CN104193890B - Preparation method of antibacterial corneal contact lenses based on crosslinking copolymerization - Google Patents
Preparation method of antibacterial corneal contact lenses based on crosslinking copolymerization Download PDFInfo
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- CN104193890B CN104193890B CN201410413666.XA CN201410413666A CN104193890B CN 104193890 B CN104193890 B CN 104193890B CN 201410413666 A CN201410413666 A CN 201410413666A CN 104193890 B CN104193890 B CN 104193890B
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Abstract
The invention provides a preparation method of a pair of antibacterial corneal contact lenses based on crosslinking copolymerization. The preparation method of the antibacterial corneal contact lenses based on the crosslinking copolymerization comprises the following steps: firstly, carrying out photopolymerization curing or thermopolymerization curing on corneal contact lens raw material monomer mixture containing an antibacterial monomer or an antibacterial monomer prepolymer, wherein the antibacterial monomer is a functional monomer containing a quaternary ammonium salt functional group and more than two unsaturated bonds, and the corneal contact lens raw material monomer mixture also comprises a polymerization initiating agent; secondly, hydrating products obtained in the step one. Compared with the existing preparation methods, such as EP2067797A1, JP11502949, JP06337378 and JP6330820, of the antibacterial corneal contact lenses, the preparation method of the antibacterial corneal contact lenses based on the crosslinking copolymerization has the advantages that a quaternary ammonium salt monomer containing two or more than two unsaturated bonds is adopted as an antibacterial main body, the crosslinking copolymerization is utilized, and the defects of the quaternary ammonium salt monomer mainly containing single unsaturated bonds that polymerization degree is low and a hydration process is difficult in a polymerization process are overcome.
Description
Technical field
The present invention relates to a kind of antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking, belong to corneal contact lenss preparation
Raw material and the technical field of preparation method.
Background technology
Soft lens (Contact Lens), is also contact lenss or corneal contact lenss, is that one kind is worn on cornea, in order to
Correct defects of vision or protect eyes eyeglass.Soft or hard according to material it include rigid, semi-hard, soft three kinds；From preparing material
See, it can be further divided into polymethyl methacrylate (PMMA), poly hydroxy ethyl acrylate (PHEMA), siloxanes
Esters of acrylic acid or acrylic acid fluorosilicone esters etc. are the soft lens of main component.In terms of service life, it is divided into day throwing, the moon again
The types such as throwing, season throwing and half a year throwing.Soft lens not only from appearance with convenience in terms of to the dioptric such as myopia, hypermetropia, astigmatism not
Positive patient brings very big improvement, and the visual field is broad, it is true to nature to regard thing.Further, since wear soft lens prevent adolescent myopia,
Astigmatism develops, and treats the aspects such as special oculopathy and has also played certain effect.Therefore, compared with common frame eyeglasses, soft lens
Increasingly welcome by colonies such as student, job market personages.Even so, soft lens is in use, due to being related in one's hands connecing
Touch and be exposed to for a long time in air, easily cause antibacterial or other microorganism in its surface accumulation phenomena, and then induce eye
Portion's disease.Such as, acute catarrhal conjunctivitises, are commonly called as pink eye disease it is simply that a kind of common acute being caused by bacterium infection is popular
Property oculopathy.Common pathogenic bacterium include staphylococcus aureuses and streptococcus.Therefore, how to avoid above-mentioned asking in wearing soft lens
Inscribe the further genralrlization important in inhibiting to soft lens.
In order to solve above-mentioned phenomenon, common nursing means be exactly wear end after soft lens is immersed in lens care liquid
In, using a small amount of antibacterial such as quaternary ammonium salt surface active agent containing in the latter etc., lens surface is carried out disinfection, cleans.
It can thus be seen that if preparing the eyeglass with antibacterial functions, directly suppression antibacterial, can be from root in its superficial growth
The easy bacterial growth in soft lens surface or other microorganism phenomenons is overcome on this.In order to prepare antibiotic property soft lens, there are two big class at present
Synthetic route：A kind of antibacterial preparation method based on silver, another kind is with quaternary ammonium salt for the syntheti c route of antibacterial main body.
