Abstract:
A system and a method for making an injectable mixture using at least one first pulverulent component and a second liquid component with a first piston/cylinder arrangement with a cylinder with an axial extension and a piston, wherein the cylinder includes a measured amount of the pulverulent component, a separate reservoir including a corresponding measured amount of the liquid component, and a transfer device for sealed transfer of said amount of the liquid component to the cylinder for subsequent mixing and injection of the completed mixture. The first piston/cylinder arrangement is an injection syringe. A mixing element being manoeuvrable by a user is positioned inside the cylinder. At least one gas transferring channel means leading to the cylinder is arranged at the cylinder. Engagement means are arranged for connecting the first injection syringe to the separate reservoir during transfer of the liquid component.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation application of International Application PCT/SE2008/000552, filed on Oct. 10, 2008, which claims priority to SE 0702267-6, filed on Oct. 10, 2007, the disclosures of which are incorporated herein by reference in their entirety. 
     FIELD OF THE INVENTION 
     Systems and methods for making an injectable mixture for medical purposes using at least one pulverulent component and one liquid component are provided. 
     BACKGROUND OF THE INVENTION 
     It is previously known to introduce different paste-like materials into the human body for medical and in particular orthopaedic purposes. Such materials are often called bone cement, bone replacement material or “bone grafts” (hereinafter referred to as “bone cement”). These material can be of different types, for example based on synthetic or ceramic material and be used for filling voids in bone tissue or for supporting fastening of implants on bone tissue. 
     A known bone cement is based on settable synthetic material, in particular an acrylic plastic—polymethylmetacrylate (PMMA), which is commonly used in different orthopaedic applications. Traditionally bone cement is used in hip joints and in knee joints but lately also for filling voids in vertebrae, in wrists and more applications. The bone cement may be a two-component material wherein the starting materials are comprised of one pulverulent component and one liquid component, which have to be thoroughly mixed in accurately measured amounts for obtaining a good result. 
     It is known that the hardening is relatively fast and during heat release, which later escalates the hardening process, which is the reason that it is important that the process of mixing and application of the bone cement is relatively fast in order not to jeopardize quality of the result. 
     At present mixing is often undertaken by providing measured amounts of the two components into a mixing bowl wherein mixing is obtained through manual agitation. 
     Thereupon the mixture is transferred over a funnel and a supply pipe to an injection device including a piston cylinder unit. 
     In respect of this technology, strict requirements for sterility of the bone cement can be difficult to withhold during such preparation. Toxic vapours resulting from the components also are a risk factor for a person handling the material. 
     In another common arrangement, pulverulent and liquid components are provided separately to a mixing device wherein a mechanical mixer provides the agitation. 
     Background art includes U.S. Pat. No. 5,435,645 and WO 2005/053581. 
     SUMMARY OF THE INVENTION 
     It is an aim of the present invention to provide a system and a method as above which address above problems in the direction of at least mitigating them. 
     This is achieved in respect of the system according to above through the features disclosed herein. 
     Hereby is achieved that a system is created which is simple to handle for a user, and which is suitable for larger as well as very small mixture amounts, for example very small amounts of bone cement, as example about 1-20 ml, for precision application in narrow cavities in connection with open surgery as well as minimally-invasive surgery. 
     The system is, however, also suitable for use in respect of greater amounts of bone cement as well as other types of mixtures for medical purposes. By providing a mixing element ensures the possibility of adequate and thorough mixing and thereby high quality of the mixture. By providing a gas transferring channel means, a possibility is obtained on the one hand for de-aerating the completed mixture, and on the other hand to supply a sterilizing gas to the pulverulent component. 
     The first injection syringe and the separate reservoir can be connected or “docked” in connection with the transfer of the liquid component. Hereby is guaranteed that the closed transfer is safe and according to high hygienic requirements at the same time as the different components, the first injection syringe and the second piston/cylinder arrangement, can be handled separately and be treated in such ways that are suitable for the different components. 
     Hereby can be mentioned that the two components of some bone cements, such as for example today&#39;s PMMA-based cement, can not be sterilized with the same method, because one method which is suitable for one component can be ineffective or harmful for the other component. For that reason it is important that a system that can be used for a plurality of different cements on the market has separate containers for the different component so that the system gives the possibility of applying different sterilizing methods when used for bone cements where it is necessary. 
     Concerning bone cements of the mentioned kind, the liquid component has generally one commercially and technically applied sterilizing method which is aseptic filling over a sterile filter. The pulverulent component can be gas sterilized (ETO) or be sterilized through radiation. During gas sterilization, a pulverulent component which is pre-filled and inside a package for a packed syringe inside a package of a material which is permeable to the sterilizing gas but micro biologically tight is subjected to an atmosphere with this sterilizing gas. The gas can thus penetrate a package material, reach the syringe and subsequently reach and sterilize the pulverulent component through the gas transferring channel means. In practice, the packaged syringe is put inside a kind of a gas vessel, wherein for example is created an under-pressure, whereupon supplied sterilizing gas is sucked into the syringe and thereby the pulverulent component over said gas transferring channel means. After completed gas treatment, the gas is sucked out from the package over the same channel means and through the package material. 
     By the gas transferring channel means being displaceably arranged inside the cylinder and in particular a mouth of the gas transferring channel means being displaceable in the axial direction of the cylinder, very effective de-aerating of the mixture after completed mixing is possible. During mixing, air enclosures are created inside the mixture, which could seriously deteriorate the quality of the mixture/bone cement or the like. Bone cement is namely often relatively highly viscous and air enclosures can therefore not simply be shaken or pressed out in an effective manner. Through this aspect of the invention, however, a gas transferring channel means can be brought to “search” for these air enclosures through its displacement inside the cylinder, normally during simultaneous activation of the first injection syringe, such that a minor over-pressure prevails therein. Considerably more effective de-aeration of the complete mixture body can therefore be achieved through the invention. 
     The invention is particularly suited for preparing paste-like mixtures, wherein it&#39;s usual that the air enclosures remain in the completed paste. The invention has, however, also its application for other mixtures wherein air bubbles easily become more permanently remaining after completed mixing procedure. It can be in respect of somewhat jelly-like or syrupy mixtures. 
     By the separate reservoir being included in a second piston/cylinder arrangement and in particular in a second injection syringe, standard components can be used, which are easy to handle and economically advantageous. Through this arrangement it is possible to introduce a very precise amount of the liquid component into the cylinder such that high quality can be reached for the mixture. 
     By the second engagement means being releasable, the first injection syringe can be freed from the second piston cylinder arrangement after completed transfer of liquid component for further handling of the completed mixture. It is rational and preferred that a means for manoeuvring the mixing element also includes said gas transferring means. Hereby it is achieved in a simple manner that these functions are integrated and hereby the possibility of de-aerating according to the above is simplified. 
     It is preferred also that said gas transferring channel means is comprised of a transfer channel means for transferring the liquid component from the second piston/cylinder arrangement, whereby further integration of different functions into the system is achieved. 
     It is also preferred that a means for manoeuvring the mixing element includes said transfer channel means. 
     In the cases where the first, and on occasion the second, injection syringe are single use articles the problems with cleaning and reusing of these details are avoided and in case they are comprised of standard components, an economically advantageous solution is obtained. 
     It is thus preferred that the system is adapted for use in connection with the application of bone cement into a patient, but also use within other medical applications are envisaged such as for medical mixtures with the property that they bind air enclosures and therefore should be de-aerated before being administered. 
     The corresponding advantages are obtained in respect of a method according to the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention shall now be described in more detail by way of embodiments and with reference to the annexed drawings. 
         FIGS. 1   a - c  show different steps for filling and sterilizing a pulverulent component into a first injection syringe. 
         FIG. 1   d  shows a free holder means in the form a needle shaped element. 
         FIGS. 2   a  and  2   b  show two steps in connection with filling a liquid component into a second injection syringe. 
         FIGS. 3   a - f  show different steps in connection with mixing components before application of the mixture. 
         FIGS. 4   a - c  show a modified first injection syringe in different views. 
         FIGS. 5   a  and  5   b  show filling of a modified second injection syringe. 
         FIG. 5   c  shows an adapter for filling. 
         FIG. 6  shows the modified first injection syringe docked to the modified second injection syringe. 
         FIG. 7  shows an injection needle for use with a system according to the invention. 
         FIG. 8  shows the modified first injection syringe in connection with associated components. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     Like and similar elements in the different embodiments have been given the same reference numerals. 
     With reference to  FIGS. 1   a - 1   c  the process of sterilizing a pulverulent component  2  inside the first injection syringe  1  is shown. In  FIG. 1   a  is diagrammatically shown a first filling station, whereby a dosing and filling device  3  is arranged to deliver a measured amount of the pulverulent component  2 , which falls down into a cylinder  2  of the first injection syringe  1 . 
     First injection syringe  1  is also provided with a mixing element  4  which is connected to a manoeuvring means  7 - 8  for making it possible to rotate the mixing element  4  and to make it possible to displace it in an axial direction of the cylinder during a later mixing operation. 
     A tubular portion  7  of the manoeuvring means  7 - 8  having an inside channel extends from the mixing element  4  through a passage (not shown) in a connection portion  5 , to a first engagement means in the form of an outside thread on a rotation portion  8 . The connection portion  5  has an outer male thread (not shown) for later application of a chosen injection needle when the completed mixture is to be injected. 
     From  FIG. 1   d  shows a free holding means  28  in the form of a needle-shaped element  30 , which is rigidly connected to a fastening element in the form of a sleeve-shaped element  29 , which has means such as inside female threads  29 ′ for co-operation with corresponding fastening means such as the above-mentioned male threads on the connection portion  5 . Also other fastening principals can be envisaged such as bayonet connection means. 
     The aim of the free holding means  28  is that after filling with pulverulent component  2  and until the point where mixing of the two components is to be made, prevent the pulverulent component  2  from penetrating into the channel inside the tubular portion  7 , which otherwise could risk blocking the latter for gas transfer and later transferring of a liquid component. In the embodiment shown in  FIG. 1   d , the needle-shaped element  30  of the free holding means  28  is hollow all over its length and together with the sleeve shaped element  29 , which has a recess  31 , there is formed a gas penetrable connection through the free holding means  28  such that gas can penetrate from the outside to the inside of the first injection syringe  1  for sterilizing purposes. Certain gas transfer can also be had between the envelop surface of the needle-shaped element  30  and the channel wall of the tubular portion  7 . 
     In  FIG. 1   b  is shown in a second stage that a piston  20  with a piston rod  21  for its manoeuvring is introduced into the free end of the cylinder of the first injection syringe  1 , which is filled with pulverulent component  2  for forming a first piston/cylinder arrangement. 
     In  FIG. 1   c  is shown in a third stage the first injection syringe  1 , filled with pulverulent component  2 , is placed in a chamber  9 , which is arranged from a gas container  10  over a gas conduit  11  to feed a sterilizing gas into the chamber  9  enclosing a package with the first injection syringe  1 . With reference to the above, sterilizing gas can thus penetrate into the inside of the first injection syringe  1  over, to start with, the recess  31 . After completed sterilization, the first injection syringe  1  is ready for delivery/use. It should be noted that other solutions for achieving gas transfer is within the scope of the invention such as for example that all gas transfer is between an envelope surface of a non-hollow needle-shaped element  30  and the channel wall of the tubular portion  7 . 
     Also other per se known sterilizing methods for different uses of the invention are within the scope of the invention. It is thus possible to use radiation sterilization with ionizing radiation or for example certain electromagnetic radiation with sufficient power for the purpose. It is also possible to use heating in dry heat or dry heat atmosphere in certain instances. 
     In  FIG. 2   a  is shown a first stage for filling a liquid component  13  into a second injection syringe  12 . Hereby is in a corresponding manner as during filling of the first injection syringe  1 , the second injection syringe  12  arranged for receiving a measured amount of the liquid component  13  contained inside a supply  16  over a feed pump  15 , which is arranged to provide the inside of the second injection syringe  12  with said measured amount of the liquid component over a liquid conduit  17  and a sterile filter  14 . 
     On the lower part of the second injection syringe, as shown in  FIG. 2   a , is arranged a closure  19  with second engagement means  18  in the form of a inner thread (not shown) or the like. 
     In  FIG. 2   b  is shown in a second stage where the filled second injection syringe  12  has been provided with the piston  23  with associated piston rod  24  for manoeuvring of the piston. After completed sterilization outside with a sterilizing gas, possibly when being packaged inside a gas penetrable plastic bag (not shown), the second injection syringe is ready for delivery/use. 
     It should be mentioned that other sterilizing methods for the liquid component are within the scope of the invention. Thus, depending on the material to sterilize, other per se known methods can be used such as radiation, sterilization with ionizing radiation or for example certain electromagnetic radiation with sufficient power for the application. Also for example autoclaving in moist heat can be used for certain applications. 
     In  FIGS. 3   a - f  are shown a sequence for conducting the mixing of the two components for achieving of an injectable mixture of, in the shown example, bone cement. 
       FIG. 3   a  shows the first  1  and the second  12  injection syringe taken out from their sterile packages and prepared for being connected through the first and second engagement means  8 ′ and  18 , respectively. These are here in the form of an outside thread  8 ′ outermost at the rotational portion  8  as concerns the first injection syringe  1  and said inner thread at  18  as concerns the second injection syringe  12 . The free holding means  28  shown in  FIG. 1   d  has already been removed from the first injection syringe  1  and left the channel inside the manoeuvring means  7 - 8  open for introduction of the liquid component  13 . 
     In  FIG. 3   b  is shown the second injection syringe  12  connected or docked to the first injection syringe  1 . In  FIG. 3   c  the process is illustrated with feeding of the liquid component  13  from the second  12  to the first  1  injection syringe through pressing-in of the piston  23 . 
     In  FIG. 3   d  is shown the mixing process, wherein the mixing element  4  is rotated at the same time as it is moved in axial direction of the cylinder  22  through actuation of the manoeuvring means  7 - 8 . At the end of this process, the mixture is de-aerated by a minor pressure being applied to the piston  20  over the piston rod  21  in order to create a minor over-pressure inside the cylinder  22  at the same time as the manoeuvring means  7 - 8  (with connected mixing element  4 ) is moved in the axial direction. During this important step of the method according to the invention, the completed mixture, which is put somewhat on over-pressure, is effectively de-aerated by gas enclosures in the mixture being “searched” by a mouth  24  to a de-aerating channel, which in this case is the said channel inside the manoeuvring means  7 - 8 . The de-aerating channel can also have more than one mouth  25 . 
     For example, the channel may have two mouths on opposite sides of the manoeuvring means  7 - 8 . Since the second injection syringe  12  is still connected to the first injection syringe  1 , captured, in many cases harmful gases, will be received inside the second injection syringe  12  such that they will not reach the operator&#39;s respiratory organs. 
     In  FIG. 3   e  is shown that after completed mixing, the manoeuvring means  7 - 8  for the mixing element  4  is released by simply pulling out the manoeuvring means  7 - 8  from the first injection syringe  1 . 
     It should been noted that in real life operation, the mixing element  4  can be invisible in some of the sequence steps above because of obscuring (bone cement) mixture. It is, however, for clarity shown throughout the Figures. 
     After that, as is shown on  FIG. 3   f , a chosen injection needle  26  is applied on the first injection syringe  1 , in this case with a connected finger grip  27 , whereupon the first injection syringe is ready for application of bone cement. 
     In a second embodiment, which is shown in  FIGS. 4-8  the system is somewhat modified. The first injection syringe  1 , which is shown in  FIG. 4   a , is provided with a mixing element  4  with a plurality (e.g., four) of mixing wings  4 ′ in the direction of the outlet of the syringe and, in the opposite direction, a plurality (e.g., four) of pins  4 ″ for providing a good mixing of the components. The detail  4 ″′ is a ring-shaped stabilizing element, which defines axial openings for allowing the mixing components easily to pass through the mixing element  4  during axial movements thereof. In the outlet end of the cylinder  22  is arranged a wiper plate  32 , which tightly lies against the tubular portion of the manoeuvring means  7 - 8  for the purpose of wiping off in particular pulverulent component  2  from this tubular portion when it is pulled in and out of the cylinder  22 . Hereby is avoided that the pulverulent material will reach out into the area of the outlet of the first injection syringe  1  and not being part of the mixing. Pulverulent material in this region would also unnecessarily increase friction between the tubular portion of the manoeuvring means  7 - 8  and the first injection syringe  1  in this area. 
     In  FIG. 4   b  is shown at the piston rod side of the first injection syringe  1 , a first grip  44 , which is rigidly fastenable to the first injection syringe  1 , and which has the function of facilitating handling, through a lock washer  46 , which can be snapped into a recess in the first grip  44  with radially outwardly extending wings (shown with full lines on the Figure), whereby the locking washer  46  lies in an axial direction against an end flange  45  on the first injection syringe  1 . 
     The first grip  44  has a portion at  50  for lying against a second side of this end flange  45 . The locking washer  46  further has portions (not shown) which extend radially inwardly inside the section of the cylinder  22 , such that they act like a stop and prevent the piston of the first injection syringe  1  from coming out of the cylinder  22 . Reference numeral  8  indicates a rotational portion for a manoeuvring means for the mixing element  4 . In  FIG. 4   c  is shown the first injection syringe  1  with removed free holding means  28  corresponding to what is described above in respect of the first embodiment. 
     In  FIG. 5   a  is shown an arrangement for filling the second injection syringe  12 , wherein it is docked to a first side of an adapter  33 , which on its other side, in a vial docking space, is arranged to receive a vial  34  with the liquid component  13 . It is further shown on  FIG. 5   a  a second grip  35  for the second injection syringe  12 , which grip in an axial direction from an outlet end towards a piston rod end lies against an end flange  51  ( FIG. 5   b ). The second grip  35  has a stop  36 , which outermost on the piston end side has a hook means  37  for engagement with an end side of a piston rod which is introducible into the second injection syringe  12 . The purpose of stop  36  is to avoid that during later use of the second injection syringe  12 , the piston contained therein is moved axially outwardly because of arising over-pressure, which is explained below. 
     As shown in  FIG. 5   b , the vial  34  is shown with an opening  39  after braking away of an enclosure end. Reference numeral  38  depicts a sealing/holding ring for ensuring holding of the vial  34  sealingly in position inside the adapter  33 . The adapter  33  further has a liquid filter  40  for filtering away impurities such as for example glass particles resulting from breaking of the opening end of the vial  34 . Further, the adapter  33  has a venting channel with a venting pipe  42 , which is arranged to be introduced somewhat into the vial  34  in its applied position. An air filter  41  is arranged in the venting channel for ensuring sterility of the air provided through the venting channel. 
     When using the adapter  33 , the stop  36  is released such that the second injection syringe  12  can be filled by axial pulling out of the piston in per se known manner until a predetermined amount of the liquid component  13  contained in the vial  34  has been drawn into the second injection syringe  12 . Thereupon, the second injection syringe is released from the adapter  33  preferably by screwing out of a threaded connection there between.  FIG. 5   c  shows the adapter  33  more clearly, freed from the vial  34  and from the second injection syringe  12 . At the side of docking with a second injection syringe  12 , is preferably arranged a thread (not shown) for secure mutual connection of these components. 
     In  FIG. 6  is shown the two injection syringes  1  and  12  docked to each other prior to feeding of the liquid component  13  from the second injection syringe  12  to the first injection syringe  1 . Hereby a piston rod of the second injection syringe  12  is thus pressed axially inwardly until it is locked by the axial stop  36  as is indicated above. During this inward pressure, an over-pressure will result in the connected unit, which would otherwise easily lead to a certain amount of liquid being fed back if the piston  23  would be allowed to move axially from the most inward position. This could give an erroneous mixing relation between the components and inferior properties of the mixture. In  FIG. 7  is shown an injection needle unit with an injection needle  26  for driving into bone as for example a vertebra of a patient, into which bone cement is to be injected. The injection needle  26  is shown with an insert point, which has good properties for allowing driving-in of the unit. Reference numeral  27  depicts a finger grip for the unit and reference numeral  49  depicts a press portion, with the aid of which the unit is applied and guided. In connection with the driving-in, the unit could be subjected to minor strikes in a driving direction, which most simply is conducted by removing the press portion  49  and application of strikes against a particular strike receiving element which can be screwed-in to the upper end of the unit. 
     In  FIG. 8  is shown the first injection syringe  1  in connection with on the one hand the manoeuvring means  7 - 8  for the mixing element  4  and the free holding means  28  which is introducible inside, and on the other hand with the injection needle unit with the injection needle  26  and removed insert point  48  as well as removed press portion  49 . The manoeuvring means  7 - 8  is shown with threads for engagement with the mixing element  4  but also other releasable connection can be used such as axial ridges in engagement with the grooves. 
     The invention can be modified within the scope of the following claims. The filling of the pulverulent component  2  and the liquid component  13  respectively can thus be made differently, even manually, even if automatic filling is preferred. Further, the docking means/engagement means can be constructed differently and gas transferring channels can be arranged differently from what is shown in  FIGS. 1   a - c . The gas transferring channel means for de-aerating can be separated from the shown manoeuvring means  7 - 8  for the mixing element, but it is highly preferred that these elements are integrated for simple function and good economy. 
     The separate reservoir is preferably included, which is described above, in a second piston cylinder arrangement and preferably it is in form of an injection needle. It is, however, also within the scope of the invention, that the separate reservoir is of a different construction, for example a breakable ampoule or without means for pressurizing the liquid component. In one embodiment the separate reservoir, which can be or include such an ampoule, is on one side possible to dock to the first injection syringe  1  and on a second side connected or connectable to a piston cylinder device or any other pressure creating device for driving purposes, whereby can be created an over-pressure such that the liquid component can be introduced into the first cylinder of the first injection syringe  1 . In a further embodiment can be provided an under-pressure in the cylinder of the first injection syringe  1 , whereby can be initiated that the liquid component  13  can be sucked into this cylinder. 
     The invention can be used in respect of other mixtures for medical purposes but is preferred in more highly viscous or paste-like mixtures such as bone replacement material or bone cement, even if it is not excluded that the invention is also applicable in more low viscous mixtures with the property of binding air enclosures and therefore should be de-aerated. 
     For other mixtures that can come into question for the using of a system according to the invention, other sterilizing methods than the above described can come into question. A pulverulent component  2  can for example be sterilized in dry hot atmosphere and a liquid in moist hot atmosphere. 
     The invention can be modified further and one example of that is that it can be given an indication on when the mixture is completed and as an example also has reached a certain viscosity by using a coupling between the manoeuvring means and the mixing element, which releases from rotation upon reaching a certain viscosity and corresponding rotational resistant of the mixture.