ABSTRACT
Abstract
A drug delivery system provides for controlled mixing of drugs, using flow controllers to guide drugs into single or multiple catheters, enabling a single lumen catheter to dispense multiple drugs, diluting a concentrated drug to provide varying drug concentration, using a buffer fluid to deliver precise amounts of drug or to separate drugs within a catheter, and using a patient's bodily fluid as a diluent or buffer fluid. A drug testing/filler apparatus may be used prior to system use to facilitate filling of multiple reservoirs and may also be used for refilling. The system can provide bolus or continuous delivery and enable the measured delivery of drug to selected distal locations at independent rates. New types of catheter systems, catheter hub assemblies, and uses therefore are also described. New methods for promotion of healthy pregnancy and treatment of a developing fetus are disclosed.
Description
This is a continuation of application Ser. No. 12/853,941 filed on 2010 Aug. 10 which is a divisional of U.S. application Ser. No. 10/893,414 filed on Jul. 19, 2004 which is now U.S. Pat. No. 7,811,279, which is a continuation of PCT application No. PCT/CA2004/001033, filed on Jul. 16, 2004, which claims the benefit of Provisional Application No. 60/488,133, filed on Jul. 16, 2003, and claims the benefit of Provisional Application No. 60/574,195, filed on May 25, 2004, and further claims the benefit of Provisional Application No. 60/587,870, filed on Jul. 15, 2004.
The present invention relates to medical devices, and more particularly to partially or completely implantable drug delivery systems which can deliver one or more stored substances.
BACKGROUND
Patients often require continuous or bolus administration of medications which can be delivered at regularly occurring times, times dictated by a treatment regimen, in response to a patient's request, or in response to a biological/physiological event. An increasing assortment of implantable drug delivery systems are being designed to treat patients who may use the drug delivery technology to dispense therapeutic agents to treat medical conditions such as diabetes, arthritis, cancer, movement disorders such as spasticity, heart conditions and irregularities, various neurological or psychiatric conditions, disorders of the digestive system, autoimmune disorders, and many other medical conditions and disorders as well. The medical drug delivery technology can be used for a wide variety of medical, veterinary, pharmaceutical and research purposes, can be totally or partially implantable or, if small enough, can be ingestible.
Implantable osmostic pumps have been known for some time (e.g., U.S. Pat. No. 4,588,394). The more recent generation of implantable drug delivery systems can deliver two or more substances (e.g., U.S. Pat. No. 3,449,983), at controlled rates of delivery (e.g., U.S. Pat. No. 5,240,713). U.S. application 60/284,771 (the '771 application) and provisional Ser. No. 10/099,060 (the '060 application) provide for a programmable implantable pump system with several reservoirs and a multiple lumen catheter. The '711 application provides for bolus drug delivery over a short period of time, for delivering multiple substances independently at programmed rates of delivery to one or more regions, and for drug delivery based upon physiological need. However, mixing of different drugs between reservoirs is not addressed.
The '711 patent application discloses a multiple lumen catheter for delivering multiple substances to a specific site by using concentrically embedded lumen. This technique causes the diameter of the outer lumen of the catheter to increase, requiring more material, and creating a catheter which may not bend easily, and which may be more difficult to use when treating certain disorders, such as those of the central nervous system, where a smaller diameter catheter may be advantageous. A further disadvantage is that the internal lumen can break and be undetected. Further, when the diameter of a multiple lumen catheter grows beyond a certain limit, the amount of substance which is chronically held in the outer lumen may become great, thus depleting the amount of that substance which is in the pump and ready for delivery, and also increasing the probability of unwanted leakage. Further, having several multi-lumen catheters necessitates a considerable amount of substance, compared to a small diameter catheter.
U.S. provisional application Ser. No. 10/251,941 discloses a drug delivery system which contains a series of chambers which may each hold a different drug, each of which can be sent to different catheters. The '941 also contains an accumulator chamber between the reservoirs and the catheter, which is provided to hold drug overflow. While drugs may be mixed in the '941 application, this occurs by breaching the drug chambers themselves so that 100% of the drugs in those chambers become mixed.
Mixing of drugs can be important in order to produce therapeutic effects. For example, in chemotherapy, some of the drugs should not be mixed until immediately prior to use. Some drugs may potentiate the effects of other drugs, such as Sufentanil and Clonidine as described in U.S. Pat. No. 6,471,688 (the '688 patent), incorporated by reference herein. The '688 patent feeds two drugs to the same catheter, and can be designed to keep them from mixing until they reach the intended delivery site by using a dual, rather than a single, lumen catheter. In this embodiment the timing of the mixing is related to the rate of drug delivery. One disadvantage with this system is if a drug is to be delivered rapidly, but the desired mixing is to occur slowly or prior to delivery, the invention of the '688 patent would not achieve the desired drug mixing during the drug delivery.
U.S. Pat. No. 5,980,508 describes a system that allows for multiple drugs, multiple doses, and continuous or pulsatile/interval delivery. However, the technology is sub-optimal because the concentration and delivery system must be configured prior to the implantation of the pump, rather than being dynamically adjusted once implanted, based upon the needs of the patient.
U.S. Pat. No. 4,588,394 (the â394â patent) teaches a pump that has a separate single drug reservoir and a valve arrangement between the pump and the reservoir, however, the pump is between the catheter and the reservoir, and the intention of the invention is to provide an easily accessed refillable reservoir which can be located remotely from the pump, catheter, and the site of delivery. The '394 patent also describes, a two-step procedure which controls an arrangement of valves to realize filling and emptying the pumping chamber while decreasing the chance of the inadvertent introduction of the medication to the patient.
U.S. Pat App No 2002/0192751 A1 (the â751â application) teaches methods and devices for modulating the rate of delivery of a drug by simply diverting a drug away from a single delivery pathway using a remotely controllable flow regulator. The flow regulator only affects the amount of drug going to a single catheter. The diverted drug can be sent into the systemic circulation or captured in a waste reservoir. However, the waste reservoir is different from a method which utilizes the diverted drug since the drug in the waste reservoir is not used at a later time. Further, the flow regulator does not address the existence of the drug which is already in the catheter, which is an issue when using multiple drugs since this drug must be eliminated (e.g., dispensed or purged) before a subsequent drug can be delivered.
While some prior art (e.g., US 2002/0156462) teaches using multiple reservoirs and multiple catheters or multiple lumens, each reservoir is uniquely connected to a single lumen or catheter. Accordingly, this prior art does not teach more than one drug to be output from each respective lumen or catheters. Prior art U.S. Pat. No. 6,471,688 enables drugs from multiple reservoirs to be dispensed from a single catheter to a single target region within the body of the patient, but does not teach how to deliver drugs to multiple target regions simultaneously. Prior art U.S. Pat. No. 6,471,688 also teaches a system which can allow for a single fluid from a single reservoir to be dispensed at multiple locations at the distal end of the catheter.
Drug delivery systems containing sensors and multiple pumps have been described which allow the delivery of drug to occur in response to a physiological event. For example, U.S. Pat. No. 6,066,163, describes an adaptive neurostimulation system which contains a reservoir infusion apparatus which stimulates the central nervous system with drugs in response to abnormal states which are sensed by one or more sensors. U.S. Pat. No. 5,062,841 discloses an insulin pump which can be used to pump insulin directly into the bloodstream in response to blood glucose levels. U.S. Pat. No. 5,433,701 discloses an active ocular pressure control device which includes a pump which is selectively operated in response to a control signal from a pressure sensor. However, these patents relate primarily to algorithms and methods of using the sensed data to control the pumping/drug delivery system and dispense an appropriate drug.
The prior art US 2003/0171738 (the '738 application) suggests continuously drawing upon fluids available from the implantee, in response to the immediate drug delivery needs of the implantee, which is disadvantageously dependent upon the availability of the implantee's fluids concurrent to the time of delivery. Further, a chamber is provided in the drug delivery device of the '738 application (see FIG. 3A ), but this chamber only leads to a single catheter and the chamber has a fixed volume. Further, in FIG. 1 a of the '738 application a carrier fluid from the reservoir is mixed with various drugs located in the catheter and somehow transmitted in a distributed fashion to several catheters, but in this case the drugs are undesirably mixed deterministically by the path of the flow of fluids over the âwellsâ of a microchip which contain drugs. Much of the technology described in the '738 patent relies on a catheter which contains a microchip drug delivery device. This microchip cannot contain much drug and is difficult to refill, and instead of being refilled is sometimes simply replaced, thereby requiring possibly complicated surgical intervention. Further, since drugs are dispensed by opening âwellsâ, a specific amount of drug is suddenly made available to the carrier fluid which transmits the drug to the implantee. It is not clear what might occur with the remainder of the drug which is contained in the catheter after the necessary amount has been delivered to the subject. In other words, when the amount of drug which is necessary for a specific drug regimen is known prior to implantation, then an appropriate amount of drug can be put into the âwellsâ of the microchip device. However, in the case where drug is delivered based upon sensed data and the object is, for example, to maintain a sensed parameter within certain limits, the use of a microchip incorporated into a catheter, as is described by the '738 application has an inability to provide a drug concentration and amount which is optimal to effect a desired change.
