Use of bacterial cellulose for the treatment or prevention of respiratory tract diseases

Abstract

The application of nanomaterials to respiratory diseases is still very limited. Due to the unique anatomical structure and immune environment of the lungs, developing nanomaterials with smaller particle sizes, greater uniformity, superior in vivo stability, milder compositions, and superior biocompatibility is of great importance. [Solution] The present invention discloses the use of bacterial cellulose for the treatment or prevention of airway diseases, in particular for the treatment or prevention of inflammatory airway diseases such as asthma, which are associated with damage to airway epithelial cells.

Description

[Technical Field]

[0001] This invention relates to the use of bacterial cellulose for the treatment or prevention of airway diseases, and more particularly to the use of bacterial cellulose for the treatment or prevention of inflammatory airway diseases exacerbated by damage to airway epithelial cells. [Background technology]

[0002] Asthma is a chronic airway disease characterized by airway inflammation, airway hyperresponsiveness, and increased mucus secretion. Airway epithelial cells play a crucial role in the pathogenesis of asthma. When environmental allergens or pathogens come into contact with epithelial cells, they are known to secrete and release large amounts of inflammatory factors (IL-25, IL-33, TSLP, etc.). The release of these epithelial inflammatory factors (also called alarmins) can activate large amounts of immune cells, such as Th2 and ILC2 cells, ultimately leading to eosinophilic airway inflammation and sometimes directly activating mast cells, causing airway inflammation and airway hyperresponsiveness.

[0003] Epithelial cell destruction is seen in all phenotypes of asthma. The airway epithelial cells of asthma patients are destroyed, characterized by epithelial cell detachment and decreased expression of intercellular adhesion molecules such as tight junction proteins (e.g., ZO-1, claudins, occludin, TJP2) and adhesion proteins (β-catenin and E-cadherin). As a result, barrier function is impaired and permeability to external pathogens and allergens increases. On the other hand, epithelial cell damage and decreased expression of intercellular tight junction proteins and adhesion proteins increase the likelihood of epithelial-mesenchymal transition (EMT) occurring in airway epithelial cells, worsening airway remodeling in asthma patients and consequently exacerbating asthma.

[0004] The aforementioned mechanisms of disease onset, including the destruction of epithelial cells and damage to barrier function, are also widely observed in other respiratory tract diseases. However, current treatments for respiratory tract diseases do not restore damaged epithelial cells, and therefore cannot completely cure respiratory tract diseases. Moreover, re-exposure to environmental allergens or pathogens causes respiratory tract disease.

[0005] Over the past decade, the rapid development of nanotechnology has led to the creation of a variety of materials with great therapeutic potential. Many functional nanomaterials with anti-inflammatory and antioxidant properties have been developed, including metal oxide nanoparticles (NPs), carbon nanomaterials, and precious metal NPs, and have been reported to be applicable to the treatment of diseases including stroke, sepsis, inflammatory bowel disease, neurodegenerative diseases, diabetes, acute kidney injury, and acute liver injury.

[0006] Cellulose is also one of the nanomaterials attracting attention as the most abundant natural polymer material on Earth, and in recent years, bacterial cellulose (BC), a highly crystalline linear glucose biopolymer produced by bacterial fermentation, has attracted even more attention. BC possesses unique physical and chemical properties such as high modulus of elasticity, high specific surface area, low density, non-abrasiveness, ease of surface functionalization, high purity of chemical components, high crystallinity, high degree of polymerization (2000-8000), and excellent biocompatibility and biodegradability. Bacterial cellulose has already been applied to wound dressings, vascular tissue engineering, and bone tissue regeneration, and has been proven to have good biocompatibility. [Overview of the project] [Problems that the invention aims to solve]

[0007] However, the application of nanomaterials to respiratory diseases remains very limited. Due to the unique anatomical structure and immune environment of the lungs, developing nanomaterials with smaller particle sizes, greater uniformity, superior in vivo stability, milder compositions, and superior biocompatibility is of great importance. [Means for solving the problem]

[0008] In view of the various shortcomings of the existing technologies described above, the present invention provides for the use of a composition for manufacturing a pharmaceutical for treating or preventing respiratory tract diseases, the composition comprising bacterial cellulose formed from β-1-4-glucan, the bacterial cellulose having a diameter of 15 nanometers to 35 nanometers and a length of 100 nanometers to 3000 nanometers.

[0009] In one specific embodiment, the length-to-diameter ratio of the bacterial cellulose is 2.5 to 86.

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

[0011] In one specific embodiment, the composition is administered to an individual in need in doses of 1 to 4 times per day, with a single dose of the composition being 0.1 to 0.5 milligrams of bacterial cellulose per kilogram of body weight.

[0012] In one specific embodiment, the composition is administered to the individual via nasal or inhalation, preferably with nasal administration in the form of drops or sprays, and inhalation administration in the form of a nebulizer or dry powder.

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

[0014] In one specific embodiment, the composition further comprises at least one from the group consisting of seasonings, dispersants, wetting agents, lubricants, thickeners, stabilizers, preservatives, antioxidants, antimicrobial agents, and colorants.

[0015] 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, and preferably, the bacterial cellulose is formed by bacteria of the Gluconacetobacter and / or Acetobacter genera.

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

[0017] Furthermore, the present invention provides a method for treating or preventing respiratory diseases, the method comprising administering a therapeutically effective amount of a composition comprising bacterial cellulose formed from β-1-4-glucan to an individual in need thereof, wherein the bacterial cellulose has a diameter of 15 nanometers to 35 nanometers and a length of 100 nanometers to 3000 nanometers.

[0018] In one specific embodiment, the length-to-diameter ratio of the bacterial cellulose is 2.5 to 86.

[0019] In one specific embodiment, the bacterial cellulose content in the composition is 0.2% to 1.2% by weight.

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

[0021] In one specific embodiment, the composition is administered to the individual by nasal administration or inhalation administration. Preferably, the nasal administration includes forms by nasal drops or nasal sprays, and the inhalation administration includes forms by nebulizers or dry powders.

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

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

[0024] 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 the genus Acetobacter.

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

[0026] The present invention also provides the use of a composition containing bacterial cellulose formed from β-1,4-glucan for the treatment or prevention of airway diseases, and the bacterial cellulose has a diameter of 15 nanometers to 35 nanometers and a length of 100 nanometers to 3000 nanometers.

[0027] In one specific embodiment, the length-to-diameter ratio of the bacterial cellulose is 2.5 to 86.

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

[0029] In one specific embodiment, the composition is administered to an individual who needs it at a dose of 1 to 4 times a day, and the dose of the composition administered each time is 0.1 milligram to 0.5 milligram of the bacterial cellulose per kilogram of body weight.

[0030] In one specific embodiment, the composition is administered to the individual by nasal administration or inhalation administration, and preferably, the nasal administration includes forms by nasal drops or nasal sprays, and the inhalation administration includes forms by nebulizers or dry powders.

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

[0032] In one specific embodiment, the composition further includes at least one selected from the group consisting of flavoring agents, dispersing agents, wetting agents, lubricants, thickening agents, 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, and preferably, the bacterial cellulose is formed by bacteria of the Gluconacetobacter and / or Acetobacter genera.

[0034] In one specific embodiment, the airway disease is selected from asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, bronchitis, allergic rhinitis, chronic cough, and alveolitis, and preferably, the airway disease is asthma. [Effects of the Invention]

[0035] Specifically, the bacterial cellulose used in this invention has good biocompatibility in the lungs and maintains homeostasis of the airway epithelial barrier. This makes the use of bacterial cellulose in the lungs feasible and demonstrates that it can effectively restore damaged epithelial barrier function and reduce inflammatory symptoms in airway diseases such as asthma, thus filling a gap in current treatments for airway diseases. [Brief explanation of the drawing]

[0036] [Figure 1A] Figure 1 shows the results of animal toxicity experiments conducted on bacterial cellulose according to the present invention. Figure 1A shows the administration scheme for the toxicity experiment. [Figure 1B] This figure shows that there were no statistically significant differences in body weight changes between the mice in each group during the toxicity experiment. [Figure 1C]These are images of lung histopathological section staining (H&E and PAS) from mice in each group. [Figure 2A] Figure 2 shows the experimental results of reducing airway injury and inflammatory responses in an animal asthma model using bacterial cellulose according to the present invention. Figure 2A shows the administration scheme in a mouse asthma model induced by HDM. [Figure 2B] These are images of lung histopathological section staining (H&E and PAS) from mice in each group. [Figure 2C] This figure shows the expression levels of the inflammatory factor IL-13 in bronchoalveolar lavage fluid (BALF) from each group of mice. [Figure 2D] This figure shows the expression levels of the inflammatory factor IL-5 in bronchoalveolar lavage fluid (BALF) from each group of mice. [Figure 2E] This figure shows the expression levels of the inflammatory factor IL-25 in bronchoalveolar lavage fluid (BALF) from each group of mice. [Figure 2F] This figure shows the expression levels of the inflammatory factor IL-33 in bronchoalveolar lavage fluid (BALF) from each group of mice. [Figure 2G] This figure shows the expression levels of the inflammatory factor TSLP in the bronchoalveolar lavage fluid (BALF) of mice from each group. [Figure 2H] These are immunofluorescence staining images of tight junction protein (ZO-1) and adhesion proteins (β-catenin and E-cadherin) in lung tissue epithelial cells of mice from each group, with a scale of 50 μm. [Figure 2I] Figure 2H shows histograms obtained after quantifying the immunofluorescence staining. From left to right, the data for each group containing ZO-1, β-catenin, and E-cadherin are shown, representing the control group, HDM group, HDM+2mg / kg BC group, and HDM+4mg / kg BC group. Numerical values ​​are shown 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. [Figure 3A]Figure 3 shows the experimental results of reducing airway damage in a cellular asthma model using bacterial cellulose according to the present invention. Figure 3A shows the experimental results of a CCK8 cytotoxicity test. [Figure 3B] The expression levels of β-catenin and E-cadherin of different concentrations of bacterial cellulose, as tested by Western blotting, are shown in the figure below. The results obtained after quantification are shown for each group of E-cadherin and β-catenin, from left to right, representing the 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, respectively. [Figure 3C] These are immunofluorescence staining images of tight junction protein (ZO-1) and adhesion protein (E-cadherin) in cells of each group. Analysis was performed using one-way ANOVA and Tukey's multirange test. * indicates P<0.05, ** indicates P<0.01, *** indicates P<0.001, and ns indicates no significant difference. [Figure 4] Figure 4 is an electron microscope image of the bacterial cellulose of the present invention. The image shows that the bacterial cellulose of the present invention is uniform in size, has good dispersibility, and does not tangle or aggregate. [Figure 5] Figure 5 is an electron microscope image of the bacterial cellulose of the present invention. The figure shows that the bacterial cellulose of the present invention has dimensions of 15 nanometers to 35 nanometers in diameter and 100 nanometers to 3000 nanometers in length. [Modes for carrying out the invention]

[0037] The embodiments of this disclosure will be described below by specific examples, but those skilled in the art will readily understand the advantages and effects of this disclosure from the content described herein. This disclosure can also be implemented or applied by other different embodiments, and the details of each item herein can be modified and altered in different ways based on different perspectives and applications, without departing from the spirit described herein.

