JP2020121157A - Accurate dose control mechanisms and drug delivery syringes - Google Patents

Abstract

To provide dose control mechanisms which allow accurate dosing and delivery of medications.SOLUTION: A dose control mechanism 510 for a syringe 500 includes an engaging screw thread arrangement between an exterior surface of a plunger 514 and a longitudinally extending channel 520D of a housing 520. The engaging screw thread arrangement includes at least one thread segment 514B, and a pitch guide including a variable pitch thread. At least a portion of the longitudinally extending channel of the housing includes one of the pitch guide and the at least one thread segment, and the plunger includes the other of the pitch guide and the at least one thread segment. The plunger resides at least partially within the housing with the at least one thread segment engaged with the pitch guide.SELECTED DRAWING: Figure 8A

Description

The present invention relates to a precise dose drug delivery syringe. More particularly, the present invention relates to precise dose control mechanisms, drug delivery syringes incorporating such control mechanisms, methods of operating such devices, and methods of assembling such devices.

Injection methods adopted by physicians, inability to accurately read and control the amount of movement of the plunger during administration, and the dosage associated with the priming step used to deflate the syringe prior to the administration step. Various studies have shown that the accuracy of drug delivery is affected by many factors, including a decrease in These effects are especially associated with drug delivery syringes having a high dose volume to axial translation ratio (i.e. even with progressively smaller plunger depressions, as may be the case with large diameter syringes). , A significant amount of drug is administered), and this problem is exacerbated when delivering microliter scale doses. Although these causes for negligence are common, accurate dose syringes are still needed. These syringes are especially important for high precision operations such as intravitreal injections, and for low dose treatments where incorrect administration can result in substantial negligence and potential harm to the patient. , Very desirable.

Depending on whether the physician chooses to deliver 5 μL (microliters) of the therapeutic agent by pressing the syringe plunger from 10 μL to 5 μL or by pressing the syringe from 5 μL to 0 μL Studies have shown that the amount of therapeutic agent taken can vary significantly. In addition, the uncertainty of the plunger's travel limit may cause some physicians to push the syringe beyond its natural travel limit, causing excessive compliance with the patient due to mechanical compliance between the stopper and syringe barrel. May be delivered. For example, given the particular syringe barrel diameter, the physician may depress the plunger beyond the natural stop for 0 μL and may incorrectly deliver a dose up to 20% more than needed. This error is magnified by the small dosing volume requirements for certain therapeutic agents. Due to the small dose and associated travel distance of the plunger, it is very difficult for the physician to measure the fill volume of the dosing chamber and control the injection volume as the therapeutic agent is delivered to the patient. .. This inaccuracy in dosing can result in substantial safety risks, including increased pressure in the target area and altered (reduced) drug efficacy, among other side effects. ..

A major source of dosing inaccuracy is the inability to reliably set the limit of plunger travel and the inherent variability of dosing during delivery such that the plunger seal (or stopper) is depressed at the end of delivery. There is. Also, possible variations in the placement of the reference marks on the syringe barrel during syringe manufacture also contribute to the inaccuracy. Unique to these sources of inaccuracy is that, as mentioned above, the delivered volume is very sensitive to the axial displacement of the plunger. However, mechanical travel limits are difficult to employ in such applications due to the difficulties associated with reading and controlling the plunger travel by the user over small dosing distances. Briefly, the dosage is so small that it is difficult for the physician to see the dosage measurement in the syringe barrel during injection and accurately control the plunger depression and dosage.

In addition to improving dosing accuracy, it is useful to incorporate the functionality of a priming step into the syringe design to reduce or eliminate air bubbles within the dosing chamber. This step is very useful for minimizing safety risks, improving operational hygiene and reducing pressure at the target site. Minimizing the potential for air bubbles during filling helps simplify the drug delivery process for clinicians. Employing drug-filled syringes (prefilled syringes) can help minimize air bubbles. However, even drug-filled syringes are not completely devoid of air trapped during the filling process.

Thus, a syringe that allows the user to easily confirm and control the dosage, minimize the presence of bubbles in the dosing chamber prior to drug delivery, and ensure accurate delivery of the required drug dosage. But is substantially needed. With such a syringe, it is preferable to take advantage of the benefits associated with the use of such products in pre-filling.

Moreover, some pharmaceuticals require the mixing of the two fluids or the reduction of the dried or lyophilized drug prior to injection of the correct dose. This allows, for example, immediately before injection, a diluent to be added to the dehydrated, lyophilized, dried or powdered active substance, which deteriorates when stored in its hydrated form. It is especially useful for substances that tend to lose activity. This also allows the mixing of the two liquids, which are mixed just prior to injection.

Although it is known to provide a syringe with a mixing device that mixes deliverables prior to injection, the marketplace requires the delivery of accurate dosages as required for some pharmaceuticals and as described above. It is not possible to provide such a mixed syringe that can be provided. Examples of such mixing syringes are disclosed, for example, in US patent application Ser. No. 13/566,079, assigned to the assignee of the present disclosure and incorporated herein by reference. In addition to the complexity of the structure itself, the design may require complex assembly, multiple operating steps by the user, or certain other subtle differences that make them difficult to manufacture, assemble, or operate. There is. Furthermore, some mixing syringes must also deal with such things as maintaining the sterility of the container, the interaction of components for sealing, evacuation requirements, and distribution of internal forces, among others. Each of these challenges is further compounded when extreme dose accuracy is required.

The present invention provides a dose control mechanism that enables accurate dosing and delivery of drug therapeutics and drug delivery syringes incorporating such control mechanism. These new devices allow confirmation and control of dosage within a device size similar to commonly used conventional syringes all available on the market, and “priming” the syringe prior to drug delivery (ie , Air bubbles) and ensure accurate delivery of microliter volume doses. These novel devices are safe and easy to use, and are aesthetically and ergonomic to clinicians without significantly changing the techniques currently employed to administer injectable pharmaceuticals by clinicians. Attractive. The novel device of the present invention provides these desirable features without any of the problems associated with known prior art devices.

In a first embodiment, the present invention provides a dose control mechanism for a syringe. The control mechanism includes a plunger having a coarse thread on an outer surface, a housing having a corresponding coarse guide along an inner surface, and a screw having a fine thread for engaging a fine nut of an adapter, the plunger having a thread at least partially. Has an internal annular space that exists in a natural manner. Plungers having a coarse line are rotatable on corresponding coarse line guides, and at least a portion of the plunger is rotationally tightened to mate with a corresponding rotational fastening portion of the screw. The pitch ratio between the coarse and fine threads is from about 1:1 to about 20:1, more specifically from about 2:1 to about 10:1, more preferably from about 4:1 to about. 8:1. In the preferred embodiment, the pitch ratio between coarse thread 14B and fine thread 30B is about 4:1. The screw may further include a screw connection aspect and optionally a ring that functions to connect the screw directly to the plunger seal or to the plunger rod. In at least one embodiment, the housing has a housing cover at its proximal end and a window that allows a user to identify the position of the plunger within the housing. The plunger can have one or more dose marks on the outer surface of the plunger and the housing can have one or more guide marks to align the plunger dose mark. When used by the user, the plunger translates axially for a first distance D1, and translates the screw axially for a second distance D2, where D1 is always greater than D2 by a factor determined by the pitch ratio. ..

In a second embodiment, the present invention provides a precise dose drug delivery syringe having a dose control mechanism, a barrel, a plunger seal, and a barrel adapter assembly having a barrel tip and a needle. The syringe may further include a plunger rod having one end connected to the screw and another end connected to the plunger seal. The syringe can be a point-of-use syringe, a drug-filled syringe or a safety syringe, or a combination thereof. The housing of the syringe may have a housing cover at its proximal end to protect the interior of the housing from the environment and a window that allows the user to locate the plunger within the housing. it can. The plunger can have one or more dose marks on the outer surface of the plunger, and the housing can have one or more guide marks on the window to align the plunger dose marks. When used by the user, the plunger translates axially a first distance D3 and translates the screw axially a second distance D4.

The dose control mechanism can also be designed to provide the desired axial movement of the screw relative to the axial movement of the plunger. In other words, the dose control mechanism can be adapted to provide the desired feel to the user by the plunger while providing the desired axial movement of the screw and the associated dosing of the medication. In an embodiment, the plunger and housing are connected to each other by a variable pitch screw. The pitch can vary over the length of travel of the plunger with respect to the housing, or the travel can include two or more distinct or transitional pitches. However, in each case, the variable pitch provides at least two pitches.

In an embodiment, for example, the housing includes at least one variable pitch thread along its inner diameter and the plunger has at least one thread segment arranged to engage the variable pitch thread of the housing. Including. According to a preferred embodiment, the variable pitch thread of the housing comprises a fine thread towards its proximal end and a coarse thread towards its distal end. Thus, if the user applies a substantially constant velocity movement of the plunger when depressing the plunger, as the thread segment of the plunger moves along the fine line, the plunger and the interlocking screw will move at a first velocity. , While the plunger and interlocking screw rotate at a slower speed as the thread segment of the plunger engages a coarse thread located toward the tip of the housing. Thus, rotation of the plunger and associated screw can be adapted to a wide range of rotational speeds, and thus axial movement of the screw, by utilizing the variable pitch screw engagement between the plunger and the housing. ..

As mentioned above, the fine pitch portion of the variable pitch thread may have a 1:1 pitch ratio with the thread of the adapter, and the coarse portion of the variable pitch thread may have a maximum of about 20: It can have a ratio of 1.

Variable pitch threads can offer many advantages. For example, the syringe can be configured to be filled at the time of use. The variable pitch allows the syringe to be filled more quickly.

The housing can be provided in one or more components. Merely by way of example, the housing may include more than one housing portion with respective pitch threads, which may provide advantages with respect to the manufacturing process. As a further example, the housing may include a lower housing portion having a seam and an upper housing portion having a finer stitch. The components of the housing can be assembled by any suitable coupling configuration including, but not limited to, spin welding, adhesives, or coupling structures such as threads or engagement latches.

In another embodiment, the dose control mechanism further comprises a housing including a first housing portion and a second housing portion movable relative to each other. For example, the second housing portion can be located between the first housing portion and the plunger. In such an embodiment, the second housing portion includes an internal thread, which may be either constant pitch or variable pitch, configured to engage the external thread segment of the plunger. The second housing portion is, in the first configuration, configured to be axially translatable with respect to the first housing portion. In the second configuration, the second housing part is fixed with respect to the first housing part. As described below, this allows the syringe to be rapidly filled and primed in a manner familiar to the user while providing precise dose control during delivery.

According to one aspect of the invention, there are provided a dose control mechanism for a syringe and a syringe including such a dose control mechanism. One example of such a dose control mechanism includes a housing, an adapter, a plunger and a screw. The housing includes a longitudinally extending channel having an inner surface. The adapter includes a channel having fine threads. The plunger has an outer surface and an axially extending channel, the axially extending channel including the first key feature. The screw includes a screw outer surface, the screw outer surface including a second key feature along a proximal portion of the screw outer surface. The proximal end of the screw is at least partially disposed within the axially extending channel of the plunger. At least a portion of the second key aspect is disposed within the axially extending channel of the plunger and engages the first key aspect for sliding movement, whereby rotational movement of the plunger causes rotation of the screw. Transfer is brought. The tip portion of the outer surface of the screw includes a fine thread that is at least partially disposed within and interlocks with the fine thread of the adapter. An engagement thread configuration is provided between the plunger and the housing. The engagement thread configuration includes at least one thread segment and a pitch guide including a variable pitch thread. At least a portion of the longitudinally extending channel of the housing includes one of the pitch guide and the at least one thread segment, and the plunger includes the other of the pitch guide and the at least one thread segment. The plunger resides at least partially within the housing with at least one thread segment engaged with the pitch guide. In at least one embodiment of the dose control mechanism, the variable pitch thread comprises at least two different thread pitches. In at least a further embodiment, the variable thread pitch varies continuously along at least a portion of the variable thread pitch.

At least a further embodiment of such a dose control mechanism includes a housing, an adapter, a plunger and a screw, the housing having a longitudinally extending channel having an inner surface and relative to each other between a retracted position and an extended position. And at least a first housing portion and a second housing portion arranged for telescopic movement. The adapter includes a channel having fine threads. The plunger has an outer surface and an axially extending channel, the axially extending channel including the first key feature. The proximal end of the screw is at least partially disposed within the axially extending channel of the plunger. The screw has a threaded outer surface including a second key feature along the proximal portion. At least a portion of the second key aspect is disposed within the axially extending channel of the plunger and engages the first key aspect for sliding movement, whereby rotational movement of the plunger causes rotation of the screw. Transfer is brought. The tip portion of the outer surface of the screw includes a fine thread located at least partially within the fine thread of the adapter and engaging the fine thread. An engagement thread configuration is provided between the outer surface of the plunger and the housing. The engagement thread configuration includes at least one thread segment and a pitch guide including the thread. At least a portion of the longitudinally extending channel of the housing includes one of the pitch guide and the at least one thread segment, and the plunger includes the other of the pitch guide and the at least one thread segment. The plunger resides at least partially within the housing with at least one thread segment engaged with the pitch guide. According to at least one embodiment, the first housing and the second housing are arranged to move between a retracted position and a priming position. According to at least one embodiment, when the first housing part and the second housing part are nested relative to each other between the retracted position and the extended position, a rotational movement therebetween is possible.

