TACE With Dicycloplatin（TP21） in Patients With Unresectable Hepatocellular Carcinoma: an Open, Parallel-controlled,Multicenter Randomized Phase III Trial

To evaluate the effectiveness and safety of TP21 injection for TACE in treatment of hepatocellular carcinoma:
1. Primary efficacy endpoint: progression-free survival (PFS), which will be assessed by the Independent Review Committee according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST).
2. Secondary efficacy endpoints: PFS, objective response rate (ORR), disease control rate (DCR), overall survival (OS), time to progression (TTP), 1-year progression-free survival, 1-year survival and 2-year survival assessed by the investigator.

开始日期2022-06-09

申办/合作机构

东南大学附属中大医院

100 项与双环铂相关的临床结果

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100 项与双环铂相关的转化医学

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100 项与双环铂相关的专利（医药）

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900

项与双环铂相关的文献（医药）

2025-08-01·Water Research

Nanoplastics pre-exposure to microbial consortium influencing their ability to degrade pollutants: “Stagnation effect” and “Self-recovery”

Article

作者: Song, Tiansong ; Li, Zhicheng ; Yu, Huiying ; Guo, Wenbo ; Cao, Xinde ; Zhao, Ling ; Ma, Xiaoyu ; Qiu, Hao

Nanoplastics (NPs) coexist with microorganisms in global water environmental systems, showing spatial-temporal differentiation. Therefore, studying the behavior of microorganisms previously exposed to NPs is particularly important. With 2,4-dichlorophenol (DCP)-degrading microflora as model microorganisms, this study found that higher dose (10, 100 mg/L) of polystyrene NPs pre-exposure inhibited bacterial DCP degradation prolonging the stagnation period, while lower dose (1 mg/L) of NPs on the contrary stimulated their degradation ability. The degradation delay coefficients (μ) showed a significant positive correlation with the duration of pre-exposure. Specifically, the μ values observed after 1 day, 3 days, and 9 days of pre-exposure to 10 mg/L NPs were 2.5, 2.9, and 3.8, respectively, while those for 100 mg/L NPs were 3.2, 4.0, and 5.1. In contrast, the control group without NPs exhibited a μ value of only 1.9. Pre-exposure caused NPs to enter bacterial cells, leading to oxidative damage, membrane impairment, and potential DNA damage. This carry-over toxicity suppressed the consortium's degradation efficiency of DCP. During the stagnation period, microorganisms were striving to redeem themselves, recovering their abilities of biofilm formation, chemotaxis and motility by upregulating the expression of wspA, mcp, and pilJ gene families, thus reinforcing inter-population regulatory cooperation, thereby restarting the DCP degradation. With the duration of pre-exposure to PS NPs increased, the recovery time required for bacterial communities also lengthened. It is crucial to pay attention to the biological responses to subsequent pollutants triggered by pre-exposure.

2025-06-01·International Journal of Pharmaceutics: X

An iterative process and mixture design approach for dry granulated ternary blends of filler-binders

Article

作者: Märkle, Niclas ; Warnke, Gernot ; Pein-Hackelbusch, Miriam

Roller compaction/dry granulation (RC/DG) is a key process in pharmaceutical manufacturing for improving powder flowability, density, and segregation resistance. Advanced statistical modeling was used to optimize RC/DG process parameters and subsequently binder compositions by employing process and mixture design experiments. The authors used microcrystalline cellulose (MCC), silicified MCC (SMCC), and dicalcium phosphate (DCP) as filler-binder examples in RC/DG experiments. Granule and tablet properties, including flowability, bulk and tapped densities, as well as resistance to crushing, were analyzed using compendial methods. The process design experiments confirmed that RC/DG reduces manufacturability compared to direct compression. Optimal processing conditions, balancing sufficient tablet strengths and granule formation, were identified to be between 20 (SCF * ϑ) [kN/cm] and ∼ 60 (SCF * ϑ) [kN/cm]. Thereby (ϑ) is defined as the screw-to-roll speed ratio and (SFC) as the specific compaction force. Mixture design experiments revealed optimal mixtures balancing SMCC, MCC, and DCP to achieve desired properties like low angle of repose, high bulk density, and strong tablets. These findings provide guidance for selecting formulations and process parameters in RC/DG applications. The derived 'SCF * ϑ'- factor was found to effectively describe the granulation intensity. A superimposed mixture design model based on precise target values of the parameters bulk density, flow properties, and breaking force allowed identification of the best formulation.

2025-05-01·International Journal of Biological Macromolecules

Enhancing mechanical and heat-resistant properties of melt-spun ploy (lactic acid) fiber via crystal structure regulation: The synergistic effects of long-chain branching and drawing process

Article

作者: Zhu, Liping ; Zhu, Meifang ; Guo, Sheng ; Zhou, Zhe ; Zhang, Huanyao ; Zhang, Xiugang ; Yu, Senlong ; Xiang, Hengxue

The fabrication of ploy (lactic acid) (PLA) fiber with adjustable crystal structure and property still remains a great challenge. In this work, a series of melt-spun PLA fibers with increased strength and heat-resistance are prepared via crystal structure, which is caused by the synergistic effects of dicumyl peroxide (DCP) long-chain branching (LCB) modification and drawing process. The chemical structure of LCB-PLA resin is confirmed by the NMR and FTIR spectrum, which indicates that PLA is successfully modified by DCP free radical reaction through reactive extrusion. Moreover, the crystallization behavior and rheological property of PLA resin are significantly influenced by LCB degree. Especially, the PLA-LCB with 0.05 % DCP demonstrates the most ideal crystallinity and thermal stability owing to the micro crosslinking effect of DCP. Finally, the synergistic effects of LCB modification and drawing process on the crystal structure and property of PLA fiber are investigated by WAXD, SAXS, DMA and tensile testing. The tensile strength and glass transition temperature of LCB-PLA-0.05D fiber with 2.4 drawing ratio are increased to 3.25cN/dtex and 76.5 °C, respectively. Therefore, our work presents a feasible approach to fabricate enhanced strength and heat-resistance PLA fiber via crystal structure regulation, which has a bright future of industrialization.

项与双环铂相关的新闻（医药）

2024-11-15

·adalvo.com

Adalvo Secures DCP Approval for Apixaban Tablets

Adalvo announces the successful DCP approval for Apixaban Tablets. Based on the reference brand Eliquis, Apixaban is indicated for the treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). As per IQVIA, total global Apixaban sales for 2023 was $27.7Bn with a 3Y CAGR of 9%. With this approval, Adalvo is well-positioned to bring Apixaban Tablets to market as a crucial treatment option for patients suffering from DVT and PE. The DCP approval of Apixaban Tablets reflects Adalvo's commitment to delivering high-quality, differentiated treatments to our partners. Our rigorous development process ensures that we meet the highest standards of safety and efficacy, providing a reliable alternative for patients in need. There are no half-measures at Adalvo – we are always on target. When your mission is to be faster and stronger than your competitors, you need a winning team driving your vision forward. Partner Up Now!

上市批准

2024-11-15

·adalvo.com

Adalvo Announces Successful EU Approval for Mirabegron 50mg Prolonged-Release Tablets

Adalvo secures successful DCP approval for Mirabegron 50mg prolonged-release tablets. Developed based on the reference brand Betmiga prolonged-release tablets, Mirabegron is indicated for the treatment of urgency, increased micturition frequency, and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. According to IQVIA, Mirabegron achieved approximately $3.3Bn in global sales in 2023, with a 3-year CAGR of 2%. Additionally, registrations for Mirabegron 25mg are currently ongoing, demonstrating Adalvo's commitment to providing a wide range of treatment options. Adalvo’s success in securing this approval reflects our capabilities to develop complex, differentiated products. Building on the success of Mirabegron, Adalvo is also progressing well with the development of Mirabegron+Solifenacin, further expanding our portfolio and enhancing treatment options for patients. There are no half-measures at Adalvo – we are always on target. When your mission is to be faster and stronger than your competitors, you need a winning team driving your vision forward. Partner Up Now! Click Here To Get In Touch! © 2022-2024 Adalvo Limited. All right reserved

上市批准

2024-10-17

·动脉网

深耕20年，1.1类新药TP21已进入3期临床，索普兴大将推出新一代肝癌铂类药物

目前，铂类药物已成为临床中应用最广泛的化疗药物之一，被广泛用于肺癌、膀胱癌、卵巢癌、宫颈癌、食管癌、胃癌、结直肠癌和头颈部肿瘤等常见恶性肿瘤的治疗[1]。然而，前三代铂类药物各自存在着难以克服的局限性，且自第三代铂类药物成功研发并上市后，传统铂类药物的创新进展相对缓慢。 2007年，北京索普兴大医药研究有限公司（以下简称“索普兴大”）加入了铂类药物创新研发的行列。值得一提的是，索普兴大为通盈集团旗下全资子公司，是其医药健康板块研发的主体单位。索普兴大以新一代First-in-Class铂类药物TP21为核心，聚焦抗肿瘤药物的研发、生产与商业化。在其持续推进下，TP21已取得了一系列积极进展。其中，在2022年6月，TP21注射液用于经动脉化疗栓塞术（TACE）治疗肝细胞癌的3期临床试验已全面启动。目前，TP21注射液的3期临床试验正在积极推进中，预计将于2026年递交新药上市申请（NDA）。我国首个具有自主知识产权的1.1类铂类化药，拥有独特“分子开关”设计铂类药物属于细胞周期非特异性药物，在进入肿瘤细胞后，与脱氧核糖核酸（DNA）结合形成Pt-DNA加合物，干扰DNA的复制和转录，从而介导肿瘤细胞坏死或凋亡，最终抑制肿瘤细胞的生长和增殖[1]。尽管不同铂类药物与DNA结合的方式和位点存在一定差异，但其作用机制在广义上是一致的。然而，由于现有常用铂类药物缺乏对肿瘤细胞的特异性，进入人体后，其不仅会与癌症细胞的DNA发生作用，同时也会与正常细胞的DNA发生作用，进而引发一系列毒副作用。常用铂类基本情况图源：公开信息整理，动脉网制图对此，索普兴大开发的铂类药物TP21在分子结构上进行了优化创新，以克服传统铂类药物的局限性与缺点。从分子设计与作用机制来看，TP21是一种通过促进药物与癌细胞核内DNA结合而发挥作用的金属铂类抗肿瘤药。它是基于分子生物学观点，利用癌细胞DNA空间构型的异常特性，设计并制造成功的一种带有“分子开关”的铂类抗肿瘤药物。 TP21的“分子开关”关键位点具有四个氢键结构，使得TP21可以在人体内导向性的与异常DNA的碱基结合，而不与正常的DNA结合。只有当肿瘤细胞DNA复制时解旋酶激活，TP21氢键开关被解旋酶打开后暴露出带有空穴轨道的铂原子（Pt），Pt与带有孤对电子的DNA氮原子结合形成Pt-DNA加合物，将复制癌细胞的机构摧毁，从而介导肿瘤细胞的坏死或凋亡，进而产生抗肿瘤效果、发挥治疗作用[2-4]。因其特有的“分子开关”设计，TP21显示出能够克服传统铂类药物大量破坏正常组织细胞等副作用的潜力，可靶向性杀死肿瘤细胞。作为新一代铂类抗肿瘤药物，TP21所展现出的抗肿瘤效果与未来发展潜力获得了多方的关注与认可。起初，TP21由杨旭清教授领衔开发。TP21先后在国家经贸委、国家科技部立项，并被列为国家863计划、“创新药物和中药现代化”临床研究品种课题、国家“十五”、”十二五“重大科技专项等。此外，核心研发团队先后与北京大学肿瘤医院、中国解放军总医院（301医院）、中国医学科学院肿瘤医院等单位的160多位临床专家建立了合作[3]。目前，TP21已取得多项中国发明专利证书，同时，索普兴大也在积极布局海外专利保护，筑牢坚实的知识产权保护的护城河。临床效果显著，具有高效、低毒、低耐药、广谱抗肿瘤等优势截至目前，TP21已完成了临床前研究、晚期恶性肿瘤1期、晚期非小细胞肺癌2期与原发性肝癌2期临床试验等多项研究。其研究结果表明，TP21具有高效、低毒、广谱抗肿瘤、低耐药、高穿透性等特点，能够更好的识别、杀伤肿瘤细胞，靶向性更强且副作用更低。从临床前研究结果来看，TP21的早期药学及非临床研究数据显示，其对肺癌、前列腺癌等肿瘤具有较好的抑制和杀伤作用，具备单独或联合其他药物治疗、开发新适应症的潜力。例如，在大鼠模型中，通过大鼠静脉分别给予TP21、卡铂、顺铂。与顺铂、卡铂相比，TP21在不同时间分布在血浆、脑、肠、前列腺等不同组织中的浓度均较高。此外，TP21在动物体内试验的结果显示，其抑制肿瘤效率高，并且具有一定的量-效关系[5]。从临床试验研究结果来看。首先，在2000—2001年，韩国MetaBio公司联合美国圣地亚哥癌症研究中心，对TP21开展了一项HDRA体外化疗敏感性实验。结果显示，TP21对多种癌细胞具有杀灭作用且敏感性较高。图源：索普兴大 2005年，TP21注射液1期临床试验正式完成。该项试验在中山大学肿瘤防治中心进行，由我国肿瘤内科学资深学科带头人、著名淋巴瘤专家管忠震教授担任项目负责人。研究结果显示，TP21注射液安全性良好，其胃肠道反应及肾毒性低于顺铂，血液毒性低于卡铂，无明显肾功能损伤。值得注意的是，索普兴大在2008年完成了TP21加紫杉醇和卡铂加紫杉醇的头对头研究。这是一项比较TP21注射液+紫杉醇或卡铂+紫杉醇静脉给药治疗晚期非小细胞肺癌（NSCLC）（IIIB或者IV期）的多中心、随机、对照、开放的2期临床研究[6]。此次试验共纳入了236名符合入选标准的患者，其中TP21组118例、卡铂组118例。受试者随机分配接受双TP21+紫杉醇二联化疗方案或卡铂+紫杉醇二联化疗方案的治疗，每三周给药一次，为一个周期，共治疗4个周期，如果研究者认为继续应用试验药物对患者有可能有益，可以继续治疗至6个周期。研究结果表明，TP21组的患者临床获益和生存获益均高于卡铂组。重要的是，该研究的亚组分析结果显示，TP21组对鳞癌及Ⅳ期肺癌治疗后缓解率及疾病控制率明显优于卡铂组。除此之外，在2020年，索普兴大完成了TP21注射液用于TACE治疗肝细胞癌的有效性和安全性的随机、开放、平行对照、多中心探索性临床试验（2期）[7]。本次试验由中国科学院院士滕皋军教授担任项目负责人，以探索TP21注射液用于TACE治疗肝细胞癌的有效性和安全性。该试验以抗生素类抗肿瘤药盐酸表柔比星为对照，比较TP21注射液或TP21注射液联合盐酸表柔比星用于TACE治疗肝细胞癌的疗效差异。该试验的独立中心评价结果显示，TP21注射液组与TP21注射液联合盐酸表柔比星组在1个月与3个月时的客观缓解率（ORR）均好于盐酸表柔比星组。其临床结果已发表于Europran radiology杂志。据悉，TP21注射液的基础和临床研究数据综合表明，TP21注射液在多种实体肿瘤的治疗中展现出潜力，能够覆盖2/3的实体肿瘤患者，包括肝细胞癌、乳腺癌、肠道肿瘤、泛妇科肿瘤等[8]。目前，TP21注射液用于TACE治疗肝细胞癌的有效性和安全性的随机、开放、平行对照、多中心3期临床试验已全面启动。该项试验由滕皋军教授领衔，在全国43家中心开展。索普兴大负责人曹静婷表示：“目前，TP21注射液的3期临床试验已取得一些初步数据。从单个案例角度看，TP21注射液组的无疾病进展生存期（PFS）数据优于对照组。” 拥有从原料到制剂的一体化生产体系，未来可快速实现产品商业化作为通盈集团医药健康板块研发的主体单位，索普兴大主要从事药物临床前、临床研究，并承担通盈集团临床试验和新药注册的全部任务。除此之外，通盈集团医药健康板块还拥有博晖生物制药(河北)有限公司、博晖生物制药股份有限公司、云南通盈药业有限公司、昆明贵研药业有限公司、云南通灏生物科技股份有限公司、云南汉创生物科技有限公司、通盈药业(青岛)有限公司等多家公司。 2019年，云南通盈药业有限公司在昆明高新区投资建设生物医药研发及生产基地，以承接TP21原料药和制剂及其他铂类抗肿瘤原料药的研发及生产，实现铂类抗肿瘤原料药国内市场占有率将达到75%，将建成我国规模最大、品种最全、实力最强的铂类抗肿瘤药研发及生产基地。项目分为两期建设，其中项目一期于2023年初完成竣工验收并通过铂类原料药GMP现场检查，已正式投产运营。此外，2021年，通盈集团与青岛巨峰科技创业投资有限公司就“青岛生物医药协同创新中心”项目正式签约，以建设涵盖新药研发全链条环节的四大中心——新药发现中心、国家级药物安全评价中心、药物代谢评价中心、高端制剂中心。截至目前，通盈集团已成功构建了集药物研发、临床试验、新药注册、生产制造及高端技术研发于一体的完整医药产业体系，形成了从研发前端到生产后端的全链条布局。凭借通盈集团完整的产业化生态链，索普兴大将发挥自身研发创新优势，快速推进TP21注射液的3期临床试验，并预计于2026年推进TP21注射液上市进程。届时，TP21注射液将能够快速迈向商业化快车道，实现商业化落地。目前，全球癌症病例正在逐渐上升。根据世界卫生组织国际癌症研究机构（IARC）发布的数据，2022年，全球约有2000万新发癌症病例和970万癌症死亡病例。随着人口老龄化与人口数量的增长及风险因素的变化，预计到2050年，全球癌症新发将超过3500万例，全球癌症负担将进一步增加[9]。从国内数据看，国家癌症中心2022年最新数据表明，2022年中国新增癌症病例高达482.47万例。其中，新增肝癌患者达36.77万例，死亡病例达31.65万例。肝癌的发病和死亡人数在各类癌症中均位列前五[10]。庞大的患者群体背后，是持续增长的治疗需求。而作为肿瘤治疗中的基石类药物，铂类药物至今依然是患者治疗中的关键药物之一。根据QYResearch发布的报告，2022年全球铂类抗癌药市场规模大约为100亿元，预计2029年将达到116亿元，2023-2029期间年复合增长率（CAGR）为2.1%[11]。对此，索普兴大的TP21注射液将以独特优势与广阔潜力切入这一百亿市场，并有望填补铂类药物市场的空白，为患者提供更加精准、有效的治疗方案。在此基础上，索普兴大将围绕TP21生命研发全周期，加大创新投入，深入链接产品研发上下游，以开发并拓展产品的应用潜力。因此，在未来，索普兴大将发挥TP21广谱、低交叉耐药等优势，探索其在肺癌、前列腺癌等其他肿瘤治疗中的潜力，以拓展产品适应症范围。同时，公司拟研发第二代TP21脂质体微球载药技术或反向温控栓塞剂，开发新一代栓塞材料。索普兴大正在寻找有研发需求和特色实力的企业合作，共同推动TP21注射液的商业化落地以及新适应症开发。如果您对该产品感兴趣，欢迎扫描下方二维码与我们取得联系。 * 参考资料： 1. 铂类药物临床应用与不良反应管理专家共识. 今日药学, 2019. 29(09): 577-585. 2. Y. XuQing, J. XiangLin, S. QinHua, et al., Structural studies of dicycloplatin, an antitumor supramolecule.SCIENCE CHINA Chemistry, 2010. 53(6): 1346 - 1351. 3. 张洁, 耕耘在自主创新的道路上——记抗癌新药双环铂主要发明人杨旭清教授攀登历程. 科学中国人, 2008(03): 8-13. 4. G.Q. Li, X.G. Chen, X.P. Wu, et al., Effect of dicycloplatin, a novel platinum chemotherapeutical drug, on inhibiting cell growth and inducing cell apoptosis.PLoS One, 2012. 7(11): e48994. 5. 闫长会, 施畅, 李玉凤, 等., 新铂类药物双环铂与顺铂、卡铂体内毒性的比较研究. 中国新药杂志, 2005(10): 36-39. 6. K.J. Liu, Z.Z. Guan, Y. Liang, et al., A double-blind, randomized phase II study of dicycloplatin plus paclitaxel versus carboplatin plus paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancers.Arch Med Sci, 2014. 10(4): 717-24. 7. H.D. Zhu, X. Li, J.S. Ji, et al., TACE with dicycloplatin in patients with unresectable hepatocellular carcinoma: a multicenter randomized phase II trial.Eur Radiol, 2022. 32(11): 7335-7343. 8. 张爽, 陈孟莉, 尹红, 等., 双环铂治疗恶性肿瘤疗效和安全性回顾性分析. 药学实践杂志, 2020. 38(02): 179-183. 9. IARC. Global cancer burden growing, amidst mounting need for services. 2024; Available from:https://www-who-int.libproxy1.nus.edu.sg/news/item/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services. 10. B. Han, R. Zheng, H. Zeng, et al., Cancer incidence and mortality in China, 2022.J Natl Cancer Cent, 2024. 4(1): 47-53. 11. QYResearch. 2023-2029全球及中国铂类抗癌药行业研究及十四五规划分析报告. 2023; Available from: https://cn.qyresearch.com/reports/1811541/platinum-based-anticancer-drugs. *封面来源：123rf 近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

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适应症	国家/地区	公司	日期
小细胞肺癌	中国	北京索普兴大医药研究有限公司	2012-05-28

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适应症	最高研发状态	国家/地区	公司	日期
前列腺腺癌	临床2期	中国	北京索普兴大医药研究有限公司	2017-08-18
前列腺腺癌	临床2期	中国	北京市兴大科学系统公司	2017-08-18
转移性去势抵抗性前列腺癌	临床2期	中国	北京索普兴大医药研究有限公司	2017-08-18
转移性去势抵抗性前列腺癌	临床2期	中国	北京市兴大科学系统公司	2017-08-18

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO_GU2024	N/A	膀胱尿路上皮癌新辅助	-	Dicycloplatin	願製襯膚積顧鏇壓鹹衊(獵獵製襯鏇夢繭衊積艱) = 鑰選鹽鏇觸夢願遞繭鏇築鹹蓋壓蓋顧襯襯廠衊 (選繭觸觸鑰鏇廠獵觸夢 )	-	2024-01-25