Patent Document

[0001]    The present invention relates to a syringe, and in particular a syringe designed to be pre-filled then sterilized by steam autoclaving, as well as to an assembly comprising a package and such a syringe enclosed in this package. 
       BACKGROUND OF THE INVENTION 
       [0002]    A “pre-filled” syringe is a ready-to-use non-reusable product. This type of syringe is filled with the desired liquid and sterilized industrially by the pharmaceutical laboratory. Sterility of the container/contents assembly is achieved either by filling under aseptic conditions syringes whose components have been pre-sterilized, or by steam-sterilizing the container/contents assembly at the end. The present invention is concerned with the latter method of sterilization only. 
       DESCRIPTION OF THE PRIOR ART 
       [0003]    A pre-filled syringe of the prior art is shown in longitudinal cross section in  FIG. 1 . 
         [0004]    The syringe  100  comprises a cylindrical body  101  whose downstream end is closed by a wall  102  containing a “Luer” or “Luer-lock” type access  103  which in turn is sealed by a removable cap  104 . The upstream end of the body  101  is open to permit the forcible insertion of a rod  105 , forming a plunger, fitted with a piston  106  forming a seal, the latter generally comprising three sealing lips  107  defining two sealed annular chambers  108 ,  109 . 
         [0005]    The rod  105 /piston  106  assembly can slide leak-tightly inside the body  101  when pushed by for example a nurse, causing the liquid  110  contained inside the body  101  to exit toward a patient via the access  103 . 
         [0006]    Lastly, the upstream end of the body  101  comprises an annular bead  111  designed to act as an end stop to the rod  105 /piston  106  assembly and prevent it escaping from the body  101 . 
         [0007]    The industrial process of filling and sterilizing the syringe  100  is as follows: after putting on the cap  104 , filling, inserting the piston  106  and inserting and screwing the rod  105  onto the piston  106 , the syringe  100  is enclosed in a package (blister pack) comprising a thermoformed plastic part closed by a peel-off paper seal. This paper possesses the property of being permeable to water vapor but largely impassable to microorganisms. 
         [0008]    For steam sterilization to meet regulatory requirements (guaranteed sterility even in the event of heavy initial contamination), it must be carried out at a temperature of at least 121° C. for at least 15 minutes in so-called “wet” heat, which means that all parts requiring sterilization must be in contact with the steam, whether the steam arrives from the autoclave chamber after passing through the paper seal of the package, or whether it is from the vaporized contents of the syringe. 
         [0009]    However, the annular chambers  108 ,  109  formed between the lips  107  of the piston  106  are sealed off and are not therefore accessible to the steam. Sterilization will therefore be by “dry” heat. As a result, in order to sterilize these annular chambers, the sterilization period must be much longer than in “wet” heat (about 60 minutes instead of 15 minutes). This extended sterilization cycle causes three major problems: 
         [0010]    the production cost is much higher;
       there is increased breakdown of the material of the syringe body, increasing the risk of release of breakdown products (plastic additives or components of the glass such as aluminum) in the liquid  110 ;   it is impossible to sterilize certain active principles at 121° C. for 60 minutes because they would suffer unacceptable breakdown.       
 
         [0013]    It is an object of the present invention to overcome the above problems by simple means without greatly increasing the cost of the syringe. 
       SUMMARY OF THE INVENTION 
       [0014]    To this end, and in accordance with a first aspect, the invention relates to a syringe comprising:
       a body comprising a generally cylindrical side wall having an open upstream end in the vicinity of which an inward annular bead is formed, and a downstream end closed by a transverse wall containing an orifice;   a rod with a piston at one end forming a seal and possessing at least two annular sealing lips between which at least one annular chamber is defined, said rod being designed to be inserted into and slid along the inside of the body.       
 
         [0017]    An inner chamber designed to be at least partly filled with contents is then defined between the piston and the transverse wall of the body. 
         [0018]    In accordance with a general definition of the invention, the syringe also comprises means of communication formed in the body of the syringe and designed to place said annular chamber or chambers of the piston in communication with the outside of the body or with the inner chamber of the body, when the piston is inside the body and in contact with the annular bead. 
         [0019]    In practice, in the storage position (in other words when the syringe is pre-filled and is at storage temperature), the means of communication are situated upstream of the piston and there is no risk to the integrity of the contents of the inner chamber of the syringe body. 
         [0020]    During sterilization, the piston is in contact with the bead because of the pressure inside the body due to the syringe contents entering the vapor phase. The means of communication allow the steam to gain access to the annular chambers of the piston, either entering from outside the body (meaning from the chamber of the autoclave in which sterilization is being carried out) or from inside the body itself, in other words from contents that have entered the vapor phase. Of course, one chamber cannot be in communication at the same time with the outside of the body and with the inner chamber if the integrity of the inner chamber is not to be put at risk. 
         [0021]    The invention therefore enables sterilization by wet heat between the lips of the syringe piston, and as a result greatly reduces the amount of heat required for sterilization. 
         [0022]    Advantageously, the means of communication are also designed to place at least one region of the outside face of at least one sealing lip in communication with the outside of the body or with the inner chamber of the body, when the piston is in contact with the annular bead, while at least one other sealing lip continues, when the piston is in this position, to seal off the inner chamber of the body. 
         [0023]    The expression “integrity of the inner chamber” here means that no product has entered said inner chamber and none of the contents have leaked out of the body of the syringe (the contents may however reach the annular chambers of the piston). 
         [0024]    Throughout the description, the terms “upstream” and “downstream” will be used with reference to the direction of flow of the contents on their way out of the syringe, when the syringe is in use. 
         [0025]    In a first embodiment, the means of communication comprise at least one groove formed approximately axially in the side wall of the cylindrical body, on its inside face, which groove leads out of the body at the upstream end of the body and extends as far as a downstream end situated, when the piston is in contact with the inward annular bead, upstream of the downstream sealing lip and downstream of that sealing lip which is situated immediately upstream of the downstream sealing lip, the radial depth of the groove being great enough to locally break the seal between the outside face of at least the upstream sealing lip and the inside face of the side wall of the body. 
         [0026]    In a second embodiment, the means of communication comprise at least one orifice formed in the side wall of the body and designed to place the annular chamber or chambers of the piston in communication with the outside of the body when the piston is in contact with the annular bead, the downstream edge of said orifice being situated, when the piston is in contact with the inward annular bead, upstream of the downstream sealing lip and downstream of that sealing lip which is situated immediately upstream of the downstream sealing lip. 
         [0027]    In a third embodiment, the means of communication comprise at least one slot formed in the side wall of the cylindrical body, in its inside face, said slot extending between:
       an upstream end situated, when the piston is in contact with the inward annular bead, downstream of the upstream sealing lip and upstream of that sealing lip which is situated immediately downstream of the upstream sealing lip;   and a downstream end situated, when the piston is in contact with the inward annular bead, downstream of the downstream sealing lip;       
 
         [0030]    the axial length of the slot being less than the total axial length of the piston, and the radial depth of the slot being great enough to locally break the seal between the outside face of at least the downstream sealing lip and the inside face of the side wall of the body. 
         [0031]    The slot may for example be annular, of the same axis as the cylindrical side wall of the body. 
         [0032]    In one possible embodiment, the piston possesses three annular sealing lips defining two separate annular chambers, the means of communication being designed to place each of the annular chambers in communication with the outside of the body or with the inner chamber of the body when the piston is inside the body and in contact with the annular bead. 
         [0033]    Lastly, in accordance with a second aspect, the invention relates to an assembly comprising on the one hand an essentially bacteria-proof package, of which at least a part is water vapor-permeable, and on the other hand a syringe as described above, said syringe being enclosed in said package and its inner chamber at least partly filled with contents. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0034]    There now follows a description of a number of possible embodiments of the invention, as non-restrictive examples, with reference to the accompanying figures: 
           [0035]      FIG. 1  is a longitudinal section through a prior art syringe; 
           [0036]      FIGS. 2 and 3  are partial views in longitudinal section of a pre-filled syringe in a first embodiment of the invention, during storage and during sterilization, respectively; 
           [0037]      FIGS. 4 and 5  are views similar to  FIGS. 2 and 3 , showing a second embodiment; and 
           [0038]      FIGS. 6 and 7  are views similar to  FIGS. 2 and 3 , showing a third embodiment, in which the body of the syringe is shown in its entirety. 
       
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0039]    A syringe  1  comprises in the first place a body  2  comprising a generally cylindrical side wall  3  of axis  4 . The side wall  3  has an upstream end which is open and a downstream end which is closed by a transverse wall  5  containing an orifice  6  and extended by a conical nozzle  7  of the “Luer” or “Luer-lock” type. 
         [0040]    At its upstream end, the body has both a collar  8  for a nurse to press against with the fingers, and an inward annular bead  9 . 
         [0041]    The syringe  1  also comprises a rod  10  forming a plunger, at the downstream end of which is a piston  11 . The piston  11  possesses three annular sealing lips, namely an upstream lip  12 , an intermediate lip  13  and a downstream lip  14 , designed to be in contact with the inside face  15  of the side wall  3  of the body  2 . An annular chamber is defined between each two successive lips. In the embodiment illustrated, the piston  11  therefore has two annular chambers  16 ,  17 . 
         [0042]    The syringe  1  (body and rod) is here made of plastic, but it could be of glass. 
         [0043]    The rod  10  is designed to be inserted into the body  2  and slide along inside it leak-tightly when pushed by a user. The piston  11  and the inside of the body  2  are generally coated with silicone so that the piston slides easily. 
         [0044]    In this way an inner chamber is defined inside the body  2 , between the transverse wall  5  and the piston  11 . The inner chamber is filled with contents  18  which may be a medicinal solution, a solvent, etc. There is also usually a gas bubble  19  (air or nitrogen, for example, depending on the case) left inside this inner chamber. 
         [0045]    Lastly, the syringe  1  comprises a removable cap  20  for closing the orifice  6  formed in the transverse wall  5  of the body  2 . 
         [0046]    The syringe  1 , prefilled and equipped with the rod  10  and cap  20  is put in a package of the type described earlier. The whole is then placed in an autoclave for steam sterilization of the syringe  1 . 
         [0047]    According to the invention, means of communication are formed in the body  2  of the syringe  1  to allow the steam to sterilize the annular chambers  16 ,  17  of the piston  11 . 
         [0048]    In a first embodiment, shown in  FIGS. 2 and 3 , the means of communication consist of at least one groove  21  formed essentially axially in the side wall  3  of the body  2 , from the inside face  15 . The groove  21  preferably leads out of the body  2  at the upstream end of the body, interrupting the bead  9 , locally. In a variant, the groove or grooves  21  need not lead out of the body but could have an upstream end situated close to the downstream face  22  of the bead  9 . 
         [0049]    The groove  21 , or each groove  21  has the following features:
       the axial distance d between the downstream face  22  of the bead  9  and the downstream end of the groove  21  is such that:       
 
         [0000]        d&gt;h   12   +h   16   +h   13  and  d&lt;H−h   14              where
               H is the total axial length of piston  11 ,   h 12 , h 13  and h 14  are the axial lengths of the upstream  12 , intermediate  13  and downstream  14  sealing lips, respectively, of the piston  11 ,   h 16  is the axial length of the upstream annular chamber  16  of the piston  11 ;   
                   the radial depth p of the groove  21  is great enough to locally break the seal between the outer face of the upstream  12  and intermediate  13  sealing lips and the inside face  15  of the side wall  3  of the body  2 .         
         [0056]      FIG. 2  shows the syringe  1  in the storage position (syringe  1  at room temperature, for example in its package). The capacity of the body  2  is adapted to suit the desired volume of the contents  18  so that, in this position, the piston  11  is situated downstream of the groove  21 . In this way the contents  18  (in the liquid phase) of the syringe  1  are isolated by the three lips  12 ,  13 ,  14  of the piston  11 . The chambers  16  and  17  are sealed off and the groove  21  has no function. 
         [0057]    At the start of the sterilization cycle, the syringe  1  in its package is placed in the autoclave chamber, at room temperature, and autoclave pressure is established. The contents  18  of the syringe are in the liquid phase, so there is no pressure on the piston  11  to push it out of body  2  of the syringe  1 . In any case, the pressure in the autoclave chamber acts on the rod  10  and tends to push the piston  11  into the body  2  of the syringe  1 . The piston  11  is therefore always in a position such as to isolate the contents  18 . 
         [0058]    The temperature in the autoclave chamber rises gradually to 121° C., with an absolute pressure of around 2 bar. The contents  18  of the syringe  1  now vaporize, thus generating pressure inside the body  2 . This pressure is proportional to the temperature of the steam, and also varies as a function of the amount of gas (the bubble  19 ) in the body  2  of the syringe  1 . 
         [0059]    When the pressure in the body  2  of the syringe  1  is generating a force greater than that exerted by the autoclave pressure on the rod  10 , added to the force required to make the piston  11  slide, the piston retreats until it contacts the bead  9  ( FIG. 3 ). The steam  23  present in the autoclave chamber will now enter the groove  21 . Given the dimensional relationships mentioned above, the steam  23  also passes into the annular chambers  16 ,  17 , thereby sterilizing these chambers with so-called wet heat. In this position, the contents  18  of the syringe  1  are sealed off by the upstream lip  14  of the piston  11 , because the groove  21  has sufficient length to enable the two chambers  16 ,  17  to communicate with the outside of the body  2 , and is sufficiently short for there to be no risk of contamination of the inner chamber. 
         [0060]    Clearly, the dimensions of the body  2  of the syringe  1  and the volume of the contents  18  are chosen so that, during sterilization, the piston  11  makes firm contact with the bead  9 , and is therefore positioned correctly relative to the groove  21 . Furthermore, the near incompressibility of the piston  11  ensures that the contents  18  remain sealed off because the upstream lip  14  stays at a distance from the groove  21 . 
         [0061]    At the end of the sterilization cycle (in the cooling phase), the pressure in the body  2  of the syringe  1  will gradually drop and the contents  18  of the syringe  1  will return to the liquid state. When the pressure in the autoclave chamber generates a force greater than that generated by the contents of the syringe  1  added to that necessary to make the piston  11  slide, the latter will move back along the body  2  of the syringe  1  to its initial position ( FIG. 2 ). 
         [0062]    In a second embodiment, shown in  FIGS. 4 and 5 , the means of communication consist of at least one orifice  24  formed in the side wall  3  of the body  2 . The orifice  24 , which is preferably circular and radial, has an upstream edge  25  and a downstream edge  26 : these are situated at distances d 25  and d 26 , respectively, from the downstream face  22  of the bead  9 , such that: 
         [0000]        d   25   &gt;h   12  and  d   25   &lt;h   12   +h   16    
         [0000]        d   26   &gt;h   12   +h   16   +h   13  and  d   26   &lt;H−h   14 . 
         [0063]    Once again the dimensions of the body  2  are adapted to the volume of the contents  18  so that, in the storage position ( FIG. 4 ), the piston  11  is at a distance from the orifice  24 , so that the seal of the inner chamber is not affected by the orifice  24 . However, the orifice  24  is designed to place the two annular chambers  16 ,  17  in communication with the outside of the body  2 , in order to allow steam  23  to enter during sterilization ( FIG. 5 ), when the piston  11  is in contact with the bead  9 . 
         [0064]    Finally, in a third embodiment, the means of communication are an annular slot  27  formed in the side wall  3  of the body  2  from the inside face  15 . This slot  27  has an upstream end  28  and a downstream end  29 , and has the following features:
       the axial distance d 28  between the downstream face  22  of the bead  9  and the upstream end  28  of the slot  27  is such that:       
 
         [0000]        d   28   &gt;h   12  and  d   28   &lt;h   12   +h   16 ;       the axial distance d 29  between the downstream face  22  of the bead  9  and the downstream end  29  of the slot  27  is such that: d 29 &gt;H;   the radial depth p′ of the slot  27  is great enough to locally break the seal between the outer face of the intermediate  13  and downstream  14  sealing lips and the inside face  15  of the side wall  3  of the body  2 ; and   the axial length of the slot (d 29 −d 28 ) is less than the total axial length H of the piston  11 .         
         [0069]    This last feature ensures that the inner chamber is sealed off from the outside of the body  2  of the syringe  1  whatever the position of the piston  11  in the body  2 , between the storage position and the position of contact with the bead  9 . 
         [0070]    In a variant the slot  27  may occupy only a fraction of the perimeter of the body  2 . 
         [0071]    As in the embodiments described above, the body  2  is designed on the basis of the volume of the contents  18  so that the piston  11  is situated at a distance from the slot  27  when in the storage position ( FIG. 6 ): the integrity of the inner chamber is therefore not affected by the slot  27 . 
         [0072]    During sterilization ( FIG. 7 ), the piston  11  is pushed against the bead  9 , and the slot  27  therefore places the inside of the body  2  in communication with the annular chambers  16 ,  17 . In this embodiment, the steam with which the annular chambers  16 ,  17  of the piston  11  are sterilized is formed by the contents  18 , in the gas phase, of the body  2  of the syringe  1 , rather than by steam from the autoclave chamber. One of the advantages of this embodiment is that it enables the downstream lip  14  of the piston  11  to be sterilized. 
         [0073]    Thus, by adding means of steam communication situated upstream of the piston when the syringe is in the storage position and surrounding the annular chambers of the piston during sterilization, the invention enables steam to enter between the lips of the piston while maintaining the isolation of the syringe contents from the steam present in the autoclave chamber. 
         [0074]    It goes without saying that the invention is not limited to the embodiments described above by way of examples but that on the contrary it encompasses all variants. In particular, the means of communication could take the form of a suitable combination of the three individual embodiments that have been described.

Technology Category: 1