Dual stage microvalve and method of use

Surgery – Controlled release therapeutic device or system – Implanted dynamic device or system

Reexamination Certificate

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C604S066000, C600S345000, C600S365000

Reexamination Certificate

active

06663615

ABSTRACT:

TECHNICAL FIELD OF THE INVENTION
This invention relates to micro-machined drug delivery devices and sensors. Specifically, this invention relates to controlled time and rate release multi-staged drug delivery devices and sensors that employ labile drugs, chemicals and molecules.
BACKGROUND OF THE INVENTION
The delivery of drugs is an important aspect of medical treatment. The efficacy of many drugs is directly related to the way in which they are administered. Some therapies require that the drug be repeatedly administered to the patient over a long period of time. This makes the selection of a proper drug delivery method problematic. Patients often forget, are unwilling or are unable to take their medication. Drug delivery also becomes problematic when the drugs are too potent for systemic delivery. Therefore, attempts have been made to design and fabricate a delivery device that is capable of the controlled, pulsatile or continuous release of a wide variety of molecules including, but not limited to, drugs and other therapies.
U.S. Pat. No. 5,797,898 to Santini, Jr. et al. discloses a microchip drug delivery device that consists of a substrate in which at least two reservoirs are formed. Drugs are deposited into the reservoirs. The drugs are kept in the reservoirs by reservoir caps. The drugs are released into the patient by either diffusion through the reservoir cap or by disintegration of the reservoir cap.
The Santini, Jr. et al. device is suitable for delivery of drugs with a lengthy shelf life, however, many drugs are labile. The labile drugs may undergo changes when mixed with pharmaceutical carriers, buffer, or other drugs thus reducing their potency. Additionally, some drugs have such short-lived effective lives that they must be formed almost immediately prior to administration of the drug to the patient. These drugs are not suitable for use in the device taught by Santini, Jr. et al. because the device provides for a singular reservoir. That is to say, the Santini reference does not teach a drug delivery device wherein active components may be separately stored and mixed prior to being released from the delivery device.
Additionally, there is a need for an in vivo biosensing system that can be implanted in a patient and which uses labile sensing reagents. In many cases, desirable sensing reagents are labile and their use results in short-lived sensing systems. A method that would allow for their use over extended periods of time would broaden current in vitro as well as in vivo sensing options considerably. One approach that has been proposed to overcome the problem surrounding the use of labile reagents in in vivo biosensing systems involves the infusion of fresh reagents through an external septum located at the interface of the skin and the subcutaneous tissue [Wilson, G. and Yu. Hu 2000; Bowyer J. R. 1991; Xie, S. L. 1994]. Unfortunately, the drawback of this method is the possible onset of sepsis in the patient's body.
It is therefore an object of the present invention to provide a micro-machined drug delivery device suitable for the delivery of labile drugs, which can operate for weeks or years at a time. It is another object of the present invention to provide a device that allows for the delivery of drugs, molecules or chemicals to a patient in either a pulsitile or continuous manner. It is yet another object of the present invention to provide a device that allows for two or more drugs, chemicals or molecules that have been separately stored in the device to be mixed before being released from the device into the patient. It is yet another object of the present invention to provide a device whose delivery of drugs, chemicals, or molecules to a patient can be controlled either passively or actively. It is also an object of the present invention to provide a device small enough to be implanted in a patient that can hold many different drugs, chemicals, or molecules. It is also an object of the present invention to provide a biosensing device that uses labile reagents and can be implanted into a patient.
SUMMARY OF THE INVENTION
The present invention presents a novel approach for the delivery of a wide variety of drugs by a micro-machined delivery device. The present invention also presents a novel approach for biosensing using labile reagents. Additionally, the present invention presents a novel micro-machined drug delivery and sensor device. Micro-machined devices are constructed using methods commonly applied to the manufacture of integrated circuits such as ultraviolet (UV) photolithography, reactive ion etching, electron beam evaporation, vapor deposition and spin casting.
A micro-machined drug delivery device for the release of molecules of the present invention comprises a substrate with at least one reservoir. Each reservoir has a first stage and a second stage each containing molecules. Further, each reservoir has a reservoir cap positioned on the reservoir over the molecules in the second stage. Each reservoir has a reservoir partition that separates the first stage from the second stage.
A micro-machined biosensing device for the measuring of the concentration of a chemical in the body fluid of a patient of the present invention comprises a substrate with at least one reservoir in the substrate. Each reservoir has a first stage containing a first type of molecules and a second stage containing a second type of molecules. A pair of sensing electrodes is disposed in the second stage of the reservoir. A reservoir cap is positioned on each reservoir over the molecules in the second stage. A reservoir partition separates the first stage from the second stage.
A micro-machined drug delivery and biosensing device, for sensing a concentration of a chemical in a patient and administering drugs of the present invention comprises a substrate in which at least one drug delivery reservoir is disposed and in which at least one sensing reservoir is disposed. Each drug delivery reservoir and each sensing reservoir has a first stage containing molecules and a second stage containing molecules. Each drug delivery reservoir and each sensing reservoir further has a reservoir partition positioned between and separating the first stage and the second stage. Each drug delivery reservoir and each sensing reservoir has a reservoir cap positioned over the molecules in the second stage. The second stage of each sensing reservoir has a pair of sensing electrodes.
A method for releasing molecules in a patient of the present invention comprises inserting a micro-machined drug delivery device in a patient, contacting the molecules in the first stage with molecules in the second stage so as to form a mixture and releasing the mixture from the micro-machined drug delivery system.
A method for sensing a concentration of a chemical in a patient's body fluids of the present invention comprises inserting a micro-machined sensing device into said patient, contacting molecules in the first stage of the micro-machined device with molecules in the second stage so as to form a sensing element by disintegrating a reservoir partition thereby combining the first stage and second stage to form a volume, permitting body fluid to enter the volume where the body fluid reacts with the recently formed sensing element to produce a signal detected by sensing electrodes, and sending said detected signal to control circuitry.
A method for sensing a concentration of a chemical in a patient's body fluids and releasing drugs into the patient's body of the present invention comprises inserting a micro-machined drug delivery and sensing device into the patient, contacting said molecules in said first stage of said sensing reservoir with said molecules in said second stage of said sensing reservoir so as to form a sensing element by disintegrating said reservoir partition, said first stage and said second stage of said sensing reservoir combining to form a volume; permitting body fluid to enter said volume where said body fluid reacts with said sensing element to produce a sign

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