KR101242658B1 - Hydrophilic Intraocular Lens Having High Refractive Index and a Method for Preparing Same - Google Patents

Abstract

The present invention relates to a high refractive index hydrophilic intraocular lens containing cyclosporine and a method for preparing the same, in particular by copolymerizing hydrophilic or hydrophobic aromatic (meth) acrylate, hydrophilic (meth) acrylate, hydrophobic (meth) acrylate and (meth) acrylamide. It relates to a highly refractive hydrophilic intraocular lens coated with a cyclosporine on the surface of the obtained copolymer and a method of manufacturing the same.
The intraocular lens according to the present invention can be made thin by high refractive index, can prevent the deposition of protein or fat by the hydrophilicity, prevent the occurrence of dry eye, and glistening, and the optical portion and the support portion of the intraocular lens By manufacturing the same material, it is possible to prevent the support from loosening. In addition, by containing cyclosporin, the effect of inhibiting immunorejection caused by intraocular lens transplantation and the suppression of inflammation-induced by advanced immunorejection is superior, and the effect of suppressing turbidity of the lens posterior capsule induced in late cataract is excellent.

Description

High refractive hydrophilic intraocular lens and its manufacturing method {Hydrophilic Intraocular Lens Having High Refractive Index and a Method for Preparing Same}

According to the present invention, after preparing a precursor of a high refractive hydrophilic intraocular lens, an immunosuppressive effect of blocking anti-inflammatory and graft rejection on the intraocular lens precursor and an anti-clouding agent of the capsular bag to prevent the occurrence and metastasis of epithelial cells induced after cataract surgery. It relates to a highly refractive hydrophilic intraocular lens coated with a cyclosporin having an efficacy and a method of manufacturing the same.

In general, intraocular lenses (hereinafter referred to as “IOLs”) refer to intraocular lenses implanted in the eye in place of the clouded lens of cataract patients.

Such intraocular lens implantation is a method of removing a cataract from a cataract patient and inserting an intraocular lens (artificial intraocular lens) made of artificial material as a substitute to replace the role of eyeglasses or contact lenses after surgery. Currently, many are implemented worldwide.

At this time, cataract is a disease in which the lens of the eye becomes cloudy and external light cannot be clearly formed in the retina, so that the eyesight is poor.To treat this, the cataract is removed even if it is removed and inserted into a person. It is common practice to insert an intraocular lens (artificial lens) made of various materials that do not cause complications.

Such intraocular lenses are initially US Pat. No. 4,102,567 (name of the invention: Material for fabrication of artificial intraocular lenses and hard contact lenses; As described by Applicant: American Optical Corporation), polymethylmethacrylate (PMMA) was used, but since the polymethylmethacrylate has hard physical properties, the incision is very large (5.5-7 mm), Therefore, there was a problem that the recovery rate of the patient was slow, and complications such as astigmatism appeared after the procedure.

Therefore, in order to reduce the incision and to solve the problem of astigmatism after the procedure, US Patent No. 5,233,007 (name of the invention: polysiloxanes, methods of making same and high refractive index silicones made from same; Applicant: Allergan , Inc.), polysiloxanes with flexible properties were synthesized in various ways and used as materials for intraocular lenses. The polysiloxane intraocular lens was able to reduce the incision to 4 mm or less by flexibility.

However, since the polysiloxane has a very low glass transition temperature, an intraocular lens cannot be manufactured at room temperature, and thus, the polysiloxane has to be cooled to a low temperature to produce an intraocular lens of a desired shape. In addition, the polysiloxane intraocular lens has a problem of damaging epithelial cells and the like because it is expanded rapidly after entering the incision site while folded.

In order to solve the above problem, an intraocular lens using hydrophobic acrylate was used, as described in US Patent No. 7,067,602 (Material for making hydrophobic intraocular lens; Applicant: Benz Research and Development Corporation). The hydrophobic acrylate intraocular lens can be folded into the incision site and has a characteristic of slowly unfolding after entering the incision site and can reduce the incision site to 4 mm or less. However, intraocular lenses using these hydrophobic acrylates resulted in deposition of proteins or fats and caused glistening due to blistering by phase separation.

Thus, attention has been paid to intraocular lenses using hydrophilic acrylates.

By the way, the hydrophilic acrylate absorbs water to form a hydrogel, and when the water is absorbed, the refractive index drops and the intraocular lens has to be made thick. Accordingly, the incision cannot be less than 4 mm.

On the other hand, as described in US Patent No. 6,140,438 (name of the invention: Soft intraocular lens material; Applicant: Menicon Co., Ltd.), the aryl group acrylate compound or substituted aryl group acrylate compound It was introduced to polymerize high refractive acrylate to secure high refractive index to make an intraocular lens thin, so that the incision was 4 mm or less.

However, the aryl groups or substituted aryl groups of the high refractive acrylates are mostly hydrophobic and thus still result in deposition of proteins or fats by the aryl groups used in the polymerization. In addition, it failed to suppress the inflammation-induced and immune response due to intraocular lens implantation.

In addition, the incidence of after-cataract, Posterior capsular opacity, which becomes cloudy after the treatment after surgery after cataract, reaches 20 to 50%.

Such late cataract is the cause of the development of lens epithelial cells remaining after cataract surgery. That is, after cataract surgery, cataract epithelial cells are exposed to the external environment after cataract surgery to continue proliferation, and the proliferated cells move to the back of the capsular bag, which is an empty space, so that cell deformation and proliferation continue to decrease light penetration. When the lens epithelial cells gathered in the capsular bag of the lens is completely deformed, it becomes a late cataract (see Korean Patent No. 894,042).

However, studies on intraocular lenses that do not cause such late cataracts are still insufficient.

The present invention is to solve the problem of deposition of protein or fat on the surface of the intraocular lens, the problem of inflammation caused by intraocular lens transplantation and the immune response that rejects the graft, and turbidity of the lens posterior capsule caused by the late cataract Cyclosporine-containing high refractive hydrophilic intraocular lens coated with a cyclosporin drug having a high refractive index hydrophilic intraocular lens and having anti-inflammatory properties, an immunosuppressive effect for blocking transplant rejection, and a clouding inhibitory effect of the capsular bag. It is an object to provide a method.

In order to solve the above problems, the present invention provides a cyclosporine on the surface of the copolymer obtained by copolymerizing hydrophilic or hydrophobic aromatic (meth) acrylate, hydrophilic (meth) acrylate, hydrophobic (meth) acrylate, and (meth) acrylamide. Provided is a coated high refractive hydrophilic intraocular lens.

