AND DEVICE FOR MANUFACTURE THEREOF

The invention relates to a method and device for manufacturing a protected container and to a protected container which can be manufactured according to this method.

Containers for hazardous or strongly acting substances are for instance used in the medical world as injection vial or as container for instance for radioactive substances. Such containers are filled with a medicinal or radioactive substance and sealed with a seal which, if a liquid is used, can optionally be pierced with a hypodermic needle. The injection vial is generally also provided with a protective cap which must be removed before use. During production of the injection vials and other containers for hazardous or strongly acting substances, there is a great chance of such a substance getting onto the outer side of the vials. After filling and sealing the vials are therefore rinsed in order to remove this substance. Practice has however shown that the outer side of a vial is not always clean, i.e. free of contamination with an active substance. The rinsing has then not resulted in complete removal and residues of the active substance have been left. That residues of an active or strongly acting substance remain behind is sometimes no problem, but in particular cases the situation is different, such as with for instance cytostatics and antibiotics. It is thus known that cytostatics can absorb on glass. This can then result in hospital and pharmacy staff coming into undesired contact with these possibly highly toxic substances when handling such vials. In the case of antibiotics, contamination on the outside is undesirable because it can result in faster resistance of micro-organisms to the antibiotics in question when these micro-organisms come into contact with the vial or when the antibiotics in question come into contact with micro- organisms carried by hospital and pharmacy staff. That radioactive residues remain on a container is of course also undesirable.

In order to obviate the above stated problems containers have been developed which are provided with a protective envelope. The envelope is arranged after filling of the container and therefore prevents direct contact of a user with residues of a hazardous substance possibly adhering to the wall of the container. A method for arranging a close-fitting envelope round a container is for instance known from US 3 826059. A filled and sealed container is herein placed in a plastic envelope which is shrunk onto the container under the influence of heat. The envelope comprises a bottom part for

covering the bottom of the container, and an upright cylindrical part for covering the side wall of the container and a portion of a protective cap arranged on the container. According to the known method the container is inserted into an envelope of which one end is sealed, which poses difficulties, among other reasons because of the fact that air must be able to escape from the envelope while there is only limited space therefor. There is further a chance of air being enclosed between the envelope and the container wall when the envelope is shrunk onto the container.

The present invention has for its object to obviate the stated drawbacks and thus prevent the negative consequences thereof. For this purpose the invention provides a method for manufacturing a protected container for a hazardous substance, comprising the steps of a) providing a container filled with the hazardous substance with a side wall, a bottom and an access opening sealed by means of a sealing member, b) arranging a close-fitting envelope round the container, wherein the envelope comprises at least a first part and a second part which are arranged on respectively a first wall part and second wall part of the container, wherein both parts at least partially overlap each other. Possible contamination left behind on the outer side of the container after rinsing of the container is hereby encapsulated between the container and the tight-fitting envelope. Because the envelope according to the invention is arranged in at least two parts, it now becomes possible, depending on for instance the form of the container, to choose the form and position of the at least two parts on the container such that the envelope can be easily arranged and optimum protection is moreover provided. The parts can furthermore be chosen such that they follow almost faithfully the form of the container, whereby this latter can for instance be placed in stable manner on a surface. Due to the presence of the envelope a user is no longer exposed to toxic substances, because the user will not touch the container itself, but the envelope. Because the envelope fits closely round the container, the normal physical "feeling" with the container is preserved during use so that the further processing thereof remains the same, hi respect of developing resistance, micro-organisms here have no chance of coming into contact with residues of antibiotics on the outer side of the vial. An additional advantage is that the envelope provides for extra protection against breakage. If a container does nevertheless break, the envelope also ensures that the pieces of glass are held together and leakage of the hazardous substance is possibly prevented.

According to the invention the arranging of a protective envelope takes place after filling of the injection vial or other container, preferably after the step of sealing the container has also taken place. It is advantageous if the method is characterized in that the first part and/or the second part is self-adhesive and is arranged on respectively the first and second wall part of the container with the exerting of pressure. In this preferred embodiment the relevant part can be a sticker or any other self-adhesive body known to the skilled person. If desired, such a sticker can be provided with an identification, for instance in the form of a printing with text, a code, or another identification means.

In another preferred variant of the method the first part and/or the second part is manufactured from plastic and after arranging thereof are subjected to a heat treatment, wherein the first and/or the second part shrinks and is thus drawn close-fittingly against the container. Plastics which shrink under the influence of heat are per se known and can be chosen in accordance with the desired shrinking behaviour.

A particularly advantageous method is characterized in that the first part comprises a bottom part which is arranged against the bottom of the container, and wherein the second part comprises a sleeve which, after the first part has been arranged, is arranged over at least the whole side wall of the container and herein at least partially overlaps the bottom part along the peripheral edge of the bottom. The sleeve is here preferably manufactured from plastic, and slides round the container with little clearance and is then subjected to a heat treatment such that the sleeve shrinks and thus clamps close- fittingly round the container. It has been found that a container obtained with this preferred method can be set down in stable manner, provides optimum protection to the user and is furthermore manufactured easily and quickly.

In order to be able to achieve optimum protection, sleeve and bottom part must overlap at least partially. A particularly suitable method for realizing this in rapid and effective manner has the feature that the container provided with the sleeve is placed in a first position, wherein the sleeve does not extend further than the plane of the bottom part of the container, and that the container and/or the sleeve is subsequently placed in a second position wherein the container is displaced in axial direction relative to the sleeve and the sleeve extends beyond the plane of the bottom part of the container. In this preferred method the container and sleeve rest on a first shared support surface in the first

position, while in the second position the container comes to rest on a second support surface which is axially displaced relative to the first position and will generally be situated higher than the first position, although this is not essential according to the invention. In the second position the further extending part of the sleeve at least is preferably subjected to a heat treatment such that this part of the sleeve shrinks and thus clamps close-fittingly round the bottom part along the peripheral edge of the bottom. After arranging at least the further extending part of the sleeve, the remaining part of the sleeve is then subjected to a heat treatment, wherein this part shrinks and is thus also clamped close-fittingly round the container.

A further preferred method according to the invention comprises a first part in the form of a close-fitting sleeve which is arranged over at least the whole side wall of the container, and a second part which comprises a bottom part which, after the first part has been arranged, is arranged against the bottom of the container and herein partially overlaps the close-fitting sleeve along the peripheral edge of the side wall at the position of the bottom, hi this preferred variant the sleeve is preferably arranged over only a part of the height of the container, wherein the bottom part is folded upward over the peripheral edge of the container bottom. This preferred method has the additional advantage that a container is obtained with smooth underside, whereby it can be placed on its bottom surface in particularly stable manner.

It is further highly advantageous if the method according to the invention is characterized in that the container is kept within a temperature range such that practically no condensation occurs on the walls thereof prior to step b), and that the temperature of the hazardous substance does not rise above a predetermined limit value. This measure further enhances the protective action of the envelope and moreover ensures that the substance present in the container is not affected or becomes otherwise unusable. The method is preferably performed in a space held at practically constant temperature. It will be apparent that the above stated limit value of the temperature depends on the nature of the hazardous substance. The capacity of the cooling means can be adjusted hereto if desired. It is important for the invention that the arranging of the envelope takes place in a plurality of steps which are also spread through time. It has been found that in this way the temperature can be held below the designated limit value more easily.

The method according to the invention is manifested particularly well when the hazardous substance comprises a medicinal substance chosen from the group of cytostatics or antibiotics, and that the predetermined limit value of the temperature amounts to a maximum of 30 ⁰ C.

The invention also relates to a protected injection vial, comprising a filled and sealed injection vial with a side wall and a bottom, wherein a close-fitting envelope is arranged round the filled and sealed injection vial and wherein the envelope comprises a close- fitting sleeve and a bottom sticker, wherein the bottom sticker is arranged against the bottom of the injection vial and wherein the sleeve is arranged over at least the whole side wall of the injection vial and herein partially overlaps the bottom sticker along the edge of the bottom. The advantages of such an injection vial have already been described at length above and will not be repeated here. In a preferred embodiment of the protected injection vial the close-fitting sleeve comprises an extruded tube of a shrink foil. Such a sleeve is simple to manufacture. Yet a further preferred embodiment of the protected injection vial comprises a close-fitting sleeve in the form of a seamless extruded tube of a shrink foil. Such a sleeve ensures among other things that the container can be placed in stable manner on a surface. A stronger envelope is also obtained. The shrink foil is preferably manufactured from a vinyl chloride (co)polymer. Such (copolymers have the desired properties and are moreover flame-extinguishing.

The invention also relates to a device for manufacturing a protected container for a hazardous substance. The device comprises first and second means for arranging respectively a first and second part of a close-fitting envelope, and further at least one heat treatment space and cooling means, wherein the device also comprises transport means for displacing containers filled with a hazardous substance with a side wall, a bottom and an access opening sealed by means of a sealing member. The transport means for instance comprise one or more endless conveyor belts with which containers can be carried in continuous manner through the different units of the device.

In a preferred embodiment of the device the first and/or the second means comprise pressure means for arranging under pressure respectively the first and second part on respectively the first and second wall part of a container. The first and/or the second

means preferably also comprise heat treatment means for causing the first and/or the second part to shrink and thus draw close-fittingly against the container. In a very particular variant the first means comprise a labelling unit with which the first part in the form of a self-adhesive bottom part can be arranged against the bottom of a container with the exerting of pressure, and the second means comprise a sleeve arranging unit with which the second part, in the form of a sleeve brought to suitable length, can be arranged over at least the whole side wall of a container. Both a labelling unit and a sleeve arranging unit are per se known to the skilled person for other applications. A sleeve arranging unit is also referred to in the relevant field as sleeve unit or sleeving unit. It is usual in such units to supply the preferably seamless sleeve in practically flat form from a roll, and to then open this sleeve mechanically, for instance by guiding it over a mandrel. The sleeve is then pulled over a container in opened state and cut to the desired length by means of a cutting unit. The container is then provided with a relatively loose-fitting sleeve which, together with the container, rests on the same support surface, for instance a conveyor belt.

According to the invention the device is also provided with second means in the form of a heat treatment unit. In this unit the sleeve of a container is clamped close-fittingly round a container by submitting the sleeve to heat such that it shrinks. The heat treatment unit is provided for this purpose with heat supply means in the form of for instance an oven and/or one or more blow nozzles through which hot air is supplied.

A particular preferred variant of the device is characterized in that the second means further comprise positioning means with which a container provided with a sleeve can be placed in a first position, this such that the sleeve does not extend further than the plane of the bottom part of the container, and with which the container and/or the sleeve can subsequently be carried into a second position, this such that the container is displaced in axial direction relative to the sleeve and the sleeve extends beyond the plane of the bottom part of the container. The positioning means ensure that at least the further extending part of the sleeve comes to hang freely, whereby this part can optionally be manipulated and deformed in order to cover a portion of the container. The device is preferably provided for this purpose with blow nozzles directed at the further extending part of the sleeve, which blow nozzles can subject at least this part to a heat treatment in the second position of the container, such that this part of the sleeve

shrinks and thus clamps itself close-fittingly round the bottom part along the peripheral edge of the bottom. In such a case the sleeve is thus held to the container by the bottom part. For the time being the remaining part of the sleeve remains in relatively loose state round the container.

In a preferred embodiment the device is further provided with a heat treatment unit which is situated after the positioning means and which comprises blow nozzles which can subject the remaining part of the sleeve to a heat treatment, wherein this part shrinks and is thus clamped close-fittingly round the container. By providing the container with a close-fitting sleeve in at least two steps using the above stated preferred variant of the device, air inclusions are largely prevented and it is moreover ensured that the content of the container does not become too warm because the heat can be supplied in dosed manner to the container. In order to prevent the container reaching too high a temperature the heat treatment unit is preferably further provided with a conveyor belt with cooling.

The various aspects, features and advantages of the present invention will be further elucidated in the non-limitative description hereinbelow, with reference to accompanying figures, in which:

figure 1 shows a schematic front view of a device according to the present invention, figure 2 shows a cross-section of a protected container according to the present invention, figure 3 shows schematically the positioning unit of a preferred variant of the device according to the present invention, figure 4 shows schematically a detail of the positioning unit of figure 3, and figures 5A-5C finally show schematically the positioning platform in different positions.

Figure 1 shows a device 10 for manufacturing a protected container 1 for a hazardous substance 2. Device 10 comprises first means (not shown) and second means 11 for arranging respectively a first part 100 and second part 101 of a tight-fitting envelope, and further at least one heat treatment space 12 and cooling means (not shown). Containers 1 to be provided with a protected envelope are carried through the different

units of device 10 in continuous manner by means of transport means in the form of a plurality of mutually connecting conveyor belts (13a, 13b, 13c, ...). Containers 10 are filled beforehand with a hazardous substance 2 and comprise a side wall 3, a bottom 4 and an access opening 7 sealed by means of a sealing member 5. If desired, the container is also provided with a protective cap 6. In the preferred variant shown in figure 1 the first means (not shown) comprise a labelling unit with which the first part 100 in the form of a self-adhesive bottom part 100 can be arranged against bottom 4 with exerting of pressure.

Self-adhesive bottom part 100 can for instance comprise a bottom sticker which is taken from a continuous sheet and is arranged under a certain pressure with the adhesive side on bottom 4. The second means comprise a sleeve arranging unit 11 with which the second part in the form of a sleeve 101 brought to suitable length can be arranged over at least the whole side wall 3 of a container 1. In such a unit 11 a preferably seamless sleeve 101 is supplied from a roll 110 in practically flat form and then opened in mechanical manner (not shown in detail). Sleeve 101 is subsequently pulled in opened state over a container 1 and cut to the desired length by means of a cutting unit (not shown in detail). As shown in figure 4, container 1 is provided, after it has been carried through sleeve arranging unit 11, with a relatively loose-fitting sleeve 101 which rests on for instance a part of a conveyor belt (13a, 13b, 13c, ...). Device 10 further comprises positioning means 14 with which sleeve 101 and container 1 of a container 1 provided with a sleeve 101 can be displaced in axial direction relative to each other in order to leave free at least a part of the peripheral surface of sleeve 101. The axial direction herein correspond with direction X (see figure 2), which runs practically perpendicularly of the bottom of container 1. In the preferred variant shown in figure 3 positioning device 14 comprises a conveyor belt 141 with which containers 1 are transported in throughput direction Y and which carries a number of positioning platforms 142. Positioning device 14 is further provided with a second conveyer belt 143 which bears a number of gripping members 144 for fittingly receiving sealing member 5 or protective cap 6 of containers 1. As shown in more detail in figure 4, container 1 and sleeve 101 are supplied as according to position A. Using positioning platforms 142 container 1 and sleeve 101 are subsequently placed in a first position (position B) corresponding to a relative position of sleeve 101 and container 1, wherein sleeve 101 does not extend further than the plane of bottom part 100 of container 1. In

this position B which is elevated relative to supply position A, container 1 is received in a relevant gripping member 144 via its sealing member 5 or protective cap 6. Sleeve 101 is then carried into a second position C by lowering positioning platform 142, whereby container 2 is displaced in axial direction X relative to sleeve 101, and sleeve 101 extends beyond the plane of bottom part 100 of container 1. According to position C shown in figure 4, at least the further extending part of sleeve 101 comes to hang freely. Positioning means 14 are further provided with blow nozzles 145 directed at the further extending part of sleeve 101, whereby a heated medium, for instance air or an inert gas, can be blown. The free portion of sleeve 101 is hereby heated, whereby this portion shrinks and thus clamps close-fittingly round bottom part 100 along the peripheral edge of bottom 4. The peripheral portion of sleeve 101 herein remains in relatively loose-fitting state round container 1 for the time being. Container 1 is then displaced via conveyor belts (13a, 13b, 13c, ...) to a heat treatment unit 12 which, in respect of the throughput direction of containers 1, is situated after positioning means 14. Heat treatment unit 12 is per se known to the skilled person and can for instance be an oven which is heated with a suitable medium, for instance air or an inert gas. In order to enable targeted heating to be performed, heat treatment unit 12 comprises, if desired, blow nozzles (not shown) which are directed at the remaining portion of sleeve 101 and subjects this to a heat treatment wherein this portion shrinks and is thus clamped close- fittingly round container 1. In order to prevent container 1 reaching too a high temperature, heat treatment unit 12 is further provided with a conveyor belt 13c provided with cooling. This can for instance be air cooling and/or comprise liquid cooling, such as for instance water cooling.

The operation of positioning platform 142 is shown in detail in figures 5A-5C. Positioning platform 142 comprises a housing 400 for two nested (in other words coaxial) shafts (402, 502) which are displaceable in vertical direction X and the end surfaces of which form a support surface (403, 503) for a container 2 in respectively the first and second position. Shafts (402, 502) are vertically displaceable in direction X through vertical displacement of support rollers (408, 508) which support on running surfaces (406, 506) under the influence of spring force produced by springs (409, 509). By giving the running surfaces (406, 506) an ascending and/or descending profile as shown in figure 3, support rollers (408, 508) are carried respectively into a raised and/or lowered position in vertical direction X. In the preferred variant shown in figures 5A-5C

support roller 408 is vertically displaceable by pivotal connection 404 thereof to an arm 401 mounted on support body 400 and support roller 405. The connection runs via support body 407 which is rotatable around hinge 404. Figure 5A shows the supply position (corresponding to position A in figure 4). In this position support rollers (408, 508) are positioned relative to each other such that support surfaces (403, 503) lie in one plane. Figure 5B shows the first position (corresponding to position B in figure 4). In this first position support rollers (408, 508) are positioned relative to each other such that support surfaces (403, 503) still lie in one plane, but are raised relative to the supply position. The raised position is reached in that support roller 405 moves over a raised support surface 406, whereby support body 407 is rotated around hinge 404 in the indicated direction R. Finally, figure 5C shows the second position (corresponding to position C in figure 4). In this second position support rollers (408, 508) are positioned relative to each other such that support surfaces (403, 503) no longer lie in one plane but are displaced axially relative to each other. This is for instance possible by moving support surface 403 downward, whereby shaft 502 is released. Although support surface 403 is moved maximally downward (to the lowest position) in figure 5C, this is not essential. An intermediate position is also possible. The second position is reached in that support roller 405 moves over a support surface 406 which is lowered relative to position B, whereby support body 407 is rotated around hinge 404, this in a direction opposite to the indicated direction R. Support roller 508 is herein moved over a support surface 506 which is raised relative to the supply position.

Figure 2 shows a cross-section of a filled and sealed protected injection vial 1 according to the present invention. The protected injection vial 1 consists of a per se known glass injection vial with a side wall 3, a bottom 4 and an access opening 7. A medicinal liquid 2 is present in injection vial 1. If desired, the protected injection vial 1 is provided with a pierceable sealing member 5, for instance of rubber, and a protective cap 6, for instance of metal or plastic. On the outer side of injection vial 1 an envelope (101, 100) is arranged close-fittingly over practically the whole vial 1, leaving free the protective cap 6. Envelope (101, 100) comprises a bottom sticker 100 which covers bottom 4 of injection vial 1 and a sleeve 101 which covers side wall 3 and partially overlaps bottom sticker 100 along the edge of bottom 4. Sleeve 101 is preferably made of a transparent plastic, for instance a foil of PE, PP, PVC or the like. Bottom sticker 100 is preferably likewise made of a transparent plastic. It is recommended that bottom sticker 100 be

self-adhesive, although this is not essential within the scope of the invention. A suitable value of the thickness of sleeve 101 is 0.05 mm, but the value of the thickness can also be higher or lower. Bottom sticker 4 preferably has a thickness in the order of about 0.15 mm. For the sake of clarity the thickness of several components of protected injection vial 1 are exaggerated in figure 1.

The above described embodiment is only an illustration of possibilities of the present invention. Diverse changes and modifications are possible within the scope of protection of the invention as defined by the appended claims.

As a result of arranging the envelope, a possible contamination remaining on the outer side of the injection vial is encapsulated between the vial and the envelope. As a result a user is no longer exposed to toxic substances, because the user will not touch the injection vial itself, but the envelope. An additional advantage of arranging the envelope is that, if the injection vial breaks, the envelope will hold together the pieces of glass and will possibly prevent leakage of the medicinal or hazardous substance.