CN114377199A - 植骨组合物 - Google Patents
植骨组合物 Download PDFInfo
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- CN114377199A CN114377199A CN202111125714.1A CN202111125714A CN114377199A CN 114377199 A CN114377199 A CN 114377199A CN 202111125714 A CN202111125714 A CN 202111125714A CN 114377199 A CN114377199 A CN 114377199A
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Abstract
本发明提供一种植骨组合物，包含有约50‑70％重量比的陶瓷颗粒，其中该陶瓷颗粒包含有磷酸三钙与生物活性玻璃；以及约30‑50％重量比的载体。载体提供良好的操作性与可塑性，使植骨组合物以不同形状填补于人体中，通过高占比的陶瓷颗粒，在植入人体之后，载体于短时间内降解，陶瓷颗粒仍可形成生长支架，利于新生骨细胞贴附与生长，也加速了骨缺损伤口的愈合。
Description
技术领域
本发明为关于一种医疗用人体植入物，特别是指一种植骨组合物。
背景技术
骨移植(bone graft)是骨科临床上相当常见的手术之一，其主要是为了修补在各种情况下所造成的骨缺损(bone defect)，例如四肢骨折、骨头病变、骨头病变手术切除以及关节置换与修复等等。进行骨植入的材料主要有三种：自体骨、异体骨和人工合成骨。自体骨具有最好的骨生成(osteogenesis)、骨传导(osteoconduction)和骨诱导(osteoinduction)三种作用，是最好的植入材料，但是会有需要病人取骨的问题。异体骨虽然具有良好的骨诱导效果，但是需要有经过配对的捐赠者或捐赠骨，并且术后仍有发炎或排斥反应的风险。人工合成骨虽然不具有骨生成效果，但能有良好的骨传导作用和骨诱导效果，而且容易取得，在临床上也经常被使用。
人工合成骨主要是以磷、钙等一般骨组织中的主要化学成分所组成的生物活性颗粒所组成，通常为固定的颗粒状或块状型态，而实际手术应用时，骨缺损通常为不规则形，颗粒状和块状形态的人工合成骨不易填入骨缺损中，为方便医师进行手术操作，而有黏土块状或骨泥注射状的人工合成骨产品，医师可依照植入部位的大小和形状，抓取、揉捏和塑形人工合成骨并填入骨缺损中。
然而，市面上的人工合成骨往往具有生物兼容性不佳与降解太快的问题，导致所植入的人工合成骨无法与新骨细胞有效贴附之外，也无法在骨缺损内形成生长支架，导致骨缺损伤口的愈合情况不佳。
发明内容
有鉴于此，本发明的目的在于提供一种植骨组合物，其生物兼容性佳且能够有效的形成稳定且具有支撑性的结构。
为达成前述目的，本发明提供一种植骨组合物，包含有约50-70％重量比的陶瓷颗粒，其中该陶瓷颗粒包含有磷酸三钙与生物活性玻璃；以及约30-50％重量比的载体。
由此，本发明所提供的植骨组合物，具有高占比的陶瓷颗粒，并且含有磷酸三钙与生物活性玻璃，磷酸三钙能够促进新生骨细胞贴附生长，而生物活性玻璃能够诱导生长因子并促进新生骨细胞增生，因此在植入人体之后，纵使载体于短时间内降解，陶瓷颗粒仍可形成生长支架，利于新生骨细胞贴附与生长，也加速了骨缺损伤口的愈合。
附图说明
图1与图2为本发明所使用的磷酸三钙颗粒在电子显微镜下的影像图。
图3为本发明进行动物试验，于术后3个月牺牲之后取得骨缺损植入部位的组织染色图，其中A、B为实验组，C、D为对照组，E、F为空白组，图中标注的NB为新骨，TA为残余材料。
图4为本发明进行动物试验，于术后6个月牺牲之后取得骨缺损植入部位的组织染色图，其中A、B为实验组，C、D为对照组，E、F为空白组，图中标注的NB为新骨，TA为残余材料。
具体实施方式
为使本公开的目的、技术方案和优点更加清楚明白，以下结合具体实施例，对本公开进一步详细说明。
以下列举几个不同的实施例以及实验例，详细说明本发明所提供的植骨组合物。
制备磷酸三钙
将微米(μm)等级的磷酸三钙(tricalcium phosphate，TCP)与纤维素衍生物溶液，例如纤维素乙酸酯、纤维素硝酸酯、纤维素甲醚、纤维素乙醚等，混合搅拌2分钟，再加入粒径小于1.18毫米(mm)的萜类化合物颗粒，例如胡萝卜素、樟脑、松香酸、薄荷醇等，混合后继续搅拌10分钟造粒，在1000-1200℃下烧结18小时后，由No.6筛网和No.35筛网筛分出粒径为0.2-3.0毫米的磷酸三钙颗粒样品。
使用扫描电子显微镜(FEI Inspect S)照射前述流程所制备的磷酸三钙颗粒并分析影像如图1、2所示，可知这些磷酸三钙颗粒样品的微孔尺寸范围为100-500微米。
进一步使用孔隙仪(MatsuHaku，GP-120C)，利用媒介法，以水为介质量测孔隙度，对三批磷酸三钙采样量测，得出这些磷酸三钙颗粒样品的孔隙率分别为76.74±0.51％、81.75±1.43％和82.86±0.36％。
