CN101977638A - Coating solutions comprising segmented interactive block copolymers - Google Patents

Coating solutions comprising segmented interactive block copolymers Download PDF

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Publication number
CN101977638A
CN101977638A CN2008801271855A CN200880127185A CN101977638A CN 101977638 A CN101977638 A CN 101977638A CN 2008801271855 A CN2008801271855 A CN 2008801271855A CN 200880127185 A CN200880127185 A CN 200880127185A CN 101977638 A CN101977638 A CN 101977638A
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block
surface
method
medical device
hydrophilic
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CN2008801271855A
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D·A··希普
D·P·范德比尔特
J·F·孔茨勒
J·G··林哈特
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博士伦公司
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Priority to US61/016,843 priority
Priority to US12/334,619 priority patent/US8100528B2/en
Priority to US12/334,619 priority
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Priority to PCT/US2008/086990 priority patent/WO2009085756A1/en
Publication of CN101977638A publication Critical patent/CN101977638A/en

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    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS, OR APPARATUS
    • G02B1/00Optical elements characterised by the material of which they are made
    • G02B1/04Optical elements characterised by the material of which they are made made of organic materials, e.g. plastics
    • G02B1/041Lenses
    • G02B1/043Contact lenses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/34Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G
    • C08J7/00Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/04Coating
    • C08J7/047Coating with only one layer of a composition containing a polymer binder
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09DCOATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D153/00Coating compositions based on block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers
    • C09D153/005Modified block copolymers
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G
    • C08J2333/00Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
    • C08J2333/04Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters
    • C08J2333/14Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
    • C08J2333/16Homopolymers or copolymers of esters containing halogen atoms
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G
    • C08J2383/00Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen, or carbon only; Derivatives of such polymers
    • C08J2383/10Block- or graft-copolymers containing polysiloxane sequences
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G
    • C08J2453/00Characterised by the use of homopolymers or copolymers, obtained by polymerisation reactions only involving carbon-to-carbon unsaturated bonds, not provided for in groups C08J2423/00 - C08J2453/00

Abstract

This invention is directed toward surface treatment of a device. The surface treatment comprises the attachment of interactive segmented block copolymers to the surface of the substrate by means of interactive functionalities of the segmented block copolymer reacting with complementary surface functionalities in monomeric units along the polymer substrate. The present invention is also directed to a surface modified medical device, examples of which include contact lenses, intraocular lenses, vascular stents, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, catheters, implants, and the like, comprising a surface made by such a method.

Description

包含相互作用的嵌段共聚物的涂覆溶液 Interaction of the coating solution containing the block copolymer

技术领域 FIELD

[0001] 本发明涉及包含新型特制聚合物的涂覆溶液,其可用作眼科器件的表面涂料。 [0001] The present invention relates to a novel coating solution comprising a special polymer, which are useful as ophthalmic devices of surface coatings. 这些聚合物可使用受控的自由基聚合方法进行特制,并含有许多功能区域。 These polymers may be used for controlled radical polymerization process specially, and contain a number of functional areas. 受控的自由基聚合使得可以很容易合成具有可调的化学组成的嵌段共聚物,其因此显示出与通过常规无自由基聚合制备的共聚物不同的化学性能。 Controlled radical polymerization makes it easy synthesis of block copolymers with tunable chemical composition, which thus exhibits no copolymer prepared by conventional free radical polymerization of different chemical properties. 具有包含官能团例如硼酸、氢键基团和静电基团的基底结合区域和亲水区域的嵌段共聚物在与含有互补官能团的基底相互结合时显示了良好的表面性能。 A block copolymer containing functional groups such as boronic acid base, hydrogen-bonding groups and electrostatic groups binding region and a hydrophilic region show good surface properties when combined with each other with the substrate containing a complementary functional group.

背景技术 Background technique

[0002] 医疗器件例如镜片由多种材料制备。 [0002] Medical devices such as lenses made from a variety of materials. 在隐形眼镜领域中,材料广泛地分为常规水凝胶或有机硅水凝胶。 In the contact lens field, the materials are widely divided into conventional hydrogels or silicone hydrogels. 最近,优选使用含有硅的材料(有机硅水凝胶)。 Recently, it is preferable to use a material containing silicon (silicone hydrogel). 这些材料在含水量上可能有很大的不同。 The material on the water content may be very different. 然而,不考虑其含水量如何,有机硅材料通常是相对疏水的、不可湿的,并且对脂质具有高亲和性。 However, irrespective of how the water content, silicone materials are generally relatively hydrophobic, non-wettable, and have a high affinity for lipids. 通过增加其亲水性和改善其生物相容性来改性有机硅器件的表面的方法是非常重要的。 By increasing their hydrophilicity and improving their biocompatibility to a surface of the modified silicone devices it is very important.

[0003] 已研究了许多用于表面涂覆的共聚物。 [0003] copolymers have been studied for many surface coating. 美国专利6,958,169披露了提供一种由包括亲水性形成器件用单体和第二形成器件用单体的单体混合物形成的医疗器件,所述亲水性形成器件用单体包含可共聚基团和给电子部分,所述第二形成器件用单体包含可共聚基团和相互作用的官能团;使该医疗器件的表面与湿润剂接触,所述湿润剂包括对所述第二形成镜片用单体提供的官能团具有反应性的给质子部分,并且与亲水性形成镜片用单体的给电子部分络合。 U.S. Patent No. 6,958,169 discloses providing a medical device formed from a monomer mixture comprising a hydrophilic device-forming monomer and a second device-forming monomer, the hydrophilic monomer forming device comprising a copolymerizable group and an electron donating portion, the second device-forming monomer containing a copolymerizable group and an interactive functional group; contacting surface of the medical device with a wetting agent, said wetting agent comprises a second a functional group to provide a lens a monomer having a reactive proton portion, and forming an electron lens portion complexed with a hydrophilic monomer. . .

[0004] 美国专利6,858,310公开了改性医疗器件的表面以增加其生物相容性或亲水性的方法,所述方法是用可去除的亲水聚合物通过所述亲水聚合物上的反应官能团与医疗器件表面上或表面附近互补的官能团反应对器件进行涂覆。 [0004] U.S. Patent No. 6,858,310 discloses a surface modification of a medical device to increase its biocompatibility or hydrophilicity of the method is the polymerization of a hydrophilic with a hydrophilic polymer can be removed by reactive functional groups reacts with the surface of the medical device on or near the surface functional groups complementary to the device is coated.

[0005] 美国专利6,599,559公开了改性医疗器件的表面以增加其生物相容性或亲水性的方法,所述方法是用可去除的亲水聚合物通过亲水聚合物上与医疗器件表面上或表面附近的反应官能团互补的反应官能团的反应对器件进行涂覆。 [0005] U.S. Patent No. 6,599,559 discloses a surface modification of a medical device to increase its biocompatibility or hydrophilicity, the method may be removed with a hydrophilic polymer by the hydrophilic polymer the reaction with the upper surface of the medical device at or near the surface of the reactive functional groups complementary to the reactive functional groups of the coating device.

[0006] 美国专利6,428,839公开了一种提高医疗器件的可润湿性的方法,所述方法包括以下步骤:(a)提供由包含亲水单体和含硅单体的单体混合物形成的医疗器件,其中所述医疗器件未经表面氧化处理;(b)使所述医疗器件的表面与含有给质子润湿剂的溶液接触,从而所述润湿剂在没有表面氧化处理步骤和不添加偶联剂的情况下与医疗器件表面上的亲水单体形成络合物。 [0006] U.S. Patent No. 6,428,839 discloses a method for improving the wettability of a medical device, the method comprising the steps of: (a) providing a monomer containing a hydrophilic monomer and a silicon-containing monomer the mixture formed a medical device, wherein the medical device without a surface oxidation treatment; (b) a surface of the medical device in contact with a solution containing a proton-donating wetting agent, so that no surface oxidation treatment step of a wetting agent and without the addition of a coupling agent forming a complex with the hydrophilic monomer on the surface of the medical device.

[0007] 当前许多共聚物均使用常规自由基聚合技术制备,聚合物的结构完全是无规的, 或者由各自单体的反应比例控制。 [0007] Many copolymers are currently made using conventional free radical polymerization techniques, the polymer structure is completely random or controlled by the reaction ratio of the respective monomers. 通过使用受控的自由基聚合技术,可以可控的方式形成共聚物,从而它们与使用常规自由基聚合技术制备的共聚物相比具有完全不同的溶液性能和涂覆性能。 By using controlled free radical polymerization techniques, the copolymer may be formed in a controlled manner, so that they in comparison with conventional free radical polymerization techniques copolymer prepared solutions having different properties and coating properties. 受控的自由基聚合可通过多种方法进行,例如ATRP (原子转移自由基聚合) 和RAFT (可逆加成断裂链转移聚合)。 Controlled radical polymerization may be carried out by various methods, such as ATRP (Atom Transfer Radical Polymerization) and the RAFT (reversible addition fragmentation chain transfer polymerization). 发明内容 SUMMARY

[0008] 根据本文公开的内容,本发明一般涉及用于在医疗器件的生产中形成结合涂层的包含相互作用的嵌段共聚物的涂覆溶液。 [0008] According to the disclosure herein, the present invention relates generally to forming coating solution comprising the block copolymer interaction of the bond coat in the production of medical devices. 本文所用术语“结合”是指相互作用的嵌段共聚物和器件表面官能团之间的各种化学相互作用例如静电、离子、络合、氢键或其它相互作用, 其使得涂料组合物与器件联系起来。 As used herein, the term "binding" refers to a variety of chemical interactions such as electrostatic, ionic, complexation, hydrogen bonding or other interactions between the block copolymer and the surface functional groups interacting device, which device makes contact with the coating composition stand up. 适合的器件的实例包括隐形眼镜、人工晶状体、人工晶状体插入器、血管支架、有晶体眼人工晶状体、无晶体眼人工晶状体、角膜植入物、导管、植入管等。 Examples of suitable devices include contact lenses, intraocular lenses, intraocular lens inserters, vascular stents, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, catheters, implants, and the like.

[0009] 根据本发明通过原子转移自由基聚合("ATRP")方法制备的相互作用的嵌段共聚物可具有下列通式(I): [0009] According to the present invention, by atom transfer radical polymerization ( "ATRP") block copolymer prepared by the process of interaction may have the following general formula (I):

[0010] Rr[(A)m]p-[(B)n]qX (I) [0010] Rr [(A) m] p - [(B) n] qX (I)

[0011] 其中礼是能够用作原子转移自由基聚合的引发剂的部分的反应性残基,A是化学结合单元嵌段,B是亲水单元嵌段,m是1到10,000,n是1到10,000,p和q是自然数,X 是原子转移自由基聚合的引发剂的卤素封端基团,其条件是当A是离子嵌段时,B将是非离子嵌段。 [0011] wherein Li is a reactive residue can be used as the atom transfer radical polymerization initiator moiety, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, X is a halogen atom transfer radical polymerization initiator capping group, with the proviso that when a is an ionic block, B will be a nonionic block. 应当注意的是,有许多方法用于在聚合后除去或转化原子转移自由基聚合引发剂的卤素封端基团,这对于本领域技术人员是已知的。 It should be noted that there are many methods for removing or converting the halogen atom in the polymerization capping group transfer radical polymerization initiator, which for the present are known to the skilled person. 因此,根据本发明使用ATRP制备的聚合物包括那些X是原子转移自由基聚合引发剂的卤素封端基团的聚合物和已经过聚合后除去或转化原子转移自由基聚合引发剂的卤素封端基团的那些聚合物(即衍生的反应产物)。 Accordingly, polymers prepared using ATRP according to the present invention include those wherein X is a halogen atom transfer radical polymerization of the polymer capping group of the initiator and the polymerization have been removed or transformed halogen-capping atom transfer radical polymerization initiator those groups of the polymer (i.e., derivatized reaction product). 含有卤素端基的聚合物可用于许多传统烷基卤有机反应中。 Polymers containing halogen end groups may be used in many traditional alkyl halide organic reactions. 在一个实施例中,在自由基来源(AIBN或Cu(I)络合物)存在下,向聚合烷基卤中添加三丁基甲锡烷产生饱和氢封端的聚合物。 In one embodiment, the free radical source (AIBN, or Cu (I) complex) is present, the alkyl halide is added to the polymerization tributyl stannyl produce saturated hydrogen-terminated polymer. 在另一个实施例中,通过用烯丙基三正丁基锡烷替换三丁基甲锡烷可制备具有烯丙基端基的聚合物。 In another embodiment, the polymer has an allyl end groups can be prepared by substituting tributyl stannyl with allyl tri-n-butyl stannane. 末端卤素也可通过亲核取代、自由基化学或路易斯酸催化的亲电加成被取代以产生多种遥爪衍生物,例如烯烃、炔烃、醇、硫醇、烷烃、叠氮化物、胺、磷鐺或环氧基等等。 Terminal halogen can also be substituted by nucleophilic, free radical chemistry, or electrophilic addition catalyzed by Lewis acids are substituted to produce a plurality of telechelic derivatives, such as alkenes, alkynes, alcohols, thiols, alkanes, azides, amines , phosphorus pan or an epoxy group and the like.

[0012] 根据本发明通过可逆加成断裂链转移聚合(“RAFT")方法制备的相互作用的嵌段共聚物可具有下列通式(II): [0012] According to the present invention, transfer polymerization by reversible addition fragmentation chain interactive segmented block copolymers prepared ( "RAFT") method may have the following general formula (II):

[0013] Rr[(A)m]p-[(B)n]q-R2 (II) [0013] Rr [(A) m] p - [(B) n] q-R2 (II)

[0014] 其中队是RAFT试剂或自由基引发剂的形成自由基的残基,A是化学结合单元嵌段,B是亲水单元嵌段,m是1到10,000,n是1到10,000,p和q是自然数,R2是链转移试剂的二硫酯嵌段,其条件是当A是离子嵌段时,B将是非离子嵌段。 [0014] radical in which teams are formed RAFT agent or free radical initiator residue, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is from 1 to 10 , 000, p and q are natural numbers, the chain transfer agent R2 is a thio carbonyl thio, with the proviso that when a is an ionic block, B will be a nonionic block. 基于二硫酯化学的RAFT 试剂是本领域技术人员公知的,包括例如黄原酸酯、三硫代碳酸酯和二硫代羧酸酯。 Ester-based disulfide chemistry RAFT agents are known to the skilled person, including, for example, xanthates, trithiocarbonates and dithio-carboxylate. 应当注意的是,本领域普通技术人员已知多种用于聚合后除去或转化链转移剂的二硫酯嵌段的方法。 It should be noted that those of ordinary skill in the art a variety of methods for post polymerization removal or transformation of dithio ester chain transfer agent block. 因此根据本发明使用RAFT试剂制备的聚合物包括其中R2是链转移试剂的二硫酯嵌段的那些,和那些已经过聚合后除去或转化链转移试剂的二硫酯嵌段的聚合物(即衍生的反应产物)。 Therefore polymers prepared using RAFT agent according to the present invention include those wherein R2 is a dithio ester chain transfer agent that blocks, and after the polymerization have been removed by conversion of the thio carbonyl thio polymer chain transfer agent or those (i.e. derivatized reaction product). 所述转化的一个实例是使用自由基还原剂用氢取代二硫酯基团。 Examples of the conversion of a radical reducing agent is hydrogen with a disulfide substituent ester group. 其它包括端基的热分解,或通过氨解作用将二硫酯基团转化为硫醇基团。 Other terminal groups including thermal decomposition, or by the ammonolysis dithio ester group into a thiol group. 可制备多种遥爪衍生物,例如烯烃、炔烃、醇、硫醇、烷烃、叠氮化物、胺、磷鐺或环氧基等。 It may be prepared by a variety of telechelic derivatives, such as alkenes, alkynes, alcohols, thiols, alkanes, azides, amines, phosphorus pan or an epoxy group.

[0015] 根据本发明通过可逆加成断裂链转移聚合(“RAFT")方法制备的相互作用的嵌段共聚物可具有下列通式(III):[0016] Rl-[(B)n]q-[(A)m]p-R2-[(A)m]p-[(B)n]q_Rl (III) Interactive segmented block copolymers prepared [0015] According to the present invention, by reversible addition fragmentation chain transfer polymerization ( "RAFT") method may have the following general formula (III): [0016] Rl - [(B) n] q - [(A) m] p-R2 - [(A) m] p - [(B) n] q_Rl (III)

[0017] 其中R1是RAFT试剂或自由基引发剂的形成自由基的残基,A是化学结合单元嵌段,B是亲水单元嵌段,m是1到10,000,n是1到10,000,p和q是自然数,R2是硫代羰基。 [0017] wherein R1 is a radical forming a RAFT agent or free radical initiator residue, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is from 1 to 10 , 000, p and q are natural numbers, R2 is a thiocarbonyl group.

