CN101365707A - Polymerizable silicon-containing monomer bearing pendant cationic hydrophilic groups - Google Patents
Polymerizable silicon-containing monomer bearing pendant cationic hydrophilic groups Download PDFInfo
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- CN101365707A CN101365707A CNA2007800019542A CN200780001954A CN101365707A CN 101365707 A CN101365707 A CN 101365707A CN A2007800019542 A CNA2007800019542 A CN A2007800019542A CN 200780001954 A CN200780001954 A CN 200780001954A CN 101365707 A CN101365707 A CN 101365707A
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Abstract
The invention relates to polymerizable silicon-containing monomer bearing pendant cationic hydrophilic groups. The present invention relates to polymeric compositions useful in the manufacture of biocompatible medical devices. More particularly, the present invention relates to novel siloxanyl random copolymers bearing polymerizable activated unsaturated end-groups and containing a hydrophilic, cationic substituent in the polymer chain which are capable of polymerization to form transparent polymeric compositions having high water contents; characteristics useful in the manufacture of ophthalmic devices. The polymeric compositions comprises polymerized polymerizable silicone bearing pendant cationic hydrophilic groups.
Description
Technical field
The present invention relates to polymeric compounds, it is used for the preparation of biocompatibility medical apparatus.More particularly, the invention particularly relates to novel siloxanes random copolymers, it has the unsaturated end group of polymerisable activatory in polymeric chain, and comprises the wetting ability cationic substituent, polymerization can take place, and generates the transparent polymeric composition of high-moisture; This characteristic can be used for the preparation of device for eyes.Polymeric composition comprises polymeric polymerizable silicon-containing monomer, and it has cationic hydrophilic group side group.
Background technology
Various products comprises biomedical devices, forms by containing organosilyl material.A class organosilicon material that is used for biomedical devices such as soft contact lens is siliceous hydrogel material.Hydrogel is to contain the hydration of the water that is in equilibrium state and crosslinked polymerization system.Hydrogel contact lens provides higher relatively oxygen-permeable and required biocompatibility and comfortableness.Comprise that in aqueogel material provides higher oxygen-permeable usually, because the silicon based material has the oxygen-permeable higher than water.
Another kind of organosilicon material is rigidity and the gas-pervious material that is used for hard contact lenses.This material is formed by silicon or fluorine-silicon copolymer thing usually.These materials are oxygen flows, and than the material that is used for soft contact lens rigidity more.The organosilyl material that contains that is used for comprising the biomedical devices of contact lens is disclosed in following United States Patent (USP): U.S. Patent No. 4,686,267 (people such as Ellis); U.S. Patent No. 5,034,461 (people such as Lai); With U.S. Patent No. 5,070,215 (people such as Bambury).
Usually, make soft contact lens material, described hydrophilic monomer such as methacrylic acid 2-hydroxyethyl ester, N-vinyl-2-Pyrrolidone and their combination by polymerization and crosslinking hydrophilic monomer.The polymkeric substance itself that makes by these hydrophilic monomers of polymerization shows significant wetting ability, and the big water gaging in can absorbing polymer matrix.Because absorb the ability of water, these polymkeric substance often are known as " hydrogel ".These hydrogels are optically transparent, and because high-caliber hydration is a material of making the soft contact lens particularly suitable.Because basic uncompatibility, the oxygen-permeable of silica alkyl polymer uniqueness make it be difficult to mix with high aqueous hydrogel material.Well-known is that siloxane-type monomers solvability in water and hydrophilic solvent and monomer is relatively poor, therefore, uses the standard hydrogel technology to be difficult to copolymerization and processing.Therefore, need a kind of novel siloxane-type monomers, it has the solubleness at the material that is used for preparing hydrogel lens that improved.Monomer disclosed herein is the prepolymer of siloxanes base system, have wetting ability cationic quaternary amine side group and polymerisable end-blocking, be used to have the hydrogel material of high adjustable hydrophilic siloxanes base system, increased consistency simultaneously with hydrophilic monomer and hydrophobic monomer, prepolymer, thinner, initiator and other additives.
The invention provides novel positively charged ion and contain organic silicon monomer, it is used for for example goods, and the biological example medical apparatus comprises contact lens.
Summary of the invention
First aspect the present invention relates to the cationic random copolymers of formula (I):
Formula (I)
Wherein x is 0 to 1000, and y is 1 to 300, and L is a linking group and each other can be identical or different; X-is with unicharged counter ion at least; N is from 1 to about 300 integer; Each R1 and R2 are hydrogen independently, the C1-C30 alkyl of straight chain or cladodification, C1-C30 fluoroalkyl, the C1-C20 ester group, alkyl oxide, cycloalkyl ethers, cycloalkenyl group ether, aryl ethers, aralkyl ethers contains the group of polyethers, urea groups, amide group, amido replaces or unsubstituted C1-C30 alkoxyl group, replace or unsubstituted C3-C30 cycloalkyl, replace or unsubstituted C3-C30 cycloalkenyl group, replace or unsubstituted C5-C30 aryl, replace or unsubstituted C5-C30 aralkyl, replace or unsubstituted C5-C30 heteroaryl, replace or unsubstituted C3-C30 heterocycle, replace or unsubstituted C4-C30 Heterocyclylalkyl, replace or unsubstituted C6-C30 heteroarylalkyl, fluorine, the C5-C30 fluoro aryl, or hydroxyl and A are polymerisable vinyl segments.
The example of typical linking group comprises divalent group as used herein, comprises urethanum (urethanes), carbonic ether; carbamate (carbamates); the carboxyl urea groups, alkylsulfonyl, the C1-C30 alkyl of straight chain or cladodification; the C1-C30 fluoroalkyl; the C1-C20 ester group, alkyl oxide, cycloalkyl ethers; cycloalkenyl group ether; aryl ethers, aralkyl ethers contains the group of polyethers; urea groups; amide group, amido replaces or unsubstituted C1-C30 alkoxyl group; replace or do not replace the C3-C30 cycloalkyl; replace or unsubstituted C3-C30 cycloalkenyl group, replace or unsubstituted C5-C30 aryl, replace unsubstituted C5-C30 aralkyl; replace or unsubstituted C5-C30 heteroaryl; replace or unsubstituted C3-C30 heterocycle, replace or unsubstituted C4-C30 Heterocyclylalkyl, replace unsubstituted C6-C30 heteroarylalkyl; C5-C30 fluoro aryl, or the alkyl oxide of hydroxyl replacement and their combination.
The representative example of the urethanum that uses among the present invention comprises the secondary amine that for example is connected with carboxyl, and wherein carboxyl can also be connected with other groups such as alkyl.Equally, secondary amine can also be connected with other groups such as alkyl.
The representative example of the carbonic ether that uses among the present invention comprises for example alkyl carbonate and aryl carbonates, or the like.
The representative example of the carbamate that uses among the present invention comprises for example alkyl carbamate and aryl carbamate, or the like.
The representative example of the carboxyl urea groups that uses among the present invention comprises for example alkyl carboxyl urea groups and aryl carboxyl urea groups, or the like.
The representative example of the alkylsulfonyl that uses among the present invention comprises for example alkyl sulphonyl and aryl sulfonyl, or the like.
The representative example of the alkyl that uses among the present invention comprises, for example, be connected to described molecule rest part contain carbon and hydrogen atom have 1 to the straight chain of about 18 carbon atoms or the saturated or undersaturated hydrocarbon chain group of cladodification, for example, methyl, ethyl, n-propyl, 1-methylethyl (sec.-propyl), normal-butyl and n-pentyl, or the like.
The representative example of the fluoroalkyl that uses among the present invention comprises the above-mentioned straight chain that for example has the one or more fluorine atoms that are connected with carbon atom or the alkyl of cladodification, for example, and-CF
3,-CF
2CF
3,-CH
2CF
3,-CH
2CF
2H and-CF
2H, or the like.
The representative example of the ester group that uses among the present invention comprises the carboxylicesters that for example has 1-20 carbon atom, or the like.
Ether that uses among the present invention or the representative example that contains the group of polyethers comprise for example alkyl oxide, cycloalkyl ethers, cycloalkenyl group ether, aryl ethers, aryl alkyl ethers, alkyl wherein, cycloalkyl, cycloalkenyl group, aryl and arylalkyl are by above-mentioned definition, for example, epoxy alkane, poly-(epoxy alkane), as oxyethane, propylene oxide, butylene oxide ring, poly-(oxyethane), poly-(ethylene glycol), poly-(propylene oxide), poly-(butylene oxide ring) and their mixture or multipolymer, the ether or the polyether group that also comprise general formula-R8OR9, wherein R8 is a key, alkyl by above-mentioned definition, cycloalkyl or aryl, R9 is the alkyl by above-mentioned definition, cycloalkyl or aryl, for example ,-CH
2CH
2OC
6H
5With-CH
2CH
2OC
2H
5, or the like.
The representative example of the amide group that uses among the present invention comprises for example acid amides of general formula-R10C (O) NR11R12, wherein R10, R11 and R12 are the C1-C30 alkyl independently, for example, R10 can be alkylidene group, arylidene, cycloalkylidene, R11 and R12 can be alkyl, aryl and the cycloalkyl by above-mentioned definition, or the like.
