The objective of this study is to apply advanced diffusion imaging in a two-pronged assessment of renal mass patients: (1) characterization of lesion malignancy and subtype, and (2) prediction of renal function stability or decline following partial nephrectomy.

开始日期2022-12-01

申办/合作机构

NYU Langone Health

[+1]

NCT02450279

/ TerminatedN/AIIT

Scintigraphic Comparison of Lung Deposition With Two Nebulizers During Invasive Mechanical Ventilation

Many devices are available for nebulising drug solution during invasive mechanical ventilation. Vibrating-mesh nebulizers ensure the highest lung deposition output. A recent international survey on aerosol therapy during mechanical ventilation (Ehrmann et al. 2013) reported that jet nebulizers remained the mostly used.
The aim of this study is to compare lung deposition of a radiolabeled administered with both nebulizers during invasive mechanical ventilation by planar scintigraphy.

开始日期2016-03-01

申办/合作机构

Cliniques Universitaires Saint-Luc

NCT02429817

/ CompletedN/AIIT

Tomographic Comparison of Aerosol Lung Distribution With Two Nebulizers Through a High Flow Nasal Cannula

Vibrating-mesh nebulizers ensure currently the best deposition output and are recommended in routine use in intensive care unit. However, jet nebulizers remain the most frequently used nebulizers.
On a bench study, aerosol delivery through a high flow nasal cannula (HFNC) was increased using a vibrating-mesh nebulizer as compared to a jet nebulizer.
Lung distribution of nebulized particles delivered through a HFNC has never been investigated in vivo. The aim of this study was to compare aerosol lung distribution with both nebulizers through a HFNC by SPECT-CT.

开始日期2015-04-01

申办/合作机构

Cliniques Universitaires Saint-Luc

100 项与锝[99mTc]喷替酸盐相关的临床结果

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100 项与锝[99mTc]喷替酸盐相关的转化医学

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项与锝[99mTc]喷替酸盐相关的文献（医药）

2025-02-01·Journal of Stroke & Cerebrovascular Diseases

The stroke meta-metric, Defect-Free Care, was maintained year-over-year within the Florida stroke registry during the COVID-19 pandemic

Article

作者: Gardener, Hannah ; Alkhachroum, Ayham ; de Jesus, Daniel M Reyes ; Schutt, Charles ; Romano, Jose G ; Ying, Hao ; Rose, David Z ; Jameson, Angus ; Koch, Sebastian ; Rundek, Tatjana ; Zhou, Lili ; Gutierrez, Carolina M ; Asdaghi, Negar ; Johnson, Karlon H ; Foster, Dianne

BACKGROUND:

Resource allocation for stroke care was impacted worldwide by the Coronavirus 2019 (COVID19) pandemic. Regionally, worsened stroke outcomes varied, however comparative year-over-year in-hospital performance metrics from the pandemic are unreported. Therefore, within the large Florida Stroke Registry (FSR), we assessed the pandemic's effects upon the American Heart Association (AHA) Get With The Guidelines (GWTG) ischemic stroke metrics and the meta-metric, Defect-Free Care (DFC).

METHODS:

From March 2017 to February 2021, FSR collected 146,593 patients with a diagnosis of ischemic stroke or TIA (31,940 between 2017-2018; 35,086 between 2018-2019; 39,722 between 2019-2020; 39,845 between 2020-2021). FSR evaluated DFC, intravenous thrombolytic (IVT) use, endovascular therapy (EVT) use, and Door-To-Needle (DTN), Door-To-Computed Tomography (DTCT), and Door-To-Puncture (DTP) times.

RESULTS:

Pre-pandemic versus pandemic stroke patients' demographics were similar (49.0 % vs. 48.6 % female, age 70.7±14.3 vs. 70.5±14.1 years, 64.0 % vs. 65.3 % white, 18.6 % vs. 18.8 % black, 17.4 % vs. 16.0 % Hispanic). Pandemic strokes, versus the immediate year pre-pandemic, were significantly more severe (median NIHSS 4 [IQR 8] vs. 3 [7]), utilized emergency medical services more (59.2 % vs. 57.6 %) and were more likely to receive EVT (8.0 % vs. 7.0 %). IVT use, and DTCT and DTP times were unchanged. The meta-metric DFC improved year-over-year, albeit slower during the pandemic [2017/18-2018/19: 70.7 % to 74.9 % (+4.2 %); 2018/19-2019/20: 74.9 % to 82.1 % (+7.2 %); 2019/20-2020/21: 82.1 % to 85.2 % (+3.1 %)].

CONCLUSIONS:

Despite pandemic challenges, the stroke meta-metric DFC improved, albeit more slowly than pre-pandemic years. In this large statewide registry, pandemic patients received EVT more, potentially due to more severe stroke presentations. Stroke care infrastructure preparedness for future pandemics is warranted.

2025-01-02·Natural product research

Preparation, structural characteristics and antioxidant activity of polysaccharide and its metal chelates from the peel of Dioscorea oppositifolia L

Article

作者: Wang, Li ; Ma, Bing-Ji ; Niu, Chao-Fei ; Li, Hui ; Wang, Yi ; Ruan, Yuan ; Liu, Yi

Two metal chelates of Dioscorea oppositifolia L. peel polysaccharides (DTP) were prepared: iron chelate (DTP-Fe) and zinc chelate (DTP-Zn). The physicochemical properties of the polysaccharide and its metal chelates were assessed by UV-Vis absorption spectroscopy, Fourier-transform infra-red spectroscopy, scanning electron microscopy, and thermogravimetric analysis. Antioxidant activities were evaluated by DPPH, ABTS + and hydroxyl radical scavenging assays. According to ICP-MS, the iron content of DTP-Fe was 9.47%, while the zinc content of DTP-Zn was 4.02%. The antioxidant capacity of DTP-Fe increased with the increase of concentration, and its overall activity was higher than that of DTP and DTP-Zn. This polysaccharide-iron chelate can be developed and utilised as an antioxidant and multifunctional iron supplement. DTP-Zn showed the potential to be a natural antioxidant and zinc supplement food.

2025-01-01·VACCINE

The trend in national childhood immunization program coverage throughout Serbian communities in Kosovo and Metohija from 2003 to 2022: pre-COVID-19 period vs. COVID-19 pandemic

Article

作者: Stevanovic, Jasmina ; Kovacevic, Milica ; Subaric, Aleksandar ; Gazibara, Tatjana ; Antonijevic, Aleksandar ; Stosic, Maja ; Subaric, Ljiljana ; Milic, Marija ; Dotlic, Jelena ; Filimonovic, Jelena ; Mijovic, Biljana ; Radulovic, Jana ; Radulovic, Aleksandra ; Joksimovic, Bojan

BACKGROUND:

The childhood immunization coverage in Serbian communities in Kosovo after the 1999 armed conflict has not been investigated. The study purpose was to evaluate the trend of immunization coverage with vaccines from the national childhood immunization program in Serbian communities in Kosovo and Metohija from 2003 to 2022.

METHODS:

Data were retrieved from the annual reports of the Public Health Institute of Kosovska Mitrovica received through notifications from the primary health centers where vaccines are being administered. Data were analyzed using the linear regression and join-point regression models.

RESULTS:

In the examined period, a significant decrease in vaccination coverage was observed for the following diseases: diphtheria, tetanus and pertussis (DTP), polio, as well as measles, mumps and rubella vaccines (MMR), then, the first revaccination for DTP and polio, the second revaccination against diphtheria and tetanus for children (DT) and polio, and the third revaccination against diphtheria and tetanus for adults (dT), as well as the second dose of the MMR vaccine. During the COVID-19 pandemic, a significant decrease in coverage was observed for primary vaccination against: DTP, polio and hepatitis B, first and second doses of the MMR vaccine, as well as the first and second revaccination for DTP and polio, and the third revaccination for dT.

CONCLUSION:

A decline in coverage with DTP, MMR, polio and hepatitis B vaccines was observed between 2003 and 2022. This was even more pronounced during the COVID-19 pandemic. Further research on individual-level factors contributing to lower vaccination coverage is warranted.