[0018] 对于每个通式I、II和III的聚合物来说,嵌段单元的顺序并不重要,相互作用的嵌段共聚物可含有超过2个嵌段。 [0018] For each of Formulas I, II and III polymers, the order of the block units is not critical, the block copolymer may contain interacting more than two blocks. 因此该相互作用的嵌段共聚物可以是多嵌段共聚物,包括一个或多个嵌段的重复。 Thus the interaction of block copolymers may be multiblock copolymers, comprising one or more blocks of repeats. 参见下面非限制性的实例,它们均落于通式I、II和III中: See the following non-limiting examples, all of which fall within Formulas I, II and III:

[0019] (l)-(A)m(B)n- [0019] (l) - (A) m (B) n-

[0020] (2)-(B)n-(A)m- [0020] (2) - (B) n- (A) m-

[0021] (3)-(A)m-(B)n-(A)m- [0021] (3) - (A) m- (B) n- (A) m-

[0022] 根据本发明的相互作用的嵌段共聚物还可包含被认为是未结合的或不是亲水性的嵌段,例如聚苯乙烯或聚甲基丙烯酸甲酯。 [0022] The interactive segmented block copolymers of the present invention may be considered to comprise unbound or not hydrophilic block such as polystyrene or polymethyl methacrylate. 聚合物内非结合或非亲水性嵌段的存在也包括在所述相互作用的嵌段共聚物和本发明式I、II和III的范围内。 Non-binding or non hydrophilic block polymer is present in the block copolymer are also included in the formula of the present invention and the interaction of I, II and III within the scope.

[0023] 因此,在本发明的一些实施方案中公开了形成表面改性的医疗器件的方法,所述方法包括提供在至少一个表面上具有至少一个提供相互作用的官能团的基团的医疗器件; 提供包含相互作用的嵌段共聚物的表面改性剂,所述相互作用的嵌段共聚物包含亲水嵌段和具有与所述医疗器件至少一个提供反应性官能团的基团互补的反应性的化学结合单元嵌段;使医疗器件的具有相互作用的官能团的至少一个表面与所述表面改性剂接触;以及,使器件表面和表面改性剂处于适于在器件表面和表面改性剂之间形成化学相互作用的条件下,以形成表面改性的医疗器件,所述化学相互作用选自静电、离子、络合或氢键相互作用。 [0023] Accordingly, there is disclosed a method of forming a surface modified medical device, in some embodiments of the invention, the method comprising providing a medical device having at least one group of the functional group interaction provided on at least one surface; providing a surface modifying agent comprising a interactive segmented block copolymers, said block copolymer comprising a hydrophilic interaction block having reactivity with the medical device to provide at least one functional group reactive groups complementary to chemical binding unit block; making a medical device having a functional group interacting at least one surface in contact with the surface modifying agent; and, the device surface and surface modifying agent is adapted to the device surface and surface modifying agent in the under conditions of chemical interaction between the formation, to form a surface modified medical device, the selected chemical interaction of electrostatic, ionic, complexation or hydrogen bonding interactions.

[0024] 本发明在一些实施方案中还公开了表面改性的医疗器件,其包括在至少一个表面上具有至少一个提供反应性官能团的基团的医疗器件,以及用于医疗器件表面的包含亲水嵌段和化学结合单元嵌段的相互作用的嵌段共聚物;其中在所述器件的表面与表面改性剂之间发生化学相互作用,以形成表面改性的医疗器件,所述化学相互作用选自静电、离子、 络合或氢键相互作用。 [0024] In some embodiments, the present invention also discloses a surface modified medical device comprising a medical device having at least one group providing reactive functionality on at least one surface, and a surface of a medical device comprising a pro interaction and block copolymers of a block of the chemical binding unit block; wherein the chemical interaction between the surface modifier and the surface of the device, to form a surface modified medical device, the mutual chemical electrostatic effect is selected, ionic, complexation or hydrogen bonding interactions.

附图说明 BRIEF DESCRIPTION

[0025] 图1是用于制备嵌段共聚物的原子转移自由基聚合(ATRP)实例示意图,其中在聚合物的一端是化学结合单元的低聚嵌段,之后是大的亲水嵌段; [0025] FIG. 1 is a block copolymer preparation atom transfer radical polymerization (ATRP) a schematic example in which an end of a polymer is a chemical binding unit block of oligomerization, followed by a large hydrophilic block;

[0026] 图2是各种单体的结构式,它们可用于提供本发明嵌段共聚物的相互作用的官能团; [0026] FIG. 2 is a structural formula of various monomers which may be used to provide interaction between the functional group of the block copolymer of the present invention;

[0027] 图3是显示如何使用RAFT聚合来聚合具有功能性区域的嵌段共聚物的反应流程图。 [0027] FIG. 3 is a flowchart showing how RAFT polymerization reaction of the block copolymer having a polymerized functional areas.

具体实施方式 Detailed ways

[0028] 本发明一般涉及包含相互作用的嵌段共聚物的涂覆溶液。 [0028] The present invention relates generally to coating solutions comprising interaction block copolymer. 包含相互作用的嵌段共聚物的组合物可用于在生产医疗器件中提供表面结合的涂层。 Interaction compositions comprising block copolymers useful in providing surface bound coatings in the manufacture of medical devices. 在优选的实施方案中,本发明涉及具有与医疗器件例如镜片的表面官能团互补的相互作用的官能团的相互作用的嵌段共聚物。 In a preferred embodiment, the present invention relates to a block copolymer having a medical device to interact with the lens such as surface functional group complementary to the functional group interaction. 应当理解的是,术语“表面”不限于“至少一个完整表面”。 It should be understood that the term "surface" is not limited to "at least one complete surface." 表面覆盖不需要均勻或完整以对表面官能团有效。 Need not uniform or complete surface coverage of the effective surface functional groups. 本发明的相互作用的嵌段共聚物可用作生物相容材料的涂层,所述生物相容材料包括通常用于镜片,包括隐形眼镜的软性和刚性材料。 Block copolymers of the present invention are useful interaction coating of biocompatible material, the biocompatible material comprises generally a lens and a soft contact lens comprising a rigid material.

[0029] 根据本发明通过原子转移自由基聚合(“ATRP")方法制备的相互作用的嵌段共聚物可具有下列通式(I): [0029] According to the present invention, by atom transfer radical polymerization ( "ATRP") block copolymer prepared by the process of interaction may have the following general formula (I):

[0030] Rr[(A)m]p-[(B)n]qX (1) [0030] Rr [(A) m] p - [(B) n] qX (1)

[0031] 其中礼是能够用作原子转移自由基聚合引发剂的部分的反应性残基,A是化学结合单元嵌段,B是亲水单元嵌段,m是1到10,000,n是1到10,000,p和q是自然数,X是原子转移自由基聚合引发剂的卤素封端基团,其条件是当A是离子嵌段时,B将是非离子嵌段。 [0031] where Li is the atom transfer radical polymerization can be used as the reaction initiator agent residue moiety, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is 1 to 10,000, p and q are natural numbers, X is a halogen atom transfer radical polymerization initiator capping group, with the proviso that when a is an ionic block when, B will be a nonionic block. 本领域技术人员会意识到X为烷基卤时可通过随后的化学反应转化成另一种官能团。 Those skilled in the art will appreciate that when X is an alkyl halide may be converted to another functionality through subsequent chemical reaction. 应当注意的是,有许多方法用于在聚合后除去或转化原子转移自由基聚合引发剂的卤素封端基团,这对于本领域技术人员是已知的。 It should be noted that there are many methods for removing or converting the halogen atom in the polymerization capping group transfer radical polymerization initiator, which for the present are known to the skilled person. 因此,根据本发明使用ATRP制备的聚合物包括那些X是原子转移自由基聚合引发剂的卤素封端基团的聚合物和已经过聚合后除去或转化原子转移自由基聚合引发剂的卤素封端基团的那些聚合物(即衍生的反应产物)。 Accordingly, polymers prepared using ATRP according to the present invention include those wherein X is a halogen atom transfer radical polymerization of the polymer capping group of the initiator and the polymerization have been removed or transformed halogen-capping atom transfer radical polymerization initiator those groups of the polymer (i.e., derivatized reaction product). 含有卤素端基的聚合物可用于许多传统烷基卤有机反应中。 Polymers containing halogen end groups may be used in many traditional alkyl halide organic reactions. 在一个实施例中,在自由基来源(AIBN或Cu(I)络合物)存在下,向聚合烷基卤中添加三丁基甲锡烷产生饱和氢封端的聚合物。 In one embodiment, the free radical source (AIBN, or Cu (I) complex) is present, the alkyl halide is added to the polymerization tributyl stannyl produce saturated hydrogen-terminated polymer. 在另一个实施例中,通过用烯丙基三正丁基锡烷替换三丁基甲锡烷可制备具有烯丙基端基的聚合物。 In another embodiment, the polymer has an allyl end groups can be prepared by substituting tributyl stannyl with allyl tri-n-butyl stannane. 末端的卤素也可通过亲核取代、自由基化学或路易斯酸催化的亲电加成被取代以产生多种遥爪衍生物,例如烯烃、炔烃、醇、硫醇、烷烃、叠氮化物、胺、磷鐺或环氧基等。 Halogen-terminus may be substituted by nucleophilic, free radical chemistry, or electrophilic addition catalyzed by Lewis acid to produce a wide variety of telechelic substituted derivatives, such as alkenes, alkynes, alcohols, thiols, alkanes, azides, amines, phosphorus pan or an epoxy group.

[0032] 根据本发明通过可逆加成断裂链转移聚合(“RAFT")方法制备的相互作用的嵌段共聚物具有下列通式(II): [0032] According to the present invention having the following general formula by reversible addition fragmentation chain transfer polymerization of interactive segmented block copolymers prepared ( "RAFT") Method (II):

[0033] Rr[(A)m]p-[(B)n]q-R2 (II) [0033] Rr [(A) m] p - [(B) n] q-R2 (II)

[0034] 其中礼是RAFT试剂或自由基引发剂的形成自由基的残基,A是化学结合单元嵌段,B是亲水单元嵌段,m是1到10,000,n是1到10,000,p和q是自然数,R2是链转移试剂的二硫酯嵌段,其条件是当A是离子嵌段时,B将是非离子嵌段。 [0034] where Li is a RAFT agent or free radical initiator radical forming agent residue, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is from 1 to 10 , 000, p and q are natural numbers, the chain transfer agent R2 is a thio carbonyl thio, with the proviso that when a is an ionic block, B will be a nonionic block. 本领域技术人员会意识到,R2为二硫酯嵌段时可通过随后的化学反应从聚合物末端断裂,或转化为另一种官能团。 Those skilled in the art will recognize, the reaction may be cleaved from R2 by subsequent chemical polymer end when the thio carbonyl thio, or converted to another functional group. 基于二硫酯化学的RAFT试剂是本领域普通技术人员公知的,包括例如黄原酸酯、三硫代碳酸盐和二硫代羧酸酯。 Ester-based disulfide chemistry RAFT agents are known to those of ordinary skill in the art, including, for example, xanthates, trithiocarbonates and dithio-carboxylate. 应当注意的是,本领域普通技术人员已知多种用于聚合后除去或转化链转移试剂的二硫酯嵌段的方法。 It should be noted that those of ordinary skill in the art a variety of methods to remove or convert disulfide chain transfer agent for polymerization of the acrylate block. 因此根据本发明使用RAFT试剂制备的聚合物包括其中R2是链转移试剂的二硫酯嵌段的那些聚合物,和那些已经过聚合后除去或转化链转移试剂的二硫酯嵌段的聚合物(即衍生的反应产物)。 Therefore polymers prepared using RAFT agent according to the present invention include those wherein R2 is a polymer chain transfer agent dithioesters blocks, and that after the polymerization have been removed or dithio ester chain transfer agent conversion block polymer (i.e., derivatized reaction product). 所述转化的一个实例是使用自由基还原剂用氢取代二硫酯基团。 Examples of the conversion of a radical reducing agent is hydrogen with a disulfide substituent ester group. 其它包括末端基团的热分解,或通过氨解作用将二硫酯基团转化为硫醇基团。 Other terminal groups include thermal decomposition, or by the ammonolysis dithio ester group into a thiol group. 可制备多种遥爪衍生物,例如烯烃、炔烃、醇、硫醇、烷烃、叠氮化物、胺、磷鐺或环氧基等。 It may be prepared by a variety of telechelic derivatives, such as alkenes, alkynes, alcohols, thiols, alkanes, azides, amines, phosphorus pan or an epoxy group.

[0035] 根据本发明通过可逆加成断裂链转移聚合(“RAFT")方法制备的相互作用的嵌段共聚物具有下列通式(III): [0035] having the following formula (III) according to the invention by reversible addition fragmentation chain transfer polymerization of interactive segmented block copolymers prepared ( "RAFT") Method:

[0036] Rl-[(B)n]q-[(A)m]p-R2-[(A)m]p-[(B)n]q_Rl (III) [0036] Rl - [(B) n] q - [(A) m] p-R2 - [(A) m] p - [(B) n] q_Rl (III)

[0037] 其中R1是RAFT试剂或自由基引发剂的形成自由基的残基,A是化学结合单元嵌段,B是亲水单元嵌段,m是1到10,000,n是1到10,000,p和q是自然数,R2是二硫酯基团。 [0037] wherein R1 is a radical forming a RAFT agent or free radical initiator residue, A is a chemical binding unit block, B is a hydrophilic unit block, m is 1 to 10,000, n is from 1 to 10 , 000, p and q are natural numbers, R2 is a thio ester group.

8[0038] 对于每个通式I、II和III的聚合物来说,嵌段单元的顺序并不重要,相互作用的嵌段共聚物可含有超过2个的嵌段。 8 [0038] I II and III for each of the polymers of the general formula, the order of the block units is not critical and may interact with the block copolymer block comprising more than two. 因此该相互作用的嵌段共聚物可以是多嵌段共聚物, 包括一个或多个嵌段的重复。 Thus the interaction of block copolymers may be multiblock copolymers, comprising one or more blocks of repeats. 可参见下面非限制性的实例,其均落于通式I、II和III中: See the following non-limiting examples, each of which fall within Formulas I, II and III:

[0039] (l)-(A)m(B)n- [0039] (l) - (A) m (B) n-

[0040] (2)-(B)n-(A)m- [0040] (2) - (B) n- (A) m-

[0041] (3)-(A)m-(B)n-(A)m- [0041] (3) - (A) m- (B) n- (A) m-

[0042] 根据本发明的相互作用的嵌段共聚物还可包含被认为是非结合的或非亲水性的嵌段,例如聚苯乙烯或聚甲基丙烯酸甲酯。 [0042] are considered non-binding may further comprise a hydrophilic block or non-block copolymers according to the present invention, the interaction of, for example, polystyrene or polymethyl methacrylate. 聚合物内非结合或非亲水性嵌段的存在也包括在所述相互作用的嵌段共聚物和本发明式I、II和III的范围内。 Non-binding or non hydrophilic block polymer is present in the block copolymer are also included in the formula of the present invention and the interaction of I, II and III within the scope.

[0043] 本发明提供了可通过使用互补性相互作用的官能团用于表面改性隐形眼镜等医疗器件的材料。 [0043] The present invention provides a material through the use of complementary functional groups for the interaction of the surface modification of contact lenses and other medical devices. 尽管下文中仅以隐形眼镜为例进行说明,其不应当认为是限制性的,因为除隐形眼镜外,本发明的方法还适用于表面改性其它医疗器件,例如有晶体眼和无晶体眼人工晶状体以及角膜植入物。 Hereinafter Although only contact lenses will be described as an example, which should not be considered limiting, since in addition to contact lenses, the method of the present invention is also applicable to surface modification of other medical devices such as phakic and aphakic intraocular lens and corneal implant. 隐形眼镜和其它生物医学器件的聚合物材料的表面相互作用的基团被用于与本发明的反应性嵌段共聚物形成化学连接,即结合。 Interaction of surface groups of the polymer material, contact lenses and other biomedical devices are used to form a chemical connection with the reaction of the block copolymer of the present invention, i.e., binding. 本发明中优选的相互作用的嵌段共聚物基于要涂覆的聚合物材料的特定的相互作用的表面基团来选择。 Block copolymers of the present invention is based on the interaction of preferred materials to be coated polymer surface groups to select a specific interaction. 根据本发明,选择用于表面改性的一种或多种相互作用的嵌段共聚物应当具有与所述基底的表面互补的相互作用的化学官能团。 According to the present invention, a surface-modifying selected for the interaction of one or more block copolymers should have a chemical functionality group capable of interacting with a complementary surface of the substrate. 所述互补的相互作用的化学官能团使得在相互作用的嵌段共聚物和基底的互补表面官能团之间能发生化学反应,以形成静电、离子、络合、氢键或其它相互作用。 The interaction of the complementary chemical functionality enables a chemical reaction between the complementary surfaces of the base block copolymer and a functional group interacting to form an electrostatic, ionic, complexation, hydrogen bonding or other interactions. 因此所述一种或多种相互作用的嵌段共聚物结合到隐形眼镜等医疗器件的表面,实现其表面改性。 Thus the interaction of the one or more block copolymer bonded to the surface of contact lenses and other medical devices, to achieve surface modification thereof.

