Abstract:
A medicament dispenser including a housing, a medicament container having a dispensing outlet; an agitator for agitating the contents; and a driver for driving the agitator independent of any container movement. The driver includes an energy storeage for storing energy releasable to drive the agitator. The medicament container may be a metered dose inhaler or delivering a suitable inhalable medicament.

Description:
The instant application is filed under 35 U.S.C. § 371 as the United States National Phase Application of International Application No. PCT/EP00/09640 filed 28 Sep. 2000 claiming priority from GB 9924780.1 filed 21 Oct. 1999. 
     TECHNICAL FIELD 
     This invention relates to a medicament dispenser comprising a housing and a medicament container. The dispenser includes an agitator for agitating the medicament container by release of stored energy. The dispenser is particularly suitable for use as an inhalation device. 
     BACKGROUND TO THE INVENTION 
     Known medicament dispensers comprise a medicament container having a dispensing outlet for dispensing of the medicament therefrom. Such medicament dispensers often require the patient to agitate the contents thereof prior to dispensing to ensure ready and uniform dispensing of the medicament. The agitation involves a manual shaking action. 
     Agitation is particularly required where the dispenser comprises medicament as a suspension in a propellant formulation. A well-known example of this type is the metered dose inhaler for dispensing of respiratory medicament which comprises an aerosol container having a dispensing valve. The medicament is comprised within the aerosol container in the form of a suspension comprising propellant and optionally other additives such as solvents or surfactants. Such suspensions have a tendency to settle out, sediment or cream. A pre-dispensing agitation step is necessary to re-establish a uniform suspension so that uniform dispensing of medicament may be achieved. 
     Agitation can also be required where the medicament is in powder form. It is well known that powders can tend to settle out, agglomerate or even cake on storage. The agitation therefore performs the function of breaking up any agglomerates or cakes that may have formed, and thereby ensures that the powder is readily dispensable. 
     Various suggestions have been made to enhance the manual shaking action to maximise the effect of agitation. 
     PCT Patent Application No. WO95/30607 describes a metered dose dispensing valve including a movable agitator in the metering chamber. Manual shaking of the valve causes movement of the agitator therein which is stated to assist mixing of the drug suspension in the metering chamber. 
     PCT Patent Application No. WO96/08284 describes an inhalation device for dispensing powder form medicament including a movable weight which is configured to strike an anvil upon manual shaking of the device. The striking action causes a jolt which acts such as to assist transfer of the powder from a reservoir container to a metering recess formed in a dosing member. 
     Whilst manual shaking is a generally effective means for providing agitation it is sometimes inconvenient for the patient. In social situations, the patient often wishes to administer their medicament discretely and without drawing attention to themselves. Manual shaking of the dispenser is difficult to perform in a discrete fashion. This can lead to patient embarrassment. There is also always the possibility that the patient forgets to shake the dispenser, or does so inadequately, thereby affecting the medicament dose deliverable. 
     The Applicants have now developed a medicament dispenser which requires little or no manual shaking. The dispenser comprises a medicament container within a housing. The dispenser includes an agitator for agitating the medicament container and a driver for driving the agitator. The driver comprises an energy store for storing energy which energy is releasable to drive the agitator. The dispenser therefore provides for agitation of the medicament container and contents thereof without requiring shaking by the patient. 
     SUMMARY OF INVENTION 
     According to one aspect of the present invention there is provided a medicament dispenser comprising a housing; a medicament container having a dispensing outlet; an agitator for agitating said container; and a driver for driving said agitator, wherein said driver comprises an energy store for storing energy which energy is releasable to drive the agitator. 
     Preferably, the container is mounted for movement within the housing. 
     In one aspect, the container is rotatable within the housing. 
     In another aspect, the container is movable in a reciprocating fashion within the housing. 
     Preferably, the agitator couples mechanically to the container. 
     In one aspect, the agitator couples to the container through a cam arrangement. The cam arrangement may comprise a stepped cam or a snail cam. 
     In another aspect, the agitator couples to the container through a con-rod and crank arrangement. 
     In a further aspect, the agitator couples to the container through a gear drive arrangement. 
     In a further aspect, the agitator couples magnetically to the container. Preferably, either or both of the agitator or the container comprises magnetic material or material which is magnetically inductive, that is to say material into which magnetism can be induced. The material may be permanently or non-permanently magnetisable. 
     In a further aspect, the agitator couples pneumatically to the container. 
     In a further aspect, the agitator couples hydraulically to the container. 
     In a further aspect, the agitator comprises a multi-component strip or wire which is deformable in response to electrical current flow. 
     Suitable multi-component strips typically comprise a plurality of layers of material, each material having a different coefficient of thermal expansion. Preferred examples of multi-component strips include strips comprising multiple layers of different metals (e.g. bimetallic strips) and strips comprising at least one piezoelectric or piezoresistive material. Suitable piezoelectric materials include piezoelectric ceramics, such as compounds of lead zirconate and lead titanate, and piezoelectric crystals which are generally polycrystalline ferroelectric materials with the perovskite structure. 
     Suitable multi-component wires typically comprise alloys of two or more metals wherein one or more of the metals undergoes a temperature induced phase change in response to electrical current flow. Preferred examples of multi-component wires include those comprised of alloys of titanium and nickel which contract when electric current is applied. 
     Preferably, the agitator provides wave energy to the container. More preferably, the agitator is an acoustic wave energy generator or a resonant wave energy generator. 
     Preferably, the container comprises a guide to guide fluid flow within the container. More preferably, the guide comprises a vane arrangement or a movable impeller. 
     Preferably, the dispenser comprises a stop mechanism for stopping movement of the container. More preferably, the stop mechanism is capable of providing a shock stop to the container. 
     Preferably, the energy store comprises a biasable resilient member. More preferably, the biasable resilient member is a spring. 
     Preferably, the energy store comprises a clockwork mechanism. 
     Preferably, the energy store comprises a battery. 
     Preferably, the driver is responsive to a patient-actuable trigger. More preferably, the trigger comprises a button, switch or lever arrangement. Most preferably, the trigger comprises a sensor which senses the breath of a patient. 
     In one aspect, the sensor comprises a breath-movable element which is movable in response to the breath of a patient. More preferably, the breath-movable element is selected from the group consisting of a vane, a sail, a piston and an impeller. 
     In another aspect, the sensor comprises a pressure sensor for sensing the pressure profile associated with the breath of a patient. 
     In a further aspect, the sensor comprises an airflow sensor for sensing the airflow profile associated with the breath of a patient. 
     In a further aspect, the sensor comprises a temperature sensor for sensing the temperature profile associated with the breath of a patient. 
     In a further aspect, the sensor comprises a moisture sensor for sensing the moisture profile associated with the breath of a patient. 
     In a further aspect, the sensor comprises a gas sensor for sensing the oxygen or carbon dioxide profile associated with the breath of a patient. 
     Preferably, dispensing from the dispensing outlet is responsive to a second patient-actuable trigger. 
     Preferably, the patient-actuable triggers are coupled such that agitation and dispensing occurs in a sequential fashion. 
     In one aspect, the container is an aerosol container. Preferably, the container comprises a metering valve at the dispensing outlet. 
     Preferably, the aerosol container comprises a suspension of a medicament in a propellant. More preferably, the propellant comprises liquefied HFA134a, HFA-227 or carbon dioxide. The medicament can be selected from the group consisting of albuterol, salmeterol, fluticasone propionate, beclomethasone dipropionate, salts or solvates thereof and any mixtures thereof. 
     In another aspect, the aerosol container comprises a compressed gas, preferably compressed air. 
    
    
     
       BRIEF DESCRIPTION OF THE INVENTION 
       The invention will now be described further with reference to the accompanying drawings in which: 
         FIGS. 1   a  and  1   b  show sectional views of a first medicament dispenser in accord with the present invention; 
         FIGS. 2   a  and  2   b  show sectional views of a second medicament dispenser in accord with the present invention; 
         FIGS. 3   a  and  3   b  show sectional views of a third medicament dispenser in accord with the present invention; 
         FIGS. 4   a  and  4   b  show sectional views of a fourth medicament dispenser in accord with the present invention; and 
         FIG. 4   c  shows a perspective cutaway view of a detail of the medicament dispenser of  FIGS. 4   a  and  4   b.    
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       FIGS. 1   a  and  1   b  show a medicament dispenser mounted within an actuator housing  20 . The actuator housing  20  is shown in the form of a laboratory test rig. It will be appreciated that the test rig can be adapted by way of workshop modifications to form a more recognizable product housing (e.g. an inhaler device product housing) incorporating the same functional elements.  FIG. 1   b  shows a sectional view of the dispenser and housing  20  taken along section B—B of  FIG. 1   a.    
     The medicament dispenser is suitable for use in a metered dose inhaler (MDI) for delivery of inhalable medicament. The dispenser comprises an aerosol can  10  having a dispenser outlet in the form of a metering valve  12 . The valve gasket  14  is fixedly attached (typically by crimping) to the aerosol can body  10 . The can suitably comprises a suspension of medicament in a propellant. 
     The can  10  is mounted within a cradle comprising fixed uprights  22 ,  24  and base section  26  which has a central aperture for receipt of the neck of the can such that the can  10  sits therein. The base section  26  is freely movable up and down on the uprights  22 ,  24 . The base of the can  10  is provided with an acetal pad  16  which receives compression spring  30 . The compression spring  30  connects with pre-load adjuster  32  which is itself fixed to the housing  20 . Overall, it may thus be appreciated that the can  10  is mounted within the housing  20  such that it is movable up and down but is under the influence of a generally downward spring bias. 
     The base section  26  of the can-receiving cradle is also provided with a cam follower  28  which follows snail cam  40 . Snail cam  40  is itself axially mounted to the housing  20  and is drivable by the action of torsion spring drive  42 . In other embodiments, the torsion spring drive  42  may be replaced by another suitable source of drive energy such as a clockwork or battery-driven electric motor. 
     Agitation of the aerosol can  10  is achievable by the following steps. The torsion spring drive  42  is actuated to drivably rotate the snail cam  40 . The cam follower  28  follows the path defined by the snail cam  40  such that the base section  26  and can  10  sitting therein are initially moved gradually upwards but then suddenly released downwards. The can  10  is thus submitted to a shock downward movement which agitates the contents thereof. 
       FIGS. 2   a  and  2   b  show a medicament dispenser herein mounted within an actuator housing  120 . The actuator housing  120  is shown in the form of a laboratory test rig. It will be appreciated that the test rig can be adapted by way of workshop modifications to form a more recognisable product housing incorporating the same functional elements.  FIG. 2   b  shows a sectional view of the dispenser and housing  120  taken along section B—B of  FIG. 2   a.    
     The medicament dispenser is suitable for use in a metered dose inhaler (MDI) for delivery of inhalable medicament. The dispenser comprises an aerosol can  110  having a dispenser outlet in the form of a metering valve  112 . The valve gasket  114  is fixedly attached (typically by crimping) to the aerosol can body  110 . The can suitably comprises a suspension of medicament in a propellant. 
     The can  110  is mounted within a cradle comprising fixed uprights  122 ,  124  and base section  126  which has a central aperture for receipt of the neck of the can such that the can  110  sits therein. The base section  126  is freely movable up and down on the uprights  122 ,  124 . In other embodiments, the can  110  may be biased in a generally downward direction, for example by a compression spring arrangement as shown in  FIGS. 1   a  and  1   b.    
     The base section  126  of the can-receiving cradle is also provided with a cam follower  128  which follows stepped cam  140 . A suitable stepped cam has 9 steps per 360 degree ° and 0.45 mm drop per step. The stepped cam  140  is itself axially mounted to the housing  120  and is drivable by the action of torsion spring drive  142 . In other embodiments, the torsion spring drive  142  may be replaced by another suitable drive motor such as a clockwork or electric motor. 
     Agitation of the aerosol can  110  is achievable by the following steps. The torsion spring drive  142  is actuated to drivably rotate the stepped cam  140 . The cam follower  128  follows the path defined by the stepped cam  140 . The base section  126  and can  110  sitting therein thus follow stepped movements comprising a gradually upward movement and more sudden downwards release. The can  110  is thus submitted to regularly stepped downward shock movements which agitate the contents thereof. 
       FIGS. 3   a  and  3   b  show a medicament dispenser herein mounted within an actuator housing  220 . The actuator housing  220  is shown in the form of a laboratory test rig. It will be appreciated that the test rig can be adapted by way of workshop modifications to form a more recognizable product housing incorporating the same functional elements.  FIG. 3   b  shows a sectional view of the dispenser and housing  220  taken along section B—B of  FIG. 3   a.    
     The medicament dispenser is suitable for use in a metered dose inhaler (MDI) for delivery of inhalable medicament. The dispenser comprises an aerosol can  210  having a dispenser outlet in the form of a metering valve  212 . The valve gasket  214  is fixedly attached (typically by crimping) to the aerosol can body  210 . The can suitably comprises a suspension of medicament in a propellant. 
     The can  210  is mounted within cradle  226  which has a central aperture for receipt of the neck of the can such that the can  210  sits therein. The cradle  226  is movably mounted to the housing  220  through axle  228 . The axle  228  connects with con-rod  241  which in-turn connects with crank  240 . The crank  240  is axially mounted to the housing  220  and is drivable by the action of torsion spring drive  242 . Overall, it may be appreciated that cradle  226  and can  210  are movable in a reciprocating (i.e. rocking) movement on axle  228  responsive to movement of the con-rod  241  and crank  240  arrangement. Drive energy is provided by the torsion spring  242 . In other embodiments, the torsion spring drive  242  may be replaced by another suitable drive motor such as a clockwork or electric motor. 
     Agitation of the aerosol can  210  is achievable by the following steps. The torsion spring drive  242  is actuated to drivably rotate the crank  240  and con-rod  241 . The movement of con-rod  241  in turn results in a rocking movement of the cradle  226  and can  220  on axle  228 . The rocking movement agitates the can  210  and contents thereof. 
       FIGS. 4   a  and  4   b  show a medicament dispenser herein mounted within an actuator housing  320 . The actuator housing  320  is shown in the form of a laboratory test rig. It will be appreciated that the test rig can be adapted by way of workshop modifications to form a more recognizable product housing incorporating the same functional elements.  FIG. 4   b  shows a sectional view of the dispenser and housing  320  taken along section B—B of  FIG. 4   a.    
     The medicament dispenser is suitable for use in a metered dose inhaler (MDI) for delivery of inhalable medicament. The dispenser comprises an aerosol can  310  having a dispenser outlet in the form of a metering valve  312 . The valve gasket  314  is fixedly attached (typically by crimping) to the aerosol can body  310 . The can suitably comprises a suspension of medicament in a propellant. 
       FIG. 4   c  shows a perspective cutaway view of a detail of the aerosol can of  FIGS. 4   a  and  4   b . The interior of the can may be seen to be provided with plural vanes forming a vane arrangement  316 . The vane arrangement  316  acts such as to guide the flow of the fluid contents of the aerosol can  310 . 
     The can  310  is mounted within horizontal support  326  which has a central aperture for receipt of the neck of the can such that the can  310  sits freely therein. The horizontal support  326  is fixed to the housing  320 . Sleeve  350  is fixed to the exterior of the valve gasket  314  of can  310 . The sleeve  350  is provided with bevelled lip  352  which connects with gear drive wheel  340  which is axially mounted to the housing  320 . The gear drive wheel  340  is itself rotationally drivable by torsion spring drive  342 . In other embodiments the torsion spring drive  342  may be replaced by any suitable drive motor. 
     Agitation of the aerosol can  310  is achievable by the following steps. The torsion spring drive  342  is actuated to drive the gear drive wheel  340 . The gear drive wheel  340  drives rotation of the sleeve  350  and hence of the aerosol can  310 . The rotation of the can  310  agitates the contents thereof assisted by the presence of the vane arrangement  316  within the can  310 . 
     It may be appreciated that the torsion spring drive arrangement shown in the preceding figures may be implemented in an inhaler device such that torsion energy is provided thereto by a defined user movement. The movement could for example, be provided by a push button action. In an alternative, the device may be provided with a pivoted cover for a mouthpiece wherein the opening of the cover results in torsion energy being provided to the spring. 
     It may be appreciated that any of the parts of the dispenser which contact the medicament suspension may be coated with materials such as fluoropolymer materials which reduce the tendency of medicament to adhere thereto. Any movable parts may also have coatings applied thereto which enhance their desired movement characteristics. Frictional coatings may therefore be applied to enhance frictional contact and lubricants used to reduce frictional contact as necessary. 
     The medicament dispenser of the invention is suitable for dispensing medicament, particularly for the treatment of respiratory disorders such as asthma and chronic obstructive pulmonary disease. Appropriate medicaments may thus be selected from, for example, analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations, e.g., diltiazem; antiallergics, e.g., cromoglycate (e.g. s the sodium salt), ketotifen or nedocromil (e.g. as the sodium salt); antiinfectives e.g., cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine; antihistamines, e.g., methapyrilene; anti-inflammatories, e.g., beclomethasone (e.g. as the dipropionate ester), fluticasone (e.g. as the propionate ester), flunisolide, budesonide, rofleponide, mometasone e.g. as the furoate ester), ciclesonide, triamcinolone (e.g. as the acetonide) or 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioic acid S-(2-oxo-tetrahydro-furan-3-yl) ester; antitussives, e.g., noscapine; bronchodilators, e.g., albuterol (e.g. as free base or sulphate), salmeterol (e.g. as xinafoate), ephedrine, adrenaline, fenoterol (e.g. as hydrobromide), formoterol (e.g. as fumarate), isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (e.g. as acetate), reproterol (e.g. as hydrochloride), rimiterol, terbutaline (e.g. as sulphate), isoetharine, tulobuterol or 4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)-benzothiazolone; adenosine  2   a  agonists, e.g. 2R,3R,4S,5R)-2-[6-Amino-2-(1S-hydroxymethyl-2-phenyl-ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol (e.g. as maleate); α4 integrin inhibitors e.g. (2S)-3-[4-({[4-(aminocarbonyl)-1-piperidinyl]carbonyl}oxy)phenyl]-2-[((2S)-4-methyl-2{[2-(2-methylphenoxy)acetyl]amino}pentanoyl)amino]propanoic acid (e.g. as free acid or potassium salt), diuretics, e.g., amiloride; anticholinergics, e.g., ipratropium (e.g. as bromide), tiotropium, atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone or prednisolone; xanthines, e.g., aminophylline, choline theophyllinate, lysine theophyllinate or theophylline; therapeutic proteins and peptides, e.g., insulin or glucagon; vaccines, diagnostics and gene therapies. It will be clear to a person skilled in the art that, where appropriate, the medicaments may be used in the form of salts, (e.g., as alkali metal or amine salts or as acid addition salts) or as esters (e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimise the activity and/or stability of the medicament and/or to minimise the solubility of the medicament in the propellant. Preferred medicaments are selected from albuterol, salmeterol, fluticasone propionate and beclomethasone dipropionate and salts or solvates thereof, e.g., the sulphate of albuterol and the xinafoate of salmeterol. 
     Medicaments can also be delivered in combinations. Preferred formulations containing combinations of active ingredients contain salbutamol (e.g., as the free base or the sulphate salt) or salmeterol (e.g., as the xinafoate salt) or formoterol (e.g. as the fumarate salt) in combination with an antiinflammatory steroid such as a beclomethasone ester (e.g., the dipropionate) or a fluticasone ester (e.g., the propionate) or budesonide. A particularly preferred combination is a combination of fluticasone propionate and salmeterol, or a salt thereof (particularly the xinafoate salt). A further combination of particular interest is budesonide and formoterol (e.g. as the fumarate salt). 
     It will be understood that the present disclosure is for the purpose of illustration only and the invention extends to modifications, variations and improvements thereto. 
     The application of which this description and claims form part may be used as a basis for priority in respect of any subsequent application. The claims of such subsequent application may be directed to any feature or combination of features described therein. They may take the form of product, method or use claims and may include by way of example and without limitation, one or more of the following claims: