婴幼儿腹泻的轮状病毒感染与乳糖不耐受的研究

目的探讨婴幼儿腹泻患者的轮状病毒感染和乳糖不耐受及相互关系,帮助临床鉴别诊断婴幼儿腹泻病因。方法对本院门诊及住院年龄在3岁以下555例腹泻患儿粪便均做常规检测、细菌培养、轮状病毒抗原检测、还原糖检测。结果轮状病毒肠炎409(73.7%)例,乳糖不耐受症349(62.9%)例,轮状病毒合并乳糖不耐受291例,占轮状病毒肠炎患者的71.1%。结论秋冬季婴幼儿腹泻主要病原体为轮状病毒,而轮状病毒肠炎多数有继发乳糖不耐受。     

Form conversion of anhydrous lactose during wet granulation and its effect on compactibility

The purpose of this study was (a) to evaluate the factors affecting the form conversion of anhydrous lactose to the monohydrate form during wet granulation using water as the granulating agent and (b) study the effect of lactose form conversion on its compaction properties. A two-level full factorial design with two center points was used to evaluate the factors affecting form conversion. The three variables evaluated were percentage of microcrystalline cellulose (low 0 and high 20), water to intragranular solids ratio (low 0.10 and high 0.18) and drying conditions (tray drying and fluid bed drying). The presence of microcrystalline cellulose in the formulation did not provide any benefit in reducing the percent lactose conversion. But, the conversion was significantly reduced by decreasing the amount of water added to the granulation and/or by decreasing the drying time, using a fluid bed dryer compared to a tray dryer. In the second part of the study, complete conversion of the anhydrous lactose to monohydrate was achieved by storing the anhydrous form under 25 °C/97% RH for 4 weeks. Physical characterization (compactibility, surface area and surface morphology) was performed on the form converted material and compared to the as received anhydrous lactose. The physical characterization results indicated that even though anhydrous lactose undergoes complete form conversion to monohydrate form under high humidity and/or during wet granulation, it retains its inherent higher as received material compactibility and the BET surface area and porosity of the form converted material are higher than that of the as received anhydrous lactose.     

注射用乳糖酸阿奇霉素治疗小儿支气管肺炎效果观察

目的探讨注射用乳糖酸阿奇霉素治疗小儿支气管肺炎的临床疗效及安全性。方法回顾性分析2008年2月至2010年5月期间,在我院收治的80例小儿支气管肺炎患儿,随机分为治疗组与对照组,每组各40例。治疗组给予注射用乳糖酸阿奇霉素,对照组给予注射用阿莫西林克拉维酸钾,密切观察两组患者的临床疗效。结果乳糖酸阿奇霉素治疗小儿支气管肺炎的总有效率高于对照组的总有效率,且乳糖酸阿奇霉素组的不良反应发生率明显低于对照组。结论乳糖酸阿奇霉素是治疗小儿支气管肺炎临床疗效确切有效、安全性高的抗生素的方法。     

Quantitative analysis of amorphous content of lactose using CCD-Raman spectroscopy

A Raman spectroscopy method was developed for the quantification of the amorphous content of lactose. Both physical mixtures and spray-dried samples were used and the results were compared with the IMC determinations. Sample inhomogeneities were averaged out by collecting multiple spectra from each sample, and the total measurement time remained below 10 min due to the high sensitivity of the CCD-Raman spectrometer used in the measurements. The obtained calibration error (SEC) for the physical mixtures was 1.3% (w/w) in the 0–100% amorphous content range and was reduced to 0.2% (w/w) in the 0–10% range of more practical interest. The crystallization heat values of the spray-dried samples showed a linear correlation with the Raman quantifications in the amorphous content range of 0–80%, but saturated over the 80% concentration. This finding suggests a reference value of ca. 60 J/g for the spray-dried samples, instead of the crystallization heat of amorphous lactose (ca. 50 J/g) valid in the IMC determinations of physical mixtures.     

乳糖诱导人胰岛素样生长因子-1在大肠杆菌中的表达

目的以含有人源性胰岛素样生长因子-1（hIGF-1）基因的大肠杆菌DH5a为研究对象,研究以乳糖作为诱导剂时目的融合蛋白的表达规律。方法利用可表达hIGF-1的工程菌,研究乳糖代替IPTG诱导大肠杆菌在不同条件下表达目的蛋白的一般规律．并优化表达条件,表达结果借助SDS-PAGE等方法进行分析。结果乳糖可诱导hIGF-1在大肠杆菌中的表达．最优表达条件为37℃下重组菌株生长至OD600值为0．7时加入诱导浓度为0．8％的乳糖继续诱导4h。诱导的目的融合蛋白相对表达量能够达到占总蛋白的40-60％水平,接近IPTG的诱导表达水平。结论乳糖能够代替IPTG作为诱导剂成功诱导hIGF-1在大肠杆菌中的表达。     

A material with opioid activity in bovine milk and milk products

Summary Chloroform-methanol extracts of lyophilized milk, of commercially available dried milk or baby food and of casein digests were tested for opioid activity on the guinea-pig ileum longitudinal muscle-myenteric plexus preparation. Compounds with opioid activity — which proved to be resistant to peptidases — were detected in certain batches of baby food, casein digest, and cow milk in considerably varying amounts.     

Studies on tableting properties of lactose

The consolidation and compaction behaviour of sieve fractions of crystalline -lactose monohydrate were studied. From mercury porosimetry measurements tablet pore surface areas were derived. At a certain compaction load it appeared that tablets compressed from small particles were generally stronger and showed a larger surface area than compacts prepared from coarse sieve fractions. By plotting compact strength against pore surface area, a unique linear relationship was obtained. From these results it can be concluded that the actual tablet surface area, being a function of both the initial particle size and applied compaction pressure, is responsible for the compact strength.     

乳糖-纤维素复合辅料的制备及其性能评价

目的制备乳糖-纤维素复合辅料,用于直接压片技术。方法通过乳糖结晶工艺制备质量比为75∶25的乳糖-纤维素复合辅料。比较复合辅料与简单混合物的粉体学性质以及片剂质量。结果复合辅料显示出较好的流动性、填充性和可压性,对可压性差的药物具有很好的稀释作用。结论乳糖-纤维素复合辅料通过对乳糖及粉状纤维素物理性能的改变,更加适用于直接压片工艺。     

Change in porosity parameters of lactose, glucose and mannitol granules caused by low compression force

The change in porosity parameters, i.e., total pore volume, porosity percentage and pore volume size distribution of lactose, glucose and mannitol granules caused by compression with a low force was investigated. In compression, fragmentation of lactose and glucose granules increased total pore volume and porosity percentage, whereas the total pore volume and porosity percentage of mannitol granules was clearly decreased. This was due to the highly porous structure of mannitol granules, which densified easily in compression. Lactose and glucose granules were shown to resist deformation more. The pore volume size distributions of lactose and glucose tablets showed that large pores ( > 14 μm) decreased in size. For mannitol tablets, the large pores vanished and simultaneously the small granule pores ( < 14 μm) reduced in size. The features of the pore structure of granules were detected in the pore volume size distributions of compressed tablets. Mercury porosimetry, assisted by scanning electron microscopy, was shown to be an adequate method to evaluate the deformation of granules in compression.     

Exposure assessment of mycotoxins in cow's milk in Argentina

A stochastic simulation model was developed to carry out the first quantitative risk exposure assessment of the mycotoxin level in cow's milk produced in Argentina. The prevalence and concentration of aflatoxin M1 (AFM1), deoxynivalenol (DON) and zearalenone (ZEA) were modeled at various stages through milk processes complying with Argentinean practices. Concentration of AFM1 (0.059ppb), DON (0.338ppb) and ZEA (0.125ppb) in dairy milk were estimated. The proportion of feed samples that exceeded the maximum level accepted by European regulations for AFB1, DON and ZEA were estimated at 25.07%, 0.0% and 8.9%, respectively. The percentage of milk samples that exceeded the maximum level accepted for AFB1 by the MERCOSUR (0.5ppb) and the European Union regulations (0.05ppb) were 0.81 and 32.65, respectively. The probability distribution of AFM1 concentration in milk was affected by the carry-over rate equations applied in the model. Mycotoxin levels in corn silage and concentrated feeds were the factors most correlated with mycotoxin concentrations in milk. Therefore, agricultural practices, crop management and feed production require prompt attention regarding mycotoxin issues.     

乳糖诱导表达重组人甲状旁腺激素rhPTH(1-34)

目的研究以乳糖代替异丙基硫代半乳糖苷(IPTG)诱导表达重组人甲状旁腺激素的可行性。方法对乳糖浓度、诱导时间及发酵培养方式进行研究,确定了乳糖诱导的最佳条件。结果 0.6%的乳糖诱导4 h,目的蛋白的表达量约占菌体总蛋白的56.8%,采取分批补料培养方式,5 L发酵罐中蛋白表达量达到42.6%。结论乳糖能作为诱导剂诱导rhPTH(1-34)在大肠杆菌中的表达。     

出生后呕吐为表现的牛奶蛋白过敏病儿 1例

目的探讨牛奶蛋白过敏病儿饮食治疗经验。方法回顾分析 2020年 3月中国科学技术大学附属第一医院收治的 1例以生后呕吐为表现的牛奶蛋白过敏病儿致生长发育迟缓的临床资料,对其治疗进行总结探讨。结果该例病儿生后即出现频繁奶后呕吐,入院后详细询问病史,并完善相关检查,诊断为牛奶蛋白过敏,予以更换氨基酸奶粉喂养后,病儿呕吐症状消失,体质量增长。结论限制饮食中牛奶蛋白的摄入是牛奶蛋白过敏病儿治疗的关键。     

An evaluation of microcrystalline cellulose and lactose excipients using an instrumented single station tablet press

The objective of this study was to evaluate the effects of microcrystalline cellulose of two particle sizes from two suppliers at two concentration levels, in combination with anhydrous lactose or Fast-Flo lactose on various properties of hydrochlorothiazide tablets. The powder blends before compression were evaluated for flow, density and compressibility. Tablets were compressed at three hardnesses and evaluated for friability, disintegration and hydrochlorothiazide dissolution. Powder blends containing Fast-Flo lactose exhibited a flow rate predicted to be sufficient for high-speed tableting whereas only when anhydrous lactose was used with the larger particle size microcrystalline cellulose was the same degree of flowability obtained. Density was affected by the concentration of microcrystalline cellulose. Fast-Flo lactose markedly increased density at the lower level of microcrystalline cellulose concentration. No difference was found in blend compressibility as a result of microcrystalline cellulose particle size or supplier source at medium to high tablet hardness levels, however, anhydrous lactose blends were more compressible than Fast-Flo lactose blends. At all hardness levels, tablets from all blends exhibited excellent friability. In most instances, tablet disintegration seemed to be more rapid when Fast-Flo lactose was present. Hydrochlorothiazide dissolution from all tablets easily met USP specifications. The microcrystalline cellulose from the two sources are interchangeable within particle size classification. Anhydrous lactose is more compressible than Fast-Flo lactose but Fast-Flo lactose is more flowable and its use results in more rapid drug dissolution at the higher microcrystalline cellulose levels.     

Compatibility studies of acyclovir and lactose in physical mixtures and commercial tablets

This study documents drug-excipient incompatibility studies of acyclovir in physical mixtures with lactose and in different tablet brands. Differential scanning calorimetry (DSC) was initially used to assess compatibility of mixtures. The Fourier-transform infrared (FTIR) spectrum was also compared with the spectra of pure drug and excipient. Although DSC results indicated incompatibility with lactose, FTIR spectra were mostly unmodified due to overlapping peaks. Samples of isothermally stressed physical mixture were stored at 95 °C for 24 h. The residual drug was monitored using a validated high-performance liquid chromatography (HPLC) assay and data fitting to solid-state kinetic models was performed. The drug loss kinetics followed a diffusion model. The aqueous mixture of drug and excipient was heated in order to prepare an adduct mixture. HPLC analysis revealed one extra peak that was fractionated and subsequently injected into the liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) system. The MRM (Multiple Reaction Monitoring) chromatograms characterized the peak with molecular mass corresponding to an acyclovir-lactose Maillard reaction product. The presence of lactose in commercial tablets was checked using a new TLC method. Overall, the incompatibility of acyclovir with lactose was successfully evaluated using a combination of thermal methods and LC-MS/MS.     

亲水性稀释剂对芦丁降解动力学的影响

目的:研究3种常用亲水性稀释剂在固态和溶液状态下对芦丁降解动力学的影响。方法:将芦丁分别与亲水性稀释剂配伍,制成溶液态或固态的混合物,在40、60℃下定时取样并测定芦丁含量,用降解动力学方程对不同芦丁溶液的浓度-时间数据进行拟合。结果:在固态下,使用乳糖或混合稀释剂可显著提高芦丁稳定性,但甘露醇和蔗糖与芦丁配伍加速了药物的降解;在溶液状态下,3种辅料的加入均提高了芦丁的稳定性,大部分溶液的降解过程符合一级动力学方程。结论:在固态和溶液状态下,亲水性辅料对芦丁稳定性有不同的影响。     

护理干预对母婴分离产妇乳汁分泌的影响

目的 探讨护理干预对母婴分离产妇乳汁分泌的影响.方法 选取母婴分离产妇160例,将其按照随机数字表法分为研究组和对照组各80例,对照组采用常规护理,研究组采用乳房护理干预,比较两组产妇产后开始泌乳时间、泌乳量及乳房肿胀发生率.结果 研究组产妇产后开始泌乳时间早于对照组,第1、2、3、4天的泌乳量均多于对照组,差异有统计学意义（P＜0.05）.产后4d内研究组乳房肿胀发生率为13.75％,低于对照组的35.00％,差异有统计学意义（x^2=6.132,P＜0.05）.两组均随访1个月,研究组母乳喂养率为85.00％,高于对照组的66.25％,差异有统计学意义（x^2=4.120,P＜0.05）.结论 乳房护理干预可加快母婴分离产妇的泌乳时间,增加乳汁分泌量,减轻乳房肿胀,保证母乳的顺利喂养.     