[0044] 相互作用的嵌段共聚物包括化学结合单元嵌段以提供所需的分子的表面结合。 [0044] Interaction block copolymers include chemical binding unit block to provide the desired surface molecule binding. 所述化学结合单元嵌段可以不同,基于相互作用的嵌段共聚物的用途而定。 The chemical binding unit block may be different, based on the use of the interaction of the block copolymer may be. 也就是说,选择相互作用的嵌段共聚物的化学结合单元嵌段以提供与器件的表面官能团互补的官能团。 That is, the interactive segmented block copolymers selected chemical binding unit block surface functional groups to provide functional groups with a complementary device. 化学结合单元嵌段将包含诸如硼酸、氢键基团和静电基团的官能团。 Chemical binding unit block containing a functional group such as a boronic acid, hydrogen-bonding groups and electrostatic groups.

[0045] 所述嵌段共聚物的化学结合单元单体根据器件表面的官能团进行选择。 The [0045] The chemical binding unit monomer of the block copolymer is selected depending on the functional groups of the device surface. 例如,如果器件表面的相互作用的分子含有羧酸基团,相互作用的嵌段共聚物的化学结合单元单体可以是含季铵的单体。 For example, if the molecular interaction of the surface of the device contains a carboxylic acid group, a block copolymer of chemical interaction may be a binding unit monomer containing a quaternary ammonium monomer. 如果器件表面的相互作用的分子含有羟基或氨基官能团,相互作用的嵌段共聚物的化学结合单元单体可以是含硼酸的单体。 If the surface of the device interacting molecules containing hydroxyl or amino functional groups, chemical interaction binding unit monomer of the block copolymer may be a boric acid-containing monomers. 多种与器件表面的相互作用基团互补的化学结合单元的含官能团单体的适当组合对于本领域技术人员将是明显的。 Interaction more groups of the device surface of the chemical binding unit complementary to an appropriate combination of functional group-containing monomer skilled in the art will be apparent. 例如, 所述化学结合单元嵌段可包含选自苯乙烯硼酸、3-甲基丙烯酰氨基苯乙烯硼酸、三甲基、 2-甲基丙烯酰氧基乙基磺酸盐、3-甲基丙烯酰氨基丙基-N,N,N-三甲基铵盐、2-甲基丙烯酰氧基乙基-N,N, N-三甲基铵盐和含胺单体例如3-甲基丙烯酰氨基丙基-N,N- 二甲胺的部分。 For example, the chemical binding unit block may comprise a borate selected from styrene, styrene-acrylamido-3-boronic acid, trimethyl, 2-methacryloyloxyethyl sulfonate, 3-methyl acrylamido propyl -N, N, N- trimethylammonium salt, 2-methacryloyloxyethyl -N, N, N- trimethyl ammonium salts and amine containing monomers such as 3-methyl acrylamido propyl -N, N- dimethylamine portion. 表1中列出了互补性官能团的例子。 Table 1 lists Examples of complimentary functional groups.

[0046] 表1[0047] [0046] Table 1 [0047]

Figure CN101977638AD00101

[0048] 所述相互作用的嵌段共聚物的化学结合单元嵌段是低聚物或多聚物,调节其大小以提供与要涂覆的医疗器件表面的适当结合。 [0048] The interaction of the chemical binding unit block of the block copolymer is an oligomer or polymer, adjusting the size of the medical device to provide a surface to be coated appropriately combined. 因此,式I、II或III的变量m可以为1至约1000,优选为1至约100,最优选为1至约30。 Thus, Formula I, II or III may be variable m is 1 to about 1000, preferably from 1 to about 100, and most preferably from 1 to about 30.

[0049] 除化学结合单元外,本发明的相互作用的嵌段共聚物还含有亲水区域,当嵌段共聚物与含有互补官能团的基底共价结合时显示良好的表面性质。 [0049] In addition to the chemical binding unit, interactions of the block copolymer of the present invention further contains a hydrophilic region, when the block copolymer containing a complementary functional group of a substrate covalently bound display good surface properties. 亲水区域包含至少一个亲水单体,例如HEMA、甲基丙烯酸甘油酯、甲基丙烯酸(“MAA")、丙烯酸(“AA")、甲基丙烯酰胺、丙烯酰胺、N,N' -二甲基甲基丙烯酰胺或N,N' -二甲基丙烯酰胺;其共聚物;亲水性预聚物,例如烯键式不饱和聚环氧烷烃、环内酰胺例如N-乙烯基-2-吡咯烷酮(“NVP"),或其衍生物。 The hydrophilic region comprises at least one hydrophilic monomer such as HEMA, glycerol methacrylate, methacrylic acid ( "MAA"), acrylic acid ( "AA"), methacrylamide, acrylamide, N, N '- two methyl acrylamide or N, N '- dimethyl acrylamide; copolymers thereof; hydrophilic prepolymers, such as ethylenically unsaturated polyalkylene oxide, cyclic lactams such as N- vinyl-2- - pyrrolidone ( "NVP"), or derivatives thereof. 其它实例有亲水性碳酸乙烯酯或氨基甲酸乙烯酯单体。 Other examples are the hydrophilic vinyl carbonate or vinyl carbamate monomers. 亲水性单体可以是非离子单体,例如甲基丙烯酸2-羟乙基酯(〃 HEMA" )、2_羟乙基丙烯酸酯(〃 HEA" )、2-(2_乙氧基乙氧基)乙基(甲基)丙烯酸酯、(甲基)丙烯酸甘油酯、聚(乙二醇(甲基)丙烯酸酯)、四氢呋喃(甲基)丙烯酸酯、(甲基)丙烯酰胺、N,N' -二甲基甲基丙烯酰胺、N,N' -二甲基丙烯酰胺(〃 DMA" )、N-乙烯基-2-吡咯烷酮(或其它N-乙烯基内酰胺)、N-乙烯基乙酰胺及其组合。亲水性单体的其它实例有美国专利5,070, 215中公开的碳酸乙烯酯和氨基甲酸乙烯酯单体,以及美国专利4,910,277中公开的亲水性噁唑酮单体。所述亲水性单体还可以是阴离子单体,例如2-甲基丙烯酰氧基乙磺酸盐。也可使用例如来自丙烯酸和甲基丙烯酸的取代的阴离子亲水性单体,其中取代基团可通过温和的化学过程除去。所述取代的阴离子亲水性单体的非限制性 Hydrophilic monomers can be nonionic monomers, such as methacrylic acid 2-hydroxyethyl acrylate (〃 HEMA "), 2_-hydroxyethyl acrylate (〃 HEA"), 2- (2_ ethoxyethoxy yl) ethyl (meth) acrylate, (meth) acrylate, poly (ethylene glycol (meth) acrylate), tetrahydrofuran (meth) acrylates, (meth) acrylamide, N, N '- dimethyl methacrylamide, N, N' - dimethylacrylamide (〃 DMA "), N- vinyl-2-pyrrolidone (or other N- vinyl lactams), N- vinylacetamide amides, and combinations thereof. other examples of hydrophilic monomers include U.S. Patent No. 5,070, 215 disclosed ethylene carbonate and vinyl carbamate monomers, hydrophilic and evil disclosed in U.S. Patent No. 4,910,277 oxazolone monomers. the hydrophilic monomers can also be anionic monomers such as 2-methacryloyloxyethyl sulfonate may also be used, for example from acrylic acid and methacrylic acid substituted anionic hydrophilic non-limiting monomers wherein the substituent group may be removed by mild chemical processes. the substituted anionic hydrophilic monomers 例包括(甲基)丙烯酸的三甲基硅烷基酯,其被水解以再生阴离子羧基。所述亲水性单体也可以是选自下列组中的阳离子单体:3_甲基丙烯酰氨基丙基-N,N,N-三甲基铵盐、2-甲基丙烯酰氧基乙基-N,N,N-三甲基铵盐、以及含胺的单体例如3-甲基丙烯酰氨基丙基-N,N-二甲基胺。其它合适的亲水性单体对于本领域技术人员是显而易见的。 Examples include (meth) acrylic acid trimethylsilyl ester, which is hydrolyzed to regenerate an anionic carboxyl groups of the hydrophilic monomer may be a cationic monomer selected from the following group: 3_ methacryloylamino propyl -N, N, N- trimethylammonium salt, 2-methacryloyloxyethyl -N, N, N- trimethyl ammonium salts, and amine-containing monomers such as 3-methacryloxypropyltrimethoxysilane amidopropyl -N, N- dimethylamine. other suitable hydrophilic monomers will be apparent to those skilled in the art.

[0050] 将调节亲水性单体嵌段的大小以提供所述相互作用的嵌段共聚物所需的表面涂覆性能。 [0050] The properties of the coated surface adjust the size of the hydrophilic monomer block of the block copolymer to provide the desired interaction. 亲水性低聚或高聚嵌段的大小根据要涂覆的基底和用途而可能不同。 The size of the hydrophilic oligomeric or high polymer blocks may vary depending on the substrate to be coated and use. 因此式I、 II或III的变量n可以为1至约10000,优选为约10至约1000,更优选为约20至约300。 Thus the formula I, II or III may be variable n is 1 to about 10,000, preferably from about 10 to about 1000, more preferably from about 20 to about 300.

[0051] 可使用原子转移自由基聚合(ATRP)制备嵌段共聚物,其中各嵌段和整个聚合物的分子量可精确地控制。 [0051] using atom transfer radical polymerization (ATRP) to prepare block copolymers wherein the molecular weight of each block and the entire polymer can be precisely controlled. 如图1所示,可使用原子转移自由基聚合(ATRP)制备嵌段共聚物, 其中在聚合物的一端有化学结合单元嵌段,随后是大亲水嵌段。 1, using atom transfer radical polymerization (ATRP) to prepare block copolymers in which one end of the polymer with a chemical binding unit block, followed by a large hydrophilic block. 应当理解的是,添加包含化学结合单元区域的单体和包含亲水区域的单体的顺序并不重要。 It will be appreciated that the addition of the monomer comprising the chemical binding unit monomer of the sequence and the region containing hydrophilic regions is not important. 多种单体可用于组配聚合物(例如参见图2)。 More monomers may be used to combine a polymer (e.g., see FIG. 2). 可使用可逆加成断裂链转移聚合(RAFT)制备嵌段共聚物,其中各嵌段和整个聚合物的分子量可精确地控制(参见图3)。 Using reversible addition fragmentation chain transfer polymerization (RAFT) preparing block copolymers, wherein the molecular weight of each block and the entire polymer can be precisely controlled (see FIG. 3).

[0052] 本发明的相互作用的嵌段共聚物可用于涂覆基底。 [0052] The interactive segmented block copolymers of the invention can be used to coat the substrate. 可用于本发明的基底材料的实例见Kunzler等的美国专利5,908,906 ;Kunzler等的5,714,557 ;Kunzler等的5,710,302 ;Lai 等的5,708,094 ;Bambury 等的5,616,757 ;Bambury 等的5,610,252 ;Lai 等的5,512,205 ;Lai 等的5,449,729 ;Kunzler 等的5,387,662 ;Lai 等的5,310,779 和Kunzler 等的6,891,010。 U.S. Patent No. instance be a base material of the present invention, see Kunzler like 5,908,906; Kunzler like 5,714,557; Kunzler like 5,710,302; Lai like 5,708,094; Bambury et the 5,616,757; Bambury like 5,610,252; Lai like 5,512,205; Lai like 5,449,729; Kunzler like 5,387,662; Lai like 5,310, 779 and Kunzler, etc. 6,891,010.

[0053] 本发明涉及相互作用的嵌段共聚物在医疗器件,包括“硬”和“软”隐形眼镜中的用途。 [0053] The present invention relates to the interaction of the block copolymer in the medical device, including the "hard" and "soft" contact lens use. 如上文所述,本发明可用于多种材料。 As described above, the present invention can be used in a variety of materials. 水凝胶通常是一类公知的材料,其包含水合的、平衡态下含水的交联聚合体系。 Hydrogels generally are a class of known materials, which comprises hydrated, crosslinked polymeric systems containing water at equilibrium. 含硅水凝胶含水量通常超过约5重量%,更通常为约10-约80重量%。 Silicon-containing hydrogels the water content is usually more than about 5 wt%, more typically from about 10 to about 80 wt%. 这样的材料通常通过聚合含有至少一种含硅单体和至少一种亲水性单体的混合物来制备。 Such materials are typically prepared by the mixture of at least one silicon-containing monomer and at least one hydrophilic monomer by polymerizing. 通常,含硅单体或亲水性单体用作交联剂(交联剂定义为具有多种可聚合官能团的单体)或者可使用单独的交联剂。 Typically, silicon-containing monomer or the hydrophilic monomer as a crosslinking agent (a crosslinker being defined as a monomer having multiple polymerizable functionalities) or a separate crosslinker may be used. 适用于形成含硅水凝胶的含硅单体单元是本领域已知的,美国专利4,136,250,4, 153,641,4, 740,533,5, 034,461,5, 070,215,5, 260,000、 5,310,779和5,358,995中提供了众多的实例。 Silicon-containing monomer unit is adapted to form a silicon containing hydrogels are known in the art, U.S. Patent No. 4,136,250,4, 153,641,4, 740,533,5, 034,461,5, 070 , 215,5, 260,000, 5,310,779 and 5,358,995 provides a number of examples.

[0054] 适用的含硅单体单元的实例包括大体积聚硅氧烷基烷基(甲基)丙烯酸单体。 [0054] Examples of applicable silicon-containing monomeric units include bulky polysiloxanylalkyl alkyl (meth) acrylic monomer. 大体积聚硅氧烷基烷基(甲基)丙烯酸单体的实例由下式IV表示: Alkyl bulky polysiloxanylalkyl (meth) acrylic monomer represented by the following formula Example IV:

[0055] [0055]

Figure CN101977638AD00111

[0056]其中,X 表示-0-或-NR-; [0056] wherein, X represents -0- or -NR-;

[0057] 各个礼独立地表示氢或甲基; [0057] Li each independently represent hydrogen or methyl;

[0058] 各个R2独立地表示低级烷基、苯基或由下式表示的基团, [0058] each R2 independently denotes a lower alkyl group, a phenyl group or a group represented by the formula,

[0059] [0059]

Figure CN101977638AD00121

[0060] 其中各个R' 2独立的表示低级烷基或苯基;以及h是1-10。 [0060] wherein each R '2 independently represent a lower alkyl or phenyl; and h is 1-10.

[0061] 一些优选的大体积单体是甲基丙烯酰氧丙基三(三甲基硅烷氧基)硅烷或三(三甲基硅烷氧基)硅烷基丙基甲基丙烯酸酯,有时称为TRIS。 [0061] Some preferred bulky monomers are methacryloxypropyl tris (trimethylsiloxy) silane or tris (trimethylsiloxy) silylpropyl methacrylate, sometimes referred to as TRIS.

[0062] 另一类代表性的含硅单体包括含硅的碳酸乙烯酯或氨基甲酸乙烯酯单体,例如1, 3-双[4-乙烯基氧羰基氧)丁基]四甲基二硅氧烷;3-(三甲基硅烷基)丙基乙烯基碳酸酯;3-(乙烯基氧羰基硫代)丙基]_[三(三甲基硅烷氧基)硅烷]、3-[三(三甲基硅烷氧基)硅烷基]丙基乙烯基氨基甲酸酯、3-[三(三甲基硅烷氧基)硅烷基]丙基烯丙基氨基甲酸酯;3-[三(三甲基硅烷氧基)硅烷基]丙基乙烯基碳酸酯;叔丁基二甲基硅烷氧基乙基乙烯基碳酸酯;三甲基硅烷基乙基乙烯基碳酸酯和三甲基硅烷基甲基乙烯基碳酸酯。 [0062] Another class of representative silicon-containing monomers includes silicon containing vinyl carbonate or vinyl carbamate monomers, e.g., 1,3-bis [4-vinyl-oxycarbonyl-yloxy) butyl] tetramethyl silicone; 3- (trimethylsilyl) propyl vinyl carbonate; 3- (vinyloxy carbonyl thio) propyl] _ [tris (trimethylsiloxy) silane], 3- [ tris (trimethylsiloxy) silyl] propyl vinyl carbamate, 3- [tris (trimethylsiloxy) silyl] propyl allyl carbamate; 3- [tris (trimethylsiloxy) silyl] propyl vinyl carbonate; tert-butyldimethylsilyloxy ethyl vinyl carbonate; trimethylsilanyl ethyl vinyl carbonate and trimethylsilane methyl vinyl carbonate.

