4,4′-二羟基二苯甲酮的合成

用乙酸酐保护对羟基苯甲酸的羟基,再经氯化亚砜酰氯化、与苯酚成酯得到对乙酰氧基苯甲酸苯酯,最后经脱乙酰保护基和Fries重排得到4,4′-二羟基二苯甲酮,总收率68%.     

应用均匀设计研究4—羟基二苯酮制备工艺

<正> 4—羟基二苯酮是医药化工的基本原料,它是通过苯甲酸苯酯在酸性条件下进行Fries重排而制备得到的。我们应用均匀设计这一统计方法对其工艺条件进行了全面考察,使收率由文献[1]的62%提高到83%,产品质量也有了较大的改善。     

3-甲氧基-4-苄氧基苯甲酸苄酯的合成

3-甲氧基-4-苄氧基苯甲酸苄酯是合成有机药物的一类重要中间体,以香草酸为起始原料,可以有两种合成方法,一种是将香草酸酚羟基苄基化,然后在酸的催化下与苄醇成酯,另一种方法是酚羟基经苄基化,再将羧酸转变为酰氯,最后与苄醇酯化后得产物。反应式如下:     

联苯双酯代谢产物——4-羟基联苯双酯合成的研究

4-羟基联苯双酯(Ⅱ)为联苯双酯(Ⅰ)的代谢产物。本文报道了2-溴-3,4-亚甲二氧基-5-苄氧基苯甲酸甲酯(6)的合成探讨,并将6与2-溴-3,4-亚甲二氧基-5-甲氧基苯甲酸甲酯(8)进行不对称的Ullmann缩合反应,再氢解制得化合物Ⅱ。     

羟基苯甲酸酯类防腐剂MIC法临床抑菌效果评价研究

目的：就羟基苯甲酸酯类防腐剂MIC法临床抑菌效果评价进行了研究和说明。方法通过MIC的方式对羟基苯甲酸酯类防腐剂进行检测,检测其对于尿液中分离菌株、ATCC9027、ATCC8739以及ATCC6538的抑菌效果,并对其抑菌效果进行相应的讨论和分析。同时,对于羟基苯甲酸酯类防腐剂对标准菌株的最小抑菌浓度和羟基苯甲酸酯类防腐剂对尿液中分离菌株的最小抑菌浓度进行分析。结果从羟基苯甲酸酯类防腐剂对标准菌株的最小抑菌浓度中发现,羟基苯甲酸丁酯的抑菌效果最高,其次是羟基苯甲酸丙酯、羟基苯甲酸乙酯,抑菌效果最低的是羟基苯甲酸甲酯。在规定的使用范围内羟基苯甲酸甲酯、羟基苯甲酸乙酯、羟基苯甲酸丙酯和羟基苯甲酸丁酯对于尿液中分离菌株、ATCC9027、ATCC8739以及ATCC6538的抑菌效果显著。同时,标准菌株对于羟基苯甲酸酯类防腐剂的抵抗力较低,而ATCC9027、ATCC8739对于羟基苯甲酸酯类防腐剂的抵抗力较高。结论通过上述实验研究结果的对比分析后发现,羟基苯甲酸酯类防腐剂 MIC 法临床抑菌效果显著,但是其对于尿液中分离的ATCC9027、ATCC8739对于羟基苯甲酸酯类防腐剂的抵抗力较高。     

