CN112585690A - 用于制作含有药物活性物质的个性化个体单位剂量的系统和方法 - Google Patents
用于制作含有药物活性物质的个性化个体单位剂量的系统和方法 Download PDFInfo
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Abstract
描述了用于针对个体患者制作和递送个性化的医学处方药物的系统和方法。可以通过以下方式来制备针对需要治疗的个体具特异性的药物的个体单位剂量(IUD):使用如下系统,所述系统包括网络化控制系统与针对所述IUD具特异性的制造组件的组合;以及将所述药物直接从所述制造商递送给所述患者。
Description
相关申请的交叉引用
本申请要求于2018年6月21日提交的美国临时专利申请号62/688,107、于2018年7月19日提交的美国临时专利申请号62/700,444和于2018年9月10日提交的美国临时专利申请号62/729,051的优先权,这些美国临时专利申请的内容以引用方式整体并入本文。
技术领域
本公开涉及用于制作个性化个体单位剂量(IUD)以向个体递送规定量的活性物质的系统和方法。具体地,本公开涉及根据个体的关于特定活性物质的处方定制IUD的制造并将所制造的IUD递送给患者的方法。
背景技术
目前,IUD是以各种形式可得的,该各种形式包括片剂、囊片、胶囊剂、糯米纸囊剂(wafer)、膜剂、片层、注射笔、乳膏剂、软膏剂、凝胶剂和注射器等。IUD通常由药品制造商制造,并且含有根据政府批准的量和针对政府批准的适应症的剂量的一种或多种活性物质。通常,由医疗专业人员对个体患者(人类或其他动物)进行评定,并开具针对特定治疗方案的处方。处方限于政府批准并且因此商购可得的剂量。患者将处方提供给执业的处方填写者,诸如药房,所述处方填写者持有从制造商处购买的IUD库存。处方填写者执行个体患者的处方。在一些情况下,将处方直接从医疗专业人员传达给处方填写者。在其他情况下,将IUD从处方填写者邮寄给患者。
当前,处方是按照政府批准的剂量量执行的,所述政府批准的剂量量在大多数情况下对于患者而言是足够的,但并非总是医疗专业人员认为适合所述患者的量,例如关于药品核准标示外使用(off-label use)。例如,医疗专业人员可通知患者将IUD切成两半,以便在任何一次仅服用活性物质的一半(或一些其他部分)。可替代地,医疗专业人员可以指示患者服用比特定治疗的批准量更大的剂量。在一些情况下,医疗专业人员可针对与特定活性物质所批准用于的医学适应症不同的医学适应症开具所述活性物质和剂量的处方。目前,此类药品核准标示外使用和剂量变化是在逐患者的基础上进行的,但是执行处方的当前方法缺乏的是针对特定个体定制(个性化)特定IUD,以及更有效并且更具成本效益的生产针对个体患者的医疗需求个性化的IUD的方式。另外,目前,药房主要是IUD的配药者,但是一些药房是执业配制人员,因此被允许提供药物的某些配混(包括活性物质在内的成分的组合),特别是当要将两种或更多种药物(活性物质)掺入处方时。一般而言,配混是指执业药师、执业医师、或者在外包设施的情况下在执业药师的监督下的人员将药物成分组合、混合或进行更改以创建针对个体患者的需求定制的药物的实践。由于缺乏制造设备、工艺知识、质量控制、制造设施和专门知识,由药剂师进行配混具有明显的局限性。有时,FDA批准的药物无法满足患者的健康需求,例如,如果患者患有过敏症并且需要药物在没有某种组分(例如染料)的情况下制备时;或者如果老年患者或儿童无法吞服药丸并且需要药物为液体形式否则不可用时。此外,配混药物未经FDA批准。这意味着FDA无法验证配混药物的安全性或有效性。消费者和医疗专业人员依靠药品批准程序来确保药品安全有效并且是根据联邦质量标准制造的。在此类药物投放市场之前,配混药物还缺乏FDA对制造质量的认定。
需要用于制造订购的个性化IUD的系统,该系统高效、成本更低并且维持政府机构当前要求的良好制造和质量控制标准。还需要用于制造订购的个性化IUD的系统和方法,该系统和方法减少或减轻库存,从而进一步减少开销和与其相关的成本。
发明内容
公开了一种用于创建一个或多个个性化个体单位剂量(IUD)的系统,该一个或多个个性化IUD包含用于治疗个体的规定量的活性物质。该系统包括:用于制造个性化IUD的装置;以及网络化系统,该网络化系统被配置为以电子方式传送从该个体测量的健康信息。该装置用于根据医疗处方制造该IUD并且选自由以下组成的组:成膜组件、胶囊填写组件、片剂成形组件、片剂包衣组件、共混(混合)组件、粉末成形组件、制粒组件、喷雾干燥组件、挤出机组件、配混组件、包装组件、贴标签组件、压花组件、刻痕组件、质量控制组件,以及它们的组合。将健康信息以电子方式传送给医疗专业人员,该医疗专业人员确定医疗处方,该医疗处方包括个性化IUD中的活性物质的规定量。网络化系统可包括处理器、记忆存储器和可执行指令;以及显示设备、字母数字输入设备、光标控制设备、驱动单元、机器可读介质和信号生成设备中的至少一者。该系统还可包括生物特征测量模块,该生物特征测量模块与个体对接。该生物特征测量模块可包括侵入式设备和/或非侵入式测量设备,或它们的组合。
在本公开的另一方面中,提供了一种针对个体生产含有活性物质的个性化IUD的方法。该方法包括:a)获得与该个体的健康有关的生物特征测量结果;b)将该生物特征测量结果传输给医疗或处方产品的制造商;c)根据特定于该个体的医疗处方制造IUD;以及d)将根据该医疗处方制成的IUD递送给该个体。该方法还可包括在制造IUD的步骤之前将该个体的生物特征测量结果电子传输给被授权书写医疗处方的医疗专业人员,和/或将该医疗处方电子传输给制造商的步骤。制造IUD可包括使用装置和/或将活性物质添加到载体基质中。制造IUD可包括在一个或多个单独孔中形成IUD和/或将活性物质添加到已经形成的IUD中的步骤。IUD可为膜剂、糯米纸囊剂、胶囊剂、片剂、混悬剂、溶液剂、软膏剂、贴剂、乳膏剂、凝胶剂、锭剂、安瓿、药瓶、糖浆剂、酊剂、醑剂、锭剂、芳香制剂、搽剂、注射剂,或它们的任何组合。当IUD为膜剂时,它可为单层或多层的。活性物质可在第一膜层、第二膜层或两者中。活性物质可选自由以下组成的组:小分子、大分子、生物制品、微生物、过敏原、酶,以及它们的组合。
另一个方面是一种用于创建一个或多个含有规定量的活性物质的个性化个体单位剂量(IUD)以分发和施用给个体的方法。该方法包括以下步骤:(a)向医疗专业人员提供该个体的个人健康信息;(b)由该医疗专业人员开医疗处方,该医疗处方包括至少部分根据该个人健康信息确定的要施用给该个体的活性物质的量,该医疗处方包括用于每个性化个体单位剂量(IUD)施用规定量的活性物质的治疗方案;(c)将该医疗处方的至少部分电子传送给IUD的制造商;(c)使用用于制造个性化IUD的装置制造该IUD;以及(d)将该IUD分发给该个体。
根据以下具体实施方式,所公开的主题的实施方案将变得显而易见,该具体实施方式将结合附图进行阅读。
附图说明
以下附图仅以举例方式而非限制给出,其中当使用相同的附图标记时,其在若干视图中表示对应的元件,并且其中:
图1是用于制造个性化个体单位剂量(IUD)以将规定量的活性物质递送给个体的系统的方框图;
图2是用于制造个性化IUD以将规定量的活性物质递送给个体的方法的流程图;
图3是示出示例性机器的至少部分的方框图,该示例性机器为被配置为执行本文公开的某些方法的计算系统的形式;
图4是处方执行系统的方框图,该处方执行系统用于以电子方式创建处方并通过根据该处方的说明制造个性化IUD来填写该处方;以及
图5是用于以电子方式创建处方并通过根据该处方的说明制造个性化IUD来填写该处方的方法的流程图。
应当理解,附图中的元件是为了简单和清楚而示出的。为了有助于对所示实施方案进行较少妨碍的观察,未必示出在商业上可行的实施方案中可用的常见但易于理解的元件。
具体实施方式
本公开提供了通过使用启用网络的控制系统测量、传送、生产和递送特定于提供给个体的处方的IUD来制造个性化IUD的系统和方法。因此,个体(例如患者)可以与医疗专业人员进行远程通信并使用医疗设备来测量由医师指示的生物特征,该各种生物特征用于允许医疗专业人员诊断病症、治疗、方案和/或医疗处方。然后将医疗处方传送给制造工厂,在该制造工厂中根据每IUD的处方活性物质、剂型和剂量量来制造特定剂型和剂量量(即IUD)。
因此,在本公开的一个方面中,提供了一种直接从制造商生产个性化IUD的方法,这意味着向制造商提供患者处方信息并通过根据该处方的说明制造IUD来执行该处方。IUD是针对该个体个性化并按订单制造的。因此,然后可以将制造商IUD运送给药房、医疗专业人员、分销商或直接运送给患者。医疗专业人员、IUD制造商和个体患者之间的通信可提供用于修改处方并因此修改IUD的制造,以及对现有处方和IUD制造进行更新。
本文公开的制造个性化IUD的系统和方法解决了上述领域中的问题。根据本公开,可以将个性化IUD从制造商(或制造商的分销商)直接发送给患者,从而提高效率和成本以及享有其他益处。
此外,本公开允许跟踪患者处方执行历史,由此制造商可以经由启用网络的控制系统直接与患者和/或医疗专业人员进行通信以进行继续治疗,该继续治疗为相同或改进的治疗。
图1示出了用于制造个性化个体单位剂量(IUD)以将规定量的活性物质递送给个体12的系统10的方框图。根据本发明的系统10通常包括由IUD制造商26操作用于制造个性化IUD的装置13;启用网络的控制系统18,该启用网络的控制系统被配置为以电子方式传送从个体12测量的健康信息;以及任选地生物特征测量模块14、16,该生物特征测量模块与个体12对接。
使用可穿戴的生物特征测量模块14和/或非可穿戴的生物特征测量模块16从个体12测量、获得和/或收集生物特征信息。或者,可以由个体12将生物特征信息直接输入到电脑中,或者医疗专业人员20可以通过网络可视地接收生物特征信息,例如,医疗专业人员20可以经由启用网络的控制系统18观察患者。由此将生物信息提供给启用网络的控制系统18以进行处理和分发。然后将经处理的生物特征信息提供给医疗专业人员20。医疗专业人员20任选地有权访问患者数据库22和/或医疗信息数据库24。启用网络的控制系统18有权访问患者数据库22,以便可以在生物特征信息处理期间利用特定于患者的信息。关于启用网络的控制系统18的其他细节在图3中示出,该图提供了启用网络的控制系统18的一个实施方案的方框图。
一旦收集并处理了个体12的生物特征信息,医疗专业人员20就可以基于从启用网络的控制系统18、患者数据库22和/或医疗信息数据库24获得的信息以及经处理的生物特征信息,向IUD制造商26提供处方。使用启用网络的控制系统18,IUD制造商26使用从医疗专业人员20获得的处方来制造IUD,该IUD可为任何形式,该形式的非限制性示例包括膜剂28、片剂30、胶囊剂32、注射剂34、贴剂36和/或其他剂型38。然后将膜剂28、片剂30、胶囊剂32、注射剂34、贴剂36和/或其他剂型38提供给用户12,理想地以适当的包装并且理想地适当地标记活性物质名称(例如,药品名称)以及剂量(即,IUD中存在的药品的量,通常称为“标记量”)和使用说明(例如,多久服用一次剂量、饭前还是饭后服用、要采取的预防措施或其他重要/有用的使用说明)。
对于IUD的包装和递送,IUD制造商26可以为个体12单独包装每个制造的IUD,或者可以将基于特定于个体12的一个或多个处方制造的多个IUD进行共包装(包装在一起)。共包装方法可以合并给定时间段内为个体12开出的所有药物,由此为该个体12提供简单且方便的递送和依从性选项,该个体可能被要求以不同的时间间隔(例如,早上、晚上、每天、每周、每两周、每两月,以及它们的组合)服用一种或多种药物。共包装可包括针对每天或针对指定剂量方案的具有IUD的单独包装单位,所述IUD可为多于一种类型的药品。例如,可要求患者12同时但以不同频率服用两种药物,即每天服用一种药物并每周服用另一种药物。为了帮助个体12正确地遵循用药说明并适当地依从处方方案,每个制造的IUD可以在其包装上包含标记(诸如颜色代码),该标记包含用药说明。例如,每天的IUD小袋可为红色的,而每周的IUD小袋可为蓝色的。
或者,可以实施可扫描代码技术(诸如QR代码),以针对每个包装的IUD或针对每个IUD本身(即,将代码印刷或压印在IUD本身上)提供适当的药物信息和说明。QR代码可存储与个体12、制造的IUD以及用药说明有关的任何加密或未加密的信息或数据,诸如个体的名字、IUD制造商、药品名称、标记的用量、药物频率(例如,每天一次、每天两次、每周一次等)、服用时间信息(例如,饭前或饭后)、剂量等。此QR代码(未示出)可在递送之前印刷在制造的IUD的每个小袋上或IUD本身上并且可以由个体12的移动设备15扫描以指示该移动设备15容易且方便地将存储在该QR代码中的信息显示到移动设备15。移动设备15安装有能够扫描和识别QR代码的二维条形码的应用程序。该QR代码允许个体12重复检索该IUD的药物信息和使用说明,只要该QR代码未被损坏即可。
图2示出了用于制造个性化IUD以将规定量的活性物质递送给个体12的方法的流程图。在步骤41中确定是否制作了有效处方。如果不存在有效处方,则在步骤42中从个体获得生物特征测量数据,并在步骤44中使用例如可穿戴和/或非可穿戴的生物特征测量模块14、16和/或启用网络的控制系统18将该生物特征测量数据传输给医疗专业人员20。生物特征测量数据可替代地由个体12输入和/或由医疗专业人员20观察的。可由医疗专业人员20在步骤46中基于生物特征信息并且任选地基于从患者数据库22和/或医疗信息数据库24获得的信息来准备处方。然后,在步骤47中,个体12的保险会员资格和承保范围(例如,共付额、免赔额等)可以由保险提供商17验证和确定。除了验证个体12的保险会员资格/状态之外,步骤47还允许一旦医疗专业人员20准备好处方,保险提供商17就可以处理账单和/或索赔。然后可以在步骤48中将处方传输,理想地电子传输给IUD制造商26。在步骤50中经由IUD制造装置13基于处方中的活性物质和剂量方案制造IUD,并在步骤52中将其以膜剂28、片剂30、胶囊剂32、可注射形式34、贴剂36和/或其他剂量形式38递送给个体。如果确实存在如步骤41中所确定的有效处方,则过程继续进行到步骤48。在步骤52之后,过程返回至步骤41以再次确定是否存在有效处方。
在本发明的另一个实施方案中,图4示出了处方执行系统11,该处方执行系统能够收集、分析和处理信息和数据以帮助以电子方式创建处方并通过根据该处方的说明制造个性化IUD来填写该处方。
下文参照根据本发明的实施方案的方法、装置(系统)和电脑程序产品的流程图图解和/或方框图描述该实施方案。应理解的是,流程图图解和/或方框图的每一个方框以及流程图图解和/或方框图中的方框的组合可以通过电脑程序指令来实施。
将此类电脑程序指令提供给“服务器”、“设备”、“计算设备”、“通用电脑”、“电脑设备”、“系统”或“专用计算设备”使机器产生可执行程序,使得当它们被执行时,它们创建用于实施流程图和/或方框图的一个或多个方框中指定的功能/动作的手段。这些电脑程序指令也可存储在电脑可读介质中,该电脑可读介质可指导计算设备或其他可编程数据处理装置以特定方式运行,使得存储在该电脑可读介质中的指令产生制品,该制品包括实施流程图和/或方框图的一个或多个方框中规定的功能/动作的指令手段。
本发明的实施方案既不必限于处理器的任何特定数量、类型或配置,也不必限于任何特定编程语言、记忆存储格式或记忆存储介质。
如本文所用,“参与者”是指患者12、医疗专业人员20、保险提供商17或IUD制造商26。“患者”通常是指处方接受者;“医疗专业人员”通常是指被授权向多个患者开具处方的主治医师或其他医疗专业人员;“保险提供商”通常是指保险福利计划提供商;并且“IUD制造商”通常是指处方药制造商/提供商。
处方执行系统11被设计和配置为使得参与书写处方、授权承保范围和制造根据本发明的个性化IUD的过程的每个参与者(患者12、医疗专业人员20、保险提供商17和IUD制造商26)可以访问并利用处方执行系统11来执行必要任务,以完成以电子方式创建处方并通过根据处方的说明制造个性化IUD来填写该处方的过程。
处方执行系统11利用从患者12获得和收集的生物特征测量信息数据和存储在医疗信息数据库24中的各种与医学和健康有关的信息两者来允许医疗专业人员20以电子方式制定和处理处方,从而允许IUD制造商26基于处方的说明精确地生产个性化IUD。
处方执行系统11为患者12提供了若干益处。更具体地,处方执行系统11通过提供患者药物的综合列表、患者处方的综合列表、与每种药物有关的信息、与每种处方有关的信息、用药说明、制造的IUD的递送状态等为患者12提供查看和管理患者的处方和药物的简便方式。处方执行系统11还提供根据处方专门为个体患者制作和定制(个性化)并递送给患者12的IUD。除了在本公开中描述的过程和系统11的时间和便利性方面之外,还可以制造个性化IUD以确保更高水平的患者安全性,因为所述个性化IUD是考虑到患者病史制作的。
处方执行系统11也向医疗专业人员20提供益处。更具体地,处方执行系统11通过利用在启用网络的控制系统18中配置的多个模块和存储在多个数据库中的综合信息,为医疗专业人员20提供简便的方式来制定和开具处方。另外,处方执行系统11充当中央资料库,所有电子处方被保存和存储在该中央资料库中,使得医疗专业人员20可以容易地检索多个处方或任何特定处方。下文将更详细地讨论多个模块中的每个模块和多个数据库中的每个数据库。
再次参考图4,处方执行系统11通常包括启用网络的控制系统18;数据库管理系统19,该数据库管理系统可操作地链接至该启用网络的控制系统18;前端应用程序21;以及任选的生物特征测量模块14、16,该生物特征测量模块与患者12对接并且可操作地链接至该启用网络的控制系统18。数据库管理系统19被配置为管理多个数据库,该多个数据库包括但不限于用户账户数据库23、患者数据库22、医疗信息数据库24、处方数据库25、保险信息数据库27和提醒通知数据库29。尽管在图4所示的实施方案中示出了一个数据库管理系统19,但是处方执行系统11可以被设计和配置为包括多于一个数据库管理系统。因此,可替代地,多个数据库22、23、24、25、27、29中的每个数据库可以由单独的数据库管理系统19分开管理。
如图3和图4所示,启用网络的控制系统18包括一个或多个处理设备104或计算处理单元(CPU)104。该一个或多个CPU 104可包括专用电路,该专用电路包括执行集成在其中的规定操作的操作能力,例如为专用集成电路(ASIC)和/或微处理器。该一个或多个CPU104被配置为与数据库管理系统19中的多个数据库22、23、24、25、27、29对接。CPU 104可操作以对存储在数据库管理系统19中的程序或指令集起作用。在数据库管理系统19中配置的程序或指令集的执行使CPU 104中的一个CPU执行任务,诸如定位数据、检索数据、处理数据等。此外,该一个或多个CPU 104可执行在启用网络的控制系统18中配置的多个模块(生物特征测量处理模块31、处方处理模块33、保险处理模块35和提醒通知处理模块37)。可执行多个模块31、33、35、37,以收集、分析和处理信息来帮助创建处方并通过根据处方的说明制造IUD来填写该处方。
用户账户数据库23可被配置为存储与处方执行系统11的参与者12、17、20、26相关联的信息。如上所述,处方执行系统11的参与者是参与开具处方和填写处方的所有各方,诸如患者12、医疗专业人员20、保险提供商17和IUD制造商26。存储在用户帐户数据库23中的此类信息的非限制性示例为姓名、地址、联系电话号码、联系电子邮件地址和参与者类型。参与者类型是用于确定参与者可被允许访问处方执行系统11的哪些部分的属性(指示符)。例如,如果参与者类型为患者,则患者可查看和跟踪处方,但是将被限制不能创建处方。用户账户信息可以由每个参与者经由前端应用程序21提供。
患者数据库22被配置为存储与患者12相关联的信息。此类信息的非限制性示例是患者的人口统计特征概况、生物特征测量信息、患者的病史和家族病史。患者的人口统计特征概况包括与患者12相关的所有信息,诸如姓名、年龄、性别、地址、电话号码、电子邮件地址等。病史包括患者12的所有相关病史,诸如治疗医学专业信息、当前处方、过敏症、过去和当前的医疗状况、家族病史等。患者数据库22中存储的信息可以由患者12和/或治疗医疗专业人员20经由前端应用程序21提供。
保险信息数据库27被配置为存储与保险提供商17和患者12的保险福利计划相关联的信息。此类信息的非限制性示例为优先保险(primary insurance)提供商名称、优先保险提供商地址、优先保险计划、优先保险组别编号、优先保险共付额信息、优先保险免赔额信息、优先保险联系电话号码、优先保险联系电子邮件、二级保险提供商名称、二级保险提供商地址、二级保险计划、二级保险组别编号、二级保险共付额信息、二级保险免赔额信息、优先保险联系电话和优先保险联系电子邮件。保险信息可以由保险提供商17和/或患者12经由前端应用程序21提供。
医疗信息数据库24被配置为存储医疗专业人员20制定诊断、治疗和/或处方的必要信息。存储在医疗信息数据库24中的信息的非限制性示例为各种疾病的疾病信息、症状信息和治疗信息。
处方数据库25被配置为存储由医疗专业人员20提供的处方信息和经由处方执行系统11生成的电子处方。存储在处方数据库25中的信息的非限制性示例为药品名称、剂量、用量、重新填写授权、重新填写可用性和患者信息。
提醒通知数据库29被配置为存储与可由处方执行系统11生成并被发送给各种参与者12、17、20、26的各种提醒通知相关联的细节。存储在提醒通知数据库27中的信息的非限制性示例为提醒发送日期、发送者姓名、接受者姓名、提醒消息和用户类型。
多个数据库22、23、24、25、27、29可被配置为具有任何数据库类型,诸如关系数据库、分布式数据库、对象数据库、对象关系数据库、NoSQL数据库等。此外,可以组合数据库22、23、24、25、27、29中的两个或更多个数据库。
数据库管理系统19可为被配置为管理多个数据库22、23、24、25、27、29的任何电子非暂时性形式。数据库管理系统19可驻留在与CPU 104相同或不同的计算设备上。数据库管理系统19可包括MySQL、MariaDB、PostgreSQL、SQLite、Microsoft SQL Server、Oracle、SAPHANA、dBASE、FoxPro、IBM DB2、LibreOffice Base、FileMaker Pro、Microsoft Access和InterSystems Caché。数据库管理系统19的全部或一部分可由第三方维护和/或被配置为云存储设备。
如上所述,处方执行系统11还包括前端应用程序21。前端应用程序21可安装在参与者的计算设备39上,以用于查看和管理数据/信息并在处方执行系统11的参与者12、17、20、26之间进行通信。因此,前端应用程序19可被配置为提供用于输出信息给参与者12、17、20、26。更具体地,前端应用程序21具有图形用户界面(GUI),该GUI被配置为在显示设备上显示;印刷机就绪输出;显示就绪输出;和/或听觉输出。前端应用程序21可以通过网络(诸如全球电脑网络43(例如,互联网))可操作地链接至启用网络的控制系统18。
前端应用程序21可被实现为基于网络的平台(在线/互联网网络应用程序)和基于移动的平台(移动应用程序)两者上的独立应用程序,使得参与者12、17、20、26可使用计算设备39经由互联网访问该独立应用程序,该计算设备包括显示器和在该显示器中实现的输入设备。计算设备的非限制性示例包括个人电脑(膝上型电脑或台式电脑)、移动电话(智能电话)、平板电脑、个人数字助理(PDA),或其他类似设备。电脑设备通常将通过互联网服务提供商(ISP)直接地或通过另一网络接口间接地访问处方执行系统11。
如上所述,处方执行系统11的参与者12、17、20、26为患者12、医疗专业人员20、保险提供商17和IUD制造商26。处方执行系统11被设计和配置为当参与者使用建立的认证证书(例如,用户名和密码)登录到处方执行系统11中时确定用户类型。一旦使用成功登录确定了用户类型,根据本发明实施方案的处方执行系统11就显示与特定参与者类型有关的信息/数据,并提供用于执行任务的必要特征。例如,所有参与者12、17、20、26可查看与患者12相关联的处方,但是处方可仅由医疗专业人员20经由处方执行系统11来处理和创建。
参照图5,在流程图中描述了用于以电子方式创建处方并通过根据处方的说明制造IUD来填写处方的过程。该过程包括以下步骤:基于医疗专业人员20提供的信息以电子方式创建处方;确定是否继续填写该处方;验证患者的保险计划并基于该患者的保险计划确定该处方中开出的药物的承保范围;由IUD制造商26基于该处方制造IUD;以及将制造的IUD递送给患者12。所有这些步骤将使用根据本发明的处方执行系统11来执行。下面将更详细地描述这些步骤。
医疗专业人员20可利用处方执行系统11来为多个患者制定、管理和跟踪处方,并与处方执行系统11的其他参与者进行数据和信息(例如,处方)通信。例如,一旦医疗专业人员20经由前端应用程序21认证并登录到处方执行系统11中,医疗专业人员20就可访问处方生成页面49以管理(查看、更新和/或删除)存储在处方执行系统11中的任何先前创建的处方。
另外,在步骤56中,医疗专业人员20可经由处方生成页面49针对患者12以电子方式开药并以电子方式创建处方。然而,在开药之前,医疗专业人员20可能需要查看存储在多个数据库22、23、24、25、27、29中的与患者12相关的信息。为了方便地提供和检索与患者12相关联的信息,在处方生成页面49上提供患者搜索特征以供医疗专业人员20在以电子方式开药之前启动患者搜索以检索与患者12有关的所有信息。患者特定信息的非限制性示例为患者的人口统计信息(例如,姓名、年龄、性别、出生日期、地址等);病史,包括当前医疗状况(例如,现有症状、过敏症和疾病);从患者12收集并由生物特征测量处理模块31处理的综合生物特征测量信息,包括DNA信息;处方历史;以及家族病史。
一旦完成患者搜索,就还可提供药品的可选列表以及患者特定信息。根据患者的当前的医疗状况、从患者12获得和收集的生物特征测量信息以及医疗信息数据库24中与该生物特征测量信息有关的信息来检索药品列表中所包括的药品,由于这些信息所述药品可有效治疗患者12。然后,医疗专业人员20可浏览药品列表并选择/取消选择可对治疗患者12最有效的一种或多种药物。
处方生成页面49还提供输入栏和/或下拉列表以供医疗专业人员20手动输入和/或选择IUD制造商26填写处方所必要的任何信息(诸如每种选定药品的剂量率和用量)、重填写授权、重填写可用性等。此外,医疗专业人员20可手动输入患者12的用药说明(例如,剂量、频率、餐前/餐后说明等),该用药说明可经由移动设备15检索以如以上结合用于制作个性化IUD的系统10所述在服用药物之前引导患者12。
或者,如果医疗专业人员20认为药品列表不包括治疗患者12的最有效药品,则医疗专业人员20可以通过在处方生成页面49上手动键入药品名称或一些其他药品标识符来提供一种或多种药品。
可以取决于由医疗专业人员20选择/输入的药品是原厂药(brand name drug)还是仿制药(generic drug)来确定和分配IUD制造商。如果确定选择/输入的药品是原厂药,则可经由处方处理模块33自动分配选择/输入的原厂药的制造商,以基于处方的说明制作个性化IUD。相反,如果确定选择/输入的药品是仿制药,则医疗专业人员20可以分配最适合生产选择/输入的仿制药的IUD制造商。
一旦医疗专业人员20已经选择并输入电子生成处方所必要的所有信息并且在经由前端应用程序21将该信息提交给处方执行系统11之前,处方执行系统11可验证由医疗专业人员20提供的处方信息。具体地,利用处方处理模块33来确定医疗专业人员20是否已经提供了所有必需的处方信息,以及医疗专业人员20是否已经正确选择并输入了所有处方信息。
如果由医疗专业人员20提供的所有处方信息都不含错误并且由处方处理模块33进行了验证,则将该信息传输并处理以存储在数据库管理系统19中的处方数据库25中。然后,可以经由启用网络的控制系统18的处方处理模块33以电子方式生成处方,并且可在请求时经由前端应用程序21显示该处方。
在步骤58中,一旦处方执行系统11以电子方式创建了新处方,新处方提醒通知就可自动生成并经由启用网络的控制系统18的提醒通知模块37传输给患者12。新处方提醒通知告知患者12新处方已创建并且准备好由患者12检查。
患者12可经由前端应用程序21登录到处方执行系统11中以访问患者页面51,来方便地查看和跟踪所有的患者处方和药物。具体地,患者页面51显示患者处方的综合可选列表,包括新的或未执行的处方;患者药物的综合可选列表;以及患者12的所有制造的个性化IUD的递送状态。患者页面51可包括搜索特征,该搜索特征允许患者12通过药物属性(诸如当前药物、过去药物、IUD制造商、特定药物等)来搜索药物列表。一旦患者12缩小了药物列表,患者12就可浏览并选择特定药物以检索由医疗专业人员20提供的药物信息和用药说明。这是上文结合用于制作个性化个体单位剂量(IUD)的系统10描述的QR代码方法的替代方法,用于供患者12在服用个性化IUD之前查看用药说明。
患者页面51还可用来搜索患者处方列表,以通过处方属性(诸如未执行的处方、已执行的处方、由医疗专业人员20开具的处方、特定处方等)来显示处方。因此,为了让患者12查看所提醒的新处方,患者12可搜索处方列表以仅显示未执行的处方。
患者页面51还可包括页面51上显示的每个处方的状态指示符,该状态指示符允许患者12更新每个处方的状态。例如,取决于患者12在患者页面51上的动作,处方的状态可被更新为“开始查看”、“继续填写”或“不填写”。
在步骤60中,患者12可经由前端应用程序21查看所提醒的新处方并决定是否继续填写所提醒的新处方。如果患者12决定不继续进行处方,则在步骤62中,可自动生成不填写处方提醒通知并将其经由提醒通知模块37传输给医疗专业人员20,从而通知患者12已经决定不继续填写所提醒的新处方。
如果患者12决定继续填写所提醒的新处方,则在步骤64中,可以自动生成IUD制造过程提醒通知,并且经由提醒通知模块37将其传输给IUD制造商26,以基于所提醒的新处方开始个性化IUD的生产。
同时,在步骤66中,处方执行系统11可基于在数据库管理系统19的保险信息数据库27中存储的信息,经由保险处理模块35确定患者12是否参加了保险提供商17提供的保险福利计划。
如果保险处理模块35确定患者12未参加保险福利计划,则在步骤68中,可以自动生成无保险提醒通知,并将其经由提醒通知模块37进行传输以通知IUD制造商26患者12没有保险计划。而且,无保险提醒通知可指导IUD制造商26处理发票并将该发票直接发送给患者12。
当保险处理模块35确定患者12参加了保险福利计划时,在步骤70中,可自动生成保险提醒通知并将该保险提醒通知经由提醒通知模块37传输以指示保险提供商17启动验证该保险计划并基于该患者的保险计划确定所提醒的新处方中规定的药物的承保范围的过程。
使用患者页面51,患者12还可容易地管理需要重填写的现有处方。如上所述,当患者12选择处方时,包括重填写授权和重填写有效性在内的处方细节被检索并显示在患者页面51上。因此,如果所选择的处方被授权重填写并且重填写是可用的,则患者12可简单地将重填写提醒通知经由提醒通知模块37传输给IUD制造商26,以基于处方的说明创建个性化IUD。然而,如果处方既未被授权重填写,重填写也不可用,则患者12可经由提醒通知模块37将重填写请求提醒通知传输给医疗专业人员20以请求新处方。在这种情况下,医疗专业人员20可简单地经由处方执行系统11处理新处方,或者可在处理新处方之前要求患者经由可穿戴和/或非可穿戴的生物特征测量模块14、16传输当前的生物特征测量信息和/或请求患者访问医疗专业人员的办公室以评估患者的当前医疗状况。
保险提供商17可经由前端应用程序21登录到处方执行系统11中,并访问患者处方页面53以查看和跟踪针对参加由保险提供商17提供的保险福利计划的患者的所有处方。
具体地,患者处方页面53可显示患者处方的综合可选列表,包括新的或未执行的处方。与患者页面51相似,患者处方页面53包括搜索特征,该搜索特征允许保险提供商17缩小列表并通过处方属性(诸如新处方、已执行的处方、由医疗专业人员20所开具的处方、针对患者12的处方、特定处方等)显示处方。因此,为了使保险提供商17确定在患者12的所提醒的新处方中规定的药物的承保范围,保险提供商17可过滤处方列表以仅包括新处方。
当保险提供商17从经过滤的列表中选择新处方中的一个新处方时,显示出了与所选处方有关的患者特定信息、保险信息和处方信息。患者特定信息、保险信息和处方信息的非限制性示例是患者的姓名、地址、保险提供商名称、保险计划、药品名称和重填写授权。
然后,在步骤72中,保险提供商17可将药物费用与患者的保险福利计划和承保范围的条款进行比较,并经由保险处理模块35准备初步金额报告,该初步金额报告包括患者所欠金额((例如,免赔额和共付额,如果适用的话)以及保险提供商17承担财务责任的金额。然后在步骤74中生成保险承保范围提醒通知,并将该保险承保范围提醒通知经由启用网络的控制系统18的提醒通知模块37传输给患者12,从而通知初步金额报告被保存并存储在处方执行系统11中供患者12经由前端应用程序21查看。
患者处方页面53还可包括页面53上显示的每个处方的状态指示符,该状态指示符允许保险提供商17更新处方的状态。例如,取决于保险提供商17在患者处方页面53上的活动,处方的状态可被更新为“已启动保险承保范围分析”、“已完成保险承保范围分析”、“已启动初步金额报告”或“已启动初步金额报告”。
IUD制造商26还可经由前端应用程序21登录到处方执行系统11中,并访问处方执行页面55以查看和管理(更新)分配给IUD制造商26的所有处方。具体地,处方执行页面55显示所有分配的处方的综合可选列表,包括存储在处方执行系统11中的新处方或未执行的处方。与患者页面51和患者处方页面53相似,处方执行页面包括搜索特征,该搜索特征允许IUD制造商26通过处方属性(诸如已执行的处方,未执行的处方、由医疗专业人员20所开具的处方、针对患者12的处方等)缩小列表,因此,为了制造个性化IUD并填写所提醒的新处方,IUD制造商26可过滤所分配处方的列表以仅显示未执行的处方。
当IUD制造商26从经过滤的列表中选择所提醒的新处方时,显示出与所选择的处方有关的患者特定信息和处方信息,以使IUD制造商26可能够根据所提醒的新处方的说明制造IUD。患者特定信息和处方信息的非限制性示例是患者的姓名、地址、过敏症、药品名称、剂量和量,以及由医疗专业人员20提供的用药说明。
在IUD制造商26通过制造个性化IUD填写所提醒的新处方之后,在步骤76中,IUD制造商26继续包装所制造的个性化IUD,并验证每个制造过程已被正确地遵守和执行,然后将经包装的所制造的个性化IUD直接运送给患者12。
在步骤78中,可以自动生成递送提醒通知,并将该递送提醒通知经由提醒通知模块37传输给患者12、医疗专业人员20和保险提供商26,以通知个性化IUD的运送和预期到达日期。
对于包装和递送,处方执行系统11可实现与上文结合用于制作个性化IUD的系统10所描述的相同的特征和方法。
处方执行页面55还可包括页面55上显示的每个处方的状态指示器,该状态指示器允许IDU制造商17更新处方的状态。例如,取决于处方执行页面55上的活动,处方的状态可更新为“已开始生产”、“已完成生产”、“已开始包装”,“已完成包装”和“已运送IUD”。
生物特征测量和设备
用于创建一个或多个个性化个体单位剂量(IUD)的系统10和处方执行系统11可使用多种测量工具为医疗专业人员提供必要信息来制定诊断、治疗、方案和处方中的一者或多者。启用网络的控制系统18使用生物特征测量仪器根据来自医疗专业人员的指示进行测量,并将这些测量结果经由控制网络传送给医疗专业人员。例如,在本公开的一个方面中,个体例如使用直播视频会议进行远程通信,以允许医疗专业人员评估个体的当前状况并执行虚拟检查。医疗专业人员可以与办公室内检查(in-office exam)类似的方式进行检查,询问医疗诊断所需的适当问题,并可以指示患者使用可用的设备进行某些测量,诸如利用他或她自己的生物特征模块。医疗专业人员可请求经由电脑设备输入和发送的测量结果,通过医疗专业人员直接观察传送的测量结果、或者由患者向医疗专业人员口头传达的测量结果。不管从患者接收医学数据的手段如何,医疗专业人员都能够确定诊断或至少做出足以推荐治疗过程、方案和/或开出IUD的适当处方中的一者或多者的医学发现。
美国疾病控制与预防中心(US Centers for Disease Control and Prevention)将生物特征筛查定义为身体特征(诸如身高、体重、BMI、血压、血胆固醇、血糖和有氧适能)的测量,该测量可在医疗专业人员的办公室或医院外(例如在家里或工作场所)进行,并且可用作独立评定或健康评定的一部分。在本发明的个性化系统中使用生物测量学是为了允许简化个体患者的医学评定过程,并快速、有效和具有成本效益地将开具的IUD生产和直接递送给有需要的那些人。此类效率进一步用于降低患者至患者基础上的医疗保健总成本,使库存最小化,并由此使贮藏期限最小化。
启用网络的控制系统理想地包括处理器、记忆存储器和可执行指令,如图3进一步所示。任选地,该系统包括显示设备、字母数字输入设备、光标控制设备、驱动单元、机器可读介质设备和信号生成设备中的一者或多者。尽管也考虑了手动输入使用生物特征测量设备收集和/或测量的测量数据,但是生物特征测量设备理想地但非必须地与处理器对接以促进生物特征测量结果的传输。被设计为提供用于输入对医疗专业人员有用的数据和信息的模板的软件程序和表单也可被包括作为系统的一部分。
该生物特征测量模块可包括侵入式设备和/或非侵入式测量设备,或它们的组合。生物测量模块可包括选自由以下组成的组的设备:声学仪器、视觉仪器、触觉仪器、化学仪器、生物仪器、电气仪器、热仪器和它们的组合。生物特征测量模块可包括选自由以下组成的组的设备:摄像机、视频示波器、照明系统、比色计、肺活量计、霍尔特氏动态心电监测仪、生命体征监测仪、信号监测仪、传感器、超声波探头、测量来自身体的电信号的机器、血液化学仪器、血流测量设备、血液含量测量设备、热测量设备和它们的组合。该生物特征测量模块可包括选自由以下组成的组的设备:脑电图(EEG)机器;心电图(EKG)机器;肌电图(EMG)机器;超声心动图(ECG)机器;心房纤颤设备;听诊器;咽镜;鼻窦镜;耳镜;腹腔镜;皮肤镜;血气测量设备;多用途摄像机;视网膜摄像机;眼睛测量设备;口内摄像机;腹部超声波设备;血管超声波设备;经阴道超声波设备;测量温度、血流量、血糖、肤色、肌理、血脂含量、血液胆固醇含量中的一者或多者的皮肤表面测量设备;加速度计;运动传感器,和它们的组合。
生物特征测量仪器的示例包括但不限于声学仪器、视觉仪器、触觉仪器、化学仪器、生物仪器、电气仪器,和它们的组合。例如,有用的生物特征仪器包括选自以下的那些:摄像机、视频示波器、照明系统、比色计、肺活量计、霍尔特氏动态心电监测仪、生命体征监测仪、信号监测仪、传感器、超声波探头、测量来自身体的电信号的机器、血液化学仪器、血流测量设备、血液含量测量设备、热测量设备和它们的组合。更具体地,用于测量生物特征的设备可选自以下:脑电图(EEG)机器;心电图(EKG)机器;心率监测仪;肌电图(EMG)机器;超声心动图(ECG)机器;心房纤颤设备;听诊器;咽镜;鼻窦镜;耳镜;腹腔镜;皮肤镜;血气测量设备;多用途摄像机;视网膜摄像机;眼睛测量设备;口内摄像机;腹部超声波设备;血管超声波设备;经阴道超声波设备;测量温度、血流量、血糖、肤色、肌理、血脂含量、血液胆固醇含量中的一者或多者的皮肤表面测量设备;加速度计;运动传感器,和它们的组合。
生物特征测量模块还可包括移动设备,该移动设备包括一个或多个软件应用程序,该一个或多个软件应用程序可用于获得生物特征信息、用于进行诊断的信息、用于医学评估的信息、用于评估所述个体所需的治疗效果和/或治疗变化的信息,或它们的组合。此类移动设备可包括移动电话、平板电脑、膝上型电脑、手表或可穿戴设备。在一些情况下,该设备可为位于个体患者身体上或身体内的植入物。
理想地,医疗专业人员能够经由视频会议直接从测量仪器读取结果,但是可替代地,结果可经由互联网传达给医疗专业人员、口头传达,或者通过记录通过网络发送的结果。虚拟检查理想地以与办公室内检查几乎相同的方式进行,并且理想地导致传达/提供给患者的推荐治疗过程、方案或处方。在生成用于药物的IUD的处方的情况下,将该处方传达,理想地以电子方式传达给IUD制造商,然后根据开具的剂型(例如膜剂、片剂、胶囊剂、溶液剂、乳膏剂、贴剂、糖浆剂等)和开具的剂量制作IUD,该开具的剂量取决于多种因素为例如1mg、2mg、5mg、10mg、20mg、30mg、40mg、50mg、60mg、70mg、80mg、90mg、100mg、150mg、200mg、500mg、1000mg以及介于两者之间或甚至更高的各种量,该多种因素包括但不限于所选的活性物质、患者的医疗状况、患者病史以及所开具的方案或治疗。例如,处方可要求含有10mg的CNS药品的口服膜剂或含有500mg的镇痛药品的片剂的IUD。然后,制造商按订单制作个性化处方并将该个性化处方递送(发送)给开处方所针对的个体。或者,可递送给中介,以进行质量检查,或进一步分发给个体。
制造IUD可由活性物质和剂型的任何执业制造商或药物配制人员执行,或在该执业制造商或药物配制人员的监督下执行。然而,与传统系统不同,在传统系统中由执业药师在药房中基于处方制作配混药物,根据本发明,制造商可基于经由网络系统获得的医疗处方和/或健康信息来制作个性化IUD,然后该个性化IUD可全部通过所公开的系统直接递送给患者。
制造IUD可以包括以下步骤中的一个或多个步骤:将载体基质提供给用于制作个性化IUD的装置中的一个或多个装置;将活性物质提供给所述装置中的一个或多个装置;在所述装置中的一个或多个装置中组合活性物质和载体基质;由载体基质和活性物质形成IUD;以及包装该IUD以分发给个体。本文中可以使用本领域已知的与药物产品一起使用的任何包装。
剂型
在本公开中可以使用任何剂型。例如,有用的非限制性剂型包括口服膜剂(包括速溶膜产品)、糯米纸囊剂、胶囊剂、片剂、混悬剂、溶液剂、软膏剂、贴剂、乳膏剂、凝胶剂、锭剂、安瓿、药瓶、糖浆剂、酊剂、醑剂、糖锭、香膏、搽剂、注射剂,和它们的组合。当前,如各个世界监管机构所要求,剂型中存在的活性物质的量的变化不得超过所需量(标示量)的特定百分比。当基于本文所述的剂型应用于剂量单位时,这实际上要求剂型中的活性物质与标示量(即,所需量)相比具有均匀性。
用于本公开中的这些剂型可通过本领域已知的任何手段制作。在本文中有用的制作胶囊的方法的示例在美国专利号5,795,590和4,738,817中描述,这些美国专利全文并入本文。制作可用于本发明中的片剂的方法的示例在美国专利号5,213,738、美国专利号5,456,920和美国专利号5,437,872中有所描述,每个专利的内容都全文并入本文。制作片剂的有用方法的进一步描述在Herbert A.Lieberman和Leon Lachman编辑的“药物剂量形式:片剂第1卷(Pharmaceutical Dosage Forms:Tablets Volume 1)”,Marcel Dekker,Inc,1980中有所描述,该文献的内容以引用方式完全并入本文。
膜剂
在口服膜剂型的情况下,应避免形成附聚物,因为附聚物倾向于使膜组分以及存在的任何活性物质随机分布。当涉及大剂量时,膜剂尺寸的小变化将导致每膜剂的活性物质的量的大差异。如果此类膜剂要包含低剂量的活性物质,则可能的是膜剂的各部分可基本上不含任何活性物质。由于膜剂通常被切成单位剂量,因此某些剂量可不含活性物质或含有对于推荐治疗而言不足量的活性物质。关于切下的膜剂中的活性成分的量未能达到高精度可为对患者有害的。出于该原因,通过常规方法(诸如Fuchs等人的美国专利号4,136,145(“Fuchs”)中所述的方法)形成剂型。Fuchs将不太可能满足政府或监管机构(诸如美国联邦药物管理局(“FDA”))的与活性物质的百分比有关的严格标准,该活性物质的百分比可在剂型中与活性物质的标示量相比发生变化。
用于本公开的口服膜剂可以通过本领域已知的任何手段来制作。制作口服膜剂的方法的示例(包括在本文中有用的描述活性物质内容物的均匀性、制备适当剂量和优化膜工艺、包装和施用IUD的方法)在美国专利号7,425,292;7,357,891;7,666,337;8,017150;8,603 514;8 765 167;8,906,277;8 900 497;9,855,221;9,931,305;8,393,255(切袋机);8,298,583和8,663,696(四氢脂抑素膜);美国专利申请公开号2012/0107402A1(用于分析和确定可摄取膜剂中剂量大小的方法);美国专利号8,282,954(使用没有基于水的组分,即仅具有有机溶剂的浆液制作膜剂);美国专利号9,095,577(稳定的胺体系);美国专利号9,095,495(用于施用有效剂量的设备);美国专利号8,577,488(优化膜废料);美国专利号8,936,825和9561191(将膜直接形成到包装上);美国专利号8,974,826(纳米颗粒膜递送体系);美国专利号8,790,704和9,474,687(肽纳米颗粒膜);美国专利号9,346,601和9,771,173(减少膜的应力开裂);美国专利号8,241,661和8,617,589(具有可变横截面特性的生物相容性膜)中有所描述,,这些专利均转让给Aquestive,Inc.(以前为MonoSol Rx,LLC),所有这些专利全文并入本文。
含量均匀性
每个IUD必须满足含量均匀性要求,该含量均匀性要求确保每个IUD中都有限定量的活性物质。IUD标示有每个IUD中活性物质的具体所需量。IUD被制造为使得成品IUD含有的活性物质含量将变化不超过所需量的10%。例如,如果IUD中活性物质的所需量(标示量)为100mg,则IUD的活性物质量可从90mg至110mg变化,但理想地不在此范围之外。
个体的健康信息
如本文所讨论的,本发明包括用于测量个体的生物特征信息的设备的使用。该信息可以由医疗专业人员看到或直接传输给医疗专业人员,或者替代地可将其存储在网络化的控制系统中,并在日后由医疗专业人员或患者访问。另外,网络化的系统可被配置为链接至一个或多个第三方信息数据库和/或与该一个或多个第三方信息数据库进行数据传输,该一个或多个第三方信息数据库包含患者信息、与诊断有关的信息、疾病状态、先前的患者历史、疾病的治疗方案或医疗状况以及IUD制造商。
当为每个个体患者制定个性化IUD时,该个性化的系统能够具体考虑各种背景,诸如计算生物学、生物信息学、电脑科学、生物学、药理学、医学和生物医学工程。
处方药监测计划(prescription drug monitoring program,PDMP)是跟踪一个州的管制药物处方的电子数据库。PDMP可向卫生主管部门及时提供有关开处方和患者行为的信息,该信息有助于处方药流行并促进有靶向响应。PDMP是可用于解决处方阿片类药物不当使用和滥用的最有前途的工具之一。PDMP在每个州(密苏里州除外)中运行以从药房收集关于分发给患者的管制处方药的数据。每当为管制药物用药填写处方时,药剂师(和一些配药医师)就会向PDMP报告。如果在床旁检测(point of care)时可用,则来自PDMP的信息可为处方者或药剂师提供有关患者使用处方药的历史的重要信息。提供商更容易能够区分合法需要阿片类药物治疗的患者和可能寻求不当使用所述药物的患者。如果有不当使用或滥用的迹象,则在开处方前审查PDMP数据还提供了进行早期干预的机会。此外,许可证发放和监管委员会(licensing and regulatory boards)可使用PDMP数据来确定处方者的异常开处方模式。
因此,本公开的系统或方法可任选地在确定医疗处方和制作IUD之前采用对PDMP数据的审查。该系统或方法还可包括提供和/或存储与个体的健康史有关的信息(即,数据)的步骤,该信息包括有关安全性、功效、副作用、使用活性物质的频率的个体化信息。因为本文公开的系统已经涉及网络化的系统,所以该附加检查可为操作的无缝且流畅的部分。
膜IUD
在一个实施方案中,个性化IUD为膜剂。该膜剂可为本领域中用于递送药物活性物质的任何已知膜剂。
在一个方面中,该膜是用于药物递送的速溶剂型,由此活性剂是经掩味或控释的包衣颗粒。在膜剂型中,经掩味的药剂理想地均匀分布在整个大膜片中,然后将所述大膜片切成IUD。制作用于本发明的膜卷可分成大小相等的单独单位剂量,所述单独单位剂量具有基本上相等量的每种存在的活性组分。该优点特别有用,因为其允许首先形成大面积膜,然后切成单独单位剂量,而不必担心每个单位是否含有基本上均匀含量的活性药物膜剂型。药物膜剂型直到最近才上市,主要是因为在大面积膜中以及由大面积膜切割的IUD中不能实现药品含量的均匀性。因此,例如,本公开的膜具有作为药物剂量递送体系的特殊适用性,因为膜的每个单独单位剂量将含有适当的预定量的药品,该适当的预定量相对于所需量(即标示量)的变化将不超过10%。
在本发明的另一方面中,提供了通过湿式流延法和热熔挤出法形成本发明的膜的方法。在湿式流延法中,通过将聚合物和极性溶剂组合,将该组合形成为膜,以及以受控方式干燥该膜来形成膜产品。优选地,为了保持非自聚集均匀异质性,首先仅将热施加至膜的底侧来干燥膜。理想地,在初始底部干燥阶段期间,基本上不允许对流流(即,热空气流)穿越膜的顶部,直到膜的粘弹性能使得膜组分被“锁定”在适当位置并且无法移动导致不均匀。在那个阶段,可以采用其他加热方法进行干燥。
可以用极性溶剂形成膜剂,所述极性溶剂可为水、极性有机溶剂或它们的组合。可在干燥步骤之前将活性成分添加到聚合物和水的组合中。可替代地或作为控制膜的干燥的补充,聚合物可经选择以提供粘度,该粘度保持非自聚集均匀异质性。此外,理想地将组合物以使空气至混合物中的掺入最小化的方式混合,并且理想地诸如通过在室温下调节、真空处理等对所述组合物进行脱气以使被捕获的空气在干燥过程之前逸出。这用于消除最终膜产品中的气泡和空隙形成,从而进一步改善均匀性。反向辊涂是一种特别有用的涂覆技术,也可用于形成膜剂。
本发明的另一个实施方案可包括一种速溶膜产品,该速溶膜产品含有至少一种水溶性聚合物,该至少一种水溶性聚合物包括单独或与亲水性纤维素聚合物组合的聚环氧乙烷,其中该膜产品可不含添加的增塑剂。优选地,该速溶膜产品包含至少一种水溶性聚合物,该至少一种水溶性聚合物含有约20重量%至100重量%的聚环氧乙烷、约0重量%至80重量%的羟丙基甲基纤维素和约0重量%至80重量%的羟丙基纤维素;活性组分;甜味剂;至少一种调味品;至少一种着色剂,其中该膜产品任选地不含添加的增塑剂、表面活性剂和多元醇。
在本发明的另一方面中,可以通过热熔挤出工艺来形成采用聚环氧乙烷作为成膜聚合物的膜,由此提供可食用的成膜聚合物,并在制造期间添加活性组分,并且将混合物在没有附加溶剂的情况下在高温下共混以形成均匀的基质,并挤出以形成膜。理想地,该膜剂将通过辊进一步成形至指定厚度,并使其冷却并硬化以形成自支撑膜剂。用于挤出制造的特别期望的成膜聚合物是聚环氧乙烷,其在共混期间被加热至约65℃至约80℃以提供柔软的均匀基质。可用单螺杆挤出装置或其他合适的挤出装置完成挤出。
当与微粒包衣的活性成分一起使用时上述挤出工艺的特别优点是,在制造过程期间不存在附加溶剂减少了在制造期间由于溶解或溶剂效应而使经掩味或控释的包衣活性剂溶解或释放的可能性。
本发明的另一方面提供了含有包衣颗粒的膜,所述包衣颗粒包含活性剂和掩味和/或控释包衣。因此,提供了一种药物递送组合物,该药物递送组合物包含(i)可流动的水溶性成膜基质;和(ii)均匀地放置在成膜基质中的微粒生物效应剂;和(iii)被微粒包被或与微粒紧密结合的掩味剂或控释剂,以提供对生物效应剂的掩味。在一些实施方案中,微粒和掩味剂的组合的粒径为200微米或更小,并且可流动的水溶性成膜基质能够被干燥而不会损失微粒生物效应剂在其中的放置的均匀性。
在一些实施方案中,掩味或控释的包衣颗粒的粒径可为50微米至250微米,并且可流动的水溶性成膜基质能够被干燥而不会损失微粒生物效应剂在其中的放置的均匀性。粒径的重要性在口服可摄取的薄膜中提高了,其中均匀性也特别重要,并且现有技术未能认识到此类至关重要的特征。
理想地,微粒和掩味剂的组合的大小具有150微米或更小,或100微米或更小的粒径。所述可流动的水溶性成膜基质可成形为厚度小于约380微米,例如厚度小于约250微米的干膜。理想地,包衣颗粒被完全包埋在最终膜内。换句话说,本发明的干膜理想地具有光滑的表面,该表面没有暴露的药剂或包衣颗粒,该暴露的药剂或包衣颗粒可赋予活性物质砂性或分布不均。因此,在本发明的一个方面中,提供了一种膜载体,该膜载体含有如本文所定义的活性物质的均匀分布,适当地不含干燥时积聚在膜表面上的颗粒。
理想地,掩味剂或控释剂是包被在生物效应剂的各部分上的薄膜。有用的掩味剂包含聚合物材料。水溶性聚合物也是有用的。理想地,水溶性聚合物的平均分子量等于或大于约40,000。此外,水溶性聚合物可为丙烯酸类聚合物、纤维素聚合物,和它们的组合。另外,乙烯基聚合物、冠醚、氢化油和蜡以及它们的组合也可用作掩味剂。
在本文所述的一些实施方案中,薄膜药品递送组合物包含:(a)可食用的水溶性成膜基质;和(b)均匀放置在该成膜基质中的包衣微粒活性组分,其中该微粒活性组分上的包衣是掩味剂或控释剂,并且其中该包衣微粒活性组分的粒径为50微米至250微米且均匀分布在该膜组合物中。
在一些其他实施方案中,提供了一种薄膜药品递送组合物,该薄膜药品递送组合物包含:(a)可食用的水溶性成膜基质,该可食用的水溶性成膜基质包含至少一种水溶性聚合物,该至少一种水溶性聚合物包含单独或与亲水性纤维素聚合物组合的聚环氧乙烷;和(b)均匀放置在该成膜基质中的包衣微粒活性组分,其中微粒活性组分上的包衣是掩味剂和/或控释剂,并且其中活性组分均匀地分布在膜组合物中。
可用于制造IUD的聚合物
可用于制造IUD的聚合物可以在制造过程期间采用极性溶剂(诸如水或醇类)来软化或溶解聚合材料。优选地,聚合物将是水溶性的。如本文所用,短语“水溶性聚合物”及其变体是指至少部分可溶于水,并且理想地完全或主要可溶于水或吸收水的聚合物。吸收水的聚合物通常被称为水可溶胀的聚合物。可用于本发明的材料可在室温和其他温度(诸如超过室温的温度)下为水溶性或水可溶胀的。而且,该材料可在小于大气压的压力下为水溶性或水可溶胀的。理想地,水溶性聚合物是水溶性的或水可溶胀的,具有至少20重量%的吸水率。吸水率为25重量%或更大的水可溶胀聚合物也是有用的。由此类水溶性聚合物形成的本发明的膜或其他剂型理想地是充分水溶性的,以可在与体液接触时溶解。
可用于掺入本发明的膜或其他剂型中的其他聚合物包括可生物降解的聚合物、共聚物、嵌段聚合物和它们的组合。满足上述标准的一种或多种已知有用聚合物类别有:聚(乙醇酸)(PGA)、聚(乳酸)(PLA)、聚二噁烷、聚草酸酯、聚(α-酯)、聚酸酐、聚乙酸酯、聚己内酯、聚(原酸酯)、聚氨基酸、聚氨基碳酸酯、聚氨酯、聚碳酸酯、聚酰胺、聚(氰基丙烯酸烷基酯),以及它们的混合物和共聚物。附加有用的聚合物包括L-乳酸和D-乳酸的立体聚合物、双(对羧基苯氧基)丙烷酸和癸二酸的共聚物、癸二酸的共聚物、己内酯的共聚物、聚(乳酸)/聚(乙醇酸)/聚乙二醇共聚物、聚氨酯和(聚(乳酸)的共聚物、聚氨酯和(聚乳酸)的共聚物、α-氨基酸的共聚物、α-氨基酸和己酸的共聚物、谷氨酸α-苄酯和聚乙二醇的共聚物、琥珀酸酯和聚(乙二醇)的共聚物、聚磷腈、多羟基链烷酸酯,和它们的混合物。考虑了二元和三元体系。
其他有用的特定聚合物包括以Medisorb和Biodel商标出售的那些。Medisorb材料由美国特拉华州威尔明顿市的杜邦公司(Dupont Company of Wilmington,Del)销售,并且通常被标识为“丙交酯/乙交酯共聚物”,含有“丙酸的2-羟基聚合物和羟基乙酸的羟基聚合物”。四种此类聚合物包括:丙交酯/乙交酯100L,据信是熔点在338℉-347℉(170℃-175℃)范围内的100%丙交酯;丙交酯/乙交酯100L,据信是熔点在437℉-455℉(225℃-235℃)范围内的100%乙交酯;丙交酯/乙交酯85/15,据信为85%的丙交酯和15%的乙交酯,其熔点在338℉-347℉(170℃-175℃.)的范围内;以及丙交酯/乙交酯50/50,据信为50%丙交酯和50%乙交酯的共聚物,其熔点在338℉-347℉.(170℃-175℃.)的范围内。
Biodel材料代表了一系列化学上不同的各种聚酸酐。尽管可使用多种不同的聚合物,但是期望选择聚合物以提供所需的混合物粘度。例如,如果活性物质或其他组分不溶于所选择的溶剂,则需要将提供更高粘度的聚合物来帮助保持均匀性。另一方面,如果组分可溶于溶剂中,则提供较低粘度的聚合物可为优选的。
在上述聚合物中,聚环氧乙烷(PEO)在单独使用或与亲水性纤维素聚合物组合使用时,特别适合于热熔挤出工艺,并且实现了柔韧的强膜。可任选选地包含附加的增塑剂或多元醇。用于与PEO组合的合适的纤维素聚合物的非限制性示例包括HPC和HPMC。PEO和HPC基本上没有胶凝温度,而HPMC的胶凝温度为58-64℃(Methocel EF,可从Dow Chemical Co.商购获得)。此外,这些膜即使在基本不含有机溶剂的情况下也足够柔韧,所述膜可以在不损害膜性能的情况下取下。如此,如果不存在溶剂,则膜剂中不存在增塑剂。当聚合物组分含有合适水平的PEO时,基于PEO的膜还表现出良好的抗撕裂性,很少或没有卷曲,以及快速的溶解速率。
为了实现所需的膜特性,可改变聚合物组分中PEO的水平和/或分子量。改变PEO含量会影响诸如抗撕裂性、溶解速率和粘附倾向的性质。因此,一种控制膜特性的方法是改变PEO含量。例如,在一些实施方案中,快速溶解的膜剂是期望的。通过改变聚合物组分的含量,可以实现所需的溶解特性。
根据本发明,聚合物组分中的PEO理想地在约20重量%至100重量%的范围内。在一些实施方案中,PEO的量理想地在约1mg至约200mg的范围内。
在本发明的一些实施方案中,亲水性纤维素聚合物(诸如HPMC)也可以约0重量%至约80重量%或以与PEO至多约4:1的比率并且理想地约1:1的比率用作水溶性聚合物。
在一些实施方案中,可能期望改变PEO水平以促进某些膜特性。为了获得具有高抗撕裂性和快速溶解速率的膜,聚合物组分中约50%或更高的PEO水平是理想的。为了实现防止粘附,即防止膜粘附到口腔的顶部,PEO水平为约20%至75%是期望的。然而,在一些实施方案中,可能期望粘附到口腔的顶部,诸如对于施用给动物或儿童。在此类情况下,可采用较高水平的PEO。更具体地,取决于预期用途,可控制膜的结构完整性和溶解,使得膜可粘附至粘膜并容易去除,或者可更牢固地粘附并且难以去除。
PEO的分子量也可变化。可能需要高分子量(诸如约400万)的PEO,以增加膜的粘膜粘附性。更理想地,分子量可在约100,000至900,000,更理想地约100,000至600,000,并且最理想地约100,000至300,000的范围内。在一些实施方案中,可能需要在聚合物组分中组合高分子量(600,000至900,000)和低分子量(100,000至300,000)的PEO。
例如,可以通过将少量的高分子量PEO与大量的较低分子量PEO组合来获得某些膜特性,诸如快速溶解速率和高抗撕裂性。理想地,此类组合物在PEO共混聚合物组分中含有约60%或更高水平的较低分子量PEO。
为了平衡防止粘附、快速溶解速率和良好的抗撕裂性的特性,所需的膜组合物可包含约50%至75%的低分子量PEO,任选地与少量的较高分子量的PEO组合,其余为含有亲水性纤维素聚合物(HPC或HPMC)的聚合物组分。
流体基质和组分的粘度
聚合物在影响剂型(诸如混悬剂、液体,溶液剂和膜剂)的粘度方面起着重要作用。粘度是液体的一种控制活性物质在乳液、胶体或混悬剂中的稳定性的特性。通常,基质的粘度将从约400cps至约100,000cps,优选从约800cps至约60,000cps,并且最优选从约1,000cps至约40,000cps变化。当剂型是膜剂时,理想地,成膜基质的粘度将在干燥过程开始时迅速增加,该粘度是确保活性物质的微粒基本上被“锁定”在适当位置并因此基本上均匀地放置在承载它们的基质中的因素。
可取决于基质内的其他组分,基于所选择的活性物质来调节载体基质的粘度。粘度对于本质上是微粒的活性物质特别重要。例如,如果组分不溶于所选择的溶剂内,则可选择适当的粘度以防止组分沉降,沉降将不利地影响所得膜或液体剂型的均匀性。可以不同方式调节粘度。为了增加膜基质的粘度,可选择具有较高分子量的聚合物或可添加交联剂,诸如钙、钠和钾的盐。粘度也可通过调节温度或通过添加粘度增加组分来调节。将增加粘度或稳定乳液/混悬剂的组分包括较高分子量的聚合物、多糖和树胶,所述较高分子量的聚合物、多糖和树胶包括但不限于藻酸盐、角叉菜胶、羟丙基甲基纤维素、刺槐豆胶、瓜尔胶、黄原胶、右旋糖酐、阿拉伯胶、吉兰糖胶,和它们的组合。
还已经观察到,某些在单独使用时通常需要增塑剂才能获得柔韧膜的聚合物,可在不使用增塑剂的情况下进行组合而仍然获得柔韧膜。例如,HPMC和HPC当组合使用时提供了具有对于制造和存储而言适当的可塑性和弹性的柔韧强膜。不需要附加的增塑剂或多元醇来实现柔韧性。
载体基质可为在药物组分配制中使用的任何已知的惰性组分或组分混合物。如本领域普通技术人员容易理解的,取决于剂型和所需的终产品,载体基质差异很大。例如,载体基质可为包含聚合物、溶剂、添加剂和/或润滑剂的制剂。它可包括粉末、液体或它们的组合。
用于挤出膜的聚合物
在本发明的替代性实施方案中,可使用热熔挤出来形成膜。对于挤出过程,聚合物必须是热塑性的,意味着可将聚合物在合适的装置中熔融,根据需要与其他成分共混,然后在压力下通过孔口挤出以提供膜。
活性剂
用于本文的自支撑膜剂的合适活性物质包括但不限于以下治疗类别:血管紧张素转化酶抑制剂;肾上腺素能药;肾上腺皮质类固醇;肾上腺皮质抑制剂;醛固酮拮抗剂;生物碱;氨基酸;合成代谢药;复原剂(analeptic);镇痛剂;麻醉剂;食欲抑制剂;抗痤疮剂;抗肾上腺素药;抗过敏药;抗阿米巴药;抗贫血药;抗心绞痛药;抗焦虑剂;抗关节炎药;抗心律失常药;抗哮喘剂;抗动脉粥样硬化剂;抗胆固醇血症药;抗菌药;抗生素;抗胆碱能药;抗凝血剂;抗惊厥药;抗抑郁药;抗糖尿病药;抗腹泻药;抗利尿剂;解毒剂;止吐药;抗癫痫药;抗纤维蛋白溶解药;抗真菌剂;抗出血药;抗组胺药;抗高血脂药;抗高血压药;抗低血压药;抗感染药(全身性和非全身性);抗炎剂;抗脂质药;抗躁狂药;抗微生物剂;抗偏头痛药;抗有丝分裂剂;抗真菌剂、止恶心药;抗赘瘤药;抗中性白细胞减少药;抗肥胖药;抗寄生虫药;抗帕金森症药;抗增殖剂;抗精神病药;退热药;抗风湿药;抗皮脂溢药;抗分泌药;解痉剂;抗中风药;抗血栓形成药;抗甲状腺药;抗肿瘤药;镇咳药;抗溃疡药;抗尿酸血症药;抗病毒药;食欲抑制剂;食欲刺激剂;生物反应调节剂;血糖调控剂;血液调节剂;血液代谢调节剂;骨吸收抑制剂;支气管扩张剂;心血管药物;中枢神经系统兴奋剂;大脑扩张药物;避孕药;冠状动脉扩张药;胆碱能药;咳嗽遏抑剂;减充血剂;镇静剂;诊断用辅助药;膳食补充剂;利尿剂;多巴胺能药剂;酶;雌激素受体激动剂;子宫内膜异位控制剂;祛痰剂;勃起功能障碍疗法;红细胞生成药;纤溶药(ibrinolytic);生育药;荧光剂;游离氧自由基清除剂;胃酸抑制剂;胃肠蠕动效应剂;遗传修饰药物;糖皮质激素;毛发生长刺激剂;止血药;组胺H2受体拮抗剂;顺式治疗药;激素;高钙血症管理剂;低钙血症管理剂;降胆固醇药;降血糖药;降血脂药;降血压药;离子交换树脂;显像剂;免疫剂;免疫调节剂;免疫调控剂;免疫刺激剂;免疫抑制剂;角质溶解药;缓泻药;LHRH激动剂;情绪调节剂;晕动病制剂;粘液溶解剂;肌肉松弛剂;散瞳药;鼻腔减充血剂;神经肌肉阻断剂;神经保护剂;NMDA拮抗剂;非激素甾醇衍生物;骨质疏松症治疗剂;催产剂;副交感神经阻滞药;拟副交感神经药;纤溶酶原激活剂;血小板活化因子拮抗剂;血小板聚集抑制剂;前列腺素;心理治疗剂;精神药物;放射性药;呼吸剂;杀疥螨药;硬化剂;镇定剂;镇静催眠药;选择性腺苷A1拮抗剂;血清素拮抗剂;血清素抑制剂;血清素受体拮抗剂;戒烟疗法;类固醇;兴奋剂;交感神经阻滞药;子宫松弛剂(terinerelaxant);甲状腺激素;甲状腺抑制剂;拟甲状腺素药;安定剂;震颤疗法;肌萎缩侧索硬化症药;脑缺血剂;佩吉特氏病药剂;不稳定心绞痛药物;血管收缩剂;血管扩张剂;体重控制药;伤口愈合剂;黄嘌呤氧化酶抑制剂;以及它们的组合。
适用于本文的药物活性物质的示例包括抗酸剂、H2拮抗剂和镇痛药。例如,可以使用单独的或与氢氧化镁和/或氢氧化铝组合的成分碳酸钙来制备抗酸剂。此外,抗酸剂可与H2拮抗剂组合使用。
镇痛药包括阿片类和阿片类衍生物,诸如羟考酮(可作为商购获得)、布洛芬(可作为MotrinMotrinAdvilMotrinMotrinMidol CrampMotrin Migraine和商购获得)、阿司匹林(可作为Genuine和商购获得)、对乙酰氨基酚(可作为SilapapSilapapTylenolTylenol ExtraTylenol Infants'TylenolTylenol 和商购获得),以及它们的组合,所述组合可任选地包含咖啡因。其他的疼痛缓解剂也可用于本发明,包括盐酸哌替啶(可作为商购获得)、辣椒素(可作为商购获得),硫酸吗啡和盐酸纳曲酮(可作为商购获得)、盐酸氢吗啡酮(可作为商购获得)、萘磺酸丙氧芬和对乙酰氨基酚(可作为商购获得)、芬太尼(可作为 和商购获得)、透明质酸钠(可作为商购获得)、阿达木单抗(可作为商购获得)、琥珀酸舒马曲普坦(可作为商购获得)、芬太尼离子电渗疗法(可作为商购获得)、柠檬酸邻甲苯海拉明(可作为商购获得)、四水水杨酸镁(可作为商购获得)、盐酸羟氢吗啡酮(可作为Opana商购获得)、美索巴莫(可作为商购获得)、卡立普多(可作为商购获得)、盐酸曲马多(可作为和商购获得)、硫酸吗啡(可作为MS商购获得)、美他沙酮(可作为商购获得)、盐酸羟可待酮(可作为商购获得)、对乙酰氨基酚/盐酸羟可待酮(可作为商购获得)、羟考酮/阿司匹林(可作为商购获得)、酒石酸氢可酮/对乙酰氨基酚(可作为商购获得)、酒石酸氢可酮/布洛芬(可作为商购获得)、奈帕芬胺(可作为商购获得)和普瑞巴林(可作为商购获得)。
本文公开的自支撑膜剂还可包括诸如NSAID的药剂,包括依托度酸(可作为商购获得)、酮咯酸氨丁三醇(可作为或商购获得)、萘普生钠(可作为商购获得)、氟比洛芬(可作为商购获得)、双氯芬酸钠/米索前列醇(可作为商购获得)、塞来昔布(可作为商购获得)、舒林酸(可作为商购获得)、奥沙普秦((可作为商购获得)、吡罗昔康(可作为商购获得)、吲哚美辛(可作为商购获得)、美洛昔康(可作为商购获得)、甲芬那酸(可作为商购获得)、托美汀钠(可作为商购获得)、三水杨酸胆碱镁(可作为商购获得)、双氯芬酸钠(可作为商购获得)、双氯芬酸钾(可作为或商购获得)和米索前列醇(可作为商购获得)、阿片类激动剂和拮抗剂,诸如丁丙诺啡和纳洛酮是用于本发明的药品的其他示例。
用于本文中使用的其他优选活性成分的其他优选药品包括止泻药,诸如洛哌丁胺(可作为ImodiumQCHealth Care AmericaLeader和商购获得)、硝唑尼特(可作为商购获得)、和盐酸地芬诺酯/硫酸阿托品(可作为商购获得);抗组胺药;镇咳药;减充血剂;维生素;和呼吸清新剂;单独或组合用于感冒、疼痛、发烧、咳嗽、充血、流鼻涕和过敏的常见药品,诸如对乙酰氨基酚、布洛芬、马来酸氯苯那敏、右美沙芬、右美沙芬HBr、去氧肾上腺素HCl、伪麻黄碱HCl、苯海拉明和它们的组合,诸如右美沙芬HBr和去氧肾上腺素HCl(可作为获得),可包含在本发明的膜组合物中。
可用于本文的其他活性剂包括但不限于酒精依赖性治疗,诸如阿坎酸钙(可作为商购获得);过敏症治疗药物,诸如盐酸异丙嗪(可作为商购获得)、苯磺酸贝托司汀(可作为商购获得)、氯苯吡醇胺氢可酮/氯苯那敏-磺化二乙烯苯(可作为商购获得)、盐酸西替利嗪(可作为商购获得)、盐酸西替利嗪/盐酸伪麻黄碱(可作为商购获得)、盐酸异丙嗪/磷酸可待因(可作为与可待因一起商购获得)、吡嘧司特(可作为商购获得)、盐酸非索非那定(可作为商购获得)、盐酸美克洛嗪(可作为商购获得)、盐酸氮卓斯汀(可作为商购获得)、尼扎替丁(可作为商购获得)、地氯雷他定(可作为商购获得)、色甘酸钠(可作为商购获得)、盐酸依匹斯汀(可作为商购获得)、盐酸氮卓斯汀(可作为商购获得)、泼尼松龙磷酸钠(可作为Orapred商购获得)、盐酸奥洛他定(可作为商购获得)、富马酸酮替芬(可作为商购获得)、和孟鲁司特钠(可作为商购获得);以及抗组胺药,诸如盐酸苯海拉明(可作为商购获得)、氯雷他定(可作为商购获得)、阿司咪唑(可作为商购获得)、萘丁美酮(可作为商购获得)、盐酸苯海拉明((可作为商购获得)和克立马丁(可作为商购获得)。
用于本公开的活性物质还可包括阿尔茨海默氏症治疗药物,诸如盐酸他克林(可作为商购获得)、加兰他敏(可作为商购获得)、盐酸多奈哌齐(可作为商购获得)、酒石酸卡巴拉汀(可作为商购获得)、辛炔(可作为商购获得)和美金刚(可作为商购获得);贫血药物,诸如氰钴胺(可作为商购获得)和纳米氧化铁(可作为商购获得);麻醉药,诸如安替比林和苯佐卡因(可作为和商购获得);心绞痛药,诸如苯磺酸氨氯地平(可作为商购获得)、硝酸甘油(可作为商购获得)、单硝酸异山梨酯(可作为商购获得)和二硝酸异山梨酯(可作为商购获得);镇痛药,诸如愈创木酚甘油醚;抗阿尔茨海默氏症药物,诸如尼麦角林;和CaH拮抗剂,诸如硝苯地平(可作为和商购获得)。
可用于本公开中的活性物质还可包括抗哮喘药,诸如硫酸沙丁胺醇(可作为商购获得)、异丙托溴铵(可作为商购获得)、昔萘酸沙美特罗(可作为商购获得)、扎鲁司特(可作为商购获得)、氟尼缩松(可作为商购获得)、硫酸奥西那林(可作为商购获得)、沙丁胺醇吸入剂(可作为商购获得)、硫酸特布他林(可作为商购获得)、福莫特罗(可作为商购获得)、色甘酸钠(可作为商购获得)、盐酸左沙丁胺醇(可作为商购获得)、齐留通(可作为商购获得)、丙酸氟替卡松/沙美特罗(可作为商购获得)、硫酸沙丁胺醇/曲安奈德(可作为商购获得)、二甲基黄嘌呤(可作为商购获得)、和倍氯米松(可作为商购获得);血管性水肿药物,诸如C1酯酶抑制剂(人)(可作为商购获得)和艾卡拉肽(可作为商购获得);和抗菌药物,诸如甲氧苄啶/磺胺甲噁唑(可作为商购获得)、莫匹罗星(可作为商购获得)、甲硝唑(可作为商购获得),乙酰磺胺异噁唑(可作为商购获得)、水杨酸亚铋和甲硝唑/盐酸四环素(可作为Helidac商购获得)、呋喃妥因(可作为商购获得)、诺氟沙星(可作为商购获得)、琥乙红霉素/乙酰磺胺异噁唑(可作为商购获得)和左氧氟沙星(可作为商购获得)。
其他活性物质还可包括一种或多种抗生素,包括阿莫西林(可作为商购获得)、氨苄青霉素(可作为和商购获得)、阿莫西林/克拉维酸钾(可作为商购获得)、盐酸莫西沙星(可作为商购获得)、贝西沙星(可作为商购获得)、克拉霉素(可作为商购获得)、头孢布烯(可作为商购获得)、头孢呋辛酯(可作为商购获得)、头孢丙烯(可作为商购获得)、盐酸环丙沙星(可作为和商购获得)、磷酸克林霉素(可作为Cleocin商购获得)、盐酸多西环素(可作为商购获得)、地红霉素(可作为商购获得)、红霉素(可作为作为和商购获得)、局部用红霉素(可作为商购获得)、吉米沙星(可作为商购获得)、氧氟沙星(商业上称为)、泰利霉素(可作为商购获得)、盐酸洛美沙星(可作为商购获得)、盐酸米诺环素(可作为商购获得)、磷霉素氨丁三醇(可作为商购获得),青霉素和钾(可作为Penicillin商购获得)、甲氧苄啶(可作为商购获得)、盐酸环丙沙星(可作为Proquin商购获得)、利福平、异烟肼和吡嗪酰胺(可作为商购获得)、头孢托仑(可作为商购获得)、头孢克肟(可作为商购获得)、四环素(可作为Achromycin和商购获得)、妥布霉素(可作为商购获得)、利福昔明(可作为商购获得)、阿奇霉素(可作为商购获得)、阿奇霉素悬浮液(可作为商购获得)、利奈唑胺(可作为商购获得)、过氧化苯甲酰和克林霉素(可作为商购获得)、红霉素和过氧化苯甲酰(可作为商购获得)、地塞米松(可作为商购获得)、环丙沙星和地塞米松(可作为商购获得)、硫酸多粘菌素B/硫酸新霉素/氢化可的松(可作为商购获得)、硫酸粘菌素/硫酸新霉素/醋酸氢化可的松/溴化十六基啶二胺(可作为Cortisporin-TC商购获得)、头孢氨苄盐酸盐(可作为商购获得)、头孢地尼(可作为商购获得)和加替沙星(可作为商购获得)。
其他有用的活性物质包括癌症治疗药物,包括环磷酰胺(可作为商购获得)、甲氨蝶呤(可作为和商购获得)、枸橼酸它莫西芬(可作为商购获得)、贝伐单抗(可作为商购获得)、依维莫司(可作为商购获得)、帕唑帕尼(可作为商购获得)、和阿那曲唑(可作为商购获得);白血病治疗药,诸如奥法木单抗(可作为商购获得);抗血栓药,例如抗凝血酶重组冻干粉(可作为商购获得)、普拉格雷(可作为商购获得);抗凝血剂,诸如阿司匹林与延迟释放的双嘧达莫(可作为商购获得)、华法林钠(可作为商购获得)、双嘧达莫(可作为商购获得)、达肝素(可作为商购获得)、达那肝素钠(可作为商购获得)、依诺肝素(可作为商购获得)、肝素(可作为Hep-Lock、Hep-Pak、Hep-Pak CVC、Heparin Lock Flush商购获得)、亭扎肝素(可作为商购获得)和硫酸氢氯吡格雷(可作为商购获得);止吐药,诸如盐酸格拉司琼(可作为商购获得)和纳必隆(可作为商购获得)、盐酸曲美苄胺(可作为商购获得)和盐酸昂丹司琼(可作为商购获得);抗真菌治疗药,诸如酮康唑(可作为商购获得)、泊沙康唑(可作为商购获得)、环吡酮(可作为商购获得)、灰黄霉素(可作为商购获得)、硝酸奥昔康唑(可作为商购获得)、氟康唑(可作为商购获得)、硝酸舍他康唑(可作为商购获得)、盐酸特比萘芬(可作为商购获得)、环吡酮(可作为商购获得)、制霉菌素/曲安奈德(可作为商购获得)、硝酸益康唑(可作为商购获得)、伊曲康唑(可作为商购获得)和特康唑(可作为商购获得)。
活性剂还可包括抗炎药,诸如硫酸羟氯喹(可作为商购获得)、丙酸氟替卡松(可作为商购获得)、康纳单抗(可作为商购获得)、安西奈德(可作为商购获得)、甲基强的松龙(可作为商购获得)、布地奈德(可作为Entocort商购获得)、阿那白滞素(可作为商购获得)、醋酸双氟拉松(可作为商购获得)、和依那西普(可作为商购获得);抗痉挛药,诸如苯巴比妥/硫酸莨菪碱/硫酸阿托品/氢溴酸东莨菪碱(可作为商购获得;抗病毒治疗药,诸如磷酸奥司他韦(可作为商购获得);抗寄生虫药物,包括替硝唑(可作为商购获得);食欲治疗药,诸如醋酸甲地孕酮(可作为Megace商购获得)、盐酸芬特明(可作为商购获得)和盐酸安非拉酮(可作为商购获得);关节炎药物,包括来氟米特(可作为商购获得)、赛妥珠单抗(可作为商购获得)、双氯酚酸钠(可作为商购获得)、戈利木单抗(可作为商购获得)、和托珠单抗(可作为商购获得);膀胱控制药物,诸如曲司氯铵(可作为商购获得)、醋酸去氨加压素(可作为商购获得)、酒石酸托特罗定(可作为商购获得)、氯化羟丁宁(可作为或商购获得)、达非那新(可作为商购获得)和琥珀酸索非那新(可作为商购获得);血管收缩剂,诸如马来酸甲基麦角新碱(可作为商购获得品);血浆尿酸管理剂,诸如拉布立酶(可作为商购获得);缺铁性贫血药物,诸如纳米氧化铁(可作为商购获得);淋巴瘤药物,例如普拉曲沙(可作为商购获得)、罗米地辛(可作为商购获得);疟疾药物,诸如蒿甲醚/苯芴醇(可作为商购获得);低钠血症药物,诸如托伐普坦(可作为商购获得);用于治疗血管性血友病的药物(可作为商购获得);抗高血压药,诸如曲前列环素(可作为商购获得)、他达拉非(可作为商购获得);降低胆固醇的药物,包括帕立骨化醇(可作为商购获得)、匹伐他汀(可作为商购获得)、洛伐他汀、烟酸(可作为商购获得)、盐酸考来替泊(可作为商购获得)、瑞舒伐他汀钙(可作为商购获得)、氟伐他汀钠(可作为商购获得购得),阿托伐他汀钙(可作为购得),洛伐他汀(可作为商购获得)、烟酸(可作为商购获得)、普伐他汀钠(可作为商购获得)、具有缓冲阿司匹林的普伐他汀钠(可作为Pravigard商购获得)、消胆胺(可作为商购获得)、辛伐他汀和烟酸(可作为商购获得)、阿替洛尔,氯噻酮(可作为商购获得)、阿替洛尔(可作为商购获得)、非诺贝特(可作为商购获得)、非诺贝特(可作为商购获得)、依泽替米贝/辛伐他汀(可作为商购获得)、考来维仑(可作为商购获得)、富马酸比索洛尔(可作为商购获得)、依泽替米贝(可作为商购获得)、富马酸比索洛尔/氢氯噻嗪(可作为商购获得)、和辛伐他汀(可作为商购获得)。
本文所包括的药物活性物质还可包括慢性肾脏疾病药物,诸如帕立骨化醇(可作为商购获得);避孕药,包括依托孕酮(可作为商购获得)、醋酸炔诺酮、乙炔雌二醇(可作为Loestrin 24商购获得)、乙炔雌二醇、诺孕曲明(可作为Ortho商购获得)、左炔诺孕酮(可作为Plan商购获得)、左炔诺孕酮和乙炔雌二醇(可作为商购获得)、左炔诺孕酮、乙炔雌二醇(可作为商购获得)和醋酸甲羟孕酮(可作为商购获得);COPD药物,诸如酒石酸阿福特罗(可作为商购获得)和异丙托溴铵、硫酸沙丁胺醇(可作为商购获得);咳嗽遏抑剂,包括苯佐那酯(可作为商购获得)、愈创甘油醚、磷酸可待因(可作为Tussi-Organidin商购获得)和对乙酰氨基酚、磷酸可待因(可作为Tylenol和商购获得);用于治疗糖尿病的药物,包括盐酸吡格列酮、盐酸二甲双胍(可作为ACTOplus商购获得)、甲磺酸溴隐亭(可作为商购获得)、利拉鲁肽(可作为商购获得)、沙格列汀(可作为商购获得)、盐酸吡格列酮(可作为商购获得),格列美脲(可作为商购获得)、马来酸罗格列酮、盐酸二甲双胍(可作为商购获得)、马来酸罗格列酮(可作为商购获得)、马来酸罗格列酮(可作为商购获得)、艾塞那肽(可作为商购获得)、艾塞那肽(可作为商购获得)、氯磺丙脲(可作为商购获得)、盐酸吡格列酮、格列美脲(可作为商购获得)、盐酸二甲双胍(可作为商购获得)、格列吡嗪(可作为商购获得)、格列本脲,二甲双胍(可作为和商购获得)、盐酸二甲双胍(可作为商购获得)、西他列汀(可作为商购获得)、地特胰岛素(可作为商购获得)、格列吡嗪、盐酸二甲双胍(可作为商购获得)、格列本脲(可作为商购获得)、瑞格列奈(可作为商购获得)、阿卡波糖(可作为商购获得)、那格列奈(可作为商购获得)、醋酸普兰林肽(可作为商购获得)、卡格列净(可作为商购获得)、利格列汀(可作为商购获得)、达格列净(可作为商购获得)、甘精胰岛素(可作为或商购获得)、门冬胰岛素(可作为商购获得)、赖脯胰岛素、依帕列净(可作为商购获得)和妥拉磺脲(可作为商购获得)。
本发明的其他有用的活性物质可包括消化剂,诸如柳氮磺吡啶(可作为商购获得)、雷贝拉唑钠(可作为商购获得)、鲁比前列酮(可作为商购获得)、盐酸双环胺(可作为商购获得)、硫糖铝(可作为商购获得)、乳果糖(可作为商购获得)、多库酯(可作为商购获得)、巴柳氮二钠(可作为商购获得)、氯沙坦钾(可作为商购获得)、奥抑氮钠(可作为商购获得)、盐酸利眠宁、克利溴铵(可作为商购获得)、埃索美拉唑镁(可作为商购获得)、法莫替丁(可作为商购获得)、兰索拉唑(可作为商购获得)、兰索拉唑和萘普生(可作为Prevacid商购获得)、阿莫西林/克拉霉素/兰索拉唑(可作为商购获得)、奥美拉唑(可作为商购获得)、泮托拉唑钠(可作为商购获得)、盐酸胃复安(可作为或商购获得)、西咪替丁(可作为商购获得)、盐酸雷尼替丁(可作为商购获得)、和奥美拉唑、碳酸氢钠(可作为商购获得);利尿剂,包括螺内酯、氢氯噻嗪(可作为商购获得)、螺内酯(可作为商购获得)、布美他尼(可作为商购获得)、托拉塞米(可作为商购获得)、氯噻嗪(可作为商购获得)、速尿(可作为商购获得)、美托拉宗(可作为商购获得)和氢氯噻嗪、氨苯蝶啶(可作为商购获得)。
可用于本发明的活性剂还可包括治疗肺气肿的药物,诸如噻托溴铵(可作为商购获得);纤维肌痛药物,诸如盐酸米那普仑(可作为商购获得);用于治疗痛风的药物,诸如秋水仙碱(可作为商购获得)和非布索坦(febuxostat)(可作为商购获得);灌肠治疗,包括氨基水杨酸(可作为和商购获得);癫痫药物,包括丙戊酸(可作为商购获得)、非尔氨酯(可作为商购获得)、拉莫三嗪(可作为商购获得)、扑米酮(可作为商购获得)、奥卡西平(可作为商购获得)、唑尼沙胺(可作为商购获得)、左乙拉西坦(可作为商购获得)和苯妥英钠(可作为商购获得)。
可用于本文的勃起功能障碍疗法包括但不限于用于促进血液流向阴茎并用于实现自主神经活动的药物,诸如增加副交感神经(胆碱能)和减少交感神经(肾上腺素能)的药品。用于治疗勃起功能障碍的有用药剂包括例如作为以下可用的那些药剂:前列地尔(可作为商购获得)、他达拉非(可作为商购获得)、伐地那非(可作为商购获得)、阿朴吗啡(可作为商购获得)、盐酸育亨宾(可作为商购获得)和枸橼酸西地那非(可作为商购获得)。
本文可用的活性物质还可包括眼药和治疗剂,诸如盐酸地匹福林(可作为商购获得)、缬更昔洛韦(可作为商购获得)、更昔洛韦眼用凝胶(可作为商购获得);苯磺酸贝托司汀(可作为商购获得)、贝西沙星(可作为商购获得)、溴芬酸(可作为商购获得)、氟米龙(可作为商购获得)、盐酸毛果芸香碱(可作为商购获得)、环孢霉素(可作为商购获得)、酒石酸溴莫尼定(可作为Alphagan商购获得)、盐酸多佐胺/马来酸噻吗洛尔(可作为商购获得)、比马前列素(可作为商购获得)、马来酸噻吗洛尔(可作为商购获得)、曲伏前列素(可作为商购获得)、拉坦前列素(可作为商购获得)、碘磷灵(可作为Phospholine商购获得)、和兰尼单抗(可作为商购获得);流体控制剂,诸如乙酰唑胺(可作为商购获得);胆结石药物,包括熊二醇(可作为商购获得);用于治疗牙龈炎的药物,包括葡萄糖酸氯己定(可作为商购获得);头痛药物,包括布他比妥/磷酸可待因/阿司匹林/咖啡因(可作为与可待因商购获得)、盐酸那拉曲坦(可作为商购获得)、阿莫曲坦(可作为商购获得)、酒石酸麦角胺/咖啡因(可作为商购获得)、布他比妥/对乙酰氨基酚/咖啡因(可作为商购获得)、布他比妥/阿司匹林/咖啡因(可作为购得)、琥珀酸福伐曲坦(可作为商购获得)、苯甲酸利扎曲坦(可作为商购获得)、粘液酸异美汀/二氯醛比林/对乙酰氨基酚(可作为商购获得)、甲磺酸双氢麦角毒碱(可作为商购获得)、氢溴酸依来曲普坦(可作为商购获得)和佐米曲坦(可作为商购获得);流感药物,诸如嗜血杆菌b结合疫苗;破伤风类毒素缀合物(可作为商购获得);以及心脏治疗药,包括硫酸奎尼丁、二硝酸异山梨酯/盐酸肼苯哒嗪(可作为商购获得)、地高辛(可作为商购获得)、醋酸氟卡胺(可作为商购获得)、盐酸美西律(可作为商购获得)、磷酸丙吡胺(可作为商购获得)、盐酸普鲁卡因胺(可作为商购获得)和普罗帕酮(可作为商购获得)。
其他有用的活性物质包括肝炎治疗剂,包括恩替卡韦(可作为商购获得)、乙型肝炎免疫球蛋白(可作为HepaGam商购获得)、和利巴韦林(copegus/rebetol/ribasphere/vilona/virazole)(可作为商购获得);疱疹治疗剂,包括盐酸伐昔洛韦(可作为商购获得)、喷昔洛韦(可作为商购获得)、阿昔洛韦(可作为商购获得)、和泛昔洛韦(可作为商购获得);用于高血压的治疗剂,包括依那普利拉(可作为商购获得)、卡托普利(可作为商购获得)和赖诺普利(可作为商购获得)、盐酸维拉帕米(可作为商购获得)、雷米普利(可作为商购获得)、奥美沙坦酯(可作为商购获得)、氨氯地平/阿托伐他汀(可作为商购获得)、盐酸尼卡地平(可作为商购获得)、盐酸地尔硫卓(可作为商购获得为)、盐酸喹那普利(可作为商购获得)、盐酸喹那普利/氢氯噻嗪(可作为商购获得)、培哚普利叔丁胺盐(可作为商购获得)、坎地沙坦西酯(可作为商购获得)、坎地沙坦西酯/氢氯噻嗪(可作为Atacand商购获得)、厄贝沙坦/氢氯噻嗪(可作为商购获得)、厄贝沙坦(可作为商购获得)、苯磺酸氨氯地平/奥美沙坦酯(可作为商购获得)、盐酸左布诺洛尔(可作为商购获得)、盐酸倍他洛尔(可作为商购获得)、奈必洛尔(可作为商购获得)、卡托普利/氢氯噻嗪(可作为商购获得)、甲磺酸多沙唑嗪(可作为商购获得)、盐酸可乐定(可作为商购获得)、卡维地洛(可作为商购获得)、那多洛尔(可作为商购获得)、那多洛尔/苄氟噻嗪(可作为商购获得)、缬沙坦(可作为商购获得)、伊拉地平(可作为商购获得)、醋酸胍那苄(可作为商购获得)、盐酸胍法辛(可作为或商购获得)、氯沙坦钾/氢氯噻嗪(可作为商购获得)、盐酸普萘洛尔(可作为商购获得)、盐酸普萘洛尔/氢氯噻嗪(可作为商购获得)、依普利酮(可作为商购获得)、安贝生坦(可作为商购获得)、马来酸依那普利/非洛地平(可作为商购获得)、酒石酸美托洛尔(可作为商购获得)、盐酸贝那普利(可作为商购获得)、盐酸贝那普利/氢氯噻嗪(可作为Lotensin商购获得)、氨氯地平/盐酸贝那普利(可作为商购获得)、吲达帕胺(可作为商购获得)、群多普利(可作为商购获得)、替米沙坦(可作为商购获得)、替米沙坦/氢氯噻嗪(可作为Micardis商购获得)、盐酸哌唑嗪(可作为商购获得)、阿米洛利、氢氯噻嗪(可作为商购获得)、福辛普利钠(可作为ZZXT商购获得)、福辛普利钠/氢氯噻嗪(可作为商购获得)、吲哚洛尔(可作为商购获得)、非洛地平(可作为商购获得)、枸橼酸西地那非(可作为商购获得)、尼索地平(可作为商购获得)、群多普利/盐酸维拉帕米(可作为商购获得)、阿利吉仑(可作为商购获得)、甲磺酸依普罗沙坦(可作为商购获得)、甲磺酸依普罗沙坦/氢氯噻嗪(可作为Teveten商购获得)、盐酸莫昔普利/氢氯噻嗪(可作为商购获得)、盐酸莫昔普利(可作为商购获得)、马来酸依那普利/氢氯噻嗪(可作为商购获得)和赖诺普利/氢氯噻嗪(可作为商购获得)。
其他活性物质可用于治疗HIV/AIDS的药物中,诸如安普那韦(可作为商购获得)、替拉那韦(可作为商购获得),依非韦伦/恩曲他滨/替诺福韦(可作为商购获得)、拉米夫定/齐多夫定(可作为商购获得)、硫酸茚地那韦(可作为商购获得)、拉米夫定(可作为商购获得)、沙奎那韦(可作为商购获得)、扎西他滨(可作为商购获得)、洛匹那韦/利托那韦(可作为商购获得)、福沙那韦钙(可作为商购获得)、利托那韦(可作为商购获得)、齐多夫定(可作为商购获得)、硫酸阿扎那韦(可作为商购获得)、依非韦伦(可作为商购获得)、阿巴卡韦/拉米夫定/齐多夫定(可作为商购获得)、地达诺新(可作为商购获得)、甲磺酸奈非那韦(可作为商购获得)、奈韦拉平(可作为商购获得)、富马酸泰诺福韦二吡呋酯(可作为商购获得)、司他夫定(可作为商购获得)和硫酸阿巴卡韦(可作为商购获得);同型半胱氨酸去除剂,包括无水甜菜碱(可作为商购获得);药物,诸如胰岛素(可作为 和商购获得);和HPV治疗剂,诸如人乳头瘤病毒疫苗(可作为商购获得)或人二价乳头瘤病毒(可作为商购获得);免疫抑制剂,包括环孢霉素(可作为和商购获得)。
可用于本公开的活性物质还可包括催乳素抑制剂,诸如甲磺酸溴隐亭(可作为商购获得);用于辅助压力测试的药物,诸如瑞加德松(可作为商购获得);脱发药,包括非那雄胺(可作为和商购获得);胰腺炎治疗剂,诸如吉非罗齐(可作为商购获得);激素药物,诸如醋酸炔诺酮/乙炔雌二醇(可作为商购获得)、醋酸戈舍瑞林(可作为商购获得)、黄体酮凝胶(可作为商购获得)、黄体酮(可作为商购获得)、鲑鱼降钙素(可作为商购获得)、骨化三醇(可作为商购获得)、左甲状腺素(可作为 商购获得)、睾丸激素(可作为和商购获得);更年期药物,诸如雌二醇/醋酸炔诺酮(可作为商购获得)、屈螺酮/雌二醇(可作为商购获得)、雌二醇/左炔诺孕酮(可作为Climara商购获得)、雌二醇/醋酸炔诺酮(可作为商购获得)、雌二醇(可作为和商购获得)、酯化的雌激素和甲基睾酮(可作为商购获得)、雌激素(可作为 商购获得)、硫酸雌酮哌嗪(可作为商购获得)、结合雌激素(可作为商购获得)和醋酸甲羟孕酮(可作为商购获得);月经药物,包括醋酸亮丙瑞林(可作为Lupron Depot商购获得)、氨甲环酸(可作为商购获得)和醋酸炔诺酮(可作为商购获得);和肌肉松弛剂,包括盐酸环苯扎林(可作为商购获得)、替扎尼定(可作为商购获得)和硫酸莨菪碱(可作为商购获得)。
本文可用的活性物质还可包括骨质疏松药物,包括伊班膦酸钠(可作为商购获得)、利塞膦酸盐(可作为商购获得)、盐酸雷洛昔芬(可作为商购获得)和阿仑膦酸钠(可作为商购获得);排卵促进剂,包括枸橼酸氯芪酚胺(可作为商购获得);佩吉特氏病治疗剂,诸如依替膦酸二钠(可作为商购获得);胰酶缺乏症药物,诸如胰脂肪酶(可作为或商购获得);用于治疗帕金森氏病的药物,诸如盐酸普拉克索(可作为商购获得)、盐酸罗匹尼罗(可作为商购获得)、卡比多巴/左旋多巴(可作为Sinemet商购获得)、卡比多巴/左旋多巴/恩他卡朋(可作为商购获得)、盐酸司来吉兰(可作为商购获得)、雷沙吉兰(可作为商购获得)、恩他卡朋(可作为商购获得)和盐酸司来吉兰(可作为商购获得);多发性硬化症药物,诸如达伐吡啶(可作为商购获得)和干扰素β-I b(可作为商购获得);前列腺药物,包括氟他胺(可作为商购获得)、尼鲁米特(可作为商购获得)、度他雄胺(可作为商购获得)、盐酸坦索罗辛(可作为商购获得)、盐酸特拉唑嗪(可作为商购获得)和盐酸阿夫唑嗪(可作为商购获得)。
活性物质还可包括精神药物、包括阿普唑仑(可作为购得)、氯扎平(clozopin)(可作为购得)、氟哌啶醇(可作为购得)、盐酸氟西汀(可作为购得)、盐酸舍曲林(可作为购得)、阿塞那平(可作为商购获得)、伊潘立酮(可作为商购获得)、盐酸帕罗西汀(可作为商购获得)、阿立哌唑(可作为商购获得)、胍法辛(可作为商购获得)、苯丙胺和甲基苯丙胺(可作为和商购获得)、盐酸氯米帕明(可作为商购获得)、盐酸丁螺环酮(可作为商购获得)、氢溴酸西酞普兰(可作为商购获得)、盐酸度洛西汀(可作为商购获得)、哌醋甲酯(可作为Ritalin、商购获得)、双丙戊酸钠(丙戊酸)(可作为商购获得)、硫酸右旋安非他命(可作为商购获得)、盐酸文拉法辛(可作为商购获得)、司来吉兰(可作为商购获得)、卡马西平(可作为商购获得)、碳酸锂(可作为商购获得)、马来酸氟伏沙明/盐酸右哌甲酯(可作为商购获得)、盐酸齐拉西酮(可作为商购获得)、甲磺酸双氢麦角碱(可作为商购获得)、草酸艾司西酞普兰(可作为商购获得)、利眠宁(可作为商购获得)、盐酸吗茚酮(可作为商购获得)、硫酸苯乙嗪(可作为商购获得)、替沃噻吨(可作为商购获得)、盐酸地昔帕明(可作为商购获得)、苯二氮卓类(诸如可作为获得的那些)、盐酸去甲替林(可作为商购获得)、硫酸环丙胺(可作为商购获得)、普鲁氯嗪、米氮平(可作为商购获得)、利培酮(可作为商购获得)、富马酸喹硫平(可作为商购获得)、盐酸多塞平(可作为商购获得)、盐酸托莫西汀(可作为商购获得)、马来酸曲米帕明(可作为商购获得)、奥氮平/盐酸氟西汀(可作为商购获得)、盐酸丙咪嗪(可作为商购获得)、盐酸普罗替林(可作为商购获得)、盐酸安非他酮(可作为Wellbutrin和Wellbutrin商购获得)和奥氮平(可作为商购获得)。
可用于本文的活性剂还可包括尿酸减少治疗药、包括别嘌醇(可作为商购获得);癫痫发作药物、包括加巴喷丁(可作为商购获得)、乙苯妥英(可作为商购获得)、氨己烯酸(可作为商购获得)和托吡酯(可作为商购获得);带状疱疹治疗药、诸如带状疱疹病毒活痘苗(可作为商购获得);皮肤护理药物、包括卡泊三醇(可作为商购获得)、优特克单抗(可作为商购获得)、特拉万星(可作为商购获得)、异维甲酸(可作为商购获得)、氢化可的松/双碘喹啉(可作为商购获得)、磺胺醋酰钠/硫(可作为商购获得)、壬二酸(可作为商购获得)、过氧化苯甲酰(可作为商购获得)、阿达帕林(可作为商购获得)、氟脲嘧啶(可作为商购获得)、匹美莫司(可作为商购获得)、局部用红霉素(可作为 商购获得)、氢化可的松(可作为商购获得)、甲硝唑(可作为商购获得)、强力霉素(可作为商购获得)、维甲酸(可作为和商购获得)、对甲氧酚/维甲酸(可作为商购获得)、阿维A酸(可作为商购获得)、水合钙泊三醇/二丙酸倍他米松(可作为商购获得)、他扎罗汀(可作为商购获得)、氟轻松醋酸酯(可作为商购获得)、地奈德(可作为商购获得)、硝酸咪康唑/氧化锌(可作为商购获得)、酮康唑(可作为商购获得)和依法珠单抗(可作为商购获得)。
可用于本文的其他活性物质可包括睡眠障碍药物、包括扎来普仑(zaleplon)(可作为购得)、右旋佐匹克隆(可作为购得)、酒石酸唑吡坦(可作为Ambien商购获得)、劳拉西泮(可作为商购获得)、盐酸氟西泮(可作为商购获得)、三唑仑(可作为商购获得)、氯硝西泮(可作为商购获得)、巴比妥类药物(可作为商购获得)、莫达非尼(可作为商购获得)、羟基安定(可作为商购获得)、瑞美替昂(可作为商购获得)、二钾氯氮(可作为商购获得)、地西泮(可作为商购获得)、夸西泮(可作为商购获得)和艾司唑仑(可作为商购获得);戒烟药物、诸如伐尼克兰(可作为商购获得)、尼古丁(诸如)和盐酸安非他酮(可作为商购获得);和类固醇、包括二丙酸阿氯米松(可作为商购获得)、二丙酸倍他米松(可作为商购获得)、糠酸莫米松(可作为商购获得)、氟替卡松(可作为FloventFlovent商购获得)、氟轻松醋酸酯(可作为商购获得)、糠酸莫米松一水合物(可作为商购获得)、去羟米松(可作为商购获得)、克霉唑/二丙酸倍他米(可作为商购获得)、醋酸泼尼松龙(可作为Pred BudesonideRhinocort商购获得)、氢化泼尼松磷酸钠(可作为商购获得)、地索奈德(可作为商购获得)和卤倍他索丙酸酯(可作为商购获得)。
其他活性物质可用于甲状腺疾病治疗、诸如激素TC和TD(可作为Armour商购获得);钾缺乏症治疗、包括氯化钾(可作为商购获得);甘油三酸酯调节剂、包括ω-3酸乙酯(可作为商购获得);泌尿药物、诸如盐酸非那吡啶(可作为商购获得)和乌洛托品、亚甲基蓝/水杨酸苯酯/苯甲酸/硫酸阿托品/莨菪碱(可作为商购获得);孕妇维生素(可作为AdvancedPrenate商购获得);体重控制药物、包括奥利司他(可作为商购获得)和盐酸西布曲明(可作为商购获得)。
预期用于本文的流行的H2拮抗剂包括西咪替丁、盐酸雷尼替丁、法莫替丁、尼扎替丁、乙溴替丁、咪芬替丁、罗沙替丁、皮沙替丁(pisatidine)和罗沙替丁乙酸酯(aceroxatidine)。
活性抗酸成分包括但不限于以下物质:氢氧化铝、氨基乙酸二羟基铝、氨基乙酸、磷酸铝、二羟碳酸铝钠、碳酸氢盐、铝酸铋、碳酸铋、碱式碳酸铋、次没食子酸铋、次硝酸铋、水杨酸亚铋、碳酸钙、磷酸钙、柠檬酸根离子(酸或盐)、氨基乙酸、水合硫酸铝镁、氢氧化镁铝、硅酸镁铝、碳酸镁、甘氨酸镁、氢氧化镁、氧化镁、三硅酸镁、乳固体、单或双盐基磷酸钙铝(aluminum mono-ordibasic calcium phosphate)、磷酸三钙、碳酸氢钾、酒石酸钠、碳酸氢钠、铝硅酸镁、酒石酸和盐。
本发明中次用的药物活性剂可包括过敏原或抗原、诸如但不限于来自草、树或豚草的植物花粉;和动物皮屑、其为从猫和其他有毛动物的皮肤和毛发上掉下来的微小鳞屑;昆虫、诸如屋尘螨、蜜蜂和黄蜂;和药物、诸如青霉素。
具体活性物质的示例包括但不限于16-α氟代雌二醇、16-α-吉妥辛、16-表雌三醇、17α二氢雌二醇、17α雌二醇、17β雌二醇、17羟基孕酮、1α-羟基维生素D2、1-十二烷基吡咯烷酮、20-表-1,25-二羟基维生素D3、22-氧代化骨化三醇、2CVV、2′-nor-cGMP、3-异丁基GABA、5-乙炔基尿嘧啶、6-FUDCA、7-甲氧基他克林、阿维菌素、阿巴诺喹、阿贝卡尔、阿比特龙、阿鲁司特、阿鲁司特钠、阿卡地辛、阿坎酸、阿卡波糖、醋丁洛尔、盐酸乙酰卡尼、醋克立定、乙酰氯芬酸、醋氨苯砜、醋谷胺铝、乙酰吗喃、对乙酰氨基酚、乙酰唑胺、乙酰苯磺酰环己脲、醋羟胺酸、acetomepregenol、马来酸醋奋乃静、磺胺苯砜钠、氯化乙酰胆碱、乙酰半胱氨酸、乙酰左旋肉碱、醋美沙朵、阿昔呋喃、阿西莫司、阿昔替酯、阿维A酸、阿西维辛、阿柔比星、阿克吐、盐酸阿可达佐、阿考烟肼、吖啶琐辛、阿伐斯汀、阿克罗宁、阿克索胺、阿托地近、阿昔洛韦、酰基夫文、金刚芬酯、阿达帕林、阿达帕林、阿达色林、盐酸阿达色林、腺环戊醇、腺环戊醇、阿德福韦、阿地米屈、腺苷蛋氨酸、腺苷、阿的纳唑仑、盐酸阿地芬宁、人降脂素(adiposin)、阿多来新、阿屈非尼、肾上腺酮、airbutamine、阿拉普利、阿来霉素、丙氨酸、阿拉丙酯、alaptide、阿苯达唑、白唇竹叶青素、沙丁胺醇、Alclofenae、铝克洛沙、aldecalmycin、阿地白介素、尿囊素铝、盐酸烯丙苯乙胺、阿伦膦酸盐、阿仑膦酸钠、阿仑棒酸、阿仑替莫、盐酸阿仑替莫、阿库氯铵、阿来西定、α-骨化醇、阿夫唑嗪、阿孕奈德、阿糖脑苷酶、阿列氟烷、阿利那斯汀、醋美沙朵、阿利帕胺、阿利吉仓、尿囊素、二丙烯基巴比妥、别嘌呤醇、阿洛米酮、阿洛司琼、盐酸阿洛司琼、阿洛夫定、阿尔哌汀、αidosone、阿吡坦、阿普唑仑、盐酸烯丙心安、盐酸阿普诺辛、前列地尔、阿司他丁钠、酒石酸阿坦色林、阿替普酶、阿尔噻嗪、六甲蜜胺、阿托霉素B、柠檬酸Alverinc、爱维莫潘、阿韦舒托、醋酸阿马地酮、盐酸金刚烷胺、氨莫司汀、安波霉素、安立生坦、安布鲁星、安布茶碱、安布赛特、安西法尔、安西奈德、氮卓西林、氮卓西林酯、盐酸氨甲达林、阿洛米松、氨托利、安麦角、醋酸阿美蒽醌、甲硫阿美铵、安非他酮、氨芬酸钠、氨氟替唑、阿米环素、甲磺酸Amidephrine、amidox、氨氟沙星、氨磷汀、Amikacin、盐酸阿米洛利、盐酸氨基吖啶、氨苯甲酸钾、氨基苯甲酸钠、氨基己酸、氨鲁米特、氨基马尿酸钠、氨基乙酰丙酸、氨茶碱、阿米雷司、氨基水杨酸钠、氨基水杨酸、胺碘酮、盐酸氨普立糖、盐酸氨喹新、阿米舒必利、双甲脒、盐酸阿米替林、氨来咕诺、氨氯地平、甲磺酸氨氯地平、异戊巴比妥钠、阿莫地喹、盐酸阿莫地喹、阿莫罗芬、阿莫沙平、阿莫西林、胺苯氯醛、苯丙胺、硫酸苯丙胺、安福霉素、两性蛋白B、氨苄青霉素、ampiroxicam、硫酸二甲胺嗪、氨喹酯、氨力农、氨柔比星、安吖啶、淀粉酶、淀粉不溶素、amythiamicin、醋酸阿那孕酮、阿那格雷、阿那白滞素、ananain,阿那立肽、醋酸阿那立肽、阿那曲唑、阿那佐林钠、安克洛酶、穿心莲内酯、雄烯二酮、血管紧张素酰胺、阿尼多昔、阿尼利定、盐酸阿尼洛泮、阿尼西坦、阿尼罗酸、甲溴辛托品、阿尼普酶、阿尼普酶、双炔失碳酯、拮抗剂D、拮抗剂G、安雷利克斯、磷酸安他唑啉、抗蠕霉素、蒽林、安曲霉素、抗雄激素、抗雌激素、抗瘤酮、安替比林、反义寡核苷酸、阿帕多林、阿帕泛、阿帕西林钠、阿帕茶碱、阿扎丙宗、甘氨酸阿非迪霉素、Apixifylline、盐酸阿扑吗啡、阿可乐宁、盐酸阿可乐宁、安普、阿普林定、盐酸阿普林定、阿普硫钠、抑肽酶、马来酸阿普氮平、阿替加奈、嘌呤酸、嘌呤酸、阿雷地平、阿拉诺丁、阿巴前列素、arbekicin,阿比朵尔、盐酸阿布他明、阿氯苯宁、阿地肝素钠、阿加曲班、精氨酸、鞣酸精氨加压素、阿立酮、阿立哌唑、阿莫非尼、阿罗洛尔、Arpinocid、阿替夫林、富马酸阿替利特、阿西马朵林、aspalatone,天冬酰胺酶、天门冬氨酸、门冬托星、asperfuran、阿司匹林、阿扑西林、Asprelin、息斯敏、硫酸阿司米星、asulacrine、阿他美坦、阿扎那韦、氨酰心安、阿替韦啶、阿替美唑、马来酸阿替丙嗪、阿托利特、托莫西汀、阿托伐他汀、阿托伐他汀钙、阿托西班、阿托伐醌、atpeninB、苯磺阿曲库铵、阿莫司汀、阿曲肌醇、阿托品、硫酸阿托品、金诺芬、金担子素A、金硫葡糖、卑霉素、阿伏霉素、阿夫立定、尼扎替丁、axinastatin 1、axinastatin 2、axinastatin 3、阿扎苯胺、Azacitidinie、盐酸氮氯嗪、阿扎康唑、azadirachtine、二盐酸阿扎兰司他、富马酸阿扎克生、马来酸阿扎那托、阿扎硝唑、阿扎哌隆、阿扎立平、重氮乙酰丝氨酸、阿扎司琼、马来酸阿扎他定、硫唑嘌呤、硫唑嘌呤钠、阿扎毒素、重氮酪氨酸、壬二酸、氮卓斯汀、阿折地平、氮卓吲哚、阿扎替派、阿齐利特、阿奇霉素、阿洛西林、阿佐利明、阿佐塞米、阿佐霉素、氨曲南、阿珠莫林钠、盐酸巴氨西林、巴卡亭III、杆菌肽、巴氯芬、假马齿苋皂素A、假马齿苋皂素B、bactobolamine、balanol、巴拉齐朋、balhimycin、巴洛沙星、巴柳氮、班贝霉素、班布特罗、硫酸巴美生、盐酸巴米茶碱、班硝唑、宝藿甙1、巴马斯汀、巴尼地平、次水杨酸铋、巴西芬净、盐酸巴他必利、巴布司特、马来酸巴替拉平、巴马司他、白僵菌素、盐酸胺甲噻吨酮、贝卡普勒明、贝康唑、二丙酸氯地米松、贝氟沙通、Beinserazide,贝磷地尔、颠茄、贝洛酰胺、贝美司琼、贝米曲啶、贝莫拉旦、盐酸贝那利秦、贝那普利、盐酸贝那普利、贝那普利拉、苯达洛尔加磺酸盐、盐酸苯达莫司汀、苄达酸、苄氟噻嗪、本芴醇、贝尼地平、贝诺睾酮、苯噁洛芬、苯噁洛芬、盐酸奥布卡因、苯哌利多、苯他西泮、苯替酪胺、贝奴司他、苯溴马隆、苄索氯铵、盐酸苄替米特、苯咯溴铵、盐酸苄吲吡林、苯异噁唑、苯佐卡因、苯佐利定、盐酸苯佐他明、苯佐替派、benzoidazoxan、苯佐那酯、过氧苯甲酰、苯沙酸钙、benzoylstaurosporine、苯喹胺、苄噻嗪、苯扎托品、甲磺酸苄托品、盐酸苄达明、苯甲酸青霉噻唑酰多赖氨酸、苄普地尔、盐酸苄普地尔、贝拉康坦、贝前列素、贝瑞福林、柏拉非农、柏托沙米、去氧红霉素、贝西吡啶、βalethine、βclamycin B、倍他米松、倍他米隆、倍他洛尔、盐酸倍他洛尔、胆碱氯化物、硫酸倍他尼定、桦木酸、贝伐单抗、贝凡洛尔、盐酸贝凡洛尔、苯扎贝特、盐酸比拉米可、比阿培南、比卡鲁胺、盐酸比西发定、盐酸二氯地尔、比地索胺、二苯美仑、联苯苄唑、比卡林、比马前列素、bimithil、宾达利、比尼霉素、比螺酮、bioxalomycinα2、盐酸比培那醇、比哌立登、苯柳胺酯盐酸、比立哌隆、比生群、比沙雷米、bisaziridinylspermine、双苯并咪唑A、双苯并咪唑B、双奈法德、乳酸比索布啉、比索洛尔、富马酸比索洛尔、硫酸镁双巯氧吡啶、bistramide D、bistramide K、bistrateneA、硫双二氯酚钠、十一碳烯酸去甲睾酮、乙雌异烯醇、勃金刚酯、波吲洛尔、波生坦、肉毒杆菌毒素、波克昔定、布雷菲德菌素、breflate、布喹那钠、溴他西尼、甲苯磺酸溴苄胺、盐酸布芬太尼、溴莫尼定、纤酶、溴克立新、溴克利那、溴苯噁嗪酮、马来酸溴朵林、溴西泮、溴氯唑酮、菠萝蛋白酶、溴芬酸、Brominidione、溴隐亭、盐酸溴苯醇胺、溴沙尼特、溴哌利多、癸酸溴哌利多、马来酸溴苯那敏、溴哌莫、溴匹立明、溴替唑仑、马来酸布卡尼、布新洛尔、盐酸布克力嗪、布色酮、布地奈德、布地品、布度钛、丁福明、布美他尼、布那司特、布那唑嗪、盐酸布诺洛尔、丁吡考胺、盐酸布比卡因、丁丙诺啡、盐酸丁丙诺啡、安非他酮、氢溴酸安非他酮、盐酸安非他酮、布拉氨酯、醋酸布舍瑞林、盐酸丁螺环酮、白消安、仲丁巴比妥、布他西丁、盐酸布他拉莫、布他比妥、氨苯丁酯、柠檬酸布他米酯、布他哌嗪、布他前列素、布替膦酸四钠、布替萘芬、布替利嗪、buthionine sulfoximine、布替卡星、丁苯宁、硫酸布替罗星、布替西雷、丙酸布替可特、硝酸康唑盐、布托酯、布托巴胺、盐酸布托丙茚、布托啡诺、盐酸布托沙明、盐酸布替林、卡麦角林、放线菌素C、卡地姆、碘、咖啡因、红厚壳属植物提取物A、骨化二醇、卡泊三醇、卡泊三醇、降钙素、骨化三醇、十一碳烯酸钙、钙磷酸蛋白C、卡普睾酮、坎苯达唑、卡莫格雷、喜树碱衍生物、卡格列净、金丝雀痘IL-2、坎地沙坦、坎地沙坦酯、克念菌素、坎沙曲、坎沙曲拉、Caniglibose、坎利酸钾、坎利酮、卡培他滨、克冠酸钠、克冠酸、硫酸卷曲霉素、卡罗单抗、辣椒素、卡托普利、卡普脲、羧甲司坦、卡醋胺、卡巴胆碱、卡巴多司、卡马西平、过氧化氢脲、十二烷基硫酸氯苯戊氨脲、卡巴匹林钙、卡巴折伦、咔唑霉素C、羧苄青霉素钾、甘珀酸钠、卡贝替姆、卡贝缩宫素、卡比多巴、卡比多巴、左旋多巴、马来酸卡比沙明、盐酸卡必芬、卡波氯醛、石炭酸、品红、卡钼、卡孕、卡波佛、羧酰胺_氨基-三唑、羧氨基三唑、羧甲基β-1、3-葡聚糖、盐酸卡布特罗、CaRestΜ3、柠檬酸卡芬太尼、卡立普多、卡金刚酸、卡氮芥、CARN700、卡硝唑、卡罗沙酮、卡培立肽、马来酸丙酰奋乃静、卡洛芬、琥珀酸卡沙群、卡它唑酯[、卡替洛尔、盐酸卡替洛尔、盐酸卡柔比星、卡维地洛、卡伏曲林、盐酸卡伏曲林、卡折来新、卡泊芬净(ICOS)、澳粟精胺、caurumonam、西巴西坦、抗菌肽B、西地芬戈、头孢克洛、头孢羟氨苄、头孢孟多、头孢帕罗、头孢曲秦、头孢氮氟钠、头孢唑啉、头孢卡品酯、甲苯磺酸喷替头孢达肟、头孢地尼、头孢托仑酯、头孢吡肟、头孢他美、头孢替考、头孢克肟、头孢瑞南、盐酸头孢甲肟、头孢美唑、头孢米诺、头孢地嗪、头孢尼西钠、头孢哌酮、头孢哌酮钠、头孢雷特、头孢噻利、头孢噻肟钠、头孢替坦、头孢替安、头孢西丁、头孢唑兰、头孢咪唑、头孢匹胺、头孢匹罗、头孢泊肟酯、头孢丙烯、头孢沙定、头孢磺啶、头孢他啶、头孢特仑、头孢布烯、头孢唑肟钠、ceftriaxone、头孢呋辛、雷公藤红素、塞来昔布、celikalim、塞利洛尔、cepacidiineA、头孢乙腈钠、头孢氨苄、头孢甘酸、头孢噻啶、头孢噻吩钠、头孢匹林钠、头孢拉定、西文氯胺、西立伐他汀、蛙皮素、西罗普利、培化舍珠单抗、舍托肝素钠、西他苯钠、西他氯铵、盐酸塞他洛尔、Cethuperazone、西替地尔、西替利嗪、乙酰霉素、盐酸西曲酸酯、盐酸塞替利嗪、西曲瑞克、西妥昔单抗、氯化十六烷基吡啶、鹅脱氧胆酸、盐酸氯酚二苯胺醇、氯醛甜菜碱、苯丁酸氮芥、氯霉素、氯海因、利眠宁、葡萄糖酸氯己定、二氢卟酚、醋酸氯地孕酮、chloroorienticin A、盐酸氯普鲁卡因、Chloropropamide、氯喹、chloroquinoxalinesulfonamide、氯噻嗪、氯烯雌醚、二氯羟喹、氯二甲酚、马来酸氯苯那敏、氯苯甘油氨酯、马来酸氯苯那敏、氯丙嗪、盐酸氯丙嗪、氯磺丙脲、氯普噻吨、硫酸氢金霉素、氯噻酮、氯唑沙宗、消胆胺树脂、盐酸卡波罗孟、西苯唑啉、西卡前列素、盐酸环拉福林、苯嘧吲哚、环索奈德、西氯他宁、环吡酮、环洛芬、环丙洛尔、西多福韦、盐酸西多塞平、西苯唑啉、环格列酮、盐酸西拉多巴、西兰司琼、西司他丁、西司他丁钠、西拉普利、西尼地平、甲磺酸西洛巴明、西洛雷定、西洛芬净、西洛他唑、西马特罗、西咪替丁、西托溴铵、钙模拟物药物、西那司特、盐酸辛那色林、马来酸桂哌酯、环桂氟胺、烯孕醇、西尼必利、桂美君、桂利嗪、西诺西泮、西诺沙星、桂哌林、桂溴胺、辛喷他宗、辛曲胺、塞奥罗奈、西潘茶碱、琥珀酸环丙法朵、环丙奈德、环丙贝特、环丙沙星、西前列烯、西拉马朵、西罗霉素、顺钼、西沙必利、苯磺顺阿曲库胺、顺康唑、顺卟啉、西替克新、西酞普兰、氢溴酸西酞普兰、西替酰胺、胞二磷胆碱、citreamicinα、克拉屈滨、盐酸氯胺羟喹、克拉霉素、黄皮酰胺、克拉维酸钾、克拉唑仑、氯苯唑胺、氯波必利、氯马斯汀、马来酸克仑硫卓、克利溴铵、克林沙星、克林霉素、盐酸克林霉素、氯碘羟喹、氯碘沙尼、克利洛芬、氯巴占、丙酸氯倍他索、丁酸氯倍他松、醋酸氯可托龙、氯达诺林、盐酸氯达酮、氯膦酸、氯法齐明、安妥明、磷酸氯非铵、醋酸氯孕酮、磷酸氯马克仑、醋酸氯美孕酮、氯甲孕酮、氯甲噻唑、氯米芬类似物、氯氨雷司、克罗米酚、盐酸氯米帕明、氯硝西泮、可乐定、盐酸可乐定、氯硝甘油、氯尼塞利、氯尼辛、氯帕胺、氯哌噻吨、盐酸氯哌喹酮、氯吡格雷、硫酸氢氯吡格雷、氯哌莫齐、甲磺酸氯哌帕生、氯吡酸、氯泼尼醇、氯前列烯醇钠、二钾氯氮卓氯乙双酯、氯索隆、盐酸氯哌隆、盐酸氯丙那林、氯舒隆、盐酸氯特胺、氯氰柳胺、乙酰甘氨酸氯西拉敏、氯噻平、马来氯胺噻吨、丙酸氯硫卡松、克霉唑、苄星邻氯青霉素、邻氯青霉素钠、氯羟喹、氯氮平、阿莫西林棒酸钾合剂、可卡因、球孢菌素、可待因、磷酸可待因、可多克辛、秋水仙素、考来替兰、盐酸考来替泊、考来酮、考福新、棕榈酸考福西利、粘菌素甲磺钠、硫酸粘菌素、collismycin A、collismycin B,甲磺酸可尔特罗、考布他汀A4、complestatin、conagenin、盐酸Conorphone、考替特罗、contortrostatin,醋酸可米松、可的瑞林Ovine Triflutate、促肾上腺皮质激素、可的松、醋酸可的伐唑、可托多松、cosalane,costatolide、合成促皮质素、可替宁、香豆定、香豆霉素、crambescidin 816、克伐他汀、克立那托、克罗米腈钠、色甘酸钠、克罗米通、cryptophycin 8、cucumariosid、铜迈星、curacin A、硫酸凝胶多糖、curiosin、环青霉素、环唑嗪、环HPMPC、胺氢咔唑、马来酸赛利拉敏、赛克力嗪、环苯达唑、环苯扎林、环丁基甲酸A、环丁基甲酸G、cyclocapron、双羟萘酸环氯弧、放线菌酮、cyclopentanthraquinones、环戊噻嗪、盐酸环喷托酯、盐酸环丙奋乃静、环磷酰胺、cycloplatam、环丙烧、环丝氨酸、cyclosin、环孢素、cyclothialidine、环噻嗪、cyclothiazomycin、环庚米特、cypemycin、盐酸Cyponamine、环丙西泮、盐酸赛庚啶、盐酸环丙利多、环丙孕酮、环丙米特、半胱胺、盐酸半胱氨酸、胱氨酸、阿糖胞苷、盐酸阿糖胞苷、阿糖胞苷ocfosfate、细胞松弛素B、磷酸己烷雌酚、达卡巴嗪、达昔单抗、达替咪星、更生霉素、大豆黄素、苯磺酸达来达林、达福普汀、达肝素钠、达曲班、达伐他汀、达那肝素、达那唑、丹曲林、daphlnodorin A、达哌唑、达匹坦、盐酸达泊西汀、氨苯砜、达托霉素、达促红素α、达格列酮钠、达非那新、darlucin A、达罗地平、达西多明、盐酸柔红霉素、马来酸达扎醇、盐酸氮卓尼尔、达美格雷、富马酸达佐必利、盐酸达唑氧苯、硫酸异喹胍、地西他滨、去铁酮、地夫可特、去氧胆酸、dehydrodidemnin B、去氢表雄酮、地拉普利、盐酸地拉普利、甲磺酸地拉韦定、地来夸明、地发哌嗪、醋酸地马孕酮、地莫匹醇、飞燕草甙元、地美溴铵、地美环素、去甲环素、地莫西泮、地奴真菌素、脱氧吡啶啉、双丙戊酸钠、地泼罗酮、地前列素、depsidomycin,德伦环烷、硫酸皮肤素、地昔洛韦、地西奈德、地氟醚、盐酸地昔帕明、地西卢定、去乙酰毛花苷、地洛他定、地洛瑞林、去氨加压素、硫酸去氨加压素、去氧孕烯、地奈德、去羟米松、desoxoamiodarone,醋酸去氧皮质酮、酒石酸detajmium、盐酸地特诺、醋酸地肽瑞里、地伐西匹、地塞米松、右旋米唑、马来酸右氯苯那敏、马来酸右氯苯那敏、盐酸环庚吡奎醇、右苄替米特、盐酸右芬氟拉明、dexifosfamide、苯双咪唑、右酮洛芬、右氯谷胺、美托咪啶、右奥马钼、盐酸右奥沙屈、右泛醇、右培美酸、盐酸右普萘洛尔、右雷佐生、右索他洛尔、糊精2-硫酸、右旋苯丙胺、右美沙芬、盐酸右啡烷、右甲状腺素钠、右维拉帕米、地扎胍宁、地秦胺、地佐辛、盐酸二醋洛尔、环己氨磺酸二胺卡因、氯氨磺苯酰胺、泛影葡、泛影酸、二氨藜芦啶、地西泮、地吖醌、二氮嗪、盐酸二苯西平、二苯并噻吩、二丁卡因、Dichliorvos、氯醛比林、二氯磺胺、地西利酮、双氯芬酸、双氯芬酸钠、双氯西林、dicranin、双香豆素、盐酸双环胺、去羟肌苷、代代宁B、didox,己二烯雌酚、地诺孕素、柠檬酸乙胺嗪、diethylhomospermine、diethylnorspermine、盐酸安非拉酮、己烯雌酚、盐酸氰苯哌酰胺、地芬诺辛、双醋二氟拉松、盐酸二氟沙星、盐酸Difluanine、二氟可龙、二氟米酮钠、二氟尼柳、二氟泼尼酯、地弗他酮、洋地黄、洋地黄毒苷、地高辛、盐酸双己维林、二受体激动剂、二氢-5-氮胞苷、双氢酒石酸、甲磺酸二氢麦角胺、Dihydroestosterone、硫酸双氢链霉素、二氢速留醇、苯妥英钠、盐酸地来洛尔、盐酸地尔硫卓、二甲法登、盐酸二甲弗林、晕海宁、二巯丙醇、二甲双酮、马来酸二甲茚定、地美炔酮、二甲基亚砜、二甲基同型精胺(dimethylhomospermine)、二甲基前列腺素铝、地来西坦、盐酸Dimoxamine、地诺前列素、地诺前列酮、盐酸地奥沙屈、dioxamycin、苯海拉明、苯海拉明柠檬酸、地芬尼多、盐酸地芬诺酯、diphenylspiromustine、盐酸地匹福林、地匹福林、dipliencyprone、地丙苯酮、dipropylnorspermine、潘生丁、双吡硫翁、安乃近、地红霉素、discodermolide、地索布胺、地索苯宁、丙吡胺、二噁沙利、戒酒硫、地替吉仑、双丙戊酸钠、地佐环平马来酸、多巴酚丁胺、多卡巴胺、多西苯醌、多西紫杉醇、多康唑、二十二烷醇、多非利特、多拉司琼、多奈哌齐、多尼培南、多佐胺、多沙唑嗪、甲磺酸多沙唑嗪、doxycydine、屈螺酮、度洛西汀、度他雄胺、依巴斯汀、依比拉肽、乙溴替丁、依布硒、依卡派特、依卡倍特、依卡曲尔、ecdisteron,echicetin、锯鳞(蝮蝰)血抑(环)肽、碘依可酯、马来酸依氯那明、乙唑司特、依考莫司汀、益康唑、海鞘素722、依库珠单抗、依达拉奉、依达曲沙、依地福新、醋酸依地福龙、埃巴单抗、依度尿苷、依决洛单抗、依酚氯铵、醋酸edroxyprogesteone、依法韦仑、依非加群、依氟鸟氨酸、依福地平、egualcen、依兰群、eleatonin、榄香烯、依立曲坦、依高地平、依利罗地、依沙芦星、eltenae、依鲁卡因、emailcalim、依美斯汀、盐酸吐根碱、乙格列酯、甲苯磺酸Emilium、乙嘧替氟、依莫白介素、恩曲他滨、盐酸依那朵林、Enailciren、依那普利、马来酸依那普利、依那扎群、恩环丙酯、甲磺酸恩屈嗪、甲地松、安氟醚、恩格列酮、恩康唑、依尼前列素、恩莫单抗、恩洛钼、乙诺司特、依诺利康钠、依诺沙星、依诺沙星、依诺肝素钠、依诺肝素钠、依诺昔酮、磷酸恩哌罗林、恩丙茶碱、恩普氨酯、恩他卡朋、肠抑素、恩韦拉登、恩韦肟、麻黄碱、依匹西林、表美雌醇、肾上腺素、硼酸Epinephryl、依匹哌啶、依匹唑、表阿霉素、盐酸差向四环素、依匹噻嗪、促红细胞生成素α、促红细胞生成素的β、依前列醇、依前列醇钠、epoxymexrenone、爱普列特、依普沙坦、依斯的明、去氢马烯雌酮、马烯雌酮、厄布洛唑、厄多司坦、甲磺酰麦角碱、马来酸麦角新碱、酒石酸麦角胺、厄洛替尼、艾生利特、厄索夫明、赤藓糖醇、赤鲜醇四硝酸酯、红霉素、促血红细胞生长素、艾司西酞普兰、盐酸艾司洛尔、埃索美拉唑、盐酸依索比星、盐酸乙硫酰丙喹、舒乐安定、雌二醇、雌莫司汀、雌秦醇氢溴酸、雌三醇、雌呋酯、雌激素、雌酮、哌嗪雌酮硫酯、乙磺普隆、艾司佐匹克隆、盐酸乙非君、依那西普、依他硝唑、依坦特罗、依他洛汀、盐酸依他唑酯、依特比妥、乙沙西嗪、利尿酸钠、利尿酸、盐酸乙胺丁醇、香草二乙胺、乙醇胺油酸、Ethehlorvynol、盐酸Ethembutol、炔雌醇、乙碘油、乙硫异烟胺、硝酸依托南、盐酸普罗吩胺、乙琥胺、乙琥胺、乙苯妥英、盐酸乙氧二氨偶氮苯、乙苄托品、氯乙烷、地布酸乙酯、乙雌烯醇、Ethyndiol、去氢氯炔诺酮、乙炔雌二醇、双醋炔诺醇、依苯达唑、依替卡因、依替膦酸二钠、依替膦酸、依替菲宁、盐酸依汀替丁、依替唑仑、依托度酸、依托芬那酯、盐酸依托福明、依托咪酯、依托孕烯、盐酸依托哌酮、依托泊苷、氯苯乙嘧胺、艾托考昔、盐酸乙苯噁啶、依托唑啉、依曲巴明、依曲韦林、依曲替酯、醋酸乙色胺、盐酸尤卡托品、丁香酚、盐酸尤普罗辛、eveminomicin、依沙美肟、艾沙瑞林、盐酸己丙洛尔、依西美坦、法倔唑、faeriefungin、泛昔洛韦、法莫替丁、氨吡啶、泛托法隆、盐酸泛曲酮、法罗培南、法西多曲、法舒地尔、法扎拉滨、非多托秦、非氨酯、非氨酯、联苯乙酸、非洛地平、苯赖加压素、非那拉胺、非那莫、芬苯达唑、芬布芬、芬西布醇、芬氯酸、芬克洛宁、苯克洛酸、芬度柳、芬雌酸、盐酸苯丙胺乙茶碱、盐酸芬氟拉明、酚加宾、非尼米特、非尼雷司、盐酸氯苯氧甲唑、苯甲吗酮、非诺班、硫酸苯辛替明、非诺贝特、非诺多泮、非诺洛芬、非诺特罗、苯吡噁二酮、盐酸苯呤司特、芬前列林、芬喹唑、芬维A胺、芬司匹利、芬太尼、枸橼酸芬太尼、芬替酸、芬替克洛、芬替康唑、盐酸非尼啶醇、非普地醇、ferpifosate钠、ferristene、ferrixan、硫酸亚铁、干燥的、超顺磁性氧化铁、非莫西尔、盐酸非托西酯、非索非那定、富马酸非唑拉明、非西他滨、非阿尿苷、纤维蛋白质1 125、非格司亭、非律平、马来酸黄酮地洛、flavopiridol、黄酮哌酯盐酸、夫拉扎酮、氟卡尼、氟丁特罗、氟罗沙星、氟辛克生、硫酸氟司洛尔、氟乙西泮、氟卓斯汀、flobufen、夫洛非宁、氟地平、氟司喹南、氟氯西林、氟尿苷、fluasterone、氟扎可特、盐酸氟巴尼酯、氟苯咪唑、氟西吲哚、氟西吲哚、氟康唑、氟胞嘧啶、氟氘丙氨酸、磷酸氟达拉滨、氯氟哒唑、氟代脱氧葡萄糖F18、氟多雷司、醋酸氟氢可的松、氟芬那酸、氟苯柳、氟马西尼、氟甲喹、氟美立酮、氟米松、氟美吗酮、氟甲氮平、氟氨雷司、氟咪唑、氟莫奈德、氟硝唑、氟尼缩松、氟硝西泮、氟尼辛、fluocalcitriol、氟轻松丙酮、醋酸氟轻松、氟考丁酯、氟可龙、荧光素、盐酸fluorodaunorunicin、氟多巴F18、氟米龙、尿嘧啶、盐酸氟曲辛、氟西汀、盐酸氟西汀、氟甲睾酮、氟哌醇胺、醋酸氟培龙、癸酸氟奋乃静、氟泼尼龙、氟丙喹宗、氟前列醇钠、氟喹宗、盐酸氟朵林、氟羟可舒松、盐酸氟西泮、氟比洛芬、氟瑞托芬、氟西他滨、氟法胺、醋酸氟孕酮、三氟乙醚、氟乙烯醚、氟司哌隆、氟司必林、氟替卡松、丙酸氟替卡松、氟曲林、氟伐他汀、氟伐他汀钠、氟齐胺、叶酸、卵泡调节蛋白、制卵泡素、促卵泡激素α、促卵泡激素β、甲吡唑、甲磺酸二甲替嗪、福拉沙坦、福酚美克、forfenirmex、福美司坦、福莫可他、福莫特罗、磷利酯、膦西泮、膦甲酸钠、磷霉素、膦乙酸钠、福辛普利、福辛普利钠、福辛普利拉、磷苯妥英、磷喹酮、福司地尔、福司曲星、福莫司汀、品红、呋莫西林、真菌霉素、呋喃洛芬、痢特灵、呋唑氯铵、呋格雷酸钠、呋罗布芬、呋罗达唑、呋塞米、夫西地酸钠、夫西地酸、加巴喷丁、钆贝酸二葡甲胺、钆贝酸、钆布醇、钆双胺、钆texaphyrin、马根维显溶液Dimegiumine、钆特酸、钆特醇、钆弗塞胺、加兰他敏、加丹司琼、盐酸加丹司琼、戈拉碘铵、硝酸镓、戈洛帕米、加洛他滨、更非辛、加莫烯酸、更昔洛韦、加尼瑞克、四甲癸二醇、吉西他滨、吉美前列素、吉非罗齐、硫酸庆大霉素、龙胆紫、吉哌隆、孕氯酮、孕二烯酮、己酸孕诺酮、孕三烯酮、盐酸吉伏曲林、吉立索泮、甘精胰岛素、格拉莫德、格拉默、glaucocalyxinA、格来色林、格列胺脲、格列波脲、格列他尼钠、格列氟胺、格列美脲、格列吡嗪、格洛莫南、胰高血糖素、glutapyrone、格鲁米特、优降糖、glycopine、glycopril、格隆溴铵、格列己脲、格列嘧啶钠、格列辛脲、格列帕脲、Gold Au 198、Gonadoctrinins、戈那瑞林、促性腺激素、戈舍瑞林、短杆菌肽、格拉司琼、格帕沙星、灰黄霉素、愈创哌特、愈创茶碱、胍那苄、醋酸胍那苄、硫酸胍那决尔、胍西定、单硫酸胍乙啶、盐酸胍法辛、硫酸胍异喹、硫酸胍氯酚、盐酸胍诺克汀、胍诺沙苄、硫酸胍生、硫酸胍诺西芬、三盐酸胍立莫司、哈拉西泮、哈西奈德、halichondrin B,丙酸Halobetasol、氯氟菲醇、盐酸氯氟菲醇、降脂酰胺、氢溴酸溴氯哌喹酮、halomon/卤培米特、氟哌啶醇、卤泼尼松、卤孕酮、卤普罗近、氟烷、哈喹诺、哈霉素、hatomamicin、hatomarubigin A、hatomarubigin B、hatomarubigin C、hatomarubigin D、肝素钠、亥普舒芬(hepsulfam)、调节蛋白、海他西林、海特溴铵、六氯酚:过氧化氢、溴化己芴胺、亚甲基二乙酰胺、海克西定、海索苯定、硫酸海索那林、己雷琐辛、磷酸组胺、组氨酸、组胞浆菌素、组氨瑞林、醋酸组氨瑞林、氢溴酸后马托品、盐酸胡喹嗪、人绒毛膜促性腺激素、人生长激素、海恩酮、盐酸胼屈嗪、胼屈嗪Polistirex、氢氯噻嗪、氢酒石酸、氢化可的松、氢氟噻嗪、盐酸氢吗啡酮、氢溴酸羟基苯丙胺、硫酸羟氯喹、奥芬氨酯、羟己酸、羟基脲、盐酸羟、羟甲香豆素、莨菪碱、金丝桃素、依巴沙星、伊班膦酸钠、伊菠加因、异波帕胺、异丁司特、异丁芬酸、布洛芬、富马酸伊布利特、艾替班特醋酸、鱼石脂、艾可替定、去甲氧柔红霉素、艾多昔芬、疱疹净、伊决孟酮、伊非曲班、异环磷酰胺、Ilepeimide、illimaquinone、伊莫福新、伊洛马司他、伊洛达普、伊潘立酮、伊洛前列素、盐酸苯双咪唑、伊马替尼、盐酸伊马唑旦、咪达普利、imidazenil、imidazoacridone、咪癸碘、盐酸双咪苯脲、盐酸咪多林、咪脲、伊米苷酶、盐酸咪洛克生、亚胺培南、盐酸丙咪嗪、咪喹莫特、盐酸英普咪定、茚达立酮、吲达帕胺、盐酸英地卡尼、盐酸茚洛秦、靛胭脂钠、茚地那韦、硫酸茚地那韦、吲哚菁绿、盐酸吲哚普利、吲哚利旦、消炎痛、吲哚美辛钠、吲哚洛芬、吲哚拉明、盐酸吲哚瑞酯、吲哚克索、盐酸茚屈林、英夫利昔单抗、伊诺特隆、伊诺加群、伊诺莫单抗、肌醇烟酸酯、胰岛素、干扰素、白介素、吲四唑、盐酸英曲替林、碘苄胍、碘苯扎酸、碘比醇、碘卡明葡胺(IocarmateMeglumine)、双碘酞酸、碘西他酸、碘达胺、碘、胆影葡胺、碘克沙醇、iodoamiloride、碘安替比林I 131、碘胆甾醇I 131、碘阿霉素、碘马尿酸钠I 131、碘吡啦哈I 125、双碘喹啉、葡胺碘氧、Iodoxamie Acid、碘格利酸、盐酸碘非他胺I 123、碘拉醇、碘葡醇、碘葡胺、碘甘卡酸、Iogulamide、碘海醇、碘美普尔、Iomethin I 125、碘帕醇、碘番酸、碘喷托、碘苯酯、碘普西酸、碘普罗胺、碘普罗酸、碘吡多、碘吡酮、iopyrol、碘西法酸、碘丝酸、碘砜葡胺、碘琥酸、碘酞硫、碘替酸、碘酞钠、碘他拉酸、碘赛特、碘曲伦、碘曲西酸、Iotyrosine I 131、碘佛醇、碘克酸钠、碘克沙酸葡胺、碘克沙酸、碘昔兰、羟泛影酸、依帕利特、伊培沙宗、伊匹达克林、碘泊酸钙、甘薯苦醇、4-、异丙托溴铵、依普黄酮、伊普吲哚、Iprofenin、异丙硝唑、异丙铂、盐酸异丙沙明、伊沙匹隆、厄贝沙坦、依立替康、伊洛沙星、伊罗普拉、伊索拉定、伊替马唑、伊沙司坦、依沙莫可苏、伊波格雷、异帕米星、isobengazole、氨苯异丁酯、异卡波胼、异康唑、新异丙肾上腺素、isofloxythepin、醋酸异氟泼尼龙、异氟醚、异氟磷、isohomohalicondrinB、异亮氨酸、盐酸伊索马唑、盐酸异戊拉明、异烟胼、异丙胺碘、异丙醇、异丙基乌诺前列酮、盐酸异丙肾上腺素、异山梨醇、单硝酸异山梨酯、依索喹胺、异维A酸、伊索克酸、伊索昔康、盐酸异克舒令、伊拉地平、伊他美林、伊他司琼、伊他格雷、伊托必利、伊曲康唑、伊维菌素、jasplakinolide、交沙霉素、kahalalide F、卡拉芬净、硫酸卡那霉素、氯氨酮、酮色林、酮佐辛、凯他唑仑、乙氧丁酮醛、富马酸氧丙咪嗪、酮康唑、酮基布洛芬、酮啡诺、酮咯酸、富马酸酮替芬、吉他霉素、盐酸拉贝洛尔、拉西地平、拉西地平、乳糖醇、拉替维辛、乳糖酸、莱乃康、拉呋替丁、lamellarin-N三乙酸盐、拉米非班、拉米夫定、拉莫三嗪、拉诺康唑、地高辛、兰吡立松、兰瑞肽、兰瑞肽醋酸、兰索拉唑、拉帕替尼、拉罗匹仑、拉坦前列素、lateritin、鲁拉西酮、月桂氮酮、溴化十二烷基异喹啉、琥珀酸拉伏替丁、拉扎贝胺、来西贝特、leinamycin、来米地平、莱敏拉唑、来那西普、来尼喹新、来格司亭、仑哌隆、香菇多糖硫酸、来普汀、leptolstatin、乐卡地平、麦角腈、来立司琼、盐酸来替米特、来曲珠利、来曲唑、亮氨酸、leucomyzin、亮丙瑞林、醋酸亮丙瑞林、亮丙瑞林、左旋沙丁胺醇、琥珀酸左苯丙胺、左旋咪唑、乳糖酸左多巴酚丁胺、Leveromakalim、左乙拉西坦、Leveycloserine、左倍他洛尔、左布诺洛尔、左布比卡因、左卡巴斯汀、左卡尼汀、左西替利嗪、二盐酸左西替利嗪、左旋多巴、左羟丙哌嗪、左氧氟沙星、左呋喃他酮、左亚叶酸钙、醋酸左旋乙酰美沙酮、盐酸醋酸左旋乙酰美沙酮、左莫普洛尔、盐酸左南曲朵、左旋异肾上腺素、左炔诺孕酮、左丙氧芬、左普匹西林钾、左美洛昔芬、酒石酸左啡诺、左西孟旦、左旋舒必利、左旋甲状腺素、左甲状腺素钠、盐酸左沙屈尔、来昔帕泛、来红霉素、利阿唑、赖苯普利、盐酸利达脒、利多卡因、利多苯宁、利多氟嗪、利法利嗪、利贝特、利非贝罗、林那罗汀、林可霉素、线性多胺类似物、利诺格列、利诺吡啶、利诺曲班、林西多明、林替曲特、林托必利、碘塞罗宁1 125、碘甲腺氨酸钠、复方甲状腺素、利沙必利、利右苯丙胺二甲磺酸、赖诺普利、lissoclinamide 7、LixazinoneSulfate、洛铂、Lobenzarit Sodium、洛布卡韦、氯德拉苯、洛度沙胺、盐酸洛非咪唑、草酸洛芬太尼、盐酸洛非帕明、盐酸洛非西定、蚯蚓磷脂、洛美沙星、洛美利嗪、盐酸氯甲萘满满、洛美曲索、洛蒙霉素、Lomoxicam、洛莫司汀、氯萘帕林、氯那唑酸、氯尼达明、盐酸洛哌丁胺、氯碳头孢、盐酸缓脉灵氯乙酯、氯雷他定、劳拉西泮、劳氨酯、盐酸劳卡胺、氯瑞唑、Loreinadol、氯戊米特、氯甲西泮、氯诺昔康、氯诺昔康、氯他拉明、洛查酮、氯沙坦、氯西加酮、洛索蒽醌、盐酸洛硫嗪、氯替泼诺、洛伐他汀、洛韦胺、洛沙平、洛索立宾、芦贝鲁唑、盐酸硫蒽酮、鲁非罗尼、甲磺酸卢罗司琼、勒托替康、促黄体激素、鲁拉西酮、镥、醋酸黄体瑞林、褪黑素受体拮抗剂(luzindole)、阿朴酸钠、氨棕己胺、利地霉素、利迪霉素、利奈孕酮、赖氨加压素、赖氨酸、lysofylline、溶葡球菌酶、裂解肽、马杜霉素、磺胺米隆、蛙皮素2酰胺、水杨酸镁、硫酸镁、厚朴酚、美坦新、聚马来乙烯、野梧桐色原烯、mallotojaponin、马洛替酯、马洛替酯、锰福地吡、马尼地平、maniwamycin A、甘露醇、mannostatin A、手霉素E、手霉素F、马哌斯汀、马普替林、马拉韦罗、马立马司他、屈大麻酚、马索罗酚、maspin,massetolide,美登素、琥珀酸马扎哌汀、马吲哚、甲苯咪唑、盐酸美贝维林、甲溴菲宁、美布氨酯、盐酸美加明、盐酸氮芥、盐酸美克洛嗪、甲氯环素、甲氯灭酸钠、甲氯喹酮、二丁酸甲氯松、盐酸美达西泮、美多力农、美屈孕酮、美沙洛尔、甲孕酮、甲羟松、盐酸美克洛嗪、甲灭酸、甲苯地尔、盐酸美芬雷司、美非沙胺、盐酸甲氟喹、美夫西特、巨霉素磷酸二氢钾、醋酸甲地孕酮、葡甲胺、美格鲁托、甲烯雌醇乙酸酯、美洛昔康、美法仑、美金刚、盐酸美莫汀、盐酸美大麻坦、美诺克酮、美诺立尔、促生育素、硫酸甲氧苯汀、美帕曲星、溴美喷酯铵、盐酸哌替啶、硫酸美芬丁胺、美芬妥英、甲苯比妥、盐酸甲哌卡因、安宁片、盐酸美普他酚、美喹多司、汞林钠、merbarone、巯嘌呤、氯酚汞、与氨化合的汞、放射性汞丙醇Hg 197、美罗培南、美沙拉嗪、美西拉宗、美索达嗪、美睾酮、美雌醇、盐酸美舒令、盐酸美他洛尔、奥西那林烯复合物、酒石酸间羟胺、美他沙酮、甲烯前列素、美替瑞林、二甲双胍、氯醋甲胆碱、甲烯土霉素、美沙酮、醋美沙朵、美沙噻嗪、盐酸去氧麻黄碱、甲喹酮、醋甲唑、甲地嗪、乌洛托品、醋酸美替诺龙、美替妥英、甲氧苯青霉素钠、他巴唑、蛋氨酸酶、蛋氨酸、甲吲噻踪、盐酸甲哌噻吨、美索巴莫、美索比妥钠、甲氧夫啉、甲氨蝶呤、左美丙嗪、methoxatone、巯嘌呤、甲氧基聚乙二醇-促红细胞生成素β、甲氧氟烷、甲琥胺、甲氯噻嗪、帕莫酸甲酯、硝甲阿托品、甲苄索氯铵、甲基多巴、盐酸甲基多巴、亚甲基蓝、马来酸甲基麦角新碱、甲基组胺、一磷酸甲基肌苷、哌甲酯、甲基强的松龙、甲睾酮、Methynodiol Diacelate、美西麦角、马来酸美西麦角、甲硫米特、甲硫平、美替普林、metipamide、美替洛尔、盐酸美替唑啉、醋酸美克法胺、胃复安、碘二甲箭毒、美托孕素、美托拉宗、美托哌丙嗪、氯苯氨啶、美托洛尔、美托喹嗪、美曲磷酯、甲泛葡胺、甲泛影钠、甲硝唑、美妥替哌、美替拉酮、甲酪氨酸、盐酸美西律、孕甲酯丙酸钾、美洛西林、盐酸米安色林、米贝拉地尔、二盐酸米贝拉地尔、米勃酮、michellamine B、达克宁、microcolin A、咪达氟、盐酸咪达唑仑、米多君、米非司酮、米福酯、米格列醇、米拉醋胺、米拉美林、米屈胼、咪仑哌隆、米利哌汀、米那普仑、米力农、米替福新、盐酸米姆本、米那普令、米那索龙、米诺罗米、米诺环素、米诺环素、盐酸米诺地尔、盐酸米氟嗅、米卡霉素、米普拉苷、米芬太尼、米立司亭、盐酸米林霉素、马来酸米立司琼、米氮平、米索硝唑、米索前列醇、米丁度胺、米托克星、丝裂红素、米托洁林、米托胍腙、二溴卫矛醇、米托马星、丝裂霉素、米托萘胺、米托司培、米托坦、米托蒽醌、米库氯铵、米伐折醇、mixanpril、米克昔定、咪唑斯汀、咪唑立宾、吗氯贝胺、莫达非尼、硫酸莫达林、莫地卡尼、莫昔普利、莫法罗汀、盐酸莫非吉兰、莫苯唑酸、莫拉司亭、吗林那宗、盐酸吗茚酮、吗多明、糠酸、马来酸莫那匹尔、莫能菌素、甘油辛酸酯和甘油癸酸酯混合物、孟鲁司特、孟鲁司特钠、孟替瑞林、莫哌达醇、莫雷西嗪、酒石酸莫仑太尔、莫雷西嗪、吗尼氟酯、吗啡、鱼肝油酸钠、莫沙帕明、莫沙比利、motilide、莫维A胺、拉氧头孢二钠、莫沙佐辛、莫西沙星、莫昔普令、吗硝唑、莫索尼定、流行性腮腺炎皮试抗原、莫唑胺、mycaperoxide B、霉酚酸酯、霉酚酸、myriaporone、大麻折尼、大麻隆、盐酸大麻坦、盐酸大麻克酯、萘丁美酮、N-acetyldinaline、Nadide、那氟沙星、纳多洛尔、那屈肝素钙、那法道曲、萘莫司他、那法瑞林、萘夫西林钠、萘酚平、盐酸萘咪酮、萘非可特、苹果酸萘甲羟胺、盐酸萘福昔定、草酸萘呋胺酯、盐酸萘替芬、萘哌地尔、那格列钒、nagrestip、盐酸纳布啡、Nalidixate Sodium、萘啶酸、纳美芬、盐酸纳美酮、纳洛酮、纳曲酮、纳莫雷特、苯丙酸诺龙、盐酸南曲朵、盐酸萘帕他定、萘二磺酸盐、盐酸奈帕咪唑、napaviin、盐酸萘甲唑啉、naphterpin、萘普生、萘普生钠、萘普索、奈沙加群、盐酸萘拉诺、甲基盐霉素、那拉曲坦、那托司亭、那沙普酶、那他珠单抗、纳他霉素、那替普酶、盐酸那高利特、奈必洛尔、尼拉霉素、奈达钼、奈多罗米、盐酸奈法唑酮、盐酸奈氟齐特、盐酸奈福泮、马来酸奈来扎林、盐酸奈马唑啉、奈莫柔比星、棕榈酸新霉素、新斯的明溴、奈立膦酸、硫酸奈替米星、中性霉素、Neyirapin、盐酸奈西利定、烟酸、硝溴生、盐酸尼卡地平、尼麦角林、氯硝柳胺、尼可地尔、烟酰胺、烟醇、硝苯地平、Nifirmerone、尼氟利地、硝呋拉定、硝呋地腙、硝呋太尔、硝呋隆、硝呋达齐、硝呋米特、硝呋吡醇、硝呋奎唑、硝呋噻唑、硝呋替莫、尼罗替尼、一水合盐酸尼罗替尼、尼鲁米特、尼伐地平、尼马宗、尼莫地平、尼培替丁、尼拉伏林、尼立达唑、nisamycin、甲磺酸尼司特罗、乳酸链球菌素、尼索氨酯、尼索地平、尼索西汀、雄硝肟醋酯、硝苯胂酸、硝唑尼特、硝替卡朋、盐酸硝呋坦、盐酸硝拉明、盐酸硝拉咪唑、硝西泮、尼群地平、Nitrocydine、硝旦、呋喃妥因、呋喃西林、硝酸甘油、硝甲酚汞、硝米特、柠檬酸硝米芬、氧化亚氮、一氧化二氮抗氧化剂、nitrullyn、尼伐可醇、双甲硝茚酮钠、尼扎替丁、诺柏斯汀、噻氨酯哒唑、诺拉霉素、诺利溴铵、马来酸诺米芬辛、盐酸诺美沙朵、二乙诺酮、酒石酸去甲肾上腺素、炔诺酮、异炔诺酮、Norfiurane、诺氟沙星、诺孕酯、诺孕美特、炔诺孕酮、盐酸去甲替林、那可丁、尼尔雌醇新生霉素、制霉菌素、双复磷、奥卡哌酮、盐酸奥芬太尼、奥西普隆、辛酸、奥他酰胺、盐酸奥替尼啶、奥托君、奥曲肽、磷酸奥克替林、氟嗪酸、奥福宁、okicenone、奥氮平、寡核苷酸、奥洛他定、奥普力农、奥沙拉嗪、奥沙拉嗪钠、奥伐尼、奥美拉唑、奥那司酮、昂丹司琼、昂唑司特、卵母细胞成熟抑制因子、盐酸奥匹哌醇、oracin、硝酸奥康唑、奥古蛋白、Orlislat、奥马铂、奥美普林、奥硝唑、奥帕诺辛、柠檬酸奥芬那君、奥沙特隆、奥司他韦、奥腾折帕、苯唑西林钠、氧格雷酯、奥沙利铂、盐酸奥沙香豆素、奥沙米索、奥沙尼喹、氧雄龙、双羟萘酸奥克太尔、盐酸羟丙替林、奥沙普秦、奥沙巴唑、奥沙米特、oxaunomycin、奥沙西泮、奥卡西平、奥生多龙、乙氧连氮、富马酸奥昔托隆、奥芬达唑、羟苯甘氨酸、奥苯达唑、奥昔康唑、羟多巴胺、奥昔磷酸、盐酸奥昔芬净、奥昔啡烷、肟莫南、肟莫南钠、奥哌咪酮、奥拉西坦、奥昔拉米、奥昔舒仑、盐酸奥美替丁、奥索地平、苯丙酸奥索孕酮、奥索利酸、盐酸氧烯洛尔、胆茶碱、氯化奥昔布宁、奥昔氯生、羟考酮、羟考酮盐酸盐、盐酸羟甲唑啉、羟甲烯龙、盐酸羟吗啡酮、奥昔哌汀、羟布宗、别嘌呤二醇、土霉素、催产素、奥扎格雷、奥唑林酮、紫杉醇、palauamine、帕地霉素、帕利那韦、帕利珠单抗、palmitoylrhizoxin、帕莫酸钠、帕马苷、硫酸帕马洛尔、帕米格雷、帕米膦酸二钠、帕米磷酸、帕那普隆、帕那美新、人参炔三醇、泮考必利、泮库溴铵、帕尼培南、pannorin、帕诺米芬、泛硫乙胺、泮托拉唑、盐酸罂粟碱、parabactin、对氯酚、三聚乙醛、醋酸帕拉米松、盐酸瑞尼托林、溴帕拉喷酯、双羟萘酸副品红、帕苯达唑、盐酸帕康唑、复方樟脑酊、硫酸帕立太特、盐酸帕吉林、帕肝素钠、硫酸巴龙霉素、帕罗西汀、盐酸帕罗西汀、小白菊内酯、帕曲星、保洛霉素、帕折普汀、帕秦克隆、帕佐昔特、帕珠沙星、培氟沙星、培门冬酶、培戈汀、盐酸培兰色林、培得星、佩里霉素、培维A、盐酸培力农、培美酸、硝酸哌美立特、培美曲塞、吡嘧司特、匹莫林、培那西林、硫酸喷布洛尔、喷昔洛韦、五氟利多、青霉胺、苄星青霉素G、青霉素G钾、普鲁卡因青霉素G、青霉素G钠、青霉素V、苄星青霉素V、海巴明青霉素V、青霉素V钾、喷他氨酯、季戊四醇四硝酸酯、喷他夫西、喷他脒、戊吗酮、溴新斯的明、甲硫戊哌铵、喷他佐辛、三胺五乙酸、马来酸喷硫平、喷替吉肽、喷替米星、戊胺唑酮钠、戊巴比妥、喷托孟、喷托普利、戊聚糖、喷司他丁、己酮可可碱、戊硝醇、pentrozole、硫酸培洛霉素、胃酶抑素、全氟溴烷、perfofamide、培磷酰胺、培高利特、马来酸哌克昔林、紫苏醇、培哚普利、培哚普利拉、Perlapine、Permethrin、哌罗匹隆、奋乃静、苯乙酰脲、phenaridine、phenazinomycin、盐酸那吡啶、甘油保泰松钠、芬卡米特、盐酸苯环己哌啶、酒石酸苯甲曲秦、硫酸苯乙胼、苯乙双胍、盐酸芬美曲秦、苯巴比妥、盐酸酚苄明、苯丙香豆素、phenserine、phensuccinal、苯琥胺、芬特明、盐酸芬特明、甲磺酸酚妥拉明、Phentoxifylline、苯基氨基水杨酸、苯乙酸、苯丙氨酸、phenylalanyl ketoconazole、保泰松、盐酸去氧肾上腺素、盐酸苯丙醇胺、苯丙醇胺Polistirex、盐酸非尼拉朵、苯妥英、苯妥英纳、毒扁豆碱、甲丙哌酚、毕西巴尼、二乙醇胺匹考群、胡黄连活素、吡库特罗、匹多莫德、哌法宁、毛果芸香碱、吡西卡尼、匹马吉定、盐酸匹美汀、匹米前列素、匹莫苯、匹莫齐特、吡那地尔、匹那朵林、吲哚洛尔、pinnenol、pinocebrin、盐酸哌氧平、吡格列酮、匹泮哌隆、匹哌氮酯、哌库溴铵、哌西他嗪、哌拉西林钠、马来酸哌拉酰胺、哌嗪、哌泊溴烷、哌泊舒凡、棕榈酸哌泊噻嗪、盐酸哌泊索仑、哌普唑林、盐酸匹喹酮、哌喹齐尔、盐酸哌喹齐尔、吡拉西坦、盐酸吡喃达明、吡柔比星、吡拉莫南钠、吡拉唑酸、吡苄西林钠、醋酸吡布特罗、匹仑哌隆、盐酸哌仑西平、吡咯他尼、吡非尼酮、吡地西林钠、Piridronate钠、吡前列素、吡曲克辛、盐酸吡利霉素、吡吲哚、吡吗格雷、盐酸吡美诺、四甲苯喃酯、羟甲辛吡酮、吡罗达韦、吡咯司特、酒石酸吡咯格列、匹罗酯、吡拉酰胺、P盐酸吡罗蒽醌、吡罗昔康、匹罗昔酮、吡洛芬、吡喹诺唑、哌多明、盐酸匹氨西林、匹伏普利、苯噻啶、placetin A、普卡霉素、普洛美坦、泊比司特乙二胺、普达非洛、太平洋漆树提取物、甲硫酸波尔定、聚氨葡糖、Polignate钠、硫酸多粘菌素B、泊利噻嗪、泊那司他、卟菲尔钠、泊非霉素、氯化钾、碘化钾、高锰酸钾、聚维酮碘、普拉洛尔、氯磷定、普拉克索、盐酸普拉西坦、盐酸丙吗卡因、氯解磷定、马来酸普拉朵林、普伐他汀、普伐他汀钠、普拉西泮、哌唑嗪、盐酸哌唑嗪、泼那扎特、泼尼卡酯、泼尼莫司汀、强的松、强的松龙、富马酸奎硫平、强的松、强的松龙戊酸酯、普瑞巴林、琥珀酸孕烯醇酮、盐酸普瑞特罗、普尼拉明、盐酸普地利定、普罗度酸、盐酸普罗法朵、普罗加胺、盐酸普立地芬、普立非酮、盐酸丙胺卡因、奥美拉唑、磷酸伯氨喹、普米洛尔、扑米酮、赖诺普利、普林米特氨丁三醇、普啉索旦、pritosufloxacin、盐酸普齐地洛、盐酸普罗地芬、丙磺舒、普克罗米钙、普罗布考、盐酸普鲁卡因胺、盐酸普鲁卡因、盐酸甲基苄胼、盐酸丙卡特罗、丙氯拉嗪、普西奈德、丙氯诺、盐酸丙环定、盐酸普地利定、普罗度酸、盐酸普罗法朵、卤加比、黄体酮、丙谷胺、胰岛素原(人)、脯氨酸、盐酸普罗林坦、盐酸丙嗪、异丙嗪、盐酸异丙嗪、盐酸普罗帕酮、丙帕锗、丙泮尼地、溴丙胺太林、盐酸丙美卡因、硝酸Propatyl、丙戊茶碱、盐酸环苯哌酯、普匹卡星、丙酰马嗪、丙酸、propionylcarnitine、L-、丙吡兰、丙吡兰+扑热息痛、丙哌维林、异丙酚、盐酸Proponolol、盐酸丙氧卡因、盐酸丙氧芬、盐酸普萘洛尔、西沙必利、丙基双吖啶酮、丙己君、丙碘酮、丙基硫氧嘧啶、普罗喹宗、丙利酸钾、盐酸普罗克生、海葱次苷、前列他林、prostratin、硫酸鱼精蛋白、内源性抗微生物多肽、普罗瑞林、盐酸普罗替林、普罗沙唑、柠檬酸普罗沙唑、普昔罗米、酒石酸普罗啡烷、普卢利沙星、伪麻黄碱、盐酸伪麻黄碱、嘌呤霉素、吡拉布隆、双羟萘酸噻嘧唳、吡嗪酰胺、吡唑霉素、吡唑啉吖啶、吡啶斯的明、盐酸吡哆醇、甲氧苄二胺马来酸、乙胺嘧啶、吡诺林、吡硫钠、吡硫锌、盐酸吡咯戊酮、马来酸吡咯沙敏、吡咯卡因、盐酸吡咯苯丙酯、吡咯尼群、扑蛲灵、甲磺酸夸达佐辛、夸西泮、喹齐酮、夸唑定、喹唑司特、喹硫平、富马酸喹硫平、喹夫拉朋、喹高利特、喹那定蓝、喹那普利、盐酸喹那普利、盐酸喹唑嗪、奎勃龙、Quinctolate、醋酸喹地卡明、喹度溴铵、盐酸喹洛雷、炔雌醚、喹法米特、醋酸奎孕醇、葡萄糖酸奎孕酮、盐酸Quinielorane、硫酸奎宁、盐酸喹吡罗、硫酸喹丙那林、奎纽溴铵、奎奴普丁、马来酸喹哌嗪、雷贝拉唑、雷贝拉唑钠、消旋甲砜霉素、消旋肾上腺素、雷复尼特、雷利托林、雷洛昔芬、拉替拉韦、雷替曲塞、雷马曲班、雷米普利、雷莫拉宁、雷莫司琼、雷奈酸、雷尼霉素、雷尼替丁、盐酸雷尼替丁、雷诺嗪、萝芙木蛇根碱、瑞卡南、盐酸瑞卡南、瑞氯西泮、重组VIII因子、瑞加韦单抗、瑞拉司亭、松弛素、瑞洛霉素、盐酸瑞马西胺、盐酸瑞芬太尼、瑞前列醇、瑞莫必利、瑞吡司特、瑞普米星、盐酸瑞普特罗、利血平、resinferatoxin、间苯二酚、瑞他莫林、去甲基化瑞替普汀、reticulon、瑞维肝素钠、瑞维齐农、铼依替膦酸钠、根霉素、RII retinamide、利巴米诺、利巴韦林、利波腺苷、利卡司琼、利多格雷、利福布汀、利福美坦、利福克昔、利福米特、利福平、利福喷丁、利福昔明、利洛吡司、利鲁唑、金刚乙胺、盐酸林卡唑、利美索龙、氢溴酸利米特罗、利莫那班、利莫罗近、利奥地平、利奥前列素、利帕西泮、利匹沙坦、利塞膦酸钠、利塞膦酸钠、利塞膦酸、利索卡因、盐酸利索利特、利喷西平、利培酮、利培酮、利坦色林、利替培南、利托君、利托司特、利托那韦、美罗华、卡巴拉汀、酒石酸卡巴拉汀、利扎曲普坦、苯甲酸利扎曲普坦、盐酸罗卡斯汀、罗库溴铵、罗多卡因、罗氟烷、罗谷亚胺、rohitukine、罗他霉素、Roletamicide、罗加米定、罗利普令、咯利普兰、罗利环素、罗咯定、氯马扎利、罗莫肽、罗硝唑、罗匹尼罗、盐酸罗匹妥英、罗哌卡因、罗匹嗪、罗喹美克、罗沙米星、罗格列酮、马来酸罗格列酮、罗索沙星、瑞舒伐他汀、轮状病毒疫苗、罗替戈汀、罗托沙敏、roxaitidine、洛克沙生、罗克吲哚、罗红霉素、rubiginone B1、ruboxyl、芦氟沙星、rupatidine、芦他霉素、卢扎朵仑、沙贝鲁唑、沙芬戈、沙非罗尼、saintopin、沙丁胺醇、硫酸沙丁胺醇、柳胆来司、马来酸二乙氨乙柳胺、水杨醇、水杨酰胺、水杨酸葡甲胺、水杨酸、沙美特罗、沙那西定、双水杨酯、沙美利定、山帕曲拉、山环素、山费培南、血根氯铵、沙康唑、普立沙坦、沙丙蝶呤、盐酸沙丙蝶呤、沙奎那韦、盐酸沙拉沙星、沙丙蝶呤、肌植醇A、沙格司亭、沙莫西林、沙匹西林、沙格雷酯、沙芦普酶、沙特力农、沙替格雷、沙妥莫单抗喷地肽、司可芬净、氢溴酸东茛菪碱、盐酸Scrazaipine、司骨化醇、司可巴比妥、Seelzone、醋酸司格列肽、selegiline、盐酸司来吉兰、硫化硒、硒代蛋氨酸硒-75、塞福太、司美利特、生度米星、司莫地尔、司莫司汀、氯化三苯唑、盐酸氯氟哌醇、司普立糖、盐酸塞罗西汀、醋酸丝拉克肽、马来酸麦角克索、丝氨酸、丝美辛、醋酸舍莫瑞林、舍他康唑、舍吲哚、舍曲林、司普替林、司托哌隆、司维拉姆、司韦单抗、七氟醚、司佐胺、西波吡啶、盐酸西布曲明、信号转导抑制剂、硅雄酮、silipide、西替普酶、硝酸银、西孟旦、辛曲秦、辛伐他汀、辛卡利特、西奈芬净、西硝地尔、sinnabidol、西帕曲近、雷帕霉素、西索米星、西他列汀、西托糖苷、西佐喃、索布佐生、硝普钠、碘化钠1-123、硝普钠、羟丁酸钠、苯乙酸钠、水杨酸钠、丙戊酸钠、索非那、solverol、酒石酸索立哌汀、猪丙氨生长素、盐酸索金刚胺、生长调节素B、生长调节素C、生长抑素、人蛋氨生长素、生长激素、猪诺生长素、牛度生长素、索比尼尔、索立夫定、索他洛尔、盐酸索特瑞醇、司帕沙星、磷乙酰天冬氨酸钠、膦门冬酸、司帕霉素、硫酸司巴丁、盐酸大观霉素、spicamycin D、螺哌隆、甲磺酸螺朵林、螺旋霉素、盐酸螺普利、螺普利拉、盐酸锗螺胺、螺莫司汀、安体舒通、螺钼、螺沙宗、splenopentin、spongistatin 1、镝双胺、角鲨胺、盐酸司他霉素、焦磷酸亚锡、锡硫胶体、康力龙、匍枝青霉菌素、星形孢菌素、司他夫定、司替霉素、醋酸司腾勃龙、司替罗宁、司替碘铵、司洛碘铵、stipiamide、司替戊醇、stobadine、硫酸链霉素、链霉素异烟胼、链黑菌素、链脲霉素、氯化锶Sr-89、succibun、二巯丁二酸、氯化琥珀胆碱、硫糖铝、硫糖酯钾、舒多昔康、舒芬太尼、舒福替丁、硫西泮、舒巴坦酯、硝酸硫康唑、磺胺苯、磺胺苯酰、磺胺醋酰、磺胺乙胞嘧啶、磺胺嘧啶、磺胺多辛、磺胺林、磺胺甲基嘧啶、磺胺对甲氧嘧啶、磺胺二甲嘧啶、磺胺甲二唑、磺胺甲基异噁唑、磺胺间甲氧嘧啶、磺胺噁唑、磺胺酸锌、磺胺硝苯、柳氮磺胺吡啶、磺胺异噻唑、磺胺吡唑、盐酸硫氧洛尔、sulfinosine、磺吡酮、磺胺异噁唑、磺粘菌素、磺粘菌素、盐酸磺酰特罗、sulfoxamine、Sulinldac、硫马林、舒硝唑、舒洛地尔、磺氯苯脲、硫培南、草酸舒洛昔芬、舒必利、硫前列酮、舒他西林、舒噻美、舒托必利、硫鲁司特、舒马罗汀、舒马普坦、琥珀酸舒马普坦、森西林钠、舒普罗酮、舒洛芬、suradista、苏拉明、舒福姆、马来酸舒立卡尼、舒立托唑、马来酸舒罗吖啶、硫酸琥甲哌酯、苦马豆素、symakalim、氯氧三嗪、盐酸昔美汀、盐酸Taciamine、盐酸他克林、他克莫司、他达拉非、盐酸酞氨西林、左环十四酮酚、他利霉素、他莫司汀、他美辛、他尼氟酯、盐酸他洛普仑、他洛柳酯、盐酸他美曲林、他莫昔芬、柠檬酸他莫昔芬、富马酸坦帕明、坦索罗辛、盐酸坦索罗辛、盐酸坦达明、坦度螺酮、tapgen、他前列烯、他索沙坦、牛碘莫司汀、紫杉烷、Taxoid、琥珀酸他扎朵林、他扎司特、他扎罗汀、他齐茶碱、盐酸他齐茶碱、他唑巴坦、他唑非隆、盐酸他佐洛尔、特丁非隆、替布喹、替克洛占、Tecogalan钠、Teecleukin、替氟烷、替加氟、替加色罗、卡马西平、替考拉宁、替仑西平、tellurapyrylium、替美司坦、替米沙坦、盐酸替洛蒽醌、盐酸替鲁地平、盐酸替马沙星、Tematropium Methyl sulfate、替马西泮、替美斯汀、替莫普利、替莫西林、替莫泊芬、替莫唑胺、坦西莫司、替尼达普、替尼泊苷、泰诺福韦、替诺柳、替诺昔康、替吡吲哚、替泊沙林、替普罗肽、特拉唑嗪、盐酸特拉唑嗪、特比萘芬、硫酸特布他林、特康唑、特非那定、terf 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B、加压素、维库溴铵、维拉雷琐、马来酸维吖啶、文拉法辛、盐酸万拉法新、盐酸维拉朵林、藜芦明、盐酸维拉帕米、verdins、盐酸维立洛泮、维鲁司特、维罗茶碱、veroxan、维替泊芬、维司力农、vexibinol、阿糖腺苷、氨己烯酸、维格列汀、盐酸维洛沙秦、硫酸长春碱、柠檬酸长春布宁、乙烯磷、长春考酯、硫酸长春新碱、长春地辛、长春地辛硫酸、硫酸长春匹定、硫酸长春甘酯、硫酸长春罗新、长春瑞滨、长春西汀、长春培醇、vinxaltine、硫酸长春利定、维前列醇、维吉尼亚、绿黄菌素、韦罗肟、vitaxin、伏格列波糖、伏拉佐辛、伏立康唑、伏氯唑、伏高利特、华法林钠、扎莫特罗、咕诺美林、异丙氧蒽酸钠、占替诺烟酸酯、珍米洛非班、联苯利平、联苯丁酸、希洛班、希莫洛芬、希帕胺、甲磺酸佐尔啡诺、对甲苯磺酸Xylamidine、盐酸甲苯噻嗪、盐酸赛洛唑啉、木糖、yangambin、扎比普利、扎考必利、扎鲁司特、扎西他滨、扎来普隆、扎螺酮、盐酸唑替丁、扎托洛芬、扎那米韦、占吉仑、扎诺特隆、扎特克、扎替雷定、扎替雷定、扎托司琼、马来酸扎托司琼、折那司他、甲磺酸泽来索兴、折尼钼、玉米赤霉醇、齐多夫定、齐罗硅酮、齐仑太尔、亚苄维c、齐留通、盐酸齐美定、十一烯酸锌、嗪多群、盐酸齐诺康唑、净司他丁、盐酸净特罗、净韦肟、齐拉西酮、Zobolt、佐芬普利钙、佐芬普利拉、盐酸佐拉敏、盐酸唑拉西泮、唑来膦酸盐、盐酸佐勒汀、佐米曲普坦、唑吡坦、佐美酸钠、氯苯吡卓、盐酸佐尼氯唑、唑尼沙胺、佐匹克隆、唑泊司他、佐尔博霉素、盐酸佐柔比星、佐替平、珠卡赛辛。
用于在本文中使用的另一种可接受的药物活性物质是芦玛哌酮(lumateperone)、如在美国专利号9745300、9708322、7183282、7071186、6552017、8648077、8598119、9751883、9371324、9315504、9428506、8993572、8309722、6713471、8779139、9168258、RE039680E1、9616061、9586960中和在美国专利公开号2017114037、2017183350、2015072964、2004034015、2017189398、2016310502、2015080404中所公开的、上述专利的内容以引用方式全文并入本文。
抗糖尿病活性物质的其他示例包括但不限于JTT-501(PNU-182716)(Reglitazar)、AR-H039242、MCC-555(Netoglitazone)、AR-H049020(Tesaglitazar)、CS-011(CI-1037)、GW-409544×、KRP-297、RG-12525、BM-15.2054、CLX-0940、CLX-0921、DRF-2189、GW-1929、GW-9820、LR-90、LY-510929、NIP-221、NIP-223、JTP-20993、LY 29311Na、FK614、BMS 298585、R 483、TAK 559、DRF 2725(Ragaglitazar)、L-686398、L-168049、L-805645、L-054852、去甲基甾烷二酮B1(Demethyl asteriquinone)(L-783281)、L-363586、KRP-297、P32/98、CRE-16336和EML-16257。
本发明的剂型中可包括多种药物、有生物活性的活性物质和药物组合物。有用药物的示例包括血管紧张素转化酶抑制剂、抗心绞痛药、抗心律失常药、抗哮喘剂、抗高胆固醇血症药、镇痛剂、麻醉剂、抗惊厥药、抗抑郁剂、抗糖尿病剂、抗腹泻制剂、解毒剂、抗组胺剂、抗高血压药、抗炎剂、抗脂质剂、抗躁狂剂、抗呕吐剂、抗中风剂、抗甲状腺制剂、抗肿瘤药、抗病毒剂、痤疮药、生物碱、氨基酸制剂、镇咳剂、抗高尿酸血症药、抗病毒药、合成代谢制剂、全身性和非全身性抗感染剂、抗赘瘤剂、抗帕金森症药剂、抗风湿剂、食欲刺激剂、生物反应调节剂、血液调节剂、骨代谢调控剂、心血管药剂、中枢神经系统刺激剂、胆碱酯酶抑制剂、避孕药、解充血剂、膳食补充剂、多巴胺受体激动剂、子宫内膜异位控制剂、勃起功能障碍治疗剂、致育剂、胃肠道药剂、顺势治疗剂、激素、高血钙症和低血钙症控制剂、免疫调节剂、免疫抑制剂、偏头痛制剂、运动病治疗剂、肌肉松弛剂、肥胖控制剂、骨质疏松制剂、催产素、副交感神经剂、拟副交感神经剂、前列腺素、心理治疗剂、呼吸道药剂、镇静剂、戒烟辅助剂、交感神经阻滞剂、震颤制剂、尿路药剂、血管扩张剂、轻泻剂、抗酸剂、离子交换树脂、退热剂、食欲抑制剂、祛痰剂、抗焦虑剂、抗溃疡剂、抗炎物质、冠状血管扩张剂、脑扩张剂、外周血管扩张剂、精神病药剂、剌激剂、抗高血压药、血管收缩剂、偏头痛治疗剂、抗生素、镇定剂、抗精神病剂、抗肿瘤药、抗凝血剂、抗血栓药、催眠药、止吐剂、抗恶心剂、抗惊厥剂、神经肌肉药、高血糖和低血糖药剂、甲状腺和抗甲状腺制剂、利尿剂、抗痉挛剂、子宫松弛药、抗肥胖药、促红细胞生成药、抗哮喘剂、咳嗽抑制剂、粘液溶解剂、DNA和遗传修饰药物、以及它们的组合。
控释剂型
术语“控释”旨在意谓以预选或期望的速率释放活性物质。该速率将取决于应用而变化。理想的速率包括快速释放或立即释放曲线以及延迟释放、缓释或顺序释放。考虑了释放模式的组合,诸如活性物质的初始尖峰释放之后是较低水平的缓释。还考虑了脉冲药品释放。
被选择用于本发明剂型的聚合物也可被选择以允许活性物质的崩解。这可通过提供基本上不溶于水的膜来实现,该膜结合了随着时间推移将从剂型释放的活性物质。这可通过掺入各种不同的可溶性或不溶性聚合物来实现、并且还可包含可生物降解的聚合物的组合。或者,可将包衣的控释活性物质颗粒掺入易溶的膜基质中,以在服用时实现活性物质在消化系统内部的控释特性。
提供活性物质的控释的膜对于经颊、牙龈、舌下和阴道应用特别有用。本发明的膜在存在粘膜或粘膜液的情况下特别有用,因为它们能够容易地润湿和粘附到这些区域。
长期以来,在制药领域已经认识到,与以规则的时间间隔施用多个单剂量相比,施用单一剂量药物的便利性在于其以受控方式在延长的时间段内释放活性成分。对于患者和临床医生来说在延长的时间段内具有一致和统一的药物血液水平的优点同样得到了认可。各种缓释剂型的优点是众所周知的。然而,制备提供活性物质的控释的膜剂除具有控释片剂众所周知的优点外,还具有其他优点。例如,由于薄膜不需要像片剂一样被吞咽,因此薄膜很难被无意间吸出并提供了提高的患者依从性。而且,本发明的膜的某些实施方案被设计成粘附到颊腔和舌头上,在颊腔和舌头上所述膜可控地溶解。此外,薄膜不可以控释片剂的方式压碎,这是导致药物(诸如奥施康定)滥用的问题。
可将本发明中采用的活性物质以控释形式掺入本发明的膜剂或其他剂型组合物中。例如,药品颗粒可用聚合物(诸如乙基纤维素或聚甲基丙烯酸酯)包被,该乙基纤维素或聚甲基丙烯酸酯分别可以商标名诸如Aquacoat ECD和Eudragit E-100商购获得。也可将药品溶液吸收到此类聚合物材料上,并掺入到本发明的膜组合物中。也可在这种控释组合物中使用其他组分,诸如脂肪和蜡、以及甜味剂和/或调味品。
如在标题为“基于聚合物的膜和由其制成的药物递送系统(Polymer Based Filmsand Drug Delivery Systems Made Therefrom)”的美国专利申请公开号2007/0281003中所述,在将活性物质掺入膜组合物中之前可对活性物质进行掩味,该美国专利申请公开以引用方式并入本文。在下文描述了如本文所公开的对活性物质进行掩味。
微粒状活性物质掩味
将本发明中采用的活性剂以经掩味的或控释的形式掺入本发明的膜组合物中。掩味可用于避免往往与活性剂(诸如药物)有关的令人不快的味道效应,诸如苦味。在该实施方案中,药品颗粒可用掩味剂包衣,所述掩味剂为例如聚合物、油或蜡。另外,感官剂,诸如但不限于甜味剂和/或调味品,也可用于此类经掩味的组合物中,包含在掩味剂的包衣层中。在替代的实施方案中,颗粒包衣赋予控释、延迟释放或缓释的特性,从而延迟了活性剂从消费者口腔或肠道中的颗粒的释放。
经掩味或控释的颗粒可为任何有用的感官剂、美容剂(cosmetic agent)、药剂,或它们的组合。有用的感官剂包括调味品和甜味剂。有用的美容剂包括口气清新剂或减充血剂,诸如薄荷醇,包括薄荷醇晶体。
标题为“用于掺入了掩味组合物的速溶剂型的均匀膜(Uniform Films For RapidDissolve Dosage Form Incorporating Taste-Masking Compositions)”的PCT申请WO2003/030883中公开了采用掺入具有掩味包衣的膜中的微粒活性剂的组合物,该PCT申请的整个主题以引用方式并入本文。如在本申请中使用的,对通过对微粒活性剂进行包衣来进行掩味的任何提及也应理解为包括微粒活性剂的控释包衣。
对于涉及控释或掩味颗粒技术的基于膜的药品递送组合物的重要考虑是,含药物的颗粒在制造过程的混合和成膜操作期间保持化学上稳定并且不释放活性药品。因此,对于通过湿式流延法形成的膜、在膜成形步骤以及流延和干燥步骤之前,控释或掩味颗粒组合物应在混合器中足够稳定,以使颗粒在成品产品中保持完整。在热熔挤出膜制造过程中,颗粒必须在挤出装置和任何后续步骤中是稳定的,以便颗粒在成品产品中保持完整。
在一个实施方案中,掩味剂或控释剂是微粒生物效应剂上的薄膜包衣。在该实施方案中有用的包衣包含聚合物和非聚合物材料。
聚合物的非限制性示例包括丙烯酸类聚合物、纤维素聚合物或乙烯基聚合物。非聚合材料的非限制性示例包括冠醚、完全氢化的油和蜡。此外、掩味剂可为水溶性、水不溶性或部分水溶性的。
例如,包衣材料可为羧甲基纤维素;甲基纤维素;乙基纤维素;羟甲基纤维素;羟乙基纤维素;羟丙基纤维素;羟丙基甲基纤维素;羟甲基丙基纤维素;阿拉伯树胶;黄原胶;黄蓍胶;金合欢树胶;角叉菜胶;瓜尔胶;刺槐豆胶;果胶;藻酸盐;糊化、改性或未改性的淀粉,包括木薯淀粉、米淀粉、玉米淀粉、马铃薯淀粉和小麦淀粉;聚乙烯醇;聚丙烯酸;聚乙烯吡咯烷酮;聚(甲基)丙烯酸酯;聚(甲基)共聚物;糊精;右旋糖酐;蛋白质,诸如明胶、玉米蛋白、面筋、大豆蛋白、大豆分离蛋白和乳清蛋白;乳清蛋白分离物;酪蛋白;莱文(levin);胶原;甲壳素;壳聚糖;聚葡萄糖,和它们的组合。
有用的丙烯酸类聚合物包括可从America,LLC以商品名获得的那些,诸如以商品名EudragitEudragitEudragit和Eudragit出售的甲基丙烯酸共聚物,以及以商品名Eudragit出售的聚丙烯酸乙酯-甲基丙烯酸甲酯。这些丙烯酸类聚合物通常是水溶性材料。
有用的纤维素聚合物包括烷基纤维素,诸如甲基或乙基纤维素;以及羟烷基纤维素,诸如羟甲基纤维素、羟乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素、羟甲基丙基纤维素,和它们的组合。有用的烷基纤维素包括由Dow Chemicals以商品名Methocel ETM出售的那些。另外,有用的乙基纤维素可以商标名Aquacoat ECD从FMC Corporation商购获得。这些聚合物通常是水溶性材料。
此外,可将药物活性剂用被认为对人类食用安全并且相对稳定的完全氢化的油或蜡喷涂并凝结。有用但非限制性的药学上可接受的油包括矿物油、花生油、大豆油、向日葵油、玉米油、橄榄油、硬棕榈油和菜籽油。
在一些实施方案中,如例如在欧洲专利号EP1267829B1中已公开的,影响掩味的上述聚合物包衣可为与使用离子交换树脂的络合相比期望的,因为与使用离子交换树脂的络合相比,使用聚合物时可能有高药物载量。尽管有相反的申辩,但是我们已经发现离子交换树脂上的最高有用药品载量为约30重量%。相比之下,本发明的颗粒包衣可以50-95%的药品载量使用,这意味着经掩味的颗粒可含有至多约95重量%的活性物质和少至5重量%的掩味聚合物。这是与已知的离子交换树脂相比实质上更大的药物载量,并且在膜剂量单位的大小和重量有限的情况下非常重要,其中最大化进入均匀膜中的药物载量是重要的考虑因素。
在一些实施方案中,掩味剂或控释剂可以颗粒的约5-80重量%的量存在。在另一个实施方案中,掩味剂以颗粒的约5-60重量%的量存在。在另一个实施方案中,掩味剂以颗粒的约25-35重量%的量存在。经掩味的包衣颗粒中药品的精确载量是许多参数的函数,该许多参数包括药品、包衣以及颗粒或成膜基质中存在的任何调味品。
可以通过多种技术用上述掩味剂对药物活性剂进行掩味。该技术用掩味剂对药物活性剂或药物活性剂的部分进行包衣,以避免令人不快的味道效果,诸如苦味,该令人不快的味道效果通常与药物活性剂或药品相关联。有用的包衣技术包括但不限于流化床包衣、喷雾凝结包衣、附聚或造粒包衣、包埋包衣、共加速包衣、注入包衣、旋涂包衣、离子交换包衣等。
流化床包衣方法通常在制药工业中用于对药物活性剂进行掩味。流化床包衣机通过将连续的工艺气体流引入腔室来实现药物活性剂的流体化。包衣材料当通过包衣材料的喷涂路径时会沉积到混悬剂上。将经包衣的试剂干燥。相对低水溶性的聚合物通常用于对活性颗粒的表面进行包衣。粒径的最小极限为约100微米至120微米。由于工艺限制和产品损失,难以获得更小的粒径。使用这种方法,水不溶性药物活性剂可以适合地用水溶性掩味剂包被。
在喷雾凝结法中,将药物活性剂和包衣材料两者同时喷雾到供应有工艺气体的腔室中,以产生经均匀包衣的活性物质。该方法通常包括用可在合理的温度下熔融的材料对活性物质进行包衣,该材料为例如脂肪材料或聚合物,诸如某些聚合物。将材料混合物通过细喷嘴喷雾,并通过温度受控的气流或冷表面冷却。考虑混合物温度是重要的。所选包衣剂的熔融温度不应超过药物活性剂的降解温度。
在附聚或制粒方法中,通过机械手段或通过喷雾干燥将药物活性剂与掩味剂和溶剂混合。通过真空或加热或两者逐渐去除溶剂。然后使颗粒附聚。附聚的颗粒通常没有完全被掩味剂包被,并且因此可能会导致一些苦味。然而,通过将此类经包衣的颗粒掺入本发明的膜剂中可进一步降低苦味。
在典型的包埋包衣方法中,必须首先选择某些具有可以将药物活性剂捕获到其分子笼中的特定特性的化合物。化合物,如某些特别制作的淀粉和冠醚类分子,诸如环糊精和沸石,可用于此方法。通过离子吸引来包埋化合物和试剂。然后,将经包埋的试剂从溶液中沉淀出来。
凝聚包衣方法使用在溶液中的两种带相反电荷的聚合物。当该溶液被中和时,不溶性基质将从溶液中沉淀出来并将药物活性剂捕获在该不溶性基质中。示例包括阿拉伯树胶和明胶溶液的相互作用以及环糊精和蛋白质溶液的相互作用。
在注入方法中,将药物活性剂和调味品或甜味剂溶解并注入到聚合物基质中以形成干粉。在旋涂包衣方法中,将药物活性剂与糖或脂肪组合并旋转成经包衣的颗粒。该方法的细节公开在美国专利号5,028,632中,该美国专利的内容以引用方式并入本文。在离子交换包衣中,药物活性剂与离子交换树脂的离子键掩盖了该药物活性剂的味道。
挤出和滚圆法也可用于对药物活性微粒进行掩味。首先混合一定比率的一种或多种活性物质和一种或多种聚合物(诸如,淀粉、纤维素、树胶和/或它们的组合),并通过添加少量水使其增稠。然后将增稠的混合物通过单喷嘴螺杆或双喷嘴螺杆挤出。通过工艺形成球形小颗粒。通过过程控制和微粒筛分获得期望粒径。
冻干(冷冻干燥)方法也可用于本发明的实践中。将一种或多种聚合物(诸如,淀粉、树胶、纤维素和/或它们的组合)与一种或多种活性物质的组合混合并在水性介质中溶解(或分散)。然后将该混合物在预成型基材上冷冻干燥。可通过过程控制和产品筛分获得期望粒径。
在一些情况下,掩味可能等于将两种组分加在一起,这两种组分的味道都不是特别令人愉悦,但是由于它们的化学组成,它们彼此抵消或允许添加一种或多种第三物质而不会使味道的令人愉悦性随之降低。
本发明的食用水溶性递送系统还包含选自以下的一个或多个成员:消泡剂、增塑剂、表面活性剂、乳化剂、增稠剂、粘合剂、冷却剂、唾液刺激剂、甜味剂、抗微生物剂、抗原,和它们的组合。
用于本发明的颗粒的粒径理想地小于约200微米,并且掩味剂以颗粒的约15-80重量%的量存在。约150微米或更小的粒径也是可用的。理想地,颗粒的粒径为约100微米或更小。理想地,膜的厚度小于约380微米,例如小于约250微米。此外,掩味剂可以颗粒的约20-60重量%的量存在。理想地,掩味剂以颗粒的约25-35重量%的量存在。
在一些实施方案中,包被有掩味或控释聚合物的微粒生物效应剂的粒径可介于50微米至250微米之间。理想地,微粒和掩味剂的组合的大小具有150微米或更小,例如100微米或更小的粒径。小于50微米的粒径在一些实施方案中可能是不合适的,因为由于大表面积而使包被此类小颗粒是无效的。
在一些实施方案中,大于250微米的粒径可能是不合适的,因为较大的颗粒可在膜形成过程期间“桥接”,这意味着颗粒可从膜的底表面延伸到顶表面,或甚至突出超过膜的表面。此类桥接可导致成品膜的条纹显现和不均匀性。任何突出的颗粒也可能经受环境压力和过早分解,从而导致投配的不均匀性。
上述颗粒可为球形的、基本上球形的或非球形的,诸如不规则形状的颗粒或椭圆形状的颗粒。椭圆形状的颗粒或椭圆体是特别期望的,因为与球形颗粒相比,它们倾向于沉降至较小程度,从而能够在成膜基质中保持均匀性。
当膜中存在活性剂时,每单位面积的活性物质的量由膜的均匀分布决定。例如,当将膜切成单独剂型时,可非常精确地知道剂型中活性物质的量。这是因为给定区域中的活性物质的量与膜的另一部分中相同尺寸的区域中的活性物质的量基本上相同。当活性物质为药物,即药品时,剂量准确性为特别有利的。
均匀性由整个基质中不超过10重量%的药品差异决定。理想地,药品差异小于5重量%、小于2重量%、小于1重量%、或小于0.5重量%。此外,微粒的粒径为200微米或更小。此外,膜基质的厚度理想地小于约380微米。
添加剂
可掺入本发明组合物中的多种添加剂可提供多种不同的功能。添加剂类别的示例包括赋形剂、润滑剂、缓冲剂、稳定剂、发泡剂、颜料、着色剂、填写剂、疏松剂、甜味剂、调味剂、调味品、释放改性剂、佐剂、增塑剂、流动促进剂、脱模剂、多元醇、成粒剂、稀释剂、粘合剂、缓冲剂、吸收剂、助流剂、粘结剂、抗粘剂、酸化剂、软化剂、树脂、缓和剂、溶剂、表面活性剂、乳化剂、弹性体,以及它们的混合物。这些添加剂可在活性成分之前或与活性成分一起添加。
调味品
调味品可以选自天然和合成的调味液。此类试剂的说明性列表包括挥发性油、合成调味油、调味芳香剂、油、液体、油性树脂,或从植株、叶、花、果实、茎干得到的提取物,和它们的组合。示例的非限制性代表性列表包括薄荷精油、可可精油和柑橘精油,诸如柠檬、橙子、葡萄、酸橙和葡萄柚精油,以及水果香精,包括苹果、梨、桃、葡萄、草莓、覆盆子、樱桃、李子、菠萝、杏或其他水果味调味品。
有用的调味品或调味剂包括天然调味品和人工调味品。这些调味品可选自合成调味油和调味芳香剂,和/或油、油性树脂,和从植株、叶子、花、果实等得到的提取物,和它们的组合。非限制性调味油包括:留兰香薄荷精油、肉桂精油、胡椒薄荷精油、丁香精油、月桂精油、百里香精油、雪松叶精油、肉豆蔻精油、鼠尾草精油和苦杏仁精油。人造、天然或合成的水果调味品也是有用的,例如香草、巧克力、咖啡、可可和柑橘油,包括柠檬、橙子、葡萄、酸橙和葡萄柚精油,以及水果香精、包括苹果、梨、桃子、草莓、覆盆子、樱桃、李子、菠萝、杏等。这些调味品可单独或组合地使用。常用的调味品包括薄荷(诸如胡椒薄荷)、人工香草精、肉桂衍生物和各种水果调味品,无论是单独还是组合地采用。也可使用诸如醛类和酯类的调味品,包括乙酸肉桂酯、肉桂醛、柠檬醛、二乙缩醛、乙酸二氢香芹酯、甲酸丁香酯、对甲基苯甲醚等。醛调味品的其他示例包括但不限于乙醛(苹果);苯甲醛(樱桃、杏仁);肉桂醛(肉桂);柠檬醛,即α柠檬醛(柠檬、酸橙);橙花醛,即β柠檬醛(柠檬、酸橙);癸醛(橙子、柠檬);乙基香兰素(香草精、奶油);洋茉莉醛,即胡椒醛(香草精、奶油);香兰素(香草精、奶油);α-戊基肉桂醛(辛辣果味);丁醛(黄油、奶酪);戊醛(黄油、奶酪);香茅醛(改性剂,很多类型);癸醛(柑橘类水果);醛C-8(柑橘类水果);醛C-9(柑橘类水果);醛C-12(柑橘类水果);2-乙基丁醛(浆果);己烯醛,即反式-2(浆果);甲苯基醛(樱桃、杏仁);藜芦醛(香草);12,6-二甲基-5-庚烯醛,即甜瓜醛(甜瓜);2二甲基辛醛(绿色水果);和2-十二烯醛(柑橘、中国柑桔);樱桃;葡萄;它们的混合物;等等。
其他有用的调味品包括醛和酯,诸如苯甲醛(樱桃、杏仁);柠檬醛,即α-柠檬醛(柠檬、酸橙);橙花醛,即β-柠檬醛(柠檬、石灰);癸醛(橙色、柠檬);醛C-8(柑橘类水果);醛C-9(柑橘类水果);醛C-12(柑橘类水果);甲苯基醛(樱桃、杏仁);2,6-二甲基辛醇(绿色水果);和2-十二烯醛(柑橘、中国柑桔);它们的组合等。
所采用的调味品的量通常是偏好的量,取决于诸如调味品类型、单独调味品和所需强度的因素。为了获得最终产品中所需的结果,可改变用量。此类改变在本领域技术人员的能力之内,而无需过度实验。通常,约0.1重量%至约30重量%的量可用于实践本发明。
甜味剂
合适的甜味剂包括天然甜味剂和人造甜味剂两者。合适的甜味剂的非限制性示例包括例如:水溶性甜味剂,诸如单糖、二糖和多糖,例如木糖、核糖、葡萄糖(右旋糖)、甘露糖、半乳糖、果糖(左旋糖)、蔗糖(糖)、高果糖玉米糖浆、麦芽糖、转化糖(果糖和从蔗糖衍生的葡萄糖的混合物)、部分水解的淀粉、玉米糖浆固体和二氢查耳酮;水溶性人造甜味剂,诸如可溶性糖精盐、即糖精钠或钙盐、甜蜜素盐、3,4-二氢-6-甲基-1,2,3-氧杂噻嗪-4-酮-2,2-二氧化物的钠、铵或钙盐、3,4-二氢-6-甲基-1,2,3-氧杂噻嗪-4-酮-2,2-二氧化物的钾盐(乙酰舒泛-K)、糖精的游离酸形式等;基于二肽的甜味剂,诸如L-天冬氨酸衍生的甜味剂,例如L-天冬氨酰-L-苯丙氨酸甲酯(天冬甜素)、L-α-天冬氨酰-N-(2,2,4,4-四甲基-3-硫杂环丁烷基)-D-丙氨酰胺水合物、L-天冬氨酰-L-苯基甘油和L-天冬氨酰-L-2,5-二氢苯基甘氨酸、L-天冬氨酰-2,5-二氢-L-苯丙氨酸、L-天冬氨酰-L-(1-环己烯)-丙氨酸等;由天然存在的水溶性甜味剂衍生的水溶性甜味剂,诸如普通糖(蔗糖)的氯化衍生物,被称为例如三氯蔗糖;以及基于蛋白质的甜味剂,诸如thaurnatoccous danielli(奇异果甜蛋白I和II)。也可以使用天然存在的高强度甜味剂,诸如罗汉果、甜叶菊、甜菊糖、莫奈菌素和甘草甜素。
通常,有效量的辅助甜味剂用于提供特定组合物所需的甜味水平,并且该量将随所选的甜味剂而变化。该量将通常为组合物的0.01重量%至约10重量%。这些量可用于实现所需的甜度水平,而与从使用的任何任选调味油获得的风味水平无关。当然,不需要将甜味剂添加到旨在用于非口服施用的膜中。
着色剂
可用于本发明的颜色添加剂包括食品、药品和化妆品颜料(FD&C)、药品和化妆品颜料(D&C)或外用药品和化妆品颜料(Ext.D&C)。这些颜料为染料、它们的对应色淀、以及某些天然和衍生的着色剂。色淀是吸收到氢氧化铝上的染料。
着色剂的其他示例包括已知的偶氮染料、有机或无机色素、或天然来源的着色剂。无机颜料是优选的,例如氧化物或铁或钛,这些氧化物的添加浓度基于所有组分的重量在约0.001%至约10%,优选约0.5%至约3%的范围内。
对本文所述的本发明的实施方案的说明意图提供各种实施方案的结构的一般了解,且所述说明并不意图充当可能利用本文所描述结构的装置和系统的所有元件和特征的完整描述。根据本文的教导,许多其他实施方案对于本领域技术人员将变得显而易见。其他实施方案可被利用且由此导出,使得可在不偏离本公开的范围的情况下进行结构和逻辑替代和改变。附图也仅是代表性的,并且不一定按比例绘制。为了使本发明的实施方案易于解释,可能放大了某些比例,而减小了其他比例。因此,本说明书和附图将视为说明性的,而非限制性的。
本发明主题的此类实施方案在本文中个别地和/或共同地通过术语“实施方案”来引用,其仅仅为了方便且不意图将本申请的范围主动限制到任一单个实施方案或发明概念(如果实际上示出了多于一个发明)。因此,尽管本文已说明和描述了具体的实施方案,但应了解,计划来实现相同目的的任何布置代替所展示的具体实施方案。本发明意图涵盖各种实施方案的任何和所有改变或变体。本领域的技术人员将通过审阅以上描述而显而易见以上实施方案和本文未特定描述的其他实施方案的组合。
在上文详细描述中,可以看出,出于合理化本公开目的,各种特征共同组合在各种实施方案中。本公开的这种方法不应解释为反映了以下意图:所要求保护的实施方案具有比每项权利要求中明确叙述的特征更多的特征。而是,如以下权利要求书所反映的,发明性主题所仰赖于的要少于单个实施方案的所有特征。因此,随附权利要求书均在此并入具体实施方式中,其中每项权利要求自身可作为单独的实施方案。
实验
实施例1:
图3是计算系统100的形式的机器的实施方案的方框图,其中是一组指令102,该组指令当被执行时使机器执行根据本发明的实施方案的方法中的任何一个或多个方法。在一些实施方案中、机器作为独立设备运行。在一些实施方案中、该机器(例如、经由网络122)连接至其他机器。在网络化的实现方式中、机器在服务器-客户端用户网络环境中以服务器或客户端用户机器的能力运行。本发明所考虑的机器的示例性实施方式包括但不限于服务器电脑、客户端用户电脑、个人电脑(PC)、平板电脑、个人数字助理(PDA)、蜂窝电话、移动设备、掌上型电脑、膝上型电脑、台式电脑、通信设备、个人受信设备、Web设备、网络路由器、交换机或网桥、或任何能够执行一组指令(顺序指令或其他指令)的机器,这些指令指定了该机器要执行的动作。
计算系统100包括处理设备104(例如、中央处理单元(CPU)、图形处理单元(GPU)或两者)、程序存储设备106和数据存储设备108,这些设备通过总线110与彼此通信。计算系统100还包括显示设备112(例如、液晶显示器(LCD)、平板、固态显示器、或阴极射线管(CRT))。计算系统100包括输入设备116(例如、键盘);光标控制设备126(例如、鼠标);磁盘驱动器单元114;信号生成设备118(例如、扬声器和遥控器;以及网络接口设备124,这些设备通过总线110可操作地耦接在一起和/或与其他功能区块可操作地耦接。磁盘驱动器单元114包括机器可读介质120,在其上存储了体现本文的方法或功能中的任何一种或多种方法或功能(包括本文所说明的那些方法)的一组或多组指令102(例如,软件)。指令102还由计算系统100在执行期间完全或至少部分地驻留在程序存储设备106、数据存储设备108和/或处理设备104内。程序存储设备106和处理设备104也构成机器可读介质。诸如但不限于专用集成电路、可编程逻辑阵列和其他硬件设备之类的专用硬件实施方式同样可以被构造为实施本文所述的方法。包括各种实施方案的装置和系统的应用广泛地包括各种电子和电脑系统。一些实施方案使用相关的控件和数据信号在两个或更多个特定的互连硬件模块或设备中实现功能,该使用相关的控件和数据信号在模块之间并通过模块进行通信,或者作为专用集成电路的一部分。因此,示例性系统可适用于软件、固件和硬件实现方式。
根据各种实施方案,本文所述的方法、功能或逻辑被实现为在电脑处理器上运行的一个或多个软件程序。包括但不限于专用集成电路、可编程逻辑阵列和其他硬件设备之类的专用硬件实施方式同样可以被构造为实施本文所述的方法。此外,还可构造替代软件实现方式,包括但不限于分布式处理或部件/对象分布式处理、并行处理或虚拟机处理,以实现本文所述的方法、功能或逻辑。
该实施方案设想了一种机器可读介质或电脑可读介质,该机器可读介质或电脑可读介质包含指令102,或从传播的信号接收并执行指令102,以便连接到网络环境122的设备可发送或接收语音、视频或数据,以及使用指令102在网络122上进行通信。经由网络接口设备124在网络122上进一步发送或接收指令102。机器可读介质还包含用于存储数据的数据结构,该数据结构在本文的系统和方法的说明性实施方案中可用于提供数据与机器或电脑之间的功能关系。
尽管在示例实施方案中将机器可读介质120示出为单个介质,但是术语“机器可读介质”应被认为包括存储一组或多组指令的单个介质或多个介质(例如,集中式或分布式数据库,和/或关联的缓存和服务器)。术语“机器可读介质”还应被认为包括任何能够存储、编码或携带一组指令以供机器执行并且使机器执行实施方案的方法中的任何一种或多种方法的介质。因此,术语“机器可读介质”应被认为包括但不限于:固态存储器,例如存储卡或容纳一个或多个只读(非易失性)存储器、随机访问存储器或其他可重写(易失性)存储器的其他包装;磁光或光学介质,例如磁盘或磁带;和/或电子邮件或其他自包含信息归档或归档集的数字文件附件被视为等同于有形存储介质的分发介质。因此,该实施方案被认为包括本文列出的有形机器可读介质或有形分发介质中的任何一者或多者,并且包括存储了本文的软件实现方式的本领域公认的等同物和后继介质。
还应当注意,实现本文的方法、功能或逻辑的软件任选地存储在有形存储介质上,例如:磁介质,例如磁盘或磁带;以及磁光或光学介质,例如磁盘;或固态介质,例如存储卡或容纳一个或多个只读(非易失性)存储器、随机存取存储器或其他可重写(易失性)存储器的其他包装。电子邮件或其他独立信息档案或档案集的数字文件附件被视为等同于有形存储介质的分发介质。因此,本公开被认为包括本文列出的有形存储介质或分发介质以及其他等同和后继介质,该介质中存储了本文的软件实现。
如前所述,尽管说明书参考特定的标准和协议描述了根据本发明的实施方案实现的部件和功能,但是实施方案不限于此类标准和协议。
提供摘要以符合37 C.F.R.§1.72(b)的要求,其要求应允许读者快速地确定技术公开的性质的摘要。提交时应理解的是,它不应被用来解释或限制权利要求书的范围或含义。此外,在以上具体实施方式中,可以看出、为达精简本公开的目的,各种特征被一起分组在单个实施方案中。本公开的这种方法不应解释为反映了以下意图:所要求保护的实施方案要求比每项权利要求中明确叙述的特征更多的特征。而是,如以下权利要求书所反映的,发明性主题所仰赖于的要少于单个实施方案的所有特征。因此、以下权利要求均在此并入具体实施方式中,其中每项权利要求自身可作为单独要求保护的主题。
虽然已经描述了具体示例性实施方案,但将明显的是,在不背离本文描述的发明性主题的更广泛的范围的情况下,可对这些实施方案做出各种的修改和更改。因此,本说明书和附图将视为说明性的,而非限制性的。形成本文一部分的附图借助于说明而非限制的方式来展示实践主题的特定实施方案。充分详细地描述所示出的实施方案以使本领域技术人员能够实践本文的教导。其他实施方案可被利用且由此导出,使得可在不偏离本公开的范围的情况下进行结构和逻辑替代和改变。因此,不应以限制性意义来采用本具体实施方式,且各种实施方案的范围仅通过随附权利要求书连同此类权利要求书授权的等效物的全部范围来限定。
给定本文提供的本发明的教导,本领域普通技术人员将能够考虑本发明的技术的其他实现方式和应用。尽管本文已经参考附图描述了本发明的说明性实施方案、但是应该理解,本发明不限于那些精确的实施方案、并且在不背离所附权利要求书的范围的情况下,本领域的技术人员可以在所述实施方案中做出各种其他改变和修改。
Claims (80)
1.一种用于创建一个或多个个性化个体单位剂量(IUD)的系统,所述IUD包含规定量的用于治疗个体的活性物质,所述系统包括:
用于制作所述个性化IUD的装置,所述装置选自由以下组成的组:成膜组件、胶囊填写组件、片剂成形组件、片剂包衣组件、共混(混合)组件、粉末成形组件、制粒组件、喷雾干燥组件、挤出机组件、配混组件、包装组件、贴标签组件、压花组件、刻痕组件、质量控制组件和它们的组合;以及
网络化系统,所述网络化系统被配置为以电子方式传送从所述个体测量的健康信息;
其中将所述健康信息以电子方式传送给确定医疗处方的医疗专业人员,所述医疗处方包括所述个性化IUD中的活性物质的所述规定量;并且
其中使用用于制作所述个性化IUD的装置来根据所述医疗处方制作所述IUD。
2.如权利要求1所述的系统,其中所述网络化系统包括处理器、记忆存储器和可执行指令;并且还包括显示设备、字母数字输入设备、光标控制设备、驱动单元、机器可读介质和信号生成设备中的至少一者。
3.如权利要求1所述的系统,所述系统包括生物特征测量模块,所述生物特征测量模块与所述个体对接。
4.如权利要求3所述的系统,其中所述生物特征测量模块包括侵入性测量设备和非侵入性测量设备。
5.如权利要求3所述的系统,其中所述生物特征测量模块包括选自由以下组成的组的设备:声学仪器、视觉仪器、触觉仪器、化学仪器、生物仪器、电气仪器、热仪器和它们的组合。
6.如权利要求3所述的系统,其中所述生物特征测量模块包括选自由以下组成的组的设备:摄像机、视频示波器、照明系统、比色计、肺活量计、霍尔特氏动态心电监测仪、生命体征监测仪、信号监测仪、传感器、超声波探头、测量来自身体的电信号的机器、血液化学仪器、血流测量设备、血液含量测量设备、热测量设备和它们的组合。
7.如权利要求3所述的系统,其中所述生物特征测量模块包括选自由以下组成的组的设备:脑电图(EEG)机器;心电图(EKG)机器;肌电图(EMG)机器;超声心动图(ECG)机器;心房纤颤设备;听诊器;咽镜;鼻窦镜;耳镜;腹腔镜;皮肤镜;血气测量设备;多用途摄像机;视网膜摄像机;眼睛测量设备;口内摄像机;腹部超声波设备;血管超声波设备;经阴道超声波设备;测量温度、血流量、血糖、肤色、肌理、血脂含量、血液胆固醇含量中的一者或多者的皮肤表面测量设备;加速度计;运动传感器,和它们的组合。
8.如权利要求3所述的系统,其中所述生物特征测量模块包括移动设备,所述移动设备包括一个或多个软件应用程序,所述一个或多个软件应用程序用于获得生物特征信息、用于进行诊断的信息、用于医学评估的信息、用于评估所述个体所需的治疗效果和/或治疗变化的信息,或它们的组合。
9.如权利要求8所述的系统,其中所述移动设备选自由以下组成的组:移动电话、平板电脑、膝上型电脑、手表和可穿戴设备。
10.如权利要求1所述的系统,其中所述医疗处方还包含载体基质的药物制剂。
11.如权利要求10所述的系统,其中所述药物制剂包含所述活性物质。
12.如权利要求10所述的系统,其中所述载体基质包括选自由以下组成的组的聚合物:聚环氧乙烷(PEO)、支链淀粉、羟丙基甲基纤维素(HPMC)、羟乙基纤维素(HPC)、羟丙基纤维素、聚乙烯吡咯烷酮、羧甲基纤维素、聚乙烯醇、海藻酸钠、聚乙二醇、黄原胶、黄蓍胶、瓜尔胶、金合欢树胶、阿拉伯树胶、聚丙烯酸、甲基丙烯酸甲酯共聚物、羧乙烯基共聚物、淀粉、明胶、乙基纤维素、羟丙基乙基纤维素、醋酸邻苯二甲酸纤维素、羟丙基甲基纤维素邻苯二甲酸酯,和它们的组合。
13.如权利要求10所述的系统,其中所述载体基质包括选自由以下组成的组的聚合物:聚(乙醇酸)(PGA)、聚(乳酸)(PLA)、聚二噁烷、聚草酸酯、聚(α-酯)、聚酸酐、聚乙酸酯、聚己内酯、聚(原酸酯)、聚氨基酸、聚氨基碳酸酯、聚氨酯、聚碳酸酯、聚酰胺、聚(氰基丙烯酸烷基酯),以及它们的混合物和共聚物。
14.如权利要求10所述的系统,其中所述载体基质包括选自由以下组成的组的聚合物:L-乳酸和D-乳酸的立体聚合物、双(对羧基苯氧基)丙烷酸和癸二酸的共聚物、癸二酸的共聚物、己内酯的共聚物、聚(乳酸)/聚(乙醇酸)/聚乙二醇共聚物、聚氨酯和(聚(乳酸)的共聚物、聚氨酯和(聚乳酸)的共聚物、α-氨基酸的共聚物、α-氨基酸和己酸的共聚物、谷氨酸α-苄酯和聚乙二醇的共聚物、琥珀酸酯和聚(乙二醇)的共聚物、聚磷腈、多羟基链烷酸酯、丙交酯/乙交酯共聚物、聚酸酐,和它们的组合。
15.如权利要求10所述的系统,其中所述载体基质包括选自由以下组成的组的聚合物:多糖、树胶,和它们的组合。
16.如权利要求10所述的系统,其中所述药物制剂包含选自由以下组成的组的溶剂:水、醇、丙酮、二氯甲烷,和它们的组合。
17.如权利要求10所述的系统,其中所述药物制剂包含选自由以下组成的组的组分:佐剂、渗透促进剂、增塑剂、增稠剂、流变改性剂、溶剂、醇、增量剂、着色剂、颜料、甜味剂、调味剂,和它们的组合。
18.如权利要求11所述的系统,其中所述活性物质选自由以下组成的组:小分子、大分子、生物制品、微生物、过敏原、酶,和它们的组合。
19.如权利要求10所述的系统,其中所述活性物质是选自由以下组成的组的药物或生物活性物质:血管紧张素转化酶抑制剂、抗心绞痛药、抗心律失常药、抗哮喘剂、抗高胆固醇血症药、镇痛剂、麻醉剂、抗惊厥药、抗抑郁剂、抗糖尿病剂、抗腹泻制剂、解毒剂、抗组胺剂、抗高血压药、抗炎剂、抗脂质剂、抗躁狂剂、抗呕吐剂、抗中风剂、抗甲状腺制剂、抗肿瘤药、抗病毒剂、痤疮药、生物碱、氨基酸制剂、镇咳剂、抗高尿酸血症药、抗病毒药、合成代谢制剂、全身性和非全身性抗感染剂、抗赘瘤剂、抗帕金森症药剂、抗风湿剂、食欲刺激剂、生物反应调节剂、血液调节剂、骨代谢调控剂、心血管药剂、中枢神经系统刺激剂、胆碱酯酶抑制剂、避孕药、解充血剂、膳食补充剂、多巴胺受体激动剂、子宫内膜异位控制剂、勃起功能障碍治疗剂、致育剂、胃肠道药剂、顺势治疗剂、激素、高血钙症和低血钙症控制剂、免疫调节剂、免疫抑制剂、偏头痛制剂、运动病治疗剂、肌肉松弛剂、肥胖控制剂、骨质疏松制剂、催产素、副交感神经剂、拟副交感神经剂、前列腺素、心理治疗剂、呼吸道药剂、镇静剂、戒烟辅助剂、交感神经阻滞剂、震颤制剂、尿路药剂、血管扩张剂、轻泻剂、抗酸剂、离子交换树脂、退热剂、食欲抑制剂、祛痰剂、抗焦虑剂、抗溃疡剂、抗炎物质、冠状血管扩张剂、脑扩张剂、外周血管扩张剂、精神病药剂、剌激剂、抗高血压药、血管收缩剂、偏头痛治疗剂、抗生素、镇定剂、抗精神病剂、抗肿瘤药、抗凝血剂、抗血栓药、催眠药、止吐剂、抗恶心剂、抗惊厥剂、神经肌肉药、高血糖和低血糖药剂、甲状腺和抗甲状腺制剂、利尿剂、抗痉挛剂、子宫松弛药、抗肥胖药、促红细胞生成药、抗哮喘剂、咳嗽抑制剂、粘液溶解剂、DNA和遗传修饰药物,以及它们的组合。
20.如权利要求1所述的系统,其中所述IUD呈选自由以下组成的组的剂型:膜剂、糯米纸囊剂、胶囊剂、片剂、混悬剂、溶液剂、软膏剂、贴剂、乳膏剂、凝胶剂、锭剂、安瓿、药瓶、糖浆剂、酊剂、醑剂、糖锭、香膏、搽剂、注射剂,和它们的组合。
21.如权利要求1所述的系统,其中所述医疗处方包括药物活性物质、生物活性物质、前药、衍生物、类似物,或它们的组合。
22.如权利要求21所述的系统,其中所述药物活性物质或生物活性物质选自由以下组成的组:处方活性物质、OTC活性物质、顺势疗法活性物质,和它们的组合。
23.如权利要求1所述的系统,所述系统还包括将所述健康信息存储在数据库或网络系统中的步骤。
24.一种生产针对个体的含有活性物质的个性化IUD的方法,所述方法包括:
a)获得与所述个体的健康有关的生物特征测量结果;
b)将所述生物特征测量结果传输给医疗或处方产品的制造商;
c)根据针对所述个体具特异性的医疗处方制造所述IUD;以及
d)将根据所述医疗处方制成的所述IUD递送给所述个体。
25.如权利要求24所述的方法,所述方法还包括在将所述生物特征测量结果传输给所述制造商的所述步骤之前,将所述个体的所述生物特征测量结果以电子方式传输给被授权书写所述医疗处方的医疗专业人员的步骤。
26.如权利要求25所述的方法,所述方法还包括在制造所述IUD的所述步骤之前,将所述医疗处方以电子方式传输给所述制造商的步骤。
27.如权利要求26所述的方法,所述方法还包括在将所述医疗处方传输给所述制造商的所述步骤之前,对保险会员资格进行电子验证并确定所述个体的承保范围的步骤。
28.如权利要求24所述的方法,其中制造所述IUD的所述步骤包括使用选自由以下组成的组的装置:成膜组件、胶囊填写组件、片剂成形组件、片剂包衣组件、共混(混合)组件、粉末成形组件、制粒组件、喷雾干燥组件、挤出机组件、配混组件、包装组件、贴标签组件、压花组件、刻痕组件、质量控制组件,和它们的任何组合。
29.如权利要求28所述的方法,其中制造所述IUD的所述步骤包括将所述活性物质添加至载体基质。
30.如权利要求29所述的方法,其中所述IUD是膜剂。
31.如权利要求28所述的方法,其中制造所述IUD的所述步骤还包括在一个或多个单独孔中形成所述IUD的步骤。
32.如权利要求29所述的方法,其中制造所述IUD的所述步骤还包括将所述活性物质添加到已经形成的IUD中的步骤。
33.如权利要求30所述的方法,其中所述膜剂是多层的,并且将所述活性物质掺入第二膜层中。
34.如权利要求32所述的方法,其中将所述活性物质包衣到所述IUD上。
35.如权利要求32所述的方法,其中将所述活性物质喷涂到所述IUD上。
36.如权利要求32所述的方法,其中将所述活性物质沉积到所述IUD上。
37.如权利要求32所述的方法,其中将所述活性物质印刷到所述IUD上。
38.如权利要求24所述的方法,其中所述IUD是选自由以下组成的组的剂型:膜剂、糯米纸囊剂、胶囊剂、片剂、混悬剂、溶液剂、软膏剂、贴剂、乳膏剂、凝胶剂、锭剂、安瓿、药瓶、糖浆剂、酊剂、醑剂、糖锭、香膏、搽剂、注射剂,和它们的组合。
39.如权利要求24所述的方法,所述方法还包括在递送所述IUD之前包装所述制造的IUD并在所述包装上标记每份IUD的活性物质的量的步骤。
40.如权利要求38所述的方法,其中所述IUD含有的活性物质的量在所述包装标签上印刷的量的约10%以内。
41.如权利要求24所述的方法,其中所述活性物质选自由以下组成的组:小分子、大分子、生物制品、微生物、过敏原、酶,和它们的组合。
42.如权利要求24所述的方法,其中所述活性物质是选自由以下组成的组的药物或生物活性物质:血管紧张素转化酶抑制剂、抗心绞痛药、抗心律失常药、抗哮喘剂、抗高胆固醇血症药、镇痛剂、麻醉剂、抗惊厥药、抗抑郁剂、抗糖尿病剂、抗腹泻制剂、解毒剂、抗组胺剂、抗高血压药、抗炎剂、抗脂质剂、抗躁狂剂、抗呕吐剂、抗中风剂、抗甲状腺制剂、抗肿瘤药、抗病毒剂、痤疮药、生物碱、氨基酸制剂、镇咳剂、抗高尿酸血症药、抗病毒药、合成代谢制剂、全身性和非全身性抗感染剂、抗赘瘤剂、抗帕金森症药剂、抗风湿剂、食欲刺激剂、生物反应调节剂、血液调节剂、骨代谢调控剂、心血管药剂、中枢神经系统刺激剂、胆碱酯酶抑制剂、避孕药、解充血剂、膳食补充剂、多巴胺受体激动剂、子宫内膜异位控制剂、勃起功能障碍治疗剂、致育剂、胃肠道药剂、顺势治疗剂、激素、高血钙症和低血钙症控制剂、免疫调节剂、免疫抑制剂、偏头痛制剂、运动病治疗剂、肌肉松弛剂、肥胖控制剂、骨质疏松制剂、催产素、副交感神经剂、拟副交感神经剂、前列腺素、心理治疗剂、呼吸道药剂、镇静剂、戒烟辅助剂、交感神经阻滞剂、震颤制剂、尿路药剂、血管扩张剂、轻泻剂、抗酸剂、离子交换树脂、退热剂、食欲抑制剂、祛痰剂、抗焦虑剂、抗溃疡剂、抗炎物质、冠状血管扩张剂、脑扩张剂、外周血管扩张剂、精神病药剂、剌激剂、抗高血压药、血管收缩剂、偏头痛治疗剂、抗生素、镇定剂、抗精神病剂、抗肿瘤药、抗凝血剂、抗血栓药、催眠药、止吐剂、抗恶心剂、抗惊厥剂、神经肌肉药、高血糖和低血糖药剂、甲状腺和抗甲状腺制剂、利尿剂、抗痉挛剂、子宫松弛药、抗肥胖药、促红细胞生成药、抗哮喘剂、咳嗽抑制剂、粘液溶解剂、DNA和遗传修饰药物,以及它们的组合。
43.如权利要求24所述的方法,其中通过民营快递、联邦快递、无人机、UPS或国家邮政服务进行递送。
44.如权利要求24所述的方法,其中制造所述IUD包括以下步骤:
i)提供载体基质;
ii)将所述载体基质与所述活性物质组合;
iii)形成如在所述医疗处方中所阐述的所述IUD;以及
iv)包装所述IUD以供递送给所述个体。
45.如权利要求44所述的方法,其中所述载体基质为膜或片层的形式。
46.如权利要求44所述的方法,其中所述载体基质以多个单位提供,其中每个单位含有根据所述医疗处方的量的所述载体基质。
47.如权利要求46所述的方法,其中所述载体基质的所述多个单位是从膜或片层上切下的。
48.如权利要求46所述的方法,其中所述载体基质的所述多个单位中的每一个单位均提供在单独模具中。
49.如权利要求48所述的方法,所述方法包括将所述规定量的活性物质添加到含有所述载体基质的所述单独模具中以制造IUD。
50.如权利要求49所述的方法,所述方法包括将所述IUD单独沉积到包装材料上。
51.如权利要求47所述的方法,其中将所述载体基质与所述活性物质组合包括将所述规定量的活性物质喷涂到所述多个单位中的每一个单位上。
52.如权利要求44所述的方法,其中制造所述IUD的所述步骤是在药物配制人员的监督下执行的。
53.如权利要求44所述的方法,所述方法还包括以下步骤:共包装多个制造的IUD以供递送给所述个体,每个制造的IUD基于针对所述个体具特异性的一个或多个处方。
54.如权利要求53所述的方法,其中在所述多个制造的IUD中的每一个制造的IUD的包装中进行颜色编码以向所述个体提供药物使用说明。
55.如权利要求53所述的方法,其中在所述多个制造的IUD中的每一个制造的IUD的所述包装上或在实际的IUD上印刷可扫描代码,使得所述个体的移动设备可扫描所述代码以检索药物信息和使用说明。
56.如权利要求55所述的方法,其中所述可扫描代码是QR代码。
57.如权利要求25所述的方法,其中将所述信息发送给所述医疗专业人员包括使用电信设备。
58.如权利要求24所述的方法,其中所述医疗处方包含有待以所述IUD施用给所述个体的多于一种活性物质。
59.一种用于创建一个或多个含有规定量的活性物质的个性化个体单位剂量(IUD)以供分发和施用给个体的方法,所述方法包括:
(a)向医疗专业人员提供所述个体的个人健康信息;
(b)由所述医疗专业人员开出医疗处方,所述医疗处方包括至少部分地根据所述个人健康信息确定的有待施用给所述个体的活性物质的量,所述医疗处方包括用于根据个性化个体单位剂量(IUD)施用规定量的所述活性物质的治疗方案;
(c)将所述医疗处方的至少部分以电子方式传送给IUD的制造商;
(c)使用用于制造个性化IUD的装置制造所述IUD;以及
(d)将所述IUD分发给所述个体。
60.如权利要求59所述的方法,其中所述装置选自由以下组成的组:成膜组件、胶囊填写组件、片剂成形组件、片剂包衣组件、共混(混合)组件、粉末成形组件、制粒组件、喷雾干燥组件、挤出机组件、配混组件、包装组件、贴标签组件、压花组件、刻痕组件、质量控制组件,和它们的组合。
61.如权利要求60所述的方法,其中经由网络化系统向所述医疗专业人员提供所述个人健康信息。
62.如权利要求60所述的方法,其中制造所述IUD包括以下步骤中的一个或多个步骤:
(1).向所述装置中的一个或多个装置提供载体基质;
(2).向所述装置中的一个或多个装置提供所述活性物质;
(3).在所述装置中的一个或多个装置中组合所述活性物质和所述载体基质;
(4).由所述载体基质和所述活性物质形成所述IUD;
(5).包装所述IUD以分发给所述个体。
63.一种处方执行系统,所述处方执行系统用于以电子方式创建处方,以及通过根据所述处方的说明制造个性化IUD来填写所述处方,所述处方执行系统包括:
数据库管理系统,所述数据库管理系统包括多个数据库,所述多个数据库被配置为存储以电子方式生成所述处方、显示和管理所述处方和在所述处方中开出的药物、以及递送所述制造的个性化IUD所需的数据;
启用网络的控制系统,所述启用网络的控制系统可操作地链接至所述数据库管理系统,所述启用网络的控制系统包括一个或多个处理设备和多个模块,所述多个模块被配置为经执行以电子方式生成所述处方、显示和管理所述处方和在所述处方中开出的药物,以及递送所述制造的个性化IUD;以及
前端应用程序,所述前端应用程序被配置为向所述处方执行系统的多个参与者提供图形用户界面,以供以电子方式生成所述处方、显示和管理所述处方和在所述处方中开出的药物、递送所述制造的个性化IUD,以及在所述多个参与者之间进行通信和交互,
其中所述多个参与者是患者、医疗专业人员、保险提供商和IUD制造商。
64.如权利要求63所述的处方执行系统,所述处方执行系统还包括生物特征测量模块,所述生物特征测量模块被配置为可操作地链接至所述启用网络的控制系统并且被配置为与所述患者对接。
65.如权利要求64所述的处方执行系统,其中所述生物特征测量模块是可穿戴或不可穿戴的设备。
66.如权利要求63所述的处方执行系统,其中所述多个数据库包括用户帐户数据库、患者数据库、医疗信息数据库、处方数据库、保险信息数据库、和提醒通知数据库。
67.如权利要求66所述的处方执行系统,其中所述多个模块包括生物特征测量处理模块、处方处理模块、保险处理模块、和提醒通知模块。
68.如权利要求67所述的处方执行系统,其中所述生物特征测量处理模块被配置为处理从所述患者收集的生物特征测量信息并将经处理的生物特征测量信息存储在所述患者数据库中。
69.如权利要求67所述的处方执行系统,其中所述处方处理模块被配置为处理由所述医疗专业人员提供的处方信息并将经处理的处方信息存储在所述处方数据库中。
70.如权利要求67所述的处方执行系统,其中所述保险处理模块被配置为验证所述患者的保险计划,并基于所述患者的所述保险计划确定在所述处方中开出的所述药物的承保范围。
71.如权利要求67所述的处方执行系统,其中所述提醒通知模块被配置为生成各种通信提醒、将生成的提醒存储在所述提醒通知数据库中,以及将所述生成的提醒发送给适当的参与者。
72.如权利要求63所述的处方执行系统,其中所制造的个性化IUD由所述IUD制造商直接递送给所述患者。
73.如权利要求63所述的处方执行系统,其中所述前端应用程序包括处方生成页面、患者页面、患者处方页面、以及处方执行页面。
74.如权利要求73所述的处方执行系统,其中所述处方生成页面、患者页面、患者处方页面和处方执行页面可分别由所述医疗专业人员、患者、保险提供商和IUD制造商访问。
75.一种用于使用如权利要求63所述的处方执行系统以电子方式创建处方以及通过根据所述处方的说明制造个性化IUD来填写所述处方的方法,所述方法包括:
基于由医疗专业人员提供的信息和数据制定和创建处方;
由患者确定是否继续填写所述处方;
如果所述患者决定继续填写所述处方,则提醒IUD制造商基于所述处方的所述说明生产所述个性化IUD;
由保险提供商确定所述患者是否参加了由所述保险提供商提供的保险计划;
如果所述患者参加了由所述保险提供商提供的所述保险计划,则基于所述患者的所述保险计划确定在所述处方中开出的药物的承保范围并准备初步金额报告;以及
由所述IUD制造商生产、包装和递送所述制造的个性化IUD给所述患者。
76.如权利要求75所述的方法,其中所述方法还包括在基于由所述医疗专业人员提供的所述信息和数据制定和创建所述处方之后,提醒所述患者审查所述处方的步骤。
77.如权利要求76所述的方法,其中所述方法还包括如果所述患者决定不继续填写所述处方,则提醒所述医疗专业人员的步骤。
78.如权利要求77所述的方法,其中所述方法还包括提醒所述IUD制造商处理发票并将所述发票直接发送给所述患者的步骤。
79.如权利要求78所述的方法,其中所述方法还包括在基于所述患者的所述保险计划确定所述处方中开出的所述药物的承保范围之后,提醒所述患者所述初步金额报告准备好被查看的步骤。
80.如权利要求79所述的方法,其中所述方法还包括在生产、包装和递送所述制造的个性化IUD给所述患者之后,提醒所述患者、医疗专业人员和保险提供商通知将所述制造的个性化IUD递送给所述患者的步骤。
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AU2019288476A1 (en) | 2021-03-18 |
EP3811371A1 (en) | 2021-04-28 |
BR112021001738A2 (pt) | 2021-06-29 |
US11806311B2 (en) | 2023-11-07 |
US20190388302A1 (en) | 2019-12-26 |
CA3108304A1 (en) | 2019-12-26 |
US20240050317A1 (en) | 2024-02-15 |
US20230414452A1 (en) | 2023-12-28 |
WO2019246384A1 (en) | 2019-12-26 |
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