CN1265846C - 一种基于磷酸钙/硫酸钙的骨移植组合物 - Google Patents

一种基于磷酸钙/硫酸钙的骨移植组合物 Download PDF

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CN1265846C
CN1265846C CNB028091949A CN02809194A CN1265846C CN 1265846 C CN1265846 C CN 1265846C CN B028091949 A CNB028091949 A CN B028091949A CN 02809194 A CN02809194 A CN 02809194A CN 1265846 C CN1265846 C CN 1265846C
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J·J·库珀
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Abstract

一种骨移植组合物，包含硫酸钙，缓慢溶解的钙源，以及正磷酸盐和氢氧根离子。该组合物可以是粉末状或颗粒状。

Description

一种基于磷酸钙/硫酸钙的骨移植组合物
本发明涉及一种骨移植组合物，以及一种骨移植物成形的方法。
在整形外科和牙外科应用方面，对于可生物相容和生物再吸收的移植材料，有着巨大的需求，因为它们能够方便、有效地作为骨替代物使用。包括由于牙周疾病、脊增生、窦的升高所造成的骨损失、由于损伤、疾病或外科手术以及脊柱软化造成的骨缺陷或腔孔。在随后移植过程中，骨替代物在一定时间范围内与充满生机的新生骨头一样完全被吸收。
骨移植材料优选自体移植物，即患者自身的骨头，因为它具备完全的生物相容性，不会导致排斥反应或是疾病的传染，并且具有良好的成骨能力。可是，它的来源受到限制，需要另外的外科操作并且经常存在捐赠点不健全的问题。
通常来说，同种异体移植骨由于更易得到以及效率更高而被认为是一种可供选择的方法，然而它有传染疾病的潜在可能，且因为是“外来”的组织，而存在着免疫反应的可能。此外，特别是原料的来源(经常是患骨质疏松的老年人)和制备的多样性而导致材料不同，特性各异。这使得在使用同种异体移植物时难以预测临床效果，因此治疗延误常常会引起并发症。
本发明提供了一种骨移植组合物，该组合物包括硫酸钙和缓慢可溶性的钙源，正磷酸盐和氢氧根离子。
这些离子的来源优选由缓慢水溶性化合物提供，并且优选室温下溶解度小于5克/升的化合物，更优选小于1克/升，最优选小于0.1克/升的化合物。
钙离子可以单独来源于硫酸钙，或可以由一种或多种碳酸钙、磷酸钙、氧化钙、氟化钙、柠檬酸钙、硬脂酸钙或石灰岩提供。
硫酸钙可以是二水合物、半水合物、可溶性的无水石膏或不溶性的无水石膏的形态。组合物中硫酸钙与所有其余化合物的比例优选0.2-2重量份。
组合物中也可以包含一种药物，优选能有效治疗的用量。药物可以包括任一的：一种抗生素，一种抗癌剂，或一种骨形态蛋白。
正磷酸根离子可以有一种或多种来源：羟基磷灰石，α磷酸三钙、β磷酸三钙、磷酸二钙、磷酸四钙或正磷酸镁。正磷酸根离子的来源可以是微多孔颗粒状固体形式。颗粒的尺寸为0.2-5.0毫米。正磷酸盐的来源可以是微多孔颗粒状固体混合物形式。
氢氧根离子有一种或多种来源：氧化钙、不溶性无水石膏、氢氧化钙、氧化镁、氢氧化镁、氧化锌、氢氧化锌或碱性碳酸镁。
组合物中正磷酸盐的碱性值优选0-1.0摩尔。
组合物可以是一种粉末，其中粉末能够与水或水性溶液混合以形成一种有用的糊状剂。
作为选择，组合物也可以是颗粒状或丸状的形式。组合物可以使用片剂挤压器形成丸状。
本发明也提供了一种形成骨移植物的方法，该方法包括利用以上10个段落中任一段落所述的骨移植组合物。
当处于粉末状时，使用前组合物可以与水或水性溶液混合以形成一种油灰或糊状剂。油灰或糊状剂可以通过适当的工具如注射器涂布到手术位点上。或者油灰或糊状剂可以涂布到模具中并在施用到手术位点之前固化。
组合物处于颗粒或丸状时，颗粒或药丸可以被裹入骨腔。
本发明根据下面所描述的实施例而得以具体体现。
实施例1
一种根据下述组成制备而成的粉末状混合物：
1.25克β-磷酸三钙
0.63克α-半水合硫酸钙
0.05克氧化镁
β-磷酸三钙颗粒大小为250-500微米。
混合物与0.85毫升1％的硫酸钾溶液混匀，以期形成糊状剂而用来填充牙周缝隙。
实施例2
一种根据下述组成制备而成的粉末状混合物：
35.0克粒径为1-2毫米的β-磷酸三钙颗粒
17.5克二水合硫酸钙
2.2克氧化镁
0.80克硬脂酸钙
利用片剂挤压器将混合物压成直径为3毫米，深2.5毫米的药丸。这些药丸被用来填充入骨腔之中。
实施例3
一种根据下述组成制备而成的粉末状混合物：
35.0克α-磷酸三钙
14.0克不溶形态的无水硫酸钙
10.0克碱性碳酸镁
0.1克氧化锌
利用片剂挤压器将混合物挤压成药丸。
实施例4
一种根据下述组成制备而成的粉末状混合物：
10.0克β-磷酸三钙颗粒
5.0克α-半水合硫酸钙粉末
0.5克氧化镁
β-磷酸三钙颗粒的大小为1-2毫米。
混合物与9.5毫升的水混匀后被压入直径为6毫米的圆柱状模具中，在模具中固化。固化药丸从模具中取出后加以干燥。这些药丸被用来填充骨腔。
实施例5
一种由先前实施例(实施例4)的方法制备的粉末状混合物，但包含有5％重量的抗生素庆大霉素，它是在成型前加入到粉末混合物中。
以下描述了一种骨移植组合物和一种使用骨移植组合物的方法，该方法有许多优点。这种组合物是基于下面的化学方程式：
组合物提供了一种离子的来源，这些离子在体内沉积下来可以形成一种粗结晶的替代磷灰石，与目前其它可利用的合成骨移植替代品相比，用磷灰石作替代品更能够模拟处于天然矿化阶段的骨。而且，这种反应与人体重新长出新的、健康的骨的能力是相称的。沉淀的羟基磷灰石适于骨折后的再吸收。硫酸钙相最初通过简单的分解机理经过数周时间再吸收表现为一种大孔状的适应于血管的分布以及新生骨组织侵入的结构。硫酸钙成为一种微孔状的屏障，阻止不必要的软组织(细胞)在移植过程期间侵入。
正磷酸盐离子的来源优选微多孔状颗粒的固体，其大小为0.2-5毫米，这样的粒径范围提供了颗粒间100-200微米的孔隙，这对于细胞的滤过、血管扩张刺激新骨的生长来说是必要的。
可以作出各种修改而不背离本发明的范围。钙离子可以仅来源于硫酸钙，也可以从实施例2中的硬脂酸钙中获取，或者是其它含钙的化合物，如碳酸钙、磷酸钙、氧化钙、氟化钙、柠檬酸钙或石灰岩。此外，或者作为可选择地，正磷酸盐离子可源于β-磷酸三钙，也可由羟基磷灰石、α-磷酸三钙、磷酸二钙、磷酸四钙或正磷酸镁来提供这些离子。
实施例中氢氧根离子的来源是氧化镁，也可以是实施例3中的氧化锌。这些离子尽管是附加的，或是从氧化钙，不溶性无水石膏，氢氧化钙，氢氧化镁，氢氧化锌或碱性碳酸镁中获得。如实施例所示，硫酸钙可以一种或多种下述形式存在：α-半水合物，β半水合物、可溶性的无水石膏或不溶性的无水石膏或二水合物。
组合物可以包含一种有效治疗用量的药物，其中药物包括有抗生素、抗癌剂或是骨形态蛋白。
尽管在以上的说明书中，已经描述了本发明所具有的极其重要的特征，然而应当认为，无论申请人是否加以强调，其请求保护的关于其中的任何可获得专利的特征或是具有这些特征的化合物，都已在权利要求书中有所涉及。

Claims (23)

1.一种骨移植组合物，所述组合物包含硫酸钙；以及缓慢可溶性钙离子源、正磷酸根离子源和氢氧根离子源，这些离子源由室温下水溶解度低于5克/升的化合物提供；其特征在于氢氧根离子源可以是以下一种或多种：氧化钙、不溶性无水石膏、氢氧化钙、氧化镁、氢氧化镁、氧化锌、氢氧化锌或碱性碳酸镁。
2.如权利要求1所述的组合物，其特征在于化合物在室温下的水溶解度低于1克/升。
3.如权利要求2所述的组合物，其特征在于化合物在室温下的水溶解度低于0.1克/升。
4.如权利要求1所述的组合物，其特征在于氢氧根离子源和正磷酸根离子源不是钙盐，钙离子源仅仅是硫酸钙。
5.如权利要求1所述的组合物，其特征在于钙离子源由一种或多种以下物质提供：碳酸钙，磷酸钙，氧化钙，氟化钙，柠檬酸钙，硬脂酸钙或石灰岩。
6.如权利要求1所述的组合物，其特征在于硫酸钙是一种或多种以下形式：二水合物，半水合物，可溶性无水石膏或不溶性无水石膏。
7.如权利要求1所述的组合物，其特征在于硫酸钙与组合物中所有其它化合物的比例以重量计为0.2∶1-2∶1。
8.如权利要求1所述的组合物，其特征在于组合物含有一种药物。
9.如权利要求8所述的组合物，其特征在于药物以有效治疗用量存在。
10.如权利要求8所述的组合物，其特征在于药物包含以下任一种：抗生素，抗癌剂或骨形态蛋白。
11.如权利要求1所述的组合物，其特征在于正磷酸根离子源是以下一种或多种：α-磷酸三钙、β-磷酸三钙、磷酸二钙、磷酸四钙或正磷酸镁。
12.如权利要求1所述的组合物，其特征在于正磷酸根离子源是微多孔颗粒状固体形式。
13.如权利要求12所述的组合物，其特征在于颗粒的粒径范围是0.2-5.0毫米。
14.如权利要求1所述的组合物，其特征在于组合物中碱度与正磷酸盐的摩尔比为0.0∶1-1.0∶1。
15.如权利要求1所述的组合物，其特征在于组合物是一种粉末形式，其中粉末能够与水或水性溶液混合以形成一种糊状剂。
16.如权利要求1所述的组合物，其特征在于组合物是颗粒或者丸剂的形式。
17.如权利要求16所述的组合物，其特征在于使用片剂挤压器将组合物成型为丸状。
18.一种形成骨移植物的方法，其特征在于这种方法包含使用上述任一权利要求所述的骨移植组合物。
19.如权利要求18所述的方法，其特征在于使用前将粉末状的组合物与水或水性溶液混合以形成一种油灰或者糊状剂。
20.如权利要求19所述的方法，其特征在于油灰或者糊状剂通过涂药器涂布到手术位点。
21.如权利要求20所述的方法，其特征在于油灰或者糊状剂通过注射器涂布到手术位点。
22.如权利要求19所述的方法，其特征在于油灰或者糊状剂被涂布到模具中，并在施用到手术位点之前固化。
23.如权利要求18所述的方法，其特征在于当组合物是颗粒或者丸剂的形式时，颗粒或者丸剂可以被裹入骨腔中。
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Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE520688C2 (sv) * 2000-04-11 2003-08-12 Bone Support Ab Ett injicerbart ersättningsmaterial för benmineral
SE517168C2 (sv) * 2000-07-17 2002-04-23 Bone Support Ab En komposition för ett injicerbart ersättningsmaterial för benmineral
US8496955B2 (en) 2001-05-02 2013-07-30 Biocomposites Limited Calcium phosphate/sulfate-based bone implant composition
SE522098C2 (sv) * 2001-12-20 2004-01-13 Bone Support Ab Ett nytt benmineralsubstitut
AU2003236068B2 (en) * 2002-06-19 2006-09-07 Dr. H.C. Robert Mathys Stiftung Hydraulic cement based on calcium phosphate for surgical use
SE0300620D0 (sv) * 2003-03-05 2003-03-05 Bone Support Ab A new bone substitute composition
EP1680089B1 (en) 2003-10-22 2013-09-11 Lidds AB Composition comprising biodegradable hydrating ceramics for controlled drug delivery
SE0302983D0 (sv) * 2003-11-11 2003-11-11 Bone Support Ab Anordning för att förse spongiöst ben med benersättnings- och/eller benförstärkningsmaterial och förfarande i samband därmed
SE527528C2 (sv) 2004-06-22 2006-04-04 Bone Support Ab Anordning för framställning av härdbar massa samt användning av anordningen
KR100759718B1 (ko) 2004-12-21 2007-10-04 요업기술원 수열 열간 가압법을 이용한 인산칼슘계 다공체 및 그 제조방법
WO2006089380A1 (fr) * 2005-02-24 2006-08-31 Roland Dricot Implant osseux
BRPI0617086B8 (pt) 2005-09-09 2021-06-22 Agnovos Healtcare Llc cimento composto substituto de enxerto ósseo e artigos dele originados
WO2008109165A2 (en) * 2007-03-07 2008-09-12 New York University Mineralized guided bone regeneration membranes and methods of making the same
US8685432B2 (en) 2008-03-25 2014-04-01 University Of Utah Research Foundation Controlled release tissue graft combination biomaterials
JP2012526144A (ja) * 2009-05-06 2012-10-25 ラボラトリー スキン ケア インコーポレイテッド 活性物質−リン酸カルシウム粒子複合体を含む経皮送達組成物およびその使用方法
