CN101119754B - 舒适的眼用器件及其制造方法 - Google Patents

舒适的眼用器件及其制造方法 Download PDF

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CN101119754B
CN101119754B CN200680004880.3A CN200680004880A CN101119754B CN 101119754 B CN101119754 B CN 101119754B CN 200680004880 A CN200680004880 A CN 200680004880A CN 101119754 B CN101119754 B CN 101119754B
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polyvinylpyrrolidone
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K·P·麦卡布
R·B·斯蒂芬
H·阿圭拉
W·A·马丁
S·W·尼德尔
A·W·迈尔斯
D·古尔德
K·L·卡纳文
G·A·希尔
D·G·范德拉恩
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Abstract

本发明涉及舒适的眼用器件及生产这种器件的方法。

Description

舒适的眼用器件及其制造方法
相关申请
本申请是2005年2月14日递交的序列号为No.60/652809以及2005年6月30日递交的序列号为No.60/695783的两个美国临时申请的非临时性申请。
发明领域
本发明涉及舒适的眼用器件及生产这种器件的方法。
背景技术
自1950年代起接触镜在商业上使用以提高视力。首批接触镜是由硬质材料制成的。尽管这些眼用透镜目前仍在使用，但由于其初始舒适度不佳而并不适于所有的患者。后来该领域开发出了基于水凝胶的软性接触镜，在当前它们极其流行。这些眼用透镜具有较高的透氧性，因而通常比由硬质材料制成的接触镜配戴更舒适。然而，这些新的透镜并非没有问题。
许多使用者在连续使用八小时到数天时接触镜可能会被磨破，但不会出现任何不良的反应如红眼、发炎、分泌粘液、以及与眼睛干燥有关的接触镜症状。然而，一些使用者在使用了仅几小时后就发生了这些症状。这些接触镜使用者中的许多人利用润滑液来减轻与这些不良反应相关的不适感并取得了一些成功。然而使用这些溶液需要使用者携带额外的溶液，这很不方便。对这些使用者来说，一种更加舒适并且无需使用润滑液的的接触镜将很有用处。因此需要这种接触镜和制造这种接触镜的方法。本发明正是满足了这种需要。
附图简要说明
图1：经过处理的透镜与对照品相比在直径上的变化曲线图。
发明详细说明
本发明包括一种制造眼用透镜的方法，包括、主要由或者由以下步骤组成：倘若所述眼用透镜的配方在其聚合之前不包括润湿剂的话，则用所述润湿剂处理所述聚合化的眼用透镜。
这里使用的“眼用透镜”是指一种放在眼睛内或眼睛上的器件。这种器件可提供光学校正或者可以是化妆用品。眼用透镜包括但不限于软性接触镜、人工晶状体、叠加眼用透镜(overlay lense)、眼睛内嵌物以及光学内嵌物。本发明优选的透镜是由硅酮弹性体或水凝胶制成的软性接触镜，其包括但不限于硅酮水凝胶类和氟水凝胶类。软性接触镜配方披露于US 5710302、WO 9421698、EP406161、JP 2000016905、US 5998498、US 6087415、US 5760100、US 5776999、US 5789461、US 5849811、以及US 5965631中。因而引入上述参考文献的全文作为参考。本发明特别优选的眼用透镜有(已知的美国批准名称)，acofilcon A，alofilcon A，alphafilcon A，amifilcon A，astifilcon A，atalafilcon A，balafilcon A，bisfilcon A，bufilcon A，comfilcon，crofilcon A，cyclofilcon A，darfilcon A，deltafilcon A，deltafilcon B，dimefilconA，drooxifilcon A，epsifilcon A，esterifilcon A，etafilcon A，focofilconA，genfilcon A，govafilcon A，hefilcon A，hefilcon B，hefilcon D，hilafilcon A，hilafilcon B，hioxifilcon B，hioxifilcon C，hixoifilconA，hydrofilcon A，lenefilcon A，licryfilcon A，licryfilcon B，lidofilconA，lidofilcon B，lotrafilcon A，lotrafilcon B，mafilcon A，mesifilconA，methafilcon B，mipafilcon A，nelfilcon A，netrafilcon A，ocufilconA，ocufilcon B，ocufilcon C，ocufilcon D，ocufilcon E，ofilcon A，omafilcon A，oxyfilcon A，pentafilcon A，perfilcon A，pevafilcon A，phemfilcon A，polymacon，silafilcon A，siloxyfilcon A，tefilcon A，tetrafilcon A，trifilcon A，以及xylofilcon A。本发明更优选的眼用透镜是genfilcon A，lenefilcon A，comfilcon，lotrafilcon A，lotrafilcon B，以及balafilcon A。最优选的透镜包括etafilcon A，nelfilcon A，hilafilcon，以及polymacon。
