Patent Application
20220280189
The present invention is in the field of injector systems for medical implants, in particular for drug-eluting medical implants.
The injection of a medical implant is typically via a subcutaneous, intramuscular, or intradermal injection route and entails advancing an implant loaded into a syringe along a bore of an injection needle into tissue of the patient. The implant may be any, for instance, a drug-eluting implant, a radio-opaque marker, encapsulated electronic device. Where the implant is drug-eluting, it typically elutes one or more active substances for a prolonged period, for instance, for the delivery of an LHRH agonist or antagonist (e.g. goserelin, leuprorelin or buserelin) for the treatment of hormone sensitive cancers such as breast or prostate cancers or for treatment of benign gynaecological disorders (e.g. endometriosis, uterine fibroids and endometrial thinning).
The diameter of the implant needs to be carefully controlled; it governs the forces required for injection. Regulating the diameter of the implant is paramount to proper storage and transport also. If the implant is greater than a specified dimensional tolerance, injection forces can be excessive and it can lead to damage of the implant. If the implant is smaller than a specified dimensional tolerance, the implant can drop out from a pre-loaded syringe during transport or during preparation by the administering physician. At the same time, it is desirable to minimise the diameter of the needle used to inject the implant. A larger diameter needle causes more pain to the subject, which in some cases requires a local anaesthetic; avoidance of administrating additional medication (e.g. opiates) is desirable. Further, a larger needle diameter increases trauma and healing time. In addition, an ability to easily adapt an injector to administer implant of different diameters and doses would lead to significant cost saving in manufacturing and seeking regulatory approval.
In U.S. Pat. No. 5,772,671, the implant is damaged by a plurality friction ribs that prevent the implant from falling out, but which damage the implant as it passes through (see
It is an aim of the present invention to provide an injector system that overcomes the problems of the art, and which maximises the range of implants deliverable by an injector system.
Described herein is an injector system (500) for injection by puncture of an organ, of a non-deformable medical implant (200) into a subject comprising:
Described herein is an injector system (500) for injection of a medical implant (200) into a subject comprising:
The injector system (500) may further comprising an injection needle assembly (400) in fluid connection with the exit port (104) of the holding element (100), which needle assembly (400) comprises a needle component (402) disposed with a bore (404) for the passage of the implant (200) wherein the compliant member assembly (150) is configured to align the implant (200) for passage through the bore (404). The number of compliant members (152) may be 2 or more. The compliant member assembly (150) may comprise 2, 3 or 4 compliant members (152) arranged in the compliant member assembly (150) to form an essentially circular profile. The compliant member assembly (150) may comprise an aperture defined by the compliant members (152), preferably by inward pointing edges of the compliant members (152), the aperture having a minimum width smaller than a minimum width of the implant (200) transverse profile. The compliant member assembly (150) may be biased in an essentially planar configuration. The compliant member assembly (150) may be disposed within the holding element (100), or, when the injection needle assembly (400) is present, within the needle assembly (400). The compliant member assembly (150) may be further configured as a compliant mechanical stop adapted to stop slidable entry of the implant (200) into the compliant member assembly (150) and through the exit port (104) under a force of gravity. The injector system (500) may be configured such that frictional engagement locks the position of the implant (200) relative to the compliant member assembly (150), wherein an injection force applied to the implant (200), preferably of less than 10 N, overcomes the lock. The injector system (500) may further comprising a syringe (300) having a syringe barrel (320), wherein the holding element (100) is disposed within the syringe barrel (320). The holding element (100) may be a syringe barrel (320). The injector system (500) may further comprise the implant (200). The injector system (500) may be configured for subcutaneous injection, intramuscular or intradermal injection of the implant (200). The injector system (500) may further comprising a needle protection mechanism.
Before the present system and method of the invention are described, it is to be understood that this invention is not limited to particular systems and methods or combinations described, since such systems and methods and combinations may, of course, vary. It is also to be understood that the terminology used herein is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.
As used herein, the singular forms “a”, “an”, and “the” include both singular and plural referents unless the context clearly dictates otherwise.
The terms “comprising”, “comprises” and “comprised of” as used herein are synonymous with “including”, “includes” or “containing”, “contains”, and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps. It will be appreciated that the terms “comprising”, “comprises” and “comprised of” as used herein comprise the terms “consisting of”, “consists” and “consists of”.
