高压蒸汽灭菌柜性能验证方法的研究

高压蒸汽灭菌柜在使用之前和运行一定时间后,必须进行性能验证,采用热分布,热穿透和微生物挑战试验法对GE,GEV型脉冲式蒸汽灭菌柜的性能进行验证,多孔物质及流体物质灭菌循环中,灭菌腔内不存在冷点,具备有效的热穿透力,嗜热脂肪芽孢杆菌（ATCC7953）在规定灭菌时间内被完全杀死。因而确认高压灭菌柜的各项性能均达到生产要求,由此建立的一套验证方案及试验方法和结果得到了国家GMP认证中心的认可。     

临床口腔器械灭菌方法比较

目的:对比压力蒸汽灭菌与化学灭菌剂两种灭菌方法对临床口腔器械的灭菌效果。方法:以金黄色葡萄球菌、白色念珠菌种制备菌悬液,采用悬液定性法进行灭菌实验,以无菌检查法检查口腔器械灭菌效果。结果:有效氯含量2000mg/L的含氯灭菌剂和2%的碱性戊二醛作用一段时间后都不能使手机、吸唾器全部达到无菌;采用135℃的压力蒸汽灭菌10分钟可以使手机、吸唾器全部灭菌。结论:压力蒸汽灭菌比化学灭菌更为可靠,灭活TTV,HBs Ag的效果更好。     

高温灭菌操作中常见错误的分析

高温灭菌是指用热能杀死微生物。其原理是高温使原生质中的蛋白质变性、使酶失活,致使微生物死亡。高温灭菌主要有高压蒸汽灭菌法、干热灭菌法和灼烧灭菌法几种。如果操作不当,即达不到预期的灭菌效果。现就常见错误分析如下。1高压蒸汽灭菌蒸汽灭菌属湿热灭菌,由于湿热灭菌有潜能存在,被灭菌物体的温度比蒸汽的低,蒸汽在其表面凝结成水,放出潜能,可迅速提高被灭菌物体的温度。又由于水和水蒸汽比空气的热容量大、导热快、穿透力强,所以,与干热灭菌相比,灭菌需要的温度低、时间短。由于高压蒸汽灭菌法水蒸汽的温度随其所受压力的…     

探讨热原试验中影响试验数据的因素

目的通过几组试验,分析热原试验中存在常见影响试验数据的几个要素,并提出解决建议。方法对供试品、预选周期、基础体温、家兔的休息周期等多个方面进行统计,总结影响热原数据变化因素。结果家兔升温总和均值随着连续注射批次的增加而有所降低,体温灵敏度变差;合格家兔在4周以内再次预选,合格比例85%以上,6周符合要求的比例为79.1%,9周合格比例降至66.6%;基础体温38.0~38.4℃及39.3~39.6℃区间家兔实验中体温波动幅度≥0.6℃的动物例数较多,38.0~38.4℃区间家兔降温0℃动物数达到50.0%,39.3~39.6℃区间家兔最大升温≥0.4℃的动物数比例较高;家兔冬季基础体温略低于夏季(约0.2℃),休息72~96 h后对家兔基础体温均值、异常体温动物的数量有较好的控制。结论热原检查应尽量采用不同品种供试品交替试验,并通过控制预选兔的使用周期及合理安排家兔实验休息周期,选择基础体温适中的家兔进行试验,以保证热原试验数据的准确性。     

浙江省热原检查用兔敏感性状况调查

目的调查浙江省热原检查用兔对细菌内毒素的敏感性情况,为提高热原检查结果的准确性和可靠性提供参考。方法对全省所有取得生产许可证单位的家兔,用国家颁发的细菌内毒素标准品,＂热原检查法＂进行检查,剂量分别为5EU/Kg和10EU/Kg,记录并比较各单位家兔的平均升温值和升温率。结果对细菌内毒素,各兔场家兔的敏感性有一定的差异。静脉注射5EU/kg,平均升温值为0.40℃～0.87℃,升温率为35%～83%;静脉注射10EU/kg,平均升温值为0.74℃～1.16℃,升温率为70%～94%。结论不同生产单位的家兔对细菌内毒素的敏感性不同,有必要对热原检查用家兔进行细菌内毒素敏感性检查。     

影响家兔热原检查结果的因素分析

目的统计实验数据,分析影响家兔热原检查结果的因素。方法将一定剂量的供试品静脉注入家兔体内,在规定时间内,观察家兔体温升高的情况。结果基础体温≥38.9℃的家兔,其升温≥0.4℃及≥0.6℃的百分比与基础体温<38.9℃家兔相比具有显著性差异(P<0.05),且不同季节家兔升温≥0.4℃的家兔数百分比具有显著性差异(P<0.05),夏秋两季所占百分数高于冬春两季,夏季(6～8月)家兔基础体温较高。结论不同基础体温家兔对热原敏感程度不同,敏感性随家兔基础体温的升高而下降,为保证热原试验结果的准确性,夏季应适当提前热原质检查时间。     

生化药物生产过程中控制热原的方法

热原是微生物的代谢产物 ,是微生物的一种内毒素 ,其主要成分是脂多糖 ,分子量一般为 10 6左右。去除热原的主要方法有 :1 高温法。多在 2 5 0℃加热 30分钟以上。2 酸碱法。用酸或碱进行处理 ,破坏热原。3 吸附法。常用 0 1%～ 0 5 %的活性炭吸附处理。4 层析法。利用离子交换树脂或分子筛凝胶层析处理。5 超滤法。使用超滤装置滤除热原物质。为了保证热原符合规定 ,往往要经过多次实验才能选择合适的方法 ,设计出适宜的...     