[0063] 含硅的碳酸乙烯酯或氨基甲酸乙烯酯单体的实例由式V所示: [0063] Examples shown by Formula V silicon-containing vinyl carbonate or vinyl carbamate monomers:

[0064] [0064]

Figure CN101977638AD00122

[0065]其中: [0065] wherein:

[0066] V 代表-0-、-S-或-NH-; [0066] V representative of -0 -, - S- or -NH-;

[0067] RSi代表含硅的有机基团; [0067] RSi representative of a silicon-containing organic group;

[0068] R3代表氢或甲基; [0068] R3 represents hydrogen or methyl;

[0069] d为1、2、3或4 ;并且q是0或1。 [0069] d is 3 or 4; and q is 0 or 1.

[0070] 适当的含硅有机基团RSi包括下列基团 [0070] suitable silicon-containing organic group include the following groups RSi

[0071] -(CH2)n, Si[(CH2)m' CH3]3 ; [0071] - (CH2) n, Si [(CH2) m 'CH3] 3;

[0072] _(CH2)n, Si[0Si(CH2)m' CH3]3 ; [0072] _ (CH2) n, Si [0Si (CH2) m 'CH3] 3;

[0073] [0073]

Figure CN101977638AD00123

[0074] 以及 [0074] and

Figure CN101977638AD00131

[0076] 其中,R4代表 [0076] wherein, R4 representatives

[0077] [0077]

Figure CN101977638AD00132

[0078]其中p'是1-6; [0078] wherein p 'is 1-6;

[0079] R5代表具有1-6个碳原子的烷基或氟代烷基; [0079] R5 represents an alkyl group or a fluoroalkyl group having 1 to 6 carbon atoms;

[0080] e 是l_200;n'是1、2、3 或4 ;并且m,是0、1、2、3、4 或5。 [0080] e is l_200; n 'is 2, 3 or 4; and m, is 3, 4 or 5.

[0081] [0082] [0081] [0082]

式V的一个具体例子用式VI表示 A specific example of formula V represented by formula VI

Figure CN101977638AD00133

[0083] 另一类含硅单体包括聚氨酯_聚硅氧烷大分子单体(有时也指预聚物),其可如传统的聚氨酯弹性体一样具有硬-软-硬嵌段。 [0083] Another class of silicon-containing monomers includes polyurethane _ polysiloxane macromer (sometimes also referred prepolymers), which may have hard as conventional polyurethane elastomers as - Soft - Hard block. 它们可用亲水性单体例如HEMA封端。 They may be hydrophilic monomers such as HEMA terminated. 这样的含硅聚氨酯的实例公开于多个出版物中,包括Lai,Yu-Chin,“ The Role of Bulky Polysiloxanylalkyl Methacryates in Polyurethane-Polysiloxane Hydrogels “, Journal of Applied Polymer Science,Vol. 60,1193-1199 (1996)。 Examples of such silicon-containing polyurethanes are disclosed in numerous publications, including Lai, Yu-Chin, "The Role of Bulky Polysiloxanylalkyl Methacryates in Polyurethane-Polysiloxane Hydrogels", Journal of Applied Polymer Science, Vol. 60,1193-1199 ( 1996). PCT 公开申请号W0 96/31792公开了这样的单体的实例。 PCT Application Publication No. W0 96/31792 discloses examples of such monomers. 其它含硅聚氨酯单体的实例用式VII和VIII表示: Examples of the formula VII and VIII of the silicon-containing urethane monomer is represented:

Figure CN101977638AD00134

[0086]其中: [0086] wherein:

[0087] D表示具有6-30个碳原子的烷基双基、烷基环烷基双基、环烷基双基、芳基双基或烷芳基双基; [0087] D represents an alkyl group having 6-30 carbon atoms diradical, an alkyl cycloalkyl diradical, an alkyl cycloalkyl diradical, an aryl diradical or an alkylaryl diradical group;

[0088] G表示具有1-40个碳原子的烷基双基、环烷基双基、烷基环烷基双基、芳基双基或烷芳基双基,其可以在主链中包含醚、硫或胺键连接; [0088] G denotes an alkyl diradical having 1 to 40 carbon atoms, a cycloalkyl diradical, an alkyl cycloalkyl diradical, an aryl diradical or alkaryl diradical which may contain in the main chain ethers, sulfur or amine linkage;

[0089] *表示氨基甲酸酯或脲基连接;a是至少1 ; [0089] * denotes a urethane or urea groups are connected; a is at least 1;

[0090] A表示式IX的二价聚合基团; [0090] A formula IX represents a divalent polymeric radical;

[0091] 其中E—(cH2)m- [0091] wherein E- (cH2) m-

-Si—O- -Si-O-

Rs Rs

-Si-(CH2)m—E Rs -Si- (CH2) m-E Rs

w w

[0092] 各个民独立地表示具有1-10个碳原子的烷基或氟取代的烷基,其可以在碳原子间含有醚键连接; [0092] China each independently represents an alkyl group having 1 to 10 carbon atoms or a fluorine-substituted alkyl group, which may contain ether linkages between carbon atoms;

[0093] m'为至少1 ;并且 [0093] m 'is at least 1; and

13[0094] 13 [0094]

[0095] [0095]

[0096] [0096]

[0097] [0097]

[0098] [0098]

[0099] [0099]

[0100] [0101] [0102] [0100] [0101] [0102]

[0103] [0103]

[0104] [0104]

[0105] [0105]

[0106] [0107] [0106] [0107]

[0108] [0108]

P是使该部分分子量为400到10,000的数目; The part P is the number molecular weight is 400 to 10,000;

各个E和E'独立地表示式X代表的可聚合不饱和有机基团 Each E and E 'independently represent the formula X represents a polymerizable unsaturated organic radical

Figure CN101977638AD00141

其中: among them:

R6是氢或甲基; R6 is hydrogen or methyl;

R7是氢、具有1-6个碳原子的烷基、或-C0-Y-R9基团,其中Y是-0-、-s-或-NH- R7 is hydrogen, alkyl having 1-6 carbon atoms, or -C0-Y-R9 radical wherein Y is -0 -, - s- or -NH-

R8是具有1-10个碳原子的二价亚烷基; R8 is a divalent alkylene group having 1 to 10 carbon atoms;

R9是具有1-12个碳原子的烷基; R9 is an alkyl group having 1 to 12 carbon atoms;

X 表示-CO-或-0C0-; X represents -CO- or -0C0-;

Z表示-0-或-NH-; Z represents -0- or -NH-;

Ar表示具有6-30个碳原子的芳基; Ar represents an aryl group having 6 to 30 carbon atoms;

w为0-6 ;x是0或1 ;y是0或1 ;z是0或1。 w is 0-6; x is 0 or 1; y is 0 or 1; Z is 0 or 1.

含硅聚氨酯单体的更具体的实例用式(XI)表示: More specifically, the silicon-containing urethane monomer is represented by the formula Examples of (XI):

E' E '

Figure CN101977638AD00142

其中m是至少1,并优选是3或4,a是至少1,并优选是1,p是使其分子量为400-10,000的数目,优选是至少30,R1(l是除去异氰酸酯基团后二异氰酸酯的双基,例如异佛尔酮二异氰酸酯的双基,各个E"是下式表示的基团: [0109] Wherein m is at least 1, and preferably 3 or 4, a is at least 1, and preferably is 1, p is a number so that molecular weight of 400 to 10,000, preferably at least 30, R1 (l by removing the isocyanate groups after diradical of a diisocyanate, such as isophorone diisocyanate, bis ester group, each E "is a group represented by the formula: [0109]

Figure CN101977638AD00143

[0110] 优选的含硅水凝胶材料包括(在共聚的大体积单体混合物中)5-50重量%,优选10-25重量%的一种或多种含硅大分子单体;5-75重量%,优选30-60重量%的一种或多种聚硅氧烷基烷基(甲基)丙烯酸单体;和10-50重量%,优选20-40重量%的亲水性单体。 [0110] Preferred silicon containing hydrogel material comprises (in bulk copolymerized monomer mixture) 5-50% by weight, preferably 10 to 25 wt% of one or more silicon containing macromers; 5- 75 wt%, preferably 30-60 wt% of one or more polysiloxanylalkyl (meth) acrylic monomer; and 10-50 wt%, preferably 20-40 wt% hydrophilic monomer . 通常,所述含硅大分子单体是在分子两端或更多端用不饱和基团封端的聚有机硅氧烷。 Typically, the silicon-containing macromonomer is a more or both molecular ends capped with an unsaturated group terminated polyorganosiloxane. 除上述结构式中的端基外,Deichert等人的美国专利4,153,641公开了其它不饱和基团,包括丙烯氧基或甲基丙烯氧基。 In addition to the end groups of the formulas, Deichert et al U.S. Patent No. 4,153,641 discloses additional unsaturated groups, including propylene group or a methacryloyloxy group. 含延胡索酸酯的材料例如Lai的美国专利5,512,205、 Fumarate-containing material, for example, U.S. Patent No. 5,512,205 to Lai,

145,449,729和5,310,779中教导的那些也是可用于本发明的基底。 145,449,729 and 5,310,779 taught a substrate may be used are those of the present invention. 优选的是,所述硅烷大分子单体是含硅的碳酸乙烯酯或氨基甲酸乙烯酯或具有一个或多个硬-软-硬嵌段和用亲水性单体封端的聚氨酯_聚硅氧烷。 Preferably, the silane macromonomer is a silicon-containing vinyl carbonate or vinyl carbamate or having one or more hard - Soft - Hard block and a hydrophilic monomer terminated polyurethane silicone _ alkyl.

[0111] 适合的亲水性单体形成可用于本发明的水凝胶,例如含硅水凝胶材料。 [0111] Suitable hydrophilic monomers form hydrogels useful in the present invention, for example, a silicon-containing hydrogel materials. 有用的单体的实例包括酰胺,例如二甲基丙烯酰胺、二甲基甲基丙烯酰胺;环内酰胺例如n-乙烯基-2-吡咯烷酮和用可聚合基团功能化的聚亚烷基二醇。 Examples of useful monomers include amides such as dimethyl acrylamide, dimethyl methacrylamide; e.g. n- cyclic lactam and a vinyl-polymerizable functional group of the polyalkylene glycol alcohol. 可用的功能化的聚亚烷基二醇的实例包括含有单甲基丙烯酸酯或双甲基丙烯酸酯端基的不同链长的聚(二乙二醇)。 Available functionalized polyalkylene glycols include polyethylene of different chain lengths containing monomethacrylate or dimethacrylate end groups (diethylene glycol). 在一个优选的实施方案中,所述聚亚烷基二醇聚合物含有至少两个亚烷基二醇单体单元。 In a preferred embodiment, the polyalkylene glycol polymer containing at least two alkylene glycol monomer units. 其它的例子有美国专利5,070, 215中公开的亲水性碳酸乙烯酯或氨基甲酸乙烯酯单体,以及美国专利4,910,277中公开的亲水性噁唑酮单体。 Other examples include U.S. Patent No. 5,070, hydrophilic vinyl carbonate or vinyl carbamate monomers disclosed in the 215, and the hydrophilic oxazolone monomers disclosed in U.S. Patent No. 4,910,277. 其它合适的亲水性单体对于本领域技术人员来说是显而易见的。 Other suitable hydrophilic monomers of ordinary skill in the art will be apparent.

[0112] 形成器件用添加剂和共聚单体 [0112] forming additives and comonomers device

[0113] 所述单体混合物可在需要时和不损害本发明的目的和效果的范围内包括各种添加剂,例如抗氧化剂、着色剂、紫外吸收剂和润滑剂。 [0113] The monomer mixture may be within the range when needed and does not impair the objects and effects of the present invention include various additives, such as antioxidants, colorants, ultraviolet absorbers and lubricants.

[0114] 单体混合物可根据成型的聚合物制品的目的用途等,通过使用一种或至少两种上述共聚单体和低聚物,以及,如果需要,一种或多种交联剂来制备。 [0114] The monomer mixture can be prepared according to the intended use of the molded polymer article and the like, by using one or at least two of the above comonomers and oligomers, and, if desired, one or more crosslinking agents .

[0115] 当成型的聚合物制品为例如医疗产品,尤其是隐形眼镜时,所述单体混合物由一种或多种硅化合物例如硅氧烷基(甲基)丙烯酸酯、硅氧烷基(甲基)丙烯酰胺和含硅低聚物合适的制备,以获得具有高透氧性的隐形眼镜。 [0115] When the molded polymer article, for example, medical products, in particular contact lens, the monomer mixture of one or more silicon compounds such as silicone-based (meth) acrylate, siloxanyl ( methacrylamide and suitable silicon-containing oligomer prepared), to obtain a contact lens having high oxygen permeability.

[0116] 单体混合物可包括其它成分,例如交联剂、内部润湿剂、亲水性单体单元、增韧剂、 以及其它本领域公知的成分。 [0116] The monomer mixture may include other ingredients, such as crosslinking agents, internal wetting agents, hydrophilic monomeric units, toughening agents, and other art-known components.

[0117] 尽管不需要,单体混合物可包括增韧剂,其量优选低于约80重量%,例如约5-约80重量%,更通常为约20-约60重量%。 [0117] Although not required, the monomer mixture may include toughening agents, preferably in an amount less than about 80% by weight, for example from about 5 to about 80 wt%, more typically from about 20 to about 60 wt%. 美国专利4,327,203中描述了合适的增韧剂的实例。 U.S. Patent No. 4,327,203 describes examples of suitable toughening agents. 这些试剂包括环烷基丙烯酸酯或甲基丙烯酸酯,例如丙烯酸甲酯和甲基丙烯酸甲酯、叔丁基环己基甲基丙烯酸酯、异丙基环戊基丙烯酸酯、叔戊基环庚基甲基丙烯酸酯、叔丁基环己基丙烯酸酯、异己基环戊基丙烯酸酯和甲基异戊基环辛基丙烯酸酯。 These agents include cycloalkyl acrylates or methacrylates, such as methyl acrylate and methyl methacrylate, t-butylcyclohexyl methacrylate, isopropyl acrylate, cyclopentyl, tert-amyl cycloheptylmethyl acrylate, t-butyl cyclohexyl methacrylate, isohexyl cyclopentyl acrylate and methyl isoamyl cyclooctyl acrylate. 合适的增韧剂的其它实例描述于美国专利4,355,147中。 Other examples of suitable toughening agents are described in U.S. Patent No. 4,355,147. 该参考文献描述了多环丙烯酸酯或甲基丙烯酸酯, 例如异冰片基丙烯酸酯和甲基丙烯酸酯、二环戊二烯基丙烯酸酯和甲基丙烯酸酯、金刚烷基丙烯酸酯和甲基丙烯酸酯、和异松菔基丙烯酸酯和甲基丙烯酸酯。 This reference describes polycyclic acrylates or methacrylates such as isobornyl acrylate and methacrylate, dicyclopentadienyl acrylate and methacrylate, adamantyl acrylate and methacrylate, esters, pine and iso turnip acrylate and methacrylate. 美国专利5,270,418 中提供了增韧剂的其它实例。 U.S. Patent No. 5,270,418 provides further examples of toughening agents. 该参考文献描述了支链烷基羟基环烷基丙烯酸酯、甲基丙烯酸酯、丙烯酰胺和甲基丙烯酰胺。 This reference describes branched alkyl hydroxyl cycloalkyl acrylates, methacrylates, acrylamide and methacrylamide. 代表性的实例包括4-叔丁基-2-羟基环己基甲基丙烯酸酯(TBE) ;4-叔丁基-2-羟基环戊基甲基丙烯酸酯;甲基丙烯酰氧基氨基-4-叔丁基-2-羟基环己烧;6-异戊基-3-羟基环己基甲基丙烯酸酯;甲基丙烯酰氧基氨基-2-异己基-5-羟基环戊烷。 Representative examples include 4-tert-butyl-2-hydroxycyclohexyl methacrylate (TBE); 4-tert-butyl-2-hydroxycyclopentyl methacrylate; methacryloxy-amino-4 - tert-butyl-2-hydroxy-cyclohexyl burning; 6- isopentyl-3-hydroxycyclohexyl methacrylate; methacryloxy-amino-2-isohexyl-5- hydroxycyclopentane.

