Use of fiber formed from beta-1-4-glucan for the manufacture of a composition for treating or preventing gastroesophageal reflux disease

Abstract

To provide a composition for treating or preventing gastroesophageal reflux disease.SOLUTION: The present invention provides the use of fibers formed from β-1-4-glucan for producing a composition that treats or prevents gastroesophageal reflux disease, where the fibers are 15-35 nm in diameter and 1.5-3.5 μm in length.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to compositions for treating or preventing gastroesophageal reflux disease, and in particular to the use of fiber formed from β-1-4-glucan to prepare compositions for treating or preventing gastroesophageal reflux disease. [Background technology]

[0002] Gastroesophageal reflux disease (GERD), as the name suggests, is a condition in which gastrointestinal contents are diverted back up into the esophagus, causing discomfort in the stomach, esophagus, throat, and respiratory tract, or damage to the esophageal mucosa. It is primarily related to a loose lower esophageal sphincter (cardia), but other causes of reflux include impaired esophageal emptying or peristalsis, insufficient protective function of the esophageal mucosa, delayed gastric emptying, diaphragmatic hernia, and increased gastric pressure. GERD is a chronic, recurring condition that often presents with discomfort, including chest heat (heartburn), hoarseness or sore throat, difficulty swallowing, hiccups, nausea, dry cough, and flatulence. Complications of GERD include esophageal inflammation (e.g., esophagitis, erosion, ulcers, bleeding, fibrosis, and stricture) and Barrett's esophagus (BE). Clinically, upper gastrointestinal endoscopy can classify erosive esophagitis (EE) due to gastroesophageal reflux disease (GERD) into four grades according to the Los Angeles classification: Grade A, mucosal breaks ≤5mm, not extending into more than two mucosal folds; Grade B, mucosal breaks >5mm, but not extending into more than two mucosal folds; Grade C, mucosal breaks extending into or merging with two mucosal folds, but not exceeding 75% of the circumference of the esophageal tract; and Grade D, mucosal breaks extending into or merging with two mucosal folds, and exceeding 75% of the circumference of the esophageal tract. Summary of the Invention [Problem to be solved by the invention]

[0003] Clinical medications for treating gastroesophageal reflux disease include neutralizing stomach medications such as antacids, protective stomach medications, and medications that promote intestinal peristalsis. Antacids are a common treatment. Unfortunately, however, these medications should not be taken for long periods of time or in large doses. Doing so can over-suppress gastric acid, potentially leading to a rebound in gastric acid secretion. Over-suppression of gastric acid can also impair food digestion and cause abdominal distension. Antacids also have side effects, such as diarrhea caused by magnesium salts and constipation caused by aluminum salts. Long-term use of antacids can also affect the circulatory system and kidney function, potentially increasing the risk of infection. Proton pump inhibitors are the primary medications used to treat gastroesophageal reflux disease (GERD), but their therapeutic use is limited because 6% to 15% of patients with erosive esophagitis, 20% of patients with Barrett's esophagus, and 40% to 50% of patients with non-erosive reflux (those with reflux symptoms only and no mucosal inflammation or damage detected by gastroscopy) do not respond to treatment. Long-term use of proton pump inhibitors carries the risk of complications such as fractures, community-acquired pneumonia, and hospital-acquired refractory clostridial diarrhea, as well as side effects caused by effects on the absorption of vitamins C and B12. [Means for solving the problem]

[0004] In view of the above, the present disclosure provides use of fibers formed from β-1-4-glucan for the manufacture of a composition for treating or preventing gastroesophageal reflux disease, the fibers having a diameter of 15 to 35 nm and a length of 1.5 to 3.5 μm.

[0005] In at least one embodiment of the use of the present disclosure, the gastroesophageal reflux disease is erosive esophagitis of grade A and grade B according to the Los Angeles classification.

[0006] In at least one embodiment of the use of the present disclosure, the length to diameter ratio of the fibers is 60-150.

[0007] In at least one embodiment of the use of the present disclosure, the composition is administered to the individual in a form comprising fiber formed from β-1-4-glucan and a liquid medium, or the composition may be administered to the individual in the form of a frozen tablet.

[0008] In at least one embodiment of the use of the present disclosure, the composition is administered to an individual in need of treating or preventing gastroesophageal reflux disease in 1 to 4 doses per day, each dose of the composition comprising 0.02 to 0.12 g of fiber.

[0009] In at least one embodiment of the use of the present disclosure, the liquid medium is water.

[0010] In at least one embodiment of the use of the present disclosure, the content of fibers is between 0.2% and 1.2% by weight, based on the total weight of the composition.

