Compositions comprising fibers formed from beta-1-4-glucan

Abstract

Use of a fibre formed from beta-1-4-glucan in the preparation of a composition for the treatment or prevention of diarrhoea, constipation or irritable bowel syndrome, wherein the fibre has a diameter of 15 to 35 nanometres and a length of 1.5 micrometres to 3.5 micrometres. Also provided is a method of using a fibre formed from beta-1-4-glucan for the treatment or prevention of diarrhoea, constipation or irritable bowel syndrome.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to a composition for treating or preventing diarrhea, constipation or irritable bowel syndrome, and in particular to the use of a fiber formed of β-1-4-glucan in the preparation of a composition for treating or preventing diarrhea, constipation or irritable bowel syndrome. BACKGROUND

[0002] Irritable bowel syndrome (IBS) is a functional bowel disorder of the gastrointestinal tract, such as recurrent abdominal pain and discomfort associated with bowel changes, diarrhea, constipation or a combination thereof, and the symptoms are usually long-term, which can last for months or even years. Depending on the condition of diarrhea or constipation, it can be classified into four types: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C), mixed IBS (IBS-M) and unsubtyped IBS (IBS-U). Although irritable bowel syndrome is a common functional gastrointestinal disease, its cause is still unknown so far. Patients with irritable bowel syndrome can experience various symptoms such as diarrhea, constipation, abdominal pain, abdominal distension, excessive bloating, distension, persistent urge to defecate, urgency to defecate, incontinence, a feeling of incomplete emptying, a feeling of tension with bowel movements, hard or lumpy stools, or even no bowel movements at all. Clinically, drugs or adjuvants for treating, relieving or preventing irritable bowel syndrome include fecal volume increasing agents (such as dietary fiber), antidiarrheal agents, laxatives, antispasmodic agents, serotonin agonists or antagonists, antidepressants, selective serotonin reuptake inhibitors, antibiotics and lactic acid bacteria, etc. However, the mechanisms of action of various drugs or adjuvants for irritable bowel syndrome are not clear, and the effects are limited, and even have side effects. For example, tricyclic antidepressants can alleviate the symptoms of irritable bowel syndrome and reduce pain, but can cause drowsiness and constipation; alosetron, a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, can reduce intestinal motility and relieve intestinal pain, but can cause severe constipation and ischemic enteritis; linaclotide and lubiprostone can treat constipation-predominant irritable bowel syndrome, but can cause diarrhea. Therefore, the use of various known drugs or adjuvants must be carefully evaluated for the patient's tolerance to side effects, and the dose needs to be controlled or adjusted according to the actual situation of the patient, which is inconvenient in clinical practice.

[0003] Since current drugs for irritable bowel syndrome have many side effects on patients, they produce other uncomfortable symptoms in response to irritable bowel syndrome, and physicians often need to spend more time considering the combination and dosage control of drugs when diagnosing and treating because of the side effects of drugs on patients. Therefore, there is still an urgent need to develop a safe and effective drug for treating, relieving or preventing irritable bowel syndrome. SUMMARY

[0004] The present disclosure provides use of a fiber formed of β-1-4-glucan in the preparation of a composition for treating or preventing diarrhea, constipation or irritable bowel syndrome, wherein the fiber has a diameter of 15 nm to 35 nm and a length of 1.5 μm to 3.5 μm.

[0005] In at least one embodiment of the use of the present disclosure, the irritable bowel syndrome is constipation-predominant irritable bowel syndrome (IBS-C), diarrhea-predominant irritable bowel syndrome (IBS-D), mixed irritable bowel syndrome (IBS-M), or unclassified irritable bowel syndrome (IBS-U).

[0006] In at least one embodiment of the use of the present disclosure, the aspect ratio of the fiber is 60 to 150.

[0007] In at least one embodiment of the use of the present disclosure, the composition is administered to an individual in need of treatment or prevention of diarrhea, constipation or irritable bowel syndrome in a dose of 1 to 4 times a day, and the dose of the lyophilized tablet for each administration contains 0.02 g to 0.12 g of the fiber.

[0008] In at least one embodiment of the use of the present disclosure, the composition can be administered to an individual in the form of a fiber formed of β-1-4-glucan and a liquid medium, or the composition is administered to an individual in the form of a lyophilized tablet.

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

[0010] In at least one embodiment of the use of the present disclosure, the content of the fiber is 0.2 wt% to 1.2 wt% based on the total weight of the composition.

[0011] In at least one embodiment of the use of the present disclosure, the composition includes 0.1 mL of water, and the OD 620 is greater than 0.25 to 1.25, such as between 0.4 to 1.22.

