The invention relates to a tube as described in the initial section of claim 1. Furthermore the invention relates to the tube according to claim 1 in combination with a container with a built-in pump as described in the initial section of claim 10.
Within the pharmaceutical range many preparations are available as liquids. These preparations are in many cases stored in small or medium-sized containers, which are besides equipped with a tube which is suitable for pressing the preparation out of the container. In many cases the container is additionally provided with a built-in pump, typically built together with the tube, which is activated by hand force. In order to avoid undesired development of bacteria in the container a preservative may be added to the preparation. It is, however, desirable for certain types of preparations, as for instance eye drops, to avoid the addition of preservatives, as they may cause allergic reactions. In these cases a container with a pump is utilized, which prevents reflux of the preparation, so that impurities cannot be sucked back into the container. Several types of preservative-free pumps are available, which are characterized by the fact that bacteria cannot penetrate into the container. The weak spot is, however, the area from the valve of the pump and onwards to the spot where the drop comes out of the tube (the tip). In this case different manufacturers have chosen different solutions, which could for instance be represented by embedding of silver ions in the plastic in the area in question or mechanical valves preventing the particles from penetrating. By applying mechanical valves a remaining area will still exist (from the mechanical valve and onwards to the spot where the drop comes out of the tube), which is exposed to impurities. Besides the mechanical valve constitutes a cost-increasing element. Correspondingly embedding of silver ions is a cost-increasing process.
It is the objective of the invention to provide a self-closing mechanism, which prevents contamination with microorganisms, and which prevents impurities from penetrating into the tube in a container, and which concurrently may be manufactured economically.
This is, as stated, obtained in the characterizing part of claim 1 and 10.
Hereby a closing mechanism is obtained, which prevents contamination with microorganisms, and which prevents impurities from penetrating into the tube of a container. The closing mechanism may at the same time be manufactured economically. Besides the possibility is obtained of adjusting the velocity of the liquid, which is pumped out to a desired quantity. Finally pumping out of the liquid is enabled by way of a drop each time the pump is activated.
By a tube a tube intended for a liquid container should be construed. The tube may be cylindrically formed, but other geometries can also be utilized. For instance triangular tubes, quadrangular tubes, or multiangular tubes (from five and onwards). The tube may be straight or bent one or several times (for instance V-like shape, N-like shape, W-like shape etc.). The bending of the tube may besides follow a soft curve (for instance U-like shape or S-like shape). The tube can be provided with “concertina-bending”, so that the tube may be turned by a user. The tube may besides be provided with a sharpening at the mouth of the tube.
When the opening part in the other end contains a narrowing from the internal cross section of the inside to the opening cross section of the other opening across an axial distance longitudinally in relation to the tube, establishment of a closing mechanism is enabled by placing a bar of an elastic material in the tube, where the bar edges towards the narrowing. As the narrowing takes place over an axial distance longitudinally in relation to the tube, it is besides possible to focus a liquid which is pumped out and to determine the velocity of the liquid which is pumped out.
In case the narrowing is arranged proportionally with the axial distance, and in case a straight line with the narrowing has an angle (α) longitudinally to the tube, where α is less than 90 degrees, a particularly simple geometry is obtained, which facilitates the focusing of the liquid which is pumped out and eases the determination of the velocity of the liquid which is pumped out.
In case the opening part at the other end comprises a sharpening of the tube to an edge cross section of the narrowing, where the edge cross section is provided with an area which is smaller than that of the external cross section of the tube, and in which the edge cross section is provided with an area, which is larger than the area of the opening cross section of the other opening, a tube is obtained which prevents drops from adhering to the end of the tube after completion of the pumping of the liquid through the tube.
In case the flexible material is provided with resistant characteristics towards the liquid, it is avoided that the materials of the closing mechanism may combine with the liquid in the container or are solely dissolved in the liquid. This is of particular importance in case of pharmaceutical products.
In case the opening part in the other end comprises a barrier of silver ions and/or nanosilver particles, development of bacteria at the tip of the tube is prevented.
In case the tube comprises a protective cap adapted for fitting on the tube, where the protective cap is provided with covering means for covering of the other opening, the penetration of impurities to the tip of the tube is prevented.
In case the covering means comprise a barrier of silver ions and/or nanosilver particles development of bacteria in the protective cap is prevented, and thus also that development of bacteria may access the tip of the tube.
The invention will be described in further detail under reference to the enclosed figures, where
a illustrates a tube seen from the side according to the present invention, and
b illustrates a tube seen from the end according to the present invention, and
a illustrates an alternative embodiment of the other end of the tube seen from the side, and
b illustrates the tube from
a and 10b illustrate an embodiment of a core, and
In a preferred embodiment according to the invention the tube and container are used for pharmaceuticals and ophthalmic compositions, e.g artificial tears and compositions comprising hyaluronic acid used at cataract surgery.
In another preferred embodiment of the present invention the tube and container according to the invention give, when applied with ophthalmic compositions, a drop that is smaller than 50 μl, more preferably 15-30 μl, most preferably 15 μl.
In yet another preferred embodiment the tube and container according to the invention, when used with ophthalmic compositions, are used with the container vertically while dispensing the pharmaceutical, so that the drop comes into the eye in a horizontal direction. This makes the handling much easier, since the person using the container according to the invention can dispense the fluid with the head in an upright position and at the same time look into a mirror.
When using a container with the tube according to the present invention the tube is preferably held 0.5-1.5 cm, more preferably 1 cm, from the eye while dispensing an ophthalmic pharmaceutical.
In another preferred embodiment the tube is a silicone tube with a degree of hardness of 40-110 Shore. The degree of hardness of the tube may be varied depending on the viscosity of the liquid to be pumped out from the container via the tube. However, if it is not enough to vary the degree of hardness of the silicone, the hole in the tube may also be modified. A larger hole in the tube gives a slower velocity, with which the liquid comes out from the tube.
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The idea is to arrange a bar of a non-porous, elastic material inside the tube, so that it fills the tube longitudinally and concurrently possesses a diameter somewhat less than the internal diameter of the tube. The tube has been formed, so that at the opening a non-vertical surface in relation to the longitude of the tube is formed (that is an internal narrowing, for instance in the shape of a cone). This internal narrowing has the purpose of keeping the elastic bar in place and together with the elastic bar to form a closing mechanism. The angle (a) and the elasticity of the bar will together with the viscosity of the preparation determine the velocity, with which the preparation leaves the tube. The closing mechanism may accordingly be adapted to a given velocity for a given preparation by determination of the angle (a) of the narrowing and by determination of the elasticity of the bar. The closing mechanism functions by means of the force, with the aid of which the liquid leaves the valve inside the pump. The pressure from the liquid will compress the elastic material cross-sectionally and/or in a longitudinal direction, and the liquid will be pressed out of the opening of the tube. When the pressure falls again, the elastic material will revert to its original shape and thereby close the hole. The closing mechanism applies an elastic material, which will resist the ability of the microorganisms to adhere to the surface. The material can besides be provided with cast-in, active silver ions and/or nanosilver particles for greater safety.
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A first embodiment thus comprises fitting of a bar of a nonporous, elastic material inside the tube, so that it fills the tube longitudinally and concurrently possesses a diameter somewhat less than the internal diameter of the tube. The tube has been arranged, so that at the opening a non-vertical surface in relation to the longitude of the tube is formed (i.e. an internal narrowing, e.g. by way of a cone). The internal narrowing has been designed with the purpose of keeping the elastic bar in place and together with the elastic bar of forming a closing mechanism. The angle (α) and the elasticity of the bar together with the viscosity of the preparation determine the velocity, with which the preparation leaves the tube. The closing mechanism can accordingly be adapted to a given velocity for a given preparation when determining the angle (α) of the narrowing and when determining the elasticity of the bar. The closing mechanism functions by means of the power, with which the liquid leaves the valve inside the pump. The pressure from the liquid will compress the elastic material cross-sectionally and/or in a longitudinal direction, and the liquid is pressed out of the opening of the tube. When the pressure drops again, the elastic material will revert to its original shape and thereby close the hole. The closing mechanism applies an elastic material, which is resistant with respect to the microorganism's ability to adhere to the surface. The material can besides possess cast-in, active silver ions and/or nanosilver particles for greater safety.
a shows an alternative embodiment of the other end 902 of the tube seen from the side. The other end of the tube includes a narrowing 904 with a barrier part, which is constituted by a stiff core 906 fitted on the tube with fastening arms 918, core 906 edging towards an opening part, which is constituted by a cap 908 of an elastic material. The cap 908 is fitted across the narrowing and possesses an opening 910 with the same or less diameter as that of the core 906, so that the core blocks the opening 910 and thus penetration of impurities, e.g. bacteria, is avoided. The mentioned barrier effect is further enhanced by the application of an elastic material in the cap, so that the edge of the cap 908 presses against the edge on the core 906.
When a pump (not shown) is activated, the liquid is pumped out into the tube 902 into the clearance between the tube 902 and the bar 906. Where the bar 906 edges towards the cap 908 the liquid pressure will press the cap 908, so that the cap is deformed and thereby bears down, so that the liquid can pass further on out into the opening. When the pump is thereafter deactivated, the edge towards the cap 908 will again edge towards the edge on the core 906, thus blocking for liquid flow and impurities. On the figure the core 906 projects further than the tube 904, this will entail that a cavity 912 is formed between the cap 908 and the tube 904. The mentioned difference in length entails that after the fluid pressure a suction will occur and any remaining liquid on the tip 914 of the cap will be sucked back into the tube.
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The invention is further illustrated in the following examples, which, however, are not intended to limit the same.
Agar Plate Testing with Pseudomonas aeroginosa
Test Containers:
All tubes of the nine containers were inoculated for contamination for 3 min with Pseudomonas aeroginosa in 1.5 ml Eppendorf tubes with 1×105 cells/ml. Thereafter the tubes were dipped for 10 sec in 1×PBS (phosphate buffered saline) solution for washing.
Six drops from K1, Ag1 and Ag2 were dropped at time zero (T0) on TSB agar plates, plated and incubated at 28° C. The rest of the containers were placed in 100 ml sterile Duran bottles filled with 5 ml sterile 1×PBS and were incubated at 28° C.
After 4 hours (T4) six drops from K2, Ag3 and Ag4 were dropped on TSB agar plates, plated and incubated at 28° C. and after 6 hours (T6) the same procedure was repeated for K3, Ag5 and Ag6.
After incubation of all plates for 65 hours the plates were counted for CFU. CFU counts for all bottles are shown in table 1.
From the table it can be seen that the bacteria from the containers with tubes comprising silver ions and/or nanosilver particles are killed after 4 hours and 6 hours and that also the bacteria from the containers with tubes without silver ions and nanosilver particles are totally killed after 6 hours and almost killed after 4 hours. The results in the table also clearly demonstrate that the CFU counts at the start of the test are much lower when using tubes comprising silver ions and/or nanosilver particles according to the invention than for tubes without silver ions and nanosilver particles according to the invention.
Agar Plate Testing with Staphylococcus epidermidis
All tubes of the nine containers were inoculated for 10 min with Staphylococcus epidermidis (9142) in a micro plate with 1×106 cells/ml (200 μl/well) for contamination. Thereafter the tubes were washed once during 2 min in 1×PBS in a micro plate with 200 μl/well, followed by washing twice during 2 min in 1×PBS/Tween 20 in a micro plate with 200 μl/well, followed by washing twice during 2 min in 1×PBS in a micro plate with 200 μl/well.
Six drops from container K1, Ag1 and Ag4 were dropped at time zero (T0) on TSB agar plates, plated and incubated at 37° C. The rest of the containers were placed in 100 ml sterile Duran bottles filled with 5 ml sterile 1×PBS and were incubated at 37° C.
After 4 hours (T4) six drops from container K2, Ag2 and Ag5 were dropped on TSB agar plates, plated and incubated at 37° C. and after 6 hours (T6) the same procedure was repeated for container K3, Ag3 and Ag6.
After incubation of all plates for 12 hours the plates were counted for CFU. CFU counts for all bottles are shown in table 2.
From the table it can be seen that this test also verifies the function of the container and tube according to the invention.
Spectramax Testing with Staphylococcus epidermidis
Assay was performed according to Bechert et al., Nature Medicine Vol. 9, September 2000. Contamination with bacteria was with 500.000 cells/tube. Incubation was performed in minimal medium for 24 hours.
The proliferation assay reflected high antibacterial activity for the tubes with nanosilver particles according to the invention. The killing rate was 100% (bactericidal).
The general idea is thus that the end of the tube includes an opening part and a barrier part, respectively, where the barrier part edges towards the opening part, so that this will block the opening in the opening part. By at least forming the barrier part or the opening part in a flexible material, the pressing out of the liquid through the opening passing the barrier part is enabled. This happens after a deformation of at least the barrier part or the opening part. The design of the opening part and the barrier part, respectively, and the elasticity of the material will together with the viscosity of the preparation determine the velocity, with which the preparation leaves the tube. The closing mechanism can therefore be adapted to a given velocity for a given preparation. The closing mechanism functions by means of the force, with which the liquid leaves the valve inside the pump. The pressure from the liquid will cause deformation of the elastic material, so that the liquid can be pressed out of the opening of the tube. When the pressure falls again, the elastic material will revert to its original shape and the barrier part will block the opening in the opening part. The closing mechanism applies an elastic material, which is resistant with respect to microorganisms' ability to adhere on the surface. The material can besides be provided with cast in active silver ions and/or nanosilver particles for greater safety.
Number | Date | Country | Kind |
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PA 2002 00536 | Apr 2002 | DK | national |
PA 200201289 | Sep 2002 | DK | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/DK03/00241 | 4/10/2003 | WO | 5/31/2005 |