INJECTABLE STERILE MEDICINES OR SIMILAR SUBSTANCES,

SUITABLE FOR USE IN HIGH-SPEED LINES OF PRODUCTION OF

THE BOTTLES, RESPECTIVE SEALING CAP AND CORRESPONDING SEALED BOTTLE

Field of the invention

The present invention relates in general to the sector of bottles containing medicines or similar substances and of their packaging, and more particularly it relates to a device or assembly for the sealing of bottles or similar containers containing sterile or non-sterile medicines, of the injectable or non- injectable type, suitable for being used in lines of production and packaging of the bottles characterised by high speed and production capacity.

The present invention relates also to a new sealing cap suitable for being advantageously used in lines for the automatic packaging of sealed bottles containing injectable sterile medicines, a new process for the production of sealed bottles containing an injectable sterile medicine, and also an innovative line for the production and the packaging at high speed of sealed bottles containing an injectable sterile medicine.

Background of the invention and state of the prior art

Numerous systems, devices and processes are known in the art for sealing bottles containing medicines or powders or liquids, sterile, injectable, or similar substances, prepared in various ways.

In particular, in the case wherein the medicine contained in the bottle is a lyophilised medicine, the sealed bottles are produced in appropriate packaging lines, filling beforehand each bottle to be sealed with a pharmacological solution in a filling station.

The bottles are then introduced inside a machine for the lyophilisation which determines the sublimation of the liquid phase of the solution, after which the bottles are closed with a cap in rubber, and finally sealed by means of a nut in aluminium.

These sealed and packaged bottles, containing the lyophilised medicine, are used by removing from the respective sealing system a protection cap, for example of the flip-off type, so as to uncover an area of the rubber cap intended to be perforated by means of the needle of a syringe.

The user then injects in the bottle, by means of the syringe, a liquid, which is mixed with the lyophilised medicine contained in the bottle, so as to prepare a pharmacological solution intended to be injected.

Various systems and devices for closing and sealing bottles containing sterile medicines, injectable or non-injectable, are currently available and applied industrially, more or less on a large scale, and for example mention is made from among these known systems of the system known by the commercial code LYOSEAL.

These systems of sealing, currently available on the market, are not however free from some problems and disadvantages, which it would therefore be appropriate and desirable to remedy, and which in fact constitute the starting point of the present invention.

In particular, in relation to these products, although widely used, the following problems have been observed by the Applicant, which occur above all in the phase of assembly, packaging and sealing of these known bottles for injectable sterile medicines.

For example, a first problem of the LYOSEAL sealing system derives form the fact that it provides a first phase of production, wherein a rubber cap is rested on the bottle, and a subsequent phase, wherein a sealing assembly, in turn composed of an intermediate ring and a locking nut, is placed on the cap itself. In fact this mounting in separate and successive phases of the rubber cap and of the sealing assembly entails a lengthening of the times of production of the bottles.

A second problem of the LYOSEAL sealing system for bottles derives from the fact that the rubber cap and the sealing assembly formed by the intermediate ring and by the locking nut are not held together in a stable and secure manner, while the sealing assembly, pre-assembled, is handled in the line of packaging and sealing of the bottles, so that this sealing assembly is tendentially unstable.

As a result the pre-assembled assembly, at least in certain critical conditions, can be divided into its component parts, and for example the locking nut and the intermediate ring can be detached from the rubber cap, so as to determine anomalies and temporary interruptions in the line of packaging of the bottles, and therefore have a negative effect on the efficiency and productivity of this packaging line.

Another possible and potential problem of the LYOSEAL sealing system, again observed by the Applicant, depends on the material whereof the upper cover is constituted, or the external locking nut which receives the external pressure aimed at pressing and inserting completely the rubber cap in the mouth of the bottle in order to seal it.

In fact this locking nut is usually made of plastic material, and therefore tends easily to deform, with the risk of a consequent reduction in time of its capacity for fixing and locking stably the other two parts of the sealing assembly, i.e. the intermediate ring and the rubber cap, after the bottle has been sealed.

Yet another possible problem can be seen in the fact that the intermediate ring, of the sealing assembly of the LYOSEAL system, has in the undeformed configuration, at the tip area of the respective flexible tongues, an external overall dimension, i.e. an external diameter which is greater than that of the diameter of the bottle to be sealed.

For example, in the case of the standard named 2 , i.e. with bottles with external diameter of 16 mm, the intermediate ring has, at the tip of the respective tongues when they are still in the initial inclined configuration before being closed in the undercut seat formed around the mouth of the bottle, an external diameter of 16.8 mm, therefore greater than the diameter of the bottle.

In fact these sealing assemblies which, as mentioned previously, are pre-assembled and rested each one on the rubber cap, in turn already partially inserted in the mouth of the bottle, along the relative line of packaging, before being definitively pressed onto the bottle, containing the lyophilised medicine, or more generally a medicine or a powder prepared in whatsoever manner, so as to seal the bottle, tend inevitably to come into contact and to hit one against the other with the tongues of the respective intermediate rings, while the bottles are handled in contact one with the other and conveyed along the production line, precisely due to the greater diameter which these tongues have as a whole in the tip area in relation to that of the bottles to be sealed.

As a result, due to these contacts and impacts, the sealing assemblies can be inclined or fall and therefore take on an incorrect position, in particular while they are moved along the modern lines of automatic packaging at high speed of the bottles, automatic lines which can even handle 16,000 bottles in an hour, so as to create problems, possible anomalies and interruptions during the handling of the bottles, and therefore negatively influence the productivity of these packaging lines.

Again, irrespective of the specific problems, such as those observed by the Applicant and mentioned previously and which should be appropriately remedied, in the LYOSEAL system and in other products or systems of sealing currently available on the market, it has to be considered how this sector of packaging and sealing of bottles containing injectable sterile medicines is extremely delicate and sensitive to receiving ever new innovations and improvements, aimed both at increasing the efficiency of the lines of packaging of these sealed bottles for injectable sterile medicines and also at guaranteeing greater safety and quality of the end product, i.e. of the sealed bottle containing the injectable sterile medicine.

Summary of the invention

Therefore a first object of the present invention is to provide an assembly for the sealing of bottles containing sterile or non-sterile injectable medicines, for example but not exclusively lyophilised medicines, therefore also powders, liquids, and/or substances and/or medicines prepared in whatsoever way, which is suitable for being assembled and applied rapidly, safely and reliably, and with a limited number of operations, in the lines of packaging and sealing of these bottles, so as to increase considerably the efficiency and the productivity of these lines of packaging and therefore also reduce substantially the costs of production and packaging of the sealed bottles.

A second object of the present invention, more particular but still connected to the first, is that of introducing specific improvements and perfectionings which allow the various problems to be eliminated completely, as observed by the Applicant and mentioned previously, which are present in the systems, known and currently in use, for the sealing of bottles containing injectable sterile medicines, and in particular those which are found in the phase of packaging of these sealed bottles, so as to make an effective leap towards a greater safety, efficiency and quality in the packaging and production of these bottles for injectable sterile liquids.

Another object of the present invention is that of going further and overcoming the typical limits of application of the known sealing systems for bottles, and therefore developing a very versatile sealing assembly which can be advantageously used for sealing bottles containing a wide range of medicines and preparations, either in solid form or in powder or in liquid form.

A further object is also that of proposing a new sealing cap which is suitable for being used with tangible benefits in the automatic lines of packaging and production of sealed bottles for injectable sterile fluids, and in particular allows the avoiding of problems, interruptions and other possible disadvantages, related to the use and to the handling of the sealing cap, which may negatively influence the efficiency and the function of these automatic lines of packaging and production.

Yet another object of the present invention is to propose a process, for the production of sealed bottles containing an injectable sterile medicine, which innovates and is characterised by a greater efficiency compared to known processes, and also propose an automatic line for the packaging and the production of these sealed bottles which implements this innovative process.

The aforementioned objects can be considered achieved in full by the sealing assembly for bottles containing injectable sterile medicines or similar substances, having the features defined by the independent claim 1 , by a respective sealing cap having the features defined by the independent claim 10, by a corresponding sealed bottle having the features defined by the dependent claim 12, and finally by a process for the production of sealed bottles and by a sealing and production line which implements this process having respectively the features defined by claims 13 and 15.

Particular embodiments of the present invention are moreover defined by the other dependent claims.

Advantages of the new sealing assembly and of the bottle sealed by means of this sealing assembly

The advantages, in part already implicitly disclosed before, which are associated with the new sealing assembly for bottles containing injectable sterile medicines or similar substances, proposed by the present invention, and which distinguish it in respect of the systems and the solutions currently in use, are multiple and important and listed herein below purely by way of an example.

Greater efficiency and productivity of the automatic line of production of the bottles, with considerable reduction of the times for sealing them.

- Great versatility, i.e. the possibility of using the sealing assembly in lines for the production and the packaging of sealed bottles containing a wide variety of medicines, lyophilised or otherwise, in liquid form or in powder, prepared in various ways.

Greater precision and efficiency in the phase of application of the elements of the sealing assembly, given that the sealing assembly is applied, already pre-assembled in its various elements and in a single operation, on the bottle to be sealed.

High stability in time of the sealing of the bottle, thanks to the use of metallic materials, such as aluminium, for making the parts of the system of sealing, which are able to tolerate without problems the rapid swing or thermal shock whereto the bottle is subjected during the process of lyophilisation.

Greater ruggedness of the system of sealing of the bottle. Reduced dimensions of the sealing system in respect of those known and already in use on the market.

- Applicability for sealing bottles of different dimensions and features, conforming to the standards in commerce.

Brief description of the drawings

These and other objects, features and advantages of the present invention will be made clearer and more evident by the following description of one of its preferred embodiments, given by way of a non-limiting example with reference to the accompanying drawings, in which:

Fig. 1 is a photographic schematic view of a sealing assembly, according to the present invention, for bottles containing injectable sterile medicines or similar substances, broken down into the various parts whereof it is constituted;

Fig. 2 is a photographic view of a bottle for injectable sterile medicines, packaged and sealed by means of the sealing assembly of Fig. 1 ;

Fig. 3A is a normal view from below, on an enlarged scale, of a new sealing cap included in the sealing system of the invention of Fig. 1 ;

Fig. 3B is a view sectioned along line IIIB-IIIB of Fig. 3A;

Fig. 3C is a view from above of the sealing cap of Fig. 3A;

Fig. 4 is a schematic view, partially sectioned, of an intermediate retaining cage included in the sealing assembly of Fig. 1 ;

Fig. 4A is a view on an enlarged scale of some details, indicated by a dotted and dashed circle, of the retaining cage of Fig. 4;

Fig. 5 is a schematic sectioned view of a locking nut included in the sealing assembly of Fig. 1 ;

Fig. 6 represents in schematic form the various phases for mass packaging, in an automatic packaging line, of a bottle, containing an injectable sterile medicine, sealed with the sealing assembly of the invention;

Fig. 7 is a sectioned schematic view which shows the sealing assembly of the invention in a pre-assembled configuration, in which the sealing assembly is preliminarily set up and mounted on the respective bottle, before being pressed on the latter to seal it definitively;

Fig. 8 is a schematic sectioned view which shows the sealing assembly of Fig. 7 in an intermediate position during the application on the respective bottle;

Fig. 9 is a sectioned view, along a longitudinal plane of the sealing assembly of Figs. 7 and 8, once applied and integrated in the respective bottle, so as to seal it definitively;

Fig. 9A shows on an enlarged scale a zone of the section of Fig. 9;

Figs. 10A and 10B show a protection cover while it is removed from the sealing assembly of Fig. 9, in the use of the bottle sealed by it; and

Fig. IOC shows the area of the sealing assembly after the removal of the protection cover of Figs. 10A and 10B; and

Fig. 1 1 shows a variant of the sealing assembly of the invention;

Fig. 12 shows a variant of the sealing cap of the sealing assembly of the invention;

Figs. 13 and 13a show a variant of the locking nut of the sealing assembly of the invention;

Figs. 14a-14c show a variant of the intermediate cage of the sealing assembly of the invention;

Figs. 15-1 , 15-2, 15-3 show the sealing assembly of the invention, in the variant with the locking nut of Figs. 13 and 13a and the intermediate cage of Figs. 14a- 14c, during the various steps of the application of the sealing assembly on the bottle to be sealed.

Fig. 15a is a view on an enlarged scale of a zone indicated by a dotted and dashed circle in Fig. 15-3; and

Fig. 16 shows a further variant of the sealing assembly of the invention wherein the sealing cap is restrained in the intermediate cage by means of a glue or an equivalent adhesive substance.

Description of a preferred embodiment of the sealing assembly of the invention

Referring to the drawings and more particularly to Figs. 1 and 2, a sealing assembly, according to the invention, suitable for sealing bottles containing injectable sterile medicines or similar substances, is denoted overall by 10, while a corresponding bottle, containing an injectable sterile medicine F or a similar substance and sealed by means of such a sealing assembly 10, is denoted overall by 20.

The bottles 20 sealed with the sealing assembly 10 of the invention conform with unified standards and regulations, in particular as regards the dimensions both of the external diameter D of the respective containment body or container 20a, substantially cylindrical in shape, containing in fact the injectable sterile medicine F, and of the mouth 20b, of this containment body 20a, intended to be sealed during the packaging of the bottle 20.

For example these bottles 20, in the case wherein they conform to the standard 2 , have an external diameter D of the respective containment body 20a equal to 16 mm.

In detail, the sealing assembly 10 of the invention is essentially constituted by the following three parts:

a sealing cap 1 1 , also referred to simply as cap, suitable for being inserted and for sealing the opening or mouth 20b formed by the containment body 20a of the bottle 20;

- an intermediate retaining cage 12, suitable for housing and for cooperating with the cap 1 1 ; and

a locking nut 14, suitable for housing and for co-operating with the intermediate retaining cage 12, in order to block stably the various parts of the sealing assembly 10, once the bottle 20 has been sealed.

The mouth 20b, intended to be closed and sealed by means of the sealing cap 1 1 , is formed in an upper portion 20c, with a shape of a neck and for this reason also referred to simply as neck, of the containment body 20a of the bottle 20, and is described by a circular edge 20d, projecting externally, such as to form a circular undercut seat 20e in the area of the neck 20c.

Sealing cap

Referring to Figs. 3A-3C, the sealing cap 1 1 , essential part of the sealing assembly 10 of the invention, will now be described in detail.

The sealing cap 1 1 is a made of a soft material suitable for being perforated by the needle of a syringe, for example rubber or a similar material, and has a first upper portion, or head, 1 1a, cylindrical, of greater diameter; and a second lower portion, or stem, l ib, cylindrical, of reduced diameter, wherein the stem l ib has a slot 1 1c, having the function of allowing the evacuation of the vapours during a phase of lyophilisation of the injectable sterile medicine F contained in the bottle 20, as described herein below.

The head 1 1a, of greater diameter, of the sealing cap 1 1 , also forms, along its external cylindrical surface, a projection l i d, with circumferential development, suitable for co-operating with a corresponding recess, described herein below, formed in the intermediate retaining cage 12.

Moreover the head 1 1 a has on its upper surface, opposite the stem l ib, a series of projecting shapes including in particular a continuous circular ring projection, denoted by l l f, in the area of the sealing cap 1 1 intended to be perforated by a syringe, in the use of the bottle 20.

The stem l ib of the sealing cap 1 1 has in turn along its external cylindrical surface, at the sides of the slot 1 1 c, some projecting buttons or small areas, denoted by l ie, six in number as shown in Fig. 3 A, which are appropriately and uniformly distributed in a circumferential direction on the outer cylindrical surface of the stem 1 lb.

These projections l ie have in particular the function of holding the sealing cap 1 1 , and with it the entire sealing assembly 10, in a stable position and in line with the mouth 20b of the containment body 20a, during the packaging of the sealed bottle 20, as described in greater detail herein below. Referring to Figs. 3A-3C, an indication is given herein below of some preferred values of the dimensions which define and characterise the sealing cap 1 1 , included in the sealing assembly 10 of the invention, in the case where it is intended for sealing bottles conforming with the standard 2R, i.e. with external diameter D equal to 16 mm.

Intermediate retaining cage

Referring to Figs. 4 and 4A, the intermediate retaining cage 12 will now be described in detail.

The intermediate retaining cage 12 is made in plastic material and defines internally an internal cylindrical cavity 12a, suitable for receiving and for housing the head 1 l a of the sealing cap 1 1 , and in particular is constituted by:

a hollow cylindrical body, in turn constituted by a wall or base 12b, flat, and by a cylindrical tubular body 12c which extends in a longitudinal direction, along the axis of the intermediate retaining cage 12, from the base 12b; and by

- a crown, denoted overall by 13, which in turn is formed by a plurality or array of flexible tongues 13a, which are arranged around the axis of the intermediate retaining cage 12 and extend from the cylindrical tubular body 12c along the external surface of the retaining cage 12. The hollow cylindrical body 12c defines, along its internal surface facing onto the cavity 12a and adjacently to the base 12b, a recess 12d, with circumferential development, suitable for receiving and for housing the circumferential projection l id formed on the head or cylindrical portion 1 1a, of greater diameter, of the sealing cap 1 1.

A hole 12e is formed at the centre of the base 12b to allow the passage of a syringe, during the use of the bottle 20, as described in greater detail herein below.

Each tongue 13a of the crown 13 has at the tip a portion, denoted by 13b, of increased section in relation to that of the stem of the tongue 13a, wherein this portion 13b forms a tooth 13c, facing onto the internal cavity 12a of the intermediate retaining cage 12.

As can clearly be seen in Fig. 4a, the tooth 13c, tip, of each tongue 13a has a rounded and slanted profile 13c', in order to avoid jammings and therefore encourage the correct mounting of the intermediate retaining cage 12 on the edge 20d of the mouth 20b, during the application of the sealing assembly 10 on the containment body 20a of the bottle 20 to seal it, as described in detail herein below.

The profile 13c' has a degree of slant which can vary according to the dimension of the mouth of the bottle used, and for example can be defined by an angle β equal to 45° ± 20° in relation to a plane perpendicular to the longitudinal axis of the tongue 13a.

Moreover the various tongues 13a of the crown 13 form each one, in the area of attachment to the cylindrical tubular body 12c, a first notch 13d, turned towards the exterior of the retaining cage 12, and in the tip area, adjacently to the respective increased portion 13b, a second notch 13e, also turned towards the exterior of the retaining cage 12, wherein these notches

13d and 13e of the tongues 13a are positioned reciprocally aligned so as to define as a whole respectively a first and a second notch, with circumferential development, denoted by 13' and 13", which extend along a circumference on the external surface of the crown 13.

The intermediate retaining cage 12 has an initial undeformed configuration, or of mounting, shown in Fig. 4 and denoted by C, wherein the tongues 13a of the crown 13 are slightly inclined towards the exterior of the intermediate retaining cage 12.

In particular, in this initial configuration C, undeformed, the tips of the tongues 13a of the crown 13, inclined towards the exterior, define a circumference of diameter D 1.

Starting from this initial undeformed configuration, the crown 13 is provided in order to assume, at the end of the application of the sealing assembly 10 to seal the bottle 20, a final C" configuration shown in Fig. 9, wherein the tongues 13a are positioned parallel to the axis of the retaining cage 12, as described in greater detail herein below.

Locking nut

Referring to Fig. 5, the locking nut 14 is made up of an upper cover 14b, and a cylindrical hollow body 14c, connected one to the other, wherein the cylindrical hollow body 14c has a cylindrical internal cavity 14a, suitable for housing the base 12b and the cylindrical tubular body 12c of the intermediate retaining cage 12, and is in turn constituted by a flat base 14c', which is positioned adjacently to the cover 14b, and by a tubular part 14c" which extends in a longitudinal direction from the flat base 14c'.

The cover 14b of this locking nut 14 is made with plastic material, and is fixed on the flat base 14c' of the cylindrical hollow body 14c by means of a central projection 14b' of the cover 14b which is inserted in a hole formed on the flat base 14c' of the cylindrical hollow body 14c and subsequently riveted.

This cover 14b, of plastic material, is of the type commonly indicated by the term "flip off, i.e. it is of the type suitable for being removed manually, in the use of the sealed bottle, from the tubular body 14c, in order to uncover the area of the sealing cap 1 1 intended to be perforated by a syringe, as described in greater detail herein below.

The cylindrical hollow body 14c of the locking nut 14 is preferably made by deep-drawing of a thin sheet of metallic material, in particular aluminium, and has along its internal surface, facing onto the cavity 14a of the locking nut 14, and adjacently to the edge of the tubular part 14c", a projection or ridge 14d, with circumferential development, whose function will be explained in greater detail herein below in the description, which is obtained again by deep-drawing of the sheet of metallic material constituting the cylindrical hollow body 14c.

Process of packaging of a sealed bottle of the invention, containing an injectable sterile medicine

The features of the sealing assembly 10, according to the present invention, for the sealing of bottles containing injectable sterile medicines, will be made clearer by the following description, given with reference to Fig. 6, of the phases of packaging, in an automatic packaging line denoted overall by LCA, of a bottle 20, containing an injectable sterile medicine F, sealed with this innovative sealing assembly;

More particularly the process of packaging of the bottle 20 comprises a first phase (f- 1), wherein the containment body or container 20a of the bottle 20 is filled, in a corresponding filling station (a), with a medicine FL, in liquid form, by means of a tube T.

For example the container 20a is filled with lcc of medicine FL, which, in the case of a bottle conforming to the standard 2 with diameter D equal to 16 mm, means filling with liquid the container 20a up to a level of approximately 7-8 mm from its bottom. Subsequently the containment body 20a, once filled with the liquid medicine FL, is transferred via a conveying line, schematised in Fig. 6 with arrows LC, into a successive mounting station (b), where the containment body 20a receives the sealing assembly 10, during a corresponding mounting phase (f-2).

The sealing assembly 10, which is mounted on the containment body 20a in this mounting station (b), has in turn already been appropriately set up, with the respective three parts, i.e. the sealing cap 1 1 , the intermediate retaining cage 12 and the locking nut 14, in a pre-assembled configuration denoted by CP and shown in detail in Fig. 7.

The steps, via which the sealing assembly 10 is set up in this pre- assembled configuration CP, are the following.

In a first preliminary phase (fp- 1), with the intermediate retaining cage 12 appropriately set up so as to have the crown 13 orientated with the tip of the tongues 13a upwards, the sealing cap 1 1 is inserted inside the cavity 12a of the intermediate retaining cage 12, so as to house the circumferential projection l id, formed in the head 1 1a of the sealing cap 1 1 , in the corresponding seat 12d formed in the cavity 12a of the intermediate retaining cage 12.

In this way the sealing cap 1 1 is stably restrained inside the cavity 12a of the intermediate retaining cage 12.

Note how the insertion of the sealing cap 1 1 in the internal cavity 12a of the intermediate retaining cage 12 is encouraged and facilitated by the fact that the ends of the tongues 13a, of the crown 13, define towards the interior of the cavity 12a a diameter which is greater, even if by a little, than the diameter Φ of the circumferential projection l id formed on the head 1 1a of the sealing cap 1 1.

Therefore, after having turned over in a second preliminary phase (fp-2) the assembly formed by the sealing cap 1 1 and by the intermediate retaining cage 12, the locking nut 14 is mounted on the intermediate retaining cage 12, in a successive preliminary phase (fp-3), so that the circumferential projection 14d, projecting inside the cylindrical hollow body 14c, of the locking nut 14, engages the circumferential notch 13' formed on the external surface of the retaining cage 12, in the area adjacent to the base of the tongues 13a of the crown 13.

In this way the sealing assembly 10 takes on the preliminary pre-assembled configuration CP, as shown in Fig. 7.

The operation of mounting of the locking nut 14 on the intermediate retaining cage 12 and the consequent engaging of the projection 14d with the circumferential notch 13 ' causes a slight bending or closure, towards the interior of the intermediate retaining cage 12, of the tongues 13a, which in this way define with their tips a circumference of diameter D l ', corresponding to a deformed configuration C of the crown 13, as shown in Fig. 7, wherein this diameter Dl ' is slightly less than the diameter Dl corresponding to the initial undeformed configuration C of the tongues 13a.

In particular, in the case of the already mentioned standard 2 of the bottles, the tongues 13a of the crown 13 are configured so as to define with their tips, in the undeformed configuration C, a diameter D l equal to approximately 17 mm, and to bend, inwards, as indicated by the arrows f in Figs. 4 and 7, following the assembly of the locking nut 14 on the intermediate retaining cage 12, so as to define, in the deformed configuration C, a circumference having a diameter Dl ' of approximately 15.5-15.75 mm, in any case smaller than the standard diameter D, equal to 16 mm, of the containment body 20a of the bottle to be sealed, i.e. with Dl ' < D.

Now, returning to the mounting of the sealing assembly 10, in the pre-assembled configuration CP, on the mouth 20b of the containment body 20a, this mounting is performed by inserting the stem 1 lb of the sealing cap 1 1 in the mouth 20b until the projections l i e, formed on the external surface of this stem l ib, abut and stop against the flat surface 20d' of the edge 20d which describes and whereon the mouth 20b faces externally.

Therefore, in the mounting station (b), the sealing cap 1 1 is inserted only for a certain section in the mouth 20b, so as to leave uncovered a part of the slot 1 1c.

In this phase the fact that the projections l ie are distributed uniformly along the entire circumference, and not only on a restricted portion thereof, of the cylindrical surface of the stem 1 lb, ensures a correct positioning in a vertical direction, parallel to the axis of the mouth 20b, of the sealing cap 1 1 and therefore also of the sealing assembly 10 which, in the pre-assembled configuration CP shown in Fig. 7, is mounted on the containment body 20a.

Moreover these projections l ie mean that the sealing cap 10, and with it the sealing assembly 10, are held stably in the correct axial position wherein they have been inserted in the mouth 20b, and for example do not tilt during the movement of the bottles along the respective automatic packaging line LCA.

Therefore, during a phase (f-3), the containment bodies 20a, each one with a sealing assembly 10 partially inserted in the mouth 20b, are conveyed into a lyophilisation chamber CL, again schematised in Fig. 6.

It should be noted how, in this phase, as also in the later ones, the various bottles are handled and conveyed one in a row with the other along the conveying line LCA in a regular manner and without the risk of the sealing assemblies 10, pre-assembled, mounted on each one of them, coming reciprocally into contact, so as to cause anomalies in the regular functioning of the line of packaging of the bottles.

In fact, as already underlined previously, the tongues 13a of the crown 13 of the intermediate retaining cage 12 define at the tip, in the pre-assembled configuration CP of the sealing assembly 10, a circumference of diameter Dl ', which is smaller than the standard diameter D of the containment body 20a of the bottle to be sealed, i.e. with D l ' < D, so that the sealing assemblies 10, mounted on the containers 20a that are handled and conveyed one in a row and in contact with the other along the conveying line LC, are separated by a space S, as also shown with a dotted and dashed line in Fig. 7.

In the lyophilisation chamber CL, during a process phase (f-4), the bottles are subjected to a process of lyophilisation, of known features.

More particularly the bottles are subjected to a rapid swing or thermal shock which can range from -60 up to +40°C, and which determines first the solidification of the liquid phase contained in the medicine FL, and then its sublimation from solid phase to gaseous phase, with the consequent formation inside the container 20a of a porous compound, also called in jargon by the name "cake", made up of the lyophilised medicine F.

In this phase of process or lyophilisation (f-4), the vapours V which are produced due to the effect of the sublimation from solid phase to gaseous phase escape outside the container 20 through the slot 1 1c, formed in the sealing cap 1 1 , as indicated by arrows which schematise these vapours V in Figs. 6 and 7.

It should be noted how, in this phase of lyophilisation, the locking nut, being made at least partially in aluminium, or another metallic material, is able to withstand in an optimal manner the thermal shock of the process of sublimation without deforming and therefore without problems which could affect negatively the quality and tightness in time of the sealing.

Contrarily, the sealing systems currently applied are often entirely made with materials, such as plastics and the like, which tolerate poorly the thermal shock of the process of lyophilisation, and in particular due to this shock tend to deform and to lose their mechanical and strength features, with the risk of possible problems in terms of security and tightness of the sealing in time of the bottle.

Therefore, having completed the phase of lyophilisation, the containers 20a, containing the lyophilised medicine F, are hermetically closed and sealed inside the same lyophilisation chamber CL.

In particular this phase of sealing is performed in a corresponding sealing station (c) applying a pressure P from above on the locking nut 14 of each sealing assembly 10, so as to determine the complete insertion of the sealing cap 1 1 in the mouth 20b of the container 20a.

In greater detail, the pressure P, applied from above on the locking nut 14, determines, during a first phase (f-5), an advancement in axial direction downwards of the sealing assembly 10 for a section XI , as indicated by an arrow fl in Fig. 8.

In this first phase of insertion (f-5), the sealing assembly 10 maintains its pre-assembled configuration CP, with the locking nut 14 which continues to engage the circumferential notch 13 ", until the head 1 1a of the sealing cap 1 1 abuts against the surface 20d' of the upper edge 20d of the container 20a.

Therefore, when the head 1 1a of the sealing cap 1 1 comes into contact and abuts against the surface 20d' of the edge 20d, the pressure P determines the disengaging of the projection 14d from the circumferential notch 13', so that, with the sealing cap 1 1 and the intermediate retaining cage 12 stopped against the edge 20d, the locking nut 14, after being disengaged from the notch 13', slides relatively to the intermediate retaining cage 12 for a further axial section X2, during a second phase (f-6) and as indicated in Fig. 9, again in the direction of the arrow fl , until engaging with the projection 14d the circumferential notch 13" formed in the tip area of the tongues 13a of the crown 13 of the intermediate retaining cage 12. In this second phase (f-6), the locking nut 14, advancing axially for the section X2, engages with the respective cylindrical hollow body 14c, in aluminium, the tongues 13a of the crown 13 so as to flex them inwards, as indicated by arrows f2 in Fig. 9, and therefore close them stably and block them against the undercut seat 20e formed by the edge 20d of the mouth 20b.

Therefore the teeth 13c of the tongues 13a of the crown 13 close and engage the undercut seat 20e, so as to lock stably the sealing cap 1 1 , by now completely inserted, in the mouth 20b of the container 20a.

Note how the tip portion 13b of every tongue 13a is appropriately configured so as not to project towards the exterior from the cylindrical surface of the hollow body 14c of the locking nut 14, in the final configuration taken on by the crown 13, i.e. with the respective tongues 13a engaged in the undercut seat 20e to block the sealing cap 1 1.

Fig. 9 shows the sealing assembly 10 once fully assembled on the container 20a, with the sealing cap 1 1 completely inserted and blocked in the mouth 20b, and the intermediate retaining cage 12 in a final configuration C", wherein the tongues 13a are closed on the undercut seat 20e and arranged parallel to the axis of the mouth 20b.

In this final configuration of the sealing assembly 10, as shown in Fig. 9A, the central projection 14b' formed by the cover 14b of the locking nut 14 co-operates in contact with the continuous circular projection l lf formed on the upper surface of the head 1 1a of the sealing cap 1 1 , so as to protect and maintain sterile in time the area of the sealing cap 1 1 intended to be perforated by a syringe.

Therefore in a further phase (f-7) the various sealed bottles, denoted by

20-1 , 20-2, 20-3, etc., arranged in a row one with the other, are evacuated from the lyophilisation chamber CL in order to be subjected to other operations, such as for example inspection, labelling and the final packaging. In the actual use of the sealed bottles 20, the user removes manually, as shown with an arrow f3 in Figs. 10A - 10B, the plastic cover 14b from the locking nut 14, so as to determine the breakage of a series of small bridges 14e which connect the flat base 14c' of the circular hollow body 14c, in aluminium, of the locking nut 14, to the central projection 14b' of the cover 14b.

In this way, as shown in Fig. IOC, the area is uncovered of the sealing cap 1 1 corresponding to the circular projection l lf, so that the user can perforate this area with a syringe SI.

It is therefore clear, from what is described, that the present invention fully achieves the objects it had set, and in particular provides a new sealing assembly which is suitable for being advantageously applied and used in automatic lines of production and sealing of bottles containing injectable sterile medicines or similar substances, so as to produce also very positive effects on the cost of production of these sealed bottles.

Moreover the bottle sealed with the sealing assembly of the invention, in addition to being suitable for being packaged in a convenient and advantageous manner, ensures an optimal and stable sealing in time of the container containing in its interior the lyophilised medicine, as also any other similar compound or substance, in liquid form or in powder, prepared in a wide variety of ways.

Variants

Without detriment to the basic concept of the present invention, it is also clear that changes and further improvements may be made to the sealing assembly, described hitherto, and to its parts, without thereby departing from the scope of the same invention.

For example the rubber sealing cap may have a different configuration, also only limitedly to certain details, from the one described previously and shown in the drawings, and also dimensions different from those already indicated.

More particularly, according to a variant of the sealing assembly of the invention, denoted by 1 10 and shown in Fig. 1 1 , wherein the corresponding parts are denoted by reference numerals increased by 100 compared to the preferred embodiment 10 described previously, the sealing cap 1 10 is provided, along the external cylindrical surface of the respective head 1 10a, with a circumferential recess HOd, instead of a circumferential projection, as in the embodiment 10.

Correspondingly, in this variant 1 10, the intermediate retaining cage

120 is provided, in the respective cavity 120a, with a circumferential projection 120d, which is suitable for co-operating with the recess HOd to restrain the sealing cap 1 10, once inserted in the intermediate retaining cage 120.

Again, referring to Fig. 12, the sealing assembly of the invention can comprise a rubber sealing cap, denoted by 1 1 1 ' and alternative to those 1 1 and 1 1 1 described previously, which has above a projecting portion 1 15 in turn defining a circumferential recess or groove 1 15a, wherein this circumferential groove 1 15a has the function, co-operating with the other parts of the sealing assembly and in particular with the intermediate cage, of restraining the sealing cap in the same intermediate cage.

Moreover, according to another variant of the sealing assembly, denoted by 210 and shown in Figs. 13 and 13 A, wherein the parts corresponding to those of the previous embodiment 10 are denoted by reference numerals increased by 200, the cylindrical hollow body 214c in aluminium of the locking nut 214 has internally, in addition to a first protuberance or circumferential ribbing 214d, also a similar second protuberance or circumferential ribbing, denoted by 214d', suitable for co-operating with a corresponding circumferential notch or recess formed on the external surface of the intermediate cage 212, when the sealing assembly 210 is closed on the bottle 20 to be sealed.

Therefore, in this variant 210, the two circumferential protuberances 214d and 214d' of the locking nut 214 are provided for engaging the two corresponding notches formed on the external surface of the intermediate cage 212, so as to ensure a greater tightness and solidity of the sealing assembly 210, in the respective closed configuration as shown in Fig. 13a.

Again, according to a further variant of the intermediate cage, denoted by 312 and shown in Figs. 14a- 14c, wherein the parts corresponding to those of the embodiment 12 described previously are denoted by reference numerals increased by 300, the intermediate cage 312 is for example provided with a crown 313 formed by 10 tongues 313a, and also has, along the internal face of the base 312b, a plurality of ridges 315, for example 4 in number, extended along a circumference and suitable for co-operating with the head of the sealing cap.

For completeness Figs. 15- 1 , 15-2 and 15-3 show the sealing assembly of the invention, with the respective parts without, for reasons of simplicity, reference numerals, in the embodiment comprising the locking nut 214 of the variant of Figs. 13 and 13a, with two circumferential protuberances, and the intermediate cage 312, of the variant of Figs. 14a-14c, during the various phases of mounting of the sealing assembly on the bottle to be sealed.

More particularly Fig. 15-1 shows the sealing assembly, in the initial pre-assembled configuration, when it is rested on the mouth of the bottle to be sealed, with the sealing cap partially inserted in this mouth.

Fig. 15-2 in turn shows the sealing assembly, again in the pre- assembled configuration, during the phase of insertion of the rubber sealing cap in the mouth of the bottle due to the pressure applied to the sealing assembly.

Fig. 15-3 finally shows the sealing assembly of the invention in its final closed configuration, i.e. with the sealing cap completely inserted in the mouth of the bottle and the locking nut closed on the intermediate cage, and therefore with the two circumferential protuberances of the locking nut engaged with the two corresponding circumferential notches formed on the external cylindrical surface of the intermediate cage.

More particularly Fig. 15a shows how, in this embodiment of the sealing assembly, the tongues of the intermediate cage have a configuration wherein the respective tip teeth are staggered in an axial direction by a certain distance Δ in relation to the circumferential seat or notch which holds the corresponding circumferential protuberance formed on the internal surface of the locking nut, so as to ensure, in the final closed configuration of the sealing assembly as shown in Fig. 15-3, an optimal grip and tightness of the same tip teeth of these tongues in the undercut of the edge of the sealed bottle.

Still, according to a further variant of the sealing assembly of the invention, denoted by 410 and schematised in Fig. 16, wherein the parts corresponding to those of the previous embodiment 10 are denoted by reference numerals increased by 400, the rubber sealing cap 41 1 of the sealing assembly 410 can be restrained inside the intermediate cage 412, instead of by mechanical means and in particular, as described previously, by means of a circumferential protuberance formed on one of the two elements and suitable for co-operating with a corresponding groove formed on the other element, by means of an adhesive material, or a glue, or a putty or an equivalent substance, which is applied between the head 41 1 a of the sealing cap 41 1 and the internal surface of the flat circular base 412a or of the cylindrical body 412c of the intermediate cage 412.

For example, as schematised in Fig. 16, this adhesive substance or equivalent, denoted by AD, can be applied in the form of drops, during the phase of pre-assembly of the sealing assembly 410, on the flat upper surface of the head 41 1 a of the sealing cap 41 1 and/or on the flat internal surface of the circular base 412b of the intermediate cage 412.

These two parts 41 1 and 412 are then inserted one in the other and therefore brought into contact in the zone wherein this adhesive substance AD is present, so that, thanks to the interposition thereof, they remain stably attached one to the other.

Therefore the use of this adhesive substance AD allows both mounting of the sealing assembly 410 in the respective pre-assembled configuration, and maintaining it perfectly in line and centred in relation to the mouth of the bottle to be sealed, during the subsequent phases of application and closure of the sealing assembly 410 on the bottle to seal it.

It is underlined that this variant 410 has the important advantage of allowing the rubber sealing cap 41 1 to be restrained stably in the intermediate cage 412, during the phase of pre-assembly of the sealing assembly 410, and also of keeping correctly in line the sealing assembly 410 during the phase of application and closure on the mouth of the bottle to be sealed, without the rubber sealing cap having necessarily to have a special configuration, in the zone of the respective head 41 1a, or having to have a head specially designed in order to be suitable for being restrained in the intermediate cage.

In this variant of the invention it is therefore possible to use, in order to make the sealing assembly 410, usual rubber sealing caps, therefore without a special configuration, among those already in existence and usually available on the market.

Another point that deserves to be underlined concerns the need, particularly felt in the packaging of bottles containing medical substances, to avoid any potential source of pollution of the substance contained in the bottle.

In particular, in this regard, it is considered desirable by many experts to avoid as much as possible the use of sealing caps made of rubber, since this material appears to be a potential source of pollution and of the medical substance contained in the bottle sealed with such a rubber cap.

Therefore, in order to meet this need, in a further variant not shown in the drawings of the sealing assembly of the invention, the sealing cap of rubber can be externally protected with a film or a coating of inert material, so as to avoid any contact between the rubber sealing cap and the substance contained in the bottle.

Or it is possible to make the whole body of the sealing cap, instead of rubber, of an inert and non-polluting material, as for instance Teflon.

Again, advantageously, also from a constructive point of view of the sealing assembly, the sealing cap and the intermediate cage can be molded in a single piece of inert material, i.e. of Teflon, so as to avoid any possible pollution problem.

The sealing assembly was previously described, in the preferred embodiment 10 and in the others, with specific reference to a use for sealing bottles containing a lyophilised medicine, i.e. to bottles which receive and are filled preliminarily with a medicine, in liquid form, which is then lyophilised inside the bottle in a lyophilisation chamber, in which subsequently the bottles, once the lyophilisation process has been completed, are sealed inside the same lyophilisation chamber.

It is clear in any case that the concept of the present invention applies also for sealing assemblies intended to seal bottles, with mouths of different diameters, containing non-lyophilised medicines, and in general non-sterile, and therefore prepared in a different way, such as for example injectable substances and medicines, in powder form and/or the like. Obviously, in this case the sealing cap, corresponding to the sealing cap 1 1 of the embodiment 10, will not be provided with the slot for the escape of the vapours produced by the lyophilisation process, given that it performs solely the function of sealing hermetically the mouth of the container containing the injectable substance or medicine.

Correspondingly, the process of packaging of the sealed bottle does not provide for the intermediate passage of lyophilisation, so that the sealing assembly, once it has been rested and mounted on the mouth of the container containing the injectable medicine, is immediately pressed so as to cause the complete insertion of the sealing cap in the mouth of the container.