Pharmaceutical composition comprising lactobacillus gasseri kbl697 strain in a dosage form with enteric coating and therapeutic use of said composition

Abstract

The present invention relates to a Lactobacillus gasseri KBL697 strain, food composition, feed or antifungal, external skin preparation, medical plaster, pharmaceutical composition and cosmetic composition comprising said strain and therapeutic use of said composition. The Lactobacillus gasseri KBL697 strain (accession no. KCTC 13520BP) according to the present invention attenuates allergic cell reactions, significantly improves the symptoms of atopic dermatitis and exhibits anti-inflammatory and antifungal effects and a therapeutic effect for intestinal diseases such as irritable bowel syndrome and colitis. Thus, the single strain alone can achieve all the objectives of alleviating allergic and inflammatory diseases and improving intestinal health, thus finding advantageous applications as a probiotic substance.Furthermore, based on its antifungal activity, the strain can be advantageously used in an external skin preparation against various skin diseases caused by fungi, and in a cosmetic composition and a functional adhesive for the relief of sensitive skin.

Description

1 / 46 “PHARMACEUTICAL COMPOSITION COMPRISING LACTOBACILLUS GASSERI KBL697 STRAIN IN AN ENTERIC-COATED DOSAGE FORM AND THERAPEUTIC USE OF SAID COMPOSITION” Technical Field

[001] The present invention relates to a strain of Lactobacillus gasseri KBL697 and its use. More specifically, the present invention relates to a functional health food composition having at least one effect selected from the group consisting of relief of allergic symptoms, relief of inflammatory symptoms, improvement of intestinal health and immunoregulation; an antifungal composition; and a pharmaceutical composition for the treatment of at least one disease selected from the group consisting of allergic diseases, inflammatory diseases, intestinal diseases and autoimmune diseases, comprising at least one selected from the group consisting of an innovative probiotic strain of Lactobacillus gasseri KBL697, cultures of said strain, lysates of said strain and extracts of said strain. Background of the Technique

[002] Probiotics refer to microorganisms and their resulting products having antimicrobial and enzymatic activities to help balance intestinal microorganisms. Furthermore, probiotics are also defined as live bacteria in the form of one or more strains to improve intestinal flora when provided to humans or animals in the form of dried cells or fermentation products. Probiotics must inhabit the human intestine, be non-pathogenic and non-toxic, and survive long enough to reach the intestine. Additionally, probiotics must maintain viability and activity until consumed in delivered food, be sensitive to antibiotics used to prevent infection, and not have antibiotic-resistant plasmids. Furthermore, probiotics must be resistant to acids, enzymes, and bile in the intestinal environment. Petition 870260037323, dated 04 / 22 / 2026, page 11 / 114 2 / 46

[003] These probiotics may include, for example, Bacillus sp. having an excellent capacity to produce digestive enzymes such as amylase, protease, lipase, cellulase and phosphatase, Lactobacillus sp. producing lactic acid and photosynthetic bacteria preventing odor by using odor-causing substances (such as ammonia, hydrogen sulfide and amines) that remain in animal feces in the metabolic process. Recently, probiotics have been reported as having several health function-enhancing effects, including improved gut health, and therefore highlighted as key therapeutic substances that can replace existing compound-based therapeutic agents.

[004] Meanwhile, allergy is a biochemical phenomenon that exhibits a unique and altered response to a foreign substance (antigen, allergen). The foreign substance that causes the symptoms is called an allergen, while the diseases resulting from these symptoms are called allergic diseases. Allergy is a pathological process in the living body resulting from the antigen-antibody reaction. In general, there are four types of allergy depending on the triggering period of the reaction and the involvement of complement. Type 1, among these, is the anaphylactic type (immediate type) in which the target organs are mainly digestive organs, skin and lungs, and common symptoms include gastrointestinal allergy, urticaria, atrophodermatitis, allergic rhinitis and bronchial asthma, etc.The pathological mechanism of Type 1 is known as follows: when antigens contact IgE antibodies attached to the surface of mast cells and basophilic leukocytes, the target cells are activated to secrete chemical transmitters such as histamine, leukotriene, and PAF, and then blood vessels and smooth muscles are constricted. This mechanism can often be combined with Type 4 (delayed type). In other words, this anaphylaxis and allergic reaction can arise due to a variety of alterations in mast cells, etc. The activation of mast cells, which leads to degranulation, is caused by the binding of antigen, anti-IgE, lectin, etc. to Fc receptors, the stimulation of... Petition 870260037323, dated 04 / 22 / 2026, page 12 / 114 3 / 46 anaphylatoxin, etc., or other drugs, such as calcium ionophore, compound 48 / 80, codeine and synthetic adrenocorticotropic hormone.

[005] Mast cells and basophilic leukocytes in the blood are known as the main cells in the body for causing various allergic diseases such as allergic rhinitis, allergic dermatitis, asthma, food allergy, and anaphylactic shock. These cells have receptors (FcRI) on their surfaces for IgE, which is an allergy-causing antibody, and the cells are stimulated by allergy-causing substances (antigen, allergen) to secrete their own allergy-causing substances out of the cells (Kim K et al, Eur J Pharmacol, 581: 191-203, 2008).

[006] Among allergic diseases, atopic dermatitis, widely known to the public, is a chronic recurrent skin disease that affects newborns or children and can persist into adulthood. Like asthma or allergic rhinitis, atopic dermatitis is an inflammatory skin disease associated with local infiltration of T lymphocytes that produce IL-4 and IL-5. IL-4, well known to the public, controls the development of the T helper 2 (Th2) phenotype, resulting in overproduction of immunoglobulins (Ig) and eosinophilia, and increased serum IgE levels. 80 to 90% of individuals with positive skin tests for food and inhalant allergens presented with atopic dermatitis.

[007] There are different treatments to treat or prevent allergic diseases and atopic dermatitis, but no effective treatment has yet been found. Some drug-based treatments are known, but even short-term administration of the drug for treatment would develop a tolerance, and long-term administration can cause serious side effects; therefore, such drug-based treatments for allergic diseases and atopic dermatitis have been avoided recently. Under these circumstances, without the treatment having any obvious and absolute effect, the irritating symptoms, such as itching and redness of the skin, in addition to allergies, often do not improve. Petition 870260037323, dated 04 / 22 / 2026, page 13 / 114 4 / 46

[008] Meanwhile, irritable bowel syndrome (IBS) is a symptom characterized by abdominal pain and / or irritation associated with altered bowel movements or bowel habits; such symptoms cannot be explained by anatomical or biochemical abnormalities. Common symptoms of IBS also include urinary urgency, abdominal distension, and a feeling of incomplete bowel movement. Consequently, IBS can be classified as a functional gastrointestinal disorder, encompassing conditions such as functional bloating, non-cardiac chest pain, non-ulcerative dyspepsia, and chronic constipation or diarrhea. In particular, in the case of IBS, since the related symptoms affect aspects of well-being and normal function of patients, the disease has a significant impact on morbidity and quality of life, in addition to abdominal pain and discomfort.

[009] Inflammatory bowel disease (IBD) is a condition in which abnormal chronic inflammation in the intestine repeatedly improves and relapses, encompassing all inflammatory bowel diseases, such as Crohn's disease, ulcerative colitis, or Behcet's disease, but not limited to these. Much research has been conducted in the field of drug development to treat IBS and IBD. In this regard, several antidepressants are commonly used, although their efficacy in clinical trials is moderate and their clinical utility is limited due to significant side effects. Serotonergic drugs have also demonstrated efficacy against the general symptoms of IBS. However, the application of these drugs has been restricted in various ways due to several recent safety concerns. Consequently, there is a growing interest in the development of a new therapeutic agent for IBS.

[010] WO 96 / 29083 and EP 554418 disclose two types of Lactobacillus strains that form colonies in the intestine, namely, Lactobacillus plantarum 299v (DSM 6595) and Lactobacillus casei ssp. rhamnosus 271 (DSM 6594), etc. Document EP 415941 discloses a method for preparing a nutrient composition, Petition 870260037323, dated 04 / 22 / 2026, page 14 / 114 5 / 46 comprising the treatment of oatmeal porridge with enzymes before mixing it with lactobacilli. US Patent No. 7195906 discloses a strain of Bifidobacterium isolated from the desiccated and washed human gastrointestinal tract for the treatment of inflammatory diseases, especially gastrointestinal inflammatory activity, such as IBD and IBS.

[011] However, no strain possesses excellent effects in improving intestinal health, for example, the treatment of IBD and IBS, and in order to find strains possessing such effects, many research institutions are working on this.

[012] Under these circumstances, the present inventors dedicated themselves to studies of probiotics to find a way to replace drug-based treatments for allergic diseases, including atopic dermatitis, which have no satisfactory treatments. And, therefore, the present invention was completed by confirming that an innovative strain of Lactobacillus gasseri showed excellent therapeutic effects in allergic diseases, such as atopic dermatitis, and further confirming that said strain also showed superior effects in antifungal activity, intestinal health, immunoregulation and inhibition of inflammation. Summary of the Invention

[013] The objective of the present invention is to provide an innovative strain showing excellent effects in relieving allergic symptoms, such as atopic dermatitis, relieving inflammatory symptoms, antifungal activity, improving intestinal health and immune regulation, and a variety of its uses.

[014] In order to achieve the objective, the present invention provides the Lactobacillus gasseri KBL697 strain (Accessory No. KCTC 13520BP).

[015] In addition, the present invention provides a food composition or food additive composition comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain. Petition 870260037323, dated 04 / 22 / 2026, page 15 / 114 6 / 46

[016] The present invention provides a feed composition or feed additive composition comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain.

[017] The present invention also provides an antifungal composition, such as an anti-dandruff composition, comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain.

[018] The present invention also provides a pharmaceutical composition for the treatment of allergic diseases, such as atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases, comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain.

[019] The present invention also provides a method for treating allergic diseases, including atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases, comprising administering at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain to a subject in need thereof.

[020] The present invention also provides a composition comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain, for use in the prevention or treatment of allergic diseases, including atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases.

[021] The present invention also provides the use of a composition for the preparation of a preventive or therapeutic drug for allergic diseases, including atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases, comprising at least one selected from the group consisting of Petition 870260037323, dated 04 / 22 / 2026, page 16 / 114 7 / 46 said strain, cultures of said strain, lysates of said strain and extracts of said strain.

