Abstract
The invention provides methods and apparatus for injecting a medicine, especially a highly viscous medicine. Conventional methods and apparatus for injecting viscous medicines suffers from a variety of problems such as excessive force during the initial needle insertion and initial injection. In an inventive method, during the initial phase of the injection, energy is stored in a torsion spring that is subsequently released during a later stage of the injection. The present invention also provides for an improved autoinjector; especially via the use of a combination compression and torsion spring that powers the injection through controlling force applied to plunger via a screw flange or nut having pins that ride in a prescribed path down the length of the autoinjector.
Claims
1. A method of injecting a medicament from a syringe, comprising: providing a driving force that moves a plunger down a syringe from a distal position toward a proximal position; wherein a torsion spring is attached at a distal end to a first surface and at a proximal end to a second surface; wherein the second surface moves with the plunger; wherein an early stage movement of the plunger toward the proximal position twists the torsion spring to store energy in the spring; and, subsequently, at a later stage, as the driving force continues to move the plunger toward the proximal position, and the second surface moves with the plunger, the torsion spring rotates through a prescribed path to modify the driving force moving the plunger toward the proximal position.
2. The method of claim 1 wherein the torsion spring is a combination torsion and compression spring.
3. The method of claim 2 wherein the combination torsion and compression spring is the only source of providing the driving force.
4. The method of claim 2 wherein, during the later stage, the torsion spring is untwisted to enhance the driving force.
5. The method of claim 2 wherein, once activated, the injection occurs without any power source other than the spring.
6. The method of claim 2 wherein the early stage movement corresponds to an initial period of syringe motion in which the driving force is relatively low in order to insert the needle into the patient's skin this initial period is from activation of the autoinjector to 50 or 100 ms (milliseconds) after activation, or from 0 to 5 mm, or 0 to 10 mm of plunger motion; or wherein during the initial phase the driving force is from 1 to 20 Newtons (N), or from 2 to 10 N, or from 3 to 7 N.
7. The method of claim 2 where potential torsion energy in the spring is increased over the first 50 ms after activation; wherein potential torsion energy in the spring reaches a maximum between about 10 ms and about 1 s after activation, or between about 5 and 50 mm after activation; or between about 5% to about 40% of the full distance traveled during the injection; wherein the potential torsion energy in the spring increases at least 5 N.Math.mm.
8. The method of claim 2 wherein the spring is preloaded with both torsion energy and compression energy.
9. The method of claim 8 wherein the initial potential compression energy is greater than the initial potential torsion energy.
10. The method of claim 2 wherein the potential compression energy in the torsion spring decreases approximately linearly as a function of plunger motion; or wherein, during the second half of the injection (either by time or by plunger motion) the percentage of potential torsion energy in the spring decreases at a rate faster than the percentage of potential linear energy; or wherein, after the initial phase, the driving force increases rapidly, for example, increasing at least 10 N or wherein driving force at least doubles or at least triples, over a distance of 5 mm, or 2 mm, or less, or between 0.1 to 3 mm of plunger motion, or a time of 1 s or less or between 20 ms and 1 s, or between 30 ms and 500 ms; or any combination of these.
11. The method of claim 2 wherein the later stage movement defines an injection phase, and wherein the driving force is reduced by less than 50%, more preferably less than 40%, or less than 20% or between 10 and 40%, or between 5 and 30% during the injection phase; or wherein the driving force is remains between 10 and 200 N, or between 10 and 40 N, or between 20 and 80 N, or between 20 and 40 N during the injection phase.
12. The method of claim 2 wherein, from an activation step through the end of the injection phase, the potential compression energy in the spring is reduced by at least 40%, or at least 50% or from 30% to 90%.
13. The method of claim 3 further comprising a retraction stage, subsequent to the later stage, in which the spring pulls the plunger in the distal direction.
14. The method of claim 13 wherein the second surface is on a nut, wherein the spring is attached to the nut and wherein the prescribed path is controlled by a screw having helical threads; wherein the nut has a pin or pins that ride in the threads of the screw; wherein, during the retraction stage, the pin or pins ride in the threads in a distal direction and wherein the spring provides a torque having a force component in the direction in which the pin or pins ride.
15. The method of claim 1 wherein the spring is attached to a nut and wherein the prescribed path is controlled by a screw having helical threads; wherein the nut has a pin or pins that ride in the threads of the screw; wherein the helical threads have a thread angle α that varies along the length of the screw.
16-32. (canceled)
33. A method of injecting a medicament from a syringe, comprising: providing a driving force that inserts a needle at the proximal end of the device, then subsequently moves a plunger down a syringe from a distal position toward a proximal position; wherein a spring having both a torsion mode and a compression mode is attached at one end to a first surface and at one end to a second surface; wherein the second surface moves with the plunger and an early stage movement of the plunger toward the proximal position twists the torsion spring to store energy in the spring; and subsequently as the driving force due to the compression mode continues to move the plunger toward the proximal position, and the second surface moves with the plunger, the torsion mode of the spring rotates thru a prescribed path to modify the driving force moving the plunger toward the proximal position.
34. The method of claim 33 wherein the insertion of the needle is accomplished by transferring energy from the compression mode of the spring to the torsion mode spring in order to optimize force needed for needle insertion.
35-36. (canceled)
37. The method of claim 33 where the coil spring wire has a square cross section.
38. The method of claim 33 wherein the step in which the torsion mode of the spring rotates through a prescribed path to modify the driving force comprises untwisting the spring to release energy from the spring to enhance the driving force moving the plunger toward the proximal position.
39-40. (canceled)
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0038] FIG. 1 illustrates an exploded side view of an autoinjector.
[0039] FIG. 2A illustrates device activation. FIG. 2B illustrates a non-exploded side view of the autoinjector of FIG. 1.
[0040] FIG. 3 is a schematic cross-sectional view of an autoinjector having a central, fixed screw.
[0041] FIG. 4A illustrates a cross sectional view of an autoinjector. FIG. 4B illustrates an external view of an autoinjector.
[0042] FIG. 5 is a schematic cross-sectional view of a jewel bearing that provides for low friction rotation of a plunger within a syringe.
[0043] FIG. 6 illustrates a nut that rides down a fixed screw.
[0044] FIG. 7 illustrates a fixed screw having grooves in which pins on a nut ride down the screw.
[0045] FIG. 8 illustrates a plunger.
[0046] FIG. 9 illustrates motion of a nut riding down a screw.
[0047] FIG. 10 is a schematic cross-sectional view of an autoinjector prior to activation.
[0048] FIG. 11 is a schematic cross-sectional view of an autoinjector prior after activation.
[0049] FIG. 12 illustrates an exploded view of a release button.
[0050] FIG. 13 is an exemplary plot of force versus plunger motion.
[0051] FIG. 14 is an exemplary plot of work out, potential energy of the spring (compression and torsion components) and friction loss.
[0052] FIG. 15 is an exemplary plot of screw angle (also known as thread angle) versus plunger motion.
[0053] FIG. 16 is an exemplary plot of screw lead (axial travel for a single revolution) versus plunger motion.
[0054] FIG. 17A shows a view of the screw with regions for needle insertion, fluid delivery, and needle retraction. FIG. 17B is a view showing thread grooves around the central axis.
[0055] FIG. 18 shows force and energy as a function of plunger motion during insertion, delivery and retraction.
[0056] FIG. 19 shows the relationship between thread (screw) angle and plunger motion.
[0057] FIG. 20 shows the end of a plunger with a plunger cap.
[0058] FIGS. 21-22 compare the measured force output (in N) versus distance of plunger rod travel for 25N and 50N combination compression/torsion springs used in the present invention and the same force springs used only in compression.
[0059] FIGS. 23-25 show geometry and forces of a free body analysis of a preferred embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0060] FIGS. 1, 2, 4, 5, and 12 illustrate one embodiment of the invention. To operate the device, the user will typically remove it from packaging and allow it to equilibrate to room temperature if stored refrigerated. A sterile needle shield cover would be removed (not shown) to expose the needle. To use the device the user would first prepare the injection site (e.g., abdomen, thigh, arm) and locate the proximal end of the device against the injection site. To operate the device, the user turns the unlock collar. Turning (step 1 in FIG. 2A) the unlock collar 10 lifts the lock plate 12 using ramps 10a so the keyway 12a on the lock plate exits the key on the plunger screw 14a that includes screw flange 15. Turning the unlock collar also rotates the button 16 which moves the bottom of the button 16b away from the support ledge 20a and allows it to move freely in the axial direction. In this state, the device is unlocked, but will not actuate. To actuate the device, the user depresses the button 16 (step 2 in FIG. 2A). The ramps 16a on the button cause the plunger screw to rotate. The plunger screw 14 then travels both axially and rotationally down the nut due to both the force and torque applied by the drive spring 22. The initial portion of the movement inserts the needle into the patient's skin to the proper depth. After this depth is achieved, the remainder of the movement expels drug into the patient. Optionally, a needle retraction feature (discussed below) and safety lockout mechanism (not shown) could be added so that the device could be safely disposed of after use.
[0061] The device additionally comprises casing 18, which, in the illustrated embodiment, includes sleeve 20 and button 16 and lock plate 12. The invention is sometimes described as having a spring 22 connected to the sleeve 20; this means that the spring is either directly attached to the sleeve or attached to a stationary structure (such as an internal flange) that is, in turn, connected to the sleeve. The casing surrounds the sleeve which can be split into multiple pieces for improved manufacturability. Tabs 25 on the spring can be passed through holes in a suitable structure such as flange 27 and movable nut 29.
[0062] FIG. 4 shows an outer view (right side) and cross-sectional view (left side) of a portion of an injector including a nut 42 having grooves 44 that include an upper (first) portion having a relatively steep groove 46 in a direction that cooperates with screw flange 15 to slow the plunger 48 and store energy in torsion spring 50. At location 52, a knee in the groove reverses the twist direction of the torsion spring. In the lower (second) portion 54, the torsion spring untwists and releases energy into the spring to maintain a constant or nearly constant force that pushes the plunger into the syringe and thus maintains a constant flow of medicine out of the syringe throughout the injection. The release of energy is further aided by controlling the angles of the thread in the lower portion. The screw flange 15, plunger rod 48, torsion (or typically combination torsion and compression) spring 50, and nut 42 form a plunger movement assembly 62. Because the plunger screw 14 is rotated, it is desirable to have a bearing 64 to facilitate rotation of the plunger rod within the syringe 58. Another possibility is to place a bearing between the plunger rod and the screw flange.
[0063] A schematic illustration of a bearing assembly 66 is shown in FIG. 5. The plunger rod 48 terminates at the proximal end in a knob 68. A jewel bearing 71 is formed by the knob disposed in cage 72 having a sufficiently large inner diameter to allow the presence of a small space 74 between the knob and the cage allowing the plunger rod to rotate freely while also translating down the axis of the syringe 76, and the lower surface 78 of the cage effectively forms the bottom surface of the plunger at the point in which plunger and medicament 80 in the syringe contact each other. An upper flange 82 on the syringe within clamp 84 forms a seal and maintains the connection between the syringe and the plunger rod 48 and also plunger movement assembly 62.
[0064] A drawing of a preferred embodiment of the inventive injector apparatus is illustrated in FIGS. 3 and 6-11. An elongated housing 102 contains a combination torsion and compression spring 22, a threaded screw 104, a syringe carrier 111, a nut 106 disposed around the screw, a plunger rod 108, and a syringe 110. In operation, the syringe includes a hollow needle (not shown) affixed to the proximal end of the syringe. The housing should be rigid enough to withstand a person gripping the housing without substantial deformation that would inhibit spring action. The illustrated housing only partly encloses the syringe; however, the housing could alternatively be extended to enclose the syringe and, optionally, the needle. In another alternative, the entire device could be disposed within a larger housing unit (not shown). The combination torsion and compression spring is disposed about the screw and is affixed at the distal end to the housing and at the proximal end to the nut. Prior to injection, the spring is held in place by a spring stop. For operation, the user will press a button or activate a lever, etc. (not shown) to move the spring stop and release the spring. The key 112 on the plunger rod allows the syringe to be supported prior to activation so that the needle does not protrude from the device before the user begins an injection. During storage, the key keeps it rotationally aligned with the body of the device. The nut has a generally cylindrical shape and a pair of projections 114 that ride in the threads of the screw. The spring propels the nut down the shaft of the screw. The screw is fixed within the housing, typically by a flange 116 that is affixed to the distal end of the housing. The screw has a knee 118 at that reverses the direction of the nut as it rides down the screw. In preferred embodiments, as the nut initially rides down the screw, the threads 120 are very steep so that the needle advances in a controlled manner with a relatively small force. The threads cause the nut to rotate in a direction to twist and thus store additional torsional energy in the spring. Once the needle is fully advanced, the driving force increases rapidly. In the initial phase the compression force from the spring is at its highest, then as the plunger continues to advance in the proximal direction, the compression force available from the spring drops and, after the nut passes the knee in the screw, the spring untwists and torsion energy is released causing an increase in the driving force pushing the plunger in the proximal direction.
[0065] The nut can be physically attached to the plunger rod or could press against the plunger rod (either directly or through an intervening component). In the illustrated embodiment, clip 124 secures flange 126 on the plunger 108. The motion of the nut pushes the plunger rod, which, in an initial stage pushes the syringe forward in the housing to advance the needle into the patient. The syringe could be held by a slidable disk that slides within the housing it is reaches a stop. Once the syringe is stopped, the plunger pushes medicine out of the syringe through the needle. The plunger rod is rigid, cylindrical and disposed about the screw.
[0066] In another alternative embodiment, the user can twist the spring and thus control the initial extent of torsional energy stored in the spring at the start of injection.
[0067] The selection of materials for the injector device can be selected by the skilled engineer. In some embodiments, a lubricant (such as silicone oil) is disposed between surfaces that slide over each other during operation.
[0068] The medicine within the syringe could be any solution or suspension; but the invention is especially advantageous for the delivery of a liquid having an absolute viscosity greater than 20 cP. Absolute viscosity can be measured by capillary rheometer, cone and plate rheometer, or any other known method. Preferably, the viscous solution comprises a protein suspension. Exemplary plots of force versus plunger motion that are within the scope of the present invention are shown in FIG. 13. The invention includes force and/or work versus motion profiles that correlate with any of the plots described herein, either qualitatively or within 20% (or within 10%) of the values shown here. For example, the invention includes methods of injecting a medicament from a syringe possessing one or any combination of the following characteristics: an initial period of syringe motion in which the driving force is relatively low in order to insert the needle into the patient's skin (for example between about 5% to 50% of the maximum driving force and/or the average force (averaged either over the time of injection or the distance of injection) or between about 10% and about 40%, or between about 10% and 30%, or between about 15% and 30%) and in preferred embodiments this initial period is from activation of the autoinjector to 50 or 100 ms (milliseconds) after activation (or within the range of 5 ms to 50 ms), or from 0 to 5 mm, or 0 to 10 mm of plunger motion; or a speed of 200 mm/s to 4000 mm/s during the insertion; wherein during the initial phase the driving force is from 1 to 20 Newtons (N), or from 2 to 10 N, or from 3 to 7 N; where potential torsion energy in the spring is increased over the first 50 or 100 ms after activation, or from 0 to 5 mm, or 0 to 10 mm, or from 0 to about 15 mm, or from about 0 to 25 mm; wherein potential torsion energy in the spring reaches a maximum of about 10 mm and about 7 ms (or between 5 ms and 50 ms) after activation, or between about 5 and 50 mm, or between about 5 mm and 30 mm, or between about 5 mm to 20 mm after activation; or between about 5% to about 40% of the full distance traveled during the injection; wherein the potential torsion energy in the spring increases at least 5 N.Math.mm or at least 10 N.Math.mm, or between 10 and 500 N.Math.mm, or between 15 and 300 N.Math.mm, or between 20 and 200 N.Math.mm; wherein the spring is preloaded with both torsion energy and compression energy; wherein the initial potential compression energy is greater than the initial potential torsion energy; wherein the potential compression energy decreases approximately linearly as a function of plunger motion; wherein, during the second half of the injection (either by time or by plunger motion) the percentage of potential torsion energy in the spring decreases at a rate faster than the percentage of potential linear energy; wherein, after the initial phase, the driving force increases rapidly, for example, increasing at least 10 N or wherein driving force at least doubles or at least triples, over a distance of 5 mm, or 2 mm, or less, or between 0.1 to 3 mm of plunger motion, or a time of 1 s or less or between 20 ms and 1 s, or between 30 ms and 500 ms; wherein the driving force is reduced by less than 50%, more preferably less than 40%, in some embodiments less than 20% and in some embodiments between 10 and 40%, or 5 and 30% during the injection phase; wherein the driving force is remains between 10 and 200 N, or between 10 and 40 N, or between 20 and 80 N, or between 20 and 40 N during the injection phase; and wherein, from the activation step through the end of the injection phase, the potential compression energy in the spring is reduced by at least 40%, or at least 50% or from 30% to 90%.
[0069] An exemplary plot of work out in a preferred embodiment is shown in FIG. 14. As can be seen, after an initial stage, work out as a function of length is linear (derivation of slope is zero). Potential energy of the spring (compression and torsion components) and friction loss.
[0070] An exemplary plot of screw angle (also known as thread angle) versus plunger motion, that is within the scope of the present invention, is shown in FIG. 15. An exemplary plot of screw lead (axial travel for a single revolution) versus plunger motion, that is within the scope of the present invention, is shown in FIG. 16. These plots are not limiting but show examples of the characteristics of some preferred embodiments of the invention. In some preferred embodiments of the invention, in the initial phase, the screw angle is in the range of −70 to −20 degrees, in some embodiments from −60 to −30 degrees; then for the second (injection) phase, the screw angle is positive, in some embodiments 10 degrees or more, in some embodiments in the range between 10 and 80 degrees. In some preferred embodiments of the invention, in the initial phase, the screw's lead is negative and in some embodiments is between 10 and 120 mm, in some embodiments between 20 and 80 mm, or between 30 and 70 mm; in some embodiments, the lead decreases during the initial phase, in some preferred embodiments, this decrease is approximately monotonic, preferably with a decrease of about 5 mm to about 40 mm; then for the second (injection) phase, the screw lead is positive for at least a portion of the injection, preferably for the entire injection, and is preferably between 2 and 500 mm, in some embodiments between 10 and 300 mm, or between 15 and 200 mm; in some embodiments, the lead decreases during the second phase, in some preferred embodiments, this decrease is approximately monotonic, preferably with an decrease of at least about 20 mm or at least about 50 mm, or in the range of about 20 mm to about 300 mm, or 10 mm to 150 mm over the length of the second phase. In some embodiments, the lead decreases during the second phase from about 170±40 mm to about 20±40 mm over the length of the second phase. The second phase refers to the injection phase.
Retraction Load Path
[0071] An example of a reversing thread path and corresponding plots of force versus plunger motion, and screw angle versus plunger motion are shown in FIGS. 17-20. As described above, there is an initial portion for needle insertion 171, and a fluid delivery portion 173 where the thread path provides for relatively constant force during the course of the injection. In the illustrated embodiment, a reversing thread path 175 (needle retract) is added to provide for needle retraction at the end of the injection. During the retraction, the screw angle and force become negative; the nut reverses course and moves toward the distal end of the injector. Since there is no hydraulic load in the reverse direction, the plunger screw quickly retracts. The nut, foot, and syringe carrier all move in the distal direction on retraction. As shown in FIG. 20, the proximal end of the plunger has a foot 201, thread 203 and piston cap 205 that fits tightly within the syringe barrel 207. The friction between the plunger and the syringe barrel is typically much greater than the friction to withdraw the needle from the skin which causes the syringe to move in the reverse direction with the piston. As the syringe is withdrawn, the pressure within the syringe is quickly relieved from the syringe contents which stops delivery of fluid. At the end of the retraction, the torsion spring could lock the mechanism into a rotational detent position, thus locking the syringe in the retracted state.
Test Data
[0072] The combination compression/torsion spring was tested in conjunction with a plunger screw, nut and roller bearings. FIGS. 21-22 compare the measured force output (in N) versus distance of plunger rod travel for the combination compression/torsion springs used in the present invention and the same springs used only in compression. As can be seen, for both 25 N and 50 N springs, the combination compression/torsion springs used in the present invention provide greater and more constant force over the length of the simulated injection. The inventive configuration provided a near plateau, with less than a 20% decrease in force over the length of a simulated injection while the straight compression spring shows about a 50% decrease in force over the length of the simulated injection. As a result, the inventive configuration will provide a faster, smoother, and/or more complete injection as compared with a device powered by a conventional compression spring.
[0073] A free body diagram analysis is useful for determining forces, torques and friction loads on the autoinjector mechanism based on the characteristics of the geometry (i.e. radius, thread pitch, etc.) By taking each component and examining the applied forces and torques at each physical interface, a mathematical relationship can be developed. From these equations, the characteristics can be explored and the design can be adjusted to achieve the desired results. The free body analysis presented below was used to develop the theoretical performance curves presented in FIGS. 13 thru 16 based on a preferred embodiment. FIGS. 23 thru 25 show the preferred ranges of forces, torques, energy and screw geometry.
[0074] In some instances, preferred embodiments of the invention can be characterized by the following geometry including a threaded screw and the corresponding equations:
[0075] The following list of terms relates to the embodiment having the type of geometry illustrated in FIG. A-C.
[0076] F.sub.s=force applied by spring
[0077] T.sub.s=torque applied by spring
[0078] F.sub.T=force on thread
[0079] R.sub.T=radius of thread
[0080] μ.sub.T=friction coefficient of thread
[0081] α=angle of thread
[0082] F.sub.B=force on bearing
[0083] R.sub.B=radius of bearing
[0084] μ.sub.B=friction coefficient of bearing
[0085] F.sub.K=force on key
[0086] R.sub.K=radius of key
[0087] μ.sub.k=friction coefficient of key
[0088] F.sub.out=force output
The various forces and torques in the autoinjector can be understood using free body diagrams as follows:
Free body diagram of the Nut:
Sum of forces in the Y direction must equal zero:
(μ.sub.TF.sub.T)cos α−F.sub.T sin α+F.sub.B—F.sub.s=0
F.sub.T=(F.sub.s−F.sub.B)/((μ.sub.T)cos α−sin α)
Sum of torques must equal zero:
T.sub.s−(μ.sub.TF.sub.TR.sub.T)sin α−(F.sub.TR.sub.T)cos α−μ.sub.BF.sub.BR.sub.B=0
T.sub.s=F.sub.TR.sub.T((μ.sub.T)sin α+cos α)+μ.sub.BF.sub.BR.sub.B
Combining forces and torques:
T.sub.s=R.sub.T(F.sub.s−F.sub.B)/(((μ.sub.T)sin α+cos α)/((μ.sub.T)cos α−sin α))+μ.sub.BF.sub.BR.sub.B
β=((μ.sub.T)sin α+cos α)/((μ.sub.T)cos α−sin α)=((μ.sub.T)Tan α+1)/(μ.sub.T−Tan α)
F.sub.B=(T.sub.s−R.sub.TF.sub.sβ)/(μ.sub.BR.sub.B−R.sub.Tβ)
Free Body Diagram of the plunger rod:
Sum of torques must equal zero:
μ.sub.BF.sub.BR.sub.B=F.sub.KR.sub.K
F.sub.K=μ.sub.BF.sub.BR.sub.B/R.sub.K
Sum of forces must equal zero:
F.sub.out=F.sub.B−μ.sub.KF.sub.K
Combining forces and torques:
F.sub.out=F.sub.B(1−μ.sub.Kμ.sub.BR.sub.B/R.sub.K)
In some embodiments, the inventive methods and apparatus may be characterized by full or partial conformance with the features described in the forgoing free body analysis.
