甲壳胺作为药用辅料的应用进展

甲壳胺作为药用辅料,在药剂中有多种用途,如用作粉末直接压片的崩解剂;用于生产控释固体制剂;用于改善药物的溶出;用于生产激素控释植入递药系统;透粘膜吸收促进作用等。本文综述了其应用的最新进展,并对其安全性进行了阐述。１甲壳胺的理化性质甲壳胺是由氨基葡糖和乙酰氨基葡糖聚合物组成的多糖,它可由甲壳中的甲壳素部分脱乙酰化而得到。它也在某些微生物和酵母菌中天然存在。甲壳胺一词系指一系列具有不同分子量(５０ｋＤａ～２０００ｋＤａ)、粘度和脱乙酰度(４０%～９８%)的甲壳胺聚合物。甲壳胺不溶于中性和碱性溶液,但可与无机酸和…     

甲壳质及其衍生物降低香烟焦油和烟碱含量研究

探讨了甲壳质及其衍生物在降低香烟中焦油及烟碱含量方面的作用,比较了它们添加到烟丝及醋酸纤微滤嘴中的效果,并将添加到醋纤滤嘴中的结果同英国菲尔创纳国际有限公司出品的二复合活性碳醋纤滤嘴进行了比较。微晶甲壳质(MCHI)、微晶甲壳胺(MCHS)、甲壳胺与褐藻胶复合物(CHSALG)、脂溶性甲壳胺(NBHC)、水溶性甲壳胺(NOCC)作为吸附剂添加到醋纤滤嘴中,当加量为30mg/支时,每支香烟的焦油含量分别是12.3、10.0、7.17、10.3和14.9mg;烟碱含量分别是0.74、0.68、0.64、0.69和0.7mg;过滤效率分别是35.1％、37.0％、38.5％、36.7％和33.9％。     

葛根素缓释复合骨架片理化性质的研究

目的利用甲壳胺 海藻酸钠的聚合物作为新型缓控释制剂的复合骨架材料 ,并对其性质及影响因素进行研究。方法利用天然高分子材料甲壳胺 (CS) (阳离子型 )与海藻酸钠 (AL) (阴离子型 )模拟在体内条件下形成聚电解质复合物。通过DTA及IR图谱的峰值变化证明这种复合物确实存在 ,形成的关键是控制好两种电解质的比例。结果当WCS∶WAL=2∶3时 ,反应最完全。利用制成的聚电解质复合物 ,制备葛根素缓释复合骨架片 ,缓释效果符合中国药典规定。结论甲壳胺 海藻酸钠形成的复合物可以做缓、控释制剂的骨架材料。     

甲壳胺霜(安狄菲西)治疗冻疮的疗效观察

甲壳胺(chitosan)是一种氨基多糖生化物质,本文对单方甲壳胺霜剂亦名安狄菲西的临床疗效进行了评价,临床302例冻疮患者治疗结果表明,总有效率达95％,显效率达80％,未发现任何副作用及不良反应,对各处不同程度的冻疮效果良好,且对有冻疮史的患者,提前使用尚具预防作用。     

不同介质对甲壳胺-替加氟缓释作用的影响

目的研究甲壳胺-替加氟缓释片在不同介质中的释放性质。方法以甲壳胺为辅料,采用湿颗粒法制备甲壳胺-替加氟缓释片,分别以盐酸溶液(0．1mol／L)、磷酸盐缓冲液(pH6．8)、蒸馏水为介质采用转篮法测定其释药情况,并与市售替加氟片作对比．结果甲壳胺-替加氟缓释片在0．1mol／L盐酸溶液中可持续释放达12h以上,而在蒸馏水及磷酸盐缓冲液中1h已释放达90％以上。结论甲壳胺-替加氟缓释片的缓释作用对介质pH值的依赖性较强。     

