Novel lactobacillus fermentum hem20792 strain, and composition comprising strain or culture thereof for preventing or treating chronic obstructive pulmonary disease (COPD)

Abstract

The present invention relates to a novel Lactobacillus fermentum HEM20792 strain, a composition comprising the strain or a culture thereof for preventing or treating chronic obstructive pulmonary disease (COPD), and the like. The composition comprising a Lactobacillus fermentum HEM20792 strain (KCTC14066BP) as an active ingredient, according to the present invention, inhibits lung tissue damage and suppresses immune cells, and thus can prevent or treat COPD including emphysema. Therefore, it is expected that the present invention can be used to help cure pulmonary disease by eliminating a fundamental cause of COPD.

Description

A novel Lactobacillus fermentum HEM20792 strain, and a composition for the prevention or treatment of chronic obstructive pulmonary disease (COPD) comprising said strain or a culture thereof

[0001] The present invention relates to a novel Lactobacillus fermentum HEM20792 strain, and a composition for the prevention or treatment of chronic obstructive pulmonary disease (COPD) comprising said strain or a culture thereof.

[0002] The present application claims priority based on Korean Patent Application No. 10-2024-0170940 filed on November 26, 2024, and all contents disclosed in the specification and drawings of said application are incorporated into the present application.

[0003] Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease that causes shortness of breath by inducing persistent inflammation in the airways and lungs. COPD includes conditions such as emphysema and chronic bronchitis, and symptoms such as coughing, phlegm, and shortness of breath appear and tend to gradually worsen over time.

[0004] While both chronic obstructive pulmonary disease (COPD) and asthma are respiratory diseases, there are several important differences. Regarding causes, COPD is primarily caused by long-term exposure to irritants such as smoking, air pollution, and occupational dust (organic, inorganic, chemical, gas, or soot), and is mainly driven by environmental factors. In contrast, asthma is primarily caused by allergic reactions or specific irritants (dust, pollen, animal dander, etc.), and genetic factors also play a role. Regarding the timing of onset, COPD typically develops after middle age, with symptoms appearing gradually and worsening over time, whereas asthma can develop from childhood regardless of age, with symptoms appearing intermittently and potentially worsening in attacks.

[0005] The pathophysiological mechanisms of chronic obstructive pulmonary disease (COPD) include chronic inflammation of the airways, alveolar destruction, and airflow limitation. In the case of chronic inflammation of the airways, harmful substances such as smoking cause inflammation, leading to increased mucus secretion and narrowing of the airways. In the case of alveolar destruction, lung elasticity decreases, and gas exchange capacity is impaired. In the case of airflow limitation, the narrowing of the airways due to inflammation and alveolar destruction restricts airflow.

[0006] Current treatments for chronic obstructive pulmonary disease (COPD) include inhalers, oral medications, and oxygen therapy, which primarily aim to alleviate symptoms and slow disease progression. However, these treatments fail to eliminate the underlying causes of the disease, and despite long-term treatment, many patients continue to face severe deterioration in quality of life and premature death. Therefore, there is a pressing need for new approaches to the prevention and treatment of COPD.

[0007] Probiotics are well known as microorganisms that have beneficial effects on health by regulating the balance of gut microbes. Probiotics include lactic acid bacteria and bifidobacteria, and they play an important role primarily in promoting digestive health and strengthening the immune system.

[0008] In particular, Lactobacillus is a representative lactic acid bacterium that plays an important role in promoting digestive health and strengthening the immune system. Specifically, it helps improve digestive health by inhibiting the growth of harmful microorganisms, increasing resistance to certain viruses, promoting the growth of beneficial bacteria, and improving the intestinal environment.

[0009] Accordingly, the present invention proposes a novel Lactobacillus fermentum HEM20792 strain and a use therein for the prevention or treatment of chronic obstructive pulmonary disease.

[0010] The inventors conducted experiments to confirm the lung function-improving effects of the HEM20792 strain using an emphysema mouse model. As a result, it was confirmed that the HEM20792 strain is effective in preventing or treating chronic obstructive pulmonary disease, such as by inhibiting lung tissue damage and inducing a reduction in immune cells. Accordingly, the invention was completed based on the above effects of the HEM20792 strain.

[0011] The objective of the present invention is to provide pharmaceutical compositions, food compositions, and quasi-drug compositions, etc., containing the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) or a culture thereof as an active ingredient based on the effect of the said strain, thereby preventing, improving, and treating chronic obstructive pulmonary disease by eliminating the underlying cause of said disease.

[0012] However, the technical problems that the present invention aims to solve are not limited to those mentioned above, and other unmentioned problems will be clearly understood by those skilled in the art to which the present invention belongs from the description below.

[0013] The terms used in this specification are for illustrative purposes only and should not be interpreted as being limiting. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this specification, terms such as "comprising" or "having" are intended to indicate the existence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0014] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by those skilled in the art to which the embodiments pertain. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an ideal or overly formal sense unless explicitly defined in this application.

[0015] The present invention will be described in more detail below.

[0016] The present invention provides a pharmaceutical composition for the prevention or treatment of chronic obstructive pulmonary disease (COPD), comprising the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) or a culture thereof as an active ingredient.

[0017] In the present invention, "chronic obstructive pulmonary disease (COPD)" refers to a respiratory disease characterized by an abnormal inflammatory response of the lungs caused by the inhalation of harmful particles (such as tobacco) or gases, accompanied by airflow limitation that is not completely reversible and progressive. According to one embodiment of the present invention, chronic obstructive pulmonary disease may be emphysema or chronic bronchitis, but is not limited thereto.

[0018] In the present invention, the "Lactobacillus fermentum" is a Gram-positive bacterium and is one of the bacteria belonging to the genus Lactobacillus. This strain mainly inhabits various parts of the body, such as the intestines, oral cavity, and vagina of humans and animals, and can also be found in fermented foods.

[0019] In the present invention, "emphysema" is a disease in which respiratory distress occurs due to a decrease in the lungs' oxygen-carbon dioxide exchange capacity, resulting from damage to the alveoli in the peripheral airways and the abnormal, permanent expansion of the walls of the interalveolar spaces in the terminal bronchioles due to loss of elasticity and destruction. Emphysema progresses as an inflammatory response is activated by the induction of secretion of various cytokines and chemokines from macrophages and epithelium within the alveoli caused by factors such as smoking.

[0020] In the present invention, the "Chronic Bronchitis" is a disease in which the bronchi are in a state of continuous inflammation due to long-term exposure to harmful substances such as tobacco. Clinically, it can be diagnosed if there is coughing and phlegm for at least 3 months per year for more than 2 consecutive years.

[0021] In the present invention, the strain can inhibit damage to lung tissue, and said damage may be caused by smoking or secondhand smoke, but is not limited thereto. Additionally, said strain may have a function for treating, improving, alleviating, or preventing chronic obstructive pulmonary disease, but is not limited thereto.

[0022] In the present invention, the composition may comprise the Lactobacillus fermentum HEM20792 strain, the live cells thereof, the dead cells thereof, the culture medium thereof, the lysate thereof and / or the extract thereof.

[0023] In the present invention, the term "dead cell" refers to a form in which the growth of bacteria is prevented by heat treatment or the like, as opposed to live bacteria, by means of live bacteria and metabolites obtained through fermentation. The dead cell may include cytoplasm, a cell wall, antimicrobial active substances such as bacteriocin, polysaccharides, organic acids, etc. Products utilizing the dead cell possess high stability compared to live bacterial products; in particular, they exhibit excellent heat resistance and high stability against external environments, offering the advantages of easier storage and extended shelf life compared to existing live bacterial products. Furthermore, due to the tightening of regulations on antibiotic use, there is significant potential for marketability and growth, as the number of companies that have fully entered the production of dead cell products is still very small.

[0024] In the present invention, the term "culture solution" refers to a product obtained by culturing the strain of the present invention in a known liquid medium or solid medium, and may be used interchangeably with "culture product."

[0025] In the present invention, the strain may suppress immune cells and may suppress the expression of cytokines or chemokines, but is not limited thereto. Specifically, it may reduce one or more selected from the group consisting of lymphocytes, neutrophils, macrophages, and CD8+IL-17+IFNr-, but is not limited thereto.

