|Publication number||US3894538 A|
|Publication date||Jul 15, 1975|
|Filing date||Aug 6, 1973|
|Priority date||Aug 10, 1972|
|Also published as||DE2239432A1, DE2239432B2|
|Publication number||US 3894538 A, US 3894538A, US-A-3894538, US3894538 A, US3894538A|
|Original Assignee||Siemens Ag|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (11), Referenced by (168), Classifications (11)|
|External Links: USPTO, USPTO Assignment, Espacenet|
United States Patent 1191 Richter 1 July 15, 1975 DEVICE FOR SUPPLYING MEDICINES  Inventor: Gerhard Richter, Erlangen, Germany  Filed: Aug. 6, 1973 [211 App]. No.: 386,058
 Foreign Application Priority Data Aug. 10, 1972 Germany 2239432  US. Cl. 128/260; 204/301; 128/214 F; 128/272; l28/2.1 E; l28/2.1 R; 128/218 R; 222/95  Int. Cl A61m 31/00  Field of Search l28/171.1, 127-131, 128/260, 272, 2.1 E, 2 R, 213, 2.1 R, 218 R,
3,518,179 6/1970 Bleak et a1. 204/195 P 3,604,417 9/1971 Stolzenberg 128/213 3,659,600 5/1972 Merrill 128/260 3,732,865 5/1973 Higuchi et al. 128/260 3,760,804 9/1973 Higuchi et al. 128/260 3,760,805 9/1973 Higuchi 128/260 3,760,984 9/1973 Theeuwes 222/95 Primary Examiner-Aldrich F. Medbery Attorney, Agent, or Firm-V. Alexander Scher  ABSTRACT A device for supplying medicines or the like to the body of man or beast has a container for preserving a medicine as well as means for changing the volume of the container. The container has an opening through which the medicine is ejected when the volume of the container is diminished. The invention is particularly characterized by the provision of another container operatively joined to the first-mentioned container and having a variable volume for varying the volume of the first-mentioned container. The change in volume of the other container is produced by gas or liquid particles diffused or entering through electrical fields or by electrolytical gas development within the container.
20 Claims, 3 Drawing Figures  References Cited UNITED STATES PATENTS 2,913,386 11/1959 Clark,.lr ..204/195P 3,023,750 3/1962 Baron 128/214F 3,050,665 8/1962 Hurd ..204/231 3,485,235 12/1969 Felson 128/2 V 1 f 13 9 16 3 4-6 10 15 I? 11 12 '1 DEVICE FOR SUPPLYING MEDICINES This invention relates to a device for supplying medicines or the like to the body of man or beast. having a container for preserving a medicine as well as means for changing the volume of the container. The container has an opening through which the medicine is ejected when the volume of the container is diminished. The term medicine as used herein is intended to cover all substances which are used to improve. reinstate or maintain the health of a patient. such as for example. vitamins or hormones.
During many illnesses the patients must be provided with medicines for lengthy time periods. for example. insulin for diabetes. corticosteroides for rheumatic illnesses. cytostatics for cancer. blood pressure regulators or also sex hormones. Up to now the supply of these medicines to the body of the patient took place primarily either orally (by swallowing tablets) or by simple injection at certain time intervals. Thus this supply of medicines is a discontinuous one and is poorly adapted to the actual requirements of the patient. When the patient provides himself with the medicines. the correct dosage is not always provided. However. in case of many medicines a very precise dosage is most important. since an excess of the medicine or insufficient dosage can have detrimental effects. Thus. for example. an insufficient amount of insulin causes comadiabetics. while an excess produces a hypoglycaumic shock. A lack of precision in the dosing of insulin probably causes an inclination of diabetics to arteriosclerosis.
An object of the present invention is the provision of a device which is operable without the assistance of a doctor or the use of the patient for providing automatically for long time periods a comparatively precise dosage of a medicine.
Other objects will become apparent in the course of the following specification.
ln the accomplishment of the objectives of the present invention it was found desirable to operatively combine with the container of the described type another container of variable volume serving as means for varying the volume of the medicine-carrying container. The change in volume of the second container is produced by gas or liquid particles diffused or entering through electrical fields or by electrolytical gas development within the container.
The regulation of the delivery of medicine out of the medicine-carrying container by a change in volume of another container operatively connected with the medicine carrying container, makes it possible to provide with the simplest technical means an extremely precise dosage of the medicine being delivered for long time periods. since volume changes of a container as such can be continuously precisely produced in a simple manner and can be controlled. The changes in volume actuated by gas or liquid particles diffused or entering through electrical fields or by electrolytical gas development, is particularly advantageous since such flows have an extremely precise uniformity over long time periods, so that changes in volume of the container regulating the delivery of the medicine out of the medicine carrying container also have a high extent of continuity over long time periods. Furthermore. the dosage of the medicine can be made extremely fine, since the gas or liquid diffused or field currents or electrolytically produced gas currents causing the passage of medicine out of the medicine-carrying container can be kept extremely small by suitable shaping or measuring of the gas or liquid diffusion passage or of the electrolytic gas developer in the container.
in accordance with the present invention the medicine-carrying container can be made totally or partly of elastic material and means can be provided for transforming volume changes of the other container into a compressing force exerted upon the elastic material. The other container can press with at least a part of its walls directly upon the elastic material of the medicinecarrying container. For that purpose the medicinecarrying container is preferably placed within the main container or so arranged that at least the elastic part of the medicine-carrying container constitutes at the same time a part of the wall of the main container.
According to a preferred embodiment of the present invention the main container has a rigid casing the interior of which is divided by a separating wall into two chambers one of which has an outflow opening and is used to receive the medicine. while the second one has a diaphragm window through which gas or liquid particles can be diffused or entered by electrical field action or which can contain a gas producer for electrolytic gas separation. whereby the separating wall can be pushed into the first chamber due to an increase of gas or liquid in the second chamber. The diffusion or entry of gas or liquid particles into the second chamber preferably takes place either in the usual osmotic manner or in the electro-osmotic manner.
