CN102834122A - 制备聚醚醚酮抗微生物植入物的方法 - Google Patents

制备聚醚醚酮抗微生物植入物的方法 Download PDF

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CN102834122A
CN102834122A CN2010800635847A CN201080063584A CN102834122A CN 102834122 A CN102834122 A CN 102834122A CN 2010800635847 A CN2010800635847 A CN 2010800635847A CN 201080063584 A CN201080063584 A CN 201080063584A CN 102834122 A CN102834122 A CN 102834122A
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zeolite
peek
implant
silver
antimicrobial
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CN102834122B (zh
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J.J.克鲁登
J.哈菲斯
J.E.迪顿
J.R.佩珀
D.约翰斯
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Abstract

公开了制造具有抗微生物性质的可植入医疗装置(优选用PEEK)的方法。抗微生物作用通过以下产生：将含有抗微生物金属阳离子的陶瓷微粒掺入熔融PEEK树脂内，接着让其冷却并固化于通过注塑、切割和机械加工或其它技术实现的其最终形状。

Description

制备聚醚醚酮抗微生物植入物的方法
 
本申请要求2009年12月11日提交的美国临时申请序列号61/285,719和2010年2月2日提交的61/300,629的优先权，其公开内容通过引用结合到本文中。
背景
由于各种原因将可植入的医疗装置植入体内，包括整形术(如髋关节置换、脊柱疗法、膝关节置换、骨折修复等)。考虑到此类装置的结构完整性要求，制造的材料有限，常规包括金属、塑料和复合物。
这些装置带来的益处经常被感染抵消，感染可导致败血症和死亡。引起感染的最常见生物体是表皮葡萄球菌(Staphylococcus epidermidis)和金黄色葡萄球菌(Staphylococcus aureus)。其它革兰氏阳性细菌、革兰氏阴性细菌和真菌生物体也成问题。特别关注的是耐甲氧西林金黄色葡萄球菌(MRSA)，一类对许多抗生素耐药的葡萄球菌。因此，MRSA感染比普通葡萄球菌感染更难治疗，已成为严重的问题。
许多病原菌可在生物工程植入物上形成多细胞涂层，称为生物膜。生物膜可通过提供稳定的保护环境促进微生物的增殖和传播。这些生物膜，当充分产生时，可散播细菌浮游涌溢(shower)，其可引起广泛的全身感染。
生物工程材料为形成细菌生物膜充当良好的宿主。有时，植入物本身携带感染生物体，植入物产生由感染生物体接种的非常顽固的生物膜。当这发生时，通常必须取出植入物，必须用一种或多种抗生素延长疗程治疗患者以努力治愈感染，然后再植入新植入物。这显然让患者遭受另外的创伤和痛苦，且非常昂贵。
因此，已进行许多研究以防止细菌和真菌生物体在整形植入物表面上定殖，通过使用抗微生物剂比如抗生素与此类装置采用的材料表面结合。例如，银是强效的天然抗生素，并预防感染。作为催化剂，它使单细胞细菌、病毒和真菌的氧代谢需要的酶失效。它们使人酶或部分人体化学窒息，而不对它们产生相应的危害。结果是在体内引起疾病的生物体的破坏。银破坏细菌膜、膜间酶和DNA转录。
陶瓷比如沸石发挥阳离子笼的功能，能够负载银及其它具有抗微生物性质的阳离子。金属沸石可用作抗微生物剂，比如通过与用作热塑材料的树脂混合以制备可植入装置，或作为涂层应用于装置；见例如美国专利号6,582,715，其公开内容通过引用结合到本文中。抗微生物金属沸石可通过用铵离子和抗微生物金属离子替换沸石中全部或部分离子可交换离子而制备。优选并非所有离子可交换离子都被替换。
已发现可用于植入物的一种具体热塑树脂是聚醚醚酮(PEEK)。这种热塑聚合物具有芳族主链，通过酮和醚官能度互联。PEEK适合植入物因为其模量与骨的密切相配，且耐受化学和放射损伤。批准用于植入的PEEK等级非常纯和惰性，在允许植入哺乳动物之前需要通过严格的细胞毒性测试。