Wherein, for the first route, United States Patent (USP) 5,213, disclose in 801 (CN1541119A) one kind will have anti-
The ceramic metal material of bacterium property is introduced into technology path in contact lenss.The method firstly the need of preparing silver-colored ceramic material, and its
Then above-mentioned ceramic powder is formed lens enough to tiny to making an addition in soft lens by particle diameter again.As can be seen that said process relates to
And step is more, is unsuitable in current technology, and also it is unfavorable for the variation exploitation of product.Furthermore it is possible to find to utilize this work
The lens that skill is made often lack the definition of contact lenss user requirement.For this reason, CN01822766 proposes nano-scale
Activation silver is added in soft lens monomer mixture and is polymerized, and after monomer cure, then with oxidizing, finally gives suppression
The contact lenss of growth of microorganism.Patent CN101573146 also proposes a kind of acid process preparing antimicrobial contact lenses, utilizes
Slaine carries out antibacterial, and this patent wishes to find the contact lenss technology of preparing producing homegeneous production, in preparation process, they
Process solidification eyeglass using the acidic materials including salt precursor and effective dose.Patent CN1281282C is it is also proposed that another kind of prepare road
Line, comprises silver and the polymer containing I, II, III or IV monomer in its prepared antimicrobial lenses, its structure is as follows respectively：
Taking wherein monomer I as a example, R1It is hydrogen or C1-6Alkyl, R2It is-OR3、-NH-R3、-S-(CH2)d-R3Or-(CH2)d-
R3, wherein d is 0-8；And R3For the C replacing1-6Alkyl, its substituent group is derived from one or more of following group：Carboxylic acid, sulphur
Acid, amine, narrow, acetamide, nitrile, mercaptan, C1-6Alkyl thiourea, the C of phenylthiourea1-6Alkyl disulfide, replace phenyl disulfide, take
The C in generation1-6Alkyl thiourea, and the phenylthiourea replacing, wherein C1-6Alkyl disulfide hexichol, C1-6Ureine, C1-6Alkyl sulfide
Urea, phenylurea, and phenylthiourea replacement C1-6Alkyl, halo C1-6Alkyl, halogen, hydroxyl, carboxylic acid, carboxyl, sulfonic acid, phosphoric acid, amine
Acetamide and nitrile etc..Also the functional group enumerating in similar remaining monomer I is contained in remaining monomer II, III, IV.In this route,
Silver is still the main component of antibacterial, and physical absorption or chemical coordination effect are mainly passed through in the introducing of other monomer-polymers, come
Stable or dispersion is silver-colored.Although said process, can simplify the syntheti c route of antibacterial soft lens, absorption in soft lens silver particles or from
Easily there is leakage in son, cause the anti-microbial property of eyeglass to decline in use.Meanwhile, the loss of silver can also affect on
Eyes are damaged by wearing of soft lens.
And the technology path based on quaternary ammonium salt relates generally to following patent：EP2067797A1、JP11502949、
JP06337378 and JP6330820.Wherein, the route of the first two patent report is all with type siloxane corneal contact lenss as background,
It is added to polymerization in type siloxane monomer mixture by just quaternary ammonium salts monomer to obtain.And latter two patent then concentrate on non-
Type siloxane monomer mixture is on the corneal contact lenss of main body.But no matter above-mentioned any route, in its quaternary ammonium salts monomer
All comprise a unsaturated bond and a quaternary ammonium salt group, concrete structure is as follows：
Wherein R8、R9With R10Refer to C1-18Alkyl or its replacement alkyl, X represents F, Cl, Br or I, R11For methyl or hydrogen, Z is O
Or NH
However, ours it was found that, using above-mentioned EP2067797A1, JP11502949, JP06337378 with
When antibacterial monomer in JP6330820 is polymerized, no matter later stage how hydration process, its corneal contact lenss extract all can be led
Cause apoptosis so that prepared corneal contact lenss are difficult to pass through evaluation of its biocompatibility.
Content of the invention
Goal of the invention：It is an object of the invention to provide a kind of manufacture antibacterial cornea being easy to carry out further hydration process connects
The preparation method of tactile mirror.
Technical scheme：The present invention includes a kind of antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking, including following
Step：
1) the corneal contact lenss initial monomelic mixture photopolymerization of the performed polymer containing antibacterial monomer or antibacterial monomer is solid
Change or thermal polymerization solidification：
Described antibacterial monomer is the function monomer including quaternary ammonium salt functional group and two or more unsaturated bond；Described cornea
Contact lenss initial monomelic mixture also contains polymerization initiator；
2) by step 1) the product aquation that obtains.
Further, described antibacterial monomer is the compound described in following formula：
Wherein：A isOr
R therein3For H or C1-4 alkyl；
X is Cl, Br or I；
R1 and R2 is C1-18 alkyl, C1-18 alkylene, phenyl, benzyl, C (O) NH2、
C1-18 alkylene containing substituent group, the C1-18 alkyl containing substituent group, the phenyl containing substituent group or containing substituent group
Benzyl；
Wherein, m, n are 0～20 arbitrary integer, and substituent group is one or more in following group：Halogen, hydroxyl, carboxylic
Acid.
When above-claimed cpd in the present invention uses as the raw material of corneal contact lenss polymerized monomer, can obtain with life
The antibacterial corneal contact lenss of the thing compatibility.Concrete reason is that corneal contact lenss polymerization is typically all based on radical polymerization, because
Cation group in this above-mentioned antibacterial monomer is easy for having influence on polymerization process, reduces the degree of polymerization, thus affecting further
To how monomer low to remaining in corneal contact lenss, unreacted or the degree of polymerization being removed process below.Simultaneously as after aquation
Corneal contact lenss are a kind of three-dimensional network structure, and the inside is filled with substantial amounts of hydrone.When the monomer degree of polymerization is affected,
Just easily causing the low molecule of the degree of polymerization to be bound in network structure, being difficult to be cleaned up by common hydration process, thus leading
During causing corneal contact lenss to wear, constantly there is residual polymer to discharge, eyes are damaged.And propose in this patent
Above drawback can be effectively prevented from containing two or more unsaturated bond function monomers, trace it to its cause as follows：From certain angle
Degree is seen, the cross-linking agent that its structure of the antibacterial monomer proposing here is commonly used during being similar to high molecular polymerization.Due to exist multiple not
Saturated bond, it can be in the course of the polymerization process in intermolecular bridging action of line style, so that multiple linear molecule is mutually bonded friendship
It is unified into cancellated material, improve the degree of polymerization.After forming this structure, just effectively antibacterial can be strapped in angle
In film contact lenss, it is difficult to discharge again, therefore also just improves the biocompatibility of corneal contact lenss.
Further, described step 1) in corneal contact lenss initial monomelic mixture also include in following compounds
One or more：(methyl) acrylic acid methyl ester., (methyl ester) ethyl acrylate, (methyl) n-butyl acrylate, (methyl) acrylic acid,
(methyl) acrylamide, N, N- dimethyl (methyl) acrylamide, (methyl) acrylic acid -2- hydroxyl ethyl ester, ethyl vinyl ether, just
Butyl vinyl ether, glycerol methacrylate, NVP.
Further, described step 1) in corneal contact lenss initial monomelic mixture in, described antibacterial monomer or
Ratio in corneal contact lenss initial monomelic mixture for the performed polymer of antibacterial monomer is 0.01～5%wt.
Further, described step 2) aquation be specially：By step 1) product that obtains impregnated in water, normal saline,
In buffer saline, ethanol or isopropanol, dipping temperature is 60～100 DEG C.
Further, described step 1) carry out in aggregation container, and after aggregation container sealing, then it is solid to carry out photopolymerization
Change or thermal polymerization solidification；Described photopolymerization curing reaction condition is specially：It is 250～398nm in wavelength, intensity is 4～30mW/
cm2Uviol lamp under, solidify 0.5～4 hour；Described thermal polymerization cured reaction condition is specially：Holding 18 hours at 50 DEG C, 70
Keep 5 hours at DEG C, be warming up to 100 DEG C with 2 hours from 70 DEG C, keep 7 hours at 100 DEG C.
Further, described step 1) in corneal contact lenss initial monomelic mixture also include cross-linking agent, described crosslinking
Agent is one or more of following compound：Diethylene glycol, 2,2'-ethylenedioxybis(ethanol)., butanediol and hex- 1, the two of 6- glycol or three (methyl)
Acrylate.
In the present invention, there is the compound of antibacterial effect
Referred to as antibacterial monomer.Antibacterial monomer or he
Performed polymer addition be (if employ suitable dilution when preparing polymer based on initial monomer mixture weight
Agent, then comprise described diluent.No specified otherwise below, refers both to percentage by weight), its value can with lens composition and become
Change.Its most high percentage is (as clear in eyeglass light transmittance, oxygen permeability coefficient, focal power with the physical property not damaging gained corneal contact lenss
Clear degree, liposuction and biocompatibility etc.) when antibacterial monomer percentage ratio be defined, minimum interpolation percentage ratio had with obtained eyeglass
Percentage ratio during bacteriostasis is had to be defined.
It is chain that photopolymerization refers to that the above monomer molecule initiation that excuse me (or with photosensitizer) activates into free radical and carries out
Polymerization.And thermal polymerization refers to trigger monomer polymerization at a certain temperature.
Heretofore described blank corneal contact lenss refer to not add the common corneal contact lenss of antibacterial monomer polymerization.
Above-mentioned corneal contact lenss monomer mixture refers mainly to methyl methacrylate (MMA) and hydroxyethyl methylacrylate
(HEMA) for the soft contact lenses formulations of main body.Additionally, also include a small amount of unsaturated carboxylic acid such as methacrylic acid and acrylic acid,
The alcohol that (methyl) acrylic acid replaces：As 2- ethoxy (methyl) acrylate and 2- hydroxy ethyl methacrylate；Vinyl lactam,
As NVP；And (methyl) acrylamide, such as Methacrylamide and N,N-DMAA.