[0118] 特别是对于隐形眼镜,对某些用于形成含硅水凝胶的单体进行氟化以减少在其制造的隐形眼镜上积累沉积物,如美国专利4,954,587,5, 079,319,5, 010,141和6,891,010 中所述。 [0118] In particular contact lenses, some of the monomers used for forming the silicon-containing fluorinated hydrogels to reduce the accumulation of deposits on contact lenses made thereof, as described in U.S. Patent No. 4,954,587,5, 079,319,5, 010,141 and 6,891,010 the. 此外,已发现使用具有某些氟化侧链基团,即-(CF2)-H的含硅单体能改善亲水单体单元和含硅单体单元间的相容性,如美国专利5,387,662和5,321,108中所述。 Further, it has been found having certain fluorinated side groups, i.e. - (CF2) -H silicon-containing monomers can improve compatibility between the hydrophilic silicon-containing monomer units and monomer units, as described in U.S. Patent No. 5 , 387,662 and 5,321,108 in the.

[0119] 如上文所述,表面结构和组成决定了固体材料的许多物理性能和最终用途。 [0119] As described above, surface structure and composition determine many of the physical properties of a solid material and end use. 诸如润湿、摩擦、粘附或润滑的性能很大程度上受表面性质的影响。 Such as wetting, friction, adhesion or lubricity performance is largely influenced by the surface properties. 表面性质的改变在生物相容性起关键作用的生物技术应用中具有特别重要的意义。 Changing the surface properties of particular importance in biotechnological applications play a key role in biocompatibility. 因此,需要提供具有光学透明的亲水表面膜的含硅水凝胶隐形眼镜,其不仅具有改善的可润湿性,还允许在人眼中使用更长的时间。 Accordingly, it is necessary to provide silicon containing hydrogel contact lens having a hydrophilic surface film is optically transparent, having not only an improved wettability, but also allows for longer time in the human eye. 在长时间配戴含硅水凝胶镜片的情况下,需要进一步提供具有光学透明表面膜的改善的含硅水凝胶隐形眼镜,其不仅具有改善的脂质和微生物性质,还通常允许在人眼中使用更长的时间。 In the case where the silicon-containing extended-wear hydrogel lenses, the need for further improved silicon-containing hydrogel contact lens with an optically clear surface film, which not only have improved lipid and microbial properties, but also typically allow people the eyes of a longer period of time. 这样的经表面处理的镜片在实际使用中配戴舒适,允许更长时间的配戴, 而不刺激角膜或对角膜产生其它副作用。 Such a surface treated lens is comfortable to wear in actual use, it allows longer wear, without stimulating the cornea or produce other adverse effects on the cornea.

[0120] 人们还期望将这些表面增强的涂层用于可植入的医疗器件例如人工晶状体材料以减少镜片上皮细胞对植入器件的附着,以及减少人工晶状体通过插入器导入眼部时的摩擦。 [0120] It is also desirable to enhance these surface coatings for implantable medical devices such as intraocular lens materials to reduce the attachment of lens epithelial cells in the implant, and to reduce friction when the IOL is introduced into the eye by inserting .

[0121] 本发明可用于对聚合物器件进行表面处理。 [0121] The present invention may be used for surface treatment of the polymer device. 所述表面处理包括通过使相互作用的嵌段共聚物的互补相互作用官能团与聚合物基底表面的相互作用官能团反应,将相互作用嵌段共聚物结合到聚合物医疗器件基底的表面。 The surface treatment comprises the interaction of functional groups reactive functional group interacting with the surface of the polymer substrate, the binding interaction to the surface of a block copolymer polymeric medical device substrate by reacting complementary interactive segmented block copolymers.

[0122] 如前所述,为根据本发明嵌段共聚物进行隐形眼镜的表面改性,将互补官能团整合到隐形眼镜材料(即基底)表面和用作表面改性处理聚合物(表面改性剂)的相互作用的嵌段共聚物的化学结合单元嵌段之间。 [0122] As described above, for the surface modification of contact lenses in accordance with the block copolymers of the invention, the complementary functional groups incorporated into the lens material (i.e., substrate) surface serving as a surface modification treatment polymer (surface modifying block copolymers chemical interaction agent) bond between the unit blocks. 例如,如果表面改性剂具有含硼酸的官能团,则要处理的隐形眼镜材料必须具有将与所述表面改性剂反应的互补官能团残基。 For example, if a surface modifying agent having a functional group containing a boronic acid, the contact lens material will have to be treated with the surface modifying agent to react with a complementary functional residues. 在这种情况下,隐形眼镜材料可包括含羟基的单体,例如甲基丙烯酸2-羟乙酯或甲基丙烯酸甘油酯, 以与表面改性剂硼酸官能团相互作用。 In this case, the contact lens material can include hydroxyl group-containing monomers such as 2-hydroxyethyl methacrylate, glyceryl acrylate or methacrylate, with the surface modifying agent to a functional group capable of interacting boronic acid. 类似的,如果由具有提供硼酸的残基的材料形成隐形眼镜,则可使用含甲基丙烯酸2-羟乙基酯或甲基丙烯酸甘油酯官能团的表面改性剂进行本发明的表面改性。 Similarly, if a contact lens is formed from a material having provided boronic acid residues may be used methacrylic acid-containing surface modifier 2-hydroxyethyl acrylate or glycerol methacrylate functional group for surface modification according to the present invention. 所述互补的化学官能团使隐形眼镜的表面和一种或多种表面改性剂的相互作用基团之间能产生结合。 To produce the complementary binding between chemical functional groups of the contact lens surface interacting group and one or more surface modifiers. 官能团间的这种结合在其之间形成化学相互作用。 This binding between functional groups forms a chemical interaction between them. 例如, 含有具有表面羧酸基团的预聚物的隐形眼镜优选使用含有季铵或其它阳离子官能团的表面改性剂进行表面改性。 For example, a prepolymer having a surface containing carboxylic acid groups of the contact lens is preferably subjected to surface modification using surface modifying agents containing quaternary ammonium or other cationic functional groups. 类似的,具有表面阳离子基团的隐形眼镜优选使用含有羧酸单元、 磺酸单元或其它阴离子官能团单元的表面改性剂进行表面改性。 Similarly, the contact lens surface preferably having a cationic group containing carboxylic acid unit, sulfonic acid units or other surface modifying agents anionic functional group for surface modification means. 含有表面相互作用官能团的隐形眼镜和相互作用的表面改性剂之间的反应在本领域技术人员已知的条件下进行。 The reaction between the surface modifying agent containing the contact lenses and the interaction of functional group-surface interactions at the present conditions known to skilled in the art.

[0123] 在基底材料不含相互作用的基团的情况下,可添加相互作用的基团。 [0123] In the case of the base material does not contain a group of interactions, may be added to group interaction. 例如,通过使用表面活化处理例如氧等离子体、氨-丁二烯-氨(ABA)处理和氢-氨-丁二烯-氨(HABA)处理。 For example, oxygen plasma, for example, by using a surface activation treatment ammonia - butadiene - Ammonia (ABA) treatment and hydrogen - amino - butadiene - Ammonia (the HABA) process. 基底材料的等离子体处理是已知的,描述于Valim等的美国专利6,193,369、 6,213,604 和Grobe, III 的6,550,915。 Plasma processing a substrate material is described in U.S. Patent No. 6,193,369 Valim the like, and 6,213,604 Grobe, III is known 6,550,915.

[0124] 涂覆基底的方法包括将所述基底在含有表面改性剂的溶液中浸涂。 [0124] The method of coating a substrate comprising dipping said substrate in a solution containing the surface modifying agent. 所述含有表面改性剂的溶液可在溶剂中主要含有表面改性剂,或可以含有其它物质例如清洁物质和提取物质。 The solution containing a surface modifier may consist essentially of a surface modifying agent in solvent or may contain other substances, for example, cleaning material and extractable material. 其它方法可包括用表面改性剂喷涂器件。 Other methods may include spray coating the device with a surface modifying agent. 为进行共价结合反应,需要使用合适的催化剂,例如缩合催化剂。 For covalent binding reactions, we need to use suitable catalysts, for example, condensation catalyst. 或者,所述基底和表面改性剂可用高压条件处理。 Alternatively, the substrate and the surface modifying agent available processing pressure conditions. 在某些实施方案中,所述基底和表面改性剂可在包装材料中高压处理,以产生涂覆的基底。 In certain embodiments, the substrate and the surface modifying agent may be autoclaved in the packaging material, to produce a coated substrate. 一旦基底和表面改性剂间发生反应,可基本除去剩余的表面改性剂,向基底包装材料中加入包装溶液。 Once the reaction between the substrate and the surface modifier, can substantially remove the remaining surface modifying agent, was added to the packaging substrate packaging material. 然后按常规进行密封和其它加工步骤。 Sealed and then the conventional further processing steps. 或者,在储存和将基底器件运送到使用者的过程中,所述表面改性剂可保留在基底包装材料中。 Alternatively, during storage and transport the substrate to the user device, the surface modifier may remain in the base packing material.

[0125] 现在描述通常的涂覆方法。 [0125] The coating method will now be described generally. 医疗器件,例如商用S0fLenS59TM隐形眼镜从包装中取出,在纯水中浸泡至少15分钟,然后放入聚合物溶液中。 Medical devices, such as commercial S0fLenS59TM contact lens removed from the package, immersed in pure water for at least 15 minutes, and then placed in the polymer solution. 本领域技术人员应当了解的是,这里公开的溶液的量可在特定的环境下调整以适应医疗器件尺寸的需要。 Those skilled in the art will appreciate that the amount of the solution disclosed herein can be adjusted to suit the needs of a medical device in size under certain circumstances. 标记玻璃瓶,加入约4ml聚合物溶液,将镜片放置在每个瓶内。 Labeled bottles, the polymer solution was added about 4ml, the lens is placed in each vial. 当使用两种聚合物溶液涂覆时,放入玻璃瓶之前立即混合。 When two coating the polymer solution immediately before mixing into the glass bottle. 小瓶用硅酮塞子和波纹铝盖密封,随后置于高压釜中一个30分钟的周期。 Vials with silicone stoppers and aluminum caps sealing bellows, and then placed in an autoclave a period of 30 minutes. 将经处理的镜片冷却至少3小时,随后从小瓶中取出,用去离子水润洗至少3次。 At least 3 hours, followed by cooling the lens was removed from the vial treated, washed with deionized water run at least three times. 随后将润洗的镜片放置在新的含有4ml硼酸盐缓冲盐水(经过细菌粘附实验的样品使用磷酸盐)的小瓶中,高压灭菌一个30分钟的周期。 Then rinsed in new lens is placed in 4ml vials containing borate buffered saline (experimental sample through bacterial adhesion phosphate), one autoclave cycle of 30 minutes.

[0126] 其它类型的隐形眼镜,例如包含其它水凝胶材料的那些可使用上文公开的涂覆聚合物来处理。 [0126] Other types of contact lenses, for example, a coating comprising a polymer other disclosed hydrogel materials are those described above may be used to process. 在一个实施方案中,美国专利5,260,000中公开的包含彻1£1打1(3011 A水凝胶材料的PureVision™隐形眼镜用上述公开的涂覆聚合物进行表面处理。(PureVision™隐形眼镜从Bausch and Lomb, Rochester, New York 获得)。一方面,PureVision™ 隐形眼镜首先用在含有空气和氨的腔中产生等离子体放电进行处理,以增加反应性表面官能团的数量。用于表面处理的溶液包括嵌段DMA-GMA共聚物和聚丙烯酸。 In one embodiment, disclosed in U.S. Patent No. 5,260,000 comprises a penetrating 1 £ 1 hit 1 (3011 A hydrogel contact lens material PureVision ™ surface-treated with a coating polymer as disclosed above. (PureVision ™ contact lenses obtained from Bausch and Lomb, Rochester, New York). in one aspect, PureVision ™ contact lens was first used in the chamber containing air and ammonia is generated in plasma discharge treatment, to increase the number of reactive surface functional groups. a surface was treated DMA-GMA include block copolymers and polyacrylic acid.

[0127] 硅水凝胶隐形眼镜包装在容器中,所述容器包括储纳隐形眼镜和无菌包装溶液的部分。 [0127] silicone hydrogel contact lenses packaged in a container, the container comprises a reservoir portion is satisfied, and sterile packaged contact lens solutions. 容器的实例有常规的隐形眼镜泡罩包装。 Examples of the container are conventional contact lens blister packages. 将装有浸在溶液中的隐形眼镜的容器,例如在容器上方用密封圈进行密封。 Immersed in the solution containing the contact lens container, for example, above the container sealing ring. 例如所述密封盖(lidstock)绕着容器的周围进行密封。 For example the closure (lidstock) around the periphery of the container is sealed.

[0128] 溶液和隐形眼镜灭菌后密封于包装容器中。 [0128] After the solution was sterilized and sealed in a contact lens packaging container. 灭菌技术的实例包括将溶液和隐形眼镜曝于热能量、微波辐射、Y辐射或紫外线辐射。 Examples of sterilization techniques include exposing the lens to a solution of thermal energy, microwave radiation, Y radiation or ultraviolet radiation. 具体的实例包括密封在包装容器中时通过例如高压处理将溶液和隐形眼镜加热到至少100°c,更优选至少120°C的温度。 Specific examples include when the packaging container is sealed by the high-pressure treatment, for example, contact lens solution and heated to at least 100 ° c, more preferably at least the temperature to 120 ° C.

[0129] 包装溶液是包含相互作用的嵌段共聚物的水溶液,所述嵌段共聚物的量基于包装溶液总重量优选为0. 02-5. 0重量%。 [0129] packaging solution is an aqueous solution comprising the block copolymer interaction, the amount of the block copolymer based on total weight of the packaging solution preferably 0. 02-5. 0 wt%. 相互作用的嵌段共聚物的具体量根据基底和共聚物而不同,但一般而言,所述相互作用的嵌段共聚物的量在上述范围内。 Specific interaction in accordance with the amount of block copolymer and copolymers of different substrate, but in general an amount within the above range, the interaction of block copolymers.

[0130] 包装溶液的pH优选为约6. 0-8. 0,更优选为约6. 5-7. 8,最优选为6. 7-7. 7。 [0130] packaging solution preferably has a pH of about 6. 0-8. 0, more preferably about 6. 5-7. 8, most preferably 6. 7-7. 7. 合适的缓冲液包括单乙醇胺、二乙醇胺、三乙醇胺、氨丁三醇(三(羟甲基)氨基甲烷,Tris)、 Bis-Tris、Bis-Tris丙烷、硼酸盐、柠檬酸盐、磷酸盐、碳酸氢盐、氨基酸及其混合物。 Suitable buffers include monoethanolamine, diethanolamine, triethanolamine, tromethamine (tris (hydroxymethyl) aminomethane, Tris), Bis-Tris, Bis-Tris Propane, borate, citrate, phosphate , bicarbonate, amino acids, and mixtures thereof. 具体缓冲剂的例子包括硼酸、硼酸钠、柠檬酸钾、柠檬酸、Bis-Tris, Bis-Tris丙烷和碳酸氢钠。 Examples of specific buffering agents include boric acid, sodium borate, potassium citrate, citric acid, Bis-Tris, Bis-Tris Propane, and sodium bicarbonate. 当存在缓冲液时,其量通常为约0. 05-2. 5重量%,优选为0. 1-1. 5重量%。 When the buffer is present in an amount of about 0.5 is typically 05-2. 5% by weight, preferably 0. 1-1. 5% by weight. 某些相互作用的表面活性嵌段共聚物将用作缓冲液,如果需要,可使用补充的缓冲剂。 Certain surfactants interact with the block copolymer used as buffers, if needed, may be used to add a buffer. 已发现稳定化依赖于pH,如下文实施例中所述。 It has been found dependent stabilized to, pH, as herein described in the embodiment.

[0131] 包装溶液还可包括任选为缓冲剂的形式的张力调节剂,以提供同渗质量摩尔浓度为约200-400m0sm/kg,更优选为约250-350m0sm/kg的等渗或近等渗的溶液。 [0131] packaging solution may also comprise buffering agents optionally in the form of a tension adjusting agent, to provide a retentate with about molality 200-400m0sm / kg, more preferably from about 250-350m0sm / kg isotonic or near- infiltration of the solution. 适合的张力调节剂的实例包括氯化钠和氯化钾、葡萄糖、甘油、氯化钙和氯化镁。 Examples of suitable tonicity adjusting agents include sodium chloride and potassium chloride, dextrose, glycerin, calcium and magnesium chloride. 当存在时,这些试剂的量通常为约0. 01-2. 5重量%,优选为约0. 2-约1. 5重量%。 When present, the amount of these agents is typically about 0.5 01-2. 5% by weight, preferably from about 0. 2 to about 1.5 wt%.

[0132] 任选的是,所述包装溶液可包括抗微生物剂,但优选所述溶液不含这样的试剂。 [0132] Optionally, the packaging solutions may include an antimicrobial agent, it is preferred that the solution is free of such agents.

[0133] 可用于本发明的某些实施方案中的相互作用的嵌段共聚物可根据本领域公知的合成方法以及下面实施例中公开的方法来制备。 [0133] The block copolymers useful in certain embodiments of interaction in the present invention may be prepared according to methods known in the art synthetic methods and embodiments disclosed below. 根据本发明使用一种或多种表面改性剂对隐形眼镜进行表面改性在下面实施例中进一步详细描述。 Using one or more surface modifying agents for surface modification of contact lenses is described in further detail in the following examples according to embodiments of the present invention.

[0134] 实施例 [0134] Example

[0135] 实施例A. MAAPBA/DMAPMA-b-NVP共聚物的合成 Synthesis Example A. MAAPBA / DMAPMA-b-NVP Copolymer [0135] Embodiment

17[0136] 向装有磁力搅拌棒、热电偶、冷凝器和SS鼓泡针的500mL 3颈圆底烧瓶中加入155mg AIBN和1. 93g(0. 0094mol) 3-甲基丙烯酰氨基苯基硼酸(MAAPBA)。 17 [0136] 500mL 3-neck round bottom flask equipped with a magnetic stir bar, thermocouple, condenser and SS sparging needle was added 155 mg of AIBN and 1. 93g (0. 0094mol) 3- methacryl amidophenyl acid (MAAPBA). 随后加入3. 21g(0. 0188mol)N-[3-(二甲氨基)丙基]甲基丙烯酰胺(DMAPMA)和0. 50g(0. 00236mol) 0-乙基黄原酸苄基酯(BX)在50mL甲醇中的溶液。 Followed by addition of 3. 21g (0. 0188mol) N- [3- (dimethylamino) propyl] methacrylamide (DMAPMA) and 0. 50g (0. 00236mol) 0- ethylxanthate benzyl ester ( BX) in a solution of 50mL methanol. 将溶液用氩气鼓气30分钟后加热。 The solution was heated for 30 minutes with argon gas drum. 另外,在一个250mL添加漏斗中,49. 21g(0. 443mol)N-乙烯基吡咯烷酮(NVP)在200mL甲醇中的溶液用氮气鼓气15分钟。 Further, in a 250mL addition funnel, 49. 21g (0. 443mol) N- vinylpyrrolidone (NVP) solution of 200mL of methanol and blow with nitrogen for 15 min. 将添加漏斗转移到反应烧瓶中替换氩气鼓泡针。 The addition funnel was transferred to the reaction flask was replaced with argon bubbling needle. 系统维持在氩气反压力下。 The system is maintained under argon backpressure. 将该烧瓶加热到60°C,在该温度下保持6小时。 The flask was heated to 60 ° C, held at that temperature for 6 hours. 随后向烧瓶中滴加NVP溶液,并在60°C下维持聚合另外66小时。 NVP solution was subsequently added dropwise to the flask, and the polymerization is maintained at 60 ° C for additional 66 hours. 将溶液冷却至室温,滴入到6L搅拌的乙醚中沉淀。 The solution was cooled to room temperature and added dropwise to stirred ether precipitated 6L. 过滤分离沉淀物,在65°C下真空干燥获得38.89g(71%)白色固体。 The precipitate was separated by filtration, and dried in vacuo to obtain 38.89g (71%) as a white solid at 65 ° C. 从200mL甲醇到6L乙醚中的再沉淀获得37. 00g产物。 37. 00g product obtained from 200mL of methanol to re-precipitate 6L ether.

[0137] 产物用质子NMR(DMS0-d6)和GPC表征。 [0137] The product was characterized by GPC and proton NMR (DMS0-d6). 在约7. 2-8. Oppm处观察到MAAPBA的苯基质子的共振。 Observed at Oppm to about 7. 2-8 phenyl resonance of protons MAAPBA. DMAPMA共振不能清楚地与PVP共振区分。 DMAPMA resonances could not be clearly distinguished and PVP resonance. GPC使用PLgel RESIpore柱进行,DMF+1. 0M LiBr作为溶剂,三重检测。 GPC using column PLgel RESIpore, DMF + 1. 0M LiBr as solvent, triple detection. 估算分子量为31,000道尔顿(目标=23,300道尔顿),多分散性为1.09。 Estimated molecular weight of 31,000 daltons (target = 23,300 Daltons), a polydispersity of 1.09.

[0138]实施例 B. MAAPBA/DMAPMA-b-DMA/MPC 共聚物的合成 Synthesis Example B. MAAPBA / DMAPMA-b-DMA / MPC Copolymer [0138] Embodiment

[0139] 向装有磁力搅拌棒、热电偶、冷凝器和SS鼓泡针的500mL 3颈圆底烧瓶中加入148mg AIBN和1. 84g (0. 0090mol) 3-甲基丙烯酰氨基苯基硼酸(MAAPBA)。 500mL 3 neck round bottom flask [0139] equipped with a magnetic stir bar, thermocouple, condenser and SS sparging needle was added 148 mg of AIBN and 1. 84g (0. 0090mol) 3- methyl-acrylamido-phenylboronic acid (MAAPBA). 随后加入3. 06g(0. 0180mol)N-[3-( 二甲氨基)丙基]甲基丙烯酰胺(DMAPMA)和0. 50g(0. 00225mol) 乙基-a-(0-乙基氧蒽基)丙酸酯(EEXP)在50mL甲醇中的溶液。 Followed by addition of 3. 06g (0. 0180mol) N- [3- (dimethylamino) propyl] methacrylamide (DMAPMA) and 0. 50g (0. 00225mol) ethyl -a- (0- ethyloxetane anthryl) in 50mL methanol propionate (EEXP). 将溶液用氩气鼓气25分钟后加热。 The solution was heated for 25 minutes with argon gas drum. 另外,在一个250mL添加漏斗中,37. 72g(0. 380mol) N,N-二甲基丙烯酰胺(DMA) 和12. 48g(0. 0423mol)2-甲基丙烯酰氧乙基磷酰胆碱(MPC)在150mL甲醇中的溶液用氮气鼓气15分钟。 Further, in a 250mL addition funnel, 37. 72g (0. 380mol) N, N- dimethylacrylamide (DMA) and 12. 48g (0. 0423mol) 2- methyl-methacryloyloxyethyl phosphoryl bladder base (MPC) solution of 150mL of methanol and blow with nitrogen for 15 min. 将添加漏斗转移到反应烧瓶中替换氩气鼓泡针。 The addition funnel was transferred to the reaction flask was replaced with argon bubbling needle. 系统维持在氩气反压力下。 The system is maintained under argon backpressure. 将烧瓶加热到60°C,并在该温度下保持7小时。 The flask was heated to 60 ° C, and held at this temperature for 7 hours. 随后向烧瓶中滴加NVP溶液,并在60°C下维持聚合另外48小时。 NVP solution was subsequently added dropwise to the flask, and the polymerization is maintained at 60 ° C for an additional 48 h. 将溶液冷却至室温,滴入到6L搅拌的乙醚中沉淀。 The solution was cooled to room temperature and added dropwise to stirred ether precipitated 6L. 过滤分离沉淀物,在65°C下真空干燥获得49.05g(88% )白色固体。 The precipitate was separated by filtration, and dried in vacuo to obtain 49.05g (88%) as a white solid at 65 ° C.

[0140] 产物用质子NMR(DMS0-d6)和GPC表征。 [0140] The product was characterized by GPC and proton NMR (DMS0-d6). 在约7. 2-8. Oppm处观察到MAAPBA的苯基质子的共振。 Observed at Oppm to about 7. 2-8 phenyl resonance of protons MAAPBA. DMAPMA共振不能清楚地与DMA共振区分。 DMAPMA resonances could not be clearly distinguished and DMA resonances. MPC单元的共振在3. 2ppm(三甲基铵质子)和3. 6-4. lppm(氧原子附近的亚甲基质子)处观察到。 MPC in resonance units 3. 2ppm (trimethylammonium protons) and 3. 6-4. Lppm (an oxygen atom near the methylene protons) observed at. GPC使用PLgel RESIpore 柱进行,DMF+1. 0M LiBr作为溶剂,三重检测。 GPC using column PLgel RESIpore, DMF + 1. 0M LiBr as solvent, triple detection. 聚合物未从柱上洗脱。 No polymer eluted from the column.

[0141] 实施例C.用含硼酸的聚合物涂覆隐形眼镜 [0141] Example C. contact lens coated with a polymer containing boronic acid

[0142] 由Balifilcon A制备的隐形眼镜按照标准生产方法进行浇铸和加工。 [0142] Balifilcon A contact lens prepared from the cast and processed according to standard production methods. Balifilcon A是一种共聚物,其包含3-[三(三甲基硅烷氧基)硅烷基]丙基乙烯基氨基甲酸酯、N-乙烯基-2-吡咯烷酮(NVP)、1,3-双[4-乙烯基氧羰基氧)-1_ 丁基]聚二甲基硅氧烷和N-乙烯基氧羰基丙氨酸。 Balifilcon A is a copolymer comprising 3- [tris (trimethylsiloxy) silyl] propyl vinyl carbamate, N- vinyl-2-pyrrolidone (NVP), 1,3- bis [4-vinyloxy carbonyl oxygen) -1_ butyl] polydimethylsiloxane and N- vinyl-butoxycarbonyl alanine. 所有Balifilcon A镜片在经空气等离子体处理后暴露于涂覆聚合物(“实验”组)或含有300ppm EDTA的标准硼酸盐缓冲盐水溶液(“对照”组)中。 All lenses Balifilcon A after exposure to air plasma for coating polymer ( "experimental" group) or a standard borate-buffered saline solution containing 300ppm EDTA (the "control" group).

[0143] 为了用本发明的聚合物涂覆,将各镜片置于含有本发明的聚合物溶解在含有300ppm EDTA的硼酸盐缓冲盐水(BBS)中的3. 8mL 100或250ppm(w/v)溶液的聚丙烯(PP) 泡罩内。 [0143] For coated with a polymer according to the present invention, each lens was placed containing polymer of the present invention is dissolved in a borate buffered saline (BBS) containing 300ppm EDTA in 3. 8mL 100 or 250ppm (w / v ) solution of polypropylene (PP) blister. 密封泡罩,在121°C下高压灭菌30分钟。 Sealed blister, autoclaving at 121 ° C 30 min.

[0144] 表2显示了多种涂覆样品和对照物的不同表面性质。 [0144] Table 2 shows a variety of different surface properties of the coated samples and controls. 实验样品A用实施例A的聚合物涂覆,实验样品B用实施例B的聚合物涂覆。 A test sample coated with a polymer Example A, test samples coated with a polymer B Example B. 通过XPS测定原子浓度,如下文所述。 Atomic concentration by XPS, as described below. [0145]表2 [0145] TABLE 2

[0146] [0146]

Figure CN101977638AD00191

[0147] X射线光电子能谱(XPS)分析 [0147] X-ray photoelectron spectroscopy (XPS) analysis

[0148] XPS 数据使用Physical Electronics Quantera SXM Scanning ESCAMicroprobe 收集。 [0148] XPS data using the Physical Electronics Quantera SXM Scanning ESCAMicroprobe collected. 该仪器使用单色铝阳极,在18kV和100瓦特的高功率模式和15kV和0. 25瓦特/微米的低功率模式下操作。 The instrument uses a monochromatic Al anode operated at 18kV and a low power mode 100 watts of high-power mode and 15kV and 0.25 watts / m. 所有高功率采集在1400微米XlOO微米分析区进行。 All high power collection XlOO microns 1400 microns in the analysis zone. 使用双束中和(离子和电子)。 Using dual-beam neutralization (ions and electrons). 仪器基础压力是δχΙΟ,ΐοπ·,操作过程中压力小于或等于lxliTtorr。 Instrument base pressure is δχΙΟ, ΐοπ · process, the operating pressure is less than or equal to lxliTtorr. 该仪器使用FAT模式操作的半球分析器。 The mode of operation of the instrument using the FAT hemispherical analyzer. 将gauze透镜与半球分析器偶联以增加信号输出。 The gauze lens coupled with a hemispherical analyzer in order to increase signal output. 假定Cls光电子的非弹性平均自由路程为35A,该仪器以45的取样角取样时实测深度为75人。 Assume inelastic mean free path Cls photoelectron is 35A, when the instrument at the sampling depth is measured angle of 45 to 75 people. XPS中取样深度的方程式是: XPS sampling depth of the equation is:

[0149] θ λ sin3 = d [0149] θ λ sin3 = d

[0150] 其中d是取样深度,λ是光电子非弹性平均自由路程,θ是样品表面和分析器轴之间的夹角。 [0150] where d is the sampling depth, λ is the photoelectron inelastic mean free path, θ is the angle between the sample surface and the axis of the analyzer. 利用低分辨检查谱(O-IlOOeV)分析各样本,以鉴定样本表面的元素。 Analysis of each sample using a low-resolution inspection spectrum (O-IlOOeV), to identify the elements of the sample surface. 通过对光电子峰面积的积分完成元素组成的量化。 By completing the integration of the photoelectron peak areas of elements consisting of quantification. 考虑分析器传输、光电子截面和源角校正以提供精确的原子浓度值。 Consider Analyzer transmission, photoelectron cross-section, and source angle correction to provide accurate atomic concentration values.

[0151 ]实施例D :DMA-b-DMAPMA/MAAPBA/DMA 的合成 [0151] Example D: Synthesis of DMA-b-DMAPMA / MAAPBA / DMA of

[0152] 向装有磁力搅拌棒、添加漏斗和热电偶的500mL 3颈圆底烧瓶中加入0. 033g AIBN(基于RAFT试剂量为20mol % )、0· 354g (0. OOlOmol) 2-(十二烷基二硫酯基)丙酸、 20. Og(0. 202mol)蒸馏的N,N-二甲基丙烯酰胺(DMA)和80mL 二噁烷。 [0152] 500mL 3 neck round bottom flask equipped with a magnetic stirring bar, addition funnel and thermocouple was added 0. 033g AIBN (based RAFT agent in an amount of 20mol%), 0 · 354g (0. OOlOmol) 2- (ten dialkyl disulfide ester group) propionic acid, 20. Og (0. 202mol) distilled N, N- dimethylacrylamide (DMA) and 80mL dioxane. 添加漏斗中加入1.37g(0. 0081mol)去阻聚和蒸馏的N_[3_( 二甲氨基)丙基]甲基丙烯酰胺(DMAPMA)、 0. 83g(0. 0040mol)3-甲基丙烯酰氨基苯基硼酸(MAAPBA)和1. 20g(0. 121mol)蒸馏的N, N-二甲基丙烯酰胺(DMA)在30mL 二噁烷中的溶液。 The addition funnel was added 1.37g (0. 0081mol) to polymerization and distillation N_ [3_ (dimethylamino) propyl] methacrylamide (DMAPMA), 0. 83g (0. 0040mol) 3- methacryloxy aminophenyl boronic acid (MAAPBA) and 1. 20g (0. 121mol) was distilled in N, N- dimethyl acrylamide solution (DMA) in 30mL of dioxane. 两种溶液均单独用氮气鼓泡至少30分钟后加热,随后维持在氮气保护下进行反应。 Both solutions were heated separately at least for 30 minutes with nitrogen sparging, followed by maintaining the reaction under nitrogen. 反应加热至60°C。 The reaction was heated to 60 ° C. 2. 75小时后,将添加漏斗中的溶液加入到反应烧瓶中。 After 2.75 hours, the addition funnel was added to the reaction flask. 总共加热12小时后停止加热,将冷却的溶液滴加到6L机械搅拌的乙醚中。 After a total of 12 hours heating was stopped heating, the cooled solution was added dropwise to a mechanically stirred ethyl ether 6L. 真空过滤分离沉淀物。 The precipitate was isolated by vacuum filtration. 固体在40°C下真空干燥至少18小时,获得22.55g 淡黄色固体。 The solid was dried in vacuo at least 18 hours at 40 ° C, to obtain a light yellow solid 22.55g.