[0011] In at least one embodiment of the use of the present disclosure, the composition comprises 0.1 mL of water and OD 620 is greater than 0.25 and equal to or less than 1.25, for example, between 0.4 and 1.22.

[0012] In at least one embodiment of the use of the present disclosure, the fiber is formed by fermentation of at least one bacterium selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, and Agrobacterium.

[0013] In at least one embodiment of the use of the present disclosure, the bacterium is at least one of the group consisting of Acetobacter xylinum, Gluconacetobacter hansenii, Gluconacetobacter xylinus, and Gluconacetobacter sacchari.

[0014] In at least one embodiment of the use of the present disclosure, the composition further comprises at least one of the group consisting of organic nutrients, probiotics, drugs, dietary fiber, flavoring agents, dispersants, humectants, lubricants, thickeners, stabilizers, preservatives, antioxidants, antimicrobial agents, and colorants.

[0015] In at least one embodiment of the use of the present disclosure, the composition is administered to an individual in need thereof by oral administration.

[0016] The present disclosure further provides a method for manufacturing a medicament for treating or preventing gastroesophageal reflux disease, comprising administering to an individual in need thereof fiber formed from β-1-4-glucan, said fiber having a diameter of 15 to 35 nm and a length of 1.5 to 3.5 μm.

[0017] The present disclosure further provides a frozen tablet for treating or preventing gastroesophageal reflux disease, comprising fibers formed from β-1-4-glucan, said fibers having a diameter of 15 to 35 nm and a length of 1.5 to 3.5 μm.

[0018] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the gastroesophageal reflux disease is Los Angeles Classification Grade A and Grade B erosive esophagitis.

[0019] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the length to diameter ratio of the fibers is 60-150.

[0020] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the fiber is administered to an individual in need of treating or preventing gastroesophageal reflux disease one to four times daily, with each administration comprising 0.02 to 0.12 g of fiber.

[0021] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, fiber is included in the composition and administered to an individual in need of treating or preventing gastroesophageal reflux disease.

[0022] In at least one embodiment of the methods, compositions and frozen tablets of the present disclosure, the composition is administered to the individual in the form of a frozen tablet.

[0023] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the composition is administered to an individual in a form comprising fiber formed from β-1-4-glucan and a liquid medium.

[0024] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the liquid medium is water.

[0025] In at least one embodiment of the method, composition, and frozen tablet of the present disclosure, the fiber content is 0.2 wt % to 1.2 wt % of the total weight of the composition.

[0026] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the composition comprises 0.1 mL of water and 620 is greater than 0.25 and equal to or less than 1.25, for example, between 0.4 and 1.22.

[0027] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the fibers are formed by fermentation of at least one bacterium selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, and Agrobacterium.

[0028] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the bacterium is at least one member of the group consisting of Acetobacter xylinum, Gluconacetobacter hansenii, Gluconacetobacter xylinus, and Gluconacetobacter sacchari.

[0029] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the composition further comprises at least one of the group consisting of organic nutrients, probiotics, drugs, dietary fiber, flavoring agents, dispersants, humectants, lubricants, thickeners, stabilizers, preservatives, antioxidants, antimicrobial agents, and colorants.

[0030] In at least one embodiment of the methods, compositions, and frozen tablets of the present disclosure, the fiber is administered to an individual in need thereof by oral administration. [Effects of the Invention]

[0031] The present disclosure provides a fiber formed from β-1-4-glucan that effectively treats, improves, alleviates, or prevents gastroesophageal reflux disease and the discomfort caused by it, with excellent efficacy and minimal side effects. DETAILED DESCRIPTION OF THE INVENTION

[0032] Hereinafter, embodiments of the present disclosure will be described with reference to specific specific embodiments, but those skilled in the art can easily understand the scope and effects of the present disclosure from the contents of this specification. However, the embodiments described in this specification are not intended to limit the present disclosure, and the exemplified technical features or ideas can be combined with each other, and the present invention can be implemented or applied in other different embodiments. Each detailed description in this specification can be modified and changed based on various perspectives and applications without departing from the spirit of the present disclosure.

[0033] When a particular element described in this specification is referred to as "comprising," "containing," or "having," it does not exclude other elements, such as elements, compositions, structures, regions, portions, devices, systems, steps, or connections, unless otherwise specified.

[0034] Unless expressly stated otherwise herein, the singular forms "a," "an," and "the" as used herein include the plural forms thereof. Furthermore, the terms "or" and "and / or" as used herein may be used interchangeably.

[0035] The numerical ranges described herein are inclusive and combinable, and any value within a numerical range described herein can be used as a minimum or maximum value to derive subranges, etc. For example, a numerical range of "diameter of 15 to 35 nm" should be understood to include any subrange between the minimum value of 15 nm and the maximum value of 35 nm, such as subranges of 15 to 30 nm, 16 to 35 nm, and 22 to 28 nm, etc. Furthermore, if a numerical value falls within each range described herein (e.g., between the maximum and minimum values), it should be considered to be within the scope of the present disclosure.

[0036] In at least one embodiment of the present disclosure, fibers formed from β-1-4-glucan have a diameter of 15 to 35 nm, for example, about 15 nm, about 16 nm, about 17 nm, about 18 nm, about 19 nm, about 20 nm, about 21 nm, about 22 nm, about 23 nm, about 24 nm, about 25 nm, about 26 nm, about 27 nm, about 28 nm, about 29 nm, about 30 nm, about 31 nm, about 32 nm, about 33 nm, about 34 nm, or about 35 nm. In some embodiments, the fibers of the present disclosure have a length of 1.5 to 3.5 μm, e.g., about 1.5 μm, about 1.6 μm, about 1.7 μm, about 1.8 μm, about 1.9 μm, about 2.0 μm, about 2.1 μm, about 2.2 μm, about 2.3 μm, about 2.4 μm, about 2.5 μm, about 2.6 μm, about 2.7 μm, about 2.8 μm, about 2.9 μm, about 3.0 μm, about 3.1 μm, about 3.2 μm, about 3.3 μm, about 3.4 μm, or about 3.5 μm. In some embodiments of the present disclosure, the fiber diameter is between 15 and 35 nm, and the average fiber length is between 1.5 and 3.5 μm. In at least one embodiment of the present disclosure, all fiber diameters are between 15 and 35 nm.

[0037] The fiber formed from the β-1-4-glucan of the present disclosure can be used to prepare a composition for treating or preventing gastroesophageal reflux disease, and can also be used to treat or prevent gastroesophageal reflux disease by administering the fiber formed from β-1-4-glucan to an individual in need thereof. In some embodiments, the composition of the present disclosure can be, but is not limited to, a pharmaceutical composition. In some embodiments of the present disclosure, gastroesophageal reflux disease refers to erosive esophagitis of grades A to D according to the Los Angeles Classification System, or esophageal reflux disease clinically diagnosed by a physician using methods such as upper gastrointestinal endoscopy (gastroscopy), 24-hour esophageal pH measurement, pH / impedance monitoring, lower esophageal sphincter pressure measurement, barium x-ray imaging, proton pump inhibitor testing, medical interviews, or patient self-administered questionnaires. Grades A and B of erosive esophagitis according to the Los Angeles Classification are generally considered to be mild gastroesophageal reflux disease, and the compositions of the present disclosure are effective in treating or preventing mild gastroesophageal reflux disease, allowing patients taking medication to discontinue their medication, reduce their dosage, or switch to a less potent medication. Even severe gastroesophageal reflux disease, such as Grades C and D of erosive esophagitis according to the Los Angeles Classification, can be treated with the compositions of the present disclosure, which may be used in conjunction with medication, endoscopic surgery, surgical treatment, and other therapies and procedures.

[0038] In at least one embodiment, the fiber formed from the β-1-4-glucan of the present disclosure or a composition thereof is in the form of a frozen tablet, including a dosage form formed through a freeze-drying process, such as a dried tablet. In some embodiments of the present disclosure, the process of at least one of low-temperature freezing, low-temperature, low-pressure air suction, and desorption improves the overall stability of the product, making it less susceptible to deterioration, and the excellent rehydration properties of the produced fiber allow for convenient and rapid use. In some embodiments of the present disclosure, the processes of low-temperature freezing, low-temperature, low-pressure air suction, and desorption may be performed in this order, but it should be understood that the order of the processes is not limited thereto and may be adjusted appropriately depending on the properties of the fiber to be produced. In some embodiments of the present disclosure, the fiber formed from the β-1-4-glucan or a composition thereof does not contain a liquid medium and is in the form of a dry powder, for example, produced by a freeze-drying process.

[0039] In at least one embodiment of the present disclosure, a fiber formed from β-1-4-glucan or a composition thereof can be administered orally directly, for example, but not limited to, in the form of a frozen tablet or a dry powder, to an individual in need of treating or preventing gastroesophageal reflux disease. In some embodiments of the present disclosure, the fiber is broken down by saliva in the mouth and entered the digestive tract upon swallowing.

