Effects of a Diluent on the Retarded–Release Property of Acrylate Methacrylate–Salicylic Acid Coacervates

Pharmaceutical Research -     

Serum galactosylhydroxylysyl glucosyltransferase in acute myocardial infarction and during subsequent collagen scar formation

Changes in serum galactosylhydroxylysyl glucosyltransferase, an enzyme catalysing one of the intracellular post-translational modifications in collagen biosynthesis, were studied in twenty-four patients with acute myocardial infarction. The enzyme activity was monitored for 18 days from the onset of infarction, and at least a two-peaked pattern was observed. The first peak corresponded to the stage of acute myocardial injury, there being a highly significant correlation between the maximal values for serum glucosyltransferase and alpha-hydroxybutyrate dehydrogenase. An average decreasing in serum glucosyltransferase activity of 41%, was noted during the following 24 h. A new gradual rise in serum glucosyltransferase activity, interpreted as indicating myocardial collagen scar formation, was observed 5 days after the onset of infarction, when the serum enzyme activities indicating myocardial injury had already declined. The average daily values for serum glucosyltransferase between 6 and 18 days correlated highly significantly with the maximal value for serum alpha-hydroxybutyrate dehydrogenase, which serves as a relative estimate of the size of the original myocardial infarction area. The data further suggest that certain other factors including heart failure and/or various drug treatments may also affect the magnitude of this second peak.     

Two-compartment model for plasma pharmacokinetics in individual blood vessels

Plasma pharmacokinetics of sodium fluorescein, fluorescein isothiocyanate conjugated bovine serum albumin, and a graded series of dextrans of 19,400 to 71,800 MW were monitored continuously using a noninvasive photometric technique in individual blood vessels of tissue grown in a rabbit ear chamber. The data obtained were fitted with a two-compartment open model to obtain an effective permeability and an effective clearance. Both parameters decreased with increasing molecular radius for dextrans. Values for albumin were considerably less than expected on the basis of molecular radius, presumably due to the configuration, charge, and binding characteristics of albumin.Supported by grants from the National Science Foundation, the R. K. Mellon Foundation, and the American Cancer Society. In addition, R. K. Jain is a recipient of a Research Career Development Award from the National Institutes of Health, and a Guggenheim Fellowship.     

Effects of tranexamic acid and local fibrin deposition on fibrinolysis and granulation tissue formation in preformed cavities

The effects of locally deposited fibrin and of tranexamic acid-induced antifibrinolysis on forming granulation tissue were studied in the light of a recently developed method for treatment of postoperative fistulas by occlusion with a fibrin clot. Perforated teflon cylinders, either empty or fibrin-filled, were implanted subcutaneously in rats and extracted after 2 weeks. Fibrin deposition was found to stimulate granulation tissue ingrowth into the cylinders but it did not change the fibrinolytic activity in the granulation tissue. A significantly higher fibrinolytic activity was, however, found in the tissue fluid collected from the space between the granulation tissue and the implanted fibrin clot compared to tissue fluid from cylinders implanted empty. Tranexamic acid significantly reduced the fibrinolytic activity on the granulation tissue and delayed lysis of the implanted fibrin clot. It also reduced granulation tissue ingrowth but it did not abolish the positive effects of the clot on granulation tissue formation.     

The Relation Between Granule Size,Granule Stickiness,and Torque in the High-Shear Granulation Process

No HeadingPurpose. To investigate the background of the observed relationship between measured torque and granule size in high-shear granulation processes.Methods. Torque was measured during the granulation process; the behavior of individual wet granules during compaction was investigated using micromanipulation. Surface properties of wet granules were manipulated by coating them with talc.Results. The torque-granule size relationship could not be explained by the rise in mass of the individual granules; it occurs rather through an increase in stickiness of the granules when the moisture content is increased. Obviously, the increased stickiness that causes the granules to grow also increases the torque. Increased stickiness was shown to be the result of an increased deformability of the granules at higher moisture contents, in combination with a change in surface properties. The elastic-plastic behavior (ratio of elastic to plastic deformation) was found to change at increasing moisture contents.Conclusions. Our results imply that changes in the stickiness of the granular material that may be caused by changes in composition shift the torque-size relationship. This may be of particular importance when, for example, granulation results from placebo batches are used to predict the granule size of drug-containing batches.     

