Uveitis, Posterior

摘 要 驻景丸是 2023 年《古代经典名方目录（第二批）》汉族医药的第 40 首，出自北宋《太平圣惠方》，由菟丝子、车前子、熟地黄 3 味药组成，功用补益肝肾、清热明目，主治肝肾亏虚之眼病，为中医眼科临床常用名方。采用文献统计学方法，搜集分析驻景丸的古今文献，共筛选有效古籍数据 63 条，涉及 47 部中医古籍。从驻景丸的方源方名、组成剂量、药物基原与炮制、制法用法、主治功效等方面进行系统梳理，总结其方证关键信息。研究发现，驻景丸中菟丝子、车前子、熟地黄的配比为 5∶3∶3 是采用《太平惠民和剂局方》所载剂量；《黎居士简易方论》首载加减驻景丸，该方的主治范围与原方相仿，但药效更全面有力，历代应用更加频繁；现代医家继续对驻景丸进行化裁，提出驻景丸加减方、通络驻景丸等衍生方，广泛应用于眼科临床，取得良好效果。驻景诸方以滋补肝肾为本，或兼宁心安神，或兼清热利湿，或兼化瘀通络，然其对应的病机根本在于肝肾虚损，导致目力不足、障翳昏花。驻景诸方在老年性眼病、其他老年退行性改变及青少年近视的防治方面均有良好应用前景，后续可开展相关药理研究和制剂研发。2023 年 9 月，国家中医药管理局会同国家药品监督管理局联合发布了《古代经典名方目录（第二批）》[1]（以下简称《目录》），驻景丸入选经典名方汉族医药第 40 首。驻景丸始载于《太平圣惠方》[2]，由菟丝子、车前子、熟地黄组成，功能补益肝肾、清热明目，眼科临床应用甚多，主要用于肝肾亏虚之老年眼病。本研究查阅相关文献发现，驻景丸的文献研究尚缺乏系统梳理，尽管少数研究[3-6]曾就驻景诸方的沿革演变展开探讨，但存在古代文献失考之不足，且缺乏药物炮制、配比差异、折算剂量等关键信息的考证。本研究基于《古代经典名方关键信息考证原则》[7]提出的相关要求，以历代医籍记载为依据，厘清驻景丸的历史发展脉络，以现行标准规范为参照，探讨其关键方证信息，将为驻景丸相关制剂的研发申报和质量控制提供科学依据。1 资料与方法1.1 文献数据来源古籍文献基于《中华医典》V5.0 数据库[8]、中医智库（https://zhongyigen.com/#）、读秀数据库（https://www-duxiu-com.libproxy1.nus.edu.sg/）、山西中医药大学图文信息中心（https://twxxzx.sxtcm.edu.cn/）等资源进行辑录，以“驻景丸”及异名“驻景圆”为主要检索词，并检索“菟丝子-车前子-熟地黄”药物配伍组合，获取驻景丸相关的方药组成、药物剂量、功效主治、煎服法等古籍数据，结合纸质版书籍予以校正。现代文献通过中国知网数据库，以“驻景丸”为主题词或关键词进行检索，获取相关的临床研究文献。1.2 纳入与排除标准1.2.1 纳入标准古籍文献：1）1911 年以前的中医古籍，同一古籍有不同版本则纳入较早版本或公认的善本；2）明确驻景丸的组成、炮制、剂量、主治病证、煎服法等方证信息；3）忽略药物名称之间的区别，如菟丝、菟丝饼与菟丝子，熟地、熟地黄与熟干地黄，前仁、车前与车前子等。现代文献：与驻景丸及其类方相关的临床研究。1.2.2 排除标准古籍文献：1）只检索到方剂名而无具体的药物组成、剂量、主治等方证信息可用者；2）方名相同，但组成或功效主治不同的“同名异方”；现代文献：1）驻景丸相关的综述、理论探讨和实验研究类文献；2）以驻景丸作为对照组的研究。1.3 数据规范1）古籍文本辑录包括古籍名称、成书年代、编著者、方名、药物组成、功效主治、煎服法等信息；2）病证名称、药物名称和剂量单位以原文记载为准，尽量保持古籍信息原貌，确保文本辑录的准确性；3）采用双人双录入方法，有争议的文献由本文通讯作者参与协商、达成共识，确保文献来源的准确性。2 古籍文献分析2.1 古籍记载情况经文献检索及筛选，共辑录驻景丸相关的古代文献数据 63 条，涉及中医古籍 47 部；在朝代分布上，宋代、元代、明代、清代古籍分别有 6、4、16、20 本，另有海外古籍 1 本（约成书于 1331 年日本镰仓时代）；医籍类别方面，涵盖综合性医著 17 本、方书 16 本、本草 3 本、诊法 2 本及 9 本中医眼科专著。历代古籍对于驻景丸的记载略有不同，其方名、出处、药物组成、剂量、功效主治记载，详见增强出版附加材料。2.2 驻景丸的历史源流与方名分析驻景丸出处为宋代王怀隐《太平圣惠方》（以下简称《圣惠方》），此书为北宋官修的第一部大型医药方书，集宋代以前医药之大成[9]。《圣惠方》[2]载：“治肝肾俱虚，眼常昏暗，宜服驻景圆方。菟丝子五两（酒浸三日，曝干，别捣为末），车前子一两，熟干地黄三两。”《目录》中车前子取三两为用，源于《太平惠民和剂局方》[10]247（以下简称《局方》）对药物剂量的调整，将菟丝子、车前子、熟地黄的药量比改为 5:3:3，后世医籍所载驻景丸多据此比例组方。驻景丸最早记载为“驻景圆”，此乃“丸”字避讳的结果，北宋靖康之后，因避宋钦宗赵桓名讳，南宋及部分金元医书中常见“丸”字易为“圆”或“元”[11]。《圣惠方》和《局方》现存最早刊本均出自南宋绍兴年间[9,12]，故产生“驻景圆”之异名，元代以后成书或刊刻的医籍，无须避宋讳，故改回“驻景丸”之名。驻景丸的“景”字在金文的本义指太阳在亭台上投下的影子，即日影[3]，《说文解字》载：“景，光也”，“景”字以日光、日影代指人眼所见之事物。明代李梃《医学入门》[13]9 释曰：“日光之影为景，没则昏矣，言药能驻景，使不昏也”，取名驻景强调其明目之效。此外，“景”字能延伸为时光、光景之义，清代黄庭镜《目经大成》[14]云：“方名驻景，要以得此聊以销病居之岁月云”，表明“驻景”二字有却病延年、长生久视的含义。2.3 驻景诸方的组成分析经统计，记载驻景丸药物组成的条文共 63 条，其中 19 条与《目录》记载一致，仅含菟丝子、车前子、熟地黄 3 味药。涉及药味加减变化的条文有 44 条，其中减去熟地，守菟丝子、车前子两药的记载首见于苏颂《本草图经》，但该书未载剂量及功效，仅言“驻景丸用车前、菟丝二物，蜜丸，食下服，古今为奇方”[15]。在宋徽宗赵佶敕编的《圣济总录》[16]中，驻景丸的组方与《圣惠方》所载有异，由车前子、菟丝子两药，合决明子、羚羊角、防风而成，5 味药各等分，炼蜜和丸，用治目视䀮䀮。然而回溯《圣济总录》驻景丸之方源，发现该方在《圣惠方》中名曰“车前子圆”，列于驻景圆之前，两方功效相近，疑是《圣济总录》编撰时误其方名。本研究发现最早的驻景丸化裁方，称作加减驻景丸，出自南宋黎民寿《黎居士简易方论》[17]，在原方三药基础上，加当归、五味子、枸杞子、楮实子、川椒而成，后世驻景丸变方基本遵循此例。加减驻景丸相关的古籍记载共 38 条，该方在后世医籍中较原方更常见，其方名又称简易加减驻景丸、加味驻景丸，有些医籍甚至混称为驻景丸。倪维德《原机启微》[18]所载“简易加减驻景丸”，仅将黎氏方中的车前子用量由三两减为二两，方名增“简易”二字，表明其源于《黎居士简易方论》，而非倪氏原创；张时彻《摄生众妙方》[19]将加减驻景丸中的五味子换为五倍子，方名称作“驻景丸”或“补肾丸”；武之望《济阳纲目》[20]调整部分药物剂量，方名称作“加味驻景丸”。尽管存在方名混称现象，多数医籍收录加减驻景丸基本沿用《黎居士简易方论》所载药味，或进行药物剂量的变化。在眼科专著中，成书于明代而托名孙思邈的《银海精微》[21]共记载 4 种驻景丸，加减驻景丸的组成与此前医籍一致，前两首驻景丸主要加入人参、乳香、肉苁蓉 3 味药，另一首方名曰“驻景补肾明目丸”，增加石斛、磁石、青盐、沉香等药。此外，黄庭镜《目经大成》[14]载有一首驻景丸，由枸杞、地黄、苁蓉、当归、阳起石、磁石等 15 味药，加龟胶鹿胶合蜜、朱砂为衣而成，主治“目昏涩泣出，时见黑花”，与经典名方驻景丸的功效主治虽相近，但两者实为“同名异方”。2.4 药物基原与炮制分析本研究参考《目录》对驻景丸的记载，结合《中华人民共和国药典》[22]（以下简称《中国药典》）2020 年版、地方炮制规范、古代本草典籍及现代本草考证成果，确定驻景丸组成药物的基原与炮制规格。由于历代古籍记载加减驻景丸的频次比原方更多，考虑经典名方相关制剂的开发和临床应用的拓展，本研究将加减驻景丸中 5 种加味药物（当归、楮实子、五味子、枸杞子、川椒）纳入考证范围，以完善文献梳理工作。统计历代古籍中驻景丸组成药物的炮制方法，每味药物的炮制情况见表 1。2.4.1 菟丝子《中国药典》记载菟丝子为旋花科植物南方菟丝子 Cuscuta australis R. Br.或菟丝子 C.chinensis Lam.的干燥成熟种子[22]322，参考国家中医药管理局发布的《古代经典名方关键信息表》[23]对菟丝子基原的确认，建议选择旋花科植物菟丝子作为入药基原。《目录》提及菟丝子的炮制方法为“酒浸三日，曝干，别捣为末”，菟丝子在驻景丸中主要采用酒制规格。尽管《中国药典》2020 年版收载菟丝子的现代炮制方法为盐炙，但参考经典名方炮制考证实施细则[24]，可采纳地方炮制规范所载的炮制品，经查在山东省[25]、湖南省[26]、黑龙江省[27]等地方标准中均收载了酒菟丝子及其制备方法，说明现代仍保留酒菟丝子的炮制工艺。《本草经集注》[28]记载菟丝子“宜丸不宜煮，得酒良”，强调酒菟丝子功效更佳，适合入丸剂；汪小莉等[29]发现，酒浸法炮制菟丝子在历代本草典籍中占主流地位；杨颂等[30]、赵唯年等[31]研究表明，酒菟丝子的黄酮类活性成分高于盐炙品；此外，菟丝子经过酒制能够引药上行、增强补益肝肾的作用，符合驻景丸治疗眼目疾患的特点。因此，建议驻景丸中的菟丝子用旋花科植物菟丝子的干燥成熟种子，炮制方法为酒制。2.4.2 车前子《中国药典》2020 年版记载车前子为车前科植物车前 Plantago asiatica L.或平车前 P.depressa Willd.的干燥成熟种子[22]69，姚闽等[32]结合文献和市场调查，发现车前的应用历史较悠久，是现行车前草及车前子的主流商品基原；高武等[33]考证历代车前子的品种来源，认为车前是历代车前子的主要基原植物，平车前的种子在民国时期才作车前子流通；参考已发布的《古代经典名方关键信息表》，建议以车前作为经典名方的入药基原。《目录》对驻景丸中的车前子无炮制要求，《圣惠方》《局方》两部早期文献也未注明车前子的炮制。车前子炒制的记录共 18 次，约占有效数据的 28.57%，于大猛等[34]认为古代炒制车前子主要使其易于粉碎，从而煎出有效成分，故《局方·论炮炙三品药石类例》[10]423载车前子：“凡使须微炒燥，方入药用，如只焙干亦得。”部分医家认为车前子需经过炒制、焙干，可能缘于方便入药的考虑，也体现古人“逢子必炒”的炮制习惯[35]。鉴于驻景丸原文未对车前子的炮制作出要求，方中的车前子主要取其寒性，既泻肝肾之邪热，又制熟地之滋腻，故无需进行炒制，以免改变药性，影响全方疗效。因此，建议驻景丸的车前子选用车前科植物车前的干燥成熟种子，药物规格为生品。2.4.3 熟地黄《中国药典》规定地黄的来源为玄参科植物地黄 Rehmannia glutinosa Libosch.的新鲜或干燥块根，鲜用者称鲜地黄，焙干后习称生地黄[22]129。熟地黄乃生地黄加工而成，《中国药典》2020 年版记载的炮制方法有酒炖法和蒸法[22]130。徐大椿《神农本草经百种录》[36]记载：“熟地黄乃唐以后制法，以之加入温补肾经中药颇为得宜”，最早记载地黄九蒸九晒加工方法为唐代《千金翼方》的“造干地黄法”[37]，宋代则出现对地黄“蒸九遍用酒制造”和“洒酒九蒸九曝”的酒蒸法[38]。酒蒸法和清蒸法处理熟地，其功效略有区别：清蒸熟地主滋阴补血、填精益髓，但容易滋腻碍脾；酒蒸熟地可借酒力行药势、通血脉，更利于补阴血，使其补而不腻[38]。采用酒蒸熟地能在一定程度上祛弊就利，防其滋腻凝滞，存其补血之用。因此，建议驻景丸的熟地黄选用玄参科植物地黄的干燥块根，炮制方法为酒蒸。2.4.4 加减驻景丸中的加味药加减驻景丸普遍增加了当归、楮实子、五味子、枸杞子、川椒 5 种药物，经考证，当归[39]、楮实子[40]、五味子[41]、枸杞子[42]的用药基原与《中国药典》2020 年版的记载一致，推荐加减驻景丸中当归采用伞形科植物当归 Angelica sinensis (Oliv.) Diels 的干燥根[22]139，楮实子采用桑科植物构树 Broussonetia papyrifera (L.) Vent.