TW201946693A - Microstructured nozzle - 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 nozzle

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

Aerosolizer, also known as Nebulizer or Atomizer, is used to allow patients to administer drugs by inhalation. In particular, the liquid medicine is decomposed into an aerosol with fine particles or droplets, and patients using the medicine can obtain more efficient inhalation efficiency and absorption efficiency. The size of the tiny particles can be adjusted according to different breathing conditions, such as: Chronic Obstructive Pulmonary Disease (COPD), asthma, or depending on the liquid medication itself. Furthermore, it is important that patients receive the same dosage 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, that is to say, it can produce a specific range of mass median aerodynamic particle sizes in each operation ( MMAD, Mass Median Aerodynamic Diameter) and specific spray duration. In this way, drug waste and risks caused by excessive drug use can be reduced.

Referring to FIG. 1, an exemplary aerosolizer is mainly disclosed, which includes an upper shell 964, a lower shell 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 stressed by the relative displacement between the upper case 964 and the lower case 965. At the same time, a predetermined amount of liquid (not shown) medicament 50 is drawn from the storage container 961 to the nozzle 963 through the guide of the tube 966 to prepare for aerosolization. When the aerosolizer 90 is activated, the force generated by the unstressed biasing element 962 will push the quantitative liquid medicine 912 toward the nozzle 963 and pass it through the nozzle 963 to generate aerosol for the disease. Suffering from inhalation. For another exemplary aerosolizer and operation mechanism, refer to the disclosure of US Patent No. 5,964,416 (US Patent Application No. 08 / 726,219).

As shown in Fig. 1, the pressurized liquid medicine 912 moves along the way from point A to point A ', and at the same time moves from one high-pressure end to the other low-pressure end. In this way, the liquid medicine 912 is sucked out and pushed into the nozzle 963, and when the liquid medicine 912 passes through the nozzle 963, an aerosol is generated and the aerosol is simultaneously discharged. During aerosolization, it is important to maintain a proper seal between all components. Otherwise, the effect of aerosolization will be destroyed. For example, leakage from the nozzle 963 may cause pressure loss, resulting in inaccurate dose or improper aerosol particle size. Furthermore, the MMAD of the aerosol and the duration of the spray are affected. In order to avoid the above situation, it is necessary to maintain a high degree of attention and accuracy when manufacturing and assembling various components of the aerosolizer. However, because of the miniature size of these aerosolizer elements (which are typically on the order of millimeters or less), achieving a proper seal can be extremely difficult and costly. Furthermore, components with different geometries and micro-sizes may be more likely to be worn or torn under high pressure environments. The pressure of such high pressure environments is usually 5 to 50 million Pascals (MPa), that is, 50 to 500 bar. (Bar).

On the other hand, the nozzle 963 plays an important role, which atomizes the pressurized liquid medicine 912 into an aerosol of fine particles / droplets and ejects 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 guide of the connection tube. Generally speaking, the pressurized liquid medicine 912 flows into the nozzle 963 at a high speed, is filtered through the nozzle 963, and the flow rate is reduced in a controlled manner, so that a precise dose of the medicine can be aerosolized into a desired state. All of the above must be specially designed for the internal structure of the nozzle 963 to achieve results. Inappropriate design of the nozzle 963 may cause the complete aerosolization process to be hindered, shorten the life of the aerosolizer 90, or affect the accuracy of the dose.

A typical nozzle for an aerosolizer contains a plurality of elements with different geometries. For example, some components have a specific shape, such as an elongated protrusion that is used as a screening program. Some other elements have different shapes, such as the constituent elements of a guide system to control the flow of liquid in the nozzle. In short, nozzles in the related art require a combination and interaction of multiple elements with different structural and / or functional characteristics to achieve the desired atomization effect. However, as the size of the nozzles continues to shrink, fluid control therein has become increasingly difficult. The structure, size, and arrangement of the components in the nozzle need to be carefully designed and implemented to make the nozzle more efficient. Therefore, the cost of designing and manufacturing the nozzle is often high.

The main purpose of this patent application is to provide a nozzle structure, which has a less complicated structure, design and arrangement. The improved nozzle formed above can 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 microstructured path module for an aerosolizer. The passage module includes a plate body covered with an upper cover to form a cavity, and an inlet and an outlet through which liquid can flow. The plate body further includes a filtering structure. The filtering structure in the embodiment includes a protruding wall, a micro column, a protruding row, and a combination 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 channels. The protruding wall is along the flow direction, and the flow direction is substantially perpendicular to the inlet. In some embodiments, a plurality of micro-pillars protrude from the plate and are uniformly distributed in at least a part of the passage. However, in some embodiments, the configuration of the protruding wall may be continuous or discontinuous. A central column is located in the area near the outlet and occupies a considerable part of the area near the outlet, so that the liquid can only flow to the outlet through the longitudinal narrow channel. 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 track. 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 aerosolized agents to the patient's lungs. In order to achieve the above purpose, the MMAD of the aerosol must be less than 5.5 um, moreover, the MMAD must be between 4 and 5.5 um. In addition, when the aerosol is less than 5.5 um, the spray duration will more preferably be about 1.6 seconds. The above combination enhances the delivery of tiny particles to a specific area in the user's lungs, thus producing a more ideal treatment result. In some embodiments, the microstructured pathway module 1 and its constituent elements are specially designed and arranged, so the liquid medicine 912 with specific characteristics can be aerosolized and provided with a predetermined MMAD and spray duration . The composition of the liquid medicine 912 is a medicinal active ingredient, a stabilizer and a preservative. The medicinal active ingredient is selected from the group consisting of β-mimetics, inhibitors, anti-allergic agents, anti-histamines and / or steroids or combinations thereof. In addition, the liquid medicine 912 is a specific range that does not contain ethanol and has certain characteristics, 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 components described below can be composed of hardware (such as a circuit), or can be composed of hardware and software (such as writing a program to a processing unit). In addition, different components can be integrated into a single component, and a single component can also be separated into different components. Such changes should be within the scope of the invention.

The methods of making and using the disclosed embodiments are discussed in detail below. However, it should be understood that the following embodiments disclose many applicable inventive concepts, and that these inventive concepts can be expressed and covered using many different kinds of words. The specific methods used to make or use the embodiments disclosed below are merely examples, and do not limit the scope of other embodiments of the present invention.

Throughout the various perspectives and illustrated embodiments in this disclosure, similar reference numbers may be used to designate similar components. The following reference numbers are assigned in detail to the exemplified embodiments contained in the following figures. Wherever possible, the same reference numbers used in the illustrations and text descriptions are used to identify the same or similar elements. In each illustration, various shapes and thicknesses can be expressed in a slightly exaggerated manner to meet conditions such as clarity and easy identification. The following description will specifically point out some of the elements that form the device of the invention, or components that directly interact with the device of the invention. It is understood that components not specifically illustrated or described may take many different forms. In this disclosure, when referring to "an embodiment", it means that the 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 embodiments that are substantially referred to may not all refer to the same embodiment. 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 illustrations are not necessarily drawn according to actual scale, but are given priority for clarity and understanding. In the drawings, similar reference numbers are used to designate similar or similar elements, and the various illustrated embodiments of the present invention are thereby presented and described. The icons presented here do not all conform to their actual sizes, and for clarity of illustration, the icons may be exaggerated or simplified. Those with ordinary knowledge in the technical field to which the present invention pertains should be aware that various applications and changes derived from the various embodiments and illustrations 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 may mean that the component is placed directly above the other element, or that the element is located on the other element through another object. Above the component. However, if it is mentioned that one component is "directly above" another component, the above situation does not hold true through other objects.

It should be understood that unless there is a clear definition in this disclosure, even if the conditions of the "single" type are mentioned in the text, they can still be regarded as including the conditions of the "multiple" type. Moreover, related terms, such as "top" and "bottom", can be used herein to describe the relationship between a single element and other elements as shown in the figures.

It should be understood that when a description element is “under” other elements, it can also be interpreted as “above” the other element from different perspectives. The above term "under" may cover both "above" and "under".

It should be understood that the word "about" used in the text corresponds to the measurement value, such as: quantity, duration, aerosol measurement or the like, when the specific value covers ± 10% variation and more ± 5%, the variation can be regarded as a suitable variation that can achieve the desired purpose of cost disclosure.

Unless otherwise defined, each term (including technical and scientific terms) used in this disclosure has the same definition as understood by those having ordinary knowledge in the technical field to which this invention belongs. It is also understandable that the terms mentioned in this disclosure and also defined in commonly used dictionaries are to be interpreted in accordance with the cognition in the technical field to which the present invention belongs, and also consistent with those in this disclosure. The definitions are consistent; and unless defined directly here, these terms will not be interpreted in an ideal or overly formal way.

2 is a cross-sectional side view of an exemplary gas atomizer, which conforms to some embodiments described in this patent application. The gas atomizer 90 includes a housing 902, a pump chamber 904, and a spring chamber 906. The biasing element 9062 (eg, a spring) is coupled to the housing 902, and is more particularly mounted to the spring chamber 906. The spring chamber 906 also holds a storage container 908, where the storage container 908 can store a liquid medicament 912. The liquid medicament 912 may correspond to a preactuation of the aerosolizer 90 and is pulled out of the storage container 908 through the guide of the tube 910. In particular, the housing 902 may be rotated before the gas atomizer 90 is activated. The spring 9062 is urged by rotation of the housing 902. In contrast, the liquid medicine 912 is discharged from the storage container 908 to the pump chamber 904 and is ready to be atomized by gas. When the gas atomizer 90 is started, gas atomization is started. When the aerosolizer 90 is activated, the release mechanism (not shown) is triggered, and the spring 9062 is released from the stressed state to the unstressed state. The above operation generates a force, which pushes the liquid medicine 912 in the pump chamber 904 through the transmission device 950, which means that the microstructure access module 1 (ie, the nozzle) is located. That is, the liquid medicine 912 is aerosolized by passing through the microstructured path module 1. The micro-structured pathway module 1 is specially designed, so it is possible to manufacture aerosols with ideal particle size, and it is performed in a controlled and accurate manner. As a result, the aerosolized liquid medicament 912 will leave the transfer device 950 and be discharged out of the aerosolizer 90 for the patient to inhale. The liquid medicament of the examples includes a respirable composition. The liquid medicament may be a liquid solution as follows. In a more preferred embodiment, the liquid medicament is ethanol-free. More details of liquid medicaments will be described later. Moreover, in the preferred embodiment, the liquid pharmaceutical 912 is free of propellants (such as chlorofluorocarbon or hydrofluoroalkane propellants). Propellants are the source of propelled aerosols with drugs and are used in common pressure dose inhalers (MDI). However, propellants can have a negative effect on the environment. Therefore, it is more preferable that the gas atomizer 90 disclosed in the present invention can be operated without a propellant.

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

In order 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 5.5 um, and the spray duration is about 1.2 to 1.6 seconds. In a more preferred embodiment, the MMAD is between about 4-6 um, and the spray duration is about 1.2-1.6 seconds, and even more about 1.4-1.6 seconds. Aerosols with MMAD between about 4 and 6 um are suitable for inhalation treatment. Aerosols with MMAD above a certain range are more difficult to reach the patient's lungs, such as aerosols are more likely to deposit in the throat. On the other hand, aerosols with a MMAD below a specific range increase the spread of undesired aerosols, resulting in insufficient aerosols reaching the patient's lungs, which is ineffective treatment. And if the spray duration is not within a specific range, it will affect the patient's inhalation efficiency, increase the chance of clogging and residue, and affect the treatment. For example, an unsatisfactory effective spray time will result in a negative impact on the amount of aerosolized drug inhaled by the patient over a certain period of time. This patent application provides a microstructured pathway module capable of achieving the above-mentioned MMAD and spray duration. More conclusions will be detailed later.

FIGS. 3A to 3B are examples of the microstructured pathway module 1 and the microstructured pathway module 1, which conform to some embodiments described in this patent application.

FIG. 3A is a top view of the microstructured pathway module 1 and corresponds to some embodiments described in this patent application. Micro-structured access module 1 The micro-structured access module 1 includes an upper cover 20 and a plate body 10 (covered by the upper cover 20, not shown). The aforementioned combination forms a chamber to accommodate a filtering structure. Liquid (not shown) enters the chamber from the inlet 102 and is released at the outlet 104 in the form of an aerosol. The filtering structure ensures that the aerosol 50 has the above-mentioned characteristics and is suitable for human inhalation treatment. For example, the aerosol 50 having the above-mentioned MMAD and spray duration is disclosed herein.

FIG. 3B is a cross-sectional view of the microstructured pathway module 1 along the line XX ′ shown in FIG. 3A. In addition, the plate body 10 and the upper cover 20 form a cavity 202, and the cavity 202 includes a filtering structure (omitted to make the cavity more clear) to guide the direction of liquid flow or change the flow rate. The filtering structure may or may not be in contact with the plate body 10 and the upper cover 20. For example, the filtering structure may be a combination of the protruding rows 52, the micro-pillars 4, the protruding walls 5, and the protrusions from the plate body 10. With the filtering structure of this structure, the aerosolizer 50 has a specific MMAD and spray duration disclosed here.

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

Please refer to FIG. 4A, which discloses a microstructured path module 1. The micro-structured via module 1 includes a board 10, which can be made of silicon rubber 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 covers a glass upper cover 20 (not shown), with a width of about 2.5 mm, a length of about 2 mm, and a depth of about 675 um. The plate body 10 has a size corresponding to the upper cover 20 and forms a cavity. In addition, the plate body 10 and the upper cover 20 (not shown) are combined, and 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, and 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 aerosol 50 generated is from the outlet The 104 end leaves the chamber. The width of the inlet 102 is 2 mm, which is wider than the outlet 104. The liquid medicament 912 flows from the inlet 102 to the outlet 104 in a general direction in the chamber. The liquid medicine 912 is substantially perpendicular to the inlet 102 in the liquid flow direction in the passage module, and is defined as A-A '. At least a part of the liquid medicine 912 flows along the inclined wall 106 of the passage module 1, which causes the liquids to converge and collide with each other, or preferably the included angle of the confluence is about 90 °. Based on the above results, an aerosol 50 that can be inhaled by the patient is thus generated.

The plate body 10 further includes a central post 2, a spacer 3, a micro post 4, and a protruding wall 5. The micro-columns 4, the spacers 3, and the protruding walls 5 are arranged to form the filtering structure of the microstructure passage module 1. The spacers 3, the protruding walls 5, the micro-columns 4, and the central column 2 protrude in a direction transverse to the liquid flow. In some embodiments, the spacers 3 are arranged in multiple rows at the entrance 102, and the distance between two adjacent spacers 3 is twice the width of the passage 18. Each spacer block 3 has a rectangular cross-sectional shape, a width of about 50um, and a length of about 200um. In general, the spacer block 3 is used to preliminarily filter the liquid medicament 912 entering the chamber and divide it into separate channels 18.

In some embodiments, these components can be formed by etching the microstructured via module 1 to become a part of the plate body 10. In some embodiments, the etching depth of the plate body 10 is about 5 to 6 um to form the aforementioned partial elements in an integrated manner, and the depth thereof covers a manufacturing tolerance of 1 um. It is worth noting that the manufacturing method of the plate body 10 is not limited to this. The plate body 10 may be made by other methods known in the related art, such as: molding, welding or printing. Subsequent text will further describe other features and structures of the overall element.

Referring to FIG. 4B, the central pillar 2 protrudes from the plate body 10 and is close to the outlet 104. The shape of the central pillar 2 is approximately spherical, and its particle diameter is approximately 150 um. The central pillar 2 occupies a considerable portion of the area near the outlet 104, so that liquid can only flow to the outlet 104 through the two narrow channels 15 between the central pillar 2 and the inclined wall 106. The narrow track 15 extends continuously and longitudinally at least in part, in other words, part of the inclined wall 106 is parallel to the corresponding central pillar 2 area. The above structure will cause the liquid to flow in opposite directions, that is, along two opposite narrow channels 15. In other words, the microstructured pathway module 1 can be understood as including two outlets 104 for aerosolization. According to this, the opposite liquid jets ejecting the two narrow channels 15 meet at a position near the outlet 104 outside the passage module 1 and form an aerosol 50. The size of the central pillar 2 is such that the width W of each narrow track 15 is between approximately 6.7 and 8.3 um, and furthermore, the width W of the narrow track 15 is between approximately 7 and 8 um. It is worth noting that the manufacturing tolerance of the distance D and the width W is about ± 0.3 um. In a specific embodiment, the width W refers to the distance between the inclined wall 106 and the central pillar 2, and the measurement is shown in FIG. 4B.

4A and 4B, the plate body 10 further includes a protruding wall 5 disposed over the entire width of the plate body 10. The filtering structure of the present invention further includes this protruding wall 5 which is longitudinal and parallel to the liquid flow direction A-A ' . Between each parallel protruding wall 5 is a passage 18 through which the liquid medicine 912 can flow. The liquid flows in a plurality of paths 18 in a direction AA ′. The width of the passage 18 is about 77um, and the general width of the protruding wall 5 is about 22um.

In some embodiments, for the unfiltered liquid medicine 912 entering the microstructured pathway module 1, the space between the two protruding walls 5 is used as a screening program. For example, any particles larger than the width of the pathway 18 will be The space is blocked and filtered 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 protruding wall 5 is discontinuous. For example, a plurality of protruding rows 52 are arranged to form the protruding wall 5. In particular, there is a gap between two adjacent protruding rows 52, and the liquid flowing between the passages 18 flows laterally through the gap between the protruding rows 52. It is important that all the technical features disclosed in this patent application for the protruding wall 5 are applicable to continuous and discontinuous protruding walls 5. In other embodiments, only the micro-pillars 4 are used without providing the filtering function with the protruding walls 5.

As shown in FIGS. 4A to 4C, the micro-pillars 4 are circular and uniformly distributed. The above configuration forms a filtering structure 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-pillar 4 is a micron-sized component protruding from the plate body 10 and has a height of about 5-6 um. The distance between the microcolumns 4 is D, and the distance D is between about 6.7 ~ 8.3 um. More preferably, the distance D is between about 7 ~ 8 um. The distribution of the microcolumns 4 provides for filtering the liquid into fine particles, or increasing the flow resistance between the liquid medicines 912. Therefore, the flow rate of the liquid in the chamber is reduced. However, in some embodiments, the plate body 10 includes the protruding wall 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 junction of the side wall 108 and the inclined wall 106. In addition, the protruding wall 5 may be non-starting from the inlet 102. In one example, the protruding wall 5 starts from a distance from the inlet 102. The micropillar 4 occupies at least part of the passage 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. The term "occupancy" as used herein means that the micropillars 4 exist 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 region and a second region, and the first region is closer to the entrance 102 than the second region. In addition, in some embodiments, the passage 18 is located in the first region without the protruding wall 5 in the second region, and the micro-pillars 4 occupy at least the second region, and part, but not all of the first region.

The following will focus on Table I below, which provides droplet sizes, which are 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 this 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 a spray duration.

Table I

Table 1 reveals the measurement results (n = 3). The MMAD of the aerosol 50 is less than about 5.5um. Or preferably, the MMAD of the aerosol is between about 4-5um. In addition, the aerosol spray duration is less than 1.6 seconds. Or preferably, the spraying duration is between about 1.2 and 1.6 seconds. Or more preferably, the spray duration is between about 1.4 and 1.6 seconds. Correspondingly, the spray speed when the aerosol is sprayed on the outlet 104 is between about 169 and 175 m / s. Table 1 further provides a comparison of the fine particle fraction (FPF) of less than 5 microns in the pressurized liquid. 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 result, 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 W and the distance D is smaller than 8 um and / or the other of the width W and the distance D is larger than 7 um. The above structural design is beneficial for generating MMAD less than 5.5um and the spray duration is between about 1.5 and 1.6 seconds. As mentioned above, it is necessary to generate the ideal particle size and the mist used to deliver the lungs of patients with medicines.

In other words, the patient can inhale a fixed dose of the ideal particle size aerosol every time the aerosolizer 90 is operated. However, this patent application is not limited to the description in words, that is, any combination of the aforementioned width W and distance D appearing in the specific range of the aforementioned Table 1 falls into the scope of this patent application. In addition, as described above, the present disclosure is effective for generating aerosols with ideal MMAD and spray duration.

However, liquids with specific characteristics are related to the operation and ideal results of the gas atomizer 90. Specifically, the aerosolizer 90 transmits less than 20 ul of liquid with a pressure of at least 50 bar to generate a curative aerosol without propellant. In order to produce effective results, aerosols must have the characteristics disclosed herein. To achieve this, the liquid itself and its environment must be controlled.

In a specific embodiment, 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 medicinal active ingredient is selected from beta-mimetics, anticholinergics, antiallergics, antihistamines, and / or steroids or a combination thereof. For example, the medicinal active ingredient may be selected from the group consisting of Albuterol Sulfate, Ipratropium Bromide, Tiotropium, Olodaterol, and Budesonide. , Formoterol, Fenoterol, etc. The ideal concentration of active ingredients in the solution is 0.001 ~ 2g / 100 ml. A suitable stabilizer may be ethylenediamine tetraacetic acid (EDTA) at a concentration of 0.001 to 1 mg / ml in the solution, specifically, the concentration is less than about 0.5 mg / ml, and more preferably, the concentration is less than About 0.25 mg / ml. A suitable preservative may be Benzalkonium Chloride. In addition, the pH of the solution composition needs to be adjusted to a specific range, so the solution composition may include citric acid and hydrochloric acid. In a specific preferred embodiment, the composition of the liquid may be 0.22 to 023 mg / ml of Tiotropium Bromide or its analog, 0.08 to 0.12 mg / ml of Benzalkonium or its analog And 0.08 ~ 0.12 mg / ml of EDTA or its analog. In addition, the pH 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. In addition, in a specific preferred embodiment, the liquid has a low viscosity (viscosity), about 0.88 cP at room temperature, and the surface tension of the liquid is about 43-48 dyne. In other embodiments, the liquid is aerosolized to form a propellant-free aerosol for application to a patient's lungs.

As shown in FIG. 2, the liquid is stored in a storage container 908 and then transferred to an aerosolizer 90. It is important that the liquid system does not contain any inappropriate ingredients or pharmaceutical properties, causing damage or reaction to the aerosolizer 90 or storage container 908. For example, the liquid may be a non-ethanol solution, and thus may be stably stored in a container. Further, the effective amount of the medicinal active ingredient and the stabilizer with an ideal concentration can prevent the device from being damaged or corroded. For example, if EDTA is used, its concentration in the solution composition needs to be optimized. High-concentration EDTA will increase the solution channel of the nozzle Opportunities to form crystals, which can lead to blockages or obstructions.

In addition to the above, the design combination of the specific structure of the microstructure pathway module 1 and the choice of the liquid composition make the aerosolizer 90 generate aerosol and spray duration with a predetermined MMAD in a wider temperature range . Next, the following will discuss the following two.

Table II

Table 2 shows the effects of the specially structured microstructured pathway module 1 in this disclosure at different operating temperatures. It can be known from the above that the gas atomizer (n = 3) can be operated at an operating temperature of about 4-25 degrees Celsius. In one example, the storage container containing the medicament is stored in a refrigerator, and the storage container is placed at a temperature of 4 degrees Celsius before operation. As shown in Table 2, the microstructured path module 1 in the present disclosure can generate aerosols with similar characteristics between 4 and 25 degrees Celsius. In other words, the microstructure pathway module 1 of this special configuration in the present disclosure can generate an ideal aerosol under severe environments. Patients benefit from aerosol inhalation treatments that can operate in more diverse environments. In addition, within this operating temperature range, the aerosolizer becomes more suitable for liquid medicaments with specific liquid viscosities. In some embodiments, the viscosity of the medicament solution is adjusted to about 0.5 to 3 cP. In the embodiment, 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 spray duration, so it is best to keep the viscosity low. In addition, the structure of the microstructure pathway module 1 in this disclosure makes it more suitable for liquid pharmaceuticals with a specific surface tension. In some embodiments, the surface tension of the liquid pharmaceuticals ranges from about 20 to 70. mN / m, or more preferably, between about 25 and 50 mN / m. The lower surface tension can provide better diffusion ability of the agent, therefore increasing the deposition of aerosol on the lung surface, improving the effectiveness of the agent and inhalation treatment.

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

In other words, this disclosure is a microstructured pathway module 1 that is specially configured to produce ideal aerosols in severe environments. Patients benefit a lot because their aerosol inhalation treatment can Operating in the environment.

In summary, the micro-structured via module 1 provided in this disclosure is easier to manufacture due to the reduced complexity of the structure and its micro-sized components. The finished device can deliver a more precise dose of aerosol with ideal MMAD and spray duration each time the aerosolizer is operated.

Among them, the reference signs are described as follows:

1‧‧‧Microstructure access module

2‧‧‧ central column

3‧‧‧ spacer

4‧‧‧ microcolumn

10‧‧‧ plate

102‧‧‧ Entrance

104‧‧‧Export

106‧‧‧ inclined wall

108‧‧‧ sidewall

15‧‧‧Narrow Road

18‧‧‧ access

50‧‧‧ aerosol

912‧‧‧Liquid Pharmacy

52‧‧‧ protruding row

5‧‧‧ protruding wall

90‧‧‧Atomizer

20‧‧‧ Upper cover

902‧‧‧shell

904‧‧‧pump room

906‧‧‧Spring Room

9062, 962‧‧‧ bias components

9062‧‧‧Spring

908, 961‧‧‧ storage container

910, 966‧‧‧ tube

950‧‧‧ transmission device

963‧‧‧Nozzle

964‧‧‧ Upper shell

965‧‧‧ Lower shell

A-A’‧‧‧ direction of liquid flow

The drawings depict one or more embodiments by way of example and not limitation, where elements having the same reference digit identification number always represent similar elements. The drawings are not to scale unless otherwise disclosed.

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

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

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

4A, 4B, and 4C illustrate side cross-sectional views of a series of microstructured pathway 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 patent application of the present invention. In these illustrations, the size of each part may not necessarily match the actual size for the sake of clarity. The reference signs used in the claims are not intended to limit the scope of the present invention. For example, the same or similar element numbers are used in different drawings.

Claims (20)

A microstructure access module applied to an aerosolizer, comprising: a plate body covered with an upper cover to form a cavity; and an entrance of the cavity defined by the combination of the plate body and the upper cover. And outlet, the direction in which liquid flows 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 across the entire width of the plate body, The plurality of protrusion walls are defined as a plurality of channels; a plurality of micro-pillars are formed protruding from the plate body, and the distance between adjacent ones is defined as D; a central column is protruded from the plate body, close to and Mostly occupy the outlet, forming a narrow channel between the central pillar and the outlet for the liquid to flow through, and the narrow channel width is W; wherein the liquid flows along the liquid Flowing through the chamber in a direction to generate an aerosol of a predetermined mass median aerodynamic particle size (MMAD); wherein the width W is between 6.7 and 8.3 um and the distance D is between 6.7 and 8.3 um. The microstructured path module according to claim 1, wherein at least one of the width W or the distance D is less than 8 um. The microstructured path module according to claim 2, wherein at least one of the width W or the distance D is greater than 7 um. The microstructured path module according to claim 1, wherein the predetermined MMAD is less than 5.5 um. The microstructure access module according to claim 1, wherein the gas atomizer further has a spray duration of 1.2 to 1.6 seconds. The microstructured pathway module according to claim 1, wherein a proportion of the droplet size of the aerosol smaller than 5 microns is less than 50%. The microstructured pathway module according to claim 1, wherein the proportion of the droplet size of the aerosol smaller than 5 microns is between 35 and 45%. The microstructure via module according to claim 1, wherein a cross-section of the micro-pillar is circular. The microstructure pathway module according to claim 8, wherein the microcolumns are uniformly distributed. The microstructured pathway module according to claim 1, wherein the liquid system does not contain ethanol. The microstructured pathway module according to claim 1, wherein the viscosity of the liquid is between 0.5 and 3 cP. A microstructure access module applied to the aerosolizer 90, comprising: a plate body covered with an upper cover to form a cavity; and a cavity of the cavity defined by the combination of the plate body and the upper cover. An inlet and an outlet; a filtering structure provided on the plate body; and a central pillar protrudingly formed from the plate body, occupying the outlet near and mostly, forming a narrow path between the central pillar and the Between the outlets 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 filtering structure increases the liquid's Flow resistance produces aerosols with MMAD (mass median aerodynamic particle size) less than 5.5um; wherein the width W is between 6.7 and 8.3 um; and wherein the liquid contains medicinal active ingredients, stabilizers and preservatives . The microstructured path module according to claim 12, wherein the width W is between 7 and 8 um. The microstructured pathway module according to claim 12, wherein the liquid system does not contain ethanol. The microstructured path module according to claim 12, wherein its operating temperature is lower than 25 degrees Celsius. The microstructured pathway module according to claim 12, wherein the viscosity of the liquid is less than 3 cP. The microstructured pathway module according to claim 16, wherein the viscosity of the liquid is between 0.8 and 1.6 cP. The microstructure pathway module according to claim 12, wherein the medicinal active ingredient is selected from the group consisting of β-mimetics, inhibitors, antiallergic agents, antihistamines, or combinations thereof. The microstructured pathway module according to claim 18, wherein the stabilizer is EDTA and its concentration is lower than 0.25 mg / ml. The microstructured access module according to claim 12, wherein the liquid is aerosolized to form a propellant-free aerosol for application to a patient's lungs.