KR20230092710A - Composition comprising a complex comprising a curcuminoid compound, and steviol glycosides or a licorice extract or a fraction thereof, and uses thereof - Google Patents

Abstract

The present invention relates to: a composition containing a complex including a curcuminoid-based compound and a steviol glycoside or a curcuminoid-based compound and a licorice extract or a fraction thereof; and uses for enhancing immunity and/or preventing, improving, or treating COVID-19 according to the activity of immune cells or the increase of the number of cells. The complex according to the present invention includes curcumin and steviol glycosides or a licorice extract or fractions thereof, whose safety has already been confirmed as a food material registered by the Ministry of Food and rated as generally recognized as safe (GRAS) by the US FDA, and suppresses the symptoms of COVID-19 by activating Th1 cells, CD8 T cells, and NK, thereby being provided as food and pharmaceutical compositions for preventing, improving, or treating COVID-19.

Description

Composition comprising a complex comprising a curcuminoid compound, and steviol glycosides or a licorice extract or a fraction thereof, and uses thereof uses it}

The present invention relates to a composition comprising a curcuminoid-based compound and a steviol glycoside, or a complex comprising a curcuminoid-based compound and a licorice extract or a fraction thereof, and immunity enhancement by increasing the activity or cell number of immune cells of the composition, and / or for use in the prevention, amelioration or treatment of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCoV), the cause of the COVID-19 epidemic, was first identified in Wuhan, China in December 2019. Since it first occurred, it has spread to China and around the world. Accordingly, the World Health Organization (WHO) declared COVID-19 a Public Health Emergency of International Concern (PHEIC), and on March 11, 2020, COVID-19 was declared a global epidemic following the Hong Kong flu (1968) and swine flu (2009). It was declared a pandemic. COVID-19 is transmitted when droplets (saliva droplets) from an infected person penetrate the respiratory tract or mucous membranes of the eyes, nose, or mouth. After an incubation period of about 2 to 14 days after infection, respiratory symptoms such as fever, cough, and difficulty breathing or pneumonia appear as the main symptoms, but cases of asymptomatic infection are rare.

Until now, Korea Patent Publication No. 10-2021-0128829 and US Registered Patent US 11191827 B1 have been disclosed as technologies for preventing, improving or treating COVID-19, and other continuous results have been announced, but most of them are effective It is difficult to apply it directly as a therapeutic agent due to safety concerns as well as adverse aspects.

Under this background, turmeric pigment, and steviol glycosides or licorice extracts or fractions thereof, whose safety has already been confirmed as food raw materials registered by the Ministry of Food and Drug Safety in Korea and received a GRAS (Generally Recognized as Safe) rating by the US FDA, The present invention was completed by confirming that the complex activates or increases the number of Th1 cells, CD8 T cells and NK cells to exhibit preventive, ameliorative or therapeutic effects on COVID-19.

One object of the present invention is a curcuminoid-based compound or a pharmaceutically acceptable salt thereof; And steviol glycoside or a pharmaceutically acceptable salt thereof, or licorice extract or a fraction thereof; to provide a pharmaceutical composition for preventing or treating COVID-19, comprising a complex comprising as an active ingredient .

Another object of the present invention is a curcuminoid-based compound or a pharmaceutically acceptable salt thereof; And steviol glycosides or pharmaceutically acceptable salts thereof, or licorice extract or fractions thereof; to provide a composition for enhancing immunity, comprising a complex comprising as an active ingredient.

Another object of the present invention relates to a method for preventing or treating COVID-19, comprising administering the composition of the present invention to a subject.

Another object of the present invention is a curcuminoid-based compound or a food acceptable salt thereof; And to provide a food composition for preventing or improving COVID-19, including a complex comprising a steviol glycoside or a food-acceptable salt thereof, or a licorice extract or a fraction thereof.

Another object of the present invention is a curcuminoid-based compound or a food acceptable salt thereof; And steviol glycosides or food chemically acceptable salts thereof, or licorice extract or fractions thereof; to provide a food composition for enhancing immunity, including a complex comprising.

Each description and embodiment disclosed herein can be applied to each other description and embodiment. That is, all combinations of the various elements disclosed herein fall within the scope of the present invention. In addition, it cannot be seen that the scope of the present invention is limited by the specific descriptions described below.

One aspect of the present invention is a curcuminoid-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof; And steviol glycoside (steviol glycoside) or a pharmaceutically acceptable salt thereof, or licorice extract or fraction thereof; provides a pharmaceutical composition for the prevention or treatment of COVID-19, comprising a complex comprising as an active ingredient.

The curcuminoid-based compound of the present invention may be represented by Formula 1 below.

[Formula 1]

Wherein R ¹ and R ² are each independently hydrogen, a hydroxyl group, or a C ₁ to C ₁₀ alkoxy group, and n and m are 1≤n≤5 and 1≤m≤5.

For example, R ¹ in Formula 1 may be independently of R ² hydrogen, a hydroxyl group, or a C ₁ to C ₁₀ alkoxy group, and R ² independently of R ¹ may be hydrogen, a hydroxyl group, or a C ₁ to C ₁₀ It may be an alkoxy group.

In addition, in R ¹ where n≥2, R ¹ may each independently be hydrogen, a hydroxy group, or a C ₁ to C ₁₀ alkoxy group, and in R ² where n≥2, R ² are each independently hydrogen, a hydroxy group, Or it may be a C ₁ to C ₁₀ alkoxy group.

As another example, the curcuminoid-based compound represented by Chemical Formula 1 of the present invention may be a compound represented by any one selected from Chemical Formulas 2 to 4 below or a mixture thereof, but is not limited thereto.

Formula 2 below is curcumin, Formula 3 below is demethoxycurcumin, which is a natural analogue/congeners of curcumin, and Formula 4 below is bisdemethoxycurcumin, which is a natural analogue of curcumin. can be

As an example of a mixture of compounds represented by any one of Formulas 2 to 4, the combination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin has a total weight of 50 curcumin: demethoxy curcumin: bisdemethoxy curcumin based on 100. to 98:1 to 25:1 to 25 [w/w], 60 to 90:5 to 20:5 to 20 [w/w] or 70 to 80:10 to 15:10 to 15 [w/w] ratio It may be included as, but is not limited thereto.

In the present invention, the curcuminoid-based compound may be mixed with turmeric pigment. In addition, curcumin, demethoxycurcumin, bisdemethoxycurcumin, or a combination thereof may also be mixed with turmeric pigment.

As another example, the curcuminoid compound represented by Formula 1 of the present invention can be obtained by extracting dried rhizomes of turmeric ( Curcuma longa Linne) or turmeric (Turmeric) with ethanol, fat or oil, or an organic solvent (Food and Drug Safety Ministry of Food, Food and Food Additives), but not limited thereto. In this case, the curcuminoid-based compound may be extracted in the form of curcumin, demethoxycurcumin, bisdemethoxycurcumin, or a combination thereof, but is not limited thereto.

In the present invention, the curcuminoid-based compound of the present invention may include not only the curcumin, demethoxycurcumin, and bisdemethoxycurcumin, but also compounds belonging to the curcuminoid-based compound, and the curcumin, demethoxycurcumin, It is apparent to those skilled in the art that derivatives or isomers of bisdemethoxycurcumin may also be used.

As used herein, the term "derivative" refers to a compound obtained by substituting a part of the structure of the compound with another atom or group of atoms.

As used herein, the term "isomer" refers to a compound having the same molecular formula but not the same connection method or spatial arrangement of constituent atoms in a molecule. Isomers include, for example, structural isomers, and stereoisomers.

The above-mentioned curcuminoid-based compounds, analogs, derivatives and isomers thereof may be purchased and used commercially, or extracted and isolated from plants such as turmeric and turmeric that have been collected or cultivated in nature, but are not limited thereto. .

In addition, the present invention may use a plant extract containing a curcuminoid-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof, and for example, a turmeric extract or a turmeric extract may be used, but is not limited thereto. .

In the present invention, turmeric extract, turmeric extract, turmeric or turmeric may be purchased and used commercially, or collected or cultivated in nature, but is not limited thereto.

As used herein, the term "steviol glycoside" refers to a natural polysaccharide material derived from Stevia rebaudiana Bertoni and having a sugar content 300 times that of sugar. The steviol glycosides are composed of various sugars such as steviol glycosides A1, A2, steviol 1, 2, 3, dulcoside, and rebaudioside a, b, c, e, and f.

