KR102033594B1 - Manufacturing method of soft contact lenses for drug delivery - Google Patents

Abstract

The present invention adds a nanoparticle-sized drug carrier in a soft contact lens and delivers the drug to a target eye, thereby releasing the effective blood concentration appropriately for various diseases for a long time, thereby maximizing therapeutic efficacy. The present invention relates to a method for manufacturing a soft contact lens for delivery. To this end, the present invention adds a polymer carrier to a low-functional resin composition which is a raw material of a lens and polymerizes it to form a low-functional resin composition of a solid substrate. The low-function resin composition of the pulverized into nanoparticles, which are non-uniform dispersed particles on a colloid having a surface area of 1 to 900 nm, and the pulverized nanoparticles are added to the high-function contact lens composition and polymerized, and the polymerized high-function contact The lens composition is manufactured into a soft contact lens through a molding process and a process for producing the contact lens. It is characterized by.

Description

Manufacturing method of soft contact lenses for drug delivery

The present invention adds a nanoparticle-sized drug carrier in a soft contact lens and delivers the drug to a target eye, thereby releasing the effective blood concentration appropriately for various diseases for a long time, thereby maximizing therapeutic efficacy. A method of manufacturing a soft contact lens for delivery.

Drugs used for eye diseases or various treatments include eye drops (or eye drops) and eye ointments. In the case of these conventional drugs, eye drops are used effectively only about 7%, and the remainder is left for about 2 minutes by the tear circulation and then discharged into the nasal cavity.

In addition, the ophthalmic ointment has a longer residence time than eye drops, but has problems that irritate the eyes and interfere with vision.

Accordingly, the development of a drug delivery contact lens suitable for living beings, long drug retention time, and easy management is required. As a technology based on such a demand, a drug delivery vehicle of a hydrogel contact lens has been developed. .

The hydrogel of the hydrogel contact lens can contain the drug therein, and slowly dissolve the drug depending on the diffusion coefficient of the drug. The main advantage that can be obtained from hydrogels in the field of drug delivery is the ability to maintain a certain concentration of drug in surrounding tissues over time.

However, in spite of these advantages, the reason why the hydrogel is not practically applied to drug delivery is because of the low tensile strength, high water content and porosity, the difficulty of loading the hydrophobic drug and the relatively early dissolution characteristics. Because.

Therefore, the inventors of the present invention, as part of the research to solve the above conventional problems, by adding a drug carrier to the resin composition having a low water content to make a solid substrate after polymerization, it is pulverized into nano-sized particles to a high water content By adding in the contact lens having a conventional solution, it is possible to solve the conventional problems as well as to selectively deliver the drug to the target eyeballs to find the effective blood concentration for a long time according to various diseases and completed the present invention It was.

Korea Patent Publication No. 10-2004-0076324 (2004.10.30.) Korean Patent Publication No. 10-2005-0047300 (2005.06.29.) Korea Patent Registration No. 10-0557679 (2006.02.27.)

The present invention is to solve the problems of the prior art as described above, an object of the present invention is to selectively deliver the drug to the target eye to the drug for a long time by optimizing the effective blood concentration according to various diseases to improve the treatment efficacy and effect It is to provide a method for producing a soft contact lens for drug delivery that can be maximized, minimizing drug side effects.

In addition, the present invention prints and sprays a binder composition to which the drug carrier is added to the printing target area of the lens to maximize the therapeutic effect and effect according to various diseases, as well as to achieve a positive effect on the cosmetic side, various colors Another object of the present invention is to provide a method of manufacturing a patterned soft contact lens for drug delivery.

The problem solution means of the present invention for achieving the above object is to form a low-substrate resin composition of a solid substrate after the polymerization of the drug carrier to the low-function resin composition to be a raw material of the lens to form a polymer, The water-containing resin composition is pulverized into nanoparticles, which are non-uniform dispersed particles on a colloid having a surface area of 1-900 nm, the pulverized nanoparticles are added to the high-function contact lens composition and polymerized, and the polymerized high-function contact lens composition. It is characterized in that the manufacturing of the soft contact lens through a molding process and a process for manufacturing the contact lens.

In addition, the contact lens to form a color pattern by printing and spraying the binder composition to the desired printing target area, the binder composition is a pigment, a drug carrier and a solvent-based polyurethane (polyurethane), polyacryl (polyacryl) ), A urethane acrylate-based or an aqueous solvent-based polyurethane, a polyacryl, a urethane acrylate-based binder or a binder composed of a mixture of two or more It features.

In this case, the drug carrier, after dissolving the polymer in an organic solvent that can dissolve the polymer, by dispersing the solution in which the polymer is dissolved in an aqueous solution to which the emulsifier is added, the emulsifier and the polymer is coacervation (coacervation) And solidification reaction to form spherical nanoparticles.

The drug carrier may include an amphiphilic block copolymer polymer having hydrophilicity and hydrophobicity, and the drug carrier may be cationic, in which DNA, which is a non-viral gene carrier, is aggregated to a size of 50 to 200 nm. Characterized in that the polymer.

The drug delivery system as described above is characterized in that the drug delivery by the mechanism of the drug delivery system (DDS, drug delivery system).

In addition, the drug carrier, Bromo-deoxyuridine, F-Fluoro-uraci, Lododeoxyuridir, Dopamine nor-epinephrine, Retinoic acid, Paclitaxel, Substance P, Carmustine, Hormone agonist, Carboplatin, Isoniazid, Estradiol, Dopamine, Levodopa, Adenosine It includes a drug delivery polymer selected from maleate, Bunazosin, Levobunolol HCl, Betaxolol HCl, Dorzolamide hydrochloride, Brinzolamide, Acetazolamide, Methazolamide, Latanoprost, Travoprost, Bimatoprost, Tafluprost, Isopropyl unoprostone, Brimonidine and Pilocarpine.

On the other hand, the polymerization, after filtering the resin composition to which the drug carrier is added, by introducing a bulk polymerization method, the resin composition filtered in the contact lens mold is radically polymerized for 15 to 300 minutes at a temperature of 60-100 ℃ do.

The soft contact lens for drug delivery produced by the method of the present invention,

First, by selectively delivering the drug to the target eye, by optimizing the effective blood concentration for various diseases for a long time, it is possible to maximize the treatment efficacy and effect,

Second, to improve the prescription level of patients by improving the drug abuse that can occur during drug administration,

Third, by eluting the appropriate drug at the therapeutic level, the prevention and treatment efficiency of eye diseases is increased,

Fourth, the drug can stay in the thin film between the cornea and the lens for a long time, effectively absorbing the drug into the cornea,

Fifth, by printing and spraying the binder composition to which the drug carrier is added to the print object region of the contact lens to form a variety of color patterns, it can be expected a positive effect in terms of beauty.

1 is a block diagram showing a method for manufacturing a soft contact lens for drug delivery according to an embodiment of the present invention;
2 is a block diagram showing a method of manufacturing a color soft contact lens for drug delivery according to a further embodiment of the present invention;
Figure 3 is a block diagram showing a method for manufacturing a color soft contact lens for drug delivery according to another embodiment of the present invention.

As used herein, the term 'contact lens' refers to a structure that can be located on the eye and cornea of an individual.

The contact lens may be orthodontic, cosmetic, or therapeutic, including wound healing, delivery of drugs or Transferceutical, diagnostic assessment or monitoring, or UV blocking and reduction of visible or glare, or a combination thereof. As an ergonomic device that can provide advantages, the contact lens can be of any suitable material known in the art, and can be a soft contact lens, a hard contact lens or a hybrid contact lens, preferably with flexibility and fit It can be an excellent soft contact lens.

In the soft contact lens for drug delivery of the present invention, as shown in Fig. 1, after adding and polymerizing a drug carrier to a resin composition which is a raw material of a lens, a low water content resin composition of a solid substrate is formed. Was prepared by grinding into nanoparticles, which are non-uniform dispersed particles of colloids having a large surface area of 1 to 900 nm in size, and adding the pulverized nanoparticles to a high-function contact lens composition and polymerizing them through a molding process and a processing process. do.

As described above, preparing a soft contact lens by pulverizing the low-functional resin composition to which the drug carrier is added to the nanoparticle size, and then adding the crushed nanoparticles to the high-function contact lens composition again extends the drug sustain time. In order to facilitate the water content control, it is possible to increase the therapeutic efficacy and effect and to minimize the side effects of the drug.

