WO1998031414A1 - An insufflator assembly - Google Patents
An insufflator assembly Download PDFInfo
- Publication number
- WO1998031414A1 WO1998031414A1 PCT/SE1998/000037 SE9800037W WO9831414A1 WO 1998031414 A1 WO1998031414 A1 WO 1998031414A1 SE 9800037 W SE9800037 W SE 9800037W WO 9831414 A1 WO9831414 A1 WO 9831414A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tube
- insufflator
- powder
- dose
- elongate member
- Prior art date
Links
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
- A61M13/00—Insufflators for therapeutic or disinfectant purposes, i.e. devices for blowing a gas, powder or vapour into the body
-
- 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
- A61M2250/00—Specially adapted for animals
Definitions
- the present invention relates to an insufflator and an insufflator assembly incorporating the same.
- Insufflator assemblies are known for blowing or forcing doses of powder containing medicament into the lungs of animals.
- insufflator assemblies are used during pharmaceutical trials to deliver powder containing medicament into the lungs of small animals, such as mice.
- the dose of powder delivered to small animals is particularly small, typically in the range of from 20 to 25 ⁇ g. As such, it is difficult both to measure a dose of powder accurately and to provide a dose of powder in such a manner that the entire dose of powder is carried into the lungs of an animal.
- the lungs of small animals are comparatively small, such that only a small volume of air can be used to deliver a dose of powder.
- the tidal volume that is the volume of air passing into and out of the lungs in each breath, is only about 0.15 ml. As such, it is difficult to provide an air flow which will carry the entire dose of powder into the lungs of an animal without exceeding the capacity of the lungs of the animal.
- One known insufflator assembly comprises a sample chamber connected between a delivery tube and a syringe.
- the sample chamber which is of relatively large dimension, comprises two halves which are separated to load a dose of powder thereinto.
- a dose of powder is loaded into the sample chamber and the delivery tube is then inserted into an airway of an animal, usually the laryngeal tract.
- the plunger of the syringe is then pushed rapidly into the body thereof so as to drive a predetermined volume of air through the sample chamber and carry the dose of powder from the sample chamber through the delivery tube and into the lungs of the animal.
- the characteristics of the air flow are highly dependent upon how rapidly the user pushes the plunger of the syringe into the body thereof.
- the loading of powder into the sample chamber requires the user both to measure precisely a dose of powder and to ensure that the entire measured dose of powder is loaded into the sample chamber. Further, it is difficult to ensure that the entire dose of powder is delivered into the lungs of the animal.
- an insufflator assembly comprising: an insufflator comprising a delivery component for delivering powder into an airway of an animal, a metering component for providing a dose of powder to the delivery component and an inlet for receiving a stream of gas; and means for providing a stream of gas to the inlet of the insufflator so as to carry the dose of powder into the airway of the animal, the means comprising a chamber of a predetermined volume for containing gas at a predetermined pressure above atmospheric, a pressurized gas source for providing gas of a predetermined pressure to the chamber, a first valve for selectively connecting the chamber to the pressurized gas source and a second valve for selectively connecting the chamber to the inlet of the insufflator.
- the present invention also provides a method of providing a stream of gas containing powder, comprising the steps of: pressurizing a chamber of a predetermined volume with gas at a predetermined pressure above atmospheric; sealing the chamber; and connecting the chamber to an inlet of an insufflator loaded with a dose of powder so as to release the pressurized gas into the insufflator and entrain the dose of powder in a stream of gas.
- the present invention ensures that too great a volume of gas is not driven into the lungs of an animal.
- the present invention can be configured to use an optimum volume of gas.
- the insufflator assembly is triggered on the opening of only a single valve, the flow characteristics of the gas flow are substantially the same for each delivery. In particular, the flow characteristics are independent of the actions of a user.
- the flow characteristics are particularly suited to powder delivery, since, on opening the second valve, gas of high pressure and high velocity is immediately released.
- the initial high pressure and high velocity gas flow achieved by the present invention is particularly effective in deagglomerating a packed dose of powder.
