FR2705898A1 - Syringe device for mixing two compounds - Google Patents

Abstract

The invention relates to a syringe device for mixing two compounds. The syringe device comprises: a bottle (10) provided with an opening (18) and with a plug (22) comprising a central perforable region, means (14) for guiding the injection end of the said syringe in translation between a first so-called storage position which is set back and a second inserted position, the said guide means comprising a second end (46) for receiving the injection end of the said syringe; and connection means (34) for making it possible to perforate the said central region and connect the internal volume of the said syringe to the inside of the said bottle.

Description

SYRINGE DEVICE FOR MIXING
TWO COMPOUNDS
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 the lyophilization installations preferably accept containers of standard shape made of glass and with a flat external 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 medicines are already available in this form and any modification of packaging would require a new marketing authorization.

 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.

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 open end opening out opposite the perforable area of said stopper and a second end for receiving the injection end of said syringe; 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 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.

 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.

 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 which 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 the mixture of the two compounds, the perforable partition preferably being 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.

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 the figure 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; and
- Figure 6 is a partial view in longitudinal section of a fourth embodiment of the syringe device comprising a vial of modified type.

 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 whose end 38 cooperates sealingly with the injection end 32 of the syringe and whose second end 40 is puncturable 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 vial 10. As will be explained later, other methods of protecting the needle can be used. Preferably, 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 a displacement in translation of the syringe inside the guide piece 14 while maintaining the seal throughout the translation. 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 FIG. 1 also shows, preferably, a second shoulder 50 is provided inside the guide piece 14 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 so limit as much as possible the dead volume in the bottle when it is desired to recover by suction, 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 piston control rod 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.

 Preferably also, the guide piece 14 is made of a synthetic material 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 cartridge 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.

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 applies to 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 disposed 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.

 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 to the bottle a cutout which allows tearing of the latter, 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 it by means of radiating fins such as 84. In this figure, the internal additional shoulder 85 has also been shown already described in connection with the first two modes an embodiment which makes it possible to limit the insertion of the syringe into 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 part of g uidage.

 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, or possibly pre-perforated, the periphery of which has a groove which cooperates with a bead 96 on the bottom. 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 piece 14, which in this figure has the reference 14 ', is also modified with respect to the guide pieces shown in Figures 1 to 5. The end 108 for connecting the guide piece has an external shoulder 110 and it is extended by a skirt 112 of reduced diameter compared to that of the current part of the guide piece. This skirt 112 is provided on its outer face with a thread 114 which can cooperate with the thread 106 of the plug. Finally, as in the case of FIG. 5, the end of the needle is planted in a perforable piece 120 whose upper end is secured to a guide tube 122 and whose lower end is supported on the bottom of 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.

Claims (25)

 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 ') 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 open end opening into sight of the perforable area of said stopper and a second end (46) for receiving the injection end of said syringe; 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 bottle (10) is provided with a bottom.  3. Syringe device according to claim 2, characterized in that said first end of the guide means comprises means (28) for securing on the opening (18) of said vial (10).  4. Syringe device according to claim 3, characterized in that the means for securing (28) the guide piece (14) on said vial further comprises means for sealingly securing the periphery of said cap (22) on said bottle (10).  5. Syringe device according to any one of claims 1 to 4, characterized in that said securing means (28) can be broken to allow the separation of the vial (10) relative to the guide piece (14).  6. Syringe device according to any one of claims 1 to 5, characterized in that the communication means comprise a needle (34) mounted at the injection end of the syringe and the tip of which is adapted to perforate the central zone of the stopper (22) when the end of the syringe is brought into its second position.  7. Syringe device according to any one of claims 1 to 6, characterized in that the means of communication include a tubular part (60), a first end (64) of which is capable of closing off the central zone of the stopper ( 22) and the other end (62) of which is capable of piercing a perforable partition (70) formed at the injection end (32) of the syringe (12) when the latter is brought into its second position.  8. Syringe device according to claim 7, characterized in that said tubular part is constituted by two needles between which is disposed a filter.  9. Syringe device according to claim 6, characterized in that it further comprises a cap (36) surrounding said needle (34) and one end of which is pierceable by the point of said needle when the end of said syringe is brought into its second position.  10. Syringe device according to claim 9, characterized in that said cap (36) is made of a deformable elastic material and in that it extends over the entire length of the needle when the injection end (32) of the syringe is in its first position.  11. Syringe device according to claim 6, characterized in that it further comprises a perforable part (80) integral with the guide means (14) and in which the end of the needle (34) is depressed.  12. A syringe device according to any one of claims 9 to 10, characterized in that said cap (36) comprises immobilization means (42) in translation inside said guide means (14).  13. Syringe device according to any one of claims 1 to 8, characterized in that it further comprises an axial guide tube (82) integral with said guide means (14) and surrounding the needle when the syringe is placement in the guide means.  14. Syringe device according to any one of claims 1 to 13, characterized in that it further comprises a rod for controlling a piston of the syringe, said rod being screwable into said piston (52).  15. Syringe device according to any one of claims 1 to 14, characterized in that said stopper (22) has on its periphery (24) passages (26) which communicate with the outside with the inside of the bottle when the plug is in the partially depressed position and which are closed when the plug is fully depressed.  16. Syringe device according to any one of claims 1 to 15, characterized in that said guide means (14) are provided near their second end (46) with sealing means (48) for sealing between the guide means and the body (30) of said syringe.  17. Syringe device according to any one of claims 1 to 16, characterized in that said guide means (14) have a first internal shoulder (49) to limit the insertion of the body of the syringe into said guide means , so that the end of the needle does not pierce the plug (22) in the storage situation.  18. Syringe device according to any one of claims 1 to 17, characterized in that said guide means comprise means (50) for limiting the penetration of the body of the syringe when it arrives in its second position, such that the end of the communication means (34, 60) in this position is substantially in the plane of the internal face of said plug (22).  19. Syringe device according to claim 5, characterized in that after rupture of said securing means (28) and removal of the vial (10), said first end of guide means forms a support zone for injection and in that said guide means comprise an internal shoulder (85) to limit the insertion of the syringe into said guide means (14) beyond said support zone so that the end of the needle protrudes out of said support zone.  20 Syringe device according to claim 1, characterized in that said vial (10 ') comprises at its end opposite to said opening (18) a perforable membrane (94).  21. A syringe device according to claim 20, characterized in that said stopper (102) is slidably mounted sealingly inside said bottle (10 ').  22. Syringe device according to claim 21, characterized in that said stopper (102) comprises means of temporary securing to said vial (10 ') near its opening (18).  23. Syringe device according to claim 22, characterized in that said temporary fastening means comprise a first thread (106) formed in said plug (102) able to cooperate with a second thread (114) formed at the end (108 ) connecting said guide piece (14 ').  24. Syringe device according to any one of claims 1 to 23, characterized in that said stopper (22, 102) is pre-perforated.  25. syringe device according to any one of claims 1 to 24, characterized in that the guide means (14, 14 ') externally comprise a projecting portion (51) capable of protecting the fingers relative to the needle when holding the guide means.