[022] The present invention also provides a cosmetic composition comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain.

[023] The present invention also provides a cosmetic adhesive or a medical adhesive comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain. Brief Description of the Drawings

[024] FIG. 1 illustrates the result that confirms the inhibitory effect of IL-4 expression by several Lactobacillus strains including Lactobacillus gasseri KBL697 strain, after induction of allergic reaction in EL4 cell lines.

[025] FIG. 2 illustrates the result that confirms the inhibitory effect of IL-5 expression by several Lactobacillus strains including Lactobacillus gasseri KBL697 strain, after induction of allergic reaction in EL4 cell lines.

[026] FIG. 3 illustrates the result that confirms an inhibitory effect on histamine secretion by treatment of various strains of Lactobacillus gasseri and an antihistamine agent ketotifen, after inducing histamine production by antigen-antibody reaction in RBL 2H3 cell lines.

[027] FIG. 4 illustrates the result of observing the remarkable effect of increasing the amount of secretion of the anti-inflammatory immunoregulatory cytokine IL-10 by treating the KBL697 strain, when treated with Lactobacillus gasseri strains after inducing the inflammatory reaction in RAW 264.7 cell lines.

[028] FIG. 5 illustrates the result that confirms the remarkable immunoregulatory and anti-inflammatory effect of treating the KBL697 strain with an ILW / TNF-α value, when treated with Lactobacillus gasseri strains after inducing the inflammatory reaction in RAW 264.7 cell lines.

[029] FIG. 6 illustrates the result that confirms the remarkable effect Petition 870260037323, dated 04 / 22 / 2026, p. 17 / 114 8 / 46 immunoregulatory and anti-inflammatory by treating the KBL697 strain with an IL-10 / IL-6 value, when treated with Lactobacillus gasseri strains after inducing inflammatory responses in RAW 264.7 cell lines.

[030] FIG. 7 illustrates the result of a spot test that confirms the antifungal activity of the Lactobacillus gasseri KBL697 strain.

[031] FIG. 8 illustrates the result that confirms the effect of reducing the dermatitis score by oral administration of the Lactobacillus gasseri KBL697 strain to mouse models in which atopic dermatitis was induced.

[032] FIG. 9 illustrates the result that confirms the itching-relieving effect of oral administration of the Lactobacillus gasseri KBL697 strain to mouse models in which atopic dermatitis was induced.

[033] FIG. 10 illustrates the result that confirms the ear thickness reduction effects of oral administration of the Lactobacillus gasseri KBL697 strain to mouse models in which atopic dermatitis was induced.

[034] FIG. 11 illustrates the result that confirms the skin thickness reduction effect of oral administration of the Lactobacillus gasseri KBL697a strain in mouse models in which atopic dermatitis was induced.

[035] FIG. 12 illustrates the result that confirms the effect of reducing blood IgE concentration by oral administration of the Lactobacillus gasseri KBL697a strain in mouse models in which atopic dermatitis was induced.

[036] FIG. 13 illustrates the result of a TEER assay that confirms the effect of strengthening airtight junctions by the Lactobacillus gasseri KBL697 strain.

[037] FIG. 14 illustrates the result of observing the body weight recovery effect by oral administration of the Lactobacillus gasseri KBL697 strain in 1 x 109CFU to mouse models in which colitis was induced.

[038] FIG. 15 illustrates the result of observing the effect of large intestine length recovery by oral administration of the Lactobacillus strain. Petition 870260037323, dated 04 / 22 / 2026, p. 18 / 114 9 / 46 gasseri KBL697a mouse models in which colitis was induced.

[039] FIG. 16 illustrates the result of observing the relief effect of PASI (Psoriasis Area and Severity Index) and edema symptoms by the Lactobacillus gasseri KBL697 strain in mouse models in which psoriasis was induced.

[040] FIG. 17 illustrates the result of determining the effect of reducing inflammatory cytokines (TNF-α, IFN-γ, IL-17) by the Lactobacillus gasseri KBL697 strain in mouse models in which psoriasis was induced.

[041] FIG. 18 illustrates the result of comparing the effect of body weight and large intestine length recovery by the Lactobacillus gasseri KBL697e infliximab strain to mouse models in which colitis was induced. Best Way to Implement the Invention

[042] Unless defined otherwise, all technical and scientific terms used in this descriptive report mean the same as understood by a person with ordinary skills in the art (“those skilled in the art”). In general, the nomenclature used in this descriptive report is well known in the art and commonly used.

[043] The present invention has discovered an anti-allergic effect of microorganisms derived from the human body and has selected the Lactobacillus gasseri KBL697 strain (Accessory No. KCTC 13520BP) with excellent allergy-inhibiting effects. 16S rDNA analysis of said strain demonstrates that said strain is a novel strain never before known to the public.

[044] According to one embodiment of the present invention, the present invention relates to an innovative probiotic strain of Lactobacillus gasseri KBL697 (KCTC Accession No. 13520BP), and said strain is characterized by comprising the 16S rDNA sequence of SEQ ID NO: 1.

[045] <SEQ ID NO: 1 > 16S rDNA sequence of a Lactobacillus strain Petition 870260037323, dated 04 / 22 / 2026, p. 19 / 114 10 / 46 gasseri KBL697 (Access No. KCTC 13520BP) GGCAAGTGGGCGGCGTGCTATACATGCAGTCGAGCGAGCTTGCCTAGA TGAATTTGGTGCTTGCACCAAATGAAACTAGATACAAGCGAGCGGCGGACGGG TGAGTAACACGTGGGTAACCTGCCCAAGAGACTGGGATAACACCTGGAAACAG ATGCTAATACCGGATAACAACACTAGACGCATGTCTAGAGTTTAAAAGATGGTTC TGCTATCACTCTTGGATGGACCTGCGGTGCATTAGCTAGTTGGTAAGGCAACGG CTTACCAAGGCAATGATGCATAGCCGAGTTGAGAGACTGATCGGCCACATTGG GACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTAGGGAATCTTCCAC AATGGACGCAAGTCTGATGGAGCAACGCCGCGTGAGTGAAGAAGGGTTTCGGC TCGTAAAGCTCTGTTGGTAGTGAAGAAAGATAGAGGTAGTAACTGGCCTTTATTT GACGGTAATTACTTAGAAAGTCACGGCTAACTACGTGCCAGCAGCCGCGGTAAT ACGTAGGTGGCAAGCGTTGTCCGGATTTATTGGGCGTAAAGCGAGTGCAGGCG GTTCAATAAGTCTGATGTGAAAGCCTTCGGCTCAACCGGAGAATTGCATCAGAA ACTGTTGAACTTGAGTGCAGAAGAGGAGAGTGGAACTCCATGTGTAGCGGTGG AATGCGTAGATATATGGAAGAACACCAGTGGCGAAGGCGGCTCTCTGGTCTGC AACTGACGCTGAGGCTCGAAAGCATGGGTAGCGAACAGGATTAGATACCCTGG TAGTCCATGCCGTAAACGATGAGTGCTAAGTGTTGGGAGGTTTCCGCCTCTCAG TGCTGCAGCTAACGCATTAAGCACTCCGCCTGGGGAGTACGACCGCAAGGTTG AAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCAGTGCAAACCTAAG AGATTAGGAGTTCCCTTCGGGGACGCTGAGACAGGTGGTGCATGGCTGTCGTC AGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTC ATTAGTTGCCATCATTAAGTTGGGCACTCTAATGAGACTGCCGGTGACAAACCG GAGAAAGGTGGGGATGACGTCAAGTCATCATGCCCCTTATGACCTGGGCTACA CACGTGCTACAATGGACGGTACAACGAGAAGCGAACCTGCGAAGGCAAGCGGA TCTCTGAAAGCCGTTCTCAGTTCGGACTGTAGGCTGCAACTCGCCTACACGAAG CTGGAATCGCTAGTAATCGCGGATCAGCACGCCGCGGTGAATACGTTCCCGGG Petição 870260037323, de 22 / 04 / 2026, pág. 20 / 114 11 / 46 CCTTGTACACACCGCCCGTCACACCATGAGAGTCTGTAACACCCAAAGCCGGT GGGATAACCTTTATAGGAGTCAGCCGTCTAAGTAGACAGATGTTA

[046] Subsequently, the present invention conducted experiments regarding the efficacy of said strain and thus verified that this strain has an excellent inhibitory effect on allergies, such as atopic dermatitis, relieves the inflammatory reaction and has antifungal activity, immunoregulatory properties and therapeutic effects on intestinal diseases. Furthermore, the inventors confirmed that said effects can be provided not only in the condition of live bacteria, but also under low-temperature sterilization or high-temperature sterilization.

[047] Accordingly, in another embodiment of the present invention, the present invention relates to a food composition or food additive composition comprising at least one selected from the group consisting of Lactobacillus gasseri KBL697 strain (Accessory No. KCTC 13520BP), cellular components of said strain, cultures of said strain, lysates of said strain and extracts of said strain.

[048] The composition can be characterized as a functional food composition for health with at least one effect selected from the group consisting of relief of allergic symptoms, such as atopic dermatitis, relief of inflammatory symptoms, improvement of intestinal health and immunoregulation.

[049] The said food composition or food additive composition can be readily used as an effective food for the relief of allergic symptoms, such as atopic dermatitis, relief of inflammatory symptoms, improvement of intestinal health and / or immunoregulation and for their prevention, for example, as main or minor ingredients of foods, food additives, healthy functional food compositions or functional drinks, but not limited to these.

[050] The term “food composition” refers to a natural or artificial product comprising at least one nutrient and, more preferably, refers Petition 870260037323, dated 04 / 22 / 2026, page 21 / 114 12 / 46 refers to a product that has become edible through a specific processing method, generally encompassing all foods, food additives, healthy functional foods, and functional beverages.

[051] The food that may comprise said food composition according to the present invention as an additive may include, for example, different types of food, beverages, chewing gum, tea, vitamin complex or functional food.Furthermore, the food of the present invention includes special nutritional foods (e.g., modified milk, children's / baby food), processed meat products, fish meat products, tofu, muk, noodles (e.g., ramen, Asian noodles), bakery products, health food supplements, seasoning products (e.g., soy sauce, soy paste, red pepper paste, mixed paste), sauces, confectionery (e.g., snacks), sweets, chocolates, chewing gum, ice cream, dairy products (e.g., fermented milk, cheese), other processed foods, kimchi, savory foods (e.g., different types of kimchi, pickled foods), beverages (e.g., fruit juice, vegetable juice, soy milk, fermented beverages), and natural seasonings (e.g., ramen broth powder), but not limited to these. Said foods, beverages, or food additives may be prepared in conventional ways.