- the volume of gas delivered is from 1 to 2 ml.
- valves may be mechanical, but when the valves are any of pneumatic, electrical or magnetic, the insufflator assembly is more readily controllable.
- the second valve should be a quick-opening valve.
- the second valve is connected to the insufflator by tubing of small bore and short length.
- tubing of small bore and short length.
- the present invention further provides an insufflator assembly, comprising: an insufflator for insertion into an airway of an animal and for delivering a dose of powder into the airway of the animal, the insufflator comprising a tube with two open ends; and a loading component comprising an elongate member having an end face for insertion into one end of the tube and for movement to a predetermined position proximate the other end of the tube so as to define a space between the other end of the tube and the end face of the elongate member, which space is in use filled with a dose of powder.
- the present invention still fiirther provides a method of loading a dose of powder into an insufflator comprising a tube with two open ends, comprising the steps of: inserting an elongate member of a loading component into one end of the tube, the elongate member having an end face; moving the end face of the elongate member through the tube to a predetermined position proximate the other end of the tube; and filling a space in the tube between the other end of the tube and the end face of the elongate member with a dose of powder.
- the dose of powder may be accurately selected with relative ease by varying the volume of the space defined in the tube.
- the volume of the space is set so as to provide a dose of powder of from 20 to 25 ⁇ g.
- the insufflator further comprises a further tube having two open ends, one end being for insertion into the airway of the animal and the other end being connectable with the other end of the first-mentioned tube.
- the present invention yet further provides an insufflator for delivering a dose of powder into an airway of an animal, comprising: a first tube having two open ends, one end being for insertion into an airway of an animal; and a second tube having two open ends, one end for receiving a stream of gas and the other end being in use loaded with a dose of powder and connected to the other end of the first tube.
- the present invention still yet further provides a method of providing a dose of powder in an insufflator for subsequent dispersion in a stream of gas, comprising the steps of: providing first and second connectable tubes; filling one end of one tube with a dose of powder; and connecting the one end of the one tube to one end of the other tube.
- a dose of powder is provided directly in the flow path through the insufflator.
- the dose of powder is located at the inlet of the first tube such that the dose of powder can be delivered effectively therethrough.
- the other end of the second tube is inserted into the other end of the first tube.
- the present invention contemplates for the first time that the airways with which the insufflator may be used include nasal passageways and that powder containing medicament may be delivered to the nasal cavities.
- the present invention extends to a method of delivering powder containing medicament to nasal cavities by inserting an insufflator into a nasal passageway.
- Medicaments suitable for administration by the present invention are any which may be delivered into airways and include for example ⁇ 2-adrenoreceptor agonists, for example, salbutamol, terbutaline, rimiterol, fenoterol, reproterol, adrenaline, pirbuterol, isoprenaline, orciprenaline, bitolterol, salmeterol, formoterol, clenbuterol, procaterol, broxaterol, picumeterol, TA-2005, mabuterol and the like, and their pharmacologically acceptable esters and salts; anticholinergic bronchodilators, for example, ipratropium bromide and the like; glucocorticosteroids, for example, beclomethasone, fluticasone, budesonide, tipredane, dexamethasone, betamethasone, fluocinolone, triamcinolone acetonide, mometasone and the
- Figure 1 illustrates the principal elements of an insufflator assembly in accordance with a first embodiment of the present invention
- Figure 2 illustrates the delivery component of the insufflator of the insufflator assembly of the first embodiment of the present invention
- Figure 3 illustrates the metering component of the insufflator of the insufflator assembly of the first embodiment of the present invention
- Figure 4 illustrates the metering component of the insufflator and the loading component when fitted together of the insufflator assembly of the first embodiment of the present invention
- Figure 5 illustrates the loading component of the insufflator assembly of the first embodiment of the present invention
- Figure 6 illustrates the insufflator of an insufflator assembly in accordance with a second embodiment of the present invention
- Figure 7 illustrates the delivery component of the insufflator of the insufflator assembly of the second embodiment of the present invention
- Figure 8 illustrates the metering component of the insufflator of the insufflator assembly of the second embodiment of the present invention
- Figure 9 illustrates the metering component of the insufflator and the loading component when fitted together of the insufflator assembly of the second embodiment of the present invention.
- Figure 10 illustrates the loading component of the insufflator assembly of the second embodiment of the present invention.
- the insufflator assembly comprises an insufflator comprising a delivery component 1 for delivering powder into the laryngeal tract of an animal and a metering component 3 for providing a dose of powder to the delivery component 1, a loading component 5 for use in loading a dose of powder into the metering component 3 of the insufflator and an air supply means comprising a firing unit 7 and a pressurized air source 9 connectable to the insufflator for providing an air flow to carry the dose of powder into the lungs of the animal.
- the delivery component 1 comprises a delivery tube 11 for insertion into the laryngeal tract of an animal, which delivery tube 11 is preferably a cannula similar to the needle of a syringe and may be metallic.
- One end of the delivery tube 11 is provided with a connector 13 having an inwardly tapered frusto-conical portion 15 for receiving the metering component 3.
- the other end of the delivery tube 11, which is inserted into the laryngeal tract, is preferably provided with a conically, olived or droplet shaped portion 17 so as to minimise trauma to the laryngeal tract during insertion.
- the connector 13 is a standard syringe connector, such as a Luer connector.
- the metering component 3 comprises a connector 19 having a frusto-conical portion 21 which is adapted to fit into and seal with the frusto-conical portion 15 of the connector 13 of the delivery component 1.
- the connector 19 further has an extension 23 in which is formed a peripheral groove 25.
- the metering component 3 further comprises a metering tube 27 which extends through the connector 19.
- One end of the metering tube 27, in this embodiment that end extending from the small end on the connector 19, is shaped and dimensioned to locate within at least an end part of the delivery tube 1 1 of the delivery component 1.
- the outer dimension of the metering tube 27 is substantially the same as the inner dimension of the delivery tube 11 such that the metering tube 27 and the delivery tube 11 are generally in sealing engagement when the metering component 3 is fitted to the delivery component 1 and the metering tube 27 is inserted into the delivery tube 11.
- a high pressure air flow is introduced directly into the delivery tube 11 and it is therefore unnecessary for the connection between the frusto-conical portions 15, 21 of the connectors 13, 19 to withstand such pressures.
- the connectors 13, 19 can be formed from other materials, such as plastics materials.
- the loading component 5, which is used to load a dose of powder into the metering component 3, comprises an elongate member 29 haying an end face 31 with an outer dimension substantially the same as the inner dimension of the metering tube 27 and a stop 33 adjustably mounted to one end of the elongate member 29.
- the stop 33 includes a through slot 35 in which the elongate member 29 is slidable, with the stop 33 being fixed in position relative to the elongate member 29 by screws 37 which are tightened against the elongate member 29.
- the length of the elongate member 29 protruding beyond the stop 33 is selected such that a space 39 of predetermined volume is defined by the inner surface of the metering tube 27 and the end face 31 of the elongate member 29 at the distal end of the metering tube 27.
- the loading component 5 further comprises a sprung component 41 which acts to retain the loading component 5 in a fixed position relative to the metering component 3 when fitted thereto.
- One end 43 of the sprung component 41 in this embodiment a U-shaped sprung member, is resiliently biased towards the elongate member 29.
- the end 43 of the sprung component 41 is located in the peripheral groove 25 in the extension 23 of the connector 19. In this way, the loading component 5 is securely retained relative to the metering component 3 during the step of filling the space 39 with a dose of powder.
- the end face 31 of the elongate member 29 should generally seal with the inner surface of the metering tube 27 at least in so far as is necessary to prevent any significant amount of powder passing beyond the end face 31.
- the end section of the inner surface of the metering tube 27 is of uniform cross-section. The length of this end section need only be as long as that of the required length of adjustment.
- the entire length of the inner surface of the metering tube 27 is of uniform cross-section and the elongate member 29 comprises a rod having an outer surface with a cross-section substantially the same as that of the inner surface of the metering tube 27.
