JP2809852B2 - Method and apparatus - Google Patents

Abstract

The application describes a method of introducing into a container a suspension or solution of a material in a propellant held under pressure, in particular a pharmaceutical material. The method comprises the steps of bringing a filling head (28) into communication with the container (C); introducing a quantity of such suspension or solution into the container through the filling head (28); introducing a quantity of high pressure propellant without any of the said material into the filling head (28), thereby to flush through any suspension or solution remaining in the filling head; and withdrawing the filling head from the container. An apparatus and a filling head (28) for carrying out the method are also described.

Description

Description: BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a method and a device for introducing a material to be dispensed in aerosol form and a propellant for this into a container. In particular, the present invention relates to introducing a drug into a container, and the following description focuses on this.
However, it will be appreciated that the invention is applicable to other materials.

Conventionally, drugs to be dispensed in aerosol form have conventionally been suspended in a mixture of at least two propellants, at least one of which is sufficiently high to be liquid at room temperature. It has a boiling point and at least one of the propellants has a boiling point low enough to be gaseous at room temperature.

For convenience, these are hereinafter referred to as liquid propellant or low pressure propellant, and gaseous propellant or high pressure propellant, respectively.
First, a drug is suspended in a propellant in a liquid state by a mixing operation. Each aerosol container is then partially filled with this suspension. A fixed amount of gaseous propellant is then introduced into each of the containers using either a cold or high pressure filling method. In the low-temperature filling method, the filling operation is performed at a temperature sufficiently lower than room temperature in order to keep the gaseous propellant in a liquid state.
Then, each container is closed with a closing member provided with an outlet valve.
The contents of the container can subsequently be dispensed through the outlet valve. In the high pressure filling method, a closure is attached to the container prior to introducing the gaseous propellant, followed by
The propellant is introduced into each container by press fitting into the container via an outlet valve. During this operation, the outlet valve effectively acts as an inlet valve.

There is currently no satisfactory method for filling a container with a suspension or dissolved solution of a drug in a one-component or multi-component propellant which is gaseous at room temperature. One object of the present invention is to provide such a method,
It is to provide an apparatus for performing such a method.

1 and 2 are schematic diagrams of a typical known device for introducing a drug and a two-component propellant into a container.

FIG. 1 shows the introduction into a container C of a suspension of a drug in a liquid propellant. Vessel 1 has a bulk supply of suspension, which is pumped by pump 2 and upturn valve 3
Through the metering cylinder 5 provided with a hole 5. From here the suspension is sent to the filling head 8. In the absence of a filling operation, the suspension flows through the head 8 to the check valve 9 and from there back to the container 1. That is, the suspension is constantly circulating. When a certain amount of suspension is introduced into the container C, the container is placed under the head 8 and the valves 3 and 9 are closed. The pneumatic cylinder 6 is then actuated and the piston is depressed to release the pressure of the suspension trapped between the valves 3 and 9 by opening the valve of the filling head 8 and the suspension is filled into the container C. Increased to a value sufficient to be sent from. The valves 3 and 9 are then opened and the valve of the filling head 8 is closed, at which time the piston in the cylinder 6 is raised to its initial position and the cylinder 4 is filled with the container 1. The connection and removal of the filling nozzle from each container is performed by a cylinder device 7. The filling head 8 is operated only when feeding with the container C.

A suspension in which a drug is suspended in a liquid propellant is introduced into the container C by the apparatus shown in FIG. 1, and then the aerosol valve is caulked and fixed to the can C. 2 operates to introduce a gas propellant into the can C. The device of FIG. 2 is formed of substantially the same components as the corresponding components of FIG. 1, except that there is no component corresponding to the check valve 9 and no recirculation takes place. The components in FIG. 2 are provided with reference numbers obtained by adding 10 to the numbers corresponding to the reference numbers used in FIG. Container 11 contains only the gas propellant that has been pressurized enough to keep it liquid,
Contains no drugs.

When the apparatus shown in FIG. 2 is operated, the filling head 18 is moved to the container C.
A small amount of gaseous propellant escapes with each lift. If the loss of propellant in this method is small, it is almost insignificant.

However, this feature in the operation of the device of FIG.
When used to introduce a suspension or dissolved solution of a drug in a high-pressure propellant into a container, this is extremely unsatisfactory. If the container 11 contains such a suspension or solution, a large amount of suspension or solution escapes each time the filling head 18 is lifted from the container C. This would pose a danger to the personnel engaged in this operation and would result in significant financial losses if the drug involved was expensive. In addition, the escaped drug tends to adhere to the periphery of the device and to the exterior of the container itself, causing cleaning problems. The first of these problems can be avoided in principle by surrounding the device of FIG. 2 with an exhaust, but this is rather expensive. The other two problems cannot be avoided with such an exhaust system.

[Specific description of the invention]

According to the present invention, the state where the pressure is applied is maintained,
A method of introducing a suspension in which a material is suspended in a propellant or a solution in which a propellant is dissolved into a container, wherein the filling head is communicated with the container, and a certain amount of the suspension or solution. In order to wash out the suspension or solution remaining in the filling head through the step of introducing into the container via the filling head, a certain amount of a high-pressure propellant containing no material at all while the filling head is in communication with the container. A method is provided having a step of introducing the filling head and a step of retracting the filling head from the container.

According to the present invention, the state where the pressure is applied is maintained,
A device for introducing a liquid in which a material is suspended in a propellant or a dissolving solution in which a propellant is dissolved into a container, and a filling head which is connected to or removed from the container. An apparatus for supplying a fixed amount of high-pressure propellant to the filling head without any material, the device comprising: An apparatus is provided wherein a completely free propellant stream is configured to wash away any suspension or solution remaining in the fill head.

Furthermore, the present invention provides that the pressure is maintained
A filling head for use in introducing a suspension of a material in a propellant or a dissolution solution in a propellant into a container, the head being in communication with the container during use. Outlets and first outlets each communicating with the outlets through a common passage.
And a second inlet, during use, a propellant containing material and a propellant not containing material are respectively introduced through these inlets, and fluid flowing into either inlet flows out of the other inlet. A filling head is provided having a device for selectively closing the first and second passages so as not to be clogged.

In all aspects of the invention, it is advantageous and convenient if the propellant, which is neither suspended nor dissolved, is the same propellant as the propellant containing the drug. Advantageously, the propellant is 1,1,1,2 tetrafluoroethane, known as propellant "134a".

Preferably, the material to be filled into the container is a drug, such as salbutamol or beclomethasone dipropionate.

Embodiments of the present invention will be described below as examples with reference to the accompanying drawings.

EXAMPLE The device according to the invention shown in FIG. 3 has a practically similar combination as the device of FIGS. 1 and 2, but has a common filling head of a novel design. The components shown in FIG. 3 have reference numbers obtained by adding 20 or 30 to the numbers corresponding to the reference numbers used for the components shown in FIG. The container 21 contains a suspension of the drug in a high-pressure propellant, and the container 31 contains a single supply of the same propellant without the drug alone, i.e., in a state in which the drug is not suspended. I have. In this embodiment, the container 31 contains the same propellant,
Of course, different types of high pressure propellants may be used. Further, the container 21 may contain a solution of the drug instead of the suspension.

FIGS. 4 (a) to 4 (d) show the filling head 28 used in the apparatus of FIG. 3 in more detail and in an enlarged view. The head has a substantially cylindrical body 40, the lower end of which is adapted to engage on the upper end of the aerosol container C in use. A tubular member 43 is slidably mounted in the main body 40. The tubular member 43 has a large-diameter base portion.
44, a small diameter body portion 45, and a smaller diameter neck portion 46. As used herein, "large diameter" and "small diameter" relate to diameter.

The neck portion 46 of the tubular member 43 extends through the base of the downwardly facing cup 47, the wall of which surrounds the body portion 45. Thus, the body portion 45 can slide within the cup 47.