Stabilization and Improved <Emphasis Type="BoldItalic">in Vivo</Emphasis> Performance of Amorphous Etoricoxib using Gelucire 50/13

Purpose Amorphous drugs have gained importance because of their advantageous biopharmaceutical properties; however, their stabilization remains a challenge. The purpose of this work was to stabilize the amorphous form of etoricoxib (ET) by using a low excipient/drug ratio to improve drug dissolution and thus bioavailability. Methods The effect of Gelucire and polyvinylpyrrolidone (PVP) on stabilization and bioavailability of amorphous etoricoxib (AET) was studied. X-ray powder diffractometry, differential scanning calorimetry, and scanning electron microscopy were used to study the physical state of the drug. Dissolution studies were performed for melt granules of AET with Gelucire 50/13 (MG-AET) and solid dispersion with PVP (SDP) to differentiate dissolution performance. A stability study on samples was conducted for 3 months to evaluate the physical state of the drug and its dissolution in the formulation. The in vivo performance of the optimized and stable formulation of ET was evaluated in rat. Results Dissolution of MG-AET was significantly improved as compared to AET and SDP. Both factors, amorphization of drug and melt granulation with lipid, seemed to be important for improving dissolution. Stability data revealed that MG-AET was significantly advantageous for AET stabilization, whereas PVP was not. The amount of Gelucire required for the stabilization of one part of AET was 0.5 part (by weight), whereas even 1.5 part (by weight) of PVP failed to elicit the same result. The superior in vivo performance of MG-AET has been attributed to the altered physiochemical properties of AET and the presence of lipid in the system. Conclusion Gelucire can stabilize AET and improve its biopharmaceutical performance at a low excipient/drug ratio and may provide a better alternative to conventional stabilizers such as PVP.     

人脱嘌呤脱嘧啶核酸内切酶单克隆抗体抗原表位的鉴定及应用

目的:研究鉴定人脱嘌呤脱嘧啶核酸内切酶单克隆抗体(hAPE1 mAb)的抗原表位,并建立定量检测hAPE1的ELISA一步法。方法:设计并合成APE1-15肽阵列,鉴定hAPE1 mAb 2-G1和4-F6的抗原表位,应用三维立体结构观察软件Molsoft.ICM-Pro模拟hAPE1 mAb抗原表位的立体结构;采用改良的过碘酸钠法标记抗体,以hAPE1 mAb为捕获抗体和酶标抗体,建立hAPE1的ELISA一步检测法。结果:APE1-15肽阵列检测结果和抗原表位三维结构显示,2-G1mAb的抗原表位对应为hAPE1天然蛋白氨基酸残基序列的76-90位和109-123位,位于氧化还原区域,为构象型抗原表位;4-F6 mAb的抗原表位对应为hAPE1天然蛋白氨基酸序列的109-147位,位于DNA修复内切酶活性区。ELISA一步法检测hAPE1蛋白的线性范围为8.0~200μg/L,最低检测限为2.0μg/L。平均批内变异系数为8.67%,平均批间变异系数为12.45%,平均回收率为105.47%。结论:hAPE1 2-G1 mAb和4-F6 mAb具有不同的抗原表位,成功建立的hAPE1 ELISA一步法为简便、快速、准确检测血清中hAPE1的含量奠定了基础。     

中药药线对口引流法在复杂性肛瘘术后创面愈合观察

目的观察中药药线对口引流法在治疗复杂性肛瘘术后促进创面愈合的临床疗效。方法将60例复杂性肛瘘患者按随机数字表法分为治疗组30例,采用中药药线对口引流法,对照组30例采用切开旷置术,观察术后不同时间点创面愈合率、肉芽生长及治愈率情况。结果与对照组比较,治疗组术后不同时间点肉芽生长明显改善（P〈0．05）,愈合率在第10、14、20天差异有统计学意义（P〈0．05）;治疗组总有效率高于对照组,差异有统计学意义（χ^2=4．043,P〈0．05）。结论中药药线对口引流法治疗复杂性肛瘘,能加快肉芽生长,促进创面愈合,提高临床疗效。     

小儿金丹片制剂工艺研究

目的：研究小儿金丹片制剂生产工艺。方法：以朱砂中HgS的含量为测定指标,采用滴定法测定,比较不同的制剂工艺所得产品中HgS含量。结果：以朱砂中HgS的含量为考察指标,优选出小儿金丹片最佳制剂工艺,即采用高效混合制粒机进行湿法制粒。结论：使用高效混合制粒机对小儿金丹片所用原辅料进行湿法混合制粒,得到HgS含量最为接近投料量。