The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within the respective ranges, as well as the recited endpoints.
The term “about” or “approximately” as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/−10% or less, preferably +/−5% or less, more preferably +/−1% or less, and still more preferably +/−0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier “about” or “approximately” refers is itself also specifically, and preferably, disclosed.
Whereas the terms “one or more” or “at least one”, such as one or more or at least one member(s) of a group of members, is clear per se, by means of further exemplification, the term encompasses inter alia a reference to any one of said members, or to any two or more of said members, such as, e.g., any ≥3, ≥4, ≥5, ≥6 or ≥7 etc. of said members, and up to all said members.
All references cited in the present specification are hereby incorporated by reference in their entirety. In particular, the teachings of all references herein specifically referred to are incorporated by reference.
Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.
In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.
Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the appended claims, any of the claimed embodiments can be used in any combination.
In the present description of the invention, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration only of specific embodiments in which the invention may be practiced. Parenthesized or emboldened reference numerals affixed to respective elements merely exemplify the elements by way of example, with which it is not intended to limit the respective elements.
It is to be understood that other embodiments may be utilised and structural or logical changes may be made without departing from the scope of the present invention. The following detailed description, therefore, is not to be taken in a limiting sense, and the scope of the present invention is defined by the appended claims.
The terms “distal” and “proximal” are used through the specification, and are terms generally understood in the field to mean towards (proximal) or away (distal) from the user (e.g. physician) side of the apparatus. Thus, “proximal”, “proximally”, or “proximal to” means towards the user side and, therefore, away from the patient's side. Conversely, “distal”, “distally”, or “distal to” means towards the patient's side and, therefore, away from the user's side.
The present invention relates to an injector system for injection of a medical implant. The injector system comprises a holding element having a proximal and distal end disposed with a chamber for containing the implant. The holding element is disposed with an exit port at the distal end for slidable ejection of the implant. The injector system further comprises a compliant member assembly comprising at least one compliant member configured to frictionally engage the implant to impede passage past or through compliant member assembly. The compliant member assembly may be further configured to prevent entry by the implant therein under a force of gravity e.g. when the injector system is in transit. The compliant member assembly is disposed in fixed relation to the holding element. The implant is slidable relative to the compliant member assembly once engaged within the compliant member assembly. The invention maintains the implant in the holding element during transport and storage of the injection system. In addition it maintains the integrity of the implant after injection. The compliant member allows the implant to remain intact when passing through the compliant member assembly. Accordingly, the reliability of the delivery (dose delivered and duration of the release) is ensured.
The injection system is suitable for injection of an implant into a body of a subject, preferably a mammalian (e.g. animal), preferably a human subject. In particular, it is suited for subcutaneous injection, intramuscular or intradermal injection of an implant.
The medical implant, also referred to herein as implant may be any suitable for injection. It typically has a solid state i.e. not a liquid nor a gas. It may be essentially incompressible or non-deformable. By non-deformable, it is meant that the implant retains its shape and size under the application of force, in particular, under the application of forces experienced during injection. The implant may be dimensioned for implantation subcutaneously, intramuscularly, or intradermally. It preferably has an essentially cylindrical shape, though other shapes are envisaged such as those having oval, C-shaped, or polygonal profile. It may have rounded or flat ends. It is preferably longitudinal. A longitudinal direction of the implant may be generally aligned with longitudinal directions of the holding element chamber, and needle bore. It may be made from a bio-compatible material. The medical implant has a general profile that is a transverse cross section i.e. a section perpendicular to a longitudinal axis of the implant. Where the medical implant is cylindrical, the general profile is circular.
The implant may be provided with one or more active pharmaceutical ingredients. The implant may be configured for the slow release of one or more active pharmaceutical ingredients. An active pharmaceutical ingredient may be, for instance, an LHRH agonist or antagonist. An active pharmaceutical ingredient may be Buserelin, Triptorelin, Leuprorelin, Goserelin, Deslorelin, Histerlin, Avorelin, Nafarelin, Lutrelin, Cystorelin, Gonadorelin, Detirelix, or Luliberin. The implant may be provided with a combination of one or more of the aforementioned active pharmaceutical ingredients The implant may be biodegradable. The implant may be formed essentially from a biodegradable polymeric material, such as poly(α-esters), polyurethane, poly(ester amide), poly(ortho esters), polyanhydrides, polyphosphoester.