It is an object of the present invention to provide a drug delivery system and method to obviate or mitigate at least some of the above presented disadvantages.
SUMMARY OF THE INVENTION
The drug delivery systems of the present invention can provide for mixing various drugs in an optimally controlled manner, use flow controllers to guide multiple drugs into a single or into multiple catheters, enable a single lumen catheter to treat a specific region with several drugs, allow for dilution of a concentrated drug in order to both increase the time between refilling and also to provide any concentration of a drug that might be desired, provide for using a buffer fluid to deliver exact amounts of several drugs from the same catheter or to separate several drugs within a single catheter, use external fluid present in the human body either as a diluent or buffer fluid, and provide for a drug testing/filler apparatus to be used prior to implant to ensure proper function and easy means of filling multiple reservoirs with different fluids, and also after implant for refilling operations. The drug delivery system (DDS) can perform both bolus and continuous delivery of substances, and enable the measured delivery of any one of several drugs to one or more distal locations at independently programmable rates. New methods for using the DDS in the promotion of healthy pregnancy and treatment of a developing fetus are also possible.
According to a first aspect there is provided an implantable drug delivery device for controlling a dispensing of a fluid drug to an internal target site of a patient, the device comprising: a first reservoir for storing a first fluid; an input port in fluid communication with the first reservoir; an output port in fluid communication with the first reservoir; a flow control system for controlling the transfer of the first fluid between the respective ports and the first reservoir, the flow control system having at least one flow controller; and a flow control module for directing the at least one flow controller to direct the flow of the first fluid between a selected one of the ports and the first reservoir.
According to a further aspect there is provided a catheter assembly for directing a selected fluid to at least one target site of a patient, the assembly comprising: a first lumen having a first proximal end for coupling to a drug delivery device and a first distal end for positioning at the target site; a second lumen having a second proximal end for coupling to the drug delivery device and a second distal end for positioning at the target site, the first lumen and the second lumen adapted for fluid communication therebetween; a flow control system positioned at the first and second distal ends for directing inter-lumen fluid flow between the first and second lumens and for directing output fluid flow from the distal ends to the target site, the flow control system having at least one directional flow controller adapted to receive at least one control signal from the drug delivery device.
According to a still further aspect there is provided a method of outputting by a catheter assembly a selected fluid to a target site of a patient, the catheter assembly having a first lumen and a second lumen adapted for fluid communication therebetween and a flow control system for directing inter-lumen fluid flow between the first and second lumens and for directing output fluid flow from the distal ends of the lumens to the target site, the method comprising the steps of: delivering into the catheter at least two fluids, one of which is a buffer fluid, such that an alternating sequence of the fluids resides in the lumens; configuring by the flow control system the fluid flow of the lumens for inter-lumen fluid flow and inhibiting fluid flow output from the lumens; operating a pump in fluid communication with the lumens to perform inter-lumen circulation on the fluid sequence within the lumens until a selected one of the fluids resides near the distal tip of the first lumen; configuring by the flow control system to inhibit the inter-lumen fluid flow and to enable output fluid flow from the distal end of the first lumen of the selected fluid; and pumping the selected fluid as the output fluid from the first lumen.
According to a still further aspect there is provided an apparatus for configuring a drug delivery device, the device including at least one fluid reservoir in fluid communication with a fluid output port and a fluid input port and at least one fluid flow controller for controlling fluid input and output with respect to the fluid reservoir, the apparatus comprising; a fluid input component for recording an amount value of input fluid directed to the input port of the device from a fluid source; a flow control component for coupling to the device to configure the fluid flow controller to direct the input fluid from the input port into the fluid reservoir; a sensor component for recording at least one operational state value of the device including a fill state value of the reservoir; and a processor component for accepting user input commands and for coordinating the operation of the input, control, and sensor components in response to the user input commands; wherein the recorded values are provided to the user of the apparatus.
Accordingly, it is a feature of the present invention to provide for a drug delivery system which is capable of controlled delivery of both bolus and continuous flow of one or more substances, which may be substantially mixed or which may be presented sequentially, and which are delivered through a single catheter or through multiple catheters.
It is another feature of the present invention to provide for a drug delivery system which is capable of delivering more than one concentration of a substance, and perform dose titration by modifying either the concentration, or rate of dispensing, or both.
It is another feature of the present invention to provide for a drug delivery system which draws upon and utilizes a biological fluid available from the patient, rather than, or in addition to, a synthetic fluid, as an active drug, a buffer fluid, or a diluent, and thereby decreases the need for filling the drug delivery system from a source outside the bod
This is a continuation of application Ser. No. 12/853,941 filed on 2010 Aug. 10 which is a divisional of U.S. application Ser. No. 10/893,414 filed on Jul. 19, 2004 which is now U.S. Pat. No. 7,811,279, which is a continuation of PCT application No. PCT/CA2004/001033, filed on Jul. 16, 2004, which claims the benefit of Provisional Application No. 60/488,133, filed on Jul. 16, 2003, and claims the benefit of Provisional Application No. 60/574,195, filed on May 25, 2004, and further claims the benefit of Provisional Application No. 60/587,870, filed on Jul. 15, 2004.
The present invention relates to medical devices, and more particularly to partially or completely implantable drug delivery systems which can deliver one or more stored substances.
BACKGROUND
Patients often require continuous or bolus administration of medications which can be delivered at regularly occurring times, times dictated by a treatment regimen, in response to a patient's request, or in response to a biological/physiological event. An increasing assortment of implantable drug delivery systems are being designed to treat patients who may use the drug delivery technology to dispense therapeutic agents to treat medical conditions such as diabetes, arthritis, cancer, movement disorders such as spasticity, heart conditions and irregularities, various neurological or psychiatric conditions, disorders of the digestive system, autoimmune disorders, and many other medical conditions and disorders as well. The medical drug delivery technology can be used for a wide variety of medical, veterinary, pharmaceutical and research purposes, can be totally or partially implantable or, if small enough, can be ingestible.
Implantable osmostic pumps have been known for some time (e.g., U.S. Pat. No. 4,588,394). The more recent generation of implantable drug delivery systems can deliver two or more substances (e.g., U.S. Pat. No. 3,449,983), at controlled rates of delivery (e.g., U.S. Pat. No. 5,240,713). U.S. application 60/284,771 (the '771 application) and provisional Ser. No. 10/099,060 (the '060 application) provide for a programmable implantable pump system with several reservoirs and a multiple lumen catheter. The '711 application provides for bolus drug delivery over a short period of time, for delivering multiple substances independently at programmed rates of delivery to one or more regions, and for drug delivery based upon physiological need. However, mixing of different drugs between reservoirs is not addressed.
The '711 patent application discloses a multiple lumen catheter for delivering multiple substances to a specific site by using concentrically embedded lumen. This technique causes the diameter of the outer lumen of the catheter to increase, requiring more material, and creating a catheter which may not bend easily, and which may be more difficult to use when treating certain disorders, such as those of the central nervous system, where a smaller diameter catheter may be advantageous. A further disadvantage is that the internal lumen can break and be undetected. Further, when the diameter of a multiple lumen catheter grows beyond a certain limit, the amount of substance which is chronically held in the outer lumen may become great, thus depleting the amount of that substance which is in the pump and ready for delivery, and also increasing the probability of unwanted leakage. Further, having several multi-lumen catheters necessitates a considerable amount of substance, compared to a small diameter catheter.
U.S. provisional application Ser. No. 10/251,941 discloses a drug delivery system which contains a series of chambers which may each hold a different drug, each of which can be sent to different catheters. The '941 also contains an accumulator chamber between the reservoirs and the catheter, which is provided to hold drug overflow. While drugs may be mixed in the '941 application, this occurs by breaching the drug chambers themselves so that 100% of the drugs in those chambers become mixed.
Mixing of drugs can be important in order to produce therapeutic effects. For example, in chemotherapy, some of the drugs should not be mixed until immediately prior to use. Some drugs may potentiate the effects of other drugs, such as Sufentanil and Clonidine as described in U.S. Pat. No. 6,471,688 (the '688 patent), incorporated by reference herein. The '688 patent feeds two drugs to the same catheter, and can be designed to keep them from mixing until they reach the intended delivery site by using a dual, rather than a single, lumen catheter. In this embodiment the timing of the mixing is related to the rate of drug delivery. One disadvantage with this system is if a drug is to be delivered rapidly, but the desired mixing is to occur slowly or prior to delivery, the invention of the '688 patent would not achieve the desired drug mixing during the drug delivery.
U.S. Pat. No. 5,980,508 describes a system that allows for multiple drugs, multiple doses, and continuous or pulsatile/interval delivery. However, the technology is sub-optimal because the concentration and delivery system must be configured prior to the implantation of the pump, rather than being dynamically adjusted once implanted, based upon the needs of the patient.
