【作者】 李俊；

【导师】 严道南；

【作者基本信息】 南京中医药大学 ， 中医五官科学， 2013， 博士

【摘要】 目的探讨减轻面部整形术后肿胀或加快术后肿胀消退的治疗方法。根据马钱子碱外用治疗肿胀安全有效,将其复合磷脂传递体化后增加其透皮吸收率,成功制备出主药为马钱子优化总生物碱复合磷脂传递体的化瘀消肿凝胶。将此凝胶在小鼠耳致炎肿胀模型上进行抗炎消肿的实验研究,并进行隆鼻术后消肿治疗的临床观察,探讨化瘀消肿凝胶对面部整形术后肿胀的治疗效果,为化瘀消肿凝胶的临床应用提供可靠的实验数据和理论依据。方法1.理论研究阅读中西医学相关文献,整理分析。2.实验研究(1)制备化瘀消肿凝胶：从马钱子总生物碱中去除毒性成分士的宁,提取无毒的、有消肿作用的马钱子优化总生物碱,载入复合磷脂传递体,并制作成凝胶制剂,是为化瘀消肿凝胶。(2)化瘀消肿凝胶抗炎消肿实验：将小鼠右耳涂抹二甲苯致肿,左耳不涂药作为对照造模。对照组给予含20%乙醇的PBS,给药组给予化瘀消肿凝胶,末次给药后用打孔器在左右两耳相同部位打下圆耳片,称重并记录,计算出耳肿胀度和抑肿率。同理,进行了预防给药后造模、末次给药间隔时间、最佳给药剂量等实验。3.临床研究采用随机平行对照的临床试验方法,观察进行假体(膨体或硅胶)隆鼻手术的女性患者病例数120例,共计分为六组：膨体治疗组、硅胶治疗组、膨体对照组、硅胶对照组、膨体空白组、硅胶空白组,每组20例。治疗组的患者从术后即刻予化瘀消肿凝胶外敷(15g/次)至术后第七天,对照组的患者从术后即刻予冰敷(12h/天)至术后第七天,空白组的患者手术区域不予任何处理。所有患者均于术前、术后1天、3天、5天、7天五个时间点分别进行面部三维扫描,通过软件分析得到不同时间点的肿胀厚度、肿胀体积及肿胀度进行比较,从而对药物疗效进行评价。结果1.理论研究结果在分析文献资料的基础上,阐述中医及西医对头面部术后肿胀的认识和治疗方法,提出中药马钱子去毒后可以制成安全有效的化瘀消肿药物,用于治疗面部整形术后肿胀。2.实验研究结果(1)成功制备出主药为马钱子优化总生物碱复合磷脂传递体的化瘀消肿凝胶。(2)化瘀消肿凝胶抗炎消肿实验证明：抗炎实验中,末次给药后20min,剪耳称重,抗炎效果最佳。化瘀消肿凝胶能明显抑制小鼠的耳肿胀,与空白组比较有显著性差异,表明造模成功。化瘀消肿凝胶中马钱子优化总生物碱复合磷脂传递体的有效剂量为30mg·kg-1.其中中剂量组及高剂量组均能显著抵制小鼠的耳肿胀,但没有明显的量效关系。3.临床研究结果假体隆鼻术后使用化瘀消肿凝胶和冰敷均能促进术后肿胀的消退。化瘀消肿凝胶和冰敷相比促进鼻根部消肿效果更明显,具有统计学差异。结论本研究以马钱子为研究对象,基于组分中药思想,将马钱子优化总生物碱载入复合磷脂传递体,并制作成凝胶制剂,命名为化瘀消肿凝胶。将此凝胶用于消肿治疗,通过小鼠模型实验和临床试验证明此化瘀消肿凝胶在抗炎消肿治疗方面具有优越性,提高了经皮给药的生物利用度,促进药物高效率透皮吸收,为马钱子安全应用于术后外敷治疗术后肿胀提供了良好的样板,也是面部整形术后肿胀的一种有效的治疗手段。更多还原

【Abstract】 ObjectiveThis thesis aims to explore the therapeutic methods of reducing facial swelling after plastic surgery or speeding up the fading away of postoperative swelling. Semen strychni is an effective and riskless drug for clinical topical treatment of inflammatory swelling. And the transdermal absorption rate of composite phospholipid transfer body is high. Based on these advantages, we successfully invented a gel preparation named Hua Yu Xiao Zhong Ning Jiao which mainly compose of optimized Semen strychni total alkaloid compound phosphatide transfer body. To investigate the therapeutic effect of Hua Yu Xiao Zhong Ning Jiao on facial swelling after plastic surgery, We take an anti-inflammatory detumescence research on the mouse ear swelling model using the gel preparation. Furthermore, we observe the clinical treatment of the gel preparation on the rhinoplasty. The results provide reliable experimental data and theoretical basis for the clinical application of Hua Yu Xiao Zhong Ning Jiao on facial swelling after plastic surgery.Methods1. Theoretical methods:read traditional Chinese and Western medicine research literatures for analysis and comparison.2. Experimental methods:(1) Producation of the Hua Yu Xiao Zhong Ning Jiao. We make Hua Yu Xiao Zhong Ning Jiao by removing the toxic ingredients strychnine from semen strychni total alkaloid, extracting and purifying repercussive semen strychni optimized total alkaloid with no poison, loading it into composite phospholipid transfer body and conducting it into gel preparation.(2) Anti-inflammatory detumescence research of the Hua Yu Xiao Zhong Ning Jiao. To make a mouse ear swelling model, we daub50μL xylene on the right ear and nothing on the left ear for comparison. PBS containing20%ethanol is givin to the blank control group. Meanwhile, Hua Yu Xiao Zhong Ning Jiao is givin to the treatment group. After the last drug treatment, we weigh and record the same round ear piece from all the ears. The ear swelling degree and inhibitory rate of swelling are calculated based on the weight. Similarly, we carry out experiments on the prevention effect of the gel preparation before molding, the last drug time interval and the identification of the best drug dose.3. Clinical research methods: This study applies random parallel comparison clinic trial method to observe120women who has been carried out rhinoplasty. The120cases are divided into6groups:bulk treatment group, silica gel treatment group, bulk control group, silica gel control group, bulk blank group and silica gel blank group,20cases of each group. Treatment group is provided with the Hua Yu Xiao Zhong Ning Jiao for15g once, which lasted for seven days. Control group is provided with ice for12hours per day, which lasted for seven days. Blank group is provided with nothing. The facial3D scanning, swelling thickness, swelling volume and swelling degree of all groups are recorded respectively at five different time points including the preoperative,1day postoperative,3days postoperative,5days postoperative and7days postoperative. We compared the overall treatment results and evaluated the drug curative effects of the Hua Yu Xiao Zhong Ning Jiao.Results1. Theoretical study results: Based on the analysis of the research literature, we elaborate the thoughts and therapeutic methods of Chinese medicine or Western medicine on facial swelling after plastic surgery. We figure out that the optimized traditional Chinese medicine semen strychni can be used as the main component of the Hua Yu Xiao Zhong Ning Jiao, and can be used in the treatment of facial swelling after plastic surgery.2. The experimental results:(1) Successful preparation of the Hua Yu Xiao Zhong Ning Jiao, which is mainly composed of optimized Semen strychni total alkaloid compound phosphatide transfer body.(2) The anti-inflammatory detumescence experiments demonstrate that best anti-inflammatory time interval of Hua Yu Xiao Zhong Ning Jiao is20minutes after the treatment. The treatment can significantly inhibit mouse ear swelling compared with the blank control group, which demonstrate that the mouse model is successfully established. The effective dose of the Hua Yu Xiao Zhong Ning Jiao is30mg per kg(kilogram). Medium and high dose group could also resist the ear swelling of mice significantly, but there is no clear concentration-response relationship.3. The results of clinical trials:Both the Hua Yu Xiao Zhong Ning Jiao and the ice treatment can promote the fading of swelling on the whole nose after rhinoplasty. However, compared to ice treatment on nasal root swelling, the repercussive effect of Hua Yu Xiao Zhong Ning Jiao is more apparent, with statistical differences.ConclusionThis study focus on a gel preparation named Hua Yu Xiao Zhong Ning Jiao which is made based on the component thoughts of of traditional Chinese medicine. It is made by extracting and purifying optimized semen strychni total alkaloid, being loaded into composite phospholipid transfer body and joined into a gel preparation. Through the mouse model experiments and clinical trials, we proved that the gel preparation has remarkable repercussive and anti-inflammatory effect on plastic surgery swelling. Also, it reveals that Hua Yu Xiao Zhong Ning Jiao enhances percutaneous drug bioavailability and promotes drug absorption through skin. Moreover, the study provides a good model for the application safety of semen strychni on extermal treatment after surgery swelling. It also provides an effective therapeutic method for the facial plastic surgery swelling.更多还原