CN1258568C

CN1258568C - Polymer composition and its use

Info

Publication number: CN1258568C
Application number: CN 99126157
Authority: CN
Inventors: 赖有进
Original assignee: Bausch and Lomb Inc
Current assignee: Bausch and Lomb Inc
Priority date: 1991-11-05
Filing date: 1999-12-07
Publication date: 2006-06-07
Anticipated expiration: 2012-11-05
Also published as: MX9206377A; CN1074457A; CN1270973A; CN1063764C

Abstract

A novel class of compounds are disclosed which may be used as novel crosslinking agents for acrylic-containing, vinyl-containing and/or styrene-containing hydrophilic monomers to prepare novel UV-curable hydrophilic copolymers suitable for use as biomedical articles, especially contact lenses.

Description

Polymer composition and application thereof

The application submitted, is entitled as the dividing an application of application for a patent for invention of " a kind of ultraviolet solidifiable novel linking agent that is used for copolymerization " on November 5th, 1992, and the application number of original application is 92113763.x.

The present invention relates to a kind of polymer composition and application thereof, described composition comprises at least a monomer that contains vinyl, at least aly contains monomer acrylic or styryl, and formula AaSsVvR ₁The polymkeric substance of linking agent.

In crosslinked polymer system field, initiator and cross-linked composition (linking agent) are added in the monomer mixture before polymerization usually.These linking agents help to form the polymkeric substance of requirement.This outside cross-linking agent can influence the characteristic and the mechanicalness of polymerisate.

Any watery polymkeric substance that contains about 10%-90% water all is referred to as hydrogel, so the change in physical of hydrogel is very big, and depends on its water-content to a great extent.Because hydrogel presents fabulous biological fitness, thereby people have a wide range of interests as various biomedical articles to hydrogel being applied to biomedicine.For example hydrogel can be used as contact lens, intraocular implant, film and other film, barrier film, conduit, oral cavity fender, artificial tooth bedding and padding, tissue substituent, heart valve, intrauterine contraceptive device, ureter restorer etc.Hydrogel is in the ophthalmology field, especially obtaining business success aspect the contact lens making.

With regard to the hydrogel preparation method, the mechanical characteristics that the linking agent influence is relevant with the hydrogel steadiness, for example, modulus and tear strength.Therefore in hydrogel is synthetic, require to introduce special linking agent and make monomer copolymerizable.

At least the known road of people makes contact lens with hydrogel when the US Patent No 3220960 of Wichterle etc., this patent disclosure comprise hydrogel with the hydrated polymer of crosslinked hydroxyalkyl acrylates of corresponding dibasic ester or methacrylic acid ester.More precisely, also be referred to as to gather-poly-(the 2-hydroxyethyl methacrylic ester) of HEMA be as the hydrogel example that contains about 39% (weight) water.Poly--HEMA is the early stage standard material that is fit to do hydrogel contact lens, but because it has the wearing quality of mechanical workout and polishing under dry state.

Usually, will contain the hydrogel of about 40% (weight) water-content, be called the low water content hydrogel such as methylacrylic acid 2-hydroxyl ethyl ester.In general when water-content increased, the perviousness of oxygen also increased thereupon.Contact lens and other biomedical articles require the height ratio oxygen permeability, because eyes rely on the oxygen that is present in ocular surface fully.

The hydrogel known in addition system is to comprise N-vinyl pyrrolidone (NVP) and methacrylic acid ester, methyl methacrylic acid ester (MMA) for example, multipolymer.NVP-MMA hydrogel water-content as the NVP/MMA proportion function alters a great deal.Yet the water-content of commercial interested most of hydrogel from NVP and MMA is 70%-80%.Known already that the hydrogel that comprises N,N-DMAA multipolymer (DMA) had same nature.Usually water content (weight) is called the high water content hydrogel at the hydrogel of this scope.

Usually the low water content hydrogel has the character that is fit to do soft contact lens.The high water content hydrogel presents and has the attrition resistant oxygen permeability of being fit to.Yet the high water content hydrogel is not easy to make stable eyeglass usually.So according to reports eyeglass ratio is easier to wearing and tearing, also damages than being easier in addition.

The oxygen penetrating power of hydrogel water-content and denseness decision eyeglass thereof.From experimentally, be the oxygen permeability of raising contact lens, and make contact lens wear-resisting that hydrogel denseness with respect to reducing has increased water-content.Only in theory eyeglass should have and the same high oxygen permeability of the eyeglass of NVP-MAA system at least, also has similar intensity and mechanical properties with poly--eyeglass that the HEMA hydrogel is made simultaneously.

This just causes development that siloxanes or fluorinated groups are added in the polymeric hydrogel.But regrettably, but siloxanes and other compounds that contain siloxanes are difficult for being made into humidification; Another is fit to do the main characteristic of contact lens.Humidification is important, if because eyeglass can not humidification it just can not keep lubricated, so eyeglass is worn on the eyes uncomfortable.Best contact lens should not only have fabulous oxygen permeability but also should have fabulous tear humidification.

As mentioned above and the similar linking agent of monomer structure of participating in reaction often be added in the monomer mixture.For example usually with two (methyl) acrylate or two (methyl) acrylamide monomer linking agent as (methyl) acrylate/(methyl) acrylamide system.For making the vinyl-type system reaction that contains N-vinyl pyrrolidone or vinyl-acetic ester, adopt for example ethylene type linking agent usually, in addition such as the Tetraglycol 99 divinyl ether.In general vinyl compound is to have vinyl group (CH ₂=CH-) compound, and normally active.People know such group and relatively are easy to polymerization.Acrylic compound is that those contain acrylic acid groups (CH ₂=CRCOX-), and also easy polymeric compounds.

When requiring specific copolymer systems, when this copolymer systems comprised the monomer of methacrylic acid ester simultaneously and contains the monomer of vinyl, having produced relevant these two kinds of reactant monomer types had different reactive problems.The monomer that contains vinyl and methacrylic acid ester normally can not copolymerization.Therefore in order to make vinyl compound, such as N-vinyl pyrrolidone (NVP) and for example methyl methacrylate (MMA) copolymerization, adopt the methylacrylic acid allyl ester to make linking agent, and adding Peroxycaprylic acid t-butyl ester is made the thermal response initiator and is done the photochemical initation agent with benzoin methyl ether (BME).Because the allyl group in the methylacrylic acid allyl ester is not active, so this monomer mixture at first stands the UV irradiation and makes the polymerization of methylacrylic acid ester group, then makes allyl group and NVP polymerization by thermofixation.

In addition, linking agent can be used to impel the polymerization of NVP/ methacrylic acid ester system such as the Tetraglycol 99 divinyl ether; Yet this also requires thermofixation.Such thermofixation meets the requirements not as UV solidifies, because heating can influence the needed character of final product hydrogel unfriendly.The insufficient meeting of thermofixation makes hydrogel not have the character of requirement in addition.

In polymkeric substance synthetic, other known linking agents commonly used are many vinyl, be typically two or the trivinyl monomer, prevailing is dihydroxyl ethylene glycol, triglycol, butyleneglycol, own-1, the 6-glycol, two or three (methyl) acrylate of sulfo-diethylene glycol diacrylate and methacrylic acid ester; The dimethyltrimethylene glycol diacrylate; Analogues such as Viscoat 295; N, N '-dihydroxy ethylene diacrylamine and diisobutylene acid amides: the diallyl compound that resembles Phthalic acid, diallyl ester and cyano group uric acid triallyl in addition in addition; Vinylstyrene; The ethylene glycol bisthioglycolate vinyl ether; With (methyl) acrylate of polyvalent alcohol, such as trolamine, glycerol, tetramethylolmethane, butyleneglycol, mannitol and Sorbitol Powder.In addition, example comprises N, N-methylene radical-two-(methyl) acrylamide, sulfonated Vinylstyrene and divinylsulfone.The equally usefully reaction product of (methyl) hydroxyalkyl acrylate and unsaturated isocyanate, for example reaction product of US Patent No 4954587 disclosed methylacrylic acid 2-hydroxyl ethyl esters and methylacrylic acid isocyanic acid ethyl ester (IEM).

Other known linking agents are U.S. Patent No.s 4,192827 disclosed polyethers two urethane diisobutylene acid esters and those are by polyoxyethylene glycol, polypropylene glycol and polytetramethylene glycol and methylacrylic acid 2-isocyanic acid ethyl ester (IEM) or m-pseudoallyl-N, the linking agent that N-dimethylbenzyl based isocyanate (m-TMI) reaction is obtained, and US Patent No 4486577 and 4605712 described polysiloxane two urethane diisobutylene acid esters.The reaction product of the reaction product of the polyvinyl alcohol that known other linking agents are polyvinyl alcohol, ethoxylation or polyvinyl alcohol copolymerization of ethylene and 0.1-10 mole % isocyanic acid vinyl acetate (resembling IEM or m-TMI).

As mentioned above, it is preferred to compare to thermal curing methods with UV radiation curing hydrogel separately.Yet so far as is known, there is not complete UV solidified vinylformic acid/vinyl or vinylformic acid/vinyl/styrene polymerization objects system.

The present invention expects to comprise that in conjunction with handling to derive from least one contains the monomer of vinyl, the new curable hydrogel of monomer mixture that at least one contains vinylformic acid or styrene monomer and is selected from the linking agent of novel crosslinker with UV radiation individual curing or with UV/ heating.These new cross-linking compounds as the new linking agent of polymkeric substance are suitable for preparing new aquogel polymer, and it can be used to prepare various biomedical elements.The new hydrogel that produces is particularly useful for making contact lens.These new linking agents have general formula (I):

I.AaSsVvR ₁

Wherein

V represents

A represents

S represents

R ₁Be by the alkyl, polyalkylene oxide, poly-(perfluor) alkylene oxide, the end capped polydimethylsiloxane of dialkyl group, fluorinated alkyl or the group modified end capped polydimethylsiloxane of dialkyl group of fluorinated ether that obtain with unsubstituted hydrocarbon that replace;

R ₂-R ₁₀It is respectively the alkyl of a H or 1-5 carbon atom;

Q comprises the organic group with 6-30 carbon atom aromatic hydrocarbons part;

X, Y and Z are respectively O, NH or S;

V is 1 or greater than 1; With

α, S are respectively more than or equal to 0, and α+S 〉=1.

The invention provides the biomedical articles that production can widespread use, for example apparatus, heart valve, vessel surrogate, intrauterine contraceptive device, film and other film, barrier film, conduit, oral cavity fender, artificial tooth bedding and padding and the intraocular device used of contact lens, surgery.

Fig. 1 and Fig. 2 describe when the NVP/DMA composition ratios changes the influence that the modulus to the urethane film produces.

Fig. 3 describes when the NVP/DMA composition ratios changes the influence that the modulus to the end capped polysiloxane of methacrylic acid ester produces.

Note represents arbitrarily methyl substituted such as " (methyl) acrylate " or " (methyl) acrylamide " at this. Therefore methyl (methyl) acrylate comprises methyl acrylate and methylmethacrylate, and N-alkyl (methyl) acrylamide comprises N-alkyl acrylamide and N-alkyl methyl acrylamide.

The present invention relates to that monomer is connected generation and can be used as especially biomedical material, and be particularly useful for the novel crosslinker of the novel copolymers of contact lenses. These crosslinking agents can use with various monomers, and can produce various contact lens materials, such as, the lens material of rigid permeable gas; Soft hydrogel lens material and soft non-aqueous gel lens material.

Although the present invention can be used for many polymeric materials that comprise hydrogel, hydrogel most preferably, but specific polymer can be come by following monomer derived, and it comprises acrylate, acrylamide, methacrylate, Methacrylamide, contain cinnamic monomer, dimethylacrylate and DMAA monomer, the monomer that contains ethernamine, ethylene carbonate/urethane/urea monomer, (methyl) acrylate/comprise prepolymer of (methyl) acrylamide end-blocking of polysiloxanes, polyfluoro is for siloxanes, Polyfluoroether, poly-urethane prepolymer and other compounds.

