Abstract:
An assembly for the administration of a selected dosage of insulin or other medicaments from a cartridge by moving a plug guided in said cartridge, comprises an adapter assembly for adapting cartridges with different dimensions or contents. The adapter assembly comprises a first threaded element threaded with a thread lead and movable in a moving direction to move the plug, and a second threaded element threaded with a thread lead for setting a selected dosage, pivotably screwed to said first threaded element and limiting the movement of said first threaded element, and wherein said thread lead of said first element and said thread lead of said second threaded element are adapted to the dimensions and/or the contents of said cartridge.

Description:
CROSS REFERENCE TO RELATED PATENT APPLICATIONS 
       [0001]    This patent application is filed herewith for the U.S. National Stage under 35 U.S.C. §371 and claims priority to PCT application PCT/EP2010/054383, with an international filing date of 31 Mar., 2010 and a Convention priority date of 1 Apr. 2009. The contents of this application are incorporated in their entirety herein. 
     
    
     STATEMENT REGARDING FEDERALLY-SPONSORED RESEARCH OR DEVELOPMENT 
       [0002]    Not applicable. 
       TECHNICAL FIELD 
       [0003]    The invention relates to an assembly to administer a selected dosage of insulin or other medicaments from a cartridge by feed movement of a plug movably guided in the cartridge. 
       BACKGROUND OF THE INVENTION 
       [0004]    Such application assemblies are particularly employed in insulin therapy for diabetes mellitus. In insulin therapy, particularly in the intensified insulin therapy and conventional insulin therapy, insulin is not applied in constant amounts. In conventional insulin therapy insulin is applied at pre-scheduled times. The daily routine of a patient complies with such times. In intensified conventional insulin therapy a basal requirement of insulin is provided, often by a slow acting and long lasting insulin, the basal insulin. At meals, a fast-acting insulin is applied. The dosage of the fast-acting insulin is essentially based on the comprised carbohydrates. The dosage is hence specifically chosen depending on external circumstances. Such circumstances are, for example, the time of the day, the amount of exercise, the diet and the like. 
         [0005]    Diabetes mellitus can have severe long-term consequences and impairment of the body. They can be considerably reduced by means of an adapted insulin therapy, preferably an intensified conventional insulin therapy. A wrong dosage can also have short term effects like hypoglycemia. An optimal adjustment of the dosage to the respective circumstances is, therefore, highly desirable. 
         [0006]    For this reason diabetes mellitus patients are urged to take minutes of their lifestyle and applied doses of insulin. The record keeping is time consuming. The record usually comprises the measured blood sugar level, the consumed amount of carbohydrates, the applied dosage of insulin as well as time and date. The attending physician or the patient can determine or adjust the respective dosage using this record. 
         [0007]    The administration of insulin is carried out with an injection aid (also known as pen), that is provided with an injection needle and a cartridge containing the medicament or with an insulin pump with a cartridge. The insulin pump is employed continuously whereas a pen is employed for single application procedures. 
         [0008]    Known pens externally resemble a large ball pen. They comprise a housing and a cartridge. Cartridge is understood to be a cylindrical ampoule having a puncturable membrane on one side. The other side is closed by a movable plug. The medicament is contained in the cartridge. The cartridge is usually exchangeable. However, assemblies are known that are provided as disposable pens. Cartridges, their content, dimensions and their handling are not standardized. Therefore, a cartridge of one manufacturer can normally not be inserted into a pen of another manufacturer. 
         [0009]    A pen comprises a measuring device. The required dosage is adjusted with a dose setting knob. It is then applied into the hypodermic fat tissue. Some pens display the adjusted dosage on a display with electrical energy instead of a mechanical display. The display is driven by a coin cell. The patient can adjust the dosage and note it down in the record. The diabetes log is shown to a physician. The physician can work out the further therapy together with further body parameters i.e. blood sugar values, body measurements and blood pressure. 
         [0010]    Keeping records according to known methods is time consuming. It can lead to carelessness of the patient. There is a danger of knowingly or unknowingly wrong recording of the insulin dosage. This can, for example, occur if the patient acts contrary to the physician&#39;s instructions. The patient usually does not like to disclose a faulty self medication. Hence, the data on the record and the adaption of the prospective therapy will be wrong. The patient will suffer severe acute or long term consequences. 
         [0011]    DE 101 47 973 A1 discloses an assembly where sensors are provided for the detection of the kind of cartridge in order to prevent mistakes. For this purpose, sensors are attached to the assembly, which interact with cognitional elements on a cartridge. Thereby, the medicament in a cartridge unambiguously read out. 
         [0012]    DE 10 2005 018 305 A1 discloses an application assembly, where a dosage application knob is secured against accidental actuation. An adjustment ring is provided on one end of the application assembly for adjustment of a dosage. The dosage application knob is positioned separate from the adjustment ring and only serves for the application of an adjusted dosage. The applied dosage can be adjusted with the adjustment ring. The actuator is glidingly held in the adjustment ring. By rotating the adjustment ring the dosage application knob is displaced in axial direction. The actuator never rises beyond the adjustment ring. This serves as securing means to prevent that the dose is accidentally actuated. 
         [0013]    In the prior art it is disadvantageous that the patient must use different pens for insulin of different manufacturers. This forces the patient to learn a new handling. Furthermore, it is disadvantageous that different insulin pens are provided with different security mechanisms to prevent accidental activation. 
       BRIEF SUMMARY OF THE INVENTION 
       [0014]    It is an object of the invention to provide an assembly of the aforementioned kind that is more cost effective an easier to handle. It is a further object of the invention to provide an assembly with a more secure handling. 
         [0015]    According to the present invention this object is achieved with an application assembly of the aforementioned kind by 
         [0016]    (a) an adapter assembly to adapt cartridges with different dimensions or contents, comprising 
         [0017]    (b) a first threaded element movable in a moving direction to move the plug, and 
         [0018]    (c) a second threaded element for adjusting a selected dosage, pivotably screwed to the first threaded element and limiting the movement of the first threaded element, wherein 
         [0019]    (d) the thread lead of the first and the second threaded element is adapted to the dimensions and/or the contents of the cartridge. 