While the normal osmotic diffusion effect permits substantially only a dosage of the medicine to be used extending continuously over the entire duration of the treatment. the electro-osmotic effect as well as the electrolytic gas production in a further container permit a-medicine dosage which can be operated or regulated from the outside to a certain extent. by setting currents of different strengths between electrodes required for producing the electro-osmotic effect or for electrolytic gas separation. The operation or regulation of the. dosage can take place preferably by measure value-signals which are obtained from or in the body of the patient and constitute a measure for the size of the body to be affected by the medicine.
Thedevice of the present invention is paticularly suitable for implantation into the body of a patient. However, it can be obviously used outside of the body. for example. by being carried upon the surface of the body.
.-'The invention will appear more clearly from the following detailed description. when taken in connection with the accompanying drawing showing by way of example. only. preferred embodiments of the inventive idea.
ln the drawing:
FIG. 1 is a section through an implantable device of the present invention operating according to normal osmose.
FIG. 2 is a section through an implantable device of the present invention operating according to electroosmose.
FIG. 3 is a section through an implantable device of the present invention wherein changes in volume of the container actuating the medicine-carrying container are caused by gases produced electrolytically in the container.
The casings are indicated by the numeral 1 in the 3 not transmit liquid and is well adapted. to tissue, for example. epoxide resin. I l
The interior of the casing l is divided by a diaphragm 2 into two separate chambers 3- and 4, whereby .the chamber 3 is used for receiving a medicine. for example. insulin for treating diabetes. while chamber 4 serves for creating osmotic pressure as the result of which the diaphragm 2 is slowly pressed into the chamber 3 and thus by this extension presses the medicine located in the'chamber 3 through an outflow opening 5 provided in the container. The diaphragm 2 consists of a liquid-tight material. preferably a -plastic. and is elastic. It is also possible to additionally metallize the diaphragm 2 as well as the interior of the medicine containing chamber 3 to provide greater im'permeability against liquids and to prevent possible chemical reactions of the medicine with the material of the casing or diaphragm, v
The liquid medicine driven through the opening S'is transported through a thin tube 6 connected to the opening 5 to a suitable location in the body of the patient. for example. into the blood flow, and is there released. The free end of the tube 6 is preferably provided with a finely porous plug 7 which prevents return diffusion of the body liquid into the medicinecontaining chamber 3 or an uncontrolled outflow of the medicine out of the chamber 3. The plug can consist of porous teflon or a hydrophylic material. such as cellulose. or an ion exchanging material. The width of the pores of the plug material shouldbe less than lOOum. preferably between 1 and 20am.
In the embodiment illustrated in FIG. 1 the creation of osmotic pressure in the chamber 4 takes place in a normal osmotic manner. For that purposethe wall of the chamber 4 is provided with a diaphragm window 8 consisting of a semi-permeable material which can transmit water or steam. and also small loose molecules or ions. but not the substance located within the chamber4 and used to buildup osmotic pressure in the chamber. I
The window 8 can be either rigid or can be held by porous rigid supports. preventing it from moving outwardly when pressure is increased. The material of the diaphragm can be either a hydrophobic material. for example. porous or also nonporous teflon, polyethylene or silicon. or the diaphragm can consist of a hydrophilic material. for example, cellulose. cellulose derivatives or ion exchangers. lf porous teflon is used as the diaphragm material. then the width of its individual pores must be narrower than the width of the pores of the material of the plug located at the outlet of the medicine transmitting tube 6.
To make certain that there will be a uniform and fine outflow of the medicine out of the ,chamber 3, the steam pressure in the chamber 4 must be small relatively to steam pressure in the body liquid surrounding the casing 1. Furthermore. changes of steam pressure in the pressure chamber must remain small during the operational period, compared with the steam pressure difference relatively to body liquid. The dosage of the medicine is then determined by the extent of diffusion of water or steam in the chamber 4. The extent of transmission of the semipermeable window 8, its size and with low steam partial pressure for the interior of the chamber 4.
If av material. is selected for the diaphragm window which transmits, ions, then the interior of the chamber 4 should be filled with a polyelectrolite or a gel. The osmotic pressure is then produced due to a so-called Donnan weight balance.
In the construction shown in FIG. 2 osmotic pressure in the chamber 4 is produced by an electro-osmotic effect. For that purpose the wall of the casing of the chamber 4 is provided with a diaphragm window 9 which is electrically charged and transmits ions. The window 9 is fixed between two electrodes 10 and 11 which produce a current through the window. The electrodes must be so polarized that counter ions move inwardly through the window to the solid ions, namely in the direction toward the chamber 4. If, for example, the window has cation exchange properties, then the electrode 10 must be polarized negatively and the electrode 11 must be polarized positively. When the electrodes 10' and 11 lie directly upon both sides of the window 9, they must be also made porous and filled with an electrolite, so that the electro-osmotic transportation of water through them'can take place. Furthermore. the-electrode 11 should be screened by a diaphragm 12 transmitting ions and suitable for tissue to avoid its contact with bodily tissue. v
The electrodes 10, 11 can be supplied with outside vcurrent, for example. by a battery 13 through a potentiometer 14 which can be connectedby outlet contacts 15 and 16 with the current connecting contacts 17 and 18 of the electrodes 10 and ll. If the electrodes consist of an inert material. such as platinum, then care must be taken that the. feeding current should not exceed the amount of l mA/cm so that no gas development should take place (diffusion limit current).
However. the electrodes '10 and 11 can be advantageously so constructed that they themselves will supply the current. For that purpose an electrode consisting for example of zinc. cadmium, aluminum or glucose can be used as anode and as cathode can be a silver/silver chloride or an oxygen/carbon electrode. In case of a combination of a glucose electrode with an oxygen electrode, the glucose electrode which, for example, consists of platinum black or Raney-platinumruthenium, must be applied to the side facing the chamber 4 of the hydrophilic window constructed as anion exchanger (electrode 10). The oxygen electrode consists of porous charcoal and is located upon the outer side of the window 9 (electrode 11). Since the coal electrode-is selective and reacts only with oxygen, the glucose is diffused without hindrance through the coal electrode and the window 9 to the non-selective precious metal electrode and can be reacted there. When a resistance 19 is connected, preferably a potentiometer for setting different cell currents, a current will flow between the electrodes.
The use of device devide ofthe'present invention 7 having a glucose-oxygen-electrode combination is par- 7 current between the electrodes is also directly depenthickness are to be selected depending upon the Ldesired dosage. A hygroscopic salt, such as ,rnagnes'ium-. Zincor calcium chloride, is suggested as-a substance dent froin'theglucose content of the tissue liquid of the patientlfa more or less strong current corresponding to height of the blood glucose mirror is produced in 'a' tim e'un it through the window, and thus more or less 'wateris fdiffu se cl in thesame timeperiod into the chamher 4 and thus due to a more or less quick filling of this space 4 a correspondingly strong or less strong insulin is transmitted through the opening 5 and tube 6' to the blood of the patient. Thus a device of this type carries out already by itself a certain regulating function with respect to an increased insulin delivery at a higher glucose mirror and a correspondingly weaker insulin delivery at a correspondingly lower glucose mirror.
However, even when other types of medicine are used it is possible to operate or regulate a corresponding adaptation of medicine delivery to the momentary requirement of the patient. by providing means which continuously supervise the body section to be influenced by the medicine and produce corresponding measuring signals which can be then used for operating or regulating the electrode current, for example. by correspondingly actuating the potentiometer 14 or 19. In case of a regulation as intended value is then used a normal value of the body size and the medicine delivery is regulated on the basis of body size signal-actual value-intended value deviation (over the current).
The amount of medicine which should be transmitted from the medicine container 3 into the tissue or blood of a patient corresponds to the amount ofsolution (water and ions) which is transmitted through the diaphragm window 8 or 9 into the chamber 4. In. the embodiment of the invention illustrated in FIG. 2 this amount of solution and thus the delivered amount of medicine are determined directly by the strength of electro-osmotically actuating current. For example. per Faraday (96500 As) are transported by a cation exchange diaphragm at a current strength of l mA/cm 50 mol of solution (corresponding to 90 gr.). Thus the delivery of 1 ml medicine requires about 100 As. If this amount of medicine is to be delivered within 24 hours, an electrode feeding current of about 1.25 mA is required.
In the embodiment shown in FIG. 3, as distinguished from those of FIGS. 1 and 2, the deviation of the diaphragm 2 does not take place by osmotic pressure in chamber 4, but a gas is produced electrolytically in chamber 4, which with increased volume moves the diaphragm 2 correspondingly into the medicine space 3. The electrolytic gas producer consists simply of an inert electrode for gas separation, for example, a precious metal electrode (platinum), as well as a counter electrode 21 (silver/silver chloride or zinc electrode). Between the electrodes 20, 21 a fixed electrolite 22 is located. The current feeding of the electrodes takes place through the battery connections 23 and 24.
Contrary to the embodiments of FIGS. 1 and 2, the movable diaphragm 2 of FIG. 3 is not flat but is partially folded. However, this difference is only a variant of the diaphragm construction of FIGS. 1 and 2 and has no significance for the basic working principle of the device of the present invention.
As shown in FIGS. 1 and 2, two narrow conically outwardly extending bore holes 25, 26 are provided for filling medicine in the medicine containing chamber 3 and for emptying liquid or gas in the chamber 4, the holes being closed by spring valves 27 and 28.
For example, a precisely fitting also conical injection needle is introduced into this opening or 26, which then opens automatically the valve 27 or 28 and by means of which the medicine container chamber 3 can befilled again or gas or liquid can be removed from the I Since the outflow opening is to be made as a narrow capillary; only small amounts of medicine which are within permissible tolerance limits can flow out during the refilling procedure due to variations in pressure.
l. A device for supplying medicines to the body of man or beast. comprising means forming a first container of'variable volume for containing a medicine and having an opening for delivery of medicine. means connected with the first-mentioned means and forming a second container of variable volume to vary the volume of the first-mentioned container. and means supplying volume varying means to the second mentioned container said volume varying means for said second container having a diaphragm window for receiving said volume varying means having two electrodes of different potentials and located on opposite sides of saiddiaphragm window and being embedded between said electrodes to provide a current or voltage supply for producing electrical fields so that fluid particles are transmitted into said second container in an electroosmotic manner. r
2. A device in accordance with claim 1, wherein said volume varying means comprise means electrolytically developing gas in the second-mentionedcontainer.
3. A device in accordance with claim 2, wherein the first-mentioned and the second-mentioned means jointly constitute a rigid casing having a separating wall dividing the interior of said easing into the firstmentioned container and the second-mentioned container, said separating wall pressing into the firstmentioned container when the second-mentioned container receives an excess of said volume varying means.
4. A device in accordance with claim 1, wherein the diaphragm window of the second-mentioned container is semipermeable and consists of a substance selected from the class consisting of hydrophobic material, hydrophilic material, porous teflon, non-porous teflon, polyethylene, silicon. cellulose, cellulose derivatives and ion exchangers.
5. A device in accordance with claim 1, wherein said diaphragm window consists of electrically charged material transmitting water. steam and ions. said electrodes producing current of such polarity that water is transmitted into the second-mentioned casing in an electro-osmotic manner.
6. A device in accordance with claim 5, having means supplying a current to said electrodes and having a potentiometer varying-the extent of this current.
7. A device in accordance with claim 5, wherein said electrodes are current producing electrodes and consist of a combination of a metallic electrode as anode of zinc, cadmium or aluminum with a silver/silver chloride or oxygen/carbon electrode as cathode or a combination of a selective oxygen electrode and a glucose electrode.
8. A device in accordance with claim 2, wherein means electrolytically developing gas comprise a precious metal inert electrode and a counter electrode selected from the class consisting of a silver/silver chlo-' ride electrode and a zinc electrode.
9. A device in accordance with claim 8. comprising an electronic steering and regulating device for steering and regulating the current between said electrodes depending upon measured value signals received from the body. said signals producing a measure for the size of the body to be influenced by the medicine.
10. A device in accordance with claim 3. wherein said casing consists of a substance impermeable to liquid and having at least an outer surface adaptable to tissue for transplanting it into a body.
11. A device in accordance with claim 1. comprising a plug closing said opening and consisting of a finely porous material.
12. A device in accordance with claim 11, wherein the pores of said material range between 1 ,u. and p. and are less than l()() p" 13. A device for supplying medicines to the body of man or beast. comprising means forming a first container of variable volume for preserving a medicine and having an opening for delivery of medicine. means connectcd with the first-mentioned means and forming a second container of variable volume for varying the volume of the first container. and a device supplying volume varying means to the second container. said volume varying device comprising a diaphragm window for said second container. which consists of electrically charged material transmitting particles. such as of water. steam and ions. and further comprising at least two electrodes locatedon opposite sides of said diaphragm window, said diaphragm window being embedded between said electrodes. said electrodes comprising a current or voltage supply for producing current of such polarity between such electrodes. that particles. such as of water. are transmitted into the second container in an electro-osmotic manner.
g 14. A device in accordance with claim' 13, wherein the diaphragm window of the second container is semipermeable and consists of a substance selected from the class consisting of hydrophilic material, such as cellulose, cellulose derivatives and ion exchangers.
15. A device in accordance with claim 13, said cur rent or voltage supplying means comprising a device. such as a potentiometer. for varying the extent of current between electrodes.
I 16. A device in accordance with claim l3,'wherein said electrodes are current producing electrodes and consist of a combination of a metallic electrode as anode of zinc. cadmium or aluminum with a silver/silver chloride or oxygen/carbon electrode as cathode.
17. A device in accordance with claim 13, wherein said electrodes are current producing electrodes and consist of a combination of a selective oxygen electrode and a glucose electrode.
18. A device in accordance with claim 13, wherein said electrode current or voltage supply comprises an electronic control device for controlling current between said electrodes depending upon measured value signals received from the body, said signals producing a measure for a variable quantity or parameter inside the body to be influenced bythe medicine.-
19. A device in accordance with claim 18, wherein tween 1 pm and 20 um.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US2913386 *||Mar 21, 1956||Nov 17, 1959||Jr Leland C Clark||Electrochemical device for chemical analysis|
|US3023750 *||Mar 4, 1959||Mar 6, 1962||Howard C Baron||Self-generating pressure device for infusion administration systems|
|US3050665 *||Jul 13, 1955||Aug 21, 1962||Ray M Hurd||Electrolytic product cell|
|US3485235 *||Dec 4, 1967||Dec 23, 1969||Felson Ronald||Capsule for the study and treatment of the digestive tract|
|US3518179 *||Mar 11, 1968||Jun 30, 1970||Beckman Instruments Inc||Temperature compensated electrochemical cell|
|US3604417 *||Mar 31, 1970||Sep 14, 1971||American Cyanamid Co||Osmotic fluid reservoir for osmotically activated long-term continuous injector device|
|US3659600 *||Feb 24, 1970||May 2, 1972||Charles River Foundation The||Magnetically operated capsule for administering drugs|
|US3732865 *||Jan 13, 1971||May 15, 1973||Alza Corp||Osmotic dispenser|
|US3760804 *||Jan 13, 1971||Sep 25, 1973||Alza Corp||Improved osmotic dispenser employing magnesium sulphate and magnesium chloride|
|US3760805 *||Jan 13, 1971||Sep 25, 1973||Alza Corp||Osmotic dispenser with collapsible supply container|
|US3760984 *||Sep 29, 1971||Sep 25, 1973||Alza Corp||Osmotically powered agent dispensing device with filling means|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US4077405 *||Mar 22, 1976||Mar 7, 1978||Siemens Aktiengesellschaft||Apparatus for infusing liquids into human or animal bodies|
|US4146029 *||May 31, 1977||Mar 27, 1979||Ellinwood Jr Everett H||Self-powered implanted programmable medication system and method|
|US4159720 *||Nov 28, 1977||Jul 3, 1979||Burton Andrew F||Infusion of liquids into tissue|