ISO 10993设定在临床研究之前评估医疗装置生物相容性必需的一系列标准。这些文件的前言是三方协议且是医疗装置安全使用评估的协调的一部分。这些标准包括：
· ISO 10993-1: 2003 Biological evaluation of medical devices Part 1: Evaluation and testing (医疗装置的生物学评估第1部分: 评估和测试)
· ISO 10993-2: 2006 Biological evaluation of medical devices Part 2: Animal welfare requirements (医疗装置的生物学评估第2部分: 动物福利要求)
· ISO 10993-3: 2003 Biological evaluation of medical devices Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity (医疗装置的生物学评估第3部分: 对遗传毒性、致癌性和生殖毒性的测试)
· ISO 10993-4: 2002/Amd 1: 2006 Biological evaluation of medical devices Part 4: Selection of tests for interactions with blood (医疗装置的生物学评估第4部分: 对血液相互作用测试的选择)
· ISO 10993-5: 2009 Biological evaluation of medical devices Part 5: Tests for in vitro cytotoxicity (医疗装置的生物学评估第5部分: 对体外细胞毒性的测试)
· ISO 10993-6: 2007 Biological evaluation of medical devices Part 6: Tests for local effects after implantation (医疗装置的生物学评估第6部分: 对植入后局部作用的测试)
· ISO 10993-7: 1995 Biological evaluation of medical devices Part 7: Ethylene oxide sterilization residuals (医疗装置的生物学评估第7部分: 环氧乙烷灭菌残留物)
· ISO 10993-8: 2001 Biological evaluation of medical devices Part 8: Selection of reference materials (医疗装置的生物学评估第8部分: 参考材料的选择)
· ISO 10993-9: 1999 Biological evaluation of medical devices Part 9: Framework for identification and quantification of potential degradation products (医疗装置的生物学评估第9部分: 对潜在降解产物的鉴定和量化的框架) 
· ISO 10993-10:2002/Amd 1: 2006 Biological evaluation of medical devices Part 10: Tests for irritation and delayed-type hypersensitivity (医疗装置的生物学评估第10部分: 对刺激和迟发型超敏反应的测试)
· ISO 10993-11: 2006 Biological evaluation of medical devices Part 11: Tests for systemic toxicity (医疗装置的生物学评估第11部分: 对全身毒性的测试)
· ISO 10993-12: 2007 Biological evaluation of medical devices Part 12: Sample preparation and reference materials (医疗装置的生物学评估第12部分: 样品制备和参考材料)(只有英文可用)
