KR102584849B1 - Antioxidant and antiviral contact lens - Google Patents

Abstract

The present invention relates to a contact lens that can stably store antioxidant and antiviral substances when stored and effectively release antioxidant and antiviral substances into the cornea when worn on the user's eyes.

Description

Antioxidant and antiviral contact lenses {ANTIOXIDANT AND ANTIVIRAL CONTACT LENS}

The present invention relates to antioxidant and antiviral contact lenses.

Contact lenses are used around the world for vision correction and cosmetic purposes. As the contact lens market continues to grow, the number of contact lens wearers worldwide reached 125 million in 2016, and the use of contact lenses is becoming increasingly important. Recently, contact lenses that can protect the eyes from oxidative stress and contact lenses that can minimize ocular side effects due to viral infections have been developed.

Ultraviolet rays increase oxidative stress, causing the tear layer on the surface of the cornea to evaporate. A substance called lactoferrin contained in the tear layer is known to have an antioxidant effect, but as it disappears, the antioxidant power of the eyes decreases accordingly. Various methods, such as consuming functional foods and directly instilling eye drops, have been attempted to reduce oxidative stress through antioxidant substances, but it is difficult to demonstrate a direct antioxidant effect in the eyes.

The use of contact lenses is widely known as a risk factor for keratoconjunctivitis, and interest in viral infections is increasing due to the 'COVID-19 pandemic' that occurred in 2020. COVID-19 (SARS-CoV-2) is assumed to use 'angiotensin-converting enzyme 2' (ACE2) and other accessory proteins for cell entry, in 0.8% of SARS-CoV-2 patients. Conjunctival injection has been reported, and some studies speculate that SARS-CoV-2 may be transmitted through the conjunctiva.

Therefore, the use of contact lenses with antiviral activity can be considered as one of the measures against viral infection, as it can be expected to play a protective role in the conjunctiva against 'SARS-CoV-2', a type of coronavirus.

Meanwhile, many studies are being conducted to develop antibiotics for treatment by inserting them into soft lenses, but development is currently limited to substances used as medicines. In addition, soft lenses are stored in a buffer solution after manufacturing. If ingredients with antioxidant and antiviral properties are not released from the lens during distribution and storage and are released at the corneal temperature after wearing, maximum antioxidant and antiviral properties can be expected.

Therefore, there is a need to develop a 'corneal temperature-sensitive antioxidant and antiviral contact lens' that releases drugs in response to the cornea's temperature of 35°C.

The present invention provides a contact lens that can stably store antioxidant and antiviral substances when stored and effectively release antioxidant and antiviral substances into the cornea when worn on the user's eyes.

However, the problem to be solved by the present invention is not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

One embodiment of the present invention is a polymerization solution containing a polar functional group-containing (meth)acrylate-based monomer, an alkyl group-containing (meth)acrylate-based monomer, a crosslinker, a temperature-sensitive compound containing a polyether diol, and an initiator. A polymer matrix comprising a polymer of; and a flavonoid compound loaded into the polymer matrix and containing rutin.

Antioxidant and antiviral contact lenses according to an embodiment of the present invention can effectively implement antioxidant and antiviral multi-actions.

In addition, the antioxidant and antiviral contact lens according to an embodiment of the present invention can effectively release antioxidant and antiviral substances when worn on the user's eyes.

However, the effects of the present invention are not limited to the effects described above, and may be expanded in various ways without departing from the spirit and scope of the present invention.

Figure 1 shows the results of evaluating the amount of rutin loaded into the contact lenses manufactured in Reference Examples 1 to 4 of the present invention.
Figures 2 and 3 show the results of evaluating the amount of rutin released from the contact lenses manufactured in Reference Examples 1 to 4 of the present invention.
Figures 4 and 5 show the results of evaluating the amount of rutin released from the contact lenses manufactured in Reference Examples 4 to 9 of the present invention.
Figures 6 and 7 show the results of evaluating the amount of rutin released from the contact lenses manufactured in Examples 1, 2, and Comparative Example 1 of the present invention.
Figure 8 shows the results of evaluating the antioxidant activity of contact lenses prepared in Examples 2 and 3 of the present invention.

Throughout the specification of the present application, when a part is said to “include” a certain element, this means that it may further include other elements rather than excluding other elements, unless specifically stated to the contrary.

Throughout this specification, when a member is said to be located “on” another member, this includes not only the case where the member is in contact with the other member, but also the case where another member exists between the two members.

Throughout the specification herein, the unit “part by weight” may refer to the ratio of weight between each component.

Throughout this specification, “(meth)acrylate” is used to collectively refer to acrylates and methacrylates.

Hereinafter, the present invention will be described in more detail.

One embodiment of the present invention is a polymerization solution containing a polar functional group-containing (meth)acrylate-based monomer, an alkyl group-containing (meth)acrylate-based monomer, a crosslinker, a temperature-sensitive compound containing a polyether diol, and an initiator. A polymer matrix comprising a polymer of; and a flavonoid compound loaded into the polymer matrix and containing rutin.

Antioxidant and antiviral contact lenses according to an embodiment of the present invention can effectively implement antioxidant and antiviral multi-actions.

In addition, the antioxidant and antiviral contact lens according to an embodiment of the present invention can effectively release antioxidant and antiviral substances when worn on the user's eyes.

According to one embodiment of the present invention, the antioxidant and antiviral contact lens may include a polymer matrix that is the basis of the contact lens. That is, the polymer matrix can be formed in the form of a contact lens. The flavonoid compound containing rutin can be loaded into a polymer matrix formed in the form of a contact lens.

The polymerization solution may be polymerized to form the polymer matrix. For example, the polymer matrix can be formed by thermally polymerizing, photopolymerizing, or drying the polymerization solution. At this time, in terms of production time and production efficiency of the polymer matrix, it may be desirable to form the polymer matrix by thermally polymerizing the polymerization solution.

According to an exemplary embodiment of the present invention, the polymerization solution may include a (meth)acrylate-based monomer containing a polar functional group as a monomer for forming the polymer matrix. Specifically, the polar functional group-containing (meth)acrylate-based monomer may contain a hydroxy group. That is, the polar functional group-containing (meth)acrylate-based monomer may contain a hydroxy group as a polar functional group. When the polar functional group-containing (meth)acrylate-based monomer containing a hydroxy group is used, the polymer matrix can be effectively loaded with the flavonoid compound containing the rutin. Specifically, as described later, the flavonoid compound containing the rutin contains a plurality of polar functional groups (e.g., hydroxy group, ether group) in the molecule, and the polar functional group-containing (meth)acrylate containing the hydroxy group By using a monomer, the flavonoid compound containing the rutin can be more easily loaded. In addition, the polar functional group-containing (meth)acrylate-based monomer has excellent compatibility with the cross-linking agent and the temperature-sensitive compound, making it possible to produce contact lenses of higher quality.

Meanwhile, the polar functional group-containing (meth)acrylate-based monomer may include a carboxyl group, amide group, or amine group as a polar functional group. However, when the polar functional group-containing (meth)acrylate-based monomer contains a polar functional group other than a hydroxy group, a problem may occur in which the loading and release properties of the flavonoid compound containing rutin of the contact lens are deteriorated. That is, the polar functional group-containing (meth)acrylate-based monomer containing a hydroxy group as a polar functional group may be a monomer optimized for the loading and release of the flavonoid compound including rutin.

According to one embodiment of the present invention, the polar functional group-containing (meth)acrylate-based monomer may contain alkylene having 4 or less carbon atoms. Specifically, the polar functional group-containing (meth)acrylate-based compounds include hydroxymethyl (meth)acrylate, hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, and hydroxybutyl (meth)acrylate. It may include at least one of the rates. A (meth)acrylate-based compound containing a polar functional group having an alkylene having 4 or less carbon atoms has excellent compatibility with the cross-linking agent and the temperature-sensitive compound, and more effectively loads the flavonoid compound containing the rutin into the polymer matrix. You can do it. In particular, as the polar functional group-containing (meth)acrylate-based monomer, 2-hydroxyethyl methacrylate can be used.

According to one embodiment of the present invention, the content of the polar functional group-containing (meth)acrylate-based monomer may be 85 parts by weight or more and 98.5 parts by weight or less based on 100 parts by weight of the polymerization solution. Specifically, based on 100 parts by weight of the polymerization solution, the content of the polar functional group-containing (meth)acrylate monomer is 87.5 parts by weight to 98.5 parts by weight, 88 to 98.5 parts by weight, and 85 to 95 parts by weight. It may be less than or equal to 90 parts by weight and less than or equal to 98.5 parts by weight. When the content of the polar functional group-containing (meth)acrylate monomer contained in the polymerization solution is within the above-mentioned range, the flavonoid compound containing the rutin and vitamin E can be effectively loaded into the polymer matrix, which will be described later. As shown, flavonoid compounds containing rutin can be effectively released at a temperature of about 34°C or more and 36°C or less, which corresponds to the human cornea temperature. In addition, the polymer matrix can easily achieve physical properties suitable for use as contact lenses (for example, moisture content of 35% to 40%).

According to an exemplary embodiment of the present invention, the polymerization solution may include an alkyl group-containing (meth)acrylate-based monomer as a monomer for forming the polymer matrix. Specifically, the alkyl group-containing (meth)acrylate-based monomer may contain an alkyl group having 1 to 4 carbon atoms. More specifically, the alkyl group-containing (meth)acrylate-based monomer may include at least one of methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, and butyl (meth)acrylate. there is. In particular, methyl acrylate can be used as the alkyl group-containing (meth)acrylate monomer. By using the above-described types of alkyl group-containing (meth)acrylate-based monomers, a polymer matrix having physical properties suitable for use as a contact lens can be implemented.

According to one embodiment of the present invention, the content of the alkyl group-containing (meth)acrylate-based monomer may be 0.5 parts by weight or more and 1.0 parts by weight or less based on 100 parts by weight of the polymerization solution. Specifically, based on 100 parts by weight of the polymerization solution, the content of the alkyl group-containing (meth)acrylate monomer may be 0.6 parts by weight or more and 0.8 parts by weight or less, or 0.5 parts by weight or more and 0.7 parts by weight or less. When the content of the alkyl group-containing (meth)acrylate monomer contained in the polymerization solution is within the above-mentioned range, the polymer matrix has physical properties suitable for use as a contact lens (for example, a moisture content of 35% to 40%) ) can be easily implemented.

According to one embodiment of the present invention, the polymerization solution may include a cross-linking agent. The cross-linking agent may include two or more (meth)acrylate groups. Specifically, the cross-linking agent may include 2 or more and 4 or less, or 2 or more and 3 or less (meth)acrylate groups. For example, the cross-linking agent may include at least one of ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, and trimethylolpropane tri(meth)acrylate. The crosslinking agent containing two or more (meth)acrylate groups is compatible with temperature-sensitive compounds including the polar functional group-containing (meth)acrylate monomer, alkyl group-containing (meth)acrylate monomer, and polyether diol. This is excellent, and a polymer matrix can be formed more stably.