|US4204538 *||Jun 7, 1978||May 27, 1980||Imed Corporation||Cassette for intravenous controller|
|US4205676 *||Mar 13, 1978||Jun 3, 1980||Deley C. Humphrey||Air pumping for medical uses|
|US4217894 *||May 4, 1978||Aug 19, 1980||Siemens Aktiengesellschaft||Apparatus for supplying medication to the human or animal body|
|US4265241 *||Feb 28, 1979||May 5, 1981||Andros Incorporated||Implantable infusion device|
|US4382753 *||Sep 10, 1980||May 10, 1983||Avi, Inc.||Nonpulsating IV pump and disposable pump chamber|
|US4391600 *||Sep 15, 1980||Jul 5, 1983||Avi, Inc.||Nonpulsating IV pump and disposable pump chamber|
|US4410322 *||Sep 10, 1980||Oct 18, 1983||Avi, Inc.||Nonpulsating TV pump and disposable pump chamber|
|US4559037 *||Jan 20, 1984||Dec 17, 1985||Siemens Aktiengesellschaft||Device for the pre-programmable infusion of liquids|
|US4573994 *||Dec 7, 1981||Mar 4, 1986||The Johns Hopkins University||Refillable medication infusion apparatus|
|US4596575 *||May 23, 1984||Jun 24, 1986||Omikron Scientific Ltd.||Liquid delivery system particularly useful as an implantable micropump for delivering insulin or other drugs|
|US4639244 *||Jul 12, 1985||Jan 27, 1987||Nabil I. Rizk||Implantable electrophoretic pump for ionic drugs and associated methods|
|US4655765 *||Jun 1, 1984||Apr 7, 1987||Parker Hannifin Corporation||Fitting with prestressed septum|
|US4687423 *||Jun 7, 1985||Aug 18, 1987||Ivac Corporation||Electrochemically-driven pulsatile drug dispenser|
|US4697622 *||Jun 13, 1986||Oct 6, 1987||Parker Hannifin Corporation||Passive filling device|
|US4820273 *||Mar 1, 1988||Apr 11, 1989||Eaton Corporation||Implantable medication infusion device and bolus generator therefor|
|US4857048 *||Mar 21, 1988||Aug 15, 1989||Hewlett-Packard Company||IV pump and disposable flow chamber with flow control|
|US4886514 *||Mar 2, 1989||Dec 12, 1989||Ivac Corporation||Electrochemically driven drug dispenser|
|US4902278 *||Feb 18, 1987||Feb 20, 1990||Ivac Corporation||Fluid delivery micropump|
|US4941873 *||Feb 5, 1986||Jul 17, 1990||Ultradent Products, Inc.||Controlled diffusion medicament applicator|
|US4997371 *||Jun 22, 1988||Mar 5, 1991||Honda Giken Kogyo Kabushiki Kaisha||Dental agent applicator|
|US5041107 *||Oct 6, 1989||Aug 20, 1991||Cardiac Pacemakers, Inc.||Electrically controllable, non-occluding, body implantable drug delivery system|
|US5090963 *||Oct 19, 1990||Feb 25, 1992||Product Development (Z.G.S.) Ltd.||Electrochemically driven metering medicament dispenser|
|US5242406 *||Dec 16, 1991||Sep 7, 1993||Sil Medics Ltd.||Liquid delivery device particularly useful for delivering drugs|
|US5246371 *||Sep 1, 1992||Sep 21, 1993||Ultradent Products, Inc.||Method and apparatus for delivery of highly filled, thixotropic sealant to teeth|
|US5269684 *||Aug 31, 1992||Dec 14, 1993||Ultradent Products, Inc.||Adjustable brush delivery tip with secondary flow path|
|US5397303 *||Aug 6, 1993||Mar 14, 1995||River Medical, Inc.||Liquid delivery device having a vial attachment or adapter incorporated therein|
|US5398851 *||Aug 6, 1993||Mar 21, 1995||River Medical, Inc.||Liquid delivery device|
|US5423454 *||Aug 19, 1992||Jun 13, 1995||Lippman, Deceased; Lawrence G.||Method of propellant gas generation|
|US5553741 *||Dec 23, 1994||Sep 10, 1996||River Medical, Inc.||Liquid delivery device|
|US5558255 *||Jun 5, 1995||Sep 24, 1996||River Medical, Inc.||Liquid delivery device|
|US5571261 *||Aug 5, 1994||Nov 5, 1996||River Medical, Inc||Liquid delivery device|
|US5578005 *||Sep 16, 1994||Nov 26, 1996||River Medical, Inc.||Apparatus and methods for multiple fluid infusion|
|US5584667 *||Jun 6, 1995||Dec 17, 1996||Davis; David L.||Method of providing uniform flow from an infusion device|
|US5707499 *||Oct 6, 1995||Jan 13, 1998||Ceramatec, Inc.||Storage-stable, fluid dispensing device using a hydrogen gas generator|
|US5766147 *||Jun 7, 1995||Jun 16, 1998||Winfield Medical||Vial adaptor for a liquid delivery device|
|US5785688 *||May 7, 1996||Jul 28, 1998||Ceramatec, Inc.||Fluid delivery apparatus and method|
|US5803712 *||Feb 14, 1995||Sep 8, 1998||Patient Solutions, Inc.||Method of measuring an occlusion in an infusion device with disposable elements|
|US5836935 *||Jan 28, 1997||Nov 17, 1998||Ashton; Paul||Implantable refillable controlled release device to deliver drugs directly to an internal portion of the body|
|US5855761 *||Jun 27, 1996||Jan 5, 1999||Ceramatec, Inc.||Gas amplifier|
|US5899381 *||Feb 21, 1997||May 4, 1999||Ceramatec, Inc.||Electrochemical device for delivery of volatile substances|
|US5925030 *||Aug 4, 1995||Jul 20, 1999||Elan Corporation, Plc||Orally administrable delivery device|
|US5938640 *||Jun 4, 1997||Aug 17, 1999||M&R Consulting Services||Two-part fluid dispenser|
|US5939032 *||Apr 24, 1997||Aug 17, 1999||Samsung Electronics Co., Ltd.||Apparatus and method for on-line decomposition of hydrogen peroxide solution in fabrication of semiconductor device|
|US5964261 *||May 28, 1997||Oct 12, 1999||Baxter International Inc.||Implantation assembly|
|US5997821 *||Aug 7, 1997||Dec 7, 1999||Ceramatec Corporation||Gas amplifier|