术语“配方”是指用于制备眼用透镜的成分的未聚合混合物。这些成分包括但不限于单体、预聚合物、稀释液、催化剂、引发剂、染料、UV阻断剂、抗菌剂、聚合抑制剂等等。这些配方可以通过记载于前述参考文献以及眼用透镜领域的其它参考文献中的热、化学以及光引发固化技术来进行聚合。这里所使用的术语“聚合的”或“聚合化”是指这些方法。优选的聚合化方法是美国专利No.6822016中公开的光引发技术，因而引入其全文作为参考。
这里使用的术语“处理”是指使所述润湿剂和眼用透镜相接触的物理方法。这些方法不包括将一滴含有润湿剂的溶液滴到眼用透镜佩戴者的眼中或者在透镜嵌入使用者眼内之前将一滴这种溶液滴到眼用透镜上。优选的处理是指在所述眼用透镜出售或以其它方式交给患者之前使所述润湿剂与眼用透镜相接触的物理方法。所述眼用透镜可以在聚合化之后的任何时间用润湿剂进行处理。优选在大于大约50℃的温度下用润湿剂处理所述聚合的眼用透镜。例如，在一些制造隐性眼镜的方法中，将未聚合或部分聚合的制剂置于两个半模之间，进行滚塑或静态浇注并聚合。参见美国专利No.4495313；4680336；4889664；3408429；3660545；4113224和4197266，引入上述所有文献的全文作为参考。在水凝胶的情况下，眼用透镜配方是经过数个不同加工步骤的硬质圆片，所述步骤包括用液体(例如水、无机盐或有机溶液)处理聚合的眼用透镜，以便在其最后的包装之前溶胀或以其它方式平衡该聚合的眼用透镜。未经溶胀或以其它方式平衡的聚合眼用透镜被称为未水合聚合眼用透镜。本发明希望，用润湿剂“处理”所述眼用透镜是在等于或低于室温时向这种“溶胀或平衡”步骤的任何液体中添加润湿剂。此外，在溶胀或平衡步骤过程中所述聚合的非水合眼用透镜与润湿剂可以加热到室温以上。优选的温度范围是从大约50℃加热大约15分钟到以下所述的大致灭菌条件，更优选从大约50℃到大约85℃加热大约5分钟。
而另一种处理方法是使聚合的眼用透镜(水合或者未水合的)与润湿剂在大约室温到大约85℃之间物理接触大约1分钟到大约72小时，优选大约24到大约72小时，之后在大约85℃到150℃之间使所述聚合的眼用透镜与润湿剂物理接触大约15分钟到大约一小时。
在眼用透镜分发给使用者之前，许多眼用透镜包装在单个的泡罩包装中并密封。如这里所使用，这些聚合的眼用透镜称为“水合聚合眼用透镜”。泡罩包装和灭菌技术的实例披露于以下参考文献中，因而引入其全文作为参考：美国专利No.D435966S；4691820；5467868；5704468；5823327；6050398；5696686；6018931；5577367和5488815。这部分制造过程提供了另一种用润湿剂处理眼用透镜的方法，即在密封包装之前向包装溶液中添加润湿剂，然后再灭菌所述包装。这是用润湿剂处理眼用透镜的优选方法。
灭菌可以在任何不同的温度和时段下进行。优选的灭菌条件从大约100℃灭菌大约8小时到大约150℃灭菌大约0.5分钟。更优选的灭菌条件从大约115℃灭菌大约2.5小时到大约130℃灭菌大约5.0分钟。最优选的灭菌条件是大约124℃灭菌大约30分钟。
用于本发明的方法中的“包装溶液”可以是基于水的溶液。典型的包装溶液包括但不限于盐溶液、其它缓冲液、以及去离子水。优选的水性溶液是去离子水或含盐的盐溶液，所述盐包括但不限于氯化钠、硼酸钠、磷酸钠、磷酸氢二钠、磷酸二氢钠或其相应的钾盐。这些成分通常组合形成含有酸及其共轭碱的缓冲液，从而加入酸和碱只会引起相对较小的pH变化。缓冲液还可以包含2-(N-吗啉)乙磺酸(MES)、氢氧化钠、2，2-二(羟甲基)-2，2’，2”-次氮基三乙醇、正三(羟甲基)甲基-2-氨基乙磺酸、柠檬酸、柠檬酸钠、碳酸钠、碳酸氢钠、乙酸、乙酸钠、乙二胺四乙酸等等以及其组合。优选地，所述包装溶液是硼酸盐缓冲的或者磷酸盐缓冲的盐溶液或去离子水。特别优选的包装溶液含有大约1850ppm到大约18500ppm的硼酸钠，最为优选的是大约3700ppm的硼酸钠。
这里使用的术语“润湿剂”是指数量平均分子量为大约至少500的聚合物，当其加入接触镜佩戴者的眼中时能够提供润湿感。优选的润湿剂包括但不限于聚(甲基)丙烯酰胺类[即聚N，N-二甲基丙烯酰胺、聚(N-甲基丙烯酰胺)聚(丙烯酰胺)、聚(N-2-羟乙基甲基丙烯酰胺)、以及聚(葡糖胺丙烯酰胺)]，聚(衣康酸)，透明质酸，黄原胶，阿拉伯树胶(阿拉伯胶)，淀粉，羟烷基(甲基)丙烯酸酯类聚合物[即聚(2-羟乙基甲基丙烯酸酯)、聚(2，3-二羟丙基甲基丙烯酸酯)、以及聚(2-羟乙基丙烯酸酯)]，以及聚乙烯吡咯烷酮。
