精制白喉标准毒素及精制锡克试验毒素的制备与检定

采用纯度为2000Lf/mgPN以上的精制白喉毒素,加到甘油明胶缓冲液中,制成约1000MLD/ml的精制白喉标准毒素。放置4℃保存10年,其MLD/Lf仅下降13.6％,证明稳定性良好;而原制白喉标准毒素在同样条件下MLD/Lf竟下降94.6％,稳定性很差,其放置的前3年,MLD/Lf呈急剧直线下降,后7年则呈缓慢下降。用精制白喉标准毒素共生产精制锡克试验毒素10批,经检定,MRD/ml和MLD/ml皆符合我国规程要求;结合力,7批符合英国药典规定,另3批经20％稀释亦能达到上述要求。原制锡克试验毒素的结合力一般为精制的2～5倍。     

半月要闻

年产３０００吨级精制咪唑项目 建成投产由上海三微精细化工厂投资兴建的年产３０００吨级精制咪唑项目最近建成投产，生产的咪唑颜色雪白、纯度达到９９．５％，填补了国内空白，改写了我国精制咪唑依靠进口的历史。 用于环氧树脂固化剂、医药中间体和农药杀虫剂原料的咪唑，以前国内生产的纯度只有９５％左右，色泽偏黄，而９９．５％的精制咪唑一有依靠从巴斯夫公司进口。上海三微精细化工厂瞄准国内外市场，吸引人才，研究开发精制咪唑项目，并引进国外关键生产工艺设备，结合国内特点，进行攻关创新，终于生产出了具有较大市场的精制咪…     

硝酸胍的精制

在硝酸胍粗品中加入无机碱进行精制，精制收率可达９５％，母液循环批次可增至２１批以上。     

减压蒸馏法精制一甲胺基甲酰氯

光气和一甲胺反应制备一甲胺基甲酰氯，产品纯度一般在85％～90％，通过减压蒸馏精制提纯后可提高到92％～94％。本文介绍了减压蒸馏法精制一甲胺基甲酰氯的工艺原理、操作步骤及精制效果。     

国标微生物法与试剂盒法检测维生素胶囊叶酸含量的比对

叶酸,又名维生素B9,是人体必需的一种水溶性B族维生素。本文选取维生素胶囊为样品,采用叶酸国标法和试剂盒法,参考《中国药典》2015版四部通则9101与文献,从叶酸含量试验结果的重复性和回收率分析比对两个方法,实验结果表明,国标法比试剂盒法更适合用于检测维生素胶囊的叶酸含量。     

苯巴比妥(Ph.Eur.7.1)的合成工艺研究

进行了苯巴比妥的合成工艺研究,探讨了甲醇钠滴加温度、甲乙醇回收终点温度、精制投料配比的影响,对工艺控制点进行了优化,使产品达到欧洲药典Ph.Eur.7.1的质量要求。     

聚醚多元醇精制工艺改进

在聚醚多元醇中和精制过程中，加入无机盐水合物的ＢＨＴ，使中和过程涌在水含量小于１％条件下进行。工业试验结果表明，精制时间可缩短２０％以上，提高了生产效率。聚醚多元醇质量符合要求。     

用MTBE尾气作烷化剂取代丙烯对富集均三甲苯的精制

采用反应分离方法，用MTBE尾气对富集均三甲苯进行精制，在选定了催化剂的加入量、反应温度和气速后，MTBE尾气对富集均三甲苯的精制起到了较佳的作用，甲乙苯的转化率超过94％，均三甲苯的产率高于110％，反应液中均三甲苯与C9芳烃的质量比大于98．6％。     

精制棉废水处理工艺研究

精制棉废水呈碱性，成分复杂，含有难生物降解的物质，CODCr值及色度均高，属于难处理高浓度有机废水。精制棉废水适宜进行物化处理：调整pH到3左右，加进助凝剂，用压缩空气搅拌，经气浮沉淀色度降低70％以上，CODCr降低50％以上。     

维生素K_4的合成

以２－甲基－１，４－萘醌、醋酸酐为主要原料一步合成维生素Ｋ４。考察了回流温度与回收率的关系，用水代替部分乙醇（９５％）精制的精制方法及经济效益。得出了用１０％水代替乙醇精制是可行的，给出了实际操作时各主要原料的投入比。实验表明此合成路线简单，回收率高达７０％～７４％。     

Iron, folic acid and vitamin B12 deficiencies related to anemia in adolescents from a region with a high incidence of congenital malformations in Venezuela

Since in recent years for certain age groups, the main cause of anemia is not iron deficiency, we intended to study the effect of iron, folic acid and vitamin B12 deficiencies on anemia prevalence in adolescents from Venezuela. One hundred adolescents aged between 12 and 19 years participated in the study. Each subject was interviewed about antecedents and habits and a physical examination and a 24-hour food recall questionnaire were performed. From a blood sample, hemoglobin and hematocrit concentrations were determined and serum was separated for quantification of ferritin, folic acid and vitamin B12 concentrations. Prevalence of anemia was 78% and for iron, folic acid and vitamin B12 deficiencies were 34.66, 90.9 and 18.18%, respectively. From anemic cases, 35.89% presented iron deficiency, while 91.02% presented folic acid deficiency. Only 19.23% of adolescents with anemia presented also vitamin B12 deficiency, but all the cases with vitamin B12 deficiency, were anemic. Simultaneous iron and folic acid deficiencies affected 30.76% of anemic cases. The high prevalence of deficiencies found in this work could be explained by insufficient intake and inadequate food habits. The prevalence of anemia was associated to folic acid deficiency rather than to iron deficiency, due to the high prevalence of folic acid deficiency. The high prevalence of nutritional deficiencies found in this work, especially regarding folic acid deficiency, require immediate interventions.     

Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations

Folic acid is presently the mainstay of treatment for most subjects with elevated plasma homocyst(e)ine concentrations [Plasma or serum homocyst(e)ine, or total homocysteine, refers to the sum of the sulfhydryl amino acid homocysteine and the homocysteinyl moieties of the disulfides homocystine and homocystein-cysteine, whether free or bound to plasma proteins.] Changes in homocyst(e)ine in response to folic acid supplementation are characterized by considerable interindividual variation. The purpose of this study was to identify factors that contribute to heterogeneity in short-term responses to folic acid supplementation. The effects of folic acid supplementation (1 or 2 mg per day) for 3 wk on plasma homocyst(e)ine concentrations were assessed in 304 men and women. Overall, folic acid supplementation increased mean plasma folate 31.5±98.0 nmol/L and decreased mean plasma homocyst(e)ine concentrations 1.2±2.4 μmol/L. There was evidence of substantial interindividual variation in the homocyst(e)ine response from ?18.5 to +7.1 μmol/L, including an increase in homocyst(e)ine in 20% of subjects (mean increase 1.5±1.4 μmol/L). Basal homocyst(e)ine, age, male gender, cigarette smoking, use of multivitamins, methylene tetrahydrofolate reductase, and cystathionine β-synthase polymorphisms accounted for 47.6% of the interindividual variability in the change in homocyst(e)ine after folic acid supplementation, but about 50% of variability in response to folic acid was not explained by the variables we studied.     

Prevalence of anemia and deficiencies of iron, folic acid and vitamin B12 in an indigenous community from the Venezuelan Amazon with a high incidence of malaria

The objective of this work was to determine the prevalence of anemia and deficiencies of iron, folic acid and vitamin B12 in Betania del Topocho, a Piaroa community from Estado Amazonas, Venezuela, a zone with a high incidence of malaria. The group studied included 184 subjects of all ages that assisted to the local health center for malaria diagnosis. Analysis performed included hematology by coulter counter, ferritin quantification by ELISA with monoclonal antibodies and folic acid and vitamin B12 determinations by an immunoradiometric assay. It was found that the prevalence of anemia was 89.6% and deficiencies of iron, folic acid and vitamin B12 affected 37.1,70.3 and 12.4% of the population studied, respectively. Plasmodium infection was detected by molecular diagnosis in 53.2% of the cases, and 86% of them were anemic. The highest incidence of anemia was found in children, with a prevalence of 100% in infants of both sexes. The high prevalence of anemia, iron and folic acid deficiencies found, indicates an important health and nutrition problem that should be immediately and properly addressed. The number of cases of anemia due to iron deficiency could be underestimated, since ferritin concentration increased as a acute phase protein, although prevalence data was also analyzed with a cutoff point of 30 microg/L for ferritin concentration.     

Voltammetric behavior study of folic acid at phosphomolybdic-polypyrrole film modified electrode

The electrochemical behavior of folic acid at the Keggin-type phosphomolybdate (PMo₁₂) doped polypyrrole (PPy) film modified glassy carbon electrode (PMo₁₂-PPy/GCE) was studied. PMo₁₂ doped PPy modified electrodes were achieved during the electrochemical preparation of the polymer films in aqueous solution. The redox behavior of the modified electrode was described by cyclic voltammetry. The electrochemical behavior of folic acid at PMo₁₂-PPy/GCE was studied by 0.5 order differential voltammetry. Numerous factors affecting the reduction peak currents of folic acid at PMo₁₂-PPy/GCE were optimized to maximize the sensitivity. The results showed that folic acid had high inhibitory activity toward the reduction of modified electrode in 0.01 M H₂SO₄. The reduction peak currents were directly proportional to the concentration of folic acid from 1.0 × 10⁻⁸ to 1 × 10⁻⁷ M with correlation coefficient of 0.9976, a detection limit of 1.0 × 10⁻¹⁰ M of folic acid was estimated. From the inhibitory effect of folic acid on PMo₁₂-PPy/GCE, the apparent formation constant of folic acid with the modified film was estimated. This modified electrode showed excellent sensitivity and stability for the determination of folic acid. The response mechanism of folic acid at PMo₁₂-PPy/GCE was discussed in detail.     

A multi-nutrient supplement reduced markers of inflammation and improved physical performance in active individuals of middle to older age: a randomized, double-blind, placebo-controlled study

Background

Evidence suggests that folate deficiency may be causatively linked to depressive symptoms. However, little is known on the status of use of folic acid and vitamin supplements among people with mental disorders. This study examined the prevalence and the likelihood of use of folic acid or vitamin supplements among adults with depression and anxiety in comparison to those without these conditions.

Methods

Using data from 46, 119 participants (aged ≥ 18 years) in the 2006 Behavioral Risk Factor Surveillance System survey, we estimated the adjusted prevalence and odds ratios with 95% confidence intervals for taking folic acid and vitamin supplements among those with ever diagnosed depression (n = 8, 019), ever diagnosed anxiety (n = 5, 546) or elevated depressive symptoms (n = 3, 978, defined as having a depression severity score of ≥ 10 on the Patient Health Questionnaire-8 diagnostic algorithm).

Results

Overall, women were more likely than men to take folic acid supplements 1-4 times/day (50.2% versus 38.7%, P < 0.001) and vitamin supplements (62.5% versus 49.8%, P < 0.001). After multivariate adjustment, men with ever diagnosed depression or anxiety were 42% and 83%, respectively, more likely to take folic acid supplements < 1 time/day; 44% and 39%, respectively, more likely to take folic acid supplements 1-4 times/day; and 40% and 46%, respectively, more likely to take vitamin supplements compared to men without these conditions (P < 0.05 for all comparisons). Women with ever diagnosed depression were 13% more likely to take folic acid supplements 1-4 times/day and 15% more likely to take vitamin supplements than women without this condition (P < 0.05 for both comparisons). Use of folic acid and vitamin supplements did not differ significantly by elevated depressive symptoms in either sex.

Conclusion

The prevalence and the likelihood of taking folic acid and vitamin supplements varied substantially by a history of diagnosed depression among both men and women and by a history of diagnosed anxiety among men, but not by presence of elevated depressive symptoms in either sex.     

Poly(2-hydroxyethylmethacrylate-co-2-folate ethylmethacrylate) and Folic acid/Poly(2-hydroxyethylmethacrylate) Solid Solution: Preparation and Drug Release Investigation

Poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) was synthesized by free radical polymerization of 2-hydroxyethylmethacrylate with 2-folatethylmethacrylate and folic acid/poly(2-hydroxyethylmethacrylate) solid solutions was prepared by mixing folic acid with poly(2-hydroxyethylmethacrylate) using the solution casting method. The structure and the homogeneity distribution of folic acid in the polymer matrix are characterized by different methods. The diffusion behaviors of water and folic acid through poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) and poly(2-hydroxyethylmethacrylate) matrixes were found obey to the Fick models. The in vitro cytotoxicity assessed by microculture tetrazolium test assay and the antioxidant activity of poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) systems determined by 1,1-diphenyl-2-picryl-hydrazyl method revealed no significant toxicity of these systems and has excellent free radical scavenger property which can be as safe candidate in drug-carrier system. The solubility enhancement of folic acid in different pH media is also investigated and the results obtained reveal a maximum of 399–400?mg?L^?1. The release dynamic of folic acid from the poly(2-hydroxyethylmethacrylate-co-2-folatethylmethacrylate) containing 5?mol% of folic acid and that from folic acid/poly(2-hydroxyethylmethacrylate) system containing 10?mol% of folic acid have the best intestine/stomach ratio.     

Monitoring the functionalization of single-walled carbon nanotubes with chitosan and folic acid by two-dimensional diffusion-ordered NMR spectroscopy

A conjugate between single-walled carbon nanotubes, chitosan and folic acid has been prepared. It was characterized by diffusion ordered two-dimensional hydrogen-1 nuclear magnetic resonance and hydrogen-1 nuclear magnetic resonance spectroscopy which revealed the presence of a conjugate that was generated by the linkage between the carboxyl moiety of the folic acid and the amino group of the chitosan, which in turn was non-covalently bound to the single-walled carbon nanotubes. The obtained diffusion coefficient values demonstrated that free folic acid diffused more rapidly than the folic acid conjugated to single-walled carbon nanotubes–chitosan. The values of the proton signal of hydrogen-1 nuclear magnetic resonance spectroscopy and two-dimensional hydrogen-1 nuclear magnetic resonance spectroscopy further confirmed that the folic acid was conjugated to the chitosan, wrapping the single-walled carbon nanotubes.     

Integral bread development with soybean, chia, linseed, and folic acid as a functional food for women

Six bread formulations were developed, using different proportions of whole-wheat flour, chia seeds and flaxseed flour. All of our formulations were added with folic acid. Sensorial and texture evaluations were performed, showing good acceptance of the products. Proximal chemical analysis was carried out; in addition, the following parameters were determined: calcium, phosphorus, total dietary fiber, folic acid, water hydration capacity, Glucose Dialysis Retardation Index (GDRI) and fatty acids. The results obtained showed higher protein levels in the developed breads (23.23-30.24 (g/100g dry matter) as compared to a control (21.00% of proteins in bread elaborated without chia or flaxseed). Furthermore, the breads contained 10.07-12.15 of lipids (g/100g dry matter) (linoleic acid: 2.43-4.05%; linolenic acid: 1.12-4.46 %; oleic acid: 2.93-6.13 %), GDRI values were between 89.1 and 98.1 % and folic acid was in the range 699.44 - 991.3 (microg/100g dry matter). The same parameters were determined in the chia seed and in the flaxseed flour. It was concluded that; due to their high levels of protein, insaturated fatty acids (omega-3 and omega-6), dietary fiber and folic acid, these breads have a high nutritional value, so they could have special benefits for woman.     

半胱胺改性叶酸衍生物的制备及其性能研究

在N,N-二环己基碳酰亚胺(DCC)和N-羟基琥珀酰亚胺(NHS)共同催化下制备出半胱胺改性叶酸衍生物,在pH=8的稀氨水溶液中,对纳米金和叶酸衍生物进行偶联。结果表明,叶酸的羧基与半胱胺的巯基发生了反应,叶酸衍生物具有荧光性能,并与纳米金粒子有吸附作用,在叶酸靶向肿瘤诊断治疗方面具有潜在的应用价值。     

HPLC法测定叶酸片溶出度

采用高效液相色谱（HPLC）法进行叶酸片的溶出度测定。采用小杯法,色谱柱为Agilent Hypersil C18（25 cm×4.6 nm,5μm）,流动相为pH=5.0的磷酸盐缓冲液,检测波长为280 nm,流速为1.2 mL/min。结果表明,采用HPLC法测定叶酸片溶出度,分离度好,峰形对称,保留时间短,辅料不干扰,测得叶酸回收率为100.6%,RSD=1.04%（n=9）。该法简便,结果准确。