本文關(guān)鍵詞： 骨水泥 唑來膦酸 生物力學(xué) 藥釋特性　出處：《泰山醫(yī)學(xué)院》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：目的 骨巨細(xì)胞瘤（Giant cell tumor of bone，GCT）是一種常見的原發(fā)性骨腫瘤，約占所有原發(fā)骨腫瘤的4-5%，良性骨腫瘤的15%，東西方國家的發(fā)病率不同，東方國家發(fā)病率明顯高于西方國家，女性發(fā)病率高于男性。其特點(diǎn)為潛在惡性和侵襲性,而且局部復(fù)發(fā)率高。臨床上為解決其高復(fù)發(fā)率，主要采用切刮術(shù)后骨水泥填塞、電刀灼燒瘤壁、高速磨鉆打磨骨嵴以及無水乙醇浸泡瘤腔、液氮冷凍等輔助措施。但具體哪一種輔助措施能明顯的降低其局部復(fù)發(fā)率，目前尚無定論。二磷酸鹽類藥物是一種人工合成的焦磷酸鹽類似物，是目前臨床上最為重要的一組治療由破骨細(xì)胞介導(dǎo)以骨吸收為特點(diǎn)的疾病的藥物。被廣泛應(yīng)用于各種惡性腫瘤的骨轉(zhuǎn)移、惡性腫瘤引起的高鈣血癥、骨質(zhì)疏松癥、佩吉特骨病等疾病。最近的研究表明二磷酸鹽治療骨巨細(xì)胞瘤可降低其復(fù)發(fā)率。二磷酸鹽的給藥方式主要是口服和靜脈給藥。存在生物利用度低、用藥時(shí)間長、治療費(fèi)用昂貴和上消化道潰瘍等不良反應(yīng)。局部給藥是一種理想的選擇。唑來膦酸是第三代二磷酸鹽類藥物的代表藥，具有應(yīng)用劑量小、療效高等優(yōu)點(diǎn)，骨水泥是多種藥物的良好載體。復(fù)合唑來膦酸骨水泥的安全性和有效性需通過骨水泥的生物力學(xué)檢測、藥物載體系統(tǒng)的洗提特性研究來證實(shí)。本文就通過上述方面的研究初步評價(jià)復(fù)合唑來膦酸骨水泥的可行性。為臨床應(yīng)用復(fù)合二磷酸鹽骨水泥治療骨巨細(xì)胞瘤奠定生物力學(xué)和體外藥動(dòng)學(xué)基礎(chǔ)。 方法 1復(fù)合唑來膦酸骨水泥的制備和生物力學(xué)研究 在40g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑來膦酸純粉。制備骨水泥壓縮、抗彎強(qiáng)度和模量實(shí)驗(yàn)標(biāo)本。用深圳瑞格爾RGT-10A型微機(jī)力學(xué)試驗(yàn)機(jī)測定各組骨水泥浸提前和浸提4W后的抗壓強(qiáng)度、抗彎強(qiáng)度和模量�？箯潖�(qiáng)度和模量應(yīng)用四點(diǎn)彎曲實(shí)驗(yàn)測定。 2浸提實(shí)驗(yàn)研究 2.1實(shí)驗(yàn)方案一 在40g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑來膦酸制備浸提標(biāo)本，每組1個(gè)標(biāo)本放在50ml生理鹽水中，，在37℃恒溫箱里浸提4周，在1、2、3、4、5、6、7、9、11、14、17、21、28d取樣品2.5ml，用高效液相色譜儀測定唑來膦酸的濃度，計(jì)算各時(shí)點(diǎn)的釋放速率和釋放總量百分比。 2.2實(shí)驗(yàn)方案二 在1.0g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑來膦酸制備浸提標(biāo)本，每組1個(gè)標(biāo)本放在5ml生理鹽水中，在37℃恒溫箱里浸提4周，在1、2、3、4、5、6、7、9、11、14、17、21、28d取樣品2.5ml，用高效液相色譜儀測定唑來膦酸的濃度，計(jì)算各時(shí)點(diǎn)的釋放速率和釋放總量百分比。 2.3實(shí)驗(yàn)方案三 更換骨水泥品牌后，在1.0g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑來膦酸制備浸提標(biāo)本，每組1個(gè)標(biāo)本放在5ml生理鹽水中，在37℃恒溫箱里浸提4周，在1、2、3、4、5、6、7、9、11、14、17、21、28d取樣品2.5ml，用高效液相色譜儀測定唑來膦酸的濃度，計(jì)算各時(shí)點(diǎn)的釋放速率和釋放總量百分比。結(jié)果 1在40g骨水泥粉末中加入0mg、0.5mg、1mg、2mg、4mg唑來膦酸。對浸提前和浸提4w后骨水泥的抗壓強(qiáng)度有顯著影響，對骨水泥抗彎模量和抗彎強(qiáng)度無明顯影響。浸提前和浸提后的抗壓強(qiáng)度、抗彎模量和強(qiáng)度均符合ISO5833-2002骨水泥行業(yè)標(biāo)準(zhǔn)。 2在各套實(shí)驗(yàn)方案中，樣品溶液中均未能檢測到唑來膦酸。結(jié)論 1各組骨水泥浸提前和浸提4周后的靜態(tài)機(jī)械性能均符合骨水泥ISO5833(2002)標(biāo)準(zhǔn)。在40g骨水泥粉末中加入4mg唑來膦酸不會(huì)降低浸提前和浸提4W后的抗壓強(qiáng)度（CSR）、抗彎強(qiáng)度（BSR）和模量（BMR）。 2骨水泥粉體中直接添加唑來膦酸并以手工方法混合制備復(fù)合唑來膦酸骨水泥不可行。
[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.

【學(xué)位授予單位】：泰山醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R738.1;R318.08

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 牛曉輝;骨巨細(xì)胞瘤的診斷與治療[J];癌癥進(jìn)展;2005年04期

2 楊宣濤,張賢良,步宏,成娘,陳代云;血管內(nèi)皮生長因子受體在骨巨細(xì)胞瘤中的表達(dá)及其與腫瘤增殖和血管生成關(guān)系的研究[J];中國骨腫瘤骨病;2003年01期

3 林建華,張文明,戴伯川,吳芳;阿霉素—磷酸鈣骨水泥緩釋體系的制備及體外藥物釋放試驗(yàn)[J];中國骨腫瘤骨病;2003年04期

4 龔海洋;蔡鄭東;;二膦酸鹽用于腫瘤治療的研究進(jìn)展[J];醫(yī)學(xué)研究生學(xué)報(bào);2008年07期

5 孫強(qiáng);鄭加法;劉德南;;聚甲基丙烯酸甲酯骨水泥作為抗腫瘤藥物緩釋載體的實(shí)驗(yàn)研究[J];中華腫瘤防治雜志;2010年11期

6 劉治;宋德業(yè);;復(fù)合阿倫磷酸鈉骨水泥洗提特性的實(shí)驗(yàn)研究[J];中國現(xiàn)代手術(shù)學(xué)雜志;2011年02期

7 應(yīng)明;二磷酸鹽類藥物[J];江蘇醫(yī)藥;1999年07期

8 范衛(wèi)民,馬益民,王青;二磷酸鹽對人工關(guān)節(jié)松動(dòng)影響的實(shí)驗(yàn)研究[J];江蘇醫(yī)藥;2000年08期

9 鄭國鋼,方瀅芝;高效液相色譜法測定注射用唑來膦酸的含量[J];藥學(xué)實(shí)踐雜志;2003年06期

10 張威;甄健存;邢穎;馬子靜;;載抗生素骨水泥的研究進(jìn)展[J];中國藥房;2006年20期

本文編號：1546036