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CN1058689C - Porous calcium phosphate cement containing pore-creating agent - Google Patents

Porous calcium phosphate cement containing pore-creating agent Download PDF

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CN1058689C
CN1058689C CN 98110645 CN98110645A CN1058689C CN 1058689 C CN1058689 C CN 1058689C CN 98110645 CN98110645 CN 98110645 CN 98110645 A CN98110645 A CN 98110645A CN 1058689 C CN1058689 C CN 1058689C
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calcium
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CN1193614A (en )
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刘昌胜
许卫军
沈卫
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华东理工大学
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Abstract

本发明涉及一种用于人体硬组织修复的多孔磷酸钙骨水泥,公开了一种含有成孔剂的多孔磷酸钙骨水泥的制备方法和应用。 The present invention relates to a porous calcium phosphate bone cement for repairing human hard tissue, discloses the preparation and application of a porous calcium phosphate bone cement containing a pore-forming agent. 本发明采用无毒的微溶性盐、酸式盐和碱式盐或无毒的表面活性剂作为成孔剂,利用成孔剂的成孔特性制备出多孔固化体,不改变磷酸钙骨水泥自行固化的特性,不改变固化后其水化产物主要为羟基磷灰石的成分,水化反应速率基本不变,孔径在100~300μm之间,主要集中在150~250μm之间,有利于骨组织及其它有机组织的长入,加速材料的降解,促进骨的快速愈合,是一种具有广阔应用前景的人体硬组织修复材料。 Pore ​​characteristics of the present invention uses a non-toxic sparingly soluble salt, acid salts and base salts or nontoxic surfactant as a pore former, by using porogens prepared porous cured material, without changing its own calcium phosphate cement curing characteristics do not change after the curing component and the hydration product is predominantly hydroxyapatite, the hydration reaction rate substantially constant pore size between 100 ~ 300μm, mainly between 150 ~ 250μm, conducive to bone tissue and other organic tissue ingrowth, to accelerate the degradation of materials, and promote rapid healing of bone, is a kind of broad application prospects of human hard tissue repair material.

Description

含有成孔剂的多孔磷酸钙骨水泥及其应用 Porogen comprising a porous calcium phosphate bone cement and its Applications

本发明属于医用材料领域,涉及一种用于人体硬组织修复的多孔磷酸钙骨水泥及其应用。 The present invention belongs to the field of medical materials, relates to a porous calcium phosphate bone cement and its application for repairing human hard tissue.

磷酸钙骨水泥(简称CPC)是由几种磷酸钙盐组成的混合物,可以按常规的方法进行配制。 Calcium phosphate cement (the CPC) is a blend of several calcium salts thereof, may be formulated according to conventional methods. 其水化产物为羟基磷灰石,由于羟基磷灰石与脊椎动物的骨和牙齿的矿物成分非常相近,故其与人体组织的生物相容性好,因而通过几种磷酸钙盐的水化反应而生成的羟基磷灰石或人工合成的羟基磷灰石,常作为人体硬组织修复用的材料,它的研究和应用特别引入注目,近年来发展特别迅速。 Hydration product is hydroxyapatite, and hydroxyapatite mineral components since vertebrate bones and teeth are very close, so good biocompatibility with human tissue, thus by several hydrated calcium salt react to form synthetic hydroxyapatite or hydroxyapatite, often as a material for repairing human hard tissue, its research and applications, especially compelling, especially the rapid development in recent years. 目前在临床研究和应用上涉及较多的有以下几种:(1)按常规的方法进行配制磷酸钙骨水泥(CPC),用水调和后成糊状物,根据缺损部位任意填充塑型,并在人体环境和温度下自行固化,其最终成分转化为羟基磷灰石,这种水化形成的固化体的孔径<10μm。 Currently in clinical and research applications involving more of the following: (1) formulating calcium phosphate cement (CPC) according to a conventional method, to reconcile a paste with water, filled plastic according to any defect, and self-cure at ambient and body temperature, which is converted to the final composition of hydroxyapatite, such cured body aperture formed hydration <10μm. 动物实验表明:由于内部孔径小,磷酸钙骨水泥植入骨内后,早期只能与骨组织形成界面结合,它是靠组织长入植入物粗造不平的表明而形成的一种机械性锁和,强度不高,且由于骨组织无法长入,使磷酸钙骨水泥降解缓慢,而影响骨的改建。 Animal experiments show that: due to the small internal pore size, after implantation within bone calcium phosphate cement, the early bonding interface can be formed with the bone tissue, it is by tissue ingrowth implants showed an uneven roughness of a mechanically formed and lock, strength is not high, and not bone ingrowth since the slow degradation phosphate cement, affect bone remodeling.

(2)文献(KESalyer.,Plastic and Reconstructive Surgery,1989,84(2):236~244)报道的一种人工合成的羟基磷灰石陶瓷,是较为成功的一种人体硬组织修复用的材料,经过各国科学家多年的共同努力,已形成了多种成熟的制备方法:(US3929971)公开了它的制备技术,其它如气体分解法、浸渍法、水热热压法、有机质填充法、微波工艺法、蜡复型法等。 (2) Document (KESalyer, Plastic and Reconstructive Surgery, 1989,84 (2):. 236 ~ 244) a synthetic hydroxyapatite ceramic reported a more successful human hard tissue repairing material after years of efforts States scientists have formed a variety of mature preparation: (US3929971) discloses its preparation techniques, such other gas decomposition method, a dipping method, a hydrothermal hot pressing method, organic filler, microwave technology method, the wax replica method or the like. 它们是将碱性条件下形成的磷灰石加热到800-1200℃制得的。 They apatite is formed under alkaline conditions is heated to 800-1200 ℃ obtained. 这种工合成的羟基磷灰石陶瓷,具有有利于新骨向材料内部的快速生长,增加材料同宿主骨之间的界面结合强度的150~500μm的孔径,其共同特点是必须经过高温烧结步骤,高温烧结是导致颗粒间连接而产生强度、并产生多孔的必要条件。 This work synthetic hydroxyapatite ceramic having conducive to rapid growth of new bone within the material, to increase the aperture 150 ~ 500μm interface between host bone material in combination with the strength, the common feature is a high temperature sintering step must be , leading to inter-particle sintering temperature generated connection strength, and generates a necessary condition porous. 这种加热过程会引起磷灰石晶体的烧结,形成不被吸收的植入体,以致使它的应用受到了限制。 This heating process causes the sintered apatite crystals formed implant is not absorbed, so that its application has been limited.

(3)(US4869906)公开了通过高温烧结的方式产生多孔的磷酸钙盐小球,用作丙烯酸类骨水泥的填充料的技术,多孔颗粒内的孔径成为丙烯酸自由基聚合后固化体的孔径,所述方法也因为需要高温烧结而受到了限制。 (3) (US4869906) discloses the production of porous calcium phosphate sintered pellets by way of a high temperature, is used as filler technology acrylic bone cement, the pore size of the porous particles become free-radical polymerization of acrylic aperture cured body, the method also requires a high temperature sintering as limited. 因此,加速新骨长入和材料降解的用于骨缺损修复的材料依然是困扰外科医生的棘手问题。 Therefore, to accelerate new bone ingrowth and degradation of materials for bone defect repair material remains a thorny problem for the surgeon.

本发明的目的在于公开一种含有成孔剂的多孔磷酸钙骨水泥,利用成孔剂的成孔特性而制备出多孔固化体,避免因高温烧结而形成不被吸收的植人体,以解决骨缺损的修复的难题。 Object of the present invention is to disclose a pore-forming agent comprising a porous calcium phosphate bone cement, using a pore-forming agent to prepare a characteristic pore porous cured, to avoid high-temperature sintering to form a body implant is not absorbed to address bone repair of defect problems.

