CN1084391A - 表面改良的抗癌纳颗粒 - Google Patents

表面改良的抗癌纳颗粒 Download PDF

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CN1084391A
CN1084391A CN93108050A CN93108050A CN1084391A CN 1084391 A CN1084391 A CN 1084391A CN 93108050 A CN93108050 A CN 93108050A CN 93108050 A CN93108050 A CN 93108050A CN 1084391 A CN1084391 A CN 1084391A
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anticarcinogen
granule
surface modifier
described surface
phentriazine
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CN1063630C (zh
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P·P·萨波达
E·利弗西治
G·G·利弗西治
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Abstract

本发明公开了主要由结晶抗癌剂组成的分散性 颗粒，其表面吸附有足够量的表面改良剂以维持有效 平均粒度小于约1000nm。含有该种颗粒的抗癌组 合物表现出毒性减低和/或疗效增强，并可以通过注 射途径给药。

Description

本发明涉及颗粒形式的抗癌剂、含有此种颗粒的抗癌组合物和应用该颗粒的方法。
治疗指数是一种衡量一种药物产生期望效果的选择性大小的指标，其定义是半数致死量与半数有效量之比值，即（LD50/ED50）见（Goodman and Gilman，The Pharmacological （Basis of Therapeutics，Eight edition，P68-69）。几乎所有的抗癌剂都具有低治疗指数，例如小于1.0。提高治疗指数，例如通过减低毒性或增强疗效，就能使医生在用抗癌剂治疗癌症病人时有更多的选择性。因此，减低毒性和/或增强疗效并由此提高抗癌药治疗指数的方法对治疗癌症将具有重要价值。
另外，一些微溶于水的药物，例如微溶于水的抗癌剂，不容易制备成可经静脉快速浓注的剂型。将微溶于水的药物做成注射剂型是一个棘手的问题。如果能把微溶于水的药物，如把微溶于水的抗癌剂做成静脉快速浓注剂型将是非常理想的。
我们发现含有抗癌剂的抗癌组合物以表面改良的纳颗粒（nanoparticle）形式表现出毒性降低和/或疗效增强。
更加具体的是，按照本发明，能提供主要含有结晶抗癌剂的颗粒，其表面吸附着表面改良剂，该改良剂的量能足以维持颗粒的有效平均粒径小于约1000nm。
本发明还进一步提供含上述颗粒的抗癌组合物。
在本发明的另一实例中，提供了一种治疗哺乳动物的方法，该方法包括将所述抗癌组合物给予哺乳动物。
在本发明再一实例中，提供了一种对抗癌剂增强疗效和/或减低毒性的方法，该方法包括将药剂以上述颗粒形式给药的步骤。
本发明的一个特点是提供了毒性降低的抗癌组合物。
本发明的另一特点是提供了疗效增强的抗癌组合物。
本发明的再一特点是提供了将一些微溶于水的抗癌剂能以静脉快速浓注方式给药的组合物。
本发明的再一特点是提供了将微溶于水的抗癌剂静脉快速浓注后呈现延长血液池循环的组合物。
本发明，部分是根据表面改良的抗癌剂纳颗粒具有毒性减低和/或疗效增强的发现。尽管本文主要描述了本发明用于优选的药物类型，即包括免疫抑制剂在内的抗癌剂，但是它也可应用于其它类型的低水溶性药物，尤其是那些治疗指数低的药物。
本发明的颗粒包含抗癌剂。抗癌剂以一种或多种独立的结晶相形式存在。结晶相与无定形相，即常规的溶剂沉淀法制备的大小在亚微米范围的非结晶颗粒不同，如在美国专利4，826，689号中所述。
本发明可被应用于很多种类的抗癌剂。但所述抗癌剂必须是微溶的而且至少在一种液体介质中是可分散的。所谓“微溶”是指在操作温度（如室温）下，药物在液体分散介质（如水）中的溶解度小于约10mg/ml，最好小于1mg/ml。优选的液体分散介质是水。但是，本发明也可以使用抗癌剂能在其中分散的其它液体介质，它们包括：例如盐水溶液、红花油、溶剂类（如乙醇、叔丁醇、已烷、和甘油）。水分散介质的pH值可以用本领域已知的方法调节。
抗癌剂最好选自烷化剂、抗代谢剂、天然产物、激素和拮抗剂及其它药剂（如辐射致敏剂）。
烷化剂的例子包括具有双-（2-氯乙基）-胺基团的烷化剂如：氮芥、苯丁酸氮芥、苯丙氨酸氮芥、尿嘧啶氮芥、甘露醇氮芥、超磷氮芥、氧氮芥、环磷酰胺、异环磷酰胺、三磷酸酰胺;
具有取代的氮丙啶基团的烷化剂，如三亚胺嗪、噻替哌、三亚胺醌和丝裂霉素;
磺酸烷基酯类的烷化剂，如白消安，哌酰硫烷和哌酰硫胺（piposulfam）;
烷化的N-烷基-N-亚硝基脲衍生物，如卡氮芥、罗氮芥、赛氮芥或链脲霉素;和二溴甘露醇、氮烯唑胺和甲基苄胼类的烷化剂。
抗代谢剂的例子包括叶酸类似物，如氨甲喋呤;
嘧啶类似物，如氟尿嘧啶、氟尿核苷、喃氟啶、阿糖胞苷、碘苷、氟胞嘧啶;
嘌呤衍生物，如巯基嘌呤、6-巯基鸟嘌呤、硫唑嘌呤、硫咪嘌呤、阿糖腺苷、戊咪二氮
Figure 931080509_IMG1
和嘌呤毒素。
天然产物的例子包括长春花属生物碱，如长春碱和长春新碱;
表鬼臼毒素类，如鬼臼乙叉甙和鬼臼噻吩甙;
抗生素类，如阿霉素、正定霉素、doctinomycin、柔红霉素、亚德里亚霉素、光辉素、博来霉素和丝裂霉素;
酶类，如L-天冬酰胺酶;
生物反应调节剂类，如α-干扰素;
喜树碱;
紫杉酚;和
类视黄醇类如视黄酸。
激素和拮抗剂的例子包括肾上腺皮质类固醇类，如强的松;
孕酮类，如己酸17-羟孕酮，62-甲-17-羟孕酮乙酸酯和甲地羟孕酮乙酸酯;
雌激素类，如己烯雌酚和乙炔基雌二醇;
抗雌激素类，如它莫西芬;
雄性激素类，如睾丸酮丙酸酯和氟羟甲基睾酮;
抗雄性激素类，如氟硝西酰胺;和
促性腺激素释放激素类似物，如亮丙瑞林。
其它药剂的例子包括辐射致敏剂类，如1，2，4-苯并三嗪-3-胺1，4-二氧化物（SR        4889）和1，2，4-苯并三嗪-7-胺1，4-二氧化物（WIN        59075）;
铂配位络合物，如顺氯氨铂和碳铂;
蒽二酮类，如米托蒽醌;
取代的脲类，如羟基脲;和
肾上腺皮质抑制剂类，如邻对滴滴滴和氨鲁米特。
另外，抗癌剂可以是免疫抑制剂，如环孢霉素、硫咪嘌呤、柳氮磺胺吡啶、甲氧呋豆素和酞咪哌啶酮。
能够应用于本发明的抗癌剂是已知化合物和/或能用本专业已知方法制备。
所述抗癌剂可以单独，或与一种或多种抗癌剂联合应用。
本发明的颗粒含有上述抗癌剂，其表面吸附有表面改良剂。据信适用的表面改良剂是那些通过物理作用吸附在抗癌剂的表面但不与抗癌剂形成化学结合的物质。
合适的表面改良剂最好选自已知的有机和无机药物赋形剂。这类赋形剂包括各种多聚物、低分子量寡聚物、天然产品和表面活性剂。优选的表面改良剂包括非离子型和阴离子型表面活性剂。赋形剂的典型例子包括：明胶、酪蛋白、卵磷酯（磷酯类）、阿拉伯胶、胆固醇、西黄蓍胶、硬脂酸、氯化苄烷铵、硬脂酸钙、单硬脂酸甘油酯、十八醇十六醇混合物、聚乙二醇1000单醋醚乳化蜡、脱水山梨糖醇酯、聚氧乙烯烷基醚（如聚乙二醇醚中的聚乙二醇1000单醋醚）、聚氧乙烯蓖麻油衍生物、聚氧乙烯脱水山梨糖醇脂肪酸酯[如市售品吐温（TweenTM）]、聚乙二醇、硬脂酸聚氧乙烯、胶体二氧化硅、磷酸盐、十二烷基硫酸钠、羧甲基纤维素钙、羧甲基纤维素钠、甲基纤维素、羟乙基纤维素、羟丙基纤维素、羟丙甲基纤维素酞酸酯、非结晶纤维素、硅酸铝镁、三乙醇胺、聚乙烯醇（PVA）、聚乙烯吡咯烷酮（PVP）。这些赋形剂的多数在Handbook of Pharmaceutical Excipients中有详细描述，该书由美国制药协会和大不列颠制药会联合出版，制药出版社，1986。表面改良剂可以买到市售品或/和用本专业已知方法制备。可以同时用两种或两种以上的表面改良剂。
尤其优选的表面改良剂包括聚乙烯吡咯烷酮、四丁酚醛、Polaxomer类（如PluronicTMF68，F108和F127，它们是能从BASF购得的环氧乙烷和环氧丙烷的嵌段共聚物）、和Poloxamine类（如TetronicTM908（T908），它是一种四功能嵌段共聚物，其制备是把环氧乙烷和环氧丙烷按顺序加到从BASF购得的乙二胺中）、葡聚糖、卵磷酯、气溶胶OTTM（AOT）（它是能从American Cyanamid公司得到的磺化琥珀酸钠二辛酯）、DuponolTMX-200（它是能从Rohm和Haas公司得到的烷基芳基聚醚磺酸盐）、吐温20、40、60和80（可从ICI Speciality Chemicals公司得到，它们是聚氧乙烯脱水山梨糖醇脂肪酸酯）、司班（Span）20、40、60和80（是脱水山梨糖醇脂肪酸酯类）、Arlacel 20、40、60和80（是脱水山梨糖醇脂肪酸酯，可从Hercules Inc.公司得到）、CarbowaxTM3550和934（是能从Union Carbide得到的聚乙二醇）、CrodestaTMF-110（是能从Croda Inc.公司得到的蔗糖硬脂酸酯和蔗糖二硬脂酸酯的混合物）、Crodesta SL-40（能从Croda Inc.公司得到）、氯化十六基三甲胺（CTAC）、牛血清白蛋白和SA90HCO，后者是C18H37CH2（CON（CH3）CH2-（CHOH）4CH2OH）2。已经发现的特别有用的表面改良剂包括聚乙烯吡咯烷酮、Pluronic F-108、聚乙烯醇和阿拉伯胶。
表面改良剂被吸附在抗癌剂表面，其量应足以维持有效平均颗粒的粒度小于约100nm。表面改良剂不与抗癌剂或其自身发生化学反应。而且，每个被吸附的表面改良剂分子基本上不发生分子间的交联。
本文所用“颗粒粒度”是指用本专业人员熟知的常规测定颗粒大小的方法测得的平均颗粒粒度数值，如沉降场流分级法、光子关联能谱法或盘式离心法。所谓“小于1000nm”的有效平均颗粒粒度是指用上述方法测得至少有90%的颗粒的平均颗粒粒度小于约1000nm。在本发明特别优选的实例中，有效平均颗粒粒度小于约400nm。在本发明的有些实例中，有效平均颗粒粒度小于约300nm。关于有效平均颗粒粒度，优选至少95%，更优选至少99%的颗粒粒度小于有效平均值，如1000nm。在特别优选的实例中，基本上所有颗粒的粒度都小于1000nm。
Motoyama等人，在美国专利4，540，602号中公布了在一种水溶性高分子物质的水溶液中研磨一种固体药物的方法，这种湿磨法的结果是使药物形成了很细的直径从小于或等于0.5μm至5μm的微小颗粒。但是，未提及能得到平均粒度小于1μm的颗粒。尝试重复Motoyama等人所述的湿磨法得到的颗粒的平均粒度明显大于1μm。
本发明的颗粒可以用下法制备：将抗癌剂分散于液体分散介质中，并在研磨介质存在下用机械手段将抗癌剂的颗粒减小至有效平均粒度小于约1000nm。颗粒可以在有表面改良剂存在下被磨细。此外颗粒磨细后可以与表面改良剂接触。
下面将阐述制备本发明的颗粒的一般方法。所选抗癌剂是购买的和/或用本专业已知方法制备的惯用粗品。所选粗品抗癌剂的粒度用筛检法测量、最好（但不是必须）小于约100μm。如果抗癌剂粗颗粒的粒度大于约100μm，那么最好用常规的磨细方法如空气喷射磨或破碎磨将其粒度减小至100μm以下。
然后，可以把所选粗抗癌剂加入对它基本上不溶解的液体介质中，形成初混物。抗癌剂在液体介质中的浓度为0.1～60%，优选5%至30%（W/W）。最好表面改良剂存在于初混物中，但非必须如此。表面改良剂的浓度按药物和其本身的总重计为约0.1-90%，优选的为1-75%，更优选的为20-60%。初混物混悬液的表观粘度最好小于约1000厘泊。
初混物可以直接用机械手段将其平均粒度在分散相中减小至1000nm以下。当用球磨机研磨时最好直接应用初混物。另一种方法，将抗癌剂和任意的表面改良剂，用适当的混合方法分散在液体介质中，如用辊筒式磨或Cowles型混合器，直到形成肉眼观察不到大团块的均匀的分散体系为止。如果用循环式介质磨研磨时最好将初混物经过此预磨分散步骤。
用于减小抗癌剂颗粒粒度惯用的机械手段可以采用分散磨形式。适宜的分散磨包括球磨机、擦碎机、振动磨、行星磨、介质磨（如砂磨机和珠磨机）。最好采用介质磨，原因是它能在相对短的时间产生预期结果，即希望的颗粒粒度。就介质磨而言，初混物的表观粘度最好在约100-1000厘泊范围内。对于球磨机粉碎，初混物的表观粘度最好在大约1-100厘泊的范围内。这样的粘度范围能在有效的颗粒破碎和介质损耗之间得到最佳平衡。
用于研磨颗粒步骤的研磨介质可以选自刚性介质，优选球形或颗粒状，其平均粒度小于约3mm，更好的小于约1mm。这种介质具有较短的加工时间和对研磨设备的磨损较轻，同时能提供本发明的颗粒。研磨介质的原料选择并不重要。但是，氧化锆，如以镁稳定的95% ZrO、硅酸锆、玻璃研磨介质能提供污染物含量在制备药用络合物所允许的范围内的颗粒。再者，其它介质如不锈钢、二氧化钛、氧化铝、钇稳定的95% ZrO也能应用。优选介质的比重要大于2.5g/cm3。
研磨的时间变化很大，主要取决于特定的机械方法和加工条件。对于球磨机，加工时间可以需要五天或更长。另一方面，用高剪切介质磨小于一天的加工时间（保留时间从一分钟至几个小时）已提供了期望的结果。
粉碎颗粒的过程必须在对抗癌剂无明显降解的温度下进行。通常优选在低于30-40℃的温度下加工。如果需要，加工设备可以用常规冷却设备冷却。本发明方法在室温和加工压力条件下进行，所述条件对研磨方法是安全的和有效的。例如，球磨、擦磨和振动磨一般在常压下加工。介质磨的操作压力一般约为20psi（1.4kg/cm2）。
如果没有在初混物中加表面改良剂，则必须在研磨后向分散体系中加入上述数量的表面改良剂。然后，可以混合分散体系，例如剧烈振摇。另一种选择，可以用声处理步骤，如用一种超声源。比如，可以将分散体系用20-80KHz的超声波能处理1-120秒钟。
抗癌剂和表面改良剂的相对量变化范围很大，表面改良剂的适宜用量取决于，诸如所选的具体的抗癌剂和表面改良剂、表面改良剂的临界乳化浓度（形成乳化微粒时）、抗癌剂的表面积等。优选的表面改良剂的用量为每平方米抗癌剂表面积用0.1-10mg左右。以干颗粒的总重量计，表面改良剂的用量可为0.1-90%，优选为0.5-80%，更优选为1-60%。
已发展了一种简单的筛选方法，通过该方法可以选择到能相互兼容的抗癌剂和表面改良剂，因而提供了理想颗粒的稳定的分散体系。首先，将抗癌剂的粗颗粒被分散到一种液体中，如水中（2%，W/V），抗癌剂在该液体中是基本不溶的，并在下列条件下用滚筒式研磨120小时。
研磨的容器：8盎司（250ml）玻璃罐，
研磨容器的可利用体积：250ml
介质体积：120ml
介质种类：预清洗过的1.0mm的氧化锆珠（从Zircoa，Inc.得到）
研磨时间：120小时
浆体积：60ml
每分转数：92
室温
用常规方法把浆液与研磨介质相分离，如把浆液倒出研磨容器或用吸管将浆液吸出。将分离后的浆液分成若干分，并加入占抗癌剂和表面改良剂总重2-50%的表面改良剂。然后把分散系用声处理（一分钟，20KHz），或用多管旋蜗混合器处理一分钟，使团块分散，然后用光子关联能谱仪（PCS）和/或光学显微镜（放大1000倍）下进行粒度分析。如果观察到稳定的分散体系时，那么就可以按照上述优化制备该抗癌剂与该表面改良剂相组合的方法。所谓“稳定的”是指制备后的分散物无肉眼可见的絮状物或颗粒团聚物，制备之后最好在1000倍光镜下观察15分钟，甚至至少观察两天或更长时间。另外，优选的颗粒当分散于0.1N盐酸和/或磷酸盐缓冲生理盐水（pH7.4PBS）中或大鼠血浆中时不形成絮状物或结聚物。
形成的分散体系是稳定的，它由液体分散介质和上述颗粒组成。表面改良的抗癌剂纳颗粒分散体系可以用本专业已知的技术用流化床喷涂器喷涂于蔗糖颗粒或药物赋形剂上。
依照本发明的抗癌药剂组合物包括上述的颗粒和为此而应用的药学上可接受的载体。适宜的药学上可接受的载体是本专业技术人员熟知的。这些载体包括生理学允许的无毒载体、供非肠道注射、以液体或固体形式口服、直肠给药、鼻腔给药、肌内给药、皮下给药等等的辅剂或载体。
按照本发明，治疗哺乳动物的方法包括给需要治疗的动物有效数量的上述抗癌剂组合物这一步骤。治疗用抗癌剂的剂量水平的选择是对具体组合物和给药方式能获得期望的有效治疗反应的量。本专业技术人员可以很容易地确定所选剂量，它主要取决于具体的抗癌剂、期望疗效、给药途径、期望疗程和其它因素。
正如下列实施例所显示，本发明抗癌组合物的一个尤其重要的特征是显示毒性减低和/或疗效增强。况且，本发明的颗粒表现出在血液池的循环时间延长。
再有，在此以前抗癌剂是不能注射给药的，当按照本发明制备成纳颗粒并配制成抗癌组合物后，可以非常有效地注射给药，比如用静脉快速浓注。
下列实施例进一步阐明本发明。
实施例1-4纳颗粒化的哌酰硫烷
实施例1
将哌酰硫烷（购自Eastman        Kodak）于0.33%的聚氧乙烯脱水山梨糖醇单油酸酯即吐温80（ICI        Americas，Inc.，Wilmington，DE）和0.67%脱水山梨糖醇单油酸酯即Span        80（ICI）的混合物中，用1mm的氧化锆珠磨大约96小时，得到直径大约为240nm的颗粒。最后哌酰硫烷在混悬物中的浓度是10mg/ml。颗粒在大鼠血浆中对絮状沉淀/聚集作用是稳定的。
研磨条件：哌酰硫烷粗混悬液的制备如下：把300mg的该药加入事先盛有60ml预洗过的1mm氧化锆珠（Zircoa        Inc.，Solon，OH）和30ml        1%的Tween        80/S        pan        80（1∶2比例）溶液的4盎司（120ml）棕色瓶中。表面活性剂溶液的制备是通过准确称量333mg        Tween        80和667mg        Span        80，并放入容量瓶中，然后加入消毒的注射用水以溶解/分解表面活性剂。用足量的水把最后体积调至100ml。氧化锆珠首先用1N硫酸清洗、然后用去离子水洗几次。介质在100℃真空干燥器中过夜干燥。
封口的原级容器被装入次级夹层铝保护罐中，牢固固定。在滚筒式磨上（US        Stoneware，Mawah，        NJ）以144转/分的速度磨96小时。研磨结束后把浆液与研磨介质分离，并用PCS（光子关联能谱）测定颗粒大小。用放大倍数为1000的光学显微镜对颗粒在大鼠血浆中的稳定性进行评价。制剂的最终pH值是6。
对照A（未磨）;将40mg粗哌酰硫烷分散在含3%乙醇和1%Tween        80的水中以形成粗混悬液。该混悬液不能静脉注射。
用雌性小鼠（平均体重22克）对实施例一的疗效进行了评价，小鼠在第0天接种早期乳腺腺癌＃16/C。从第1天开始连续注射几天的该制剂。抗癌活性是用检查肿瘤重量并与对照组动物进行比较来评价的。下面是结果：
治疗        给药途径*        总剂量        体重减轻%        T/C        杀伤细胞
(mg/kg)        %        对数Log10
对照        ----        ---        +5.5        ---        ----
实施例1        IV        356        -5.5        0        2.75
(243nm)        IV        220        -5.5        2        2.75
IV        137        -1.8        2        2.25
IV        85        0        18        1.0
对照    A        SC        800        -10.8        0        2.1
＊给药方式：IV-静脉;SC-皮下
实施例一的制剂作为10mg/ml的悬液可直接注射。在78mg/kg的单次剂量注射后没有急性中毒症状。
T/C＝治疗组动物的肿瘤重量除以对照组动物的肿瘤重量，以百分数表示。低数值表示高疗效。0%说明治愈。＜10%认为是高活性，10-42%认为是中等活性，＞42%认为无活性。
杀伤对数＝（T-C）/3.22（Td），T是治疗组动物的中位数肿瘤长到1000mg的天数，C是对照组动物的中位数肿瘤长到1000mg的天数，Td是肿瘤体积增加一倍的天数。治愈的（无肿瘤动物）被剔除不予计算（T-C）。
与以往的组合物相比，实施例一中本发明的组合物表现出毒性减低和疗效增强，且可以静脉快速浓注给药。
实施例2-4
重复实施例1中所述的研磨操作只是将Tween        80与Span        80的比例变成2∶1。所得颗粒的平均粒度是297nm。
重复实施例1中所述的研磨操作只是将Tween        80与Span        80的比例变为1∶1。所得颗粒的平均粒度是380nm。
重复实施例1的研磨操作只是表面改良剂换为1∶1的Tween        60和Span        60。所得颗粒的平均粒度是301nm。
用牛血清白蛋白作表面改良剂也制得了稳定的哌酰硫烷纳颗粒。
实例5-7纳颗粒化的喜树碱
实施例5
把约60ml预洗过的氧化锆珠（1mm）放入120毫升的圆形棕色广口瓶中，向其中加入0.35克的Tetronic        908（BASF）和0.35克的喜树碱（西格马化学公司纯度为95%）。向上述混合物中加35ml注射用水（Abbott）。将瓶口封好并装到滚筒式磨上。在100转/分下施转该瓶7天完成研磨。
在研磨结束后，取一份（100μl）的样用Malvern        Zetasizer检测粒度。检测结果为颗粒的平均粒度是240nm。
实施例6
重复实施例5，只是用聚乙烯醇（分子量3-7万）代替Tetronic        908。最后颗粒粒度是256nm。
实施例7
重复实施例5，只是用阿拉伯胶代替Tetronic        908。最后的颗粒粒度是298nm。
用两种鼠瘤，即乳腺原癌＃16/C和胰腺导管腺癌＃03对纳颗粒化的喜树碱制剂的疗效进行了评价。抗癌活性是用测定实验动物和对照动物的瘤重来评价的。
1.对胰腺导管腺癌＃3疗效的研究
实施例        给药途径        剂量        体重%        药物        T/C
mg/kg        下降        致死        %
对照B        SC        60        -24.1        6/6        -
SC        40.2        -21.8        5/5        -
SC        26.7        -18.2        5/5        -
SC        18        -10.9        1/5        62
6        IV        83.1        -16.7        1/4        14
IV        78.2        -14.6        1/4        55
IV        48.6        -8.3        0/4        0
IV        24.3        -4.2        0/4        18
PVA
对照        IV        ----        +6.3        0/4        100
7        IV        93.5        -16.7        1/4        7
IV        46.8        -14.6        0/4        17
IV        23.4        -8.3        0/4        11
阿拉伯胶        IV        ----        0.0        0/4        60
对照
对照B制剂由在3%的乙醇和1%的吐温20（Tween 20）中含有1%的粗喜树碱组成。对照B只能经皮下给药，且即使在最低皮下给药的剂量（18mg/kg）也无活性。对照B使 1/5 的受试动物中毒。相反，本发明纳颗粒化的喜树碱制剂的剂量范围在24-93mg/kg是用静脉给药的，并安全而有效。
2.用乳腺腺癌＃16/C鼠癌模型研究药效
实施例        给药途径        剂量        体重%        药物        T/C
mg/kg        减轻        致死        %
对照    B        SC        60        -23.5        5/5        -
SC        30        -20.9        5/5        -
SC 15 -18.3 3/5 14**
5        IV        65        -17.4        0/5        23
IV        33        -18.7        1/5        33
IV        16        -2.2        0/5        63
T908        IV        --        +4.3        0/2        100
对照
6        IV        65        -21.7        5/5        -
IV        33        -15.7        0/5        100
阿拉伯胶        IV        --        +4.3        0/2        100
对照
T908和PVA对照分别是含有1%的该两种表面改良剂的水溶液。对照B是经皮下注射的，且所试各剂量都有毒性。本发明的纳颗粒化喜树碱的制剂的有效剂量是从静脉给药的。
＊＊        %T/C在对照组是以存活的动物来计算的，动物数为2。
3.血液和肿瘤中的清除
为了确定疗效增强是否伴随有药代动力学性质的改变，用乳腺腺癌＃16/C鼠癌模型研究了血液清除和肿瘤中的分布。
用10mg/ml按实施例5和实施例6制剂的喜树碱从尾静脉给带瘤小鼠注射，对照组用以0.1N        NaOH溶解的5mg/ml的喜树碱溶液。在注射后的不同时间，即5分、30分、60分、2小时、4小时、8小时、16小时、24小时和48小时，把动物无痛苦处死后，收集血样并将肿瘤取出。药物含量用高效液相色谱测定（HPLC）。结果显示，本发明的组合物影响药物在血液循环池和肿瘤中的清除。
血液和肿瘤中的半衰期
制剂        血液        肿瘤
实施例6        18小时        >48小时
实施例5        13小时        >48小时
对照        1.6小时        13.5小时
当按照本发明进行制剂时，喜树碱的清除半衰期和在癌瘤中的存留时间明显延长。得出的结论是喜树碱纳颗粒制剂的药代动力学指标直接与药效改进有关。
实施例8-10纳颗粒化的鬼臼乙叉甙
实施例8
重复实施例5，只是用1.7克的鬼臼乙叉甙与1.7克的聚乙烯醇（PVA）相组合，而且研磨时间是14天。最终颗粒粒度是310nm。颗粒在酸和血浆中是稳定的。
实施例9
重复实施例8，只是用Pluronic        F-108（BASF）替代聚乙烯醇。最终颗粒粒茺是312nm。颗粒在酸和血浆中稳定。
实施例10
在灭菌水中把（2%）鬼臼乙叉甙研磨7天。将研磨过的浆液用2%的Pluronic        F127配成1∶1的混合液。在测定颗粒大小前用旋蜗混合器搅匀混合液。最终颗粒粒度是277nm。浆液在模拟胃液、PBS（pH7.4）（磷酸盐缓冲生理盐水）和鼠血浆中是稳定的。
效用研究
用胰腺导管腺癌＃03（PANC＃03）对纳颗粒化鬼臼乙叉甙制剂进行了两项独立的评价研究。对照C是用按照第46版的Physicians[′Desk Reference第741-743页中所述配方制备的2%鬼臼乙叉甙的非水溶液。如上所述，抗癌活性是通过测量试验动物和对照动物的瘤重进行评价的。这些研究证实了本发明的鬼臼乙叉甙组合物提供了一种应用高剂量药物而无严重毒性反应的方法。
1.用鼠癌瘤模型PANC＃03行的纳颗粒化的鬼臼乙叉甙的效用研究
实施例        途径        剂量        体重%        药物        T/C
mg/kg        减轻        致死        %
对照    C        IV        120        -24.0        0/5        4.0
IV        75        -4.0        0/5        20.0
7        IV        160        -12.0        0/5        18.0
IV        100        0.0        0/5        32.0
IV        62        2.0        0/5        42.0
8        IV        160        -12.0        0/5        26.0
IV        100        +2.0        0/5        35.0
IV        62        +4.0        0/5        35.0
9        IV        170        -18.5        1/5        16
IV        85        -2.0        0/5        35
IV        43        +2.5        0/5        41
实施例11-16纳颗粒化的紫杉酚
实施例11
将约18ml预清洗的氧化锆研磨介质（1mm）加入一个30ml的棕色罐中。向其中加入240mg的紫杉酚（西格马化学公司）和180mg的吐温20。最后向罐内加12ml注射用水。将罐口封好并装到滚筒式磨上研磨11天。最后，颗粒粒度是327nm。该制剂对PBS（pH7.4）和大鼠血浆是稳定的。
实施例12
重复实施例11，但是用聚乙烯醇（PVA，分子量在3-7万）代替Tween        20。颗粒粒度最后为365nm。
用带早期乳腺腺癌＃16/C的小鼠对以上样品进行了效用研究。抗癌活性是用比较紫杉酚治疗动物的瘤重与未治疗动物的瘤重的方法进行评估的。毒性是用以体重减轻和死亡为两端点之间的剂量范围进行评估的。所有样品都是静脉注射给药。
实施例        剂量        %体重        死亡        第11天的        T/C
mg/kg        减轻        平均瘤重        %
对照    D        ----        +6.1        ++++        1539mg        --
实施例11        108.5        -1.5        0/5        1528        13
实施例12        108.5        -3.0        0/5        201        99
得不到紫杉酚的对照样品。但是，以Cremophore        EL配制的紫杉酚以25mg/kg的总剂量一次用药立刻使动物死亡。但是，用本发明的组合物配制的紫杉酚一次以88mg/kg的剂量注射也没有明显的不良效果。
用几种表面改良剂对以类似实施例11的方法制备的悬浮液进行处理。加入新的表面改良剂后对混合物进行旋蜗混匀并评价其颗粒大小和液体的稳定性。所有悬浮液都含有1%的紫杉酚和0.75%的吐温20。结果如下：
实施例        表面        液体稳定性
改良剂        浓度%        粒度(nm)        PBS        大鼠血浆
13        CTAC        0.25        364        OK        絮状作用
14 AOT 0.25 322 SA*SA
15        F68        0.5        297        SA/OK        SA/OK
16        T908        0.5        313        SA/OK        SA/OK
＊SA＝轻度聚集
OK＝良好
实施例17-18纳颗粒化的WIN59075
将约60ml预洗过的氧化锆（1mm）研磨介质加入到一棕色罐中。然后加入1.5克WIN59075和28.5ml的注射用水。将罐品封好并装在滚筒式磨上以95转/分的速度磨48小时。用光子关联能谱法测定的颗粒粒度是322nm，但是显示有比较大的颗粒存在。又继续磨了5天。
取0.5ml用上述方法制备的WIN59075浆液与0.5ml        6%的表面改良剂液混合后进行研究。药物的最终浓度是2.5%，而表面改良剂的最终浓度是3%。将用表面改良剂稳定的WIN59075纳颗粒悬液用PBS（pH7.0）或1.0N盐酸（pH1）进行处理。用光学显微镜观察法测定液体稳定性。结果如下：
实施例        表面        稳定性        人血浆
改良剂        pH1        pH7
17        PVP(12K)        好        好        好
(BASF)
18        阿拉伯胶        ---        SA/OK        SA/OK
(Aldrich)
结论是可以制备稳定的WIN59075纳颗粒。
实施例19-22        SR4889纳颗粒
将7.5ml预洗过的氧化锆介质（1mm）连同18.75mg        SR4889和3.75ml水一齐加入15ml的琥珀色瓶中。磨11天后将介质与纳颗粒悬浮液分离。向每份为100μl的悬浮液中加入100μl        2%表面活性剂溶液，最后药物浓度为0.25%，表面活性剂浓度是1%。将混合物混匀后进行粒度测定。将10μl升悬浮液与90μl大鼠血浆混合后用光学显微镜评价液体稳定性。结果如下：
液体稳定性
实施例        表面改良剂        粒度(nm)        鼠血浆
19        PVP(12K)        134        良好
20        阿拉伯胶        344        SA/OK
21        吐温80        128        良好
22        T908        130        凝聚
实施例23纳颗粒化的视黄酸
将30ml预洗过的氧化锆介质加入60ml的琥珀色瓶中。向其中加入1g反式视黄酸（Sigma）、470mg四丁酚醛和15ml水。把混合物在滚筒式磨上磨15天。最终粒度是140nm。当与大鼠血浆或模拟胃液接触时该纳颗粒悬浮液是稳定的。

Claims (27)

1、主要由结晶抗癌剂组成的颗粒，其表面吸附有足够量的能维持平均有效粒度小于约1000nm的表面改良剂。
2、权利要求1的颗粒，其平均有效粒度小于400nm。
3、权利要求1的颗粒，其平均有效粒度小于300nm。
4、权利要求1的颗粒，其中所述的表面改良剂存在的量以重量计为0.1-90%。
5、权利要求1的颗粒，其中所述的抗癌剂选自：哌酰硫烷、哌酰硫胺（piposulfam）、喜树碱、鬼臼乙叉甙、紫杉酚、1，2，4-苯并三嗪-3-胺1，4-二氧化物、1，2，4-苯并三嗪-7-胺-1，4-二氧化物和视黄酸。
6、权利要求1的颗粒，其中所述的表面改良剂选自：聚乙烯醇、将环氧乙烷和环氧丙烷按顺序加到乙二胺和阿拉伯胶中所衍生的四官能嵌段共聚物、环氧乙烷和环氧丙烷的嵌段共聚物、聚氧乙烯脱水山梨糖醇脂肪酸酯和脂肪酸的脱水山梨糖醇酯。
7、权利要求1的颗粒，其中所述的抗癌剂是哌酰硫烷，所述的表面改良剂包括聚氧乙烯脱水山梨糖醇脂肪酸酯与脂肪酸的脱水山梨糖醇酯的结合物。
8、权利要求1的颗粒，其中所述的抗癌剂是喜树碱，所述的表面改良剂是聚乙烯醇。
9、权利要求1的颗粒，其中所述的抗癌剂是喜树碱，所述的表面改良剂是由向乙二胺中顺序添加环氧乙烷和环氧丙烷而衍生的四官能嵌段共聚物。
10、权利要求1的颗粒，其中所述的抗癌剂是喜树碱，所述表面改良剂是阿拉伯胶。
11、权利要求1的颗粒，其中所述的抗癌剂是鬼臼乙叉甙，所述表面改良剂是聚乙烯醇。
12、权利要求1的颗粒，其中所述的抗癌剂是鬼臼乙叉甙，所述表面改良剂是环氧乙烷和环氧丙烷的嵌段共聚物。
13、权利要求1的颗粒，其中所述的抗癌剂是鬼臼乙叉甙，所述表面改良剂是阿拉伯胶。
14、权利要求1的颗粒，其中所述的抗癌剂是紫杉酚，所述表面改良剂是聚乙烯醇。
15、权利要求1的颗粒，其中所述的抗癌剂是紫杉酚，所述表面改良剂是聚氧乙烯脱水山梨糖醇脂肪酸酯。
16、权利要求1的颗粒，其中所述的抗癌剂是紫杉酚，所述表面改良剂含聚氧然脱水山梨糖醇脂肪酸酯。
17、权利要求1的颗粒，其中所述的抗癌剂是1，2，4-苯并三嗪-3-胺1，4-二氧化物，所述表面改良剂是聚氧乙烯吡咯烷酮。
18、权利要求1的颗粒，其中所述的抗癌剂是1，2，4-苯并三嗪-7-胺1，4-二氧化物，所述表面改良剂是阿拉伯胶。
19、权利要求1的颗粒，其中所述的抗癌剂是1，2，4-苯并三嗪-7-胺1，4-二氧化物，所述表面改良剂是聚氧乙烯吡咯烷酮。
20、权利要求1的颗粒，其中所述的抗癌剂是1，2，4-苯并三嗪-7-胺1，4-二氧化物，所述表面改良剂是由向乙二胺中顺序添加环氧乙烷和环氧丙烷而衍生的四官能嵌段共聚物。
21、权利要求1的颗粒，其中所述的抗癌剂是视黄酸，所述的表面改良剂是四丁酚醛。
22、权利要求1的颗粒，其中所述的抗癌剂是哌酰硫胺，所述表面改良剂是聚乙烯醇。
23、权利要求1的颗粒，其中所述的抗癌剂是哌酰硫胺，所述表面改良剂是阿拉伯胶。
24、一种含权利要求1的颗粒的抗癌组合物。
25、一种治疗哺乳动物的方法，它包括给哺乳动物施用有效量的权利要求24中的抗癌组合物。
26、一种治疗哺乳动物的方法，它包括给哺乳动物施用有效量的抗癌剂，其改进在于：通过以权利要求1的颗粒的形式施用所述的抗癌剂，从而增加了所述抗癌剂的效力。
27、一种治疗哺乳动物的方法，它包括给哺乳动物施用有效量的抗癌剂，其改进在于：通过以权利要求1的颗粒的形式施用所述的抗癌剂，从而降低了所述抗癌剂的毒性。
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Families Citing this family (564)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6515009B1 (en) 1991-09-27 2003-02-04 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5811447A (en) 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6395494B1 (en) 1993-05-13 2002-05-28 Neorx Corporation Method to determine TGF-β
US6306421B1 (en) 1992-09-25 2001-10-23 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6251920B1 (en) 1993-05-13 2001-06-26 Neorx Corporation Prevention and treatment of cardiovascular pathologies
US6277410B1 (en) * 1992-10-08 2001-08-21 Supratek Pharma Inc. Copolymer compositions for oral delivery
FR2697752B1 (fr) * 1992-11-10 1995-04-14 Rhone Poulenc Rorer Sa Compositions antitumorales contenant des dérivés du taxane.
US5298262A (en) * 1992-12-04 1994-03-29 Sterling Winthrop Inc. Use of ionic cloud point modifiers to prevent particle aggregation during sterilization
US5346702A (en) * 1992-12-04 1994-09-13 Sterling Winthrop Inc. Use of non-ionic cloud point modifiers to minimize nanoparticle aggregation during sterilization
FR2698871B1 (fr) 1992-12-09 1995-02-24 Rhone Poulenc Rorer Sa Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent.
US6491938B2 (en) 1993-05-13 2002-12-10 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5981568A (en) 1993-01-28 1999-11-09 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6663881B2 (en) 1993-01-28 2003-12-16 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5525559A (en) * 1993-02-13 1996-06-11 Tioxide Specialties Limited Preparation of mixed powders
US6537579B1 (en) 1993-02-22 2003-03-25 American Bioscience, Inc. Compositions and methods for administration of pharmacologically active compounds
US6753006B1 (en) * 1993-02-22 2004-06-22 American Bioscience, Inc. Paclitaxel-containing formulations
US6096331A (en) 1993-02-22 2000-08-01 Vivorx Pharmaceuticals, Inc. Methods and compositions useful for administration of chemotherapeutic agents
US6749868B1 (en) 1993-02-22 2004-06-15 American Bioscience, Inc. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
US20070117862A1 (en) * 1993-02-22 2007-05-24 Desai Neil P Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
US20030133955A1 (en) * 1993-02-22 2003-07-17 American Bioscience, Inc. Methods and compositions useful for administration of chemotherapeutic agents
US20030068362A1 (en) * 1993-02-22 2003-04-10 American Bioscience, Inc. Methods and formulations for the delivery of pharmacologically active agents
US5439686A (en) * 1993-02-22 1995-08-08 Vivorx Pharmaceuticals, Inc. Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor
US5629327A (en) * 1993-03-01 1997-05-13 Childrens Hospital Medical Center Corp. Methods and compositions for inhibition of angiogenesis
US6228879B1 (en) 1997-10-16 2001-05-08 The Children's Medical Center Methods and compositions for inhibition of angiogenesis
US8143283B1 (en) * 1993-03-01 2012-03-27 The Children's Medical Center Corporation Methods for treating blood-born tumors with thalidomide
