新型水包油佐剂SP01的安全性评价

目的通过动物实验评价新型水包油佐剂SP01的安全性。方法通过昆明小鼠安全药理试验、昆明小鼠急性毒性试验、Hartley豚鼠过敏反应试验、溶血性试验、日本大白兔局部刺激性试验、SD大鼠长期毒性试验及BALB/c小鼠致突变、致畸、致瘤试验,对水包油佐剂SP01的安全性进行全面评价。结果水包油佐剂SP01对昆明小鼠的自主活动无明显影响;急性毒性试验中可观察到水包油佐剂SP01组昆明小鼠给药后无死亡,体重明显增加,且各组织器官无病理变化;水包油佐剂SP01注射豚鼠未见任何过敏反应及症状;溶血性试验结果显示,水包油佐剂SP01在体外对兔红细胞无溶血作用,不引起红细胞凝聚;将水包油佐剂SP01经日本大白兔耳缘静脉注射连续刺激5 d后,佐剂组与氯化钠注射液组家兔耳缘静脉给药部位肉眼观察均无明显变化,病理切片显微镜观察均未见炎性浸润、血管周围组织出血及坏死等刺激现象;将水包油佐剂SP01经肌肉连续注射大鼠1个月,佐剂组大鼠体重明显增加,精神状态、食欲、睡眠情况与氯化钠注射液组无明显差异,停药后连续观察3个月,大鼠精神状态、食欲、睡眠情况均良好;将水包油佐剂SP01连续经BALB/c小鼠腿部肌肉注射14 d后,其肌肉组织病理切片显示,与氯化钠注射液组小鼠的肌肉组织无明显差异。结论水包油佐剂SP01对实验动物无急性毒性、过敏反应、局部性刺激、长期毒性及致突变、致畸、致瘤作用,是安全、可应用的油类佐剂,本研究为该系列水包油佐剂的临床应用提供了实验依据。     

鱼金注射液对试验动物神经系统影响的研究

目的观察肌肉注射鱼金注射液对实验动物神经系统影响,为评价鱼金注射液的用药安全性提供实验依据。方法单性肌肉注射8mL/kg、4mL/kg、2mL/kg剂量的鱼金注射液(相当于临床用量的30、15、7.5倍)。通过GJ-I光电计数仪观察药物对小鼠自主活动的影响,爬杆法观察药物对小鼠协调运动的影响。结果鱼金注射液三个剂量组对于小鼠的自主活动、一般状态、爬杆时间变化率与生理盐水组相比均无明显差异,对于戊巴比妥钠阈下催眠作用与生理盐水(NS)组相比亦无统计学差异。结论肌肉注射鱼金注射液,对小鼠的神经系统无明显影响。     

人用重组禽流感血凝素疫苗接种大鼠的安全性及免疫原性

目的评价家蚕生物反应器生产的重组禽流感血凝素疫苗的安全性和免疫原性。方法将SD大鼠随机分为5组,分别经皮下注射9.4、1.88和0.375mg/kg剂量的重组禽流感血凝素疫苗(含氢氧化铝佐剂)、A(lOH)3和生理盐水,每10d注射1次,连续注射3次,分别于第1次给药后第2、22和42天进行血液学、血液生化学、病理学和免疫原性检测。结果3个剂量组疫苗第1次给药后第42天,检测抗体滴度(P/N)在8～11之间,CD4+、CD8+T淋巴细胞含量及IFNγ和IL-2的含量与两对照组相比,未见明显升高;连续3次给药后,大鼠的血液学和生化学指标均无明显改变;给药期间注射部位皮下出现肉芽肿样结节,经20d恢复后有所改善;9.4和1.88mg/kg剂量组动物出现可逆性的脾肿大症状;整个实验期间,动物未出现任何其他明显不良反应。结论重组禽流感血凝素疫苗对大鼠具有良好的安全性,但免疫原性较低。     

壳聚糖季铵盐微球作为注射疫苗佐剂的安全性评价

以小鼠、大鼠、豚鼠、家兔等为动物模型,对壳聚糖季铵盐微球作为注射疫苗佐剂进行安全性评价. 结果表明,小鼠急性毒性实验中50倍临床拟给药剂量(5.0 mg/只)下动物耐受性良好;大鼠重复毒性实验中即使50倍高剂量多次注射微球,动物各组织器官仍无病理性变化;异常毒性实验中小鼠给药后体征正常、体重明显增加,壳聚糖微球注射豚鼠后未见过敏反应及症状;家兔注射部位未发生肌肉组织溃烂、化脓等,佐剂未引起红细胞溶血.     

