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L-^(10)BPA中间体合成工艺优化及连续流可行性工艺研究
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作者 关东 董珍 +4 位作者 陈凯 李国威 廖竞远 黄均荣 游恒志 《当代化工研究》 CAS 2023年第21期143-145,共3页
利用硼-10酸作为原料与正丁醇反应后,再与格氏试剂异丙基氯化镁制备(S)-Boc-4-二羟基硼10基-苯丙氨酸。通过设计正交实验优化了该反应的釜式反应条件和后处理方式,釜式克级反应分离收率可达63%。在最优的釜式反应条件基础上进行连续流反... 利用硼-10酸作为原料与正丁醇反应后,再与格氏试剂异丙基氯化镁制备(S)-Boc-4-二羟基硼10基-苯丙氨酸。通过设计正交实验优化了该反应的釜式反应条件和后处理方式,釜式克级反应分离收率可达63%。在最优的釜式反应条件基础上进行连续流反应,制备含10B的L-10BPA中间体,反应时间由釜式反应的17h缩短至2h,分离收率达到了57%,验证了含10B的L-10BPA中间体连续流反应的可行性,且连续流工艺具有反应速度快、安全性好等优点,适合工业放大生产。 展开更多
关键词 L-10bpa 连续流 工艺研究
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<i>In Vitro</i>Evaluation System of Pharmacokinetics and Irradiation Effect in Boron Neutron Capture Therapy (BNCT) Using Three-Dimensional Artificial Human Tumor Tissue Model 被引量:1
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作者 Shintaro Ishiyama Yoshiya Asano +2 位作者 Minoru Suzuki Mitsuru Akashi Hiroshi Shimoda 《Journal of Cancer Therapy》 2019年第10期835-845,共11页
Boron neutron capture therapy (BNCT) is based on the incorporation of boron-containing drugs to cancer cells and the nuclear reaction of 10B atoms by thermal neutron irradiation results in tumor degeneration. For the ... Boron neutron capture therapy (BNCT) is based on the incorporation of boron-containing drugs to cancer cells and the nuclear reaction of 10B atoms by thermal neutron irradiation results in tumor degeneration. For the development of this therapy, currently, long time and high cost consuming experiments using many animals are required. In this study, we constructed a new in vitro evaluation system for BNCT by combination of an artificial tumor tissue model, comprised of normal human dermal-derived fibroblast (NHDF) and human pancreatic cancer cell line BxPC3, and the optical plastic material CR-39 as a solid state nuclear track detector. Administration of boronophenylalanine (10BPA) as a boron-containing drug and neutron irradiation up to 2.52 × 1012 n/cm2 to the control tissue constructed by NHDF (NHDF3D) and BxPC3 cell loaded tissue (NHDF3D/BxPC3) resulted in detection of 1.6 times higher number of α-ray/recoiled Li particle tracks in NHDF3D/BxPC3 in comparison to NHDF3D, demonstrating that putative irradiation damage to cancer cells can be evaluated by this system. On a cellular level, the hit number of α-ray/recoiled Li particle tracks per single BxPC3 cells and NHDF was evaluated as 5.46 and 1.71, respectively. The tumor and normal tissue ratio (T/N ratio) was 3.19, which was corresponded with those of BPA as 2 - 4 that reported in the previous studies. This new in vitro evaluation system may provide a useful tool for a low cost, labor-saving, and non-animal method for the development of new boron-containing drugs or improvement of BNCT conditions. 展开更多
关键词 Boron Neutron Capture Therapy (BNCT) boronophenylalanine (10bpa) Artificial Human Tumor TISSUE MODEL Cell Accumulation Method
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Radiation Sensitivity of <i>in Vitro</i>Evaluation System of Pharmacokinetics in Boron Neutron Capture Therapy (BNCT) Using Three-Dimensional Artificial Human Tumor Tissue Model
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作者 Shintaro Ishiyama Minoru Suzuki 《Journal of Cancer Therapy》 2019年第12期1025-1035,共11页
One of the important matters that must be determined in advance when performing BNCT treatment is the optimization of neutron irradiation time and dose. In this article, following the previous article (2.52 × 101... One of the important matters that must be determined in advance when performing BNCT treatment is the optimization of neutron irradiation time and dose. In this article, following the previous article (2.52 × 1012 n/cm2) (Case 1), double irradiation (5.04 × 1012 n/cm2) was further performed (Case 2) by verifying the radiation sensitivity performance of the artificial tumor tissue NHDF3D/BxPC3 and the possibility of evaluating the optimum neutron dose required for treatment was examined. As a result, although the radiation damage rate in the normal tissue NHDF3D and the tumor tissue BxPC3 increased in proportion to the irradiation dose due to heavy irradiation in Case 1 or more, the increase in the damage rate in the normal tissue exceeded the tumor tissue. Furthermore, the tumor/normal tissue damage ratio T/N ratio showed the maximum value in Case 1, and the dose ratio in Case 2 with a higher dose showed a tendency to decrease. From the above experimental facts, it was shown that irradiation dose optimization is possible to some extent by an evaluation method using an artificial tumor tissue. 展开更多
关键词 Boron Neutron Capture Therapy (BNCT) boronophenylalanine (10bpa) Artificial Human Tumor TISSUE MODEL Cell Accumulation Method
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对二羟基苯丙氨酸硼-硼中子俘获治疗临床应用进展
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作者 韩青青 杨乔 +1 位作者 李拓 霍力 《中国医学装备》 2024年第9期162-167,共6页
硼中子俘获治疗(BNCT)是一种基于核俘获和核裂变反应的放射治疗模式。对二羟基苯丙氨酸硼(BPA)是BNCT中应用最广泛的肿瘤细胞选择性载硼药物。当前,国内外开展多项BPA-BNCT治疗脑肿瘤、黑色素瘤及头颈部肿瘤等多种肿瘤的临床试验,其有... 硼中子俘获治疗(BNCT)是一种基于核俘获和核裂变反应的放射治疗模式。对二羟基苯丙氨酸硼(BPA)是BNCT中应用最广泛的肿瘤细胞选择性载硼药物。当前,国内外开展多项BPA-BNCT治疗脑肿瘤、黑色素瘤及头颈部肿瘤等多种肿瘤的临床试验,其有效性已得到一定程度的证实。为提高BPA-BNCT疗效,多项研究探索了BPA联合其他载硼药物、BPA-BNCT联合化疗药物或BPA-BNCT联合放射治疗的多种治疗模式,但上述治疗模式对肿瘤患者的预后改善能力仍存疑。目前BPA-BNCT发展受到载硼药物及中子设备等方面的限制,但随着第三代载硼药物的开发及加速器BNCT(ABBNCT)的建设成功,BNCT的应用前景十分广阔。综述BPA-BNCT在多种恶性肿瘤的临床研究的新进展,探讨BNCT临床研究面临的机遇与挑战。 展开更多
关键词 硼中子俘获治疗(BNCT) 对二羟基苯丙氨酸硼(BPA) 脑肿瘤 黑色素瘤
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