Specifically, the present invention provides a high refractive hydrophilic intraocular lens coated with cyclosporin on the surface of a copolymer obtained by copolymerizing monomers of a) to d):

a) hydrophilic or hydrophobic aromatic (meth) acrylate represented by the following formula (1):

Wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is a direct bond or an alkyl or alkene group having 1 to 5 carbon atoms, X is oxygen, sulfur or a direct bond, and Y is hydrogen, an alcohol group, a carboxyl group , Amine group, alkyl group or phenyl group.);

b) hydrophilic (meth) acrylates comprising hydroxy alkyl (meth) acrylates or N-vinyl lactams having 1 to 20 carbon atoms;

c) hydrophobic (meth) acrylates comprising alkyl (meth) acrylates having 1 to 20 carbon atoms; And

d) (meth) acrylamide.

The present invention also provides

(1) mixing and filtering hydrophilic or hydrophobic aromatic (meth) acrylate, hydrophilic (meth) acrylate, hydrophobic (meth) acrylate, and (meth) acrylamide;

(2) adding an initiator to the filtered mixture, mixing and filtering;

(3) degassing the mixture filtered in step (2) into a gasket;

(4) The degassed mixture is 0.5 to 1 hour at 25 to 40 ° C., 4 to 8 hours at 40 ° C., 4 to 6 hours at 40 to 60 ° C., 2 to 3 hours at 60 ° C., and 7 to 60 to 130 ° C. Heating stepwise at 15 hours and 130 ° C. for 8-12 hours;

(5) cooling at 130 ° C. to 20-30 ° C. for 3-9 hours;

(6) separating the crosslinked intraocular lens precursor from the gasket after cooling and then processing and washing; And

(7) provides a method for producing a cyclosporin-containing high refractive hydrophilic intraocular lens comprising coating a cyclosporin on the washed intraocular lens precursor.

Preferably, in the manufacturing method of the high refractive hydrophilic intraocular lens, the hydrophilic or hydrophobic aromatic (meth) acrylate is represented by the following formula 1:

[Formula 1]

(Wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is a direct bond or an alkyl or alkene group having 1 to 5 carbon atoms, X is oxygen, sulfur or a direct bond, and Y is hydrogen, an alcohol group, a carboxyl group) , An amine group, an alkyl group, or a phenyl group.) Is a hydrophilic or hydrophobic aromatic (meth) acrylate represented by;

The hydrophilic (meth) acrylate is a hydrophilic (meth) acrylate comprising hydroxy alkyl (meth) acrylate or N-vinyl lactam having 1 to 20 carbon atoms; And

The hydrophobic (meth) acrylate is a hydrophobic (meth) acrylate containing an alkyl (meth) acrylate having 1 to 20 carbon atoms,

Provided is a method of manufacturing a cyclosporin-containing high refractive hydrophilic intraocular lens.

The cyclosporin-containing high-refractive hydrophilic intraocular lens can be made thinner intraocular lens by high refractive index so that the incision is reduced to less than 4 mm fast recovery speed, prevention of astigmatism, prevention of deposition of protein or fat by hydrophilicity, prevention of dry eye syndrome, By preventing the glistening and by making the optical part and the support part of the intraocular lens the same material, the support part can be prevented from being loosened. The cyclosporine content prevents the immune rejection reaction due to intraocular lens implantation and the progression of the immune rejection. The effect of suppressing inflammation-induced inflammation by reaction is excellent, and the effect of suppressing turbidity of the capsular bag that is induced in late cataract is excellent.

1 is a schematic diagram of an intraocular lens according to an embodiment of the present invention.
Figure 2 is a view showing the chemical structural formula of cyclosporin (cyclosporin A) according to an embodiment of the present invention.
Figure 3 is a view showing the chemical structural formula of the cyclosporin epoxide according to an embodiment of the present invention.
FIG. 4 is a diagram illustrating a reaction scheme showing that the cyclosporin epoxide according to one embodiment of the present invention is coated on the intraocular lens by reacting with methacrylamide of the intraocular lens.

In one aspect of the present invention, cyclosporine-containing cyclosporine is coated on the surface of the copolymer obtained by copolymerizing hydrophilic or hydrophobic aromatic (meth) acrylate, hydrophilic (meth) acrylate, hydrophobic (meth) acrylate and (meth) acrylamide. It provides a high refractive hydrophilic intraocular lens.

In a preferred embodiment, the cyclosporin-containing high refractive hydrophilic intraocular lens is a high refractive hydrophilic intraocular lens coated with a cyclosporin on the surface of the copolymer obtained by copolymerizing the monomers of a) to d):

a) hydrophilic or hydrophobic aromatic (meth) acrylate represented by the following formula (1):

[Formula 1]

Wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is a direct bond or an alkyl or alkene group having 1 to 5 carbon atoms, X is oxygen, sulfur or a direct bond, and Y is hydrogen, an alcohol group, a carboxyl group , Amine group, alkyl group or phenyl group.);

b) hydrophilic (meth) acrylates comprising hydroxy alkyl (meth) acrylates or N-vinyl lactams having 1 to 20 carbon atoms;

c) hydrophobic (meth) acrylates comprising alkyl (meth) acrylates having 1 to 20 carbon atoms; And

d) (meth) acrylamide.

Since the high refractive index hydrophilic intraocular lens containing cyclosporin can be made thinner intraocular lens by high refractive index is less than 4 mm incision area is fast recovery speed and can prevent astigmatism, prevent the deposition of protein or fat by hydrophilicity, Prevent dry eye and prevent glistening

In addition, preferably, the optical part and the support part of the intraocular lens are made of the same material, and the support part is prevented from being loosened, and by containing cyclosporin, the immune rejection reaction caused by intraocular lens transplantation and the inflammation due to the advanced immune rejection reaction The effect of inhibiting induction is excellent, and the effect of suppressing turbidity of the capsular bag that is induced in late cataract is excellent.

Here, the intraocular lens includes an integrated, three-piece or multi-body intraocular lens, and preferably, the intraocular lens is made of the same material as the optical part and the support member.

1 is a schematic diagram of an integrated intraocular lens and a three-dimensional intraocular lens. Referring to FIG. 1 as an integrated intraocular lens, a single-piece intraocular lens 100 is processed into a single-piece in which an optical 10 and an haptic 20 of the intraocular lens are connected. The intraocular lens refers to an optical lens which no longer requires a method of bonding the support 20 of the intraocular lens to the optical unit 10. In addition, a three-piece intraocular lens means an intraocular lens having three pieces including one optical part and two support parts of the intraocular lens. In addition, the multi-body intraocular lens refers to an intraocular lens having a plurality of pieces, including one optical portion and several support portions of the intraocular lens.

By making the optical part and the support part of the intraocular lens the same material, it is possible to prevent the support part from loosening over time. The loosening of the support part over time by using the optical part and the support part of the intraocular lens is different when the polypropylene or polymethyl methacrylate (PMMA) is used as the material of the support part. See Background No. 5,716,403).

