CN110433361B - Microstructure nozzle - Google Patents

Abstract

The invention discloses a micro-structured passage module applicable to an air atomizer, which comprises: a plate covered with a cover to form a chamber, an inlet and an outlet through which a liquid can flow. The plate body comprises a plurality of protruding walls which are arranged in parallel on the whole width, and a plurality of passages are defined among the protruding walls. In addition, a plurality of micro-vias are formed protruding from the plate body and distributed in at least a portion of the vias. A central column is disposed in the region near the outlet and occupies a substantial portion of the region near the outlet so that liquid can only flow through the longitudinal channels to the outlet. The liquid flows through the chamber from the inlet to the outlet to form an aerosol. D is defined as the distance between two adjacent micropillars, and W is the width of the longitudinal narrow channel. D and W are specifically designed so that the aerosol has a predetermined Mass Median Aerodynamic Diameter (MMAD).

Description

Microstructure nozzle

Technical Field

The invention discloses a microstructure passage module, in particular a microstructure passage module suitable for an air atomizer.

Background

Aerosol nebulizers (Aerosolizers), also known as nebulizers (Nebulizers) or nebulizers (nebulizers), are used to administer drugs by inhalation to a patient. In particular, the liquid medicine is decomposed into Aerosol (Aerosol) having fine particles or droplets, and the patient using the medicine can obtain more efficient inhalation efficiency and absorption efficiency. The size of the fine particles can be adjusted according to different breathing conditions, for example: chronic Obstructive Pulmonary Disease (COPD), asthma, or in response to the liquid medicament itself. Furthermore, it is important that the patient receive the same dosage in each treatment regimen. In other words, an aerosolizer is required to provide a fixed dose of medicament in each use, and which has a fixed average particle size, i.e., a Mass Median Aerodynamic Diameter (MMAD) and a specific spray duration (spray duration) that are within a specific range of Mass per operation. Therefore, the medicine waste and the risk caused by over-use of the medicine can be reduced.

Referring to fig. 1, there is generally disclosed an exemplary aerosolizer comprising: an upper housing 964, a lower housing 965, a Nozzle (Nozzle) 963, a tube 966, a Biasing assembly (Biasing element) 962, and a storage container 961. During priming, the biasing element 962 (e.g., a spring) is forced by relative displacement between the upper housing 964 and the lower housing 965. At the same time, a metered amount of liquid medicament 50 (not shown) is drawn from the reservoir 961 through the tube 966 and to the nozzle 963 in preparation for aerosolization. When the atomizer 90 is actuated, the force of the unstressed biasing element 962 pushes the quantity of liquid medicament 912 toward the nozzle 963 and through the nozzle 963, creating an aerosol for inhalation by a patient. Another exemplary aerosolizer and mechanism of operation can be found in U.S. patent No. 5,964,416 (U.S. patent application Ser. No. 08/726,219), the disclosure of which is incorporated herein by reference.

As shown in fig. 1, the pressurized liquid medicament 912 moves along from point a to point a' and also from one high pressure end to the other low pressure end. As a result, the liquid medicament 912 is drawn out and pushed into the nozzle 963, and as the liquid medicament 912 passes through the nozzle 963, an aerosol is generated and simultaneously expelled. During aerosolization, it is important to maintain a proper Seal (Seal) between all components. Otherwise, the aerosolization effect is impaired. For example, leakage from the nozzle 963 may cause pressure loss, thereby resulting in inaccurate dosing or improper aerosol particle size. Which in turn affects the MMAD of the aerosol and the duration of the spray, a high degree of care and precision must be maintained in manufacturing and assembling the various components of the aerosol to avoid such conditions. However, because of the Miniature (Miniature) size of the aerosolizer components, which is typically on the order of millimeters or less, achieving a proper seal becomes extremely difficult and costly. Furthermore, components having different geometries and micro-scale dimensions may be more susceptible to wear or tear in high pressure environments, typically at pressures between 5 and 50 million pascals (MPa), i.e., 50 and 500 Bar (Bar).

On the other hand, the nozzle 963 plays an important role of aerosolizing the pressurized liquid medicine 912 into an aerosol of fine particles/droplets and ejecting the aerosol at a specific speed. As shown in fig. 1, the pressurized liquid medicament 912 is drawn out through the connection tube to the nozzle 963. Generally, the pressurized liquid medicament 912 flows into the nozzle 963 at a high velocity, filters through the nozzle 963 and reduces the flow rate in a controlled manner so that a precise dose of medicament can be aerosolized to the desired state. Both of these require special design of the internal structure of the nozzle 963 to achieve the desired results. Improper nozzle 963 design may result in the complete aerosolization process being impeded, shortening the life of the aerosolizer 90, or affecting the accuracy of dosing.

A typical nozzle for use in an aerosol atomizer comprises a plurality of components having different geometries. For example, some components have a particular shape, such as an elongated protrusion that is used as a filter. Some other components have different shapes, such as components of a guide system for controlling the flow direction of the liquid in the nozzle. In short, the nozzles of the related art require the combination and interaction of multiple components having different structural and/or functional characteristics to achieve the desired atomization. However, as the size of the nozzles continues to shrink, fluid control therein is becoming increasingly difficult. The structure, size and arrangement of the components in the nozzle require careful design and implementation to make the nozzle function more efficiently. Thus, the cost of design and manufacture of the nozzle is often prohibitive.

It is a primary object of the present application to provide a nozzle arrangement that is of less complex construction, design and arrangement. The improved nozzle formed as described above will improve overall atomization quality and efficiency while reducing manufacturing costs. Thus, the patient may enjoy a more cost-effective treatment regimen.

Disclosure of Invention

The invention provides a microstructure passage module applied to an air atomizer. The channel module comprises a plate body covered with an upper cover to form a chamber, an inlet and an outlet through which liquid can flow.

The plate body further comprises a filter construction. The filter constructions in embodiments include raised walls, micro-posts, rows of projections, and combinations thereof.

In some embodiments, the plate body includes a plurality of protruding walls arranged parallel to each other across the width, thereby forming a plurality of passages. The projecting wall is along a flow direction that is substantially perpendicular to the inlet. In some embodiments, a plurality of micropillars are formed protruding from the plate body and are uniformly distributed in at least a portion of the passage. However, in some embodiments, the formation of the protrusion walls may be continuous or discontinuous. A central column is disposed in the region near the outlet and occupies a substantial portion of the region near the outlet so that liquid can only flow through the longitudinal channels to the outlet. The liquid flows through the chamber from the inlet to the outlet to form an aerosol. D is defined as the distance between two adjacent micropillars, and W is the width of the longitudinal narrow channel. D and W are specifically designed so that the aerosol has a predetermined MMAD. In certain embodiments, D and W are specifically designed to efficiently deliver aerosolized medicament to the lungs of a patient. To achieve this, the MMAD of the aerosol must be less than 5.5um, and more preferably, the MMAD must be between 4 and 5.5um. Furthermore, when the aerosol is less than 5.5um, the spray duration will more preferably be about 1.6 seconds. The combination promotes the delivery of the microparticles to specific areas in the user's lungs, thus producing more desirable therapeutic results.

In certain embodiments, the microstructured pathway module 1 and its constituent components are specifically designed and arranged so that the liquid medicament 912 having specific characteristics can be aerosolized and provided with a predetermined MMAD and spray duration. The liquid medicament 912 is composed of pharmaceutically active ingredients, stabilizers and preservatives. The pharmaceutically active ingredient is selected from beta-mimetics, inhibitors, anti-allergic agents, antihistamines and/or steroids or combinations thereof. In addition, the liquid medicament 912 is ethanol-free and has a specific range of properties, such as: viscosity and surface tension.

Action and Effect of the invention

The present invention is a micro-structured pathway module 1 that is particularly configured to produce a desired aerosol in a harsh environment, and therefore patients benefit much because their aerosol inhalation therapy can operate in a wider variety of environments.

In summary, the microstructure module 1 provided in the present invention is easier to fabricate due to the reduced complexity of the configuration and the micron-sized devices. And the finished device can deliver a more accurate dose of aerosol with the desired MMAD and spray duration each time the aerosolizer is operated.

Drawings

One or more embodiments are illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings in which elements having the same reference number designation may represent like elements throughout. The drawings are not to scale unless otherwise disclosed.

FIG. 1 illustrates a cross-sectional side view of an example of a conventional aerosolization apparatus in accordance with the foregoing teachings;

FIG. 2 illustrates a cross-sectional side view of another exemplary conventional aerosolizer, in accordance with the present disclosure;

FIGS. 3A and 3B illustrate a microstructure via module and a microstructure via module, in accordance with some embodiments of the present disclosure;

fig. 4A, 4B, and 4C illustrate cross-sectional side views of a series of microstructured channel modules, in accordance with some embodiments of the present disclosure.

The drawings are only schematic and are not intended to limit the scope of the invention. In the drawings, the size of each part does not necessarily correspond to the actual size for clarity. The use of reference signs in the claims is not intended to limit the scope of the claims, such as the use of the same or similar reference signs in different drawings.

Wherein the reference numerals are as follows:

1: channel module

2: central column

3: spacing block

4: microcolumn

10: plate body

102: inlet port

104: an outlet

106: inclined wall

108: side wall

15: narrow passage

18: vias

50: aerosol mist

912: liquid medicine

52: projecting row

5: projecting wall

90: gas atomizer

20: upper cover

902: shell body

904: pump chamber

906: spring chamber

9062. 962: biasing assembly

9062: spring

908. 961: storage container

910,966: pipe and method for producing the same

950: transmission device

963: nozzle for spraying liquid

964: upper casing

965: lower case

A-A': direction of liquid flow

Detailed Description

The invention will be illustrated in the following with different embodiments. It should be noted that the components of the devices, modules, and the like described below may be implemented by hardware (e.g., circuits) or by hardware and software (e.g., programs written into the processing units). In addition, different components may be integrated into a single component, or a single component may be separated into different components. Such variations are intended to be within the scope of the present invention.

Methods of making and using the disclosed embodiments are discussed in detail below. It should be appreciated, however, that the following embodiments disclose many applicable inventive concepts, and that these inventive concepts can be embodied and covered in a wide variety of contexts. The particular methods disclosed below for making and using various embodiments are illustrative only and do not limit the scope of other embodiments of the invention.

In various views and illustrative embodiments of the present disclosure, like reference numerals may be used to designate like elements. The following reference numerals will be specified in detail below with respect to exemplary embodiments contained in the following figures. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. In the drawings, various shapes and thicknesses may be shown in a somewhat exaggerated manner to satisfy the requirements of clarity and easy recognition. The following description will particularly point out components that form part of, or interact directly with, the apparatus of the present invention. It will be appreciated that components not specifically illustrated or described may take a variety of different forms. Reference throughout this specification to "one embodiment" or "an embodiment" means that a feature, structure, characteristic, or the like described in connection with the embodiment is included in at least one embodiment. Thus, references to "an embodiment" in this disclosure are not necessarily to the same embodiment, but they may. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. It should be understood that the following drawings are not necessarily to scale, but are drawn with priority for clarity and understanding.

Like reference numerals are used to designate like or similar components throughout the several views, and the various illustrated embodiments of the present invention are presented and described thereby. The illustrations presented herein do not all conform to actual dimensions and may be exaggerated or simplified for clarity. Those of ordinary skill in the art should appreciate that they can readily use the disclosed embodiments as a basis for designing or modifying other structures for carrying out the various functions or obtaining a novel and useful result.

It will be understood that when an element is referred to as being "on" another element, it can be directly on the other element or on the other element with other objects in between. However, if one element is "directly over" another element, the above-mentioned situation with other objects in between is not true.

It should be understood that even if a "single" type of condition is referred to herein, it is intended to include a "plurality" of the type unless the context clearly dictates otherwise. Furthermore, relative terms, such as "top" and "bottom," may be used herein to describe a relationship between a single element and other elements as illustrated in the figures.

It will be understood that when an element is referred to as being "below" another element, it can be "above" the other element from a different perspective. The term "under" can also cover both the meaning of "above" or "below".

It is to be understood that the term "about" as used herein corresponds to a measured value, such as: when a particular value encompasses a variation of + -10% and more particularly + -5% in amount, duration, aerosol measurement, or the like, the variation can be considered an appropriate variation to achieve the intended purpose of the present disclosure.

Unless otherwise defined, each term (including technical and scientific terms) used in the present disclosure has the same definition as commonly understood by one of ordinary skill in the art to which this invention belongs. It is also to be understood that the terms so defined, which are referred to in this disclosure and are defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the present disclosure and will be defined by the language of the specification; and, unless defined directly herein, these terms are not to be interpreted in an idealized or overly formal sense.

FIG. 2 is a cross-sectional side view of an exemplary aerosolizer, consistent with some embodiments described herein. The gas atomizer 90 includes: housing 902, pump chamber 904, spring chamber 906. A biasing element 9062 (e.g., a spring) is coupled to the housing 902 and more particularly disposed within the spring chamber 906. The spring chamber 906 also holds (hold) a reservoir 908, wherein the reservoir 908 can store a liquid medicament 912. The liquid medicament 912 may be drawn out of the reservoir 908 in response to a pre-actuation (priming) of the aerosolizer 90 via the direction of the tube 910. In particular, housing 902 may be rotated prior to activation of aerosolizer 90. Spring 9062 is forced by rotation of housing 902. In contrast, the liquid medicament 912 is drawn from the reservoir 908 to the pump chamber 904 and is ready to be aerosolized. Upon activation of the aerosolizer 90, aerosolization is initiated. When the aerosolizer 90 is actuated, a release mechanism (not shown) is triggered and the spring 9062 is released from the stressed state to the unstressed state. This creates a force in the pump chamber 904 that pushes the liquid medicament 912 through the transfer device 950, i.e., where the micro-structured channel module 1 (i.e., nozzle) is located. That is, the liquid medicament 912 is aerosolized by passing through the micro-structured channel module 1. The micro-structured passage module 1 is designed in a special way so that it can produce an aerosol with a desired particle size and in a controlled and precise delivery manner. As a result, the aerosolized liquid medicament 912 exits the delivery device 950 and is expelled from the aerosolizer 90 for inhalation by the patient. The liquid medicament of the embodiments includes a breathable composition. As follows, the liquid medicament may be a liquid solution. In a more preferred embodiment, the liquid medicament is ethanol-free. Further details of the liquid medicament will be described later.

Moreover, in preferred embodiments, the liquid medicament 912 is free of propellants, such as chlorofluorocarbons (chlorofluorocarbons) or hydrofluorocarbon (hydrofluoroalkane) propellants. Propellants are a source of propellant for propelling the aerosol with the medicament, and are used in conventional Metered Dose Inhalers (MDIs). However, the propellant may have a negative effect on the environment. Therefore, it is preferred that the disclosed aerosolizer 90 be operable without the need for a propellant.

The micro-structured pathway module 1 is one of the most important components in the aerosolizer 90 because it can break down the liquid medicament 912 into an aerosol of fine particles or droplets. The microstructured passage module 1 in the atomizer 90 has a microstructured filtering and guiding system and is composed of a micron-sized component and a plurality of passages 18 defined by the micron-sized component. When the liquid medicament 912 flows through the micro-structured channel module 1 at high speed, the micro-sized components will partially block the flowing medicament and break it down into small particles. In addition, the configuration of the micron-sized components and the passageways 18 will increase the fluid resistance, thereby reducing the liquid flow velocity.

To promote effective aerosol deposition in the lungs, an ideal aerosol must have a specific range of MMAD and spray duration. For example, the MMAD should be less than 5.5um, and the duration of the spray should be approximately 1.2-1.6 seconds. In a more preferred embodiment, the MMAD is between about 4 and 6um and the spray duration is between about 1.2 and 1.6 seconds, and more preferably between about 1.4 and 1.6 seconds. Aerosols with an MMAD of about 4-6 um are suitable for inhalation therapy. Aerosols with MMAD above a certain range are more difficult to reach the patient's lungs, as aerosols are more prone to deposit in the larynx. On the other hand, aerosols with MMAD below a certain range conversely increase undesirable aerosol transmission, resulting in insufficient aerosol reaching the patient's lungs, which is an ineffective treatment. If the duration of the spray is not within a specific range, the inhalation efficiency of the patient will be affected, and the chance of blockage and residue will be increased, which will affect the treatment. For example: an undesired effective nebulization time will result in a negative impact on the patient's inhaled quantity of aerosolized medicament over a period of time. The present application provides a microstructure pathway module that achieves the MMAD and spray duration described above. More conclusions will be detailed later.

Fig. 3A-3B are illustrations of a micro-structured via module 1, which are consistent with some embodiments described herein.

Fig. 3A is a top view of a micro-structured via module 1, according to some embodiments described in this application.

Microstructure passage module the microstructure passage module 1 comprises a top cover 20 and a plate body 10 (covered by the top cover 20, not shown), the aforementioned combination forming a chamber housing filter construction. Liquid (not shown) enters the chamber through inlet 102 and exits in aerosol form through outlet 104. The filtering construction ensures that the aerosol 50 has the above-mentioned characteristics to be suitable for human inhalation therapy. For example, aerosol 50 having the MMAD and spray duration described above is disclosed herein.

Fig. 3B is a cross-sectional view of the microstructure passage module 1 along the line X-X' shown in fig. 3A, wherein the microstructure passage module 1 comprises a plate body 10 and a cover 20, and an inlet 102 and an outlet 104 for liquid to flow through, and the plate body 10 and the cover 20 form a chamber 202, and the chamber 202 comprises a filtering structure (the chamber is omitted for clarity) for guiding the flow direction of the liquid or changing the flow rate. The filtering structure may or may not contact the plate body 10 and the upper cover 20, for example: the filtering structure may be a combination of the rows of protrusions 52, the micro-pillars 4, the protrusion walls 5 and their protrusions from the plate body 10. With this configuration of the filter structure, the aerosol 50 has a specific MMAD and spray duration as disclosed herein.

Fig. 4A-4C are top views of a micro-structured via module 1, according to some embodiments described in this application.

Referring to fig. 4A, a microstructure passage module 1 is disclosed. The microstructure passage module 1 comprises a plate body 10, which may be made of silicone and has the dimensions: about 2.5mm in width, about 2mm in length and about 700um in depth. The plate body 10 covers a glass upper cover 20 (not shown) having a width of about 2.5mm, a length of about 2mm and a depth of about 675um. The plate body 10 is sized to form a cavity corresponding to the upper cover 20. In addition, the plate body 10 and the upper cover 20 (not shown) are combined, and opposite ends thereof define an inlet 102 and an outlet 104. The inlet 102 and the outlet 104 have two side walls 108 therebetween, the distance between the side walls 108 is the width of the plate body 10, the liquid medicament 912 (not shown) enters the chamber from the inlet 102 end, and the generated aerosol 50 exits the chamber from the outlet 104 end. The inlet 102 is 2mm wide and wider than the outlet 104. The liquid medicament 912 flows in a general direction in the chamber from the inlet 102 to the outlet 104. The liquid medicament 912 hasbase:Sub>A liquid flow direction in the channel block that is substantially perpendicular to the inlet 102, and is defined asbase:Sub>A-base:Sub>A'. At least part of the liquid medicament 912 flows along the inclined wall 106 of the channel module 1 causing the liquids to converge and collide with each other, or preferably the angle of convergence is about 90 °. As a result, an aerosol 50 is generated which can be inhaled by the patient.

The plate body 10 further comprises a central pillar 2, a spacer block 3, a micro-pillar 4 and a protruding wall 5. The micro-pillars 4, the spacers 3, and the protruding walls 5 are arranged to constitute a filter structure of the micro-structured channel module 1, and the spacers 3, the protruding walls 5, the micro-pillars 4, and the central pillars 2 protrude in a direction transverse to the flow of the liquid. In certain embodiments, the spacers 3 are arranged in a plurality of rows at the inlet 102, the distance between two adjacent spacers 3 being twice the width of the passage 18. Each spacer 3 has a rectangular cross-sectional shape with a width of about 50um and a length of about 200um. Generally, the spacer block 3 serves to initially filter and divide the liquid medicament 912 entering the chamber into separate passageways 18.

In some embodiments, these components may be formed by etching the microstructured passage module 1 as part of the plate body 10. In some embodiments, the plate body 10 is etched to a depth of about 5-6 um to integrally form the aforementioned partial components, the depth of which covers a manufacturing tolerance of 1 um. It should be noted that the manufacturing method of the plate body 10 is not limited thereto. The plate body 10 may be made in other ways known in the related art, such as: molding, welding or printing. Additional features and structures of the integrated assembly will be described further hereinafter.

Referring to fig. 4B, the center post 2 protrudes from the plate body 10 at a position near the outlet 104. The shape of the central column 2 is nearly spherical and its particle size is about 150um. The central column 2 occupies a substantial part of the area close to the outlet 104, so that liquid can only flow towards the outlet 104 through the two narrow channels 15 between the central column 2 and the inclined wall 106. The narrow channel 15 is at least partly continuous and longitudinal, in other words partly inclined wall 106 parallel to the respective central pillar 2 area. The above-described structure will cause the liquid to flow in opposite directions, i.e. along two opposing narrow channels 15. In other words, the microstructured channel module 1 can be understood to comprise two outlets 104 for aerosolization. Accordingly, the opposing liquid jets that jet out the two narrow channels 15 meet outside the passage module 1 and near the outlet 104, and form the gas mist 50. The dimensions of the central column 2 are such that the width W of each lane 15 is between about 6.7 and 8.3um, and more specifically the width W of the lane 15 is between about 7 and 8um. It is noted that, here, the manufacturing tolerance of the distance D and the width W is about + -0.3 um. In a particular embodiment, the width W refers to the distance between the slanted wall 106 and the center post 2, which is measured as shown in fig. 4B.

Referring to fig. 4A and 4B, the plate body 10 further includesbase:Sub>A protrusion wall 5 disposed over the entire width of the plate body 10, and the filter structure of the present invention further includes the protrusion wall 5, which is longitudinal and parallel to each other in the liquid flow directionbase:Sub>A-base:Sub>A'. Between each parallel protrusion wall 5 is a passage 18 through which the liquid medicament 912 can flow. The liquid flows inbase:Sub>A plurality of channels 18 in the directionbase:Sub>A-base:Sub>A'. The width of the passageway 18 is approximately 77um and the general width of the projecting wall 5 is approximately 22um.

In certain embodiments, the space between the two protruding walls 5, for unfiltered liquid medicament 912 entering the microstructured channel module 1, will act as a filter, e.g., any particles with a size larger than the width of the channel 18, will be blocked by the space and filtered out. The projecting wall 5 further directs the direction of liquid flow, making the liquid flow more uniform in the directionbase:Sub>A-base:Sub>A', thereby reducing turbulence.

In some embodiments, as shown in FIG. 4C, the raised wall 5 is discontinuous. For example, a plurality of protrusion rows 52 are arranged to form the protrusion walls 5. Specifically, there are spaces between two adjacent rows 52 of projections, and liquid flowing between the passages 18 flows laterally through the spaces between the rows 52 of projections. It is important to note that all the technical features disclosed in the present patent application for the protruding wall 5 apply to both continuous and discontinuous protruding walls 5. In other embodiments, the filtering function is provided only by the microcolumn 4 without the protrusion wall 5.

As shown in fig. 4A to 4C, the microcolumns 4 are circular and uniformly distributed. The above arrangement forms a symmetrical pattern of filter structures. Therefore, the symmetric liquid flow is formed by the protrusion walls 5 and the micro-pillars 4 to reduce the chance of turbulence in the chamber, which also affects the effect of aerosolization. The microcolumn 4 is a micrometer-sized member protruding from the plate body 10, and has a height of about 5 to 6um. The distance between the microcolumns 4 is D, and the distance D is about 6.7-8.3 um. More preferably, the distance D is between about 7 and 8um. The distribution of the microcolumns 4 provides filtering of the liquid into minute particles, or increases the flow resistance between the liquid agents 912. Thus, the flow rate of the liquid in the chamber is reduced. However, in some embodiments, the plate body 10 comprises protruding walls 5 and micro-pillars 4, but the micro-pillars 4 are not present between the narrow channels 15.

Referring to fig. 4A-4C, the protrusion wall 5 extends from the inlet 102 to the outlet 104, and the protrusion wall 5 may or may not extend beyond the intersection of the side wall 108 and the inclined wall 106. Alternatively, the protrusion wall 5 may not start at the inlet 102, and in one example, the protrusion wall 5 starts at a distance from the inlet 102. While the microcolumns 4 occupy at least a partial region of the passage 18. Furthermore, the micro-pillars 4 occupy the area of the plate body 10 close to the outlet 104, and in embodiments where no filtration is performed by means of the projecting walls 5 or where the projecting walls 5 are discontinuous, the micro-pillars 4 are uniformly distributed in the plate body 10. The term "occupied" as used herein refers to the presence of the microcolumns 4 around the plate body 10 without completely blocking the flow of liquid. In some embodiments, the plate body 10 may be considered to include a first region and a second region, the first region being closer to the inlet 102 than the second region. Furthermore, in some embodiments, the passageway 18 is located in a first region and no protruding wall 5 is located in a second region, the micropillars 4 occupying at least the second region, and some, but not all, of the first region.

The following will focus on table one, which provides the droplet size, which is the MMAD measured by the Next Generation Implanter (NGI). (please refer to USP 36 (601) Aerosols, nasal Sprays, metered-Dose Inhalers, AND Dry Powder Inhalers for aqueous solution). In the present disclosure, the distance D and width W are specifically designed to produce an aerosol having a predetermined MMAD and spray duration in a pressurized liquid.

Watch 1

Table one reveals that the MMAD of aerosol 50 is less than about 5.5um as a result of the measurement (n = 3). Or preferably, the MMAD of the aerosol is between about 4-5 um. Further, the mist spray duration is less than 1.6 seconds. Or preferably, the duration of the spray is between about 1.2 and 1.6 seconds. Or more preferably, the duration of the spray is between about 1.4 and 1.6 seconds. Correspondingly, the spray velocity of the aerosol at the outlet 104 is between about 169 and 175m/s. The table one further provides a comparison of the Fine Particle Fraction (FPF) of less than 5 microns in the pressurized liquid. In one embodiment, the fraction of droplets smaller than 5 microns is less than 50%. Or preferably, the ratio is between 35% and 45%.

To achieve this, the distance D and the width W need to be designed specifically. In certain embodiments, the width W is between about 7-8 um and the distance D is between about 7-8 um. Or preferably, one of the width W and the distance D is less than 8um and/or the other of the width W and the distance D is greater than 7um. The above-described design is beneficial for producing MMAD less than 5.5um and a spray duration of about 1.5-1.6 seconds, as described above, thereby producing a desirable particle size and mist for delivery of a drug to the lungs of a patient.

In other words, the patient can inhale a fixed dose of aerosol of a desired particle size each time the aerosolizer 90 is operated. However, the present application is not limited to the text, that is, any combination of the above-mentioned width W and distance D which appears in the specific range of the above-mentioned Table I falls within the scope of the present application. In addition, as noted above, the present disclosure is effective in producing an aerosol with a desired MMAD and spray duration.

However, liquids having particular characteristics are relevant to the operation and desired results of the aerosolization 90. Specifically, aerosolizer 90 delivers less than 20ul of liquid by a pressure of at least 50bar to produce a therapeutic aerosol that is propellant-free. To produce effective therapeutic efficacy, the aerosol must have the characteristics disclosed herein. For this purpose, the liquid itself and its environment must be controlled.

In certain embodiments, the liquid composition does not include a propellant gas, and further, the liquid composition includes a pharmaceutically active ingredient, a stabilizer, and a preservative. The pharmaceutically active ingredient is selected from beta-mimetics (betamimetics), inhibitors (antisenilics), anti-allergic agents (antisellegics), antihistamines (antihistamines) and/or steroids (steroids) or combinations thereof. For example, the pharmaceutically active ingredient may be selected from Albuterol Sulfate, ipratropium Bromide (Ipratropium Bromide), tiotropium (Tiotropium), olodaterol (Olodaterol), budesonide (Budesonide), formoterol (Formoterol), fenoterol (Fenoterol) and the like. The active ingredient in the solution is preferably at a concentration of 0.001 to 2g/100ml. Suitable stabilizers may be ethylenediaminetetraacetic acid (EDTA) at a concentration of 0.001 to 1 mg/ml in solution, specifically at a concentration of less than about 0.5mg/ml, and more specifically at a concentration of less than about 0.25mg/ml. A suitable preservative may be Benzalkonium Chloride (Benzalkonium Chloride). In addition, the pH of the solution composition is adjusted to a specific range, and thus the solution composition may include citric acid and hydrochloric acid. In a particularly preferred embodiment, the liquid component may be Tiotropium Bromide (Tiotropium Bromide) or an analog thereof in an amount of 0.22 to 023 mg/ml, benzalkonium Bromide (Benzalkonium) or an analog thereof in an amount of 0.08 to 0.12 mg/ml, and EDTA or an analog thereof in an amount of 0.08 to 0.12 mg/ml. In addition, the pH value is between 2.7 and 3.1. Acidic pH is used to stabilize the composition and to the extent that the desired dose is delivered. In addition, in a particularly preferred embodiment, the liquid is low viscosity (viscocity), about 0.88cP at room temperature, and has a surface tension of about 43 to 48 dynes. In other embodiments, the liquid is aerosolized to form a propellant-free aerosol for administration to the lungs of the patient.

As shown in fig. 2, the liquid is stored in a storage container 908 and then delivered to the aerosolizer 90. Importantly, the liquid system does not contain any undue ingredients or pharmaceutical properties that could cause damage or reaction to the aerosolizer 90 or the storage container 908. For example, the liquid may be a non-alcoholic solution and thus may be stably stored in the container. Further, an effective amount of a pharmaceutically active ingredient and a desired concentration of a stabilizer can prevent damage or corrosion of the device, such as: if EDTA is used, the concentration of which within the solution composition needs to be optimized, a high concentration of EDTA will increase the chance of forming crystals in the solution channels of the nozzle, leading to clogging or obstruction.

In addition to the above, the combination of the specific structural design of the micro-structured pathway module 1 and the selection of the liquid composition all enable the aerosolizer 90 to produce an aerosol with a predetermined MMAD and spray duration over a wider temperature range. Next, the following discussion will discuss Table two below.

Watch two

Table two shows the effect of the specially configured microstructure channel block 1 of the present disclosure at different operating temperatures. As can be seen from the above, the aerosolizer (n = 3) is operable at an operating temperature of between about 4-25 degrees celsius. In one example, a storage container with a medicament stored therein is stored in a refrigerator, and the storage container is subjected to an environment of 4 degrees celsius prior to operation. As shown in table two, the micro-structure passage module 1 of the present disclosure can generate aerosol with similar characteristics at 4-25 ℃. In other words, the microstructure channel module 1 of the present disclosure is particularly configured to generate a desired aerosol under harsh conditions. Patients benefit because aerosol inhalation therapy can be operated in a wider variety of environments. In addition, within this operating temperature range, the aerosolizer becomes more suitable for liquid medicaments having a particular liquid viscosity, in certain embodiments the viscosity of the medicament solution is adjusted to about 0.5-3 cP, and in certain more preferred embodiments, the viscosity ranges from about 0.8-1.6 cP. While high viscosity may affect the average particle size of the aerosol and the duration of the spray, it is desirable to maintain a lower viscosity. In addition, the microstructure channel module 1 of the present disclosure is configured to be more suitable for liquid medicines with specific surface tension, and in some embodiments, the surface tension of the liquid medicine is in a range of about 20-70 mN/m, or more preferably, in a range of about 25-50 mN/m. Lower surface tension provides better diffusion of the agent, thereby increasing deposition of aerosol on the lung surface, enhancing effectiveness of the agent and inhalation therapy.

Thus, with the above-described ideal liquid composition, the microstructure passage module 1 having a width W of about 6.7-8.3 um and a distance D of about 6.7-8.3 um, a viscosity in the range of 0.5-3 cP (operating temperature of about 4-25 degrees celsius), can produce a better aerosol with an MMAD of less than about 5.5um, or more preferably, 4-5.5 um, a spray duration of less than 1.6 seconds, or more preferably, 1.4-1.6 seconds, and a droplet fraction of less than 5 microns of less than 50%. Or more preferably, the ratio is between 25% and 40%. . Under these conditions, aerosol inhalation therapy is more effective.

Effects and effects of the embodiments

The present invention is a micro-structured pathway module 1 that is specifically configured to produce a desired aerosol in a harsh environment, and patients therefore benefit greatly because their aerosol inhalation therapy can operate in a wider variety of environments.

In summary, the microstructure module 1 provided in the present invention is easier to fabricate due to the reduced complexity of the configuration and the micron-sized devices. And the finished device delivers a more accurate dose of aerosol with an ideal MMAD and spray duration each time the aerosolizer is operated.

The above embodiments are preferred examples of the present invention, and are not intended to limit the scope of the present invention.

Claims (20)

1. A micro-structured pathway module for use in an aerosolizer, comprising:

a plate body covered with an upper cover to form a chamber, the plate body and the upper cover defining an inlet and an outlet of the chamber, and a direction in which liquid flows from the inlet through the chamber to the outlet is defined as a liquid flow direction;

a plurality of protrusion walls arranged in parallel along the liquid flow direction over the entire width of the plate body, the protrusion walls defining a plurality of passages therebetween;

a plurality of microcolumns formed to protrude from the plate body, and a distance between adjacent microcolumns is defined as D;

a central post formed to project from the plate body, to approach and largely occupy the outlet, to form a throat between the central post and the outlet for the liquid to flow through, and having a throat width W;

wherein the liquid flows through the chamber in the direction of flow of the liquid to produce an aerosol of a predetermined mass median aerodynamic particle size;

wherein the width W is between 6.7 and 8.3um, and the distance D is between 6.7 and 8.3um.

2. The microstructured channel module of claim 1, wherein:

wherein at least one of the width W or the distance D is less than 8um.

3. The microstructured via module of claim 2, wherein:

wherein at least one of the width W or the distance D is greater than 7um.

4. The microstructured via module of claim 1, wherein:

wherein the predetermined mass median aerodynamic particle size is less than 5.5um.

5. The microstructured via module of claim 1, wherein:

wherein the gas atomizer further has a spraying duration of 1.2 to 1.6 seconds.

6. The microstructured via module of claim 1, wherein:

wherein the proportion of the droplet size of the aerosol being less than 5 microns is less than 50%.

7. The microstructured channel module of claim 1, wherein:

wherein the proportion of the droplet size of the aerosol being less than 5 microns is between 35 and 45%.

8. The microstructured channel module of claim 1, wherein:

wherein, the section of the microcolumn is circular.

9. The microstructured channel module of claim 8, wherein:

wherein the microcolumns are uniformly distributed.

10. The microstructured via module of claim 1, wherein:

wherein the liquid system does not contain ethanol.

11. The microstructured channel module of claim 1, wherein:

wherein the viscosity of the liquid is between 0.5 and 3cP.

12. An aerosolizer, comprising:

the liquid flow control device comprises a plate body, a liquid inlet, a liquid outlet, a liquid flow control valve and a liquid flow control valve, wherein the plate body is covered with an upper cover to form a cavity, the plate body and the upper cover define an inlet and an outlet of the cavity, and the direction from the inlet to the outlet through the cavity is defined as the liquid flow direction;

a filter structure disposed on the plate body and including:

a plurality of protrusion walls arranged in parallel along the liquid flow direction over the entire width of the plate body, the protrusion walls defining a plurality of passages therebetween;

a plurality of microcolumns formed to protrude from the plate body and distributed in the passage, a distance between adjacent microcolumns being defined as D; and

a central post formed projecting from said plate body proximate to and largely occupying said outlet, forming a throat between said central post and said outlet for said liquid to flow through, and said throat having a width W;

wherein the liquid flows through the chamber from the inlet to the outlet, the filter arrangement increasing the resistance to flow of the liquid to produce an aerosol having a mass median aerodynamic particle size of less than 5.5 um;

wherein the width W is between 6.7 and 8.3um, and the distance D is between 6.7 and 8.3um; and

wherein the liquid contains a pharmaceutically active component, a stabilizer and a preservative.

13. The aerosolizer of claim 12 wherein:

wherein the width W is between 7 and 8um.

14. The aerosolizer of claim 12 wherein:

wherein the liquid system is free of ethanol.

15. The aerosolizer of claim 12 wherein:

wherein the operating temperature is below 25 ℃.

16. The aerosolizer of claim 12 wherein:

wherein the viscosity of the liquid is less than 3cP.

17. The aerosolizer of claim 16 wherein:

wherein the viscosity of the liquid is between 0.8 and 1.6cP.

18. The aerosolizer of claim 12 wherein:

wherein the pharmaceutically active ingredient is selected from a beta-mimetic, an inhibitor, an antiallergic, an antihistamine or a combination thereof.

19. The aerosolizer of claim 18 wherein:

wherein the stabilizer is EDTA and the concentration is lower than 0.25mg/ml.

20. The aerosolizer of claim 12 wherein:

wherein the liquid is aerosolized to form a propellant-free aerosol for administration to the lungs of the patient.

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