KR102600599B1 - Manufacturing method of hydrogel contact lens having reactive oxigen species scavenging ability using reactive polypehnol - Google Patents

Abstract

The present invention relates to a method of manufacturing a contact lens with an active oxygen removal function using reactive polyphenol, in which a large amount of polyphenol is fixed to the lens through a chemical bond, so that polyphenol is not released during storage and wearing, and active oxygen removal effectiveness is achieved. This relates to a method for manufacturing excellent hydrogel contact lenses.

Description

Manufacturing method of oxygen-scavenging functional contact lenses using reactive polyphenol

The present invention relates to a method of manufacturing hydrogel contact lenses with active oxygen removal functionality using reactive polyphenols. A large amount of polyphenol is bound to the lens through a chemical bond, so that polyphenols are not released during storage and wearing, and the effectiveness of active oxygen removal is achieved. This relates to a method of manufacturing excellent hydrogel contact lenses.

Contact lenses have been widely used because they have a wider field of view than glasses and have the advantage of avoiding the cosmetic disadvantages of wearing glasses. Currently, contact lenses are used for cosmetic purposes in addition to vision correction and treatment. The market continues to grow as it expands.

These contact lenses must maintain eye safety and efficacy by directly contacting the eye, while maintaining transparency and surface wettability of the contact lens, and must be able to transmit oxygen well toward the cornea of the eye. In other words, contact lenses must be designed with clinical aspects in mind, such as protecting the eye and cornea while ensuring smooth flow of the tear layer, avoiding excessive friction between the eyelid and the eye surface, and maintaining mechanical strength (tensile strength) and biological properties. Biocompatibility, non-toxicity, optical transparency, refractive index, surface wetability, water content suitable for the cornea, swelling rate, oxygen permeability ( Conditions such as oxygen permeability must be met.

Contact lenses as described above can be broadly divided into hard contact lenses and soft contact lenses depending on the material, and are classified into vision correction, therapeutic, and cosmetic contact lenses according to function, and recently, hydrogel contact lenses. Soft contact lenses are mostly used by modern people for vision correction and treatment purposes.

Meanwhile, active oxygen in tear fluid and the eye causes oxidative damage to proteins, causes fatal eye diseases such as cataracts, and accelerates the aging of the lens and retina. Therefore, wearing lenses with an active oxygen removal function can reduce the risk of developing various eye aging and oxygen-induced eye diseases. Since prescription through contact lenses acts more efficiently within the cornea and eye than oral administration of active oxygen scavenging substances, the development of hydrogel lenses with active oxygen scavenging functions will help eye health.

Polyphenol derivatives have the function of removing active oxygen by oxidizing themselves. If the polyphenol is physically bound to the contact lens, there is the inconvenience of having to administer the polyphenol frequently to maintain the effect of removing oxygen radicals, and the maintenance time of the effective oxygen radical removal concentration is short.

The development of contact lenses with an active oxygen removal function is an area of interest for overseas multinational companies, and they are recently pioneering the related market using a mixing method using a preservative solution. The technologies owned by these companies have the fatal disadvantage of releasing oxygen radicals within a few hours of wearing them.

Therefore, it is expected that contact lenses that effectively maintain this active oxygen removal function can be developed by chemically combining reactive polyphenol materials with hydrogel contact lenses.

US Patent Publication No. US 2021-0333436 U.S. Patent Publication No. US 2019-0350956 Republic of Korea Patent Publication No. 10-2221923

The present invention was created to improve the above problems. In order to prevent the polyphenol with the active oxygen removal function from being released when stored and worn, reactive polyphenol is synthesized and fixed to the lens with a chemical covalent bond to provide the active oxygen removal function. The purpose is to provide hydrogel contact lenses and their manufacturing method.

In order to achieve the above object, the method of manufacturing a contact lens having an active oxygen removal function of the present invention is to obtain a mixed solution by mixing a monomer for forming a hydrogel with an initiator and a crosslinking agent, and injecting the mixed solution into a mold to polymerize the contact lens. It is characterized by comprising a manufacturing step, a step of synthesizing a reactive polyphenol, and a step of binding the reactive polyphenol to the contact lens to provide an active oxygen removal function.

At this time, the reactive polyphenol synthesis step includes the steps of a) reacting dopamine, a polyphenol derivative, with trichlorotriazine, and b) removing excess unreacted material through a recrystallization process and obtaining reactive polyphenol. can do.

In addition, the step of imparting the active oxygen removal function to the contact lens includes a) adding the contact lens to distilled water, adding an alkaline substance to adjust the basicity, and then stirring, b) adding the reactive polyphenol to the contact lens. Chemical fixation step. c) may include a washing step to remove unreacted substances.

In the manufacturing method of the lens according to the present invention, reactive polyphenol is synthesized and chemically fixed to the contact lens to have an active oxygen removal function. Therefore, polyphenol is not released during distribution, storage, and wearing of the lens, and It shows the effect of having appropriate active oxygen removal effect for a long period of time.

In addition, the reactive polyphenol used in the manufacturing process of the present invention can be directly applied to the existing contact lens manufacturing process and can be utilized commercially.

Figure 1 is a schematic diagram showing a method of manufacturing a hydrogel contact lens with an active oxygen removal function of the present invention.

Hereinafter, a hydrogel contact lens with an active oxygen removal function using reactive polyphenol according to a preferred embodiment of the present invention and a method for manufacturing the same will be described.

The method of manufacturing a contact lens having an active oxygen removal function of the present invention can be performed through the same process as shown in FIG. 1. That is, a contact lens manufacturing step of mixing a monomer for hydrogel formation with an initiator and a crosslinking agent to obtain a mixed solution, injecting the mixed solution into a mold to polymerize it, synthesizing a reactive polyphenol, and adding the reactive polyphenol to the contact lens. It is characterized by comprising the step of imparting an active oxygen removal function by binding.

The contact lenses contain 58 to 98% by weight of hydroxyethyl methacrylate (HEMA), 20 to 40% by weight of silicone monomer, and 0.1 to 40% by weight of N-vinyl-pyrrolidone for hydrophilicity. , forming a monomer solution containing 0.1 to 2.0% by weight of ethylene glycol dimethacrylate as a crosslinker and 0.01 to 0.5% by weight of azobisisobutyronitrile (AIBN) as an initiator, and then polymerizing it. It can be manufactured.

The lens body polymerized with the above monomer solution is hydrated and has a hydrogel structure. Hydrogel is a material with a three-dimensional hydrophilic polymer network structure that can contain a large amount of moisture. Hydrogels are made of homopolymers or copolymers and form a structurally stable three-dimensional network structure with little fluidity.

In the present invention, a hydrophilic acrylic monomer can be used as a monomer for forming hydrogel. Hydrophilic acrylic monomers include C1-C15 hydroxyalkyl methacrylate with 1 to 3 hydroxy groups substituted, C1-C15 hydroxyalkyl acrylate with 1 to 3 hydroxy groups substituted, acrylamide, It may be any one selected from vinyl pyrrolidone, glycerol methacrylate, acrylic acid, and methacrylic acid.

Specific examples of hydrophilic acrylic monomers include 2-hydroxyethyl methacrylate (HEMA), N,N-dimethyl acrylamide (DMA), and N-vinylpyrrolidone (N- Examples include vinylpyrrolidone (NVP), glycerol monomethacrylate (GMMA), and methacrylic acid (MA).

Additionally, examples of silicone monomers include tris(3-methacryloxypropyl)silane, 2-(trimethylsilyloxy)ethyl methacrylate, 3-tris(trimethylsilyloxy)silylpropyl methacrylate, and 3-methacryloxy. selected from propyl tris(trimethylsilyl)silane (MPTS), 3-methacryloxy-2-(hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane, and 4-methacryloxybutyl terminated polydimethylsiloxane, etc. It could be any one.

In addition, crosslinking agents include ethylene glycol dimethacrylate (EGDMA), acrylic acid, methacrylic acid, acrylamide, methacrylamide, and diethylene glycol dimetha. Crylate (diethylene glycol dimethacrylate), triethylene glycol dimethacrylate, or tetraethylene glycol dimethacrylate (tetraethylene glycol dimethacrylate) can be used.

It is desirable to introduce a reactive functional group capable of forming a chemical covalent bond with a hydroxyl group (-OH) in the active oxygen removal functional material. Reactive functional groups include dichlorotriazine, monochlorotriazine, trichloropyrimidine, dichloroquinoxaline, monofluorochlorotriazine, and difluorochloropyrimidine ( difluorochloropyrimidine) and the like. Additionally, reactive functional groups include vinyl sulfone and vinyl amide.

Polyphenol derivatives may be used as active oxygen removal materials having the above-mentioned reactive functional groups. Specifically, polyphenol derivatives include catechin, resveratrol, quercetin, anthocyanin, proanthocyanin, flavonoid, isoflavone, flavonoid, and tannin ( Examples include tannin, lignin, and dopamine.

The contact lens having an active oxygen removal function of the present invention is manufactured through a process of fixing a reactive polyphenol derivative to the contact lens through a chemical bond after manufacturing the hydrogel contact lens. As described above, for forming the hydrogel As the monomer, an acrylic monomer or a silicone monomer can be used.

The reactive polyphenol contains dichlorotriazine, a reactive functional group, and can form a covalent bond with a hydroxy group (-OH) under basic conditions. Additionally, the reactive polyphenol forms a covalent bond with the hydroxyl (-OH) functional group contained in the contact lens.

In one example, dopamine, a compound represented by the following chemical formula among polyphenol derivatives, was used as the reactive polyphenol.

[Chemical formula]

The reactive polyphenol can be synthesized through the following reaction formula.

[Reaction formula]

Specifically, the reactive polyphenol is synthesized including the steps of a) reacting dopamine, a polyphenol derivative, with trichlorotriazine, b) removing excess unreacted material through a recrystallization process and obtaining reactive polyphenol. You can.

The above-mentioned reactive polyphenol has a structure that combines a polyphenol portion that exhibits an active oxygen removal function and a dichlorotriazine group that can react with a hydroxy group, so it can impart an active oxygen removal function to the hydrogel contact lens of interest in the present invention. There will be.

In addition, the step of imparting the active oxygen removal function to the contact lens is a) putting the contact lens in distilled water, adding an alkaline substance to adjust the basicity, and then stirring, b) adding the reactive polyphenol to the contact lens. It may include a chemical fixation step, c) a washing step to remove unreacted substances.

Hereinafter, the present invention will be described in detail through the following experimental examples. This is for explaining the present invention in more detail, and does not limit the scope of the present invention to the following experimental examples.

<Synthesis of reactive polyphenol (dichlorotriazine-dopamine)>

Dissolve dopamine hydrochloride (1.00g, 6.53mmol), triethylamine (1.32g, 13.1mmol), and trichlorotriazine (8.43g, 45.7mmol) in 100ml of distilled water and leave at room temperature. The reaction was stirred for 12 hours. 4-(2-((4,6-dichloro-1,3,5-triazin-2-yl)amino)ethyl, a reactive polyphenol, is extracted with 200 ml of methylene chloride and precipitated by adding hexane. ) 1.1g of benzene-1,2-diol was obtained, and the compound was named dichlorotriazine-dopamine.

<Contact lens manufacturing>

HEMA monomer was used after purification of polymerization inhibitors and impurities through vacuum distillation. Dissolve 0.04 g of EGDMA and 0.04 g of AIBN in 9.92 g of HEMA solution and stir at room temperature for 1 hour to obtain a mixed solution. The mixed solution was injected into a contact lens mold and polymerized in an oven at 120°C for 30 minutes to prepare contact lenses. After removing the contact lens from the mold, the contact lens was washed in distilled water for 2 days to remove unreacted substances.

<Manufacture of active oxygen removal functional contact lenses>

The contact lenses were placed in 50 ml of distilled water, the pH was adjusted to 8 with a 0.5 M NaOH solution, and the mixture was stirred for 3 hours. Dichlorotriazine-dopamine was added to 0, 0.1, and 0.2M respectively and stirred at room temperature for 12 hours. The contact lenses were washed in distilled water for 2 days to remove unreacted substances, and were named Lens 1, 2, and 3 according to the treated dichlorotriazine-dopamine concentration as shown in the table below.

Application of active oxygen removal material Manufactured contact lens name Lens 1 Lens 2 Lens 3 Dichlorotriazine-dopamine post-treatment concentration 0 0.1M 0.2M

<Active oxygen removal function measurement test>

The oxygen radical removal properties were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, a free radical generating reagent. The DPPH reagent is purple because it contains an unpaired radical, but when it comes in contact with polyphenol, which removes the radical of DPPH, it turns yellow, confirming the characteristics of the radical scavenging function. The DPPH assay determines the radical scavenging function of a compound, and is recognized as the same as the antioxidant function of removing free radicals containing radicals, so it is a useful method used to evaluate antioxidant function.

The degree of radical scavenging of the DPPH solution was measured using a UV-vis spectrophotometer. The DPPH solution was prepared by adding 0.0079 g of DPPH to 100 mL of ethanol (0.2 mM DPPH solution). After adding 2.7 ml of the prepared DPPH solution to the vial containing the lens, the change in absorbance was measured at 517 nm while stirring at room temperature, and the radical scavenging rate was determined using the formula below.

<Active oxygen removal function measurement results>

The measured DPPH radical scavenging rate is shown in Table 2 below. In the case of control Lens 1, in which dichlorotriazine-dopamine with an active oxygen removal function was not immobilized, approximately 5% of the added DPPH radicals were removed. Lens 2 treated with 0.1M dichlorotriazine-dopamine showed a high DPPH radical removal function of about 25%, and Lens 3 treated with 0.2M showed a high DPPH radical removal function of about 53%.

lens name Initial absorbance of DPPH solution (517nm) Absorbance of DPPH solution after lens treatment for 1 hour (517nm) DPPH radical scavenging rate (%) Lens 1 0.842 0.797 5.34 Lens 2 0.632 24.9 Lens 3 0.398 52.7

From these results, it was determined that the hydrogel contact lens manufactured by the manufacturing method of the present invention exhibits excellent physical properties in terms of oxygen removal performance.

Claims (3)

A contact lens manufacturing step of mixing a monomer for forming a hydrogel with an initiator and a crosslinking agent to obtain a mixed solution, and injecting the mixed solution into a mold to polymerize it;
synthesizing reactive polyphenols;
imparting an active oxygen removal function by binding the reactive polyphenol to the contact lens;
Includes,
The step of synthesizing the reactive polyphenol is,
a) reacting dopamine, a polyphenol derivative, with trichlorotriazine;
b) removing excess unreacted material through a recrystallization process and obtaining reactive polyphenol;
A method of manufacturing a contact lens having an active oxygen removal function, comprising:
delete In claim 1,
The step of providing the active oxygen removal function to the contact lens is,
a) putting the contact lenses in distilled water, adding an alkaline substance to adjust basicity, and then stirring;
b) chemically fixing contact lenses by adding the reactive polyphenol;
c) a washing step to remove unreacted substances;
A method of manufacturing a contact lens having an active oxygen removal function, comprising: