Abstract:
A device for producing medicinal foam comprises a gas vessel for holding a sterile gas and an active agent vessel for holding an active agent. A connecting element connects both vessels. Further, a feeder for feeding the gas and the active agent back and forth between the two vessels is provided for producing the medicinal foam. The connecting element comprises a closure element for a sterile closure of one of the two vessels.

Description:
BACKGROUND OF THE INVENTION  
       [0001]     1. Field of the Invention  
         [0002]     The invention refers to a device for producing in particular reproducible medicinal foam or bubble suspension of a gaseous and a liquid medium. In particular, the invention refers to a mixing device for a reproducible preparation and administration of injectables such as sclerosing agents, diagnostic agents, therapeutic agents, homeopathic agents and autologous blood, for example.  
         [0003]     2. Related Prior Art  
         [0004]     Sclerotherapy means the planned elimination of intracutaneous, subcutaneous and/or transfascial varices and the sclerotization of subfascial vessels in case of venous anomalies by injecting a sclerosing agent. The various sclerosing agents cause damage to the endothelium of the vessels. Thereafter, a secondary vascular occlusion occurs and, in the long term, the veins are transformed into a strand of fibrous tissue, i.e. sclerosis occurs. It is the purpose of the sclerotization treatment to definitely transform the veins into a fibrous strand. This can not recanalize and, in its functional result, corresponds to the surgical procedure for removing a varice. Besides a sclerotization with liquid sclerosing agents, the sclerotization with foamed sclerosing agents becomes ever more important. The foam remains in vein for a longer period. Here, surfactant sclerosing agents, such as Polidocanol, are most often made to achieve a foamy state by pumping the agent back and forth between two pumps or by shaking, whereafter it is injected in a conventional manner. At present, there is no approved technique that would allow a reproducible preparation of a standardized foam.  
         [0005]     Further, a plurality of preparations suited for use as ultrasonic contrast media are known, some of which contain surfactants that support the formation of bubbles and stabilize these. The bubbles or a foam reflecting ultrasound are the true contrast medium and are produced only immediately before being administered.  
         [0006]     A mixing device for producing medicinal foam or for producing bubbles is known from EP 0 564 505. Here, a mixer with a helically shaped mixing element is described. The mixer is an accessory element that may be permanently connected to a syringe. When a liquid and/or gaseous medium is expelled from a second syringe, the medium reaches the mixer that contains the gas in a defined volume and nature. Here, the gaseous phase and the liquid phase are mixed along the helical mixing element. Thereby, a therapeutic and/or diagnostic foam may be produced. Due to the helical mixing elements arranged in the mixer, the mixer is a component that can only be produced as an injection molded part with intricate injection molds.  
         [0007]     Especially in producing foams for medicinal use, especially for sclerotherapy, it is necessary to produce a sterile foam. Should air be used to produce foam, it is possible to aspire air through a sterile filter into a syringe and to use the sterile air thus obtained to produce foam. However, this has the drawback of requiring an additional step and an additional component in the form of the sterile filter. This increases the costs. Further, the volume of waste is augmented.  
         [0008]     It is further known from GB 2 369 996 to close a syringe filled with sterile air using a three-way valve. A second valve is filled with an active agent and is also connected to the three-way valve so that the syringes are oriented under an angle of 90° to each other. Thereafter, the three-way valve is rotated to a position in which both syringes are in communication so that by pumping the gas and the active agent back and forth, foam can be produced. Closing a syringe filled with sterile air using a three-way valve has the drawback that, for example, during transport or handling, inadvertent opening and thus a contamination and/or a change in the gas volume can occur. Furthermore, the handling of this system is complex, since after both syringes have been connected to the three-way valve, the latter also has to be opened. Moreover, it is difficult to produce a reproducible foam with this device, since the diameter of the passage changes already at a slightly false position of the three-way valve. This can cause the production of a foam with a different size of bubbles. Further, the orientation of the two syringes under an angle of 90° is disadvantageous, since this makes the handling more difficult.  
         [0009]     Typically, after the production of foam both syringes contain foam. With the device described in GB 2 369 996, for therapy, one of the syringes filled with foam has to be unscrewed from the three-way valve. In order to additionally inject the foam remaining in the second syringe at a later time, if necessary, it is required to close the three-way-valve so as to avoid contamination. To then inject the remaining foam, the first syringe just used for therapy must be screwed to the three-way valve again and the valve has to be opened, to then transfer the remaining foam into the injection syringe, for example. Thus, this procedure is extremely complex.  
         [0010]     It is an object of the invention to provide a device for producing medicinal foam from a gaseous and a liquid medium, the device being adapted to meet high sterility demands.  
       SUMMARY OF THE INVENTION  
       [0011]     The present device for producing medicinal foam that is particularly suitable for use in scleroscopy, comprises a gas vessel for holding a sterile gas, especially sterile air. Further, an active agent vessel for holding a usually liquid active agent is provided. Preferably, both vessels are syringes, in particular disposable syringes. Both vessels are adapted for fluidic connection to a connecting element. Moreover, a feed means is provided for conveying the gas and the active agent back and forth between both vessels so as to produce the medicinal foam. In a preferred embodiment, the feed means comprises two feed elements, each feed element being connected with one of the two vessels, respectively. Preferably, the feed elements are the syringe pistons.  
         [0012]     According to the invention, the connecting element is connected with one of the vessels, preferably the gas vessel. The connection is obtained for example by screwing, especially by means of a Luer lock. Similarly, the connecting element may be permanently connected with the vessel, e.g. glued thereto or formed integrally therewith. Specifically, the hub with the opening of the syringe can be formed as a connecting element. Preferably, the connecting element is surrounded by the Luer lock. According to the invention, the connecting element comprises a closure element for the sterile closing of the vessel. Thus, it is possible to provide a sterile gas, e.g. sterile air, in one of the two vessels, especially in the gas vessel, which can not escape from the vessel because of the closure element provided. An undesired intrusion of non-sterile air is also avoided because of the closure element provided according to the invention. Thus, in a particularly preferred embodiment, the connecting element is configured such that in the unconnected state, i.e. especially before the gas vessel together with the connecting element is connected to the active agent vessel, both an intrusion and an escape of gas and/or liquid into or from the vessel closed by the closure element is prevented. This has the advantage of ensuring a very good sterility of the medium contained in the vessel. Further, it is ensured that an unintentional change of the gas volume is avoided. Thereby, a good reproducibility of the medical foam is ensured.  
         [0013]     Preferably, the closure element comprises a resilient rubber stopper. The stopper may comprise a slit serving to open the closure element. The slit is configured such that the slit walls abut each other in the unconnected state and close the vessel tightly, such that an intrusion or an escape of gas and/or liquid is avoided.  
         [0014]     Preferably, the closure element is opened automatically upon connecting the connecting element with the second vessel, in particular the second syringe. In a preferred embodiment, this guarantees that by opening in the manner provided by the invention contamination is avoided by the connection, other than when removing a closure element in the form of a lid or the like. Further, no additional step such as removing a lid or opening a valve is required. According to the invention, this specifically allows to provide a closure element with a significantly lower risk of contamination.  
         [0015]     The present device for producing medicinal foam has the particular advantage that the sterile gas is preferably already present in a sterile condition and does not have to be obtained first through a sterile filter. Further, due to the automatic opening, the gas remains sterile so that an inadvertent contamination by aspiration is avoided. Moreover, it is guaranteed that the exactly defined volume of gas, and thus the mixing ratio of gas and agent, will not be corrupted for example by an unintentional escape of gas. Thus, it is possible to produce a reproducible foam and to create a standard.  
         [0016]     Creating a high standard or a high uniformity of the foam producible with the present device can be improved further by also prefilling the second vessel. To this effect, the second vessel, which is especially the active agent vessel, is closed by a closure member. The closure member may be configured similar to the closure element, in particular as a membrane or a plastics stopper. When two prefilled vessels are provided, one of which is closed with the connecting element including the closure element, this is further advantageous in that a further process step, i.e. filling the still empty vessel, usually the active agent vessel, can be omitted.  
         [0017]     Preferably, the closure element is opened by penetrating a membrane of the closure element. The penetration of the membrane may be effected by a hub on the second vessel, especially provided at the syringe, in particular the hub of a Luer lock. In particular, the closure element is opened such that the process is reversible and the closure element therefore closes the vessel again, when in the unconnected state. Specifically, the membrane or the plastics stopper are configured such that it has a slit which may be spread open by means of a tubular element, for example, and closes again when the tubular element is withdrawn.  
         [0018]     In a particularly preferred embodiment, the connecting element comprises a tube element. When connecting the second vessel with the connecting element, the membrane is penetrated by the tube. For this purpose, the closure element and/or the tube element are preferably arranged for displacement in the connecting element. Here, the tube element is preferably held fixed in the connecting element so that a displacement of the closure element causes a penetration of the membrane by the tube element. The closure element is preferably displaced by a hub of the vessel, in particular the Luer lock hub of a syringe.  
         [0019]     As soon as the vessels are connected through the connecting element, the gas and the active agent can be pumped back and forth between the two vessels, in particular the two syringes, to produce the sterile foam. In doing so, the gas and the active agent preferably flow through the tube element. Specifically, there is no flowing around the closure element. This is advantageous in that clearly defined flow paths and thus a clearly predeterminable flow behaviour are given. This increases the reproducibility of the medicinal foam.  
         [0020]     To ensure a secure closing of the first vessel prior to the connection with the second vessel, the closure element is preferably spring-loaded. Upon opening the closure element, the closure element is preferably urged against the spring force. The spring force may be caused, for example, by a coil spring or another resilient element. The provision of such a closure element guarantees that the filling amount in the vessel remains constant and is not changed, e.g., during transport or handling. Further, the gas vessel can be closed again and has good sterility.  
         [0021]     Preferably, the connecting element comprises a mixing element. It is particularly preferred that the tube serving to open the membrane is designed as a mixing element. It is sufficient to provide a tubule with a small cross section so that turbulences are generated by the change in cross section, which turbulences serve to intermix the active agent with the gas. The tube element, preferably made of stainless steel or having a coating resistant against the active agent, has an inner diameter of up to  3  mm, for example. One of the openings of the tube may have its cross section reduced directly or indirectly by providing an additional element. The cross section is preferably reduced to a cross section of 0.3-2 mm. Tests have shown that a medicinal foam of very high quality can thereby be obtained with a very good reproducibility. In addition, barriers, deflecting elements and the like may for example be provided within the mixing element to ensure the generation of sufficient turbulences.  
         [0022]     The present device has the particular advantage that, due to the design of the connecting element, it is not necessary, for example after the production of a foam, to close a valve or the like, to avoid contamination of foam remaining in one of the syringes, for example. This is not necessary since an automatic closure is performed by the closure element when the syringe is removed from the connecting element. In particular for a later removal of the foam remaining in the syringe, a simple and safe reconnection of the syringe used for injection and the connecting element can be made. The handling of the present device is thus very simple while ensuring great safety.  
         [0023]     Further, the invention refers to a vessel, such as a syringe, particularly useful in the present device. The vessel, preferably filled with gas, is connected to a connecting element comprising a closure element. The connecting element, particularly adapted to be connected with a second vessel, especially a second syringe, is preferably embodied as described above.  
         [0024]     The invention further refers to a kit for producing medicinal foam comprising the above described first vessel, in particular filled with gas and closed with the connecting element. Moreover, the kit comprises a second vessel which, as the first vessel, is a syringe, in particular. In addition, the kit may comprise an active agent vessel, such as an active agent ampoule containing a sclerosing agent, for example. To produce the medicinal foam, the active agent is filled from the active agent vessel into the second vessel. Preferably, this is done by suction into the second vessel configured as a syringe. Possible, the kit my additionally comprise a needle for that purpose.  
         [0025]     In an alternative embodiment of the kit, the second vessel, in particular the second syringe, instead of the active agent vessel is already filled with an active agent and closed with a closure means as described above.  
         [0026]     In a particularly preferred embodiment of the kit the two vessels, which are conventional syringes in particular, are prefilled and connected with each other through the connecting element. However, the connection is such that the closure element of the connecting element is not yet open. This may be achieved, for example, by the fact that the second vessel, especially the second syringe, is not yet fully screwed to the connecting element using the Luer lock. The connection between the two vessels is then established by fully screwing or connecting the second vessel with the connecting element.  
         [0027]     Such a kit has the particular advantage that the medicinal foam can be produced very quickly. Not tome consuming preparatory steps are required. This may increase acceptance with practitioners. Further, the risk of contamination while connecting individual components is avoided. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0028]     A full and enabling disclosure of the present invention, including the best mode thereof, to one of ordinary skill in the art, is set forth more particularly in the remainder of the specification, including reference to the accompanying drawings in which  
         [0029]     In the figures:  
         [0030]      FIG. 1  is a schematic sectional side view of the connecting element,  
         [0031]      FIG. 2  is a schematic sectional side view of the connecting element connected with two vessels,  
         [0032]      FIG. 3  is a schematic sectional partial view of the connecting element together with the closure element of another embodiment,  
         [0033]      FIG. 4 a  schematic top plan view of the embodiment illustrated in  FIG. 3 , and  
         [0034]      FIGS. 5-7  schematic sectional partial views of the connecting element together with the closure element of other embodiments. 
     
    
     DESCRIPTION OF PREFERRED EMBODIMENTS  
       [0035]     A connecting element  10  comprises a cylindrical hub  12  with an inner thread  14 . A channel  18  is formed within the hub  12  by a tube element  16 , especially of circular cross section. A tube  20  is arranged in the channel  18 , extending over almost the entire length of the connecting element. At one end face  22 , the tube element  16  has an opening  24  opening into the channel  18 .  
         [0036]     A housing element  26  is connected with the hub  12 . The connection may be obtained along a contact surface  28  by glueing. Similarly, the two parts may be screwed together or connected otherwise. A circular cylindrical cavity  35  is formed in the housing  26 . A coil spring  32  is arranged in the cavity  30 , which urges a closure element  34 , also provided in the cavity  30 , outward against a stop  36  which, in the embodiment illustrated, is a chamfer. The closure element  34 , which comprises a membrane  42  and a sleeve in the embodiment illustrated, is a resiliently deformable element which can be pushed into the housing element of  FIG. 1  from the right in a compressed condition, restores to its original shape within the housing  26  and is then held in the housing  26  because of the stop  36 . Similarly, it is possible to design the housing  26  as two parts to facilitate the mounting of the closure element  34 . in this instance, the housing  26  can be separated such that the closure element  34  is possible from the left in  FIG. 7 .  
         [0037]     The closure element, as well as the housing  26  and the hub  12 , is rotational symmetric to a center line  38  of the closure element  10 . The front side  10  of the closure element  34  is closed by a membrane  42 . The membrane  42  has a slit  44 . The slit  44  is illustrated in the drawing for the sakes of clarification. Actually, the membrane portions abut each other in the state illustrated in  FIG. 1  so that the slit  44  is closed, yet may be opened easily ( FIG. 2 ).  
         [0038]     The connecting element  10  may be connected with a gas vessel  46  and an active agent vessel  48 , the two vessels  46 ,  48  preferably being conventional syringes with Luer lock connections  50  or  52 , respectively. For transport and prior to mixing the gas in the gas vessel  46  with the active agent present in the active agent vessel  48 , only the gas vessel  46  is connected to the connecting element. To do this, the Luer lock connector  50  of the gas vessel  46  is screwed into the hub  12 . Because of the opening  24 , a fluidic connection exists between the inner space  54  of the gas vessel  46  and the channel  18  in which the tube  20  is arranged.  
         [0039]     Prior to inserting or screwing the liquid vessel  48  or the Luer lock  52 , respectively, the vessel  46  is closed tightly due to the closure element  34 .  
         [0040]     By screwing or inserting the Luer lock  52  into the housing  26 , the closure element  34  is pushed into the connecting element  10  in the direction of the arrow  56 . Here, the slit  44  of the membrane  42  is opened or the membrane  42  is penetrated. Because of the opening  58  provided in the tube, the inner space  60  of the active agent vessel  48  is also fluidically connected with the channel  18 .  
         [0041]     By actuating the syringe pistons or a feed means, the active agent may be pumped from the inner space  60  through the tube  20  or the channel  18  into the inner space  54 , and the gas may be pumped from the inner space  54  through the tube  20  into the inner space  60 . This causes an intermixing of the gas and the active agent and then the gas and the active agent are pumped back and forth together between the two spaces  54 ,  60 . Thus, the medicinal foam is produced. This has the advantage that the force exerted for example on the syringe piston, as well as the pump rate can be adjusted or are defined. Thereby, the standardization of the foam produced is further enhanced.  
         [0042]     The tube  20  serves as the mixing element and may possibly comprise additional deflecting or mixing elements inside. Further, deflecting or mixing elements can also or additionally be arranged at the inlet and/or the outlet of the tube  20 . Possibly, in addition to or instead of the above described mixing elements, mixing elements may also be provided in other regions of the devices through which the active agent and the gas flow. Moreover, the length off the pipe  20  is selected feasibly, in particular empirically. According to the invention, the change in cross section caused by the opening  24  and the opening  58  is sufficient for intermixing.  
         [0043]     FIGS.  3  to  7  illustrate further embodiments of the present connecting element with different closure elements. In  FIGS. 3-7 , identical or similar components are given the same reference numerals.  
         [0044]     In the embodiment shown in  FIGS. 3 and 4 , a plastics or rubber stopper  62  is provided as a closure element in the housing  26 . The plastics stopper  62  may be mounted as described above with reference to the closure element  34 . the plastics stopper  62  has a slit  64  which is spread apart when the plastics stopper  62  is moved in the direction of the arrow  66 . When the plastics stopper  62  is pushed back into the position shown in  FIG. 3  by the spring  32 , the slit  64  is closed again automatically.  
         [0045]     In the embodiment illustrated in  FIG. 5 , the plastics stopper  62  additionally comprises a recess  68  directed towards the tube  20 , so that the tube  20  is positively guided and a secure opening of the slit is guaranteed.  
         [0046]     In the embodiments shown in  FIGS. 6 and 7 , the plastics stopper  62  is not opened with the aid of the tube  20 , but with a needle  70  or  72 , respectively. In this case, the needle  70  is either open in the direction of the stopper or the needle  72  has a lateral opening  74 . By providing the lateral opening  74  turbulences are created which, depending on the active agent used, allow for an enhanced production of foam. When needles  70 ,  72  are provided, the slits  64  may be omitted.  
         [0047]     Although the invention has been described and explained with reference to specific illustrative embodiments thereof, it is not intended that the invention be limited to those illustrative embodiments. Those skilled in the art will recognize that variations and modifications can be made without departing from the true scope of the invention as defined by the claims that follow. It is therefore intended to include within the invention all such variations and modifications as fall within the scope of the appended claims and equivalents thereof.