· ISO 10993-13: 1998 Biological evaluation of medical devices Part 13: Identification and quantification of degradation products from polymeric medical devices (医疗装置的生物学评估第13部分: 聚合物医疗装置降解产物的鉴定和量化)
· ISO 10993-14: 2001 Biological evaluation of medical devices Part 14: Identification and quantification of degradation products from ceramics (医疗装置的生物学评估第14部分: 陶瓷降解产物的鉴定和量化)
· ISO 10993-15: 2000 Biological evaluation of medical devices Part 15: Identification and quantification of degradation products from metals and alloys (医疗装置的生物学评估第15部分: 金属和合金降解产物的鉴定和量化)
· ISO 10993-16: 1997 Biological evaluation of medical devices Part 16: Toxicokinetic study design for degradation products and leachables (医疗装置的生物学评估第16部分: 对降解产物和可浸出物的毒物代谢动力学研究设计)
· ISO 10993-17: 2002 Biological evaluation of medical devices Part 17: Establishment of allowable limits for leachable substances (医疗装置的生物学评估第17部分: 对可浸出物建立可允许限度)
· ISO 10993-18: 2005 Biological evaluation of medical devices Part 18: Chemical characterization of materials (医疗装置的生物学评估第18部分: 材料的化学表征)
· ISO/TS 10993-19: 2006 Biological evaluation of medical devices Part 19: Physio-chemical, morphological and topographical characterization of materials (医疗装置的生物学评估第19部分: 材料的物理-化学、形态学和局部解剖学表征)
· ISO/TS 10993-20: 2006 Biological evaluation of medical devices Part 20: Principles and methods for immunotoxicology testing of medical devices (医疗装置的生物学评估第20部分: 医疗装置免疫毒理学测试的原理和方法)。
在高加工温度，如果金属沸石不是非常干燥，则可释放水分。这种水分可导致聚合物熔体中形成空隙，可促成PEEK聚合物分解，和掺入沸石抗微生物剂的金属，比如银、铜和/或锌的氧化。虽然空隙的存在对某些非承重应用而言可能不是关键，但不存在空隙对承重应用比如脊柱修复而言是关键的。
如果掺入金属沸石的过程在空气中进行，随着温度上升可出现严重氧化，水分和氧与金属离子接触。银将迅速变暗至暗褐色或黑色。而且，将显著量金属沸石掺入PEEK聚合物可影响组合物的粘度和流变学。
本公开内容基于以下发现，即在高温和高剪切的条件下，可以将抗微生物剂沸石比如银沸石掺入PEEK内，比如通过将掺杂的金属沸石混入熔融PEEK (熔点为300-400℃, 取决于纯度)内，接着将复合共混物模塑和加工。结果是提供具有有效抗微生物活性的医疗装置比如植入物以减少细菌的生长和感染的风险。
概述
本公开已克服现有技术的缺点，本公开涉及制造具有抗微生物性质的可植入医疗装置(优选用PEEK)的方法。抗微生物作用通过以下产生：将含有抗微生物金属阳离子的陶瓷微粒掺入熔融PEEK树脂内，接着让其冷却并固化于通过注塑、切割和机械加工或其它技术实现的其最终形状。
金属离子的释放速率受塑料负载含金属离子的陶瓷微粒和陶瓷材料负载金属的程度支配。在血液和体液中的电解质浓度相对恒定，将引起与比如银、铜和锌及其它来自植入物表面的离子的离子交换，其灭活或杀死革兰氏阳性和革兰氏阴性生物体，包括大肠杆菌和金黄色葡萄球菌。例如，在4%或更大的金属沸石浓度实现微生物6-log减少的有效抗微生物控制。装置可植入动物，特别是人。特别预期脊柱植入物。
附图简述
图1是某些实施方案的颈部间隔物的透视图。
详述
本文公开的实施方案涉及将陶瓷，优选沸石，作为阳离子笼与医疗植入物组合加工以递送或给予一种或多种抗微生物阳离子。除了沸石以外，其它合适的陶瓷抗微生物材料包括羟磷灰石、磷酸锆及其它离子交换陶瓷。
合适的阳离子包括银、铜、锌、汞、锡、铅、金、铋、镉、铬和铊离子，及其组合，优选银、锌和/或铜。天然沸石或合成沸石都可用于制备用于本文公开实施方案的沸石。
“沸石”是具有三维骨架结构的铝硅酸盐，由下式表示：XM2/nO·Al2O3·YsiO2·ZH2O其中M表示可离子交换的离子，一般是单价或二价金属离子，n表示(金属)离子的原子价，X和Y分别表示金属氧化物和二氧化硅的系数，Z表示结晶水的数目。此类沸石的实例包括A-型沸石、X-型沸石、Y-型沸石、T-型沸石、高二氧化硅沸石、方钠石等。
此外，可将硅酸盐材料比如金属掺杂的磷酸盐玻璃，生物活性玻璃比如45S5和BG加工以递送合适剂量的抗微生物阳离子。
下列方法和处理条件为加工具有期望性质的抗微生物PEEK植入物所需。
材料处理
PEEK是高熔点材料，具有大约340℃的熔点，必须在360℃-400℃加工才能够掺入金属沸石粉并使复合共混物挤出或模塑。在这些高温下，任何截留水分的释放都可引起聚合物熔体中形成空隙。这可促成PEEK聚合物的分解和掺入沸石抗微生物剂内的金属的氧化，减小抗微生物剂功效。另外，空隙的存在可明显降低终产物的性质。对于制备用于承重脊柱植入物的材料，将任何空隙的大小和数目减到最小对维持终产物的机械性质是关键的。因此，重要的是从用于制备植入物、PEEK和抗微生物粉(复合共混物组分)的原料除去残留水分。应将银沸石粉在大气压加热至约400℃，在此保持足够时间以使结合水释放。如果使粉末薄薄地扩散，则水分释放将更有效，30-60分钟保持时间合适。也可在低温减压干燥银沸石。优选在加工之前将复合共混物组分在干净环境中干燥至小于0.1%重量水分。而且，在加工之前和期间必须维持材料在无水环境中。
抗微生物粉末非常吸湿，在任何使用之前需要将材料密封在其原来的包装中。在预共混操作期间对环境空气的暴露必须最小。作为额外预防措施，在负载之前和之后必须即刻将进料粉末料斗用干燥氮气吹扫。
在进行任何混合操作之前必须将PEEK材料在120℃-130℃干燥12小时(或在同等时间/温度)。这确保在加工之前PEEK粒料的残留水分小于0.1%重量水分。
加工后包装：在混合后需要立即将材料包装在防潮袋中。
混合设备
为实现高一致性程度，可用双螺杆挤出机将PEEK与所需添加剂共混。刚好在进入挤出机螺杆之前将添加剂通过重量计量加入熔融PEEK内以获得期望的添加剂负载。双螺杆挤出的使用改善填料分布和浸湿，导致更可再现的流变学性能。
用于混合的优选设备的具体实例描述如下：
挤出线: 30 mm 
螺杆设计: 30-3 
模头设置: 2孔 
粒料长度的可接受范围(英寸): 0.100-0.135
粒料直径的可接受范围(英寸): 0.085-0.120。
一种合适的挤出机是Leistritz ZSE双螺杆挤出机。
压缩模塑
可用压缩模塑法制备适合二级机械加工操作的接近网形混合的PEEK坯料。压缩模塑是将预热的混合PEEK聚合物粒料或预制品在加压、加热模腔中模塑为预定形状的方法。压缩模塑是适合模塑复杂形状的高容量、高压力方法。和机械加工装置相比，这种方法耗费相对少的来自挤出棒的材料。
机械加工
可通过用机械加工法比如翻转、钻孔、打眼、研磨、绞孔、锯、削、刨和/或铰除去材料将PEEK植入物制备成最终形状。这些机械加工法可以是手动或通过使用计算机控制的机械加工中心自动化。
所有聚合材料的导热性都低于金属，所以在机械加工期间迅速积累热。如果钻头冷却并在较低速率运转可实现更干净的切割和更开放的表面。在将材料机械加工成植入物时如果PEEK表面温度明显上升则机械加工的PEEK表面可被弄脏和“剥皮”，可能影响阳离子的释放。为了优化混合PEEK表面光洁度，期望干净切割和“开放的”表面结构。一种实现期望的表面光洁度的方法是用干净的冷压缩空气冷却切割工具，结合优化的工具切割速度和进料速率。而且，冷却速率对PEEK的结晶度可具有显著作用，这对优化金属离子的释放速率可能是关键的。通过调节制造期间的冷却速率，小心地控制植入物材料的结晶度百分数。
