FR2715311A1 - Syringe system for mixing two compounds - Google Patents

Abstract

The system for mixing two compounds, at least one of which is a liquid, consists of a syringe (12) with an injection tip (32), containing the first of the compounds, connected to a container (10) holding the second compound by a sleeve (14) which guides the injection end of the syringe between a first position in which it is retracted from the container and a second one in which its needle (60) pierces the cover (22) of the container, giving access to its contents. The sleeve has one end (28) shaped to fit over the container rim and its cover, and another (46) shaped to receive the injection end of the syringe and hold it in place by means of an inner sealing bush (48) and a stop collar (49). The sleeve also contains a needle guide (82) and a plug (80) to cover the tip of the needle prior to use.

Description

 The present invention relates to a syringe device allowing the mixing of two compounds and the injection of the mixture thus obtained.

 More specifically, the invention relates to a device which allows the storage in separate form of two compounds which must be mixed before their injection.

 It is known that there are, in particular in the medical field, products which must be stored separately and which must not be mixed until their injection into a patient, for example by subcutaneous, intravenous or intramuscular route. This is in particular the case of medicinal products which are prepared in lyophilized form, therefore in powder form, and which must be mixed with a solvent, for example physiological saline to allow their administration to the patient.

 In other cases, the two compounds to be mixed can be liquids, these liquids not being able to be kept for a long time in mixed form.

 The most frequently used solution is to store the powder in a separate container which is closed by a perforable waterproof membrane using a needle. Furthermore, using a syringe, a certain amount of solvent is taken from a second container and the desired amount of solvent is injected into the first container through the membrane. The whole is then mixed in the first container and using the same syringe is aspirated the mixture. The syringe is then ready to inject the medicine.

 The solution described above has many drawbacks: on the one hand, it requires the use of the container closed by the perforable membrane, the syringe and the second container containing the solvent which are separated. In addition, the manipulations required are relatively complex. On the other hand, the asepsis conditions are not always easy to respect during the various manipulations of the two components.

 It should also be taken into account that lyophilization systems preferably accept standard glass containers with a flat outer bottom. It is therefore interesting that the part of the syringe device intended to receive the product to be lyophilized has this shape. On the other hand, most of the current drugs are already available in this form and any modification of packaging would require a new marketing authorization with long and costly stability studies.

 An object of the present invention is to provide a syringe device allowing the storage of the two compounds in separate enclosures, the mixing of these compounds and their injection into a patient while preferably allowing the lyophilization of one of the two compounds. in a first compartment independently of the sterilization of the solvent in a second compartment under conditions as close as possible to those encountered during the lyophilization of a product in a standard bottle, the syringe device being generally presented under the form of a single assembly which is easy to handle and which ensures throughout its storage period the maintenance of very advanced asepsis of the various parts of the device liable to come into contact with the patient or the product to be injected.

To achieve this aim, the syringe device allowing the mixing of two compounds, at least the first of which is liquid, which comprises a syringe provided with an injection end, the syringe containing said first compound, is characterized in that it further includes:
a bottle provided with an opening and a stopper capable of sealingly closing the opening of said bottle, said stopper comprising a central perforable zone,
means for guiding in translation of the injection end of said syringe between a first recessed position, called storage, and a second depressed position, called active, said guide means comprising a first end opening out opposite the zone perforable from said stopper and a second end for receiving the injection end of said syringe, said second end comprising first sealing means between the body of said syringe and said guide means, and means for ensuring sufficient securing between said syringe and said guide means while allowing said translation; and
communication means to allow the perforation of said central area and the communication of the interior of said vial and the internal volume of said syringe when the injection end of said syringe is brought into its second position.

 Preferably, said first sealing means comprise an elastic seal mounted inside the guide means and cooperating with the external face of the body of the syringe. The face of said seal cooperating with the body of said syringe may preferably include at least two sealing lips.

 Preferably, said first end of the guide means comprises means for securing on the opening of said bottle.

 It is understood that, thanks to the provisions of the invention, there is a single assembly which comprises, on the one hand, the bottle containing the product, preferably lyophilized, and, on the other hand, the syringe which contains the solvent. However, the two are linked together by guide means which make the mixing operation easy. In addition, it is understood that the bottle is a standard type bottle used during conventional lyophilization operations since the guide means can only be put in place after lyophilization. In addition, thanks to the sealing means the needle is protected during storage against the risk of contamination.

 According to a first embodiment, the communication means comprise a needle mounted at the injection end of the syringe and the tip of which is capable of perforating the central zone of the stopper when the end of the syringe is brought into its second position.

 It is thus understood that the needle plays the dual role of allowing communication between the interior of the body of the syringe and the vial and that of the conventional injection needle once the syringe is separated from the vial.

Also preferably, the syringe device further comprises a needle guard which surrounds the needle over its entire length and which has a piercing end extending beyond the point of
The needle and which is removable with respect to said needle, whereby the perforation of the stopper of the bottle is carried out by the first end of the needle guard.

 According to a second embodiment of the invention, the communication means comprise a tubular piece disposed between the central stopper zone and the injection end of the syringe, said tubular piece having a first end capable of close the central zone of the stopper and a second end capable of piercing a perforable partition formed at the injection end of the syringe when the latter is brought into its second position.

 It is understood that, in this second embodiment, the tubular part has two perforating ends which perforate the stopper of the vial and the perforable partition of the syringe when the syringe is inserted into the guide means thus allowing mixing of the two compounds, the perforable partition is preferably itself a perforable plug closing off said syringe.

 It is the same when, inside the syringe, there is a cartridge equipped with a perforable cap.

 Preferably also, the guide means further comprise second sealing means capable of ensuring with the first sealing means confinement of the communication means inside said guide means.

 Preferably also, the guide means comprise between their first and second ends an orifice closed by an aseptic micro porous filter.

 The presence of this filter has a double advantage. On the one hand, it allows part of the air contained in the guide means to exit which greatly facilitates the replacement of the syringe in the guide means while maintaining during storage the interior of the means of guidance under severe aseptic conditions.

On the other hand, it makes it possible to proceed, through this filter, to the introduction of a sanitizing gas after the fixing of the guide means on the bottle.

 More preferably, the syringe device comprises a self-injecting device which is mounted on the syringe-guide piece assembly after this assembly has been detached from the vial. The auto-injector device comprises a support for the means for immobilizing in translation of said guide piece, first pushing means for causing the syringe to sink into said guide piece by a first predetermined distance and second pushing means for cause the syringe plunger to sink into the syringe body by a second predetermined distance while not modifying the position of the syringe body, said first end of the guide piece forming a bearing surface on the patient's body.

 It is understood that the action of the first pusher allows the needle to be pushed into the patient's body by a predetermined depth while the action of the second pusher allows the injection of the mixture.

 More preferably, the syringe device further comprises annular protection means surrounding a part of the body of said syringe to prevent manual access to the external face of said part of the syringe body, a first end of said protection means being adjacent to said first sealing means when said syringe occupies its first position in said guide means, the axial length í of the protection means between its first and its second end being at least equal to the travel 1 ′ of said syringe in said means guide between its first and its second position.

 According to another embodiment, the seal comprises temporary means for securing in translation with the body of said syringe when said syringe is moved between its first and its second position.

Other characteristics and advantages of the present invention will appear better on reading the following description of several embodiments of the invention given by way of nonlimiting examples. The description refers to the appended figures in which:
- Figure 1 is a longitudinal sectional view of a first embodiment of the syringe device in its storage position;
- Figure 2 is a view similar to that of Figure 1 showing the syringe device in a position allowing the mixing of the compounds;
- Figure 3 is a longitudinal sectional view of a second embodiment of the syringe device, the latter being in its storage position;
- Figure 4 is a view similar to that of Figure 3 showing the syringe device in the compound mixing position;
- Figure 5 is a longitudinal sectional view of a third embodiment of the syringe device;
- Figure 6 is a partial view in longitudinal section of a fourth embodiment of the syringe device comprising a modified type vial;
- Figures 7a and 7b show another alternative embodiment of the guide piece respectively in vertical section and in section along the plane BB of Figure 7a;
- Figures 8a to 8c show yet another alternative embodiment of the syringe device;
- Figures 9a and 9b show two alternative embodiments of a guide piece provided with a crimping capsule;
- Figure 9c shows a syringe device comprising a guide piece according to Figure 9b;
- Figures 10a to 10d illustrate the use of an auto-injector device in conjunction with the syringe device;
- Figures 11a to lic are similar to Figures 8a to 8c but show an alternative embodiment; and
- Figure 12 shows in vertical section another embodiment of the syringe device.

 Referring first to Figure 1, we will describe a first embodiment of the syringe device. This essentially consists of a bottle 10, a syringe 12 and a guide sleeve 14 mounted on the bottle 10. More specifically, the bottle 10 which is intended to receive a first compound to be mixed, referenced 16 , which is preferably a lyophilized compound, has an opening 18 which preferably ends with a flange 20. A plug 22 of standard type closes the opening 18. This plug is made of a perforable material and which can be made integral with sealingly the flange 20 of the bottle by means of an aluminum cap 23 which leaves the central part of the stopper free, this part being perforable.

 Preferably, the stopper 22 comprises a cylindrical body 24 which cooperates with the opening 18 of the bottle. This cylindrical body 24 has axial openings 26, such that when the stopper is partially engaged in the opening of the bottle, the passages 24 allow the circulation of gases during the lyophilization operation whereas, when the stopper is fully inserted , it achieves a perfect seal.

 The guide piece 14 preferably has a cylindrical shape and has a first end provided with a clipping flange 28 on the stopper 22 and the flange 20 of the bottle, thus ensuring a fastening at least in translation between the guide piece 14 and the bottle. The guide piece has a diameter slightly greater than that of the body 30 of the syringe 12. As is well known, the body of the syringe 30 ends in an injection end 32 on which is mounted a needle 34.

In the embodiment shown in FIG. 1, the needle is protected by a cap 36, the end 38 of which cooperates in leaktight manner with the injection end 32 of the syringe and the second end 40 of which is perforable and extended by a cylindrical washer 42 which cooperates with an annular groove 44 formed in the flange 28 for fixing the guide piece 14. Thus the end 40 of the protective cap 36 is immobilized in translation and pressed against the perforable part 22 of the plug of the bottle 10. In addition, the washer 42 having its periphery pinched between the periphery of the stopper of the bottle and the groove 44 tightly covers the perforable part of the stopper and seals this end of the guide piece 14. As it will be explained later, other methods of protecting the needle can be used. The open end 46 of the guide piece 14 is provided with an internal seal 48 which is calibrated so that it provides a seal between the guide piece 14 and the body 30 of the syringe allowing movement in translation of the syringe inside the guide piece 14 while maintaining
Sealing throughout the translation. To achieve this seal, the elastic seal is preferably in the form of a ring and preferably has on its internal face three sealing lips 49 '.

In addition, the length 1 of the ring in the direction of movement of the syringe is sufficient to ensure sufficient attachment between the syringe and the guide piece 14 while allowing the translational movement of the syringe relative to the guide piece under the force of a force applied to the syringe. The length 1 is for example equal to 1 cm. In addition, the length of the joint helps to maintain the guide part and the body of the syringe in coaxial positions during the translational movement of the latter. Preferably, the seal 48 defines a first retractable internal shoulder 49 which limits the insertion of the syringe into the guide part when the syringe device is stored.

As also shown in FIG. 1, there is preferably provided inside the guide piece 14 a second shoulder 50 which limits the possibility of driving the syringe 12 into the guide piece 14. The shoulder 50 is defined in such a way that, when the end of the syringe abuts thereon,
The end of the needle 34 has passed through the central part 22 of the stopper but only protrudes very slightly in the bottle 10 in order to limit as much as possible the volume lost in the bottle when it is desired to recover by suction, in the vertical position, using the needle, the mixture produced in the bottle. Finally, as is well known, the syringe 12 comprises a piston 52 mounted to slide in the body of the syringe. This piston 52 includes a thread 54 in which the control rod of the piston 52 can be fixed. In its storage position, the second compound to be mixed is placed inside the volume 56 of the body of the syringe 12.

 According to an alternative embodiment, the open end 46 of the guide piece 14 is extended by a flared frustoconical collar 51. The purpose of this collar is to protect the fingers of the operator who holds the guide piece during refitting. place the syringe in this room after injection to the patient. It goes without saying that the flange could be replaced by another shape protruding from the external face of the guide piece and capable of protecting the fingers of the operator placed on the side opposite to the end 46 in which is reintroduced the syringe after being used.

 According to another variant, the clip flange 28 of the guide piece forms the entire circumference of the stopper 22 and tightens the tight fixing of the periphery of the stopper 22 on the flange 20 of the bottle. This arrangement avoids the introduction of the metal cartridge 23 shown in Figures 1 and 2.

 It is also possible to provide that the plug 22 and the bottom 40 of the cap 36 of the needle are pre-perforated in their center.

This characteristic makes it possible to reduce the effort which must be applied to the body of the syringe for the end of the needle to pass through the cap and the stopper. In addition, this arrangement makes it possible to reduce the quantity of particles released from the stopper when the needle passes through it.

This therefore prevents these particles from being injected with the mixture.

However, tightening the stopper in the opening 18 of the bottle ensures prestressing of the material constituting the stopper. A plug is thus obtained which, put in place, is watertight while having a pre-perforation.

 Also preferably, the guide piece 14 is made of a synthetic material, for example polypropylene, allowing its sterilization by conventional techniques such as autoclaving, gamma radiation, etc.

 The use of the first embodiment of the syringe device shown in FIG. 1 is as follows: in a first step, the compound to be lyophilized is placed in the bottle 10 which is then devoid of the guide piece 14. The stopper 22 is placed in its semi-depressed position. When the lyophilization operation is complete, the plug 22 is fully pushed in and the aluminum capsule 24 is put in place. The syringe 12 containing the second liquid compound which has been previously sterilized with its protective cap is put in place independently 36 in the guide piece 14 then this assembly is fixed to the bottle by the cooperation of the flange of the guide piece 14 and the flange 20 of the bottle 10. The syringe device is then in its state shown in FIG. 1 and is stored in this position. Alternatively, the syringe can first be placed in the guide piece. The syringe is then filled with the liquid and the latter is closed with the piston 52. This assembly is sterilized and then fixed on the bottle 10. Optionally, this assembly is carried out under a laminar flow hood.

 When it is desired to inject the mixture of the lyophilized compound 16 with the liquid 56 contained in the syringe 12, the procedure is as follows: the body of the syringe 12 is pushed into the guide part 14 until 'so that the body of the syringe abuts on the shoulder 50. In this position, the cap 36 which is elastic has deformed and the sharp end of the needle 34 to perforate the bottom 40 of the cap 36 and the perforable part of the stopper 22 of the bottle. This is what is shown in Figure 2.

The needle 36 thus allows the communication of the interior of the body of the syringe 12 and the interior of the vial 10. It then suffices to mount the control rod in the piston 52 of the syringe and to cause I ' partial depression thereof to pass a suitable amount of liquid 56 inside the bottle 10 to produce the mixture of compounds 16 and 56. When the mixture is actually obtained in the bottle 10, the piston 52 is withdrawn to draw the mixture inside the body 30 of the syringe which is placed vertically. It is then ready for use. It then suffices to extract the syringe 12 from the guide piece 14. It is understood that during this operation the cap 36 of the needle 34 is held on the vial 10 by the guide piece 14. It is possible to provide that the needle which was used to perforate the stopper and to make the mixture is detachable from the body of the syringe. It can then be replaced by another needle to inject the mixture.

 Referring now to Figure 3, we will describe a second embodiment of the syringe device. In this second mode, the bottle 10 intended to receive the lyophilized compound 16 and its stopper 22 are identical to those of FIG. 1. They will not be described again. The same goes for the guide piece 14, the end 28 of which is fixed to the bottle 10. The difference consists in the fact that the needle 34 is replaced by a tubular piece 60 which has two perforating ends 62 and 64, the part 60 being mounted inside the guide part 14 between the injection end 32 of the syringe 12 and the stopper 22 of the vial 10. This tubular part 60 is held in the axial position of the guide part 14 by radiating fins 66 which cooperate with the internal wall of the guide piece 14. In addition, the injection end 32 of the syringe is provided with a perforable partition 70 which is therefore arranged opposite the end 62 of the tubular part 60.

 As a variant, the tubular part 60 could consist of a double needle between which a filter of suitable nature is interposed. It can also be provided that, during the extraction of the syringe from the guide piece 14, the assembly of the two needles is held in place at the injection end of the syringe.

 Alternatively, it is possible to interpose between the clipping part 28 of the guide piece and the fixing capsule 23 a seal, for example an O 'ring.

 To use the syringe device and to mix the compounds contained respectively in the body of the syringe and in the vial 10, the body of the syringe is pushed into the guide piece 14 until the body of the syringe syringe comes into abutment on the shoulder 50. As best shown in FIG. 4, in this position, the sharp ends 62 and 64 of the tubular part 60 respectively perforate the perforable partition 70 of the syringe and the central part of the plug 22 of the bottle. It can also be seen that, in this position, the end faces of the radiating guide fins 66 serve as a stop between the stopper 22 of the bottle and the perforable partition 70 of the syringe effectively ensuring the perforation of the partition 70 and of the stopper 22. In this position, it is possible to pass part of the liquid contained in the syringe 12 by acting on its piston 52. Once the mixture has been produced in the bottle 10, it suffices to exert traction on the piston 52 to draw the mixture into the body of the syringe. This same type of manipulation can be carried out with a cartridge prefilled with liquid or with a syringe equipped with a cartridge.

 To proceed with the injection, it suffices to extract the syringe 12 from the guide piece 14 and to put in place a suitable needle at the injection end 32 of the syringe.

 As a variant, provision may be made for the bottle to be separated from the guide piece 14 in order to inject the mixture, the latter remaining integral with the end of the syringe. For this it suffices to provide for the flange 28 for fixing the guide piece on the bottle a cutout which allows tearing thereof, either manually or by rotation of the guide piece relative to the bottle.

 In this case, in order to inject the mixture into the patient by the subcutaneous or intramuscular route, it is necessary to make an additional insertion of the syringe into the guide piece so that the tip of the needle actually protrudes out of the underside of the fixing flange, the latter being in contact with the patient's skin. To control this depression, it is advantageous to provide inside the guide piece an additional shoulder, the shoulder 50 being retractable under the effect of the depression of the syringe.

 FIG. 5 illustrates a third embodiment of the syringe device. According to this embodiment, the cap 36 of the needle is replaced by a preferably cylindrical perforable part 80 which is fixed in the end of the guide part 14, the tip of the needle 34 penetrating into the perforable part 80 This perforable part 80 can be pre-perforated as can be the bottom of the cap 36. To guide the needle during the positioning of the syringe in the part 14, a guide tube 82 is provided which is arranged according to the axis of the part 14 and which is integral with the latter by means of radiating fins such as 84. In this figure, there is also shown an additional internal shoulder 85 which makes it possible to limit the penetration of the syringe in the part 14 when the injection is carried out, in the case where the vial is detached from the guide part 14, the syringe remaining engaged in the guide part.

 Alternatively, it is possible to provide that the part of the guide part 14 surrounding the perforable part 80 has a reduced diameter relative to the current part of the part 14 so that the lateral face of the perforable part 80 is pinched tightly in this restriction thus ensuring sealing inside the guide piece 14 in addition to the seal 48. In addition, it is understood that, the perforable piece 80 being pressed against the part of the plug 22 which will be perforated by the needle, this part of the stopper is protected against the risk of contamination. In addition, the pressure thus applied to the plug 22 improves the quality of the drilling of the plug.

 It is understood that these second and third embodiments may include all the variants described in connection with the first embodiment and in particular the pre-perforation of the bottle cap, the protective flange of the guide piece, the fixing of the cap to the bottle using the clip flange and the presence of an internal shoulder in this part so that, after insertion of the needle, the end of the latter is substantially in the plane of the internal face of the stopper .

 Figure 6 shows a fourth embodiment of the syringe device which differs essentially from the previous ones by the constitution of the bottle 10 which bears the reference 10 'in this figure. The bottle 10 'has a body 90, preferably cylindrical, the bottom 92 of which is closed off by a perforable membrane 94, the periphery of which has a groove which cooperates with a bead 96 on the bottom of the bottle. The second end 98 of the bottle is preferably also provided with a bead 100. This end 98 is closed by a plug 102 made of a perforable material, or possibly pre-perforated. The cap 102 is forcibly engaged in the bottle beyond the bead 100. The cap 102 has in its upper face a recess 104, for example cylindrical. The side wall of the recess 104 is provided with a thread 106 whose function will be explained later. Preferably, the external lateral face 107 of the stopper has three sealing lips with the internal face of the body of the bottle.

 The guide part 14, which bears in this figure the reference 14 ′, is also modified by upper comparison is secured to a guide tube 122 and the lower end of which bears on the bottom of the plug 102.

The mode of use of the syringe device according to FIG. 6 is as follows:
The 10 'bottle is subjected to the operations already described to freeze-dry the product it contains. Then the guide piece 14 'with its syringe 12 filled with the liquid is fixed on the bottle 10' by screwing the skirt 112 of the guide piece on the external face of the stopper 102 of the bottle. The shoulder 110 of the guide piece comes to bear on the bead 100 of the bottle while the screwing tends to apply the upper free edge 124 of the stopper on the internal face of this same bead. The guide piece is thus secured to the bottle 10 'and the cap 102 is also immobilized in translation.

 Then the syringe 12 is pushed into the guide piece 14 '. The tip of the needle 34 perforated the part 120 and the stopper 102 thus ensuring communication between the interior of the vial 10 'with the interior of the syringe 12. Preferably, the tip of the needle 34 is substantially flush the internal face of the plug 120 as already explained. By moving the plunger 52 of the syringe, the liquid which it contained is passed inside the bottle 10 'and the liquid and the lyophilized product are mixed.

 We can then proceed to unscrew the guide piece 14 'relative to the cap 102 of the bottle 10' which becomes autonomous. The mixture is thus contained in a bottle which has one end provided with a perforable membrane 94 and the other end of which is closed by a stopper 102 which can serve as a piston. To do this, simply screw a control rod onto the thread of the plug 102.

 To administer to a patient the mixture contained in the bottle 10 ′, it suffices to mount a double-pointed needle on the perforable membrane 94 and to gradually insert the stopper 102 into the bottle, the stopper playing the role of piston.

 Likewise, the bottle 10 ′ can act as a liquid reservoir for a pump mounted on a tube connected to the bottle via its perforable membrane. In this case, the cap 102 will sink into the bottle under the effect of the suction of the liquid by the pump.

 In this latter embodiment, it is understood that the function of the threads 106 and 114 is, on the one hand, to temporarily secure the stopper 102 on the body of the bottle 10 'near its opening 18 in order to immobilize the plug 102 and thus allow perforation by the tip of the needle of the syringe and, on the other hand, to release in translation the plug 102, after removal of the guide piece 14 'so that the latter can play the role of a piston.

It goes without saying that one would not depart from the present invention if the syringe device were provided with other means capable of fulfilling this double function. For example, the stopper 102 could be provided with an external ring bearing on the periphery of the opening of the bottle 10 ′, thus preventing the plug from being pushed into the bottle. After removal of the guide piece 14 ', this ring would be broken to allow the plug 102 to be pushed in, which could then play its role as a piston.

 It is also understood that the embodiment of the bottle described in conjunction with FIG. 6 can be combined with the embodiment of FIGS. 3 and 4, that is to say in the case where the needle proper is replaced by the part. tubular 60 having the puncturing tips 62 and 64.

 Referring now to Figures 7a and 7b, we will describe an alternative embodiment of the guide piece which is then referenced 14 ". Inside the piece 14" is provided a guide piece 130, forming an integral part of the part 14 "comprising a collar 132 for connection to the part 14", a cylindrical portion 134 intended to receive the end of the body of the syringe when the latter is fully inserted in the part 14 "and a portion 136 for guiding the needle which is connected to the cylindrical portion 134 by a substantially conical portion 138. Radial fins 140, better visible in FIG. 7b, ensuring the centering of the guide part 130. The fins 140 have, at their lower ends, cutouts 142 defining a free volume 144 intended to receive the perforable part 80 in which the tip of the needle is pressed in. The perforable part 80 is integral with the guide part 130. Finally, above the flange 138, the zone 146 of the guide piece 14 "is intended to receive the seal 48.

 When the guide piece 14 "is mounted on the bottle, the perforable piece 80 is pinched between the stopper 22 of the bottle and the lower end of the guide portion 136. The perforable piece therefore seals the lower end of the guide portion 130 and it protects from contamination the perforable central portion of the plug 22. In addition, when the syringe is placed in the guide piece 14 ", the seal 48 seals at the other end of the guide part 130. During storage of the syringe device, the syringe needle is therefore entirely protected inside the guide part 130. This protection remains during all the operations of mixing the two products.

 Preferably, the syringe is placed in the guide piece and then this assembly is fixed to the bottle. In the case of the embodiment of FIGS. 7a and 7b, the interior of the part 130 is sealed off as soon as the body of the syringe cooperates with the seal 48.

The air contained in this closed volume can counteract the penetration of the syringe until it arrives in its storage position in which the tip of the needle enters the part 80. To allow the escape of the air during this phase, provision may be made for the temporary placement of a second needle which passes right through part 80 and opens out inside part 130. This second needle can subsequently be used for introduction into part 130 of a gaseous disinfection agent. Then the second needle is removed before fixing the part 14 "on the bottle. The perforable part being a septum, the orifice created by the introduction of the needle closes as soon as it is withdrawn.

 Referring now to Figures 8a to 8c, we will describe a new embodiment of the syringe device. According to this embodiment, the vial 10 and the syringe 12 may be identical to the corresponding elements shown in Figures 1 and 2 or 5. They will therefore not be described again.

 The guide piece 14 "'has a cylindrical body 150, one end 152 of which forms a snap-on fixing tip on the neck 20 of the bottle and the periphery of the stopper 22. At its second end the cylindrical body is provided with a protective flange 154 and it is extended by a housing 156 intended to receive a seal 158, preferably with a lip, which may be identical to that of FIG. 1. As already explained, this seal 158 provides the seal between the body of the syringe 12 and the guide piece 14 "'during all the relative movements of the syringe relative to the guide piece.

 Inside the cylindrical body 150 is a guide structure 160 which comprises a frustoconical portion 162 secured to the body 150 extended by a cylindrical end portion 164. In the end portion 164 is mounted a pierceable piece 166 made of an elastic material. Inside the cylindrical portion 164 is provided a sleeve 168 integral with the portion 166. The free end of the sleeve presses on the face 166a of the perforable piece 166. In addition, the second face 166b of the piece 166 is slightly projecting from the free end of the cylindrical portion 164. Thus when the guide piece 14 "'is fixed on the bottle 10, the perforable piece 166 is slightly compressed, which ensures pressure contact between the face 166b of the part 166 and the central part of the plug 22 intended to be perforated This arrangement can also be provided for the perforable part 80 or 120 of the embodiments of FIGS.

 FIG. 8a shows that the cylindrical body of the guide piece has an orifice 170 disposed above the zone of connection of the guide structure 160 with the cylindrical body 150. The orifice 170 is closed by a micro porous filter 172 , of a type known per se. The hydrophobic filter 172 has very small pores capable of maintaining the sterility of the volume limited by the guide structure 160. For example, the pores of the filter have dimensions of the order of 0.22 microns.

 Filter 172 has a dual function. On the one hand, it allows air to escape when the syringe 12 is pressed into the guide piece. This arrangement is extremely desirable because of the presence of the seal 158. On the other hand, it allows, after the positioning of the syringe in the guide piece 14 "'and the fixing of the latter on the bottle to introduce a sanitizing gas into the guide structure. It goes without saying that a micro-porous filter similar to the filter 172 in FIGS. 8 could be mounted on the guide pieces 14 in FIGS. 1 to 5, or 14 ′ and 14 "of Figures 6 and 7.

 FIG. 8a also shows that, preferably, the needle 34 of the syringe is equipped with a needle guard 180. The needle guard 180 comprises a cylindrical sheath 182 which surrounds the needle 34. Its first end 184 is perforating and made slightly protruding beyond the tip of the needle. The other end of the sheath 182 comprises a removable fixing part 186 on the injection end of the body of the syringe 12. When the syringe is placed in the guide part 14 "', the end 184 of the needle guard 182 is guided by the sleeve 168 of the guide structure.

In its final storage position, the point 184 of the needle guard partially perforates the part 166.

 Preferably, the fixing part 186 comprises a part made of elastic material 187 which seals between the end of the syringe carrying the needle and the needle guard 180.

 To mix the products, as already explained, the syringe is pushed into the guide piece (fig. 8b).

During this movement, it is the point 184 of the needle guard 182 which perforates the part 166 and the stopper 22 of the bottle 10; thus protecting the tip of the needle 34. Thanks to the material of which it is made, the needle guard 182 remains wedged by friction in the plug 22 and the part 166 (FIG. 8c) when the syringe 12 is removed from the part of guide 14 "'. The maintenance of the needle guard 182 can also result from friction between the fixing part 186 of the needle guard and the guide part 14"' or of a particular shape given to the latter which ensures its clipping on the guide piece.

 In the embodiments described above, the fixing of the guide piece on the bottle is obtained by a particular shape of the end 28 of the guide piece. Figures 9a to 9c illustrate another method of attachment.

 According to the embodiment of Figure 9a, the end of the guide piece 14 "'is constituted by a circular flange 220 intended to come to bear on the periphery of the stopper 22 of the bottle.

A crimping cap 222 in the form of a ring has a first curved part 224 which is engaged in a slot 226 of the flange 220 and a second cylindrical part 228. The free edge 230 of the cylindrical part 228 is intended to be crimped on the face lower neck 20 of the bottle to secure the guide piece 14 "'on the bottle.

 FIG. 9b illustrates a variant mounting of the crimping capsule 222. This has a folded portion 224 'which rests on the flange 220' forming the first end of the guide piece 14 "'. The rest of the crimping cap 222' is identical to that of the cap 222.

 FIG. 9c shows the fixing of the guide piece 14 "'of FIG. 9b on the bottle 10 provided with its stopper 22. The stopper 22 can already be fixed on the neck of the bottle by a first fixing capsule as shown in FIG. 1 or else this stopper can be simply pushed into the opening of the bottle. In both cases, the guide piece 14 "', in which the syringe has already been placed in a palace, is applied against the bottle of such so that the flange 220 'is in abutment against the periphery of the plug 22. We then proceed to crimp the free edge 230' of the crimping cap.

 It is understood that the solution illustrated in FIGS. 9a to 9c makes it possible to simplify the joining of the bottle 10 and of the part and of the guide part 14 "'since the crimping cap 222 or 222' already placed on the part of It goes without saying that this joining method can be applied to the embodiment described above by modifying the shape of the first end of the guide piece.

 Referring to Figures 10a to 10d, we will describe the use of a syringe device with an auto-injector. The syringe device is of the type shown in Figures 8a to 8c except that it does not include a needle guard. In addition, preferably, the clipping end 152 of the guide piece 14 "'is extended by a flange 190 forming a bearing surface as will be explained later.

 After mixing the two products and drawing the mixture into the syringe, as explained above, the guide piece 14 "'is separated from the vial 10 and the piston 52 is removed from the syringe 12 sa The syringe device is then in the state shown in Figure 10a.

 In the next step, shown in FIG. 10b, the syringe device is put into place in the cavity 200 of an auto-injector 202. The syringe 12 is arranged along the axis XX ′ of the cavity of the autoinjector and the syringe device is immobilized in translation, for example, by the cooperation of the flange 154 with recesses 204 and 206.

 FIG. 10c shows that the assembly thus prepared is placed on the patient to whom an injection of the mixture is to be made. More specifically, the zone 190 is placed in contact with the part 208 of the patient's body where the injection must be performed. By acting on the control button 210, the output of a first pusher 212 which projects into the cavity 200 and which bears on the open end 214 of the body of the syringe is controlled. The displacement of the plunger 212 causes the syringe to sink into the guide piece 14 "’ and therefore the needle 34 to sink into the patient's body by a predetermined length. During this operation, the piston 52 of the syringe is not moved relative to the syringe body.

 In the final operating phase shown in FIG. 10d, the actuation of a second pusher 216 coaxial with the pusher 212 is caused, the pusher 212 remaining stationary. the movement of the plunger 216 causes the plunger 52 of the syringe to sink in at a controlled speed until all of the mixture contained in the body of the syringe has been injected into the patient. Preferably, the actuation of the control button 210 causes the push-button 212 and the push-button 216 to be successively controlled.

 It is understood that, when the operator manipulates the syringe device in order to push the syringe into the guide tube to cause the perforation of the stopper of the vial, the external face of the syringe body which is external to the seal of the guide tube may be contaminated, particularly by the operator's hands. However, part of this surface, which is hatched in FIG. 8a, will penetrate into the sealed and sterile chamber defined by the guide tube and the seal. This risks causing contamination of this chamber and the parts of the device it contains.

 Figures 8a to 8c illustrate a first embodiment of these protection means. They consist of a cylindrical skirt 220 which extends beyond the external end of the seal 158.

The internal diameter of this skirt is greater than the external diameter of the body of the syringe. The axial length 1 of the skirt is at least equal to the stroke l 'of the syringe in the guide tube 14 "' between its storage position (fig. 8a) and its perforation position (fig. 8b). that thus the hatched area 222 of the external surface of the syringe, intended to penetrate into the tube, cannot be touched by the operator, which avoids the risks of contamination by contact with this area.

 Figures 1a to 1 tick illustrate a second embodiment of the annular protection means. These means consist of an elastic sleeve 224 which is mounted on the portion of the syringe body adjacent to the end of the seal 158 when the syringe is mounted in the guide tube. The hatched area is therefore protected against any risk of contamination by contact or by ambient air. The sleeve 224 has a length 1 which is at least equal to the stroke 1 'of the stroke of the syringe body in the guide tube. When the syringe is inserted into the tube, the seal constitutes a stop for the protective sleeve 22 ′, the latter sliding relative to the syringe body.

 It goes without saying that the annular protection means which have just been described in connection with Figures 8 and 1 1 could be used with the embodiments described with reference to Figures 1 to 7 and 9.

 FIG. 12 illustrates another embodiment of the syringe device which makes it possible to protect the assembly against the risks of contamination linked to the grasping of the syringe body by the user. The guide piece 14 "'has a running part 200 of frustoconical shape, an end 202 for fixing to the bottle 10 and a connection end for receiving a seal 206 and the syringe body 12. The fixing end comprises a flange 208 and members 210 for clipping onto the opening of the bottle. The clipping lugs can be completed by a crimping ring 212. Once in place, the ring 212 can penetrate a groove formed in the lugs clipping thus ensuring the locking of the guide piece on the bottle The collar 208 leaves a central zone 214 free for the passage of the needle 34. Preferably, the passage 34 is surrounded by a circular rib 216 which projects out of the collar 208. This rib cooperates with the stopper of the bottle 10 to ensure a seal between the two parts.

 The upper end 204 of the guide piece has an enlarged cylindrical shape in which the annular seal 206 is mounted.

This seal can be made of rubber (Butyl) or plastic. The seal 206 has a shoulder 218 which cooperates sealingly with an enlarged portion 220 of the syringe body. The seal 206 has on its outer face two sealing beads 206a and 206b which provide dynamic sealing while allowing the seal to slide under the effect of a thrust. On its lower edge, the seal preferably comprises an annular recess 222 which cooperates with a clipping rib 224 when the syringe is fully inserted in the guide part.

 It is understood that the interior of the guide piece containing the needle 34 is sealed, in particular with respect to germs of contamination due to the seal 206 and the sealing rib 216. In addition, the central zone of the the cap, which will be perforated by the needle, is also protected from the risk of contamination.

 The mode of use of the syringe device of FIG. 12 is as follows: in the storage position, shown in FIG. 12, the seal 206 is in the position not pressed into the guide piece.

When it is desired to mix the product contained in the bottle 10 with the liquid contained in the syringe, the syringe is pushed into the guide piece 14 "', which causes the simultaneous insertion of the seal 206 thanks to the cooperation of the shoulder 218 and of the part 220 of the syringe body. At the end of the insertion of the syringe, the clipping elements 222 and 224 cooperate and ensure the joining of the seal on the guide part. with the mixture, it suffices to extract the latter from the guide part, the joint remaining integral with the latter.

 It is important to observe that, thanks to the displacement of the seal 206 caused by the insertion of the syringe, the part of the syringe external to the guide piece in the storage position, which is liable to be contaminated by the user. , remains external to the sealed zone internal to the guide piece limited by the position of the seal 206. There is therefore, in the insertion phase, no risk of contamination of the needle.

 It may be advantageous to equip the current part of the guide piece with an orifice obstructed by a bacteriological filter, the assembly being represented by the reference 226. This filter authorizes the exit of air during the insertion of the syringe in the guide piece, while maintaining the asepsis of the space containing the needle 34.

 Several other alternative embodiments can be provided in the context of the invention. In particular, it is possible to provide that, when the syringe is withdrawn with respect to the guide piece, the needle separates from the end of the syringe by remaining planted, for example, in the perforable piece or in the cap.

 According to another alternative embodiment, the shape of the seal between the guide piece and the syringe body can be modified to facilitate separation of the syringe from the guide piece. For this, a thread is provided in the external face of the seal, this thread cooperating with a thread formed in the internal face of the guide piece. The internal face of the seal remains provided with its sealing lips. To separate the syringe from the guide piece, simply rotate the body of the syringe, which unscrews the seal. Of course, other removable attachment means could be used on the end of the guide piece.

Claims (17)

 1. Syringe device for mixing two compounds, at least the first of which is liquid, comprising a syringe (12) provided with an injection end (32), the syringe containing said first compound, characterized in that it further includes:  a bottle (10, 10 ') provided with an opening (18) and a stopper (22, 102) capable of sealingly closing the opening of said bottle, said stopper comprising a central perforable zone,  means (14, 14 ', 14 ") for guiding in translation the injection end of said syringe between a first recessed position called storage and a second depressed position called active, said guide means comprising a first end opening out opposite the perforable zone of said stopper and a second end (46) for receiving the injection end of said syringe, said second end comprising first sealing means between the body of said syringe and said guide means, and means for ensuring sufficient securing between said syringe and said guide means while allowing said translation; and  communication means (34, 60) to allow the perforation of said central zone and the communication of the internal volume of said syringe with the interior of said vial when the injection end of said syringe is brought into its second position.  2. Syringe device according to claim 1, characterized in that said first sealing means are capable of ensuring said sealing during the relative movement of said syringe (12) relative to the guide means (14, 14 ', 14 " , 14 "').  3 syringe device according to any one of claims 1 or 2, characterized in that said first sealing means comprise a seal (48, 158) mounted inside the guide means and cooperating with the external face of the body syringe.  4. Syringe device according to claim 3, characterized in that said seal has the shape of a ring whose face cooperating with the body of the syringe comprises at least two sealing lips.  5. Syringe device according to any one of claims 3 and 4, characterized in that said seal is made of elastomeric material.  6. Syringe device according to any one of claims 3 and 4, characterized in that said seal is made of plastic material.  7. Syringe device according to any one of claims 1 to 5, characterized in that it further comprises annular protection means surrounding a part of the body of said syringe to prevent manual access to the external face of said part of the syringe body, a first end of said protection means being adjacent to said first sealing means when said syringe occupies its first position in said guide means, the axial length 1 of the protection means between its first and second ends being at least equal to the stroke 1 'of said syringe in said guide means between its first and its second position.  8. Syringe device according to claim 7, characterized in that said annular protection means comprise a cylindrical skirt extending the external end of the first sealing means, said skirt having an internal diameter greater than the external diameter of the body of said syringe .  9. Syringe device according to claim 7, characterized in that said annular protection means comprise a sleeve mounted to slide on the body of said syringe, said sleeve having a first end which, when the syringe is in its first position, is adjacent at the outer end of said first sealing means.  10. Syringe device according to claim 3, characterized in that said seal comprises temporary means for securing in translation with the body of said syringe when said syringe is moved between its first and its second position.  11. Syringe device according to claim 10, characterized in that the temporary securing means comprise a shoulder formed in the face of the seal cooperating with a relief of the body of the syringe, whereby said seal is driven when the syringe body.  12. Syringe device according to any one of claims 10 and 11, characterized in that said cooperation means provide a seal between said seal and said syringe body.  13. Syringe device according to any one of claims 10 to 12, characterized in that said seal comprises a first locking element capable of cooperating with a second locking element when said seal is in its second position.  14. Syringe device according to any one of claims 10 to 13, characterized in that the face of said seal cooperating with the guide piece comprises at least two sealing lips.  15. Syringe device according to any one of claims 1 to 14, characterized in that said first end of the guide means comprises a flange capable of bearing on the opening of said bottle, and means of attachment to said bottle, said flange comprising in its face turned towards the bottle an annular projecting portion to cooperate in a sealed manner with the stopper of said bottle.  16. Syringe device according to claim 15, characterized in that said fixing means comprise clipping tabs cooperating with the periphery of the opening of the bottle.  17. Syringe device according to claim 16, characterized in that said clip means further comprises a crimping ring cooperating with the clip tabs.