RU2674085C1 - Spring assisted drug delivery mechanism - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: device comprises a housing; a piston rod having a longitudinal axis, a distal end and a proximal end that is axially movable in a distal direction relative to the housing, a mid-body fixed inside of the housing and coupled to the piston rod in such a manner that the piston rod is axially movable in a distal direction relative to the mid-body. Preloaded spring is operatively coupled to the piston rod in such a manner that the spring is released and the stored force in the spring supports driving the piston rod in the distal direction during a dose administration step. Preloaded spring is operatively coupled between the mid-body and the piston rod, and the preloaded spring is operatively coupled between the mid-body and a bearing of the piston rod.

EFFECT: invention relates to medical equipment, specifically to spring assisted drug delivery devices.

13 cl, 9 dwg

Description

Technical field

The present invention generally relates to injection devices such as a pen-type syringe and, in particular, dosage mechanisms for such drug delivery devices. Such devices provide for the self-administration of a medical product from a multi-dose cartridge and allow the user to set the delivery dose. This application may find application in devices for drug delivery of both disposable and reusable types. However, the features of the present invention may equally be applicable in other cases.

BACKGROUND OF THE INVENTION

Syringe pen-type drug delivery devices are used if regular injections are made by individuals without special medical training. This is becoming more common among patients with diabetes, where self-medication allows such patients to exercise effective control over their disease. It has been shown that diabetes causes certain problems. For example, people with diabetes can develop high blood pressure, kidney disease, nerve damage, heart disease, and in some cases even blindness. Damage caused by these problems can occur in patients whose blood sugar levels have been uncontrolled for years. Controlling blood sugar levels by effectively administering insulin is one way that can help prevent damage.

In addition, people with diabetes can fall into a “diabetic coma” if their blood sugar is too high. Also, they may develop too low blood sugar (i.e. hypoglycemia) if they do not get enough food, or their physical activity is too high and is not accompanied by a corresponding change in the amount of insulin or food. Both diabetic coma and hypoglycemia can be very serious and even fatal without prompt treatment. Careful monitoring of blood sugar levels, awareness of the early signs and symptoms of too high or too low blood sugar levels and early treatment of such conditions can prevent these problems from developing leading to serious conditions.

Pen-type drug delivery devices are designed and developed to help patients suffering from diabetes and other painful conditions, as well as to prevent the occurrence of such problems. The circumstances mentioned above underline a number of design decisions and criteria for drug delivery devices, especially those that can be used to treat diabetes. As just one example, one requirement is for the drug delivery device to have a robust design. A drug delivery device should also be easy to use both in terms of handling the drug delivery device and understanding the operation of the device. Diabetics, for example, often have to inject themselves with an insulin solution, and the amount of insulin to be administered may vary from patient to patient, and even from injection to injection. For at least this reason, certain diabetics may need drug delivery devices that allow the patient to administer sequential, measured doses of the same or possibly different pre-determined volumes of insulin solution accurately and with minimal dexterity requirements. This is another design feature because, in the case of individual diabetics, users may have low vision and / or may be physically weak with limited dexterity.

Typically, pen-type drug delivery devices comprise a cartridge having a sliding piston and containing a multi-dose liquid drug. The lead screw coming out of the syringe pen dose setting mechanism is arranged to move forward (i.e., in the far direction) to advance the piston in the cartridge so as to dispense the drug contained therein from the outlet at the opposite end of the cartridge, as typically through a needle that passes through a stop or membrane at this opposite end. In the case of disposable or pre-filled syringe pens, where the cartridge is sealed in the pen body, after using the entire drug pen contained in the cartridge, the entire syringe pen is discarded. In reusable syringe pens, after using the entire drug pen contained in the cartridge, the syringe pen is disassembled to replace the used cartridge with a new cartridge, and then the pen is reassembled for subsequent use.

A number of injection devices such as a pen are available for purchase, but, unfortunately, a number of these devices have one or more design flaws that can lead to improper use of the injection device or delivery of an inaccurate dosage of the drug. Inaccurate dose setting can be fatal. Other design flaws make it possible to improperly disassemble the disposable pen and insert a fake drug cartridge. This pen is then reassembled and sold as new. Such design flaws cannot be detected when the syringe pen first appears on the market and can only manifest itself after the injection device has been in commercial use by patients for an extended period of time. As such, there is a need to evaluate existing designs of syringe pens to determine structural flaws and then carry out their correction, which typically involves redesigning certain original mechanisms in the injection device.

One such injector handle in need of improved design is described in WO 2005/0188721. The following describes a number of such design flaws and presents corrective solutions to address these drawbacks.

SUMMARY OF THE INVENTION

In most, if not all, pen-type injection devices, dose accuracy is largely not observed if the distal end of the lead screw, through an appropriate support, is not permanently engaged with the proximal end or end of the cartridge piston before the user sets the dose. In other words, in some designs of the metering mechanism, there are one or more drawbacks that allow the lead screw to move or otherwise move the piston in the near direction after the dose has been administered and before the next dose is set. In these cases, the support is no longer in contact with the proximal end of the piston, thereby creating a gap or empty space between the distal surface of the support and the proximal surface of the piston. When the next dose is set and delivered, the lead screw must pass this unintended gap before contact with the piston and its movement. Since the piston does not move during the reduction of this gap and, therefore, the drug is not pushed out of the cartridge, the actual delivered dose will be less than the amount set directly proportional to the size of the gap. Accordingly, preventing any unexpected movement of the lead screw in the near direction between dose delivery and setting the next dose is of utmost importance. In other words, the dispensing mechanism should include structures that prevent the propeller from moving in the near direction relative to the cartridge piston.

A physical study of a pen-type commercial injection device, which is generally described in WO 2005/018721, shows that if the user presses the metering head in the far direction and at the same time rotates the metering head in either direction (clockwise or counterclockwise), the lead screw advances either in the near or in the far directions.

Another obvious problem with this commercial injection device is that it is a pen-type device with a fully manual drive. That is, this commercial syringe pen for drug delivery can be considered as a manual syringe pen, since the administration of the medicine contained in the syringe pen is carried out only with the help of the force exerted by the syringe pen user. Essentially, some kind of mechanism, such as a spring part, is not involved in drug administration. One drawback of such a purely manual syringe pen is that the user has to exert force to push the dose-setting element to a predetermined axial distance, and then press the dose-setting element to inject. This can be a difficult manual operation, especially for people with reduced motor skills or weak fingers, such as children, the elderly, people with disabilities, or people with diabetes. To solve this problem, in the present invention, the original design of the dispensing mechanism has been changed so as to ensure the participation of the spring device during the dose administration stage.

This disclosure relates to a method and system for performing drug delivery using a spring mechanism. A device with a spring mechanism for drug delivery may include a housing and a screw having a longitudinal axis, a distal end and a proximal end, which is fixed without rotation during dose setting and dose delivery and is able to move along the axis in the far direction relative to the housing. The lead screw may include a threaded rod and a support leg connected to the distal end, where the lead screw has a smooth keyway located parallel to the longitudinal axis. A cartridge with a movable piston at one end and an outlet at the other end may be provided. The piston is capable of engaging with a rotor of the rotor in order to advance in the direction of said outlet when the rotor moves in the far direction. The drive nut is in threaded engagement with the threaded rod of the drive screw and is configured to helically move along it. The digital drum is threadedly engaged with the housing in order to be able to perform helical movement relative to the housing. The middle case is fixed without the possibility of movement along the axis inside the case, the middle case contains dowels that can slide into the keyway on the lead screw to make it impossible to rotate the lead screw in the case. A pre-tensioned spring is provided that assists the user of the device during the dosing step.

The main idea is to provide a device with a spring mechanism for drug delivery, comprising a housing, a piston rod having a longitudinal axis, a distal end and a proximal end, and configured to move along the axis in the far direction relative to the housing. The drug delivery device further comprises a median housing fixed inside the housing and coupled to the piston rod so that the piston rod is able to move along the axis in the far direction relative to the median housing. The pre-tensioned spring is operatively connected to the piston rod in such a way that the spring is released and the energy stored in the spring helps to drive the piston rod in the far direction during the dose-introducing step.

The middle body and the body can be molded as a single unit or be separate components interconnected. The connection may be permanent or detachable. The median body is at least secured without being able to move along an axis within the body.

Since the invention is not limited to a lead screw, which can be used to convert rotational motion to linear motion, the term "piston rod" is used. The term "piston rod" preferably means a component adapted to extend throughout / within the housing of the delivery device, which may be designed to move along the axis throughout / within the delivery device, for example, to release or dispense the product for injection. "Piston rod" further means a component having a circular cross-section or other than circular. It can be made of any suitable material known to a person skilled in the art, and its construction may consist of one or more parts. One embodiment of a piston rod may be a threaded spindle.

Functionally related components can be linked directly to each other, for example, to be connected or to mesh, or indirectly, i.e. through other components. The components can be joined by matching molds, press fit or binder material. Alternatively, the components can only touch each other or abut against each other so that the force or motion can be transmitted. The coupled components may or may not be able to move, for example, along an axis and / or rotationally relative to each other.

In one embodiment, the pre-tensioned spring is operatively connected between the median housing and the piston rod, or between the housing and the piston rod. The pre-tensioned spring can be functionally connected between the median housing and the piston rod support. In one embodiment, the pre-tensioned spring is operatively associated with a separate component with a support surface attached to the proximal surface of the support. The pre-tensioned spring may comprise a wave spring, which may be in functional communication with the proximal surface of the support. The piston rod can be made as a spindle, which includes a threaded rod and a support connected to the distal end.

For example, in one arrangement, a change in the middle body and the support of the spindle of the handle type delivery device is made to accommodate the spring. Such a spring may be a compression spring or a wave spring or other similar biasing part. In this arrangement, in which the device is provided to the user, the spring is preferably provided in a pre-tensioned or pre-stressed state. This pre-tensioned spring determines the force of the spring, which can be applied during the dose administration step and, therefore, the reduction of the force exerted by the user to administer the dose. As described in detail herein, one end of the spring can be secured to the middle housing, and the other end of the spring can be secured to the support surface of a separate component attached to the support of the lead screw.

When the user presses the dosing head to administer the selected dose of the drug contained in the syringe pen, the pre-tensioned spring is released and the energy stored therein facilitates or facilitates the injection, driving the lead screw in the far direction. Essentially, in this arrangement, for the injection to be performed, the user needs to apply less force than when using the device without a spring.

A pen-type drug delivery device having the design improvement described above comprises a housing and a lead screw having a longitudinal axis, a distal end, a proximal end and a threaded rod. The lead screw is fixed without rotation during exposure and injection of the dose and moves only along the axis in the far direction relative to the housing during dose administration. The lead screw may include a support leg connected to the distal end. The lead screw may have a smooth keyway located parallel to the longitudinal axis. In one embodiment, the lead screw is never able to move in the near direction. The device also has a fluid container or cartridge defining a drug-filled container with a movable piston at one end and an outlet at the other end, where the piston is engaged with a support connected to the distal end of the lead screw. The piston advances toward the outlet or the far end of the cartridge when the lead screw moves in the far direction during dose administration. The piston may be able to engage with the lead screw support in order to advance in the direction of said outlet when the lead screw moves in the far direction.

The drive nut is threadedly engaged with the threads on the lead screw and can rotate and move in the near direction relative to the lead screw and housing during dose setting. In other words, the drive nut is threadedly engaged with the threaded rod of the drive screw and is configured to screw through it. The digital drum is threadedly engaged with the housing, which allows it to perform helical movement relative to the housing. The digital drum is unscrewed outward in a short direction relative to the housing during dose setting. The middle case is fixed without the possibility of movement along the axis inside the case, the middle case contains dowels that can slide into the keyway on the lead screw to make it impossible to rotate the lead screw in the case. A pre-tensioned spring is provided that assists the user of the device during the dosing step.

The swing arm can be connected to the drive nut and is able to move along the axis, but is fixed without rotation relative to the drive nut, and the swing arm is fixed without rotation with the digital drum when the swing arm and digital drum are in the first axial configuration. The digital drum is able to rotate relative to the swing arm when the swing arm and the digital drum are in a second axial configuration. In one embodiment, the pivoting link is slidably engaged and pivotable with the drive nut and is movable along the axis and secured without rotation relative to the drive nut. The swing arm is rotatably fixed to the digital drum by means of a clutch, when the swing arm and digital drum are in the first axial configuration, and in the second axial configuration, the coupling, and therefore the digital drum, are detached from the swing arm, and the swing arm is rotated relative to the digital drum. The inner drum is threadedly engaged with the digital drum, where the inner drum is made to move along the axis, but is fixed without rotation relative to the housing. The inner drum is able to move along the axis and is fixed without rotation relative to the middle body by, for example, at least one spike of the middle body, which slides into at least one groove formed in the internal drum.

In one embodiment, the median body further comprises at least one metal ratchet lever designed to make it impossible to move the spindle in the near direction.

In one embodiment, the threaded engagement of the digital drum with the housing has a first step, the threaded engagement of the inner drum with a digital drum has a second step, and the thread of the threaded shaft of the lead screw has a third step, the first step, second step and third step being different from each other.

During dose setting, the swing arm and the digital drum are in a first axial configuration in which the screw movement of the swing arm and the digital drum relative to the housing unscrews the swing arm and the digital drum a first axial distance from the starting position. The screw movement can occur due to the screw movement of the dosing head, which is connected to the rotary link and the digital drum relative to the housing. The screw movement of the dosing head unscrews the rotary link and the digital drum by a first axial distance from the initial position, forcing the digital drum to extend in the near direction from the housing or the main part of the device. The screw movement of the swing arm rotates the drive nut along the threaded shaft of the lead screw by a second axial distance different from the first axial distance.

During the dose delivery, the rotary link and the digital drum part are in the second axial configuration, so that the helical movement of the digital drum relative to the housing back or inward to the initial position moves the inner drum without rotation in the far direction in order to move the drive nut along the axis, and therefore a lead screw and a movable piston of a fluid container to dispense medicament or fluid from the outlet of the cartridge. The drive nut is fastened without the possibility of movement along the axis with the inner drum.

The injection handle disclosed herein can be provided with a mechanical advantage that facilitates the user pressing the dosage head during dispensing of the drug; this mechanical advantage can be very significant and successfully selected by the manufacturer during the design of the device. This mechanical advantage allows the digital drum to travel a greater axial distance than the lead screw advances, thereby allowing the delivery of small doses.

These, as well as other advantages of various aspects of our improved drug delivery device, and the method for achieving them, will be apparent to those of ordinary skill in the art by reading the following detailed description with the appropriate reference to the accompanying graphic materials.

