穿琥宁对大肠癌HCT-8/5-FU耐药细胞株逆转作用的研究

目的:探讨中药制剂穿琥宁对HCT-8/5-FU多药耐药细胞株的影响.方法:观察0.4,1.2和2.4mg·mL-1穿琥宁作用下的HCT-8/5-FU多药耐药细胞株生长曲线,MTT法检测上述浓度下的细胞抑制率.MTT法、流式细胞仪PI染色法检测穿琥宁与化疗药物5-氟尿嘧啶(5-FU)、顺铂(DDP)和阿霉素(ADM)联合作用下,对HCT-8/5-FU耐药细胞的毒性作用和凋亡率.流式细胞仪罗丹明染色法和PI染色法探讨穿琥宁的作用机制.结果:0.4mg·mL-1穿琥宁生长曲线与正常对照组无明显差别,1.2mg·mL-1穿琥宁对细胞生长有轻度抑制作用,2.4mg·mL-1浓度有一定抑制,但细胞仍可生长.MTT法检测0.4,1.2,2.4mg·mL-1穿琥宁作用下,HCT-8/5-FU耐药细胞株的抑制率分别为7.2%,13.2%,21%.1.2mg·mL-1穿琥宁与5-FU,DDP,AMD联合作用,与这3种化疗药物单独作用比较细胞凋亡率分别为54.2%/26.4%;42.6%/13.6%;30.8%/14.2%,差异显著(P<0.01).罗丹明染色法提示穿琥宁的作用机制可能与影响P-170的活性有关.但穿琥宁本身并不诱导凋亡,对细胞周期也无影响.结论:低浓度穿琥宁对HCT-8/5-FU细胞无明显抑制作用;与5-FU,ADM,DDP联合作用,可增加上述化疗药物的毒性作用,使肿瘤细胞的凋亡率增高,其机制可能与抑制P-170功能有关.     

穿琥宁肠溶胶囊的制备与溶出度研究

目的: 研究穿琥宁肠溶胶囊的制备与溶出度.方法: 通过体外溶出度的测定选择最佳制备条件;采用高效液相色谱法测定主药穿琥宁的含量.结果: 最优处方制备的穿琥宁肠溶胶囊在45 min时的体外溶出度为98.36%;标准曲线线性范围为13～138 μg·ml-1,回归方程为A=20 469.9 25 429.9C(r=0.999 9);平均加样回收率为102.20%.结论: 该制剂制备工艺简单,体外溶出度较好.     

高纯度穿琥宁冻干粉针的动物急性毒性研究

目的:提高穿琥宁冻干粉针质量.方法:采用"高纯度穿琥宁生产工艺"专利技术生产穿琥宁冻干粉针并做动物急性毒性试验与其他厂家同类产品进行比较.结果:用专利技术生产的注射用穿琥宁小鼠静脉注射 LD50明显高于其他厂家生产的同规格产品,单次静脉给药的 LD50达到 910 mg/kg,而国家标准说明书中的 LD50为 675 mg/kg,文献报道穿琥宁注射剂的单次静脉给药的 LD50为 580～ 620 mg/kg.结论:采用专利技术可以大大降低注射用穿琥宁产品的毒性,提高临床安全性.     

穿琥宁药代动力学及绝对生物利用度的实验研究

目的研究穿琥宁经小肠给药后在小鼠体内的药代动力学及绝对生物利用度。方法取小鼠60只,随机分为静脉注射组和小肠给药组。小肠给药组小鼠麻醉后,直接在小肠灌注穿琥宁CMC-Na混悬液,静脉注射组为静脉注射穿琥宁溶液,给药后采用HPLC法测定血药浓度。结果经3p97药动学程序处理,穿琥宁经小肠给药的药—时数据符合二室药代动力学模型,其绝对生物利用度为15.88%。结论小鼠经小肠灌注穿琥宁有一定的生物利用度。     

穿琥宁中空栓的制备及质量控制方法研究

目的:制备穿琥宁中空栓并建立其质量控制方法。方法:以半合成脂肪酸甘油酯为基质,以聚乙二醇300或1,2-丙二醇为分散媒,制备穿琥宁中空栓;采用紫外分光光度法测定主药穿琥宁的含量,测定波长为251nm。结果:穿琥宁检测浓度在6.0～50.0μg.mL-1范围内与吸光度呈良好线性关系(r=0.9999,n=5);2种穿琥宁中空栓的质量考查符合规定。结论:本方法合理、可行。     

