表面活性剂对HPMA和ATMP缓蚀阻垢性能的影响

表面活性剂的加入明显地提高水解聚马来酸酐(H PMA)和氨基三甲叉膦酸(ATMP)的阻垢性能,阻垢性能随Ca2+浓度的增加而提高,在pH 值6～9时药剂的阻垢性能稳定.     

Strategies to Overcome the Barrier of Ischemic Microenvironment in Cell Therapy of Cardiovascular Disease

The transplantation of various immune cell types are promising approaches for the treatment of ischemic cardiovascular disease including myocardial infarction (MI) and peripheral arterial disease (PAD). Major limitation of these so-called Advanced Therapy Medicinal Products (ATMPs) is the ischemic microenvironment affecting cell homeostasis and limiting the demanded effect of the transplanted cell products. Accordingly, different clinical and experimental strategies have been evolved to overcome these obstacles. Here, we give a short review of the different experimental and clinical strategies to solve these issues due to ischemic cardiovascular disease.     

The Solubility of the Oil Scale Inhibitor Amino Trimethylene Phosphonic Acid in Different Binary Solvents

Amino trimethylene phosphonic acid (ATMP) is a common scale inhibitor using in oil field that always combines with a variety of surfactants and auxiliaries. It is necessary to know its solubility for purifying and combining. With a laser monitoring observation technique, the solubility of amino ATMP in binary solvent mixtures were measured by using the isothermal method from 298.15 to 343.15 K. Results of these measurements were correlated by the combined nearly ideal binary solvent (CNIBS)/Redlich-Kister equation. For these data studied, the CNIBS/Redlich-Kister equation was found to provide an accurate mathematical representation of the experimental data.     

Improving Human Induced Pluripotent Stem Cell-Derived Megakaryocyte Differentiation and Platelet Production

Several protocols exist for generating megakaryocytes (MKs) and platelets from human induced pluripotent stem cells (hiPSCs) with limited efficiency. We observed previously that mesoderm induction improved endothelial and stromal differentiation. We, therefore, hypothesized that a protocol modification prior to hemogenic endothelial cell (HEC) differentiation will improve MK progenitor (MKP) production and increase platelet output. We further asked if basic media composition affects MK maturation. In an iterative process, we first compared two HEC induction protocols. We found significantly more HECs using the modified protocol including activin A and CHIR99021, resulting in significantly increased MKs. MKs released comparable platelet amounts irrespective of media conditions. In a final validation phase, we obtained five-fold more platelets per hiPSC with the modified protocol (235 ± 84) compared to standard conditions (51 ± 15; p < 0.0001). The regenerative potency of hiPSC-derived platelets was compared to adult donor-derived platelets by profiling angiogenesis-related protein expression. Nineteen of 24 angiogenesis-related proteins were expressed equally, lower or higher in hiPSC-derived compared to adult platelets. The hiPSC-platelet’s coagulation hyporeactivity compared to adult platelets was confirmed by thromboelastometry. Further stepwise improvement of hiPSC-platelet production will, thus, permit better identification of platelet-mediated regenerative mechanisms and facilitate manufacture of sufficient amounts of functional platelets for clinical application.     

用半微分阳极溶出伏安法测定锌－ATMP锌－半胱氨酸配合物组成及条件生成常数

应用类似于配位剂滴定锌的安培滴定法来测定Ｚｎ－ＡＴＭＰ、Ｚｎ－ＣｙＳ配合物的组成及条件生成常数，其滴定曲线是用半微分阳极溶出伏安法检测未反应的锌而获得，所得结果满意。     

Upgrading Monocytes Therapy for Critical Limb Ischemia Patient Treatment: Pre-Clinical and GMP-Validation Aspects

