CN110328950A - 用于细胞培养的容器膜及其制备方法 - Google Patents

用于细胞培养的容器膜及其制备方法 Download PDF

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CN110328950A
CN110328950A CN201910487220.4A CN201910487220A CN110328950A CN 110328950 A CN110328950 A CN 110328950A CN 201910487220 A CN201910487220 A CN 201910487220A CN 110328950 A CN110328950 A CN 110328950A
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高文定
吴亚飞
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LONG SHENG JIANGSU PHARMACEUTICAL PACKAGING MATERIAL Co Ltd
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Abstract

本发明公开了一种用于细胞培养的容器膜，其包括依次设置的热封层、核心层、耐候层和透气层，所述热封层、核心层、耐候层和透气层均是共聚物层，以及一种制备上述用于细胞培养的容器膜的方法，包括，预干燥、熔融、冷却定型、拉伸、在线测厚和冷却收卷；本发明的用于细胞培养的容器膜是一种阻隔性、耐候性、透氧率等性能优异以及对细胞培养具有极佳保护性的多层共挤膜。

Description

用于细胞培养的容器膜及其制备方法
技术领域
本发明涉及一种高分子材料制成的生物医药用薄膜，更具体地说，涉及一种用于细胞培养的容器膜及其制备方法。
背景技术
随着干细胞研究、再生医疗的飞速发展，细胞培养技术通过细胞培养获取大量体外细胞，目前已经广泛应用于生物学、医学、药学等各个领域。当前细胞培养常用的装置包括细胞培养皿、细胞培养瓶、细胞培养袋。常规的细胞培养皿或细胞培养瓶口径较大且密封性差，当细胞培养液体积过大时，容易溢出，造成细胞污染的机率增大。目前常用的高分子材质的细胞培养袋通过外界气体交换使氧分子层迅速溶解于培养液中，以满足细胞正常生长和代谢的需求，但是这种细胞培养袋在进液和取液过程中会出现相互污染情况，严重影响细胞的培养效果，同时由于热封性能欠佳、透气性不良等问题容易造成细胞液渗漏、细胞增殖数量下降等问题。
发明内容
本发明所要解决的技术问题在于针对上述现有技术中的不足，提供一种热封性、阻隔性、以及透气性能优良、对细胞培养具有极佳保护性的多层共挤容器膜。
为解决上述技术问题，本发明采用如下技术方案是：一种用于细胞培养的容器膜，一种用于细胞培养的容器膜，包括从上到下依次设置的：热封层、核心层、耐候层，所述热封层以重量计份包括如下成分：改性等规聚丙烯1-20份，线型低密度聚乙烯1-30份，茂金属低密度聚乙烯1-5份，防菌剂0.1-2份，助剂0.1-0.5份，氧化石墨烯0.2-0.5份，聚乙二醇月桂酸酯5-8份，纳米级无机颗粒0.1-0.7份。
优选的是，所述用于细胞培养的容器膜，还包括透气层。
优选的是，所述热封层以重量计份包括如下成分：改性等规聚丙烯1-20份，线型低密度聚乙烯1-30份，茂金属低密度聚乙烯1-5份，防菌剂0.1-2份，助剂0.1-0.5份，氧化石墨烯0.2-0.5份，聚乙二醇月桂酸酯5-8份，纳米级无机颗粒0.1-0.7份。
优选的是，所述纳米级无机颗粒包括纳米二氧化钛、纳米二氧化硅、金纳米颗粒或纳米碳酸钙中的一种或多种。所述纳米级无机纳米粒子的添加可以充分发挥各个无机纳米颗粒的协同作用，减少空气对流和水分子运动产生的热传导，有利于维持所述用于细胞培养容器膜的内部温度，极大提升热封层保温性能。
优选的是，所述改性等规聚丙烯以重量计份包括如下成分：等规聚丙烯1-100份，马来酰亚胺0.1-1份，二乙醇胺0.1-1份、天然沸石粉0.1-0.3份，纳米氧化锌0.1-2份、偏氯乙烯0.1-0.5份。
聚丙烯结构规整、结晶度高，具有优良的力学性能、耐热性能以及化学稳定性，但是由于其规整的化学结构造成其抗冲击强度较差，通过加入偏氯乙烯能够改善聚丙烯的抗冲击强度，提高薄膜的韧性、拉伸性能，而纳米氧化锌、偏氯乙烯的添加增强材料的热粘强度，进一步提高薄膜热封性、抗冲击性能。
优选的是，所述防菌剂为银离子化合物，所述银离子化合物包括三价银离子化合物或二价银离子化合物。
银离子化合物由于其中富含的银离子，通过抑制细菌细胞壁中肽聚糖的干扰，抑制多糖肽与四钛交联连结，从而使细胞壁失去完整性，在没有渗透压保护的作用下，对金黄色葡萄球菌、大肠杆菌、白色念球菌等细菌均有良好的抑制作用，进一步对细胞培养容器膜中的细胞培养环境起到防菌、保护作用，从而提高细胞的增殖速率。
优选的是，所述助剂包括乙烯-苯烯共聚物、乙烯-辛烯共聚物、丙烯酸-丙烯酸酯共聚物、乙烯-醋酸乙烯共聚物中的至少一种。
优选的是，所述核心层由中密度聚乙烯树脂和嵌段共聚聚丙烯组成，其中所述中密度聚乙烯树脂和嵌段共聚聚丙烯的质量百分比为50:60-90:20。
优选的是，制备所述耐候层的原料以重量计份包括如下成分：聚对苯二甲酸乙二醇酯7-10份、乙烯-醋酸乙烯共聚物2-6份、二甲基酰胺0.1-1份、微晶纤维素0.1-0.5份、硅藻土0.05-0.1份，纳米二氧化钛0.1-0.3份。
优选的是，所述透气层以重量计份包括如下成分：聚乙烯3-10份、邻苯二甲酸丁二酯1-8份、碳酸钙0.1-1份、二月桂酸二丁基锡1-3份、纳米二氧化钛0.1-0.6份、甲基羟乙基纤维素0.1-0.5份。
邻苯二甲酸丁二酯是一种密度低极性强的结晶化合物，有良好的力学性能，冲击强度是其他薄膜的3-5倍，耐油，耐脂肪，耐烯酸，耐碱，耐大多数溶剂以及优良的耐高、低温性能，通过在对苯二甲酸丁二酯中添加聚乙烯、甲基羟乙基纤维素，进一步降低复合材料的密度，低密度的材料可以提升薄膜的透气性能，同时，该材料可以有效抵挡紫外线，低细胞毒性，卫生安全性好，显著提高细胞培养的成活率。
优选的是，所述制备方法包括如下步骤：(1)将所述热封层、核心层、耐候层、透气层的原料在50-60℃预干燥30min，然后送入挤出系统；(2)200-300℃熔融2h；(3)共挤模头挤出熔融物料，冷却焜冷却定型形成薄膜厚片；(4)将薄膜厚片在80-90℃再预热处理后，进行横向和纵向拉伸3.0-4.0倍；(5)拉伸后的薄膜进行热定型后，在线测厚；(5)冷却，收卷得到所述容器膜。
本发明的有益效果是：
(1)该容器膜在原料上选择用4层或多层结构的多层共挤薄膜。4层或多层的结构使得该多层共挤薄膜具有优良的耐折性，耐油，耐脂肪，耐烯酸，耐碱，耐高、低温性能，并且透气性能好，可抵挡紫外线，材料为低细胞毒性，卫生安全性好，可以显著提高细胞培养的成活率。
(2)线型低密度聚乙烯与低密度聚乙烯相比，具有较高的软化温度和熔融温度、强度大、韧性好、耐热、耐寒等优点，同时还具有良好的耐环境应力开裂性，耐冲击强度，耐撕裂强度等性能，但是存在成型收缩率大、阻隔性能差，热变形温度不高等缺点，将改性等规聚丙烯、茂金属低密度聚乙烯和线型低密度聚乙烯共混能够克服聚丙烯和聚乙烯固有的缺点，性能上取长补短，增强聚丙烯和聚乙烯之间的相容性，进一步提高薄膜的弹性。
(3)改性等规聚丙烯通过马来酰亚胺在天然沸石粉的作用下形成共聚物，二乙醇胺具有优良的热封性、增强等规聚丙烯的热封性能，纳米氧化锌具有良好的防菌、抑菌性能，二乙醇胺具有高强度、抗撕裂等特点，通过加入偏氯乙烯能够提高材料的刚性与强度，提高薄膜的韧性、拉伸性能以及薄膜的刚性，薄膜通过改性改性等规聚丙烯、偏氯乙烯、马来酰亚胺、纳米氧化锌进行共混挤出，原料之间进行互补增强，使得薄膜热封性、抗冲击性能等得到很大的改善。
附图说明
图1为用于细胞培养容器膜的结构示意图。
附图标记说明：
1—热封层；2—核心层；3—耐候层；4—透气层；
具体实施方式
下面结合实施例对本发明做进一步的详细说明，以令本领域技术人员参照说明书文字能够据以实施。
实施例1
用于细胞培养的容器膜，包括从上到下依次设置的：热封层、核心层、耐候层，所述热封层以重量计份包括如下成分：
其中所述助剂为丙烯酸-丙烯酸酯共聚物，所述纳米级无机颗粒为纳米二氧化硅和纳米碳酸钙的混合物。
所述用于细胞培养的容器膜制备方法包括如下步骤：(1)将所述热封层、核心层、耐候层、透气层的原料在50-60℃预干燥30min，然后送入挤出系统；(2)200-300℃熔融2h；(3)共挤模头挤出熔融物料，用冷却焜冷却定型形成薄膜厚片；(4)将薄膜厚片在80-90℃再预热后，进行横向和纵向拉伸3.0-4.0倍；(5)拉伸后的薄膜进行热定型后，在线测厚；(5)冷却，收卷得到所述容器膜。
实施例2
用于细胞培养的容器膜，包括从上到下依次设置的：热封层、核心层、耐候层，所述热封层以重量计份包括如下成分：
其中所述助剂为乙烯-苯烯共聚物，所述纳米级无机颗粒为纳米二氧化钛和金纳米颗粒的混合物。
所述用于细胞培养的容器膜制备方法包括如下步骤：(1)将所述热封层、核心层、耐候层、透气层的原料在50-60℃预干燥30min，然后送入挤出系统；(2)200-300℃熔融2h；(3)共挤模头挤出熔融物料，用冷却焜冷却定型形成薄膜厚片；(4)将薄膜厚片在80-90℃再预热后，进行横向和纵向拉伸3.0-4.0倍；(5)拉伸后的薄膜进行热定型后，在线测厚；(5)冷却，收卷得到所述容器膜。
实施例3
用于细胞培养的容器膜，包括从上到下依次设置的：热封层、核心层、耐候层，所述热封层以重量计份包括如下成分：
其中所述助剂为乙烯-醋酸乙烯共聚物，所述纳米级无机颗粒为纳米碳酸钙、纳米二氧化硅、纳米金颗粒的混合物。
所述用于细胞培养的容器膜制备方法包括如下步骤：(1)将所述热封层、核心层、耐候层、透气层的原料在50-60℃预干燥30min，然后送入挤出系统；(2)200-300℃熔融2h；(3)共挤模头挤出熔融物料，用冷却焜冷却定型形成薄膜厚片；(4)将薄膜厚片在80-90℃再预热后，进行横向和纵向拉伸3.0-4.0倍；(5)拉伸后的薄膜进行热定型后，在线测厚；(5)冷却，收卷得到所述容器膜。
对比例1
与实施例2的材料以及制备工艺基本相同，唯一不同的是将改性聚丙烯改为聚丙烯。
对比例2
与实施例2的材料以及制备工艺基本相同，唯一不同的是不添加纳米级无机颗粒。
对比例3
与实施例2的材料以及制备工艺基本相同，唯一不同的是不添加茂金属低密度聚乙烯和线型低密度聚乙烯。
对比例4
与实施例2的材料以及制备工艺基本相同，唯一不同的是不添加聚乙二醇月桂酸酯、助剂以及氧化石墨烯。
实施例1-3以及对比例1-4制备的包装膜进行测试得到性能测试结果如下；
表中，各项性能的测试方法如下：
1.薄膜透氧率：按照GB/T 21529-2008标准测试。
2.热封强度、拉伸强度和断裂伸长率：按照GB/T13542.2-2009标准测试。
由上述性能测试结果可知：改性等规聚丙烯具有较好的机械强度和阻隔性能，线型低密度聚乙烯和茂金属低密度聚乙烯的共混改性，使得乙烯-丙烯共聚体均匀的分布于聚丙烯相中，破坏聚丙烯的结晶，从而改善薄膜的热封性能；一定比例的纳米级无机粒子、助剂、聚乙二醇月桂酸酯、氧化石墨烯的添加使得冷却、收卷后的薄膜更加柔韧，各个原料之间进行互补增强的协同效应进一步提高材料热封性能、韧性、拉伸性能以及薄膜的透氧率，从而提高细胞培养的成活率和细胞增殖率。
应当理解，本文所使用的诸如“具有”、“包含”以及“包括”术语并不排除一个或多个其它元件或其组合的存在或添加。
尽管本发明的实施方案已公开如上，但其并不仅仅限于说明书和实施方式中所列运用，它完全可以被适用于各种适合本发明的领域，对于熟悉本领域的人员而言，可容易地实现另外的修改，因此在不背离权利要求及等同范围所限定的一般概念下，本发明并不限于特定的细节。

Claims (10)

1.一种用于细胞培养的容器膜，其特征在于，包括从上到下依次设置的：热封层、核心层、耐候层，所述热封层以重量计份包括如下成分：改性等规聚丙烯1-20份，线型低密度聚乙烯1-30份，茂金属低密度聚乙烯1-5份，防菌剂0.1-2份，助剂0.1-0.5份，氧化石墨烯0.2-0.5份，聚乙二醇月桂酸酯5-8份，纳米级无机颗粒0.1-0.7份。
2.根据权利要求1所述的用于细胞培养的容器膜，其特征在于，还包括透气层。
3.根据权利要求1所述的用于细胞培养的容器膜，其特征在于，所述纳米级无机颗粒包括纳米二氧化钛、纳米二氧化硅、金纳米颗粒或纳米碳酸钙中的一种或多种。
4.根据权利要求1所述的用于细胞培养的容器膜，其特征在于，所述改性等规聚丙烯以重量计份包括如下成分：等规聚丙烯1-100份，马来酰亚胺0.1-1份，二乙醇胺0.1-1份、天然沸石粉0.1-0.3份，纳米氧化锌0.1-2份、偏氯乙烯0.1-0.5份。
5.根据权利要求1所述的用于细胞培养的容器膜，其特征在于，所述防菌剂为银离子化合物，所述银离子化合物包括三价银离子化合物或二价银离子化合物。
6.根据权利要1所述的用于细胞培养的容器膜，其特征在于，所述助剂包括乙烯-苯烯共聚物、乙烯-辛烯共聚物、丙烯酸-丙烯酸酯共聚物、乙烯-醋酸乙烯共聚物中的至少一种。
7.根据权利要求1所述的用于细胞培养的容器膜，其特征在于，所述核心层由中密度聚乙烯树脂和嵌段共聚聚丙烯组成，其中所述中密度聚乙烯树脂和嵌段共聚聚丙烯的质量百分比为50:60-90:20。
8.根据权利要求1所述的用于细胞培养的容器膜，其特征在于，所述耐候层以重量计份包括如下成分：聚对苯二甲酸乙二醇酯7-10份、乙烯-醋酸乙烯共聚物2-6份、二甲基酰胺0.1-1份、微晶纤维素0.1-0.5份、硅藻土0.05-0.1份，纳米二氧化钛0.1-0.3份。
9.根据权利要求2所述的用于细胞培养的容器膜，所述透气层以重量计份包括如下成分：聚乙烯3-10份、邻苯二甲酸丁二酯1-8份、碳酸钙0.1-1份、二月桂酸二丁基锡1-3份、纳米二氧化钛0.1-0.6份、甲基羟乙基纤维素0.1-0.5份。
10.一种制备权利要求1-9至中任意一项所述的用于细胞培养的容器膜的方法，其特征在于，所述制备方法包括如下步骤：(1)将所述热封层、核心层、耐候层、透气层的原料在50-60℃预干燥30min，然后送入挤出系统；(2)200-300℃熔融2h；(3)多层共挤模头挤出熔融物料，用冷却焜冷却定型形成薄膜厚片；(4)将薄膜厚片在80-90℃再预热后，进行横向和纵向拉伸3.0-4.0倍；(5)拉伸后的薄膜进行热定型后，在线测厚；(5)冷却，收卷得到所述用于细胞培养的容器膜。
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