注射用穿琥宁沉淀现象的研究

注射用穿琥宁是临床应用疗效较好的一种抗病毒药物,具有解热消炎作用,常用于病毒性肝炎、婴幼儿肺炎、呼吸道感染等病症治疗,在我院小儿科应用较广。临床应用中发现穿琥宁在与10％葡萄糖注射液配伍后有沉淀产生,为此我们通过系列实验对其进行分析研究。1 仪器与药品phs-4型酸度计(杭州亚美电子仪器厂)、注射用穿琥宁(哈尔滨三联药业有限公司)、0.9％氯化钠注射液(本院制剂)、5％葡萄糖注射液(本院制剂)、10％葡萄糖注射液(本院制剂)、25％葡萄糖注射液     

穿琥宁肠溶胶囊在犬体内的药物动力学及绝对生物利用度

目的　研究穿琥宁肠溶胶囊在犬体内的药物动力学及绝对生物利用度。方法　家犬 6只 ,随机分为 2组 ,采用单剂量交叉给药方案 ,分别给犬单剂量静脉注射或口服穿琥宁肠溶胶囊 ,用HPLC法测定给药后的血中药物浓度 ,3p97药动学程序处理。结果　穿琥宁肠溶胶囊的药 -时数据符合二室模型 ,Cmax为 2 4 .3μg·ml-1,Tmax为 1.2 6h ,AUC(0→∞ ) 为 2 92 84 μg·ml-1,绝对生物利用度为 30 .0 3%。结论　穿琥宁肠溶胶囊有较好的生物利用度     

穿琥宁注射液治疗小儿上呼吸道感染70例疗效观察

观察穿琥宁注射液治疗小儿上感的疗效。穿琥宁治疗组70例(治疗组)与普通治疗组64例(对照组)的疗效作比较。结果治疗组总有效率94.2％,对照组总有效率53.1％,治疗组疗效明显优于对照组(P<0.01)。穿琥宁注射液治疗小儿上感疗效满意,是抗病毒感染中较为理想的中成药制剂。与抗生素合理配伍使用,值得在临床推广使用。     

应用细菌内毒素检查法对注射用穿琥宁进行热源质检测

通过对临床常用的注射用穿琥宁进行细菌内毒素的可行性、干扰试验,结果表明,该制剂用输液溶解后能在1：4以上稀释浓度,用灵敏度为0．25EU／ml以上的鲎试剂对注射用穿琥宁进行细菌内毒素检查,符合药典要求。     

穿琥宁注射液治疗小儿上呼吸道感染70例疗效观察

观察穿琥宁注射液治疗小儿上感的疗效。穿琥宁治疗组70例(治疗组)与普通治疗组64例(对照组)的疗效作比较。结果治疗组总有效率94.2％,对照组总有效率53.1％,治疗组疗效明显优于对照组(P<0.01)。穿琥宁注射液治疗小儿上感疗效满意,是抗病毒感染中较为理想的中成药制剂。与抗生素合理配伍使用,值得在临床推广使用。     

几种中药注射液的过敏性研究

目的:研究参麦注射液、穿琥宁注射液和黄芪注射液在皮肤被动过敏试验(PCA)和全身主动过敏试验(ASA)中是否有过敏反应。方法:按照《中药、天然药物免疫毒性(过敏性、光变态反应)研究的技术指导原则》的试验方法对以上3种中药注射液进行皮肤被动过敏试验和全身主动过敏试验研究。结果:皮肤被动过敏试验麦参注射液和穿琥宁注射液高剂量组和低剂量组均有过敏反应;黄芪注射液高剂量组出现过敏反应,低剂量组未见过敏反应。主动过敏试验只有穿琥宁注射液高剂量组2只动物过敏反应弱阳性,其它未见过敏反应。结论:对于参麦注射液、穿琥宁注射液和黄芪注射液3种中药注射液而言,与临床实际使用情况相比,大鼠皮肤被动过敏性试验具有比全身主动过敏试验更好的相关性。     

