JP2002532347A - dispenser - Google Patents

Abstract

(57) Abstract: An aerosol dispenser provided with a body (1) and means (7) sealed to the body (1) for dispensing substances from inside the dispenser. A closure (2), wherein the closure (2) is welded to the body (1) by laser welding between metals. The method of assembling an aerosol dispenser includes a metal body (1) and a metal closure (2) provided with a means (7) for dispensing a substance from inside the dispenser. The method of assembling an aerosol dispenser, wherein the closure (2) is laser welded (18) to the body (1) so as to form an intermetallic seal. To provide.

Description

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an aerosol (aerosol) dispenser, ie a dispenser from which a substance can be dispensed (administered) in the form of an aerosol. It particularly (but not exclusively) relates to aerosols of metered doses of the drug, for example metered doses of inhalation.

The top of a known dispenser is shown in vertical section in FIG. 1 of the accompanying drawings.
It has a metal can-shaped body (main body) 1 and a metal closure 2, and the closure 2 has a flange 3 whose lower end is crimped around an upper wall 4 of the can-shaped body 1. ing. The closure 2 has an annular passage 5 opening downward and receiving a sealing gasket 6 therein. The upper edge of the wall portion 4 of the can-shaped body 1 is in a state of being tightly fitted with the gasket 6.

The dispenser is provided with a valve device 7. The valve device 7
The purpose of this is to dispense a metered dose of the substance held in the can body 1 under pressure (
Administration). Most of the details are irrelevant to the present invention, and further, they are general. For the present discussion, it is mentioned that the valve arrangement 7 comprises a metering chamber 8 in which the dose before dispensing is held and a hollow stem 9 movable axially with respect to this chamber 8. That is enough. The stem 9 has a transfer port 10 and an outlet 11. When the stem is depressed from the position shown, a dose passes from chamber 8 through port 10 into the stem and out there through outlet 11. The stem 9 is slidably and sealingly fitted into an opening formed in the center of the seal ring 12.

[0004] French Patent Application No. 2543923 describes an aerosol dispenser similar to that described with reference to FIG. The dispenser
A fuselage having a dome-shaped upper portion welded to the main body portion and a valve retaining closure crimped in a conventional manner to the upper edge of the dome. Although not shown in detail, a gasket must be interposed in the crimping fastener to ensure a sufficient seal between the closure and the dome.

[0005] The material used for the gasket in the aerosol dispenser is carefully chosen to be as inert as possible when required for medical use, but nevertheless nevertheless to be dispensed It has been recognized that it is desirable to reduce the amount of gasket material that can be contacted. The largest gasket area in FIG. 1 is represented by the gasket 6, and it would therefore be particularly preferred to remove the gasket 6. Such elimination also potentially offers the potential of a cheaper dispenser than that shown in FIG. 1, due to the fact that one component can be reduced.

[0006] It is also desirable that the aerosol dispenser be as leakproof as possible. In particular, it is desirable to prevent the leakage of moisture into the container, which may interfere with the integrity of any aerosol formulation contained within the container. In that regard, the gasket 6 has been found to perform well in practice, but provides a potential leakage path extending circumferentially around the container. For this reason, it may be desirable to omit the gasket and provide a seal between the conductor 1 and the closure 2 that does not provide such a potential leakage path.

In accordance with one aspect of the present invention, there is provided an aerosol dispenser comprising: a fuselage; and a closure sealed to the fuselage and provided with means for dispensing a substance from within the dispenser. Wherein the closure is welded to the body by laser to metal welding.

[0008] Preferably, the intermetallic laser welding is performed between annular flanges on the body and the closure extending circumferentially around the axis of the body and the closure.

In one aspect, the flange is outwardly oriented and flat.

[0010] In another aspect, the flange is axially oriented and cylindrical.

Preferably, the flanges are welded, rolled and crimped.

Preferably, one of said flanges is wider than the other, and the outer edge of the wider flange is U-shaped such that the outer edge of the narrower flange is located inside,
The outer edges of both flanges extend substantially parallel to the wall of the adjacent fuselage.

In one aspect, the body is provided with a valve device. In another aspect, the closure is provided with a valve device.

According to another aspect of the present invention, there is provided a method of assembling an aerosol dispenser, comprising: a metal body; and a metal closure provided with a means for dispensing a substance from inside the dispenser. A method for assembling an aerosol dispenser, the method comprising: laser welding the closure to the body to form a metal-to-metal seal.

[0015] Preferably, the closure with an annular flange extending circumferentially around its own axis comprises a double flange at the open end of the fuselage with a complementary annular flange extending circumferentially around its own axis. Are coaxially positioned so that they contact each other in parallel.

Preferably, the flanges are illuminated and moved circumferentially along the flanges until they have completely circulated around the axis of the closure and the body, so that a substantially continuous space between the flanges The flanges are welded together by a laser beam that creates a weld.

In one aspect, the flange is outwardly oriented and flat.

Preferably, after the flanges are welded to each other, the flanges are bent so as to be oriented substantially in the axial direction.

In another aspect, the flange is axially oriented and cylindrical.

Preferably, one of the flanges is wider than the other, and after these flanges are welded together, the wider flange is rolled around the narrower flange and crimped. .

Preferably, the flanges are rolled and crimped after being welded together.

Preferably, the laser welding has a maximum average power of 10 W to 200 W and 1 kW
Implemented by a laser source with a maximum peak power of 〜１０10 kW. More preferably, the laser source has a pulse width of 0.5 to 20 microseconds and a pulse width of 10 to 1 microsecond.
With a maximum pulse energy of 00 joules.

According to another aspect of the present invention there is provided an aerosol dispenser as described above, filled with an aerosol suspension.

The aerosol suspension preferably contains a drug and a propellant.

The drug is preferably selected from the group consisting of albuterol, salmeterol, fluticasone propionate and beclomethasone dipropionate, and salts or solvates thereof, and any mixtures thereof.

The propellants are HFA-134a (1,1,1,2-tetrafluoroethane) and HFA-134a (1,1,1,2-tetrafluoroethane), which have been developed to replace conventional propellants which are thought to contribute to ozone depletion in the atmosphere. It is preferable to use an alternative propellant such as HFA-227 (1,1,1,2,3,3,3-heptafluoropropane) as a base.

Further features of the present invention will become apparent from the following description and accompanying drawings.

In FIG. 2, the same reference numerals are used for the corresponding parts as in FIG. At its upper end, the metal body 1 terminates in an outwardly facing flat annular flange 14, and the outer periphery of the metal closure 2 is also in the form of a flat annular flange 15. It turns out that it is making. These flanges 14, 15 are
The two members are laser-welded to each other along the mating surface 16 by metal-to-metal welding.
Laser welding allows a very localized limited heating to take place in the area of the weld itself. This can reduce the risk of improper heating of the medicament, thus allowing the can to be filled before the closure is securely attached to the can (alternatively, the valve The can can also be filled through the device).

The laser source can be any suitable for laser welding. Typically, the maximum average power is 10 W to 200 W, preferably 25 W to 100 W, and the maximum peak power is 10 kW to 1 kW, preferably 5 kW to 3 kW. The pulse width is typically 0.5 to 20 microseconds, and the maximum pulse energy is 1
It is from 00 to 10 joules, preferably from 50 to 25 joules.

The advantage of laser welding in the manufacture of a dispenser according to the invention lies in the precisely controllable low welding energy, which allows a precisely formed weld without affecting the rest of the dispenser. Becomes Laser welding can also be processed to be smooth and hermetically sealed. Furthermore, the laser power is generally very stable, so that consistent welding repeatability can be achieved.

Here, a procedure for forming a weld between the flanges 14 and 15 will be described with reference to FIG. As shown in FIG. 3, the laser source 17 is swirled until the laser beam 17 is completely circulated, with the laser beam 18 being directed circumferentially along the flange. In an alternative approach, the laser source 17 is fixedly mounted,
The container is rotated relative to the laser source 17 so that the laser beam 18 properly strikes the flanges 14,15.

When the flanges 14, 15 have the shape shown in FIG. 2, the contents of the dispenser under pressure exert a peeling force on the weld between the flanges. Despite the fact that the welded connection is strong enough to resist the forces that are reasonably exposed,
Relatively weak to peel force. However, if it is desired to avoid exposing the welded joint to the peeling force, the shape of the flange can be replaced by an axially oriented cylindrical shape as shown in FIG. To accomplish this, the flange may be welded to the shape shown in FIG. 2 and then bent 90 °, or the flange may be bent and then welded.

In the latter case, as shown in FIG. 4, the welded portion can be formed by inserting the ferrule 2 into the cylindrical body 1. Ferrule flange 15 aids insertion and positioning, and has a close fit (at least an intermediate fit) at the upper edge
It has been slightly spread out to help. The reason that such a fitting at the upper end between the two flanges 14 and 15 is required is that, whatever the gap between them, there is no need to hit the metal ends of the two flanges 14 and 15 and heat them. Rather, this would allow inappropriate laser beams to enter the fuselage 1.

The laser beam is directed to a peripheral joint between the body 1 and the ferrule 2. The body 1 and ferrule 2 assembly may be rotated with respect to the stationary laser beam, or, alternatively, the laser beam may be swiveled about the assembly. This welding is continued until the continuous welding of the periphery is completed.

FIG. 5 shows a modification of the flange shape of FIG. 4 as a method of avoiding the application of shear force to the welded joint. The flange shown in FIG. 5 is welded as shown in FIG. 2 and then bent downward.

A correctly performed laser weld should result in a perfect leak-tight seal between the flanges. However, as a precautionary measure, it is possible to further seal the flanges by providing the body and the closure with a U-shaped part that meshes with each other. This is shown in FIGS. 6 and 7a-7c. 7a to 7c show a continuous process for forming a structure shown in FIG. 6 by sealing a closure to a body. After the closure 2 and the fuselage 1 are formed and assembled together as shown in FIG. 7a, laser welding is carried out and then the rolling and crimping of FIGS. 7b and 7c.
) Work is performed.

FIGS. 1 to 7 c depict, in particular, embodiments in which the ferrule with a valve is weldable to a metal can body, but other variants are also possible. In particular, embodiments are envisaged in which the can body with valve can be welded to the bottom ferrule. The bottom ferrule may be dome-shaped or have an essentially flat shape.

The dispensers described herein are particularly suitable for dispensing (administering) drugs for the treatment of respiratory disorders. Thus, suitable agents may be selected, for example, from:

Analgesics such as, for example, codeine, dihydromorphine, ergotamine, fentanyl or morphine. For example, drugs for treating angina such as diltiazem. Anti-allergic agents such as cromogligic acid, ketotifen or nedocromil. Anti-infectives such as, for example, cephalosporins, penicillins, streptomycins, sulfonamides, tetracyclines and pentamidines. Antihistamines such as, for example, methapyrilene. Anti-inflammatory agents such as, for example, beclomethasone dipropionate, fluticasone propionate, flunisolide, budesonide, rofleponide, mometasone furonate or triamcinolone acetonide.

Antitussives, for example noscapine. For example, albuterol, salmeterol,
Ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pyrbuterol, leproterol, limiterol, terbutaline, isoethalin, tulobuterol or (-)-4-amino-3,5-dichloro-α-[[ Tracheal dilators such as [6- [2- (2-pyridinyl) ethoxy] hexyl] methyl] benzenemethanol.

Diuretics such as, for example, amiloride. Anticholinergic drugs such as ipratropium, tiotropium, atropine or oxitropium. Corticosteroids such as, for example, cortisone, hydrocortisone or blednisolone. Xanthine drugs such as aminophylline, choline theophyllate, lysine theophyllate or theophylline. Therapeutic proteins and peptides such as, for example, insulin or glucagon.

In order to optimize the activity and / or the stability of these agents, they are used in a suitable range in the form of a salt (for example, as an alkali metal or amine salt, or an acid addition salt). ), Or as an ester (eg, lower alkyl esters), or as a solvate (eg, hydrate).

Suitable agents include albuterol, salmeterol, fluticasone propionate and beclomethasone dipropionate, and salts or solvates thereof, for example, sulfated albuterol or xinafooxide of salmeterol (xi
nafoate).

A plurality of drugs can be supplied in combination. Suitable formulations containing active ingredient combinations include (eg, free base or sulfate) in combination with an anti-inflammatory steroid such as beclomethasone ester (eg, dipropionate oxide) or fluticasone ester (eg, propionate oxide). Salbutamol (as a salt) or salmeterol (as xinafoate).

It will be understood that the present disclosure is for illustrative purposes only and the invention extends to modifications, variations and improvements thereof.

The present application, of which the detailed description and claims are a part, may be used as a basis for priority in any subsequent application. The claims of such subsequent application may be directed to any feature or combination of features described herein. They can take the form of product, method or application claims and, by way of example, without limitation, a combination of one or more of the present application claims.

[Brief description of the drawings]

FIG. 1 is a vertical sectional view showing a conventional aerosol dispenser.

FIG. 2 is a vertical sectional view showing an embodiment of an aerosol dispenser according to the present invention.

FIG. 3 shows the embodiment of the invention shown in FIG. 2 together with parts of one form of a laser welding device (schematically shown).

FIG. 4 shows the embodiment of the invention shown in FIG. 2 together with a laser welding head (shown schematically).

FIG. 5 shows a modification of the embodiment shown in FIG. 4 in detail.

FIG. 6 is a diagram showing another embodiment of the present invention.

FIG. 7a illustrates a continuous assembly process of the embodiment shown in FIG. 6;

FIG. 7b shows a continuous assembly process of the embodiment shown in FIG. 6;

FIG. 7c is a diagram showing a continuous assembly process of the embodiment shown in FIG. 6;

[Procedural Amendment] Submission of translation of Article 34 Amendment

[Submission date] October 12, 2000 (2000.10.12)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Claims

[Correction method] Change

[Correction contents]

[Claims]

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0007

[Correction method] Change

[Correction contents]

In accordance with one aspect of the present invention, there is provided an aerosol dispenser for dispensing a medicament, comprising: a body and a seal sealed to the body for dispensing a substance from within the dispenser. A closure provided with a valve device, said closure being directly welded to said fuselage by metal-to-metal laser welding.

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] 0013

[Correction method] Deleted

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0014

[Correction method] Change

[Correction contents]

According to another aspect of the present invention, there is provided a method of assembling an aerosol dispenser for dispensing a medicament, comprising a metal body and a valve device for dispensing a substance from inside the dispenser. A method of assembling an aerosol dispenser including a metal closure provided with a laser closure, wherein the closure is directly laser welded to the body to form an intermetallic seal, An assembly method is provided.

──────────────────────────────────────────────────続 き Continuation of front page (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE ), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID , IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW (71 ) Applicant Glaxo Wellcome House, Berkeley Avenue Greenfield, Middlesex UB60NN, Great Britain in F term (reference) 3E014 PA01 PB01 PB08 PC02 PD01 PF10

Claims (22)

[Claims] An aerosol dispenser, comprising: a body (1); and a closure sealed to the body (1) and provided with means (7) for dispensing a substance from inside the dispenser. (2) The aerosol dispenser, wherein the closure (2) is welded to the body (1) by laser welding between metals. 2. The metal-to-metal connection between annular flanges (14, 15) on the body (1) and the closure (2) extending circumferentially around the axis of the body (1) and the closure (2). The aerosol dispenser according to claim 1, wherein laser welding is performed. 3. The aerosol dispenser according to claim 2, wherein the flanges (14, 15) are directed outwardly and are flat. 4. The flange (14, 15) is axially oriented and cylindrical.
An aerosol dispenser according to claim 2, characterized in that: 5. An aerosol dispenser according to claim 2, wherein the flanges (14, 15) are welded, pressed and crimped. 6. One of said flanges (15) is wider than the other (14), and the outer edge of the wider flange (15) has the outer edge of the narrower flange (14) inside. 5. The U-shape of claim 2, wherein the outer edges of both flanges extend substantially parallel to the wall of the adjacent fuselage (1). Aerosol described
dispenser. 7. An aerosol dispenser according to claim 1, wherein the body (1) is provided with a valve device (7). 8. An aerosol dispenser according to claim 1, wherein the closure (2) is provided with a valve device (7). 9. A method of assembling an aerosol dispenser, comprising: a metal body (1); and a metal closure (2) provided with means (7) for dispensing a substance from inside the dispenser. A method for assembling an aerosol dispenser, comprising: welding the closure (2) to the body (1) by laser so as to form a metal-to-metal seal. 10. The fuselage (2) with an annular flange (15) extending circumferentially about its own axis, the body comprising a complementary annular flange (14) extending circumferentially about its own axis. 10. The method according to claim 9, wherein the flanges (14, 15) are coaxially positioned at the open end of (1) so as to contact each other in parallel. 11. Irradiation on the flanges (14, 15) and movement in the circumferential direction along the flanges (14, 15) until complete rotation around the axis of the closure (2) and the body (1) is completed. The laser beam (17) produces a substantially continuous weld between the flanges (14, 15).
4. The aerosol according to claim 10, wherein (4, 15) are welded to each other.
Dispenser assembly method. 12. The method according to claim 11, wherein the flanges (14, 15) are directed outwardly and are flat. 13. The method for assembling an aerosol dispenser according to claim 12, wherein the flanges (14, 15) are welded to each other and then bent so as to be oriented substantially in the axial direction. . 14. The flange (14, 15) is axially oriented and cylindrical.
The method for assembling an aerosol dispenser according to claim 11, wherein: 15. One of said flanges (15) is wider than the other (14), and after these flanges (14, 15) are welded together, the wider flange (15) is narrower. A method according to any of claims 10 to 14, characterized in that it is pressed and crimped around one of the flanges (14). 16. The method for assembling an aerosol dispenser according to claim 10, wherein the flanges (14, 15) are welded to each other, then pressed and crimped. . 17. The laser welding method according to claim 10, wherein the laser welding is performed by a laser source having a maximum average power of 10 W to 200 W and a maximum peak power of 1 kW to 10 kW. A method for assembling the described aerosol dispenser. 18. The aerosol dispenser of claim 17, wherein said laser source has a pulse width of 0.5 to 20 microseconds and a maximum pulse energy of 10 to 100 Joules. 19. The aerosol dispenser according to claim 1, wherein the dispenser is filled with an aerosol suspension. 20. The aerosol dispenser according to claim 19, wherein said aerosol suspension contains a drug and a propellant. 21. The drug of claim 20, wherein the drug is selected from the group consisting of albuterol, salmeterol, fluticasone propionate and beclomethasone dipropionate, and salts or solvates thereof, and any mixtures thereof. An aerosol dispenser as described. 22. The propellant, wherein the propellant is selected from the group consisting of 1,1,1,2-tetrafluoroethane and 1,1,1,2,3,3,3-heptafluoropropane. Claim 20 or 2
An aerosol dispenser according to claim 1.