[0040] In at least one embodiment of the present disclosure, when administering a frozen tablet or dry powder to an individual in need of treating or preventing gastroesophageal reflux disease, the frozen tablet or dry powder can optionally be premixed with a liquid medium to form a composition containing a liquid medium and fiber. In some embodiments, when a composition containing a liquid medium of the present disclosure is orally administered, the composition is in a liquid state, exhibiting good flowability, making it easy for the individual to swallow and preventing the individual from choking. In some embodiments of the present disclosure, the liquid medium may include, but is not limited to, an edible liquid such as water, juice, or tea. In some embodiments of the present disclosure, since the composition obtained by production contains a liquid medium, it is not necessary to premix the fiber produced by the present disclosure with a liquid medium before an individual uses the composition of the present disclosure.

[0041] In at least one embodiment of the present disclosure, the fiber content may be between 0.2 wt% and 1.2 wt% of the total weight of the composition to improve the 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 the present disclosure, if the fiber content is less than 0.2 wt%, the fibers may not provide enough hydroxyl groups, which may affect the surface tension of the liquid medium to some extent. In some embodiments of the present disclosure, if the fiber content is less than 0.2 wt%, the liquid medium and the fibers may aggregate due to cohesive forces, resulting in a phenomenon known as layer separation, which is detrimental to mixing.

[0042] In at least one embodiment of the present disclosure, when the fiber content in the composition is about 0.25% by weight, the fiber, a frozen tablet or dry powder containing the fiber, and water or another liquid medium may be mixed in a single or multiple steps to form a liquid composition from the fiber and the liquid medium, and the frozen tablet or dry powder may absorb the liquid medium and disintegrate to form a liquid composition. In some embodiments of the present disclosure, a small amount of water or another liquid medium may be added in advance to form a thickened liquid from the fiber, frozen tablet or dry powder, and then further water or liquid medium may be added to dilute it into a liquid with better fluidity. For example, in some embodiments of the present disclosure, the fiber may be present in a concentration of about 1.0 wt % in the thickened liquid formed in the first stage, and after one or more additions of water or liquid medium, the fiber concentration may be between 0.1 wt % and 0.5 wt %, e.g., 0.1 wt %, 0.15 wt %, 0.2 wt %, 0.25 wt %, 0.3 wt %, 0.35 wt %, 0.4 wt %, 0.45 wt %, or 0.5 wt %.

[0043] In at least one embodiment, the length to diameter ratio of the fibers produced by the present disclosure can be between 60 and 150, e.g., 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 141, 142, 143, 144, 145, or 150.

[0044] In at least one embodiment, a liquid composition formed by combining a fiber produced according to the present disclosure with water may form a contact angle of about 95° to less than 110° with the surface of Parafilm (Parafilm, Bemis, PM996), e.g., 95.5°, 96°, 96.5°, 97°, 97.5°, 98°, 98.5°, 99°, 99.5°, 100°, 100.5°, 101°, 101.5°, 102°, 102.5°, 103°, 103.5°, 104°, 104.5°, 105°, 105.5°, 106°, 106.5°, 107°, 107.5°, 108°, 108.5°, 109°, or 109.5°.

[0045] In at least one embodiment, a composition comprising 0.2% to 1.2% by weight of fiber of the present disclosure and 0.1 mL of water has an optical density value (OD ) measured at a wavelength of 620 nm (nm). 620 ) is between 0.25 and 1.25. In some embodiments of the present disclosure, OD 620 The lower limit of OD may be 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 0.33, 0.35, 0.37, 0.39, 0.4, 0.41, 0.43, 0.45, 0.5, 0.6, 0.7, or 0.8. 620 The upper limit of OD may be 1.25, 1.24, 1.23, 1.22, 1.21, 1.2, 1.1, 1, 0.9, 0.8, 0.7, 0.6, or 0.5. 620 may be, for example, 0.295, 0.335, 0.435, 0.53, 0.54, 0.55, 0.65, 0.75, 0.76, 0.78, 0.85, 0.88, 0.93, 0.96, 0.98, 1.05, 1.08, 1.13, 1.14, 1.19, 1.215 or 1.225.

[0046] In at least one embodiment, the fibers of the present disclosure are obtained through a fibrillation process from biocellulose formed by one or more microorganisms, and the biocellulose may be composed of D-glucose units linked together in the form of β(1→4) glycosidic bonds, and therefore belongs to the β-1-4-glucan family. In some embodiments of the present disclosure, unlike plant cellulose, the biocellulose has a higher purity.