|US6042704 *||Jan 13, 1998||Mar 28, 2000||Ceramatec, Inc.||Storage-stable, fluid dispensing device using a hydrogen gas generator|
|US6060196 *||Jan 12, 1998||May 9, 2000||Ceramtec, Inc.||Storage-stable zinc anode based electrochemical cell|
|US6146109 *||Jun 29, 1998||Nov 14, 2000||Alaris Medical Systems, Inc.||Infusion device with disposable elements|
|US6146898 *||Sep 22, 1998||Nov 14, 2000||Samsung Electronics Co., Ltd.||Apparatus and method for on-line decomposition of hydrogen peroxide solution in fabrication of semiconductor device|
|US6312227||Mar 30, 1993||Nov 6, 2001||I-Flow Corp.||Infusion device with disposable elements|
|US6520936||Jun 8, 2000||Feb 18, 2003||Medtronic Minimed, Inc.||Method and apparatus for infusing liquids using a chemical reaction in an implanted infusion device|
|US6701724||Jun 6, 2002||Mar 9, 2004||Nanopore, Inc.||Sorption cooling devices|
|US6742992||Nov 7, 2002||Jun 1, 2004||I-Flow Corporation||Infusion device with disposable elements|
|US6787008||Apr 2, 2002||Sep 7, 2004||Microlin, L.C.||Hydrogen generating cell with cathode|
|US6793462 *||Jul 25, 2002||Sep 21, 2004||Motorola, Inc.||Fluidic pump|
|US6814852||Jul 15, 2002||Nov 9, 2004||Hewlett-Packard Development Company, L.P.||Generation of gas in a lab-on-a-chip environment|
|US6968711||Jun 6, 2002||Nov 29, 2005||Nanopore, Inc.||Temperature controlled shipping containers|
|US7008403||Jul 19, 2002||Mar 7, 2006||Cognitive Ventures Corporation||Infusion pump and method for use|
|US7341581||Jan 27, 2006||Mar 11, 2008||Phluid, Inc.||Infusion pump and method for use|
|US7364568||Oct 21, 2002||Apr 29, 2008||Massachusetts Institute Of Technology||Microneedle transdermal transport device|
|US7374556||Jan 31, 2006||May 20, 2008||Tandem Diabetes Care||Infusion pump and method for use|
|US7429258||Sep 9, 2002||Sep 30, 2008||Massachusetts Institute Of Technology||Microneedle transport device|
|US7458965||May 26, 2005||Dec 2, 2008||Microlin, Llc||Fluid delivery device having an electrochemical pump with an ion-exchange membrane and associated method|
|US7470267||May 1, 2002||Dec 30, 2008||Microlin, Llc||Fluid delivery device having an electrochemical pump with an anionic exchange membrane and associated method|
|US7481792||Sep 6, 2005||Jan 27, 2009||Valeritas, Inc.||Fluid delivery and measurement systems and methods|
|US7544508||Feb 24, 2003||Jun 9, 2009||Universite Joseph Fourier||Osmotic actuator and engine|
|US7645263||Oct 21, 2002||Jan 12, 2010||Massachusetts Institute Of Technology||Impedance sensor|
|US7651475||Jan 11, 2008||Jan 26, 2010||Massachusetts Institute Of Technology||Microneedle transport device|
|US7718047||Oct 18, 2005||May 18, 2010||The Regents Of The University Of Colorado||Electrochemical high pressure pump|
|US7803148||Jun 7, 2007||Sep 28, 2010||Neurosystec Corporation||Flow-induced delivery from a drug mass|
|US7896867||Jul 1, 2005||Mar 1, 2011||Microlin, Llc||Fluid delivery device having an electrochemical pump with an ion-exchange membrane and associated method|
|US8056582||Aug 8, 2008||Nov 15, 2011||Tandem Diabetes Care, Inc.||System of stepped flow rate regulation using compressible members|
|US8080000||Dec 20, 2011||Acclarent, Inc.||Methods and apparatus for treating disorders of the ear nose and throat|
|US8088101||Oct 26, 2007||Jan 3, 2012||Acclarent, Inc.||Devices, systems and methods for treating disorders of the ear, nose and throat|
|US8090433||Jan 3, 2012||Acclarent, Inc.||Methods and apparatus for treating disorders of the ear nose and throat|
|US8100933||May 8, 2008||Jan 24, 2012||Acclarent, Inc.||Method for treating obstructed paranasal frontal sinuses|
|US8114062||Oct 1, 2009||Feb 14, 2012||Acclarent, Inc.||Devices and methods for delivering therapeutic substances for the treatment of sinusitis and other disorders|
|US8114113||Oct 4, 2005||Feb 14, 2012||Acclarent, Inc.||Multi-conduit balloon catheter|
|US8118757||Apr 30, 2007||Feb 21, 2012||Acclarent, Inc.||Methods and devices for ostium measurement|
|US8123722||Oct 29, 2007||Feb 28, 2012||Acclarent, Inc.||Devices, systems and methods for treating disorders of the ear, nose and throat|
|US8142422||Mar 4, 2008||Mar 27, 2012||Acclarent, Inc.||Devices, systems and methods for diagnosing and treating sinusitis and other disorders of the ears, nose and/or throat|
|US8146400||Jul 31, 2007||Apr 3, 2012||Acclarent, Inc.||Endoscopic methods and devices for transnasal procedures|
|US8172828||May 8, 2012||Acclarent, Inc.||Apparatus and methods for dilating and modifying ostia of paranasal sinuses and other intranasal or paranasal structures|
|US8182432||Mar 10, 2008||May 22, 2012||Acclarent, Inc.||Corewire design and construction for medical devices|
|US8190389||May 17, 2006||May 29, 2012||Acclarent, Inc.||Adapter for attaching electromagnetic image guidance components to a medical device|
|US8231608 *||May 8, 2009||Jul 31, 2012||Minipumps, Llc||Drug-delivery pumps and methods of manufacture|
|US8231609 *||May 8, 2009||Jul 31, 2012||Minipumps, Llc||Drug-delivery pumps and methods of manufacture|
