Use of bacterial cellulose for treating or preventing airway diseases

Abstract

The invention discloses application of bacterial cellulose to treatment or prevention of airway diseases, in particular to application to treatment or prevention of inflammatory airway diseases related to airway epithelial cell damage, such as asthma.

Description

TECHNICAL FIELD

[0001] The present invention relates to the use of bacterial cellulose in treating or preventing airway diseases, in particular, the use of bacterial cellulose in treating or preventing inflammatory airway diseases exacerbated by airway epithelial cell damage. BACKGROUND

[0002] Asthma is a chronic airway disease characterized by airway inflammation, airway hyperresponsiveness, and increased mucus secretion. Airway epithelial cells play an important role in the pathogenesis of asthma. It is known that when environmental allergens or pathogens contact epithelial cells, epithelial cells produce and release a large amount of inflammatory factors (IL-25, IL-33, TSLP, etc.), and the release of these epithelial inflammatory factors (also known as alarmins) can activate a large number of immune cells such as Th2 and ILC2 cells, ultimately leading to eosinophilic airway inflammation, and can also directly activate mast cells to cause airway inflammation and airway hyperresponsiveness.

[0003] Epithelial cell damage can be found in all phenotypes of asthma. The airway epithelial cells of asthma patients are damaged, characterized by epithelial cell detachment, reduced expression of intercellular adhesion molecules such as tight junction proteins (ZO-1, Claudins, occludin, TJP2) and adherent junction proteins (β-catenin and E-cadherin), resulting in impaired barrier function and increased permeability to external pathogens and allergens. On the other hand, the decrease in the expression of intercellular adhesion molecules and adherent junction proteins in damaged epithelial cells increases the likelihood of epithelial-to-mesenchymal transition (EMT) of airway epithelial cells, exacerbating airway remodeling in asthma patients, thereby leading to exacerbation of asthma.

[0004] The aforementioned pathogenesis of epithelial cell damage and impaired barrier function also widely occurs in other airway diseases. However, current treatments for airway diseases are not aimed at repairing epithelial cell damage, and there is no effect on repairing damaged epithelial cells, so airway diseases cannot be treated comprehensively, and when environmental allergens or pathogens re-contact epithelial cells, airway diseases recur.

[0005] In the past decade, the rapid development of nanotechnology has inspired the creation of a variety of materials with great therapeutic potential. Many functional nanomaterials with anti-inflammatory and antioxidant effects have been developed, such as metal oxide nanoparticles (NPs), carbon nanomaterials, and noble metal NPs, which have been reported to be used for the treatment of diseases, including stroke, sepsis, inflammatory bowel disease, neurodegenerative disease, diabetes, acute kidney injury, and acute liver injury.

[0006] In addition, cellulose, as the most abundant natural polymer material on earth, is also one of the nanomaterials that have attracted attention. In recent years, a highly crystalline linear glucose biopolymer, bacterial cellulose (BC), produced by bacterial fermentation, has attracted more attention. BC has unique physical and chemical properties, such as high elastic modulus, high specific surface area, low density, non-abrasiveness, easy surface functionalization, high chemical composition purity, high crystallinity, high polymerization degree (2000-8000), good biocompatibility, and good biodegradability. Bacterial cellulose has been applied in wound dressings, vascular tissue engineering, and bone tissue regeneration, and has been proven to have good biocompatibility.

[0007] However, the application of nanomaterials in airway diseases is still very rare. Due to the special anatomical structure and immune environment of the lungs, it is of great significance to develop nanomaterials with smaller particle size, more uniform, better in vivo stability, more mild composition, and better biocompatibility. SUMMARY

[0008] In view of the various deficiencies of the prior art described above, the present application provides a use of a composition for the preparation of a medicament for treating or preventing airway diseases, wherein the composition comprises bacterial cellulose formed by β-1-4-glucan, and the bacterial cellulose has a diameter of 15 nm to 35 nm and a length of 100 nm to 3000 nm.

[0009] In a specific embodiment, the aspect ratio of the bacterial cellulose is 2.5 to 86.

[0010] In a specific embodiment, the content of the bacterial cellulose in the composition is 0.2% to 1.2% by weight.

[0011] In a specific embodiment, the composition is administered to an individual in need thereof at a dose of 1 to 4 times a day, and the dose of the composition administered each time is 0.1 mg to 0.5 mg of the bacterial cellulose per kg of body weight.

[0012] In a specific embodiment, the composition is administered to the individual intranasally or by inhalation, preferably, the intranasal administration includes in the form of drops or sprays, and the inhalation administration includes in the form of an atomizer or a dry powder.

[0013] In a specific embodiment, the composition further comprises a carrier, and the bacterial cellulose is dispersed in the carrier, and the carrier is selected from water, physiological saline, buffer, and Ringer's solution.

[0014] In a specific embodiment, the composition further comprises at least one selected from the group consisting of flavoring agents, dispersants, wetting agents, lubricants, thickening agents, stabilizers, preservatives, antioxidants, antibacterial agents, and coloring agents.

[0015] In one embodiment, the bacterial cellulose is formed by at least one bacterium selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, and Agrobacterium; preferably, the bacterial cellulose is formed by a bacterium of the genus Gluconacetobacter and / or Acetobacter.

[0016] In one embodiment, the airway disease is selected from asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, bronchitis, allergic rhinitis, chronic cough, and alveolitis; preferably, the airway disease is asthma.

[0017] The present application also provides a method of treating or preventing an airway disease, wherein the method comprises administering to an individual in need thereof a therapeutically effective amount of a composition comprising bacterial cellulose formed of β-1-4-glucan, and the bacterial cellulose has a diameter of 15 nm to 35 nm and a length of 100 nm to 3000 nm.

[0018] In one embodiment, the aspect ratio of the bacterial cellulose is 2.5 to 86.

[0019] In one embodiment, the content of the bacterial cellulose in the composition is 0.2 wt% to 1.2 wt%.

[0020] In one embodiment, the composition is administered to the individual in a dose of 1 to 4 times a day, and the dose of the composition administered each time is 0.1 mg to 0.5 mg of the bacterial cellulose per kg of body weight.

[0021] In one embodiment, the composition is administered to the individual nasally or by inhalation, preferably, the nasal administration comprises in the form of nasal drops or nasal spray, and the inhalation administration comprises in the form of a nebulizer or dry powder.

[0022] In one embodiment, the composition further comprises a carrier in which the bacterial cellulose is dispersed, and the carrier is selected from water, physiological saline, buffer, and Ringer's solution.

[0023] In a specific embodiment, the composition further comprises at least one selected from the group consisting of flavoring agents, dispersing agents, wetting agents, lubricants, thickening agents, stabilizing agents, preservatives, antioxidants, antibacterial agents, and coloring agents.

[0024] In a specific embodiment, the bacterial cellulose is formed by at least one bacteria selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, and Agrobacterium; preferably, the bacterial cellulose is formed by bacteria of the genus Gluconacetobacter and / or Acetobacter.

[0025] In a specific embodiment, the airway disease is selected from asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, bronchitis, allergic rhinitis, chronic cough, and alveolitis; preferably, the airway disease is asthma.

[0026] The present application also provides a composition comprising bacterial cellulose formed of β-1-4-glucan for use in the treatment or prevention of an airway disease, wherein the bacterial cellulose has a diameter of 15 nm to 35 nm and a length of 100 nm to 3000 nm.

[0027] In a specific embodiment, the aspect ratio of the bacterial cellulose is 2.5 to 86.

[0028] In a specific embodiment, the content of the bacterial cellulose in the composition is 0.2 wt% to 1.2 wt%.

[0029] In a specific embodiment, the composition is administered to a subject in need thereof in a dose of 1 to 4 times a day, and the dose of the composition administered each time is 0.1 mg to 0.5 mg of the bacterial cellulose per kg of body weight.

[0030] In a specific embodiment, the composition is administered to the subject nasally or by inhalation; preferably, the nasal administration comprises in the form of nasal drops or nasal spray, and the inhalation administration comprises in the form of a nebulizer or dry powder.

[0031] In a specific embodiment, the composition further comprises a carrier in which the bacterial cellulose is dispersed, and the carrier is selected from water, physiological saline, buffer, and Ringer's solution.

[0032] In one specific embodiment, the composition further comprises at least one of the group consisting of flavoring agents, dispersants, wetting agents, lubricants, thickeners, stabilizers, preservatives, antioxidants, antibacterial agents, and coloring agents.

[0033] In one specific embodiment, the bacterial cellulose is formed by at least one bacterium selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, and Agrobacterium; preferably, the bacterial cellulose is formed by bacteria of the genus Gluconacetobacter and / or Acetobacter.

[0034] In one specific implementation scheme, the airway disease is selected from asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, bronchitis, rhinitis, chronic cough, and alveolitis; preferably, the airway disease is asthma.

[0035] Specifically, the bacterial cellulose used in this invention has good biocompatibility in the lungs and plays a role in maintaining the homeostasis of the airway epithelial barrier, indicating that the use of bacterial cellulose in the lungs is feasible. It can effectively repair the damaged epithelial barrier function in airway diseases such as asthma and reduce inflammatory symptoms, thus making up for the current shortcomings in the treatment of airway diseases. Attached Figure Description

[0036] Figure 1 shows the results of animal toxicity tests on the bacterial cellulose of the present invention, wherein... FIG. 1A Dosage regimens demonstrating toxicity testing; FIG. 1B The results showed no statistically significant difference in body weight changes among the groups of mice during the toxicity experiment; FIG. 1C The images show the staining (H&E and PAS) of lung tissue pathological sections from each group of mice.

[0037] Figure 2 shows the experimental results of using the bacterial cellulose of the present invention to reduce airway damage and inflammatory response in an animal asthma model. FIG. 2A This shows the dosing regimen used to induce a mouse asthma model with HDM; FIG. 2B The images show the staining (H&E and PAS) of lung tissue pathological sections from each group of mice. FIGS. 2C to 2G The levels of the inflammatory factor IL-13 in the bronchoalveolar lavage fluid (BALF) of mice in each group were displayed separately. FIG. 2C ), IL-5 FIG. 2D ), IL-25FIG. 2E ), IL-33 FIG. 2F ) and TSLP FIG. 2G ) performance graph; FIG. 2H Immunofluorescence staining images of tight junction protein (ZO-1) and adhesion junction proteins (β-catenin and E-cadherin) in lung epithelial cells of mice in each group are shown, with a scale bar of 50 μm. FIG. 2I The display will FIG. 2H Histograms were obtained after quantification of immunofluorescence staining patterns. For each group of ZO-1, β-catenin, and E-cadherin, data are shown from left to right for the control group, HDM group, HDM+2 mg / kg BC group, and HDM+4 mg / kg BC group, respectively. Values ​​are expressed as mean ± standard deviation. Analysis was performed using one-way ANOVA and Tukey's multiple range test. * indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001, and ns indicates no significant difference.

[0038] Figure 3 shows the experimental results of using bacterial cellulose of the present invention to reduce airway damage in a cellular asthma model. FIG. 3A The results of the CCK8 cytotoxicity assay are shown in the figure. FIG. 3B This figure shows the effects of different concentrations of bacterial cellulose, tested by Western blotting, on the expression levels of β-catenin and E-cadherin in an HDM-induced asthma cell model. The figure below shows the quantified results, with data for each group of E-cadherin and β-catenin, from left to right: control group, HDM group, 0.4 g / ml group, 0.8 g / ml group, 1.6 g / ml group, and 3.2 g / ml group. FIG. 3C Immunofluorescence staining images of tight junction protein (ZO-1) and adhesion junction protein (E-cadherin) in cells of each group are shown. Analysis was performed using one-way ANOVA and Tukey's multiple range test, where * indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001, and ns indicates no significant difference.

[0039] FIG. 4 and FIG. 5 These are electron microscope images of bacterial cellulose from the present invention, wherein, FIG. 4 The bacterial cellulose of the present invention is shown to be uniform in size and well dispersed, without any entanglement or aggregation. FIG. 5 The dimensions of the bacterial cellulose of the present invention are further shown, having a diameter of 15 nanometers to 35 nanometers and a length of 100 nanometers to 3000 nanometers. Detailed Implementation

[0040] The following specific embodiments illustrate the implementation of this disclosure. Those skilled in the art can easily understand the advantages and effects of this disclosure from the content described in this specification. This disclosure can also be implemented or applied through other different embodiments, and the details in this specification can also be modified and changed based on different viewpoints and applications without departing from the spirit described in this disclosure.

[0041] In this disclosure, the terms "comprising," "including," or "having" a specific element may, unless otherwise stated, include other components, parts, structures, regions, locations, devices, systems, steps, or connections, rather than excluding such other elements.

[0042] Unless otherwise expressly stated in this disclosure, the singular forms “a” and “the” used in this disclosure also include the plural forms, and the terms “or” and “and / or” used in this disclosure are interchangeable.

[0043] The numerical ranges described in this disclosure are inclusive and can be combined. Any value falling within the numerical ranges described in this disclosure can be used as a maximum or minimum value to derive a secondary range. For example, the numerical range of "diameter of 15 to 35 nanometers" should be understood to include any secondary range between a minimum of 15 nanometers and a maximum of 35 nanometers, such as: 15 nanometers to 30 nanometers, 16 nanometers to 35 nanometers, and 22 nanometers to 28 nanometers, etc. Furthermore, if a value falls within any of the ranges described in this disclosure (such as between the maximum and minimum values), it should be considered as included within the range of this disclosure.

[0044] The bacterial cellulose disclosed herein refers to cellulose produced by bacteria, such as through bacterial fermentation, which is composed of D-glucose molecules linked together by β(1→4) glycosidic bonds and belongs to the β-1-4-glucan family. Unlike plant cellulose, bacterial cellulose has a higher purity.

[0045] In one specific embodiment, the bacterial cellulose has a diameter of 15 nanometers to 35 nanometers, such as about 15 nanometers, about 16 nanometers, about 17 nanometers, about 18 nanometers, about 19 nanometers, about 20 nanometers, about 21 nanometers, about 22 nanometers, about 23 nanometers, about 24 nanometers, about 25 nanometers, about 26 nanometers, about 27 nanometers, about 28 nanometers, about 29 nanometers, about 30 nanometers, about 31 nanometers, about 32 nanometers, about 33 nanometers, about 34 nanometers, or about 35 nanometers. In some specific embodiments, bacterial cellulose has a length of 100 nanometers to 3000 nanometers, for example, about 100 nanometers, about 150 nanometers, about 200 nanometers, about 250 nanometers, about 300 nanometers, about 350 nanometers, about 400 nanometers, about 450 nanometers, about 500 nanometers, about 550 nanometers, about 600 nanometers, about 650 nanometers, about 700 nanometers, about 750 nanometers, about 800 nanometers, about 850 nanometers, about 900 nanometers, about 950 nanometers, about 1000 nanometers, about 1050 nanometers, about 1100 nanometers, about 1150 nanometers, about 1200 nanometers, about 1250 nanometers, about 1300 nanometers, about 1350 nanometers, about 1400 nanometers, about 1450 nanometers, and about 1500 nanometers. 0 nm, approximately 1550 nm, approximately 1600 nm, approximately 1650 nm, approximately 1700 nm, approximately 1750 nm, approximately 1800 nm, approximately 1850 nm, approximately 1900 nm, approximately 1950 nm, approximately 2000 nm, approximately 2050 nm, approximately 2100 nm, approximately 2150 nm, approximately 2200 nm, approximately 2250 nm, approximately 2300 nm, approximately 2350 nm, approximately 2400 nm, approximately 2450 nm, approximately 2500 nm, approximately 2550 nm, approximately 2600 nm, approximately 2650 nm, approximately 2700 nm, approximately 2750 nm, approximately 2800 nm, approximately 2850 nm, approximately 2900 nm, approximately 2950 nm, or approximately 3000 nm. In some specific embodiments of this disclosure, diameter refers to average diameter and length refers to average length, i.e., the average diameter of bacterial cellulose is between 15 nanometers and 35 nanometers, and the average length is between 100 nanometers and 3000 nanometers. In at least one specific embodiment of this disclosure, the diameter of bacterial cellulose is preferably between 15 nanometers and 25 nanometers, and the length is preferably between 100 nanometers and 1000 nanometers, more preferably between 200 nanometers and 650 nanometers. In one specific embodiment, the aspect ratio of the bacterial cellulose is from 2.5 to 86, for example, about 2.5, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 86.

[0046] In this disclosure, bacterial cellulose formed from β-1-4-glucan has the use of preparing compositions for treating or preventing airway diseases, including administering bacterial cellulose formed from β-1-4-glucan to an individual in need. In some embodiments, the compositions of this disclosure may be pharmaceutical compositions, but are not limited thereto. In some embodiments of this disclosure, the airway disease may be asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, bronchitis, rhinitis, chronic cough, or alveolitis; preferably, the airway disease treated or prevented by this disclosure is asthma. The compositions of this disclosure can effectively treat or prevent airway diseases, or prevent the worsening of airway diseases.

[0047] In one specific embodiment, an individual requiring treatment or prevention of airway disease may administer bacterial cellulose or a combination thereof formed from β-1-4-glucan directly via the nasal cavity, for example, in the form of drops or sprays, and is not limited thereto. In another specific embodiment, an individual requiring treatment or prevention of airway disease may inhale bacterial cellulose or a combination thereof formed from β-1-4-glucan directly, for example, through oral or nasal inhalation, or, for example, in the form of a nebulizer or dry powder, and is not limited thereto.

[0048] In one specific embodiment, the bacterial cellulose formed from β-1-4-glucan or a composition containing thereof may be dried before use, for example, by freeze-drying to form dried block-shaped lyophilized tablets, or dry powder, or by further processing the dry powder into tablets. In some specific embodiments of this disclosure, the bacterial cellulose or a composition containing thereof may be subjected to at least one of the following processes: low-temperature freezing, low-temperature low-pressure degassing, and desorption, to improve the stability of the overall product and reduce its susceptibility to deterioration, thus facilitating storage. In use, due to the excellent rehydration properties of bacterial cellulose fibers, the dried product (e.g., lyophilized tablets, dry powder, or tablets) is easily mixed with a liquid carrier, thus making it a composition comprising a liquid carrier and bacterial cellulose. In some specific embodiments of this disclosure, the bacterial cellulose or a composition containing thereof may be processed sequentially by low-temperature freezing, low-temperature low-pressure degassing, and desorption; however, it should be understood that the order of the processing procedures is not limited thereto and may be appropriately adjusted according to the desired characteristics of the bacterial cellulose.

[0049] In some specific embodiments, the compositions of this disclosure can be formulated into dosage forms commonly used for airway diseases, facilitating self-administration by an individual or administration by another person to an individual. In some specific embodiments of this disclosure, the dosage form is, for example, a nasal drop or spray, or an inhaled nebulizer or dry powder. Besides dry powder, other dosage forms such as drops, sprays, and nebulizers may include a liquid carrier, which may include, but is not limited to, non-irritating liquids such as water, saline, buffer solutions, and Ringer's solution. When provided to an individual in the form of drops, sprays, or nebulizers, because the composition contains a liquid carrier, it is not necessary to pre-mix the bacterial cellulose and liquid carrier prepared according to this disclosure before using the compositions of this disclosure.

[0050] In some embodiments of this disclosure, the bacterial cellulose content, based on the total weight of the composition, may be between 0.2 wt% and 1.2 wt% to increase its dispersion rate. For example, the fiber content may be about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1.0 wt%, about 1.1 wt%, or about 1.2 wt%. In some embodiments of this disclosure, when the fiber content is below 0.2 wt%, the fibers may not provide sufficient hydroxyl groups, thus affecting the interfacial tension of the liquid medium to some extent. In some embodiments of this disclosure, when the fiber content is below 0.2 wt%, the liquid medium and fibers may aggregate due to cohesive forces, resulting in stratification and hindering mixing.

[0051] In some specific embodiments, the bacteria used to produce bacterial cellulose may be at least one selected from the genera *Gluconacetobacter*, *Acetobacter*, *Rhizobium*, *Sarcina*, *Pseudomonas*, *Achromobacter*, *Alcaligenes*, *Enterobacter*, *Azotobacter*, *Agrobacterium*, or any combination thereof. In some specific embodiments, the bacteria may be selected from the genera *Gluconacetobacter* and / or *Acetobacter*. In some specific embodiments, the bacteria disclosed herein may be at least one bacterium selected from the group consisting of *Acetobacter xylinum* (or *Gluconacetobacter xylinus*), *Gluconacetobacter hansenii*, and *Gluconacetobacter sacchari*. In some specific embodiments of this disclosure, strains of the genus *Acetobacter*, particularly *Acetobacter xylinum*, may be selected for the production of bacterial cellulose, but are not limited thereto. In some specific embodiments of this disclosure, a single strain or multiple strains may be selected for the production of bacterial cellulose, and this selection can be adjusted without limitation according to actual needs.

[0052] To prepare the bacterial cellulose of this disclosure, a container filled with culture medium is first prepared, and the aforementioned single or multiple bacterial strains are statically cultured in the container for 24 to 96 hours (e.g., 24, 36, 48, 60, 72, 84, or 96 hours). The absorbance (wavelength at 620 nm) of the bacterial concentration in the culture medium is controlled within the range of 0.005 to 0.01, for example, about 0.005, about 0.006, about 0.007, or about 0.00. 8. Approximately 0.009 or approximately 0.01; In some specific embodiments of this disclosure, the pH of the culture medium is controlled in an acidic environment, including pH values ​​between 0.5 and 6.5, such as approximately 0.5, approximately 1.0, approximately 1.5, approximately 2.0, approximately 2.5, approximately 3.0, approximately 3.5, approximately 4.0, approximately 4.5, approximately 5.0, approximately 5.5, approximately 6.0, or approximately 6.5; In some specific embodiments of this disclosure, the concentration range of bacteria in the culture medium is controlled within 10... 2 Up to 10 5 Cells / ml, e.g., approximately 1×10 2 Cells / ml, approximately 5 × 10 2 Cells / ml, approximately 1×10 3Cells / ml, approximately 5 × 10 3 Cells / ml, approximately 1×10 4 Cells / ml, approximately 5 × 10 4 Cells / ml or approximately 1×10 5 The bacterial concentration per milliliter; in some specific embodiments of this disclosure, the culture temperature can be controlled between 25°C and 30°C, such as about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, or about 30°C. In some specific embodiments of this disclosure, the absorbance value of the bacterial concentration in the aforementioned culture medium, the pH value of the culture medium, the concentration range of the bacteria in the culture medium, the culture temperature, or any combination thereof can be selected to control the culture of the bacteria of this disclosure.

[0053] As used in this disclosure, "static culture" refers to the formation of a layered fibrous membrane by bacteria in a nonwoven manner on the surface of the culture medium (i.e., the gas-liquid interface). Furthermore, the container used for static culture can be a flat container with a wide culture area, allowing for control of bacterial oxygen consumption through a lower container height, thereby regulating the diameter of the bacterial cellulose. In some specific embodiments of this disclosure, because the network structure formed by the fibers on the surface of the synthetic fibrous membrane has a greater density and is more compact than the network structure inside the fibrous membrane, the aforementioned static culture and culture conditions facilitate subsequent separation of the interwoven bacterial cellulose.

[0054] As used in this disclosure, a "fiber membrane" refers to a layered material composed of multiple interwoven fibers and having a multilayered network structure. In some embodiments of this disclosure, the thickness of the fiber membrane may be between 20 micrometers and 30 micrometers, such as about 20 micrometers, about 22 micrometers, about 24 micrometers, about 25 micrometers, about 26 micrometers, about 28 micrometers, or about 30 micrometers. In some embodiments of this disclosure, the amount of bacterial cellulose per unit area of ​​the fiber membrane is between 0.001 g / cm² and 0.002 g / cm², such as about 0.0011 g / cm², about 0.0012 g / cm², about 0.0013 g / cm², about 0.0015 g / cm², about 0.0017 g / cm², about 0.0018 g / cm², or about 0.0019 g / cm². In some specific embodiments of this disclosure, the diameter of bacterial cellulose in the fiber membrane is between 15 nanometers and 100 nanometers, such as about 15 nanometers, about 20 nanometers, about 25 nanometers, about 30 nanometers, about 35 nanometers, about 40 nanometers, about 45 nanometers, about 50 nanometers, about 55 nanometers, about 60 nanometers, about 65 nanometers, about 70 nanometers, about 75 nanometers, about 80 nanometers, about 85 nanometers, about 90 nanometers, about 95 nanometers, or 100 nanometers.