其它优选的润湿剂包括但不限于上述优选润湿剂的共聚物和接枝共聚物，这种共聚物和接枝共聚物包括亲水性或疏水性单体的重复单元，优选用量在大约小于10wt％，更优选小于大约2wt％。这种亲水性或疏水性单体的重复单元包括但不限于烯烃类，苯乙烯类，环N-乙烯醯胺类，丙烯酰胺类，羟烷基(甲基)丙烯酸酯，烷基(甲基)丙烯酸酯，硅氧烷取代的丙烯酸酯，以及硅氧烷取代的甲基丙烯酸酯。可用于形成上述共聚物和接枝共聚物的亲水性或疏水性单体的特别实例包括但不限于乙烯，苯乙烯，N-乙烯吡咯烷酮，N，N-二甲基丙烯酰胺，2-羟乙基甲基丙烯酸酯，2-羟乙基甲基丙烯酸酯，甲基甲基丙烯酸酯，以及丁基甲基丙烯酸酯，甲基丙烯基氧丙基三甲硅氧基硅烷等等。亲水性或疏水性单体的优选重复单元是N-乙烯吡咯烷酮，N，N-二甲基丙烯酰胺，2-羟乙基甲基丙烯酸酯，甲基甲基丙烯酸酯以及其混合物。润湿剂的其它实例包括但不限于具有碳骨架和聚乙二醇支链的聚合物[即单甲基丙烯酸聚乙二醇酯共聚物]，乙二醇共聚物[1，2-丙二醇、1，3-丙二醇、甲基乙二醇、和四甲基乙二醇的共聚物]。优选的润湿剂是聚乙烯吡咯烷酮，接枝共聚物和聚乙烯吡咯烷酮共聚物，聚乙烯吡咯烷酮(“PVP”)是N-乙烯吡咯烷酮的的聚合产物。PVP以各种分子量存在，从大约500到大约6000000道尔顿。基于Encyclopedia of Polymer Science andEngineering，John Wiley & Sons Inc中记载的运动粘度测量法，这些分子量可表示成K值，并在本申请全文中以这些数值表示。本发明希望使用具有大约K-30到大约K-120的K值的PVP。更优选的K值是大约K-60到大约K-100，最优选是大约K-80到大约K-100。对于etafilcon A眼用透镜的处理来说，PVP的特别优选K值是大约K-80到大约K-95，更优选大约K-85到大约K-95，最优选大约K-90。
润湿剂可以以各种不同的浓度加入包装溶液中，例如大约100ppm到大约150000ppm。例如，如果将润湿剂加入含有未水合聚合眼用透镜的包装溶液中，则所述润湿剂优选以大约30000ppm到大约150000ppm的浓度存在。如果将润湿剂加入含有水合聚合眼用透镜的包装溶液中，则所述润湿剂优选以大约100ppm到大约3000ppm的浓度存在，更优选大约200ppm到大约1000ppm，最优选小于大约500ppm。例如，当本发明中使用etafilcon A透镜并且润湿剂是K-90PVP时，则PVP K-90的优选包装溶液浓度为大约250ppm到大约2500ppm，更优选大约300到大约500ppm，最优选大约350到大约440ppm。
当将etafilcon A接触镜与K-90PVP以大约400到大约500ppm的浓度一起在大于大约120℃的温度下加热大约30分钟时，则该处理后的透镜对于使用者来说比未经处理的透镜更加舒适。此外，这种特殊分子量和浓度的PVP在周期处理过程中不会使所述透镜的直径发生变形或改变或者扭曲使用者的视野。尽管不希望受到加入的任何特定机制的限制，但已知在用K-90PVP处理之后眼用透镜基质中含有K-90PVP。在etafilcon A接触镜中，加入的K-90PVP的优选量为大约0.01mg到大约1.0mg，更优选大约0.10mg到大约0.30mg，最优选大约0.10mg到大约0.20mg。使用者佩戴以这种方式处理后的透镜长达12小时仍然会保持其含有的PVP。
另外，本发明包括一种眼用器件，其包括、主要由或者由聚合的眼用透镜组成，其中倘若所述眼用透镜的配方在其聚合之前不包括润湿剂的话，则用所述润湿剂处理所述聚合的眼用透镜。术语“眼用透镜”、“润湿剂”、“聚合的”以及“配方”均具有上面述及的含义和优选范围。术语“处理后的”与术语处理的具有相同的含义和优选范围。
本发明另外还包括一种利用润湿剂处理聚合的眼用透镜所制备而成的眼用器件，倘若所述眼用透镜的配方在其聚合之前不包括所述润湿剂的话。术语“眼用透镜”、“润湿剂”、“聚合的”以及“配方”均具有上面述及的含义和优选范围。
利用以下实施例进一步详细说明本发明的应用。这些实施例并不意味着限制本发明，仅用于说明其应用。考虑上述说明和以下的实施例，其它的改良方式被认为在本发明的范围之内并且对本领域技术人员来说是显而易见的。
实施例
实施例1
将固化etafilcon A接触镜(Johnson & Johnson Vision Care，inc.出售的1-Day
Figure S06804880320070816D000061
牌接触镜)在去离子水中平衡，并包装于含有硼酸盐缓冲的PVP盐溶液的溶液中(1000mL，氯化钠3.55g，硼酸钠1.85g，硼酸9.26g，以及乙二胺四乙酸0.1g：在24小时内清洗5次，950±μL)，用铝箔盖料密封并灭菌(121℃，30分钟)。在添加PVP之前，各溶液中含有水1000mL，氯化钠3.55g，硼酸钠1.85g，硼酸9.26g，以及乙二胺四乙酸0.1g。使用如下表1中所示的各种不同重量和浓度的PVP。
各透镜中含入的PVP量通过从包装溶液中取出所述透镜并将其用N，N-二甲基甲醯胺(DMF)和去离子水1：1的混合物提取来测定。提取物通过高效液相色谱法(HPLC)算出。每次计算使用三种眼用透镜。结果及其标准偏差列于表1中。
表1
 