[0153] 为除去RAFT端基,将共聚物溶于含有0. 53g(0. 0032mol)AIBN的IOOmL 2-丙醇中。 [0153] To remove the RAFT end group, comprising the copolymer is dissolved in 0. 53g (0. 0032mol) AIBN in IOOmL 2- propanol. 溶液用氮气鼓泡1小时,随后在氮气覆盖下在80°C下加热12小时。 Solution was bubbled with nitrogen for 1 hour, then heated at 80 ° C for 12 hours under a nitrogen blanket. 将冷却的溶液滴加到6L机械搅拌的乙醚中沉淀。 The cooled solution was added dropwise to stirred ether 6L mechanical precipitated. 真空过滤收集白色固体,并在85°C下真空干燥获得18.75g产物。 As a white solid was collected by vacuum filtration, and dried in vacuo to obtain 18.75g product at 85 ° C.

[0154] *注意:该聚合作用产生嵌段共聚物? [0154] * Note: This polymerization to produce a block copolymer? 0默-嵌段-(0默?默/默4?84/1)默),其中第二嵌段实际上是在添加DMAPMA、MAAPBA和DMA时剩余的还未聚合的DMA的统计共聚。 The remaining not yet polymerized DMA statistical copolymerization (0 silently / Mo 4 84/1??) Mo), wherein the second block is actually added DMAPMA, MAAPBA and DMA - Mo 0 - block. 因此第二“嵌段”是异质组成的。 Thus the second "block" is a heterogeneous composition. 产生统计共聚或异质组成嵌段作为第二嵌段的聚合也被认为是本发明的反应性分段嵌段共聚物。 Generating a statistical copolymerization or compositionally heterogeneous block is also considered as the polymerization of the second block segment of the block copolymer is the reaction of the present invention.

[0155] 用质子NMR(甲醇-d4)、GPC、Karl_Fischer和元素分析表征产物。 [0155] Proton NMR (methanol -d4) GPC, Karl_Fischer and elemental analysis, the product was characterized 在约7. 1-7. 8ppm 处观察到MAAPBA的苯基质子的共振。 Phenyl proton resonances were observed at about MAAPBA of 7. 1-7. 8ppm. DMAPMA共振不能清楚地与DMA共振区分。 DMAPMA resonances could not be clearly distinguished and DMA resonances. GPC在35°C 下,在含0. OlM硝酸锂的DMF中进行。 GPC, in the lithium nitrate containing 0. OlM of DMF at 35 ° C. 柱组由3根来自Polymer Standards Services的8mmX 300mm GRAMLinear M柱组成。 Column group consisting of 3 8mmX 300mm GRAMLinear M columns from Polymer Standards Services composition. 使用Narrow MW PMMA参照标准物进行校准。 Narrow MW PMMA using reference standards for calibration. 主峰分子量为17,900 (目标值=23,200),多分散性为1. 8。 A main peak molecular weight of 17,900 (target = 23,200), a polydispersity of 1.8. 元素分析结果为: Elementary analysis:

[0156]表 3 [0156] TABLE 3

[0157] [0157]

Figure CN101977638AD00201

[0158] *KarI-Fischer分析测定的水含量为1. 7% [0158] * KarI-Fischer analysis measured water content was 1.7%

[0159] 实施例F :用DMA-b-DMAPMA/MAAPBA/DMA聚合物涂覆隐形眼镜 [0159] Example F: with DMA-b-DMAPMA / MAAPBA / DMA polymer coated lenses

[0160] 由Balafilcon A制备的隐形眼镜按照标准生产方法进行浇铸和加工。 [0160] Balafilcon A contact lens prepared from the cast and processed according to standard production methods. 所有Balafilcon A镜片在经空气等离子体处理后暴露于涂覆聚合物(“实验”组)或含有300ppm EDTA的标准硼酸盐缓冲盐水溶液(“对照”组)中。 All Balafilcon A lenses after the coating is exposed to air plasma treated polymer ( "experimental" group) or a standard borate-buffered saline solution containing 300ppm EDTA (the "control" group).

[0161] 为了用本发明聚合物涂覆,将各镜片置于含有本发明聚合物溶解在含有300ppm EDTA的BBS中的3. 8mL 500ppm(w/v)溶液的聚丙烯(PP)泡罩中。 [0161] For the present invention with a polymer coating, each lens was placed (PP) blister containing 3. (w / v) solution 8mL 500ppm polypropylene polymers of the present invention is dissolved in BBS containing 300ppm EDTA in the . 密封镜片泡罩,在121 °C 下高压灭菌30分钟。 Lens blister sealed, autoclaved at 121 ° C 30 min.

[0162]表 4 [0162] TABLE 4

[0163] [0163]

Figure CN101977638AD00202

[0164] 实施例G :GMA-b-DMA共聚物基质的合成,其中各嵌段的分子量不同(证明用CRP 控制分子量)。 [0164] Example G: Synthesis of GMA-b-DMA copolymer matrix, wherein each of the blocks having different molecular weights (molecular weight controlling demonstrated by CRP). [0165] 表5 [0165] TABLE 5

[0166] [0166]

Figure CN101977638AD00211

[0167] *所有反应中加入约33mg AIBN0 [0167] * All reactions were added about 33mg AIBN0

[0168] *注意:所有的反应以类似的方式使用上表中给出的量进行。 [0168] * Note: All reactions in a similar manner using the amounts given in the table were. 下面使用反应2748-114作为上述方法的一个例子进行描述。 2748-114 be described below using the reaction as an example of the above method. 称取350mg (0. 97mmol) SI-十二烷基-S- ( α,α ' - 二甲基-α 〃 -乙酸)三硫代碳酸酯和33mg AIBN置于250ml圆底烧瓶中。 Weigh 350mg (0. 97mmol) SI- dodecyl -S- (α, α '- dimethyl 〃 -α - acetic acid) trithiocarbonate and 33mg AIBN was placed 250ml round bottom flask. 向烧瓶中加入20ml(194mmOl)N,N-二甲基丙烯酰胺(DMA)和60ml 二噁烷,用隔膜密封烧瓶,随后通入氩气去氧30分钟。 Was added 20ml (194mmOl) N To a flask, N- dimethyl acrylamide (DMA) and 60ml of dioxane, the flask was sealed with a septum and then purged with argon dideoxy 30 minutes. 将烧瓶置于油浴(50°C)中6.0小时。 The flask was placed in an oil bath (50 ° C) 6.0 hours. 在另一个容器中, 在2. Oml (14. 66mmol)甲基丙烯酸缩水甘油酯(GMA)中鼓入氩气30分钟,在6. 0小时后加入到烧瓶中。 In a separate container, in 2. Oml (14. 66mmol) of glycidyl methacrylate (GMA) was bubbled with argon for 30 minutes and after 6.0 hours was added to the flask. *注意:就在加入GMA前从烧瓶中取少部分并在乙醚中沉淀。 * NOTE: to take a small portion from the flask before GMA addition and precipitated into diethyl ether. 反应在加入GMA 15小时后终止(总反应时间19. 5小时)。 The reaction was terminated after addition of GMA 15 hours (19.5 hours total reaction time). 将最终产物在乙醚中从反应混合物中沉淀出来。 The final product was precipitated from the reaction mixture in diethyl ether.

[0169] 用质子NMR (⑶Cl3)和GPC表征第一沉淀物以及DMA和GMA的嵌段共聚物。 [0169] Proton NMR (⑶Cl3) characterized by a first precipitate and the block copolymer of DMA and GMA and GPC. GPC显示加入GMA嵌段后洗脱峰向更短时间位移(更高的分子量)。 GPC shows the elution peak to shorter time shift (higher molecular weight) was added after the GMA block. 此外,嵌段共聚物的NMR谱显示甲基丙烯酸缩水甘油酯在3. 7ppm和4. 3ppm处有峰。 Further, the NMR spectrum of the block copolymer of glycidyl methacrylate in the display 3. 7ppm and peaks at 4. 3ppm. 下面显示了这些聚合物使用DMF作为洗脱剂的GPC数据,使用PMMA标准物和PVP标准物校准。 The following shows these polymers using DMF as eluent GPC data using PMMA standards and PVP standards for calibration. 尽管分子量的趋势一致,PMMA 标准物显示分子量与聚DMA的理论预期值更接近。 Although the molecular weight consistent trend, PMMA standards show the expected molecular weight is more close to the theoretical value of the polymerization DMA.

[0170]表 6 [0170] TABLE 6

[0171] PMMA标准物PVP标准物 [0171] PMMA standards standard PVP

[0172] 样品Mw Mn Mw Mn [0172] Sample Mw Mn Mw Mn

[0173] [0173]

Figure CN101977638AD00212

[0174]实施例 H :DMA-b-TMAQPMA 的合成 [0174] Example H: Synthesis of DMA-b-TMAQPMA

[0175]称取 350mg (0. 97mmol) SI-十二烷基-S- ( α,α ' - 二甲基-α 〃 -乙酸)三硫 [0175] Weigh 350mg (0. 97mmol) SI- dodecyl -S- (α, α '- dimethyl 〃 -α - acetic acid) trisulfide

代碳酸酯和35mg AIBN置于250ml圆底烧瓶中。 Generation carbonate and 35mg AIBN was placed 250ml round bottom flask. 向烧瓶中加入IOml (97mmol) N, N- 二甲基 Was added IOml (97mmol) N To a flask, N- dimethyl

丙烯酰胺(DMA)和30ml 二噁烷,用隔膜密封烧瓶,随后通入氩气去氧30分钟。 Acrylamide (DMA) and 30ml of dioxane, the flask was sealed with a septum and then purged with argon dideoxy 30 minutes. 将烧瓶置于油浴(50°C)中6.0小时。 The flask was placed in an oil bath (50 ° C) 6.0 hours. 在另一个容器中,在2. 52g(14.8mm0l)N,N-二甲氨基丙基甲基丙烯酸酯(DMAPMA)中鼓入氩气30分钟,然后在6.0小时后加入到烧瓶中。 In another container, 2. 52g (14.8mm0l) N, N- dimethylaminopropyl methacrylate (DMAPMA) was bubbled argon for 30 minutes and after 6.0 hours then added to the flask. *注意:就在加入DMAPMA之前从烧瓶中取少部分在乙醚中沉淀。 * NOTE: to take a small portion of the precipitate in diethyl ether from the flask prior to addition of DMAPMA. 反应在加入DMAPMA 16小时后终止(总反应时间22小时)。 The reaction was terminated after addition of DMAPMA 16 hours (total reaction time 22 hours). 将最终产物在乙醚中从反应混合物中沉淀出来。 The final product was precipitated from the reaction mixture in diethyl ether.

[0176] 用质子NMR(CDCl3)和GPC表征第一沉淀物以及DMA和DMAPMA的嵌段共聚物。 [0176] Proton NMR (CDCl3) characterized by a first precipitate and the block copolymer of DMA and DMAPMA and GPC. GPC 显示在加入DMAPMA嵌段后洗脱峰向更短的时间位移(更高的分子量)。 GPC shows the elution (higher molecular weight) peak displaced towards a shorter time after the addition of DMAPMA block. (使用PMMA标准物分子量从11,000位移到12,000)。 (Using PMMA standards displaced from 11,000 to 12,000 molecular weight). 此外,在NMR谱中,DMAPMA共振不能清楚地与DMA共振区分,但可在约2. 2ppm处观察到N-甲基共振的影响(峰形的改变)。 Further, in the NMR spectrum, DMAPMA resonances could not be clearly distinguished and DMA resonance, but can affect the observed resonance methyl N- (changing peak shape) at about 2. 2ppm.

[0177] 在第二季铵化步骤中,将2g上述沉淀的干燥聚合物溶于15mL N,N_二甲基甲酰胺中。 [0177] In the quaternary ammonium second step, 2g of the dried polymer precipitated above was dissolved in 15mL N, N_-dimethyl formamide. 向该反应中加入l.OmL碘甲烷(化学计算过量)。 To the reaction was added iodomethane l.OmL (stoichiometric excess). 将反应搅拌过夜,在旋转蒸发器上浓缩,随后溶于甲醇中,并在乙醚中沉淀。 The reaction was stirred overnight, concentrated on a rotary evaporator, then dissolved in methanol and precipitated in diethyl ether. 该反应产生嵌段共聚物DMA-b-TMAQPMA。 The reaction yielded the block copolymer DMA-b-TMAQPMA. *TMAPQMA =三甲氨基四丙基甲基丙烯酸酯 * TMAPQMA = tetrapropyl trimethylammonio methacrylate

[0178] 实施例I :DMA-b_MAA的合成 Synthesis of DMA-b_MAA: I Example [0178] Embodiment

[0179]称取 350mg (0. 97mmol) SI-十二烷基-S- ( α,α ' - 二甲基-α 〃 -乙酸)三硫代碳酸酯和35mg AIBN置于250ml圆底烧瓶中。 [0179] Weigh 350mg (0. 97mmol) SI- dodecyl -S- (α, α '- dimethyl 〃 -α - acetic acid) trithiocarbonate and 35mg AIBN 250ml round bottom flask was placed . 向烧瓶中加入IOml (97mmol) N, N- 二甲基丙烯酰胺(DMA)和30ml 二噁烷,用隔膜密封烧瓶,随后通入氩气去氧30分钟。 Was added to the flask IOml (97mmol) N, N- dimethylacrylamide (DMA) and 30ml of dioxane, the flask was sealed with a septum and then purged with argon dideoxy 30 minutes. 将烧瓶置于油浴(50°C)中6.0小时。 The flask was placed in an oil bath (50 ° C) 6.0 hours. 在另一个容器中,在2. 31g(14.6mm0l)三甲基硅烷基甲基丙烯酸酯(TMS-MA)中鼓入氩气30分钟,然后在6. 0小时后加入烧瓶。 In another container, 2. 31g (14.6mm0l) trimethylsilyl methacrylate (TMS-MA) was bubbled argon for 30 minutes and then added to the flask after 6.0 hours. *注意:就在加入TMS-MA 之前从烧瓶中取少部分在乙醚中沉淀。 * NOTE: to take a small portion of the precipitate in diethyl ether from the flask prior to addition of TMS-MA. 反应在加入TMS-MA 16小时后终止(总反应时间22 小时)。 The reaction was terminated after addition of TMS-MA 16 hours (total reaction time 22 hours). 将最终产物在乙醚中从反应混合物中沉淀出来。 The final product was precipitated from the reaction mixture in diethyl ether.

[0180] 用质子NMR(CDCl3)和GPC表征第一沉淀物以及DMA和TMS-MA的嵌段共聚物。 [0180] Proton NMR (CDCl3) characterized by a first precipitate and the block copolymer of DMA and TMS-MA and GPC. GPC 显示加入TMS-MA嵌段后洗脱峰向更短的时间(更高的分子量)。 After the addition of TMS-MA show GPC elution peak to shorter block time (higher molecular weight). 此外,NMR谱在距三甲基硅烷基单元Oppm处具有质子共振。 Further, NMR spectrum from trimethylsilyl units at Oppm a proton resonance.

[0181] 在第二脱保护步骤中,将3g上述沉淀的干燥聚合物溶于20mL 二噁烷、1. OmL水和1. OmL冰醋酸中。 [0181] In the second deprotecting step, 3g dried polymer precipitated above was dissolved in 20mL dioxane, 1. OmL 1. OmL of water and glacial acetic acid. 将反应在50°C下搅拌2小时,在旋转蒸发器上浓缩,随后在乙醚中沉淀。 The reaction was stirred at 50 ° C 2 hours and concentrated on a rotary evaporator, followed by precipitation in diethyl ether. 该反应产生嵌段共聚物DMA-b-MAA。 The reaction yielded the block copolymer DMA-b-MAA.

[0182] 当本文中显示和描述本发明某些特定的结构和组成时,可在不偏离本发明内容主旨和范围的情况下进行多种改变,这对于本领域技术人员是显而易见的,同样不限于本文所示的具体结构和描述,其范围由所附的权利要求确定。 [0182] As shown and described herein certain specific structure when the composition of the present invention and, various changes may be made without departing from the spirit and scope of the present invention, the content, which the skilled person will be apparent, the same is not limited to the specific configuration shown herein and described, the scope thereof is determined by the appended claims.