[0026] In the present invention, "CD8+IL-17+IFNr-" represents a specific type of T cell subset. Here, CD8+ refers to CD8-positive T cells, IL-17+ refers to IL-17-positive cells, and IFN-γ refers to IFN-γ-negative cells. This type of T cell is a cell that produces IL-17 but does not produce IFN-γ. IL-17 is primarily involved in promoting inflammation, while IFN-γ plays various roles in immune responses.

[0027] In the present invention, the pharmaceutical composition according to the present invention may further comprise a suitable carrier, excipient, and diluent commonly used in the manufacture of pharmaceutical compositions. The excipient may be one or more selected from the group consisting of, for example, diluents, binders, disintegrants, lubricants, adsorbents, humectants, film-coating materials, and controlled-release additives.

[0028] The pharmaceutical composition according to the present invention may be formulated and used in the form of external preparations such as powders, granules, sustained-release granules, enteric granules, liquids, eye drops, ellipsoids, emulsions, suspensions, ethanol tablets, troches, fragrances, limonades, tablets, sustained-release tablets, enteric tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, irrigation solutions, warning agents, lotions, pastes, sprays, inhalants, patches, sterile injectable solutions, or aerosols, according to conventional methods, and the external preparations may have formulations such as creams, gels, patches, sprays, ointments, warning agents, lotions, liniments, pastes, or cataplasms.

[0029] Carriers, excipients, and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0030] In the present invention, when formulating a composition, it may be prepared using a diluent or excipient such as a commonly used filler, extender, binder, wetting agent, disintegrant, or surfactant, but is not limited thereto.

[0031] Excipients such as corn starch, potato starch, wheat starch, lactose, sucrose, glucose, fructose, D-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, calcium monohydrogen phosphate, calcium sulfate, sodium chloride, sodium bicarbonate, refined lanolin, microcrystalline cellulose, dextrin, sodium alginate, methylcellulose, sodium carboxymethylcellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropylmethylcellulose (HPMC) 1928, HPMC 2208, HPMC 2906, HPMC 2910, propylene glycol, casein, calcium lactate, primogel, etc., as additives to tablets, powders, granules, capsules, pills, and lozenges according to the present invention; Gelatin, gum arabic, ethanol, agar powder, cellulose phthalate, carboxymethylcellulose, calcium carboxymethylcellulose, glucose, purified water, sodium casein, glycerin, stearic acid, sodium carboxymethylcellulose, sodium methylcellulose, methylcellulose, microcrystalline cellulose, dextrin, hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, refined shellac, starch paste, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, etc. may be used as binders, and hydroxypropylmethylcellulose, corn starch, agar powder, methylcellulose, bentonite, hydroxypropyl starch, sodium carboxymethylcellulose, sodium alginate, Calcium carboxymethylcellulose, calcium citrate, sodium lauryl sulfate, anhydrous silica, 1-hydroxypropylcellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, sodium bicarbonate, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, amylopectin, pectin, sodium polyphosphate, ethylcellulose, sucrose, magnesium aluminum silicate, D-sorbitol solution, hard anhydrous silica, etc. disintegrants;Lubricants such as calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopodium pods, kaolin, petroleum jelly, sodium stearate, cocoa paste, sodium salicylate, magnesium salicylate, polyethylene glycol 4000, polyethylene glycol 6000, liquid paraffin, hydrogenated soybean oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, macrogol, synthetic aluminum silicate, anhydrous silica, higher fatty acids, higher alcohols, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, starch, sodium chloride, sodium acetate, sodium oleate, dl-leucine, and hard anhydrous silica may be used.

[0032] As additives to the liquid formulation according to the present invention, water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, monostearic acid sucroses, polyoxyethylene sorbitol fatty acid esters (tween esters), polyoxyethylene monoalkyl ethers, lanolin ethers, lanolin esters, acetic acid, hydrochloric acid, water ammonia, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethylcellulose, sodium carboxymethylcellulose, etc. may be used.

[0033] In the syrup preparation according to the present invention, a solution of white sugar, other sugars or sweeteners, etc. may be used, and if necessary, flavorings, coloring agents, preservatives, stabilizers, suspending agents, emulsifiers, viscosity enhancers, etc. may be used.

[0034] Purified water may be used in the emulsion according to the present invention, and emulsifiers, preservatives, stabilizers, fragrances, etc. may be used as needed.

[0035] In the suspension agent according to the present invention, suspending agents such as acacia, tragacanthus, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose, HPMC 1828, HPMC 2906, and HPMC 2910 may be used, and surfactants, preservatives, stabilizers, coloring agents, and fragrances may be used as needed.

[0036] The injectable preparation according to the present invention comprises solvents such as distilled water for injection, 0.9% sodium chloride injection solution, Ringer's injection solution, dextrose injection solution, dextrose + sodium chloride injection solution, PEG, lactated Ringer's injection solution, ethanol, propylene glycol, non-volatile oils—sesame oil, cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristate, and benzene benzoate; solubilizing agents such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, tween, nijungtinamide, hexamine, and dimethylacetamide; and buffers such as weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, albumin, peptone, and gums. It may include isotonic agents such as sodium chloride; stabilizers such as sodium bisulfite (NaHSO3), carbon dioxide gas, sodium metabisulfite (Na2S2O5), sodium sulfite (Na2SO3), nitrogen gas (N2), and ethylenediaminetetraacetic acid; sulfating agents such as sodium bisulfide 0.1%, sodium formaldehyde sulfoxylate, thiourea, disodium ethylenediaminetetraacetic acid, and sodium bisulfite acetone; non-inflammatory agents such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; and suspending agents such as sodium CMC, sodium alginate, Tween 80, and aluminum monostearate.

[0037] The suppository according to the present invention comprises cocoa dough, lanolin, Witepsol, polyethylene glycol, glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture of stearic acid and oleic acid, Subanal, cottonseed oil, peanut oil, palm oil, cocoa butter + cholesterol, lecithin, lanette wax, glycerol monostearate, Tween or Spandex, Imhausen, monollene (propylene glycol monostearate), glycerin, Adeps solidus, Buytyrum Tego-G, Cebes Pharma 16, hexalide base 95, Cotomar, Hydroccote SP, S-70-XXA, S-70-XX75 (S-70-XX95). Bases such as Hydrokote 25, Hydrokote 711, Idropostal, Massa estrarium (A, AS, B, C, D, E, I, T), Massa-MF, Masupol, Masupol-15, Neosupostal-N, Paramount-B, Suposiro (OSI, OSIX, A, B, C, D, H, L), suppository base type IV (AB, B, A, BC, BBG, E, BGF, C, D, 299), Supostal (N, Es), Wecobi (W, R, S, M, Fs), and Tegestor triglyceride base (TG-95, MA, 57) may be used.

[0038] Solid dosage forms for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid dosage forms are prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc., with the extract. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used.

[0039] Liquid preparations for oral administration include suspensions, oral liquids, emulsions, and syrups; in addition to commonly used simple diluents such as water and liquid paraffin, they may contain various excipients, such as humectants, sweeteners, flavorings, and preservatives. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleates.

[0040] The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level may be determined according to factors including the type and severity of the patient's disease, drug activity, sensitivity to the drug, time of administration, route of administration and elimination rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field.

[0041] The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered as a single or multiple doses. It is important to administer an amount that obtains maximum effect with a minimum amount without side effects by considering all the above-mentioned factors, and this can be easily determined by a person skilled in the art to which the present invention belongs.

[0042] The pharmaceutical composition of the present invention may be administered to an individual by various routes. All modes of administration are expected, for example, oral administration, subcutaneous injection, intraperitoneal administration, intramuscular injection, intrathecal (intradural) injection, sublingual administration, buccal mucosal administration, rectal insertion, vaginal insertion, ocular administration, ear administration, nasal administration, inhalation, spray through the mouth or nose, skin administration, transdermal administration, etc.

[0043] The pharmaceutical composition of the present invention is determined by the type of active ingredient drug, along with various relevant factors such as the disease to be treated, the route of administration, the patient's age, gender, weight, and the severity of the disease.

[0044] In the present invention, the term “individual” refers to a subject requiring treatment for a disease, and more specifically, to mammals such as humans or non-human primates, mice, rats, dogs, cats, horses, and cattle.