[0055] In at least one specific embodiment, the components of the culture medium may include: a carbon source, a nitrogen source, and a gel support, wherein the carbon source may include at least one sugar or sugar alcohol such as mannitol, glucose, or molasses; the nitrogen source may include peptone, yeast extract, or a combination thereof; and the gel support may be selected from, but is not limited to, agar. In some specific embodiments of this disclosure, the culture medium may include agar, a carbon source, peptone, and yeast extract, wherein the weight ratio of the carbon source, peptone, and yeast extract may be from 5:1:1 to 4:1:1.

[0056] In at least one specific embodiment of this disclosure, the fiber membrane can be prepared by static fermentation of bacteria of the genus *Gluconobacterium* in a culture medium including mannitol, peptone, yeast extract and agar, wherein the resulting fiber membrane has a water content greater than 85%, such as greater than 90%, greater than 92% or greater than 95%.

[0057] In at least one embodiment, the bacterial cellulose of this disclosure is obtained by processing a fibrous membrane after bacterial fermentation culture. To obtain bacterial cellulose, processing the fibrous membrane includes subjecting it to a fiber-splitting process, which includes at least one of the group consisting of homogenization, swelling, and mechanical grinding. In at least one embodiment, the fiber-splitting process includes, but is not limited to, the sequential execution of homogenization, swelling, and mechanical grinding.

[0058] As used in this disclosure, "homogenization and pulverization" refers to mixing a fiber membrane with a solution and then pulverizing it using a homogenizing device consisting of a fixed outer blade with shearing force and a rotatable inner blade with a saw-like shape to obtain a dispersion.

[0059] In at least one specific embodiment of this disclosure, after the aforementioned homogenization and pulverization treatment, other additives may be added to the dispersion to aid in the dispersion of the intertwined bacterial cellulose. The additives may include, but are not limited to, other additives conventionally used in the art.

[0060] As used in this disclosure, the "swelling treatment" involves allowing the treatment solution to penetrate into the interwoven bacterial cellulose within the dispersion, thereby weakening the hydrogen bonds between cellulose molecules without causing excessive hydrolysis of the bacterial cellulose, thus reducing energy consumption in subsequent mechanical milling processes. In some specific embodiments of this disclosure, the synergistic effect of the shear force generated by combined mechanical milling can break the glycosidic bonds of bacterial cellulose, thereby causing bacterial cellulose fibrillation, increasing the specific surface area of ​​cellulose, and exposing more hydroxyl groups, thereby improving the hydrophilicity and biocompatibility of bacterial cellulose.

[0061] In at least one specific embodiment, the treatment solution disclosed herein may be selected from at least one of the group consisting of alkaline solutions, inorganic salt solutions, and aqueous solutions of ionic liquids. In some specific embodiments of this disclosure, the base forming the alkaline solution may include at least one selected from the group consisting of potassium hydroxide, sodium hydroxide, and lithium hydroxide; in some specific embodiments of this disclosure, the inorganic salt may be selected from at least one selected from the group consisting of urea, zinc chloride, urea sulfide, calcium chloride, and magnesium chloride; in some specific embodiments of this disclosure, the ionic liquid may be selected from at least one selected from the group consisting of 1-allyl-3-methylimidazolium chloride ([AMIm]Cl), 1-butyl-3-methylimidazolium chloride ([BMIm]Cl), 1-allyl-3-methylimidazolium acetate ([AMIm]Ac), 1-butyl-3-methylimidazolium acetate ([BMIm]Ac), lithium chloride / dimethyl sulfoxide (LiCl / DMSO), N-alkylpyridines, and dialkylimidazolides.

[0062] As used in this disclosure, "mechanical milling" includes milling the dispersion after dilution with water using a horizontal ball mill, causing the interwoven bacterial cellulose in the dispersion to separate into fibers, and largely determining the size of the bacterial cellulose in this process, for example, a diameter of 15 nm to 35 nm and a length of 100 nm to 3000 nm as described in this disclosure. The content of bacterial cellulose used for mechanical milling ranges from about 0.1 wt% to about 5 wt% of the total weight of the dispersion, such as about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1.0 wt%, about 1.2 wt%, about 1.5 wt%, about 1.8 wt%, 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, or about 5 wt%.

[0063] In addition to the above, the processing may also include purification. Purification may be performed last, for example, after homogenization, swelling and / or mechanical grinding, followed by purification of the dispersion, but is not limited thereto. Purification may refer to known methods, such as neutralization and / or desalting, for example, using a semipermeable membrane to separate salts from the dispersion to obtain the desired type of bacterial cellulose fibers.

[0064] In at least one embodiment of this disclosure, the milled bacterial cellulose has a high specific surface area, making the electrostatic effects, van der Waals forces, or hydrogen bonding between cellulose molecules more pronounced, which may lead to easy aggregation. Therefore, in some embodiments, this disclosure may further include treating the milled dispersion with ultrasonic vibration after mechanical milling to depolymerize the bacterial cellulose aggregates, and then freeze-drying may be performed as needed.

[0065] In some specific embodiments, the compositions disclosed herein may further include at least one of the group consisting of flavoring agents, dispersants, wetting agents, lubricants, thickeners, stabilizers, preservatives, antioxidants, antibacterial agents and colorants, and the bacterial cellulose of the present disclosure will not have a negative effect on the above-mentioned components.

[0066] In some specific embodiments of this disclosure, bacterial cellulose formed from β-1-4-glucan, or a composition containing said bacterial cellulose, can be administered when symptoms are anticipated to occur, before symptoms occur, or at the time of or after symptoms occur, to achieve preventative, therapeutic, and alleviating effects. For example, the composition of this disclosure is administered at a dose of 0.1 mg to 0.5 mg of said bacterial cellulose per kilogram of body weight, such as 0.1 mg, 0.15 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.35 mg, 0.4 mg, 0.45 mg, or 0.5 mg.

[0067] In some specific embodiments of this disclosure, bacterial cellulose formed from β-1-4-glucan or a composition containing said bacterial cellulose may be administered at or after the onset of symptoms to relieve symptoms. In some specific embodiments of this disclosure, the administration method may be as described above.

[0068] In at least one embodiment of this disclosure, bacterial cellulose formed from β-1-4-glucan or a composition containing said bacterial cellulose may be administered nasally twice daily at intervals of 1 to 12 hours, for example, at intervals of 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, or 12 hours, to treat or relieve symptoms of airway disease. In some embodiments of this disclosure, bacterial cellulose formed from β-1-4-glucan or a composition containing said bacterial cellulose may be administered before meals, after meals, at bedtime, or at the onset of symptoms. In one embodiment, bacterial cellulose formed from β-1-4-glucan or a composition containing said bacterial cellulose may be administered nasally three times daily at intervals of 4 to 8 hours. Depending on the circumstances, more than three doses may be administered, such as four doses, to obtain more pronounced symptom relief.

[0069] The present disclosure will be further described in detail below through specific embodiments, but the scope of the present disclosure shall not be limited by the embodiments.

[0070] Test Example 1: Animal Experiment

[0071] 1.1 Establishment of animal toxicity experimental models

[0072] Twelve SPF-grade female C57BL / 6 mice were housed in the SPF-grade animal room on the 3rd floor of the Animal Experiment Center at Nanfang Hospital. The mice were randomly divided into three groups (control group; 2 mg / kg BC group; 4 mg / kg BC group), with four mice per group. Starting from day 0, after isoflurane anesthesia, the control group received 20 μL of PBS via intranasal instillation daily, while the 2 mg / kg BC group and the 4 mg / kg BC group received 20 μL of the corresponding concentration of BC composition via intranasal instillation daily. (The BC composition was obtained by dispersing bacterial cellulose with a diameter of 15 nm to 35 nm and a length of 150 nm to 1000 nm, obtained by processing and grinding cellulose produced by *Acetobacter xylinum* according to the aforementioned method, in PBS, to achieve doses of 2 mg and 4 mg of bacterial cellulose per kilogram of body weight, respectively. Administration continued for 14 days, and samples were collected within 24 hours after administration on day 14.

[0073] 1.2 Preparation of animal models of asthma

[0074] Twenty SPF-grade female C57BL / 6 mice were housed in the SPF-grade animal room on the 3rd floor of the Animal Experiment Center at Nanfang Hospital. The mice were randomly divided into four groups (control group; HDM group; HDM + 2 mg / kg BC group; HDM + 4 mg / kg BC group), with five mice per group. The animal experimental protocol can refer to previous studies, such as Huang H, Qiao Y, Chu L, et al. Up-regulation of HSP90α in HDM-induced asthma causes pyroptosis of airway epithelial cells by activating the cGAS-STING-ER stress pathway. Int Immunopharmacol.

[0075] 1.2.1 Sensitization of animals in HDM asthma model

[0076] 100 μL of 4000 U HDM (Antoda's house dust mite allergen preparation 100000 SQ-U / ml) was prepared by mixing 60 μL PBS with 40 μL HDM. Mice in the HDM group, HDM+2 mg / kg BC group, and HDM+4 mg / kg BC group were intraperitoneally injected with 100 μL of 4000 U HDM on day 0 and day 7 of model animal establishment.

[0077] 1.2.2 Provocation and Treatment in Animal Models of Hyperdiabetes Mellitus (HDM)

[0078] 10 μL of 400U HDM (Antoda's house dust mite allergen preparation 100,000 SQ-U / ml) was prepared using 6 μL PBS and 4 μL HDM. Mice in the HDM group, HDM+2 mg / kg BC group, and HDM+4 mg / kg BC group were administered this solution daily from day 8 to day 21 after isoflurane inhalation anesthesia. One hour after HDM administration, mice in the HDM+2 mg / kg BC group and HDM+4 mg / kg BC group were given 20 μL of the corresponding concentration of the BC composition (the BC composition was obtained by dispersing bacterial cellulose with a diameter of 15 nm to 35 nm and a length of 150 nm to 1000 nm, produced by Acetobacter xylinum, in PBS after processing and grinding according to the aforementioned method), to achieve a dose of 2 mg and 4 mg of bacterial cellulose per kilogram of body weight, respectively. Samples were collected within 24 hours after administration on day 21.

[0079] 1.3 ELISA assay method for bronchoalveolar lavage fluid

[0080] The left lung of each group of mice collected in test example 1.2.2 was ligated, and the right lung tissue of the mice was irrigated with 1.5 ml of physiological saline three times. The bronchoalveolar lavage fluid of the mice was collected, and the expression levels of IL-4, IL-5, IL-13, IL-25, IL-33 and TSLP in the bronchoalveolar lavage fluid of the mice were tested using the corresponding index ELISA detection kit (crystal antibody). After the reaction was terminated, the brightness was detected using an enzyme-linked immunosorbent assay (ELISA) reader.

[0081] 1.4 HE staining of mouse lung tissue

[0082] Left lung tissues from mice in each group of test cases 1.1 and 1.2.2 were collected, fixed with paraformaldehyde, embedded in paraffin, serially sectioned, and dewaxed and rehydrated. The tissues were then stained with biosharp, mounted, and observed and photographed under a microscope.

[0083] 1.5 PAS staining of mouse lung tissue

[0084] Left lung tissues from mice in each group of test cases 1.1 and 1.2.2 were collected, fixed with paraformaldehyde, embedded in paraffin, serially sectioned, and dewaxed and rehydrated. The tissues were then stained with glycogen PAS staining kit (Solarbio), mounted, and observed and photographed under a microscope.

[0085] 1.6 Immunofluorescence staining of mouse lung tissue

[0086] Left lung tissue from mice in each group of test cases 1.2.2 was collected, fixed with paraformaldehyde, embedded in paraffin, serially sectioned, and dewaxed and rehydrated. Antigen retrieval and blocking were performed on the tissue sections. The sections were then incubated overnight at 4°C with primary antibodies against airway epithelial barrier-related proteins β-catenin, E-cadherin, and ZO-1 (protein tech). Secondary antibody (Alexa Fluor Plus 594) was added and incubated at room temperature for 1 hour. The sections were then stained with DAPI (Beyotime) for 5 minutes, mounted with anti-fluorescence quenching agent, and observed and photographed under a fluorescence microscope.

[0087] 1.7 Experimental Results

[0088] Numerous studies have been conducted on the use of BC in disease treatment, and its good biocompatibility and safety have been verified. However, there is a lack of sufficient research on the use of BC in the lungs. Due to the special anatomical structure and immune environment of the lungs, in order to determine whether BC can be used safely in the lungs, referring to the maximum oral gavage dose in the previous study of acute oral toxicity experiment of BC, the inventors set two administration doses as described in Test Example 1.1 above, namely 2 mg / kg and 4 mg / kg, to investigate whether the use of BC in the lungs will cause damage.

[0089] like FIG. 1A The dosing regimen shown involved administering different concentrations of BC via intranasal instillation to mice for 14 consecutive days, with samples collected within 24 hours of the last administration. Changes in mouse body weight were recorded over the 14-day period. FIG. 1B (n=4), showing no statistically significant difference in weight change over 14 days among the groups. In the lung tissue pathological sections obtained according to test cases 1.4 and 1.5 ( FIG. 1C (n=4, magnification 200x) HE staining showed no obvious destruction, proliferation, or inflammatory cell infiltration in the lung interstitium, and no obvious airway damage. Furthermore, PAS glycogen staining showed no goblet cell proliferation or increased mucus secretion. These experimental results indicate that intrapulmonary administration of BC at doses of 2 mg / kg and 4 mg / kg via nasal drops does not cause death, cachexia, or acute lung injury in mice, demonstrating the feasibility of intrapulmonary administration of BC via nasal drops.

[0090] After confirming the safety and feasibility of intrapulmonary administration of two doses of BC, as shown in Test Case 1.2 and... FIG. 2AThe illustrated scheme constructed an HDM-induced mouse asthma model, and the obtained mouse lung tissue was tested using the methods described in Test Examples 1.4 and 1.5 above. Among these tests, HE-stained sections ( FIG. 2B The results showed that, compared to the model group (i.e., the HDM group), airway damage was reduced in both different doses of BC treatment groups (i.e., HDM + 2 mg / kg BC group and HDM + 4 mg / kg BC group), and the continuity of airway epithelium and the shedding of airway epithelial cells were significantly improved in the treatment groups compared to the model group. PAS-stained sections ( FIG. 2B Compared to the model group, mice in the BC treatment group showed reduced airway mucus secretion and goblet cell proliferation. In other words, histopathological staining of tissue sections indicated that intrapulmonary administration of BC via nasal drops in a mouse model of HDM-induced asthma could indeed alleviate airway epithelial damage and reduce mucus secretion.

[0091] The bronchoalveolar lavage fluid (BALF) ELISA assay described in Test Example 1.3 above showed that in two different doses of BC treatment groups (i.e., HDM + 2 mg / kg BC group and HDM + 4 mg / kg BC group), the inflammatory marker IL-13 of type II asthma ( FIG. 2C ),IL-5( FIG. 2D The expression levels of IL-5 in all groups decreased significantly compared to the HDM group, with statistically significant differences observed. In particular, the IL-5 expression level in the HDM + 2 mg / kg BC group even recovered to the control group level. Furthermore, surprisingly, the epithelial cell-associated alarmins IL-25, IL-33, and TSLP all recovered to the control group levels in all different doses of BC treatment groups. FIGS. 2E to 2G In other words, BALF inflammatory factor ELISA assay showed that intrapulmonary administration of BC via nasal drops in a mouse model of HDM-induced asthma could reduce airway inflammation in asthma.

[0092] To further verify whether airway epithelial barrier function impairment was improved after BC treatment, the inventors used immunofluorescence assays described in Test Example 1.6 to detect the expression of tight junction proteins and adhesion connexins (E-cadherin, ZO-1, β-catenin) in airway epithelial cells from mouse lung tissue sections. In the HDM + 4 mg / kg BC group, the expression of tight junction proteins and adhesion connexins in airway epithelial cells returned to normal levels. FIG. 2H and 2I Furthermore, the levels of each protein in the HDM+2mg / kg BC group were also improved compared to the HDM group. This further confirms that intrapulmonary administration of BC via nasal drops can effectively reduce airway epithelial damage and inflammatory factor secretion in an HDM-induced asthma model.

[0093] This test case has demonstrated that, in a mouse model, BC at doses of 2 mg / kg and 4 mg / kg exhibits good safety and the desired therapeutic effect in reducing airway damage caused by asthma. Based on general conversion methods in the art, the mouse dose is approximately 9.01 times that of a human (based on a 60 kg body weight). Therefore, it can be anticipated that when administering the bacterial cellulose of this invention to a 60 kg adult, the suitable dose is approximately 0.1 mg to 0.5 mg per kg body weight.

[0094] Test Example 2: Cell Experiment

[0095] 2.1 Construction and Treatment of Cellular Asthma Model

[0096] BEAS-2B cells were cultured in DMEM / 10% FBS medium and stimulated with 800U HDM (Antoda's house dust mite allergen preparation 100,000 SQ-U / ml) for 48 hours to induce asthma. The control group was not stimulated with HDM; the HDM group was stimulated with 800U HDM for 48 hours; the HDM+0.4g / ml BC group, HDM+0.8g / ml BC group, HDM+1.6g / ml BC group, and HDM+3.2g / ml BC group were treated with 800U HDM with 0.8g BC, 800U HDM with 1.6g BC, 800U HDM with 3.2g BC, and 800U HDM with 6.4g BC, respectively, for 48 hours. The BC is bacterial cellulose with a diameter of 15 to 35 nanometers and a length of 150 to 1000 nanometers, obtained by processing and grinding cellulose produced by Acetobacter xylinum according to the aforementioned method.

[0097] 2.2 CCK8 Cytotoxicity Assay

[0098] BEAS-2B cells were seeded into 96-well plates at a density of 1 × 10⁶ cells per well. 4The cells were cultured until the cell density reached 60%. Then, the DMEM / 10% FBS medium was replaced with DMEM medium, and different concentrations of BC (0 mg / L, 3.28 mg / L, 6.56 mg / L, 13.12 mg / L, and 26.24 mg / L BC in PBS, wherein the BC is bacterial cellulose with a diameter of 15 nm to 35 nm and a length of 150 nm to 1000 nm, obtained by treating and grinding cellulose produced by *Acetobacter xylinum* according to the aforementioned method) were added for stimulation for 48 hours. After culturing at 37°C and 5% CO2 for 48 hours, the medium in each well was replaced with a 1:10 volume mixture of CCK-8 reagent and DMEM medium. Next, the cells were incubated in a light-protected cell incubator for 1 hour and 30 minutes. The absorbance of each well at 450 nm was measured using a multi-functional microplate reader, and cell viability was calculated using the following formula: Cell viability = [OD value of test wells - OD value of background wells] / [OD value of control wells - OD value of background wells] × 100%.

[0099] 2.3 Western Blotting

[0100] Protease inhibitors and protease phosphate inhibitors were added to high-intensity RIPA at a ratio of 1:100 to extract whole-cell proteins from each group of cells in Test Example 2.1. Proteins were separated by 8% and 12% SDS-PAGE gels and transferred to PVDF membranes. PVDF membranes were blocked with membrane rapid blocking buffer at room temperature for 8 minutes, incubated overnight at 4°C with primary antibodies against β-catenin and E-cadherin (Protein Tech), labeled with near-infrared DyLight fluorescent secondary antibody, and developed using an Odyssey LI-COR infrared fluorescence spectrometer.

[0101] 2.4 Cellular Immunofluorescence

[0102] Cells in each group of test example 2.1 were fixed with 4% paraformaldehyde at room temperature for 10 minutes, permeabilized with 0.1% Triton-X100 for 10 minutes, blocked with 5% BSA at room temperature for 1 hour, and then incubated overnight at 4°C with primary antibodies (CST) of ZO-1 and E-cadherin. Then, secondary antibody (Alexa Fluor Plus 594) was added and incubated at room temperature for 1 hour. Cells were stained with DAPI (Beyotime) at a 1:1 dilution at room temperature for 2 minutes and observed and photographed using a confocal microscope.

[0103] 2.5 Experimental Results

[0104] The animal experiments in Test Example 1 above showed that the use of BC in an asthma animal model could alleviate asthma symptoms and improve airway epithelial damage. The inventors also observed that airway epithelial cells may be the main cells acting on BC. Therefore, the following experiments will verify whether BC improves asthma symptoms by acting on airway epithelial cells. First, an asthma model was constructed using human bronchial epithelial cell line (BEAS-2B) cells via HDM stimulation, and the specific experimental method is described in Test Example 2.1 above.

[0105] Next, in order to select a suitable stimulation concentration and verify cytotoxicity, the inventors first used the CCK8 cytotoxicity assay described in Test Example 2.2 above to screen for a suitable concentration. For example... FIG. 3A As shown, at a concentration of 3.28 mg / L, BC does not cause airway epithelial cell death.

[0106] To further select a suitable therapeutic concentration, asthma cell models prepared in Test Example 2.1 were co-treated with BC at concentrations of 0.4 g / ml, 0.8 g / ml, 1.6 g / ml, and 3.2 g / ml and 800 U HDM. The protein imprinting method described in Test Example 2.3 was then used to verify the effect of different concentrations of BC at varying concentrations on the expression levels of representative proteins of tight junctions and adhesion junctions (β-catenin and E-cadherin). FIG. 3B As shown, 0.4 g / ml and 0.8 g / ml BC had good effects in improving epithelial cell damage caused by HDM stimulation.

[0107] To further verify the ability of different concentrations of BC to improve epithelial barrier damage, the expression of tight junction and adhesion junction proteins (ZO-1, E-cadherin) in different groups of cells was verified using the immunofluorescence assay described in Test Example 2.4 above. FIG. 3C The results showed that 0.8 g / ml BC had a better effect on improving the damage caused by HDM stimulation, suggesting that at appropriate therapeutic concentrations, higher concentrations lead to better therapeutic effects.

[0108] As demonstrated by the above test examples, the bacterial cellulose disclosed herein exhibits good safety and can improve epithelial cell damage, restore the epithelial continuity of airway epithelial cells, reduce cell shedding, reduce airway mucus secretion, reduce goblet cell proliferation, and reduce inflammatory response. This, in turn, improves epithelial barrier damage and achieves therapeutic or preventative effects on airway diseases, especially those related to epithelial cell damage (such as asthma), demonstrating promising application prospects.

[0109] The above embodiments are merely illustrative and not intended to limit this disclosure. Any person skilled in the art can modify and alter the above embodiments without departing from the spirit and scope of this disclosure. Therefore, the scope of protection of this disclosure is defined by the appended claims, and should be covered by the technical content of this disclosure as long as it does not affect the effect and purpose of implementation.

Claims

1. Use of a composition for the manufacture of a medicament for the treatment or prevention of airway disease, wherein, The composition comprises bacterial cellulose formed from beta-1-4-glucan, and the bacterial cellulose has a diameter of 15 nm to 35 nm and a length of 100 nm to 3000 nm.

2. Use according to claim 1, wherein, The aspect ratio of the bacterial cellulose is 2.5 to 86.

3. Use according to claim 1, wherein, The content of the bacterial cellulose in the composition is 0.2 wt% to 1.2 wt%.

4. The use according to claim 1, wherein, The composition is administered to the individual in need thereof in a dose of 1 to 4 times a day, and the dose of the composition administered each time is 0.1 mg to 0.5 mg of the bacterial cellulose per kg of body weight.

5. Use according to claim 4, wherein, The composition is administered to the individual nasally or by inhalation, the nasal administration includes in the form of drops or sprays, and the inhalation administration includes in the form of an atomizer or a dry powder.

6. The use according to claim 1, wherein, The composition further comprises a carrier in which the bacterial cellulose is dispersed, and the carrier is selected from the group consisting of water, physiological saline, a buffer, and Ringer's solution.

7. The use according to claim 1, wherein, The composition further comprises at least one selected from the group consisting of a flavoring agent, a dispersing agent, a wetting agent, a lubricant, a thickening agent, a stabilizer, a preservative, an antioxidant, an antibacterial agent, and a coloring agent.

8. The use according to claim 1, wherein, The bacterial cellulose is formed from at least one bacteria selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, and Agrobacterium.

9. The use according to claim 1, wherein, The airway disease is selected from the group consisting of asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, bronchitis, allergic rhinitis, chronic cough, and alveolitis.

10. Use according to claim 9, wherein, The airway disease is asthma.

Images