在PEEK材料上的机械加工和抛光操作容易传播残留应力。在机械加工之前，推荐将从PEEK形成的组件退火以缓解应力。在机械加工或抛光期间，可通过在切割点局部加热在材料内建立进一步的应力。因此，如果将在组件上进行大量机械加工和抛光，可能需要第二次退火程序。基于退火过程(除去应力或热历史或者优化结晶结构)的期望结果，应当要求和遵循由PEEK材料制造商推荐的退火过程。
可通过将机床专门“只用于PEEK”和将机床置于具体专用于医疗级PEEK机械加工的制造设备区，而采取额外预防措施来防止机械加工的混合PEEK装置的表面污染。
注射模塑
可用注射模塑法制造抛光或明显抛光的混合PEEK装置。注射模塑法用混合PEEK聚合物制备部件，通过将混合PEEK粒料进料到加热的桶(400℃)内，其中将熔融的混合PEEK混合，压入维持在约175℃-205℃温度的加热模腔内。一旦注入模内，熔融的混合PEEK冷却至低于343℃的温度，硬化为模腔的形状。通过监测和密切控制模的期望温度(约175℃-205℃)设定点，可实现部件特征和容限控制的显著增加和表面剥皮的最小化。
最佳沸石负载
金属沸石掺入树脂内的量还应当是有效促进抗微生物活性的量；如足量以预防或抑制生长和消灭细菌和真菌生物体。同时将显著量的金属沸石掺入peek聚合物熔体内可影响组合物的粘度和流变学。因此，建立允许负载足量沸石而不对终产物的堆积性质产生不利影响的加工窗口。 
沸石在树脂中的合适量是约0.01-20.0 wt.%。发现最佳负载是0.1-约10.0 wt.%。用最佳负载条件制备的粒料的紧密控制和监测的尺度在下文表I显示。如果在高温过程期间出现严重氧化或水分接触金属离子，则抛光的粒料颜色是重要指示。纯PEEK是淡棕色，而适当加工的含沸石PEEK是褐色。在已出现氧化的情况下，银将迅速变暗为暗褐色或黑色。
表I: 平均粒料长度和直径。
沸石负载 平均粒料直径(英寸) 平均粒料长度(英寸) 颜色
0.5% 0.090 0.126 褐色
1.0% 0.093 0.127 褐色
2.0% 0.093 0.127 褐色
4.0% 0.091 0.125 褐色
包埋沸石的确认
样品的扫描电镜(SEM)揭示沸石微粒在复合物中令人满意地均匀分散。SEM图像显示样品高负载，与目标负载率一致。
用热解定量确定银金属沸石的负载。将小的准确称重的PEEK/银沸石复合物样品置于陶瓷坩埚中，用丙烷火焰燃烧。用这种方法单纯PEEK完全烧尽不剩下残留物，而负载金属沸石的PEEK将烧掉剩下粉状残留物。然后可通过重量确定银沸石负载的量。可通过从残留物提取银并通过石墨炉AA或ICP确定提取溶液中的银量确认存在的银量。
被洗脱的银的量化
通过化学分析用石墨炉原子吸收光谱确定不同负载率样品的可洗脱的离子银含量。将1”x1”样品试样浸入40 ml 0.8%硝酸钠溶液内持续24小时。从不同负载洗脱的银量在表II列出。
表II: 从不同负载条件洗脱的银量
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。
可类似地确定其它抗微生物金属的洗脱。
抗微生物功效
当材料的表面暴露于微生物攻击时，掺入熔融PEEK内的银或其它金属沸石将显示足够的抗微生物控制并非不言而喻。用革兰氏阴性(大肠杆菌)和革兰氏阳性(金黄色葡萄球菌)微生物进行细菌攻击测试，测试两种不同的负载(2%和4%)。结果显示对于两种生物体，在暴露24小时后4%负载有效控制细菌的菌落形成单位(CFU)。如表III强调，经过所述时间段后，不含任何沸石的对照样品显示无细菌减少，而4%负载显示微生物减少至少6 log。
表III: 抗革兰氏阴性和革兰氏阳性生物体的抗微生物功效。
沸石负载 测试生物体 CFU平均减少
0% (对照样品) 大肠杆菌 无减少
2% 大肠杆菌 77.0%
4% 大肠杆菌 99.9992%
0% (对照样品) 金黄色葡萄球菌 无减少
2% 金黄色葡萄球菌 30.5%
4% 金黄色葡萄球菌 99.9998%
射线不透性
PEEK植入物的一个缺点是，由于PEEK的射线透射性，用PEEK制备的植入装置在X-射线图像中显示不良。因此，从X-射线鉴定植入物的精确定位和完整性和观察其它重要特征可能困难。已用于克服这种缺点的一种方法是将硫酸钡加入混合的混合物中。虽然由于将硫酸钡加入PEEK可使装置不透射线，但为了期望的射线不透性添加所需量的硫酸钡容易减弱所得装置的强度。因此，使用从硫酸钡和PEEK组合物制备的植入物在装置的期望机械性质与其射线不透性之间提供不期望的折衷。本文公开的材料在x-射线下观察时即使在银沸石低负载水平也展示不透射线性。这是在不牺牲材料的抗微生物功效或机械完整性的情况下可产生的重要的额外益处。