Advanced cell therapy medicinal products (ATMP) are at the forefront of a new range of biopharmaceuticals. The use of ATMP has evolved and increased in the last decades, representing a new approach to treating diseases that are not effectively managed with conventional treatments. The standard worldwide recognized for drug production is the Good Manufacturing Practices (GMP), widely used in the pharma production of synthesized drugs but applying also to ATMP. GMP guidelines are worldwide recognized standards to manufacture medicinal products to guarantee high quality, safety, and efficacy. In this report, we describe the pre-clinical and the GMP upgrade of peripheral blood mononuclear cell (PBMC) preparation, starting from peripheral blood and ending up with a GMP-grade clinical product ready to be used in patients with critical limb ischemia (CLI). We also evaluated production in hypoxic conditions to increase PBMC functional activity and angiogenic potential. Furthermore, we extensively analyzed the storage and transport conditions of the final product as required by the regulatory body for ATMPs. Altogether, results suggest that the whole manufacturing process can be performed for clinical application. Peripheral blood collected by a physician should be transported at room temperature, and PBMCs should be isolated in a clean room within 8 h of venipuncture. Frozen cells can be stored in nitrogen vapors and thawed for up to 12 months. PBMCs resuspended in 5% human albumin solution should be stored and transported at 4 °C before injection in patients within 24 h to thawing. Hypoxic conditioning of PBMCs should be implemented for clinical application, as it showed a significant enhancement of PBMC functional activity, in particular with increased adhesion, migration, and oxidative stress resistance. We demonstrated the feasibility and the quality of a GMP-enriched suspension of monocytes as an ATMP, tested in a clean room facility for all aspects related to production in respect of all the GMP criteria that allow its use as an ATMP. We think that these results could ease the way to the clinical application of ATMPs.     

Assessment of Automated Flow Cytometry Data Analysis Tools within Cell and Gene Therapy Manufacturing

Flow cytometry is widely used within the manufacturing of cell and gene therapies to measure and characterise cells. Conventional manual data analysis relies heavily on operator judgement, presenting a major source of variation that can adversely impact the quality and predictive potential of therapies given to patients. Computational tools have the capacity to minimise operator variation and bias in flow cytometry data analysis; however, in many cases, confidence in these technologies has yet to be fully established mirrored by aspects of regulatory concern. Here, we employed synthetic flow cytometry datasets containing controlled population characteristics of separation, and normal/skew distributions to investigate the accuracy and reproducibility of six cell population identification tools, each of which implement different unsupervised clustering algorithms: Flock2, flowMeans, FlowSOM, PhenoGraph, SPADE3 and SWIFT (density-based, k-means, self-organising map, k-nearest neighbour, deterministic k-means, and model-based clustering, respectively). We found that outputs from software analysing the same reference synthetic dataset vary considerably and accuracy deteriorates as the cluster separation index falls below zero. Consequently, as clusters begin to merge, the flowMeans and Flock2 software platforms struggle to identify target clusters more than other platforms. Moreover, the presence of skewed cell populations resulted in poor performance from SWIFT, though FlowSOM, PhenoGraph and SPADE3 were relatively unaffected in comparison. These findings illustrate how novel flow cytometry synthetic datasets can be utilised to validate a range of automated cell identification methods, leading to enhanced confidence in the data quality of automated cell characterisations and enumerations.     

水处理剂ATMP测试方法探讨

现行测试ATMP活性组分方法有HG/T2841-1997（97版）和HG/T2841-2005（05本文结果05版标准操作简单,终点易判定,测试结果的精密度≥0.2%,规定了ATMP含量测试方法,有利于得到准确的检验结果。     

PASP和ATMP复合阻垢剂阻垢性能研究

采用静态阻垢法对聚天冬氨酸(PASP)与氨基三亚甲基膦酸(ATMP)复配物阻垢性能进行研究。考察阻垢剂添加量、温度、Ca2+浓度、HCO3-浓度、恒温时间对阻垢率的影响。结果表明,复配物的阻垢性能较单一的聚天冬氨酸有一定的提高。复配物的最佳质量配比为1∶1,PASP和ATMP总加入量为4 mg/L时效果最佳,阻垢率达86%。复配物阻垢性能受温度、时间、HCO3-浓度的影响较小,受Ca2+浓度的影响较大。对复合阻垢剂进行了经济性评价,复合阻垢剂可降低单独使用时的成本。     

绿色环保阻垢剂聚天冬氨酸的合成及性质研究

以马来酸酐和尿素为合成聚天冬氨酸(PASP),考察了磷酸和三氯化铝两种催化剂的催化作用,同时利用静态阻垢法评价了PASP的FRIA性能,测定了PASP与氨基三甲叉膦酸(ATMP)复配物的阻垢性能,结果表明:在原料比为1:0.5,170℃下反应3h,产率为91.09%,阻垢率为81.17%,PASP与ATMPI:1复配,...