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51. 发明公开

EP0996470A1 METHOD FOR ENHANCING THE ECHOGENICITY AND DECREASING THE ATTENUATION OF MICROENCAPSULATED GASES 失效
标题翻译：为加强超声回波和方法来减小微囊化气体放缓
公开(公告)号：EP0996470A1
公开(公告)日：2000-05-03
申请号：EP98932957.8
申请日：1998-06-30
申请人： Acusphere, Inc.
发明人： CHURCH, Charles, C. , BERNSTEIN, Howard , STRAUB, Julie, Ann , BRUSH, Henry, T.
IPC分类号： A61K49/00 , A61B8/00
CPC分类号： A61B8/481 , A61K49/223
摘要： It has been discovered that microparticles formed from natural or synthetic polymer with thicker walls have significantly enhanced echogenicity as compared with microparticles having thinner walls. The effect of wall thickness has been determined experimentally as well as inserted into a formula for use in predicting the optimum conditions. In the preferred embodiment, the polymers are synthetic biodegradable polymers and the wall thickness is between about 100 and 660 nm, although wall thicknesses from about 20 nm to in excess to 500 nm can be used. The microparticles are manufactured with a diameter suitable for the targeted tissue to be imaged, for example, with a diameter for between 0.5 and 8 microns for intravascular administration, and a diameter of between 0.5 and 5 mm for oral administration for imaging of the gastrointestinal tract or other lumens. Preferred polymers are polyhydroxy acids such as polylactic acid-co-glycolic acid, polylactide or polyglycolide, most preferably conjugated to polyethylene glycol or other materials inhibiting uptake by the reticuloendothelial system (RES). The microspheres may be used in a variety of ultrasound imaging applications including cardiology applications, blood perfusion applications as well as for organ and peripheral vein imaging.

52. 发明公开

EP0957942A2 POLYMER-LIPID MICROENCAPSULATED GASES FOR USE AS IMAGING AGENTS 失效
标题翻译：聚合物脂质微囊气体及其照片中产生资金的应用
公开(公告)号：EP0957942A2
公开(公告)日：1999-11-24
申请号：EP97929669.0
申请日：1997-02-27
申请人： Acusphere, Inc.
发明人： BERNSTEIN, Howard , STRAUB, Julie, Ann , BRUSH, Henry, T. , CHURCH, Charles, C.
IPC分类号： A61K49 , C08J3
CPC分类号： A61K49/0002 , A61K49/0004 , A61K49/223
摘要： It has been discovered that the incorporation of gases, especially fluorinated gases such as perfluorocarbons, into microparticles formed from the combination of a natural or synthetic polymer and lipid have significantly enhanced echogenicity as compared with microparticles not including the lipid. Compounds other than lipids which are hydrophobic and limit the penetration and/or uptake of water into the microparticles can also be incorporated into the microparticles to enhance echogenicity. In the preferred embodiment, the polymers are synthetic biodegradable polymers. The microparticles are manufactured with a diameter suitable for the targeted tissue to be imaged, for example, with a diameter of between 0.5 and 8 microns for intravascular administration, and a diameter of between 0.5 and 5 mm for oral administration for imaging of the gastrointestinal tract or other lumens. Preferred polymers are polyhydroxy acids such as polylactic acid-co-glycolic acid, most preferably conjugated to polyethylene glycol or other materials inhibiting uptake by the reticuloendothelial system (RES). The most preferred lipids are phospholipids, preferably dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), diarachidoylphosphatidylcholine (DAPC), dibehenoylphosphatidylcholine (DBPC), ditricosanoylphosphatidylcholine, dilignoceroylphatidylcholine (DLPC), incorporated at a ratio of between 0.01-30 (w lipid/w polymer), most preferably between 0.1-10 (w lipid/w polymer). Microparticles for imaging using other detectable agents can be similarly manufactured.

53. 发明专利

CY1110151T1 ΤΥΠΟΠΟΙΗΣΗ ΔΟΣΟΛΟΓΙΑΣ ΣΚΙΑΓΡΑΦΙΚΟΥ ΜΕΣΟΥ ΓΙΑ ΥΠΕΡΗΧΟΥΣ 未知
公开(公告)号：CY1110151T1
公开(公告)日：2015-01-14
申请号：CY101100577
申请日：2010-06-24
申请人： ACUSPHERE INC
发明人： WALOVITCH RICHARD , BERNSTEIN HOWARD , CHICKERING III DONALD E , STRAUB JULIE
IPC分类号： A61K49/22
摘要： Κλινικέςμελέτεςέχουνδιεξαχθείκαιτυποποιήσειςειδικήςδοσολογίαςέχουναναπτυχθείχρησιμοποιώνταςπολυμερικάμικροσωματίδιαπουέχουνενσωματωμένασεαυτάαέριαυπερφθοράνθρακαταοποίαπαρέχουνσημαντικάενισχυμένεςεικόνεςμακράςδιάρκειας. Ητυποποίησηδοσολογίαςπεριλαμβάνειμικροσωματίδιαπουσχηματίζονταιαπόέναβιοσυμβατόπολυμερές, τοοποίοκατάπροτίμησηπεριλαμβάνειέναλιπίδιοενσωματωμένοσεαυτό, καιτοοποίοπεριέχειένανυπερφθοράνθρακαο οποίοςείναιαέριοστηνθερμοκρασίατουσώματος. Ταμικροσωματίδιαπαρέχονταισεένανασθενήσεμιαποσότητααποτελεσματικήώστεναενισχυθείη απεικόνισηυπερήχωνστουςκοιλιακούςθαλάμουςγιαπερισσότεροαπό 5 λεπτάή στομυοκάρδιογιαπερισσότεροαπόέναλεπτό, σεμιαδόσηπουκυμαίνεταιαπό 0.025 έως 8.0 χλστγρ. μικροσωματιδίων/Χλγρ. σωματικούβάρους. Κατάπροτίμησηη δόσηκυμαίνεταιαπό 0.05 έως 4.0 χλστγρ. μικροσωματιδίων/Χλγρ. σωματικούβάρους. Ητυποποίησηδοσολογίαςτυπικώςπαρέχεταισεέναφιαλίδιο. Μιατυπικήτυποποίησηείναιστηνμορφήξηρήςσκόνηςη οποίααναδημιουργείταιμεστείρονερόπριναπότηνχρήσημεπροσθήκητουύδατοςστοφιαλίδιοή στηνσύριγγατηςξηρήςσκόνηςκαιανακίνησηώστεναδώσειέναισοσμωτικόή ισότονοεναιώρημαμικροσωματιδίων.

54. 发明专利

CA2569134C ULTRASOUND CONTRAST AGENT DOSAGE FORMULATION 未知
公开(公告)号：CA2569134C
公开(公告)日：2010-11-23
申请号：CA2569134
申请日：2004-06-04
申请人： ACUSPHERE INC
发明人： WALOVITCH RICHARD , BERNSTEIN HOWARD , CHICKERING DONALD E III , STRAUB JULIE
IPC分类号： A61K49/22
摘要： Clinical studies have been conducted and specific dosage formulations developed using polymeric microparticles having incorporated therein perfluorocarbon gases that provide significantly enhanced images of long duration. The dosage formulation includes microparticles formed of a biocompatible polymer, preferably including a lipid incorporated therein, and containing a perfluorocarbon that is a gas at body temperature. The microparticles are provided to a patient in an amount effective to enhance ultrasound imaging in the ventricular chambers for more than 5 minutes or in the mycocardium for more than a minute, in a dose ranging from 0.025 to 8.0 mg microparticles/kg body weight. Preferably the dose ranges from 0.05 to 4.0 mg microparticles/kg body weight. The dosage formulation typically is provided in a vial. A typical formulation is in the form of a dry powder that is reconstituted with sterile water prior to use by adding the water to the vial or syringe of the dry powder and shaking to yield an isosmotic or isotonic suspension of microparticles.

55. 发明专利

DE602004026164D1 未知
公开(公告)号：DE602004026164D1
公开(公告)日：2010-05-06
申请号：DE602004026164
申请日：2004-06-15
申请人： ACUSPHERE INC
发明人： WALOVITCH RICHARD , BERNSTEIN HOWARD , CHICKERING DONALD E III , STRAUB JULIE
IPC分类号： A61K49/22

56. 发明专利

DK1973527T3 Fremgangsmåder til fremstilling af partikelbaserede farmaceutiske formulationer til parenteral indgivelse 未知
公开(公告)号：DK1973527T3
公开(公告)日：2010-02-01
申请号：DK06840263
申请日：2006-12-14
申请人： ACUSPHERE INC
发明人： ALTREUTER DAVID , BERNSTEIN HOWARD , BRITO LUIS , BRITO SHAINA , CARNEIRO OLINDA C , CHICKERING DONALD E , HUANG ERIC K , JAIN RAJEEV , NARASIMHAN SRIDHAR , PANDIT NAMRATA , STRAUB JULIE A
IPC分类号： A61K9/14

57. 发明专利

DE602006009710D1 未知
公开(公告)号：DE602006009710D1
公开(公告)日：2009-11-19
申请号：DE602006009710
申请日：2006-12-14
申请人： ACUSPHERE INC
发明人： ALTREUTER DAVID , BERNSTEIN HOWARD , BRITO LUIS , BRITO SHAINA , CARNEIRO OLINDA C , CHICKERING DONALD E , HUANG ERIC K , JAIN RAJEEV , NARASIMHAN SRIDHAR , PANDIT NAMRATA , STRAUB JULIE A
IPC分类号： A61K9/14
摘要： A method is provided for making a parenteral dosage form of a pharmaceutical agent which includes (a) providing particles of a pharmaceutical agent; (b) blending the particles with particles of at least one bulking agent to form a first powder blend, which does not include a surfactant; (c) milling the first powder blend to form a milled blend which comprises microparticles or nanoparticles of the pharmaceutical agent; and (d) reconstituting the milled blend with a liquid vehicle, which includes at least one surfactant, for parenteral administration. A method also is provided which includes (a) providing particles of a pharmaceutical agent; (b) blending these particles with particles of an excipient to form a first blend; and (c) milling the first blend to form a milled blend that includes microparticles or nanoparticles, which exhibits a greater dispersibility, wettability, and suspendability as compared to the particles of step (a) or the first blend.

58. 发明专利

ES2216889T5 APARATO DE SECADO POR PULVERIZACION Y SUS PROCEDIMIENTOS DE UTILIZACION. 未知
公开(公告)号：ES2216889T5
公开(公告)日：2009-03-01
申请号：ES00928391
申请日：2000-04-26
申请人： ACUSPHERE INC
发明人： CHICKERING DONALD E , KEEGAN MARK J , RANDALL GREG , BERNSTEIN HOWARD , STRAUB JULIE
IPC分类号： B01J2/04 , F26B3/06 , A61K9/16 , B01D1/18 , F26B17/10 , F26B17/16 , F26B23/10
摘要： Un aparato de secado por pulverización que comprende: una cámara de secado primaria que tiene un espacio de flujo interno que termina en una salida de descarga, y una cámara de secado secundaria que comprende una tubería que tiene una entrada en comunicación fluida con la salida de descarga de la cámara de secado, donde la relación del área de sección transversal de la cámara de secado primaria con respecto al área de sección transversal de la tubería es al menos 4:3, y donde la relación de la longitud de la tubería con respecto a la longitud de la cámara de secado primaria es al menos 2:1.

59. 发明专利

PT996470E MÉTODO PARA AUMENTAR A ECOGENICIDADE E DIMINUIR A ATENUAÇÃO DE GASES MICROENCAPSULADOS 未知
公开(公告)号：PT996470E
公开(公告)日：2007-03-30
申请号：PT98932957
申请日：1998-06-30
申请人： ACUSPHERE INC
发明人： BERNSTEIN HOWARD , STRAUB JULIE ANN , CHURCH CHARLES C , BRUSH HENRY T
IPC分类号： A61K49/00 , A61K49/22 , A61B8/00

60. 发明专利

IL139252A MATRICES FORMED OF POLYMER AND HYDROPHOBIC COMPOUNDS FOR USE IN DRUG DELIVERY 未知
公开(公告)号：IL139252A
公开(公告)日：2006-10-31
申请号：IL13925200
申请日：2000-10-24
申请人： ACUSPHERE INC
IPC分类号： A61K9/16 , A61K9/22 , A61K9/52 , A61K47/24 , A61K47/30
摘要： A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as "hydrophobic compounds") is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug.

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