         [0020]    Insulins of different suppliers are offered in different cartridge sizes. An assembly according to the invention enables the user to use the same pen for insulins of different suppliers. This reduces the purchase costs, because there is no need to buy a new pen upon change of the medicament. The user has the advantage that he does not need to get used to the handling of a new application assembly. The handling is, therefore, facilitated and more secure. 
         [0021]    Cartridges provided by different suppliers may have different outer dimensions. Hence, a cartridge of a different supplier can usually not be inserted into the pen known in the art. An adapter assembly will compensate such drawbacks. Cartridges provided by different suppliers may be used. The flank lead of the threaded elements defines the feed movement of the plug. Thereby, it is ensured that the applied dosage does not depend on the shape of the cartridge. An individual specific flank lead is assigned to each kind of cartridge. 
         [0022]    The invention is based on the finding that the integration of threaded elements with matching flank leads allows the use of different cartridges. The cartridges may have different dimensions and contents. Accordingly, the feed movement of the plug is different for different cartridges. 
         [0023]    Preferably, the assembly comprises a pivotable dose setting knob and means for transferring the rotational movement of the dose setting knob to the second threaded element. In particular, the dose setting knob may be locked. In a particularly preferred embodiment of the present invention a housing is provided, the dose setting knob adapted to be pressed inside against the force of a pressure spring in the housing and which dose setting knob is adapted to be releasably locked therein. The dose setting knob operates similarly to the mechanics of a ball pen. In order to use the assembly the dose setting knob is released and is pushed outside by the spring. It may then be rotated in the desired way. The dose is selected by rotation. The rotational movement is transmitted to the threaded element. In order to administer the medicament the dose setting knob is pushed. If the assembly is not used the dose setting knob is pressed inside and secured against accidental actuation. 
         [0024]    According to a modification of the invention it is provided, that 
         [0025]    (a) the first threaded element is formed by a threaded rod with an external, male thread, 
         [0026]    (b) the adapter assembly comprises a casing having an open side for receiving a cartridge and which is provided with an aperture at its opposite end for guiding the threaded rod in a rotationally secured way, and 
         [0027]    (c) the second threaded element is formed by a nut, screwed on the threaded rod from the outside of the casing, the axial position of which is selected by rotation. 
         [0028]    The production of such an assembly is cost effective and the design is simple. It is understand that it is possible to use a threaded hollow shaft or the like. Any other securing means may be used instead of a casing for an adapter. 
         [0029]    Preferably, securing means may be provided to block a movement of the threaded rod in an opposite movement direction. 
         [0030]    The securing means ensure that the adapter may be used only once. With the securing means the threaded element cannot be returned to the starting position. Once insulin has been applied no new cartridge can be inserted. The adapter needs to be replaced. The mechanical wear and tear of the components is reduced because the adapter can only be used once. The application assembly works more precise and more reliable. 
         [0031]    Preferably, the securing means are formed by a securing disk attached to the threaded rod inside the casing which is locked by the cartridge. 
         [0032]    The securing means can be formed by a disk attached to the threaded rod with an opening between the front end of the cartridge and the inner front end of the casing and having flexible tongues in the range of the opening engaging with the thread of the threaded rod. 
         [0033]    Such a securing disk is cost effective in production and reliable in handling. It is understood that the securing means can also be provided at the casing. 
         [0034]    In a preferred embodiment of the invention a sensor assembly is provided for contactless registration of the applied dosage. By not using mechanical parts wear and tear is reduced and therefore, the reliability of the application assembly is improved. The sensor assembly may contain: 
         [0035]    (a) magnets on one of the rotating components for adjusting the dosage, 
         [0036]    (b) magnetic sensors detecting the rotation of the magnets, and 
         [0037]    (c) processing, and display means for processing and/or displaying a dosage corresponding to the detected movement determined from the detected rotation. 
         [0038]    Magnets are well suited for the contactless transmission of signals, because magnetic fields are spatially extended. Sensors can detect magnetic fields without being in mechanic contact to the magnets. The magnetic fields of magnets remain constant over a long period of time, thus the reliability of the application assembly is improved. 
         [0039]    Preferably, means are provided for determining and registering the time and/or the date and means for determining and registering the selected and administered dosage. By saving the date and/or the time together with the adjusted dosage the patient can easily monitor when he applied insulin for the last time. For basal insulin it is important to meet exact application times of insulin. This is realized by the indication of the elapsed time since the last administered dosage. With such an arrangement the patient can control when he administered the last dosage. This is helpful if the patient wants to control the development of the blood sugar values since the last dosage of insulin. Furthermore, the selected dosage of insulin can be saved. The patient can then reconstruct if the applied dosage was correctly calculated. 
         [0040]    The date and/or the time may be transmitted to a receiver by means of a transmitter together with the signal of the applied amount of the medicament. The data may also be recorded and transmitted independently. 
         [0041]    In order to reduce the transmission distance the signal can be transmitted to, for example, a cell phone by a short range broadcast standard (such as, for example, Bluetooth®). The further transmission can then be effected by a common mobile telephone network. It is understood that any other transmission is also possible. Thus, the information may also be transmitted to a receiver which is connected to the internet. Also, GSM and the like are suited for the transmission of the signal. The transmitted data may be encrypted. 
         [0042]    The assembly can also be provided with a receiver for receiving data. Thereby, notices of receipt, warnings or any other data can be received. In particular, an assembly with a receiver enables the communication with the physician in charge even if another communication is not possible. 
         [0043]    The assembly may be provided with a display for showing warnings, transmission data, status information and the like. This facilitates the handling. 
         [0044]    Furthermore, the assembly may be provided with means for acoustic in- and/or output of data. During the course of the disease impaired vision can occur for diabetics. The use of an acoustic in- and/or output of data ensures that even these patients can handle an injection aid. 
         [0045]    The assembly may be provided with a touch pad for the in- and output of data and dosage settings. Such a touch pad can be designed for blind users in order to enable blind users to use such an application assembly, too. 
         [0046]    The energy storage can be exchangeably arranged so that the functionality is ensured at any time. Alternatively, the assembly may be provided with a wireless chargeable and/or exchangeable energy storage. It may then easily remain with the patient at all times. The energy storage can be wirelessly charged by electromagnetic induction like an electrical toothbrush. 
         [0047]    The assembly can be used in a network for the transmission, saving and processing of data relating to the dosage of a medicament. The network may be provided with an application assembly with a transmitter for the transmission of data relating to the selected and/or administered dosage of a medicament, a receiver for receiving the signal and a data processing unit for saving and processing the received data. 
         [0048]    Personalized data may be saved in the data processing unit and means may be provided for processing the data transmitted by the transmitter together with the personalized data. 
         [0049]    The network may comprise a base station which collects data of the application assembly and transmits them to the data processing unit. The signals of the application assembly may be wireless transmitted. The transmission between the base station and the data processing unit may be effected via a mobile telephone network. 
         [0050]    Further modifications of the invention are subject matter of the subclaims. Preferred embodiments are described below in greater detail with reference to the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
         [0051]      FIG. 1  is a cross section through an application assembly for insulin with mechanical setting of the dosage; 
           [0052]      FIG. 2  shows an adapter with a cartridge to adapt the cartridge to the application assembly of  FIG. 1  in greater detail; 
           [0053]      FIG. 3  is a cross section of the application assembly of  FIG. 1  perpendicular to its longitudinal axis; 
           [0054]      FIG. 4  schematically shows the setup of a network for an application assembly according to  FIG. 1  with a data processing unit where patient data are stored; 
           [0055]      FIG. 5(   a - f ) shows cross sections along three different sectional planes of the assembly in  FIG. 1  with different orientations of the dosage means; 
           [0056]      FIG. 5   g  shows a cross section through an application assembly as in  FIG. 1  with the three different sectional planes of  FIG. 5(   a - f ) shown; 
           [0057]      FIG. 6  is an exploded view of the mechanical set-up of the application assembly of  FIG. 1  which controls the movement of the dose setting knob along the longitudinal axis of the assembly; 
           [0058]      FIG. 7  is a longitudinal cross section of an alternative embodiment of an application assembly where the dosage is contactless measured; 
           [0059]      FIG. 8  shows an adapter of  FIG. 7  in detail with a cartridge to adapt to an application assembly for insulin; 
           [0060]      FIG. 9(   a - c ) illustrates the locking mechanism during the dosing of insulin with an assembly of  FIG. 7 ; 
           [0061]      FIG. 10   a  is an exploded view of the cartridge side portion of the assembly of  FIG. 7 ; 
           [0062]      FIG. 10   b  is an exploded view of the dose setting knob side portion of the assembly of  FIG. 7 ; 
           [0063]      FIG. 11   a  is an exploded view of a portion of the mechanical set-up of  FIG. 10   b  in greater detail; 
           [0064]      FIG. 11   b  is an exploded view of another part of the mechanical set-up and the dose setting knob of  FIG. 10   b ; and 
           [0065]      FIG. 12(   a - d ) are cross sections perpendicular to the longitudinal axis of an application assembly of  FIG. 7  in different positions. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0066]    In  FIG. 1  an application assembly for insulin is generally denoted with numeral  10 . The application assembly is provided with an elongated plastic housing. The housing comprises a front portion  14 , a back portion  16 , an intermediate portion  15  arranged between the front and the back portions  14  and  16 , respectively, of the housing and an end portion  12 . The front portion  14  of the housing is covered by an elongated cap  18 . 
         [0067]    An essentially cylindrical cartridge  20  is arranged inside the front portion  14  of the housing. The cartridge  20  is filled with insulin. The cartridge  20  is provided with a membrane  22 . For administering the insulin a needle (not shown) can be inserted through the membrane  22 . 
         [0068]    The cartridge  20  is also provided with a plug  24  movably guided in an axial direction. The diameter of cartridges generally varies depending on the manufacturer. An adapter assembly is used to account for such variations. The adapter assembly has an exchangeable casing  28 , a threaded rod  38 , a nut  40  and a disk  34  and is described below in greater detail. Different adapter assemblies are used for different corresponding cartridges  20 . The cartridge  20  is tightly supported in the adapter assembly. A dose setting knob  69  described below is present at the back portion  16  of the housing. 
         [0069]    The adapter assembly comprises a casing  28 . The cartridge  20  is arranged inside such casing  28 . The casing  28  is essentially designed as a hollow cylinder. The inner diameter of the casing  28  corresponds to the outer diameter of the cartridge  20 . The outer diameter of the casing  28  corresponds to the diameter of a cylindrical interior space of the front portion  14  of the housing. The casing  28  serves as an adapter for different cartridge shapes. 
         [0070]    The components  28 ,  38 ,  34 ,  40  of the adapter assembly are shown with a cartridge  20  in  FIG. 2  in greater detail. The casing  28  is open at the cap end in order to enable the cartridge to be inserted when the front portion  14  of the housing is opened. The end of the casing  28  on the side of the dose setting knob  69  is closed and is provided with a central aperture  30 . The aperture  30  is a circular opening with three inwardly rising radial projections. On the side of the dose setting knob  69  the front end of the cartridge  28  is provided with axial projections  32  form-fittingly engaging with depressions in the intermediate portion  15 . Thereby, the casing  28  is secured against rotation. 
         [0071]    The disk  34  essentially consists of sheet metal and is arranged adjacent to the closed end of the casing  28  on the side of the dose setting knob  69 . The disk  34  is clamped between the cartridge  20  and the closed end of the casing  28 . This is shown in  FIG. 2 . In  FIG. 2  the disk is separately shown outside the casing  28  for better illustration. The disk  34  is also provided with a central opening  36 . The opening  36  is star shaped. Thereby, small, concentric elastic sheet metal tongues  37  are formed. The number of elastic sheet metal tongues  37  depends on the symmetry of the star shaped opening  36 . In the present case the disk  34  has six sheet metal tongues  37 . Obviously, any other number of tongues is also suitable. The threaded rod  38  may be moved in an axial direction from the top in  FIG. 1  through the aperture  30  and the opening  36  in the disk  34 . 
         [0072]    The threaded rod  38  is shape such that it corresponds to the form of the aperture  30 . Thereby, the threaded rod  38  is secured against rotation with respect to the casing. 
         [0073]    The threaded rod  38  is provided with a male, exterior thread. The elastic sheet metal tongues  37  engage with the threads of the threaded rod  38 . Upon axial movement of the threaded rod  38  in the direction of the cartridge  20  the metal sheet tongues  37  are slightly bent. A movement of the threaded rod  38  in the reverse direction is prevented by the metal sheet tongues  37 . The threaded rod  38  can only be axially moved in the direction of the cartridge. Insulin is pushed through the injection needle like a syringe upon axial, in  FIG. 2  downward movement of the threaded rod  38  and the plug  24 . 
         [0074]    A nut  40  with a female thread is screwed onto the threaded rod  38  outside the casing  28 . On its outside the nut  40  is provided with radial cams  42  for guiding the nut. Before putting a full cartridge into use the nut  40  touches the end of the casing  28  at the side of the dose setting knob. This is shown in  FIG. 1 . Upon rotation the nut  40  moves up in  FIG. 1  relative to the casing. Thereby, a gap occurs between the nut  40  and the casing  28  which is fixed to the housing. Thereby, the plug  24  is not yet influenced. In order to administer insulin a pressure is applied to the threaded rod  38  and hence to the plug  24 . In doing so, the threaded rod  38  is pushed downwards in  FIG. 1  in the direction of the cap  18 . 
         [0075]    The upper end ( FIG. 1 ) of the casing  28  forms a stop for the movement of the threaded rod  38  with the nut  40 . The gap generated by rotating the nut  40  corresponds to the stroke travelled by the plug and is a measure for the administered dosage of insulin. 
         [0076]    The slope of the thread of the threaded rod  38  is adapted to the geometry of the cartridge  20  and the applied insulin. A cartridge with a smaller diameter requires a greater slope than a cartridge with larger diameter for the same insulin and the same volume. One turn of the threaded rod  38  corresponds to a certain stroke and hence an administered dosage of insulin. 
         [0077]    The dosing by rotating the nut  40  is carried out by means of a dosing means described below. The dosing means is arranged in the back portion  16  of the housing. This can be seen in  FIGS. 1 and 6 . The adapter assembly and the dosing means serve to select the dosage. 
         [0078]    The dosing means comprises a jacket  46  with a cylindrical socket  47 . With the cylindrical socket  47  the jacket  46  is pivotably mounted in a bearing sleeve  48 . The inner wall of the jacket  46  is provided with axial grooves  45 . The cams  42  of the nut engage with the grooves  45  and are axially movable therein. 
         [0079]    A rotational movement of the jacket  46  is hence transferred to the nut  40 . The nut  40  moves in an axial direction on the non-rotatable threaded rod  38 . An axially movable, hollow shaft  50  is coaxially provided inside the jacket  46 . At its end hidden inside the jacket  46  the hollow shaft  50  is provided with projections  51  extending in an axial direction along the circumference also engaging with the grooves  45  in the inner wall of the jacket  46 . The jacket  46  hence follows a rotation of the hollow shaft  50 . 
         [0080]    The hollow shaft  50  is provided with a thickened portion  52  along the circumference at its dose setting knob end. The thickened portion  52  extends over a cylindrical range  54  ending at a surrounding edge  55  with a larger diameter. The thickened portion  52  serves as a counter bearing for a pressure spring  53  coaxially arranged around the hollow shaft  50 . The pressure spring  53  is shown in  FIG. 1 . The counter bearing of the pressure spring  53  on the side of the cartridge is formed by the bearing sleeve  48 . 
         [0081]    The pressure spring  53  pushes the hollow shaft  50  from the jacket  46 . The stroke is limited by a release spring  96  stopping the surrounding edge on the side of the dose setting knob. The release spring  96  is shown in  FIG. 1 . There is a gap between the nut  40  and the hollow shaft  50 . 
         [0082]    If the patient rotates the hollow shaft  50  the nut  40  is shifted in the jacket  46  in the direction of the dose setting knob  69 . Thereby, the gap between the hollow shaft  50  and the nut  40  is reduced. At the same time the gap between the upper end, in  FIG. 1 , of the casing  28  and the nut  40  is increased. By exertion of a force onto the hollow shaft  50  downwards in  FIG. 1  the compression spring  53  is compressed. The gap between the hollow shaft  50  and the nut  40  is reduced. Once the hollow shaft  50  touches the nut  40 , the nut  40  moves in the direction of the cap  18  upon further application of a force onto the hollow shaft  50 . As the nut is connected to the threaded rod  38  by the thread the threaded rod is shifted in the direction of the cap  18  until the nut meets the dose setting knob end of the casing  28 . 
         [0083]    The range  54  is surrounded by a conducting tube  56 . The conducting tube  56  is shown in  FIG. 1 . Metal contacts are attached to bearing sleeve  48  on the side of the dose setting knob. A switch is formed by interaction with the conducting tube  56 . 
         [0084]    Closing the switch indicates that insulin is administered. The opening of the switch is used as a switch-on post. In a different embodiment (not shown) a magnetically induced sensor mechanism is provided which realizes the switching operations by moving a magnet fixed to the bearing sleeve  48  relative to a magnetic sensor attached to a printed circuit board. 
         [0085]    On its outside the jacket  46  is divided into three portions. A first portion is provided with several radial projections  59  on the circumference. Movable latching elements  33   a  and  33   b  (shown in  FIG. 3 ) provided in the back portion  16  of the housing engage with the projections  59 . Thereby, the rotational movement of the jacket  46  is divided into angular steps. The division is chosen in such a way that every latching in the next position corresponds to a rotation of the hollow shaft  50  by 30°. 
         [0086]    A second portion of the jacket  46  is provided with three axial cam discs  61 ,  130  and  132 . Each cam disc  61  comprises two diametrically opposite cams  134 ,  136 ,  138 ,  140 ,  141  and  142 . The cam discs  61  are angularly displaced by 60° with respect to each other. A spring contact  63 ,  144  and  146  is provided in the back portion  16  of the housing on the same axial level as each cam disk  61 ,  130  and  132 . This is shown in  FIG. 5 . The spring contacts  63 ,  144  and  146  are attached to a circuit board  60 . The circuit board  60  is positioned in the back portion  16  of the housing ( FIG. 3 ). 
         [0087]    Upon rotation of the jacket  46  the spring contacts  63 ,  144  and  146  are alternately moved by the cams  134 ,  136 ,  138 ,  140 ,  141  and  142 . Thereby, the contacts are opened or closed.  FIG. 5  shows the cams  134 ,  136 ,  138 ,  140 ,  141  and  142  and the position of the spring contacts  63 ,  144 ,  146  for a counter-clockwise rotation. A counter-clockwise rotation results in positions shown in the spreadsheet below. A closed contact is represent by 1 an open contact by 0. 
         [0000]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                   
                   