[052] The term “functional health food” is a group of foods to which value is added so that its function is exercised and expressed for a predetermined purpose, using physical, biochemical or bioengineering techniques, or a processed food designed so that the in vivo adjustment functions of the relevant food composition, such as rhythm adjustment in prophylaxis, disease prevention and disease recovery, are sufficiently expressed. Such functional food may comprise food supplement additives that are scientifically acceptable in food terms and may comprise Petition 870260037323, dated 04 / 22 / 2026, page 22 / 114 13 / 46 additionally suitable carriers, excipients and diluents, which are normally used in its manufacture.

[053] The term “functional beverages”, as used in the present invention, refers collectively to beverage products for thirst quenching or for flavoring. There is no special limitation to these, except that, as essential ingredients in the indicated proportion, a composition for the relief of allergic symptoms such as atopic dermatitis, the relief of inflammatory symptoms, improvement of intestinal health and / or immunoregulation and the prevention thereof must be included in the beverages, and various flavoring agents or natural carbohydrates may be contained therein as additional ingredients as in common beverages.

[054] In addition to the above, the food comprising the food composition or food additive composition according to the present invention may contain various nutrients, vitamins, minerals (electrolyte), flavoring agents, such as synthetic flavoring agents and natural flavoring agents, coloring agents and fillers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickening agents, pH control agents, stabilizing agents, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages and the like, and each of the above ingredients may be used alone or in combination with one another.

[055] In food comprising the food composition according to the present invention, the composition of the present invention may comprise an amount of 0.001% by weight to 100% by weight and, preferably, 1% by weight to 99% by weight, based on the total weight of the food; in the case of beverages, it may comprise an amount of 0.001 g to 10 g, preferably 0.01 g to 1 g, in relation to 100 ml. For prolonged ingestion for health and hygiene purposes or for health monitoring, however, the amount may be below the above range; and since the effective ingredients have no problem in terms of safety profile, Petition 870260037323, dated 04 / 22 / 2026, page 23 / 114 14 / 46 which can be used in quantities above the range and which are not limited to the wide quantity mentioned above.

[056] The food composition according to the present invention may comprise the Lactobacillus gasseri KBL697 strain alone or in combination with an acceptable carrier, or may be prepared in the form of a composition suitable for human or animal consumption. That is, the composition may be added to food that does not contain probiotic bacteria or some probiotic bacteria. For example, microorganisms that may be used in combination with the strain according to the present invention in the preparation of the food of the present invention must be suitable for human or animal consumption and have probiotic activities to inhibit harmful pathogenic bacteria or to improve the balance of microorganisms in the intestinal tract of mammals after ingestion, but not limited to these.Such probiotic microorganisms may include, for example, yeasts such as Saccharomyces, Candida, Pichia or Torulopsis, fungi such as Aspergillus, Rhizopus, Mucor or Penicillium and bacteria belonging to the genus Lactobacillus, Bifidobacterium, Leuconosteptoc, Lactococcus, Bacillocus, Propionibacterium, Enterococcus or Pediococcus. Specifically suitable probiotic microorganisms may include, for example, Saccharomyces cerevisiae, Bacillus coagulans, Bacillus licheniformis, Bacillus subtilis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Enterococcus faecium, Enterococcus faecalis, Lactobacillus acidophilus, Lactobacillus alimentarius, Lactobacillus casei, Lactobacillus curvatus, Lactobacillus delbruckii, Lactobacillus johnsonii, Lactobacillus farciminus, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus sakei, Lactocococcus lactis or Pediococcus acidilacticis.Preferably, the food composition according to the present invention may further comprise a mixture of probiotic microorganisms with excellent probiotic and other activities. Petition 870260037323, dated 04 / 22 / 2026, page 24 / 114 15 / 46 superior anti-allergic, anti-inflammatory, immunoregulatory and / or intestinal health improvement effects to further enhance its effects. Carriers that may be included in the food composition of the present invention may include, for example, extenders, high-fiber additives, encapsulating agents and lipids, which are widely known in the art. The Lactobacillus gasseri KBL697 strain in the present invention may be in lyophilized or encapsulated form or in the form of culture suspensions or dry powders.

[057] The composition of the present invention can also be provided in the form of a food additive comprising said strain or a food comprising the same.

[058] The food additive of the present invention may be in the form of a dry or liquid formulation and may also comprise other non-pathogenic microorganisms in addition to the Lactobacillus gasseri KBL697 strain. Microorganisms that can be added to feed additives may include, for example, Bacillus subtilis, which can produce protease, lipase, and sugar-converting enzymes; a strain of Lactobacillus, which has physiological activity and degradability of organic compounds under anaerobic conditions, such as in the stomach of a cow; filamentous fungi, such as Aspergillus oryzae, showing effects on increasing animal weight, milk production, and feed digestibility (Slyter, LLJ Animal Sci., 1976, 43, 910-926); and yeast, such as Saccharomyces cerevisiae (Johnson, DE et al. J. Anim. Sci., 1983, 56, 735-739; Williams, PEV et al., 1990, 211).

[059] The food additive of the present invention may further comprise at least one enzymatic agent in addition to said Lactobacillus gasseri KBL697 strain. The additional enzymatic agents may be in dry or liquid form and may include, for example, steatolytic enzymes such as lipase, phytase to produce phosphate and inositol phosphate by phytic acid degradation, amylase, i.e., an enzyme to hydrolyze the α-1,4-glycoside linkage included in, by Petition 870260037323, dated 04 / 22 / 2026, page 25 / 114 16 / 46 For example, starch and glycogen, phosphatase, that is, an enzyme to hydrolyze organic phosphoric acid ester, carboxymethylcellulase to degrade cellulose, xylase to degrade xylose, maltase to hydrolyze maltose into two glucose molecules, and sugar-producing enzymes such as invertase to produce the glucose-fructose mixture by hydrolyzing sucrose.

[060] In the use of the Lactobacillus gasseri KBL697 strain of the present invention as an additive for animal feed, feed raw materials such as peanuts, peas, beet, pulp, grain by-products, powdered animal tripe and powdered fishmeal, including various grains and soy protein, may be used. They may be processed or unprocessed and may be used without limitation. Processing may include, but is not limited to, a process in which the raw feed ingredients are loaded and compressed under pressure against a given outlet and, for proteins, extrusion by which the proteins are degenerated to increase availability may preferably be used. Extrusion denatures the proteins by means of heat treatment to destroy antienzymatic factors, which is advantageous.Furthermore, for soy proteins, their digestibility can be improved through extrusion to inactivate antinutrients, such as a trypsin inhibitor, one of the protease inhibitors present in soy. Additionally, extrusion can promote improved protease digestibility, increasing the nutritional value of soy proteins.

[061] According to another embodiment of the present invention, the present invention relates to an antifungal composition comprising at least one selection from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain.

[062] The composition can be characterized by showing antifungal activity against a selected group consisting of Malassezia furfur, Petition 870260037323, dated 04 / 22 / 2026, page 26 / 114 17 / 46 Malassezia globosa and Malassezia restricta, but not limited to these.

[063] The composition may be a composition to prevent, relieve or treat seborrheic dermatitis or dandruff, and said seborrheic dermatitis may be on the scalp.

[064] In addition, the said composition may be a composition to prevent, relieve or treat urticaria, pruritus, tinea corporis, tinea cruris, or tinea pedis, due to a fungal infection.

[065] The said strain and cultures of the said strain, lysates of the said strain and extracts of the said strain may comprise an amount of 0.1% by weight to 50% by weight, based on the total weight of the composition.

[066] The said antifungal composition may be a pharmaceutical composition, a cosmetic composition or a health food composition, and may also be an external skin preparation.

[067] The said cosmetic composition may be supplied in all dosage forms that are suitable for topical application, for example, in the form of a liquid, oil-in-water emulsion, water-in-oil emulsion, suspension, solid, gel, powder, paste, foam or aerosol. The said compositions of the above dosage forms may be prepared by conventional methods used in the art.

[068] In addition to the above ingredients, said composition may comprise other ingredients in an amount that does not impair the main effect, preferably in an amount to provide a synergistic effect on the main effect. The composition according to the present invention may comprise a substance selected from the group consisting of vitamins, polypeptides, polysaccharides and sphingolipids. Furthermore, the cosmetic composition of the present invention may comprise a moisturizer, an emollient, a surfactant, a UV absorber, a preservative, a sterilizer, an antioxidant, a pH adjusting agent, organic and inorganic pigments, a flavoring agent, an agent of Petition 870260037323, dated 04 / 22 / 2026, page 27 / 114 18 / 46 cooling agent or an antiperspirant. The percentage combination of said ingredients may be selected by those skilled in the art within a range that does not impair the purpose and effect of the present invention, and may be in a range of 0.01% by weight to 5% by weight and, specifically, from 0.01% by weight to 3% by weight, based on the total weight of the composition.

[069] According to the embodiment above, the antifungal composition of the present invention may be an external skin preparation, such as a cream, ointment, shampoo or treatment.

[070] According to another embodiment of the present invention, the present invention relates to a pharmaceutical composition for the treatment or prevention of allergic diseases, including atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases, comprising at least one selected from a group consisting of a cellular component of the Lactobacillus gasseri KBL697 strain, cultures of said strain, lysates of said strain and extracts of said strain.

[071] The pharmaceutical composition of the present invention may be provided in the form of a live bacterial cell component, dried strain, cultures of said strain, lysates of said strain, or a composition in combination with a pharmaceutically acceptable carrier or medium. Carriers or media that may be used herein may include a solvent, a dispersant, a coating, an enhancer, a controlled-release formulation (i.e., sustained-release formulation), or at least one inert excipient including starch, polyol, granules, microfine cellulose, microcrystalline cellulose, such as Celphere, Celphere spheres, diluent, lubricant, binder, disintegrant. The tablet of the preceding composition may, if desired, be coated by a standard aqueous or non-aqueous technique.Examples of pharmaceutically acceptable carriers and excipients for use as pharmaceutically acceptable inert carriers and said additional ingredients may include, for example, a binder, a filler, a disintegrant, a lubricant, an agent. Petition 870260037323, dated 04 / 22 / 2026, page 28 / 114 19 / 46 antimicrobial and a coating agent, but not limited to these.

