Patent Description:
Prior to discharge, the pre-filled syringe often contains the medicament in a dischargeable form or, alternatively, in a form requiring conversion to the dischargeable form. The conversion often involves mixing together medicament components initially maintained apart within the syringe.

Prior to discharge, the dischargeable form of the medicament is often contained within the syringe between a slideable syringe plunger and a distal inner end of the syringe defining a discharge orifice, the plunger sealing circumferentially against an interior wall of the syringe.

A seal may require force to be dislodged from the interior wall if static friction is substantial. If the force is applied by a longitudinal impulse, such as a push by an operator's thumb, the impulse may provide enough energy to dislodge the seal, but may also compromise the operator's control over the displacement of the plunger once the seal is dislodged.

With the syringe oriented distal end up, discharge of air from the syringe ("priming") may be effected by displacement of the plunger toward the distal inner end. Priming drives the air out through the discharge orifice and a distally attached delivery needle, thus filling the needle with the medicament.

After priming, before initiation of delivery of the medicament, the needle is inserted into the patient. Delivery of the medicament is effected by further displacement of the plunger toward the distal inner end. An extent of displacement of the plunger toward the distal inner end determines a volume of medicament delivered to the patient.

Typically, the extent of the plunger displacement delivering the medicament ("delivery stroke") is limited by the plunger "bottoming out" against the distal inner end. Bottoming out typically involves deformation of a pliant material of the plunger, often against the distal inner end, which may include a pliant material of a needle-penetrated distal stopper.

The extent of the delivery stroke and, thereby, the volume of medicament delivered are often sensitive to deformation of the plunger and/or the stopper. Extent of such deformation is often not reliably repeatable. Bottoming out may not provide a reliable delivery mechanism for low volume of the medicament.

Operator manipulation to effect stages of syringe operation - such as mixing, priming or delivery - impacts volume of medicament remaining in the syringe at initiation of delivery. Typically, there is little or no feedback indicating to an operator when, during the manipulation, pre-delivery stages have been completed and when to initiate delivery. Without such indication of progress of stages of syringe operation, medicament to be delivered may be lost before initiation of delivery. Alternatively, the volume of medicament remaining in the syringe after pre-delivery stages may exceed a desired delivery volume. For low volume delivery, such loss or excess of medicament may represent a significant portion of the desired volume.

It would be desirable, therefore, to provide apparatus and methods for low volume medicament delivery with improved reliability over bottoming out.

It would also, therefore, be desirable to provide apparatus and methods for increasing the operator's control over the plunger displacement while dislodging the seal from the container wall.

Also, it would be desirable, therefore, to provide apparatus and methods providing indication of progress of stages of syringe operation.

<CIT> discloses a medicament delivery device including a body having a proximal end and a distal end. At the distal end, the device comprises a distal housing part for receiving a medicament container. The device further comprises a dose setting drum for setting a dose when being rotated in a first direction, and for delivering a dose when being rotated in a second direction.

<CIT> discloses an auto-injector for delivering a medicament. The auto-injector comprises an elongate housing for containing a syringe having an injection needle and a stopper. The syringe is slidably arranged with respect to the housing. The auto-injector further comprises a compression spring for pushing the injection needle from a covered position inside the housing into an advanced position for insertion into the injection site. To achieve this, a trigger button of the auto-injector axially moves a thrust collar to compress the drive spring to apply load from the drive spring to the syringe and/or the stopper for needle insertion and injection.

<CIT> discloses a medicament delivery device for delivering metered doses of a medicament in accordance with the preamble of independent claim <NUM>.

The objects and advantages of the invention will be apparent upon consideration of the following detailed description, taken in conjunction with the accompanying drawings, in which like reference characters refer to like parts throughout, and in which:.

In one aspect, the present invention is directed to a medicament delivery device, the device being specified by the features of independent claim <NUM>. Optional additional features of the device according to the invention are specified in the dependent claims directed to the device.

In another aspect, the present invention is directed to a method of manufacturing a medicament delivery device, the method being specified by the features of independent claim <NUM>. Optional additional features of the method according to the invention are specified in the dependent claims directed to the method.

Exemplary embodiments are shown and described below. Features, including structures, materials, volumes, functions and other attributes that are shown and described in connection with any of the embodiments may be combined, in whole or in part, with each other or included, in whole or in part, in other embodiments.

The device is suitable for the delivery of a predetermined low volume of medicament. The predetermined low volume of medicament may include a predetermined amount of the medicament. The predetermined low volume of medicament may include a target amount of the medicament. The delivery involves a syringe delivery stroke. The delivery stroke involves distal displacement of the medicament by a plunger rod.

The operator may distally displace the rod through a plunger rod guide. The guide may include a boss.

Hardness of materials of the rod and of the guide over materials of the plunger may facilitate reliable setting of the delivery stroke and, thus, of the volume of delivered medicament, without volume uncertainties that may be associated with bottoming out of the plunger.

The device may provide the operator indication of progress of stages of syringe operation, such as initiation and/or completion of stages of rod displacement, including the delivery stroke and pre-delivery stages such as priming.

The device defines a longitudinal axis. The longitudinal axis defines a proximal direction and a distal direction. The longitudinal axis defines a radial direction normal to the longitudinal axis. The longitudinal axis defines a circumferential direction about the longitudinal axis. The device has a distal end.

The device includes the plunger rod. The device includes a knob. The knob may include any suitable material, including that referred to above in connection with the rod. The knob is disposed at a proximal end of the device. The knob is attached to the rod.

The knob may have a cross-section transverse to the axis. The cross-section may be circular. The cross-section may be elliptical. The cross-section may be of any suitable shape. Any suitable shape may include a polygonal shape. The cross-section may be bordered by a perimeter.

The knob may include turn ridges along the perimeter. The turn ridges may facilitate traction on the knob. The turn ridges may facilitate gripping the knob. The turn ridges may facilitate turning the knob.

The knob may include a proximal end of the knob. The proximal end may include push features. The push features may facilitate pushing the rod. The push features may facilitate traction on the knob. The push features may include a push pad. The push pad may be smoothly contoured. The push features may include push ridges. The push ridges may be concentric about the axis.

The guide may support the boss. The boss may be of a shape that is, at least in part, cylindrical, cubic, pyramidal, tetrahedral, ellipsoidal, hemispherical or any other suitable shape. Any other suitable shape may include prismatic. Any other suitable shape may include an irregular form of any of the listed shapes. Any other suitable shape may include a truncated form of any of the listed shapes. Any other suitable shape may include a combination of two or more of any of the listed shapes. The combination may include dome-capped cylindrical. The combination may include rounded-apex stepped tetrahedral.

The device may include a housing. The housing may be disposed coaxial with the longitudinal axis. The housing may be disposed, relative to the longitudinal axis, distal-to-proximal parallel to the device. The housing may define an opening. The opening may be disposed proximally on the housing. The opening may be a proximal housing opening. The guide may be disposed in the proximal housing opening.

The guide may be part of the housing. The guide may be manufactured as part of the housing. Manufacture of the guide as part of the housing may be accomplished through a molding process. Manufacture of the guide as part of the housing may be accomplished through an injection molding process. Manufacture of the guide as part of the housing may be accomplished through an overmolding process. The manufacture of the guide as part of the housing may be accomplished through a coinjection process.

The guide may be separate from the housing. The guide may be manufactured separately from the housing. The guide may be molded separately from the housing. The guide may be affixed to the housing. The guide may include guide-anchoring elements. The housing may include guide-anchor-accepting elements structurally complementary to the guide-anchoring elements. The guide may be affixed to the housing by mating the guide-anchoring elements with the guide-anchoring-accepting elements.

The device may include a medicament container. The container may be disposed in the housing. The container may be disposed distal the guide. The container may define a bore. The bore may be bound by an interior wall. The interior wall may define a substantially uniform diameter along a segment of the interior wall.

The rod may be configured to be displaced distally, relative to the housing, within the bore to discharge medicament from the container. The rod may be displaced distally until the boss abuts the terminal surface of the track.

The track may include the terminal surface. The track may support the terminal surface. The track may support the terminal surface proximally to the trigger. The terminal surface may be a distal surface of a proximal end-wall of the track. The end-wall may be a sidewall of the track. The end-wall may be orthogonal to the side of the track. The end-wall may be orthogonal to the running surface of the track. The end-wall may block relative proximal movement, beyond the distal surface of the end-wall, of the boss along the track.

Abutment of the boss against the terminal surface may substantially limit motion of the rod in a distal direction. The track may include sidewalls. The sidewalls adjacent the terminal surface may substantially limit motion of the rod in a distal direction when the boss abuts the terminal surface. Track sidewalls adjacent to the terminal surface may substantially limit motion of the rod in a circumferential direction when the boss abuts the terminal surface. Track sidewalls distal to the terminal surface may substantially limit motion of the rod in a distal direction when the boss abuts the terminal surface. Track sidewalls distal to the terminal surface may substantially limit motion of the rod in a circumferential direction when the boss abuts the terminal surface.

Abutment of the boss against the terminal surface may substantially limit motion of the rod, subsequent to the abutting, to movement in a proximal direction away from the boss. The boss abutting the terminal surface may limit motion of the boss, relative to the rod, to movement substantially axially away from the terminal surface.

The segment of the interior wall may include a distal portion. The distal portion may, in operation of the device, contact a bulk liquid residuum of the medicament after the boss abuts the terminal surface. The distal portion may be wetted by the bulk liquid residuum even after the boss abuts the terminal surface. The distal portion may directly contact the residuum. The distal portion may directly contact the residuum even after the boss abuts the terminal surface.

The device may include the plunger. The plunger may be at least one plunger slideably sealing against the interior wall. The plunger may be disposed within the container. The plunger may be disposed distal the rod. The plunger may be configured to slide distally responsive to distal displacement of the rod.

The device may include the stopper. The stopper may seal a distal end of the container. The distal end of the container may define a distal container opening. A proximal body-section of the distal stopper may be disposed within the distal container opening. The proximal body section of the distal stopper may seal against the interior wall of the container proximal to the distal container opening.

The stopper may include a distal surface. The distal surface may be disposed transverse to the axis. A distal body-section of the stopper proximal to the distal surface of the stopper may have an outer diameter greater than an outer diameter of the distal end of the container. A proximal rim of the distal body-section of the stopper may seal against an end-wall of the container surrounding the distal container opening.

The housing may include a distal retaining ridge. The distal retaining ridge may be disposed transverse to the axis. The distal retaining ridge may be part of an interior of a wall of the housing. The distal retaining ridge may be proximal to a distal end-wall of the housing surrounding a distal opening of the housing. The distal opening of the housing may be a distal housing opening. The distal housing opening may have an inner diameter. The inner diameter of the distal housing opening may be smaller than an outer diameter of the distal body-section of the distal stopper. The outer diameter of the distal body-section of the distal stopper may be substantially the same as an outer diameter of the container. The outer diameter of the container may be smaller than an inner diameter of the housing proximal to the distal retaining ridge. The container, with the distal end of the container sealed by the distal stopper, may be disposed within the housing between a distal aspect of the guide and the distal retaining ridge.

Prior to discharge of the medicament, the medicament may be sealed within the container between the stopper and the at least one plunger. The stopper may be configured to be penetrated by a needle. The needle may have a cannula. The cannula may be configured to distally transfer medicament discharged from the container.

The cannula may be configured to transfer medicament directly through the needle to the patient.

The cannula may be configured to transfer medicament indirectly through the needle to the patient. The needle may be a first needle. The device may include a second needle. The cannula of the first needle may be configured to transfer medicament to the second needle. The second needle may be configured to transfer medicament directly to the patient. The device may include a filter. The filter may be an in-line filter. The filter may be disposed between the first needle and the second needle. The filter may receive medicament discharged from the cannula of the first needle. The filter may filter medicament discharged from the cannula of the first needle. The second needle may receive medicament filtered by the filter. The second needle may transfer the medicament filtered by the filter to the patient.

The medicament may include a formulation of one or more compounds. The compounds may include naturally occurring substances. The compounds may include substances derived from naturally occurring substances. The compounds may include synthetically produced substances. The compounds may include chimeric substances. The compounds may include engineered substances. The compounds may include humanized substances. The compounds may include substances produced by recombinant techniques. The compounds may include substances modified by recombinant techniques.

The compounds may include a drug accepted for therapeutic treatment of a patient. The compounds may include a substance used in a therapeutic protocol. The compounds may include a substance used in a diagnostic protocol. The compounds may include a substance used in an experimental protocol. The compounds may include a substance compatible for use with apparatus and methods of the invention.

The medicament may include any medical agent listed herein, either alone or in combination with one or more other listed medical agents or with one or more other, non-listed, medical agents. The medical agents may include anti-glaucoma medications, other ocular agents, neuroprotective agents, antimicrobial agents, anti-inflammatory agents (including steroids and non-steroidal compounds), and biological agents including hormones, enzymes or enzyme-related components, antibodies or antibody-related components, oligonucleotides (including DNA, RNA, short-interfering RNA, and other suitable oligonucleotides, such as antisense oligonucleotides), DNA/RNA vectors, viruses or viral vectors, peptides, and proteins. The medical agents may include anti-angiogenesis agents, including angiostatin, anecortave acetate, thrombospondin, vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors, and anti-VEGF drugs, such as ranibizumab (LUCENTIS°), bevacizumab (AVASTIN®), pegaptanib (MACUGEN®), sunitinib, and sorafenib, and any of a variety of known small-molecule and transcription inhibitors having an anti-angiogenesis effect; ophthalmic drugs, including glaucoma agents, such as adrenergic antagonists, including beta-blocker agents such as atenolol, propranolol, metipranolol, betaxolol, carteolol, levobetaxolol, levobunolol and timolol. The medical agents may include platelet-derived growth factor (PDGF) inhibitors and anti-PDGF drugs. The medical agents may include transformation growth factor (TGF) inhibitors and anti-TGF drugs. The medical agents may include anti-inflammatory agents including glucocorticoids and corticosteroids, such as betamethasone, cortisone, dexamethasone, dexamethasone <NUM>-phosphate, methylprednisolone, prednisolone <NUM>-phosphate, prednisolone acetate, prednisolone, loteprednol, medrysone, fluocinolone acetonide, triamcinolone acetonide, triamcinolone, beclomethasone, budesonide, flunisolide, fluorometholone, fluticasone, hydrocortisone, hydrocortisone acetate and rimexolone; and non-steroidal anti-inflammatory agents including diclofenac, flurbiprofen, ibuprofen, bromfenac, nepafenac, ketorolac, salicylate, indomethacin, naxopren, naproxen, piroxicam and nabumetone. The medical agents may include anti-cytokine agents; the medical agents may include anti-interleukin-<NUM> agents such as tocilizumab (ACTEMRA®). The medical agents may include anti-complement agents, including those targeting complement factor D (such as an anti-complement factor D antibody or an antigen-binding fragment thereof) such as lampalizumab, and those targeting complement factor H (such as an anti-complement factor H antibody or an antigen-binding fragment thereof). The medical agents may include angiopoietin-specific agents, such as an angiopoietin-<NUM> antibody or an antigen-binding fragment thereof. The medical agents may include human growth hormone. The medical agents may include any suitable medical agent.

The medicament may include one or more derivatives of any of the above-mentioned medical agents. The medicament may include advanced forms of any of the above-mentioned medical agents. The medicament may include mutated forms of any of the above-mentioned medical agents. The medicament may include combinations of any of the above-mentioned medical agents. The combinations may be incorporated into a multi-specific molecule. The multi-specific molecule may exhibit properties of its constituent parts. The multi-specific molecule may exhibit properties different from any if its constituent parts. The medicament may include depots, hydrogels and pegylated forms of any of the above medical agents. The medicament may include any suitable form of any of the above medical agents.

Prior to discharge of the medicament, the medicament may be stored within the container. The medicament may be stored in a dischargeable form of the medicament. The dischargeable form of the medicament may include all medical agents desired in a scenario - therapeutic, experimental or otherwise - for delivery, under desired conditions. Desired conditions may include therapeutic activity, medical agent concentration(s), viscosity, pH, ionic strength or any other suitable condition.

The medicament may be stored in a storage form of the medicament. The storage form of the medicament may require preparation of the medicament for discharge. The preparation of the medicament for discharge may include conversion of the medicament from the storage form of the medicament to the dischargeable form of the medicament.

The storage form of the medicament may include a first component. The first component may be stored in the medicament container. The storage form of the medicament may include a second component. The second component may be stored in the medicament container. The second component may be stored apart from the first component.

The first component may be a formulation of any of the above-mentioned medical agents. The second component may be a formulation of any of the above-mentioned medical agents. The first component may be a formulation that, upon mixing with the second component, adjusts conditions of the second component. The second component may be a formulation that, upon mixing with the first component, adjusts conditions of the first component. Conditions may include therapeutic activity, medical agent concentration(s), viscosity, pH and ionic strength.

The preparation of the medicament may include mixing the first component and the second component. A mixture of the first component and the second component may include the dischargeable form of the medicament.

The storage form of the medicament may include a lyophilized product that, when reconstituted, includes the dischargeable form of the medicament. Reconstitution of the lyophilized product may involve mixing the lyophilized product with a reconstituting solution. The lyophilized product may be the first component. The reconstituting solution may be the second component. The second component may be in a liquid state.

The device may include a rod-contacting face. The distal end of the rod may contact the rod-contacting face. The distal end of the rod may connect with the rod-contacting face. The distal end of the rod may couple with the rod-contacting face. The rod-contacting face may be distally displaced within the container in response to distal displacement of the rod within the container.

The at least one plunger may include a proximal plunger. The rod-contacting face may be associated with a proximal face of the proximal plunger. The proximal face of the proximal plunger may include the rod-contacting face. The proximal plunger may be distally displaced within the container in response to distal displacement of the rod-contacting face within the container. The proximal plunger may be distally displaced within the container in response to distal displacement of the rod within the container.

The at least one plunger may include a discharge plunger. The discharge plunger may be disposed within the container distal to the proximal plunger. There may be no other plunger within the container between the discharge plunger and the stopper.

Prior to the mixing of the first component and the second component, the first component and the second component may be separated by the discharge plunger. The first component may be sealed within the container between the stopper and the discharge plunger. The second component may be sealed within the container between the discharge plunger and the proximal plunger.

The container may include a bypass feature. The bypass feature may be configured to facilitate fluid communication bypassing a sealing surface of the discharge plunger. The bypass feature may include one or more grooves, at least partly longitudinal with respect to the axis, recessed into the interior wall. Prior to mixing, the sealing surface of the discharge plunger may be disposed proximal to a proximal-most aspect of the bypass feature, sealing against the interior wall and maintaining the second component apart from the first component.

The mixing may involve orienting the device with its distal end up and penetrating the stopper to dispose the cannula through the stopper. The mixing may involve distal displacement of the rod-connecting face via distal displacement of the rod. Distal displacement of the rod-connecting face may distally displace the proximal plunger. Distal displacement of the proximal plunger may distally displace the second component. Distal displacement of the second component may distally displace the discharge plunger. Distal displacement of the discharge plunger may slide a proximal-most circumferential portion of the sealing surface of the discharge plunger along the interior wall to a position just distal to the proximal-most aspect of the bypass feature, facilitating distal flow along the bypass feature of the second component into the first component. Further distal displacement of the proximal plunger may not substantially displace the discharge plunger while the second component remains between the proximal plunger and the discharge plunger. While the second component remains between the proximal plunger and the discharge plunger, distal displacement of the proximal plunger may distally displace the second component along the bypass feature, facilitating mixing of the second component with the first component.

A distal face of the proximal plunger may be complementary to a proximal face of the discharge plunger. Upon encounter of the distal face of the distally displaced proximal plunger with the proximal face of the discharge plunger, substantially no second component may remain between the proximal plunger and the discharge plunger. When substantially no second component remains between the proximal plunger and the discharge plunger, the mixture may include the dischargeable form of the medicament.

When substantially no second component remains between the proximal plunger and the discharge plunger, further distal displacement of the proximal plunger may further distally displace the discharge plunger. A distal face of the discharge plunger may, upon being distally displaced toward the stopper, distally displace the dischargeable form of the medicament.

A scenario in which the medicament is stored during device manufacture in the storage form may be accommodated by a configuration of the device in which the at least one plunger includes the proximal plunger and the discharge plunger and in which the container includes the bypass feature. Such a configuration of the device may be termed a mixing configuration. In the mixing configuration, the rod-contacting face may be associated with the proximal plunger.

A scenario in which the medicament is stored during device manufacture in the dischargeable form may require, in the container, neither multiple plungers for sequestration of storage form components nor the bypass feature for mixing of components. When no mixing is to be performed, the plunger may include only the discharge plunger. A configuration of the device in which the plunger is the discharge plunger and in which the interior wall does not include the bypass feature, may be termed a non-mixing configuration. In the non-mixing configuration, the rod-connecting face may be associated with the discharge plunger. The rod-contacting face may be associated with a proximal face of the discharge plunger. The proximal face of the discharge plunger may include the rod-contacting face. The discharge plunger may be distally displaced by distal displacement of the plunger rod contacting the proximal face of the discharge plunger.

The device may be manufactured as a "pre-filled" device. The device may be manufactured with the container configured to store the predetermined low volume of the medicament. The volume may be substantially determined during manufacture. The volume may be set with anticipation of loss of medicament that may result from manipulations of the device prior to performance of the delivery stroke. Such manipulations may include mixing and priming. The volume may depend on the scenario for which the device is intended. Illustrative ranges of value of the volume may include about <NUM> milliliter to about <NUM> milliliter, about <NUM> milliliter to about <NUM> milliliter, about <NUM> milliliter to about <NUM> milliliter, about <NUM> milliliter to about <NUM> milliliter, about <NUM> milliliter to about <NUM> milliliter, about <NUM> milliliter to about <NUM> milliliters, about <NUM> milliliters to about <NUM> milliliters, about <NUM> milliliters to about <NUM> milliliters, about <NUM> milliliters to about <NUM> milliliters, about <NUM> milliliters to about <NUM> milliliters, about <NUM> milliliters to about <NUM> milliliters, about <NUM> milliliters to about <NUM> milliliters, about <NUM> milliliters to about <NUM> milliliters, about <NUM> milliliters to about <NUM> milliliters, or any other suitable ranges.

The housing may include a housing wall. The housing wall may be configured to deflect in response to deflection of the guide. The housing wall may include a section that is displaced radially relative to the longitudinal axis during the deflection of the guide. The section may be a first section. The housing wall may include a second section that is displaced radially relative to the longitudinal axis during the deflection of the guide. Radial direction of displacement of the section or sections relative to the longitudinal axis may conform to radial direction of the deflection of the guide relative to the longitudinal axis. The displacement of the section or sections may be radially outward. The displacement of the section(s) may be radially inward.

The device may include a finger flange. The finger flange may be part of the housing. The finger flange may be manufactured as part of the housing. Manufacture of the finger flange as part of the housing may be accomplished through a molding process. Manufacture of the finger flange as part of the housing may be accomplished through an injection molding process. Manufacture of the finger flange as part of the housing may be accomplished through an overmolding process. The manufacture of the finger flange as part of the housing may be accomplished through a coinjection process.

The finger flange may be separate from the housing. The finger flange may be manufactured separately from the housing. The finger flange may be molded separately from the housing. The finger flange may be affixed to the housing. The finger flange may have finger flange-anchoring elements. The housing may have finger flange-anchor-accepting elements structurally complementary to the finger flange-anchoring elements. The finger flange may be affixed to the housing by mating the finger flange-anchoring elements with the finger flange-anchoring-accepting elements.

The delivery stroke may be predetermined during the manufacture of the device. Mechanical properties of the materials of, and manufactured configuration of, the container and its associated stopper and plunger(s) and of the housing, guide and rod, may determine the delivery stroke. The full extent of the delivery stroke may be predetermined in manufacturing.

The method of manufacturing includes providing the rod. Providing the rod may include molding the rod. The rod may be configured to be displaced within the housing toward a distal end of the housing. The rod may support a terminal surface, such that, with the boss engaging the rod at the track and with the boss abutting the terminal surface, the boss may provide a reactive surface that limits further distal displacement of the rod. With the boss abutting the terminal surface, movement of the boss relative to the rod may be limited to substantially axial movement away from the terminal surface. With the boss engaging a longitudinal tract of the track, the boss may provide a reactive surface that limits rotational movement of the rod about the axis. The boss may engage the track by extending radially into the track. The boss may be engaged with the longitudinal tract by extending radially into the longitudinal tract.

The materials may be elected for their material properties. The material properties for which the materials may be elected may facilitate operation of the device. Material properties that facilitate operation of the device may include chemical inertness, resilience, transparency and other suitable properties. Other suitable properties may include hardness.

The plunger or plungers may include a plunger material. The plunger material may include polymeric material. The plunger material may include elastomeric material. The plunger material may include thermoplastic elastomer (TPE). The plunger material may include natural rubber. The plunger material may include a compound made from natural rubber. The plunger material may include synthetic rubber. The plunger material may include a compound made from synthetic rubber. The plunger material may include silicone rubber. The plunger material may include a compound made from silicone rubber. The plunger material may include butyl rubber. The plunger material may include a compound made from butyl rubber. The plunger material may include a material elected to reduce interaction of the plunger or plungers with the medicament. The plunger material may include a resilient material. The plunger material may include a material with a hardness less than about <NUM> Shore A durometer (ASTM D2240 type A hardness scale). The plunger material may facilitate movement of the plunger or plungers within the container. The plunger material may facilitate engagement of the plunger or plungers with the inner wall of the container. The plunger material may facilitate sealing of the plunger or plungers against the inner wall of the container.

The plunger material may include a plunger lubricious coating. The plunger lubricious coating may coat the plunger material. The plunger material may bear the plunger lubricious material. The plunger lubricious material may include polytetrafluoroethylene (PTFE). The plunger lubricious material may include ethylene tetrafluoroethylene (ETFE). The plunger lubricious coating may include a material elected to reduce interaction of the plunger or plungers with the medicament. The plunger lubricious material may facilitate movement of the plunger or plungers within the container. The plunger lubricious material may facilitate engagement of the plunger or plungers with the inner wall of the container. The plunger lubricious material may facilitate sealing of the plunger or plungers against the inner wall of the container.

The guide may include a guide material. The guide material may include polymeric material. The guide material may include thermoplastic polymer. The guide material may include delrin. The guide material may include polypropylene. The guide material may include nylon. The guide material may include teflon. The guide material may include acrylonitrile butadiene styrene (ABS). The guide material may include polycarbonate. The guide material may include polysulfone. The guide material may include acrylic polymer. The guide material may include polymethylmethacrylate (PMMA). The guide material may include a stiff material. The guide material may include a material with a hardness more than about <NUM> Shore A durometer. The guide material may include a material with a low coefficient of friction. The guide material may include a material with a coefficient of friction of about <NUM> to about <NUM>.

The rod may include a rod material. The rod material may include polymeric material. The rod material may include thermoplastic polymer. The rod material may include delrin. The rod material may include polypropylene. The rod material may include nylon. The rod material may include teflon. The rod material may include ABS. The rod material may include polycarbonate. The rod material may include polysulfone. The rod material may include acrylic polymer. The rod material may include PMMA. The rod material may include a stiff material. The rod material may include a material with a hardness more than about <NUM> Shore A durometer. The rod material may include a material with a low coefficient of friction. The rod material may include a material with a coefficient of friction of about <NUM> to about <NUM>.

The housing may include a housing material. The housing material may include polymeric material. The housing material may include thermoplastic polymer. The housing material may include delrin. The housing material may include polypropylene. The housing material may include nylon. The housing material may include teflon. The housing material may include ABS. The housing material may include polycarbonate. The housing material may include polysulfone. The housing material may include acrylic polymer. The housing material may include PMMA. The housing material may include a stiff material. The housing material may include a material with a hardness more than about <NUM> Shore A durometer. The housing material may include a material with a low coefficient of friction. The housing material may include a material with a coefficient of friction of about <NUM> to about <NUM>. The housing material may include a material that is translucent. The housing material may include a material that is transparent.

The container may include a container material. The container material may include polymeric material. The plunger material may include amorphous material. The container material may include thermoplastic polymer. The container material may include glass. The container material may include type <NUM> borosilicate glass. The container material may include cyclic olefin copolymer (COC). The container material may include polypropylene. The container material may include PMMA. The container material may include a material that is translucent. The container material may include a material that is transparent.

The container material may include a container lubricious coating. The container lubricious coating may coat the container material. The container material may bear the container lubricious material. The container lubricious coating may include silicone oil. The container lubricious material may facilitate movement of the plunger or plungers within the container.

For example, some embodiments may feature an ABS plunger rod disposed in a passageway of a delrin guide affixed to a PMMA housing. The embodiments may feature, in a borosilicate glass container, silicone rubber plungers with PTFE coatings and a butyl rubber stopper with an ETFE coating. The embodiments may feature ABS trigger protrusions integral to the ABS rod, the protrusions supported by parallel helicoidal tracts of parallel helix-containing tracks of the mixing configuration. The embodiments may feature ABS end-walls of parallel longitudinal tracts of the helix-containing tracks, the end-walls serving as terminal surfaces of the helix-containing tracks. The embodiments may feature delrin bosses integral to the delrin guide, the delrin bosses of truncated pyramidal shape and oriented within the guide in conformity with a helical pitch of the helicoidal tracts of the tracks. Some embodiments may feature any other suitable combination of materials and/or geometries.

The device may include determination of the extent of the delivery stroke by abutment of the rod material with the guide material, the guide material fixed in place axially and rotationally relative to the housing. The greater hardness of rod material, guide material and housing material compared to the plunger material and the stopper material, may provide a greater reliability of low volume delivery through abutment of the boss against the terminal surface than provided by bottoming out a typical syringe plunger against a distal inner end of a typical syringe.

The device includes a collar. The collar may include any suitable material, including that referred to above in connection with the guide. The collar is disposed coaxial with the longitudinal axis. The collar includes a projection. The device includes the plunger rod. The plunger rod is threadingly engaged, coaxially within the collar, with the proximal knob. The proximal knob includes a track. The track may include an annular tract. The track may include a longitudinal tract. The boss may slidingly engage the annular tract to longitudinally retain the knob during a rotation of the knob about the axis. The boss may slidingly engage the longitudinal tract during a longitudinal translation of the knob. The projection slidingly engages a longitudinally extending structure of the rod to rotationally retain the rod during the rotation. The rotation may drive the rod toward the distal end.

The translation may be delimited by interference between the boss and a proximal terminal surface of the longitudinal tract. The translation may advance the target amount out of the distal end.

The longitudinal tract may intersect the annular tract. The rotation may be delimited by abutment of the boss against a lateral surface of the longitudinal tract. The longitudinal tract may retain the knob rotationally during the translation and may corresponds, in longitudinal extent, from the location of the abutment, to the target amount. The interference may limit motion of the boss, relative to the knob, to motion that is directed away from the terminal surface and parallel to the axis. The interference may terminate advancement of medicament out of the distal end.

The collar may include a bracket configured to retain, coaxially with the knob, a medicament container. The container may define a bore bound by an interior sidewall that defines, along a segment of the sidewall, a uniform diameter. A distal end of the rod may abut a plunger within the container. The plunger may be slidingly engaged with the sidewall.

Before the translation, the plunger may seal a pre-delivery amount of the medicament between an inner distal end-wall of the container and the plunger. After the translation, a distal portion of the segment may contact a bulk liquid residuum contained between the inner distal end-wall and the plunger. The amount of the medicament in the residuum may be an amount that is no greater than the pre-delivery amount less the target amount.

The rotation may set the pre-delivery amount. The rotation may prepare the medicament for delivery. The preparation may include mixing components of the medicament within the container.

The plunger may be the first plunger and, distal to the first plunger, the second plunger may slidingly engage with the segment.

Prior to the mixing, a liquid component of the medicament may be sealed within the container between the first plunger and the second plunger. The mixing may include transfer of the liquid component, within the container, distally past the second plunger. After the mixing, the distal face of the first plunger may abut the proximal face of the second plunger.

The preparing may include priming the container.

The priming may include the distal discharge of air from the container.

The knob may include signage. The signage may provide an indication of a stage of device operation. The collar may define a window. The window may expose a portion of the signage. The portion may indicate, prior to the rotation, a medicament preparation stage of the device operation. The portion may indicate, during the rotation, continuation of the preparation stage. The portion may indicate, after the rotation, a medicament delivery stage of the device operation.

The portion may indicate, after the rotation and prior to the translation, commencement of the delivery stage. The portion may indicate, after the translation, completion of the delivery stage.

The abutment may provide tactile indication of completion of a medicament preparation stage of device operation. The abutment may provide acoustic indication of completion of a medicament preparation stage of device operation.

The interference may provide an indication of completion of a medicament delivery stage of device operation.

The longitudinally extending structure may extend along a length of the rod that is disposed between a proximal thread of the rod and a distal end of the rod.

The longitudinally extending structure may support a surface feature configured to interfere with the projection to longitudinally retain the rod from proximal movement.

The surface feature may have a proximal stop surface. The proximal stop surface may provide blockage against distal movement of the projection relative to the surface feature. Distal to the stop surface, the surface feature may provide passage for proximal movement of the projection relative to the surface feature.

The projection projects radially inward. The projection may have a distal stop surface. The distal stop surface may provide blockage against distal movement of the projection relative to the surface feature. Proximal to the stop surface, the projection may provide passage for proximal movement of the projection relative to the surface feature.

The longitudinally extending structure may include a slot. The slot may extend radially inward. The surface feature may extend, in a plane transverse to the axis, into the slot.

The longitudinally extending structure may include a rail. The rail may extend radially outward. The surface feature may extend, in a plane transverse to the axis, radially outward from the rail.

The boss may include a flexible panel. The flexible panel may include a free end. The free end may be disposed more radially inward than any other surface of the boss. The free end may be disposed more radially inward than any other part of the boss.

A running surface of the track may support a trigger. The free end may be configured to, responsive to interaction between the free end and the trigger, deflect relative to the axis when the panel passes by the trigger.

The trigger may have a stop surface. The stop surface may be disposed on a plane transverse to the axis. The stop surface may be configured to block passage of the free end in a direction opposite to the rotation.

The trigger may include the protrusion. The interaction may involve an interference between the free end and the trigger. During the rotation, the panel may pass by the stop surface after passing by all other surfaces of the trigger.

The trigger may include a recess. The interaction may include an urging of the free end against the recess. During the rotation, the panel may pass by the stop surface before passing by any other surface of the trigger.

The interaction may occur upon initiation of the rotation.

Prior to the interaction, the boss may be disposed adjacent a portion of the annular tract that is circumferentially most distant, in the direction of the rotation, from the longitudinal tract. Prior to the interaction, the trigger may limit motion of the free end along the track.

The interaction may occur upon completion of the rotation.

The trigger may be disposed on the annular tract at a juncture of the annular tract and the longitudinal tract. The trigger, following the interaction, may limit rotary motion of the knob in a direction opposite the rotation.

The deflection may provide an indication of the interaction. The indication may be tactile. The indication may be acoustic.

The device includes the collar. The collar is disposed coaxial with the axis. The collar supports a flexible panel and a projection. The device includes the plunger rod. The plunger rod is threadingly engaged, coaxially within the collar, with the proximal knob. The proximal knob includes the track that supports the trigger.

The panel is configured to deflect, responsive to interaction with the trigger, relative to the axis. The panel slidingly engages the track to longitudinally retain the knob during a rotation of the knob about the axis. The rod includes a longitudinally extending structure. The projection slidingly engages the longitudinally extending structure to rotationally retain the rod during the rotation. The rotation drives the rod toward the distal end.

The track may include the annular tract. The track may include the longitudinal tract. The annular tract may intersect the longitudinal tract. The panel may slidingly engage the annular tract during the rotation. The panel may slidingly engage the longitudinal tract during a longitudinal translation of the knob. The longitudinal tract may retain the knob rotationally during the translation and may correspond, in longitudinal extent, from the intersecting, to the target amount. The translation may be delimited by interference between the panel and the proximal terminal surface of the longitudinal tract. The interference may limit motion of the panel, relative to the knob, to motion that is directed away from the terminal surface and parallel to the axis. The interference may terminate advancement of medicament out of the distal end.

The collar may support the bracket. The bracket may be configured to retain, coaxially with the knob, the medicament container. The container may define a bore bound by an interior sidewall that defines, along a segment of the sidewall, a uniform diameter. The distal end of the rod may abut the plunger within the container. The plunger may be slidingly engaged with the sidewall. Before the translation, the plunger may seal the pre-delivery amount of the medicament between the inner distal end-wall of the container and the plunger. After the translation, the distal portion of the segment may contact the bulk liquid residuum contained between the inner distal end-wall and the plunger.

The amount of the medicament in the residuum may be an amount that is no greater than the pre-delivery amount less the target amount. The distal portion of the segment may directly contact the residuum.

The rotation may set the pre-delivery amount. The rotation may prepare the medicament for delivery.

The priming may include distal discharge of air from the container. The priming may include distal discharge of an inert gas from the container.

The knob may include the signage. The signage may provide the indication. The indication may be an indication of a stage of device operation. The collar may define the window. The window may expose the portion of the signage. The portion may indicate, prior to the rotation, the medicament preparation stage of the device operation. The portion may indicate, after the rotation, the medicament delivery stage of the device operation.

The portion may indicate, during the rotation, continuation of the preparation stage.

The longitudinally extending structure may extend along a length that is disposed between a proximal thread of the rod and a distal end of the rod. The longitudinally extending structure may support the surface feature configured to interfere with the projection to longitudinally retain the rod from proximal movement.

The surface feature may include a proximal stop surface. The proximal stop surface may provide blockage against distal movement of the projection relative to the surface feature. Distal to the stop surface, the surface feature may provide passage for proximal movement of the projection relative to the surface feature.

The projection may project radially inward. The projection may include the distal stop surface. The distal stop surface may provide blockage against distal movement of the projection relative to the surface feature. Proximal to the stop surface, the projection may provide passage for proximal movement of the projection relative to the surface feature.

The longitudinally extending structure may include the slot that extends radially inward. The surface feature may extend, in the plane transverse to the axis, into the slot.

The longitudinally extending structure may include the rail that extends radially outward. The surface feature may extend, in the plane transverse to the axis, out from the rail.

The panel may be supported by the boss that is supported by the collar. In the rotation, the boss may be in sliding engagement with the annular tract. In the rotation, the panel may trail all other surfaces of the boss. In the rotation, the panel may trail all other parts of the boss. The panel may include the free end. The free end may be disposed more radially inward than any other surface of the panel. The free end may be disposed more radially inward than any other part of the panel.

In the rotation, the free end may trail all other surfaces of the panel. In the rotation, the free end may trail all other parts of the panel.

The running surface of the track may support the trigger. The free end may interact with the trigger to produce the deflection when the panel passes by the trigger.

The trigger may include the stop surface. The stop surface may be disposed on the plane transverse to the axis. The stop surface may be configured to block passage of the free end in a direction opposite to the rotation.

The trigger may include the protrusion. The interaction may be an interference between the free end and the trigger. During the rotation, the panel may pass by the stop surface after passing by all other surfaces of the trigger. During the rotation, the panel may pass by the stop surface after passing by all other parts of the trigger.

The trigger may include a recess. The interaction may include urging the free end against the recess. During the rotation, the panel may pass by the stop surface before passing by any other surface of the trigger. During the rotation, the panel may pass by the stop surface before passing by any other part of the trigger.

The interaction may occur upon initiation of the rotation. Prior to the interaction, the boss may be disposed adjacent a portion of the annular tract that is circumferentially most distant, in the direction of the rotation, from the longitudinal tract. Prior to the interaction, the trigger may limit motion of the free end along the track.

The trigger may be disposed on the annular tract at a juncture of the annular tract and the longitudinal tract. Following the interaction, the trigger may limit rotary motion of the knob in a direction opposite the rotation.

Following the interaction, the panel may be circumferentially aligned with the longitudinal tract.

The deflection may provide the indication of the interaction. The indication may be tactile. The indication may be acoustic.

The longitudinal tract may include a lateral surface. The rotation may be delimited by abutment of the boss against the lateral surface. The abutment may circumferentially align the boss with the longitudinal tract.

The abutment may provide tactile indication of completion of the medicament preparation stage of device operation. The abutment may provide acoustic indication of completion of the medicament preparation stage of device operation.

The interference may provide indication of completion of the medicament delivery stage of device operation.

The method is a method of manufacturing a medicament delivery device. The method includes providing the knob having the annular recess that includes the surface from which extends the protrusion. The method includes providing the collar that supports the flexible panel that extends into an interior of the collar. The method includes positioning the knob coaxially within the collar so that a free end of the panel extends radially inward beyond the protrusion and is deflectable by the protrusion when the knob rotates relative to the collar. The method includes threadingly engaging the plunger rod with the knob. The method includes securing the rod against rotation relative to the knob.

The providing a knob may include providing a knob that has a longitudinal recess. The longitudinal recess may intersect the annular recess. The longitudinal recess may support the terminal surface configured to abut the panel.

The providing a collar may include providing a collar that includes the projection. The securing may include engaging the projection with the longitudinally extending structure of the rod.

The longitudinally extending structure may include the slot. The engaging may include insertion of the projection into the slot.

The longitudinally extending structure may include the rail. The engaging may include positioning the projection alongside the rail.

The methods may include providing a rod that includes an end supporting a thread that is engageable with the knob.

The device includes the collar disposed coaxial with the axis. The collar includes the projection and the track. The track may include an annular tract and a longitudinal tract. The device includes the plunger rod. The plunger rod is threadingly engaged, coaxially within the collar, with the proximal knob. The proximal knob may include the boss.

The boss may slidingly engage the annular tract to longitudinally retain the knob during a rotation of the knob about the axis. The boss may slidingly engage the longitudinal tract during a longitudinal translation of the knob. The projection may slidingly engage the longitudinally extending structure of the rod to rotationally retain the rod during the rotation. The rotation may drive the rod toward the distal end. The translation may be delimited by interference between the boss and the proximal terminal surface of the longitudinal tract. The translation may advance the target amount out of the distal end.

The longitudinal tract may intersect the annular tract. The rotation may be delimited by abutment of the boss against the lateral surface of the longitudinal tract. The abutment may circumferentially align the boss with the longitudinal tract. The longitudinal tract may retain the knob rotationally during the translation and corresponds in longitudinal extent, from a location of the abutment, to the target amount.

The interference may limit motion of the boss, relative to the collar, to motion that is directed away from the terminal surface and parallel to the axis. The interference may terminate advancement of medicament out of the distal end.

The collar may include the bracket. The bracket may be configured to retain, coaxially with the knob, a medicament container. The container may define a bore bound by an interior sidewall that defines, along a segment of the sidewall, a uniform diameter. The distal end of the rod may abut a plunger within the container. The plunger may be slidingly engaged with the sidewall.

Before the translation, the plunger may seal a pre-delivery amount of the medicament between the inner distal end-wall of the container and the plunger. After the translation, a distal portion of the segment may contact the bulk liquid residuum contained between the inner distal end-wall and the plunger. The amount of the medicament in the residuum may be an amount that is no greater than the pre-delivery amount less the target amount.

The rotation may set the pre-delivery amount. The rotation may prepare the medicament for delivery. The preparing may include mixing components of the medicament within the container.

The preparing may include priming the container. The priming may include distal discharge of air from the container. The priming may include distal discharge of inert gas from the container.

The knob may include signage that provides an indication of the stage of device operation. The collar may define the window exposing the portion of the signage. The portion may indicate, prior to the rotation, a medicament preparation stage of the device. The portion may indicate, after the rotation, a delivery stage of the device. The portion may indicate, during the rotation, continuation of the medicament preparation stage.

The abutment may provide tactile indication of completion of the medicament preparation stage. The abutment may provide acoustic indication of completion of the medicament preparation stage. The interference may provide the indication of completion of the medicament delivery stage of device operation.

The longitudinally extending structure may include the slot that extends along a length that is disposed between the proximal thread of the rod and the distal end of the rod. The longitudinally extending structure may include a rail that extends along a length that is disposed between the proximal thread of the rod and the distal end of the rod.

The device will be described now with reference to the accompanying drawings in the figures, which form a part hereof. It is to be understood that other embodiments may be utilized and that structural, functional and procedural modifications may be made without departing from the scope of protection provided by the claims.

<FIG> shows illustrative medicament delivery device <NUM>.

Delivery device <NUM> defines longitudinal axis L. Delivery device <NUM> is shown in a state that is a pre-operational state. In use of delivery device <NUM>, the pre-operational state precedes an operational state. In the pre-operational state, delivery device <NUM> is fully assembled. In the pre-operational state, delivery device <NUM> may be prepared for priming. In the pre-operational state, delivery device <NUM> may be prepared for preparation of medicament for discharge. In the pre-operational state, delivery device <NUM> may be prepared for discharge of medicament. In the pre-operational state, discharge of medicament from delivery device <NUM> has not begun.

Delivery device <NUM> includes proximal knob <NUM>. Knob <NUM> is disposed coaxial with axis L. Grip <NUM> may be provided on knob <NUM>.

Delivery device <NUM> includes plunger rod <NUM>. Rod <NUM> may be a component of a mixing configuration (not shown). Knob <NUM> is threadingly attached to rod <NUM>.

Delivery device <NUM> may include medicament container <NUM>. Container <NUM> may be a component of a mixing configuration (not shown). Container <NUM> may be disposed coaxial with axis L. Container <NUM> may be cylindrical, partially cylindrical or have any other suitable form. A distal portion of rod <NUM> may be disposed within container <NUM>.

Container <NUM> may contain medicament component <NUM>. Container <NUM> may be engaged with plunger <NUM>. A distal end of rod <NUM> may abut a proximal surface of plunger <NUM>.

Delivery device <NUM> may include device housing <NUM>. Housing <NUM> may be disposed coaxial with axis L. Housing <NUM> may be cylindrical, partially cylindrical or have any other suitable form.

Delivery device <NUM> may include finger flange <NUM>. Finger flange <NUM> may be separate from housing <NUM>. Finger flange <NUM> may be attached to housing <NUM>. Finger flange <NUM> may be integral to housing <NUM>.

Delivery device <NUM> includes collar <NUM>. Collar <NUM> is disposed coaxial with axis L. Collar <NUM> may be cylindrical, partially cylindrical or have any other suitable form. Collar <NUM> may be attached to finger flange <NUM>. Collar <NUM> may be integral to finger flange <NUM>. Collar <NUM> may be attached to housing <NUM>. Collar <NUM> may be integral to housing <NUM>.

<FIG> shows features of delivery device <NUM>. <FIG> shows knob <NUM>. Knob <NUM> contains threads <NUM> (shown in phantom) internal to knob <NUM>.

Grip <NUM> may contribute to traction on knob <NUM> for effecting longitudinal translation of rod <NUM>. Grip <NUM> may contribute to ergonomic finger contact of the operator with knob <NUM> for effecting longitudinal translation of rod <NUM>. The finger contact with knob <NUM> through grip <NUM> may conduct tactile feedback to the operator of an extent of distal longitudinal translation of rod <NUM> along axis L.

Knob <NUM> may include turn ridges <NUM>. Turn ridges <NUM> may be utilized by the operator to effect rotation of knob <NUM> about axis L. Turn ridges <NUM> may contribute to traction on knob <NUM> for effecting translation of rod <NUM>. Turn ridges <NUM> may contribute to ergonomic finger contact of the operator with knob <NUM> for effecting translation of rod <NUM> through rotation of knob <NUM>. The finger contact with turn ridges <NUM> may conduct tactile feedback to the operator of an extent of translation of rod <NUM> along axis L.

Turn ridges <NUM> may be spaced circumferentially around knob <NUM>. Turn ridges <NUM> may be spaced regularly around a circumference of grip <NUM>. Turn ridges <NUM> being spaced regularly about the circumference of grip <NUM> may provide the operator a measure of an extent of rotation performed.

Knob <NUM> may include turn direction signage <NUM>. In the operational state, delivery device <NUM> may effect distal displacement of rod <NUM> within container <NUM> in response to rotation of knob <NUM> about axis L in only one of two rotational directions. Turn direction signage <NUM> may provide the operator with cues as to an effective rotational direction. The cues may serve as reminders before and/or during the operational state. The cues may be visual. The cues may be tactile.

As depicted, the effective rotational direction for distal displacement of rod <NUM> within container <NUM> in response to rotation of knob <NUM> about axis L may be clockwise for delivery device <NUM>. (For some embodiments, not shown, counter-clockwise rotation may the effective rotational direction. For some embodiments, turn direction signage may provide cues for counter-clockwise rotation.

Distal rod end <NUM> may define a distal end of anti-rotation slot <NUM>. Anti-rotation slot <NUM> may be parallel to axis L. Distal rod end <NUM> may include one or more additional anti-rotation slots or features (not shown) distributed about the circumference of rod <NUM> in a regular or irregular manner. Anti-rotation slot <NUM> may extend all or some of the way proximally to threads <NUM>. Threads <NUM> extend proximally some or all of the way to proximal rod end <NUM>. Threads <NUM> engage threads <NUM> of knob <NUM>.

Rod <NUM> may include flat face <NUM>. Flat face <NUM> may be parallel to axis L. Rod <NUM> may include one or more additional flat faces (not shown) distributed about the circumference of rod <NUM> in a regular or irregular manner. Flat face <NUM> may extend all or some of the way from near anti-rotation slot <NUM> to proximal end <NUM>. Flat face <NUM> may be longitudinally coextensive with threads <NUM>. Flat face <NUM> may be circumferentially displaced from slot <NUM>. The circumferential displacement may be <NUM>° of arc from slot <NUM>.

Container <NUM> may be disposed in device <NUM> distal to finger flange <NUM>. Container <NUM> may be disposed in housing <NUM> distal to finger flange <NUM>. Proximal rim <NUM> of container <NUM> surrounding a proximal opening of container <NUM> may be recessed in device <NUM> distal to finger flange <NUM>. Proximal rim <NUM> of container <NUM> may be recessed in housing <NUM>.

Knob <NUM> is disposed coaxially within collar <NUM>. Collar <NUM> may include viewing window <NUM>. A portion of signage <NUM> may be visible through window <NUM>.

Rod <NUM> may be contained in container <NUM> with distal end <NUM> abutting plunger proximal face <NUM>. Proximal rod end <NUM> extends proximally into collar <NUM>. Knob <NUM> extends distally into collar <NUM> to threadingly engage rod <NUM>.

<FIG> shows collar <NUM>. Collar <NUM> may include boss <NUM>. Collar <NUM> includes flexible panel <NUM>. Flexible panel <NUM> may be included in boss <NUM>. Boss <NUM> may be disposed on an interior portion of collar <NUM>. Flexible panel <NUM> is disposed on an interior portion of collar <NUM>.

Knob <NUM> includes operational track <NUM>. Operational track <NUM> may begin at lateral surface <NUM>. Adjacent lateral face <NUM>, track <NUM> includes protrusion <NUM>. Boss <NUM> may slidingly engage track <NUM>. Flexible panel <NUM> interacts with protrusion <NUM>.

<FIG> is a cross-sectional view taken along viewlines <NUM>-<NUM> (shown in <FIG> shows track <NUM> and lateral surface <NUM> disposed on a periphery of knob <NUM>. Track <NUM> may include annular tract <NUM>. Annular tract <NUM> may support protrusion <NUM>. Annular tract <NUM> may support protrusion <NUM>. Track <NUM> may include longitudinal tract <NUM>. Track <NUM> may include running surface <NUM>.

<FIG> shows knob <NUM> extending into collar <NUM> such that flexible panel <NUM> of collar <NUM> is adjacent protrusion <NUM> of knob <NUM>.

<FIG> is a cross-sectional view taken along view lines <NUM>-<NUM> (shown in <FIG>). <FIG> shows collar <NUM>, boss <NUM> and flexible panel <NUM>.

<FIG> shows a view of collar <NUM> that is different from the view shown in <FIG> shows boss <NUM> and flexible panel <NUM>. Flexible panel <NUM> may include free end <NUM>. Opening O in collar <NUM> may be adjacent to flexible panel <NUM>.

<FIG> shows delivery device <NUM> assembled in a pre-operational state. Knob <NUM> extends into collar <NUM>. Flexible panel <NUM> may be adjacent to protrusion <NUM>. X shows the distance away from interior knob surface <NUM> of proximal rod end <NUM>. Proximal rod end <NUM> may be at a position x<NUM> from interior surface <NUM>. Rod <NUM> may abut plunger <NUM> within container <NUM>. Distal plunger face <NUM> may seal medicament <NUM> within container <NUM>. Y shows the distance away from container inflection point <NUM> of distal plunger face <NUM>. Distal face <NUM> may be disposed at a distance y<NUM> from inflection point <NUM> near a distal end of container <NUM>. Inflection point <NUM> is at a distal termination of a constant diameter of container <NUM> and illustrates an arbitrary reference point along an inner sidewall of container <NUM> to show how medicament discharge is proportional to movement of other elements of the device. Distal to inflection point <NUM>, the sidewall of container <NUM> may include shoulder <NUM>. Window <NUM>, shown in detail in inset, proximal to finger flange <NUM> reveals signage <NUM>.

<FIG> is a cross-sectional view taken along view lines <NUM>-<NUM> (shown in <FIG>) and rotated about <NUM>° from the view shown in <FIG> shows signage <NUM> through window <NUM>. The cross-section through finger flange <NUM> shows rod <NUM> and slot <NUM>. Anti-rotation projection <NUM> extends into anti-rotation slot <NUM>. A corresponding anti-rotation slot and anti-rotation projection (shown, but not numbered) may be present on the opposite side of rod <NUM>. Engagement of one or more of the projections in one or more of the slots operationally prevent rotation of rod <NUM>.

<FIG> is a cross-sectional view taken along view lines <NUM>-<NUM> (shown in <FIG> shows rod <NUM> concentric within knob <NUM>. Knob <NUM> is within and concentric to collar <NUM>. Boss <NUM> is shown with an inner radial surface disposed alongside annular tract <NUM>. Protrusion <NUM> lies between free end <NUM> of flexible panel <NUM> and the rest of boss <NUM>. Arrow A indicates rotation of knob <NUM> that may shift longitudinal tract <NUM> alongside boss <NUM>.

Angle Φ gives the rotational displacement between knob <NUM> and collar <NUM>. In the pre-operational state of rotation, Φ is φ<NUM>. Rotation of knob <NUM> in the direction of arrow A may bring free end <NUM> of panel <NUM> into interaction with protrusion <NUM>. The interaction causes a deflection of free end <NUM>. The interaction causes a deflection of panel <NUM>. The interaction may produce a sensible indication. The indication may be tactile, acoustic or both. Opening O (shown in <FIG>) may contribute to sensibility of acoustic indication.

With rotation of rod <NUM> prevented by interaction of rod <NUM> and projection <NUM> (shown in <FIG>) and with knob <NUM> being threadingly engaged with rod <NUM>, rotation of knob <NUM> displaces rod <NUM> axially.

After free end <NUM> passes over protrusion <NUM> in direction A, protrusion <NUM> interferes with free end <NUM>, thus preventing back-rotation of knob <NUM>.

<FIG> shows device <NUM> in a state different from that shown in <FIG>. Knob <NUM> is shown rotated relative to its position vis-à-vis collar <NUM> as shown in <FIG>. (The rotational position of knob <NUM> in <FIG> corresponds to the rotational position of knob <NUM> in <FIG>. The rotational position of knob <NUM> in <FIG> corresponds to the rotational position of knob <NUM> in <FIG>.

<FIG> shows knob <NUM> by itself in the same orientation in which it is shown in <FIG> shows annular tract <NUM> and longitudinal tract <NUM> of track <NUM>. Running surface <NUM> is visible. Longitudinal tract <NUM> of track <NUM> is visible. Annular tract <NUM> is visible.

<FIG> shows free end <NUM> of flexible panel <NUM> alongside running surface <NUM>. The rotation of knob <NUM> is illustrated to have caused a longitudinal translation of rod <NUM>. Proximal rod end <NUM> has been shifted longitudinally from position x<NUM> (shown in <FIG>) to position x<NUM>. The distal shift of rod <NUM> within container <NUM> has distally displaced plunger <NUM> so that distal face <NUM> is disposed at position y<NUM>, thus driving medicament <NUM> out of the distal end of the device. The medicament may be driven out in proportion to the rotation of knob <NUM> within collar <NUM>. Signage <NUM> may indicate through window <NUM> that the rotation has begun to occur.

<FIG> is a cross-sectional view taken along view lines <NUM>-<NUM> (shown in <FIG> shows knob <NUM> rotated relative to collar <NUM> to angle φ<NUM>. Further rotation in Φ may bring boss <NUM> into longitudinal tract <NUM>.

<FIG> shows delivery device <NUM> in a state different from that shown in <FIG>. The state shown in <FIG> may correspond to termination of rotation of knob <NUM> within collar <NUM>.

<FIG> shows knob <NUM> by itself in the same orientation in which it is shown in <FIG> shows annular tract <NUM> intersecting longitudinal tact <NUM>. Projection <NUM> may be contiguous or near contiguous with intersection of annular tract <NUM> and longitudinal tact <NUM>.

<FIG> shows free end <NUM> of flexible panel <NUM> alongside protrusion <NUM>. The rotation of knob <NUM> is illustrated to have caused a longitudinal translation of rod <NUM>. Proximal rod end <NUM> has been shifted longitudinally to position x<NUM>. The distal shift of rod <NUM> within container <NUM> has distally displaced plunger <NUM> so that distal face <NUM> is disposed at position y<NUM> relative to inflection point <NUM>, thus driving medicament <NUM> out of the distal end of the device. The medicament may be driven out in proportion to the rotation of knob <NUM> within collar <NUM>. Signage <NUM> may indicate through window <NUM> that the rotation has terminated and the device is ready for medicament delivery by longitudinal distal displacement of knob <NUM> relative to collar <NUM>.

<FIG> is a cross-sectional view taken along view lines <NUM>-<NUM> (shown in <FIG> shows knob <NUM> rotated relative to collar <NUM> to angle φ<NUM>. The rotation now has brought boss <NUM> into longitudinal tract <NUM>. The rotation has brought free end <NUM> into interaction with protrusion <NUM> as panel <NUM> passed over protrusion <NUM>. The interaction causes a deflection of free end <NUM>. The interaction causes a deflection of panel <NUM>. The interaction may produce a sensible indication. The indication may be tactile, acoustic or both. After free end <NUM> passes over protrusion <NUM> and enters longitudinal tract <NUM>, protrusion <NUM> interferes with free end <NUM>, thus preventing back-rotation of knob <NUM>. Lateral surface <NUM> interferes with boss <NUM>, thus preventing further rotation of knob <NUM>. Boss <NUM> is now confined to longitudinal tract <NUM> and the device is prepared for delivery of medicament as a result of distal longitudinal displacement of knob <NUM> relative to collar <NUM>.

<FIG> shows device <NUM> inverted to illustrate a medicament delivery orientation. Longitudinal tract <NUM> includes terminal surface <NUM> (shown in break-away view). Z gives the distance of boss <NUM> from terminal surface <NUM>. In the view shown, Z is z<NUM>. When Z is z<NUM>, device <NUM> is ready for, but has not yet begun, delivery of medicament <NUM>. When knob <NUM> is displaced longitudinally along direction B into collar <NUM>, medicament <NUM> is discharged.

<FIG> shows device <NUM> upon completion of medicament delivery. Longitudinal displacement of knob <NUM> relative to collar <NUM> brings boss <NUM> into abutment with terminal surface <NUM>, thus terminating longitudinal displacement of rod <NUM> and plunger <NUM>. Z is now z<NUM>, which is about zero. Distal face <NUM> is displaced to y<NUM>. The distance between y<NUM> and y<NUM> is proportional, through the diameter of the container, to the target amount. Position y<NUM> may be proximal to inflection point <NUM>. Position y<NUM> may be longitudinally even with inflection point <NUM>. When distal face <NUM> is at y<NUM>, a residuum of medicament <NUM> may remain between distal face <NUM> and the distal end of container <NUM>. When distal face <NUM> is at y<NUM>, a residuum of medicament <NUM> may remain between distal face <NUM> and shoulder <NUM>. The residuum may be a bulk liquid. The bulk liquid may have a volume that is greater than the volume of a film or a drop that would be expected to adhere to container <NUM>.

Distal face <NUM> is thus detained prior to crossing inflection point <NUM>. This may avoid deformation of distal face <NUM> against shoulder <NUM>. The deformation may cause a discrepancy between the target amount and the actual amount discharged through the distal end of device <NUM>.

Claim 1:
A medicament delivery device (<NUM>) defining a longitudinal axis and having a distal end, the device comprising:
a proximal knob (<NUM>);
a plunger rod (<NUM>) having a longitudinally extending structure (<NUM>);
a collar (<NUM>) disposed coaxial with the longitudinal axis,
the collar including:
an anti-rotation projection (<NUM>) extending radially inwardly into the interior of the collar (<NUM>), the anti-rotation projection (<NUM>) being configured to slidingly engage the longitudinally extending structure (<NUM>) of the rod (<NUM>);
characterized in that the anti-rotation projection (<NUM>) is further configured to rotationally retain the rod (<NUM>) during a rotation of the knob (<NUM>) about the longitudinal axis, the rotation thereby driving the rod (<NUM>) toward the distal end;
in that the plunger rod (<NUM>) is threadingly engaged, coaxially within the collar (<NUM>), with the proximal knob (<NUM>), the proximal knob (<NUM>) being coaxially disposed within the collar (<NUM>) and having a track (<NUM>) that includes a protrusion (<NUM>, <NUM>);
and in that the collar (<NUM>) includes a flexible panel (<NUM>) disposed on an interior portion of the collar (<NUM>) and extending into the interior of the collar (<NUM>), wherein:
the panel (<NUM>) is configured to:
move in deflection relative to the axis, responsive to interaction with the protrusion (<NUM>, <NUM>); and
slidingly engage the track (<NUM>) to longitudinally retain the knob (<NUM>) during the rotation of the knob (<NUM>) about the longitudinal axis.