CN1217712C - 鼻传送装置 - Google Patents
鼻传送装置 Download PDFInfo
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- CN1217712C CN1217712C CN008045585A CN00804558A CN1217712C CN 1217712 C CN1217712 C CN 1217712C CN 008045585 A CN008045585 A CN 008045585A CN 00804558 A CN00804558 A CN 00804558A CN 1217712 C CN1217712 C CN 1217712C
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Abstract
一种用于将物质传送至受治疗者鼻道(1)特别是传送至鼻道后区的传送装置(20,22)及其方法,传送装置包括:闭合单元,用于使受治疗者口咽帆的闭合;以及传送单元,用于在驱动压力下传送带走物质的气流至受治疗者的一个鼻孔中,其中该驱动压力使气流围绕着鼻中隔后区流动并从受治疗者另一个鼻腔中流出,其中传送单元具有喷嘴(30,40,58,82,102,132),喷嘴包括出口和密封元件,气流在使用中通过该出口传送至上述一个鼻孔中,而且密封件用于密封上述一个鼻孔与出口隔离,从而在使用中防止气流通过上述一个鼻孔逸出。
Description
技术领域
本发明涉及一种将物质传送至受治疗者鼻道的传送装置及其方法,其中的物质特别是下列物质中的一种:液体(如悬浮液或溶液)、或含有药物的粉末(尤其是局部药物)、清洁剂或冲洗剂(最好为清洁剂结合的液体)。特别是,本发明涉及对鼻粘膜、鼻咽前区、鼻侧窦孔、耳咽管管孔、窦管、耳咽管、鼓室和鼻侧窦的药物传送及冲洗。
背景技术
参照图1,鼻道1由两个由鼻中隔分开的鼻腔构成,其中鼻道1包括很多的孔,诸如鼻侧窦孔3和管孔5、嗅觉细胞,并由鼻粘膜贴覆。鼻道1可以与鼻咽7、口腔9和下气道11互通,鼻道1与鼻咽7和口腔9的后区通过开启和关闭口咽帆13处于选择性地连通之中。通常也称作软腭的帆13,用实线表示为由于在口腔9中提供一定的正压而达到的关闭状态,例如通过口腔9呼气时的状态,并用虚线表示开启状态。
有很多需要治疗的鼻疾病。其中一种疾病是鼻炎症,尤其是鼻炎,可能是过敏性鼻炎或非过敏性鼻炎,并且通常与感染有关且妨碍了正常的鼻的功能。通过示例,鼻道的过敏性炎症和非过敏性炎症通常影响了10至20%的人群,其中最普通的症状就是鼻甲勃起组织的鼻充血、流泪、分泌水状粘液、打喷嚏和瘙痒。能够理解的是,鼻充血阻碍了鼻呼吸并促进了口呼吸,这导致打鼾而影响睡眠。令人担心的是,这类过敏性和非过敏性炎症疾病的发病率有所增加。其它鼻疾病包括鼻息肉,它是由于鼻侧窦、肥大性腺体、分泌性中耳炎(secretory otitis media)、窦疾病和减弱的嗅觉引起的。
在治疗某种鼻疾病时,药物的局部服用(topical administration)是优先考虑的,特别是在鼻粘膜是首要的病理通道的情况下,如在治疗或缓解鼻充血时。确实,局部服用在使系统服用时可能有的副作用最小化中是有利的。通常局部传送的药物包括减充血剂、抗组胺、色甘酸盐、类固醇和抗生素。
现在依赖药物来缓解鼻疾病症状的成人和儿童的数量日益增长。目前,在公知的消炎药中,局部类固醇已经表现出对鼻充血有作用。局部减充血剂也被推荐用于缓解鼻充血。还已经提议使用局部减充血剂、类固醇和抗微生物剂来治疗肥大性腺体和慢性分泌性中耳炎,尽管在某些程度上有一定争议。此外,药物的局部用法已经用于治疗或至少缓解鼻咽前区、鼻侧窦和耳咽管的炎症症状。
除了由药物缓解之外,用流体特别是盐溶液对鼻粘膜进行冲洗通常在实践中用于除去颗粒和分泌物,以及用于提高鼻粘膜的粘膜纤毛的活性。这些溶液可以与有效(active)药物结合使用。
此外,药物通过鼻道系统的不断传送,鼻道对于药品如激素、催产素和抗偏头痛复合物的系统传送提供了良好的服用路径,这是由于鼻粘膜的高速血流和较大局部积利于快速的系统吸收。
人们已经开发了多种传送体系,用于将物质传送至受治疗者的鼻道中。
传统上,喷雾瓶已被用于对受治疗者的鼻道传送含有药物的流体或冲洗的流体。然而,所传送的物质的分布,特别是对于鼻道后区的分布,不是理想的,尤其是在中度和严重鼻阻塞的情况下。这种不良分布通常因如医嘱在努力将物质传送至鼻道后区的过程中受治疗者通过鼻道呼气而进一步加重。实际上,在传送中,一定量的物质可被吸入肺中或被咽下,这在受治疗儿童中当药物是必须频繁服用的烈性药时是成问题的,如类固醇。此外,频繁地朝向鼻中隔进行喷雾,可能导致不理想的局部沉积。此外,喷雾瓶传送机构的机械动作可能引起冲洗和流血。
GB-A-408856公开了一种传送装置,其在一种使用模式中,允许两股带有药物的分离气流传送进受治疗者的两个分立鼻腔中。这种传送装置包括含有浸满了药物的海棉的腔室、连接到腔室上的套口、以及连接到腔室上的第一和第二喷嘴。在一种使用模式中,喷嘴配合进受治疗者各个鼻孔中,并且在通过喷嘴呼气时,带走药物的气流被吸进受治疗者的肺中。在另一种使用模式中,套口放进受治疗者的口中,并且在通过套口呼气时,带有药物的分离气流显然被驱赶进受治疗者的鼻腔中。
WO-A-98/53865公开了一种传送装置,它用于将含有药物的粉末传送至受治疗者一个鼻腔中的鼻粘膜上。该装置包括含有计量过剂量的粉末状药物的筒形部分。在使用中,筒形部分的端部分别设置在受治疗者的一个鼻腔的鼻孔中和口中,并且由受治疗者通过他或她的口呼气时,所呼出气体带走粉末状药物并将其传送进一个鼻腔中。在一个实施例中,筒形部分包括粉末状药物剂量的柔性上行区(upstream)部分。这种柔性部分的提供允许受治疗者在药物的上行点(a point upstream)关闭筒形部分,因而,在呼气时释放关闭的柔性部分时,带有药物的短暂突发性气流传送至一个鼻腔中。在另一个实施例中,位于鼻孔中的筒形部分的端部可以塑形,对将筒形部分定位在鼻孔中的一个位置起作用,该位置允许粉末状药物沉积在鼻粘膜中。
尽管这种传送装置在结构上是简单的,该装置仍不能实现有效地物质传送操作,特别是将含有药物的流体或粉末传送至鼻道后区,这是由于药物被单独传送至各个鼻腔中,并且流进和流出各鼻腔中的气体通过同一个开孔,即对应的鼻孔,其中各个鼻腔的关闭后区起到压力反射局部的作用,其使得所呼出气体在未曾完全到达各鼻腔后区之前从一个鼻孔回流。此外,在短暂突发性气体流入一个鼻腔中时,不可能的是实现持续受控的双向气体流经鼻腔,而这样却是将物质有效传送至鼻道后区所必须的。
对于任何要被有效传送至鼻道的物质来说,非常希望服用方法是有效且简单的。然而,致力于达到该目的也存在着问题。特别是,观察到的鼻炎症的病理变化使得物质如流体或粉末的用法错综复杂,特别是对于鼻道后区和鼻结构前区。事实上,作为鼻道中狭窄条状通道的复杂几何形状的结果,在鼻粘膜发炎和充血时这些通道变得局部闭合,难于向鼻道分散局部药物。
发明内容
因此,本发明的一个目的是提供一种用于获得物质最佳分散沉积的传送装置及其方法,尤其是对于局部药物在鼻道中的分散,特别是在鼻道后区的分散,并且更特别的是,在有腺体和管孔存在的鼻咽前区位置中的分散。
因而,本发明提供一种用于将物质传送至受治疗者鼻道中的鼻传送装置,包括:口呼气单元,用于使受治疗者的口咽帆闭合,所述口呼气单元包括套口,受治疗者在使用时通过它呼气以引起口咽帆闭合;以及传送单元,用于在驱动压力下传送带有物质至受治疗者其中一个鼻孔中,该驱动压力能使得气流围绕受治疗者的鼻中隔后边流动并从另一个鼻孔流出,其中传送单元具有喷嘴,该喷嘴包括出口及密封件,气流在使用中通过该出口传送至所述一个鼻孔;密封件用于在所述出口和所述一个鼻孔之间提供液密密封。
在一个实施例中,物质为干燥粉末。
在另一个实施例中,物质为液滴。
优选的是,物质的颗粒尺寸分布主要在大约1至10微米的范围内。
在一个实施例中,该物质含有药物,特别是用于治疗鼻疾病的药物。在优选实施例中,物质的颗粒分布可以为大颗粒的几分之一,通常在大约10至30微米的范围内,并且优选在大约20至30微米的范围内。
在其它实施例中,物质可以为如粉末状或液态的清洁剂用于清洁鼻道,或为最好含有清洁剂的流体用于冲洗鼻道。通过示例,传送装置可以用于对鼻道使用盐溶液或其它溶液来除去颗粒和分泌物,特别是从鼻道后区除去颗粒和分泌物,这样产生的溶液可被分析用于诊断或研究目的。在优选实施例中,清洁剂或冲洗剂的颗粒尺寸分布可以为大颗粒的几分之一,特别是与颗粒的机械作用成比例。
本发明还提供了一种将物质传送至受治疗者鼻道的方法,其包括如下步骤:将受治疗者一个鼻孔密封与传送装置的出口隔绝,这样防止气体流经所述一个鼻孔逸出;关闭受治疗者的口咽帆;并且在压力下传送带有物质的气体流经出口,其中压力能使气体围绕受治疗者的鼻中隔后线流动并从另一个鼻孔流出。
在一个实施例中,帆的闭合通过使用下压帆来关闭帆的仪器或者使用塞子来临时关闭帆后面的鼻道和口腔之间的开口而直接完成。
在优选实施例中,帆的闭合通过在口腔中产生正压或者更适当地在呼气时获得的口腔和鼻道之间的正压差而间接完成。
优选的是,帆在物质开始传送至鼻道的同时闭合。
在优选实施例中,帆的闭合是由受治疗者对气流阻挡件进行呼气而自动完成的,其中气流阻挡件可以连接至夹在受治疗者嘴唇间的沟道。气流阻挡件可以构造成提供所需的口内正压。
已经确定的是,每分钟大约1至20升、特别是每分钟大约3至15升的流速,可以容易地由受治疗者获得,并且相当恒定的气流根据流速可以保持达20秒。对于一些治疗方式,重要的是,为了能够使物质穿透到鼻道的较遥远的部位,较高流速的稳定流动保持在数秒的时间段中,优选为3至10秒。
在一个实施例中,受治疗者呼出的气流用于给机构以动力,该机构将物质分散进一定量的空气中,并且将所分散的物质传送进鼻道中。
优选的是,该机构安排成使得物质在帆已经闭合之后或与帆闭合同时传送进鼻道中。在这方面,可以理解的是,流经鼻腔的双向气流只在帆闭合时是可能的,并且任何在帆闭合之前传送的物质将不理想地传送至下气道或内脏。
优选的是,物质释放进鼻道中是由呼气产生的气流触发的。
在优选实施例中,压敏阀用于在已经形成预定流速时触发物质释放。应该理解的是,其中传送物质的气体流速的控制是重要的,因为该流速与物质的颗粒尺寸分布是确定颗粒沉积效率的重要因素。
在优选实施例中,压敏阀直到受治疗者保持了预定流速才开启,并且可以在流速下降到低于预定流速时关闭以便停止物质的传送。
在优选实施例中,其中药物是在驱动气体中传送的,压敏阀开启的计时或/和期限以及释放的剂量被小心的控制以确保标准化的剂量。
在一个实施例中,其中物质传送进腔室中,并且气流(在一个实施例中是呼气气流)用于促使计量过剂量的物质混合,并且气流的传送可以延长来灌注鼻道,是由于这种延长的灌注不影响所传送的剂量。由手动弹簧、加压气体或类似装置给予动力的机械装置可用于提供驱动气体。
与使用的系统无关,流动特性可以优化,以提高物质的沉积和舒适指数,诸如避免容易触发回吸(withdrawal reflexes)的突然开始。
优选的是,计量过剂量的物质由计量装置发散到传送腔室中。该剂量装置可构造成允许物质逐渐释放。这种逐渐释放能够使物质更好地由气流带走,并由此改善对鼻道所有通气部位的传送,特别是在对侧鼻腔中。
在优选实施例中,由受治疗者关闭帆产生的呼气气流提供了用于带走物质的气流并且提供了双向气流。该结构是有利的,在于不需形成分离的驱动气流。
优选的是,喷嘴构造成延伸进一个鼻腔中大约1厘米,以便扩大阀区,该阀区位于鼻腔中大约2至3厘米通常为流动限制区,并且减少在鼻炎症的情况中可能较高的阻力。
喷嘴的形状可以适合于特殊需求。例如,喷嘴的内部形状可被优化,以促进涡旋并且达到物质的最佳分散。
喷嘴可以包括紧密配合的鼻橄榄体(olive),其可以辅助合适的生理气流的产生。橄榄体是可拆卸的,这样允许相同或不同尺寸的橄榄体配合。在严重鼻塞的情况下,鼻橄榄体可以引入另一个鼻孔中以降低阻力并促进其中气体流动。