冬葵滋乳汤治疗缺乳症的临床观察

目的：分析冬葵滋乳汤治疗缺乳症的临床效果。方法研究我院产科住院出现的96例缺乳症患者，按照治疗方法不同划分为两组，对照组40例患者采用传统按摩方法，观察组56例患者采用按摩结合冬葵滋乳汤治疗，比较分析不同方法的治疗效果。结果观察组患者的治疗有效率为89.3%，对照组患者的治疗有效率为72.5%，观察组患者的治疗有效率明显优于对照组，差异有统计学意义（P＜0.05）。结论产妇缺乳情况临床比较常见，在按摩乳房基础上结合采用冬葵滋乳汤治疗，可刺激乳汁分泌，疗效显著。     

检测黄热病减毒活疫苗中乳糖和山梨糖醇含量的HPLC的建立

目的  建立检测黄热病减毒活疫苗中乳糖和山梨糖醇含量的高效液相色谱法（high performance liquid chromatography,HPLC）,并验证该法。方法  建立的HPLC的色谱条件确定为：离子排斥色谱柱 Aminex^® HPX-87H （300 mm×7.8 mm）,流动相0.004 mol/L硫酸、流速0.8 ml/min、柱温50 ℃,进样量20 µl。检测该法的系统适用性,并验证该法的线性、准确度、精密度、专属性、稳定性和耐用性。结果  该法的乳糖与山梨糖醇峰间的分离度为6.68,乳糖和山梨糖醇标准曲线的线性良好,线性的决定系数分别为0.999 98和0.999 87。该法的准确度良好,乳糖和山梨糖醇的回收率分别为100.2%～100.4%和101.0%～101.7%,均符合规定的要求。 6次重复检测的乳糖和山梨糖醇结果相对标准偏差分别为0.00%和0.08%;2名分析员于不同时间检测12次的乳糖和山梨糖醇结果相对标准偏差分别为0.30%和0.99%。该法检测乳糖和山梨糖醇质量浓度的定量限分别为0.05 mg/ml和0.06mg/ml。结论  建立的HPLC可用于检测黄热病减毒活疫苗中的乳糖和山梨糖醇含量。     

硫酸软骨素裂解酶发酵培养基的获得及发酵条件的优化

目的考察发酵培养基中碳源、氮源及无机盐等因素及各种发酵条件对温和气单孢菌YH311产硫酸软骨素裂解酶的影响,获得硫酸软骨素裂解酶最佳发酵培养基和发酵条件。方法采用单因素实验法、均匀设计法及正交设计法。结果获得的最优培养基配方(g·L-1)为:葡萄糖2 5 ,牛肉膏5 0 0 ,硫酸软骨素10 0 ,尿素0 5 ,MgSO4·7H2 O 9 0 ( pH 7 0 ) ;最适产酶条件为:2 % ( φ)种子液,2 8℃,2 0 0r·min-1,振荡通气培养2 4h。在优化条件下,硫酸软骨素裂解酶的产率可达110 0 0U·L-1。结论通过对发酵培养基及发酵条件的优化可将硫酸软骨素裂解酶的产量提高5倍。     

Calorimetric determination of amorphous content in lactose: a note on the preparation of calibration curves

Calorimetric methods (isothermal or solution calorimetry) offer the ability to detect amorphous contents to 0.5% (w/w) or better in processed pharmaceuticals and calorimetric data are becoming more widely accepted in regulatory submissions. However, both methods require the construction of calibration curves, prepared using quantitative physical mixtures of entirely amorphous and entirely crystalline material. If the sample under investigation exists in two or more isomers or polymorphs, and the enthalpy of solution (solution calorimetry) or the enthalpy of crystallisation (isothermal calorimetry) are different for the isomers or polymorphs, then it must be ensured that the batch of material used to prepare the calibration samples has the same isomeric or polymorphic composition as the (processed) material to be tested. Here, we demonstrate the problems that may arise using lactose as a pharmaceutically important model substance. Calibration curves were prepared from solution calorimetry and isothermal gas perfusion calorimetry data using two batches of lactose (one predominantly anhydrous -lactose and one predominantly β-lactose). The calibration curves are shown to be significantly different for the two batches, and it is shown that quantification of the amorphous content of a processed sample of unknown isomeric composition is impossible, unless the calibration curve is prepared from the same batch of material as the processed sample. In addition, some of the other problems inherent in using isothermal gas perfusion calorimetry for amorphous content determination, such as wetting issues and the preparation of calibration standards that mimic processes samples, are discussed.