N-vinyl-pyrrolidone for hydrophilicity, and ethylene glycol di as a crosslinking agent A mixture of 0.1 to 2.0% by weight of ethylene glycol dimethacrylate and 0.01 to 0.5% by weight of azobisisobutyronitrile (AIBN) as an initiator may be used.

B-5: molding step

Next, in a state where the polymer liquid for the lens body is injected into the female mold, the male mold is combined with the female mold, and then the polymer liquid is polymerized and cured by photocuring or thermal curing. In addition, when the male mold is separated from the female mold, a contact lens 10 having a drug layer 15 formed between the lens body 11 and the coating film 13 can be obtained.

Hereinafter, the present invention will be described through examples. However, the following examples are intended to specifically explain the present invention, and the scope of the present invention is not limited to the following examples.

<Example>

(1) Manufacture of the first contact lens

a. Synthesis of pH-sensitive microparticles

A drug solution was obtained by dissolving 30 parts by weight of cellulose acetate phthalate and 10 parts by weight of cyclosporin A drug with respect to 100 parts by weight of methylene chloride as an organic solvent.

Then, a surfactant solution was prepared by mixing 10 parts by weight of polyvinyl alcohol with respect to 100 parts by weight of distilled water. The surfactant solution and the drug solution were mixed at a volume ratio of 1:1 and then stirred using a high-speed stirrer to obtain an oil-in-water emulsion. The organic solvent in the oil-in-water emulsion was removed using a rotary evaporator, and then lyophilized to synthesize fine powdery pH-sensitive microparticles.

A total of five types of pH-sensitive microparticles were synthesized according to the amount of surfactant solution and drug solution.

b. 1st contact lens molding

2-hydroxyethyl methacrylate 96 wt%, N-vinyl-pyrrolidone 3 wt%, ethylene glycol dimethacrylate 0.8 wt%, 2 A polymer solution for a lens body was prepared by mixing 0.2% by weight of 2'-azobisisobutyronitrile. Then, 20 parts by weight of the pH-sensitive fine particles were added and mixed with respect to 100 parts by weight of the polymer solution for the lens body.

Using a pad printer, the polymer liquid for the lens body to which the pH-sensitive fine particles were added was injected into the female mold for forming the lens, and then the male mold was combined with the female mold. Then, a first contact lens having the structure of FIG. 1 was prepared by polymerization at 110° C. for 4 hours using a drying oven.

(2) Manufacture of the 2nd contact lens

a. Synthesis of pH-sensitive matrix solution

A pH-sensitive matrix solution was synthesized by dissolving 30 parts by weight of cellulose acetate phthalate and 10 parts by weight of cyclosporin A drug with respect to 100 parts by weight of methylene chloride as an organic solvent.

b. 2nd contact lens molding

2-hydroxyethyl methacrylate 96 wt%, N-vinyl-pyrrolidone 3 wt%, ethylene glycol dimethacrylate 0.8 wt%, 2 A polymer liquid for a coating film was prepared by mixing 0.2% by weight of 2'-azobisisobutyronitrile (2,2'-azobisisobutyronitrile).

In addition, a polymer liquid for a lens body was prepared with the same composition as the above polymer liquid for a coating film.

A polymer liquid for coating film was coated on a male mold for forming a lens using a pad printer to form a coating film. Then, a pH-sensitive matrix solution was coated on the coating film using a pad printer to form an annular drug layer.

In addition, after injecting the polymer liquid for the lens body into the female mold for lens molding, combining the male mold with the female mold, and then polymerizing at 110 ° C. for 4 hours using a drying oven, a second structure having the structure of FIG. Contact lenses were made.

<Characteristics of pH-sensitive microparticles>

The pH-sensitive microparticles were also evaluated for cyclosporin A encapsulation rate and loading rate, and the results are shown in Table 1 below. In Table 1, 'scale' means the mixing amount of the surfactant solution and the drug solution. In 'scale', 2:2 is a mixture of surfactant solution and drug solution of 2 ml each, 5:5 is a mixture of surfactant solution and drug solution of 5 ml each, and 10:10 is a mixture of surfactant solution and drug solution of 10 ml. 15:15 is a mixture of 15 ml each of the surfactant solution and the drug solution, and 20:20 is a mixture of 20 ml each of the surfactant solution and the drug solution.

Cyclosporine encapsulation properties No. Scale Particle diameter (nm) Encapsulation Conc. (mg/ml) Encapsulation Efficiency (%) Loading
Capacity (%) Before Freeze Drying after freeze drying Before Freeze Drying after freeze drying Before Freeze Drying after freeze drying Before Freeze Drying after freeze drying One 2:2 268.9±12.9 - 4.07 - 81.5 - 16.3 - 2 5:5 278.3±12.9 241.0±12.9 4.10 3.70 82.0 74.0 16.4 14.8 3 10:10 320.9±12.9 227.4±12.9 2.45 2.26 49.0 45.3 9.8 9.1 4 15:15 407.9±12.9 275.4±12.9 3.58 3.34 71.6 66.8 14.3 13.4 5 20:20 431.2±12.9 270.5±12.9 2.38 1.73 47.7 34.6 9.5 6.9

The particle size was measured using a particle size analyzer (ELSZ-2000 from Otsuka), and the drug concentration was obtained by dissolving the pH-sensitive fine particles in an organic solvent and then detecting the concentration of the drug using the HPLC-UV method.

Referring to the results of Table 1, it can be confirmed that the pH-sensitive microparticles are in the form of nanometer-sized microparticles. In addition, the pH-sensitive microparticles showed excellent encapsulation and loading rates in the scales in which the surfactant solution and the drug solution were mixed at 5ml:5ml and 15ml:15ml.

<Drug release test of pH-sensitive microparticles>

Drug release of the pH-sensitive microparticles was evaluated according to the temperature and pH environment. Experiments were conducted in PBS solutions at pH 5.4 and pH 7.4 containing 1% (w/w) sodium lauryl sulfate at 25°C and 37°C. No. 4 in Table 1 was used as the pH-sensitive fine particles.

Experimental results are shown in FIGS. 5 and 6 . 5 is an experimental result at 25 ° C, and FIG. 6 is an experimental result at 37 ° C.

Referring to Figures 5 and 6, it was found that the drug release rate was slow at pH 5.4 as designed, and in particular, the release was significantly suppressed at 25 ° C compared to 37 ° C.

On the other hand, at pH 7.4, the drug release rate was relatively fast, and the pH-sensitive microparticles were confirmed to have sensitivity at pH 7.4.

<Contact lens drug release test>

Drug release of the first and second contact lenses according to temperature and pH environment was evaluated. Experiments were conducted in PBS solutions at pH 5.4 and pH 7.4 containing 1% (w/w) sodium lauryl sulfate at 37°C and 4°C.

Experimental results are shown in FIGS. 7 and 8 . 7 is an experimental result at 37° C., pH 7.4, and FIG. 8 is an experimental result at 4° C., pH 5.4. 7 and 8, 'CAP_NC' means the first contact lens, and 'CAP_C' means the second contact lens.

Referring to FIG. 7, it was confirmed that the drug was continuously released for 24 hours in an environment of 37° C. and pH 7.4. In addition, it was found that there was a difference in the drug release rate depending on the presence or absence of the coating film. It was confirmed that the release rate of the drug can be controlled when the coating layer is present.

Referring to FIG. 8, it was confirmed that only less than 5% of the total drug content in the contact lens was released for 90 days in a solution condition of 4° C. and pH 5.4, which is a solution condition used for storage and distribution of contact lenses.

Through the above experimental results, it is expected that the contact lens of the present invention can be designed so that the drug is released in response to pH only when worn on the eye, thereby increasing the therapeutic effect of ophthalmic diseases by releasing the drug at an appropriate concentration for a long time. .

As described above, the present invention has been described with reference to an embodiment, but this is merely exemplary, and those skilled in the art will understand that various modifications and equivalent other embodiments are possible therefrom. Therefore, the true technical protection scope of the present invention should be determined by the technical spirit of the appended claims.

10: contact lens 11: lens body
13: coating film 15: drug layer

Claims (10)

a hydrogel-based lens body;
It is contained in the lens body and has a pH-sensitive particulate loaded with a drug;
The pH-sensitive microparticle is a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer, characterized in that the drug is supported on a cellulose polymer that is decomposed in a specific pH environment and reacts at a specific pH to release the drug. a hydrogel-based lens body;
And a drug layer formed inside the lens body,
The drug layer is a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer, characterized in that the drug is supported on a cellulose polymer that is decomposed in a specific pH environment and reacts at a specific pH to release the drug. The hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer according to claim 2, wherein the drug layer is formed by dispersing the drug in a pH-sensitive matrix solution in which the cellulose polymer is dissolved in a solvent. The hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer according to claim 1 or 2, wherein the cellulose polymer is decomposed at pH 7.4 to 7.6. The hydrogel for drug delivery using a pH-sensitive cellulose polymer according to claim 1 or 2, wherein the cellulose polymer is cellulose acetate phthalate or hydroxypropyl methylcellulose phthalate. Gel contact lenses. The hydrogel for drug delivery using a pH-sensitive cellulosic polymer according to claim 2, further comprising a coating film formed to cover the drug layer and controlling the rate and amount of the drug released from the drug layer. contact lenses. A synthesis step of obtaining pH-sensitive microparticles by encapsulating a drug in a cellulose polymer that can be degraded in a specific pH environment;
a mixing step of adding and mixing the pH-sensitive fine particles to the polymer solution for the lens body;
an injection step of injecting the polymer liquid for a lens body to which the pH-sensitive fine particles are added into an arm mold for forming a lens;
A molding step of combining a male mold for forming a lens with the female mold and then polymerizing the mold;
The pH-sensitive microparticles are a method for producing a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer, characterized in that to release the drug in response to a specific pH. The method of claim 7, wherein the synthesis step is a) dissolving the cellulose polymer and the drug in an organic solvent to obtain a drug solution, b) adding a surfactant to the drug solution and then homogenizing to obtain an oil-in-water emulsion Production of a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer, characterized in that the pH-sensitive microparticles are synthesized through the step of generating and c) removing the organic solvent in the oil-in-water emulsion and then freeze-drying method. A synthesis step of obtaining a pH-sensitive matrix solution by dispersing a drug in a cellulose polymer that can be degraded in a specific pH environment;
A coating film forming step of forming a coating film by coating a polymer liquid for a coating film on a male mold for forming a lens;
a drug layer forming step of coating the surface of the coating film with the pH-sensitive matrix solution to form a drug layer;
an injection step of injecting a polymer solution for a lens body into an arm mold for forming a lens;
Including; a molding step of combining the male mold with the female mold and then polymerizing it,
The drug layer is a method for producing a hydrogel contact lens for drug delivery using a pH-sensitive cellulose polymer, characterized in that to release the drug in response to a specific pH. The method according to any one of claims 7 to 9, wherein the cellulose polymer is cellulose acetate phthalate or hydroxypropyl methylcellulose phthalate. Manufacturing method of hydrogel contact lens for drug delivery.

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