Tween-80的化学组分与其溶血作用的关系

采用体外溶血试验考察,对组成Tween-80的8类化学成分进行致溶血性安全评价.结果显示,它们的致溶血能力有显著差异.聚氧乙烯山梨醇酐(PS)、聚氧乙烯异山梨醇(PI)和聚氧乙烯异山梨醇二油酸酯(PID)在浓度为500 μg/ml时未出现溶血,聚氧乙烯山梨醇酐三油酸酯(PSTri)浓度为300 μg/ml、聚氧乙烯山梨醇酐四油酸酯(PSTetra)浓度为500 μg/ml时可导致溶血,而聚氧乙烯山梨醇酐一油酸酯(PSM)浓度为80 μg/ml、聚氧乙烯山梨醇酐二油酸酯(PSD)浓度为120 μg/ml、聚氧乙烯异山梨醇一油酸酯(PIM)浓度为30 μg/ml时即可导致溶血.提示应控制市售Tween-80中各化学组分的含量,以减少其溶血毒性.     

吐温-80对呋喃西林溶液稳定性的影响

目的考察超声条件下不同浓度吐温-80对呋喃西林的增溶作用,筛选吐温-80的最佳用量,提高呋喃西林溶液的稳定性。方法用超声振荡仪将呋喃西林进一步粉碎成更细小的微粒,加入吐温-80做增溶剂配制呋喃西林溶液,样品置2-8℃的低温环境中冷贮3个月观察稳定性。结果加入0.5%吐温-80制备的呋喃西林溶液析出结晶少于对照品;加入1.0%与2%吐温-80制备的呋喃西林溶液无结晶析出,含量符合规定。结论吐温-80能增加呋喃西林的溶解度,用于呋喃西林溶液的制备能提高制剂稳定性。     

Noradrenergic processes involved in the locomotor effects of ethanol.

Male albino Wistar rats were depleted of forebrain noradrenaline by intracerebral injection of 4 microgram of 6-hydroxydopamine into the noradrenaline bundles in the mesencephalon. The locomotor response was examined in response to intraperitoneal injection of ethanol. The locomotor stimulation by 0.1 g/kg ethanol was not altered by the lesion, whereas the sedation found in response to 1 g/kg in controls failed to occur in the lesioned rats and instead a stimulation was seen.     

吐温－20增敏分光光度法测定硫糖铝中铝的含量

目的：建立测定硫糖铝中铝的新方法。方法在乙酸－乙酸钠缓冲溶液中,吐温－20存在下,铝、铬天青S与溴代十六烷基吡啶反应,反应产物在波长620nm处有最大吸收。结果在实验最适条件下,铝浓度在0～0．20mg? L －1之间存在线性关系（r ＝0．9994）。方法检出限为0．008mg? L －1。 RSD＝0．75％～3．95％。样品加标回收率为97．8％。结论方法应用于硫糖铝中铝的测定,结果满意。     

Tween-80并温热对人膀胱癌EJ/ADM的耐药逆转及作用机制

目的观察Tween-80合并温热对人膀胱癌阿霉素耐药细胞株的逆转作用及其机制。方法采用MTT法进行体外药物逆转实验,免疫细胞化学染色显示处理前后耐药细胞P-糖蛋白表达情况。结果①Tween-80合并41℃温热作用前后,EJ/ADM对抗癌药物阿霉素、丝裂霉素、5-氟尿嘧啶等药物的敏感性显著增加(P<0.01);②Tween-80合并41℃温热能够协同抑制p-gp蛋白的表达。结论Tween-80合并41℃温热对人膀胱癌阿霉素耐药细胞的耐药性有逆转作用,逆转机制与其抑制p-gp蛋白的表达有关。     

Effects of beta-phenylethylamine on locomotor activity,body temperature and ethanol blood concentrations during acute ethanol intoxication

Beta-phenylethylamine (PEA) is an endogenous amine which is metabolised by MAO B. The function of this enzyme is known to be modified by ethanol so we have studied the interactions of PEA with ethanol. Rectal temperatures of rats were determined and animals pretreated with ethanol (2.5 g kg⁻¹ IP) 90 min before PEA 20, 40, 100 mg kg⁻¹ IP). Spontaneous locomotor activity (SLA) was then recorded, for 30 min, temperatures redetermined and blood ethanol levels evaluated. PEA increased SLA but did not alter rectal temperatures, and at 40 mg kg⁻¹ it not only attenuated ethanol hypothermia and blood levels but also modified ethanol hypomotility. The highest dose of PEA (100 mg kg⁻¹) decreased blood ethanol concentration and sedation but did not counteract the hypothermia. Thus PEA increased ethanol clearance, though the underlying mechanism is not totally clear. This finding is discussed in relation to its catecholaminergic and enzyme inducing characteristics.     

