WO2007059005A2

WO2007059005A2 - Lateral side ported needle

Info

Publication number: WO2007059005A2
Application number: PCT/US2006/043926
Authority: WO
Inventors: C. Robin Hwang; Michael Akers; Ajit Pandey
Original assignee: Amgen Inc.
Priority date: 2005-11-15
Filing date: 2006-11-13
Publication date: 2007-05-24
Also published as: WO2007059005A3

Abstract

A needle (10) for delivering a fluid to a body includes a shaft (14) having a proximal end (16) , a distal end (12) , and a hollow bore (18) that extends from the proximal end (16) to the distal end (12) . The proximal end (16) is configured to place a fluid reservoir in fluid communication with the hollow bore, and the distal end is configured to penetrate the body. The needle (10) may include at least two groups of side apertures (22) in the shaft, each group of side apertures including at least two laterally aligned side apertures to provide fluid communication between the hollow bore and an exterior of the shaft. Alternatively, the needle may include at least one group of laterally aligned side apertures, the laterally aligned side apertures being positioned at least about 4.5 mm from the proximal end of the needle to permit sub-dermal delivery of fluid.

Description

Lateral Side Ported Needle

This application claims priority to U.S. Provisional Patent Application No. 60/736,305, filed on November 15, 2005.

Description

Field of the Invention

[01] The present invention relates to a needle for delivery of a fluid to the body, and more particularly, to a needle having reduced injection pressure from automated injection systems.

Background of the Invention

[02] Needles have traditionally been designed to deliver aqueous fluids to the body. Typically the needle includes a sharpened distal end and a proximal end fluidly connected to a fluid reservoir. In operation, the sharpened distal end of the needle is able to pierce the body. The fluid contained within the reservoir may then be delivered to the body through an aperture in the distal end of the needle.

[03] The development of drugs, formulations, and therapeutics for chronic conditions has spurred demand for improved medication delivery systems. To facilitate timely drug delivery and reduce patient reliance on health care professionals, it may be desirable to allow patients to self-inject medication. To improve patient compliance, simple, easy-to-use and low-cost automated injection systems have been developed for drug delivery. Automated injection systems include auto-injectors, injector "pens," and other patient-operated drug delivery devices. However, a significant limitation to the widespread adoption of auto-injectors has been pain associated with needle piercing and medication delivery to the body.

[04] In order to reduce the pain associated with drug delivery, smaller needles are used. There has been a general trend toward smaller diameter (i.e., higher gauge) needles to minimize pain associated with fluid injection. For example, U.S. Patent 6,146,361 describes a 31 gauge needle used in combination with drug delivery pen designed to reduce pain. [05] Pain reduction also has also been achieved through the use of side ported needles. Needles with side ports, or side apertures, designed to reduce pain associated with fluid delivery have been described. For example, a needle designed to reduce trauma associated with anesthesia injection included a tip designed to allow the needle to pass between nerve fascicles. Subsequent anesthesia injection occurs through one or more of the side ports, reducing the pressure imparted on the nerve fascicles by the injected anesthesia."

[06] Needles with side ports have also been used for fluid delivery to specific locations within the skin. For example, a needle with one or more side ports for subcutaneous fluid delivery has been described in the prior art. The needle was designed for use with a drug infusion system, where injection times can be minutes or hours. Other side ported needles were designed for epidermal fluid delivery, where the penetration length of the needle is less than approximately 4.5 mm.

[07] Other needles with side apertures include hypodermic needles having a main bore containing a tapered section where the outside needle diameter decreases toward the distal tip of the needle. The tapering is designed to reduce pain or trauma associated with skin penetration.

[08] The majority of needles listed above describe needles designed to, inject aqueous solutions or formulations with a viscosity close to that of water. Injection of more viscous fluids generally requires a relatively high injection force if larger needles and/or long injection times are to be avoided. However, high injection forces can require larger springs or other means to generate the injection forces and more robust auto-injectors. In addition, the high injection forces may crack or shatter the reservoirs containing the fluid to be injected.

[09] Auto-injectors generally require high injection forces to deliver high viscosity fluids. If the auto-injector utilizes springs to provide injection force, springs with high spring constants are generally needed. In order to accommodate high injection forces, auto-injectors often require significant design modifications. For example, auto-injectors containing springs with high spring constants may require increased size and weight to accommodate additional forces acting on the auto-injector. Further, high injection forces may crack or shatter fluid reservoirs. For these and other reasons it is desirable to lower injection forces and pressures. [10] Current needle designs suitable for use with auto-injectors suffer a number of deficiencies. Current needle designs require high injection force to expel fluids in the appropriate amount of time. Injection forces may be lowered by moving to lower gauge needles; however, these larger needles can cause increased pain. Longer injection times can reduce injection force, but long injection times are not well tolerated by patients. There exists the need to lower the injection force capable of injecting viscous fluids using auto- injectors.

Summary of the Invention

[11] One aspect of the present disclosure is directed toward a needle for delivering a fluid to a body. The needle includes a shaft having a proximal end, a distal end, and a hollow bore that extends from the proximal end to the distal end. The proximal end is configured to place a fluid reservoir in fluid communication with the hollow bore, and the distal end is configured to penetrate the body. The needle also includes at least two groups of side apertures in the shaft. Each group of side apertures has at least two laterally aligned side apertures configured to permit fluid communication between the hollow bore and an exterior of the shaft.

[12] Another aspect of the present disclosure is directed toward an injection needle for sub-dermal delivery of a fluid to a body. The needle includes a shaft having a proximal end, a distal end, and a hollow bore extending from the proximal end to the distal end. The proximal end is configured to place a fluid reservoir in fluid communication with the hollow bore, and the distal end is configured to penetrate the body. The needle also includes at least one group of side apertures in the shaft. The at least one group of side apertures is positioned at least approximately 4.5 mm from the proximal end of the shaft to permit sub-dermal delivery of fluid to the body, and includes at least two laterally aligned side apertures configured to place the hollow bore in fluid communication with an exterior of the shaft.

[13] Another aspect of the present disclosure is directed toward a method for determining a parameter of a fluid delivery device. The method includes creating a computational representation of the needle to be tested. A computational mesh is applied to the computational representation of the needle to be tested. The method also includes modeling fluid flow using one or more fluid parameters, and determining at least one of an injection parameter or a needle parameter of the fluid delivery device.

[14] Additional objects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims.

[15] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.

Brief Description of the Drawings

[16] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate various embodiments of the invention and together with the description, serve to explain the principles of the invention, hi the drawings, [17] Fig. 1 is a view of a needle according to an illustrative embodiment of the invention; [18] Fig. 2 is a top and side view of the needle of Fig. 1, according to an illustrative embodiment of the invention; [19] Fig. 3 A is a cross-section of a shaft of a needle according to the present invention, taken along line 3 A-3 A in Fig. 2; [20] Fig. 3B is a cross-section of an alternative embodiment of the shaft of the needle depicted in Fig. 2; [21] Fig. 3 C is a cross-section of yet another alternative embodiment of the shaft of the needle depicted in Fig. 2; [22] Fig. 4 is a graph of a flow rate distribution for a 27 gauge needle according to an illustrative embodiment of the invention; [23] Fig. 5 is a graph showing flow rate distributions for 23 and 27 gauge needles according to illustrative embodiments of the invention; and [24] Fig. 6 is a graph showing flow rate distributions for 23 and 27 gauge needles according to illustrative embodiments of the invention. Description of the Embodiments

[25] Reference will now be made in detail to the various embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.

[26] The present invention is directed towards a needle for delivery fluid to the body. The needle includes a plurality of apertures in its body that are positioned so as to permit sub-dermal delivery of a viscous fluid by an injection system used with the needle. The alignment and distribution of the apertures can be such that the injection forces needed to deliver the fluid through the needle, even allowing for the delivery of viscous fluid, are less than the injection forces associated with the operation of conventional needles. The position and alignment of the apertures may be determined by use of computer simulation of the injection process.

[27] Side ports, or side apertures along the body of the needles, may reduce injection forces by increasing the area through which the injected fluid exits the needle. In addition, side ports allow fluid delivery to a larger area of surrounding tissue than non-side ported needles. Fluid delivery to a larger area may reduce injection force and pressure. Specifically, the fluid may disperse along the path of least resistance, which may lie along the lamellar orientation of tissue. Side apertures may also reduce injection forces by reducing the possibility of port occlusion, which raises injection pressure. There is a greater likelihood that a needle's single distal opening would be occluded when compared to a needle having a plurality of openings. Thus, side ports might allow fluid delivery through apertures unaffected by occlusion.

[28] With reference to the drawings, Figs. 1 and 2 show a needle 10, in accordance with an exemplary embodiment of the present invention. Needle 10 includes a distal end 12, a shaft 14, and a proximal end 16. Needle 10 also includes a hollow bore 18 that opens at a proximal aperture 21 in proximal end 16 and passes through shaft 14 to distal end 12 and ends in a distal aperture 20. At least two groups of side apertures 22 maybe provided along the length of shaft 14. It is also contemplated that needle 10 may include ,a single group of side apertures 22. Alternatively, more than two groups of apertures 22 may be provided. [29] As embodied herein and shown in Figs. 1 and 2, shaft 14 may include two groups of side apertures 22, a group of distal side apertures 24 and a group of proximal side apertures 26. The group of distal side apertures 24 may include two distal apertures 24a, 24b and the group of proximal side apertures 26 may include two proximal side apertures 26a, 26b. Either group may be provided with one or more than two apertures. Bore 18 is in fluid communication with distal aperture 20, the groups of side apertures 22 and proximal aperture 21.

[30] Distal end 12 of needle 10 is configured to aid insertion of needle 10 into the body. Specifically, distal end 12 may be shaped to reduce the pain and trauma associated with needle insertion. For example, distal end 12 may include a beveled tip or other appropriate tip design to reduce pain and/or aid fluid injection. Distal end 12 may or may not include distal aperture 20. It is also contemplated that distal end 12 may be tapered.

[31] Proximal end 16 may include a structure to fluidly connect proximal aperture

21 with a fluid reservoir (not shown). Proximal end 16 may include a permanent connection with a fluid reservoir, such as, for example, a canister containing a drug formulation. It is contemplated that proximal end 16 may include a Luer lock, or any other suitable means to connect needle 10 to a fluid reservoir. Needle 10 may be fluidly connected to a syringe (not shown), wherein the syringe can be at least partially formed from any material known in the art, such as, glass or plastic (e.g. cyclic olefin copolymer or cyclic olefin polymer). It is also contemplated that proximal end 16 may connect to an auto-injector, infusion device, or similar device designed to receive replaceable fluid reservoirs. For example, needle 10 may be attached to an auto-injector using the SureClick™ system available from Amgen (Thousand Oaks, CA) or the Penfine® universal click™ system available from Ypsomed (Bergdorf, Switzerland).

[32] Shaft 14 may be any appropriate length and diameter as can be determined by specific application. For example, a sub-dermal needle will typically require injection depth of greater than approximately 4.5 mm. For sub-dermal fluid delivery, the length between the proximal end of proximal side apertures 26a, 26b and the proximal end 16 could be greater than approximately 4.5 mm. It is also contemplated that needle 10 may be used for intradermal and other types of fluid delivery to a body and the length, size, location and configuration of side apertures may be designed accordingly. [33] The diameter of shaft 14 may also be modified as can be determined by application. For example, a patient population may require a needle of specific length to deliver a formulation to a desired depth beneath the skin. Structural considerations resulting from the needle length may restrict the needle to a minimum diameter. However, generally smaller shaft diameters reduce the pain associated with fluid injection. By contrast, larger needle diameters may reduce injection times and/or the forces involved with fluid delivery. These and other factors may affect the diameter of shaft 14. Current auto-injectors generally utilize needles of gauge 18 - 33 (i.e., about 0.838 - about 0.089 mm nominal outer diameter). It is contemplated that the diameter of needle 10 may be between gauges 18 - 33, and in other embodiments the diameter of needle 10 may be between gauges 23 -. 27 (i.e., about 0.318 - about 0.191 mm nominal outer diameter). The diameter of needle 10 may be non-uniform, such as, for example, tapered. The shape of needle 10 may be bent, such as, for example, a Tuohy needle.

[34] Extending through shaft 14 is hollow bore 18. Bore 18 fluidly connects distal aperture 20, groups of side apertures 22 and proximal aperture 21. Bore 18 may be any appropriate diameter as necessitated by the type of fluid to be injected, the outside diameter of shaft 14, and/or the forces to be applied to needle 10. Larger bore diameters create less resistance to fluid flow, reducing injection times and/or injection force. Bore diameters may be constrained by the injection forces and fluid pressures exerted on the walls of bore 18 during fluid injection. Bore diameter may also be constrained by the type of injection device and needle insertion method. For example, an auto-injector that injects needle 10 at high velocity may require the walls of bore 18 (which form shaft 14) to be sufficiently thick to withstand the forces applied. The thickness of the walls of shaft 14 may also be affected by the dimensions, location and number of side apertures. One or more of these factors may influence the diameter of bore 18.

[35] Needle 10 may include at least two groups of side apertures 22. As shown in

Figs. 1 and 2, groups of side apertures 22 may include a pair of distal side apertures 24a, 24b and a pair of proximal side apertures 26a, 26b. Each aperture is in fluid communication with bore 18. In one embodiment, the distal side apertures 24a, 24b may be laterally aligned with one another. Additionally, the proximal side apertures may be laterally aligned with one another. Use of the term "laterally aligned" herein refers to the positioning of two or more side apertures such that they may be intersected by the same imaginary lateral plane perpendicular to the longitudinal axis of shaft 14. Thus, "aligned" does not always require that centers of these side apertures are coaxial. Rather, "aligned" means that a portion of one side aperture occupies the same lateral position of the needle along the length of the shaft 14 as another side aperture. These apertures may be considered to be laterally aligned and to occupy the same lateral region of the needle. The lateral region can be defined by the longitudinal boundaries of a particular aperture. For example, as shown in Fig. 2, distal apertures 24a and 24b are laterally aligned apertures as both apertures are located within the same lateral region bounded by the distal and proximal longitudinal ends of distal apertures 24a and 24b. Distal side aperture 24a and proximal side aperture 26a are not laterally aligned apertures as the apertures are not positioned such that they both intersect the same imaginary lateral plane perpendicular to the longitudinal axis of shaft 14. That is, there is no overlap in the lateral direction between distal aperture 24a and proximal aperture 26a. Specifically, the location of the proximal end of distal side aperture 24a does not extend beyond the location of the distal end of proximal side aperture 26a in the longitudinal direction. It is contemplated that laterally aligned apertures may be positioned at locations along the length of needle 10 that partially overlap. In particular, the distal longitudinal ends or the proximal longitudinal ends of laterally aligned apertures may not lie in the same lateral planes. The overlapping laterally aligned side apertures may be positioned along shaft 14 so that the proximal longitudinal end of a first aperture is positioned between the proximal and distal longitudinal end of a second aperture.

[36] As embodied herein and shown in Figs. 1 and 2, groups of side apertures 22 may each include two laterally aligned apertures. It is also contemplated that needle 10 may include a single group of laterally aligned side apertures 22. As shown in Fig. 2, distal side apertures 24a, 24b are laterally aligned with one another, and proximal side apertures 26a, 26b are laterally aligned with one another. Although not shown, it is also possible that one or more of the distal side apertures 24a, 24b are laterally aligned with the proximal side apertures 26a, 26b. Apertures 24a, 24b, 26a, and 26b are each in fluid communication with bore 18 and fluidly connect bore 18 with regions external to shaft 14. Each set of laterally aligned side apertures 24a, 24b and 26a, 26b may include apertures of equal or different length in the x-direction or longitudinal direction, and equal or different width in the y- direction or lateral direction, spaced around shaft 14 and fluidly connected to bore 18. For example, Figs. 1, 2 and 3 A show groups of side apertures 22 including two pairs of laterally aligned apertures of the same size and shape. Alternatively, each side aperture of a pair of laterally aligned side apertures may be of a different size and/or shape than the other aperture of the pair.

[37] With reference to the drawings, Figs. 3A, 3B and 3C show alternative cross sectional views of needle 10, in accordance with three embodiments of the present invention. Figs. 3B and 3C show the cross-section of shaft 14 having three and four laterally aligned apertures, respectively. For example, as shown in Fig. 3B, three laterally aligned apertures 27a, 27b, and 27c may be provided. Alternatively, as shown in Fig. 3C, the shaft 14 may include four laterally aligned side apertures 28a, 28b, 28c, and 28d. It is contemplated that more than four apertures may be provided. Further, the laterally aligned side apertures may be spaced in regular or irregular intervals around shaft 14. It is also contemplated that side apertures may be located at an angle to the longitudinal axis of shaft 14.

[38] Laterally aligned apertures of groups of side apertures 22 may have any cross-sectional profile. The cross-sectional profile includes the cross section of laterally aligned apertures in the x and y direction. For example, laterally aligned apertures may be beveled, tapered, rounded, etc. Groups of side apertures 22 may also be designed for manufacturability. Specifically, side apertures may be elliptical, rectangular, or any shape capable of routine manufacture.

[39] Side apertures may be any shape and size. For example, side apertures may be elongated openings in shaft 14 extending along the longitudinal axis (or x axis) of needle 10. The dimensions of the side apertures of groups of side apertures 22 may be longer in the x direction than the y direction. For example, the ratio of lateral dimension to longitudinal dimension may be between approximately 1 :2 and approximately 1 :200. Laterally aligned side apertures may be irregularly shaped. Specifically, side apertures may be tapered at the distal and/or proximal ends.

[40] The number, location, configuration, shape and/or size of side apertures may be designed to significantly reduce the injection forces generated by movement of fluid through needle 10. It is contemplated that the cross-sectional areas of side apertures may significantly increase the area available for fluid flow from needle 10. For example, the ratio of combined groups of side apertures 22 area to the area of distal aperture 20 maybe about 5:1 or greater. The increased fluid flow area may reduce the forces resisting fluid flow, reducing the injection pressure. The reduced injection forces may allow shorter injection times, smaller needles, reduced spring constants, and/or smaller auto-injectors.

[41] Needle 10 may be manufactured from any suitable material, such as, for example, a metal, alloy, polymer, ceramic, etc. It is also contemplated that needle 10 may be manufactured from composite material and/or contain different regions of different materials. For example, the distal region may be ceramic to reduce tip wear while the proximal region may be a metal alloy for structural requirements. Needle 10 may also be coated with a suitable material, such as, for example, a polymer to reduce friction. Needle 10 may also be subjected to a surface treatment to modify the external and/or internal surface of shaft 14.

[42] Needle 10 may be connected to an auto-injector or other medical device, such as, for example, diffusion devices, implantable fluid delivery devices, syringes, surgical devices, etc. Auto-injectors may include any type of injection device capable of automating part of the drug injection process. Further, auto-injectors may be disposable, reusable, configured to deliver a fixed volume dose, and/or configured to vary dose volume. Auto-injectors may be configured to deliver a range of drug volumes through a range of differently sized and configured needles.

Needle Design Parameters

[43] Needle 10 may be defined by one or more needle parameters 28. Needle parameters 28 may include any needle design information, such as, for example, needle length, needle gauge, bore diameter, tip configurations, side aperture locations, side aperture size, side aperture shape, side aperture cross section, needle materials, needle coatings, needle surfaces, needle connection geometries, etc. It is contemplated that needle 10 may be manufactured from a range of materials, such as, for example, metals, alloys, polymers, ceramics, etc. Needle 10 may include coatings and/or surface finishes. For example, coatings and/or surface finishes may reduce injection time, reduce pain associated with injection, prolong needle shelf-life, and/or improve needle structural properties.

[44] The location, configuration, shape and/or size of side apertures may be designed to significantly reduce the injection forces generated by movement of fluid through needle 10. For example, an auto-injector may be designed to operate with needle 10 to deliver 1 ml of fluid within ten seconds. Needle 10 may be a specific length to deposit the fluid at a certain depth beneath the skin and a certain size to minimize pain. Further, groups of side apertures 22 may be designed for use with a viscous fluid. For example, groups of side apertures 22 maybe shaped and/or sized to allow a flow rate of 0.1 ml/sec of a fluid of a specific viscosity using an auto-injector capable of exerting a specific injection force.

[45] Groups of side apertures 22 may be designed to allow a pre-defined fluid flow from needle 10 while maintaining the structure integrity of needle 10. For example, the length in the y-direction of side apertures may be limited by the material of shaft 14 and/or the diameter or bore 18. The length in the x-direction of side apertures may vary depending on needle parameters, fluid properties and injection parameters.

Computer Simulations

[46] Computational fluid dynamics simulations of a fluid injection process were developed to determine needle design and injection parameters. Simulation of the fluid injection process may include a grid-based model where one or more finite elements define a spatial domain of the injection equipment. An algorithm may be applied to solve the equations of motion, such as, for example, Navier-Stokes equations for viscid flow or Euler equations for inviscid flow. Additional modeling could be achieved by means known in the art, such as, for example, smoothed particle hydrodynamics, spectral methods or Lattice Boltzmann methods.

[47] The simulation may be used to determine needle design and/or injection parameters for a specific drug formulation. By modeling the injection process, the needle design and injection parameters may be modified to more accurately control the injection process. Injection parameters may include any parameter capable of describing a simulated fluid injection process. For example injection parameters may include injection forces, injection pressure, injection time, spring constant, side port flow rates, distal aperture flow rate, plunger velocity, etc. The simulation may require defining one or more needle parameters and one or more fluid parameters. Fluid parameters may include any fluid property and/or any computational means to model fluid flow. For example, fluid parameters may include viscosity, temperature, volume, velocity, density, mass, pressure, compressibility, Reynolds number, boundary layer conditions, etc. [48] A computational fluid dynamic (CFD) simulation of side ported needle 10 maybe created using appropriate CFD software. Computational representation of the needle may be created using computer aided design (CAD) software. For example, CAD software may include SolidWorks v.2000 (SolidWorks Inc., Concord, MA). Following formation of needle 10 geometry using CAD software, a dynamic computational mesh may be applied. The mesh can be used to perform numerical simulations to model the motion of the plunger as it moves down the syringe. Computational mesh software may include Gambit v. 2.1.6 and FLUENT v.6.1.22 (both from Fluent Inc., Lebanon, NH). The surrounding tissue may be modeled using appropriate pressure boundary conditions. Newtonian fluid properties may be assumed for the CFD simulation.

[49] The CFD simulation may use the dynamic mesh to model fluid flow. The dynamic mesh allows a single injection simulation to incorporate multiple plunger speeds. Fluid flow can be described by the Navier-Stokes equation of motion,

JL + v • Vv = -VP + //V²V dt ^μ

where p is the fluid density, μ is the viscosity, v is the velocity, and P is the pressure. The fluid is assumed incompressible, therefore V - V = O (mass conservation). The plunger motion may described by the dynamic mesh equations: d

I pφ dV + J pφ ( M - u _g ). d A = J r V φ .d A + £ S _φ dV where dt

p is the fluid density, u is the flow velocity vector, which are used to move the plunger at a known speed along the length of the syringe. To confirm the accuracy of the CFD simulation, experimental data was compared to simulated results. Simulated injection into tissue results in suitable spring force with an injection time of approximately 10-12 seconds. For equivalent needle designs and injection parameters, the simulated and experimental results varied by less than approximately 5%.

[50] Fig. 4 illustrates a flow rate profile from a CFD simulation of a 27G needle designed according to the present invention. The flow rate profile shows the percentage fluid flow from distal aperture 20, from two distal laterally aligned and opposed apertures 24a, 24b, and from two proximal laterally aligned and opposed apertures 26a, 26b of needle 10. hi Fig. 4, line 30 represents the flow rate of distal aperture 20, line 34 represents the flow rate of distal side apertures 24a, 24b, and line 32 represents the flow rate of proximal side apertures 26a, 26b. Fig. 4 shows the variation of flow rate profile and plunger velocity. The computer simulation models the flow rate profile resulting from the flow of 1 niL of fluid through needle 10.

[51] The computer simulations show that line 30, representing the flow rate of distal aperture 20, increases with increasing plunger velocity. These results indicate that as the plunger velocity increases, a larger percentage of fluid flows out of distal aperture 20. Line 32, representing the flow rate of proximal side apertures 26a, 26b, shows a general decrease in flow rate with decreasing plunger velocity. These results indicate that as plunger velocity increases, the percentage of fluid flowing out proximal side apertures 26a, 26b decreases. Line 34, representing the flow rate of distal side apertures 24a, 24b, shows an increasing and then decreasing percentage of flow rate with increasing plunger velocity. These results indicate that at plunger speeds below approximately 100 mm/min, the percentage of fluid exiting needle 10 via distal side apertures 24a, 24b increases with increasing plunger speed. As the plunger speed increases above approximately 100 mm/min, the percentage of fluid exiting needle 10 via distal side apertures 24a, 24b decreases with increasing plunger speed. To summarize these results, at high plunger velocities the majority of fluid flows through distal aperture 20, as indicated by line 30. In contrast, at low plunger velocities, the majority of fluid flows through proximal side apertures 26a, 26b, as indicated by line 32.

[52] The results shown in Fig. 4 indicate that fluid flow rates through distal aperture 20 and groups of side apertures 22 may not be uniform. The flow profiles further indicate that flow profiles are influenced by plunger velocity. For example, if the majority of fluid could flow through proximal side apertures 26a, 26b, a low plunger velocity could be used. Alternatively, if the majority of fluid could be delivered to distal side apertures 24a, 24b, a plunger velocity between approximately 70 and approximately 120 mm/min can be used. Increasing plunger velocity above approximately 120 mm/min can result in the majority of fluid exiting distal aperture 20.

[53] The movements of fluids of different viscosity were modeled using the computer simulations. Generally, increasing fluid viscosity resulted in flow profiles similar to those profiles shown in Fig. 4, where flow rate of distal aperture 20 increased with increasing plunger velocity and flow rate of proximal side apertures 26a, 26b decreased with increasing plunger velocity. The flow rate of distal side apertures 24a, 24b is similar to described above, increasing then decreasing with increasing plunger velocity. The main difference between flow profiles using fluids of different viscosity is the trend that fluids of higher viscosity cause a shift of flow profiles to higher plunger velocities. Specifically, modeling a fluid with a viscosity of water (i.e. 1 cP) resulted in the flow rate of distal aperture 20 increasing starting at plunger velocity approximately 40 mm/min, as indicated by line 30 shown in Fig. 4. If fluid viscosity is increased to approximately 4 cP, the flow rate of distal aperture starts increasing at plunger velocity approximately 60 mm/min and for fluid viscosity approximately 10 cP, flow rate of distal aperture 20 starts increasing at plunger velocity approximately 160 mm/min. These results show that increasing fluid viscosity widens the range of plunger speeds where fluid flows predominantly from proximal side apertures 26a, 26b. For example, computer simulations indicate that the injection of an approximately 10 cP fluid at plunger speed of approximately 600 mm/min will result in less than 10% of the fluid exiting distal aperture 20, while the remaining approximately 90% of the fluid will exit distal side apertures 24a, 24b and proximal side apertures 26a, 26b at approximately equal percentages.

[54] Different drug formulations may require delivery to different regions within the dermis. Utilizing the results of Fig. 4, the plunger velocity of an auto-injector may be adjusted to achieve fluid delivery to a desired region within the dermis and/or in a predetermined fluid delivery profile. For example, it may be desirable to deliver a drug formulation at approximately the same flow rate percentages through distal aperture 20, distal side apertures 24a, 24b and proximal side apertures 26a, 26b. Such a delivery profile may be achieved by selecting an appropriate plunger velocity. For example, the results of Fig. 4 show that such a uniform flow profile may be achieved with plunger velocities between approximately 60 and approximately 120 mm/min. It is also contemplated that pain may be minimized by appropriate selection of fluid flow profiles from distal aperture 20, distal side apertures 24a, 24b and proximal side apertures 26a, 26b. For example, pain may be reduced by reducing the percentage of fluid flowing through distal aperture 20, which may be accomplished by utilizing lower plunger velocities as shown in Fig. 4.

[55] The computer simulation was used to compare the injection pressures generated using conventional standard needles containing no side ports and needles containing side ports, according to the present invention. The simulation modeled fluid flow from needles into air, and plunger speed was set to approximately 360 rnm/min. Standard needle developed a maximum injection pressure of approximately 1.85 x10⁵ P a. A side ported needle under equivalent conditions developed a maximum injection pressure of approximately 1.35 xlO⁵ Pa. The injection pressure of side ported needle was approximately 27% less than the injection pressure of a standard needle containing no side ports.

[56] The computer simulation compared the injection pressures generated using side ported needles at different plunger velocities. If plunger velocity was reduced from approximately 360 to approximately 180 rnrn/min, the injection pressure generated reduced from approximately 1.35 xlO⁵ to approximately 0.55 xlO⁵ Pa (approximately 59% reduction). Therefore as the plunger velocity decreases, the injection pressures generated also decrease.

[57] The computer simulations modeled injection pressures when the needle was located in tissue versus air. Side ported needles according to the present invention and conventional standard needles were compared in tissue at plunger speed of approximately 360 mm/min. The results of the computer simulations showed an approximate 45% decrease in injection pressure with the side ported needle compared to the standard needle. For plunger speed of approximately 180 mm/min, there was an approximate 57% decrease in injection pressure with the side ported needle compared to the standard needle.

[58] The affect of fluid viscosity on injection pressure was modeled using the computer simulations. The injection of fluids of viscosity approximately 4 and approximately 10 cP into standard and side ported needles were modeled for approximately 360 mm/min plunger speed. The injection simulation using approximately 4 cP fluid showed an approximate 32% decrease in injection pressure between the side ported needle compared to the standard needle. The injection simulation using approximately 10 cP fluid showed an approximate 29% decrease in injection pressure between the side ported needle compared to the standard needle.

[59] To summarize the results of the computer simulations comparing injection pressures between standard (i.e., non-side ported) and side ported needles, side ported needles generate significantly lower injection pressures than standard needles. Generally as plunger velocity increases the fluid flowing through distal aperture 20 also increases. Therefore at higher plunger velocities, the effect of groups of side apertures 22 would be expected to be reduced as the majority of fluid flows through distal aperture 20. However, at high plunger velocities, such as, for example, approximately 360 mm/min, a side ported needle generates an injection pressure approximately 27% lower than a standard needle. As the plunger velocity decreases, and the percentage of fluid flowing through groups of side apertures 22 increases, and the influence of side apertures on injection pressure is more pronounced. For example as plunger velocity decreases from approximately 360 to approximately 180 mm/min, there is a corresponding injection pressure reduction of approximately 59%.

[60] • Groups of side apertures 22 further reduced injection pressure when modeling injections into body tissue. Instead of the approximately 27% reduction in injection pressure at approximately 360 mm/min that occurred in air, there was an approximate 45% reduction in injection pressure when the injection was modeled in tissue. Therefore side ported needles are more effective than standard needles at reducing injection forces when fluid is injected into tissue as compared to air. In addition, injection pressure is further reduced when plunger velocities are decreased, and the fluid flowing through side apertures increases. For example at a plunger speed of approximately 180 mm/min, there was an approximate 57% decrease in injection pressure developed by the side ported needle compared to the standard needle. Lower injection pressures may reduce injection time, spring constant and/or size of auto-injector.

[61] Figs. 5 and 6 show flow profile distributions for 23 G and 27G side ported needles with plunger velocities of approximately 102 mm/min and approximately 360 mm/min, respectively. The flow profiles include the fluid flow from distal aperture 20, distal side apertures 24a, 24b and proximal side apertures 26a, 26b of needle 10. Specifically, bars 36a, 36b, 36c, and 36d represent flow from distal aperture 20, bars 38a, 38b, 38c, and 38d represent flow from proximal side apertures 26a, 26b and bars 40a, 40b, 40c, and 4Od represent flow from distal side apertures 24a, 24b in Figs. 5 and 6. Figs. 5 and 6 show that variations of plunger velocity and needle gauge can affect the resulting flow profile distributions.