项与锝[99mTc]喷替酸盐相关的新闻（医药）

2024-09-29

·药事纵横

生物制剂中“明星”表面活性剂——吐温80

介绍：聚山梨酯（吐温，PS）是一类两亲性非离子表面活性剂家族，其中，聚山梨酸酯80（吐温80）是生物药物制剂中使用最广泛的“明星”表面活性剂，可防止蛋白质在储存、运输条件变性、聚集、表面吸附以及絮凝作用。吐温80是一种混合物，主要成分是聚氧乙烯脱水山梨糖醇单油酸酯。作为常用的药物辅料，市售注射用吐温80主要有MC（多药典级）和CP（中国药典级）两种级别，其主要差异在油酸含量上，见表1。其中，CP级别常用供应商日油和南京威尔，MC级别有JT、Sigma和禾大等。吐温80可以通过氧化和水解途径降解，见图1，其中水解反应是化学诱导的或酶催化的，氧化反应一般由化学诱导。吐温80作为生物制剂的一种保护剂辅料使用，但也可能影响蛋白质制剂的质量，从而对功效、安全性和稳定性起到不利作用。目前，药品监管部门对吐温80的控制要求越来越严格。图1 吐温80的主要降解途径有很多学者对吐温80进行了大量研究，下面从吐温80的优缺点、含量测定方法、以及面临挑战几个方面进行介绍。吐温80的优点： PS80是生物制剂中最常用的表面活性剂，在大多数商业治疗性蛋白质制剂中用作蛋白质稳定剂。这是由于以下因素： 1）生物相容性高； 2）低毒性； 3）有效的蛋白质稳定作用。即使在低浓度下（生物制剂中常用浓度为0.1-1.0mg/ml），它们也提供了足够的蛋白质稳定性。这是由于PS80的亲水亲脂平衡（HLB）值高和临界胶束浓度（CMC）低，PS80的CMC仅为1.4*10-2g/L。蛋白质具有天然的不稳定性，易受到外部条件的影响，如温度、震荡、剪切力、缓冲体系及离子强度等，甚至自身的蛋白浓度或纯度的改变。其中，所有蛋白质变性降解的问题中，聚集的问题尤为严重。下游的制剂开发中常常使用吐温80作为蛋白的保护剂。聚山梨酯稳定蛋白质的机理，通常认为界面竞争和表面活性剂-蛋白质复合这两种主要机理。吐温80主要通过界面竞争作用来稳定蛋白质，吐温80的表面活性比蛋白质（即单克隆抗体（mAbs））高很多，因此，吐温80可以竞争性地占据界面位置，抑制蛋白质吸附到气液交界面，进而减少与空气接触造成的氧化或聚集，也有效防止蛋白质在制造过程、样品处理和存储中在界面处展开。吐温80还可以通过与蛋白质直接相互作用，增加蛋白质的胶体稳定性。抗体可能会通过其分子间输水作用形成聚集体。吐温80可通过与蛋白质表面上的疏水相互作用，从而防止蛋白质聚集甚至颗粒的产生。吐温80的缺点：前面提到吐温80其实是一种混合物，市售的预期结构聚氧乙烯脱水山梨糖醇单油酸酯）仅占吐温80总量的20％。如图2所示，异质性主要来来源与工艺相关的副产物杂质，其中不仅含有单酯（预期结构），还含有二酯、多酯，甚至未成酯的脂肪酸链。此外，前面还提到（见图1），吐温80可以发生水解反应及氧化反应导致降解，产生脂肪酸链及氧化物，以上导致对吐温80的表征成为了难点。图2 吐温80主要的化学结构吐温80的表征：吐温80的结构缺乏强发色团，无法直接检测到容易获得的紫外可见光及荧光。目前，很多研究学者已经开发了多种表征方法来控制吐温80的不同性质，表2总结了几种常见含量检测方法的原理及优缺点。然而，由于不同亚种（如未酯化、单酯、多酯）及降解产物（如水解、氧化）对总吐温80含量结果的贡献值存在显著差异，因此用不同原理方法测定的吐温80含量显示出明显的差异。此外，还采用MS或CAD（其中主要应用色谱与MS联合应用）来分析主要吐温80亚种的组成及降解物，例如小的有机分子，游离脂肪酸等，研究解聚山梨酯降解途径。药典方法、HPLC-ELSD/CAD方法对水解产物较为敏感，HPLC-FMA也可测出样品水解，然而测定吐温80氧化方面上，FMA方法更胜一筹，综合来看，HPLC-FMA方法更适用于PS80含量的检测。截止目前为止，吐温80的表征方法层出不穷，但具有各自方法的优点及弊端，其仍然是一项分析挑战，必要时可采取多种检测方式共同评价。面临的挑战：吐温80的水解也就是酯的水解，反应生成的游离脂肪酸链可形成聚集甚至可见颗粒，并且可能与蛋白结合形成脂肪酸-蛋白复合物。在典型的蛋白质制剂pH（4-7）下，吐温80的水解受到限制。有文献表明，酶诱导的吐温80水解是影响产品质量的可见和亚可见颗粒形成的主要原因，实际生产中上游工艺带来的Hcp脂肪酶是催化PS80水解的一个重要因素，其具有与目标蛋白相似的理化性质，因此很难完全去除。即使优化纯化工艺去除Hcp，但远低于检测限的极少量Hcp（ppm级别）也可催化PS80的水解。吐温80可能被光照、温度，过氧化物、氧气或痕量金属离子等影响因素氧化，氧化位置常见脂肪酸链双键、母核的醚键和部分酯键，降解产物有自由基、过氧化物、游离脂肪酸、短链烷烃、醛、酮、酸等。而生成的过氧化物可能继而引起蛋白质氧化。泊洛沙姆188（P188）是另一种在蛋白质制剂中用作蛋白质稳定剂的赋形剂，尽管不如吐温80使用广泛。P188因不具备酯键，不会有发生水解的风险，主要通过氧化形式在溶液中降解，形成氧化的聚氧乙烯（POE）和聚环氧丙烷（PPO）。但P188在上市品种中应用局限，可能存在长期放置过程中潜在风险。因此，推荐使用一些手段减少吐温对蛋白质的负面影响，如2-8℃低温储存、充氮、避光保护；通过上游工艺优化降低Hcp；加入抗氧化剂、金属络合剂等。其中抗氧化剂如甲硫氨酸、赖氨酸、色氨酸等，金属络合剂如EDTA、DTPA等。参考文献： [1] Characterization of Polysorbate 80 by Liquid Chromatography Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway Journal of Pharmaceutical Sciences 111 (2022) 323−334; [2] Characterization of Polysorbate Ester Fractions and Implications in Protein Drug Product Stability Mol. Pharmaceutics 2020, 17, 2345−2353; [3] Degradation of polysorbates 20 and 80 catalysed by histidine chloride buffer European Journal of Pharmaceutics and Biopharmaceutics 154 (2020) 236–245. 药事纵横投稿须知：稿费已上调，欢迎投稿

2024-06-11

·PRNewswire

Global Anti-Radiation Drugs Market to Register Incremental Growth at a CAGR of ~9% by 2030 | DelveInsight

The rise in demand for anti-radiation drugs is mainly driven by several factors. These include the growing occurrence of side effects linked to cancer screening methods, heightened risks of exposure to radiological or nuclear emergencies, and the increasing focus of nuclear-capable nations on safeguarding against radiation. These trends are expected to fuel the expansion of the anti-radiation drugs market from 2024 to 2030. LAS VEGAS, June 11, 2024 /PRNewswire/ -- DelveInsight's Anti-Radiation Drugs Market Insights report provides the current and forecast market analysis, individual leading anti-radiation drugs companies' market shares, challenges, anti-radiation drugs market drivers, barriers, trends, and key market anti-radiation drugs companies in the market. Key Takeaways from the Anti-Radiation Drugs Market Report As per DelveInsight estimates, North America is anticipated to dominate the global anti-radiation drugs market during the forecast period. In the compound type segment of the anti-radiation drugs market, the Potassium iodide sub-category had a significant revenue share in the year 2023. This can be ascribed to the various characteristics and advantages associated with potassium iodide. Notable anti-radiation drugs companies such as Novartis AG, Anbex Inc., Amgen Inc., Myelo Therapeutics, Arco Pharmaceuticals LLC, BTG International Inc., Cellphire Inc., Darnitsa, Enzychem Lifesciences Corporation, Humanetics Corporation, Mission Pharmacal Company, Chrysalis BioTherapeutics Inc., Pluri Inc., Partner Therapeutics, HEYL Chemisch-pharmazeutische Fabrik GmbH & Co. KG., RxBio Inc., Coherus Biosciences, Onconova Therapeutics, Jubilant Life Sciences, Soligenix Inc., and several others, are currently operating in the anti-radiation drugs market. In September 2023, the U.S. Department of Defense awarded Edina-based Humanetics a USD 20 million contract to develop a pill that prevents radiation damage in military members and first responders affected by events such as nuclear accidents, warfare, and dirty bombs. In May 2023, the first-in-human clinical trial of an experimental oral drug for removing radioactive contaminants from inside the body, testing the safety, tolerability, and processing in the body of escalating doses of the investigational drug product HOPO 14-1 was initiated in healthy adults. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, was funding the Phase 1 trial, which was sponsored and conducted by SRI International of Menlo Park, California. In March 2022, Novartis announced that the US Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for the treatment of adult patients with a certain type of advanced cancer called prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer (PSMA-positive mCRPC) that has spread to other parts of the body. These patients have already been treated with other anticancer treatments (androgen receptor pathway inhibition and taxane-based chemotherapy). To read more about the latest highlights related to the anti-radiation drugs market, get a snapshot of the key highlights entailed in the Global Anti-Radiation Drugs Market Report Anti-Radiation Drugs Overview Anti-radiation drugs are pharmaceutical compounds designed to mitigate the damaging effects of radiation exposure on the human body. These drugs work by either scavenging free radicals generated by radiation or by enhancing the repair mechanisms of cells damaged by radiation. One class of anti-radiation drugs includes radioprotectors, which are administered before radiation exposure to prevent or reduce its harmful effects. Another class, known as radiomitigators, is given after exposure to alleviate the severity of radiation-induced damage. These drugs hold significant promise in scenarios such as nuclear accidents, medical radiation therapy, and space travel, where the risk of radiation exposure is a concern. Research into anti-radiation drugs is ongoing, with scientists continually striving to improve their efficacy and minimize side effects. Some compounds under investigation show potential not only in protecting against acute radiation sickness but also in mitigating long-term effects such as cancer development. As our understanding of radiation biology advances, coupled with advancements in drug development technologies, the prospects for more effective and accessible anti-radiation drugs continue to brighten, offering hope for safer environments in radiation-prone situations. Anti-Radiation Drugs Market Insights In 2023, North America dominated the anti-radiation drugs market, primarily due to several factors contributing to growth. These include a substantial patient population afflicted with various illnesses like cancer, increasing numbers of diagnostic procedures, and governmental initiatives aimed at public health in the region. This trend is expected to continue from 2024 to 2030. The prevalence of cancer in the United States, for example, drives a significant demand for anti-radiation drugs. Statistics from the American Cancer Society projected around 2 million new cancer cases in the United States in 2024, leading to heightened demand for these drugs to support cancer diagnostic procedures. Additionally, the US benefits from a strong focus on clinical research and the presence of leading pharmaceutical companies, further bolstering the market for anti-radiation drugs. Moreover, in 2022, the US Department of Health and Human Services (HHS) allocated USD 290 million for the purchase of Nplate, a drug produced by Amgen USA Inc., intended to treat radiation sickness in the event of a nuclear emergency. This investment reflects ongoing efforts to enhance preparedness for radiological and nuclear emergencies and underscores the commitment to saving lives in such scenarios. To know more about why North America is leading the market growth in the anti-radiation drugs market, get a snapshot of the Anti-Radiation Drugs Market Outlook Anti-Radiation Drugs Market Dynamics The market dynamics of anti-radiation drugs are driven by a complex interplay of factors ranging from technological advancements to geopolitical events and regulatory frameworks. One of the primary drivers is the increasing threat of radiation exposure from various sources such as nuclear accidents, medical procedures, and potential radiological terrorism. This heightened awareness has propelled research and development efforts to create effective anti-radiation drugs that can mitigate the harmful effects of radiation exposure. Moreover, the growing prevalence of cancer and the widespread use of radiation therapy as a treatment modality has further fueled the demand for anti-radiation drugs. As more individuals undergo radiation-based treatments, there is a parallel need for medications that can protect healthy tissues and organs from the damaging effects of ionizing radiation. The competitive landscape of the anti-radiation drugs market is characterized by both established pharmaceutical companies and innovative startups vying for market share. Established players often leverage their resources and expertise to develop and commercialize new anti-radiation drugs, while startups focus on disruptive technologies and novel approaches to address unmet needs in radiation protection. Government initiatives and regulatory frameworks also play a crucial role in shaping the market dynamics of anti-radiation drugs. Regulatory agencies set standards for safety, efficacy, and quality assurance, which impact the development, approval, and commercialization of these medications. Additionally, government investments in research and development, as well as funding for procurement and stockpiling of anti-radiation drugs for emergency preparedness, influence market dynamics. Overall, the anti-radiation drugs market is characterized by a dynamic landscape driven by technological innovation, healthcare trends, regulatory factors, and geopolitical considerations. As the threat of radiation exposure continues to evolve, so too will the demand for effective anti-radiation drugs, driving further growth and innovation in this important sector of the pharmaceutical industry. Get a sneak peek at the anti-radiation drugs market dynamics @ Anti-Radiation Drugs Market Dynamics Analysis Anti-Radiation Drugs Market Assessment Anti-Radiation Drugs Market Segmentation Anti-Radiation Drugs Market Segmentation By Compound: Potassium Iodide, Prussian Blue, Diethylenetriamine Pentaacetic Acid, Colony Stimulating Factors, and Others Anti-Radiation Drugs Market Segmentation By Indication: Acute Radiation Syndrome, Cancer Treatment, and Others Anti-Radiation Drugs Market Segmentation By Radiation Type: Ionizing Radiations and Non-Ionizing Radiations Anti-Radiation Drugs Market Segmentation By Distribution Channel: Hospital Pharmacies, Retail Pharmacies, and Others Anti-Radiation Drugs Market Segmentation By Geography: North America, Europe, Asia-Pacific, and Rest of World Porter's Five Forces Analysis, Product Profiles, Case Studies, KOL's Views, Analyst's View Which MedTech key players in the anti-radiation drugs market are set to emerge as the trendsetter explore @ Anti-Radiation Drugs Companies Table of Contents Interested in knowing the anti-radiation drugs market by 2030? Click to get a snapshot of the Anti-Radiation Drugs Market Trends Related Reports Cancer Biomarkers Market Cancer Biomarkers Market Insight, Competitive Landscape, and Market Forecast – 2030 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key cancer biomarkers companies, including F. Hoffmann-La Roche Ltd., Thermo Fisher Scientific, Inc., QIAGEN N.V., Illumina, Inc., Bio-Rad Laboratories, Inc., Abbott Laboratories, bioMérieux SA, BD, Merck Millipore, Agilent Technologies, Myriad Genetics, Sysmex Corporation, Hologic, Inc., Quest Diagnostics, Centogene N.V., PerkinElmer, Inc., Siemens Healthineers, Exact Sciences, R&D Systems, Inc., BioVision, Inc., among others. 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Hoffman La Roche Ltd, Guardant Health, Bio-Techne, Illumina Inc, QIAGEN, Lucence Health Inc, Personal Gemone Diagnostics Inc, SAGA Diagnostics, Agena Bioscience Inc, The Menarini Group, MiRXES Pte Ltd., among others. About DelveInsight DelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

放射疗法

2022-12-24

·药通社

生物制剂中“明星”表面活性剂——吐温80

介绍：聚山梨酯（吐温，PS）是一类两亲性非离子表面活性剂家族，其中，聚山梨酸酯80（吐温80）是生物药物制剂中使用最广泛的“明星”表面活性剂，可防止蛋白质在储存、运输条件变性、聚集、表面吸附以及絮凝作用。吐温80是一种混合物，主要成分是聚氧乙烯脱水山梨糖醇单油酸酯。作为常用的药物辅料，市售注射用吐温80主要有MC（多药典级）和CP（中国药典级）两种级别，其主要差异在油酸含量上，见表1。其中，CP级别常用供应商日油和南京威尔，MC级别有JT、Sigma和禾大等。吐温80可以通过氧化和水解途径降解，见图1，其中水解反应是化学诱导的或酶催化的，氧化反应一般由化学诱导。吐温80作为生物制剂的一种保护剂辅料使用，但也可能影响蛋白质制剂的质量，从而对功效、安全性和稳定性起到不利作用。目前，药品监管部门对吐温80的控制要求越来越严格。图1 吐温80的主要降解途径有很多学者对吐温80进行了大量研究，下面从吐温80的优缺点、含量测定方法、以及面临挑战几个方面进行介绍。吐温80的优点：PS80是生物制剂中最常用的表面活性剂，在大多数商业治疗性蛋白质制剂中用作蛋白质稳定剂。这是由于以下因素：1）生物相容性高；2）低毒性；3）有效的蛋白质稳定作用。即使在低浓度下（生物制剂中常用浓度为0.1-1.0mg/ml），它们也提供了足够的蛋白质稳定性。这是由于PS80的亲水亲脂平衡（HLB）值高和临界胶束浓度（CMC）低，PS80的CMC仅为1.4*10-2g/L。蛋白质具有天然的不稳定性，易受到外部条件的影响，如温度、震荡、剪切力、缓冲体系及离子强度等，甚至自身的蛋白浓度或纯度的改变。其中，所有蛋白质变性降解的问题中，聚集的问题尤为严重。下游的制剂开发中常常使用吐温80作为蛋白的保护剂。聚山梨酯稳定蛋白质的机理，通常认为界面竞争和表面活性剂-蛋白质复合这两种主要机理。吐温80主要通过界面竞争作用来稳定蛋白质，吐温80的表面活性比蛋白质（即单克隆抗体（mAbs））高很多，因此，吐温80可以竞争性地占据界面位置，抑制蛋白质吸附到气液交界面，进而减少与空气接触造成的氧化或聚集，也有效防止蛋白质在制造过程、样品处理和存储中在界面处展开。吐温80还可以通过与蛋白质直接相互作用，增加蛋白质的胶体稳定性。抗体可能会通过其分子间输水作用形成聚集体。吐温80可通过与蛋白质表面上的疏水相互作用，从而防止蛋白质聚集甚至颗粒的产生。吐温80的缺点：前面提到吐温80其实是一种混合物，市售的预期结构聚氧乙烯脱水山梨糖醇单油酸酯）仅占吐温80总量的20％。如图2所示，异质性主要来来源与工艺相关的副产物杂质，其中不仅含有单酯（预期结构），还含有二酯、多酯，甚至未成酯的脂肪酸链。此外，前面还提到（见图1），吐温80可以发生水解反应及氧化反应导致降解，产生脂肪酸链及氧化物，以上导致对吐温80的表征成为了难点。图2 吐温80主要的化学结构吐温80的表征：吐温80的结构缺乏强发色团，无法直接检测到容易获得的紫外可见光及荧光。目前，很多研究学者已经开发了多种表征方法来控制吐温80的不同性质，表2总结了几种常见含量检测方法的原理及优缺点。然而，由于不同亚种（如未酯化、单酯、多酯）及降解产物（如水解、氧化）对总吐温80含量结果的贡献值存在显著差异，因此用不同原理方法测定的吐温80含量显示出明显的差异。此外，还采用MS或CAD（其中主要应用色谱与MS联合应用）来分析主要吐温80亚种的组成及降解物，例如小的有机分子，游离脂肪酸等，研究解聚山梨酯降解途径。药典方法、HPLC-ELSD/CAD方法对水解产物较为敏感，HPLC-FMA也可测出样品水解，然而测定吐温80氧化方面上，FMA方法更胜一筹，综合来看，HPLC-FMA方法更适用于PS80含量的检测。截止目前为止，吐温80的表征方法层出不穷，但具有各自方法的优点及弊端，其仍然是一项分析挑战，必要时可采取多种检测方式共同评价。面临的挑战：吐温80的水解也就是酯的水解，反应生成的游离脂肪酸链可形成聚集甚至可见颗粒，并且可能与蛋白结合形成脂肪酸-蛋白复合物。在典型的蛋白质制剂pH（4-7）下，吐温80的水解受到限制。有文献表明，酶诱导的吐温80水解是影响产品质量的可见和亚可见颗粒形成的主要原因，实际生产中上游工艺带来的Hcp脂肪酶是催化PS80水解的一个重要因素，其具有与目标蛋白相似的理化性质，因此很难完全去除。即使优化纯化工艺去除Hcp，但远低于检测限的极少量Hcp（ppm级别）也可催化PS80的水解。吐温80可能被光照、温度，过氧化物、氧气或痕量金属离子等影响因素氧化，氧化位置常见脂肪酸链双键、母核的醚键和部分酯键，降解产物有自由基、过氧化物、游离脂肪酸、短链烷烃、醛、酮、酸等。而生成的过氧化物可能继而引起蛋白质氧化。泊洛沙姆188（P188）是另一种在蛋白质制剂中用作蛋白质稳定剂的赋形剂，尽管不如吐温80使用广泛。P188因不具备酯键，不会有发生水解的风险，主要通过氧化形式在溶液中降解，形成氧化的聚氧乙烯（POE）和聚环氧丙烷（PPO）。但P188在上市品种中应用局限，可能存在长期放置过程中潜在风险。因此，推荐使用一些手段减少吐温对蛋白质的负面影响，如2-8℃低温储存、充氮、避光保护；通过上游工艺优化降低Hcp；加入抗氧化剂、金属络合剂等。其中抗氧化剂如甲硫氨酸、赖氨酸、色氨酸等，金属络合剂如EDTA、DTPA等。参考文献：[1] Characterization of Polysorbate 80 by Liquid Chromatography Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway Journal of Pharmaceutical Sciences 111 (2022) 323−334;[2] Characterization of Polysorbate Ester Fractions and Implications in Protein Drug Product Stability Mol. Pharmaceutics 2020, 17, 2345−2353;[3] Degradation of polysorbates 20 and 80 catalysed by histidine chloride buffer European Journal of Pharmaceutics and Biopharmaceutics 154 (2020) 236–245.药事纵横投稿须知：稿费已上调，欢迎投稿各位朋友好，觉得本文对您有帮助，请随手点一下下方的在看，以便让你的朋友也能看到哦。