However, depending on the application, the support of the intraocular lens can be manufactured using polymethyl methacrylate (PMMA).

Cyclosporine can act as an immunosuppressive agent that has anti-inflammatory efficacy and also inhibits intraocular lens transplantation side effects, and can also act as an inhibitor to suppress clouding of the capsular bag that is induced in late cataracts. It is also used as a treatment for dry eye syndrome.

Here, cyclosporin includes, but is not limited to, cyclosporin A, cyclosporin A derivatives, salts of cyclosporin A, and mixtures thereof.

2 shows the chemical structure of cyclosporin A.

Cyclosporin inhibits the active cellular substances (cytokines) secreted when T-lymphocytes in our body cause rejection of transplanted organs, mainly interleukin- 2 and gamma interferon. The mechanism binds to cyclophilin, a protein in the cytosolic liquid part of T-lymphocytes, and the cyclosporin and cyclophilin complexes contain calcineurin, which plays a role in activating interleukin-2 transcription in normal environments. Stop it. Since 1983 the use of this cyclosporine drug has significantly reduced the frequency of post-transplant rejection and the side effects of immunosuppressants. Cyclosporine was developed by Sandoz Pharmaceutical Company in Switzerland in the late 1970s and is still used as the main immunosuppressant in combination with other immunosuppressants, such as azaciopins and steroids.

Cyclosporine is also known to reduce the number of T-lymphocytes in the conjunctival tissue, inhibit cytokine production, regulate the inflammatory response of the ocular surface and lacrimal gland, and promote the production of artificial tears by increasing the number of conjunctival goblet cells. (Article title: Clinical Effect of Cyclosporin 0.05% Eye Drops in Dry Eye Syndrome; Authors: Yong-Soo Byun, Eun-Jung Chun, Sung-Keun Chung, Department of Ophthalmology and Ophthalmology, Catholic University College of Medicine; Journal of the Korean Ophthalmology, pp. 1583-1588, 2008 number). Therefore, it will play a role in promoting the production of artificial tears when there is a change in the tear gland by intraocular lens implantation.

Cyclosporin may also inhibit epithelial cells causing late cataracts. In other words, in Graefe's Arch Clin Exp Ophthalmol (1997) 235, pp180-185 (paper title: Diclofenac sodium and cyclosporin A inhibit human lens epithelial cell proliferation in culture), when cyclosporin is used at a low concentration of 2.5 mM or more, it is induced in late cataracts. The development and metastasis of epithelial cells can be suppressed to prevent clouding of the posterior capsule.

Clinical and Experimental Ophthalmology 2008, 36, pp 62-66 (Article title: Cyclosporin effectively inhibits posterior capsule opacification after phacoemulsification in rabbits: a preliminary study) As a result of examining the clouding of the capsular bag, cyclosporine has been described to prevent the clouding of the capsular bag by inhibiting the development and metastasis of epithelial cells induced in the late cataract. Here, the drug mechanism of cyclosporin, which inhibits the development and metastasis of epithelial cells to prevent turbidity of the capsular bag, is partly a cytokine, an active cell substance secreted when T-lymphocytes in our body cause rejection of transplanted organs. It is due to the inhibition of synthesis.

Cyclosporine drugs used to inhibit inflammation, inhibit transplant rejection, and reduce late cataracts in intraocular lenses are pharmaceuticals by dispersing, sandwiching, or cross-linking or placing on sandwiches Can be introduced to indicate mechanisms.

As a method of delivering a drug such as cyclosporin to an intraocular lens, it is briefly mentioned in US Patent Publication No. 2009-0232871 as a method of dispersing, locating at the intermediate or one side of a sandwich shape, and binding. have.

However, no method of drug delivery by surface coating the intraocular lens with cyclosporine is yet known.

Dispersion of the cyclosporin drug in the intraocular lens and positioning the cyclosporin drug on the middle or one side of the sandwich shape may cause a problem that the concentration of the cyclosporin drug is drastically reduced by diffusion. This sudden change in cyclosporin concentration causes first-hand side effects from overuse, and later results in little cyclosporine near the eye, indicating no drug mechanism.

On the other hand, there are two ways to bind the cyclosporin drug to the intraocular lens. One is to participate in the crosslinking (polymerization) from the beginning in the intraocular lens manufacturing step, the other is to prepare a precursor of the intraocular lens and then to coat the surface.

Participation in cyclosporine to crosslinking from the beginning has a problem that the pharmaceutical mechanism can be prevented by changing the spatial structure of the drug and combining the functional group of the drug with the acrylate functional group to form a compound having a different structure.

Surface coatings, on the other hand, do not change or minimally change the spatial structure of the drug, which is very advantageous for activating the drug and exhibiting pharmaceutical mechanisms.

In addition, the surface coating can optimize the concentration of the drug, the concentration of the cyclosporin drug can be kept constant near the site of implantation while being used as an immunosuppressant and antifogging agent in the posterior capsular bag, and the side effects of excessive or small release Very effective drug delivery method by blocking and removing cyclosporine drug from intraocular lens after it has finished its function as an anti-inhibitor and anti-clouding agent of the posterior capsule. to be.

In addition, cyclosporine drugs have a very low solubility in water, which prevents rejection by the intraocular lens implanted into the eye by making a surface coating on the intraocular lens rather than attempting to hydrophilize it and preventing the lens posterior capsule from becoming cloudy after cataract surgery. desirable.

On the other hand, the side effect of the cyclosporin drug is that the concentration of cyclosporin in the blood when the grape juice is ingested. Increasing these cyclosporine concentrations to unwanted concentrations can cause side effects, and therefore, release by methods of dispersing or placing in a sandwich structure, or surface coating methods that are not initially involved in crosslinking or dissolution. The release of cyclosporin drugs by means of economics is an economical method that allows the use of cyclosporin drugs as an immunosuppressant and antifogging agent in the posterior capsule, while minimizing side effects and using them at optimal concentrations.

The turbidity of the capsular anterior and posterior capsules appears extensively in the optics and support of the intraocular lens (see Korean Journal of Ophthalmology 2009, Vol. 50, No. 9 pp1341-1347, Fig 2, Fig 3). Coating with all cyclosporine may be a way to prevent clouding of the posterior capsule. It can also be used as a method of preventing turbidity of the capsular bag.

As indicated above, the hydrophilic or hydrophobic aromatic (meth) acrylates that can be used in the present invention can be represented by the following formula (1).

[Formula 1]

(Wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is a direct bond or an alkyl or alkene group having 1 to 5 carbon atoms, X is oxygen, sulfur or a direct bond, Y is hydrogen, an alcohol group, Carboxyl group, amine group, alkyl group or phenyl group.)