氨酚氢可酮口服溶液中4种成分的HPLC测定

目的:建立 HPLC 法同时测定氨酚氢可酮口服溶液中主成分(对乙酰氨基酚、重酒石酸氢可酮)和防腐剂(对羟基苯甲酸甲酯、对羟基苯甲酸丙酯)的含量。方法:采用 Zorbax SB-C_(18)柱(4.6 mm×250 mm,5 μm);以0.025 mol·L~(-1)乙酸胺溶液(用冰醋酸调 pH 至4.0)-乙腈(19:81)为流动相 A,0.025 mol·L~(-1)乙酸胺溶液(用冰醋酸调 pH 至4.0)-乙腈(75:25)为流动相 B 进行梯度洗脱;流速为1.0 mL·min~(-1);柱温为35℃;检测波长为280 nm(对乙酰氨基酚)、214 nm(重酒石酸氢可酮)和257 nm(对羟基苯甲酸甲酯和对羟基苯甲酸丙酯)。结果:对乙酰氨基酚、重酒石酸氢可酮、对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的线性范围分别为133.4～1668,2.272～28.40,7.278～90.97,0.7960～9.950μg·mL~(-1);加样回收率(n=9)分别为98.6%,103.7%,100.2%,103.5%。结论:方法简便、准确,可用于氨酚氢可酮口服溶液中4种成分的同时测定。     

3,5-二叔丁基-4-羟基苯甲酸的合成

以2，6-二叔丁基-4-甲基苯酚为原料，在乙酸溶液中与溴反应形成3，5-二叔丁基-4-羟基苯甲醛，然后经Jones氧化得到3，5-二叔丁基-4-羟基苯甲酸，总收率63．7％。     

HPLC法测定硫糖铝凝胶中3种防腐剂的含量

目的建立测定硫糖铝凝胶中苯甲酸钠、对羟基苯甲酸甲酯和对羟基苯甲酸丙酯3种防腐剂含量的HPLC法。方法采用HPLC法,以C18硅烷键和硅胶为固定相;甲醇-10mL·L-1醋酸溶液(60∶40)为流动相;检测波长为254nm;柱温箱温度为35℃;流速为1.0mL·min-1。结果苯甲酸钠、对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的质量浓度分别在20~200,20~200和2~20μg·mL-1范围内呈良好的线性关系;相关系数分别为0.995 3,0.999 1和0.999 1。3组分在3个不同质量浓度水平的回收率分别为:苯甲酸钠98.7%,100.6%和100.4%;对羟基苯甲酸甲酯97.8%,108.0%和104.8%;对羟基苯甲酸丙酯98.3%,100.5%和100.4%(n=9)。苯甲酸钠、对羟基苯甲酸甲酯和对羟基苯甲酸丙酯的峰面积的RSD值分别为0.05%,0.05%和0.04%(n=6)。结论该方法操作简便、快捷,能够准确检测硫糖铝凝胶中3种防腐剂的含量。     

2,5-二苄氧基苯甲酸的制备

以乙醇为溶剂，KI为催化剂，用苄基氯对活泼试剂2，5－二羟基苯甲酸进行羟基保护得到2，5－二苄氧基苯甲酸，收率64％。     

HPLC法快速检测苦参素注射液中8种抑菌剂及苯甲醛

目的:建立快速筛查和同时测定苦参素注射剂中8种抑菌剂(苯甲醇、苯酚、苯甲酸、山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯)及苯甲醇降解产物———苯甲醛含量的高效液相色谱法。方法:应用WelchMaterials XB-C18色谱柱(4.6 mm×250 mm,5μm);流动相为乙腈-0.02 mol.L-1醋酸铵(冰醋酸调pH至5.0)梯度洗脱,流速1.0 mL.min-1,检测波长为211 nm(苯甲醇、苯酚),225 nm(苯甲酸),248 nm(苯甲醛),256 nm(山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯)。结果:9种成分的峰面积与浓度的线性关系良好(r>0.9998),加样回收率为95.6%～102.2%。结论:本方法灵敏,快捷,准确,重复性好,可用于注射剂中抑菌剂的快速筛查与含量分析。     

布洛芬川芎嗪酯的抗炎镇痛作用

目的观察布洛芬川芎嗪酯的抗炎镇痛作用及其胃肠刺激性。方法采用醋酸扭体法、甲醛致痛法、二甲苯致耳肿胀法、角叉菜胶致足肿胀法及醋酸致腹腔毛细血管通透性增加法等实验方法。结果布洛芬川芎嗪酯灌胃给药对冰醋酸、甲醛所致小鼠炎症性疼痛有显著抑制作用 ,能够显著抑制二甲苯所致小鼠耳肿胀和角叉菜胶致足肿胀 ,降低醋酸致小鼠腹腔毛细血管通透性的增加 ,作用与布洛芬相似 ,胃刺激性小于布洛芬。结论布洛芬川芎嗪酯具有抗炎镇痛作用 ,而且不良反应小于布洛芬。     

奥沙普秦凝胶剂的体外渗透性及药效学

目的:研究奥沙普秦凝胶剂体外经皮渗透性及体外释药情况,观察其抗炎镇痛作用。方法:采用Franz扩散池,进行奥沙普秦凝胶剂体外渗透性和释放度实验。采用角叉菜胶致大鼠足肿胀、二甲苯致小鼠耳肿胀、大鼠棉球肉芽肿、醋酸扭体法和甲醛致痛法模型,观察奥沙普秦凝胶剂的抗炎、镇痛作用,同时考察了奥沙普秦凝胶剂皮肤用药的急性毒性、致敏性和刺激性。结果:奥沙普秦凝胶剂对角叉菜胶致大鼠足肿胀、二甲苯致小鼠耳肿胀和大鼠棉球肉芽肿均有明显的抑制作用,对醋酸、甲醛所致小鼠炎症性疼痛有明显抑制作用。急性毒性、致敏性和刺激性实验结果表明奥沙普秦凝胶剂皮肤用药无明显的毒性、致敏性及刺激性。结论:皮肤是奥沙普秦凝胶剂透皮吸收的主要屏障。奥沙普秦凝胶剂具有抗炎镇痛作用,无明显的不良反应。     

不同土炒白术中白术内酯Ⅲ和白术多糖的含量比较

目的:探讨不同辅料土炮制白术对其主要有效成分的影响,为辅料土的筛选提供依据。方法:采用同批药材,用5种不同品种的辅料土炮制;采用高效液相色谱法测定白术内酯Ⅲ的含量,紫外分光光度法测定白术多糖的含量。结果:白术内酯Ⅲ的含量高低为赤石脂炒白术>壁土炒白术>灶心土炒白术>窑土炒白术>黄土炒白术>生白术;多糖含量高低为灶心土炒白术>黄土炒白术>赤石脂炒白术>窑土炒白术>壁土炒白术>生白术。结论:白术经不同辅料土炒炮制后,白术内酯Ⅲ和白术多糖含量均有增高,但不同炮制品之间无显著性差异。     

Synthesis of phosphopeptides containing O-phosphoserine or O-phosphothreonine

Peptides containing phosphoserine or phosphothreonine were synthesized by solid phase methods. Phosphoserine and phosphothreonine were incorporated into peptides using Boc-diphenylphosphono esters of serine and threonine and standard DCC/HOBt coupling. The phenylphosphoesters were not removed when the peptides were cleaved from the resin by HF or by trifluoromethane sulfonic acid, but were subsequently removed by catalytic hydrogenation. Phosphopeptides were purified by HPLC and by Fe⁺³-Chelex chromatography and their identity verified by mass spectrometry. Two peptides, Leu-Arg-Arg-Ala-Ser(P)-Leu-Gly and Leu-Arg-Arg-Ala-Thr(P)-Leu-Gly, were prepared by both enzymatic and chemical methods and had identical properties.     

