Abstract:
Method and machine for the preparation of pharmaceutical products according to which a container containing a liquid phase and a gaseous phase is connected to an aspiration circuit of a given amount of the liquid phase; a flow sensor being provided for detecting the passage of the liquid phase and of the gaseous phase along the aspiration circuit.

Description:
The present invention relates to a machine for the preparation of pharmaceutical products. 
     BACKGROUND OF THE INVENTION 
     A machine is known in the pharmaceutical product preparation field comprising a picking station adapted to receive at least one container, in particular a bottle or an infusion bag, containing a liquid phase and a gaseous phase; a conveying line for feeding the container into the picking station; and an aspiration circuit mounted in the picking station to pick a given amount of the liquid phase contained in the container. 
     Once the container has been overturned in order to arrange the gaseous phase over the liquid phase, the liquid phase is picked from the bottom of the container by means of a syringe. From the above, it derives that the known machines for the preparation of pharmaceutical products of the above-described type have few drawbacks mainly deriving from the fact that the picking station requires a gripping device capable of moving and/or holding the container in the overturned position and is thus relatively complex and costly. 
     SUMMARY OF THE INVENTION 
     It is an object of the present invention to provide a machine for the preparation of pharmaceutical products which is free from the above-described drawbacks and which is simple and cost-effective to be implemented. 
     According to the present invention, a machine for the preparation of pharmaceutical products is provided as claimed in the attached claims. 
     The present invention further relates to a method for the preparation of pharmaceutical products. 
     According to the present invention, a method for the preparation of pharmaceutical products is provided as claimed in the attached claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The present invention will now be described with reference to the accompanying drawings, which illustrate a non-limitative embodiment thereof, in which: 
         FIG. 1  is a diagrammatic perspective view, with parts removed for clarity, of a preferred embodiment of the machine according to the present invention; 
         FIG. 2  is a diagrammatic perspective view, with parts removed for clarity, of a first detail of the machine in  FIG. 1 ; 
         FIG. 3  is a diagrammatic perspective view, with parts removed for clarity, of a detail in  FIG. 2 ; 
         FIG. 4  is a diagrammatic perspective view, with parts removed for clarity, of a second detail of the machine in  FIG. 1 ; 
         FIG. 5  is a diagrammatic perspective view, with parts removed for clarity, of a third detail of the machine in  FIG. 1 ; 
         FIG. 6  is a diagrammatic perspective view, with parts removed for clarity, of a detail in  FIG. 5 ; 
         FIG. 7   a  is a diagrammatic perspective view, with parts removed for clarity, of a fourth detail of the machine in  FIG. 1 ; 
         FIG. 7   b  is a perspective view of a detail in  FIG. 7   a;    
         FIG. 8  is a schematic perspective view, with parts enlarged and parts removed for clarity, of a fifth detail of the machine in  FIG. 1 ; 
         FIG. 9  is a diagrammatic front view, with parts removed for clarity, of the detail in  FIG. 8 ; 
         FIG. 10  is a diagrammatic perspective view, with parts removed for clarity, of a sixth detail of the machine in  FIG. 1 ; 
         FIG. 11  is a diagrammatic perspective view, with parts removed for clarity, of a seventh detail of the machine in  FIG. 1 ; 
         FIG. 12  diagrammatically shows the operating principle of the detail in  FIG. 11 ; 
         FIG. 13  is a diagrammatic perspective view, with parts removed for clarity, of an eighth detail of the system in  FIG. 1  shown in two different operating positions; 
         FIG. 14  diagrammatically shows the operating principle of the detail in  FIG. 13 ; and 
         FIG. 15  is a diagrammatic perspective view, with parts removed for clarity, of a ninth detail of the machine in  FIG. 1 . 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     With reference to  FIG. 1 , numeral  1  indicates as a whole a machine for the preparation of pharmaceutical products comprising a substantially parallelepiped containment box-like frame  2  defining an inner chamber  3 , which is maintained in substantially sterile conditions by a pneumatic device of known type, shaped so as to feed a flow of sterile air through the chamber  3  and prevent the introduction of air from the external environment into the chamber  3 . 
     The chamber  3  accommodates therein a store  4  for storing syringes  5 ; a store  6  for storing bottles  7 ; an annular store  8  for storing infusion bags  9 ; and a robotized gripping and transporting device  10  of the syringes  5  and/or of the bottles  7 . 
     Each syringe  5  ( FIG. 3 ) has a longitudinal axis  11 , and comprises a cylinder  12  provided with an end flange  13  orthogonal to axis  11 , a needle (not shown) coupled to the cylinder  12 , a closing cap  14  mounted to protect the needle (not shown) from possible contaminations, and a piston  15 , which is slidingly engaged in the cylinder  12 , and is provided with an end head  16  perpendicular to axis  11 . 
     Each bag  9  is provided with an adapter member  17  of known type, which comprises two shaped jaws  18 , mobile between a clamping position and a releasing position of an upper edge of the bag  9 , and has a drawing pin  19  protruding upwards from one of the jaws  18  ( FIG. 5 ). 
     As shown in  FIGS. 1 ,  3 , and  4 , the device  10  is mounted within the store  8 , comprises a plurality of jointed arms  20  hinged to one another, and provided with a gripping arm  21 , which is mounted on the free end of the arms  20 , and is defined by two jaws  22  mobile between a clamping position and a releasing position of a syringe  5  or a bottle  7 . 
     With reference to  FIG. 2 , each store  4 ,  6  comprises two reciprocally parallel belt conveyors  23 , each of which extends in a substantially vertical direction A, faces the other conveyor  23 , and is looped about a pair of pulleys (not shown), which are coaxial with the pulleys (not shown) of the other conveyor  23 , and are mounted so as to intermittently rotate about respective rotation axis  24  parallel to one another and transversal to direction A. 
     Each store  4 ,  6  further comprises a plurality of transport cradles  25 , which extend between the conveyors  23 , are coupled to the conveyors  23  to oscillate, with respect to conveyors  23 , about respective axes  26  with fulcrum parallel to one another and to axes  24 , and which are uniformly distributed along the conveyors  23  themselves. 
     As shown in  FIG. 3 , each cradle  25  of the store  4  (hereinafter indicated by numeral  25   a ) has a substantially V-shaped transversal section, is arranged with an axis  27   a  thereof parallel to axes  24 ,  26 , is provided with a first slot  28  adapted to receive the flange  13  of a syringe  5  to guarantee the correct longitudinal positioning of the syringe  5  in the cradle  25   a , and further has a second slot  29  adapted to be engaged by the jaws  22  to allow the device  10  to pick the syringe  5  from the cradle  25   a  itself. 
     With reference to  FIG. 4 , each cradle  25  of the store  6  (hereinafter indicated by numeral  25   b ) has a substantially V-shaped transversal section, is arranged with a longitudinal axis thereof  27   b  inclined with respect to axis  24 ,  26 , and is provided with a slot  30 , which is obtained near the lower end of the cradle  25   b , allows to correctly position a bottle  7  with its concavity facing downwards, and allows the jaws  22  to pick the bottle  7  itself. 
     Each store  4 ,  6  extends through a loading station obtained through the frame  2  to allow the operator to load the syringes  5  or bottles  7  into the respective cradles  25   a ,  25   b , and through a single picking station, where the syringes  5  or the bottles  7  are picked from the respective cradles  25   a ,  25   b  by the device  10 , and for this reason the device  10  is relatively simple and cost-effective. Furthermore, the loading and unloading of the syringes  5  and of the bottles  7  in, and respectively from, the respective cradles  25   a ,  25   b  does not require the machine  1  to be stopped at all. 
     As shown in  FIGS. 5 and 6 , the store  8  comprises an annular, star-shaped wheel  31 , which extends about the device  10 , is mounted to rotate intermittently, with respect to the frame  2  and under the bias of an actuating device (known and not shown), about a substantially vertical rotation axis  32 , and has a plurality of pockets  33 , which are obtained along a peripheral edge of the wheel  31 , open radially outwards and are each adapted to receive and withhold a respective infusion bag  9 . 
     The pockets  33  are fed by the wheel  31  about axis  32  and along a circular path P extending through a loading and unloading station  34  of the bags  8  into, and respectively from, the store  8 , a weighing station  35  of the bags  9 , and a dosing station  36  for injecting a predetermined amount of pharmaceutical into the bags  9  themselves. 
     Each station  34 ,  35 ,  36  is provided with a linear transfer device  37  comprising a rectilinear guide  38  parallel to a horizontal direction  39  transversal to axis  32 , a slide  40  slidingly coupled to the guide  38  to perform rectilinear movements along the guide  38  in direction  39 , and a gripping fork  41  slidingly coupled to a slide  40  to move, with respect to the slide  40  and transversally to direction  39 , between a coupling position and a releasing position of the pin  19  of a respective adapter member  17 . 
     The device  37  from station  34  cooperates with a guide  42 , which is parallel to the respective guide  38 , is radially aligned with the pocket  33  arranged each time in station  34  to be slidingly engaged by the member  17  of a respective pocket  9 , and extends between the store  8  and an opening  43  obtained through the frame  2  to allow an operator to load the bags  9  on the guide  42  and to pick the bags  9  from the guide  42  itself. 
     With reference to  FIGS. 7   a  and  7   b , device  37  of station  35  cooperates with a weighing device  44  comprising a supporting mobile member  45 , which is coupled in known manner to a fixed part of the device  44  to move vertically under the weight of the bags  9 , is fork-shaped and defines a guide  46  radially aligned with the pocket  33  arranged on each time in station  35  to be slidingly engaged by the member  17  of a respective bag  9 . 
     The device  37  of station  36  cooperates with a guide (not shown), which is parallel to the respective guide  38 , is radially aligned with the pocket  33  arranged each time in station  36  to be slidingly engaged by the member  17  of a respective bag  9 , and is adapted to stop the bag  9  itself underneath a syringe  5 , which is transferred from the device  10  between the store  4  and a gripping and actuating assembly  47  of the syringe  5  itself. 
     As shown in  FIGS. 8 and 9 , the assembly  47  comprises a supporting block  48 , which is mounted to rotate about a horizontal rotation axis  49  transversal to axis  32 , and supports a gripping device  50  of the cylinder  12  and a gripping device  51  of the piston  15 . 
     The device  50  comprises two grippers  52 , which are reciprocally aligned in a direction  53 , the orientation of which depends on the position of the block  48  about axis  49 , and each comprise two respective jaws  54 , which are slidingly coupled to the block  48  to move, with respect to the block  48  itself, transversally to direction  53 , and are normally maintained in a clamping position of the cylinder  12  by respective springs  55  arranged between the block  48  and the jaws  54  and loaded so as to allow the axial movement of the syringe  5  through the grippers  52 . 
     The device  50  further comprises an intermediate gripper  56 , which extends between the grippers  52 , and comprises, in turn, two jaws  57  slidingly coupled to the block  48  to move with respect to the block  48  and under the bias of an actuating device (known and not shown), transversally to direction  53  between a clamping position and a releasing position of the cylinder  12  of a syringe  5 . 
     With regards to the above, it is worth noting that the jaws  57  are shaped so as to allow one of the jaws  57  to be inserted inside the other jaw  57  and also to clamp syringes  5  of relatively small diameter. 
     The device  51  comprises two jaws  58 , which are slidingly coupled to the block  48  to move with respect to the block  48  and under the bias of an actuating device (known and not shown), transversally to direction  53  between a clamping position and a releasing position of the head  16  of a syringe  5 , and are further slidingly coupled to the block  48  to perform rectilinear movements in direction  53  itself with respect to the block  48  and under the bias of an actuating device (known and not shown). Each jaw  58  has a plurality of grooves  59  (two grooves  59 , in the case in point) superimposed on one another in direction  53  to allow the device  51  to receive and withhold the heads  16  of syringes  5  of different size. 
     The operation of the assembly  47  will now be described starting from an instant in which the jaws  57  and the jaws  58  are arranged in their releasing positions and the syringe  5  is inserted by the device  10  within the jaws  54  against the bias of the springs  55 . 
     Once the syringe  5  is inserted within the grippers  52 , the jaws  58  are firstly closed over the head  16  and then lowered in direction  53  so as to move the syringe  5  through the grippers  52 , arrange the flange  13  in contact with the upper jaw  52  and, possibly, push the piston  15  fully into the cylinder  12 . 
     The operating sequence shown above allows to correctly position the syringe  5  in direction  53  and guarantees a correct, constant positioning of all syringe  5  regardless of the size thereof, of the initial position of the pistons  15  along the respective cylinders  12 , and of the axial, initial angular positions of the syringes  5  in the grippers  52 . 
     Finally, the jaws  57  are moved from the clamping position thereof of the syringe  5  within the assembly  47 , and the jaws  58  are moved to the clamping position thereof of the head  16  for controlling the movement of the piston  15  during the steps of aspirating and injecting of the pharmaceutical. 
     With reference to  FIG. 10 , the machine  1  further comprises a mixer device  60  for mixing a lyophilized or powder pharmaceutical and a diluent contained in a bottle  7  to one another. 
     The device  60  comprises a rotating plate  61 , which is mounted to alternatively rotate about a substantially horizontal rotation axis  62 , and is provided with a pair of jaws  63  coupled in known manner to the plate  61  to move, with respect to the plate  61 , transversally to the axis  62 , between a clamping position and a releasing position of a bottle  7 . Each jaw  63  is shaped so as to display, in the case in point, a pair of seats  64 , which cooperate with corresponding seats  64  of the other jaw  63  to allow the jaws  63  to withhold bottles  7  of different size. 
     As shown in  FIGS. 11 and 12 , the path P further extends through a picking station  65  of a predetermined amount of liquid from the bags  9 . The picking of the liquid of bag  9  is necessary when the total weight of the pharmaceutical and of the diluent contained in the bag  9  after having injected the pharmaceutical needs to be equal to a determined value lower than the weight of the diluent initially contained in the bag  9  itself alone. 
     The station  65  has an aspiration assembly  66  comprising a gripping device  67  adapted to receive and withhold an extraction needle  68 , which is connected to a hydraulic aspiration circuit  69 , is transferred by the device  10  in the device  67  after having been separated from a protective cap thereof (known and not shown), and is moved by the device  67  in direction A between a raised resting position, in which the needle  68  is arranged outside the bag  9 , and a lowered operating position, in which the needle  68  protrudes within the bag  9  over the diluent contained in the bag  9  itself. 
     The circuit  69  comprises an extraction pump  70 , a peristaltic pump in the case in point, having an inlet hydraulically connected to the needle  68  by means of a first pipe  71 , and an outlet hydraulically connected to a collection reservoir  72  of the diluent picked from the bags  9  by means of a second pipe  73 . 
     The bags  9  contain a determined amount of air, and for this reason the pipe  71  is provided with a flow sensor  74 , a capacitance sensor in the case in point, which allows to discriminate between the passage of air and of liquid along the pipe  71 , and thus correctly calculate the volume of liquid aspirated from the bags  9  by means of the pump  70 . In other words, the volume of liquid aspirated from the bags  9  is calculated only starting from the instant in which the sensor  74  detects the passage of liquid along the pipe  71 . 
     With reference to  FIGS. 13 and 14 , the machine  1  further comprises a feeding device  75  for feeding a diluent into a bottle  7  containing a lyophilized or powder pharmaceutical. 
     The device  75  comprises feeding assemblies  76 , two in the case in point, each of which comprises, in turn, a feeding reservoir  77  (e.g. a bag  9 ) for the diluent; a feeding needle  78  coupled to the frame  2  and hydraulically connected to the reservoir  77  by means of a pipe  79 ; and a pumping device defined, in the case in point, by a syringe  80 , which is connected to an intermediate point of the pipe  79 , and is actuated in known manner to aspirate a predetermined amount of diluent from the reservoir  77  and to feed the diluent itself into the bottle  7 . 
     The connection between the pipe  79  and the syringe  80  divides the pipe  79  into two segments  79   a ,  79   b , which are arranged in sequence and in this order between the reservoir  77  and the needle  78 , and which are provided with respective check valves  81   a ,  81   b , of which valve  81   a  avoids the flow back of diluent into segment  79   a  when diluent is fed to the needle  78 , and valve  81   b  avoids the flow back of diluent from segment  79   b  when the diluent is aspirated from the reservoir  77 . 
     The device  75  further comprises a collection reservoir  82 , which extends underneath the needles  78 , is coupled in known manner to the frame  2  to move with respect to the frame  2 , in direction A between a lowered resting position ( FIG. 13   b ) and an operating raised position ( FIG. 13   a ), and is hydraulically connected to a collection manifold  83  of the diluent. The reservoir  82  further displays a pair of tubes  84 , each of which protrudes upwards from a bottom wall of the reservoir  82 , is substantially coaxial to the respective needle  78 , and accommodates therein a protective cap  85  of the needle  78  itself arranged in the tube  84  with the concavity facing upwards. 
     In use, the reservoir  82  is moved, with the caps  85  of the needles  78 , to its lowered resting position to allow inserting two bottles  7  underneath the needles  78  and feeding the diluent into the bottles  7  themselves. 
     When they are extracted from the respective bottles  7  the bottles may have residues of the lyophilized or powder pharmaceutical, and for this reason at the end of each injection operating cycle of the feeding device  75 , the reservoir  82  is moved into its raised operating position so as to fit the caps  85  on the respective needles  78 , and the syringes  80  are actuated to allow to wash the needles  78  with the diluent contained in the reservoirs  77 . 
     The diluent fed through the needles  78  flows firstly into the respective caps  85  and thus into the reservoir  82  and into the manifold  83 . With this regard, it is worth noting that: 
     the amount of diluent used to wash the needles  78  also allows to wash the caps  85 ; 
     the caps  85  are, like the needles  78 , initially sterile and may therefore be used to wash the respective needles  78  at the end of each programmed injection operating cycles in a working session of the machine  1 ; and 
     the conclusion of the working session of the machine  1  requires only the replacement of needles  78  and of the respective caps  85  and does not require the sterilization of the reservoir  82 . 
     As shown in  FIG. 15 , the machine  1  is further provided with a collection device  86  of the processing waste (e.g. syringes  5 , bottle  7 , needles  78 , and caps  85 ) accommodated within the frame  2  underneath the store  8 , and comprising, in the case in point, two collection containers  87 , of which one (hereinafter indicated by numeral  87   a ) communicates with the chamber  3  by means of a pair of slides  88  and the other (hereinafter indicated by numeral  87   b ) communicates with the chamber  3  itself by means of one chute only  89 . 
     In use, the various processing waste is selectively fed by the device  10  to the various chutes  88 ,  89  and, thus, to the various containers  87   a ,  87   b , thus allowing to separate the processing waste. 
     The operation of the machine  1  is easily inferred from the description above and no further explanations are required.