The implant may comprise an electronic device. It may comprise one or more electronic sensors, one or more radio-frequency transmitters, one or more radio-frequency receivers. The electronic components may be encapsulated in a non-biodegradable polymeric material.
The implant may be radio-opaque and act as a medical imaging marker.
The holding element is disposed with a chamber for containing the implant. The holding element has a body, typically formed from a rigid material such as polycarbonate or polypropylene, styrenics polymer (ABS-acrylonitrile butadiene styrene), ABS, cyclic olefin copolymer, polyethylene or polyolefin plastics. The body may be longitudinal. The body may be essentially cylindrical or frustoconical. The holding element has a proximal and distal end. The holding element has a chamber dimensioned for containing the implant. The chamber is preferably dimensioned to contain the entire implant. The chamber is preferably dimensioned to contain an entire axial length of the implant. The chamber is used to store the implant so that the injector system can be supplied to the user ready for use. The holding element may not form a part of the needle assembly.
The holding element may be disposed within a syringe barrel as shown, for instance in
The distal end of the holding element is disposed with an exit port for passage of the implant. The exit port is an opening in the body of the holding element, disposed at the distal end, typically the distal terminal end. The exit port is configured for slidable ejection of the implant therethrough. Accordingly the exit port is larger than the maximum profile of the implant. The exit port may be smaller than a transverse cross-sectional profile of the holding element chamber. The system, more preferably the holding element is configured such that the exit port can communicate with a needle assembly. In particular the exit port aligns with a bore of a needle such that the implant passing through the exit port enters the needle bore. A central axis of the exit port may be co-axial with a central axis of a needle bore.
The holding element may comprise a coupling for attachment to a needle assembly. Where the holding element is contained within a barrel of a syringe, the syringe tip (e.g.
The proximal end of the holding element is disposed with an entry port for passage of a plunger deployment rod. The entry port is an opening in the body of the holding element, disposed at the proximal end, typically the proximal terminal end. The plunger deployment rod is slidable relative to the entry port, and displaces the implant by the application of an axial force. More specifically the plunger deployment rod is configured to apply an axial force to the implant for ejection from the chamber. The entry port is larger than the maximum profile of the plunger deployment rod.
The needle assembly may be disposed distal of the holding element. The needle assembly is attached to or attached with respect to the holding element such that the implant can pass from the chamber and through the needle bore upon deployment. The attachment in respect of the holding element may be direct attachment, or an indirect attachment, for instance, via one or more adapters. The needle assembly may be repeatably dismountable with respect to the holding element. It may be essentially permanently attached with respect to the holding element. A transverse cross-section of the bore may be smaller than a transverse cross-section of the holding element.
The needle assembly comprises a needle component for puncture of an organ, for instance, skin or muscle. The needle is typical of a syringe needle of the art, having a longitudinal form, sharpened at one end for puncture of the skin, and containing a bore connecting the distal end of the needle component to the proximal end of the needle component. When attached to the holding element, connection is made between exit port and the proximal end of the bore of the needle component. The needle bore is dimensioned for the passage for the implant. The needle is configured for a subcutaneous, intramuscular, or intradermal injection route.
The needle assembly may further comprise a coupling component (e.g. hub) for attachment of the needle component to or with respect to the holding element. The attachment to or with respect to the holding element refers to a direct attachment, or to an indirect attachment, for instance, via one or more adapters or via a syringe barrel in which the holding element is placed (e.g.
The system further comprises a compliant member assembly, comprising one or more compliant members, configured to receive the implant. The compliant member assembly is configured for the passage of the implant therethrough. The compliant member assembly has a through-passage connecting a distal side of the compliant member assembly to its proximal side. The compliant member assembly (150) has a biased (resting) state in which the at least two compliant members (152) additively form a partial or total occlusion of the through-passage. The compliant member assembly acts as a barrier between the chamber and the exit port. It is configured to frictionally engage the implant to impede passage therethrough. The compliant member assembly retains the implant at least partially within the holding element. The injector system preferably contains only one compliant member assembly.
The compliant member assembly is configured to frictionally engage the implant thereby impeding passage therethrough. Preferably, the compliant member assembly frictionally engages with the implant when the implant passes into and through the through-passage under an injection force. By frictionally engaged, it is meant that the compliant member assembly applies a frictional force to the implant as seen for instance in
Typically, frictional engagement arises during injection. The compliant member assembly is configured to retain the implant at least partially within the holding element by apply a retaining or frictional force to the implant.
The compliant member may be further configured as a compliant mechanical stop or mechanical stop. It prevents passage of the implant through the compliant member assembly under gravity. This stop functionality arises during transport of the injector system containing the implant, typically when the implant is not engaged with the compliant member assembly as shown, for instance, in
The compliant member assembly may be fixed in relation to holding element (as shown for instance in
The compliant member assembly may contain at least one compliant member biased to block passage of the implant therethrough (e.g.
The compliant member assembly may comprise 1, 2, 3 or 4 or more compliant members, preferably 2, 3 or 4 compliant members. Each compliant member may have a similar shape and/or size. Two or more compliant members may have a similar shape and/or size. One or more compliant member may have a different shape and/or size from the remainder of the compliant members. Each compliant member projects, preferably radially (optionally perpendicularly ±10 deg), towards a central axis of the injector system, holding element or needle assembly coupling component. Each compliant member project perpendicularly ±10 deg, to a central axis of the injector system, holding element or needle assembly coupling component. The compliant members may be arranged in the compliant member assembly to form an essentially circular profile i.e. outer shape. The compliant members may be circular or annular segments, preferably of the same size and shape, arranged as segments within a circle or annular ring. The 1, 2, 3 or 4 or more compliant members in the biased state may additively form a partial or total occlusion of the through-passage. By additively, it is meant that the size or footprint of each compliant member additively combines to form the extent of the occlusion. The compliant member assembly may comprise an aperture defined by the compliant members, preferably by inward pointing edges of the compliant members, having a minimum width (e.g. diameter) smaller than the minimum width (e.g. diameter) of the implant. The minimum width of the implant is measure across a transverse cross section i.e. a section perpendicular to a longitudinal axis of the implant.
The compliant members may be attached at the circle or annular ring periphery to the holding element, or to the needle assembly, or to the coupling component. The segmented compliant members may be attached at the circle or annular ring periphery to the wall of the holding element chamber, preferably towards the distal end, or to the wall of the needle bore, or more preferably incorporated into a coupling component of the needle assembly.
The compliant member assembly may be configured to align the implant with the exit port or with the bore of the needle component. For instance, it may essentially co-axially align a longitudinal axis of the implant with a central axis of the exit port. The compliant member assembly may be configured to align the implant with the bore of the needle. For instance, it may essentially co-axially align a longitudinal axis of the implant with a longitudinal axis of the needle bore. Alignment may be achieved, for instance, by disposing the compliant members so that forces applied by the compliant members act in a net radial direction on the implant to align it with a longitudinal axis of the needle bore and/or with the central axis of the exit port. For instance, the compliant members may be arranged evenly around a periphery or circumference of the bore, and/or be diametrically or symmetrically opposed.
A compliant member may be made from any suitable compliant material i.e. a material that has an inherent spring-like quality or that can adopt a spring-like form. Examples of suitable materials include polypropylene, silicone rubber, nitinol, polyethylene (PE), thermoplastic elastomer (TPE), polyacetal (POM).
Advantageously, the invention improves the reliability of the injector system, preventing unwarranted loss of the implant prior during storage or transport. It has been found that the use of a compliant member assembly does not increase the injection force required by the user compared with a standard injector. The injection force reflects the amount of effort needed by the user to advance the implant though the holding element chamber and needle. Further, the invention reduces or prevents deformation of the implant. The compliant member allows the implant to remain intact when passing through the compliant member assembly. Accordingly, the reliability of the delivery (dose delivered and duration of the release) is improved. Compared with non-compliant ribs, the injector of the invention reduces injection force, and significantly reduces the injection forces needed for larger implant sizes.