中药注射剂增溶辅料吐温-80物理化学性能研究进展

目的为中药注射剂增溶辅料吐温-80的物理化学性能研究提供参考。方法经过大量的文献阅读,总结了吐温-80物理性能、表面活性、稳定性、增溶性的研究资料。结果根据中药注射剂的特征,适宜的吐温-80表面活性和稳定性研究相对较少。结论立足中药注射剂特点,吐温-80的物理化学性能研究有待进一步开展。     

气相色谱法同时测定吐温80中7种脂肪酸亲油基的含量

目的:建立用GC测定吐温80中亲油基含量的方法,为吐温80使用适宜性研究奠定基础.方法:采用GC法,选用DB-1毛细管色谱柱,柱温185℃,进样口温度250℃,检测器温度250℃.结果:吐温80中7种亲油基衍生的脂肪酸甲酯(油酸甲酯、亚油酸甲酯、硬脂酸甲酯、肉豆蔻酸甲酯、棕榈油酸甲酯、棕榈酸甲酯、亚麻酸甲酯)在测定范围...     

Behavioral effects of alpha2 adrenoceptor antagonists and their interactions with ethanol in tests of locomotion,exploration and anxiety in mice

The behavioral effects of two highly selective alpha₂-adrenoceptor antagonists, atipamezole and idazoxan, were investigated in mice using the plusmaze test of anxiety and the holeboard test of directed exploration and locomotor activity. No anxiogenic effect, as assessed by the tendency to enter the closed as opposed to open arms of the plusmaze, was noted for either drug at any dose tested. Neither were there any significant effects on locomotor activity or directed exploration (head-dipping) in the holeboard, or total plusmaze arm entries at any dose of either drug. The co-administration of either atipamezole or idazoxan had no effect on either the anxiolytic effect of ethanol (2 g/kg) or its locomotor stimulant effect in the holeboard. Atipamezole (1.0 and 3.0 mg/kg) significantly reversed the ethanol-induced reduction in exploratory head-dipping; a similar trend was seen for idazoxan. There was also a significant potentiation of the ethanol-induced increase in the number of total arm entries made on the plusmaze caused by 1.0 mg/kg (but not 3.0 mg/kg) atipamezole and both 0.3 and 1.0 mg/kg idazoxan. The results suggest that some of the behavioral effects of ethanol can be reversed by alpha₂-adrenoceptor antagonists whilst others are unchanged.     

The effects of repeated doses of ethanol on exploration and its habituation

The effects of ethanol (0.8–2.4 g/kg) on exploratory behavior and its habituation were investigated by testing DBA/2 mice in a holeboard apparatus. Mice familiar with the holeboard had lower levels of exploration than animals with no previous experience in the apparatus. If the animals received ethanol during their first exposure to the holeboard they did not show the same degree of habituation. Ethanol (0.8 g/kg) increased the exploration of animals naive to the holeboard, but failed significantly to increase the exploration of animals familiar with the apparatus. An increase in locomotor activity was observed following treatment with ethanol (2.4 g/kg). This was potentiated if animals received a single treatment with ethanol 3 days earlier, but only if they were tested in the apparatus following the initial treatment. These results have important implications for the design of experiments investigating tolerance and sensitization to ethanol's effects on locomotor activity and exploration.     