[072] In addition, the pharmaceutical composition of the present invention can be used as an external preparation comprising a dosage form selected from the group consisting of ointments, creams, pastes, liquids and solutions for cutaneous application, glycerogelatins, liniments, powders for cutaneous application, aerosols and plasters.

[073] In the present invention, said allergic diseases refer to conditions associated with IL-4 or IL-5 expression and may include, for example, eczema, allergic asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria or anaphylaxis. Preferably, the present invention may be characterized in that the diseases are selected from the group consisting of infantile eczema, allergic asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis and food allergy, but not limited to these.

[074] The present invention can be characterized in that said intestinal diseases are selected from the group consisting of abdominal bloating, abdominal discomfort, infectious diarrhea caused by pathogenic microorganisms, gastrocolitis, inflammatory bowel diseases, neurogenic bowel syndrome, irritable bowel syndrome, small intestinal overgrowth of microorganisms and intestinal alimentary diarrhea, and the diseases also include those caused by damage to the intestinal barrier function.

[075] Inflammatory bowel disease (IBD) can include Crohn's disease, bowel lesions that accompany Behcet's disease, ulcerative colitis, bleeding rectal ulcer, and pouchitis, and refers to a group of diseases including Crohn's disease and ulcerative colitis. Ulcerative colitis affects only the large intestine. The inflammation and ulceration of ulcerative colitis are limited to the two innermost layers, mucosa and submucosa, of the four layers of the large intestine. The inflammation and ulceration of Crohn's disease can spread to all layers of the intestinal wall, both Petition 870260037323, dated 04 / 22 / 2026, page 29 / 114 20 / 46 in both the small and large intestines.

[076] Meanwhile, irritable bowel syndrome is a chronic condition that involves not only persistent and recurring abdominal discomfort, such as bloating, but also changes in bowel habits, such as diarrhea and constipation. Symptoms can be exacerbated by psychological factors or stressful social circumstances.

[077] In the present invention, inflammatory diseases collectively refer to conditions with inflammation as the primary lesion and may include, for example, edema, conjunctivitis, periodontitis, rhinitis, otitis media, chronic sinusitis, pharyngolaryngitis, tonsillitis, bronchitis, pneumonia, gastric ulcer, gastritis, colitis, gout, eczema, acne, atopic dermatitis, contact dermatitis, seborrheic dermatitis, ankylosing spondylitis, rheumatic fever, fibromyalgia, osteoarthritis, psoriatic arthritis, rheumatoid arthritis, periarthritis of the shoulder, tendinitis, tenosynovitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome, myasthenia gravis, sepsis, vasculitis, bursitis, temporal arteritis and multiple sclerosis, but are not limited to these.

[078] In the present invention, autoimmune diseases and symptoms that can be relieved by the immunoregulatory effect may include, for example, rheumatoid arthritis, lupus, systemic scleroderma, atopic dermatitis, psoriasis, psoriatic arthritis, asthma, Guillain-Barré syndrome, myasthenia gravis, dermatomyositis, polymyositis, multiple sclerosis, autoimmune encephalomyelitis, polyarteritis nodosa, Hashimoto's thyroiditis, multiple sclerosis, temporal arteritis, juvenile diabetes, alopecia areata, pemphigus, aphthous stomatitis, autoimmune hemolytic anemia, Wegener's granulomatosis, Sjögren's syndrome, Addison's disease, Crohn's disease and Behcet's disease, but are not limited to these.

[079] The present invention can be characterized in that the effects resulting from the strain of the present invention for immunoregulation, or for alleviating, treating or preventing autoimmune diseases or inflammatory diseases can be induced by at least Petition 870260037323, dated 04 / 22 / 2026, p. 30 / 114 21 / 46 a selected mechanism of increasing and decreasing cytokines associated with the inhibition of inflammation and immunoregulation, specifically decreasing the secretion of TNF-α, IFN-γ and IL-17 and increasing the secretion of IL-10.

[080] TNF-α (tumor necrosis factor-α) is a 17 kDa peptide produced by macrophages and several other activated cells during the host's immune response to bacterial infections and oncological diseases. This cytokine is also known as an important mediator of immune and inflammatory reactions and is also known as a pro-inflammatory cytokine that plays an important role in autoimmune and inflammatory diseases such as rheumatoid arthritis (RA), psoriatic arthritis, Crohn's disease, psoriasis, and ankylosing spondylitis (AS).

[081] On the other hand, CD4+ T cells can be classified into subtypes such as Th1 (T helper type 1), Th2 (T helper type 2), CD4+ CD25+ immunoregulatory T cells and Th17 (T helper 17 cell) depending on the expression of specific cytokines and transcription factors. Among them, IL-17 produced by Th17 cells is known to be most involved in autoimmune diseases, allergic reactions or in host defense against bacterial or fungal infections.

[082] In addition, IL-10 is a 35-40 kDa peptide produced by helper T cells, B cells, monocytes and other cells and has immunosuppressive and anti-inflammatory properties, for example, inhibition of cytokine production including TNF-α and IFN-γ.

[083] The term 'treat', unless otherwise stated, refers to reversing or alleviating diseases or conditions used with said term or one or more symptoms thereof, inhibiting their progression or preventing them. The term 'treatment', as used in the present invention, refers to an act of 'treating' as defined above. Consequently, the treatment or therapeutic regimen of a disease in mammals may include one or more of the following: (1) To inhibit the growth of the disease, that is, to inhibit its development. Petition 870260037323, dated 04 / 22 / 2026, p. 31 / 114 22 / 46 (2) Prevent the spread of the disease (3) Relieve the disease (4) Prevent recurrence of the disease and (5) Palliate the symptoms of the disease.

[084] A composition of the present invention for preventing or treating allergic diseases, such as atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases may comprise a pharmaceutically effective amount of the Lactobacillus gasseri KBL697 strain alone or in combination with at least one of pharmaceutically acceptable vehicles, excipients or diluents.

[085] In the present invention, the term “effective amount” means an amount that is high enough to provide a desired effect, but low enough to prevent serious side effects under medical evaluation. The amount of microorganisms administered to the body by the composition of the present invention can be appropriately adjusted in consideration of the route of administration and the target of administration.

[086] The composition of the present invention can be administered to a subject one or more times per day. Unit dosage means physically distinct units suitable for unit administration to human subjects and other mammals, and each unit comprises a suitable pharmaceutical carrier and a predetermined amount of the Lactobacillus gasseri KBL697 strain of the present invention to provide a therapeutic effect. The dosage unit for oral administration to an adult patient preferably contains 0.001 g or more of the microorganism of the present invention, and the oral dosage of the composition of the present invention is 0.001 g 10 g, and preferably 0.01 g 5 g per dose. The pharmaceutically effective amount of the microorganism of the present invention is 0.01 g 10 g / day. However, the dosage varies depending on the severity of the patient's disease and the effective microorganisms and auxiliary ingredients used in conjunction. Furthermore Petition 870260037323, dated 04 / 22 / 2026, p. 32 / 114 23 / 46 of this, the total daily dosage can be divided into several doses and administered continuously as needed. Consequently, the dosage ranges above do not limit the scope of the present invention in any way.

[087] Furthermore, the term “pharmaceutically acceptable”, as used above, refers to a composition that is physiologically acceptable and does not cause an allergic reaction, such as gastrointestinal upset, or dizziness, or a similar reaction when administered to a human being.

[088] A composition of the present invention can be formulated using methods known in the art so that rapid, sustained, or delayed release of the active ingredients, after administration to a mammal, can be provided. Dosage forms may be powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, or sterile powders. Furthermore, the composition of the present invention for preventing or treating allergic diseases, such as atopic dermatitis, inflammatory diseases, intestinal diseases, and / or autoimmune diseases, can be administered by various routes, including oral, transdermal, subcutaneous, intravenous, or intramuscular administration. The dosage of the active ingredients can be appropriately selected depending on various factors, such as the route of administration, the patient's age, sex, weight, and severity of the patient's condition.The composition of the present invention for the treatment of allergic diseases, such as atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases, can be administered in combination with a known compound having the effect of preventing, relieving or treating the relevant symptoms.

[089] The pharmaceutical composition of the present invention, in particular, can be provided in an oral unit dose form of an enteric-coated formulation. The term “enteric coating”, as used herein, comprises any known pharmaceutically acceptable coating that can Petition 870260037323, dated 04 / 22 / 2026, page 33 / 114 24 / 46 remain in the stomach without being degraded by gastric acid and can disintegrate sufficiently in the intestinal tract to release active ingredients therein. The “enteric coating” of the present invention refers to a coating that can be maintained for 2 hours or more when an artificial gastric juice, such as a pH 1 HCl solution, is contacted at 36°C to 38°C and subsequently can degrade, preferably in an artificial intestinal juice, such as a pH 6.8 KH2PO4 buffer solution in 30 minutes.

[090] The enteric coating of the present invention is coated onto a core in an amount of about 16 mg to 30 mg, preferably 16 mg to 20 mg or 25 mg or less. When the thickness of the enteric coating of the present invention is 5 μm to 100 μm, and preferably 20 μm to 80 μm, satisfactory results can be obtained as an enteric coating. The enteric coating material can be suitably selected from known polymeric materials. Suitable polymeric materials are listed in a number of known documents [L. Lachman et al., The Theory and Practice of Industrial Pharmacy, 3rd ed., 1986, pp. 365-373; H. Sucker et al., Pharmazeutische Technologie, Thieme, 1991, pp. 355-359; Hagers Handbuchder pharmazeutischen Praxis, 4th ed., Vol. 7, pp. 739 ~ 742 and 766 ~ 778, (SpringerVerlag, 1971); and Remington's Pharmaceutical Sciences, 13th ed., pp. 1689 ~ 1691 (Mack Publ., Co.[ , 1970)], and cellulose ester derivatives, cellulose ethers, an acrylic resin-methyl acrylate copolymer, and a maleic acid copolymer and phthalic acid derivatives may be included therein.