GB2470401A (en) 2009-05-22 2010-11-24 Bpb Ltd Calcium sulphate-based products having enhanced water resistance
EP2453844B1 (en) * 2009-07-16 2020-09-02 The Curators Of The University Of Missouri Scaffolds with trace element for tissue regeneration in mammals
CA2784533C (en) * 2009-12-18 2016-02-09 Howmedica Osteonics Corp. Post irradiation shelf-stable dual paste direct injectable bone cement precursor systems and methods of making same
EP2523566B1 (en) * 2010-01-12 2018-08-29 Mars, Incorporated Multi-component pet food comprising solid component formed by compression tableting
US9180137B2 (en) 2010-02-09 2015-11-10 Bone Support Ab Preparation of bone cement compositions
US20120028204A1 (en) * 2010-08-02 2012-02-02 Lazarou Spiros A Correction of alveolar cleft with calcium-based bone graft materials
WO2012054009A1 (en) * 2010-10-19 2012-04-26 Jiin-Huey Chern Lin Method for preparing a hardened calcium sulfate dihydrate block and use thereof
US10182973B2 (en) 2010-11-10 2019-01-22 Stryker European Holdings I, Llc Polymeric bone foam composition and method
US9889235B2 (en) 2013-02-05 2018-02-13 University Of Utah Research Foundation Implantable devices for bone or joint defects
JP6352947B2 (ja) 2013-02-20 2018-07-04 ボーナ スーポート アーベー 硬化性骨代替物の硬化改善
ITMI20130636A1 (it) * 2013-04-18 2014-10-19 Novagenit S R L Metodo per la preparazione di biomateriali biocompatibili e biodegradabili a base di collagene e granuli di idrossiapatite/¿-tricalcio fosfato per uso in chirurgia ortopedica e biomateriali così ottenuti
US10118827B2 (en) * 2013-05-10 2018-11-06 Reed A. Ayers Combustion synthesis of calcium phosphate constructs and powders doped with atoms, molecules, ions, or compounds
EP3964216B1 (en) * 2018-04-23 2024-03-06 Moroxite T AB Novel treatment approach by targeted delivery of bioactive molecules bio modulated ceramics
CN109549954B (zh) * 2018-12-13 2020-09-04 中国科学院深圳先进技术研究院 一种磷基材料制剂及其制备方法和应用
CN110558311A (zh) * 2019-09-17 2019-12-13 海南医学院第一附属医院 一种创战伤中保存离体骨的医用材料及其制备方法
CN110496245A (zh) * 2019-09-17 2019-11-26 彭磊 一种治疗骨髓炎的医用材料及其制备方法
CN112043862A (zh) * 2020-09-14 2020-12-08 香港大学深圳医院 一种具有自固化功能的镁缓释骨水泥及其制备方法
CN114375968B (zh) * 2022-01-24 2023-09-26 河南科技大学 一种自固化无毒抗菌材料及其制备方法和应用

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4778471A (en) * 1986-11-19 1988-10-18 University Of Dayton Zcap ceramics
JP2529613B2 (ja) 1990-03-09 1996-08-28 学校法人松本歯科大学 硬化性組成物
US5149368A (en) * 1991-01-10 1992-09-22 Liu Sung Tsuen Resorbable bioactive calcium phosphate cement
NO940913L (no) 1993-03-26 1994-09-27 Bristol Myers Squibb Co Preparater for kontrollert frigivelse av biologisk aktiv TGF-
JPH078548A (ja) 1993-06-24 1995-01-13 Mitsui Toatsu Chem Inc 硬化性生体用粉材
GB9407135D0 (en) * 1994-04-11 1994-06-01 Aberdeen University And Plasma Treatment of osteoporosis
AU3795395A (en) * 1994-11-30 1996-06-06 Ethicon Inc. Hard tissue bone cements and substitutes
US6224635B1 (en) * 1998-11-06 2001-05-01 Hospital For Joint Diseases Implantation of surgical implants with calcium sulfate
DE19853832A1 (de) 1998-11-21 2000-05-25 Merck Patent Gmbh Polyalkensäuren enthaltende Calcium-Phosphatzemente

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