US6114355A (en) * 1993-03-01 2000-09-05 D'amato; Robert Methods and compositions for inhibition of angiogenesis
US5830436A (en) * 1993-03-30 1998-11-03 Duke University Method of mucociliary clearance in cystic fibrosis patients using alkylaryl polyether alcohol polymers
US5840277A (en) * 1993-03-30 1998-11-24 Charlotte Hospital Authority Treatment of chronic pulmonary inflammation
US5849263A (en) * 1993-03-30 1998-12-15 Charlotte-Mecklenburg Hospital Authority Pharmaceutical compositions containing alkylaryl polyether alcohol polymer
CH686761A5 (de) 1993-05-27 1996-06-28 Sandoz Ag Galenische Formulierungen.
US6441026B1 (en) 1993-11-08 2002-08-27 Aventis Pharma S.A. Antitumor compositions containing taxane derivatives
US5534270A (en) * 1995-02-09 1996-07-09 Nanosystems Llc Method of preparing stable drug nanoparticles
US5573783A (en) * 1995-02-13 1996-11-12 Nano Systems L.L.C. Redispersible nanoparticulate film matrices with protective overcoats
US5510118A (en) * 1995-02-14 1996-04-23 Nanosystems Llc Process for preparing therapeutic compositions containing nanoparticles
EP0810853B1 (en) * 1995-02-24 2004-08-25 Elan Pharma International Limited Aerosols containing nanoparticle dispersions
DE19512484A1 (de) * 1995-04-04 1996-10-17 Bayer Ag Kohlenhydratmodifizierte Cytostatika
US5731325A (en) * 1995-06-06 1998-03-24 Andrulis Pharmaceuticals Corp. Treatment of melanomas with thalidomide alone or in combination with other anti-melanoma agents
US7833543B2 (en) * 1995-06-07 2010-11-16 Durect Corporation High viscosity liquid controlled delivery system and medical or surgical device
US6413536B1 (en) 1995-06-07 2002-07-02 Southern Biosystems, Inc. High viscosity liquid controlled delivery system and medical or surgical device
WO1997004756A2 (en) * 1995-07-26 1997-02-13 Nanosystems L.L.C. Methacrylate backbone surfactants in nanoparticulate formulations
US6391338B1 (en) 1995-09-07 2002-05-21 Biovail Technologies Ltd. System for rendering substantially non-dissoluble bio-affecting agents bio-available
US5834025A (en) 1995-09-29 1998-11-10 Nanosystems L.L.C. Reduction of intravenously administered nanoparticulate-formulation-induced adverse physiological reactions
US6346510B1 (en) * 1995-10-23 2002-02-12 The Children's Medical Center Corporation Therapeutic antiangiogenic endostatin compositions
US5955509A (en) * 1996-05-01 1999-09-21 Board Of Regents, The University Of Texas System pH dependent polymer micelles
CN1219872A (zh) * 1996-05-24 1999-06-16 血管技术药物公司 治疗或预防身体通道疾病的组合物和方法
US20030195848A1 (en) * 1996-06-05 2003-10-16 David Felger Method of billing a purchase made over a computer network
AU3585397A (en) 1996-06-27 1998-01-14 G.D. Searle & Co. Particles comprising amphiphilic copolymers, having a cross-linked shell domain and an interior core domain, useful for pharmaceutical and other applications
US7255877B2 (en) * 1996-08-22 2007-08-14 Jagotec Ag Fenofibrate microparticles
US6465016B2 (en) 1996-08-22 2002-10-15 Research Triangle Pharmaceuticals Cyclosporiine particles
US8137684B2 (en) * 1996-10-01 2012-03-20 Abraxis Bioscience, Llc Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
PT1586322E (pt) * 1996-11-05 2008-10-27 Childrens Medical Center Composições que compreendem talidomida e dexametasona para o tratamento de cancro
US6515016B2 (en) 1996-12-02 2003-02-04 Angiotech Pharmaceuticals, Inc. Composition and methods of paclitaxel for treating psoriasis
FR2759293B1 (fr) * 1997-02-11 1999-04-30 Ethypharm Lab Prod Ethiques Microgranules contenant du cisplatine, procede de fabrication, preparation pharmaceutique et utilisation en polychimiotherapie ou en association avec une radiotherapie
WO1998035666A1 (en) * 1997-02-13 1998-08-20 Nanosystems Llc Formulations of nanoparticle naproxen tablets
US6045829A (en) 1997-02-13 2000-04-04 Elan Pharma International Limited Nanocrystalline formulations of human immunodeficiency virus (HIV) protease inhibitors using cellulosic surface stabilizers
DK1014990T3 (da) * 1997-03-07 2006-12-11 Sanofi Aventis Us Llc Antitumorkombination af 3 amino-1,2,4 benzotriazin-1,4 dioxid/paclitaxel/platin
US20050004049A1 (en) * 1997-03-11 2005-01-06 Elan Pharma International Limited Novel griseofulvin compositions
AU6853498A (en) * 1997-04-22 1998-11-13 Nippon Kayaku Kabushiki Kaisha Flutamide preparations and method for manufacturing the same
US20020039594A1 (en) * 1997-05-13 2002-04-04 Evan C. Unger Solid porous matrices and methods of making and using the same
US6051558A (en) * 1997-05-28 2000-04-18 Southern Biosystems, Inc. Compositions suitable for controlled release of the hormone GnRH and its analogs
US20060025328A1 (en) * 1997-05-28 2006-02-02 Burns Patrick J Compositions suitable for controlled release of the hormone GnRH and its analogs
EP1023050B1 (en) * 1997-06-27 2013-09-25 Abraxis BioScience, LLC Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
US20030199425A1 (en) * 1997-06-27 2003-10-23 Desai Neil P. Compositions and methods for treatment of hyperplasia
US8853260B2 (en) * 1997-06-27 2014-10-07 Abraxis Bioscience, Llc Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
UA72189C2 (uk) 1997-11-17 2005-02-15 Янссен Фармацевтика Н.В. Фармацевтична композиція, що містить водну суспензію субмікронних ефірів 9-гідроксирисперидон жирних кислот
US20020147143A1 (en) 1998-03-18 2002-10-10 Corixa Corporation Compositions and methods for the therapy and diagnosis of lung cancer
US6673828B1 (en) * 1998-05-11 2004-01-06 Children's Medical Center Corporation Analogs of 2-Phthalimidinoglutaric acid
CN1245955C (zh) 1998-05-29 2006-03-22 斯凯伊药品加拿大公司 热保护微粒组合物及其最终蒸汽灭菌的方法
US6153225A (en) * 1998-08-13 2000-11-28 Elan Pharma International Limited Injectable formulations of nanoparticulate naproxen
AU759641B2 (en) * 1998-08-19 2003-04-17 Skyepharma Canada Inc. Injectable aqueous dispersions of propofol
US6350786B1 (en) 1998-09-22 2002-02-26 Hoffmann-La Roche Inc. Stable complexes of poorly soluble compounds in ionic polymers
US20030235557A1 (en) 1998-09-30 2003-12-25 Corixa Corporation Compositions and methods for WT1 specific immunotherapy
US20040013613A1 (en) * 2001-05-18 2004-01-22 Jain Rajeev A Rapidly disintegrating solid oral dosage form
US20080213378A1 (en) * 1998-10-01 2008-09-04 Elan Pharma International, Ltd. Nanoparticulate statin formulations and novel statin combinations
US8293277B2 (en) * 1998-10-01 2012-10-23 Alkermes Pharma Ireland Limited Controlled-release nanoparticulate compositions
EP2266542A3 (en) * 1998-10-01 2013-07-31 Elan Pharma International Limited Controlled release nanoparticulate compositions
US8236352B2 (en) * 1998-10-01 2012-08-07 Alkermes Pharma Ireland Limited Glipizide compositions
US20070160675A1 (en) * 1998-11-02 2007-07-12 Elan Corporation, Plc Nanoparticulate and controlled release compositions comprising a cephalosporin
US20090297602A1 (en) * 1998-11-02 2009-12-03 Devane John G Modified Release Loxoprofen Compositions
NZ511442A (en) * 1998-11-02 2003-02-28 Elan Corp Plc Multiparticulate modified release composition for multiple dosing of ADD patients with methylphenidate HCl
US6969529B2 (en) 2000-09-21 2005-11-29 Elan Pharma International Ltd. Nanoparticulate compositions comprising copolymers of vinyl pyrrolidone and vinyl acetate as surface stabilizers
US6375986B1 (en) 2000-09-21 2002-04-23 Elan Pharma International Ltd. Solid dose nanoparticulate compositions comprising a synergistic combination of a polymeric surface stabilizer and dioctyl sodium sulfosuccinate
US7521068B2 (en) * 1998-11-12 2009-04-21 Elan Pharma International Ltd. Dry powder aerosols of nanoparticulate drugs
US6428814B1 (en) 1999-10-08 2002-08-06 Elan Pharma International Ltd. Bioadhesive nanoparticulate compositions having cationic surface stabilizers
US20040141925A1 (en) * 1998-11-12 2004-07-22 Elan Pharma International Ltd. Novel triamcinolone compositions
US6984404B1 (en) 1998-11-18 2006-01-10 University Of Florida Research Foundation, Inc. Methods for preparing coated drug particles and pharmaceutical formulations thereof
KR20010073232A (ko) 1998-11-20 2001-07-31 추후제출 분산성 인지질로 안정화된 마이크로입자
US20040009535A1 (en) 1998-11-27 2004-01-15 Celltech R&D, Inc. Compositions and methods for increasing bone mineralization
WO2000032773A1 (en) 1998-11-27 2000-06-08 Darwin Discovery Ltd. Compositions and methods for increasing bone mineralization
DE19856432A1 (de) 1998-12-08 2000-06-15 Basf Ag Nanopartikuläre Kern-Schale Systeme sowie deren Verwendung in pharmazeutischen und kosmetischen Zubereitungen
US6040330A (en) * 1999-01-08 2000-03-21 Bionumerik Pharmaceuticals, Inc. Pharmaceutical formulations of taxanes
US6267989B1 (en) 1999-03-08 2001-07-31 Klan Pharma International Ltd. Methods for preventing crystal growth and particle aggregation in nanoparticulate compositions
EP1754488A1 (en) 1999-05-24 2007-02-21 Introgen Therapeutics, Inc. Methods and compositions for non-viral gene therapy for treatment of hyperproliferative diseases
US6444223B1 (en) 1999-05-28 2002-09-03 Alkermes Controlled Therapeutics, Inc. Method of producing submicron particles of a labile agent and use thereof
US6406745B1 (en) * 1999-06-07 2002-06-18 Nanosphere, Inc. Methods for coating particles and particles produced thereby
US20090104273A1 (en) * 1999-06-22 2009-04-23 Elan Pharma International Ltd. Novel nifedipine compositions
US20040115134A1 (en) * 1999-06-22 2004-06-17 Elan Pharma International Ltd. Novel nifedipine compositions
US6656504B1 (en) * 1999-09-09 2003-12-02 Elan Pharma International Ltd. Nanoparticulate compositions comprising amorphous cyclosporine and methods of making and using such compositions
ES2241663T3 (es) * 1999-09-21 2005-11-01 Skyepharma Canada Inc. Composiciones particuladas modificadas superficialmente de substancias biologicamente activas.
