Patent Application
20090137926
Generally the present invention relates to the field of drug delivery. More particularly, the present invention provides a device and methods for sustained transdermal drug delivery using repetitive microjets.
Traditionally, the dominant method of delivering medication into the human body has been by oral ingestion of pills. Once ingested, the medication is theoretically absorbed across the gastrointestinal (GI) tract and into the blood stream for systemic delivery. However, a large fraction of drug candidates, which may be highly promising drugs, either do not have the right solubility to be absorbed by the GI tract or are destroyed by digestive secretions prior to being absorbed. Of the drugs that are absorbed by the GI tract, a large fraction of these are metabolized by the liver and rendered inactive before their full beneficial effect can be appreciated. Furthermore, today's pharmaceutical industry is shifting toward higher molecular weight biopharmaceutical type drugs. Along with this shift will come an increase in the number of drugs that cannot effectively be delivered orally.
Another method of drug delivery is transdermal drug delivery. Transdermal drug delivery is the delivery of the drug substance directly across the skin barrier. Transdermal drug delivery has been in existence for roughly two decades. Transdermal delivery has many advantages over other drug delivery methods, including avoiding first pass metabolism and the ability to maintain consistent systemic dosage levels avoiding the peaks and troughs experienced with pills, injections, pulmonary, and transmucosal drug delivery methods. Furthermore, transdermal drug delivery is an extremely convenient dosage vehicle for the patient and tends to achieves high levels of patient compliance.
While applications proving appropriate for transdermal delivery are highly effective, few drug candidates actually materialize as candidates for transdermal delivery. Traditional transdermal drug delivery relies on the drug permeating the skin. In use, only a small number of drugs are actually passively absorbed through the skin at therapeutic levels. Currently, there are approximately only ten drugs that are commercially available in transdermal formats. Moreover, today's macromolecule drugs, have a much larger mass than the typical successful transdermal drug and have limited solubility in lipid bilayers and, therefore, will have even more limited transdermal applications.
The main barrier to diffusion of pharmaceuticals across the skin is the outermost layer of the skin, the stratum corneum. The stratum corneum consists of densely packed keratinocytes (flat dead cells filled with keratin fibers) surrounded by highly ordered lipid bilayers, creating an effective barrier to permeability. Directly beneath the stratum corneum is the epidermis. The epidermis is rich in cells of the immune system, and therefore a target for drug delivery for therapies that are directed to or involve the immune system. Beneath the epidermis is the dermis. The dermis has a rich network of blood capillaries and, therefore, is an attractive target for systemic drug delivery since drugs presented to the capillary network rapidly enter the circulatory system and are systemically delivered throughout the body.
Various methods for enhancing transdermal drug delivery across the stratum corneum have been devised including utilizing enhancing agents or stimulants such as chemical, voltage charge, ultrasonic waves, thermal treatments, microneedles, and laser assist techniques. For example, see U.S. Pat. Nos. 6,352,506 and 6,216,033. However, the development and broad acceptance of these methods has been hampered by skin irritation, incompatibility with the drug formulations, and the complexity and expense of the devices themselves. Furthermore, these techniques do not offer the capability of time-dependent dosage delivery, which is crucial to many therapeutics, including insulin.
Another mechanism of drug delivery is the use of needless injections or high-speed jet injectors. High-speed jet injectors have been utilized as hypodermic syringe replacements for many years. For example, see U.S. Pat. Nos. 2,380,534; 4,596,556; 5,520,639; 5,630,796 and 5,993,412. Jet injectors move the solution to be injected at a high rate of speed and eject the solution as a jet, penetrating the stratum corneum and depositing the solution into the dermis and subcutaneous regions of the skin.
While traditional high-speed jets are capable of transporting drugs across the stratum corneum, a drawback of this mechanism is that they deliver a large quantity of the composition being delivered in a one-time jet injection. As a result, some of the drug is often forced back out of the penetration pore from the pressure that is developed by the large quantity of the delivery. Moreover, the one-time delivery fails to maintain a sustained systemic drug concentration at therapeutic levels. Still further, due to the large quantity of drug delivered at one-time, patients often experience skin irritation, pain, swelling, and other undesirable effects similar to injections with hypodermic syringes.
Therefore, less-invasive techniques for sustained transdermal delivery of a composition at consistent therapeutic levels to a patient would be highly desirable.
The present invention provides an active, fluid delivery system that generally includes a support structure with at least one exit orifice. The exit orifice has a diameter of between about 1 μm and about 500 μm. The fluid delivery system also has a fluid reservoir configured to contain a fluid to be delivered to a tissue. The fluid reservoir is configured and dimensioned to communicate with the exit orifice. A repeatable activation means cooperates with the fluid reservoir and the exit orifice for ejecting fluid in response to an activation signal.
In an alternative embodiment, the fluid reservoir and the repeatable activation means are disposed in the support structure. The support structure can be adapted to be in contact with a skin surface with the exit orifice adjacent the skin surface. The support structure can also include a nozzle defining the orifice. The nozzle is configured and dimensioned to accelerate the fluid exiting therefrom.
According to another embodiment of the present invention, the fluid delivery system includes a controller in communication with the repeatable activation means. The controller is designed to be capable of generating the activation signal. The controller can be a microprocessor that is programmable to control a patterned administration regime to be delivered from the fluid delivery system. The patterned administration regime preferably occurs over a time period of not less than about 500 ms and not more than about 10 days.
The nozzle of the fluid delivery system can be configured to maintain the fluid remote from the tissue a substantially fixed distance prior to ejection of the fluid from the nozzle. The fixed distance preferably spaces the fluid, prior to ejection of the fluid, not more than about 5000 μm from the tissue.
According to yet another embodiment, the fluid delivery system includes an array of exit orifices defined in the support structure and in communication with the fluid reservoir. The fluid reservoir can include a storage reservoir configured to store fluid. The fluid reservoir can also include a pressurization mechanism for pressurizing the stored fluid in the storage reservoir. Furthermore, the storage reservoir can be divided into at least two storage reservoirs by a reservoir divider.
According to an embodiment, there are at least two exit orifices defined in the support structure. A first exit orifice is in communication with a first storage reservoir storing a first fluid such that the first fluid can be ejected through the first exit orifice. There is also a at least a second exit orifice in communication with at least a second storage reservoir storing a second fluid such that the second fluid can be ejected through the second exit orifice.
According to an alternative embodiment, the reservoir divider can include a reservoir divider disruption mechanism configured and dimensioned to disrupt the reservoir divider prior to administration of a substance contained in the reservoir. The reservoir divider disruption mechanism can be a piezoelectric mechanism, for example.
In another embodiment, the fluid delivery system includes a sensor for sensing if a condition is satisfied. Also included is a control unit configured to produce the activation signal to actuate the repeatable activation means upon receiving a signal from the sensor that the condition is or is not satisfied. The sensor can be located remotely from the support structure, implanted into the patient, located within the support structure, or the like. Furthermore, the sensor is capable of sensing a biological condition of a patient, such as temperature, pressure, chemical or molecular concentration, or the like.
In yet another alternative embodiment, the fluid delivery device includes an antagonist reservoir configured and dimensioned in cooperation with the fluid reservoir such that, upon compromise of the integrity of both reservoirs, the antagonist reservoir releases an antagonist agent which can inactivate the fluid.
In a preferred embodiment, the fluid delivery system also includes a power supply for supplying a drive force for the activation signal and a drive force for the repeatable activation means.
According to an embodiment, the repeatable activation means is a piezoelectric mechanism that generates a pressure change in the fluid. According to another embodiment, the repeatable activation means is a phase change mechanism that generates a pressure change in the fluid. In yet another embodiment, the repeatable activation means is an electromagnetic mechanism that generates a pressure change in the fluid. In still another embodiment, the repeatable activation means is a high pressure hydraulic mechanism that generates a pressure change in the fluid. According to yet another embodiment, the repeatable activation means includes multiple explosive mechanisms, each explosive mechanism capable of generating a pressure change in the fluid upon detonation of said explosive mechanism.