Influence of several peptidase inhibitors on the pro-inflammatory effects of substance P, capsaicin and collagenase

Injection of substance P (SP) in a rat hindpaw induced extravasation of ¹²⁵I-labelled albumin in both hindpaws and salivation. Intravenous injection of SP dose-dependently increased vascular permeability. This latter effect was increased in rat paws by captopril, an inhibitor of angiotensin-converting enzyme (ACE), administered locally in combination with diprotin A, an inhibitor of an dipeptidyl(amino)peptidase IV (DAP IV) or phosphoramidon, an inhibitor of neutral endopeptidase (NEP). The increase in permeability induced by SP was inhibited by RP 67580, a NK₁-receptor antagonist.Intravenous injection of capsaicin induced labelled albumin extravasation in rat paws. This effect was increased by combination of captopril with diprotin A or phosphoramidon, but not by captopril associated with amastatin, an inhibitor of aminopeptidase M (AmM). It was suppressed by RP 67580.Injection of collagenase in rat paws triggered a swelling and a local plasma exudation. These responses were reduced by RP 67580 but not by RP 68651, its inactive enantiomer. They were increased by combination of captopril with diprotin A or phosphoramidon in normal rats. The potentiating effects of captopril and diprotin A were suppressed by RP 67580 in normal rats but did not develop in kininogen-deficient rats. The oedema induced by collagenase was also increased by lisinopril, another ACE inhibitor, administered locally in combination with apstatin, an inhibitor of aminopeptidase P (AmP). In rats pretreated by methysergide, collagenase-induced oedema was reduced and can be increased by captopril, by lisinopril, administered alone or by lisinopril associated with apstatin.It is concluded that SP is mainly inactivated in rat paws by ACE, DAP IV and NEP In collagenase-induced oedema, a low amount of SP would be released from afferent nerve terminals by bradykinin formed in low amounts. Bradykinin is inactivated in rat paws by ACE and AmP. In collagenase-oedema, the pro-inflammatory effects of bradykinin are concealed by the effects of the other mediators.     

Role of action potentials and calcium influx in ATP- and UDP-induced noradrenaline release from rat cultured sympathetic neurones

Adenine and uracil nucleotides release noradrenaline from rat postganglionic sympathetic neurones by activation of P2X-receptors and distinct receptors for uracil nucleotides, respectively. The present study on cultured neurones of rat thoracolumbal paravertebral ganglia has analysed the involvement of action potentials and calcium influx in the nucleotide-induced transmitter release. ATP and UDP (100 μM each) caused a marked release of previously incorporated [³H]noradrenaline. The P2-receptor antagonists suramin (300 μM) and cibacron blue 3GA (3 μM) decreased the ATP-induced but not the UDP-induced release. The response to ATP was decreased by the sodium channel blocker tetrodotoxin (0.5 μM; by 47%), by the N-type calcium channel blocker ω-conotoxin GVIA (100 nM; by 35%), and by the α₂-adrenoceptor agonist UK-14,304 (1 μM; by 45%); it was not changed by the potassium channel blocker tetraethylammonium (10 mM). The response to UDP was abolished by tetrodotoxin, greatly decreased by ω-conotoxin (by 78%), also abolished by UK-14,304, and increased by tetraethylammonium (by 410%). ATP (100 μM) caused a marked increase in intraaxonal free calcium as measured by fura-2 microfluorimetry. Withdrawal of extracellular calcium diminished the calcium response to ATP by 85%, and tetrodotoxin and ω-conotoxin diminished it by about 40%. As studied with the amphotericin B-perforated patch method, ATP (100 μM) induced a large depolarisation and action potential firing. UDP (100 μM) induced only a small depolarisation but it also elicited action potentials. UDP increased the excitability of the neurones. The results indicate that the ATP-induced release of noradrenaline depends on influx of calcium from the extracellular space. Calcium passes through two structures: voltage-gated channels and – probably – the P2X-receptor itself. Only that component of ATP-induced transmitter release which is triggered by opening of voltage-gated calcium channels is sensitive to modulation by α₂-adrenocep-tors. In contrast to ATP, the UDP-induced release of noradrenaline is entirely due to generation of action potentials followed by calcium influx through voltage-gated channels. All of the UDP-induced release is therefore sensitive to α₂-adrenoceptor modulation. Received: 22 September 1998 / Accepted: 25 January 1999     