In the present invention, the steviol glycoside may be preferably derived from stevia ( Stevia rebaudiana Bertoni ).

For example, the steviol glycoside may be obtained from the leaf portion of Stevia, but is not limited thereto.

As another example, steviol glycosides can be obtained by extracting dried leaves of stevia with hot water, concentrating the water-soluble extract obtained by treating it with an adsorbent resin, going through purification such as recrystallization using methanol or ethanol, and then drying ( Ministry of Food and Drug Safety, Food and Food Additives Code), but not limited thereto.

In addition, the present invention may use a plant extract containing steviol glycosides, for example, a stevia extract or the like, but is not limited thereto.

In the present invention, the steviol glycoside, stevia extract, or stevia may be purchased and used commercially, or collected or cultivated in nature, but is not limited thereto.

In the present invention, the term "licorice" is a perennial herbaceous plant belonging to the leguminous family, and is native to or cultivated in northern China, Siberia, southern Italy, Manchuria, Mongolia, Uzbekistan, and the like. The licorice may be, for example, Glycyrrhiza inflata BATALIN, Glycyrrhiza uralensis FISCHER, and Glycyrrhiza glabra LINNE, but is not limited thereto.

In the present invention, the term "extract" refers to an extract obtained by extracting the licorice, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a crude or purified product of the extract, or a mixture thereof, etc. and extracts of all formulations that can be formed using the extract solution.

As a method for preparing the licorice extract, conventional extraction methods in the art such as ultrasonic extraction, filtration and reflux extraction may be used. Preferably, it may be an extract obtained by pulverizing licorice from which foreign substances have been removed by washing and drying, extracted with water, alcohol having 1 to 4 carbon atoms (C1 to C4), or a mixed solvent thereof, more preferably C1 to C4. It may be an extract extracted with C4 alcohol, and most preferably an extract extracted with methanol or ethanol. At this time, the extraction solvent is preferably 2 to 20 times the dry weight of licorice. For example, after cutting the dried licorice, put it in an extraction container, add C1-C4 lower alcohol or a mixed solvent thereof, preferably methanol or ethanol, leave it at room temperature for a certain period of time, and then filter to obtain an alcohol extract. At this time, it is preferable to leave the extraction at room temperature for 1 week, after which it may be additionally subjected to a method such as concentration or lyophilization, but is not limited thereto. Alternatively, a commercially available licorice extract may be purchased and used.

As used herein, the term "fraction" refers to a product obtained by a fractionation method for separating a specific component or a specific group from a mixture containing various components. The licorice fraction, for example, can be obtained by suspending the licorice extract in water and then fractionating using a non-polar solvent such as hexane or ethyl acetate to obtain a polar solvent fraction and a non-polar solvent fraction, respectively. Specifically, after suspending the crude licorice extract in distilled water, about 1 to 100 times, preferably about 1 to 5 times the volume of a non-polar solvent such as hexane and ethyl acetate is added 1 to 10 times, preferably about 1 to 5 times the volume of the suspension. It may be obtained by extracting and separating the non-polar solvent-soluble layer 2 to 5 times, but is not limited thereto. In addition, a conventional fractionation process may be performed (Harborne J.B. Phytochemical methods: A guide to modern techniques of plant analysis, 3rd Ed. p6-7, 1998).

For example, the complex of the present invention may include i) a curcuminoid-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof; and steviol glycosides or pharmaceutically acceptable salts thereof; or ii) a curcuminoid-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof; And licorice extract or a fraction thereof; may be one containing. However, a plant extract containing the curcuminoid-based compound or a pharmaceutically acceptable salt thereof, or a fraction thereof; It does not exclude plant extracts containing steviol glycosides or pharmaceutically acceptable salts thereof, or fractions thereof.

That is, the complex of the present invention includes i) a curcuminoid-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof, a plant extract containing the same, or a fraction thereof; and steviol glycosides or pharmaceutically acceptable salts thereof, plant extracts containing the same, or fractions thereof; or ii) a curcuminoid-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof, a plant extract containing the same, or a fraction thereof; And licorice extract or a fraction thereof; may be one containing.

