Amoxicillin Trihydrate

//  •曼迪霉素的潜力不仅符合先声的研发方向，还有望解决临床未满足的迫切需求；•曼迪霉素可以靶向真菌细胞膜上多种磷脂分子；•目前正在开展临床前研究，预计至多1～2年后就可进入人体试验；•先声一直在抗感染领域寻求合作，尤其对有很强科学依据的产品感兴趣。一直在抗感染领域寻求合作的先声药业，终于出手。近期，中国药科大学王宗强教授团队联合山东大学药学院尚卓教授，利用全球先进的合成生物学平台开发的一种新型抗真菌候选药物曼迪霉素（mandimycin），并在Nature发文。此后不久即有消息传来，先声药业正与王宗强团队共同推进这款产品的后续开发。王宗强告诉研发客：“曼迪霉素的亮点在于，它对几乎所有临床真菌及耐药菌均具有良好的杀菌活性，其独特的磷脂分子靶向机制使其耐药率低，不会引起传统靶向麦角甾醇带来的肾毒性。如果开发成功，它有望成为侵袭性真菌治疗的新一道防线。”“曼迪霉素的潜力不仅符合公司研发方向，而且有望解决临床未满足的迫切需求。顺利的话，这将是展现药企与科研院校合作转化的一个很好的案例。当然，我们更希望这个药不单单造福中国人群，也能造福全球患者。”先声药业高级副总裁兼首席医学官（CMO）吴奕涵博士说。拓展阅读  先声的创新面孔：74%占比背后的布局未来十年抗真菌新药稀缺真菌感染已成为日益严重的全球性威胁。美国国立卫生研究院（NIH）数据显示，全世界每年发生的严重真菌感染病例超过1.5亿例，每年造成约170万人死亡，并且这些数字还在不断上升。然而，开发针对真菌感染的新型疗法并不容易。根据WHO抗真菌药物报告，过去十年，仅有4种新型抗真菌药获得美国、欧盟或中国监管部门批准。针对WHO重点真菌病原体清单（FPPL）所列最具健康威胁的真菌，目前全球只有9种产品处于临床阶段，其中仅3种进入3期临床，另有22种药物处于临床前开发阶段。这也意味着，未来十年内预计获批的新药寥寥无几。表格来源 ｜ WHO抗真菌药物报告“当下，全球布局抗真菌感染新药的公司并不多，主要原因在于投资回报率低。通常情况下这类药物治疗周期大约在数周到数个月，但治疗成本不高，且每一款药物面向的患者群不大，而研发一款新药的投入却不比其他疾病领域的产品低。”吴奕涵说。他进一步表示，科学界发现和记录的真菌种类高达数万种，而一款抗菌药很难对抗所有真菌，耐药和突变的发生更是给药物开发带来极大挑战。临床研究入组方面的难点也很明显，尤其是一些严重感染、罕见真菌感染的患者，通常需要较长时间才能招募到足够的受试者。目前临床上应用广泛的抗真菌药物主要有唑类、多烯类、氟胞嘧啶类及棘白菌素类这四大类。不过WHO报告也指出了现有抗真菌疗法的不足，比如严重副作用、频繁出现药物相互作用、剂型有限、需长期住院等问题。曼迪霉素是王宗强团队从超31.6万种细菌基因组中筛选基因簇后发现的一种多烯类天然产物。与传统多烯类抗真菌药物大多靶向细胞膜上的麦角固醇不同，曼迪霉素可以靶向真菌细胞膜上多种磷脂分子。这种多重靶向结合能力赋予了其强效且广谱的杀菌特性，对WHO FPPL中19种真菌几乎都有效，并显著降低耐药突变体产生的可能性。一系列毒理测试还发现，曼迪霉素在肾毒性和溶血性方面远低于两性霉素B，而水溶性较两性霉素B提升9700倍以上。这也意味着，无论是口服还是静脉注射，它都能在治疗中快速起效，同时具有很好的安全性。一两年后进入临床此次Nature的重磅发文将曼迪霉素推向公众视野，不过在此之前，先声早已看准这一产品。据吴奕涵介绍，近年来，国家一直在鼓励药企与高校、科研院所合作，以促进科研成果转化。对此，先声积极响应，并与包括中国药科大学在内多家高校建立交流。“药企不能闭门造车，应深化与科研院校协同创新。”他指出，在研发资源有限的情况下，仅凭企业自身力量难以全面追踪前沿突破，而产学研合作既能弥补科研视野的局限性，又能为药物研发开辟新路径、捕捉创新机遇。2024年年中，中国药科大学向先声推荐了王宗强团队及其科研成果。在交流过程中，先声被曼迪霉素的广谱抗真菌特性所吸引，尤其是对耐药真菌的显著疗效。为了加快推动该分子的开发，先声为其提供了一定资金支持。随着更多研究数据的出炉，也进一步坚定了先声合作开发该产品的决心。近水楼台先得月，同样在南京的先声与王宗强团队达成合作也显得顺理成章。王宗强表示：“创新药物的研究过程充满各种不可预知的问题，选择先声主要是看重他们的创新和研发实力，希望通过合作加快产品上市进度。”目前，曼迪霉素已完成早期发现研究。接下来，双方将利用各自的专长，进一步推动其在CMC、药效学、药代动力学、毒理学等方面的临床前研究和开发工作，并基于整个数据包向药监局递交IND。“我们预计，至多1～2年后就可以进入人体临床试验，首个适应症可能是一些严重、致死性的真菌感染。”吴奕涵说。拓展阅读  先声安进合作意义在哪里？先声的抗感染布局思路事实上，这并非先声首次布局抗感染领域。早在30年前，先声成立之初就凭抗感染起家，先后开发出十多种仿制药用以治疗细菌或病毒引起的感染性疾病，包括安信（注射用比阿培南）、再林（阿莫西林颗粒/分散片/胶囊）、再立克（阿比多尔分散片）等。其中，再林还是中国首家上市的阿莫西林类儿童专用口服抗生素，开创了此类药物的免皮试时代。在做出全面转型创新的决定后，先声于2018年在上海建设第一个创新中心，并重点围绕感染在内多个疾病领域开展新药研发工作。5年后，由先声合作研发的国产3CL抗新冠创新药先诺欣在中国获得附条件批准上市。次年，先诺欣还成为国内首款获得常规批准的口服抗新冠病毒药物。这也标志着先声在抗感染领域从仿制向创新迈出重要一步。此外，先声与安帝康合作开发的抗流感1类创新药玛氘诺沙韦也于近期在中国申报上市并获得药监局受理。这是一款cap依赖型核酸内切酶抑制剂，全病程仅需口服一粒，即可在24小时内阻止流感病毒复制。此次引入曼迪霉素，无疑是先声在抗感染布局上落下的重要一子。吴奕涵表示：“抗感染领域有着极大未满足临床需求，开发能够应对真菌感染和抗真菌耐药的产品是一件非常有意义的工作。我们相信，只要能研发出一款真正的好药，回报自会随之而来。尤其在竞争较少的时候，选择一个偏冷门的赛道或疾病领域是一个不错的选择。”正是如此，先声一直在抗感染领域寻求合作，目光也不局限于某个特定靶点或适应症。吴奕涵表示，只要是有很强的科学依据，能够满足临床迫切的需求，先声都有兴趣。编辑 | 姚嘉yao.jia@PharmaDJ.com 总第2448期访问研发客网站，深度报道和每日新闻抢鲜看www.PharmaDJ.com

Delivery Method: VIA EMAIL WITH READ RECEIPT Product: Animal & Veterinary Drugs Recipient: Recipient Name Cameron Muir FishMoxFishFlex/Simple Pet Health LLC 520 South 850 East, Ste A1 Lehi , UT 84043 United States info@fishmoxfishflex.com Issuing Office: Center for Veterinary Medicine United States WARNING LETTER May 8, 2025 Re: 707196 Dear Cameron Muir: This letter concerns your firm's distribution of animal drug products for use in aquarium fish and birds. In April 2025, the U.S. Food and Drug Administration (FDA) reviewed your website (https://fishmoxfishflex.com/), where you take orders for Fish Mox and Fish Mox Forte Amoxicillin, Bird Zithro Azithromycin, Fish Flex Cephalexin and Fish Flex Forte Cephalexin, Fish Flox Forte Ciprofloxacin, Fish Cin Clindamycin, Fish Doxy Doxycycline, Fish Zole Metronidazole and Fish Zole Forte Metronidazole, Fish Pen Forte Penicillin, and Fish Sulfa Forte Sulfamethoxazole /Trimethoprim. The claims on your website establish that these