|US8246582||Apr 29, 2008||Aug 21, 2012||Massachusetts Institute Of Technology||Microneedle transdermal transport device|
|US8267905||May 1, 2006||Sep 18, 2012||Neurosystec Corporation||Apparatus and method for delivery of therapeutic and other types of agents|
|US8298176||Jul 19, 2010||Oct 30, 2012||Neurosystec Corporation||Flow-induced delivery from a drug mass|
|US8317816||Nov 27, 2012||Acclarent, Inc.||Balloon catheters and methods for treating paranasal sinuses|
|US8348930||Mar 11, 2010||Jan 8, 2013||Microlin, Llc||Fluid delivery device with a diffusion membrane and electrochemical pump|
|US8388642||Aug 29, 2008||Mar 5, 2013||Acclarent, Inc.||Implantable devices and methods for treating sinusitis and other disorders|
|US8408421||Oct 29, 2008||Apr 2, 2013||Tandem Diabetes Care, Inc.||Flow regulating stopcocks and related methods|
|US8414473||Sep 16, 2009||Apr 9, 2013||Acclarent, Inc.||Methods and apparatus for treating disorders of the ear nose and throat|
|US8425457||Dec 29, 2009||Apr 23, 2013||Acclarent, Inc.||Devices, systems and methods for diagnosing and treating sinusitus and other disorder of the ears, nose and/or throat|
|US8435290||Mar 24, 2010||May 7, 2013||Acclarent, Inc.||System and method for treatment of non-ventilating middle ear by providing a gas pathway through the nasopharynx|
|US8439687||Dec 29, 2006||May 14, 2013||Acclarent, Inc.||Apparatus and method for simulated insertion and positioning of guidewares and other interventional devices|
|US8448824||Feb 26, 2009||May 28, 2013||Tandem Diabetes Care, Inc.||Slideable flow metering devices and related methods|
|US8485199||May 8, 2007||Jul 16, 2013||Acclarent, Inc.||Methods and devices for protecting nasal turbinate during surgery|
|US8650937||Sep 18, 2009||Feb 18, 2014||Tandem Diabetes Care, Inc.||Solute concentration measurement device and related methods|
|US8702626||Dec 29, 2006||Apr 22, 2014||Acclarent, Inc.||Guidewires for performing image guided procedures|
|US8715169||Oct 30, 2007||May 6, 2014||Acclarent, Inc.||Devices, systems and methods useable for treating sinusitis|
|US8721591||Jan 23, 2012||May 13, 2014||Acclarent, Inc.||Apparatus and methods for dilating and modifying ostia of paranasal sinuses and other intranasal or paranasal structures|
|US8740929||Feb 6, 2002||Jun 3, 2014||Acclarent, Inc.||Spacing device for releasing active substances in the paranasal sinus|
|US8747389||Apr 24, 2007||Jun 10, 2014||Acclarent, Inc.||Systems for treating disorders of the ear, nose and throat|
|US8764709||Jun 30, 2010||Jul 1, 2014||Acclarent, Inc.||Devices, systems and methods for treating disorders of the ear, nose and throat|
|US8764726||Aug 18, 2009||Jul 1, 2014||Acclarent, Inc.||Devices, systems and methods useable for treating sinusitis|
|US8764729||Dec 22, 2008||Jul 1, 2014||Acclarent, Inc.||Frontal sinus spacer|
|US8764786||Oct 9, 2012||Jul 1, 2014||Acclarent, Inc.||Balloon catheters and methods for treating paranasal sinuses|
|US8777926||Mar 15, 2013||Jul 15, 2014||Acclarent, Inc.||Apparatus and methods for dilating and modifying ostia of paranasal sinuses and other intranasel or paranasal structures|
|US8828041||Mar 18, 2010||Sep 9, 2014||Acclarent, Inc.||Devices, systems and methods useable for treating sinusitis|
|US8852143||Apr 7, 2010||Oct 7, 2014||Acclarent, Inc.||Devices, systems and methods for treating disorders of the ear, nose and throat|
|US8858511||Dec 16, 2008||Oct 14, 2014||Valeritas, Inc.||Fluid delivery and measurement systems and methods|
|US8858586||Jan 18, 2007||Oct 14, 2014||Acclarent, Inc.||Methods for enlarging ostia of paranasal sinuses|
|US8859269||Feb 2, 2006||Oct 14, 2014||Universite Joseph Fourier||Chemical activation of an actuator or an osmotic motor|
|US8864787||Apr 9, 2008||Oct 21, 2014||Acclarent, Inc.||Ethmoidotomy system and implantable spacer devices having therapeutic substance delivery capability for treatment of paranasal sinusitis|
|US8870893||Apr 29, 2010||Oct 28, 2014||Acclarent, Inc.||Devices, systems and methods for diagnosing and treating sinusitis and other disorders of the ears, nose and/or throat|
|US8894614||Feb 16, 2006||Nov 25, 2014||Acclarent, Inc.||Devices, systems and methods useable for treating frontal sinusitis|
|US8905922||Mar 26, 2012||Dec 9, 2014||Acclarent, Inc.||Devices, systems and methods for diagnosing and treating sinusitis and other disorders of the ears, nose and/or throat|
|US8932276||May 16, 2007||Jan 13, 2015||Acclarent, Inc.||Shapeable guide catheters and related methods|
|US8945088||Apr 28, 2010||Feb 3, 2015||Acclarent, Inc.||Apparatus and methods for dilating and modifying ostia of paranasal sinuses and other intranasal or paranasal structures|
|US8951225||May 18, 2006||Feb 10, 2015||Acclarent, Inc.||Catheters with non-removable guide members useable for treatment of sinusitis|
|US8961398||Oct 31, 2007||Feb 24, 2015||Acclarent, Inc.||Methods and apparatus for treating disorders of the ear, nose and throat|
|US8961495||Oct 29, 2007||Feb 24, 2015||Acclarent, Inc.||Devices, systems and methods for treating disorders of the ear, nose and throat|