Monomer mixture obtained as above, is substantially carried out free radical polymerization, therefore also needs to add appropriate free radical
Polymerization initiator the 0.01% to 5% of reaction reagent (usually).The species of radical polymerization initiator, can be according to concrete list
The species of body polymerization is selected, such as：Benzoyl peroxide, peroxidating cinnamoyl, cumene hydroperoxide, di-t-butyl peroxide
The organic peroxide polymerization initiators such as double (4- tert-butylcyclohexyl) ester of compound, peroxide two carbonic acid.Azo system can also be included
Polymerization initiator：2,2 '-azodiisobutyronitrile, 2,2 '-azo two (2,4- methyl pentane nitrile), 2,2 '-azo two (4- methoxy
Base -2,4- methyl pentane nitrile) etc..Some Photoepolymerizationinitiater initiaters include：Benzoin methylether, benzoin ethyl ether.
Whole preparation process is as follows：First by the corneal contact lenss containing polymerization initiator, antibacterial monomer and other monomer
The solution of monomer mixture is added in the aggregation container of definite shape (as the container of lens shape), after sealing, is heated
Or Light lnduced Free Radicals polymerizing curable.Generally this aggregation container is synthesized by upper and lower module, and solution is contained in the sky being formed between the two
In chamber.For heat polymerization process, can will be airtight after container be placed in the heating cabinet of heated air circulation type, by certain speed heating
Polymerization.For photo-polymerization process, need the aggregation container high using transparency.Then irradiation ultraviolet radiation or visible ray are gathered
Close.After polymerization terminates, by upper and lower mould separately, take out the corneal contact lenss after solidification and carry out hydration process.Aquation mentioned here
Process, refer to for gained corneal contact lenss to be placed in water, normal saline, buffer saline, ethanol, isopropanol dipping so as to
Solvent expansion, meanwhile, washes away in corneal contact lenss remaining, unreacted or the low monomer of the degree of polymerization.Dipping temperature is 60-100 DEG C,
In dipping process, dipping fluid exchange 2-3 time.
Term " antibacterial " refers to that corneal contact lenss show less than one or more performance：Suppression antibacterial or other microorganism
Lens grow, kills the antibacterial on the surface of the lens or in lens radius extended spot or other microorganism (antibacterial or other
Microorganism grows on lens and antibacterial or other microorganism exist on the surface of the lens be referred to as " generation of microorganism ").
The antibacterial of lens suppression at least 20%～at least 99% of the present invention or funguses produce.This antibacterial or other microorganism include but
It is not limited to those biologies present in eyes：Particularly Pseudomonas aeruginosa, staphylococcus aureuses, escherichia coli,
Candida albicans.
Compared with prior art, its advantage is the present invention：The inventive method and existing antibacterial corneal contact lenss
Preparation method is compared, and such as EP2067797A1, JP11502949, JP06337378, JP6330820 etc. compares, the difference of maximum
Point is that the inventive method employs the quaternary ammonium salts monomer containing two or more unsaturated bonds for antibacterial main body, utilizes
The strategy of copolymerzation with cross-linking, overcomes what the quaternary ammonium salts monomer based on single unsaturated bond in the past occurred in the course of the polymerization process
The shortcomings of degree of polymerization is low, hydration process is difficult.Additionally, with CN1541119A, CN01822766, CN101573146 and
The antibacterial corneal contact lenss preparation method based on silver of the propositions such as CN1281282C is compared, it is apparent that the present invention
Advantage：(1) technical process is simple, after polymerizing curable, only needs 2-3 aquation, by remaining in corneal contact lenss, unreacted or polymerization
Spend low monomer to remove；(2) because antibacterial monomer itself is exactly a kind of cross-linking agent, therefore can be not required in corneal contact lenss monomer
Add other cross-linking agent again such as in mixture：Diethylene glycol, 2,2'-ethylenedioxybis(ethanol)., butanediol and hex- 1, the two of 6- glycol or three (methyl)
Acrylate etc.；(3) due to containing two or more unsaturated bonds in antibacterial monomer, improve quaternary ammonium salts monomer
The degree of polymerization, effectively prevent during wearing, the release of residual polymer, and causes the injury of eyes.
A kind of antibacterial corneal contact lenss of copolymerzation with cross-linking proposed by the present invention prepare variation route.This route is still with quaternary ammonium salt
For antibacterial main body, with foregoing patent except that, contain two or more unsaturated bonds in its antibacterial monomer, thus improving
The degree of polymerization between antibacterial monomer and corneal contact lenss monomer in polymerization process, is effectively prevented from referring in background section
The shortcoming of other synthetic routes.
