Kanamycin incorporation in lipid vesicles prepared by ethanol injection designed for tuberculosis treatment

The primary goal of this study was the production of liposomes encapsulating kanamycin for drug administration by inhalation. The selected drug is indicated for multiresistant tuberculosis, and administration through inhalation allows both local delivery of the drug to the lungs and systemic therapy. The ethanol injection method used for the liposome production is easily scaled up and is characterized by simplicity and low cost. Vesicles were prepared using different lipid compositions, including hydrogenated soybean phosphatidylcholine and cholesterol (SPC/Chol), egg phosphatidylcholine and cholesterol (EPC/Chol), distearoyl phosphatidylcholine and cholesterol (DSPC/Chol), distearoyl phosphatidylcholine, dimyristoyl phosphatidylethanolamine and cholesterol (DSPC/DMPE/Chol), dipalmitoyl phosphatidylcholine and cholesterol (DPPC/Chol) and dipalmitoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol and cholesterol (DPPC/DPPG/Chol). The effects of different operational conditions for vesicle production and drug encapsulation were evaluated, aiming at a compromise between final process cost and suitable vesicle characteristics. The best performance concerning drug incorporation was achieved with the DSPC/Chol system, although its production cost was considerably larger than that of the natural lipids formulations. Encapsulation efficiencies up to 63% and final drug to lipid molar ratios up to 0.1 were obtained for SPC/Chol vesicles presenting mean diameters of 132 nm incubated at 60 degrees C with the drug for 60 min at an initial drug-to-lipid molar ratio of 0.16.     

Memory facilitation by post-training injection of ethanol

Immediate post-training IP injection of ethanol (0.75–4.5 g/kg) significantly enhanced retention of a one-trial passive avoidance task in mice compared to saline controls. Ethanol (4.5 g/kg) in the absence of footshock did not affect test performance. The memory facilitation may reflect ethanol's effects on neurotransmitter, macromolecular, or hormonal systems, or a reduction in interference.     

Gastroresistant capsular device prepared by injection molding

In the present work, the possibility of manufacturing by injection molding (IM) a gastro-resistant capsular device based on hydroxypropyl methyl cellulose acetate succinate (HPMCAS) was investigated. By performing as an enteric soluble container, such a device may provide a basis for the development of advantageous alternatives to coated dosage forms. Preliminarily, the processability of the selected thermoplastic polymer was evaluated, and the need for a plasticizer (polyethylene glycol 1500) in order to counterbalance the glassy nature of the molded items was assessed. However, some critical issues related to the physical/mechanical stability (shrinkage and warpage) and opening time of the device after the pH change were highlighted. Accordingly, an in-depth formulation study was carried out taking into account differing release modifiers potentially useful for enhancing the dissolution/disintegration rate of the capsular device at intestinal pH values. Capsule prototypes with thickness of 600 and 900 μm containing Kollicoat^® IR and/or Explotab^® CLV could be manufactured, and a promising performance was achieved with appropriate gastric resistance in pH 1.2 medium and break-up in pH 6.8 within 1 h. These results would support the design of a dedicated mold for the development of a scalable manufacturing process.     

The suppression of ethanol self injection by buprenorphine

The schedule induced self-injection procedure was used to establish ethanol self-injection in 16 rats. Pretreatment with an injection of 0.3 mg/kg buprenorphine significantly reduced ethanol self-injection in a group of 8 rats. This effect was not found in a second group of 8 rats which received saline pretreatment. The findings provide support for an involvement of buprenorphine, in ethanol self-injection, which cannot be explained in terms of opiate induced shifts in taste preference. From the present data it cannot be determined whether the agonist or antagonist opiate properties of buprenorphine cause the blocking effect.     

醒脑静注射液对乙醇所致记忆功能障碍的影响

目的 :观察醒脑静注射液 (Xnji)对乙醇所致记忆障碍的改善作用。方法 :乙醇一次给大鼠和小鼠灌服和连续灌服造成学习记忆功能障碍 ,学习记忆的测试采用Morris水迷宫法 ,电迷宫法和避暗法。结果 :Xnji 1.4 ,0 .7ml·kg-1可预防一次性灌服乙醇所致的大鼠空间辨别障碍 ;Xnji 1,2ml·kg-1可治疗连续灌服乙醇所致的小鼠空间辨别障碍和记忆获得障碍。结论 :Xnji可防治急、慢性乙醇中毒所致的学习记忆功能减退。     

Enzymatic determination of ethanol in saliva by flow injection analysis

Enzymatic photometric and fluorimetric methods are proposed for the determination of ethanol in saliva with determinative ranges of 2.5-15.0 mug ml(-1) and 1.0-20.0 mug ml(-1) respectively, i.e. covering the legal ranges after 1 : 100 dilution. A comparison between the ethanol content in saliva, breath and blood has been carried out on 12 individuals; the determination in saliva has been shown to be a good option.     

