Nutritional compositions for improving tumor-related diarrhea

Abstract

This invention belongs to the field of nutritional compositions and provides a nutritional composition for improving tumor-associated diarrhea. The composition comprises two essential components: i) one or more low-methoxyl pectin sources, and ii) one or more galactomannan sources; wherein the mass ratio of the low-methoxyl pectin to the galactomannan in the composition is (1-7):1. The composition of this invention is simple in composition, economical, and has an ameliorative / alleviating effect on tumor-associated diarrhea.

Description

Technical Field

[0001] This invention belongs to the field of nutritional compositions, and relates to a nutritional composition that improves / alleviates tumor-related diarrhea, its preparation method, and its application. Background Technology

[0002] Diarrhea is characterized by a significant increase in the frequency of bowel movements, loose stools, decreased stool consistency (water content >80%), daily stool volume exceeding 200g, or stools containing mucus, blood, pus, or undigested food. It is often accompanied by symptoms such as urgency, anal discomfort, and incontinence. Diarrhea in cancer (DIC) is a serious and potentially fatal complication of cancer treatment, significantly impacting patients' quality of life. Its pathogenesis is currently unclear. Literature reports an incidence of approximately 12.77% for DIC. Diarrhea can be caused by the tumor itself or by various treatments, including:

[0003] 1) Chemotherapy-induced diarrhea (CID): Chemotherapy-induced diarrhea accounts for 40.83% of all cancer-related diarrhea cases, making it the most common cause of diarrhea in cancer patients. Chemotherapy drugs often have strong cytotoxicity and can directly damage intestinal cells. Current chemotherapy regimens often use high-dose combination therapy, leading to increased intestinal damage and diarrhea. Common drugs that can cause chemotherapy-induced diarrhea clinically include methotrexate, doxorubicin, topotecan, and gefitinib, with 5-fluorouracil (5-FU), irinotecan (CPT-11), and their combination chemotherapy regimens being the most common causes, with an incidence rate as high as 50%-80%.

[0004] 2) Radiation therapy-induced diarrhea (RTID): The overall incidence of diarrhea caused by radiation therapy is approximately 35%. Intestinal secretion is mainly accomplished by mucosal crypt cells. Radiation therapy can directly cause damage to the intestinal mucosa, the severity of which depends on factors such as the direct irradiation site, irradiation range, and irradiation dose. When higher doses of irradiation are used, the number of crypt cells decreases, leading to radiation proctitis, which causes acute exudative diarrhea or delayed proctitis, affecting intestinal muscle contraction and motility.

[0005] 3) Targeted therapy-related diarrhea: Studies have shown that diarrhea is a common adverse reaction to many targeted therapies. Compared to patients receiving standard treatment regimens, cancer patients using erlotinib, gefitinib, lapatinib, sorafenib, and sunitinib have a significantly increased risk of diarrhea of ​​all grades. Regarding mTOR inhibitors, diarrhea is associated with gut microbiota imbalance and malabsorption.

[0006] 4) Immunotherapy-related diarrhea: A specific adverse immune reaction caused by immune checkpoint inhibitors, which is similar to autoimmune diseases in many ways, and diarrhea is one of the most common adverse reactions, especially after treatment with anti-cytotoxic T-lymphocyte-associated antigen 4.

[0007] 5) Diarrhea following tumor surgery: Surgery for certain types of tumors, especially those involving changes in the anatomy and physiological function of the digestive tract, often leads to frequent diarrhea in cancer patients. For example, excessively wide anastomoses after gastric cancer surgery, rapid food entry into the intestines and reduced water reabsorption after intestinal resection, and decreased digestive enzymes after surgery for gastric, gallbladder, and pancreatic tumors.

[0008] 6) Tumor-related factors: Endocrine tumors such as vasoactive intestinal peptide tumors, gastrinomas, apo-peptide hormone-producing tumors (APUD tumors), and carcinoid syndromes can produce one or more bioactive substances, causing water and electrolyte imbalances that directly lead to diarrhea. Pancreatic tumor patients may also experience diarrhea due to poor bile salt absorption. In addition, if patients have intestinal obstruction, anemia, cachexia, etc., it will also affect digestive and absorptive functions, thus leading to diarrhea.

[0009] Currently, oral rehydration salts, montmorillonite, loperamide, and other antidiarrheal drugs are commonly used in clinical practice to treat tumor-related diarrhea. Complex cases of diarrhea (diarrhea accompanied by fever, vomiting, intestinal colic, bloody stools, or more than 10 bowel movements per day) are treated with intravenous rehydration, subcutaneous octreotide injections, antibiotics, and oral hormone therapy.

[0010] However, the aforementioned medications have varying degrees of indications, contraindications, and side effects: Montmorillonite, a natural clay composed of aluminum hydroxide-magnesium carbonate disilicate, cannot be taken long-term, as it can easily lead to constipation and hard stools; the maximum daily dose of loperamide, commonly used clinically, should not exceed 16 mg. It has some side effects in treating acute and chronic diarrhea, such as allergic rashes, urticaria, and itching, as well as gastrointestinal symptoms (such as dry mouth, abdominal distension, loss of appetite, gastrointestinal spasms, nausea, and vomiting) and central nervous system symptoms (such as dizziness, headache, and fatigue). Side effects may include rare allergic reactions, anaphylactic shock, and urinary retention, with significant side effects. Budenede is used to treat chemotherapy-related diarrhea that is difficult to control with loperamide. Common adverse reactions include respiratory symptoms (such as hoarseness, cough, and throat irritation), oropharyngeal symptoms (such as oropharyngeal candidiasis), and gastrointestinal symptoms (such as dysphagia). Other adverse reactions include skin symptoms (such as urticaria, dermatitis, pruritus, erythema, and angioedema) and mental symptoms (such as depression, anxiety, irritability, restlessness, and hyperactivity in children).

[0011] In most cases, the aforementioned treatments are not suitable for cancer patients with specific physical conditions. Frequent and severe diarrhea necessitates reducing chemotherapy dosages or even discontinuing treatment, and severe diarrhea is a significant factor contributing to increased mortality. Therefore, the development of products suitable for cancer patients that can alleviate or improve diarrhea is urgently needed.

[0012] Reference 1 discloses a traditional Chinese medicine composition for treating cancer-related diarrhea, with Psoralea corylifolia as the principal ingredient, Schisandra chinensis and Prunus mume as assistant ingredients, Euryale ferox, Nelumbo nucifera, Punica granatum peel and Angelica dahurica as adjuvant ingredients, and Zingiber officinale (processed) as the guiding ingredient. This composition uses traditional Chinese medicine ingredients, which are expensive and will increase the financial burden on cancer patients. Furthermore, Psoralea corylifolia has certain toxicity; long-term use by cancer patients can lead to liver and kidney damage, and to some extent, weight loss. In addition, Zingiber officinale (processed) irritates the gastrointestinal mucosa, causing gastrointestinal reactions, resulting in poor patient compliance and difficulty in long-term adherence.

[0013] Reference 2 discloses a traditional Chinese medicine composition for treating diarrhea caused by pyrotinib, comprising the following components by weight: Codonopsis pilosula 10g, Poria cocos 10g, stir-fried Atractylodes macrocephala 10g, prepared Glycyrrhiza uralensis 6g, Amomum villosum 6g, salt-processed Psoralea corylifolia 10g, charred Massa fermentata 10g, Areca catechu 10g, vinegar-processed Cyperus rotundus 10g, charred Hordeum vulgare 10g, Coptis chinensis 3g, Polyporus umbellatus 20g, and Terminalia chebula 10g. This composition is only indicated for patients with HER2-positive advanced breast cancer treated with pyrotinib, thus limiting its applicability to a limited population.

[0014] Reference 3 discloses an extraction method for ginsenosides and their application in preventing and treating diarrhea induced by antitumor drugs. Ginsenoside Rh2 is combined with a tyrosine kinase inhibitor to create an anti-breast cancer drug for preventing and treating diarrhea. The ginsenoside Rh2 in this antidiarrheal product belongs to the protopanaxadiol (PPD) type saponin, with a glucose group at C-3 and no glucose group at C-20. It is a rare component among ginsenosides, belonging to secondary saponins. This means that ginsenoside Rh2 cannot be directly extracted from ginseng; it requires conversion from extracted ginsenosides to prepare ginsenoside Rh2. The high cost of the raw materials and processing increases the economic burden on cancer patients.

[0015] Reference 4 discloses an antidiarrheal composition containing macromolecular gum and polymers, suitable for tumor-related diarrhea, as well as diarrhea caused by antibiotics and drug treatment, diarrhea caused by inflammatory bowel disease, diabetic diarrhea, irritable bowel syndrome, persistent diarrhea, chronic diarrhea, diarrhea caused by viral or bacterial infections, diarrhea due to intolerance to enteral nutrition in critically ill patients, and diarrhea-constipation alternation, exhibiting a bidirectional regulatory effect on diarrhea and constipation. However, this composition has the following drawbacks: 1) This composition is not designed specifically for diarrhea in cancer patients, and the causes of cancer-related diarrhea and the needs of cancer patients have not been thoroughly studied, resulting in poor targeting; 2) The galactooligosaccharides in the composition only have a regulatory effect on some intestinal flora, suitable for patients with mild diarrhea, but difficult to exert a regulatory effect on patients with moderate to severe diarrhea, especially those with severe intestinal flora imbalance; 3) It lacks components that repair the intestinal mucosa and enhance the patient's own resistance, and can only temporarily relieve the symptoms of diarrhea caused by radiotherapy, without fundamentally improving diarrhea, and the effect decreases with long-term use.

[0016] It is evident that some research has been conducted in this field on products for stopping or assisting in stopping diarrhea and relieving diarrhea. However, there is still room for further improvement in targeted research and application for relieving diarrhea of ​​different causes.

[0017] References:

[0018] Reference 1: CN115154576B

[0019] Reference 2: CN114588235B

[0020] Reference 3: CN117025712B

[0021] Reference 4: CN110448569A Summary of the Invention

[0022] The problem the invention aims to solve

[0023] Existing antidiarrheal or antidiarrheal products have the following drawbacks: 1) They have complex ingredients and high costs for raw materials and processing, which increases the economic burden on patients; 2) They are limited in terms of symptoms and applicable populations, and have many contraindications; 3) They are designed for all people who may have diarrhea, without addressing the physiological characteristics and needs of diarrhea caused by different factors; 4) They are usually only suitable for short-term diarrhea relief, and are mostly provided in the form of drugs, making them almost unsuitable for long-term use, and lacking data on long-term efficacy; 5) These products have a high incidence of abdominal bloating, are prone to causing constipation, digestive symptoms and other side effects, and cannot be used for long periods.

[0024] For specific groups, such as cancer patients, diarrhea may occur due to the disease or during treatment. In such cases, the economic burden on these patients must be considered, as this diarrhea may be long-term due to factors such as weakened immunity, disease progression, or treatment duration. Currently, there are no clearly reported solutions for this. Therefore, to overcome the shortcomings of existing technologies, this invention provides a nutritional composition. This composition is designed with components specifically tailored to the etiology and pathological characteristics of diarrhea in cancer patients. It is simple, economical, and suitable for long-term use by cancer patients to improve / alleviate cancer-related diarrhea. This composition regulates the balance of intestinal flora, promotes the repair of intestinal mucosal cells, reduces the duration of diarrhea, aids absorption, has no side effects, and has a significant long-term effect in improving / alleviating recurrent diarrhea.

[0025] Solution for solving the problem

[0026] [1]. This invention provides a nutritional composition comprising the following two essential components:

[0027] i) Low-methoxyl pectin from one or more sources, and

[0028] ii) Galactomannan from one or more sources;

[0029] Furthermore, in the composition, the mass ratio of the low-methoxyl pectin to the galactomannan is (1-7):1.

[0030] [2]. The composition according to [1], wherein the mass ratio of the low methoxyl pectin to the galactomannan is (1-3):1.

[0031] [3]. The composition according to [1] or [2], wherein,

[0032] The low-methoxyl pectin includes one or more of the following: low-methoxyl pectin derived from grapefruit, low-methoxyl pectin derived from lemon, low-methoxyl pectin derived from citrus, and low-methoxyl pectin derived from apple.

[0033] The galactomannan includes one or more of the following: galactomannan derived from guar beans, galactomannan derived from sesame beans, galactomannan derived from kohlrabi beans, galactomannan derived from cassia seeds, and galactomannan derived from locust beans.

[0034] [4]. The composition according to any one of [1]-[3], wherein,

[0035] The degree of esterification of the low-methoxyl pectin is less than 50%;

[0036] The galactomannan is obtained by polymerizing mannose and galactose in a ratio of (1.6 to 2):1 via glycosidic bonds, and has a relative molecular weight range of 1000 to 100000 Da.

[0037] [5]. The composition according to any one of [1]-[4], wherein,

[0038] The galactomannan is obtained by polymerizing mannose and galactose in a 2:1 ratio via glycosidic bonds, wherein 80% of the galactomannan has a relative molecular weight of less than 20,000 Da.

[0039] [6]. The composition according to any one of [1]-[5], wherein,

[0040] The composition may also include fruit and vegetable ingredients, including one or more ingredients derived from shiitake mushrooms, hawthorn, apples, citrus fruits, pumpkins, bananas, lemons, and grapefruits.

[0041] [7]. The present invention also provides a method for preparing the composition according to any one of [1]-[6], wherein the preparation method comprises: weighing the required amount of low methoxy pectin, galactomannan and fruit and vegetable components under an ambient humidity of ≤65%, and mixing them evenly to obtain the composition.

[0042] [8]. Furthermore, the present invention also provides the use of the composition according to any one of [1]-[6] or the composition prepared according to the preparation method described in [7] in the preparation of food for improving / alleviating tumor-related diarrhea.

[0043] [9]. According to the application described in [8], the diarrhea is selected from one or more of the following: tumor chemotherapy-related diarrhea, tumor radiotherapy-related diarrhea, targeted drug-related diarrhea, antibiotic treatment-related diarrhea, immunotherapy-related diarrhea, diarrhea caused by the tumor itself, and diarrhea caused by adverse reactions after tumor surgery.

[0044]

[10] . According to the application described in [8] or [9], wherein the food is a food for special medical purposes.

[0045] The effects of the invention

[0046] By implementing the above technical solution, the present invention can achieve the following technical effects:

[0047] 1. The technical solution of the present invention is a nutritional composition specifically designed for cancer patients, which has better targeting and applicability and can significantly improve diarrhea caused by cancer symptoms or treatment.

[0048] 2. This invention scientifically screens the types and proportions of low-methoxyl pectin, galactomannan, and fruit and vegetable powders in the composition to fully utilize the efficacy and synergistic effects of different components: 1) Increases the viscosity of the nutrient solution and delays gastric emptying; 2) Adsorbs toxic substances produced by tumor metabolism and drug treatment, reducing intestinal irritation; 3) Regulates intestinal flora, proliferates beneficial bacteria, and reduces the production of pathogenic bacteria; 4) Promotes the growth and differentiation of colonic mucosal cells, reduces chronic inflammatory response, and improves intestinal mucosal barrier function and absorption function; 5) Affects the pH and osmotic pressure of the digestive tract, effectively improving the problems of low intestinal flora colonization resistance and intestinal dysfunction in patients with diarrhea.

[0049] 3. The composition of the present invention does not irritate the gastrointestinal tract, is flexible in its use, can be administered via tube feeding or orally, has no side effects, can be taken for a long time, and can also provide certain nutritional supplements, which is beneficial to maintaining the body's immunity.

[0050] 4. The composition of the present invention is simple to prepare, and the product is economical and cost-effective, making it suitable for large-scale industrial production. Attached Figure Description

[0051] Figure 1 Experimental Example 1: Effects of in vitro simulated tube feeding experiment;

[0052] Figure 2 Comparative Example 1: Effects of in vitro simulated tube feeding experiment;

[0053] Figure 3 The amount of butyric acid produced by in vitro fermentation of different experimental samples;

[0054] Figure 4 Fecal condition of mice in each group. Detailed Implementation

[0055] The following describes embodiments of the present invention, but the present invention is not limited thereto. The present invention is not limited to the various configurations described below, and various modifications can be made within the scope of the claims. Embodiments and examples obtained by appropriately combining the technical means disclosed in different embodiments and examples are also included in the technical scope of the present invention.

[0056] In this specification, the range of values ​​referred to as "value A to value B" refers to the range including the endpoint values ​​A and B.

[0057] In this specification, the numerical range indicated by "above" or "below" refers to the numerical range that includes the stated number.

[0058] In this specification, the word "may" has two meanings: to perform a certain process and not to perform a certain process.

[0059] In this specification, the terms "optional" or "optional" are used to indicate the use or omission of certain substances, components, procedures, application conditions, etc.

[0060] Unless otherwise specified, “room temperature” in this instruction manual usually refers to a temperature of 25±2℃.

[0061] All unit names used in this manual are international standard unit names, and unless otherwise stated, the "%" used refers to weight or mass percentage content.

[0062] In this instruction manual, "parts" refers to parts by weight.

[0063] In this specification, references to "some specific / preferred embodiments," "other specific / preferred embodiments," "implementation," etc., refer to specific elements (e.g., features, structures, properties, and / or characteristics) related to that embodiment, which are included in at least one of the embodiments described herein and may or may not be present in other embodiments. Furthermore, it should be understood that these elements may be combined in any suitable manner in various embodiments.

[0064] Unless otherwise defined, other technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0065] This invention primarily provides a composition for nutritional or functional foods, particularly a composition suitable for use in foods for special medical purposes. The invention also provides foods comprising this composition. In this invention, "foods for special medical purposes" refers to specially processed and formulated foods designed to meet the specific nutritional or dietary needs of individuals with restricted food intake, digestive and absorptive disorders, metabolic disorders, or specific disease states. This definition conforms to the provisions of the "General Rules for Foods for Special Medical Purposes" in the National Food Safety Standard.

[0066] Furthermore, the "food" of this invention is not a medicine and cannot replace the therapeutic effect of drugs. The "food" of this invention also does not have the function of preventing or treating diseases. Moreover, this type of food can be consumed alone or in combination with other foods under the guidance of a doctor or clinical nutritionist when necessary. Furthermore, the "diarrhea" of this invention is not considered a disease itself, but rather an accompanying physiological reaction to a non-disease state caused by other diseases or treatment processes.

[0067] The technical solution of this invention is mainly based on the following insights:

[0068] In view of the need to address (prolonged) diarrhea in cancer patients due to disease or treatment, this invention proposes a nutritional composition to improve / alleviate this condition. The composition comprises at least two essential components in combination. The combination of low-methoxyl pectin and galactomannan in this composition has shown significant improvement / alleviation of diarrhea caused by cancer radiotherapy, chemotherapy, and antibiotic treatment. It possesses one or more of the following functions or effects: fermentation by beneficial intestinal bacteria to produce short-chain fatty acids (SCFAs) primarily composed of butyrate, thereby exerting an immunomodulatory effect by inhibiting the activation of transcription factor NF-κB; and by reducing inflammatory factors such as TNF-α, IFN-γ, and IL-1β in plasma and histone deacetylation, affecting the expression of tight junction proteins such as Occludin and Claudin-2, thus restoring the tight junctions of the intestinal barrier and improving intestinal motility in patients with cancer-related diarrhea. This composition significantly improves / alleviates cancer diarrhea caused by different methods (such as cancer radiotherapy, chemotherapy, and antibiotic treatment), and also enhances immunity and reduces the risk of diarrhea.

[0069] This invention investigates the effects of combining low-methoxyl pectin and galactomannan to form a composition through animal experiments. Based on the effects of this composition on diarrhea scores and related indicators in mouse plasma, it was found that the combination can significantly improve / alleviate diarrhea caused by tumor radiotherapy, chemotherapy, and antibiotic treatment.

[0070] The technical solution of the present invention will be further described in detail below:

[0071] <First Aspect>

[0072] A first aspect of the present invention provides a nutritional composition, particularly a nutritional composition for use in foods formulated for special medical purposes. This nutritional composition has the effect of improving / alleviating tumor-related diarrhea. The nutritional composition comprises two essential components: i) one or more sources of low-methoxyl pectin, and ii) one or more sources of galactomannan, wherein the mass ratio of the low-methoxyl pectin to the galactomannan in the composition is (1–7):1.

[0073] (Low methoxyl pectin)

[0074] The low-methoxyl pectin selected in this invention is a water-soluble functional oligosaccharide that cannot be absorbed by the human digestive system. Under acidic conditions in the stomach, low-methoxyl pectin can react with free divalent metal ions (such as Ca2+). 2+The combination of these components forms a spatial network gel structure, which semi-solidifies the nutrients and slows down gastrointestinal emptying. This not only adsorbs toxic substances (such as secondary bile acids, nitrites, cresols, amine compounds, etc.) and pathogenic microorganisms such as Salmonella produced in the intestine, but also promotes the growth and proliferation of beneficial bacteria such as Bifidobacteria, Lactobacillus, and Streptococcus, while inhibiting the growth of harmful bacteria such as Clostridium perfringens, Enterobacteriaceae, and Pseudomonas, thus improving the intestinal flora structure.

[0075] In principle, there are no particular restrictions on the source of the low-methoxyl pectin used in this invention. For example, in some specific embodiments, the low-methoxyl pectin includes one or more of the following: low-methoxyl pectin derived from grapefruit, low-methoxyl pectin derived from lemon, low-methoxyl pectin derived from citrus, and low-methoxyl pectin derived from apple; various commercially available products can also be used.

[0076] In some specific embodiments, the degree of esterification of the low-methoxyl pectin can be less than 50%, preferably 10% to 40%, etc., and in some specific embodiments, the methoxyl content can be less than 7% or less than 5%.

[0077] In addition, it should be emphasized that the above-mentioned low-methoxyl pectin must be added to the composition in a manner permitted by local laws and regulations. Within the permitted scope, it can be added as a single ingredient or other ingredients containing the ingredient can be used to impart the desired low-methoxyl pectin to the composition.

[0078] (Galactomannan)

[0079] The galactomannan selected in this invention is a water-soluble functional oligosaccharide that cannot be absorbed by the human digestive system. After directly entering the intestines, galactomannan is preferentially utilized by beneficial intestinal bacteria (such as lactobacilli and bifidobacteria), becoming a growth factor for these beneficial bacteria and inhibiting the growth and reproduction of harmful bacteria, thus improving the physiological function of intestinal flora structure. Galactomannan can also reversibly exchange with gastrointestinal cations (especially organic cations), thereby affecting intestinal pH, osmotic pressure, and redox potential, reducing watery diarrhea and exerting a unique bidirectional regulatory effect on the intestines. It is used to stop diarrhea when the user has diarrhea and to relieve constipation when the user has constipation, effectively improving / relieving alternating symptoms of diarrhea and constipation. Patients who take the composition of this invention long-term will not experience adverse symptoms such as diarrhea turning into constipation.

[0080] In principle, there are no particular restrictions on the source of the galactomannan used in this invention. For example, in some specific embodiments, the galactomannan includes one or more of the following: galactomannan derived from guar beans, galactomannan derived from sesame beans, galactomannan derived from tung beans, galactomannan derived from cassia seeds, and galactomannan derived from locust beans, with galactomannan derived from guar beans being preferred. Various commercially available products can also be used.

[0081] In some specific embodiments, the galactomannan is obtained by polymerization of mannose and galactose in a ratio of (1.6 to 2):1 via glycosidic bonds, and has a relative molecular weight range of 1000 to 100000 Da.

[0082] In some preferred embodiments, the galactomannan is obtained by polymerization of mannose and galactose in a 2:1 ratio via glycosidic bonds, wherein 80% of the galactomannan has a relative molecular weight of less than 20,000 Da.

[0083] It should be emphasized that the above-mentioned form of addition of galactomannan to the composition must comply with the permission of local laws and regulations. Within the permitted scope, it can be added as a single ingredient, or other additives containing the ingredient can be used to impart the desired galactomannan to the composition.

[0084] (Dosage ratio)

[0085] Furthermore, in order to obtain better effects in improving / alleviating tumor-related diarrhea, in some specific embodiments, the ratio of i) low-methoxyl pectin and ii) galactomannan in the composition of the present invention can be configured as follows:

[0086] The mass ratio of the low-methoxyl pectin to the galactomannan is (1-7):1.

[0087] It should be noted that the specific absolute content of low-methoxyl pectin and galactomannan in the composition should be set in accordance with local laws and regulations, while ensuring the above-mentioned ratio is met.

[0088] Furthermore, in some preferred embodiments of the present invention, the mass ratio of the low-methoxyl pectin to the galactomannan is (1-6):1; more preferably, the mass ratio of the low-methoxyl pectin to the galactomannan is (1-5):1; even more preferably, the mass ratio of the low-methoxyl pectin to the galactomannan is (1-3):1. Other ratios that can be listed include 10:9, 11:9, 10:7, 12:7, 2:1, 14:5, 14:3, etc.

[0089] Furthermore, the above-mentioned composition has been found to significantly improve / alleviate diarrhea caused by tumor radiotherapy, chemotherapy, and antibiotic treatment. Experimental verification shows that the composition of the present invention improves / alleviates the aforementioned diarrhea by reducing the expression levels of inflammatory factors such as TNF-α, IFN-γ, and IL-1β in plasma. The composition of the present invention also improves / alleviates tumor-related diarrhea by reducing diarrhea scores in mice. In particular, the effect of improving / alleviating diarrhea caused by tumor radiotherapy, chemotherapy, and antibiotic treatment is even better when the contents of the two components are used in a ratio of (1–3):1.

[0090] Therefore, the nutritional composition of the present invention includes at least the low-methoxyl pectin and galactomannan described above.

[0091] Furthermore, there are no particular limitations on other components or other nutrients that can be used in the compositions of the present invention. Without impairing the effects of the present invention, other edible ingredients, food additives or solvent components commonly used in the art can be used. Other nutrients include one or more of proteins, fatty acids, vitamins, minerals or fruits and vegetables.

[0092] In a preferred embodiment, the composition of the present invention may further include fruit and vegetable ingredients.

[0093] In principle, there are no particular restrictions on the source of fruits and vegetables used in this invention. For example, in some specific embodiments, the fruits and vegetables include one or more fruit and vegetable components derived from shiitake mushrooms, hawthorn, apples, citrus fruits, pumpkins, bananas, lemons, and grapefruits. In some preferred embodiments, the fruit and vegetable components of this invention may be derived from shiitake mushrooms and hawthorn.

[0094] Among its components, shiitake mushroom contains natural lentinan, the main component of which is mannoside peptide, a specific immune adjuvant for T lymphocytes. It can promote T lymphocyte maturation, enhance NK cell activity, induce macrophage activity, reduce the toxic side effects of chemotherapy, improve weakened immunity in patients, and alleviate complications. Hawthorn contains abundant organic acids such as hawthorn acid, citric acid, malic acid, and tartaric acid, which can enhance pepsin activity, thereby promoting digestive enzyme secretion and aiding digestion. It can also promote fat breakdown and improve diarrhea caused by malabsorption.

[0095] In addition, it should be emphasized that the above-mentioned fruit and vegetable ingredients must be added to the composition in a manner that complies with local laws and regulations. Within the scope of these regulations, they can be added as individual ingredients or other additives containing the ingredient can be used to impart the desired fruit and vegetable ingredients to the composition.

[0096] Furthermore, the presence of the nutritional composition of the present invention is not particularly limited in principle. At room temperature, it can exist in a liquid state, or in a semi-solid or solid state.

[0097] <Second aspect>

[0098] A second aspect of the present invention is to provide a method for preparing the composition described in the first aspect of the present invention, wherein the preparation method comprises: weighing the required amounts of low-methoxyl pectin, galactomannan and fruit and vegetable components under an ambient humidity of ≤65%, and mixing them uniformly to obtain the composition.

[0099] In one specific embodiment of the present invention, in the preparation method of the composition, the mass percentage of the low-methoxyl pectin is 50% to 70%, the mass percentage of the galactomannan is 15% to 45%, and the mass percentage of the fruit and vegetable components is less than 15%.

[0100] <Third aspect>

[0101] A third aspect of the present invention provides the use of the nutritional composition described in the first aspect or the nutritional composition prepared by the preparation method described in the second aspect in the preparation of a food for improving / alleviating tumor-related diarrhea, wherein the food may be a food for special medical purposes. Therefore, the nutritional composition of the present invention does not relate to the treatment of diarrhea as a disease state.

[0102] In one specific embodiment of the present invention, the diarrhea is selected from one or more of the following: tumor chemotherapy-related diarrhea, tumor radiotherapy-related diarrhea, targeted drug-related diarrhea, antibiotic treatment-related diarrhea, immunotherapy-related diarrhea, diarrhea caused by the tumor itself, and diarrhea caused by adverse reactions after tumor surgery.

[0103] In one specific embodiment of the present invention, the tumor is selected from any one or a combination of solid tumors and non-solid tumors.

[0104] In one specific embodiment of the present invention, the solid tumor is selected from any one or a combination of gastric cancer, colon cancer, bladder cancer, kidney cancer, prostate cancer, breast cancer, lung cancer, brain tumor, bone cancer, pancreatic cancer, liver cancer, and bile duct cancer.

[0105] In one specific embodiment of the present invention, the non-solid tumor is selected from any one or a combination of lymphoma, leukemia.

[0106] In one specific embodiment of the present invention, the composition may be used in combination with any one or a combination of probiotics, oral rehydration salts, fiber supplements, and other foods for special medical purposes.

[0107] In one specific embodiment of the present invention, the composition of the present invention can be any dosage form well known in the food industry (including general food and special food, for example, see the provisions of the Chinese Food Safety Law), and can be prepared using conventional formulation techniques in the art. Formulations suitable for the present invention are selected from any one of powders, granules, oral liquids, suspensions, semi-solids, pills, tablets, capsules, and pastes.

[0108] In one specific embodiment of the present invention, the composition or food of the present invention can be provided to cancer patients by oral or tube feeding.

[0109] In one specific embodiment of the present invention, the dosage of the composition or food of the present invention is related to factors such as the patient's age, health status, tumor progression, treatment method, and concurrent medications, and should be used under the guidance of a physician. The recommended adult dosage is 3-4 times / day, and the recommended children's dosage is 1-2 times / day, 5-10g / time. Patients may also take the composition or food of the present invention concurrently with products that may cause diarrhea to achieve a good improvement / relief effect.

[0110] Example

[0111] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0112] The main raw materials used in this experiment are shown in the table below.

[0113]

[0114] Example 1: A nutritional composition for improving / relieving tumor-related diarrhea, consisting of the following raw materials in parts by weight: 70 parts of low-methoxyl pectin (esterification degree 28%), 25 parts of galactomannan (from guar beans), and 5 parts of hawthorn powder; wherein the mass ratio of the three components is 14:5:1.

[0115] Comparative Example 1: A nutritional composition for improving / alleviating tumor-related diarrhea, comprising the following parts by weight of raw materials: 70 parts of high methoxyl pectin (67% esterification), 25 parts of galactomannan (guar bean source), and 5 parts of hawthorn powder; wherein the mass ratio of the three components is 14:5:1.

[0116] Preparation method: Weigh low-methoxyl pectin or high-methoxyl pectin, galactomannan, and hawthorn powder according to the formula. Add the raw materials to a mixer and mix evenly, controlling the humidity not to exceed 65%. Put the mixed material into a packaging machine, package it in aluminum-plastic bags, and seal it to obtain the final product.

[0117] The compositions of Experimental Example 1 and Comparative Example 1 were prepared into suspensions of 5g / 100mL and 10g / 100mL, respectively. The effects of tube feeding and in vitro diarrhea relief were observed through an in vitro tube feeding simulation test (12mm diameter nasogastric tube).

