Omega-3-acid ethyl esters(Trygg Pharma AS)

目前已有多个来自海洋的药物成功上市，它们主要应用于抗癌、镇痛、抗病毒等领域。以下是部分已投入临床使用的代表性海洋来源药物： 一、已获批上市的药物 药物名称 (通用名)海洋来源适应症批准情况/状态Cytarabine (阿糖胞苷, Ara-C)海绵 (Cryptotethya crypta)急性白血病 (特别是急性髓系白血病)1969年获批，是最早的海洋药物之一，已成为化疗基石药物。Eribulin (艾日布林, Halaven®)海绵 (Halichondria okadai)转移性乳腺癌、脂肪肉瘤2010年在美国获批，用于治疗已接受过其他化疗的晚期乳腺癌患者。Brentuximab vedotin (Adcetris®)海兔 (Dolabella auricularia) 衍生肽 (MMAE)霍奇金淋巴瘤、系统性间变性大细胞淋巴瘤2011年获批。抗体偶联药物(ADC)，其细胞毒部分MMAE源自海兔毒素。Lurbinectedin (Zepzelca®)海鞘 (Ecteinascidia turbinata)转移性小细胞肺癌2020年在美国加速批准，用于治疗铂类化疗后进展的患者。Trabectedin (Yondelis®)海鞘 (Ecteinascidia turbinata)软组织肉瘤、卵巢癌2007年在欧盟首次获批，2015年在美国获批。Ziconotide (Prialt®)锥形海螺 (Conus magus) 毒液肽慢性严重疼痛 (鞘内给药)2004年获批，是一种非阿片类强效镇痛药，用于对其他治疗无效的患者。Vidarabine (阿糖腺苷, Ara-A)海绵 (Cryptotethya crypta)疱疹病毒性脑炎、带状疱疹早期抗病毒药物，已被更安全的药物取代，但在历史上意义重大。Omega-3脂肪酸乙酯 (Lovaza®等)深海鱼油 (如鲭鱼、金枪鱼)严重高甘油三酯血症多个品牌已广泛应用，用于降低心血管风险。 二、核心作用机制与特点 抗癌药物： Cytarabine/Eribulin：干扰微管动力学，抑制癌细胞分裂。Trabectedin/Lurbinectedin：与DNA小沟结合，干扰转录和DNA修复，对特定肿瘤有效。Brentuximab vedotin：通过抗体精准递送海洋毒素(MMAE)至癌细胞，实现靶向杀伤。 镇痛药物： Ziconotide：选择性阻断N型电压敏感钙通道，直接作用于脊髓，镇痛效果强且无成瘾性，但需鞘内给药。 开发路径： 这些药物大多经历了从天然产物提取 → 结构鉴定 → 化学合成/优化 → 临床开发的漫长过程。例如，Eribulin是天然产物Halichondrin B的简化合成类似物，保留了活性但更易生产。 三、在研管线与未来展望 除了已上市药物，还有大量海洋来源化合物处于临床前或临床试验阶段，针对癌症、阿尔茨海默病、炎症、感染等疾病。海洋生物的化学多样性（如来自珊瑚、苔藓虫、蓝细菌的化合物）仍是新药发现的宝贵资源。 总结来说，海洋药物已从概念走向药房，在肿瘤和疼痛管理等重要治疗领域确立了不可替代的地位。它们证明了海洋生态系统的巨大药用潜力，并持续激励着新药研发。

A new study suggests fish oil may help reduce insulin resistance even in people who aren't obese. In diabetic rats, omega-3 supplementation improved blood sugar levels, cholesterol, and inflammation by shifting immune cells into a more anti-inflammatory mode.Fish oil may have a surprising role in the fight against insulin resistance, especially in a form of type 2 diabetes that is often overlooked. A Brazilian study published in Nutrients found that omega-3 fatty acids from fish oil reduced glucose intolerance and weakened insulin resistance in rats that were not obese but showed a diabetes-like metabolic condition. The work was funded by FAPESP and focused on Goto-Kakizaki rats, a well established animal model used to study non-obese type 2 diabetes. Type 2 diabetes is marked by high blood sugar that occurs when insulin, the hormone that helps move glucose from the blood into cells, does not work effectively. Fish Oil and Insulin Resistance Omega-3 supplements, including fish oil, are often used by people with cardiovascular disease and type 2 diabetes. However, scientists still know much less about how these fatty acids affect insulin resistance when obesity is not involved. That question matters because obesity is one of the strongest risk factors for type 2 diabetes, but it is not the whole story. An estimated 10% to 20% of people with type 2 diabetes worldwide are not obese. For these patients, the biological roots of insulin resistance may differ from the better known obesity-linked pathways. In the study, researchers gave the rats fish oil at a dose of 2 grams per kilogram of body weight (equivalent to 540 mg/g of eicosapentaenoic acid, or EPA, and 100 mg/g of docosahexaenoic acid, or DHA) three times weekly for eight weeks. By the end of the experiment, the treated animals showed lower insulin resistance, better blood sugar control, reduced inflammatory markers, and improvements in several lipid measures, including total cholesterol, LDL ("bad cholesterol") and triglycerides. The results came from preclinical experiments, so they do not prove that fish oil will have the same effects in people. Still, the findings point to inflammation as a powerful target in non-obese diabetes and suggest that omega-3 fatty acids deserve closer study in this group. A Shift in Immune Cells "Our experiments involved Goto-Kakizaki [GK] rats, an animal model for non-obese type 2 diabetes. We found that insulin resistance can be reduced in these animals by modulating the inflammatory response so as to change the pro defense cells [lymphocytes] from a pro-inflammatory state to an anti-inflammatory state. This process parallels the response of obese individuals with insulin resistance to omega-3 fatty acid supplementation," said Rui Curi, Director of Butantan Institute's Education Center, Professor of Interdisciplinary Graduate Studies in Health Sciences at Cruzeiro do Sul University (UNICSUL), and coordinator of the study. Lymphocytes are white blood cells that help direct the adaptive immune response. When their behavior changes, the effects can spread through the immune system and influence other cells involved in inflammation. "In previous studies, we observed alterations in both lymphocytes and macrophages [large white blood cells that often reside in adipose tissue and are part of the innate immune system, engulfing and destroying pathogens] in non-obese rats with insulin resistance. In such cases, these cells produce more pro-inflammatory cytokines, as is central in obese people with diabetes," Curi explained. "The main aim of the study, therefore, was to find out whether supplementation with fish oil [rich in omega-3] could reverse specific alterations in lymphocytes that had been observed in previous research. Our findings increased our knowledge of the link between inflammation and insulin resistance in non-obese animals, confirming that this is a key factor in diabetes even in the absence of obesity," said Renata