Stability of Lidocaine in Aqueous Solution: Effect of Temperature,pH, Buffer,and Metal Ions on Amide Hydrolysis

The degradation of lidocaine in aqueous solution obeys the expression k _obs = (k _H+[H ⁺] + k _o ) [H⁺]/([H ⁺ ] + K _a + k_o K _a([H ⁺ ] + K _a) where k _H+ is the rate constant for hydronium ion catalysis, and k _o and k_o are the rate constants for the spontaneous (or water-catalyzed) reactions of protonated and free-base lidocaine. At 80°C, the rate constants for these processes are 1.31 × 10^–7 M ^–l sec^–1, 1.37 × 10^–9 sec^–1, and 7.02 × 10^–9sec^–1; the corresponding activation energies are 30.5, 33.8, and 26.3 kcal mol^–1, respectively. It was found that the room temperature pH of maximum stability is 3–6 and that lidocaine is more reactive in the presence of metal ions such as Fe²⁺ and Cu²⁺. The dissociation constant, K _a, for lidocaine at 25–80°C was also measured at 0.1 M ionic strength and a plot of pK _a versus 1/T gave a slope of (1.88 ± 0.05) × 10³ K^–1 and intercept 1.56 ± 0.16.     

改质炉高温炉管运行损伤及剩余寿命分析

对高温运行70000h至90000h改质炉炉管进行试验研究及材料损伤分析,结果表明,炉管的材料性能已严重劣化（脆化）,炉管的内外壁已有微小裂纹萌生,测定了炉管材料在950℃、各种应力水平下的断裂时间,根据时间-温度参数L-M公式,推测炉管的剩余寿命为8510h。     

前列腺素E1治疗老年慢性肺心病急性期的疗效观察

目的 :探讨前列腺素E1(PGE1)对老年慢性肺心病急性期的疗效。方法 :对 40例老年慢性肺心病急性期患者应用PGE110 0 μg·d-1静脉滴注 ,疗程 7d。于治疗前后同步检测患者血浆D -二聚体 (D -dimer) ,血清纤维蛋白降解产物 (FDP) ,动脉血氧分压 (PaO2 ) ,及动脉血二氧化碳分压 (PaCO2 )并观察症状体征变化 ,同时与对照组患者及 2 0例健康者进行比较。结果 :两组老年慢性肺心病急性期患者的D -二聚体和FDP显著高于健康组 (P <0 .0 1) ,治疗组病例治疗后D -二聚体及FDP较治疗前显著降低 (P <0 .0 1) ,症状体征显著改善 (P <0 .0 5～ 0 .0 1) ,对照组的D -二聚体 ,FDP及部分症状和体征 ,治疗前后比较差异有显著性 (P <0 .0 5～ 0 .0 1)。治疗后PaO2 两组均显著增高 (P <0 .0 1) ,组间比较无差别 (P >0 .0 5 )。治疗后PaCO2 两组均降低 ,但治疗组降低幅度更明显 (P <0 .0 1)。结论 :PGE1对老年慢性肺心病急性期确有良好疗效     

Differential Effects of Anionic,Cationic, Nonionic,and Physiologic Surfactants on the Dissociation, α-Chymotryptic Degradation,and Enteral Absorption of Insulin Hexamers

Various surfactants were investigated to compare their effects on insulin dissociation, -chymotryptic degradation, and rat enteral absorption. With a circular dichroism technique, sodium dodecyl sulfate (SDS) at a 5 mM concentration was found to completely dissociate procine-zinc insulin hexamers (0.5 mg/ml) into monomers. The catalytic activity of -chymotrypsin (0.5 µM) was also abolished by 5 mM SDS. When insulin was injected into the distal jejunum/ proximal ileum segment of the rat, 5 mM SDS greatly enhanced its pharmacological availability, from a negligible value to 2.8%. Being a cationic surfactant, hexadecyl trimethylammonium bromide (CTAB) also efficiently dissociated insulin hexamers at concentrations of 1–5 mM. However, extensive charge–charge interaction was observed below a CTAB concentration of 0.6 mM, leading to insulin precipitation at a molar CTAB:insulin ratio of 1:1 to 2:1. An -chymotryptic degradation study also revealed near-complete dissociation of insulin hexamers at 1 mM CTAB. Above 1 mM, however, CTAB acted as an enzyme inhibitor, most likely by means of charge repulsion. Enteral absorption studies showed a much lower pharmacological availability, only 0.29%. Nonionic surfactants such as Tween 80 and polyoxyethylene 9 lauryl ether were ineffective in dissociating insulin hexamers. Tween 80, at 5 mM, neither significantly altered the -chymotryptic degradation pattern nor enhanced the enteral absorption of insulin. The relative effectiveness of different species of bile salts on insulin hexamer dissociation appeared to be similar. Sodium glycocholate at a 30 mM concentration also significantly increased insulin pharmacological availability, to 2.3%. A morphological study did not reveal any significant alteration of the rat intestinal mucosal integrity after exposure to 5 mM SDS for 30 min. The results further emphasize the importance of the degree of insulin aggregation on its enteral transport.     

甲基酚烯酸酯树脂的热裂解机理

研究了以甲基丙烯酸酯端基不饱和取酯树脂为主链,用甲基丙烯酸甲酯取代苯乙烯作为交联剂制成的甲基丙烯酸酯树脂（ＭＡＥＲ）与通用型不饱和聚酯树脂（ＧＵＰＲ）的热裂解机理、燃烧现象。结果表明：ＭＡＥＲ的裂角产物中苯环化合物含量（１４．９％）少于ＧＵＰＲ（７４．５％）。ＭＡＥＲ燃烧时的发烟量和毒性也远低于ＧＵＰＲ。在ＭＡＥＲ中加入三水合氧化铝（ＡＴＨ）后,裂解产物中有毒物质的各类和数量更少,在燃烧时只有少量     

血中纤维蛋白降解产物和D—二聚体水平对硅沉着病早期诊断意义 …

目的：探讨纤维蛋白降解产物（ＦＤＰ）和Ｄ－二聚体（Ｄ－Ｄｉｍｅｒ）两项指标在硅沉着病（原称矽肺）早期诊断中的意义和价值。方法：用ＥＬＩＳＡ法测定正常人、接尘工人和不同期别的硅沉着病病人血中ＦＤＰ和Ｄ－Ｄｉｍｅｒ含量变化并测定其他指标。结果：硅沉着病早期ＦＤＰ和Ｄ－Ｄｉｍｅｒ水平很高,随着硅沉着病的晋期,ＦＤＰ和Ｄ－Ｄｉｍｅｒ水平逐渐下降。结论：ＦＤＰ和Ｄ－Ｄｉｍｅｒ作为硅沉着病早期诊断指标具有一下     

止咳平喘膜剂的经效学研究（1）

本文对止咳平喘膜剂的药效学进行了初步的研究,结果表明,该膜剂经皮给药能显著延长蛋清所致朋鼠哮和枸橼酸所致豚鼠咳嗽的潜伏期,减少枸橼酸所致豚鼠的咳嗽次数,对小鼠气管酚红排泌量有明显的促进作用,加快小鼠碳粒廓清速率,无论是抗原攻击关给药,还是攻击后给药均可显著抑制２,４－二硝基氯苯所性皮炎。     

Analytical Chiral Separation of the Stereoisomers of a Novel Carbonic Anhydrase Inhibitor and Its Deethylated Metabolite,and the Assignment of Absolute Configuration of the Human Metabolite and Chiral Degradation Products

Several approaches to the separation of four stereoisomers, 1–4, of a novel, topically active, carbonic anhydrase inhibitor, 1, with two chiral centers in the molecule and four isomers, 5–8, of its chiral metabolite, 5, were evaluated. These methods include nonchiral derivatization followed by separation on chiral stationary phases (CSPs) and chiral derivatization and separation on nonchiral columns and on CSPs. Baseline separation of stereoisomers 1–4 was achieved in less than 15 min after chiral derivatization with (S)-(+)-l-(l-naphthyl)ethyl isocyanate (NEIC) and chiral chromatography on a (R)-N-(3,5-dinitrobenzoyl)phenyl glycine (DNBPG) column under normal phase (NP) conditions. Similarly, isomers 5-8 were baseline separated in less than 20 min after derivatization with NEIC and chromatography on nonchiral (nitrophenyl) and chiral [(S)-(3,5-dinitrobenzoyl)leucine; DNBL] columns in series under the same NP chromatographic conditions. Only partial separation of the diastereomeric derivatives was observed on a variety of nonchiral columns. In addition, all other direct and indirect chiral separation approaches gave only partial separation of at least two stereoisomers within the group of 1–4 or 5–8. The details of chiral separations using various methods and separation () and capacity factors (k) of the derivatized isomers 1–8 on a series of chiral and nonchiral columns are presented. Using these methods, the absolute configuration of the human metabolite of 1 was established as S ₁ S ₂ (5), and the heat (HD) and light (LD) degradation products of 1 as R ₁ S ₂ (3) and S₁ S ₂ (5), respectively.     

十二烷基硫酸钠在天然水体中的降解作用

本文研究了十二烷基硫酸钠在天然水体中的降解作用,结果表明十二烷基硫酸钠在天然水体中的降解主要依赖于微生物的降解。微生物最适降解条件为ｐＨ６．５～９．４和３６℃左右。降解作用随温度升高（４～３６．５℃）和微生物浓度增大而加快,用十二烷基硫酸钠预先驯化微...     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.