TWI761510B - Microstructured passage module and aerosolizer using the same - Google Patents

Abstract

A microstructured passage module for aerosol generator is provided. The module includes a plate overlaid by a cover thus forming a compartment, an entrance for a liquid and an exit. The plate includes a plurality of walls parallel to each other over its entire width so as to define a plurality of passages threrebetween. Moreover, a plurality of pillars protruding from the plate are distributed in at least section of the passages. A column is disposed proximate to the exit and blocks a substantial part thereof, leaving longitudinal aisles for the liquid to flow towards the exit. The liquid flows through the compartment from the entrance to the exit such that an aerosol is produced. A distance between two adjacent pillars is D and the longitudinal aisle has a width W. The D and the W are specifically configured such that the aerosol has a predetermined MMAD.

Description

Microstructure channel module and gas atomizer using the same

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

Aerosolizers, also known as Nebulizers or Atomizers, are used to allow patients to administer drugs by inhalation. In particular, the liquid medicine will be decomposed into an aerosol (Aerosol) with tiny particles or droplets, and patients who use the medicine can obtain more efficient inhalation efficiency and absorption efficiency. The size of the above-mentioned tiny particles can be adjusted according to different breathing conditions, such as chronic obstructive pulmonary disease (COPD), asthma, or the liquid medicine itself. Furthermore, it is important that patients receive the same dose of medication in each treatment modality. In other words, the aerosolizer needs to provide a fixed dose of medicament in each use, and it has a fixed average particle size, which means that it can produce a specific range of mass median aerodynamic particle size ( MMAD, Mass Median Aerodynamic Diameter) and a specific spray duration (spray duration). In this way, medication waste and risks associated with over-medication can be reduced.

Please refer to FIG. 1 , which mainly discloses an example aerosolizer, which includes: an upper casing 964 , a lower casing 965 , a nozzle 963 , a tube 966 , a biasing element 962 , and a storage container 961 . During preparation, the biasing element 962 (eg, a spring) is forced by the relative displacement between the upper shell 964 and the lower shell 965 . At the same time, a certain amount of liquid (not shown) medicine 50 is sucked out from the storage container 961 to the nozzle 963 through the guidance of the tube 966 to prepare for aerosolization. When the aerosolizer 90 is activated, the force generated by the unforced biasing element 962 pushes the metered liquid medicament 912 toward the nozzle 963 and through the nozzle 963, producing an aerosol for the disease Suffer from inhalation. For another exemplary aerosolizer and mechanism of operation, reference may be made to the disclosure of US Patent Application No. 5,964,416 (its US Patent Application Serial No. 08/726,219).

As disclosed in FIG. 1, the pressurized liquid medicine 912 moves in a manner from point A to point A', and simultaneously moves from one high pressure end to the other low pressure end. In this way, the liquid medicine 912 will be sucked out and pushed into the nozzle 963, and when the liquid medicine 912 passes through the nozzle 963, an aerosol will be generated and the aerosol will be discharged at the same time. During aerosolization, it is important to maintain a proper seal between all components. Otherwise, the aerosolization effect will be destroyed. For example, leakage at nozzle 963 may result in pressure loss, resulting in inaccurate doses or inappropriate aerosol particle sizes. This in turn affects the MMAD of the aerosol and the duration of the spray. In order to avoid this, a high degree of care and precision must be maintained in the manufacture and assembly of the various components of the aerosolizer. However, due to the miniature size of these aerosolizer elements, which are often on the order of millimeters or less, achieving a proper seal can become extremely difficult and costly. Furthermore, components with different geometries and miniature sizes may be more susceptible to wear or tear in high pressure environments, typically 5 to 50 megapascals (MPa), or 50 to 500 bar. (Bar).

On the other hand, the nozzle 963 plays an important role in aerosolizing the pressurized liquid medicament 912 into an aerosol of fine particles/droplets and ejecting the aerosol at a specific speed. As shown in FIG. 1 , the pressurized liquid medicine 912 is sucked out to the nozzle 963 through the guidance of the connecting tube. In general, the pressurized liquid medicament 912 will flow into the nozzle 963 at a high velocity, filter through the nozzle 963 and reduce the flow rate in a controllable manner so that a precise dose of the medicament can be aerosolized into the desired state. All of the above have to be specially designed for the internal structure of the nozzle 963 to achieve the effect. Improper nozzle 963 design may cause the complete aerosolization process to be hindered and shorten the life of the aerosolizer 90 or affect the accuracy of the dose.

A typical nozzle used in an aerosolizer contains multiple elements with different geometries. For example, some elements have specific shapes, such as elongated protrusions that are used as screening programs. Some other elements have different shapes, such as the constituent elements of the guiding system used to control the flow of the liquid in the nozzle. In short, the nozzle in the related art requires the combination and interaction of multiple elements with different structural and/or functional characteristics to achieve the desired atomization effect. However, as nozzles continue to shrink in size, fluid control in them is becoming increasingly difficult. The structure, size and arrangement of elements in a nozzle requires careful design and implementation in order for the nozzle to function efficiently. As a result, the cost of nozzle design and manufacture is often high.

The main purpose of this patent application is to provide a nozzle structure with a less complex structure, design and arrangement. The improved nozzle formed above will improve the overall atomization quality and efficiency, while reducing the manufacturing cost. As a result, patients can enjoy more cost-effective treatment options.

This patent application provides a microstructure channel module applied to an aerosolizer. The passage module comprises a plate body covered with an upper cover to form a cavity, an inlet and an outlet through which the liquid can flow. The plate body also further includes a filtering structure. The filter constructions of the embodiments include raised walls, micropillars, raised rows, and combinations thereof. In some embodiments, the plate body includes a plurality of protruding walls arranged parallel to each other over the entire width, thereby forming a plurality of passages. The protruding walls are along a flow direction that is substantially perpendicular to the inlet. In some embodiments, a plurality of micro-pillars are formed protruding from the plate body and are uniformly distributed in at least a part of the passage. In certain embodiments, however, the protruding walls may be continuous or discontinuous in construction. A central column is arranged near the outlet and occupies a substantial part of the area near the outlet, so that the liquid can only flow to the outlet through the longitudinal narrow channel. The liquid flows from the inlet through the chamber 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 specially designed so that the aerosol has a predetermined MMAD. In certain embodiments, D and W are specifically designed to efficiently deliver the aerosolized agent to the patient's lungs. In order to achieve the above purpose, the MMAD of the aerosol must be less than 5.5 um, and more importantly, the MMAD must be between 4 and 5.5 um. Furthermore, when the aerosol is less than 5.5 um, the spray duration will more preferably be about 1.6 seconds. The combination of the above enhances the delivery of microparticles to specific areas in the user's lungs, resulting in a more desirable treatment outcome. In certain embodiments, the microstructured pathway module 1 and its constituent elements are specially designed and arranged so that the liquid medicament 912 with specific properties can be aerosolized and provided with a predetermined MMAD and spray duration . The liquid medicine 912 is composed of active pharmaceutical ingredients, tranquilizers and preservatives. The pharmaceutical active ingredients are selected from beta-mimetics, inhibitors, antiallergic agents, antihistamines and/or steroids or combinations thereof. In addition, the liquid medicine 912 is alcohol-free and has a certain range of properties, such as viscosity and surface tension.

The content of the present invention will be described below with different embodiments. Please note that the devices, modules and other elements described below can be composed of hardware (such as circuits), or composed of hardware and software (such as writing programs into processing units). In addition, different elements can be integrated into a single element, and a single element can also 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 that can be expressed and encompassed using many different kinds of words. The specific methods disclosed below for making or using the various embodiments are merely illustrative, and do not limit the scope of other embodiments of the invention.

Throughout the various perspectives and illustrated embodiments of this disclosure, like reference numerals may be used to designate like elements. The following reference numbers will next be assigned in detail to the exemplary embodiments contained in the following figures. Wherever possible, the same reference numbers appearing in the figures and descriptions are used to designate the same or similar elements. In each illustration, various shapes and thicknesses can be expressed in a slightly exaggerated manner to satisfy the conditions of clarity and easy identification. The following description will specifically point out some of the elements that form, or have direct interaction with, the device of the present invention. It will be appreciated that components not specifically shown or described may take many different forms. In this disclosure, reference to "an embodiment" means that features, structures, characteristics, etc. related to the embodiment have been included in at least one embodiment. Therefore, when referring to "an embodiment" in this disclosure, the substantially referenced embodiments are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable aspect in one or more embodiments. It should be understood that the following figures are not necessarily drawn in actual scale, but are drawn for clarity and understanding. In the various figures, like reference numerals are used to designate similar or like elements, and various illustrated embodiments of the invention are thereby presented and described. The illustrations presented here are not all to their actual size and may be exaggerated or simplified for the sake of illustration clarity. Those skilled in the art to which the present invention pertains should know that various applications and changes derived from the various embodiments and figures disclosed below in this disclosure should still be regarded as the scope of the present invention.

It should be understood that when an element is referred to as being "above" another element, it can mean that the element is directly above the other element, or that the element is positioned over the other element through other objects. above the component. However, if one component is referred to as being "directly above" another component, the above-mentioned situation with other objects is not true.

It should be understood that, unless otherwise expressly defined in this disclosure, even if a "single" type of condition is mentioned in the text, it can still be regarded as including a "plurality" type of condition. Furthermore, related terms, such as "top" and "bottom," may be used herein to describe the relationship of individual elements to other elements as illustrated in the various figures.

It should be understood that when an element is described as being "below" other elements, it can also be construed as being "above" the other elements in different perspectives. The term "under" above can cover both "over" and "under".

It should be understood that the term "about" is used herein, which corresponds to a measured value, such as: amount, duration, aerosol measurement, or the like, when the specified value encompasses ±10% variance and more. ±5%, the variance can be regarded as an appropriate variance to achieve the intended purpose of this disclosure.

Unless otherwise defined, various terms (including technical and scientific terms) used in this disclosure have the same definitions as those of ordinary skill in the art to which this invention belongs. It is also to be understood that for terms mentioned in this disclosure and defined in commonly used dictionaries, the interpretation of the definitions is consistent with the knowledge in the technical field to which the present invention pertains, and is also consistent with the terms in this disclosure. Definitions are consistent; and unless defined directly herein, these terms are not to be read in an ideal or overly formal manner.

2 is a cross-sectional side view of an exemplary gas atomizer consistent with some embodiments described in this patent application. The gas atomizer 90 includes a housing 902 , a pump chamber 904 , and a spring chamber 906 . A biasing element 9062 (eg, a spring) is coupled to the housing 902 , more particularly to the spring chamber 906 . Spring chamber 906 also holds storage container 908 , which can store liquid medicament 912 . The liquid medicament 912 may be drawn out of the storage container 908 through the guidance of the tube 910 , corresponding to a preactuation of the aerosolizer 90 . Specifically, prior to activation of the aerosolizer 90, the housing 902 is rotated. The spring 9062 is stressed by the rotation of the housing 902 . In contrast, liquid medicament 912 is drained from storage container 908 to pump chamber 904 and is ready to be aerosolized. When the aerosolizer 90 is activated, aerosolization will begin. When the aerosolizer 90 is activated, a release mechanism (not shown) is triggered, and the spring 9062 is released from a stressed state to an unstressed state. The above operations generate a force that pushes the liquid medicament 912 in the pump chamber 904 through the delivery device 950, where the microstructured pathway module 1 (ie, the nozzle) is located. That is, the liquid medicine 912 is aerosolized by passing through the microstructure channel module 1 . The microstructure channel module 1 is specially designed to produce aerosols with ideal particle size in a controlled and precise delivery manner. As such, the aerosolized liquid medicament 912 will exit the delivery device 950 and be expelled from the aerosolizer 90 for inhalation by the patient. The liquid medicament of the embodiment 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. More details on liquid medicaments will be described later. Furthermore, in a preferred embodiment, the liquid medicament 912 does not contain propellants (eg, chlorofluorocarbon or hydrofluoroalkane propellants). The propellant is the source of the propelled aerosol with the drug used in common pressure metered dose inhalers (MDI). However, propellants can have negative effects on the environment. Therefore, preferably, the disclosed aerosolizer 90 can operate without propellant.

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

To enhance effective aerosol deposition in the lungs, the ideal aerosol must have a specific range of MMAD and spray duration. For example, the MMAD should be less than 5.5 um, and the spray duration should be about 1.2~1.6 seconds. In a more preferred embodiment, the MMAD is about 4-6 um, and the spray duration is about 1.2-1.6 seconds, more preferably about 1.4-1.6 seconds. Aerosols with an MMAD of approximately 4-6 um are suitable for inhalation therapy. Aerosols with MMAD above a certain range are more difficult to reach the patient's lungs, such as aerosols that are more likely to deposit in the throat. On the other hand, aerosols with MMADs below a certain range increase undesired aerosol transmission, resulting in insufficient aerosol reaching the patient's lungs, which is an ineffective treatment. If the spray duration is not within a specific range, it will affect the patient's inhalation efficiency, increase the chance of clogging and residues, and affect the treatment. For example, a suboptimal effective nebulization time will result in a negative impact on the patient's inhalation of the aerosolized agent over a certain period of time. This patent application provides a microstructured channel module capable of achieving the above MMAD and spray duration. More conclusions will be detailed later.

3A-3B are examples of the microstructure via module microstructure via module 1, which conforms to some embodiments described in this patent application.

FIG. 3A is a top view of the microstructure via module 1 , which conforms to some embodiments described in this patent application. Microstructure Access Module The microstructure access module 1 includes an upper cover 20 and a plate body 10 (covered by the upper cover 20 , not shown), which are combined to form a chamber accommodating filter structure. Liquid (not shown) enters the chamber through the inlet 102 and is released at the outlet 104 in the form of an aerosol. The filtering configuration ensures that the aerosol 50 has the above-described properties for use in human inhalation therapy. For example, aerosol 50 having the MMAD and spray duration described above is disclosed herein.

3B is a cross-sectional view of the microstructure access module 1 along the line XX' shown in FIG. 3A . As follows, the microstructure access module 1 includes a plate body 10 and an upper cover 20 and an inlet 102 and an outlet 104 for liquid to flow through. In addition, the plate body 10 and the upper cover 20 form a chamber 202, and the chamber 202 includes a filter structure (omit the chamber to make it clearer) to guide the liquid flow direction or change the flow rate. The filtering structure may or may not be in contact with the above-mentioned plate body 10 and the upper cover 20 . For example, the filtering structure may be a combination of protrusion rows 52 , micro-pillars 4 , protrusion walls 5 , and protruding from the plate body 10 . With the filter structure of this structure, the aerosol device 50 has a specific MMAD and spray duration as disclosed herein.

4A to 4C are top views of the microstructure via module 1 , which conform to some embodiments described in this patent application.

Please refer to FIG. 4A , which discloses a microstructure via module 1 . The microstructure via module 1 includes a board 10, which can be made of silicone and has dimensions of about 2.5 mm in width, about 2 mm in length, and about 700 um in depth. The plate body 10 is covered with a glass upper cover 20 (not shown in the figure), the width is about 2.5 mm, the length is about 2 mm, and the depth is about 675 um. The size of the plate body 10 corresponds to the upper cover 20 to form a cavity. In addition, the plate body 10 and the upper cover 20 (not shown) are combined, and the opposite ends thereof are defined as the inlet 102 and the outlet 104 . There are two side walls 108 between the inlet 102 and the outlet 104. The distance between the side walls 108 is the width of the plate body 10. The liquid medicine 912 (not shown) enters the chamber from the end of the inlet 102, and the generated aerosol 50 passes through the outlet. End 104 leaves the chamber. The inlet 102 has a width of 2 mm, which is 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 direction of liquid flow of the liquid medicament 912 in the access module is generally perpendicular to the inlet 102 and is defined as A-A'. At least a portion 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 at an angle of about 90∘. As a result of the above, an aerosol 50 that can be inhaled by the patient is thus produced.

The plate body 10 further includes a central column 2 , a spacer block 3 , a micro column 4 and a protruding wall 5 . The micro-pillars 4 , the spacer blocks 3 and the protruding walls 5 are arranged to form the filtering structure of the microstructure channel module 1 , and the spacer blocks 3 , the protruding walls 5 , the micro-pillars 4 and the central pillar 2 protrude in a direction transverse to the liquid flow. In some embodiments, the spacer blocks 3 are arranged in multiple columns at the inlet 102 , and the distance between two adjacent spacer blocks 3 is twice the width of the passageway 18 . The cross-sectional shape of each spacer block 3 is a rectangle, the width is about 50um, and the length is about 200um. Generally speaking, the spacer block 3 is used to initially filter and divide the liquid medicament 912 entering the chamber into separate passages 18 .

In some embodiments, these elements may be formed by etching the microstructured via module 1 as part of the board body 10 . In some embodiments, the etching depth of the plate body 10 is about 5-6 μm to integrally form the aforementioned part of the components, and the depth covers the manufacturing tolerance of 1 μm. It should be noted that the manufacturing method of the board body 10 is not limited to this. The plate body 10 may be fabricated by other means known in the relevant art, such as molding, welding or printing. Additional features and structures of the integral elements will be further described in subsequent texts.

Referring to FIG. 4B , the central column 2 protrudes from the plate body 10 and is close to the position of the outlet 104 . The shape of the central column 2 is nearly spherical, and its particle size is about 150 um. The central column 2 occupies a considerable part of the area close to the outlet 104 so that the liquid can only flow to 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 walls 106 are parallel to the corresponding central column 2 area. The above structure will cause the liquid to flow in opposite directions, that is, flow along the two opposite narrow channels 15 . In other words, the microstructure passage module 1 can be understood as including two outlets 104 for aerosolization. Accordingly, the opposite liquid jets ejected from the two narrow channels 15 meet outside the passage module 1 and close to the outlet 104 , and form the aerosol 50 . The size of the central pillar 2 is such that the width W of each narrow channel 15 is between about 6.7-8.3 um, and further, the width W of the narrow channel 15 is between about 7-8 um. It is worth noting that, here, the manufacturing tolerance of the distance D and the width W is about ± 0.3 um. In certain embodiments, the width W refers to the distance between the inclined wall 106 and the central column 2, the measurement of which is shown in FIG. 4B.

4A and 4B, the plate body 10 further includes a protruding wall 5 disposed on the entire width of the plate body 10, the filter structure of the present invention further includes the protruding wall 5, which are longitudinal and mutually parallel to the liquid flow direction AA' . Between each of the parallel raised walls 5 is a passage 18 through which the liquid medicament 912 can flow. The liquid flows in the plurality of passages 18 in the direction AA'. The width of the passage 18 is about 77um, and the typical width of the protruding wall 5 is about 22um.

In some embodiments, for the unfiltered liquid medicament 912 entering the microstructured channel module 1, the space between the two raised walls 5 acts as a screening procedure, for example, any particles larger than the width of the channel 18 will be The space blocks and filters out. The protruding wall 5 further guides the liquid flow direction so that the liquid flows more uniformly in the direction AA', thereby reducing turbulence. In some embodiments, as shown in Figure 4C, the raised walls 5 are discontinuous. For example, a plurality of protrusion rows 52 are arranged to form the protrusion wall 5 . In particular, there are gaps between two adjacent rows of protrusions 52 , and the liquid flowing between the passages 18 will flow laterally through the gaps between the rows of protrusions 52 . Importantly, all the technical features disclosed in this patent application for the protruding wall 5 are applicable to both continuous and discontinuous protruding walls 5 . In other embodiments, only the micropillars 4 are used to provide the filtering function without the use of the protruding walls 5 .

As shown in FIGS. 4A to 4C , the micropillars 4 are circular and evenly distributed. The above configuration forms a filter configuration of a symmetrical pattern. Therefore, the symmetrical liquid flow is formed by the protruding walls 5 and the micro-pillars 4 to reduce the chance of turbulent flow in the chamber and also affect the effect of aerosolization. The micro-pillars 4 are micron-sized components protruding from the plate body 10, and the height thereof is about 5-6 um. The distance between the micro-pillars 4 is D, and the distance D is about 6.7-8.3 um. More preferably, the distance D is between about 7-8 um. The distribution of the micropillars 4 provides for filtering the liquid into fine particles, or increasing the flow resistance between the liquid medicaments 912 . Therefore, the flow rate of the liquid in the chamber is reduced. However, in some embodiments, the plate body 10 includes the protruding walls 5 and the micro-pillars 4 , but the micro-pillars 4 do not exist between the narrow channels 15 .

Referring to FIGS. 4A to 4C , the protruding wall 5 starts from the inlet 102 and extends toward the outlet 104 . The protruding wall 5 may or may not extend beyond the intersection of the side wall 108 and the inclined wall 106 . Alternatively, the protruding wall 5 may not originate from the inlet 102 , in one example, the protruding wall 5 originates at a distance from the inlet 102 . The micropillars 4 occupy at least part of the vias 18 . Not only that, the micro-pillars 4 occupy the area of the plate body 10 near the outlet 104 . In the embodiment where the protruding wall 5 is not used for filtering or the protruding wall 5 is discontinuous, the micro-pillars 4 are evenly distributed on the plate body 10 . As used herein, the term "occupancy" means that the micropillars 4 are present around the plate 10 but do not completely block the flow of liquid. In some embodiments, the plate body 10 can be regarded as including a first area and a second area, and the first area is closer to the inlet 102 than the second area. Furthermore, in some embodiments, the vias 18 are located in the first area and there are no protruding walls 5 in the second area, and the micropillars 4 occupy at least the second area and some, but not all, of the first area.

The following will focus on Table 1 below, which provides droplet size as MMAD as measured by Next Generation Impactor (NGI). (See USP 36(601) Aerosols, Nasal Sprays, Metered-Dose Inhalers, AND Dry Powder Inhalers for aqueous solution). In the present disclosure, in the pressurized liquid, the distance D and the width W are specially designed so that the generated aerosol can have a predetermined MMAD and spray duration.

Table I

Table 1 reveals the measurement results (n=3) that the MMAD of the aerosol 50 is less than about 5.5um. Or preferably, the MMAD of the aerosol is about 4~5um. In addition, the spray duration of the above-mentioned aerosol is less than 1.6 seconds. Or preferably, the above-mentioned spray duration is between about 1.2 to 1.6 seconds. More preferably, the above-mentioned spray duration is between about 1.4-1.6 seconds. Correspondingly, the spray velocity of the aerosol at the outlet 104 is between about 169-175 m/s. Table 1 further provides a comparison of fine particle fraction (FPF) in pressurized liquids less than 5 microns. In one embodiment, the ratio of droplets smaller than 5 microns is less than 50%. Or preferably, the above ratio is between 35% and 45%.

In order to achieve the above results, the distance D and the width W need to be specially designed. In some 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 and the distance D is less than 8 um and/or the other of the width and the distance D is greater than 7 um. The above structural design is beneficial for producing an MMAD of less than 5.5um and a spray duration of about 1.5-1.6 seconds, as described above, so as to produce the ideal particle size and mist for delivering the drug to the patient's lungs.

In other words, the patient can inhale a fixed dose of aerosol of the desired particle size each time the aerosolizer 90 is operated. However, this patent application is not limited to the literal description, that is to say, any combination of the aforementioned widths and distances D appearing in the specific ranges in the aforementioned Table 1 all fall into the scope of this patent application. In addition, as described above, the present disclosure is effective for generating aerosols with desired MMAD and spray duration.

However, liquids with specific properties are relevant to the operation of the aerosolizer 90 and the desired results. Specifically, the aerosolizer 90 delivers less than 20 ul of liquid with a pressure of at least 50 bar to generate a therapeutic aerosol without propellant. To be effective, the aerosol must have the properties disclosed herein. To achieve this, the liquid itself and its environment must be controlled.

In certain embodiments, the liquid composition does not contain propellant gas, further, the liquid composition contains pharmaceutically active ingredients, tranquilizers and preservatives. The pharmaceutical active ingredients are selected from betamimetics, anticholinergics, antiallergics, antihistamines and/or steroids or combinations thereof. For example, the active pharmaceutical ingredient can be selected from Albuterol Sulfate, Ipratropium Bromide, Tiotropium, Olodaterol, Budesonide , Formoterol, Fenoterol, etc. The ideal concentration of active ingredients in the solution is 0.001 ~ 2g/100 ml. A suitable stabilizer 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 0.5 mg/ml, and more particularly at a concentration of less than About 0.25 mg/ml. A suitable preservative may be Benzalkonium Chloride. In addition, the pH value of the solution composition needs to be adjusted to a specific range, so the solution composition can include citric acid and hydrochloric acid. In a specific preferred embodiment, the composition of the liquid may be 0.22-023 mg/ml Tiotropium Bromide or its analogues, 0.08-0.12 mg/ml Benzalkonium or its analogues And 0.08~0.12 mg/ml of EDTA or its analogs. In addition, the pH value is between 2.7 and 3.1. The acidic pH is used to stabilize the composition and to the extent that the desired dose is delivered. Furthermore, in certain preferred embodiments, the liquid has a low viscosity, about 0.88 cP at room temperature, and the surface tension of the liquid is in the range of about 43-48 dyne. In other embodiments, the liquid is aerosolized to form a propellant-free aerosol for administration to the patient's lungs.

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 inappropriate ingredients or pharmaceutical properties that would cause damage or reaction to the aerosolizer 90 or storage container 908. For example, the liquid may be a non-ethanolic solution and thus be stable for storage in the container. Further, the effective amount of the active pharmaceutical ingredient and the desired concentration of the stabilizer can avoid damage or corrosion of the device. For example, if EDTA is used, its concentration in the solution composition needs to be optimized, and a high concentration of EDTA will increase the solution channel of the nozzle. There is a chance that crystallization will form, which can lead to blockage or obstruction.

In addition to the above, the design combination of the specific structure of the microstructure channel module 1 and the selection of the liquid composition enable the aerosolizer 90 to generate an aerosol with a predetermined MMAD and a spray duration under a wider temperature range . Next, the following will discuss Table II below.

Table II

Table 2 shows the effects of the specially configured microstructured via module 1 of the present disclosure at different operating temperatures. It can be seen from the above that the gas atomizer (n=3) can operate at an operating temperature of about 4 to 25 degrees Celsius. In one example, the storage container containing the medicament is stored in a refrigerator, and the storage container is brought to an environment of 4 degrees Celsius prior to operation. As shown in Table 2, the microstructure channel module 1 in the present disclosure can generate aerosols with similar characteristics at a temperature between 4 and 25 degrees Celsius. In other words, the specially constructed microstructured channel module 1 in the present disclosure can generate ideal aerosols in severe environments. Patients benefit because aerosol therapy can be performed in a wider variety of settings. In addition, within this operating temperature range, the aerosolizer becomes more suitable for liquid medicaments with a specific liquid viscosity, in some embodiments, the viscosity of the medicament solution is adjusted to about 0.5~3 cP, in certain better In embodiments, the viscosity ranges from about 0.8 to 1.6 cP. The high viscosity may affect the average particle size of the aerosol and the duration of the spray, so it is best to keep the viscosity low. Besides, the configuration of the microstructure channel module 1 in the present disclosure makes it more suitable for liquid medicines with a specific surface tension. In some embodiments, the surface tension of the liquid medicines ranges from about 20 to 70 mN/m, or more preferably, between about 25-50 mN/m. Lower surface tension can provide better diffusivity of the agent, thereby increasing the deposition of aerosol on the lung surface, improving the effectiveness of the agent and inhalation therapy.

Therefore, under the conditions of the above ideal liquid composition, the microstructure channel module 1 has a width W of about 6.7-8.3 um and a distance D of about 6.7-8.3 um, and a viscosity range of 0.5-3 cP (operational temperature is about 4-25 degrees Celsius), can produce a better aerosol, its MMAD is less than about 5.5um, or better, between 4-5.5um, the spray duration is less than 1.6 seconds, or better, the medium In 1.4~1.6 seconds, and the ratio of droplets smaller than 5 microns is less than 50%. Or more preferably, the above ratio is between 25% and 40%. . Under these conditions, aerosol inhalation therapy is more effective.

That is, the present disclosure is a microstructured pathway module 1 that is specially configured to generate ideal aerosols in harsh environments, and patients thus benefit greatly because their aerosol inhalation treatments can be performed in a wider variety of settings. operating in the environment.

To sum up, the microstructure via module 1 provided by the present disclosure is easier to manufacture due to the reduced complexity of the structure and its micro-sized components. The finished device delivers a more precise dose of aerosol with ideal MMAD and spray duration each time the aerosolizer is operated.

The reference numerals are described as follows: 1‧‧‧Microstructure channel module 2‧‧‧Central column 3‧‧‧Spacer block 4‧‧‧Micro column 10‧‧‧Board body 102‧‧‧Inlet 104‧‧‧ Outlet 106‧‧‧Sloped wall 108‧‧‧Side wall 15‧‧‧Narrow channel 18‧‧‧Passage 50‧‧‧Aerosol 912‧‧‧Liquid medicine 52‧‧‧Protrusion row 5‧‧‧Protruding wall 90‧‧ ‧Aerosolizer 20‧‧‧Cover 902‧‧‧Shell 904‧‧‧Pump chamber 906‧‧‧Spring chamber 9062, 962‧‧‧Bias assembly 9062‧‧‧Spring 908, 961‧‧‧Storage container 910, 966‧‧‧Tube 950‧‧‧Transfer 963‧‧‧Nozzle 964‧‧‧Upper shell 965‧‧‧Lower shell A-A'‧‧‧Direction of liquid flow

One or more embodiments are shown by way of example and not by way of limitation in the figures of the accompanying drawings, wherein elements having the same reference digit identification number represent similar elements throughout. The drawings are not to scale unless otherwise disclosed.

FIG. 1 illustrates a cross-sectional side view of an exemplary conventional gas atomizer according to the foregoing.

FIG. 2 illustrates a cross-sectional side view of another exemplary conventional gas atomizer according to the present disclosure.

3A and 3B illustrate a microstructure via module and a microstructure via module according to some embodiments of the present disclosure.

4A, 4B, and 4C illustrate side cross-sectional views of a series of microstructured via modules according to some embodiments of the present disclosure.

The above figures are only schematic diagrams and are not used to limit the scope of the patent application of the present invention. In these figures, the size of each part does not necessarily correspond to the actual size for the sake of clarity. The use of reference signs in the various claims is also not intended to limit the scope of the present invention, eg the use of the same or similar reference signs in different drawings.

1‧‧‧Access Module

2‧‧‧Central column

3‧‧‧Spacer

4‧‧‧Micro-pillars

10‧‧‧Board

102‧‧‧Entrance

104‧‧‧Export

106‧‧‧Sloping wall

108‧‧‧Sidewall

15‧‧‧Narrow Road

18‧‧‧Access

50‧‧‧Mist

5‧‧‧Protruding wall

A-A’‧‧‧liquid flow direction

Claims (19)

A microstructure channel module applied to an aerosolizer, characterized by comprising: a plate body covered with an upper cover to form a chamber, and an inlet of the chamber defined by the combination of the plate body and the upper cover and the outlet, the direction of the liquid flowing from the inlet through the chamber to the outlet is defined as the liquid flow direction; a plurality of protruding walls along the liquid flow direction are arranged in parallel on the entire width of the plate body, And between the plurality of protruding walls is defined as a plurality of passages; a plurality of micro-pillars, which are formed by protruding from the plate body, and the distance between adjacent ones is defined as D; a central column, which is formed by projecting from the plate body, close to and occupying most of the outlet, forming a narrow channel between the central column and the outlet for the liquid to flow through, and the narrow channel has a width of W; wherein the liquid flows along the liquid The direction flows through the chamber to generate an aerosol with a mass median aerodynamic particle diameter (MMAD) of less than 5.5um; wherein, the width W is between 6.7 and 8.3um, and the distance D is between 6.7 and 8.3um. The microstructure channel module according to claim 1, wherein at least one of the width W or the distance D is less than 8um. The microstructure channel module according to claim 2, wherein at least one of the width W or the distance D is greater than 7um. The microstructure passage module according to claim 1, wherein the gas atomizer further has a spray duration of 1.2 to 1.6 seconds. The microstructure channel module according to claim 1, wherein the width W and the distance D are respectively between 7 and 8 μm, so that the ratio of the droplet size of the aerosol to less than 5 μm is less than 50 μm. %. The microstructure channel module according to claim 1, wherein the width W and the distance D are respectively between 7 and 8 μm, so that the ratio of the droplet size of the aerosol to be less than 5 μm is between 35 and 35 μm. ~45%. The microstructure passage module according to claim 1, wherein the cross section of the micropillar is circular. The microstructure passage module according to claim 7, wherein the micropillars are uniformly distributed. A microstructure channel module applied to an aerosolizer, characterized by comprising: a plate body covered with an upper cover to form a chamber, and an inlet of the chamber defined by the combination of the plate body and the upper cover and an outlet, the direction of the liquid flowing from the inlet through the chamber to the outlet is defined as the liquid flow direction; the filter structure, which is arranged on the plate body and includes parallel arrays in the liquid flow direction along the liquid flow direction. a plurality of protruding walls over the entire width of the plate body; and a central column protruding from the plate body, occupying close to and mostly the outlet, forming a narrow channel between the central column and the outlet, to For the liquid to flow through, and the width of the narrow channel is W; wherein, the liquid flows from the inlet through the chamber to the outlet, and the filter structure increases the flow resistance of the liquid, resulting in MMAD (Mass median aerodynamic particle size) is less than 5.5um of aerosol; wherein, the width W is between 6.7~8.3um. The microstructure channel module according to claim 9, wherein the width W is between 7 and 8um. An aerosolizer, comprising the microstructure passage module according to any one of claims 1 to 10 and a liquid to be atomized through the microstructure passage module. The gas atomizer of claim 11, wherein the temperature of the liquid is lower than 25 degrees Celsius. The gas atomizer according to claim 11, wherein the viscosity of the liquid is less than 3 cP. The gas atomizer according to claim 11, wherein the viscosity of the liquid is between 0.8 and 1.6 cP. The aerosolizer according to claim 11, wherein the liquid contains active pharmaceutical ingredients and stabilizers, and the active pharmaceutical ingredients are selected from beta-mimetics, inhibitors, antiallergic agents, and antihistamines. or a combination thereof. The aerosolizer of claim 15, wherein the stabilizer is EDTA and the concentration is lower than 0.25 mg/ml. The aerosolizer of claim 11, wherein the liquid is propellant-free. The gas atomizer of claim 11, wherein the liquid does not contain ethanol. The gas atomizer of claim 11, wherein the viscosity of the liquid is between 0.5 and 3 cP.

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