Gorjão, last author of the article, and Co-Director of UNICSUL's Program of Graduate Studies in Health Sciences. Inflammation Without Obesity The Nutrients study, conducted during the PhD candidacy of Tiago Bertola Lobato, was part of a broader FAPESP-supported project exploring how insulin resistance develops in non-obese animals. Curi noted that obesity is a major diabetes risk factor, but not the only one. In people who develop diabetes without obesity, one leading hypothesis is that genetic factors may play an important role. In another study published in Cells, Curi, Gorjão, and colleagues investigated whether delayed intestinal transit might also contribute to insulin resistance in non-obese individuals. "Most obese people have chronic low-level inflammation, which is known to affect the insulin signaling pathways. Adipose tissue, which is augmented in obesity, releases pro-inflammatory cytokines that affect the insulin signaling pathways, promoting insulin resistance. In the non-obese model, this impactful characteristic of adipose tissue is absent, but systemic inflammation is present," Curi said. The group had previously shown systemic inflammation in non-obese GK rats with insulin resistance in a study published in the International Journal of Molecular Sciences. Another paper from the same project reported that anti-inflammatory defenses appear to break down early in non-obese GK rats with insulin resistance. Lymph nodes (part of the immune system) from newly weaned 21-day-old GK pups already showed reduced markers of regulatory T-cells (Tregs, cells with anti-inflammatory characteristics). The researchers also detected other early inflammatory changes. That work was published in FEBS Letters, a journal of the Federation of European Biochemical Societies. How Omega-3s May Help The Nutrients study suggests that fish oil may work by moving immune activity away from a damaging inflammatory pattern and toward a more protective one. "Fish oil supplementation reversed this pro-inflammatory profile, displaying a significant anti-inflammatory effect and reducing polarization of Th1 and Th17 cells [lymphocyte subtypes that perform crucial functions in inflammation], followed by a rise in the percentage of Tregs, which can inhibit the activation of pro-inflammatory lymphocytes. Thus the action of omega-3 fatty acids on lymphocytes, modulating them from a pro-inflammatory state to an anti-inflammatory state, may have triggered the reduction in insulin resistance in these animals," Lobato said. That immune shift is important because insulin resistance is not only a problem of sugar metabolism. It is also deeply connected to inflammation. When inflammatory signals remain elevated, they can interfere with insulin signaling and make it harder for cells to respond to the hormone. The study adds to a growing view of type 2 diabetes as a disease shaped by both metabolism and the immune system. In this case, fish oil appeared to improve blood sugar regulation not simply by changing fat levels, but by changing the inflammatory environment that helps drive insulin resistance. What Later Studies Add Since the Nutrients paper was published, related human research has continued to examine how omega-3 fatty acids may influence early diabetes risk and metabolic health. A 2025 double blind randomized controlled trial in Food and Function tested fish oil supplementation in healthy middle aged and older adults. Over 12 weeks, the fish oil groups had dose related increases in serum EPA and DHA. The researchers also reported decreases in fasting insulin and the HOMA-IR index, a common marker of insulin resistance. Fasting blood glucose trended downward across groups, and several lipid related measures also improved. Another 2024 analysis in Nutrition and Diabetes used modeling data from 161 patients with type 2 diabetes to explore the relationship between omega-3 levels and HbA1c, a longer term marker of blood sugar control. The authors reported a dose related association and proposed that omega-3 intake could be studied in a more individualized way, while also noting that the role of omega-3s in type 2 diabetes remains debated. Together, these studies do not settle the question of whether fish oil should be used to manage diabetes. Human evidence remains mixed, and the Brazilian study was conducted in animals, not people. However, the newer findings are consistent with the idea that omega-3 fatty acids may affect insulin resistance and inflammation in ways worth testing more carefully. More Research Still Needed Despite the promising findings, the researchers stressed that the results should be interpreted cautiously. Animal studies are useful for uncovering biological mechanisms, but clinical trials are needed before scientists can know whether the same strategy works in people with non-obese type 2 diabetes. "These studies involved well-established experimental models that mimic insulin resistance in non-obese individuals. Trials in humans are needed to estimate the ideal dose and the most indicated type of omega-3 fatty acid," Curi said. For now, the study offers a compelling clue: in diabetes, body weight may not be the only driver of insulin resistance. Inflammation can play a central role even without obesity, and fish oil may help reveal how that hidden process can be changed.