[62] Figs. 5 and 6 show the effect of needle gauge on flow profile distribution.

Generally, a higher needle gauge (i.e. smaller diameter) shows a greater percentage of fluid flow through distal aperture 20. This trend is indicated by the increase of distal aperture flow 36d compared to distal aperture flow 36c, and distal aperture flow 36b compared to distal aperture flow 36a. Generally, a lower needle gauge (i.e. larger diameter) shows a greater percentage of fluid flow through groups of side apertures 22. This trend is indicated by the increase of proximal side apertures flow 38a and distal side apertures flow 40a (lower gauge) compared to proximal side apertures flow 38b and distal side port flow 40b (higher gauge). It is interesting to note that decreasing needle gauge from 27 to 23 (i.e. increasing needle diameter) for a plunger apertures of approximately 102 mm/min results in a dramatic increase in the fluid flow through proximal side apertures 26a, 26b. The results of Fig. 5 show a dramatic increase in the fluid flow through proximal side apertures 26a, 26b for a needle of 23 gauge compared to 27 gauge, as indicated by the flow profile represented by bars 38c and 38d respectively. The increase in fluid flow through proximal side apertures 26a, 26b is accompanied by a substantial decrease in fluid flow through distal side apertures 24a, 24b and distal aperture 20. The substantial decrease in fluid flow is shown by comparing bars 4Od and 40c, representing fluid flow from distal side apertures 24a, 24b and bars 36d and 36c, representing fluid flow from distal aperture 20. It may therefore be possible design a needle without distal aperture 20 and/or distal side apertures 24a, 24b, and still maintain sufficient fluid flow through proximal side apertures 26a, 26b.

[63] The results shown in Figs. 5 and 6 indicate that faster plunger velocity and high needle gauge result in the majority of fluid exiting distal aperture 20, as shown by the flow profile indicated by 36b, 38b, and 40b. Li contrast, lower plunger velocity and lower needle gauge result in the majority of fluid exiting proximal side apertures 26a, 26b, as shown by the flow profile indicated by 36c, 38c, and 40c. A more uniform flow profile results from a lower plunger velocity and higher needle gauge, as indicated by 36d, 38d, and 4Od. Therefore selection of specific plunger velocities and/or needle gauges may be used to create specific fluid flow profiles from needle 10. The design of needle 10 may also be modified to modify the flow profile from needle 10. For example, groups of side apertures 22 may be modified by number of apertures, size, shape, location, etc. Such modifications may be modeled rather than the more costly and time consuming option of building and testing unique prototype needles. Spring Force Selection

[64] A number of factors may affect the selection of a spring for an auto-injector.

For example, the selection factors may include drug volume, drug viscosity, needle gauge, number of side ports, injection time, material properties, subcutaneous or intramuscular injection, etc. The computer simulation may be used to model injection flow and select a suitable auto-injector spring.

[65] Table 1 shows the results of a computer simulation modeling the injection of fluids of approximately 1 mL volume and viscosities of approximately 1 cP, approximately 2 cP, and approximately 4 cP. The simulation used two needle designs, one standard design with no side ports, and the other a needle including side ports according to the present invention. Standard and side ported needles of 27 gauge were modeled with approximately 5.33 sec injection time and plunger velocity of approximately 360 mni/min. The simulation was conducted using needles in air and in tissue. The tissue environment modeling incorporated non-zero boundary conditions. Spring constants (in kg) for the various conditions were then determined, as shown in Table 1. Table 1.

[66] The results shown in Table 1 indicate that the addition of groups of side apertures 22 (i.e., "Side Ports") can decrease the spring constant by about 26% when injecting fluids of varying viscosity into air. In comparison, the addition of groups of side apertures 22 can decreases the spring constant by about 44% when injecting fluids of varying viscosity into tissue. These results indicate that for fluids of varying viscosity, auto-injectors using side ported needles may use lower spring constants than auto-injectors using standard needles.

[67] It will be apparent to those skilled in the art that various modifications and variations can be made in the system of the present invention and in construction of the system without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only.

Claims

ClaimsWhat is claimed is:

1. A needle for delivering a fluid to a body, comprising; a shaft having a proximal end, a distal end, and a hollow bore that extends from the proximal end to the distal end; the proximal end being configured to place a fluid reservoir in fluid communication with the hollow bore, the distal end being configured to penetrate the body; and at least two groups of side apertures in the shaft, wherein each group of side apertures includes at least two laterally aligned side apertures configured to permit fluid communication between the hollow bore and an exterior of the shaft.

2. The needle of claim 1, wherein, in at least one of the groups of side apertures, the at least two laterally aligned side apertures are spaced approximately equidistant around a circumference of the shaft.

3. The needle of claim 1, wherein, in at least one of the groups of side apertures, a size of a first side aperture is substantially the same as a size of a second side aperture.

4. The needle of claim 1, wherein, in at least one of the groups of side apertures, a shape of a first side aperture is substantially the same as a shape of a second side aperture.

5. The needle of claim 1, wherein, in at least one of the groups of side apertures, a ratio of a lateral dimension to a longitudinal dimension of the at least two laterally aligned side apertures is between approximately 1:2 and approximately 1:200.

6. The needle of claim 1, wherein the shaft has a gauge of between 18 and 33.

7. The needle of claim 6, wherein the shaft has a gauge of between 23 and 27.

8. The needle of claim 1, wherein the distal end of the shaft includes a distal end aperture.

9. The needle of claim 8, wherein a ratio of a sum of areas of the at least two groups of side apertures to an area of the distal end aperture is greater than 5:1.

10. The needle o f claim 1 , wherein the needle forms a portion of a fluid delivery device configured to deliver the fluid to the body.

11. The needle of claim 10, wherein the at least two groups of side apertures are configured to reduce the force needed to deliver the fluid via the fluid delivery device.

12. The needle of claim 10, wherein the fluid delivery device includes a spring to actuate a structure configured to deliver fluid from the needle.

13. The needle of claim 12, wherein the needle and the spring are configured to cooperate to permit a percentage of a fluid to flow through the at least two groups of side apertures.

14. The needle of claim 10, wherein the fluid delivery device is selected from the group consisting of an auto-injector, a pen injector, a syringe, an infusion device, and an implantable device.

15. The needle of claim 14, wherein the syringe is at least partially formed from either glass or plastic.

16. The needle of claim 1, wherein one of the at least two groups of side apertures is a proximal group of side apertures.

17. The needle of claim 16, wherein the proximal group of side apertures is positioned at least about 4.5 mm from the proximal end of the shaft.

18. The needle of claim 1, wherein one of the at least two groups of side apertures is a distal group of side apertures.

19. The needle of claim 1, wherein one of the at least two groups of side apertures is positioned on a distal portion of the shaft and one of the at least two groups of side apertures is positioned on a proximal portion of the shaft.

20. The needle of claim 1, wherein at least one of the at least two groups of side apertures includes at least three laterally aligned side apertures.

21. An injection needle for sub-dermal delivery of a fluid to a body, comprising; a shaft having a proximal end, a distal end, and a hollow bore extending from the proximal end to the distal end; the proximal end being configured to place a fluid reservoir in fluid communication with the hollow bore, the distal end being configured to penetrate the body; and at least one group of side apertures in the shaft, the at least one group of side apertures being positioned at least approximately 4.5 mm from the proximal end of the shaft to permit sub-dermal delivery of the fluid to the body, the at least one group of side apertures including at least two laterally aligned side apertures configured to permit fluid communication between the hollow bore and an exterior of the shaft.

22. The needle of claim 21, wherein, in at least one group of side apertures, the at least two laterally aligned side apertures are spaced approximately equidistant around a circumference of the shaft.

23. The needle of claim 21, wherein, in at least one group of side apertures, a size of a first side aperture is substantially the same as a size of a second side aperture.

24. The needle of claim 21, wherein, in at least one group of side apertures, a shape of a first side aperture is substantially the same as a shape of a second side aperture.

25. The needle of claim 21, wherein, in at least one group of side apertures, a ratio of a lateral dimension to a longitudinal dimension of the at least two laterally aligned side apertures is between approximately 1:2 and approximately 1:200.

26. The needle of claim 21, wherein the shaft has a gauge of between 18 and 33.

27. The needle of claim 26, wherein the shaft has a gauge of between 23 and 27.

28. The needle of claim 21, wherein the distal end of the shaft includes a distal end aperture.

29. The needle of claim 28, wherein a ratio of a sum of areas of the at least one group of side apertures to an area of the distal end aperture is greater than 5:1.

30. The needle of claim 21, wherein the needle forms a portion of a fluid delivery device configured to deliver the fluid to the body.

31. The needle of claim 30, wherein the at least one group of side apertures is configured to reduce the force needed to deliver the fluid via the fluid delivery device.

32. The needle of claim 30, wherein the fluid delivery device includes a spring to actuate a structure configured to deliver fluid from the needle.

33. The needle of claim 32, wherein the needle and the spring are configured to cooperate to permit a percentage of a fluid to flow through the at least one group of side apertures.

34. The needle of claim 30, wherein the fluid delivery device is selected from the group consisting of an auto-injector, a pen injector, a syringe, an infusion device, and an implantable device.

35. The needle of claim 34, wherein the syringe is at least partially formed from either glass or plastic.

36. The needle of claim 21, wherein the at least one group of side apertures includes at least three laterally aligned side apertures.

37. A method for determining a parameter of a fluid delivery device, the method comprising the steps of: creating a computational representation of the needle to be tested; applying a computational mesh to the computational representation of the needle to be tested; modeling fluid flow using one or more fluid parameters; and determining at least one of an injection parameter or a needle parameter of the fluid delivery device.

38. The method of claim 37, wherein the needle to be tested includes at least one group of side apertures positioned along a length of the needle to be tested, the at least one group of side apertures including at least two laterally aligned side apertures.

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39. The method of claim 37, wherein the computational representation includes a computer aided design representation.

40. The method of claim 37, wherein modeling fluid flow includes applying a Navier-Stokes equation.

41. The method of claim 37, wherein the fluid parameter is selected from the group consisting of viscosity, temperature, volume, velocity, density, mass, pressure, compressibility, and Reynolds number.

42. The method of claim 37, wherein the injection parameter is selected from the group consisting of injection force, injection pressure, injection time, spring constant, side aperture flow rate, distal aperture flow rate, and plunger velocity.

43. The method of claim 37, wherein the needle parameter is selected from the group consisting of length, gauge, bore diameter, tip configurations, side aperture locations, side aperture size, side aperture shape, materials, coatings, surfaces, and connection geometries.