白及胶提取工艺的优选

目的探讨白及胶最佳的工艺;方法通过正交试验以水提取物得率为指标,考察提取前冷浸时间、加水总量、煎煮次数、煎煮时间对提取效果的影响;以白及胶得率为指标,考察醇沉时白及水提浓缩液的浓度(药材重量/药液体积)、白及水提浓缩液的含醇量对出胶率的影响.结果白及胶最佳提取工艺是提取前冷浸1 h、加水总量是26倍、煎煮次数2次、煎煮总时间4h;醇沉时白及水提浓缩液的浓度为1:5(W/V)、白及水提浓缩液的含醇量达70%.结论该提取工艺条件科学,白及胶得率高.     

正交试验法优选养血扶正颗粒醇提部分的工艺研究

目的:正交试验法优选养血扶正颗粒的乙醇提取工艺。方法:以浸膏得率及淫羊藿苷的含量作为考核指标,通过L9 (34)正交试验设计比较醇提与醇提水沉的提取工艺条件,确定养血扶正颗粒的最佳醇提工艺。结果:醇提水沉提取工艺影响因素大小依次是:浸渍时间(C)>乙醇浓度(D)>加醇量(A)>浸渍次数(B),最佳提取工艺为处方药材加10倍量乙醇,浸渍提取1次,每次5 d,乙醇浓度65%。结论:醇提水沉淀后浸膏得率及淫羊藿苷的含量有所降低,醇提法优于醇提水沉法,该提取方法合理、可行,为养血扶正颗粒醇提工艺提供了实验依据。     

正交试验法优选醒脑益智颗粒的醇提工艺

目的:通过正交试验优选醒脑益智颗粒的醇提工艺。方法:以丹参总酮及浸膏量为考察指标,通过L9(34)正交试验设计优选醇提工艺条件,确定醒脑益智颗粒的最佳醇提工艺。结果:影响醇提工艺的因素次序为:提取时间(B)>乙醇浓度(A)>提取次数(C)>加醇倍量(D),最佳制备工艺条件为A3B3C2D2,即处方药材加10倍量85%乙醇,浸渍提取2次,每次9d。结论:该制备工艺合理可行,有效成分提取率高。     

正交分析法优化开郁胶囊中芍药苷的提取工艺

目的优选开郁胶囊中有效成分芍药苷的醇提工艺条件.方法采用正交试验方法,对影响芍药苷醇提工艺的药材煎煮次数、乙醇用量、煎煮时间、醇提浓度等因素和不同水平进行考核.应用高效液相色谱法(HPLC)测定不同条件下芍药苷的转移率.结果最优工艺为采用12倍量的60%乙醇加热回流提取3次,每次1 h.结论以上条件为开郁胶囊醇提的最佳工艺,可为开郁胶囊的工业化生产提供理论依据.     

降压益肾颗粒的提取工艺考察

目的：对降压益肾颗粒提取工艺进行优选。方法：采用正交试验法，以总黄酮含量和浸膏收率为指标，考察加水量、浸泡时间、煎煮时间和煎煮次数4因素及醇沉浓度对浸膏收率和有效成分的影响。结果：优化的提取工艺为用药材10倍量水，浸泡1h，每次煎煮1．5h，煎煮3次，醇沉浓度70％。结论：此工艺有效成分提取率高，重现性好，稳定可行。     

正交试验法优选肺炎颗粒水提取工艺

目的: 优选肺炎颗粒水提取的工艺条件.方法: 以干浸膏得率和盐酸麻黄碱含量为指标,采用正交试验法考察不同因素和水平对水煎煮工艺的影响.结果: 影响工艺的次序为煎煮时间＞煎煮次数＞浓缩程度＞醇沉浓度.结论: 优选工艺为:煎煮2次,每次2 h,浓缩到每 ml含 1.5 g生药,醇沉浓度为60%.     

