西甲硅油论文：西甲硅油挥发性物质、消泡力和含量测定研究

西甲硅油论文：西甲硅油挥发性物质、消泡力和含量测定研究【中文摘要】西甲硅油是聚二甲基硅氧烷和4%-7%二氧化硅的复合物,具有低的表面张力和较好的生物学及化学稳定性。

本品由德国柏林一化学股份公司在上世纪七十年代开发上市,在欧美等国家地区已使用了三十多年。

自2001年我国卫生部允许进口德国Berlin-Chemie AG生产的西甲硅油乳剂(商品名：艾普米森、柏西)以来,该药物已经大范围应用于临床。

西甲硅油在临床上主要用于因气体在腹部聚集而引起的胃肠道不适,如暖气、术后腹胀等,还可用于治疗功能性消化不良、肠易激综合症、术后肠梗阻,以及腹部影像学检查的辅助用药(如X射线、超声胃镜)和作为造影剂的添加剂。

USP-34版和BP2011年版均收载有西甲硅油及其制剂。

美英药典对西甲硅油挥发性物质的测定,仅为总量测定,无挥发性物质各组分结构的确认和含量测定；对西甲硅油及其制剂消泡力的检查均为定性检查,无消泡力的定量检查方法。

中国药典从未收载过西甲硅油,只收载有二甲硅油及其片剂和气雾剂,亦无挥发性物质组分测定及二甲硅油消泡力检查项。

因此,积极组织力量研究西甲硅油挥发性物质各组分结构和含量、建立简便易行的消泡力定量检查方法以及采用红外光谱法测定其新制剂中西甲硅油含量,这对于西甲硅油及其制剂的质量控制、毒副作用的临床监测、医生及患者的合理选药用药等,具有十分重要的理论意义和现实意义。

第一部分,气相色谱-质谱法研究西甲硅油挥发性物质的组成。

采用气相色谱-质谱联用仪测定西甲硅油的挥发性物质,并对其组分进行了定性定量分析。

通过质谱图解析和谱峰的规律性研究,对粘度为500cst的西甲硅油中挥发性物质的组成进行定性分析；根据GC谱图,采用峰面积归一化法对各组分进行定量分析；加热失重法测定西甲硅油中挥发性物质的总含量。

分析共确定了样品中的42个组分,占挥发性物质总量的99.21%,包括两组同系物：20种链状甲基聚硅氧烷(MDmM, MM到MD21M)和22种环状甲基聚硅氧烷(Dn,D3到D24),研究结果为改进西甲硅油的生产工艺和控制西甲硅油的质量提供了科学依据。

第二部分,西甲硅油与二甲硅油消泡性能对比研究。

测定并比较西甲硅油和二甲硅油的消泡性能,为临床合理选药提供依据。

采用自建的量筒法测定加入分散剂前后西甲硅油和二甲硅油的消泡性能,西甲硅油的相关组分——不同粘度的二甲硅油、二氧化硅以及不同含量二氧化硅的西甲硅油的消泡性能；分别用量筒法、振荡摇瓶法、通气鼓泡法、罗氏泡沫法比较西甲硅油和二甲硅油的消泡性能。

结果西甲硅油和二甲硅油经叔丁醇或丁酮分散处理后,其消泡力及抑泡力均显著优于单纯的西甲硅油和二甲硅油(P<0.05)；粘度为500mm2·s-1的二甲硅油的消泡性能优于其他粘度的二甲硅油(P<0.05);单纯的二氧化硅消泡性能弱；含5%二氧化硅的西甲硅油消泡性能最优(P<0.05)；量筒法测定西甲硅油的消泡力和抑泡力分别是二甲硅油的9.2倍和1.6倍；振荡摇瓶法测定西甲硅油的消泡力和抑泡力分别是二甲硅油的12.2倍和1.3倍；通气鼓泡法和罗氏泡沫法测定西甲硅油的消泡性能都优于二甲硅油。

说明西甲硅油的消泡性能优于二甲硅油,其消泡力是二甲硅油的10倍左右。

第三部分,红外光谱法测定复方枸橼酸阿尔维林软胶囊中西甲硅油的含量。

选用正己烷萃取西甲硅油,根据聚二甲基硅氧烷在1260cm-1波数处Si-CH3基团的对称变形振动有特征吸收峰,使用红外光谱波数为1330cm-1～1180cm-1,分辨率：2.0 cm-1,狭缝：宽,响应：快；温度：25℃；相对湿度：50%。

在选定的分析条件下,系统适用性、精密度和稳定性良好；西甲硅油在1.0 mg·mL-1～24.0 mg·mL-1浓度范围内呈良好线性关系(r=0.9965)；加样回收率为100.79%(RSD=1.68%,n=9)；三批样品含量测定结果分别为标示量的98.70%、97.93%、98.58%。

该方法简便快速,专属性强,精密度高,适用于复方枸橼酸阿尔维林软胶囊中西甲硅油的含量测定。

【英文摘要】Simethicone is a mixture of polydimethylsiloxane (PDMS) and silicon dioxide, with lower surface tension, better biological and chemical stability. This product was developed in the 70s of the last century by the German Berlin-Chemie AG. It has been used for more than 30 years in Europe, the United States, and other regions. Simethicone emulsion has been used extensively in clinical at home since Chinese Ministry of Health allowed to importsimethicone emulsion which is produced by German Berlin-Chemie AG. Simethicone is mainly used for treating gastrointestinal complaints caused by gas accumulation in the abdomen in clinical, such as belching, flatulence, and postoperative abdominal distention, etc. It also can be used for treating functional dyspepsia, irritable bowel syndrome, postoperative ileus, and adjuvant of abdominal imaging examinations. It is also reported that simethicone is used as an adjunct to contrast media suspensions.The USP-34 and BP 2011 edition both contained simethicone and its preparations. But the USP and BP just determined the total content of the volatile matter of simethicone, the structure and content of every component was not determined. And they only determined the defoaming properties of simethicone and its preparations qualitatively, did not have a quantitative method. The Ch.P has never contained simethicone, but dimethicone and its tablet and aerosol, it also did not contain structure analysis of volatile matter and the check item of defoaming properties. Consequently, it has very important theoretical and practical significance to study the structure and content of volatile matter, establish a quantitative method for checking defoaming properties,determine the content of simethicone in new preparations by IR, for the quality control of simethicone and its preparations, monitoring of drug side effects in clinical, rational drug selection of doctors and the ponents analysis of volatile matter in simethicone by Gas Chromatography- Mass Spectrometry. We established a method to analysis components of volatile matter in simethicone API qualitatively and quantitatively. The qualitative analysis of components of volatile matter in simethicone with the viscosity of 500cst was studied using GC-MS, through the interpretation of the mass spectrogram and investigation of the law of peaks; Area normalization method was used for preliminary quantitative analysis according to GC spectrogram. In conclusion,42 components were identified, which accounted for over 99.21%of the total volatile matter, included two sets of homologous compound:20 species of linear Methylpolysiloxane (MDmM, MM to MD21M) and 22 species of cyclic Methylpolysiloxane (Dn, D3to D24). The results are guiding significance on improving the product process of polydimethylsiloxane and investigating the quality control of simethicone parative study on the defoaming properties of simethicone and dimeticone.The defoaming properties of simethicone and dimeticone was measured and compared, to provide a basis for rational drug selection in clinical. The defoaming properties of simethicone and dimeticone before and after adding the dispersant were measured by the self-builted cylinder method. The relevant different contents of silica were determined. The defoaming properties of simethicone and dimeticone were compared through the cylinder method, shake-flask method, bubbling method and roche bubble method. The defoaming properties of simethicone and dimeticone added the dispersant that was tertiary butyl alcohol or methyl ethyl ketone were better than the pure simethicone and dimeticone (P<0.05). The defoaming properties of dimeticone whose kinematic viscosity was 500mm2·s-1 were better than other dimeticone (P<0.05). Single silica had weak defoaming properties. The defoaming properties of simeticone with 5% silica were best (P<0.05). The defoaming activity and foaming suppression of simethicone were 9.2 times,1.6 times than that of dimeticone through the cylinder method. The defoaming activity and foaming suppression of simethicone were 12.2 times,1.3 times than that of dimeticone through the Shake-flask method. The defoaming properties of simethiconewere better than that of dimeticone through bubbling method and roche bubble method. In conclusion, the defoaming properties of simethicone are better than that of dimeticone, the defoaming activity of simethicone is about 10 times than that of dimeticone.Determination of simethicone in Compound Alverine Citrate Soft Capsules by IR. An infrared spectroscopy method was establised to determine simethicone in Compound Alverine Citrate Soft Capsules. Simethicone in the drug was extracted by N-hexane to assay quantitatively, on the basis of the characteristic absorption peak of polydimethylsiloxane in 1260cm-1 wave number of Si-CH3 group’s symmetric deformation vibration. The determined IR wave number range was 1330cm-1 to 1180cm-1; The resolution was 2.0 cm-1; The choosed slit was wide, and the response speed was fast. The setting temperature was 25℃, RH was 50%. On the selective analytic condition, the linear range was 1.0 mg-mL-1-24.0 mg-mL-1 (r=0.9965) and the average recovery (n=9) was 100.79% with RSD 1.68%. The system suitability, precision and stability were fine. The content test results of three batchs sample products were 98.70%,97.93% and 98.58% of the labelled. The method is simple, tachy, accurate and specific. It can be used to assay simethicone inCompound Alverine Citrate Soft Capsules.【关键词】西甲硅油二甲硅油挥发性物质消泡力含量测定【英文关键词】Simethicone Dimethicone Volatile Matter Defoaming Activity Determination 【目录】西甲硅油挥发性物质、消泡力和含量测定研究主要英文缩写一览表7-8摘要8-10Abstract10-12第1章文献综述13-25 1.1 西甲硅油简介13 1.2 西甲硅油作用机制13 1.3 西甲硅油临床应用13-19 1.3.1 腹胀13-15 1.3.2 胃肠道镜检前的准备15-17 1.3.3 肠易激综合征17 1.3.4 功能性消化不良17-18 1.3.5 肠梗阻18 1.3.6 肝硬化18-19 1.3.7 婴儿呕吐、腹胀等19 1.4 甲硅油的合成方法19-20 1.4.1 西甲硅油的制备19 1.4.2 二甲硅油的合成19-20 1.5 西甲硅油的质量标准研究概况20-25 1.5.1 英国药典和美国药典中西甲硅油标准内容比较20-23 1.5.2 消泡能力测定方法23-24 1.5.3 含量测定24-25第2章引言25-27第3章气相色谱-质谱法研究西甲硅油挥发性物质的组成27-41 3.1 材料27-28 3.1.1 仪器27 3.1.2 试剂27-28 3.2 方法28 3.2.1 西甲硅油挥发性物质总含量测定28 3.2.2 西甲硅油挥发性物质组成的测定28 3.3 结果28-38 3.3.1 挥发性物质总含量28-29 3.3.2 西甲硅油对照品及样品的总离子流图29 3.3.3 西甲硅油挥发性物质质谱图29-33 3.3.4 西甲硅油挥发性物质较低分子量组分保留时间与结构单元数目的关系33 3.3.5 GC-MS定性定量分析结果33-38 3.4 讨论38-41 3.4.1 挥发性物质各组分的质谱特征38-39 3.4.2 挥发性物质中较高分子量组分的定性分析39 3.4.3 关于D4和MM的含量39 3.4.4 关于PDMS的合成工艺39-41第4章西甲硅油与二甲硅油消泡性能对比研究41-53 4.1 材料41 4.1.1 仪器41 4.1.2 试药41 4.2 方法与结果41-51 4.2.1 西甲硅油原料药消泡力检查方法的建立41-44 4.2.2 消泡力检查方法验证44 4.2.3 量筒法测定药品的消泡性能44-45 4.2.4 供试品处理方法的选择45-46 4.2.5 西甲硅油相关组分消泡性能实验46-48 4.2.6 西甲硅油与二甲硅油消泡性能对比实验48-51 4.3 讨论51-53第5章红外光谱法测定复方枸橼酸阿尔维林软胶囊中西甲硅油的含量53-59 5.1 材料53-54 5.1.1 仪器53-54 5.1.2 试药54 5.2 方法与结果54-57 5.2.1 测定条件和方法54 5.2.2 溶液的制备54-55 5.2.3 系统适用性试验55-56 5.2.4 线性关系考察56 5.2.5 重复性试验56 5.2.6 加样回收率56-57 5.2.7 稳定性试验57 5.2.8 样品含量测定57 5.3 讨论57-59参考文献59-65致谢65-67在校期间发表论文和参加科研情况67-68。