[0045] In the present invention, “administration” means providing a predetermined composition of the present invention to an individual by any appropriate method.

[0046] In the present invention, “prevention” refers to any act of suppressing or delaying the onset of a target disease, and “treatment” refers to any act of improving or beneficially altering the target disease and the associated metabolic abnormality symptoms by administering a pharmaceutical composition according to the present invention. Specifically, it refers to any act of administering a pharmaceutical composition containing the strain of the present invention as an active ingredient to an individual with chronic obstructive pulmonary disease to improve or benefit the symptoms of the said disease. “Improvement” refers to any act of reducing parameters related to the target disease, such as the severity of symptoms, by administering a composition according to the present invention. Specifically, it refers to any act of improving or beneficially altering the symptoms of chronic obstructive pulmonary disease by administering said composition.

[0047] In addition, the present invention provides a food composition for the prevention or improvement of chronic obstructive pulmonary disease (COPD) comprising the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) or a culture thereof as an active ingredient.

[0048] The term "food" used throughout this specification includes meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, health functional foods, and health foods, and includes all foods in the ordinary sense.

[0049] The term "health functional food" used throughout this specification refers to a food manufactured and processed using raw materials or ingredients that have functional properties useful to the human body pursuant to Article 6727 of the Health Functional Foods Act, and "functional properties" means obtaining useful effects for health purposes, such as regulating nutrients or physiological actions on the structure and function of the human body.

[0050] The food of the present invention can be manufactured by methods commonly used in the industry, and can be manufactured by adding raw materials and ingredients commonly added in the industry. Furthermore, the formulation of the food can be manufactured without restriction as long as it is a formulation recognized as a food. The food composition of the present invention can be manufactured in various forms of formulations. Unlike general pharmaceuticals, it uses food as a raw material, offering the advantage of not causing side effects that may occur with long-term use of pharmaceuticals, and possesses excellent portability; therefore, the food of the present invention can be consumed as an adjuvant to enhance the effect of improving the intestinal environment.

[0051] The above-mentioned health food refers to a food that has an active effect of maintaining or promoting health compared to general food, and the health supplement food refers to a food intended for the purpose of supplementing health. In some cases, the terms health functional food, health food, and health supplement food may be used interchangeably. Specifically, the above-mentioned health functional food refers to a food prepared by adding the strain of the present invention to food materials such as beverages, teas, spices, chewing gum, and confectionery, or by encapsulating, powdering, or suspension, and means that consuming it brings about specific health effects. Unlike general medicines, it has the advantage of not having side effects that may occur from long-term use of medicines because it is made from food.

[0052] The food composition of the present invention can be consumed on a daily basis, so a high effect on improving the intestinal environment can be expected, and thus it can be used very effectively.

[0053] The above food composition may further include a physiologically acceptable carrier, the type of carrier is not particularly limited, and any carrier commonly used in the relevant technical field may be used.

[0054] In addition, the above food composition may include additional ingredients that are commonly used in food compositions to improve odor, taste, visual appearance, etc. For example, it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantothenic acid, etc. In addition, it may include minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chromium (Cr). In addition, it may include amino acids such as lysine, tryptophan, cysteine, and valine.

[0055] In addition, the above food composition may include food additives such as preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching powder and high-grade bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), etc.), coloring agents (tar dyes, etc.), colorants (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG, monosodium glutamate, etc.), sweeteners (dulcin, cyclamate, saccharin, sodium, etc.), flavorings (vanillin, lactones, etc.), leavening agents (alum, potassium hydrogen tartrate, etc.), reinforcing agents, emulsifiers, thickeners (sizing agents), coating agents, gum bases, antifoaming agents, solvents, and improvers. The above additives can be selected according to the type of food and used in appropriate amounts.

[0056] The strain of the present invention may be added as is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The amount of the active ingredient may be appropriately determined according to its intended use (prevention, health, or therapeutic treatment). Generally, when manufacturing food or beverages, the food composition of the present invention may be added to the food or beverage in an amount of 50 parts by weight or less, specifically 20 parts by weight or less. However, when consumed over a long period for the purpose of health and hygiene, the content may be below the above range, and since there are no safety issues, the active ingredient may also be used in an amount greater than the above range.

[0057] As an example of the food composition of the present invention, it may be used as a health drink composition, in which case it may contain various flavoring agents or natural carbohydrates as additional ingredients, as in ordinary beverages. The natural carbohydrates described above may be monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; and sugar alcohols such as xylitol, sorbitol, and erythritol. Sweeteners may include natural sweeteners such as thaumatin and stevia extract; and synthetic sweeteners such as saccharin and aspartame. The proportion of the natural carbohydrates may generally be about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g per 100 mL of the health drink composition of the present invention.

[0058] In addition to the above, the health drink composition may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, or carbonating agents. Furthermore, it may contain fruit pulp for the production of natural fruit juices, fruit juice beverages, or vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health drink composition of the present invention.

[0059] The food composition of the present invention may include the strain of the present invention in various weight percent if it can show an effect of improving or preventing inflammation or asthma, and specifically, the strain of the present invention may be included in 0.00001 to 100 weight percent or 0.01 to 80 weight percent relative to the total weight of the food composition, but is not limited thereto.

[0060] In one embodiment of the present invention, the food composition may be a health functional food composition.

[0061] In addition, the present invention provides a quasi-drug composition for the prevention or improvement of chronic obstructive pulmonary disease (COPD), comprising the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) or a culture thereof as an active ingredient.

[0062] In the present invention, the term "quasi-drug" refers to articles used for the purpose of diagnosing, treating, improving, alleviating, managing, or preventing diseases of humans or animals, among which the effect is milder than that of pharmaceuticals. For example, according to the Pharmaceutical Affairs Act, quasi-drugs are defined as articles excluding those used for pharmaceutical purposes, and include products used for the treatment or prevention of diseases of humans or animals, and products that have a mild effect on the human body or do not act directly on it.

[0063] In addition, the above "quasi-drug composition" may be manufactured in a formulation selected from the group consisting of body cleansers, disinfectants, detergents, kitchen detergents, cleaning detergents, toothpaste, mouthwash, wet wipes, detergents, soaps, hand washes, hair cleansers, hair softeners, humidifier fillers, masks, ointments, and filter fillers, but is not limited thereto.

[0064] When the above-described quasi-drug composition according to the present invention is used as a quasi-drug additive, the composition may be added as is or used together with other quasi-drugs or quasi-drug ingredients, and may be used appropriately according to conventional methods. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use.

[0065] The quasi-drug composition of the present invention may, for example, be prepared in the form of a general emulsion formulation and a solubilized formulation. For example, it may have a formulation such as a lotion, cream, ointment, spray, oil gel, gel, oil, aerosol, or fogging agent, but it may be used without limitation as long as it exhibits the pest control inducing effect of the present invention. In addition, the quasi-drug composition may be used by appropriately incorporating, as necessary, oils, water, surfactants, humectants, lower alcohols having 1 to 4 carbon atoms, thickeners, chelating agents, colorants, preservatives, or fragrances that are generally incorporated into quasi-drug compositions into each formulation.

[0066] In addition, the present invention provides a method for preventing or treating chronic obstructive pulmonary disease (COPD), comprising the step of administering the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) according to the present invention or a culture thereof to an individual in need thereof.

[0067] In addition, the present invention provides the use of the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) according to the present invention for the prevention or treatment of chronic obstructive pulmonary disease (COPD).

[0068] In addition, the present invention provides a use of the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) according to the present invention for manufacturing a preparation for the prevention or treatment of chronic obstructive pulmonary disease (COPD).

[0069] A composition containing the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) according to the present invention as an active ingredient can prevent or treat chronic obstructive pulmonary disease, including emphysema, by inhibiting damage to lung tissue and suppressing immune cells. Therefore, it is expected that the present invention can help cure lung disease by eliminating the root cause of chronic obstructive pulmonary disease.

[0070] Figure 1 is a diagram showing the experimental design for confirming the lung function improvement effect of the HEM20792 strain using an emphysema mouse model.

[0071] Figures 2a and 2b show the results of confirming the effect of inhibiting lung tissue damage by HEM20792 strain treatment through H&E staining.

[0072] Figures 3a to 3c show the results of confirming the immune cell suppression effect following treatment with the HEM20792 strain through the analysis of the total number of cells and the number of immune cells.

[0073] Figures 4a and 4b show the results of confirming the immune cell suppression effect following treatment with the HEM20792 strain through immune cell ratio analysis.

[0074] Embodiments of the present invention are described below with reference to the attached drawings so that those skilled in the art can easily implement the invention. However, the present invention may be embodied in various different forms and is not limited to the embodiments described herein.

[0075] Throughout this specification, when a part is described as “comprising” a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but may include additional components. The terms “step” or “step of” used to the extent throughout this specification do not mean “step for”.

[0076] Throughout the entire specification of the invention, the term “combination(s) of these” included in the Markush-style expressions means one or more mixtures or combinations selected from the group consisting of the components described in the Markush-style expressions, and means including one or more selected from the group consisting of said components.

[0077] [Example]

[0078] Example 1. Experimental design to confirm the lung function improvement effect of the HEM20792 strain

[0079] The effects of administering two candidate strains for emphysema improvement to a smoking-exposed emphysema mouse model were confirmed. The two candidate strains for emphysema improvement are Lactobacillus sakei HEM20224 and Lactobacillus fermentum HEM20792 (KCTC 14066BP). The experiment consisted of a CTL group with no treatment, an SM group treated only with smoking, an SM+HEM20224 group treated with smoking and HEM20224, and an SM+HEM20792 group treated with smoking and HEM20792.

[0080] Six-week-old female C57BL / 6 mice were acclimatized for one week, after which strains HEM20224 or HEM20792 were administered to the respective groups once per day for five days per week for a total of six weeks, starting two weeks prior to the smoking experiment. After two weeks of strain administration, the SM, SM+HEM20224, and SM+HEM20792 groups were exposed to smoking in an inhalation chamber for a total of four weeks, at a rate of four cigarettes per session, three times per day, and five days per week. During the four-week smoking exposure period, poly I:C (polyinosinic:polycytidylic acid) was administered intranasally during the third and fourth weeks at a rate of 50 μl / mouse, once per day, for a total of two weeks during the final two weeks. The experimental design is shown in Figure 1.

[0081] Example 2. Confirmation of the inhibitory effect of HEM20792 strain on lung tissue damage

[0082] To determine the effect of the candidate strain on the decline in lung function caused by emphysema in vivo, mouse lungs were isolated, and the excised left lung lobe was immersed in a 4% paraformaldehyde (PFA) solution for at least one day. Subsequently, the pre-treated tissue was prepared into paraffin blocks, sliced ​​to a thickness of approximately 5 μm, and attached to slides. These lung tissue sections were stained with hematoxylin and eosin (H&E) and quantitatively expressed using the Mean Linear Intercept (MLI) value. MLI is a quantitative measurement method used in biology and other fields to estimate the average size of features visible in microscopic images, such as tissue cells. The results are shown in Figures 2a and 2b.

[0083] As shown in Figures 2a and 2b, the MLI values ​​in this experiment increased with smoking, and the SM+HEM20792 group showed significantly lower values ​​compared to the smoking (SM) group and the SM+HEM20224 group. Through this, it was confirmed that while the lung tissue of the control group that was not administered the strain or was administered the HEM20224 strain was disintegrated, lung tissue damage was suppressed in the experimental group administered the HEM20792 strain.

[0084] Example 3. Confirmation of the immunosuppressive effect of HEM20792 strain 1 - Related to cell number

[0085] To determine the effect of the candidate strain on the composition of lung immune cells in vivo, a portion of the mouse trachea was incised, and 1 ml of sterile phosphate-buffered saline (PBS) was added and then withdrawn twice to obtain approximately 2 ml of bronchoalveolar lavage fluid (BALF). Subsequently, the BALF was centrifuged at 2200 rpm for 10 minutes at 4°C, and the supernatant was collected separately. 0.5 ml of PBS was added to the cell pellet to suspend the cells. These cells were then distributed at a rate of 1 x 10⁶ per sample. 5 After diluting the liquid sample in PBS to a concentration of 0.5 ml / cells, the cells were attached to a microscope slide using a cytocentrifuge at 600 rpm for 5 minutes. Then, the cells were stained using Diff-Quid (Sysmex) reagent, and the number of lymphocytes and neutrophils in the total alveolar lavage fluid was measured. The results are shown in Figures 3a to 3c.

[0086] As shown in Figures 3a to 3c, in this experiment, the total number of cells, lymphocytes, and neutrophils decreased in the SM+HEM20792 group compared to the smoking (SM) group and the SM+HEM20224 group. Through this, it was confirmed that the HEM20792 strain may be useful for the treatment of lung diseases such as COPD by inducing a decrease in immune cells or suppressing the immune response.

[0087] Example 4. Confirmation of the immunosuppressive effect of HEM20792 strain 2 - Related to cell ratio

[0088] To determine the effect of the candidate strain on the composition of lung immune cells in vivo, lung tissue was pulverized using Type I collagenase (Sigma), Type IV collagenase (Sigma), and Denase I (Sigma) Hyaluronidase (Sigma) in RPMI 1640 (Roswell Park Memorial Institute 1640) medium at 37°C for 30 minutes, and the pulverized tissue was passed through a cell strainer to obtain a single-cell suspension. Subsequently, cells were stained with monoclonal antibodies of anti-mouse CD3-FITC (BioLegend, San Diego, CA, USA), CD4-PerCP / Cy5.5 (BioLegend), CD8-APC / Cy7 (BioLegend), CD45-Pacific blue (BioLegend), F4 / 80-BV510 (BioLegend), CD11b-PE / Cy7 (BioLegend), IFNr-APC (BioLegend), and IL17-PE (BioLegend). In addition, flow cytometry was performed using a BX FACSCanto II flow cytometer (BD Bioscience, San Jose, CA, USA), and the results were analyzed using FolwJo software (TreeStar, Ashland, OR, USA). The results are shown in Figures 4a and 4b.

[0089] As shown in Figures 4a and 4b, the ratio of immune cells in this experiment was measured, and the ratio of macrophages and CD8+IL-17+IFNr- was significantly reduced in the SM+HEM20792 group compared to the smoking (SM) group. Through this, it was confirmed that the HEM20792 strain alters the immune cell profile in lung tissue and, in particular, by reducing the number of inflammatory cells, may be useful for the treatment of lung diseases such as COPD.

[0090]

Claims

1. A pharmaceutical composition for the prevention or treatment of chronic obstructive pulmonary disease (COPD), comprising the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) or a culture thereof as an active ingredient.

2. In Paragraph 1, A pharmaceutical composition in which the above chronic obstructive pulmonary disease (COPD) is emphysema or chronic bronchitis.

3. In Paragraph 1, The above strain is a pharmaceutical composition that inhibits damage to lung tissue.

4. In Paragraph 3, A pharmaceutical composition in which the above damage is caused by smoking or secondhand smoke.

5. In Paragraph 1, A pharmaceutical composition in which the strain reduces one or more selected from the group consisting of lymphocytes, neutrophils, macrophages, and CD8+IL-17+IFNr-.

6. A food composition for the prevention or improvement of chronic obstructive pulmonary disease (COPD), comprising Lactobacillus fermentum HEM20792 strain (KCTC14066BP) or a culture thereof as an active ingredient.

7. In Paragraph 6, A food composition in which the above chronic obstructive pulmonary disease (COPD) is emphysema or chronic bronchitis.

8. In Paragraph 6, The above strain is a food composition that inhibits damage to lung tissue.

9. In Paragraph 8, A food composition in which the above damage is caused by smoking or secondhand smoke.

10. In Paragraph 6, A food composition in which the strain reduces one or more selected from the group consisting of lymphocytes, neutrophils, macrophages, and CD8+IL-17+IFNr-.

11. A quasi-drug composition for the prevention or improvement of chronic obstructive pulmonary disease (COPD), comprising Lactobacillus fermentum HEM20792 strain (KCTC14066BP) or a culture thereof as an active ingredient.

12. A method for the prevention or treatment of chronic obstructive pulmonary disease (COPD), comprising the step of administering the Lactobacillus fermentum HEM20792 strain (KCTC14066BP) or a culture thereof to an individual in need thereof.

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