Patent Publication Number: US-2010114067-A1

Title: Multi-Chamber Mixing System

Description:
FIELD OF THE INVENTION 
     This invention is related to mixing systems for storing and mixing individual components of medical compositions and administering these compositions to patients. More particularly, this invention is related to mixing systems with multiple, isolated chambers. 
     BACKGROUND 
     Various medical compositions, such as bone fillers, bone cements, and dental and medical adhesives, often require combining together several components in liquid or solid form. Typically, the individual components of such compositions are separated from each other during storage and are combined immediately prior to their administration to a patient. 
     To be successful a system for storing and mixing individual components for medical compositions needs to meet a number of objectives. First, it needs to be capable of storing components in both liquid and solid form and to ensure that these components are completely isolated from each other during storage and transportation of the mixing system. Second, a mixing system needs to enable mixing of the individual components that is rapid and thorough and requires minimum effort by the user. Third, although many separate components may be involved, a mixing system needs to be designed in such a way as to minimize its size in order to facilitate convenient handling, transportation and storage of the mixing system. 
     Although many different mixing systems are currently available, none of them meets all of these objectives. Accordingly, there is still a need in the art for an improved mixing system for mixing medical compositions and administering them to a patient. 
     SUMMARY 
     Mixing systems for storing and mixing components for multi-component medical compositions are provided. 
     In one embodiment, a multiple-component mixing system may comprise a first barrel comprising at least one first chamber, a plunger slidably disposed inside the barrel, at least one second chamber disposed inside the plunger and fluidly isolated from the at least one first chamber; and a pushing rod disposed inside the plunger proximally of the at least one second chamber. 
     In another embodiment, a multiple-component mixing system may comprise a barrel comprising at least one first chamber and at least one second chamber fluidly isolated from each other, a plunger slidably disposed inside the barrel, at least one third chamber disposed inside the plunger and fluidly isolated from the at least one first chamber and the at least one second chamber, and a pushing rod disposed inside the plunger. The second chamber may be disposed between the plunger and inner walls of the barrel. 
     In yet another embodiment, a multiple-component mixing system may comprise a first barrel and a second barrel fluidly connected to a common outlet. Furthermore, at least one of the barrels may comprise at least one first chamber, a plunger slidably disposed inside at least one of the barrels, at least one second chamber disposed inside the plunger and fluidly isolated from the at least one first chamber, and a pushing rod disposed inside the plunger proximally of the at least one second chamber. The barrel with multiple chambers may further include at least one third chamber formed between the interior wall of the barrel and the outer wall of the plunger. 
     In yet another embodiment, the invention provides a method of mixing multiple-components in the same device in which they were stored and delivering the mixed multi-component composition to a target site. 
     In all aspects, the pushing rod is preferably adapted to push a component from the chamber inside the plunger into a chamber in the barrel. Accordingly, each chamber in the instant mixing system may be used for storing individual components in various forms such as liquid, solid, or powder. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1  presents one embodiment of the instant multiple component mixing system. 
         FIGS. 2-5  present use of one embodiment of the mixing system of  FIG. 1 . 
         FIGS. 5-7  present use of another embodiment of the mixing system of  FIG. 1 . 
         FIGS. 8-9  present one embodiment of a closable mixing channel of the mixing system of  FIGS. 5-7 . 
         FIG. 10  presents another embodiment of the instant multiple component mixing system. 
         FIGS. 11-13  present use of the mixing system of  FIG. 10 . 
         FIG. 14  presents yet another embodiment of the instant multiple component mixing system. 
     
    
    
     DETAILED DESCRIPTION 
     Mixing systems for storing and mixing multiple components of various medical compositions are provided. In particular, such systems may be used for administering bone cements in orthopedic procedures, such as for anchoring artificial joints, or in spine related procedures, such as the treatment of vertebral compression fractures and traumatic reconstructions. 
     Generally, the instant mixing systems comprise a barrel, a plunger slidably disposed inside a barrel, and a pushing rod slidably disposed inside the plunger. The instant mixing system may further comprise multiple chambers for storing individual components or mixtures of components, with at least one chamber disposed in the barrel and at least one chamber disposed inside the plunger. The total volume of the instant mixing system could feasibly be between about 5 cc to about 50 cc. The volume of individual chambers within the instant mixing system may range between about 1 cc to about 20 cc. 
       FIG. 1  presents one embodiment of the instant multiple-component mixing, dispensing and/or injecting system. Such mixing and dispensing system  10  comprises a barrel  12  having a distal end  13 , a proximal end  14 , side walls  15 , distal walls  16 , and, optionally, proximal walls  17 . A nozzle  18 , disposed at the distal end  13  of the barrel  12 , facilitates attachment to the barrel  12  of a needle, a catheter or any other devices through which the contents of the mixing system may be administered to a patient. 
     A plunger  19  is slidably disposed inside the barrel  12 . The plunger  19  comprises a generally cylindrical hollow plunger shaft  20  with side walls  20   a,    20   b  and a plunger cap  21 , preferably, sized to form a seal with the interior walls of the barrel  12 . In some embodiments, the outer diameter of plunger shaft  20  may be approximately the same as the inner diameter of the barrel  12  so a seal is formed between the plunger  19  and the barrel  12  to prevent components inside the barrel from spilling out, and thus the proximal walls of the barrel  12  may be omitted. Alternatively, the outer diameter of the plunger shaft  20  may be smaller than the inner diameter of the barrel  12  to define an additional chamber, and thus the proximal walls may be needed, unless the additional chamber is sealed by other means. The plunger cap  21  comprises a central opening  22 , a proximal side  23   a  and a distal side  23   b.  Initially, the central opening  22  may be by sealed by means of a frangible seal  24 . As used herein, the term frangible seal means a seal that has sufficient integrity to avoid breakage during storage and normal handling, but that can be intentionally separated or ruptured when desired without undue effort and without creating particulates that may be harmful to a patient. Suitable materials for the frangible seal may include, but are not limited to, rubber, silicone, polyurethane, or Teflon. 
     A pushing rod  25  having a distal end  26  may be disposed within the plunger  19 . The pushing rod  25  is preferably sized so at least the distal region  27  of the pushing rod  25  forms a tight seal with the interior walls of the plunger and fits tightly into the central opening  22  in the plunger cap  21 . The pushing rod  25  is adapted to push the material from the chamber inside the plunger. For example, the pushing rod may comprise at least one section that is sized to form a seal between the pushing rod and the plunger distally of the chamber inside the plunger. 
     The multiple-component mixing system  10  may comprise multiple chambers for storing individual components. At least one chamber, such as a first chamber  28 , may be situated in the distal region  29  of the barrel  12 . Such first chamber may be defined by side walls  15  and distal walls  16  of the barrel  12  and the distal side  23   b  of the plunger cap  21 . The first chamber  28  may contain at least one component, such as a first component  30  either in solid, powder, or liquid form. The first component may comprise a single component or a mixture of components. In addition, at least one chamber, such as a second chamber  31 , may be located in the distal region  32  of the plunger  19 . Such second chamber may be defined by the interior walls of the plunger  19 , the distal end of the pushing rod  25 , and the proximal side of the plunger. The second chamber  31  may hold a single component or a mixture of components, such as a second component  33 , either in solid, powder, or liquid form. 
       FIG. 1  shows an embodiment of the instant multi-component mixing system in its initial state, such as storage or transportation. In the initial state, the first chamber  28  and the second chamber  31  are isolated from each other and are filled with the first component  30  and the second component  33 , respectively. As shown in  FIG. 2 , to add the second component  32  to the first chamber  28 , the pushing rod  25  may be moved in the distal direction, which is indicated by arrow A. Moving the pushing rod  25  in the distal direction generates a force in the distal direction on the second component  33  causing the frangible seal  24  to break and to release the second component  33  into the first chamber  28 . Accordingly, as noted above, the distal region  27  of the pushing rod  25  preferably forms a tight seal with the interior walls of the plunger shaft  20  to prevent the second component  33  from traveling in the proximal direction into the space between the plunger and the pushing rod. 
     Once the second component  33  is added to the first chamber  28 , the first component  30  and the second component  33  may be mixed by any known technique. In one embodiment, the first and second component may be mixed inside the first chamber  28 . For example, as shown in  FIG. 3 , the pushing rod  25  may extend past the plunger cap  21  into the first chamber  28 , and the first and second components may be mixed by oscillating or spinning the pushing rod  25 . To aid mixing of the components, the pushing rod  25  may comprise a mixing section  25   a  disposed in the distal region  27  of the pushing rod  25 , such as, for example, sections with varying diameters, as shown in  FIG. 3   a,  or similar. Alternatively, the first component may be mixed with the second component by shaking or vibrating the mixing system. 
     Referring to  FIG. 4 , once the components are sufficiently mixed to result in a uniform mixture  40 , the pushing rod  25  may be withdrawn back into the plunger  19 , preferably aligning the distal end  26  of the pushing rod  25  with the distal side  23   b  of the plunger cap  23  to form a continuous surface  34  on the distal side  23   b  of the plunger cap  23 . Accordingly, it is desirable that the distal region of the pushing rod  25  is sized to form a tight seal with the central opening to prevent the component mixture from flowing into the plunger. In some embodiments, the pushing rod  25  may be locked in that position by a lock  38 . 
     In another embodiment, the mixing system  10  may include at least one mixing chamber, such as the first mixing chamber  35 , for mixing individual components. In such embodiment, the outer diameter of the plunger shaft  20  is smaller than the inner diameter of the barrel  12 , so the first mixing chamber  35  is formed between the inner walls of the barrel  12  and the outer wall of the plunger shaft  20 . Additionally, in such embodiments, the plunger cap  21  may include at least one mixing channel, such as a first mixing channel  36 , to allow the components to flow from the first chamber  28  to the mixing chamber  35 . Preferably, the first mixing channel  36  includes a mixing element  37  to achieve better mixing of the components. Suitable examples of the mixing element include, but are not limited, to a static mixer with a range of mixing elements, sizes, and shapes or a rotating or exposed impeller. Operation of this embodiment of the mixing system is shown in  FIGS. 5-7 . 
     Referring to  FIG. 5 , after the second component  33  is added to the first component  30 , the pushing rod  25  may be inserted into the central opening  22  of the plunger cap  21  to plug the central opening  22 , as described above. In some embodiment, the pushing rod may be locked in this position by the lock  38 . 
     Next, the plunger  19  and the pushing rod assembly  39  is moved in the proximal direction toward the distal end  13  of the barrel  12 , as shown in  FIG. 6 . The plunger and the pushing rod assembly  39  may be moved manually, with a ratchet, or a syringe pump. Because the nozzle  18  is preferably sealed during mixing, moving the plunger and pushing rod assembly  39  in the distal direction forces the first component  30  and the second component  33  to flow from the first chamber  28  through the mixing channel  36  into the first mixing chamber  35 . Once the components are transferred from the first chamber  28  into the first mixing chamber  35 , the plunger and the mixing rod assembly  39  is moved back in the proximal direction. This forces the mixture of components  40  to flow back from the first mixing chamber  36  into the first chamber  28 , as shown in  FIG. 7 . The steps shown in  FIGS. 5  though  7  may be repeated to further mix the components as necessary or desired. 
     To extrude the mixture of components  40 , the first mixing channel  36  is preferably closed. For example, referring to  FIG. 8 , the distal side  23   b  of the plunger cap  21  may be rotatable relative to the proximal side  23   a  and may include at least one opening  41 . To open the first mixing channel, the at least one opening  41  in the distal side  23   b  of the plunger cap  21  may be aligned with the first mixing channel  36 . Referring to  FIG. 9 , to close the first mixing channel  36 , the distal side  23   b  may be rotated by, for example, rotating the plunger shaft  20  as represented by arrow B, so the at least one opening  41  in the distal side  23   b  of the plunger cap  21  no longer aligns with the first mixing channel  36 , thus closing the first mixing channel  36 . However, the channels may not need to be closed if, when the mixture is pushed in the distal direction, it is more likely to flow out from the mixing system than into the mixing chamber. 
     Referring back to  FIG. 7 , once the first component and the second component are sufficiently mixed to form the mixture  40 , the plunger and the pushing rod assembly  39  may be moved in the distal direction, as shown by arrow C, to force the mixture of components  40  out of the barrel  12  through the nozzle  18  and into a syringe, a catheter, or any other device for administering the mixture from the mixing system to a patient. In some embodiments, the nozzle may be sealed with a frangible seal. Such seal is preferably designed to withstand the pressure generated when the components are being mixed and to break due to pressure generated when the mixture is being extruded out of the barrel. In other embodiments, the nozzle may be closed by mechanical means such as a lid or a cap. 
     In another aspect, the instant mixing system may include more than two chambers and, thus, may be used to prepare mixtures requiring more than two components. In particular, the instant mixing systems may be used to prepare epoxy-like materials that have more than one liquid part, and may require the separate storage of a powdered or dry initiator for polymerization. 
     One embodiment of the instant mixing system comprising more than two chambers is presented in  FIG. 10 . Such system is similar to the embodiments described above, except that in addition to the at least one chamber in the distal region of the barrel and at least one chamber in the distal region of the plunger, it may also include at least one additional chamber located between the walls of the barrel and the plunger. For example, the additional chamber may be defined by the inner wall of the barrel, the proximal wall of the barrel, the outer wall of the plunger, and the proximal side of the plunger cap. 
     Referring to  FIG. 10 , the multiple-component mixing system  100  comprises a barrel  102  having a distal end  103 , a proximal end  104 , side walls  105 , distal walls  106 , and optionally proximal walls  107 . A nozzle  108 , disposed at the distal end  103  of the barrel  102 , facilitates attachment to the barrel  102  of a needle, a catheter or other devices through which the contents of the mixing system may be administered. 
     A plunger  109  is slidably disposed inside the barrel  102 . The plunger  109  comprises a generally cylindrical hollow plunger shaft  110  with side walls  110   a,    110   b  and a plunger cap  111 , preferably, sized to form a seal with the interior walls of the barrel  102 . The outer diameter of at least one section of the plunger shaft  110  is smaller than the inner diameter of the barrel  102  to accommodate a chamber, and thus the proximal walls  107  of the barrel  102  seal the chamber at its proximal end, unless the chamber is sealed by other means. The plunger cap  111  comprises a central opening  112 , a proximal side  113   a  and a distal side  113   b.  Initially, the central opening  112  may be by sealed by means of a frangible seal  114 , as defined above. 
     A pushing rod  115  having a distal end  116  may be disposed within the plunger  119 . The distal end of the pushing rod  115  preferably fits tightly into the central opening  112  in the plunger cap  111  to form a seal. The pushing rod  115  is adapted to push the material from the chamber inside the plunger. For example, the pushing rod may comprise at least one section that is sized to form a seal between the pushing rod and the plunger distally of the chamber inside the plunger. 
     The multiple-component mixing system  100  may comprise multiple chambers for storing individual components. The chambers are isolated from each other during storage and transportation of the mixing systems. Each chamber may store a single component or a mixture of components in either in solid, powder, or liquid form. At least one chamber, such as a first chamber  118 , may be situated in the distal region  119  of the barrel  102  defined by side walls  105  and distal walls  106  of the barrel  102  and the distal side  113   b  of the plunger cap  111 . At least one additional chamber, such as a second chamber  120 , may be located proximally of the first chamber  118  between the inner walls of the barrel  102  and outer wall of the plunger shaft  110 . Yet another chamber, such as a third chamber  121 , may be located in the distal region  122  of the plunger  109 . In the preferred embodiments, the third chamber may be defined by the interior walls of the plunger  109 , the proximal side of the plunger cap  113   a  and the distal end of the pushing rod  116 . Alternatively, the pushing rod may have a section with the smaller diameter than the inner diameter of the plunger, and the third chamber may be disposed between the pushing rod and the wall of the plunger along such section. However, it is desirable that the diameter of the pushing rod proximally of the third chamber is selected so the pushing rod and the interior walls of the plunger form a tight seal proximally of the third chamber. 
     The plunger cap  113  may include at least one channel  124  between the first chamber  118  and the second chamber  120 . The at least one channel  124  may be open and closed as described above in regard to the mixing chambers and shown in  FIGS. 8 and 9 . Alternatively, the at least one channel may include check valves that permit flow from the second chamber to the first chamber but not the other way. To achieve more thorough mixing, the at least one mixing channel  124  may comprise a mixing element  125 . 
       FIG. 10  shows the multi-component mixing system in its initial state, such as storage or transportation. In this state, the first chamber  118 , the second chamber  120 , and the third chamber  121  are isolated from each other and are filled with the first component  126 , the second component  127 , and the third component  128 , respectively. Referring to  FIG. 11 , to add the third component  128  to the first chamber  118 , the pushing rod  115  may be moved in the distal direction, as indicated by arrow D. To add the second component  127  to the first chamber  118 , the plunger  109  may be moved in the proximal direction, as shown in  FIG. 12 , or in the distal direction. Alternatively, in embodiments without check valves, the components in the first chamber may be mixed with components in the second chamber by moving the plunger in the distal direction, as shown in  FIG. 13 . 
     Next, the components are mixed so the mixture may be administered to a patient. In some embodiments, all components may be collected in the same chamber and then mixed in a single step. In other embodiments, select components may be mixed first with the other components added to the mixture at a later time. The mixing may be achieved in a variety of ways depending on the embodiment of the mixing system, the sequence of mixing and so forth. For example, if the individual components need to be mixed in the first chamber, such as if the first and second component need to be pre-mixed prior to addition of the third component or in the embodiments with the check valves, the components may be mixed with the assistance of the pushing rod as described above. Alternatively, in the embodiments without the check valves, the third chamber may be used as the mixing chamber as described above and is shown in  FIGS. 5-7 . 
     Once all components are sufficiently mixed, the pushing rod is withdrawn into the plunger, as described above, and the plunger and the pushing rod assembly may be moved in the distal direction to force the mixture of component out of the barrel through the nozzle to be administered to a patient. In the embodiments without check valves, the channels are preferably closed as described above. 
     Another embodiment of the instant mixing system comprising more than two chambers is presented in  FIG. 14 . In this embodiment, the mixing system  200  comprises multiple barrels, such as the first barrel  202  and the second barrel  204 . At least one of the barrels may comprise two chambers or more than two chambers, as described above. Although  FIG. 14  shows the multiple-component mixing systems comprising of two barrels with only one of the barrels comprising two chambers, it will be understood that in various embodiments more than two barrels may be employed and any number of the barrels may comprise two chambers or more than two chambers. 
     The first barrel  202  and the second barrel  204  are connected to the common outlet  206 . The common outlet  206  may include a static mixer  208  to achieve better mixing of components or mixtures of components from various barrels. In practice, if a barrel holds multiple components, these components may be mixed within that barrel by any method described above and the resulting mixture may then be mixed with contents of other barrels. In some embodiments including more than two barrels, all barrels may be connected to the same common outlet so their contents may be mixed at the same time. In other embodiments, the contents of select barrels may be mixed first and the contents of other barrels may be added at a later time. 
     The instant mixing systems allow mixing multiple components together within a single device. By way of non-limiting example, some in situ curing formulations comprising at least two liquid components may have stability issues, which may cause the individual components to separate when administered to a patient. If the individual components separate, the formulation may only partially cure or not cure at all, and additional amounts of the formulation may have to be administered to the patient, thus increasing the cost and duration of the medical procedure. Hence, there may be a need to mix a stabilizing component, usually in the form of powder, with one liquid component prior to mixing the liquid components together. 
     Accordingly, the first liquid component and the second liquid component may be stored in the first chamber and second chamber, respectively, of the instant mixing system. The stabilizing component in the form of powder may be stored in the third chamber inside the plunger. To prepare the formulation, the stabilizing component may be added to the first chamber and thoroughly mixed with the first liquid component, as described above. Then, the mixture of the first liquid component and the stabilizing component may then be mixed with the second liquid component, as described above, to produce a stable liquid formulation. 
     Note that the specifics embodiments are described in an exemplary manner and are not intended to limit the invention. In particular, mixing systems manufactured of any acceptable material are contemplated to be within the scope of the invention, as are mixing systems having varying design configurations and numbers of chambers. The scope of the invention is therefore defined in the claims which follow.