[0118] Figure 1 The results showed that after the composition of Experimental Example 1 entered the simulated intestine, it rapidly increased the viscosity of the simulated intestinal contents, and the flow rate of the contents within the simulated intestine slowed down. The stool flowing out of the simulated intestinal opening was no longer thin and watery, but rather a nearly formed banana-shaped stool. This indicates that the composition of Experimental Example 1 can improve / alleviate diarrhea by increasing the viscosity of the nutrient solution and delaying gastric emptying. Furthermore, the viscous state of the composition helps to adsorb toxic substances produced by tumor metabolism and drug treatment in the intestine, reducing the irritation of the intestine by these toxic substances.

[0119] In addition, both compositions in Experiment 1 could pass through the tube feed pump normally; Figure 2 The results showed that the composition in Comparative Example 1 could not be performed at a concentration of 10 g / 100 mL due to severe tube blockage caused by localized gelation. Considering the safety of clinical tube feeding applications, subsequent experimental cases all used low-methoxyl pectin (esterification degree 28%).

[0120] Example 2: A nutritional composition for improving / alleviating tumor-related diarrhea, consisting of the following raw materials in parts by weight: 50 parts of low-methoxyl pectin (esterification degree 28%), 45 parts of galactomannan (from guar beans), and 5 parts of shiitake mushroom powder; wherein the mass ratio of the three components is 10:9:1.

[0121] Example 3: A nutritional composition for improving / alleviating tumor-related diarrhea, consisting of the following raw materials in parts by weight: 50 parts of low-methoxyl pectin (esterification degree 28%), 45 parts of galactomannan (derived from sesame beans), and 5 parts of shiitake mushroom powder; wherein the mass ratio of the three components is 10:9:1.

[0122] Example 4: A nutritional composition for improving / alleviating tumor-related diarrhea, consisting of the following raw materials in parts by weight: 50 parts of low-methoxyl pectin (esterification degree 28%), 45 parts of galactomannan (derived from cassia seed), and 5 parts of shiitake mushroom powder; wherein the mass ratio of the three components is 10:9:1.

[0123] Example 5: A nutritional composition for improving / alleviating tumor-related diarrhea, consisting of the following raw materials in parts by weight: 50 parts of low-methoxyl pectin (esterification degree 28%), 45 parts of galactomannan (from locust bean), and 5 parts of shiitake mushroom powder; wherein the mass ratio of the three components is 10:9:1.

[0124] Preparation method: Weigh low-methoxyl pectin, galactomannan and shiitake mushroom powder according to the formula, add the raw materials to the mixer and mix evenly, controlling the humidity not to exceed 65%; put the mixed material into the packaging machine, package and seal it in aluminum-plastic bags to obtain the final product.

[0125] Fresh feces were collected from 5 healthy adults (who had not had enteritis or other digestive tract diseases in the past 3 months and had not taken or injected antibiotics or other drugs). Within 1 hour, the feces were collected, mixed, diluted, and filtered to prepare an intestinal bacterial suspension. The composition of Experiments 2-5 was added to the basal culture medium at a ratio of 8 g / L. Each culture medium was divided into three replicates. After mixing, the mixture was fermented in vitro under anaerobic conditions at 37°C for 24 hours. The supernatant was extracted and the butyric acid content was determined.

[0126] Due to the presence of excessive sulfate-reducing bacteria in the colon, most patients with tumor-associated diarrhea (TAD) exhibit gut microbiota imbalance and butyrate deficiency, which endangers the important acetyl-CoA metabolic pathway, induces changes in cell membrane structure and mucus, and thus facilitates the triggering and persistence of inflammatory processes. Insufficient butyrate in the intestine is one of the reasons for impaired tight junctions of intestinal epithelial cells, altered intestinal mucosal barrier permeability, and intestinal motility disorders in cancer patients. The low-methoxyl pectin and galactomannan in the composition of this invention are both functional oligosaccharides that cannot be digested by the human body. They can directly reach the intestine and be fermented by beneficial bacteria to produce short-chain fatty acids (SCFAs) mainly composed of butyrate. These SCFAs then exert immunomodulatory effects by inhibiting the activation of the transcription factor NF-κB. Furthermore, the generated SCFAs can restore the tight junctions of the intestinal barrier by inhibiting TNF-α, IL-3, and histone deacetylation, affecting the expression of tight junction proteins such as Occludin and Claudin-2, thereby improving intestinal motility and alleviating diarrhea symptoms in patients with TAD.

[0127] Figure 3 In vitro fermentation experiments showed that, under the same experimental conditions, compared with the compositions of Experiments 3-5, the composition of Experiment 2 could ferment probiotics to produce more butyric acid, which helped to repair intestinal epithelial mucosal cells more quickly, restore the tight junction of the intestinal barrier, and improve diarrhea. Therefore, galactomannan from guar bean is preferred in subsequent experimental examples.

[0128] Example 6: A nutritional composition for improving / alleviating tumor-related diarrhea, consisting of the following raw materials in parts by weight: 70 parts of low-methoxyl pectin (esterification degree 28%), 15 parts of galactomannan (from guar beans), and 15 parts of shiitake mushroom powder; wherein the mass ratio of the three components is 14:3:3.

[0129] Example 7: A nutritional composition for improving / alleviating tumor-related diarrhea, consisting of the following raw materials in parts by weight: 60 parts of low-methoxyl pectin (esterification degree 28%), 30 parts of galactomannan (from guar beans), and 10 parts of shiitake mushroom powder; wherein the mass ratio of the three components is 6:3:1.

[0130] Example 8: A nutritional composition for improving / relieving tumor-associated diarrhea, comprising the following parts by weight of raw materials: 50 parts of low-methoxyl pectin (esterification degree 28%), 35 parts of galactomannan (from guar beans), and 15 parts of hawthorn powder; wherein the mass ratio of the three components is 10:7:3.

[0131] Example 9: A nutritional composition for improving / alleviating tumor-associated diarrhea, comprising the following parts by weight of raw materials: 55 parts of low-methoxyl pectin (esterification degree 28%) and 45 parts of galactomannan (from guar beans); wherein the mass ratio of the two components is 11:9.

[0132] Example 10: A nutritional composition for improving / alleviating tumor-related diarrhea, consisting of the following raw materials in parts by weight: 60 parts of low-methoxyl pectin (esterification degree 28%), 35 parts of galactomannan (from guar beans), and 5 parts of hawthorn powder; wherein the mass ratio of the three components is 12:7:1.

[0133] Preparation method: Weigh low-methoxyl pectin, galactomannan, and fruit and vegetable powder (shiitake mushroom powder, hawthorn powder, or others) according to the formula. Add the raw materials to a mixer and mix evenly, controlling the humidity not to exceed 65%. Put the mixed material into a packaging machine, package it in aluminum-plastic bags, and seal it to obtain the final product.

[0134] By comparing composition 6-10 with each indicator specified in GB 29922-2013 "National Food Safety Standard for Foods for Special Medical Purposes", it was found that experimental example 6-10 met the requirements for non-complete nutritional formula foods for special medical purposes.

[0135] Animal Experiment 1 (conducted using the composition of Example 9)

[0136] Experimental objective: To verify the effect of the composition of the present invention on improving / alleviating diarrhea caused by radiotherapy, chemotherapy and antibiotic treatment of tumors.

[0137] Experimental animals: BALA / c mice, weighing 18-22g, 5-6 weeks old, half male and half female, acclimatized for 1 week. CT-26 colon cancer cells derived from BALA / c mice were obtained from the Institute of Clinical Medicine, China-Japan Friendship Hospital.

[0138] Tumor-bearing mouse model: CT-26 cells were resuscitated and inoculated into the back of mice. Animals with well-grown tumors and no surface ulceration were selected and sacrificed. Tumor tissue was dissected, ground under aseptic conditions, and diluted with physiological saline to a tumor cell suspension of 1:3 to 1:4. After microscopic examination showing cell viability ≥95% by 0.4% trypan blue staining, the cells were inoculated into the neck and back of mice (5 × 10⁶ cells per 10⁻ ... 6 (Number of cells / mouse). Surviving and normally growing tumor-bearing mice were randomly divided into four groups: radiotherapy followed by the treatment with the given composition (F1) and prior to the treatment with the given composition (F2); irinotecan treatment followed by the treatment with the given composition (H1) and prior to the treatment with the given composition (H2); antibiotic treatment followed by the treatment with the given composition (K1) and prior to the treatment with the given composition (K2); and a model group (M1). F1, H1, and K1 each had 15 mice, while F2, H2, K2, and M1 each had 10 mice. Ten healthy mice before inoculation served as blank controls (G1).

[0139] Administration method and observation indicators: Groups F1 and F2 received a single high-dose irradiation using a 6MV X-ray linear accelerator, with the irradiation area extending from the pubic symphysis to the anus. The irradiation dose was 20 Gy, and the animals were fed normally after irradiation. Groups H1 and H2 received intraperitoneal injections of irinotecan 75 mg / kg / day, or 1.5 mg / animal / day. Gentamicin (GEN, 2 mL, 80,000 U / vial) and cephalexin capsules (CEF) were prepared as an antibiotic mixture with a mass concentration of 312.5 g / L using sterile saline. Groups K1 and K2 received 0.2 mL / animal by gavage, or 62.5 mg / animal / day.

[0140] The composition of Experimental Example 9 was prepared into a suspension of 0.13 g / mL and administered according to the adult clinical equivalent dose (converted by body surface area method, with a conversion factor of 9.1 between humans and mice). Except for groups G1 and M1, each group was given 0.2 mL / time, three times a day, for 7 consecutive days by gavage. Groups G1 and M1 were given an equal volume of physiological saline by gavage. On day 5, 5 mice from each of groups F1, H1, and K1 were sacrificed for blood collection, and the remaining 10 mice were used for the intervention experiment. The specific experimental design is shown in Table 1.

[0141] Table 1. Mouse grouping and gavage administration

[0142]

[0143] During the period, the general condition of the mice (mental state, fur color, anal color, etc.) was observed daily, and filter paper was placed in the test cage to observe the stool. Scoring was performed according to Akinobu Kurita's method (see Table 2).

[0144] Table 2. Scoring criteria for diarrhea in mice

[0145]

[0146] The test results are from Figure 4 It can be known that:

[0147] On the second day, the F1 group began to show varying degrees of reduced food and water intake, sluggish response, dirty fur, curling up and less movement, and increased bowel movements; on the third day, loose stools and mucus appeared; on the fifth day, all of them reached moderate to severe diarrhea, with tarry stools appearing.

[0148] Group H1 began to experience decreased activity and perianal skin redness and swelling 12 hours after intraperitoneal injection of irinotecan; decreased food intake and weight loss began 24 hours later; all patients developed moderate to severe diarrhea on day 4, with loose stools and some watery stools; and some patients developed bloody stools on day 5.

[0149] On day 2, mice in group K1 developed diarrhea symptoms, including lethargy, reduced food intake, dull fur, yellow loose stools, and secretions. By day 5, all mice had moderate to severe diarrhea, with some exhibiting watery or bloody stools.

[0150] Group M1 was in good general condition, with normal eating and drinking. As the tumor on their back grew, their movement became slower, and on the 4th day, they experienced slightly loose stools and weight loss. In contrast, Group F2, Group H2, and Group K2 only experienced slightly loose stools on the 8th day, and their diarrhea symptoms were significantly reduced compared to Group M1. This indicates that the composition can improve / alleviate diarrhea caused by the tumor itself.

[0151] Seven days after administration (day 12), compared with day 5, the stool scores of groups F1, H1, and K1 were significantly reduced, the condition of each mouse was significantly improved, there was no severe diarrhea, the frequency of defecation was significantly reduced, and the degree of perianal redness and swelling was significantly reduced; indicating that the composition can significantly improve / alleviate diarrhea caused by tumor radiotherapy, chemotherapy, and antibiotic treatment.

[0152] Table 3. Changes in diarrhea scores in mice in the post-treatment composition group

[0153] Grouping Day 5 Day 12 M1 1.3±0.42 1.5±0.5 F1 3.7±0.42 1.9±0.54 H1 3.8±0.32 2.0±0.60 K1 3.6±0.48 1.8±0.64

[0154] Table 4. Diarrhea scores of mice in the group given the composition later and the group given the composition first on day 12.

[0155] Grouping Radiation therapy (Group F) Chemotherapy (Group H) Antibiotic treatment (Group K) Post-supply composition group 1.9±0.54 2.0±0.60 1.8±0.64 First, supply the composition group. 1.8±0.64 1.7±0.56 1.6±0.48

[0156] The results in Tables 3 and 4 show that on day 12, the diarrhea scores of mice in the group given the composition first were lower than those in the group given the composition later. Compared with the diarrhea scores of the group given the composition later on day 5, the scores were significantly lower. This indicates that the composition has an ameliorative / alleviating effect on tumor diarrhea caused by different mechanisms, and can also improve the body's immunity and reduce the risk of diarrhea.

[0157] The expression levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-1β (IL-1β) in plasma were measured using enzyme-linked immunosorbent assay (ELISA). Pro-inflammatory factors such as TNF-α can impair intestinal barrier function, and damage to the intestinal mucosa can lead to diarrhea. Alvarenga et al. found that irinotecan significantly increased the expression levels of TNF-α and IL-1β in the jejunum of mice (Alvarenga EM, Souza LK, Araujo TS, et al. Carvacrol reduces irinotecan-induced intestinal mucositis through inhibition of inflammation and oxidative damage via TRPA1 receptor activation[J]. Chem Biol Interact, 2016, 260:129-140.).

[0158] Table 5. Expression of pro-inflammatory cytokines in plasma of mice in each group

[0159]

[0160] Table 5 shows that on day 5 (D5), the expression levels of TNF-α, IFN-γ, and IL-1β in the plasma of mice in groups F1, H1, and K1 were significantly higher than those in the control group, indicating that experimental doses of radiotherapy, chemotherapy, and antibiotic treatment lead to increased expression of inflammatory factors in plasma. On day 12 (D12), the expression levels of TNF-α and IFN-γ in the plasma of mice in the groups subsequently given the composition (F1, H1, and K1) and the groups initially given the composition (F2, H2, and K2) were significantly lower than those in the groups subsequently given the composition on day 5 (F1, H1, and K1), and the expression level of IL-1β was also reduced to varying degrees. This indicates that the composition can improve intestinal mucosal damage and thus alleviate diarrhea symptoms by reducing the expression levels of TNF-α, IFN-γ, and IL-1β.

[0161] Animal experiment 2 (conducted using the compositions of Experimental Examples 6, 7, and 8 respectively)

[0162] Replace Experiment 9 in Animal Experiment 1 with Experiment 6, 7, and 8 respectively, and conduct the same experiments and tests as in Animal Experiment 1.

[0163] Through testing, it was observed that the application of these experimental examples could still achieve the same level of effect as animal experiment 1. However, the test data from the animal experiment using experimental example 6 showed that when the ratio of low methoxyl pectin to galactomannan was too high (around 5:1), there was also a weakening of local inflammatory factor inhibition.

[0164] Therefore, based on the above animal experiments 1 and 2, it can be concluded that when the ratio of low-methoxyl pectin to galactomannan is controlled in a reasonable manner, it can significantly alleviate diarrhea.

[0165] Application Example 1:

[0166] A 67-year-old male patient with gastric cancer who underwent partial gastrectomy had a history of chronic diarrhea for over 5 years. For many years, he had tried treating diarrhea with loperamide, diphenoxylate, codeine, or opium tincture. The sample was prepared according to Experiment 8, and administered 15g twice daily, during which time he discontinued other antidiarrheal medications. After 5 days of continuous use, his stools became mostly formed, and his diarrhea symptoms significantly improved. After 14 days of continuous use, the diarrhea symptoms disappeared. He continued use for 60 days without any adverse reactions. He continued use for over a year, combining it with other medications, without experiencing diarrhea or other adverse symptoms. The patient reported that the composition tasted good, and during this period, his appetite improved, his willingness to eat increased, and he gained weight.

[0167] Application Example 2:

[0168] A 54-year-old male patient underwent radical resection and radiotherapy for colorectal cancer. Postoperatively, he developed watery diarrhea, which was unresponsive to probiotics and OTC antidiarrheal medications. The sample was prepared according to the method used in Case 8, and the patient was given 15g twice daily, after discontinuing other antidiarrheal medications. After 3 days of treatment, the frequency of diarrhea decreased. After 7 days of continuous treatment, stools became more formed and diarrhea symptoms significantly improved. After 20 days of continuous treatment, diarrhea symptoms disappeared, and weight loss slowed. He continued treatment for over six months without any adverse reactions or diarrhea recurrences, and his weight increased during the treatment period.

[0169] In summary, this invention, through screening methoxylated pectin with different degrees of esterification, galactomannan with different molecular weights and structures, and fruit and vegetable powders from different sources, and their corresponding addition amounts, scientifically proportions the ingredients to fully leverage their efficacy and synergistic effects. The resulting composition achieves the following effects: 1) increasing the viscosity of the nutrient solution and delaying gastric emptying; 2) reducing intestinal irritation by adsorbing toxic substances produced by tumor metabolism and drug treatment; 3) regulating intestinal flora, proliferating beneficial bacteria, promoting butyrate production in the intestine, promoting the growth and differentiation of colonic mucosal cells, reducing chronic inflammatory responses, and improving intestinal mucosal barrier function and absorption function; 4) affecting the pH and osmotic pressure of the digestive tract, effectively improving the problems of low intestinal flora colonization resistance and intestinal dysfunction in patients with diarrhea; 5) animal experiments show that the composition has a good improvement / relief effect on tumor-related diarrhea; 6) application examples show that the composition can quickly stop diarrhea, has the advantages of good taste and no toxic side effects, and long-term use can significantly improve / relieve diarrhea and reduce the incidence of diarrhea during continuous tumor treatment.

[0170] Industrial availability

[0171] The nutritional composition provided by this invention for improving / alleviating tumor-related diarrhea can be prepared industrially.

Claims

1. A nutritional composition for improving / alleviating tumor-related diarrhea, characterized in that, The composition comprises the following two essential components: i) Low-methoxyl pectin from one or more sources, and ii) Galactomannan derived from guar beans; Furthermore, in the composition, the mass ratio of the low-methoxyl pectin to the galactomannan is (1~3):1; The low-methoxyl pectin includes one or more of the following: low-methoxyl pectin derived from grapefruit, low-methoxyl pectin derived from lemon, low-methoxyl pectin derived from citrus, and low-methoxyl pectin derived from apple; the degree of esterification of the low-methoxyl pectin is 10-50%, and the methoxyl content of the low-methoxyl pectin is less than 7%. The galactomannan is obtained by polymerization of mannose and galactose in a 2:1 ratio via glycosidic bonds, and has a relative molecular weight range of 1000~100000 Da.

2. The nutritional composition according to claim 1, characterized in that, The degree of esterification of the low-methoxyl pectin is 10-40%.

3. The nutritional composition according to claim 1 or 2, characterized in that, 80% of the galactomannan has a relative molecular weight of less than 20,000 Da.

4. The nutritional composition according to claim 1, characterized in that, The diarrhea is selected from one or more of the following: tumor chemotherapy-related diarrhea, tumor radiotherapy-related diarrhea, targeted drug-related diarrhea, antibiotic treatment-related diarrhea, immunotherapy-related diarrhea, diarrhea caused by the tumor itself, and diarrhea caused by adverse reactions after tumor surgery.

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