10%苯巴比妥钠注射液贮存期预测

The shelf-life of 10% sodium phenobarbital injection(containing propylene glycol 60%) has been predicted by accelerated stability test with the classical isothermal method (at 100, 90, 80 and 70℃). The data was treated with regressive calculation, and the shelf-life calculated with three different methods (regressive calculation, average activation energy calculation and graphical plotting).The values obtained from these three methods were approximately equal, and also coincided with the value obtained from samples reserved for observation at room temperature. The shelf-life was 1.05 years at 25℃, and 2.03 years at 20℃.     

苯巴比妥钠注射液的分解产物

A major degradated product was obtained from sodium phenobarbital injection stored at room temperature or heated at 100℃ for a long time. It was identified by means of melting point, optical rotation, UV and IR spectrum, elemental analysis and paper chromatography to be dl-pheneturide irrespective of the source of sample.A search in the literature showed that this degradated product is a potent anticonvulsant.     

硝苯啶的光解分析法及其在透皮吸收研究中的应用

A new method of analysis for low concentrations nifedipine was developed according to the principle of a photodegradation analytical method that has been reported by the authors previously, and was used to study percutaneous absorption. The absorbance of sample solution was measured before and after light irradiation at 237 nm for 2 h. In this method, calibration graph was linear in the range of 1～20μg/ml for △A₂₃₇. The average recovery for nifedipine was 98.80%. No interference from propylene glycol, azone, m-nifedipine, nitrendipine, verapamil and propranolol was observed. It is shown that azone can promote markedly percutaneous absorption of nifedipine.     

脑内注射白细胞介素-1β对淋巴结细胞应激免疫抑制因子生成的影响

our previous work showed that a suppressive factor( a protein with largemolecular weight in serum was induced by restraint stress in mice and rats,which suppressed Con Ainduced lymphocyte proliferation.It was also found that the generation of serum suppressive factorwas under control of the central nervous system.Our further study showed thatintracerebroventricular(icv )injection of interleukin 1 receptor antagonist(IL-1Ra)antagonised thegeneration of serum suppressive factor induced by restraint stress and icv injection of interleukin-1β(IL-1β)increased the generation of the suppressive factor.Our experiment also showed that the serumsuppressive factor induced by restraint stress was first made in lymph tissue and then released intoblood.The present work was designed to investigate the role of IL-1 in the brain in generation of thesuppressive factor in lymph node in mice.Icv injection of IL-1β( 1 pg/mouse) was shown tosignificantly increase the generation of the suppressive factor in lymph node.Icv injection of IL-1Ra,however ,antagonised generation of the suppressive factor.In mice without restraint stress,both thesuppressive factor in serum and in lymph node were found to be induced in dose-dependent manner byicv injection of IL-1β.Taken together,these results suggest that IL-1β in brain played a veryimportant role in generation of the suppressive factor in lymph node.The positive correlation betweenthe suppressive action of lymph node and of serum added to the evidence that lymph tissue is probablythe source of the serum suppressive factor.     

β-LACTAMASE INHIBITORS

It is now well established that among the penicillins and cephalosporins,one of the most important mechanisms of resistance is the production of theenzyme,β-lactamase.This enzyme is widely distributed among Gram-positiveand Gram-negative bacteria and in recent years the frequency of β-lactamaseproducing strains in many important pathogens bas increased significantly.Table 1 shows the frequency of penicillin-resistant Staphylococcusanreus in the Outpatients Department of one London hospital. It willbe seen that more than 80％ of these isolates are now penicillin-resistantwhich means they are also resistant to ampicillin,amoxycillin and to otherpenicillins.No longer can we say that β-lactamase-producing Staph.aureusare confined to the hospital.     

云南白珠属植物精油及其利用研究

Within the Genus gaultheria L., G. forrestii Diels, G.yunnanensis (Franch.) Rehd.and G. griffithiana Wight are the most widely distributed species in Yunnan. The essential oils derived from them mainly consist of methyl salicylate, and the contents amount to 94—99%. When we undertook the synthesis of 3,3-methylene bis-(4-h)hydroxycoumarin) from methyl salicylate by M.A.Stahman's procedure, we found that during the step of forma- tion of 4-hydroxycoumarin by treating methyl acetyl salicylate with metallic sodium, it would be better to use a ratio of the ester and sodium at ten to one by weight; the reacting temperature was controlled within a range at 180—200℃, and the reaction was prolonged about two hours. By so doing, the yield of 4-hydroxycoumarin was raised from Stahman's 22% to a new leval of 30—31%.     

Purification and Characterization of Hepatocyte Regeneration Stimulatory Factor from Shark Liver

Aim To purify hepatocyte regeneration stimulatory factor from shark liver and research its molecular feature and activity. Methods and Results Hepatocyte regeneration stimulatory factor (sHRSF) was isolated from healthy shark livers and separated by homogenization, freezing-melting, heat treating, centfifugation, and ultmfdwation. HRSF activity was found mainly in the subfraction of molecular weight less than 30 000 daltons. This crude ultrafihrate was further purified successively by DEAE-Sepharose fast flow chromatography, FPLC Resource 30Q, Resource Q and Mono Q chromatography.A single band was displayed on sodium dodecyl sulfate polyacrylamide gel electrophoresis, which corresponds to molecular weight of 14 600 daltons. The characteristic absorption was obtained at the wavelength 276 nm. The isoelectric point was about 5.1. It contained 18 amino acids and the 15 N-terminal amino acid residues were LVGPIGAVGPAGKDG. It had a significant activity in stimulating liver to regenerate. Condusion We obtained an unknown new active protein, that is hepatocyte regeneration stimulatory factor from shark liver ( sHRSF).     

植物多糖在胃肠道及肝病中的新作用

The polysaccharide fraction from various herbal medicines has been well studied for its immunomodulatory action and antitumor effect, such as lentinan and lucid Ganoderma, for more than twenty years. These actions and effects may be due to stimulation of the phagocytic activity and anti-inflammatory action. It is also found to increase hematopoiesis in the bone marrow and to promote proliferation of several types of hematopoietic precursor cells. It was also found to provide radioprotective effect by improving the recovery of hematopoietic function in animals. These findings suggest that the polysaccharides from plant origins have significant pharmacological action on cells with high proliferative capacity in the body. Recently, increasing evidence implicates that vegetal polysaccharides have similar protective and repairing activities in the gastrointestinal (GI) tract as the cells in this system also have the same biological property. In this review, we would like to update and summarize findings both in animals and in human pertaining to the pharmacological actions of polysaccharides from different vegetal sources on the GI and hepatic disorders including ulcer and cancer diseases.     

The generation of IPSP was antagonized by injection of 6-OHDA

In the present study 6 hydroxydopamine (6-OHDA) was used for chemical sympathectomy and the effect of 6-OHDA on generation of immune suppressive protein of stress (ISPS) was studied.It was found that the generation of ISPS was significantly suppressed.The maximal suppression was found on d 5 after 6-OHDA injection and it recovered gradually to normal on d 14.In order to assess the effectiveness of the 6-OHDA injection, the contents of norepinephrine (NE) in spleen and lymph node were assayed by high performance liquid chromatography-electrochemical detector (HPLC-ED).NE was     

大子蒿对下丘脑—垂体—肾上腺皮质系统的影响

Pharmacological effects of Tibetan medical plant Artemisia sieversiana on the hypothalamo-pituitary-adrenocortical axis are reported in present paper.The alcoholic (60%) extract of A. sieversiana (AEAS) injected intraperitoneally at 460 mg/kg in rats enhanced significantly the levels of corticosterone of the peripheral and adrenal venous plasma from 41±1.8 to 78±2.1 μg/100ml and from 1220±64 to 2020±56μg/ml (mean+SE) respectively. Administrations of AEAS at 3 g/kg orally or 460 mg/kg/day ip (for 6 days) also produced a marked increase. However, the increase was not detected in hypophysectomized rats. The effect of AEAS could be blocked completely by morphine in combination with pentobarbital, but not by pentobarbital alone, nor by prior injection of dexamethasone, chlorpromazine or cortisone acetate in rats under pentobarbital sodium anesthesia.We also demonstrated that in the same doses AEAS (ip) markedly increased the 5-HT content in the diencephalon of rats but not the 5-HIAA and NE contents. The action of AEAS which had been shown to result in the activation of the pituitary-adrenocortical system, was not abolished by prior treatment with reserpine at 4 mg/kg, but was completly blocked by the injection of atropine (250 μg) into the lateral ventricle of the brain. In intact rats AEAS produced a decrease of the amount of GABA in the diencephalon and significant increase of glutamine levels, while in adrenolectomized rats the effects were reversed.It is considered that the antiphlogistic effects of AEAS are due to its activation of ACh and 5-HT system and inhibition of GABA in the hypothalamus. Through the regulative action of the neurotransmitters, CRF is further activated, and, finally, it leads to the serial response of the pituitary-adrenocortical system.     

Haemoglobinuria caused by propylene glycol in sheep

Haemoglobinuria occurred in sheep anaesthetized by an intravenous injection of pentobarbitone sodium containing propylene glycol: an equivalent dose failed to cause haemoglobinuria in rabbits. Intravenous injection of an aqueous solution of 20% propylene glycol caused haemoglobinaemia and haemoglobinuria in sheep. Neither distilled water nor 20% glycerol in water administered under identical conditions produced these effects.

Haemoglobinuria occurred on some occasions when an aqueous 20% solution of propylene glycol was administered to sheep after an injection of saline: it never occurred when a solution of 20% propylene glycol prepared with physiological saline was injected. It is suggested that saline may protect against the haemolytic action of propylene glycol in sheep and that propylene glycol should be avoided as a menstruum for pharmaceutical preparations to be used for injection into the blood stream of these animals.

     

GC毛细管柱内标法测定环孢素软胶囊中乙醇与丙二醇的含量

目的采用市售GC毛细管柱替代进口注册标准中的玻璃填充柱,以正丙醇为内标、二甲基亚砜为溶剂测定环孢素软胶囊中的乙醇和丙二醇含量。方法采用正丙醇为内标,聚二甲基硅氧烷为固定相的毛细管柱(CP-SIL-5,50 m×0.53 mm,2.0μm);柱温程序升温,检测器温度(FID):250℃;载气:氮气;分流比:10∶1;进样口温度:230℃;进样量:0.2μL。结果乙醇和丙二醇质量浓度在1.5~3.5mg·mL-1范围内呈良好的线性关系,r=0.997 5~0.998 1。高、中、低3种体积分数乙醇的平均回收率为100.8%(RSD=0.9%);丙二醇的平均回收率为101.0%(RSD=0.8%)。结论该方法操作简便,能够准确测定乙醇和丙二醇的含量。     

乙醇和丙二醇单用与联用对曲安奈德喷雾溶液透皮性能的影响

目的 对曲安奈德喷雾溶液进行体外透皮试验,考察乙醇和丙二醇单用与联用时对曲安奈德喷雾溶液体外透皮功能的影响。方法 选取新西兰白兔腹部皮肤,用Franz扩散池法对曲安奈德喷雾溶液进行体外透皮试验,用高效液相色谱法（HPLC）测定曲安奈德含量,用单因素方差分析法对各组间的透皮吸收速率进行对比分析。结果 乙醇和丙二醇联用时的透皮吸收速率均显著高于单用时的透皮吸收速率（P<0.05）,且乙醇和丙二醇联用时对曲安奈德喷雾溶液的促透作用顺序为10%乙醇+25%丙二醇>10%乙醇+20%丙二醇>15%乙醇+25%丙二醇>15%乙醇+20%丙二醇。结论 10%乙醇和25%丙二醇联用时可使曲安奈德喷雾溶液的透皮功能达到最佳化。     

注射用夫西地酸钠与3种常用输液的配伍稳定性

目的考察注射用夫西地酸钠在0.9%氯化钠注射剂、5%葡萄糖注射剂及5%转化糖注射剂中的配伍稳定性。方法将注射用夫西地酸钠按临床常规用药剂量加入3种输液中,分别于25、37℃不避光条件下放置8 h,用HPLC法测定配伍后不同时间点配伍液中药物的含量,观察外观性状并测定其pH值和不溶性微粒。结果 25C时,夫西地酸钠在3种溶媒中的含量在8 h内无明显变化;37℃时,夫西地酸钠在3种溶媒中的含量在4 h内无明显变化,但8 h后明显下降(浓度下降接近或超过10%);两种温度下8 h内配伍剂的外观、pH值和不溶性微粒均无明显变化。结论注射用夫西地酸钠除了可与0.9%氯化钠注射剂、5%葡萄糖注射剂配伍外,还可与5%转化糖注射剂配伍;并且与3种输液配伍后,应置阴凉处储存,于8 h内输注完毕。     

Enhancement of transdermal delivery of progesterone using medium-chain mono and diglycerides as skin penetration enhancers

We evaluated whether medium-chain mono and diglycerides (MCG) can be utilized to optimize the transdermal delivery of progesterone (PGT). MCG was studied at 10–70% (w/w) in propylene glycol (a polar solvent) or Myvacet oil (nonpolar solvent); PGT was used at 1% (w/w). The topical (to the skin) and transdermal (across the skin) delivery of PGT were evaluated in vitro using porcine ear skin. When incorporated in propylene glycol, MCG at 10% enhanced the topical and transdermal delivery of PGT by 2.5- and 7-fold, respectively. At 20–50%, topical delivery was further enhanced while transdermal delivery gradually returned towards baseline. At 70%, MCG enhanced neither the delivery to viable skin nor the transdermal delivery of PGT. Similar concentration-dependent effects were observed when MCG was incorporated in Myvacet oil, but their magnitudes were 2- to 3-fold smaller. The relative safety of MCG was assessed in cultured fibroblasts and compared to propylene glycol (regarded as safe) and sodium lauryl sulfate (moderate-to-severe irritant). Both MCG and propylene glycol were substantially less cytotoxic than sodium lauryl sulfate. We conclude that formulations containing 10% MCG in propylene glycol may be a simple and safe method to improve the transdermal delivery of progesterone and promote its use in hormone replacement therapy.     

葛根素注射液引起急性溶血机制的实验研究

目的：探讨葛根素注射液引起急性溶血的机制。方法：用Beagle犬和豚鼠进行葛根素注射液的体内外溶血试验如下：制剂的溶媒丙二醇和pH值对体外Beagle犬红细胞的溶血作用；静脉注射葛根素对豚鼠超氧化物歧化酶（SOD）、丙二醛（MDA）的含量及致敏豚鼠红细胞溶血率的影响；葛根素对Beagle犬和豚鼠红细胞的体外溶血作用和细胞形态的影响。结果：葛根素注射液最大浓度时（10g／L）的pH值为4．48，可致Beagle犬红细胞溶血；而同pH值的0．9％氯化钠注射液未见引起Beagle犬红细胞溶血。含5％和10％丙二醇的葛根素注射液可引起Beagle犬红细胞溶血；单纯5％和10％丙二醇溶液未见引起Beagle犬红细胞溶血。豚鼠静脉注射葛根素注射液组与0．9％氯化钠组比较，红细胞膜MDA含量明显下降（P〈0．01），未见引起氧化性溶血。葛根素注射液致敏豚鼠后与致敏前比较，未见红细胞溶血率升高，未见抗原抗体复合物产生。豚鼠静脉注射葛根素注射液能引起红细胞皱缩甚至破裂。体外非免疫性溶血试验显示葛根素注射液能直接致Beagle犬和豚鼠红细胞溶血，且与剂量相关。结论：葛根素注射液引起的溶血属于药物非免疫性溶血，可能与葛根素注射液直接作用于红细胞，引起红细胞稳定性改变有关。     

Excess free energy approach to the estimation of solubility in mixed solvent systems III: Ethanol-propylene glycol-water mixtures

The reduced three-suffix solubility equation derived from the Wohl excess free energy expression is used to describe the solubility of phenobarbital in propylene glycol-water, ethanol-propylene glycol, and ethanol-water-propylene glycol mixtures and the solubility of hydrocortisone in propylene glycol-water mixtures. Solvent-solvent interaction constants were obtained by fitting total vapor pressure versus composition data, obtained at 25 +/- 0.1 degrees C, to the Wohl excess free energy model for the solvents. The equation describes solubility in these systems satisfactorily except for phenobarbital in ethanol-propylene glycol, where the solubility is fairly high and assumptions involved in the derivation of the equation do not hold.     

Effect of diclofenac and glycol intercalation on structural assembly of phospholipid lamellar vesicles

The aim of the current study was to improve the knowledge of drug–glycol–phospholipid-interactions and their effects in lamellar vesicle suitability as drug delivery systems. Liposomes were prepared using hydrogenated soy phosphatidylcholine (P90H, 60 mg/ml) and diclofenac sodium salt at two concentrations (5–10 mg/ml). To obtain innovative vesicles two permeation enhancers with glycol group, diethyleneglycol monoethyl ether and propylene glycol, were added to the water phase at different ratios (5%, 10%, and 20%).     

盐酸利多卡因凝胶剂处方优化及稳定性考察

目的:考察多种渗透促进剂对盐酸利多卡因凝胶经皮渗透的影响,并从中筛选其最佳处方组成。方法:采用离体皮肤渗透实验,以渗透速率为指标,均匀设计优化处方工艺,考察不同渗透促进剂对羧甲基纤维素钠(CMC-Na)基质的凝胶剂中利多卡因的经皮渗透效果。结果:含1.5%月桂氮(?)酮,4%聚乙二醇-400,2%泊洛沙姆和25%丙二醇(PG)的盐酸利多卡因凝胶剂具有最佳的经皮渗透速率,且处方稳定,对皮肤无刺激性。结论:渗透促进剂对盐酸利多卡因经皮渗透有显著的促进作用。