[0038] In this disclosure, any statement that includes, contains, or has a particular requirement may, unless otherwise stated, further include, and does not exclude, other requirements such as other elements, components, structures, areas, parts, devices, systems, processes, or connections.

[0039] In this disclosure, unless otherwise explicitly stated, the singular “one” and “the said” as used herein include the plural, and “or” as used herein may be used interchangeably with “and / or.”

[0040] The numerical ranges described herein are inclusive and combinable, and all numerical values ​​within a numerical range described herein can be the maximum or minimum value for deriving its subranges. For example, the numerical range "diameter of 15 to 35 nanometers" should be understood to include all subranges between the minimum value of 15 nanometers and the maximum value of 35 nanometers, such as 15 to 30 nanometers, 16 to 35 nanometers, and 22 to 28 nanometers. Furthermore, if a numerical value falls within any of the ranges described herein (e.g., between the maximum and minimum values), it should be considered to be included within the scope of this disclosure.

[0041] The bacterial cellulose of this disclosure refers to cellulose produced by bacteria, for example, by bacterial fermentation culture, and is composed of D-glucose molecules linked together by β(1→4) glycosidic bonds, belonging to the β-1-4-glucan group. Unlike plant cellulose, bacterial cellulose has a higher purity.

[0042] In one specific embodiment, the bacterial cellulose has a diameter of 15 nanometers to 35 nanometers, for example, 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, the 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. Approximately 1500 nanometers, approximately 1550 nanometers, approximately 1600 nanometers, approximately 1650 nanometers, approximately 1700 nanometers, approximately 1750 nanometers, approximately 1800 nanometers, approximately 1850 nanometers, approximately 1900 nanometers, approximately 1950 nanometers, approximately 2000 nanometers, approximately 2050 nanometers, approximately 2100 nanometers, approximately 2150 nanometers, approximately 2200 nanometers, approximately 2250 nanometers The diameters are approximately 2300 nanometers, 2350 nanometers, 2400 nanometers, 2450 nanometers, 2500 nanometers, 2550 nanometers, 2600 nanometers, 2650 nanometers, 2700 nanometers, 2750 nanometers, 2800 nanometers, 2850 nanometers, 2900 nanometers, 2950 nanometers, or 3000 nanometers. In some specific embodiments of this disclosure, diameter refers to the average diameter and length refers to the 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 the present disclosure, the diameter of the bacterial cellulose is preferably 15 nanometers to 25 nanometers, and the length is preferably between 100 nanometers and 1000 nanometers, and preferably between 200 nanometers and 650 nanometers. In one specific embodiment, the length-to-diameter ratio of the bacterial cellulose is between 2.5 and 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.

[0043] In this disclosure, bacterial cellulose formed from β-1-4-glucan has a use in producing compositions for treating or preventing airway diseases, the use of which includes administering bacterial cellulose formed from β-1-4-glucan to an individual in need. In some specific embodiments of this disclosure, the compositions of this disclosure may be, but are not limited to, pharmaceutical compositions. In some specific embodiments of this disclosure, the airway disease may be asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, bronchitis, allergic rhinitis, chronic cough, or alveolitis, and 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.

[0044] In one specific embodiment, an individual requiring treatment or prevention of a respiratory tract disease may be directly administered nasally by bacterial cellulose or a composition thereof formed from β-1-4-glucan, for example, in the form of drops or sprays. In another specific embodiment, an individual requiring treatment or prevention of a respiratory tract disease may directly inhale bacterial cellulose or a composition thereof formed from β-1-4-glucan, for example, by oral or nasal inhalation, or by inhalation in the form of a nebulizer or dry powder.

[0045] In one specific embodiment, the bacterial cellulose formed from β-1-4-glucan of the present disclosure or a composition containing the same may be dried before use, for example, by freeze-drying to form freeze-dried tablets or powder in the form of dried blocks, or by further processing the dried powder into tablets. In some specific embodiments of the present disclosure, the bacterial cellulose or a composition containing the same may be subjected to at least one of the following steps: low-temperature freezing, low-temperature low-pressure extraction, and desorption, thereby improving the overall stability of the product, making it less susceptible to deterioration, and facilitating storage. When used, the bacterial cellulose fibers have excellent rehydration properties, and the dried product (such as freeze-dried tablets, powder, or tablets) is easily mixed with a liquid carrier, so a composition containing a liquid carrier and bacterial cellulose may be formed. In some specific embodiments of the present disclosure, the bacterial cellulose or a composition containing the same may be treated in the order of low-temperature freezing, low-temperature low-pressure extraction, and desorption, but it should be understood that the order of the treatment steps is not limited to these and can be appropriately adjusted according to the desired properties of the bacterial cellulose.

[0046] In some specific embodiments of the Disclosure, the compositions of the Disclosure can be used to prepare dosage forms commonly used for respiratory tract diseases, which are convenient for use by an individual or by another person on an individual. In some specific embodiments of the Disclosure, the dosage forms are, for example, drops or sprays for intranasal administration, or nebulizers or dry powders for inhalation administration. Of these, in addition to dry dosage forms such as dry powder, dosage forms such as drops, sprays, and nebulizers may contain a liquid carrier, which may contain, but is not limited to, non-irritating liquids such as water, saline, buffers, and Ringer's solution. When the compositions are provided to an individual in the form of drops, sprays, or nebulizers, since the compositions contain a liquid carrier, it is not necessary to pre-mix the bacterial cellulose produced in the Disclosure with the liquid carrier before using the compositions of the Disclosure.

