更新于：2024-06-19
Quinine Hydrochloride Hydrate
盐酸奎宁水合物
更新于：2024-06-19
概要
基本信息
非在研机构- |
最高研发阶段批准上市 |
首次获批日期 日本 (1953-12-01), |
最高研发阶段(中国)批准上市 |
特殊审评- |
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结构
分子式C20H27ClN2O3 |
InChIKeySGVZDMWHXVXUBY-HZQSTTLBSA-N |
CAS号6119-47-7 |
关联
22
项与 盐酸奎宁水合物 相关的临床试验Effect of a 5-HT3 Receptor Antagonist on Respiratory Drive in Spontaneously Breathing Mechanically Ventilated Patients With Acute Respiratory Distress Syndrome (ARDS): a Pilot Proof-of-concept Crossover Non-randomized Controlled Trial
This is a pilot study aimed at acquiring primary physiological data, describing and estimating the effects of a 5-HT3 receptor antagonist (ondansetron) on respiratory drive in patients with acute respiratory distress syndrome (ARDS). The results of this study will determine the interest and feasibility of assessing the clinical applications of ondansetron in reducing patient self-inflicted lung injury (P-SILI) in ARDS, in subsequent studies.
开始日期2022-11-10 |
申办/合作机构 |
Effects of intraduodenal administration of quinine on blood glucose concentrations, gastric emptying, gut and gluco-regulatory hormone release, and gastrointestinal symptoms in humans with type 2 diabetes.
开始日期2020-10-01 |
申办/合作机构- |
Effects of intraduodenal administration of quinine on blood glucose concentrations, gastric emptying, gut and gluco-regulatory hormone release, and gastrointestinal symptoms in healthy females.
开始日期2020-06-01 |
申办/合作机构- |
100 项与 盐酸奎宁水合物 相关的临床结果
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100 项与 盐酸奎宁水合物 相关的转化医学
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100 项与 盐酸奎宁水合物 相关的专利（医药）
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8,073
项与 盐酸奎宁水合物 相关的文献（医药）2024-03-01·Journal of ethnopharmacology
Brazilian plants with antimalarial activity: A review of the period from 2011 to 2022
Review
作者: Veras Mourão, Rosa Helena ; Viana Dos Santos, Maria Beatriz ; Braga de Oliveira, Alaíde
ETHNOPHARMACOLOGICAL RELEVANCE:
Malaria continues to be a serious global public health problem in subtropical and tropical countries of the world. The main drugs used in the treatment of human malaria, quinine and artemisinin, are isolates of medicinal plants, making the use of plants a widespread practice in countries where malaria is endemic. Over the years, due to the increased resistance of the parasite to chloroquine and artemisinin in certain regions, new strategies for combating malaria have been employed, including research with medicinal plants.
AIM:
This review focuses on the scientific production regarding medicinal plants from Brazil whose antimalarial activity was evaluated during the period from 2011 to 2022. 2.
METHODOLOGY:
For this review, four electronic databases were selected for research: Pubmed, ScienceDirect, Scielo and Periódicos CAPES. Searches were made for full texts published in the form of scientific articles written in Portuguese or English and in a digital format. In addition, prospects for new treatments as well as future research that encourages the search for natural products and antimalarial derivatives are also presented.
RESULTS:
A total of 61 publications were encountered, which cited 36 botanical families and 92 species using different Plasmodium strains in in vitro and in vivo assays. The botanical families with the most expressive number of species found were Rubiaceae, Apocynaceae, Fabaceae and Asteraceae (14, 14, 9 and 6 species, respectively), and the most frequently cited species were of the genera Psychotria L. (8) and Aspidosperma Mart. (12), which belong to the families Rubiaceae and Apocynaceae. Altogether, 75 compounds were identified or isolated from 28 different species, 31 of which are alkaloids. In addition, the extracts of the analyzed species, including the isolated compounds, showed a significant reduction of parasitemia in P. falciparum and P. berghei, especially in the clones W2 CQ-R (in vitro) and ANKA (in vivo), respectively. The Brazilian regions with the highest number of species analyzed were those of the north, especially the states of Pará and Amazonas, and the southeast, especially the state of Minas Gerais.
CONCLUSION:
Although many plant species with antimalarial potential have been identified in Brazil, studies of new antimalarial molecules are slow and have not evolved to the production of a phytotherapeutic medicine. Given this, investigations of plants of traditional use and biotechnological approaches are necessary for the discovery of natural antimalarial products that contribute to the treatment of the disease in the country and in other endemic regions.
2024-03-01·Physiology & behavior
Bitter taste function-related genes are implicated in the behavioral association between taste preference and ethanol preference in male mice
Article
作者: Koh, Anna P ; Dando, Robin ; Smith, Molly I
Alcohol use disorder in humans is highly heritable, and as a term is synonymous with alcoholism, alcohol dependence, and alcohol addiction. Defined by the NIAAA as a medical condition characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences, the genetic basis of alcohol dependence is much studied. However, an intriguing component to alcohol acceptance exists outside of genetics or social factors. In fact, mice of identical genetic backgrounds without any prior experience of tasting ethanol display widely varying preferences to it, far beyond those seen for typical taste solutions. Here, we hypothesized that a preference for ethanol, which tastes both bitter and sweet to humans, would be influenced by taste function. Using a mouse model of taste behavior, we tested preferences for bitter and sweet in mice that, without training or previous experience, either preferred or avoided ethanol solutions in consumption trials. Data showed clear sex differences, in which male mice that preferred ethanol also preferred a bitter quinine solution, whereas female mice that preferred ethanol also preferred a sweet sucralose solution. Male mice preferring ethanol also exhibited lower expression levels of mRNA for genes encoding the bitter taste receptors T2R26 and T2R37, and the bitter transducing G-protein subunit GNAT3, suggesting that the higher ethanol preference observed in the male mice may be due to bitter signaling, including that arising from ethanol, being weaker in this group. Results further support links between ethanol consumption and taste response, and may be relevant to substance abuse issues in human populations.
2024-03-01·Molecular and cellular biochemistry
Regulation of Ras p21 and RalA GTPases activity by quinine in mammary epithelial cells
Article
作者: Bhatia, Vikram ; Bhullar, Rajinder P ; Esmati, Laya
Quinine, a bitter compound, can act as an agonist to activate the family of bitter taste G protein-coupled receptor family of proteins. Previous work from our laboratory has demonstrated that quinine causes activation of RalA, a Ras p21-related small G protein. Ral proteins can be activated directly or indirectly through an alternative pathway that requires Ras p21 activation resulting in the recruitment of RalGDS, a guanine nucleotide exchange factor for Ral. Using normal mammary epithelial (MCF-10A) and non-invasive mammary epithelial (MCF-7) cell lines, we investigated the effect of quinine in regulating Ras p21 and RalA activity. Results showed that in the presence of quinine, Ras p21 is activated in both MCF-10A and MCF-7 cells; however, RalA was inhibited in MCF-10A cells, and no effect was observed in the case of MCF-7 cells. MAP kinase, a downstream effector for Ras p21, was activated in both MCF-10A and MCF-7 cells. Western blot analysis confirmed the expression of RalGDS in MCF-10A cells and MCF-7 cells. The expression of RalGDS was higher in MCF-10A cells in comparison to the MCF-7 cells. Although RalGDS was detected in MCF-10A and MCF-7 cells, it did not result in RalA activation upon Ras p21 activation with quinine suggesting that the Ras p21-RalGDS-RalA pathway is not active in the MCF-10A cells. The inhibition of RalA activity in MCF-10A cells due to quinine could be as a result of a direct effect of this bitter compound on RalA. Protein modeling and ligand docking analysis demonstrated that quinine can interact with RalA through the R79 amino acid, which is located in the switch II region loop of the RalA protein. It is possible that quinine causes a conformational change that results in the inhibition of RalA activation even though RalGDS is present in the cell. More studies are needed to elucidate the mechanism(s) that regulate Ral activity in mammary epithelial cells.
5
项与 盐酸奎宁水合物 相关的新闻（医药）2023-07-10
Research reveals how millions of years of evolution has engineered honey bees to make fast decisions and reduce risk.
Honey bees have to balance effort, risk and reward, making rapid and accurate assessments of which flowers are mostly likely to offer food for their hive. Research published in the journal eLife today reveals how millions of years of evolution has engineered honey bees to make fast decisions and reduce risk.
The study enhances our understanding of insect brains, how our own brains evolved, and how to design better robots.
The paper presents a model of decision-making in bees and outlines the paths in their brains that enable fast decision-making. The study was led by Professor Andrew Barron from Macquarie University in Sydney, and Dr HaDi MaBouDi, Neville Dearden and Professor James Marshall from the University of Sheffield.
"Decision-making is at the core of cognition," says Professor Barron. "It's the result of an evaluation of possible outcomes, and animal lives are full of decisions. A honey bee has a brain smaller than a sesame seed. And yet she can make decisions faster and more accurately than we can. A robot programmed to do a bee's job would need the back up of a supercomputer.
"Today's autonomous robots largely work with the support of remote computing," Professor Barron continues. "Drones are relatively brainless, they have to be in wireless communication with a data centre. This technology path will never allow a drone to truly explore Mars solo -- NASA's amazing rovers on Mars have travelled about 75 kilometres in years of exploration."
Bees need to work quickly and efficiently, finding nectar and returning it to the hive, while avoiding predators. They need to make decisions. Which flower will have nectar? While they're flying, they're only prone to aerial attack. When they land to feed, they're vulnerable to spiders and other predators, some of which use camouflage to look like flowers.
"We trained 20 bees to recognise five different coloured 'flower disks'. Blue flowers always had sugar syrup," says Dr MaBouDi. "Green flowers always had quinine [tonic water] with a bitter taste for bees. Other colours sometimes had glucose."
"Then we introduced each bee to a 'garden' where the 'flowers' just had distilled water. We filmed each bee then watched more than 40 hours of video, tracking the path of the bees and timing how long it took them to make a decision.
"If the bees were confident that a flower would have food, then they quickly decided to land on it taking an average of 0.6 seconds)," says Dr MaBouDi. "If they were confident that a flower would not have food, they made a decision just as quickly."
If they were unsure, then they took much more time -- on average 1.4 seconds -- and the time reflected the probability that a flower had food.
The team then built a computer model from first principles aiming to replicate the bees' decision-making process. They found the structure of their computer model looked very similar to the physical layout of a bee brain.
"Our study has demonstrated complex autonomous decision-making with minimal neural circuitry," says Professor Marshall. "Now we know how bees make such smart decisions, we are studying how they are so fast at gathering and sampling information. We think bees are using their flight movements to enhance their visual system to make them better at detecting the best flowers."
AI researchers can learn much from insects and other 'simple' animals. Millions of years of evolution has led to incredibly efficient brains with very low power requirements. The future of AI in industry will be inspired by biology, says Professor Marshall, who co-founded Opteran, a company that reverse-engineers insect brain algorithms to enable machines to move autonomously, like nature.
2023-04-26
SHANGHAI, April 26, 2023 /PRNewswire/ -- On April 25, 2023, World Health Organization (WHO) gave as the theme for World Malaria Day 2023 Time to deliver zero malaria: invest, innovate, implement. Within this theme, WHO will mainly focus on the third "i" – implement – and notably the critical importance of reaching hard to reach populations with the tools and strategies that are available today.
This year 2023 also marks the 10th anniversary of the Belt and Road Initiative. Medicine knows no borders. Artemisinin and its derivatives have moved from the countries along the Belt and Road to the forefront of the world's battle against malaria since it was discovered by Chinese scientists, more than 50 years ago. Through continuous innovation and global operation, Fosun Pharma has implemented and extended its efforts to "Helping Africa Fight Malaria" and contributed to the implementation of the "Belt and Road Initiative" building a community with a shared positive future for mankind. By the end of 2022, Artesun (Artesunate for Injection), independently developed and manufactured by Fosun Pharma, had treated over 56 million patients with severe malaria worldwide, becoming a prime example for innovative medicinal products developed in China serving the world.
Chinese wisdom and solutions contribute to the global anti-malarial fight and to build a better future through the "Belt and Road Initiative"
As one of the oldest and most widely spreading infectious diseases in the world, malaria continues to have a devastating impact on human health around the world. Historically, malaria was also widespread in China. In the 1970s, a profound effort by researchers in China as a potent antimalarial drug, inspired by ancient traditional Chinese medicine books. Subsequent development, clinical trials and deployment of this new class of drugs was essential for, malaria prevention and control in China, accumulating after more than 70 years of unremitting efforts, certification by the WHO of "Malaria-free" in 2021. From 30 million cases of the disease annually to zero, China's tireless effort to achieve this important milestone in the fight against malaria demonstrates the persistence, efforts and dedication of the Chinese people of several generations of Chinese people.
However, the global efforts to control and eliminate malaria remain challenging: whereas some countries have importantly reduced their malaria burden or even eliminated malaria; others countries have seen an increase in the number of malaria patients. There were an estimated 619,000 deaths due to malaria in 2021 according to the World Malaria Report 2022 released in December 2022. The WHO African Region carries a disproportionately high share of the global malaria burden. In 2021, the Region was home to 95% of malaria cases (234 million) and 96% of malaria deaths (593,000). Children under five years old accounted for about 80% of all malaria deaths in the Region.
To truly win the fight against malaria, malaria must be eradicated globally!
Over the past decade of the Belt and Road Initiative, China's products for malaria prevention and control, as well as China's approach to malaria elimination, have been closely observed and are widely recognized by the WHO and the international malaria community. China's experience continues to contribute to malaria control and elimination in developing countries. The story of China's participation in global malaria elimination extends the purpose of the Silk Road and it aims to create a better future through the "Belt and Road Initiative". From the discovery of artemisinin by Tu Youyou to the wide application of artesunate for injection, an innovative drug developed in China, Chinese wisdom, and approaches contribute to the global fight against malaria.
Fosun Pharma continues its independent R&D of innovative antimalarial drugs used for malaria prevention, treatment of uncomplicated malaria and life-saving treatment of severe malaria patients
In 1987, Guilin Pharma, a Fosun Pharma subsidiary, was authorized the China No. X-01 Class I New Drug Certificate by the Ministry of Health of the PRC for its independently researched and developed artesunate, and the No. X-02 New Drug Certificate for artesunate for injection. Since then, artesunate has been widely used for the treatment of malaria globally, saving countless lives of malaria patients. In 2000, it was listed as one of the essential antimalarial drugs by the World Health Organization. In early 2011, the World Health Organization revised the Guidelines for the Treatment of Malaria by changing the first-line drug for treating severe malaria from quinine to injectable artesunate. By the end of 2022, Fosun Pharma had supplied more than 280 million doses of Artesun (artesunate for injection) to the world, treating more than 56 million severe malaria patients worldwide.
Fosun Pharma continues its independent R&D of innovative antimalarial drugs used for malaria prevention, malaria treatment and life-saving treatment of severe malaria patients. Ranging from malaria treatment to prevention, Fosun Pharma continues to provide solutions, in particular also for children, helping to effectively reduce the malaria burden and death toll of malaria in children under five years old in Africa.
In August 2018, Fosun Pharma's SPAQ-CO® Disp (co-packed sulfadoxine-pyrimethamine dispersible tablets and amodiaquine dispersible tablets), for the prevention of malaria in children, was pre-qualified by WHO (WHO-PQ). By the end of 2022, around 210 million children in Africa have benefited from the "Seasonal Malaria Chemoprevention Program", for which SPAQ-CO® Disp is used as the core drug and which has effectively reduced the morbidity of malaria in children under five years old in Africa.
Continuously improve global operation capability and fulfill corporate social responsibility
Since 2006, Fosun Pharma has actively participated in the Chinese government's Assistance to Africa in Fighting Malaria and has also participated in various public welfare activities and international malaria research projects aiming to help improve malaria control capacity in Africa. Fosun Pharma has been a core supplier of antimalarial drugs to the Global Fund, UNICEF, WHO, and national drug procurement centers in Africa.
In recent years, Fosun Pharma has continuously improved its global operating capacity. By the end of 2022, a revenue of RMB 13.938 billion was earned in regions outside Chinese Mainland and other countries, accounting for 31.7% of its total revenue 2022.
After more than 15 years of operations in Africa, Fosun Pharma has established a sales and marketing network in 39 countries and regions in Africa, ensuring the continued availability of medicines and healthcare products in Africa, including antimalarial drugs. Moreover, Fosun Pharma has set up five regional distribution centers in emerging markets such as Africa, with a first-line commercialization team of approximately 800 people. Among them, the Côte d'Ivoire distribution center in West Africa was officially opened in 2021 and is currently the largest local drug distribution center in the francophone region of West Africa.
In November 2022, Fosun Pharma's Côte d'Ivoire campus project was officially launched, marking an important step for Fosun Pharma in the realization of local drug manufacturing and supply in Africa. In the future, the antimalarials and antibiotics produced by Fosun Pharma's Côte d'Ivoire factory will be distributed through its holding subsidiary Tridem Pharma to help Côte d'Ivoire and other regions in West Africa realize the local supply of essential drugs, thus reducing the risk of drug shortage, important for instance in case of public health crises requiring an emergency response.
Wen Deyong, CEO of Fosun Pharma, said, "As a global innovation-driven pharmaceutical and healthcare industry group, Fosun Pharma always regards innovation as the most important social responsibility for a pharmaceutical enterprise. Up to now, Fosun Pharma has 30 antimalarial drugs prequalified by WHO, ranking first in the world. Meanwhile, Fosun Pharma's global operational networks will further improve the availability and affordability of antimalarial medicines so as to contribute to the achievement of the goal to end malaria by 2030."
About Fosun Pharma
Founded in 1994, Shanghai Fosun Pharmaceutical (Group) Co., Ltd.* ("Fosun Pharma"; stock code: 600196. SH, 02196. HK) is a global innovation-driven pharmaceutical and healthcare industry group. Fosun Pharma directly operates businesses including pharmaceuticals, medical devices, medical diagnosis, and healthcare services. As a shareholder of Sinopharm Co., Ltd., Fosun Pharma expands its areas in the pharmaceutical distribution and retail business.
Fosun Pharma is patient-centered and clinical needs-oriented. The company continuously enriches its innovative product pipeline through independent research and development, cooperative development, license-in, and in-depth incubation. Fosun Pharma improves the research and clinical development capabilities of FIC (First-in-class) and BIC (Best-in-class) new drugs as well as accelerates the R&D and launch of innovative technologies and products.
Guided by the 4IN strategy (Innovation, Internationalization, Intelligentization, and Integration), Fosun Pharma will uphold the development model of "Innovation Transformation, Integrated Operation and Steady Growth", with the mission of creating shareholder values through strengthening its independent R&D and external cooperation and enriching its product pipelines, as well as promoting the global networks and enhancing operational efficiency. Fosun Pharma will actively promote the digital and physical business layout in the pharmaceutical and healthcare industry and is committed to becoming a first-class enterprise in the global medical and health market.