细菌内毒素检测法在注射用肝复肽检测中的应用

通过对注射用肝复肽稀释后,采用细菌内毒素试验对其进行检测,并与家兔热原试验相比较。结果表明,细菌内毒素试验可以替代家兔热原试验用于注射用肝复肽的检测。     

不同基础体温的家兔对热原检查结果的影响

对实验中使用的普通级家兔基础体温进行统计,观察不同基础体温家兔注射血液制品后的升温情况。按照中华人民共和国药典(2005)年版三部的热原检查规定进行测定,将实验家兔基础体温38.0℃~39.6℃分为3组:38.0℃~38.5℃为1组;38.6℃~39.0℃为2组;39.1℃~39.6℃为3组。注射制品后,家兔升温≥0.4℃记为升温家兔,统计升温≥0.4℃的家兔升温百分率并对其进行统计学处理。经卡方检验,升温家兔≥0.4℃的百分率1组与2组、1组与3组有显著性差异(p<0.05);2组与3组无显著性差异(p>0.05)。家兔对热原的敏感性随基础体温的高低而有明显的差异,基础体温偏低的家兔对热原更敏感,其升温幅度大于基础体温偏高的家兔。     

对不同材料包扎的生产用容器灭菌效果的比较试验

为了改进长期以来细胞瓶以牛皮纸加无纺布包装后进行灭菌的方式,实验中依据国内外的有关资料和现行GMP的要求,结合生产的实际情况,以15L细胞瓶为对象,用不同材料(牛皮纸加无纺布、铝箔纸、两层无纺布、带砂芯的硅胶塞)包装后进行灭菌效果的比较试验及残留蒸汽冷凝水测量试验,结果显示用带砂芯的硅胶塞包装的细胞瓶在灭菌过程中瓶内实际温度均能达到设定要求,热穿透及微生物标的验证试验也符合《中华人民共和国药典》(三部)2005年版的标准要求,残留蒸汽冷凝水明显少于其它包装方式,有最好的实际应用价值。     

Graphical Procedure for Comparing Thermal Death of Bacillus stearothermophilus Spores in Saturated and Superheated Steam

The thermal death curve of dried spores of Bacillus stearothermophilus in saturated steam was characterized by three phases: (i) a sharp initial rise in viable count; (ii) a low rate of death which gradually increased; and (iii) logarithmic death at maximal rate. The first phase was a reflection of inadequate heat activation of the spore population. The second and third phases represented the characteristic thermal death curve of the spores in saturated steam. A jacketed steam sterilizer, equipped with a system for initial evacuation of the chamber, was examined for superheat during normal operation. Measurements of spore inactivation and temperature revealed superheat in surface layers of fabrics being processed in steam at 121 C. The high temperature of the fabric surfaces was attributed to absorption of excess heat energy from superheated steam. The superheated steam was produced at the beginning of the normal sterilizing cycle by transfer of heat from the steam-heated jacket to saturated steam entering the vessel.     

Life cycle assessment of a detailed dairy processing model and recommendations for the allocation to single products

Purpose

This study analyses the environmental impacts referring to dairy products and to the operation of a dairy. The study aims to better understand different process stages in a dairy operation. This analysis can be used to improve the flows of energy, water, and materials in the dairy operation. The results are also used to suggest an improved allocation model for assigning the impacts of operation to single dairy products.

Methods

The analysis is based on a detailed, product-specific model calculation for the use of energy, water, and chemicals for more than 40 subprocesses of a dairy operation. This model has been used to elaborate the life cycle inventory for a detailed life cycle assessment study. The environmental impacts are analyzed from cradle to gate including and excluding the raw milk input. The environmental impacts are assessed with the midpoint indicators suggested by the International Reference Life Cycle Data System. Finally, results of this study are compared with an allocation model recommended for life cycle assessment (LCA) studies on milk products.

Results and discussion

The analysis of the model dairy shows that raw milk production has the main impact in all categories. Consumer packaging has the second biggest impact in many categories. The detailed dairy processing model allows the assignment of inputs and outputs for each subprocess to single dairy products and thus avoids allocation largely. The analysis of inputs to different dairy products per kilogram shows that ultra-high-temperature (UHT)-processed milk uses more chemicals for cleaning compared to the other products. Cream uses more electricity and heat compared to UHT milk and to yogurt.