Claims (37)

  1. 形成表面改性的医疗器件的方法,所述方法包括:提供在至少一个表面上具有至少一个提供相互作用的官能团的基团的医疗器件;提供包含相互作用的嵌段共聚物的表面改性剂,所述相互作用的嵌段共聚物包括亲水嵌段和具有与所述医疗器件的至少一个提供表面官能团的基团互补的反应性的化学结合单元嵌段;使所述医疗器件的具有相互作用的官能团的至少一个表面与所述表面改性剂接触;以及,使所述器件表面和表面改性剂处于适于在器件表面和表面改性剂之间形成化学相互作用的反应条件下,以形成表面改性的医疗器件,所述化学相互作用选自静电、离子、络合或氢键相互作用。 The method of forming a surface modified medical device, the method comprising: providing a medical device having at least one group of the functional group interaction provided on at least one surface; providing a surface modifying agent comprising a interactive segmented block copolymers of said interaction comprises a block copolymer having a hydrophilic block and at least one of the medical device to provide chemically reactive groups on the surface functional group of complementary binding unit block; the medical device have mutually at least one functional group of the surface in contact with the action surface-modifying agent; and, the device surface and surface modifying agent under the reaction conditions is suitable for forming a chemical interaction between the device surface and surface modifying agent, to form a surface modified medical device, the selected chemical interactions of electrostatic, ionic, complexation or hydrogen bonding interactions.
  2. 2.权利要求1的方法,其中所述医疗器件包括含硅单体。 The method of claim 1, wherein said medical device comprises a silicon-containing monomers.
  3. 3.权利要求2的方法,其中所述含硅单体选自含硅碳酸乙烯酯、含硅氨基甲酸乙烯酯、 具有一个或多个硬-软-硬嵌段并用亲水性单体封端的聚氨酯_聚硅氧烷、含延胡索酸酯的含硅单体、在分子的两端或更多端用不饱和基团封端的聚有机硅氧烷、聚氨酯_聚硅氧烷大分子单体及其混合物。 The method of claim 2, wherein said silicon-containing monomer selected from a silicon-containing vinyl carbonate, vinyl carbamate silicon, having one or more hard - Soft - Hard block and a hydrophilic monomer terminated _ polysiloxane polyurethanes, silicon containing monomers fumarate, or more in both molecular ends capped with an unsaturated group terminated polyorganosiloxane, polyurethane and polysiloxane macromer _ mixture.
  4. 4.权利要求2的方法,其中所述医疗器件包括5-50重量%的一种或多种含硅大分子单体、5-75重量%的一种或多种聚硅氧烷基烷基(甲基)丙烯酸单体、和10-50重量%的亲水性单体作为待共聚的单体混合物。 The method of claim 2, wherein said medical device comprises 5-50% by weight of one or more silicon containing macromers, 5-75 wt% of one or more polysiloxanylalkyl (meth) acrylic monomer, and 10-50% by weight of a hydrophilic monomer as a monomer mixture to be copolymerized.
  5. 5.权利要求2的方法,其中所述医疗器件包括10-25重量%的一种或多种含硅大分子单体、30-60重量%的一种或多种聚硅氧烷基烷基(甲基)丙烯酸单体、和20-40重量%的亲水性单体作为待共聚的单体混合物。 The method of claim 2, wherein said medical device comprises 10-25 weight percent of one or more silicon containing macromers, 30-60% by weight of one or more polysiloxanylalkyl (meth) acrylic monomer, and 20-40% by weight of a hydrophilic monomer as a monomer mixture to be copolymerized.
  6. 6.权利要求1的方法,其中所述医疗器件包括水凝胶材料。 6. The method of claim 1, wherein said medical device comprises a hydrogel material.
  7. 7.权利要求1的方法,其中所述医疗器件包括含硅水凝胶材料。 The method of claim 1, wherein said medical device comprises silicon containing hydrogel materials.
  8. 8.权利要求1的方法,其中所述医疗器件包括与亲水性单体共聚的乙烯基官能化的聚二甲基硅氧烷。 The method of claim 1, wherein said medical device comprising a hydrophilic monomer copolymerizable with the vinyl-functional polydimethylsiloxane.
  9. 9.权利要求1的方法,其中所述医疗器件包括氟化的单体。 9. The method of claim 1, wherein said medical device comprises fluorinated monomers.
  10. 10.权利要求1的方法,其中所述医疗器件包括与亲水性单体共聚的甲基丙烯酸酯官能化的氟化聚环氧乙烷。 10. The method of claim 1, wherein said medical device comprising a hydrophilic monomer copolymerizable with the methacrylate functionalized fluorinated polyethylene oxide.
  11. 11.权利要求1的方法,其中所述医疗器件选自心脏瓣膜、人工晶状体、人工晶状体插入器、隐形眼镜、子宫环、脉管替代物、人工输尿管、血管支架、有晶体眼人工晶状体、无晶体眼人工晶状体、角膜植入物、导管、植入管和人工乳房组织。 11. The method of claim 1, wherein said medical device is selected from heart valves, intraocular lenses, intraocular lens inserters, contact lenses, intrauterine, vessel substitutes, artificial ureters, vascular stents, phakic intraocular lenses, no phakic IOL, corneal implants, catheters, implants, and artificial breast tissue.
  12. 12.权利要求11的方法,其中所形成的医疗器件是软性隐形眼镜。 12. The method of claim 11, wherein the medical device formed is a soft contact lens.
  13. 13.权利要求12的方法,其中所述医疗器件是含硅水凝胶隐形眼镜材料。 13. The method of claim 12, wherein said medical device is a silicon containing hydrogel contact lens material.
  14. 14.权利要求1的方法,其中所述相互作用的嵌段共聚物包括的化学结合单元是选自以下组中的单体:苯乙烯硼酸、3-甲基丙烯酰氨基苯乙烯硼酸、三甲基、2-甲基丙烯酰氧基乙基磺酸盐、3-甲基丙烯酰氨基丙基-N,N, N-三甲基铵盐、2-甲基丙烯酰氧基乙基-N,N, N-三甲基铵盐和含胺单体例如3-甲基丙烯酰氨基丙基-N,N- 二甲胺。 14. The method of claim 1, wherein said block copolymer comprises the interaction of the chemical binding unit selected from the group of monomers: styrene boronic acid, 3-acrylamido-styrene boronic acid, trimethyl group, 2-methacryloyloxyethyl sulfonate, acrylamido-3-propyl -N, N, N- trimethylammonium salt, 2-methacryloyloxyethyl -N , N, N- trimethyl ammonium salts and amine containing monomers such as acrylamido-3-propyl -N, N- dimethylamine.
  15. 15.权利要求1的方法,其中所述相互作用的嵌段共聚物包括选自以下组中的亲水性单元单体:甲基丙烯酸2-羟乙基酯、甲基丙烯酸甘油酯、甲基丙烯酸、丙烯酸、甲基丙烯酰胺、丙烯酰胺、N,N' -二甲基甲基丙烯酰胺、N,N' -二甲基丙烯酰胺、烯键式不饱和的聚环氧烷烃、环内酰胺、N-乙烯基-2-吡咯烷酮、亲水性碳酸乙烯酯、亲水性氨基甲酸乙烯酯单体、2-羟乙基丙烯酸酯、2-(2_乙氧基乙氧基)乙基(甲基)丙烯酸酯、甘油基(甲基) 丙烯酸酯、聚(乙二醇(甲基)丙烯酸酯)、四氢呋喃(甲基)丙烯酸酯、N-乙烯基乙酰胺、 其共聚物、衍生物及组合。 15. The method of claim 1, wherein said interaction comprises a hydrophilic block copolymer unit monomer is selected from the group: 2-hydroxyethyl acrylate methacrylate, glycerol methacrylate, methyl acrylic acid, acrylic acid, methacrylamide, acrylamide, N, N '- dimethyl methacrylamide, N, N' - dimethyl acrylamide, ethylenically unsaturated polyalkylene oxide, a cyclic lactam , N- vinyl-2-pyrrolidone, hydrophilic vinyl carbonate, hydrophilic vinyl carbamate monomers, 2-hydroxyethyl acrylate, 2- (2_ ethoxyethoxy) ethyl ( meth) acrylate, glycidyl (meth) acrylate, poly (ethylene glycol (meth) acrylate), tetrahydrofuran (meth) acrylate, N- vinyl acetamide, copolymers, derivatives and combination.
  16. 16.权利要求1的方法,其中所述相互作用的嵌段共聚物具有下列通式(I): Rl-[(A)m]p-[(B)n]qX (I)其中R1是能够用作原子转移自由基聚合引发剂的部分的反应性残基,A是化学结合单元嵌段,B是亲水单元嵌段,m是1-10,000,n是1_10,000, p和q是自然数,以及X是原子转移自由基聚合引发剂的卤素封端基团或衍生的反应产物。 16. The method of claim 1, wherein said block copolymer has interaction following general formula (I): Rl - [(A) m] p - [(B) n] qX (I) wherein R1 is capable of as atom transfer radical polymerization residue of an initiator moiety, a is a chemical binding unit block, B is a hydrophilic unit block, m is 1-10,000, n is 1_10,000, p and q is a natural number, and X is an atom transfer radical polymerization initiator is a reaction product of a halogen capping group or derivatized.
  17. 17.权利要求1的方法,其中所述相互作用的嵌段共聚物具有下列通式(II): Rl-[(A)m]p-[(B)n]q-R2 (II)其中R1是RAFT试剂或自由基引发剂的形成自由基的残基,A是化学结合单元嵌段,B 是亲水单元嵌段,m是1-10,000,n是1_10,000, p和q是自然数,以及R2是链转移试剂的硫代羰基嵌段或衍生的反应产物。 17. The method of claim 1, wherein said block copolymer has interaction following general formula (II): Rl - [(A) m] p - [(B) n] q-R2 (II) wherein R1 RAFT agent or free radical initiator is a radical forming agent residue, a is a chemical binding unit block, B is a hydrophilic unit block, m is 1-10,000, n is 1_10,000, p and q are natural numbers, and R2 is a block thiocarbonyl or reaction product chain transfer agent derived.
  18. 18.权利要求1的方法,其中所述相互作用的嵌段共聚物具有下列通式(III): Rl-[ (B)n] q-[ (A)m]P-R2-[ (A) Jp-[ (B) J q-Rl (III)其中Rl是RAFT试剂或自由基引发剂的形成自由基的残基,A是化学结合单元嵌段,B 是亲水单元嵌段,m是1-10,000, n是1_10,000, p和q是自然数,R2是二硫酯基团。 Rl- [(B) n] q- [(A) m] P-R2- [(A): 18. The method of claim 1, wherein the block copolymer has the following interaction formula (III) jp- [(B) J q-Rl (III) wherein Rl is a RAFT agent or free radical initiator radical forming agent residue, a is a chemical binding unit block, B is a hydrophilic unit block, m is 1 -10,000, n is 1_10,000, p and q are natural numbers, R2 is a thio ester group.
  19. 19.权利要求1的方法,其中所述相互作用的嵌段共聚物具有1到约1000个化学结合单元。 19. The method of claim 1, wherein said block copolymer has an interaction to about 1,000 chemically combined units.
  20. 20.权利要求1的方法,其中所述相互作用的嵌段共聚物具有1到约100个化学结合单兀。 20. The method of claim 1, wherein said block copolymer has an interaction to about 100 chemically bound single Wu.
  21. 21.权利要求1的方法,其中所述相互作用的嵌段共聚物具有1到约30个化学结合单兀。 21. The method of claim 1, wherein said block copolymer has an interaction to about 30 chemically combined single Wu.
  22. 22.权利要求1的方法,其中所述相互作用的嵌段共聚物具有包含1到约10,000个单元的亲水性嵌段。 22. The method of claim 1, wherein said block copolymer having a hydrophilic interaction block comprising 1 to about 10,000 units.
  23. 23.权利要求1的方法,其中所述相互作用的嵌段共聚物具有包含约10到约1,000个单元的亲水性嵌段。 23. The method of claim 1, wherein said block copolymer having a hydrophilic interaction block comprises from about 10 to about 1,000 units.
  24. 24.权利要求1的方法,其中所述相互作用的嵌段共聚物具有包含约20到约300个单元的亲水性嵌段。 24. The method of claim 1, wherein said block copolymer having a hydrophilic interaction block comprises from about 20 to about 300 units.
  25. 25.表面改性的医疗器件,包括:在至少一个表面上具有至少一个提供反应性官能团的基团的医疗器件;以及用于所述医疗器件的表面的包含化学结合单元嵌段和亲水嵌段的相互作用的嵌段共聚物;其中所述医疗器件的表面与表面改性剂之间发生化学相互作用以形成表面改性的医疗器件,所述化学相互作用选自静电、离子、络合或氢键相互作用。 25. The surface modified medical device, comprising: providing a medical device having at least one group reactive functional group on at least one surface; and a surface comprising a chemical binding of the medical device unit block and a hydrophilic insert interaction of the block copolymer segments; wherein the chemical interaction between the surface modifier and the surface of the medical device to form a surface modified medical device, the selected chemical interaction of electrostatic, ionic, complexation or hydrogen bonding interactions.
  26. 26.权利要求25的表面改性的医疗器件,其中所述医疗器件选自心脏瓣膜、人工晶状体、人工晶状体插入器、隐形眼镜、子宫环、脉管替代物、人工输尿管、血管支架、有晶体眼人工晶状体、无晶体眼人工晶状体、角膜植入物、导管、植入管和人工乳房组织。 Surface modified medical device 25 as claimed in claim 26, wherein said medical device is selected from heart valves, intraocular lenses, intraocular lens inserters, contact lenses, intrauterine, vessel substitutes, artificial ureters, vascular stents, phakic intraocular lenses, aphakic intraocular lenses, corneal implants, catheters, implants, and artificial breast tissue.
  27. 27.权利要求26的表面改性的医疗器件,其中所述医疗器件是亲水性隐形眼镜。 Surface modified medical device of claim 26, wherein said medical device is a hydrophilic contact lens.
  28. 28.权利要求26的表面改性的医疗器件,其中所述医疗器件是水凝胶隐形眼镜。 Surface modified medical device of claim 26, wherein said medical device is a hydrogel contact lens.
  29. 29.权利要求1的方法,其中所述使器件表面和表面改性剂处于适于在器件表面和表面改性剂之间形成共价键的条件下以形成表面改性的医疗器件的步骤在高压条件下进行。 Step 29. The method of claim 1, wherein the device surface and the surface modifying agent is a medical device suitable for forming a covalent bond under conditions to form a modified surface between the device surface and surface modifying agent in carried out under high pressure conditions.
  30. 30.权利要求29的方法,其还包括在高压处理的步骤之前对装有器件和表面改性剂的包装加上密封盖的步骤。 30. The method of claim 29, further comprising the step prior to the step of packaging with high pressure treatment device and the surface modifier plus closure.
  31. 31.权利要求29的方法,其还包括在高压处理后除去表面改性剂,润洗涂覆的器件,提供储存溶液并进一步高压处理所述器件以进行灭菌的步骤。 31. The method of claim 29, further comprising removing a surface modifier after the high pressure treatment, rinse the coated device, providing a solution storage and further processing of the device for high-pressure sterilization step.
  32. 32.权利要求16的方法,其中一个化学结合单元嵌段或亲水性嵌段是统计共聚或异质组成的嵌段。 32. The method of claim 16, wherein a chemical binding unit block or the hydrophilic block is a statistical copolymerization or compositionally heterogeneous block.
  33. 33.权利要求17的方法,其中一个化学结合单元嵌段或亲水性嵌段是统计共聚或异质组成的嵌段。 33. The method of claim 17, wherein a chemical binding unit block or the hydrophilic block is a statistical copolymerization or compositionally heterogeneous block.
  34. 34.权利要求18的方法,其中一个化学结合单元嵌段或亲水性嵌段是统计共聚或异质组成的嵌段。 34. The method of claim 18, wherein a chemical binding unit block or the hydrophilic block is a statistical copolymerization or compositionally heterogeneous block.
  35. 35.权利要求16的方法,其中所述相互作用的嵌段共聚物还包括至少一个选自非结合嵌段、非亲水嵌段及其组合的嵌段。 35. The method of claim 16, wherein the interacting further includes at least one block copolymer selected from the group of nonbinding blocks, nonhydrophilic blocks and combinations thereof block.
  36. 36.权利要求17的方法,其中所述相互作用的嵌段共聚物还包括至少一个选自非结合嵌段、非亲水嵌段及其组合的嵌段。 36. The method of claim 17, wherein the interacting further includes at least one block copolymer selected from the group of nonbinding blocks, nonhydrophilic blocks and combinations thereof block.
  37. 37.权利要求18的方法,其中所述相互作用的嵌段共聚物还包括至少一个选自非结合嵌段、非亲水嵌段及其组合的嵌段。 37. The method of claim 18, wherein the interacting further includes at least one block copolymer selected from the group of nonbinding blocks, nonhydrophilic blocks and combinations thereof block.
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