- the end face 31 of the elongate member 29 can be provided with a seal, such as a cup seal.
- a seal such as a cup seal.
- the space 39 is filled with a predetermined dose of powder P.
- the space 39 is filled by dipping the distal end of the metering tube 27 into powder so as to pack the space 39 with a dose of powder P.
- the distal end of the metering tube 27 is dipped more than once, preferably 20 to 30 times and more preferably 40 or more times, to ensure good packing.
- the distal end of the metering tube 27 is actually pressed against a surface, preferably an elastic surface, such that powder is forced into the space 39.
- powder would be provided in a small cap-like container with a rubber-like base or insert.
- the metering component 3 may be fitted to the delivery component 1 before or after the loading component 5 is removed from the metering component 3. Owing to the nature of the very fine powder used, the dose of powder P will remain in a packed state within the metering tube 27 even if the loading component 5 is removed from the metering component 3 before fitting of the metering component 3 to the delivery component 1.
- the firing unit 7 comprises a chamber 45, in this embodiment provided by a tube, of predeterminable volume having an inlet to which is provided a first valve 47 and an outlet which is provided a second valve 49.
- the use of a tube enables small volumes to be accurately determined and also ensures an air flow with good flow characteristics.
- the chamber 45 may be of fixed volume or may incorporate means for varying the volume according to particular requirements.
- the valves 47, 49 are magnetic valves, but any other easily controlled valves could be used.
- the inlet of the chamber 45 is connected via the first valve 47 to the pressurized air source 9 with tubing 51.
- the outlet of the chamber 45 is connected via the second valve 49 to the metering tube 27 of the metering component 3 of the insufflator with flexible tubing 53.
- FIG. 6 illustrates the insufflator of an insufflator assembly in accordance with a second embodiment of the present invention.
- This insufflator is structurally quite similar to the insufflator of the above-described embodiment and in order not to unnecessarily duplicate description only the differences will be described. Operation of the insufflator is the same as that of the above-described embodiment.
- the end of the delivery tube 11 of the delivery component 1 into which the metering tube 27 of the metering component 3 is fitted is tapered and the metering tube 27 has an outer dimension which is greater than the inner dimension of the delivery tube 11. In this way, the metering tube 27 abuts the tapering section of the delivery tube 11 when the metering component 3 is fitted to the delivery component 1.
- the sprung component 41 of the loading component 5 comprises a spring and the metering component 3 includes a bent ring 55 instead of the extension 23.
- the loading component 5 can be securely retained in relation to the metering component 3 during the step of loading a dose of powder P into the space 39.
- the outer dimension of the metering tube 27 of the metering component 3 can be smaller than the inner dimension of the delivery tube 11 of the delivery component 1.
- a sealing fit of the delivery tube 11 and the metering tube 27 is not essential as the frusto-conical portions 15, 21 of the connectors 13, 19 can be configured to provide a hermetic seal, and thus any air introduced into the metering tube 27 can only pass through the delivery tube 11.
- the metering tube 27 may have generally the same or larger inner and outer dimensions than the delivery tube 11. In this embodiment, however, one or both of the end of the metering tube 27 and the end of the delivery tube 11 which are connected to one another are tapered such that the end of the metering tube 27 is located within the delivery tube 11.
- one or both of the delivery tube 11 and the metering tube 27 are tapered along either a portion or the entire length.
- the inner dimension of the metering tube 27 is no greater than the inner dimension of the delivery tube 11.
- the inner dimension of the metering tube 11 is no greater than the inner dimension of the delivery tube 11.
- the known insufflators in having sample chambers of a size sufficient to allow a user manually to load a dose of powder thereinto, suffer from the drawback that the air flow for carrying the powder is significantly reduced in pressure and velocity. Not only does this reduce the ability of the air flow to pick up the powder from the sample chamber, but also can mean that the smaller dimension delivery tube may provide such a back pressure that the air flow cannot carry the powder, particularly when agglomerated, into the delivery tube. This, in turn, can result in blocking of the opening to the delivery tube.
- the elongate member 29 in order to provide for adjustment of the length of the elongate member 29 extending from the stop 33, the elongate member 29 can be screwed into the stop 33, possibly with the use of a securing lock nut.
- the extension 23 of the connector 19 can be omitted and instead an olive can be fitted to the metering tube 27 to act as the part behind which the sprung component 41 of the loading component 5 engages.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98901154A EP0971762A1 (en) | 1997-01-16 | 1998-01-13 | An insufflator assembly |
US09/029,597 US6203519B1 (en) | 1997-01-16 | 1998-01-13 | Insufflator assembly |
AU56853/98A AU721960B2 (en) | 1997-01-16 | 1998-01-13 | An insufflator assembly |
CA002276616A CA2276616A1 (en) | 1997-01-16 | 1998-01-13 | An insufflator assembly |
JP53421598A JP2001512331A (en) | 1997-01-16 | 1998-01-13 | Drug injection device |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9700104-4 | 1997-01-16 | ||
SE9700104A SE9700104D0 (en) | 1997-01-16 | 1997-01-16 | insufflator |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998031414A1 true WO1998031414A1 (en) | 1998-07-23 |
Family
ID=20405428
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE1998/000037 WO1998031414A1 (en) | 1997-01-16 | 1998-01-13 | An insufflator assembly |
Country Status (7)
Country | Link |
---|---|
US (1) | US6203519B1 (en) |
EP (1) | EP0971762A1 (en) |
JP (1) | JP2001512331A (en) |
AU (1) | AU721960B2 (en) |
CA (1) | CA2276616A1 (en) |
SE (1) | SE9700104D0 (en) |
WO (1) | WO1998031414A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003070110A1 (en) * | 2002-02-20 | 2003-08-28 | New X-National Technology K.K. | Drug administration method |
WO2006041483A1 (en) | 2004-10-07 | 2006-04-20 | Lexion Medical, Llc | Method and apparatus for delivering an agent to the abdomen |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7744557B2 (en) * | 1998-05-19 | 2010-06-29 | Lexion Medical, Llc | Method and apparatus for delivering an agent to the abdomen |
US7731704B2 (en) * | 1998-05-19 | 2010-06-08 | Lexion Medical, Llc | Method and apparatus for delivering an agent to the abdomen |
US20050107767A1 (en) * | 1998-05-19 | 2005-05-19 | Ott Douglas E. | Method and apparatus for delivering an agent to the abdomen |
US7918816B2 (en) * | 1998-05-19 | 2011-04-05 | Lexion Medical, Llc | Method and apparatus for delivering an agent to the abdomen |
US9028437B2 (en) * | 1998-05-19 | 2015-05-12 | Lexion Medical, Llc | Method for delivering an agent to the abdomen |
EP1392382B1 (en) | 2001-05-10 | 2008-08-06 | Vectura Delivery Devices Limited | Inhaler |
GB2375308A (en) * | 2001-05-10 | 2002-11-13 | Cambridge Consultants | Inhalers |
WO2004039415A2 (en) * | 2002-10-28 | 2004-05-13 | Northgate Technologies Inc. | Dual-capacity insufflator tube |
US7654975B2 (en) * | 2003-04-24 | 2010-02-02 | Northgate Technologies, Inc. | Mixed-gas insufflation system |
JP4928266B2 (en) * | 2003-10-07 | 2012-05-09 | ノースゲート テクノロジーズ インコーポレイテッド | System and method for delivering a substance to a body cavity |
WO2005042079A1 (en) * | 2003-10-31 | 2005-05-12 | Trudell Medical International | System and method for manipulating a catheter for delivering a substance to a body cavity |
WO2008015566A2 (en) * | 2006-08-04 | 2008-02-07 | Northgate, Technologies, Inc. | In-dwelling port for access into a body |
US8974771B2 (en) * | 2010-03-09 | 2015-03-10 | Penn-Century, Inc. | Apparatus and method for aerosol delivery to the lungs or other locations of the body |