According to a preferred embodiment, the repeatable activation means generates a pulse width of not less than about 5 ns and not more than about 10 μs in duration. The frequency of the repeatable activation means and a duty cycle and length of ejection of fluid are controlled by a control unit.
In a preferred embodiment, the system further includes a user interface in communication with the repeatable activation means. The user interface being configured to initiate the activation signal in response to manipulation of the user interface.
In use of an embodiment of the fluid delivery system, the fluid is to be delivered transdermally across epithelial tissue.
The fluid delivery system preferably includes a memory for storing a delivery profile and delivery history of the fluid delivered to the tissue.
In an alternative embodiment of the present invention, the fluid includes an analyte for delivery to the tissue and subsequent diagnoses of a biological condition.
According to an embodiment of the present invention including a phase change mechanism, the system further includes a flexible membrane dividing the fluid reservoir into a first compartment and a second compartment, wherein the first compartment contains an actuation fluid in communication with said phase change mechanism and the second compartment contains the fluid to be delivered. In yet another embodiment, the actuation fluid is positioned near the phase change mechanism and the actuation fluid is immiscible with the fluid to be delivered.
According to an embodiment of the present invention, the fluid ejection chamber, at least one exit orifice, and activation means are configured and dimensioned together for continuously cyclic repeatable ejection of fluid in the range of about 1 pl to about 800 nl.
For a better understanding of the nature and objects of the invention, reference should be made to the following detailed description, read in conjunction with the accompanying drawings, in which:
Reference will now be made in detail to the preferred embodiments of the invention, examples of which are illustrated in the accompanying drawings. While the invention will be described in conjunction with the preferred embodiments, it will be understood that they are not intended to limit the invention to those embodiments. On the contrary, the invention is intended to cover alternatives, modifications, and equivalents, which may be included within the spirit and scope of the invention as defined by the appended claims.
Referring now to a repetitive microjet device 100 as shown in
Furthermore, the repetitive microjet device 100 is capable of repeatable activation. For the sake of clarity, repeatable activation is defined to mean multiple, sequential activation without the need to remove, recharge, or otherwise replenish the device between activation cycles and deactivation cycles. For example, a particular drug administration regime may be to deliver a particular quantity of the drug on each hour for five days. In this example, the repetitive microjet device would activate the force generation mechanism, described below, repetitively, to inject as many micro injections as needed to deliver the prescribed quantity of drug at the first hour. Upon completion of a first hours administration, the device would wait until the next hour, then administer the prescribed quantity of drug a second time. The device would then continue in this manner for the entire five day period. Moreover, according to an embodiment, microprocessor 106 is a simple electronic component or control unit that generates a signal according to predetermined or preprogrammed timing. The timing of the signal can be sequential, but is not limited to sequential timing. The signal then generated by the control unit activates the microjet to propel a jet of fluid toward the biological barrier.
According to another embodiment, as shown in
For simplicity and clarity the following description will primarily describe in detail the components of the single transdermal microjet device 100, as shown in
Transdermal microjet device 100 includes a housing 128. Housing 128 can be constructed from a plastic, metal, ceramic, or other suitably bio-compatible material. Preferably, housing 128 is constructed from a polymer based material such that transdermal microjet device 100 is semi-flexible, can conform to the contour of a surface to which it is applied, is biocompatible, and is drug inert. For example, if transdermal microjet device 100 is configured as a drug delivery patch, it would be advantageous that housing 128 can flex to conform to the contour of the human body at the position at which it is applied. Furthermore, it would be advantageous for transdermal microjet device 100 to be disposable and have a low manufacturing cost. However, it is perceived that it may be advantageous to construct transdermal microjet device 100 from a material not a polymer such that, for example, transdermal microjet device 100 can be sterilized and reused. It may be further preferable to construct transdermal microjet device 100 such that the components are not contained within a single housing. According to such an embodiment, the microprocessor may be separate from the reservoir, which can both be separate from the delivery portion configured to interface with a biological tissue. In such an embodiment, the components; microprocessor, reservoir, and delivery portion are in fluid, electrical, or both communication with each other.
Reservoir 102, as shown in
According to a preferred embodiment, reservoir 102 can be pressurized such that injectate 108 contained within is urged out of reservoir 102. Alternatively, injectate 108 can be actively pumped out of reservoir 102 by a pump 132.
According to an embodiment, as shown in
In yet another embodiment, as shown in
In a preferred embodiment, reservoir 102 can be divided into more than one internal chambers as shown in
According to a preferred embodiment, reservoir 102 has a volume that is not less than about 100 μl and not greater than about 500 ml. In an alternative embodiment, it is preferred that the volume of reservoir 102 is not less than about 150 μl and not greater than about 1 ml. In yet another embodiment, it is preferred that the volume of reservoir 102 is not less than about 200 μl and not greater than about 750 μl.
Reservoir divider 320 is configured to be ruptured my a rupture mechanism 322 prior to administration such that the compositions housed with the divided reservoir can mix in preparation for administration. Preferrably reservoir divider 320 is constructed from biocompatible polymeric foils such as polyethylene, polystyrene, polyethyleneterephthalate (PET), and elastomeric polymers such as polydimethylsiloxane (PDMS), however, it will be appreciated by one of ordinary skill in that art that any thin, non-permeable, drug inert membrane is a candidate for dividing the reservoir into multiple compartments.
Rupture mechanism 322 can be, for example, a ball placed in one of the reservoir chambers. In use, upon shaking or manipulation of the repetitive microjet device 100, the ball moves separately from the device and impacts reservoir divider 320, thereby rupturing reservoir divider 320 and allowing mixing of the different compositions housed in the reservoir chambers 324 and 326. Along with rupturing reservoir divider 320, the ball can facilitate mixing of the drug compositions, thereby, ensuring proper mixing of the injectate prior to administration.
According to an alternative embodiment, rupture mechanism 320 can be a mechanism that is controlled by microprocessor 106. This rupture mechanism 320 can be, for example, a piezoelectric mechanism. According to such an embodiment, the microprocessor 106 controls the delivery of a supply of voltage, from the power supply to the piezoelectric rupture mechanism. The piezoelectric rupture mechanism creates mechanical pressure waves such as ultrasound waves in the fluid media upon application of an alternating current. These mechanical pressure waves serve to rupture the reservoir divider.
According to such an embodiment, the reservoir can be divided into multiple reservoirs. Microprocessor 106 can control the timing and sequence of rupture of reservoir dividers 320 such that particular reservoir dividers can be ruptured, thereby releasing compositions for mixing. In this manner, only the portion of compositions that will be currently administered, i.e., a current dosage, is mixed and the remaining quantity of composition remains in stable discrete form in discrete reservoirs. As a result, repetitive microjet device 100 can discretely house treatment compounds, which can remain viable for long periods of time for repetitive delivery of treatments over sustained periods.
Microprocessor controlled rupture mechanism 320 can be, for example, an electrical impulse generated by microprocessor 106. Each independent reservoir divider 320 can include electrodes that, when activated, cause the respective reservoir divider to rupture, thereby allowing subsequent mixing of compositions for administration. Alternatively, rupture mechanism 320 can be, for example, physical disruption of reservoir divider 320 such as by spearing, twisting, shock-wave, explosion, or the like. Rupture mechanism may be any such mechanism that is capable of rupturing or disrupting the integrity of the non-permeable reservoir dividers.
Often in medical applications the treatment of patients requires drugs which may be illicit outside of the prescription care of a physician. Some of these drugs may be addictive and eagerly sought by individuals for use outside of the prescribed use. Because transdermal microjet device 100 includes reservoir 102 that may store a quantity of such drug components for repetitive and sustained administration, it is conceivable that some individuals may seek to extract the drug components from reservoir 102 for illicit uses. Therefore, it can be advantageous to include an antagonist reservoir 350 in transdermal microjet device 100, as shown in
Antagonist reservoir 350 is designed to be easily disrupted, releasing antagonist 352 from within when the transdermal microjet device 100 is manipulated or tampered with in a manner sufficient to extract injectate 108 from reservoir 102. When antagonist reservoir 350 is disrupted the antagonist 352 will be released, such that the injectate 108 drug components will be inactivated.
Antagonist reservoir 350 can be, for example, a reservoir that is positioned to surround reservoir 102 and constructed from a material which will be disrupted more easily than reservoir 102. Alternatively, as shown in
In yet another embodiment, as shown in
Referring back to
Feed line 110 can include a valve 112. Valve 112 is preferably a one-way valve such that flow of injectate 108 is restricted to flowing in the direction toward microjet 104, and restricted from flowing in the reverse direction, toward reservoir 102. Feed line 110 extends to and is fluidly coupled with nozzle 114 of microjet 104.
In a preferred embodiment, feed line 110 contains a pressure regulator 116 to regulate the pressure in feed line 110. Injectate 108 can be maintained under pressure in reservoir 102, as described above, to a higher pressure than the desired pressure in nozzle 114. Therefore, pressure regulator 116 functions to regulate downstream pressure in feed line 110 such that the pressure of injectate 108 at nozzle 114 is maintained at an appropriate level. The appropriate level will be appreciated by one of ordinary skill in the art to be a pressure that fills nozzle 114 with injectate 108 but does not overcome the forces that maintain injectate 108 within nozzle 114, as described in more detail with respect to the description of nozzle 114 herein.
Microjet 104,
Force generation mechanism 118,
According to an embodiment, force generation mechanism 118 is a piezoelectric mechanism 400, as shown in
Microprocessor 106, described in more detail below, is connected to piezoelectric mechanism 400 through circuitry 124,
According to the embodiment shown in
According to an embodiment having an array of piezoelectric microjets 420,
According to an alternative embodiment, the force generation mechanism can be a phase change mechanism 430, as shown in
Actuation fluid 436 is a fluid that is easily broken down and vaporizes rapidly upon the build-up of a difference in electric charge on electrodes 432 and 434. The actuation fluid 436 is typically a conductive ionic fluid including but not limited to a saline fluid, other salt solutions in water such as aqueous metal halides, i.e., potassium chloride, calcium chloride, and the like, can also be utilized. Furthermore, dielectric materials with low boiling points can also be utilized as actuation fluid 436, such as fluorocarbons.
According to an alternative embodiment, the actuation fluid 436 can be the injectate. Accordingly, the flexible membrane 438 may not be necessary as the entire chamber 120 and nozzle 114 are filled with the fluid that is ultimately injected following activation of the phase change mechanism.
Because the volume of a given amount of fluid increases vastly when the fluid is changed into its gaseous form, generating a vaporization of a given amount of fluid in a fixed volume chamber will vastly increases the pressure with the chamber. Thereafter, the flexible membrane 438 is deformed in the proximal direction, thereby decreasing the volume of nozzle 114. As a result, the injectate 108 is forced in the proximal direction and becomes ejected from nozzle 114, as described in more detail below.
Microprocessor 106 is in electrical communication with phase change mechanism 430 through circuitry 124. Similar to activation of the piezoelectric mechanism, as described above, microprocessor 106 can control the actuation of phase change mechanism 430. Following vaporization of actuation fluid 436, the actuation fluid 436 reforms as fluid and is capable of a repetitive vaporization, thereby, generating a repetitive microjet. In an embodiment employing an array of microjets 204,
In an alternative embodiment, actuation fluid 436,
According to another embodiment, as shown in
The phase change mechanism of the present invention generally operates on a high voltage of not less than about 500V and not more than about 10 kV. The phase change mechanism preferably operates on a voltage of not less than about 1 kV and not more than about 6 kV. In an alternative embodiment, the phase change mechanism of the present invention operates on a voltage of not less than about 3 kV and not more than about 6 kV. The voltage is pulsed at not less than about 5 ns and not more than about lops. In an alternative embodiment the voltage is pulsed at not less than about 0.5 μs and not more than about 5 μs. In yet another alternative embodiment, the voltage is pulsed at not less than about 1 μs and not more than about 3 μs.