In a further embodiment of the present invention, the contact lens is a binder composition in a region to be printed that wants the contact lens in order to be able to exert a positive effect in terms of cosmetic as well as the purpose of vision correction. Color soft contact lenses for drug delivery can be manufactured by printing and spraying to form a color pattern.

In the color soft contact lens, as shown in FIG. 2, a drug carrier is added and polymerized to a resin composition which is a raw material of a lens to form a low-performance resin composition of a solid substrate, and then the low-function resin composition is 1 to 900 nm. After crushing to size, the pulverized nanoparticles were added to the high-function contact lens composition and polymerized to produce a soft contact lens by molding and processing, followed by printing and spraying a binder composition on the printing target area of the soft contact lens to produce color. Manufactured by forming a pattern, or

As shown in FIG. 3, the color soft contact lens is formed by adding a drug carrier to a resin composition that is a raw material of a lens and polymerizing the same to form a low-performance resin composition of a solid substrate, and then, the low-function resin composition is 1 to 900 nm. It can be prepared by pulverizing to the nanoparticle size of, the pulverized nanoparticles are mixed with the binder composition, printed and sprayed, and then polymerized soft contact lenses.

Here, the binder composition may be composed of a composition used in the manufacture of a conventional color contact lens, the present invention after adding and polymerizing a drug carrier to the binder composition to form a low-function resin composition, the low-function resin composition Is pulverized to a nanoparticle size, and the pulverized nanoparticles are added and polymerized to a high-function contact lens composition to produce color soft contact lenses.

For example, the binder composition may be a pigment to which each color is given, and a polyurethane, a polyacryl, a urethane acrylate-based, or an aqueous solvent-based polyurethane based on a drug carrier and an oil-based solvent. (polyurethane), polyacryl (polyacryl), urethane acrylate (urethane acrylate) any one or a binder composed of a mixture of two or more may be a compounded composition. In this case, the pigment may be selected depending on the pattern to be formed or the like.

On the other hand, the drug carrier is added and polymerized solid substrate low-function resin composition is formed by pulverizing to a nanoparticle size of 1 to 900nm, such nanoparticles are very weak because of the specific particle size of the blood vessels and loose structure There is an advantage that can easily pass through the blood vessels in the tissues such as inflammation (EPR effect: Enhanced Permeability and Retention effect). In addition to the size characteristics of the nanoparticles, a receptor for a specific antigen may be attached to the nanoparticles to increase selective delivery efficiency.

In addition, the present invention selectively delivers the drug to the target eye, optimizing the effective blood concentration for a long time, for example, stye, dry eye, conjunctivitis, corneal haze, scleritis, cataracts, uveitis, glaucoma, etc., thereby maximizing therapeutic efficacy and effect Of course, the drug delivery system (DDS, drug delivery system) to minimize the side effects of the drug is characterized in that the delivery of the drug.

On the other hand, the resin composition that is the raw material of the lens in the present invention is not particularly limited as long as it is a resin composition that is typically used to manufacture soft contact lenses, for example, a resin composition containing a resin, a polymerization initiator, an additive, and the like may be used. have.

The resin used in the preparation of the low-function resin composition and the high-function contact lens composition of the present invention is, as an embodiment, 2-hydroxyethyl methacrylate, polyvinyl pyrroridone, glycerin meta Acrylate (glyceryl methacrylate), diacetone acrylamide, polyvinyl alcohol (polyvinyl alcohol, PVA) and the like can be used, but are not necessarily limited thereto.

In a further embodiment of the present invention, the resin used in the preparation of the low-function resin composition and high-function contact lens composition, such as polymethyl methacrylate, polystyrene, polycarbonate, and the like It can be prepared from a rigid material, including a combination of In addition, a flexible material including a combination of these may be used, such as hydrogel, silicon, acrylic, fluorocarbons, and the like.

Meanwhile, the resin composition may include water molecules in addition to the drug carrier, and the resin composition containing the water molecule and the low molecular weight resin composition in which the drug carrier is mixed and polymerized are pulverized to nanoparticle size and then pulverized. The prepared nanoparticles were added to the high-function contact lens composition and injected into a mold having concave and convex surfaces corresponding to the shape of the contact lens, and then gradually heated up at 40 to 60 ° C and 15 to 300 at a temperature of 60 to 100 ° C. Polymerize for a minute.

The reason for gradually raising the temperature in the polymerization process, since the bubble is generated in the contact lens when the polymerization at too high temperature from the beginning, causing a defective product, to gradually increase the temperature in order to prevent this.

As described above, polymerization may be a problem at temperatures below 60 ° C. or above 100 ° C., so that the temperature is gradually increased from 70 ° C. and maintained at 90 ° C. for 15 to 300 minutes, followed by polymerization to form a lens. Through the process and processing to obtain a lens according to the invention. The machining process can be achieved, for example, by smoothly cutting the remaining portions except the optical zone.

Herein, the polymerization is performed by filtering the resin composition to which the drug carrier is added, and then introducing the so-called 'bulk polymerization' without using a solvent, and then filtering the resin composition filtered into the contact lens mold at a temperature of 60 to 100 ° C. It may consist of a mechanism for radical polymerization under 15 to 300 minutes. For example, radical polymerization may be performed using azobisisobutyronitrile (AIBN), which is a radical initiator.

On the other hand, as an embodiment for producing a low molecular weight resin composition of the solid substrate formed by mixing and polymerizing the drug carrier and the resin composition according to an embodiment of the present invention, the spontaneous emulsion solvent method (spontaneous emulsion solvent) diffusion), a method for forming nanoparticles through a copolymer, and a method for forming nanoparticles using a complex reaction of an ionic polymer. At this time, when the size of the nanoparticles exceeds 900nm it is difficult to achieve the object of the present invention can not easily reach the target position, if less than 1nm problem occurs that the treatment efficiency is sharply lowered, The size is preferably 1-900 nm.

The spontaneous emulsion solvent diffusion method is to dissolve the polymer in an organic solvent in which the polymer can be dissolved, and then to disperse it in an aqueous solution to which a certain amount of emulsifier is added to obtain nanoparticles. In the first step, when the polymer solution is dispersed in an emulsion solution, an emulsion droplet of 1 to 5 micron size of the polymer solution spontaneously forms at the interface.

In the second step, the emulsion diffuses in an aqueous solution having low affinity for the polymer, and coacervative of the polymer occurs with the emulsifier as the concentration of the organic solvent increases at the interface.

In the final stage, solidification of the polymer takes place to form spherical nanoparticles, which are instantaneous and spontaneous. In this case, the size of the nanoparticles varies depending on the stabilizer, the type of polymer and the dispersion method, and the like, and the drug agent to be mounted in the nanoparticles is preferably dissolved in an organic solvent together with the polymer.

In case of applying the spontaneous organic solvent diffusion method, nanoparticles of ophthalmic material are sprayed, and then melted using an emulsified solvent, and then grafted to hydration in the process and soft contact such as water spraying. It is contained in the lens. This is to change depending on the time of hydration while changing the moisture content.

In the method of forming nanoparticles through the copolymer, the nanoparticles are copolymerized together in the copolymer of the soft contact lens at the time of manufacturing or designing the soft contact lens so that the drug is maintained for a certain time as the nanoparticles are added thereto. The system can be manufactured or designed to maintain a constant blood concentration in a slow release where the drug is slowly eluted.

The soft contact lens of the present invention prepared as described above is used in the treatment of eye diseases while maintaining a constant blood concentration of nanoparticle-sized drugs by a mediator, ie, a drug delivery system (DDS), that delivers a medicinal component to the eye. You can increase the effect.

In the method of forming nanoparticles through the copolymer, the drug carrier is an amphiphilic block copolymer polymer (or an amphiphilic polymer, ie, particles having hydrophilic properties and particles having hydrophobic properties simultaneously in a single molecule of the water-soluble polymer (or Amphiphilic polymer).

The amphiphilic polymer has a property that the hydrophobic polymer block forms a self-assembly in an aqueous solution but still dissolves in water.

On the other hand, the copolymer (amphiphilic block copolymer) is combined in an aqueous solution to form a micelle (micelle) consisting of an internal hydrophobic region and an external hydrophilic region, the micelle encloses a hydrophobic drug, the hydrophilic block is the outer It wraps around and prevents it from being rapidly absorbed by the reticuloendothelial system (RES) or other organs. As a result, the polymer micelles have a long cycle potential.

Polymer micelles mainly using copolymers can obtain various physical properties by changing the type and composition ratio of monomers, and in general, the physical stability and the dynamic equilibrium constant provide advantages over low molecular micelles.

Therefore, by applying various monomers and copolymers prepared by adjusting the ratio thereof, it is possible to enhance the solubilization of poorly soluble drugs and to improve the stability and efficiency of the conventional micelles, as described above. By applying the polymer micelle with the present invention, it can be used as an additive material having a sensitivity to external stimuli, as well as a hydrophobic drug and a carrier for gene delivery.

In the method of forming nanoparticles using a complex reaction of the ionic polymer, the cationic polymer may aggregate DNA at 50 to 200 nm as a non-viral gene carrier. This is to cause the aggregation of the DNA through the electrostatic interaction of the phosphate anion and the NON-virus vector cation of the DNA.

At this time, the ionic strength of the medium and the cation strength of the corresponding ion cause DNA aggregation. In DNA aggregation, polyvalent cations cause coulomb attraction to prevail over entropic attraction in constant mixing so that the DNA aggregates into spherical, toroid or rod-like. In this case, the size of the DNA aggregate depends on the topology and cationic properties of the DNA, and generally forms nanoparticles of 200 nm or less.

About 400 to 500 base pairs are involved in the formation of the DNA aggregate, and the aggregation between the cation and the DNA is mainly due to the change of free energy through electrostatic neutralization, but the steric and chemical changes such as bending, hydration, mixing, etc. The same factor also plays an important role in DNA aggregation.

In the method of forming nanoparticles using the complex reaction of the ionic polymer, the nanoparticles may utilize a method of binding to a surface during endosomal escape (for example, gene transfer) for high expression to give a temperature stimulus. After manufacturing the lens according to the relevant part, it is combined with pluronic (poly (ethylene oxide) [PEO] -poly (propylene oxide) [PPO]-[PEO])) on the surface shock) can cause endosomes to escape. In addition, due to the fluoric nanoparticles are produced by the transition to the surface of the resulting lens, the stimulation at a low temperature to induce bonding.

On the other hand, the drug carrier in the present invention, Bromo-deoxyuridine, F-Fluoro-uraci, Lododeoxyuridir, Dopamine nor-epinephrine, Retinoic acid, Paclitaxel, Substance P, Carmustine, Hormone agonist, Carboplatin, Isoniazid, Estradiol, Dopamine, Levodopa, It is possible to deliver any one or more drugs selected from Adenosine, Timolol maleate, Bunazosin, Levobunolol HCl, Betaxolol HCl, Dorzolamide hydrochloride, Brinzolamide, Acetazolamide, Methazolamide, Latanoprost, Travoprost, Bimatoprost, Tafluprost, Isopropyl unoprostone, Brimonidine and Pilocarpine.

In addition to the drug delivery polymers listed above, it is of course possible to apply a variety of known drug delivery polymers according to the type of treatment target or disease.

Table 1 shows the action of the drug delivery polymers.

Drug delivery polymer Observed activity Action Bromo-deoxyuridine in-vivo cell label Cortical wound level F-Fluoro-uraci in vitro release 21 days release Iododeoxyuridir in vitro release 7-35 day release Dopamine nor-epinephrine Parkinson rat model Rotational behavior for 8 weeks
decrease Retinoic acid vitreoretinpathy model
in-vivo treatment 40 days of release and
Reduced retinal detachment Paclitaxel in vitro release
in-vivo iv release Than 60 days release direct injection
High organizational level Substance P Promoting Toxicity rat model Striatal after QA administration
Dopaminergic Nerve Loss Reduction Carmustine Release into brain parenchyma After longitudinal direct injection
Increased drug survival Hormone agonist subcutaneous release in vivo 20-50 day release Carboplatin in vitro release
in vivo brain release Release for 22 days,
Lincar release for 30 days Isoniazid in vitro release 49 day release Estradiol in vitro release 40-60 day release Dopamine in vitro release 15-30 day release Levodopa in vitro release 2-year release Adenosine Tickling rat model Reduced spasm for two weeks Timolol maleate Of glaucoma disease
Waterproof produce degradation Sympathetic suppression Bunazosin Levobunolol HCl Betaxolol HCl Dorzolamide hydrochloride Carbonic anhydrase Inhibition Brinzolamide Acetazolamide Methazolamide Latanoprost Of glaucoma disease
Waterproof spill increase Lowering intraocular pressure Travoprost Bimatoprost Tafluprost Isopropyl unoprostone Brimonidine Sympathetic excitement Pilocarpine Parasympathetic operation