The representative example of the amine groups of using among the present invention comprises for example amine of general formula-R13NR14R15, wherein R13 is C2-C30 alkylidene group, arylidene or cycloalkylidene, R14 and R15 are the C1-C30 alkyl independently, for example press alkyl, aryl or the cycloalkyl of above-mentioned definition, or the like.
The representative example of the urea groups that uses among the present invention comprises for example having one or more substituent urea groups or unsubstituted urea groups.Urea groups preferably has the urea groups of 1-12 carbon atom.Substituent example comprises alkyl and aryl.The example of urea groups comprises 3-methyl urea groups, 3,3-dimethyl urea groups and 3-phenyl urea groups.
The representative example of the alkoxyl group that uses among the present invention comprises the alkyl by above-mentioned definition that for example is connected with the rest part of described molecule through the oxygen key, be general formula-OR20, wherein R20 is alkyl, cycloalkyl, cycloalkenyl group, aryl or the arylalkyl by above-mentioned definition, for example ,-OCH3 ,-OC2H5 or-OC6H5 or the like.
The representative example of the cycloalkyl of using among the present invention comprises for example about 3 to the replacement or the unsubstituted non-fragrant monocycle of about 18 carbon atoms or encircle ring system more, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, perhydro naphthyl, adamantyl and norborneol alkyl bridged ring group or spiral shell bicyclic radicals, for example, spiral shell-(4,4)-ninth of the ten Heavenly Stems-2-base or the like, randomly contain one or more heteroatomss, for example, O and N, or the like.
The representative example of the cycloalkenyl group that uses among the present invention comprises and for example contains 3 replacement or the unsubstituted groups that contain ring to about 18 carbon atoms of having an appointment, and has at least one carbon-to-carbon double bond, for example, cyclopropenyl radical, cyclobutene base and cyclopentenyl, or the like, wherein ring can randomly contain one or more heteroatomss, for example, O and N, or the like.
The representative example of the aryl that uses among the present invention comprises and for example contains 5 replacement or unsubstituted single fragrance or the many aromatic groups to about 25 carbon atoms of having an appointment, for example, phenyl, naphthyl, tetrahydro naphthyl, indenyl and xenyl or the like, randomly contain one or more heteroatomss, for example, O and N, or the like.
The representative example of the arylalkyl that uses among the present invention for example comprise with by direct-connected replacement of the alkyl of above-mentioned definition or unsubstituted aryl by above-mentioned definition, for example,-CH2C6H5 ,-C2H5C6H5, or the like, wherein aryl can randomly contain one or more heteroatomss, for example, O and N, or the like.
The representative example of the fluoro aryl that uses among the present invention comprises the aryl by above-mentioned definition that for example has one or more fluorine atoms that are connected with aryl.
The representative example of the heterocyclic group that uses among the present invention for example comprises and to replace or unsubstituted stable 3 to about 15 yuan of cyclic groups, it contains carbon atom and 1-5 heteroatoms, for example, and nitrogen, phosphorus, oxygen, sulphur and its mixing.The heterocyclic group that is fit to that the present invention uses can be monocycle, dicyclo or three-ring system, can comprise condensed ring, bridged ring or volution system, and the nitrogen in the heterocyclic group, phosphorus, carbon, oxygen or sulphur atom can be chosen wantonly and be oxidizing to various oxidation state.In addition, nitrogen-atoms can be randomly by seasonization; With cyclic group can by partially or completely saturated (that is, heteroaromatic or heteroaryl aromatic).The example of heterocyclic group includes but not limited to azetidinyl, acridyl, the benzo dioxolyl, the benzodioxan base, benzofuryl, carbazyl, the cinnolines base, dioxolanyl, the indolizine base, the naphthyridine base, perhydro azepine base, phenazinyl, phenothiazinyl phenoxazinyl, phthalazinyl, pyridyl, pteridinyl, purine radicals, quinazolyl, quinoxalinyl, quinolyl (quinolinyl), isoquinolyl, tetrazyl, imidazolyl, tetrahydroisoquinoline, piperidyl, piperazinyl, 2-oxo piperazinyl, 2-oxo-piperidine base, 2-oxo-pyrrolidine base, 2-oxo azepine base, the azepine base, pyrryl, the 4-piperidone base, pyrrolidyl, pyrazinyl, pyrimidyl, pyridazinyl oxazolyl oxazolinyl oxazolidinyl, triazolyl, indanyl isoxazolyl isoxazole alkyl, morpholinyl, thiazolyl, thiazolinyl, thiazolidyl, isothiazolyl, quinuclidinyl, the isothiazole alkyl, indyl, pseudoindoyl, the indoline base, the isoindoline base, the octahydro indyl, the octahydro pseudoindoyl, quinolyl (quinolyl), isoquinolyl, the Decahydroisoquinolinpreparation base, benzimidazolyl-, thiadiazolyl group, benzopyranyl, benzothiazolyl benzoxazolyl, furyl, tetrahydrofuran base, THP trtrahydropyranyl, thienyl, benzothienyl, the thia morpholinyl, thia morpholinyl sulfoxide, thia morpholinyl sulfone, two oxa-phospholane bases; oxadiazole base, chromanyl, isochroman base etc. and their mixture.
The representative example of the heteroaryl that uses among the present invention for example comprises replacement or the unsubstituted heterocyclic group by above-mentioned definition.The heteroaryl ring group can be connected with main structure at any heteroatoms or carbon atom place, thereby produces rock steady structure.
The representative example of the heteroarylalkyl that uses among the present invention for example comprise with by direct-connected replacement of the alkyl of above-mentioned definition or unsubstituted heteroaryl ring group by above-mentioned definition.Heteroarylalkyl can be connected with main structure at any carbon atom place of alkyl, thereby produces rock steady structure.
The representative example of the heterocyclic group that uses among the present invention comprises and for example replacing or unsubstituted heterocyclic group by above-mentioned definition.Heterocyclic group can be connected with main structure at any heteroatoms or carbon atom place, thereby produces rock steady structure.
The representative example of the Heterocyclylalkyl that uses among the present invention for example comprise with by direct-connected replacement of the alkyl of above-mentioned definition or unsubstituted heterocyclic group by above-mentioned definition.Heterocyclylalkyl can be connected with main structure at the carbon atom place of alkyl, thereby produces rock steady structure.
The representative example of " the undersaturated organic group of polymerisable ethylenic " for example comprises group, the group that contains (methyl) acrylamide, the group that contains NSC 11801, the group that contains carboxylamine ethene ester that contain (methyl) acrylate, contains cinnamic group, or the like.In one embodiment, the undersaturated organic group of polymerisable ethylenic can be represented by following general formula:
Wherein R21 is hydrogen, fluorine or methyl; R22 is hydrogen, fluorine independently, have 1-6 carbon atom alkyl or-the CO-Y-R24 group, wherein Y be-O-,-S-or-NH-, R24 has 1 divalent alkyl to about 10 carbon atoms.
The alkyl of ' replacement ', the alkoxyl group of ' replacement ', the cycloalkyl of ' replacement ', the cycloalkenyl group of ' replacement ', the arylalkyl of ' replacement ', the aryl of ' replacement ', the heterocycle of ' replacement ', the heteroaryl ring of ' replacement ', the heteroarylalkyl of ' replacement ', the heterocycloalkyl ring of ' replacement ', ' replace ring ' and ' substituting group in the carboxylic acid derivative that replaces can be identical or different, comprise one or more substituting groups, as hydrogen, hydroxyl, halogen, carboxyl, cyano group, nitro, the oxygen base (=O), sulfenyl (=S), replace or unsubstituted alkyl, replace or unsubstituted alkoxyl group, replace or unsubstituted thiazolinyl, replace or unsubstituted alkynyl, replace or unsubstituted aryl, replace or unsubstituted arylalkyl, replace or unsubstituted cycloalkyl, replace or unsubstituted cycloalkenyl group, replace or unsubstituted amino, replace or unsubstituted aryl, replace or unsubstituted heteroaryl, the heterocycloalkyl ring that replaces, replace or unsubstituted heteroarylalkyl, replace or unsubstituted heterocycle, replace or unsubstituted guanidine,-COORx,-C (O) Rx,-C (S) Rx,-C (O) NRxRy,-C (O) ONRxRy,-NRxCONRyRz,-N (Rx) SORy,-N (Rx) SO
2Ry ,-(=N-N (Rx) Ry) ,-NRxC (O) ORy ,-NRxRy ,-NRxC (O) Ry-,-NRxC (S) Ry ,-NRxC (S) NRyRz ,-SONRxRy-,-SO2NRxRy-,-ORx ,-ORxC (O) NRyRz ,-ORxC (O) ORy-,-OC (O) Rx ,-OC (O) NRxRy ,-RxNRyC (O) Rz ,-RxORy ,-RxC (O) ORy ,-RxC (O) NRyRz ,-RxC (O) Rx ,-RxOC (O) Ry ,-SRx ,-SORx ,-SO
2Rx ,-ONO
2The Rx in each above-mentioned group wherein, Ry and Rz can be identical or different, can be hydrogen atoms, replace or unsubstituted alkyl, replace or unsubstituted alkoxyl group, replace or unsubstituted thiazolinyl, replace or unsubstituted alkynyl, replace or unsubstituted aryl, replace or unsubstituted arylalkyl, replace or unsubstituted cycloalkyl, replace or unsubstituted cycloalkenyl group, replace or unsubstituted amino, replace or unsubstituted aryl, replace or unsubstituted heteroaryl, the heterocycloalkyl ring that replaces, replace or unsubstituted heteroarylalkyl, or replacement or unsubstituted heterocycle.
The cationic random copolymers of preferred formula (I) is a formula (II) as follows:
Formula (II)
Wherein, x is 0 to 1000, and y is 1 to 300.
The schematic typical example of synthetic method that is used to prepare the novel siliceous random copolymers of positively charged ion disclosed in this invention is as follows:
Aspect second, the present invention includes the goods that form by the monomer mixture that comprises formula (I) random copolymers that forms device.According to embodiment preferred, described goods are the polymerisates that comprise the above-mentioned random copolymers and at least the second monomeric mixture.Preferred goods are optically transparent, and can be used as contact lens.
The useful article of being made by these materials may require hydrophobicity, the siliceous monomer of possibility.Preferred compositions possess hydrophilic property and hydrophobic monomer.The present invention can be rigidity or flexibility applicable to various polymeric materials.Particularly preferred polymeric material is lens, comprises contact lens, lens and non-phakic intraocular lens, cornea implant, but all polymeric materials that comprise biomaterial all within the scope of the invention.Particularly preferably be and contain silicone-hydrogel.
The present invention also provides medical apparatus, as heart valve (heart valve) and ophthalmic lens, film (film), operation device, conduit surrogate, intrauterine device, film (membrane), barrier film (diaphragm), surgical implant, blood vessel, artificial ureteral, artificial breast's tissue, be used for the film that contacts with body fluid external, for example, kidney dialysis usefulness film and the heart/lung machine film or the like, conduit, mouth guard (mouth guard), denture liner (denture liner), device for eyes and particularly contact lens.
The mixture that contains at least a siliceous cationic random copolymers and at least a hydrophilic monomer by polymerization prepares and contains silicone-hydrogel.Silicon-containing monomer can be used as linking agent (linking agent is defined as having the monomer of a plurality of polymerisable functional groups), maybe can use independent linking agent.
The early stage example of siliceous contact lens material is disclosed in U.S. Patent No. 4,153,641 (people such as Deichert transfers Bausch ﹠ Lomb Incorporated).Lens are made by poly-(organo-siloxane) monomer, and it is through divalent hydrocarbyl mission α, and the ω end is bonded to polymeric activatory unsaturated group.The siliceous prepolymer of various hydrophobicitys is as 1, two (methacryloxy the alkyl)-polysiloxane of 3-and known hydrophilic monomer such as methacrylic acid 2-hydroxyethyl ester (HEMA) copolymerization.
U.S. Patent No. 5,358,995 (people such as Lai) have put down in writing the silicone-hydrogel that contains that contains with the polysiloxane prepolymers of polysiloxane group alkyl (methyl) the acrylate monomer polymeric acrylate ended of large volume and at least a hydrophilic monomer.People such as Lai transfer Bausch ﹠ LombIncorporated, and mode is by reference incorporated its full content into this paper.The polysiloxane prepolymers of acrylate ended often is called M
2D
x, constitute by two acrylate end groups, " x " is the quantity of dimethyl siloxane.Polysiloxane group alkyl (methyl) acrylate monomer of preferred large volume is TRIS-type (methacryloxypropyl three (trimethylsiloxy) silane), and wherein hydrophilic monomer contains vinylformic acid (acrylic) or vinyl.
Other examples of the operable silicon-containing monomer mixture of the present invention comprise following: U.S. Patent No. 5,070,215 and 5,610,252 (people such as Bambury) disclosed NSC 11801 and carboxylamine vinyl acetate monomer mixture; U.S. Patent No. 5,321, the disclosed fluorine silicon monomer mixture of 108,5,387,662 and 5,539,016 (people such as Kunzler); U.S. Patent No. 5,374,662,5,420,324 and 5,496,871 (people such as Lai) disclosed fumarate monomer mixture and U.S. Patent No. 5,451,651,5,648,515,5,639, the disclosed urethanum monomer mixture of 908 and 5,594,085 (people such as Lai), all these patents all transfer transferee Bausch ﹠ Lomb Incorporated, and mode is by reference incorporated its full content into this paper.
No Si hydrophobic examples of material comprises alkyl acrylate and alkyl methacrylate.
Cationic siliceous random copolymers can with various hydrophilic monomer copolymerization, form silicone hydrogel lenses.The hydrophilic monomer that is fit to comprises: undersaturated carboxylic acid, as methacrylic acid and vinylformic acid; The alcohol that vinylformic acid replaces is as methacrylic acid 2-hydroxyethyl ester and vinylformic acid 2-hydroxyethyl ester; Vinyl lactam is as N-vinyl pyrrolidone (NVP) and 1-vinylazonam-2-ketone; And acrylamide, as Methacrylamide and N,N-DMAA (DMA).
Other examples are U.S. Patent No.s 5,070, disclosed close water azolactone monomer in disclosed wetting ability NSC 11801 or carboxylamine vinyl acetate monomer and the U.S. Patent No. 4,910,277 in 215.Other hydrophilic monomers that are fit to are conspicuous for those skilled in the art.
The hydrophobicity linking agent comprises methacrylic ester, as Ethylene glycol dimethacrylate (EGDMA) and allyl methacrylate(AMA) (AMA).Opposite with traditional silicon hydrogel monomer mixtures, to compare with the silicon-containing monomer of prior art, the monomer mixture that contains seasonization of the present invention (quaternized) silicon random copolymers is water-soluble relatively.The advantage that this feature provides is, because of may reducing of the incompatible muddy lens that cause of being separated, and the extraction of polymeric material used water.Yet, when needed, can also use traditional organic extraction method.In addition, the lens of extraction confirm to have made up well oxygen-permeable (Dk) and low modulus, known this are very important performances to obtaining required contact lens.In addition, even the lens with the preparation of the silicon random copolymers of seasonization of the present invention are also wettable when not carrying out surface treatment, provide dried mould to peel off, in monomer mixture, do not need solvent (but can use solvent, as glycerine), the polymeric material of extraction does not have cytotoxicity, and the surface is slick to sense of touch.When the polymeric monomer mixture of the silicon random copolymers that contains seasonization of the present invention did not show required tear strength, toughner such as TBE (the 4-tertiary butyl-2-hydroxy-cyclohexyl methacrylic ester) can be added in the monomer mixture.Other strengthening agents are well known by persons skilled in the art, and can use when needed.
Although the advantage of cationic siliceous random copolymers disclosed herein is that they are water-soluble relatively, and also is soluble, in initial monomeric mixture, can comprise organic thinner in their comonomer.Among the present invention, term " organic thinner " comprise the uncompatibility of each composition in the initial monomeric mixture is minimized and with original mixture in the nonreactive basically organic compound of each composition.In addition, organic thinner is used to make being separated of polymerisate that generates by polymeric monomer intermixture to minimize.In addition, organic thinner is normally non-flammable relatively.
The organic thinner of expection comprises the trimethyl carbinol (TBA); Glycol, as ethylene glycol, and polyvalent alcohol, as glycerine.Preferably, organic thinner is fully dissolving in extraction solvent, thereby promotes in extraction step from the solidified goods its removal.Other organic thinners that are fit to are conspicuous for those skilled in the art.
The amount of organic thinner can provide required effect effectively.Usually, thinner accounts for the 5-60 weight % of monomer mixture, and 10-50 weight % is preferred especially.
According to present method,,, make the monomer mixture moulding and the curing that comprise at least a hydrophilic monomer, at least a cationic siliceous random copolymers and the optional organic thinner that exists as static state casting or rotated mold filing by ordinary method.
Use initiator,, under 179 described those conditions,,, can form lens, be incorporated herein this patent as a reference as Diisopropyl azodicarboxylate (AIBN) and peroxide catalyst by radical polymerization as U.S. Patent No. 3,808.The light initiation polymerization of monomer mixture well known in the art also can be used in the method for formation goods of the present invention.Before monomer polymerization, can add tinting material etc.
Then, from the solidified goods, remove the unreacted monomer of q.s and the organic thinner when existing, thereby improve the biocompatibility of goods.When lens are installed, unconverted monomer is discharged into causes in the eyes and stimulate and other problems.With must be different with other monomer mixtures of combustible solvent such as Virahol extraction because the performance of the siloxane random copolymers of novel seasonization disclosed by the invention can use the non-flammable solvent that comprises water to carry out extraction process.
In case formed the biomaterial that forms by the polymeric monomer mixture that contains cationic siliceous random copolymers disclosed by the invention, extract so and prepare them, and packing and final the use.Finish extraction by making the polymeric material contact different time with all kinds of SOLVENTS such as water, the trimethyl carbinol etc.For example, a kind of extracting process is to flood the polymeric material about 3 minutes in water, removes and anhydrates, and floods the polymeric material about 3 minutes then in another part water, removes that part water, handles the polymeric material at water or buffered soln mesohigh then.
After extraction unreacted monomer and any organic thinner, the randomly goods by the whole bag of tricks machine-shaping known in the art, for example RGP lens.Procedure of processing comprises the lathe cut lens surface, lathe cut rims of the lens, polishing rims of the lens or polishing rims of the lens or surface.For wherein lens surface is by the method for lathe cut, present method is particularly advantageous, because when surperficial toughness or when being rubbery state, the processing of lens surface is difficulty especially.
Usually, before from mould, taking out goods, carry out this course of processing.After process operation, lens can be taken out and from mould with its hydration.Selectively, can fabricated product, hydration then after from mould, taking out lens.
Mechanical property and oxygen-permeable: modulus and elongation test are that the aquagel membrane sample is immersed in the BBS; Use Instron (4502 type) instrument to carry out according to ASTM D-1708a method.The suitable size of film sample is gauge length 22mm and width 4.75mm, and sample also has the end that forms dog bone shape, and to allow clamping sample with the clamp of Instron instrument, its thickness is the 200+50 micron.
Oxygen-permeable (being also referred to as Dk) is measured by following operation.As long as can therefrom obtain to be equivalent to the additive method and/or the instrument of the oxygen permeability values of the inventive method can use.The oxygen-permeable of silicone hydrogel is measured (ANSI Z80.20-1998) by polarographic method, use O2 PermeometerModel 201T instrument (Createch, Albany, California USA), it has assembled a probe that contains center annular au cathode and and the silver anode of cathode insulation endways.Only measure on the flat silicone hydrogel film sample of the free of pinholes of trial test and carry out, these samples have three kinds from 150 to 600 microns different center thicknesses.The center thickness of film sample is measured and can be used Rehder ET-1 electronic thickness gauge to measure.Usually, film sample is in the form of annular discs.Film sample and probe be dipped in the bath that average 35 ℃+/-0.2 ° of recycled phosphoric acid salt buffer salt solution (PBS) is housed measure.Before in probe and film sample immersion PBS bath, film sample is placed on to be used on the pre-wetting cathode center of balance PBS, to guarantee between negative electrode and film sample, not having bubble or excessive PBS to exist, with fixed cover film sample is fixed on the probe then, the cathode portion that makes probe is the contact membrane sample only.For the silicone hydrogel film, between probe cathode and film sample, benefit usually with the very thin film of tetrafluoroethylene (Teflon) polymerization for example in the form of annular discs.In the case, poly tetrafluoroethylene is placed on earlier on the pre-wetting negative electrode, and film sample is placed on the poly tetrafluoroethylene then, to guarantee not having bubble or excessive PBS to exist below poly tetrafluoroethylene or film sample.In case gathered take off data, have only facies relationship numerical value (R2) be 0.97 or higher data enter the calculating of Dk value.Each thickness will obtain two Dk take off data that meet the R2 value at least.Use known regression analysis, calculate oxygen-permeable (Dk) by film sample with at least three different thickness.At first immerse in the pure water with the film sample that is not the solution hydration of PBS, and make its balance at least 24 hours, immerse PHB then, and make its balance at least 12 hours any.Testing tool needs cleaned at regular intervals, regularly uses the calibration of RGP standard model.Bound is determined by the storage values (Repository values) of calculating+/-8.8%, this value is at The Oxygen Permeability of Reference Materials by William J.Benjamin etc., OptomVis Sci 7 (12s): formulate in 95 (1997), mode is by reference incorporated its full content into this paper.
| Title material | Storage values | Lower limit | The upper limit |
| Fluoroperm 30 | 26.2 | 24 | 29 |
| Menicon EX | 62.4 | 56 | 66 |
| Quantum II | 92.9 | 85 | 101 |
Unless in addition special declaration or clear explanation in use thinks that all numerals that are used for the application are modified by term " approximately ".
Take off film and at deionization H from glass disc
2Hydration among the O/extraction at least 4 hours changes fresh deionization H over to
2Among the O, 121 ℃ of hot-pressing processing 30min.Analyze the selection feature of cooling film in the ophthalmology material then, list in table 2.Mechanical testing carries out in BBS according to previously described ASTM D-1708a method.Oxygen-permeable is unit record with Dk (or barrer), measures in 35 ℃ of phosphate buffered saline (PBS)s, just as previously discussed, uses the qualified film of three different thickness.
Original claim of presenting and the claim that may revise comprise variation, replace, improve, improve, Equivalent, with the basic equivalent of specific embodiments disclosed herein and instruction, comprise that those are at present unforeseen or do not fully understand and can be by applicant/patentee and content that other people propose.
