Dose and Load Studies for Subcutaneous and Oral Delivery of Poly(lactide-co-glycolide) Microspheres Containing Ovalbumin

Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 µm were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 µg of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fishers paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 µg OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freunds adjuvant.     

Polymeric Microspheres Prepared by Spraying into Compressed Carbon Dioxide

Purpose. The objective was to prepare polymeric microparticles by atomizing organic polymer solutions into a spray chamber containing compressed CO₂ (PCA-process) and to study the influence of various process parameters on their morphological characteristics. Methods. The swelling of various pharmaceutically acceptable polymers [ethyl cellulose, poly(methyl methacrylate), poly(-caprolactone), poly(dl-lactide), poly(l-lactide) and poly(dl-lactide-glycolide) copolymers] in CO₂ was investigated in order to find polymers which did not agglomerate during the spraying process. Poly(l-lactide) (L-PLA) microparticles were prepared by spraying the organic polymer solution into CO₂ in a specially designed spraying apparatus. The effect of various process (pressure and temperature of the CO₂ phase, flow rate) and formulation (polymer concentration) variables on the morphology and particle size of L-PLA-microparticles was investigated. Results. Polymers with low glass transition temperatures agglomerated even at low temperatures. The formation of microparticles was favored at moderate temperatures, low polymer concentrations, high pressures and high flow rates of CO₂. High polymer concentrations and low flow rates resulted in the formation of polymeric fibers. Colloidal L-PLA particles could also be prepared with this technique in a surfactant-free environment. Initial studies on the microencapsulation of drugs resulted in low encapsulation efficiencies. Conclusions. The PCA method is a promising technique for the preparation of drug-containing microparticles. Potential advantages of this method include the flexibility of preparing microparticles of different size and morphology, the elimination of surfactants, the minimization of residual organic solvents, low to moderate processing temperatures and the potential for scale-up.     

5%声振人血白蛋白空气微球蛋白含量测定

采用高效液相凝胶色谱法（ＧＣ－ＨＰＬＣ）、醋酸纤维膜电泳和半微量定氮法测定５０％声振人血白蛋白空气微球制剂中球壁蛋白的含量。ＧＣ－ＨＰＬＣ确证了球壁蛋白主要成分为人血白蛋白;醋酸纤维膜电泳测定空气人血白蛋白微球制剂中人血白蛋白纯度＞９０％;半微量定氮法测出球壁蛋白含量平均值为３．５６％左右,９９％正常值范围为２．５２％－４．６０％。     

湿法纺制PEI／PES中空纤维气体分离共混膜

采用湿法纺丝工艺纺制了聚醚酰亚胺（ＰＥＩ）－聚苯醚砜（ＰＥＳ）中空纤维Ｈ２－Ｎ２和Ｈｅ－Ｎ２分离共混膜,得到Ｈ２和Ｈｅ的渗透通量及选择性为：ＪＨ２＝３６０ＧＰＵ,αＨ２／Ｎ２＝１６２,ＪＨｅ＝１８１ＧＰＵ,αＨｅ／Ｎ２＝７６．７;研究了芯液组成及其流量对膜性能的影响。通过扫描电镜,分析了中空纤维膜的结构,讨论了膜制备过程中的相转化原理。     

应力场下固—液相分离制备微孔聚丙烯中空纤维膜

将聚丙烯和石蜡油的混合物熔融挤出,使之在较高的应力场下冷却和相分离,得到了弹性聚丙烯中空纤维。这种部分结晶的弹性纤维可能具有平行排列的片晶结构,石蜡油存在于片晶之间。将石蜡油提取掉后稍加拉伸即可得到透气性很好的微孔中空纤维渗透膜。     

白及微球的研制及其肝动脉栓塞实验研究

用乳化－冷凝技术首次制备出白及微球,并通过正交实验,确定了制备特定粒径微球的最佳工艺条件。对微球的外观、粒径与分布、溶胀度及血液相容性等进行了研究。微球平均粒径为５４．３６μｍ,粒径范围５０～９０μｍ,占总数的７８．３７％;微球在ｐＨ＝７．４的缓冲液中有一定的溶胀性;血液相溶性良好。实验小猪微球栓塞后的肝动脉造影表明白及微球可致肝右动脉一级、二级分支完全栓塞;病理检查表明梗死区可见肝组织呈肝硬化改变,大量的假小叶形成。微球栓塞后,ＧＰＴ有一过性升高,３周后恢复正常。实验结果表明,以白及胶为材料制备的微球将为癌症的治疗提供一种新型的栓塞治疗剂     

异丙酚复合芬太尼维持麻醉对脑代谢的影响

观察异丙酚复合芬太尼维持麻醉对脑代谢的影响。方法： 择期手术病人８ 例, 芬太尼、硫贲妥钠、维库溴铵诱导插管, 静脉联接Ｇｒａｓｅｂｙ 微泵异丙酚８ ｍｇ／ （ｋｇ·ｈ） , 芬太尼１ μｇ／ （ｋｇ·ｈ）维持麻醉。连续监测ＭＡＰ、心电图、脉搏氧饱和度和呼气末二氧化碳分压, 同步采集动脉血和颈内静脉血作血气分析, 计算动－ 静脉氧含量差（Ｄａ － ｖＯ２） 和脑氧摄取率（ＥＲＯ２） 。结果： 异丙酚麻醉维持平稳, Ｄａ － ｖＯ２ 和ＥＲＯ２ 在给药３０ ｍｉｎ 、６０ ｍｉｎ 较气管插管后５ ｍｉｎ 无明显改变, 有平均动脉压下降和心动过缓。结论： 异丙酚复合芬太尼维持麻醉可保持脑氧供需平衡稳定。     

隔核内注射吗啡对海马痛单位的影响

目的：探讨隔核内阿片主相应的受体在隔核影响海马单位中的作用。方法：参照Ｓａｗｙｅｒ兔脑图谱,用ＳＮ－２型推进器以２μｍ／ｓ速度将玻璃微电极插入海马Ｐ２．５,Ｌ３－６,Ｈ６－９处引导神经元自发放电;在Ａ３Ｒ１Ｈ２（外侧隔核）处插入钨比有,人和刺激隔核用;在Ａ２Ｒ１Ｈ２及中脑导水管周围灰质（ＰＡＧ）Ｐ９．５Ｒ１Ｈ１．５）处分别埋不锈钢微量注射套管,用牙托水配牙托粉固定,作脑室注射用。结果：共引导８５个     

Efficiency of Superfine Glass Fiber Membrane\= Filters for Depleting Leukocytes

ＩｎｔｒｏｄｕｃｔｉｏｎＩｎｔｈｅｄｏｎｏｒｂｌｏｏｄｃｏｌｅｃｔｅｄｂｙｂｌｏｏｄｃｅｎ－ｔｅｒｓ,ｌｅｕｋｏｃｙｔｅｓｈａｖｅｎｏｔｈｅｒａｐｅｕｔｉｃｆｕｎｃｔｉｏｎｔｏｐａｔｉｅｎｔｓｂｕｔｍａｙｉｎｄｕｃｅｍａｎｙｓｉｄｅｅｆｅｃｔｓ．Ｃｏ...     

Effects of dihydroergotamine (DHE) on blood flow and metabolism in the underperfused myocardium in anaesthetized dogs

Summary The study was carried out in 13 mongrel dogs. Regional myocardial blood flow was measured using radiolabelled microspheres. Lactate, H⁺-ions, and O₂ content were measured in arterial and local venous blood. Partial occlusion of the ramus circumflexus (LCX) led to a decrease in left ventricular dp/dt max, systemic arterial pressure, and a marked release of lactate from the underperfused myocardium. With DHE (2 g/kg infused within 5 min, 8 dogs), a slight decrease in heart rate, left ventricular dp/dt max, LCX-resistance and a small increase in femoral and total peripheral resistance as well as in arterial and left and right atrial pressure was observed. In the normally perfused and in the underperfused part of the left ventricle microsphere assessed blood flow was unchanged or slightly elevated with DHE. Lactate release from the underperfused myocardium was markedly reduced. None of the DHE-induced effects on hemodynamic and metabolic parameters were observed in control experiments with infusion of 0.9% NaCl (5 ml). The results indicate that DHE leads to an amelioration of impaired metabolism in the underperfused myocardium and exerts no vasoconstriction in this area.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung.