Diclofenac Epolamine

Compact packaging helps simplify storage, ease inventory concerns, and make daily pharmacy operations more manageable PARSIPPANY, N.J.--(BUSINESS WIRE)-- YARAL Pharma Inc. (YARAL Pharma), the rapidly growing U.S. generics subsidiary of IBSA (Institut Biochimique SA), today announced that its Diclofenac Epolamine Topical System 1.3% , the authorized generic of Flector ® (diclofenac epolamine) topical system 1.3%, is now available in a 15-count carton. Designed to meet the operational needs of today’s pharmacies, the new 15-count configuration helps pharmacists reduce clutter, optimize storage space, and manage inventory with greater flexibility, while continuing to provide patients with the same trusted therapy. “As pharmacy shelves, drawers, and bins become increasingly crowded, thoughtful packaging makes a difference,” said Stephen Beckman, CEO of YARAL Pharma. “Our 15-count Diclofenac Epolamine Topical System delivers the same product patients and pharmacists rely on, now in a smaller footprint that can save up to 50% of shelf space compared to the 30-count carton.” With its compact size and practical design, the 15-count Diclofenac Epolamine Topical System offers several advantages for pharmacies: Space-Saving & Organized Storage – A smaller carton height reduces clutter, simplifies stacking, and fits easily into limited shelf, drawer, or bin space. Streamlined Workflow – Easier to locate, stock, and access during daily operations, helping reduce time spent managing inventory. Flexible Inventory Management – The smaller pack size supports more efficient stocking, helps prevent over-ordering, and allows pharmacies to better match inventory to demand – especially when space is limited. Product Information YARAL Pharma’s Diclofenac Epolamine Topical System 1.3% is a nonsteroidal anti-inflammatory drug (NSAID) and is indicated for the topical treatment of acute pain due to minor strains, sprains, and contusions in adults and pediatric patients 6 years and older. Product NDC Number Dimensions 15-Count (3 envelopes per carton) * NDC 82347-0405-6 8.25” x 6.124” x 1.375” 30-Count (6 envelopes per carton) * NDC 82347-0405-5 8.25” x 6.124” x 2.375” *Packaged 5 topical systems per envelope YARAL Pharma’s Diclofenac Epolamine Topical System 1.3% 15-count is now available. For more information, email info@yaralpharma.com or call (866) 218-9009. USE DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% is prescription medication that is applied to the skin to treat acute pain from minor strains, sprains, and contusions (bruises) in adults and pediatric patients 6 years and older. DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% contains diclofenac epolamine (a non-steroidal anti-inflammatory drug or NSAID). IMPORTANT SAFETY INFORMATION What is the most important information I should know about DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3%? DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% is a nonsteroidal anti-inflammatory drugs (NSAID). NSAIDs can cause an increased risk of heart attack or stroke that can lead to death. This may happen early in treatment and may increase with increasing doses of NSAIDs and with longer use of NSAIDs. Do not take DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% right before or after a heart surgery called “coronary artery bypass graft” (CABG). Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack. NSAIDs can cause an increased risk of bleeding, ulcers, and tears (perforation) of the esophagus, stomach, and intestines: at any time during treatment without warning may cause death. The risk of getting an ulcer or bleeding increases with: a history of stomach ulcers, or stomach or intestinal bleeding with the use of NSAIDs taking medicines called “corticosteroids”, “anticoagulants”, “SSRIs”, or “SNRIs” increasing doses of NSAIDs longer use of NSAIDs smoking drinking alcohol older age poor health advanced liver disease bleeding problems NSAIDS should only be used: exactly as prescribed at the lowest dose possible for your treatment for the shortest time needed Who should not take DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3%? Do NOT take DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% if you have a known hypersensitivity reaction to diclofenac or any component of the drug product. Do NOT take DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% if you have had an asthma attack, hives, or other allergic reactions to aspirin or any other NSAID medicine. DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% should never be used right before or after heart bypass surgery. Do NOT apply DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% to open wounds, cuts, burns, infected, or damaged skin. Before taking NSAIDS, tell your healthcare provider about all of your medical conditions, including if you: have liver or kidney problems have high blood pressure have asthma are pregnant or plan to become pregnant. Taking NSAIDs at about 20 weeks of pregnancy or later may harm your unborn baby. If you need to take NSAIDs for more than 2 days when you are between 20 and 30 weeks of pregnancy, your healthcare provider may need to monitor the amount of fluid in your womb around your baby. You should not take NSAIDs after 30 weeks of pregnancy. are breastfeeding or plan to breast feed. Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins, or herbal supplements . NSAIDs and some other medicines can interact with each other and cause serious side effects. Avoid using DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% with other NSAIDs or salicylates (e.g., diflunisal, salsalate). NSAIDs may be available as over-the-counter medications for treatment of colds, fever, or insomnia. Do not start taking any new medicine without talking with your healthcare provider first. Especially tell your doctor if you take: aspirin--Do not use low dose aspirin with DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% until you talk to your healthcare provider. any anticoagulant medicine such as warfarin steroid medications including corticosteroids antidepressant medicines including “SSRIs” or “SNRIs” Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine. What are the possible side effects of NSAIDs? See “What is the most important information I should know about DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3%?” NSAIDs can cause serious side effects, including: new or worse high blood pressure heart failure liver problems including liver failure kidney problems including kidney failure low red blood cells (anemia) life-threatening skin reactions life-threatening allergic reactions Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness The most common side effects of DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% were itching and nausea in adults, and headache and itching in pediatric patients. Get emergency help right away if you get any of the following symptoms: shortness of breath or trouble breathing, slurred speech, chest pain, swelling of the face or throat, or weakness in one part or side of your body. Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms: nausea vomit blood more tired or weaker than usual there is blood in your bowel movement, or it is black and sticky like tar diarrhea itching unusual weight gain your skin or eyes look yellow skin rash or blisters with fever indigestion or stomach pain swelling of the arms, legs, hands, and feet flu-like symptoms If you take too much of your NSAID, call your healthcare provider or get medical help right away. These are not all the possible side effects of DICLOFENAC EPOLAMINE TOPICAL SYSTEM 1.3% or NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs or for advice about side effects. You are encouraged to report side effects to YARAL Pharma Professional Information Service at 1-866-218-9009 or FDA at 1-800-FDA-1088 or . Please see the Full Prescribing Information, including BOXED WARNING and Patient Information at About YARAL Pharma YARAL Pharma Inc. (Parsippany, N.J.) is the U.S. generics subsidiary of IBSA, a global pharmaceutical company headquartered in Switzerland. By focusing on people and innovating the ways they’re cared for, YARAL Pharma is proud to offer the same values and expertise of its parent company to the U.S. market. Dedicated to ensuring access to affordable authorized generics (AGs) and complex generic medicines that enhance healthcare outcomes, YARAL Pharma offers its customers high-quality products across a range of therapeutic areas, continuity of supply, and a commitment to exceptional customer service. For more information, visit or contact info@yaralpharma.com or 866-218-9009. About IBSA IBSA (Institut Biochimique SA) is a Swiss pharmaceutical multinational with 20 subsidiaries across Europe, China, and the United States. Its products are available in over 90 countries, and its R&D activities focus on 10 therapeutic areas. In 2025, IBSA celebrated the 40 th anniversary of its acquisition by current President and CEO, Arturo Licenziati, who has transformed the company into a multinational corporation employing over 2,500 personnel worldwide. IBSA’s growth and development can be attributed to its ability to innovate by refining well-known molecules, as well as to its commitment to looking to the future responsibly and transparently, thanks to the dedication and dynamism of its people. Flector ® is a registered trademark of IBSA Institut Biochimique S.A. YPM-1500-EN-v1 Contacts Media Daina Basile Kovak-Likly Communications dbasile@klcpr.com

2. 作用机制与工作模式 2.1 光遗传学工具 光遗传学工具利用发色团或光敏辅因子吸收光子，引发光化学反应，从而在蛋白质的失活与激活状态间切换。其核心优势在于可逆性和卓越的时空分辨率。根据作用机制，可分为以下五类。 2.1.1 光学异源二聚体 此类工具通过光控的异型蛋白质相互作用实现功能调控。广泛使用的光敏模块（PSM）包括燕麦光氧电压（LOV）域、拟南芥隐花色素（CRY）、真菌光受体Vivid（VVD）以及源自细菌（BphPs）和植物（PHYs）的光敏色素。例如，基于燕麦LOV2结构域改进的光诱导二聚体（iLID）系统，在蓝光刺激下可诱导细菌肽SsrA与其结合伙伴SspB的相互作用。CRY2与隐花色素相互作用碱性螺旋-环-螺旋蛋白1（CIB1）系统则依赖光诱导的CRY2结构变化，暴露与CIB1的结合界面。这些系统在操纵基因表达、亚细胞定位、酶活性和细胞信号传导中应用广泛。为克服蓝光组织穿透浅的局限，基于植物光敏色素B（PhyB）与光敏色素相互作用因子（PIF）的红光/远红光系统（PhyB/PIF）及其他利用哺乳动物内源性胆绿素作为辅因子的远红光系统（如BphP1-PpsR2、nanoRed、MagRed）被开发出来，增强了在体应用的兼容性。 2.1.2 光诱导同源寡聚化 CRY2和VVD在光刺激下也能介导自身寡聚化。例如，CRY2可形成光诱导的同源寡聚体（推测为四聚体），其E498G突变体（CRY2olig）或附加C端9肽的变体（CRY2clust）可增强聚类效率。荧光蛋白Dronpa的145N突变体则在500 nm光照下通过发色团从顺式（cis）到反式（trans）的构型变化，实现从四聚体到单体的解离。 2.1.3 光触发构象开关 微生物和动物视蛋白是典型的由光诱导构象变化驱动的工具。例如，源自莱茵衣藻的通道视紫红质2（ChR2）是光遗传学的基石，蓝光照射使其视网膜发色团发生光异构化，打开通道，允许阳离子跨质膜流动，撤光后通过热弛豫迅速关闭。动物视蛋白则是一类光敏G蛋白偶联受体（GPCR），通过将视蛋白与不同GPCR融合创建的Opto-GPCRs（如OptoXRs、Opto-mGluR6、基于黑视蛋白的Opto-GPCRs），能以光非侵入性地控制胞内信号通路。 2.1.4 光依赖性蛋白质切割 该策略通过将光开关模块整合到蛋白酶中来实现光控蛋白水解。例如，将CRY2/CIB1或pMag模块分别与分裂的烟草蚀纹病毒蛋白酶（TEVp）和烟草脉斑驳病毒蛋白酶（TVMVp）片段融合，可实现光诱导的蛋白酶活性重建。另一策略利用工程化的LOV结构域C端Jα螺旋在黑暗中“笼锁”TEVp切割序列（TEVcs），光照则解笼并恢复切割，此原理应用于iTango、SPARK、FLARE、FLiCre等系统。更新的LAUNCHER系统将iLID整合到环状置换的病毒蛋白酶中，实现了单组分、高效的光控有效载荷酶切释放。此外，光裂解蛋白PhoCl及其改进版PhoCl2在紫光（~400 nm）刺激下可通过不可逆的光裂解实现蛋白质解离。 2.1.5 光诱导蛋白质降解 大多数系统利用真核细胞的蛋白酶体实现光诱导的靶蛋白降解。一种方法是通过光诱导异源二聚化，将E3泛素连接酶或其接头蛋白招募至靶蛋白，促进其泛素化和降解，例如LiPD和OptoΔ2Trim-TPD系统。另一种策略是利用光诱导的包含三结构域蛋白21（TRIM21）RING结构域的聚类来促进降解。第三种方法则是利用工程化的LOV2结构域笼锁一个降解决定子（degron），光照时暴露该决定子以启动降解。 2.2 化学遗传学工具 化学遗传学工具通常依赖于配体诱导的蛋白质与配体之间的非共价相互作用，介导化学诱导的接近（CIP）或化学破坏的接近。 2.2.1 异型相互作用 FK506结合蛋白（FKBP）-雷帕霉素-FKBP-雷帕霉素结合域（FRB）系统是最早且应用最广泛的异型相互作用化学遗传学工具之一。雷帕霉素可诱导FKBP和FRB形成三元复合物。通过“碰撞-空穴”策略对其进行改造，可提高其在哺乳动物细胞中的特异性。植物来源的脱落酸（ABA）、赤霉酸以及新型系统如INSPIRE、CATCHFIRE和SAMBA（基于烟草水杨酸受体）也提供了多样化的配体诱导异源二聚化平台。人工智能的进步加速了针对用户指定化学触发剂（如抗病毒药、抗癌药）的全新化学遗传系统的设计。 2.2.2 同型相互作用 同型工具可实现相同蛋白质的聚类，为高阶组装提供了高效补充方案。早期例子包括利用合成配体诱导FKBP融合的T细胞抗原受体（TCR）聚类以激活T细胞。基于抗咖啡因纳米抗体进化而来的遗传编码咖啡因操作合成模块（COSMO），对咖啡因具有高敏感性，其双价形式（biCOSMO）可在咖啡因存在时发生分子内二聚化，实现精确的功能调控。B细胞淋巴瘤6的BTB域（BTBBCL6）及其配体BI-3802/BI-3812则提供了可逆的药物诱导寡聚化开关。 2.2.3 构象变化 此策略通过配体诱导的构象变化实现对蛋白质活性的条件性控制，在GPCR工程中尤为突出。由人M3毒蕈碱受体改造而来的Gq偶联的DREADD hM3Dq是一个经典例子，它可选择性地被氯氮平-N-氧化物（CNO）激活，进而激活磷脂酶C（PLC）信号通路，导致细胞内钙动员和神经元兴奋。此外，Gi和Gs偶联的DREADD、KORD（被Salvinorin B激活）以及可编程的抗原门控GPCR工程受体（可检测多种抗原）极大地扩展了化学遗传学工具箱。 2.2.4 可控蛋白水解切割 Tango系统利用配体诱导的β-arrestin向人精氨酸加压素受体2的募集，触发TEVp介导的膜锚定转录因子切割，进而激活基因转录。其改进版PRESTO-Tango实现了高通量GPCR筛选。ChaCha系统则将配体传感与CRISPR基因组调控结合，实现配体依赖、可逆的内源基因表达控制。