According to an exemplary embodiment of the present invention, the content of the cross-linking agent may be 0.5 parts by weight or more and 1.0 parts by weight or less based on 100 parts by weight of the polymerization solution. Specifically, based on 100 parts by weight of the polymerization solution, the content of the crosslinking agent may be 0.6 parts by weight or more and 0.8 parts by weight or less, or 0.5 parts by weight or more and 0.7 parts by weight or less. When the content of the cross-linking agent contained in the polymerization solution is within the above-mentioned range, the polymer matrix can be stably formed, and the flavonoid compound including rutin can be more effectively loaded into the polymer matrix. In addition, the polymer matrix can easily achieve physical properties suitable for use as contact lenses (for example, moisture content of 35% to 40%).

According to an exemplary embodiment of the present invention, the polymerization solution may include the temperature-sensitive compound. The temperature-sensitive compound is included in the polymer matrix, and the temperature-sensitive compound shrinks at a temperature higher than the corneal temperature (e.g., about 34°C or more and 36°C or less) and swells at a temperature lower than the corneal temperature. It may be a compound that shows this pattern. Additionally, the change in aspect of the temperature-sensitive compound may be reversible depending on temperature. By using a temperature-sensitive compound having the physical properties described above, when the contact lens is stored at a temperature lower than the corneal temperature, flavonoid compounds including rutin, an antioxidant and antiviral substance, can be stably stored in the contact lens, When the contact lens is worn on the user's eye and reaches a temperature higher than the corneal temperature, the flavonoid compound containing the rutin can be effectively delivered to the user's cornea. Through this, the antioxidant and antiviral contact lens can effectively release antioxidant and antiviral substances when worn on the user's eyes, effectively implementing antioxidant and antiviral multi-action.

According to one embodiment of the present invention, the temperature-sensitive compound may be a polyether-based diol containing a polyether-based main chain and hydroxy groups bonded to both ends of the main chain. The temperature-sensitive compound containing a polyether-based diol may have excellent compatibility with the polar functional group-containing (meth)acrylate-based monomer and the cross-linking agent, and contact lenses of the flavonoid compound containing the rutin depending on temperature Storage and release can be effectively controlled. For example, the temperature-sensitive compound may include a compound represented by Formula 1 below.

[Formula 1]

In one embodiment of the present invention, Pluronic F127, a compound represented by Formula 1, can be used as the temperature-sensitive compound. The temperature-sensitive compound contains a plurality of ether bonds in the main chain of the molecular structure, and hydroxy groups are bonded to both ends, and thus the polar functional group-containing (meth)acrylate monomer containing the hydroxy group and a plurality of hydroxy groups. It may have excellent compatibility with the flavonoid compound containing rutin, and can effectively suppress a decrease in the loading amount of the flavonoid compound containing rutin in the polymer matrix.

According to one embodiment of the present invention, the concentration of the temperature-sensitive compound may be 5 w/v% or more and 10 w/v% or less. That is, the temperature-sensitive compound may be mixed in the polymerization solution in the form of a solution. To prepare the temperature-sensitive compound solution, the temperature-sensitive compound and a solvent can be mixed, and distilled water can be used as the solvent.

According to one embodiment of the present invention, the content of the temperature-sensitive compound may be 3.5 parts by weight or more and 12.5 parts by weight or less based on 100 parts by weight of the polymerization solution. Specifically, based on 100 parts by weight of the polymerization solution, the content of the temperature-sensitive compound may be 5 parts by weight or more and 10 parts by weight or less, 3.5 parts by weight or more and 10 parts by weight or less, or 5 parts by weight or more and 12.5 parts by weight or less. When the content of the temperature-sensitive compound contained in the polymerization solution is within the above-mentioned range, the contact lens can stably store the flavonoid compound containing the rutin at a temperature lower than the corneal temperature, and at a temperature higher than the corneal temperature. Flavonoid compounds containing the rutin can be effectively released.

According to one embodiment of the present invention, the weight ratio of the temperature-sensitive compound and the polar functional group-containing (meth)acrylate-based monomer contained in the polymerizable solution may be 1:5 to 1:20. Specifically, the weight ratio of the temperature-sensitive compound and the polar functional group-containing (meth)acrylate monomer contained in the polymerizable solution is 1:7.5 to 1:19, 1:8.5 to 1:19, and 1:5 to 1. :12.5, or 1:10 to 1:20.

When the weight ratio of the temperature-sensitive compound and the polar functional group-containing (meth)acrylate-based monomer contained in the polymerizable solution is within the above-mentioned range, the flavonoid compound containing the rutin can be effectively loaded into the contact lens, The contact lens can stably store the flavonoid compound containing rutin at a temperature lower than the corneal temperature, and can effectively release the flavonoid compound containing the rutin at a temperature higher than the corneal temperature.

According to one embodiment of the present invention, the weight ratio of the cross-linking agent and the temperature-sensitive compound contained in the polymerizable solution may be 1:5 to 1:15. Specifically, the weight ratio of the cross-linking agent and the temperature-sensitive compound contained in the polymerizable solution may be 1:6 to 1:13, 1:5 to 1:8, or 1:10 to 1:15. When the weight ratio of the cross-linking agent and the temperature-sensitive compound contained in the polymerizable solution is within the above-mentioned range, the temperature-sensitive compound can be more homogeneously provided in the polymer matrix, and through this, the contact lens can operate at a temperature higher than the corneal temperature. At low temperatures, the flavonoid compounds containing rutin can be stably stored, and at temperatures higher than the corneal temperature, the flavonoid compounds containing rutin can be effectively released.