正交试验优选地补更年安颗粒中五味子药材的醇提工艺

目的:优选地补更年安颗粒中五味子药材的醇提工艺。方法:以乙醇浓度、溶媒用量、提取时间为考察因素,以五味子醇甲含量和浸膏得率的综合评分为评价指标,采用正交试验优选制剂中五味子药材醇提最佳工艺。结果:最佳醇提工艺为五味子加10倍量95%乙醇回流提取3h。结论:优选工艺简单、可行,可为该制剂的后续研究提供理论依据。     

加强中药浸膏生产质量管理之管见

《中国药典》一九八五年版一部的制剂通则中载有中药煎膏剂、流浸膏剂(1:1醇提物)、浸膏剂(1:2～5醇提物)三种剂型.这三种制剂可直接作为药品生产、销售.此外,还有一种中药浸膏,是中西药品制剂的初级产品.许多药厂为降低药材运输费用,减少厂区占地面积和环境污染,在外地加工订购中药浸膏.有些药厂或未获《药品生产企业许可证》的浸膏加工厂将生产的中药浸膏直接出售给中成药厂.这些自产自销或委托加工的浸膏,多数无质量标准,有的照订购单位提供的提取浓缩工艺和自拟的内控标准进行加工,其中包括含毒性药材和贵细药材的复方半成品浸膏.     

正交试验优选排石颗粒的提取工艺

目的:优选排石颗粒的提取工艺。方法:以总黄酮含量为指标,以煎煮时间、煎煮次数、加水量、醇提用量为考察因素,应用L9(34)正交试验筛选排石颗粒的最佳提取工艺条件。结果:最佳提取工艺条件为加12倍药材量水,煎煮120min,煎煮3次,干燥、粉碎,再用40倍药材量60%乙醇回流提取3次,每次30min,趁热过滤,回收乙醇。所得浸膏得率和总黄酮含量均较高,且重现性好。结论:优选得到的提取工艺稳定、可行。     

正交试验优选消症贴膏提取工艺

目的:优选消症贴膏中处方药材的提取工艺。方法:以水提醇沉法提取精制,以水苏碱含量和干浸膏得率为评价指标,通过正交试验优选合理的提取工艺参数。结果:优选的消症贴膏最佳水提工艺为醇沉浓度45%,加12倍量水煎煮3次,每次90min。结论:通过直观分析可以确定提取工艺条件;制剂制备工艺可行。     

复方硫洗剂中硫的含量测定

目的研究复方硫洗剂中硫的含量测定.方法采用紫外分光光度法.取硫(升华硫)约0.1 g,加氢氧化钾-稀乙醇(1→10)溶液10 mL,于80 ℃水浴中加热溶解,用水制成1 mL含硫约100 μg的溶液,在(370±2)nm波长处测定.结果硫在60～120 μg·mL-1线性关系良好(r=0.999 5),平均回收率为101.0%(n=4),RSD为1.04%.结论紫外分光光度法测定复方硫洗剂中硫的含量结果较满意.     

硫磺熏蒸对山药中二氧化硫含量的影响

目的探讨硫磺熏蒸对山药中二氧化硫含量的影响。方法选择硫磺用量、熏蒸时间、熏蒸次数3个因素,用L9(34)正交表,用酸蒸馏碘滴定法测定不同熏蒸工艺山药中二氧化硫含量。结果硫磺用量、熏蒸时间对二氧化硫含量影响较大。结论硫磺熏蒸会大大增加山药中二氧化硫残留量,应选择能保证药材质量及用药安全的新的加工工艺。     

Hypothermia reduces sulphur mustard toxicity

The effect of temperature on the development of sulphur mustard (HD)-induced toxicity was investigated in first passage cultures of human skin keratinocytes and on hairless guinea pig skin. When cells exposed to HD were incubated at 37 degrees C, a concentration-dependent decline in viability was observed that was maximal by 2 days. In contrast, no significant HD-induced toxicity was evident up to 4 days posttreatment when the cells were incubated at 25 degrees C. However, these protective effects were lost by 24 h when the cells were switched back to 37 degrees C. The protective effects of hypothermia were also demonstrated when apoptotic endpoints were examined. The HD concentration-dependent induction of fragmented DNA (as quantitated using soluble DNA and the TUNEL reaction), morphology, and p53 expression were all significantly depressed when cell cultures were incubated at 25 degrees C compared to 37 degrees C. When animals were exposed to HD vapour for 2, 4, and 6 min and left at room temperature, lesions were produced whose severity was dependent on exposure time and that were maximal by 72 h posttreatment. Moderate cooling (5-10 degrees C) of HD exposure sites posttreatment (4-6 h) significantly reduced the severity of the resultant lesions. However, in contrast to the in vitro results, these effects were permanent. It appears that the early and noninvasive act of cooling HD-exposed skin may provide a facile means of reducing the severity of HD-induced cutaneous lesions.     

硫磺熏制对山药中二氧化硫残留量的影响

目的考察硫磺熏制对山药中二氧化硫残留量的影响。方法加盐酸使山药中的含硫成分生成二氧化硫,以加有淀粉指示剂的水为吸收液,用碘滴定法测定二氧化硫的残留量。结果没有用硫磺熏制的山药二氧化硫的残留量为0,随着硫磺熏制时用硫量的增加,二氧化硫的残留量也相应增加;若延长摈置时间,其残留量略有降低。民间常用硫磺量熏制出来的怀山药及市售硫熏过的怀山药与其他省份的市售山药相比,二氧化硫的残留量显著低于其他省份。结论传统的硫黄熏制的山药产地加工方法确能导致二氧化硫较多的残留,因此,在保证二氧化硫残留量在一定范围之内的前提下,传统的产地加工方法急待改进。此方法可用于山药中二氧化硫的残留量测定。     

Ionic dependence of sulphur mustard cytotoxicity

The effect of ionic environment on sulphur mustard (bis 2-chloroethyl sulphide; HD) toxicity was examined in CHO-K1 cells. Cultures were treated with HD in different ionic environments at constant osmolar conditions (320 mOsM, pH 7.4). The cultures were refed with fresh culture medium 1 h after HD exposure, and viability was assessed. Little toxicity was apparent when HD exposures were carried out in ion-free sucrose buffer compared to LC₅₀ values of ~ 100-150 μM when the cultures were treated with HD in culture medium. Addition of NaCl to the buffer increased HD toxicity in a salt concentration-dependent manner to values similar to those obtained in culture medium. HD toxicity was dependent on both cationic and anionic species with anionic environment playing a much larger role in determining toxicity. Substitution of NaI for NaCl in the treatment buffers increased HD toxicity by over 1000%. The activity of the sodium hydrogen exchanger (NHE) in recovering from cytosolic acidification in salt-free and in different chloride salts did not correlate with the HD-induced toxicity in these buffers. However, the inhibition by HD of intracellular pH regulation correlated with its toxicity in NaCl, NaI and sucrose buffers. Analytical chemical studies and the toxicity of the iodine mustard derivative ruled out the role of chemical reactions yielding differentially toxic species as being responsible for the differences in HD toxicity observed. This work demonstrates that the early events that HD sets into motion to cause toxicity are dependent on ionic environment, possibly due to intracellular pH deregulation.     

Medical aspects of sulphur mustard poisoning

Sulphur mustard is one of the major chemical warfare agents developed and used during World War I. Large stockpiles are still present in several countries. It is relatively easy to produce and might be used as a terroristic weapon. Sulphur mustard is a vesicant agent and causes cutaneous blisters, respiratory tract damage, eye lesions and bone marrow depression. The clinical picture of poisoning is well known from the thousands of victims during World War I and the Iran-Iraq war. In the latter conflict, sulphur mustard was heavily used and until now about 30,000 victims still suffer from late effects of the agent like chronic obstructive lung disease, lung fibrosis, recurrent corneal ulcer disease, chronic conjunctivitis, abnormal pigmentation of the skin, and several forms of cancer. Despite enormous research efforts during the last 90 years, no specific sulphur mustard antidote has been found. The prospering knowledge and developments of modern medicine created nowadays new chances to minimize sulphur mustard-induced organ damage and late effects.     