Further, in at least one embodiment, the dose control mechanism comprises a dose feedback mechanism. The feedback mechanism may provide tactile feedback to the user for confirmation of the desired delivery volume, for example. The user feels a tactile notch or stop when dialing the plunger rod/screw to his or her desired dosing volume (ie, confirming the desired microliter setting in the window), and thus the desired Know that you should determine whether you have reached your dose volume. The feedback mechanism can include multiple volume-based detents, for example, as shown when the syringe is at a delivery volume of 20 microliters, 10 microliters and 5 microliters. In one embodiment, one or more clips can be attached to the housing to engage the plunger rod/screw at an axial position that corresponds to one or more desired set/stop points. The clip can have, for example, one or more radially inwardly extending projections that extend through corresponding apertures in the housing at the threaded portion of the housing. The clip protrusions are configured to removably engage or contact one or more corresponding recesses, recesses, apertures, etc. of the plunger rod/screw. When the user axially rotates the plunger rod/screw to his desired delivery volume, the clip projection contacts/engages the threaded recess corresponding to the defined set/stop point. The set point/stop point recesses are each sized to match the amount of drug volume in the syringe for drug delivery. Therefore, multiple clips including clip protrusions are used to provide various tactile feedback along the axial length of the plunger rod/screw to provide the user with one or more tactile feedbacks regarding the dialed dose volume within the syringe. A plurality of apertures can be engaged with the housing to engage the plunger rods/screws in various set point recesses. In another embodiment, the clip protrusions can be pre-established and shaped as a radially inner aspect on the housing.

In a further embodiment, a method of manufacturing a syringe with a control mechanism includes: (i) attaching a barrel adapter assembly to the tip of a syringe barrel; (ii) attaching a plunger seal through the proximal end of the syringe barrel; (Iii) attaching a control mechanism to the proximal end of the syringe barrel, where the control mechanism may remain in contact with the plunger seal. The method may further include the step of (ii) at least partially filling the barrel with a fluid substance prior to the step of attaching the plunger seal through the proximal end of the syringe barrel. In at least one embodiment, the adapter is a two component adapter having a proximal adapter portion and a distal adapter portion. The proximal adapter portion has one or more connecting lugs, the distal adapter portion has corresponding connecting holes, and the connecting lugs and corresponding connecting holes engage and mate when pressed together. Mating or otherwise connecting to integrate the two parts of the adapter. Steps (i) and (ii), and the optional step of filling the barrel at least partially with a fluid substance, can be performed in a sterile environment to maintain container integrity and sterility of the syringe.

The invention further provides methods of assembling a dose control mechanism, methods of making a syringe having a dose control mechanism, and methods of operating such a mechanism and syringe. These novel devices and methods allow for dose confirmation and control, all within the same device size as commonly used conventional syringes available on the market, "priming" syringes prior to drug delivery. (Ie, air bubbles can be removed), ensuring accurate delivery of microliter volumes of medication. Throughout this specification, unless stated otherwise, related terms such as “comprising” or “comprising” or “consisting of” are used inclusively and not exclusively, whereby the described whole or A whole group may include one or more other undescribed whole groups or whole groups. As described further below, embodiments of the present invention can include one or more additional components that can be considered standard components in the medical device industry. These components and embodiments containing such components are to be understood as being within the contemplation of the invention and within the breadth and scope of the invention.

The following non-limiting embodiments of the present invention will now be described with reference to the following drawings.

FIG. 1(a) shows a side elevation view of a dose control mechanism according to at least one embodiment of the present invention, and FIG. 1(b) shows the dose control mechanism axis “A” of FIG. 1(a). A cross-sectional view is shown on a plane "B" that is perpendicular to the plane. FIG. 2(a) shows a cross-sectional view of the dose control mechanism shown in FIG. 1A so that the components can be seen in the ready-to-inject stage of operation, and FIG. 2(b) shows the components at the end-of-dose stage of operation. As can be seen, there is shown a cross-sectional view of the dose control mechanism shown in FIG. 3(a) shows an exploded view of the dose control mechanism shown in FIG. 1(a) taken along the axis "A", and FIG. 3(b) shows the dose control shown in FIG. 1(a). FIG. 6A shows a cross-sectional exploded view taken along the axis “A” of the mechanism. FIG. 4(a) shows an isometric view of a drug delivery syringe incorporating a dose control mechanism according to the second embodiment of the present invention, and FIG. 4(b) shows the tip of the drug delivery syringe shown in FIG. 4(a). Figure 3 shows an enlarged isometric view of a portion. 5(a) shows an isometric view of another drug delivery syringe incorporating a dose control mechanism according to another embodiment of the present invention, and FIG. 5(b) shows the drug delivery syringe shown in FIG. 5(a). 3 shows an enlarged isometric view of the tip portion of FIG. Figure 6(a) shows an isometric view of yet another drug delivery syringe incorporating a dose control mechanism according to another embodiment of the invention, and Figure 6(b) shows the drug delivery shown in Figure 6(a). Figure 3 shows an enlarged isometric view of the tip of the syringe. FIG. 7A(a) shows an isometric view of an initial assembly stage of a drug-loaded drug delivery syringe incorporating a dose control mechanism according to at least one embodiment of the present invention, and FIG. 7A(b) shows FIG. 7A(a). FIG. 4A shows an isometric view of the drug-filled drug delivery syringe shown in FIG. FIG. 7B(c) shows an isometric view of the drug-filled drug delivery syringe shown in FIG. 7A(a) at the ready-to-injection stage of the operation, and FIG. 7B(d) shows FIG. FIG. 7 shows an isometric view of the drug-filled drug delivery syringe shown in a). FIG. 9 shows a cross-sectional view of an alternative design of the dose control mechanism so that the components can be seen in the ready-to-inject stage of operation. FIG. 8B illustrates a cross-sectional view of the dose control mechanism shown in FIG. 8A so that the components can be seen in the ready-to-inject stage of operation. FIG. 8B shows a cross-sectional view of the dose control mechanism shown in FIG. 8A so that the components can be seen at the end of administration stage of operation. 9(a) shows an exploded view of the dose control mechanism shown in FIGS. 8A-8C taken along the longitudinal axis, and FIG. 9(b) shows the dose control mechanism shown in FIGS. 8A-8C. Figure 3 shows an exploded cross-sectional exploded view along the longitudinal axis of the. 10A(a) is a cross-sectional view of a syringe incorporating another embodiment of a dose control mechanism according to the present invention, with the housing shown in an extended position, and FIG. 10A(b) of FIG. 10A(a). FIG. 7 is a side elevational view of the syringe. 10B(c) is a cross-sectional view of the syringe of FIGS. 10A(a) and 10A(b) in the priming position, and FIG. 10B(d) is in the position shown in FIG. 10B(c). 10B is a side elevational view of the syringe of FIG. 10A(b). FIG. 10C(e) is a cross-sectional view of the syringe of FIGS. 10A(a)-10B(d) upon completion of delivery, and FIG. 10C(f) is in the position shown in FIG. 10C(e). 10B(d) is a side elevational view of the syringe of FIG. Figure 11(a) is an exploded view of the dose control mechanism of Figures 10A(a)-10C(f), exploded along the longitudinal axis, and Figure 11(b) is along the longitudinal axis. FIG. 12A is a cross-sectional assembly exploded view of the dose control mechanism shown in FIGS. 10A(a) to 11(a), which has been disassembled. 12A(a) is a side elevational view of another embodiment of a dose control mechanism according to the present invention with the housing shown in a retracted position, and FIG. 12A(b) is the dose of FIG. 12A(a). FIG. 6 is a side elevational view of the control mechanism with the housing shown in an extended position. 12B(c) is a side elevational view of the dose control mechanism of FIGS. 12A(a) and 12A(b) in a priming position, and FIG. 12B(d) is in a ready position for delivery. 12A(a)-12B(c) is a side elevational view of the dose control mechanism of FIG. 12B(e), FIG. 12B(e) is the side of the dose control mechanism of FIGS. 12A(a)-12B(d) during delivery. It is an elevation view. FIG. 12A is an enlarged partial isometric view of the engagement of the first housing portion and the second housing portion of FIGS. 12A(a)-12B(f) in the retracted position shown in FIG. 12A(a). , Partially transparent to illustrate the internal structure. FIG. 12A is an enlarged partial isometric view of the engagement of the first housing portion and the second housing portion of FIGS. 12A(a)-12B(f) in the extended position shown in FIG. 12A(b), where the first housing portion is , Partially transparent to illustrate the internal structure. FIG. 12B is an enlarged isometric view of the engagement of the first housing portion and the second housing portion of FIGS. 12A(a)-12B(f) in the delivery position shown in FIG. 12B(e), where the first housing portion is , Partially transparent to illustrate the internal structure. FIG. 14A is an enlarged isometric view of the second housing portion of the embodiment of FIGS. 12A(a)-13C. FIG. 6 is an enlarged partial cross-sectional view of an embodiment of an engagement structure between a first housing portion and a second housing portion according to an embodiment of the present invention. FIG. 16(a) is a side elevational view of a syringe incorporating a dose control mechanism according to another embodiment of the present invention incorporating a tactile feedback function, and FIG. 16(b) is a diagram illustrating the tactile feedback function. FIG. 17 is a side elevation partial cross-sectional view of the partially cut-away syringe of FIG. 16( b ), and FIG. 16( c) is an enlarged view of the cross-sectional portion of FIG. 16( b ).

The term “axial” or “axially” as used herein to describe any of the relative positions of dose control mechanisms, drug delivery syringes, components of the invention is generally , Refers to the longitudinal axis "A", and the control mechanism and syringe are preferably centered about it, but are not necessarily symmetrical about it. The term "radial" generally refers to the direction perpendicular to the axis "A". The terms "proximal", "rearward", "rearward", "backward" or "backward" generally refer to an axial direction in the direction "P". The terms "apical", "frontal", "forward", "depressed" or "forward" generally refer to an axial direction in direction "D". The term "glass" as used herein includes pharmaceuticals that typically require glass, including, but not limited to, some non-reactive polymers such as cyclic olefin copolymers (COCs), cyclic olefin polymers (COPs), and the like. It should be understood to include other similarly non-reactive materials suitable for use in grade applications. The term "plastic" can include both thermoplastic and thermosetting polymers. The thermoplastic polymer can be re-softened by heating to return to its original state, and the thermosetting polymer cannot be returned to its original state. The term "plastic" as used herein primarily refers to moldable thermoplastic polymers such as, for example, polyethylene and polypropylene, or acrylics, which typically include hardeners, fillers, reinforcing agents, pigments. It also contains other ingredients such as agents and/or plasticizers and can be formed or shaped by heating and pressing. As used herein, the term "plastic" is in direct contact with a therapeutic fluid that may react with the plastic or otherwise be degraded by substituents that may enter the plastic. It is not intended to include glass, non-reactive polymers or elastomers that are approved for use in certain applications. The term "elastomer," "elastomer," or "elastomer material" is primarily more deformable than plastic, but is approved for use with pharmaceutical grade fluids and is Refers to crosslinked thermoset rubbery polymers that are not easily affected by leaching or gas transfer. "Fluid" refers primarily to liquids, but suspensions in which solids are dispersed in a liquid, and either dissolved in the liquid or otherwise present within the liquid within the fluid-containing portion of the syringe. A gas can also be included. According to various aspects and embodiments described herein, reference is made to a "biasing member," such as with respect to one or more biasing members for retracting a needle or needle assembly. It will be appreciated that the biasing member can be any member capable of storing and releasing energy. Non-limiting examples include springs such as coil springs, compression or tension springs, torsion springs and leaf springs, elastically compressible or elastic bands, or any other member having a similar function. Can be mentioned. In at least one embodiment of the invention, the biasing member is a spring, preferably a compression spring.

The novel device of the present invention provides a dose control mechanism that enables accurate dosing and delivery of drug therapeutics and a drug delivery syringe that incorporates such a control mechanism. Such devices are safe and easy to use, and are aesthetically and ergonomically attractive to clinicians. The devices described herein incorporate features that make it easy for an untrained user to activate, operate and lock out the device. The novel device of the present invention provides these desirable features without any of the problems associated with known prior art devices. Some non-limiting embodiments of the novel dose control mechanism, drug delivery syringes and their components will now be further described with reference to the accompanying figures.

Various studies have shown that the accuracy of drug delivery using conventional syringes is affected by multiple factors, including the inability to accurately read and control the travel of the plunger during administration. A drug delivery syringe with a high ratio of dosing volume to axial translation (i.e., a stepwise small distance plunger push, as can be the case with large diameter syringes, delivers a significant amount of drug. This inaccuracy is greatly magnified. With the growth of high cost, low volume drug therapies entering the market, it is becoming increasingly important to accurately administer and deliver these low volume therapeutics to patients. Embodiments of the present invention overcome the challenges faced by the use of conventional syringes for the administration and delivery of low volume therapeutic agents by utilizing a novel dose control mechanism. As described further herein, the novel dose control mechanism allows the user to accurately read and administer the desired volume of drug therapeutic delivered to the patient. These devices allow the user to have a normal range of thumb travel, as they might expect with a conventional syringe, but to allow that range of thumb travel to move the plunger seal. Convert to a very limited (eg, smaller or stepped) range of. This relationship allows the user to utilize the syringe with the significant benefit of gradual low volume dose control without additional training.

FIG. 1(a) illustrates an embodiment of a novel dose control mechanism for a syringe according to at least one embodiment of the present invention. The control mechanism 10 includes a plunger 14, a housing 20, an adapter 18 and a screw 30. The plunger 14 can include the button 12 as an integrated component or a separate component. For example, the button 12 may be preformed on the proximal end of the plunger 14. Alternatively, button 12 can be a separate component attached to the proximal end of plunger 14 by a snap fit. In the preferred embodiment, the button 12 can be attached to the plunger 14, but is free to rotate axially from the plunger 14, but fixed against rotation to the user/clinician's finger. be able to. Regardless of the particular configuration and relationship of the button 12 and the plunger 14, the button 12 may have a user interface surface 12A for the user to contact and control (eg, with the user's thumb or finger tips, etc.). Is intended for.

The housing 20 has a substantially cylindrical axial through hole in which the substantially cylindrical plunger 14 can reside, at least partially. The distal end of the housing 20 is connected to and/or partially resides in the proximal portion of the adapter 18. The proximal and distal portions of the adapter 18 can be separated by an adapter flange 18A, which in turn can serve as a finger flange for use by a user. The internal aspects of these components will be described in more detail herein with reference to FIGS. 1(b), 2(a), 2(b) and 3(b). The screw 32 may reside at least partially within the housing 20 and the plunger 14 and extends distally beyond the flange 18. The screw 30 can have a threaded connection 30A aspect, and optionally a ring 32, which facilitates integrating the control mechanism with the drug delivery syringe and centers the plunger rod.

For example, the plunger rod may be removed to close the interior of the housing 20 from the environment and/or to axially align the plunger 14 within the housing 20 and by acting as a mechanical stop. To prevent, the housing 20 can optionally include a housing cover 16 at its proximal end. The housing 20 can further include a window 20A, which can be an opening (eg, an aperture) in the housing or a light transmissive or translucent component. Regardless of the particular configuration of the window 20A, its main purpose is to allow the user to identify the position of the plunger 14 within the housing 20. Plunger 14 may include one or more dose marks 14A on the outer surface of plunger 14. The housing 20 can have one or more reference marks or guide marks 20B to align the plunger dose mark 14A, such as in the window 20A. The plunger dose mark 14A can correspond to the relevant dose desired by the user. Employing each plunger mark and housing mark allows the user to control the dose volume desired to be delivered to the patient, as further described herein. In another embodiment, the window 20A can be covered by a lens, such as a transparent lens, that provides visual magnification.

2(a) and 2(b) show cross-sectional views of the dose control mechanism in the ready-to-inject and end-dose stages, respectively, according to at least one embodiment of the present invention. The cross-sectional view shows some other aspects of the components internal to this mechanism. As shown, the plunger 14 has an internal annular space 14C in which the screw 30 is at least partially present. Plunger 14 has a coarse male thread 14B (visible in FIG. 3(a)) on its outer surface that engages a coarse guide 20C along the inner surface of housing 20, and in at least one embodiment, guide 20C. Is the same as the pitch of the plunger threads 14B. Similarly, the screw 30 has a fine thread 30B that mates with the fine nut 18B of the adapter 18, and in at least one embodiment the pitch of the thread 30B of the screw is the same as the pitch of the nut 18B. 2A and 2B, the base end portion 30C of the screw 30 and the shelf portion 18C of the adapter 18 are also visible. The plunger 14 with the coarse line 14B is rotatable on the corresponding (eg, "female") coarse line guide 20C, and the plunger 14 is rotationally tightened to the screw 30 with the fine thread 30B. The terms "male" and "female" are intended to refer to corresponding mating threads or surfaces and may be used interchangeably to describe corresponding aspects, as is readily understood in the art. it can. The screw 30 with the fine screw 30B engages with the female fine nut 18B of the adapter 18. Therefore, the rotation of the plunger 14 causes the screw 30 to translate in the axial direction, and the resolution of the axial movement is determined by the pitch 30B.

The plunger 14 and the screw 30 are rotationally tightened and each has its own thread pitch so that rotational translation of the plunger 14 causes the screw 30 to rotate and translate axially. The term "tightened" is used herein to mean any number of internal aspects that releasably or (axially) slidably connect two or more components. For example, the plunger 14 can be a hollow cylinder having coarse threads on at least some portion of the outer surface and a keyway design along at least a portion of the inner surface. The keyway design is configured to mate with, transform, or relay rotation to, a complementary keyway included in the proximal end of screw 30. This keyway design element ensures that the plunger 14 and screw 30 are rotationally tightened. The keyway or rotational fastening mode is visible in the proximal end 30C of the screw 30 in FIG. 3(a), and in FIG. Any number of corresponding shapes can be utilized to provide a rotating "tightened" relationship between these components, where the first component enables a rotational tightening relationship and A second component may be removably or slidably engaged to allow axial sliding. Such components may alternatively be tightened to have, for example, a cross or plus, horizon or minus, star, or semi-circular shape, with the corresponding components being opposite to the shape of the inner annular space. Has the shape of. FIG. 1(b) shows a cross-sectional view in the plane "B" perpendicular to the axis "A" of the dose control mechanism of FIG. 1(a). As shown in FIG. 1( b ), in at least one embodiment, the screw 30 has a cross or plus shape in its vertical cross section that is fastened to the plunger 14. This arrangement or configuration allows the two components to be axially slid over each other while at the same time being rotationally tightened. Both the screw 30 and the plunger 14 reside within the housing 20 at least partially and/or at some point during operation.

A fine nut 18B (or simply "nut") having the same fines as the screw 30 may be used to secure the screw 30 and facilitate transfer of rotational movement of the plunger 14 to axial translation of the screw 30. .. The coarse to fine pitch ratio determines the degree or resolution of axial movement of the screw 30, ie, the distance the screw 30 translates axially for each revolution of the plunger 14. As a result, the physician can easily operate, which allows the physician to accurately read and set the dosage. The pitch ratio can be set to allow for "fine tuning" of the dosage, which is especially important for low volume dosages where the movement of the plunger can significantly affect the variation. is there.

During operation of the dose control mechanism, the user can rotate the plunger 14 axially or depress the button 12 to control the desired dosage for injection into the patient's body. As shown in FIGS. 3(a) and 3(b), axial rotation of the plunger 14 causes the coarse threads 14B (seen in FIG. 3(b)) to move within the corresponding coarse guides 20C of the housing 20. Moving. This action causes the plunger 14 to translate axially in the distal direction, thereby reducing the dosage within the drug chamber, as described in more detail herein. Due to the rotation-tightening interaction between the plunger 14 and the screw 30 in the annular space 14C, rotation of the plunger 14 causes the screw 30 to rotate and translate axially. However, because of the pitch ratio between the plunger 14 and the screw 30, each unit measure of translation in the distal direction of the plunger 14 causes a slight (eg, smaller, more resolved) translation of the screw 30 in the distal direction. Is brought about. This has many benefits for precise control during delivery of low volume doses. Primarily, the pitch ratio relationship allows the user to precisely control the desired dosage and delivery of the drug therapeutic. In addition, this pitch ratio relationship allows the user to operate the syringe in a conventional manner, such as by depressing the plunger 14 a significant distance while providing only a slight or small translation of the screw.

The novel dose control mechanism of the present invention also utilizes a feature that provides an integrated adjustable range of travel limits to ensure accurate delivery of low dose drug therapeutics. This may be possible, for example, by incorporating features that prevent variable depressing of the plunger seal (or stopper) within the syringe (eg, preventing the plunger from "bottoming out" during drug delivery). it can. Specifically, the dose control mechanism of the present invention utilizes an adjustable set mechanical end point for the range of axial movement of the plunger during drug delivery. Such limits may be pre-specified by the physician prior to use, i.e., incorporated and secured in the syringe configuration, or adjustable, i.e., by the compounding pharmacist, physician, or integral medication Self-administered patients using the setting mechanism can be variably controlled. Such mechanical set points allow, for example, a range of axial plunger movements related to priming and dose, but also allow the user to variably depress the plunger and plunger seal as part of the dosing stroke. To prevent bottoming out of these components within the dosing chamber of the syringe. This novel control mechanism greatly improves the accuracy of the dose delivered to the patient. Further, embodiments of the present invention allow the user to prime the syringe to evacuate residual air from the dosing chamber prior to delivering the dose to the patient. The priming step can be a fixed or variable amount, depending on the configuration of the low dose syringe and variations in the amount of drug or liquid contained/filled in the dosing chamber. The novel syringe configuration allows the user to complete the priming step while maintaining or enabling the syringe to deliver accurate and precise doses to the patient.

As mentioned above, mechanical set point limits prevent the user from variably depressing the plunger and plunger seal, or preventing these components from bottoming out within the dosing chamber of the syringe. It works effectively to prevent you from doing so. This feature improves the accuracy of the dose delivered to the patient by reducing variability in the delivered dose from the amount prescribed and intended to be delivered to the patient. The mechanical end point can be easily confirmed and easily set by adopting the pitch ratio between the plunger 14 having the coarse screw 14B and the screw 30 having the fine screw 30B. For example, in one such embodiment, the pitch ratio between the coarse and fine can be 4:1 so that the plunger 14 can be rotated to "screw" or rotate. The element translates axially four times more than the axial translation of the screw component. Therefore, the doctor can set the required dosage more accurately, which significantly facilitates the operation. Such a pitch ratio can be anything in the range, for example, 1:1 to 20:1, as may be needed to obtain the required accuracy of low volume dosage. "Dialing" or "setting" can be facilitated by the dose marks on the plunger and guide marks on the housing described above.

When the user depresses button 12, which causes the plunger 14 to rotate and set the desired low volume dosage for injection, the user is known in the art as the "priming step". It can be performed. This priming step empties any residual air bubbles, if any, trapped in the dosing chamber during pre-filling from the dosing chamber prior to delivery and primes the attached needle (or catheter or expansion set). After priming by pressing the button 12 and setting the dose are complete, the button 12 can be further depressed to reach the bottom, thereby injecting the desired dose into the patient. Upon delivery of the drug dose, the plunger 14 "bottoms" over the ledge 18C of the adapter 18 (as shown in FIG. 2(b)). Due to the pitch ratio between the plunger 14 and the screw 30, the plunger 14 is depressed or axially in the distal direction (ie, in the direction of the solid arrow in FIGS. 2(a) and 2(b)). When translating, the screw 30 translates axially in the distal direction by a small fraction of the distance translated by the plunger 14. This difference in axial translation distance between the plunger 14 and the screw 30 is apparent by comparing the distances D1 and D2 in FIGS. 2(a) and 2(b). D1 is the distance that the plunger 14 translates in the axial direction, and D2 is the stepwise distance that the screw 30 translates in the axial direction. The difference between the dimensions D1 and D2 is also apparent from the reduction of the annular space 14C of the plunger 14 when checking the relative position of the proximal end 30C of the screw 30 (Fig. 2(a) and Fig. 2( Compare b)). Therefore, the variable annular space 14C of the plunger 14 is associated with the mechanical set point desired by the physician and provides space for translation of the screw 30 during the dosing stroke.

In particular, the novel embodiments contemplated by the present invention effectively prevent the plunger seal from "bottoming" within the dosing chamber. This prevents one aspect of user variability in either overdosing due to excessive depression of the plunger or underdosing due to insufficient depression of the plunger, and the amount administered to the patient is accurate and Make sure to minimize the negligence. This is especially important in low-dose therapy where user-related negligence can lead to significant and undesirable variability and inaccuracy in the delivery of pharmaceuticals to patients. Embodiments in accordance with the present invention act to prevent this from occurring and to effectively eliminate the negligence of administration associated with conventional syringe configurations and delivery methods. Furthermore, the screw is not reversely driven by pressing the plunger in this embodiment.