products are intended for use in the cure, mitigation, treatment, or prevention of diseases in animals, which makes them drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) [21 U.S.C. § 321(g)(1)(B)]. In addition, these animal drugs are misbranded under section 502(o) of the FD&C Act [21 U.S.C. § 352(o)] because they have not been drug listed with FDA, nor have they been manufactured in a facility that is registered with FDA in accordance with sections 510(b) and (j) of the FD&C Act [21 U.S.C. § 360(b), (j)]. As discussed below, introducing or delivering these unapproved and misbranded new animal drugs for introduction into interstate commerce violates section 301(a) of the FD&C Act [21 U.S.C. § 331(a)]. UNAPPROVED NEW ANIMAL DRUGS Examples of claims observed on your website (https://fishmoxfishflex.com/) that establish the intended use of these products as drugs include, but may not be limited to, the following: Fish • Simple Pet Health Fish Mox and Simple Pet Health Fish Mox Forte (Amoxicillin), 250 mg and 500 mg capsules. According to your website an “Antibacterial Fish Medication,” this product “is a broad-spectrum antibiotic that controls gram-positive and some gram-negative bacteria in fish. It works by halting the multiplication of bacteria associated with both fresh and salt water ornamental fish diseases. This fish antibiotic is useful for control of some common bacterial diseases in fish including Dropsy, Fin Rot, Red Pest, and disease caused by bacteria such as Aeromonas, Pseudomonas, and Mycobacterial (Gill diseases and Chondrococcus).” • Simple Pet Health Fish Flex and Simple Pet Health Fish Flex Forte (Cephalexin), 250 mg and 500 mg capsules. According to your website an “Antibacterial Fish Medication,” this product “is a broad-spectrum antibiotic that is used in treating a wide variety of non-specific bacterial infections during the most active and multiplying stages of infection. This effective fish antibiotic is helpful with treating a number of pathogenic bacteria associated with ornamental fish diseases.” • Simple Pet Health Fish Flox Forte (Ciprofloxacin), 500 mg tablets. According to your website an “Antibacterial Fish Medication,” “You can help your finned friends feel better and watch your aquarium thrive again with Ciprofloxacin Tablets. This synthetic, board spectrum medication is used treat different strains of bacteria that can plague your fish.” • Simple Pet Health Fish Cin (Clindamycin), 150 mg tablets. According to your website an “Antibacterial Fish Medication,” this product “is an antibiotic that exerts a bactericidal action on gram-positive and some gram-negative bacteria in fish. Used for the control of some common bacterial fish diseases, such as Aeromonas, Pseudomonas, and Mycobacterial (Gill diseases and Chondrococcus).” • Simple Pet Health Fish Doxy (Doxycycline Hyclate), 100 mg capsules. According to your website an “Antibacterial Fish Medication,” this product “is an antibiotic that exerts a bactericidal action on gram-positive and some gram-negative bacteria in fish. Used for the control of some common bacterial fish diseases such as Tail Rot, Mouth Rot, Fin Rot, and Septicemia.” • Simple Pet Health Fish Zole and Simple Pet Health Fish Zole Forte (Metronidazole), 250 mg and 500 mg tablets. According to your website an “Antibacterial Fish Medication,” this product “is an antibiotic that exerts a bactericidal action on gram-positive and some gram-negative bacteria in fish. Useful to help control some common bacterial diseases in fish such as Aeromonas, Pseudomonas, and Mycobacterial (Gill diseases and Chondrococcus). Effective against anaerobic bacteria, a bacteria that only grows where there is no