A brief description of the graphic materials

Illustrative embodiments are described herein with reference to graphic materials in which:

in FIG. 1 is a depiction of one embodiment of the present invention, representing an assembled pen-type drug dispensing device in which the cap is removed so that a cartridge container attached to a dose setting mechanism is visible;

in FIG. 2 is a close-up view of the cartridge container and the syringe pen needle that is attached to the cartridge container for drug injection;

in FIG. 3 is an exploded view of the embodiment of FIG. 1, representing each of the individual parts located relative to each other as they are placed in a fully assembled device;

in FIG. 4 is a perspective view of one embodiment of a syringe pen device with a spring mechanism in a set-up position with a pre-tensioned spring;

in FIG. 5 is a perspective view of the embodiment of FIG. 4, in the dispensing position;

in FIG. 6 is a close-up view of the distal end of the spring of the spring-loaded syringe pen device of FIG. four;

in FIG. 7 is a perspective view of an alternative embodiment of a syringe pen device with a spring mechanism in a prepared position for a set with a pre-tensioned wave spring;

in FIG. 8 is a perspective view of the embodiment of FIG. 7, in the dispensing position; and

in FIG. 9 is a close-up view of the distal end of the spring of the syringe pen device with the spring mechanism of FIG. four.

Corresponding link symbols indicate corresponding parts throughout the series of images. Although the graphic materials represent embodiments of the present invention, the graphic materials are not necessarily to scale, and on certain graphic materials certain details may be exaggerated or omitted to better illustrate and explain the present invention.

Detailed description

Turning to FIG. 1-3, a drug delivery device 1 is provided in the form of a pen-injector, the pen having an oblong, substantially similar to a writing device form, although other forms are within the scope of the present invention. In other words, the drug delivery device 1 may be a pen-type device. The drug delivery device 1 comprises a housing having a cartridge holder 2 and a main (external) body or housing 4.

The drug delivery device 1 and the housing have a distal end and a proximal end. The term “distal end” means that end of the drug delivery device 1 or its component that is located or should be located closest to the delivery end of the drug delivery device 1. The term "proximal end" refers to that end of the device 1 or its component that is located or should be located farthest from the output end of the device 1. The far end and the proximal end are spaced from each other in the axis direction. The axis may be a longitudinal axis or an axis of rotation of the device 1.

The near end of the cartridge holder 2 and the far end of the main body 4 are fastened together with respective holding devices, depending on whether the injector handle is designed as a reusable device or as a disposable device. In the latter case, the holding device will be permanent using the connecting means described below. If the device is reusable, the retaining means will be a screw connection, Luer tip, latch, bayonet lock or the like, or a combination of connecting elements that allows the user to easily disassemble the device to replace an empty cartridge with a new cartridge. In this arrangement shown, the cartridge holder 2 is fixed at the proximal end of the main body 4.

A cartridge 8, from which a series of doses of a medical product can be dispensed, is provided in the cartridge holder 2. Preferably, the cartridge 8 contains a type of drug that requires frequent administration, such as once a day or more often. One such drug is insulin. The piston 10 is first held at the proximal end of the cartridge 8 and, as each injection is completed, gradually moves further to the empty cartridge position shown in FIG. 2. The removable cap 14 is held detachably connected to the main body 4, closing the cartridge holder 2.

The dose setting mechanism of the drug delivery device of FIG. 1-3, can be used either for a disposable or reusable drug delivery device. When the drug delivery device 1 is a disposable drug delivery device, the cartridge 8 cannot be removed from the drug delivery device 1 without destroying the device 1. In the disposable device, the proximal end of the cartridge holder 2 can be firmly mounted or secured with adhesives, ultrasonic welding, or other suitable method with the body of the dose-setting mechanism during assembly of the injector handle by the manufacturer. Alternatively, when the drug delivery device 1 is a reusable drug delivery device, the cartridge 8 is removable and can be removed from the drug delivery device 1 without destroying the device 1. In the drug delivery device 1 shown on FIG. 1-3, the device is presented as a disposable device 1 for drug delivery. However, those skilled in the art will understand that this dose setting mechanism can also be used in a reusable drug delivery device, where in the case of a reusable syringe pen where the cartridge holder 2 can be reusable, the proximal end can be removably mounted or fixed, for example, using a threaded, bayonet or snap-on connection, in a reusable drug delivery device equipped with a resettable lead screw.

The previously mentioned removable or interchangeable cap 14 is used to cover the cartridge holder 2 protruding from the main body 4. Preferably, the external dimensions of the interchangeable cap 14 are similar or identical to the external dimensions of the main body 4 to give the impression of an integral part when the interchangeable cap 14 is in the position covering holder 2 cartridges. In use, the removable cap 14 is removed, and the handle needle assembly 16 containing the double-sided needle mounted on the sleeve can be screwed on or mounted on the far end of the cartridge holder 2, or, alternatively, can be snapped on this far end.

Cartridge 8 has a traditional design and is a medicament-filled reservoir, closed from its proximal end by a piston 10, which in the axial direction is movably and tightly in contact with the inner wall of the cartridge, holding the liquid medicine inside the reservoir. The far outlet end of the cartridge reservoir is covered by a membrane 11 held by a cap 13, which is mounted on the neck 15 with a decreasing diameter of the cartridge 8. When the needle assembly 16 of the syringe pen is mounted on the far end of the cartridge holder 2, the proximal point of the injection needle passes through a central hole at the far end cartridge holder 2, the hole in the cap 13 and penetrates through the membrane 11, providing an outlet for the liquid flow through which the drug can be dispensed from the cartridge reservoir through the far end of the needle performed syringe handle 1 operation. The cartridge 8 for liquid medicine, presented and described above, is illustrative and is not intended to be limiting, since other designs can be used in the framework of the present invention.

In the main body 4 of the syringe pen 1, an axial screw 22, a drive nut 23, an inner drum 29, a rotary link 25, a digital drum 24, a clutch 26 and a compression spring 27 are placed axially moving forward. The metering head 28 is connected to the rotary link 25 and used to set the dose and then to introduce the set dose. The body or main body 4 is molded from lightweight material such as injection molded plastic. For reliability, the housing 4 can be molded as a single tubular element. The hole 51 in the housing 4 near its proximal end can be equipped with a magnifying lens with a snap mechanism for attaching to the housing 4, which during use makes it easier to read numbers from the digital drum 24 indicating the digital dosage marking (not shown).

Near the far end of the inner part of the casing 4, a median casing 20 is installed, which is formed with a central hole having an inward-facing counter-rotating mechanism formed of a pair of diametrically opposite elements or keys 31 having rectangular inward-facing ends, each of which can slide into the longitudinal keys slots 32 on the lead screw 22. In alternative embodiments, devices other than the keys 31 and keyways, for example, a lead screw with chamfers that enter a suitably formed hole in the ring. The dowels 31 prevent the spindle 22 in the housing 4 from turning during use of the syringe pen, but allow longitudinal movement of the spindle 22, such as movement in the far end direction, toward the cartridge 8. To prevent axial and rotational relative motion of the middle body 20 with respect to to the tubular body 4, a snap-in connection or ultrasonic welding of the middle body 20 with the body 4 can be used.

