水杨酸及其衍生物透皮吸收的研究

目的研究水杨酸及其衍生物的透皮吸收.方法用丙二醇作促透剂,用改良的Franz扩散池进行离体大鼠皮体外释放试验,紫外法测定累积释放量,计算平均透皮速率.结果含丙二醇乳膏中各药物的透皮速率分别为水杨酸38.722 5μg·cm2·h-1,赖氨匹林16.882 1μg·cm2·h-1,阿司匹林10.121 5 μg·cm2·h;不含丙二醇乳膏各药物透皮速率分别为水杨酸29.765 7μg·cm2·h-1,赖氨匹林10.690 0μg·cm2·h-1,阿司匹林6.965 3 μg·cm2·h-1.结论两种乳膏水杨酸、赖氨匹林、阿司匹林透皮速率差异显著;丙二醇对赖氨匹林和阿司匹林均有显著的促透作用.     

注射用赖氨匹林治疗急重症高热临床疗效观察

目的：比较注射用赖氨匹林与安痛定注射液的退热疗效。方法：选择高热患者94例，随机分为3组，分别静滴注射用赖氨匹林，肌注赖氨匹林注射液，肌注安痛定注射液退热，进行疗效比较。结果：用药60min后赖氨匹林静滴组平均降温2．01℃，显效率为56．25％，肌注组平均降温1．72℃，显效率为46．67％，安痛定组平均降温0．98℃，显效率为9．37％。结论：赖氨匹林注射液退热快，疗效好，副作用少。     

赖氨匹林不良反应中文文献分析

目的:为临床合理应用赖氨匹林提供参考。方法:对国内近年应用赖氨匹林出现的不良反应报道进行整理、归纳和分析。结果:归纳总结出了赖氨匹林不良反应发生的一般规律和特征。结论:临床在应用赖氨匹林时,应高度关注其不良反应的严重危害。     

赖氨匹林与卡氮芥协同抗肿瘤作用的研究应用

目的 探讨赖氨匹林与卡氮芥协同抗肿瘤的作用价值.方法 通过基础实验、动物实验与临床观察等三大部分对赖氨匹林与卡氮芥作用进行研究.结果 ①基础实验：赖氨匹林对C6细胞具有促凋亡和增殖抑制作用;②动物实验：赖氨匹林与卡氮芥联合使用对胶质瘤具有显著性治疗作用;③临床观察：脑胶质瘤术后36例患者随访18个月,赖氨匹林、卡氮芥联合组疗效明显优于无化疗组和卡氮芥组.结论 赖氨匹林＋卡氮芥对动物模型胶质瘤有显著治疗效果.收集脑胶质瘤术后患者,初步证实赖氨匹林的抗胶质瘤的作用和它在神经外科临床中的应用前景.     

赖氨匹林在急诊儿科发热性疾病中的应用观察

目的：观察赖氨匹林对小儿高热的退热效果。方法：选择200例高热患儿,将其随机分为赖氨匹林组和安痛定组,分别用赖氨匹林和安痛定肌注退热,观察体温变化,进行疗效比较。结果：两组患儿用药30min及1h后观察体温变化,赖氨匹林组显效率分别为84.7%和98.0%,安痛定组显效率分别为40.0%和86.0%,赖氨匹林组退热效果优于安痛定组,且观察期间无不良反应发生。结论：赖氨匹林起效快,效果好,疗效肯定,无不良反应,是治疗小儿高热的有效药物。     

布洛芬混悬液与赖氨匹林注射液临床疗效比较

目的:比较布洛芬混悬液与赖氨匹林注射液对急性呼吸道感染高热患儿的退热效果。方法:急性呼吸道感染高热患儿(腋温>39℃)105例随机分成两组,分剐用布洛芬混悬液和赖氨匹林注射液治疗。结果:在0.5 h内赖氨匹林退热速度较快。在0.5-1 h布洛芬混悬液和赖氨匹林注射液的退热效果相同,布洛芬混悬液在2 h内能使患儿体温降至正常,并维持8 h。布洛芬混悬液对咽痛、头痛的缓解比赖氨匹林更为显著。结论:布洛芬混悬液退热疗效类似于赖氨匹林,口服方便。     

注射用赖氨匹林细菌内毒素检查法的研究

目的:研究注射用赖氨匹林的细菌内毒素检查方法。方法:用不同厂家生产的鲎试剂对注射用赖氨匹林进行细菌内毒素检查法干扰试验。结果:注射用赖氨匹林在稀释至3.12 mg/ml时,对灵敏度为0.25 Eu/ml的鲎试剂无干扰作用。结论:注射用赖氨匹林可以用细菌内毒素检查法取代热原检查法。     

