UNIT FOR THE MICRONIZATION AND DOSAGE OF SOLID ACTIVE AGENTS

Abstract

The invention relates to a unit for the micronization of a solid active agent, such as a salt, preferably table salt (NaCI), for inhalation, comprising a micronizer driven by a motor. The unit according to the invention is characterised in that micronization is performed by a unit constituted by a closed rotary drum (2) receiving a solid active agent having the same grain size, preferably 0.1-4 mm, as table salt (NaCI), where the wall surfaces of the micronizer unit are made at least in part of a material having a filtering capacity of 0.1-1000 m, the material preferably being a mesh-like or microperforated material. A further unit according to the invention is characterised in that the micronizer consists of a rotary block (23) made of the active agent, a friction block (24) adapted to be in frictioning relation with the rotary block, and a clamping mechanism (25) adapted for holding the friction block (24) in position and for clamping the friction block (24) to the rotary block (23), the micronizer being disposed in a closed housing (11), and the wall surfaces of the housing (11) being at least in part made of a material having a filtering capacity of 0.1-1000 m.

Claims

1. Unit (1) for micronization of a solid active agent to be micronized for inhalation purposes, comprising a micronizer driven by a motor (3), characterised in that micronization is performed by a unit constituted by a closed rotary drum (2) containing a solid active agent having the same grain size as table salt (NaCl), the rotary drum having wall surfaces made at least in part of a material having a filtering capacity of 0.1-1000 m.

2-18. (canceled)

19. The unit according to claim 1 wherein the solid active agent is table salt (NaCl).

20. The unit according to claim 1, characterised in that at least a portion of the wall surfaces of the rotary drum (2) is made of a material having a filtering capacity of 0.1-100 m.

21. The unit according to claim 1, characterised in that at least a portion of the wall surfaces of the rotary drum (2) is made of a material having a filtering capacity of 0.1-20 m.

22. The unit (1) according to claim 1, characterised in that the rotary drum (2) is driven by a constant rotational speed motor (3), the longitudinal axis of the rotary drum (2) being set at an angle not exceeding 75 with respect to the horizontal.)

23. The unit (1) according to claim 1, characterised in that the rotary drum (2) is spun up by the motor (3) in a cyclical manner, the rotary drum (2), having a diameter of 3.1 cm, and being half filled-up, the resting rotary drum (2) undergoing an accelerating rotary motion with an angular acceleration of 25 revolutions/s.sup.2.

24. The unit according to claim 1, characterised in that a heating element (7) is included under the rotary drum (2) or in the air path upstream of the rotary drum (2).

25. Unit (1) for the micronization for inhalation purposes of a solid active agent comprising a micronizer driven by a motor, characterised in that the micronizer consists essentially of a rotary block (23) made of an active agent material, a friction block (24) adapted to be in friction relationship with the rotary block (23), the friction block (24) being made of active agent material to be micronized for inhalation purposes, and a clamping mechanism (25) adapted for holding the friction block (24) in position and for clamping the friction block (24) to the rotary block (23).

26. The unit according to claim 25 wherein the solid active agent is table salt (NaCl).

27. The unit (1) according to claim 25, characterised in that the rotary block (23) has a disc or ring shape.

28. The unit (1) according to claim 25, characterised in that the rotary block (23) and the friction block (24) are made of the same material.

29. The unit (1) according to claim 25, characterised in that the unit is enclosed in a housing (11) whose air input and output portions are covered by a material having a filtering capacity of 0.1-1000 m.

30. The unit according to claim 25, characterised in that a heating element (7) is disposed under the rotary block (23).)

31. The unit according to claim 1, characterised in that the unit is disposed in an accumulation and dosing chamber (8) fitted with flap valves (9) and/or mechanical or electric blocking valves (10).

32. The unit according to claim 25, characterised in that the unit is disposed in an accumulation and dosing chamber (8) fitted with flap valves (9) and/or mechanical or electric blocking valves (10).)

33. The unit (1) according to claim 1, characterised in that the unit further comprises control electronics (13), the control unit (16) of the control electronics (13) being fitted with an electronic device adapted for blocking the operation of the unit based on parameter values specified in advance and the measured operating data.

34. The unit (1) according to claim 25, characterised in that the unit further comprises control electronics (13), the control unit (16) of the control electronics (13) being fitted with an electronic device adapted for blocking the operation of the unit based on parameter values specified in advance and the measured operating data.)

35. The unit (1) according to claim 1, further including a fan (4).

36. The unit (1) according to claim 25, further including a fan (4).)

37. The unit (1) according to claim 1, further including a housing and/or a nasal adapter or mouthpiece.

38. The unit (1) according to claim 25, further including a housing and/or a nasal adapter or mouthpiece.

39. Air treatment apparatus characterised in that the apparatus comprises a unit (1) according to claim 1 that is disposed in an air flow path.

40. Indirect inhaler apparatus characterised in that the apparatus comprises a unit (1) according to claim 1 that is disposed in an air flow path.

41. Direct inhalation apparatus characterised in that the apparatus comprises a unit (1) according to claim 1 that is disposed in the air flow path.

42. Air treatment apparatus characterized in that the apparatus comprises a unit (1) according to claim 25 that is disposed in an air flow path.

43. Indirect inhaler apparatus characterized in that the apparatus comprises a unit (1) according to claim 25 that is disposed in an air flow path.

44. Direct inhalation apparatus characterized in that the apparatus comprises a unit (1) according to claim 25 that is disposed in the air flow path.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Preferred embodiments of the unit according to the present invention will be described in detail below, referring to the attached drawings, where

[0043] FIG. 1 is the schematic drawing of the first preferred embodiment of the unit according to the invention,

[0044] FIG. 2 is the schematic drawing of the second preferred embodiment of the unit according to the invention,

[0045] FIG. 3 is an exemplary arrangement for building the unit according to the invention into an indirect inhaler device,

[0046] FIG. 4 is an exemplary arrangement for building the unit according to FIG. 2 into a direct inhaler device,

[0047] FIG. 5 shows the block diagram of an exemplary control unit of the unit according to the invention, and

[0048] FIG. 6 is the schematic drawing of a further preferred embodiment of the unit according to the invention that does not include a rotary drum.

MODES FOR CARRYING OUT THE INVENTION

[0049] The unit according to the invention, illustrated in FIG. 1, consists of two major parts, a rotary drum 2 and a motor 3. The cylindrical surface of the rotary drum 2 is at least in a part of its surface made of a material having a filtering capacity of 0.1-100 m, preferably a closely woven metal mesh or microperforated sheet. The drum is expediently formed as a cylinder with a surface having a filtering capacity of 0.1-1000 m, but it may also have a different, e.g. a spherical shape. The filter material has a typical filtering capacity of 0.1-20 microns, but the particle size required for therapy can be differentit may be as large as 100 microns for application primarily in the upper respiratory tract.

[0050] Since there is no officially established upper limit for the particle size of inhalable dust particles floating for a limited time (according to the WHO the particle size ranges from under 1 micron to above 100 microns, with no specific upper limit), the upper limit of the particle size range let through by the filter has been specified as 1000 microns, which allows an appropriate leeway. On the other hand, with regard to the fact that the presently applied method of micronization generates extremely fine particles, having even sub-micron particle size, thenwhile although the most expedient maximum particle size would be e.g. 0.1-20 microns but different maximum particle size values are not harmful eitherdriven, for example, by economical considerations, the use of materials having coarser filtering capacity may also be allowed, which results in an active agent with a particle size primarily appropriate for the application, and also in a micronized active agent having coarser particles that settle in the environment and in the upper respiratory tract. The filtering capacity range of 0.1-1000 m has been specified based on this.

[0051] The active agent grains having the same grain size as table salt (NaCl), typically 0.1-4 mm, are placed in the rotary drum 2 in such a manner that the material does not take up the entire volume of the rotary drum 2. During the operation of the unit, fine particles of the active agent separate from the grains loaded in the rotary drum 2. The unit 1 optionally includes a fan 4. In this exemplary embodiment the fan 4 and the rotary drum 2 have a common shaft 6 driven by a motor 3. Also, in this embodiment a reducing gear 5 is disposed between the motor 3 and the rotary drum 2. The reducing gear can also be omitted. It should be noted that the rotary drum 2 and the fan 4 may be driven independently of each other.

[0052] A heating element 7, adapted for keeping the active agent loaded in the rotary drum 2 sufficiently dry during operation, is disposed below the rotary drum 2.

[0053] It has to be noted that the heating element 7 may also be omitted.

[0054] Depending on the intended use, the unit 1 can be fitted with control electronics 13, the functionality whereof will be described in detail later.

[0055] FIG. 2 illustrates an embodiment of the unit 1 shown in FIG. 1 that also comprises an accumulation and dosing chamber 8 fitted with flap valves 9 and/or electromechanical or mechanical blocking valves 10 at its input and output sides. For the sake of simplicity, both solutions have been included herein. The accumulation and dosing chamber 8 according to FIG. 2 may at the same time be the housing of an inhaler device. The unit 1 may also be fitted with control electronics 13. The arrow 14 indicates the direction of the air flow through the accumulation and dosing chamber 8.

[0056] FIG. 3 shows another exemplary embodiment of the unit 1 illustrated in FIG. 1, a simple apparatus comprising a fan. The unit 1 according to the invention and the control electronics 13 thereof are disposed inside the housing 11 of the apparatus. Again, the arrow 14 indicates the direction of the air flow.

[0057] As it is seen in the drawing, in this embodiment there is no reducing gear between the rotary drum 2 and the fan 4, and thus the fan 4 and the rotary drum 2 are operating at the same rotational speed. The embodiment described above can be applied as a simple, tabletop indirect inhaler apparatus comprising a fan.

[0058] FIG. 4 illustrates another exemplary embodiment of the unit shown in FIG. 2.

[0059] In the unit 1, no reducing gear is disposed between the rotary drum 2 and the fan 4, and thereby the rotary drum 2 and the fan 4 are driven with the same rotational speed by the motor 3. The unit 1 is also equipped with control electronics 13. The unit 1 is implemented as a handheld device adapted for inhalation. A respective flap valve 9 is disposed at both ends of the housing 11 that receives the unit 1. By means of the flap valves 9 the prepared dose can be prevented from escaping from the housing before suction is applied to the adapter 12 connected to one end of the housing, and moisture can also be prevented from reentering the device through the adapter (which the users doing the inhalation place in their mouth).

[0060] It should be noted that the unit illustrated in FIGS. 1 and 2 can be built into any inhaler or air treatment device/apparatus, but it is imperative that the unit 1 is located in, or is connected to, the air flow path of the inhaler device/apparatus.

[0061] The rotary drum 2 of the unit 1 illustrated in FIGS. 1-4 operates either in a constant rotational speed mode or in a mode based on rapid rotational speed changes.

[0062] It has to be noted that the constant rotational speed mode is typically applied with the solution comprising a horizontal-axis gear, while the mode based on rapid rotational speed changes is typically utilized with the configuration wherein the longitudinal axis of the device is set at an arbitrary angle.

[0063] During the operation of the constant rotational speed, preferably horizontal-axis rotary drum 2 of the unit 1 the active agent grains, by way of example, salt crystals, preferably NaCl crystals, that are contained in the rotary drum 2but only partially fill the rotary drum 2are rotated about a horizontal axis 6 or an axis set at an angle of at most 75 relative to the horizontal at such a speed that the crystals are pulled downwards by the gravitational force just before they could reach the top dead point, which means that the gravitational force exerted on the crystals should exceed the centrifugal force (as calculated for a horizontal axis):

[0064] The gravitational force is: F=m*g

[0065] The centrifugal force is: F=m*(r*4*pi.sup.2)/T.sup.2

[0066] Hence g=r*4*pi.sup.2/T.sup.2.sub.min

1/T.sup.2.sub.min=g/(r*4*pi.sup.2)

[0067] T.sub.min={square root over (r*4*pi2/g)}. Considering that the approximate formula is T.sub.min2*{square root over (r)}.

[0068] This implies that the rotation cycle time should be longer than that, where g refers to gravitational acceleration, and r denotes a value equalling the inside radius of the rotary drum minus the radius of the smallest grain. In practice, it is expedient to allow an appropriate leeway.

[0069] The present embodiment has a rotary drum 2 with a diameter of 3.1 cm, the rotary drum 2 being rotated at a maximum speed of n=244 rev/min during the phase when micronizing is carried out applying the above principle. As indicated by practical experience, the angle of the axis 6 of rotation may be varied in a relatively wide range=15without significantly degrading the efficiency of the apparatus.

[0070] The rotary drum 2 is rotated at a constant speed, and thereby the active agent grains contained therein are turned over, colliding and rubbing against one another, and thus a micronized active agent is produced that leaves the rotary drum through its filtering material having a filtering capacity of 0.5-1000 m. In addition to gravity, expelling the micronized active agent is also assisted by the centrifugal forces occurring upon rotation of the drum, the optionally included fan 4 and/or by the suction effect of the air flow generated by the inhaler or air treatment device/apparatus in which the unit 1 is disposed. A sufficiently low rotational speed of the rotary drum 2 can also be provided by the reducing gear 5.

[0071] The unit 1 according to the invention can also be operated without a reducing gear (see FIG. 3).

[0072] The unit 1 may also be operated (with an arbitrary angle of axis) by spinning up the rotary drum 2 by means of the motor 2 in the same direction or in alternating directions. By spinning up it is meant that the rotary drum 2 is rotated with varying speed, i.e. the rotary drum 2 is rotated such that it has a high angular acceleration, which is followed by braking it either actively or taking advantage of mechanical losses, thereby providing that, in addition to the micronizing action described above, the active agent grains are also subjected to a rubbing and turning action generated by the high initial acceleration and fast braking of the rotary drum 2. In this case, in a resting state the active agent grains inside the rotary drum 2 take a position determined by gravity. During the spin-up phasedue to their inertiathe grains only gradually reach the rotational speed of the rotary drum 2, meanwhile being rubbed against the wall of the rotary drum 2 and turned over and rubbed against one another, and spreading all over the cylindrical surface of the rotary drum 2, thereby producing a micronized active agent that leaves the drum in a filtered manner through the 0.1-1000 m filtering-capacity walls of the rotary drum 2. A similar phenomenon occurs during hard braking. The expelling of the micronized active agent is assisted by the centrifugal forces occurring upon rotation of the drum, the optionally included fan 4 and/or by the suction effect of the air flow generated by the inhaler or air treatment device/apparatus in which the unit 1 is disposed, and, depending on the angle of the principal axis, also by gravity. Applying such a mode of operation with the dimensions exemplified above, the spin-up duration can be 1.5 sec., the braking duration 3.5 s, and the length of the rest period can be 2 s. If a half filled-up rotary drum 2 having a 3.1 cm-long horizontal axis is spun up from resting state, the angular acceleration of the rotary drum 2 is preferably 25 1/s.sup.2. Rest periods are expediently included because of the variability of the duration of the deceleration/braking phase.

[0073] It is important to note that by the term motor an electric motor is primarily meant but it can also refer to a functionally equivalent rotating mechanism with a different operating principle. The above described modes of operation can be partly realized by mechanisms operated exclusively by the input of mechanical energy (by way of example, by pressing a button connected to a ratchet and gear mechanism, or by winding up a coil spring). These mechanisms can mostly be utilized when built into portable inhalers, by way of example in such a manner that the user spins up the rotary drum as many times and with a frequency as specified in the user's manual. The implementation of the mechanical rotating mechanism is not included in the invention since it can be realized by a skilled person in a number of known ways. The functionality of the motor may also be performed by the motor or fan of the apparatus containing the unit according to the invention.

[0074] It is of common knowledge that when a hygroscopic material is heated to a higher-than ambient temperature, its moisture content will drop. Taking into account that a major part of solid active agents to be micronized, for example NaCl, is hygroscopic, and therefore prone to clumping, it is expedient to heat it in order to keep it drier. This can be achieved by heating the rotary drum 2 and thereby the active agent contained therein applying a heating element 7. The heating element 7 is disposed below the rotary drum 2 (considering the typical operating position of the rotary drum 2). For a rotary drum 2 with a diameter of 3.1 cm and a length of 3 cm, containing 6 grams of NaCl crystals the required heating power of the heating element is 1-2 Watts, in case the air flow is applied intermittently (corresponding to the spin-up phases). It should be noted here that the heating element may also be disposed upstream of the rotary drum.

[0075] In FIG. 2 a variant of the unit 1 according to the invention further comprising an accumulation and dosing chamber 8 is shown, wherein the accumulation and dosing chamber 8 essentially corresponds to the housing that contains the unit's mechanism. Due to the action of the flap valves and blocking valves the particles leaving the rotary drum will be kept inside the accumulation and dosing chamber 8 while a dose is being prepared, and until the produced micronized active agent is used up. A dose of the active agent can leave the accumulation and dosing chamber 8 on the one hand when the user inhales the prepared micronized active agent by means of an oral or nasal adapter 12 (see FIG. 4) such that due to the suction action the flap valves 9 free up the path of the air flow (and thereby, the path of the active agent). At the same time, the flap valves prevent moist and contaminated exhaled airresulting from user errorfrom reentering the accumulation and dosing chamber 8 of the unit 1. Alternatively (by way of example, with a larger-sized inhaler unit) the active agent can also be fed to the air flow of the inhaler device containing the unit expediently by opening the electromechanical or mechanical blocking valves 10 and making the air flow through them. The optionally included fan 4 facilitates the expelling of the micronized active agent from the rotary drum 2, and also allows for circulating the micronized active agent in a floating state in the accumulation and dosing chamber 8 until it is used, preventing the micronized agent from settling.

[0076] The application of the accumulation and dosing chamber is justified if either the user cannot be expected to inhale low doses for a prolonged period of time (for example, with a pocketable handheld electronic inhaler), or if a single, higher dose is preferred for other reasons. Then, the duration of dose preparation (performed expediently in a closed chamber) is relatively long.

[0077] FIG. 5 shows the flow diagram of the control electronics 13 applicable with the unit 1 according to the invention. The control electronics can be operated by a switch 15, and has a control unit 16 and a power electronics unit.

[0078] A storage unit 17, adapted to store all the operating data that have been gathered since the unit 1 was first switched on, is connected to the control unit 16. Such data are the operating parameters of the motor 3, the count of operating cycles, and the data supplied by an ammeter 18 that may also be fed directly to the control unit 16. Control of the apparatus is performed by the control unit 16 utilizing current ammeter 18 data and data acquired earlier from the ammeter 18, further data stored in the storage unit 17, and also the data retrieved from a storage unit 19.

[0079] The storage unit 19 is applied for storing lab-measured decrease characteristics of the applied agent, the date of expiry, the maximum cycle count, and other factory-set parameters required for process control and for blocking the operation of the apparatus.

[0080] The control unit 16 also comprises a built-in clock 20. The control unit also comprises a signalling unit 21 adapted to provide light and/or sound signalling to indicate the on-off switching of the apparatus and for instance the expiry of the contained agent.

[0081] The control electronics 13 may also comprise a separate power source 22 (battery). By controlling the micronizer utilizing an embodiment or a combination of more than one embodiments of the unit 1, according to the invention in an appropriate manner it can be provided with a sufficient accuracy that the desired amount of micronized active agent is produced during each operating cycle.

[0082] In order to do that, the momentarily available (remaining) quantity of the active agent has to be determined applying one of the following methods: [0083] Under laboratory conditions the active agent release (per time unit) characteristics of the unit, dependent on certain parameters, such as the operating voltage, the mode of operation, the amount of remaining active agent, are determined and permanently stored in the memory of the unit at the factory. Based on these characteristics, and also on the stored operating data of former operating cycles and the starting amount the remaining amount of active agent can be calculated. [0084] Considering that in case of the mode of operation based on rapid change of rotational speed the spin-up characteristics will change as a function of the remaining amount of active agent (spinning up a lower mass requires a lower initial current), the remaining amount of active agent can also be inferred from the initial current.

[0085] Knowing the remaining amount of active agent the cycle time and optionally other parameters, by way of example the operating voltage of the motor, are automatically adjusted by the control unit 16.

[0086] The solutions operating as described above can be combined with a solution whereinunder certain conditionsthe control unit 16 blocks the further operation of the unit.

[0087] This solution is based on that the conditions under which the amount of delivered agent falls below the desired minimum within a fixed operation period are known from lab measurements, or under which a dose cannot be prepared within a comfortable period or with a sufficient safety margin even with the application of the operating parameters adjusted by the control electronics. In that case, and also upon the expiry of the active agent or at the end of a pre-programmed therapy session, the operation of the unit is blocked by the control electronics.

[0088] In the mode of operation of the unit according to the invention that is based on rapid changes of rotational speed the duration of the operating cycles (detectable by listening)the cycles consisting of a spin-up phase, a total or partial braking phase, and optionally, a resting phaseis expediently adjusted to the cycle time of relaxed breathing, i.e., approximately 6 seconds, which according to the literature can be utilised for practicing relaxed breathing in order to achieve proper air exchange and a lower blood pressure.

[0089] FIG. 6 schematically illustrates a further conceivable embodiment of the unit according to the invention that does not include a rotary drum. The unit 1 consists of four major parts: a motor 3, a rotary block 23preferably a disc or a ringa friction block 24 adapted to be in frictional relation with the rotary block 23, and a clamping device 25 adapted for pressing the friction block 24 against the rotary block 23. The unit 1 is disposed in an accumulation and dosing chamber 8 that can be fitted with flap valves 9 and blocking valves 10.

[0090] The unit is preferably incorporated in a housing 11, the input and output portions of the housing 11 being covered by a material having a filtering capacity of 0.1-1000 m, preferably a closely woven filter 26, preferably a metallic mesh or microperforated plate adapted for filtering the air flowing through the unit 1.

[0091] The rotary block 23a disc or ringis disposed on the shaft 6 of the fan 4 driven by the motor 3, and thereby the rotary block 23 is driven by the motor 3 together with the fan.

[0092] A heating element 7 may be disposed below the rotary block 23. The motor 3 may also have control electronics 13.

[0093] The rotary block 23 and the friction block 24 can be made of identical or different materials.

[0094] If the rotary block 23 and the friction block 24 are made of the same material, then the material is, by way of example, table salt (NaCl). In case they are made of different materials, the rotary block 23 can be made, by way of example, of NaCl, while the material of the friction block 24 can be, by way of example, salbutamol.

[0095] The functionality of the heating element 7, the control electronics 13, the accumulation and dosing chamber 8, the flap valve 9 and the blocking valve 10 is essentially the same as was explained in relation to the unit comprising a rotary drum.

[0096] The operation of the unit 1 shown in FIG. 6 is described as follows:

[0097] By switching on the motor 3 the fan 4 and the rotary block 23disc or ringare brought into operation. During the rotation of the disc or ring 23 the friction block 24, being in frictional relation with the disc or ring 23, separates particles therefrom, the particles being expelled through the perforations of the filter 26 constituting the closing wallings of the housing 11, into the surrounding environment by the air flow produced by the fan 4, where its beneficial effect is produced upon inhaling them by the user.

[0098] Due to the frictional relation of the rotary block 23disc or ringand the friction block 24 fine particles separate from both objects.

[0099] The micronization capacity of the unit 1 is fundamentally dependent on rotational speed.

[0100] It should be noted that particle separation may also be accomplished applying a mechanism different from the friction block 24.

[0101] The unit according to the invention has the following advantages: [0102] it has simple structural arrangement, [0103] it can be adapted to suit different user needs.