本发明的构思是这样的:1.利用微溶盐在水溶液中具有一定的溶解度的特性可制备多孔磷酸钙骨水泥。 Concept of the present invention is: 1. have a certain solubility in aqueous solutions using a sparingly soluble salt characteristics may be prepared porous calcium phosphate bone cement. 把微溶盐均匀地与磷酸钙骨水泥粉末搅合在一起,当磷酸钙骨水泥固化时,微溶盐占据固化体的部分空间,从而形成一个独立的单元,植入体内后,经过体液的不断渗透和清洗,由于体液中离子浓度积(Ksp)小于微溶盐的Ksp,微溶盐逐步被溶解,于是就形成了多孔结构。 After the sparingly soluble salt with calcium phosphate cement to uniformly mix together powder, calcium phosphate cement when cured, part of the space occupied by a sparingly soluble salt of a cured body, so as to form a single unit, implanted in the body after the body fluid constant infiltration and cleaning, since the body fluids ion product (Ksp) of less than Ksp sparingly soluble salt, a sparingly soluble salt is gradually dissolved, so it forms a porous structure. 其孔径的分布和大小由微溶盐的粒径控制。 And the pore size distribution is controlled by the particle size of the sparingly soluble salt. 这种材料在骨组织不断长入的同时才逐步形成多孔的,所以它的初始强度是很高的,克服了单纯多孔材料植到体内后初期强度较低的不良影响。 Such materials have evolved continuously at the same time the bone tissue ingrowth porous, so that its initial strength is high, implanted into the body to overcome the adverse effects of a lower initial strength porous material alone.

2.利用产气物质制备多孔磷酸钙骨水泥,将酸式盐和碱式盐加入到磷酸钙骨水泥粉末中。 2. Preparation of porous material using a gas phosphate cement, acid salts and base salts are added to the calcium phosphate cement powder. 当混合粉末同水接触调成浆体以后,酸式盐和碱式盐发生反应而产生气体:浆体内部产生气体从而形成多孔,固化以后形成多孔磷酸钙骨水泥。 When the powder is mixed with water into contact with the slurry, acid salts and base salts react to produce gas: gas is generated inside the slurry to form a porous, forming a porous calcium phosphate bone cement after curing.

3.在磷酸钙骨水泥骨水泥体系中加入无毒的表面活性剂。 3. Add the surfactant is non-toxic in the calcium phosphate cement in the cement system. 在磷酸钙骨水泥粉末同液体混合后调浆时由于表面张力较小而产生气泡。 When calcium phosphate cement powder with the mixing liquid slurried due to a smaller surface tension bubbles. 气泡均匀分布于浆体中,固化后即形成多孔结构。 Gas bubbles uniformly distributed in the slurry, after cured to form a porous structure.

本发明详细的技术方案如下所述:本发明所说的含有成孔剂的多孔磷酸钙骨水泥主要由磷酸钙骨水泥(CPC)和成孔剂所组成,其比例如下: Aspect of the present invention in detail as follows: The present invention said porous calcium phosphate cement contains pore-forming agent is mainly composed of calcium phosphate cement (CPC) and the porogen composition ratios as follows:

磷酸钙骨水泥∶成孔剂=10∶(0.3~8.7) (重量比)(1)所说的磷酸钙骨水泥(CPC)是由几种磷酸钙盐按一定的比例混合的混合物,可以按(US5525148,US5545254)公开的方法配制,可以是磷酸三钙(α型或β型)、磷酸四钙中的一种或两者的混合物;磷酸八钙、磷酸二氢钙、羟基磷灰石、氟磷灰石中的一种或它们的混合物。 Calcium phosphate cement: porogen = 10 (0.3 to 8.7) (ratio by weight) (1) of said calcium phosphate cement (CPC) is composed of several calcium salts of certain proportions of the mixture may be press (US5525148, US5545254) disclosed formulated, may be tricalcium phosphate ([alpha] type or β type), a mixture of tetracalcium phosphate of one or both; octacalcium phosphate, calcium dihydrogen phosphate, hydroxyapatite, fluorapatite one or mixtures thereof.

(2)所说的成孔剂为无毒的微溶性盐、酸式盐和碱式盐或无毒的表面活性剂中的一种或一种以上,其中:所说的微溶盐可以是在水中微溶的钙盐等,如硫酸钙,碳酸钙,醋酸钙,柠檬酸钙,磷酸氢钙,草酸钙等,以硫酸钙为佳;所说的碱式盐为能在酸性条件下产生CO2的碳酸盐,如碳酸氢钠,碳酸钙等;所说的酸式盐为在水中呈酸性的盐,如磷酸二氢钙,磷酸二氢钾等,碱式盐和酸式盐应等当量加入;所说的表面活性剂为脂肪酸钾盐,脂肪酸钠盐,吐温系列,壬基酚聚氧乙烯醚系列,烷基硫酸钠等,以硬脂酸钾及烷基硫酸钠为佳。 (2) of said pore formers are non-toxic slightly soluble salt, acidic and basic salts or salts of non-toxic surfactants in one or more, wherein: said sparingly soluble salt may be sparingly soluble in water and calcium salts, such as calcium sulfate, calcium carbonate, calcium acetate, calcium citrate, calcium hydrogen phosphate, calcium oxalate, preferably calcium sulfate; salts of said basic under acidic conditions to produce CO2 carbonates, such as sodium bicarbonate, and calcium carbonate; salts of said acidic acid salts, such as calcium dihydrogen phosphate, potassium dihydrogen phosphate in water and the like, basic salts and acid salts and the like should be equiv added; said surfactant is a potassium salt of a fatty acid, fatty acid sodium salt, Tween series, nonylphenol ethoxylates series, like sodium alkyl sulfate, sodium alkyl sulfate and potassium stearate are preferred.

本发明所说的骨水泥是按下述方法进行制备和应用的:(1)将直径小于20μm的磷酸钙骨水泥粉末和直径为200~350μm的微溶盐按磷酸钙骨水泥∶微溶盐=10∶(0.3~8.7)(重量比)的比例混合,即获得含有成孔剂为微溶盐的多孔磷酸钙骨水泥,用生理盐水或其他盐溶液作为固化液,按固液比为3∶1的比例与其混合均匀,即可植入体内;(2)将直径小于20μm的磷酸钙骨水泥与以等当量配置的酸式盐和碱式盐按磷酸钙骨水泥∶微溶盐=10∶(0.3~8 7)(重量比)的比例混合,即获得含有成孔剂为酸式盐和碱式盐的多孔磷酸钙骨水泥,用生理盐水或其他盐溶液作为固化液,按固液比为3∶1的比例与其混合均匀,即可植入体内;(3)以含有0.2%~15%的表面活性剂的水溶液为固化液与直径小于200μm的磷酸钙骨水泥,按固液比为3∶1(重量比)的比例混合均匀,即获得含有成孔剂为表面 Said bone cement of the present invention is prepared and applied as follows: (1) diameter of less than 20μm and calcium phosphate cement powder having a diameter of 200 ~ 350μm sparingly soluble salt The calcium phosphate cement: sparingly soluble salt = 10 (0.3 to 8.7) (weight ratio) mixture, i.e., to obtain a porous calcium phosphate cement contains pore-forming agent is a sparingly soluble salt, or other salt solutions with a physiological saline solution as a curing, by solid-liquid ratio of 3 ratio :1 mixed therewith, can be implanted in vivo; (2) a smaller diameter than the acid and base salts 20μm calcium phosphate cement and arranged by an equivalent amount of calcium phosphate cement: sparingly soluble salt = 10 : (0.3 to 87) (weight ratio) mixture, i.e., to obtain a porous calcium phosphate cement contains pore-forming agent is acid and base salts, and salts with saline or other solution as a curing liquid, solid-press ratio of 3:1 mixed therewith, can be implanted in the body; solution (3) containing 0.2% to 15% surfactant solution with the curing of a diameter less than 200μm phosphate cement, solid-liquid ratio by 3:1 proportion (weight ratio) mixed, i.e. to obtain a surface containing porogen 性剂的多孔磷酸钙骨水泥,即可植入体内。 Porous calcium phosphate bone cement of the agent to the implant body.

(4)将直径小于20μm的磷酸钙骨水泥与以等当量配置的酸式盐和碱式盐、微溶盐以及表面活性剂的水溶液(0.2%~15%)按以下比例混合均匀:磷酸钙骨水泥∶(微溶盐+酸式盐和碱式盐+0.2%~15%的表面活性剂的水溶液)=10∶(0.3~8.7) (重量比)即获得含有成孔剂为酸式盐和碱式盐、微溶盐以及表面活性剂的多孔磷酸钙骨水泥,即可植入体内。 (4) a smaller diameter than the acid and base salts 20μm calcium phosphate cement with an equivalent configuration, a sparingly soluble salt and an aqueous solution of a surfactant (from 0.2% to 15%) uniformly mixed in the following ratio: calcium phosphate cement: (+ sparingly soluble salt aqueous acid salts and base salts +0.2% to 15% of surfactant) = 10 (0.3 - 8.7) (weight ratio) to obtain the acid salt comprising i.e. the porogen is and basic salts, porous calcium phosphate bone cement and sparingly soluble salt surfactants, can be implanted in the body.

发明人对本发明所说的多孔磷酸钙骨水泥进行了模拟体内试验:将上述调制均匀的多孔磷酸钙骨水泥置于37℃和100%湿度的环境中固化2小时,然后再置于模拟体液中浸泡10小时,用体视显微镜观察,表面孔径分布均匀,孔径在100~300μm之间,断面内部有孔径为50~100μm,孔隙率为大,固化体强度好,用扫描电子显微镜观察也可得到相同的结果。 The inventors of the present invention said porous calcium phosphate cement was simulated in vivo test: The above-described modulation uniform porous calcium phosphate cement at 37 ℃ and 100% humidity environment cured for 2 hours, and then placed in a simulated body fluid soak for 10 hours, was observed with a stereomicroscope uniformity, surface pore size distribution, pore size between 100 ~ 300μm, an aperture of the internal section 50 ~ 100μm, large porosity, good strength of the cured body was observed with a scanning electron microscope can be obtained the same results.

因此,本发明所说的多孔硫酸钙骨水泥具有十分显著的优点:不改变磷酸钙骨水泥自行固化的特性,不改变固化后其水化产物主要为羟基磷灰石的成份,水化反应速率基本不变,孔径在100~300μm之间,主要集中在150~250μm之间,有利于骨组织及其它有机组织的长入,加速材料的降解,促进骨的快速愈合,是一种具有广阔应用前景的人体硬组织修复材料。 Accordingly, the present invention said porous calcium sulfate cement has very significant advantages: does not change the calcium phosphate cement self-curing characteristics do not change after curing and the hydration product is predominantly hydroxyapatite composition, the rate of hydration reaction substantially constant pore size between 100 ~ 300μm, mainly between 150 ~ 250μm, and is conducive to bone ingrowth other organic tissue, accelerated degradation of the material to promote rapid bone healing, having a wide application the prospect of human hard tissue repair material.

下面将结合实施例进一步阐明本发明的内容,但这些实施例并不限制本发明的保护范围。 The following examples further illustrate embodiments in conjunction with the present invention, but these examples do not limit the scope of the present invention.

实施例1称取有磷酸氢钙、磷酸四钙和羟基磷灰石组成的粒径小于20μm的粉末3g,称取0.1g 220~350μm硫酸钙加入到粉末中,在研钵中研磨分散均匀,加入1.1g生理盐水,用牙科调制刀调和均匀成泥团,然后放入37℃ 100%湿度环境中固化2小时,然后放入模拟体液中浸泡10小时以上,用体视显微镜检测,表面孔径分布较均匀,在100~200μ之间,断面内部孔径为50~100μm,空隙率较大,固化体强度好,用扫描电子显微镜检测样品断面的孔径大小及分布与体视显微镜的结果一致。 Example 1 There were weighed dicalcium phosphate, tetracalcium phosphate and particle diameter of hydroxyapatite powder is less than 3g 20μm were weighed 0.1g 220 ~ 350μm is added to the calcium sulfate powder, uniformly dispersed in a grinding mortar, 1.1g physiological saline was added, to reconcile even with a dental tool into the clay in the modulation, and then placed in 37 ℃ 100% humidity cured for 2 hours, and then soaked into the simulated body fluid for more than 10 hours with a stereomicroscope detection, surface pore size distribution uniform, between 100 ~ 200μ, pore diameter of interior section 50 ~ 100μm, void ratio is larger, good cured strength, pore distribution with a scanning electron microscope sample cross section consistent with stereomicroscope.

实施例2称取由磷酸氢钙、α-磷酸三钙、磷酸四钙、和羟基磷灰石组成的粉末3g,加入0.3g直径为30~60nm的超细碳酸钙,再加0.7g磷酸二氢钙(Ca(H2PO4)2),在研钵中混合均匀,然后加入2.2g生理盐水,用牙科调制刀调和均匀,然后在37℃和100%湿度的环境中固化24小时,取出,用体视显微镜检查,其孔径的分布在100~200μm,小于100μm较多,孔隙率大。 3g powder taken from the calcium hydrogenphosphate, alpha] tricalcium phosphate, tetracalcium phosphate and hydroxyapatite, said composition of Example 2, was added 0.3g of a diameter of 30 ~ 60nm fine calcium carbonate, dicalcium phosphate plus 0.7g calcium hydroxide (Ca (H2PO4) 2), mixed in a mortar, and then added 2.2g of physiological saline, to reconcile even with a dental modulation knife, and then cured for 24 hours at 37 [deg.] C and 100% humidity environment, taken out, the body stereomicroscope examination, the distribution of pore sizes in the 100 ~ 200μm, less than 100μm more, large porosity.

实施例3称取实施例1中的CPC粉末3g,加入0.3g柠檬酸钙,0.15g粒径为30~60nm的超细碳酸钙和0.35g磷酸二氢钾,加入1.8g 10%(质量比)的壬基酚聚氧乙烯醚的溶液,用调制刀调和均匀,然后在37℃,100%湿度环境中固化24小时,取出,用体视显微镜检查其样品表而孔径分布在100~200μm之间,断面样品分析表明孔径分布在100~200μm之间,固化体强度好,扫描电镜照片也表明孔径基本分布在100~200μm之间,并且孔很深。 Example 3 CPC said powder 3g taken in Example 1 was added 0.3g calcium citrate, 0.15 g of a particle size of 30 ~ 60nm fine calcium carbonate and 0.35g of potassium dihydrogen phosphate was added 1.8g 10% (mass ratio ) solution of polyoxyethylene nonyl phenyl ether, knife reconcile uniform modulation, then at 37 ℃, 100% humidity cured for 24 hours, taken out, check the table for the sample stereomicroscope and pore size distribution of 100 ~ 200μm Room sectional sample analysis showed that the pore size distribution between 100 ~ 200μm, good cured strength, SEM photographs also show pore size distribution substantially between 100 ~ 200μm, and a deep hole.

实施例4称取实施例2中CPC与微溶盐混合的粉末4g,加入1g0.2%硬脂酸钾溶液,用调制刀调和均匀,然后在37℃,100%湿度环境下固化24小时,取出,用体视显微镜观察表面及内部的孔径,表明样品孔径主要分布在200~300μm,样品孔隙率较大。 Example 4 Example CPC weighed mixed with a sparingly soluble salt powder 4g 2, was added 1g0.2% solution of potassium stearate, knife reconcile uniform modulation, then at 37 ℃, cured for 24 hours at 100% humidity, removed, and the internal surface of the pore size of a stereoscopic microscope, the sample showed a pore size distribution mainly in the 200 ~ 300μm, porosity larger sample.

实施例5称取实施例1中CPC粉末3g,加入浓度为15%(重量比)的十二烷基硫酸钠水溶液0.7g,用调制刀调和均匀,然后在37℃,100%湿度环境下固化24小时,取出,用体视显微镜检测样品断面,样品孔隙率大,基本在50~150μm之间,经测定本例的粉末与固化液调和后的凝结时间为6~8min,抗压强度为3-5MPa。 Example 5 Example 1 in said CPC powder 3g embodiment taken, added at a concentration of 15% (by weight) aqueous solution of sodium lauryl sulfate 0.7g, even harmonic modulation knife, then at 37 ℃, 100% humidity cure 24 hours, taken out, the test sample cross-section with a stereomicroscope, a large sample porosity, substantially between 50 ~ 150μm, the setting time was determined according to the present embodiment after the powder and liquid curing reconcile 6 ~ 8min, compressive strength 3 -5MPa.

实施例6制备方法与实施例1相同,加入0.15g草酸钙和浓度为10%的脂肪酸钠水溶液0.8g作为成孔剂,其孔径分布在100~200μm之间,断面样品分析表明孔径分布在50~150μm之间,固化体强度好。 Example 6 prepared in Example 1, was added 0.15g oxalate and fat concentration of 10% aqueous solution of sodium 0.8g as a pore former, the pore size distribution between 100 ~ 200μm, a cross-sectional analysis showed that the pore size distribution in the sample 50 between ~ 150μm, good cured strength.

实施例7制备方法与实施例2相同,采用碳酸氢钠0.3g、磷酸二氢钙0.48g和浓度为1%的(吐温80)水溶液2.1g作为成孔剂,其孔径分布在50~200μm之间,断面样品分析表明孔径分布在50~150μm之间,小于100μm的较多,固化体强度好。 (Tween 80) solution prepared in same manner as in Example 7 and Example 2, using the sodium bicarbonate 0.3g, 0.48g calcium dihydrogen phosphate and 2.1g of 1% concentration as a pore former, the pore size distribution of 50 ~ 200μm between a cross-sectional sample analysis showed that the pore size distribution between 50 ~ 150μm, more of less than 100μm, good cured strength.

实施例8制备方法与实施例1相同,加入0.15g粒径为220~350μm的醋酸钙和浓度为0.5%的(吐温20)的水溶液1g,其孔径分布在50~200μm之间,断面样品分析表明孔径分布在50~150μm之间,固化体强度好。 Example 8 was prepared the same as in Example 1, calcium acetate was added 0.15g particle diameter of 220 ~ 350μm and concentration of 0.5% (Tween 20) an aqueous solution of 1g, pore size distribution between 50 ~ 200μm, the sample section analysis showed that the pore size distribution between 50 ~ 150μm, good cured strength.

实施例9按实施例5将多孔磷酸钙骨水泥粉末同固化液混合,用调制刀调和均匀,在术中填入雄性大鼠颅顶骨全层缺损的一侧,另一侧缺损用普通的非多孔CPC填充,术中固化30min后缝合切口。 Example 9 Example 5 A porous calcium phosphate cement powder was mixed with a curing liquid, homogeneous harmonic modulation knife, side fill parietal defects by male rats during surgery, the other side of the defect by conventional non- CPC porous filler, curing 30min after surgery incision was sutured. 共手术40只大鼠,分2组,于6周和12周取样观察。 40 rats co-operation, divided into 2 groups, 6 weeks and 12 weeks in the sample was observed. 6周时多孔CPC与骨直接愈合,内部可见明显的降解,并伴随软骨细胞的出现,而对照组内部致密,未见成骨。 At 6 weeks of CPC with porous bone healing direct, significant degradation seen inside, accompanied of cartilage cells, and a dense internal control group, no osteogenesis. 12周以后,多孔组内部孔洞较6周时明显增多、增大,并可见大量的软骨细胞出现及矿化骨形成,对照组内部也出现孔洞,但数量少。 After 12 weeks, the internal pores of the porous group significantly increased when compared to 6 weeks, increases, and shows a large number of chondrocytes and mineralized bone formation occurs, the control group also appears inside the holes, but a small number.

标本在计算机内二次成像后,测量各组的孔隙率(每组10个标本,每个标本例5个视野),结果如表:6周(μm2) % 12周(μm2) %普通CPC 2257 3 3763 4多孔CPC 6773 9 11289 15**n=10,P<0.05本实施例表明本发明所说的多孔磷酸钙骨水泥可显著增加材料的降解速率,加速新骨的形成,是一种十分优良的人体硬组织修复材料。 Imaging the specimen after the second computer, porosity is measured in each group (each group of 10 samples, each sample five fields embodiment), the results in Table: 6 weeks (μm2)% 12 circumferential (μm2)% Normal CPC 2257 337634 porous CPC 6773 9 11289 15 ** n = 10, P <0.05 this example demonstrates that the present invention said porous calcium phosphate cement can significantly increase the degradation rate of the material, accelerating the formation of new bone, is a very excellent human hard tissue repair material.

Claims (5)

1.一种含有成孔剂的多孔磷酸钙骨水泥,其特征在于是由常规的磷酸钙骨水泥和成孔剂所组成,所说的成孔剂为微溶性盐、酸式盐和碱式盐或表面活性剂中的一种或一种以上,磷酸钙骨水泥∶成孔剂=10∶(0.3~8.7)重量比;其中:(1)所说的微溶盐为硫酸钙,碳酸钙,醋酸钙,柠檬酸钙,磷酸氢钙,草酸钙中的一种或一种以上;(2)所说的碱式盐为碳酸氢钠、碳酸钙中的一种;所说的酸式盐为磷酸二氢钙、磷酸二氢钾中的一种;碱式盐和酸式盐应等当量加入;(3)所说的表面活性剂为脂肪酸钾盐,脂肪酸钠盐,吐温系列,壬基酚聚氧乙烯醚系列,烷基硫酸钠中的一种或一种以上的水溶液。 A porous calcium phosphate bone cement containing a pore-forming agent, which is characterized by being a conventional calcium phosphate cement and pore forming agent consisting, of said pore forming agent is a sparingly soluble salt, acid salts and base salt or surfactant in one or more calcium phosphate bone cement: porogen = 10 (0.3 to 8.7) by weight ratio; wherein: (1) of said sparingly soluble salt is calcium sulfate, calcium carbonate , calcium acetate, calcium citrate, dibasic calcium phosphate, calcium oxalate of one or more than one; (2) of said basic salt is sodium bicarbonate, a calcium carbonate; and salts of said acid of formula equivalents of basic salt added should be like and acid salts;; monocalcium phosphate is a potassium dihydrogen phosphate (3) of said surfactant is a potassium salt of fatty acid, fatty acid sodium salt, Tween series, nonyl polyoxyethylene phenol series, an aqueous solution of sodium alkyl sulfate of one or more than one.
2.如权利要求1所述的磷酸钙骨水泥,其特征在于:(1)所说的表面活性剂水溶液的浓度为0.2%~15%重量比;(2)所说的微溶盐的粒径为200~350μm。 (2) of said sparingly soluble salt tablets; (1) an aqueous solution of a concentration of said surfactant is from 0.2% to 15% by weight: calcium phosphate cement as claimed in claim 1, characterized in that diameter of 200 ~ 350μm.
3.如权利要求1或2所述的磷酸钙骨水泥,其特征在于所说的微溶盐为硫酸钙。 Or calcium phosphate cement according to claim 12, wherein said sparingly soluble salt is calcium sulfate.
4.如权利要求1或2所述的磷酸钙骨水泥,其特征在于所说的表面活性剂为硬脂酸钾或烷基硫酸钠中的一种。 4. A calcium phosphate bone cement of claim 1 or claim 2, wherein said surfactant alkyl group as a potassium stearate or sodium sulphate.
5.如权利要求1或2所述的磷酸钙骨水泥的应用,其特征在于可作为人体硬组织的修复材料。 5. The use of calcium phosphate cement of claim 1 or claim 2, characterized in that the repair material can be used as human hard tissue.
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