U.S. Pat. No. 4,588,394 (the â394â patent) teaches a pump that has a separate single drug reservoir and a valve arrangement between the pump and the reservoir, however, the pump is between the catheter and the reservoir, and the intention of the invention is to provide an easily accessed refillable reservoir which can be located remotely from the pump, catheter, and the site of delivery. The '394 patent also describes, a two-step procedure which controls an arrangement of valves to realize filling and emptying the pumping chamber while decreasing the chance of the inadvertent introduction of the medication to the patient.
U.S. Pat App No 2002/0192751 A1 (the â751â application) teaches methods and devices for modulating the rate of delivery of a drug by simply diverting a drug away from a single delivery pathway using a remotely controllable flow regulator. The flow regulator only affects the amount of drug going to a single catheter. The diverted drug can be sent into the systemic circulation or captured in a waste reservoir. However, the waste reservoir is different from a method which utilizes the diverted drug since the drug in the waste reservoir is not used at a later time. Further, the flow regulator does not address the existence of the drug which is already in the catheter, which is an issue when using multiple drugs since this drug must be eliminated (e.g., dispensed or purged) before a subsequent drug can be delivered.
While some prior art (e.g., US 2002/0156462) teaches using multiple reservoirs and multiple catheters or multiple lumens, each reservoir is uniquely connected to a single lumen or catheter. Accordingly, this prior art does not teach more than one drug to be output from each respective lumen or catheters. Prior art U.S. Pat. No. 6,471,688 enables drugs from multiple reservoirs to be dispensed from a single catheter to a single target region within the body of the patient, but does not teach how to deliver drugs to multiple target regions simultaneously. Prior art U.S. Pat. No. 6,471,688 also teaches a system which can allow for a single fluid from a single reservoir to be dispensed at multiple locations at the distal end of the catheter.
Drug delivery systems containing sensors and multiple pumps have been described which allow the delivery of drug to occur in response to a physiological event. For example, U.S. Pat. No. 6,066,163, describes an adaptive neurostimulation system which contains a reservoir infusion apparatus which stimulates the central nervous system with drugs in response to abnormal states which are sensed by one or more sensors. U.S. Pat. No. 5,062,841 discloses an insulin pump which can be used to pump insulin directly into the bloodstream in response to blood glucose levels. U.S. Pat. No. 5,433,701 discloses an active ocular pressure control device which includes a pump which is selectively operated in response to a control signal from a pressure sensor. However, these patents relate primarily to algorithms and methods of using the sensed data to control the pumping/drug delivery system and dispense an appropriate drug.
The prior art US 2003/0171738 (the '738 application) suggests continuously drawing upon fluids available from the implantee, in response to the immediate drug delivery needs of the implantee, which is disadvantageously dependent upon the availability of the implantee's fluids concurrent to the time of delivery. Further, a chamber is provided in the drug delivery device of the '738 application (see FIG. 3A ), but this chamber only leads to a single catheter and the chamber has a fixed volume. Further, in FIG. 1 a of the '738 application a carrier fluid from the reservoir is mixed with various drugs located in the catheter and somehow transmitted in a distributed fashion to several catheters, but in this case the drugs are undesirably mixed deterministically by the path of the flow of fluids over the âwellsâ of a microchip which contain drugs. Much of the technology described in the '738 patent relies on a catheter which contains a microchip drug delivery device. This microchip cannot contain much drug and is difficult to refill, and instead of being refilled is sometimes simply replaced, thereby requiring possibly complicated surgical intervention. Further, since drugs are dispensed by opening âwellsâ, a specific amount of drug is suddenly made available to the carrier fluid which transmits the drug to the implantee. It is not clear what might occur with the remainder of the drug which is contained in the catheter after the necessary amount has been delivered to the subject. In other words, when the amount of drug which is necessary for a specific drug regimen is known prior to implantation, then an appropriate amount of drug can be put into the âwellsâ of the microchip device. However, in the case where drug is delivered based upon sensed data and the object is, for example, to maintain a sensed parameter within certain limits, the use of a microchip incorporated into a catheter, as is described by the '738 application has an inability to provide a drug concentration and amount which is optimal to effect a desired change.
It is an object of the present invention to provide a drug delivery system and method to obviate or mitigate at least some of the above presented disadvantages.
SUMMARY OF THE INVENTION
The drug delivery systems of the present invention can provide for mixing various drugs in an optimally controlled manner, use flow controllers to guide multiple drugs into a single or into multiple catheters, enable a single lumen catheter to treat a specific region with several drugs, allow for dilution of a concentrated drug in order to both increase the time between refilling and also to provide any concentration of a drug that might be desired, provide for using a buffer fluid to deliver exact amounts of several drugs from the same catheter or to separate several drugs within a single catheter, use external fluid present in the human body either as a diluent or buffer fluid, and provide for a drug testing/filler apparatus to be used prior to implant to ensure proper function and easy means of filling multiple reservoirs with different fluids, and also after implant for refilling operations. The drug delivery system (DDS) can perform both bolus and continuous delivery of substances, and enable the measured delivery of any one of several drugs to one or more distal locations at independently programmable rates. New methods for using the DDS in the promotion of healthy pregnancy and treatment of a developing fetus are also possible.
According to a first aspect there is provided an implantable drug delivery device for controlling a dispensing of a fluid drug to an internal target site of a patient, the device comprising: a first reservoir for storing a first fluid; an input port in fluid communication with the first reservoir; an output port in fluid communication with the first reservoir; a flow control system for controlling the transfer of the first fluid between the respective ports and the first reservoir, the flow control system having at least one flow controller; and a flow control module for directing the at least one flow controller to direct the flow of the first fluid between a selected one of the ports and the first reservoir.
According to a further aspect there is provided a catheter assembly for directing a selected fluid to at least one target site of a patient, the assembly comprising: a first lumen having a first proximal end for coupling to a drug delivery device and a first distal end for positioning at the target site; a second lumen having a second proximal end for coupling to the drug delivery device and a second distal end for positioning at the target site, the first lumen and the second lumen adapted for fluid communication therebetween; a flow control system positioned at the first and second distal ends for directing inter-lumen fluid flow between the first and second lumens and for directing output fluid flow from the distal ends to the target site, the flow control system having at least one directional flow controller adapted to receive at least one control signal from the drug delivery device.
According to a still further aspect there is provided a method of outputting by a catheter assembly a selected fluid to a target site of a patient, the catheter assembly having a first lumen and a second lumen adapted for fluid communication therebetween and a flow control system for directing inter-lumen fluid flow between the first and second lumens and for directing output fluid flow from the distal ends of the lumens to the target site, the method comprising the steps of: delivering into the catheter at least two fluids, one of which is a buffer fluid, such that an alternating sequence of the fluids resides in the lumens; configuring by the flow control system the fluid flow of the lumens for inter-lumen fluid flow and inhibiting fluid flow output from the lumens; operating a pump in fluid communication with the lumens to perform inter-lumen circulation on the fluid sequence within the lumens until a selected one of the fluids resides near the distal tip of the first lumen; configuring by the flow control system to inhibit the inter-lumen fluid flow and to enable output fluid flow from the distal end of the first lumen of the selected fluid; and pumping the selected fluid as the output fluid from the first lumen.
According to a still further aspect there is provided an apparatus for configuring a drug delivery device, the device including at least one fluid reservoir in fluid communication with a fluid output port and a fluid input port and at least one fluid flow controller for controlling fluid input and output with respect to the fluid reservoir, the apparatus comprising; a fluid input component for recording an amount value of input fluid directed to the input port of the device from a fluid source; a flow control component for coupling to the device to configure the fluid flow controller to direct the input fluid from the input port into the fluid reservoir; a sensor component for recording at least one operational state value of the device including a fill state value of the reservoir; and a processor component for accepting user input commands and for coordinating the operation of the input, control, and sensor components in response to the user input commands; wherein the recorded values are provided to the user of the apparatus.
Accordingly, it is a feature of the present invention to provide for a drug delivery system which is capable of controlled delivery of both bolus and continuous flow of one or more substances, which may be substantially mixed or which may be presented sequentially, and which are delivered through a single catheter or through multiple catheters.
It is another feature of the present invention to provide for a drug delivery system which is capable of delivering more than one concentration of a substance, and perform dose titration by modifying either the concentration, or rate of dispensing, or both.
It is another feature of the present invention to provide for a drug delivery system which draws upon and utilizes a biological fluid available from the patient, rather than, or in addition to, a synthetic fluid, as an active drug, a buffer fluid, or a diluent, and thereby decreases the need for filling the drug delivery system from a source outside the body.
It is an advantage of the present invention to provide for a drug delivery system which is refillable with a diluent or buffer fluid which is a non-controlled (e.g., saline) rather than a controlled substance (e.g., narcotic), in order to facilitate drug delivery system use over time. For example, rather than refilling the drug delivery system with an analgesic agent, a diluent can be refilled which acts to dilute a very concentrated supply of analgesic drug which is stored in the drug delivery system.
It is another advantage of the present invention to provide for an implantable drug delivery system which provides for facilitating re-filling procedures by more often only requiring the replenishment of a single substance, which may be biologically inert, that is used as a buffer fluid or diluent, to efficiently dispense one or more drugs.
It is another feature of the present invention to provide for an implantable drug delivery system which uses flow controllers to enable the delivery of more than one substance through each of one or more catheters and also to allow each reservoir of the system to dispense fluid through each of several catheters.
It is another feature of the present invention to provide for an implantable drug delivery system which contains a mixing chamber capable of mixing two or more fluids to produce one or more concentrations of a drug and/or a mixture of several substances.
It is another feature of the present invention to provide for an embodiment of the implantable drug delivery system which is capable of improving delivery of a substance to a site which is relatively distal to the means for pumping, in part, by using at least one mixing chamber, in conjunction with diluent and buffer fluids.
It is another feature of the present invention to provide for an implantable drug delivery system which is capable of delivering more than one substance through each of one or more specific catheters.
It is a further feature of the present invention to provide for a multiple catheter implantable drug delivery system wherein each catheter is capable of independently delivering multiple medications to a single region at independently controlled times and rates.
It is a further feature of the present invention to provide an accessory which assists in filling, refilling, calibration, and testing of a drug delivery system which contains at least two fluids.
It is a further feature of the present invention to provide for a multiple lumen catheter which enables fluids dispensed by the drug delivery system to be circulated within the lumen so that a desired drug can be transported to its distal tip just prior to being delivered to a patient.
It is a further feature of the present invention to provide for a multiple stage catheter which contains at least two stages, wherein the first stage contains multiple lumen and a second stage only contains a single lumen, having a relatively small cross sectional volume as is desirable in some applications such as direct brain infusion.
It is a further feature of the present invention to facilitate a healthy birth process by delivering drugs to achieve for example: increasing the chance for conception, increasing the health of a developing fetus, assisting in normalizing fetal-placental flow or in compensating for abnormal flow, sensing the properties of the fluid in the vessels of the umbilical cord and using the properties of the fluids of the umbilical cord to guide the DDS dispensing or pumping operations, decreasing the risk of illness of the fetus, providing nutrients in response to lack of nutrients provided by the maternal sources, decreasing the unwanted effects of maternal exposure to substances that could be harmful to the fetus, in providing gene or germ therapy to the fetus, delivering therapeutic drugs in order to decrease the variability of the substances provided by the mother (e.g., as may occur when the mother has a metabolic disorder), decreasing the risk of infection or other viral or bacterial abnormality in the womb, decreasing the probability of premature labor, and assisting in extending the labor period.
Another feature of the present invention utilizes drug delivery to increase the likelihood of optimizing the health of the fetus. The drug delivery is directly to the fetus rather than to the mother, via a uterine target such as for example, the supporting vasculature, the placenta, or the vessels of the umbilical cord.
Another feature of the present invention uses a method which senses concentrations of substances in the umbilical artery or vein, the placenta, other structure of the fetal compartment, and evaluates this sensed data, and delivers drugs based upon this evaluation to a target in the fetal compartment or in the placenta in order to achieve a desired therapeutic result and/or in order to protect against a substance that could affect the fetus.
Another feature of the present invention uses a method which senses data from at least two sensors in the fetal compartment, in the maternal compartment, or in both compartments, and creates an input/output ratio or other index (which may be based upon a model) on which drug delivery to a uterine target or directly to the fetus, may be based.
Another feature of the present invention uses a method which senses intra-uterine, placental, umbilical (e.g., umbilical vein), amniotic and/or maternal levels of toxic substances (or substances which may become noxious when above certain levels), such as antidepressant drugs or their metabolites, and dispenses substances to counteract the effects that such unwanted substances may have for the fetus.
Another aspect of the present invention provides a method of using a drug delivery system for decreasing the risk of premature labor or miscarriage, by sensing physiological and chemical changes of the womb and delivering drugs to stop the process of premature labor or miscarriage (e.g., premature contractions), if either the physiological or chemical changes indicate that miscarriage may be beginning.
Further, another aspect of the present invention provides drug delivery to modify the content of breastmilk in order to optimally meet the needs of a developing infant. Sensing biological compounds in the milk or in the infants and then changing the drugs which are dispensed is not discussed in the prior art. The drug delivery system can deliver fluids to the mammary glands and related system of ducts and glandular tissue, in order to alter the content of the milk and other secretions, or in order to deliver fluids containing, for example, nutrients, immunoglobulin agents, hormones or synthetic hormonal analogs or antagonists or agonists, and other substances in order to modify the amount and content of milk that is produced and imbibed by the infant.
BRIEF DESCRIPTION OF THE FIGURES
These and other features of the preferred embodiments of the invention will become more apparent in the following detailed description in which reference is made to the appended drawings by way of example only, wherein:
FIG. 1 a shows an exemplary embodiment of a drug delivery device;
FIG. 1 b shows an alternative exemplary embodiment of the drug delivery device of FIG. 1 a;
FIG. 1 c shows an alternative exemplary embodiment of the drug delivery device of FIG. 1 a;
FIG. 2 shows a partial view of an exemplary embodiment of the drug delivery device of FIG. 1 a having a mixing chamber;
FIG. 3 shows an alternative exemplary embodiment of the drug delivery device of FIG. 2 , now with two mixing chambers;
FIG. 4 shows a variable volume embodiment of the mixing chamber of FIG. 2 ;
FIG. 5 shows an exemplary embodiment of the drug delivery device of FIG. 1 a;
FIG. 6 shows an exemplary embodiment of the drug delivery device of FIG. 1 a;
FIG. 7 a shows a dual-lumen catheter having a flow control at its distal end;
FIG. 7 b shows a further embodiment of the two-lumen catheter of FIG. 7 a;
FIG. 7 c shows a further embodiment of the two-lumen catheter of FIG. 7 b;
FIG. 7 d shows two single lumen catheters as an alternative embodiment of the two-lumen catheter of FIG. 7 b;
FIG. 8 shows the dual lumen catheter of FIG. 7 a with a pump flow controller;
FIG. 9 shows illustrative embodiments of multi-stage catheters with flow controllers;
FIG. 10 shows a DDS tester/calibrator/filling apparatus for use with the medical drug delivery device of FIG. 1 a;
FIG. 11 is a block diagram of a preferred embodiment of the control apparatus of FIG. 10 ;
FIG. 12 a shows an embodiment of a multiple catheter hub connection assembly (CHCA);
FIG. 12 b is shows a single catheter connection assembly (CCA) as a further embodiment of the assembly of FIG. 12 a;
FIG. 13 shows the DDS of FIG. 1 a implanted in the body of an implantee;
FIG. 14 shows a method for operating the device of FIG. 1 a;
FIG. 15 a shows one embodiment of a drug pump implanted in a mother for drug delivery to the fetus; and
FIG. 15 b shows one embodiment of a method of using the drug pump to treat the fetus.
DETAILED DESCRIPTION
The medical drug delivery system (DDS) is an apparatus which is part of a system that dispenses drugs into any region of the implantee, including the body, organs, brain, vasculature and areas related to reproduction. The terms âdrugâ, âmedicationâ, âactive agentâ, or âfluidâ can all be used to mean a therapeutic agent delivered with the goal of producing a desired effect. The drug may often be stored within the DDS in the form of a fluid or gel, however, the DDS can also contain powder forms of drugs which are mixed with, dissolved or suspended within fluids prior dispensing them to an implantee. The types of fluids which can be delivered by the DDS include, but are not limited to, medications, vitamins, nutrients, chemicals, antibiotics, hormones or hormonal drugs, catalysts, gene/germ therapies, anticoagulants, chemotherapeutics, antigens, anti-tumor agents, analgesic, anti-inflammatory agents, antioxidants, parasiticides, and others. Other drugs which can be delivered are listed in prior art (e.g., U.S. Pat. Nos. 5,980,508, 6,571,125 & US 2003/0093063 A1, & US2003/0130645 A1, which are incorporated by reference herein). The DDS can deliver fluids that contain nanoparticles or that activate drugs or nanoparticles (termed âcatalystsâ), and/or cause the membranes of the nanoparticles to disintegrate and release drugs. The DDS can emit light or energy at a particular frequency within its internal components (e.g., via a non-thermal laser generator located in the mixing chamber), within its catheters, or from the tip of the catheters in order to activate, for example, photosensitive drugs/nanoparticles that are contained within the fluids it releases to various targets (e.g., porfimer sodium, Photofrin, Verteporfin). Nanoparticles (and the similar âmicroemulsionsâ and microfabricated particles) can contain substances such as medications, and can, for example, be introduced into the body to move along in the bloodstream toward their targets, or can be delivered locally.
The types of medical conditions that the DDS might be used to treat include, but are not limited to cardiovascular abnormalities and diseases, arthritis, pain disorders, disorders of the spine, neurological or psychiatric pathology, migraine disorders, fetal disorders, infections, cancer, diabetes, systemic illnesses, biological and metabolic abnormalities requiring treatment. The DDS can be used in medical, contraceptive, gynecological, pharmaceutical, veterinary, and research applications. Additionally, the DDS can be implanted in a mother and instead of, or in addition to, delivering drugs to the mother, can deliver drugs directly to a developing fetus, or into the umbilical cord, or to an area near the fetus (e.g. the amniotic fluid) in order to provide drug to the fetus or in order to effect a therapeutic change in that area. The DDS can also be used to change the characteristics of the breastmilk so that therapy can be achieved after birth.
