DE20005333U1 - Preparation and application device for implant materials - Google Patents

Description

ZENZ ■ HELBER ■ HOSBACH & PARTNER

Patent Attorneys · European Patent Attorneys · 64673 Zwingenberg,

Scheuergasse 24

Tel.: 06251-73008 · Fax: 06251-73156

Coripharm Medical Products GmbH & Co. KG
Lagerstr. 11-15, 64807 Dieburg

Preparation and application device for implant materials

The invention relates to a preparation and application device for implant materials consisting of at least one powdered or granular component and one liquid component, which are to be prepared immediately before use, with a first container which holds the powdered or granular component in a sterile manner and a second container which holds the liquid component in a sterile manner and which can be connected to the first container, wherein means for producing an overflow connection between

&iacgr;&ogr; the containers, to displace the liquid component from the second in

the first container and for intimate homogeneous mixing of the components in the first container by movement of a mixing element arranged in the first container and arranged on a mixing shaft which leads out of the container in a sealed manner, and the first container is designed to be connectable to a vacuum source.

In recent years, minimally invasive treatment methods have become increasingly popular in the surgical treatment of defects in the skeletal system. In particular, in orthopedics and trauma surgery, methods are used in which the treatment itself is carried out, sometimes under X-ray control, e.g. only through puncture incisions or percutaneously. The advantage of these methods compared to conservative, open surgery is obvious: the procedure is far less stressful for the patient, hospital stays are significantly shortened and treatment costs are therefore significantly reduced. In addition, the risk of infection is much lower, so that long-term and costly complications can be avoided.

Especially in the reconstructive treatment of bone defects, fillers, stabilisers, auxiliary agents and/or active substances are delivered percutaneously directly to the site of the defect during minimally invasive treatment. They are used there in particular to fill the defect and partially stabilise it, as well as to stimulate repair processes, induce and accelerate neovascularisation and new bone formation, and to prevent and/or treat infections in the defect area. Most of the substances used in this process are

0 However, the materials or active ingredients, or their combinations, cannot be applied with conventional injection syringes due to their special composition and the resulting consistency. Instead, it is necessary to use special applicators that are specifically adapted to the respective product in order to bring the therapeutic agents, i.e. the implant materials, to the place of application easily and safely.

Of course, it is necessary to bring together the implant materials, which usually consist of different individual components, and mix them into a homogeneous matrix before application.

However, it has been shown that the chemical and physical properties of the implants, and in particular their mechanical strength - important prerequisites for the optimal performance of their tasks - are significantly influenced by the type and manner of the mixing process carried out.

This is made clear using the example of the implant material bone cement, where these influences have been intensively investigated:

It has been known for several years that the mechanical properties of bone cements are significantly reduced by larger and smaller air inclusions that enter the resulting cement matrix, particularly when the cement components are mixed. This weakening of the cement is easily measured and proven physically, and it is understandable when one considers that, particularly when the components are mixed incorrectly by hand, the cement matrix can contain up to 25% air. These air bubbles trapped in the cement create pores that lead to cracks and fissures in the cement when the prosthesis is later loaded. This in turn causes premature disruption of the cement mantle surrounding the prosthesis, which leads to loosening of the prosthesis and the need for the prosthesis to be removed. Conversely, experimental and clinical studies have shown that cements that are almost air-free and therefore pore-free contribute to greater fatigue resistance and thus to an extension of the service life of endoprostheses.

In addition to this example from the field of bone cement, reference should be made to technical processes in ceramic production. Here too, the state of the art, especially when processing high-quality plasters and impression materials, is to produce pore-free (i.e. air-free) matrices in order to achieve the necessary mechanical strength of the end product.

Reach 0.

The same requirements must also be met for medical implant materials such as those based on calcium phosphates, calcium sulfates or certain polymers, which have a stabilizing function in addition to their physiological effect. Air inclusions must also be avoided when preparing and mixing these products in order to ensure the desired mechanical strength in the end product of the implant material.

While the technical field has been doing this for a long time, there are still no corresponding

Mixing and/or application systems for ceramic implant materials, for example. In the case of bone cements, the recognition of this problem has led to intensive work on mixing systems in recent years, with the aim of developing processes that make it possible to largely avoid air inclusions in the cement when mixing the cement components, and to develop mixing methods that ensure reproducible and standardized mixing results.

Again, using the example of very well-researched bone cements, this

0 development: The result of intensive efforts led

to the so-called "vacuum mixing technology" which is now generally accepted and regarded as state of the art, in which the mixing of the cement components (polymer powder and monomer liquid) is carried out in particularly suitable and specially designed mixing vessels or application cartridges under reduced atmospheric pressure.

In order to achieve a "vacuum" (a reduced air pressure) that reduces the air content in the ready-mixed cement matrix to a minimum, residual pressures of approx. 100 to 200 mbar must be maintained during the mixing process.

&ogr; can be ensured.

t · · t · 1

In practice, this involves sealing the cement mixing vessel tightly after filling it with the cement components and connecting it to a pump driven by compressed air via a hose. Depending on the compressed air source and pump design, the amount of air contained in the mixing system is reduced - more or less quickly - so that more or less low residual pressures result, although not every system on the market is able to reduce the air pressure so far that the goal - an almost pore-free cement - is actually achieved in practice.

A very significant problem with this type of "vacuum mixing" of bone cement is that, in addition to the very different pump performances, the hospital's own compressed air supply in the operating room, which is required to operate the pumps, is subject to very large fluctuations. For example, the in-house compressed air in different hospitals may vary not only depending on the time of day but often generally between initial pressures of approx. 5 to approx. 10 bar, which of course significantly influences the pump performance and thus the "vacuum" in the mixing vessels and, as a result, the cement quality with regard to air inclusions. Standardizable and reproducible mixing results cannot be achieved in this way.

Furthermore, only some of the pumps used today have a pressure gauge that displays the pump output and monitors it during the mixing process. However, these measuring devices on the pumps themselves do not necessarily reflect the pressure conditions in the actual mixing vessels.

5 It is important to ensure that the residual pressure in the mixing vessel is monitored during

The entire duration of the mixing process is an absolute prerequisite for an adequate, reliable mixing result. In all known "vacuum" mixing systems, suitable display or measuring devices are actually missing on the mixing vessels themselves, so that it cannot be guaranteed that in the

0 Mixing vessel before and/or during the actual mixing process of the At-

atmospheric pressure was actually reduced to the residual pressure necessary for the mixing result - namely a largely pore-free cement.

This results in significant disadvantages for the procedures currently used and considerable risks for the quality of the cement and thus for the long-term clinical success of the artificial joint replacement.

In addition, more and more clinics are now switching to electrically powered surgical devices, so that there is no longer any suitable compressed air connection available in the operating room.

In order to exclude these sources of error and imponderables, as described in the example of the "vacuum mixing" of bone cements, but also in order to put the production of pore-free matrices into practice for other implant materials, apart from bone cements, as are increasingly used in reconstructive surgery, the aim of this invention was to develop a versatile, simple and safe to use method.

0 to create a mixing and application system that is suitable for optimizing the preparation of implant materials to be introduced into the human and/or animal body with regard to their chemical and physical properties. Important indications for such a system can be found in particular in the field of orthopedics and trauma surgery.

When implementing this task technically, it was necessary to take two essential aspects into account.

1. The system according to the invention is intended to ensure the production of largely pore-free implant materials and, except for polymers, in particular

&ogr; especially suitable for ceramic materials in the broadest sense.

■*

2. The system according to the invention should enable the simple and safe combination of the components required to produce the implant material. The entire process of combining and mixing the components should take place under sterile conditions and hermetically sealed so that no contact between the components and the outside air is possible.

The problem of producing pore-free (i.e. air-free) matrices will be illustrated using bone cement as an example. This problem is general and also applies to the mixing and application of other types of implant materials. However, it has been thoroughly investigated and documented in the field of bone cement in recent years, which is why reference is made to this sector. As described, experimental and clinical studies have shown that the conventional mixing of cement components, e.g. using simple, key-shaped containers and a spatula, is not only laborious and problematic from an aseptic point of view, but that this technique in particular introduces a great deal of air into the cement dough in the form of larger and smaller bubbles. These inclusions reduce the mechanical strength of the

0 hardened cement, especially its "fatigue resistance" significantly

and thus lead to premature failure of the prosthesis function.

The so-called open mixing - as described - also has other practical disadvantages. Since the packaging of the cements is usually in a

5 bags for the powder and a glass jar for the liquid,

It is very easy to spill powder or liquid when pouring the components into the mixing vessel. However, the precisely coordinated ratio of powder to liquid quantity required for perfect polymerization is then no longer guaranteed, which also affects the mechanical properties of the

0 properties of the finished cement can be negatively influenced.

Furthermore, the open handling of the components means that the powder causes a lot of dust to be generated when it is poured out and that monomer vapors escape from the liquid into the breathing air and can pose a health risk - in particular allergic reactions - to the operating room staff involved in the mixing.

Many of the problems mentioned also apply to the processing of other implant materials.

&iacgr;&ogr; All these negative experiences have led to the fact that over the last

Years of mixing procedures have been developed with the aim of avoiding the sources of error mentioned above.

For example, mixing vessels have been developed in which the container is tightly closed after the components have been added so that no monomer vapors can escape during the mixing process.

In other systems, the mixing process takes place after the mixing vessel has been charged under reduced atmospheric pressure.

0 The monomer vapors are extracted using a "vacuum pump" and bound in a carbon filter.

Recently, mixing systems have become known in which polymer powder and monomer liquid are already present in parts of the mixing system from the manufacturer. The two components are filled into separate containers, but these can be connected to one another. This is intended to ensure that the mixing process can be carried out without external influences or interference. Examples of such systems are described in the applications US 4,277,184, US 5,328,262, US 5,549,380, US

0 5,551,778, DE 40 30 832 and EP 0 692 229.

However, in practical production and application, these systems still have significant deficiencies and disadvantages. In particular, the sterile production of such packaging units is a major problem. Basically, only three processes are possible for the sterilization of bone cements: For the monomer, sterile filtration and sterile filling. For the polymer, γ-ray sterilization or ethylene gassing.

Since the container for the polymer powder in the known systems must be hermetically sealed to ensure sterility, these powder containers are usually subjected to γ-irradiation for sterilization. However, as recent studies have shown (HARPER et al., J. of Mat. Sci.: Mat. in Med. 8, 849-853, 1997), treating the cement powder with high-energy radiation leads to a significant deterioration in the mechanical strength of the cement and to an increased risk of premature mechanical loosening of the prosthesis. Of course, a mixed system in which the containers for polymer and monomer are connected to one another cannot be subjected to γ-irradiation because this would lead to premature polymerization of the monomer.

0 In principle, however, a system that reliably avoids the disadvantages of the existing devices described above and, in addition, is particularly useful for the predominantly ceramic implant materials (except bone cements), which are becoming increasingly important today and for which pore-free production is also of crucial importance, would be of great benefit, since

5 it would significantly simplify the handling of implant materials in the operating room, but above all it would also make it safer in every respect.

There is therefore a need to find a solution to the problem that is uniform for the various implant materials in use today.

0 stranded and where on the one hand the advantages of providing

hermetically sealed, pre-filled, sterile components offers

be used, but which on the other hand reliably avoids the disadvantages and clinical safety risks that exist with conventional systems, whereby a mixing system that is completely free from external conditions and influences and can be operated absolutely independently of the clinical requirements regarding the presence of a compressed air supply or an electrical energy source that is suitable in terms of quantity per minute and level of the output pressure would be particularly advantageous. In addition, it seems expedient to integrate the "vacuum source" directly into the mixing system in order to ensure that mixing can be handled easily and safely and, in particular, to be free of annoying hose connections that interfere with the operation of the system, since it has been shown that this repeatedly causes breakdowns in practice and that conventional pump systems are unwieldy and cumbersome to use and are difficult to sterilize and maintain. In addition, the new mixing system should be designed in such a way that the residual pressure in the mixing vessel itself can be continuously monitored during the entire mixing process.

In the context of minimally invasive procedures, which are very advantageous for many reasons and are increasingly preferred today in the treatment of bone

0 defects, the applicable

Implant materials are preferably used locally, directly at the site of the defect.

However, it has been shown that the injection of liquid implant materials and/or active substances is unsuitable and not very useful, particularly in the treatment of bone defects such as fractures, pseudoarthroses and cysts. Instead, the implants must be applied in a consistency that ensures that they remain locally, at the target site, for a longer period of time and can thus initiate the biological reconstruction processes. In addition, implant materials must be taken into account.

0, which solidify on site, have to fulfil certain supporting and stabilising functions and can also serve as active ingredient carriers.

This goal can be achieved in a particularly advantageous manner by administering the implant materials either in the form of a paste or by administering active ingredients as part of a viscous matrix. It is particularly advantageous if the matrix solidifies on site within a certain, not too long period of time, so that the implant, possibly consisting of carrier materials and active ingredients, is available at the site of the defect for a longer period of time. It is desirable, however, that the applied matrix is degradable and/or absorbable, so that after a certain period of time, the defects initially filled and stabilized by the matrix are filled with newly formed bone, thus fully restoring the original physiological and biological condition of the affected skeletal section and ensuring full load-bearing capacity.

Such pasty or viscous implants, which may harden locally, often necessarily consist of two or more components, which are initially separate and can only be applied after they have been brought together and mixed. Such systems usually consist of a dry, powdery component and a second liquid component. The powders can be individual components or combinations of, for example:

Hydroxylapatite, tricalcium phosphate, calcium sulfate, calcium carbonate, polymers, in particular those based on polyacrylates and/or polymethacrylates, as well as lactide, glycolide and/or lactide/glycolide, collagen, polysaccharides such as agarose, gelatin, fibrin or the like. The corresponding liquids are in particular those on a water basis (such as e.g.

Water (aqua pro injectione), buffer solutions, Ringer's solution, physiological saline solution, blood, serum, etc.) or suitable organic liquids such as monomer liquids. Of course, it is necessary to combine the individual components before application and to form a

0 homogeneous, pore-free matrix. For this process,

conventional mixing processes, such as those used in the field of bone cement

elements or from the mixing and processing of ceramic materials.

For the handling of such systems, including the sterile, simple and safe local application of the implant material immediately after it has been mixed, it is very advantageous to have the sterile powder component in a hermetically sealed container, possibly equipped as a mixing system, and to have the sterile liquid in a separate, hermetically sealed container. Both containers must be in sterile double packaging, as is the case for containers used in the operating room.

materials are available. After removing the containers from the packaging, the components contained in the two containers must be combined, mixed and applied under sterile conditions.

Based on the above statements and the clinical-therapeutic problems and requirements described, the object of the present invention is to find a simple and safe solution for bringing together implant components, as well as to solve the problem of designing the "vacuum", mixing and storage units in such a way that the

0 entire system at the same time also for the homogeneous mixing of the contents if necessary.

under reduced atmospheric pressure and for the subsequent application of the mixture into the bone defect. In particular, the liquid injector (see below) should be designed so that it contains organic solvents, such as a monomer such as methyl acrylate / methyl methacrylate.

5 should be designed so that it is absolutely leak-proof in order to ensure that the monomer can be stored for a long time without any loss of substance, which experience has shown cannot be achieved using a piston. The liquid injector should also be suitable for taking up viscous materials or suspensions.

Starting from a device of the type mentioned at the outset, this object is achieved according to the invention in that the mixing shaft which is led out of the first container in a sealed manner is hollow and is connected at its outer end to a hand pump for generating the negative pressure and is connected to the hand pump, that the hollow mixing shaft is provided with a through-opening in the area which is led through the container wall in a sealed manner in the fully inserted position, which is connected to a passage channel which opens into the container wall in this area, is provided with a self-closing valve and leads into the interior of the container, that a measuring device which indicates the negative pressure prevailing in the container can be connected to the first container, and that the housing of the hand pump is designed to be suitable as a handle for moving the mixing shaft.

This design ensures that the sterile ingredients contained in the separate hermetically sealed containers can be combined under sterile conditions without the contents of the containers coming into contact with the outside air. This is achieved in particular by the connection module used, i.e. the perforation cylinder, which

0 when assembling the powder container and the liquid injector

At the same time, the foils or membranes that hermetically seal the containers are perforated and can be easily removed after the mixing process has been completed. An injection nozzle can then be attached in its place for the simple and safe local application of the finished implant material.

Surprisingly, it has been shown that the device according to the invention is much easier and safer to handle than known mixing devices. It was also found that the invention, which is based on a simple modular system, is suitable for mixing vessels that may

0 are usually filled with different implant materials, optionally

and the respective concrete, practical clinical requirements

This possibility is very advantageous and offers the clinician completely new therapeutic possibilities.

Advantageous further developments of the device according to the invention are claimed in the subclaims.

The invention is explained in more detail in the following description of an embodiment in conjunction with the drawing, which shows:

&iacgr;&ogr; Fig. 1 is a partially along the longitudinal center plane

sectional and partially broken view of the preparation and application device according to the invention; and

Fig. 2 one in Fig. 1 within the dotted oval

2 lying detail in longitudinal section, which

the sealed guide of the mixing shaft in the container cap is illustrated.

The preparation and application device according to the invention, designated as a whole with 10, combines various construction units and

consists essentially of a vessel, the powder container A, for holding any implant material in the form of a powder or granulate, if necessary in combination with one or more pharmaceutical active ingredients, an integrated vacuum pump B _, a perforation cylinder C, a liquid injector D containing the mixing liquid and a guide cup E.

ToA :

The container 12 for holding the dry substance ("powder container") is made available to the user with the implant material filled in (dry components, preferably in the form of fine powders and/or granules) and the perforation cylinder 14 screwed in.

The powder container is closed at one end by a closure cap 16. The opposite opening is closed by a lamella 18 which is firmly integrated into the perforation cylinder 14. A piston 20 which can be moved in the axial direction in the powder container 12 is embedded in the closure cap, as well as a filter disk 22, a valve 24 and a pressure gauge 26 for measuring the negative pressure in the powder container during the mixing process.

The closure cap 16 has a central, axial opening through which a mixing shaft 28 with mixing paddle 30 and predetermined breaking point 32 is guided in a precise and sealing manner.

ToB:

The vacuum hand pump 34 is mounted on the mixing shaft 28 in an axial extension. This consists of the pump housing 36 and a housing front wall 38. A pump shaft 40 with handle 42 and pump piston 44 is guided through a central, axial opening in the housing front wall 38. A valve 46 is located in the bottom of the pump housing facing the container.

ToC:

The perforation cylinder 14 carries in its central, cylindrical opening a cylindrical disc-shaped body 48 which is displaceable in the axial direction and in which a 0 perforation cannula 50 tapered at both ends is centrally integrated, as well as a disc-shaped handle 52.

ToD:

The liquid injector 54 for receiving the liquid implant components is made available to the user with mixing liquid filled in. At one end it tapers to a cylindrical nozzle 56 which is closed by a film or membrane 58. The opposite opening is also closed by a film or membrane 60. In the liquid injector there is a piston 62 which can be moved in the axial direction and has sealing lips 64 and a central nozzle 66 which has a cylindrical opening 68.

ToE:

The cylindrical guide cup 70 serves to accommodate and guide the liquid injector. Three push rods 72 are embedded in the base of the guide cup, which are tapered at the free ends 74 and have a cross profile in cross section.

To use the device, the mixing shaft 28 with the mixing element designed as a mixing paddle 30 is first pushed completely into the powder container 12. The liquid injector 54 is pressed with its nozzle 56 into the cylindrical opening of the perforation cylinder 14 screwed into the container 12. In the process, the membrane 58 of the nozzle 56 is pierced by one end of the perforation cannula 50. At the same time, the nozzle 56 of the liquid injector 54 pushes the disk piston 48 of the perforation cylinder 14 in the direction of the powder container 12, with the other end of the perforation cannula 50 piercing the lamella 18 in the perforation cylinder. There is now a continuous connection between the powder container 12 and the liquid injector 54. The liquid injector is now pushed axially into the guide cup and pressed against the tips 74 of the push rods 72. These break through the film 60 of the liquid injector

0 54 and in turn push the piston 62 towards the powder container 12,

whereby the liquid from the liquid injector 54 through the perforation

cannula 50 of the perforation cylinder 14 is injected into the mixing chamber of the powder container 12.

Now the pump shaft 40 of the vacuum hand pump 34 is moved up and down using the handle 42. The work of the pump piston 44 removes the air from the powder container via the two valves 24, 46, which open and close depending on the path of the pump piston. The negative pressure generated in the powder container can be measured and monitored using the pressure gauge 26 during the entire mixing process.

As soon as the desired negative pressure is achieved in the system, the pump housing 36 with the pump shaft 40 fully inserted is used as a handle for operating the mixing shaft 28 with the mixing paddle 30. By rotating the mixing paddle 30 up and down, the dry and liquid components of the implantation material are mixed homogeneously in the powder container 12 for a predetermined time. As a result of the negative pressure in the system, air inclusions are removed from the implantation material.

After the mixing process has been completed, the mixing shaft 28 is completely removed.

0 until the mixing paddle hits the cap 16. Then

the mixing shaft above the closure cap broke off at the predetermined breaking point 32.

Now the liquid injector 54 together with the perforation cylinder is unscrewed from the powder container 12 using the handle 52. Instead of the parts removed in this way, a nozzle ("snorkel") can now be screwed into the opening of the powder container and this can be inserted into a conventional application gun. The implantation material can then be squeezed out of the powder container by pressing down the piston 20 using the application gun.

0 and apply via the nozzle directly into the bony implant bed.

Fig. 2 shows the sealing of the mixing shaft 28 in the closure cap 16 or the piston 20 provided in the closure cap. It can be seen that this sealing is achieved by two O-rings 76 which are spaced apart from one another in the longitudinal direction and are arranged between a sleeve 78 surrounding the mixing shaft 28. In the fully inserted position of the mixing paddle 30 in the container shown in Fig. 1, a through opening 80 in the mixing shaft 28 is opposite the sleeve 78, which in turn is provided with a through opening 82 which opens into a passage channel 84 which opens into the interior of the container and is provided with the self-closing valve 24. It is therefore clear that when the hand pump 34 is operated by pulling up the piston 44, the vacuum created under the piston takes effect via the hollow interior of the mixing shaft 28, the passage openings 80 and 82 and the passage channel 84 in the interior of the container and reduces the pressure prevailing there. The interaction of the valves 24 in the piston and 46 in the pump 34 ensures that any excess pressure that may arise in the housing 36 of the pump 34 during the downward stroke of the piston 44 closes the valve 24 and is vented to the atmosphere via the valve 46. The negative pressure created in the container 12 can then be further reduced by subsequently operating the hand pump 34.

Claims (9)

1. Preparation and application device ( 10 ) for implant materials to be prepared from at least one powdered or granulated component and one liquid component immediately before use, with a first container ( 12 ) which holds the powdered or granulated component in a sterile manner and a second container ( 54 ) which holds the liquid component in a sterile manner and which can be connected to the first container ( 12 ), wherein means are provided for establishing an overflow connection between the containers, for displacing the liquid component from the second container into the first container ( 12 ) and for intimately and homogeneously mixing the components in the first container by moving a mixing element ( 30 ) arranged in the first container and arranged on a mixing shaft ( 28 ) which leads out of the container in a sealed manner, and the first container is designed to be connectable to a vacuum source, characterized in that
that the mixing shaft ( 28 ) which is sealed out of the first container ( 12 ) is hollow and is connected at its outer end to a hand pump ( 34 ) for generating the negative pressure and is connected to the hand pump ( 34 ),
that the hollow mixing shaft ( 28 ) is provided with a through-opening in the region which is sealed through the container wall in the fully inserted position, which is connected to a passage channel which opens into the container wall in this region, is provided with a self-closing valve ( 24 ) and leads into the interior of the container,
that a measuring device ( 26 ) indicating the negative pressure prevailing in the container can be connected to the first container ( 12 ), and
that the housing ( 36 ) of the hand pump ( 34 ) is designed to act as a handle for moving the mixing shaft ( 28 ). 2. Device according to claim 1, characterized in that a perforation cylinder ( 14 ) is provided for connecting the first container ( 12 ) to the second container ( 54 ), which is tightly closed by a lamella ( 18 ) in its end region facing the first container ( 12 ) and can be inserted into a receptacle of the first container ( 12 ) and secured there, and into which a nozzle ( 56 ) protruding from the second container ( 54 ) and tightly closed by a membrane ( 58 ) can be inserted, that in the interior of the perforation cylinder ( 14 ) a disk-shaped body ( 48 ) is arranged displaceably in the longitudinal direction of the perforation cylinder ( 14 ), which is penetrated by a hollow perforation cannula ( 50) protruding on both sides and sharpened at both ends, and that the length of the perforation cylinder (14) protruding from the second container (12) is 100 mm long. 54 ) is dimensioned such that, when inserted into the perforation cylinder ( 14 ) fastened in the receptacle of the first container ( 12 ), the latter displaces the disk-shaped body ( 48 ) in the direction of the first container ( 12 ), wherein both the lamella ( 18 ) closing the perforation cylinder ( 14 ) and the membrane ( 38 ) closing the nozzle ( 56 ) of the second container ( 54 ) are pierced by the perforation cannula ( 50 ). 3. Device according to claim 2, characterized in that the second container ( 54 ) is tightly closed at its end opposite the nozzle ( 56 ) by a membrane ( 60 ), to which a displaceable piston ( 62 ) sealed to the inner wall of the container ( 54 ) is arranged in the interior of the container, and in that the second container ( 54 ) is displaceably held in a guide cup ( 70 ), from the closed bottom of which push rods ( 72 ) project at their free ends ( 74 ) which are tapered and which, when the guide cup ( 70 ) is displaced in the direction of the nozzle ( 56 ) of the second container ( 54 ), pierce the membrane ( 60 ) which tightly closes the bottom of the second container and displace the adjoining piston ( 62 ) in the direction of the nozzle ( 56 ). 4. Device according to one of claims 1 to 3, characterized in that the mixing shaft ( 28 ), which is guided in a sealed and displaceable manner by a closure cap closing the first container ( 12 ), is provided with a predetermined breaking point ( 36 ) which, in the position in which the mixing shaft ( 28 ) is completely pulled out of the first container, is arranged outside the container in the region of the closure cap ( 16 ). 5. Device according to claim 4, characterized in that the closure cap ( 16 ) is penetrated by a displaceable piston ( 20 ) which rests sealingly against the inner wall of the first container, the end face of which faces away from the interior of the container approximately flush with the closure cap ( 16 ) in the initial position, but is displaceable in the direction of the receptacle for the perforation cylinder ( 14 ) by exerting a force directed into the interior of the container. 6. Device according to one of claims 1 to 5, characterized in that the hand pump ( 34 ) arranged at the outer end of the mixing shaft ( 28 ) for generating the negative pressure in the first container ( 12 ) is designed as a piston pump with a piston ( 44 ) arranged in a cylindrical housing ( 36 ), which can be moved in the housing by a pump shaft ( 40 ) leading out of the housing end wall ( 38 ) facing away from the first container and having a handle ( 42 ) provided at its free end. 7. Device according to claim 6, characterized in that in the front wall of the pump housing ( 36 ) connected to the mixing shaft ( 28 ) there is provided a valve ( 46 ) which closes automatically when a negative pressure is generated on the container side in the hand pump by displacement of the pump piston ( 44 ) and opens when an excess pressure occurs. 8. Device according to one of claims 2 to 7, characterized in that the receptacle for the perforation cylinder ( 14 ) is provided with an internal thread and the perforation cylinder ( 14 ) is provided with a complementary external thread. 9. Device according to claim 8, characterized in that the perforation cylinder ( 14 ) is provided with a handle ( 52 ) of enlarged diameter.