艾纳香口腔护理液安全性评价研究

选用SD大鼠进行口腔黏膜刺激性试验、口腔及黏膜用药急性毒性试验;选用白色豚鼠进行过敏试验;选用昆明种小鼠进行灌胃给药急性毒性试验,观察给药后动物口腔黏膜、受药皮肤、体重变化、全身毒性反应情况及死亡只数。艾纳香口腔护理液在口腔黏膜刺激性试验中,未发现SD大鼠口腔黏膜组织异常;在过敏试验中,白色豚鼠皮肤用药未引起过敏反应;在急性毒性试验中,大鼠的耐受性良好;小鼠灌胃时测得的最大给药量(MLD)为288 mg/kg,相对于成人给药量的1 200倍。上述动物均未见死亡和明显毒性反应。以上试验说明艾纳香口腔护理液无口腔黏膜刺激性和致敏性,无明显急性毒性反应,提示其作为口腔外用护理液临床用药安全。     

丹参注射液对慢性胰腺炎的治疗作用

目的探讨丹参注射液对慢性胰腺炎大鼠血清中HA和LN的影响,从而验证丹参注射液对慢性胰腺炎的治疗作用。方法通过胰管内注射2%三硝基苯磺酸的方法建立大鼠慢性胰腺炎纤维化模型。50只雄性SD大鼠随机分成5组:正常组、模型组、丹参小剂量组(400mg/kg)、丹参中剂量组(800mg/kg)、丹参大剂量组(1600mg/kg)。4周后应用免疫组化法(ELLSA)检测大鼠血清中的HA和LN的表达情况,同时将胰腺组织行HE染色,观察病理形态学改变。结果模型组发生明显的胰腺纤维化,血清中的HA和LN的表达明显升高。各不同剂量干预组纤维化程度及HA和LN的表达均低于模型组。结论丹参注射液可抑制大鼠胰腺纤维化组织的形成,对慢性胰腺炎有一定的治疗作用。     

唑菌酯原药大鼠致畸毒性试验

[目的]测定唑菌酯原药对大鼠致畸方面的影响。[方法]应用Sprague Dawley(SD)大鼠为试验动物,设计5、15、45 mg/kg b.w.3个剂量组和1个阴性对照组来测定唑菌酯原药对动物致畸的影响。[结果]大鼠经口灌胃给予唑菌酯原药15、45 mg/kgb.w.两个剂量组动物和对照组动物相比,出现显著性的体质量增长缓慢;各剂量组胎鼠体质量也出现增长缓慢。[结论]经口灌胃给药15 mg/kgb.w.时,对孕鼠体质量增长有影响;给药5 mg/kg时,对胎仔的生长速度有影响;但并无致畸作用。     

98%螺螨酯原药对大鼠生殖方面的影响

[目的]以Sprague Dawley(SD)大鼠为试材,进行98%螺螨酯原药大鼠的生殖毒性试验。测定98%螺螨酯原药对动物繁殖和致畸方面的影响。[方法]分别通过大鼠的繁殖试验和致畸试验来确定98%螺螨酯原药对动物繁殖和致畸的影响。[结果]98%螺螨酯原药对大鼠2代繁殖试验:对大鼠系统毒性的最小有作用剂量为530 mg/kg饲料,对大鼠的生殖毒性最小有作用剂量为530 mg/kg饲料,对子代生长发育的最小有作用剂量为4 800 mg/kg饲料。98%螺螨酯原药对大鼠致畸试验:98%螺螨酯原药对母鼠的最大无作用剂量为480 mg/kg,对胎鼠的最大无作用剂量为480 mg/kg。[结论]98%螺螨酯原药对大鼠繁殖试验有一定影响,而对母鼠胚胎毒性和胎鼠生长发育没有明显影响。     

注射用呋异丙苷的安全性实验

目的　观察注射用呋异丙苷的安全性。方法　选取NIH小鼠、新西兰兔和豚鼠分别进行急性毒性试验、过敏试验、肌肉刺激试验、血管刺激试验及溶血性试验。结果　呋异丙苷无过敏反应和溶血现象 ,对静脉血管及肌肉无刺激反应 ,NIH小鼠经尾静脉及腹腔注射LD50 分别为 130 9.2mg/kg和 170 7.4mg/kg。结论　注射用呋异丙苷是安全的     