The hydrogel of silicone-containing of the present invention comprises polymer such as, the polymer of following general formula:

II. E(*D*A*D*G) _a*D*A*A*E′，

III. E(*D*G*D*A) _a*D*G*D*E′or

IV. E(*D*A)a*D*E′

V. EAE′

In the general formula

A represents to be selected from the divalence polymer-based group of general formula VI compound group:

Wherein

R ^sAnd R^s′Expression contains the 1-10 carbon atom and has the not replacement of ehter bond or the low alkyl group that fluorine replaces between carbon atom respectively; With

P represents 400-10,000 molecular weight;

D represents alkyl double-basis, alkyl-cycloalkyl double-basis or the aryl diradicals of 6-30 carbon atom;

G represents to have 1 to 40 carbon atom has the alkyl double-basis of sulfide linkage or amine key, cycloalkyl double-basis, alkyl-cycloalkyl double-basis, cycloalkyl double-basis, aromatics double-basis or alkyl aromatic double-basis at main chain;

★ represents urethane or urea groups bonding

E and E ' represent the polymerisable unsaturated organic group represented with following general formula VII respectively:

Among the formula VII

R ¹¹Expression has the divalent hydrocarbyl of 1-10 carbon atom;

R ¹²Expression-H or-CH ₃Group;

R ¹³Expression-H base or have the alkyl of 1-6 carbon atom, or Base, wherein, Y is O, S or NH, R ¹⁴Expression has the alkyl of 1-12 carbon atom;

X represents Or

Z represents O, S or NH;

Ar represents to have the aryl of 6-30 carbon atom;

M is greater than 1 or equal 1;

A is 1 at least;

W is 0-6

X is 0 or 1;

Y is 0 or 1; With

Z is 0 or 1.

The preferred prepolymer of being considered with the present invention in formula VI and VII range of structures can define with formula VIII:

Among the formula VIII

M is the undersaturated polymerizable moiety of olefinic;

R ^sAnd R ^{S '}Expression has the low alkyl group of the unsubstituted or fluorine replacement that ehter bond is arranged between 1-10 carbon atom and the carbon atom respectively;

U is O or the organic group with urethane, ether, acid amides or other keys;

M and x are greater than 1 or equal 1; With

When x n greater than 1 time is greater than 5, or n is greater than 20 when x is 1.

The also available formula IX of the preferred urethane prepolymer of the present invention represents:

Among the formula IX

R ₁₅Be the vulcabond double-basis of removing behind the isocyanic ester, and isophorone diisocyanate double-basis most preferably;

M and x are greater than 1 or equal 1 integer that be preferably 3 or 4, x=1 and m=3 or 4 are most preferably respectively; With

N is 5 at least, preferably when x is 1 greater than 20, n=30 or bigger most preferably;

The polysiloxane prepolymer of preferred end thiazolinyl is represented with formula X:

Wherein

M is the undersaturated polymerizable moiety of olefinic;

R ^sAnd R ^{S '}It is respectively the low alkyl group that has the 1-10 carbon atom and the unsubstituted or fluorine replacement of ehter bond is arranged between carbon atom;

M is more than or equal to 1;

N is more preferably greater than 5.

The monomer system of hydrogel lens can adopt usually to present in an amount at least sufficient to not dissolve the hydrophilic hydrogel product but be not enough to influence fully the hydrophobic wetting ability monoene of hydrogel and belong to monomer (for example monoene unsaturated monomer) and polyenoid genus (normally diolefinic) monomer (for example can play the unsaturated compound of the polyenoid genus of linking agent effect).As known to those skilled in the art, the wetting ability monoene belongs to the various character that monomeric mixture also can be used to telomerized polymer.

Representational hydrophilic monomer comprise (methyl) but the water-soluble monoesters of vinylformic acid and the alcohol that contains an esterified hydroxy groups and at least one other hydroxyl, such as (methyl) acrylic acid list and poly aklylene glycol monoesters, for example glycol monomethyl (methyl) acrylate, Diethylene Glycol list (methyl) acrylate, propylene glycol list (methyl) acrylate, dipropylene glycol list (methyl) acrylate and other congeners; N-alkyl and N, (methyl) acrylamide that the N-dialkyl group replaces, such as N-methyl (methyl) acrylamide, N, N-dimethyl (methyl) acrylamide etc.; The N-vinyl pyrrolidone that N-V-Pyrol RC and alkyl replace; N-vinyl-N-alkylamide, such as N-vinyl-N-methylacetamide, N-vinyl-N-methyl-methane amide, N-vinyl acetamide, N-vinyl formamide; (methyl) vinylformic acid Racemic glycidol alcohol ester; Unsaturation amine; Alkoxyethyl acrylate, fumarate and composition thereof; And other monomers well known in the art.

New compound of the present invention can be used to crosslinked at least one contain the monomer of vinyl and at least one contains vinylformic acid or cinnamic monomer.Therefore can produce various novel hydrogels, they are processed into subsequently, as medical element and instrument, reparation usefulness element, implant especially contact lens, eyes implant, cornea implant etc.

Preferentially select for use and partly form containing of the new cross-linked composition of the present invention acrylic acid monomer and comprise (methyl) vinylformic acid, (methyl) acrylamide, (methyl) alkyl acrylate, alkyl (methyl) acrylamide, the polysiloxane group alkyl methacrylate, poly-siloxy-alkyl (methyl) acrylamide, (methyl) vinylformic acid fluoroalkane ester, fluoroalkyl (methyl) acrylamide, the monomer of comparative optimization is a methylacrylic acid 2-hydroxyl ethyl ester, glyceryl methacrylate, hydroxyethyl methacrylamide, 2-methacrylamido ethanol N, the N-DMAA, N, N-dimethylmethacryl amide and (methyl) vinylformic acid.Containing acrylic acid monomer in addition can be to have to contain (methyl) acrylate or the end capped prepolymer of (methyl) acrylamide monomer, and preferred prepolymer is can be by the monomer that contains polysiloxane, polyvinyl ether or Polyfluoroether of ester, carbonic ether, carbamate, urea or urethane bond connection.In addition, the polysiloxane unit that contains in the prepolymer of polysiloxane also can contain fluoroalkyl, fluoroether, alkyl oxide monomer or alcohol groups.