Drinking induced by dextran and histamine: relation to kidneys and renin

Intravenous injection of dextran (M.W. 70,000) to rats caused an increased water intake which was accompanied by elevation of plasma renin activity (PRA). The thirst-inducing effect of dextran was abolished by nephrectomy but was unaffected by ureteral ligature. Dextran-induced thirst was blocked by propranolol and by diphenhydramine but the elevation of PRA caused by dextran was not reduced by either of these drugs. Histamine injected subcutaneously to rats increased water intake and elevated PRA. Histamine-induced thirst was only partly reduced after nephrectomy or following administration of propranolol but was completely abolished by diphenhydramine. The elevation of PRA by dextran outlasted the period of increased drinking. The mechanisms involved in the drinking induced by dextran with relation to the kidney, renin and site of action of various blockers are discussed.     

Inhibition by alpha- and beta-adrenoceptors of the twitch response to transmural stimulation in the guinea-pig vas deferens.

Noradrenaline as well as the indirectly acting amines tyramine and phenethylamine either enhance or inhibit the twitch response of the transmurally stimulated, isolated guine-pig vas deferens, thus partly confirming previous reports. In both cases enhancement is annulled by alpha-adrenoceptor blockers. The twitch inhibition caused by noradrenaline is abolished by alpha- + beta2-adrenoceptor blockers, but not by either blocker alone. The inhibition caused by the indirectly acting amines is largely abolished by alpha-adrenoceptor blockers. Clonidine strongly inhibits the twitch. This effect if promptly removed by phentolamine. After blockade of the neurally induced twitch by tetrodotoxin, noradrenaline and the indirectly acting amines have no effect or slightly enhance the twitch elicited by transmural stimulation of the smooth muscle. It is concluded that exogenous noradrenaline acts on postjunctional stimulatory alpha-adrenoceptors and on inhibitory alpha- and beta2-adrenoceptors, which are presumably prejunctional. In the unstimulated preparation contracted by acetylcholine, noradrenaline causes further contraction which is changed into relaxation after phentolamine. This relaxation is abolished by butoxamine, suggesting that noradrenaline may also act on inhibitory postjunctional beta2-adrenoceptors. The twitch-inhibiting effect of endogenous noradrenaline, released by nerve stimulation or by indirectly acting amines, appears to be primarily mediated by prejunctional alpha-adrenoceptors.     

煤工尘肺大阴影的X线片与螺旋CT检查对比分析

目的探讨螺旋CT诊断煤工尘肺大阴影的应用价值。方法回顾对比分析确诊的尘肺大阴影患者的X线胸片与螺旋CT的影像表现并加以比较。结果52例尘肺大阴影中CT检出直径>10mm的融合结节和团块影48例,X线胸片检出39例,CT检出尘肺并发肺气肿42例,X线胸片检出32例,CT检出尘肺并发肺结核7例,肺癌1例,X线胸片检出肺结核2例,CT检出尘肺并发纵隔及肺门淋巴结大或钙化4例,X线胸片检出1例。结论螺旋CT显示尘肺大阴影的影像学特征及并发症的检出优于X线片,对尘肺大阴影的正确,综合诊断具有重要价值。     

山芝麻的抗炎镇痛作用研究

目的研究山芝麻的抗炎镇痛作用。方法山芝麻高剂量31.2 g生药/kg、中剂量15.6 g生药/kg、低剂量7.8 g生药/kg,连续灌胃7 d抗炎实验采用二甲苯致小鼠耳廓肿胀模型和醋酸致小鼠腹腔毛细血管通透性增高模型,镇痛实验采用热板法和扭体法。结果山芝麻能显著抑制二甲苯引起的小鼠耳廓肿胀,抑制醋酸引起的小鼠腹腔毛细血管通透性增高,并降低小鼠热板痛阈值,减少醋酸引起的扭体次数。结论山芝麻具有抗炎镇痛作用。