Abstract:
In order to enable application of a dry i.e. powdery or granulated active substance, said substance is kept apart from a liquid supply in a dispenser. The powder is discharged with the help of said liquid during application. The liquid serves as a carrier for the active substance and is mixed with the liquid to varying degrees prior to discharge. The dispenser ( 11 ) has a liquid chamber ( 21 ) in an ampoule ( 19 ) which is provided with a closure stopper ( 26 ) which can be pierced. The liquid flow which is released upon actuation penetrates into a medium storage chamber ( 43 ), is mixed with the medium ( 51 ) therein and exits via an opened discharge outlet ( 44 ) in the form of a spray mist, jet or drop.

Description:
FIELD OF APPLICATION AND PRIOR ART 
     The invention relates to the application or discharge of media, particularly pharmaceutical products in atomized, jet or drop form and a dispenser for the same. 
     WO 96/24439 discloses a disposable dispenser, in which a glass ampoule sealed by a rubber plug and containing a liquid medium is inserted in a sleeve connected to a dispenser by means of a preset breaking connection. The dispenser has a projecting nose adapter with an atomizing nozzle at the end. A central shaft or member in the interior of said adapter carries in the centre a needle which, on actuation by a manual pressing of the sleeve into the adapter, perforates the rubber plug. The shaft then presses the rubber plug as a plunger into the ampoule and consequently produces the application pressure. 
     This disposable atomizer is very reliable and is eminently suitable for the application of liquid medicaments, particularly those which have to be rapidly absorbed by the body, e.g. by the nasal mucosa, whilst also avoiding incompatibilities for the digestive tract which can arise in the case of oral ingestion. However, there are medicaments, which are not stable for a long period in liquid form. 
     Although there are numerous proposals for powder application and dosing, this is problematical and only possible by whirling up in large air quantities. This eliminates many fields of application, because a planned application is scarcely possible in this way. 
     U.S. Pat. No. 3,756,390 relates to a hypodermic syringe, which has two chambers for liquid and powder separated from one another by a piercing foil. To the powder chamber is connected a connecting piece in which a needle can be inserted after removing a protective cap. After piercing the separating foil the two media are mixed together. The protective cap is then removed, the needle inserted and injection carried out following air ejection. A similar procedure occurs in U.S. Pat. No. 3,595,439 A for a mixing cartridge for dental two-component material. 
     GB 1 453 591 describes an ampoule, which has a perforatable sealing plug for a liquid chamber and an intermediate plug for a powder chamber. On needle perforation, e.g. connected to a drop, the intermediate plug is ejected, so that the two media can mix with one another. The mixture can then pass through an extra channel into the drop chamber. 
     JP 8-280907 A discloses an adapter, which has a liquid chamber sealed by an aluminum foil and which can be mounted on a container with a freeze-dried pharmaceutical. On the other side of the adapter sealed with a screw cap can be engaged a pump atomizer, which with its suction tube perforates the aluminum foil and thus interconnects the liquid chamber and powder container. This dispenser which has to be assembled from three separate parts prior to use is not very helpful for uncomplicated use purposes. 
     PROBLEM AND SOLUTION 
     The problem of the invention is to provide a method and a dispenser for the application of two different media with which solid media can also be applied reliably, as well as in dosed, planned manner. 
     The invention provides a method in which a liquid is used as the carrier medium for the particulate solid medium and the separately stored media are only mixed together prior to their application. The term particulate solid medium is understood to mean that it is not in the form of a gas, liquid, paste or massive form, but instead normally dry with a certain flowability or free-flow capability and is in particular pulverulent or granular. Thus, it is possible to store the two media separately from one another and the active substance can be present in dry form usually in the particulate medium. It can e.g. be a pharmaceutical product in the form of a freeze-dried powder. Only just prior to application is it mixed with a liquid serving as the carrier medium. Either a suspension (dispersion) or also a solution can be obtained, which are then jointly applied, preferably as a spray mist, but also in drop or jet form. 
     Apart from the advantage that the product can be kept better in the dry powder form, the advantage also arises that the liquid can be so chosen that the absorption by the mucosa is particularly aided. There is no need for preservatives. 
     The particulate solid medium should preferably be pulverulent, but at least flowable or free-flowing and readily mixable with the liquid, so that in the relatively short available an intimate mixing or dissolving in the liquid is possible. However, it is also possible for the particles to be present in the form of so-called microcapsules, i.e. comprising the contents covered by a skin. 
     The direct and very immediate application following mixing is possible if the liquid is introduced into the solid medium under an application pressure and the resulting mixture is discharged under said application pressure. However, it is also possible to carry out mixing in a mixing phase directly upstream of the discharge or application. This e.g. makes it possible to ensure that firstly all the liquid is introduced into the chamber containing the solid medium prior to the start of application. In the case of particularly solution-active mixtures this can ensure a dissolving, or at least a good suspension of the solid medium in the liquid. The liquid acts as a carrier for the solid, but can itself have or contribute to pharmaceutical actions. 
     Advantageously between the mixing phase and the application phase there is a pressure point which has to be manually overcome for the actuating force, so that automatically there is a certain intermediate stop. The solid medium will not usually completely fill the chamber in which it is stored, which will contain an in part relatively large volume fraction of gas, e.g. air or also an inert gas aiding product stabilization. On mixing said gas can be compressed on introducing the liquid, so that finally on application, i.e. the opening of the solid reservoir or a mixing chamber there is already a certain initial pressure, which e.g. ensures a good atomization from the outset. 
     In addition, a dispenser is proposed, which has a liquid chamber, pressurizing means for producing an application pressure and for delivering liquid into a medium reservoir, separate from the liquid chamber, for a pulverulent or free-flowing solid medium and a discharge orifice for the mixture. The pressurizing means can be a thrust piston pump, whose cylinder can be the liquid chamber. 
     Prior to the actuation of the dispenser it is possible to keep the liquid chamber and the medium reservoir tightly sealed with respect to one another and the outside and only to connect the same with one another and to the discharge orifice through actuation. This can take place by perforating membrane-like pistons or container walls, by lip valves or the like. 
     The building up of pressure points, which permit the build-up of certain minimum actuating forces can take place both prior to the start of actuation and also between the mixing and application phase, e.g. by snap connections, but preferably by preset breaking points, i.e. material bridges which can be destroyed by actuating forces. 
     In the case of dispensers, which have a separate container for each application charge discharged all at once or in a few successive actuations, the opening of a medium chamber usually takes place by a thin, hollow needle, e.g. a steel needle, which is sharpened by a bevel and usually has a very small diameter below 1 mm. It is received in a shaft, which usually also presses the perforatable piston into the cylinder. In order to receive this thin, sensitive needle, it has hitherto been provided with a metal adapter, which was externally fitted to the needle as a relatively thick, solid, metal ring. It permitted an engagement of an assembly tool and was pressed into the shaft by means of an annular locking tooth system (cf. WO 96/24439). This arrangement has proved satisfactory and was considered unavoidable due to the reliable assembly without damaging the sensitive tip. However, it requires the metal adapter as a separate part, which increases costs and also the metal fraction in the dispenser which can otherwise be disposed of virtually in type-pure manner. 
     It has now been found that it is possible to fit the very thin and sensitive needle in damage-free manner with the necessary sealing action without said adapter. For this purpose it is introduced between the entire central area between the ribs of a larger bore in the shaft embracing both ends of the needle and at the end is pressed with press fit into a bore, which is somewhat longer than the needle diameter. It is supported on a shoulder within said bore and can consequently freely communicate to the discharge orifice. On insertion the needle is held at its end carrying the tip by a collet, which has a central pin engaging in the needle and consequently preventing a crushing and damage to the sensitive tip. This is important, because damage-free tips are necessary for the perforation of the closing plug in the same way as in a hypodermic needle, so as to avoid the needle detaching particles from the container or piston wall on penetrating the same and which would lead to a clogging of the discharge orifice or could even enter the respiratory tracts of the patient. 
     These and further features can be gathered from the claims, description and drawings and the individual features, both singly or in the form of sub-combinations, can be implemented in an embodiment of the invention and in other fields and can represent advantageous, independently protectable constructions for which protection is hereby claimed. The subdivision of the application into individual sections and the subtitles in no way restrict the general validity of the statements made thereunder. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     An embodiment of the invention is described in greater detail hereinafter relative to the drawings, wherein show: 
     FIGS. 1 &amp; 2 Longitudinal sections through a dispenser in two operating positions. 
     FIGS. 3 &amp; 4 Longitudinal sections through other embodiments. 
     FIGS. 5 to  7  Three operating positions of a further, preferred embodiment, in each case in longitudinal section. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The dispenser  11  shown in FIGS. 1 and 2 is a disposable atomizer applying or discharging its complete charge in a single stroke. It has a casing  12  with an elongated adapter section  13 . It projects centrally out of a casing actuating shoulder  14 , which is oval in plan view and projects to two sides in epaulette-like manner. A casing jacket  15  directed in opposition to the adapter is connected to the shoulder  14  and has on its flatter sides in each case an actuating cutout  16 . 
     Through the actuating cutout  16  the actuating face  17  of a sleeve  18  is accessible with a finger, which receives a glass ampoule  19 , supported in the sleeve by webs  20  and which contains a liquid chamber  21 . The sleeve  18  and ampoule  19  are in the form of elongated, deep, circular cylindrical containers. 
     Onto the plastic sleeve is shaped a ring  23  by means of thin, preset breaking point-forming, web-like material bridges  22  and which is received in a snap connection  24  on the underside of the shoulder, adjacent to the inner area  25  of the substantially hollow adapter  13 . 
     The liquid chamber  1  in the ampoule  19  is sealed by a plug  26  made from a rubbery material and which sealingly engages on the circular cylindrical wall of the liquid chamber  21 . It is relatively elongated and has central recesses  28 , emanating from each of its end sides and which are separated by a central web  29 , which forms a perforatable membrane. The sleeve  18  and ampoule  19  project centrally into the inner area of the adapter  13  and are guided there with the outer wall of the sleeve  18  and an upper flange  30  of the ampoule  19  on lateral webs  31  in the interior  25  of the adapter  13 , namely over the length of an actuating path. 
     At the end of the actuating path a plunger  34  is received by means of a ring  32 , which is connected thereto by means of preset breaking point-forming material bridges  33  and which extends in the interior of the adapter  13  centrally up to just before the ampoule  19  or its plug  26 . In the interior of the plunger  34  there is a connecting channel  35 , which is connected to the inner channel  36  of a hollow ram  37 , which comprises a steel needle on which, directed towards the plug, is formed by bevelling a tip  38 . The steel needle is received in a relatively solid metal adapter ring  39 , which is externally provided with an annular, barb-like tooth system. By means of the latter it is pressed into an opening  40  in the plunger  34  connected to the connecting channel. 
     The connecting shaft  34  is guided and sealed above its predetermined breaking ring  32  by sealing and guiding lips  41  located in the interior  25  of the adapter  13 . By a sealingly mounted end cap  42  forming the end of the adapter  13  an annular space is formed around the shaft  34  forming a medium reservoir  43  for a solid medium, e.g. a powder. Centrally in the end cap  42  is provided a discharge orifice  44 , which is constructed as a spraying nozzle. It produces a conical spray jet with the aid of a vortex channel construction  45  at the front end of the shaft  34  and in operation it engages on the inside of the discharge nozzle  44 . Spirally constructed channels ensure an angular momentum of the liquid or mixture rapidly flowing through them. 
     Between the nozzle interior and the end face of the shaft  34  is formed a discharge chamber  46 , which is sealed with respect to the medium reservoir  43  by sealing lips  47  of the end cap  42 . Adjacent to the sealing lips the discharge chamber contains in its cylindrical wall overflow channels  48 . 
     The connecting channel  35  in the shaft  34  ends in lateral openings  49 , formed by a transverse channel, on the shaft surface. 
     All parts of the dispenser with the exception of the glass ampoule  19  and the ram  37  formed by a steel needle with a metal adapter ring, are made from plastics. The liquid chamber  21  is filled with a liquid intended to mix on flowing out with a particulate solid medium in the medium reservoir  43 , so as to dissolve or suspend respectively disperse the same and discharge it together with the liquid. The solid medium is a pharmaceutically active substance, usually in powder form. The liquid mainly preponderantly comprises water, which is present in a sterile form and optionally in a form physiologically adapted to the body fluid. However, also other liquids or liquid additives are possible, which can have characteristics furthering or initiating the activity of the solid medium. A two-component action can arise between the liquid and the solid medium. 
     The dispenser according to FIGS. 1 and 2 is in the position shown in FIG. 1 in the packing, storing and sale state. The liquid chamber  21  is filled with the liquid  50  and tightly sealed by the plug  26 . The ram  37  is just above the web  29 . The solid medium  51  is located in the medium reservoir  43 , but there can simultaneously be present a normally even large quantity of air, which is due to the gaps between the particles, but which can also be additionally present so that the particles do not have to be filled in an excessively compacted form. The medium reservoir  43  is tightly sealed to the outside and inside by sealing lips  41  and  47  and the corresponding cylinder surfaces of the shaft  34 . 
     For using the dispenser  11  the elongated adapter  13  is brought into the corresponding dispensing position, e.g. inserted in a nostril. The user grips the dispenser by placing two fingers on the shoulder  14 , whilst pressing on the actuating face  17  with the thumb. He must initially exert a relatively high actuating pressure in order to destroy the preset breaking points formed by the material bridges  22  between the ring  23  and the sleeve  18  and which also form a tamper-evident closure. 
     The unit formed by the sleeve  18  and ampoule  19  is then moved upwards, i.e. into the interior  25  of the adapter  13 . The needle-like ram  37  perforates the web  29  in the closing plug  26  and the lower face  52  of the shaft  34 , which has a somewhat smaller diameter than the liquid chamber  21 , strikes the face  53  of the plug  26 . The latter consequently forms the piston of a thrust piston pump, whose cylinder is formed by the liquid chamber  21  or glass ampoule  19 . 
     The upwardly directed axial pressure acting on the shaft  34 , on actuation, also breaks the material bridges  33  connecting the ring  32  to the shaft  34 , so that the shaft  34  is moved upwards in FIG. 2 until its upper face engages with the vortex channel construction  45  on the upper end wall bounding the discharge chamber. As can be seen in FIG. 2, in this position the connecting channel  35  is connected by means of the lateral openings  49  to the annular medium reservoir  43 , but which remains sealed by the lips  41  to the adapter interior  25 . However, the upper sealing lip  47  is bypassed by an annular groove  54  in the shaft, so that a discharge flow channel is formed via the overflow channels  48  and the vortex channel construction  45  to the discharge orifice (nozzle)  44 . 
     The pressure of the shaft  34  on the plug/piston  26  produces the necessary application pressure, which delivers the liquid through the needle  37 , the connecting channel  35  and the openings  49  into the medium reservoir  53 , where it is mixed with the solid medium  51 , which can be aided by the design of the medium reservoir and/or the openings  49 , e.g. through their inclined position for the production of a vortex. The resulting mixture is then discharged from the discharge orifice, particularly in finely sprayed form. The sealing lips  47  together with the upper piston section  47   a  or the groove  54  form the discharge valve. The dispenser is intended with a single, but in this case two-stage actuating stroke to discharge the complete solid medium and liquid charge stored in it in separate and tightly sealed form. 
     Apart from the differences described hereinafter, the construction of the dispenser according to FIG. 3 is the same as that shown in FIGS. 1 and 2. Reference is made to the description of the latter and the same reference numerals are used. 
     In the sleeve  18  is received an ampoule  19 , which is longer than that according to FIG.  1 . In axially succession it contains both the liquid chamber  21  and also the medium reservoir  43   a . Thus, apart from the closing plunger  26  sealing the medium reservoir  43   a  here, the ampoule  19  contains an intermediate piston  55  separating the liquid chamber  21  from the medium reservoir  43   a  and which in the rest state shown in FIG. 3 seals the two chambers from one another. For the connection thereof a connecting channel  35   a  is formed in the wall of the ampoule  19  and its outlet into the medium reservoir  43   a  is sealed in the rest state of the intermediate piston  55 . 
     The shaft  34  is sealingly inserted in a support section  56  of the adapter  13 , which is constructed in one piece with the casing  12  (and therefore with the adapter  13 ). The hemispherical adapter end  57  is also constructed in one piece therewith in that also the nozzle-like discharge orifice  44  is provided. On its upper end face the shaft contains the vortex chamber construction  45  cooperating with the discharge nozzle. The shaft receives the ram  37 , which is formed by a steel needle and extends almost entirely through the shaft  34  up to just before its upper face. The needle, which generally has an external diameter of less than 1 millimetre and a correspondingly small wall thickness, is very carefully sharpened for forming a sharp, burr-free tip  38  and without the adapter  39  shown in FIG. 1 is directly inserted in a bore  58  of the shaft. This bore has a much larger diameter than the needle  37 , but guides the latter through e.g. four webs  59  projecting radially inwards from the bore inner wall and which commence with an insertion bevel  60  in the vicinity of the face  52  of the shaft  34 . They ensure a precise centring and prevent buckling of the thin needle on insertion. They extend from the free end of the shaft up to a fitting bore  61 , i.e. over most of the central area of the needle particularly important for preventing buckling. 
     At the upper end, i.e. that remote from the tip  28 , the needle  37  is pressed into a fitting bore  61 , which is so dimensioned that it permits a tight press fit of the needle therein. A shoulder  62  in said fitting bore forms an upper stop for the pressing in of the needle. The fitting bore embraces the upper end of the needle over a length greater than a multiple, e.g. five times the external diameter of the needle. The upper end of the fitting bore is connected to the discharge chamber  46 . 
     The dispenser comprises very few parts. The shaft  34  with the needle fitted therein is inserted in the one-piece casing, in which is directly shaped the discharge orifice  44 . The dispenser is completed by the sleeve  18 /ampoule  19  unit with closing plug  26  and the intermediate piston  55 , separating the liquid and the medium chamber. 
     The assembly of the dispenser in accordance with FIG. 3 is very simple. As a result of the novel construction of the shaft  34  the needle can be fitted without the annular adapter  39  in accordance with FIG.  1 . The ribs  59  guide the needle on entering the bore  58 , without opposing an excessive resistance in the longitudinal direction. Only when the needle has been guided over most of its length between the ribs does it enter the fitting bore  61 , where it is pressed in in a sealing manner so as to be secured mechanically against extraction. As can be gathered from the drawing, only over a relatively small part of its length, usually less than one third, does the needle project from the shaft  34 . Thus, the section most endangered by buckling, which is in the centre of the needle, when force is applied for its pressing into the fitting bore  61 , is already guided in buckling preventing manner between the ribs. 
     It is particularly important that the sensitive needle tip  28  is not damaged during the pressing in process. Therefore working takes place with a tool, which grips the needle from the outside with a type of collet (in the area projecting from the shaft), but which additionally has a central pin engaging in the needle bore and consequently protecting the needle against crushing and damage to the tip. 
     The prefitted shaft can then be pressed into the connecting piece  56  with its upper, partly bevelled offset end. 
     The prefitted unit constituted by the sleeve and inserted ampoule  19  is fitted by means of the snap closure  24  to the casing  12 . Beforehand the ampoule was filled with the liquid, followed by the fitting of the intermediate piston  55  and then the filling of the solid medium into the medium reservoir  43  above it. The closing plug  26  was then fitted. 
     As in FIGS. 1 and 2, on actuation the preset breaking point  22  is destroyed for obtaining an adequate initial pressure, which ensures that the user continues to the end the actuation with a certain force and speed. An interim interruption would e.g. lead to the dripping of the atomizer and would optionally impair the mixing of the substances or prevent a complete application. 
     Then the ram  37  (needle) perforates the web  29  in the piston  26  and then opens the discharge channel  36 , mainly formed by t he interior of the hollow needle  371  with respect to the medium reservoir  43   a . The shaft  34  presses the piston  26  downwards and compresses the solid medium  51  in the medium reservoir  43   a , together with the air (or a corresponding inert gas) contained therein. Thus, the intermediate piston  55  is also pushed downwards and frees the connecting channel  35   a  in the ampoule wall. The latter could also be formed by a corresponding protuberance of said wall, which would then free an overflow channel on its two sides. The liquid  50  flows out of the liquid chamber  21  into the medium reservoir  43   a , where it mixes with the medium  51  and is passed with the corresponding discharge pressure via the needle bore  36  to the discharge orifice  44 . The sleeve  18 /ampoule  19  unit, guided by the webs  31 , slides upwards in the interior  25  of the nose adapter  13 . Here again a complete discharge of the two media (plus the third medium “air”) is possible. The air also forms a precompression, which aids the start of the atomizing phase. Optionally the arrangement could also be such that the medium was placed in the bottom-near area of the ampoule and the liquid above it. In this case the liquid would firstly flow downwards, mix there with the medium and then flow through the liquid chamber to the outlet. This could optionally bring about a particularly intimate mixing. 
     FIG. 4 shows a particularly simply constructed embodiment. In an ampoule  19 , which can also be made from plastic and is in the form of a particularly deep bowl, is guided a liquid piston  64  sealing with piston lips and which is constructed in one piece at the lower end of a piston rod  65 . A connecting chamber  63  receives the ball on being pressed out and a vortex channel/nozzle arrangement  80  similar to the nozzle  44  with vortex channel  45  ensures a jet distribution aiding the mixing of the media, optionally accompanied by angular momentum and atomization in the medium reservoir  43   b.    
     It has a through central bore  66 , in whose upper section is pressed a ball  67  as the sealing valve. Over the end of the piston rod  65  is engaged a sleeve-like adapter cap  13   b , so that between the upper face  68  of the piston rod  65  and the interior  69  of the adapter cap  13   b  is formed the medium reservoir  43   c . A discharge orifice  44  formed at the end of the adapter cap can be constructed as a spray or drop nozzle. It is sealed by a pull-off closure  70 , e.g. a sealed-on aluminium foil. 
     The adapter cap  13   b  has lateral actuating shoulders  14   b  and engages with its lower part in the interior of the ampoule  19 , i.e. it is guided on the cylinder wall  27 . Resilient tabs  71  disengaged from the wall of the adapter cap  13   b  form together with a groove in the cylinder wall  27  on the one hand a snap closure securing the rest state and preventing a pulling of the adapter cap  13   c  from the ampoule and on the other ensure the necessary actuating force build-up prior to the start of actuation. As a result of the barb-like construction pulling off can be prevented and the actuating force build-up can be dimensioned in a predetermined manner. 
     This dispenser comprises a few relatively simple plastic parts, a foil portion and a small steel or plastic ball. It could also be replaced by a perforatable membrane or a membrane tearing through liquid pressure. 
     On production the liquid chamber  21  is filled with liquid  50 , the piston/piston rod unit  64 ,  65  is inserted and then the adapter cap  13   b , filled with the medium  51 , is inserted. 
     For using the dispenser according to FIG. 4 firstly the pull-off closure  70  is pulled off, so that the discharge orifice  44  is open. Then, accompanied by the overcoming of the pressure point produced by the spring tabs  71 , the piston  64  is pressed into the sleeve  19  (or vice versa). The resulting liquid pressure forces the ball  67  out of the overflow channel  66  into the chamber  63 . The liquid sprays with an angular momentum in a sharp jet or atomizes in the medium reservoir  43   b , mixes there with the medium  51  and passes as a mixture out of the discharge orifice  44 . 
     Here again, prior to actuation, the individual chambers must be completely sealed with respect to one another and to the outside. The pull-off closure  70  could also be replaced by a valve opening in pressure-dependent manner, but is generally unnecessary in the case of a disposal dispenser. In this or the following construction according to FIGS. 5 to  7  it is also possible to use a discharge valve, which is deliberately opened by the user only following a mixing phase, e.g. a rotary slide valve, which is operated by rotating the upper section of the adapter cap  13 ,  13   b  with respect to the remaining casing. As a result of the rotation it would also be possible to free a stop, which prevented the piston rod during the first actuating step (mixing) from immediately discharging the mixture. The time required for operating the rotary valve could e.g. ensure the dissolving of the powder in the liquid. 
     In connection with the embodiments according to FIGS. 5 to  7  reference is again made to the detailed description of FIGS. 1 to  3  and only differences are described hereinafter. 
     The main difference is the unit containing the media and comprising the sleeve  18  and the ampoule  19 . The sleeve  18 , which is fitted to the casing  12  by means of the preset breaking ring  32 , contains the liquid chamber  21  in its lower area facing its bottom  17 , where a plastic ram  37   c  is formed, which projects centrally upwards in the sleeve and has a cruciform cross-section. 
     In piston-like sealing manner an inner sleeve  19   c  is inserted in the sleeve and has on its bottom a perforatable membrane  29   c . This sleeve seals in the upward direction the liquid chamber. It is inserted by means of a preset breaking ring  32  into the interior  25  of the nose adapter  13 . The preset breaking ring operates with material bridges  33 , as described hereinbefore. The inner sleeve  19   c  forms a cylinder for a reservoir/mixing chamber  43   c , which is upwardly sealed by an inverted, sleeve-shaped closing plug  26   c  serving as a piston. 
     During the manufacture of the dispenser  11  according to FIGS. 5 to  7  the liquid  50  is introduced into the liquid chamber  21  and the solid medium  50  into the medium reservoir  43   c , which is sealed by the closing plug  26   c . The inner sleeve  19   c  is inserted in the manner of a piston into the sleeve  18 , which consequently forms the cylinder of a second thrust piston pump on said dispenser and upwardly seals the liquid chamber  21 . 
     On actuation firstly the preset breaking closure  32  is broken through. The ram  37   c  then penetrates through the membrane  29   d  and by means of the channels formed in the cruciform cross-section forms the connection between the liquid chamber  21  and the medium reservoir  43   d . The piston-like, lower part of the inner sleeve  19   c  reducing the size of the liquid chamber  21  feeds the liquid  50  into the medium storage space  43   c , which thereby increases in size, in that under the thus formed medium pressure it forces upwards the plug  26   c.    
     FIG. 6 shows the end of this mixing phase in which the liquid and solid medium are mixed. It is ended in that, as shown in FIG. 6, the bottom of the inner sleeve  19   c  engages on the bottom  17  of the sleeve  18 . There is then only a common mixing chamber  43   c . The air previously present in the medium chamber  43   c  can compress to a greater or lesser extent as a function of the resistance of the plug  26   c  and consequently maintain a basic pressure in the mixing chamber. 
     The preset breaking closure  32  can be set in such a way that the user, on reaching the position shown in FIG. 6, must apply a further, increased pressure, which ensures that there is an adequate time in the mixing chamber  43   c  for mixing and optionally dissolving the constituents. 
     As shown in FIG. 7, the preset breaking closure  32  then breaks, the needle  37  penetrates through the bottom  29   d  of the closing plug  26   c , which is then contacted by the face  52  of the shaft  34  and is pressed in the manner of a piston into the inner sleeve  19   c  forming a pump cylinder. The mixture  50 / 51  is then transported from the mixing chamber  43   d  via the discharge channel formed by the needle bore  36  to the discharge orifice  44  and is atomized there under the discharge pressure or is discharged in some other way. As described relative to FIG. 3, the application phase could be time-limited in addition to or in place of the preset breaking ring  32  by a stop released by rotation. It is also possible to use in place of the perforating needle a rotary slide valve which is opened by this rotation. 
     Thus, in this embodiment the mixing phase can be spatially and also time separated from the application phase, although everything substantially directly successively takes place, i.e. there is no risk of the solid medium being damaged in the mixing phase. It is also possible to distribute these two phases over two different actuating strokes instead of carrying them out in two axially succeeding stroke sections, as in FIGS. 5 to  7 . By a corresponding subdivision or sequence of strokes, it is also possible to discharge a charge premixed in a first stroke in two succeeding partial discharge strokes, in order e.g. to successively apply a medicament to the two nostrils of a patient. A multiple use dispenser or rechargeable dispenser in accordance with the above-described principle is also possible.