The lead screw 22 is in the form of a screw, which is made with the possibility of movement along the axis and without the possibility of rotation during dosing and injection. The term "fixed without rotation" in this context should mean that during dosing and injection, the rotation of the screw 22 is not allowed. The lead screw 22 contains a rod with a screw thread 33 along its length, this thread 33 is interrupted by longitudinally extending keyways or grooves 32. A threaded stop 34, presented at the proximal end of the thread 33, is provided and used to prevent the user from setting the dose of medication for delivery with a syringe pen 1 more than is left in the cartridge 2. The scope of the invention also covers other screw-stopping forms, for example, thread 33 at the proximal end of the screw can end near the proximal end, where there is no engagement, and a one-piece screw threaded abutment better prevents folding of the nut 23 with the screw during the issuing dose. At the distal end of the lead screw 22 is an enlarged support leg or disk-shaped support 21 for distributing the load on the cartridge piston 10, with which the bearing 21 is in contact and, as a result, comes into direct engagement as the piston advances. A separate support leg 21 can be attached, for example, by means of a latch 20, allowing relative rotation, to the lead screw 22. The lead screw 22 is presented as a single molded plastic part, but alternative construction materials and several parts are possible.

The drive nut 23 contains a cylindrical tube-like body with flexible fingers 36 and dog teeth 35. The far region of the drive nut 23 is formed with an internal thread 37, which, by means of a friction clutch thread, engages with a thread 33 on the lead screw 22. Threads 33 and 37 are depicted in the form two-way threads, but can be formed in a different way, which will still provide suitable friction clutch functions, for example, in the form of a single-thread or other multi-thread. The drive nut 23 is located in the inner drum 29 and is fixed without the possibility of movement along the axis, but with the possibility of rotation, on the inner drum 29. When the drive nut 23 is rotated relative to the inner drum 29 during dose setting, the teeth of the dog 35 engage as in a ratchet , with flexible arrows 38 that protrude in a radial direction from the inside of the inner drum 29. As the drive nut 23 rotates, the flexible arrows 38 jump over the teeth 35, creating an audible click sound. The teeth 35 are made so that each click is equal to the volume of one set dose. Only one flexible snapping arrow 38 may be provided, but using four evenly spaced arrows of the same angle 38 facilitates centering of the drive nut 23 within the inner drum 29. The hollow interior of the body of the drive nut 23 located on the proximal end of the thread 37 allows free passage of the proximal the end of the drive screw 22. The outer surface of the drive nut 23 is designed for mutual engagement with the swing arm 25, so that the swing arm 25 can move along about and, but fixed without rotation relative to the drive nut 23. Thus, during use, the rotary link 25 is movable along the axis, but fixed without rotation relative to the threaded drive nut 23. This connection is possible due to the interaction of the fingers passing in the near direction 36 on the drive nut 23 and the long-distance fingers 43 of the swing arm 25. These two sets of fingers 36, 43 move axially relative to each other, but engage with each other when turning during dose setting, when the swing arm 25 is rotated by turning the metering head 28, which is attached to the swing arm 25. The drive nut 23 is presented as a single plastic injection molded member, although other designs are covered by the scope of the present invention.

In the present embodiment, the swing arm 25 is formed by one injection molded plastic member that is inserted into the body 4. The flange 40, which surrounds the central body region of the swing arm, contains slots or teeth 39 that extend from the far surface of the flange 40, and teeth 41, which extend from the proximal surface of the flange 40. The diminishing portion of the proximal end of the swing arm 25 forms a rod 42 extending along the axis and towards the proximal end. The distal end of the swing arm body a pair of pins 43 that correspond to the fingers 36 of the drive nut 23, allowing movement along the axis, but not rotational movement of the drive nut 23 about the pivot wings 25, thus blocking the possibility of co-rotation of these parts within a circular space. The fingers 36 and 43 extend substantially along the axis to ensure that they are not disengaged during setting the maximum dose for injection from the syringe pen.

The dosing head 28 with the near end is provided in injection molded plastic and has a long-distance and centrally located support ring and a mounting pin 55. The shaft 42 of the rotary link 25 receives the mounting pin of the dosing head and can be ultrasonically welded inside the support ring into assembly time in such a way as to fasten in the axial and rotational directions the dosing head 28 with a rotary link 25. The term ʺ fix without possibility rotation in this context should mean that any relative rotational movement between the dosing head 28 and the swinging arm 25 is prevented. The skirt 50 of the dosing head extends far from the radial peripheral part of the far end of the dosing head to serve as a gripping part for the user to set the dose .

A digital drum 24 is coaxially mounted around the swing arm 25. The digital drum 24 has a cylindrical outer surface 30 with a thread 52 formed in the form of a spiral groove, which engages with a corresponding thread 62 formed on the inner surface of the main body 4 to engage with the thread 24 digital drum with a housing 4 syringe pens. Threads 52 and 62 are presented as single-threading, but can be formed differently. The thread 62 abuts the end 63 of the thread 52 on the digital drum 24 when setting the maximum dose on the syringe pen, provided that the cartridge 8 is full enough for such a maximum dose. The abutment surface 64 at the far end of the outer surface of the digital drum 24 is located a short distance from the protruding abutment in the zero-dose position, and the abutment should abut against another abutment surface if the user tries to manually screw the screw element below the zero-dose position. The hollow interior 65 of the digital drum 24 is defined by a cylindrical inner surface provided with a screw thread 67.

The outer diameter of the digital drum 24 is selected so that it can be inserted inside the dosing head 28. The near end region of the digital drum 24 contains a number of recesses 70 and corresponding windows 71 that are alternately spaced around the circumference. Around its outer surface 30, the digital drum 24 has a suitable therapeutic dose scale that can be seen through the opening 51 of the body 4. The sleeve 26 is inserted into the open proximal end of the digital drum 24. The tabs 72 on the sleeve 26 are inserted into the recesses 70 and the assembly fingers 73 snap into windows 71 for blocking the joint movement along the axis and rotation of the digital drum 24 and the clutch 26 during the production assembly. The ring of axially extending teeth 54 on the coupling 26 formed on the inner surface of the flange interacts with the teeth 41 of the swing arm that are turned in the near direction on the swing arm 25.

Between the sleeve 26 and the inside of the metering head 28, there is a push or bias spring 27 which forces the sleeve 26 to engage with the teeth 41 on the swing arm 25. During injection, when the user manually applies a forward force to the near end of the metering head 28, the spring 27 is elastically compressed, thereby disengaging the clutch 26 and the digital drum 24 from the swing arm 25. The flange teeth 41 on the swing arm 25 and clutch teeth 54 engage when the spring 27 biases the sleeve 26 and fastens the digital bar Aban 24 with the metering head 28 and the swing arm 25. The metering head 28 and the swing arm 25 are not engaged with the clutch 26 and the digital drum 24, when the spring 27 was sufficiently compressed during the injection. Although a spirally twisted metal wire spring 27 is shown, other forms of well-known biasing elements may be used instead.

The inner drum 29 is injection molded from plastic and includes a tubular body that enters the cavity 65 of the digital drum 24. The inner drum 29 has a screw thread 75 on its outer surface that engages with an inner thread 67 on the inner surface of the digital drum 24. Threads 67 and 75 are presented as single-threading, but can be formed differently. The closest part of the end of the inner drum 24, whose end has a partially helical shape corresponding to the thread, is serrated with the formation of a partial ring of teeth protruding along the axis 76, which, when engaged with the teeth in the far direction 39 of the swing arm, are used to block the swing arm 25 without rotation and the inner drum 29. The inner drum 29 is attached to the body 4 of the syringe pen using the intermediate median body 20, which is fixed without the possibility of movement along the axis and rotation with the body 4 The far end of the inner drum 29 has a pair of flange-bordered sockets 77 on the peripheral part of the inner drum 29, which receive along the axis with the possibility of sliding spikes 78, protruding in the radial direction inward from the middle body 20.