|US8968269||Jan 18, 2012||Mar 3, 2015||Acclarent, Inc.||Multi-conduit balloon catheter|
|US8979888||Jul 30, 2009||Mar 17, 2015||Acclarent, Inc.||Paranasal ostium finder devices and methods|
|US8992478||Jan 17, 2013||Mar 31, 2015||Valeritas, Inc.||Fluid delivery and measurement systems and methods|
|US9039657||Sep 3, 2009||May 26, 2015||Acclarent, Inc.||Implantable devices and methods for delivering drugs and other substances to treat sinusitis and other disorders|
|US9039680||Apr 21, 2008||May 26, 2015||Acclarent, Inc.||Implantable devices and methods for delivering drugs and other substances to treat sinusitis and other disorders|
|US9050440||Sep 22, 2006||Jun 9, 2015||Acclarent, Inc.||Multi-conduit balloon catheter|
|US9055965||Mar 22, 2010||Jun 16, 2015||Acclarent, Inc.||Devices, systems and methods useable for treating sinusitis|
|US9072626||May 6, 2013||Jul 7, 2015||Acclarent, Inc.||System and method for treatment of non-ventilating middle ear by providing a gas pathway through the nasopharynx|
|US9084876||Mar 15, 2013||Jul 21, 2015||Acclarent, Inc.||Implantable devices and methods for delivering drugs and other substances to treat sinusitis and other disorders|
|US9089258||Mar 15, 2007||Jul 28, 2015||Acclarent, Inc.||Endoscopic methods and devices for transnasal procedures|
|US9101384||Jan 16, 2009||Aug 11, 2015||Acclarent, Inc.||Devices, systems and methods for diagnosing and treating sinusitis and other disorders of the ears, Nose and/or throat|
|US9107574||Dec 8, 2011||Aug 18, 2015||Acclarent, Inc.||Endoscopic methods and devices for transnasal procedures|
|US9107995||Jun 7, 2013||Aug 18, 2015||Minipumps, Llc||Drug-delivery pumps and methods of manufacture|
|US20040230183 *||Feb 18, 2004||Nov 18, 2004||Wisam Breegi||Drug delivery device and syringe for filling the same|
|US20040231346 *||Mar 5, 2004||Nov 25, 2004||Smith Douglas M.||Sorption cooling devices|
|US20050013698 *||May 26, 2004||Jan 20, 2005||Davis David Lyle||Infusion device with disposable elements|
|US20050038415 *||Jul 12, 2004||Feb 17, 2005||Rohr William L.||Method and apparatus for the treatment of obesity|
|US20050158841 *||Feb 24, 2003||Jul 21, 2005||Philippe Cinquin||Osmotic actuator and engine|
|DE3247232A1 *||Dec 21, 1982||Jul 5, 1984||Univ Johns Hopkins||Infusionssystem zur medikamentoesen versorgung|
|DE3333977A1 *||Sep 20, 1983||Mar 22, 1984||Infusaid Corp||Infusionspumpe|
|DE3390255C2 *||Oct 5, 1983||Jun 25, 1992||The Johns Hopkins University, Laurel, Md., Us||Implanted medication infusion appts. with pulsatile pump|
|DE3390255C3 *||Oct 5, 1983||Aug 20, 1998||Univ Johns Hopkins||Infusions-Vorrichtung|
|EP0091621A1 *||Mar 31, 1983||Oct 19, 1983||Milliken Research Corporation||Low flow constant rate pump|
|EP0209677A1 *||May 27, 1986||Jan 28, 1987||Ivac Corporation||Electrochemically-driven pulsatile drug dispenser|
|EP0259013A1 *||Aug 4, 1987||Mar 9, 1988||Pharmetrix Corporation||Portable controlled release osmotic infusion device|
|EP1403400A1 *||Jul 4, 2003||Mar 31, 2004||Hewlett-Packard Development Company, L.P.||Generation of gas in a lab-on-a-chip environment|
|EP1778335A2 *||Jul 18, 2005||May 2, 2007||ExploraMed NC1, Inc.|
|EP2263738A2 *||Jul 18, 2005||Dec 22, 2010||Acclarent, Inc.||Implantable devices for delivering drugs and other substances to treat sinusitis and other disorders|
|EP2845621A3 *||Jul 18, 2005||Apr 8, 2015||Acclarent, Inc.||Implantable devices for delivering drugs and other substances to treat sinusitis and other disorders|
|WO1983002063A1 *||Dec 7, 1982||Jun 23, 1983||Univ Johns Hopkins||Refillable medication infusion apparatus|
|WO1986003418A1 *||Dec 6, 1985||Jun 19, 1986||Loi H Tran||Therapeutic agent delivery system and method|
|WO1996041159A1 *||Jun 7, 1996||Dec 19, 1996||Ceramatec Inc||Gas amplifier|
|WO1997013007A1||Sep 25, 1996||Apr 10, 1997||Ceramatec Inc||Storage-stable, fluid dispensing device using a hydrogen gas generator|
|WO1999006614A1||Jul 29, 1997||Feb 11, 1999||Ceramatec Inc||Storage stable electrolytic gas generator for fluid dispensing applications|
|WO2000074751A1 *||Jun 8, 2000||Dec 14, 2000||Medical Res Group Inc||Method and apparatus for infusing liquids using a chemical reaction in an implanted infusion device|
|WO2002099345A1 *||Jun 6, 2002||Dec 12, 2002||Nanopore Inc||Sorption cooling devices and temperature-controlled shipping containers incorporating sorption cooling devices|
|WO2003018089A1 *||Aug 7, 2002||Mar 6, 2003||He Xu Jiang||Liquid delivering device|
|WO2003072941A2 *||Feb 24, 2003||Sep 4, 2003||Cinquin Olivier||Osmotic actuator and engine|
|WO2006082345A1 *||Feb 2, 2006||Aug 10, 2006||Univ Joseph Fourier||Chemical activation of an actuator or an osmotic motor|
|WO2007125456A2 *||Apr 18, 2007||Nov 8, 2007||Koninkl Philips Electronics Nv||Micropump with at least one gas releasing material|
|U.S. Classification||604/891.1, 424/424, 204/627, 222/95|
|International Classification||A61M5/155, A61M5/142|
|Cooperative Classification||A61M2005/14204, A61M5/155, A61M5/14276|
|European Classification||A61M5/155, A61M5/142P10|