Abstract:
An injector includes a housing having a chamber for holding a liquid formulation of an active principle to be injected into a biological body and an output port in fluid communication with the chamber through which the liquid formulation is injected. A piston is positioned within the housing, and includes an end portion with substantially the same shape as the chamber. A magnetic force draws the piston and housing together to expel the liquid formulation out of the chamber through the output port.

Description:
RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 10/200,574 filed Jul. 19, 2002, now U.S. patent No. 6,939,323, which claims the benefit of U.S. Provisional Application No. 60/338,169, filed Oct. 26, 2001, the entire teachings of which are incorporated herein by reference. 
    
    
     BACKGROUND 
     Injection of a liquid such as a drug into a human patient or an agriculture animal is performed in a number of ways. One of the easiest methods for drug delivery is through the skin which is the outermost protective layer of the body. It is composed of the epidermis, including the stratum corneum, the stratum granulosum, the stratum spinosum, and the stratum basale, and the dermis, containing, among other things, the capillary layer. The stratum corneum is a tough, scaly layer made of dead cell tissue. It extends around 10-20 microns from the skin surface and has no blood supply. Because of the density of this layer of cells, moving compounds across the skin, either into or out of the body, can be very difficult. 
     The current technology for delivering local pharmaceuticals through the skin includes methods that use needles or other skin piercing devices. Invasive procedures, such as use of needles or lances, effectively overcome the barrier function of the stratum corneum. However, these methods suffer from several major disadvantages: local skin damage, bleeding, and risk of infection at the injection site, and creation of contaminated needles or lances that must be disposed of. Further, when these devices are used to inject drugs in agriculture animals, the needles break off from time to time and remain embedded in the animal. 
     Thus, it would be advantageous to be able to inject small, precise volumes of pharmaceuticals quickly through the skin without the potential of a needle breaking off in the animal. 
     SUMMARY 
     Some have proposed using needleless devices to effectively deliver drugs to a biological body. For example, in some of these proposed devices, pressurized gas is used to expel a drug from a chamber into the body. In another device, a cocked spring is released which then imparts a force on a chamber to expel the drug. In these types of devices, however, the pressure applied to the drug decreases as the gas expands or the spring extends. It is desirable, however, for the injection pressure to remain the same or increase during the injection period. 
     In one aspect of the invention, an injector includes a housing having a chamber for holding a liquid formulation of an active principle to be injected into a biological body and an output port in fluid communication with the chamber through which the liquid formulation is injected. A piston is positioned within the housing, and includes an end portion with substantially the same shape as the chamber. A magnetic force draws the piston and housing together to expel the liquid formulation out of the chamber through the output port. 
     Embodiments of this aspect can include one or more of the following features. The output port can have a diameter of approximately 50 μm to 200 μm, and the chamber can have a tapered shape. The injector includes an inlet port for filling the chamber with the liquid formulation. The injector includes an actuator attached to the piston and is made of shape memory alloy. The actuator moves the piston away from the housing when a potential is applied to the actuator. When the potential is removed the piston moves towards the housing. The actuator is a fiber of the shape memory alloy, and the shape memory alloy can be Ni—Ti. The shape memory alloy is approximately 10 mm to 200 mm long, and it contracts approximately 0.5 mm to 10 mm when the potential is applied to the alloy. The shape memory alloy structure changes phase from martensite to austenite when the potential is applied to the alloy. 
     In some embodiments, the injector includes a capacitor that applies the potential when it discharges. The capacitor has an energy output of at least 10 J and can be approximately 100 J. 
     The injector has an injection pressure of at least 1 MPa and a maximum injection pressure of approximately 300 MPa. In certain embodiments, the injector has a cycle time of about one sec. 
     In another aspect of the invention, an actuator includes a contracting material under tension produced by a magnetic force, and a capacitor which is able to discharge a potential to the fiber to cause the fiber to contract. The fiber relaxes to a stretched state when the potential is removed. The contracting material can be a shape memory alloy or a contracting polymer or polymers, or any other suitable contracting material. 
     In yet another aspect of the invention, a injector includes a housing having a chamber for holding a liquid formulation of an active principle to be injected into a biological body, and an output port in fluid communication with the chamber through which the liquid formulation is injected. A piston is positioned within the housing, and includes an end portion with substantially the same shape as the chamber. An actuator is attached to the piston and made of shape memory alloy. The piston and housing are drawn together by a magnetic force, and the actuator moves the piston away from the housing when a potential is applied to the actuator, and the piston moves towards the housing when the voltage is removed to expel the liquid formulation out of the chamber through the output port. 
     Related aspects of the invention include a method of injecting a liquid formulation of an active principle into a biological body with an injector having one or more of the aforementioned features, and a method of actuating a fiber of shape memory alloy. 
     Embodiments of this invention can have one or more of the following advantages. The injector is self-contained and portable. Since the injection process is needleless, there are no needles that can break off and remain within the biological body. Since the injector can be re-charged at a rapid rate, a large number of animals can be injected with the liquid formulation over a short period of time. Further, since the injector contains enough liquid formulation for numerous injections, the operator is able to inject many animals with a single injector before refilling a reservoir or a set of reservoirs or obtaining another injector with a filled reservoir. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. 
         FIG. 1  is a side schematic view of a drug delivery device in accordance with the invention. 
         FIG. 2A  is a graph of the time response of a shape memory alloy actuator of the drug delivery device of  FIG. 1  for a high strain. 
         FIG. 2B  is a graph of the time response of the shape memory alloy actuator when the actuator is subjected to a potential as a quick pulse. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     A description of preferred embodiments of the invention follows. 
     Referring to  FIG. 1 , there is shown a schematic view of a drug delivery device  10  which is used to inject a liquid formulation of an active principle such as, for example, a drug into a biological body such as a agriculture animal. The drug is initially contained in a chamber  12  of the device and is injected out through an orifice  13  into the animal. A drug reservoir  14  supplies the chamber  12  with sufficient amount of the drug for each injection and holds enough of the drug for approximately 20 to 200 or more injections. Alternatively, and particularly for use with humans, individual doses may be provided in a plurality of reservoirs sequentially coupled to the delivery device. 
     The device  10  includes a horn  18  in which a piston  20  is positioned. One end of an actuator  22  is attached to the piston  20 , and the other end is attached to a surface  24 . The surface  24  and the horn  18  are mounted in a manner, for example, within an applicator, such that the piston  20  is able to move back and forth in the direction of the double arrow A relative to the horn  18  and the surface  24 . 
     The horn  18  includes an outer housing  26  provided with an inlet port  28 , a bore  30 , and a tapered section  32 . The piston  20  includes a cylindrical section  34  spaced apart from the inner surface of the bore  30  by a narrow gap, g, such as 50 μm to 250 μm, preferably 100 μm, to form a clearance seal, and an end section  36  having the same shape as the tapered section  32  of the horn  18 . The end section  36  of the piston and the tapered section  32  of the horn define the chamber  12  which receives a desired amount of the drug from the reservoir  14  through the inlet port  28 . A valve  38  is located within the inlet port  28 , or between the port and the reservoir  14 , and is opened and closed under the direction of a controller  39 , such as, for example, a microprocessor, to allow the desired amount of drug into the chamber  12  for each injection. Additionally, there is a ring seal  40  to prevent the drug from escaping from the chamber  12  out between the horn  18  and the piston  20 . 
     The actuator  22  includes one to  10  or more fibers  42  arranged parallel to one another. One end  44  of the fibers  42  is attached to the surface  24  with a clamp  46  and the other end  48  is attached to the piston  20  with another clamp  50  so that the fibers  42  are under tension. Each of the fibers  42  is insulated from the other fibers along its length by an insulating coating. Further, the ends  48  are insulated from each other in the clamp  50 , whereas the ends  44  are in electrical contact with each other through the clamp  46 . When a potential is applied to the ends  44 , the fibers  42  contract to move the piston  20  away from the horn  18 . 
     A class of materials that contract when a potential is applied to them includes piezoelectric crystals and shape memory alloys. While piezoelectric crystals contract about 1%, shape memory alloys are able to contract approximately 5%. The larger contraction of shape memory alloys make them desirable for the illustrated embodiment. Accordingly, the fibers  42  are made of a shape memory alloy such as, for example, Ni—Ti available under the Trade Mark Nitinol. When a potential from a power source  52 , also under the direction of the controller  39 , is applied to the ends  44  of the fibers  42  the fibers heat up. As the fibers heat up, a phase transformation of the fiber material occurs, namely, the fiber changes from martensite to austenite. This phase transformation causes the fibers  42  to contract such that the piston  20  is pulled way from the horn  18 . A more detailed description of shape memory alloys and their use is described in U.S. Pat. No. 5,092,901, the contents of which are incorporated herein in its entirety. 
     In the presently discussed embodiment, the piston  20  and the tapered section  32  of the horn  18  are permanent magnets such that the facing surfaces of the tapered section  32  and the end section  36  are oppositely polarized. Magnetic forces bring the horn and the piston rapidly together when the potential is removed to allow the fibers  42  to relax. Because the magnetic force is inversely related to the square of the distance between the surfaces, the force rapidly increases through the stroke. By using permanent magnets rather than electromagnets, the large mass and power requirements of an electromagnet are avoided, although in some other embodiments, electromagnets are used. Also, in some embodiments, the tapered section  32  is a metal rather than a permanent magnet. 
     The power source  52  includes a super capacitor  53  that is energized by a set of batteries  55 . Accordingly, the potential is applied to the fibers  42  when the super capacitor  53  discharges though a closed switch  56 , and is removed when the super capacitor is being recharged with the batteries  55 . The power source  52  is also provided with an on/off switch  57 . Although any capacitor can be used to apply a potential to the fibers  42  when the capacitor discharges, a super capacitor has the advantageous feature of providing a large energy density in a small physical size. The super capacitor  53  has a volume from 1.5 ml to 30 ml, preferably 3 ml, and an energy output of 10 J to 1 KJ, preferably 100 J. The current applied to the fibers  42  is approximately 100 mAmps to 5 Amps, and the voltage applied to the fibers is between about 1 volt to 10 volts. In one embodiment, the applied current is 1 Amp, and the applied voltage is 5 volts. 
     The fibers  42  have a length, l 1 , of approximately 10 mm to 200 mm, preferably 100 mm that when contracted pulls the piston  20  from the horn  18  by a distance, l 2 , of approximately 0.5 mm to 10 mm, preferably 5 mm. The fibers  42  can have circular cross section, in which case each fiber  42  has a diameter of approximately 0.025 mm to 2 mm. Alternatively, each fiber can have a flat ribbon shape with a thickness approximately in the range 0.025 mm to 0.5 mm and a width of approximately 0.75 mm to 10 mm. Other suitable shape memory alloys include Ag—Cd, Au—Cd, Au—Cu—Zn, Cu—Al, Cu—Al—N, Cu—Zn, Cu—Zn—Al, Cu—Zn—Ga, Cu—Zn—Si, Cu—Zn—Sn, Fe—Pt, Fe—Ni, In—Cd, In—Ti, Ti—Nb, and Ti—Ni. 
     Referring to  FIGS. 2A and 2B , there are shown graphs of the time response of the fibers  42  made from NiTi. Shown in  FIG. 2A  is the response of a fiber subjected to a strain of nearly 5%. As can be seen, the contraction time for this fiber is about 10 ms. By way of contrast,  FIG. 2B  illustrates a fiber subjected to faster pulse than that applied to the fiber of  FIG. 2A . With the faster pulse, the fiber experiences a strain of about 1%, while the contraction time is about 1 ms. 
     In use, the device  10  is typically mounted within applicator that is held by an operator. The applicator is shaped as a pistol, cylinder or any other suitable geometry. Before the operator activates the device  10 , magnetic forces hold the piston  20  and the horn  18  together in a manner such that the end section  36  of the piston  20  is seated and in contact with the tapered section  32  of the horn  18 . 
     The operator positions the applicator such that a surface  60  of the horn  18  is placed against the skin of an animal such as a pig and turns on the device  10  with the switch  57 . The operator then triggers the device  10  such that the controller  38  closes the switch  56  to allow the super capacitor  53  to discharge thereby applying a potential to the fibers  42  which causes them to contract. Hence, as the fibers  42  contract they pull the piston  20  away from the horn  18  to define the chamber  12  between the tapered section  32  of the horn and the end section  36  of the piston. The controller  39  simultaneously instructs the valve  38  to open to allow the drug to flow from the reservoir  14  through the inlet port  28  into the chamber  12 . After a prescribed period of time, the controller  39  directs the valve  38  to close so that a desired amount of the drug is held in the chamber  12  for a single injection. 
     Next, the switch  56  is opened so that the as the batteries  55  recharge the super capacitor  53 , the potential to the fibers  42  is withdrawn, and the fibers  42  relax. As this occurs, because of the magnetic attraction between the horn  18  and the piston  20 , the end section  36  of the piston  20  accelerates towards the tapered section  32 . As the end section  36  and the tapered section  32  come closer together, the volume of the chamber  12  is reduced thereby expelling the drug from the chamber  12  through the orifice  13  into the skin. Note that as the end section  36  and the tapered section  32  come together, the injection pressure applied to the drug through the orifice  13  increases since the speed at which end section  36  moves toward the tapered section  32  increases inversely with the square of the distance between the two. In addition, the particular shape of the tapered section  32  narrows down the acoustic wave to provide higher amplification. The injection pressure is at least 1 MPa and can be as high as 300 MPa. 
     The batteries  55  recharge the super capacitor  53  for the next injection, while the operator removes the applicator from the animal and begins the process with a new animal. In the present application, the reservoir  14  contains enough of the drug for about 100 to 200 injections. When the reservoir  14  is depleted, the operator picks up another applicator to continue with the process. Alternatively, the reservoir  14  can be a removable cartridge that the operator easily exchanges with another cartridge filled with the drug. 
     While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims. For example, in an alternative embodiment, the horn  18  is provided with a pressure or force sensor  100  ( FIG. 1 ) so that the entire injection process described above is automatically triggered. In such an implementation, the operator merely places the surface  60  of the horn  18  against the skin and when the sensor  100  detects that there is an appropriate contact force or pressure between the skin and the surface  60 , the device  10  is triggered to inject the drug into the animal and subsequently re-cocks or re-loads for the next animal. In yet another alternative embodiment, contractile polymers, or any other suitable contracting material, can be used instead of the shape memory alloy.