静脉滴注赖氨匹林治疗发热患者的疗效观察

目的比较静脉滴注赖氨匹林与复方氨林巴比妥注射液、对乙酰氨基酚片对发热患者的退热疗效。方法选择发热患者120例,随机分成三组,每组40例。A组给予赖氨匹林注射剂0.9g加入0.9%生理盐水100ml静脉滴注;B组给予复方氨林巴比妥注射液（安痛定）2ml肌肉注射;C组给予对乙酰氨基酚片0.5g口服。三组病例用药30min,60min,120min各测体温1次,观察退热疗效。结果赖氨匹林组退热效果最快,用药30min,体温降至（38.5±0.2）℃,总有效率82.5%;用药60min体温降至（37.7±0.3）℃,总有效率90%;用药120min体温降至（36.6±0.4）℃,总有效率95%。在相同条件下,赖氨匹林的退热疗效高于复方氨林巴比妥和对乙酰氨基酚。结论静脉滴注赖氨匹林退热效果快,不良反应小,是理想、安全的退热药物,值得临床推广。     

Alcohol is an effective cue in the conditional control of tolerance to alcohol

To assess the effectiveness of a pharmacological cue as a conditional stimulus in the Pavlovian model of drug tolerance, two groups of Wistar rats received equal numbers of IP injections of a low and a high dose of alcohol. One group (Paired) received a low dose (0.8 g/kg) of alcohol followed 60 min later by the high dose (2.5 g/kg). Another group (Unpaired) received the low and high doses on an unpaired basis. When tested for tolerance to the hypothermic effect of the high dose of alcohol, only the Paired group showed tolerance, and only if the low dose preceded the high. When a saline injection preceded the high dose injection, the Paired group showed a loss of tolerance. The Paired group also showed a compensatory hyperthermia following the low dose injection. Animals from the Paired group that received repeated administrations of the low dose followed by saline, showed a significant extinction effect as compared with animals that received repeated saline injections only. These findings support the Pavlovian model of conditional tolerance, extending the realm of effective conditional stimuli to include a low dose of a drug.     

Eugenol: Antipyretic activity in rabbits

The analgesic agent eugenol reduced fever when given intravenously in small doses to rabbits made febrile by interleukin I. To test this observation further, the drug was given intragastrically and its antipyretic effect was compared with that of a molar equivalent dose of acetaminophen. Eugenol was more effective in reducing fever than acetaminophen. Tests with intracerebroventricular injections indicated that eugenol could act centrally to reduce fever in doses much smaller than those which were effective peripherally. Other tests with the presumed fever mediators sodium archidonate and prostaglandin E₂ (PGE₂), suggest that the central action of eugenol is similar to that of acetaminophen. Eugenol, a derivative of clove oil, has marked antipyretic activity when given intravenously, intragastrically and centrally and may reduce fever primarily through a central action that is similar to that of common antipyretic drugs such as acetaminophen.     

Autogenic-feedback training exercise is superior to promethazine for control of motion sickness symptoms

Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests administered after training.     

Alterations in histamine levels in the rat induced by compound 48/80

Histamine release in the rat was induced in vivo either by a single dose of compound 48/80 injected i.v. or by four repeated, daily doses of the same compound injected i.p. After i.v. injection the levels of blood histamine were determined and after i.p. injections the changes in both tele-methylhistamine and histamine levels in different tissues were investigated. I.v. injection of 48/80 induced a very rapid and marked increase of blood histamine by 7.4 to 11-fold over the control levels within the first two minutes. After repeated i.p. injections of compound 48/80 most tissues showed higher than normal tele-methylhistamine/histamine ratios. The results suggest that agents known to induce release of histamine from mast cells may exert significant changes in blood and tissue histamine levels and that liberated histamine is thereafter extensively catabolized.     

Assessment of beta-blocking activity of low-dose bupranolol

In the present study an investigation was made on the pharmacodynamic effect of the beta-blocking agent bupranolol in the low-dose range. Bupranolol is usually given in doses of 100 mg twice daily in the treatment of hypertension, however the dose range between 20 and 100 mg was studied using graded isoproterenol injections in healthy volunteers. A significant beta-1-blocking activity was observed for the 20 mg dose already. This effect was reduced after a treatment of 10 days. The effect increased with the higher doses, there might be a linear correlation between the logarithm of the dose and the reduction of the tachycardia after the isoproterenol injections in the low-dose range. It was concluded that using the safe and sensitive isoproterenol injection method, the clinical effect of very low doses of bupranolol may be demonstrated. The low dose might be useful to reduce the reflex tachycardia seen in the treatment of hypertension with vasodilating drugs.     