如上所述,每分钟至少20升的气流可以容易地由传送装置实现。通过提供足够高速的气流,复杂鼻道的所有部位或至少一个较大部位可以被物质穿过。在一个实施例中,传送装置可以包括用于指示气流量的指示器。
鼻中隔后面的后通道和开口的尺寸几乎总是大于气流阻挡件的开口。因此,只在鼻孔完全阻塞的极稀少的情况下,鼻道后区的压力将接近口腔中的正压并且危及帆的闭合。在严重鼻塞的情况下,将喷嘴插入堵塞的鼻孔中可以降低阻力并能够成功冲洗。
已经在一个方向上冲洗鼻道之后,在另一个鼻孔中重复相同程序。用这种方法,两个鼻腔在两个方向上冲洗。这就是该装置的独一无二的特点。该实施例确保达到鼻粘膜的所有部位上改进的物质分散,并且特别是使用现有技术难于到达的后区。
在优选实施例中,其中该物质是固态,诸如粉末,如果高水分含量对于服用该固体产生了问题,则可以使用过滤器。
该物质可以是单一的复合物或者复合物的混合物,其中复合物可以是任何合适形态,如粉末形态、溶液或悬浮液。
该物质可以是任何合适的用于传送至人体或某些情况下传送至动物的物质。该物质可以用于传送在鼻道任何部位或者在任何周围组织或器官中起作用。另外,物质可以用于传送到远离鼻道的区域起作用。
优选的是,物质用于传到鼻道的任何部位或者在任何周围组织或器官中连续起作用。
该物质可以具有有益的医疗作用,其可以包括诊断作用、治疗作用、预防作用、以及清洁作用,如除去颗粒、结痂、分泌物、碎屑,等等。优选的是,该物质具有治疗作用。
优选的是,该物质是药品。该药品可以与任何合适的载体、稀释剂、赋形剂或佐剂混合。
优选的是,药品用于治疗上述提及的疾病中任一种或多种。通过示例,药品可用于治疗任何过敏性和非过敏性炎症疾病。
用于服用的一般药品包括,但不限于,类固醇、抗组胺、色甘酸盐、抗过敏性药品、消炎药品、抗白三烯、泌乳促进剂(如催产素)和抗偏头痛药品。
通过实现更佳的传送,本发明的传送装置提高了在治疗上呼吸道病理(诸如肥大性腺体和慢性分泌性中耳炎)中的局部药品的作用。
除了药品之外,该装置还可以用于用盐溶液或其它溶液冲洗或清洁鼻道,优选用含有油或草药的溶液。
本发明的装置可以适合于特殊需求。例如,很容易结合球体或弹跳方式以用于提供流速半量(semi-quantitative)指示,并且提高可接受性且易于小儿服用。
只有在极少的鼻阻力太高甚至在努力扩大鼻腔后仍不能实现气体流经鼻道的情况下,气流吹进受到影响。在这些情况中,用减充血剂进行预处理是必须的。
传送装置还可以用作收集来源于鼻粘膜的介质和细胞的鼻灌洗装置,例如,用于诊断分析或研究目的。在该方面,介质和细胞在鼻道已经暴露于合适溶液如盐溶液之后排放到合适的收集器皿中一段充分的时间,以确保介质和细胞充分转移到溶液中。装置的这种用法要求独立于呼气气流的气流作为用于冲洗鼻道的气流。为了这种灌洗目的,使用呼气气流是不可能的,这是由于下呼吸道可能含有介质、分泌物和源自于下呼吸道的细胞,它们将污染鼻子样本。对于这种特殊用途,如所指示的,从鼻孔的出口排出的流体可收集在器皿中。或者,从鼻孔出口排出的流体可吸收到过滤器上用于直接分析或稍后分析。实际上,这种过滤器或类似物甚至可以产生几乎立刻的对于某种有机物的检测结果,这些有机物如细菌、病毒或介质。
由于数个原因,本发明的传送装置是有利的。
值得注意的是,传送装置提供了一种极为简单有效的传送物质至鼻道的装置,其中的物质如药品、盐溶液等等。在该方面,装置使用具有几个可动部件的极简单的技术,该装置的大批量生产较为低廉。此外,本发明的装置可以作成一次性形式,因此避免了传送物质时需要包括一些防腐剂。
本发明还消除了对于现有技术装置相关的灌注或喷雾方法的需求。然而,对于一些应用场合,进行持续灌注或喷雾操作仍是理想的。
本发明的传送装置的优点还在于:由于在使用中,喷嘴和一个鼻孔之间的密封确保了复杂鼻道的延长穿透能力、双向气流流经鼻腔以及物质在对侧鼻道中的沉积。
根据本发明,帆的闭合通常会保持。传送的气流进入一个鼻腔中,通过鼻中隔后区上方,在鼻中隔后区发生180度转弯,并且由另一个鼻孔流出。这种气流方向的改变导致物质特别是药品较好的沉积至鼻甲和鼻粘膜的后区。
此外,由于解剖学位置和窦孔的定向,物质(通常为药品)的双向沉积以及冲洗还将较好地到达所有窦孔中,这可以提高窦的通气能力和导液能力,而导液能力对于治疗窦炎和鼻粘膜的频繁伴生炎症是必须的。在该方面,筛骨窦和蝶骨窦的孔和管位于鼻道的后区,并且覆盖动脉圆锥、罩住上颌骨、前和后筛骨孔的钩状突起向后倾斜。此外,所用的驱动正压将增加药品在窦孔、引向窦的窦管处的沉积,甚至在窦自身中沉积。
此外,鼻中隔后面的气流180度转向特别增加了物质在存在有腺体的鼻咽根部及靠近连接鼻咽和中耳耳咽管管孔的位置附近的沉积。通过示例,类固醇已经呈现出能减小通常发现于受治疗儿童中的肥大性腺体的尺寸,并且对分泌性中耳炎具有积极效果。靠近管孔的局部减充血剂的沉积还可以更有效地减轻耳咽管的充血,并且缓解中耳内的负压,其中负压伴随着鼻炎产生并使受治疗儿童更易感染分泌性中耳炎和相应发生听力下降。对扩大腺体进行外科手术在儿童中常见,并且本发明的改进医疗方法应该减少外科手术的必要性。
另一个优点在于,可能有过剩物质,即,未沉积的物质,将从对侧鼻孔中排出(如果需要的话可以在鼻孔处收集),并且和许多其它传送技术的情况一样,随后不连续进入口腔并且向下进入内脏。用该方法,将减少不舒适感,且更重要的是,将减少当物质是药物时对物质的不理想系统暴露。
而且,与用于鼻道冲洗和灌注的现有技术相比,本发明可以更有效地实现用盐溶液或其它溶液的冲洗,并且较少溢出且无不适感。
另外,本发明提供了用溶液如盐溶液和其它油类简单且舒适地冲洗鼻粘膜,以除去来自鼻粘膜的分泌物并促进粘膜纤毛的功能。
更进一步的是,本发明提供了鼻粘膜灌洗的简单有效的方法,诸如收集和诊断粘膜病种,如细菌、病毒、细胞组分和炎症介质。
