Technical Field

The invention relates to ^' a tube with a tube head and a container and to a method for manufacturing such a tube according to the preambles of the independent claims .

Background

In particular in medical applications pharmaceutical products are often stored in glass ampoules, glass vials or tubes. Tubes for storing pharmaceutical/medical products (in the following short: pharmaceutical products) usually consist of a tube head and a container, wherein the tube head is connected to the container by way of a shoulder. Figure 1 depicts such a known tube 1 in perspective view (Figure la) ) and in frontal view (Figure lb)) with a tube head 2, a container 3 and a shoulder 4. Figure lc) depicts a sectional view along the line B-B of the tube depicted in Figure lb) . The tube head 2 has a flow passage 5 with an orifice 6 through which the pharmaceutical product can be squeezed out if pressure is applied onto the container 3, i.e. if the container 3 is squeezed by a user. The orifice 6 of the tube head 2 can be closed by a cap (not shown) . Usually the tube head 2 is provided with an internal thread 7 and the cap is provided with an external thread that engages with the internal thread 7 when the cap is screwed onto the tube head 2. Often the tube head 2 is also provided with a closure sealing. With such a tube 1 the container 3 forms a single chamber for storage of a single pharmaceutical product. The end of the container 3 that is distal to the tube head 2 is typically closed by an end seam 8 in form of a welded seam. The quality of this end seam 8 is determined by parameters set during the manufacturing of the tube 1. Depending on the quality and the dimensions, in particular the width and the height of the end seam 8, the end seam 8 can withstand an inside pressure in the container 3 to a greater or lesser extent before it breaks, the inside pressure arising when the container 3 is squeezed.

During manufacturing of such a tube, the container is typically manufactured separately from the tube head with the shoulder. The . tube head and the shoulder are usually formed integrally. After manufacture of the container the tube head with the shoulder is attached to the container through welding or injection moulding.

To avoid permeation through the container, the container typically consists of a barrier material, such as a barrier laminate that comprises a barrier layer. Such a barrier is, however, often missing in the tube head and the shoulder. Hence, the container is typically of lower permeability, i.e. has a higher permeability barrier, than the shoulder, such that e.g. oxygen or water in form of water vapour may permeate through the shoulder into the container and may contaminate the pharmaceutical product.

To avoid permeation through the shoulder inlets that comprise barrier layers may be inserted during manufacture of the tube head and the shoulder. The tube head and the shoulder may also be provided with an additional coating/lamination for example by using plasma technology. Furthermore, the material of the tube head and the shoulder may comprise barrier plastics. Further, the material make-up of the tube head and the shoulder may be multi-layered. Such a multi-layered material makeup may be obtained by means of coextrusion and compression moulding. Moreover, so called scavenger additives may be added to the material of the tube head and the shoulder that can bind oxygen and water vapour.

However, the solutions for introducing some kind of permeation barrier into the tube head and the shoulder that are mentioned in the last paragraph are involved, and normally not such a low permeability can be achieved as for the container. Furthermore, for at least some of the mentioned solutions the complexity of the composite material that is used for the tube head and the shoulder is increased, which is disadvantageous from a regulatory point of view as it results in a higher risk of error and higher testing efforts for e.g. stability testing .

Often the pharmaceutical product consists of two different components, such as two different fluids, that are non-compatible and that have to be mixed for administration. Each component has to be stored separately to avoid degradation of the pharmaceutical product before administration. For example in medical applications often a dry component/substance has to be mixed with and thereby dissolved in a solvent for infusion into a patient. The dry component and the solvent have to be stored separately from each other until shortly before the actual infusion. To achieve this, a system may be used, wherein the dry component is stored in a first vial and the solvent is stored in a second vial. A transfer device is used to transfer the dry component from the first vial to the second vial and a disposable syringe is then used to administer the final pharmaceutical product consisting of the solvent with the dry component dissolved in it to a patient. Alternatively, a tube may be used that contains a further tube for the second component. Furthermore, a device may be used that has two compartments next to each other in the transverse direction, each compartment containing one component, wherein the two components are squeezed out of the compartments and into a separate mixing head and mixed therein to form the final pharmaceutical product, when pressure is exerted onto each of the two compartments. The transverse direction is herein defined as the direction perpendicular to the direction of flow.

The existing solutions for separately storing two components of a pharmaceutical product usually involve complex systems or devices, respectively, for mixing the two components or there are several handling steps necessary that have to be performed successively, which is time-consuming and hence cost-intensive.

Disclosure of the Invention

It is an object of the invention to provide a tube for separately storing two components, in particular two non-compatible components, of a pharmaceutical product that is easy in design and simple to use. It is a further object of the invention to provide a tube for separately storing more than two components of a pharmaceutical product. It is a further object of the invention to provide a tube in which one component can be stored without running the risk that this component is contaminated by a permeate such as oxygen or water vapour permeating through the tube head or the shoulder of the tube. It is a still further object of the invention to provide a method for manufacturing a tube according to the invention .

In order to implement these and still further objects of the invention, which will become more readily apparent as the description proceeds, a tube with a tube head and a container is provided, wherein the container is made of resilient material and wherein the tube head is connected to the container by way of a shoulder. The container is provided with an intermediate seam that divides the container into two chambers in the longitudinal direction of the tube. The intermediate seam blocks flow from one chamber to the other chamber in a flow-blocking, storing state of the tube. The intermediate seam is designed such that it breaks when sufficient pressure/force is exerted onto the chamber of the container that is adjacent to the intermediate seam and distal to the tube 5 head, thereby allowing flow from one chamber to the other chamber. The intermediate seam thus acts as predetermined breaking point between the two chambers. The intermediate seam is preferably obtained through welding, i.e. it is a welded seam that preferentially extends into the transit) verse direction of the tube. The longitudinal direction is defined as the direction of flow. The transverse direction is defined as the direction perpendicular to the longitudinal direction in frontal view of the tube of the invention. As typical the container is of lower perme- 15 ability, i.e. has a higher permeability barrier, with respect to permeates such as oxygen and/or water vapour than the tube head and the shoulder. Preferably the container consists of a barrier material such as a barrier laminate with at least one barrier layer.

2o In each of the two chambers a component of a pharmaceutical product can be stored. If the pharmaceutical product just consists of one component, i.e. no mixing of several components is required, than the one component is stored in the chamber that is adjacent to the 25 intermediate seam and distal to the tube head (also

called: distal chamber) . The one component can of course comprise several already mixed components that are compatible with each other. The intermediate seam provides a barrier for possible permeates such as oxygen and water 30 vapour that might permeate through the shoulder and/or the tube head into the container, such that permeates can not cross the intermediate seam and contaminate the one component of the pharmaceutical product and hence the pharmaceutical product. By distancing the one component 35 of the pharmaceutical product from the shoulder and by providing a barrier in form of the intermediate seam between the shoulder and the distal chamber that contains the one component, the permeation barrier characteristics of the container, which are usually much better compared to the permeation barrier characteristics of the tube head and the shoulder, can be fully used to avoid con ^¬ tamination of the one component through permeates such as oxygen or water vapour. No specifically designed tube head and/or shoulder made of complex material must be employed for avoiding contamination of the one component through permeates, i.e. the complexity of the overall material of the tube is reduced which facilitates analysis and testing of the tube, for example with respect to its stability, and reduces the risk that the tube might fail stability tests required for official/regulatory approval of the tube.

The tube of the invention is thus in particular applicable for storing a highly sensible fluid or paste-like pharmaceutical product for single-dose application, that needs to be protected against contact with oxygen and/or moisture absorption and/or moisture loss as best as possible.

Furthermore, the tube of the invention can be used to store two components, in particular two non- compatible components, of a pharmaceutical product that have to be stored separately, in that one component is stored in one of the chambers and the other component is stored in the other chamber, the chambers simply being separated by the intermediate seam. Each of the two components can of course comprise several already mixed components that are compatible with each other.

For mixing of the two components, pressure/force is exerted onto the chamber that is distal to the tube head such that the intermediate seam breaks and the component in this distal chamber flows into the chamber that is proximal to the tube head (also called:

proximal chamber) , with the two components becoming mixed in this proximal chamber for administration through the exertion of pressure/force onto the proximal chamber. Mixing of the two components and hence provision of the final pharmaceutical product is thus time-efficient and cost-efficient. Furthermore, material and/or device complexity is reduced and user-friendliness is increased in comparison to known devices/systems with two compartments for separately storing the two components that are employed for storing and mixing of the components. There may even be less risk for contamination of the final pharmaceutical product when mixing the two components. The tube of the invention moreover requires less transport capacity/shipping volume than known devices /systems and is - compared to systems with two glass vials - much less breakable.

In a preferred embodiment of the tube according to the invention the container is provided with two or more intermediate seams and the container is divided into several chambers by the two or more intermediate seams in the longitudinal direction. Thereby each intermediate seam is designed such that it breaks when pressure is exerted onto the chamber that is adjacent to it and distal to the tube head. This embodiment of the tube thus allows for the mixing of several components and hence for the administration of a pharmaceutical product consisting of several non-compatible components by exert- ihg ^~ pressure/fb ^~ fce orvEo ^" the ^{^} chambers , for- example by successively squeezing the chambers starting from the most distal chamber and moving up to the most proximal chamber, wherein "distal" and "proximal" refer to the location of the chamber with respect to the tube head.

The tube of the invention provides a simple and genuine barrier storage in particular for a pharmaceutical/medical product that consists of two or more components in the same or different phases (e.g. two liquid components or one liquid and one solid component such as a powder) that must be mixed first shortly before the application of the pharmaceutical product. The method for manufacturing a tube according to the invention comprises the steps of manufacturing a container and a tube head with a shoulder, for example through injection moulding, and of connecting the tube head to the container by way of the shoulder for example by welding the shoulder to the container. Then the container is provided with an intermediate seam that divides the container into two chambers in the longitudinal direction. The intermediate seam is in particular provided through welding, for example through ultrasonic welding, high-frequency welding, welding by heated jaws, or welding by means of a hot air stream. After provision of the intermediate seam the chamber that is adjacent to the intermediate seam and distal to the tube head is filled with a component of the pharmaceutical product. Then the container is closed at its end that is distal to the tube head preferably through an end seam, preferentially through a welded end seam obtained by welding. The intermediate seam and the end seam are designed and provided such that less pressure/force has to be exerted onto the chamber between the intermediate seam and the end seam to break the intermediate seam than to break the end seam, i.e. the intermediate seam breaks before the end seam would break.

If the pharmaceutical product to be administered by means of the tube of the invention consists of two components that have to be separately stored instead of one component, then before the provision of the container with the intermediate seam that part of the container that is proximal to the tube head and that is destined as proximal chamber is filled with the one of the components that is not - after provision of the intermediate seam - stored in the chamber distal to the tube head.

The container may be provided with several intermediate seams, for example through welding, thereby dividing the container into several chambers in the Ion- gitudinal direction for storing several, in particular several non-compatible, components of a pharmaceutical product .

The method for manufacturing the tube according to its invention has among others the advantage of being straight forward and relatively simple to perform.

Brief Description of the Drawings

Further advantageous features and applications of the invention can be found in the dependent claims as well as in the following description of the drawings illustrating the invention. In the drawings like reference signs designate the same or similar parts throughout the several figures of which:

Figure 1 depicts a tube with one chamber according to the state of the art in perspective view (Figure la)), in frontal view (Figure lb)) and as sectional view along the line B-B of Figure lb) (Figure lc) ) , and

Figure 2 depicts a tube according to the invention in perspective view (Figure 2a) ) , in frontal view (Figure 2b)) and as sectional view along the line A-A of Figure 2b) (Figure 2c) ) .

Figure 1 has been described in the introductory part of the description and it is referred thereto.

Mode(s) for Carrying out the Invention

Figure 2 depicts a tube 11 according to the invention with a tube head 12 and a container 13, wherein the tube head 12 is connected to the container 13 by way of a shoulder 14. The tube head 12 comprises a flow passage 15 with an orifice 16 through which a pharmaceutical product can be squeezed out. The tube head 12 is provided with an internal thread 17 for receiving an external thread of a cap (not shown) that can be screwed onto the tube head 12 for closing the orifice 16 and the flow pas- sage 15 for reasons of the protection. The container 13 is closed at the end that is distal to the tube head (also called: distal end) with an end seam 18, which preferably is a welded end seam.

The container 13 of the tube 11 of the invention is provided with an intermediate seam 19, which is preferably a welded seam, between its distal end and its proximal end, i.e. the end of the container 13 that is connected to the shoulder 14. The intermediate seam 19 divides the container 13 into two chambers 21, 22. Each chamber 21, 22 can contain a component of a pharmaceutical product. Each component can of course comprise several already mixed components that are compatible with each other. One chamber 21 is located between the intermediate seam 19 and the shoulder 14, i.e. it is proximal to the tube head 12 and adjacent to the intermediate seam 19 (also called: proximal chamber 21). The other chamber 22 is located between the intermediate seam 19 and the end seam 18, i.e. it is distal from the tube head 12 and adjacent to the intermediate seam 19 (also called: distal chamber 22) .

The intermediate seam 19 is designed such that it breaks if sufficient pressure is exerted onto the distal chamber 22. In comparison with the end seam 18, the intermediate seam 19 is designed such that less pressure exerted onto the distal chamber 22 is necessary for breaking the intermediate seam 19 than for breaking the end seam 18. If the overall length of the tube 11 depicted in Figure 2 is for example in the range of 10 cm to 12 cm then the height hi of the intermediate seam is preferably in the range of 0.1 cm to 0.3 cm and the width dl of the intermediate seam 19 is preferably in the range of 0.2 mm to 0.4 mm. For this example of a tube with a length in the range of 10 cm to 12 cm, the height h2 of the end seam 18 is preferably in the range of 0.3 cm to 1 cm, whereas the width d2 of the end seam 18 is preferably in the same range as dl, i.e. in the range of 0.2 mm to 0.4 mm. The height h2 is preferably (always) larger than the height hi. The intermediate seam 19 preferentially extends into the transverse direction in frontal view of the tube (confer Figure 2b) ) . It is preferable arranged at the centre of the container 13 in the longitudinal direction.

During manufacture of the tube 11 according to the invention both chambers 21, 22 or just one of the chambers 21, 22 may be filled depending on whether the pharmaceutical product that shall be administered by the tube 11 shall be composed of one or two components and in the latter case, whether the two components are compatible or not.

If the pharmaceutical product is obtained through mixture of two components, in particular two non- compatible components, than a first component is stored in the proximal chamber 21 and a second component is stored in the distal chamber 22. If a user then exerts sufficient pressure on the distal chamber 22, the intermediate seam 19 breaks thus allowing flow of the first component by way of the now opened/broken intermediate seam 19 into the proximal chamber 21, where it mixes with the first component, that is stored in the proximal chamber 21, to produce the pharmaceutical product. If the user then after this mixing exerts pressure onto the proximal chamber 21 the pharmaceutical product is

squeezed out of the tube 11 through the flow passage 15 and the orifice 16 of the tube head 12.

If the pharmaceutical product just consists of one component, then this component is preferably stored in the distal chamber 22. The one component can of course comprise several already mixed components that are compatible with each other. The intermediate seam 19 acts as a barrier such that possible permeates such as oxygen or water vapour that might permeate through the shoulder 14 and/or the tube head 12 are blocked and can not come into contact and contaminate the component in the distal chamber 22. To extract the one component and thus the pharmaceutical product from the tube 11 a user has to exert pressure onto the distal chamber 22 such that the intermediate seam 19 breaks and allows flow of the pharmaceutical product from the distal chamber 22 to the proximal chamber 21 by way of the now opened/broken intermediate seam 19. Exerting pressure onto the proximal chamber 21 after the pharmaceutical product has been moved to the proximal chamber 21 then squeezes the pharmaceutical product out of the tube 11 by way of the flow passage 15 and the orifice 16 of the tube head 12.

It is to be understood that while certain embodiments of the present invention have been illustrated and described herein, it is not to be limited to the specific embodiments described and shown.