[0012] In at least one embodiment of the use of the present disclosure, the fiber is fermented from at least one bacteria 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 bacteria is at least one selected from 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 selected from the group consisting of organic nutrients, probiotics, drugs, dietary fibers, flavoring agents, dispersing agents, wetting agents, lubricants, thickening agents, stabilizers, preservatives, antioxidants, antibacterial agents, and coloring agents.

[0015] In at least one embodiment of the use of the present disclosure, the composition is administered to a subject in need thereof orally.

[0016] The present disclosure also provides a method for treating or preventing diarrhea, constipation, or irritable bowel syndrome, comprising administering to a subject in need thereof a fiber formed from β-1-4-glucan, wherein the fiber has a diameter of 15 nm to 35 nm and a length of 1.5 μιη to 3.5 μιη.

[0017] In at least one embodiment of the method of the present disclosure, the fiber is administered to a subject in need of treatment or prevention of diarrhea, constipation, or irritable bowel syndrome in a composition.

[0018] In at least one embodiment of the method of the present disclosure, the composition can be administered to a subject in a form consisting of the fiber formed from β-1-4-glucan and a liquid medium, or the composition is administered to a subject in a form of a lyophilized tablet.

[0019] In at least one embodiment of the method of the present disclosure, the liquid medium is water.

[0020] The present disclosure further provides a lyophilized tablet for treating or preventing diarrhea, constipation, or irritable bowel syndrome, comprising fibers formed from β-1-4-glucan, wherein the fibers have a diameter of 15 nm to 35 nm and a length of 1.5 μm to 3.5 μm.

[0021] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the irritable bowel syndrome is constipation-predominant irritable bowel syndrome (IBS-C), diarrhea-predominant irritable bowel syndrome (IBS-D), mixed irritable bowel syndrome (IBS-M), or unclassified irritable bowel syndrome (IBS-U).

[0022] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the aspect ratio of the fibers is 60 to 150.

[0023] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the fibers are administered to an individual in need of treatment or prevention of diarrhea, constipation, or irritable bowel syndrome in an amount of 0.02 g to 0.12 g per administration, 1 to 4 times a day.

[0024] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the fibers are present in an amount of 0.2 wt% to 1.2 wt% based on the total weight of the composition.

[0025] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the composition comprises 0.1 mL of water, and the OD 620 is greater than 0.25 to 1.25, such as between 0.4 to 1.22.

[0026] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the fibers are fermented from at least one bacteria selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter, and Agrobacterium.

[0027] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the bacteria are at least one of the group consisting of Acetobacter xylinum, Gluconacetobacter hansenii, Gluconacetobacter xylinus, and Gluconacetobacter sacchari.

[0028] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the composition further comprises at least one of the group consisting of organic nutrients, probiotics, drugs, dietary fibers, flavoring agents, dispersing agents, wetting agents, lubricants, thickening agents, stabilizers, preservatives, antioxidants, antibacterial agents, and coloring agents.

[0029] In at least one embodiment of the methods, compositions, and lyophilized tablets of the present disclosure, the fiber is administered orally to the individual in need thereof.

[0030] The present disclosure effectively treats, ameliorates, relieves, or prevents discomfort caused by diarrhea, constipation, and irritable bowel syndrome, etc. by the fiber formed of β-1-4-glucan, and has excellent effects with almost no side effects. DETAILED DESCRIPTION

[0031] The scope and effects of the present disclosure can be easily understood by those skilled in the art of the present disclosure based on the contents described herein. However, the specific embodiments described herein are not intended to limit the present disclosure, and each of the technical features or schemes described herein can be combined with each other, and the present disclosure can be implemented or applied by other different embodiments, and each of the details described herein can be changed or modified according to different views and applications without departing from the present disclosure.

[0032] As used herein, the terms "comprise" or "comprising," or "include" or "including," or "have" or "has" or "contain" or "containing," or "consist of" or "consisting of" when used in this disclosure, specify the presence of stated features, integers, steps, or components thereof, but do not preclude the presence or addition of one or more other features, integers, steps, components, or groups thereof.

[0033] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. Also, the meaning of "or" used in the context of this disclosure is that of the logical operator "and / or," unless the context clearly dictates otherwise.

[0034] The numerical ranges recited herein are inclusive and combinable, any numerical range recited herein is inclusive of the maximum and minimum values recited, and any numerical range recited herein is inclusive of any sub-range falling within the range; for example, a range of "15 to 35 nanometers in diameter" can be interpreted to include any sub-range between the minimum of 15 nanometers and the maximum of 35 nanometers, for example, 15 nanometers to 30 nanometers, 16 nanometers to 35 nanometers, and 22 nanometers to 28 nanometers, etc.; and, if a range is recited herein to fall within a range (for example, between a maximum and a minimum), it is to be construed to be included in the range of the disclosure.

[0035] In at least one embodiment of the disclosure, the fibers formed from beta-1-4-glucan have 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 embodiments, the fibers of the disclosure have a length of 1.5 micrometers to 3.5 micrometers, for example, about 1.5 micrometers, about 1.6 micrometers, about 1.7 micrometers, about 1.8 micrometers, about 1.9 micrometers, about 2.0 micrometers, about 2.1 micrometers, about 2.2 micrometers, about 2.3 micrometers, about 2.4 micrometers, about 2.5 micrometers, about 2.6 micrometers, about 2.7 micrometers, about 2.8 micrometers, about 2.8 micrometers, about 2.9 micrometers, about 3.0 micrometers, about 3.1 micrometers, about 3.2 micrometers, about 3.3 micrometers, about 3.4 micrometers, or about 3.5 micrometers. In some embodiments of the disclosure, the fibers have a diameter of 15 nanometers to 35 nanometers and an average length of 1.5 micrometers to 3.5 micrometers. In at least one embodiment of the disclosure, the fibers have a diameter of 15 nanometers to 35 nanometers.

[0036] The fibers formed from beta-1-4-glucan in the disclosure have use in the preparation of a composition for the treatment or prevention of diarrhea, constipation, or irritable bowel syndrome, and can also be used to treat or prevent irritable bowel syndrome, including administering the fibers formed from beta-1-4-glucan to an individual in need thereof. In some embodiments, the composition of the disclosure can be a pharmaceutical composition, without limitation. In some embodiments of the disclosure, the irritable bowel syndrome can be diarrhea-predominant irritable bowel syndrome (IBS-D), constipation-predominant irritable bowel syndrome (IBS-C), mixed irritable bowel syndrome (IBS-M), or un-subtyped irritable bowel syndrome (IBS-U).

[0037] In at least one embodiment of the present disclosure, the fiber formed from beta-1-4-glucan or composition thereof is in the form of a lyophilized tablet, including a dosage form formed after a lyophilization process, such as in the form of a dry tablet. In some embodiments of the present disclosure, the overall product can be processed by at least one of a freezing process, a low-temperature and low-pressure air pumping process, and a desorption process to improve the stability of the product and to prevent deterioration, and the excellent rehydration of the fiber formed can facilitate rapid administration to a user. In some embodiments of the present disclosure, the product can be sequentially processed by a freezing process, a low-temperature and low-pressure air pumping process, and a desorption process, but it is understood that the order of the processes can be appropriately adjusted depending on the characteristics of the fiber to be formed. In some embodiments of the present disclosure, the fiber formed from beta-1-4-glucan or composition thereof does not include a liquid medium, but is in the form of a dry powder, such as that formed by a lyophilization process.

[0038] In at least one embodiment of the present disclosure, a subject in need of treatment or prevention of diarrhea, constipation, or irritable bowel syndrome can orally administer the fiber formed from beta-1-4-glucan or composition thereof, such as in the form of a lyophilized tablet or a dry powder, without limitation. In some embodiments of the present disclosure, the fiber can be disintegrated by saliva in the mouth and enter the gastrointestinal tract by swallowing.

[0039] In at least one embodiment of the present disclosure, when the lyophilized tablet or dry powder is administered to a subject in need of treatment or prevention of diarrhea, constipation, or irritable bowel syndrome, the lyophilized tablet or dry powder can be optionally mixed with a liquid medium to form a composition including the liquid medium and the fiber. In some embodiments, when the composition of the present disclosure including the liquid medium is orally administered, the composition is in a liquid state, thereby having good flowability, facilitating drinking by the subject, and simultaneously preventing possible choking by the subject. In some embodiments of the present disclosure, the liquid medium can include an edible liquid, such as water, juice, tea, etc., but is not limited thereto. In some embodiments of the present disclosure, the prepared composition already includes the liquid medium, and thus the subject does not need to mix the fiber formed in the present disclosure with the liquid medium before using the composition of the present disclosure.

[0040] In at least one embodiment of the present disclosure, the content of the fiber can be between 0.2 wt% and 1.2 wt% based on the total weight of the composition, so as to increase the dispersion rate thereof. For example, the content of the fiber can 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, when the content of the fiber is less than 0.2 wt%, the fiber can not be able to provide sufficient hydroxyl groups, thus affecting the surface tension of the liquid medium to some extent. In some embodiments of the present disclosure, when the content of the fiber is less than 0.2 wt%, the liquid medium and the fiber can be affected by cohesion and thus agglomerate, resulting in stratification and adversely affecting mixing.

