KR102318414B1 - Composition of improvement, prevention and treatment in Chronic obstructive pulmonary disease with yeast extract - Google Patents

Abstract

The present invention uses dry yeast extract as an active ingredient to prevent the destruction of elastin in the alveoli, and to prevent alveolar damage by inhibiting the death of alveolar epithelial cells to improve chronic obstructive pulmonary disease induced by secondhand smoke, It relates to a composition effective for prevention or treatment.

Description

A composition for improving, preventing or treating chronic obstructive pulmonary disease containing yeast extract as an active ingredient {Composition of improvement, prevention and treatment in Chronic obstructive pulmonary disease with yeast extract}

The present invention relates to a composition for improving, preventing or treating chronic obstructive pulmonary disease, comprising a dry yeast extract as an active ingredient, and more particularly, prevents the destruction of elastin in the alveoli, and inhibits the death of alveolar epithelial cells By preventing damage to the alveoli, it relates to a composition effective in improving, preventing or treating chronic obstructive pulmonary disease induced by secondhand smoke.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease in which an abnormal inflammatory reaction occurs in the lungs due to inhalation of harmful particles or gases, gradually restricting airflow, leading to decreased lung function and respiratory distress. . Representative chronic obstructive pulmonary diseases include emphysema and chronic bronchitis, and in particular, when the alveoli are destroyed, regeneration is impossible, and once damaged, it is impossible to recover.

Worldwide, 329 million people, or close to 5% of the world's population, have chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) was the third leading cause of death in 2012 and the cause of death for more than 3 million people. Chronic obstructive pulmonary disease is mainly caused by smoking, and in recent years, an increase in soot and fine dust due to rapid industrialization is one of the main causes of chronic obstructive pulmonary disease. It also results in a significant level of chronic inflammatory response to inhalation of irritants, and chronic bacterial infection may also be added to this inflammatory condition.

Inflammatory cells involved in chronic bacterial infection include two types of leukocytes, neutrophilic granulocytes and macrophages. In smokers, Tc1 lymphocytes are added, and in some patients with chronic obstructive pulmonary disease, asthma-like eosinophils are added. These cellular responses are, in part, induced by inflammatory mediators such as chemotaxis. Other processes involved in lung injury include oxidative stress caused by free radicals contained in high concentrations in cigarette smoke and resolved by inflammatory cells, and damage to connective tissue in the lungs caused by insufficient inhibition of protease by protease inhibitors. Damage to the connective tissue of the lungs leads to emphysema, which leads to poor airflow and, ultimately, to poor absorption and release of respiratory gases. General muscle degeneration, which is often seen in chronic obstructive pulmonary disease, may be due to inflammatory mediators released from some lungs into the blood.

Conventionally, various studies have been conducted for the prevention and treatment of chronic obstructive pulmonary disease, and there is a need for a method for preventing and treating chronic obstructive pulmonary disease using an effective and non-harmful component to the human body.

Republic of Korea Patent No. 10-1811207 (Registration date: December 15, 2017) describes a composition for treating, improving or preventing lung disease, which contains an extract of oyster leaf, birch bark extract, or chaga mushroom extract as an active ingredient. have.

An object of the present invention is to provide a composition containing a safe new material that can improve chronic obstructive pulmonary disease caused by secondhand smoke as an active ingredient.

The present invention provides a food composition for improving chronic obstructive pulmonary disease, characterized in that it contains a dry yeast extract as an active ingredient.

In the food composition of the present invention, the chronic obstructive pulmonary disease may be caused by smoking, preferably.

On the other hand, the present invention provides a pharmaceutical composition for the treatment or prevention of chronic obstructive pulmonary disease, characterized in that it contains a dry yeast extract as an active ingredient.

In the pharmaceutical composition of the present invention, the chronic obstructive pulmonary disease may be caused by smoking, preferably.

The present invention contains a dry yeast extract capable of improving, preventing or treating chronic obstructive pulmonary disease induced by secondhand smoke as an active ingredient by inhibiting the death of alveolar epithelial cells and inhibiting the destruction of elastin in the alveoli. compositions can be provided.

1 is a graph of experimental results measuring the effect of dry yeast extract of the present invention on the number of immune inflammatory cells in lung lavage of a secondhand smoke mouse model.
Figure 2 is a photograph of the result of observing the degree of alveolar destruction and the expression pattern of the elastin degrading enzyme MMP-12 (omatrix metalloprotease-12) by treating the dry yeast extract in the alveoli of the secondhand smoke mouse model.
3 is a graph of the results of observing the BAX/BCL-2 protein expression pattern related to alveolar cell death by treating the dry yeast extract of a secondhand smoke mouse model.

The present invention provides a food composition for improving chronic obstructive pulmonary disease, characterized in that it contains a dry yeast extract as an active ingredient. In addition, there is provided a composition for treating or preventing chronic obstructive pulmonary disease, characterized in that it contains a dry yeast extract as an active ingredient.

Yeast is a microorganism used to make bread, beer, wine, etc. It is a group of fungi or mushrooms, but it is a generic term for single-celled organisms that do not have mycelium and do not have photosynthetic or motility. Dried yeast is called 'dry yeast', and it is dried in order to be able to store it because the yeast has a lot of moisture and is easy to spoil. Mainly dry yeast should be dried so that the yeast does not die, and the drying method is not particularly limited, for example, drying by ventilation at low temperature, drying at a temperature of about 30°C for 8 hours, drying by rotating in the horizontal direction and a method of air drying in a barrel, and most preferably freeze-drying in order to suppress the death of yeast by heat.

For the production of yeast extract, first, water corresponding to 5 to 10 times the weight of the yeast is added to dry yeast, incubated for 1 to 5 hours at room temperature to activate the yeast, and then extracted at 50 to 88 ° C. for 0.5 to 5 hours. and filter to remove yeast to obtain yeast extract and concentrate it so that the solid content is 10% (w/v) or more. The concentrated yeast extract is filtered through an ultrafiltration membrane in a system equipped with a filtration membrane with a molecular weight of 5,000 to 20,000 Daltons to remove low molecular weight components passing through the ultrafiltration membrane, and the resulting solution is concentrated again and freeze-dried to finally obtain a dry yeast extract. do.

The volume of water added for extraction is usually determined and does not affect the technical idea of the present invention even if it is 5 times or less or 10 times or more. In addition, since the extraction time is also set from an economical point of view, when it is shorter than 0.5 hours, the extraction efficiency is lowered, when it is longer than 5 hours, the efficiency of the system is lowered, and the yield and activity are affected in obtaining the yeast extract. The extraction temperature is one of the factors that have a great influence on the efficiency, and the higher the temperature, the higher the extraction yield tends to be. To apply the ultrafiltration system, a filtration membrane having a molecular weight of 5,000 to 30,000 Daltons can be used, and more preferably, a filtration membrane having a molecular weight of 15,000 Daltons can be used. The reason for applying the ultrafiltration system is to remove low molecular weight substances as a method to increase the activity per unit weight.

According to the following experiment, the dry yeast extract of the present invention was It was confirmed to reduce the number of each inflammatory cell in the mouse model, and inhibit the destruction of the alveoli, the destruction of elastic fiber elastin in the alveoli, and apoptosis of the alveolar cells. elastin), the dry yeast extract of the present invention can be said to be effective in improving, treating or preventing chronic obstructive pulmonary disease induced by secondhand smoke.

On the other hand, the food composition of the present invention is, for example, meat, grains, caffeinated beverages, general drinks, chocolate, breads, snacks, confectionery, pizza, jelly, noodles, gums, ice cream, alcoholic beverages, alcohol, vitamin complexes and other health It may be any one selected from supplements, but is not necessarily limited thereto.

On the other hand, the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, diluent or excipient. Usable carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, There are microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, and at least one selected from among them may be used. In addition, when the therapeutic and prophylactic agent is a pharmaceutical, a filler, an anti-aggregant, a lubricant, a wetting agent, a fragrance, an emulsifier, or a preservative may be additionally included.

On the other hand, the dosage form of the pharmaceutical composition of the present invention may be prepared in a desired form according to the method of use, and in particular, methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal It is better to adopt and formulate it. Examples of specific formulations include PLASTERS, GRANULES, LOTIONS, LINIMENTS, LEMONADES, AROMATIC WATERS, POWDERS, syrups ( SYRUPS, OPHTALMIC OINTMENTS, LIQUIDS AND SOLUTIONS, AEROSOLS, EXTRACTS, ELIXIRS, OINTMENTS, FLUIDEXTRACTS, EMULSIONS ), suspensions (SUSPESIONS), premises (DECOCTIONS), infusions (INFUSIONS), eye drops (OPHTHALMIC SOLUTIONS), tablets (TABLETS), suppositories (SUPPOSITIORIES), injections (INJECTIONS), alcohol tablets (SPIRITS), CATAPLS ), capsules (CAPSULES), creams (CREAMS), troches (TROCHES), tinctures (TINCTURES), pastas (PASTES), pills (PILLS), it may be any one selected from soft or hard gelatin capsules.

On the other hand, in the pharmaceutical composition of the present invention, the dosage is preferably determined in consideration of the administration method, the age, sex and weight of the user, and the severity of the disease. For example, based on the dry yeast extract as an active ingredient, 0.000001 to 100 mg/kg (body weight) per day can be orally administered at least once. However, the above dosage is only an example for illustration, and may be changed by the condition of the user and the prescription of the doctor.

Meanwhile, in the present invention, the meaning of 'containing as an active ingredient' means that the improvement, prevention or treatment efficacy of chronic obstructive pulmonary disease required in the present invention is generated from the dry yeast extract, which is a component of the present invention, and other It means that it can be included as an auxiliary ingredient with other ingredients.

Hereinafter, the contents of the present invention will be described in more detail through the following Examples and Experimental Examples. However, the scope of the present invention is not limited only to the following examples and experimental examples, and includes modifications of technical ideas equivalent thereto.

[Preparation Example 1: Preparation of dry yeast extract]

In this embodiment A dried yeast extract was prepared using (culture) the yeast, Saccharomyces cerevisiae. Dry yeast is sold as Baker's yeast, beer yeast, etc., and products sold as dry yeast for the production of various types of yeast extracts are also applicable. In this embodiment, Baker's yeast produced by Choyang Chemical is mainly used. was used.

For the preparation of yeast extract, 5 times water is added to 1 kg of dry yeast, and after incubation for 3.5 hours at room temperature for yeast activation, it is extracted again at 75 degrees Celsius for 4.5 hours, filtered yeast, and then the obtained extract is concentrated. , was filtered through a membrane having a molecular weight of 15,000 Daltons in an ultrafiltration membrane system to remove low molecular weight substances, and the remaining solution was freeze-dried to finally obtain 88 g.

[Example 1: Efficacy confirmation experiment for chronic obstructive pulmonary disease of the dry yeast extract of the present invention]

In this example, by treating the dry yeast extract prepared in Preparation Example 1 in a mouse model induced by secondhand smoke, it was attempted to confirm the efficacy of the dry yeast extract for chronic obstructive pulmonary disease.

First, 5-week-old BALb/C mice were induced into a chronic obstructive pulmonary disease model by exposing 5-week-old BALb/C mice to an experimental cigarette (3R4F) purchased from the University of Kentucky, USA, for 8 weeks, 5 days a week, for 8 weeks after a one-week adaptation period.

(1) Effect of dry yeast extract using alveolar lavage fluid in secondhand smoke mouse model on the number of various immune inflammatory cells

After inserting a syringe into the airway of the second-hand smoke mouse model, and washing the lungs with phosphate buffer saline (PBS), dry yeast extract was administered intragastrically at concentrations of 50, 100, and 200 mg/kg 5 days a week. Thereafter, the number of various immune inflammatory cells was measured through an animal hemocytometer. The immune inflammatory cells used in the experiment were white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils. .

As a result, as shown in FIG. 1, when comparing each of the immune inflammatory cells induced by secondhand smoke and the dry yeast extract treatment, most of the immune inflammatory cells showed a decrease in the number of immune inflammatory cells than the control group in which secondhand smoke was not induced. could check This suggests that dry yeast extract can be used as a material to reduce inflammation induced by secondhand smoke.

(2) Effect of dry yeast extract on alveolar cells and alveolar elastin in secondhand smoke mouse model

In this experimental example, the effect of the dry yeast extract prepared in Example 1 on alveolar cells and alveolar elastin of a mouse model induced by secondhand smoke was examined.

First, from airway epithelial cells, 10% SDS, 1% glycerophosphate, 0.1 mol/L Na ₃ VO ₄ , 0.5 mol/L NaF and 1 mol/L containing a protease inhibitor cocktail, Lungs were sampled using a homogenizer using Tris-HCl (pH 6.8) lysis buffer, and then protein content was quantified using a Lowry assay method. Lung samples were mixed with 5X dye, boiled at 95°C for 10 minutes, and then electrophoresed on 8-15% SDS-polyacrylamide gel to separate proteins. After the electrophoresis was completed, it was transferred to a nitrocellulose membrane. The membrane was blocked in 5% nonfat dry milk for 3 hours, and after attaching a specific primary antibody, overnight at 4°C. After washing with TBS-T, the secondary antibody was reacted with anti-mouse IgG conjugated horse-radish peroxidase for 1 hour, and then band pictures were taken with an X-ray film using an ECL solution.

The excised lungs were fixed using 4% formaldehyde solution, made into paraffin blocks, cut into 5 μm thick slides, and then observed by staining with hematoxylin and eosin. Immunostaining was performed overnight at 4°C after blocking with 3% BSA solution and attaching a specific primary antibody. After washing with TBS-T, secondary antibody anti-rabbit IgG conjugated FITC was applied for 1 hour, and protein expression was confirmed through a fluorescence microscope.

In general, elastin, a component abundant in the lung connective tissue that connects the alveoli to each other, is known to play a role in increasing the elasticity of the lung itself. When elastin is reduced, the elasticity of the lungs is reduced and various lung diseases such as pulmonary emphysema may occur. MMP-12 (matrix metalloprotease-12) is a representative enzyme that decomposes elastin.

In this regard, as a result of confirming the effect of the dry yeast extract on the alveoli of the second-hand smoke-induced mouse model, the dry yeast extract was In the group treated with 50, 100, and 200 mg/kg concentration, it was observed that the degree of alveolar destruction was suppressed. In addition, as a result of confirming the expression pattern of MMP-12 in the alveoli of the second-hand smoke-induced mouse model, it was confirmed that the expression level was suppressed when the dry yeast extract was treated.

On the other hand, in order for apoptosis to occur, proteins such as BAX and BCL-2 are involved to regulate intracellular signaling pathways, and BAX is known to induce apoptosis by interfering with BCL2, a protein that prevents apoptosis. In this regard, the purpose of this study was to determine the effect on the death of alveolar cells by treating the dry yeast extract in a secondhand smoke mouse model. As a result, as shown in FIG. 3 , when the expression level of BAX protein increased and the expression level of BCL-2 decreased in the mouse model induced by secondhand smoke compared to the control group, the dry extract was administered at 50, 100, 200 mg/ In the group treated with the kg concentration, it was confirmed that the expression level of BAX protein decreased and the expression level of BCL-2 increased in a concentration-dependent manner. Through this, it can be seen that the dry yeast extract can be used as a material that inhibits the destruction of alveoli caused by secondhand smoke, the destruction of elastin in the alveoli, and alveolar cell death.

In summary, dry yeast extract reduces inflammation induced by secondhand smoke, and inhibits alveolar destruction, elastin destruction in alveoli, and alveolar cell death, thereby showing efficacy in improving, preventing or treating chronic obstructive pulmonary disease. It was confirmed that the material could be used.

Claims (4)

Contains dry yeast extract as an active ingredient,
The dry yeast extract is obtained by adding water corresponding to 5 to 10 times the weight of the yeast to dry yeast, culturing at room temperature for 1 to 5 hours, extracting at 50 to 88 ° C. for 0.5 to 5 hours, filtering, and concentrating. After obtaining the yeast extract concentrate, the yeast extract concentrate was filtered with an ultrafiltration membrane having a molecular weight of 15,000 Daltons to remove low molecular weight substances and the remaining liquid was obtained. A food composition for improving emphysema, characterized in that it improves.
According to claim 1,
The emphysema is
A food composition for improving emphysema, characterized in that it is caused by smoking.
Contains dry yeast extract as an active ingredient,
The dry yeast extract is obtained by adding water corresponding to 5 to 10 times the weight of the yeast to dry yeast, culturing at room temperature for 1 to 5 hours, extracting at 50 to 88 ° C. for 0.5 to 5 hours, filtering, and concentrating. After obtaining the yeast extract concentrate, the yeast extract concentrate was filtered with an ultrafiltration membrane having a molecular weight of 15,000 Daltons to remove low molecular weight substances and the remaining liquid was obtained. A pharmaceutical composition for the treatment or prevention of emphysema, characterized in that it is treated or prevented.
4. The method of claim 3,
The emphysema is
A pharmaceutical composition for the treatment or prevention of emphysema, characterized in that it is caused by smoking.

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