Terminology used herein is for illustration and convenience only and is not to be taken as a limitation of the invention. Words such as âupperâ, âlowerâ, or âdownwardâ can be used to describe embodiments shown in the figures. However, the components of the DDS can be oriented and configured in many directions and the terminology should be understood as encompassing such variations unless specified otherwise. More specifically, âupstreamâ or âproximalâ refer to a point in the fluid path that is closer to reservoirs while âdownstreamâ or âdistalâ refer to a point in the flow pathway which is operationally closer to point at which the fluid will be delivered to the implantee. Operating components in a âforwardâ direction causes fluid to move distally while causing fluid to travel in a âreverseâ direction signifies moving fluid upstream towards the reservoirs. Further the illustrations are not drawn to scale, and the various components can be different shapes and sizes as long as the function does not deviate from the structures illustrated in the figures. For example, the width (i.e., internal circumference) of the lumens of the catheters may be much smaller than those which are shown here, or may vary in their width at different points (e.g., at their distal tips), but in order to illustrate internal components of the catheters, the catheters were shown with large internal widths.
Turning to FIG. 1 a , an implantable DDS 10 is shown. In this exemplary embodiment, the internal components of the system 10 are enclosed in an implantable housing 12 which may be made of titanium with a plastic outer coating. Within the housing 12 , is located fluid containment means which is realized in FIG. 1 a by a first reservoir 14 a and second reservoir 14 b , which are connected to a catheter hub 16 or output port. The catheter hub 16 allows a catheter to be attached to the DDS. For example, catheters can be slipped over, or screwed onto, the hubs, or the DDS can be manufactured with the catheters glued to or formed upon the catheter hubs. In this specification, a catheter refers to a single lumen through which fluid may travel. In the case of a multiple lumen catheter, each lumen can be connected to a separate catheter hub. The first reservoir 14 a is connected to the catheter hub 16 by a fluid channel 18 a , which in this example, is realized by a connection tube. The fluid channel 18 a allows fluid to travel from the first reservoir 14 a to the catheter hub 16 (or to an intervening internal component such as a mixing chamber 40 âsee FIG. 2 âwhich it enters prior to arriving at the catheter hub 16 ) and fluid channel 18 a may be formed as part of the reservoir 14 a . The second reservoir 14 b is also connected to the catheter hub 16 by fluid channel 18 b , which in this case is also a connection tube. The first and second reservoirs 14 a - b can also be referred to as âRes1â and âRes2â, respectively. Flow from Res1 14 a through the fluid channel 18 b to the catheter hub 16 is controlled by the control apparatus (labeled as âCAâ in the figures and also referred to as flow control module) 22 which controls flow by operating one or more pumps to cause fluid to flow and also manipulating the state of flow controllers (e.g., 20 a - b ) to control the path through which this fluid may travel. For example, the control apparatus can deliver fluid from Res1 14 a by operating a pump 23 so that fluid is pushed out of Res1 14 a and changing the state of flow controller 20 a for the Res1 14 a in order to control the flow of fluid, which in this case entails permitting fluid to flow from Res1 14 a to the catheter hub 16 . The flow controller 20 b for Res2 14 b is also shown.
Sensors such as the sensor 21 placed in the catheter hub 16 can measure the rates at which fluids travel, or âflow rateâ and send this information to the control apparatus 22 . The term âsensorâ can refer to a sensor placed anywhere, either within or outside of the DDS housing, which provides sensed data relating to physical, chemical, physiological or other measurements relating to DDS operation, drug delivery, or the implantee. Sensors of the DDS can also include electrical (e.g., to measure the amount of residual charge in power supply, current flow, or impedance), chemical, optical, thermal, flow, volume, position, pressure, gas, oxygen, and biosensors or other types of sensors. A sensor may provide sensed data relating to multiple characteristics, for example, the flow rate, concentration, and pressure of a fluid which is being delivered by the DDS. Accordingly, a sensor may be an aggregate of several types of specialized structures each configured to sense a different fluid characteristic of the environment in which it is located.
The sensors utilized by the DDS can include, but are not limited to, electrical (e.g., EKG electrode), chemical (e.g., pH), electrochemical sensors (e.g., microelectrode arrays made by Quanteon for measuring substances such as glutamate), or optical sensors (e.g., which can detect O2, CO2, and PH levels, and which can take the form of pulse oximeters or chromophore-based IO biosensors having one or more sensing fibers), and can detect physical measures (e.g., pressure, temperature, flow, acceleration), enzymatic changes, or the state of tissue or an organ. The sensors can be biosensors which are capable of sensing one or more specific molecules or other biological substances, either directly or by means of their metabolites. As is known to those in the art, sensor technology is continually advancing, however, some types of sensors which may be used are now described. The sensors can be similar to, based upon, or incorporate, nanotechnology such as Nanogen's NanoChipâ¢. Electronic Microarray, which uses a tiny, silicon chip that is capable of rapid identification and precise analysis of biological molecules. Additionally, an interaction between molecules may also be identified by using real-time BIA (Biomolecular Interaction Analysis, Pharmacia Biosensor AB) which detects surface plasmon resonance (SPR), an optical phenomenon. Detection depends on changes in the mass concentration of macromolecules at the biospecific interface, and does not require any labeling of interactants. U.S. Pat. No. 5,791,344 to Schulman et al. entitled âPatient Monitoring System,â proposes a system to monitor the concentration of a substance in a subject's blood wherein one enzymatic sensor is inserted into a patient to monitor glucose. Similarly, EP1011797 to Schulman et al, entitled âSystem of Implantable Devices for Monitoring or Affecting Body Parameters,â proposes using microsensors to measure, for example, glucose level, oxygen content, temperature, and other measures. There are also a number of implantable medical devices and systems which monitor physiological data associated with the heart via telemetry (e.g., U.S. Pat. No. 5,720,771 to Snell entitled, âMethod and Apparatus for Monitoring Physiological Data From an Implantable Medical Deviceâ). Additionally, US application 20030171711, entitled âClosed-loop drug delivery systemâ employs a chromophore-based IO biosensor having one or more sensing fibers implanted directly into patient tissue. The contents of these prior art examples are hereby incorporated by reference as if recited in full herein. When possible, the DDS can rely upon completely implanted sensors, but may also communicate with, external devices, or may utilize information derived from assays, or laboratory techniques, in order to obtain accurate sensed data of the desired measures.
The term âflow controllerâ can refer to one or more valves (e.g., a piston, umbrella, disc, poppet, duckbill, ball, flapper, shuttle, gate, or other type of mechanism which functions as a valve to halt or redirect flow) which have at least one âopenâ state where fluid may pass, and a âclosedâ state where fluid may not pass. The flow controller, generically referenced as reference numeral 20 , can use more than one type of valve or mechanism to control flow within, into, and out of the DDS and its catheters. The flow controller can also incorporate a pump to actuate a direction and/or magnitude of the fluid flow within, into, and out of the DDS. Accordingly, the term âflow controllerâ can include one or more valves and/or pumps. In an âopenâ state the flow controller may use several valves some of which are open and some of which are closed to direct fluid along a specific path, and accordingly the âopenâ state refers to whether a particular fluid path is âopenâ, allowing fluid to pass or âclosedâ, inhibiting fluid from passing. The flow controller can take the form of a âhubâ structure which receives fluid from at least one source at its proximal port(s) and direct this fluid to one or more target paths through its distal ports. The number of proximal ports can be less than, equal to, or greater than the number of distal ports. One example of a flow controller which utilizes a hub type of structure is shown in FIG. 9 . Depending upon the pumping operations of the DDS, the fluids can travel through the hub in a proximal-to-distal direction, or vice-versa (i.e., the flow control hubs can guide fluids bi-directionally). Flow controllers can be passive in that one fluid channel (e.g. a connection tube) can be continuously connected to several fluid channels (via, for example, a manifold), or can be active in that fluid path is dynamically determined by the state of one or more valves. Alternatively, the flow controller can control flow by exerting pressure upon the fluid channel (which may be a deformable, flexible, tube) in order to cause a specific portion to collapse, thereby halting flow.
The flow controllers of the DDS can be realized using different types of mechanisms which are described in the prior art and which are currently used in implantable pump devices. For example, US 2002/0193751 A1, incorporated herein by reference, discloses flow controllers, such as flow diverter or flow regulator based upon one of the following: a rod element, a pump, a solenoid, or a rotatable valve, which may or may not have a diversion conduit, a deformable conduit which may be squeezed shut by gas or hydraulic, pressure. However, in this art, these flow controllers are used to divert fluid in order to provide a simple mechanism for adjusting the rate of drug flow, rather than to halt flow, to send fluids to different catheter hubs thereby allowing different reservoirs to send fluid to different catheter hubs, and to isolate different fluids, as occurs in the DDS described here. U.S. Pat. No. 5,643,247, incorporated by reference herein, includes microparticle switching devices for stopping or redirecting flow, or for use as mechanical actuators or minipumps, and which can be used in the DDS, including the catheters (e.g., at either proximal and distal ends, and, for example, to accomplish inter-lumen flow control or circulation of a fluid circuit). The plurality of flow controllers 20 for the DDS is referred to collectively as a flow control system operated by the flow control module 22 as described herein.
The states of the flow controllers
20 a , 20 b can be determined by the control apparatus 22 or flow control module. Alternatively, rather than the state of the flow controllers
20 a , 20 b being controlled by the control apparatus 22 , the state can be pressure sensitive, for example, the flow controller can enter an open state only when positive pressure on one side is more than a specified amount. This type of pressure sensitive control of the flow controller can not be used when a reservoir serves more than one catheter hub since operating the pumping means for a reservoir and creating a pressure increase would set flow controllers
20 a , 20 c for both catheter hubs
16 a , 16 b to their open states and controlled delivery of fluid from only one catheter would not be realizable (e.g., see FIG. 1 c ). The states of the flow controllers enable the DDS to route fluids within its internal components. For example, flow controllers 20 a,b are operated by the control apparatus 22 to control the flow of fluids so that these may travel from each reservoir 14 a,b to a specific catheter hub 16 a . Flow controllers (e.g. 20 r ) also allow for the control of fluid flow during filling and refilling operations. Any set of mechanisms which enable the flow of fluid to be controlled so that it is encouraged or inhibited from flowing along one or more fluid paths is understood to be a fluid âflow controllerâ. In the embodiment shown in FIG. 1 a the fluid flow controller is realized by the control apparatus and the flow controllers whose states it determines in order to direct the flow of fluids along the different fluid channels of the drug delivery device DDS.
The DDS is filled in order to provide the fluid for subsequent drug delivery. At least one replenishment mechanism is incorporated into the DDS which serves to securely join with an external fluid source connector so that the DDS can be filled with fluids. In FIG. 1 a , a replenishment mechanism is shown which is comprised of an inlet/ input port 24 which resides in the housing 12 , and which includes a re-sealable port 26 or âseptumâ, which is designed to make a secure connection with an external fluid source connector (e.g., the septum may be punctured by catheter which terminates with a syringe). The inlet port 24 allows fluid to travel through the inlet port fluid channel 18 r , when permitted by a flow controller 20 r for regulating flow of fluid from the inlet port to internal components of the DDS ( e.g. reservoirs 14 a,b , channels 18 a,b,r ). In FIG. 1 a the inlet port fluid channel 18 r allows fluid to travel from the inlet port 24 to the <figure-callout id="16" label="catheter hub" filenames="US09919102-20180320-
CLAIMS
Claims ( 20 )
I claim:
1. A drug delivery system for delivering a drug into a patient, the apparatus comprising:
an implantable drug pump having at least one drug reservoir filled with a drug and pumping means, the drug pump further configured to be operated jointly with a catheter assembly in order to provide controlled delivery of said drug to said catheter assembly;
a catheter assembly configured for operating in conjunction with the implantable drug pump and for providing circular flow of a therapeutic fluid therethrough, the therapeutic fluid comprising a first volume of a fluid and a drug contained therein;
a flow controller under control of the implantable drug pump for controlling a flow rate of the therapeutic fluid within the catheter assembly; and
a distal catheter member configured for operating to selectively permit: the therapeutic fluid to do at least one of the following selected from the group of: a) circulate, and b) be dispensed to a predetermined location in the patient.
2. The drug delivery system of claim 1 , wherein the catheter assembly comprises:
a first lumen having a first proximal end for coupling to a drug delivery device and a first distal end for positioning at the target site;
a second lumen having a second proximal end for coupling to the drug delivery device and a second distal end for positioning at the target site, the first lumen and the second lumen adapted for fluid communication therebetween;
a flow control system positioned at the first and second distal ends for directing inter-lumen fluid flow between the first and second lumens and for directing output fluid flow from the distal ends to the target site, the flow control system having at least one directional flow controller adapted to receive at least one control signal from the drug delivery device.
3. The assembly of claim 2 further comprising the flow control system having a plurality of the directional flow controllers.
4. The assembly of claim 3 , wherein the flow controllers are each responsive to the control signals from the drug delivery device.
5. The assembly of claim 4 , wherein the control signals configure the plurality of the flow controllers in an output flow open state and an inter-lumen flow closed state, such that inter-lumen fluid flow is inhibited and output fluid flow is enabled from at least one of the lumens.
6. The assembly of claim 4 , wherein the control signals configure the plurality of the flow controllers in an output flow closed state and an inter-lumen flow open state, such that output fluid flow is inhibited and inter-lumen fluid flow is enabled between the lumens.
7. The assembly of claim 3 , wherein the plurality of the directional flow controllers further comprises a first directional flow controller and a second directional flow controller.
8. The assembly of claim 7 , wherein the open state of the first directional flow controller provides for inter-lumen fluid flow simultaneously with the closed state of the second directional flow controller inhibiting the output fluid flow.
9. The assembly of claim 7 , wherein the first directional flow controller is associated with the first lumen and the second directional flow controller is associated with the second lumen, such that the first and second flow controllers cooperate to inhibit respective output fluid flow from each of the lumens while providing for inter-lumen fluid flow.
10. The assembly of claim 2 , wherein the first lumen and the second lumen are selected from the group comprising: a dual lumen catheter; and individual segments of a single lumen catheter.
11. The assembly of claim 2 , which additionally includes at least one of the following:
a pump in fluid communication with the lumens and the drug delivery device and configured to accomplish at least one of the following: to pump fluid from the drug delivery device into either of the two lumens, to pump fluid out of either of the two lumens and into the drug delivery device, and to circulate fluids within the lumens; and a sensor for sensing at least one physical property of at least one fluid, said property including at least one of the following, a color, a chemical, a concentration.
12. The assembly of claim 2 wherein the assembly is part of a multi-stage catheter and wherein a second catheter is attached to the distal end of the lumens and receives the fluid from the flow control system causing said fluid to flow through said second catheter prior to delivery to said patient.
13. The assembly of claim 2 , wherein said flow control system incorporates at least one of the following: a pump, a second drug delivery device which is realized within a microchip, and sensors.
14. The drug delivery system of claim 1 wherein the fluid is fluid endogenous to the patient.
15. The drug delivery system of claim 1 wherein the fluid is a diluent.
16. The drug delivery system of claim 1 wherein the fluid is a pusher fluid.
17. The drug delivery system of claim 1 wherein the catheter assembly comprises a closed loop of lumen defining at least one sealed channel.
18. The drug delivery system of claim 1 wherein the catheter assembly comprises a closed loop of lumen defining at least one sealed fluid circuit.
19. The drug delivery system of claim 1 wherein the catheter assembly comprises a double-lumen catheter.
20. The drug delivery system of claim 1 wherein concentration of the drug in the therapeutic fluid varies in different portions of the catheter assembly.
US14/070,522
2003-07-16
2013-11-02
Medical drug delivery systems and methods for delivery of multiple fluids and concentrations
Expired - Fee Related
US9919102B2
( en )
Priority Applications (3)
Application Number
Priority Date
Filing Date
Title
US14/070,522
US9919102B2
( en )
2003-07-16
2013-11-02
Medical drug delivery systems and methods for delivery of multiple fluids and concentrations
US15/925,723
US10589024B2
( en )
2003-07-16
2018-03-19
Medical drug delivery systems with mixing chamber
US16/820,634
US20200222628A1
( en )
2003-07-16
2020-03-16
Medical Drug Delivery Systems
Applications Claiming Priority (7)
Application Number
Priority Date
Filing Date
Title
US48813303P
2003-07-16
2003-07-16
US57419504P
2004-05-25
2004-05-25
US58787004P
2004-07-15
2004-07-15
PCT/CA2004/001033
WO2005007223A2
( en )
2003-07-16
2004-07-16
Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations
US10/893,414
US7811279B2
( en )
2003-07-16
2004-07-19
Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations
US12/853,941
US8591498B2
( en )
2003-07-16
2010-08-10
Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations
US14/070,522
US9919102B2
( en )
2003-07-16
2013-11-02
Medical drug delivery systems and methods for delivery of multiple fluids and concentrations
Related Parent Applications (1)
Application Number
Title
Priority Date
Filing Date
US12/853,941
Continuation
US8591498B2
( en )
2003-07-16
2010-08-10
Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations
Related Child Applications (1)
Application Number
Title
Priority Date
Filing Date
US15/925,723
Continuation
US10589024B2
( en )
2003-07-16
2018-03-19
Medical drug delivery systems with mixing chamber
Publications (2)
Publication Number
Publication Date
US20150018758A1
US20150018758A1 ( en )
2015-01-15
US9919102B2
true
US9919102B2 ( en )
2018-03-20
Family
ID=43307036
Family Applications (6)
Application Number
Title
Priority Date
Filing Date
US10/893,414
Expired - Fee Related
US7811279B2
( en )
2003-07-16
2004-07-19
Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations
US11/160,949
Abandoned
US20060204532A1
( en )
2003-07-16
2005-07-15
Drug Delivery Systems and Methods for Modulating the Fetal Environment and Pregnancy Process
US12/853,941
Expired - Fee Related
US8591498B2
( en )
2003-07-16
2010-08-10
Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations
US14/070,522
Expired - Fee Related
US9919102B2
( en )
2003-07-16
2013-11-02
Medical drug delivery systems and methods for delivery of multiple fluids and concentrations
US15/925,723
Expired - Fee Related
US10589024B2
( en )
2003-07-16
2018-03-19
Medical drug delivery systems with mixing chamber
US16/820,634
Abandoned
US20200222628A1
( en )
2003-07-16
2020-03-16
Medical Drug Delivery Systems
Family Applications Before (3)
Application Number
Title
Priority Date
Filing Date
US10/893,414
Expired - Fee Related
US7811279B2
( en )
2003-07-16
2004-07-19
Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations
US11/160,949
Abandoned
US20060204532A1
( en )
2003-07-16
2005-07-15
Drug Delivery Systems and Methods for Modulating the Fetal Environment and Pregnancy Process
US12/853,941
Expired - Fee Related
US8591498B2
( en )
2003-07-16
2010-08-10
Programmable medical drug delivery systems and methods for delivery of multiple fluids and concentrations
Family Applications After (2)
Application Number
Title
Priority Date
Filing Date
US15/925,723
Expired - Fee Related
US10589024B2
( en )
2003-07-16
2018-03-19
Medical drug delivery systems with mixing chamber
US16/820,634
Abandoned
US20200222628A1
( en )
2003-07-16
2020-03-16
Medical Drug Delivery Systems
Country Status (2)
Country
Link
US
( 6 )
US7811279B2
( en )
WO
( 1 )
WO2005007223A2
( en )
Cited By (5)
* Cited by examiner, â Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
US11745003B2
( en )
2020-10-30
2023-09-05
Medtronic, Inc.