样品# PVP类型 浓度(ppm) 眼用透镜中的PVP mg
对照 无 无 无
1 K-12 3000 0.24(0.01)
2 K-12 20000 1.02(0.01)
3 K-30 1500 1.39(0.05)
4 K-30 2000 1.50(0.01)
5 K-60 1000 0.56(0.00)
6 K-60 1500 0.85(0.02)
7 K-60 2500 1.02(0.03)
8 K-90 250 0.10(0.00)
9 K-90 500 0.14(0.00)
10 K-90 1000 0.2(0.01)
11 K-90 2500 0.25(0.02)
12 K-120 500 0.07(0.00)
实施例2
通过实施例1中浓度为0.30％、1.65％和3.00％的K-12、K-30、K-60、K90和K-120PVP的处理和灭菌方法来制备处理后的etafilcon A透镜样品。灭菌之后，将透镜的直径与未经处理的透镜相比较并计算确定是否所述方法改变了其直径。结果，即图1表示了直径变化与特定浓度下PVP类型之间的关系。该数据表明K-12、K90和K-120在透镜直径上具有最小效应。
实施例3
根据实施例1的方法将数个etafilcon A透镜用浓度在500ppm的K-90PVP处理并灭菌。将所述透镜在室温下存放于其包装中大约28天，然后测量直径、基弧、球面倍率和中心厚度。之后将透镜在55℃下加热一个月。测量计算与未经处理处理眼用透镜相比所述透镜的直径、基弧、球面倍率和中心厚度，数据列于表2中。该数据表示用K-90PVP处理的透镜参数在高温下没有受到时间的显著影响。
表2
 