[091] The enteric coating of the present invention can be prepared using a conventional enteric coating method in which an enteric coating solution is sprayed onto a core. Suitable solvents used for the enteric coating process are alcohols, such as ethanol, ketones, such as acetone, halogenated hydrocarbon solvents, such as dichloromethane. Petition 870260037323, dated 04 / 22 / 2026, page 34 / 114 25 / 46 (CH2CI2), and mixed solvents of these solvents. A softener such as di-n-butyl phthalate or triacetin is added to the coating solution in a ratio of 1:approximately 0.05 to approximately 0.3 (coating material: softener). It is suitable to carry out the spraying process continuously, and the amount of spraying can be adjusted according to the coating conditions. The spray pressure can be adjusted in various ways, and satisfactory results can generally be obtained with a spray pressure of approximately 1 bar to approximately 1.5 bar.

[092] Meanwhile, the pharmaceutical composition of the present invention can be administered in combination with conventional drugs that are known to have a preventive or treatment effect on allergic diseases, inflammatory diseases, intestinal diseases and / or autoimmune diseases. For example, drugs that can be administered in combination with the pharmaceutical composition of the present invention may include antibody drugs used for the treatment of inflammatory diseases, intestinal diseases, or autoimmune diseases, such as infliximab, adalimumab, golimumab, abciximab, alemtuzumab, atlizumab, basiliximab, belimumab, bevacizumab, ipilimumab, brentuximab vecotin, canakinumab, capromab pendetide, catumaxumab, certolizumab pegol, cetuximab, daclizumab, denosumab, eculizumab, edrecolomab, efalizumab, efungumab, ertumaxomab, etanercept, etaracizumab, fontolizumab, gemtuzumab ozogamicin, girentuximab, ibritumomab tiuxetan, igovomab, Imchiromabe,movie, movie, movie, movie, movie, nofetumobe merpentana, movie, movie, movie, movie, movie, movie, movie, ranibizu rovelizumabe, ruplizumabe, tacatuzumabe tetraxetan, tefizumabe, tocilizumabe, tocilizumabe, trastuzumabe, ustequinumabe, secuquinumabe, vedolizumabe, vicilizumabe, votumumabe, Petition 870260037323, dated 4 / 22 / 2026, p. 35 / 114 26 / 46 zalutumumab and zanolimumabe, but not limited to these.

[093] In addition, the pharmaceutical composition of the present invention can be used in combination with antihistamines, steroids, salicylic acid, urea, tacrolimus, cyclophosphorine, phototherapy and the like, for the treatment of eczema and allergic diseases such as atopic dermatitis, and can be used in combination with sulfasalazine, azathioprine, mercaptopurine, methotrexate, cyclosporine, TNF blocking agents (adalimumab, etanercept, etc.) or integrin antibodies (vedolizumab, natalizumab, etc.), for the treatment of intestinal diseases such as inflammatory bowel diseases.

[094] In another embodiment of the present invention, the present invention provides the use of said strain or said composition to prevent or treat allergic diseases, such as atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases, and the use of said strain or said composition for the preparation of a therapeutic agent for the above diseases.

[095] Specifically, the present invention relates to a composition comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain, for use in the prevention or treatment of allergic diseases including atopic dermatitis, inflammatory diseases, intestinal diseases such as colitis, and / or autoimmune diseases such as psoriasis.

[096] The present invention also relates to the use of a composition for the preparation of a preventive or therapeutic drug for allergic diseases, including atopic dermatitis, inflammatory diseases, intestinal diseases such as colitis, and / or autoimmune diseases such as psoriasis, comprising at least one selected from the group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain.

[097] The term 'prevention', as used here, is associated with avoiding, delaying, preventing or hindering diseases from reducing them. Petition 870260037323, dated 04 / 22 / 2026, page 36 / 114 27 / 46

[098] The term 'treatment', as used here, is associated with caring for a person suffering from illness, in order to improve, cure or reduce the symptoms of the illness or to reduce or stop the progression of the illness.

[099] In another embodiment of the present invention, the present invention provides a method for preventing or treating allergic diseases, including atopic dermatitis, inflammatory diseases, intestinal diseases and / or autoimmune diseases, comprising administering a pharmaceutically effective amount of the strain or said composition to a subject in need of prevention or treatment of said diseases, or in need of relief of intestinal health, allergic reactions, inflammatory reactions or autoimmune reactions.

[0100] Specifically, the present invention provides a method for treating allergic diseases, including atopic dermatitis, inflammatory diseases, intestinal diseases such as colitis and / or autoimmune diseases such as psoriasis, comprising administering a therapeutically effective amount of at least one selected from a group consisting of said strain, cultures of said strain, lysates of said strain and extracts of said strain to a subject in need thereof.

[0101] Since the pharmaceutical composition used for the method to prevent or treat said diseases, and the method of administration thereof, have been described above, the overlapping contents between the composition and the method will be omitted here to avoid undue complexity in this descriptive report.

[0102] Meanwhile, the said subject to whom the composition for preventing or treating said diseases may be administered includes all animals, including humans. For example, the subject may be an animal, such as a dog, cat, or mouse.

[0103] In another embodiment of the present invention, the present invention relates to a cosmetic composition comprising an amount Petition 870260037323, dated 04 / 22 / 2026, page 37 / 114 28 / 46 pharmaceutically effective from at least one selected from the group consisting of the cellular component of the Lactobacillus gasseri KBL697 strain, cultures of said strain, lysates of said strain and extracts of said strain.

[0104] A cosmetic composition may be characterized by its function of relieving at least one sensitive skin condition selected from the group consisting of skin allergy, urticaria, atopic dermatitis, psoriasis, fungal infections and eczema, but not limited to these.

[0105] The term 'cosmetic composition', as used herein, refers to a composition comprising at least one selected from the group consisting of the cellular component of the Lactobacillus gasseri KBL697 strain, cultures of said strain, lysates of said strain and extracts of said strain, and may assume any type of dosage form. For example, cosmetics prepared using said cosmetic composition may include creams, packaging, lotions, essences, toners, foundations and makeup bases and may be marketed in any of the dosage forms listed above to achieve the objective of the present invention, but not limited to these. The ingredients comprised in the cosmetic composition of the present invention include those commonly used in cosmetic compositions, in addition to the above ingredients, for example, conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances and carriers.

[0106] In another embodiment of the present invention, the present invention relates to a functional adhesive comprising at least one selected from the group consisting of a cellular component of the Lactobacillus gasseri KBL697 strain, cultures of said strain, lysates of said strain and extracts of said strain, and said functional adhesive can be used for cosmetic or medical purposes.

[0107] The patch may be characterized by its function of relieving at least one sensitive skin condition selected from the group consisting of skin allergy, urticaria, atopic dermatitis, psoriasis, fungal infections and eczema, but not Petition 870260037323, dated 04 / 22 / 2026, p. 38 / 114 29 / 46 limited to these.

[0108] In the present invention, the patch is typically a small adhesive patch containing the substances to be administered, and the patch can assume a variety of forms. The simplest form is a single adhesive body comprising a reservoir containing the substances to be delivered placed on a support. The reservoir is typically formed of a cosmetically or pharmaceutically acceptable pressure-sensitive adhesive, but in some cases it can also be formed of non-adhesive materials provided with a thin adhesive layer suitable for the skin contact surface. The rate at which the substances to be delivered are administered from the patch to the subject using the patch can be altered because the permeability of the skin to the substances to be delivered generally depends on the individual and the location of the skin, which can be easily selected by those skilled in the art.

[0109] The present invention will now be described in more detail by means of examples. These examples are only for illustrative purposes of the present invention, and it will be evident to those skilled in the art that the scope of the present invention should not be interpreted as being limited by these examples. Example 1. Relief and Therapeutic Effects by KBL697 for Allergic Reactions Resulting from the Inhibition of Th2-Type Cytokines in T Cells

[0110] It has been reported that cytokines related to type 2 helper T cells (Th2), such as IL-4 and IL-5, contribute to chronic allergic reactions by increasing Th2-related immune responses and increasing IgE production (Passante E, Inflamm. Res. 2009). The present invention, by verifying the effect of inhibiting IL-4 and IL-5 secretion by various Lactobacillus strains, attempted to screen probiotic strains that can be used as therapeutic agents for various allergic diseases, including chronic allergic diseases. To this end, the effect of inhibiting the secretion of Petition 870260037323, dated 04 / 22 / 2026, page 39 / 114 30 / 46 IL-4 and IL-5 were tested as follows, using the EL4 cell line, which is a mouse T cell line. 1-1. Incubation of EL-4 Cell Lines

[0111] EL4 cells (ATCC No TIB-39) were cultured in DMEM medium supplemented with 10% FBS (fetal bovine serum), penicillin (100 μg / mL), and streptomycin (100 μg / mL) at 37°C under 5% CO2, and then subcultured once every three days. EL4 cells were seeded in a 24-well plate with a concentration of 4 χ 105 cells / well, then cultured for 16–20 hours to induce allergic reactions and treated with the strains. 1-2. Strain Incubation and Recovery

[0112] The Lactobacillus gasseri strains to be used were cultured in MRS medium supplemented with 0.5% cysteine, activated by means of a total of two subcultures at 18-hour intervals, and then used in experiments. The resulting culture solution was centrifuged at 15,000 χ²g for 3 minutes and the pellet was washed with PBS buffer. The strains were stained for 15 minutes with SYTO9 and PI using the LIVE / DEAD™ BacLight™ bacterial count and viability kit for flow cytometry (Thermo Fisher Scientific, USA). Then, the contained beads were added and the number of stained live bacteria was calculated using a flow cytometry assay. 1-3. Treatment of Strains and Measurement of IL-4 and IL-5 Secretion Amount after Inducing Allergic Reactions

[0113] To induce allergic reactions in EL4 cells previously seeded in a 24-well plate, each well was treated with 100 μL (20 ng / mL) of PMA and ionomycin (1 μg / mL). Then, 300 μL of the previously prepared strains were treated at a cell-to-strain ratio of 1:10. After incubation for 24 hours in a 5% CO2 incubator at 37°C, the supernatant was collected and the mouse IL-4 ELISA Set (Cat No. 555232, BD OptEIA™) and the IL-5 ELISA Set were analyzed. Petition 870260037323, dated 04 / 22 / 2026, page 40 / 114 31 / 46 mice (Cat No. 555236, BD OptEIA™) were used to measure the amount of IL-4 and IL-5 secreted, according to the manufacturer's method.

[0114] As a result, as shown in FIGS 1 and 2, it was confirmed that KBL697 effectively inhibited the secretion of IL-4 and IL-5, and the therapeutic and preventive effects of the same in allergies can be provided through the inhibition of the secretion of Th2-type cytokines that mediate an allergic reaction. Example 2. Relief and Treatment Effects of KBL697 for Allergic Reactions Resulting from Inhibition of Histamine Secretion in Basophils

[0115] It has been reported that, in an allergic reaction, histamine is expressed in tissues, causing an inflammatory reaction, and suppression of histamine secretion leads to relief of allergic symptoms by blocking the histamine reaction. In the present invention, the relief of allergic reactions and the therapeutic effect thereof through inhibition of histamine secretion by KBL697 have been further confirmed. In addition, in order to confirm whether the effect for the treatment and prevention of chronic allergies identified in Example 1 is an inherent attribute of Lactobacillus gasseri, or is a particularly notable effect in KBL697 among Lactobacillus gasseri, the ability to suppress histamine secretion was also evaluated for nine additional strains of Lactobacillus gasseri besides KBL697.After inducing degranulation following culture of the RBL-2H3 cell line, the ability to suppress histamine secretion was tested by measuring the activity of β-hexosaminidase co-secreted with histamine using a colorimetric reaction with a substrate. 2-1. Incubation of RBL-2H3 Cell Lines

[0116] RBL-2H3 (ATCC No. CRL-2256), the cells were cultured in DMEM medium supplemented with 10% FBS, penicillin (100 μg / mL) and streptomycin (100 μg / mL) at 37°C under 5% CO2, and then subcultured once every three days. RBL-2H3 cells were seeded in a 6-well plate at a concentration of 1 x 10⁶ cells / well, then cultured for 3 hours and then treated with Petition 870260037323, dated 04 / 22 / 2026, page 41 / 114 32 / 46 IgE (0.5 μg / mL) to incubate for 16 to 20 hours. 2-2. Incubation of Strains and Preparation of Culture Solution

[0117] The Lactobacillus gasseri strains to be used were cultured in MRS medium supplemented with 0.5% cysteine, activated by means of a total of two subcultures at 18-hour intervals, and then used in experiments. The resulting culture solution was centrifuged at 15,000 χ g for 3 minutes to collect the supernatant. 2-3. Induction of Degranulation after Strain Treatment

[0118] After removing the medium from RBL-2H3 cells that had been previously seeded in a 6-well plate, the cells were washed twice with 1 mL of Siraganian buffer (pH 7.2). Subsequently, the cells were treated with 120 μL of the previously prepared bacterial culture solution or ketotifen from the positive control group (20 μg / mL) per well, incubated for 20 minutes in a 5% CO2 incubator at 37 °C, followed by treatment with 60 μL of antigen (DNP-HAS, 1 μg / mL) to induce degranulation by antigen-antibody reaction. As a negative control, degranulation was induced after treatment with 120 μL of Siraganian buffer. The reaction was carried out in a 5% CO2 incubator at 37 °C for 20 minutes, and then the supernatant was collected. 2-4. Identifying the Color Reaction

[0119] To identify β-hexosaminidase activity, 25 μL of the supernatant collected in Example 2-3 were transferred to each well of a 96-well plate, and then 25 μL of substrate (p-nitrophenyl N-acetyl-D-glucosaminidase) was added to each, followed by a reaction at 37 °C in a 5% CO2 incubator for 90 minutes. Then, 200 mL of stopping solution (Na2CO3 / NaHCO3) was added to stop the reaction, and then the absorbance was measured at 405 nm. The absorbance when treated with each type of Lactobacillus gasseri was compared to the negative control group and converted to Petition 870260037323, dated 04 / 22 / 2026, page 42 / 114 33 / 46 percent to show the level of degranulation inhibition.

[0120] As a result, as can be seen in FIG. 3 and Table 1, KBL697 showed up to 4 times less β-hexosaminidase secretion compared to other Lactobacillus gasseri strains, which was confirmed to be lower than the commercially available antihistamine ketotifen, a positive control. As a result, KBL697 was found to exhibit excellent degranulation prevention activity to effectively relieve allergic symptoms caused by excessive histamine secretion. Table 1 Species Strain under Treatment or Treatment Drug β-hexosaminidase (fold change) - (Negative control) Siraganian Buffer 1.0 - (Positive control) Ketotifen 0.3861 Lactobacillus gasseri KBL697 0.2213 Lactobacillus gasseri KBL695 0.4601 Lactobacillus gasseri KBL698 0.4620 Lactobacillus gasseri KBL685 0.4450 Lactobacillus gasseri KBL686 0.4213 Lactobacillus gasseri KBL688 0.4571 Lactobacillus gasseri KBL373 0.5691 Lactobacillus gasseri SNUG50243 0.5309 Lactobacillus gasseri SNUG60080 1.0091 Lactobacillus gasseri SNUG60134 0.9236 Example 3. Analysis of Immunoregulatory and Inflammation-Inhibiting Effects of KBL697

[0121] The immunoregulatory and anti-inflammatory effects of KBL697 were also verified, in addition to its antiallergic efficacy. To this end, the relationship between IL-10, a representative cytokine with immunomodulatory function, and TNF-α and IL-6, which are the cytokines that are the main indicators of an inflammatory reaction (IL-W / TNF-α, IL-10 / IL-6), was measured using macrophages, which play a critical role in the inflammatory reaction. 3-1. Incubation of RAW264.7 Cell Lines

[0122] RAW264.7 cells (ATCC No TIB-71) were cultured in medium Petition 870260037323, dated 04 / 22 / 2026, page 43 / 114 34 / 46 DMEM supplemented with 10% FBS, penicillin (100 μg / mL), and streptomycin (100 μg / mL) was incubated at 37°C under 5% CO2, and then subcultured once every three days. The incubated RAW264.7 cells were seeded in a 24-well plate at a concentration of 1 χ¹⁰⁵ cells / well, then cultured for 16–20 hours and subsequently used for Example 3–3. 3-2. Strain Incubation and Sample Preparation

[0123] The culture solutions were corrected with the same number of live bacteria and then prepared as three samples: live bacteria, pasteurization, and heat death. The samples for live bacteria, pasteurization, and heat death were prepared according to the same method as Example 1-2. Then, the pasteurization sample was reacted at 70 °C for 30 minutes and prepared by the same centrifugation process. The heat death sample was sterilized at 121 °C for 15 minutes and prepared by the same process. As a negative control group, MRS medium supplemented with 0.5% cysteine ​​was used. 3-3. Treatment and Measurement of a Strain of Cytokine Amount Secreted After Induction of Inflammatory Reactions

[0124] To induce inflammatory reactions in RAW264.7 cells previously seeded in a 24-well plate, each well was treated with 500 μL of LPS (20 ng / mL). Then, 300 μL of the previously prepared strains were treated at a cell-to-strain ratio of 1:10 and incubated for 24 hours in a 5% CO2 incubator at 37 °C. The supernatant in the mixture of cultured cell strains was collected and mouse TNF ELISA Set II (Cat No. 558534, BD OptEIA™), mouse IL-6 ELISA Set (Cat No. 555240, BD OptEIA™) and mouse IL-10 ELISA Set (Cat No. 555252, BD OptEIA™) were used to measure an amount of each cytokine, according to the manufacturer's method.

[0125] As a result, as shown in FIG. 4, it was confirmed that KBL697, among the Lactobacillus gasseri strains, primarily induced secretion. Petition 870260037323, dated 04 / 22 / 2026, page 44 / 114 35 / 46 of IL-10 and therefore showed excellent effects in terms of immunoregulation and suppression of the inflammatory reaction. As shown in FIGS 5 and 6, from the ability to secrete IL-10 corrected with the pro-inflammatory cytokines TNF-α and IL-6, it was confirmed that the KBL697 treatment group showed the inhibitory effect on inflammation and the immunoregulatory capacity greatly improved compared to the control group. Consequently, it was found that KBL697 has immunoregulatory and inflammation-inhibiting activities through IL-10 secretion. Furthermore, these effects were similarly confirmed not only in live bacteria but also in pasteurized or heat-killed dead bodies (see Table 2 and Table 3), indicating that KBL697 can be used to suppress inflammatory reactions in various forms, such as dead bacteria. Table 2 IL-10 / TNF-a Live Heat-dead Pasteurized Control -2.4509342 (ND) -2.0474707 (ND) -1.9242497 (ND) KBL697 1.81114395 6.28130388 4.43515847 ND: Not Determined Table 3 IL-10 / 11-6 Live Heat-dead Pasteurized Control -6.010433 (ND) -4.6669667 (ND) -4.5960301 (ND) KBL697 2.4709538 8.1665268 5.65489003 ND: Not Determined Example 4. Analysis of the Antifungal Effects of KBL697

[0126] The antifungal effect of KBL697 was confirmed by a spot test method. Approximately 1% of KBL697 was inoculated into MRS liquid medium and then incubated in an incubator at 37°C for approximately 24 hours under conditions Petition 870260037323, dated 04 / 22 / 2026, p. 45 / 114 36 / 46 anaerobic conditions for stationary culture. The culture solution in which the cells were incubated was stained on MRS solid medium, which was prepared under anaerobic conditions, in a quantity of 10 μL at a time, and then incubated at 37 °C under anaerobic conditions for approximately 24 hours. KCTC 7545 of Malassezia furfur, a fungal microorganism, was prepared by inoculating it into mYPG liquid medium, which was prepared under aerobic conditions, at a rate of 1% and followed by incubation in an incubator at 37 °C for approximately 24 to 48 hours. The mYPG soft medium to be used for antifungal efficacy evaluation was prepared with the components shown in Table 4, and 2.5 mL of the prepared culture medium was inoculated with the culture solution in which 500 μL of M. furfur were incubated. 2.5 mL of mYPG medium inoculated with M. furfur was poured into MRS medium stained with KBL697 and dried for 1 hour. The dried medium was incubated under aerobic conditions in an incubator at 37 °C for 24 to 48 hours.When a clean zone was identified in the culture medium, antifungal activity was determined by measuring the length from the outside of the stained lactic acid bacteria to the clean zone. The clean zone is a part where fungal growth was inhibited, and the antifungal activity caused by lactic acid bacteria was determined along the length to the clean zone.

[0127] As a result of three repeated experiments, clean zones were identified at intervals of approximately 6.00 mm in the area stained with KBL697 (FIG. 7), indicating that KBL697 can effectively suppress the growth of fungal microorganisms. Table 4 Ingredients Proportion (g / l) Malt extract 5.0 Peptone 10.0 Glucose 20.0 Tween 40 1.0 Petition 870260037323, dated 04 / 22 / 2026, p. 46 / 114 37 / 46 Tween 80 1.0 Agar 4.5 Example 5. Effects of KBL697 in Relieving Atopic Conditions

[0128] In order to verify the effect on atopic relief among the allergy-enhancing effects of KBL697, the NC / Nga mouse model, an animal model of atopic skin disease, was used.

[0129] After dividing the NC / Nga mice into groups of five mice, the back of each mouse was shaved from the lower ear to the upper tail and the mice were left for 24 hours. Then, 200 μL of 1% DNCB (dinitrochlorobenzene) solution (acetone: olive oil = 3:1) was applied twice a week to the shaved area to induce atopic dermatitis. From the third week of dermatitis induction, 200 μL of PBS was administered orally to the mice in the control group daily; The cultured KBL697 strain was centrifuged, washed by dilution with PBS and recovered, and then prepared so that at least 2 χ¹⁰⁹(KBL697-9) / 2 χ¹⁰⁸(KBL697-8) / 2 χ¹⁰⁷(KBL697-7) CFU could be added to 200 μL of PBS, which was administered orally to mice in the test group at 200 pL / day. Meanwhile, 200 pL of dexamethasone (60 pg / mL) were administered to mice in the positive control group.So, during three weeks of bacterial administration, the dermatitis scores of the mice in the control and test groups were measured weekly, and in the 3rd week after bacterial administration, the mouse's scratching time and skin thickness, and the concentration of IgE in the blood after performing autopsies on the mice, were measured. 5-1. Dermatitis Score Assessment

[0130] To assess DNCB-induced skin lesions, the dermatitis score was measured using the following method. Skin conditions were Petition 870260037323, dated 04 / 22 / 2026, page 47 / 114 38 / 46 monitored subjects were photographed for 3 weeks at one-week intervals starting from the 3rd week after strain administration. Four indicators of dryness, edema, erythema / hemorrhage, and skin erosion / excoriation were checked. A condition without lesions was scored as point 0, a mild condition as point 1, a moderate condition as point 2, and a severe condition as point 3, and the total score was evaluated.

[0131] As a result, as shown in FIG. 8, the DNCB-induced dermatitis score was significantly reduced in the group dosed with KBL697, compared to the control (negative) group where atopic dermatitis was induced and, in particular, the test group (KBL697-9) in which KBL697 was administered at 2 χ 109CFU showed an even lower dermatitis score than the positive control group of dexamethasone administration. As a result, the effect of treating atopic dermatitis according to the administration of KBL697 was verified. 5-2 Itch Relief Effects

[0132] In order to verify the itch-relieving effect of KBL697 administration in mouse models suffering from DNCB-induced atopic dermatitis, scratching time was measured by video recording of the mouse models for 10 minutes after 3 weeks of strain administration.

[0133] As a result, as can be seen in FIG. 9, it appeared that the scratching time was significantly reduced in all test groups in which KBL697 was administered, compared with the PBS administration group, which confirmed that the itching symptoms of atopic dermatitis were greatly relieved by the administration of KBL697. 5-3. Reduction in Skin Thickness

[0134] In order to verify the itching-relieving effect after administration of KBL697 to mouse models suffering from atopic dermatitis induced by Petition 870260037323, dated 04 / 22 / 2026, p. 48 / 114 39 / 46 DNCB, mouse ear thickness and dorsal skin thickness were measured with calipers three weeks after strain administration, and symptom relief of edema due to atopic dermatitis was observed.

[0135] As a result, as can be seen in FIGS 10 and 11, it was observed that in the test group dosed with KBL697 and in the positive control group, the ear and dorsal skin thickness were significantly reduced. 5-4. Decreased IgE Concentration in the Blood

[0136] It has been found that IgE concentration in patients with atopic dermatitis increases primarily with increasing clinical severity of atopic dermatitis (Matsumoto M, J. Immunol. 1999). Thus, IgE concentration, a representative hematological factor that appears when atopic dermatitis arises, was measured by collecting blood three weeks after the strain was administered, separating the serum from it and using the Mouse IgE ELISA Set (Cat No 555248, BD OptEIA™).

[0137] As a result, as shown in FIG. 12, it was found that the concentration of IgE in the blood decreased significantly in the test group in which KBL697 was administered orally, which indicated the antiallergic effect after the administration of KBL697. Example 6. Effects of KBL697 on Strengthening the Mesenteric Tight Junction

[0138] In the case of patients with colitis, the expression of proteins involved in the tight junction of enterocytes decreases, resulting in greater cell permeability, which leads to more severe inflammatory reactions (J. Landy, World J. Gastroenterol., 2016). In this regard, the present invention attempted to confirm whether KBL697 could increase the tight junction in Caco-2 cell lines, a representative intestinal epithelial cell model. 6-1. Incubation of Caco-2 Cell Lines Petition 870260037323, dated 04 / 22 / 2026, page 49 / 114 40 / 46

[0139] Caco-2 cells (ATCC No HTB-37) were incubated in MEM medium supplemented with 10% FBS, penicillin (100 μg / mL) and streptomycin (100 μg / mL) at 37 °C under 5% CO2, replacing the medium once every 2 days, and then subcultured once every 4 days. 6-2. Tight Joint Measurement

[0140] 200 μL of Caco-2 cells were seeded in the top layer of a 24 Transwell plate (Corning, USA) at a concentration of 3 χ¹⁰⁵ cells / mL and then incubated for seven days. The following day, after replacing the medium with one containing only MEM without FBS, the cells were incubated overnight, and a rod electrode array was inserted to measure TEER (transepithelial electrical resistance) using an EVOM Epithelial Tissue Voltohmmeter (World Precision Instruments, Florida, USA) (0h TEER). The strains were then treated so that the cell-to-strain ratio was 1:100 and incubated for 24 hours, at which point the TEER was measured (24h TEER).

[0141] After calculating using the equation: TEER ^cm2)= (resistance (Ω) - background resistance (Ω)) x membrane area (cm2), the following equation applied: Change in TEER (%) = 24h TEER ^cm2) / 0h TEER ^cm2) x 100

[0142] As a result, as shown in FIG. 13, Caco-2 cell lines treated with KBL697 showed that the tight junction increased by 20%, compared to the control group, indicating that KBL697 has an effect of restoring weakened intercellular junctions between enterocytes due to colitis. On the other hand, such an effect was not found in the other strains KBL342 and KBL381 of Lactobacillus gasseri. Example 7. Effects of KBL697 in the Treatment and Prevention of Colitis

[0143] In order to verify the therapeutic effect of KBL697 in colitis, mouse models in which colitis was induced were used. The models of Petition 870260037323, dated 04 / 22 / 2026, p. 50 / 114 41 / 46 mice were divided into groups of five C57BL / 6 mice and then fed tap water with 3% DSS dissolved in it for 5 days, thus inducing colitis. Subsequently, the mice in the positive control group were orally administered the steroid-based drug prednisolone in 200 μL of PBS at a dose of 1 mg / kg / day, and the mice in the test group were provided daily via oral administration with 200 μL of KBL697 strains that were prepared in the same manner as in Example 5 and then each diluted to be 5 χ 109 CFU / mL, 5 χ 108 CFU / mL, and 5 χ 107 CFU / mL. The control mice were orally administered 200 μL of PBS daily.The PBS used in this example was prepared so that 0.05% cysteine ​​could be added to rule out the effect of small amounts of cysteine ​​that was included in the strain culture solution composition and remained even after washing, in accordance with the report that cysteine ​​was associated with anti-inflammation in some cells (Hasegawa, S et al., Clin Exp Immunol. 2012, 167, 269-27). From the day the DSS began to be consumed until day 21, weight changes in mice in the control and test groups were measured daily, and on day 21 after the DSS was provided, the mice underwent autopsies to measure colon length.

[0144] As a result, as shown in FIG. 14, it was found that in mice with induced colitis dosed with 1 χ¹⁰⁹ CFU of KBL697, similarly to mice in the control group, body weight decreased rapidly until day 10, and then gradually recovered to restore normal levels by day 21. In particular, as shown in FIG. 15, in mice administered orally with 1 χ¹⁰⁹ CFU of KBL697 (KBL697 χ¹⁰⁹), colon length was found to have recovered to 90% of the Naive group level, and the symptom of reduced colon length was significantly alleviated compared to the negative control group of less than 80%. As a result, Petition 870260037323, dated 04 / 22 / 2026, p. 51 / 114 42 / 46 It was found that KBL697 showed an improvement effect on colitis disease. Example 8. Effects of KBL697 in the Treatment and Prevention of Psoriasis

[0145] In order to verify the effects of KBL697 in relieving psoriasis, Balb / c mouse models were used.

[0146] After dividing the Balb / c mice into groups of five mice, the control group mice were orally administered 200 μL of PBS daily for ten days, while the test group mice were orally administered 200 μL of each test strain diluted in PBS at least 1 χ¹⁰⁹ CFU / 0.2 mL per day. The strains and the control group were prepared in the same manner as in Example 7. Two weeks after bacterial administration, the back of each mouse was shaved from the lower end of the ear to the middle of the back, and the mice were left for 24 hours. Then, 62.5 mg of 5% imiquimod cream was applied to the shaved area once daily, causing psoriasis. Following the induction of psoriasis, mice in the positive control group received 200 μL of dexamethasone (0.25 mg / mL) daily. The same amount of KBL697 was administered daily even while psoriasis was being induced.For ten days after psoriasis was induced, the area of ​​psoriasis and the severity index (PASI) of mice in the control and test groups were measured at two-day intervals, and on the 10th day after psoriasis was induced, the skin thickness of each mouse was measured and then the mouse was subjected to autopsy to determine the concentration of cytokines in skin tissues and blood. 8-1. PASI Measurement and Changes in Skin Thickness

[0147] To assess imiquimod-induced cutaneous psoriasis lesions, the PASI score was measured using the following method. Three indicators of erythema, scaling, and skin thickness were checked. A lesion-free condition was scored as 0, a mild condition as 1, and a moderate condition as 2. Petition 870260037323, dated 04 / 22 / 2026, p. 52 / 114 43 / 46 as point 2, a serious condition as point 3, and a very serious condition as point 4, and the total score was evaluated.