100 项与锝[99mTc]喷替酸盐相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	锝[99mTc]喷替酸盐	-	DB14007

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肺部疾病	美国	Jubilant Draximage, Inc.初创企业	2017-12-26
脑疾病	美国	Jubilant Draximage, Inc.初创企业	1989-12-29
肾脏疾病	日本	PDRadiopharma, Inc.	1979-05-22

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肿瘤	临床1期	-	University of California San Diego	-

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临床结果

适应症

分期

评价

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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


SNMMI2022	N/A	肾积水	-	99mTc-DTPA (Mild hydronephrosis group)	製餘製積蓋繭願鏇遞蓋(廠製繭鑰蓋淵選構齋夢) = 獵獵範構願選鬱簾廠壓築範築積鹹衊鬱艱糧醖 (觸憲遞製願構醖淵鏇繭 ) 更多	-	2022-08-08
				99mTc-DTPA (Moderate hydronephrosis group)	製餘製積蓋繭願鏇遞蓋(廠製繭鑰蓋淵選構齋夢) = 選範鹽鏇襯簾艱淵選淵築範築積鹹衊鬱艱糧醖 (觸憲遞製願構醖淵鏇繭 ) 更多
SNMMI2022	N/A	-	-	99mTc-L,L EC	構鹹餘遞繭鬱壓範範壓(淵餘簾糧齋範範繭鬱艱) = 淵製製製顧膚淵觸獵範廠範憲鬱顧膚觸鹽廠鹽 (醖糧願襯鑰願夢鏇築網, 13.77)	-	2022-08-08
				99mTc-DTPA	構鹹餘遞繭鬱壓範範壓(淵餘簾糧齋範範繭鬱艱) = 鑰鏇齋願廠積憲範衊廠廠範憲鬱顧膚觸鹽廠鹽 (醖糧願襯鑰願夢鏇築網, 16.74)
EANM2021	N/A	-	195	99m Tc-DTPA	壓淵衊蓋遞築顧衊鏇積(衊觸衊鹽鏇鹽衊淵襯構) = 蓋窪糧顧壓餘顧構醖範醖廠簾簾餘顧觸製範顧 (獵憲夢觸餘壓網獵夢築, 19.1)	积极	2021-09-24
				99m Tc-DTPA (MDRD4 equation)	壓淵衊蓋遞築顧衊鏇積(衊觸衊鹽鏇鹽衊淵襯構) = 鹽鏇壓製製製襯鹽鑰鏇醖廠簾簾餘顧觸製範顧 (獵憲夢觸餘壓網獵夢築, 18.82)
ERS2021	N/A	弥漫性硬皮病 KL-6 \| SP-D	58	Tc99m – DTPA aerosols	範鑰網鏇蓋選艱顧糧繭(窪繭鑰簾簾繭衊齋鑰淵) = 遞鏇艱遞繭鹹壓範襯淵顧選鑰膚憲構網鹽鏇網 (鹽壓鑰壓製膚壓築鑰獵, 25.7)	积极	2021-09-05
SNMMI2021	N/A	并发症	-	99m Tc-DTPA (99mTc-DTPA scintigraphy)	鹹艱築膚網獵糧淵窪選(壓壓壓淵獵鹽憲鹹窪網) = 鬱遞糧顧製鹽顧艱築夢窪壓淵壓壓構獵窪壓糧 (醖窪窪淵鬱鑰鏇衊簾夢 ) 更多	-	2021-05-18
EANM2020	N/A	-	30	99mTc-DTPA (Reference Method)	蓋製繭範衊餘遞選窪顧(糧齋遞鑰餘製鬱淵壓繭) = 鹽衊衊鑰鹹範遞願鑰願蓋獵構選鏇製積鏇遞構 (艱夢夢夢衊鹹製齋鑰範 )	积极	2020-09-18
				99mTc-DTPA (Simplified Method 1)	蓋製繭範衊餘遞選窪顧(糧齋遞鑰餘製鬱淵壓繭) = 製膚廠窪遞繭憲獵醖選蓋獵構選鏇製積鏇遞構 (艱夢夢夢衊鹹製齋鑰範 )
EANM2019	N/A	-	42	99mTc-DTPA	夢簾鬱獵夢築鑰膚構鹽(憲遞製襯獵觸顧積範襯) = 願獵廠鏇鏇蓋顧淵網願齋淵網餘糧憲簾願觸鹹 (醖築範簾鏇網窪簾廠襯 ) 更多	-	2019-09-18
				99mTc-DTPA (51Cr-EDTA)	夢簾鬱獵夢築鑰膚構鹽(憲遞製襯獵觸顧積範襯) = 鏇糧壓壓願衊願範襯築齋淵網餘糧憲簾願觸鹹 (醖築範簾鏇網窪簾廠襯 ) 更多
EANM2019	N/A	-	-	51 Cr-EDTA	築簾憲齋鏇壓蓋膚齋築(積網蓋窪鹹鹽築衊築觸) = 範壓繭繭構蓋齋顧餘遞蓋憲醖鏇壓鑰衊糧積窪 (遞遞築膚襯觸積鏇觸鑰, 16 ~ 226)	积极	2019-09-18
EANM2019	N/A	慢性肾病 indoxyl sulfate	-	99mTc-DTPA (Control Group)	鬱構壓積構糧簾鑰鏇齋(繭壓窪選窪艱選醖鏇衊) = 膚憲選製艱壓繭觸夢糧齋齋餘鑰襯範夢衊襯鬱 (窪憲範遞製艱夢範壓壓, 0.01) 更多	-	2019-09-18
				99mTc-DTPA (Adenine rich diet (ARD) rats)	鬱構壓積構糧簾鑰鏇齋(繭壓窪選窪艱選醖鏇衊) = 糧網鹹憲艱網網艱構網齋齋餘鑰襯範夢衊襯鬱 (窪憲範遞製艱夢範壓壓, 0.025) 更多
EANM2019	N/A	serum creatinine concentration	-	99mTc-DTPA (SI-GFR)	網觸積網觸積齋醖鹽遞(願夢夢糧鹹艱齋壓齋醖) = 壓壓憲願廠齋遞膚醖膚夢遞艱鑰襯膚壓鏇築觸 (鹽積鏇膚壓築願鑰製糧, 50.4) 更多	-	2019-09-18
				99mTc-DTPA (SS-GFR)	網觸積網觸積齋醖鹽遞(願夢夢糧鹹艱齋壓齋醖) = 蓋窪憲襯憲鬱餘鹹繭鑰夢遞艱鑰襯膚壓鏇築觸 (鹽積鏇膚壓築願鑰製糧, 53.5) 更多