Composition comprising codonopsis lanceolata, saururus chinensis, platycodon grandiflorum, and propolis as active ingredients for preventing, alleviating, or treating respiratory diseases

Abstract

The present invention relates to a composition for preventing, alleviating, or treating respiratory diseases, the composition comprising Codonopsis lanceolata, Saururus chinensis, Platycodon grandiflorum, and propolis as active ingredients. The composition according to the present invention was proven to be effective in preventing, alleviating or, treating respiratory diseases on the basis of experiments using a mouse fibroblast cell model.

Description

A composition for the prevention, improvement, or treatment of respiratory diseases comprising Codonopsis pilosula, Triosteum sinense, Platycodon grandiflorus, and propolis as active ingredients The present invention is a composition for the prevention, improvement, or treatment of respiratory diseases comprising Codonopsis pilosula, Triosteum sinense, Platycodon grandiflorus, and propolis as active ingredients. This invention is a result of a project supported by the Korea Bio-Specialized Center Association, and the project information is as follows. 1. Project No.: B0080207002074 2. Business Registration No.: KBC-001 3. Ministry Name: Ministry of Trade, Industry and Energy 4. Name of Project Management Agency: Korea Institute for Industrial Technology Advancement (KIAT) 5. Research Project Title: Global Competitiveness Enhancement Project for Bioactive Agents 6. Project Period: March 8, 2024 – October 31, 2024 Asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis, cough suppressants, acute and chronic bronchitis, bronchiolitis, pharyngitis, tonsillitis, and laryngitis are representative respiratory diseases. Asthma refers to chronic inflammation occurring in the airways, specifically the bronchi. Inflammation caused by asthma can be exacerbated by a wide variety of predisposing factors, such as exhaust fumes, allergens, cold wind, exercise, and respiratory infections; persistent inflammation leads to airway deformation and hyperresponsiveness. These causes result in general symptoms such as wheezing (a whistling or rattling breathing sound due to narrowed airways), shortness of breath, coughing, and the expulsion of excessive sputum. The prior art literature is as follows. (Patent Document 1) describes a composition for improving respiratory diseases or respiratory function comprising Codonopsis pilosula extract. Upon examination, it describes a composition for improving respiratory diseases prepared using a mixture of Codonopsis pilosula extract, pear extract, jujube fruit extract, Angelica gigas extract, and black garlic extract. (Claim 1, Identification Item

[0017] (See below) (Patent Document 2) describes a composition for preventing or treating inflammatory respiratory diseases caused by fine dust, comprising a mixed extract of mugwort and *Sambaeckcho*. Upon examination, it is stated that an extract obtained by mixing mugwort and *Sambaeckcho* in a weight ratio of 6:4 serves as the active ingredient, and furthermore, that the higher the proportion of mugwort, the greater the cell protective effect against fine dust. (Claim 1, Identification Item

[0130] (See below) (Patent Document 3) describes a composite preparation for improving respiratory inflammation induced by fine dust. Upon examination, it describes a composite preparation for improving fine dust-induced respiratory inflammation characterized by containing a complex extract of Platycodon grandiflorus, Glycyrrhiza glabra, Lonicera japonica, and Morus alba bark as an active ingredient, and states that Example 1, extracted by mixing in a weight ratio of 7:3:7:3, shows the best effect. (Claim 1, Identification Item

[0040] ,

[0087] (See below) Patent Document 4 describes a food composition for improving respiratory diseases using natural products and a method for manufacturing the same. Upon examination, a step of preparing a syrup by mixing a concentrated extract of mixed herbal medicines with propolis, etc., is described. (See Claim 1) The first problem to be solved is to provide a composition for improving respiratory diseases without side effects using natural materials. Solution 1 is, This is a health functional food composition for preventing or improving respiratory diseases, comprising a mixed extract of Codonopsis lanceolata, Saururus chinensis, Platycodon grandiflorum, and propolis as an active ingredient. Solution 2 is, In Solution 1, The above mixed extract is, A health functional food composition for preventing or improving respiratory diseases, characterized by extracting a mixture of Codonopsis pilosula, Triosteum sinense, Platycodon grandiflorus, and propolis in a weight ratio of 1:1:1:1. Solution 3 is, In solution means 1 or 2, The above-mentioned mixed extract is characterized by a concentration of 15.6 ug / mL to 31.3 ug / mL, and is a health functional food composition for preventing or improving respiratory diseases. Solution 4 is, It is a pharmaceutical composition for the prevention or treatment of respiratory diseases, comprising a mixed extract of Codonopsis lanceolata, Saururus chinensis, Platycodon grandiflorum, and propolis as an active ingredient. Effect 1 is that the composition according to the present invention is a composition using natural materials and has no side effects. Effect 2 is that the composition according to the present invention showed efficacy in preventing or treating respiratory diseases by reducing inflammatory factors in animal cell experiments. Figure 1 is a graph showing the results of the cytotoxicity analysis of the mixed extract. Figures 2 to 4 are graphs showing the experimental results comparing the effects of the mixed extract on the production of inflammatory cytokines. Preparation Example 1. Mixed extract of Codonopsis pilosula, Triosteum sinense, Platycodon grandiflorus, and propolis Codonopsis lanceolata, Saururus chinensis, Platycodon grandiflorum, and propolis are each ground and used. Depending on the design conditions, the propolis may be used as a powder obtained by extracting the raw material in ethanol for 3 to 10 days, filtering, and drying. Codonopsis pilosula, Triosteum sinense, Platycodon grandiflorus, and propolis are mixed in a weight ratio of 1:1:1:1 (used as CSPPr samples in the following experimental examples), and then distilled water (10 times the amount) is added and hot water extraction or ethanol extraction is performed. Preferably, extraction is performed at 70 to 80°C for 3 hours. Depending on the design conditions, the supernatant separated after filtering the first extract may be mixed with the supernatant of a second extract obtained by adding an equal amount of distilled water to the remaining residue. Experimental Example 1. Analysis of Cytotoxicity of Mixed Extract The A549 cell line derived from lung cancer supplied by ATCC (Maryland, USA) was used. The culture medium consisted of RPMI 1640 (Flow Lab, USA) medium supplemented with 15% fetal bovine serum, 100 µg / ml penicillin, and 100 µg / ml streptomycin. After dispensing into a 96-well plate, MTT solution was added and incubated for 3 hours. Then, solubilization buffer was added, followed by incubation at 37°C for 10 min, and values ​​were measured at 570 nm using an ELISA reader. The cytotoxicity of the mixed extract of Codonopsis pilosula, Triosteum sinense, Platycodon grandiflorus, and propolis prepared in Preparation Example 1 was analyzed. Figure 1 is a graph showing the results of the cytotoxicity analysis of the mixed extract. As seen, cytotoxicity was observed in the range exceeding 31.3 µg / mL. Experimental Example 2. Effects on inflammation-inducing factors A cell model induced by PM(2.5) / LPS was constructed using the NIH3T3 cell line derived from mouse embryonic fibroblasts and used for experiments. (PM(2.5); fine dust) Inflammatory mediators of inflammatory cytokines were quantified in the cell supernatant using the Enzyme-linked Immunosorbent Assay (ELISA). The ELISA was performed using a Mouse ELISA kit for TNF-α, IL-1β, and IL-6 purchased from BD Pharmaingen (CA, USA). Protein levels of pro-inflammatory cytokines were measured using the ELISA method. Measurements were taken after pre-treating the experimental group for 1 hour. The experimental groups are as follows: untreated group (labeled 'CON'), PM+LPS treated group (labeled 'PM'), PM+LPS+Codonopsis pilosula+Sambaeckia tricuspidata+Platycodon grandiflorus treated group (labeled 'CSP', mixed extract with a weight ratio of 1:1:1), PM+LPS+Codonopsis pilosula+Sambaeckia tricuspidata+Propolis treated group (labeled 'CSPr', mixed extract with a weight ratio of 1:1:1), PM+LPS+Sambaeckia tricuspidata+Platycodon grandiflorus+Propolis treated group (labeled 'SPPr', mixed extract with a weight ratio of 1:1:1), PM+LPS+Codonopsis pilosula+Platycodon grandiflorus+Propolis treated group (labeled 'CPPr', mixed extract with a weight ratio of 1:1:1), PM+LPS+Codonopsis pilosula+Sambaeckia tricuspidata+Platycodon grandiflorus+Propolis treated group (labeled 'CSPPr', mixed extract with a weight ratio of 1:1:1:1, Preparation Example 1) Figures 2 to 4 are graphs showing the experimental results comparing the effects of the mixed extract on the production of inflammatory cytokines. As seen, the inflammatory cytokines TNF-α, IL-1β, and IL-6 were reduced in both the experimental groups using three of the four materials and the experimental group using the mixed extract with all four materials, and were reduced more in the experimental group using four materials prepared according to Example 1 compared to the experimental group using three materials. Example 1. Composition for improving respiratory diseases containing the mixed extract according to Preparation Example 1 as an active ingredient Based on the above preparation and experimental examples, Example 1 includes a mixed extract according to Preparation Example 1 as an active ingredient of the composition. For example, the composition according to the present invention includes a mixed extract of Codonopsis pilosula, Triosteum sinense, Platycodon grandiflorus, and propolis mixed in a weight ratio of 1:1:1:1 as an active ingredient. Preferably, the concentration of each extract is included in a range of 15.6 µg / mL to 31.3 µg / mL. Depending on the design conditions, the concentration of the mixed extract may be varied within a range that satisfies the solution principle of the present invention. The present invention may provide a formulation formed into a pharmaceutical unit dosage form by adding the above-mentioned mixed extract as an active ingredient and a pharmaceutically acceptable carrier, excipient, or diluent. Herein, carriers, excipients, and diluents may include toz, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition, the above pharmaceutical dosage form may also be used in the form of a pharmaceutically acceptable salt, and may also be used alone, in combination with other pharmaceutically active compounds, or in a suitable combination. Furthermore, when formulating the above active ingredient, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. In addition, the above pharmaceutical dosage form may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, as well as topical preparations, suppositories, and sterile injectable solutions, each according to conventional methods. The above solid formulation for oral administration may be prepared by mixing at least one excipient with the extract, for example, starch may be calcium carbonate, sucrose or lactose, gelatin, etc. In addition, lubricants such as magnesium stearate and talc may also be used in addition to simple excipients. The above-mentioned formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. The above-mentioned non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Witepsol, Macrogol, Tween 61, Cacao, Laurin, Glycerozelatin, etc. can be used as bases for suppositories. The preferred dosage of the extract of the present invention varies depending on the patient's condition and body weight, the severity of the disease, age, gender, drug form, route of administration, and duration, but can be appropriately selected by those skilled in the art. However, for a desirable effect, it is preferable to administer the extract of the present invention at a dose of 0.001 to 300 mg / kg, and the administration may be given once a day or divided into several doses. The above dosage does not limit the scope of the present invention in any way. The extract of the present invention can be administered to mammals such as rats, mice, livestock, and humans by various routes. Any mode of administration is expected, for example, by oral, rectal, or intravenous, intramuscular, or subcutaneous injection. A health functional food composition can be provided by adding a food auxiliary additive to the active ingredient of the present invention. Foods to which the above active ingredient can be added include, for example, various types of food products, beverages, chewing gum, tea, vitamin complexes, health functional foods, etc. The amount of the above-mentioned active ingredient in the food or beverage may be added in an amount of 0.01 to 20 weight percent of the total weight of the food or beverage, and the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g, based on 100 ml. As described above, the present invention is a composition using natural materials and has no side effects. Furthermore, the composition according to the present invention can improve chronic obstructive pulmonary disease and respiratory diseases in a chronic obstructive pulmonary disease cell model. The health functional beverage composition of the present invention has no particular limitations on other ingredients besides the extract mentioned above, and may contain various flavoring agents or natural carbohydrates as additional ingredients, as in conventional beverages. Examples of the natural carbohydrates mentioned above include monosaccharides, e.g., glucose, fructose; disaccharides, e.g., maltose, sucrose, etc.; polysaccharides, e.g., dextrin, cyclodextrin, etc.; and sugar alcohols such as xylitol, sorbitol, erythritol, etc. In addition to those mentioned above, natural flavoring agents (taumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) may be advantageously used as flavoring agents. The proportion of the natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g, per 100 ml of the composition of the present invention. In addition to the above, the composition of the present invention may contain various nutritional agents, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the composition of the present invention may contain fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not particularly important, it is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention. When the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent, or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan. In the case where the formulation of the present invention is a suspension, liquid diluents such as water, ethanol, or propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracanthese may be used as carrier components. In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, it may additionally include a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether. So far, the present invention has been examined focusing on preferred embodiments. The embodiments described in this specification and the configurations illustrated in the drawings relate to the most preferred embodiment of the present invention and do not represent all technical aspects of the present invention; therefore, it should be understood that there may be various equivalents and modified examples that can replace them. Accordingly, the present invention is not limited to the embodiments presented, and there may be embodiments that allow for various modifications and changes within the scope of the technical concept of the present invention and the equivalent scope of the technical concept described in the claims below, by those skilled in the art to which the present invention belongs.

Claims

1. A health functional food composition for preventing or improving respiratory diseases, comprising a mixed extract of Codonopsis lanceolata, Saururus chinensis, Platycodon grandiflorum, and propolis as an active ingredient.

2. In Claim 1, The above mixed extract is, A health functional food composition for preventing or improving respiratory diseases, characterized by extracting a mixture of Codonopsis pilosula, Triosteum sinense, Platycodon grandiflorus, and propolis in a weight ratio of 1:1:1:

1.

3. In claim 1 or 2, A health functional food composition for preventing or improving respiratory diseases, characterized in that the concentration of the above-mentioned mixed extract is 15.6 ug / mL to 31.3 ug / mL.

4. A pharmaceutical composition for the prevention or treatment of respiratory diseases, comprising a mixed extract of Codonopsis lanceolata, Saururus chinensis, Platycodon grandiflorum, and propolis as an active ingredient.

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