The novel dose control mechanism of the present invention can be incorporated into many drug delivery syringe configurations to provide the user with accurate dose delivery capabilities. For example, the control mechanism can be utilized with a fill-in-use syringe, a drug-filled syringe, or a safety syringe with integrated needle storage or needle-covering safety features, or a combination thereof. Further, the dose control mechanism according to the teachings of the present disclosure can be utilized with so-called mixed syringes, as well as conventional syringes. For example, the dose control mechanism can be incorporated into a syringe such as that disclosed in US patent application Ser. No. 13/566,079, which application is referenced to all disclosed therein. Incorporated herein by reference.

Below is provided an example of such a syringe incorporating a novel dose control mechanism. By employing a respective plunger 14 and, optionally, a dose mark 14A and a guide mark 20B, the user is able to control the volumetric dose desired to be delivered to the patient in the syringe. You can The plunger dose mark 14A can correspond to the relevant dose desired by the user. The user first utilizes the plunger to align the desired dose mark 14A with the guide mark 20B, such as by axially depressing a button or rotating the plunger, to obtain the desired dose. You can confirm and select. The axial rotation of the plunger 14 causes the plunger 14 to translate axially in the distal direction, and this movement is transmitted to the screw 30 by the mechanism described above. Axial translation of the screw 30 in the distal direction causes the drug fluid contained within the drug chamber of the syringe to be dispensed through the needle of the barrel adapter assembly. Once the desired dose has been identified and selected by the user, the remaining amount of drug fluid in the drug chamber is substantially the exact amount desired to be injected. The syringe can then be inserted into the patient's body for drug delivery. After insertion of the needle into the patient's body, the user can further push plunger 14 (and/or button 12) axially in the distal direction to deliver the drug dose. Due to the novel aspect of the invention, including the pitch ratio and mechanical stop mechanism described above, the dose accuracy is finely controlled and variability is reduced. In an embodiment of the invention intended for a fill-in-use syringe, the plunger 14 and screw 30 initially function in the opposite manner (eg, axially translated in the proximal direction) to exit the vial or container. Withdraw the drug fluid and fill the drug chamber of the syringe. In embodiments of the invention intended for retractable or safety syringes, the plunger 14 and screw 30 are adapted to activate or activate the needle retractor or safety mechanism after a substantial drug dose has been delivered. Can function. These embodiments of the invention will be discussed in more detail below with reference to the accompanying figures.

FIG. 4(a) illustrates an embodiment of the dose control mechanism 10 as a component of an exemplary fill-in-use drug delivery syringe 100, a syringe that a user can fill with a withdrawal medication. As shown, the control mechanism 10 includes a plunger 14, a housing 20, an adapter 18 and a screw 30. The plunger 14 can include the button 12 as an integrated component or a separate component, as described above. The housing 20 optionally has a housing cover at its proximal end, for example, to close the interior of the housing 20 from the environment and/or to axially align the plunger 14 within the housing 20. 16 may be included. The housing 20 can further include a window 20A, which can be an opening (eg, an aperture) in the housing or a light transmissive, translucent and/or optionally a magnifying component. Plunger 14 may include one or more dose marks 14A on the outer surface of plunger 14. The housing 20 can have one or more reference or guide marks 20B to align the plunger dose mark 14A, such as in the window 20A. The control mechanism 10 may be attached, mounted, affixed, or otherwise connected to the proximal end of the barrel 140 such that at least a portion of the screw 30 resides inside the barrel 140.

FIG. 4( b) shows an enlarged isometric view of the tip of the drug delivery syringe shown in FIG. 4( a ). The screw 30 may be directly or indirectly connected to the plunger seal 136 to drive the axial translation of the plunger seal 136. In the indirect connection configuration, a plunger rod 134 may be utilized to connect the components between the screw 30 and the plunger seal 136. The plunger rod 134 can be connected to the screw 30 in a threaded connection 30A version, for example. Optionally, a ring 32 near the tip of screw 30 may be utilized to facilitate connection of screw 30, plunger rod 134 and plunger seal 136. The threaded connection 30A aspect and ring are visible in Figures 2(a), 2(b) and 3(b). In at least one embodiment, the threaded connection 30A aspect is connected to the plunger rod 134 through the plunger rod radial opening. Additionally or alternatively, the connection may be a snap fit connection, an interference fit connection, or many other connection methods known in the art. In at least one other embodiment, the threaded connection aspect is connected to the plunger rod through the proximal opening of the plunger rod such that it is located within the proximal pocket of the plunger rod. Preferably, the connection between the screw 30 and the plunger seal 136, or if the plunger rod is employed, between the screw 30 and the plunger rod 134, secures the plunger rod and/or the plunger seal against rotation. The screw is allowed to rotate axially while remaining retained. Therefore, when the plunger 14 and the screw 30 of the control mechanism 10 rotate and translate in the axial direction, the movement is relayed to the plunger seal 136, and the plunger seal 136 also translates in the axial direction.

When utilized in a point-of-use syringe, the plunger 14 and screw 30 initially function in reverse (eg, axially translated in the proximal direction) to draw drug fluid from the vial or container, Fill 100 drug chambers 138. As described above, the user can then utilize the control mechanism 10 to identify and select the drug dose to be delivered. The user can then insert the needle into the patient's body for drug delivery. The user can then depress the button 12 and/or the plunger 14 to translate the plunger 14 and screw 30 axially. Due to the function of the control mechanism and the pitch ratio, any measure of the distal translation of the plunger 14 results in only a gradual measure of the distal translation of the screw 30, allowing precise dose delivery control by the user. Axial translation of screw 30 results in axial translation of plunger seal 136. This axial movement of the plunger seal 136 distally forces the drug fluid out of the drug chamber 138 of the barrel 140 through the needle 154 of the barrel adapter assembly 150 for injection and delivery to the patient.

Similarly, the novel control mechanism of the present invention may be utilized with drug-filled syringes, that is, syringes that are filled with a drug therapeutic by the manufacturer and ready for injection by the user. FIG. 5( a) illustrates an embodiment of the dose control mechanism 10 as a component of an exemplary drug-filled drug delivery syringe 200. As shown, the control mechanism 10 includes a plunger 14, a housing 20, an adapter 18 and a screw 30. The plunger 14 can include the button 12 as an integrated component or a separate component, as described above. The housing 20 is optionally at its proximal end, for example, for axially aligning the plunger 14 within the housing 20, to close the interior of the housing 20 from the environment, and/or. A housing cover 16 may be included to prevent accidental removal by the user/clinician. The housing 20 can further include a window 20A, which can be an opening (eg, an aperture) in the housing, or a light transmissive or translucent component. Plunger 14 may include one or more dose marks 14A on the outer surface of plunger 14. The housing 20 may have one or more reference or guide marks 20B with which the plunger dose marks 14A should be aligned or identified, such as in the window 20A. The control mechanism 10 may be attached, mounted, affixed, or otherwise connected to the proximal end of the barrel 140 such that at least a portion of the screw 30 resides inside the barrel 140.

FIG. 5( b) shows an enlarged isometric view of the tip of the drug delivery syringe shown in FIG. 5( a ). The screw 30 may be connected directly or indirectly to the plunger seal 236 to drive the axial translation of the plunger seal 236. In the indirect connection configuration, the plunger rod 234 can be utilized to connect the components between the screw 30 and the plunger seal 236. Plunger rod 234 can be connected to screw 30, for example, in a threaded connection 30A version. In at least one embodiment, the threaded connection aspect is connected to the plunger rod through the proximal opening of the plunger rod such that it is located in the proximal pocket of the plunger rod. Additionally or alternatively, the connection may be a snap fit connection, an interference fit connection, or many other connection methods known in the art. In at least one embodiment, as described further below with reference to Figures 7A(a)-7B(d), the screw, threaded connection aspect and plunger rod include a drug chamber filled with a drug fluid and a plunger seal. And the plunger rod is configured to be easily connectable after being inserted into the proximal end of the barrel. Preferably, the connection between the screw 30 and the plunger seal 236, or the screw 30 and the plunger rod 234 if a plunger rod is employed, secures the plunger rod and/or the plunger seal against rotation. The screw is allowed to rotate axially while remaining retained. Therefore, when the plunger 14 and the screw 30 of the control mechanism 10 rotate and translate in the axial direction, the movement thereof is relayed to the plunger seal 236, and the plunger seal 236 also translates in the axial direction. When utilized with a drug-filled syringe, the control mechanism 10 is generally attached to the barrel 240 after the drug chamber 238 of the barrel 240 is filled with drug fluid. This is often desired so that the syringe 200 can be filled and assembled in a standard pharmaceutical fill and finish process line. Once the syringe 200 is filled and assembled, the control mechanism 10 can be utilized by the user to confirm and set the selected drug dose for delivery. The user can then insert the needle into the patient's body for drug delivery. The user can then depress the button 12 and/or the plunger 14 to translate the plunger 14 and screw 30 axially. Due to the function of the control mechanism and the pitch ratio, any measure of distal translation of the plunger 14 will only result in a stepwise measure of distal translation of the screw 30, allowing precise dose delivery control by the user. .. Axial translation of screw 30 results in axial translation of plunger seal 236. This axial movement of the plunger seal 236 in the distal direction pushes the drug fluid out of the drug chamber 238 of the barrel 240 through the needle 254 of the barrel adapter assembly 250 for injection and delivery to the patient.

Further, the novel control mechanism of the present invention can be utilized in safety syringes, such as retractable needle safety syringes (ie, syringes incorporating needle safety features). FIG. 6( a) illustrates an embodiment of the dose control mechanism 10 as a component of the exemplary retractable drug delivery syringe 300. As shown, the control mechanism 10 includes a plunger 14, a housing 20, an adapter 18 and a screw 30. The plunger 14 can include the button 12 as an integrated component or a separate component, as described above. The housing 20 is optionally at its proximal end, for example, for axially aligning the plunger 14 within the housing 20, to close the interior of the housing 20 from the environment, and/or. A housing cover 16 may be included to prevent accidental removal of the. The housing 20 can further include a window 20A, which can be an opening (eg, an aperture) in the housing or a component that provides light transmission, translucency, and/or optical magnification. Plunger 14 may include one or more dose marks 14A on the outer surface of plunger 14. The housing 20 can have one or more reference marks or guide marks 20B with which the plunger dose mark 14A should be aligned or otherwise identified, such as in the window 20A. The control mechanism 10 may be attached, mounted, affixed, or otherwise connected to the proximal end of the barrel 140 such that at least a portion of the screw 30 resides inside the barrel 140.

FIG. 6(b) shows an enlarged isometric view of the tip of the drug delivery syringe shown in FIG. 6(a). The screw 30 may be directly or indirectly connected to the plunger seal 336 to drive the axial translation of the plunger seal 336. In the indirect connection configuration, a plunger rod 334 can be utilized to connect the components between the screw 30 and the plunger seal 336. Plunger rod 334 can be connected to screw 30, for example, in a threaded connection 30A version. Screw connection aspects are known in the configurations described above with reference to Figures 4(a) and 4(b), in the configurations described above with reference to Figures 5(a) and 5(b), or known in the industry. Can be connected to the plunger rod in any number of other ways. Preferably, the connection between the screw 30 and the plunger seal 336 or, if a plunger rod is employed, between the screw 30 and the plunger rod 334 secures the plunger rod and/or the plunger seal against rotation. The screw is allowed to rotate axially while remaining retained. Therefore, when the plunger 14 and the screw 30 of the control mechanism 10 rotate and translate in the axial direction, the movement thereof is relayed to the plunger seal 336, and the plunger seal 336 also translates in the axial direction. Plunger 14 and screw 30 can function to activate or activate the needle storage or safety mechanism after a substantial drug dose has been delivered.

When utilized in a safety syringe, such as a retractable needle safety syringe, the plunger 14 of the control mechanism 10 can activate or activate the needle safety mechanism. Suitably, the needle safety mechanism is a biasing member such as a spring, elastic or other member capable of storing and releasing energy facilitating needle storage, a needle coating, or an accidental needle stick to the user. Facilitated, such as by any other method of protection from wounds. The safety syringe can include any needle safety mechanism, such as a needle retracting safety mechanism or a needle covering safety mechanism, operable with the control mechanism and syringe disclosed herein. By way of example, the needle safety mechanism may include, but is not limited to, WO 2006/119570, WO 2006/108243, WO 2009/003234, WO 2011/075760, and/or It may be a needle retracting safety mechanism such as that described in US Pat. No. 8,702,653. In at least one embodiment of the present invention, the syringe 300 is a needle storage safety syringe and incorporates a needle storage safety mechanism 356 as disclosed in US Pat. No. 8,702,653.

Such needle storage safety mechanism 356 can be assembled to syringe barrel 340 through the tip of barrel 340, for example, as part of barrel adapter assembly 350. The control mechanism 10 is generally attached to the barrel 340 after the drug chamber 338 of the barrel 340 has been filled with drug fluid. This is often desirable so that the syringe 300 can be filled and assembled in a standard pharmaceutical fill and finish process line. Once the syringe 300 is filled and assembled, the control mechanism 10 can be utilized by the user to identify and set the drug dose for delivery. The user can then insert the needle into the patient's body for drug delivery. The user can then depress the button 12 and/or the plunger 14 to translate the plunger 14 and screw 30 axially. Due to the function of the control mechanism and the pitch ratio, any measure of distal translation of the plunger 14 will only result in a stepwise measure of distal translation of the screw 30, allowing precise dose delivery control by the user. .. Axial translation of screw 30 results in axial translation of plunger seal 336. This axial movement of the plunger seal 336 in the distal direction forces the drug fluid out of the drug chamber 338 of the barrel 340 through the needle 354 of the barrel adapter assembly 350 for injection and delivery to the patient. At the end of drug delivery, the plunger seal 336 contacts the components of the needle storage safety mechanism 356 to activate the storage mechanism, resulting in the storage of the needle 354 within the barrel 340 of the syringe 300. The screw 30 and other components or control mechanism 10 can be configured or adjusted to allow this additional range of axial translation in the distal direction after the desired drug dose has been delivered. Then, as the needle 354 is retracted into the barrel 340 of the syringe 300, the components of the needle storage safety mechanism 356 abut and push the plunger seal 356 in the proximal direction. As the retracting force continues, the user can controllably reduce the force he exerts on the button 12 and/or the plunger 14 as the screw 30 and the plunger 14 move proximally, thereby speeding the needle retracting. Can be controlled. Accordingly, the needle retractor safety mechanism 356 provides many additional desirable features to the novel syringe of the present invention.

As will be readily appreciated by those skilled in the art, the barrel adapter assembly can be attached, mounted, glued, or otherwise connected to the tip of the barrel by many known methods. For example, a luer connection can be utilized to connect the barrel adapter assembly to the syringe barrel. The luer connection system is a standard way of attaching syringes, catheters, hubbed needles, IV tubing, etc. to each other. The luer connection consists of conical/tubular female and male interlock components that are slightly tapered to better hold one another. The luer connection may be a “luer slip” as shown in FIGS. 4(a) and 4(b), which is a luer connection with a simple pressure or torsion fit, or the luer connection may be more reliable. It can be a "luer lock" as shown in Figures 5(a) and 5(b), which can have an additional outer rim threaded to be tightened. Alternatively, the connection can be facilitated by a barrel adapter connection. By way of example, the barrel adapter connection can be as described in, but not limited to, WO 2011/137488 and/or US Pat. No. 8,702,653. A luer connection, an interference fit connection, a barrel adapter connection, or any number of other known connections may be utilized to attach the barrel adapter assembly to the barrel while still within the breadth and scope of the present invention. Regardless of the type of barrel adapter assembly utilized, the barrel adapter assembly generally comprises barrel tips 152, 252, 352 and needles 154, 254, 354, respectively. In some configurations, barrel tips 152, 252, 352 may be preformed features at the barrel tips. Alternatively, barrel tips 152, 252, 352 may be separate components attached to the barrel tips. Needles 154, 254, 354 can be any type of fluid conduit, including, for example, flexible cannulas or rigid needles, and can be made from any number of materials, including stainless steel. The types of connections described herein can be utilized regardless of the type of syringe with which they are shown. For clarity, the luer slip connection shown in the in-use fill syringe in FIGS. 4(a) and 4(b) may be utilized in the drug-filled syringe in FIGS. 5(a) and 5(b). Or, any other type of connection can be used with any other type of syringe described herein.

From the foregoing, it is understood that the novel dose control mechanism and syringe disclosed herein provide an efficient and easily operated system for accurate dose setting and delivery of drug therapeutics. Will be done. Such devices are safe and easy to use and are aesthetically and ergonomically attractive to clinicians. Embodiments of the present invention overcome the challenges faced with the use of conventional syringes for the administration and delivery of low volume therapeutic agents by utilizing a novel dose control mechanism. The novel dose control mechanism allows the user to accurately read and administer the desired volume of drug therapeutic delivered to the patient. These devices allow the user to have a normal range of thumb travel, as they would normally expect from a conventional syringe, but to achieve that range of thumb travel of the plunger seal. Convert to a very limited (eg, smaller or graduated) range of movement. This relationship allows the user to utilize the syringe with the significant benefit of gradual low volume dose control without additional training.

Assembling and/or manufacturing the control mechanism 10, the syringe 100, the syringe 200 or the syringe 300, or any of the individual components can utilize many materials and methods known in the art. For example, many known cleaning fluids such as isopropyl alcohol and hexane can be used to clean components and/or devices. Many known adhesives or glues can be employed as well in the manufacturing process. For example, a glue or an adhesive may be used to connect the distal end of the housing 20 to the proximal end of the adapter 18. Similarly, glue or adhesive may be utilized to connect the tip of the adapter 18 to the proximal end of the barrel. In addition, known siliconizing fluids and processes can be employed during the manufacture of new components and devices. Furthermore, known sterilization processes can be employed during one or more of the manufacturing or assembly stages to ensure the sterility of the final product.

In one embodiment, the method of assembling the control mechanism includes: (i) threading a fine thread at least partially through a fine nut of the adapter; and (ii) passing a plunger, wherein the plunger is coarse on its outer surface. A step of: (iii) having an internal thread through an internal axial through hole of the housing, the internal surface of the housing having a corresponding coarse guide, and (iii) an annular space of the plunger. Inserting at least the proximal portion of the screw through the distal portion of the plunger, and (iv) attaching the outer distal portion of the housing to the proximal aspect of the adapter.

In addition, the plunger can include a button at its proximal end. The button can be a preformed aspect of the plunger or it can be a separate component from the plunger. Preferably, the button is a separate component attached to the plunger, for example by a snap fit. Similarly, the housing can include a housing cover at its proximal end. The housing cover can be a preformed version of the housing or it can be a separate component from the housing. As mentioned above, glue or adhesive may be utilized to attach one or more components of the control mechanism to each other. Alternatively, one or more components of the control mechanism may be an integrated component. For example, the housing can be a separate component that is affixed to the adapter by glue, or the adapter can be a preformed feature at the tip of the housing that is glued to the barrel. Similarly, the housing cover can be attached to the housing with glue. These components can be sterilized individually or together and can be assembled in a sterile environment or sterilized after assembly. The barrel can be siliconized before or after assembly.

The control mechanism can be utilized as a component of the syringe. In one embodiment, a method of manufacturing a syringe with a control mechanism includes: (i) attaching a barrel adapter assembly to the distal end of a syringe barrel; (ii) attaching a plunger seal through the proximal end of the syringe barrel; (Iii) attaching a control mechanism to the proximal end of the syringe barrel, wherein the control mechanism may remain in contact with the plunger seal.

The method of manufacturing a syringe may further include the step of (ii) at least partially filling the barrel with a fluid substance prior to the step of attaching the plunger seal through the proximal end of the syringe barrel. Step (iii) may further require connecting the threaded connection aspect of the thread of the control mechanism directly to the plunger or indirectly through a plunger rod connected to the proximal end of the plunger seal. The connection between the plunger rod and the plunger seal can be any number of connections including, but not limited to, threaded connections, snap fit connections, interference fit connections, capture connections, and the like. In at least one embodiment, the threaded connection aspect is connected to the plunger rod through a radial or proximal opening in the plunger rod such that it is located in the proximal pocket of the plunger rod. Additionally or alternatively, the connection may be a snap fit connection, an interference fit connection, or many other connection methods known in the art. Preferably, the connection between the screw and the plunger seal or, if a plunger rod is employed, between the screw and the plunger rod, keeps the plunger rod and/or the plunger seal fixed against rotation. , The screw can rotate in the axial direction.

One preferred method of making a syringe with a dose control mechanism, according to one embodiment of the present invention, will now be described with reference to Figures 7A(a)-7B(d). FIG. 7A(a) shows a drug-filled syringe such as that described with reference to FIGS. 5(a) and 5(b) above, wherein the adapter is a proximal adapter portion 418P and a distal end. 2 is a two component adapter having an adapter portion 418D. The proximal adapter portion 418P has one or more connecting protrusions 418E and the distal adapter portion 418D has corresponding connecting holes 418F. When pressed together, the connection protrusions 418E and corresponding connection holes 418F mate, mate, or otherwise join to integrate the two parts of the adapters 418P, 418D. First, the cap 460 can be connected to the tip of the barrel 440 of the syringe 400. A distal adapter portion 418D can be slidably mounted on the outside of the barrel. Inside the barrel 440, ie, the drug chamber 438, can be filled with drug fluid or substance through the open proximal end of the barrel. Plunger seal 436 can be mounted in the barrel through the proximal end for fluid contact. An optional plunger rod 434 can be connected to the plunger seal 436 before or after inserting the plunger seal 436 into the barrel 440. These steps can be performed in a sterile environment to maintain the integrity of the container and the sterility of the drug treatment.

The rest of the syringe can then be assembled in a non-sterile or sterile environment. The screw can be connected as a component of the control mechanism, then to the plunger seal, or to the plunger rod if a plunger rod is employed. Then, the distal end side adapter portion 418D can be slid in the proximal direction along the outside of the barrel to be connected to the proximal end adapter portion 418P as described above. The connection between the distal adapter portion 418D and the proximal adapter portion 418P allows the barrel flange 440A aspect of the barrel 440 to be captured to maintain the control mechanism 10 at the proximal end of the barrel 440. Utilizing a variety of glues or adhesives to ensure that these components and connections are held in place during assembly, filling, manufacturing, shipping, storage and operation of the novel device of the present invention. You can The final assembly of the syringe, such as in drug-filled syringe 400, may appear as shown in Figure 7A(b). Drug-filled syringes of this kind are variably selectable by the user, for example, when the syringe should be filled with a standard amount of drug fluid by a pharmaceutical company or contract drug filler. At times, the needle length is variably selectable by the user, or in many other situations. FIG. 7B(c) shows a drug-filled syringe with a selectable needle attached via a luer lock connection, as described above. In such a scenario, the syringe may be held with the tip of the syringe pointing upwards. The cap 460 (shown in FIG. 7A(b)) can be removed and replaced with the barrel adapter assembly 450. Barrel adapter assembly 450 includes a barrel tip 452 and a needle 454 that the user can select and attach to a drug-filled syringe shortly before use. As described above, the user can confirm and select the drug dose. Comparison of drug-filled syringe 400 in FIGS. 7B(c) and 7B(d) reveals differences between drug-filled syringes immediately before and after injection and delivery of a drug dose to a patient. Due to the pitch ratio between the plunger 14 and the screw 30, the plunger 14 is depressed or in the proximal direction (ie, in the direction of the solid arrow in FIGS. 7B(c) and 7B(d)). When translating, the screw 30 translates axially in the distal direction, merely stepwise or to a smaller distance. The difference in the axial translation distance between the plunger 14 and the screw 30 is apparent by comparing the distances D3 and D4 in Figures 7B(c) and 7B(d). D3 is the distance that the plunger 14 translates in the axial direction, and D4 is the short distance that the screw 30 translates in the axial direction.

8A-8C show yet another embodiment of a syringe 500 that incorporates a dose control mechanism 510. The embodiments of FIGS. 8A-8C provide utilization of both the dose control mechanism of the embodiments described above and the advantages of conventional syringes, as described below. 8A, 8B and 8C show cross-sectional views of the dose control mechanism in the injection ready stage, the partial injection stage and the end of administration stage, respectively, and FIGS. 9(a) and 9(b) show The partial assembly exploded view of the dose control mechanism 510 of this embodiment is shown.

Similar to the embodiments described above, the dose control mechanism 510 for the syringe 500 includes a plunger 514, a housing 520, an adapter 518 and a screw 530. The housing 520 has a substantially cylindrical axial through hole in which a substantially cylindrical plunger 514 can be at least partially present. The tip of the housing 520 includes an adapter 518. The housing 520 and adapter 518 of this embodiment are formed as a unitary structure, with the adapter 518 presenting a finger flange for engagement by a user during use. However, the housing 520 and the adapter 518 can be formed separately, as shown for other embodiments.