甲壳胺对人牙周膜细胞增殖和分化的影响

目的探讨甲壳胺对人牙周膜细胞增殖和分化功能的影响。方法用原代培养的人牙周膜细胞,采用MTT法、酶动力学法和放射免疫法检测不同浓度甲壳胺(Chitosan,Chi,0.05,0.1,0.2g·L-1)对人牙周膜细胞增殖、碱性磷酸酶活性和骨钙素分泌的影响。结果与对照组比较,(1)Chi(0.05g·L-1)和Chi(0.1g·L-1)2组在3,5,7d时A570值均明显升高(P<0.05),Chi(0.2g·L-1)组仅在3d时明显升高(P<0.01);(2)不论是细胞裂解液还是细胞培养液中,甲壳胺均能明显增强牙周膜细胞碱性磷酸酶活性(P<0.05);(3)不同浓度的甲壳胺刺激牙周膜细胞骨钙素分泌量均较对照组高,但只有Chi(0.1g·L-1)组比较有显著性差异(P<0.05)。结论甲壳胺对人牙周膜细胞的增殖和分化功能有明显的促进作用。     

交联甲壳胺-PEG-尼莫地平缓释颗粒性质及释药特性

目的研究交联甲壳胺PEG尼莫地平(rosslinked chitosan PEG nimodipine,RCPN)缓释颗粒的性质及体外释药特性。方法采用乳化交联法制备交联甲壳胺PEG尼莫地平缓释颗粒;用红外光谱(IR)对其结构进行表征;扫描电子显微镜(SEM)观察颗粒形态及表面结构;考察颗粒的粒径分布、颗粒中药物含量测定及在不同介质中药物的释放。结果电镜扫描显示颗粒呈球形,表面圆整,个别表面有凹凸状;RCPN缓释颗粒平均粒径为1.20 mm;红外图谱显示甲壳胺的氨基和戊二醛的羰基发生反应生成Schiffs碱。该颗粒剂有缓释作用,释药特性符合Higuchi方程。结论以交联甲壳胺做为辅料制备的缓释颗粒在体外具有缓释作用。     

国内鲜药研究的状况与展望

本文对近10年来国内鲜药的临床应用、传统保鲜方法、现代保鲜技术、鲜干药品化学成分与药效作用区别、鲜药制剂的开发应用等方面的进展加以综述,并探讨了本领域在新世纪中的发展趋势。     

甲壳胺体外对小鼠巨噬细胞PKC和DAG的作用研究

目的 观察甲壳胺体外对小鼠腹腔巨噬细胞蛋白激酶C(PKC)活性和二酰基甘油(DAG)合成的影响。方法分别采用反相离子对高效液相色谱法与放射免疫测定技术测定PKC活力和DAG含量。结果 ①甲壳胺剂量依赖性引起巨噬细胞中PKC活性明显增强并使之发生质膜转位,达峰时间为25min,1.5 h恢复到基础水平;②甲壳胺促进巨噬细胞中DAG的合成,达峰时间为30 s,3 min恢复到基础水平。结论 甲壳胺的免疫增强作用与其增强巨噬细胞中PKC活性和DAG合成有关,DAG/PKC信号途径参与了其对巨噬细胞的活化过程。     

新型缓释辅料甲壳胺的研究Ⅱ甲壳胺对不同性质药物的适应性的研究

目的：考察甲壳胺对不同性质药物的适应性。方法：选择了盐酸麻黄碱,盐酸心得安,卡马西平,磺胺嘧啶,阿司匹林,法莫替丁,扑热息痛,潘生丁,茶碱,炎痛喜康,水杨酸等不同性质的１１ 种药物,以甲壳胺为阻滞剂,制备了缓释型骨架片剂,比较其溶出效果。结果：甲壳胺的缓释作用随药物碱性增强,分子量增大,溶解度降低而增强。结论：甲壳胺对不同性质的药物均有一定缓释作用     

Effect of 1-Methylcyclopropene combined with chitosan-coated film on storage quality of passion fruit

Passion fruit is susceptible to pathogens attack and shriveling during storage. This study investigated the synergistic effect of 1-Methylcyclopropene (1-MCP) and chitosan on passion fruit. Passion Fruit treated with a combination of 1 μL/L 1-MCP and four different concentrations of chitosan solution (0, 0.5%, 1%, 1.5%, w/v), then stored at 4 °C. 1-MCP combined 1% (w/v) chitosan-coated film was more effective in improving the storage quality of passion fruit than treatment of 1-MCP combined with other concentrations of chitosan-coated. In addition, 1-MCP combined 1% (w/v) chitosan-coated film decreased the weight loss rate, shrinkage index, and respiratory rate. Furthermore, it inhibited the peroxidase (POD) and ascorbate peroxidase (APX) activity decrease. Therefore, 1-MCP combined with 1% (w/v) chitosan-coated treatment provides a new option for preserving passion fruit.     

Design of a sialylglycopolymer with a chitosan backbone having efficient inhibitory activity against influenza virus infection

We verified here the inhibitory activity of a sialylglycopolymer prepared from natural products, chitosan and hen egg yolk, against influenza virus infection and estimated the requirements of the molecule for efficient inhibition. The inhibitory activity clearly depended on two factors, the length (the degree of polymerization: DP) of the chitosan backbone and the amount (the degree of substitution: DS) of conjugated sialyloligosaccharide side chain. The inhibitory efficiency increased in accordance with the DP value, with the highest inhibitory activity obtained when the DP was 1430. The inhibition of virus infection reached more than 90% as the DS value increased up to 15.6% when the neighboring sialyloligosaccharide side chains came as close as 4 nm, which was nearly the distance between two receptor-binding pockets in a hemagglutinin trimer. These results demonstrate that the sialylglycopolymer could be an excellent candidate of the safe and efficient anti-influenza drug.     

Characterization of thermosensitive chitosan gels for the sustained delivery of drugs

The aim of this study was to investigate the physical properties of a chitosan/glycerophosphate (GP) thermosensitive solution which gels at 37 degrees C and evaluate the in vitro release profiles of different model compounds. The gelation rate was dependent on the temperature and on the chitosan deacetylation degree. The solution containing 84%-deacetylated chitosan could be stored 3 months at 4 degrees C without apparent change in viscosity. The in vitro release profiles of the model compounds depended on the presence of GP in the chitosan solution, on their molecular weight and on the presence of lysozyme in the release media. They were not affected by the electrostatic charge of the model compound when present at low concentrations. During the first 4 h, the release was accompanied by a substantial loss of the gel weight which was mainly attributed to the leaching of water and excess GP. Scanning electron micrographs revealed that the solutions yield gels with a highly porous structure after 24 h of exposure to a continuous flow of phosphate buffered saline. These results indicate that the chitosan/GP thermosensitive solutions gel rapidly at body temperature, can remain in the sol state at 4 degrees C and can sustain the delivery of macromolecules.     

硒化壳聚糖理化性质和分子结构的研究

运用高效凝胶色谱（ＨＰＧＰＣ）、乌氏粘度计、ＸＹＧ－１１０型多功能原子荧光仪、常规溶剂和ＷＺＺ－１自动指示旋光仪等方法对本实验室制备的硒化壳聚糖的理化性质进行测定,结果表明：硒化壳聚糖的分子量为３４４８;特性粘度为９９;室温干燥放置１年,硒化壳聚糖保持稳定;硒化壳聚糖在水中可溶,而且溶解度随温度升高而增加,但在有机溶剂中基本不溶;硒化壳聚糖在２５℃时的旋光度为－１４。通过紫外光谱、红外光谱、氢谱（     

EFFECT OF DELAPRIL ON THE VASCULAR ANGIOTENSIN II RELEASE IN ISOLATED HIND LEGS OF THE SPONTANEOUSLY HYPERTENSIVE RAT: EVIDENCE FOR POTENTIAL RELEVANCE OF VASCULAR ANGIOTENSIN II TO THE MAINTENANCE OF HYPERTENSION

1. In view of a recent interesting hypothesis that the vascular renin-angiotensin system (RAS) plays an important role in the maintenance of hypertension, we examined the effect of delapril (DP), a newly developed angiotensin converting enzyme inhibitor (ACEI), on angiotensin II (Ang II) release from isolated perfused hind legs of spontaneously hypertensive rats (SHR) in comparison with normotensive rats of Wistar-Kyoto strain (WKY). 2. Male SHR and WKY were given DP orally (10 mg/kg per day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was determined directly by extraction with Sep-Pak C18 cartridges connected to the perfusion system. 3. Delapril produced a sustained antihypertensive action in SHR but not in WKY. The spontaneous release of Ang II in SHR was 112.9 +/- 17.6 pg during the first 30 min of perfusion, which was somewhat greater than that in WKY (96.5 +/- 9.8 pg). An active metabolite of DP, delapril diacid (DPD), when added to the perfusion medium, suppressed the Ang II release in a dose-dependent manner in the two strains. Oral pretreatment of DP for 2 weeks suppressed the Ang II release by 60% in WKY and more pronouncedly by 73% in SHR. 4. These results suggest the presence of a functional RAS in vascular tissues which contributes to the maintenance of vascular tone of SHR, and that ACEI including DP exerts their antihypertensive effect through inhibition of vascular Ang II release in this animal model of human hypertension.     

Pharmacological studies on frozen stored canine saphenous veins and basilar arteries

Summary Canine saphenous veins were either placed in Krebs-Henseleit solution and stored for 24 h at +4°C, or immersed in FCS (fetal calf serum) containing 1.8 mol/l DMSO (dimethyl sulfoxide), slowly frozen to-70°C and stored for 4 weeks at-70°C or-190°C. Canine basilar arteries were either stored in Krebs-Henseleit solution for 24 h at +4°C or slowly frozen and stored for 3 months in FCS plus 1.8 mol/l DMSO at-70°C. Subsequent pharmacological investigations revealed a considerable attenuation of the contractile force of frozen-stored vessels but the evidence suggests that there may be a very good preservation of the main biochemical properties, such as monoamine oxidase activity, endogenous prostaglandin synthesis and uptake₁ mechanisms in veins stored at-190°C and there is an excellent correlation of thepD₂ values for various tryptamine derivatives on canine basilar arteries stored for 3 months at-70°C with those calculated on fresh preparations. It is concluded that freezing isolated blood vessels may be considered an effective means of preserving and storing vascular tissues for pharmacological investigations.     

Gene transfer with three amphiphilic glycol chitosans--the degree of polymerisation is the main controller of transfection efficiency

A number of studies have examined the possibility of delivering genes for the treatment of genetic diseases using various polymers and lipids. We have previously demonstrated the gene transfer ability of amphiphilic polymers (a soluble amine polymer covalently bound to lipid pendant groups). In the current communication we explore the gene transfer activity of amphiphilic glycol chitosans. Glycol chitosan was acid depolymerised to give polymers of various molecular weights. Palmitoyl or hexadecyl and in some cases additional N-methyl quaternary ammonium groups were attached to the polymers. DNA binding was studied by measuring the reduced fluorescence of ethidium bromide and the polyplex particle size and zeta potential. Biological characterisation of the polyplexes involved haemolysis, cytotoxicity and gene transfer assays. For the 22 polymers tested, DNA binding was optimum at a nitrogen to phosphate ratio of 2:1 and above. Polyplexes were 200-500 nm in diameter with a neutral or positive zeta potential. The haemolytic activity of the N-methyl polymers was studied and no haemolysis was detected up to a concentration of 10 mg ml-1. Cytotoxicity studies showed that the biocompatibility of glycol chitosan was adversely affected by a combination of a palmitoyl group and depolymerisation and that biocompatibility was subsequently restored with the introduction of N-methyl groups. In vitro transfection efficiency superior to the cationic lipid formulation N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulphate (DOTAP) was seen with depolymerised glycol chitosan in the A431 cell line only and with the depolymerised N-methyl quaternary ammonium amphiphilic derivatives in both the A431 and A549 cell lines. Degree of polymerisation (DP) was the most important controller of transfection efficiency and transfection resided within polymers with a DP of 73-171. High DP polymers diminished DNA-cell association, the first step in the cellular gene transfer process, thus apparently diminishing cell uptake. In vivo transfection with the N-methyl quaternary ammonium amphiphile was best at a DP of 86 and this glycol chitosan amphiphile gave superior liver and heart gene expression levels when compared to both Exgen 500 (linear polyethylenimine) and Superfect (a polyamidoamine dendrimer).     

Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum

The aim of this study was to investigate the influence of pH, buffer species and ionic strength on the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets containing chitosan and xanthan gum prepared by a hot-melt extrusion process. Drug release from hot-melt extruded (HME) tablets containing either chitosan or xanthan gum was pH and buffer species dependent and the release mechanisms were controlled by the solubility and ionic properties of the polymers. All directly compressed (DC) tablets prepared in this study also exhibited pH and buffer species dependent release. In contrast, the HME tablets containing both chitosan and xanthan gum exhibited pH and buffer species independent sustained release. When placed in 0.1N HCl, the HME tablets formed a hydrogel that functioned to retard drug release in subsequent pH 6.8 and 7.4 phosphate buffers even when media contained high ionic strength, whereas tablets without chitosan did not form a hydrogel to retard drug release in 0.1N HCl. The HME tablets containing both chitosan and xanthan gum showed no significant change in drug release rate when stored at 40 °C for 1 month, 40 °C and 75% relative humidity (40 °C/75% RH) for 1 month, and 60 °C for 15 days.     

溶剂抽提法分离胺类药物的研究

溶剂分次抽提法优点很多,若能使分配率差别大,则可用来分离药物混合物。本研究以测定分配率作依据,找寻分离溶剂与条件。检样以叔胺为主。先试验了药物在1N盐酸溶液中对14种有机溶剂的分配率。选择烷烃、醚、酮、醇、卤代烃五类溶剂,测定药物在不同pH值水溶液时的分配率。进而研究了卤代烃类对叔胺的分配率。初步找出一些规律。知分配率与溶剂的介电常数成规律关系。叔胺药物的分配率依水相pH值而有规律变化。可利用在某一pH值水溶液时,各药分配率的不同而抽提分开。应用此法分离,分光光度等法定量,测定了7个3至5种药混合的药物混合物。变量系数最大为±1.6%。此外,还研究了温度对分配率的影响,及分配率与纸层析的关系。在酸性水溶液中,多数有机溶剂也能抽提出叔胺类药物。     

Determination of DP‐VPA and its active metabolite,VPA, in human plasma,urine, and feces by UPLC–MS/MS: A clinical pharmacokinetics and excretion study

DP‐VPA is a phospholipid prodrug of valproic acid (VPA) that is developed as a potential treatment for epilepsy. To characterize the pharmacokinetics and excretion of DP‐VPA, four reliable ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) methods were validated for quantitation of DP‐VPA and its metabolite, VPA, in human plasma, urine, and feces. Protein precipitation and solid‐phase extraction (SPE) were used for extraction of C16, C18 homologs of DP‐VPA and VPA, respectively, from plasma. Urine and fecal homogenate involving the three analytes were efficiently prepared by methanol precipitation. The determinations of C16 DP‐VPA, C18 DP‐VPA, and VPA were performed using the positive multiple reaction monitoring (MRM) mode and the negative single ion monitoring (SIM) mode, respectively. The analytes were separated using gradient elution on C8 or phenyl column. Satisfactory results pertaining to selectivity, linearity, matrix effect, accuracy and precision, recovery, stability, dilution integrity, carryover, and incurred sample analysis (ISR) were obtained. The calibration ranges in human plasma were as follows: 0.00200–1.00 μg/mL for C16 DP‐VPA, 0.0100–5.00 μg/mL for C18 DP‐VPA, and 0.0500–20.0 μg/mL for VPA. The linear ranges in urine and fecal homogenate were 0.00500–2.00 μg/mL and 0.00200–0.800 μg/mL for C16 DP‐VPA, 0.00500–2.00 μg/mL and 0.0100–4.00 μg/mL for C18 DP‐VPA, and 0.200–80.0 μg/mL for VPA, respectively. The intra‐ and inter‐batch coefficients of variation in three matrices ranged from 1.7% to 12.4% while the accuracy values ranged from 85.4% to 111.7%. The developed methods were successfully applied to determine pharmacokinetics of DP‐VPA tablet after a single oral dose of 1200 mg in 12 healthy Chinese subjects under fed condition.