Since the high refractive index can be exhibited by containing the hydrophilic or hydrophobic aromatic (meth) acrylate represented by the formula (1), the intraocular lens can be made thin so that the incision can be 4 mm or less.

The hydrophilic (meth) acrylate used in the present invention may include hydroxy alkyl (meth) acrylate or N-vinyl lactam having 1 to 20 carbon atoms as the alkyl group, and the hydrophobic (meth) acrylate as the alkyl group has 1 to carbon atoms. 20 alkyl (meth) acrylates may be included, but are not limited to these.

The hydrophilic (meth) acrylate, together with the hydrophilic aromatic (meth) acrylate, exhibits the hydrophilicity of the intraocular lens to prevent the deposition of proteins or fats, to prevent dry eye, and to prevent glistening.

The (meth) acrylamide that can be used in the present invention is acrylamide, methacrylamide, N-methyl acrylamide, N-methyl methacrylamide, N-ethyl acrylamide, N-ethyl methacrylamide, N-propyl acrylamide , N-propyl methacrylamide, N-methylaminopropyl acrylamide, N-methylaminopropyl methacrylamide, N-ethylaminopropyl acrylamide, N-ethylaminopropyl methacrylamide, N, N-dimethyl acrylamide, N, N-dimethyl methacrylamide, N, N-diethyl acrylamide, N, N-diethyl methacrylamide, N, N-dipropyl acrylamide, N, N-dipropyl methacrylamide, N, N -Dimethylaminopropyl acrylamide, N, N-dimethylaminopropyl methacrylamide, N, N-diethylaminopropyl acrylamide and N, N-diethylaminopropyl methacrylamide It may be any one or more selected from the group consisting of, but is not limited to these.

The optical part and the support part of the intraocular lens or the intraocular lens may further include a crosslinking agent. The crosslinking agent is butanediol di (meth) acrylate, hexanediol di (meth) acrylate, ethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate, polyethylene glycol 400 di (meth) ) Acrylates, polyethylene glycol 1000 di (meth) acrylate, propyl di (meth) acrylate, butyl di (meth) acrylate, hexyl di (meth) acrylate or nonyl di (meth) acrylate. It may be, but is not limited to these.

The optical unit and the support unit of the intraocular lens or intraocular lens may further include a UV absorber. The UV absorber is 2- [2'-hydroxy-5 '-(2 "-methacryloyloxyethoxy) -3'-tert-butylphenyl] -5-methyl-2H-benzotriazole (2- [ 2'-hydroxy-5 '-(2 "-methacryloyloxyethoxy) -3'-tert-butylphenyl] -5-methyl-2H-benzotriazole; Sb-7010MA) or 2- (2'-hydroxy-3'-tetra- Butyl-5'-methylphenyl) -5- (2'-methacryloxymethyl) benzotriazole (2- (2'-Hydroxy-3'-tetra-butyl-5'-methylphenyl) -5- (2'- methacryloxymethyl) benzotriazole; T-150), but is not limited thereto.

The optical part and the support part of the intraocular lens or the intraocular lens may further include an initiator. The initiators include Azobisisobutyronitrile (AIBN), 2,2'-azobis (2,4-dimethylvaleronitrile) (2,2'-Azobis (2,4-dimethylvaleronitrile); V-65 ), Benzoyl peroxide, diisopropyl peroxy dicarbonate, t-butyl hydro peroxide, benzoin methyl ether, benzoin ethyl ether, benzoin iso Propylether, benzoin isobutylether or 2-hydroxy-2-methyl (phenyl) -1-phenyl propane-1-on, including but not limited to .

The optical unit and the support unit of the intraocular lens or the intraocular lens may further include a die. The die is l-phenylazo-3-methacryloyloxy-2-Naphthol, 2-phenylazo-4-methacryloyloxy-2-naphthol-6 2-tert-butylphenol (2-phenylazo-4-methacryloyloxyethoxy-6-tert-butylphenol) or 1-phenylazo-4-methacryloyloxynaphthalene (l-phenylazo-4-ethacryloyloxynaphthalene) It is not limited.

The cyclosporine coating may be made by reacting cyclosporine epoxide with (meth) acrylamide or hydrophilic aromatic (meth) acrylate constituting the copolymer.

FIG. 3 shows the chemical structure of the cyclosporine epoxide, and FIG. 4 shows that the cyclosporin drug is coated on the intraocular lens by reacting the cyclosporine epoxide with (meth) acrylamide of the intraocular lens.

Here, the cyclosporine epoxide may be prepared by reacting cyclosporin with m-chloroperoxybenzoic acid in the presence of anhydrous sodium carbonate.

The content of the hydrophilic or hydrophobic aromatic (meth) acrylate is 3 to 30% by weight based on the weight of the total copolymer, the content of the hydrophilic (meth) acrylate is 20 to 89.5% by weight based on the weight of the total copolymer The content of the hydrophobic (meth) acrylate may be in the range of 7 to 35% by weight based on the total weight of the copolymer and the content of the (meth) acrylamide may be in the range of 0.5 to 15% by weight based on the weight of the total copolymer. Can be.

When the content of the hydrophilic or hydrophobic aromatic (meth) acrylate is less than 3% by weight, there is a problem that the refractive index is lowered, and when the content of the hydrophilic or hydrophobic aromatic (meth) acrylate is more than 30% by weight, the refractive index is too The problem arises in that the refractive index of the desired range cannot be obtained.

In addition, when the content of the hydrophilic (meth) acrylate is less than 20% by weight, a problem occurs that the hydrophilicity is inferior, and when the content of the hydrophilic (meth) acrylate exceeds 89.5% by weight occurs a problem that turbidity occurs.

In addition, when the content of the hydrophobic (meth) acrylate is less than 7% by weight, there is a problem that the transparency is lowered, and when the content of the hydrophobic (meth) acrylate exceeds 35% by weight, the intraocular lens manufactured is too hard There is a problem.

In addition, when the content of the (meth) acrylamide is less than 0.5% by weight, there is a problem that the content of the coated cyclosporin is too small to act as an immunosuppressant and an anti-clouding agent of the posterior capsule, and the content of the (meth) acrylamide is 15 When the weight percentage is exceeded, the content of the coated cyclosporin is too high, which causes a side effect.

Hydrophilic or hydrophobic aromatic (meth) acrylate represented by the formula (1) is 2-phenylethyl acrylate (PEA), 2-phenylethyl methacrylate (PEMA), 2-phenoxyethyl acrylate (POEA), 2- Phenoxyethyl methacrylate (POEMA), 2- (2-carboxyphenyl) ethyl acrylate, 2- (3-carboxyphenyl) ethyl acrylate, 2- (4-carboxyphenyl) ethyl acrylate, 2- (2 -Carboxyphenyl) ethyl methacrylate, 2- (3-carboxyphenyl) ethyl methacrylate, 2- (4-carboxyphenyl) ethyl methacrylate, 2- (2-carboxyphenoxy) ethyl acrylate, 2- (3-carboxyphenoxy) ethyl acrylate, 2- (4-carboxyphenoxy) ethyl acrylate, 2- (2-carboxyphenoxy) ethyl methacrylate, 2- (3-carboxyphenoxy) ethyl methacryl Rate, 2- (4-carboxyphenoxy) ethyl methacrylate, 2- (2-hydroxyphenyl) ethyl acrylate , 2- (3-hydroxyphenyl) ethyl acrylate, 2- (4-hydroxyphenyl) ethyl acrylate, 2- (2-hydroxyphenyl) ethyl methacrylate, 2- (3-hydroxyphenyl ) Ethyl methacrylate, 2- (4-hydroxyphenyl) ethyl methacrylate, 2- (2-hydroxyphenoxy) ethyl acrylate, 2- (3-hydroxyphenoxy) ethyl acrylate, 2- (4-hydroxyphenoxy) ethyl acrylate, 2- (2-hydroxyphenoxy) ethyl methacrylate, 2- (3-hydroxyphenoxy) ethyl methacrylate, 2- (4-hydroxyphenoxy Ethyl methacrylate, 2- (2-aminophenyl) ethyl acrylate, 2- (3-aminophenyl) ethyl acrylate, 2- (4-aminophenyl) ethyl acrylate, 2- (2-aminophenyl ) Ethyl methacrylate, 2- (3-aminophenyl) ethyl methacrylate, 2- (4-aminophenyl) ethyl methacrylate, 2- (2-aminophenoxy) ethyl arc Late, 2- (3-aminophenoxy) ethyl acrylate, 2- (4-aminophenoxy) ethyl acrylate, 2- (2-aminophenoxy) ethyl methacrylate, 2- (3-aminophenoxy ) Ethyl methacrylate, 2- (4-aminophenoxy) ethyl methacrylate, 2- (2-alkylphenyl) ethyl acrylate, 2- (3-alkylphenyl) ethyl acrylate, 2- (4-alkyl Phenyl) ethyl acrylate, 2- (2-alkylphenyl) ethyl methacrylate, 2- (3-alkylphenyl) ethyl methacrylate, 2- (4-alkylphenyl) ethyl methacrylate, 2- (2- Alkylphenoxy) ethyl acrylate, 2- (3-alkylphenoxy) ethyl acrylate, 2- (4-alkylphenoxy) ethyl acrylate, 2- (2-alkylphenoxy) ethyl methacrylate, 2- (3-alkylphenoxy) ethyl methacrylate, 2- (4-alkylphenoxy) ethyl methacrylate, 2- (2-phenylphenyl) ethyl acrylate, 2- (3-phenylphenyl) ethyl acrylate, 2- (4-phenylphenyl) ethyl arc Relate, 2- (2-phenylphenyl) ethyl methacrylate, 2- (3-phenylphenyl) ethyl methacrylate, 2- (4-phenylphenyl) ethyl methacrylate, 2- (2-phenylphenoxy ) Ethyl acrylate, 2- (3-phenylphenoxy) ethyl acrylate, 2- (4-phenylphenoxy) ethyl acrylate, 2- (2-phenylphenoxy) ethyl methacrylate, 2- (3- Or at least one selected from the group consisting of phenylphenoxy) ethyl methacrylate and 2- (4-phenylphenoxy) ethyl methacrylate, wherein alkyl is an alkyl group having 1 to 5 carbon atoms.

The hydrophilic (meth) acrylates are 2-hydroxyethyl acrylate (HEA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl acrylate (HPA), 2-hydroxypropyl methacrylate. (HPMA), 2-hydroxybutyl acrylate (HBA), 2-hydroxybutyl methacrylate (HBMA), 2-hydroxypentyl acrylate, 2-hydroxypentyl methacrylate, dihydroxypropyl acrylate , Dihydroxypropyl methacrylate, dihydroxybutyl acrylate, dihydroxybutyl methacrylate, dihydroxypentyl acrylate, dihydroxypentyl methacrylate, N-vinylpyrrolidone (NVP), N At least one selected from the group consisting of -vinylpiperidone and N-vinylcaprolactam.

In addition, the hydrophobic (meth) acrylate is methyl acrylate (MA), methyl methacrylate (MMA), ethyl acrylate (EA), ethyl methacrylate (EMA), propyl acrylate (PA), propyl methacryl It may be at least one selected from the group consisting of latex (PMA), butyl acrylate (BA), butyl methacrylate (BMA), pentyl acrylate, pentyl methacrylate, nonyl acrylate and nonyl methacrylate. .

Preferably, the copolymer constituting the intraocular lens according to the invention is PEA / HEMA / MMA / acrylamide, PEA / HEMA / MMA / methacrylamide, PEMA / HEMA / MMA / acrylamide, PEMA / HEMA / MMA / meth Krillamide, POEA / HEMA / MMA / acrylamide, POEA / HEMA / MMA / methacrylamide, POEMA / HEMA / MMA / acrylamide, POEMA / HEMA / MMA / methacrylamide, PEA / HEMA / EMA / acrylamide, PEA / HEMA / EMA / methacrylamide, PEMA / HEMA / EMA / acrylamide, PEMA / HEMA / EMA / methacrylamide, POEA / HEMA / EMA / acrylamide, POEA / HEMA / EMA / methacrylamide, POEMA / HEMA / EMA / acrylamide, POEMA / HEMA / EMA / methacrylamide, PEA / NVP / MMA / acrylamide, PEA / NVP / MMA / methacrylamide, PEMA / NVP / MMA / acrylamide, PEMA / NVP / MMA / Methacrylamide, POEA / NVP / MMA / acrylamide, POEA / NVP / MMA / methacrylamide, POEMA / NVP / MMA / acrylamide and POEMA / NVP / MMA / methacrylamide It may be selected from the group consisting of.