[0047] In some specific embodiments of this disclosure, the bacterial cellulose content may be between 0.2% by weight and 1.2% by weight, based on the total weight of the composition, in order to increase its dispersion rate. For example, the fiber content may be about 0.2% by weight, about 0.3% by weight, about 0.4% by weight, about 0.5% by weight, about 0.6% by weight, about 0.7% by weight, about 0.8% by weight, about 0.9% by weight, about 1.0% by weight, about 1.1% by weight, or about 1.2% by weight. In some specific embodiments of this disclosure, if the fiber content is less than 0.2% by weight, the fibers may not be able to provide enough hydroxyl groups and may therefore affect the interfacial tension of the liquid medium to some extent. In some specific embodiments of this disclosure, if the fiber content is less than 0.2% by weight, the liquid medium and fibers may aggregate due to cohesive forces, which may result in layering and be detrimental to mixing.

[0048] In some specific embodiments, the bacteria used for bacterial cellulose production may be at least one species 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 of this disclosure, the bacteria of this disclosure may be at least one bacterium selected from the group consisting of Acetobacter xylinum (also known as Gluconacetobacter xylinus), Gluconacetobacter hansenii, and Gluconacetobacter sacchari. In some specific embodiments of this disclosure, strains of the genus Gluconacetobacter, 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 a number of strains may be selected for the production of bacterial cellulose, and this can be adjusted without limitation according to the actual needs.

[0049] To provide the preparation of bacterial cellulose of the present disclosure, a container containing a culture solution is prepared in advance, and the single strain or multiple strains are statically cultured in the container containing the culture solution for 24 to 96 hours (for example, 24, 36, 48, 60, 72, 84 or 96 hours). The absorbance of the bacterial concentration in the culture solution (the wavelength is 620 nm) is controlled within the range of 0.005 to 0.01, for example, about 0.005, about 0.006, about 0.007, about 0.008, about 0.009 or about 0.01. In some specific embodiments of the present disclosure, the pH value of the culture solution is controlled to an acidic environment including a pH value between 0.5 and 6.5, for example, about 0.5, about 1.0, about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0 or about 6.5. In some specific embodiments of the present disclosure, the concentration range of bacteria in the culture solution is 2 ~10 5 / milliliter, for example, about 1×10 2 / milliliter, about 5×10 2 / milliliter, about 1×10 3 / milliliter, about 5×10 3 / milliliter, about 1×10 4 / milliliter, about 5×10 4 / milliliter or about 1×10 5 / milliliter. In some specific embodiments of the present disclosure, the culture temperature may be controlled between 25°C and 30°C, for example, about 25°C, about 26°C, about 27°C, about 28°C, about 29°C or about 30°C. In some specific embodiments of the present disclosure, the absorbance of the bacterial concentration in the culture solution, the pH value of the culture solution, the concentration range of bacteria in the culture solution, the culture temperature or any combination thereof can be selected to control the culture of the bacteria of the present disclosure.

[0050] As used in this disclosure, "static culture" refers to the formation of a layered fibrous membrane in the form of a nonwoven fabric by bacteria on the surface of the culture medium (i.e., the gas-liquid interface). The container used for static culture can be a flat container with a large culture area, thereby controlling the oxygen consumption of the bacteria by reducing the height of the container, and further controlling the diameter of the bacterial cellulose. In some specific embodiments of this disclosure, the mesh structure formed by the fibers on the surface of the synthetic fibrous membrane has a higher density and is denser than the mesh structure inside the fibrous membrane, so that the subsequent separation of the interwoven bacterial cellulose can be facilitated by the static culture and culture conditions described above.

[0051] As used in this disclosure, the term “fibrous membrane” refers to a layered material formed by weaving together multiple fibers and having a multilayer network structure. In some specific embodiments of this disclosure, the thickness of the fibrous membrane may be between 20 micrometers and 30 micrometers, for example, about 20 micrometers, about 22 micrometers, about 24 micrometers, about 25 micrometers, about 26 micrometers, about 28 micrometers, or about 30 micrometers. In some specific embodiments of this disclosure, the amount of bacterial cellulose per unit area of ​​the fibrous membrane is between 0.001 grams / cm² and 0.002 grams / cm², for example, about 0.0011 grams / cm², about 0.0012 grams / cm², about 0.0013 grams / cm², about 0.0015 grams / cm², about 0.0017 grams / cm², about 0.0018 grams / cm², or about 0.0019 grams / cm². In some specific embodiments of the present disclosure, the diameter of the bacterial cellulose in the fibrous membrane is between 15 nanometers and 100 nanometers, for example, 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.

[0052] In at least one specific embodiment, the components of the culture medium may include a carbon source, a nitrogen source, and a gel support, of which the carbon source may include at least one type of 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, for example, agar. In some specific embodiments of the present disclosure, the culture medium may include agar, a carbon source, peptone, and yeast extract, where the weight ratio of the carbon source, peptone, and yeast extract may be 5:1:1 to 4:1:1.

[0053] In at least one specific embodiment of the present disclosure, the preparation of the fibrous membrane can be carried out by static fermentation of bacteria of the genus Gluconacetobacter in a culture medium containing mannitol, peptone, yeast extract and agar, wherein the prepared fibrous membrane has a water content of more than 85%, for example, more than 90%, more than 92%, or more than 95%.

[0054] In at least one specific embodiment, the bacterial cellulose of the present disclosure is obtained by obtaining a fibrous film by bacterial fermentation culture, and then further processing the fibrous film. To obtain the bacterial cellulose, the processing of the fibrous film includes a framing treatment of the fibrous film, the framing treatment includes at least one of the group consisting of homogeneous grinding, swelling treatment, and mechanical polishing. In at least one specific embodiment, the framing treatment includes, but is not limited to, homogeneous grinding, swelling treatment, and mechanical polishing performed in sequence.

[0055] As used in this disclosure, "homogenized grinding" refers to a process in which a fibrous membrane is mixed with a solution, and then ground using a homogenization device consisting of, for example, a fixed outer blade having shearing force and a rotatable inner blade having a sawtooth shape, in order to produce a dispersion.

[0056] In at least one specific embodiment of the present disclosure, other additives may be further added to the dispersion after the homogenization process to help disperse the interwoven bacterial celluloses. These additives may include, but are not limited to, other additives commonly used in the art.

[0057] The "swelling treatment" used in this disclosure involves infiltrating the treatment solution into the interwoven bacterial cellulose in the dispersion, thereby weakening the hydrogen bonding between celluloses and preventing excessive hydrolysis of the bacterial cellulose, thus reducing energy consumption during subsequent mechanical polishing. In some specific embodiments of this disclosure, the synergistic effect of shear force combined with mechanical polishing can cleave the glycosidic bonds of the bacterial cellulose and further fibrousize it, increasing the specific surface area of ​​the cellulose and exposing more hydroxyl groups, thereby improving the hydrophilicity and biocompatibility of the bacterial cellulose.

[0058] In at least one specific embodiment of the Disclosure, the treatment solution can 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 the 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 the Disclosure, the inorganic salt can be selected from at least one of the group consisting of urea, zinc chloride, urea sulfide, calcium chloride, and magnesium chloride. In some specific embodiments of this disclosure, the ionic liquid can be selected from at least one of 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 dialkylimidazoles.

[0059] The "mechanical polishing" as used in this disclosure includes diluting a dispersion with water, then polishing it in a horizontal ball mill to separate the interwoven bacterial cellulose in the dispersion, and in this process, the dimensions of the bacterial cellulose are roughly determined, for example, the dimensions of 15 nanometers to 35 nanometers in diameter and 100 nanometers to 3000 nanometers in length as exemplified in this disclosure. Here, the range of bacterial cellulose content used for mechanical polishing is between approximately 0.1% by weight and approximately 5% by weight relative to the total weight of the dispersion, for example, approximately 0.1% by weight, approximately 0.2% by weight, approximately 0.3% by weight, approximately 0.4% by weight, approximately 0.5% by weight, approximately 0.6% by weight, approximately 0.7% by weight, approximately 0.8% by weight, approximately 0.9% by weight, approximately 1.0% by weight, approximately 1.2% by weight, approximately 1.5% by weight, approximately 1.8% by weight, 2% by weight, approximately 2.5% by weight, approximately 3% by weight, approximately 3.5% by weight, approximately 4% by weight, approximately 4.5% by weight, or approximately 5% by weight.

[0060] In addition to the above, the processing may further include a purification process. The purification process may be performed last, and the dispersion may be further purified after, for example, homogenization, swelling, and / or mechanical polishing. The purification process may refer to known methods, for example, neutralization and / or desalting, and for example, bacterial cellulose fibers in the desired form may be obtained by dialysis separation of salts in the dispersion using a semipermeable membrane.

[0061] In at least one specific embodiment of the present disclosure, polished bacterial cellulose may have a high specific surface area, and the electrostatic effects, van der Waals forces, or hydrogen bonding forces between celluloses may become more pronounced, potentially leading to a tendency for aggregation. Therefore, in some specific embodiments, the present disclosure may further include, after mechanical polishing, treating the polished dispersion by ultrasonic vibration to depolymerize the aggregates of bacterial cellulose, and then, depending on the actual needs, lyophilization may be selected.

[0062] In some specific embodiments, the compositions of the Disclosure may further include at least one of the group consisting of flavorings, dispersants, wetting agents, lubricants, thickeners, stabilizers, preservatives, antioxidants, antimicrobial agents, and colorants, without adverse effects between the bacterial cellulose of the Disclosure and each of the above components.

[0063] In some specific embodiments of the present disclosure, preventive, therapeutic, and remission effects can be achieved by administering bacterial cellulose formed from β-1-4-glucan or a composition containing said bacterial cellulose when the onset of symptoms is foreseeable, before the onset of symptoms, during the onset of symptoms, or after the onset of symptoms. For example, the dose of the composition of the present disclosure is 0.1 to 0.5 milligrams of said bacterial cellulose per kilogram of body weight, for example, 0.1 milligrams, 0.15 milligrams, 0.2 milligrams, 0.25 milligrams, 0.3 milligrams, 0.35 milligrams, 0.4 milligrams, 0.45 milligrams, or 0.5 milligrams.

[0064] In some specific embodiments of the present disclosure, symptoms can be relieved by administering bacterial cellulose formed from β-1-4-glucan or a composition containing said bacterial cellulose at the time of or after the onset of symptoms. In some specific embodiments of the present disclosure, the method of administration may be as described above.

[0065] In at least one specific embodiment of this disclosure, bacterial cellulose formed from β-1-4-glucan or a composition containing said bacterial cellulose may be administered intranasally twice daily at intervals of 1 to 12 hours, for example, 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 alleviate symptoms of airway disease. 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 before meals, after meals, before bedtime, or during symptom attacks. In one specific embodiment, bacterial cellulose formed from β-1-4-glucan or a composition containing said bacterial cellulose may be administered intranasally three times daily at intervals of 4 to 8 hours. Depending on the situation, more than three doses (e.g., four doses) may be administered to achieve more pronounced symptom relief. [Examples]

[0066] The present disclosure will be described in more detail below with reference to specific examples, but the scope of the present disclosure is not limited by the description of the examples.

[0067] Test Example 1: Animal Experiment 1.1 Establishment of animal toxicity experimental models Twelve SPF-grade female C57BL / 6 mice were selected and housed in the SPF-grade animal room on the 3rd floor of the Animal Experiment Center at Southern Hospital. The mice were randomly divided into three groups (control group, 2 mg / kg BC group, and 4 mg / kg BC group), with 4 mice per group. Starting on day 0, after isoflurane anesthesia, the control group received 20 μL of PBS intranasally 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 intranasally daily, so that the bacterial cellulose doses were 2 mg and 4 mg per kilogram of body weight, respectively (the BC composition was obtained by dispersing bacterial cellulose with a diameter of 15 to 35 nanometers and a length of 150 to 1000 nanometers, obtained by processing and polishing cellulose produced from Acetobacter xylinum using the method described above, in PBS). The drug was administered continuously for 14 days, and samples were collected within 24 hours after the 14th day's administration.

[0068] 1.2 Preparation of an animal model of asthma Twenty SPF-grade female C57BL / 6 mice were selected and housed in the SPF-grade animal room on the 3rd floor of the Animal Experiment Center at Southern 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 5 mice per group. The animal study scheme can be referenced from previous studies, for example, 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.

[0069] 1.2.1 Sensitization of HDM asthma model animals Using 60 μL of PBS and 40 μL of HDM, 100 μL of 4000U HDM (Alutard SQ indoor dust mite allergen preparation 100,000 SQ-U / ml) was added. 100 μL of 4000U HDM was intraperitoneally injected into mice in the HDM group, HDM + 2 mg / kg BC group, and HDM + 4 mg / kg BC group on days 0 and 7 of the modeling period in the animal models.

[0070] 1.2.2 Induction and Treatment of HDM Asthma in Animal Models Using 6 μL of PBS and 4 μL of HDM, 10 μL of 400 U HDM (Alutard SQ indoor dust mite allergen preparation 100,000 SQ-U / ml) was mixed and administered daily to mice in the HDM group, HDM + 2 mg / kg BC group, and HDM + 4 mg / kg BC group after isoflurane inhalation anesthesia from day 8 to day 21 of the modeling period. Additionally, 1 hour after HDM administration, 20 μL of the BC composition at the corresponding concentration was administered to the HDM + 2 mg / kg BC group and HDM + 4 mg / kg BC group mice, so that the bacterial cellulose doses were 2 mg and 4 mg per kilogram of body weight, respectively (the BC composition was obtained by dispersing bacterial cellulose with a diameter of 15 to 35 nanometers and a length of 150 to 1000 nanometers, obtained by processing and polishing cellulose produced from Acetobacter xylinum in the method described above, in PBS). Samples were collected within 24 hours after administration on day 21.

[0071] 1.3 Method for ELISA analysis of bronchoalveolar lavage fluid In the above Test Example 1.2.2, the left lungs of each group of mice from which samples were collected were ligated, and the right lung tissue of the mice was washed in three separate stages using 1.5 ml of physiological saline to collect the alveolar lavage fluid of the mice. The expression levels of IL-4, IL-5, IL-13, IL-25, IL-33, and TSLP in the alveolar lavage fluid of the mice were tested using the corresponding ELISA detection kit (Crystal Anti). After the reaction was complete, the luminescence intensity was detected using an enzyme label analyzer.

[0072] 1.4 H&E staining of mouse lung tissue Left lung tissue was collected from each group of mice whose samples were collected in the above-mentioned test examples 1.1 and 1.2.2. After paraformaldehyde fixation, paraffin embedding, preparation of serial sections, and dewaxing and rehydration of the sections, the tissue was stained with hematoxylin-eosin (biosharp), the sections were mounted, and observed and photographed under a microscope.

[0073] 1.5 PAS staining of mouse lung tissue Left lung tissue was collected from each group of mice whose samples were recovered in the above-mentioned test examples 1.1 and 1.2.2. After paraformaldehyde fixation, paraffin embedding, preparation of serial sections, and dewaxing and rehydration of the sections, the tissue was stained using a glycogen PAS staining kit (Solarbio), the sections were mounted, and observed and photographed under a microscope.

[0074] 1.6 Immunofluorescence staining of mouse lung tissue Left lung tissue was collected from each group of mice whose samples were recovered in the above-mentioned Test Example 1.2.2. After paraformaldehyde fixation, paraffin embedding, serial section preparation, and dewaxing and rehydration of the sections, antigen reuptake and blocking were performed on the tissue sections. Primary antibodies (Proteintech) for the airway epithelial barrier-related proteins β-catenin, E-cadherin, and ZO-1 were used for incubation overnight at 4°C. Subsequently, a secondary antibody (Alexa Fluor Plus 594) was added and incubated at room temperature for 1 hour. The tissue was stained with DAPI (Biyuntian) for 5 minutes, the sections were mounted with an antifluorescent quencher, and observed and photographed using a fluorescence microscope.

[0075] 1.7 Experimental Results Numerous studies have already been conducted on the use of BC in disease treatment, and its good biocompatibility and safety have been verified. However, due to the unique anatomical structure and immune environment of the lungs, there has been insufficient research on the use of BC within the lungs. To determine whether BC can be safely used in the lungs, the inventors referred to the maximum intragastric infusion volume in previous studies of oral acute toxicity experiments with BC and, as described in Test Example 1.1 above, set two dosages, 2 mg / kg and 4 mg / kg, to investigate whether the use of BC within the lungs causes damage.