实施例一
70℃水浴中，将所有载体混合之后，再加入陶瓷颗粒，以重量比50％的陶瓷颗粒与50％的载体混合搅拌10分钟之后，冷却至室温。其中，陶瓷颗粒的成份包含有占整体重量比40％的磷酸三钙以及10％的生物活性玻璃(bioactive glasses)，此时磷酸三钙与生物活性玻璃的重量比比例为1∶0.25，所使用的磷酸三钙系依照前述流程所制备，粒径大小为约0.2至3毫米，且孔隙率大于等于约70％，而载体的成份包含有占整体重量比15％的甘油(glycerol)、25％的聚乙二醇(polyethylene glycol，PEG)、5％的羧甲基纤维素(carboxymethyl cellulose，CMC)以及5％的水。
根据参考文献(R.Cross，“Elastic and viscous properties of Silly Putty”，Am.J.Phys.80，870-875(2012))所提供的测试方法，进行弹性与粘性的验证，本测试使用万能试验机(Cometech，QC-505M2F)进行样品压缩变形与样品压力值的收集。首先在万能试验机上安装上压板、下压板及力值传感器，再将依照前段流程与配比所制作的植骨组合物塑型成直径为14±2毫米且高度为30±2毫米的圆柱状测试片后固定于下压板上，将力值传感器归零后，以单一速度每分钟15毫米(mm/min)对测试片进行7毫米的压缩位移。计算机记录压缩过程中测试片的回馈力值与压缩位移的距离，再将数据转换为应力(stress)-应变(strain)曲线图，其中应力值等于回馈力值除以压缩面积，应变值等于压缩位移除以原测试片高度，而抗压模量等于应力(stress)-应变(strain)曲线图中压缩曲线的斜率。
依照上述测试方法，本实验例中测试片的抗压模量为0.290百万帕斯卡(MPa)，此时测试人员揉捏的手感柔软、容易塑型且操作性佳。
实施例二
70℃水浴中，将所有载体混合之后，再加入陶瓷颗粒，以重量比55％的陶瓷颗粒与45％的载体混合搅拌10分钟之后，冷却至室温。其中，陶瓷颗粒的成份包含有占整体重量比15％的磷酸三钙以及40％的生物活性玻璃，此时磷酸三钙与生物活性玻璃的重量比比例为1∶2.66，所使用的磷酸三钙系依照前述流程所制备，粒径大小为约0.2至3毫米，且孔隙率大于等于约70％，而载体的成份包含有占整体重量比20％的甘油、23％的聚乙二醇、2％的羧甲基纤维素以及0％的水。
根据前述实施例一中所详述的测试方法，对依照前段流程与配比所制作的植骨组合物进行弹性与粘性的验证，本实验例中测试片的抗压模量为0.110百万帕斯卡，此时测试人员揉捏的手感柔软、容易塑型且操作性佳。
实施例三
70℃水浴中，将所有载体混合之后，再加入陶瓷颗粒，以重量比55％的陶瓷颗粒与45％的载体混合之后，冷却至室温。其中，陶瓷颗粒的成份包含有占整体重量比45％的磷酸三钙以及10％的生物活性玻璃，此时磷酸三钙与生物活性玻璃的重量比比例为1∶0.22，所使用的磷酸三钙系依照前述流程所制备，粒径大小为约0.2至3毫米，且孔隙率大于等于约70％，而载体的成份包含有占整体重量比18％的甘油、25％的聚乙二醇、2％的羧甲基纤维素以及0％的水。
根据前述实施例一中所详述的测试方法，对依照前段流程与配比所制作的植骨组合物进行弹性与粘性的验证，本实验例中测试片的抗压模量为0.512百万帕斯卡，此时测试人员揉捏的手感柔软、容易塑型且操作性佳。
实施例四
70℃水浴中，将所有载体混合之后，再加入陶瓷颗粒，以重量比65％的陶瓷颗粒与35％的载体混合之后，冷却至室温。其中，陶瓷颗粒的成份包含有占整体重量比25％的磷酸三钙以及40％的生物活性玻璃，此时磷酸三钙与生物活性玻璃的重量比比例为1∶1.6，所使用的磷酸三钙系依照前述流程所制备，粒径大小为约0.2至3毫米，且孔隙率大于等于约70％，而载体的成份包含有占整体重量比12％的甘油、10％的聚乙二醇、3％的羧甲基纤维素以及10％的水。
根据前述实施例一中所详述的测试方法，对依照前段流程与配比所制作的植骨组合物进行弹性与粘性的验证，本实验例中测试片的抗压模量为0.224百万帕斯卡，此时测试人员揉捏的手感柔软、容易塑型且操作性佳。
实施例五
70℃水浴中，将所有载体混合之后，再加入陶瓷颗粒，以重量比70％的陶瓷颗粒与30％的载体混合之后，冷却至室温。其中，陶瓷颗粒的成份包含有占整体重量比10％的磷酸三钙以及60％的生物活性玻璃，此时磷酸三钙与生物活性玻璃的重量比比例为1∶6，所使用的磷酸三钙系依照前述流程所制备，粒径大小为约0.2至3毫米，且孔隙率大于等于约70％，而载体的成份包含有占整体重量比5％的甘油、18％的聚乙二醇、5％的羧甲基纤维素以及2％的水。
根据前述实施例一中所详述的测试方法，对依照前段流程与配比所制作的植骨组合物进行弹性与粘性的验证，本实验例中测试片的抗压模量为0.346百万帕斯卡，此时测试人员揉捏的手感柔软、容易塑型且操作性佳。
动物试验
取实施例四所制备而出的植骨组成物作为实验组的测试样品，含有占整体重量比69％生物活性玻璃、19％甘油和12％聚乙二醇的市售品作为对照组的测试样品。
取10只6个月大，体重3.5-4.5公斤的新西兰大白兔，区分为术后3个月与6个月各5只，其中再区分为实验组、对照组和空白组，以异氟醚气麻麻醉后，在股骨骨干处钻一个
毫米大小的孔洞，分别将实验组与对照组的样品填满植入在左股骨与右股骨的股骨髁(femoral condyles)处，空白组则不植入任何样品。术后伤口分层缝合，每周观察动物的外观、呼吸、反射、行为，在研究期间中并无发现动物有任何异状。每月量测动物的体重，在研究期间中体重均微幅上升或无显著变化，并无大幅度减轻的现象。术后3个月与6个月分别进行人道牺牲，取下股骨检体后，将检体置于75％的酒精中固定保存，再进行组织切片苏木素-伊红染色(H&E stain)。
术后3个月的组织切片影像如图3所示，实验组相较于对照组，组织切片图中有尺寸扩大与显著沉淀的新骨(NB)(图3A与图3B)，且实验组的残余材料(TA)与新骨紧密相连，显现实验组样品的生物兼容性良好，能与骨组织形成良好的键结。而缺损内的对照组样品降解并培养了新骨与些微的结缔组织(fibrous tissue)(图3C与图3D)，代表对照组样品植入体内后有发生免疫反应，由纤维结缔组织来完成修复，显现对照组测试物与骨组织的亲和性不高。而空白组具有特定的新骨生成与多层的脂肪组织(fat tissue)浸润(图3E与图3F)。
术后6个月的组织切片影像如图4所示，实验组样品在缺损内已大部分降解，生成增厚与分支的层状新生骨(图4A与图4B)，其中图4B显示实验组样品已溶解并形成层状新生骨。对照组样品在缺损内已大部分降解，周边形成层状新生骨与多层的脂肪细胞(图4C与图4D)，其中图4D显示对照组样品已被吞噬细胞溶解并被结缔组织包覆，显现对照组降解较快，导致空槽处由脂肪组织所填满，而非新骨组织的增生。空白组有破碎的层状新生骨与丰富的脂肪组织浸润(图4E与图4F)。
透过上述动物实验可知，就新骨生成方面来看，经比对多张组织切片影像，相较于空白组，术后6个月实验组与对照组均有显著的新骨生成。其中，实验组又比对照组诱导较多的新骨生成，具有显著性差异。而就材料降解而言，经比对多张组织切片影像，发现术后6个月的实验组材料残余较对照组材料残余多，能于骨缺损内持续提供生物支架。
综合上述实施例、动物试验及其结论与详细说明，在本发明所提供的植骨组合物中，陶瓷颗粒的总占比高达50-70％，并且含有磷酸三钙与生物活性玻璃，磷酸三钙能够促进新生骨细胞贴附生长，而生物活性玻璃能够诱导生长因子并促进新生骨细胞增生，因此在植入人体之后，纵使载体于短时间内降解，陶瓷颗粒仍可以形成生长支架，有利于新生骨细胞贴附与生长，也加速了骨缺损伤口的愈合。再者，本发明所使用的磷酸三钙具有高孔隙率以及适当粒径，能够增加孔洞的空间，有助于新生骨细胞的进入与生长。最后，在具有高占比陶瓷颗粒的同时，本发明所提供的载体成分与配比使得植骨组成物保留了较佳的操作性，而依照上述测试流程，发现抗压模量在约0.110至0.512百万帕斯卡之间的时候，测试人员揉捏塑型时候的手感柔软、容易塑型且操作性佳，能够方便医师在临床手术时进行塑型，提升了使用上的便利性。
以上所述的具体实施例，对本公开的目的、技术方案和有益效果进行了进一步详细说明，所应理解的是，以上所述仅为本公开的具体实施例而已，并不用于限制本公开，凡在本公开的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本公开的保护范围之内。
Claims (8)
1.一种植骨组合物，包含有：
约50-70％重量比的陶瓷颗粒，其中该陶瓷颗粒包含有磷酸三钙与生物活性玻璃；以及
约30-50％重量比的载体。
2.根据权利要求1所述的植骨组合物，其中该磷酸三钙与该生物活性玻璃的配比为重量比约1∶0.22至1∶6。
3.根据权利要求1所述的植骨组合物，其中该磷酸三钙的粒径大小为约0.2至3毫米。
4.根据权利要求3所述的植骨组合物，其中该磷酸三钙的孔隙率系大于等于约70％。
5.根据权利要求1所述的植骨组合物，其中该载体包含有甘油、聚乙二醇以及羧甲基纤维素。
6.根据权利要求5所述的植骨组合物，其中该载体更包含有水。
7.根据权利要求1所述的植骨组合物，其中各材料的配比为重量比约5-20％甘油、10-25％聚乙二醇、2-5％羧甲基纤维素以及0-10％水。
8.根据权利要求1所述的植骨组合物，其中该植骨组合物的抗压模量为约0.110-0.512百万帕斯卡。
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110059178A1 (en) * | 2009-09-08 | 2011-03-10 | Musculoskeletal Transplant Foundation Inc. | Tissue Engineered Meniscus Repair Composition |