The flexible membranes 438 and 460 are preferably constructed from a low Young's modulus elastomer material, such as polydimethylsiloxane (silicone rubber), fluoropolymer (Kalrez), or the like. The preferably thickness of flexible membranes 438 and 460 are not less than about 0.1 μm and not more than about 100 μm. In an alternative embodiment, the flexible membranes 438 and 460 are not less than about 0.5 μm and not more than about 50 μm in thickness. According to yet another embodiment, the flexible membranes 438 and 460 are not less than about 1 μm and not more than about 10 μm in thickness.
According to yet another embodiment, force generation mechanism 118, (
According to yet another embodiment, force generation mechanism 118 (
In still a further embodiment of the present invention, force generation mechanism 118 (
In still a further embodiment, the force generation mechanism 118 can be an explosive mechanism. The explosive mechanism can include, for example, a mixture of chemicals that upon the delivery of a voltage or other type of ignition source, excite and produce an explosion. The explosion thereafter generates a pressure change within chamber 120 and drives injectate from nozzle 114 and into the adjacent biological tissue.
Chamber 120,
Referring to
As described above, an embodiment of the present invention utilizes a feed line 110 maintaining reservoir 102 and nozzle 114 in fluid communication. Also, as described above, reservoir 102 can be pressurized or include a pump 132, such that injectate 108 is urged down feed line 110 and into nozzle 114, thus refilling nozzle 114 and chamber 120 following each ejection of injectate 108. Alternatively, feed line 110 can be coupled with and empty into chamber 120 rather than nozzle 114.
In a preferred embodiment, the diameter of the opening of feed line 110 at the intersection of chamber 120 and/or nozzle 114 is substantially smaller than the opening of nozzle 114 such that flow of injectate 108 into feed line 110 in the reverse direction is negligible. Also, there can be a deflector plate 134,
According to an alternative embodiment, injectate 108 refills nozzle 114 and chamber 120 by capillary action if reservoir 102 is not pressurized.
In an alternative embodiment,
According to yet another embodiment, as shown in
According to the nozzle of
According to an embodiment, as shown in
Alternatively, the proximal end of nozzle 114 can have a convergent/divergent configuration 606, as shown in
According to an embodiment of the present invention, as shown in
According to an alternative embodiment, as shown in
Nozzle 114 preferably has an orifice diameter of not less than about 1 μm and not greater than about 500 μm. According to another embodiment, nozzle 114 has an orifice diameter not less than about 25 μm and not greater than about 250 μm. More preferably, nozzle 114 has an orifice diameter not less than about 30 μm and not greater than about 75 μm.
Nozzle 114 can be manufactured by many known methods in the art, for example, one method includes heating a glass tube and pulling the tube to obtain a desired diameter then scribing, braking, and polishing the tube to perfect the nozzle. Another more preferable method includes molding the nozzle or injection molding the nozzle from a master mold. Still another method of manufacturing the nozzle includes using photolithographic processing and etching. Another method of manufacturing the nozzle includes, for example, laser drilling. These methods are well known in the art and will be appreciated by one of ordinary skill in the art, therefore, further explanation is not necessary. Moreover, it will be appreciated by one of ordinary skill in the art that nozzle 114 can be tapered, conical, straight, of complex shape, or the like.
According to another embodiment, wherein the device is configured with an array of microjets 204 and an array of nozzles 214, as shown in
According to yet another embodiment with an array of microjets 204,
A preferred microprocessor 106 will now be described. As shown in
Microprocessor 106 can be programmed to control the activation of the microjet to deliver a certain dosage of treatment to a patient at specified intervals over a specified time period. At the appropriate time, microprocessor 106 will initiate actuation of microjets 104 to fire or actuate and deliver the prescribed treatment(s). Therefore, a patient can benefit from a system that maintains optimal dosage levels in the systemic system throughout the day and night automatically (without further human intervention), such that the treatment may have an optimal effect on the patients condition. Moreover, because delivery or injection with the jet of injectate only penetrates the stratum corneum and delivers the treatment into the epidermis, where there is no nerve endings, the process is painless to the user. Microprocessor 106 can also control the destruction of reservoir dividers 320,
According to another embodiment, memory 702 of microprocessor 106 maintains a record of the quantity of injectate delivered, timing of administration, number of administrations, and the like for future analysis and evaluation to improve the treatment regime for patients.
In an alternative embodiment, microprocessor 106, can also include a user interface 704. User interface device 704 can be a button, switch, or other mechanism which can be activated by the user to stimulate an administration of injectate at any given time. For example, a boost button 136 can be positioned such that it is in communication with microprocessor 106 through a booster button communication link 138. Accordingly, if a patient or administrator determines a need to deliver a treatment dosage of injectate at any given time the boost button 136 can be activated, thereby bypassing the programmed administration regime and delivering an on-demand predetermined dosage of injectate. This can be advantageous for an embodiment where the device is used to deliver pain medication because the need for pain medication can arise outside of a predetermined delivery regime. However, associated with user interface device 704, microprocessor 106 can be pre-programmed with a safety feature such that the user can only trigger the user interface device 704 as many times in a given period, such that, a patient will not overdose or abuse an injectate. The number of times a patient can activate the user interface device 704 can be adjustable depending on what substance comprises the injectate, the age of the patient, the weight of the patient, the severity of the condition of the patient, or the like.
According to yet a further embodiment, microprocessor 106 has communications interface circuitry 706 to communicate with another computer system. A doctor, researcher, or the like can interface with microprocessor 106 through a computer, handheld computer, wireless connection, or the like and access information regarding the frequency of administration, dosage delivered at each interval, variety in dosage delivered, total dosage delivered, and the like. Furthermore, the doctor or researcher can download data 718 saved in memory 702 or modify the administration regime or activation procedures 716. Interfacing with microprocessor 106 can be useful to the continued understanding of treating certain conditions and the development of new and better treatment substances and regimes.
In an alternative embodiment, as shown in
According to another embodiment, the device 100 can include a condition sensor 133,
Microprocessor 106,
Referring back to
According to an alternative embodiment, as shown in
Alternatively, transdermal microjet device 800, as shown in
According to a preferred embodiment of the present invention the transdermal microjet device is configured as a drug delivery patch 900, as shown, for example, in
The microjet layer 902, control circuitry layer 904, and reservoir layer 906 typically comprise the administration unit which is preferably disposable following complete administration of the drug components. While a microprocessor 908 is housed in a microprocessor layer which is not necessarily disposable and adapted to interact with the administration unit such that a patient can retain the microprocessor layer 908 and re-connect it to a new administration patch. As shown in
Reservoir layer 906 preferably includes a recessed area 910 which, when coupled with control circuitry layer 904 forms a reservoir for storing injectate components. Reservoir layer 906 is fluidly coupled with microjet layer 902 through feed line 912 for maintaining microjets 914 supplied with injectate. Control circuitry layer 904 includes the electrical circuitry 916 that activates microjets 914. Surface A, the proximal surface of microjet layer 902 preferably includes an adhesive for adhering transdermal drug delivery patch 900 to the skin of a user.
Microprocessor layer 908 typically includes microprocessor 106 and can include power supply 122. Microprocessor layer 908 is configured to house the microprocessor 106 for controlling the actuation of microjets 914. Microprocessor layer 908 is electrically coupled with control circuitry layer 904 through control line 918. Preferably, microprocessor layer 908 is configured to be removably attachable to the administration patch such that microprocessor 106 can be retained after the injectate 108 of administration patch is completely expelled or administration of a particular injectate is complete. Accordingly, a patient can then receive a renewed administration patch with further injectate to be administered and microprocessor 908 can be affixed thereto such that administration of the injectate can continue as earlier programmed for the particular patient or treatment regime.
The power supply 122 may be housed in the administration patch or in the microprocessor layer 908. When the power supply is housed in the administration patch, it is configured to be disposed of with the administration patch following completion of treatment. Therefore, in this configuration, each time the user receives a new administration patch, a new power supply will be provided, assuring that the power supply will not fail partially through a treatment regime.
In an alternative embodiment, as shown in
Preferably the laminate layers are bound together. The laminate layers can be bound together with a chemical bond, thermal bond, or the like. Furthermore, it is desirable that the patch be constructed in an efficient economical form and be disposable following administration of the contents.