Conclusions

A detailed discussion shows the overlaps and differences found for the allocation of inputs to the milk processing to final dairy products. Allocation models for different types of inputs are partly confirmed by the detailed theoretical model used for this LCA. The allocation of chemicals, steam, and electricity to single products can be improved based on the detailed dairy model developed in this study.

     

Modeling transport processes in sterilization-in-place.

SIP (sterilization-in-place) of equipment using saturated steam is limited by transport processes that restrict the distribution of sterilizing steam. The following are two crucial operations: the removal of air prior to sterilization, and the removal of condensate during the sterilization. Using simple model systems of pipes and tanks, characteristic operating parameters were examined and steady-state models were analyzed. The results were used to evaluate design aspects of SIP, including heat insulation, spacing of steam traps, sloping of lines, steam velocities and consumption, placement of temperature sensors, and scale factors in piping. A more reliable SIP design is achievable by insulating equipment, spacing steam traps to limit condensate buildup, providing an effective air removal operation, and providing reliable, high-quality steam.     

Selective killing of transformed rat cells by minute virus of mice does not require infectious virus production.

Fischer rat fibroblasts, naturally resistant to killing by the fibrotropic strain of minute virus of mice [(parvovirus MVM(p)], became sensitive to MVM when transformed by polyomavirus. This sensitization did not involve an increase in the percentage of cells which synthesized viral capsid antigens or in the percentage of cells which produced infectious virus. The addition of anti-MVM antiserum to the growth medium of MVM-infected cells had only a small effect on their survival rates, indicating that the majority of the killing effect of MVM occurs in a single cycle of infection. The data indicate that cell killing by MVM is independent of infectious virus production and thus support the notion that the preferential cytolytic effect is affected by viral cytotoxic gene products which accumulate to intolerable levels in transformed cells but not in normal ones. Finally, using cells transformed with polyomavirus and genomic and subgenomic clones of polyomavirus, we showed that the extent of sensitization to killing by MVM depended on the transforming agent used.     

Production of citric acid from n-paraffins bySaccharomycopsis lipolytica: Kinetics and balance of the fermentation

Summary The excretion of citric and isocitric acids was studied in a stirred fermentor with control of various fermentation parameters. Growth being nitrogen-limited, excretion was found to start at the end of the growth phase, constant production rates being then obtained for the two acids for about 90 h. A linear relationship between these production rates and cell density is observed, thus allowing a definition of specific production rates. Variation of these rates with temperature, aeration, pH and medium iron content were studied. The main effects observed are those of pH, which shows a clear optimum at pH 5, and of iron content, the lower values of which promote citric acid excretion. During the excretion phase rate measurements for all reactants (n-paraffins-oxygen) and products (carbon dioxide-citric and isocitric acids) show that good carbon and oxygen balance are obtained. Comparison with a similar fermentation using glucose is also presented and discussed.Abbreviations v.v.m. volume of air per volume of medium per minute - st.p.m. strokes per minute This work is a part of a Doctorat de Spécialité thesis submitted by R. Marchal to the University of Nancy 24-7-1975     

影响生物制品冻干粉针剂水分的探讨

探讨生物制品冻干粉针剂样品放置一时间后残余水分增高的原因。进行了水分测定,真空度检测,二甲硅油和丁基橡胶药用瓶塞干燥失重的检测。冻干后每只丁基橡胶药用瓶塞平均含水分0.00224g。结果表明丁基橡胶药用瓶塞灭苗,干燥和冻干过程中去除水分不彻底是引起样品中水分升高的直接原因。     

The Proliferative Status of Microcolony-Forming Cells In Mouse Small Intestine

Abstract The technique of thymidine (TdR) suicide has been used with the intestinal microcolony assay to demonstrate that in the middle of the light cycle, nearly all intestinal clonogenic cells, in the B6D2F₁ mice used in these experiments, were not in S phase. Doses of tritiated thymidine [³H]TdR up to 1 mCi/mouse did not kill a significant fraction of those clonogenic cells which survived a test dose of 12 Gy γ-rays. This finding supports some data in the literature, but conflicts with others. However, the suicide technique was found in the studies reported here to be very efficient in sterilizing clonogenic cells in the middle of the dark cycle, and also in a regenerating epithelium at day 3 after a dose of 9 Gy. This implies that the technique can discriminate well between populations of clonogenic cells which differ in their content of cells in S phase. the lack of a suicide effect in the middle of the light cycle indicates that the majority of proliferative epithelial cells are not clonogenic.     

辐照保藏豆制品的研究

豆制品用聚乙烯复合袋分装后,经4kGy、6kGy、8kGy、10kGy的^60Co γ-射线辐照,分别在5℃、25℃条件下贮藏,定期对其进行微生物、感官及营养成分指标检测。经检测分析,豆制品在一定剂量范围内辐照,效果良好,无异味,降低了微生物数量,对营养品质无不良影响,延长了货架期。研究结果表明,用6kGy～8kGy的剂量的γ射线辐照保藏豆制品效果最佳。