Celecoxib

痛经是困扰全球女性的常见健康问题，其影响远不止短暂的生理不适。据统计，约50%至90%的育龄女性曾经历不同程度的经期疼痛，其中10%至15%的女性会因痛经而严重影响工作、学习与日常生活。 痛经主要分为两类：原发性痛经指无盆腔器质性病变的周期性经期疼痛，多见于青春期女性；继发性痛经则由盆腔疾病引发，例如子宫内膜异位症、子宫腺肌病等，疼痛往往随年龄增长而加剧。过去几十年来，痛经治疗药物经历了从传统止痛药到激素调节、从中药复方到靶向治疗的显著演进，形成了多层次的现代药物体系。 一、痛经认知与治疗原则的演进 对痛经的科学认知始于20世纪初。1937年，医学界首次提出“抑制排卵可缓解痛经”的理论，为后续药物治疗奠定了重要基础。1960年代，随着对前列腺素研究的深入，科学家发现痛经与子宫内膜前列腺素，尤其是PGF2α的过量合成密切相关。在月经周期中，随着孕激素水平下降，磷脂酶A2被激活，促使花生四烯酸转化为前列腺素。过高的前列腺素会引起子宫平滑肌过度收缩、血管痉挛及局部缺血，直接导致下腹绞痛，并可能伴随恶心、头痛等全身症状。这一机制的确立彻底改变了痛经的治疗方向——从单纯的止痛转向针对病因的调节。 在治疗策略上，原发性痛经以缓解症状和抑制前列腺素合成为目标；而继发性痛经则需优先处理原发疾病。临床医生强调，若患者出现疼痛进行性加重、经期延长或经量异常，特别是伴随不孕史或盆腔检查异常时，必须及时排查器质性病变。这种分类诊疗原则避免了盲目止痛掩盖潜在疾病的危险，也推动了痛经药物研发的精细化发展。 二、现代西药的多方位发展 痛经的药物治疗史是一部从粗放止痛走向精准调控的演变史。在20世纪前，传统医学主要依赖热敷、草药或阿片类药物缓解症状，但效果有限且副作用风险高。1930年代后，随着内分泌学的发展，激素疗法开始萌芽；而1960年代口服避孕药的问世，则标志着一个转折点的到来。 2.1口服避孕药：从避孕到治痛的多效应用 1960年代初，口服避孕药进入临床应用后不久，医生们意外发现许多女性在用药后痛经症状显著改善。这一现象引发了系统的研究，证实复方口服避孕药（含雌激素与孕激素）通过抑制排卵和减少子宫内膜增殖，能有效降低前列腺素和血管加压素的合成与释放，使痛经缓解率达到90%以上。与传统止痛药相比，它不仅针对症状，更从源头调节激素失衡状态，特别适合同时需要避孕或月经量过多的女性。尽管国内曾因观念问题推广受限，但大量循证医学证据已证明其安全性和可逆性——停药后生育能力即可恢复。 现代避孕药治疗痛经一般采用短效剂型，例如炔诺酮、甲地孕酮复方制剂，需连续服用21天，停药后出现撤退性出血。治疗方案推荐从月经周期第5日开始，持续3个月经周期为一疗程。值得注意的是，该疗法存在特定禁忌证：40岁以上吸烟女性、有血栓病史、乳腺癌患者及严重肝功能不全者需避免使用。 2.2前列腺素合成酶抑制剂：痛经治疗的里程碑突破 1970年代，基于对前列腺素机制的深入理解，非甾体抗炎药（NSAIDs）作为前列腺素合成酶抑制剂被引入痛经治疗领域。这类药物通过抑制环氧合酶（COX）活性，阻断花生四烯酸转化为前列腺素，从而降低子宫张力和收缩强度。其优势在于直接针对关键病理环节，且仅在经期使用，不影响整体内分泌平衡。 NSAIDs的使用策略强调“早期足量”原则：在疼痛发作初期，最好在经血出现前或第一时间开始服药，并持续2-3天，覆盖前列腺素分泌高峰期。临床数据显示，规范用药可使60%至90%的患者获得满意缓解。但这类药物也存在不容忽视的副作用风险： 胃肠道反应：前列腺素具有胃黏膜保护作用，而NSAIDs抑制其合成后，可能导致消化不良、胃痛甚至溃疡出血。建议餐后服药，避免咖啡、酒精刺激。 肝肾负担：大剂量或长期使用可能造成转氨酶升高、间质性肾炎，尤其脱水状态下风险增加。 过敏反应：部分哮喘患者可能诱发支气管痉挛，即阿司匹林哮喘。 血液系统影响：抑制血小板聚集功能，延长出血时间。 2.3现代痛经药物体系的扩展与多样化选择 除避孕药和NSAIDs外，痛经药物库在近几十年不断丰富，形成多靶点干预体系： 钙通道阻滞剂：硝苯地平作为代表药物，通过阻断钙离子内流松弛子宫平滑肌，尤其适用于合并高血压的痛经患者。常用方案为5-10mg舌下含服，10-30分钟起效。 β-受体兴奋剂：例如沙丁胺醇（舒喘灵）通过激活β受体提高细胞内环磷酸腺苷（cAMP）水平，减少肌球蛋白轻链激酶活化，从而抑制子宫收缩。但因其可能引起心悸、震颤，临床应用受限。 维生素类辅助治疗：维生素K3以4mg肌注剂量使用，通过调节钙稳态缓解平滑肌痉挛；维生素B6也被证明有助于减轻经前紧张相关的疼痛。 中重度疼痛的二线用药：对NSAIDs反应不佳者，可考虑弱阿片类药物如曲马多，或谨慎使用可待因。但需警惕成瘾风险及便秘等副作用。 继发性痛经的药物选择需以原发病治疗为核心，例如，子宫内膜异位症常用促性腺激素释放激素激动剂（GnRH-a）诱导“人工绝经”；子宫腺肌病可能采用孕激素宫内缓释系统，如曼月乐环。这类治疗需在妇科医生指导下个体化设计。 三、中医中药在痛经治疗中的独特地位与科学价值 传统中医药在痛经治疗领域积累了丰富经验，其核心在于“辨证论治”——针对不同体质和证候施以差异化方案。宋代《太平惠民和剂局方》记载的四物汤（当归、川芎、白芍、熟地黄）被誉为“妇科第一方”，开创了补血调经的先河。现代药理研究表明，其作用机制涵盖多个层面： 双向调节子宫功能：当归所含挥发油和阿魏酸抑制子宫收缩，而其水溶性成分促进子宫组织微循环。 缓解平滑肌痉挛：白芍中的芍药苷具有显著的解痉镇痛作用。 纠正贫血状态：熟地黄多糖刺激造血祖细胞增殖，改善血虚症状。 在四物汤基础上，历代医家发展出多种经典加减方。 中医强调因时用药，经前以理气活血为主，经期侧重温经止痛，经后则重补虚固本。例如，寒凝血瘀者，在经前一周服用温经汤效果较好；气血虚弱者，在经后服用八珍汤效果最佳。这种分阶段治疗模式与现代医学的周期性干预理念不谋而合。 四、未来展望：个体化、精准化及中西医结合的痛经治疗 痛经药物研发正朝着高效低毒和个体化方向迈进。新型COX-2选择性抑制剂，例如塞来昔布，在保留抗炎作用的同时降低胃肠道风险；促性腺激素释放激素拮抗剂，例如Elagolix，为子宫内膜异位症相关疼痛提供了新选择。基因组学研究试图解析痛经的遗传易感性，例如前列腺素受体基因多态性可能影响药物反应，为未来精准用药提供依据。 现代医学正重新审视传统医学的价值，研究表明，四物汤可通过调节NF-κB信号通路抑制炎症因子释放；艾灸关元穴能降低血清PGF2α水平。这种中西医结合的多靶点干预模式可能成为未来研究热点。 痛经管理的另一趋势是从单纯医疗干预转向全程健康管理。建议女性记录月经周期、疼痛程度及用药反应，形成个人健康档案。当疼痛性质改变或出现“危险信号”，例如非经期盆腔痛、性交痛、异常出血时，应及时就诊排查器质性疾病。 回望痛经治疗发展史，从20世纪初的束手无策，到如今拥有激素调节、靶向止痛、微创手术等丰富手段，医学的进步显著提升了女性生活质量。很多人认为痛经是女人总要忍受的痛苦，实际上痛经不需要忍。在科学与人文交融的现代医学理念下，痛经的治疗必将走向更精准、更人性化的新阶段，让每一位女性都能以健康与尊严拥抱生命的周期性律动。 参考来源： [1]Journal of Pain Research. *Electroacupuncture Combined with Parecoxib Regulates Inflammatory Response in Primary Dysmenorrhea via COX-2/NF-κB/NLRP3 Pathway [2]International Journal of Osteopathic Medicine.Potential Effects of Combining Osteopathic Manual Therapy and Menstrual Awareness on Primary Dysmenorrhea: A Randomized Clinical Trial.  [3]网易新闻. 经行腹痛：中医视角下的痛经辨证与身心调摄 药事纵横投稿须知：稿费已上调，欢迎投稿