中药注射剂所含吐温-80与过敏反应关系的研究

目的：观察不同浓度吐温-80溶液、吐温-80含量不同的中药注射剂对RBL-2H3细胞脱颗粒的影响,探讨中药注射剂所含吐温-80与过敏反应的关系。方法：体外培养RBL-2H3细胞,加入不同浓度（40、20、10、2、1、0.2、0.1、0.05mg/mL）的吐温-80溶液,之后加中性红染液,计数不同浓度吐温-80溶液各组及对照组的脱颗粒细胞,并计算其百分率,同时检测细胞上清液中β-氨基己糖苷酶及组胺的释放量;测定穿琥宁注射液和香丹注射液中吐温-80的含量,2种中药注射剂对RBL-2H3细胞的半数抑制浓度（IC50）以及加入2种注射液各组细胞释放组胺的量。结果：中性红染色实验显示吐温-80可导致RBL-2H3细胞脱颗粒,表现为肥大细胞体积变大,内有空泡产生;浓度为40、20、10、2、1、0.2、0.1mg/mL的吐温-80溶液各组和RPMI1640对照组导致细胞的脱颗粒百分率分别为（57.38±0.47）、（32.54±2.33）、（21.74±0.72）、（16.96±0.26）、（11.40±1.70）、（9.71±0.26）、（7.22±0.15）和（1.51±1.39）%,2组相比差异有统计学意义（P〈0.05,P〈0.01）;浓度为40、20、2、1、0.2mg/mL的吐温-80溶液各组和RPMI1640对照组致细胞β-氨基己糖苷酶的释放率分别为（52.44±1.53）、（18.91±0.77）、（7.50±1.82）、（6.65±0.20）、（6.15±0.27）和（0.35±0.06）%,2组相比差异有统计学意义（P〈0.05,P〈0.01）;不同浓度吐温-80溶液引起RBL-2H3细胞释放组胺的量也不同;当吐温-80溶液浓度为20～0.1mg/mL时,RBL-2H3细胞脱颗粒百分率、β-氨基己糖苷酶的释放率及其释放组胺的量均与吐温-80溶液的浓度呈线性关系（r=0.9862,r=0.9849,r=0.9740）。穿琥宁注射液和香丹注射液中吐温-80的含量分别为（0.086±0.004）和（0.070±0.008）mg/mL,2种注射液对RBL-2H3细胞的IC50分别为（57.4±1.2）、（1.0±0.2）μL/mL,穿琥宁注射液和香丹注射液组组胺释放量分别为（2.39±0.01）和（1.87±0.00）ng/mL。结论：吐温-80可引起RBL-2H3细胞脱颗粒释放炎症介质;RBL-2H3细胞组胺的释放量与中药注射剂中吐温-80的含量有关;中药注射剂中所含的吐温-80可能与过敏反应的发生有关。     

Apomorphine effects on behavioral response to ethanol in mice selectively bred for differential sensitivity to ethanol

Two lines of mice selectively bred for differences in response to a hypnotic dose of ethanol were administered apomorphine alone or in combination with ethanol. When administered by itself, apomorphine produced similar dose-dependent depression of locomotor activity and increases in stereotypy in the two lines. Doses of apomorphine (0.5 microM/kg and 2 microM/kg) thought to bind only presynaptic dopamine receptors blocked the slight locomotor activation to 1.5 g/kg ethanol in the ethanol-sensitive Long-Sleep (LS) mice; in the ethanol-insensitive Short-Sleep (SS) mice which show marked activation to all subhypnotic doses of ethanol, these doses of apomorphine only attenuated the activation. A higher apomorphine dose (8 microM/kg) antagonized the locomotor depressant effects of 2.0 and 2.5 g/kg of ethanol in LS mice but did not alter the shape of the SS ethanol dose response curve for locomotor activity. Apomorphine (2 and 8 microM/kg) potentiated ethanol-induced loss of the righting reflex in LS mice in a dose dependent fashion, but did not alter this soporific effect of ethanol in SS mice. These findings extend the data base suggesting a role for dopamine both in the mechanism(s) differentiating the LS and SS mice and the stimulant and intoxicating properties of ethanol.     

