派罗宁B褪色光度法测微量肝素

在pH 4.10的Britton-Robinson缓冲溶液中,肝素与派罗宁B形成离子缔合物,染料发生明显的褪色,体系吸光度的降低与肝素钠浓度成正比,肝素浓度在0～50 μg·(25 mL)-1范围内符合比耳定律.研究了表面活性剂和共存物质的影响,表明方法选择性好.用于肝素钠注射液效价的测定,结果令人满意.     

Affinity and Specificity for Binding to Glycosaminoglycans Can Be Tuned by Adapting Peptide Length and Sequence

Although glycosaminoglycan (GAG)–protein interactions are important in many physiological and pathological processes, the structural requirements for binding are poorly defined. Starting with GAG-binding peptide CXCL9(74-103), peptides were designed to elucidate the contribution to the GAG-binding affinity of different: (1) GAG-binding motifs (i.e., BBXB and BBBXXB); (2) amino acids in GAG-binding motifs and linker sequences; and (3) numbers of GAG-binding motifs. The affinity of eight chemically synthesized peptides for various GAGs was determined by isothermal fluorescence titration (IFT). Moreover, the binding of peptides to cellular GAGs on Chinese hamster ovary (CHO) cells was assessed using flow cytometry with and without soluble GAGs. The repetition of GAG-binding motifs in the peptides contributed to a higher affinity for heparan sulfate (HS) in the IFT measurements. Furthermore, the presence of Gln residues in both GAG-binding motifs and linker sequences increased the affinity of trimer peptides for low-molecular-weight heparin (LMWH), partially desulfated (ds)LMWH and HS, but not for hyaluronic acid. In addition, the peptides bound to cellular GAGs with differential affinity, and the addition of soluble HS or heparin reduced the binding of CXCL9(74-103) to cellular GAGs. These results indicate that the affinity and specificity of peptides for GAGs can be tuned by adapting their amino acid sequence and their number of GAG-binding motifs.     

Controlled heparinase‐catalyzed degradation of polyelectrolyte multilayer capsules with heparin as responsive layer

This work describes the enzymatic degradation of combined hollow capsules via layer‐by‐layer (LbL) self‐assembly technique. They previously showed the build‐up and characterization of capsules composed of synthetic [Poly(sodium 4‐styrene‐sulfonate)/Poly(allylamine hydrochloride)] and biodegradable (Heparin/Chitosan) polyelectrolytes. Biocatalytic response of assembled multilayer capsules provides a more functional and oriented approach in controlled release of encapsulated molecules: in this case multilayer capsule was disassembled by heparinase. Morphological change of individual capsule was assessed with Atomic Force Microscopy and Confocal Laser Scanning Microscopy. The sustained release of encapsulated FITC‐Dextran model was realized under enzymatic degradation of the capsule shells by heparinase. The release profile of FITC‐Dextran indicated the successful control in a concentration‐dependent manner, which shows the applicability as smart drug delivery system. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44916.     

医用金属表面溶胶-凝胶法和离子束合成TiO2薄膜的结构、性能比较

采用溶胶－凝胶法和离子束增强沉积法在医用NiTi合金表面制备TiO2薄膜以提高其生物相容性。利用X射线衍射（XRD）、原子力显微镜（AFM）和X光电子能谱（XPS）对薄膜的结构、表面形貌及组成进行了比较研究；电化学腐蚀实验表明，两种方法制备的TiO2薄膜对金属基体均起到一种保护膜的作用，能够提高医用金属材料在模拟体液中的抗腐蚀性；对薄膜表面固定肝素抗凝血分子进行研究发现，溶胶－凝胶法制备的TiO2薄膜表面能够获得较好的肝素固定效果。     

Microwave-assisted immobilization of heparin onto polyurethane surface for improving blood compatibility

Heparin was covalently immobilized onto polyurethane surface via a PEG spacer by a microwave-assisted approach to improve blood compatibility. Firstly, amino-terminated poly（ethylene glycol） （APEG） was rapidly grafted onto PU surface within 20 rain by a two-step method involving microwave-assisted MDI-functionalization and subsequent microwave-assisted APEG coupling. Then, heparin was eovalently immobilized through an amide linkage by the direct coupling of the carboxylic acid of heparin with the amino group of APEG on PU surface using carbodiimide coupling reaction. The surface structure and properties were characterized by X-ray photoelectron spectroscopy （XPS）, atomic force microscopy （AFM） and water contact angle measurements. The results revealed that hepadn-immobilized PU surface had slightly increased roughness and significantly improved hydrophilicity in comparison to the original PU surface. The anticoagulant activity of films was evaluated by whole blood clotting time （CT） and prothrombin time （PT）. Complement activation was assessed by detecting complement fragment 3a concentrations of serum exposed to the films. The results revealed that the microwave-assisted heparin-immobilized PU films had excellent antithrombogenicity and suppressed complement activation, indicating improved blood compatibility.     

用分子对接方法研究肝素与孕激素受体相互结合模式(英文)

用分子对接模拟软件研究了肝素与孕激素受体的相互作用。以肝素中的一糖单位作为探针对孕激素受体蛋白进行搜索,获得肝素组成单位与孕激素受体的特异性结合模式。结果发现,2-O-硫酸-α-L 艾杜糖醛酸(2-O-sulfated iduronic acid,IdoA(2S))作为肝素的核心组成单糖之一,与孕激素受体的结合能力最好。分子对接结果显示 IdoA(2S)深入到孕激素受体的 helix2 和 helix 11 所包围的结合口袋,与孕激素受体结合结构域关键残基 Asn 719 形成稳固的氢键;并与孕激素受体结合结构域的关键残基 Met 909 残基侧链近距离接触,揭示了 IdoA(2S)可能具有的孕激素受体拮抗效应的分子作用机制。本模拟实验所建立的模型能够部分解释肝素抑制孕激素依赖性乳腺癌的现象,同时推测了其相应机理。     

中国生化原料药的现状和展望

我国生化制药企业有289家,产品品种达700余种(包括原料药和制剂),工业总产值110亿元,出口交货值超过1亿美元。我国能够生产氨基酸类、多肽与蛋白质类、多糖类、酶类、脂类、核酸及其衍生物类等生化原料药,主要出口产品包括肝素、玻璃酸、硫酸软骨素、甲壳质、尿激酶、胰酶、辅酶A和胱氨酸等。中国用于生产生化原料药的生物原料极为丰富,且许多生化原料药在今后相当长时间内还属于资源依赖性产品,我国发展生化原料药应以生物提取和纯化为主要生产方法,同时发展微生物发酵工程和基因重组等现代生物技术。     

Safety studies on intravenous infusion of a potent angiogenesis inhibitor: taurocholate-conjugated low molecular weight heparin derivative LHT7 in preclinical models

Context: As a class of angiogenesis inhibitors, heparin conjugates have shown significant effectiveness in several studies.

Objectives: The purpose of our current study is to evaluate the effectiveness and safety of infusing the conjugate of low molecular weight heparin and taurocholate (LHT7), which has been developed as a potent angiogenesis inhibitor.

Methods: To evaluate its safety, the method of intravenous infusion was compared with its i.v. bolus administration. Intravenous infusion was administered at a rate of 400?μl/min/kg of body weight for 30?min. Pharmacokinetic (PK) analysis, organ accumulation, and plasma concentration profiles of LHT7 were measured. The anticancer effect of LHT7 was evaluated in murine and human xenograft models, and preclinical studies were performed in SD rats and beagle dogs.

Results: The results of the PK studies showed reduced organ accumulation in mice and the AUC_(0–96?h) (area under the curve) was increased up to 1485?±?125?h?×?μg/ml. The efficacy, at dose 1?mg/kg/2 d was higher for i.v. infusion than for i.v. bolus administration in both murine and human cancer models. The preclinical studies showed the safety dose of LHT7 is less than 20?mg/kg in SD rats and in the next safety analysis in beagle dogs showed that there were no organ-specific adverse effects in higher doses, such as, 12?mg/kg. LHT7 showed sustained effects with minimized adverse events when administered through i.v. infusion.

Conclusions: LHT7 (i.v. infusion) could be safely used for further clinical development as a multi-targeting anti-angiogenic agent.     

Surface Modification of Silicone with Covalently Immobilized and Crosslinked Agarose for Potential Application in the Inhibition of Infection and Omental Wrapping

In peritoneal dialysis (PD), the catheter, usually made of silicone, has been considered the “lifeline” of the patient. However, the PD catheter also serves as a nidus for bacterial infection. Furthermore, complications can result from fibrin deposition and omental wrapping of the catheter, which obstructs the dialysate flow. In this work, a crosslinked agarose (AG) polymer layer is covalently grafted as a microscale coating on the silicone surface. This coating reduces Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa biofilm formation by more than two orders of magnitude. In addition, cell and platelet adhesion and protein adsorption is also reduced by ≥90%. Without compromising the antibacterial and antifouling property, further improvement in hemocompatibility, as shown by the inhibition of platelet adhesion and activation, prolonged plasma recalcification time and lower hemolysis degree, is achieved by co‐immobilization of 2.6 μg cm^?2 of heparin (HEP) in the agarose coating. The AG–HEP coatings are not cytotoxic to mammalian cells, and are stable for extended periods in lysozyme aqueous solution and under autoclaving at 121 °C for 20 min.     

肝素钠乳膏治疗干性湿疹和神经性皮炎临床疗效观察

目的观察肝素钠乳膏(海普林)治疗干性湿疹和神经性皮炎的临床效果。方法采用肝素钠乳膏外涂治疗干性湿疹和神经性皮炎共120例。结果应用肝素钠乳膏治疗干性湿疹和神经性皮炎,有效率分别达到80%和87%。结论肝素钠乳膏治疗干性湿疹和神经性皮炎的疗效满意。