By aligning the implant with the needle bore, the compliant member assembly allows a decrease in the dimensional tolerance of the implant. In other words, the same injector system can be used with an implant manufactured with less-stringent dimensional uniformity, in particular in the transverse cross-section. By moving the location of the retaining mechanism (compliant member assembly) out from the needle bore i.e. distal of it, the size of the needle can be reduced, thereby reducing trauma and pain during injection.
For some applications, the injector system including the implant may be required to be supplied in a sterile state. The dimensions of the implant in particular of the transverse cross-section can be altered (e.g. size expansion or contraction) by the sterilisation process. Because the injector system contains one or more compliant members, these dimensional changes to the implant can be accommodated, and without a significant increase in injection force. Hence, the implant having a starting dimension will not fall out of the injector system before sterilisation and will still be able to pass through the compliant member assembly having expanded after sterilisation. The method for sterilization of maybe any, for example heat, gaseous technique or gamma irradiation. The gamma irradiation is preferred.
For other applications, different sizes of implant transverse profile may be available depending on the length of release time of an active pharmaceutical agent; the same injector system may be used for different implant sizes with a similar centering and retaining functionality, and without a significant increase in injection force.
An injector system for injecting an implant into a subject (e.g. subcutaneously, intramuscularly, or intradermally) was prepared comprising a holding element contained inside a syringe barrel, the holding element containing the implant, the system being provided without the compliant member assembly. Eleven such systems were prepared, and each system was to be tested in trials for implant injection effort. The length and diameter of implants were comparable with each other and suitable for placement in the injection system. The length of each of the implants was 1.3 cm, the diameter of each of the implants was 0.118 cm. Each implant was made of polymer containing an active pharmaceutical ingredient.
For each of the injector systems without the compliant member assembly, the implant dropped out from the injector at the beginning of the trial or when installing the injector systems on the apparatus for testing. Three implants were lost during trial. On the eight implants remaining, seven had a diameter smaller than the lower tolerance limit and passed through the needle under the force of gravity. The last remaining sample was at minimum limit of tolerance and dropped out of the injector upon contact with the shaft. The test protocol described in Experiment 2 was hence not completed due to loss of the implant.
An injector system for injecting an implant into a subject (e.g. subcutaneously, intramuscularly, or intradermally) was prepared comprising a holding element contained inside a syringe barrel, the holding element containing the implant, the system being provided without the compliant member assembly. The injector system was provided with one or more rigid ribs to prevent unwarranted exit of the implant. The ribs were disposed in the needle assembly hub. Four different designs of ribs (A to D) were used as portrayed in
The length of each of the implants was 1.3 cm, the diameter of each of the implants was 0.118 cm. Each implant was made of polymer containing an active pharmaceutical ingredient. The length of each rib was 0.02 cm in the direction of the central axis of the needle. The ribs were arranged to contact the implant; the maximum passage diameter through the ribs was less than the minimum diameter of the implant. Five such systems were prepared, and each system was tested in trials for implant injection effort. Injection effort was measured as follows: The injection system was placed vertically, with needle downwards, on a testing machine equipped with a clamping mechanism to retain the injection system in a fixed position. The syringe was advanced at a speed of 100 mm/min, and the maximum effort (force) applied over time to fully eject the implant was measured. The results are given in the Table 1 below. The ribs damage the implant after injection or the force needed to eject the implant is very high.
An injector system for injecting an implant into a subject (e.g. subcutaneously, intramuscularly, and/or intradermally) was prepared comprising a holding element contained inside a syringe barrel, the holding element containing the implant, the system being provided with the compliant member assembly of the invention. The compliant member assembly was disposed in the needle assembly hub. Exemplary design of compliant member assembly is shown in
An injector system for injecting an implant into a subject (e.g. subcutaneously, intramuscularly, and/or intradermally) was prepared comprising a holding element contained inside a syringe barrel, the holding element containing the implant, the system being provided with the compliant member assembly of the invention. The compliant member assembly was disposed in the needle assembly hub. Exemplary design of compliant member assembly is shown in
| Number | Date | Country | Kind |
|---|---|---|---|
| BE2019/5555 | Aug 2019 | BE | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/073764 | 8/25/2020 | WO |