再进一步的是,鼻粘膜暴露于正压中,特别是动力学正压,将开启狭窄的有时被阻塞的鼻道的部位,而不是引起可能在鼻吸气和呼气过程中发生的动力学萎陷(collapse)。动力学正压至少为5厘米水柱,优选至少为50厘米水柱,更优选的是至少100厘米水柱,更优选的还可是至少200厘米水柱,最优选的是400厘米水柱,最优选的还可是500厘米水柱。本发明所达到的动力学正压可与由瓦尔萨尔瓦过程产生的鼻道中无流动的静力学压力形成对照。
此外,温暖湿润的气流比室内气流或室外气流更易于承受并不太引起冲洗,特别是在寒冷的气候下。
当物质是干燥粉末时,所呼出气体的水分在一些情况下可能导致粉末结块。当然,这将取决于粉末的性质和装置的构造,特别是分散腔室的构造。为了缓解上述特殊问题,可以改变粉末的局部性质,或者装置可包括设置在分散腔室上行区的水分吸收元件,通常是含有干燥剂,如硅。在优选实施例中,水分吸收元件可以设置成作为气流阻挡件的过滤器。
在优选实施例中,为了确保粉末的结块不妨碍温暖湿润的呼出气体直接吹入法的使用,传送装置包括转移装置,其产生干燥气体的气流,诸如大气,作为对鼻道的传送气流。这种实质上可能是机械的转移装置,利用所呼出气体的能量在所需流速下(如果需要)驱动室内大气气流,将物质分散在传送的气流中。在该实施例中,结块现象将被防止,或者至少降低到和目前的干燥粉末吸入器呈现的水平相同。
如果需要,传送至鼻道的物质分布可以用标准技术研究。通过示例,可以使用声学鼻腔计或者有色彩的流体。所传送物质的分布甚至可由视频内窥镜确定。此外,或者另一种方案是,分布研究还可以通过采用合适的放射性材料并流经鼻腔中的通道而完成。这些研究的结果可用于使流速、装置的形状和尺寸特别是喷嘴的几何形状以及物质的颗粒尺寸分布优化。这些研究的结果甚至可用于受治疗者可接受程度的优化。
如已经指出的,传送装置可以包括用于指示已经获得所需正压的球体或类似的弹跳装置,其中球体或弹跳装置可以提高那些不愿意使用该装置的幼儿的顺从程度。
另一种方案是,特别是对于幼儿,吸入的气流可以由另一个人如父母或者甚至利用泵等类似物的呼气气流提供,而通过膨胀球体或弹跳装置使儿童口腔中产生所需正压。
附图说明
本发明的优选实施例在下文将参照附图只示例性地进行描述,附图中:
图1示意性地说明了人体的上呼吸道的解剖学结构;
图2示意性地说明了本发明第一实施例的传送装置;
图3示意性地说明了本发明第二实施例的传送装置;
图4示意性地说明了本发明第三实施例的传送装置;
图5示意性地说明了本发明上述第一至第三实施例的变型的传送装置;
图6示意性地说明了本发明第四实施例的传送装置;
图7示意性地说明了本发明第五实施例的传送装置;
图8示意性地说明了本发明第六实施例的传送装置;
图9示意性地说明了本发明第七实施例的传送装置。
具体实施例方式
图2说明了本发明第一实施例的传送装置。
该传送装置包括口呼气单元20和物质传送单元22。在该实施例中,口呼气单元20和传送单元22设置成分离的部件,但是还可以例如利用VelcroTM固定器可拆卸地接合,或例如利用螺纹和/或铆钉连接,或甚至一体地形成。
口呼气单元20包括筒形部分24和连接到筒形部分24一端的套口26。套口26在使用中夹在使用者的嘴唇间,该套口独立于筒形部分24形成而允许替换,但另一种方案是一体形成的。在该实施例中,套口26是弹卡配合在筒形部分24上的,但是同样可用螺纹配合。筒形部分24包括气流阻挡件28,在该实施例中是一固定挡板,其构造成对穿过其中的呼气提供充分阻力,从而由受治疗者产生的呼气引起受治疗者口腔中产生正压以及在受治疗者呼气时使帆(velum)闭合。在备选实施例中,气流阻挡件可以是一移动元件,诸如偏置折板、弹性隔膜或阻尼轮。
传送单元22包括:喷嘴30,在该实施例中,它是由弹性材料如聚合物材料制成的,用于在受治疗者的一个鼻孔中提供密封配合;药物供给单元32,用于提供在预定压力下带走药物的气流,其中该压力足以在药物传送进受治疗者的一个鼻腔时打开超过鼻中隔后边的流动路径;以及筒形部分34,其连接着喷嘴30和药物供给单元32。在优选实施例中,喷嘴30可包括外橄榄体,或者成型使得插入了喷嘴30的鼻腔前区扩大。在特别优选实施例中,喷嘴30可以成型为例如包括涡旋产生凸起(whirl-inducingprojections),以为排出的气流最佳流动方式和颗粒尺寸分布。喷嘴30独立于筒形部分34形成而允许替换,但是也可以是一体形成的。在该实施例中,喷嘴30弹卡配合在筒形部分34上,但是也可用螺纹配合。药物供给单元32可以包括气雾喷雾发生器,用于产生含有药物的液滴气雾喷雾(诸如由加压计量过剂量的吸入器提供)或者包括加压的气体源,用于带走其中含有药物的干燥粉末的计量过的剂量,其中粉末还可以加载在筒形部分34的腔室中。
在使用中,受治疗者用他或她的嘴唇夹住套口26,并将喷嘴30配合在他或她的一个鼻孔中。接着,该受治疗者通过套口26呼气,所呼出气体的流动受到筒形部分24中气流阻挡件28的阻挡,诸如在受治疗者口腔中产生正压,其中该正压能够在帆之中产生压差,足以使受治疗者帆闭合。申请人已经确定了口腔和鼻道之间的大约5厘米水柱的正压差是保持帆处于关闭状态所必需的。申请人还确定了的是,受治疗者应该能够保持每分钟3至30升的流速大约1至20秒,每分钟大约10至20升的流速和大约2至5秒的传送时间被认为是最佳的。帆闭合之后,接着药物供给单元32启动,将带有药物的气流传送通过喷嘴30并进入受治疗者的鼻道中。如上所述,该气流处于这样的压力之下,该压力能够打开互通路径,使之超过鼻中隔的后区,从而气流流经一个鼻腔、围绕着鼻中隔的后边,事实上,转过180度的角度从另一个鼻腔中出来。而且,如已描述的,这种双向流动强化了药物在鼻道后区中的沉积效果。
在一个变型例中,传送单元22可以省略药物供给单元32,代之以一种计量过剂量的干燥粉末被加载到筒形部分34腔室中,其中传送气流是由另一个人如受治疗儿童的父母将气流吹进筒形部分34的末端完成的。
图3说明了本发明第二实施例的传送装置。
该传送装置包括:口呼气单元20和上述第一实施例的传送单元22,以及出气单元36,它用于配合到装了传送单元22的受治疗者另一个鼻孔。