此外，丙型肝炎病毒蛋白酶（HCVp）及其FDA批准的抑制剂（如grazoprevir）被重新用于调控外源引入的HCVp活性。分裂蛋白酶-可切割正交卷曲螺旋（SPOC）逻辑电路整合了多种化学诱导二聚化系统和正交蛋白酶，构建了配体控制的多层蛋白水解信号通路。 2.2.5 条件性降解 此类工具可实现靶蛋白的快速选择性清除。生长素诱导降解决定子（AID）系统改编自植物生长素信号，利用F-box蛋白OsTIR1招募生长素标记的靶蛋白进行快速的蛋白酶体降解。其改进版AID2通过“碰撞-空穴”策略显著提高了特异性和降解效率。降解标签（dTAG）系统则利用dTAG-13等异双功能降解剂，将FKBP12-F36V标记的蛋白质募集到E3连接酶（如cereblon或von Hippel-Lindau蛋白）进行降解。另一种策略是利用小分子稳定不稳定的结构域，撤去配体则触发降解，例如可被雷帕霉素衍生物C20-MaRap选择性稳定的突变FRB。 3. 对生理过程的远程控制 3.1 细胞器定位与运输 光遗传学通过光控募集驱动蛋白和动力蛋白等马达蛋白，可精确控制过氧化物酶体、循环内体、线粒体等细胞器的空间定位，用于研究轴突生长调控等过程。光控膜接触位点形成工具（如OptoPBer、LiMETER）能够调节内质网-质膜等细胞器间的距离，并操控蛋白质复合物扩散。化学遗传学方法则通过化学诱导二聚化（CID）实现马达蛋白的持续募集，用于研究细胞内运输动力学。在细胞核内，CRISPR-基因组组织（CRISPR-GO）系统可化学诱导基因组位点与核周、Cajal小体等亚核区室的可逆性重定位，以研究三维基因组组织。 3.2 钙通道调控 光可激活的钙内流工具主要靶向钙释放激活钙（CRAC）通道。例如，Opto-CRAC、BACCS利用LOV2域笼锁基质相互作用分子1（STIM1）的ORAI激活区域，蓝光暴露时解笼以激活ORAI通道。光诱导STIM1聚类工具（如optoSTIM1、monSTIM1）则通过CRY2-STIM1融合体实现快速钙内流。为克服对内源性ORAI的依赖，光操作钙通道（LOCa）在工程化的ORAI1突变体（H171D/P245T）中插入LOV2，实现了STIM1非依赖的光控门控。化学遗传学方面，咖啡因操作合成模块融合STIM1胞质片段（COSMO-STIM1ct）等系统可通过小分子（如咖啡因、雷帕霉素类似物）诱导STIM1二聚化或寡聚化，从而触发钙内流。 3.3 程序性细胞死亡 光遗传学工具可为细胞死亡途径提供精确的时空控制。例如，光激活的胱天蛋白酶-7（caspase-7）开关或光诱导的Bax向线粒体易位可触发凋亡。光诱导坏死性凋亡或焦亡1（LiPOP1）系统利用CRY2诱导的MLKL寡聚化及质膜转位执行坏死性凋亡。光激活RIPK3（La-RIPK3）也能诱导溶解性细胞死亡。焦亡可通过光诱导GSDMD N端与C端抑制域的解离/切割、cpLOV2笼锁GSDMD N端或光诱导人caspase-1聚类来触发。化学遗传学方面，诱导性胱天蛋白酶9（iCasp9）系统已在临床试验中作为过继性T细胞疗法的安全开关，用于控制移植物抗宿主病（GVHD）。基于咖啡因的COSMO系统也能诱导快速的MLKL介导的坏死性凋亡。 3.4 基因组编辑 为实现 CRISPR 系统时空可控的基因编辑，光遗传学策略包括利用pMag等光开关蛋白的重组来激活分裂的Cas9（paCas9），或通过将光敏模块（如LOV2）整合到抗CRISPR（Acr）蛋白（如AcrIIA4）中，开发出光依赖的CRISPR-Cas9活性开关（如CASANOVA、LiCASINO）。为增强组织穿透，还开发了远红光激活的分裂Cas9（FAST）系统。化学遗传学则利用FKBP-FRB、ABA等化学诱导二聚化系统来控制分裂Cas9、碱基编辑器或Cas13b/dCas13b的组装与活性，实现药物调控的基因组或RNA编辑。 3.5 免疫调节 为克服传统CAR-T细胞疗法中失控激活、毒性等问题，可远程调控的CAR-T系统被开发出来。光遗传学策略包括光诱导CAR在T细胞表面表达（如LINTAD系统）或光控分裂CAR组分在质膜附近重组（如LiCAR-T、optoCAR）。LiCAR-T结合上转换纳米板，可将近红外光转换为蓝光，实现对深部组织CAR-T功能的无线、非侵入性控制。光遗传学工具还可通过刺激先天免疫信号（如利用Opto-CRAC激活树突状细胞，或利用LiSmore激活STING通路）间接增强抗肿瘤免疫。化学遗传学策略则利用FKBP-FRB二聚化或丙型肝炎病毒（HCV）NS3蛋白酶等系统，使CAR-T细胞的激活严格依赖于小分子药物（如AP21967、grazoprevir）的给予，从而提供安全开关。 3.6 神经调控 光遗传学通过光诱导受体酪氨酸激酶（RTK）二聚化（如optoTrkA、optoFGFR1）或下游信号分子（如Raf、AKTΔPH）的膜招募（optoRAF、optoAKT），精确模拟神经营养因子信号，在细胞模型和果蝇、小鼠等模式生物中成功促进了轴突再生、缓解了帕金森病模型症状，并揭示了其在突触可塑性与学习记忆中的作用。光控突触沉默工具optoSynC则能通过光诱导突触小泡聚类可逆地抑制神经递质释放。化学遗传学方面，设计师药物独家激活的设计师受体（DREADDs，如hM3Dq、hM4Di、KORD）通过选择性响应合成配体（如CNO、Salvinorin B）来增强或抑制神经元活性，已成为在多种物种中解析神经环路与行为机制的核心工具。为提高临床转化潜力，新一代配体如去氯氯氮平、奥氮平已被探索用于激活DREADDs。 4. 光遗传学与化学遗传学工具的比较 光遗传学工具具有激活快速、可逆性高、空间精度卓越等优点，非常适合研究需要精确时空控制的动态生理过程。但其持续激活需要光照，可能引起组织发热和光毒性，且可见光组织穿透力有限（<1–3 mm），针对深部组织的应用面临挑战。化学遗传学工具虽然通常较慢、可逆性较低，但能提供更持久、可调谐的控制，更适用于慢性在体研究。其依赖配体给药，无需持续刺激，减少了细胞应激，且小分子可通过口服、静脉等非侵入方式递送，在临床转化上更具便利性。 5. 临床转化 光遗传学的临床转化在视觉修复方面取得里程碑进展，一项针对晚期视网膜色素变性患者的临床试验通过AAV递送红光敏感视蛋白ChrimsonR，配合光放大护目镜，实现了部分视觉恢复。化学遗传学则在细胞疗法安全性方面展现价值，iCasp9自杀基因系统在单倍体相合造血干细胞移植的临床试验中，能有效、安全地清除输注的T细胞以控制移植物抗宿主病。然而，基于化学诱导接近策略调控CAR-T细胞的临床试验也出现过严重不良事件，凸显了开发更安全、精准调控系统的必要性。 6. 总结与展望 光遗传学与化学遗传学通过实现对蛋白质活性和细胞功能的精确、可调、可逆控制，革新了生理学的机制研究与转化研究。二者各有优势，临床转化路径各异。随着人工智能预测蛋白质结构等技术的发展，下一代工具的设计将更加理性化。将这些策略整合到生物制剂和工程化细胞疗法（尤其是下一代CAR-T疗法）中，正在通过实现对适应性免疫和先天免疫的远程精确控制，改变免疫治疗格局。这些创新有望带来更安全、精准的疗法，推动个性化医疗在疾病管理中的实现。