复合唑来膦酸骨水泥的制备和可行性研究

发布时间：2018-02-28 05:51

本文关键词： 骨水泥唑来膦酸生物力学药释特性　出处：《泰山医学院》2012年硕士论文　论文类型：学位论文

【摘要】：目的骨巨细胞瘤（Giant cell tumor of bone，GCT）是一种常见的原发性骨肿瘤，约占所有原发骨肿瘤的4-5%，良性骨肿瘤的15%，东西方国家的发病率不同，东方国家发病率明显高于西方国家，女性发病率高于男性。其特点为潜在恶性和侵袭性,而且局部复发率高。临床上为解决其高复发率，主要采用切刮术后骨水泥填塞、电刀灼烧瘤壁、高速磨钻打磨骨嵴以及无水乙醇浸泡瘤腔、液氮冷冻等辅助措施。但具体哪一种辅助措施能明显的降低其局部复发率，目前尚无定论。二磷酸盐类药物是一种人工合成的焦磷酸盐类似物，是目前临床上最为重要的一组治疗由破骨细胞介导以骨吸收为特点的疾病的药物。被广泛应用于各种恶性肿瘤的骨转移、恶性肿瘤引起的高钙血症、骨质疏松症、佩吉特骨病等疾病。最近的研究表明二磷酸盐治疗骨巨细胞瘤可降低其复发率。二磷酸盐的给药方式主要是口服和静脉给药。存在生物利用度低、用药时间长、治疗费用昂贵和上消化道溃疡等不良反应。局部给药是一种理想的选择。唑来膦酸是第三代二磷酸盐类药物的代表药，具有应用剂量小、疗效高等优点，骨水泥是多种药物的良好载体。复合唑来膦酸骨水泥的安全性和有效性需通过骨水泥的生物力学检测、药物载体系统的洗提特性研究来证实。本文就通过上述方面的研究初步评价复合唑来膦酸骨水泥的可行性。为临床应用复合二磷酸盐骨水泥治疗骨巨细胞瘤奠定生物力学和体外药动学基础。方法 1复合唑来膦酸骨水泥的制备和生物力学研究在40g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑来膦酸纯粉。制备骨水泥压缩、抗弯强度和模量实验标本。用深圳瑞格尔RGT-10A型微机力学试验机测定各组骨水泥浸提前和浸提4W后的抗压强度、抗弯强度和模量。抗弯强度和模量应用四点弯曲实验测定。 2浸提实验研究 2.1实验方案一在40g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑来膦酸制备浸提标本，每组1个标本放在50ml生理盐水中，，在37℃恒温箱里浸提4周，在1、2、3、4、5、6、7、9、11、14、17、21、28d取样品2.5ml，用高效液相色谱仪测定唑来膦酸的浓度，计算各时点的释放速率和释放总量百分比。 2.2实验方案二在1.0g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑来膦酸制备浸提标本，每组1个标本放在5ml生理盐水中，在37℃恒温箱里浸提4周，在1、2、3、4、5、6、7、9、11、14、17、21、28d取样品2.5ml，用高效液相色谱仪测定唑来膦酸的浓度，计算各时点的释放速率和释放总量百分比。 2.3实验方案三更换骨水泥品牌后，在1.0g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑来膦酸制备浸提标本，每组1个标本放在5ml生理盐水中，在37℃恒温箱里浸提4周，在1、2、3、4、5、6、7、9、11、14、17、21、28d取样品2.5ml，用高效液相色谱仪测定唑来膦酸的浓度，计算各时点的释放速率和释放总量百分比。结果 1在40g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑来膦酸。对浸提前和浸提4w后骨水泥的抗压强度有显著影响，对骨水泥抗弯模量和抗弯强度无明显影响。浸提前和浸提后的抗压强度、抗弯模量和强度均符合ISO5833-2002骨水泥行业标准。 2在各套实验方案中，样品溶液中均未能检测到唑来膦酸。结论 1各组骨水泥浸提前和浸提4周后的静态机械性能均符合骨水泥ISO5833(2002)标准。在40g骨水泥粉末中加入4mg唑来膦酸不会降低浸提前和浸提4W后的抗压强度（CSR）、抗弯强度（BSR）和模量（BMR）。 2骨水泥粉体中直接添加唑来膦酸并以手工方法混合制备复合唑来膦酸骨水泥不可行。
[Abstract]:objective
Giant cell tumor of bone (Giant cell tumor of bone, GCT) is one of the most common primary bone tumors, accounting for about 4-5% of all primary bone tumors, 15% benign bone tumors, the incidence rate of different eastern and Western countries, Eastern countries incidence was significantly higher than that in western countries, women with high incidence in the male. The characteristics for potential malignant and invasive, and high local recurrence rate in clinic. In order to solve the high recurrence rate, mainly by curettage after bone cement filling, electric knife burn aneurysm wall. High speed drill grinding bone ridge and ethanol tumor cavity, frozen in liquid nitrogen and other auxiliary measures. But what kind of specific the auxiliary measures can significantly reduce the local recurrence rate, there is no conclusion. Two phosphate drug is a synthetic analogue of pyrophosphate, is currently the most clinically important treatment group by osteoclast mediated bone resorption by drugs for the characteristics of the disease. Widely used in a variety of malignant tumor bone metastasis, malignant hypercalcemia caused by cancer, osteoporosis, bone disease and Paget disease. Recent studies show that two of phosphate treatment of giant cell tumor of bone can reduce the recurrence rate of two. The phosphate administration is the main way of oral and intravenous administration. There is low bioavailability, medication for a long time the adverse reactions, the treatment is expensive and peptic ulcer. The local delivery is an ideal choice. Zoledronic acid is a representative drug of third generation two phosphate drugs, with the application of small dosage, high curative effect, the bone cement is a good carrier of multiple drugs. Clinical efficacy and safety of compound of phosphonic acid bone cement to bone cement by biomechanical testing, study the elution characteristics of drug delivery system to confirm. This paper through the research of the preliminary evaluation of zoledronic acid composite bone cement can be It lays the foundation of biomechanics and in vitro pharmacokinetics for the clinical application of compound two phosphate bone cement in the treatment of giant cell tumor of bone.
Method
Study on the preparation and biomechanical study of 1 compound zoledronic acid bone cement
Join the 0mg, in the 40g bone cement powder in 0.5mg, 1mg, 2mg, 4mg zoledronic acid pure powder. Preparation of bone cement compression, bending strength and modulus of the specimens were measured. The compressive strength of bone cement leaching and leaching in advance after 4W mechanical Shenzhen ruigeer RGT-10A microcomputer testing machine, bending the strength and modulus. Determination of flexural strength and modulus by four point bending test.
Experimental study on 2 extraction
2.1 experimental scheme 1
Join the 0mg, in the 40g bone cement powder in 0.5mg, 1mg, 2mg, 4mg zoledronic acid preparation extraction specimens, 1 specimens of each group in 50ml normal saline, 37 degrees in the incubator to extract for 4 weeks, 1,2,3,4,5,6,7,9,11,14,17,21,28d in the 2.5ml samples, using HPLC to determine the concentration of zoledronic acid, calculation of the release rate of each point and the total release percentage.
2.2 experimental scheme two
Join the 0mg, in the 1.0g bone cement powder in 0.5mg, 1mg, 2mg, 4mg zoledronic acid preparation extraction specimens, 1 specimens of each group in 5ml normal saline, 37 degrees in the incubator to extract for 4 weeks, 1,2,3,4,5,6,7,9,11,14,17,21,28d in the 2.5ml samples, using HPLC to determine the concentration of zoledronic acid, calculation of the release rate of each point and the total release percentage.
2.3 experimental scheme three
The replacement of bone cement brand after joining the 0mg, in the 1.0g bone cement powder in 0.5mg, 1mg, 2mg, 4mg zoledronic acid preparation extraction specimens, 1 specimens of each group in 5ml normal saline, 37 degrees in the incubator to extract for 4 weeks in 1,2,3,4,5,6,7,9,11,14,17,21,28d 2.5ml samples with high performance liquid. Chromatography determination of zoledronic acid, calculation of the release rate of each point and the total release percentage.
In 1 40g bone cement powder with 0mg, 0.5mg, 1mg, 2mg, 4mg. Zoledronic acid has a significant influence on the compressive strength of bone cement leaching in advance and extraction of 4W, had no effect on bone cement flexural modulus and flexural strength and compressive strength. Early leaching leaching Tim, resistance the bending modulus and strength are in line with ISO5833-2002 bone cement industry standards.
2 in the set of experimental schemes, zoledronic acid was not detected in the sample solution.
1, the static mechanical properties of each group after bone cement leaching in advance and 4 weeks after extraction were all in line with bone cement ISO5833 (2002) standard. Adding 4mg zoledronic acid into 40g bone cement powder did not reduce the compressive strength (CSR), bending strength (BSR) and modulus (BMR) of 4W after leaching and extraction.
It is not feasible to prepare zoledronic acid cement by direct addition of zoledronic acid in 2 bone cement powder by hand method.

【学位授予单位】：泰山医学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R738.1;R318.08

【参考文献】