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甲氨蝶呤緩釋植入劑對(duì)S180肉瘤小鼠的藥效學(xué)研究

發(fā)布時(shí)間:2018-01-19 08:46

  本文關(guān)鍵詞: 癌癥 甲氨蝶呤緩釋植入劑 復(fù)發(fā) 肉瘤 抑瘤率 出處:《合肥工業(yè)大學(xué)》2017年碩士論文 論文類型:學(xué)位論文


【摘要】:目的:制備甲氨蝶呤緩釋植入劑,檢測其體外降解度,以及體外、內(nèi)釋放度。研究其延遲小鼠肉瘤局部復(fù)發(fā)的作用以及對(duì)s180肉瘤藥效學(xué)研究,探討與傳統(tǒng)給藥方式相比其優(yōu)勢(shì)。方法:1)以PLGA和PEG4000為輔料,采用熔融擠出法制備甲氨蝶呤緩釋植入劑。采用紫外光度法和高效液相色譜法分別檢測其體外、內(nèi)釋放度以及真實(shí)含藥量。2)于昆明小白鼠腋下皮下注射Sarcoma 180細(xì)胞,模擬術(shù)后殘留病灶,建立肉瘤術(shù)后輔助化療模型,對(duì)甲氨蝶呤緩釋植入劑延遲肉瘤復(fù)發(fā)作用做出評(píng)價(jià)。3)于昆明小白鼠腋下皮下注射Sarcoma 180細(xì)胞,建立S180肉瘤模型,對(duì)甲氨蝶呤緩釋植入劑抑制腫瘤生長做出評(píng)價(jià)。結(jié)果:甲氨蝶呤緩釋植入劑實(shí)際含藥量為8.34%±0.65,實(shí)際含量與理論含量呈一致性,在體外、內(nèi)可分別達(dá)到7 d和15 d的長效釋放。同劑量下,與注射液組相比,生存期中位數(shù)明顯在增加,且甲氨蝶呤緩釋植入劑抑瘤率高達(dá)77.06%,而甲氨蝶呤注射液抑瘤率僅30.15%。結(jié)論:甲氨蝶呤緩釋植入劑可達(dá)到緩釋藥物的效果,與傳統(tǒng)給藥方式相比甲氨蝶呤緩釋植入劑能更有效地延遲腫瘤復(fù)發(fā)且抑制腫瘤生長,同時(shí)延長了小鼠的生存期。
[Abstract]:Objective: to prepare a sustained-release methotrexate implant and to detect its degradation in vitro and its release in vitro and to study the role of MTX in delaying the local recurrence of sarcoma in mice and its pharmacodynamic study on S180 sarcoma. To explore the advantages of traditional drug administration method: 1) PLGA and PEG4000 were used as adjuncts. Methotrexate sustained-release implants were prepared by melt extrusion method. UV spectrophotometry and high performance liquid chromatography (HPLC) were used to detect methotrexate in vitro. Sarcoma 180 cells were injected subcutaneously into Kunming mice subaxillary to simulate the residual lesions and to establish the model of adjuvant chemotherapy after sarcoma operation. To evaluate the delayed recurrence effect of methotrexate (MTX) implants. 3) to establish S180 sarcoma model by subaxillary injection of Sarcoma 180 cells in Kunming mice. Results: the actual content of methotrexate sustained-release implants was 8.34% 鹵0.65, which was consistent with the theoretical content in vitro. The median survival time was significantly higher than that in the injection group, and the tumor inhibition rate of MTX was as high as 77.06%. The inhibition rate of methotrexate injection was only 30.15. Conclusion: methotrexate sustained-release implant can achieve the effect of sustained-release drug. Compared with traditional administration methotrexate sustained-release implants can delay tumor recurrence and inhibit tumor growth and prolong survival time of mice.
【學(xué)位授予單位】:合肥工業(yè)大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R965

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