[0041] In at least one embodiment of the present disclosure, when the content of the fiber in the composition is about 0.25 wt%, the liquid medium can be added in a single addition or in multiple stages, for example, the prepared fiber, its lyophilized ingot or dry powder can be mixed with water or other liquid medium, so that the fiber forms a liquid composition, and the lyophilized ingot or dry powder disintegrates to form a liquid composition. In some embodiments of the present disclosure, a small amount of water or other liquid medium can be added first, so that the fiber, lyophilized ingot or dry powder forms a thick liquid, and then water or liquid medium is added to further dilute the liquid to better flowability. For example, in some embodiments of the present disclosure, the content of the fiber in the thick liquid formed in the first stage can be about 1.0 wt%, and after one or more additions of water or liquid medium, the content of the fiber can be between 0.1 wt% and 0.5 wt%, for example, it can be 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%.

[0042] In at least one embodiment, the aspect ratio of the fiber prepared by the present disclosure can be between 60 and 150, for example, it can be 60, 65, 66, 67, 68, 69, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 141, 142, 143, 144, 145, or 150.

[0043] In at least one specific embodiment, the liquid composition formed by mixing the fibers prepared in the present invention with water can form a contact angle of about 95° to less than 110° with the surface of a sealing wax film (Parafilm, Bemis Company, PM996), for example, 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°.

[0044] In at least one embodiment, the optical density (OD) of a composition comprising 0.2 to 1.2 wt% of fiber and 0.1 ml of water at a wavelength of 620 nanometers (nm) is 620 ) is between 0.25 and 1.25. In some specific embodiments of the present disclosure, OD 620 The lower limit value of 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; in some specific embodiments of the present disclosure, OD 620 The upper limit value 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. In some specific embodiments of the present disclosure, the above-mentioned OD 620 The value of can 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.

[0045] In at least one embodiment, the fibers disclosed herein are obtained by defibrillating biocellulose produced by one or more microorganisms. Biocellulose is composed of D-glucose linked together by β(1→4) glycosidic bonds, and is therefore a β-1-4-glucan. In some embodiments of the present disclosure, biocellulose has a higher purity than plant cellulose.

[0046] 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 bacteria of the present disclosure may be selected from 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 biocellulose production, but is not limited thereto. In some embodiments of the present disclosure, a single strain or multiple strains may be selected for biocellulose production, and the selection may be adjusted according to actual needs without limitation.

[0047] In order to provide biocellulose for preparing the fibers of the present invention, a container containing a culture medium may be prepared, and the aforementioned single bacterial species or multiple bacterial species may be cultured in a static manner in the container containing the culture medium for 24 to 96 hours (e.g., 24 hours, 36 hours, 48 ​​hours, 60 hours, 72 hours, 84 hours, 96 hours), and the absorbance value (wavelength of 620 nm) of the bacterial concentration in the culture medium is controlled to be in the range of 0.005 to 0.01, for example, about 0.005, about 0.006, about 0.010, about 0.011, about 0.012, about 0.013, about 0.014, about 0.015, about 0.016, about 0.017, about 0.018, about 0.019, about 0.020, about 0.021, about 0.022, about 0.023, about 0.024, about 0.025, about 0.026, about 0.027, about 0.028, about 0.029, about 0.030, about 0.031, about 0.032, about 0.034, about 0.036, about 0.037, about 0.038, about 0.039, about 0.040, about 0.041, about 0.042, about 0.043, about 0.044, about 0.045, about 0.046, about 0.047, about 0.048, about 0.049, about 0.050, 0.0 0.07, 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 in an acidic environment, including a pH value between 0.5 and 6.5, such as 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 microorganisms in the culture medium is controlled in the range of 10 2 to 10 5 / ml, such as about 1×10 2 / ml, about 5×10 2 / ml, about 1×10 3 / ml, about 5×10 3 / ml, about 1×10 4 / ml, about 5×10 4 / ml or about 1×10 5 / ml; in some embodiments of the present disclosure, the culture temperature can be controlled between 25°C and 30°C, such as about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, or about 30°C. In some embodiments of the present disclosure, the absorbance value of the bacterial concentration in the culture solution, the pH value of the culture solution, the concentration range of the microorganisms in the culture solution, the culture temperature, or any combination thereof can be selected to control the culture of the microorganisms of the present disclosure.

[0048] As used herein, the "static culture" refers to allowing bacteria to form a layered fiber membrane on the surface of the culture solution (i.e., the gas-liquid interface) in a non-woven manner. In addition, the container used for static culture can be a flat container with a wide culture area, so as to control the oxygen consumption of bacteria through a lower container height, thereby achieving the regulation of the diameter of the biocellulose. In some specific embodiments of the present disclosure, since the network structure formed by the biocellulose at the surface of the synthetic fiber membrane has a greater density and is denser than the network structure inside the fiber membrane, the static culture and culture conditions can facilitate the subsequent separation of the interwoven biocellulose.

[0049] As used herein, the "fiber membrane" refers to a layered material interwoven by multiple biocelluloses and having a multi-layered network structure. In some specific embodiments of the present disclosure, the thickness of the fiber membrane may be between 20 microns and 30 microns, such as about 20 microns, about 22 microns, about 24 microns, about 25 microns, about 26 microns, about 28 microns or about 30 microns. In some specific embodiments of the present disclosure, the amount of biocellulose per unit area of ​​the fiber membrane is between 0.001 g / cm2 and 0.002 g / cm2, such as about 0.0011 g / cm2, about 0.0012 g / cm2, about 0.0013 g / cm2, about 0.0015 g / cm2, about 0.0017 g / cm2, about 0.0018 g / cm2 or about 0.0019 g / cm2. In some specific embodiments of the present disclosure, the diameter of the biocellulose in the fiber membrane is between 15 nm and 100 nm, such as 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.

[0050] In at least one embodiment, the ingredients in the culture solution can include a carbon source, a nitrogen source, and a gel support, wherein the carbon source can include at least one sugar or sugar alcohol such as mannitol, glucose, molasses, etc.; the nitrogen source can include peptone, yeast extract, or a combination thereof; and the gel support can be selected from agar, without limitation. In some embodiments of the present disclosure, the culture solution can include agar, a carbon source, peptone, and yeast extract, wherein the weight ratio of the carbon source, peptone, and yeast extract can be 5:1:1 to 4:1:1.

[0051] In at least one embodiment of the present disclosure, the fibrous membrane can be produced by static fermentation of bacteria of the genus Gluconacetobacter in a culture solution including mannitol, peptone, yeast extract, and agar, wherein the produced fibrous membrane has a water content of greater than 85%, such as greater than 90%, greater than 92%, or greater than 95%.

[0052] To obtain a fiber that can be used to prepare a composition for treating or preventing diarrhea, constipation, or irritable bowel syndrome, in at least one embodiment, the fibrous membrane is further subjected to a defibrillation process, which includes homogenously pulverizing the fibrous membrane to produce a dispersion, and then further swelling the biocellulose interwoven with each other in the dispersion, and mechanically grinding the swollen biocellulose.

[0053] As used herein, the "homogenous pulverization" is a pulverization process performed by mixing the fibrous membrane with a solution and then using a homogenizer composed of a fixed outer knife having a shearing force and an inner knife having a saw blade shape and being rotatable to produce a dispersion.

[0054] In at least one embodiment of the present disclosure, after the dispersion is subjected to the aforementioned homogenous pulverization process, other additives can be further added to the dispersion to swell the biocellulose interwoven with each other in the dispersion. The additives added in the present disclosure can include other additives commonly used in the art, without limitation.

[0055] As used herein, the "swelling" includes weakening the hydrogen bonding between the celluloses by allowing a treatment solution to penetrate into the biocellulose interwoven with each other in the dispersion, without causing excessive hydrolysis of the biocellulose, thereby reducing the energy consumption in the subsequent mechanical grinding process. In some embodiments of the present disclosure, the glycosidic bonds of the biocellulose can be broken by the synergistic effect of the shearing force generated in combination with the mechanical grinding, thereby defibrillating the biocellulose, increasing the specific surface area of the cellulose, and exposing more hydroxyl groups, thereby improving the hydrophilicity and biocompatibility of the biocellulose.

[0056] In at least one embodiment, the treatment fluid of the present disclosure can be selected from at least one of an alkaline solution, an inorganic salt solution, and an ionic liquid aqueous solution. In some embodiments of the present disclosure, the base forming the alkaline solution can 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 can 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 can 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.

[0057] As used herein, the "mechanical grinding" includes grinding the dispersion in a horizontal ball mill apparatus after dilution with water to fibrillate the bio-cellulose intertwined with each other in the dispersion to form fibers having a diameter of 15 nm to 35 nm and a length of 1.5 μm to 3.5 μm, wherein the content of the bio-cellulose used for the mechanical grinding ranges between about 0.1 wt% and about 0.5 wt% of the total weight of the dispersion, such as 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%. Thereafter, the swollen and mechanically ground dispersion is purified by a known method including neutralization and desalination, such as dialysis of the dispersion using a semi-permeable membrane to separate salts from the dispersion to obtain the desired fibers.

[0058] In at least one embodiment of the present disclosure, the ground bio-cellulose has a high specific surface area, so that the electrostatic effect, van der Waals force, or hydrogen bonding force between the celluloses is more significant, and the phenomenon of easy aggregation can occur. Therefore, in some embodiments, the present disclosure can further include treating the ground dispersion by ultrasonic oscillation to depolymerize the aggregated bio-cellulose after the mechanical grinding, and then the freeze-drying can be performed as needed.

[0059] In at least one embodiment, the compositions of the present disclosure can comprise beta-1-4-glucan formed fibers and other substances, and the fibers can be presented in the form of lyophilized tablets or dry powder and form a composition with the other substances. In some embodiments, the compositions of the present disclosure can also include at least one of the group consisting of organic nutrients, probiotics, drugs, dietary fibers, flavorings, dispersants, wetting agents, lubricants, thickeners, stabilizers, preservatives, antioxidants, antibacterial agents, and coloring agents, and the fibers of the present disclosure do not negatively affect each of the above ingredients. In some embodiments, the fibers of the present disclosure can have a synergistic effect with the above ingredients.

[0060] In at least one embodiment, the organic matter nutrient of the present disclosure includes an extract, such as from a culture broth of the microorganism described above that is statically cultured. In some embodiments of the present disclosure, the flavoring agent includes a sweetener and / or a flavor. In some embodiments of the present disclosure, the probiotic includes a bacterium such as Enterococcus, Lactobacillus, Bacillus, Clostridium, Lactococcus lactis, Leuconostoc, Pediococcus, Carnobacterium, Vagococcus, Tetragenococcus, Bifidobacterium, Atopobium, Weissella, Abiotrophia, Granulicatella, Oenococcus, Paralactobacillus, and any combination thereof, and Saccharomyces boulardii. In some embodiments of the present disclosure, the probiotic can be selected from the group consisting of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus rhamnosus, Bifidobacterium longum, and any combination thereof.

[0061] In at least one embodiment, the drug of the present disclosure can be a Western medicine or a traditional Chinese medicine, for example, a traditional Chinese medicine or a Western medicine used clinically for gastrointestinal diseases, or a traditional Chinese medicine or a Western medicine with potential as a drug for treating gastrointestinal diseases. For example, the traditional Chinese medicine can be kudzu root, hemp, scutellaria, coptis root, phellodendron, atractylodes, patchouli, amomum villosum, tuckahoe, umbellate, coix seed, cinnamon bark, dried ginger, evodia rutaecarpa, pepper, atractylodes macrocephala, yam, lentil, psoralea corylifolia, alpinia oxyphylla, white peony root, schisandra chinensis, black plum, gallnut, terminalia chebula, nutmeg, lotus seed, gorgon fruit, rosa laevigata fruit, papaya, Huoxiang Zhengqi powder, kudzu root, coptis root, scutellaria baicalensis decoction, Baohe pills, shenlingbaizhu powder, Tongxie Yaofang, Sishen pills, and any combination thereof.

[0062] In some embodiments of the present disclosure, fibers formed from β-1-4-glucan or compositions comprising the formed fibers can be administered when symptoms are expected to occur or before symptoms occur to achieve a preventive and protective effect. For example, the compositions of the present disclosure can be administered to individuals in need of treatment or prevention of diarrhea, constipation, or irritable bowel syndrome at a dose of 1 to 3 times a day, and each dose of the lyophilized tablet contains 0.02 grams to 0.12 grams of fiber. In some embodiments of the present disclosure, when fibers formed from β-1-4-glucan are administered directly, they are administered to individuals in need of treatment or prevention of diarrhea, constipation, or irritable bowel syndrome 1 to 4 times a day, and each dose contains 0.02 grams to 0.12 grams of fiber.

[0063] In some embodiments of the present disclosure, fibers formed from β-1-4-glucan or compositions comprising the fibers formed from β-1-4-glucan can be administered at or after the onset of symptoms to alleviate the symptoms. In some embodiments of the present disclosure, the administration method can be as described above.

[0064] In at least one specific embodiment of the present disclosure, the fiber formed of β-1-4-glucan or the composition comprising the formed fiber can be orally administered twice a day at intervals of 1 to 12 hours, for example, at intervals of 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours or 12 hours to treat or alleviate the aforementioned symptoms. In some specific embodiments of the present disclosure, the fiber formed of β-1-4-glucan or the composition comprising the formed fiber can be administered before meals, after meals or before bedtime. In one specific embodiment, the fiber formed of β-1-4-glucan or the composition comprising the formed fiber can be orally administered three times a day at intervals of 4 to 8 hours. Optionally, the amount can be administered more than 3 times, for example 4 times, until a more clear symptom relief is obtained.

[0065] The present disclosure will be described in further detail with reference to the following examples, which are however in no way intended to limit the scope of the present disclosure.

[0066] Test subjects

[0067] Subjects aged 21-50 years, regardless of gender, with persistent gastrointestinal discomfort were recruited. Patients diagnosed with irritable bowel syndrome according to the Rome IV criteria were selected as trial subjects.

[0068] The Rome IV criteria classify functional gastrointestinal disorders (FGIDs) based on organ location:

[0069] Esophageal diseases

[0070] A1. Functional chest pain; A2. Functional heartburn; A3. Reflux sensitivity; A4. Throat bulb sensation; A5. Functional dysphagia

[0071] A. Gastroduodenal diseases

[0072] B1. Functional dyspepsia; B1a. Postprandial distress syndrome (PDS); B1b. Epigastric pain syndrome (EPS); B2. Belching; B2a. Excessive belching; B2b. Excessive belching; B3. Nausea and vomiting; B3a. Chronic nausea and vomiting syndrome (CNVS); B3b. Cyclic vomiting syndrome (CVS); B3c. Cannabinoid hyperemesis syndrome (CHS); B4. Rumination syndrome

[0073] B. Intestinal diseases

[0074] C1. Irritable bowel syndrome (IBS); Irritable bowel syndrome with constipation (IBS-C); Irritable bowel syndrome with diarrhea (IBS-D); Mixed irritable bowel syndrome (IBS-M); Irritable bowel syndrome unclassified (IBS-U)

[0075] C2. Functional constipation; C3. Functional diarrhea; C4. Functional abdominal bloating / distension; C5. Unspecified functional bowel disorder; C6. Opioid-induced constipation

[0076] C. Centrally mediated gastrointestinal pain

[0077] D1. Centrally mediated abdominal pain syndrome (CAPS); D2. Narcotic bowel syndrome (NBS) / opioid-induced gastrointestinal hyperalgesia

[0078] D. Gallbladder and sphincter of Oddi diseases

[0079] E1. Biliary pain; E1a. Functional gallbladder disorder; E1b. Functional biliary sphincter of Oddi disorder; E2. Functional pancreatic sphincter of Oddi disorder

[0080] E. Anal diseases

[0081] F1. Fecal incontinence; F2. Functional anorectal pain; F2a. Levator ani syndrome; F2b. Unspecified functional anorectal pain; F2c. Spasmodic anorectal pain; F3. Functional defecation disorder; F3a. Insufficient defecation motility; F3b. Uncoordinated defecation

[0082] Doctors assess whether a patient's gastrointestinal discomfort is irritable bowel syndrome based on whether the symptoms began at least six months ago, and whether there has been recurrent abdominal pain on an average of at least one day a week in the past three months, and whether it is associated with two or more of the following criteria: related to bowel movements, related to changes in the frequency of bowel movements, and related to changes in the form of stool. After excluding other organic diseases (such as excluding other diseases through medical history, medication history, physical examination, stool examination, blood tests, endoscopy, X-ray, etc.), if the conditions are met, the doctor will diagnose the patient with irritable bowel syndrome.

[0083] Irritable bowel syndrome is classified according to the Bristol stool form scale (BSFS) based on the softness and hardness of the stool as follows:

[0084] IBS-constipation (IBS-C): ≥25% of stools are hard and <25% are soft;

[0085] IBS-D: ≥25% of stools are soft and <25% are hard;

[0086] IBS-Mixed (IBS-M): ≥25% of stools are soft and ≥25% are hard; and

[0087] Irritable bowel syndrome unclassified (IBS-U): cannot be classified into the above three types.

[0088] Among the patients, only those with irritable bowel syndrome were given priority to avoid other factors affecting the observation.

[0089] Example 1

[0090] Test methods

[0091] The patient orally took one 10 ml portion of the composition containing 0.2 wt% of fiber formed of β-1-4-glucan and the balance being water before lunch and dinner every day.

[0092] Patients answered the following question using a 7-point balanced scale after the end of the test: "How do you evaluate the degree of relief of your IBS symptoms compared to before entering the test? For example, the degree of relief of diarrhea, abdominal pain, bloating, persistent urge to defecate and frequency of defecation, proportion of soft stool, consistency of stool, incomplete defecation, and other IBS symptoms?" to evaluate the effect of the fiber formed of β-1-4-glucan on the relief of symptoms according to the patient's answer.

[0093] 7-point balanced scale:

[0094] • significant relief

[0095] • moderate relief

[0096] • slight relief

[0097] • no change

[0098] • slightly severe

[0099] • moderate severity

[0100] • significant severity

[0101] Among them, those who answered significant relief, moderate relief, and slight relief are listed as effective.

[0102] Case 1

[0103] A 47-year-old male patient with diarrhea-predominant irritable bowel syndrome had three to four episodes of diarrhea per day. The patient underwent a 3-day test, and after the end of the test, answered the above question using a 7-point balanced scale, showing significant relief, and reported that diarrhea did not occur during the test period, and the day after the end of the test, and the effect was excellent.

[0104] Case 2

[0105] A 26-year-old female patient with constipation-predominant irritable bowel syndrome took a soft stool agent prescribed by a doctor, but still had about 3 to 5 days of defecation once a day. The patient underwent a 7-day test, and after the end of the test, answered the above question using a 7-point balanced scale, and the result showed significant relief of symptoms, and the patient responded that she could defecate once a day in the morning and evening during the test period, and the day after the test, she could also maintain smooth defecation.

[0106] Example 2

[0107] Test method

[0108] At the onset of symptoms or before the anticipated onset of symptoms, patients orally administered a 10 ml portion of a composition containing 0.2% by weight of fiber composed of β-1-4-glucan, with the balance being water. After the study, patients responded to the same 7-point balanced scale as in Example 1 to assess the symptom-alleviating effect of the fiber composed of β-1-4-glucan.

[0109] Case 3

[0110] A 34-year-old woman with unclassified irritable bowel syndrome (IBS) often experienced stress-induced abdominal pain. She took the composition orally when her abdominal pain began and answered the questions at least one hour later. The results showed significant relief of her abdominal pain, with the patient responding that it subsided within 5 to 10 minutes.

[0111] Case 4

[0112] A 36-year-old woman with unclassified irritable bowel syndrome (IBS) often experienced stress-related abdominal pain. She took the composition orally when her abdominal pain began and answered the questions at least one hour later. The results also showed significant relief of her abdominal pain, with the patient responding that it subsided within 5 to 10 minutes.

[0113] Case 5

[0114] A 36-year-old male suffered from unclassified irritable bowel syndrome (IBS) for six years, particularly diarrhea the next day after drinking beer. The patient took the above-mentioned composition orally 15 to 20 minutes before each drink, and then drank alcohol. The patient answered the above questions at least one day after drinking, and the results showed significant relief, meaning no diarrhea. The patient continued the trial, drinking alcohol at least five times, at least three to six days apart, and reported significant relief of diarrhea, with no diarrhea the next day after drinking.

[0115] Example 3

[0116] A 50-year-old male with diarrhea-predominant irritable bowel syndrome experienced daily diarrhea, particularly worsening symptoms during periods of stress. He underwent a three-day trial, taking two servings of the aforementioned composition orally, one at the onset of symptoms and one at bedtime. Following the trial, he responded to a 7-point balanced scale, revealing significant symptom relief and no diarrhea for four days. He subsequently reported a recurrence of diarrhea on the fifth day after the trial, but continued taking two servings of the composition daily, as described above, without further diarrhea.

Claims

1. Use of a fiber formed from β-1-4-glucan in preparing a composition for treating or preventing irritable bowel syndrome, wherein: The fibers have a diameter of 15 to 35 nanometers and a length of 1.5 to 3.5 micrometers, The fibers are obtained from biocellulose, The biocellulose is fermented by at least one bacteria selected from the group consisting of Gluconacetobacter, Acetobacter, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Enterobacter, Azotobacter and Agrobacterium. The irritable bowel syndrome is constipation-type irritable bowel syndrome, diarrhea-type irritable bowel syndrome, mixed irritable bowel syndrome or unclassified irritable bowel syndrome.

2. The use according to claim 1, characterized in that The fiber has an aspect ratio of 60 to 150.

3. The use according to claim 1, characterized in that The composition is administered to an individual in need of treating or preventing irritable bowel syndrome at a dose of 1 to 4 times a day, and each dose of the composition contains 0.02 to 0.12 grams of the fiber.

4. The use according to claim 3, characterized in that The composition is administered to the subject in the form of a lyophilized tablet.

5. The use according to claim 1, characterized in that The composition is administered to an individual in the form of fibers formed from the β-1-4-glucan and a liquid medium.

6. The use according to claim 5, characterized in that The liquid medium is water.

7. The use according to claim 5, characterized in that The fiber is present in an amount of 0.2 wt% to 1.2 wt% based on the total weight of the composition.

8. The use according to claim 7, characterized in that The composition includes 0.1 ml of water, and OD 620 It is greater than 0.25 to 1.

25.

9. The use according to claim 8, characterized in that The OD 620 0.4 to 1.

22.

10. The use according to claim 1, characterized in that The bacteria is at least one selected from the group consisting of Acetobacter xylinis, Gluconacetobacter hansenii, Gluconacetobacter xylinis and Gluconacetobacter saccharinii.

11. The use according to claim 1, characterized in that The composition further comprises at least one of the group consisting of organic nutrients, probiotics, medicines, flavoring agents, dispersants, wetting agents, lubricants, thickeners, stabilizers, preservatives, antioxidants, antibacterial agents and colorants.

12. The use according to claim 1, characterized in that The composition is administered orally to a subject in need thereof.