The base portion 44 of the tubular member abuts a lip 50 extending inwardly of the body 40. A lip 51 extending outwardly of the cup 47 rests on an inner shoulder 52 of the body 40.

The tubular pillar 55 is screwed to the main body 40 so that its lower edge engages on the lip 51 of the cup 47. Thus, the pillar 55 fits around the wall of the cup 47.

Ring 56 is threaded into pillar 55 for mounting above cup 47. Neck of tubular member 43
46 is designed to just enter the ring 56. A sliding seal 58 fits between the ring 56 and the neck portion 46. Further, rubber O-ring seals 59 and 60 are
Member 43 into which the nozzle of container C fits between
(See below).

The ring 56 constitutes an upwardly tapered seat 62 for a correspondingly formed plug 63. The plug 63 is pressed against the seat by a compression spring 64, and the upper end of the spring 64 is a pillar.
It abuts the 55 inward lip 65. Above the ring 65 there is an opposed inlet 69 connecting the outside and the inside of the pillar 55, and thus inside the tubular member 43, i.e. the container.
70 are provided.

The inlet pipes 72 and 73 are fitted in the inlets 69 and 70, respectively,
-Sealed by ring seals 74, 74 '.

Between the inlets is provided a ball bearing 75 which engages with one of the O-rings 74, 74 'to form a valve. As described below, the ball bearing 75 is pressed against an O-ring 74 to seal the inlet 69 or pressed against an O-ring 74 'to seal the inlet 70.

The pillar 55 has a circular seat (not shown) of a piston which acts to push the mating head down onto the container C at the inlet 69,
Form above 70.

Inlet 69 is connected to a conduit that carries the suspension from metering cylinder 24 to check valve 29. The inlet 70 is connected to the outlet of the metering cylinder 34 containing the propellant.

In the rest state, the suspension S flows along the line from the metering cylinder 24 to the check valve 29 without entering the pillar 55. The suspension entering the pillar 55 is
Is blocked by the ball bearing 75 pressed against the O-ring 74 by excess pressure of the propellant P in the pipeline from If it is desired to introduce a certain amount of suspension into the container through the head 28, close the valves 23 and 29 and activate the cylinder 26 to move the piston downward, as described below. .

At this stage, the filling head 28 has been moved down onto the container C as shown in FIG. 4 (b). The nozzle of the container abuts the O-ring seal 60 and as the head is lowered, the nozzle pushes the tubular member 43 into the cup 47 and ring 56 until the lip 50 of the body 40 abuts the rim of the container. In this position, the neck portion 46 of the tubular member 43 is
The plug 63 is pushed out of the seat 62 against the action of the spring 64. Penetration between the interior of the pillar 55 and the tubular member 43 is now possible.

The increase in the pressure of the suspension in the metering cylinder 24, which causes the operation of the cylinder 26, is sufficient to overcome the propellant force acting on the ball bearing valve 75, so that the suspension flows from the inlet 69 through the pillar 55 And through the interior of the tubular member 43 into the container. Suspension pressure ball bearing valve 75
To the O-ring 74 ', the inlet 70 remains closed. Thus, the suspension cannot pass from the inlet 69 to the inlet 70 and does not contaminate the inlet 70.

The next step in filling the container is to pass a quantity of propellant without drug suspension through the interior of the pillar 55 and the tubular member 43 to the head 28 and, thus, into the container. This is done by closing valve 33 and operating pneumatic cylinder 36. The increase in propellant pressure that causes this is sufficient to move the ball bearing valve 75. Propellant cannot pass from the inlet 70, which is open in this case, to the inlet 69. This is because the ball bearing valve 75 is pressed against the O-ring 74. This position is shown in FIG. 4 (c).

By introducing the propellant through the inlet 70 with the head 28 resting on the container, the pillar 55 and the tubular member 43 are introduced.
Rinse the remaining suspension inside. Therefore, after the filling operation is completed, when the head 28 is lifted from the aerosol container as shown in FIG. 4 (d), almost all of the material escaping from the lower end of the head is composed of the propellant, and the agent escapes into the surrounding atmosphere. do not do.

FIG. 5 illustrates a variation of the filling head 28 to be used in the apparatus of FIG. The head shown in FIG. 5 has a substantially cylindrical body 80, the lower end of which is adapted to engage the upper end of an aerosol container (not shown in FIG. 5) during use. . A ring 81 is slidably mounted in the main body 80 in the length direction. Ring 81 has an inward flange 82
And the lower end of the tubular member 83 rests on this fringe. The upper part of the tubular member 83 is surrounded by a downwardly facing cup 84. The cup 84 is surrounded by an annular lower portion of the pillar 85. This annular portion is screwed into the body 80 to hold the cup 84 in place and the O
A seal is provided by a ring seal 86 and a sliding seal 87; The annular member 83 is pressed by a compression spring 88 into engagement with the flange 82. The upper end of the spring 88 is in contact with the surface of the cup 84.

Pillar 85 has a pair of opposed inlets 89 and 90. Inlet 89 is connected to a conduit that carries the suspension from metering cylinder 24 to check valve 29. The inlet 90 contains the propellant and is connected to the outlet of the metering cylinder 34. Entrance 89
And 90 communicate with the interior of the tubular member 83 via poppet valves 91 and 92 which are pressed to the closed position by compression springs 93 and 94, respectively.

As in the embodiment of FIG. 4, in the rest state,
The suspension flows along the conduit from the metering cylinder 24 to the check valve 29 without entering the interior of the tubular member 83. The suspension of the suspension from entering the inside of the tubular member 83 is prevented by the valve 91. If a certain amount of suspension is to be introduced into the container via the head 28, the valves 23 and 29 are closed and the cylinder 26 is actuated to move the piston downward in the cylinder. This increase in the pressure of the suspension in the metering cylinder 24 due to the movement of the piston is sufficient to overcome the force of the spring 93 that holds the valve 91 closed, so that the suspension passes from the inlet 89 to the tubular member. It flows into the container through the interior of 83. The valve 92 remains closed and the effectiveness of the seal provided by the valve 92 is increased by the head 95 of the valve 91 engaging the head 96 of the valve 92. Thus, the suspension cannot pass from the inlet 89 to the inlet 90 and does not contaminate the inlet 90.

The next step in filling the container is to introduce a quantity of propellant without any drug suspension through the tubular member 83 into the head 28 and thus into the container, as in the previous embodiment. This is done by closing valve 33 and activating pneumatic cylinder 36. The resulting increase in propellant pressure is sufficient to open valve 92 and inject propellant through head 28. Propellant cannot pass from inlet 90 to inlet 89 due to the operation of valve 91.

By introducing the propellant through the inlet 90 with the head 28 resting on the container, the suspension remaining in the tubular member 83 and in the space directly above the tubular member is washed away. Therefore, even in this embodiment, when the head 28 is lifted from the aerosol container after the filling operation is completed, almost all of the material that escapes from the lower end of the head is the propellant, and the medicine does not escape.

[Brief description of the drawings]

1 and 2 are schematic diagrams of a typical known device for introducing a drug and a two-component propellant into a container. FIG. 3 is a schematic diagram of a device of the present invention; 4 (a) to 4 (d) are views of one embodiment of a filling head used in the apparatus of FIG. 3, and FIG. 5 is a diagram of a filling head used in the apparatus of FIG. FIG. 6 is a diagram of another embodiment of the head. 21,31 ... container, 28 ... filling head, 40 ... body, C ...
... aerosol container, 43 ... tubular member, 44 ... base part, 45 ... body part, 46 ... neck part, 47 ... cup, 50, 51 ... lip, 52 ... inner shoulder, 55 ... Tubular pillar, 56… Ring, 58… Sliding seal, 59,60… O
-Ring seal, 62 ... seat, 63 ... plug.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-54-126955 (JP, U) (58) Fields surveyed (Int. Cl. ⁶ , DB name) B67C 3/00-11/06 B65B 31 / 04

Claims (10)

(57) [Claims] 1. A device for filling a container with a suspension or solution in which a desired substance is suspended or dissolved in a propellant under pressure, wherein the container can be in communication with the container, and A filling head that can be removed from the container, a means for supplying a fixed amount of the suspension or solution to the filling head, and a fixed amount of high-pressure propellant alone containing no desired substance. Means for supplying the suspension or solution and the propellant alone; a common passage for the suspension or solution and the propellant alone; an inlet for the suspension or solution; and an inlet for the propellant alone. And a valve member, wherein each of the inlets communicates with the common passage, and wherein the valve member communicates with the common passage only at one of the inlets at any one time. To the suspension Or between the position for closing the inlet for the solution and the position for closing the inlet for the propellant alone, so that when the inlet for the propellant alone communicates with a common passage, the desired substance can be removed. The device characterized in that the propellant, which does not contain any, is able to wash away any suspension or solution remaining in the filling head. 2. The apparatus according to claim 1, wherein said valve member is a spherical member. 3. A device for filling a container with a suspension or solution in which a desired substance is suspended or dissolved in a propellant under pressure, wherein the device is capable of communicating with the container and A filling head that can be removed from the container, a means for supplying a fixed amount of the suspension or solution to the filling head, and a fixed amount of high-pressure propellant alone containing no desired substance. Means for supplying the suspension or solution and the propellant alone; a common passage for the suspension or solution and the propellant alone; an inlet for the suspension or solution; and an inlet for the propellant alone. Wherein each inlet communicates with the common passage and the inlets face each other, and each inlet has a valve member for opening and closing the respective inlet, and the respective valve member Are adjacent to each other And the valve member is such that when one inlet is open, the valve member at the open inlet pushes the other valve member to a more closed position so that only one of the inlets is open. An apparatus, characterized in that the propellant, which does not contain any of the desired substance, is able to wash away any suspension or solution remaining in the filling head when the inlet for the propellant alone is open. 4. A filling head for filling a container under pressure with a suspension or solution in which a desired substance is suspended or dissolved in a propellant, which is in communication with the container during use. And a first and second inlet each in communication with the outlet via a common passage, and a spherical valve member, wherein the propellant containing the desired substance and The propellant free of the desired substance is introduced during use through each of the inlets, respectively, and the spherical valve member is adapted to prevent the fluid entering one of the inlets from flowing out of the other. A filling head for selectively and alternatively closing a second passage. 5. A filling head for filling a container under pressure with a suspension or solution in which a desired substance is suspended or dissolved in a propellant, which is in communication with the container during use. And a first and second inlet each communicating with the outlet via a common passage, wherein the inlets face each other and include the propellant containing the desired substance. And a propellant free of the desired substance is introduced through any of the inlets during use, respectively.
Further, the first and second inlets have valve members for opening and closing the respective inlets, wherein the respective valve members are adjacent to each other and the valve members are such that only one of the inlets is open. Filling valve, characterized in that when one inlet is open, the valve member at the open inlet pushes the other valve member to a more closed position. 6. A method for filling a container with a suspension or solution in which a drug is suspended or dissolved in a propellant under pressure, wherein the filling head according to claim 4 or 5 is filled in the container. A step of introducing a fixed amount of the suspension or solution into the container via the filling head; and Introducing a high-pressure propellant into the filling head and flushing the suspension or solution remaining in the filling head; and withdrawing the filling head from the container, wherein the suspension or solution is Circulating in a system including a filling head, wherein the filling head is capable of only filling at any one time either the suspension or solution or the propellant without the agent alone And wherein the method. 7. The method according to claim 6, wherein the propellant containing the drug and the propellant containing no drug are the same. 8. The method according to claim 6, wherein the propellant is 1,1,1,2 tetrafluoroethane. 9. The method according to claim 6, wherein the drug is salbutamol. 10. The method according to claim 6, wherein the drug is beclomethasone dipropionate.