US8926587B2 (en) | 2013-02-18 | 2015-01-06 | King Abdullah International Medical Research Center | Pneumatic device for treating intussusception |
US9572595B1 (en) | 2014-03-05 | 2017-02-21 | Northgate Technologies Inc. | In-dwelling port for access into a body |
WO2016022973A1 (en) * | 2014-08-07 | 2016-02-11 | Endoinsight, Inc. | Insufflation apparatus and method of use |
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US2722935A (en) | 1949-03-22 | 1955-11-08 | Robert E Thompson | Powder dispenser |
US5273531A (en) | 1992-09-21 | 1993-12-28 | Knoepfler Dennis J | Method of applying thrombic powder in laparoscopic procedures |
US5542412A (en) | 1995-03-08 | 1996-08-06 | Century; Theodore J. | Powder Dispenser |
Family Cites Families (9)
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US4464169A (en) * | 1981-10-15 | 1984-08-07 | Kurt Semm | Apparatus and method for insufflating fluid media into a cavity |
US4878894A (en) * | 1987-02-26 | 1989-11-07 | Sutter Leroy V | Gas/saline valve with suction control |
US5061239A (en) * | 1990-01-31 | 1991-10-29 | Shiels William E | Intussusception air reduction system |
JPH07508443A (en) * | 1992-07-07 | 1995-09-21 | 544456 ビー シー リミテッド | Venting methods and devices |
US5246419A (en) * | 1992-09-04 | 1993-09-21 | Omnivision, Inc. | Intra-abdominal insufflation apparatus |
TW259716B (en) * | 1992-10-09 | 1995-10-11 | Birtcher Med Syst | |
US5399159A (en) * | 1993-03-30 | 1995-03-21 | Origin Medsystems, Inc. | Apparatus and method for hand-held insufflation |
US5800381A (en) * | 1994-02-25 | 1998-09-01 | Ognier; Jean-François | Medical gas insufflator with automatic gas flow control |
US5514087A (en) * | 1994-08-26 | 1996-05-07 | Karl Storz Gmbh & Co. | Self-regulating insufflator |
-
1997
- 1997-01-16 SE SE9700104A patent/SE9700104D0/en unknown
-
1998
- 1998-01-13 AU AU56853/98A patent/AU721960B2/en not_active Ceased
- 1998-01-13 US US09/029,597 patent/US6203519B1/en not_active Expired - Fee Related
- 1998-01-13 JP JP53421598A patent/JP2001512331A/en active Pending
- 1998-01-13 CA CA002276616A patent/CA2276616A1/en not_active Abandoned
- 1998-01-13 WO PCT/SE1998/000037 patent/WO1998031414A1/en not_active Application Discontinuation
- 1998-01-13 EP EP98901154A patent/EP0971762A1/en not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2722935A (en) | 1949-03-22 | 1955-11-08 | Robert E Thompson | Powder dispenser |
US5273531A (en) | 1992-09-21 | 1993-12-28 | Knoepfler Dennis J | Method of applying thrombic powder in laparoscopic procedures |
US5542412A (en) | 1995-03-08 | 1996-08-06 | Century; Theodore J. | Powder Dispenser |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003070110A1 (en) * | 2002-02-20 | 2003-08-28 | New X-National Technology K.K. | Drug administration method |
US7427607B2 (en) | 2002-02-20 | 2008-09-23 | Next21 K.K. | Drug administration method |
WO2006041483A1 (en) | 2004-10-07 | 2006-04-20 | Lexion Medical, Llc | Method and apparatus for delivering an agent to the abdomen |
EP2457611A3 (en) * | 2004-10-07 | 2012-12-19 | Lexion Medical, LLC | Method and apparatus for delivering an agent to the abdomen |
Also Published As
Publication number | Publication date |
---|---|
US6203519B1 (en) | 2001-03-20 |
AU5685398A (en) | 1998-08-07 |
AU721960B2 (en) | 2000-07-20 |
SE9700104D0 (en) | 1997-01-16 |
CA2276616A1 (en) | 1998-07-23 |
JP2001512331A (en) | 2001-08-21 |
EP0971762A1 (en) | 2000-01-19 |
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