Method for producing a cyclosporin-containing high refractive hydrophilic intraocular lens according to another aspect of the present invention,

(1) mixing and filtering hydrophilic or hydrophobic aromatic (meth) acrylate, hydrophilic (meth) acrylate, hydrophobic (meth) acrylate and (meth) acrylamide;

(2) adding an initiator to the filtered mixture, mixing and filtering;

(3) degassing the mixture filtered in step (2) into a gasket;

(4) The degassed mixture is 0.5 to 1 hour at 25 to 40 ° C., 4 to 8 hours at 40 ° C., 4 to 6 hours at 40 to 60 ° C., 2 to 3 hours at 60 ° C., and 7 to 60 to 130 ° C. Heating stepwise at 15 hours and 130 ° C. for 8-12 hours;

(5) cooling at 130 ° C. to 20 to 30 ° C. for 3 to 9 hours;

(6) separating the crosslinked intraocular lens precursor from the gasket after cooling and then processing and washing; And

(7) coating cyclosporin on the washed intraocular lens precursor,

The hydrophilic or hydrophobic aromatic (meth) acrylate is represented by the following Chemical Formula 1:

[Formula 1]

(Wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is a direct bond or an alkyl or alkene group having 1 to 5 carbon atoms, X is oxygen, sulfur or a direct bond, and Y is hydrogen, an alcohol group, a carboxyl group) , An amine group, an alkyl group, or a phenyl group.) Is a hydrophilic or hydrophobic aromatic (meth) acrylate represented by;

The hydrophilic (meth) acrylate is a hydrophilic (meth) acrylate comprising hydroxy alkyl (meth) acrylate or N-vinyl lactam having 1 to 20 carbon atoms; And

The hydrophobic (meth) acrylate is a hydrophobic (meth) acrylate containing an alkyl (meth) acrylate having 1 to 20 carbon atoms.

Specific examples of preferred hydrophilic or hydrophobic aromatic (meth) acrylates, hydrophilic (meth) acrylates, hydrophobic (meth) acrylates, and (meth) acrylamides which can be used in the above production method are as described above, respectively.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited by the following examples.

Example

Example  1 ~ Example  12 Guide Lens Precursor Manufacturing

The acrylate reactants of hydrophilic or hydrophobic aromatic (meth) acrylates, hydrophilic (meth) acrylates, hydrophobic (meth) acrylates, and (meth) acrylamides were mixed and filtered in the same amounts as in Table 1 below. Then, an initiator was added to the acrylate reactant, mixed, and filtered again. The mixture of filtered acrylate reactants and initiator was placed in teflon or ethylene gaskets and then degassed. The degassed mixture was heated at 25-40 ° C. for 1 hour (0.25 ° C. per minute), at 40 ° C. for 6 hours, at 40 ° C. to 60 ° C. for 5 hours (at 15 ° C. per 15 minutes), at 60 ° C. for 2.5 hours, Heated stepwise at 60-130 ° C. for 14 hours (heated at 1 ° C. intervals per 12 minutes), and at 130 ° C. for 10 hours. Then cooled from 130 ° C. to 25 ° C. for 7 hours. After cooling, the crosslinked intraocular lens precursor was separated from the gasket, processed, and washed to obtain an intraocular lens precursor having a thickness of 0.5 to 2 mm.

Example Aromatic (meth) acrylate (content) (wt%) Hydrophilic (meth) acrylate (content) (% by weight) Hydrophobic (meth) acrylate (content)
(weight%) (Meth) acrylamide (contents) (wt%) Cross-linking agent
(content)
(weight%) Initiator
(content)
(weight%) One PEA (10) HEMA (75) MMA (10) Acrylamide (4) - AIBN (1) 2 PEA (10) HEMA (80) MMA (8) Methacrylamide (1) - AIBN (1) 3 PEA (20) HEMA (60) MMA (8) Methacrylamide (10) EGDMA (1) AIBN (1) 4 PEMA (10) HEMA (75) MMA (10) Acrylamide (3) EGDMA (1) AIBN (1) 5 PEMA (10) HEMA (80) MMA (8) Methacrylamide (1) - AIBN (1) 6 PEMA (20) HEMA (60) MMA (10) Methacrylic amide (9) - V-65 (1) 7 POEA (5) HEMA (80) MMA (10) Acrylamide (4) - V-65 (1) 8 POEA (10) NVP (70) MMA (15) Methacrylamide (2) BDDMA (2) V-65 (1) 9 POEA (10) HEMA (80) MMA (7) Methacrylate (2) - AIBN (1) 10 POEMA (5) HEMA (80) MMA (10) Acrylamide (2) EGDMA (2) AIBN (1) 11 POEMA (10) HEMA (80) MMA (7) Methacrylamide (2) - AIBN (1) 12 POEMA (20) NVP (60) MMA (10) Methacrylic amide (8) EGDMA (1) AIBN (1)

In the above table,

PEA is 2-phenylethyl acrylate,

PEMA is 2-phenylethyl methacrylate,

POEA is 2-phenoxyethyl acrylate,

POEMA is 2-phenoxyethyl methacrylate,

HEMA is 2-hydroxyethyl methacrylate,

NVP is N-vinylpyrrolidone,

MMA is methyl methacrylate,

EGDMA is ethylene glycol dimethacrylate,

BDDMA is butanediol dimethacrylate,

AIBN is Azobisisobutyronitrile,

V-65 is 2,2'-azobis (2,4-dimethylvaleronitrile) (2,2'-Azobis (2,4-dimethyl valeronitrile)).

Example  13 cyclosporine Epoxide  Produce

Cyclosporin A (100 mg, 83 mmol) was added together with m-chloroperoxybenzoic acid (20 mg) and anhydrous sodium carbonate (15 mg) in 15 mL of methylene chloride and stirred overnight at room temperature. The reaction mixture was then washed with 20% aqueous sodium bisulfite solution and 10% aqueous sodium carbonate solution. The organic layer was dried over anhydrous sodium carbonate and the solvent was removed in vacuo to afford cyclosporine epoxide.

Example  14 Cyclosporine-coated integrated intraocular lens manufacturing

Each intraocular lens precursor prepared in Examples 1 to 12 and the cyclosporine epoxide (50 mg, 90 mg or 140 mg) prepared in Example 13, respectively, were placed in 15 mL THF and refluxed for 24 hours for the intraocular lens. After reacting the (meth) acrylamide of the cyclosporin epoxide and washed with water to obtain an integral intraocular lens coated with a cyclosporin.

The foregoing description is merely illustrative of the technical idea of the present invention, and various changes and modifications may be made by those skilled in the art without departing from the essential characteristics of the present invention. Therefore, the embodiments disclosed in the present invention are intended to illustrate rather than limit the scope of the present invention, and the scope of the technical idea of the present invention is not limited by these embodiments. The scope of protection of the present invention should be interpreted by the following claims, and all technical ideas falling within the scope of the present invention should be construed as being included in the scope of the present invention.