基线 55℃下存放一个月后样品基线的变化
直径(mm) 14.37(0.02) 0.02
基弧(mm) 8.90(0.03) -0.01
倍率(屈光度) -0.75(0.05) 0.00
中心厚度(mm) 0.127(0.005) 0.002
实施例4
从生产线上取样用浓度440ppm的K-90PVP处理并灭菌(124℃，大约18分钟)后的etafilcon A透镜，测量其直径、基弧、球面倍率和中心厚度并与未经处理的1-Day牌接触镜上的类似测量值相比较。列于表3中的数据表明K-90PVP不会明显地影响这些参数。
表3
 
处理后的 未经处理的
直径(mm) 14.24(0.04) 14.18(0.04)
基弧(mm) 8.94(0.03) 8.94(0.04)
与目标物的球面倍率偏差(屈光度) -0.01(0.04) -0.02(0.04)
与目标物的中心厚度偏差(mm) 0.000(0.004) 0.002(0.004)
实施例5
在表1的浓度下根据实施例1制备etafilcon A透镜。将处理后的透镜在9到50个患者的双盲研究中进行临床评估。患者双眼配戴该眼用透镜3-4天，并且在夜晚摘掉白天再戴上，配戴未经处理的1-Day牌接触镜3-4天并且在夜晚摘掉白天再戴上的患者作为对照。两种类型的透镜均不允许患者使用润滑液。采用问卷调查的方式要求患者给透镜评级。询问所有患者一系列有关总体喜好、舒适度喜好、每天结束配戴时间喜好、以及干燥度的问题。在其答案中要求其区分是否较为喜欢处理后的透镜、1-Day对照透镜、二者都喜欢还是都不喜欢。结果列于表4和5中。竖栏中的数字表示对四个选项之一给出正面评价的患者百分比。数字“n”表示针对特别样品类型的患者数量。“DNT”表示没有测试，n/a表示没有实用性。数字表明用大约500ppm浓度下的K-90PVP处理后的透镜对眼睛来说具有良好的临床舒适度。样品#指表1中的样品编号。
表4
Figure S06804880320070816D000082
表5
干燥度喜好％                每天结束配戴时间喜好％
 
样品# n PVP处理后的 1-Day 都喜欢 都不喜欢 PVP处理后的 1-Day 都喜欢 都不喜欢
1 9 33 33 11 0 56 22 44 0
2 37 24 43 22 8 27 43 27 5
 
3 41 32 51 17 2 29 49 17 2
4 10 20 40 30 10 20 10 60 10
5 41 20 46 32 2 20 41 37 2
6 31 42 24 38 0 38 35 16 6
7 42 36 19 38 3 41 24 40 0
8 41 27 22 49 7 22 24 41 7
9 48 38 21 46 0 33 19 44 0
10 45 24 20 58 4 18 20 51 4
实施例6
利用实施例1的方法用500ppm的K-90PVP处理etafilcon A接触镜。将处理后的透镜用磷酸盐缓冲的盐溶液简单清洗，并将清洗后的透镜置于模仿人眼尺寸的细胞培养多孔板(Cellgrow XL)的孔中。参见Farris RL，Tear Analysisin Contact Lens Wears，Tr.Am.Opth.Soc.Vol.LXXXIII，1985。向各个板孔中加入四百微升磷酸盐缓冲的盐溶液(KH2PO4 0.20g/L，KCl 0.20g/L，NaCl 8.0g/L，Na2HPO4[无水]1.15g/L)。盖上板孔并将多孔板存放于35℃下的暖箱中。
在不同的时间将三个透镜从暖箱中取出并通过HPLC分析测定PVP是否释放到了磷酸盐缓冲的盐溶液中。平均值结果表示于表6种。PVP量的极限为20ppm。该测试并未在分析样品中检测到任何PVP。该数据表明PVP在大于20ppm的水平下不释放。
表6
 
时间 释放的PVP
30分 <20ppm
1小时 <20ppm
2小时 <20ppm
4小时 <20ppm
8小时 <20ppm
16小时 <20ppm
24小时 <20ppm