增强的细胞附着
植入物表面的沸石可明显增加成骨细胞附着，因为在沸石中存在带负电荷的硅酸盐。PEEK产品的显著缺点经常是，由于PEEK的固有惰性，在植入物部位缺乏细胞粘附。通过植入物表面上带负电荷的硅酸盐的可用性，可适当减轻这个问题。沸石结构固有地带负电荷。这些硅酸盐吸引包含RGD肽序列(具有正确的确认)的蛋白质，导致形成骨的成骨细胞的附着和增殖。这启动级联过程最终导致显著骨生长。
表面糙度优化
PEEK很难渗透水分，所以只有不深于沸石微粒直径的表层材料将可进行银洗脱。如果在该区域的银失活或者转化为不溶性复合物，则材料可能作为抗微生物材料完全无效。因此需要小心地监测和遵循加工条件以维持植入物表面上的银功效。可通过用ICP测量可洗脱的银并确保该水平充分高于0.1 ppm银的报道的最小生物膜生长抑制浓度，来定量监测功效。已显示20 ppb银在实验室有效，且制剂在低于5 ppb显示抗微生物活性。而且，虽然体积溶液浓度可能是5 ppb，但靠近表面的阳离子的活性必定更好。
表面颜色也可用作监测加工条件的定性度量。失活或者转化的银的颜色将从褐色变为黑色或者黑色-褐色混合物。
另外，可优化表面糙度以改善植入物的成骨性质。体外研究已显示，进行骨生长的所有参数(粘附, 增殖, 碱性磷酸酶活性, 骨基质蛋白的合成和矿化)似乎受到材料表面抛光的影响。常用制造技术比如喷砂(喷珠、喷沙、喷苏打、低温喷CO2等)、用惰性材料刮擦或砂磨可用于控制表面糙度以优化银洗脱和细胞生长两者。原子力显微镜(AFM)或轮廓扫描仪可用于计算以纳米计的平均表面糙度，可将该数值与体外细胞测试结果的骨生长参数关联以得到表面糙度的最佳范围。
血管形成的增加
早期腰椎和颈部间隔物在大多数情况下都具有单块构造。目的是建立同种异体移植骨皮质的聚合模拟物，这曾经是先前的融合的黄金标准。目前植入物设计的发展已朝向内与外表面之间的开口用于新骨块的血管形成。间隔物的腔是重要的，因为它接收外部材料(填料)，且可能是病原体的载体。已设计本文公开的植入物的柱以便它允许机械上坚固的植入物，同时增加血管形成途径，产生大的面积可用于银洗脱。
设计的具体实施例显示于图1。从该图可见，柱状设计允许表面积比单块构造明显增加。这导致明显增强的银洗脱曲线以及增加的血管形成途径。
增加孔隙度
如果期望，在某些实施方案中可使PEEK多孔，具有合适的孔隙度，包括50%-85%体积的孔隙度。可用孔形成剂比如氯化钠赋予孔隙度，以通过本领域已知的方法产生包含多个互联孔的多孔聚合物。平均孔径一般大于180微米直径，适当在约300-约700微米。
树脂强化
如果期望，在某些实施方案中可将PEEK用强化材料比如陶瓷或碳纤维强化。这可通过将强化材料分散在PEEK聚合物基质中制备，比如通过将可植入的PEEK聚合物与碳纤维双螺杆混合。所得碳纤维-强化产物可用于直接注塑最终装置和接近网的形状，或者可将其挤成原料形状用于机械加工。掺入纤维或其它合适的强化材料提供高耐磨性，12 GPa的杨氏模量(匹配骨皮质的模量)，提供足够强度以允许其用于非常薄的植入物设计，该设计将应力更有效地分配至骨。强化材料比如碳纤维掺入PEEK的量可变化，比如用于调节杨氏模量和弯曲强度。一种合适的量是30 wt.%碳纤维。

Claims (11)

1. 一种制备抗微生物植入物的方法，其包含将聚醚醚酮树脂加热至有效熔化所述树脂的温度，向所述熔融树脂内共混金属沸石，和冷却所述共混物。
2. 权利要求1的方法，其中所述有效熔化所述树脂的温度为约360-约400℃。
3. 权利要求1的方法，其中所述金属沸石包含银沸石。
4. 权利要求1的方法，其进一步包含在所述熔化步骤之前将所述树脂通过加热至约120-130℃温度而干燥以除去残留水分。
5. 权利要求1的方法，其进一步包含在所述共混步骤之前将所述沸石在约400℃温度干燥以除去残留水分。
6. 权利要求1的方法，其中所述共混步骤在双螺杆挤出机中进行。
7. 权利要求1的方法，其中向所述树脂内共混的沸石量为约0.01-约20.0 wt%。
8. 权利要求1的方法，其中所述聚醚醚酮为多孔性。
9. 权利要求8的方法，其中所述聚醚醚酮具有50%-85%体积的孔隙度。
10. 权利要求1的方法，其中将所述聚醚醚酮强化。
11. 权利要求10的方法，其中将所述聚醚醚酮用碳纤维强化。
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