For more information, please visit our official website:
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Company Codes: HongKong:2196, Shanghai:600196
上市批准
2022-11-16
关注并星标CPHI制药在线 盐酸维拉唑酮（vilazodone hydrochloride）是Trovis制药公司开发的一款选择性、可口服的5-羟色胺再摄取抑制剂和部分5-HT1A受体激动剂（双重机制）。其抗抑郁作用主要来自于对5-羟色胺转运体的抑制作用，而它内在的5-HT1A受体部分激动作用，使其在理论上可对抗SSRI（五羟色胺再摄取抑制剂）类药物开始使用时的5-羟色胺水平的短暂下降，加快起效时间。美国食品和药品管理局（FDA）2011年1月批准该药物用于重度抑郁症的治疗。随着市场需求不断扩大，研发人员一直在致力于该药物分子的合成工艺改进。 图1 盐酸维拉唑酮（vilazodone hydrochloride）合成策略 如图1所示，盐酸维拉唑酮（vilazodone hydrochloride）的目前文献报道主要有两种策略，即通过Friedel-Crafts酰基化或者Fischer吲哚合成。Friedel-Crafts酰基化策略使用保护的或无保护的5-氰基吲哚1和4-氯丁酰氯2发生酰化反应得到I，然后5-（哌嗪-1-烷基）苯并呋喃-2-羧酸衍生物II与化合物I反应得到活性药物成分（API）维拉唑酮。Fischer吲哚合成则是以4-氰苯基盐酸肼3为原料，和6-羟基己醛4反应得到化合物I，该策略使用的6-羟基己糖4制备条件非常苛刻，原料3及其衍生物也存在潜在遗传毒 性，所以该策略不适合于放大规模制备产品。 图2 Friedel-Crafts酰基化策略代表性工艺路线 图2展示了维拉唑酮（vilazodone hydrochloride）的Friedel-Crafts酰基化合成策略代表性工艺路线。主要包括Friedel-Crafts酰基化（B）、还原反应（C）、取代反应（D）、水解反应（E）和酰胺化反应（F）5个转化步骤。但该工艺策略存在两个低产率的步骤：Red-Al还原酮（产率26%）；和在碳酸钾、三甲胺条件下的哌嗪片段7·HCl亲核取代反应（产率32%）。经过后续酯水解、酰胺化后，维拉唑酮的总收率仅为3.5%（由7·HCl计算），并且在制备过程中会有多种杂质生成。为此，近期有研究人员对该工艺进行了近一步优化。 图3 盐酸维拉唑酮（vilazodone hydrochloride）制备新工艺 盐酸维拉唑酮（vilazodone hydrochloride）新型制备工艺如图3所示，该工艺从哌嗪片段7·HCl出发，首先将酯以高收率（91%）转化为酰胺12，酰胺12与保护吲哚衍生物6a在碱性条件下发生亲核取代反应得到化合物13；然后，在氢氧化钠碱性条件下脱去Ts保护基团，并经过盐酸成盐得到目标产物盐酸维拉唑酮（vilazodone hydrochloride）。 临床研究显示，维拉唑酮口服与安慰剂相比有较好的抗抑郁效果，其具有耐受性好、不良反应轻微的特点，特别是相比于其他五羟色胺再摄取抑制剂，该药物对性功能影响较小甚至有改善作用。通过上述优化工艺，研究人员实现了盐酸维拉唑酮（vilazodone hydrochloride）单次公斤级制备（1.05Kg），总收率达71%（由7·HCl计算），并将杂质控制在了限度范围之内，为满足盐酸维拉唑酮（vilazodone hydrochloride）的市场需求提供了强有力的保障。 参考文献： 1.Development of a Robust and Scalable Process for the Large-Scale Preparation of Vilazodone, Org. Process Res. Dev. 2022, 26, 10, 2855-2863; 2.维拉唑酮在临床的应用状况[J].中国临床药理学杂志,2014,30(09):862-864. -END-· 企业推荐智药研习社近期课程报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~
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100 项与 盐酸奎宁水合物 相关的药物交易
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 疟疾 | 日本 | 1953-12-01 |
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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 |
|---|
N/A | 300 | 餘獵鹹衊鏇糧鹽製鹹簾(願選選鑰範醖積淵鏇艱) = 願選糧獵鏇選簾獵選網 築網襯願廠憲構鬱網網 (齋願簾淵範遞構糧製觸 ) 更多 | - | 2017-12-28 | |||
临床4期 | 304 | 繭鹹範壓築範衊餘淵鑰(簾齋鏇簾齋築餘獵顧構) = 築艱蓋鹽壓鏇糧築窪襯 窪壓繭淵醖夢蓋構願鑰 (憲齋淵構鬱艱築鹽簾淵 ) | 积极 | 2010-11-01 | |||
繭鹹範壓築範衊餘淵鑰(簾齋鏇簾齋築餘獵顧構) = 構簾鹹淵構築夢鑰窪築 窪壓繭淵醖夢蓋構願鑰 (憲齋淵構鬱艱築鹽簾淵 ) |
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