乙醇注入法制备柚皮素脂质体及其质量评价

目的制备柚皮素脂质体,优化其处方和工艺,并对其相关性能进行评价。方法采用乙醇注入法制备柚皮素脂质体,通过正交设计优化处方工艺;利用马尔文动态光散射粒径测定仪测定其zeta电位和粒径,采用微型凝胶柱离心法分离游离药物和脂质体,HPLC法测定脂质体中柚皮素的包封率。结果确定最佳处方为:磷脂的质量浓度为0.006 g·m L~(-1),胆固醇与磷脂的质量比为1∶3,药脂比为1∶20,缓冲液p H值为7.40,类脂溶液的溶解温度设定为55℃,类脂溶液的溶解时间为25 min。制得的柚皮素脂质体包封率为(80.44±0.98)%,平均粒径为(223±11)nm,Zeta电位为(-35.9±5)m V。结论乙醇注入法制备柚皮素脂质体工艺简单可行,所制备的柚皮素脂质体包封率高、粒径较小、稳定性好。     

Preparation and characterization of etoricoxib-beta-cyclodextrin complexes prepared by the kneading method

The binary system of etoricoxib with beta-cyklodextrin (beta-CD) was prepared by the kneading method. Drug-cyclodextrin interactions in solution were investigated by the phase solubility analysis. Differential scanning calorimetry, infrared spectroscopy, powder X-ray diffractometry and microscopic study were used to characterize the solid state of all binary systems, whereas their dissolution properties were evaluated according to the USP XXIII paddle method. The results indicate partial interaction of the drug with beta-CD in the physical mixture and complete interaction in the kneaded complex. The dissolution of etoricoxib was notably increased as compared to pure drug as well as its physical mixture. The complex showed more than 75% drug released in 30 min.     

Preparation of immuno-stimulating complexes (ISCOMs) by ether injection

This study investigated the application of the solvent dispersion technique, specifically ether injection, which has been successfully used in the preparation of liposomes, as a new, continuous and potentially scaleable method for the preparation of ISCOMs. Phosphatidylcholine (PC) and cholesterol (Chol) were dissolved in ether, which was injected into an aqueous solution, maintained at 55 °C, containing Quil A. The influences of the following variables on ISCOM formation were investigated: ratio of PC:Quil A:Chol used, pumping rate, total lipid mass and concentration of buffer salts and Quil A in the aqueous phase. All samples were characterized by negative stain transmission electron microscopy, photon correlation spectroscopy and sucrose ultracentrifugation gradient. It was demonstrated that ISCOMs could be produced by this method but the homogeneity of the preparation was influenced by the conditions used. Homogeneous ISCOM preparations were consistently produced only when the weight ratio of PC:Quil A:Chol was 5:3:2 with a total lipid mass of 20 mg, the Quil A dissolved in a 0.01 M phosphate buffer at a concentration of 6 mg in 4 ml, and the ether solution injected into the warmed buffer solution at a rate of 0.2 ml/min. Changing any of these variables resulted in more heterogeneous preparations in which ISCOMs typically co-existed with other colloidal structures such as worm-like and helical micelles, liposomes, lamellae and lipidic particles.     

反相高效液相色谱法测定参附注射液及市售黑附片中乌头碱的含量

目的　测定参附注射液及市售黑附片中乌头碱的含量。方法　用RP HPLC ,流动相为乙腈 醋酸铵缓冲液 (pH10 5 ) ,紫外检测波长 2 3 0nm ,流速 0 8ml·min-1。结果　对照品的线性范围 1 3 9～ 2 2 2 4 μg(r =0 9997) ;市售黑附片中的乌头碱比参附注射液中的高 3倍。结论　方法简便、快速、准确、重现性好 ,可以作为样品的检验方法     

Comparative study of autologous fibrin glues prepared by cryo-centrifugation, cryo-filtration, and ethanol precipitation methods

To establish a speedy preparation method for the fibrinogen-rich fraction (FRF) from autologous plasma using fibrin glue, we compared the concentrations and yields of coagulation factors in FRF prepared by 3 methods. Human plasma from healthy volunteers was divided into 3 samples. Two samples were frozen at -20 degrees C in a freezer and defrosted in a 4 degrees C water bath. One sample of defrosted plasma was centrifuged and FRF was obtained (C method). Another sample of defrosted plasma was filtered and FRF was obtained (F method). The last sample was treated with cold ethanol(1/10) in a 4 degrees C water bath and FRF was obtained after centrifugation (E method). The concentrations of fibrinogen, fibronectin, factor XIII, and plasminogen in each obtained FRF were measured and yields were calculated. (1) The volume of FRF obtained by the E method was greater than that by the C method, but less than that by the F method. While the variation in volume obtained by the E method was the lowest among the 3 methods; (2) the concentrations of fibrinogen obtained by the E and C method were similar, but the yield from the E method was the highest; (3) the concentration and yield of fibronectin from the E and C method were similar and were greater than those by the F method; (4) the concentration and yield of factor XIII from the E method were significantly higher than those from the other methods; (5) the E method preparation time was about 1 h, the shortest among the 3 methods. These results indicate that high quality FRF from autologous plasma can be prepared easily and within 1 h by the E method.     