According to one embodiment of the present invention, the initiator may be a photoinitiator or a thermal initiator. Depending on the method of polymerizing the polymerization solution, the type of the initiator can be selected, and any initiator used in the art can be used without limitation. For example, the initiator may be azodiisobutyronitrile (AIBN), benzoin methyl ether (BME), 2,5-dimethyl-2,5-di-(2-ethylhexanoylperoxy)hexane, dimethyl It may include at least one of doxyphenyl acetophenone (DMPA) and 2,2-dimethoxy-2-phenylacetopenone (2,2-Dimethoxy-2-Phenylacetopenone, DMPAP). However, the type of initiator is not limited.

According to one embodiment of the present invention, the content of the initiator may be 0.3 parts by weight or more and 0.7 parts by weight or less, based on 100 parts by weight of the polymerization solution. When the content of the initiator contained in the polymerization solution is within the above-mentioned range, the polymer matrix can be stably formed from the polymerization solution.

According to one embodiment of the present invention, the antioxidant and antiviral contact lens may include a flavonoid compound including the rutin loaded into the polymer matrix. Specifically, the flavonoid compound may include at least rutin, and more specifically, the flavonoid compound may be rutin. By containing rutin, a natural substance, the contact lenses can implement multi-actions of antioxidant and antiviral properties. The rutin may be a compound represented by the following formula (2).

[Formula 2]

Rutin corresponds to a glycoside in which ‘rutinose (a disaccharide consisting of glucose and rhamnose)’ is bound to carbon 3 of quercetin. That is, the contact lens may contain rutin in the form of a glycoside.

According to one embodiment of the present invention, the concentration of the flavonoid compound loaded into the polymer matrix may be 50 μM or more and 200 μM or less. That is, the flavonoid compound containing the rutin can be loaded into the polymer matrix in the form of a solution. Specifically, the concentration of the rutin loaded into the polymer matrix may be 50 μM or more and 200 μM or less, 100 μM or more and 200 μM or less, 150 μM or more and 200 μM or less, or 200 μM. When the concentration of the rutin to be loaded into the polymer matrix is within the above-mentioned range, the rutin can be effectively loaded into the polymer matrix, and the contact lens can effectively release the rutin when worn on the user's eyes.

According to one embodiment of the present invention, the concentration of the flavonoid compound loaded into the polymer matrix may be 10 μM or more and 40 μM or less. That is, the concentration of rutin contained in the contact lens after loading into the polymer matrix may be 10 μM or more and 40 μM or less. When the concentration of rutin contained in the contact lens is within the above-mentioned range, the contact lens can effectively implement the multi-action of antioxidant and antiviral.

According to one embodiment of the present invention, the antioxidant and antiviral contact lens may further include vitamin E loaded into the polymer matrix. Vitamin E is a hydrophobic material that can be loaded into the contact lens and act as a barrier to prevent rapid release of the flavonoid compound. That is, by loading vitamin E into the polymer matrix, it prevents a large amount of rutin from being released in a short period of time when the contact lens is worn on the user's eyes, and delays the release time of rutin to enhance the antioxidant and antiviral effects. It can be maintained for a long time.

According to one embodiment of the present invention, the concentration of vitamin E loaded into the polymer matrix may be 0.2 w/v% or more and 1.0 w/v% or less. Specifically, the concentration of vitamin E to be loaded into the polymer matrix is 0.2 w/v% or more and 0.8 w/v% or less, 0.2 w/v% or more and 0.6 w/v% or less, and 0.2 w/v% or more and 0.4 w/v. % or less, or 0.2 w/v%. When the concentration of vitamin E to be loaded into the polymer matrix is within the above-mentioned range, the release time of rutin can be effectively delayed, and the antioxidant and antiviral effects can be maintained for a longer period of time. Meanwhile, if the concentration of vitamin E exceeds 1.0 w/v%, the problem of clouding of the surface of the contact lens may occur.

According to one embodiment of the present invention, the polymerization solution may be polymerized to form a polymer matrix in the form of a contact lens, and the polymer matrix may be loaded by immersing it in a flavonoid compound containing rutin. In other words, the contact lens is loaded in a physical manner by immersing it in the rutin solution, which allows the contact lens to expand and contain the rutin solution inside. Afterwards, the contact lenses loaded with routine can be dried. Similarly to the above, in order to load vitamin E, contact lenses can be loaded by immersing them in a vitamin E solution and then dried.

Hereinafter, the present invention will be described in detail with reference to examples. However, the embodiments according to the present invention may be modified into various other forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. The embodiments of this specification are provided to more completely explain the present invention to those skilled in the art.

Example

ingredient

2-hydroxyethyl methacrylate (HEMA), a (meth)acrylate-based monomer containing a polar functional group, was purchased from Lotte chemical, Korea. Methyl acrylate (MA), an alkyl group-containing (meth)acrylate monomer, ethylene glycol dimethacrylate (EGDMA), a cross-linking agent, and Pluronic, a temperature-sensitive compound represented by Formula 1 above. F-127, azobisisobutyronitrile (AIBN) as a thermal initiator, 2,2-Dimethoxy-2-Phenylacetopenone (DMPAP) as a photoinitiator, and rutin were purchased from Sigma-Aldrich, USA. DPPH (1,1-diphenyl-2-picryl hydrazyl) was purchased from Santa Cruz Biotechnology, CA, USA.

Reference Example 1 to Reference Example 4

2-Hydroxyethyl methacrylate (HEMA), methyl acrylate (MA), ethylene glycol dimethacrylate (EGDMA), and AIBN were placed in a 10 ml vial and stirred with a magnetic bar for 10 minutes to prepare a polymerization solution. At this time, based on 100 parts by weight of the polymerization solution, the content of HEMA was adjusted to 98.1 parts by weight, the content of MA was adjusted to 0.6 parts by weight, the content of EGDMA was adjusted to 0.8 parts by weight, and the content of AIBN was adjusted to 0.5 parts by weight. This is to manufacture contact lenses with a moisture content of 38%.

Afterwards, 78 μl of the stirred polymerization solution was equally injected into a mold for soft contact lenses (Plano, BC 8.6, DIA 14.2), and heated in an oven (Wise oven, DAIHAN scientific, Korea) at a temperature of 120°C for 50 minutes. polymerized. After polymerization, the contact lenses were hydrated in PBS (pH 7.4) for 24 hours. After the hydration process was completed, the lenses were dried at room temperature for 24 hours.

After preparing a stock solution with a rutin concentration of 200 μM, rutin solutions with different concentrations of 50 μM, 100 μM, 150 μM, and 200 μM were prepared. Rutin solutions of different concentrations were placed in 10 ml vials, 1.5 ml each, and one dried soft contact lens was placed in each vial and loaded for 24 hours while blocking light. After loading the soft contact lenses, the rutin solution on the front and back of the lenses was washed with 1.5 ml of PBS and dried for 24 hours at room temperature, blocking light.

Reference Example 1 used a rutin solution with a concentration of 50 μM for loading, Reference Example 2 used a rutin solution with a concentration of 100 μM for loading, Reference Example 3 used a rutin solution with a concentration of 150 μM for loading, and Reference Example 4 used a rutin solution with a concentration of 200 μM. A routine solution of similar concentration was used for loading.

Solution for polymerization (parts by weight) Rutin solution concentration (μM) HEMA M.A. EGDMA AIBN Reference example 1 98.1 0.6 0.8 0.5 50 Reference example 2 98.1 0.6 0.8 0.5 100 Reference example 3 98.1 0.6 0.8 0.5 150 Reference example 4 98.1 0.6 0.8 0.5 200

Reference Example 5 to Reference Example 9

Add 0.2g, 0.4g, 0.6g, 0.8g, and 1.0g of vitamin E to 10 ml of ethanol, vortex for 20 seconds, and mix with a magnetic bar for 5 minutes to obtain 0.2 w/v%, 0.4 w/v%. , prepared at concentrations of 0.6 w/v%, 0.8 w/v%, and 1.0 w/v%. 1.5 ml of the prepared vitamin E solution of each concentration was added to each 10 ml vial, and one contact lens not loaded with rutin prepared in Reference Example 1 was added to each vial to load vitamin E for 24 hours. After loading the contact lenses with vitamin E, the vitamin E on the surface was washed with ethanol and distilled water in that order and dried at room temperature for 24 hours. The dried vitamin E-loaded contact lenses were each soaked in 1.5 ml of 200 μM rutin solution for 24 hours. After loading, each contact lens was washed with 1.5 ml of PBS and dried at room temperature, blocking light, for 24 hours.

Reference Example 5 used a vitamin E solution with a concentration of 0.2 w/v% for loading, Reference Example 6 used a vitamin E solution with a concentration of 0.4 w/v% for loading, and Reference Example 7 used a vitamin E solution with a concentration of 0.6 w/v%. A vitamin E solution of was used for loading, Reference Example 8 used a vitamin E solution with a concentration of 0.8 w/v% for loading, and Reference Example 9 used a vitamin E solution with a concentration of 1.0 w/v% for loading.

Solution for polymerization (parts by weight) Rutin solution concentration (μM) Vitamin E
solution concentration
(w/v%) HEMA M.A. EGDMA AIBN Reference example 4 98.1 0.6 0.8 0.5 200 0 Reference example 5 98.1 0.6 0.8 0.5 200 0.2 Reference example 6 98.1 0.6 0.8 0.5 200 0.4 Reference example 7 98.1 0.6 0.8 0.5 200 0.6 Reference example 8 98.1 0.6 0.8 0.5 200 0.8 Reference example 9 98.1 0.6 0.8 0.5 200 1.0

Example 1

As a temperature-sensitive compound, 1 g of Pluronic F-127, a compound represented by Formula 1, was dissolved in 10 ml distilled water to prepare a 10 w/v% temperature-sensitive compound solution. Afterwards, 2-hydroxyethyl methacrylate (HEMA), methyl acrylate (MA), ethylene glycol dimethacrylate (EGDMA), DMPAP, and temperature-sensitive compound solution were placed in a 10 ml vial and stirred with a magnetic bar for 10 minutes to polymerize. A solution was prepared. At this time, based on 100 parts by weight of the polymerization solution, the content of HEMA is 93.1 parts by weight, the content of MA is 0.6 parts by weight, the content of EGDMA is 0.8 parts by weight, the content of DMPAP is 0.5 parts by weight, and the temperature-sensitive compound (solution) The content was adjusted to 5 parts by weight.

Inject 78 μl of the stirred polymerization solution into a mold for soft contact lenses (Plano, BC 8.6, DIA 14.2), block light, and use an ultraviolet lamp (VL-6-LM, Vilber Lourmat, France). By photopolymerizing at 365 nm, contact lenses were manufactured.

Thereafter, in the same manner as in Reference Example 4, rutin was loaded onto the contact lenses using a rutin solution with a concentration of 200 μM.

Example 2

In Example 1, the content of HEMA was adjusted to 88.1 parts by weight and the content of the temperature-sensitive compound (solution) was adjusted to 10 parts by weight, based on 100 parts by weight of the polymerization solution, as shown in Table 3 below. Rutin-loaded contact lenses were manufactured in the same manner as above.

Example 3

Contact lenses without rutin loading were manufactured in the same manner as in Example 2. Thereafter, in the same manner as Reference Example 5, a vitamin E solution with a concentration of 0.2 w/v% was loaded onto the contact lenses. Thereafter, in the same manner as in Reference Example 4, rutin was loaded onto the contact lenses using a rutin solution with a concentration of 200 μM.

Comparative Example 1

In Example 1, rutin-loaded contact lenses were manufactured in the same manner as Example 1, except that no temperature-sensitive compound was added when preparing the polymerization solution as shown in Table 2 below.

Solution for polymerization (parts by weight) Rutin solution concentration (μM) HEMA M.A. EGDMA AIBN Pluronic F-127 Comparative Example 1 98.1 0.6 0.8 0.5 0 200 Example 1 93.1 0.6 0.8 0.5 5 200 Example 2 88.1 0.6 0.8 0.5 10 200

Experiment example

Experimental Example 1

The amount of rutin loaded into the contact lenses of Reference Examples 1 to 4 was evaluated as follows.

The soft contact lenses that had been loaded in Reference Examples 1 to 4 were taken out, and the absorbance of the remaining rutin solution was measured. The concentration of the rutin solution remaining after loading was obtained using the formula derived from the calibration curve for each concentration of rutin. As shown in Equation 1 below, the concentration value of the remaining solution and the concentration value of the routine solution on the front and back of the lens were added and subtracted from the initial routine concentration value. This value was set as the amount of routine finally loaded into the lens.

[Equation 1]

Amount of rutin loaded = initial rutin solution concentration - (concentration of rutin solution remaining after loading + rutin solution concentration on front and back of lens)

Figure 1 shows the results of evaluating the amount of rutin loaded into the contact lenses manufactured in Reference Examples 1 to 4 of the present invention.

Referring to Figure 1, the amount of routine loaded into the contact lens (amount of routine included in the contact lens) calculated through Equation 1 above is 12.81 ± 0.44 μM for Reference Example 1 and 21.21 ± 0.98 for Reference Example 2. μM, Reference Example 3 was 26.71 ± 2.10 μM, and Reference Example 4 was 31.63 ± 3.42 μM. It was confirmed that as the concentration of the rutin solution used for loading increased, the amount of rutin loaded also increased.

Experimental Example 2

The physical properties of rutin released from the contact lenses of Reference Examples 1 to 4 were evaluated as follows.

1.5 ml of PBS (pH 7.4) was metered into each 10 ml vial. The contact lenses of Reference Examples 1 to 4 were placed in a vial containing 1.5 ml of quantified PBS, and the space between the vial lid and the gap between the vial was wrapped with parafilm to prevent evaporation. The release of rutin was carried out using a shaker (CR300, FINEPCR, Korea) at a speed of 50 rpm under the conditions of 35°C and 50% humidity, which are the same temperature conditions as the cornea. Excluding the initial release time, absorbance was measured every hour, and the contact lens was transferred to 1.5 ml of new PBS every time it was measured. Absorbance was measured using a microplate reader (Bio-TEK, IT/μQuant MQX200, 380 x 180 x 406mm) at the peak wavelength of 360nm. The amount of rutin released was calculated using a formula obtained through a calibration curve for each concentration of rutin over time.

Figures 2 and 3 show the results of evaluating the amount of rutin released from the contact lenses manufactured in Reference Examples 1 to 4 of the present invention.

Referring to Figure 2, the amount of release up to the first 30 minutes is 1.14 ± 0.23 μM for Reference Example 1, 3.22 ± 0.24 μM for Reference Example 2, 5.47 ± 0.25 μM for Reference Example 3, and 8.03 ± 0.83 μM for Reference Example 4. Contact lenses loaded with a higher concentration of rutin had a higher initial release amount. When the release rate was calculated using the slope of the graph, Reference Examples 1 to 4 were 2.4μM/h, 6.4μM/h, 10.9μM/h, and 16.1μM/h, respectively, and the contact lens of Reference Example 4 had the highest initial release rate. The release rate was shown.

Referring to Figure 3, when the release rate (%) was obtained through the data in Figure 2, the release rates up to the first 30 minutes were 8.89%, 15.16%, 20.48%, and 25.40% for Reference Examples 1 to 4, respectively, of the routine. Contact lenses loaded at higher concentrations also had higher initial release rates.

Referring to Figures 2 and 3, in Reference Example 1 and Reference Example 2, the release rate of rutin was on average 0 μM/h and 0.1 μM/h, respectively, between 2 and 4 hours after the rutin was released. Between 4 and 8 hours, the amount released increased to 5.11 ± 0.50 μM and 8.17 ± 1.11 μM, respectively. The cumulative release amount up to 24 hours was 5.11 ± 0.50 μM for Reference Example 1, 8.32 ± 1.36 μM for Reference Example 2, 15.16 ± 2.12 μM for Reference Example 3, and 19.57 ± 1.23 μM for Reference Example 4, indicating contacts loaded with a high concentration of rutin. The larger the lens, the higher the total emission amount. When this was expressed as a release rate (%), Reference Example 1 was 39.84%, Reference Example 2 was 39.21%, Reference Example 3 was 56.76%, and Reference Example 4 was 61.88%. The contact lens loaded with a higher concentration of rutin had a higher release rate. . That is, among lenses loaded with rutin at different concentrations, Reference Example 4 with a concentration of 200 μM had the best emission efficiency.

Experimental Example 3

For the contact lenses of Reference Examples 4 to 9, the amount of routine loaded was evaluated as follows.

In order to determine whether vitamin E, a hydrophobic substance, affects the loading amount of rutin, 200 μM was applied to the contact lenses of Reference Example 4, which was not loaded with vitamin E, and Reference Examples 5 to 9, which were loaded with different concentrations of vitamin E. The concentration of rutin solution was loaded. At this time, the amount of routine loaded into the contact lens was calculated using Equation 1 described above. The amount of loaded routine calculated through Equation 1 is 33.07±4.34μM for Reference Example 4, 28.54±1.42μM for Reference Example 5, 32.43±6.17μM for Reference Example 6, and 32.14±1.94μM for Reference Example 7. Example 8 was 29.14 ± 2.74 μM, and Reference Example 9 was 31.20 ± 2.3 μM, showing no difference in loading amount depending on the concentration of vitamin E.

Experimental Example 4

For the contact lenses of Reference Examples 4 to 9, the physical properties of rutin being released were evaluated in the same manner as described in Experimental Example 2 above.

Figures 4 and 5 show the results of evaluating the amount of rutin released from the contact lenses manufactured in Reference Examples 4 to 9 of the present invention.

Referring to Figure 4, the amount of release up to the first 30 minutes is 8.65 ± 0.26 μM, 7.50 ± 0.07 μM, 6.95 ± 1.30 μM, 7.19 ± 1.03 μM, 8.57 ± 0.91 μM, and 8.40 μM for Reference Examples 4 to 9, respectively. , the initial release amount was highest in the contact lens of Reference Example 4, which was not loaded with vitamin E, followed by the contact lens of Reference Example 8. The lens with the lowest initial release amount was the contact lens of Reference Example 6. As a result of calculating the speed using the slope of each time period, the lens with the fastest release of rutin during the first 30 minutes was the contact lens of Reference Example 4 with a release speed of 17.3 μM/h. This is followed by the contact lens of Reference Example 8, which has a speed of 17.1 μM/h.

Referring to Figure 5, when the release rate (%) was calculated from the data in Figure 4, the release rates were 27.41%, 26.29%, 21.42%, 22.38%, 28.51%, and 25.49% for Reference Examples 4 to 9, respectively. The contact lens of Reference Example 8 showed the highest initial release rate, and the contact lens of Reference Example 4 showed the next highest initial release rate.

Referring to Figures 4 and 5, the cumulative amount of rutin released over 24 hours was 19.35 ± 0.24 μM, 20.15 ± 1.35 μM, and 18.71 ± 2.58 μM for Reference Examples 4 to 9, respectively, in the order of the solution concentration of vitamin E loaded. , 19.51 ± 2.58 μM, 20.86 ± 1.28 μM, and 19.14 μM, the contact lens of Reference Example 8 had the highest total emission amount, and the contact lens of Reference Example 4 had the next highest total emission amount. When this was expressed as a release rate, the contact lenses of Reference Example 5 had the best release efficiency, with 62.49%, 70.61%, 57.69%, 60.70%, 69.41%, and 58.08% for Reference Examples 4 to 9, respectively. As a result, the contact lens of Reference Example 8 had good emission efficiency.

Experimental Example 5

For the contact lenses of Example 1, Example 2, and Comparative Example 1, the physical properties of rutin being released were evaluated in the same manner as described in Experimental Example 2. Specifically, the contact lenses of Example 1, Example 2, and Comparative Example 1 were evaluated for their rutin release properties under temperature conditions of 35°C and 25°C.

Figures 6 and 7 show the results of evaluating the amount of rutin released from contact lenses manufactured in Examples 1, 2, and Comparative Example 1 of the present invention.

Referring to Figure 6, the amount of release for the first 30 minutes of each of the contact lenses manufactured in Comparative Example 1, Example 1, and Example 2 at 35°C is 6.04±0.91μM, 6.95±0.79μM, and 7.87±0.46μM, The contact lens of Example 2 had the highest initial release amount, followed by the contact lens prepared in Example 1. The contact lens with the lowest initial release amount at 35°C is the contact lens of Comparative Example 1, which does not contain a temperature-sensitive compound. As a result of calculating the speed using the slope of each time zone, the contact lens with the fastest release during the first 30 minutes was the contact lens of Example 2 with a speed of 7.87 μM/h. Next was the contact lens of Example 1 with a release rate of 6.95 μM/h, and the contact lens of Comparative Example 1 had the slowest release rate of 6.04 μM/h.

Referring to Figure 7, when the release rate (%) was calculated from the data in Figure 6, the release rates were 20.79%, 23.74%, and 29.84% for the contact lenses manufactured in Comparative Example 1, Example 1, and Example 2, respectively. The contact lens of Example 2 showed the highest initial release rate, and the contact lens of Example 1 showed the next highest initial release rate.

Referring to Figures 6 and 7, the cumulative release amount for 24 hours at 35°C is 11.86±2.57μM, 12.37±2.70μM, 13.68±1.61 in that order for the contact lenses manufactured in Comparative Example 1, Example 1, and Example 2. In μM, the contact lens of Example 2 had the highest total release amount, and the contact lens of Example 1 had the next highest total release amount. When expressed in terms of release rate, the contact lenses manufactured in Comparative Example 1, Example 1, and Example 2, in that order, were 40.84%, 42.26%, and 51.87%, with the contact lenses of Example 2 having the highest total release amount, and Example 1 Contact lenses had the next highest total amount of emissions.

Referring to Figures 6 and 7, the release amounts for the first 30 minutes of each of the contact lenses manufactured in Comparative Example 1, Example 1, and Example 2 at 25°C were 4.40±0.89μM, 5.49±0.10μM, and 5.05±1.27. In μM, the contact lens of Example 1 had the highest initial release amount, followed by lens TR10%/R. The contact lens of Comparative Example 1 had the lowest initial release amount at 25°C. As a result of calculating the release rate using the slope of each time zone, the contact lens of Example 1 had the fastest release rate of 5.49 μM/h during the first 30 minutes. Next was the contact lens of Example 2 with a release rate of 5.05 μM/h, and the slowest release rate was the contact lens of Comparative Example 1 with a release rate of 4.40 μM/h.

When expressed as a release rate (%), Comparative Example 1 was 9.70%, Example 1 was 14.17%, and Example 2 was 12.71%. The total amount of release accumulated over 24 hours at 25°C was 16.18 ± 0.85 μM, 11.62 ± 2.23 μM, and 13.06 ± 3.97 μM, in that order, for the contact lenses manufactured in Comparative Example 1, Example 1, and Example 2. The lens had the highest total emission amount. When expressed as a release rate (%), Comparative Example 1 was 35.68%, Example 1 was 29.97%, and Example 2 was 32.89%, with the contact lens of Comparative Example 1 having the highest total release amount, and the contact lens of Example 1 There were the fewest lenses.

Experimental Example 6

The antioxidant activity of the contact lenses prepared in Examples 2 and 3 was evaluated in the following manner. Specifically, DPPH evaluation was performed to measure the antioxidant power of rutin released from the contact lenses of Examples 2 and 3.

DPPH (1,1-diphenyl-2-picryl hydrazyl), a stable free radical substance, was dissolved in 95% ethanol to prepare a 57 μM solution. 1 ml of the prepared DPPH solution was added to each Eppendorf tube, and then 50 μl of rutin solution with rutin concentrations of 20 μM, 40 μM, 60 μM, 80 μM, and 100 μM were added and vortexed for 3 minutes. After standing at 25°C for 30 minutes, 300 μl was distributed into 96 well plates, and the absorbance was measured at 515 nm using a microplate reader (Microplate reader, Bio-TEK, IT/μQuant MQX200, 380 The radical scavenging ability was calculated using Equation 2.

[Equation 2]

In Equation 2 above, “scavenging” refers to radical scavenging ability, Abs _control refers to the absorbance of the DPPH solution at 515 nm, and Abs _sample refers to the absorbance of routine solutions with different concentrations at 515 nm.

Antioxidant power was calculated based on the amount of rutin released from the contact lenses prepared in Examples 2 and 3 at 35°C. Specifically, the amount of rutin released from the contact lenses prepared in Examples 2 and 3 was calculated by processing rutin by concentration in DPPH using Equation 2 above and calculating the antioxidant power through absorbance. The calculated and evaluated antioxidant power is shown in Figure 8.

Figure 8 shows the results of evaluating the antioxidant activity of contact lenses prepared in Examples 2 and 3 of the present invention.

Referring to Figure 8, it was confirmed that the maximum antioxidant power of the contact lens manufactured in Example 2 was 20.6%, and the maximum antioxidant power of the contact lens manufactured in Example 3 was 24.3%.

The foregoing detailed description illustrates and explains the invention. In addition, the foregoing merely shows and describes preferred embodiments of the present invention, and as described above, the present invention can be used in various other combinations, modifications, and environments, and the scope and scope of the inventive concept disclosed in this specification. Changes or modifications may be made within the scope of equivalent disclosure and/or skill or knowledge in the art. Accordingly, the above detailed description of the invention is not intended to limit the invention to the disclosed embodiments. Additionally, the appended claims should be construed to include other embodiments as well.

Claims (5)

A polymer matrix containing a polymer of a polymerization solution containing a polar functional group-containing (meth)acrylate-based monomer, an alkyl group-containing (meth)acrylate-based monomer, a cross-linking agent, a temperature-sensitive compound containing a polyether-based diol, and an initiator. ; and
Flavonoid compounds including rutin;
An antioxidant and antiviral contact lens wherein the concentration of the flavonoid compound is 50 μM or more and 200 μM or less.
According to paragraph 1,
Based on 100 parts by weight of the polymerization solution,
The content of the polar functional group-containing (meth)acrylate monomer is 85 parts by weight or more and 95 parts by weight or less,
The content of the alkyl group-containing (meth)acrylate monomer is 0.5 parts by weight or more and 1.0 parts by weight or less,
The content of the cross-linking agent is 0.5 parts by weight or more and 1.0 parts by weight or less,
An antioxidant and antiviral contact lens wherein the content of the temperature-sensitive compound is 3.5 parts by weight or more and 12.5 parts by weight or less.
According to paragraph 1,
An antioxidant and antiviral contact lens wherein the polar functional group-containing (meth)acrylate monomer contains a hydroxy group.
delete According to paragraph 1,
The polymer matrix further includes vitamin E,
An antioxidant and antiviral contact lens wherein the concentration of vitamin E is 0.2 w/v% or more and 1.0 w/v% or less.