Claims (21)

1.一种提供聚合的眼用透镜的方法，包括：在聚合后用包含100ppm至3000ppm润湿剂的包装溶液加热聚合的眼用透镜至大于50℃且最高达150℃的温度，并且聚合的眼用透镜配方在聚合前不包含所述润湿剂，其中包装溶液还包含3700ppm硼酸钠，其中润湿剂为聚乙烯吡咯烷酮。
2.权利要求1的方法，其中聚乙烯吡咯烷酮的K值为K-60到K-120。
3.权利要求1的方法，其中聚乙烯吡咯烷酮的K值为K-85到K-95。
4.权利要求1的方法，其中聚乙烯吡咯烷酮的K值为K-90。
5.权利要求1的方法，其中润湿剂包含K值为K-85至K-95的聚乙烯吡咯烷酮，并且其中加热在大于120℃的温度。
6.权利要求1的方法，其中聚合的眼用透镜与浓度400至440ppm的K值为K-90的聚乙烯吡咯烷酮在124℃加热18分钟。
7.权利要求1的方法，其中聚合的眼用透镜与浓度300至400ppm的K值为K-90的聚乙烯吡咯烷酮在121℃加热30分钟。
8.权利要求7的方法，其中加热步骤在单独密封接触镜包装中进行。
9.权利要求6的方法，其中加热步骤在单独密封接触镜包装中进行。
10.权利要求5的方法，其中眼用透镜选自acofilcon A，alofilcon A，alphafilcon A，amifilcon A，astifilcon A，atalafilcon A，balafilcon A，bisfilcon A，bufilcon A，comfilcon，crofilcon A，cyclofilcon A，darfilcon A，deltafilcon A，deltafilcon B，dimefilcon A，drooxifilcon A，epsifilcon A，esterifilcon A，etafilcon A，focofilcon A，genfilcon A，govafilcon A，hefilcon A，hefilcon B，hefilcon D，hilafilcon A，hilafilcon B，hioxifilcon B，hioxifilcon C，hixoifilcon A，hydrofilcon A，lenefilcon A，licryfilcon A，licryfilcon B，lidofilcon A，lidofilcon B，lotrafilcon A，lotrafilcon B，mafilcon A，mesifilcon A，methafilcon B，mipafilcon A，nelfilcon A，netrafilcon A，ocufilcon A，ocufilcon B，ocufilcon C，ocufilcon D，ocufilcon E，ofilcon A，omafilcon A，oxyfilcon A，pentafilcon A，perfilcon A，pevafilcon A，phemfilcon A，polymacon，silafilcon A，siloxyfilcon A，tefilcon A，tetrafilcon A，trifilcon A，以及xylofilcon A。
11.权利要求5的方法，其中眼用透镜选自genfilcon A，lenefilcon A， lotrafilcon A，lotrafilcon B，balafilcon A，comfilcon，etafilcon A，nelfilcon A，hilafilcon，以及polymacon。
12.权利要求5的方法，其中眼用透镜选自etafilcon A，nelfilcon A，hilafilcon，以及polymacon。
13.权利要求5的方法，其中眼用透镜选自etafilcon A。
14.权利要求7的方法，其中眼用透镜是etafilcon A接触镜。
15.权利要求1的方法，其中聚合的眼用透镜在所述包装溶液中加热所述透镜之前是未水合的。
16.权利要求15的方法，其中聚乙烯吡咯烷酮具有K-60至K-120的K值。
17.权利要求16的方法，其中聚乙烯吡咯烷酮具有K-60至K-90的K值。
18.权利要求15的方法，所述方法还包括用含有第二润湿剂的第二部分溶液加热权利要求15的未水合聚合的眼用透镜的第二步骤。
19.权利要求18的方法，其中润湿剂是K值在K-60的聚乙烯吡咯烷酮，所述第二润湿剂是K值在K-90的聚乙烯吡咯烷酮。
20.权利要求18的方法，其中润湿剂是K值在K-90的聚乙烯吡咯烷酮，所述第二润湿剂是K值在K-90的聚乙烯吡咯烷酮。
21.权利要求19的方法，其中K值在K-60的聚乙烯吡咯烷酮的浓度在30000 ppm到150000 ppm之间，并且K值在K-90的聚乙烯吡咯烷酮的浓度在100 ppm到500 ppm之间。
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