Injection pumpTechnical Field
The present invention relates to an injection pump.
Background
One of the main fields of application of such pumps is the injection of physiologically active fluids into patients and/or the removal of body fluids for diagnostic purposes. For such use, these pumps are typically equipped with a contact surface for attachment to the skin of a patient and a cannula for accessing patient tissue or blood vessels for introducing injection fluid or withdrawing analysis fluid.
Injection devices are widely used in patient treatment, but their size and complexity greatly limit their application to specialized equipment. More recently, ambulatory use of injection devices has been advocated in the treatment of diabetes for the delivery of insulin. To achieve the necessary precision of delivery, these injection devices typically use syringe pumps. The size of these devices is considerable (this is mainly represented by the extended, longitudinal shape of the filling syringe with the pull-out piston) and requires their outer sleeve component to be attached to e.g. a tape or lining component and they operate together with the connector barrel to place the cannula subcutaneously, which leads to inconvenience and safety issues.
Recently, due to these drawbacks, infusion devices have been proposed that can be attached directly to the skin, preferably without a long barrel connected to a subcutaneous delivery cannula. Accurate syringe pumps with sufficient volume for injection of fluid are difficult to use for direct attachment to the skin due to the necessary reduction in size and weight. Therefore, alternative pump types with many drawbacks in delivery accuracy and reliability have incorporated piston pumps utilizing valves, or by squeezing flexible containers, under very varying environmental and physiological conditions encountered in real-life operations (e.g., delivery from reservoirs with peristaltic pumps). Syringe pumps for this purpose have a barrel with a large diameter in order to avoid an elongated longitudinal footprint, but this solution has the disadvantage that a high driving force is required to inject against a considerable tissue back pressure, most importantly because of the risk of air bubbles entering and blocking the injection cannula due to the almost inevitably rather large dead volume, and the unwanted rather large bolus injection due to the stick-slip effect.
An attractive solution to reduce the footprint of a syringe pump with a suitably narrow barrel is to use an arcuate barrel as described, for example, by m.p. loeb and a.m. olson in us patent 4,525,164 filed 1981. Although this concept is attractive for precision patch infusion pumps, it is not obvious to switch to a safe and cost effective medical product, since manufacturing such a ring syringe pump with the necessary performance at a reasonable cost presents considerable implementation difficulties. Obviously, for the production of curved tubes, these products must use plastic technology with an inherent significant tolerance margin due to the difference in shrinkage. Since, for example, the core of the injection molding tool has to be removed by a rotational movement and then the proximal and distal walls of the torus differ in terms of shrinkage, the resulting deviations from the ideal circular shape cannot be easily corrected by adapting the respective tool. The almost inevitable deviations of the manufactured torus from the ideal circular shape and the deformation under the large forces necessary to overcome the high tissue back pressure cause problems due to the imperfect fit between the arc-shaped part of the cylinder and the rotational movement of the rigid arc-shaped driving rod of the piston, i.e. to achieve an adequate seal with the piston with reasonable friction and to avoid sticking. These difficulties become even more severe in the case of small barrel diameters, such as are required for precision syringe pumps for delivering insulin. Although there have recently been several descriptions of arcuate syringe pumps, such as described by r.paul mount et al in WO 2008/024812 a2 or by o.yodfad et al in WO 2008/139458 a2, this problem has not been adequately addressed and no obvious embodiment has been found from these descriptions or figures.
Disclosure of Invention
It is an object of the present invention to provide an arcuate syringe pump which avoids the disadvantages of the prior art devices.
The use of a curved annular barrel configuration combines the high precision of the syringe pump with a compact shape. In order to achieve an optimal fit between the cylinder and the piston throughout the movement of the piston along the axis of the cylinder, the piston drive rod is guided and supported by the surface of the inner cylinder wall and is preferably flexible, thus self-adapting to the inner curvature of the cylinder. The cartridge has a curvature preferably having an arc of 180 ° or less, with 150 ° -160 ° being most preferred for the optimum length/diameter ratio of the cartridge for precise dosing, and the cartridge can be manufactured by standard plastics techniques. Furthermore, with the improved individual elements of the device and the cooperation of these elements, the desired reduction in overall dimensions and simplification of the mechanical operation are achieved. The main problem of the current device is solved according to the present invention by an injection or analytical fluid extraction device having the features disclosed herein (below).
The subject injection device for introducing injection fluid into a patient through the skin of the patient or through an intravenous or intraperitoneal port comprises an injection pump having a barrel in the form of an annular tube segment and a piston tightly mounted within the barrel, the piston being actuatable by a driver and control means to pass through the entire barrel. The drive rod, guided and supported by the inner wall of the barrel, moves the piston, and the piston is preferably flexible and thus self-adapting to the curved portion of the barrel without the risk of sticking due to imperfect cooperation between the curved portion of the barrel and the curved portion of the rigid drive rod of the piston. Further, such a configuration may be adapted to deliver fluid by pushing the piston with the rod guided by the distal inner surface of the barrel and to withdraw fluid by pulling the piston with the rod guided by the proximal inner surface of the barrel. The device has a contact surface or intravenous port for contacting the skin of a patient. Typically, the skin-contacting contact surface is coated with an adhesive, and a syringe pump is connected to a cannula having a tip configured and dimensioned to pierce the skin of a patient or a septum of a port and introduce an injection fluid into the patient or withdraw an analysis fluid.
In a preferred embodiment, the device of the present invention has a cannula that is fixedly positioned relative to the housing and relative to the infusion pump. The insertion mechanism of the cannula, which is inserted into the skin of the patient, preferably comprises a flexible contact surface which is adhered to the skin.
As used herein, the following definitions define the terms:
the adhesive contact surface for temporary covering on the skin is made of a material with strong adhesive properties, extensibility and minimal allergenicity. The adhesive layer is fixed to the bottom of the device, covering the entire surface or at least its central part leaving free edges so as not to interfere with its flexibility. Preferably, the surface of the adhesive layer that is fixed to the skin is significantly larger than the surface of the flexible base (leaving an edge that is not fixed to the flexible base) to which it is fixed to the device. This can be done by: for example by the adhesive layer extending beyond the surface of the bottom of the device or preferably by using an adhesive surface that adheres to the skin, shaped like or only slightly larger than the surface of the flexible surface of the device, but fixed to the flexible surface of the device so that the outer annular area is not fixed to the bottom of the device. Such a design (medical device with rigid bottom) is described in EP 0825882.
The analyte fluid is blood, interstitial fluid or dialysate that is in contact with interstitial fluid through a semi-permeable membrane.
An analyte refers to any endogenous or exogenous substance whose concentration can be used to diagnose health, organ function, metabolic state, or the ability of an individual to metabolize a drug. Examples of endogenous substances are glucose, milk, oxygen, creatinine, etc. Examples of exogenous substances are drugs, metabolites of these drugs, diagnostic substances (e.g. inulin), etc.
The element with a flexible surface is composed of a housing, preferably with a circular or oblong footprint and with a flexible bottom. The base plate is configured such that it can be deformed into a convex shape with a convex portion, such as a cone or a gable portion (position 1). Another feature of the base is that it can be abruptly changed from a convex shape to a flat shape (position 2) with sufficient speed and force that this motion can provide the driving energy for implanting the implantable component of the injection cannula or diagnostic probe by pulling the skin attached by the adhesive surface against the tip of the cannula or diagnostic probe. Such a flexible surface can be obtained by having suitable segments of the surface acting as articulation zone of the spring and/or by using an elastic material with the necessary recovery stretch properties, which moves for example from a pre-stressed shape to assume a flat relaxed shape.
The means for positioning the flexible surface in two well-defined positions in relation to the implantable part of the injection cannula or diagnostic probe consist of an element that causes the flexible surface to deform to a convex pre-stressed shape and allows a quick release from this position into a flat relaxed shape that the entire surface takes on in harmony. This can preferably be achieved by a number of pin-shaped elements protruding from the flexible surface and pushing onto the sliding bolt mechanism, but other configurations using screws, ramps, levers, etc. are also possible.
Such elements with flexible surfaces can be manufactured by injection moulding of a suitable plastic, but also by using other materials, such as steel, composites or ceramic materials etc. The bottom of the element has an opening in the form of a hole or cut-out to serve as an opening for an implantable part of an injection cannula or diagnostic probe. The implantable parts of the injection cannula or diagnostic probe are axially positioned relative to the base such that in position 1 they are completely covered and in position 2 they protrude from the base.
Delivery of injection fluids includes relatively rapid injection (bolus) and relatively slow introduction (also known as infusion or instillation) of a liquid into the body.
The diagnostic probe is a functional element for determining the concentration of an analyte and represents, but is not limited to, any withdrawn analysis fluid and online analysis or sampling system. In the case of microdialysis systems, the dialysis membrane forms an interface between interstitial fluid and the dialysis fluid passing through the other side of the membrane. In a preferred embodiment, the microdialysis probe is composed of an outer and an inner barrel, which at the implantable tip is covered by a dialysis membrane. The inner cartridge is connected to a pump for delivering the dialysis fluid and the outer cartridge is connected to an analysis or sampling system.
The drive and control means contain all the necessary mechanical, electronic and software elements for all the necessary functions of a similar device, but are not limited to moving the piston of the ring syringe pump according to internal or external signals, starting, controlling and checking the correct function of the device, supplying and controlling diagnostic elements and converting sensor signals into analyte measurements, storing, displaying and delivering the analyte measurements online or in batches, interacting with external control means (preferably wirelessly), and issuing warning signals if the device is not functioning properly or if the analyte measurements are not within a predetermined range.
The drive rod of the piston has a structure that provides sufficient radial and axial flexibility to adapt to the actual curvature and axial position of the annular cylinder but exerts sufficient rigidity in the tangential direction to enable precise movement of the piston within the cylinder. Preferably, the drive rod is flexible and its given form closely corresponds to the arc-shaped part of the annular cylinder and is manufactured using a suitable plastic material in order to achieve an almost perfect fit with the actual form of the inner surface of the cylinder with small radial forces. The adaptation of the drive rod to the actual curved portion and the axial position of the annular cylinder avoids the possibility of harmful blocking due to imperfect cooperation between the axis of the cylinder and the axis of the rigid drive rod.
The flexible drive rod usually has a contact support allowing low-friction contact with the inner surface of the cylinder wall in its middle plane and a toothed rack which meshes with a cogwheel of the drive means. The low friction contact between the holder and the inner surface of the wall of the cylinder is achieved by suitable forms and materials.
The bracket can be an integral part of the drive rod or attached thereto, allowing the use of different materials with improved sliding properties and obtaining the necessary radial and axial flexibility of the drive rod, the bracket can for example have a segmented structure.
Another preferred configuration replaces sliding contact with rolling contact with the inner surface of the cartridge wall. Such a construction can for example have a number of rollers which are connected at the hinge region carrying the roller shaft by segments having sufficient flexibility to adapt to the curvature of the drum.
The contact brackets absorb all the radial force components, protecting the piston seal from these forces, which cause significant seal deformation, problems of tightness and stick-slip phenomena due to imperfect cooperation between the axis of the cylinder and the axis of the rigid driving rod, up to piston blocking.
Typically, at one end of the drive rod, an end part in the form of a cross section of the cylinder but with a slightly smaller diameter is rigidly connected, forming a face orthogonally centred by the bracket with respect to the cross section of the cylinder, and transmitting the drive force from the drive rod to the piston sealed in tangential direction with respect to the axis of the cylinder. The piston with its seal (e.g., an O or X-ring) is welded to or attached to the end member, movably allowing the piston to self-locate centrally within the barrel. This can be achieved by a low friction sliding surface between the end member of the drive rod and the piston or by balls rolling on the interface and reduces problems that may arise from variations in the internal diameter of the barrel along its axis.
The functional package is designed to hold the rigid components of the device by a releasable connection mechanism and has a removable cap to protect the active surface of the diagnostic probe during storage in a confined environment (such as moisture) while allowing sterility to be maintained. The functional bag also has edge elements to allow proper attachment of the edges of the adhesive layer by pressing against the skin after removal of the cap. Furthermore, the feature pack protects the release/activation mechanism of the device from premature, undesired operation and the release/activation mechanism can only be activated after the device is attached to the skin and the feature pack is removed.
An intravenous port includes a catheter placed into a blood vessel and having a connecting element, preferably a septum at the outer end of the catheter.
A sampling device is a functional element for collecting an analytical fluid sample for the determination of analytes external to the device by, but not limited to, biochemical, immunological, HPLC or LC/MS methods. The sample can be collected in separate containers or in a continuous chamber, such as a cartridge or tube, taking care that: the mixing of samples obtained at different times is minimized. This can be achieved, for example, by introducing air segments or fluid segments that do not mix readily into the analytical fluid, forming separate samples within successive chambers.
The sliding bolt mechanism is adapted continuously to a plurality of fixed positions in a circular or linear movement and consists of an element (e.g. a solid surface or a hole) which shows a closed or open state. The movement of such a sliding mechanism is manually driven or driven, for example, by a spring actuated by a release element, for example, by depressing or releasing a button or handle, or by a rotational movement. In order to insert the fluid delivery cannula and the flexible sensor within the lead in parallel into the skin by means of the element having the flexible surface attached to the skin, movement of the sliding bolt mechanism from the storage position (position 1) to the next position (position 2) actuates a quick release of the flexible surface from the pre-stressed shape to assume a flattened, relaxed shape and inserts the fluid delivery cannula and the sensor lead into the skin when easy to operate. The temporary block of the sliding bolt mechanism in position 2 is now released and allows actuating the sliding bolt mechanism to move to the next position (position 3), which actuates the partial retraction of the guide pin.
Drawings
Preferred embodiments of the present invention are described below with reference to the accompanying drawings, in which:
fig. 1 is a schematic cross-sectional top view of an injection device having a circular syringe pump illustrating the principle of the circular syringe pumps of the prior art construction, but with a modification allowing a limited adaptation of the piston to the curved portion of the barrel.
Fig. 2 is a schematic cross-sectional top view of a combined injection and analysis fluid extraction device having two circular syringe pumps, according to an embodiment of the present invention.
FIG. 3 is a cross-sectional view of an injection filling component and an insertion mechanism of an injection cannula inserted into the skin according to one embodiment of the present invention.
Detailed Description
The injection device shown in fig. 1 has a housing with a cylindrical side wall 1, the cylindrical side wall 1 accommodating a cartridge in the form of a segment of an annular tube 2. One end 3 of the barrel is provided with a connection channel to a cannula (not shown). The cartridge has a circular cross-section.
The piston 4 is arranged in the interior of the barrel and is provided with a seal that fits closely at the inner wall of the barrel. The piston is connected to a drive rod 6, the drive rod 6 being circular in shape for driving the piston through the entire length of the barrel.
The fitting between the curved portion of the circular cylinder and the driving rod of the piston will be imperfect using the prior art for manufacturing circular cylinders. To remedy this problem, the mechanism 5 disclosed herein, which connects the piston to the rod 6, provides an improvement in the radial fit of the piston over prior art solutions (as described in us patent 4,525,164 by m.p. loeb and a.m. olson), because this structure has inherent problems of sealing and friction, using a resilient spherical piston that is slidably contacted by the cupped distal end of the drive rod, allowing it to rotate within the barrel.
At its end opposite the piston, the drive rod has a vertically curved arm 7 extending to the central pivot, reducing the radial component of the force and the friction generated by moving the piston through the barrel. The inside of the rod has a gear rim 8, which is driven by a gear drive 9. The gear drive is driven, for example, by a gear train and an electric motor (e.g., a watch mechanism drive), which can be regulated by signals from a built-in and/or remote control element (not shown in the figures) for controlled delivery. Alternatively, other drivers as known in the art can be used.
Using standard annular barrel manufacturing techniques, such as plastic techniques with injection molding tools having cores that must be removed by a rotational movement, deviations from a perfectly circular shape and variations in its shape are inevitable due to, for example, inherent differences in the shrinkage of the proximal and distal portions of the annular wall during manufacture. Because of this almost unavoidable deviation of the manufactured torus from the ideal circular shape, a precise geometric fit between the cylinder and the drive rod of the piston which is moved by the rotary motion cannot be ensured. Although the drive rod of the piston is manufactured using steel technology with a high degree of form stability, the fit of the attached piston to the shape of the barrel along its longitudinal axis varies. In fact, for example, a difference of only 2% between the radius of the barrel and the radius of the drive rod causes a severe relative displacement, which can lead to collisions between the barrel wall and the drive rod over an arc-shaped portion of a torus of, for example, 150 ° -160 ° (which can be manufactured with standard techniques and aims at substantially reducing the space occupied by the syringe pump). Furthermore, the plastic parts commonly used to make the housing of the retention cartridge and the guide rails of the drive rod are not absolutely rigid and can deform slightly, in particular under the action of the applied forces necessary to provide a pressure of several bars to overcome the tissue resistance. Due to the rigid drive rod (which is used in the previously described arc-shaped piston drive mechanism), the radial and axial forces generated to correct for the difference in actual shape between the drive rod and the axis of the barrel can be very large. These forces must be absorbed by the piston seal, causing it to deform, causing high friction, producing stick-slip phenomena until problems of blocking and/or tightness of the piston occur. Although the piston can be slightly adapted to correct the deviation between the axis of the cylinder and the axis of the driving rod, as described in the prior art and with the improvements discussed and exemplified in fig. 1, the worst case of blocking by clamping between the rigid driving rod and the cylinder wall cannot be excluded. Therefore, controlled and precise fluid delivery structures according to the prior art (in which a drive mechanism having a rigid drive rod is used to move the piston in the arced barrel) are not sufficiently safe for medical use. These problems are even more pronounced with the small diameter cartridges required for syringe pumps intended for accurate delivery of small volumes (e.g. insulin from diabetic patients).
According to the invention, a solution to avoid the stick-slip phenomenon and/or the tightness or even the blockage of the piston or the problem of clamping between the rigid driving rod and the wall of the cylinder is to use a driving rod of the piston adapted to the actual curvature of the cylinder, which is guided and supported by the inner wall of the cylinder. In contrast to the configurations described in the prior art, the rods guided and supported by the inner wall of the cartridge of the invention can adapt to all deviations in ideal shape and geometry that are inevitable due to the use of cost-effective manufacturing techniques and materials. In fig. 2, a preferred embodiment of the invention is illustrated, which can be adapted for delivering and withdrawing fluids.
Fig. 2 shows a combined injection and analysis fluid removal device with two separate circular injection pumps in a top view in horizontal section. The pump for delivering the injection fluid is shown in the more peripheral part of the figure, while the pump for withdrawing the analysis fluid is shown in the more central part. In fig. 2 parts corresponding to those of fig. 1 are given the same reference numerals. The embodiment of fig. 2 does not have a rigid drive rod. Instead, the driving rod 6 of the piston is formed so that its movement is guided and supported by the inner surface of the cylinder wall, as shown in cross-section in detail a. Importantly, the form and material optimized holder 11, even for taking advantage of low friction motion to increase accuracy and reduce the force necessary for piston motion, creates a sliding area between the drive rod of the piston and the inner surface of the cylinder wall. This can be achieved by using a drive rod plastic with suitable sliding properties or by attaching edges of a suitable material (e.g. steel wire), but other possibilities of friction reduction, such as a structure with many rollers (the axles of which are held by brackets) can be achieved to avoid and replace the sliding resistance by rolling resistance.
The radial and axial flexibility of the drive rod exemplarily shown in detail a is further increased, for example by using a segmented structure of a carriage slidingly holding wires or rollers or even a spine-like structure of a flexible drive rod with segments coupled by articulation zones. In order to ensure a safe transmission of power to the gear rim 8 for moving the piston, the gear drive 9 is supported by diametrically opposite brackets 10, which brackets 10 preferably take the form of anti-friction bearings, pressing against contact edges 11 of the drive rods, but other constructions, such as attachment to the side walls of the housing, are also possible.
The piston 4 with its seal (e.g. an O-or X-ring) is held by the holder of the drive rod at a defined distance from the inner surface of the cylinder wall and only transmits the tangential driving force to the piston. Furthermore, in order to achieve self-centering of the piston in the cavity of the cylinder, in an alternative construction, the piston is not rigidly welded directly to the end of the drive rod, but is movably attached to an end part of the drive rod (which is held by the bracket at a defined distance from the cylinder wall). This can be achieved, for example, by low friction sliding surface contact between the end piece of the drive rod and the piston or by a ball rolling at the interface. Such a self-centering structure can be useful to improve pump performance in the event that an efficient manufacturing process results in a barrel that varies in internal shape and diameter along its axis.
For delivery of injection fluid, the drive rod of the piston is pushed while guided and supported by the distal inner surface of the barrel (shown in detail a). In contrast, a circular syringe pump for withdrawing the analysis fluid operates in the suction mode, and the drive rod of the piston is pulled and guided and supported by the proximal inner surface of the barrel (mirror image of detail a, not shown as detail). A proximally located gear rim 8 moving the piston can also be used, for example, in a configuration where the gear rim is double-tracked and is correspondingly returned to the bracket 11, and the gear drive 9 has a cut-out to accommodate the protruding bracket.
Figure 3 is the central part of the device cut tangentially through the end 3 of the cartridge. The first channel 15 opens to the upper side of the device and is closed by the membrane 14. For filling the cartridge with injection fluid, a syringe (not shown) with a needle 13 is caused to pierce the septum 14. Prior to filling, the piston contacts the end 3 of the barrel (not shown). Injection fluid is introduced through the channel 15, pushing the piston towards the other end of the barrel.
A second channel 17 leads from the interior of the barrel 2 to the injection cannula 16 for delivering injection fluid into the skin. Cannula 16 is closed at the other end with a septum seal 18 held in a housing 19. The overall structure is arranged so that the dead volume is minimal and there is no significant volume of air in the system after filling with injection fluid.
In this exemplary embodiment, the skin-inserting insertion device of the cannula 16 has a flexible base plate 20 attached to the skin by an adhesive layer 21. In the standby mode shown in the figures, the flexible base plate is deformed into a convex shape covering the cannula 16. The base plate is preferably annular or oblong and is preferably made up of two segments with diagnostic cuts that form a triangular wall-like portion when bent, for insertion of a cannula away from the center of the device. This configuration also allows for the simultaneous use of the insertion device with more than one cannula positioned along the diagnostic incision, for example, if more than one infusion pump (for more than one infusion fluid) is used and/or for combination with a diagnostic probe inserted into the skin. By the spring-type mechanism, the cannula additionally penetrates the septum seal 18 before the cannula enters the skin. These segments are connected to the perimeter of the casing 1 by elastic hinge zones and are moreover preferably made of flexible material. Alternatively, for example, in the form of radial segments, preferably 5-8 segments are formed with spaces between them and a central opening that, if a cannula is placed near the center of the device, forms a cone when the center is bent.
On its underside, the flexible base plate has an annular or oblong adhesive layer for attaching the device to the skin of a patient, which has a diagnostic incision or a concentric central opening, respectively, similar to the base plate. The bonding layer is composed of three parts: glue for fixing to a flexible base, fabric providing the necessary flexibility and glue for fixing to the skin. Suitable materials with low allergenic potential are commercially available. The adhesive layer can have a larger perimeter than the device, but it can also have the same perimeter if the attachment to the base plate leaves an outer area that is not connected to the housing.
When released, e.g. by a pre-stressed base plate actuated by a sliding bolt mechanism (not shown), it relaxes rapidly to a flat shape towards the bottom of the housing of the device 1, pushing the housing 19 of the septum seal 18 and the cannula 16 pierces the septum seal 18 and the skin attached by the adhesive layer.
Various alternative embodiments will become apparent to the skilled artisan upon reading this specification. For example, a drive means for moving the piston, or an implantation mechanism for a cannula for delivering injection fluid into a patient (or for removing analysis fluid from a patient) can be achieved by a number of chemical, mechanical or electrical means. Furthermore, the device can accommodate a wide variety of diagnostic elements and control and measurement devices for online analysis or for analytical fluid sampling for removal of analytes.
The main advantage of the device with the annular infusion pump described above is that it reduces the footprint, whereby the patient can comfortably wear and operate, and at the same time the infusion pump has an inherently high precision. The problems inherent in the prior art exemplarily listed for such pumps (sealing, friction causing stick-slip phenomena, and even retardation caused by the lack of exact fit between the actual form of the arc-shaped cylinder and the actual form of the piston, which is inevitable in the manufacture of annular cylinders, and the use of standard cost-effective technical means) are solved by using a drive rod as piston driver, which is guided and supported by the inner wall of the cylinder, so as to be able to adapt to all deviations from the ideal shape and geometry. Another advantage is that there are no problems associated with the connection tube between the syringe pump and the cannula penetrating the skin. Furthermore, the device according to the invention has little dead volume, thus avoiding the complex mechanism of moving air out of the system during filling of the pump with injection fluid.