Tween-80对Peterson法测定多肽含量的影响

目的 研究对Petenon法测定多肽(蛋白质)含量有干扰作用的Tween—80的浓度范围。方法 Peteron法。结果 测定浓度小于0．14％的Tween—80对Peterson法无干扰作用。结论 可以通过控制Tween—80在测定液中的浓度来消除其对Peterson法测定多肽含量的影响。     

Antagonism of the stimulant and depressant effects of ethanol in rats by naloxone

The action of naloxone (0.5 and 2 mg/kg IP) on the behavioural effects of a low (2 g/kg PO) and a high dose (4 g/kg PO) of ethanol was studied in rats. Ethanol at the low dose increased spontaneous motility, enhancing open-field external ambulations and reducing shuttle-box latency. All these effects were antagonized by naloxone. Ethanol at the high dose produced hypomotility, decreasing open-field external ambulations and impairing shuttle-box performance. In this case, naloxone also reduced the ethanol effect, but its action was less consistent. Therefore, although mechanisms other than a specific opioid receptor blockade by naloxone must be considered, an involvement of opioid peptides in the effects of ethanol cannot be discounted.     

Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, Tween-80 and Tween-20

Immunosafety analysis of pharmaceutical surfactants is an important step in understanding the complex mechanisms by which they induce side effects in susceptible patients. This paper provides experimental evidences that polyethoxylated surfactants, Cremophor-EL and Tween-80, also known as Polysorbate-80, activate the complement system in vitro, in normal human serum and plasma. They appeared to be more efficient reactogens than their structural homolog, Tween-20. Cremophor-EL and Tween-80 promoted the generation of biologically active complement products, C3a, C5a and C5b-9. Consistently, Paclitaxel and Taxotere (Docetaxel), pharmaceuticals formulated in Cremophor-EL and Tween-80, activated the complement system in similar extent. Moreover, comparison of serum reactivity against the drug-loaded and drug-free formulations exhibited a significant linear correlation. Taken together, these results are consistent with the hypothesis that therapeutic side effects, such as acute hypersensitivity and systemic immunostimulation, caused by intravenous nanomedicines containing polyethoxylated detergents such as Cremophor-EL and Tween-80, can be attributed to complement activation-derived inflammatory mediators.     

Motor stimulant effects of ethanol and acetaldehyde injected into the posterior ventral tegmental area of rats: role of opioid receptors

Rationale  A recently published study has shown that microinjections of ethanol, or its metabolite, acetaldehyde into the substantia nigra pars reticulata, are able to produce behavioral activation in rats. Another brain site that could participate in such effects is the ventral tegmental area (VTA). Objectives  We have investigated the locomotor-activating effects of local microinjections of ethanol and acetaldehyde into the posterior VTA of rats and the role of opioid receptors in such effects. Materials  Cannulae were placed into the posterior VTA to perform microinjections of ethanol (75 or 150 nmol) or acetaldehyde (25 or 250 nmol) in animals not previously microinjected or microinjected with either the nonselective opioid antagonist naltrexone (13.2 nmol) or the irreversible antagonist of the μ-opioid receptors β-funaltrexamine (β-FNA; 2.5 nmol). After injections, spontaneous activity was monitored for 60 min. Results  Injections of ethanol or acetaldehyde into the VTA increased the locomotor activity of rats with maximal effects at doses of 150 nmol for ethanol and 250 nmol for acetaldehyde. These locomotor-activating effects were reduced by previously administering naltrexone (13.2 nmol) or β-FNA (2.5 nmol) into the VTA. Conclusions  The posterior VTA is another brain region involved in the locomotor activation after the intracerebroventricular administration of ethanol or acetaldehyde. Our data indicate that opioid receptors, particularly the μ-opioid receptors, could be the target of the actions of these compounds in the VTA. These results are consistent with the hypothesis that acetaldehyde could be a mediator of some ethanol effects.     

Parametric analysis of the development and expression of ethanol-induced behavioral sensitization in female Swiss mice: effects of dose,injection schedule,and test context

Rationale  Repeated administrations of ethanol induce a progressive and enduring increase in its locomotor stimulant effects, a phenomenon termed behavioral sensitization that has not been systematically characterized. Objective  The aim of the present studies was to characterize the development and expression of ethanol sensitization in female Swiss mice by examining (1) the doses of ethanol that induce behavioral sensitization, (2) the doses of acute ethanol challenges that are necessary to express behavioral sensitization, (3) the effects of the intervals between administrations, and (4) the context dependency of ethanol sensitization. Materials and methods  Mice were i.p. injected for 8 days with various ethanol doses, and locomotion was recorded for 5 min. Two days after the last sensitization session, ethanol sensitization was tested in 30-min test sessions. Results  Mice repeatedly injected with 2.5 g/kg ethanol showed a progressive (200–300%) increase in locomotor activity. In response to a 2.5 g/kg ethanol challenge, the mice repeatedly treated with doses above 1.5 g/kg showed a significant sensitization. Following the induction of sensitization with the maximally effective sensitizing dose (2.5 g/kg), mice showed greater activation after challenges with 1.5, 2.0, 2.5, and 3.0 g/kg ethanol. The intervals (24, 48, or 96 h) between ethanol injections did not affect the induction or expression of sensitization. Finally, sensitization to 2.5 g/kg ethanol was expressed regardless of the context in which it was induced. Conclusions  Female Swiss mice develop a robust context-independent sensitization after repeated ethanol injections at all doses above 1.5 g/kg, including highly sedative doses such as 4 g/kg.     

Time course of the locomotor stimulant and depressant effects of a single low dose of ethanol in mice

The acute effects of alcohol on spontaneous locomotor activity in male Swiss mice were studied at various times after an IP injection of 2 g/kg ethanol. Subjects were placed alone in a novel arena and videotape recordings were made of behaviour: trials were of 500-s duration and commenced at either 30, 60, 120, or 180 min after alcohol administration. Measures of behaviour included various indices of ambulation and immobility, together with a more detailed ethological analysis of the frequencies of all other acts and postures shown by test animals. Ambulation showed a biphasic response to alcohol treatment, consisting of an initial stimulation followed by a suppression after 3 h. Immobility was also increased by alcohol, and showed peak stimulation in trials commencing 30 min after administration: thereafter there was a progressive return to baseline levels. Many behavioural elements were suppressed including rearing, digging, shaking, and abbreviated grooming. Ethanol thus appeared to produce two distinct types of depression, in terms of increased immobility (and suppression of other behaviour) and in terms of decreased ambulation, the latter occurring when immobility had returned to baseline levels.     

An analysis of some effects of ethanol on performance in a passive avoidance task

In a one-trial step-through passive avoidance task, pretraining administration of ethanol was shown to decrease the latencies to step through at both training (day 1) and testing (day 2) for both rats and mice. A detailed analysis of these effects showed that they differed from those reported previously by others. The mechanisms underlying these effects of ethanol were also examined. The decreased day 1 latency to step through seen in rats may have been caused by an ethanol-induced hypermotility. However, ethanol did not increase the locomotor activity of mice, although it also reduced the day 1 latency to step through of this species. In addition, it was found that the ethanol-induced impairment of passive avoidance responding (i.e. the decreased day 2 latency to step through) was not state-dependent and that it was unlikely that it could be explained by a drug-induced impairment of task acquisition, long-term memory formation or memory recall. It also seemed unlikely that the impairment could be explained by an ethanol-induced decrease in shock sensitivity. Other mechanisms which may be involved are discussed.     

Involvement of endogenous opioid mechanisms in the interaction between stress and ethanol

The involvement of endogenous opioid mechanisms in the interaction between stress and ethanol was investigated in the rat. Animals were pretreated with naltrexone (10 mg/kg) or saline 3 h before a second injection consisting of ethanol (1.0 g/kg) or saline. They were then restrained for 15 or 60 min or left in home cages for an equivalent amount of time. After restraint, animals were either subjected to an open-field test or decapitated to collect blood for corticosterone determinations. Locomotor depression was found to be induced by 15 but not 60 min restraint. In naltrexone-treated animals, however, 60 min restraint was also found to induce locomotor depression. Ethanol pretreatment was found to block the locomotor depression induced by 15 min restraint. Such an interaction was in turn antagonized by naltrexone. In the 15 min condition, stress and ethanol were also found to interact in their effects on plasma levels of corticosterone. Naltrexone did not alter any effects of the stressors on corticosterone levels. These results provide support for the involvement of endogenous opioid mechanisms in the interaction of stress and ethanol at a behavioural level.