Implantable access port with one-directional filter
US11931545B2
( en )
2020-10-30
2024-03-19
Medtronic, Inc.
Drug infusion port
US11992642B2
( en )
2020-10-30
2024-05-28
Medtronic, Inc.
Implantable medical device for delivery of pharmacological agents to the deep brain structures
US12226609B2
( en )
2020-12-16
2025-02-18
Medtronic, Inc.
Method to detect inadvertent delivery of drug to a subcutaneous pocket
US12551613B2
( en )
2020-10-30
2026-02-17
Medtronic, Inc.
Implantable drug delivery port
Families Citing this family (647)
* Cited by examiner, â Cited by third party
Publication number
Priority date
Publication date
Assignee
Title
US6872187B1
( en )
1998-09-01
2005-03-29
Izex Technologies, Inc.
Orthoses for joint rehabilitation
US7416537B1
( en )
1999-06-23
2008-08-26
Izex Technologies, Inc.
Rehabilitative orthoses
US8914114B2
( en )
2000-05-23
2014-12-16
The Feinstein Institute For Medical Research
Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation
US20080172026A1
( en )
2006-10-17
2008-07-17
Blomquist Michael L
Insulin pump having a suspension bolus
WO2004058337A1
( en )
2002-12-23
2004-07-15
Medtronic, Inc.
Multiple infusion section catheters, systems, and methods
US8246602B2
( en )
2002-12-23
2012-08-21
Medtronic, Inc.
Catheters with tracking elements and permeable membranes
US8043281B2
( en )
2002-12-23
2011-10-25
Medtronic, Inc.
Catheters incorporating valves and permeable membranes
US8771183B2
( en )
2004-02-17
2014-07-08
Abbott Diabetes Care Inc.
Method and system for providing data communication in continuous glucose monitoring and management system
AU2003303597A1
( en )
2002-12-31
2004-07-29
Therasense, Inc.
Continuous glucose monitoring system and methods of use
EP1617758A1
( en )
*
2003-04-16
2006-01-25
Université Libre De Bruxelles
A non-invasive sensor to visually analyze the level of muscle activity
AU2004232858B2
( en )
2003-04-23
2009-07-09
Mannkind Corporation
Hydraulically actuated pump for long duration medicament administration
US8066639B2
( en )
2003-06-10
2011-11-29
Abbott Diabetes Care Inc.
Glucose measuring device for use in personal area network
US20190357827A1
( en )
2003-08-01
2019-11-28
Dexcom, Inc.
Analyte sensor
US8777889B2
( en )
*
2004-06-15
2014-07-15
Ceramatec, Inc.
Apparatus and method for administering a therapeutic agent into tissue
US8066659B2
( en )
*
2004-06-15
2011-11-29
Ceramatec, Inc.
Apparatus and method for treating and dispensing a material into tissue
US7615030B2
( en )
*
2003-10-06
2009-11-10
Active O, Llc
Apparatus and method for administering a therapeutic agent into tissue
US8065161B2
( en )
2003-11-13
2011-11-22
Hospira, Inc.
System for maintaining drug information and communicating with medication delivery devices
US9123077B2
( en )
2003-10-07
2015-09-01
Hospira, Inc.
Medication management system
US10912712B2
( en )
2004-03-25
2021-02-09
The Feinstein Institutes For Medical Research
Treatment of bleeding by non-invasive stimulation
US9011329B2
( en )
2004-04-19
2015-04-21
Searete Llc
Lumenally-active device
US8353896B2
( en )
2004-04-19
2013-01-15
The Invention Science Fund I, Llc
Controllable release nasal system
US8512219B2
( en )
2004-04-19
2013-08-20
The Invention Science Fund I, Llc
Bioelectromagnetic interface system
US7850676B2
( en )
*
2004-04-19
2010-12-14
The Invention Science Fund I, Llc
System with a reservoir for perfusion management
WO2006014425A1
( en )
2004-07-02
2006-02-09
Biovalve Technologies, Inc.
Methods and devices for delivering glp-1 and uses thereof
US8313433B2
( en )
2004-08-06
2012-11-20
Medtronic Minimed, Inc.
Medical data management system and process
US7393181B2
( en )
2004-09-17
2008-07-01
The Penn State Research Foundation
Expandable impeller pump
WO2006055547A2
( en )
2004-11-15
2006-05-26
Izex Technologies, Inc.
Instrumented orthopedic and other medical implants
US8308794B2
( en )
2004-11-15
2012-11-13
IZEK Technologies, Inc.
Instrumented implantable stents, vascular grafts and other medical devices
WO2006073484A2
( en )
2004-12-27
2006-07-13
North Shore-Long Island Jewish Research Institute
Treating inflammatory disorders by electrical vagus nerve stimulation
US11207518B2
( en )
2004-12-27
2021-12-28
The Feinstein Institutes For Medical Research
Treating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway
US9788771B2
( en )
2006-10-23
2017-10-17
Abbott Diabetes Care Inc.
Variable speed sensor insertion devices and methods of use
US7697967B2
( en )
2005-12-28
2010-04-13
Abbott Diabetes Care Inc.
Method and apparatus for providing analyte sensor insertion
US9636450B2
( en )
2007-02-19
2017-05-02
Udo Hoss
Pump system modular components for delivering medication and analyte sensing at seperate insertion sites
US20060181695A1
( en )
*
2005-02-11
2006-08-17
Sage Burton H Jr
Compensating liquid delivery system and method
US8956291B2
( en )
2005-02-22
2015-02-17
Admetsys Corporation
Balanced physiological monitoring and treatment system
US8912908B2
( en )
2005-04-28
2014-12-16
Proteus Digital Health, Inc.
Communication system with remote activation
CN102379684B
( en )
2005-04-28
2014-11-19
æ®ç½éæ¯æ°åä¿å¥å ¬å¸
Pharma-informatics system
US8836513B2
( en )
2006-04-28
2014-09-16
Proteus Digital Health, Inc.
Communication system incorporated in an ingestible product
US8802183B2
( en )
2005-04-28
2014-08-12
Proteus Digital Health, Inc.
Communication system with enhanced partial power source and method of manufacturing same
US8730031B2
( en )
2005-04-28
2014-05-20
Proteus Digital Health, Inc.
Communication system using an implantable device
US9198608B2
( en )
2005-04-28
2015-12-01
Proteus Digital Health, Inc.
Communication system incorporated in a container
US20090076485A1
( en )
*
2005-04-29
2009-03-19
Mubarak Kamal K
Alarm system for implantable pumps for intravenous drug delivery
US8211060B2
( en )
2005-05-10
2012-07-03
Palyon Medical (Bvi) Limited
Reduced size implantable pump
US8915893B2
( en )
2005-05-10
2014-12-23
Palyon Medical (Bvi) Limited
Variable flow infusion pump system
US7637892B2
( en )
2005-05-10
2009-12-29
Palyon Medical (Bvi) Limited
Variable flow infusion pump system
US8114055B2
( en )
2005-05-10
2012-02-14
Palyon Medical (Bvi) Limited
Implantable pump with infinitely variable resistor
US8034030B2
( en )
2005-05-25
2011-10-11
Palyon Medical (Bvi) Limited
Multi-reservoir implantable pump with variable flow rate capabilities
US8002747B2
( en )
2005-05-26
2011-08-23
The Alfred E. Mann Foundation For Scientific Research
Implantable infusion device with multiple controllable fluid outlets
FR2888518B1
( en )
*
2005-07-12
2007-10-05
Rosatech Sa
HOMOGENEOUS MIXING AND DISTRIBUTION OF A REACTANT ON A SURFACE
US20070066956A1
( en )
*
2005-07-27
2007-03-22
Medtronic Minimed, Inc.
Systems and methods for entering temporary basal rate pattern in an infusion device
US8353906B2
( en )
*
2005-08-01
2013-01-15
Ceramatec, Inc.
Electrochemical probe and method for in situ treatment of a tissue
US7783095B2
( en )
*
2005-08-11
2010-08-24
Siemens Medical Solutions Usa, Inc.
System and method for fetal biometric measurements from ultrasound data and fusion of same for estimation of fetal gestational age
US8965509B2
( en )
2005-08-31
2015-02-24
Michael Sasha John
Methods and systems for semi-automatic adjustment of medical monitoring and treatment
US20080288023A1
( en )
*
2005-08-31
2008-11-20
Michael Sasha John
Medical treatment using patient states, patient alerts, and hierarchical algorithms
CA2620586A1
( en )
2005-08-31
2007-03-08
Boris P. Kovatchev
Improving the accuracy of continuous glucose sensors
US9089713B2
( en )
*
2005-08-31
2015-07-28
Michael Sasha John
Methods and systems for semi-automatic adjustment of medical monitoring and treatment
EP1920418A4
( en )
2005-09-01
2010-12-29
Proteus Biomedical Inc
IMPLANTABLE WIRELESS COMMUNICATION SYSTEM
DE102005045393B4
( en )
*
2005-09-23
2017-01-05
Drägerwerk AG & Co. KGaA
Method for dosing solutions
US8880138B2
( en )
2005-09-30
2014-11-04
Abbott Diabetes Care Inc.
Device for channeling fluid and methods of use
US7766829B2
( en )
2005-11-04
2010-08-03
Abbott Diabetes Care Inc.
Method and system for providing basal profile modification in analyte monitoring and management systems
US8936590B2
( en )
2005-11-09
2015-01-20
The Invention Science Fund I, Llc
Acoustically controlled reaction device
US8273071B2
( en )
*
2006-01-18
2012-09-25
The Invention Science Fund I, Llc
Remote controller for substance delivery system
US8617141B2
( en )
2005-11-09
2013-12-31
The Invention Science Fund I, Llc
Remote controlled in situ reaction device
US7699834B2
( en )
2005-11-09
2010-04-20
Searete Llc
Method and system for control of osmotic pump device
US8083710B2
( en )
*
2006-03-09
2011-12-27
The Invention Science Fund I, Llc
Acoustically controlled substance delivery device
US9067047B2
( en )
2005-11-09
2015-06-30
The Invention Science Fund I, Llc
Injectable controlled release fluid delivery system
US20070106271A1
( en )
*
2005-11-09
2007-05-10
Searete Llc, A Limited Liability Corporation
Remote control of substance delivery system
US8992511B2
( en )
2005-11-09
2015-03-31
The Invention Science Fund I, Llc
Acoustically controlled substance delivery device
US20070118078A1
( en )
*
2005-11-18
2007-05-24
Mcnally David J
Method and apparatus for controlled feeding of an infant
DE102005056310B4
( en )
*
2005-11-25
2017-02-02
Drägerwerk AG & Co. KGaA
Method and device for monitoring infusions
US20070219488A1
( en )
*
2005-12-16
2007-09-20
Darius Francescatti
Active drainage system for use in defined natural or surgically created body cavities or lumina
US11298058B2
( en )
2005-12-28
2022-04-12
Abbott Diabetes Care Inc.
Method and apparatus for providing analyte sensor insertion
FR2895667B3
( en )
*
2006-01-05
2008-04-04
Rene Vinci
FERTILITY DETECTOR FOR MAMMALS
US7713226B2
( en )
*
2006-01-06
2010-05-11
Renal Solutions, Inc.
On demand and post-treatment delivery of saline to a dialysis patient
US7736310B2
( en )
2006-01-30
2010-06-15
Abbott Diabetes Care Inc.
On-body medical device securement
US7708730B2
( en )
2006-01-30
2010-05-04
Palyon Medical (Bvi) Limited
Template system for multi-reservoir implantable pump
US7942818B2
( en )
*
2006-02-01
2011-05-17
University Of Florida Research Foundation, Inc.
Obstetric analgesia system
GB0603037D0
( en )
*
2006-02-15
2006-03-29
Renishaw Plc
Implantable fluid distribution device and a method of drug delivery
US7981034B2
( en )
2006-02-28
2011-07-19
Abbott Diabetes Care Inc.
Smart messages and alerts for an infusion delivery and management system
US7885698B2
( en )
2006-02-28
2011-02-08
Abbott Diabetes Care Inc.
Method and system for providing continuous calibration of implantable analyte sensors
US7826879B2
( en )
2006-02-28
2010-11-02
Abbott Diabetes Care Inc.
Analyte sensors and methods of use
US20080140057A1
( en )
2006-03-09
2008-06-12
Searete Llc, A Limited Liability Corporation Of State Of The Delaware
Injectable controlled release fluid delivery system
JP2009530041A
( en )
2006-03-23
2009-08-27
ã¶ã»ãã³ã»ã¹ãã¼ãã»ãªãµã¼ãã»ãã¡ã³ãã¼ã·ã§ã³
Cardiac assist device with expandable impeller pump
ITMO20060097A1
( en )
*
2006-03-24
2007-09-25
Giuseppe Zucca
DEVICE AND METHOD FOR DILUTION AND PREPARATION OF ANTIBLASTIC DRUGS
AU2007233231B2
( en )
*
2006-03-30
2011-02-24
Mannkind Corporation
Multi-cartridge fluid delivery device
US7620438B2
( en )
2006-03-31
2009-11-17
Abbott Diabetes Care Inc.
Method and system for powering an electronic device
US8346335B2
( en )
2008-03-28
2013-01-01
Abbott Diabetes Care Inc.
Analyte sensor calibration management
US8473022B2
( en )
2008-01-31
2013-06-25
Abbott Diabetes Care Inc.
Analyte sensor with time lag compensation
US8374668B1
( en )
2007-10-23
2013-02-12
Abbott Diabetes Care Inc.
Analyte sensor with lag compensation
US7630748B2
( en )
2006-10-25
2009-12-08
Abbott Diabetes Care Inc.
Method and system for providing analyte monitoring
US8478557B2
( en )
2009-07-31
2013-07-02
Abbott Diabetes Care Inc.
Method and apparatus for providing analyte monitoring system calibration accuracy
US7653425B2
( en )
2006-08-09
2010-01-26
Abbott Diabetes Care Inc.
Method and system for providing calibration of an analyte sensor in an analyte monitoring system
US8140312B2
( en )
2007-05-14
2012-03-20
Abbott Diabetes Care Inc.
Method and system for determining analyte levels
US9392969B2
( en )
2008-08-31
2016-07-19
Abbott Diabetes Care Inc.
Closed loop control and signal attenuation detection
US8226891B2
( en )
2006-03-31
2012-07-24
Abbott Diabetes Care Inc.
Analyte monitoring devices and methods therefor
US7618369B2
( en )
2006-10-02
2009-11-17
Abbott Diabetes Care Inc.
Method and system for dynamically updating calibration parameters for an analyte sensor
US9675290B2
( en )
2012-10-30
2017-06-13
Abbott Diabetes Care Inc.
Sensitivity calibration of in vivo sensors used to measure analyte concentration
US8224415B2
( en )
2009-01-29
2012-07-17
Abbott Diabetes Care Inc.
Method and device for providing offset model based calibration for analyte sensor
US8219173B2
( en )
2008-09-30
2012-07-10
Abbott Diabetes Care Inc.
Optimizing analyte sensor calibration
EP2220993B1
( en )
*
2006-04-26
2014-06-18
Nikkiso Co., Ltd.
Biological component-measuring device
US8444609B2
( en )
*
2006-04-28
2013-05-21
Medtronic, Inc.
Implantable therapeutic substance delivery system with catheter access port block and method of use
US8267905B2
( en )
*
2006-05-01
2012-09-18
Neurosystec Corporation
Apparatus and method for delivery of therapeutic and other types of agents
CA2650920C
( en )
2006-05-02
2016-10-18
Proteus Biomedical, Inc.
Patient customized therapeutic regimens
US7941199B2
( en )
2006-05-15
2011-05-10
Masimo Laboratories, Inc.
Sepsis monitor
US8977517B2
( en )
*
2006-06-05
2015-03-10
Creighton University
System and methods for evaluating efficacy of appetite-affecting drugs
ES2751017T3
( en )
*
2006-06-08
2020-03-30
Hoffmann La Roche
System to detect an occlusion in a tube
<tr itemprop="forwardReferencesFamil