的干燥成熟果实[22]349，五味子（北五味子）采用木兰科植物五味子 Schisandra chinensis (Turcz.) Baill.的干燥成熟果实[22]68，枸杞子采用茄科植物宁夏枸杞 Lyciumbarbarum L.的干燥成熟果实[22]260。以上 4 味药在加减驻景丸的古籍记载中多以生品入药，且诸药并无炮制减毒的必要，建议沿用古代用法，均用生品入药，粉碎研末入丸。《中国药典》2020 年版记载的川椒基原有 2 种，为芸香科植物青椒 Zanthoxylum schinifolium Sieb.et Zucc.或花椒 Z. bungeanum Maxim.的干燥成熟果皮[22]166。樊丹青等[43]认为青椒在古代本草中未见记载，为现代新兴品种，且青椒与花椒在生药学、药代动力学等实验中存在差异，两者同等入药的科学性有待探讨；郭延秀等[44]指出，川椒、蜀椒、秦椒均以产地命名，系芸香科植物花椒；考虑药材的道地优势，建议选择四川产区的花椒作为入药基原。按历代本草记载，花椒为辛温有毒之品，古代通过去除内壳及种子加以净制，并采用微炒加热、与他药同制等方法降低花椒毒性[45]。加减驻景丸中的川椒主要为炒制，部分古籍具体强调去目、去子、炒出火毒等要求，与现代制法基本一致。建议花椒的炮制规格为炒花椒，制法参考《中国药典》2020 年版“除去椒目、果柄等杂质……照清炒法炒至有香气”[22]167。2.5 药物剂量与制法用法分析2.5.1 药物剂量63 条关于驻景丸药物组成的条文中，共有 58 条记载了药物剂量，各药味均有剂量者55 条，剂量记载不全者 3 条。由于驻景丸和加减驻景丸的药味组成和用药比例有所不同，故统计药物剂量时分别进行整理，见表 2、表 3。驻景丸最早由菟丝子五两、车前子一两、熟地黄三两组成，经《局方》调整车前子的剂量后，菟丝子:车前子:熟地黄的配比演变为 5:3:3，后世典籍大多沿用此配比关系。南宋黎民寿在驻景丸的基础上，将菟丝子的用量增至半斤（八两），熟地黄用量增至五两，车前子保留三两剂量，加入当归五两、楮实子一两、川椒一两、五味子二两、枸杞子二两，创制了加减驻景丸。元代倪维德将车前子的用量减为二两，至此加减驻景丸中菟丝子:车前子:熟地黄的配比演变为 8:2:5，并成为主流的配比关系。综上可知，驻景丸用药配比的演变过程中，关键在于原方三味药尤其是车前子剂量的变化，反映不同医家制备处方的观点差异，表明“中医不传之秘在于量”的意义。此外，后世医家在经典名方的实践应用中，并非简单地抄录、复制原方的组成和用量，而是根据自身理解或临床经验加以调整。例如清代费伯雄认为加减驻景丸“方法甚佳，惟川椒一味辛辣耗气，必须减去”[46]，现代眼科名家陈达夫[47]认为，“温补当中，切勿误用凝滞的补药，如果误用则杂质难清”，故其应用驻景丸常减去熟地。考证处方制备方面，本研究综合历代典籍的主流记载，驻景丸各药剂量以使用频次最多为准。在古今剂量换算上，参考古今药衡的考证成果和学术界主流观点[48-49]，宋代一两以 41.3g 进行现代剂量折算。按以上标准，经典名方驻景丸的组成包括：菟丝子 206.5 g、车前子 123.9 g、熟地黄 123.9 g，三药按5:3:3 的配比组方；加减驻景丸的组成包括：菟丝子 330.4 g、车前子 82.6 g、熟地黄 206.5 g、当归206.5g、五味子 82.6 g、枸杞子 82.6 g、楮实子 41.3 g、花椒 41.3 g，原方三药按 8:2:5 的配比组方。2.5.2 制法、用法分析 本研究纳入的 63 条有效数据中，记载驻景丸制法的共 55 条，均制成丸剂，使用蜂蜜为赋形剂，炼蜜打糊为丸。蜂蜜是重要的中药炮制辅料和赋形剂，首先其含有丰富的营养成分，具滋补作用，其次炼蜜的含水量少、黏合力强、作用持久，故蜜丸常用于慢性病或需要滋补的疾病[50]。记载制丸规格大小的数据共 41 条，其中梧桐子大 40 条、绿豆大 1 条，经考证“梧桐子大”的单颗丸药，其体积约 0.25 mL，质量约 0.3 g[51]。驻景丸的用法方面，根据送服汤剂的不同，分为温酒送服（36 条），盐汤送服（22 条），茯苓、石菖蒲煎汤送服（6 条），温水服用（4 条）及清茶服用（1 条）。送服汤剂的选择与临床目的有关，温酒送服能活血行气、引药上行，盐汤送服可引药入肾，茯苓、石菖蒲煎汤既防滋腻，又能开窍豁痰。《目录》遵循《圣惠方》的用法，选择温酒送服，然笔者认为驻景丸的服法可根据患者体质或病情予以变通，肾虚明显者推荐盐汤送服，痰湿较重者建议用茯苓、菖蒲煎汤或清茶送服，临卧服用者建议温酒或温开水送服。记载丸剂用量的数据共 45 条，单次服用 30 丸出现的频数最多，共计 29 次，服用频次主要为“日二服”，与《目录》推荐的服法一致。服药时间据古籍记载主要为“空心”“食前”或“食后临卧”，与滋补药宜空腹服用的一般规律相符。综合考虑《目录》对驻景丸服法的记载及历代典籍对制法、用法的论述，笔者建议驻景丸相关制剂可制成蜜丸，药丸规格遵循“梧桐子大”的要求，每丸约 0.3 g，空腹或夜晚睡前服用，一日 2 次，一次 30 丸（约 9 g）。2.6 主治功效分析历代典籍收载驻景丸的主治功效共计 57 条，基本聚焦于眼科证治，《圣惠方》[2]载驻景丸主治“肝肾俱虚，眼常昏暗”，《局方》[10]247 载此方“治肝肾俱虚，眼常昏暗，多见黑花，或生障翳，视物不明，迎风有泪，久服补肝肾，增目力”，说明此方主要通过滋补肝肾、养血益精治疗眼疾。《灵枢·大惑论》曰：“五藏六府之精气，皆上注于目而为之精”，精气对维系眼目的生理功能至关重要，精散则视歧。肝肾二脏与目之关联十分紧密，尤其表现在肝肾亏虚之证，“目为肝窍，瞳子神光属肾，故肝肾阴虚，则目昏暗也”[52]，“肝即肾子，补肾乃肝气增盛，补虚则明利眼力也”[53]。驻景丸中的菟丝子为平补阴阳之品，善补益肝肾、固精缩尿；车前子能泻肝肾邪热，通利小便而不走精气；两药均有明目之效，合用则补肾固精、清热明目，如清代《本草详节》[54]所载：“驻景丸车前、菟丝二物甚奇……相火常宁，精窍常闭，久久精足”，加用熟地黄滋阴养血，全方补而不腻、泄而不散，既清肝肾虚热，又充肝肾精血。肝血上呈于目，目受血而能视，肾气封藏，精关得固，精气得藏，故而延年驻景。加减驻景丸在原方基础上增加药味并调整剂量，主治“肝肾气虚，视物䀮䀮，血少气多，两目渐暗”[17]，《审视瑶函》[55]记载此方：“久服能安魂定魄，补血气虚耗”。黎民寿可能认为原方补力不够，更重视血虚证治，故重用当归五两补血活血；加枸杞子二两益精明目，五味子二两补肾宁心；加楮实子一两滋肾强阴、清肝明目，川椒一两温中散寒、补肾壮阳；全方既增加补益之功，又兼顾养血活血、宁心安神。神志对于眼目证治具有重要作用；首先精气血与神志间存在相互依存关系，宁心安神有助于血气涵养，进而滋润眼目，如《医学入门》[13]351 所云：“肝之系，虽总于目，而照彻光彩，实肾精、心神所主，故补精气安神者，乃治眼之本也”；其次《素问·解精微论》曰：“夫心者，五藏之专精也，目者其窍也”，唐代王冰[56]注曰：“神内守，明外鉴，故目其窍也”，目亦可视为心之外窍，心主神志，·神志与眼目功能存在重要关联。加减驻景丸的药效更为全面有力，在后世使用更广，如《本草思辨录》[57]所言：“若以治肾虚目暗，则须如加减驻景丸制剂为得，原方尚不及之”，突出其临床价值。3 驻景丸的现代文献分析以“驻景丸”为主题检索词，查找中国知网数据库（截至 2023 年 10 月 15 日），共检索出 185 篇文献，排除文献综述、理论探讨、实验研究以及相关性较小的文献后，共获得 67 篇临床研究文献。经典名方驻景丸广泛应用于现代眼科临床，现代医家秉承“传承精华、古为今用”的精神，对其进行化裁并提出衍生方。例如，陈达夫[47]在《中医眼科六经法要》中提出驻景丸加减方，陈老认为原方的熟地黄凝滞滋腻，用紫河车代之峻补精血，加楮实子、茺蔚子、枸杞子、五味子、木瓜等药，通过滋补肝肾、疏通气血、开通玄府的方法[58]，治疗多种内障眼病。王超等[59]选用驻景丸加减方治疗视神经萎缩，治疗组的视力、视野、中医证候等指标均优于甲钴胺对照组；陈耀华等[60]用该方治疗肝肾亏虚型干眼症，患者的泪液分泌试验指标和视觉相关生活质量评分均得到明显改善；林颖等[61]用该方治疗高度近视性黄斑出血，总有效率达 93.33%，其疗效及预后均优于对照组；此外，驻景丸加减方治疗中心性浆液性脉络膜视网膜病[62]、玻璃体混浊[63]、慢性虹膜睫状体炎[64]等眼病均有报道并取得较好疗效。通络驻景丸[65-66]是驻景丸的另一首现代衍生方，在原方基础上加入三七、蒲黄活血化瘀，砂仁化湿理气，墨旱莲滋补肝肾、凉血止血，地龙清热定惊、通经活络，既保留原方补益之功，又能化瘀祛痰、活血通络，适用于痰瘀阻络为特点的眼底病变。临床观察显示，该方在治疗糖尿病视网膜病变[67]、糖尿病性黄斑水肿[68]和年龄相关性黄斑变性[69]方面疗效确切，值得临床推广应用。在其他系统疾病方面，仅有 1 篇文献应用驻景丸加减治疗甲状腺功能减退性心脏病[70]，说明现代对驻景丸的临床研究，与古代文献记载的范畴类似，以眼科的临床应用为主。4 总结通过梳理挖掘经典名方驻景丸的古代文献，结合文献考证分析该方的源流方名、药味组成、剂量配比、制法用法、功效主治、药物基原及炮制等，基本厘清驻景丸的历史沿革和发展脉络。结果表明，驻景丸首载于《太平圣惠方》，由菟丝子、车前子、熟地黄 3 味药组成，经《太平惠民和剂局方》对药物剂量的调整，后世遵循的剂量配比为 5:3:3。驻景丸功效为补益肝肾、清热明目，主治肝肾亏虚之内障眼病。驻景丸最重要的化裁方称作加减驻景丸，出自《黎居士简易方论》，增加了当归、楮实子、五味子、枸杞子、川椒 5 味药，增强补益功效的同时突出了养血活血，重在调理肝肾气虚、精血虚损之症。加减驻景丸在古代文献中的记载较原方更多，其功效更加全面，因此本研究将该方共同纳入经典名方考证范围，作为原方的补充和拓展。根据历代对药物炮制的记载，参考现代药材炮制规格，充分考虑驻景丸方义及其疾病特点，建议菟丝子、熟地黄采用酒制，花椒炒用，车前子、当归、楮实子、五味子、枸杞子选用生品规格。方中诸药研为细末后，炼蜜糊丸，每丸 0.3 g，空腹食前用淡盐水、或夜晚睡前用温酒送服 30 丸，一日 2 次。本研究参照《古代经典名方关键信息考证原则》[7]，明确关键方证信息，形成经典名方驻景丸（含加减驻景丸）的关键信息表（表 4）。注：表中折算剂量并非每次服药量，结合每服量和药物剂量比例，驻景丸的每次服药量为 9g，各药的每服量为菟丝子 4.09 g、车前子 2.45g、熟地黄 2.45 g；加减驻景丸的每次服药量为 9 g，各药的每服量为菟丝子 2.77 g、车前子 0.69 g、熟地黄 1.73 g、当归 1.73 g、五味子 0.69 g、楮实子 0.35 g、枸杞子 0.69 g、花椒 0.35 g。基于上述对驻景诸方的古今文献考证，发现其应用范围主要在于老年内障眼病，病机特点为肝肾虚损。中医学向来有治未病的理论基础，以及异病同治的辨治思路，笔者认为经典名方驻景丸不应限于老年眼病的治疗，在其他的老年退行性改变以及青少年近视的防治方面均有良好的应用前景。经典名方文献考证可为中药创新研发拓展思路，后续可开展相关的药理研究和成药研发，促进经典名方驻景丸实现更大的现代价值。[利益冲突] 本文不存在任何利益冲突。------------THE END------------点击查看：投稿获丰厚稿费关注药研 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Encinitas, California--(News - March 28, 2024) - Kiora Pharmaceuticals, Inc. (NASDAQ: KPRX), ("Kiora" or the "Company") announced that additional data from the ABACUS-1 trial has been accepted for presentation at the Association for Research in Vision and Ophthalmology (ARVO) meeting in Seattle, WA, May 5-9, 2024. The additional data includes quantitative evaluation of the functional MRI measures. Qualitative assessment of fMRI demonstrated reactivation of the regions of the brain responsible for vision in a time-dependent manner, consistent with other improvements in visual function. The presentation, titled, "Synthetic phototransduction with a light-responsive molecule (KIO-301) in advanced retinitis pigmentosa: the ABACUS-1 phase I/II trial," will be presented by Professor Robert James Casson, DPhil, Head of Ophthalmology and Visual Science at Adelaide University. The ABACUS-1 study was a Phase I/II first-in-human clinical trial of the Company's molecular photoswitch, KIO-301, in patients with late-stage retinitis pigmentosa (RP). Initial preliminary topline results from ABACUS-1 were announced at the American Academy of Ophthalmology (AAO) annual conference in November 2023. Presentation details: Presentation #: 407 Session Title: Retina miscellaneous: Translational Date: May 5, 2024 Time: 2:00 PM Pacific Daylight Time About KIO-301 KIO-301 is a small molecule photoswitch. It is designed to selectively confer light-sensing capabilities to retinal ganglion cells (RGCs). In healthy eyes, light is first converted to electrical signals via the rods and cones (photoreceptors) and transmitted through RGCs to the vision perceiving part of the brain (visual cortex). In many inherited retinal diseases (IRDs), genetic mutations cause photoreceptors to degenerate and die off, affecting an individual's ability to perceive light. However, while photoreceptors degenerate in IRDs, RGCs are preserved. They therefore represent a target cell to bypass degenerated photoreceptors, perceive light, and signal the brain. It has been shown KIO-301 selectively enters RGCs downstream of degenerated photoreceptors. In the presence of light, KIO-301 turns to an "on" position, triggering the RGC to signal the brain. In the absence of light, KIO-301 turns to an "off" position and signaling to the brain stops. In this way, the molecule acts as a light switch within the eye. In January of 2024, Kiora granted Théa Open Innovation (TOI), a sister company of the global ophthalmic specialty company Laboratoires Théa (Théa), exclusive worldwide development and commercialization rights, excluding Asia, to KIO-301 for the treatment of degenerative retinal diseases. As part of this agreement, the companies are jointly planning a Phase 2 multicenter, controlled clinical trial for retinitis pigmentosa. About Retinitis Pigmentosa Retinitis pigmentosa (RP) is a hereditary degenerative disorder affecting the retina's photoreceptors with no approved therapies. Typically characterized by progressive loss of side (peripheral) vision and night vision, it results from mutations in one or more than 150 genes. This disease affects approximately 1 in 4,000 individuals globally and about 100,000 patients in the United States alone. The prevalence, combined with the fact that 50% of patients are not qualified to drive by age 37 and are often considered legally blind by 55, underscores the need for treatment options. The condition's complexity and genetic heterogeneity make developing treatments challenging, underscoring the need for therapies that address as many or all of the gene mutations implicated in the disease. Kiora's development of KIO-301 as a mutation agnostic treatment for RP could meet this need. This drug is being developed as a standalone therapy or in combination with a potential future gene therapy. About Kiora Pharmaceuticals Kiora Pharmaceuticals is a clinical-stage biotechnology company developing and commercializing products for the treatment of orphan retinal diseases. KIO-301 is being developed for the treatment of retinitis pigmentosa, choroideremia, and Stargardt disease. It is a molecular photoswitch that has the potential to restore vision in patients with inherited and/or age-related retinal degeneration. KIO-104 is being developed for the treatment of posterior non-infectious uveitis. It is a next-generation, non-steroidal, immuno-modulatory, and small-molecule inhibitor of dihydroorotate dehydrogenase. In addition to news releases and SEC filings, we expect to post information on our website ( ) and social media accounts that could be relevant to investors. We encourage investors to follow us on Twitter and LinkedIn as well as to visit our website and/or subscribe to email alerts. Forward-Looking Statements Some of the statements in this press release are "forward-looking" and are made pursuant to the safe harbor provision of the Private Securities Litigation Reform Act of 1995. These "forward-looking" statements include statements relating to, among other things, the development and commercialization efforts and other regulatory or marketing approval efforts pertaining to Kiora's development-stage products, including KIO-301 and KIO-104, as well as the success thereof, with such approvals or success may not be obtained or achieved on a timely basis or at all, the ability of KIO-301 to improve visual function, the potential to expand KIO-301 to other indications including choroideremia and Stargardt disease, and the planned design of the Phase 2 clinical trial for KIO-301. These statements involve risks and uncertainties that may cause results to differ materially from the statements set forth in this press release, including, among other things, the ability to conduct clinical trials on a timely basis, the ability to obtain any required regulatory approvals, whether future trials of KIO-301 will yield similar results for participants, market and other conditions, and certain risk factors described under the heading "Risk Factors" contained in Kiora's Annual Report on Form 10-K filed with the SEC on March 23, 2023, or described in Kiora's other public filings. Kiora's results may also be affected by factors of which Kiora is not currently aware. The forward-looking statements in this press release speak only as of the date of this press release. Kiora expressly disclaims any obligation or undertaking to release publicly any updates or revisions to such statements to reflect any change in its expectations with regard thereto or any changes in the events, conditions, or circumstances on which any such statement is based, except as required by law. Contacts: Investors investors@kiorapharma.com Media kiora@crowepr.com Crowe PR To view the source version of this press release, please visit

Announces next-generation COVID-19 vaccine candidate as fourth respiratory vaccine to successfully meet its Phase 3 endpoints Expects two more Phase 3 readouts in 2024, including combination vaccine against flu and COVID-19, and vaccine against CMV Announces positive clinical trial data from three new vaccines against viruses that cause significant burden (Epstein-Barr virus, Varicella-Zoster virus, norovirus) and advances programs toward Phase 3 development Anticipates U.S. launch of vaccine against RSV following FDA approval and ACIP recommendation in 2024 Announces development and commercialization funding agreement with Blackstone Life Sciences for up to $750 million to advance flu program CAMBRIDGE, MA / ACCESSWIRE / March 27, 2024 / Moderna, Inc. (NASDAQ:MRNA) today announced at its fifth Vaccines Day event clinical and program updates demonstrating advancement and acceleration of its mRNA pipeline. The updates include data readouts in the Company's respiratory and latent and other vaccine portfolios, as well as commercial, manufacturing and financial announcements for its vaccines business. "Our mRNA platform continues a remarkable track record across our broad vaccine portfolio. Today, we are excited to share that four vaccines in our pipeline have achieved successful clinical readouts across our respiratory, latent and other virus franchises," said Stéphane Bancel, Chief Executive Officer of Moderna. "With five vaccines in Phase 3, and three more moving toward Phase 3, we have built a very large and diverse portfolio addressing significant unmet medical needs. We are focused on execution to further build momentum across our pipeline and business, and to deliver for patients who are impacted by these infectious diseases." Portfolio Overview The vaccine portfolio seeks to address infectious diseases that cause considerable health burdens and includes 28 vaccines addressing respiratory, latent and other pathogens. Latent and Other Vaccine Portfolio Moderna is advancing five vaccine candidates against viruses that cause latent infections, all of which are in clinical trials. When latent, a virus is present in the body but exists in a resting state, typically without causing any noticeable symptoms. Latent viruses can reactivate and cause clinical symptoms as a person ages, during times of stress or when immunity is compromised. The capacity for latency is a defining feature of members of the Herpesviridae family, including cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and Varicella-Zoster virus (VZV). Cytomegalovirus (CMV) CMV is the most common infectious cause of birth defects in the U.S. and is responsible for several billion dollars in annual healthcare costs. One in 200 babies in the U.S. are born with a congenital CMV infection, and of those affected, one in five will have severe, life-altering health problems. Possible short- and long-term sequelae of CMV infection include microcephaly, chorioretinitis, seizures, sensorineural hearing loss, cognitive impairment and cerebral palsy. There is currently no approved vaccine to prevent congenital CMV. CMVictory is a pivotal Phase 3 trial evaluating mRNA-1647 against primary CMV infection in women 16 to 40 years of age. The trial is a randomized, observer-blind, placebo-controlled study designed to evaluate the efficacy, safety and immunogenicity of mRNA-1647. The trial is fully enrolled with approximately 7,300 participants from 290 clinical sites globally. To date, 50 primary infection cases have accrued and are undergoing confirmation. The first interim analysis for the evaluation of vaccine efficacy, which will be triggered when both 81 confirmed per-protocol cases and 12 median months of safety follow-up have occurred, is expected as early as the end of 2024. Moderna's CMV vaccine candidate mRNA-1647 has advanced to indication expansion studies in adolescents 9 to 15 years of age and adult transplant patients, both of which have begun enrollment. Epstein-Barr virus (EBV) EBV is a major cause of infectious mononucleosis (IM) in the U.S., accounting for more than 90% of IM cases annually. Importantly, EBV and IM are associated with a higher lifetime risk of more serious sequelae including certain cancers such as gastric carcinoma, nasopharyngeal carcinoma and multiple types of lymphoma. The lifetime risk of developing multiple sclerosis (MS) is increased by 32-fold after EBV infection. There is currently no approved vaccine to prevent EBV. Moderna's EBV vaccine candidates are designed to tackle multiple EBV-associated conditions, including prevention of IM (mRNA-1189) and MS and post-transplant lymphoproliferative disorder, a subcategory of lymphoma in solid organ transplant patients (mRNA-1195). The Phase 1 trial for mRNA-1189 was designed to test the safety, reactogenicity and immunogenicity of four different dose levels in participants 12 to 30 years of age in the U.S. The randomized, observer-blind, placebo-controlled study showed mRNA-1189 was immunogenic and generally well tolerated across all dose levels. The Company is advancing mRNA-1189 toward a pivotal Phase 3 trial. The Phase 1 trial for mRNA-1195 was designed to test the safety, reactogenicity and immunogenicity of two drug products at four different dose levels in healthy EBV seropositive participants 18 to 55 years of age in the U.S. The randomized, observer-blind, placebo-controlled study is fully enrolled. Herpes simplex virus (HSV) Herpes simplex virus type 2 (HSV-2) infects approximately 13% of adults globally and is the primary cause of genital herpes. There are an estimated four billion people globally infected with HSV, of which 491 million cases are HSV-2. Recurrent genital herpes causes a reduction in quality of life, which antivirals (current standard of care) only partially restore. Moderna expects that if an HSV vaccine candidate could deliver similar efficacy as a suppressive antiviral treatment, compliance with recommended therapy and associated quality of life would improve. There is currently no approved vaccine to treat HSV-2. The first in human, fully enrolled Phase 1/2 trial of mRNA-1608 is designed to test safety and immunogenicity and to establish a proof-of-concept of clinical benefit in adults 18 to 55 years of age with recurrent HSV-2 genital herpes. The randomized 1:1:1:1, observer-blind, controlled study is fully enrolled with 300 participants in the U.S. Varicella-Zoster virus (VZV) Herpes zoster, also known as shingles, is caused by reactivation of latent VZV, the same virus that causes chickenpox. Declining immunity in older adults decreases immunity against VZV, allowing reactivation of the virus from latently infected neurons, causing painful and itchy lesions. Herpes Zoster occurs in one out of three adults in the U.S. in their lifetime and the incidence increases at 50 years of age. There is potential to reach a growing and underserved patient population. Moderna's VZV vaccine candidate mRNA-1468 has initial data available from a Phase 1/2 trial, which was designed to test safety and immunogenicity in healthy adults 50 years of age and older in the U.S. The randomized 1:1:1:1:1, observer-blind, active-controlled study of mRNA-1468 elicited strong antigen-specific T cell responses at one month after the second dose and was generally well tolerated. Results of the first interim analysis support the further clinical development of mRNA-1468 for the prevention of shingles. Additional results from the ongoing Phase 1/2 study will be available later this year, including persistence data. The Company is planning for a pivotal Phase 3 trial. Norovirus Enteric viruses, including norovirus, are a leading cause of diarrheal diseases, resulting in significant morbidity and mortality worldwide, particularly among young children and older adults. Norovirus is highly contagious and a leading cause of diarrheal disease globally, associated with 18% of all acute gastroenteritis (AGE), resulting in approximately 200,000 deaths per year and substantial healthcare costs. Given the wide diversity of norovirus genotypes, a broadly effective norovirus vaccine will require a multivalent vaccine design. There is currently no approved vaccine to prevent norovirus. The randomized, observer-blind, placebo-controlled Phase 1 trial was designed to evaluate the safety, reactogenicity and immunogenicity of trivalent (mRNA-1403) and pentavalent (mRNA-1405) norovirus vaccine candidates in 664 participants 18 to 49 years of age and 60 to 80 years of age in the U.S. An interim analysis showed that a single dose of mRNA-1403 elicited a robust immune response across all dose levels evaluated with a clinically acceptable reactogenicity and safety profile. The Company is advancing mRNA-1403 toward a pivotal Phase 3 trial. Respiratory Vaccine Portfolio Moderna's approach to ease the global burden of respiratory infections includes vaccine candidates against major causative pathogens, including SARS-CoV-2, respiratory syncytial virus (RSV) and influenza virus. Respiratory infections are a top cause of death in the U.S. and are particularly harmful to the young, immunocompromised, and older adults who experience more severe illness, greater incidence of hospitalization, and greater mortality than younger adults. Moderna's respiratory pipeline includes Phase 3 trials for investigational vaccines including a next-generation COVID-19 vaccine, an RSV vaccine, a flu vaccine, and a flu and COVID-19 combination vaccine. The pipeline includes three additional flu vaccine candidates with expanded antigen coverage as well as combination vaccine programs. COVID-19 Moderna continues to address the needs of the endemic COVID-19 market by focusing on public health efforts to increase vaccination coverage rates to reduce the substantial burden of COVID-19 as well as by advancing next-generation vaccines. The Company's mRNA platform can produce variant-matched vaccines on an accelerated time horizon, consistent with recent U.S. Food and Drug Administration (FDA) comments on the timing of potential strain selection for the fall booster season. A recent announcement of positive interim results from the NEXTCove Phase 3 trial showed that mRNA-1283 elicited a higher immune response against both the Omicron BA.4/BA.5 and original virus strains of SARS-CoV-2 compared to mRNA-1273.222, Moderna's licensed COVID-19 vaccine. mRNA-1283 is designed to be refrigerator-stable and paves the way for a combination vaccine against influenza and COVID-19, mRNA-1083, enhancing the Company's overall respiratory portfolio. This is Moderna's fourth infectious disease vaccine program with Phase 3 data. Respiratory Syncytial Virus (RSV) RSV is the leading cause of respiratory illness in young children, and older adults are at increased risk relative to younger adults for severe outcomes. In addition to acute mortality and morbidity, RSV infection is associated with long-term sequelae such as asthma and impaired lung function in pediatric populations, and exacerbation of chronic obstructive pulmonary disease in older adults. Annually, there are approximately two million medically attended RSV infections and 58,000 to 80,000 hospitalizations in children younger than five years old in the U.S. In the U.S., each year there are up to 160,000 hospitalizations and 10,000 deaths in adults 65 years and older due to RSV. Across high-income countries in 2019, RSV caused an estimated 5.2 million cases, 470,000 hospitalizations and 33,000 in-hospital deaths in adults 60 years and older. mRNA-1345 Moderna's RSV vaccine candidate, mRNA-1345, is in an ongoing Phase 2/3, randomized, observer-blind, placebo-controlled case-driven trial (ConquerRSV) in adults over 60 years of age. In this study, approximately 37,000 participants from 22 countries were randomized 1:1 to receive one dose of mRNA-1345 or placebo. Based on positive data from the ConquerRSV trial, Moderna has filed for regulatory approvals for mRNA-1345 for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and acute respiratory disease (ARD) in adults over 60 years of age. The trial met both its primary efficacy endpoints, with a vaccine efficacy (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p<0.0001) against RSV-LRTD as defined by two or more symptoms, and a VE of 82.4% (96.36% CI: 34.8%, 95.3%; p=0.0078) against RSV-LRTD defined by three or more symptoms. These data were published in the New England Journal of Medicine in December 2023. A subsequent analysis from the ConquerRSV study with a longer median follow-up duration of 8.6 months (versus 3.7 months in the primary analysis), with a range of 15 days to 530 days, and including subjects from the Northern and Southern Hemispheres was recently presented at the RSVVW'24 conference. In this supplemental analysis, mRNA-1345 maintained durable efficacy, with sustained VE of 63.3% (95.88% CI: 48.7%, 73.7%) against RSV-LRTD including two or more symptoms. VE was 74.6% (95% CI: 50.7%, 86.9%) against RSV-LRTD with ≥2 symptoms, including shortness of breath and 63.0% (95% CI: 37.3%, 78.2%) against RSV-LRTD including three of more symptoms. The stringent statistical criterion of the study, a lower bound on the 95% CI of >20%, continued to be met for both endpoints. mRNA-1345 has been granted Breakthrough Therapy designation by the FDA for the prevention of RSV-LRTD in adults over 60 years of age. The Company is awaiting regulatory approvals and the U.S. ACIP recommendation in 2024. Indication expansion studies for mRNA-1345 mRNA-1345 has the potential to protect all vulnerable populations from RSV. Moderna has initiated multiple Phase 3 expansion studies in adults over 50 years of age to evaluate co-administration and revaccination. Additional trials (Phase 1 - Phase 3) have been initiated for high-risk adults, as well as maternal and pediatric populations. Interim data from these studies could be available as early as 2024. Influenza (Flu) Worldwide, influenza leads to 3-5 million severe cases of flu and 290,000-650,000 flu-related respiratory deaths annually. Two main types of influenza viruses (A and B) cause seasonal flu epidemics, and the influenza A viruses lead to most flu-related hospitalization in older adults. The Company has several seasonal influenza vaccine candidates in clinical development. Moderna's seasonal flu vaccine, mRNA-1010, demonstrated consistently acceptable safety and tolerability across three Phase 3 trials. In the most recent Phase 3 trial (P303), which was designed to test the immunogenicity and safety of an optimized vaccine composition, mRNA-1010 met all immunogenicity primary endpoints, demonstrating higher antibody titers compared to a currently licensed standard-dose flu vaccine. In an older adult extension study of P303, mRNA-1010 is being studied against high dose Fluzone HD®; the trial is fully enrolled. The Company is in ongoing discussions with regulators and intends to 2024. Combination Respiratory Vaccines Moderna's combination vaccine candidates cover respiratory viruses associated with the largest disease burden in the category. The Phase 3 combination study of the Company's investigational combination vaccine against flu and COVID-19 (mRNA-1083) for adults aged 50 years and older is fully enrolled and data are expected in 2024. mRNA-1083 was granted Fast Track designation by the FDA in May 2023. Commercial Updates Respiratory viruses in addition to latent and other viruses represent large unmet or underserved medical needs, and the human and economic costs from these infectious diseases highlight the need for effective vaccines. To help address this need, Moderna expects multiple vaccine product launches in the next few years, each with significant addressable markets. The 2024 global endemic COVID-19 vaccine market alone is estimated by Moderna to be approximately $10 billion. COVID-19 continues to show a high burden of disease, and while COVID-19 hospitalizations remain high relative to RSV and flu, the risks of Long COVID are also becoming better understood. Moderna is focused on improving education and awareness to increase vaccination rates as Long COVID data suggests even traditionally low-risk groups should be vaccinated. Moderna is also working with health authorities to align the timing of COVID-19 and flu vaccine launches to help improve public health. For RSV, Moderna estimates the peak annual market to be approximately $10 billion. The Company expects a strong RSV vaccine launch into a large market in 2024. As the only mRNA investigational vaccine with positive Phase 3 data, Moderna's RSV vaccine candidate has a strong pro consistently strong efficacy across vulnerable and older populations, a well-established safety and tolerability profile, and ease of administration with a ready-to-use, pre-filled syringe formulation, which could relieve some of the burden that falls on pharmacies during the fall vaccination season. An interim analysis from an ongoing time and motion study evaluating differences in preparation time between a pre-filled syringe (PFS) presentation and vaccines that require reconstitution showed that a PFS presentation could relieve some of the burden that falls on pharmacies during the fall vaccination season. Results from this study suggest that pharmacies may be capable of preparing up to four times as many doses of PFS in an hour compared to vaccines requiring reconstitution. Moderna estimates flu vaccines represent an approximately $7 billion market in 2024. The market is expected to grow with the rise of more effective vaccines and there is an opportunity to expand the market with next-generation premium flu vaccines as well as combination respiratory vaccines, adding increased value to the health ecosystem. CMV is expected to be a $2-5 billion annual market. With no vaccine currently on the market and a potential vaccine launch in 2026, Moderna could be the first CMV vaccine in multi-billion-dollar latent vaccine market. In addition, EBV has the potential to address and reduce the burden and cost of EBV infection in multiple populations, while VZV provides the opportunity to enter a large and growing market, which could be $5-6 billion annually. The market for norovirus vaccines is similar to that of rotavirus in pediatrics with opportunity to expand into the adult population, and represents a $3-6 billion annual market. Moderna's vaccine portfolio targets large addressable markets, with an estimated total addressable market (TAM) of $52 billon for Moderna infectious disease vaccines, which includes a respiratory vaccines TAM of more than $27 billion and a latent and other vaccines TAM of more than $25 billion. Manufacturing The Company's manufacturing innovation supports expanding commercialization of a diverse pipeline through efficiency and productivity gains. Its mRNA manufacturing platform enables benefits such as quality, speed, scale and cost efficiency across a footprint that broadly includes the manufacture of plasmid, mRNA, lipid nanoparticles, as well as fill/finish and quality control capabilities. As the Company continues to build its footprint for the future, it is developing an agile global manufacturing network to meet commercial demand and support its growing pipeline. Pre-clinical through commercial manufacturing occurs at the Moderna Technology Center in Norwood, Massachusetts, which remains central to the Company's network. New facilities being constructed in Australia, Canada and the UK are expected to come online in 2025, and drug product capacity is achieved through a flexible contract manufacturing network. Additionally, the Company has purchased and started build-out of a manufacturing site in Marlborough, Massachusetts, to enable commercial scale of its individualized neoantigen therapy program. By continuing to pioneer new technologies, including advanced robotics, applying AI and other digital solutions, and driving network and capital efficiency, Moderna's manufacturing network is expected to also drive more predictable cost of sales. Research and Development Investment Strategy Today's updates provide further evidence that Moderna's mRNA technology platform is working, and with a rate of success higher than industry standard. Looking ahead, research and development will continue to be the Company's top capital allocation priority. As Moderna looks to create value through the research and development strategy for its vaccine portfolio, it is taking three prioritization parameters into consideration: pipeline advancement, revenue diversification and risk reduction. As part of its strategy, the funding options Moderna considers are self-funding, project financing and partnerships. Moderna recently entered into a development and commercialization funding agreement with Blackstone Life Sciences to advance the Company's flu program. As part of the agreement, Blackstone will fund up to $750 million with a return based on cumulative commercial milestones and low-single digit royalties. Moderna expects to recognize the funding as a reduction in research and development expenses and will retain full rights and control of the Company's flu program. This funding does not result in any change to Moderna's 2024 research and development framework of approximately $4.5 billion. About Moderna Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines. Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. INDICATION (U.S.) SPIKEVAX (COVID-19 Vaccine, mRNA) is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older. IMPORTANT SAFETY INFORMATION Do not administer to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine. Appropriate medical treatment to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of the vaccine. Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is higher among males under 40 years of age than among females and older males. The observed risk is highest in males 18 through 24 years of age. Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting. Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished response to the vaccine. The vaccine may not protect all vaccine recipients. Adverse reactions reported in clinical trials following administration of the vaccine include pain at the injection site, fatigue, headache, myalgia, arthralgia, chills, nausea/vomiting, axillary swelling/tenderness, fever, swelling at the injection site, and erythema at the injection site, and rash. The vaccination provider is responsible for mandatory reporting of certain adverse events to the Vaccine Adverse Event Reporting System (VAERS) online at or by calling 1-800-822-7967. Please see the SPIKEVAX Full Prescribing Information. For information regarding authorized emergency uses of the Moderna COVID-19 Vaccine, please see the EUA Fact Sheet. Spikevax® is a registered trademark of Moderna. Fluzone® is a registered trademark of Sanofi Pasteur. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the advancement of Moderna's programs under clinical development; the timing for anticipated approvals of vaccine candidates; the efficacy, safety and tolerability of vaccine candidates; the total addressable markets for programs under development; the efficiencies and advantages of Moderna's mRNA platform; future capital allocation and financing efforts; and anticipated spending for R&D in 2024. In some cases, forward-looking statements can be identified by terminology such as "will," "may," "should," "could," "expects," "intends," "plans," "aims," "anticipates," "believes," "estimates," "predicts," "potential," "continue," or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission (SEC), and in subsequent filings made by Moderna with the SEC, which are available on the SEC's website at . Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this presentation in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this press release. ​ ### Moderna Contacts Media: Chris Ridley Head, Global Media Relations +1 617-800-3651 Chris.Ridley@modernatx.com Investors: Lavina Talukdar Senior Vice President & Head of Investor Relations +1 617-209-5834 Lavina.Talukdar@modernatx.com SOURCE: Moderna, Inc. View the original press release on accesswire.com