马蹄香对小鼠的急性毒性及对大鼠的亚急性毒性观察

目的观察马蹄香(Valeviana jatamansi Jones)对小鼠的急性毒性及对大鼠的亚急性毒性,以评价其安全性。方法给小鼠灌服5 000、7 500、10 000 mg/kg的马蹄香,对照组灌胃1%羧甲基纤维素钠(CMC),观察小鼠的中毒症状,记录小鼠的死亡数,采用Red-Munchen法计算半数致死量(LD50),并检查小鼠组织和脏器的病理变化;对大鼠分别灌服4 000、1 000和200 mg/kg的马蹄香,连续给药14 d,对照组灌胃CMC水溶液,给药后观察14 d,检测大鼠体重、脏器系数、血常规指标、血生化指标及组织病理变化情况。结果急性毒性试验结果显示,灌胃马蹄香后,小鼠短时间内出现活动减少,而后趋于正常,病理学检测未发现小鼠组织或脏器有明显异常改变,LD50>10 000 mg/kg;亚急性毒性试验结果显示,马蹄香各剂量组大鼠的增重、脏器系数、血常规指标、血生化指标及组织病理变化与对照组比较,差异均无统计学意义(P>0.05)。结论马蹄香具有较好的安全性。     

Synthesis and anticoagulant activity of pectin sulfates

In this article, we describe the first use of trisulfonated sodium amine as a sulfating reagent for preparing pectin sulfate in aqueous solution. The main reaction parameters that were expected to affect the degree of substitution (DS) were studied. The optimal reaction conditions for the synthesis of pectin sulfate were found to be as follows: the pH of the reaction medium, the reaction temperature, the reaction time, and the ratio of the mole of sodium nitrite (n_NaNO2) to the mass of pectin (m_pectin) were 6, 60°C, 12 h, and 2.5/190 mol/g, respectively. Pectin and pectin sulfate were characterized by Fourier transform infrared (FTIR) spectroscopy and ¹³C‐NMR. The FTIR spectra showed the characteristic absorptions of sulfate ester bonds at 1264 and 830 cm^?1. Furthermore, the anticoagulant activity of pectin sulfates with different DSs, concentrations, and molecular weights were investigated with respect to the activated partial thromboplastin time (APTT), thrombin time (TT) and prothombin time. The clotting assay indicated that the pectin sulfate prolonged APTT and TT through inhibition of the activity of antithrombin. These results suggest that the introduction of sulfate groups into the pectin structure improved its anticoagulant activity. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

抗凝血硫酸化微晶纤维素的制备

以微晶纤维素(MC)为原料,采用氯磺酸-DMF硫酸化方法制备了具有抗凝血活性的硫酸微晶纤维素钠盐Na-MCS,并研究了以提高产物抗凝血活性为目标的工艺,即在常温条件下向原料MC中加入适量的浸润试剂DMF,并在真空下搅拌浸润;在盐水冰浴中制备氯磺酸-DMF酯化试剂;将适量酯化试剂加入已浸润的MC中搅拌反应;调节反应产物的pH值,在去离子水中透析,减压浓缩后真空干燥。     

Rational design of anticoagulant drugs using oligosaccharide chemistry

For a long time, heparin and low molecular weight heparins have been the drugs of choice for the management of thrombosis. Discovery of the antithrombin binding domain in heparin, a critical element in the anticoagulant activity of this polysaccharide, allowed a rational approach based on medicinal carbohydrate chemistry in the design of new anticoagulants. The fully synthetic pentasaccharide fondaparinux that selectively targets blood coagulation factor Xa was first to be developed as a drug. Fondaparinux was followed by various heparin mimicking oligosaccharides prepared with a view to replace polydisperse heparin and low molecular weight heparins by structurally-defined anticoagulants with no unwanted side-effects.     

Hirudin as an anticoagulant for both haematology and chemistry tests

Hirudin, an extract from the leech, has powerful antithrombin activity affecting the blood coagulation pathway. We evaluated the usefulness of hirudin in anticoagulating specimens for routine laboratory tests. Results using blood anticoagulated with hirudin corresponded well with results with blood treated with ethylenediamine tetraacetic acid (EDTA) in the complete blood count (CBC), including white blood cell (WBC) differential count and morphology of blood cells, when CBC was performed within 2 h of blood collection. Clinical chemistry results from hirudin-treated samples were similar to results obtained with serum specimens. Thus, hirudin may be a useful anticoagulant for emergency laboratory medicine.     

Sulfation of silk fibroin by sulfuric acid and anticoagulant activity

Silk fibroin (Bombyx mori) was sulfated with an aqueous sulfuric acid solution. The sulfated fibroin was characterized by Fourier transform infrared spectroscopy (FTIR), amino acid analysis, and gel filtration chromatography (GFC). Maximum yield was obtained at around 2–4 h, and it decreased at 6 h and more. The molecular size decreased and dispersed with sulfation, and the molecular weight was estimated at around 10,000 by GFC using protein standards. The amino acid composition indicated that the crystal region of the fibroin molecule remained in sulfated fibroin until a sulfation reaction time of 4 h. The incorporation of sulfate groups was confirmed by FTIR and the amount of sulfate groups introduced for 4 h sulfation was estimated in 0.3 mmol/g by acidimetric titration. The efficiency of sulfation was calculated at 15.7%. Blood coagulation was prevented by 20 mg of sulfated fibroin in 1 mL of blood, while original fibroin did not show the effect. This result indicates that sulfate group introduction results in addition of anticoagulant function to silk fibroin. Although a variety of polymer backbones have been used for synthesis of sulfated polymers as anticoagulant materials, no reports are available concerning a sulfated polymer based on a protein backbone. Sulfated fibroin is a new type of anticoagulant material having a protein backbone. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 2377–2382, 2003     

Synthesis,characterization, and anticoagulant activity of carboxymethyl starch sulfates

To develop a renewable and compatible anticoagulant as potential heparin alternative, carboxymethyl starch sulfate (CMSS) was prepared by the reaction of carboxymethyl starch (CMS) and sulfating reagent [N(SO₃Na)₃]. The chemical structures of CMS and CMSS were characterized by Fourier transform infrared spectroscopy and ¹³C nuclear magnetic resonance. The influences of reaction parameters, including the pH of sulfating reagent, the molar ratio of sulfating reagent to CMS, reaction time, and temperature on the degree of substitution of sulfate groups (DS) of CMSS were studied. Meantime, the DS of each CMSS was determined by barium sulfate–glutin nephelometery method. Moreover, the anticoagulant activity of CMSS was investigated by the coagulation assays of activated partial thromboplastin time, thrombin time, and prothrombin time. The results revealed that the anticoagulant activity of CMSS was closely related to the DS value and concentration. The anticoagulant activity was promoted with the increasing of the DS and concentration. The molecular weight (M_w) in measured range had little impact on anticoagulant activity in contract to the DS and concentration. In this article, the CMSS with the DS of 1.91, concentration of 75 μg/mL and the M_w of 2.61 × 10⁴ had the best blood anticoagulant activities. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

纳米ZnO改性聚酯抗凝血性能研究

采用原位聚合方法制备了纳米ZnO/聚酯复合物,采用热压成膜和溶液法成膜两种方法将其制膜,利用动态凝血实验研究了纳米ZnO添加量及成膜方法对聚酯抗凝血性能的影响。结果表明,溶液法成膜的薄膜抗凝血性能优于热压法成膜。含有纳米ZnO的聚酯薄膜的抗凝血性能优于纯聚酯薄膜。随着纳米ZnO的加入量不断增加,聚酯薄膜的抗凝血性能先增加后减少。     

抗凝冰沥青路面在泰山景区天外村旅游公路的应用

该项目属于旅游公路范畴,位于泰山景区内,属于盘山公路,具有海拔高、纵坡大、转弯半径小,昼夜温差大、常年气温低等特点。面层采用SMA-10路面结构,首先确定未添加抗凝冰材料的最佳级配及沥青用量,其次采用抗凝冰材料等效替代5%的矿粉用量,并进行路用性能试验,试验结果均能满足要求。进行实体路面铺筑,对施工工艺进行补充完善,整体路面检测指标优良,满足规范要求。     

Preparation and anticoagulant property of phosphorylcholine‐terminated o‐benzoylchitosan derivative

To improve the solubility in organic solvent of chitosan, o‐benzoylchitosan was synthesized by acylation with benzoyl chloride and then used in the reaction with 2‐chloro‐1,3,2‐dioxaphosphospholane (COP) to prepare phosphorylcholine‐terminated o‐benzoylchitosan (PC‐BCS). PC‐BCS had a structure with a phospholipid polar group characterized by FTIR and ¹H NMR. PC‐BCS had been polysubstituted by a PC group, which made PC‐BCS viscous liquid. The anticoagulant properties of PC‐BCS were evaluated by means of blood‐clotting and platelet adhesion assay. The blood‐clotting assay indicated that PC‐BCS could prolong the blood‐clotting process. Platelet adhesion assay showed that PC‐BCS could effectively inhibit the platelet adhesion and activation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 489–493, 2003