pH-dependent toxicity of sulphur mustard in vitro

The dependence of sulphur mustard (HD) toxicity on intracellular (pH(i)) and extracellular pH was examined in CHO-K1 cells. HD produced an immediate and significant concentration-dependent decline in cytosolic pH, and also inhibited the mechanisms responsible for restoring pH(i) to physiological values. The concentration-response of HD-induced cytosolic acidification, closely paralleled the acidification of the extracellular buffer through HD hydrolysis. A viability study was carried out in order to assess the importance of HD-induced cytosolic acidification. Cultures were exposed to HD for 1 h in media that were adjusted through a pH range (pH 5.0-10), and the 24 h LC(50) values were assessed using the viability indicator dye alamarBlue. The toxicity of HD was found to be dependent on extracellular pH, with a greater than eight-fold increase in LD(50) obtained in cultures treated with HD at pH 9.5, compared to those treated at pH 5.0. Assays of apoptotic cell death, including morphology, soluble DNA, caspase-3 activity and TUNEL also showed that as pH was increased, much greater HD concentrations were required to cause cell death. The modest decline in HD half-life measured in buffers of increasing pH, did not account for the protective effects of basic pH. The early event(s) that HD initiates to eventually culminate in cell death are not known. However, based on the data obtained in this study, we propose that HD causes an extracellular acidification through chemical hydrolysis and that this, in both a concentration and temporally related fashion, results in cytosolic acidification. Furthermore, HD also acts to poison the antiporter systems responsible for maintaining physiological pH(i), so that the cells are unable to recover from this insult. It is this irreversible decline in pH(i) that initiates the cascade of events that results in HD-induced cell death.     

The skin reservoir of sulphur mustard.

Studies of the percutaneous reservoir of sulphur mustard (HD) formed during absorption carried out during WWI and WWII are inconclusive. More recent studies have indicated that a significant amount of unreacted HD remains in human epidermal membranes during percutaneous penetration studies in vitro. The present study investigated the nature and persistence of the HD reservoir formed during in vitro penetration studies using dermatomed slices of human and pig skin (0.5mm thick). Amounts of (14)C-HD that (a) penetrated, (b) remained on the surface, (c) were extractable from and (d) remained in the skin after extraction were estimated by liquid scintillation counting (confirmed using GC-MS analysis). The results demonstrated that there is a reservoir of HD in human and pig skin for up to 24h after contamination of the skin surface in vitro with liquid agent. At least some of this reservoir could be extracted with acetonitrile, and the amounts of extracted and unextracted HD exceed the amount required to produce injury in vivo by at least 20 fold. The study demonstrated the presence of a reservoir whether the skin was covered (occluded) or left open to the air (unoccluded). The study concluded that the extractable reservoir was significant in terms of the amount of HD required to induce a vesicant response in human skin. The extractable reservoir was at least 20 times the amount required per cm(2) estimated to cause a response in all of the human population, as defined by studies carried out in human volunteers during the 1940s.     

Carcinogenesis in rats by cyclic N-nitrosamines containing sulphur

The effects of chronic exposure to three sulphur-containing heterocyclic N-nitrosamines were determined after repeated oral administration to female Fischer 344 rats. Nitrosothiazolidine did not significantly affect the survival of the rats or the incidence of tumours at a total dose of 3.5 mmol. Nitrosodithiazine, an analogue of nitrosothiazolidine which contains an extra sulphur atom inserted between the carbons of its CH2-CH2 moiety, produced only three tumours (two of the nasal mucosa) in a group of 20 rats at a total dose of 1.75 mmol/rat. Nitrosothialdine, the all-cis 2,4,6-trimethyl analogue of nitrosodithiazine, was a potent carcinogen that significantly shortened the lifespan and produced oesophageal tumours in 70% of treated rats as well as numerous tumours of the tongue and liver; this outcome was unexpected because alpha-methyl substitution in other heterocyclic nitrosamines usually reduces or eliminates tumorigenicity. The results extend the data base on the carcinogenic activity of molecules containing both divalent sulphur and the nitrosamino function. The lack of significant carcinogenicity of nitrosothiazolidine in this study suggests that its presence in the human food supply presents a relatively minor risk.