The adapter 518 may couple the dose control mechanism 510 to the barrel 540 of the syringe 500 by any suitable structure. In the illustrated embodiment, the adapter 518 is coupled to the barrel 540 by an insert 518A that is received in a laterally extending opening 518B of the adapter 518. The insert 518A shown includes a gasket 518C and a locating insert 518D, although the insert can be of any suitable design. The barrel 540 of the syringe 500 is received within the opening of the gasket 518C and the barrel flange 540A is located along the top surface of the gasket 518C. Gasket 518C and barrel 540 are inserted through the openings of positioning inserts 518D that can be slidably received within laterally extending openings 518B of adapter 518, with laterally extending flanges 518E It can serve to keep 518A and associated barrel 540 in place. Thus, during assembly, barrel 540 can be inserted into the openings of gasket 518C and locating insert 518D and then slid into place within laterally extending opening 518B of adapter 518.

Similar to the embodiments above, the screw 530 may be coupled to the plunger rod 534 directly or indirectly in any suitable manner. For example, similar to the embodiment of FIGS. 1(a)-7B(d), the connection feature 530A of the screw 530 can be received within the recess 534A at the proximal end of the plunger rod 534. In the illustrated embodiment, the tip of the plunger rod 534 is coupled to the plunger seal 536 by a threaded connection, although alternative connections known in the art can be provided. Similarly, the plunger seal 536 can be of any suitable design. For example, in the illustrated embodiment, multiple ring seals 536A are disposed within corresponding multiple peripheral recesses 536B of plunger seal 536.

For example, to close the interior of the housing 520 from the environment and/or to axially align the plunger 514 within the housing 520 and to prevent removal of the plunger rod by functioning as a mechanical stop. The housing 520 can optionally include a housing cover 516 at its proximal end.

The housing 520 can further include a dosage reference configuration. For example, as described in more detail above, the housing 520 can be provided with a window 520A (see FIG. 9(b)) that allows the user to administer one or more doses to the outer surface of the plunger 514. By confirming the position of the mark, the position of the plunger 514 inside the housing 520 can be confirmed. Although not shown in detail in this embodiment, it will be appreciated by those skilled in the art that the same or similar configurations can be provided in this embodiment as in the previous embodiments.

Plunger 514 can include a button 512, which presents a user interface surface 512A that a user engages to axially translate plunger 514 within housing 520. Button 512 and plunger 514 can be integrated components or separate components. For example, the button 512 can be a preformed feature on the proximal end of the plunger 514. Alternatively, the button 512 can be a separate component attached to the proximal end of the plunger 514 by a snap fit. In at least one embodiment, the button 512 can be attached to the plunger 514 but is free to rotate about the proximal end of the plunger 514. In this way, the button 512 can be fixed against rotation to the user/clinician's finger while allowing the plunger 514 to rotate as the plunger translates axially.

Plunger 514 can further include a plunger dial 517 that can provide alternative or additional structure for operating plunger 514. In the illustrated embodiment, for example, the plunger dial 517 is fixed to the plunger 514. As a result, by rotating the plunger dial 517, the user can directly rotate the plunger 514 upon request. Thus, depending on which direction the plunger rotates, the plunger dial 517 can be rotated to retract or administer the drug.

Similar to the embodiment of FIGS. 1(a)-7A(b), the screw 530 is at least partially disposed within the axially extending channel 514C in the plunger 514. As shown in FIG. 1( b) with respect to the screw 30 and the plunger 14, the proximal length portion 530 C of the screw 530 is axially fastened to the plunger 514 so as to slide relative to the axial direction. Thus, the axial rotation of the plunger 514 causes the screw 530 to rotate in the axial direction. Similar to the embodiments described above, those skilled in the art will appreciate that the axial tightening may be other than that specifically illustrated in FIG. 1(b).

Similar to the above-described embodiment, a male thread is formed on the distal side length portion 530B of the screw 530 so as to complementarily engage with the female thread portion 518F of the adapter 518. As a result, rotation of screw 530 results in rotation of screw 530 within adapter 518, as can result from rotation of axially tightened plunger 514. Since the axial direction in which the screw 530 translates depends on the direction of rotation of the screw 530, the translation of the associated plunger rod 534 and plunger seal 536 also depends on the direction of rotation of the screw 530.

Plunger 514 is received within longitudinally extending channel 520D within housing 520. To provide axial and rotational movement of the plunger 514 relative to and within the housing 520, the longitudinally extending channel 520D and the plunger 514 are coupled by an engagement thread configuration. To this end, one of longitudinally extending channel 520D and plunger 514 includes a length of thread and the other of longitudinally extending channel 520D and plunger 514 is a coarse thread. Including at least one thread segment positioned to engage. In the illustrated embodiment, the longitudinally extending channel 520D includes a thread 520C and the plunger 514 includes a thread segment 514B, where the thread 520C of the longitudinally extending channel 520D is a double thread. Being threaded, the plunger 514 includes a pair of thread segments 514B.

However, one of ordinary skill in the art will appreciate that in at least one embodiment, the configuration of the engaging thread pitch for plunger 514 and housing 520 can be reversed. In other words, the outer surface of the plunger 514 can include a length of coarse thread, with the longitudinally extending channel 520D being at least one arranged to engage the thread of the plunger 514. Includes thread segment. Those of ordinary skill in the art will appreciate that the thread segments along the inner surface of the longitudinally extending channel 520D may include thread recessed segments in which the male threads of the plunger 514 rotate and axially. It will be further understood that it can be mounted as it translates into. For the purposes of this disclosure, the term "thread segment" can include both thread recesses that can receive threads and threads that can be received within the thread recesses.

In accordance with aspects of the embodiment of FIGS. 8A-9(b), engagement of the plunger 514 and housing 520 provides uniform alignment as shown for the embodiment of FIGS. 1(a)-3(b). It is provided by the variable pitch thread 520C rather than the eye thread. In this way, the rotation of the plunger 514 relative to the axial rotation of the plunger 514 within the housing 520, and consequently the rotation and axial translation of the screw 530 relative to the housing 520, can be more closely matched. Moreover, this configuration allows the user to fill the syringe more easily and quickly.

For the purposes of this disclosure, the term “variable pitch thread” 520C means that the thread includes at least two thread pitches for thread segment 514B to engage (FIG. 9(b)). reference). The first thread pitch 520E is arranged toward the front end portion of the housing 520, and the second thread pitch 520F is arranged in the housing 520 on the proximal side toward the first thread pitch 520E.

In this embodiment, the first thread pitch 520E is a coarse thread as shown with respect to the embodiment of FIGS. 1(a)-3(b), and the second thread pitch 520F is the first thread. The pitch is relatively finer than the mountain pitch 520E. As a result, when the plunger 514 rotates and the thread segment 514B engages with the first pitch thread 520E, the plunger 514 is released as described above with respect to the embodiment of FIGS. 1(a)-3(b). Move in the axial direction. In other words, if the user advances the plunger 520 with the thread segment 514B engaged with the first thread pitch 520E, the plunger 520 will move a greater distance than the tightened, relatively small pitch thread 530. , Move in the axial direction. Conversely, if the user advances the plunger 520 with the thread segment 514B engaged with the second thread pitch 520F, the thread pitch of the plunger 520 and the screw 530 will be more closely aligned. It As a result, the axial distance traveled by plunger 520 and screw 530 will more closely match. Thus, when the user moves the plunger 520 proximally at a relatively constant rate to draw the medication into the barrel 540, the thread segment 514B is positioned at the first thread pitch 520E. Thus, the drug is initially drawn slowly into the barrel 540 and more quickly when the thread segment 514B is placed in the second thread pitch 520F. Thus, the variable pitch thread 520C facilitates more rapid withdrawal of a larger volume of drug than the embodiment of FIGS. 1(a)-3(b). Similarly, when the plunger 520 is depressed to prime the syringe or administer the medication, the rate at which the plunger seal 536 moves within the barrel 40 depends on the position of the thread segment 514B within the variable pitch thread 520C. Determined, allowing for faster priming initially and slower final delivery of drug. In at least one embodiment, upon completion of the priming step of operation, the thread segment 514B is positioned at the first thread pitch 520E of the variable pitch thread 520C. This allows the drug to be accurately delivered to the target using the mechanical advantages described above with reference to FIGS. 1(a)-3(b).

Referring to FIG. 8A, the syringe 500 is shown with the plunger 514 in the fully withdrawn position. It should be noted that the thread segment 514B is located at the second thread pitch 520F portion of the variable pitch thread 520C. When the plunger 514 is depressed, eg, to prime the syringe 500, the thread segment 514B crosses the second thread pitch 520F of the variable pitch thread 520C as shown in FIG. 8B, generally the first. Move into thread pitch 520E. During priming, air is typically expelled from barrel 540, possibly with a small amount of drug. It will be appreciated that as the thread segment 514B enters the first thread pitch 520E, the rotational speed of the screw 530 decreases due to the uniform axial movement of the plunger 514. In this way, the user can accurately prime the syringe 500 to the desired dosage. The user can then depress the plunger 512 or rotate the plunger dial 517 to deliver the primed dose, and the thread segment 514B rotationally translates into the screw 530 to deliver the medication. To rotate the variable pitch thread 520C relative to the first thread pitch 520E (see FIG. 8C). In this way, the syringe can be quickly filled and primed. For example, the pitch ratio of the first thread pitch 520E to the adapter nut may be 1:1. Therefore, when the thread segments 514B are arranged at the first thread pitch 520E, the axial translation of the plunger seal 536 is equal to the axial translation of the plunger 512. This allows the syringe to be run as a standard syringe during the filling and priming steps, providing a familiar experience for medical professionals. After priming, with the thread segment 514B positioned in the second thread pitch 520F, the syringe provides fine control of the volume of drug to be administered as described above with reference to FIGS. 1-7A(b). I will provide a.

Accordingly, one of ordinary skill in the art can adapt the variable pitch threads 520C to provide the desired rotation and thus axial movement of the screw 530 for relatively uniform axial movement of the plunger 512. Will be understood. Further, it will be appreciated that the variable pitch thread 520C can include more than two pitches. For example, variable pitch thread 520C can include three or more different pitches. The pitch can gradually transition from one pitch to another, along its entire length, such as a gradual transition from coarse to fine. Additionally, the variable pitch thread 520C can include transition pitches between different pitches, such as transition pitches between coarse and fine.

8A-9B show the housing 520 formed as a single piece, it will be appreciated that the housing 520 can be composed of multiple components. Those skilled in the art will further appreciate that a housing containing multiple components can not only facilitate manufacturing and assembly, but also enhance device customization options and functionality.

For example, the housing 520 can include a lower housing and an upper housing. For example, FIG. 15 illustrates an exemplary embodiment of the invention having a housing 520 that includes a lower housing 522 and an upper housing 524. The lower housing 522 and the upper housing 524 may include, for example, screw engagement, snap fit, interference fit, hook/protrusion and window engagement (as shown in the cross-sectional view of FIG. 15), or a wide variety of known methods. And can be assembled with each other. As shown in FIG. 15, the upper housing 524 can include one or more hooks 524A configured to engage one or more windows 522A of the lower housing 522. In yet another embodiment, the adapter 518 can be formed separately from the lower housing and assembled to the lower housing 522.

In addition to aiding in the manufacture and assembly of these components, bifurcating or even trifurcating the housing 520 into multiple components may have additional functional benefits. For example, the pitch ratio of the individual upper housing 524 and lower housing 522 can be varied to provide customization options to allow different precision or adjustment of dose delivery. Thus, the rest of the device may be of uniform construction, regardless of the dose accuracy parameter, but by changing or selecting the correct lower and upper housings, along with the mating threaded portion of the plunger rod, each The specifically desired dose accuracy of the device can be simply modified. Thus, the device can allow substantial customization while minimizing the components that need to be modified to meet the exact desired delivery parameters. Further customization can be provided, for example, by changing the pitch of the screws 530 and the internal threaded portion 518F of the adapter 518. In such a configuration, the adapter 518 may be formed with the lower housing 522 as shown, or formed separately from the lower housing 522 and assembled to the lower housing 522. In this way, the device can be further customized by changing the adapter 518 and screws 530. Those skilled in the art will provide a wide range of options for customizing the device by utilizing a number of standardized components that such configurations can be mixed and matched to provide the desired delivery parameters. It will be understood that you can. Modifying these components may also allow the manufacturer, drug company or user to modify other parameters such as drug delivery metering, applied force and filling volume, which This is because all depend at least in part on the selected pitch ratio of these sub-components.

Similarly, the functionality of one or more components may be further separated into separate sub-components. For example, the housing can be further subdivided such that the upper housing has an inner upper housing and an outer upper housing. The inner upper housing in such cases includes a threaded portion and can mate with the outer upper housing. This may further aid in the manufacture and assembly of the device, and/or the extent of customization of the device may be extended by replacement of only one subcomponent. In this example, the inner upper housing can be easily replaced to change the threading, and thus the accuracy or adjustment of drug delivery. Additionally or alternatively, one or more components may be modified to provide or complement the functionality of another component described herein, or a function similar thereto. .. For example, in at least one embodiment, cover 516 can be modified to incorporate a threaded portion that complements the threaded portion of the upper housing. This can be utilized to provide additional axial translation of the plunger and/or can be utilized to provide another portion of the plunger with a modified pitch ratio. In yet another embodiment of the invention, the threaded cover is elongated and mated with the inner upper housing such that the cover has a threaded portion that extends substantially the length of the housing or upper housing. be able to. Thus, the threaded portion of the housing can be a separate component from the outside of the housing. As a result, the threaded portion can be easily replaced.

Further, the threaded portion of the device and/or the subcomponents of the device can have any range of thread contours or cross-sectional configurations. For example, FIGS. 8A-9B show configurations that use a rectangular thread profile. The embodiment shown in FIGS. 10A(a)-11(b) illustrates a configuration utilizing a triangular thread profile. The term contour in this sense is intended to refer to the cross-sectional shape of each thread of the threaded portion of the device.

The thread profile or shape can be selected to meet the desired parameters of the functioning device. For example, the triangular thread profile may reduce the sliding force experienced by the user and allow for a less tacky engagement between corresponding threaded components. This may be because the engagement surface of the corresponding threaded component, which is more easily tactile or perceived to be manipulated by the user, changes or occurs in a different plane. Furthermore, the triangular thread profile can allow more rotation with smaller axial lengths. This can provide finer precision, regulation or volume control for the device. Thus, while embodiments of the present invention exhibit rectangular/square thread profiles or triangular square profiles, the present device allows the use of many thread profiles while still within the scope of the claimed invention herein. can do. Similarly, the thread direction can be varied while still being within the scope of the claimed invention herein.

In the embodiment shown in FIGS. 10A(a)-14, the dose control mechanism 610 further includes a housing 620 having at least a first housing 668 and a second housing 670, the first housing 668 and the second housing 670 comprising: It is adapted to selectively telescopically move relative to each other between a retracted position and an extended position. As such, the dose control mechanism 610 can be provided in the retracted position and then extended to retract the medication into the barrel. In at least one embodiment, the first housing 668 and the second housing 670 can then be translated with respect to each other to a priming position from which the medication can be administered. A first such embodiment is shown in FIGS. 10A(a)-11(b), and a second such embodiment is shown in FIGS. 12A(a)-14. The difference between the first such embodiment and the second such embodiment is the mechanism that manages the relative movement between the first housing portion 668 and the second housing portion 670. Therefore, the same reference numbers are utilized for similar components between the two embodiments. Those skilled in the art will couple the illustrated dose control mechanism 600 of FIGS. 12A(a)-12B(e) to the barrel of a syringe similar to the embodiment of FIGS. 10A(a)-10C(f). It will be appreciated that it is possible.

More specifically, in the illustrated embodiment, the second housing portion 670 is disposed between the first housing portion 668 and the plunger 614. In such an embodiment, the second housing portion 670 includes an internal thread 670D, which may be either constant pitch or variable pitch, configured to engage the external thread segment 614B of the plunger 614. The second housing portion 670 is configured to be axially translatable with respect to the first housing portion 668 in the first configuration. In the second configuration, the sleeve 670 is fixed relative to the first housing portion 668. As described below, this allows the first housing portion 668 and the second housing portion 670 to move in a manner familiar to the user when moving from the retracted position to the extended position and then to the priming position. Can be rapidly filled and primed while providing accurate dose control during delivery.

To fill the syringe, the user pulls the button 612 proximally. This causes the plunger 614, the second housing portion 670, the screw 630, the plunger rod 634 and the plunger seal 636 to move proximally with respect to the first housing portion 668 from the retracted position shown in FIGS. 12A(a) and 13A. 10A(a), 10A(b), 12A(b), 13B translates to the extended position, thereby withdrawing the fluid content into the barrel of the syringe. After filling the syringe, the user can prime the syringe by depressing button 612 distally. As a result, the plunger 614, the second housing portion 670, the screw 630, the plunger rod 634, and the plunger seal 636 move as a unit to discharge a part of the fluid contained in the barrel (FIGS. 10B(c) and 10B). (D) and FIG. 12B(c) show this position). When this priming movement is complete, the second housing portion 670 engages the first housing portion 668, which prevents the second housing portion 670 from rotating or translating with respect to the first housing portion 668. .. In this configuration, the dose control mechanism functions similarly to the embodiment described above with reference to Figures 1(a)-7A(b).

10A(a)-11(b) illustrate one embodiment of a locking mechanism that limits relative movement of the second housing portion 670 relative to the first housing portion 668. The second housing portion 670 can include a guide boss 670A and a locking tab 670B. The first housing portion 668 can include a longitudinal slot 668H. As shown in FIG. 10A(b), as the second housing portion 670 translates proximally to fill the syringe, both the guide boss 670A and the locking tab 670B are positioned within the longitudinal slot 668H. It This limits rotation of the second housing portion 670 relative to the first housing portion 668. As shown in FIG. 10B(d), as the second housing portion 670 translates distally, eg, to prime the syringe, the locking tab 670B follows the second housing portion 670 relative to the first housing portion 668. Engaged with the first housing portion 668 so as to limit translation. Additionally or alternatively, the interaction of guide boss 670A with longitudinal slot 668H may limit distal translation of second housing portion 670 relative to first housing portion 668.

In at least one embodiment shown in FIGS. 12A(a)-14, the second housing portion 670 has a track 672 that engages a guiding aspect of the first housing portion 668. Initially, the guide feature 668G is located on the first portion 672A of the track 672, as shown in FIG. 13A. Interaction of guide feature 668G and track 672 as plunger 614, second housing portion 670, screw 630, plunger rod 634 and plunger seal 636 translate in the proximal direction from the retracted position of FIGS. 12A(a) and 13A. This causes the second housing portion 670 to rotate relative to the first housing portion 668 to the position shown in FIGS. 12A(b) and 13B. That is, in addition to translating axially, the second housing portion 670 rotates relative to the first housing portion 668. Thereafter, distal translation of the second housing portion 670 relative to the first housing portion 668 causes the second housing portion to move from the extended position shown in FIGS. 12A(b) and 13B to the priming position shown in FIGS. 12B(c) and 13C. When translated, the guide feature 668G crosses the second portion 672B of the track 672. The track 672 can include a locking feature 672C that engages the guiding feature to limit further translation of the second housing portion 670 relative to the first housing portion 668.

The rotation of the second housing portion 670 and the plunger 614 may be coupled during the filling and priming steps to prevent relative rotation therebetween. For example, as shown in FIGS. 12A(a)-14, the dose control mechanism 610 can include a coupler 680 in a locked relationship with the plunger 614. During the filling and priming steps, the tabs 680A of the fitting 680 can be positioned within the notches 670F of the second housing portion 670, thereby allowing rotation of the second housing portion 670 relative to the fitting 680. Can be restricted. This engagement also prevents rotation of the second housing portion 670 relative to the plunger 614 due to the tight relationship of the coupler 680 and the plunger 614. The user can separate the tab 680A of the coupler 680 from the notch 670F of the second housing portion 670 by translating the coupler 680 proximally (FIGS. 12B(c) and 12B(d). ) Please compare). With the coupler 680 in this position, the dose control mechanism can be operated as described above, with the plunger 614 relative to the housing 620 and the tab 680A resting along the upper sloped surface of the housing 620. Can be rotated to rotate the screw 630 to expel the contents of the syringe barrel. The remaining elements of the dose control mechanism 610 of FIGS. 12A(a)-14 are substantially as shown in FIGS. 10A(a)-11(b).

In any of the described embodiments, the dose control mechanism can include one or more additional threading components. This can provide the user with additional mechanical advantages. For example, the dose control mechanism can include an inner plunger and an outer plunger. The outer plunger has an external thread that engages with the internal threads of the housing and an internal thread that engages with the external threads of the inner plunger. The inner plunger also has internal threads that engage the threads. In this way, the ratio of displacement between the knob and the plunger seal can be increased.

According to yet another feature, some embodiments can provide tactile feedback to a user, eg, in connection with confirming a desired delivery volume. Thus, when the user dials the plunger rod/screw to his or her desired dose volume (eg, rotating the plunger 514 until a particular microliter setting is visible in the window 520A), the user Feel a tactile notch or stop that signals positioning relative to a preset dose volume. The dose control mechanism 510 can be provided with multiple volume-based detents to indicate different dose volumes. By way of example only, the dose control mechanism 510 can include such feedback for syringe delivery volumes of 20 microliters, 10 microliters and 5 microliters.

Although any suitable configuration may provide haptic feedback, one such embodiment is shown in FIGS. 16(a)-16(c). For example, housing 520 and plunger 514 can include structures that provide tactile feedback when aligned. As shown most clearly in FIG. 16(c), the housing 520 can include a protrusion 526 and the plunger 514 can include at least one recess 514B that, when aligned, can be used by the user. In contrast, it provides a variation of the normal rotation of plunger 514.

The recess 514B of the plunger 514 can be formed by any suitable method. For example, the recess 514B can be formed by a depression or a bore extending through the wall of the plunger 514.

Similarly, the protrusion 526 may be provided by any suitable structure, such as a molding composition on the inner wall of the housing 520. However, in the illustrated embodiment, the housing 520 includes at least one radially extending aperture 520G, through which the projection extends radially inward to provide a protrusion 526. In this embodiment, a pair of apertures 520G and a pair of protrusions 526 are provided. As shown in FIGS. 16( a )- 16 (c ), the protrusion 526 can extend from a separate clip 528 that can be attached to the outer surface of the housing 520.

Any number of such clips 528 may be provided at locations along the length of the housing 520 to identify a corresponding number of desired set/stop points that identify the preset dose volume. Be understood. Alternatively or additionally, plunger 514 may be provided with any number of recesses 514B corresponding to a preset dose volume. When the user axially rotates the plunger rod/screw to dial his desired delivery volume, the projection 526 extending radially from the clip 528 corresponds to the defined set point/stop point. Contact/engage with recess 514B. Recess 514B and protrusion 526 are each sized to match a preset dose volume within the syringe for drug delivery.

Any of the dose control mechanisms described above can be used with such mixing syringes. The dose control mechanisms described herein allow proximal translation of the plunger rod relative to the drug container, so that they are particularly suitable for such mixing syringes.

Thus, the novel embodiments of the present invention provide a dose control mechanism that enables accurate dosing and delivery of drug therapeutics, and a drug delivery syringe that incorporates such a control mechanism. These new devices allow confirmation and control of dosage within a device size similar to commonly used conventional syringes all available on the market, and “priming” the syringe prior to drug delivery (ie , Air bubbles), ensuring accurate delivery of microliter volumes of medication. These new devices are safe and easy to use, and are aesthetically and ergonomically attractive to clinicians. The novel device of the present invention provides these desirable features without any of the problems associated with known prior art devices.

Many known filling processes and equipment can be utilized to accomplish the filling step of the syringe manufacturing process. Barrel assemblies, needles, plunger seals, plunger rods, and other components described in their manufacturing and assembly processes may be as described above or may perform the same function as these components. It can be many similar components. Throughout the specification the aim has been to describe the preferred embodiments of the invention without limiting the invention to any one embodiment or specific collection of features. Various modifications and changes can be made to the described and illustrated embodiments without departing from the invention. The disclosures of each patent and scientific literature, computer program, and algorithm referred to herein are hereby incorporated by reference in their entirety.