100: intraocular lens
10: optical
20: haptic

Claims (15)

A high refractive hydrophilic intraocular lens coated with a cyclosporin on the surface of the copolymer obtained by copolymerizing the monomers of a) to d):
a) 3 to 30% by weight of the hydrophilic or hydrophobic aromatic (meth) acrylate represented by the following Chemical Formula 1, based on the weight of the entire copolymer:
[Formula 1]

Wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is a direct bond or an alkyl or alkene group having 1 to 5 carbon atoms, X is oxygen, sulfur or a direct bond, and Y is hydrogen, an alcohol group, a carboxyl group , Amine group, alkyl group or phenyl group.);
b) 20 to 89.5% by weight of hydrophilic (meth) acrylate, including hydroxy alkyl (meth) acrylate or N-vinyl lactam, having 1 to 20 carbon atoms, based on the weight of the total copolymer;
c) 7 to 35% by weight of hydrophobic (meth) acrylate, including alkyl (meth) acrylates having 1 to 20 carbon atoms, based on the weight of the entire copolymer; And
d) 0.5-15% by weight of (meth) acrylamide, based on the weight of the total copolymer. The method of claim 1, wherein the copolymer is butanediol di (meth) acrylate, hexanediol di (meth) acrylate, ethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate, polyethylene Glycol 400 di (meth) acrylate, polyethylene glycol 1000 di (meth) acrylate, propyl di (meth) acrylate, butyl di (meth) acrylate, hexyl di (meth) acrylate and nonyl di ( High refractive index hydrophilic intraocular lens characterized in that it further comprises a crosslinking agent selected from the group consisting of meth) acrylate. The method of claim 1, wherein the copolymer is 2- [2'-hydroxy-5 '-(2 "-methacryloyloxyethoxy) -3'-tert-butylphenyl] -5-methyl-2H-benzo Triazole (2- [2'-hydroxy-5 '-(2 "-methacryloyloxyethoxy) -3'-tert-butylphenyl] -5-methyl-2H-benzotriazole; Sb-7010MA) and 2- (2'-hydroxy -3'-tetra-butyl-5'-methylphenyl) -5- (2'-methacryloxymethyl) benzotriazole (2- (2'-Hydroxy-3'-tetra-butyl-5'-methylphenyl)- A high refractive hydrophilic intraocular lens further comprising a UV absorber selected from the group consisting of 5- (2'-methacryloxymethyl) benzotriazole; T-150). The method of claim 1, wherein the copolymer is azobisisobutyronitrile (AIBN), 2,2'-azobis (2,4-dimethylvaleronitrile) (2,2'-Azobis (2,4). -dimethylvaleronitrile; V-65), benzoyl peroxide, diisopropyl peroxy dicarbonate, t-butyl hydro peroxide, benzoin methyl ether, benzo Group consisting of inethyl ether, benzoin isopropyl ether, benzoin isobutyl ether and 2-hydroxy-2-methyl (phenyl) -1-phenyl propane-1-on The high refractive index hydrophilic intraocular lens further comprises an initiator selected from. The method of claim 1, wherein the copolymer is 1-phenylazo-3-methacryloyloxy-2-naphthol (l-phenylazo-3-methacryloyloxy-2-Naphthol), 2-phenylazo-4-methacryloyloxy Group consisting of 2-phenylazo-4-methacryloyloxyethoxy-6-tert-butylphenol and 1-phenylazo-4-methacryloyloxynaphthalene (l-phenylazo-4-ethacryloyloxynaphthalene) The high refractive index hydrophilic intraocular lens further comprises a die selected from. The high refractive hydrophilic intraocular lens of claim 1, wherein the cyclosporin coating is made by reacting cyclosporine epoxide with (meth) acrylamide or hydrophilic aromatic (meth) acrylate constituting the copolymer. The high refractive hydrophilic intraocular lens according to claim 6, wherein the cyclosporine epoxide is made by reacting cyclosporin with m-chloroperoxybenzoic acid in the presence of anhydrous sodium carbonate. delete According to claim 1, wherein the hydrophilic or hydrophobic aromatic (meth) acrylate represented by formula 1 is 2-phenylethyl acrylate (PEA), 2-phenylethyl methacrylate (PEMA), 2-phenoxyethyl acrylic Rate (POEA), 2-phenoxyethyl methacrylate (POEMA), 2- (2-carboxyphenyl) ethyl acrylate, 2- (3-carboxyphenyl) ethyl acrylate, 2- (4-carboxyphenyl) ethyl Acrylate, 2- (2-carboxyphenyl) ethyl methacrylate, 2- (3-carboxyphenyl) ethyl methacrylate, 2- (4-carboxyphenyl) ethyl methacrylate, 2- (2-carboxyphenoxy ) Ethyl acrylate, 2- (3-carboxyphenoxy) ethyl acrylate, 2- (4-carboxyphenoxy) ethyl acrylate, 2- (2-carboxyphenoxy) ethyl methacrylate, 2- (3- Carboxyphenoxy) ethyl methacrylate, 2- (4-carboxyphenoxy) ethyl methacrylate, 2- (2-hydroxy Phenyl) ethyl acrylate, 2- (3-hydroxyphenyl) ethyl acrylate, 2- (4-hydroxyphenyl) ethyl acrylate, 2- (2-hydroxyphenyl) ethyl methacrylate, 2- (3 -Hydroxyphenyl) ethyl methacrylate, 2- (4-hydroxyphenyl) ethyl methacrylate, 2- (2-hydroxyphenoxy) ethyl acrylate, 2- (3-hydroxyphenoxy) ethyl acrylic Late, 2- (4-hydroxyphenoxy) ethyl acrylate, 2- (2-hydroxyphenoxy) ethyl methacrylate, 2- (3-hydroxyphenoxy) ethyl methacrylate, 2- (4 -Hydroxyphenoxy) ethyl methacrylate, 2- (2-aminophenyl) ethyl acrylate, 2- (3-aminophenyl) ethyl acrylate, 2- (4-aminophenyl) ethyl acrylate, 2- ( 2-aminophenyl) ethyl methacrylate, 2- (3-aminophenyl) ethyl methacrylate, 2- (4-aminophenyl) ethyl methacrylate, 2- (2-a Nophenoxy) ethyl acrylate, 2- (3-aminophenoxy) ethyl acrylate, 2- (4-aminophenoxy) ethyl acrylate, 2- (2-aminophenoxy) ethyl methacrylate, 2- (3-aminophenoxy) ethyl methacrylate, 2- (4-aminophenoxy) ethyl methacrylate, 2- (2-alkylphenyl) ethyl acrylate, 2- (3-alkylphenyl) ethyl acrylate, 2- (4-alkylphenyl) ethyl acrylate, 2- (2-alkylphenyl) ethyl methacrylate, 2- (3-alkylphenyl) ethyl methacrylate, 2- (4-alkylphenyl) ethyl methacrylate , 2- (2-alkylphenoxy) ethyl acrylate, 2- (3-alkylphenoxy) ethyl acrylate, 2- (4-alkylphenoxy) ethyl acrylate, 2- (2-alkylphenoxy) ethyl Methacrylate, 2- (3-alkylphenoxy) ethyl methacrylate, 2- (4-alkylphenoxy) ethyl methacrylate, 2- (2-phenylphenyl) ethyl acrylate, 2- (3-phenyl Phenyl) ethyl acrylate, 2- (4-phenylphenyl) ethyl acrylate, 2- (2-phenylphenyl) ethyl methacrylate, 2- (3-phenylphenyl) ethyl methacrylate, 2- (4-phenylphenyl) ethyl methacrylate, 2 -(2-phenylphenoxy) ethyl acrylate, 2- (3-phenylphenoxy) ethyl acrylate, 2- (4-phenylphenoxy) ethyl acrylate, 2- (2-phenylphenoxy) ethyl methacryl High refractive hydrophilic intraocular lens, wherein alkyl is at least one selected from the group consisting of latex, 2- (3-phenylphenoxy) ethyl methacrylate and 2- (4-phenylphenoxy) ethyl methacrylate. Alkyl group of 1 to 5 carbon atoms. The method of claim 1, wherein the hydrophilic (meth) acrylate is 2-hydroxyethyl acrylate (HEA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl acrylate (HPA), 2- Hydroxypropyl methacrylate (HPMA), 2-hydroxybutyl acrylate (HBA), 2-hydroxybutyl methacrylate (HBMA), 2-hydroxypentyl acrylate, 2-hydroxypentyl methacrylate, Dihydroxypropyl acrylate, dihydroxypropyl methacrylate, dihydroxybutyl acrylate, dihydroxybutyl methacrylate, dihydroxypentyl acrylate, dihydroxypentyl methacrylate, N-vinylpyrroli High refractive index hydrophilic intraocular lens, characterized in that any one or more selected from the group consisting of money (NVP), N-vinyl piperidone and N-vinyl caprolactam. The method of claim 1, wherein the hydrophobic (meth) acrylate is methyl acrylate (MA), methyl methacrylate (MMA), ethyl acrylate (EA), ethyl methacrylate (EMA), propyl acrylate (PA) , Any one or more selected from the group consisting of propyl methacrylate (PMA), butyl acrylate (BA), butyl methacrylate (BMA), pentyl acrylate, pentyl methacrylate, nonyl acrylate and nonyl methacrylate High refractive index hydrophilic intraocular lens characterized by. The method of claim 1, wherein the (meth) acrylamide is acrylamide, methacrylamide, N-methyl acrylamide, N-methyl methacrylamide, N-ethyl acrylamide, N-ethyl methacrylamide, N-propyl acryl Amide, N-propyl methacrylamide, N-methylaminopropyl acrylamide, N-methylaminopropyl methacrylamide, N-ethylaminopropyl acrylamide, N-ethylaminopropyl methacrylamide, N, N-dimethyl acrylamide , N, N-dimethyl methacrylamide, N, N-diethyl acrylamide, N, N-diethyl methacrylate, N, N-dipropyl acrylamide, N, N-dipropyl methacrylamide, N, N-dimethylaminopropyl acrylamide, N, N-dimethylaminopropyl methacrylamide, N, N-diethylaminopropyl acrylamide and N, N-diethylaminopropyl methacrylamide Hydrophilic high refractive intraocular lens, characterized in that at least any one selected from the group true. The method of claim 1, wherein the copolymer is PEA / HEMA / MMA / acrylamide, PEA / HEMA / MMA / methacrylamide, PEMA / HEMA / MMA / acrylamide, PEMA / HEMA / MMA / methacrylamide, POEA / HEMA / MMA / acrylamide, POEA / HEMA / MMA / methacrylamide, POEMA / HEMA / MMA / acrylamide, POEMA / HEMA / MMA / methacrylamide, PEA / HEMA / EMA / acrylamide, PEA / HEMA / EMA / Methacrylamide, PEMA / HEMA / EMA / acrylamide, PEMA / HEMA / EMA / methacrylamide, POEA / HEMA / EMA / acrylamide, POEA / HEMA / EMA / methacrylamide, POEMA / HEMA / EMA / acrylamide Amide, POEMA / HEMA / EMA / methacrylamide, PEA / NVP / MMA / acrylamide, PEA / NVP / MMA / methacrylamide, PEMA / NVP / MMA / acrylamide, PEMA / NVP / MMA / methacrylamide, Selected from the group consisting of POEA / NVP / MMA / acrylamide, POEA / NVP / MMA / methacrylamide, POEMA / NVP / MMA / acrylamide and POEMA / NVP / MMA / methacrylamide Hydrophilic high refractive intraocular lens, characterized in that. (1) 3 to 30% by weight hydrophilic or hydrophobic aromatic (meth) acrylate, 20 to 89.5% by weight hydrophilic (meth) acrylate, 7 to 35% by weight hydrophobic (meta), based on the weight of the total copolymer ) Acrylate, and 0.5-15% by weight of (meth) acrylamide after mixing and filtering;
(2) adding an initiator to the filtered mixture, followed by filtration;
(3) degassing the mixture filtered in step (2) into a gasket;
(4) The degassed mixture is 0.5 to 1 hour at 25 to 40 ° C., 4 to 8 hours at 40 ° C., 4 to 6 hours at 40 to 60 ° C., 2 to 3 hours at 60 ° C., and 7 to 60 to 130 ° C. Heating stepwise at 15 hours, and 130 ° C. for 8-12 hours;
(5) cooling at 130 ° C. to 20-30 ° C. for 3-9 hours;
(6) separating the crosslinked intraocular lens precursor from the gasket after cooling, followed by processing and washing; And
(7) coating cyclosporin on the washed intraocular lens precursor
As a method of manufacturing a high refractive hydrophilic intraocular lens containing a cyclosporine containing,
The hydrophilic or hydrophobic aromatic (meth) acrylate is represented by the following Chemical Formula 1:
[Formula 1]

(Wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is a direct bond or an alkyl or alkene group having 1 to 5 carbon atoms, X is oxygen, sulfur or a direct bond, and Y is hydrogen, an alcohol group, a carboxyl group) , An amine group, an alkyl group or a phenyl group).
The hydrophilic (meth) acrylate is a hydrophilic (meth) acrylate comprising hydroxy alkyl (meth) acrylate or N-vinyl lactam having 1 to 20 carbon atoms; And
The hydrophobic (meth) acrylate is a hydrophobic (meth) acrylate containing an alkyl (meth) acrylate having 1 to 20 carbon atoms,
A method for producing a high refractive hydrophilic intraocular lens containing cyclosporin. The highly refractive hydrophilic intraocular lens according to any one of claims 1 to 7, and 9 to 13, wherein the optical portion and the support member of the intraocular lens are made of the same material.

Images