Conditioned saccharin aversions in rats as a result of cutaneous nicotine or intraperitoneal nicotine administered in divided doses

Nicotine base was used in a conditioned taste aversion (CTA) paradigm to avert male Sprague-Dawley rats to saccharin solution (0.1%, w/v). Experiments investigated different dose routes of nicotine administration and duration of action as determinants in nicotine-induced CTA. In Experiment 1 nicotine was injected intraperitoneally (IP) at doses of 0.5, 1.0, or 3.0 mg/kg 30 min after drinking saccharin solution. Using a two-bottle choice test, no CTA was observed, although all nicotine animals showed obvious symptoms of malaise including seizures in the highest dose group. Experiment 2 showed dose-related CTA when nicotine (10.0, 30.0, or 50.0 mg/kg) was cutaneously applied 30 min following saccharin drinking. Experiment 2B showed that the aversions were due to associative rather than nonassociative factors such as sensitization or enhanced neophobia. In Experiment 3, the following group treatments were begun 30 min after saccharin drinking to distribute identical total nicotine doses over an extended period of time: One IP injection of 2.0 mg/kg nicotine (in a saline vehicle) and four injections of saline solution, three injections of 0.67 mg/kg nicotine and two injections of saline, five injections of 0.40 mg/kg nicotine, or five injections of saline. All injections were spaced 30 min apart. Compared with saline-injected controls, CTA occurred in the rats receiving either three or five injections of nicotine but the group receiving one injection did not differ from the control group. There was no difference in CTA between the groups receiving three or five injections.     

Cumulative dose-response curves in behavioral pharmacology

Cumulative dose-response curves have been widely used in many areas of pharmacology. To date, the applicability of cumulative dose-response curves has not been assessed in behavioral pharmacology. To determine the feasibility of this procedure, mice were trained to respond under a multiple time-out 5 min, fixed-ratio 30(mult TO 5, FR 30) schedule of reinforcement. The FR 30 component consisted of 15 presentations of an FR 30hedule of reinforcement. At the start of each TO 5 component, an intraperitoneal (IP) injection was given, and the effect on the response rate during the following 15 presentations of the FR 30 schedule was assessed. d-Amphetamine (0.3–30 μ moles/kg), pentobarbital (3–300 μ moles/kg), morphine (1–100 μ moles/kg), ketamine (3–300 μ moles/kg), and phencyclidine (1–100 μ moles/kg) all produced dose-related decreases in FR responding. In each case the lowest dose tested was without effect, and the highest dose tested essentially eliminated responding. As a control, the normal 4th dose in the ascending series of each drug was given preceded by 3 saline injections. Whether this dose of each drug was preceded by 3 separate saline injections or by 3 lower ascending doses of the same drug, the observed effect was identical. Five consecutive saline injections during the experimental session were without effect. The application of this procedure should greatly decrease the time required to examine the behavioral effects of a wide range of doses.     

The effect of the glycine/NMDA receptor antagonist, (+)-HA966, on morphine dependence in neuropathic rats

We have previously shown that rats with a painful peripheral neuropathy develop dependence without tolerance after repetitive doses [3mg/kg subcutaneously (s.c.)] of morphine. After injections of a higher dose (10mg/kg s.c.) the animals develop tolerance that can be prevented by the glycine/N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-HA966. This study examined whether (1) dependence develops also after repetitive doses of 10mg/kg of morphine and, if so, (2) whether (+)-HA966 prevents the development of dependence after both the low and the higher morphine pretreatment doses. A 4day pretreatment regimen (post-operative days 12-16) with two daily s.c. injections of saline+saline, saline+morphine (3 or 10mg/kg), (+)-HA966 (2.5 or 5mg/kg)+morphine or (+)-HA966 (5mg/kg)+saline was used, and withdrawal was precipitated by an injection of naloxone [2mg/kg intravenously (i.v.)] at 17h after the last pretreatment injection. Three signs of withdrawal (exploring, writhing, ptosis) appeared after pretreatment with both doses of morphine alone, while other signs (teeth chattering, pilo-erection) developed only after injections at the 3mg/kg dose. One sign (penile grooming/erection) appeared only after the higher morphine dose. Pretreatment with the combination of (+)-HA966 and morphine at 3mg/kg prevented the development of all withdrawal signs. By contrast, except for exploring, (+)-HA966 did not modify the incidence of the withdrawal signs observed after pretreatment with doses of 10mg/kg of morphine. The results suggest that prevention of the development of morphine dependence by glycine/NMDA receptor antagonism depends on the degree of morphine dependence.