CAMBRIDGE, Mass., July 31, 2025 /PRNewswire/ -- NeuroSense Therapeutics Ltd. (NASDAQ: NRSN) ("NeuroSense"), a late-stage clinical biotechnology company developing novel treatments for severe neurodegenerative diseases, today provided business update with corporate highlights to date and financial results of the first half of 2025. NeuroSense is advancing PrimeC, its investigational combination therapy for amyotrophic lateral sclerosis (ALS), through regulatory pathways while preparing for a pivotal Phase 3 trial. "The first half of 2025 has been transformational for NeuroSense. We regained compliance with Nasdaq's stockholders' equity requirement, generated additional long–term data from our Phase 2b ALS, PARADIGM study, and advanced our manufacturing capabilities," said Alon Ben–Noon, Chief Executive Officer of NeuroSense. "Our team is focused on accelerating the path to a pivotal Phase 3 trial as the next step in potentially bringing a meaningful treatment to people living with ALS as quickly as possible." Upcoming Corporate Highlights for H2 2025 include: NOC/c Submission in Canada – Following feedback from Health Canada that the Company's initial request did not fulfill the criteria for advanced consideration under the Notice of Compliance with conditions (NOC/c) policy, and in line with Health Canada's suggestion, NeuroSense plans to submit a new request supported by additional data, with the goal of securing an NOC/c for PrimeC. Phase 3 trial commencement – Following positive regulatory feedback from the FDA, NeuroSense plans to begin a multinational Phase 3 study of PrimeC in ALS in the second half of 2025. Advancing binding term sheet with a global pharmaceutical partner – Following the execution of a binding term sheet in the fourth quarter of 2024 to advance the development and commercialization of PrimeC, its proprietary treatment drug for ALS in certain key territories, discussions are continuing and may yield a definitive partnership agreement in the near future. First Half 2025 Corporate Highlights Nasdaq listing compliance restored In January 2025 NeuroSense received formal notice from Nasdaq that it had regained compliance with the stockholders' equity requirement after completing a $5 million private placement in December 2024. The financing strengthened the Company's balance sheet and raised shareholders' equity above Nasdaq's minimum requirement. Additional long –term data from the Phase 2b PARADIGM study In February 2025 NeuroSense reported new analyses from the completed 18–month Phase 2b PARADIGM study in ALS. The new analysis revealed that in the per-protocol population (participants who adhered to the protocol), treatment with PrimeC slowed functional decline by ~40%. Overall survival improved by 74%, complication–free survival improved by 79%, and patients experienced slower decline in slow vital capacity by 26%. These data reinforce the disease–modifying potential of PrimeC and underpin the design of the planned Phase 3 study. Presentation of biomarker and mechanistic data At the Annual Meeting of the American Academy of Neurology (AAN) in April 2025, members of NeuroSense's scientific advisory board presented further analyses from the PARADIGM study. Dr. Jeremy Shefner highlighted safety, efficacy and biomarker data showing that PrimeC has disease–modifying potential and may redefine ALS treatment. Dr. Jeffrey Rosenfeld discussed microRNA modulation and iron–related biomarkers as evidence of multi–target engagement. These findings were later expanded upon in a release describing how PrimeC consistently modulated microRNAs associated with ALS, providing mechanistic insight consistent with observed clinical improvements. Manufacturing scale –up to commercial levels In May 2025 NeuroSense successfully scaled production of PrimeC to a commercial level and selected a global contract development and manufacturing organization (CDMO) to ensure supply chain readiness for potential commercialization. The Company validated the manufacturing process, qualified suppliers, and demonstrated product stability supporting a 36–month shelf–life. H1 2025 Financial Results: Research and development expenses for the six months ended June 30, 2025 and 2024 were $2,503 thousand and $3,733 thousand, respectively. The decrease of $1,230 thousand, or 32.9%, was mainly attributed to the decrease in clinical activity. General and administrative expenses for the six months ended June 30, 2025 and 2024 were $2,189 thousand and $2,291 thousand, respectively. The decrease of $102 thousand, or 4.4%, is considered immaterial. Operating expenses for the six months ended June 30, 2025 and 2024 were $4.7 million and $6 million, respectively due to the reasons described above. A summary of NeuroSense's unaudited consolidated financial results is included in the tables below. About ALS Amyotrophic lateral sclerosis ("ALS") is an incurable neurodegenerative disease that causes complete paralysis and death within 2-5 years from diagnosis. Every year, more than 5,000 people are diagnosed with ALS in the U.S. alone, with an annual disease burden of $1 billion. The number of people living with ALS is expected to grow by 24% by 2040 in the U.S. and EU. About PARADIGM PARADIGM is a prospective, multinational, randomized, double-blind, placebo-controlled Phase 2b (NCT05357950) clinical trial of PrimeC in ALS. The trial included 68 participants living with ALS in Canada, Italy, and Israel. During the first 6 months of the trial, 45 participants were randomized to receive PrimeC, and 23 participants were randomized to receive placebo. This was followed by a 12-month open-label extension with all participants receiving PrimeC in a blinded manner, where neither the participants nor the clinical staff were aware of the initial treatment allocation. Most patients enrolled in both the active and placebo arms of the trial were concurrently treated with Riluzole, the ALS standard of care medication, indicating PrimeC slowed disease progression well beyond the level afforded by the FDA approved ALS drug. About PrimeC PrimeC, NeuroSense's lead drug candidate, is a novel extended-release oral formulation composed of a unique fixed-dose combination of two FDA-approved drugs: ciprofloxacin and celecoxib. PrimeC is designed to synergistically target several key mechanisms of ALS that contribute to motor neuron degeneration, inflammation, iron accumulation and impaired ribonucleic acid ("RNA") regulation to potentially inhibit the progression of ALS. NeuroSense completed a Phase 2a clinical trial which met its safety and efficacy endpoints including reducing functional and respiratory