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CN1223673A - Amphiphilic, segmented copolymer of controlled morphology and ophthalmic devices including contact lenses made therefrom - Google Patents

Amphiphilic, segmented copolymer of controlled morphology and ophthalmic devices including contact lenses made therefrom Download PDF

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CN1223673A
CN1223673A CN 97195876 CN97195876A CN1223673A CN 1223673 A CN1223673 A CN 1223673A CN 97195876 CN97195876 CN 97195876 CN 97195876 A CN97195876 A CN 97195876A CN 1223673 A CN1223673 A CN 1223673A
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block
multipolymer
group
lens
polymerisate
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T·赫特
D·洛曼
J·霍普肯
刘钦
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Biotherapeutics Co
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Novartis AG
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Abstract

The subject matter of the present invention is an amphiphilic, segmented copolymer of controlled morphology comprising at least one segment having high oxygen permeability, at least one segment having high ion and water permeability, the segments being linked together through a non-hydrolizable bond, and at least one polymerizable unsaturated group; a process for the preparation of the copolymer; to polymeric products obtainable by further polymerizing and optionally cross-linking the amphiphilic segmented copolymer, and to mouldings, especially contact lenses and other ophthalmic devices comprising a polymeric product of the invention. In a specifically preferred embodiment, the present invention relates to a contact lens comprising a polymeric product of the invention which is suited for extended periods of wear.

Description

Have the amphiphilic block copolymer of controlled morphology and comprise Ophthalmoligic instrument by its contact lens that makes
Field of the present invention
The present invention relates to a kind of amphiphilic block copolymer (segmentedcopolymer) with controlled morphology, this multipolymer contains at least one block with high oxygen permeability, at least one has the block of macroion and water permeability, these blocks link together by the key of non-hydrolysable, and this multipolymer contains at least one polymerisable unsaturated group; The invention still further relates to the preparation method of this multipolymer; The polymerisate that can obtain by further polymerization and randomly crosslinked this amphiphilic block copolymer, moulded product particularly contains contact lens and other Ophthalmoligic instruments of polymerization product of the present invention.In a particularly preferred embodiment, the present invention relates to a kind of contact lens that contains polymerisate of the present invention, this contact lens is suitable for wearing the longer time.
Description of Related Art
Being used to prepare the material that contact lens and other be used for the device of ocular environment must " compatible with eye ", promptly must be in duration of contact not perilesional basically ocular tissue and eye fluid.
A requirement compatible with eye of contact lens is that lens must make the oxygen contact cornea that is enough to keep cornea long-term health amount.Contact lens must allow the oxygen of ambient air to arrive cornea, does not obtain oxygen because cornea does not resemble other organizing from blood supply.If do not have the oxygen of q.s to arrive cornea, keratectasia then take place.Long term hypoxia will cause corneal edema, and the angiogenic growth of not expecting is arranged in cornea." soft " contact lens is closely consistent with the shape of eye, so oxygen is not easy to walk around lens.So soft-contact lens must make the diffusion of oxygen scioptics to arrive cornea.
Another of soft-contact lens requirement compatible with eye is that lens can not adhere on the eye securely.Obviously, the human consumer must take out lens at an easy rate to sterilize, to clean or abandon from eye.Yet lens also must be able to move on eyes, so that tears flow between lens and eye.Tears flow between lens and eye and can make chip, remove under the lens and are finally taken out of tear as foreign particles or dead epithelial cell.Therefore, contact lens can not stick on the eye securely, makes lens fully moving in eye be suppressed.
In the daily type soft-contact lens of design, be balance and the consistency of eye and human consumer's comfort requirement, developed the polymkeric substance and the multipolymer of methacrylic acid 2-hydroxyl ethyl ester (HEMA).These hydrophilic polymers can move on eyes well, and provide enough oxygen-permeable for daily type.
Obtained improved oxygen-permeable by the polymkeric substance that contains siloxanes.Yet polysiloxane has typical high lipophilicity.The lipophilicity of polysiloxane has promoted lipoid in the tear and protein adherence on lens, causes bluring, and has hindered the vision that sees through lens.
Desirable hydrophilicity that many trials attempt the hydrophilic polymer that will be formed by monomer such as HEMA has been arranged and combined by the desirable oxygen-permeable that contains the polymkeric substance that siloxanyl monomers forms.For example DE-A-4113292 discloses by the ophthalmic mouldings that polydiorganosiloxane/poly-(ester) carbonate blocks multipolymer makes, and wherein polysiloxane is connected by Si-O-aryl key chemistry with poly-(ester) carbonate blocks.This material it is said to have favorable mechanical stability, flexibility and dimensional stability, and high-biocompatibility, and be easy to make.It is said that it does not also absorb water, and be applicable to preparation disposal type contact lens.Yet this material cannot be crosslinked after preparation.
EP-A-386249 discloses the oxygen-permeable moulded products of being made up of the segmented copolymer of general formula A-B, A-B-A or B-A-B, the 80 weight % or the more monomeric unit that wherein constitute block A contain a kind of alkyl methacrylate, and the 80 weight % or the more monomeric unit that constitute B block contain silicon-polymethacrylate monomeric unit.This moulded products is made without other chemical modification by described segmented copolymer, promptly by multipolymer being dissolved in a kind of solvent, the solution of gained being carried out curtain coating, and then remove solvent wherein.It is said that this moulded products is characterised in that to have high oxygen permeability.If this moulded products is to be 7.3～9.2cal by solubility parameter 1/2Cm -3/2The polymers soln that makes of solvent form, then can produce such structure, wherein segmented copolymer has experienced micron-scale phase separation and has become microcosmic phase A and B, and the phase that wherein contains B (containing the oxygen-permeable material) extends to another surface from a surface of moulded products continuously.Yet in the preparation of these segmented copolymers, the size of relevant controlling block is not to obtain the explanation of " telechelic " multipolymer.The content of water and ion permeability is not disclosed in EP-A-386249.
EP-A-267158 discloses the Ophthalmoligic instrument of the segmented copolymer that contains polysiloxane and polyoxyalkylene oxide unit, and as contact lens and intraocular implant, they possess the favourable combination of desired properties.According to this invention, contact lens is made by segmented copolymer, and this segmented copolymer is that polydimethylsiloxane, vulcabond and the hydroxyethyl methylacrylate by the polyoxyethylene of band edge hydroxyl, band edge hydroxyl makes.But wherein do not spell out the structure and the form of these segmented copolymers, comprise the accurate arrangement of each single block.
EP-A-330615, EP-A-330616, EP-A-330617 and EP-A-330618 disclose has contact lens a lot of useful performances, wettable, oxygen-permeable, that contain segmented copolymer, and these segmented copolymers contain polysiloxane and polyoxyalkylene unit.Yet the single block of each of these segmented copolymers does not possess controlled and definite structure.
JP-A-61-289323 discloses a kind of soft-contact lens of high oxygen permeability, and this contact lens contains aromatic vinyl compound such as polystyrene end blocks, and conjugated diolefin polymer such as polyhutadiene mid-block.These triblock copolymers are not held functional group, and do not possess enough oxygen-permeable.
JP-A-58-058519 discloses a kind of contact lens material that contains multipolymer, this multipolymer contains the silicone resin unit with functional group such as vinyl, have functional group such as allylic polyether units, and the silicone resin unit with the functional group that can react with the functional group of other component.For this polymkeric substance, the structural arrangement of its each single block is also uncertain equally.
US-A-5371147 and US-A-5314961 disclose hydrophilic acrylate's monomer and have had the segmented copolymer of the siliceous type acrylate of hydrophobicity of polymerizable end group.Also disclose star-type polymer except that linear cross-linking products, their inside is hydrophobicity, and externally is wetting ability.These segmented copolymers can not form aqueous favoring and hydrophobic continuous morphology mutually.
US-A-5115056 discloses acrylate or methacrylic ester and other copolymerization of copolymerization monomer of polyoxyalkylene and fluorine-containing or silicon group, and wherein polyoxyalkylene has polymerisable end-vinyl.The single block of each of gained segmented copolymer does not possess clear and definite controlled arrangement.
EP-A-294416, EP-A-290109 and JP-A-02-004225 disclose block and the graft copolymer based on polydimethylsiloxane and poly-(2-alkyl-2-oxazoline).Sulfonate or alkyl halide are mentioned as the polymeric initiator.In sulfonate, tosylate is preferred, although fluoroform sulphonate demonstrates the ratio of better trigger rate and successive polymerization speed in required product synthetic.According to JP-A-2-4225, positively charged ion end group and the polysiloxane reaction that contains sulfydryl or amino.Utilize inherent performance in the organopolysiloxane, polymkeric substance useful as surfactants, cosmetic material, releasing agent, antifogging agent, static inhibitor, defoamer, textile oil, plastic modifier, lustering agent or the lubricant of gained.
WO-A-94/29756 discloses the interpenetrating(polymer)networks of polysiloxane/polycarbonate block copolymer and methyl methacrylate.
JP-A-05-117390 discloses by active end group and NaOH/MeOH are reacted leading-in end hydroxyl on the Zai Ju oxazoline.
About also open by following these people with the content of 2-alkyl-2-oxazoline preparation two and triblock copolymer, Riffle etc. for example, (I.Yilgor, R.S.Ward, J.S.Riffle, ACS polymkeric substance Preprint, 28 (2), 369,1987; J.S.Riffle, I.Yilgor, US-A-4659777 (1987); Q.Liu, J.Bronk, A.Verma, J.Wilson, R.M.Davis, J.S.Riffle, polymkeric substance Preprint, 33 (1), 215 (1992); W.Liu, G.R.Wilson, R.M.Davis, J.Riffle, polymkeric substance 34,3030 (1993); J.S.Riffle, G.Sinai-Zingde, J.M.DeSimone, A.M.Hellstern, D.H.Chen, I.Yilgor, polymkeric substance Preprint, 29 (2), 93 (1988)); Saegusa etc., (T.Saegusa, H.Ikeda, macromole, 6,805, (1973); Y.Chujo, E.Ihara, T.Saegusa, S.Kobayashi, T.Saegusa, macromolecular chemistry, supplementary issue, 12,11 (1985)) and Litt etc. (M.H.Litt, X.Swamikannu, ACS Symp.Ser., 286,231 (1985)).Used the block (T.Saegusa, H.Ikeda is in above-mentioned quoted passage) of polydimethylsiloxane and polyoxyethylated block (S.Kobayashi, M.Kaku, T.Tsutani, T.Saegusa, Pol.Bul., 9,196, (1983)) or polyhutadiene.
But also do not carry out or clearly state end group functionalized of these segmented copolymers.Riffle etc. transform active end group by adding NaOH/MeOH in above-mentioned quoted passage, but do not specify the end group that obtains.Dui Ju oxazoline carries out modification to other author, the leading-in end hydroxyl by add water or sodium bicarbonate aqueous solution under 100 ℃.Then with these hydroxyls and methacrylic acid or acrylate chloride reaction.Also developed the active end group of polymer chain has directly been reacted to obtain the method for vinyl with acrylic or methacrylic acid or its salt or active ester.Kobayashi etc. disclose the reaction of active cation end group and 4-vinyl benzyl alcoholate have been made ethene end group (Y.Shimano, K.Sato, S.Kobayashi, polymer science magazine, A collects, 33,2715 (1995)).By the end capped hydrosilylation that gathers (2-oxazoline) and have the unitary polysiloxane of Si-H of monoene propyl group, also can make graft block copolymer.Equally, use p-nitrophenyl sulfonate as if can obtain causing than increasing faster.
JP-A-2274712/1990 (Hokushin Kogyo K.K.) discloses several reactions of the living polymerization of Zhong Zhi oxazoline.JP-A-04-085335 discloses the reaction of positively charged ion end group and primary, the second month in a season or the reactive tertiary amine formation organopolysiloxane end group of poly-(2-alkyl or aryl-2-oxazoline).
Also can prepare graft copolymer by the cationoid polymerisation on the polyphenylmethyl base silylene of part trifluoromethanesulfonic acidization by THF, 2-methyl-2-oxazoline or poly-IVE; Referring to Y.Hrkach etc., Gov.Rep.Announce.Index (U.S.) 1994,94 (20), digest numbers 455,301,1994.
By the summary of above-mentioned prior art as can be seen, contain oxygen-permeable although there are many documents to relate to, but the copolymer material of hydrophobicity block and permeate water and ionic wetting ability block, these materials it is said and are suitable for preparing Ophthalmoligic instrument, contact lens particularly, but the Ophthalmoligic instrument that relates to the amphiphilic block copolymer preparation with controllable hydrophilic and hydrophobicity block length was not also disclosed in the prior art, because the length controlled of wetting ability and hydrophobicity block, the microcosmic phase morphology of determining of multipolymer just can be provided, and this can cause determine and the reproducible structure of contact lens material.For the lens that are suitable for really wearing the longer time, the back is a bit to realizing its high oxygen permeability and high water and ion permeability, and the suitable mobility on eye is necessary.
Moreover, although some known soft poly-(HEMA) contact lens is verified long the wearing the time of going up to about 6 nights and 7 days can be arranged, but the human consumer still can not be safely and is cosily worn those lens and reach 7 days or the longer time, because its oxygen-permeable deficiency.The lens that wear real (promptly 7 days or longer) for a long time can produce the formation of vascular surface in minimum keratectasia and the cornea.
Summary of the invention
The purpose of this invention is to provide suitable Ophthalmoligic instrument thus, the novel material of soft-contact lens preparation particularly, because its form is controlled, so this bill of material reveals valuable performance, high oxygen permeability particularly, good mobility in eye, high water and ion permeability, relatively low water absorbed dose, machinery flexibility and flexibility, low creep properties, high optical transparency, high hydrolysis and thermostability.And under lower cost, easily and reproducibly make these materials by rapid polymerization.
Another object of the present invention provides a kind of method for preparing these materials.
A further object of the present invention provides mouldings, and the Ophthalmoligic instrument used of vision correction particularly comprises contact lens and contains the biomedical articles of these materials, ophthalmic lens for example, cornea,artificial and film.
Another purpose of the present invention provides a kind of contact lens of wearing of longer time that is suitable for, for example continuously closely with ocular tissue with wear up to 30 days under tear contacts.
Purpose of the present invention can be by realizing astoundingly based on following discovery, promptly at the hydrophobic polymer that is loaded with the initiator group, under the existence of the preferred polymkeric substance that specifies below, pass through hydrophilic monomer, the preferred monomeric controlled fusion that specifies below can " be made " and contain the amphiphilic block copolymer that oxygen-permeable block and water and ion can see through block, perhaps conversely, in the presence of the hydrophilic polymer that is loaded with the initiator group, obtain above-mentioned multipolymer by the controlled fusion of hydrophobic monomer, and in the amphiphilic block copolymer of gained or its end group place, polymerisable unsaturated group can be provided, this will be further polymerization and/or the crosslinked approach of opening up, to obtain the to be advantageously used in preparation Ophthalmoligic instrument, particularly to comprise being suitable for the polymerization product of the longer time wears those contact lens.
Therefore a theme of the present invention is a kind of amphiphilic block copolymer that contains at least one block A and at least one B block, wherein block A contains a kind of oxygen-permeable polymkeric substance (hereinafter referred to as " oxygen-permeable polymkeric substance ", referring to following definition), but B block contains a kind of water and ion perviousness polymkeric substance (hereinafter referred to as " ion permeability polymkeric substance ", referring to following definitions), block A and B are that the key by a non-hydrolysable links together, and wherein multipolymer contains at least one polymerisable unsaturated group.
Employed in disclosure and claims book of the present invention " oxygen-permeable polymkeric substance " is meant the polymerisate that can polymerization forms the polymerizable material with high oxygen permeability polymkeric substance.These materials comprise monomer, oligopolymer, big monomer etc., and their mixture, these materials can with similar or different polymerizable material polymerizations, form the polymkeric substance that oxygen has relative higher rate of diffusion therein.
Similarly, " ion permeability polymkeric substance " is meant the polymerisate that can polymerization forms the polymerizable material with macroion perviousness.These materials comprise monomer, oligopolymer, big monomer etc., and their mixture, these materials can with similar or different polymerizable material polymerizations, form the polymkeric substance that ion or water have higher relatively infiltration rate therein.
Another theme of the present invention is a kind of preparation method of multipolymer as defined above, and this method comprises the steps: a) to be used as in multipolymer and provides at least one can heat or photochemistry activatory positively charged ion or radical initiator group at least one end group of compound of block A or B block or the side group; B) on the initiator group that is present on described block A or the B block, carry out graft polymerization, form B block or block A respectively by this monomeric polymerization with a kind of monomer; C) randomly change monomer and carry out other graft polymerization with a kind of and the monomer that constitutes block A and B identical or different hydrophobicity or hydrophilic monomer, with prepare other hydrophobicity block A ' and/or other wetting ability B block '; And if should provide polymerisable final unsaturated group at the end that increases block; D then) thus obtained segmented copolymer or its appropriate derivative and the functionalized compounds with polymerizable unsaturated group are reacted.
Another theme of the present invention be randomly other vinyl comonomer and randomly contain at least two unsaturated groups linking agent in the presence of, the multipolymer that makes above-mentioned definition is by the available polymerisate of the further polymerization of polymerizable unsaturated group.
A theme more of the present invention is the mouldings that mainly contains the polymerisate of above-mentioned definition.Preferably, this mouldings is the Ophthalmoligic instrument that vision correction is used, particularly contact lens.
A preferred theme of the present invention is to be suitable for longer time and ocular tissue and tear Continuous Contact, compatible with eye transparent lens.A particularly preferred embodiment of the present invention be suitable for safety and comfort ground wear for a long time and need not take out, can wear the vision correction lens of longer time.
The application of the amphiphilic block copolymer that a theme more of the present invention is above-mentioned definition on Ophthalmoligic instrument, particularly contact lens that the preparation vision correction is used, and the polymerisate of described multipolymer or above-mentioned definition is coated with the application that applies at product surface.
Amphiphilic block copolymer contains the block with high oxygen permeability and has the block of macroion and water permeability.It is the controlled length of specific characteristic that these blocks have in this area, for first block as the grafting matrix, the controlled length of block is because of such fact, promptly have the product that the commodity of definite chain length can get or the polymkeric substance of independent preparation and can be used as starting raw material, and for increasing block, its chain length pass through add monomeric amount and polymerizing condition control.According to the present invention, the amphiphilic block copolymer of gained can also be further processed into to having the material with the micron-scale phase separation form of determining of two IPN external phases, described form is present in the non-crosslinked film and crosslinked final product, for example in the contact lens.By hydrophilic and length hydrophobic block, not only can regulate microcell and (for the size of optically transparent material＜150nm), and can controllably regulate the infiltration structure of microfacies, comprise gas, water and ionic passage.Polymerisate that is obtained by amphiphilic block copolymer of the present invention and crosslinked final product (mouldings) have the co-continuous form thus, wherein oxygen-permeable block A provides high oxygen permeability on the whole thickness of mouldings (for example contact lens), this high oxygen permeability is essential for oxygen to the suitable supply of cornea, and the ion permeability B block provides high water and ion permeability, and this high water and ion permeability are essential for the suitable mobility of lens on eye.
In amphiphilic block copolymer of the present invention, wetting ability and hydrophobicity block are that the covalent linkage by non-hydrolysable links together, and this connecting key helps the chemical stability of product.These multipolymers have at least one polymerisable unsaturated group, therefore can randomly carry out polymerization further with other vinyl monomer, perhaps carry out crosslinking reaction further with linking agent.These multipolymers can also have the polymerizable unsaturated group more than, therefore can next carry out effectively directly crosslinking reaction, and quick-setting material is provided.
Can be used for preparing Ophthalmoligic instrument, particularly soft-contact lens according to amphiphilic block copolymer of the present invention.Other indefiniteness Application Areas has biomedical material and implant, ophthalmic lens for example, cornea,artificial and film.They also can be used for the field beyond the Ophthalmoligic instrument, for example use making coatings on optical fiber, are used as the technology film in drug delivery system, and the film, sheet material and the mouldings that are used as various objectives.
In aforesaid all Application Areass, it is favourable using amphiphilic block copolymer of the present invention and the polymerisate by its further polymerization and/or crosslinked gained, this is because they have controlled form, improved performance, higher permanent stability, the reproducibility of raising and less trouble.
Detailed description 1. amphiphilic block copolymers of the present invention
Amphiphilic block copolymer of the present invention contains at least one block A, and this block contains the oxygen-permeable polymkeric substance of following explanation, and promptly oxygen is by its higher relatively polymkeric substance of rate of diffusion.In addition, these materials must be compatible with eye.These oxygen-permeable polymkeric substance include but not limited to polysiloxane, perfluoroalkyl ethers, special unsaturated polymer and polysulfones.These oxygen-permeable polymkeric substance also can contain hydrophilic radical.
According to one embodiment of the invention, the oxygen-permeable polymkeric substance among the block A contains the polysiloxane block with end alkylidene group of logical formula I:
Figure A9719587600171
Wherein n is 5 to 200 integer; Alk is the alkylidene group of 20 carbon atoms at the most; 80～100% radicals R 1, R 2, R 3And R 4Be alkyl independently of each other, 0～20% radicals R 1, R 2, R 3And R 4Be alkenyl, aryl, fluoro-alkyl or cyano group alkyl independently of each other.
In a preferred implication, n is 5 to 120 integer, more preferably 10 to 100, especially 20 to 80.
In a preferred implication, 80～100%, preferred 85～100%, 90～100% radicals R particularly 1, R 2, R 3And R 4Be the low alkyl group of 8 carbon atoms at the most independently of each other, the more preferably low alkyl group of 4 carbon atoms, the low alkyl group of 2 carbon atoms especially at the most at the most.In a further preferred implication, R 1, R 2, R 3And R 4Be methyl.
In a preferred implication, 0～20%, preferred 0～15%, 0～10% radicals R particularly 1, R 2, R 3And R 4Be low-grade alkenyl independently of each other, unsubstituted or low alkyl group-or the phenyl that replaces of lower alkoxy, fluoro low alkyl group such as trifluoro propyl, or cyano-lower alkyl group.
According to another embodiment of the present invention, the oxygen-permeable polymkeric substance among the block A contains the perfluoroalkyl-polyether block of logical formula II:
-(E) k-Z-CF 2-(OCF 2) x-(OCF 2CF 2) y-OCF 2-Z-(E) k(II) wherein x+y is number in 10 to 100 scopes; Each Z is divalent group or key of 12 carbon atoms at the most independently of each other; Each E is alkoxyl group independently of each other, as-(OCH 2CH 2) q-, wherein the statistical average value of q is 0 to 2, connection-Z-E-represents sequence-Z-(OCH 2CH 2) q-; And k is 0 or 1.
Preferably, Z is a key, low-grade alkylidene or-the CONH-arylidene, wherein-CO-part and CF 2Group connects.Particularly preferably, Z is low-grade alkylidene, especially methylene radical.
The perfluoro alkoxy unit OCF that in logical formula II, has index x and y 2And OCF 2CF 2But random distribution.Preferably, the summation of index x+y is the number in 10 to 50 scopes, preferred especially 10 to 30.Preferably, ratio x: y in 0.5 to 1.5 scope, particularly 0.8 to 1.2.
In another embodiment of the present invention, the oxygen-permeable polymkeric substance among the block A contains a kind of unsaturated polymer, and this unsaturated polymer contains and is selected from logical formula III and (IV) unitary repeating unit:
Figure A9719587600181
R wherein 5Be hydrogen, alkyl or trialkylsilkl; R 6Alkyl for unsubstituted or alkoxy, alkoxy carbonyl, hydroxyl, carboxyl, halogen or aryl replacement; The alkenyl unsubstituted or alkoxy, alkoxy carbonyl, carboxyl, halogen or aryl replace; Or alkynyl unsubstituted or that alkoxy, alkoxy carbonyl, carboxyl, halogen or aryl replace; And R 7And R 8Be hydrogen or alkyl independently of each other; Perhaps R 6And R 7Combine and be-(CH 2) p-, wherein p is 3 to 5 integer; Perhaps R 6And R 7Combine and be the residue of divalent of general formula (V):
Figure A9719587600182
Wherein r and s are 1 to 3 integer independently of each other, but are not 1 simultaneously; Perhaps R 7And R 8Combine and be-(CH 2) p-, wherein p as above defines; M and o are 10 to 100000 integer independently of each other; With the summation of m and o be 20 to 100010 integer.
Typically, the unsaturated polymer that contains the repeating unit of logical formula III and/or (IV) contains the residue R as end group 5, R 6, R 7Or R 8
Preferably, residue R in the unit of logical formula III and/or (IV) 5, R 6, R 7And R 8Be chosen such that and promptly make at least 20% unit contain unsaturated C-C.
Preferably, R 5Be the hydrogen or the low alkyl group of 8 carbon atoms at the most, more preferably hydrogen or the low alkyl group of 4 carbon atoms at the most, more preferably hydrogen or the low alkyl group of 2 carbon atoms, particularly hydrogen or methyl at the most.In another preferred implication, R 5Be three low alkyl group silyls, particularly trimethyl silyl, especially work as R 5When linking together with the unit of logical formula IV.
Preferably, R 6Be the low-grade alkenyl of 8 carbon atoms at the most, they are by unsubstituted or replaced by lower alkoxy, elementary alkoxy carbonyl, carboxyl, halogen or phenyl, more preferably, and R 6Be the low-grade alkenyl of 4 carbon atoms at the most, they are by unsubstituted or replaced by lower alkoxy, elementary alkoxy carbonyl, carboxyl, halogen or phenyl, especially, and R 6Be the low-grade alkenyl of 4 carbon atoms at the most, they are by unsubstituted or replaced by halogen or phenyl.
Perhaps, R 6Be preferably the low alkyl group of 8 carbon atoms at the most, they are by unsubstituted or replaced by lower alkoxy, hydroxyl, halogen or phenyl, more preferably, and R 6Be the low alkyl group of 4 carbon atoms at the most, they are by unsubstituted or replaced by lower alkoxy, halogen or phenyl, especially, and R 6Be the low alkyl group of 4 carbon atoms at the most, they are by unsubstituted or replaced by halogen or phenyl.
Preferably, R 7Be the hydrogen or the low alkyl group of 8 carbon atoms at the most, more preferably, R 7Be the hydrogen or the low alkyl group of 4 carbon atoms at the most, further preferably, R 7Be hydrogen or the low alkyl group of 2 carbon atoms, particularly hydrogen or methyl at the most.
Independently, R 8Have and R 7Identical implication and preferred form.
In an embodiment preferred, R 6And R 7Combine and be-(CH 2) p-, wherein p is 3 to 5 integer, preferred 3 or 4, more preferably, R 6And R 7Combine and be trimethylene.
In a preferred implication, R 6And R 7Also can connect together forms the residue of divalent of general formula (V), and wherein preferred r is 1 to 3 integer, and s is preferably 2.
In an embodiment preferred, R 7And R 8Combine and be-(CH 2) p-, wherein p is 3 to 5 integer, preferred 3 or 4.Preferably, R 7And R 8Combine and be trimethylene.
In a preferred implication, m and o are 10 to 100000 integer independently of each other, 20 to 10000 integer more preferably, particularly 25 to 1000.Preferably, the summation of m and o is 20 to 100010, more preferably 20 to 10000, and 25 to 1000 integer particularly.
Preferred unsaturated polymer is for containing the compound that is selected from logical formula III and (IV) unitary repeating unit, wherein R 5, R 7And R 8Be hydrogen, R 6Be low-grade alkenyl or the low-grade alkenyl that replaced by halogen.
Preferred unsaturated polymer is for containing the compound that is selected from logical formula III and (IV) unitary repeating unit, wherein R 5, R 7And R 8Be hydrogen, R 6Be the low-grade alkenyl of 4 carbon atoms at the most.
Preferred unsaturated polymer is the compound that contains the repeating unit of logical formula III, wherein R 5, R 7And R 8Be hydrogen, R 6Be the low-grade alkenyl of 4 carbon atoms at the most.
Preferred unsaturated polymer is the compound that contains the repeating unit of logical formula IV, wherein R 5Be three (low alkyl group) silyl, R 6Be low alkyl group.
Preferred unsaturated polymer is for containing the alternately compound of repeating unit, the wherein R of logical formula III and (IV) 5, R 7And R 8Be hydrogen, R 6Be the low alkyl group or the low-grade alkenyl of 4 carbon atoms at the most.
Unsaturated polymer for example is, can be by the conjugation aliphatic series of halogen or low alkyl group replacement or the polymkeric substance of alicyclic diene, can be by low alkyl group or the alkynes of trimethyl silyl replacement or the polymkeric substance of diine, the multipolymer of conjugated diolefine and wetting ability or hydrophobic vinyl monomers can also be the partially hydrated derivative of above-claimed cpd.
The specific examples of preferred conjugated diolefin polymer be suitable-, anti--, isotaxy-or syndiotaxy-1,2-polyhutadiene, 1 or polyisoprene, poly-pentenamer, sovprene and poly-piperylene.The example of preferred multipolymer is divinyl or isoprene and wetting ability or hydrophobic vinyl monomers, as the multipolymer of vinyl cyanide, vinylbenzene, acrylic or methacrylic acid hydroxyl ethyl ester.The example of polyyne is poly--1-trimethyl silyl-propine.
Particularly preferred unsaturated polymer is selected from syndiotaxy-1,2-polyhutadiene, 1 and polyisoprene.
Particularly preferred unsaturated polymer is poly--1-trimethyl silyl-propine.
Another particularly preferred unsaturated polymer is a 1.
In another embodiment of the present invention, the oxygen-permeable polymkeric substance among the block A contains and comprises at least a general formula VI a) to VI d) the polysulfones of structural unit:
-R-SO 2-?????????????????Ⅵa)
Figure A9719587600211
-R-SO 2-R-O-?????????????Ⅵc)
-R-O-R-SO 2-R-R-SO 2-VI d) wherein the structural unit VI a) in R be alkylidene group or arylidene, at structural unit VI b), VI c) and VI d) in R be arylidene, particularly phenylene.
In one embodiment of the invention, the oxygen-permeable polymkeric substance among the block A can contain a kind of in the above-mentioned polymkeric substance.According to another embodiment, the oxygen-permeable polymkeric substance among the block A can contain more than a kind of above-mentioned polymkeric substance, for example can contain sub-block of perfluorinated alkylidene polyethers or polyhutadiene (a) and the sub-block of polysiloxane (b).
In this case, preferably, the number of the sub-block (b) among the block A is more than or equal to the number of sub-block (a).
Preferably, the ratio of block A neutron block (a) and number (b) is 3: 4,2: 3, and 1: 2 or 1: 1.
Mol ratio between block A neutron block (a) and the number (b) more preferably is 2: 3,1: 2 or 1: 1.
The aforesaid molecular-weight average that contains the block A of sub-block is about 1000-50000, and is preferred about 3000～15000, especially preferred about 5000～12000.
Block A neutron block (a) and sum (b) are preferably 2 to about 11, are preferably 2 especially to about 9, and especially 2 to about 7.Preferably, Zui Xiao block A comprises a sub-block of perfluor (a) and/or a sub-block of siloxanes (b).
In the preferred embodiment of the block A of the composition that preferably has aforementioned proportion, each end of block A is by siloxane blocks (b) end-blocking.
The composition of described divalence block A is always formed corresponding to an average statistics up and down.This means, for example, even comprised the single segmented copolymer group that contains identical repeating unit, specified as long as final statistical average consists of.
Except that at least one contains the block A of oxygen-permeable polymkeric substance, amphiphilic block copolymer of the present invention also contains at least one B block that contains ion permeability polymkeric substance as described below, and promptly the polymkeric substance in this block has higher relatively rate of diffusion during by it at ion.In addition, these materials must be compatible with eye.
B block is made up of hydrophilic monomer, and links to each other with block A by the key of non-hydrolysable.The specific examples that is suitable for the hydrophilic monomer of B block has cyclic imide base ether, vinyl ether, cyclic ether (comprising epoxide, the ring-type unsaturated ethers), aziridine, β-lactone and beta-lactam that N-replaces.Other suitable monomer comprises ketene diacetal, vinyl acetal and phosphorane.
The cyclic imide base ether that can be used as the hydrophilic monomer that is used to constitute B block is the cyclic imide base ether compound of general formula (VII):
Figure A9719587600221
R wherein 9Expression hydrogen atom, 22 carbon atoms and randomly contain the alkyl of ether, ester or urethane groups, hydroxyalkyl or alkenyl, cycloalkyl, aralkyl or aryl at the most; T is 2 or 3.
The specific examples of suitable and preferred cyclic imide base ether is the 2-oxazoline of general formula (VII), wherein R 9Be 10 at the most, more preferably the alkyl of 4 carbon atoms or alkenyl or hydroxyalkyl at the most.Same preferred also have they at the locational methacrylic acid 2-of hydroxyalkyl isocyanide acyl group ethyl ester adducts.If use and on the 2-position, have the 2-oxazoline of alkenyl as hydrophilic monomer, then in the B block (on side chain) of amphiphilic block copolymer, provide polymerisable unsaturated group, they can be used as the required polymerizable unsaturated group of final polymerization, to obtain being suitable for preparing mouldings, the polymerisate of contact lens for example, or as other polymerizable unsaturated group, so that directly crosslinked possibility to be provided in the preparation of mouldings.
The most preferred cyclic imide base ether that is used to prepare B block is 2-Jia oxazolin.
Other compound that is preferably used as hydrophilic monomer in the preparation of B block is the vinyl ether of general formula (VIII):
R 10-O-CH=CH 2(VIII) be R wherein 10Be the alkyl or the alkoxyalkyl of 1～10 carbon atom, dioxolane, the cyclic ether of dioxetane or general formula (IX), (X) or (XI):
Figure A9719587600231
Wherein u is 1 to 3 integer, each R 11Represent hydrogen or 22 carbon atoms and randomly contain the alkyl or the alkenyl of ether, ester or urethane ester group at the most independently, or be cycloalkyl, aralkyl or aryl, R 12Be the alkyl of 4 carbon atoms, alkenyl or alkoxyalkyl at the most.
Most preferred vinyl ether is a methylvinylether, ethyl vinyl ether and methoxy ethyl vinyl ether.
Preferred cyclic ether is the epoxide of general formula (X), one of them R 11Be hydrogen, another R 11Alkyl, particularly oxyethane, propylene oxide and butylene oxide ring for hydrogen or 1 to 4 carbon atom.The same preferred wetting ability glycidyl ether that also has general formula (XI), wherein R 11Be hydrogen, R 12Be methyl, vinyl, allyl group or ethoxyethyl group.
In amphiphilic block copolymer of the present invention, block A and B are that the key by non-hydrolysable links together.Employed term in the context of the invention " key of non-hydrolysable " is meant by common moisture or solvent hydrolysis reaction, for example under acidity or alkaline condition, and the covalent linkage that can not break apart.Here " non-hydrolysable " of indication for example is
Figure A9719587600241
Key.The specific examples of the hydrolyzable bond in above-mentioned this term intended scope has ester bond, amido linkage and urethane bonds.2. the preparation of amphiphilic block copolymer
In amphiphilic block copolymer of the present invention, the key of the non-hydrolysable between block A and the B is achieved in accordance with the invention by following method formation, promptly in the presence of suitable functionalized block A, make a kind of suitable hydrophilic monomer (this monomer constitutes B block) polymerization, make the unitary block of hydrophilic monomer on the functionalized position of block A, increase, or in the presence of suitable functionalized B block, make a kind of suitable hydrophobic monomer (this monomer constitutes block A) polymerization, make the block of hydrophobic monomer units on the functionalized position of B block, increase.
In the context of the present specification, functionalized block is also referred to as " macromole evocating agent ".It is a kind of oxygen-permeable of as above explanation or polymerizable compound of ion permeability polymkeric substance of containing, and for functionalized oxygen-permeable block A, it has end and/or the side group initiator group I of representing as following signal formula:
Figure A9719587600242
Wherein A represents block A, and I represents a kind of initiator group, and v is 0 to 20.
Initiator group I can be can heat or photochemistry activatory cationic initiator group, or can heat or photochemistry activatory radical initiator group.But the specific examples of preferred photochemistry activatory cationic initiator group has trifluoromethanesulfonic acid ester group (O-SO 2-CF 3) ,-I (iodide) ,-O-methylsulfonyl ,-O-tosyl group and-Cl+AgSbF 6Most preferred initiator group is the trifluoromethanesulfonic acid ester group.
The initiator group is connected on the block, (the block A in the above-mentioned signal formula) its form is such on this block, promptly at the end group of this block and form the covalent linkage that has formed a non-hydrolysable between first monomer that increases block (B block in the following signal formula), increase block and in the graft copolymerization of preparation amphiphilic block copolymer, be connected on the initial block.Grafting is meant on preformed polymkeric substance by being positioned at the polymer chain that the locational monomer of end group place or side chain begins to increase other.
Can by rights initiator group I be incorporated in the preformed polymkeric substance, for example by positively charged ion or thermal initiator group be present in initial block on being connected of functional group.Have only a kind of method in back to be suitable for forming side chain initiator group (referring to the c in the above-mentioned signal formula)).Preferred trifluoromethanesulfonic acid ester group for example can pass through end group or side group official energy hydroxyl and activatory trifluoromethanesulfonic acid derivative as (CF 3SO) 2The reaction of O and introducing.
As implied above, in the presence of functionalized block A, the graft polymerization of suitable hydrophilic monomer has formed the amphiphilic block copolymer that following signal formula is represented:
Figure A9719587600251
Thus, amphiphilic block copolymer of the present invention is composed as follows in one embodiment, a block A and a B block (A-B type are promptly only arranged, two blocks), perhaps block A and be connected two B block (B-A-B types at its end group place, three blocks), perhaps has pectination, unshowned end B block in the side chain that wherein several B block are a block A (block A can also further be connected with one or two above-mentioned signal formula c certainly)).
In another embodiment, amphiphilic block copolymer of the present invention can be formed (A-B-A type by a B block and two block A that are connected its end group place, three blocks) maybe can have pectination, the side chain that wherein several block A are a B block (B block can also further have one or two end block A certainly).
Also can in the graft copolymerization process, change monomer,, use hydrophobic monomer then on preformed hydrophobicity block A, hydrophobicity block A ' is connected on the end of the B block for preparing in advance so that for example the first wetting ability B block increases.Also can use different hydrophilic monomers the end of wetting ability B block generate different wetting ability B block '.Also can begin, carry out other embodiment of amphiphilic block copolymer of the present invention by functionalized wetting ability B block.In this manual, block A and A ' and B and B ' are called " block A " and " B block " sometimes respectively simply.
The common number-average molecular weight Mn of polymkeric substance that constitutes initial block A is 500～25000, and is preferred 800～15000, more preferably 1000～8000.The length of one or more B block, A ' or the B ' of graft copolymerization on initial block can easily be controlled by the amount of control monomer that graft copolymerization adds (hydrophilic or hydrophobic).Can control the size and the ratio thereof of block in this way at an easy rate.
May in hydrophobicity and/or wetting ability block, comprise polymerisable unsaturated group by the segmented copolymer that obtains at the suitable wetting ability of grafting on the initial block or hydrophobic monomer, if for example hydrophobicity block A contains a kind of diene polymer such as polyhutadiene or polyisoprene, if or the monomer that is used to constitute the wetting ability block contains a unsaturated terminal chain, for example 2-allyl group-oxazolines.If no polymerisable unsaturated group exists, or if there is such group, then can introduce polymerisable unsaturated group by suitable the be reflected at end or the side group place that for example increase block.For realizing this purpose, can after obtaining suitable chain length, stop increasing the graft copolymerization of block, and for example or by using specific reagent, as hydroxy styrenes, vinyl carbinol, HEMA, propargyl alcohol, allyl amine and propargyl amine, perhaps by use KOH/EtOH or primary amine stay at the end that increases block-OH or-NH-or unsaturated group, will be present in terminated initiator group and carry out end-blocking.Also can in graft copolymerization, use suitable comonomer,, in multipolymer, introduce hydroxyl as 2-hydroxyl-alkyl-oxazolines.Can make hydroxyl or NH-group and the isocyanate reaction that for example has polymerizable unsaturated group then.The preferred example of this difunctional's compound has; particularly preferred methacrylic acid 2-isocyanide acyl group ethyl ester (IEM); and isocyanic acid vinyl ester; the isocyanic acid allyl ester; the acryl isocyanic ester; vinylbenzene isocyanic ester, vinyl benzyl based isocyanate, isocyanic acid propargyl ester and (methyl) acrylic anhydride.
For a specific embodiment, in the mode shown in the following reaction scheme, can obtain amphiphilic block copolymer of the present invention, wherein oxygen-permeable block A and ion permeability B block link together by the key of a non-hydrolysable, and multipolymer contains at least one polymerisable unsaturated group.
Figure A9719587600281
Amphiphilic block copolymer of the present invention can have or solvent-free in the presence of prepare.Use to be the inert solvent basically, the solvent that does not promptly participate in reacting is favourable.The example of The suitable solvent has ether, and as ether or diglyme, halohydrocarbon is as chloroform or methane dioxide, bipolar aprotonic solvent, as acetonitrile, acetone, dimethyl formamide (DMF) or dimethyl sulfoxide (DMSO) (DMSO), hydrocarbon, as toluene or dimethylbenzene, and pyridine or N-methylmorpholine.Based on the solvability of block A with the comonomer that forms B block, the mixture that uses these solvents is particularly advantageous.
In the preparation of amphiphilic block copolymer of the present invention, temperature of reaction can for example be-60～150 ℃, preferred 0～80 ℃.Reaction times is about 15 minutes to 7 days, preferred about 2 to 48 hours.If need, reaction can be carried out under argon gas or nitrogen protection gas.
In the terminal group functional reaction that forms urethanum, advantageously add suitable catalyzer, as dibutyl tin dilaurate (DBTDL).3. polymerisate
The invention still further relates to a kind of polymerisate, it can be by at least a aforesaid amphiphilic block copolymer, and if needs the further polymerization of at least a vinyl comonomer (a) and/or crosslinked obtaining.
In preferred polymerisate, based on total polymerisate, the part by weight of amphiphilic block copolymer is 100～50%, particularly 100～80%, be preferably 100～90%.
Polymerisate can need not add comonomer in the presence of suitable initiator, directly further heat by amphiphilic block copolymer or photochemical polymerization or crosslinking reaction make.That is to say that preferred polymerisate has the copolymerization product of the amphiphilic block copolymer of at least two crosslinkable groups separately for one or more.
Perhaps, can realize crosslinked as many unsaturated comonomers (b) by adding comonomer (a) and/or a kind of linking agent.Perhaps aforesaid diblock, three blocks and/or comb copolymer be further polymerization and crosslinked also.
In a preferred polymerisate, there is not comonomer (a), product is for only containing the homopolymer or the polymer network of amphiphilic block copolymer.
The comonomer (a) that is present in the polymerisate can be hydrophilic or hydrophobic, or their mixture.The comonomer of particularly suitable is generally used for preparing the monomer of contact lens and biomedical material for those.
Hydrophobic comonomer (a) is meant such monomer, promptly typically, the homopolymer water fast that they form, and the absorbable water yield is less than 10 weight %.
Similarly, hydrophilic polymerized monomer (a) is meant such monomer, and promptly typically, the homopolymer that they form is solvable in water, or the absorbable water yield is at least 10 weight %.
Suitable hydrophobic comonomer (a) has, but not exhaustively is the C of vinylformic acid and methacrylic acid 1～C 18Alkyl ester and C 3～C 18Cycloalkyl ester, C 3～C 18Alkyl acrylamide and-Methacrylamide, vinyl cyanide, methacrylonitrile, C 1～C 18Chain acid vinyl ester, C 2～C 18Alkene, C 2～C 18Halogenated olefine, vinylbenzene, (low alkyl group) vinylbenzene, C 4～C 12Alkyl vinyl ether, the C of vinylformic acid and methacrylic acid 2～C 10Perfluoroalkyl ester, and corresponding part fluoric acrylate and methacrylic ester, the C of vinylformic acid and methacrylic acid 3-C 12Perfluor alkyl ethide thio-carbonyl-amino ethyl ester, acryloxy and methacryloxy alkylsiloxane, N-vinylcarbazole, the C of toxilic acid, fumaric acid, methylene-succinic acid, methylfumaric acid etc. 1～C 12Alkyl ester.Preference such as vinyl cyanide, the ethene with 3 to 5 carbon atoms belongs to the C of unsaturated carboxylic acid 1～C 4Alkyl ester and perfluoroalkyl and siloxanes alkyl ester, or the vinyl acetate of the carboxylic acid of 5 carbon atoms at the most.
The example of suitable hydrophobic comonomer (a) is a methyl acrylate, ethyl propenoate, propyl acrylate, isopropyl acrylate, cyclohexyl acrylate, 2-EHA, methyl methacrylate, Jia Jibingxisuanyizhi, propyl methacrylate, butyl acrylate, vinyl acetate, propionate, vinyl butyrate, the valeric acid vinyl acetate, vinylbenzene, chloroprene, vinylchlorid, vinylidene chloride, vinyl cyanide, 1-butylene, divinyl, methacrylonitrile, Vinyl toluene, EVE, methacrylic acid perfluoro hexyl ethylenebis dithiocarbamate carbonylamino ethyl ester, isobornyl methacrylate, trifluoroethyl methacrylate, methacrylic acid hexafluoro isopropyl ester, methacrylic acid hexafluoro butyl ester, methacrylic acid three-trimethylsiloxy silyl propyl diester (TRIS) and 3-methacryloxypropyl pentamethyl disiloxane (DSPMA).
The preferred example of hydrophobic comonomer (a) is a methyl methacrylate, TRIS and vinyl cyanide.
Suitable hydrophilic polymerized monomer (a) has, but not exhaustively be, the lower alkyl esters that the hydroxyl of vinylformic acid and methacrylic acid replaces, acrylamide, Methacrylamide, (low alkyl group) acrylamide and-Methacrylamide, N, N-dialkyl group acrylamide, the acrylate of ethoxylation and methacrylic ester, polyoxyethylene glycol-list (methyl) acrylate and polyoxyethylene glycol-monomethyl ether-(methyl) acrylate, (low alkyl group) acrylamide that hydroxyl replaces and-Methacrylamide, the low alkyl group vinyl ether that hydroxyl replaces, sodium vinyl sulfonate, Sodium styrene sulfonate, 2-acrylamido-2-methyl propane sulfonic acid, the N-vinyl pyrrole, N-vinyl-2-Pyrrolidone, 2-Yi Xi oxazolin, 2-vinyl-4,4 '-Er Wan oxazolin-5-ketone, 2-and 4-vinylpridine, the ethene that has 3 to 5 carbon atoms altogether belongs to unsaturated carboxylic acid, amino (low alkyl group)-(wherein term " amino " also comprises quaternary ammonium), single (low-grade alkyl amino) (low alkyl group) and two (low-grade alkyl amino) (low alkyl group) acrylate and methacrylic ester, vinyl carbinol etc.Preference such as N-vinyl-2-Pyrrolidone, acrylamide, Methacrylamide, the lower alkyl esters that the hydroxyl of vinylformic acid and methacrylic acid replaces, (low alkyl group) acrylamide that hydroxyl replaces and-Methacrylamide, and the ethene that has 3 to 5 carbon atoms altogether belongs to unsaturated carboxylic acid.
The example of suitable hydrophilic polymerized monomer (a) is hydroxyethyl methylacrylate (HEMA), Hydroxyethyl acrylate, Propylene glycol monoacrylate, methacrylic acid 3-trimethyl ammonium chloride-2-hydroxypropyl acrylate (Blemer, QA, for example obtain) by Nippon Oil, dimethylaminoethyl methacrylate (DMAEMA), dimethylaminoethyl Methacrylamide, acrylamide, Methacrylamide, N,N-DMAA (DMA), vinyl carbinol, vinyl pyridine, glyceral methacrylate, N-1,1-dimethyl-3-oxo butyl acrylamide, N-vinyl-2-Pyrrolidone (NVP), vinylformic acid and methacrylic acid etc.
Preferred hydrophilic polymerized monomer (a) is a methacrylic acid 2-hydroxyl ethyl ester, dimethylaminoethyl methacrylate, methacrylic acid trimethyl ammonium chloride-2-hydroxypropyl acrylate, N,N-DMAA and N-vinyl-2-Pyrrolidone.
If need, can strengthen polymer network by adding a kind of linking agent such as many unsaturated comonomers (b).In this case, used the term cross-linked polymer.Therefore the invention still further relates to a kind of crosslinked polymerisate, it contains amphiphilic block copolymer, if the words and at least a vinyl comonomer (a) and the polymerization of at least a linking agent (b) and the product of crosslinking reaction that need.
The example of typical linking agent (b) is (methyl) allyl acrylate, two (methyl) vinylformic acid low-grade alkylidene diol ester, two (methyl) vinylformic acid many (low-grade alkylidene) diol ester, two (methyl) vinylformic acid low-grade alkylidene ester, divinyl ether, divinylsulfone, two and trivinylbenzene, three (methyl) vinylformic acid trihydroxymethylpropanyl ester, four (methyl) vinylformic acid pentaerythritol ester, two (methyl) vinylformic acid dihydroxyphenyl propane ester, methylene-bis (methyl) acrylamide, triallyl phthalic ester and Phthalic acid, diallyl ester, α, ω-two (methacryloxy alkyl)-oligosiloxane, as two (methacryloxypropyl) tetramethyl disiloxane, and perfluoroalkyl-or perfluoroalkyl ethers-two (methyl) acrylate.
The consumption of linking agent (b) is to account for the proportional meter of total polymer weight, and its amount is 20～0.05%, and particularly 10～0.1%, preferred 5～0.1%.
Polymerisate is by polyreaction well known to those skilled in the art, by corresponding monomer (term monomer also comprises amphiphilic block copolymer here) with known mode synthetic itself.Normally above-mentioned monomer mixture heating and adding free radical are formed agent.The example that this type free base forms agent has Diisopropyl azodicarboxylate (AIBN), Potassium Persulphate, dibenzoyl peroxide, hydrogen peroxide and SPC-D.If for example heat these compounds, then form free radical by homolysis, can cause for example polyreaction then.
Particularly preferably, polyreaction can be carried out with light trigger.In this case, used the term photopolymerization.In photopolymerization, suitable is to add can cause radical polymerization and/or crosslinked light trigger by light.The example of light trigger is known to those skilled in the art; Especially, the example of suitable light trigger is a benzoin methylether, 1-hydroxycyclohexylphenylketone, Darocure and Irgacure product, preferred Darocure1173 And Irgacure2959 Same suitable reactive photoinitiators in addition, it can for example be introduced in the big monomer, maybe can be used as special comonomer (a).Their example provides in EP632329.Can pass through actinic radiation then, light for example, the UV-light that particularly has suitable wavelength causes photopolymerization reaction.If need, can suitably control the spectrum needs by adding suitable photosensitizers.
Polymerization can have or solvent-free in the presence of carry out.The suitable solvent is the used monomeric solvents of all solubilized in principle, and for example water is pure as low-level chain triacontanol, for example ethanol or methyl alcohol also have carboxylic acid amides such as dimethyl formamide, dipolar aprotonic solvent such as dimethyl sulfoxide (DMSO) or methylethylketone, ketone such as acetone or pimelinketone, hydrocarbon such as toluene, ether such as THF, glycol dimethyl ether Huo diox, halohydrocarbon such as trichloroethane, and the mixture of suitable solvent, as the mixture of water and a kind of alcohol, for example water/ethanol or water/carbinol mixture.4. final product
Can known mode own polymerisate or crosslinking polymerization product be made moulded product, particularly make contact lens, for example in a contact lens mould that suits, carry out the photopolymerization or the photo-crosslinking of polymerisate.Therefore the present invention also further relates to the moulded product that mainly contains novel polymeric product or crosslinking polymerization product.Except that contact lens, other example of moulded product has biomedical articles or particularly ophthalmology moulded product, cornea,artificial for example, ophthalmic lens, the eye bandage is used for the moulded product of surgery, as heart valve and artificial artery, other coating in addition, film or film, for example diffusion control film, but the film that is used for the photo structureization of information storage, or the photoresist material material, as be used for the film or the moulded product of resist or silk screen printing resist, also have granular product, particle product particularly, capsule, particularly microcapsule are used for the film and the plaster of drug delivery system.
A specific embodiments of the present invention relates to and mainly contains polymerisate or the crosslinking polymerization product that comprises amphiphilic block copolymer of the present invention, or by its contact lens of forming.This contact lens has many unusual and very favorable performances.These performances for example have, and with the superior compatibility of human cornea (if the words that need are after suitable surface treatment (coating)) and tear, this performance is based on the balanced proportions of water content, oxygen-permeable and machinery and absorption property.This causes high-comfort and does not cause stimulating and anaphylaxis.Because it is to various salt, nutrient, water and various other tear component and gas (CO 2And O 2) having good through performance, the natural metabolism process in the contact lens corneal of the present invention does not have influence or does not have influence substantially.With many other contain siloxanes or contain the contact lens of perfluoroalkyl different, contain the sucker effect that amphiphilic block copolymer of the present invention is not expected as the contact lens of main component.And this contact lens has high-dimensional stability and shelf lives.
The present invention also further relates to the contact lens that mainly contains a kind of polymerisate of the present invention or crosslinking polymerization product, and they are aqueous soft-contact lens and intraocular implant.
The present invention also further relates to the contact lens that mainly contains a kind of polymerisate of the present invention or crosslinking polymerization product, and they are contact lens and intraocular implants low water content, deflection, gas permeable (RGP).
The favourable part of above-mentioned all is not only applicable to contact lens, and is applicable to other mouldings of the present invention.
The present invention also further relates to the new big monomer of above-mentioned general formula and above-mentioned by the application as matrix coating of its polymerisate that makes or crosslinking polymerization product, matrix for example is glass, pottery or metal, preferred polymers matrix, spendable goods in the ophthalmology for example, as contact lens, ophthalmic lens or eye bandage, and medically spendable goods, as in surgery or medical system, (ophthalmic applications) preferred hydrophilic coating in a kind of situation in back.
Polymerisate also is suitable for and does cornea implant or cornea,artificial, and cell growth substrate, as the material of fixing and cultivate zooblast in vitro and in vivo, as medical implant, as implantable semipermeable membrane material, as artificial barrier film, as the anatomic implants of cosmetic surgery, as the material of repair of cartilage and replacement, as containing the implant that hormone discharges cell, as the islet of Langerhans cell, as breast implant or as artificial joint.
The present invention also further relates to the cornea implant that is made by above-mentioned polymerisate.Can be according to preparing such cornea implant with the above-mentioned identical method of contact lens for preparing.Can use common surgical method to implant cornea implant, for example under the epithelium of cornea, or therein or by it, or the matrix that enters cornea, or enter other organized layer of cornea.This implant can improve the optical property of cornea, for example proofreaies and correct vision deviation, and/or improves the outward appearance of eyes, for example the color of pupil.Cornea implant can cover the zone on the optical axis, and this zone has covered pupil when implanting, and the ability of seeing object is provided, and this implant also covers the optical axis neighboring area.Implant has same visual performance in whole zone.
Have now found that, be responsible for passing through cornea implant, particularly between epithelial cell and stroma cell and even at the high molecular weight component of interior subcutaneous transportation essential metal ionic tissue juice, as protein or glycoprotein, for example somatomedin, peptide, hormone or proteinic to flow for the survival of tissue and the energy for growth that is organized in inside and outside the cornea implant be very important.Therefore the cornea implant that preferably makes will have enough porositys, make that being included in molecular weight can pass through greater than the solute in the 10000 daltonian physiological liquids, here except guaranteeing low-molecular-weight nutrition composition such as glucose, lipoid or amino acid or the flowing of the intercellular breathing gas of implant both sides, also will guaranteeing flowing of tissue juice component.
The porosity of cornea implant or given by the polymer materials of producing it, perhaps hole can be incorporated in the new polymkeric substance by a kind of of many known methods in addition, these known method for example are disclosed in WO90/07575, WO91/07687, US5244799, US5238613 is among US4799931 and the US5213721.
No matter use which kind of method to form the necessary porosity of new implant, the porosity of preferred implant to be enough to make molecular weight up to or pass through greater than 10000 daltonian protein and other biomacromolecule, for example molecular weight is 10000～1000000 dalton, but porosity be unlikely to greatly to make whole cell can by and infiltrate through zone on the implant optical axis.When establishing the porosity of implant by hole, many holes should be contained in the zone on the optical axis, and its quantity is not limited, but but should be enough to make the inside and outside interregional unrestricted flow of structural constituent at implant.
Preferably, the hole on the optical axis zone can not produce and cause go wrong visible scattering of light on the degree of vision correction.Employed term hole is meant such hole before and after this, and promptly it does not have the restriction of geometrical shape, and on the form or rule or irregular.The statement in aperture is not meant that all holes all have identical diameter, and to be interpreted as be mean diameter.
Zone beyond the optical axis, cornea implant have with zone on optical axis in identical porosity.The neighboring area that is centered around the implant in optical axis zone is also referred to as the edge section.Different with the optical axis zone, it can make the corneal cell growth, and implant is fixed on the eye.
The porosity of edge section is an independent characteristic of the material of preparation edge section.If the edge section by with optical axis on the material identical materials make, then on the one hand can on optical axis, introduce hole on the other hand in the edge section with different diameter.On the other hand, the edge section also can be made by another material that is different from the material on the optical axis, and in this case, as mentioned above, the porosity of edge section should be greater than the porosity on the optical axis.Preferably, optical clear polymkeric substance like the polymer phase is contained on a kind of and the optical axis in the edge section; Yet it is not optically transparent material that the edge section also can be contained a kind of, or by a kind of be not that optically transparent porous material makes.
Polymerisate of the present invention or crosslinking polymerization product can support and histocyte, as the life that moves of the cell that forms in vascular endotheliocyte, fibrocyte or the bone; Bonding and the cell growth with irritation cell of special surface properties not necessarily will be arranged.This is favourable, because this method can make cost keep lower.On the other hand, can carry out surface modification to polymerisate by known method, for example the surface plasma by radio frequency glow discharge is handled, as is disclosed among US4919659 and the WO89/00220, perhaps by radiation, chemical treatment or pass through the photochemistry surface grafting.
Can on the surface of polymerisate of the present invention or crosslinking polymerization product, apply one or more components, for example to promote the growth of tissue.This class examples of material is a fibronectin, chondroitin sulfate, collagen, laminine, CAP matter, cold-insoluble globulin, chondronectin, Urogastron, meat fiber albumen, and/or derivative, active part and composition thereof.Particularly suitable be fibronectin, Urogastron and/or derivative, active part and composition thereof.If need, also can after above-mentioned surface modification, carry out such surface applied.Advantageously, new polymkeric substance can for example have good biological stability and anti-sedimentary cell attachment in conjunction with many described performances.
The mechanical property of polymerisate of the present invention or crosslinking polymerization product is applicable to as cornea implant, and preferably, the modulus of this material is 0.5～10MPa.Modulus in described scope makes cornea implant have suitable flexibility, so that it can be embedded in the eye, for example on the zone of Bowman film.
Polymerisate of the present invention or crosslinking polymerization product also can be used as cell growth substrate, for example as cell culture apparatus, as vessel, bottle dish etc., and can be used for bio-reactor, for example in the preparation of valuable protein and other cell cultures component.5. wear longer contact lens of time
The very important one side content of the present invention relates to contain the contact lens of amphiphilic block copolymer of the present invention, because the premium properties of multipolymer, comprise high oxygen transmission rate, the good movability in eye and macroion and water permeability, so it can be used for wearing the longer time, as up to 30 days.
" oxygen transmission rate " of lens used herein is meant that oxygen sees through the speed of a specific ophthalmic lens.Oxygen transmission rate, Dk/t is unit representation usually with barrers/mm, and wherein t is the mean thickness (unit is mm) of the material on the measured zone, and " barrer " is defined as:
[(cm 3Oxygen) (mm)/(cm 2) (second) (mmHg)] * 10 -9
" oxygen-permeable " of lens material, Dk does not rely on the thickness of lens.Oxygen-permeable is the speed that oxygen sees through a kind of material.Oxygen-permeable is unit representation with barrers usually, and wherein " barrer " is defined as:
[(cm 3Oxygen) (mm)/(cm 2) (second) (mmHg)] * 10 -10These are the units that are generally used for this technical field.Therefore, for consistent with the use of this technical field, unit " barrer " will have above-mentioned implication.For example, the Dk of lens is 90barrers (" oxygen-permeable barrer "), and thickness is 90 microns (0.090mm), and then its Dk/t is 100barrers/mm (" oxygen transmission rate barrers "/mm).
The oxygen transmission rate from the outside surface to the internal surface of the lens that the time of wearing is longer must be enough to prevent any substantial keratectasia worn in the time longer.People know, close in the process that the sleep when closing spends the night, because the anoxic cornea approximately expands 3% to 4% at eyelid.People also know, wear common contact lens about 8 hours (spend the night and wear) and will cause keratectasia about 11%.Yet the acceptable contact lens of wearing for a long time will make keratectasia less than about 8% after wearing about 24 hours, and comprising the normal length of one's sleep, be more preferably less than about 6%, most preferably less than about 4%.The preferred contact lens of wearing for a long time will make keratectasia less than about 10% after wearing about 7 days, and comprising the normal length of one's sleep, be more preferably less than about 7%, most preferably less than about 5%.Therefore, the lens that can wear for a long time must have the oxygen-permeable polymkeric substance of q.s, with oxygenous diffusion, reach above-mentioned performance about keratectasia.Preferably, the lens that can wear for a long time have the external phase of oxygen-permeable polymkeric substance from outside surface to the internal surface of lens.
The oxygen-permeable of available following technical measurement lens and the oxygen transmission rate of lens material.Use the Dk1000 tester (by Applied Design and Development Co., Norcross, Georgia obtains) or similar analytical instrument, in a wet cell (being that air-flow is maintained at about 100% relative humidity) in 34 ℃ of flows (J) of measuring oxygen.The airflow that makes and have known oxygen percentage composition (for example 21%) is with about 10～20cm 3One side of the speed scioptics of/min makes nitrogen gas stream with about 10～20cm simultaneously 3The opposite side of the speed scioptics of/min.Measure normal atmosphere P around this system Observed valueWith Mitotoya micrometer VL-50 or similar instrument, by about 10 points are tested, measure the thickness (t) of the lens that are exposed to test zone, and test value is averaged.Measure the concentration of oxygen in nitrogen gas stream (being the oxygen of scioptics diffusion) with DK 1000 testers.The oxygen-permeable D of lens material kDetermine by following formula:
D k=Jt (P Oxygen) J=oxygen flow [microlitre O wherein 2/ cm 2-minute] P Oxygen=(P Observed value-P Water vapour) * (%O 2, in airflow) and [mmHg]
The dividing potential drop P of=oxygen in airflow Observed value=normal atmosphere [mmHg] P Water vapour=0mmHg is in 34 ℃ of (in an exsiccant cell) [mmHg] P Water vapour=40mmHg, the mean thickness [mm] of the lens on the test zone that 34 ℃ of (in a cell that wets) [mmHg] t=expose is D wherein kWith barrers is unit representation, promptly [(cc oxygen) (mm)/cm 2] * [second/mmHg] * 10 -10
Oxygen transmission rate (the D of material k/ t) by oxygen-permeable (D k) obtain divided by the mean thickness (t) of lens.
Oxygen transmission rate (the D of the lens that can wear for more time of the present invention k/ t) be preferably 70barrers/mm at least, more preferably 75barrers/mm at least, most preferably 87barrers/mm at least.Typically, the central thickness of lens preferred about 30～200 microns, more preferably from about 40～150 microns, more preferably about 50～120 microns, most preferably is about 60～100 microns greater than about 30 microns.Form
A requirement of lens material is that outside surface to the internal surface lens from lens should have high transmission of visible light.Comprise the big lens form that is separated the zone and will reduce visible light transmittance, and the image distortion that causes in fact not expected, the value of lens damaged thus as the vision correction device.Therefore, the form of lens must guarantee at least about 80%, 90% transmission of visible light more preferably from about, and do not produce any image distortion of significantly not expecting.
In an embodiment preferred, lens material has two-phase at least: these phases that comprise at least one oxygen-permeable mutually and at least one ion permeability are mutually.Although two distinct phases are arranged, it is believed that a transition phase or intermediate phase, material composition and performance are the mixing of oxygen-permeable and ion permeability material in transition phase.Therefore, can exist a tangible oxygen-permeable mutually or a plurality of tangible oxygen-permeable phase, tangible ion permeability mutually or a plurality of tangible ion permeability phase, and oxygen-permeable and ion permeability amphiphilic phase mixture mutually.In an embodiment preferred, the second-order transition temperature of oxygen-permeable phase (Tg) is less than-115 ℃ approximately.
Exist isolating oxygen-permeable and ion permeability mutually, rather than oxygen-permeable and ion permeability mixture mutually completely, it is believed that promoting that in the diffusion of oxygen and ionic be favourable.Oxygen will mainly be by the oxygen-permeable polymer diffusion, and the ion permeability polymkeric substance has higher inhibition to the diffusion of oxygen.Similarly, ion will mainly pass through the ion permeability polymer diffusion, but the oxygen-permeable polymkeric substance produces higher inhibition to its diffusion.Therefore, the oxygen-permeable/ion permeability of a homogeneous will produce the inhibition of not expecting to the two the diffusion of oxygen and ion mutually, and two isolating oxygen-permeable will provide the low passage that hinders to seeing through of oxygen and ion or water mutually with ion permeability.Therefore, the lens that ideal can be worn the longer time have the one or a series of passages that oxygen is seen through from outside surface to internal surface, and a similar successive or a series of passage that oxygen is seen through, and a similar successive or a series of passage that water or ion are seen through.In a particularly preferred embodiment, lens have two external phases, and one is the oxygen-permeable phase, and another is the ion permeability phase, and they see through water or ion and oxygen between the front curve of lens and end curved surface.Whole water content
It is difficult measuring water content, is difficult because remove adherent surperficial drop under the situation that does not influence the overall lens water content.In addition, water can promptly evaporate from the surface of lens, has reduced water content thus from balanced contents.Therefore, make the explanation to the measuring technology that is used to measure water content necessitate about the explanation of the whole water content of lens.
The preferred whole water content of hydrated lens will be the function of lens material performance.Material property depends on prepolymerized big monomer and monomer and polymeric condition.Therefore, the preferred water content that comprises the lens of fluorine-containing oxygen-permeable material is different from the water content of the lens that comprise the oxygen-permeable material that contains siloxanes.Therefore, although for understanding the general scope that the present invention has provided whole water content better, the present invention is not subjected to the moisture quantitative limitation of specific integral body usually.
A kind of method of measuring the water content of the lens that form according to the present invention is called " overall technology " here, and this method is as described below.At first make lens thoroughly hydration in normal saline solution, make the water in the lens reach balance with on every side water.Then two nonlinting blotting between the cloth with lens erasing lightly, to remove the moisture on surface.Lens promptly are placed on the aluminium weighing pan, and measure initial weight in wet base W 1Then aluminium dish and lens were positioned over together in 36 ℃ the baking oven at least 24 hours.To coil after the thermal treatment with lens and take out, be placed in the moisture eliminator, make it to be cooled to room temperature (about 22 ℃).And then dish and lens weighed mensuration dry weight W dMake lens in normal saline solution, reach balance once again then, and measure the heavy W of secondary temperature by it 2With weight in wet base W 1And W 2Average, obtain average weight in wet base W wDetermine whole water content by following equation:
Percent moisture=(W w-W d)/W w* 100
Preferably the whole water content of being measured by " overall technology " of lens is less than about 30 weight %.More preferably, based on total lens weight, the water content of lens is about 5～30 weight %.Particularly preferred lens water content is about 10～20 weight %, especially about 10-15 weight %.Relatively low water content obviously is favourable, because it allows higher oxygen transmission rate.Ion and water permeability
Unanticipated be that now definite, ion is closely related through perviousness and its motion on eye of lens.As previously mentioned, need lens to move on eye to guarantee good tear exchange, finally guarantee good corneal health, this is known.Although the present invention is not subjected to the restriction of any theory of proposing here, for understanding mode of the invention process better, it still is useful setting forth some theories.
In theory, for containing the lens that can wear for a long time of oxygen-permeable polymkeric substance as disclosed herein, water-permeable is very important feature.The oxygen-permeable material that contains siloxanes tends to strong adhesion on eye, has therefore limited the motion on eye.The ability that water sees through lens it is believed that and will the polymer lens that contain siloxanes be moved that wherein motion is what to be produced by the water applied force that is squeezed out lens on eye.In case it is believed that the water content that the water-permeable of lens is removed the back complementary lens for pressure also is important.And, it is believed that the ion permeability of lens and water-permeable are in direct ratio.Therefore, ion permeability is the predictor that lens move on eye.
Yet, no matter whether the water-permeable theory is accurately for the understanding of the real motion situation of lens on eye, now be surprised to find that, from the internal surface of lens to outside surface, perhaps conversely, ion is when the perviousness of lens is on a certain threshold value, and lens will move on eye, when being lower than this threshold value, lens will adhere on the eye.Therefore, the innovative contact lens that can wear for a long time of the present invention provides the balance between the higher relatively oxygen-permeable (with relevant high binding ability) of oxygen-permeable material and the lower binding ability of ion permeability material (high eye is gone up motor capacity).It is believed that this sees through passage so that water and ion are realized through lens movement by many successive ions are provided.
Should be pointed out that ion can move by these ionic channels through lens in many ways.For example, ion can be owing to a surface and another surperficial concentration difference and is spread through lens.Ion can also be by the mechanical effect of nictation, and thereupon coming down to of producing water is pushed the squeeze on lens of coming out and is compelled to pass these ionic channels from lens.In addition, Biao Mian charge property also can provide a kind of electric power of ordering about ion through the lens infiltration.A kind of meeting in these motivating forces at a time is greater than another kind, and its relative power can be opposite constantly at another.Proposing these is the motivating forces that will illustrate that the present invention is not limited to this method or makes the ion scioptics.
No matter be, all not conventionally test in industrial test through the water-permeable of ophthalmic lens or the test of ion permeability.Therefore, make the explanation to the measuring technology that is used to measure perviousness necessitate about the explanation of the scope of preferred ion or water permeability.
The water-permeable of lens can be determined from a surface to another surperficial water transmission rates through lens by water.The water-permeable of lens can be measured like this, be about to lens and be placed on two and be equipped with between the water receiver of the aqueous solution that initial concentration is known but different radio-labeling (for example tritium-labeled), measure concentration then as the radio-labeling water in " reception " water receiver (net discharge of canal of radio-labeling water is positive water receiver) of the function of time.
The relative ion permeability of lens can be determined by the ion transmission rates, the ion transmission rates is measured like this, be about to lens and be placed on two and be equipped with between the holder that initial ionic concn is known but different solution, measure then as the specific conductivity in " reception " holder (the ionic net discharge of canal is positive holder) of the function of time.The concentration of ion such as sodium ion can accurately be measured with pH meter and ion selective electrode.It is believed that ion migrates to outside surface through lens by internal surface, or vice versaad, mainly be by the aquaporin diffusion of ion in lens.Ion it is believed that with water in direct ratio through the perviousness of lens through the perviousness of lens.The measuring technology of ionic current (ionoflux)
Following technology is called " ionic current technology " here, is the preferred method of measuring the ion permeability of lens.This technology can be used for measuring competent eye and goes up the possibility of motion.
" ionic current technology " comprises a kind of conductivity meter (LF2000/C of use, accession number 300105, Wissenschaftlich-Technische Werkstatten GmbH (WTW), Germany), a kind of be furnished with temperature sensor (LR01/T, accession number 302520, WTW) electrode, a supply chamber that contains salts solution, a reception chamber that contains the 60ml deionized water of having an appointment, stirring rod and a thermostatic bath.
Supply chamber is designed so that especially contact lens is sealed in wherein so that supply with solution not around lens by (but being only scioptics of ion).Supply chamber comprises the threaded Glass tubing in an end, and this end is immersed in and receives in the solution.Glass tubing comprises that one is positioned at the hole of the about 9mm of diameter of central authorities.On the lens clamping element that covered that screw thread cooperates with Glass tubing is arranged, this element has the hole of the about 8mm of diameter that is positioned at central authorities.The lens clamping element comprises that internal surface (concave surface) edge with lens matches to merge the bossing that makes it to seal and match with outside surface (convex surface) edge of lens and merges the concave portions that makes it to seal.
The lens that to test are placed in the lens clamping element, between bossing and concave portions.Bossing and concave portions comprise mobilizable wear ring, and these wear rings are between lens and each bossing or concave portions.After lens being positioned in the lens clamping element, the lens clamping element is positioned in the threaded lid.This lid is screwed on the Glass tubing, to determine supply chamber.Be full of the NaCl solution of 16ml 0.1M in the supply chamber.Be full of the 60ml deionized water in the reception chamber.The lead of conductivity meter is immersed in the deionized water of reception chamber, and stirring rod is put in the reception chamber.Reception chamber is placed thermostatic bath, and temperature is maintained at about 35 ℃.At last, supply chamber is immersed in the reception chamber.
Be immersed in behind the reception chamber 10 minutes from supply chamber, measured a specific conductivity, carried out altogether about 3 hours every 20 minutes.The ionic current diffusion coefficient D is determined by following with Fick (Fick) law: D=-n '/(A * dc/dx) wherein: the speed of n '=ion migration [mol/min]
Lens area [the mm that A=exposes 2]
D=ionic current spread coefficient [mm 2/ min]
Dc=concentration difference [mol/L]
The thickness of dx=lens [mm]
For reaching the competent motion on eye, preferred ion stream spread coefficient is greater than about 6.4 * 10 -6Mm 2/ min.More preferably, the ionic current spread coefficient is greater than about 2.6 * 10 -6Mm 2/ min, and most preferably, the ionic current spread coefficient is greater than about 1.5 * 10 -6Mm 2/ min.It must be emphasized that the ionic current spread coefficient is relevant through the perviousness of lens with ion, so it is the predictor of moving on eye.