               
               
                   
                 Figure 
                 pivot angle 
                 cam disk A 
                 cam disk B 
                 cam disk C 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 5a 
                  0° 
                 1 
                 0 
                 0 
               
               
                   
                 5b 
                  30° 
                 1 
                 1 
                 0 
               
               
                   
                 5c 
                  60° 
                 0 
                 1 
                 0 
               
               
                   
                 5d 
                  90° 
                 0 
                 1 
                 1 
               
               
                   
                 5e 
                 120° 
                 0 
                 0 
                 1 
               
               
                   
                 5f 
                 180° 
                 1 
                 0 
                 1 
               
               
                   
                   
               
             
          
         
       
     
         [0088]    Starting from a position with a pivot angle of 0° a counter-clockwise rotation leads to the following encoding for the first 30° rotation: 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                   
               
               
                   
                 pivot angle 
                 cam disk A 
                 cam disk B 
                 cam disk C 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                    0° 
                 1 
                 0 
                 0 
               
               
                   
                 −30° 
                 1 
                 0 
                 1 
               
               
                   
                   
               
             
          
         
       
     
         [0089]    The rotating direction of the jacket  46  can be unambiguously assigned by the order in which the contacts open (0) and close (1). A corresponding insulin dosage is related to the sequence of the switch positions. The third contact essentially serves for reliability and can be used to detect errors. 
         [0090]    The hollow shaft  50  is provided with a first claw  65  on the side of the dose setting knob. This is shown in  FIG. 6 . A second claw  67  of an extension  62  engages with the first claw  65  of the hollow shaft  50 . The extension  62  is also hollow. The second claw  67  is provided on the cap side of the extension  62 . The dose setting knob  69  is attached on the other side of the extension. When the patient rotates the dose setting knob, the extension  62  follows the rotational movement. The extension  62  transmits the rotation through claw  67  to claw  65 . A rotation of the dose setting knob is hence transmitted to the hollow shaft  50  and through the hollow shaft to the nut  40 . 
         [0091]    The claws  65  and  67  allow an axial movement of hollow shaft  50  and extension  62  with respect to each other due to the presence of a gap. A shoulder  71  is provided at the second claw  67  on the side of the dose setting knob. The extension  62  is conical beyond the shoulder. On the side of the dose setting knob the shoulder  71  is provided with a spur gearing  70 . 
         [0092]    An infeed jacket  66  is shifted over the extension  62 . The infeed jacket  66  has two sides: on the side of the cap  18  and one on the side of the dose setting knob  69 . A spur gearing  72  is provided on the side of the cap  18  the spur gearing engaging with the spur gearing  70  of the shoulder  71 . 
         [0093]    Four angularly symmetrical guiding rails  74  are provided along the outside of the infeed jacket  66 . A ring  76  on the side of the cap connects the guiding rails  74  with the infeed jacket  66 . The ring  76  is provided with a tooth shaped wave track  78  on the opposite side. The tooth shaped wave track  78  is interrupted by the guiding rails  74 . On the side of the dose setting knob  69  the end of the guiding rails  74  is provided with a saw tooth shape. 
         [0094]    The dose setting knob end of the infeed jacket  66  is provided with a first tooth shaped structure  80  cooperating with a second tooth shaped structure  82  of a push jacket  68 . The push jacket  68  is also coaxially arranged on the extension  62 . At its cap end the push jacket  68  is provided with projections  84  on the outside. 
         [0095]    A guiding bushing  86  is rotatably beared in the back portion  16  of the housing. Therefore, the guiding bushing  86  is provided with a brim  88  on its outside. Corresponding to the brim  88  a radial groove  90  is provided in the back portion  16  of the housing. The brim and the radial grove  90  form a bush bearing. In an alternative embodiment which is not shown the guiding bushing  86  is not rotatable. 
         [0096]    The guiding bushing  86  is provided with guiding grooves  92 . The numbers of guiding grooves  92  correspond to the numbers of projections  84  of the push jacket  68  and the numbers of guiding rails  74  of the infeed jacket  66 . The push jacket  68  is axially movable in the guiding bushing  86 . A dose setting knob end of the guiding bushing is provided with a block  94  for the infeed jacket  66 . The block  94  is shown in  FIG. 1 . 
         [0097]    The cap end of the guiding bushing  86  is provided with a saw tooth shaped spur gearing  98  that correspond with the saw tooth shaped ends of the infeed jacket  66 . The saw teeth  98  of the guiding bushing  86  are formed in such a way that a guiding groove  92  is arranged after every second steep flank. 
         [0098]    The above mentioned release spring  96  is arranged axially between the hollow shaft  50  and the infeed jacket  66 . The release spring  96  is shown in  FIG. 1 . The release spring pushes both claws  65  and  67  apart. 
         [0099]    The spring constant of the release spring  96  is larger than the spring constant of the pressure spring  53 . Hence, in first approximation the pressure spring  53  is compressed first before the release spring  96 . 
         [0100]    The release spring  96  and the pressure spring  53  load the infeed jacket  66  with a force acting in the direction of the dose setting knob  69 . Thereby, the infeed jacket  66  is pushed against the guiding bushing  86 . 
         [0101]    If the infeed jacket  66  engages with its guiding rails  74  in the guiding grooves  92  the infeed jacket  66  moves by the spring force of the pressure spring  53  in the direction of the end portion  12 . Together with the infeed jacket  66  the push jacket  68  moves in the guiding bushing  86  until the projections  84  of the push jacket  68  reach the block  94  of the guiding grooves  92  in the guiding bushing  86 . This defines the first position of the infeed jacket  66 . The dose setting knob  69  is now accessible and can be rotated and otherwise operated. 
         [0102]    By pushing the dose setting knob  69  at first the pressure spring  53  is compressed. The push jacket  68  moves in the direction of the cap  18 . Thereby, the infeed jacket  66 , the extension  62  and the hollow shaft  50  are also moved in that direction. When the conducting tube  56  reaches the metal contacts at the bearing sleeve  48 , the switch is closed. 
         [0103]    Thereby, the administered insulin dosage is saved. Additionally, a time stamp is generated and saved in a memory. The insulin pen is in an energy saving mode. 
         [0104]    The release spring  96  is compressed by further pressure on the dose setting knob  69 . Thereby, the distance between the claws  65  and  67  is reduced. When the guiding rails  74  of the infeed jacket  66  are not guided by the guiding grooves  92  of the guiding bushing  86  the infeed jacket  66  is turned further one saw tooth of the guiding bushing  86  by the spur gearing between push jacket  68  and infeed jacket  66 . 
         [0105]    There are no guiding grooves corresponding to the guiding rails  74  of the infeed jacket  66 . If the dose setting knob  69  is not pushed anymore the release spring relaxes and pushes the infeed jacket  66  against the guiding bushing  86 . The infeed jacket  66  is locked in that position. 
         [0106]    In this position the dose setting knob  69  is hidden in the housing of the assembly. The dose setting knob  69  is secured against accidental actuation. 
         [0107]    With repeated pushing of the dose setting knob  69  in the direction of the cap  18  the release spring is compressed. The push jacket  68  pushes the infeed jacket  66  in the direction of the cap  18 . When the guiding rails  74  of the infeed jacket  66  are shoved over the steep edge of the saw tooth shaped spur gear  98  of the guiding bushing  86  by effect of the spur gear between push jacket  68  and infeed jacket  66  the infeed jacket  66  is rotated further one saw tooth of the guiding bushing  86 . 
         [0108]    The guiding rails of the infeed jacket  66  now accompany corresponding guiding grooves  74  of the guiding bushing  86 . Upon releasing the dose setting knob  69  the infeed jacket  66  moves in the direction of the end portion  12 . Thereby, the dose setting knob  69  moves out of the end portion  12 . The dose setting knob is now accessible and can be rotated and can be otherwise operated. 
         [0109]    A display  100  is provided at the assembly  10 . The casing is also provided with a clip  102 . This serves for the attachment of the assembly to a pocket or the like. Furthermore, a color coding is provided at the back portion  16  of the housing. This allows for a color coding of different insulin. 
         [0110]    A switch  106  activates the assembly  10  upon first initiation. It is understood that the first activation can also be conducted by inserting batteries. The batteries are exchangeable. 
         [0111]    The application assembly  10  is switched on and off by operating the dose setting knob  69 . If the application assembly is switched on the last applied insulin dosage and the point in time of the last application are displayed on the display  100 . A timer  110  shown in  FIG. 4  determines the time. A processor  112  then calculates the time of the day and the date. At predefined times the contents of the memory  114  are sent by a radio circuit. The transmitted signal can also be manually triggered. A switch  107  is provided for this purpose. 
         [0112]    In  FIG. 4   a  schematic of a network is shown. The network comprises an application assembly  10 , a base station  120  and a data processing unit  130 . 
         [0113]    The application assembly comprises the memory  114 , a sending and receiving arrangement  116  and a timer  110 . The application assembly  10  can communicate with the base station  120 . Therefore, a sending and receiving arrangement  122  is provided in the base station. 
         [0114]    The communication is bi-directionally established by radio frequencies, for example in the frequency range of 868 MHz. Upon insertion of the batteries the application assembly  10  searches for the base station  120 . Radio signals are emitted for this purpose. 
         [0115]    The base station  120  receives this signal and sends a signal to the application assembly  10 . Then, the timer  110  inside the application assembly  10  is started. The base station  120  also transmits the next communication time to the application assembly  10 . The application assembly then sends a signal to the base station  120  at predefined times. 
         [0116]    If the application assembly does not receive a signal from the base station within a certain time interval the application assembly stops broadcasting. Thereby, the battery of the application assembly  10  is not unnecessarily used up. 
         [0117]    If communication with the base station is established the application assembly  10  broadcasts the saved, applied insulin dosages with the corresponding timestamp. The base station  120  transmits the data received from the application assembly  10  to a data processing unit  130 . 
         [0118]    This transmission is carried out by a modem  124  provided in the base station  120 . In the present embodiment the modem uses the mobile network standard GSM. The base station  120  logs in the data processing unit via modem  124 . Subsequently, data are exchanged. The data in the data processing unit are accessible by a web interface. The web interface allows for settings at the base station or at the application assembly. 
         [0119]    An alternative embodiment of an application assembly generally denoted with numeral  300  is shown in  FIG. 7 . 
         [0120]    As in the previous embodiment the application assembly  300  is provided with a casing  312  with a cap  318  and a cartridge  320 , which is separated into a front portion of the casing  314  and a back portion of the casing  316 . The cartridge  320  is provided with a membrane  322  and a plug  324 . The cartridge  320  is held in an adapter assembly to adapt cartridges of different suppliers and dimensions to the present application assembly. A switch  490  detects whether an adapter assembly is inserted. 
         [0121]    The adapter assembly of the present embodiment comprises, as in the previous embodiment, a casing  328 , a threaded rod  338 , a disk  334  and a disk  340 , as well as an additional plunger  339 . The components of the adapter assembly are separately shown in  FIG. 8  in greater detail. The functionality of the adapter assembly does not essentially differ from the adapter assembly of the above described embodiment. The cap side of the plunger  339  is clipped to the threaded rod  338 . Therefore, the pressure is evenly distributed on the plug  324 . 
         [0122]    The dose setting knob end of the casing  324  is closed and is provided with a central aperture  330 . The aperture  330  is a circular opening with two inwardly rising radial projections. The profile of the threaded rod is provided with two corresponding depressions  329  and  331 . 
         [0123]    The disk  334  is provided with an oval opening  336  adapted to the cross section of the threaded rod. The edge of the opening  336  is partially provided with radial slits. Thereby, small concentric tongues  337  are formed of elastic sheet metal. The threaded rod  338  extends through the aperture  330 . 
         [0124]    The nut  340  follows the rotation of the dose setting knob  402  by a mechanical design described below. The cap side of the nut  340  is provided with a saw tooth shaped spur gear  341 . The spur gear  341  of the nut  340  engages with a corresponding spur gear  343  at the casing  328 . The slope of the saw teeth correspond to the slope of the thread of the threaded rod  338 . Thereby, it is ensured that only predefined units can be administered. 
         [0125]    The functional principle of the dosing is illustrated in  FIGS. 9(   a - c ). Before application both toothings are on top of each other. This is shown in  FIG. 9   a . If the nut  340  on the threaded rod is rotated the toothing  341  is shifted against the toothing  343 . The inclined edges of the toothing are still in touch. A force F that acts in the marked direction does not lead to an axial movement of the threaded rod. This can be seen in  FIG. 9   b . When the nut is shifted so far that the steep flanks of the toothing face each other the threaded rod can be moved in the direction of the cap by the marked force F. This is shown in  FIG. 9   c . The mechanism improves the accuracy of applications. 
         [0126]    The cap  318  is formed by a tube  350  with an essentially triangular cross section. This can be well seen in  FIG. 10   a . One end of the triangular tube  350  is closed by an end piece  352 . The front portion of the casing  314  serves as reception for the casing  328  of the adapter assembly  327 . The plunger  339  and the disk  334  are arranged in the casing  328 . The nut  340  and the threaded rod  338  extend into the back portion of the casing  316 . This can be seen in  FIG. 7 . The portion of the casing  316  comprises an elongated corpus  356  also having an essentially triangular cross section. This is shown in  FIG. 10   b . An intermediate piece  354  is located between the portion of the casing  314  and the corpus  356 . 
         [0127]    The intermediate piece  354  is provided with a bayonet coupling having the front portion of the casing  314  attached thereto. The intermediate piece  354  is provided with depressions  360  that engage with projections  332  in the casing  328 . The casing  328  is hence secured against rotation. 
         [0128]    A display and control panel  372  is fitted into the corpus  356 . The display and control panel  372  comprises a display window  374  and an operator panel  376 . A control sensor  380  which is addressed by the control panel  376  is located on a display circuit board  378 . Furthermore, a display  382  is located on the display circuit board  378 . 
         [0129]    A slit  362  for a battery holder  364  is provided at the corpus  356 . The battery holder  364  holds batteries or accumulators  366 ,  368  and  370  providing the application assembly  300  with electricity. The battery holder  364  holds the batteries  366 ,  368  and  370  in a battery compartment  384 . The battery compartment  384  is also provided in corpus  356 . 
         [0130]    A contact strip  386  connects the plus terminal of the batteries  366 ,  368  and  370  with the display circuit board  378 . The negative terminal of the batteries  366 ,  368  and  370  is connected to the display circuit board  378  via a sheet metal tongue  388 . 
         [0131]    A clip  390  is attached to the battery compartment  384  by a screw  392 . A clip cover  394  covers the screw  392 . 
         [0132]    A sensor circuit board  396  is electrically connected to the display circuit board  378 . Two magnetic sensors  397  and  398  are provided on the sensor circuit board  396 . An ON-sensor  399  is also provided on the circuit board. A knob enclosure  400  forms one end of the corpus  356 . 
         [0133]    The actual mechanical design of the application assembly comprises, from the right to the left: the dose setting knob  402  the knob enclosure  400 , a hat element  404 , a crown  406 , a counter crown,  408 , a balance spring  410 , a securing ring  412 , a block  414 , a ring magnet,  416 , a pressure spring  418 , a shaft  420 , a coupling element  422  and a latch element  424 . The interaction of the components is described below with reference to  FIGS. 11   a  and  11   b.    
         [0134]    The coupling element  422  connects the nut  340  to the shaft  420 . The coupling element  422  is rotationally symmetrical about a longitudinal axis of the application assembly  300 . The coupling element  422  is pivotably mounted in a space formed by the display- and control panel  372  and the battery compartment  384 . 
         [0135]    The coupling element  422  is provided with a longitudinal bore hole  426 . The inner wall of the coupling element  422  is provided with guiding grooves  428 . The attachments  342  provided on the nut  340  are guided in the guiding grooves  428 . The nut  340  is movable along the axis of the coupling element  422  and follows the rotation of the coupling element  422 . As the nut  340  is located on the threaded rod  388  it  340  moves in the axial direction of the coupling element  422 . 
         [0136]    A shaft  420  is guided in the coupling element  422 . Radial, outwardly projecting noses  430  are provided with at the end of the shaft hidden in the coupling element  422 , the noses cooperating with the guiding grooves  428  of the coupling  422 . The shaft  420  is movable in an axial direction along the guiding grooves  428 . The coupling  422  is charged with the spring force of a pressure spring  418 . On the side of the dose setting knob the shaft  420  has a reduced diameter for receiving a securing ring  412 . 
         [0137]    The coupling element is provided with a circumferentially thickened portion  431 . On the cap side of the thickened portion  431   a  saw tooth profile  432  is provided. The saw tooth profile  432  engages with a corresponding profile  343  of the latch element  424 . 
         [0138]    Upon, for example, clockwise rotation of the shaft  420  the saw teeth disabling and the coupling element  422  moves against the spring force of the pressure spring  418 . As soon as the steep flanks of the saw teeth face each other the pressure spring  418  relaxes and shifts the coupling element  422  against the latch element  424 . 
         [0139]    This movement is audible as well as tangible. The latch element  424  and the coupling element  422  form an acoustic and haptic feedback for setting a selected dosage by rotation. 
         [0140]    In order to provide a feedback upon rotation in the opposite direction, i.e. in this example counter-clockwise, the latch element is provided with another spur gear  436  on the opposite side. This is directed in the opposite direction and engages with a saw tooth profile  438  that is provided on the dose setting knob side of the intermediate portion  354 . Upon rotation in a clockwise direction the teeth of the spur gear  436  and the saw tooth profile  438  jam. The coupling element  422  and the latch element rotate with respect to each other and provide the feedback. Upon a rotation in a counter-clockwise direction the effect reverts. Latch element  424  and coupling element  422  jam up and the latch element moves with respect to the intermediate piece  354  whereby the respective toothing provide the acoustic and haptic feedback. 
         [0141]    Six bar magnets  440 ,  442 ,  444 ,  446 ,  448  and  450  are arranged along the circumference of the coupling element  422 . The orientation is chosen in such a way that a north and a south pole are alternatively revolving. A magnetic field is formed between each neighboring pole running from north to south pole. 
         [0142]    The orientation of the magnetic fields is detected and processed by to magnetic sensors  397  and  398  on the sensor circuit board  396 . The principle is shown in  FIGS. 12(   a - d ).  FIG. 12  shows a cross section of the magnets. Magnetic sensors  397  and  398  are located on the sensor circuit board  396 . The magnetic sensors  397  and  398  react on the penetration direction of a magnetic field penetrating the sensor surface. The signals generated by the magnetic sensors are discussed below on the basis of a clockwise rotation. 
         [0143]    In  FIG. 12   b  the magnetic sensor  397  is penetrated by a magnetic field between magnets  440  and  442 . The magnetic field is oriented from top to bottom in the Figure. The magnetic sensor detects a signal that is assigned to zero. The magnetic sensor  398  is penetrated by a magnetic field between the magnets  450  and  440 . In the drawing the magnetic field is oriented from bottom to top. The magnetic sensor detects a signal that is assigned to one. 
         [0144]    In  FIG. 12   c  the magnetic fields are undefined. The sensors keep the previous signal. Upon further clockwise rotation the directions of the magnetic field in both magnetic sensors  397  and  398  are reversed. This is shown in  FIG. 12   d.    
         [0145]    The output signals of the magnetic sensors  397  and  398  change. The orientation of the magnetic fields and hence their output signal changes with every rotation by 60°. The sequence of the changes are electronically processed and converted into adjusted units which then are displayed on the display  382 . For illustration the following table is shown: 
         [0000]    
       
         
               
               
               
               
             
           
               
                   
               
               
                   
                   
                 magnetic field 
                 output 
               
               
                 clockwise 
                 magnetic sensor 
                 direction 
                 signal 
               
               
                   
               
             
             
               
                 FIG. 12b 
                 magnetic sensor 
                 down 
                 0 
               
               
                   
                 397 
                   
                   
               
               
                   
                 magnetic sensor 
                 up 
                 1 
               
               
                   
                 398 
                   
                   
               
               
                 FIG. 12c 
                 magnetic sensor 
                   
                 0 
               
               
                   
                 397 
                   
                   
               
               
                   
                 magnetic sensor 
                   
                 1 
               
               
                   
                 398 
                   
                   
               
               
                 FIG. 12d 
                 magnetic sensor 
                 up 
                 0 
               
               
                   
                 397 
                   
                   
               
               
                   
                 magnetic sensor 
                 down 
                 1 
               
               
                   
                 398 
                   
                   
               
               
                 FIG. 12a 
                 magnetic sensor 
                   
                 0 
               
               
                   
                 397 
                   
                   
               
               
                   
                 magnetic sensor 
                   
                 1 
               
               
                   
                 398 
               
               
                   
               
             
          
         
       
     
         [0146]    The counting in the other rotating direction operates likewise. It is possible to use Hall sensors. Contrary to mechanical parts for processing the adjusted dosage the components of the present embodiment do not wear off. Hence, the accuracy and the life time of the application assembly  300  are further improved. 
         [0147]    The pressure spring  418  is clamped between the coupling element  422  and the ring magnet  416 . The cap side of the block  414  is provided with a broadened edge  452  with the ring magnet  416  and dose setting knob sided a smaller end. A ledge  456  is formed between the smaller end  454  and the broadened end  452 . The smaller end  454  is hidden in the counter crown  408  up to the ledge  456 . 
         [0148]    The counter crown  408  is attached to the dose setting knob  402 . Guiding grooves  460  are provided in the counter crown  408 . Such grooves do not break through the cap end  462 . Corresponding guiding rails  464  of the shaft  420  run in the guiding grooves. The shaft  420  is biased by a balance spring  410  between shaft  420  and doses setting knob  402 . The securing ring  412  limits the path of the guiding rails  464  in the guiding grooves  460 . The balance spring  410  ensures that the nut  420  is reliably pressed against the casing  328 . 
         [0149]    The dose setting knob  402  can be hidden in the knob enclosure  400 . In the hidden position the pressure spring  418  is biased. In its extended position the pressure spring is relaxed. Thus, the shaft  420  is slightly pushed off the coupling element  422 . A gap appears between the nut  340  and the shaft  420 . 
         [0150]    Upon rotation of the dose setting knob  402  the counter crown  408  connected thereto is rotated. The rotation is transmitted onto the shaft  420  through the guiding grooves  460  and the guiding rails  464 . By a rotation of the dose setting knob  402  the shaft  420  is also rotated in a clockwise direction. Thereby, the nut  340  is moved in the coupling element  422  in the direction of the shaft  420 . The gap between the shaft  420  and the nut  340  is reduced. The gap between the casing  328  and the nut  340  is increased. 
         [0151]    By pressing the dose setting knob in the direction of the cap the shaft  420  is moved and the pressure spring  418  is compressed. The gap between shaft  420  and nut  340  is reduced. Upon continuous pressure on the shaft  420  the nut moves in the direction of the cap as soon as the shaft touches nut. As the nut  340  is attached to the threaded rod by the thread it is also moved. The movement ends, once the gap between nut  340  and casing  328  is closed. Only the pressure spring  418  is compressed thereafter. 
         [0152]    Thereby, the ring magnet  416  is moved until it triggers the ON sensor  399 . In the present embodiments the ON sensor comprises a reed contact. The ON sensor generates a signal indicating that insulin has been administered. It also serves for switching the application assembly  300  on and off. 
         [0153]    The crown  408  is provided with a tooth shaped structure  466  at its dose setting knob end  402 . Along the outside of the crown  408  four circumferential guiding rails  468  are provided. A ring shaped projection  470  interconnects the guiding rails  468  of the crown  408 . The dose setting knob side of the ring shaped projection is provided with a tooth shaped wave track. The tooth shaped wave track is broken by the guiding rails  468 . The dose setting knob end of the guiding rails  468  matches the tooth shaped structure  466 . 
         [0154]    A push sleeve  474  which is provided with a tooth shaped structure  476  is attached in the dose setting knob  402 . The tooth shaped structure  476  and the tooth shaped structure  466  form a spur gear. Projections  478  are provided at the outer wall of the push sleeve  474 . They correspond to the guiding rails  468  of the crown  408 . 
         [0155]    The hat element  404  is pivotably mounted in the back portion of the casing  316 . For this purpose the hat element  404  is provided with a circumferential brim on its outside. Corresponding to the brim a circular groove  482  is provided in the knob enclosure  400 . Brim and circular groove  482  form a bush bearing. 
         [0156]    The hat element is provided with guiding grooves  488 . The number of the guiding grooves  488  matches the number of projections  478  of the push sleeve  474  and the number of guiding rails  468  of the counter crown  408 . The push sleeve  474  is axially movable in the hat element  404 . 
         [0157]    The cap end of the hat element  404  with the brim is provided with a saw tooth shaped spur gear  486  on the inner edge that engages with the ends of the guiding rails  468 . The saw teeth of the spur gear  486  of the hat element  402  are designed in such a way that a guiding groove  488  is arranged after every second steep flank. 
         [0158]    The spring constant of the balance spring  410  is larger than the spring constant of the pressure spring  418 . 
         [0159]    In OFF mode of the application assembly  300  the dose setting knob  402  is hidden in the knob enclosure  400 . The dose setting knob  402  is secured against accidental actuation. A circumferential ledge on the inside of the crown  406  and a thickened portion provided at the end  462  of the counter crown prevent its slipping out of the dose setting knob  402 . 
         [0160]    For release the dose setting knob  402  is pushed in the direction of the cap. Thereby, the push sleeve  474  pushes the crown  406  so far in the direction of the cap that the guiding rails  468  of the crown  406  are pushed over the steep flank of the saw tooth shaped spur gear  486  of the hat element  404 . By effect of the spur gear between push sleeve  474  and crown  406  the crown  406  is turned further by one saw tooth of the hat element  404 . Now guiding rails  468  face corresponding guiding grooves of the hat element  404 . 
         [0161]    By releasing the dose setting knob  402  the crown  406  moves towards the knob enclosure  400  by means of the spring pressure of the pressure spring  418 . Thereby, the dose setting knob  402  moves out of the knob enclosure  400 . The dose setting knob is now accessible and can be rotated and actuated. 
         [0162]    After adjusting the dosage the crown  406  is pushed in the direction of the cap by pushing the dose setting knob  402 . Thereby, the shaft  420  is also moved. The shaft  420  actuates the nut  340  that transmits its movement to the threaded rod  338 . The threaded rod  338  pushes the plug of the cartridge to administer insulin. The ring magnet  416  moves towards the cap, whereby the administered insulin dosage is saved. A time stamp is generated. This time stamp is filed in a memory. The insulin pen is shifted into an energy saving mode where the display is turned off. 
         [0163]    As soon as the nut  340  touches the casing  328  the pressure spring  418  is further compressed upon pushing the dose setting knob  402  and the crown  406  moves further in the direction of the cap. When the guiding rails  468  of the crown  406  are not guided by the guiding grooves  488  of the hat element  404  anymore the crown is turned further by one saw tooth of the hat element  404  by effect of the spur gear between push sleeve  474  and crown  406 . There are no guiding grooves corresponding to the guiding rails  468  of the crown  406 . 
         [0164]    If the dose setting knob is not pushed anymore the pressure spring  418  relaxes and pushes the crown  406  against the hat element  404 . The crown  406  is locked. In this position the dose setting knob  402  is concealed in the casing of the application assembly  300 . The dose setting knob  402  is secured against accidental actuation. 
         [0165]    The application assembly  300  is provided with the same electronic options as the assembly  10 .