赖氨匹林与对乙酰氨基酚栓治疗小儿发热疗效比较

目的：比较对乙酰氨基酚栓与注射用赖氨匹林对急性呼吸道感染伴高热患儿的退热效果。方法：选择有急性呼吸道感染伴有发热症状的患儿100例,随机分为2组,分别给予对乙酰氨基酚栓、赖氨匹林注射液治疗。结果：在1h内赖氨匹林的退热速度较快,与对乙酰氨基酚栓有统计学差异（P〈0．01）;在1～2h,对乙酰氨基酚栓的退热速度显著地快于赖氨匹林（P〈0．01）。赖氨匹林在2h内能使患儿体温降至正常,并维持较长时间,6h后体温呈回升趋势。对乙酰氨基酚栓组服药后3h体温呈回升趋势,且体温回升较赖氨匹林组快。赖氨匹林注射液的总有效率为100％,对乙酰氨基酚栓的总有效率为94．0％。赖氨匹林组退热的显效率为92．0％,对乙酰氨基酚栓组为36．0％;两组的差异有统计学意义（P〈0．01）。结论：赖氨匹林的退热作用强,维持时间长。     

注射用炎琥宁与赖氨匹林配伍的稳定性研究

目的考察在不同温度（25℃、37℃）条件下，炎琥宁与赖氨匹林配伍后8h内的稳定性。方法模拟临床用药浓度，将炎琥宁与赖氨匹林配伍后，采用紫外分光光度法，考察不同温度、不同时间下配伍液中2种药物的含量变化，测定pH值，同时观察外观。结果炎琥宁与赖氨匹林配伍是稳定的。     

赖氨匹林退热作用观察

赖氨匹林是赖氨酸和阿司匹林的复盐,水中溶解度好,能作肌肉和静脉注射。本文选择26例因感冒等疾病引起发热,以4ml赖氨匹林肌肉注射,用药后30分钟开始退热,180分钟体温基本正常。另选15例对照病例用1ml安乃近肌肉注射,退热情况基本与赖氨匹林相似。因此认为赖氨匹林可作为较好的退热药物。     

Effects of lysine aspirin on lung AQP5 expression and lymphocyte apoptosis in paraquat-poisoned rats

Objective: This study explored the effects of lysine aspirin on lung aquaporin 5 (AQP5) expression and lymphocyte apoptosis in paraquat-poisoned rats. Methods: Thirty healthy male Wales rats were randomly divided into three groups (n?=?10): the control group received 0.9% sodium chloride (0.4?mL, intragastric administration; 0.8?mL, intraperitoneal injection); the paraquat group received 40?mg/kg paraquat (intragastric administration) and 0.9% sodium chloride (intraperitoneal injection); and the paraquat + lysine aspirin group received 40?mg/kg paraquat (intragastric administration) and 20?mg/kg lysine aspirin (intraperitoneal injection). Rats were killed at 24 and 48?h. RT-PCR and immunohistochemical staining were performed in lung tissue to determine the AQP5 mRNA and protein expression. Blood from the arterial vein was used to evaluate lymphocyte apoptosis. Results: The lung tissue of paraquat-treated rats displayed pulmonary hemorrhage, interstitial edema and inflammatory cell infiltration. AQP5 mRNA and protein expression in the paraquat-treated group decreased after 24 and 48?h, whereas the peripheral blood lymphocyte apoptosis ratio significantly increased. In contrast, paraquat + lysine aspirin treatment ameliorated these changes. Conclusion: Paraquat decreases AQP5 expression in rat lungs and increases peripheral blood lymphocyte apoptosis. Lysine aspirin can reduce these alterations.     

Dissolvable polymeric microneedles loaded with aspirin for antiplatelet aggregation

To reduce mucosal damage in the gastrointestinal tract caused by aspirin, we developed a dissolvable polymeric microneedle (MN) patch loaded with aspirin. Biodegradable polymers provide mechanical strength to the MNs. The MN tips punctured the cuticle of the skin and dissolved when in contact with the subcutaneous tissue. The aspirin in the MN patch is delivered continuously through an array of micropores created by the punctures, providing a stable plasma concentration of aspirin. The factors affecting the stability of aspirin during MNs fabrication were comprehensively analyzed, and the hydrolysis rate of aspirin in the MNs was less than 2%. Compared to oral administration, MN administration not only had a smoother plasma concentration curve but also resulted in a lower effective dose of antiplatelet aggregation. Aspirin-loaded MNs were mildly irritating to the skin, causing only slight erythema on the skin and recovery within 24 h. In summary, aspirin-loaded MNs provide a new method to reduce gastrointestinal adverse effects in patients requiring aspirin regularly.     

Studies of the chemical selectivity of hapten, reactivity, and skin sensitization potency. 2. nmr studies of the covalent binding of the (13)c-labeled skin sensitizers 2-[13C]- and 3-[13C]hex-1-ene- and 3-[13C]hexane-1,3-sultones to human serum albumin

3-[(13)C]- and 2-[(13)C]hex-1-ene-1,3-sultones (1a and 1b, respectively) and 3-[(13)C]hex-1-ene-1,3-sultone 2a were incubated with human serum albumin in phosphate buffer at pH 8.1. In both cases, the main reaction was a hydrolysis via an S(N) reaction at position 3, but several adducts were also formed. Hex-1-ene-1,3-sultone, which is a strong skin sensitizer, appears also to be a strongly oxophilic molecule reacting mainly at position 3 through an S(N) reaction to give adducts on tyrosines. This sultone was also able to react with a single lysine residue, also via an initial S(N) reaction at position 3, followed by an intramolecular Michael addition at position 2 to form a mixture of aziridinium intermediates which were subsequently hydrolyzed to give an amino alcohol derivative as the final product. The same reaction carried out on acetylated human serum albumin seems to indicate that the target lysine could be Lys199, which is known to be easily acetylated. Hexane-1,3-sultone, which is a weak sensitizer, appears to be an even more oxophilic molecule, making adducts on tyrosines through an S(N) reaction at position 3. No reaction was observed on Lys199. The difference in skin sensitization potential seems therefore to be more related to the selective ability of modifying lysine residues than to the more general ability to modify tyrosine residues.     

赖氨匹林加甲氧氯普胺治疗偏头痛

目的 :评价赖氨匹林加甲氧氯普胺治疗偏头痛的疗效与安全性。方法 :偏头痛病人 10 4例分成 2组 :治疗组 52例 ,男性 15例 ,女性 37例 ,年龄35a±s 12a ;对照组 52例 ,男性 13例 ,女性 39例 ,年龄 37a± 11a。头痛发作时 ,病人随机交替口服内含赖氨匹林 0 .9g加甲氧氯普胺 10mg的胶囊(治疗组 )或内含淀粉的胶囊 (对照组 ) 1粒。结果 :治疗组服药 4h总有效率为 88% ;对照组总有效率为 2 9%。 2组总有效率比较差别有非常显著意义(P <0 .0 1) ,未见严重不良反应。结论 :赖氨匹林加甲氧氯普胺治疗偏头痛安全、可靠。     

Alterations in platelet alpha 2-adrenoceptors by aspirin

Epinephrine-induced platelet aggregation (mediated through interaction with alpha 2-adrenoceptors) is inhibited by aspirin. To determine if aspirin modulates alpha 2-adrenoceptors, we quantitated dissociation constant (KD) and maximum number of binding sites (Bmax) on isolated platelet membranes using alpha 2-antagonist 3H-yohimbine in normal subjects given 650 mg of aspirin orally. Alpha 2-receptor KD increased from 3.20 +/- 1.80 to 7.32 +/- 3.32 nM (p less than 0.02) and Bmax from 115 +/- 77 to 190 +/- 140 fmol/mg protein. To determine if these alterations in alpha 2-receptors by aspirin were mediated through circulatory or intracellular effects, intact platelets or isolated platelet membranes were incubated with aspirin for 30 minutes in vitro. In these in vitro experiments, alpha 2-receptor KD increased from 2.92 +/- 1.76 to 9.83 +/- 8.55 nM and Bmax from 140 +/- 81 to 191 +/- 129 fmol/mg protein (p less than 0.05). Oral ingestion of aspirin or incubation of aspirin with intact platelets or lysates increased (3 to 10 fold) the concentration of 1-epinephrine required for inhibition of 3H-yohimbine binding by 50% (p less than 0.05). Basal platelet cyclic AMP as well as its elevation with PGE1 or PGI2 and decrease with catecholamines were not influenced by aspirin treatment of platelets. These data indicate that aspirin decreases platelet alpha 2-receptor affinity for agonist as well as antagonist. These effects of aspirin are independent of circulatory or dynamic intraplatelet changes.     