Laminate layers 902, 904, and 906 are preferably constructed from a flexible, biocompatible, drug inert material such that drug delivery patch 900 can be applied to a position on a human body and conform to the contour of the body. Furthermore, because transdermal drug delivery patch 900 is flexible it does not restrict activity of the user. According to an alternative embodiment, transdermal drug delivery patch 900 can be constructed from material that is not flexible. Therefore, the transdermal drug delivery patch 900 does not contour to the position of application.
The transdermal microjet device 100 can be configured as a transdermal drug delivery system that is applied to the skin of the user by an adhesive. In alternative embodiments, the device can be positioned in contact with the skin, affixed in place by belt, a buckle, adjustable bands such as elastic bands, or the like.
According to an alternative embodiment, transdermal microjet device 100 can be configured as a hand held or robot held applicator of drugs, treatment solutions, saline solutions, or the like for treating a biological disorder, injury, disease, condition, or the like. Alternatively, the transdermal microjet device can be configured as an implantable device that interfaces with internal organs, tumors, biological barriers such as the dura mater and pia mater, or the like. Furthermore, the transdermal microjet device can be configured as a long term implantable sustained controlled drug release mechanism. The implantable mechanism can be controlled wirelessly from external to the implant site for altering the programmed treatment regime. The device, as described above, can also be utilized in place of an intravenous drug delivery system. In this embodiment, the device can be used to deliver the drug transdermally into the epidermis. The device can be placed on the patient's skin and the device reservoir can be a traditional intravenous (IV) drug drip supply, for example. The drug diffuses from the epidermis into the vein in a very short period of time that can be tolerated in a large number of IV drug delivery application. Furthermore, in patients needing sustained intravenous treatments, complications often arise in relation to the implant site of the catheter. Also, the site of catheter insertion is a prime route for infection to enter the body. The use of the present invention according to this embodiment reduces the chance for infection and other complications from the traditional intravenous drug delivery systems.
Because the present invention is directed to a mechanism and methods for mechanical delivery of drugs to a biological tissue the mechanism is applicable to drugs irrespective of their physicochemical properties such as partition coefficient, solubility, charge, molecular weight, and the like. However, it will be appreciated by one of ordinary skill in the art that a substance can be added to the injectate to increase permeability of the skin. Such a substance can be a chemical surfactant or the like.
During administration of the injectate to the biological tissue, data relating to the administration of the injectate is recorded, at step 1014. Data that may typically be recorded includes the time of each administration, the quantity of each administration, and the like. In an alternative embodiment, the device may include sensors, such as biosensors that monitor and record biological activity of the patient, such as temperature, blood pressure, pulse, blood glucose levels, or other such biological and/or chemical conditions of the patient. Next, if the physician or researcher in charge of the biological tissue being treated wishes, they can electronically interface with the device and receive the data that is being recorded in real time and/or at any time during administration of the injectate, as shown at step 1016. The physician or researcher can also change the administration regime through the electronic interface with microprocessor 106 during the administration period of the injectate, at step 1018. Next, the administration of the injectate is allowed to carry out the administration regime, at step 1020.
If, following the complete administration of an injectate, the condition is alleviated, then the method terminates at step 1024. However, if following complete administration of an injectate, the condition is not alleviated, then the microprocessor 106 is disconnected from the administration unit, the administration unit is discarded, and the microprocessor is retained, at step 1026. A new injectate is prepared, at step 1004, and the treatment method continues as previously described. The new injectate can be another quantity of the same injectate previously administered or a different injectate composition can be administered.
An exemplary description of the performance of the steps of
This application is a divisional of application Ser. No. 10/829,888, filed Apr. 21, 2004, which claims priority to provisional applications Nos. 60/463,905, filed Apr. 21, 2003; 60/483,604, filed Jun. 30, 2003; and 60/492,342 filed Aug. 5, 2003. All these priority documents are incorporated herein by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 60463905 | Apr 2003 | US | |
| 60483604 | Jun 2003 | US | |
| 60492342 | Aug 2003 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10829888 | Apr 2004 | US |
| Child | 12366091 | US |