The preferred monomer of considering that contains vinyl can comprise vinyl carbonate in the new cross-linked composition, the alkyl vinyl carbonic ether, polysiloxane vinyl carbonic ether, fluoro-alkyl vinyl carbonic ether, polysiloxane group alkyl vinyl carbonic ether, fluoro-alkyl vinyl carbonate monomer and corresponding carbamate and urea monomer, such as ethylene urea, the alkyl ethylene urea, polysiloxane alkyl ethylene urea and fluoro-alkyl vinyl urea monomer, the monomer that contains vinyl of comparative optimization comprises the N-vinyl pyrrolidone, the N-vinyl, the N-methylacetamide, the N-vinyl, the N-methylformamide, the N-vinyl acetamide, N-vinyl formamide and 2-vinyl-4,4-dimethyl-2-oxazoline-5-ketone (VDMO).

In addition, the monomer that contains vinyl can be a prepolymer, its be selected from vinyl carbonate-, carboxylamine ethene ester-and the end capped prepolymer of vinyl urea, and can comprise the monomer that contains polysiloxane, fluoro-alkyl or fluoroether, the monomer of comparative optimization comprises can pass through poly-inferior hydrocarbyl ether or the Polyfluoroether that ether, carbonic ether, carbamate, urea or urethane bond connect.The vinyl prepolymer that preferably contains polysiloxane can comprise alkyl oxide or alcohol.

Most preferred linking agent is a methacrylic acid group ethyl vinyl carbonic ether, methacrylic acid group ethyl vinyl carbamate and methacrylic acid group ethylethylene urea.This outside cross-linking agent can comprise acrylic acid groups and contain styrene group.This linking agent also can comprise the group of vinylformic acid, vinylbenzene and vinyl.Therefore preferred cross-linking agents can be 4-ethenylphenyl vinyl carbonic ether, 4-ethenylphenyl vinyl carbamate or 4-ethenylphenyl vinyl urea more precisely.

Other preferred new hydrogel compositions that add new linking agent in addition comprise linking agent of the present invention, at least one contains the monomer of methacrylic acid ester and poly-urethane-siloxanes and at least one contains the monomer and the N-vinyl pyrrolidone of (methyl) acrylate or (methyl) acrylamide.The monomer that contains poly-urethane-siloxanes in addition comprises the monomer that contains fluoro-alkyl, fluorine ether or alcohol.Preferably (methyl) acrylate is methylacrylic acid alkane ester, methylacrylic acid 2-hydroxyl ethyl ester, glycol methacrylic acid ester, polysiloxane group alkyl methacrylate and methylacrylic acid fluoroalkane ester.Preferably (methyl) acrylamide is a N,N-DMAA.

Preferred polysiloxane group methacrylic ester is 3-iso-butylene acidic group propyl group three (trimethylsiloxy) silane (TRIS).Preferred hydrogel composition also comprises 2-vinyl-4,4-dimethyl-2-oxazoline-5-ketone (VDMO).

The preferred new hydrogel composition of the present invention also comprises the end capped monomer that contains polysiloxane of at least one (methyl) acrylate or (methyl) acrylamide, contains vinyl monomer in addition, it preferably includes carbonic ether, carbamate, with the polysiloxane group alkyl vinyl monomer that contains urea, or contain vinyl carbonic ether, vinyl carbamate or the vinyl urea and the cross-linked composition of carboxylic acid.

The another kind of preferred hydrogel of new cross-linked composition that comprises contains the polysiloxane of the fluorine ether modification of at least one (methyl) acrylate ended, a monomer and a N-vinyl pyrrolidone that contains (methyl) acrylate or (methyl) acrylamide.

In addition, can imagine the new linking agent of the present invention can be used for the contact lens field all know monomer reaction, such as, HEMA system, contain fluoro-alkyl composition, contain siloxanes and do not contain siloxanes composition, contain the composition of urethane and siliceous composition.

As mentioned above, this new linking agent is the new compound of representing with formula I.The synthetic situation of polymkeric substance is the same arbitrarily, new linking agent and required vinylformic acid, and the vinyl reaction, and when needing and to contain the mechanism of cinnamic monomeric reaction unclear fully as yet.Yet the final product polymeric system that produces is compared with all hydrogels of knowing so far, presents fabulous UV curing performance.Therefore the present invention expects to obtain by all polymeric systems that required monomer and new linking agent reaction are made and the method that obtains above-mentioned final polymer product.

The suitable amounts of linking agent only depends on the desired character of the hydrogel of generation, such as rigid.Usually the concentration of linking agent is no more than 20% (weight) of total monomer mixture, and it is about 10% to be preferably about 0.001%-, and it is about 5% most preferably to be about 0.01%-, and all is enough to make the hydrogel of generation to obtain desired character in each case.Usually, the add-on of linking agent can make the macromolecule hydrogel of generation can absorb about 90% (weight) of about 5%-, and preferably about 10%-is about 80%, most preferably is the water of about 20%-about 75%.

The preferred contact lens that comprise the new cross-linked composition of the present invention be no filler, oxygen permeable, hydrolysis-stable, biologically inert with transparent, can be " firmly " or " soft ", have at least about 10 * 10 ^-11Cm ³Cm/Seccm ²The observable oxygen perviousness (DK unit) of mmHg.

Preferred contact lens composition comprises methacrylic acid ester, and such as 2-hydroxyl methacrylic acid ester or methyl methacrylate, the humidification monomer of vinyl-type is such as N-vinyl pyrrolidone and linking agent of the present invention.

Most preferably with comprising urethane prepolymer, polysiloxane group alkyl methacrylate, the hydrogel contact lens that contains siloxanes that the poly-urethane hydrogel composition of the humidification monomer of at least one acrylic type, the humidification monomer of vinyl-type and linking agent of the present invention is made.Urethane prepolymer is the methacrylate based prepolymer of following general formula X I:

Among the formula XI

D represents to remove two cyanate isophorone double-basis behind the isocyanate groups;

G represents to remove the glycol ether double-basis behind the hydroxyl;

★ represents urethane, urea key; With

N=20-50 (when b=1), or n=5-20 (working as b=2-8).

Can adopt US Patent No 3408429 and 3496254 disclosed rotary casting methods and other methods commonly used, the forming polymer that the present invention is obtained such as disclosed compression mould pressing method in US Patent No 4084459 and 4197266 is contact lens.

Term " on the biomedicine use moulded products " or " biomedical element " are meant that material disclosed herein has and are suitable for the physicochemical property that contact for a long time with lived tissue, blood and mucous membrane.Disclosed already biomedical moulded products all requires these character.People knew already that for example blood was easy to and sustains damage rapidly when blood contacts with product surface.Therefore be necessary that the artificial surfaces that will contact used prosthese and element with blood is designed to blood is had antiprothrombin and non-hemolytic matter.

Therefore, the polymkeric substance that makes of linking agent copolymerization of the present invention can be used to improve colloid, with preparation blood vessel, bladder surgical diagnosis apparatus and as disclosed other elements of US Patent No 3563935 (Kliment).Polymkeric substance also can be used for preparation as the disclosed catheter of US Patent No 3566874 (Shephard).These polymkeric substance can be used for making semi-transparent diaphragm, artificial artificial tooth and as disclosed all goods of above-mentioned U.S. Patent No. 3607848 (Stog) that dialysis is used.

In addition, polymkeric substance disclosed herein and multipolymer used water are boiled and/or hot-pressing processing and can not damaging, and therefore can carry out disinfection.Thereby the goods that polymkeric substance disclosed herein and multipolymer make can be used for surgery, wherein will use the goods that adapt with lived tissue and mucous membrane.

The following example only is used for further specifying the present invention, but is not construed as limiting the invention.Umber that this paper is all and percentage ratio all are by weight, and measure viscosity down at 25 ℃, unless specified otherwise is arranged in addition.

Embodiment 1

By methylacrylic acid hydroxyl ethyl ester and chloroformic acid ethene

Ester prepared in reaction linking agent (HEMAVc)

Be equipped with reflux exchanger, mechanical stirrer, thermopair, dropping funnel and efficient N ₂Add 32.5 gram methylacrylic acid 2-hydroxyl ethyl esters, 21.8 gram pyridine and 300 milliliters of chloroforms at the bottom of 500 milliliters of gardens of input unit in the flask.Then this reactant is cooled to be lower than 5 ℃ and add 25.3 gram chloroformic acid vinyl acetate via dropping funnel, during this thing stirred always and remains below under 5 ℃ the temperature.Allow temperature be warmed up to room temperature and continuous the stirring whole night, then reaction mixture is also filtered with dried over mgso then by silicagel column.Obtain 26 grams down except that desolvating in decompression (b.p.74 ℃ at 1mmtorr) and specify products, GC99.2% purity, NMR spectrum confirms that this appointment product has the structure of expection.

Embodiment 2

Mold pressing hydrogel thin film-contain HEMAVc's

The HEMA/NVP composition

Preparation contains 72 parts of methylacrylic acid hydroxyl ethyl esters (HEMA) (it contains 0.17% ethylene glycol dimethacrylate (EGDMA)); L-vinyl-2-pyrrolidone (NVP), 28 parts; Hydroxyethyl methylacrylate chloroformic acid vinyl acetate, 0.08 part; Darocur-1173[EM industry], 20 parts; Composition with 20 parts of hexanols.Said composition is placed on mold pressing between two sheet glass that are coated with silane, and solidified in 2 hours with the UV radiation.After solvent (ethanol) extraction, weightlessness is 14.5%, and this is interpreted as is the weight of hexanol.Film after aquation is handled contains 65% water, and it is fine to show that polymerization gets.

Embodiment 3

The HEMA/NVP composition of no HEMAVc

To contain HEMA/EGDMA/NVP benzoin methylether (the BME)/peroxidation acid tert-butyl ester (TBO) mixture (71.85/0.15/28/0.75/0.1) and at first be exposed to ultraviolet radiation (UV) down 2 hours, heat auxiliary curing 1 hour down at 120 ℃ then, be molded into eyeglass.Then the eyeglass that produces is extracted with ebullient water.The boiling water of extraction is 18%, and the final water content of eyeglass is 56.5%.When the HEMAVc composition of modification and the data of standard composition are compared, there is more NVP to add in the hydrogel of HEMAVc composition of modification as can be seen.The most important thing is modification the HEMAVc composition copolymerization and solidify as long as finish by being exposed under the UV radiation, rather than resemble standard preparation requirement adopt the auxiliary curing mode of heating.

Embodiment 4-8

The HEMA/NVP composition

Following composition 4-8 prepares with the composition that contains 0.15%EGDMA methylacrylic acid hydroxyl ethyl ester and NVP.Said composition is molded into thin slice, and handles with embodiment 2 identical modes.The hydrogel thin film of gained has following character:

Composition	Embodiment
	Embodiment					4	5	6	7 ^*	8
	The % water tension force (g/mm that the character % of HEMA NVP BME TBO Darocur-1173-HEMAVc EGDMA glycerine film can extract²) modulus (g/mm ²) tear strength (g/mm)	72 28 0.0759 0.1007 0.2 - - 20 13.0 55.3 40 23.5 4.4	72 28 - - 0.2 - - - 13.1 56.2 67 25.5 4.4	72 28 - - 0.2 - - 20 12.8 56.7 45 24.1 4.7	72 28 - - 0.2 0.2 - 20 10.7 58.4 26 17.1 3.2	4	5	6	7 ^*	8	72 28 - - - 0.2 20 12.2 54.0 39 28.7 2.1

^*The composition that contains new linking agent

Embodiment 9

Be used to prepare the urethane composition of the hydrogel contact lens that contains urethane

To contain by isophorone diisocyanate, Diethylene Glycol, molecular weight is 3000 the silicone glycol and the urethane prepolymer of methylacrylic acid 2-hydroxyl ethyl ester, 30 parts; 3-methacrylic acid group propyl group three (trimethylsiloxy) silane (TRIS) 30 Fen; NVP40 part; 40 parts of hexanols; The urethane composition that Darocure is 0.2 part radiation curing 3 hours under UV.Under the same conditions the same combination that adds 0.6 part of HEMAVc is solidified.With the film alcohol extraction that produces, the dry processing with water boil and with the buffered saline solution of PH7.4 then makes it saturated then.List the character of the hydrogel thin slice that obtains below:

	No HEMAVc	HEMAVc is arranged
	No HEMAVc	HEMAVc is arranged	The % water % oxygen permeability-DK modulus g/mm that can extract ²	16 25 144 970	10 37 105 430

Embodiment 10

Be applicable to the urethane hydrogel of preparation contact lens

Preparation contains the monomer mixture of following component.

A) 30 parts of urethane prepolymers that obtain by the silicone glycol of isophorone diisocyanate, Diethylene Glycol, molecular weight 3600

B) 30 parts of TRIS

C) 30 parts of NVP

D) 10 parts of DMA

E) 0.1 part of linking agent HEMAVc

F) 0.2 part of Darocure-1173

G) 40 parts of hexanol solvents.

Said composition solidified under the UV radiation formed film in 2 hours, then with film with alcohol extraction, drying, and use water boil, then use the buffer saline of PH7.4 saturated.The modulus value of this hydrogel thin film is 80g/mm ², oxygen permeability is 98 (DK units), water-content is 41%.

Embodiment 11

The urethane hydrogel composition that contains NVP, DMA, VDMO and HEMAVc

Except with 1 part of 2-vinyl-4,4-dimethyl-2-oxazoline-5-ketone (VDMO) replaces outside 3 parts of NVP and the 1 part of DMA, and monomer mixture contains the identical component as embodiment 10 identical weight ratio.Said composition is processed into the hydrogel thin film of embodiment 10.This hydrogel thin film has 110g/mm ²Modulus, oxygen permeability is 90 (DK units), water-content is 40%.

Embodiment 12

The urethane hydrogel lenses of mold pressing

With embodiment 10 and 11 described poly-urethane compositions by filtering in the bottle of pouring cleaning into disposable strainer.Under inert nitrogen atmosphere, the mixture of 60-90 microlitre is annotated in half plasticity mould of cleaning, cover with second half plastic membrane then.Then with the mould compression, and at UV light (4200microwatts/cm ²) solidified 90 minutes down.With mechanical means mould is opened, and be put in the beaker that aqueous ethanolic solution is housed.In 1 hour, from mould, take out eyeglass, used alcohol extraction then 48 hours, and boiled 4 hours with distilled water.The lens that produce are done the check of beauty treatment quality, cytotoxicity and size.Before will on being applied to eyes, estimating by the eyeglass of check, earlier with buffered phosphoric acid salt salt solution thermal sterilization.

Embodiment 13

Clinical evaluation

The poly-urethane eyeglass of embodiment 12 described mold pressings is worn on 6-10 the patient estimates.In each test, will gather (HEMA) contrast and be worn on the eyes with eyeglass, test is worn on the another eyes with eyeglass.After minimum one hour, after best 5 hours or longer time the humidification and the surface deposits of lens are analyzed and researched.The wettable grade scale in surface is 0-4, the no surface deposits of 0 expression, and 4 expressions have many 0.5mm diameters or bigger settling.But the result of composition eyeglass after having worn 5 hours to embodiment 10 is humidification degree 3, and settling is 0.4.To containing the eyeglass of 1 part of VDMO (embodiment 11 compositions), after having worn 4 hours, perform an analysis, be 3.3 but the result shows the humidification degree, the settling grade is 0.7.

Embodiment 14

Contain M ₂ D ₂₅ / TRIS/NVP/HEMAV _c Composition

With 1, two (the 4-iso-butylene acidic group butyl) sily oxide and 1,1,3,3,5,5 of 3-, hexam ethylcyclotrisiloxane makes α with 1: 8.33 molar ratio reaction, ω-two (methacrylic acid group butyl) polysiloxane (M ₂D ₂₅).With 13 parts of M ₂D ₂₅Mix with 47 parts of TRIS, 40 parts of NVP and 0.1 part of HEMAVc,, produce clear solution through shaking.40 parts of hexanols and 0.2 part of Darocure-1173 are added in this mixture.20 parts of hexanols are added in the said composition together with 0.2 part of BME.The composite mold that produces is pressed into sheet glass and under UV light, solidified 2 hours.This film is used water boil 4 hours with solvent (ethanol) extraction whole night, is placed on then in the buffer saline of PH7.4.These films present following character: water-content 23%; Modulus 369g/mm ²Contact angle is 20 degree; Oxygen permeability 114 (DK unit).

Embodiment 15

Contain M ₂ D ₂₅ The composition of/TRIS/NVP/DMA/HemaVc

Except replacing with equivalent DMA (13/47/30/10/0.1) 10 parts of NVP of embodiment 6, the identical component listed as embodiment 11 is housed in vial.With embodiment 14 described methods this reactant is molded into hydrogel thin film.The hydrogel thin film that forms presents following character: water-content 24%; Modulus 146g/mm ²Contact angle is 25 degree; The oxygen dialysis is 113 (DK units).

Embodiment 16

Composition-M relatively ₂ D 25 / NVP/DMA/HemaVc

Except using additional M ₂D ₂₅(60/30/10/0.1) replaces fully outside the TRIS, press the identical weight ratio compositions formulated of embodiment 15.With embodiment 2 described methods the composite mold that produces is pressed into hydrogel thin film.The film modulus that produces is 570g/mm ², its modulus is the M by 13 to 47 weight ratios of containing with the preparation of the method for embodiment 14 ₂D ₂₅With about 1.5 times of the hydrogel thin film modulus of TRIS.

Embodiment 17-22

Prepare six poly-urethane hydrogel thin films that contain following component:

A) be 30 parts of the urethane prepolymers that obtain of 3600 silicone glycol and HEMA by isophorone diisocyanate, Diethylene Glycol, molecular weight;

B) 30 parts of TRIS;

C) 0-40 part NVP

D) 40-0 part DMA (NVP+DMA=40 part)

E) the HEMAVc linking agent of NVP amount 0.3%

F) 40 parts of n-hexanols;

G) 0.2 part of Darocur-1173 (UV initiator).

These compositions are solidified with UV, then extract with alcohol and with the boiling water hydration, obtain the having following character hydrogel thin film product of (water-content and modulus).Fig. 1 describes the film product of embodiment 17-22, and each film has a curve point respectively.

Table 1

Embodiment	17	18	19	20	21	22
Embodiment	17	18	19	20	21	22	NVP/DMA ratio % water modulus result	40/0 35 430	38/2 46 281	35/5 44 150	30/10 41 80	20/20 41 79	0/40 37 63

Fig. 1 shows the relativeness of modulus/mixture.

Embodiment 23-26

With the component of embodiment 17-22 but with the listed different poly-urethane composition of relative umber preparation of table 2.

A) IDS3H and b) TRIS each 34 parts

C) NVP and d) totally 32 parts of DMA;

E) n-hexanol, f) HEMAVc and g) umber of Darocure-1173 is identical with the umber of embodiment 8-13.

By same way as casting and the processing said composition of routine 17-22, its water-content and modulus data are shown in table 2.Fig. 2 has described the film of routine 23-26 gained, and every kind of film is respectively a bit in the drawings.

Table 2

Embodiment	23	24	25	26
Embodiment	23	24	25	26	NVP/DMA ratio water % modulus	32/0 25 610	24/8 26 275	16/16 31 107	0/32 25 87

The relativeness of modulus/mixture is represented with Fig. 2.

Embodiment 27-30

Based on M ₂ The hydrogel thin film of Dx

Prepare the following hydrogel composition that contains siloxanes, and its method with embodiment 17-22 is molded into hydrogel thin film, the component of this hydrogel composition is:

A) 13 parts of M ₂D ₂₅

B) 47 parts of TRIS

C) NVP and d) DMA, totally 40 parts

E) 40 parts of n-hexyl alcohols

F) HEMAVc, 0.3 part of NVP amount

G) 0.2 part of Darocure

Each film product with embodiment 27-30 is described the relativeness of modulus-composition as a curve point with this respectively in Fig. 3.

In the technical field of this paper, those skilled in the art can make many other improvement and variations to the present invention.Thereby people should be understood that in this claim scope, the present invention can be implemented, rather than as this paper specific as described in.

Claims

1. a polymer composition contains a kind of polymkeric substance, and described polymkeric substance contains and at least aly contains the monomer of vinyl, at least a monomer that contains acrylic or styryl, and 0.001-20 weight % has the linking agent of following general formula:

AaSsVvR ₁

In the formula

V represents

A represents

S represents

R ₁Be by the alkyl that obtains with unsubstituted hydrocarbon that replaces, polyalkylene oxide, poly-perfluor alkylene oxide, the end capped polydimethylsiloxane of dialkyl group, with the end capped polydimethylsiloxane of dialkyl group of fluoro-alkyl or fluoroether modification;

R ₂-R ₁₀It is respectively the alkyl of H or 1-5 carbon atom;

Q is the organic group that contains the aromatics part with 6-30 carbon atom;

X, Y and Z are respectively O, NH or S;

V is 1 or greater than 1; With

A, s are respectively more than or equal to 0, a+s=1 or greater than 1.

2. the composition of claim 1, wherein polymkeric substance comprises the monomer that contains acrylic and contains cinnamic monomer.

3. the composition of claim 1, wherein polymkeric substance comprises at least a poly-urethane siloxanyl monomers that contains methacrylic ester, at least aly contains acrylate or methacrylic ester or contain acrylamide or the linking agent of the monomer of Methacrylamide and N-vinyl pyrrolidone and following formula:

AaSsVvR ₁

In the formula

V represents

A represents

S represents

R ₁Be from the alkyl that replaces and unsubstituted hydrocarbon obtains, polyalkylene oxide, poly-perfluor alkylene oxide, the end capped polydimethylsiloxane base of dialkyl group, the end capped polydimethylsiloxane of dialkyl group with fluoro-alkyl or fluoroether modification;

R ₂-R ₁₀It is respectively the alkyl of a H or 1-5 carbon atom;

Q is the organic group that contains the aromatics part with 6-30 carbon atom;

X, Y and Z are respectively O, NH or S;

V is 1 or greater than 1; With

A, s are respectively more than or equal to 0 and a+s=1 or greater than 1.

4. the composition of claim 3, wherein said poly-urethane-siloxanyl monomers also comprises the fluoro-alkyl monomer.

5. the composition of claim 3, wherein said poly-urethane-siloxanyl monomers also comprises the fluoroether monomer.

6. the composition of claim 3, wherein said poly-urethane-siloxanyl monomers also comprises alcohol monomer.

7. the composition of claim 3, the wherein said monomer that contains methacrylic ester is selected from methylacrylic acid alkyl ester, methylacrylic acid 2-hydroxyl ethyl ester, glyceryl methacrylate, polysiloxane group alkyl methacrylate and iso-butylene fluoroalkyl.

8. the composition of claim 3, the wherein said monomer that contains acrylamide is a N,N-DMAA.

9. the composition of claim 7, wherein said polysiloxane group alkyl methacrylate is iso-butylene acidic group propyl group three (trimethylsiloxy) silane.

10. the composition of claim 3, wherein said linking agent is an iso-butylene acidic group ethyl vinyl carbonic ether.

11. the composition of claim 3, wherein said linking agent are iso-butylene acidic group ethyl vinyl carbamates.

12. the composition of claim 3, wherein said linking agent are iso-butylene acidic group ethyl vinyl ureas.

13. the composition of claim 3, wherein said linking agent are 4-ethenylphenyl vinyl carbonic ethers.

14. the composition of claim 3, wherein said linking agent are 4-ethenylphenyl vinyl carbamates.

15. the composition of claim 3, wherein said linking agent are 4-ethenylphenyl vinyl ureas.

16. the composition of claim 3, wherein said composition also comprises 2-vinyl-4,4-dimethyl-2-oxazoline-5-ketone.

17. the composition of claim 3, wherein said composition is an oxygen permeable.

18. the composition of claim 3, wherein said composition can and be heating and curing by ultraviolet radiation.

19. the composition of claim 3, wherein said composition can pass through solidified by ultraviolet ray radiation.

20. the composition of claim 3, wherein said composition is used for making biomedical element.

21. the composition of claim 20, wherein said biomedical element is contact lens.

22. the composition of claim 1, wherein polymkeric substance comprises and at least aly contains acrylate or methacrylic ester end-blocking or contain acrylamide or the monomer of the end capped polysiloxane of Methacrylamide and at least a monomer and at least a linking agent with following formula that contains vinyl:

AaSsVvR ₁

In the formula

V represents

A represents

S represents

R ₁It is polydimethylsiloxane from the alkyl, polyalkylene oxide, poly-perfluor alkylene oxide, the end capped polydimethylsiloxane of dialkyl group, the end capped fluoro-alkyl of dialkyl group or the fluoroether modification that obtain with unsubstituted hydrocarbon that replaces;

R ₂-R ₁₀It is respectively the alkyl of a H or 1-5 carbon atom;

Q is the organic group that contains the aromatics part with 6-30 carbon atom;

X, Y and Z are respectively O, NH or S;

V is 1 or greater than 1; With

A, s are respectively more than or equal to 0 and a+s=1 or greater than 1.

23. the composition of claim 22, the wherein said monomer that contains polysiloxane also comprises at least a monomer that contains fluoro-alkyl.

24. the composition of claim 22, the wherein said monomer that contains polysiloxane also comprises at least a monomer that contains fluoroether.

25. the composition of claim 22, the wherein said monomer that contains polysiloxane also contain at least a monomer that contains alcohol.

26. the composition of claim 22, the monomer that wherein contains methacrylic ester are the methylacrylic acid alkyl esters.

27. the composition of claim 22, the wherein said monomer that contains methacrylic ester are selected from methylacrylic acid fluoroalkyl ester, methylacrylic acid 2-hydroxyl ethyl ester, glyceryl methacrylate and polysiloxane group alkyl methacrylate.

28. the composition of claim 22, the monomer that wherein contains acrylamide is a N,N-DMAA.

29. the composition of claim 22, the monomer that wherein contains methacrylic ester is a methylacrylic acid.

30. the composition of claim 27, wherein said polysiloxane group methacrylic acid ester are iso-butylene acidic group propyl group three (trimethylsiloxy) silane.

31. the composition of claim 22, the wherein said monomer that contains vinyl is the N-vinyl pyrrolidone.

32. the composition of claim 31, the wherein said monomer that contains vinyl is a 2-vinyl-4,4-dimethyl-2-oxazoline-5-ketone.

33. the composition of claim 22, the wherein said monomer that contains vinyl are polysiloxane group alkyl vinyl carbonic ethers.

34. the composition of claim 22, the wherein said monomer that contains vinyl are polysiloxane group alkyl vinyl carbamates.

35. the composition of claim 22, the wherein said monomer that contains vinyl are polysiloxane group alkyl vinyl ureas.

36. the composition of claim 22, the wherein said monomer that contains vinyl are the vinyl carbonic ethers that contains carboxylic acid.

37. the composition of claim 22, the wherein said monomer that contains vinyl is the vinyl carbamate that contains carboxylic acid.

38. the composition of claim 22, the wherein said monomer that contains vinyl are the vinyl ureas that contains carboxylic acid.

39. the composition of claim 22, the wherein said monomer that contains vinyl is the polysiloxane prepolymers that contains vinyl.

40. the composition of claim 39, wherein said polysiloxane prepolymers contains urethane, urea, ester or carbonic acid ester bond.

41. the composition of claim 39, wherein said polysiloxane prepolymers comprise at least a monomer that contains fluoro-alkyl.

42. the composition of claim 39, wherein said polysiloxane prepolymers comprise at least a monomer that contains fluoroether.

43. the composition of claim 39, wherein said polysiloxane prepolymers comprise at least a monomer that contains alcohol.

44. the composition of claim 22, wherein said linking agent are iso-butylene acidic group ethyl vinyl carbonic ethers.

45. the composition of claim 22, wherein said linking agent are iso-butylene acidic group ethyl vinyl carbamates.

46. the composition of claim 22, wherein said linking agent are iso-butylene acidic group ethyl vinyl ureas.

47. the composition of claim 22, wherein said linking agent are 4-vinyl phenyl vinyl carbonic ethers.

48. the composition of claim 22, wherein said linking agent are 4-vinyl phenyl vinyl carbamates.

49. the composition of claim 22, wherein said linking agent are 4-vinyl phenyl vinyl ureas.

50. the composition of claim 22, wherein said polymkeric substance comprise the end capped polysiloxane of methacrylic acid ester, polysiloxane group alkyl methacrylate, N-vinyl pyrrolidone and described linking agent.

51. the composition of claim 50, wherein said polymkeric substance also comprises N,N-DMAA.

52. the composition of claim 50, wherein said polymkeric substance also comprises 2-vinyl-4,4-dimethyl-2-oxazoline-5-ketone.

53. the composition of claim 22, wherein said polymkeric substance also comprises 2-vinyl-4,4-dimethyl-2-oxazoline-5-ketone.

54. the composition of claim 22, the wherein said monomer that contains acrylamide is a N,N-DMAA.

55. the composition of claim 22, wherein said polymkeric substance comprise at least a vinyl carbonic ether or the end capped silicone monomers of vinyl carbamate, at least a polysiloxane group alkyl vinyl carbonic ether or carbamate monomer, N-vinyl pyrrolidone, at least a acrylic acid monomer and the described linking agent of containing.

56. the composition of claim 55, wherein said silicone monomers also comprise at least a fluoro-alkyl monomer.

57. the composition of claim 55, wherein said silicone monomers also comprise at least a fluoroether monomer.

58. the composition of claim 55, wherein said silicone monomers also comprises at least a alcohol monomer.

59. the composition of claim 55, wherein said to contain acrylic acid monomer be N,N-DMAA.

60. the composition of claim 55, wherein said to contain acrylic acid monomer be glyceryl methacrylate.

61. the composition of claim 22, wherein said composition is an oxygen permeable.

62. the composition of claim 22, wherein said composition can and be heating and curing by ultraviolet radiation.

63. the composition of claim 22, wherein said composition solidified by ultraviolet ray radiation.

64. the composition of claim 22, wherein said composition is used for making biomedical element.

65. the composition of claim 22, wherein said biomedical element is contact lens.

66. the composition of claim 1 is used to prepare the application of contact lens.

67. the application of claim 66 is used to make a kind of contact lens that contain ultraviolet solidifiable hydrogel composition, wherein said composition also contains methacrylic acid group ethyl vinyl carbonic ether, N-vinyl pyrrolidone and hydroxyethyl methacrylic ester.

68. the application of claim 66, be used to make a kind of contact lens that contain ultraviolet solidifiable hydrogel composition, wherein said composition also contains N-vinyl pyrrolidone, 2-vinyl-4,4 dimethyl-2-oxazoline-5-ketone, N,N-DMAA and methacrylic acid group ethyl vinyl carbonic ether.

69. the application of claim 66, be used to make a kind of contact lens that contain ultraviolet solidifiable hydrogel composition, wherein said composition also contains 3-iso-butylene acidic group propyl group three (trimethylsiloxy) silane, N-vinyl pyrrolidone and iso-butylene acidic group ethyl vinyl carbonic ether.