EP2289549A3 (en) 1999-10-01 2011-06-15 Immunogen, Inc. Immunoconjugates for treating cancer
US20040009229A1 (en) * 2000-01-05 2004-01-15 Unger Evan Charles Stabilized nanoparticle formulations of camptotheca derivatives
EP1166225A1 (en) 2000-01-31 2002-01-02 Collaborative Technologies, Inc. Method and system for producing customized cosmetic and pharmaceutical formulations on demand
GB0002952D0 (en) * 2000-02-09 2000-03-29 Pharma Mar Sa Process for producing kahalalide F compounds
ATE487733T1 (de) 2000-02-23 2010-11-15 Glaxosmithkline Biolog Sa Neue verbindungen
US20040002068A1 (en) 2000-03-01 2004-01-01 Corixa Corporation Compositions and methods for the detection, diagnosis and therapy of hematological malignancies
US20040156872A1 (en) * 2000-05-18 2004-08-12 Elan Pharma International Ltd. Novel nimesulide compositions
US6316029B1 (en) 2000-05-18 2001-11-13 Flak Pharma International, Ltd. Rapidly disintegrating solid oral dosage form
US10293056B1 (en) 2000-05-24 2019-05-21 Board Of Regents, The University Of Texas System Methods and compositions for non-viral gene therapy for treatment of hyperproliferative diseases
ES2374620T3 (es) 2000-06-20 2012-02-20 Corixa Corporation Antígeno mtb32a de mycobacterium tuberculosis con el sitio activo inactivado y proteínas de fusión de los mismos.
EP1961819A3 (en) 2000-06-28 2008-11-12 Corixa Corporation Composition and methods for the therapy and diagnosis of lung cancer
US7276249B2 (en) * 2002-05-24 2007-10-02 Elan Pharma International, Ltd. Nanoparticulate fibrate formulations
US20030224058A1 (en) * 2002-05-24 2003-12-04 Elan Pharma International, Ltd. Nanoparticulate fibrate formulations
US7198795B2 (en) * 2000-09-21 2007-04-03 Elan Pharma International Ltd. In vitro methods for evaluating the in vivo effectiveness of dosage forms of microparticulate of nanoparticulate active agent compositions
US20080241070A1 (en) * 2000-09-21 2008-10-02 Elan Pharma International Ltd. Fenofibrate dosage forms
US7998507B2 (en) * 2000-09-21 2011-08-16 Elan Pharma International Ltd. Nanoparticulate compositions of mitogen-activated protein (MAP) kinase inhibitors
CN1469735A (zh) * 2000-10-16 2004-01-21 ����˹��ҩ�﹫˾ 米托蒽醌的脂质体制剂
WO2002064083A2 (en) * 2000-11-30 2002-08-22 The Children's Medical Center Corporation Synthesis of 3-amino-thalidomide and its enantiomers
EP1404359A2 (en) * 2000-12-07 2004-04-07 Board Of Regents, The University Of Texas System Methods of treatment involving human mda-7
US20040256749A1 (en) * 2000-12-22 2004-12-23 Mahesh Chaubal Process for production of essentially solvent-free small particles
US7193084B2 (en) * 2000-12-22 2007-03-20 Baxter International Inc. Polymorphic form of itraconazole
US7037528B2 (en) * 2000-12-22 2006-05-02 Baxter International Inc. Microprecipitation method for preparing submicron suspensions
US20040022862A1 (en) * 2000-12-22 2004-02-05 Kipp James E. Method for preparing small particles
US8067032B2 (en) * 2000-12-22 2011-11-29 Baxter International Inc. Method for preparing submicron particles of antineoplastic agents
US20050048126A1 (en) * 2000-12-22 2005-03-03 Barrett Rabinow Formulation to render an antimicrobial drug potent against organisms normally considered to be resistant to the drug
US6977085B2 (en) * 2000-12-22 2005-12-20 Baxter International Inc. Method for preparing submicron suspensions with polymorph control
US20030096013A1 (en) * 2000-12-22 2003-05-22 Jane Werling Preparation of submicron sized particles with polymorph control
US6951656B2 (en) * 2000-12-22 2005-10-04 Baxter International Inc. Microprecipitation method for preparing submicron suspensions
US6884436B2 (en) * 2000-12-22 2005-04-26 Baxter International Inc. Method for preparing submicron particle suspensions
US6623761B2 (en) 2000-12-22 2003-09-23 Hassan Emadeldin M. Method of making nanoparticles of substantially water insoluble materials
US20030072807A1 (en) * 2000-12-22 2003-04-17 Wong Joseph Chung-Tak Solid particulate antifungal compositions for pharmaceutical use
US9700866B2 (en) * 2000-12-22 2017-07-11 Baxter International Inc. Surfactant systems for delivery of organic compounds
DK1413331T3 (da) * 2001-01-26 2007-12-10 Schering Corp Kombinationer af peroxisomproliferatoraktiveret receptor (PPAR)-aktivatoren fenofibrat og sterolabsorptionsinhibitoren ezetimib til vaskulære indikationer
US20060287254A1 (en) * 2001-01-26 2006-12-21 Schering Corporation Use of substituted azetidinone compounds for the treatment of sitosterolemia
US6497896B2 (en) 2001-02-12 2002-12-24 Supergen, Inc. Method for administering camptothecins via injection of a pharmaceutical composition comprising microdroplets containing a camptothecin
US20020150615A1 (en) * 2001-02-12 2002-10-17 Howard Sands Injectable pharmaceutical composition comprising microdroplets of a camptothecin
US6509027B2 (en) 2001-02-12 2003-01-21 Supergen, Inc. Injectable pharmaceutical composition comprising coated particles of camptothecin
EP1372394A1 (en) 2001-04-03 2004-01-02 Schering Corporation Antifungal composition with enhanced bioavailability
CA2446788A1 (en) 2001-05-09 2002-11-14 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US6976647B2 (en) * 2001-06-05 2005-12-20 Elan Pharma International, Limited System and method for milling materials
WO2003000228A2 (en) * 2001-06-22 2003-01-03 Elan Pharma International Ltd. Method for high through put screening using a small scale mill or microfluidics
US20030054042A1 (en) * 2001-09-14 2003-03-20 Elaine Liversidge Stabilization of chemical compounds using nanoparticulate formulations
PT1429731E (pt) * 2001-09-19 2007-04-30 Elan Pharma Int Ltd Formulações de insulina nanoparticulada
US7053080B2 (en) * 2001-09-21 2006-05-30 Schering Corporation Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors
DK1429756T3 (da) * 2001-09-21 2007-03-19 Schering Corp Behandling af xanthoma med azetidinonderivater som sterolabsorptionsinhibitorer
US20060003012A9 (en) * 2001-09-26 2006-01-05 Sean Brynjelsen Preparation of submicron solid particle suspensions by sonication of multiphase systems
EP1429749A2 (en) * 2001-09-26 2004-06-23 Baxter International Inc. Preparation of submicron sized nanoparticles via dispersion and solvent or liquid phase removal
DE60222160T2 (de) * 2001-10-12 2008-06-12 Elan Pharma International Ltd., Athlone Zusammensetzungen mit einer kombination aus eigenschaften sofortiger freisetzung und kontrollierter freisetzung
US20030087837A1 (en) * 2001-10-15 2003-05-08 Jonas Jeffrey M. Compositions and methods for delivery of poorly water soluble drugs and methods of treatment
US7112340B2 (en) * 2001-10-19 2006-09-26 Baxter International Inc. Compositions of and method for preparing stable particles in a frozen aqueous matrix
WO2003039601A1 (en) * 2001-11-07 2003-05-15 Imcor Pharmaceutical Company Methods for vascular imaging using nanoparticulate contrast agents
BR0117191A (pt) * 2001-12-06 2005-05-10 Ranbaxy Lab Ltd Composições nanoparticuladas de isotretinoina
UA76810C2 (uk) * 2001-12-10 2006-09-15 Мерк Енд Ко., Інк. Фармацевтична композиція антагоніста рецептора тахікініну у формі наночастинок
WO2003053220A2 (en) 2001-12-17 2003-07-03 Corixa Corporation Compositions and methods for the therapy and diagnosis of inflammatory bowel disease
IL162183A0 (en) * 2001-12-21 2005-11-20 Celator Technologies Inc Polymer-lipid delivery vehicles and methods for the preparation thereof
US20030129242A1 (en) * 2002-01-04 2003-07-10 Bosch H. William Sterile filtered nanoparticulate formulations of budesonide and beclomethasone having tyloxapol as a surface stabilizer
AU2003210517A1 (en) * 2002-02-04 2003-09-02 Elan Pharma International, Ltd. Drug nanoparticles with lysozyme surface stabiliser
US20040101566A1 (en) * 2002-02-04 2004-05-27 Elan Pharma International Limited Novel benzoyl peroxide compositions
US20030164219A1 (en) * 2002-02-20 2003-09-04 Joerg Brahm Headliner/duct assembly and welding process therefor
WO2003075952A1 (en) * 2002-03-05 2003-09-18 Board Of Regents, The University Of Texas System Methods of enhancing immune induction involving mda-7
AU2003222027A1 (en) * 2002-03-20 2003-10-08 Elan Pharma International Limited Fast dissolving dosage forms having reduced friability
US20080220075A1 (en) * 2002-03-20 2008-09-11 Elan Pharma International Ltd. Nanoparticulate compositions of angiogenesis inhibitors
EP1490030B2 (en) * 2002-03-20 2010-07-14 Elan Pharma International Limited Nanoparticulate compositions of angiogenesis inhibitors
EP1800666A1 (en) * 2002-03-20 2007-06-27 Elan Pharma International Limited Nanoparticulate compositions of angiogenesis inhibitors
US20040076586A1 (en) * 2002-03-28 2004-04-22 Reinhard Koening Compositions and methods for delivering pharmaceutically active agents using nanoparticulates
WO2003087763A2 (en) 2002-04-03 2003-10-23 Celltech R & D, Inc. Association of polymorphisms in the sost gene region with bone mineral density
US7332469B2 (en) 2002-04-05 2008-02-19 Board Of Regents The University Of Texas System Intrapleural single-chain urokinase alone or complexed to its soluble receptor protects against pleural adhesions
ES2380318T3 (es) 2002-04-12 2012-05-10 Alkermes Pharma Ireland Limited Formulaciones nanoparticulares de megestrol
US9101540B2 (en) * 2002-04-12 2015-08-11 Alkermes Pharma Ireland Limited Nanoparticulate megestrol formulations
US20100226989A1 (en) * 2002-04-12 2010-09-09 Elan Pharma International, Limited Nanoparticulate megestrol formulations
US20040105889A1 (en) * 2002-12-03 2004-06-03 Elan Pharma International Limited Low viscosity liquid dosage forms
US7101576B2 (en) * 2002-04-12 2006-09-05 Elan Pharma International Limited Nanoparticulate megestrol formulations
EP1503737B1 (en) * 2002-05-06 2009-01-07 Elan Pharma International Limited Nanoparticulate nystatin formulations
DE60328486D1 (de) * 2002-05-24 2009-09-03 Angiotech Int Ag Zusammensetzungen und verfahren zur beschichtung medizinischer implantate
US8313760B2 (en) * 2002-05-24 2012-11-20 Angiotech International Ag Compositions and methods for coating medical implants
US20070264348A1 (en) * 2002-05-24 2007-11-15 Elan Pharma International, Ltd. Nanoparticulate fibrate formulations
KR100530369B1 (ko) * 2002-05-27 2005-11-22 이영환 항암물질에 나노입자를 결합시킨 주사 제형의 약물 시스템
WO2003103632A1 (en) * 2002-06-10 2003-12-18 Elan Pharma International, Ltd. Nanoparticulate polycosanol formulations and novel polycosanol combinations
EP1531799A1 (en) * 2002-06-10 2005-05-25 Elan Pharma International Limited Nanoparticulate formulations comprising hmg coa reductase inhibitor derivatives ("statins"), novel combinations thereof as well as manufacturing of these pharmaceutical compositions
US20040001889A1 (en) 2002-06-25 2004-01-01 Guohua Chen Short duration depot formulations
JP4776229B2 (ja) * 2002-07-16 2011-09-21 エラン ファーマ インターナショナル，リミティド 安定なナノ粒子活性物質の液体投与組成物
CA2818693C (en) 2002-08-12 2016-05-17 Jennerex, Inc. Methods and compositions concerning poxviruses and cancer
RU2005103625A (ru) 2002-08-12 2005-08-20 Пфайзер Продактс Инк. (Us) Фармацевтические композиции полуупорядоченных лекарств и полимеров
DK1553927T3 (da) * 2002-09-11 2011-01-31 Elan Pharma Int Ltd Gel-stabiliserede, nanopartikulære aktivstof-sammensætninger
CA2500908A1 (en) * 2002-10-04 2004-04-22 Elan Pharma International Limited Gamma irradiation of solid nanoparticulate active agents
US6966990B2 (en) 2002-10-11 2005-11-22 Ferro Corporation Composite particles and method for preparing
GB0304367D0 (en) * 2003-02-26 2003-04-02 Pharma Mar Sau Methods for treating psoriasis
ES2365012T3 (es) * 2002-11-12 2011-09-20 Elan Pharma International Limited Formas farmacéuticas sólidas de desintegración rápida que no son friables y que comprenden pululano.
EP1935407A1 (en) * 2002-12-03 2008-06-25 Elan Pharma International Limited Low viscosity liquid dosage forms
SI1585548T1 (sl) 2002-12-09 2018-11-30 Abraxis Bioscience, Llc Sestave in metode odmerjanja farmakoloških sredstev
EP2218448B1 (en) * 2002-12-13 2015-09-23 Durect Corporation Oral drug delivery system comprising high viscosity liquid carrier materials
WO2004058216A2 (en) * 2002-12-17 2004-07-15 Elan Pharma International Ltd. Milling microgram quantities of nanoparticulate candidate compounds
ES2639812T3 (es) 2003-01-06 2017-10-30 Corixa Corporation Ciertos compuestos de fosfato de aminoalquil glucosaminida y sus usos
US7960522B2 (en) 2003-01-06 2011-06-14 Corixa Corporation Certain aminoalkyl glucosaminide phosphate compounds and their use
JP4469846B2 (ja) * 2003-01-31 2010-06-02 エラン ファーマ インターナショナル，リミティド ナノ粒子状トピラメート製剤
US20040208833A1 (en) * 2003-02-04 2004-10-21 Elan Pharma International Ltd. Novel fluticasone formulations
US6931888B2 (en) * 2003-02-07 2005-08-23 Ferro Corporation Lyophilization method and apparatus for producing particles
US7083748B2 (en) * 2003-02-07 2006-08-01 Ferro Corporation Method and apparatus for continuous particle production using supercritical fluid
US8512727B2 (en) 2003-03-03 2013-08-20 Alkermes Pharma Ireland Limited Nanoparticulate meloxicam formulations
KR20060002793A (ko) * 2003-03-03 2006-01-09 더 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 Ｍｄａ-7을 포함하는 방법 및 조성물
US20100297252A1 (en) 2003-03-03 2010-11-25 Elan Pharma International Ltd. Nanoparticulate meloxicam formulations
US7459442B2 (en) * 2003-03-07 2008-12-02 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
MXPA05009501A (es) * 2003-03-07 2005-10-18 Schering Corp Compuestos de azetidinona sustituidos, formulaciones y usos de los mismos para el tratamiento de hipercolesterolemia.
US7235543B2 (en) * 2003-03-07 2007-06-26 Schering Corporation Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
CN102697737B (zh) * 2003-04-03 2014-03-19 杰西.L.-S.奥 负载肿瘤靶向药物的颗粒
US20060008531A1 (en) * 2003-05-08 2006-01-12 Ferro Corporation Method for producing solid-lipid composite drug particles
DE10323597A1 (de) * 2003-05-19 2004-12-09 Aesculap Ag & Co. Kg Medizintechnisches Produkt, Verfahren zu seiner Herstellung und Verwendung
BRPI0410646A (pt) * 2003-05-20 2006-07-04 Ranbaxy Lab Ltd composições farmacêuticas de acitretina e processo para sua preparação
EP1626742A1 (en) * 2003-05-22 2006-02-22 Elan Pharma International Limited Sterilization of dispersions of nanoparticulate active agents with gamma radiation
JP4688802B2 (ja) 2003-06-16 2011-05-25 セルテック アール アンド ディー， インコーポレイテッド 骨の鉱化作用を増大させるためのスクレロスチンに特異的な抗体および方法
US20050106310A1 (en) * 2003-07-02 2005-05-19 Green John H. Designed particle agglomeration
ES2559828T3 (es) 2003-07-16 2016-02-16 Protiva Biotherapeutics Inc. ARN de interferencia encapsulado en lípidos
ATE415946T1 (de) * 2003-08-08 2008-12-15 Elan Pharma Int Ltd Neue metaxalon-zusammensetzungen
US7419996B2 (en) * 2003-08-13 2008-09-02 The University Of Houston Parenteral and oral formulations of benzimidazoles
GB0327723D0 (en) * 2003-09-15 2003-12-31 Vectura Ltd Pharmaceutical compositions
AU2004285468B2 (en) 2003-10-22 2011-02-24 Fred Hutchinson Cancer Research Center Methods, compositions and devices for inducing stasis in cells, tissues, organs, and organisms
ES2366646T3 (es) * 2003-11-05 2011-10-24 Elan Pharma International Limited Composiciones en forma de nanopartículas que tienen un péptido como estabilizante superficial.
AU2004293463A1 (en) * 2003-11-20 2005-06-09 Angiotech International Ag Implantable sensors and implantable pumps and anti-scarring agents
WO2005051511A1 (ja) * 2003-11-28 2005-06-09 Mitsubishi Chemical Corporation 有機化合物微粒子の製造方法
CA2548220A1 (en) * 2003-12-01 2005-09-09 Introgen Therapeutics, Inc. Use of mda-7 to inhibit infection by pathogenic organisms
US20070281041A1 (en) * 2004-03-02 2007-12-06 Introgen Therapeutics, Inc. Compositions and Methods Involving MDA-7 for the Treatment of Cancer
WO2005095950A1 (en) * 2004-03-30 2005-10-13 Pfizer Products Inc. Method and device for evaluation of pharmaceutical compositions
US20050220866A1 (en) * 2004-04-02 2005-10-06 Dr. Reddy's Laboratories Limited Novel capsule formulations of etoposide for oral use
AU2005285513B2 (en) 2004-05-25 2011-02-24 Oregon Health And Science University SIV and HIV vaccination using RhCMV- and HCMV-based vaccine vectors
US7871632B2 (en) * 2004-07-12 2011-01-18 Adventrx Pharmaceuticals, Inc. Compositions for delivering highly water soluble drugs
KR20070043894A (ko) * 2004-08-19 2007-04-25 알자 코포레이션 제어 방출형 나노입자 활성제 제제 제형 및 방법
EP1797934A4 (en) * 2004-09-07 2009-09-02 Mitsubishi Chem Corp METHOD FOR MANUFACTURING FINULY PARTICULATE SUBSTANCE AND FINALLY PARTICULATE SUBSTANCE
EP1809329B1 (en) * 2004-09-17 2011-12-21 Durect Corporation Sustained local anesthetic composition containing saib
WO2006036278A2 (en) 2004-09-18 2006-04-06 University Of Maryland, Baltimore THERAPEUTIC AGENTS TARGETING THE NCCa-ATP CHANNEL AND METHODS OF USE THEREOF
AU2005287090A1 (en) 2004-09-18 2006-03-30 Department Of Veterans Affairs Therapeutic agents targeting the NCca-ATP channel and methods of use thereof
JP5324098B2 (ja) * 2004-11-16 2013-10-23 アルケルメス ファーマ アイルランド リミテッド 注射可能なナノ粒子のオランザピン製剤
US20090155331A1 (en) * 2005-11-16 2009-06-18 Elan Pharma International Limited Injectable nanoparticulate olanzapine formulations
UA89513C2 (uk) * 2004-12-03 2010-02-10 Элан Фарма Интернешнл Лтд. Стабільна композиція з наночастинок ралоксифену гідрохлориду
MX2007007342A (es) * 2004-12-15 2007-12-11 Elan Pharma Int Ltd Formulaciones de tacrolimus nanoparticuladas.
WO2006069098A1 (en) * 2004-12-22 2006-06-29 Elan Pharma International Ltd. Nanoparticulate bicalutamide formulations
MX2007008212A (es) * 2005-01-06 2007-08-16 Elan Pharma Int Ltd Formulaciones de candesartan en nanoparticulas.
CA2597329C (en) * 2005-02-08 2016-10-11 Board Of Regents, The University Of Texas System Compositions and methods involving mda-7 for the treatment of cancer
EP1853234A2 (en) * 2005-02-15 2007-11-14 Elan Pharma International Limited Aerosol and injectable formulations of nanoparticulate benzodiazepine
PL1853250T3 (pl) 2005-02-18 2012-03-30 Abraxis Bioscience Llc Kombinacje i sposoby podawania środków terapeutycznych oraz terapia skojarzona
US8735394B2 (en) 2005-02-18 2014-05-27 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
CA2598441A1 (en) * 2005-02-24 2006-08-31 Elan Pharma International Limited Nanoparticulate formulations of docetaxel and analogues thereof
AU2005100176A4 (en) * 2005-03-01 2005-04-07 Gym Tv Pty Ltd Garbage bin clip
WO2006096462A1 (en) * 2005-03-03 2006-09-14 Elan Pharma International Limited Nanoparticulate compositions of heterocyclic amide derivatives
WO2006099121A2 (en) * 2005-03-10 2006-09-21 Elan Pharma International Limited Formulations of a nanoparticulate finasteride, dutasteride and tamsulosin hydrochloride, and mixtures thereof
BRPI0606283A2 (pt) * 2005-03-16 2009-06-09 Elan Pharma Int Ltd formulações de antagonista de receptor de leucotrieno/corticosteróide em nanopartìcula
CN101198316A (zh) * 2005-03-17 2008-06-11 伊兰制药国际有限公司 纳米微粒双膦酸盐组合物
WO2006101972A2 (en) * 2005-03-17 2006-09-28 Elan Pharma International Limited Injectable compositions of nanoparticulate immunosuppressive compounds
MX2007011772A (es) * 2005-03-23 2007-12-05 Elan Pharma Int Ltd Formulaciones de antihistaminico y corticosteroide de materia en nanoparticulas.
EP2392347A3 (en) 2005-03-31 2012-01-18 GlaxoSmithKline Biologicals S.A. Vaccines against chlamydial infection
JP2008535921A (ja) * 2005-04-12 2008-09-04 エラン・ファルマ・インターナショナル・リミテッド シクロスポリンを含むナノ粒子および放出調節された組成物
US20060246141A1 (en) * 2005-04-12 2006-11-02 Elan Pharma International, Limited Nanoparticulate lipase inhibitor formulations
BRPI0607537A2 (pt) * 2005-04-12 2009-09-15 Elan Pharma Int Ltd formulações de derivado de quinazolina nanoparticulado
ITMI20050739A1 (it) * 2005-04-22 2006-10-23 Effebi Spa Piastrina di connsessione valvola-attuatore
JP5749881B2 (ja) 2005-04-22 2015-07-15 ユニヴェルシテ デ ジュネーブ ポリラクチド組成物およびその使用
KR101352806B1 (ko) 2005-04-29 2014-02-17 인펙셔스 디지즈 리서치 인스티튜트 (아이디알아이) 결핵균 감염을 예방 또는 치료하기 위한 신규한 방법
US7592429B2 (en) 2005-05-03 2009-09-22 Ucb Sa Sclerostin-binding antibody
US8003108B2 (en) 2005-05-03 2011-08-23 Amgen Inc. Sclerostin epitopes
WO2006132752A1 (en) * 2005-05-10 2006-12-14 Elan Pharma International Limited Nanoparticulate and controlled release compositions comprising vitamin k2
JP2008540550A (ja) * 2005-05-10 2008-11-20 エラン・ファルマ・インターナショナル・リミテッド ビタミンｋ２を含むナノ粒子および制御放出組成物
US20100028439A1 (en) * 2005-05-23 2010-02-04 Elan Pharma International Limited Nanoparticulate stabilized anti-hypertensive compositions
AU2006309295B2 (en) * 2005-06-03 2012-04-26 Elan Pharma International Limited Nanoparticulate acetaminophen formulations
CA2610448A1 (en) * 2005-06-03 2006-12-14 Elan Pharma International, Limited Nanoparticulate imatinib mesylate formulations
WO2006133045A1 (en) * 2005-06-03 2006-12-14 Elan Pharma International, Limited Nanoparticulate benidipine compositions
WO2008073068A1 (en) 2005-06-08 2008-06-19 Elan Pharma International Limited Nanoparticulate and controlled release compositions comprising cefditoren
EP1898882B1 (en) * 2005-06-09 2009-10-28 Elan Pharma International Limited Nanoparticulate ebastine formulations
AU2006259606A1 (en) * 2005-06-13 2006-12-28 Elan Pharma International, Limited Nanoparticulate clopidogrel and aspirin combination formulations
US20060280787A1 (en) * 2005-06-14 2006-12-14 Baxter International Inc. Pharmaceutical formulation of the tubulin inhibitor indibulin for oral administration with improved pharmacokinetic properties, and process for the manufacture thereof
MX2007015183A (es) * 2005-06-14 2008-02-19 Baxter Int Formulaciones farmaceuticas para minimizar las interacciones farmaco-farmaco.
US20100221327A1 (en) * 2005-06-15 2010-09-02 Elan Pharma International Limited Nanoparticulate azelnidipine formulations
CA2613466A1 (en) * 2005-06-22 2007-01-04 Elan Pharma International, Limited Nanoparticulate megestrol formulations
US20070015719A1 (en) * 2005-07-07 2007-01-18 Elan Pharma International Limited Nanoparticulate clarithromycin formulations
US20070027105A1 (en) 2005-07-26 2007-02-01 Alza Corporation Peroxide removal from drug delivery vehicle
WO2007016597A2 (en) * 2005-07-29 2007-02-08 The Regents Of The University Of California Targeting tnf-alpha converting enzyme (tace)-dependent growth factor shedding in cancer therapy
GB0516549D0 (en) * 2005-08-12 2005-09-21 Sulaiman Brian Milling system
US8980246B2 (en) 2005-09-07 2015-03-17 Sillajen Biotherapeutics, Inc. Oncolytic vaccinia virus cancer therapy
WO2007030668A2 (en) * 2005-09-07 2007-03-15 Jennerex Biotherapeutics Ulc Systemic treatment of metastatic and/or systemically-disseminated cancers using gm-csf-expressing poxviruses
JP2009507925A (ja) * 2005-09-13 2009-02-26 エラン ファーマ インターナショナル リミテッド ナノ粒子タダラフィル製剤
US20070148100A1 (en) * 2005-09-15 2007-06-28 Elan Pharma International, Limited Nanoparticulate aripiprazole formulations
WO2007041079A2 (en) * 2005-09-30 2007-04-12 Alza Corporation Banded controlled release nanoparticle active agent formulation dosage forms and methods
KR20080080119A (ko) * 2005-11-15 2008-09-02 백스터 인터내셔널 인코포레이티드 리폭시게나제 억제제의 조성물
CN101360422B (zh) 2005-11-23 2013-10-23 得克萨斯大学体系董事会 致癌Ras特异性细胞毒化合物及其使用方法
ES2812250T3 (es) * 2005-11-28 2021-03-16 Marinus Pharmaceuticals Inc Formulaciones de ganaxolona y procedimientos para la preparación y uso de las mismas
US20090062341A1 (en) 2005-11-28 2009-03-05 Dalton James T Nuclear receptor binding agents
WO2007120368A2 (en) 2006-01-09 2007-10-25 The Regents Of The University Of California Immunostimulatory combinations for vaccine adjuvants
WO2007092944A2 (en) * 2006-02-08 2007-08-16 Introgen Therapeutics, Inc. Compositions and methods involving gene therapy and proteasome modulation
US8367112B2 (en) * 2006-02-28 2013-02-05 Alkermes Pharma Ireland Limited Nanoparticulate carverdilol formulations
US20080166411A1 (en) * 2006-04-10 2008-07-10 Pfizer Inc Injectable Depot Formulations And Methods For Providing Sustained Release Of Poorly Soluble Drugs Comprising Nanoparticles
WO2007123468A1 (en) * 2006-04-24 2007-11-01 Bruce Medical Ab Polymer-based anti-cancer agents
JP4204634B2 (ja) * 2006-05-15 2009-01-07 株式会社荏原製作所 難水溶性医薬
NZ573555A (en) * 2006-05-30 2012-09-28 Elan Pharma Int Ltd Nanoparticulate posaconazole formulations
JP2009543797A (ja) * 2006-07-10 2009-12-10 エラン ファーマ インターナショナル，リミティド ナノ粒子ソラフェニブ製剤
CL2007002567A1 (es) 2006-09-08 2008-02-01 Amgen Inc Proteinas aisladas de enlace a activina a humana.
US8652782B2 (en) 2006-09-12 2014-02-18 Longhorn Vaccines & Diagnostics, Llc Compositions and methods for detecting, identifying and quantitating mycobacterial-specific nucleic acids
US9481912B2 (en) 2006-09-12 2016-11-01 Longhorn Vaccines And Diagnostics, Llc Compositions and methods for detecting and identifying nucleic acid sequences in biological samples
US8097419B2 (en) 2006-09-12 2012-01-17 Longhorn Vaccines & Diagnostics Llc Compositions and method for rapid, real-time detection of influenza A virus (H1N1) swine 2009
US8080645B2 (en) * 2007-10-01 2011-12-20 Longhorn Vaccines & Diagnostics Llc Biological specimen collection/transport compositions and methods
US8481023B2 (en) 2006-09-15 2013-07-09 Ottawa Hospital Research Institute Oncolytic rhabdovirus
CA2663962A1 (en) 2006-09-19 2008-03-27 Asuragen, Inc. Mir-15, mir-26, mir-31,mir-145, mir-147, mir-188, mir-215, mir-216, mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention
MX2009003092A (es) * 2006-09-22 2009-05-08 Labopharm Inc Composiciones y metodos para suministro de farmaco dirigido a ph.
US8466154B2 (en) 2006-10-27 2013-06-18 The Board Of Regents Of The University Of Texas System Methods and compositions related to wrapping of dehydrons
US8337883B2 (en) 2006-11-03 2012-12-25 Durect Corporation Transdermal delivery systems
EP2097450A2 (en) * 2006-11-10 2009-09-09 Amgen Inc. Antibody-based diagnostics and therapeutics
WO2008133722A2 (en) * 2006-11-10 2008-11-06 Ucb Pharma S.A. Anti human sclerostin antibodies
EP2567975A3 (en) 2006-11-21 2013-07-03 The Regents of The University of California Modulation of RHAMM (CD168) for selective adipose tissue development
BRPI0717721A2 (pt) 2006-11-28 2013-10-29 Marinus Pharmaceuticals "partículas complexadas de drogas, composição farmacêutica, uso de uma composição farmacêutica, partículas complexadas de droga estabilizadas no tamanho, método para a preparação de partículas estabilizadas da droga, composição farmacêutica sólida, comprimido oral ingerível e composição líquida em nanopartículas estabilizadas no tamanho"
WO2008065502A1 (en) * 2006-11-29 2008-06-05 Pfizer Products Inc. Pharmaceutical compositions based on a) nanoparticles comprising enteric polymers and b) casein
PE20081506A1 (es) 2006-12-12 2008-12-09 Infinity Discovery Inc Formulaciones de ansamicina
WO2008080047A2 (en) * 2006-12-23 2008-07-03 Baxter International Inc. Magnetic separation of fine particles from compositions
US9511075B2 (en) 2007-01-12 2016-12-06 The University Of Maryland, Baltimore Targeting NCCA-ATP channel for organ protection following ischemic episode
AU2008214095B2 (en) 2007-02-02 2014-07-10 Baylor College Of Medicine Compositions and methods for the treatment of metabolic disorders
WO2008098160A1 (en) 2007-02-09 2008-08-14 University Of Maryland, Baltimore Antagonists of a non-selective cation channel in neural cells
KR20080084528A (ko) 2007-03-15 2008-09-19 제네렉스 바이오테라퓨틱스 인크. 종양살상형 백시니아 바이러스 암 치료
MX351247B (es) * 2007-04-04 2017-10-05 Infectious Disease Res Institute Star Composiciones inmunogenicas que comprenden polipeptidos de mycobacterium tuberculosis y fusiones de los mismos.
US9725485B2 (en) 2012-05-15 2017-08-08 University Of Florida Research Foundation, Inc. AAV vectors with high transduction efficiency and uses thereof for gene therapy
EP2191001B1 (en) 2007-04-09 2016-06-08 University of Florida Research Foundation, Inc. Raav vector compositions having tyrosine-modified capsid proteins and methods for use
WO2008125940A2 (en) * 2007-04-17 2008-10-23 Pfizer Products Inc. Nanoparticles comprising non-crystalline drug
US20100080852A1 (en) * 2007-05-03 2010-04-01 Ronald Arthur Beyerinck Phamaceutical composition comprising nanoparticles and casein
WO2008135855A2 (en) * 2007-05-03 2008-11-13 Pfizer Products Inc. Nanoparticles comprising a cholesteryl ester transfer protein inhibitor and a nonionizable polymer
US8309129B2 (en) * 2007-05-03 2012-11-13 Bend Research, Inc. Nanoparticles comprising a drug, ethylcellulose, and a bile salt
CA2686756A1 (en) * 2007-05-11 2008-11-20 F. Hoffmann-La Roche Ag Pharmaceutical compositions for poorly soluble drugs
US20080293814A1 (en) * 2007-05-22 2008-11-27 Deepak Tiwari Concentrate esmolol
US8722736B2 (en) * 2007-05-22 2014-05-13 Baxter International Inc. Multi-dose concentrate esmolol with benzyl alcohol
US8426467B2 (en) * 2007-05-22 2013-04-23 Baxter International Inc. Colored esmolol concentrate
WO2008149230A2 (en) 2007-06-04 2008-12-11 Pfizer Products Inc. Nanoparticles comprising drug, a non-ionizable cellulosic polymer and tocopheryl polyethylene glycol succinate
ES2465216T3 (es) 2007-06-04 2014-06-05 Ben Gurion University Of The Negev Research And Development Authority Compuestos de triarilo y composiciones que comprenden los mismos
US8974827B2 (en) * 2007-06-04 2015-03-10 Bend Research, Inc. Nanoparticles comprising a non-ionizable cellulosic polymer and an amphiphilic non-ionizable block copolymer
CA2691199C (en) 2007-06-22 2017-09-12 Marc J. Simard Inhibitors of ncca-atp channels for therapy
EP2178518A2 (en) * 2007-07-13 2010-04-28 Bend Research, Inc Nanoparticles comprising ionizable, poorly water soluble cellulosic polymers
US9683256B2 (en) 2007-10-01 2017-06-20 Longhorn Vaccines And Diagnostics, Llc Biological specimen collection and transport system
US11041215B2 (en) 2007-08-24 2021-06-22 Longhorn Vaccines And Diagnostics, Llc PCR ready compositions and methods for detecting and identifying nucleic acid sequences
US10004799B2 (en) 2007-08-27 2018-06-26 Longhorn Vaccines And Diagnostics, Llc Composite antigenic sequences and vaccines
EP2185196B1 (en) 2007-08-27 2014-06-11 Longhorn Vaccines & Diagnostics, LLC Immunogenic compositions and methods
US20090130210A1 (en) * 2007-09-11 2009-05-21 Raheja Praveen Pharmaceutical compositions of sirolimus
CL2008002775A1 (es) * 2007-09-17 2008-11-07 Amgen Inc Uso de un agente de unión a esclerostina para inhibir la resorción ósea.
EP3020832A1 (en) 2007-10-01 2016-05-18 Longhorn Vaccines and Diagnostics, LLC Biological specimen collection and transport system and methods of use
US11041216B2 (en) 2007-10-01 2021-06-22 Longhorn Vaccines And Diagnostics, Llc Compositions and methods for detecting and quantifying nucleic acid sequences in blood samples
JP2011506319A (ja) 2007-12-06 2011-03-03 デュレクト コーポレーション 疼痛、関節炎症状、または慢性疾患に伴う炎症の治療に有用な方法
WO2009073215A1 (en) * 2007-12-06 2009-06-11 Bend Research, Inc. Pharmaceutical compositions comprising nanoparticles and a resuspending material
US9233078B2 (en) * 2007-12-06 2016-01-12 Bend Research, Inc. Nanoparticles comprising a non-ionizable polymer and an Amine-functionalized methacrylate copolymer
US20090238867A1 (en) * 2007-12-13 2009-09-24 Scott Jenkins Nanoparticulate Anidulafungin Compositions and Methods for Making the Same
WO2009079471A1 (en) 2007-12-14 2009-06-25 Amgen Inc. Method for treating bone fracture with anti-sclerostin antibodies
ES2509490T3 (es) * 2007-12-24 2014-10-17 Sun Pharma Advanced Research Company Limited Nanodispersión
US8865223B2 (en) * 2008-02-11 2014-10-21 Technion Research And Development Foundation Ltd. Beta-casein assemblies for mucosal delivery of therapeutic bioactive agents
US8865222B2 (en) * 2008-02-11 2014-10-21 Technion Research And Development Foundation Ltd. Beta-casein assemblies for enrichment of food and beverages and methods of preparation thereof
EP2252269A1 (en) * 2008-02-11 2010-11-24 Technion Research and Development Foundation, Ltd. Casein particles encapsulating therapeutically active agents and uses thereof
US8871276B2 (en) 2008-02-11 2014-10-28 Technion Research And Development Foundation Ltd. Beta-casein assemblies for mucosal delivery of therapeutic bioactive agents
WO2009117401A2 (en) * 2008-03-21 2009-09-24 Elan Pharama International Limited Compositions for site-specific delivery of imatinib and methods of use
US8258111B2 (en) 2008-05-08 2012-09-04 The Johns Hopkins University Compositions and methods related to miRNA modulation of neovascularization or angiogenesis
US20090311335A1 (en) * 2008-06-12 2009-12-17 Scott Jenkins Combination of a triptan and an nsaid
EP2309991B1 (en) * 2008-06-16 2019-03-06 Pfizer Inc Therapeutic polymeric nanoparticles comprising vinca alkaloids and methods of making and using same
CN106434576A (zh) 2008-06-26 2017-02-22 Atyr 医药公司 包含具有非常规生物活性的甘氨酰‑tRNA合成酶的组合物和方法
WO2010009075A1 (en) * 2008-07-14 2010-01-21 The University Of North Carolina At Chapel Hill Methods and compositions comprising crystalline nanoparticles of hydrophobic compounds
WO2010013224A2 (en) * 2008-07-31 2010-02-04 Santosh Kumar Kar Curcumin nanoparticles and methods of producing the same
CZ2008523A3 (cs) * 2008-08-29 2009-10-14 Fyzikální ústav AV CR, v.v.i. Zpusob prípravy hybridních nanocástic z aglomerátu nanocástic komplexních vícesložkových oxidu kovu
EP2719380A3 (en) 2008-09-16 2014-07-30 University of Maryland, Baltimore SUR1 inhibitors for therapy
US20100099775A1 (en) * 2008-10-17 2010-04-22 Alpharx Inc. Method for ameliorating of post-anesthetic recovery
US20100260844A1 (en) 2008-11-03 2010-10-14 Scicinski Jan J Oral pharmaceutical dosage forms
US8765817B1 (en) 2008-12-03 2014-07-01 Arrowhead Center, Inc. Selective inhibitors of EG5 motors and methods of use
US8349899B1 (en) 2008-12-03 2013-01-08 Arrowhead Center, Inc. Selective inhibitors of EG5 motors and methods of use
JP5739816B2 (ja) 2008-12-19 2015-06-24 バクスター・インターナショナル・インコーポレイテッドＢａｘｔｅｒ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｉｎｃｏｒｐ０Ｒａｔｅｄ Ｔｆｐｉインヒビターおよび使用法
DK3045043T3 (da) 2009-02-26 2020-08-03 Relmada Therapeutics Inc Orale farmaceutiske sammensætninger af 3-hydroxy-n-methylmorphinan med forlænget frigivelse og fremgangsmåde til anvendelse
US20120004185A1 (en) 2009-02-27 2012-01-05 Atyr Pharma, Inc. Polypeptide structural motifs associated with cell signaling activity
CN102428175A (zh) 2009-03-16 2012-04-25 盘古生物制药有限公司 包含具有非经典生物活性的组氨酰-tRNA合成酶剪接变异体的组合物及方法
CA2757289A1 (en) 2009-03-31 2010-10-21 Atyr Pharma, Inc. Compositions and methods comprising aspartyl-trna synthetases having non-canonical biological activities
EP2421559B1 (en) 2009-04-24 2016-07-20 Vanderbilt University Anti-tgf-beta induction of bone growth
WO2010135714A2 (en) 2009-05-22 2010-11-25 The Methodist Hospital Research Institute Methods for modulating adipocyte expression using microrna compositions
FR2945950A1 (fr) 2009-05-27 2010-12-03 Elan Pharma Int Ltd Compositions de nanoparticules anticancereuses et procedes pour les preparer
WO2010138539A2 (en) 2009-05-27 2010-12-02 Elan Pharma International Ltd. Reduction of flake-like aggregation in nanoparticulate active agent compositions
WO2010138263A2 (en) 2009-05-28 2010-12-02 University Of Massachusetts Novel aav 's and uses thereof
EP2442805A4 (en) 2009-06-19 2012-11-21 Sun Pharma Advanced Res Co Ltd NANODISPERSION OF A MEDICINE AND METHOD FOR PREPARING THE SAME
EP2451496B1 (en) 2009-07-10 2015-07-22 Boston Scientific Scimed, Inc. Use of nanocrystals for a drug delivery balloon
WO2011008737A2 (en) 2009-07-13 2011-01-20 The University Of North Carolina At Chapel Hill Engineered aerosol particles, and associated methods
EP3100610A1 (en) 2009-07-24 2016-12-07 Baylor College Of Medicine Methods of modulation of branched chain acids and uses thereof
HUE038708T2 (hu) 2009-09-14 2018-11-28 Sillajen Biotherapeutics Inc Onkolitikus vaccinia vírus kombinációs rákterápia
MX365946B (es) 2009-12-10 2019-06-19 Turnstone Lp Rabdovirus oncolitico.
US20110150885A1 (en) 2009-12-11 2011-06-23 Atyr Pharma, Inc. Aminoacyl trna synthetases for modulating hematopoiesis
EP2509625B1 (en) 2009-12-11 2015-01-28 Atyr Pharma, Inc. Histidyl trna synthetases for reducing inflammation
MX2012007055A (es) 2009-12-18 2012-10-15 Amgen Inc Agentes epitopes de enlace wise.
KR20120129927A (ko) 2010-01-27 2012-11-28 글락소 그룹 리미티드 변형된 투베르쿨로시스 항원
TWI438009B (zh) * 2010-02-19 2014-05-21 Teikoku Pharma Usa Inc 紫杉烷前－乳劑調配物及其製造與使用之方法
KR101948463B1 (ko) 2010-03-19 2019-02-14 박스알타 인코퍼레이티드 Tfpi 저해제 및 사용 방법
SG10201502759TA (en) 2010-04-23 2015-06-29 Univ Florida Raav-guanylate cyclase compositions and methods for treating leber's congenital amaurosis-1 (lca1)
WO2011133901A2 (en) 2010-04-23 2011-10-27 University Of Massachusetts Aav-based treatment of cholesterol-related disorders
CA2833908C (en) 2010-04-23 2021-02-09 University Of Massachusetts Cns targeting aav vectors and methods of use thereof
AU2011248625B2 (en) 2010-04-26 2017-01-05 Pangu Biopharma Limited Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-tRNA synthetase
EP2563381B1 (en) 2010-04-27 2017-08-09 aTyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of isoleucyl trna synthetases
CN103097524B (zh) 2010-04-28 2016-08-03 Atyr医药公司 与丙氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现
CN103118693B (zh) 2010-04-29 2017-05-03 Atyr 医药公司 与缬氨酰‑tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现
AU2011248490B2 (en) 2010-04-29 2016-11-10 Pangu Biopharma Limited Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Asparaginyl tRNA synthetases
CN102970990A (zh) 2010-05-03 2013-03-13 帝国制药美国公司 非水性紫杉烷前-乳剂制剂以及制备和使用该制剂的方法
WO2011140132A2 (en) 2010-05-03 2011-11-10 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-alpha-trna synthetases
CN103096925A (zh) 2010-05-03 2013-05-08 Atyr医药公司 与精氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现
ES2668207T3 (es) 2010-05-03 2018-05-17 Atyr Pharma, Inc. Descubrimiento innovador de composiciones terapéuticas, de diagnóstico y de anticuerpos relacionadas con fragmentos de proteínas de metionil-ARNt sintetasas
US9062302B2 (en) 2010-05-04 2015-06-23 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of p38 multi-tRNA synthetase complex
SG185465A1 (en) 2010-05-14 2012-12-28 Amgen Inc High concentration antibody formulations
CN103200953B (zh) 2010-05-14 2017-02-15 Atyr 医药公司 与苯丙氨酰‑β‑tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现
CN103096914B (zh) 2010-05-17 2015-08-12 Atyr医药公司 与亮氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现
AU2011258106B2 (en) 2010-05-27 2017-02-23 Pangu Biopharma Limited Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-tRNA synthetases
EP2575857B1 (en) 2010-06-01 2018-01-24 aTyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of lysyl-trna synthetases
WO2012021247A2 (en) 2010-07-12 2012-02-16 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-trna synthetases
US10865445B2 (en) 2010-08-18 2020-12-15 Fred Hutchinson Cancer Research Center Methods for alleviating facioscapulohumeral dystrophy (FSHD) by N siRNA molecule inhibiting the expression of DUX4-FL
WO2012027611A2 (en) 2010-08-25 2012-03-01 Atyr Pharma, Inc. INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF TYROSYL-tRNA SYNTHETASES
US20130345079A1 (en) 2010-10-27 2013-12-26 Infectious Disease Research Institute Mycobacterium tuberculosis antigens and combinations thereof having high seroreactivity
EA201390676A1 (ru) 2010-11-08 2013-11-29 Инфекшес Дизиз Рисерч Инститьют Вакцины, содержащие полипептиды неспецифической нуклеозидгидролазы и стерол 24-c-метилтрансферазы (smt), для лечения и диагностики лейшманиоза
BR112013017096A2 (pt) 2011-01-04 2020-09-01 Jennerex Inc. composição e métodos de indução de resposta citotóxica dependente de complemento mediado por anticorpo específico de tumor em animal tendo tumor, de geração de anticorpos in vivo, de inibição do crescimento ou morte de célula de câncer, para tratar indivíduo com câncer, para adaptar de terapia de câncer para indivíduo com câncer e para identificar antígeno específico de tumor
WO2012097093A2 (en) 2011-01-11 2012-07-19 Fate Therapeutics, Inc. Novel wnt compositions and therapeutic uses of such compositions
WO2012103328A1 (en) 2011-01-26 2012-08-02 The Methodist Hospital Research Institute Labeled, non- peptidic multivalent integrin alpha -v - beta - 3 antagonists, compositions containing them and their use
MY165507A (en) 2011-02-03 2018-03-28 Mirna Therapeutics Inc Synthetic mimics of mir-34
CN103459598B (zh) 2011-02-03 2016-08-10 米尔纳医疗股份有限公司 Mir-124的合成模拟物
WO2012110469A1 (en) 2011-02-17 2012-08-23 F. Hoffmann-La Roche Ag A process for controlled crystallization of an active pharmaceutical ingredient from supercooled liquid state by hot melt extrusion
EA201391248A1 (ru) 2011-03-01 2014-05-30 Эмджен Инк. Биспецифические связывающие агенты
EA029956B1 (ru) 2011-03-25 2018-06-29 Эмджен Инк. Кристаллы антител против склеростина и составы на их основе
LT3404041T (lt) 2011-04-19 2020-08-25 Amgen Inc. Osteoporozės gydymo būdas
EP2710037B1 (en) 2011-05-19 2019-07-31 The Regents of The University of Michigan Integrin alpha-2 binding agents and use thereof to inhibit cancer cell proliferation
WO2012170384A1 (en) 2011-06-06 2012-12-13 Chevron Phillips Chemical Company Lp Use of metallocene compounds for cancer treatment
US9364532B2 (en) 2011-06-08 2016-06-14 Children's Hospital Of Eastern Ontario Research Institute Inc. Compositions and methods for glioblastoma treatment
ES2710452T3 (es) 2011-06-10 2019-04-25 Bluebird Bio Inc Vectores de terapia génica para la adrenoleucodistrofia y la adrenomieloneuropatía
US20150030586A1 (en) 2011-06-21 2015-01-29 Sarah Ellen Warren Compositions and methods for the therapy and diagnosis of cancer
PL2734634T3 (pl) 2011-07-22 2020-03-31 The University Of Chicago Igf-1 do zastosowania do leczenia migreny
ES2667554T3 (es) 2011-08-04 2018-05-11 Amgen Inc. Método para el tratamiento de los defectos de espacio óseo
US9655905B2 (en) 2011-09-14 2017-05-23 King Abdullah University Of Science And Technology Treatment of sickle cell disease
US9644005B2 (en) 2011-09-21 2017-05-09 King Abdullah University Of Science And Technology Didemnin biosynthetic gene cluster in Tistrella mobilis
AU2011377617B2 (en) 2011-09-23 2018-03-08 Bluebird Bio, Inc. Improved gene therapy methods
WO2013095736A2 (en) 2011-09-27 2013-06-27 The Methodist Hospital Research Institute Gold-in-silicon nanoassembly for thermal therapy and methods of use
ES2769270T3 (es) 2011-09-30 2020-06-25 Bluebird Bio Inc Compuestos para transducción viral mejorada
KR102110794B1 (ko) 2011-10-31 2020-05-15 더 메서디스트 하스피틀 리서치 인스티튜트 인간의 신경교종을 치료하기 위한 모노아마이드 옥시다아제(Monoamide oxidase,MAO) 타겟팅/시커(seeker) 부분(moiety)을 포함하는 조성물
US10208086B2 (en) 2011-11-11 2019-02-19 Fred Hutchinson Cancer Research Center Cyclin A1-targeted T-cell immunotherapy for cancer
JP2015501802A (ja) 2011-11-17 2015-01-19 ザ リージェンツ オブ ザ ユニバーシティ オブ コロラド，ア ボディー コーポレイトＴＨＥ ＲＥＧＥＮＴＳ ＯＦ ＴＨＥ ＵＮＩＶＥＲＳＩＴＹ ＯＦ ＣＯＬＯＲＡＤＯ，ａ ｂｏｄｙ ｃｏｒｐｏｒａｔｅ 眼への薬物送達を向上させるための方法および組成物、ならびに徐放性送達製剤
US20130177627A1 (en) * 2011-11-18 2013-07-11 Linda Einbond Growth inhibitory effects of nanoparticles containing triterpene glycosides or triterpenes
US9546367B2 (en) 2011-12-07 2017-01-17 Jenny Chee Ning Chang siRNA compositions and methods for inhibiting gene expression in tumor initiating cells of breast cancer
BR112014016108A2 (pt) 2011-12-28 2018-09-11 Amgen Inc método de tratamento de perda óssea alvelar
CN104203272A (zh) 2012-01-26 2014-12-10 长角牛疫苗和诊断有限责任公司 复合抗原序列及疫苗
US20150024037A1 (en) 2012-02-16 2015-01-22 The University Of Toledo Xenoantigen-Displaying Anti-Cancer Vaccines and Method of Making
NZ629130A (en) 2012-03-21 2016-10-28 Baxalta Inc Tfpi inhibitors and methods of use
US20140128431A1 (en) 2012-04-03 2014-05-08 Hoffmann-Laroche Inc. Pharmaceutical composition with improved bioavailability, safety and tolerability
AR092821A1 (es) 2012-04-20 2015-05-06 Sucampo Ag Conjugado de derivado de acido graso-polimero
EP2852380A4 (en) 2012-05-23 2016-01-20 Univ Ohio State LIPID-COATED ALBUMIN NANOPARTICLE COMPOSITIONS AND METHOD FOR THE PREPARATION AND METHOD OF USE THEREOF
EP3626267A1 (en) 2012-07-05 2020-03-25 UCB Pharma, S.A. Treatment for bone diseases
WO2014039189A1 (en) 2012-08-01 2014-03-13 Mcnally Elizabeth Mitigating tissue damage and fibrosis via latent transforming growth factor beta binding protein (ltbp4)
BR112015002483A2 (pt) 2012-08-03 2017-11-07 Infectious Disease Res Inst composições e métodos para o tratamento de uma infecção ativa por mycobacterium tuberculosis
JO3685B1 (ar) 2012-10-01 2020-08-27 Teikoku Pharma Usa Inc صيغ التشتيت الجسيمي للتاكسين غير المائي وطرق استخدامها
UY35148A (es) 2012-11-21 2014-05-30 Amgen Inc Immunoglobulinas heterodiméricas
CN104936589A (zh) 2013-01-22 2015-09-23 霍夫曼-拉罗奇有限公司 具有改善的生物利用度的药物组合物
SG11201505960VA (en) 2013-02-01 2015-08-28 Santa Maria Biotherapeutics Inc Administration of an anti-activin-a compound to a subject
RU2684211C2 (ru) 2013-02-21 2019-04-04 Тёрнстоун Лимитед Партнершип Композиция вакцины
US10208012B2 (en) 2013-03-13 2019-02-19 Board Of Regents, The University Of Texas System Compounds for treating inflammatory and hyperproliferative diseases
US9572885B2 (en) 2013-03-15 2017-02-21 Durect Corporation Compositions with a rheological modifier to reduce dissolution variability
WO2014160987A2 (en) 2013-03-28 2014-10-02 Infectious Disease Research Institute Vaccines comprising leishmania polypeptides for the treatment and diagnosis of leishmaniasis
US9393202B2 (en) * 2013-04-26 2016-07-19 Chiesi Farmaceutici S.P.A Particle size reduction of an antimuscarinic compound
WO2014186746A1 (en) 2013-05-16 2014-11-20 University Of Florida Research Foundation, Inc. HAIRPIN mRNA ELEMENTS AND METHODS FOR THE REGULATION OF PROTEIN TRANSLATION
CR20160207A (es) 2013-11-05 2016-08-10 Ben Gurion Univ Of The Negev Res And Dev Authority Compuestos para el tratamiento de la diabetes y las complicaciones que surgen de la misma enfermedad
WO2015084625A1 (en) 2013-12-02 2015-06-11 Baylor College Of Medicine Identification of a new polypeptide hormone for maintenance of optimal body weight and blood glucose
CN110845615B (zh) 2014-03-21 2023-10-20 艾伯维公司 抗-egfr抗体及抗体药物偶联物
KR20160143775A (ko) 2014-04-08 2016-12-14 더 메서디스트 하스피틀 iNOS-억제 조성물들 및 이들의 유방암 치료제로서의 용도
WO2015157500A1 (en) 2014-04-09 2015-10-15 Research Development Foundation Class iia hdac inhibitors for the treatment of infection
WO2015164786A1 (en) 2014-04-25 2015-10-29 University Of Massachusetts Recombinant aav vectors useful for reducing immunity against transgene products
MX2016016826A (es) 2014-06-20 2017-08-28 Aveo Pharmaceuticals Inc Tratamiento de la enfermedad renal cronica y otra disfuncion renal utilizando un modulador gdf15.
EP3157952B1 (en) 2014-06-20 2021-12-22 Aveo Pharmaceuticals, Inc. Treatment of congestive heart failure and other cardiac dysfunction using a gdf15 modulator
US10278986B2 (en) 2014-08-14 2019-05-07 The Regents Of The University Of Colorado, A Body Corporate Antibody-siRNA conjugates and uses therefor
JP2017532013A (ja) 2014-09-01 2017-11-02 アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ 寿命に関する動物モデル並びに寿命を延ばす及び腫瘍化を阻害する関連方法
EP3189143B1 (en) 2014-09-04 2019-08-07 Memorial Sloan-Kettering Cancer Center Globin gene therapy for treating hemoglobinopathies
HUE054670T2 (hu) 2014-09-25 2021-09-28 Aveo Pharmaceuticals Inc Módszer cachexia visszafordítására és túlélés megnövelésére egy GDF15 modulátor és egy rákellenes szer adagolásával
US10711270B2 (en) 2014-10-03 2020-07-14 University Of Massachusetts High efficiency library-identified AAV vectors
RU2738421C2 (ru) 2014-10-21 2020-12-14 Юниверсити Оф Массачусетс Варианты рекомбинантных aav и их применения
US10302644B2 (en) 2014-11-04 2019-05-28 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating multiple myeloma
MA41142A (fr) 2014-12-12 2017-10-17 Amgen Inc Anticorps anti-sclérostine et utilisation de ceux-ci pour traiter des affections osseuses en tant qu'élements du protocole de traitement
CA2967468A1 (en) 2014-12-16 2016-06-23 Board Of Regents Of The University Of Nebraska Gene therapy for juvenile batten disease
US10166197B2 (en) 2015-02-13 2019-01-01 St. John's University Sugar ester nanoparticle stabilizers
MX2017011615A (es) 2015-03-10 2018-04-11 Univ Columbia Construcciones de vectores virales adeno-asociados de glut1 recombinantes y métodos relacionados para restablecer la expresión de glut1.
WO2016172026A1 (en) 2015-04-20 2016-10-27 The Board Of Regents Of The University Of Texas System Clec11a is a bone growth agent
EP3288957A4 (en) 2015-05-01 2019-01-23 Cocrystal Pharma, Inc. NUCLEOSIDE ANALOGUE FOR THE TREATMENT OF VIRUSES OF THE FLAVIVIIDAE FAMILY AND CANCER
EP3294448A4 (en) 2015-05-14 2018-12-12 Longhorn Vaccines and Diagnostics, LLC Rapid methods for the extraction of nucleic acids from biological samples
DK3302431T3 (da) * 2015-06-04 2020-11-30 Crititech Inc Taxanpartikler og anvendelse deraf
WO2016205615A1 (en) 2015-06-17 2016-12-22 The Johns Hopkins University Tdp-43 in degenerative disease
CA2998483C (en) 2015-09-16 2022-09-06 Dfb Soria, Llc Delivery of drug nanoparticles and methods of use thereof
EP3357396B1 (en) * 2015-09-28 2019-11-06 Sumitomo Osaka Cement Co., Ltd. Method for manufacturing dishwasher/dryer
WO2017066626A1 (en) 2015-10-16 2017-04-20 Marinus Pharmaceuticals, Inc. Injectable neurosteroid formulations containing nanoparticles
EP3364997B1 (en) 2015-10-22 2024-01-17 University of Massachusetts Aspartoacylase gene therapy in the treatment of canavan disease
KR20180104597A (ko) 2015-11-07 2018-09-21 멀티비르 인코포레이티드 암 치료를 위한 종양 억제 유전자 요법 및 면역관문 봉쇄를 포함하는 조성물
KR20180136435A (ko) 2016-01-27 2018-12-24 온코루스, 인크. 종양 살상형 바이러스 벡터 및 그의 용도
US10695322B2 (en) 2016-01-29 2020-06-30 The Johns Hopkins University Inhibitors of bacterial growth
WO2017139643A1 (en) 2016-02-12 2017-08-17 University Of Massachusetts Anti-angiogenic mirna therapeutics for inhibiting corneal neovascularization
WO2017143112A2 (en) 2016-02-17 2017-08-24 The Johns Hopkins University An oxazolidinone for treatment of infections with mycobacterium tuberculosis
WO2017147215A1 (en) 2016-02-22 2017-08-31 The Methodist Hospital Biomimetic proteolipid vesicle compositions and uses thereof
WO2017147370A1 (en) 2016-02-24 2017-08-31 The Johns Hopkins University Novel antiviral proteins and their uses in therapeutic methods
AU2017225769B2 (en) 2016-03-02 2023-01-05 The Board Of Regents Of The University Of Texas System Sting activating nanovaccine for immunotherapy
HRP20211697T1 (hr) 2016-03-03 2022-02-04 University Of Massachusetts Zatvorena linearna dupleks dnk za nevirusni prijenos gena
WO2017155935A1 (en) 2016-03-07 2017-09-14 The Johns Hopkins University Pharmaceutical agents targeting cancer stem cells
GB201604124D0 (en) 2016-03-10 2016-04-27 Ucb Biopharma Sprl Pharmaceutical formulation
CN109790545A (zh) 2016-03-10 2019-05-21 约翰·霍普金斯大学 产生不含聚集物的单体白喉毒素融合蛋白的方法和治疗用途
US11203626B2 (en) 2016-03-10 2021-12-21 The Johns Hopkins University Methods of producing aggregate-free monomeric diphtheria toxin fusion proteins and therapeutic uses
WO2017161155A1 (en) 2016-03-17 2017-09-21 The Johns Hopkins University Methods for preventing or treating parkinson's disease by the farnesylation of paris
EP3436609B1 (en) 2016-03-30 2022-05-04 The Johns Hopkins University Olfr90 specificity and methods of detection
CA3018989A1 (en) 2016-04-04 2017-10-12 Crititech, Inc. Methods for solid tumor treatment
US11016085B2 (en) 2016-04-25 2021-05-25 The Johns Hopkins University ZNT8 assays for drug development and pharmaceutical compositions
JP2019521095A (ja) 2016-05-21 2019-07-25 インフェクシャス ディズィーズ リサーチ インスティチュート 二次性結核および非結核性マイコバクテリウム感染症を治療するための組成物および方法
TW202304996A (zh) 2016-06-08 2023-02-01 美商艾伯維有限公司 抗-b7-h3抗體及抗體藥物結合物
BR112018075644A2 (pt) 2016-06-08 2019-04-09 Abbvie Inc. anticorpos anti-cd98 e conjugados de anticorpo e fármaco
US20200002421A1 (en) 2016-06-08 2020-01-02 Abbvie Inc. Anti-b7-h3 antibodies and antibody drug conjugates
MX2018015274A (es) 2016-06-08 2019-10-07 Abbvie Inc Anticuerpos anti-cd98 y conjugados de anticuerpo y farmaco.
EP3469000A1 (en) 2016-06-08 2019-04-17 AbbVie Inc. Anti-b7-h3 antibodies and antibody drug conjugates
MX2019000221A (es) 2016-07-05 2020-02-07 Univ Massachusetts Suministro genetico de sfasl mediado por aav2 como una terapia neuro-protectora en el glaucoma.
AU2017298385A1 (en) 2016-07-19 2019-03-07 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Oncolytic viruses targeting STAT3
CN109715151A (zh) 2016-08-11 2019-05-03 奥维德医疗公司 用于治疗癫痫性紊乱的方法和组合物
US9963498B2 (en) 2016-08-18 2018-05-08 Wisconsin Alumni Research Foundation Peptides that inhibit syndecan-1 activation of VLA-4 and IGF-1R
US10391105B2 (en) 2016-09-09 2019-08-27 Marinus Pharmaceuticals Inc. Methods of treating certain depressive disorders and delirium tremens
MX2019003035A (es) 2016-09-16 2019-09-13 Infectious Disease Res Inst Vacunas que comprenden polipeptidos de mycobacterium leprae para la prevencion, el tratamiento y el diagnostico de la lepra.
US10457940B2 (en) 2016-09-22 2019-10-29 University Of Massachusetts AAV treatment of Huntington's disease
US11149275B2 (en) 2016-10-10 2021-10-19 The Johns Hopkins University Device and method to treat esophageal disorders
AU2017341849B2 (en) 2016-10-13 2024-03-21 University Of Massachusetts AAV capsid designs
CA3043160A1 (en) 2016-11-08 2018-05-17 University Of Miami Anti-secretogranin iii (scg3) antibodies and uses thereof
US20200009203A1 (en) 2016-12-12 2020-01-09 Multivir Inc. Methods and compositions comprising viral gene therapy and an immune checkpoint inhibitor for treatment and prevention of cancer and infectious diseases
US10434089B2 (en) 2017-01-25 2019-10-08 The Johns Hopkins University Avibactam and carbapenems antibacterial agents
DK4008344T3 (da) 2017-01-27 2024-01-29 Methodist Hospital Kerne/skal struktur platform til immunterapi
CA3053309A1 (en) 2017-02-12 2018-08-16 Ben-Gurion University Of The Negev Research And Development Authority Telomerase activating compounds for use in fertility and related applications
WO2018170196A1 (en) 2017-03-15 2018-09-20 Dfb Soria, Llc Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes
AU2018261637A1 (en) 2017-05-03 2019-12-12 Biomarin Pharmaceutical Inc. Improved lentiviruses for transduction of hematopoietic stem cells.
US11680275B2 (en) 2017-06-06 2023-06-20 University Of Massachusetts Self-regulating AAV vectors for safe expression of MeCP2 in rett syndrome
JP2020523285A (ja) 2017-06-09 2020-08-06 クリチテック，インコーポレイテッド 抗腫瘍粒子の嚢胞内注入による上皮嚢胞の治療
JP6840869B2 (ja) * 2017-06-14 2021-03-10 クリチテック，インコーポレイテッド 肺障害の治療方法
US11892457B2 (en) 2017-07-12 2024-02-06 The Johns Hopkins University Proteoliposome-based ZnT8 self-antigen for type 1 diabetes diagnosis
AU2018306455A1 (en) 2017-07-26 2020-02-27 Virogin Biotech Canada Ltd Oncolytic viral vectors and uses thereof
WO2019028469A1 (en) 2017-08-04 2019-02-07 The Methodist Hospital FUNCTIONALIZED POLYMER MITOCHONDRIAL COMPOSITIONS AND METHODS OF USE IN CELL TRANSPLANTATION AND FOR MODIFYING METABOLIC PHENOTYPE
CN111315406A (zh) 2017-09-08 2020-06-19 传染病研究所 包括皂苷的脂质体调配物及其使用方法
EP3691631A1 (en) 2017-10-03 2020-08-12 Crititech, Inc. Local delivery of antineoplastic particles in combination with systemic delivery of immunotherapeutic agents for the treatment of cancer
WO2019099613A1 (en) 2017-11-16 2019-05-23 University Of Maine System Board Of Trustees Compositions and methods for modulating endothelial cell migration and angiogenesis
EP3720509A4 (en) 2017-12-06 2021-12-08 Memorial Sloan-Kettering Cancer Center GLOBING THERAPY FOR THE TREATMENT OF HEMOGLOBINOPATHIES
WO2019134049A1 (en) 2018-01-05 2019-07-11 Bell John C Modified vaccinia vectors
US11497726B2 (en) 2018-03-16 2022-11-15 Dfb Soria, Ll. Topical therapy for the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer using nanoparticles of taxanes
KR20200135986A (ko) 2018-03-19 2020-12-04 멀티비르 인코포레이티드 종양 억제인자 유전자 치료 및 cd122/cd132 작용제를 포함하는 암 치료를 위한 방법 및 조성물
CN112368051A (zh) 2018-03-23 2021-02-12 马萨诸塞大学 用于治疗骨病的基因治疗剂
MX2020010092A (es) 2018-03-30 2020-10-28 Amgen Inc Variantes de anticuerpo c-terminales.
US11472848B2 (en) 2018-04-27 2022-10-18 University Of Massachusetts AAV capsids identified by in vivo library selection
SG11202009914SA (en) 2018-05-08 2020-11-27 Rutgers The State University Of New Jersey Aav-compatible laminin-linker polymerization proteins
KR102167755B1 (ko) 2018-05-23 2020-10-19 주식회사 큐어바이오 단편화된 grs 폴리펩타이드, 이의 변이체 및 이들의 용도
MX2021003663A (es) 2018-09-28 2021-05-28 Harvard College Reprogramacion celular para revertir el envejecimiento y promover la regeneracion de organos y tejidos.
CA3113470A1 (en) 2018-09-28 2020-04-02 President And Fellows Of Harvard College Mutant reverse tetracycline transactivators for expression of genes
WO2020112967A1 (en) 2018-11-29 2020-06-04 University Of Massachusetts Modulation of sptlc1 via recombinant adeno-associated vectors
WO2020118142A1 (en) 2018-12-07 2020-06-11 Marinus Pharmaceuticals, Inc. Ganaxolone for use in prophylaxis and treatment of pospartum depression
WO2020114615A1 (en) 2018-12-07 2020-06-11 Baxalta GmbH Bispecific antibodies binding factor ixa and factor x
WO2020115283A1 (en) 2018-12-07 2020-06-11 Baxalta GmbH Bispecific antibodies binding factor ixa and factor x
AU2019406214A1 (en) 2018-12-21 2021-08-05 Northwestern University Use of annexins in preventing and treating muscle membrane injury
WO2020139977A1 (en) 2018-12-26 2020-07-02 Northwestern University Use of glucocorticoid steroids in preventing and treating conditions of muscle wasting, aging and metabolic disorder
US20220088221A1 (en) 2019-01-12 2022-03-24 The Methodist Hospital Self-assembled peptide nanoparticle and use thereof
WO2020163766A1 (en) 2019-02-07 2020-08-13 Baylor College Of Medicine Periosteal skeletal stem cells in bone repair
CA3131023A1 (en) 2019-02-22 2020-08-27 Michael R. Volkert Oxr1 gene therapy
US11717506B2 (en) 2019-05-07 2023-08-08 The Johns Hopkins University Neuroprotective compounds for amyotrophic lateral sclerosis
EP4009982A4 (en) 2019-08-05 2023-08-09 Marinus Pharmaceuticals, Inc. GANAXOLONE FOR USE IN THE TREATMENT OF STATUS EPILEPTICUS
CN114555814A (zh) 2019-09-13 2022-05-27 罗特格斯新泽西州立大学 Aav相容的层粘连蛋白-连接子聚合蛋白
CA3157063A1 (en) 2019-10-10 2021-04-15 Oncorus, Inc. Dual viruses and dual oncolytic viruses and methods of treatment
WO2021113644A1 (en) 2019-12-05 2021-06-10 Multivir Inc. Combinations comprising a cd8+ t cell enhancer, an immune checkpoint inhibitor and radiotherapy for targeted and abscopal effects for the treatment of cancer
AU2020395254A1 (en) 2019-12-06 2022-06-02 Marinus Pharmaceuticals, Inc. Ganaxolone for use in treating tuberous sclerosis complex
CN115666621A (zh) 2020-01-13 2023-01-31 度勒科特公司 具有减少的杂质的持续释放药物递送系统及相关方法
KR20220144377A (ko) 2020-01-30 2022-10-26 우모자 바이오파마 인코포레이티드 이중특이적 형질도입 촉진제
AU2021248577A1 (en) 2020-03-31 2022-09-29 Sichuan Univeristy AAV capsids variants and uses thereof
MX2023001586A (es) 2020-08-07 2023-05-03 Access To Advanced Health Inst Saponinas purificadas y proceso cromatografico para purificacion de las mismas.
KR20230117177A (ko) 2020-12-03 2023-08-07 유니버시티 오브 매사추세츠 진행성 골화성 섬유이형성증을 위한 신규 유전자 치료제의개발
KR20220082558A (ko) 2020-12-10 2022-06-17 재단법인 의약바이오컨버젼스연구단 면역 증진 활성이 있는 신규 crs 단편 펩타이드 및 이의 용도
AR124681A1 (es) 2021-01-20 2023-04-26 Abbvie Inc Conjugados anticuerpo-fármaco anti-egfr
JP2024505887A (ja) 2021-01-27 2024-02-08 ウモジャ バイオファーマ， インコーポレイテッド 抗ｃｄ１９キメラ抗原受容体を発現する細胞を生成するためのレンチウイルス
WO2023092060A1 (en) 2021-11-18 2023-05-25 Cornell University Microrna-dependent mrna switches for tissue-specific mrna-based therapies
GB2614309A (en) 2021-12-24 2023-07-05 Stratosvir Ltd Improved vaccinia virus vectors
WO2023144393A1 (en) 2022-01-28 2023-08-03 Fundació Centre De Regulació Genòmica Therapeutic cytokines and methods
WO2023196851A1 (en) 2022-04-06 2023-10-12 President And Fellows Of Harvard College Reversing aging of the central nervous system
WO2023225569A1 (en) 2022-05-17 2023-11-23 Umoja Biopharma, Inc. Manufacturing viral particles

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2671750A (en) * 1950-09-19 1954-03-09 Merck & Co Inc Stable noncaking aqueous suspension of cortisone acetate and method of preparing the same
JPS4932056B1 (zh) * 1970-12-22 1974-08-27
US4107288A (en) * 1974-09-18 1978-08-15 Pharmaceutical Society Of Victoria Injectable compositions, nanoparticles useful therein, and process of manufacturing same
DK143689C (da) * 1975-03-20 1982-03-15 J Kreuter Fremgangsmaade til fremstilling af en adsorberet vaccine
DE3013839A1 (de) * 1979-04-13 1980-10-30 Freunt Ind Co Ltd Verfahren zur herstellung einer aktivierten pharmazeutischen zusammensetzung
FR2504408B1 (fr) * 1981-04-24 1986-02-14 Couvreur Patrick Procede de preparation de particules submicroscopiques, particules ainsi obtenues et compositions pharmaceutiques les contenant
SE8204244L (sv) * 1982-07-09 1984-01-10 Ulf Schroder Kristalliserad kolhydratsmatris for biologiskt aktiva substanser
CA1282405C (en) * 1984-05-21 1991-04-02 Michael R. Violante Method for making uniformly sized particles from water-insoluble organic compounds
US4826689A (en) * 1984-05-21 1989-05-02 University Of Rochester Method for making uniformly sized particles from water-insoluble organic compounds
CA1264566A (en) * 1984-09-05 1990-01-23 Tetsuji Iwasaki Biocidal fine powder, its manufacturing method and a suspension for agricultural use containing the above powder
GB8601100D0 (en) * 1986-01-17 1986-02-19 Cosmas Damian Ltd Drug delivery system
JPS62185013A (ja) * 1986-02-08 1987-08-13 Green Cross Corp:The 易吸収性医薬組成物
JPS6479154A (en) * 1986-09-29 1989-03-24 Green Cross Corp Benzoylurea compound
EP0262560A3 (en) * 1986-09-29 1989-07-05 Ishihara Sangyo Kaisha, Ltd. Benzoyl urea compound
NL194638C (nl) * 1986-12-19 2002-10-04 Novartis Ag Hydrosol die vaste deeltjes van een farmaceutisch actieve stof bevat en farmaceutisch preparaat dat deze hydrosol bevat.
FR2608988B1 (fr) * 1986-12-31 1991-01-11 Centre Nat Rech Scient Procede de preparation de systemes colloidaux dispersibles d'une substance, sous forme de nanoparticules
FR2634397B2 (fr) * 1986-12-31 1991-04-19 Centre Nat Rech Scient Procede de preparation de systemes colloidaux dispersibles d'une proteine sous forme de nanoparticules
FR2608942B1 (fr) * 1986-12-31 1991-01-11 Centre Nat Rech Scient Procede de preparation de systemes colloidaux dispersibles d'une substance, sous forme de nanocapsules
IT1227626B (it) * 1988-11-28 1991-04-23 Vectorpharma Int Farmaci supportati aventi velocita' di dissoluzione aumentata e procedimento per la loro preparazione
JP2773895B2 (ja) * 1989-04-25 1998-07-09 東京田辺製薬株式会社 ダナゾール組成物
GB8914060D0 (en) * 1989-06-19 1989-08-09 Wellcome Found Agents for potentiating the effects of antitumour agents and combating multiple drug resistance
SE464743B (sv) * 1989-06-21 1991-06-10 Ytkemiska Inst Foerfarande foer framstaellning av laekemedelspartiklar
JP2642486B2 (ja) * 1989-08-04 1997-08-20 田辺製薬株式会社 難溶性薬物の超微粒子化法
JP2687245B2 (ja) * 1989-09-29 1997-12-08 富士写真フイルム株式会社 磁気記録媒体の製造方法
GB8923075D0 (en) * 1989-10-13 1989-11-29 Patterson Laurence H Anti-cancer compounds
DK546289D0 (da) * 1989-11-02 1989-11-02 Danochemo As Carotenoidpulvere
FR2660556B1 (fr) * 1990-04-06 1994-09-16 Rhone Poulenc Sante Microspheres, leur procede de preparation et leur utilisation.
US5091188A (en) * 1990-04-26 1992-02-25 Haynes Duncan H Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs
US5145684A (en) * 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
AU642066B2 (en) * 1991-01-25 1993-10-07 Nanosystems L.L.C. X-ray contrast compositions useful in medical imaging
ATE150297T1 (de) * 1992-06-10 1997-04-15 Nanosystems Llc Oberflaechenmodifizierte nsaid nanopartikeln
US5298262A (en) * 1992-12-04 1994-03-29 Sterling Winthrop Inc. Use of ionic cloud point modifiers to prevent particle aggregation during sterilization
US5302401A (en) * 1992-12-09 1994-04-12 Sterling Winthrop Inc. Method to reduce particle size growth during lyophilization

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AU4156093A (en) 1994-01-06
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