Composition for preventing, treating, or ameliorating mucositis comprising lactobacillus sakei CVL-001 strain

Abstract

The present invention relates to a composition for preventing, treating, or ameliorating mucositis, comprising a Lactobacillus sakei CVL-001 strain. Both live and inactivated cells of the Lactobacillus sakei CVL-001 strain exhibit an effect of alleviating symptoms related to mucositis induced by anticancer chemotherapy or radiotherapy performed to treat cancer, and can therefore be effectively used for the prevention, treatment, or amelioration of mucositis.

Description

Composition for preventing, treating or improving mucositis comprising Lactobacillus sakei CVL-001 strain

[0001] The present invention was made under the support of the Ministry of SMEs and Startups under the task identification number 1425182132 and the detailed task number 00302467. The research management specialized organization of the task is the Korea Technology Information Promotion Agency for Small and Medium Businesses, the research project name is "Startup Growth Technology Development Project (TIPS)", the research project name is "Development of a Probiotic-Based Anticancer-Induced Mucositis Preventive Treatment", the main organization is Nodecure Co., Ltd., and the research period is 2023.07.01 - 2026.06.30.

[0002] In addition, the present invention was made with the support of the Ministry of Science and ICT under the task identification number 1711184598 and the detailed task number 2022R1A2C2012287. The research management specialized institution of the said task is the National Research Foundation of Korea, the research project name is "Individual Basic Research (Ministry of Science and ICT)", the research project name is "Study on the disease control mechanism of probiotics through regulation of node-like receptor signal", the main institution is Chonnam National University Industry-Academic Cooperation Foundation, and the research period is 2022.03.01-2027.02.28.

[0003] This patent application claims priority to Republic of Korea Patent Application No. 10-2024-0082479, filed with the Korean Intellectual Property Office on June 25, 2024, the disclosure of which is incorporated herein by reference.

[0004] The present invention relates to a composition for preventing, treating or improving mucositis comprising a Lactobacillus sakei CVL-001 strain, and more particularly, to a technique for preventing, treating or improving mucositis caused by anticancer chemotherapy or radiotherapy performed to treat cancer using live or killed cells of the Lactobacillus sakei CVL-001 strain.

[0005] The incidence of cancer is steadily increasing worldwide. According to a report by the World Cancer Research Fund International, the number of cancer cases worldwide in 2020 is estimated at 18.1 million. The mortality rate from cancer is also steadily increasing. According to the Ministry of Health and Welfare, the cancer mortality rate in Korea was 160.1 deaths per 100,000 people in 2020. According to a report by World Wide Statistics, an estimated 10 million people died from cancer worldwide in 2020. The number of cancer patients is increasing due to changes in population, health ecology, and environmental structures, and the number of cancer patients and deaths is expected to increase due to the rapid aging of the population.

[0006] There are two methods for treating cancer: chemotherapy using drugs and radiation therapy using high-energy radiation. Most cancer treatments affect normal cells as well as cancer cells, causing side effects. Various types of side effects appear in the brain, head and neck, breasts, chest, abdomen, colon, and pelvic areas.

[0007] A common side effect of chemotherapy or radiation therapy is mucositis. Mucositis is caused by toxicity resulting from damage to the digestive tract mucosal cells, most commonly affecting the small intestine. It can also occur in the esophagus, stomach, and colon. Recently, mucositis caused by chemotherapy or radiation therapy has emerged as a serious side effect. The epithelial cells of the oral cavity and gastrointestinal tract are the fastest-growing tissues in the body, replacing themselves every 7 to 14 days. The small intestine, in particular, has a particularly rapid turnover cycle, with epithelial cells being replaced approximately every seven days. Chemotherapy or radiation therapy interferes with mucosal cell regeneration, further exacerbating mucositis.

[0008] Adjuvant chemotherapy is a drug used in conjunction with other cancer treatments to enhance the overall efficacy of the treatment. It is not intended as a monotherapy, but rather as a companion treatment to other cancer treatments such as surgery, chemotherapy, and radiation therapy. Adjuvant chemotherapy helps reduce side effects that can occur after chemotherapy, such as nausea, vomiting, and mucositis. However, there is no treatment for mucositis, a serious side effect, so several companies are working on developing treatments for mucositis.

[0009] Accordingly, the inventors of the present invention administered live or killed Lactobacillus sakei CVL-001 strain to an animal model of mucositis induced by cisplatin administration or radiation exposure, and confirmed the effects of restoration of the length of the small intestine, restoration of the length of small intestinal villi, promotion of proliferation of small intestinal epithelial cells, increase in survival rate, and restoration of the number of intestinal crypts and small intestinal villi.

[0010] Accordingly, the purpose of the present invention is to provide a pharmaceutical composition for preventing or treating mucositis containing a Lactobacillus sakei strain.

[0011] Another object of the present invention is to provide a food composition for improving mucositis, comprising a Lactobacillus sakei strain.

[0012] Another object of the present invention relates to the use of Lactobacillus sakei strains for preventing, treating or improving mucositis.

[0013] The present invention relates to a composition for preventing, treating or improving mucositis comprising a Lactobacillus sakei CVL-001 strain, wherein live or dead cells of the Lactobacillus sakei CVL-001 strain according to the present invention exhibit an effect of preventing, treating or improving mucositis caused by anticancer chemotherapy or radiotherapy performed to treat cancer.

[0014] The present inventors administered live or killed Lactobacillus sakei CVL-001 strain to an animal model of mucositis induced by cisplatin administration or radiation irradiation, and confirmed the effects of restoration of the length of the small intestine, restoration of the length of small intestinal villi, promotion of proliferation of small intestinal epithelial cells, increase in survival rate, and restoration of the number of intestinal crypts and small intestinal villi.

[0015] Hereinafter, the present invention will be described in more detail.

[0016] Another aspect of the present invention is a pharmaceutical composition for preventing or treating mucositis comprising a Lactobacillus sakei strain.

[0017] In the present invention, the strain may be the Lactobacillus sakei CVL-001 strain deposited under the accession number KCTC13816BP.

[0018] In the present invention, the strain may be at least one selected from the group consisting of live cells, dead cells, lysates thereof, and extracts thereof.

[0019] The above-mentioned dead cells may be killed by heat treatment under temperature conditions of 70°C to 140°C for 5 to 120 minutes, and preferably, may be killed by heat treatment under temperature conditions of 90°C to 100°C for 20 to 30 minutes, but are not limited thereto.

[0020] The pharmaceutical composition may contain the strain at a concentration of 0.1 to 100 mg / ml, preferably 0.1 to 50 mg / ml, 0.1 to 20 mg / ml, 0.1 to 10 mg / ml, 0.1 to 5 mg / ml, 0.1 to 2 mg / ml, 0.5 to 100 mg / ml, 0.5 to 50 mg / ml, 0.5 to 20 mg / ml, 0.5 to 10 mg / ml, 0.5 to 5 mg / ml, 0.5 to 2 mg / ml, 0.8 to 100 mg / ml, 0.8 to 50 mg / ml, 0.8 to 20 mg / ml, 0.8 to 10 mg / ml, or 0.8 to 5 mg / ml, for example, at a concentration of 0.8 to 2 mg / ml. It may be, but is not limited to,

[0021] The daily dosage of the strain per 1 kg of the subject's body weight may be 0.002 to 20 mg, preferably 0.002 to 10 mg, 0.002 to 5 mg, 0.002 to 2 mg, 0.002 to 1 mg, 0.002 to 0.5 mg, 0.002 to 0.2 mg, 0.02 to 20 mg, 0.02 to 10 mg, 0.02 to 5 mg, 0.02 to 2 mg, 0.02 to 1 mg, 0.02 to 0.5 mg, 0.02 to 0.2 mg, 0.2 to 20 mg, 0.2 to 10 mg, 0.2 to 5 mg, 0.2 to 2 mg, or 0.2 to 1 mg, for example, 0.2 to 0.5 It may be mg, but is not limited to this.

[0022] The term “subject” in this specification means an object to be administered or treated, and may preferably be a mammal, and may be selected from the group consisting of, but not limited to, a mouse, a rat, a monkey, a dog, a cat, a cow, a rabbit, a horse, a pig, and a human.

[0023] The daily dose per 1 kg of body weight of the above strain is 5 X 10 7 5 X 10 15 It may be CFU, preferably 5 X 10 7 5 X 10 13 CFU, 5 X 10 7 5 X 10 11 CFU, 5 X 10 7 5 X 10 10 CFU, 5 X 10 8 5 X 10 15 CFU, 5 X 10 8 5 X 10 13 CFU, 5 X 10 8 5 X 10 11 CFU, 5 X 10 8 5 X 10 10 CFU, 5 X 10 10 5 X 10 15 CFU, or 5 X 10 10 5 X 10 13 It could be CFU, for example, 5 X 10 10 5 X 10 11 It may be, but is not limited to, CFU.

[0024] In the present invention, the mucositis may be caused by anticancer chemotherapy or radiation therapy.

[0025] In the present invention, the mucositis may be selected from the group consisting of oral mucositis, esophageal mucositis, gastric mucositis, small intestinal mucositis, large intestinal mucositis, colonic mucositis, rectal mucositis, and anal mucositis.

[0026] The pharmaceutical composition of the present invention can be used as a pharmaceutical composition comprising a pharmaceutically effective amount of the strain or a pharmaceutically acceptable carrier.

[0027] The term “pharmaceutically effective amount” as used herein means an amount sufficient to achieve the efficacy or activity of the strain described above.

[0028] Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are those commonly used in formulations, and include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like.

[0029] The pharmaceutical composition according to the present invention can be administered to mammals, including humans, via various routes. Any commonly used route of administration may be used, including oral, transdermal, intravenous, intramuscular, and subcutaneous administration, with oral administration being preferred.

[0030] The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity, and a skilled physician can easily determine and prescribe a dosage effective for the desired treatment or prevention.

[0031] The pharmaceutical composition of the present invention can be manufactured in a unit dosage form or can be manufactured by inserting it into a multi-dose container by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method that can be easily performed by a person having ordinary skill in the art to which the present invention pertains. In this case, the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or in the form of an extract, powder, granules, tablets, capsules or gel (e.g., hydrogel), and may additionally include a dispersing agent or stabilizer.

[0032] One aspect of the present invention is a food composition for improving mucositis comprising a Lactobacillus sakei strain.

[0033] In the present invention, the strain may be the Lactobacillus sakei CVL-001 strain deposited under the accession number KCTC13816BP.

[0034] In the present invention, the strain may be at least one selected from the group consisting of live cells, dead cells, lysates thereof, and extracts thereof.

[0035] The above-mentioned dead cells may be killed by heat treatment under temperature conditions of 70°C to 140°C for 5 to 120 minutes, and preferably, may be killed by heat treatment under temperature conditions of 90°C to 100°C for 20 to 30 minutes, but are not limited thereto.

[0036] The above food composition may be a health functional food composition or a general food composition.

[0037] The food composition may contain the strain at a concentration of 0.1 to 100 mg / ml, preferably 0.1 to 50 mg / ml, 0.1 to 20 mg / ml, 0.1 to 10 mg / ml, 0.1 to 5 mg / ml, 0.1 to 2 mg / ml, 0.5 to 100 mg / ml, 0.5 to 50 mg / ml, 0.5 to 20 mg / ml, 0.5 to 10 mg / ml, 0.5 to 5 mg / ml, 0.5 to 2 mg / ml, 0.8 to 100 mg / ml, 0.8 to 50 mg / ml, 0.8 to 20 mg / ml, 0.8 to 10 mg / ml, or 0.8 to 5 mg / ml, for example, 0.8 to 2 mg / ml. However, it is not limited to these.

[0038] In the present invention, the mucositis may be caused by anticancer chemotherapy or radiation therapy.

[0039] In the present invention, the mucositis may be selected from the group consisting of oral mucositis, esophageal mucositis, gastric mucositis, small intestinal mucositis, large intestinal mucositis, colonic mucositis, rectal mucositis, and anal mucositis.

[0040] When the food composition of the present invention is used as a food additive, the food composition may be added as is or used in combination with other foods or food ingredients, and may be used appropriately according to conventional methods. Generally, when manufacturing a food or beverage, the food composition of the present invention may be added in an amount of 15% by weight or less, preferably 10% by weight or less, relative to the raw materials.

[0041] There are no specific restrictions on the types of the above foods. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, foods, and vitamin complexes, and all foods in the conventional sense are included.

[0042] The above food may be selected from the group consisting of capsules, tablets, powders, granules, liquids, pills, syrups and bars.

[0043] The above beverage may contain various flavoring agents or natural carbohydrates as additional ingredients. The above-mentioned natural carbohydrates may include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, or synthetic sweeteners such as saccharin and aspartame. The proportion of the natural carbohydrates may be appropriately determined by those skilled in the art.

[0044] In addition to the above, the food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the food composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients may be used independently or in combination. The proportions of these additives may also be appropriately selected by those skilled in the art.

[0045] The present invention relates to a composition for preventing, treating or improving mucositis, comprising a Lactobacillus sakei CVL-001 strain. Live or dead cells of the Lactobacillus sakei CVL-001 strain exhibit an effect of alleviating symptoms related to mucositis caused by anticancer chemotherapy or radiotherapy performed to treat cancer, and thus can be effectively used for preventing, treating or improving mucositis.

[0046] Figure 1 is a schematic diagram showing the administration schedule of four types of lactic acid bacteria and cisplatin according to one embodiment of the present invention.

[0047] Figure 2 is a graph showing changes in the length of the small intestine due to administration of four types of lactic acid bacteria from a cisplatin-induced mucositis animal model according to one embodiment of the present invention.

[0048] FIG. 3 is a photograph comparing the length of small intestinal villi and the degree of recovery of intestinal crypts by administration of four types of lactic acid bacteria through hematoxylin and eosin (H&E) staining of small intestinal tissue samples from an animal model of cisplatin-induced mucositis according to one embodiment of the present invention.

[0049] Figure 4 is a schematic diagram showing the administration schedule of Lactobacillus sakei CVL-001 strain and cisplatin according to one embodiment of the present invention.

[0050] Figure 5a is a photograph showing changes in the length of the small intestine from a cisplatin-induced mucositis animal model according to one embodiment of the present invention.

[0051] Figure 5b is a graph showing changes in the length of the small intestine from a cisplatin-induced mucositis animal model according to one embodiment of the present invention.

[0052] Figure 6a is a photograph showing changes in the length of small intestinal villi from a small intestinal tissue sample of an animal model of cisplatin-induced mucositis according to one embodiment of the present invention.

[0053] Figure 6b is a graph showing changes in the length of small intestinal villi from a small intestinal tissue sample of an animal model of cisplatin-induced mucositis according to one embodiment of the present invention.

[0054] Figure 7 is a schematic diagram showing the schedule for administering Lactobacillus sakei CVL-001 killed cells and irradiating them according to one embodiment of the present invention.

[0055] Figure 8 is a graph showing the survival rate by group of an animal model of radiation-induced mucositis according to one embodiment of the present invention.

[0056] Figure 9a is a photograph of a small intestine tissue specimen of an animal model of radiation-induced mucositis according to one embodiment of the present invention.

[0057] Figure 9b is a graph showing the recovery pattern of lost intestinal crypts from a small intestinal tissue sample of an animal model of radiation-induced mucositis according to one embodiment of the present invention.

[0058] Figure 9c is a graph showing changes in the number of small intestinal villi from a small intestinal tissue sample of an animal model of radiation-induced mucositis according to one embodiment of the present invention.

[0059] Figure 10 is a photograph showing whether cell proliferation is observed in a small intestine tissue sample of an animal model of radiation-induced mucositis according to one embodiment of the present invention.

[0060] The present invention relates to a pharmaceutical composition for preventing or treating mucositis comprising a Lactobacillus sakei strain.

[0061] Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these examples are intended only to illustrate the present invention, and the scope of the present invention is not limited by these examples.

[0062] Throughout this specification, "%" used to indicate the concentration of a particular substance is (wt / wt)% for solid / solid, (wt / vol)% for solid / liquid, and (vol / vol)% for liquid / liquid, unless otherwise stated.

[0063] Unless otherwise specifically defined herein, all scientific and technical terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.

[0064]

[0065] Example 1: Cultivation of Lactobacillus sakei CVL-001

[0066] Lactobacillus sakei CVL-001 (KCTC13816BP), Lactobacillus kunkeei NCHBL-003 (KCTC14908BP), Lactobacillus plantarum NCHBL-004 (KCTC14909BP), and Lactobacillus reuteri NCHBL-005 (KCTC15449BP) were prepared as lactic acid bacteria.

[0067] The lactic acid bacteria stock was spread on MRS agar, a selective medium for lactic acid bacteria, and cultured in an incubator at 30°C for 18 hours. Afterwards, a single colony was extracted and dissolved in MRS broth. The MRS broth was pre-cultured in an incubator at 30°C and 150 rpm for 12-16 hours. To obtain the optimal condition of the bacteria, the pre-cultured bacteria were main-cultured in fresh MRS broth in an incubator at 30°C and 150 rpm for 4-6 hours. Afterwards, the bacteria were harvested when the optical density was 0.6, which was the point at which the activity of the bacteria was the highest, through absorbance measurement.

[0068] The live lactic acid bacteria were washed using PBS through centrifugation and then administered using PBS as a solvent. The dead lactic acid bacteria were washed using PBS through centrifugation and then killed by applying heat at 100°C for 30 minutes, and then lyophilized and administered using PBS as a solvent.

[0069]

[0070] Example 2: Confirmation of the protective effect of Lactobacillus sakei CVL-001 strain dead cells in an animal model of mucositis implemented using the anticancer drug cisplatin.

[0071] 2-1. Experimental method

[0072] Seven-week-old C57BL / 6 mice were purchased and divided into five groups, and the average body weight (approximately 20 g) was matched to reduce the variation between experimental groups. After acclimatization for 7 days after introduction of the mice, 0.2 ml (10 mg / kg) of the four types of killed lactic acid bacteria dissolved in PBS at a concentration of 1 mg / ml was administered orally once daily for 6 days as shown in Fig. 1. Water and food were provided ad libitum to all experimental groups.

[0073] Group 1: PBS (lactic acid bacteria solvent) (Control)

[0074] Group 2: Cisplatin (disease group) + PBS (lactic acid bacteria solvent) (Cisplatin)

[0075] Group 3: Cisplatin (disease group) + Lactobacillus sakei CVL-001 10 mg / kg

[0076] Group 4: Cisplatin (disease group) + Lactobacillus kunqi 10 mg / kg

[0077] Group 5: Cisplatin (disease group) + Lactobacillus plantarum 10 mg / kg

[0078] Group 6: Cisplatin (disease group) + Lactobacillus reuteri 10 mg / kg

[0079] Six days after administration of probiotics, cisplatin, an anticancer drug, was dissolved in normal saline at a concentration of 1 mg / ml and 0.6 ml (30 mg / kg) was administered intraperitoneally, and recovery was observed for 3 days. Probiotics were continuously administered until the end of the experiment.

[0080]

[0081] 2-2. Changes in the length and tissue index recovery of the small intestine

[0082] Intraperitoneal administration of cisplatin to mice induces mucositis similar to that in humans. Subsequent changes in body weight, clinical symptoms, and small intestinal length are observed. Previous reports have shown that the small intestine of mice administered cisplatin shortens during autopsy. Based on this, changes in small intestinal length were observed in the experimental group of mice administered the four types of lactic acid bacteria in Example 2-1.

[0083] Length of the 1st, 2nd, 3rd, 4th, 5th, and 6th groups (cm) 37.70 33.56 39.00 37.08 35.80 37.48

[0084] As can be seen in Table 1 and Figure 2, the results of this study confirmed that the length of the small intestine shortened by cisplatin was restored by administering Lactobacillus sakei CVL-001.

[0085] These small intestine tissues (jejunum) were prepared as tissue specimens using formalin, and hematoxylin and eosin (H&E) staining was performed according to the conventional method.

[0086] As can be seen in Figure 3, in the group administered Lactobacillus sakei CVL-001, the length of the small intestinal villi and the intestinal crypt were restored.

[0087]

[0088] Example 3: Confirmation of the protective effect of live and dead Lactobacillus sakei CVL-001 strain in an animal model of mucositis implemented using the anticancer drug cisplatin.

[0089] 3-1. Experimental method

[0090] Seven-week-old C57BL / 6 mice were purchased and separated into six groups, and the average body weight (approximately 20 g) was matched to reduce the variation between experimental groups. After acclimatization for 7 days after receiving the mice, 1 X 10 Lactobacillus sakei CVL-001 strain live and dead cells were inoculated into PBS as a solvent for 6 days, as shown in Fig. 4. 9 CFU / mouse was administered orally once a day, and water and food were provided ad libitum to all experimental groups.

[0091] Group 1: PBS (lactic acid bacteria solvent) (Control)

[0092] Group 2: Cisplatin (disease group) + PBS (lactic acid bacteria solvent) (Cisplatin)

[0093] Group 3: Cisplatin (disease group) + 1 x 10 Lactobacillus sakei CVL-001 live bacteria 9 CFU (CVL-001 Live)

[0094] Group 4: Cisplatin (disease group) + 1 x 10 killed Lactobacillus sakei CVL-001 cells 9 CFU (CVL-001 HK)

[0095] Six days after administration of lactic acid bacteria, cisplatin, an anticancer drug, was dissolved in saline at a concentration of 1 mg / ml using the same method as in Example 2-1, and 0.6 ml (30 mg / kg) was administered intraperitoneally, and the recovery trend was observed for 3 days. Lactic acid bacteria were continuously administered until the end of the experiment.

[0096]

[0097] 3-2. Changes in the length and tissue index recovery of the small intestine

[0098] From the experimental group mice of the above Example 3-1, the small intestines of representative individuals were listed by group, and small intestine tissue samples were made by performing the same method as in the above Example 2-2, and changes in the length of the small intestine and the length of the small intestine villi were confirmed through H&E staining.

[0099] Length of the 1st, 2nd, 3rd, and 4th military units (cm) 39.40 36.36 38.78 38.68

[0100] As can be seen in Table 2, Figures 5a and 5b, the results of this study confirmed that the length of the small intestine shortened by cisplatin was restored by administering live or killed Lactobacillus sakei CVL-001.

[0101] Length of villi of the 1st, 2nd, 3rd, and 4th groups (μm) 482.24 188.7 124 0.43 23 9.54

[0102] In addition, as can be seen in Table 3, Figures 6a and 6b, the length of the small intestinal villi was restored in the group administered live or dead Lactobacillus sakei CVL-001.

[0103]

[0104] Example 4: Confirmation of the protective effect of killed Lactobacillus sakei CVL-001 strain in an animal model of radiation-induced mucositis.

[0105] 4-1. Experimental method

[0106] Seven-week-old C57BL / 6 mice were purchased and separated into 10 groups per experimental group. To reduce the variation between experimental groups, the average body weight (approximately 20 g) was matched to separate them. After acclimatization for 7 days after receiving the mice, 1 X 10 of the Lactobacillus sakei CVL-001 strain was inoculated into each group using PBS as a solvent for 9 days, as shown in Fig. 7. 7 CFU / mouse, 1 X 10 9 CFU / mouse was administered orally once a day, and water and food were provided ad libitum to all experimental groups.

[0107] Group 1: PBS (lactic acid bacteria solvent) (Control)

[0108] Group 2: Irradiation (disease group) + PBS (lactic acid bacteria solvent) (IR)

[0109] Group 3: Radiation exposure (disease group) + 1 x 10 killed Lactobacillus sakei CVL-001 cells 7 CFU (IR + CVL-001 10 7 )

[0110] Group 4: Radiation exposure (disease group) + 1 x 10 killed Lactobacillus sakei CVL-001 cells 9 CFU (IR + CVL-001 10 9 )

[0111] Tissue indices were determined from 5 out of 10 animals per experimental group, and survival rates were determined from 5 animals. On the 9th day after administration of probiotics, irradiation (IR) was performed to an absorbed dose of 15 Gy, and body weight and survival rate were checked. Probiotics were continuously administered until the end of the experiment.

[0112]

[0113] 4-2. Confirmation of improvement in survival rate reduction

[0114] Known causes of decreased survival after radiation include destruction of the hematopoietic system, destruction of intestinal epithelial cells, bacterial infection and toxemia, and dehydration due to diarrhea. We investigated whether administration of Lactobacillus sakei CVL-001 improved survival.

[0115] As can be seen in Figure 8, in group 2 (IR), which is the radiation exposure group, dead individuals were confirmed from 3 to 4 days after radiation exposure, and all individuals were confirmed dead on the 6th to 7th day, but Lactobacillus sakei CVL-001 1 X 10 9 Group 4 (IR + CVL-001 10) 9 ) was ultimately shown to have a survival rate of 60%.

[0116]

[0117] 4-3. Confirmation of tissue index recovery and cell proliferation

[0118] From the experimental group mice of Example 4-1, small intestinal tissue samples were prepared by performing the same method as in Example 2-2, and changes in the number of intestinal crypts and small intestinal villi were confirmed. In addition, cell proliferation of small intestinal epithelial cells was confirmed through Ki-67 staining, a cell proliferation marker (Ki67 (MKI67) Rabbit monoclonal antibody, clone SP6; DRM004, Acris Antibodies GmbH, Herford, Germany).

[0119] Number of intestinal villi in group 1, group 2, group 3, and group 4: 127, 205, 2013, 55, 17, 80, and 38, 12, 27, 67, 32, 72, 34, 60

[0120] As can be seen in Table 4 and Figures 9a to 9c, the number of intestinal crypts and villi lost due to radiation exposure was found to be restored by administration of Lactobacillus sakei CVL-001.

[0121] Additionally, as can be confirmed in Fig. 10, the administration of Lactobacillus sakei CVL-001 to small intestinal epithelial cells destroyed by radiation exposure resulted in the induction of cell proliferation.

[0122] The present invention relates to a composition for preventing, treating or improving mucositis comprising a Lactobacillus sakei CVL-001 strain, and more particularly, to a technique for preventing, treating or improving mucositis caused by anticancer chemotherapy or radiotherapy performed to treat cancer using live or killed cells of the Lactobacillus sakei CVL-001 strain.

[0123] [Accession number]

[0124] Name of depositor: Korea Research Institute of Bioscience and Biotechnology, Biological Resource Center (KCTC)

[0125] Accession number: KCTC13816BP

[0126] Date of acceptance: February 19, 2019

[0127]

Claims

1. A pharmaceutical composition for preventing or treating mucositis containing a Lactobacillus sakei strain.

2. A pharmaceutical composition according to claim 1, wherein the strain is a Lactobacillus sakei CVL-001 strain deposited under the accession number KCTC13816BP.

3. A pharmaceutical composition according to claim 1, wherein the strain is at least one selected from the group consisting of live cells, dead cells, lysates thereof, and extracts thereof.

4. A pharmaceutical composition according to claim 1, wherein the mucositis is caused by anticancer chemotherapy or radiation therapy.

5. A pharmaceutical composition according to claim 1, wherein the mucositis is selected from the group consisting of oral mucositis, esophageal mucositis, gastric mucositis, small intestinal mucositis, large intestinal mucositis, colonic mucositis, rectal mucositis, and anal mucositis.

6. In the first paragraph, the daily dose of the strain per 1 kg of the subject's body weight is 5 X 10 7 5 X 10 15 A pharmaceutical composition comprising CFU.

7. A food composition for improving mucositis containing a Lactobacillus sakei strain.

8. A food composition according to claim 7, wherein the strain is a Lactobacillus sakei CVL-001 strain deposited under the accession number KCTC13816BP.

9. A food composition according to claim 7, wherein the strain is at least one selected from the group consisting of live bacteria, dead bacteria, lysates thereof, and extracts thereof.

10. A food composition according to claim 7, wherein the mucositis is caused by anticancer chemotherapy or radiation therapy.

11. A food composition according to claim 7, wherein the mucositis is selected from the group consisting of oral mucositis, esophageal mucositis, gastric mucositis, small intestinal mucositis, large intestinal mucositis, colonic mucositis, rectal mucositis, and anal mucositis.

12. A food composition according to claim 7, wherein the food composition contains the strain at a concentration of 0.1 to 100 mg / ml.

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