The holes formed in the inner drum 29 define four elastic fingers 38 having teeth protruding radially inward, which are oriented along the axis and are shaped to extend into a recess in the distal end of the drive nut 23 that has teeth radially protruding or the beads 35, so that the inwardly protruding teeth snap in any direction of rotation on the teeth 35 during dose setting. The fingers 38 with teeth interact with a recess on the drive nut 23 to prevent the drive nut 23 from coming out of the inner drum 29 after being inserted into it during production.

To simplify the retraction during dose delivery, the threaded connections of the digital drum 24 and the main part 4 and the digital drum 24 and the inner drum 29 are non-limiting and are represented by protrusion of threads with a 60 ° cone angle that slide along appropriately designed recessed channels. With these threads, preferably, the gain in force is 3.4 or more, and the thread pitch of the drive member or drive nut 23 is 0.108 inches.

Now, the operation of the above embodiment will be explained. The syringe pen 1 with the needle 16 attached must first be prepared by removing any air that has entered the cartridge 8 and making sure that the carrier 21 is in contact with the proximal end of the cartridge stopper or piston 10. In particular, as a rule, when clamping the body 4 of the syringe pen in one hand, the user grasps the skirt 50 of the dosing head with his hand and then starts to rotate the dosing head 28 relative to the body 4. In the zero-dose position and until the dosing head 28 is also pressed, which is wrong, the dosing head 28 can only be rotated in the direction of increasing the dose due to the fact that the digital drum 24 cannot be further moved in the far direction. The user stops rotation after a short movement of the digital drum 24, which is associated with a small delivery volume, for example, with one or two units, as indicated by the marks visible through the hole 51. Then, after removing the cap 14 and any other available cap on the needle, and directing the tip of the needle up, the user applies a forward force to the metering head 28 to move it in the far direction until the digital drum 24 returns to the zero-dose position, in which the thread 52 of the digital bar the abana reaches the far end of the thread 62 of the housing, during this forward action, the piston 10 moves forward in the cartridge 8. If the user sees that the movement of the piston has led to the liquid reaching the far tip of the needle, the preparation process is completed. If fluid is not visible at the tip of the needle, the preparation steps are repeated as necessary. After preparation, the syringe pen 1 is ready for use for the actual injection.

First, the user prepares the syringe pen by setting the desired dose, as seen in hole 51, by turning the dosage head 28. If the user draws a too large dose, then without losing medication, the user can turn the kit back by turning the dosage head 28 in the opposite direction, right to zero if necessary. To set the dose, the dosing head 28 is rotated clockwise. Since the metering head 28 and the rotary link 25 are rotationally fixed, the rotary link 25 rotates, causing the long-facing fingers 43 to engage with the short-facing fingers 36 of the drive nut 23 to thereby rotate the drive nut 23 in the same direction. The rotation of the drive nut 23 rotates the nut 23 relative to the stationary spindle 22, whereby the nut 23 moves or rises along the spindle 22 in the near direction. The drive nut 23 rotates relative to the inner drum 29, which is held fixed rotatably relative to the main part 4 by means of a spline connection with the middle body 20. Since the drive nut 23 and the inner drum 29 are axially fixed, the nut movement 23 along the axis in the near direction provides sliding the inner drum 29 in the near direction relative to the middle body 20. Since the clutch 26 is fixed without rotation with a rotary link 25, the clutch 26 It causes the rotation and unscrewing of the digital drum 24 in the near direction from the body 4. Since the thread pitch on the digital drum 24 is larger than the thread pitch on the inner drum 29, the digital drum 24 and the swing arm 25 will translationally move a greater axial distance than the inner drum 29 and the drive nut 23.

To introduce a dose, after the syringe pen 1 is operated in such a way that the distal tip of the injection needle penetrates properly, for example, a force is applied to the end face 53 of the head through the skin of the user in the far direction to advance the swing arm 25 along the b axis far direction to the body 4, for example, with the thumb or forefinger of the hand that compresses the housing 4. First, during the injection, the swing arm 25 is displaced along the axis, this biasing movement compresses the biasing spring 27 to close the gap between the head surface and the proximal end of the digital drum 24. The bias spring 27 is designed to be compressed before the digital drum 24 is moved relative to the housing 4. When the swing arm 25 moves relative to the digital drum 24 to the axial configuration of the drive nut 23, the teeth 54 of the clutch and the teeth 42 of the swing arm are disengaged from providing reverse rotation of the digital drum 24 relative to the rotary link 25. During the axial movement of the rotary link 25, the drive nut 23 does not perform axial or rotational movement tions. When the digital drum 24 and the clutch 26 are rotatably disconnected from the rotary link 25, as the rotary link 25 continues to move forward without rotation by the user by directing the metering head 28 forward, the digital drum 24 is screwed into the body 4 as it rotates relative to the metering head 28, and the dose marks on the digital drum 24, which indicate the amount still remaining for injection, are visible through the hole 51.

As the screw is screwed in, the digital drum 24 essentially screws the inner drum 29 through the internal thread inside the thread of the digital drum as the inner drum 29 moves farther away than the digital drum 24. The inner drum 29 advances due to abutment or direct engagement with the far end of the drive nut 23, advances the drive nut 23 without rotation, which, thanks to its threaded connection with the lead screw 22, advances the lead screw 22 along the axis without rotation Niya, this advancement of the lead screw displaces the piston 10 of the cartridge to eject the drug from the cartridge. Injection is completed when the thread 52 of the digital drum reaches the far end of the body 4, at which time the syringe pen 1 again enters the ready state or the zero-dose position.

The syringe pen 1 can continue to be used to deliver any desired dose until the medication remaining in cartridge 8 is insufficient for proper dosage. This insufficient amount is indicated to the user by the impossibility of completely setting the desired dose due to the stop of the thread 37 of the drive nut in the threaded stop 34 on the lead screw 22, at this moment the drive nut 23 and the rotary link 25 can no longer rotate in the near direction. When there is not enough drug left, the syringe pen 1 must be thrown out and replaced with a similar but completely new pen.

As discussed above, one obvious problem with this commercial injection device is that it is completely manual. That is, this commercial syringe pen for drug delivery can be considered as a manual syringe pen, since the administration of the medicine contained in the syringe pen is carried out only with the help of the force exerted by the syringe pen user. Essentially, no type of spring mechanism is involved in the administration of the drug. One drawback of such a purely manual syringe pen is that the user has to exert force to push the dose-setting element to a predetermined axial distance, and then press the dose-setting element to inject. This can be a difficult manual operation, especially for people with reduced motor skills or weak fingers, such as children, the elderly, people with disabilities, or people with diabetes. To solve this problem, in the present invention, the original design of the dispensing mechanism has been changed so as to ensure the participation of the spring device during the dose administration stage.

For example, Figure 4 is a perspective view of one embodiment of a syringe pen device 80 with a spring mechanism in a position prepared for collection. As shown, this spring-loaded syringe pen device 80 includes a tensioned or pre-tensioned spring 82 that is sandwiched between the distal end of the median body 20 and a separate support surface component 81 that is attached to the support 21 on the spindle 22.

For example, in FIG. 6, a close-up view of the distal end 84 of the spring 82 is shown, and how it interacts with the lead screw support 21. As shown, the support 21 further includes a separate support surface component 81 that defines a recess 83. Within this recess 83 is a distal the end 84 of the spring 82. In this configuration, the support surface component 81 is designed to dampen the rotational force of the spring 82. The support surface component 81 is rigidly attached to the proximal surface 85 of the support 21 of the lead screw 22. Returning to FIG. 4, the proximal end 86 of the tension spring 82 is rigidly attached to the middle body 20.

As described above, to set the dose using this first embodiment of the spring mechanism, the dosing head 28 is rotated clockwise. Since the metering head 28 and the swing arm 25 are rotatably fastened, the swing arm 25 rotates, causing the fingers 43 facing in the far direction to engage with the fingers 36 of the drive nut 23 in the near direction, so that the drive nut 23 can be turned in the same direction . The rotation of the drive nut 23 rotates the nut 23 relative to the stationary spindle 22, whereby the nut 23 moves or rises along the spindle 22 in the near direction. The drive nut 23 rotates relative to the inner drum 29, which is held fixed rotatably relative to the main part 4 by means of a spline connection with the middle body 20. Since the drive nut 23 and the inner drum 29 are axially fixed, the nut movement 23 along the axis in the near direction provides sliding the inner drum 29 in the near direction relative to the middle body 20. One advantage of the spring-loaded delivery device shown in FIG. 4 is that dose setting is not affected by the presence of a pre-tensioned spring 82. In fact, the user does not need to exert additional force when setting the dose.

In order to administer a dose and in a similar manner to the device discussed previously with reference to Figures 1-3, a force directed forward in the far direction is applied to the end face 53 of the head to advance the swing arm 25 along the axis in the far direction to the body 4, for example, with the thumb or forefinger which compresses the housing 4. First, during the injection, the swing arm 25 is displaced along the axis, this biasing movement compresses the biasing spring 27 to close the gap between the head surface and the proximal end of the digital drum 24. Biasing the springs 27 is designed to be compressed before the digital drum 24 is moved relative to the housing 4. When the swing arm 25 is shifted relative to the digital drum 24 to the axial configuration of the drive nut 23, the teeth 54 of the clutch and the teeth 42 of the swing arm are disengaged to allow reverse rotation of the digital drum 24 relative to the swing arm 25. the axial movement of the rotary link 25 the drive nut 23 does not perform axial or rotational movement. When the digital drum 24 and the clutch 26 are rotatably disconnected from the rotary link 25, as the rotary link 25 continues to move forward without rotation by the user by directing the metering head 28 forward, the digital drum 24 is screwed into the body 4 as it rotates relative to the metering head 28, and the inner drum 29 moves in the far direction under the action of the force of the tense spring 82. Advance of the inner drum 29, due to emphasis or direct engagement from the far m the end of the drive nut 23, advances the drive nut 23 without rotation, which, thanks to its threaded connection with the lead screw 22, advances the lead screw 23 along the axis with a tension spring 82. Advancing the lead screw 22 by means of the spring biases the cartridge piston 10 to expel the drug from the cartridge reservoir . Injection is completed when the thread 52 of the digital drum reaches the far end of the main part 4, at which time the knob 1 again enters the ready state or zero position. In FIG. 5 is a perspective view of the embodiment of FIG. 4, in the dispensing position.

Figure 7 is a perspective view of an alternative embodiment of the device of the syringe pen 90 with a spring mechanism in a position prepared for collection. As shown, the device of the syringe pen 90 with a spring mechanism includes a tensioned or pre-tensioned wave spring 92. The wave spring may be a flat compression wire, for example, a corrugated metal washer. One embodiment may be a repeatedly crossed band spring. Such a spring is pre-stacked in series. One embodiment of a wave spring is a nest wave spring. Nest springs are pre-laid in parallel from one continuous strand of flat wire.

Such a wave spring 92 is placed between the middle body 20 and the proximal surface of the support 21 of the screw screw 22. In particular, the distal end 94 of the compressed or tensioned wave spring 92 is located along the proximal surface of the support 21 of the lead screw 22, and the proximal end 96 of the wave spring 92 is rigidly attached to the middle body 20. The user sets the dose on the device of the syringe pen 90 with the spring mechanism in a similar manner to how the user sets the dose on the device of the syringe pen 80 with the spring mechanism shown in FIG. 4-6. Similarly, one advantage of this spring-loaded syringe pen device 90 is that dose control is not affected by the presence of a wave spring 92, which means that no additional force is required in the dose setting process.

When the dose is set, when the user presses the metering head 28 to administer the selected dose of the drug contained in the syringe pen 90, the wave spring 92 is released, and the energy stored in the wave spring 92 helps to move or drive the screw screw 22 in the long direction during the stage injections. Essentially, in this arrangement, for the injection to be performed, the user needs to apply less force than when using the device without the spring. In FIG. 8 is a perspective view of the embodiment of FIG. 7, in the dispensing position, where the wave spring 92 is in a stretched state.

In FIG. 9 is a close-up view of the distal end 94 of the wave spring 92. As shown, the distal end 94 of the wave spring 92 is located directly on the proximal surface 95 of the support 21. In contrast to the configuration with the compressed spring 80 and the support 21 shown in FIG. 6, in the device of the syringe pen 90 with the wave spring mechanism, a separate component of the supporting surface attached to the support 21 is not required, since in the case of the wave spring 92 it is not necessary to extinguish any kind of rotational force.

The terms "drug" or "drug product", as used herein, means a pharmaceutical preparation containing at least one pharmaceutically active compound,

however, in one embodiment, the pharmaceutically active compound has a molecular weight of up to 1,500 Da and / or is a peptide, protein, polysaccharide, vaccine, DNA, RNA, enzyme, antibody or fragment thereof, a hormone or oligonucleotide or a mixture of the above pharmaceutically active compound,

in a further embodiment, the pharmaceutically active compound is useful for treating and / or preventing diabetes mellitus or complications associated with diabetes mellitus, such as diabetic retinopathy, thromboembolism disorders such as deep vein thromboembolism or pulmonary thromboembolism, acute coronary syndrome (ACS) , angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis,

in a further embodiment, the pharmaceutically active compound comprises at least one peptide for treating and / or preventing diabetes mellitus or complications associated with diabetes mellitus, such as diabetic retinopathy,

in a further embodiment, the pharmaceutically active compound comprises at least one human insulin or an analog or derivative of human insulin, a glucagon-like peptide (GLP-1) or its analog or derivative, or exendin-3 or exendin-4, or an analog or derivative of exendin- 3 or exendin-4.

Analogs of insulin are, for example, Gly (A21), Arg (B31), Arg (B32) human insulin; Lys (B3); Glu (B29) human insulin; Lys (B28), Pro (B29) human insulin; Asp (B28) human insulin; human insulin, where the proline at position B28 is replaced with Asp, Lys, Leu, Val or Ala and where at position B29 Lys can be replaced with Pro; Ala (B26) human insulin; Des (B28-B30) human insulin; Des (B27) human insulin and Des (B30) human insulin.

Derivatives of insulin are, for example, B29-N-myristoyl-des (B30) human insulin; B29-N-palmitoyl-des (B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N- (N-palmitoyl-Υ-glutamyl) -des (B30) human insulin; B29-N- (N-lithocholyl-Υ-glutamyl) -des (B30) human insulin; B29-N- (ω-carboxyheptadecanoyl) -des (B30) human insulin; and B29-N- (ω-carboxyheptadecanoyl) human insulin.

Exendin-4, for example, refers to exendin-4 (1-39), a peptide with the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu -Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 .

Exendin-4 derivatives, for example, are selected from the following list of compounds:

H- (Lys) 4-des Pro36, des Pro37 exendin-4 (1-39) -NH2,

H- (Lys) 5-des Pro36, des Pro37 exendin-4 (1-39) -NH2,

des Pro36 exendin-4 (1-39),

des Pro36 [Asp28] exendin-4 (1-39),

des Pro36 [IsoAsp28] exendin-4 (1-39),

des Pro36 [Met (O) 14, Asp28] exendin-4 (1-39),

des Pro36 [Met (O) 14, IsoAsp28] exendin-4 (1-39),

des Pro36 [Trp (O2) 25, Asp28] exendin-4 (1-39),

des Pro36 [Trp (O2) 25, IsoAsp28] exendin-4 (1-39),

des Pro36 [Met (O) 14 Trp (O2) 25, Asp28] exendin-4 (1-39),

des Pro36 [Met (O) 14 Trp (O2) 25, IsoAsp28] exendin-4 (1-39); or

des Pro36 [Asp28] exendin-4 (1-39),

des Pro36 [IsoAsp28] exendin-4 (1-39),

des Pro36 [Met (O) 14, Asp28] exendin-4 (1-39),

des Pro36 [Met (O) 14, IsoAsp28] exendin-4 (1-39),

des Pro36 [Trp (O2) 25, Asp28] exendin-4 (1-39),

des Pro36 [Trp (O2) 25, IsoAsp28] exendin-4 (1-39),

des Pro36 [Met (O) 14 Trp (O2) 25, Asp28] exendin-4 (1-39),

des Pro36 [Met (O) 14 Trp (O2) 25, IsoAsp28] exendin-4 (1-39),

wherein the —Lys6-NH2 group may be C-linked to the exendin-4 derivative;

or derivative of exendin-4 sequence

des Pro36 exendin-4 (1-39) -Lys6-NH2 (AVE0010),

H- (Lys) 6-des Pro36 [Asp28] exendin-4 (1-39) -Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38 exendin-4 (1-39) -NH2,

H- (Lys) 6-des Pro36, Pro38 [Asp28] exendin-4 (1-39) -NH2,

H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Asp28] exendin-4 (1-39) -NH2,

des Pro36, Pro37, Pro38 [Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H- (Lys) 6-des Pro36, Pro37, Pro38 [Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H- (Lys) 6-des Pro36 [Trp (O2) 25, Asp28] exendin-4 (1-39) -Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp (O2) 25] exendin-4 (1-39) -NH2,

H- (Lys) 6-des Pro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) -NH2,

H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) -NH2,

des Pro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H- (Lys) 6-des Pro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Trp (O2) 25, Asp28] exendin-4 (1-39) - (Lys) 6-NH2, H- (Lys) 6-des Pro36 [ Met (O) 14, Asp28] exendin-4 (1-39) -Lys6-NH2,

des [Met (O) 14 Asp28] Pro36, Pro37, Pro38 exendin-4 (1-39) -NH2,

H- (Lys) 6-des Pro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2,

H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2,

des Pro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H- (Lys) 6-des Pro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H-Lys6-des Pro36 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (1-39) -Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25] exendin-4 (1-39) -NH2,

H- (Lys) 6-des Pro36, Pro37, Pro38 [Met (O) 14, Asp28] exendin-4 (1-39) -NH2,

H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (1-39) -NH2,

des Pro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (1-39) - (Lys) 6-NH2,

H- (Lys) 6-des Pro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (S1-39) - (Lys) 6-NH2,

H-Asn- (Glu) 5-des Pro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] exendin-4 (1-39) - (Lys) 6-NH2;

or a pharmaceutically acceptable salt or solvate of any of the above exendin-4 derivatives.

Hormones are, for example, pituitary hormones, or hypothalamic hormones, or regulating active peptides and their antagonists, as indicated in Rote Liste, ed. 2008, chapter 50, such as gonadotropin (follitropin, lutropin, chorionic gonadotropin, menotropin), somatropin (somatotropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, goserelin.

The polysaccharide is, for example, glucosaminoglycan, hyaluronic acid, heparin, low molecular weight heparin or ultra low molecular weight heparin or a derivative thereof, or sulfated, for example polysulfated, form of the above polysaccharides, and / or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a polysulfated low molecular weight heparin is sodium enoxaparin.

Antibodies are globular plasma proteins (~ 150 kDa), which are also known as immunoglobulins, which have a common basic structure. Since they have sugar chains added to amino acid residues, they are glycoproteins. The main functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units, like IgA, tetrameric with four Ig units, like bony fish IgM, or pentamer with five Ig units, like mammalian IgM.

The Ig monomer is a "Y" -shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds between cysteine residues. Each heavy chain has a length of approximately 440 amino acids; each light chain has a length of about 220 amino acids. Each heavy and light chain contains intrachain disulfide bonds that stabilize their folding. Each chain consists of structural domains called Ig domains. These domains contain approximately 70-110 amino acids and are classified into various categories (e.g., variable or V, and constant or C) according to their size and function. They have a characteristic feature of the laying of the immunoglobulin chain, in which two β-sheets create a “sandwich” form, held together due to the interaction between stable cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain, designated α, δ, ε, γ, and μ. The type of heavy chain present determines the antibody isotype; these chains can be found in antibodies IgA, IgD, IgE, IgG and IgM, respectively.

Individual heavy chains differ in size and composition; α and γ contain approximately 450 amino acids, and δ approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, a constant region (CH) and a variable region (VH). In one form, the constant region is essentially identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. The heavy chains γ, α, and δ have a constant region consisting of three tandem Ig domains and a hinge region for added flexibility; the heavy chains μ and ε have a constant region consisting of four immunoglobulin domains. The variable region of the heavy chain is characterized by antibodies produced by various B cells, but is the same for all antibodies produced by a single B cell or a B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and consists of one Ig domain.

Mammals have two types of immunoglobulin light chain, designated λ and κ. The light chain has two consecutive domains: one constant domain (CL) and one variable domain (VL). The approximate length of the light chain is 211-217 amino acids. Each antibody contains two light chains that are always identical; however, only one type of light chain, κ or λ, is present in the antibody in mammals.

Although the overall structure of all antibodies is very similar, the unique property of a given antibody is determined by variable (V) regions, as described in detail above. More specifically, variable loops, three on each light (VL) and three on heavy (VH) chains, are responsible for binding to the antigen, i.e., for antigenic specificity. These loops are called hypervariable regions (CDRs). Since CDRs from both VH and VL domains contribute to the antigen-binding center of the antibody, it is the combination of the heavy and light chains, and not they alone, that determines the final antigenic specificity.

The term "antibody fragment" encompasses at least one antigen binding fragment as defined above and exhibits substantially the same function and specificity as the complete antibody from which the fragment is derived. Limited papain proteolytic cleavage cleaves the Ig prototype into three fragments. Two identical amino-terminal fragments, each of which contains one complete L-chain and approximately half of the H-chain, are antigen-binding fragments (Fab). A third fragment, similar in size, but containing a carboxyl terminal half of both heavy chains with their interchain disulfide bond, is a crystallized fragment (Fc). Fc contains carbohydrates, complement binding and FcR-binding sites. Limited pepsin cleavage yields a single F (ab ′) 2 fragment containing both Fab parts and a hinge region, including an H-H interchain disulfide bond. F (ab ') 2 is divalent for antigen binding. The disulfide bond F (ab ') 2 can be cleaved to obtain Fab'. In addition, the variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts are, for example, HCl or HBr salts. The basic salts are, for example, salts with a cation selected from alkalis or alkaline compounds, for example, Na +, or K +, or Ca2 +, or ammonium ion N + (R1) (R2) (R3) (R4), where R1-R4 are independently from another mean: hydrogen, an optionally substituted C1-C6 alkyl group, an optionally substituted C2-C6 alkenyl group, an optionally substituted C6-C10 aryl group, or an optionally substituted C6-C10 heteroaryl group. Further examples of pharmaceutically acceptable salts are described in Remington's Pharmaceutical Sciences 17th ed. Alfonso R. Gennaro (eds.), Mark Publishing Company, Easton, PA, USA, 1985 and Encyclopedia of Pharmaceutical Technology.

Pharmaceutically acceptable solvates are, for example, hydrates.

While it has been shown and described that this invention has various designs, the present invention may be modified and modified within the scope and spirit of this disclosure. For example, to deliver a fixed dose, the syringe pen 1, 80, 90 is preferably modified so that the maximum rotation of the dial when unscrewing during preparation of the syringe pen 1, 80, 90 for injection will correspond to a fixed dose. Such a fixed-dose syringe pen can eliminate the need for a digital label indicating the dosage and instead provides the user with prompts such as, for example, instructions and a visual metering indicator. This disclosure is therefore intended to cover any variations, applications, or transformations of the present invention using its basic principles. In addition, this disclosure is intended to cover such deviations from the present disclosure that arise from known or generally accepted practice in the technical field to which this invention relates.

List of Reference Items

1. assembled injection device for drug delivery in the form of a pen

2. cartridge holder

4. body or body

8. cartridge

10. piston

11. membrane

13. cartridge cap

14. removable cap

15. neck

16. injection needle

17. far end of cartridge holder

20. midbody

21. prop

22. lead screw

23. drive nut

24. digital drum

25. swing arm

26. clutch

27. compression spring

28. dosing head

29. inner drum

30. the outer surface of the digital drum

31. keys

32. keyways

33. screw thread

34. threaded stop

35. dog teeth

36. fingers passing in the near direction

37. thread on the drive nut

38. flexible arrow

39. long-running teeth of the swing arm

40. flange

41. short-range teeth of the swing arm

42. the pivot of the swing arm

43. fingers of the swing arm

50. dosing head skirt

51. hole

52. thread on the outer surface of the digital drum

53. end face of the dosing head

54. axially extending teeth on the coupling

55. installation pin

62. thread on the inside of the body

63. end of the thread on the digital drum

64. thrust surface

65. the hollow interior of the digital drum

67. screw threads inside the digital drum

70. notches

71. windows on the digital drum

72. ledges

73. assembly fingers

75. screw thread on the inner drum

76. teeth protruding along the axis on the inner drum

77. flanged nests

78. spikes

80. device with a spring mechanism

81. a separate component of the supporting surface

82. compression spring

84. the far end of the compression spring

86. proximal end of compression spring

90. device with a spring mechanism

92. wave spring

94. the far end of the wave spring

95. the near end of the support

96. proximal end of a wave spring

Claims (26)

1. The device (80, 90) with a spring mechanism for drug delivery, containing: case (4); a piston rod (22) having a longitudinal axis, a distal end and a proximal end and configured to move along the axis in the far direction relative to the housing (4), a middle body (20) fixed inside the body (4) and coupled to the piston rod (22) in such a way that the piston rod (22) is able to move along the axis in the far direction relative to the middle body (20), the pre-tensioned spring (82, 92) is functionally coupled to the piston rod (22) so that the spring (82, 92) is released, and the energy stored in the spring (82, 92) helps to drive the piston rod (22) into far direction with the introduction of a dose, characterized in that a pre-tensioned spring (82, 92) is functionally connected between the middle case (20) and the piston rod (22), and a pre-tensioned spring (82, 92) is functionally connected between the middle case (20) and the piston rod support (21) (22) . 2. The device (80, 90) according to claim 1, in which the pre-tensioned spring (82, 92) is functionally connected to a separate component (81) of the bearing surface attached to the proximal surface of the bearing (21). 3. The device (90) according to claim 1 or 2, in which the pre-tensioned spring is a wave spring (92). 4. The device (90) according to claim 3, in which the wave spring (92) is functionally connected with the proximal surface (95) of the support (21). 5. The device (80, 90) according to claim 1, in which the piston rod (22) includes a threaded rod and a support (21) is attached to the distal end. 6. The device (80, 90) according to claim 5, in which the piston rod (22) is fixed without rotation during exposure and dose delivery, and the middle housing (20) is configured to prevent rotation of the piston rod (22) relative to the housing (4). 7. The device (80, 90,) according to claim 6, further including: a drive nut (23), which is in threaded engagement with the piston rod (22) and is configured to screw movement along it; a digital drum (24), which is in threaded engagement with the housing (4) to ensure screw movement relative to the housing (4); while the rotary link (25) is connected to the drive nut (23) and is configured to move along the axis and is fixed without rotation relative to the drive nut (23), moreover, the swing arm (25) is fixed without rotation with a digital drum (24), when the swing arm (25) and the digital drum (24) are in the first axial configuration, and the digital drum (24) is able to rotate relative to the swing arm (25) when the swing arm (25) and the digital drum (24) are in a second axial configuration. 8. The device (80, 90) according to claim 7, in which the inner drum (29) is threadedly engaged with the digital drum (24), wherein the inner drum (29) is movable along the axis and fixed without rotation relative to the housing (four). 9. The device (80, 90) according to claim 8, in which the inner drum (29) is arranged to move along the axis and is fixed without rotation relative to the median body (20). 10. The device (80, 90) according to claim 1, in which the piston rod (22) has a smooth keyway (32) located parallel to the longitudinal axis; moreover the middle case (20) includes dowels (31), which are slidably inserted into the keyway (32). 11. The device (80, 90) according to claim 1, in which the middle body (22) further comprises at least one ratchet lever (38), preventing the propeller (22) from moving in the near direction. 12. The device according to any one of paragraphs. 7-11, in which the threaded engagement of the digital drum (24) with the housing (4) has a first step, the threaded engagement of the inner drum (29) with the digital drum (24) has a second step, and the thread of the threaded rod of the piston rod has a third step, the first step, second step and third step being different from each other. 13. The device according to any one of paragraphs. 7-11, in which, during the dose setting, the swing arm (25) and the digital drum (24) are in a first axial configuration in which the screw movement of the swing arm (25) and the digital drum (24) relative to the housing (4) unscrew the swing arm (25) and the digital drum (24) the first axial distance from the starting position, and this screw movement of the rotary link (25) screw the drive nut (23) along the threaded rod of the spindle by a second axial distance different from the first axial distance, while during to dose rates, the rotary link (25) and the digital drum (24) are in a second axial configuration in which the helical movement of the digital drum (24) relative to the housing (4) moves the inner drum (29) back to its original position without rotating in the far direction so to advance along the axis of the drive nut (23), which is fastened without the possibility of movement along the axis with the inner drum (29), and so that the piston rod (22) and the movable piston (10) protrude fluid from the outlet (17) cartridge.

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