Physicochemical properties of antifungal drug–cyclodextrin complexes prepared by supercritical carbon dioxide and by conventional techniques

Antifungal drugs are the most common systemic drugs used for the treatment of oropharyngeal candidiasis, which is the first symptom of HIV infection. However, the efficacy and bioavailability of these drugs have been limited by their poor aqueous solubility and dissolution rate. Therefore, the aim of this study was to investigate the effect of different preparation methods (i.e. kneading, coevaporation, sealed-heating, and a solid inclusion technique using supercritical carbon dioxide carrier (SC CO₂-inclusion)) for obtaining solid inclusion complexes between β-cyclodextrin and three antifungal drugs (itraconazole, econazole, and fluconazole). The physicochemical properties of the different products were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffractometry (PXRD). For the complexes prepared by the SC CO₂-inclusion method, the effects of temperature and pressure have also been investigated.     

聚乙二醇重组人粒细胞集落刺激因子对局部注射乙醇诱发的急性、局限性兔肝损伤的治疗作用

目的:研究聚乙二醇重组人粒细胞集落刺激因子(PEG-rhG-CSF)抗肝损伤的作用。方法:用乙醇局部注射诱发急性、局限性肝损伤模型,以血清谷胱甘肽-S-转移酶(GST)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总蛋白(TP)和白蛋白(ALB)的含量、肝脏指数、肝脏坏死范围、炎症程度、肝细胞增殖指数为指标,观察PEG-rhG-CSF(10μg·kg~(-1),im,qd,q2d和q4d,疗程14d)抗肝损伤的作用。结果:与模型组比较,PEG-rhG-CSFqd,q2d和q4d组均明显降低血清GST含量,差异显著(P<0.05),但各组间无明显差别;PEG-rhG-CSF q4d组坏死区域明显减小(P<0.05),q2d组和qd组坏死区域极显著减小(P<0.01);PEG-rhG-CSF q2d组和qd组炎性程度显著减轻;PEG-rhG-CSF q4d组肝组织5-溴脱氧尿嘧啶(BrdU)标记指数显著增加(P<0.05),q2d组和qd组极显著增加(P<0.01)。已知保肝药联苯双酯亦有显著效果。结论:PEG-rhG-CSF对局部注射乙醇诱发的急性局限性兔肝损伤有明显的治疗作用。     

不同工艺制备的静注人免疫球蛋白产品质量对比研究

目的 对比用低温乙醇蛋白分离工艺制备的静注人免疫球蛋白（pH4）和两步阴离子交换层析制备的静注人免疫球蛋白（10%）产品质量指标,分析制备工艺对产品质量的影响。方法 对2种工艺的产品进行IgA含量、分子大小分布、抗-HBs效价、蛋白空间结构、Fc片段活性、抗体谱和IgG亚型分布等指标的检测和对比分析。结果 两步阴离子交换层析制备的静注人免疫球蛋白的IgA含量（5.30 μg/ml）明显低于低温乙醇分离制备的（281.95 μg/ml）,而分子大小分布、抗-HBs效价、蛋白空间结构、Fc片段活性、抗体谱、亚型分布指标没有明显差别。结论 两步阴离子交换层析制备的静注人免疫球蛋白（10%）具有更高的安全性。     

注射用环糊精包合物研究进展

传统注射剂中对于难溶性药物采用的增溶手段多为添加有机助溶剂或表面活性剂,其刺激性易导致疼痛、炎症等多种不良反应。环糊精(cyclodextrin, CD)是一种具有空穴的环状低聚糖,部分天然环糊精及其衍生物具有良好的水溶性和生物相容性,可以通过包合作用增加难溶性药物的溶解度及稳定性,且降低对注射部位的刺激,是注射剂中增溶剂的更优选择。本文对环糊精在已上市注射剂产品中的应用及其发展前景进行综述,为环糊精在注射剂中更广泛的应用发展提供参考。     

A method for the incorporation of ovalbumin into immune stimulating complexes prepared by the hydration method

This study describes the development of a method for the incorporation of fluorescently labelled ovalbumin (FITC-OVA) into immune stimulating complexes (ISCOMs) prepared by the hydration method. Conjugation of palmitic acid was performed to fluorescently labelled OVA (pFITC-OVA) or to non-labelled OVA, with subsequent conjugation of FITC to the resulting palmitified OVA (FITC-pOVA). Both pFITC-OVA and FITC-pOVA, but not FITC-OVA, could be incorporated into ISCOMs and other non-liposomal colloidal structures. The degree of incorporation of pFITC-OVA or FITC-pOVA in non-liposomal colloidal particles reaches a maximum, if ISCOMs are the predominant colloids in the system.     