Claims (9)
1. the cationic random copolymers of formula (I):
Formula (I)
Wherein x is 0 to 1000, and y is 1 to 300, and L is a linking group and each other can be identical or different; X-is with unicharged counter ion at least; N is from 1 to about 300 integer; Each R1 and R2 are hydrogen independently, the C1-C30 alkyl of straight chain or cladodification, C1-C30 fluoroalkyl, the C1-C20 ester group, alkyl oxide, cycloalkyl ethers, cycloalkenyl group ether, aryl ethers, aralkyl ethers contains the group of polyethers, urea groups, amide group, amido replaces or unsubstituted C1-C30 alkoxyl group, replace or unsubstituted C3-C30 cycloalkyl, replace or unsubstituted C3-C30 cycloalkenyl group, replace or unsubstituted C5-C30 aryl, replace or unsubstituted C5-C30 aralkyl, replace or unsubstituted C5-C30 heteroaryl, replace or unsubstituted C3-C30 heterocycle, replace or unsubstituted C4-C30 Heterocyclylalkyl, replace or unsubstituted C6-C30 heteroarylalkyl, fluorine, the C5-C30 fluoro aryl, or hydroxyl and A are polymerisable vinyl segments.
2. random copolymers as claimed in claim 1, wherein X
-Be selected from by C1
-, Br
-And I
-The group that constitutes.
3. the random copolymers that has following formula (II):
Formula (II)
Wherein x is 0 to 100, and y is 1 to 300.
4. monomer mixture that is used to prepare the polymeric biological material, it comprises the random copolymers as claimed in claim 1 and second hydrophilic monomer.
5. monomer mixture as claimed in claim 4, wherein said second hydrophilic monomer is selected from the group that is made of following material: unsaturated carboxylic acid; Methacrylic acid, vinylformic acid; The alcohol that vinylformic acid replaces; Methacrylic acid 2-hydroxyethyl ester, vinylformic acid 2-hydroxyethyl ester; Vinyl lactam; N-vinyl pyrrolidone (NVP); Acrylamide; Methacrylamide, N,N-DMAA; Methacrylic ester; Ethylene glycol dimethacrylate, methyl acrylate, allyl methacrylate(AMA); The wetting ability NSC 11801, hydrophilic amino vinyl formate monomer; With Qin Shui azolactone monomer.
6. monomer mixture as claimed in claim 4, except that described second hydrophilic monomer, it also comprises hydrophobic monomer, prepolymer, thinner, initiator and their mixture.
7. a bio-medical instrument comprises polymeric monomer intermixture, and described polymeric monomer intermixture comprises the random copolymers as claimed in claim 1 and second hydrophilic monomer.
8. method for preparing bio-medical instrument comprises:
The monomer mixture that comprises the random copolymers as claimed in claim 1 and second hydrophilic monomer is provided;
Make described monomer mixture be in polymerization and setting condition so that poly-unit is provided;
From described poly-unit, extract unconverted monomer; With
Pack described poly-unit and with its sterilization.
9. random copolymers as claimed in claim 1, wherein L is selected from urethanum, carbonic ether; carbamate, carboxyl urea groups, alkylsulfonyl; the C1-C30 alkyl of straight chain or cladodification, C1-C30 fluoroalkyl, C1-C20 ester group; alkyl oxide, cycloalkyl ethers, cycloalkenyl group ether; aryl ethers, aralkyl ethers contains the group of polyethers; urea groups, amide group, amido; replace or unsubstituted C1-C30 alkoxyl group; replace or unsubstituted C3-C30 cycloalkyl, replace or unsubstituted C3-C30 cycloalkenyl group, replace or unsubstituted C5-C30 aryl; replace unsubstituted C5-C30 aralkyl; replace or unsubstituted C5-C30 heteroaryl, replace or unsubstituted C3-C30 heterocycle, replace or unsubstituted C4-C30 Heterocyclylalkyl; replace unsubstituted C6-C30 heteroarylalkyl; C5-C30 fluoro aryl, or the alkyl oxide of hydroxyl replacement and their combination.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75663706P | 2006-01-06 | 2006-01-06 | |
| US60/756,637 | 2006-01-06 | ||
| US11/619,211 | 2007-01-03 |
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| Publication Number | Publication Date |
|---|---|
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102348726A (en) * | 2009-03-09 | 2012-02-08 | 日油株式会社 | Silicone monomer |
-
2007
- 2007-01-04 CN CNA2007800019542A patent/CN101365707A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102348726A (en) * | 2009-03-09 | 2012-02-08 | 日油株式会社 | Silicone monomer |
| CN102348726B (en) * | 2009-03-09 | 2013-10-23 | 日油株式会社 | Silicone monomer |
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