deterioration and statistically significant changes in ALS-related biological markers indicating PrimeC's biological activity. PrimeC was granted Orphan Drug Designation by the U.S. Food and Drug Administration and the European Medicines Agency. About NeuroSense NeuroSense Therapeutics, Ltd. is a clinical-stage biotechnology company focused on discovering and developing treatments for patients suffering from debilitating neurodegenerative diseases. NeuroSense believes that these diseases, which include amyotrophic lateral sclerosis (ALS), Alzheimer's disease and Parkinson's disease, among others, represent one of the most significant unmet medical needs of our time, with limited effective therapeutic options available for patients to date. Due to the complexity of neurodegenerative diseases and based on strong scientific research on a large panel of related biomarkers, NeuroSense's strategy is to develop combined therapies targeting multiple pathways associated with these diseases. For additional information, we invite you to visit our website and follow us on LinkedIn, YouTube and X. Information that may be important to investors may be routinely posted on our website and these social media channels. Forward-Looking Statements This press release contains "forward-looking statements" that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will" "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on NeuroSense Therapeutics' current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict and include statements regarding a commercial launch in Canada and market potential. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. The future events and trends may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward looking statements. These risks include the risk that that the commercial launch of PrimeC will not expeditious, that there will not be dependable and compliant sourcing for commercial-scale production volumes of PrimeC, that the shelf life of PrimeC will not be as anticipated, lower than anticipated market opportunity in Canada and elsewhere, that regulatory approvals for PrimeC will be delayed or not obtained in Canada or elsewhere; insufficient capital to complete development of PrimeC, the timing of expected regulatory and business milestones; the potential for PrimeC to safely and effectively target ALS; preclinical and clinical data for PrimeC; the uncertainty regarding outcomes and the timing of current and future clinical trials; the development and commercial potential of any product candidates of Neurosense; the ability of NeuroSense to remain listed on Nasdaq; and other risks and uncertainties set forth in NeuroSense's filings with the Securities and Exchange Commission (SEC). You should not rely on these statements as representing our views in the future. More information about the risks and uncertainties affecting NeuroSense is contained under the heading "Risk Factors" in the Annual Report on Form 20-F filed with the Securities and Exchange Commission on April 7, 2025 and NeuroSense's subsequent filings with the SEC. Forward-looking statements contained in this announcement are made as of this date, and NeuroSense undertakes no duty to update such information except as required under applicable law. Logo: SOURCE NeuroSense WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED