WO2004052434A1

WO2004052434A1 - Atomizer for liquids

Info

Publication number: WO2004052434A1
Application number: PCT/EP2003/013485
Authority: WO
Inventors: Peter Asp
Original assignee: Boehringer Ingelheim Pharma Gmbh & Co.Kg
Priority date: 2002-12-07
Filing date: 2003-12-01
Publication date: 2004-06-24
Also published as: AU2003289918A1; DE20218974U1

Abstract

The invention relates to a novel container (101) with a novel sealing flange (105), which is used as an atomizer container for atomizing a pharmaceutical liquid for application of a medical/pharmaceutical aerosol, whereby the active substance formulation is continuously kept under sterile conditions. The aerosols so produced can be applied for example nasally, orally, via the ears or to the skin. Nasal application is preferred. The atomizer is used to apply humectants, drugs and/or wound-healing substances.

Description

Atomizers for liquids

The present invention relates to a new container which is used as a container for an atomizer for atomizing a pharmaceutical liquid for applying a medical-pharmaceutical aerosol, the active substance formulation always being kept under sterile conditions. The aerosols generated in this way can be applied, for example, nasally, orally, via the ears or on the skin. Nasal application is preferred. Moisturizers, pharmaceuticals and / or wound healing agents can be applied via the atomizer.

With nasal sprays of the type described above, i.e. nasal sprays for constant and repeated use, it is necessary for the atomizers to be absolutely leak-tight so that biological impurities cannot be caused by leaks.

So there is e.g. Atomizers in which the active ingredient formulation is always under pressure from the outside environment. Such overpressure is used on the one hand to press the active substance formulation through the nozzle of the attachment and thus to generate the aerosol. In such cases, the use of pump attachments can be dispensed with. On the other hand, the overpressure means that no matter can penetrate into the storage vessel from the outside, thereby leading to contamination of the active substance formulation. If the attachment in such devices is a pump attachment for manual generation of the aerosol by means of pumps, these have the disadvantage that active ingredient formulation can flow out of the valve of the attachment even in the idle state, partially precipitate or condense on the valve and there is microbiologically contaminated. At the same time, it can also occur during spraying that the active substance formulation is deposited on the outlet valve or that small amounts of water condense there. Finally, the area between the pump attachment and the reservoir can be leaky.

All of these effects can result in the fluid in the reservoir or at the outlet valve and spout becoming biologically contaminated. WO02 / 34411 discloses an atomizer consisting of a pump attachment with oligodynamic means which prevent biological contamination in the storage container from occurring via the pump attachment. The storage container is an aluminum can. The security of such a system depends on the fact that there is absolute tightness at the joint between the aluminum box and the pump, even when exposed to changing temperatures. Due to the manufacturing tolerances of the flanged edge of such an aluminum can it has only been possible to create storage containers whose bottle necks have a flat or slightly convexly curved surface on the top, ie the surface of the neck that is perpendicular to the longitudinal axis of the container on the head side. The pump attachment is then placed on this surface. In order to achieve a sufficient sealing effect and to guarantee it in the long term, a permanently elastic rubber seal is necessary between the bottle neck and the pump attachment. These have the disadvantage that part of the sealing material can come out and thereby impair the pharmaceutical quality of the formulation to be applied. Inert plastics cannot be used as seals because they are too hard and not permanently elastic enough to solve the problem with the manufacturing tolerances of the previously customary and feasible can flange edges.

The object of the present invention is therefore to provide an atomizer which overcomes the difficulties known from the prior art.

In particular, it is an object of the invention to improve the sealing point between the reservoir and the pump attachment.

Another task is to ensure that the pump snaps properly onto the atomizer and that it fits securely onto the reservoir.

Another object is to prevent the seal from being displaced from its desired position in the case of such atomizers if the pump is placed slightly obliquely when it is applied to the storage container. Description of the invention

The object of the invention is achieved by a new, specially developed flanging of aluminum containers, in which a sealing line is created at the uppermost edge of the flanging edge, which seals the area between the aluminum can and the pump attachment instead of the previous sealing surfaces. A suitable plastic seal can be formed between the pump attachment and the sealing line.

The storage container according to the invention is a bottle made of aluminum, as shown in FIG. 1. Figure 2 shows the bottle neck enlarged with the flanging according to the invention. The storage container (101) consists of the bottle neck (102), the bottle belly (103) and the concave bottle bottom (104). The longitudinal axis of the bottle from the bottle belly to the bottle opening defines the terms above and below. Above or at the top is what points to the bottle opening, below or at the bottom is what points to the bottle bottom. The bottle neck has the flare shape (105) according to the invention. This is designed in such a way that the uppermost point of the bottle neck (107), which surrounds the bottle opening (108) in a ring, is designed as a sealing line.

The flanged edge according to the invention is idealized in cross section like a trapezoid, one of the two parallel base sides of which is formed by the outside of the flare lying parallel to the longitudinal axis and the other base side of which is formed by the inside of the bottle neck parallel to the longitudinal axis, both sides of the head side an inclined axis are connected, which rises from the outer jacket pointing towards the bottle opening. The base side formed by the inner wall of the bottle neck and the inclined axis enclose the angle alpha. The base side facing outwards and the inclined axis enclose the angle beta. The angle alpha is smaller - ie more acute - than the flatter angle beta. As a result, the corner of the inclined axis facing the bottle opening forms the highest point of the trapezoidal cross-section.

This shape of the flanged edge can also be described as follows: The inner wall of the bottle neck coming from the floor to the bottle opening following this, it kinks outwards at the top of the bottle neck by an angle of 180 ° - alpha from the longitudinal axis of the container towards the bottom. Ie the last straight piece of the inner wall of the bottle neck in front of the bottle opening (ie the longer side of the trapezium described above parallel to the longitudinal axis) and the kinked area (ie inclined axis of the trapezium described above) enclose the angle alpha. So bent, the flanging runs obliquely towards the bottom over a distance a before it bends again towards the bottom by an angle of 180 ° minus beta in order to now run a distance b parallel to the longitudinal axis of the container (i.e. the shorter side of the container parallel to the longitudinal axis trapezium described above). The angle beta is accordingly enclosed by the path section a and the path section b. At the end of the path section b, this is folded over in the direction of the container interior as usual.

The bottle flare thus appears in cross-section like a cylinder cut obliquely to the longitudinal axis, the high end of which lies at the bottle opening.

This high end forms the sealing line according to the invention, which runs in a ring around the container opening. This increases the tightness between the bottle neck and the seal of the pump attachment.

If necessary, an annular notch running perpendicular to the axis is formed in the vicinity of the bottle opening in order to be able to anchor a cap.

The bottle neck is generally narrower than the bottle belly, its outer diameter is preferably between 15 and 33 mm, particularly preferably 16 to 21 mm. In another embodiment, it is preferably 30 and 33 mm. The inside diameter is preferably 12 to 28 mm, particularly preferably between 14 and 16 mm. In another embodiment, it is preferably 24 to 26 mm. The bottle height is preferably 50 mm to 250 mm, particularly preferably 50 mm to 125 mm, most preferably 60 mm - 90 mm. The bottle belly preferably has an outer diameter of 20 mm to 100 mm, particularly preferably from 23 mm to 55 mm. The wall of the bottle has a thickness of 0.3 to 0.5 mm, preferably 0.37 to 0.41 mm, in the wall and neck area. The wall thickness of the floor area is 0.5 mm to 1.5 mm, preferably 0.8 to 1 mm.

The outside of the bottle can be painted and, if necessary, printed, the inside, including the bottle neck and its upper edge (106) can be coated with a synthetic varnish. It is preferably an epoxiphenol. The lacquer is advantageous in order to increase the corrosion resistance of the bottle to the active substance formulation and at the same time to prevent the active substance formulation from taking on a metallic taste.

The present invention also includes atomizers consisting of the aluminum storage cans according to the invention and a pump attachment, which preferably has the following features:

- A snap or crimp closure to be placed on the storage container;

- A pump channel that can pump liquid from the reservoir into a pressure chamber;

- A valve which is formed between the storage vessel and the pressure chamber;

- A riser pipe leading from the pressure chamber to a nozzle;

- A pressure control valve which is connected to the riser pipe, which is preferably formed in the riser pipe;

- a nozzle for atomizing the liquid;

- A trigger element, via which a piston can be actuated, which builds up the pressure required for nebulization in the pressure chamber;

- Air inlet points outside the pump tube or the riser pipe and air inlet paths from outside the pump attachment to the storage container;

- Oligodynamically active substances in and / or along the path taken by the liquid in the pump channel and / or riser pipe between the reservoir and the nozzle;

Means for sterilization along the path taken by the inflowing air, ie between the air inlet openings and the storage container, - And the aluminum storage bottle according to the invention with the flange according to the invention at the bottle neck to form a sealing line around the bottle opening.

In the atomizers according to the invention, the active substance formulation is always under normal pressure, and excess pressure can be dispensed with.

The pump attachment is preferably one as described, for example, in WO 97/18902 and shown in FIG. 3. The pump attachment (2) is firmly connected to the bottle neck and the flange edge (102) according to the invention via the snap closure (3). The inner edge of the snap closure (4) slides over the flange-shaped edge (105) of the bottle neck (102). There is a seal (5) between the bottle neck and the pump attachment, which is designed, for example, from plastics which emit no or only minor substances, preferably polyethylene. Liquid can be pumped from the reservoir into the pressure chamber (10) via a first pump channel (25). The pressure chamber (10) can be designed as part of the first pump channel (25) in its upper region. A ball valve (11) closes the path of the liquid through the first pump channel (25) into the pressure chamber (10). The pressure chamber (10) is part of the pressure cylinder (8). A piston (6) with a further axial pump channel (7) is located in the pressure cylinder (8). The piston (6) is held in the upper rest position by the spring (9) at a stop. The pressure chamber (10) is located between the piston (6) and the ball valve (11) and is connected to the upper pump channel (7).

The piston (6) has a smaller outside diameter than the inside diameter of the pressure cylinder (8), so that a gap (12) remains between the outside wall of the piston and the inside wall of the cylinder, which is sealed by the peripheral sealing body (13) of the piston. In the lower area of the pressure chamber (10), the pressure cylinder (8) has an area (14) with a larger inner diameter, in which the sealing body (13) has no sealing effect. A trigger element (15) is located on the piston (6) with the upper pump channel (7). From there, a riser pipe (16), which is connected to a pressure control valve (17), leads to a nozzle (18) in order to discharge the liquids to be atomized through the opening of the nozzle (18). The function of the upper pump channel (7) and the riser pipe (16) form a common riser pipe which connects the pressure chamber to the nozzle.

The pressure control valve (17) is connected to the riser pipe (16) in such a way that it is at least partially flushed by the liquid. The pressure control valve can be attached at any point within the common riser pipe, which is formed from the upper pump channel (7) and the riser pipe (16). In Figure 1, it is formed in the upper region of the riser pipe (16).

If the piston (6) is in the upper rest position, as shown in the drawing, the sealing body (13) seals the pressure chamber (10) from the

Opening (19) of the storage container.

The plunger (20) is fixed to the piston (6) in the region (21) and has a star-shaped diameter, so that there is a space between the

Pressure chamber (10) and the upper pump channel (7) remains.

In the rest position, the tappet (20) is far away from the ball valve (11), so that this valve is open with respect to the storage container if enough negative pressure is generated in the pressure chamber (10) and the valve is closed when the pressure there is correspondingly high is.

The liquid takes the following route through the pump attachment: First, it is pumped from the first pump channel (25) out of the storage vessel via the open ball valve (11) into the pressure chamber (10) and then reaches the pump channel (7).

From there, the liquid passes through the riser pipe (16) with that formed there

Pressure control valve (17) and finally reaches the nozzle (18).

In order to avoid biological contamination of the liquid in the storage container, oligodynamically active substances are formed along the path that the liquid takes from the storage chamber to the nozzle. These substances can be formed, for example, on the spring (9), on the wall of the upper pump channel (7) or the riser pipe (16), in the pressure control valve (17) and / or on the nozzle (18).

To equalize pressure in the storage container (101) after the discharge of liquids, air can flow into the device from the outside at points (23) and then penetrate into the storage container (101), as is shown, for example, by the arrow (22) in the Drawing is shown.

Means for sterilizing the incoming air are formed along the airway. These include, for example, sterility filters, membranes that are only permeable to air, bacteria-retaining materials, oligodynamically active substances, or microbicidal substances or combinations thereof. A sterility filter (24) is shown as an example in FIG.

As already stated, the pump attachment (2) is firmly connected to the bottle neck (102) by means of a snap lock (3).

Figure 4 shows a variant of Figure 1, in which the pressure control valve (17) is formed near the transition region between the upper pump channel (7) and the riser pipe (16). The result of this arrangement is that the area of the riser pipe (16) which lies between the upper end of the upper pump channel (7) and the pressure control valve (17) is greatly shortened compared to that of FIG. 3, whereas the area of the between the pressure control valve (17 ) and the opening of the nozzle (18) is significantly extended. As soon as the pressure control valve (17) is opened, the opening (26) is opened and the liquid from the lower region of the riser pipe (16), which is located in front of the pressure control valve (17), can pass it through the opening (26) in the upper area (26) of the riser pipe (16) flow. The nozzle (18) is covered by an attachable cap (27).

The advantages of the atomizer according to the invention are - in relation to the total weight of the filled atomizer, the low weight of the device itself, in the unbreakability of the reservoir, which is particularly true during the

Applying the pump attachment to the bottle neck is of great importance in the fact that the active substance formulation does not undergo any changes in taste due to the material of the storage container and in that the storage container is gas-diffusion-tight, so that the pharmaceutical stability of the active substance formulation, even after prolonged storage, is not caused by diffusing gas can be reduced in that the storage bottle is opaque in that a sealing line is formed around the bottle neck by the flange shape according to the invention, which increases the tightness between the storage bottle and the pump attachment.

Claims

claims

1. Bottle made of aluminum (101) consisting of a bottle bottom (104), a bottle belly (103) and a bottle neck (102), the bottle neck being crimped in such a way that the crimping in cross section is like a trapezoid, one of the two parallel base sides are formed by the outside of the flaring lying parallel to the longitudinal axis and the other base side is formed by the inside of the bottle neck parallel to the longitudinal axis, both sides being connected on the head side by an inclined axis which rises pointing from the outer jacket to the bottle opening (108).

2. Bottle made of aluminum according to claim 1, characterized in that the outer diameter of the bottle neck is between 15 and 33 mm, preferably 16 to 21 mm or 30 mm to 33 mm.

3. Bottle made of aluminum according to claim 1 or 2, characterized in that the inner diameter of the bottle neck is between 12 to 28 mm, preferably 14 to 16 mm or 24 mm to 26 mm.

4. Bottle made of aluminum according to claim 1, 2 or 3, characterized in that the wall of the storage container in the wall and neck area has a thickness of 0.3 to 0.5 mm, preferably 0.37 to 0.41 mm and in the bottom area has a thickness of 0.5 mm to 1.5 mm, preferably 0.8 to 1 mm.

5. Bottle made of aluminum according to claim 1, 2, 3 or 4, characterized in that the bottle neck has an annular notch running perpendicular to the axis.

6. Bottle made of aluminum according to claim 1, 2, 3, 4 or 5, characterized in that the storage container including the neck and the upper edge of the neck is painted on the inside.

7. Atomizer according to claim 1, 2, 3, 4, 5 or 6, characterized in that a seal, preferably made of an inert plastic, most preferably made of polyethylene, is formed between the bottle neck and the pump attachment.

8. Bottle made of aluminum according to claim 1, 2, 3, 4, 5, 6 or 7, characterized in that the bottle height is 50 mm to 250 mm, preferably 50 mm to 125 mm, more preferably 60 mm - 90 mm.

9. atomizer (1) for atomizing a liquid of a medical-pharmaceutical liquid kept under sterile conditions, not under pressure, consisting of a) a storage container made of aluminum (101) according to one of claims 1 to 8 with a non-pressurized liquid , and b) a pump attachment (2), which is attached to the neck of the storage container and is used for permanent atomization of the liquid by pumping, the pump attachment having the following features:

- A snap or crimp closure (3) for placement on the storage container (101);

- A pump channel (25) which can pump liquid from the reservoir into a pressure chamber;

- A valve (11) which is formed between the storage vessel and the pressure chamber;

- A riser pipe (7, 16) leading from the pressure chamber (10) to a nozzle (18);

- A pressure control valve (17) which is connected to the riser pipe;

- a nozzle (18) for atomizing the liquid;

- A trigger element (15), via which a piston (6) can be actuated, which builds up the pressure required for nebulization in the pressure chamber (10);

- Air inlet points (23) outside the riser pipe (7, 16) and air inlet paths (22) from outside the pump attachment to the reservoir;

- Means for sterilization (24) along the path that the incoming air takes, ie between the air inlet openings and the storage container.

10. Atomizer according to claim 9, characterized in that the pump attachment is a pump attachment as described in WO 97/18902.

11. Use of an atomizer according to claims 9 to 10 for atomizing pharmaceutical liquids

12. Use of an atomizer according to claims 9 to 10 for nasal application.