| US20140271785A1 (en) * | 2013-03-14 | 2014-09-18 | Prosidyan, Inc. | Bioactive porous bone graft implants |
| US20150072017A1 (en) * | 2013-09-09 | 2015-03-12 | Olympus Biotech Corporation | Carrier materials for protein delivery |
| WO2019173457A1 (en) * | 2018-03-06 | 2019-09-12 | Prosidyan, Inc. | Osteostimulative, bioactive and flowable bone void filler |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1323986C (zh) * | 2006-03-20 | 2007-07-04 | 天津大学 | CaO－P2O5－Na2O－MgO玻璃增强多孔β－磷酸三钙生物陶瓷制备方法 |
| US8288344B2 (en) * | 2007-03-15 | 2012-10-16 | Musculoskeletal Transplant Foundation | Ceramic composition for filling bone defects |
| US9925301B2 (en) * | 2012-04-06 | 2018-03-27 | Trustees Of Tufts College | Methods of producing and using silk microfibers |
| US10016529B2 (en) * | 2015-06-10 | 2018-07-10 | Globus Medical, Inc. | Biomaterial compositions, implants, and methods of making the same |
| CN107412852A (zh) * | 2017-07-26 | 2017-12-01 | 山东冠龙医疗用品有限公司 | 骨水泥组合物及其套组 |
| US12151050B2 (en) * | 2018-03-01 | 2024-11-26 | Tepha, Inc. | Medical devices containing compositions of poly(butylene succinate) and copolymers thereof |
-
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-
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110059178A1 (en) * | 2009-09-08 | 2011-03-10 | Musculoskeletal Transplant Foundation Inc. | Tissue Engineered Meniscus Repair Composition |
| US20140271785A1 (en) * | 2013-03-14 | 2014-09-18 | Prosidyan, Inc. | Bioactive porous bone graft implants |
| CN105246519A (zh) * | 2013-03-14 | 2016-01-13 | 普罗斯蒂安公司 | 生物活性多孔骨移植植入物 |
| US20150072017A1 (en) * | 2013-09-09 | 2015-03-12 | Olympus Biotech Corporation | Carrier materials for protein delivery |
| WO2019173457A1 (en) * | 2018-03-06 | 2019-09-12 | Prosidyan, Inc. | Osteostimulative, bioactive and flowable bone void filler |
Non-Patent Citations (2)
| Title |
|---|
| （美）斯勒茨基等: "《腕关节外科学 高级理论与手术技巧》", 31 December 2011, 北京：人民军医出版社 * |
| NOEL DAVISON ET AL: "In vivo performance of microstructured calcium phosphate formulated in novel water-free carriers", 《ACTA BIOMATERIALIA》 * |
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