B超导向无水乙醇注射治疗复发性甲状腺囊肿的疗效观察

目的　探讨B超导向经皮无水乙醇注射 (PEI)治疗复发性甲状腺囊肿的安全性、有效性及临床应用价值。方法　PEI治疗 32例复发性甲状腺囊肿 ,按穿刺出囊液量的 1/ 3注入无水乙醇 ,每周 1次 ,平均 2～ 7次。结果　PEI治疗后甲状腺囊肿容积显著缩小 ,平均 (79 5± 3 6 ) % ,有效率达 90 6 %。随访 2年 ,无一例复发 ,囊肿平均缩小 (91 1± 2 1) % ,有效率增至 10 0 %。未见明显不良反应。结论　PEI治疗复发性甲状腺囊肿是一种安全、有效的非手术疗法。     

无水乙醇淋巴结注射对肺部恶性肿瘤转移的影响

目的　探讨无水乙醇顺行性淋巴结封闭对肺部恶性肿瘤转移的影响。方法　随机选择72例肺癌患者在术中按照Naruke 肺癌淋巴结分布图, 用无水乙醇注射该病种最易转移的区域淋巴结。另选择TNM相似的肺癌患者, 采用常规手术方法进行手术。术后复查血液中乙醇含量、肝功及复查CT了解注射淋巴结肿大情况, 对两组病例进行统计分析。结果　全组无手术死亡。术后血常规、肝功能、免疫球蛋白等均未见明显异常, 两组乙醇含量比较差异无显著意义(P>0.05), 实验组与对照组生存率比较差异有显著意义(P<0.05)。结论　无水乙醇顺行性淋巴结封闭对肺癌转移有较大的影响, 能够达到比较理想的淋巴结清扫目的。     

Intracerebroventricular injection of antisense oligos to nNOS decreases rat ethanol intake

Nitric oxide (NO) has been implicated in alcohol drinking behavior using NO synthase (NOS) inhibitors that are nonselective of the different isoforms of NOS. In the brain, there are two constitutive isoforms of NOS, neuronal NOS (nNOS) and endothelial NOS (eNOS). We used an antisense oligodeoxynucleotide directed against nNOS in ethanol dependent male Wistar rats to examine the specific contribution of nNOS in the control of ethanol intake. Rats were subjected to a free-choice situation water/ethanol (10% v/v) after chronic ethanol intoxication by inhalation of ethanol vapor. During the free-choice situation, rats were twice daily for 4 days intracerebroventricularly injected with either saline, or end-capped phosphorothioate-protected antisense or mismatch oligodeoxynucleotide (25 microg/4 microl per injection), or acamprosate (1 mg/kg body weight) as reference product for its anticraving properties. Our results showed that the antisense treatment, but not the mismatch treatment, reduced both ethanol intake and ethanol preference during treatment and posttreatment periods (by 25-30%) without alteration of the body weight gain. The antisense treatment, but not the mismatch treatment, also down-regulated nNOS mRNA levels (by 30%) and NOS activity in the hippocampus. The anticraving drug, acamprosate reduced both ethanol intake (by 58%) and ethanol preference. All these results suggest that nNOS is involved in the regulation of alcohol dependence.     

肝动脉栓塞化疗术联合经皮无水乙醇注射治疗少血供肝癌的疗效观察

目的评价选择性肝动脉栓塞化疗术（TACE）联合经皮无水乙醇注射（PEI）治疗少血供肝癌的临床效果。方法收集经肝穿刺活检、螺旋CT增强及数字减影血管造影机检查为少血供肝癌患者40例的临床资料进行回顾性分析。20例仅行TACE治疗为TACE组,20例行TACE联合PEI治疗为TACE＋PEI组,比较2组患者治疗有效率、甲胎蛋白转阴率及术后1、2年生存率。结果TACE＋PEI组和TACE组治疗有效率分别为85％（17／20）和55％（11／20）,甲胎蛋白转阴率分别为85％（17／20）和50％（10／20）,术后1年生存率分别为95％（19／20）和75％（17／20）,术后2年生存率分别为70％（14／20）和35％（7／20）。2组患者治疗有效率、甲胎蛋白转阴率及术后2年生存率比较,差异均有统计学意义（均P〈0．05）。结论TACE联合PEI治疗少血供肝癌安全有效。