Many known filling processes and equipment can be utilized to accomplish the filling step of the syringe manufacturing process. Barrel assemblies, needles, plunger seals, plunger rods, and other components described in their manufacturing and assembly processes may be as described above or may perform the same function as these components. It can be many similar components. Throughout the specification the aim has been to describe the preferred embodiments of the invention without limiting the invention to any one embodiment or specific collection of features. Various modifications and changes can be made to the described and illustrated embodiments without departing from the invention. The disclosures of each patent and scientific literature, computer program, and algorithm referred to herein are hereby incorporated by reference in their entirety.
Example 1. A dose control mechanism for a syringe,
A housing having a longitudinally extending channel having an inner surface;
An adapter including a channel having a fine thread,
A plunger having an outer surface and an axially extending channel, the axially extending channel including a first key feature;
A screw having a threaded outer surface, the proximal end of the thread being at least partially disposed within the axially extending channel of the plunger, the threaded outer surface being at a proximal end portion of the threaded outer surface. And a second key aspect, wherein at least a portion of the second key aspect is disposed within the axially extending channel of the plunger and engages the first key aspect for sliding movement. So that rotational movement of the plunger causes rotational movement of the screw such that a tip portion of the outer surface of the screw is at least partially disposed within the fine thread of the adapter and engages the fine thread. , Including fine threads, screws,
An engaging thread configuration including at least one thread segment and a pitch guide including a variable pitch thread, wherein at least a portion of the longitudinally extending channel of the housing comprises the pitch guide and the at least One of the thread segments, the plunger including the other of the pitch guide and the at least one thread segment, the plunger including the at least one thread segment and the pitch guide. An engaging thread configuration that is at least partially within the housing in an engaged state;
A dose control mechanism comprising.
Example 2. The variable pitch thread includes at least two different thread pitches,
The dose control mechanism described in Example 1.
Example 3. The housing includes the pitch guide,
The variable thread pitch changes from a coarse line on the base end side to the adapter to a relatively fine line on the base end side with respect to the coarse line,
The dose control mechanism according to Example 1 or 2.
Example 4. The variable pitch thread includes at least three different thread pitches,
The dose control mechanism according to any one of Examples 1-3.
Example 5. The variable pitch thread includes a transition between the at least two different thread pitches,
The dose control mechanism according to any one of Examples 1-3.
Example 6. The transition is gradual,
The dose control mechanism described in Example 5.
Example 7. The transition is present over substantially the entire length of the pitch guide,
The dose control mechanism described in Example 6.
Example 8. The variable pitch thread includes at least one length portion of constant thread pitch,
The dose control mechanism according to any one of Examples 1 to 6.
Example 9. The variable pitch thread includes coarse threads arranged on the distal side and relatively fine threads arranged on the proximal side,
The dose control mechanism according to any one of Examples 1-8.
Example 10. The pitch of the fine threads of the variable pitch thread is substantially equal to the pitch of the fine threads of the adapter,
The dose control mechanism described in Example 9.
Example 11. The housing includes at least a first housing portion and a second housing portion,
The dose control mechanism according to any one of Examples 1-10.
Example 12. The first housing portion is an upper housing,
The second housing portion is a lower housing,
The upper housing and the lower housing are coupled to each other,
The dose control mechanism described in Example 11.
Example 13. The first housing portion includes at least one thread pitch different from the thread pitch of the second housing portion,
The dose control mechanism according to Example 11 or 12.
Example 14. A dose control mechanism for a syringe,
A housing having a longitudinally extending channel having an inner surface, the housing having at least a first housing portion and a second housing portion arranged to telescopically move relative to each other between a retracted position and an extended position. Housing containing,
An adapter including a channel having a fine thread,
A plunger having an outer surface and an axially extending channel, the axially extending channel including a first key aspect;
A screw having a threaded outer surface, the proximal end of the thread being at least partially disposed within the axially extending channel of the plunger, the threaded outer surface being at a proximal end portion of the threaded outer surface. And a second key aspect, wherein at least a portion of the second key aspect is disposed within the axially extending channel of the plunger and engages the first key aspect for sliding movement. So that rotational movement of the plunger causes rotational movement of the screw such that a tip portion of the outer surface of the screw is at least partially disposed within the fine thread of the adapter and engages the fine thread. Screws, including fine threads,
An engaging thread configuration including at least one thread segment and a pitch guide including threads, wherein at least a portion of the longitudinally extending channel of the housing comprises the pitch guide and the at least one Including one of the thread segments, the plunger including the other of the pitch guide and the at least one thread segment, the plunger having the at least one thread segment engaging the pitch guide. An engagement thread configuration that is at least partially present within the housing in the
A dose control mechanism comprising.
Example 15. The first housing portion and the second housing portion are arranged to move between the extended position and the priming position,
The dose control mechanism described in Example 14.
Example 16. The plunger and the first housing part are adapted to be separated to allow rotational movement relative to each other when the first housing part and the second housing part are arranged in the priming position,
The dose control mechanism described in Example 15.
Example 17. The plunger and the first housing portion are coupled to prevent rotational movement relative to each other during telescopic movement from the extended position,
The dose control mechanism according to any one of Examples 14-16.
Example 18. The first housing portion and the second housing portion are arranged for controlled rotational movement relative to each other,
18. The dose control mechanism according to any one of Examples 14-17.
Example 19. The first housing portion and the second housing portion are adapted to be coupled to each other in the priming position to prevent relative movement therebetween.
19. The dose control mechanism according to any one of Examples 14-18.
Example 20. At least one of the first housing part and the second housing part wherein the relative movement of the first housing part and the second housing part between the retracted position and the extended position comprises at least one guiding feature. Managed by one and the other of said first housing part and said second housing part comprises at least one track,
20. The dose control mechanism according to any one of Examples 14-19.
Example 21. Movement of the guide feature on at least a portion of the track provides relative rotational movement between the first housing portion and the second housing portion.
The dose control mechanism described in Example 20.
Example 22. The engagement thread configuration results in rotation of the plunger within the housing as the plunger translates relative to at least a portion of the housing,
Rotation of the plunger within the housing provides rotation of the screw within the adapter channel,
Rotation of the screw in the adapter channel and engagement of the first and second key features causes relative axial sliding between the screw and the plunger and depression of the plunger. Movement of the screw in a distal direction relative to the adapter, and movement of the screw in a proximal direction when the plunger moves proximally with respect to at least a portion of the housing,
22. The dose control mechanism according to any one of Examples 1-21.
Example 23. At least a portion of the variable pitch threads has a coarser pitch than the fine threads of the adapter,
23. The dose control mechanism according to any one of Examples 1-22.
Example 24. Further comprising a detent based on one or more volumes,
The dose control mechanism according to any one of Examples 1 to 23.
Example 25. The one or more volume-based detents comprise a protrusion configured to engage a recess in the plunger;
The dose control mechanism described in Example 24.
Example 26. The adapter is adapted to be coupled to a barrel of a syringe,
The tip of the plunger is adapted to be coupled to a plunger rod located in the barrel,
The dose control mechanism according to any one of Examples 1 to 25.
Example 27. Precise dosing comprising a dose control mechanism according to any one of Examples 1-26, a barrel, a plunger rod, a plunger seal coupled to the plunger rod and disposed in the barrel, and a needle. Quantity of drug delivery syringe,
The proximal end of the plunger rod is coupled to the distal end of the screw,
A tip portion of the plunger rod is coupled to the plunger seal,
Syringe.
Example 28. At least one of a fill-in-use syringe, a drug-filled syringe and a safety syringe,
The syringe described in Example 27.

Claims (28)

A dose control mechanism for a syringe,
A housing having a longitudinally extending channel having an inner surface;
An adapter including a channel having a fine thread,
A plunger having an outer surface and an axially extending channel, the axially extending channel including a first key feature;
A screw having a threaded outer surface, the proximal end portion of the screw being at least partially disposed within the axially extending channel of the plunger, the threaded outer surface being at a proximal end portion of the threaded outer surface. And a second key aspect, wherein at least a portion of the second key aspect is disposed within the axially extending channel of the plunger and engages the first key aspect for sliding movement. So that rotational movement of the plunger causes rotational movement of the screw such that a tip portion of the outer surface of the screw is at least partially disposed within the fine thread of the adapter and engages the fine thread. , Including fine threads, screws,
An engaging thread configuration including at least one thread segment and a pitch guide including a variable pitch thread, wherein at least a portion of the longitudinally extending channel of the housing comprises the pitch guide and the at least one. One of the thread segments, the plunger includes the other of the pitch guide and the at least one thread segment, and the plunger includes the at least one thread segment with the pitch guide. An engaging thread configuration that is at least partially present in the housing in an engaged state;
A dose control mechanism comprising. The variable pitch thread includes at least two different thread pitches,
The dose control mechanism according to claim 1. The housing includes the pitch guide,
The variable thread pitch changes from a coarse line on the base end side to the adapter to a relatively fine line on the base end side with respect to the coarse line,
The dose control mechanism according to claim 1 or 2. The variable pitch thread includes at least three different thread pitches,
The dose control mechanism according to claim 1. The variable pitch thread includes a transition between the at least two different thread pitches,
The dose control mechanism according to claim 1. The transition is gradual,
The dose control mechanism according to claim 5. The transition is present over substantially the entire length of the pitch guide,
The dose control mechanism according to claim 6. The variable pitch thread includes at least one length portion of constant thread pitch,
The dose control mechanism according to any one of claims 1 to 6. The variable pitch thread includes coarse threads arranged on the distal side and relatively fine threads arranged on the proximal side,
The dose control mechanism according to any one of claims 1 to 8. The pitch of the fine threads of the variable pitch thread is substantially equal to the pitch of the fine threads of the adapter,
The dose control mechanism according to claim 9. The housing includes at least a first housing portion and a second housing portion,
The dose control mechanism according to any one of claims 1 to 10. The first housing portion is an upper housing,
The second housing portion is a lower housing,
The upper housing and the lower housing are coupled to each other,
The dose control mechanism according to claim 11. The first housing portion includes at least one thread pitch different from the thread pitch of the second housing portion,
The dose control mechanism according to claim 11 or 12. A dose control mechanism for a syringe,
A housing having a longitudinally extending channel having an inner surface, the housing having at least a first housing portion and a second housing portion arranged to telescopically move relative to each other between a retracted position and an extended position. Housing containing,
An adapter including a channel having a fine thread,
A plunger having an outer surface and an axially extending channel, the axially extending channel including a first key aspect;
A screw having a threaded outer surface, the proximal end portion of the screw being at least partially disposed within the axially extending channel of the plunger, the threaded outer surface being at a proximal end portion of the threaded outer surface. And a second key aspect, wherein at least a portion of the second key aspect is disposed within the axially extending channel of the plunger and engages the first key aspect for sliding movement. So that rotational movement of the plunger causes rotational movement of the screw such that a tip portion of the outer surface of the screw is at least partially disposed within the fine thread of the adapter and engages the fine thread. Screws, including fine threads,
An engaging thread configuration including at least one thread segment and a pitch guide including a thread, wherein at least a portion of the longitudinally extending channel of the housing comprises the pitch guide and the at least one Including one of the thread segments, the plunger including the other of the pitch guide and the at least one thread segment, the plunger having the at least one thread segment engaging the pitch guide. An engagement thread configuration that is at least partially present within the housing in the
A dose control mechanism comprising. The first housing portion and the second housing portion are arranged to move between the extended position and the priming position,
The dose control mechanism according to claim 14. The plunger and the first housing part are adapted to be separated to allow rotational movement relative to each other when the first housing part and the second housing part are arranged in the priming position,
The dose control mechanism according to claim 15. The plunger and the first housing portion are coupled to prevent rotational movement relative to each other during telescopic movement from the extended position,
The dose control mechanism according to any one of claims 14 to 16. The first housing portion and the second housing portion are arranged for controlled rotational movement relative to each other,
The dose control mechanism according to any one of claims 14 to 17. The first housing portion and the second housing portion are adapted to be coupled to each other in the priming position to prevent relative movement therebetween.
The dose control mechanism according to any one of claims 14 to 18. At least one of the first housing part and the second housing part wherein the relative movement of the first housing part and the second housing part between the retracted position and the extended position comprises at least one guiding feature. Managed by one and the other of said first housing part and said second housing part comprises at least one track,
A dose control mechanism according to any one of claims 14 to 19. Movement of the guide feature on at least a portion of the track provides relative rotational movement between the first housing portion and the second housing portion.
The dose control mechanism according to claim 20. The engagement thread configuration results in rotation of the plunger within the housing as the plunger translates relative to at least a portion of the housing,
Rotation of the plunger within the housing provides rotation of the screw within the adapter channel,
Rotation of the screw in the adapter channel and engagement of the first and second key features causes relative axial sliding between the screw and the plunger and depression of the plunger. Movement of the screw in a distal direction relative to the adapter, and movement of the screw in a proximal direction when the plunger moves proximally with respect to at least a portion of the housing,
A dose control mechanism according to any one of claims 1 to 21. At least a portion of the variable pitch threads has a coarser pitch than the fine threads of the adapter,
A dose control mechanism according to any one of claims 1 to 22. Further comprising a detent based on one or more volumes,
The dose control mechanism according to any one of claims 1 to 23. The one or more volume-based detents comprise a protrusion configured to engage a recess in the plunger;
The dose control mechanism according to claim 24. The adapter is adapted to be coupled to a barrel of a syringe,
The tip of the plunger is adapted to be coupled to a plunger rod located in the barrel,
The dose control mechanism according to any one of claims 1 to 25. 27. An accurate dose control mechanism according to any one of claims 1 to 26, a barrel, a plunger rod, a plunger seal coupled to the plunger rod and disposed in the barrel, and a needle. A dose of drug delivery syringe,
The proximal end of the plunger rod is coupled to the distal end of the screw,
A tip portion of the plunger rod is coupled to the plunger seal,
Syringe. At least one of a fill-in-use syringe, a drug-filled syringe and a safety syringe,
The syringe according to claim 27.