[0047] In at least one embodiment, the microorganism of the present disclosure may be a bacterium, and the biocellulose may be produced by bacterial culture and fermentation. In some embodiments, the bacterium of the present disclosure may be at least one bacterium selected from the genera Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, Agrobacterium, or any combination thereof. In some embodiments, the bacterium of the present disclosure is at least one bacterium selected from the group consisting of Acetobacter xylinum, Gluconacetobacter hansenii, Gluconacetobacter xylinus, and Gluconacetobacter sacchari. In some embodiments of the present disclosure, Gluconacetobacter xylinus may be selected for use in biocellulose production, but is not limited to this. In some embodiments of the present disclosure, a single bacterial species or multiple bacterial species may be selected for use in biocellulose production, and the selection may be adjusted according to actual needs, without limitation.

[0048] To provide the biocellulose for fiber production of the present disclosure, a culture medium is prepared in advance in a container, and the single or multiple bacterial species are cultured in the container in a static manner for 24 to 96 hours (e.g., 24, 36, 48, 60, 72, 84, or 96 hours) in the culture medium, and the absorbance (wavelength at 620 nm) of the bacterial concentration in the culture medium is controlled to a 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 embodiments of the present disclosure, the pH value of the culture medium 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 embodiments of the present disclosure, the concentration range of the microorganism in the culture medium is 10 2 ~10 5 cells / mL, e.g., approximately 1 x 10 2 pieces / mL, approximately 5×10 2 pieces / mL, approximately 1×10 3 pieces / mL, approximately 5×10 3 pieces / mL, approximately 1×10 4 pieces / mL, approximately 5×10 4 cells / mL or approximately 1 x 10 5 In some embodiments of the present disclosure, the culture temperature is controlled to between 25°C and 30°C, and may be controlled to, for example, about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, or about 30°C. In some embodiments of the present disclosure, the culture of the microorganisms of the present disclosure can be controlled by selecting the absorbance of the bacterial concentration in the culture medium, the pH value of the culture medium, the concentration range of the microorganisms in the culture medium, the culture temperature, or any combination thereof.

[0049] As used herein, the term "static culture" refers to allowing bacteria to form a layered fiber membrane on the surface of the culture medium (i.e., the air-liquid interface) in a nonwoven manner. The container used for static culture may be a flat container with a large culture area, and the height of the container may be relatively low to control the oxygen consumption of the bacteria and further adjust the diameter of the biocellulose. In some embodiments of the present disclosure, the density of the network structure formed by the surface biocellulose in the synthetic fiber membrane is greater and denser than the network structure inside the fiber membrane, and therefore the static culture and culture conditions described above are advantageous for subsequent separation of the interwoven biocellulose.

[0050] As used herein, the term "fiber membrane" refers to a layered structure having a multi-layer network structure in which multiple layers of biocellulose are woven together. In some embodiments of the present disclosure, the thickness of the fiber membrane may be between 20 and 30 μm, such as about 20 μm, about 22 μm, about 24 μm, about 25 μm, about 26 μm, about 28 μm, or about 30 μm. In some embodiments of the present disclosure, the amount of biocellulose per unit area of ​​the fiber membrane is 0.001 to 0.002 g / cm. 2 For example, about 0.0011 g / cm 2 , about 0.0012g / cm 2 , about 0.0013g / cm 2 , about 0.0015g / cm 2 , about 0.0017g / cm 2 , about 0.0018g / cm 2 or approximately 0.0019 g / cm 2 In some embodiments of the present disclosure, the diameter of the biocellulose in the fiber membrane is between 15 and 100 nm, for example, about 15 nm, about 20 nm, about 25 nm, about 30 nm, about 35 nm, about 40 nm, about 45 nm, about 50 nm, about 55 nm, about 60 nm, about 65 nm, about 70 nm, about 75 nm, about 80 nm, about 85 nm, about 90 nm, about 95 nm, or 100 nm.

[0051] In at least one embodiment, the components of the culture medium may include a carbon source, a nitrogen source, and a gel support. 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. The gel support may be selected from, but is not limited to, agar. In some embodiments of the present disclosure, the culture medium may include agar, a carbon source, peptone, and yeast extract, and the weight ratio of the carbon source, peptone, and yeast extract may be 5:1:1 to 4:1:1.

[0052] In at least one embodiment of the present disclosure, the fibrous membrane may be formed by static fermentation of bacteria of the genus Gluconacetobacter in a culture medium containing mannitol, peptone, yeast extract, and agar, and the produced fibrous membrane has a moisture content of greater than 85%, for example, greater than 90%, greater than 92%, or greater than 95%.

[0053] In at least one embodiment, to obtain fibers from which a composition for treating or preventing esophageal reflux disease can be prepared, the fiber membrane is further subjected to a fibrillation treatment, which includes homogenously grinding the fiber membrane to prepare a dispersion, swelling the interwoven biocellulose in the dispersion, and mechanically polishing the swollen biocellulose.

[0054] As used herein, the term "homogenous grinding" refers to obtaining a dispersion by mixing a fiber membrane with a solution and then grinding the mixture with a homogenizer consisting of a fixed outer blade with shear force and a rotatable inner blade with a sawtooth shape.

[0055] In at least one embodiment of the present disclosure, after the dispersion is subjected to the homogenous grinding treatment, other additives may be added to the dispersion to swell the biocellulose woven together in the dispersion. In the present disclosure, the added additives may further include, but are not limited to, other additives commonly used in the art.

[0056] As used herein, the term "swelling treatment" refers to the penetration of a treatment solution into the interior of the biocellulose woven together in the dispersion, thereby reducing the effect of hydrogen bonds between the cellulose, and can reduce energy consumption in the subsequent mechanical polishing treatment without excessive hydrolysis of the biocellulose. In some embodiments of the present disclosure, the synergistic effect of the shear force of mechanical polishing in combination with the shear force of mechanical polishing breaks the glycosidic bonds of the biocellulose, fibrillates the biocellulose, increases the specific surface area of ​​the cellulose, exposes more hydroxyl groups, and improves the hydrophilicity and biocompatibility of the biocellulose.

[0057] In at least one embodiment, the treatment liquid of the present disclosure may be at least one selected from the group consisting of an alkaline solution, an inorganic salt solution, and an ionic liquid aqueous solution. In some embodiments of the present disclosure, the alkali forming the alkaline solution may include at least one selected from the group consisting of potassium hydroxide, sodium hydroxide, and lithium hydroxide. In some embodiments of the present disclosure, the inorganic salt may be at least one selected from the group consisting of urea, zinc chloride, thiourea, calcium chloride, and magnesium chloride. In some embodiments of the present disclosure, the ionic liquid may be 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 dialkylimidazoles.

[0058] As used herein, "mechanical polishing" refers to the process of diluting the dispersion with water and then polishing it in a horizontal ball mill to fibrillate the interwoven biocellulose in the dispersion and form fibers with a diameter of 15-35 nm and a length of 1.5-3.5 μm. The content of biocellulose used in mechanical polishing ranges from about 0.1 wt% to about 0.5 wt%, e.g., about 0.15 wt%, about 0.2 wt%, about 0.25 wt%, about 0.3 wt%, about 0.35 wt%, about 0.4 wt%, or about 0.45 wt% of the total weight of the dispersion. The desired fibers are then obtained by purifying the swollen and mechanically polished dispersion using known methods, including neutralization and desalination, for example, by using semipermeable membrane dialysis to separate salts from the dispersion.

[0059] In at least one embodiment of the present disclosure, the biocellulose after polishing has a high specific surface area, which may result in more pronounced electrostatic effects, van der Waals forces, or hydrogen bonding between cellulose particles, making aggregation more likely to occur. Therefore, in some embodiments, the present disclosure may further include, after mechanical polishing, treating the polished dispersion with ultrasonic vibration to disaggregate the biocellulose aggregates, and optionally lyophilizing the dispersion as needed.

[0060] In at least one embodiment, the composition of the present disclosure may contain fiber formed from β-1-4-glucan and other substances, and the fiber may be in the form of a frozen tablet or dry powder and may form a composition with other substances. In some embodiments, the composition of the present disclosure may further contain at least one of the group consisting of organic nutrients, probiotics, drugs, dietary fiber, flavorings, dispersants, humectants, lubricants, thickeners, stabilizers, preservatives, antioxidants, antibacterial agents, and colorants, and there is no negative effect between the fiber of the present disclosure and each of the above ingredients. In some embodiments, the fiber of the present disclosure may create a synergistic effect with the above ingredients.

[0061] In at least one embodiment, the organic nutrients of the present disclosure include an extract extracted from a culture medium when the microorganism is statically cultured. In some embodiments of the present disclosure, the seasoning agent includes a sweetener and / or a flavoring. In some embodiments of the present disclosure, the probiotics include bacteria of the genus Enterococcus, Lactobacillus, Bacillus, Clostridium, Lactococcus lactis, or the like. lactis, Leuconostoc, Pediococcus, Carnobacterium, Vagococcus, Tetragenococcus, Bifidobacterium, Atopobium, Weissella, Abiotrophia, Granulicatella, Oenococcus, Paralactobacillus, and the like, and Saccharomyces boulardii, and any combination thereof. In some embodiments of the present disclosure, the active ingredient may be selected from Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus rhamnosus, Bifidobacterium longum, and any combination thereof.

[0062] TIFF0007791770000001.tif78169

[0063] In some embodiments of the present disclosure, fiber formed from β-1-4-glucan or a composition containing the formed fiber is administered when the onset of symptoms is predictable or before the onset of symptoms, thereby achieving a preventative and protective effect. For example, the composition of the present disclosure may be in the form of a frozen tablet and administered to an individual in need of treatment or prevention of gastroesophageal reflux disease in one to four doses per day, with each frozen tablet containing 0.02 to 0.12 g of fiber. In some embodiments of the present disclosure, when fiber formed from β-1-4-glucan is directly administered to an individual in need of treatment or prevention of gastroesophageal reflux disease in one to four doses per day, with each dose containing 0.02 to 0.12 g of fiber.

[0064] In some embodiments of the present disclosure, the symptoms may be alleviated by administering fiber formed from β-1-4-glucan or a composition containing the formed fiber at or after the onset of the symptoms. In some embodiments of the present disclosure, the mode of administration is as described above.

[0065] In at least one embodiment of the present disclosure, fiber formed from β-1-4-glucan or a composition containing the formed fiber may be orally administered twice daily, 1 to 12 hours apart, for example, at intervals of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 hours, to treat or alleviate the symptoms. In some embodiments of the present disclosure, fiber formed from β-1-4-glucan or a composition containing the formed fiber may be administered before meals, after meals, or before bedtime. In one embodiment, fiber formed from β-1-4-glucan or a composition containing the formed fiber may be orally administered three times daily, 4 to 8 hours apart. If necessary, more than three doses, for example, four doses, may be administered to achieve more pronounced symptomatic relief.

[0066] The present disclosure is further illustrated in the following examples, which, however, are not intended to limit the scope of the disclosure. [Example]

[0067] Evaluation and Diagnosis of Gastroesophageal Reflux Disease Doctors diagnosed patients with gastroesophageal reflux disease using methods such as upper gastrointestinal endoscopy (gastroscopy), 24-hour esophageal pH measurement, pH / impedance monitoring, lower esophageal sphincter pressure measurement, barium X-ray, proton pump inhibitor test, medical interview, patient self-questionnaire, etc. In the following examples, patients with gastroesophageal reflux disease were recruited and used.

[0068] Evaluation of the symptom-relieving effects of fiber derived from β-1-4-glucan After completing the study, patients answered the following question on a 7-point balanced scale: "Compared to before the study, how would you rate the level of relief of your gastroesophageal reflux disease symptoms? Typical symptoms include: chest heat, acid reflux; atypical symptoms include non-cardiac chest pain, difficulty swallowing, foreign body sensation in the throat, nausea, persistent cough, asthma, hoarseness, sore throat, etc." The effect of fiber formed from beta-1-4-glucan on symptom relief was assessed based on the patient's response. 7-point balance scale: Noticeable reduction Moderate relief Slightly reduced · Unchanged Somewhat strict ·Moderate weight ·Remarkable weight

[0069] Among these, if the patient responded that the symptoms were significantly alleviated, moderately alleviated, or slightly alleviated, the test was evaluated as effective.

[0070] Example 1

[0071] Test Method The patients were orally administered a single dose of a composition containing 0.2% by weight of fiber formed from β-1-4-glucan, the remainder being water, each day before lunch and dinner.

[0072] Example 1 A 60-year-old female gastroesophageal reflux disease patient complained of symptoms once or twice a week. The fiber-containing composition was orally administered daily using the test method described above over a 4.5-month period. When the patient answered the questions on a 7-point balance scale, the results indicated that the product was effective, and that after taking the product, she no longer experienced discomfort from gastroesophageal reflux disease, and there were no adverse effects or side effects.

[0073] Case 2 A 42-year-old female gastroesophageal reflux disease patient complained of symptoms once or twice a week. The fiber-containing composition was orally administered daily using the above test method over a two-month period. When the patient answered the above questions on a 7-point balance scale, the results indicated that the product was effective, and that after taking the product, she no longer experienced discomfort from gastroesophageal reflux, and there were no adverse effects or side effects.

[0074] Example 2

[0075] Test Method When symptoms of gastroesophageal reflux occur, the patient immediately orally administers a single dose of a composition containing 0.2% by weight of fiber formed from β-1-4-glucan, the balance being water.

[0076] Example 1 A 59-year-old male patient with gastroesophageal reflux disease was orally administered the composition containing the fiber using the above test method, and the test period lasted six months. When the patient answered the above questions on a 7-point balance scale, the results showed that the composition was effective and had no adverse effects or side effects.

[0077] Case 2 A 42-year-old female patient with gastroesophageal reflux disease was orally administered the composition containing the fiber using the above test method, and the test period lasted for four months. When the patient answered the above questions on a 7-point balance scale, the results showed that the composition was effective and had no adverse effects or side effects.

[0078] Case 3 A 59-year-old female gastroesophageal reflux disease patient complained of constant heartburn and acid reflux. The patient orally administered the fiber-containing composition using the above test method, and the test period lasted for three months. When the patient answered the above questions on a 7-point balance scale, the results showed that the product was effective and had no adverse effects or side effects.

[0079] Case 4 A 26-year-old male patient with gastroesophageal reflux disease (GERD) complained of experiencing typical symptoms of GERD every week (including chest heat and nausea). When symptoms of GERD appeared, the patient orally administered the composition of Example 1 for one month, taking it whenever symptoms arose within that period. When the patient answered the above questions on a 7-point balanced scale, the results indicated that the composition was effective and had no adverse effects or side effects.

[0080] Case 5 The patient was a 38-year-old male with gastroesophageal reflux disease (GERD). He complained that his GERD symptoms were frequent, occurring at least 1-3 times per week. At the start of the study, when GERD symptoms occurred, the patient was orally administered 1-2 doses of the composition of Example 1. This was continued for one week, and the patient was to take the composition as soon as symptoms arose within that period. When the patient answered the above questions on a 7-point balance scale, the results indicated that the composition was effective, and that symptoms were immediately alleviated within 5 minutes of taking the composition, indicating a significant effect. After the above test, a further test was conducted for three weeks in which the patient was orally administered two doses of the composition of Example 1 every day (choose two from before lunch, before dinner, and before bed). After the test, the patient answered the questions on a seven-point balance scale, and the results showed that the treatment was effective. The patient also reported that only one gastroesophageal reflux symptom occurred during the three-week test period, and no gastroesophageal reflux symptoms were reported within one month after the test ended.

[0081] Case 6 A 41-year-old female gastroesophageal reflux disease patient reported frequent gastroesophageal reflux symptoms, occurring at least once or twice a week. The patient regularly took antacids as prescribed by her doctor, but the symptoms recurred when she stopped taking them. The patient participated in the study of the present disclosure, stopped taking antacids, and was orally administered a single dose of the composition of Example 1 when gastroesophageal reflux symptoms recurred. When the patient answered the questions on a 7-point balance scale, the results indicated that the composition was effective and that symptoms were immediately relieved 5 to 10 minutes after taking the composition, indicating that it could be used in place of antacids.

Claims

1. A pharmaceutical composition for treating or preventing gastroesophageal reflux disease, comprising: comprising a plurality of fibers formed from β-1-4-glucan; The fibers are obtained from biocellulose, The biocellulose is produced by bacterial fermentation, the bacterium is at least one selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, and Agrobacterium; the fibers have a diameter of 15 to 35 nm and an average length of 1.5 to 3.5 μm; the fiber is administered orally in an effective amount one to four times daily; each administered dose comprising 0.02 to 0.12 g of the plurality of fibers; The pharmaceutical composition, wherein the gastroesophageal reflux disease is erosive esophagitis of grade A and grade B according to the Los Angeles classification.

2. 2. The pharmaceutical composition of claim 1, wherein the fiber has a length to diameter ratio of 60 to 150.

3. 10. The pharmaceutical composition of claim 1, administered to an individual in need of treating or preventing gastroesophageal reflux disease.

4. 4. The pharmaceutical composition of claim 3, which is administered to the individual in the form of a frozen tablet.

5. 4. The pharmaceutical composition of claim 3, wherein the composition is administered to the individual in a form consisting of a plurality of fibers formed from the β-1-4-glucan and a liquid medium.

6. 6. The pharmaceutical composition of claim 5, wherein the liquid medium is water.

7. The pharmaceutical composition according to claim 5, wherein the content of said fiber is 0.2% by weight to 1.2% by weight based on the total weight of said pharmaceutical composition.

8. containing 0.1 mL of water, Also, O.D. ６２０ The pharmaceutical composition of claim 7, wherein is greater than 0.25 and less than or equal to 1.

25.

9. Said OD ６２０ The pharmaceutical composition according to claim 8, wherein is 0.4 to 1.

22.

10. 2. The pharmaceutical composition according to claim 1, wherein the bacterium is at least one selected from the group consisting of Gluconacetobacter hansenii, Gluconacetobacter xylinus, and Gluconacetobacter sacchari.

11. 4. The pharmaceutical composition of claim 3, further comprising at least one of the group consisting of organic nutrients, probiotics, drugs, dietary fiber, flavoring agents, dispersants, humectants, lubricants, thickeners, stabilizers, preservatives, antioxidants, antibacterial agents, and colorants.

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