Brief description
Fig. 1 is the corneal contact lenss preparation method schematic flow sheet in the present invention；
Fig. 2 is that the antibacterial corneal contact lenss surface that staphylococcus aureuses are obtained in embodiment 14 respectively is connect with blank cornea
Bacterium colony photo in surface of the contact lens；
Fig. 3 is the experimental result picture of the embodiment of the present invention 26.
Specific embodiment
Below technical solution of the present invention is described in detail, but protection scope of the present invention is not limited to described enforcement
Example.In following examples, involved reagent and strain are all bought in Sigma Aldrich.
Commonly use following abbreviations in the following embodiments：
HEMA HEMA
DarocurTM1173 2- hydroxy-2-methyl -1- phenyl -propyl- 1- ketone
MAA methacrylic acid
DMA N, N- DMAA
NVP vinylpyrrolidone
The synthesis of embodiment 1-6 difference antibacterial monomer：
Embodiment 1
Antibacterial monomer 1, the synthesis of two (2- methylacryoyloxyethyl)-n-hexadecyl-methyl bromide ammonium
The first step, quaternized
Add 15mL acetonitrile as solvent, in single-necked flask, add N methyldiethanol amine and bromohexadecane, mole
Ratio 1:1, fill N2Deoxygenation, adds a certain amount of hydroquinone of polymerization retarder, back flow reaction 36h at 70 DEG C.After the completion of question response, take out
Filter, washing, obtain white powder product.
Second step, esterification
Add the dichloromethane solvent of 20mL in single port bottle, add mol ratio 1:2.2 quaternized products and 2- first
Base acryloyl chloride, adds a certain amount of hydroquinone, fills N2 deoxygenation, reacts 4h in ice-water bath, and after reaction stops, rotation is steamed
Send out, be recrystallized to give product with acetone/diethyl ether.
Embodiment 2
Antibacterial monomer 2, the synthesis of two (2- methylacryoyloxyethyl)-n-hexadecyl-ammonio methacrylates
The first step, quaternized
Add 15mL acetonitrile as solvent, in single-necked flask, add N methyldiethanol amine and chloro-hexadecane, mole
Ratio 1:1, fill N2 deoxygenation, add a certain amount of hydroquinone of polymerization retarder, back flow reaction 28h at 80 DEG C.After the completion of question response, take out
Filter, washing, obtain white powder product.
Second step, esterification
Second step with embodiment 1.
Embodiment 3
Antibacterial monomer 3, the synthesis of two (2- methylacryoyloxyethyl)-dodecyls-methyl bromide ammonium
The first step, with the first step of embodiment one, wherein bromohexadecane is substituted by bromododecane
Second step, esterification
Quantitative above-mentioned quaternized products and 2- methacrylic chloride, rate of charge 1 is added in single port bottle:2.2, add one
Quantitative dichloromethane as solvent, a small amount of hydroquinone (polymerization inhibitor), react in ice-water bath, rotary evaporation, with hexamethylene/benzene
(1:2) it is recrystallized to give product.
Embodiment 4
Antibacterial monomer 4, the synthesis of two (2- acrylyl oxy-ethyl)-n-hexadecyl-methyl bromide ammonium
The first step, with the first step of embodiment 1
Second step, esterification
Add the dichloromethane of 20mL as solvent in single port bottle, add mol ratio 1:2.2 quaternized products and
Acryloyl chloride, adds quantitative hydroquinone as polymerization inhibitor, fills N2 deoxygenation, and in ice-water bath, reaction 5h stops, and rotary evaporation is used
Acetone/re-crystallizing in ethyl acetate obtains product.
Embodiment 5
Antibacterial monomer 5, the synthesis of two (2- propylene oxygen ethyl)-n-hexadecyl-ammonio methacrylate
The first step, with the first step of embodiment 1
Second step, esterification
Add quantitative above-mentioned quaternized products and allyl chloride in single port bottle, add a certain amount of dichloromethane conduct
Solvent, a small amount of hydroquinone (polymerization inhibitor), react in ice-water bath, rotary evaporation, with benzene/ethyl acetate (1:1) it is recrystallized to give
Product.
Embodiment 6
Antibacterial monomer 6, the synthesis of two (to styrene methyl oxygen ethyl)-n-hexadecyl-ammonio methacrylate
The first step, with the first step of embodiment 1
Second step, esterification
Add the dichloromethane solvent of 20mL in single port bottle, add mol ratio 1:2.2 quaternized products and to chlorine
Methyl styrene, and add a certain amount of hydroquinone as polymerization inhibitor, fill N2 deoxygenation, in ice-water bath, reaction 3h stops, rotation
Evaporation, is recrystallized to give product with acetone/petroleum ether.
The monomer mixture synthetic antimicrobial corneal contact lenss with HEMA as bulk composition for embodiment 7-17
Embodiment 7
Weigh the HEMA of 1g, be added thereto to the Darocur1173 of initiator 0.4%, 0.5% antibacterial monomer 1 (is shown in Table
1), stir, after vacuum outgass, be added in polypropylene recessive glasse mould, be 398nm in wavelength, intensity 30mW/cm2's
Solidify 30 minutes under ultraviolet light, open mould, put into aquation in 60 DEG C of normal saline, remove unreacted monomer, obtain antibacterial
Property corneal contact lenss.
Embodiment 8
Weigh the HEMA of 1g, be added thereto to the different two fourth cyanogen of initiator azo (0.1%, mass ratio), 0.8% antibacterial monomer
2 (being shown in Table 1), stir, and after vacuum outgass, are added in polypropylene recessive glasse mould, keep 18 hours, at 70 DEG C at 50 DEG C
Keep 5 hours, be warming up to 100 DEG C with 2 hours from 70 DEG C, keep 7 hours at 100 DEG C.Naturally cool to room temperature post polymerization
Terminate.Open mould, put into aquation in 100 DEG C of water, remove unreacted monomer, obtain antibiotic property corneal contact lenss.
Embodiment 9
Weigh HEMA, the 0.5gNVP of 0.5g, add the acrylic acid methyl ester. of 0.08g, 0.5% antibacterial monomer 3 (being shown in Table 1),
The Darocur1173 of 0.4wt.%, as initiator, stirs, and after vacuum outgass, is added in polypropylene recessive glasse mould
The mixture obtaining is loaded in mould, subsequently in wavelength 250nm, intensity 4mW/cm2Ultraviolet light under expose 4h, make polymer
Solidification.Open mould, put into aquation in 75 DEG C of buffer salines, remove unreacted monomer, obtain antibiotic property Corneal Contact
Mirror.
Embodiment 10
Weigh the VMA of HEMA, 0.5g of 0.5g, 0.3% antibacterial monomer 4 (being shown in Table 1), 0.4% Darocur1173 conduct
Initiator, stirs, and after vacuum outgass, is added in polypropylene recessive glasse mould, keeps 23 hours at 50 DEG C, protects at 70 DEG C
Hold 5 hours, be warming up to 100 DEG C with 2 hours from 70 DEG C, keep 7 hours at 100 DEG C.Naturally cool to room temperature post polymerization knot
Bundle.Open mould, put into aquation in 80 DEG C of ethanol, remove unreacted monomer, obtain antibiotic property corneal contact lenss.
Embodiment 11
Weigh the MAA of HEMA, 0.02g of 1g, 0.6% antibacterial monomer 5 (being shown in Table 1), 0.4% Darocur1173 conduct
Initiator, stirs, and after vacuum outgass, is added in polypropylene recessive glasse mould, keeps 23 hours at 50 DEG C, protects at 70 DEG C
Hold 5 hours, be warming up to 100 DEG C with 2 hours from 70 DEG C, keep 7 hours at 100 DEG C.Naturally cool to room temperature post polymerization knot
Bundle.Open mould, put into aquation in 90 DEG C of isopropanols, remove unreacted monomer, obtain antibiotic property corneal contact lenss.
Embodiment 12
Weigh the MAA of HEMA, 0.02g of 1g, 0.4% antibacterial monomer 6 (being shown in Table 1), 0.4% Darocur1173 conduct
Initiator, stirs, and after vacuum outgass, is added in polypropylene recessive glasse mould, keeps 23 hours at 50 DEG C, protects at 70 DEG C
Hold 5 hours, be warming up to 100 DEG C with 2 hours from 70 DEG C, keep 7 hours at 100 DEG C.Naturally cool to room temperature post polymerization knot
Bundle.Open mould, put into aquation in 60 DEG C of ethanol, remove unreacted monomer, obtain antibiotic property corneal contact lenss.
Embodiment 13
With embodiment 7, but antibacterial monomer 1 addition is 2%wt.
Embodiment 14
With embodiment 10, but antibacterial monomer 4 addition is 1%wt.
Embodiment 15
With embodiment 11, but antibacterial monomer 5 addition is 2%wt.
Embodiment 16
With embodiment 12, but antibacterial monomer 6 addition is 2%wt.
Embodiment 17
With embodiment 7, but antibacterial monomer 1 addition is 5%wt.
Embodiment 18
With embodiment 8, but antibacterial monomer 2 addition is 5%wt.
Embodiment 19
With embodiment 9, but antibacterial monomer 3 addition is 5%wt.
Embodiment 20
With embodiment 10, but antibacterial monomer 4 addition is 5%wt.
Embodiment 21
With embodiment 11, but antibacterial monomer 5 addition is 5%wt.
Embodiment 22
With embodiment 12, but antibacterial monomer 6 addition is 5%wt.
The anti-microbial property evaluation of embodiment 23 corneal contact lenss
Staphylococcus aureuses antibacterial test
Anti-microbial property evaluation, basic process reference are carried out to gained corneal contact lenss in above example 1-22《QB/
The Anti-microbial Performance Tests method test of T2591-2003 antibiotic plastic》Carry out.By quantitative inoculated bacteria in Corneal Contact to be measured
On mirror, make antibacterial uniform contact sample with the method for pad pasting, after the culture of certain time, in determination sample or bacterium number,
And calculate the antibacterium rate of sample.
Detailed process is as follows：(1) material prepares, and coverlay is polyethylene film, a size of (40 ± 2) mm X (40 ± 2)
Mm, thickness are (0.05～0.1) mm.Using front using 70% alcohol solution dipping 1 minute, then with aseptic water washing, spontaneously dry.
Sample is divided into blank corneal contact lenss A and antibacterial corneal contact lenss B, and the former refers to be not added with the Corneal Contact of antimicrobial component
Mirror, test size is (50 ± 2) mm X (50 ± 2) mm.All samples through high temperature sterilize, are then rushed with sterilized water before the test
Wash, spontaneously dry.In test process, eluent used refers to the normal saline (containing a small amount of Tween 80) containing 0.8%NaCl, culture
Liquid refers to nutrient broth/normal saline solution (1:500)；(2) staphylococcus aureuses ATCC6538, using inoculating loop from golden yellow
A small amount of (scraping 1～2 ring) fresh bacterium is taken on staphylococcic culture medium, is added in culture fluid, and take turns doing 10 times and be incremented by dilution
Liquid, selection bacterial concentration is (5.0-10.0) * 105The diluent of cfu/mL is as test bacterium solution.(3) sampling test, respectively
Take 0.2mL test bacterium solution Deca on blank corneal contact lenss and antibacterial corneal contact lenss, then with sterilizing tweezers folder
Play sterilizing coverlay and be respectively overlay in its surface, make bacterium uniform contact sample, be placed in sterilizing plates, in 37 DEG C, relative humidity
Cultivate 24 hours under the conditions of RH >=90%.After end, take out sample, be separately added into 20mL eluent, repeatedly wash sample and covering
Film, after fully shaking up, take a certain amount of be inoculated in nutrient agar, 37 DEG C culture 24 hours after count plate.(4) examine
Test result to calculate, clump count * 100% in antibiotic rate (%)=(clump count in clump count-B group in A group)/A group, wherein, in A group
Clump count refers to the bacterial number being obtained by the culture of blank corneal contact lenss A surface, and in B group, clump count refers to be connect by antibacterial cornea
The bacterial number that tactile mirror B surface culture obtains.Testing result is as shown in the table：
The evaluation of its biocompatibility (cytotoxicity experiment) of embodiment 24 soft lens
In order to further comparative study contains a unsaturated double-bond and containing two unsaturated double-bonds (proposing in this patent)
The impact to later stage evaluation of its biocompatibility for the antibacterial monomer, provide the cytotoxicity result after forming eyeglass here.Wherein, one
The antibacterial monomer molecular formula of individual unsaturated double-bond is as follows：
And as a example the antibacterial 1 that is previously mentioned of two unsaturated double-bond monomers.Both additions are 2%.In vitro
Cytotoxicity experiment basic process reference《GB/T16886.5-2003 BiologicalEvaluationofMedicalDevice》Carry out, by quantitative inoculation
Cell, in soft lens to be measured and its lixiviating solution, through the culture of certain time, is observed to the form of cell.
Detailed process is as follows：(1) material prepares：24 orifice plates, tweezers, blank soft lens A, an antibacterial soft lens B (saturation
Key, in preparation process, the antibacterial monomer structural formula of addition is(front with antibacterial soft lens C
The antibacterial 1 that face is mentioned), before experiment by all material at 121 DEG C autoclaving 25min, aquesterilisa cleans repeatedly, naturally dry
Dry.Complete medium in experimentation refers to penicillin and the streptomycin of 89%DMEM, 10% hyclone and 1%.Will
Soft lens A, B and C tweezers take out and put in 24 orifice plates, add 1mL complete medium, 37 DEG C ± 2 DEG C extraction 24h, by lixiviating solution
Take out and add in new hole, get off cells trypsinised for L929, and adjust concentration of cell suspension with complete medium
For 5 × 105Individual/mL, adds cell suspension and complete medium in the hole containing lixiviating solution and eyeglass, is placed under 37 DEG C of incubators
Culture 24h, observation of cell form to shoot photo as shown in Figure 3.It is noted that above soft lens A, B and C are all in advance through phase
With the hydration process of flow process, clean and do not leach to antibacterial.In other words, remove unreacted monomer identical.As extraction
The antibacterial occurring remaining in liquid again is exactly that constantly release causes soft lens.It can be seen that after culture in 24 hours, blank right
Cell state according to soft lens A surface is good, and antibacterial soft lens B surface can not see the cell of obvious survival, cell in its lixiviating solution
Almost apoptosis.Sharp contrast therewith, after also passing through culture in 24 hours, the cell survival rate of antibacterial soft lens C Surface is permissible
Reach 50 percent, in its lixiviating solution, cell is in good condition, only indivedual apoptosis.It can be seen that what this patent proposed
The superiority of the antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking.
Examples detailed above only technology design to illustrate the invention and feature, its object is to allow person skilled in the art's energy
Solution present disclosure much of that simultaneously has to implement, and can not be limited the scope of the invention with this.All spiritual according to the present invention
Equivalent transformation or modification that essence is done, all should be included within the scope of the present invention.
Claims (6)
1. a kind of antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking is it is characterised in that comprise the following steps：
1) by photopolymerization curing for the corneal contact lenss initial monomelic mixture of the performed polymer containing antibacterial monomer or antibacterial monomer or
Thermal polymerization solidifies；
Described antibacterial monomer is the function monomer including quaternary ammonium salt functional group and two or more unsaturated bond, specially following formula institute
The compound stated：
Wherein：A is
R3For H or C1-4Alkyl,
X is Cl, Br or I,
R1With R2For C1-18Alkyl, C1-18Alkylene, phenyl, benzyl, C (O) NH2、Contain
The C of substituent group1-18Alkylene, the C containing substituent group1-18Alkyl, the phenyl containing substituent group or the benzyl containing substituent group, its
In, m, n are the arbitrary integer of 0-20, and substituent group is one or more of following group：Halogen, hydroxyl, carboxylic acid；
Described corneal contact lenss initial monomelic mixture also includes polymerization initiator；
2) by step 1) the product aquation that obtains.
2. the antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking according to claim 1 is it is characterised in that described
Step 1) in corneal contact lenss initial monomelic mixture also include one or more of following compounds：(methyl) propylene
Sour methyl ester, (methyl ester) ethyl acrylate, (methyl) n-butyl acrylate, (methyl) acrylic acid, (methyl) acrylamide, N, N- bis-
Methyl (methyl) acrylamide, (methyl) acrylic acid -2- hydroxyl ethyl ester, ethyl vinyl ether, n-butyl vinyl ether, glycerol methyl
Acrylate, NVP etc..
3. the antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking according to claim 1 and 2 it is characterised in that
Described step 1) in corneal contact lenss initial monomelic mixture in, the performed polymer of described antibacterial monomer or antibacterial monomer exists
Ratio in corneal contact lenss initial monomelic mixture is 0.01-5%wt.
4. the antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking according to claim 1 and 2 it is characterised in that
Described step 2) aquation be specially：By step 1) product that obtains impregnated in water, normal saline, buffer saline, ethanol
Or in isopropanol, dipping temperature is 60-100 DEG C.
5. the antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking according to claim 1 and 2 it is characterised in that
Described step 1) carry out in aggregation container, and after aggregation container sealing, then carry out photopolymerization curing or thermal polymerization solidification；Institute
State photopolymerization curing reaction condition to be specially：It is 250-398nm in wavelength, intensity is 4-30mW/cm2Uviol lamp under, solidification
0.5-4 hour；Described thermal polymerization cured reaction condition is specially：Keep 18 hours at 50 DEG C, keep 5 hours at 70 DEG C, with 2
Hour is warming up to 100 DEG C from 70 DEG C, keeps 7 hours at 100 DEG C.
6. the antibacterial corneal contact lenss preparation method based on copolymerzation with cross-linking according to claim 1 and 2 it is characterised in that
Described step 1) in corneal contact lenss initial monomelic mixture also include cross-linking agent, described cross-linking agent is in following compound
One or more：Diethylene glycol, 2,2'-ethylenedioxybis(ethanol)., butanediol and hex- 1, the two of 6- glycol or three (methyl) acrylate.
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| CN109135232B (en) * | 2017-06-27 | 2021-01-29 | 江南大学 | Antibacterial polymer composite material and preparation method thereof |
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| US5760100B1 (en) * | 1994-09-06 | 2000-11-14 | Ciba Vision Corp | Extended wear ophthalmic lens |
| CN102079713B (en) * | 2009-12-01 | 2014-06-04 | 南京理工大学 | Cross-linked polyquaternary ammonium salt type antibiosis monomer, preparation method of cross-linked polyquaternary ammonium salt type antibiosis monomer and application of cross-linked polyquaternary ammonium salt type antibiosis monomer in dentistry repairing materials |
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