6. embodiment
In following embodiment, the present invention will be by being further described with reference to specific embodiment, and they should not be understood that it is the scope of restriction claims.All temperature are degree centigrade.The preparation embodiment A-1 of A macromole evocating agent
In the 250ml round bottom two neck flasks of being furnished with the Soxhlet extractor, with 29.5g (6.34mmol) α, ω-two (3-hydroxypropyl) polydimethylsiloxane is (by Wacker Chemie, Munich, the IM15 that Germany obtains, purify through thin-film evaporator, 0.43mEq OH/g, Mn=4651) be dissolved in the 90ml hexane, and with its distillation 17 hours under refluxing in nitrogen atmosphere, Soxhlet extractor wherein has condenser, and on second ground joint barrier film is arranged, and is filled with molecular sieve (4 dust) in the Soxhlet extractor.This solution still contains the water of 21ppm afterwards.Subsequently with this solution concentration to the 60ml hexane, be cooled to 0 ℃ and add 3.60g (45.5mmol) pyridine.In 15 minutes, add 12.4g (43.9mmol) trifluoromethanesulfanhydride anhydride (Fluka Chemie AG, Buchs, Switzerland) then, and with this mixture 0 ℃ of restir 30 minutes.After adding 20ml chloroform (water content is less than 10ppm), under vacuum, suspensoid is filtered, under high vacuum (0.6～2 millibar), evaporate then with G4 glass filter funnel.Product is the 18g orange.Then this oily matter is dissolved in the 40ml exsiccant hexane (water content is less than 10ppm), adds gac, then with this mixture stir about 2 minutes and filtration once more.Behind this solution evaporation, product is the colourless oily matter of 15.8g clarification. 1H-NMR (CDCl 3, 250MHz); 0ppm (CH 3-Si), 0.5ppm (CH 2-CH 2-Si-), 1.8ppm (CH 2-CH 2-CH 2-), 4.4ppm (CF 3SO 3CH 2-CH 2-) functionality:＞95% (based on 1The data of H-NMR), promptly＞0.40mEq triflate/g.Embodiment A-2
In the 250ml round bottom two neck flasks of being furnished with the Soxhlet extractor, with 25.6g (5.49mmol) α, ω-two (3-hydroxypropyl) polydimethylsiloxane is (by Wacker Chemie, Munich, the IM15 that Germany obtains, purify through thin-film evaporator, 0.43mEq OH/g, Mn=4651) be dissolved in the 90ml hexane, and with its distillation 17 hours under refluxing in nitrogen atmosphere, Soxhlet extractor wherein has condenser, and on second ground joint barrier film is arranged, and is filled with molecular sieve (4 dust) in the Soxhlet extractor.This solution still contains the water of 16ppm afterwards.Subsequently with this solution concentration to the 50ml hexane, be cooled to 0 ℃ and add 3.26g (41.2mmol) pyridine.In 15 minutes, add 10.25g (36.3mmol) trifluoromethanesulfanhydride anhydride (Fluka Chemie AG, Buchs, Switzerland) then, and with this mixture 0 ℃ of restir 30 minutes.After adding 20ml chloroform (water content is less than 10ppm), under vacuum, suspensoid is filtered, under high vacuum (0.6～2 millibar), evaporate then with the G4 glass filter.Product is the 15.5g orange.Then this oily matter is dissolved in the 40ml exsiccant hexane (water content is less than 6ppm), adds gac, then with this mixture stir about 2 minutes and filtration once more.Behind this solution evaporation, product is the colourless oily matter of 15.4g clarification.Functionality:＞95% (based on 1The data of H-NMR), promptly＞40mEq triflate/g.Embodiment A-3
In the 250ml round bottom two neck flasks of being furnished with the Soxhlet extractor, with 30.9g (10.5mmol) α, ω-two (3-hydroxypropyl) polydimethylsiloxane is (by Wacker Chemie, Munich, the IM11 that Germany obtains, purify through thin-film evaporator, 1.33mEq OH/g, Mn=1503) be dissolved in the 70ml hexane, and with its distillation 17 hours under refluxing in nitrogen atmosphere, be 36ppm until water content, Soxhlet extractor wherein has condenser, and a barrier film is arranged on second ground joint, be filled with molecular sieve (4 dust) in the Soxhlet extractor.Add 20ml exsiccant 1 then, 2-ethylene dichloride (3.6ppm) is cooled to 0 ℃ and add 7.7g (96.9mmol) pyridine with this mixture.In 15 minutes, add 23.4g (82.8mmol) trifluoromethanesulfanhydride anhydride (Fluka Chemic AG, Buchs, Switzerland) and 40ml exsiccant 1 then, the 2-ethylene dichloride, and with this mixture 0 ℃ of restir 30 minutes.Suspended substance is filtered under vacuum with cotton strainer, under high vacuum (0.6～2 millibar), evaporate then.Product is a 35.7g oily matter.Then this oily matter is dissolved in the exsiccant hexane (water content is less than 10ppm), adds gac, then with this mixture stir about 2 minutes and filtration once more.Behind this solution evaporation, product is the colourless oily matter of 21.2g clarification. 1H-NMR (CDCl 3, 250MHz); 0ppm (CH 3-Si), 0.5ppm (CH 2-CH 2-Si-), 1.8ppm (CH 2-CH 2-CH 2-), 4.4ppm (CF 3SO 3CH 2-CH 2-) functionality:＞95% (based on 1The data of H-NMR), promptly＞1.06mEq triflate/g.Embodiment A-4
Have in the membranous 250ml three-necked round bottom flask at an exsiccant, to the highly purified dry chloroform of 100ml (Fluka Chemie AG, Buchs, Switzerland) add the strong exsiccant α of 28.7g in, ω-hydroxyethyl functionalized, molecular-weight average is PFPE (Fomblin, ZDOL TX, the Ausimont S.p.A. of 1146g/mol, Bollate, Italy).This solution is cooled to-60 ℃.
Add 4.15g anhydrous pyridine (Merck7463,99.5%, Merck AG, Darmstadt, Germany) then, in 15 minutes, add 15.55g trifluoromethanesulfanhydride anhydride (Fluka91737, Fluka Chemie AG, Buchs, Switzerland) subsequently lentamente.The suspensoid of gained was stirred 25 minutes down at-60 ℃.Then with mixture heating up to room temperature, and filter with G4 glass filter funnel immediately, and separating obtained salt.By rotatory evaporator and be evacuated to subsequently 0.01 millibar remove all volatile constituents after, obtain yellow, be the buttery clarified liq slightly.Be further purification, this liquid is dissolved in the 80ml chloroform, and add the pugil gac.Stir after 5 minutes, through Hyflo (Fluka Chemie AG, Buchs, Switzerland) mixture is filtered, and solvent is thoroughly removed under vacuum.Obtain the colourless viscous liquid of 15.6g clarification.Embodiment A-5
Will (Aldrich numbers 19,079-9 corresponding to the 5.6g polybutadiene diol of 4.4mEq OH; 0.79mEq-OH/g) be dissolved in the 130ml exsiccant hexane.In the Soxhlet extractor that is filled with 4 dust molecular sieves, with this solution under refluxing dry 2 hours.Carry out titration according to Karl Fischer: 15ppm water.The distillation of 80ml hexane is entered in the Soxhlet extractor, and this polymers soln is cooled off in ice bath.Add down 2.6g (=33mmol) anhydrous pyridine at 0～5 ℃.In 30 minutes, be added dropwise to then the 9.0g trifluoromethanesulfanhydride anhydride (=33mmol), it has caused the pasty state precipitation.After adding 20ml toluene and 20ml chloroform, this solution is carried out brief stirring, and filter with a G4 strainer.Evaporate limpid solution and drying under high vacuum.Obtain clarification product colourless, high viscosity.Pass through the content of titration determination triflate then: 0.66mEq/g is equivalent to 92.3% of theoretical value (0.71mEq).Embodiment A-6
Similar with embodiment A-5, reaction be that (PolySciences number 06508 for the polybutadiene diol of a kind of molecular-weight average about 2100; 0.97mEq-OH/g).Embodiment A-7
Similar with embodiment A-5, with 5.6g polybutadiene diol (Aldrich 19079-9) and 2.6g pyridine and the reaction of 9.0g trifluoromethanesulfonic acid.Replace toluene/chloroform as solvent with pure chloroform.The big monomeric productive rate of polyhutadiene-two-triflate is 97%.Embodiment A-8
Will (Aldrich numbers 19,079-9 corresponding to the 10.0g polybutadiene diol of 7.90mEq; 0.79mEq-OH/g) be dissolved in the 130ml exsiccant hexane.In being filled with the Soxhlet extractor of molecular sieve 4, with this solution under refluxing dry 2 hours.Carry out titration according to Karl Fischer: 15ppm water.
Subsequently this solution is added dropwise to lentamente 1.76g isophorone diisocyanate (M=222; Be equivalent to 7.90mmol) and the mixture of 10mg dibutyl tin dilaurate in.After reaction takes place, with this drips of solution add the 14.80g polydimethylsiloxanediols diols that is equivalent to 15.8mEq-OH (Shinetsu KF-6001,1.07mEq-OH/g) in, and at room temperature stir and spend the night.Triblock copolymer with gained joins in the 5.2g pyridine (being equivalent to 65mmol) then.Added 18.4g trifluoromethanesulfanhydride anhydride (M=282.13) (being equivalent to 65mmol) under 0～5 ℃ in 30 minutes, it has caused the pasty state precipitation.After adding 20ml toluene and 20ml chloroform, this solution is carried out brief stirring, and filter with a G4 strainer.In a rotatory evaporator, evaporate limpid solution, and under high vacuum, remove residual solvent subsequently.Obtain clarification product colourless, high viscosity.Pass through the content of titration determination triflate then: 0.349mEq trifluoromethanesulfonic acid ester group/g is equivalent to 97.5% of theoretical value.Embodiment A-91.) the hydrophobicity block of being made up of each seed block is synthetic
22.2g (0.1mol) new distillatory isophorone diisocyanate and 50mg dibutyl tin dilaurate under argon gas are joined in the three-necked flask.Adding 51.5g (50mmol) molecular-weight average in dropping funnel is the PFPE Fomblin of 1030g/mol, and ZDOL (by Ausimont S.p.A., Milan obtains) is 1.96mEq/g according to its hydroxy radical content of end group analysis.This dropping funnel is contained on the three-necked flask, under agitation this device is evacuated to about 20 millibars then, charge into argon gas subsequently and make system not be subjected to stress.Repeat twice of this process.Dripped PFPE then 2 hours.By in water-bath, cooling off, the temperature of flask is remained on below 30 ℃.After stirring was spent the night under the room temperature, reaction was finished.The content of isocyanic ester titration demonstration-NCO is 1.40mEq/g (theoretical value: 1.35mEq/g).
In flask, add 202g α, ω-hydroxypropyl terminated, molecular-weight average is polydimethylsiloxane KF-6001 2000g/mol (is 1.00mEq/g according to the titration hydroxy radical content), that obtained by Shinetsu.Flask is evacuated to about 0.1 millibar, charges into argon gas again and make system not be subjected to stress.Repeat twice of this process.The siloxanes of the degassing is dissolved in 202ml newly distills and be kept in toluene argon gas under, and adding 100mg dibutyl tin dilaurate.After the complete homogenizing of this solution, under hydrogen, add whole PFPE of reacting that measure with IPDI.After stirring was spent the night under the room temperature, reaction was finished.Under high vacuum, solvent is removed under the room temperature.Microtitration signify hydroxy content is 0.37mEq/g (theoretical value: 0.37mEq/g).2.) two triflate macromole evocating agents is synthetic
Have in the membranous dry 250ml three-necked round bottom flask one, the polydimethylsiloxane PFPE triblock copolymer that 33.2g is hydroxy-end capped outgases, and carries out drying under 80 ℃ of temperature, 0.1 millibar of pressure.Add 80ml exsiccant hexane after being cooled to room temperature, and this solution is cooled to 0 ℃.Add 2.45g anhydrous pyridine (Merck7463 then; 99.5%), in 15 minutes, adds 8.68g trifluoromethanesulfanhydride anhydride (Fluka91737) subsequently lentamente.The viscosity suspensoid of gained stirred 25 minutes down at 0 ℃.Then with this mixture heating up to room temperature, dilute with other 80ml hexane, and filter to remove the salt of gained with the G4 glass filter immediately.After in resulting pressure is 0.01 millibar rotatory evaporator, removing all volatile constituents, obtain xanchromatic, be the buttery clarified liq slightly.Embodiment A-10
In the 250ml round bottom two neck flasks of being furnished with the Soxhlet extractor, with 33.85g (6.69mmol) α, ω-two (3-hydroxypropyl acyl ethyl (hydroxypropyloylethyl)) polydimethylsiloxane is (by the KF6003 of Japanese Shin-Etsu acquisition, purify through thin-film evaporator) be dissolved in the hexane, and with its distillation 17 hours under refluxing in nitrogen atmosphere, Soxhlet extractor wherein has condenser, and a barrier film is arranged on second ground joint, be filled with molecular sieve (4 dust) in the Soxhlet extractor.Subsequently with this solution concentration to the 85ml hexane, be cooled to 0 ℃ and add 3.88g (49.05mmol) anhydrous pyridine.In 15 minutes, add 12.8g (44.23mmol) trifluoromethanesulfanhydride anhydride then, and with this mixture 0 ℃ of restir 30 minutes.After adding the 20ml chloroform and adding the 8ml hexane subsequently, under vacuum, suspensoid is filtered, under high vacuum (0.6～2 millibar), evaporate then with G4 glass filter funnel.The colorless oil of gained is dissolved in the 13ml hexane once more, adds gac, and once more mixture is filtered.After the evaporation, product is the colourless oily matter of 20.6g clarification.Functionality:＞95% (based on 1The data of H-NMR).The preparation Embodiment B-1 of B amphiphilic block copolymer
Macromole evocating agent with preparation in 2.22g (26.1mmol) 2-methyl-2-oxazoline and 6.94g (1.4mmol) embodiment A-1 under the room temperature joins 15ml 1, in the 2-ethylene dichloride (water content 5ppm).Stirred solution rose to 40 ℃ with temperature after 1.5 hours under the room temperature.After 48 hours solution is cooled to room temperature, and adds the KOH/EtOH solution of 5.5ml 0.5N.With this solution stirring 1 hour, under high vacuum (0.6～2 millibar), evaporate subsequently then. 1H-NMR; 0ppm (CH 3-Si), 2.0～2.1ppm (CH 3CON＜), 3.3～3.5ppm (＞N-CH 2-CH 2-N＜) functionality: OH titration: 0.40mEq/g
The titration of residue positively charged ion end group: 0.02mEq/g is that the GPC that elutriant carries out measures with THF:, bring out existing one peak that has an acromion in lower molecular weight one, it is about 6500 that maximum peak appears at, and makes standard based on polystyrene.Embodiment B-2
In a 25ml pyriform bottle, the macromole evocating agent (2.12mmol) of 3.1g embodiment A-4 preparation is dissolved in 7.1ml anhydrous chloroform (Fluka25690 Chemie AG, Buchs, Switzerland) in, and add 1.8g (21.2mmol) exsiccant 2-methyl-2-oxazoline.Mixture stirring under 40 ℃ is spent the night.Subsequently, by 1H-NMR detects the monomer complete reaction.Embodiment B-3
The exsiccant macromole evocating agent (being equivalent to the 0.33mEq triflate) of 0.5g embodiment A-5 preparation is dissolved in exsiccant 1, in the 2-ethylene dichloride.Add 1.0g 2-methyl-2-oxazoline (being equivalent to 12mmol) subsequently.This solution at room temperature stirred 30 minutes, stirred 48 hours down at 60 ℃ then.Under high vacuum,, obtain the solid triblock copolymer of white except that after desolvating.Embodiment B-4
Described in Embodiment B-3, polyhutadiene/polydimethylsiloxane macromole evocating agent that 2.5g (0.873mEq trifluoromethanesulfonic acid ester group) is obtained in embodiment A-8 is dissolved in 100ml exsiccant 1, in the 2-ethylene dichloride, after adding 2.45g (28.8mmol) 2-methyl-2-oxazoline, this solution was stirred 48 hours down at 70 ℃.With solution evaporation to the total amount of gained is 30ml, precipitates in methyl alcohol subsequently.From the viscous precipitate thing, remove under the high vacuum desolvate and unreacted monomer after, obtain the clarifying high viscosity product of 4.8g (theoretical value 97%).Preparation Embodiment B-5 with amphiphilic block copolymer of terminal hydroxy group
Similar with Embodiment B-3, replace 1 with the exsiccant acetonitrile, the 2-ethylene dichloride, the exsiccant macromole evocating agent that 0.5g embodiment A-5 is prepared is dissolved in wherein, and reacts with 2-methyl-2-oxazoline.Add then equimolar amount, the 0.5N solution of KOH in ethanol, and it was stirred 30 minutes.Product is dry under high vacuum, is dissolved among the THF, adds gac, and product is filtered and drying.Obtain white solid terminal hydroxy group multipolymer.Embodiment B-6
As described in the Embodiment B-5, the multipolymer that still contains the trifluoromethanesulfonic acid ester terminal that 1g is obtained in Embodiment B-3 is dissolved in the ethylene dichloride, and handles with KOH/EtOH.After method is as described handled and purified, obtain the colourless terminal hydroxy group multipolymer (0.17mEq HO-/g) of 0.96g clarification.Embodiment B-7
In a 500ml pyriform bottle, it is anhydrous 1 that the macromole evocating agent (2.85mmol) of 15.4g embodiment A-9 preparation is dissolved in 25ml, in the 2-ethylene dichloride, and adds 5.82g (68.4mmol) exsiccant 2-methyl-2-oxazoline.The stirring under 40 ℃ of this mixture is spent the night.Subsequently, by 1H-NMR detects monomeric entire reaction.The ethanolic soln (5.7mmol KOH) that in this solution, adds the potassium hydroxide of 11.4ml 0.5M then, and it was at room temperature stirred 1 hour.Then this solution is evaporated, and (0.01 millibar) removes all volatile constituents under vacuum.Embodiment B-8
The macromole evocating agent of 18.4g embodiment A-10 is dissolved in 60ml exsiccant 1, in the 2-ethylene dichloride.Add 6.1g 2-methyl-2-oxazoline subsequently.This solution was at room temperature stirred 30 minutes, stirred 48 hours down at 40 ℃ then.Add 11.6g KOH/MeOH (0.507N) subsequently.After following 1 hour of the room temperature, under 120 milli torrs, solvent was evaporated 17 hours.Embodiment B-9
The macromole evocating agent that 6.9g is similar to embodiment A-10 is dissolved in 15ml exsiccant 1, in the 2-ethylene dichloride.Add 2.2g 2-methyl-2-oxazoline subsequently.This solution was at room temperature stirred 30 minutes, stirred 2 hours down at 70 ℃ then.Add 4ml KOH/MeOH (0.507N) subsequently.After following 1 hour of the room temperature, under 120 milli torrs, solvent evaporated and spend the night.The preparation Embodiment C-1 of the amphiphilic block copolymer that C is functionalized
In a round-bottomed flask; the amphiphilic block copolymer that obtains in 6.62g (2.64mEq) Embodiment B-1 is dissolved under room temperature in the 20ml exsiccant ethyl acetate (water content is less than 10ppm), and adds 420mg (2.7mmol) methacrylic acid 2-isocyanide acyl group ethyl ester (IEM) and about 40mg dibutyl tin dilaurate.With this solution stirring 48 hours, under 0 ℃, (0.6～2 millibar) was with its evaporation 5 hours under high vacuum then under unglazed.Obtain the big monomer of 6.89g colorless solid.Functionality: OH titration: 0.11mEq/g (27.5%-OH group unreacted) is that the GPC that elutriant carries out measures with THF: 2 peaks, maximum peak appear at 400 (small peaks) and 6500, are standard based on polystyrene.Embodiment C-2
In a round-bottomed flask; the amphiphilic block copolymer that obtains in 18.0g (6.48mEq-OH) Embodiment B-1 is dissolved under room temperature in the 40ml exsiccant ethyl acetate (water content is less than 20ppm), and adds 1.04mg (6.7mmol) methacrylic acid 2-isocyanide acyl group ethyl ester (IEM) and about 40mg dibutyl tin dilaurate.Add two parts of each 40mg dibutyl tin dilaurates after 45 hours and 69 hours.After 24 hours, in this solution, add 2ml methyl alcohol, with the micro-filter of 0.45 μ m micropore this solution is filtered, under 0 ℃, (0.6～2 millibar) evaporates it under high vacuum then.Obtain the big monomer of 18.1g solid.Functionality: OH titration: 0.05mEq/g
Two keys: 0.37mEq/g Embodiment C-3
The ethanolic soln (4.24mmol KOH) of the potassium hydroxide of 8.5ml 0.5M is joined the reaction mixture that obtains in the Embodiment B-2, and this mixture was at room temperature stirred 1 hour.Then solvent is evaporated, and (0.01 millibar) removes all volatile constituents under vacuum.The concentration that titrimetry demonstrates hydroxyl is 1.05mEq/g.
Then the reaction mixture that obtains is dissolved in the 14ml anhydrous methylene chloride, and adds 0.6g (3.9mmol) methacrylic acid 2-isocyanide acyl group ethyl ester and 1 dibutyl tin dilaurate.Room temperature is unglazed spends the night the mixture stirring down.Infrared spectra shows isocyanate-free base in the solution.Then with the mixture alcohol dilution, and on being 5 bed of aluminium oxide, activity filters lentamente.Filtrate is evaporated, and under 0.01 millibar, remove all volatile constituents.Obtain stone solid matter.Titrimetry shows that the amount of carbon-carbon double bond is 0.95mEq/g.The content of hydroxyl and isocyanate group is all below limit of detection 0.01mEq/g.Embodiment C-4
In the three-necked round bottom flask that a brown glass is made; the terminal hydroxy group segmented copolymer that obtains in 15.53g (the 2.64mEq HO-group) Embodiment B-6 is dissolved under unglazed in the 50ml exsiccant ethyl acetate; stirred solution the time, add 420mg (2.7mmol) methacrylic acid 2-isocyanide acyl group ethyl ester (IEM) and 40mg dibutyl tin dilaurate under the room temperature as catalyzer.React after 48 hours, under 0 ℃, 0.6 millibar, from mixture, removed in shared 10 hours and to desolvate and excessive IEM.Obtain the product of the clarifying high viscosity of 15.85g, be equivalent to 99% of theoretical value.It is 0.16mEq/g that unsaturated end group is carried out the value that titration obtains.Embodiment C-5
As described in the Embodiment B-4, the amphiphilic block copolymer that makes is made up of an intermediary polyhutadiene/polysiloxane block and two poly-2-methyl-2-oxazoline end blocks.Not that it is precipitated in methyl alcohol, desolvate but under high vacuum, from product, remove up hill and dale.The product of 10g gained is dissolved in the 50ml exsiccant Nitromethane 99Min., makes active San fluorine Jia Huang Suan oxazoline end group and vinylformic acid and 2 subsequently, the reaction of 6-lutidine.For this point, the reaction of Nitromethane 99Min. solution is according to document (M.Miyamoto etc., macromole 22,1604-1607 page or leaf (1989)) described, promptly under 70 ℃, with 2 of the stoichiometric vinylformic acid of twice and 6 times of amounts, the 6-lutidine reacted 24 hours.After spent ion exchange resin is as described handled, obtain the end acryl product of the clarifying high viscosity of 9.2g.Unsaturated end group is carried out titration, and the value that obtains is 0.14mEq/g, is equivalent to 82.3% of theoretical value.Embodiment C-6
The reaction mixture that Embodiment B-7 is obtained is dissolved in the 30ml anhydrous methylene chloride, and adds 0.88g (5.7mmol) methacrylic acid isocyanide acyl group ethyl ester and 1 dibutyl tin dilaurate.Room temperature is unglazed spends the night the mixture stirring down.Infrared spectra shows isocyanate-free base in the solution.Then with the mixture alcohol dilution, and on being 5 bed of aluminium oxide, activity filters lentamente.Filtrate is evaporated, and under 0.01 millibar, remove all volatile constituents.Obtain stone solid matter.Titrimetry shows that the amount of carbon-carbon double bond is 0.25mEq/g.The content of hydroxyl and isocyanate group is all below limit of detection 0.01mEq/g.
Thus, by sequentially carrying out the reaction of embodiment A-9, B-7 and C-6, can obtain a kind of amphiphilic block copolymer (wherein the hydrophobicity block is made up of each seed block, and contains polymerisable end group in the wetting ability block).Embodiment C-7
Triblock copolymer in the Embodiment B-8 is dissolved in the 72g chloroform once more, and adds 0.92g (6.3mmol) methacrylic acid 2-isocyanide acyl group ethyl ester (IEM).Add 35ml ethanol two days later,, filter with the strainer of 0.45 μ m, and under 150 milli torrs, carry out stripping solution stirring 1 hour.Embodiment C-8
Triblock copolymer in the Embodiment B-9 is dissolved in the 30ml methylene dichloride once more, and adds 0.73g (7.2mmol) exsiccant triethylamine and 0.567g (6.3mmol) acrylate chloride.Place under the room temperature after 24 hours, with the strainer of 0.45 μ m suspensoid is filtered, and carry out stripping under the torrs in the least 150.The mensuration embodiment D-1 of the preparation of D film and form
With functionalized amphiphilic block copolymer and the 0.26g1 that obtains in the 4.14g Embodiment C-1, two (3-methacryloxypropyl) tetramethyl--sily oxide (linking agent) of 3-are dissolved in the 4.4g 1-propyl alcohol, and it is filtered with the micro-filter of 0.45 μ m micropore under pressure.In the filtering solution of 6.9g, add 16.9mg light trigger (Darocur1173 , CIBA SpecialtyChemicals Inc., Basel, Switzerland).Then with this solution in liquid nitrogen freezing three times with the degassing, flask (1.2 millibars) under high vacuum is vacuumized, be heated to room temperature then.By from spread over the batching on the glass surface thinly, film being carried out curtain coating except that desolvating.With after the OsO4 dyeing, optical clear film (less than 100nm) in sub-micrometer range demonstrates lamellated microcosmic phase structure under transmission electron microscope.
The film of gained is under reduced pressure carried out the drying and the degassing, then it is used ultraviolet ray (15mW/cm in the silicon-dioxide flask 2) shine.Extract transparent film with Virahol crosslinked back.The amount that can extract part is about 30%.Transmission electron microscope shows that it has lamellar morphologies, because this point, two kinds of polymer blocks can be distinguished at an easy rate mutually.The thickness of PDMS layer is about 4nm for the thickness of about 10nm ， Ju oxazoline layer.The size of matrix laminate microcell is less than 1 μ m.The three-dimensional arrangement of these microcells generates co-continuous form on the whole in the matrix.The preparation embodiment E-1 of E contact lens
With functionalized amphiphilic block copolymer and the 0.26g1 that obtains in the 4.14g Embodiment C-1, two (3-methacryloxypropyl) tetramethyl--sily oxide (linking agent) of 3-are dissolved in the 4.4g 1-propyl alcohol, and it is filtered with the micro-filter of 0.45 μ m micropore under pressure.In the filtering solution of 6.9g, add 16.9mg light trigger (Darocur1173 , CIBA SpecialtyChemicals Inc., Basel, Switzerland).Then with this solution in liquid nitrogen freezing three times with the degassing, flask (1.2 millibars) under high vacuum is vacuumized, be heated to room temperature then.In polyacrylic contact lens mould, in nitrogen atmosphere (remaining oxygen content is less than 3ppm), make this batching accept 15mW/cm 2Uviolizing 5 minutes.The lens that the clarification of gained is colourless place Virahol to carry out swelling, and extract 2 days in Virahol, make it to rebulid balance in the water with being placed on.121 ℃ of following high-temperature sterilizations 30 minutes, carry out disinfection to reaching the equilibrated lens again.The lens of high-temperature sterilization are carried out the mensuration of physical parameter.Ionic diffusion coefficient is 3.93 * 10 -5Mm 2/ min, perhaps, with respect to Alsacon NC (as standard, for test referring to above-mentioned ionic current measuring technology): 1.25 (ion-flow rates)
O 2D k[barrers]:102
Water regain [%w/w]: 14
E modulus [MPa]: 1.2
Tear strength [MPa]: 1.1
Elongation at break [%]: 130 embodiment E-2 are to E-8
According to embodiment E-1, prepared the contact lens that provides in the table 1 (table 1a and table 1b), as described it is carried out high-temperature sterilization and sign: table 1a
Lens PMOXA [％w/w] Linking agent [%w/w] Water regain [%w/w] Ion-flow rate [* 10 -5mm 2/min]
Embodiment E-2 * 13.6 5.2 7 0.19
Embodiment E-3 * 22.5 5.2 15 3.14
Embodiment E-4 19.7 7.2 11 1.73
Embodiment E-5 22.4 5.9 15 2.17
Embodiment E-6 21.0 0 - 4.33
Embodiment E-7 ° 22.3 0 - 5.65
Embodiment E-8 23.8 0 13 1.22
Table 1b
Lens E[MPa] σR[MPa] ??S R[％] O 2D k[barrers]
Embodiment E-2 * 0.9 0.8 250 174
Embodiment E-3 * 1.6 1.0 210 121
Embodiment E-4 1.7 1.0 170 139
Embodiment E-5 2.3 1.3 130 106
Embodiment E-6 1.3 0.4 35 146
Embodiment E-7 ° - 0.4 34 15
Embodiment E-8 2.4 1.3 115 123
*) in batching, use ethyl acetate as solvent °) the Mn=1500 E=E-modulus of PDMS block σR=tear strength S RThe lens that=elongation at break is made by Embodiment C-7 except that table 1a and 1b: batching: the big monomer of 50%w/w, 50%w/w1-propyl alcohol, but 0.5%w/w Darocur1173PMOXA%w/w:25 extracted amount: 9%w/w water content 23%w/wE-modulus: 1.2MPa elongation at break: 69%Dk:48 micron thickness place is the 56barrers ion-flow rate: 3.8 embodiment E-9
With functionalized copolymers, the 66mg 1 that obtains in the 1.17g Embodiment C-2, two (3-methacryloxypropyl) tetramethyl--sily oxide (linking agent) of 3-and 9mg Darocur1173 , CIBA Specialty Chemicals Inc., Basel, Switzerland's (light trigger) is dissolved in the 1.21g l-propyl alcohol.With half of this batching in liquid nitrogen freezing three times, flask (1.2 millibars) under high vacuum is found time, before it fills in the polypropylene contact lens mould, make the solution in the sealing flask (degassing) turn back to room temperature then.Second half unprocessed just filling in the polypropylene contact lens mould of batching.Two portions batching all is subjected to 22.5mW/cm 2Uviolizing 10 minutes.Place Virahol to carry out swelling on the water white transparency lens of gained, and in Virahol, extracted at least 30 hours, make it to rebulid balance in the water with being placed on.Under 121 ℃, carry out high-temperature sterilization processing 30 minutes to reaching the equilibrated lens again.Lens to high-temperature sterilization carry out physical parameter measurement, are listed in the table 2.Table 2
Lens O 2Dk[barrers] Ion-flow rate [* 10 -5mm 2/min] Water regain [%w/w] Can extract part [%w/w]
Embodiment E-9 (the not degassing) 102 2.67 14.4 11.1
Embodiment E-9 (degassing) 105 3.30 14.9 10.3
Embodiment E-10 comonomer N, N-DMAA (DMA)
The N,N-DMAA that in the batching that is similar to embodiment E-5, adds 24%w/w.Be similar to embodiment E-1, this batching is shone and extract.The water regain of gained lens is 42%w/w, and ion transmission is 17.58 * 10 -5Mm 2/ min (5.6) with respect to AlsaconNC, O 2Dk is 33barrers, and the E-modulus is 2.4MPa, and elongation at break is 105%.Embodiment E-11 comonomer TRIS:
Methacrylic acid 3-[three (the trimethylsiloxy)-silyl that in the batching that is similar to embodiment E-5, adds 24%w/w] propyl ester (TRIS).Be similar to embodiment E-1, this batching is shone and extract.The water regain of gained lens is 11.5%w/w, and ion transmission is 0.63 * 10 -5Mm 2/ min (0.2) with respect to Alsacon NC, O 2D kBe 132barrers, the E-modulus is 1.4MPa, and elongation at break is 145%.Embodiment E-12EGDMA is as a kind of selectable linking agent:
In the batching that is similar to embodiment E-5, replace original linking agent with linking agent Ethylene glycol dimethacrylate (EGDMA).Be similar to embodiment E-1 preparation lens.The water regain of gained lens is 9.8%w/w, and ion transmission is 0.44 * 10 -5Mm 2/ min (0.14) with respect to Alsacon NC, O 2D kBe 115barrers, the E-modulus is 2.6MPa, and elongation at break is 90%.Embodiment E-13
The functionalized copolymers that obtains in the 1.56g Embodiment C-3 is dissolved in the 0.56g ethanol, and adds 10mg light trigger Darocur1173 (CIBA Specialty Chemicals Inc., Basel, Switzerland).For removing the oxygen in the atmosphere, the flask that will contain this solution is freezing in liquid nitrogen, is evacuated to 0.01 millibar and be back to room temperature.Repeat twice of this process.The flask that this is vacuumized is introduced in the glove box that is full of nitrogen subsequently, here big monomeric de-gassed solution is metered into to polypropylene contact lens mould with transfer pipet.Mould closed and be 15mW/cm with intensity 2Uviolizing 5 minutes.Mould is taken out from glove box and opens.The contact lens of gained extracted in Virahol 24 hours, made it reach balance in the sodium chloride solution of phosphate buffered, and 121 ℃ of following high-temperature sterilizations 30 minutes.But the extraction unit of the contact lens of gained in methylene dichloride is divided into 3.1%w/w, and water regain is 24.5%w/w, and ion-flow rate is that ion transmission is 6 * 10 -5Mm 2/ min.

Claims (55)

1. amphiphilic block copolymer that contains at least one block A and at least one B block, wherein block A contains a kind of oxygen-permeable polymkeric substance, B block contains a kind of ion permeability polymkeric substance, block A and B link together by the key of a non-hydrolysable, and wherein this multipolymer contains at least one polymerisable unsaturated group.
2. the multipolymer of claim 1, wherein block A contains the polysiloxane of logical formula I:
Figure A9719587600021
Wherein n is 5 to 200 integer; Alk is the alkylidene group of 20 carbon atoms at the most; 80～100% radicals R 1, R 2, R 3And R 4Be alkyl independently of each other, 0～20% radicals R 1, R 2, R 3And R 4Be alkenyl, aryl, fluoro-alkyl or cyano group alkyl independently of each other.
3. the multipolymer of claim 2, wherein n is 5 to 120 integer, and is preferred 10 to 100, particularly 20 to 80.
4. the multipolymer of claim 2, wherein 85～100%, 90～100% radicals R particularly 1, R 2, R 3And R 4Be the low alkyl group of 8 carbon atoms at the most independently of each other, the preferred low alkyl group of 4 carbon atoms at the most, the preferred especially low alkyl group of 2 carbon atoms at the most.
5. the multipolymer of claim 2, wherein 0～15%, 0～10% radicals R particularly 1, R 2, R 3And R 4Be low-grade alkenyl independently of each other, the phenyl that replaces or replaced by low alkyl group or lower alkoxy, fluoro low alkyl group or cyano-lower alkyl group.
6. the multipolymer of claim 1, wherein block A contains the perfluoroalkyl polyethers of logical formula II:
-(E) k-Z-CF 2-(OCF 2) x-(OCF 2CF 2) y-OCF 2-Z-(E) k(II) wherein x+y is number in 10 to 100 scopes; Each Z is divalent group or key of 12 carbon atoms at the most independently of each other; Each E is-(OCH independently of each other 2CH 2) q-, wherein the statistical average value of q is 0 to 2, connection-Z-E-represents sequence-Z-(OCH 2CH 2) q-; And k is 0 or 1.
7. the multipolymer of claim 6, wherein Z is a key, low-grade alkylidene or-the CONH-arylidene, wherein-CO-partly is connected in CF 2On the group.
8. the multipolymer of claim 6, wherein Z is a low-grade alkylidene.
9. the multipolymer of claim 6, wherein index x+y is 10 to 50, preferred 10 to 30 number.
10. the multipolymer of claim 6, wherein the scope of ratio x: y is 0.5 to 1.5, particularly 0.8 to 1.2.
11. the multipolymer of claim 1, wherein block A contains a kind of unsaturated polymer that is selected from logical formula III and (IV) unitary repeating unit that comprises:
Figure A9719587600031
R wherein 5Be hydrogen, alkyl or trialkylsilkl; R 6Alkyl for unsubstituted or alkoxy, alkoxy carbonyl, hydroxyl, carboxyl, halogen or aryl replacement; The alkenyl unsubstituted or alkoxy, alkoxy carbonyl, carboxyl, halogen or aryl replace; Or alkynyl unsubstituted or that alkoxy, alkoxy carbonyl, carboxyl, halogen or aryl replace; And R 7And R 8Be hydrogen or alkyl independently of each other; Perhaps R 6And R 7Combine and be-(CH 2) p-, wherein p is 3 to 5 integer; Perhaps R 6And R 7Combine and be the residue of divalent of general formula (V):
Figure A9719587600032
Wherein r and s are 1 to 3 integer independently of each other, but are not 1 simultaneously; Perhaps R 7And R 8Combine and be-(CH 2) p-, wherein p as above defines; M and o are 10 to 100000 integer independently of each other; With the summation of m and o be 20 to 100010 integer.
12. the multipolymer of claim 11, wherein unsaturated polymer contains and is selected from logical formula III and (IV) unitary repeating unit, wherein R 5, R 7And R 8Be hydrogen, R 6Be low-grade alkenyl or the low-grade alkenyl that replaced by halogen, the preferred low-grade alkenyl of 4 carbon atoms at the most.
13. the multipolymer of claim 11, wherein unsaturated polymer contains the repeating unit of logical formula IV, wherein R 5Be three low alkyl group silyls, R 6Be low alkyl group.
14. the multipolymer of claim 11, wherein unsaturated polymer contains alternately repeating unit, the wherein R of logical formula III and (IV) 5, R 7And R 8Be hydrogen, R 6Be the low alkyl group or the low-grade alkenyl of 4 carbon atoms at the most.
15. the multipolymer of claim 11, wherein unsaturated polymer is selected from syndiotaxy 1,2-polyhutadiene, 1 and polyisoprene.
16. the multipolymer of claim 1, wherein block A contains and comprises at least one structural unit VI a) to VI d) polysulfones:
-R-SO 2-?????????????????Ⅵa)
Figure A9719587600041
-R-SO 2-R-O-?????????????Ⅵc)
-R-O-R-SO 2-R-R-SO 2-VI d) wherein the structural unit VI a) in R be alkylidene group or arylidene, at structural unit VI b), VI c) and VI d) in R be arylidene, particularly phenylene.
17. the multipolymer of claim 1, wherein block A contains two or more following sub-blocks that are selected from: the polysiloxane of the logical formula I of definition in claim 2 to 5, the perfluoroalkyl polyethers of the logical formula II of definition in claim 6 to 10, the unsaturated polymer of the repeating unit that contains logical formula III and (IV) of definition in claim 11 to 15, and the polysulfones of definition in claim 16.
18. the multipolymer of claim 1 and 17, wherein block A contains perfluoroalkyl polyethers or sub-block of polyhutadiene (a) and the sub-block of polysiloxane (b).
19. each multipolymer of claim 1 to 18, wherein B block is derived from the cyclic imide base ether compound of general formula (VII):
Figure A9719587600051
R wherein 9Expression hydrogen atom, 22 carbon atoms and randomly contain the alkyl of ether, ester or urethane groups, hydroxyalkyl or alkenyl, cycloalkyl, aralkyl or aryl at the most; T is 2 or 3.
20. the multipolymer of claim 19, wherein cyclic imide base ether compound is 2-alkyl or 2-Lian Xi oxazolin, or 2-(hydroxyalkyl) oxazoline or their methacrylic acid 2-isocyanide acyl group ethyl ester adducts.
21. the multipolymer of claim 20, wherein cyclic imide base ether compound is a 2-Jia oxazolin, 2-(methylol) oxazoline or 2-(hydroxyethyl) oxazoline.
22. each multipolymer of claim 1 to 18, wherein B block is derived from the vinyl ether of general formula (VIII):
R 10-O-CH=CH 2(VIII) be R wherein 10Be the alkyl or the alkoxyalkyl of 1-10 carbon atom, dioxolane, the cyclic ether of dioxetane or general formula (IX), (X) or (XI): Wherein u is 1 to 3 integer, each R 11Represent hydrogen or 22 carbon atoms and randomly contain the alkyl or the alkenyl of ether, ester or urethane ester group at the most independently, or be cycloalkyl, aralkyl or aryl, R 12Be the alkyl of 4 carbon atoms, alkenyl or alkoxyalkyl at the most.
23. the multipolymer of claim 22, therein ethylene base ether is methylvinylether, ethyl vinyl ether or methoxy ethyl vinyl ether.
24. the multipolymer of claim 22, wherein cyclic ether is a trimethylene oxide.
25. the multipolymer of claim 22, wherein cyclic ether is oxyethane or propylene oxide.
26. the multipolymer of claim 22, wherein cyclic ether is a methyl glycidyl ether, vinyl glycidyl ether, glycidyl allyl ether or ethoxyethyl group glycidyl ether.
27. each multipolymer of claim 1 to 18, the wherein aziridine, β-lactone or the beta-lactam that replace derived from N-of B block.
28. each multipolymer of claim 1 to 27, this multipolymer is the Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock that contains a block A and a B block.
29. each multipolymer of claim 1 to 27, this multipolymer is to contain a block A and two B block that are connected block A end, or contains a B block and two triblock copolymers that are connected the block A of B block end.
30. each multipolymer of claim 1 to 27, this multipolymer is the comb copolymer of general formula (XII) or (XII '):
Figure A9719587600061
Wherein B block is that side chain or the block A of block A are the side chain of B block, and v is 0 to 20 integer.
31. the multipolymer of claim 29 or 30, wherein other hydrophobicity block A ' that forms by the monomer that is same or different from block A and B and/or other wetting ability B block ' the be connected end of block A or B.
32. each multipolymer of claim 1 to 31, wherein at least one polymerisable unsaturated group is present in any one block A, B, A ' or the B ', or is present in the end of holding block.
33. one kind prepares each the method for multipolymer of claim 1 to 32, this method comprises the steps:
A) in multipolymer, be used as and provide at least one can heat or photochemistry activatory positively charged ion or radical initiator group at least one end group of compound of block A or B block or the side group;
B) on the initiator group that is present on described block A or the B block, carry out graft polymerization, form B block or block A respectively by this monomeric polymerization with a kind of monomer;
C) randomly change monomer and carry out other graft polymerization with a kind of and the monomer that constitutes block A and B identical or different hydrophobicity or hydrophilic monomer, with prepare other hydrophobicity block A ' and/or other wetting ability B block ';
And if should provide polymerisable final unsaturated group at the end that increases block, then
D) thus obtained segmented copolymer or its appropriate derivative and the functionalized compounds with polymerizable unsaturated group are reacted.
34. the polymerisate that can obtain by each the further polymerization of polymerizable unsaturated group of multipolymer of claim 1 to 32, randomly this polymerization be other vinyl comonomer and randomly contain at least two unsaturated groups linking agent in the presence of carry out.
35. the polymerisate of claim 34, therein ethylene base comonomer comprises at least a hydrophobic comonomer.
36. the polymerisate of claim 35, wherein hydrophobic comonomer is selected from methyl methacrylate, TRIS, DSPMA and vinyl cyanide.
37. the polymerisate of claim 34, therein ethylene base comonomer comprises at least a hydrophilic monomer.
38. the polymerisate of claim 37, therein ethylene base comonomer is selected from hydroxyethyl methylacrylate, N-vinyl pyrrolidone, N,N-DMAA, (methyl) vinylformic acid, dihydroxypropyl methacrylate and acrylamide.
39. the polymerisate of claim 34, therein ethylene base comonomer comprise at least a hydrophobicity and at least a hydrophilic polymerized monomer.
40. the polymerisate of claim 34, this polymerisate can be in the presence of the linking agents that contains two unsaturated groups at least, obtained by each the further polymerization of polymerizable unsaturated group of multipolymer of claim 1 to 32.
41. the polymerisate of claim 34 comprises at least a vinyl comonomer and at least a linking agent.
42. one kind mainly comprises each the moulded product of polymerisate of claim 34 to 41.
43. the moulded product of claim 42, this moulded product are the Ophthalmoligic instrument that vision correction is used.
44. the moulded product of claim 42, this moulded product are contact lens.
45. the moulded product of claim 44, this moulded product are aqueous soft-contact lens.
46. the moulded product of claim 44, this moulded product are the contact lens low water content deflection, ventilation property (RGP).
47. the moulded product of claim 44, this moulded product are high oxygen permeability, can wear the lens of longer time that it has good water-permeable and good eye is gone up movability.
48. the contact lens of claim 47, based on the gross weight of lens, the whole water content of these lens is 5～30 weight %, preferred 10～20 weight %, particularly 10～15 weight %.
49. the moulded product of claim 42, this moulded product are ophthalmic lens.
50. the moulded product of claim 42, this moulded product are lens cornea implant (cornea,artificial).
51. one kind mainly comprises each the biomedical articles of polymerisate of claim 34 to 41.
52. each the application of multipolymer in the coated articles surface of claim 1 to 32.
53. each the application of polymerisate in the coated articles surface of claim 34 to 41.
54. each multipolymer of claim 1 to 32 is in the application of preparation in the moulded product.
55. each multipolymer of claim 1 to 32 is in the application of preparation in the contact lens.
CN 97195876 1996-06-27 1997-06-19 Amphiphilic, segmented copolymer of controlled morphology and ophthalmic devices including contact lenses made therefrom Pending CN1223673A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 97195876 CN1223673A (en) 1996-06-27 1997-06-19 Amphiphilic, segmented copolymer of controlled morphology and ophthalmic devices including contact lenses made therefrom

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/671,278 1996-06-27
CN 97195876 CN1223673A (en) 1996-06-27 1997-06-19 Amphiphilic, segmented copolymer of controlled morphology and ophthalmic devices including contact lenses made therefrom

Publications (1)

Publication Number Publication Date
CN1223673A true CN1223673A (en) 1999-07-21

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102498431A (en) * 2009-09-15 2012-06-13 诺瓦提斯公司 Prepolymers suitable for making ultra-violet absorbing contact lenses
CN102803999A (en) * 2009-06-16 2012-11-28 博士伦公司 Biomedical devices, polymeric materials and contact lenses comprising same
CN101454395B (en) * 2006-05-25 2013-04-10 阿科玛股份有限公司 Amphiphilic block copolymers
CN106716182A (en) * 2014-09-26 2017-05-24 诺华股份有限公司 Polymerizable polysiloxanes with hydrophilic substituents
CN107667133A (en) * 2015-03-24 2018-02-06 应用仿生学有限公司 The vesica and novel block copolymer formed by block copolymer

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101454395B (en) * 2006-05-25 2013-04-10 阿科玛股份有限公司 Amphiphilic block copolymers
CN102803999A (en) * 2009-06-16 2012-11-28 博士伦公司 Biomedical devices, polymeric materials and contact lenses comprising same
CN102803999B (en) * 2009-06-16 2014-11-12 博士伦公司 Biomedical devices
CN102498431A (en) * 2009-09-15 2012-06-13 诺瓦提斯公司 Prepolymers suitable for making ultra-violet absorbing contact lenses
CN106716182A (en) * 2014-09-26 2017-05-24 诺华股份有限公司 Polymerizable polysiloxanes with hydrophilic substituents
CN106716182B (en) * 2014-09-26 2020-06-12 爱尔康公司 Polymerizable polysiloxane with hydrophilic substituent
CN107667133A (en) * 2015-03-24 2018-02-06 应用仿生学有限公司 The vesica and novel block copolymer formed by block copolymer
CN107667133B (en) * 2015-03-24 2021-05-07 应用仿生学有限公司 Vesicles formed from block copolymer, and block copolymer

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