[0076] As shown in the administration scheme in Figure 1A, mice were administered BC at different concentrations via nasal drop for 14 consecutive days, and samples were collected within 24 hours after the last administration. Weight changes in the mice within 14 days (Figure 1B, n=4) were recorded, showing no statistically significant differences in weight changes between the groups. Lung histopathology sections obtained according to Test Examples 1.4 and 1.5 (Figure 1C, n=4, magnification 200x) showed no obvious damage, proliferation, or infiltration of inflammatory cells in the lung interstitium by H&E staining, and no obvious damage to the airways. Furthermore, PAS glycogen staining showed no proliferation of goblet cells or increased mucus secretion. These experimental results indicate that intrapulmonary administration of BC via nasal drop at doses of 2 mg / kg and 4 mg / kg did not cause death, cachexia, or acute lung injury in mice, suggesting that intrapulmonary administration of BC via nasal drop is feasible.

[0077] After confirming the safety and feasibility of intrapulmonary administration of two doses of BC, an HDM-induced mouse asthma model was constructed as shown in the scheme in Test Example 1.2 and Figure 2A, and mouse lung tissue obtained using the methods described in Test Examples 1.4 and 1.5 was tested. In the H&E stained sections (Figure 2B), compared to the modeling group (i.e., the HDM group), the two different dose BC treatment groups (i.e., the HDM + 2 mg / kg BC group and the HDM + 4 mg / kg BC group) showed reduced airway injury, and both the continuity of the airway epithelium and the expression of airway epithelial cell damage and shedding were significantly improved in the treatment group mice compared to the modeling group. In the PAS stained sections (Figure 2B), reduced airway mucus secretion and reduced goblet cell proliferation were also observed in the BC treatment group mice compared to the modeling group mice. In other words, staining of the histopathological sections showed that nasal intrapulmonary administration of BC reliably reduces the expression of asthma-induced airway epithelial injury and decreases mucus secretion in the HDM-induced asthma mouse model.

[0078] Furthermore, ELISA detection of mouse bronchoalveolar lavage fluid (BALF) as described in Test Example 1.3 above showed that the expression levels of asthma type 2 inflammation indicators IL-13 (Figure 2C) and IL-5 (Figure 2D) were both lower in the two different dose BC treatment groups (i.e., the HDM + 2 mg / kg BC group and the HDM + 4 mg / kg BC group) compared to the HDM group, with a statistically significant difference. In particular, the IL-5 expression level in the HDM + 2 mg / kg BC group recovered to the control group level. Surprisingly, the related allermins IL-25, IL-33, and TSLP in epithelial cells also recovered to the control group level in the different dose BC treatment groups (Figures 2E-2G). In other words, the detection of BALF inflammation factors via ELISA revealed that nasal intrapulmonary administration of BC in an HDM-induced asthma mouse model can reduce asthmatic airway inflammation.

[0079] Furthermore, to verify whether airway epithelial cell barrier function damage improved after BC treatment, the inventors detected the expression levels of tight junction proteins and adhesion proteins (E-cadherin, ZO-1, β-catenin) in airway epithelial cells of mouse lung tissue sections using immunofluorescence as described in Test Example 1.6. In the HDM + 4 mg / kg BC group, the expression levels of both tight junction proteins and adhesion proteins in airway epithelial cells recovered to normal levels (Figure 2H and Figure 2I). In addition, the expression levels of each protein were improved in the HDM + 2 mg / kg BC group compared to the HDM group. The above further demonstrates that nasal intrapulmonary administration of BC can effectively reduce airway epithelial damage and decrease the secretion of inflammatory factors in an HDM-induced asthma model.

[0080] This study demonstrated that in a mouse model, BC exhibits good safety and the desired therapeutic effect of reducing airway damage caused by asthma at doses of 2 mg / kg and 4 mg / kg. Based on common conversion methods in the art, the dose in mice is approximately 9.01 times that in humans (calculated assuming a body weight of 60 kg). Therefore, when the bacterial cellulose of the present invention is administered to a 60 kg adult, the applicable dose is predicted to be approximately 0.1 mg to 0.5 mg per kilogram of body weight.

[0081] Example 2: Cell experiment 2.1 Construction and treatment of cellular asthma models BEAS-2B cells were cultured in DMEM / 10% FBS medium and stimulated for 48 hours with 800U HDM (Alutard SQ indoor dust mite allergen preparation 100,000 SQ-U / ml) to model asthma. The control group was not stimulated with HDM. The HDM groups were stimulated for 48 hours with the addition of 800U HDM. 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 and 0.8g of BC, 800U HDM and 1.6g of BC, 800U HDM and 3.2g of BC, and 800U HDM and 6.4g of BC, respectively, for 48 hours. The BC is bacterial cellulose having a diameter of 15 to 35 nanometers and a length of 150 to 1000 nanometers, obtained by treating and polishing cellulose produced from Acetobacter xylinum using the method described above.

[0082] 2.2 CCK8 Cytotoxicity Detection Experiment BEAS-2B cells were inoculated into a 96-well plate and cultured, resulting in a cell density of 1 × 10⁶ per well. 4 The cells were cultured until the cell density reached 60%, and then the DMEM / 10% FBS medium was replaced with DMEM medium, and different concentrations of BC (BC in PBS were 0 mg / L, 3.28 mg / L, 6.56 mg / L, 13.12 mg / L, and 26.24 mg / L, and the BC was bacterial cellulose with a diameter of 15 to 35 nanometers and a length of 150 to 1000 nanometers, obtained by processing and polishing cellulose produced from Acetobacter xylinum in the manner described above) were added and stimulated for 48 hours. After culturing at 37°C and 5% CO2 for 48 hours, the medium in each well was replaced by mixing it with DMEM medium in a 1:10 volume ratio using the reagents from Cell Counting Kit 8 (CCK-8). Next, the cells were cultured in a light-shielding cell incubator for 1 hour and 30 minutes, and the absorbance at 450 nm in each well was measured using a multifunctional enzyme label analyzer. The cell viability was then calculated using the following formula. Cell viability = [Test well OD value - Background OD value] / [Control well OD value - Background OD value] × 100%.

[0083] 2.3 Western blot method Protease inhibitors and protease phosphate inhibitors were added to high-intensity RIPA in a 1:100 ratio, and total cellular proteins were extracted from each group of cells in Test Example 2.1. Proteins were separated on 8% and 12% SDS-PAGE gels and transferred onto PVDF membranes. The PVDF membranes were blocked at room temperature for 8 minutes using a membrane rapid blocking solution, incubated overnight in a refrigerator at 4°C with primary antibodies (Proteintech) for β-catenin and E-cadherin, and then labeled with near-infrared DyLight fluorescent secondary antibody and developed using the Odyssey LI-COR infrared fluorescence imaging system.

[0084] 2.4 Immunofluorescence of Cells Cells from each group in Test Example 2.1 were fixed with 4% paraformaldehyde at room temperature for 10 minutes, ruptured with 0.1% Triton-X100 for 10 minutes, blocked with 5% BSA at room temperature for 1 hour, and incubated overnight in a refrigerator at 4°C with primary antibodies (CST) of ZO-1 and E-cadherin. Subsequently, secondary antibodies (Alexa Fluor Plus 594) were added and incubated at room temperature for 1 hour, stained with DAPI (Biyuntian) diluted 1:1 at room temperature for 2 minutes, and observed and photographed using a confocal microscope.

[0085] 2.5 Experimental Results From the animal experiments in Test Example 1 above, it was found that in an asthma animal model, the use of BC could alleviate asthma symptoms and improve airway epithelial damage caused by asthma. Furthermore, the inventors observed that airway epithelial cells may be the main target cells of BC. Therefore, the following experiment will verify whether BC improves asthma symptoms by acting on airway epithelial cells. First, we chose to construct an asthma model using human bronchial epithelial cell line (BEAS-2B) cells stimulated by HDM. For specific experimental methods, please refer to Test Example 2.1 above.

[0086] Next, in order to select an appropriate stimulating concentration and verify cytotoxicity, the inventors first screened for appropriate concentrations using the CCK8 cytotoxicity experiment described in Test Example 2.2 above. As shown in Figure 3A, BC did not induce airway epithelial cell death at a concentration of 3.28 mg / L.

[0087] Furthermore, to select an appropriate therapeutic concentration, BCs with concentrations of 0.4 g / ml, 0.8 g / ml, 1.6 g / ml, and 3.2 g / ml were selected and treated with 800 U HDM along with the asthma cell model prepared in Test Example 2.1. The effects of different concentrations of BC on the expression levels of representative tight junction and adhesion proteins (β-catenin and E-cadherin) under a concentration gradient were examined using the Western blotting method described in Test Example 2.3. As shown in Figure 3B, 0.4 g / ml and 0.8 g / ml of BC had a good effect on improving HDM-induced epithelial cell damage.

[0088] Furthermore, to verify the ability of different concentrations of BC to improve epithelial barrier damage, the expression status of tight junction proteins and adhesion proteins (ZO-1, E-cadherin) in different groups of cells was examined using the cell immunofluorescence experiment described in Test Example 2.4 above (Figure 3C). As a result, it was found that a concentration of 0.8 g / ml of BC had a superior improving effect on HDM-induced damage. This suggests that, at appropriate therapeutic concentrations, higher concentrations lead to greater therapeutic efficacy.

[0089] From the above test examples, it was found that the bacterial cellulose of this disclosure has good safety, can improve epithelial cell damage, restore epithelial continuity of airway epithelial cells, reduce cell shedding, reduce airway mucus secretion, reduce goblet cell proliferation and thus reduce inflammatory responses, and further improves damage to the epithelial barrier, achieving the effect of treating or preventing airway diseases, especially airway diseases associated with epithelial cell damage (such as asthma), and thus has reliable applicability.

[0090] The above embodiments are illustrative and not limit the scope of this disclosure. Those skilled in the art can modify and alter the above embodiments without departing from the spirit and scope of this disclosure. Accordingly, the scope of protection of this disclosure is defined by the claims attached to this disclosure and is included in the technical content of this disclosure, unless such claims affect the effect and purpose of this disclosure.

Claims

1. The use of a composition for manufacturing a medicine for treating or preventing respiratory tract diseases, The composition comprises bacterial cellulose formed from β-1-4-glucan, The bacterial cellulose used has a diameter of 15 nanometers to 35 nanometers and a length of 100 nanometers to 3000 nanometers.

2. The use according to claim 1, wherein the length-to-diameter ratio of the bacterial cellulose is 2.5 to 86.

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

4. The composition is administered to individuals in need at doses of 1 to 4 times per day. The use according to claim 1, wherein the dose of the composition administered per dose is 0.1 milligrams to 0.5 milligrams of bacterial cellulose per kilogram of body weight.

5. The composition is administered to the individual via nasal or inhalation. The aforementioned nasal administration includes the form of drops or sprays. The use according to claim 4, wherein the inhalation administration includes a nebulizer or a dry powder form.

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

7. The use according to claim 1, wherein the composition further comprises at least one from the group consisting of seasonings, dispersants, wetting agents, lubricants, thickeners, stabilizers, preservatives, antioxidants, antibacterial agents, and colorants.

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

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

10. The use according to claim 9, wherein the aforementioned airway disease is asthma.

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