oxygen. Also used to control parasitic diseases such as Cryptocaryon irritans, Ichthyophthirius multifiliis, and Hexamita.” • Simple Pet Health Fish Pen Forte (Penicillin), 500 mg tablets. According to your website an “Antibacterial Fish Medication,” this product “is an antibiotic that exerts a bactericidal action on gram-positive and some gram-negative bacteria in fish. Used in the control of some common bacterial diseases in fish, including diseases caused by bacteria such as fin and tail rot and Flexibacteria infections.” • Simple Pet Health Fish Sulfa Forte (Sulfamethoxazole/Trimethoprim), 800/160 mg tablets. According to your website an “Antibacterial Fish Medication,” this product “is an antibiotic that exerts a bactericidal action on gram-positive and some gram-negative bacteria in fish. Used in the control of some common bacterial diseases in fish, such as Aeromonas, Pseudomonas, and Mycobacterial (Gill diseases and Chondrococcus).” Birds • Simple Pet Health Bird Zithro (Azithromycin), 250 mg tablets. According to your website an “Antibacterial Bird Medication,” this product “is a fish antibiotic that is used for systemic and local infections in pigeons, pet birds, and exotic birds. This antibiotic is effective against gram-positive bacteria, as well as some gram-negative bacteria, spirochetes, anaerobic bacteria, and other types of microorganisms. Bird ZithroTM is also effective against Chlamydia psittaci in cockatiels. The active ingredient in this medication works by inhibiting the growth of bacteria, which helps to eliminate the bacteria and the infection.” These products are new animal drugs under section 201(v) of the FD&C Act [21 U.S.C. § 321(v)] because they are for use in nonfood-producing fish and birds, which are minor species as defined by sections 201(nn) and (oo) of the FD&C Act [21 U.S.C. § 321(nn) and (oo)], and are not the subject of a final FDA regulation finding either that the drugs are generally recognized among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the drug’s labeling, or finding that the exception to the criterion in section 201(v)(1) of the FD&C Act has been met. To be legally marketed, a new animal drug must be the subject of an approved new animal drug application, a conditionally approved new animal drug application, or a listing on the Index of Legally Marketed Unapproved New Animal Drugs for Minor Species (“index listing”) under section 512, 571, or 572 of the FD&C Act [21 U.S.C. § 360b, 360ccc, and 360ccc-1]. The FDA approval and index listing processes allow FDA to ensure that there is adequate evidence to demonstrate that new animal drugs are safe, properly manufactured, accurately labeled, and meet the relevant effectiveness standard. The animal drugs named above have not been approved, conditionally approved, or index listed. Animal drugs that lack the required approval or index listing are considered unsafe and adulterated under sections 512(a) and 501(a)(5) of the FD&C Act [21 U.S.C. §§ 360b(a) and 351(a)(5)]. Introduction or delivery for introduction of an adulterated animal drug into interstate commerce is prohibited under section 301(a) of the FD&C Act [21 U.S.C. § 331(a)]. The FDA is particularly concerned about the marketing of these unapproved animal drugs because they contain antimicrobials considered medically important to human health. The growing threat of antimicrobial resistance, especially to drugs that are medically important in human medicine, has prompted FDA to promote judicious use of these drugs in animals. A key part of this effort is ensuring that these medically important antimicrobials are used only under the supervision of a licensed veterinarian. Over-the-counter use of these drugs without veterinary oversight contributes to the development of antimicrobial resistance, posing risks to both human and animal health. MISBRANDED NEW ANIMAL DRUGS Sections 510(b)(1) and (j)(1) of the FD&C Act [21 U.S.C. § 360(b), (j)] require that manufacturers (which includes repackers and relabelers) of drugs, including animal drugs, register their manufacturing establishments with FDA and provide the agency with a list of all the drug products they manufacture. Drugs that are manufactured in unregistered establishments or that have not been listed with FDA are misbranded under section 502(o) of the FD&C Act. None of the animal drugs in this letter are drug listed with FDA, nor have they been manufactured in a facility that is registered with FDA. Accordingly, these animal drugs are misbranded. Introduction or delivery for introduction of a misbranded animal drug into interstate commerce is prohibited under section 301(a) of the FD&C Act. This letter is not intended to be an all-inclusive statement of violations that may exist in connection with your product(s). You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law and FDA regulations. This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may lead to legal or regulatory action, including without limitation, seizure and injunction. You should be aware that if we take enforcement action against any of the drugs named above or other unapproved/unindexed products you market that contain medically important antimicrobials, we may take action against all of your products that violate the FD&C Act at the same time, including but not limited to enjoining the manufacturing and distribution of all of your unapproved/unindexed products. We have the following comments: 1. You can legally market the products named above if you obtain an index listing, approval, or conditional approval. Information about the processes and requirements for obtaining an index listing and various types of animal drug approval is available on the FDA website at • https://www.fda.gov/animal-veterinary/development-approval-process/minor-useminor-species and • https://www.fda.gov/animal-veterinary/development-approval-process/new-animal-drug-applications The index listing process was added to the FD&C Act in 2004 as a streamlined alternative process that addresses the challenges of obtaining FDA approval for drugs for minor species (which are any animal species other than horses, cattle, pigs, dogs, cats, chickens, and turkeys). Drugs intended for use in minor species not used for human or animal food are eligible for index listing. Because the above-named products are intended for use in nonfood-producing fish and birds, you may wish to explore the index listing process. The approval process can also be used for drugs for use in these species. 2. Information on establishment registration and drug listing is available on the FDA website at: • https://www.fda.gov/industry/fda-basics-industry/registration-and-listing Within fifteen (15) working days of receiving this letter, please notify this office in writing of the specific steps that you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective actions within fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration. Your written response should be sent to Dr. Vic Boddie, United States Food and Drug Administration, Center for Veterinary Medicine, Office of Surveillance and Compliance, Division of Drug Compliance, by emailing CVMUnapprovedDrugs@fda.hhs.gov. Sincerely, /S/ Cindy L. Burnsteel, DVM Acting Director, Division of Drug Compliance Office of Surveillance and Compliance Center for Veterinary Medicine Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.