猪去氧胆酸与鹅去氧胆酸的提取纯化工艺

从提取胆红素后的猪胆粉中同时提取猪去氧胆酸与鹅去氧胆酸。将猪胆粉皂化制得混合猪胆汁酸粗品,在浓盐酸催化下形成甲酯,猪去氧胆酸甲酯与甲苯形成的复合物不溶于甲苯而结晶析出,蒸干回收溶剂;用柱层析法,以乙酸乙酯一石油醚为洗脱剂分离鹅去氧胆酸甲酯;最后经碱水解得到纯猪去氧胆酸与鹅去氧胆酸,纯度经HPLC测定均大于98％。该提取工艺能同时提取出猪胆粉中的猪去氧胆酸与鹅去氧胆酸,步骤少、操作简单、原料利用充分。适合于工业化生产。     

鹅去胆酸提取分离

提取胆红素后的废弃物在碱液中水解、酸化得到混合猪胆酸粗品,然后经过甲酯化,乙酰化反应,重结晶得到鹅去氧胆酸甲酯二乙酸酯,最后在碱液条件下水解、酸化得到鹅去氧胆酸。每一批料提取后的剩余物经水解后可以重复使用,不影响新加入的物料的提取操作,提高了收率,可使总收率提高到20%,而且提取过程中不需要使用有毒的苯。     

猪去氧胆酸的波谱学研究

通过NMR(1H,13C,DEPT,1H1-H COSY,HSQC,HMBC)及MS测试,对猪去氧胆酸的结构进行了详细地表征。对其H和C进行了完全地归属,并根据MS的相关碎片峰,提出了其可能的裂解途径机理。通过波谱学研究,使得猪去氧胆酸的结构确证更加地完整详尽。     

奥贝胆酸关键异构体杂质的合成研究

以(Z)-6-亚乙基-鹅去氧胆酸为原料,经氢气钯碳还原烯烃、硼氢化钠还原羰基,得到奥贝胆酸关键异构体杂质6β-乙基-鹅去氧胆酸(OCA-β),两步产率分别为46%和78%。使用1 H NMR、13C NMR、HRMS等确证其结构。该方法具有操作简单、反应条件温和、产率高等优点。     

猪胆粉中猪去氧胆酸的提取、鉴定和含量测定

为建立猪胆粉中猪去氧胆酸的提取、鉴定及含量测定方法,采用皂化、脱色、酸化的方法制得猪去氧胆酸粗提物,运用薄层色谱法(TLC)鉴定后,并进一步对其含量进行测定。制得的猪去氧胆酸在3.5185~21.111μg范围内具有良好的线性关系,线性方程为Y=1.498X+2.892(r=0.9998),确定猪去氧胆酸的含量为33.23%。猪去氧胆酸的提取方法简单易行,操作方便,检测方法准确可靠、重复性好,可用于猪去氧胆酸的质量控制。     

多羟基甾醇的合成研究——胆甾-3,7,24-三醇的合成

以去氧胆酸为起始原料,与甲醇反应得到去氧胆酸甲酯,然后在超声波环境下用硼氢化钠-聚乙二醇400-四氢呋喃体系还原得到胆甾-3,7,24-三醇.     

双烯醇酮醋酸酯主要杂质的合成研究

将双烯醇酮醋酸酯溶于苯中,加入过氧化叔丁醇、重铬酸吡啶盐、硅藻土,于室温反应2~3 h,得到杂质粗品;粗品经层析柱分离,乙醇、二氯甲烷精制,得到主要杂质化合物Ⅰ;其结构经1H NMR和ESI-MS确证。     

猪去氧胆酸的提取方法的比较及工艺优化

比较了目前猪去氧胆酸的提取方法,对部分工艺进行了优化,提出新的更适用于工业生产的猪去氧胆酸提取方法。尝试了乙酸乙酯或丙酮重结晶法,均难得到满意的效果,提出了两种新的提取方法:循环利用法和苯胺复合物法。结果表明,两种方法均得到了纯度较高的猪去氧胆酸,经HPLC测定含量在99%以上。新的提取方法提高了产物的收率,产物纯度高,且适用于工业生产。     

那他霉素光降解杂质的制备与结构鉴定

将那他霉素精品在光照强度5 000 Lx下进行光降解,得到那他霉素光降解杂质粗品,采用制备液相色谱法对那他霉素光降解杂质粗品进行分离纯化,并通过MS和NMR等分析手段对其结构进行鉴定,确定该光降解杂质为那他霉素的C12位差向异构体。     

高含量猪去氧胆酸精制工艺的研究

目的:研究以低含量猪去氧胆酸为原料,精制高含量猪去氧胆酸的最佳工艺。方法:采用正交设计L_9(3~4)方法,筛选出最佳除杂工艺,采用高效液相色谱法,测定猪去氧胆酸的含量,考察了水用量、pH、澄清剂的添加量,对猪去氧胆酸收率的影响,优选出合理除杂工艺;考察乙酸乙酯、活性炭用量和回流时间对猪去氧胆酸含量的影响,选出最佳精制工艺条件。结果:水量是10倍量、pH 11～12,澄清剂质量分数1.5%为最佳除杂工艺;乙酸乙酯用量为12倍量、活性炭的质量分数为3%,回流时间1 h为最佳的精制工艺。结论:采用正交设计筛选出的最佳精制工艺稳定可行,满足注射剂用药的要求。     

Dietary Hyodeoxycholic Acid Exerts Hypolipidemic Effects by Reducing Farnesoid X Receptor Antagonist Bile Acids in Mouse Enterohepatic Tissues

Mice were fed a control diet or a diet supplemented with hyodeoxycholic acid, the most abundant bile acid contained in pig bile, for 4 weeks, after which their serum and livers were collected. The contents of total fatty acids of serum and liver cholesteryl esters, and of liver triglycerides, were reduced following the administration of the hyodeoxycholic acid‐supplemented diet, which was mainly due to the reductions in the contents of monounsaturated fatty acids. Free cholesterol contents in the serum and liver were not changed by hyodeoxycholic acid administration. Hyodeoxycholic acid administration reduced the gene expression levels of sterol regulatory element binding protein 1c, acetyl‐CoA carboxylase, fatty acid synthase, and stearoyl‐CoA desaturase‐1. Hyodeoxycholic acid administration markedly changes the ratio of FXR‐antagonist/FXR‐agonist bile acids in the enterohepatic tissues of the mice (1.13 and 7.60 in hyodeoxycholic acid and control diet groups, respectively). Our findings demonstrate that hyodeoxycholic acid administration exerts the hypolipidemic effect in mice, in which downregulations of de novo lipogenesis and desaturation of saturated fatty acids are suggested to play important roles. In addition, regulation of FXR activation through the selective modification of the enterohepatic bile acid pool may be involved in the hypolipidemic effect of hyodeoxycholic acid administration.     

Dissolution of cholesterol gallstones by bile acids in the prairie dog

The effect of chenodeoxycholic acid, ursodeoxycholic acid and hyodeoxycholic acid on gallstone dissolution was studied in the prairie dog. Cholesterol gallstones were found in all animals after feeding a semipurified diet plus 1.2% cholesterol for six wk. Gallstone regression was examined by feeding a chow diet containing the bile acids (chenodeoxycholic acid, ursodeoxycholic acid or hyodeoxycholic acid) alone (30 mg/kg/day) or in combination (chenodeoxycholic acid plus ursodeoxycholic acid) for an additional six wk. Chenodeoxycholic acid was effective in dissolving established cholesterol gallstones (two out of 16 animals still had stones) and cholesterol crystals (six out of 16 animals had crystals); the hydrophilic bile acids, ursodeoxycholic acid and hyodeoxycholic acid, were ineffective in the six-wk regression study. The lithogenic indices averaged 1.09 at the end of the induction period: all biles became unsaturated with respect to cholesterol after the six-wk regression period (group 1, 0.82; group 2, 0.66; group 3, 0.81; group 4,0.84; group 5, 0.66). Cholesterol levels in liver, plasma and bile were elevated after the six-wk induction phase (4.59 mg/g, 610 mg/dl and 0.36 mg/ml, respectively) but returned to near normal levels after the six-wk regression period. Biliary bile acids contained increased levels of the dietary bile acid administered to each group. This experiment shows that relatively hydrophobic bile acids may be more effective than hydrophilic bile acids for gallstone dissolution during the period studied.     

3-甲基庚酸合成工艺改进

对3-甲基庚酸的合成工艺进行了改进,采用仲丁醇和2-丁烯酸反应生成2-丁烯酸仲丁酯来保护羧基,然后再与正丁基溴化镁反应制得3-甲基庚酸仲丁酯,最后在碱性条件下脱去保护基得到产品3-甲基庚酸。合成路线新颖,所得产物收率高,并用1HNMR、元素分析和IR进行了结构分析为目标产物。     

GC-MS and 13C NMR Investigation of Lead Zirconate Titanate Precursor Sols for Fiber Preparation

Different macroscopic properties of PZT fibers have been obtained when using acetic acid and methacrylic acid to modify the PZT precursor. In order to clarify the role of the acids the molecular structure of the acidified PZT precursors was investigated and compared by gas chromatography-mass spectrometry, Fourier transform infrared, ¹³C nuclear magnetic resonance (NMR) spectroscopy (solution and solid state ¹³C NMR) and the reason for obtaining long PZT fibers is discussed. The results indicate that when methacrylic acid was used, long gel and ceramic fibers have been obtained because strongly co-ordinating carboxylate groups of methacrylic acid were formed. Linear chains, like those of methacrylic acid propyl ester and methacrylic acetate, have been formed in the PZT precursor sols. In addition, after heat treatment the polymer decomposed quickly so that pure perovskite could be obtained at low temperature in the PZT fibers. When acetic acid was used short fibers were obtained. Acetic acid may act as chelate agent to form oxo acetate in the precursors; this oxo acetate nature also resulted in PZT fibers drawing. However, the longest gel and ceramic fibers have been prepared from precursors with methacrylic acid.     

Identification and quantitation of cholanoic acids in hepatic and extra-hepatic tissues of rat

Tissues of rats were examined for the presence of cholanoic acids. Quantitation of extraction, deconjugation, and isolation were verified by use of radioactive standards. Identification was made by thin layer and gas liquid chromatographic comparison to standards and mass spectrometry. All tissues examined were found to contain several conjugated cholanoic acids. Liver contained primarily cholic acid and peripheral tissues primarily dihydroxy compounds, mainly hyodeoxycholic acid.     

Control of ordered structure and morphology of cubic mesoporous silica SBA-1 via direct synthesis of thiol-functionalization

Well-ordered cubic mesoporous silicas SBA-1 functionalized with thiol groups have been synthesized via co-condensation of tetraethoxysilane (TEOS) and 3-mercaptopropyltrimethoxysilane (MPTMS) templated by cetyltriethylammonium bromide (CTEABr) under strongly acidic conditions. Various synthesis parameters such as HCl concentration, synthesis temperature, and time for hydrothermal treatment were systematically investigated as a function of MPTMS contents. The materials thus obtained were characterized by a variety of techniques including powder X-ray diffraction (XRD), solid-state ¹³C and ²⁹Si NMR spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and nitrogen sorption measurements. Direct evidence of the presence of chemically attached thiol moieties was provided by solid-state ²⁹Si and ¹³C NMR spectroscopy. A high degree of structural ordering was still retained when MPTMS loading was incorporated up to 20 mol% in the synthesis mixture. Increasing the synthesis temperature and the time for the hydrothermal treatment not only increased the degree of framework cross-linking, but also did not lead to the undesirable phase transformation as often observed in the conventional synthesis of pure silica SBA-1. SEM results reveal that the morphology of thiol-functionalized SBA-1 depends on the HCl concentration used in the synthesis. The sample prepared with a low acid concentration exhibits a highly isotropic morphology with more facets than that of pure silica SBA-1, whereas it changes to a spherical shape as the acid concentration is increased. The maximum content of the attached thiol group (–SH) in the mesoporous framework is 2.39 mmol/g. The thiol-functionalized SBA-1 mesoporous materials are efficient Hg²⁺ adsorbents.     

Effect of chitosan feeding on intestinal bile acid metabolism in rats

The effect of chitosan feeding (for 21 days) on intestinal bile acids was studied in male rats. Serum cholesterol levels in rats fed a commercial diet low in cholesterol were decreased by chitosan supplementation. Chitosan inhibited the transformation of cholesterol to coprostanol without causing a qualitative change in fecal excretion of these neutral sterols. Increased fiber consumption did not increase fecal excretion of bile acids, but caused a marked change in fecal bile acid composition. Litcholic acid increased sigificantly, deoxycholic acid increased to a leasser extent, whereas hyodeoxycholic acid and the 6β-isomer and 5-epimeric 3α-hydroxy-6-keto-cholanoic acid(s) decreased. The pH in the cecum and colon became elevated by chitosan feeding which affected the conversion of primary bile acids to secondary bile acids in the large intestine. In the cecum, chitosan feeding increased the concentration of α-,β-, and ω-muricholic acids, and lithocholic acid. However, the levels of hyodeoxycholic acid and its 6β-isomer, of monohydroxy-monoketo-cholanoic acids, and of 3α, 6ξ, 7ξ-trihydroxy-cholanoic acid decreased. The data suggest that chitosan feeding affects the metabolism of intestinal bile acids in rats.     

(E)-4-吗啉-2-丁烯酸盐酸盐的合成

以吗啉为起始原料,与溴丁烯酸甲酯反应,得到4-吗啉-2-丁烯酸甲酯,然后在二氧六环中用浓盐酸水解,得到目标产物,总收率为49.65%,产物结构经过1H NMR确证。