CN1109102C - 用超声气流输注粒子的无针注射器 - Google Patents
用超声气流输注粒子的无针注射器 Download PDFInfo
- Publication number
- CN1109102C CN1109102C CN94191721A CN94191721A CN1109102C CN 1109102 C CN1109102 C CN 1109102C CN 94191721 A CN94191721 A CN 94191721A CN 94191721 A CN94191721 A CN 94191721A CN 1109102 C CN1109102 C CN 1109102C
- Authority
- CN
- China
- Prior art keywords
- described syringe
- nozzle
- particle
- air
- arbitrary
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/30—Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
- A61M5/3015—Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules for injecting a dose of particles in form of powdered drug, e.g. mounted on a rupturable membrane and accelerated by a gaseous shock wave or supersonic gas flow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/04—Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/89—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microinjection
- C12N15/895—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microinjection using biolistic methods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/42—Reducing noise
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
- A61M5/2053—Media being expelled from injector by pressurised fluid or vacuum
Abstract
一种无针注射器,包括一膜片(28),它在气压作用下破裂而生成喷射含有药剂的粒子的超声气流。
Description
先前的工作表明了使用密集载体粒子进行植物细胞的基因转移的可行性。在该生物学方法中,比方说用钨或金制成的密集弹射微粒涂上基因物质后射入靶子细胞中。如在WO-A-92/04439中所公开的,使用一种装置来发射弹射微粒,该装置包括一细长管状装置、一连接到该细长管状装置一端的可加压气室、在该装置两端之间用来存放或引入待发射粒子的装置以及一膜片,该膜片封住该管状装置中的气道,直到在气室气流的一定压力作用下发生破裂,从而粒子被管状装置的气流射出。如在该较早说明书中所公开的,粒子最初可因比方说静电而固定在一可破裂薄膜上或其上游,该薄膜在气体开始流动时破裂,它可与上述发生破裂而发动气流的可破裂膜片相同。或者,据说粒子也可通过一空心针注入气流中。
人们现在惊奇地发现,可改进现有技术而提供一种使用无针注射器的非侵害给药装置,该无针注射器把一定剂量的含药微粒射入未受损伤的皮肤中。
按照本发明的一个宽广方面,一无针注射器包括一细长管状喷嘴,一位于该喷嘴上游端旁、起初封住该喷嘴中的气道的可破裂膜片,位于该膜片旁的治疗剂粒子、特别是粉末状治疗剂以及一发动装置,该装置使一气压作用在该膜片的上游面,该气压足以破裂该膜片并在喷嘴中产生一传送这些粒子的超声气流。
该注射器可用于正规给药,例如治疗糖尿病的胰岛素,也可用于群众性防疫项目或缓慢释放药物的给药,例如止痛剂和避孕药。该注射器还可用于把基因物质注入皮肤活细胞中,以便为稳定治疗血友病或皮肤黑色素瘤之类的疾病长期提供基因疗法。该注射器还可用来把基因物质注入皮肤、肌肉、血、淋巴并在稍作外科手术的情况下注入到器管表面。
使用新型注射器的给药装置减少了传染病和自动免疫疾病的传染机会,而这些疾病现在都因重复使用针头等原因而传染。液体注射给药方法造成皮肤损伤和出血并且针头尚无法改进成能防止通过血液传染疾病。因此,本发明的主要优点是不使用针头、不造成痛苦;没有传染的危险;以自然的固态给药;比由注射器和针头注射药液更迅速和安全,并且无需处置针头。
初步的实验确证了一理论模型和该种新技术的功效,特别是皮注药粉的功效。该理论模型假定皮肤的行为与作为阻挡介质的水十分相象。因此,雷诺数为低值时该组力遵从斯托克斯定律(StokesLav),但雷诺数较高时阻力系数不变。B S Massey所著《流体力学》一书(Van Noserand出版社)中给出了水之类的均匀介质的光滑球面上的这种阻力行为的证据。计算表明,使用其大小不会损伤皮肤细胞的粉末状药物粒子,使用在可破裂膜片破裂时较容易获得的比方说1-8个马赫数、最好是1-3个马赫数的气流速度,药粉可渗透到皮肤之下比方说100-500μm。该渗透取决于粒子大小即当假定粒子大致为球状时的粒子标称直径、粒子密度、冲击皮肤时的初速度以及皮肤的密度和流动粘度。渗透深度取决于为获得最佳治疗而有待射入药物粒子的组织,例如表皮或肌肉,从而相应选择上述决定渗透的各参数。
本发明的一个特征是可严格控制该渗透深度,从而把特定药物送到所需部位。因此,此方说,对于在皮肤内起作用的药剂可把该渗透选择在小于1mm,对于皮下起作用的药剂可选择成1-2mm,而对于肌肉内起作用的药剂可选择成10mm或更大。并相应选择药剂本身。可使用的药剂的例子有免疫病毒或蛋白质、布洛芬之类的止痛剂、人体生长激素之类的激素以及胰岛素和降钙素之类的药物。该药剂可不用任何载体、稀释剂或其它密度增大剂。在某些情况下,例如为了提供含有高效药物的一定大小的粒子时,可使用某种载体,但其数量通常比在普通药物组成中小得多,例如占粒子的体积百分比小于75%或常常小于50%。例如,胰岛素和降钙素通常在皮下给药。HGH(人体生长激素)在皮下给药,或者少数情况下在肌肉内给药。甲型肝炎、脑膜炎和卡介菌免疫物可在肌肉内、皮下和皮肤内给药。
因此在第一例中,标称直径为10μm的胰岛素粒子以750m/sec的初速注入皮肤中。若假定胰岛素粒子的密度与皮肤相近、即约为1,并假定皮肤的流动粘度与水相近而为10-6m2/sec,渗入深度在粒子停在皮肤中之前约为200μm。若要获得更大渗透深度,可把粒子大小提高到20μm,初速提高到1500m/sec,此时渗透深度提高到约480μm。
在本新技术的第二应用例中,不是皮注,而是细胞的基因转移,例如把涂有DNA的钨载体粒子注入玉米细胞中,若要把这些粒子注入到组织中同样深度,则需减少粒子大小以便提高其密度。因此若这类涂有DNA的粒子的标称直径为1μm,密度约为20,以500m/sec的速度注入玉米细胞,则渗透深度约为200μm。
一般来说,这种新注射技术可使用的粒子大小为0.1-250μm,对于皮注药粉,最好为1-50μm,10-20μm则更佳。粒子的密度通常为0.1-25g/cm3,但对于皮注药粉,最好为0.5-2.0g/cm3,更好基本为1.0g/cm3。注入速度可为200-2500(甚至高达3000或以上)m/sec,但对于皮注药粉,最好为500-1500m/sec,而在750-1000m/sec中更好。
粉状药剂通常经碾磨并筛选到精确直径。或者,粒子也可以是比方说直径达100μm的微小球壳,其中灌装固体或液体药物。如果胶质壳体的渗透率可控,这就又可成为注入后缓慢释放药物的一种装置。为了使粒子具有顺利渗入所需的大小和质量,特别是如果药剂为烈性药或低密度,则必须使用大体为惰性的载体。该载体可与药剂混合,也可使用胶质壳体。所需剂量决定于一次喷射的药剂数量和浓度以及粒子数。
另一种设定新技术的可接受工作参数的方法是选择粒子大小、质量和初速以便获得一动量密度,即粒子动量除以粒子前端面积的值为2-10,最好为4-7kg/sec/m。为了使给药可控,并随组织的不同而不同,需要控制动量密度。在上述以750m/sec的速度喷射粒子大小为10μm的胰岛素药粉的第一例中,该动量密度为5kg/sec/m。在把涂有DNA的钨载体粒子注入玉米细胞中的第二例中,粒子的标称直径为1μm,速度为500m/sec,该动量密度为6.7kg/sec/m。
本发明还包括一治疗用无针注射器,它包括一喷嘴、药粉粒子以及发动装置,该发动装置开始时就以至少200、最好为200-2500m/sec的速度从该喷嘴喷出粒子,其中粒子大小主要为0.1-250μm,密度为0.1-25g/cm3,并且该药剂包括治疗用药物,并且,最好没有或只有少量隋性载体或稀释剂(即其体积百分比<50%)。
本发明还包括一种治疗方法,包括皮注药粉粒子,包括以至少200、最好为200-2500m/sec的速度把粒子皮注到一定部位,其中,粒子的大小大多为0.1-250μm,密度为0.1-25g/cm3,并且,药剂包括治疗用药物,并且,最好没有或只有少量隋性载体或稀释剂(即其体积百分比<50%)。
说到该注射器的构造,发动装置可包括一在膜片上游、通常在注射器把手中的一气室以及控制地提高该气室中气压的装置,此时在气室中提高气压的该装置可包括通过比方说一快速联接器和一排气阀与该气室连接的一压缩气体源,或者,该注射器也可以是自备的便携式,本身装有可更换的压缩气体储室。
一实际装置的典型工作值在一体积为1-5ml的高压室中的薄膜破裂压力为20-75大气压,从而产生速度为1-8马赫数、最好为1-3马赫数的超声震波。
离开喷嘴的气体/粒子速度并因而渗透深度决定于膜片破裂气压,但是令人惊奇的是,对于这种瞬变现象,实验表明该速度还在很大程度上决定于喷嘴的几何结构。这一点是很有用的,因为它使我们可通过改变喷嘴而不是改变膜片厚度来控制渗透深度。该喷嘴最好包括一收敛形上游部,它通过一喉部后通到一圆筒形、最好为发散形的下游部。该上游部供密封药剂件放入在一宽部中,而在喉部处产生超声震波。下游部的发散形状对气体膨胀到伪稳态速度即超声速度有极大影响。这一伪稳态速度的提高造成粒子渗透深度的增大,这对于被看作主要为瞬态的一种现象来说是令人惊奇的。该发散部在膜片破裂时似乎还把该瞬态流型转变成从喷嘴排出的平稳气流,从而使粒子均匀地传入其靶子。此外,喷嘴的发散形状使粒子均匀地扩散到靶子上。
在一组在膜片上游使用氦气并且只改变破裂气压的实验中,测量粒子渗入一均匀靶子的深度。42、61和100个大气压的破裂气压分别产生38、50和70单位的渗透深度。与此相对照,在只改变喷嘴发散部的内部结构进行同样实验也产生不同的渗透深度。从而选择成能产生1、2和3马赫数的长度和出口直径相同但内部结构不同的三个喷嘴分别产生15、21和34单位的靶子渗透深度。
用来传送粒子的气体类型似乎无关紧要,合适的有氦、氮和二氧化碳之类的较廉价气体。但是,作用在膜片上游一面上破裂该膜片的气体应该无菌,因为它用作通过喷嘴把粒子携带到病人皮肤或其它靶子上的气流。为此,氦是有用的,因为它可呈隋性、无菌形态。
人们现在认识到,用氦气破裂膜片还有一个优点。据认为,大多数粒子移动到起初由膜片隔开的上游气体与下游气体之间的接触面上,该接触面紧靠震波。情况似乎是,作用在膜片上游一面上的气体越轻,对于膜片破裂时膜片上的一定气压差和一定的喷嘴形状来说,喷嘴中的震波(以及接触面)速度就越大。从而,如果使用较轻气体,在较低气压差下即可获得所需震波速度,只要该气压差足以破裂膜片。因此一般要说,作用在膜片上游,一面上破裂该膜片的气体使用此空气轻的气体。
这一认识使人们进一步认识到,喷嘴中的震波的速度越大,喷嘴中的气体越轻。因此有人提出,至少部分使用真空,但实际上难于形成并保持真空。因此为了进一步减小获得所需震波(和接触面)速度的所需膜片破裂气压,喷嘴在膜片下游最好装上比空气轻、大致为大气压的气体,例如氦,该较轻气体在喷嘴下游端部用容易卸下的密封件、比方说可卸下的塞头或盖帽、或可揭去的金属片封住。使用时在起动注射器之前迅速取走该密封件,从而使该较轻气体在该注射器注射前没有时间扩散出喷嘴。
喷嘴下游端部的密封还有一个优点是,它可保持无菌,从而在比方说打开消毒包后、在该注射器喷射之前防止外物进入喷嘴,因为这类外物必然会被携带药物粒子的气流带到病人皮肤或其它靶子上。
粒子源应包含精确剂量的药物并且能用作消毒组件。事实上要求绝对无菌,因而据认为至少是管状喷嘴组件和粒子源的剩余物和破裂的膜片、可能还有可加压的气室将为一次性的,使用后用从密封消毒包取出的一新组件更换。极有可能整个装置、包括可加压气室、喷嘴、膜片和粒子,都是一次性的,从而整个注射器在使用后都被扔掉。这种一次性组件的制造自然尽可能便宜,特别可用塑料制造。也可把该注射器做成可,很方便地拆成两个部分:一至少包括无菌喷嘴、膜片和粒子的一次性下游部分和包括至少一部分发动装置的上游部分。但是在这种特别构造中,高压气流源及其与可加压气室连接的转接器不是一次性的,而是较贵重的金属部件。由于这些部件的外端和内表面与可加压室、从而与该喷药时的管状喷嘴的内部连通,因此存在被非一次性部件上细菌和其它污染物污染的危险。
因此最好气室的上游端部用一消毒隔板盖住,例如半渗透膜片,它容许气体通过,但不容许细菌通过。或者,气室可以是圆筒形,该消毒隔板为一活塞,加上在圆筒形气室中推动该活塞而压缩其中气体的装置。推动该活塞的装置可以是装在该活塞上游端的一压缩气体源。该注射器就成为自足的便携式,本身装有压缩气体储室以及一可用于打开而把气压加到活塞上的阀。或者,推动活塞的装置包括一平时处于压缩状态的弹簧,用于释放时推动该活塞。
由于有活塞,因此可确保,不管多慢地在圆筒形气室中移动活塞,起初在一定气压下的一定体积的气体的气压会提高,直到该气室中的气压足以破裂膜片而喷射出粒子。因此流过该管状装置的气体量是精确预定的,从而产生很小令人讨厌的噪声。若在推进活塞前把圆筒形气室中的氦气或其它气体预加压到比方说2巴的超大气压力,则把该气压提高到足以破裂膜片的比方说20-40巴所需的该气缸的工作容积可最小。此外,为了避免膜片紧在破裂之前鼓起而离开活塞而在活塞前端与膜片之间形成死空间,活塞的前端最好做成中凸形,以便更贴近膜片中央。
当临床使用该注射器喷药时,管状喷嘴、膜片、粒子、圆筒形气室、发动装置和活塞组件可放在一密封消毒包中待用,并在使用后扔掉。在包括一次性和非一次性部件的另一种结构中,由于活塞在整个喷药过程中可用作把活塞上游的非一次性部件与活塞下游的一次性部件隔开的隔板,因此可避免来自活塞后方的活塞推进装置的污染,不管该推进装置是一弹簧、一手动柱塞还是一高压流体源。
一次性组件自然用尽可能便宜材料制造,特别是塑料。由于喷药时圆柱形气室的气压升得很高,使气室壁向外撑开,从而气体有可能经活塞回漏,因此圆柱形气室的壁可用刚性工程塑料制成。或者也可用更便宜的办法,即使用时圆柱形气室以紧配合套在一刚性外壳中。
新型注射器的另一个应用是在实验室中把基因物质喷入活细胞中进行基因转移。此时,由于实验室本身基本无菌,因此可不必在无菌状态下预先组装一次性部件,而是在实验室中用独立(可能是一次性的)管状喷嘴和圆柱形气室件和一独立活塞件组装注射器,管状喷嘴和圆柱形气室件可拆开以便更换破裂的膜片,活塞件在把一定剂量的基因物质放到膜片上后插入圆柱形气室。
当粒子用高密度金属制成和/或进行植物细胞的基因转移时,此时有多少粒子能到达靶子是无关紧要的,因此可使用WO-A-92/04439公开的在膜片破裂前用来定位粒子的各种装置,但是,现有装置不适用于药粉,因为含药粒子很轻,喷射前很难不流动,给药量必须一定,并在喷药前得无菌。为此,药粉粒子最好装在横置在喷嘴内部的两片可破裂薄膜之间。
两薄膜之一、或者实际上两薄膜,可构成可破裂主膜片,膜片破裂引起气流。或者,该药粉件也可在喷嘴中任何方便位置上放置在可破裂主膜片的上游或下游。
该膜片和薄膜或多片薄膜可以是在一次性注射器或注射器的一次性部件中的永久性固定件,它们也可沿其边缘夹紧在喷嘴的两可连接部分之间,例如用螺纹连接在一起的两部分之间。
最好两薄膜的边缘沿其边缘直接密封在一起而形成一内装粒子的普通小袋或胶囊,或者间接密封,例如密封在一插入环的对置轴向面上。不管哪种情况,该密封件的边缘应可夹紧在喷嘴的可分开部分之间。
该小袋、胶囊或其它密封件可包括三片以上薄膜而形成多个内装一起喷射的不同药粉的相隔离小室。这可用来喷射各种药物的混合物,这些药物可能在干燥状态下发生不应有的反应。该密封件可用作无菌组件,内装精确剂量的药物。由于该密封件随着膜片的破裂而破裂,因此需要时可确保获得正确剂量的药物。喷射干燥药粉的本新技术的一个特别优点是,它能用来提供稳定的药物混合物;而若与液体相混合就会不稳定。本发明包括用于本发明注射器中的这样一种药粉混合物。
该密封件内装一定剂量的药物,重要的是,要把这一剂量大体全部地送到病人皮肤中。因此重要的是,薄膜破裂后基本上没有粒子残留在薄膜边缘处之间。为此,最好至少一薄膜鼓起而离开另一薄膜,从而两薄膜分得足够开,使大部分粒子位于从膜片边缘沿径向靠里的位置。
本发明还包括一治疗用产品,包括新注射器的、或用于新注射器的一密封件,该密封件包括沿其边缘相互直接或间接密封的两薄膜,内装皮注药粉粒子。
可以设想,喷嘴越靠近病人皮肤,粒子渗透深度越大。尽管这一点在该间距从约几十毫米的一距离逐渐减小时是正确的,但实验表明,存在一个最佳渗透的最佳间距,若喷嘴进一步靠近皮肤,渗透性反到大大下降,这也许是由于反射震波干涉接触面所致。
因此最好在喷嘴的下游出口端装一间隔件,从而使喷嘴离病人皮肤一段35mm、最好为5-15mm的有利间距。对于形成喷嘴与病人皮肤之间的这一间距的另一个要求是喷药离开喷嘴后能沿径向向外扩散而使粒子冲撞在比喷嘴横截面大得多的病人皮肤面积上。例如,若喷嘴下游端部开口的直径约为2.5mm,喷药的发散应能使它大致均匀地冲撞在直径约为20-30mm的病人皮肤面积上。因此最好是,该间隔件为一足够大的管形外罩,其形状做成这样,使用时它并不阻止由气流携带的含药粒子从喷嘴出口喷出后在与外罩下游端齐平的一位置上扩散成至少为喷嘴出口横截面5倍、最好至少为10倍的横截面积,该位置即为该外罩使用时抵住病人皮肤的位置。
该间隔件可与一消音器或棉毛之类的消音介质相联。多孔间隔件足以获得消毒效果,最好是,不在用作间隔件的管形外罩上打孔,而是把一消音器放置在套在喷嘴外的一圆筒中的环状空间中,以便接受通过间隔外罩从病人皮肤反射回来的震波。该消音器可以是迷宫式结构并且比方说在从喷嘴表面沿径向向外伸出的叉指式环形凸缘与从圆筒沿径向向里伸出的叉指或环形凸缘之间形成一曲曲折折的通道,该通道通过该圆筒口的至少一个出口与大气相通。这可十分有效地降低膜片破裂时以及震波离开喷嘴使粒子与病人皮肤相撞时发出的可怕噪声。
下例表示本发明无针注射器的功效。8个健康白化公鼠(Wistar,平均质量:250g)注射0.25ml Sagatal(戊巴比通钠sodium penthathol barbitone,60mg/ml)进行麻醉。用市场可售得的脱毛油(Immac)除去白鼠腹膜部的皮毛。然后对白鼠1-4用附图图1所示无针注射器注射0.1mg牛胰岛素(粉状,Sigma)。白鼠5-6在同样条件下注射1mg牛胰岛素。胰岛素粒子平均大小约为10μm,喷射速度为750m/sec。作为对照,白鼠7和8用现有注射器通过针头注射溶解在0.9%氯化钠溶液中的0.1mg胰岛素。
在注射前(用作对照)以及然后在注射后四小时采取每一个实验鼠的血样。每次从白鼠尾巴上取出3滴血(约50μl)后与2μl肝素混合以防止发生凝结。然后把此混合物与100μl的6%高氯酸混合以便中止葡萄糖代射。然后离心该混合物并测定上清液的血葡萄糖。
下表示出白鼠1-6的血葡萄糖浓度(BLG):
白鼠 | BLG(mM) | |
0小时 | 4小时 | |
1 | 5.30 | 2.22 |
2 | 5.40 | 1.29 |
3 | 7.22 | 1.51 |
4 | 5.64 | 2.87 |
5 | 5.07 | 0.91 |
6 | 5.36 | 2.63 |
白鼠7和8分别在1小时和2小时后的BGL测定值为2.2-3.3mM和2.0-2.4mM。从这些结果中显然可见,用无针注射可注入足够数量的胰岛素而产生很好治疗效果。该治疗效果足可与使用现有针头/注射器获得的效果相比拟。四小时的结果与其它结果的比较表明,工作气压的降低(以65巴到40巴)以及胰岛素“装药”的减少(从1.0mg减少到0.1mg)对BGL并无重大差别。这一点由于如下三个原因是极端重要的:
i)工作气压的降低降低了对大规模生产的医疗装置最终设计的结构要求;
ii)工作气压的降低确保消除了可能发生在靶子皮肤上的任何副作用;以及
iii)药物装药的减少表明本给药方法非常有效,确保使用本给药技术能充分获得生物有效性。
附图图示出本发明注射器的一些例子,附图中:
图1为第一例的轴向剖面图;
图2为第一例立视图;
图3为图1的分解图;
图4、5和6分别为本发明第2、第3和第4例的轴向剖面图;
图7为沿图6中VII-VII线剖取的剖面图;
图8为所示注射器中所使用的胶囊的轴向剖面图。
图1-3所示第一注射器约长18cm,可握在手掌中而以大姆指抵住上端。它包括一其中有一储气室11的上部圆筒部10。该圆筒部10的上端用一端塞12盖住,该端塞有一下悬裙部13。该圆筒部10下端由一与之连成一体的端壁14封住,该端壁14有一具有外螺纹的下悬裙部15。一柱塞16包括圆柱形上扩部和下扩部17和18,它们分别在裙部13和15中滑动。该滑动件的向上移动因扩部17的顶端抵靠盖帽12的一肩19而受到限制。该柱塞在下压固定在该柱塞16顶端的一按钮21时可从此位置向下移动一与图1所示间隙20相等的行程。在整个此行程中,扩部18靠一O形环22而保持与裙部13的密封。在该柱塞的举起位置上,扩部18靠一O形环23与裙部15密封而密封储气室11,但当下压柱塞时,该密封件移出裙部下端而以扩部18与裙部15之间的间隙形成储气室11的出气口。
一其中有一气压室25的下部圆筒部24用螺纹连接在上部圆筒部10的底部。一喷嘴26用螺纹连接在圆筒部件的下端中。一内装待喷射粒子的胶囊28固定并密封在喷嘴26的顶端与一与圆筒部24制成一体的环形突缘27之间。该胶囊依靠分别置于喷嘴和胶囊的凹槽内的O形环29和30与喷嘴26和突缘27密封。
如图8所示,该胶囊包括一环状环31,它有一截头圆锥形内周而圈成一室32,该室装有待喷射的粒子。该室的顶部用一较弱的Mylar薄膜33封住,底部用一较坚固的Mylar薄膜34封住。这些薄膜可用喷嘴26与突缘27之间的压缩力而与环31的顶壁和底壁密封,但最好用加热等方法与该环的表面粘接。从而该胶囊形成一自足的密封件。薄膜34可如虚线所示向下鼓起,以便确保使用中两薄膜破裂时所有粒子从该室中喷出。该环可在中间用第三较弱薄隔成两部分而形成两个独立小室。
穿过喷嘴26的气道包括一上部收敛(沿气流的向下方向)部35,它通过一喉部36而通向一发散部37。该收敛部为环31内部截头圆锥形的继续。读喷嘴外套一作为发射间隔罩38的一管状部以及被一直径上的纵向平面分为二半的圆柱形消音部39。这两个半消音部装到喷嘴的一圆柱形表面上,在这里它们由一环形突缘和凹槽41之间的啮合而获得定位。然后把这两个半消音部粘合在一起。圆筒部39内表面上有若干与之连成一体的在轴向上相间距、在径向上向里突起的突缘40。喷嘴的外表面上相应地有一列在径向上向外伸出的突缘41,每一突缘41在轴向上位于与一对相邻突缘40等距的位置上。突缘41的外径大于突缘40的内径。圆筒部39在靠近其上端处有一圈废气出口42。
圆筒部10最好可重复使用,并用金属或塑料制成。用螺纹连接到圆筒部10底部的各部件最好主要由塑料制成并为一次性的。在另一实施例中,整个注射器用塑料制成,装在消毒包中且为一次性。
使用时,用螺纹把一供气导管连接到裙部15上,并下压柱塞16使气流沿着扩部18向上充入储气室11,从而在气压下把氦之类气体充入圆筒部10中的储气室11。当放开按钮21时,柱塞16因供气气压作用在扩部18的下表面上而退回从而密封储气室11。
注射器的其余部分通常装在一密封消毒包中,其中胶囊28已到位,喷嘴26的气道中充有大体为大气压的氦之类的轻气体,并用一薄片43封住,该薄片43粘接在喷嘴底面上,薄片上有一拉片44,用此拉片即可揭去该薄片。这一部分用螺纹连接到圆筒部10上。
在进行注射时,把间隔罩38的较宽端紧压在病人皮肤上,首先拉动拉片44揭去薄片43,然后按下按钮21。从储气室11释放入气室25中的气体最终在气室中形成一足以破裂薄膜片33和34的气压并使该气流流过喷嘴26,从而气流携带粒子喷入病人皮肤中。从病人皮肤反射的震波向上穿过喷嘴26与周围圆筒部39间的迷宫式通道、穿过突缘40与41间的曲曲折折通道通道后最终从开口42流出,从而成为一消音器而减小放气噪声。
储气室11充一次气足以作5-10次注射,虽然本样机经一次注射后就得重新对储气室充气。注射后,通常至少得把连接到圆筒部10底部口的各一次性部件扔掉。但是,可以设想,在某些情况下,在进行下一次注射前可把喷嘴从圆筒部24底端旋下后装上一新胶囊28。若储气室含有足以进行多次注射的气体,则柱塞16最好可向上弹顶,从而注射器一注射完就放开按钮21而重新封用储气室底端。
图4表示一修正例,其中,上圆筒部10的顶端开口,其下端固定在一联接器54中,该联接器54用螺纹连接到下圆筒部24的顶端。该联接器有一装有一O形环46的插座,供一金属泡48上的颈部47插入并密封在该插座中。该金属泡内装氦之类的高压气体并松地装入到圆筒部10中。联接器45底壁上有一直立突起49,突起49中有一通道50通向气室25。一对向下伸展在圆筒部对置两侧的壁51在其下端的52处用枢轴与圆筒部10连接;在其上端的53处用驱轴与一杆54连接,该杆54有一可抵靠金属泡48顶端的凸轮鼻55。金属泡颈部47内装一顶弹阀,当如图4所示顺时针转动杆54而把金属泡48进一步压入插座50时,空心突起49向上压入该颈部而打开该阀。
图4中只简示出气室25下方的各部件,但可包括比方说图1-3所示间隔器/消音器和金属片密封件这类的所有零部件。工作情况与第一例相同,即当要对气室54加压进行注射时,可转动杆54而把气体从金属泡48释放入气室25。在该例中,某些部件或所有部件可是一次性的。
在上述两例中,一在供气时可用来过滤细菌和外物的半渗透性膜片可用其边缘装到圆筒部件上,例如装在圆筒部24的用螺纹连接的两部分之间,该半渗透性膜片在圆筒部24内横置在胶囊28的上游。
图5表示第一例的一修正例,图中虽然未画出,但该例包括与第一例相同的间隔器、消音器和金属薄片。主要的差别在于,圆筒部24更长并装有活塞56,该活塞用O形环57与圆筒部24内壁密封。该活塞因抵靠一环状肩58而固定在圆筒部24中。
在这种情况下气室25可以比方说2-4巴、甚或高达10巴的超大气压预充氦之类的气体。
使用时,按下按钮21而把活塞56在圆筒部24中下压一小段距离,然后从储气室11释放的气流就进入圆筒部24的活塞56后方而在气室25中下压活塞,直到活塞与胶囊28之间的气压足以破裂胶囊的薄膜。在此例中,圆筒部24最好可与圆筒部10分离而可与活塞56一起扔掉。
图6和图7所示注射器的一次性部件与图5所示相同,只是活塞56的形状稍有不同,它有一提升阀59,通过它可把气室25顶充气到超大气压气压。在该例中,上圆筒部10内装一滑动柱塞,该柱塞有一环状前端61,它可套住提升阀56而与活阀56连接。柱塞60起初借助一带槽锁眼板63克服一对平行的压缩圈簧而保持在退回位置上,该板63可在圆筒部10的顶端中横向滑动并与一杆64顶端中的对应环形凹槽啮合,该杆64用螺纹连接在该柱塞顶端处一扩部65中而有效地构成该柱塞的延伸部。弹簧62顶住在扩部61与该圆筒部中一插塞66上的一肩之间。带槽板63可用手柄67横向移动。
起初柱塞60处于提升位置,活塞56位于气室25顶端,此时如前所述,注射器底端处的间隔器抵靠在病人皮肤上。压下手把67使杆64和柱塞60脱扣,从而向前推动活塞56直到气室25的气压足以破裂胶囊28的薄膜。
在上述各例中,喷嘴26中的气道的几何结构极为重要,下面是一标称速度为2马赫的喷嘴的典型结构。收敛部35长10mm,从6mm直径收敛到喉部36处的1.5mm直径。发散部37长50mm,从喉部36向下到喷嘴出口端长度每增加5mm的直径分别为1.74、1.95、2.03、2.10、2.16、2.19、2.20、2.21、2.22和2.23mm。间隔罩38的轴向长度为30mm,从上游直径12mm发散到直径30mm。
在圆筒部3 4的壁体上设一通向一比方说氦气气源的进气口就可把图5-7所示例子改装成用于实验室。通过用该进气口就可间断地把气室25泵到初始气压2-4巴。此时,下部部件无需是一次性的,也无需预先装配。因此圆筒部10可为刚性结构并且位置可固定,粒子材料可装在圆筒部10与喷嘴间一密封件28的薄膜33、34之间。但在实验室中,那里只须放置一张膜片,在把活塞56装入圆筒部10顶部并通过进气口在该气缸中升压之前通过圆筒部10顶端把粒子材料投配到该膜片上。然后使驱动气流推动活塞56。
Claims (66)
1.一种无针注射器,它包括一细长管状喷嘴,一在该喷嘴上游端处、起初封住该喷嘴中的气道的可破裂膜片,位于该膜片处的粒子以及把一气压作用在该膜片上游一面的发动装置,该气压足以破裂该膜片,从而在该喷嘴中产生传送这些粒子的超声气流,其中,这些粒子为位于两片横置在该喷嘴内的可破裂薄膜之间的粉状注射剂。
2.按权利要求1所述的注射器,其中,该发动装置包括一在该膜片上游的气室和在该气室中可控制地提高气压的装置。
3.按权利要求2所述的注射器,其中,在气室中提高气压的该装置包括一通过一放气阀与该气室连接的压缩气体源。
4.按权利要求3所述的注射器,它是自备的便携式,本身装有压缩气体储室。
5.按权利要求2-4中任一权利要求所述的注射器,其中,气室的上游端用一无菌挡板封住。
6.按权利要求5所述的注射器,其中,该无菌挡板为一容许气体通过但不容许细菌通过的半渗透性膜片。
7.按权利要求6所述的注射器,其中,该气室为圆筒形,该无菌挡板为一活塞,还有在该圆筒形气室中推进该活塞而压缩其中气体的装置。
8.按权利要求7所述的注射器,其中,推进活塞的该装置为一装在该活塞上游端的一压缩气体源。
9.按权利要求8所述的注射器,它是自备的便携式,自身装有压缩气体储室以及一能用手打开而使该活塞受该气压作用的阀。
10.按权利要求7所述的注射器,其中,推进该活塞的装置包括一处于压缩状态的弹簧,然后用手释放而推进该活塞。
11.按权利要求7-10中任一权利要求所述的注射器,其中,该气室中的气体在活塞推进前起初为超大气气压。
12.按权利要求7-10中任一权利要求所述的注射器,其中,活塞的前端凸起。
13.按权利要求1-4中任一权利要求所述的注射器,其中,该发动装置包括一内装高压气体的泡,该泡有一用一顶弹阀封住的出口,该顶弹阀与该注射器中的一突起配合,该结构是这样的,该泡能向该突起推进,从而该突起打开该阀而使气体流出该泡。
14.按权利要求1-4和6-10中任一权利要求所述的注射器,其中,作用在该膜片上游一面破裂该膜片的气体比空气轻。
15.按权利要求1-4和6-10中任一权利要求所述的注射器,其中,至少有三片薄膜,从而在各相邻两片薄膜之间形成内装不同类型粒子的独立空间。
16.按权利要求1-4和6-10中任一权利要求所述的注射器,其中,该可破裂膜片为若干可破裂薄膜。
17.按权利要求1-4和6-10中任一权利要求所述的注射器,其中,这些薄膜沿其边缘密封在一起而构成一内装粒子的普通小袋或胶囊。
18.按权利要求1-4和6-10中任一权利要求所述的注射器,其中,两薄膜中的至少一个鼓起而离开另一薄膜,从而该两薄膜分得足够开而使大部分粒子位于从薄膜边缘沿径向靠里位置上。
19.按权利要求1-4和6-10中任一权利要求所述的注射器,其中,喷嘴内在该膜片的下游装有比空气轻的超大气压的气体,该轻气体用喷嘴下游端部处一很容易卸下的密封件封住。
20.按权利要求19所述的注射器,其中,该密封件为一可卸下的塞子或帽子。
21.按权利要求19所述的注射器,其中,该密封件为一可揭去的金属薄片。
22.按权利要求19所述的注射器,其中,装在该喷嘴中的气体为氦气。
23.按权利要求1-4、6-10和20-22中任一权利要求所述的注射器,其中,该喷嘴在该膜片的下游为收敛/发散形或收敛/圆柱形。
24.按权利要求1-4、6-10和20-22中任一权利要求所述的注射器,其中,该喷嘴下游端部处有一间隔器,从而在该喷嘴与一靶子之间形成一可靠间距。
25.按权利要求24所述的注射器,该间距最高达35mm。
26.按权利要求25所述的注射器,其中,该间距为5-15mm。
27.按权利要求24所述的注射器,其中,该间隔器为一足够大的管状罩,其形状做成这样:使用时它并不阻止从喷嘴出口喷出的由气流携带的粒子在一与该罩下游端齐平的位置上扩散成一至少为该喷嘴出口的横截面积5倍的横截面积。
28.按权利要求24所述的注射器,其中,该管状罩间隔器上不开有小孔,而是一消音器位于一套在管状喷嘴外的圆筒内的一环形空间中,用来接收从该靶子通过间隔罩反射回来的震波。
29.按权利要求1-4、6-10、20-22和25-28中任一权利要求所述的注射器,它可方便地拆成两部分:一包括喷嘴、膜片和粒子的一次性下游部分和一包括一部分发动装置的上游部分。
30.按权利要求29所述的注射器,当从属于权利要求6-10中至少任一权利要求时,该一次性部分也包括该气室和无菌挡板。
31.一种内装一易于与一上游部分分离并包括一喷嘴、膜片和粒子的一次性下游部分的消毒包。
32.按权利要求1-4、6-10、20-22、25-28和30中任一权利要求所述的注射器,它在进行注射时,在喷嘴中以200-2500m/sec的速度传送粒子,这些粒子的大小主要为0.1-250μm,其密度为0.1-25g/cm3。
33.按权利要求32所述的注射器,其中,该速度为500-1500m/sec。
34.按权利要求33所述的注射器,其中,该速度为750-1000m/sec。
35.按权利要求32所述的注射器,其中,粒子大小为1-50μm。
36.按权利要求35所述的注射器,其中,粒子大小至少为10μm。
37.按权利要求36所述的注射器,其中,粒子大小为10-20μm。
38.按权利要求32所述的注射器,其中,粒子密度为0.5-2.0g/cm3。
39.按权利要求1-4、6-10、20-22、25-28、30和33-37中任一权利要求所述的注射器,其中,所述的注射剂为药剂。
40.一种治疗用产品,它包括按上述权利要求1-4、6-10、20-22、25-28、30和33-38中任一权利要求所述注射器的或用于该注射器的一密封件,该密封件包括两薄膜,该两薄膜沿其边缘直接或间接互相密封,并且该密封件内装皮注用粉状注射剂粒子。
41.按权利要求40所述的产品,它做成一可破裂的密封小袋或胶囊。
42.按权利要求41所述的产品,其中,该小袋包括至少三片薄膜,从而形成至少两个内装可一起注射的不同粉状注射剂的小室。
43.按权利要求40所述的产品,其中,该粉状制剂为各药物的稳定混合物,而这些药物与液体混合就会不稳定。
44.按权利要求40所述的产品,其中,该粉状制剂包括胰岛素。
45.按权利要求40所述的产品,其中,这些粒子的大小主要为0.1-250μm。
46.按权利要求45所述的产品,其中,粒子大小为1-50μm。
47.按权利要求46所述的产品,其中,粒子大小至少为10μm。
48.按权利要求47所述的产品,其中,粒子大小为10-20μm。
49.按权利要求41-48中任一权利要求所述的产品,其中,所述的注射剂为药剂。
50.一种无针注射器,它包括一管状喷嘴、处于上述喷嘴上游的粉状注射剂粒子以及处于上述粒子上游的发动装置,该发动装置开动时以200-2500m/sec的速度在喷嘴中传送这些粒子,其中,粒子大小主要为10-250μm,其密度为0.1-25g/cm3。
51.按权利要求50所述的注射器,其中,该注射剂没有或只有少量体积百分比的隋性载体或稀释剂。
52.按权利要求50或51所述的注射器,其中,该速度为500-1500m/sec。
53.按权利要求52所述的注射器,其中,该速度为750-1000m/sec。
54.按权利要求50、51和53中任一权利要求所述的注射器,其中,粒子大小为1-50μm。
55.按权利要求54所述的注射器,其中,粒子大小为至少10μm。
56.按权利要求54所述的注射器,其中,粒子大小为10-20μm。
57.按权利要求50、51、53、55和56中任一权利要求所述的注射器,其中,粒子密度为0.5-2.0g/cm3。
58.按权利要求50、51、53、55和56中任一权利要求所述的注射器,其中,该制剂为各药物的稳定混合物,而这些药物与液体混合就会不稳定,或者,该制剂包括胰岛素。
59.按权利要求51、53、55和56中任一权利要求所述的注射器,其中,所述注射剂为药剂。
60.一种无针注射器,它包括一喷嘴、处于上述喷嘴上游的粉状注射剂粒子以及处于上述粒子上游的发动装置,该发动装置开动时以2-10kg/sec/m的动量密度传送粒子。
61.按权利要求60所述的注射器,其中,该动量密度为4-7kg/sec/m。
62.按权利要求60或61所述的注射器,其中,所述注射剂为药剂。
63.一种无针注射器,它包括:一细长体,该细长体包括一上游圆筒部和一下游管状喷嘴部,该上游圆筒部使用时包括一高压气源,而该下游管状喷嘴中有一气道,该气道包括一较短上游收敛形部和一较长下游圆柱形或发散形部,该圆筒部和喷嘴部以端部相互可拆开地连接在一起,它们连接在一起时其间放置一内装注射剂粒子的药丸;突然释放气流从而在喷嘴气道中形成一传送粒子的超声气流的装置;套在并伸出在喷嘴部下游端部上的一外罩,从而使该喷嘴端部与病人的组织相间距,并在喷嘴部与该外罩之间的环形空间中设有一消音器,用来消耗使用时从病人组织反射的震波的能量。
64.按权利要求63所述的注射器,其中,突然释放气流的该装置包括一在该喷嘴上游端处的可破裂膜片,它在足够大的气压作用其上时会破裂。
65.按权利要求63或64所述的注射器,其中,该气源为一压缩气体泡,它有一个用一顶弹阀关上的出口,该顶弹阀与该圆筒部中的一突起配合,其结构是这样的,在该圆筒中向下推动该泡就能使该突起打开该阀而从该泡释放气流。
66.按权利要求63或64所述的注射器,其中,所述的注射剂为药剂。
Applications Claiming Priority (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB939307459A GB9307459D0 (en) | 1993-04-08 | 1993-04-08 | Particle delivery apparatus |
GB9307459.9 | 1993-04-08 | ||
GB9318407.5 | 1993-09-06 | ||
GB939318407A GB9318407D0 (en) | 1993-09-06 | 1993-09-06 | Particle delivery apparatus |
GB939321356A GB9321356D0 (en) | 1993-10-15 | 1993-10-15 | Particle delivery apparatus |
GB9321356.9 | 1993-10-15 | ||
GB939326069A GB9326069D0 (en) | 1993-12-21 | 1993-12-21 | Particle delivery apparatus |
GB9326069.3 | 1993-12-21 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1120852A CN1120852A (zh) | 1996-04-17 |
CN1109102C true CN1109102C (zh) | 2003-05-21 |
Family
ID=27451010
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN94191721A Expired - Lifetime CN1109102C (zh) | 1993-04-08 | 1994-04-08 | 用超声气流输注粒子的无针注射器 |
Country Status (32)
Country | Link |
---|---|
US (5) | US5630796A (zh) |
EP (4) | EP1637173B1 (zh) |
JP (4) | JP3260375B2 (zh) |
KR (1) | KR100332147B1 (zh) |
CN (1) | CN1109102C (zh) |
AT (2) | ATE329006T1 (zh) |
AU (1) | AU674742B2 (zh) |
BG (1) | BG61993B1 (zh) |
BR (1) | BR9406455A (zh) |
CA (1) | CA2159452C (zh) |
CZ (1) | CZ290476B6 (zh) |
DE (2) | DE69401651T2 (zh) |
DK (2) | DK0734737T3 (zh) |
ES (2) | ES2098131T3 (zh) |
FI (1) | FI120671B (zh) |
GR (1) | GR3022939T3 (zh) |
HK (1) | HK1000351A1 (zh) |
HU (2) | HU228144B1 (zh) |
LV (1) | LV11833B (zh) |
NO (1) | NO314570B1 (zh) |
NZ (1) | NZ263606A (zh) |
OA (1) | OA10234A (zh) |
PL (1) | PL174974B1 (zh) |
PT (1) | PT734737E (zh) |
RO (1) | RO118569B1 (zh) |
RU (1) | RU2129021C1 (zh) |
SI (2) | SI0693119T1 (zh) |
SK (1) | SK283855B6 (zh) |
TJ (1) | TJ248B (zh) |
TW (2) | TW404844B (zh) |
UA (1) | UA41360C2 (zh) |
WO (1) | WO1994024263A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101797411A (zh) * | 2010-03-18 | 2010-08-11 | 傅雅芬 | 一种气压式无针注射器动力头 |
Families Citing this family (303)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW404844B (en) | 1993-04-08 | 2000-09-11 | Oxford Biosciences Ltd | Needleless syringe |
ES2247248T3 (es) * | 1994-01-21 | 2006-03-01 | Powderject Vaccines, Inc. | Instrumento de administracion de genes movido por gas comprimido. |
US5899880A (en) * | 1994-04-08 | 1999-05-04 | Powderject Research Limited | Needleless syringe using supersonic gas flow for particle delivery |
ES2208687T3 (es) * | 1994-08-04 | 2004-06-16 | Elan Drug Delivery Limited | Sistema de administracion de sustancias solidas para la liberacion controlada de moleculas incorporadas en tales sustancias y procedimientos para la fabricacion de tales sistemas. |
US6586006B2 (en) | 1994-08-04 | 2003-07-01 | Elan Drug Delivery Limited | Solid delivery systems for controlled release of molecules incorporated therein and methods of making same |
US6290991B1 (en) | 1994-12-02 | 2001-09-18 | Quandrant Holdings Cambridge Limited | Solid dose delivery vehicle and methods of making same |
GB9416663D0 (en) * | 1994-08-17 | 1994-10-12 | Oxford Bioscience Limited | Particle delivery |
GB9426379D0 (en) * | 1994-12-23 | 1995-03-01 | Oxford Biosciences Ltd | Particle delivery |
GB9502879D0 (en) * | 1995-02-14 | 1995-04-05 | Oxford Biosciences Ltd | Particle delivery |
US5766901A (en) * | 1995-05-04 | 1998-06-16 | The Board Of Trustees Of The Leland Stanford Junior University | Apparatus and method for delivering a nucleotide into cell nuclei |
US6474369B2 (en) | 1995-05-26 | 2002-11-05 | Penjet Corporation | Apparatus and method for delivering a lyophilized active with a needle-less injector |
US7223739B1 (en) | 1995-06-07 | 2007-05-29 | Powderject Vaccines, Inc. | Adjuvanted genetic vaccines |
ATE240482T1 (de) * | 1995-08-02 | 2003-05-15 | Boc Group Plc | Gaszuführvorrichtung |
GB9515846D0 (en) * | 1995-08-02 | 1995-10-04 | Boc Group Plc | Gas capsule |
US6080130A (en) * | 1998-11-14 | 2000-06-27 | Castellano; Thomas P. | Gas power source for a needle-less injector |
US6013050A (en) * | 1995-10-20 | 2000-01-11 | Powderject Research Limited | Particle delivery |
GB9605690D0 (en) * | 1996-03-19 | 1996-05-22 | Oxford Biosciences Ltd | Particle delivery |
AU3397597A (en) * | 1996-06-14 | 1998-01-07 | Powderject Vaccines, Inc. | Sample delivery module for particle acceleration apparatus |
US6893664B1 (en) | 1996-06-17 | 2005-05-17 | Powderject Research Limited | Particle delivery techniques |
JP2000513967A (ja) | 1996-07-01 | 2000-10-24 | フアーマシア・アンド・アツプジヨン・アー・ベー | 分配装置およびその操作方法 |
CA2209406C (en) | 1996-07-24 | 2007-05-15 | David W. Birch | Gas capsule and gas delivery system |
US6468782B1 (en) | 1996-12-05 | 2002-10-22 | Quadrant Healthcare (Uk) Limited | Methods of preserving prokaryotic cells and compositions obtained thereby |
DE19701494A1 (de) | 1997-01-17 | 1998-07-23 | Boehringer Mannheim Gmbh | Transdermales Injektionssystem |
US5947928A (en) * | 1997-06-19 | 1999-09-07 | Mile Creek Capital, Llc | Drug delivery system |
EP0888791A1 (en) * | 1997-07-04 | 1999-01-07 | PowderJect Research Limited | Syringe and drug capsule therefor |
EP0888790A1 (en) * | 1997-07-04 | 1999-01-07 | PowderJect Research Limited | Drug particle delivery device |
US6074360A (en) * | 1997-07-21 | 2000-06-13 | Boehringer Mannheim Gmbh | Electromagnetic transdermal injection device and methods related thereto |
US6171276B1 (en) | 1997-08-06 | 2001-01-09 | Pharmacia & Upjohn Ab | Automated delivery device and method for its operation |
US20060165606A1 (en) | 1997-09-29 | 2006-07-27 | Nektar Therapeutics | Pulmonary delivery particles comprising water insoluble or crystalline active agents |
DE19820172A1 (de) * | 1997-09-30 | 2005-01-27 | Wolfgang Wagner | Einrichtung und einrichtungsbezogenes Verfahren zur Einbringung eines Diagnostikträgers oder einer Arznei unter die Haut eines Lebewesens |
PT1032429E (pt) * | 1997-11-20 | 2003-10-31 | Aventis Pasteur | Metodo para aplicacao de adn in vivo utilizando um aparelho sem agulha |
NZ504894A (en) * | 1997-12-02 | 2002-12-20 | Powderject Vaccines Inc | Crystalline vaccine and adjuvant compositions jointly and separately administered to animals using a transdermal or transmucosally delivery technique |
JP2003528024A (ja) * | 1997-12-16 | 2003-09-24 | バレンティス・インコーポレーテッド | 製剤化された核酸分子の無針注入 |
GB9802508D0 (en) * | 1998-02-05 | 1998-04-01 | Boc Group Plc | Needleless medical device |
GB9802506D0 (en) | 1998-02-05 | 1998-04-01 | Boc Group Plc | Needleless medical device |
US6686339B1 (en) | 1998-08-20 | 2004-02-03 | Aventis Pasteur Limited | Nucleic acid molecules encoding inclusion membrane protein C of Chlamydia |
US6693087B1 (en) | 1998-08-20 | 2004-02-17 | Aventis Pasteur Limited | Nucleic acid molecules encoding POMP91A protein of Chlamydia |
AU5366099A (en) | 1998-08-20 | 2000-03-14 | Connaught Laboratories Limited | Nucleic acid molecules encoding inclusion membrane protein of (chlamydia) |
GB9818627D0 (en) * | 1998-08-26 | 1998-10-21 | Glaxo Group Ltd | Improvements in dva vaccination |
GB9819272D0 (en) * | 1998-09-03 | 1998-10-28 | Andaris Ltd | Microparticles |
ATE237277T1 (de) | 1998-09-04 | 2003-05-15 | Powderject Res Ltd | Zweite medizinische indikation einer partikelverabreichungsmethode |
US6602678B2 (en) | 1998-09-04 | 2003-08-05 | Powderject Research Limited | Non- or minimally invasive monitoring methods |
WO2000014547A1 (en) * | 1998-09-04 | 2000-03-16 | Powderject Research Limited | Immunodiagnostics using particle delivery methods |
USD434848S (en) * | 1998-09-08 | 2000-12-05 | Powderject Research Limited | Disposable injector |
PT1117382E (pt) * | 1998-10-01 | 2005-08-31 | Powderject Res Ltd | Microparticulas revestidas por pulverizacao para utilizacao em seringas sem agulha |
EP1123396B1 (en) * | 1998-10-19 | 2006-03-08 | Powderject Vaccines, Inc. | Minimal promoters and uses thereof |
FR2785293B1 (fr) | 1998-10-30 | 2002-07-05 | Pasteur Merieux Serums Vacc | Acides nucleiques et polypeptides specifiques des souches pathogenes du genre neisseria |
US6881723B1 (en) | 1998-11-05 | 2005-04-19 | Powderject Vaccines, Inc. | Nucleic acid constructs |
US6264629B1 (en) | 1998-11-18 | 2001-07-24 | Bioject, Inc. | Single-use needle-less hypodermic jet injection apparatus and method |
GB9825763D0 (en) * | 1998-11-25 | 1999-01-20 | Boc Group Plc | Filling containers with gas |
CA2358584A1 (en) * | 1999-01-22 | 2000-07-27 | Powderject Research Limited | Method of enhancing needleless transdermal powdered drug delivery |
US20070196490A1 (en) * | 1999-01-22 | 2007-08-23 | Powderject Research Limited | Method of enhancing needleless transdermal powered drug delivery |
US6328714B1 (en) | 1999-01-29 | 2001-12-11 | Powderject Research Limited | Particle delivery device |
US6849060B1 (en) * | 1999-01-29 | 2005-02-01 | Powderject Research Limited | Particle delivery device |
EP1146861B1 (en) * | 1999-02-03 | 2005-06-29 | PowderJect Research Limited | Hydrogel particle formulations |
US7022320B1 (en) | 1999-02-09 | 2006-04-04 | Powderject Vaccines, Inc. | Mycobacterium tuberculosis immunization |
NZ513981A (en) * | 1999-03-08 | 2004-02-27 | Powderject Res Ltd | Delivery of microparticle formulations using needleless syringe device for sustained-release of bioactive compounds |
US20050214227A1 (en) * | 1999-03-08 | 2005-09-29 | Powderject Research Limited | Microparticle formulations for sustained-release of bioactive compounds |
GB9905933D0 (en) * | 1999-03-15 | 1999-05-05 | Powderject Res Ltd | Neeedleless syringe |
US7013617B2 (en) | 1999-04-01 | 2006-03-21 | The Boc Group, Plc | Method of filling and sealing |
ATE244558T1 (de) | 1999-04-16 | 2003-07-15 | Novo Nordisk As | Trockene formbare arzneistoffformulierung |
AU765843B2 (en) * | 1999-04-16 | 2003-10-02 | Powderject Research Limited | Needleless syringe |
US7060048B1 (en) * | 1999-04-16 | 2006-06-13 | Powerject Research Limited | Needleless syringe |
FR2796290B1 (fr) | 1999-07-16 | 2001-09-14 | Cross Site Technologies | Seringue sans aiguille fonctionnant avec un generateur d'onde de choc a travers une paroi |
GB9916800D0 (en) * | 1999-07-16 | 1999-09-22 | Powderject Res Ltd | Needleless syringe |
FR2796288B1 (fr) * | 1999-07-16 | 2001-08-10 | Cross Site Technologies | Seringue sans aiguille avec injecteur a elements emboites |
US6319224B1 (en) * | 1999-08-20 | 2001-11-20 | Bioject Medical Technologies Inc. | Intradermal injection system for injecting DNA-based injectables into humans |
US20050027239A1 (en) * | 1999-08-20 | 2005-02-03 | Stout Richard R. | Intradermal injection system for injecting DNA-based injectables into humans |
US6811783B1 (en) | 1999-09-07 | 2004-11-02 | Aventis Pasteur Limited | Immunogenic compositions for protection against chlamydial infection |
DE19946059A1 (de) * | 1999-09-25 | 2001-03-29 | Roche Diagnostics Gmbh | System zur transdermalen Gewinnung von Körperflüssigkeit |
GB9923306D0 (en) | 1999-10-01 | 1999-12-08 | Isis Innovation | Diagnostic and therapeutic epitope, and transgenic plant |
EP1220697B1 (en) | 1999-10-11 | 2004-12-29 | Felton International, Inc. | Universal anti-infectious protector for needleless injectors |
DE60038971D1 (de) | 1999-10-22 | 2008-07-03 | Aventis Pasteur | Verfahren zur erregung und/oder verstärkung der immunantwort gegen tumorantigene |
KR20010108053A (ko) * | 1999-10-29 | 2001-12-07 | 무라야마 마사노리 | 당뇨병성 허혈성 질환 유전자 치료 |
US7196066B1 (en) | 1999-11-03 | 2007-03-27 | Powderject Vaccines, Inc. | DNA-vaccines based on constructs derived from the genomes of human and animal pathogens |
US20040234539A1 (en) * | 1999-11-03 | 2004-11-25 | Powderject Research Limited | Nucleic acid vaccine compositions having a mammalian cd80/cd86 gene promoter driving antigen expression |
FR2800619B1 (fr) * | 1999-11-05 | 2002-02-08 | Cross Site Technologies | Seringue sans aiguille avec un moyen de poussee temporairement retenu |
US20040109874A1 (en) * | 1999-11-10 | 2004-06-10 | Powderject Vaccines, Inc. | Induction of mucosal immunity by vaccination via the skin route |
US7029457B2 (en) | 1999-11-23 | 2006-04-18 | Felton International, Inc. | Jet injector with hand piece |
US7887506B1 (en) | 1999-11-23 | 2011-02-15 | Pulse Needlefree Systems, Inc. | Safety mechanism to prevent accidental patient injection and methods of same |
US6770054B1 (en) | 1999-11-23 | 2004-08-03 | Felton International, Inc. | Injector assembly with driving means and locking means |
FR2802102B1 (fr) | 1999-12-08 | 2002-07-12 | Poudres & Explosifs Ste Nale | Seringue sans aiguille munie d'un tube d'ejection a section constante |
FR2802103B1 (fr) | 1999-12-08 | 2003-10-03 | Poudres & Explosifs Ste Nale | Seringue sans aiguille fonctionnant avec entrainement du principe actif par effet tube a choc |
FR2802820B1 (fr) * | 1999-12-27 | 2002-10-18 | Poudres & Explosifs Ste Nale | Seringue sans aiguille fonctionnant par effet tube a choc, avec maintien prealable du principe actif sur le cote |
FR2804329B1 (fr) | 2000-02-02 | 2002-12-13 | Poudres & Explosifs Ste Nale | Seringue sans aiguille munie d'un opercule contenant le principe actif |
US6689092B2 (en) | 2000-03-03 | 2004-02-10 | Boehringer International Gmbh | Needle-less injector of miniature type |
GB0006263D0 (en) * | 2000-03-15 | 2000-05-03 | Powderject Res Ltd | Apparatus and method for adjusting the characteristics of a needleless syringe |
US6716190B1 (en) * | 2000-04-19 | 2004-04-06 | Scimed Life Systems, Inc. | Device and methods for the delivery and injection of therapeutic and diagnostic agents to a target site within a body |
EP1792995A3 (en) | 2000-05-08 | 2007-06-13 | Sanofi Pasteur Limited | Chlamydia secretory locus orf and uses thereof |
ATE513913T1 (de) | 2000-05-10 | 2011-07-15 | Sanofi Pasteur Ltd | Durch mage minigene kodierte immunogene polypeptide und ihre verwendungen |
US7871598B1 (en) | 2000-05-10 | 2011-01-18 | Novartis Ag | Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use |
AU2001268762A1 (en) * | 2000-05-26 | 2001-12-03 | George Vizirgianakis | Treatment and therapy apparatus |
US20020120228A1 (en) * | 2000-06-08 | 2002-08-29 | Yuh-Fun Maa | Powder compositions |
US7597692B2 (en) * | 2000-06-08 | 2009-10-06 | Massachusetts Institute Of Technology | Microscission processes and procedures |
US20040213798A1 (en) * | 2000-06-08 | 2004-10-28 | Powderject Vaccines, Inc. | Spray-dried alum compositions |
US6706032B2 (en) * | 2000-06-08 | 2004-03-16 | Massachusetts Institute Of Technology | Localized molecular and ionic transport to and from tissues |
CN1438874A (zh) * | 2000-06-08 | 2003-08-27 | 宝德杰克特疫苗有限公司 | 粉末组合物 |
GB0018035D0 (en) | 2000-07-21 | 2000-09-13 | Powderject Res Ltd | Needleless syringe |
US20020051821A1 (en) * | 2000-09-08 | 2002-05-02 | Sung-Yun Kwon | Aliginate particle formulation |
US6824822B2 (en) * | 2001-08-31 | 2004-11-30 | Alkermes Controlled Therapeutics Inc. Ii | Residual solvent extraction method and microparticles produced thereby |
US6742721B2 (en) * | 2000-09-25 | 2004-06-01 | Evit Laboratories | Shock wave aerosolization method and apparatus |
US6981660B2 (en) * | 2000-09-25 | 2006-01-03 | Evit Labs | Shock wave aerosolization apparatus and method |
GB0025147D0 (en) | 2000-10-13 | 2000-11-29 | Torsana Diabetes Diagnostics A | Optical sensor for in situ measurement of analytes |
ES2332261T3 (es) | 2000-11-27 | 2010-02-01 | Powderject Vaccines, Inc. | Adyuvantes de acidos nucleicos. |
US7150409B2 (en) * | 2000-11-30 | 2006-12-19 | Biovalve Technologies, Inc. | Injection systems |
GB0100756D0 (en) * | 2001-01-11 | 2001-02-21 | Powderject Res Ltd | Needleless syringe |
US6722364B2 (en) * | 2001-01-12 | 2004-04-20 | Becton, Dickinson And Company | Medicament inhalation delivery devices and methods for using the same |
US6644309B2 (en) | 2001-01-12 | 2003-11-11 | Becton, Dickinson And Company | Medicament respiratory delivery device and method |
US6443152B1 (en) | 2001-01-12 | 2002-09-03 | Becton Dickinson And Company | Medicament respiratory delivery device |
ES2191528B1 (es) * | 2001-02-05 | 2004-06-16 | Danone, S.A. | Dispositivo para la dosificacion de substancias liquidas. |
GB0103348D0 (en) * | 2001-02-10 | 2001-03-28 | Medical Res Council | Delivery of biologically active agents |
WO2002074406A1 (en) | 2001-03-14 | 2002-09-26 | Penjet Corporation | System and method for removing dissolved gas from a solution |
CA2441530A1 (en) | 2001-03-19 | 2002-09-26 | Iomai Corporation | Transcutaneous immunostimulation |
US6613010B2 (en) | 2001-04-13 | 2003-09-02 | Penjet Corporation | Modular gas-pressured needle-less injector |
US20050192530A1 (en) * | 2001-04-13 | 2005-09-01 | Penjet Corporation | Method and apparatus for needle-less injection with a degassed fluid |
WO2002087663A2 (en) | 2001-04-27 | 2002-11-07 | Penjet Corporation | Method and apparatus for filling or refilling a needle-less injector |
DE10121255A1 (de) * | 2001-04-30 | 2002-11-07 | Switch Biotech Ag | Verwendung von alpha 1-Antichymotrypsin Polypeptiden oder diese kodierende Nukleinsäuren, oder einer ein ACT Polypeptid oder diese kodierende Nukleinsäure exprimierende Zelle, zur Behandlung und/oder Prävention von diabetes-assoziierten und/oder arteriellen schlecht heilenden Wunden und zur Identifizierung von pharmakologisch aktiven Substanzen |
US6648850B2 (en) * | 2001-06-08 | 2003-11-18 | Bioject, Inc. | Durable needle-less jet injector apparatus and method |
AU2002302814A1 (en) * | 2001-06-08 | 2002-12-23 | Powderject Vaccines, Inc. | Spray freeze-dried compositions |
GB0118266D0 (en) | 2001-07-26 | 2001-09-19 | Powderject Res Ltd | Silencing device and method for needleless syringe |
US8061006B2 (en) | 2001-07-26 | 2011-11-22 | Powderject Research Limited | Particle cassette, method and kit therefor |
US20030019558A1 (en) * | 2001-07-26 | 2003-01-30 | Smith Edward R. | Particle cassette, method and kit therefor |
NZ531173A (en) * | 2001-07-26 | 2005-06-24 | Powderject Res Ltd | Particle cassette, method and kit therefor |
DE10163327A1 (de) * | 2001-07-30 | 2003-02-27 | Disetronic Licensing Ag | Reservoirmodul mit Kolbenstange |
DE10163326A1 (de) * | 2001-07-30 | 2003-02-27 | Disetronic Licensing Ag | Verabreichungsgerät mit Dosiervorrichtung |
DE10163325B4 (de) * | 2001-07-30 | 2005-07-28 | Tecpharma Licensing Ag | Verriegelungssperre für eine Verbindung von Gehäuseabschnitten eines Verabreichungsgeräts |
DE20112501U1 (de) * | 2001-07-30 | 2002-12-19 | Disetronic Licensing Ag | Verriegelungssperre für eine Verbindung von Gehäuseteilen eines Injektions- oder Infusionsgeräts |
DE10163328B4 (de) * | 2001-07-30 | 2005-08-11 | Tecpharma Licensing Ag | Verabreichungsgerät mit Verdrehsicherung |
US20050191361A1 (en) * | 2001-08-03 | 2005-09-01 | Powederject Research Ltd. | Hydrogel particle formation |
US6824526B2 (en) | 2001-10-22 | 2004-11-30 | Penjet Corporation | Engine and diffuser for use with a needle-less injector |
CA2466982A1 (en) * | 2001-11-19 | 2003-05-30 | Becton, Dickinson And Company | Pharmaceutical compositions in particulate form |
US20050176084A1 (en) | 2001-12-17 | 2005-08-11 | Burkoth Terry L. | Non-or minimally invasive monitoring methods |
US8454997B2 (en) | 2001-12-18 | 2013-06-04 | Novo Nordisk A/S | Solid dose micro implant |
US7368102B2 (en) | 2001-12-19 | 2008-05-06 | Nektar Therapeutics | Pulmonary delivery of aminoglycosides |
DE20209051U1 (de) | 2001-12-21 | 2003-04-24 | Disetronic Licensing Ag | Injektionsgerät mit endpositionsblockiertem Dosiseinstellglied |
US20030130614A1 (en) * | 2002-01-09 | 2003-07-10 | Johnson Lanny L. | Device for delivering liquid medications or nutrients and gases to local tissue |
EP1476209B1 (en) | 2002-02-18 | 2008-07-30 | Danfoss A/S | Device for administering of medication in fluid form |
US20030163111A1 (en) * | 2002-02-26 | 2003-08-28 | Daellenbach Keith K. | End effector for needle-free injection system |
CA2380671A1 (fr) * | 2002-04-05 | 2003-10-05 | Stephane Dufresne | Seringue sans aiguille pour l'injection sous-cutanee de gouttelettes medicamenteuses |
EP1356820A1 (en) | 2002-04-26 | 2003-10-29 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | DNA vaccine combined with an inducer of tumor cell apoptosis |
US7334580B2 (en) * | 2002-05-07 | 2008-02-26 | Smaldone Gerald C | Methods, devices and formulations for targeted endobronchial therapy |
US7607436B2 (en) * | 2002-05-06 | 2009-10-27 | The Research Foundation Of State University Of New York | Methods, devices and formulations for targeted endobronchial therapy |
US7156823B2 (en) * | 2002-06-04 | 2007-01-02 | Bioject Inc. | High workload needle-free injection system |
GB0212885D0 (en) | 2002-06-05 | 2002-07-17 | Isis Innovation | Therapeutic epitopes and uses thereof |
EA010881B1 (ru) * | 2002-09-27 | 2008-12-30 | Паудерджект Рисерч Лимитед | Частицы, покрытые нуклеиновой кислотой |
AU2003282683A1 (en) * | 2002-10-04 | 2004-05-04 | Photokinetix Inc. | Photokinetic delivery of biologically active substances using pulsed incoherent light |
ATE474613T1 (de) * | 2003-02-03 | 2010-08-15 | Bioware Technology Co Ltd | Genpistole mit niederdruckgasbeschleunigung |
DE10306716A1 (de) * | 2003-02-17 | 2004-09-02 | Lell, Peter, Dr.-Ing. | Vorrichtung zum Injizieren eines staub-oder pulverförmigen Stoffs in ein Gewebe eines Körpers |
MXPA05010221A (es) | 2003-03-25 | 2006-02-22 | Terry O Herndon | Dispositivo y metodo de taladrado para formar microconductos. |
DE10316237A1 (de) * | 2003-04-09 | 2004-11-04 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Kanüle und Verfahren zur Einführung einer Kanüle in biologisches Material |
US20040260234A1 (en) * | 2003-04-21 | 2004-12-23 | Ravi Srinivasan | Apparatus and methods for repetitive microjet durg delivery priority statement |
US20060184101A1 (en) * | 2003-04-21 | 2006-08-17 | Ravi Srinivasan | Microjet devices and methods for drug delivery |
US20070066935A1 (en) * | 2003-05-09 | 2007-03-22 | Ryuichi Morishita | Needleless syringe having medical agent accomodated therein |
EA012783B1 (ru) | 2003-06-13 | 2009-12-30 | Джон Клод Савуар | Фармацевтическая композиция для контрацепции и заместительной гормональной терапии |
US7131961B2 (en) * | 2003-10-01 | 2006-11-07 | Bioject, Inc. | Needle-free injection system |
PL1685251T3 (pl) * | 2003-10-10 | 2014-07-31 | Powderject Vaccines Inc | Konstrukty kwasu nukleinowego |
US7442182B2 (en) * | 2003-10-24 | 2008-10-28 | Bioject, Inc. | Spring powered needle-free injection system |
US8147426B2 (en) * | 2003-12-31 | 2012-04-03 | Nipro Diagnostics, Inc. | Integrated diagnostic test system |
US20050209553A1 (en) * | 2004-03-19 | 2005-09-22 | Sergio Landau | Needle-free single-use cartridge and injection system |
US20050209554A1 (en) * | 2004-03-19 | 2005-09-22 | Sergio Landau | Needle-free single-use cartridge and injection system |
JP4210231B2 (ja) * | 2004-03-25 | 2009-01-14 | 株式会社資生堂 | 皮膚のシワを改善する美容方法及びシワ改善具 |
US7456254B2 (en) * | 2004-04-15 | 2008-11-25 | Alkermes, Inc. | Polymer-based sustained release device |
KR101040415B1 (ko) * | 2004-04-15 | 2011-06-09 | 알케르메스,인코포레이티드 | 중합체 기재 지속적 방출 방법 |
US20060110423A1 (en) * | 2004-04-15 | 2006-05-25 | Wright Steven G | Polymer-based sustained release device |
CN104056251B (zh) | 2004-04-28 | 2019-09-17 | 英国技术集团国际有限公司 | 与腹部疾病有关的表位 |
US10105437B2 (en) | 2004-04-28 | 2018-10-23 | Btg International Limited | Epitopes related to coeliac disease |
PT1758558E (pt) | 2004-05-12 | 2013-12-05 | Baxter Healthcare Sa | Microesferas contendo oligonucleótidos, sua utilização para o fabrico de um medicamento para o tratamento de diabetes do tipo 1 |
WO2005112894A1 (en) | 2004-05-12 | 2005-12-01 | Baxter International Inc. | Nucleic acid microspheres, production and delivery thereof |
US7717874B2 (en) * | 2004-05-28 | 2010-05-18 | Bioject, Inc. | Needle-free injection system |
US20060038044A1 (en) * | 2004-08-23 | 2006-02-23 | Van Steenkiste Thomas H | Replaceable throat insert for a kinetic spray nozzle |
US20060089594A1 (en) * | 2004-10-26 | 2006-04-27 | Sergio Landau | Needle-free injection device |
US20060089593A1 (en) * | 2004-10-26 | 2006-04-27 | Sergio Landau | Needle-free injection device for individual users |
NZ556186A (en) | 2004-12-01 | 2010-06-25 | Acushot Inc | Needle-free injector |
WO2006074166A2 (en) * | 2005-01-06 | 2006-07-13 | Benitec, Inc. | Rnai agents for maintenance of stem cells |
GB0507997D0 (en) * | 2005-02-01 | 2005-05-25 | Powderject Vaccines Inc | Nucleic acid constructs |
US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
WO2006091459A2 (en) * | 2005-02-24 | 2006-08-31 | Joslin Diabetes Center, Inc. | Compositions and methods for treating vascular permeability |
DE102005015801A1 (de) | 2005-04-06 | 2006-10-19 | Schreiner Group Gmbh & Co. Kg | Folienbasierter Schutzmechanismus |
US20070118093A1 (en) * | 2005-06-20 | 2007-05-24 | Von Muhlen Marcio G | High-speed jet devices for drug delivery |
US20070055200A1 (en) * | 2005-08-10 | 2007-03-08 | Gilbert Scott J | Needle-free jet injection drug delivery device |
CA2620943A1 (en) * | 2005-09-02 | 2007-03-08 | Iomai Corporation | Devices for transcutaneous delivery of vaccines and transdermal delivery of drugs and uses thereof |
WO2007073527A2 (en) * | 2005-11-29 | 2007-06-28 | Mitchell Stuart B | Electrostatic transcutaneous hypodermic spray (electrostatic hypospray) |
JP4402648B2 (ja) | 2005-12-16 | 2010-01-20 | オリンパス株式会社 | 被検体内導入装置 |
US20080161755A1 (en) * | 2006-01-27 | 2008-07-03 | Bioject Inc. | Needle-free injection device and priming system |
EP1981568B1 (en) | 2006-01-31 | 2013-08-14 | Novo Nordisk A/S | Seal for a prefilled medical jet injection device |
GB0611443D0 (en) * | 2006-06-09 | 2006-07-19 | Powderject Res Ltd | Improvements in, or relating to, particle cassettes |
WO2008021133A2 (en) | 2006-08-09 | 2008-02-21 | Intarcia Therapeutics, Inc. | Osmotic delivery systems and piston assemblies |
CN100446823C (zh) * | 2006-09-19 | 2008-12-31 | 宁波新芝生物科技股份有限公司 | 一种无创介入治疗系统 |
US7547293B2 (en) | 2006-10-06 | 2009-06-16 | Bioject, Inc. | Triggering mechanism for needle-free injector |
US9017697B2 (en) | 2006-10-12 | 2015-04-28 | The University Of Queensland | Compositions and methods for modulating immune responses |
FR2908753B1 (fr) * | 2006-11-16 | 2011-11-11 | Becton Dickinson France | Dispositif pour delivrer automatiquement des doses successives de produit |
DE102007004855B4 (de) * | 2007-01-31 | 2014-03-27 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Vorrichtung und Verfahren zur Deposition von biologischem Material in einem Zielsubstrat |
JP2008199905A (ja) * | 2007-02-16 | 2008-09-04 | Snow Brand Milk Prod Co Ltd | 乳酸菌生残性向上剤 |
WO2008103997A2 (en) * | 2007-02-23 | 2008-08-28 | Bioject Inc. | Needle-free injection devices and drug delivery systems therefor |
NZ580447A (en) | 2007-04-23 | 2011-06-30 | Intarcia Therapeutics Inc | Suspension formulations of insulinotropic peptides and uses thereof |
GB0708758D0 (en) * | 2007-05-04 | 2007-06-13 | Powderject Res Ltd | Particle cassettes and process thereof |
CN101754682B (zh) | 2007-05-16 | 2014-11-12 | 布里格姆妇女医院 | 突触核蛋白病的治疗 |
GB2449312B (en) | 2007-05-18 | 2012-03-14 | Malvern Instr Ltd | Method and apparatus for dispersing a sample of particulate material |
JP4780034B2 (ja) * | 2007-05-18 | 2011-09-28 | 株式会社島津製作所 | 針無注射器 |
KR101383476B1 (ko) | 2007-11-01 | 2014-04-11 | 아스테라스 세이야쿠 가부시키가이샤 | 면역억제 폴리펩티드 및 핵산 |
US8343140B2 (en) | 2008-02-13 | 2013-01-01 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
US20110117673A1 (en) * | 2008-07-16 | 2011-05-19 | Johnson Brandon T | Methods and systems to collect and prepare samples, to implement, initiate and perform assays, and to control and manage fluid flow |
US8021873B2 (en) | 2008-07-16 | 2011-09-20 | Boston Microfluidics | Portable, point-of-care, user-initiated fluidic assay methods and systems |
EP2385371B1 (en) | 2008-09-22 | 2014-10-22 | Oregon Health and Science University | Methods for detecting a mycobacterium tuberculosis infection |
DE102008048981A1 (de) * | 2008-09-25 | 2010-04-15 | Lts Lohmann Therapie-Systeme Ag | Injektor und Zwei-Kammer-System mit sterilen Komponenten |
US9207242B2 (en) | 2008-10-09 | 2015-12-08 | The University Of Hong Kong | Cadherin-17 as diagnostic marker and therapeutic target for liver cancer |
US8731841B2 (en) * | 2008-10-31 | 2014-05-20 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
US8725420B2 (en) | 2008-10-31 | 2014-05-13 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
US20100111834A1 (en) * | 2008-10-31 | 2010-05-06 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Compositions and methods for therapeutic delivery with frozen particles |
US9060926B2 (en) * | 2008-10-31 | 2015-06-23 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
US8793075B2 (en) | 2008-10-31 | 2014-07-29 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
US20100111857A1 (en) | 2008-10-31 | 2010-05-06 | Boyden Edward S | Compositions and methods for surface abrasion with frozen particles |
US9050317B2 (en) | 2008-10-31 | 2015-06-09 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
US8762067B2 (en) * | 2008-10-31 | 2014-06-24 | The Invention Science Fund I, Llc | Methods and systems for ablation or abrasion with frozen particles and comparing tissue surface ablation or abrasion data to clinical outcome data |
US8731840B2 (en) | 2008-10-31 | 2014-05-20 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
US9072688B2 (en) * | 2008-10-31 | 2015-07-07 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
US9072799B2 (en) | 2008-10-31 | 2015-07-07 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
US8409376B2 (en) | 2008-10-31 | 2013-04-02 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
US8551505B2 (en) * | 2008-10-31 | 2013-10-08 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
US9050070B2 (en) | 2008-10-31 | 2015-06-09 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
US8721583B2 (en) | 2008-10-31 | 2014-05-13 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
US8788211B2 (en) * | 2008-10-31 | 2014-07-22 | The Invention Science Fund I, Llc | Method and system for comparing tissue ablation or abrasion data to data related to administration of a frozen particle composition |
US9060934B2 (en) | 2008-10-31 | 2015-06-23 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
US8545855B2 (en) * | 2008-10-31 | 2013-10-01 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
US8232093B2 (en) | 2009-02-05 | 2012-07-31 | Indian Institute Of Science | Apparatus and method for genetically transforming cells |
WO2010104858A2 (en) * | 2009-03-09 | 2010-09-16 | Purdue Research Foundation | Compact device for rapidly mixing and delivering substances to a patient |
WO2010105096A2 (en) | 2009-03-11 | 2010-09-16 | University Of Massachusetts | Modulation of human cytomegalovirus replication by micro-rna 132 (mir132), micro-rna 145 (mir145) and micro-rna 212 (mir212) |
EP2411519B1 (en) | 2009-03-27 | 2015-07-22 | Institut National de la Santé et de la Recherche Médicale | Kanamycin antisense nucleic acid for the treatment of cancer |
EP2756845B1 (en) | 2009-04-03 | 2017-03-15 | Dicerna Pharmaceuticals, Inc. | Methods and compositions for the specific inhibition of KRAS by asymmetric double-stranded RNA |
GB0906215D0 (en) | 2009-04-09 | 2009-05-20 | Lalvani Ajit | Diagnostic test |
TWI439302B (zh) | 2009-07-14 | 2014-06-01 | Chien Lung Chen | 傳輸裝置 |
CN101987218B (zh) * | 2009-07-30 | 2013-07-10 | 陈建龙 | 传输装置 |
NZ624569A (en) | 2009-09-28 | 2016-01-29 | Intarcia Therapeutics Inc | Rapid establishment and/or termination of substantial steady-state drug delivery |
EP2942060A1 (en) | 2009-09-29 | 2015-11-11 | Joslin Diabetes Center, Inc. | Use of Protein Kinase C Delta (PKCD) Inhibitors to Treat Diabetes, Obesity and, Hepatic Steatosis |
EP3360566B1 (en) | 2009-11-20 | 2019-12-25 | Oregon Health&Science University | Methods for detecting a mycobacterium tuberculosis infection |
EP2501433A1 (en) * | 2009-11-20 | 2012-09-26 | Talima Therapeutics, Inc. | Devices for implanting compositions and methods and kits therefor |
CN201888971U (zh) * | 2010-01-08 | 2011-07-06 | 江苏华兰米特医疗科技有限公司 | 无针注射器 |
EP2533814A2 (en) | 2010-02-11 | 2012-12-19 | Ablynx N.V. | Delivery of immunoglobulin variable domains and constructs thereof |
WO2011123762A1 (en) * | 2010-04-01 | 2011-10-06 | Glucago Llc | Method and device for mixing substances |
EP2576613A1 (en) | 2010-06-07 | 2013-04-10 | Pfizer Inc. | Her-2 peptides and vaccines |
JP5934710B2 (ja) * | 2010-10-07 | 2016-06-15 | マサチューセッツ インスティテュート オブ テクノロジー | ローレンツ力直動型の無針式ジェット注射システムを用いた固形物および/または流体の供給 |
US9211378B2 (en) | 2010-10-22 | 2015-12-15 | Cequr Sa | Methods and systems for dosing a medicament |
EP2635596B8 (en) | 2010-11-01 | 2020-03-11 | University of Technology Sydney | Immune-modulating agents and uses therefor |
GB201021881D0 (en) * | 2010-12-23 | 2011-02-02 | Profibrix Bv | Powder delivery device |
US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
US8486002B2 (en) | 2011-04-19 | 2013-07-16 | Palo Alto Research Center Incorporated | Drug delivery devices and methods with collimated gas stream and release-activatable tape |
US8388569B2 (en) | 2011-04-19 | 2013-03-05 | Xerox Corporation | Delivery devices and methods with collimated gas stream and particle source |
US8430839B2 (en) | 2011-04-19 | 2013-04-30 | Palo Alto Research Center Incorporated | Drug delivery devices and methods with collimated gas stream and drug reservoir |
ES2490915B1 (es) | 2011-09-12 | 2015-09-17 | Laboratorios Del Dr. Esteve, S.A. | Método para monitorizar las respuestas de linfocitos T citotóxicos (LTC) mediante una reacción de hipersensibilidad de tipo retardado usando epítopos de LTC definidos |
EP2780456A1 (en) | 2011-11-17 | 2014-09-24 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Therapeutic rna switches compositions and methods of use |
US20140058319A1 (en) * | 2012-03-20 | 2014-02-27 | Glucago Llc | Compact Device For Rapidly Mixing and Delivering Substances To a Patient |
US8992469B2 (en) | 2012-06-26 | 2015-03-31 | Glucago Llc | Reconstitution device |
US9125995B2 (en) | 2012-12-05 | 2015-09-08 | Glucago Llc | Reconstitution devices |
US9345487B2 (en) | 2013-02-05 | 2016-05-24 | Path Scientific, Llc | Precision bone drill and method of use |
EP2851086A1 (en) | 2013-09-20 | 2015-03-25 | Sanofi | Serpins: methods of therapeutic ß-cell regeneration and function |
EP2769732A1 (en) | 2013-02-22 | 2014-08-27 | Sanofi | Serpins: methods of therapeutic beta-cell regeneration and function |
WO2014128257A1 (en) | 2013-02-22 | 2014-08-28 | Sanofi | Serpins: methods of therapeutic beta-cell regeneration and function |
EP2968886A1 (en) | 2013-03-14 | 2016-01-20 | Hallux, Inc. | Method of treating infections, diseases or disorders of nail unit |
US9808579B2 (en) * | 2013-05-08 | 2017-11-07 | Elwha Llc | Needleless injector systems, and related methods and components |
US10279113B2 (en) * | 2013-05-17 | 2019-05-07 | Socpra Sciences Et Genie S.E.C. | Needleless syringe and method for delivering therapeutic particles |
JP6369551B2 (ja) | 2014-02-26 | 2018-08-08 | パウダー ファーマシューティカルズ インコーポレイテッド | 粒子を送達する装置 |
WO2015171964A1 (en) * | 2014-05-07 | 2015-11-12 | Sri International | Needle free injection device |
US9737251B2 (en) | 2014-05-28 | 2017-08-22 | Verily Life Sciences Llc | Needle-free blood draw |
EP2959931A1 (de) * | 2014-06-24 | 2015-12-30 | LTS LOHMANN Therapie-Systeme AG | Nadellose Injektionsvorrichtung |
US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
EP3011988A1 (de) * | 2014-10-22 | 2016-04-27 | LTS LOHMANN Therapie-Systeme AG | Nadellose Injektionsvorrichtung aufweisend ein Gel und eine Membran |
US10420826B2 (en) | 2014-11-11 | 2019-09-24 | Massachusetts Eye & Ear Infirmary | Conjunctivitis vaccines |
ES2747842T3 (es) | 2014-12-15 | 2020-03-11 | Dicerna Pharmaceuticals Inc | Acidos nucleicos de doble hebra modificados por ligando |
ES2901455T3 (es) | 2015-04-03 | 2022-03-22 | Univ Massachusetts | Compuestos oligonucleotídicos para el tratamiento de preeclampsia y otros trastornos angiogénicos |
WO2016161374A1 (en) | 2015-04-03 | 2016-10-06 | University Of Massachusetts | Oligonucleotide compounds for targeting huntingtin mrna |
WO2016179497A1 (en) | 2015-05-07 | 2016-11-10 | Shire Human Genetic Therapies, Inc. | Glucocerebrosidase gene therapy for parkinson's disease |
MX2017015504A (es) | 2015-06-03 | 2018-05-15 | Intarcia Therapeutics Inc | Sistemas de colocacion y remoción de implante. |
US20160361240A1 (en) | 2015-06-11 | 2016-12-15 | The Procter & Gamble Company | Apparatus and methods for modifying keratinous surfaces |
US10633653B2 (en) | 2015-08-14 | 2020-04-28 | University Of Massachusetts | Bioactive conjugates for oligonucleotide delivery |
JP2018535655A (ja) | 2015-09-29 | 2018-12-06 | アムジエン・インコーポレーテツド | Asgr阻害剤 |
US11001622B2 (en) | 2015-11-19 | 2021-05-11 | The Brigham And Women's Hospital, Inc. | Method of treating autoimmune disease with lymphocyte antigen CD5-like (CD5L) protein |
JP7088843B2 (ja) * | 2015-12-28 | 2022-06-21 | イノビオ ファーマシューティカルズ,インコーポレイティド | 皮内ジェット注射式電気穿孔装置 |
JP2019503394A (ja) | 2016-01-31 | 2019-02-07 | ユニバーシティ・オブ・マサチューセッツUniversity Of Massachusetts | 分岐オリゴヌクレオチド |
SG11201810102SA (en) | 2016-05-16 | 2018-12-28 | Intarcia Therapeutics Inc | Glucagon-receptor selective polypeptides and methods of use thereof |
USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
EP3496758A4 (en) | 2016-08-12 | 2020-11-11 | University of Massachusetts | CONJUGATE OLIGONUCLEOTIDES |
US10443055B2 (en) | 2016-12-22 | 2019-10-15 | Beth Israel Deaconess Medical Center | Compounds that target MYC microRNA responsive elements for the treatment of MYC-associated cancer |
IL307966A (en) | 2017-01-03 | 2023-12-01 | Intarcia Therapeutics Inc | Methods involving continuous administration of a GLP-1 receptor agonist and co-administration of a drug |
US20210128702A1 (en) | 2017-08-11 | 2021-05-06 | Dana-Farber Cancer Institute, Inc. | Use of a botulinum toxin agent for treating plasma cell disorders |
WO2019036375A1 (en) | 2017-08-14 | 2019-02-21 | Sanford Burnham Prebys Medical Discovery Institute | CARDIOGENIC MESODERMA TRAINING REGULATORS |
US11413288B2 (en) | 2017-11-01 | 2022-08-16 | Dana-Farber Cancer Institute, Inc. | Methods of treating cancers |
CN108553748A (zh) * | 2018-05-11 | 2018-09-21 | 江秀秀 | B超监视下体内多种细胞植入仪 |
CA3098266A1 (en) | 2018-05-11 | 2019-11-14 | Alpha Anomeric Sas | Oligonucleotides conjugates comprising 7'-5'-alpha-anomeric-bicyclic sugar nucleosides |
USD933219S1 (en) | 2018-07-13 | 2021-10-12 | Intarcia Therapeutics, Inc. | Implant removal tool and assembly |
EP3833763A4 (en) | 2018-08-10 | 2023-07-19 | University of Massachusetts | MODIFIED OLIGONUCLEOTIDES TARGETING SNPs |
EP3843845A4 (en) | 2018-08-29 | 2022-05-11 | University Of Massachusetts | INHIBITION OF PROTEIN KINASE FOR THE TREATMENT OF FRIEDREICH'S ATAXIA |
KR102199724B1 (ko) * | 2018-10-05 | 2021-01-07 | 주식회사 피테크 | 무바늘 무통 주사 장치 |
CA3177829A1 (en) | 2018-12-12 | 2020-06-18 | Kite Pharma, Inc. | Chimeric antigen and t cell receptors and methods of use |
US11629347B2 (en) | 2019-05-06 | 2023-04-18 | University Of Massachusetts | Anti-C9ORF72 oligonucleotides and related methods |
IT201900007060A1 (it) | 2019-05-21 | 2020-11-21 | St Superiore Di Sanita | Cellule tumorali ingegnerizzate e loro usi |
CN110038212A (zh) * | 2019-05-29 | 2019-07-23 | 徐小棠 | 一种呼吸内科护理给药多用装置 |
CN110180051B (zh) * | 2019-07-13 | 2021-04-02 | 河南省中医院(河南中医药大学第二附属医院) | 产科护理用清洗装置 |
IT201900012540A1 (it) | 2019-07-22 | 2021-01-22 | Humanitas Mirasole Spa | Inibitori di CHI3L1 e loro usi |
GB202105455D0 (en) | 2021-04-16 | 2021-06-02 | Ucl Business Ltd | Composition |
AU2022299169A1 (en) | 2021-06-23 | 2024-02-08 | Beth Israel Deaconess Medical Center, Inc. | Optimized anti-flt1 oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders |
WO2022269570A1 (en) * | 2021-06-24 | 2022-12-29 | Avectas Limited | Spray nozzle |
GB202112471D0 (en) | 2021-09-01 | 2021-10-13 | King S College London | Microna systems |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3788315A (en) * | 1971-04-20 | 1974-01-29 | S Laurens | Disposable cutaneous transjector |
WO1992004439A1 (en) * | 1990-08-30 | 1992-03-19 | Brian John Bellhouse | Ballistic apparatus |
Family Cites Families (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE170094C (zh) | ||||
US1300654A (en) | 1919-01-30 | 1919-04-15 | William H Rose | Dry-spraying machine. |
US2151418A (en) * | 1937-05-12 | 1939-03-21 | Scott & Bowne | Powder applicator |
US2147158A (en) | 1937-09-28 | 1939-02-14 | Goldenthal Philip | Powder insufflator |
US2307986A (en) | 1940-02-15 | 1943-01-12 | Bolte | Insufflator |
US2605763A (en) * | 1948-01-31 | 1952-08-05 | Becton Dickinson Co | Injection device |
GB677523A (en) * | 1948-04-13 | 1952-08-20 | Becton Dickinson Co | Discharge structure for hypodermic injection device |
US2478715A (en) | 1948-07-14 | 1949-08-09 | Vilbiss Co | Powder blower |
US2594093A (en) | 1949-02-05 | 1952-04-22 | Armour & Co | Powder container |
US2470298A (en) | 1949-02-07 | 1949-05-17 | Abbott Lab | Powdered medicine dispenser |
DE1047385B (de) * | 1952-03-08 | 1958-12-24 | Armour & Co | Puderzerstaeuber mit einem auswechselbaren Puderbehaelter |
US3216562A (en) | 1963-06-13 | 1965-11-09 | Driaire Inc | Easy-open capsule |
IL28680A (en) | 1966-12-16 | 1971-12-29 | American Home Prod | Stabilized aqueous suspensions of benzathine penicillin |
US3674028A (en) * | 1969-06-04 | 1972-07-04 | Ims Ltd | Multi-mix |
US3736933A (en) * | 1970-12-02 | 1973-06-05 | B Szabo | Burstable seamed hypodermic applicators |
US3914573A (en) * | 1971-05-17 | 1975-10-21 | Geotel Inc | Coating heat softened particles by projection in a plasma stream of Mach 1 to Mach 3 velocity |
US3853125A (en) * | 1971-10-05 | 1974-12-10 | W Clark | Disposable needleless injector |
US3782380A (en) * | 1973-01-04 | 1974-01-01 | Gaast H V D | Medicament injecting device |
US4069819A (en) * | 1973-04-13 | 1978-01-24 | Societa Farmaceutici S.P.A. | Inhalation device |
US3946732A (en) * | 1973-08-08 | 1976-03-30 | Ampoules, Inc. | Two-chamber mixing syringe |
US3967761A (en) | 1974-04-08 | 1976-07-06 | Southwest Research Institute | System for injecting particulate material into the combustion chamber of a repetitive combustion coating apparatus |
US3952741A (en) * | 1975-01-09 | 1976-04-27 | Bend Research Inc. | Controlled release delivery system by an osmotic bursting mechanism |
US3982605A (en) * | 1975-05-05 | 1976-09-28 | The Carborundum Company | Nozzle noise silencer |
FR2360031A1 (fr) * | 1976-07-27 | 1978-02-24 | Klein Max | Dispositif distributeur silencieux d'un jet de gaz et application au diagnostic medical |
JPS602489B2 (ja) * | 1977-05-02 | 1985-01-22 | 株式会社豊田中央研究所 | 低騒音用圧力流体放出装置 |
JPS557272A (en) * | 1978-06-16 | 1980-01-19 | Rech Pharma Sa | Drug composition containing urea |
US4226236A (en) * | 1979-05-07 | 1980-10-07 | Abbott Laboratories | Prefilled, vented two-compartment syringe |
US4778054A (en) | 1982-10-08 | 1988-10-18 | Glaxo Group Limited | Pack for administering medicaments to patients |
AU570013B2 (en) | 1982-10-08 | 1988-03-03 | Glaxo Group Limited | Medicament inhaler |
US4515586A (en) | 1982-11-30 | 1985-05-07 | Abbott Laboratories | Powder syringe mixing system |
US4652261A (en) * | 1984-06-22 | 1987-03-24 | Regents Of The University Of Minnesota | Drug-injection animal capture collar |
US4945050A (en) * | 1984-11-13 | 1990-07-31 | Cornell Research Foundation, Inc. | Method for transporting substances into living cells and tissues and apparatus therefor |
US5100792A (en) * | 1984-11-13 | 1992-03-31 | Cornell Research Foundation, Inc. | Method for transporting substances into living cells and tissues |
US5036006A (en) * | 1984-11-13 | 1991-07-30 | Cornell Research Foundation, Inc. | Method for transporting substances into living cells and tissues and apparatus therefor |
US4596556A (en) * | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
DK163640C (da) | 1985-07-30 | 1992-08-17 | Glaxo Group Ltd | Apparat til administrering af medikamenter |
DK179286D0 (da) | 1986-04-18 | 1986-04-18 | Nordisk Gentofte | Insulinpraeparat |
USRE33801E (en) | 1986-05-09 | 1992-01-21 | Dentsply Research & Development Corp. | Mixing and discharge capsule |
US5120657A (en) | 1986-12-05 | 1992-06-09 | Agracetus, Inc. | Apparatus for genetic transformation |
IN170021B (zh) * | 1987-05-26 | 1992-01-25 | Deita Freyberg Gmbh | |
GB2206794A (en) * | 1987-07-14 | 1989-01-18 | Richard Kiteley Power | Syringe |
US4853229A (en) * | 1987-10-26 | 1989-08-01 | Alza Corporation | Method for adminstering tiny pills |
US5179022A (en) * | 1988-02-29 | 1993-01-12 | E. I. Du Pont De Nemours & Co. | Biolistic apparatus for delivering substances into cells and tissues in a non-lethal manner |
BR8801952A (pt) * | 1988-04-22 | 1989-11-14 | Sergio Landau | Capsula descartavel,nao re-utilizavel,contendo dose individual de vacina a ser injetada hipodermicamente,sem agulha,com aparelho injetor a pressao |
FR2638359A1 (fr) * | 1988-11-03 | 1990-05-04 | Tino Dalto | Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau |
ATE120762T1 (de) * | 1989-04-20 | 1995-04-15 | Sinai School Medicine | Hepatospezifische insulin-analoga. |
US5239991A (en) | 1989-06-21 | 1993-08-31 | Fisons Plc | Disposable powder medicament inhalation device with peel-off cover |
HU200699B (en) * | 1989-07-05 | 1990-08-28 | Gyula Erdelyi | Neddleless hypodermic syringe particularly for blinds and poor-sighted persons |
GB8918879D0 (en) * | 1989-08-18 | 1989-09-27 | Danbiosyst Uk | Pharmaceutical compositions |
US5064413A (en) * | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
AU7558991A (en) * | 1990-03-15 | 1991-10-10 | United States Of America, As Represented By The Secretary Of The Army, The | Chemotherapeutic treatment of bacterial infections with an antibiotic encapsulated within a biodegradable polymeric matrix |
US5062830A (en) * | 1990-04-04 | 1991-11-05 | Derata Corporation | Dry disposable nozzle assembly for medical jet injector |
GB9011588D0 (en) * | 1990-05-24 | 1990-07-11 | Wellcome Found | Prostaglandin analogues for use in medicine |
US5204253A (en) * | 1990-05-29 | 1993-04-20 | E. I. Du Pont De Nemours And Company | Method and apparatus for introducing biological substances into living cells |
US5149655A (en) * | 1990-06-21 | 1992-09-22 | Agracetus, Inc. | Apparatus for genetic transformation |
IT1243344B (it) | 1990-07-16 | 1994-06-10 | Promo Pack Sa | Inalatore plurimonodose per medicamenti in polvere |
GB9016789D0 (en) * | 1990-07-31 | 1990-09-12 | Lilly Industries Ltd | Medicament administering devices |
US5042472A (en) | 1990-10-15 | 1991-08-27 | Merck & Co., Inc. | Powder inhaler device |
US5046618A (en) | 1990-11-19 | 1991-09-10 | R. P. Scherer Corporation | Child-resistant blister pack |
US5188615A (en) | 1990-11-19 | 1993-02-23 | Habley Medical Technology Corp. | Mixing vial |
DK288590D0 (da) * | 1990-12-04 | 1990-12-04 | Michael Morris | Blandings/oploesnings-sproejte til cytostatika for medicinsk behandling af cancer patienter |
GB9027422D0 (en) * | 1990-12-18 | 1991-02-06 | Scras | Osmotically driven infusion device |
US5360410A (en) | 1991-01-16 | 1994-11-01 | Senetek Plc | Safety syringe for mixing two-component medicaments |
GB9100950D0 (en) * | 1991-01-16 | 1991-02-27 | Dunne Miller Weston Ltd | Metered dose atomising and delivery device |
US5492112A (en) | 1991-05-20 | 1996-02-20 | Dura Pharmaceuticals, Inc. | Dry powder inhaler |
US5102388A (en) | 1991-07-15 | 1992-04-07 | Richmond John E | Sequential delivery syringe |
GB9118204D0 (en) * | 1991-08-23 | 1991-10-09 | Weston Terence E | Needle-less injector |
EP0558879B1 (en) | 1992-03-04 | 1997-05-14 | Astra Aktiebolag | Disposable inhaler |
EP0659150B1 (en) | 1992-09-09 | 1997-05-21 | FISONS plc | Pharmaceutical packaging |
TW404844B (en) * | 1993-04-08 | 2000-09-11 | Oxford Biosciences Ltd | Needleless syringe |
US5349947A (en) * | 1993-07-15 | 1994-09-27 | Newhouse Michael T | Dry powder inhaler and process that explosively discharges a dose of powder and gas from a soft plastic pillow |
US5415162A (en) | 1994-01-18 | 1995-05-16 | Glaxo Inc. | Multi-dose dry powder inhalation device |
ES2247248T3 (es) | 1994-01-21 | 2006-03-01 | Powderject Vaccines, Inc. | Instrumento de administracion de genes movido por gas comprimido. |
US5483954A (en) | 1994-06-10 | 1996-01-16 | Mecikalski; Mark B. | Inhaler and medicated package |
JP3320261B2 (ja) * | 1995-06-01 | 2002-09-03 | 株式会社ユニシアジェックス | 吸入式投薬器 |
-
1994
- 1994-04-07 TW TW083103025A patent/TW404844B/zh not_active IP Right Cessation
- 1994-04-07 TW TW086113385A patent/TW360548B/zh not_active IP Right Cessation
- 1994-04-08 NZ NZ263606A patent/NZ263606A/xx not_active IP Right Cessation
- 1994-04-08 HU HU9802714A patent/HU228144B1/hu unknown
- 1994-04-08 PT PT96109925T patent/PT734737E/pt unknown
- 1994-04-08 TJ TJ95000044A patent/TJ248B/xx unknown
- 1994-04-08 PL PL94311005A patent/PL174974B1/pl unknown
- 1994-04-08 DE DE69401651T patent/DE69401651T2/de not_active Expired - Lifetime
- 1994-04-08 RO RO95-01747A patent/RO118569B1/ro unknown
- 1994-04-08 WO PCT/GB1994/000753 patent/WO1994024263A1/en active IP Right Grant
- 1994-04-08 CZ CZ19952608A patent/CZ290476B6/cs not_active IP Right Cessation
- 1994-04-08 AT AT96109925T patent/ATE329006T1/de active
- 1994-04-08 KR KR1019950704408A patent/KR100332147B1/ko not_active IP Right Cessation
- 1994-04-08 ES ES94912038T patent/ES2098131T3/es not_active Expired - Lifetime
- 1994-04-08 EP EP05028150.0A patent/EP1637173B1/en not_active Expired - Lifetime
- 1994-04-08 SK SK1248-95A patent/SK283855B6/sk not_active IP Right Cessation
- 1994-04-08 UA UA95094347A patent/UA41360C2/uk unknown
- 1994-04-08 EP EP99113305A patent/EP0951917A3/en not_active Withdrawn
- 1994-04-08 BR BR9406455A patent/BR9406455A/pt not_active Application Discontinuation
- 1994-04-08 AT AT94912038T patent/ATE148497T1/de active
- 1994-04-08 DK DK96109925T patent/DK0734737T3/da active
- 1994-04-08 CA CA002159452A patent/CA2159452C/en not_active Expired - Lifetime
- 1994-04-08 DE DE69434760T patent/DE69434760T2/de not_active Expired - Lifetime
- 1994-04-08 JP JP52287794A patent/JP3260375B2/ja not_active Expired - Lifetime
- 1994-04-08 EP EP94912038A patent/EP0693119B1/en not_active Expired - Lifetime
- 1994-04-08 AU AU64351/94A patent/AU674742B2/en not_active Expired
- 1994-04-08 SI SI9430045T patent/SI0693119T1/xx unknown
- 1994-04-08 CN CN94191721A patent/CN1109102C/zh not_active Expired - Lifetime
- 1994-04-08 RU RU95119388A patent/RU2129021C1/ru active
- 1994-04-08 SI SI9430481T patent/SI0734737T1/sl unknown
- 1994-04-08 DK DK94912038.0T patent/DK0693119T3/da active
- 1994-04-08 ES ES96109925T patent/ES2267106T3/es not_active Expired - Lifetime
- 1994-04-08 HU HU9502911A patent/HU216308B/hu unknown
- 1994-04-08 EP EP96109925A patent/EP0734737B1/en not_active Expired - Lifetime
-
1995
- 1995-06-07 US US08/474,367 patent/US5630796A/en not_active Expired - Lifetime
- 1995-10-04 BG BG100047A patent/BG61993B1/bg unknown
- 1995-10-06 OA OA60719A patent/OA10234A/en unknown
- 1995-10-06 FI FI954788A patent/FI120671B/fi not_active IP Right Cessation
- 1995-10-06 NO NO19953994A patent/NO314570B1/no not_active IP Right Cessation
-
1997
- 1997-03-17 LV LVP-97-41A patent/LV11833B/en unknown
- 1997-03-26 GR GR970400626T patent/GR3022939T3/el unknown
- 1997-10-09 HK HK97101908A patent/HK1000351A1/xx not_active IP Right Cessation
- 1997-12-05 US US08/986,124 patent/US6168587B1/en not_active Expired - Lifetime
-
1999
- 1999-02-10 US US09/248,743 patent/US6881200B2/en not_active Expired - Lifetime
-
2001
- 2001-09-27 JP JP2001298589A patent/JP2002179557A/ja active Pending
-
2002
- 2002-12-09 US US10/314,336 patent/US7618394B2/en not_active Expired - Fee Related
-
2006
- 2006-07-12 JP JP2006192130A patent/JP4430636B2/ja not_active Expired - Lifetime
- 2006-11-06 JP JP2006301005A patent/JP2007051160A/ja active Pending
-
2007
- 2007-08-31 US US11/848,432 patent/US7942846B2/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3788315A (en) * | 1971-04-20 | 1974-01-29 | S Laurens | Disposable cutaneous transjector |
WO1992004439A1 (en) * | 1990-08-30 | 1992-03-19 | Brian John Bellhouse | Ballistic apparatus |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101797411A (zh) * | 2010-03-18 | 2010-08-11 | 傅雅芬 | 一种气压式无针注射器动力头 |
CN101797411B (zh) * | 2010-03-18 | 2011-12-07 | 傅雅芬 | 一种气压式无针注射器动力头 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1109102C (zh) | 用超声气流输注粒子的无针注射器 | |
US6592545B1 (en) | Particle delivery | |
KR100777146B1 (ko) | 소형화된 무바늘 주사기 | |
USRE43824E1 (en) | Needleless syringe | |
US20040015126A1 (en) | Needle-less injector of miniature type | |
JP2007518499A (ja) | ジェット式注射器の衝撃チャンバ | |
AU765843B2 (en) | Needleless syringe | |
JP4658957B2 (ja) | ジェット式供給装置用衝撃チャンバ | |
JP2002538901A (ja) | 針なしシリンジ | |
US7060048B1 (en) | Needleless syringe | |
WO2002007803A1 (en) | Needleless syringe |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C17 | Cessation of patent right | ||
CX01 | Expiry of patent term |
Expiration termination date: 20140408 Granted publication date: 20030521 |