Patent Publication Number: US-11383042-B2

Title: Drive mechanisms suitable for use in drug delivery devices

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application is a continuation of U.S. patent application Ser. No. 16/254,087, filed Jan. 22, 2019, which is a continuation of U.S. patent application Ser. No. 15/352,893, filed Nov. 16, 2016, now U.S. Pat. No. 10,226,579, which is a continuation of U.S. patent application Ser. No. 14/504,016, filed Oct. 1, 2014, now U.S. Pat. No. 9,526,843, which is a continuation of U.S. patent application Ser. No. 13/667,449, filed Nov. 2, 2012, now U.S. Pat. No. 8,876,782, which is a continuation of U.S. patent application Ser. No. 13/280,903, filed Oct. 25, 2011, now U.S. Pat. No. 8,574,198, which is a continuation of U.S. patent application Ser. No. 12/453,626, filed May 15, 2009, now U.S. Pat. No. 8,070,727, which is a continuation of U.S. patent application Ser. No. 10/790,024, filed Mar. 2, 2004, now U.S. Pat. No. 7,553,299, which claims priority to GB Patent Application No. 0304823.8, filed Mar. 3, 2003. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
    
    
     THE TECHNICAL FIELD OF THE INVENTION 
     The present invention relates to drive mechanisms suitable for use in drug delivery devices, in particular pen-type injectors, having dosage setting means, enabling the administration of medicinal products from a multi-dose cartridge. In particular, the present invention relates to such drug delivery devices where a user may set the dose. 
     DESCRIPTION OF RELATED ART 
     Such drug delivery devices have application where regular injection by persons without formal medical training occurs, i.e., patients. This is increasingly common amongst those having diabetes where self-treatment enables such persons to conduct effective management of their diabetes. 
     These circumstances set a number of requirements for drug delivery devices of this kind. The device must be robust in construction, yet easy to use in terms of the manipulation of the parts, understanding by a user of its operation and the delivery of the required dose of medicament. Dose setting must be easy and unambiguous. In the case of those with diabetes, many users will be physically infirm and may also have Impaired vision requiring the drive mechanism to have low dispensing force and an easy to read dose setting display. Where the device is to be disposable rather than reusable, the device should be cheap to manufacture and easy to dispose of (preferably being suitable, for recycling). To meet these requirements the number of parts required to assemble the device and the number of material types the device is made from need to be kept to a minimum. 
     User operated drug delivery devices are well known within the medical field. 
     WO9938554A2 teaches an injection syringe for apportioning set doses of a medicine from a cartridge wherein a drive mechanism comprising a unidirectional coupling (i.e., a ratchet) is disclosed which allows correction of a set overdose without dispensing the set amount of fluid or requiring the dismantling of the cartridge. 
     EP0937471A2 discloses a medication delivery pen having a drive mechanism comprising a unidirectional coupling (i.e, a ratchet) located between the rod barrel tube and the housing. The disclosed drive mechanism is of the direct type, which means that relatively high actuation force is required by the user. 
     Surprisingly it was found that a drive mechanism comprising a unidirectional coupling and a clutch mechanism according to instant invention provides lower actuation forces for the user or, alternatively, allows application of greater volumes of medicinal products. Additionally the drive mechanism of instant invention provides the advantage of intuitive, safe, and easy to use correction of a set dose and it further provides improved protection of the working parts from dust and debris. 
     DESCRIPTION OF THE INVENTION 
     Therefore, a first object of instant invention is a drive mechanism for use in a drug delivery device comprising: 
     a housing having an internal and an external thread; 
     a piston rod having a non-circular cross section, and which is threadedly engaged with the internal thread of the housing; 
     a unidirectional coupling located between the housing and the piston rod; 
     a dose dial sleeve, which is threadedly engaged with the external thread of the housing and being rotatable with respect to the housing; 
     a drive sleeve, located between the housing and the piston rod, which is axially displaceable but not rotatable with respect to the piston rod; and 
     a clutch means located between the drive sleeve and the dose dial sleeve, which
         a. when the dose dial sleeve and the drive sleeve are de-coupled by the said clutch means, rotation of said dose dial sleeve with respect to said drive sleeve is allowed; and   b. when the dose dial sleeve and drive sleeve are coupled by the said clutch means rotation of the does dial sleeve with respect to the said drive sleeve is prevented.       

     The term “drug delivery device” according to instant invention shall mean a single-dose or multi-dose, disposable or re-useable device designed to dispense a selected dose of a medicinal product, preferably multiple selected doses, e.g. Insulin, growth hormones, low molecular weight heparins, and their analogues and/or derivatives etc. Said device may be of any shape, e.g. compact or pen-type. Dose delivery may be provided through a mechanical (optionally manual) or electrical drive mechanism or stored energy drive mechanism, such as a spring, etc. Dose selection may be provided through a manual mechanism or electronic mechanism. Additionally, said device may contain components designed to monitor physiological properties such as blood glucose levels, etc. Furthermore, the said device may comprise a needle or may be needle-free. In particular, preferred embodiment the term drug delivery device shall mean a disposable multi-dose pen-type device having mechanical and manual dose delivery and dose selection mechanisms, which is designed for regular use by persons without formal medical training such as patients. Preferably, the drug delivery device is of the injector-type. Optionally, the drug delivery device according to instant invention further comprises a nut threadedly connected to the drive sleeve and rotatable with respect to the drive sleeve and which is engaged with the dose dial sleeve to allow axial displacement of the nut with respect to the dose sleeve, but not rotation of the nut with respect to the dose dial sleeve. 
     The term “housing” according to instant invention shall preferably mean an exterior housing (“main housing”, “body, “shell”) or interior housing (“inner body”, “insert”) having an internal and an external thread. The housing may be designed to enable the safe, correct, and comfortable handling of the drug delivery device or any of its mechanisms. Usually, it is designed to house, fix, protect, guide, and/or engage with any of the inner components of the drug delivery device (e.g., the drive mechanism, cartridge, plunger, piston rod) by limiting the exposure to contaminants, such as liquid, dust, dirt etc. In general, the housing may be unitary or a multipart component of tubular or non-tubular shape. Usually, the exterior housing serves to house a cartridge from which a number of doses of a medicinal product may by dispensed. 
     In a more specific embodiment of instant invention, the interior housing is provided with a plurality of maximum dose stops adapted to be abutted by a radial stop provided on the dose dial sleeve. 
     In a more particular embodiment of instant invention, the interior housing comprises a web having an opening through which the piston may extend. A first cylindrical portion may extend from the first end of the web, and a second and a third cylindrical portion may extend from the second end of the web. Preferably, the second cylindrical portion is provided with an internal thread. 
     In a further embodiment of instant invention, the insert comprises a web having an opening through which the piston may extend. A first cylindrical portion may extend from a first end of the web, a boss provided on a second end of the web and a cylindrical portion extending away from the web about a periphery of the boss. 
     Optionally, the boss is provided with an internal thread or a radial flange being spaced from the web with a cylindrical portion extending away from the web about a periphery of the radial flange 
     The term “engaged” according to instant invention shall particularly mean the interlocking of two or more components of the drive mechanism/drug delivery device, e.g. a spline or thread connection, preferably the interlocking of helical threads of components (“threadedly engaged”). 
     The term “thread” according to instant invention shall preferably mean a full or part thread, e.g., a cylindrical spiral rib/groove, usually of helical nature, located on the internal and/or external surface of a component of the drug delivery device (“internal thread” and/or “external thread”), having an essentially triangular or square or rounded section designed to allow continuous free rotational and/or axial movement between components. Optionally, a thread may be further designed to prevent rotational or axial movement of certain components in one direction. 
     The term “dose dial sleeve” according to instant invention shall mean an essentially tubular component of essentially circular cross-section having either:
         a. a) both an internal and external thread, or   b. b) an internal thread, or   c. c) an external thread,
 
said dose dial sleeve may be made or constructed of one or more parts. Preferably, the “dose dial sleeve” according to instant invention comprises an internal helical thread, which is threadedly engaged with the external thread of the housing, particularly the insert.
       

     In yet another preferred embodiment the dose dial sleeve is designed to indicate a selected dose of a dispensable product. In still another preferred embodiment of instant invention, the maximum selectable dose may be determined by the abutment of a radially directed lug on the dose dial sleeve with a catch means on the insert following the maximum angular displacement of the dose dial sleeve with respect to the housing. Preferably, the radially directed lug extends parallel to a longitudinal axis of the dose dial sleeve. 
     Generally, the term “catch means” according to instant invention shall mean any constructive feature, which serves as a counterpart to the lug on the dose dial sleeve and which is preferably located on the outer surface of the insert, and which together with the lug of the dose dial sleeve defines the maximum allowable dosage of the mechanism. Optionally, the catch means may be a groove extending about a central land, e.g., a central land being wedge shaped such that a first edge extends radially less far than a second opposite edge to define a sloping surface between the first edge and the second edge. 
     Indication of the selected dose on the dose dial sleeve may be achieved by use of markings, symbols, numerals, etc., e.g., printed on the external surface of the dose dial sleeve or an odometer, or the like. 
     In a more specific embodiment of instant invention, the dose dial sleeve comprises a first section of a first diameter and a second section of second diameter. 
     The term “lead” according to instant invention shall preferably mean the axial distance a nut would advance in one complete revolution; preferably “lead” shall mean the axial distance through which a component having a helical thread, i.e., dose dial sleeve, piston rod, etc., of the drive mechanism travels during one rotation. Therefore lead is a function of the pitch of the thread of the relevant component. 
     The term “pitch” according to instant invention shall preferably mean the distance between consecutive contours of the helical thread, measured parallel to the axis of the helical thread. 
     The term “drive sleeve” according to instant invention shall mean any essentially tubular component of essentially circular cross-section and which is further located between the housing, preferably the internal housing and the piston rod, and which is axially displaceable but not rotatable with respect to the piston rod. The drive sleeve of the invention is further releasably connected to the dose dial sleeve by a clutch means and is further engaged with the piston rod at the distal and/or proximal end. The drive sleeve may further comprise a first section of the first diameter located between the insert and the piston rod and a second section of second diameter located between the piston rod and the dose dial sleeve. 
     The term “releasably connected” according to instant invention shall preferably mean that two components of instant mechanism or device are reversibly joined to each other, which allows coupling and decoupling, e.g., by means of a clutch. 
     The term “piston rod” according to instant invention shall mean a component adapted to operate through/within the housing, designed to translate axial movement through/within the drug delivery device, preferably from the drive sleeve to the piston, for the purpose of discharging/dispensing an injectable product. Said piston rod may be flexible or not. It may be a simple rod, a lead-screw, or the like. The “piston rod” according to instant invention shall further mean a component having a non-circular cross-section and an external thread located on its first end. It may be made of any suitable material known by a person skilled in the art. 
     The term “first end” according to instant invention shall mean the proximal end. The proximal end of the device or a component of the device shall mean the end, which is closest to the dispensing end of the device. 
     The term “second end” according to instant invention shall mean the distal end. The distal end of the device or a component of the device shall mean the end, which is furthest away from the dispensing end of the device. 
     The term “clutch means” according to instant invention shall mean any means, which releasably connects the dose dial sleeve and the drive sleeve and which is located between the drive sleeve and the dose dial sleeve, and which allows rotation of the dose dial sleeve with respect to said drive sleeve when the dose dial sleeve and the drive sleeve are de-coupled, and which prevents rotation of the dose dial sleeve with respect to the drive sleeve when the dose dial sleeve and drive sleeve are coupled. According to instant invention the term “clutch means” encompasses any clutch mechanism engaging for the purpose of reversibly locking two components in rotation, e.g., by use of axial forces to engage a set of face teeth (saw teeth, dog teeth, crown teeth) or any other suitable frictional faces. 
     In still another embodiment of instant invention, the drive mechanism further comprises a clicker means. Preferably, the “clicker means” shall mean any means located between the dose dial sleeve and the drive sleeve, which upon relative rotation of the said drive sleeve and the said dose dial sleeve causes a series of audible and/or tactile clicks. 
     Such a clicker means may comprise a plurality of longitudinally extending teeth and a flexible toothed member, one of the plurality of teeth and the toothed member being provided on the dose dial sleeve, the other being provided on the drive sleeve. 
     The term “unidirectional coupling” according to instant invention shall mean any mechanism located between the housing and the piston rod, which allows movement of the piston rod in the proximal direction and prevents movement of the piston rod in the distal direction, preferably acting between the non-circular cross section of the piston rod and the housing. 
     A second aspect of instant invention provides an assembly for use in a drug delivery device comprising the drive mechanism according to instant invention. 
     A third aspect of the present invention provides a drug delivery device comprising the drive mechanism or the assembly according to instant invention. 
     A fourth aspect of the present invention provides a method of assembling a drug delivery device comprising the step of providing a drive mechanism or an assembly according to instant invention. 
     A fifth aspect of instant invention is the use of a drug delivery device according to instant invention for dispensing a medicinal product, preferably dispensing a pharmaceutical formulation (e.g. solution, suspension etc.) comprising an active compound selected from the group consisting of insulin, growth hormone, low molecular weight heparin, their analogues and their derivatives. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Without any limitation, the instant invention will be explained in greater detail below in connection with a preferred embodiment and with reference to the drawings in which: 
         FIG. 1  shows a sectional view of a first embodiment of the drug delivery device, in accordance with the present invention in a first, cartridge full, position; 
         FIG. 2  shows a sectional view of the drug delivery device of  FIG. 1  in a second, maximum first dose dialed, position; 
         FIG. 3  shows a sectional view of the drug delivery device of  FIG. 1  in a third, maximum first dose dispensed, position; 
         FIG. 4  shows a sectional view of the drug delivery device of  FIG. 1  in a fourth, final dose dialed, position; 
         FIG. 5  shows a sectional view of the drug delivery device of  FIG. 1  in a fifth, final dose dispensed, position; 
         FIG. 6  allows a sectional view of a second embodiment of the drug delivery device in accordance with the prevent invention; 
         FIG. 7  shows a sectional side view of a third embodiment of the drug delivery device in accordance with the present invention; 
         FIG. 8  shows a perspective view of a dose dial sleeve for use in conjunction with the present invention; 
         FIG. 9  shows a perspective view of an insert for use with the dose dial sleeve of  FIG. 8 ; 
         FIG. 10  shows a sectional side view of a fourth embodiment of the drug delivery device in accordance with the present invention; and 
         FIG. 11  shows a sectional side view of a fifth embodiment of the drive mechanism according to instant invention in a first, cartridge full, position. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     Example 1 
     Referring to  FIGS. 1 to 5  there is seen a drug delivery device in accordance with the first embodiment of the present invention. The device comprises a housing  2  within which are located a cartridge  4  containing medicinal product, means for setting or selecting the dose of medicinal product to be expelled and means for expelling the selected dose of medicinal product. The housing  2  is generally cylindrical in shape and is divided into two compartments by a web  6  to be described in more detail below. The cartridge  4  is located within a first part of the housing  2 . The dose setting means and the means for expelling the selected dose of medicinal product are retained; that is held, within a second part of the housing  2 . An advantage of a one piece housing enclosing the cartridge  4  together with the dose setting and dose expelling means lies in the ease of assembly of the product. This is in part due to the reduced number of components in the pen-type injector. Also, the unitary nature of the housing  2  means that the pen-type injector is mode robust. 
     The cartridge  4  may be secured in position in the first part of the housing  2  by any suitable means. A needle unit may be secured to a first end of the cartridge  4 . A temporary covering  8  is shown in this position in the Figures. The cartridge  4  further comprises a displaceable piston  10 . Advancing the piston  10  towards the first end of the cartridge  4  causes the medicinal product to be expelled from the cartridge  4  through the needle unit. A cap  12  is provided to cover the needle unit when the injector is not in use. The cap  12  may be releasably secured to the housing  2  by any suitable means. 
     The dose setting means and the mean for expelling the selected dose of medicinal product will now be described in more detail. The web  6  dividing the housing  2  is a part of an insert  14  located within the housing  2 . The insert  14  comprises a first cylindrical portion  16  extending from a first side of the web  6  and second and third cylindrical portions  18 , 20  extending from a second side of the web  6 . The web  6  is provided with a circular opening  22  extending through the web  6 . 
     The first cylindrical portion  16  extends from a periphery of the web  6 . The insert  14  is secured to the housing  2  by way of the first cylindrical portion  16  by any suitable means. In the illustrated embodiment features  24  are provided within the housing  2  and on an outer surface of the first cylindrical portion  16  to enable the insert to be a snap fit to the housing  2 . 
     The second cylindrical portion  18  extends a small distance from the second aide of the web  6  about a periphery of the opening  22 . An internal surface of the second cylindrical portion is provided With a thread  26 . 
     The third cylindrical portion  20  extends substantially within the housing  2  from the second side of the web  6 . The diameter of the third cylindrical portion  20  is such that a first channel  28  is formed between an outer surface of the second cylindrical portion  20  and an inner surface of the third cylindrical portion. A second channel  30  is formed between an outer surface of the third cylindrical portion  20  and the housing  2 . 
     A piston rod  32  extends through the opening in the web  6 . The piston rod  32  is generally elongate and is provided with a thread  34  extending from a first end of the piston rod  32 . The thread  34  of the piston rod  32  engages the thread of the inner surface of the second cylindrical portion  18  of the insert  14 . The first end of the piston rod  32  is provided with a pressure foot  36 . In use the pressure foot  36  is disposed on the first side of the web  6  to about the cartridge piston  10 . 
     Ratchet means  40  are located adjacent the web  6  on the first side of the web  6 . The ratchet means  40  serve the purpose of allowing the piston rod  32  only to rotate through the insert  14  in a single direction. Due to the one piece construction of the housing, the ratchet means can be made larger than in known devices and so is stronger (more rigid). 
     A dose dial sleeve  50  of generally cylindrical form comprises a first section of first diameter and a second section of second diameter. The first section is located within the second channel  30 . An inner surface of the first section and the outer surface of the third cylindrical portion  20  are provided with interengaging features to provide a helical thread  52  between the insert  14  and the dose dial sleeve  50 . In the illustrated embodiment this was achieved by a helical track provided on the outer surface of the third cylindrical portion  20  within which a helical rib provided on the inner surface of the dose dial sleeve  50  may run. This enables the dose dial sleeve  50  to rotate about and along the third cylindrical portion  20  of the insert  14 . 
     An outer surface of the first section of the dose dial sleeve  50  is provided with graphics  53 . The graphics are typically a sequence of reference numerals. The housing  2  is provided with an aperture or window  54  through which a portion of the graphics, representing a dosage value selected by the user, may be viewed. 
     The graphics  53  may be applied to the dose dial sleeve  50  by any suitable means, in the illustrated embodiment, the graphics  53  are provided in the form of a printed label encircling the dose dial sleeve  50 . Alternatively the graphics may take the form of a marked sleeve clipped to the dose dial sleeve  50 . The graphics may be marked in any suitable manner, for example by laser marking. 
     It is an advantage of this arrangement that the helical thread  52  is formed within the dose dial sleeve between the dose dial sleeve and the insert. As can be seen this means there is no direct route from outside the injector to the working surfaces of the helical thread. Should dust or dirt enter the pen this will tend to occur between the housing and the dose dial sleeve where there are no working parts with which to interfere. This is not the case for known devices in which a helical thread is formed between the housing and an interior moving surface. In addition because of the narrower diameter of the helical thread  52  formed between the dose dial sleeve and the drive sleeve in comparison to a similar thread formed between the housing and the dose dial sleeve, the helical thread  52  is more efficient and easier to overhaul. This arrangement also produces an improvement in the dose size that can be delivered for a particular linear travel of the dose expelling means. 
     The second section of the dose dial sleeve  50  is preferably of the same outer diameter as the housing  2 . Within the dose dial sleeve  50  there is a shoulder  56  between the first section of the dose dial sleeve  50  and the second section of the dose dial sleeve  50 . 
     A drive sleeve  60  of generally cylindrical form comprises a first part of first diameter and a second part of second diameter. A first end of the first part is located within the first channel  28  of the insert  14  in the position shown in  FIG. 1 . The first part of the drive sleeve  60  may be considered as comprising a first portion aligned with a second portion. More generally in the position shown in  FIG. 1  the first portion of the drive sleeve  60  is located between the insert  14  and the piston rod  32  while the second portion is located between the piston rod  32  and the dose dial sleeve  50 . 
     A second end of the piston rod  32  end en intimal surface of the drive sleeve  60  are splined together such that no relative rotation may occur between these parts, only longitudinal displacement. 
     The outer surface of the second portion of the first part of the drive sleeve  60  is provided with a helical thread  62 . A nut  64  is provided on the helical thread  62  between the drive sleeve  60  and the dose dial sleeve  50 . The dose dial sleeve  50  and the nut  64  are splined together by spline means to prevent relative rotation between the nut  64  and the dose dial sleeve  50 . 
     The second part of the drive sleeve  60  is of larger diameter then the first part of the drive sleeve  60 . There is a step  66  between the first part of the drive sleeve  60  and the second part. The second part of the drive sleeve  60  is seated within the second section of the dose dal sleeve  50 . The shoulder  56  of the dose dial sleeve  50  and the step  66  of the drive sleeve  60  are adapted to be releasably engagable with one another to form a clutch means. When, as in  FIG. 1 , the dose dial sleeve  50  and the drive sleeve  60  are not in engagement the dose dial sleeve  50  is able to rotate with respect to the drive sleeve  60 . Conveniently, the clutch means comprises a plurality of radially extending longitudinally directed teeth provided respectively on the shoulder  56  of the dose dial sleeve  50  and the step  66  of the drive sleeve  60 . When the dose dial sleeve  50  and the drive sleeve  60  are not forced together the respective teeth will ride over one another. Preferably, the radial separation of the respective teeth corresponds to a unit dosage. 
     The second part of the drive sleeve  60  further comprises a central receiving area  68  having a peripheral recess. A button  70  of generally “T” shaped configuration is provided, the stem of which is retained within the receiving area. The stem of the button  70  is provided with a peripheral bead  71  that is retained in the peripheral recess, the button  70  being able freely to rotate with respect to the drive sleeve  60 , but being retained axially therewith. 
     Clicker moans are provided between the second section of the dose dial sleeve  50  and the second part of the drive sleeve  60 . In the illustrated embodiment, the internal surface of the second section of the dose dial  50  is provided with a plurality of longitudinally extending teeth. The radial separation of the teeth preferably corresponds to a unit dosage. The second part of the drive sleeve  60  carries a flexible toothed member  72 . Relative rotation between the dose dial sleeve  50  and the drive sleeve  60  will cause the flexible toothed member  72  to ride over the teeth to produce a series of clicks. 
     In  FIG. 1 , the injector is provided with a filed cartridge  4 . To operate the injector a user must first select a dose. To set a dose the dose dial sleeve  50  is rotated by manipulating the second section of the dose dial sleeve  50  with respect to the housing  2  until the desired dose value is visible through the window  54 . This action draws the dose dial  50  along the second cylindrical portion of the insert  14 . The drive sleeve  60  cannot rotate since it is splined to the piston rod  32 . The piston rod  32  does not rotate due to the action of the ratchet means  40 . The drive sleeve  60  is carried away from the web  6  along the piston rod  32  by the dose dial sleeve  50  as the dose dial sleeve  50  moves out from the housing  2 . The relative rotation between the dose dial sleeve  50  and the drive sleeve  60  causes the flexible toothed member  72  to ride over the ridges in the drive sleeve  60  to create a series of clicks. This is an audible confirmation of the dose being dialed. 
     Since the nut  64  is splined to the dose dial sleeve  50 , the relative rotation between the dose dial sleeve  50  and the drive sleeve  60  causes the nut  64  to process along the helical thread  62  of the drive sleeve  60 . 
     Once a desired dose has been set (as shown for example in  FIG. 2 ), to deliver the dose the user depresses the button  70  to urge the button  70  towards the first end of the housing  2 . When the button  70  is depressed the second part of the drive sleeve  60  is driven into the second section of the dose dial sleeve  50  to engage the clutch means therebetween to prevent relative rotation between the dose dial sleeve  60  and the drive sleeve  60 . The drive sleeve  60  may still rotate with respect to the button  70 . Further longitudinal movement of the button  70  causes the dose dial sleeve  50  (together with the drive sleeve  60 ) to rotate towards the fire end of the injector. Since the piston rod  32  is splined to the drive sleeve  60 , the piston rod  32  is also rotated through the insert  14  and the ratchet means  40  towards the first end of the injector, thereby to advance the cartridge piston  10  and expel the desired dose of medicinal product. The piston rod  32  continues to advance until the drive sleeve  60  and dose dial sleeve  50  have returned to their initial positions ( FIG. 3 ). 
     It can be seen that the dose selecting means and the dose expelling means extend beyond a second end of the housing  2  as the dose is selected and are returned within the housing  2  as the selected dose is expelled. 
     Further dosages may be delivered as required.  FIG. 4  shows en example of a subsequently selected dosage. It will be noted that the nut  64  has advanced further along the helical thread  62  of the drive sleeve  60 . The position of the nut  64  along the helical thread  62  corresponds to the amount of medicinal product remaining in the cartridge  4 , such that when the nut  64  reaches the end of the helical thread  62  (in the illustrated embodiment adjacent to the step  66  of the drive sleeve  60 ) and can rotate no further this corresponds to no medicinal product remaining in the cartridge  4 . It will be seen that if a user seeks to select a quantity of medical product greater than that remaining in the, cartridge  4 , this cannot be done since when the nut  64  stops rotating the dose dial sleeve  50  and the drive sleeve  60  will become locked together preventing rotation of the dose dial sleeve  50  and setting of a larger dose.  FIG. 5  shows an injector according to the present invention in which the entire medical product within the cartridge  4  has been expelled. 
     A second embodiment of the present invention is disclosed in  FIG. 6 . Like reference numerals are used to refer to like parts as between the first and second embodiments. 
     The piston rod  32 ′ shown in  FIG. 6  has e dual start thread. The piston foot  36 ′ is reversible. This has advantages in manufacture. As can be seen the structure of the insert  14 ′ has been revised. The first side of the web  6 ′ is substantially unchanged. The other side of the web is now provided with a boss  80 . A cylindrical portion  20 ′ extends away from the web  6 ′ about a periphery of the boss  80 . Threaded opening  22 ′ extends through the web  6 ′ and the boss  80 . An end of the cylindrical portion  20 ′ of the insert  14 ′ remote from the web  6 ′ is provided with a stop in the form of a land  104 . 
     The dose dial sleeve  50 ′ is of modified construction. The dose dial sleeve comprises a first cylindrical portion  84  rigidly connected to a second generally cylindrical portion  86 . An inner surface of the first cylindrical portion  84  and the outer surface of the cylindrical portion  20 ′ of the insert  14 ′ are provided with interengaging features to provide a helical thread  52 ′ between the insert  14 ′ and the dose dial sleeve  50 ′. An outer surface of the first cylindrical portion  84  is provided with the dose graphics. The housing  2 ′ is provided with an aperture or window  54 ′ through which a portion of the graphics may be viewed. 
     The second generally cylindrical portion  88  comprises a first cylindrical section  88  and a second cylindrical section  90 . The first section  88  is rigidly keyed to an inner surface of the first portion  84  of the dose dial sleeve  50 ′. The second section  90  is preferably of the same outer diameter as the housing  2 ′. Within the dose dial sleeve  50 ′ there is a shoulder  50 ′ between the first section  86  and the second section  90 . 
     A nut  64 ′ is provided on the helical thread  62 ′ between the drive sleeve  60 ′ end the first cylindrical section  86  of the dose dial sleeve  50 ′. The first cylindrical section  88  and the nut  64 ′ are splined together by spine means to prevent relative rotation between the nut  64 ′ and the dose dial sleeve  50 ′. 
     The shoulder  56 ′ of the dose dial sleeve  50 ′ and a step  66 ′ of a drive sleeve  60 ′ are adapted to be releasably engagable with on another to term a clutch means. When, as in  FIG. 6 , the dose dial sleeve  50 ′ and the drive sleeve  60 ′ are not in engagement the dose dial sleeve  50 ′ is able to rotate with respect to the drive sleeve  60 ′. Conveniently, the clutch moans comprises a plurality of radially extending longitudinally directed teeth provided respectively on the shoulder  56 ′ of the dose dial sleeve  50 ′ and the stop  88 ′ of the drive sleeve  60 ′. When the dose dial sleeve  50 ′ and the drive sleeve  80 ′ are not forced together the respective teeth will ride over one another. 
     It will be seen that the structure of the drive sleeve  60 ′ has also been modified. The second end of the piston rod  32 ′ is provided with a scooped surface within which a domed part  90  of the drive sleeve  60 ′ may extend. The domed part  90  is centrally located within a second part of the drive sleeve  60 ′ at a first end of the receiving area. 
     The button  70 ′ is of generally “T” shaped configuration. The stem of the button  70 ′ is retained within the receiving area. The stem of the button  70 ′ is provided with a peripheral bead  71 ′ that is retained in the peripheral recess, the button  70 ′ being able freely to rotate with respect to the drive sleeve  60 ′, but being retained axially therewith. 
     When the button  70 ′ is depressed the drive sleeve  60 ′ is urged into contact with the dose dial sleeve  50 ′ such that the clutch means are engaged. At the same time, the scooped surface of the piston rod  32 ′ and the domed surface of the drive sleeve approach but do not contact one another. The advantage of this structure is that it enables the overall length of the device to be reduced thereby enabling easier operation of the device when expressing fluid from a cartridge. 
     A further embodiment of the button  70 ″ and the dose dial sleeve  50 ″ can be seen in  FIG. 7 . Again like reference numerals are used to refer to like parts. In the embodiment of  FIG. 7 , the overall length of the device may be reduced still further. The second end of the piston rod  32 ″ is generally U-shaped. The limbs of the U-shape are received within a second part of the drive sleeve  60 ″. A central receiving area of the drive sleeve  60 ″ is defined by limbs (not shown) located in use between the limbs formed on the second end of the piston rod  32 ′. The button  70 ″ is of generally “T” shaped configuration. The stem of the button  70 ″ is retained within the receiving area. The stem of the button  70 ″ is provided with a peripheral bead  71 ″ that is retained in the peripheral recess, the button  70 ″ being able freely to rotate with respect to the drive sleeve  60 ″, but being retained axially therewith. 
     The second generally cylindrically portion  80 ″ of the dose dial sleeve  50 ″ comprises a first cylindrical section  88 ″ and a second cylindrical section  90 ″ connected by a radial flange  92  extending from a part of the second section, the first section  88 ″ being rigidly keyed to an inner surface of the first portion  84 ″ of the dose dial sleeve  50 ″, and the second section  90 ″ being of the same outer diameter as the housing  2 ″. 
     In each of  FIGS. 6 and 7 , there is a further modification to each of the dose dial sleeve and the insert. This may be seen more clearly with reference to  FIGS. 8 and 9 . 
     At a first end of the dose dial sleeve there is located on an internal surface a radially directed lug  100  extending generally parallel to a longitudinal axis of the sleeve. Ata second end of the insert on an external surface thereof there is provided a catch means. The catch means comprises a groove  102  extending about a central land  104 . The central land  104  is generally wedge shaped such that a first edge  106  nearer the start of the thread extends radially less far than a second opposite edge  108  located further along the thread. A sloping surface  110  is defined between the first edge  108  and the second edge  108 . Thus, when the dose dial sleeve is assembled to the insert, by threading the dose dial sleeve onto the insert, the lug  100  passes over the first edge  106  and over the sloping surface  110 . As the lug  100  passes fully over the land  104  some elastic deformation of the respective elements, the dose dial sleeve and the insert occurs. Once the lug  100  is over the land  104 , the second edge  105  of the land  104  acts as a stop to prevent removal of the dose dial sleeve from the insert. 
     The location of the second edge  108  of the land  104  is conveniently chosen at a radial location corresponding to 80 units of medicinal product, that is the maximum dose available is 80 units when the dose dial sleeve is wound from the initial position shown in any of  FIG. 1, 6 or 7  to a fully extended position with the second edge  108  of the land  104  contacting the lug  100 . 
     A fourth embodiment of the present invention is disclosed in  FIG. 10 . Like reference numerals are used to refer to like parts. 
     As can be seen the structure of the insert  14 ′″ has been revised. The first side of the web  6 ′″ substantially unchanged. The other side of the web is now provided with a boss  80 ′″. A radial flange  112  extends outwardly from the boss  80 ′″, the radial flange  112  being spaced from the web  6 ′″, and a cylindrical portion  20 ′″ extending away from the web  6 ′″ about a periphery of the radial flange  110 . A threaded opening  22 ′″ extends through the web  6 ′″ and the boss  80 ′″. 
     The dose dial sleeve  50 ′″ is of modified construction. The dose dial sleeve  50 ′″ comprises a first cylindrical portion  84 ′″ rigidly connected to a second generally, cylindrical portion  86 ′″. An inner surface of the first portion  84 ′″ and the outer surface of the cylindrical portion  20 ′″ of the insert  14 ′″ are provided with interengaging features to provide a helical thread  52 ′″ between the insert  14 ′″ and the dose dial sleeve  50 ′″. An outer surface of the first cylindrical portion  84 ′″ is provided with the dose graphics. The housing  2 ′″ is provided with an aperture or window  54 ′″ through which a portion of the graphics may be viewed. 
     The second generally cylindrical portion  86 ′″ comprises a first inner cylindrical section  88 ′″ and a second outer cylindrical section  90 ′″. The first section  88 ′″ is rigidly keyed to an inner surface of the first portion  84 ′″ of the dose dial sleeve  50 ′″. The second section  90 ′″ is preferably of the same outer diameter as the housing  2 ′″. Within the dose dial sleeve  50 ′″ there is a radial flange  94  extending between the outer section  90 ′″ and an intermediate part of the inner section  88 ′″. 
     A nut  64 ′″ is provided on a helical thread  62 ′″ formed on the drive sleeve  60 ′″. The nut  64 ′″ is disposed between the drive sleeve  60 ′″ and the second cylindrical section  88 ′″ of the dose dial sleeve  50 ′″. The second cylindrical section  88 ′″ and the nut  64 ′″ are keyed together by spline means to prevent relative rotation between the nut  64 ′″ and the dose dial sleeve  50 ′″. 
     An upper surface of the radial flange  94  of the dose dial sleeve  50 ′″ and a step  66 ′″ of the drive sleeve  60 ′″ are adapted to be releasably engagable with one another to form a clutch means. When, as in  FIG. 10 , the dose dial sleeve  50 ′″ and the drive sleeve  60 ′″ are not in engagement the dose dial sleeve  50 ′″ is able to rotate with respect to the drive sleeve  60 ′″. Conveniently, the clutch means comprises a plurality of radially extending longitudinally directed teeth provided respectively on the radial flange  94  of the dose dial sleeve  50 ″ and the step  66 ′″ of the drive sleeve  60 ′″. When the dose dial sleeve  50 ′″ and the drive sleeve  60 ″ are not forced together the respective teeth will ride over one another. 
     Example 2 
     In another embodiment of the invention ( FIG. 11 ) there is seen a drive mechanism comprising a second main housing  4 ′ having a first end and a second end. A cartridge, containing medicinal product, can be mounted to the first end of the second main housing  4 ′ and retained by any suitable means. The cartridge and its retaining means are not shown in the illustrated embodiment. The cartridge may contain a number of doses of a medicinal product and also typically contains a displaceable piston. Displacement of the piston causes the medicinal product to be expelled from the cartridge via a needle (also not shown). 
     In the illustrated embodiment, an insert  16 ′ is provided within the main housing  4 ′. The insert  16 ′ is secured against rotational and axial motion with respect to the second main housing  4 ′. The insert  16 ′ is provided with a threaded circular opening extending therethrough. Alternatively, the insert may be formed integrally with the second main housing  4 ′. 
     An internal housing  154  is also provided within the second main housing  4 ′. The internal housing  154  is secured against rotational and axial motion with respect to the second main housing  4 ′. The internal housing  154  is provided with a circular opening extending through its length in which a series of longitudinally ‘directed splines are formed. A helical thread  150  extends along the outer cylindrical surface of the internal housing  154 . Alternatively, the internal housing may be formed integrally with the second main housing  4 ′ and/or with the insert  16 ′. 
     A first thread  19 ′ extends from a first end of a piston rod  20 ″. The piston rod  20 ″ is of generally circular section. The first end of the piston rod  20 ″ extends through the threaded opening in the insert  16 ′ and the first thread  19 ′ of the piston rod  20 ″ is engaged with the thread of the insert  16 ′. A pressure foot  22 ″ is located at the first end of the piston rod  20 ″. The pressure foot  22 ″ is disposed to abut a cartridge piston (not shown). A second thread  24 ′ extends from a second end of the piston rod  20 ″. The first thread  19 ′ and the second thread  24 ′ are oppositely disposed. 
     A drive sleeve  30 ′ extends about the piston rod  20 ″. The drive sleeve  30 ′ is generally cylindrical. The drive sleeve  30 ′ is provided at a first end with a first radially extending flange  32 ″. A second radially extending flange  34 ′ is provided, spaced a distance along the drive sleeve  30 ′ from the first flange  32 ″. An external helical thread (not shown) is provided on the outer part of the drive sleeve  30 ′ Wending between the first flange  32 ″ and the second flange  34 ′. An internal helical thread extends along the internal surface of the drive sleeve  30 ′. The second thread  24 ′ of the piston rod  20 ″ is engaged with the internal helical thread of the drive sleeve  30 ′. 
     A nut  40 ′ is located between the drive sleeve  30 ′ and the internal housing  154 , disposed between the first flange  32 ″ and the second flange  34 ′ of the drive sleeve  30 ′. The nut  40 ′ can be either a ‘half-nut or a ‘full-nut’. The nut  40 ′ has an internal thread that is engaged with the external helical thread of the drive sleeve  30 ′. The outer surf-ace of the nut  40 ′ and an internal surface of the internal housing  154  are keyed together by means of longitudinally directed splines to prevent relative rotation between the nut  40 ′ and the internal housing  154 , while allowing relative longitudinal movement therebetween. 
     A clicker  50 ″″ and a clutch  60 ″″ are disposed about the drive sleeve  30 ′, between the drive sleeve  30 ′ and the internal housing  154 . 
     The clicker  50 ″″ is located adjacent the second flange  34 ′ of the drive sleeve  30 ′. The clicker  50 ″″ includes at least one spring member (not shown). The clicker  50 ″″ also includes a set of teeth (not shown) having a triangular profile disposed towards the second end of the drive mechanism. When compressed, the at least one spring member of the clicker  50 ″″ applies an axial force between the flange  34 ′ of the drive sleeve  30 ′ and the clutch  60 ″″. The outer surface of the dicker  50 ″″ and an internal surface of the internal housing  164  are keyed together by means of longitudinally directed splines to prevent relative rotation between the dicker  50 ″″ and the internal housing  154 , while allowing relative longitudinal movement therebetween. 
     The clutch  60 ″″ is located adjacent the second end of the drive sleeve  30 ′. The clutch  60 ″″ is generally cylindrical and is provided at its&#39; first end with a plurality of teeth of triangular profile disposed about the circumference (not shown), that act upon the teeth of the clicker  50 ″″. Towards the second end of the clutch  60 ″″ there is located a shoulder  158 . The shoulder  158  of the clutch  60 ″″ is disposed between the internal housing  154  and a radially inwardly directed flange of the dose dial grip  76 ′ (described below). The shoulder  158  of the clutch  60 ″″ is provided with a plurality of dog teeth (not shown) extending in the direction of the second end of the drive mechanism. The clutch  60 ″″ is keyed to the drive sleeve  30 ′ by way of splines (not shown) to prevent relative rotation between the clutch  60 ″″ and the drive sleeve  30 ′. 
     A dose dial sleeve  70 ′″ is provided outside of the internal housing  154  and radially inward from the second main housing  4 ′. A helical thread is provided on an inner surface of the dose dial sleeve  70 ′″. The helical thread of the dose dial sleeve  70 ′″ is engaged with the helical thread  150  of the internal housing  154 . 
     The second main housing  4 ′ is provided with a window (not shown) through, which part of the outer surface of the dose dial sleeve  70 ″ may be viewed. Conveniently, a visual indication of the dose that may be dialed, for example reference numerals (not shown), is provided on the outer surface of the dose dial sleeve  70 ′″. Conveniently, the window of the second main housing  4 ′ allows only the dose that is currently dialed to be viewed. 
     A dose dial grip  76 ′ is located towards the second end of the drive mechanism. The dose dial grip  76 ′ is secured against rotational and axial motion within respect to the dose dial sleeve  70 ′″. The dose dial grip  76 ′ is provided with a radially inwardly directed flange  160 . The radially inwardly directed flange  160  of the dose dial grip  76 ′ is provided with a plurality of dog teeth (not shown) extending in the direction of the first end of the drive mechanism to abut the dog teeth of the clutch  60 ″″. Coupling and decoupling of the dog teeth of the dose dial grip  76 ′ with the dog teeth of the clutch  60 ″″ provides a releasable clutch between the dose dial grip  76 ′ and the clutch  60 ″″. 
     A button  87  of generally T shaped cross-section is provided at a second end of the drive mechanism. A cylindrical feature of the button  82 ′ extends towards the first end of the drive mechanism, through an opening in the dose dial grip  76 ′ and into a recess in the drive sleeve  30 ′. The cylindrical feature of the button  82 ′ is retained for limited axial movement in the drive sleeve  30 ′ and against rotation with respect thereto. The cylindrical feature of the button  82 ′ has lugs extending radially (not shown) that abut the second surface of the shoulder  158  of the clutch  60 ″″. The second end of the button  82 ′ is generally circular and has a cylindrical skirt about its&#39; periphery that descends towards the first end of the drive mechanism. The skirt of the button  87  is located radially inward from the dose dial grip  76 ′. 
     Operation of the drive mechanism in accordance with the present invention will now be described. 
     To dial a dose, a user rotates the dose dial grip  76 ′. The spring member of the clicker  50 ″″ applies an axial force to the clutch  60 ″″ in the direction of the second end of the drive mechanism. The force exerted by the spring member of the clicker  60 ″″ couples the dog teeth of the clutch  60 ″″ to the dog teeth of the dose dial grip  76 ′ for rotation. As the dose dial grip  76 ′ is rotated, the associated dose dial sleeve  70 ″″, the drive sleeve  30 ′ and the clutch  60 ″″ all rotate in unison. 
     Audible and tactile feedback of dose being dialed is provided by the clicker  50 ″ and the clutch  60 ″″. As the clutch  60 ″″ is rotated, torque is transmitted from the teeth at the first end of the clutch  80 ″ and the teeth of the clicker  50 ″″. The clicker  50 ″″ cannot rotate with respect to the internal housing  154 , so the at least one spring member of the clicker  50 ″″ deforms allowing the teeth of the clutch  60 ″″ to jump over the teeth of the clicker  50 ″″ producing an audible and tactile ‘click’. Preferably, the teeth of the clicker  50 ″″ and the teeth of the clutch  60 ″″ are disposed such that each ‘click’ corresponds to a conventional unit of the medicinal product, or the like. 
     The helical thread of the dose did sleeve  70 ″″ and the internal helical thread of the drive sleeve  30 ′ have the same lead. This allows the dose dial sleeve  70 ′″ to advance along the thread  150  of the internal housing  154  at the some rate as the drive sleeve  30 ′ advances along the second thread  24 ′ of the piston rod  20 ″. 
     Rotation of the piston rod  20 ″ is prevented due to the opposing direction of the first thread  19 ′ and the second thread  24 ′ of the piston rod  20 ″. The first thread  19 ′ of the piston rod  20 ″ is engaged with the thread of the insert  16 ′ and so the piston rod  20 ″ does not move with respect to the second main housing  4 ′ while a dose is dialed. 
     The nut  40 ′, keyed to the internal housing  154 , is advanced along the external thread of the drive sleeve  30 ′ by the rotation of the drive sleeve  30 ′. When a user has dialed a quantity of medicinal product that is equivalent to the deliverable volume of the cartridge, the nut  40 ′ reaches a position where it abuts the second flange  34 ′ of the drive sleeve  30 ′. A radial stop formed on the second surface of the nut  40 ′ contacts a radial stop on the first surface of the second flange  34 ′ of the drive sleeve  30 ′, preventing both the nut  40 ′ and the drive sleeve  30 ′ from being rotated further. 
     Should a user inadvertently dial a quantity greater than the desired dosage, the drive mechanism allows the dosage to be corrected without dispense of medicinal product from the cartridge. The dose dial grip  78 ′ is counter-rotated. This causes the system to act in reverse. The torque transmitted through the clutch  60 ″″ causes the teeth at the first end of the clutch  60 ″″ to ride over the teeth of the clicker  50 ″″ to create the clicks corresponding to the dialed dose reduction. 
     When the desired dose has been dialed, the user may then dispense this dose by depressing the button  82 ′ in the direction of the first end of the drive mechanism. The lugs of the button  82 ′ apply pressure to the second surface of the shoulder  158  of the clutch  60 ″″, displacing the clutch  60 ″″ axially with respect to the dose dial grip  76 ′. This causes the dog teeth on the shoulder  168  of the clutch  60 ″″ to disengage from the dog teeth of the dose dial grip  76 ′. However, the clutch  60 ″″ remains keyed in rotation to the drive sleeve  30 ′. The dose dial grip  76 ′ and associated dose dial sleeve  70 ′″ are now free to rotate (guided by the helical thread  150  of the internal housing  154 ). 
     The axial movement of the clutch  60 ″″ deforms the spring member of the dicker  50 ″ and couples the teeth at the first and of the clutch  60 ″ to the teeth of the clicker  50 ″ preventing relative rotation therebetween. This prevents the drive sleeve  30 ′ from rotating with respect to the internal housing  154 , though it is still free to move axially with respect thereto. 
     Pressure applied to the button  82 ′ thus causes the dose dial grip  76 ′ and the associated dose dial sleeve  70 ′″ to rotate into the second main housing  4 ′. Under this pressure the clutch  60 ″″, the dicker  50 ″″ and the drive sleeve  30 ′ are moved axially in the direction of the first end of the drive mechanism, but they do not rotate. The axial movement of the drive sleeve  30 ′ causes the piston rod  20 ″ to rotate through the threaded opening in the insert  16 ′, thereby to advance the pressure foot  22 ″. This applies force to the piston, causing the medicinal product to be expelled from the cartridge. The selected dose is delivered when the dose dial grip  76 ′ returns to a position where it abuts the second main housing  4 ′. 
     When pressure is removed from the button  82 ′, the deformation of the spring member of the dicker  50 ″″ is used to urge the clutch  60 ″″ back along the drive sleeve  30 ′ to re-couple the dog teeth on the shoulder  158  of the clutch  60 ″″ with the dog teeth on the dose dial grip  76 ′. The drive mechanism is thus reset in preparation to dial a subsequent dose.