出气单元36包括筒形部分38和喷嘴40,它们在该实施例中是由弹性材料如聚合物材料制成的,并且连接到筒形部分38的一端上,用于形成受治疗者另一个鼻孔的密封配合。喷嘴40独立于筒形部分38形成而允许替换,但也可以是一体形成的。在该实施例中,喷嘴40是弹卡配合在筒形部分38上,但是同样可用螺纹配合。由于具有传送单元22的喷嘴30,在优选实施例中,喷嘴30可包括外橄榄体,或者成型使得插入了喷嘴30的另一个鼻腔前区扩大。筒形部分38包括气流阻挡件41,在该实施例中是一挡板,其构造成对穿过其中的呼气提供充分的流动阻力,从而引起鼻道中产生动力学正压。在优选实施例中,气流阻挡件41是可调节的,以允许调节阻力水平并由此控制鼻道中的动力学压力。在备选实施例中,该气流阻挡件41可以是一可动元件,诸如偏置折板、弹性隔膜或阻尼轮。
在优选实施例中,出气单元36包括指示器,用于在其上游(鼻道中)获得预定正压时提供至少一个可视或可听信号。优选的是,指示器具有哨子。这样,为受治疗者提供了装置正确使用的正反馈。
该实施例传送装置的使用和上述第一实施例的相同。然而,如上所述,通过在受治疗者鼻孔出气端处的出气单元36中设置气流阻挡件41,可以将动力学正压保持在鼻道中。该正压利于鼻道中的各孔及相关的各管膨胀,诸如窦孔和管孔、窦管和耳咽管,从而促进药物的传送。此外,该正压作用为改善这种沉积经常阻塞管孔的腺体、鼻息肉常在处的中道,以及对嗅觉细胞的裂口等处的沉积。
图4说明了本发明第三实施例的传送装置。
该传送装置非常类似于上述第二实施例的传送装置,并且为避免不必要的说明重复,只有差异之处详细说明,相同的部件使用相同的附图标记。该传送装置不同之处仅在于还包括:压力传感器43,在该实施例中是压敏簧片或隔膜,它位于药物供给单元32的下行区的传送单元22的筒形部分34;以及连接到传感器43和药物供给单元32上的控制单元44。
控制单元44构造成控制由药物供给单元32提供的传送气体的流速,以便在不管鼻充血程度的情况下使颗粒沉积在鼻道中的效率最佳。如前所述,通过保持鼻道中的最佳流速,含有药物颗粒的沉积效率(称作颗粒沉积效率)增加。通常,如果需要每分钟大约15升的流速来使颗粒沉积效率最大化,则在充血的鼻道中可能需要每分钟10升的较低流速,而在未阻塞的鼻道中可能需要每分钟20升的较高流速。
该传送装置的工作方法和上述第二实施例的相同。
图5说明了用于上述实施例传送装置的改型口呼气单元20。
该改型的口呼气单元20不同之处在于,筒形部分24在气流阻挡件28上行区包括一个侧向开口45,并且还具有作为指示器的连接到侧向开口45的可充气图形46,该图形46在充气时呈现在受治疗者视野中的显著位置。在图4中,图形46示出是充气的。通过提供这样一种显示部件,受治疗者特别是受治疗儿童的适应能力应该有所提高。口呼气单元20还包括充气管道48,其允许图形46进一步由另一个人充气,一般是受治疗儿童的父母或泵。在另一个实施例中,代之以可充气的,图形46可以为任何类型,它在受治疗者呼气时进入显著位置,一般是机械或电操作的图形。在优选实施例中,图形46可以构造成能够在受治疗者获得最佳呼气流速时充气。用该方法,图形46用作指示器。
本实施例传送装置的使用和上述第一实施例的相同。然而,在通过套口26呼气时,所产生的压力使得图形46充气并呈现在受治疗者视野中的显著位置。图形46的这种外观作为充气图形46的有趣元素特别能唤起受治疗儿童的兴趣,这可以缓解一些不必要的焦虑。
图6说明了本发明第四实施例的传送装置。
该传送装置包括:腔室50,其包括入口52和出口54;连接到入口52上的套口56;以及连接到出口54上的喷嘴58。喷嘴58构造成在受治疗者一个鼻孔中形成密封配合。腔室50包括:气流阻挡件60,在该实施例中是多个挡板;以及在气流阻挡件60下行区的药物接收室62,用于容纳计量过剂量的含有药物的干燥粉末,以传送至受治疗者鼻道中。在该实施例中,喷嘴58由弹性材料如聚合物材料制成。在优选实施例中,该腔室50可以包括干燥剂。在优选实施例中,气流阻挡件60可以由水分吸收过滤器形成。
在使用中,受治疗者用他或她的嘴唇夹住套口56并且将喷嘴58配合进他或她的一个鼻孔中。接着,该受治疗者通过套口56呼气,其中所呼出气体的流动受到腔室50中的气流阻挡件60以及鼻道阻力的阻挡,这样在受治疗者口腔中产生正压而导致帆闭合。所呼出气体,在经过气流阻挡件60之后,接着带走药物接收室62中的粉末状药物,并且该带有药物的气流接着通过喷嘴58进入受治疗者的鼻道中。进入鼻道的呼出的气体处于这样的压力下,该压力足以开启超过鼻中隔后区的互通路径,从而气流流经一个鼻腔,围绕着鼻中隔的后区,实际上转向通过180度的角度并从另一个鼻腔中出来。而且,如已经描述的,这种双向流动强化了药物在鼻道后区中的沉积。
在优选实施例中,该传送装置包括优选位于套口56中的压力触发阀,其构造成仅在由受治疗者呼气产生预定正压的时候开启,该预定正压一般为大约10厘米水柱的正压。有利的是,这种构造避免了在帆处于开启状态下药物传送至鼻道的可能性,并且由此降低了药物不理想地沉积在鼻道外部的风险性。
在另一个优选实施例中,与上述第三实施例类似,传送装置可以包括出气单元,提供用于受治疗者另一个鼻孔下行区的气流阻挡件,这样保持了鼻道中的动力学正压。
图7说明了本发明第五实施例的传送装置。
该传送装置包括:口呼气单元70,受治疗者通过它呼气以闭合他或她的帆;以及药物传送单元72,用于向受治疗者的鼻道提供带有药物的气流。
口呼气单元70包括筒形部分74和连接到筒形部分74一端的套口76。夹在受治疗者嘴唇间的套口76独立于筒形部分74形成而允许替换,但是也可以一体形成。在该实施例中,套口76弹卡配合在筒形部分74上,但是同样可用螺纹配合。筒形部分74包括气流阻挡件78,在该实施例中是齿轮,其构造成在受治疗者呼气时转动并且对呼气气流提供充分阻力,从而在受治疗者口腔中产生正压,该正压足以保持口腔和鼻道之间所需的正压差,并由此保持帆处于关闭状态。
传送单元72包括筒形部分80和连接到筒形部分80的一端上的喷嘴82,在该实施例中是由弹性材料如聚合物材料形成的,用于在受治疗者一个鼻孔中形成密封配合。喷嘴82独立于筒形部分80形成而允许替换,但是另一种方案是一体形成。在该实施例中,喷嘴82弹卡配合在筒形部分74上,但是同样可用螺纹配合。在优选实施例中,喷嘴82可以包括外橄榄体或者被塑形成导致插有喷嘴82的鼻腔后区扩大。在特别优选实施例中,喷嘴82可被塑形,例如通过包括涡旋产生凸起,以提供给排出的气流最佳流动方式和颗粒尺寸分布。筒形部分80包括连接到口呼气单元70筒形部分74中的齿轮78上的叶轮84,从而随着齿轮78转动而转动,以将气体抽进筒形部分80并在压力下产生通过它的气流,该压力足以在传送进受治疗者鼻腔之一时开启超过鼻中隔后区的互通路径。
该传送单元72还包括分散单元86,用于将计量过剂量的含有药物的干燥粉末分散到叶轮84上行区的筒形部分80中,在该实施例中,分散单元86手动启动,将计量过剂量的含有药物的粉末提供到筒形部分80中,但是另一种方案是构造成由齿轮78驱动,从而不需要在受治疗者部位上任何手动干涉。
在使用中,受治疗者在他或她的嘴唇间夹住套口76并且将喷嘴82配合进他或她的一个鼻孔中。接着,该受治疗者通过套口76呼气,其中所呼出气体的流动受到齿轮78的阻挡,这样在受治疗者口腔中产生足以导致受治疗者的帆闭合的正压。所呼出气体引起齿轮78转动,而齿轮78的转动又引起叶轮84的转动,而叶轮84的转动产生了通过筒形部分80的气流,该气流带有计量过剂量的含有药物的干燥粉末,并将该粉末通过喷嘴82传送至受治疗者的鼻道。如上所述,该气流处于足以开启超过鼻中隔后边的互通路径的压力之下,从而气流流过一个鼻腔,围绕着鼻中隔的后区,实际上转向180度并从另一个鼻腔中出来。而且,如已经描述的,这种双向流动大大强化了药物在鼻道后区中的沉积。
在优选实施例中,齿轮78构造成使得阻止其转动,直到已经达到预定流速为止,其中该流速足以确保由叶轮84产生的带走的气流最佳。有利的是,这种构造确保了最佳的颗粒沉积效率并且避免了在帆处于开启状态下药物传送至鼻道的可能性,并且由此降低了药物不理想地沉积在鼻道外部的风险性。
图8说明了本发明第六实施例的传送装置。
该传送装置包括:用于罩住泡罩包装件92的外壳90,其中包括有多个泡罩94,各泡罩含有带有药物的粉末;以及在开启时与其中一个泡罩94互通的筒形部分96,该筒形部分96的一端形成在使用中夹在受治疗者嘴唇间的套口98。筒形部分96包括可动地设置在常闭的第一位置和开启的第二位置之间的元件100。在该实施例中,元件100为旋转地安装在螺纹轴上并且通常由压缩弹簧垂直偏压至关闭位置的推进器或类似物。该元件100构造成既作为气流阻挡件又作为阀。在该实施例中,该元件100构造成通过克服压缩弹簧的偏压沿着螺纹轴转动而移动到药物释放开启位置,其中粉末只在呼气流速超过预定流速时才可由气流带走。流速与驱动压力成反比的函数关系,该流速优选在范围大约每分钟5至20升之间,在该流速下含有药物的粉末由气流带走,而驱动压力自身是上述鼻阻力的函数。如所可以理解的,有利的是,这种构造在最佳流速下在释放含有药物的粉末中提供了最佳颗粒沉积效率,并且避免了在帆处于开启状态下药物被传送至鼻道的可能性。
该传送装置还包括连接到筒形部分96的元件100下行区另一端上的喷嘴102,在该实施例中是由弹性材料诸如聚合物材料制成的,用于形成在受治疗者一个鼻孔中的密封配合。该喷嘴102独立于筒形部分96形成而允许替换,但是另一种方案是两者可以一体形成。在该实施例中,喷嘴102弹卡配合在筒形部分96上,但是同样也可以螺纹配合。在优选实施例中,喷嘴102可包括外橄榄体或者塑形成使得插入喷嘴102的鼻腔后区扩大。在特别优选实施例中,喷嘴102可以塑形,例如通过包括涡旋产生凸起,以提供给排出的气流最佳流动方式和颗粒尺寸分布。
传送装置还包括泡罩开启机构104,用于开启泡罩94与筒形部分96互通。在该实施例中,在传送之前,泡罩开启机构104由受治疗者手动开启。
在使用中,受治疗者在他或她的嘴唇间夹住套口98并将喷嘴102配合进他或她的一个鼻孔中。接着,该受治疗者通过套口98呼气,其中所呼出气体的流动受到元件100的阻挡,直到已经达到预定流速。一旦已经达到预定流速,而且在该流速下帆处于关闭状态,则元件100处于开启状态,并且呼出的气流带走泡罩94中的粉末状药物并将其传送通过喷嘴102至鼻道中。该气流的驱动压力处于这样的压力下,该压力足以保持互通路径超过鼻中隔后区,使得气流流经一个鼻腔,围绕着鼻中隔的后区,事实上,转过180度的角度从另一个鼻腔中出来。而且,如已描述的,这种双向流动大大强化了药物在鼻道后区中的沉积效果。
在优选实施例中,该传送装置包括泡罩包装改进机构,它由套口98的运动而被控制,用于转动泡罩包装元件92,从而另一个未使用的泡罩94位于传送位置。在特别优选实施例中,泡罩包装改进机构可以结合到泡罩开启机构104上,以自动地开启泡罩94,并由此避免了对在受治疗者部位上任何手动干涉的需要。
在一个变型例中,类似于图3所述的第一实施例的上述变型。传送装置可包括出气单元,提供形成受治疗者另一个鼻孔下行区的气流阻挡件,这样保持了鼻道中的动力学正压。
在另一个变型例中,泡罩包装元件92可以省略代之以外壳90,该外壳90设置有腔室,该腔室与筒形部分96互通,并且腔室中可以装载有计量过剂量的含有药物的干燥粉末。由于这种构造,腔室中的粉末在元件100驱动至第二位置时被带走,并且泡罩包装改进机构构造成在其工作时计量进入腔室中的含有药物粉末的剂量。
如可理解的,实质上,本发明在广义上可基于任何干燥粉末吸入器,诸如AstraZeneca PLC生产的TurbuhalerTM、由Schering AG生产的Glaxo PLC或TwisthalerTM,其中常用的套口由喷嘴替代,而套口设置成与吸入器的气流入口互通,从而利用受治疗者呼出的气体作为传送气体。
图9说明了本发明第七实施例的传送装置。
该传送装置包括外壳110和延伸穿过外壳110的筒形部分112,其一端形成了在使用中夹在受治疗者嘴唇间的套口114。
筒形部分112包括可动地设置在常闭第一位置和触发第二位置之间的元件116。在该实施例中,元件116为旋转地安装在螺纹轴上并且由压缩弹簧垂直偏压至关闭位置的推进器或类似物。该元件116构造成既作为气流阻挡件、阀,又作为将气雾传送喷雾进筒形部分112中的触发器。在该实施例中,该元件116构造成通过克服压缩弹簧的偏压沿着螺纹轴转动而移动到药物释放开启位置,其中粉末只在呼气流速超过预定流速时才可由气流带走。流速与驱动压力成反比的函数关系,该流速优选在范围大约每分钟5至20升之间,在该流速下药物被带走,而驱动压力自身是上述鼻阻力的函数。如所可以理解的,有利的是,这种构造在最佳流速下在释放药物中提供了最佳颗粒沉积效率,并且避免了在帆处于开启状态下药物被传送至鼻道的可能性。
筒形部分112还包括喷头部件117,用于沿其纵轴提供穿过筒形部分112的气雾喷雾。如在下文将要详细描述的,喷头部件117容纳气雾罐120的阀杆122。
传送装置还包括公知的气雾罐120,其用于传送含有药物如悬浮液或溶液的计量过体积的挥发剂,优选为HFA挥发剂或类似物。气雾罐120包括:主体121,其在压力下含有一定量的含有药物的挥发剂;阀杆122,含有药物的挥发剂在使用中通相对主体121的运动经该阀杆传送;以及计量阀124,用于在阀杆122运动时计量到阀杆122的预定量的含有药物的挥发剂。
传送装置还包括:用于相对移动气雾罐120的主体121及阀杆122的触发机构126,用于实现含有药物的计量过的挥发剂传送通过喷头部件117。在该实施例中,触发机构126包括:用于以致动力承载主体121的弹性元件128;以及连接到可动元件116上的杠杆组件130,使得由弹性元件128提供的致动力在可动元件116从关闭位置运动到触发位置时释放。
传送装置还包括喷嘴132,在该实施例中是由弹性材料如聚合物材料制成的,用于在受治疗者一个鼻孔中形成密封配合,其连接到可动元件116下行区筒形部分112另一端上。喷嘴132独立于筒形部分112形成而允许替换,但另一种方案是一体形成。在该实施例中,喷嘴132是弹卡配合在筒形部分112上的,但是同样可用螺纹配合。在优选实施例中,喷嘴132可以包括外橄榄体,或者成型使得插入了喷嘴132的鼻腔前区扩大。在特别优选实施例中,喷嘴132可以成型为例如包括涡旋产生凸起,以提供给排出的气流最佳流动方式和颗粒尺寸分布。
在使用中,受治疗者发动触发机构126、在他或她的嘴唇间夹住套口114并将喷嘴132配合进他或她的一个鼻孔中。接着,该受治疗者通过套口114呼气,其中所呼出气体的流动受到可动元件116的阻挡,直到已经达到预定的流速。一旦已经达到预定的流速,而且在该流速下帆处于关闭状态,则元件116处于开启状态,触发杠杆组件130的运动以及气罐120的主体121与阀杆122之间的相对运动将计量过的含有药物的挥发剂传送至喷头部件117,以产生含有药物的液滴的气雾喷雾通过喷嘴132至鼻道。这种气雾流动处于足以保持互通路径超过鼻中隔后区,使得气流流经一个鼻腔,围绕鼻中隔的后区,转过180度的角度从另一个鼻腔中出来。而且,如已描述的,这种双向流动强化了药物在鼻腔后区中的沉积效果。
如可理解的,实质上,本发明在广义上可基于任何呼吸致动的加压计量过剂量的吸入器,其中常用的套口由喷嘴替代,而套口设置成与吸入器的气流入口互通,从而触发触发机构并利用受治疗者呼出的气体作为传送气体。
最后,可以理解的是,尽管本发明以其优选实施例进行了描述,但是在不脱离所附权利要求书限定的本发明范围的前提下,可以以多种不同方式进行改型。
Claims (25)
1.一种用于将物质传送至受治疗者鼻道中的鼻传送装置,包括:
口呼气单元,用于使受治疗者的口咽帆闭合,所述口呼气单元包括套口,受治疗者在使用时通过它呼气以引起口咽帆闭合;以及
传送单元,用于在驱动压力下传送物质至受治疗者其中一个鼻孔中,其中驱动压力能使气流围绕受治疗者的鼻中隔后边流动并从另一个鼻孔中流出,
其中传送单元具有喷嘴,该喷嘴包括出口及密封件,通过该出口物质在使用中传送至所述一个鼻孔,密封件用于提供所述出口与所述一个鼻孔之间的液密密封。
2.如权利要求1所述的鼻传送装置,其特征在于,所述口呼气单元包括连接到套口上用于对呼出的气流提供流动阻力的气流阻挡件。
3.如权利要求2所述的鼻传送装置,其特征在于,所述气流阻挡件构造成在受治疗者呼气时,保持上行位置和下行位置之间至少大约5厘米水柱的正压差。
4.如权利要求1至3任一项所述的鼻传送装置,其特征在于,所述传送装置还包括筒形部分,其连接到喷嘴上并且构造成接收将要传送至所述一个鼻孔中的物质。
5.如权利要求4所述的鼻传送装置,其特征在于,筒形部分包括一个腔室。
6.如权利要求1至3任一项所述的鼻传送装置,其特征在于,传送装置还包括供给单元,用于供应带有物质的气流至喷嘴中。
7.如权利要求6所述的鼻传送装置,其特征在于,供给单元构造成传送独立于呼气的气流。
8.如权利要求6所述的鼻传送装置,其特征在于,还包括控制单元,用于控制供给单元,从而控制传送的气流的流速。
9.如权利要求1所述的鼻传送装置,其特征在于,口呼气单元包括构造成在受治疗者呼气时移动通过套口的可动元件,而且传送单元还包括连接到喷嘴上并构造成接收传送至所述一个鼻孔的物质的筒形部分,以及可操作地连接到可动元件上的推进器,从而在使用中随可动元件运动并且产生通过筒形部分的气流,用于带走所述物质。
10.如权利要求9所述的鼻传送装置,其特征在于,筒形部分包括一个腔室。
11.如权利要求9所述的鼻传送装置,其特征在于,可动元件构造成作为气流阻挡件,并且对呼出的气流形成流动阻力。
12.如权利要求11所述的鼻传送装置,其特征在于,可动元件构造成保持在呼气时其上行区的至少大约10厘米水柱的正压。
13.如权利要求9至12任一项所述的鼻传送装置,其特征在于,可动元件是可转动的元件。
14.如权利要求9至12任一项所述的鼻传送装置,其特征在于,还包括分散单元,用于将一次剂量的物质分散进筒形部分中。
15.如权利要求1所述的鼻传送装置,其特征在于,传送装置包括套口和将套口连接至喷嘴的筒形部分,该筒形部分构造成接收将要传送的物质,从而通过套口的呼气传送药物通过喷嘴。
16.如权利要求15所述的鼻传送装置,其特征在于,筒形部分包括一个腔室。
17.如权利要求1至3任一项所述的鼻传送装置,其特征在于,传送单元还包括启动机构,用于在响应受治疗者呼气时启动传送单元。
18.如权利要求1至3任一项所述的鼻传送装置,其特征在于,传送单元构造成将带走物质的气流传送至所述一个鼻孔。
19.如权利要求18所述的鼻传送装置,其特征在于,传送单元构造成在驱动压力下传送气流,该驱动压力能使气流围绕受治疗者鼻中隔后区流动并从另一个鼻孔出来。
20.如权利要求18所述的鼻传送装置,其特征在于,还包括出气单元,其包括用于在受治疗者另一个鼻孔中配合的喷嘴和气流阻挡件,该气流阻挡件对于排出所述另一个鼻孔的气流提供阻力,从而在使用中保持其上行区的动力学正压。
21.如权利要求20所述的鼻传送装置,其特征在于,出气单元的气流阻挡件是可调节的,以允许流动阻力的调节。
22.如权利要求20所述的鼻传送装置,其特征在于,出气单元还包括指示器,用于在其上行区获得至少预定流速或压力之一时提供至少一个可视或可听信号。
23.如权利要求1至3任一项所述的鼻传送装置,其特征在于,传送单元还包括指示器,用于在受治疗者通过套口呼气时提供至少一个可视或可听信号。
24.如权利要求23所述的鼻传送装置,其特征在于,指示器包括显示元件,其在受治疗者通过套口呼气时移动进入视野。
25.如权利要求1至3任一项所述的鼻传送装置,其特征在于,物质是药物、用于清洁鼻道的清洁剂或者用于冲洗鼻道的冲洗剂中的一种或几种。
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GBGB9911686.5A GB9911686D0 (en) | 1999-05-19 | 1999-05-19 | Device |
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CNA2005100825927A Division CN1736502A (zh) | 1999-03-03 | 2000-03-03 | 鼻传送装置 |
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CN1217712C true CN1217712C (zh) | 2005-09-07 |
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CN008045585A Expired - Fee Related CN1217712C (zh) | 1999-03-03 | 2000-03-03 | 鼻传送装置 |
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EP (6) | EP1161274B1 (zh) |
JP (2) | JP4543553B2 (zh) |
KR (1) | KR100692422B1 (zh) |
CN (2) | CN1736502A (zh) |
AT (3) | ATE487506T1 (zh) |
AU (1) | AU766410B2 (zh) |
BR (1) | BR0008650B1 (zh) |
CA (1) | CA2364009C (zh) |
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SI (2) | SI1180378T1 (zh) |
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2000
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- 2000-03-03 DK DK00906570T patent/DK1161274T3/da active
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- 2000-03-03 DK DK04030887T patent/DK1555038T3/da active
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- 2000-03-03 KR KR1020017011177A patent/KR100692422B1/ko not_active IP Right Cessation
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2001
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2002
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- 2002-02-04 HK HK02106029.0A patent/HK1044492A1/zh unknown
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2004
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2006
- 2006-06-02 US US11/445,993 patent/US9119932B2/en active Active
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