The drug delivery polymer as described above improves the mechanical, thermodynamic, and biological properties, and in particular, the microsperes of PLA (polylactic acid) and PLGA (polylactic-glycolic acid) improve biocompatibility and maintain the sustained release of drug. As an excellent agent, it has been used in small molecule therapeutic drugs such as cisplatin, prostaglandin E2, progesterone, mitomycin C, and proteins such as human bone morphogenesis proteins, beta-lactoglobulin, neurotransmitter, and recently plasmid proteins, but this delivery system Is best suited for delivery of therapeutic proteins. The reason why protein drugs are added to these drug delivery polymers and used in drug delivery systems (DDS) is that

1) Protein drug shows high efficacy even in small doses,

2) The absorption and biocompatibility of oral administration due to the large molecular weight is low and decomposes quickly in the GI environment.

3) It has a short half-life in body fluids due to its easy chemical decomposition with peptidases.

4) pharmacological action peculiar to protein drugs that require a small amount of drugs continuously for a long time,

5) It can withstand physical stress during the encapsulation process, ie mechanical consumption, exposure to organic solvents and temperature changes.

The present invention consequently improves the drug loading ability of soft contact lenses, allowing them to combat inflammatory eye conditions, dry eye and individuals in need of combat.

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples.

EXAMPLE

Preparation of the soft contact lens for drug delivery according to the present invention was carried out by the following method.

To prepare a low-resin resin composition, 100% stock of 2-hydroxyethyl methacrylate raw material was purified to 99% content of the entire polymerization solution, and the required composition and the drug carrier, Bromo-deoxyuridine, F -Fluoro-uraci, Lododeoxyuridir, Dopamine nor-epinephrine, Retinoic acid, Paclitaxel, Substance P, Carmustine, Hormone agonist, Carboplatin, Isoniazid, Estradiol, Dopamine, Levodopa and Adenosine were added sequentially and mixed to prepare a low-content resin composition. .

The low-resin resin composition prepared was ground to a nanoparticle size of 500 nm, and the ground nanoparticles were added and polymerized to the high-function contact lens composition.

Meanwhile, in the polymerization, radical polymerization was carried out using azobisisobutyronitrile (AIBN), which is a radical initiator, and the mixed solution was added to a contact lens mold using a bulk polymerization method without using a solvent, and then in an oven at 100 ° C. or lower. After the polymerization for 5 hours, a molded article was prepared by removing a lens having a thickness of about 1 mm from the center portion of the mold plate.

Experimental Example 1 Antibacterial Test (Solid medium test)

To verify the ability of the antimicrobial drug soft contact lens transfer according to the present invention, Staphylococcus aureus (SA: staphylococcus aureus), and Escherichia coli (E. coli: eschericchia coli ) was used for antimicrobial testing. The strains were each collected 1 ml of the solution diluted in 5 ml of distilled water, and diluted repeatedly three times in the same manner as described above.

As a control, commercially available soft contact lenses (manufactured by A company and B company) were used. In the experimental group, a soft contact lens containing the drug carrier prepared in Example was used. Both control and experimental groups were sterilized using powdered samples (0.2 g each) obtained through drying and grinding, and 1 ml of two bacterial suspensions were added to the liquid Nutrient Agar medium cooled to 40 to 45 ° C. Incubated for 24 hours in an incubator maintained at ℃, CFU (colony forming unit) of the strains formed on the solid medium was measured.

The experimental results, when compared to the commercially available contact lenses (A, B, Inc.) that is, the soft contact lens according to the embodiment of the present invention is at least about 80 to 90% for E. coli (E. coli) and SA (Staphylococcus aureus) The strains were confirmed to have died. This suggests that the soft contact lens into which the drug carrier is introduced exhibits superior antimicrobial activity than the soft contact lenses of other controls. That is, by adding and polymerizing the drug carrier to the contact lens, it can be seen that the cationic functional groups present on the surface contribute to the expression of excellent antimicrobial properties.

Experimental Example 2 Cytotoxicity Test

In order to determine the biocompatibility of the soft contact lens for drug delivery according to the present invention, an experiment for evaluating cytotoxicity was performed. Cytotoxicity (in vitro) as part of the biological stability test corresponds to the stage of cell and tissue damage from denaturation (reversible) to necrosis (non-reversible), and eluates of biomaterials using cell culture technology (experimental) It is an experiment to evaluate the effect on the cell lysis or growth inhibition and other cells by the liquid).

First, put the soft contact lens of the present invention in a PBS (phosphate buffer saline) solution, and maintained for 24 hours to make an exuding solution (drug delivery material), and then divided into a control group (medium + PBS solution) and two experimental groups Experiment.

In each group, mouse fibroblast L929 cell line cells were seeded at a concentration of 1 × 10 ⁵ / well and incubated in an incubator maintained at 37 ° C. and 5% CO ₂ for 24 hours. After addition and incubation for an additional 48 hours, cell adhesion and cell viability were examined. Prior to testing, each SAMPLE was placed in 70% ethanol and sterilized under UV (254 nm) for 24 hours and washed 3-4 times with PBS solution. Its absorbance was measured by ELISA (SpectraMax M5, Molecular Devices, Arlington, USA).

As a result of the experiment, compared to the control (Control), showed a survival rate of more than 90% in all samples. Through this, the soft contact lens of the present invention prepared according to each ratio can be confirmed that there is no cytotoxicity, which means that it is biocompatible.

Claims (8)

The drug carrier is added to the low-functional resin composition, which is the raw material of the lens, and polymerized to form a low-performance resin composition of a solid substrate. The low-functional resin composition of the solid substrate is a colloid having a surface area of 1-900 nm. It is pulverized into nanoparticles, which are non-uniform dispersed particles in the phase, and the pulverized nanoparticles are added to the high-function contact lens composition and polymerized. A method for producing a soft contact lens for drug delivery, characterized in that it is produced by a lens.
According to claim 1,
The contact lens forms a color pattern by printing and spraying a binder composition on a desired print target area,
The binder composition may include a pigment, a drug carrier and an oily solvent-based polyurethane, a polyacryl, a urethane acrylate-based or an aqueous solvent-based polyurethane, and a polyacryl. , The method of manufacturing a soft contact lens for drug delivery, characterized in that the binder composition consisting of any one or a mixture of two or more of the urethane acrylate (urethane acrylate) series. According to claim 1,
The drug carrier,
After dissolving the polymer in an organic solvent that can dissolve the polymer,
By dispersing the solution in which the polymer is dissolved in an aqueous solution to which the emulsifier is added, the emulsifier and polymer are coacervation and solidification reaction to form spherical nanoparticles. Method for manufacturing a contact lens. According to claim 1,
The drug carrier,
A method for producing a soft contact lens for drug delivery, comprising an amphiphilic block copolymer polymer having hydrophilicity and hydrophobicity. According to claim 1,
The drug carrier,
A method for producing a soft contact lens for drug delivery, characterized in that it is a cationic polymer in which DNA, which is a non-viral gene carrier, is aggregated in a size of 50-200 nm. The method according to any one of claims 1 to 5,
The drug carrier,
Bromo-deoxyuridine, F-Fluoro-uraci, Lododeoxyuridir, Dopamine nor-epinephrine, Retinoic acid, Paclitaxel, Substance P, Carmustine, Hormone agonist, Carboplatin, Isoniazid, Estradiol, Dopamine, Levodopa, Adenosine, Timolol maleate, Bunbunolin Bunbunos Method for producing a soft contact lens for drug delivery, characterized in that it comprises any one or more drug delivery polymer selected from betaxolol HCl, Dorzolamide hydrochloride, Brinzolamide, Acetazolamide, Methazolamide, Latanoprost, Travoprost, Bimatoprost, Tafluprost, Isopropyl unoprostone, Brimonidine and Pilocarpine . The method according to any one of claims 1 to 5,
The drug delivery method, the drug delivery method of manufacturing a soft contact lens for drug delivery, characterized in that for delivering the drug by the mechanism of the drug delivery system (DDS, drug delivery system). According to claim 1,
The polymerization is a drug, characterized in that by filtering the resin composition to which the drug carrier is added, by introducing a bulk polymerization method and radically polymerizing the resin composition filtered in the contact lens mold at a temperature of 60-100 ℃ for 15-300 minutes. Method for manufacturing a soft contact lens for transmission.

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