[0148] As a result, as shown in FIG. 16 (A), PASI was significantly reduced in the imiquimod-induced psoriasis group administered with KBL697 similarly to the positive control group administered with dexamethasone (DXM), compared to the control group (NC) where psoriasis was induced. Furthermore, as a result of measuring ear and dorsal skin thickness in mice using calipers and observing the effect on relieving the symptom of edema due to psoriasis, as shown in FIG. 16 (B), it was found that ear and dorsal skin thicknesses were significantly reduced in the test group dosed with KBL697, similarly to the positive control group. 8-2. Cytokine Measurement

[0149] In the case of psoriasis, it is known that Th1 cytokine reactions, such as IFNγ and TNF-α, as well as Th17 responses, representatively IL-17, play an important role in the development and exacerbation of symptoms (Brembilla NC, Front Immunol. 2018). Mice with imiquimod-induced psoriasis underwent autopsies to determine cytokine concentrations in skin tissues and blood. Cytokine concentration was determined with protein samples taken from skin tissues and serum samples prepared from blood in the same manner as in Example 5-4 using each of the following mouse TNFα ELISA Set kits (Cat No. 555138, BD OptEIA™), mouse IFN-γ ELISA Set kits (Cat No. 558534, BD OptEIA™), mouse IgE ELISA Set kits (Cat No. 555248, BD OptEIA™), and mouse IL-17 DuoSet ELISA kits (Cat No. DY42105, R&D SYSTEMS).

[0150] As can be seen in FIG. 17, it has been confirmed that inflammatory cytokines such as TNF-α and IFN-γ in cutaneous tissues are increased in Petition 870260037323, dated 04 / 22 / 2026, p. 53 / 114 44 / 46 mice induced with psoriasis were reduced by KBL697. Furthermore, it was confirmed that Th17-specific IL-17 was also increased in psoriasis-induced skin and serum tissues, but decreased by KBL697 administration. As a result, it was found that KBL697 administration could reduce inflammatory cytokines that specifically increase at the onset of psoriasis, exhibiting effects in the treatment or prevention of the disease through a reduction effect. Example 9. Effects on the Treatment and Prevention of Colitis after Simultaneous Administration of an Antibody to Treat Colitis and KBL697

[0151] Infliximab (product name Remicade) is a recombinant antibody therapeutic drug used as an injection for autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, Crohn's disease in adults, Crohn's disease in children, psoriasis, and psoriatic arthritis. The aim of this study was to confirm the effect of improving intestinal disease symptoms in vivo in the case of simultaneous administration of KBL697 and infliximab.

[0152] After dividing the C57BL / 6 mice into groups of eight mice, the mice were fed tap water with 2% DSS dissolved in it for 8 days (D0 to D7), inducing colitis. At the same time, 200 μL of PBS were administered orally to the mice in the control group for 14 days (D0 to D13) daily, while 200 μL of the KBL697 strain diluted in PBS to 1 x 1010 CFU / mL were administered orally to the mice in the KBL697-dosed group so that the daily administration amount could be fixed at 2 χ 109 CFU. In the therapeutic antibody administration group, the antibody infliximab was administered once every 3 days at a dose of 5 mg / kg per mouse, and 200 μL of PBS was administered orally daily during the period in which the KBL697 strain was administered. In the test group for simultaneous administration, 200 μL of the KBL697 strain solution diluted in Petition 870260037323, dated 04 / 22 / 2026, p. 54 / 114 45 / 46 PBS at a concentration of 1 χ²¹⁰ CFU / ml was administered orally daily, and on the third day, the antibody infliximab was injected intravenously at a dose of 5 mg / kg per mouse. Test groups without infliximab antibody administration were injected intravenously with the same volume of PBS. During the 14 days that colitis was induced by DSS, changes in body weight of mice in the control group and each test group were measured daily, and on the 14th day after DSS was administered (D14), mice underwent autopsies to measure colon length.

[0153] As a result, as shown in Fig. 18 (A), regarding the change in colon length, the extent of the decrease in colon length was significantly improved in the groups in which KBL697 was administered alone (DSS + KBL697) and in those in which infliximab was administered alone (DSS + IFX), compared with the control group mice (DSS + PBS). In the group in which infliximab and KBL697 were administered simultaneously (DSS + Combine), it was confirmed that there was a significant improvement in colon length compared with the group in which infliximab or KBL697 were administered alone.

[0154] Regarding the change in body weights, as shown in Fig. 18 (B), when 14 days had elapsed after administration, the effect on body weight reduction was significantly improved in the groups that received KBL697 alone (DSS + KBL697) and in those that received infliximab alone (DSS + IFX), compared to the untreated control group mice. Three days after administration, it was confirmed that the elevated body weights were maintained in the group in which infliximab and KBL697 were administered simultaneously (DSS + Combination), compared to all test groups in which DSS was administered, verifying the symptom-relieving effect of body weight reduction due to colitis induction. Consequently, regarding the use of Petition 870260037323, dated 04 / 22 / 2026, page 55 / 114 46 / 46 said strain for the treatment of irritable bowel syndrome, it was confirmed that a stronger therapeutic effect could be expected when the strain was administered in combination with commercially available therapeutic antibodies.

[0155] The specific aspects of the present invention have been described in detail above, and it is obvious to those skilled in the art that these specific aspects are only preferred embodiments, and the scope of the present invention is not limited by them. Therefore, the scope of the present invention is substantially defined by the following claims, with equivalents to the claims.

[0156] Name of the Depositary Organization: Korea Research Institute of Bioscience & Biotechnology

[0157] Access Number: KCTC13520BP

[0158] Access Date: 20180427 Industrial Applicability

[0159] The Lactobacillus gasseri KBL697 strain (Accessory No. KCTC 13520BP), according to the present invention, attenuates allergic cell reactions, significantly improves the symptoms of atopic dermatitis, and exhibits anti-inflammatory, immunoregulatory, and antifungal effects, as well as a therapeutic effect on intestinal diseases such as irritable bowel syndrome and colitis. Thus, the single strain alone can achieve all the purposes of alleviating allergic and inflammatory diseases, improving intestinal health and immunoregulation, thus finding advantageous applications as a probiotic substance. Furthermore, the strain, based on its antifungal activity, can be advantageously used in an external skin preparation against various skin diseases caused by fungi and in a cosmetic composition and a functional plaster for the relief of sensitive skin. Free Text from Sequence Listing

[0160] An electronic file of the Sequence Listing attached Petition 870260037323, dated 04 / 22 / 2026, p. 56 / 114

Claims

1 / 2 CLAIMS 1. Pharmaceutical composition for the treatment or prevention of allergic diseases, inflammatory diseases, intestinal diseases or autoimmune diseases, CHARACTERIZED in that it comprises at least one selected from the group consisting of a strain of Lactobacillus gasseri KBL697 with Accession No. KCTC 13520BP, and lysates of said strain, and being presented in an enteric-coated dosage form.

2. Use of a composition CHARACTERIZED by the fact that it is for the preparation of a preventive or therapeutic drug for allergic diseases, inflammatory diseases, intestinal diseases or autoimmune diseases, wherein the composition comprises at least one selected from the group consisting of a strain of Lactobacillus gasseri KBL697 with Accession No. KCTC 13520BP, and lysates of said strain, and wherein the autoimmune diseases are selected from the group consisting of psoriasis and psoriatic arthritis.

3. Use according to claim 2, CHARACTERIZED in that said allergic diseases are selected from the group consisting of eczema, allergic asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis and food allergies.

4. Use, according to claim 2, CHARACTERIZED in that said inflammatory diseases are selected from the group consisting of edema, conjunctivitis, periodontitis, rhinitis, otitis media, chronic sinusitis, pharyngolaryngitis, tonsillitis, bronchitis, pneumonia, gastric ulcer, gastritis, colitis, gout, eczema, acne, atopic dermatitis, contact dermatitis, seborrheic dermatitis, ankylosing spondylitis, rheumatic fever, fibromyalgia, osteoarthritis, psoriatic arthritis, rheumatoid arthritis, periarthritis of the shoulder, tendinitis, tenosynovitis, myositis, hepatitis, cystitis, nephritis, Sjögren's syndrome, myasthenia gravis, sepsis, vasculitis, bursitis, temporal arteritis and multiple sclerosis.

5. Use, according to claim 2, CHARACTERIZED by the fact that said intestinal diseases are selected from the group consisting of abdominal bloating, abdominal discomfort, infectious diarrhea caused by pathogenic microorganisms, gastrocolitis, inflammatory bowel diseases, neurogenic bowel syndrome, irritable bowel syndrome, small intestinal overgrowth, and alimentary diarrhea.

6. Use, in accordance with claim 2, CHARACTERIZING the fact that said composition is used in combination with at least one drug selected from the group consisting of infliximabe, adalimumabe, golimumabe, abciximabe, alemtuzumabe, atlizumabe, basiliximabe, . belimumabe, bevacizumabe, ipilimumabe, brentuximabe vecotina, canaquinumabe, capromabe pendetida, catumaxomabe, certolizumabe pegol, cetuximabe, daclizumabe, denosumabe, eculizumabe, edrecolomabe, efalizumabe, efungumabe, ertumaxomabe, etanercept, etaracizumabe, fontolizumabe, gemtuzumabe ozogamicina, girentuximabe, ibritumomabe five, igovomabe, imciromabe, ipilimumabe, labetuzumabe, mepolizumabe, motavizumabe, natalizumabe, nimotuzumabe, nofetumomabe merpentana, ofatumumabe, omalizumabe, oregovomabe, palivizumabe, panitumumabe, pemtumomabe, pertuzumabe, ranibizumabe, raxibacumabe, rituximabe, rovelizumabe, ruplizumabe, tacatuzumabe tetraxetana, tefibazumabe, tocilizumabe, tositumomabe, trastuzumabe,ustekinumab, secukinumab, vedolizumab, visilizumab, votumumab, zalutumumab, and zanolimumab. Petition 870260081432, dated 08 / 13 / 2026, pp. 9 / 11.

Images