Effects of administration route on pharmacokinetics of aspirin in the rabbit

The absorption of aspirin used in the form of lysine acetylsalicylate was studied in the rabbit. Each animal received the drug by three routes: intravenous, gastric and duodenal. Plasma concentrations of acetylsalicylic acid (ASA) and salicylic acid (SA) were compared. ASA plasma concentrations obtained after gastric or duodenal administration were low compared to those after intravenous injection. Concentrations were 2 to 5 times higher after gastric than duodenal administration. SA plasma concentrations were lower at the beginning of the experiment for gastric than for duodenal administration; after 90 min the concentrations were similar. A better absorption of aspirin (as lysine acetylsalicylate) after administration occurred in the stomach than in the duodenum, but the amount of ASA which reached the central compartment was quite poor.     

Reaction of human albumin with aspirin in vitro: Mass spectrometric identification of acetylated lysines 199, 402, 519, and 545

The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid-free human albumin and human plasma were treated with aspirin for 5 min-24 h. Acetylated residues were identified by LC/MS/MS and MALDI-TOF/TOF mass spectrometry of tryptic peptides. Treatment with 0.3 mM aspirin resulted in acetylation of Lys-199, Lys-402, Lys-519, and Lys-545. Treatment with 20 mM aspirin resulted in acetylation of 26 lysines. There was no acetylation of Tyr-411, under any conditions. Acetylated lysine was stable for at least 21 days at pH 7.4, 37 °C. Albumin acetylated by aspirin had reduced esterase activity with β-naphthyl acetate as shown on gels stained for esterase activity. It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate.     

Aspirin reduces adverse effects of gefitinib

We measured serum levels of soluble (s) P-selectin and thromboxane B2 (TxB2) in patients with lung cancer treated with gefitinib, and investigated the effect of low-dose aspirin on some adverse effects of gefitinib. The serum levels of sP-selectin and TxB2 increased significantly in all patients who received gefitinib for 2 weeks. Forty patients were recruited, and 28 received gefitinib without low-dose aspirin (Group 1) and 12 were co-administered low-dose aspirin (Group 2). In Group 2, the frequency of adverse events, skin rash and diarrhea was evidently reduced by the low-dose aspirin therapy, despite having shown no remarkable change in gefitinib responsiveness between both groups. In one of the 12 patients in Group 2, aspirin therapy was suspended due to the occurrence of nasal bleeding. Four days after treatment suspension, she developed a skin lesion in her finger. However, the skin lesion improved after re-administration of aspirin without any other medications. After treatment, TxB2 significantly decreased, but not sP-selectin. These results suggest that one of the mechanisms causing gefitinib-related adverse effects depends on platelet activation. Administration of gefitinib with low-dose aspirin to lung cancer patients may prevent the development of gefitinib-related complications.     

Effect of vitamin E and other amelioratory agents on the fenvalerate-mediated skin sensation

Previous investigations have demonstrated that dermal exposure to fenvalerate or other synthetic pyrethroid insecticides can produce a skin sensory response characterized by an itching/tingling sensation in humans and animals. The objective of this investigation performed in guinea pigs was to establish treatments which would be effective against pyrethroid-mediated skin sensation. Two classes of agents were tested. Barrier agents, which block penetration of substances through the skin, did not significantly reduce the fenvalerate-mediated skin sensations. Post-treatments with steroidal Dermolate, antihistamine Delamine or anti-inflammatory aspirin did not significantly reduce the pyrethroid-mediated skin sensation. However, Bicozene (a local anesthetic cream) and Tashan (a vitamin A, D, and E-containing cream) were effective in reducing the pyrethroid-mediated skin sensations. Prior (30 min and 5h) dermal application of vitamin E was found to be effective in significantly reducing the fenvalerate-mediated skin sensation; even when applied 29 h prior to fenvalerate exposure, there appeared to be a reduced skin response. Piperonyl butoxide (PBO), a pesticide synergist, reduced the fenvalerate skin sensations when applied either directly to the skin or in conjunction with the pyrethroid.     

Effect of aspirin on serotonin and met-enkephalin in brain: correlation with the antinociceptive activity of the drug

Intravenous administration of acetyl salicylate of lysine, a soluble salt of aspirin, reduced in rats the firing discharge of thalamic neurones, evoked by noxious stimuli. Concomitantly, concentrations of 5-hydroxyindole acetic acid increased, while those of met-enkephalin-like immuno-reactive derivatives were decreased in several areas of the brain. Similar electrophysiological and biochemical responses were obtained by administering tryptophan or 5-hydroxytryptophan plus carbidopa. The effect of aspirin on the evoked firing of the thalamic neurones was counteracted by pretreating the animals with metergoline. On the other hand, naloxone did not antagonize the inhibitory effect of aspirin and 5-hydroxytryptophan on pain-induced neuronal excitation. These data indicate that a serotonin-, but not a naloxone-sensitive opiate mechanism, may be relevant for aspirin-mediated antinociception.