As another example, in the complex of the present invention, the ratio of the curcuminoid-based compound represented by Formula 1 and the steviol glycoside or licorice extract can be arbitrarily selected by those skilled in the art, for example, the mixing ratio thereof can be arbitrarily selected, and the total weight Based on 100, steviol glycoside: curcuminoid compound or licorice extract: curcuminoid compound 90 to 99.9: 0.1 to 10 [w/w], 92 to 99.8: 0.2 to 8 [w/w], 94 to 99.7: 0.3 to 6 [w/w], 96 to 99.6: 0.4 to 4 [w/w], 98 to 99.6: 0.4 to 2 [w/w] or 98.5 to 99.6: 0.4 to 1.5 [w/w] It may be included in a ratio, but is not limited thereto.

Specifically, in the complex of the present invention, based on the total weight of 100, steviol glycosides: curcuminoid compounds are 90 to 99.9: 0.1 to 10 [w/w], 92 to 99.7: 0.3 to 8 [w/w], 94 to 99.5: 0.5 to 6 [w/w], 96 to 99.3: 0.7 to 4 [w/w], 98 to 99.1: 0.9 to 2 [w/w], or 98.5 to 99: 1 to 1.5 [w/w] ] may be included in the ratio, but is not limited thereto.

Alternatively, in the complex of the present invention, based on the total weight of 100, licorice extract: curcuminoid compounds are 90 to 99.9: 0.1 to 10 [w/w], 92 to 99.8: 0.2 to 8 [w/w], 94 to 94 99.7: 0.3 to 6 [w/w], 96 to 99.6: 0.4 to 4 [w/w], 98 to 99.6: 0.4 to 2 [w/w], or 99 to 99.6: 0.4 to 1 [w/w] ratio It may be included as, but is not limited thereto.

The composition of the present invention may have a preventive or therapeutic effect on COVID-19.

In the present invention, the term "coronavirus infection-19 (COVID-19)" is caused by type 2 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCoV) infection It is a disease that is transmitted when droplets (saliva droplets) of an infected person penetrate the respiratory tract or mucous membranes of the eyes, nose, or mouth. After an incubation period of about 2 to 14 days after infection, respiratory symptoms such as fever, cough, and difficulty breathing or pneumonia appear as the main symptoms, but cases of asymptomatic infection are rare.

In the present invention, the term "prevention" means any action that suppresses or delays the onset of COVID-19 by administration of the composition.

In the present invention, the term "treatment" refers to all activities that improve or beneficially change the symptoms caused by COVID-19 by the administration of the composition.

In one embodiment of the present invention, as a result of confirming the lung lesion improvement rate of curcumin and steviol glycoside complex (TSP) in the COVID-19 animal model, the VC group infected with SARS-CoV-2 (severe infection model, 62% lung lesion , lung lesion improvement rate of 1%) compared to TSP (curcumin content 8.9 mg/kg/day) or TSP (curcumin content 25 mg/kg/day) administered for 4 consecutive days (TSP 78 or TSP-218.75, respectively) The rate of improvement of lung lesions was 14.9% and 31.2% without any findings, confirming that the lung lesions were significantly improved (FIG. 13). However, in the result of administering the complex (TSP-C 78; TSP: poorly water-soluble curcumin = 9:1 [w/w]) (curcumin content 8.9 mg/kg/day) under the same conditions, further comprising poorly water-soluble curcumin, The efficacy was significantly lowered, showing a 6.1% improvement in lung lesions.

In addition, as a result of confirming the rate of improvement in lung lesions of curcumin and licorice extract complex (TGP), compared to the VC group infected with SARS-CoV-2, the TGP group (TGP group administered with TGP (curcumin content of 3.0 mg mg/kg/day) for 4 consecutive days) 78), the rate of improvement in lung lesions was 20.2% without abnormal findings, confirming that there was significant improvement (FIG. 14). However, the result of administering the complex additionally containing poorly water-soluble curcumin (TGP-C 78; TGP: poorly water-soluble curcumin = 9:1 [w/w]) (curcumin content 3.0 mg/kg/day) under the same conditions was also The efficacy was significantly lowered, showing a 15.3% improvement in lung lesions.

That is, the prevention or treatment effect of COVID-19 of the complex of the present invention described above may be achieved by water-solubilization of curcumin.

In order for a functional substance to exhibit efficacy in the body, it is essential that absorption occurs in the blood and maintains persistence for a certain period of time. Therefore, in one embodiment of the present invention, in order to water-solubilize curcumin, a functional poorly soluble substance, steviol glycoside or licorice extract was mixed with curcumin, and a microwave agitation extractor (Korean Patent No. 10) was used to prepare a water-soluble complex of curcumin. -1436464) was used.

In the present invention, the term "water solubilization" means a phenomenon in which the solubility of a substance that is poorly soluble in water increases due to the presence of a substance such as a surfactant. As a method for water-solubilization, a method of solubilizing useful vitamins or hormones to be water-soluble or promoting emulsion polymerization is widely applied. In the present invention, steviol glycosides or licorice extracts are used as a water-soluble agent, and the steviol glycosides or licorice extracts of the present invention are mixed with curcumin, a poorly soluble substance, so that curcumin has a water (or blood) water-soluble structure. A sanctification complex can be formed.

In particular, curcumin, steviol glycosides and/or licorice extract constituting the active ingredient complex of the present invention are listed in the Ministry of Food and Drug Safety in Korea and are safe as food ingredients that have received a GRAS (Generally Recognized as Safe) rating from the US FDA. has already been confirmed

Thus, the composition comprising the complex of the present invention can be provided as a pharmaceutical composition having a use for preventing or treating COVID-19 without safety concerns.

The pharmaceutical composition of the present invention may further include suitable carriers, excipients or diluents commonly used in the preparation of pharmaceutical compositions. At this time, the content of the complex as an active ingredient included in the pharmaceutical composition is not particularly limited thereto, but may include 0.0001% to 10% by weight, preferably 0.001% to 1% by weight, based on the total weight of the composition. there is.

The pharmaceutical composition may have any formulation selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solvents, freeze-dried formulations, and suppositories. It can be oral or parenteral in various dosage forms. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient, for example, starch, calcium carbonate, sucrose or lactose ( lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used.

The composition of the present invention may be for oral administration, but is not limited thereto.

The composition of the present invention can be administered in a pharmaceutically effective amount.

As used herein, the term "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 is dependent on the type and severity of the subject, age, sex, and disease. It may be determined according to factors including type, activity of drug, sensitivity to drug, administration time, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field. The composition of 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 it can be single or multiple administrations. It is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all the above factors, and can be easily determined by those skilled in the art. The preferred dosage of the composition of the present invention varies depending on the condition and weight of the patient, the severity of the disease, the drug form, the route of administration and the period, but for a desired effect, the composition of the present invention is preferably 0.0001 to 500 mg / kg per day. Preferably, it may be administered at 0.001 to 250 mg/kg, and for example, curcumin in the composition of the present invention may be administered at 25 mg/kg or more per day. Administration may be administered once a day, or may be administered in several divided doses. The composition can be administered to various mammals such as rats, livestock, and humans by various routes, and the method of administration includes without limitation as long as it is a conventional method in the art, for example, oral, rectal or intravenous, intramuscular, It may be administered by subcutaneous, intrauterine, or intracerebrovascular injection. Specifically, the composition of the present invention may be for oral administration, but is not limited thereto.

In addition, the pharmaceutical composition of the present invention can be used in the form of animal medicine as well as medicine applied to humans. Here, the animal is a concept including livestock and companion animals.

In the present invention, the pharmaceutical composition may include a salt, particularly in the form of a pharmaceutically acceptable salt. As the salt, a salt commonly used in the art, such as an acid addition salt formed by a pharmaceutically acceptable free acid, may be used without limitation.

In the present invention, the term "pharmaceutically acceptable salt" is a concentration that has a relatively non-toxic and harmless effect on the subject, and any of the above compositions that do not reduce the beneficial effects of the composition of the present invention due to side effects caused by the salt. means an organic or inorganic addition salt.

Acid addition salts are prepared by conventional methods, for example, by dissolving a compound in an excess of an aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Equimolar amounts of the compound and an acid or alcohol (eg, glycol monomethyl ether) in water may be heated, and then the mixture may be evaporated to dryness, or the precipitated salt may be suction filtered.

At this time, organic acids and inorganic acids can be used as the free acid, and hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. can be used as the inorganic acid, and methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and maleic acid can be used as the organic acid. (maleic acid), succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid (gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc. can be used. , but not limited to these.

In addition, a pharmaceutically acceptable metal salt may be prepared using a base. The alkali metal salt or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable for preparing a sodium, potassium, or calcium salt, but is not limited thereto. In addition, the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

Pharmaceutically acceptable salts of the present invention, unless otherwise indicated, include salts of acidic or basic groups that may be present in the compositions of the present invention. For example, pharmaceutically acceptable salts may include sodium, calcium, and potassium salts of a hydroxy group, and other pharmaceutically acceptable salts of an amino group include hydrobromide, sulfate, hydrogen sulfate, phosphate, and hydrogen phosphate. , dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, etc., preparation of salts known in the art It can be produced through the method.

Another aspect of the present invention is a curcuminoid-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof; And steviol glycosides or pharmaceutically acceptable salts thereof, or licorice extract or fractions thereof; provides a composition for enhancing immunity comprising a complex as an active ingredient.

Curcuminoid compounds represented by Formula 1, steviol glycosides, pharmaceutically acceptable salts, licorice extracts and fractions are as described above.

In the present invention, the curcuminoid-based compound represented by Chemical Formula 1 may be a compound represented by any one selected from Chemical Formulas 2 to 4, or a mixture thereof, as described above.

In the present invention, the steviol glycoside may be derived from stevia ( Stevia rebaudiana Bertoni ), but is not limited thereto, as described above.

In the present invention, the licorice may be Glycyrrhiza inflata BATALIN, Glycyrrhiza uralensis FISCHER or Glycyrrhiza glabra LINNE, but is not limited thereto, as described above.

The composition of the present invention may have an immune enhancing effect.

In the present invention, the term "immunity enhancement" means to enhance the activity of a series of in vivo immune responses to protect the body from antigens, which are external substances such as bacteria, viruses, cancer cells, blood and tissues of other people or animals. .

For example, the immunity enhancement may be the activation and/or cell number enhancement of immune cells, and for example, the immunity enhancement may be the activation and/or cell number enhancement of Th1 cells, CD8 T cells and/or NK cells. , but not limited thereto.

In the present invention, the Th1 cell may be a multifunctional Th1 cell that simultaneously induces IFN-gamma, TNF-alpha and IL-2, for example, simultaneously induces IFN-gamma, TNF-alpha and IL-2 CD3 ⁺ It may be CD4 ⁺ cells, but is not limited thereto.

The CD8 T cells may be multifunctional CD8 ⁺ T cells that simultaneously induce IFN-gamma, TNF-alpha and IL-2, for example, CD3 ⁺ CD8 + simultaneously induce IFN-gamma, TNF-alpha and IL-2 ^. It may be a cell, but is not limited thereto.

The NK cells may be activated NK cells, for example, IFN- IFN-gamma ⁺ CD107a ⁺ Granzyme B ⁺ NK cells, but are not limited thereto.

In one embodiment of the present invention, curcumin and steviol glycoside complex (TSP) or curcumin and licorice extract complex (TGP) was administered in an immunocompromised animal model in which immune decline was induced by cyclophosphamide (CTX) administration. As a result, the number of CD4 ⁺ and CD8 ⁺ T cells reduced by CTX (Figs. 3-4), the ratio of Th1 and activated CD8 ⁺ T cells (Figs. 5-6), the ratio of multifunctional Th1 or CD8 ⁺ T cells ( 7-8), and the number of activated NK cells (FIGS. 9-10) was confirmed to be restored.

That is, the preventive or therapeutic effect of the complex of the present invention described above on COVID-19 may be achieved by an immune enhancing effect by activating Th1 cells, CD8 T cells, and NK by water-solubilization of curcumin.

In the present invention, the composition of the present invention may be for oral administration, but is not limited thereto.

Another aspect of the present invention is a) a first composition comprising a curcuminoid-based compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient; and mixing a second composition comprising a steviol glycoside or a pharmaceutically acceptable salt thereof, or a licorice extract or a fraction thereof as an active ingredient; And b) providing a method for producing a pharmaceutical composition for preventing or treating COVID-19, comprising the step of treating the mixture with microwaves.

Curcuminoid compounds represented by Formula 1, steviol glycosides, pharmaceutically acceptable salts, licorice extracts and fractions, and COVID-19 are as described above.

In the present invention, the term "microwave" is an AC signal with a frequency band between 300 MHz and 300 GHz or a wavelength between 1 m and 1 mm.

The method of treating the microwave is not limited thereto, but in a microwave stirring extractor (Korean Patent Registration No. 10-1436464), 10 to 200 minutes at 1,000 to 24,000 W, 20 to 160 minutes at 3,000 to 22,000 W, 5,000 It may be stirring extraction for 30 to 120 minutes at 20,000 W, 40 to 100 minutes at 7,000 to 18,000 W, or 40 to 80 minutes at 10,000 to 15,000 W.

In addition, after the extraction is completed, a step of purifying with filter paper may be further included, but is not limited thereto.

Another aspect of the present invention provides a method for preventing or treating COVID-19, comprising administering the composition of the present invention to a subject.

Curcuminoid compounds represented by Formula 1, steviol glycosides, pharmaceutically acceptable salts, licorice extracts and fractions, and COVID-19 are as described above.

In the present invention, the term "subject" refers to all animals other than humans that have or may have COVID-19, and by administering the pharmaceutical composition of the present invention to a subject suspected of COVID-19, the subject can be effectively treated. can

As used herein, the term "administration" means introducing the pharmaceutical composition of the present invention to a subject suspected of COVID-19 by any suitable method. The administration route may be administered through various oral or parenteral routes as long as it can reach the target tissue, as described above.

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount, as described above.

The pharmaceutical composition of the present invention is not particularly limited as long as it is an object for the prevention or treatment of COVID-19, and is applicable to any object. For example, non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cows, sheep, pigs, goats, birds, and fish may be used, and the pharmaceutical composition may be used parenterally, subcutaneously, It can be administered intraperitoneally, intrapulmonaryly and intranasally, and for local treatment, it can be administered by any suitable method, including intralesional administration if necessary. The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and body weight of the subject, the severity of the disease, the drug type, the route and duration of administration, but can be appropriately selected by those skilled in the art. For example, it may be administered by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine intrathecal or intracerebrovascular injection, but is not limited thereto.

In the present invention, the administration may be oral administration, but is not limited thereto.

Another aspect of the present invention relates to a curcuminoid-based compound represented by Formula 1 or a food-acceptable salt thereof; And steviol glycosides or food-acceptable salts thereof, or licorice extract or fractions thereof; It provides a food composition for preventing or improving COVID-19, including a complex comprising a.

Another aspect of the present invention relates to a curcuminoid-based compound represented by Formula 1 or a food-acceptable salt thereof; And steviol glycosides or food chemically acceptable salts thereof, or licorice extract or fractions thereof; It provides a food composition for enhancing immunity, comprising a complex comprising as an active ingredient.

Curcuminoid compounds represented by Formula 1, steviol glycosides, pharmaceutically acceptable salts, licorice extracts and fractions, and COVID-19 are as described above.

In the present invention, the curcuminoid-based compound represented by Chemical Formula 1 may be a compound represented by any one selected from Chemical Formulas 2 to 4, or a mixture thereof, as described above.

In the present invention, the steviol glycoside may be derived from stevia ( Stevia rebaudiana Bertoni ), but is not limited thereto, as described above.

In the present invention, the licorice may be Glycyrrhiza inflata BATALIN, Glycyrrhiza uralensis FISCHER or Glycyrrhiza glabra LINNE, but is not limited thereto, as described above.

The food composition of the present invention may have an effect of preventing or improving COVID-19 and/or enhancing immunity, as described above.

In the present invention, the term "improvement" refers to all activities that improve or benefit the symptoms of suspected or affected individuals of COVID-19 by using the composition.

The food composition of the present invention includes forms such as pills, powders, granules, precipitates, tablets, capsules or liquids, and the food to which the composition can be added includes, for example, various foods, such as beverages, There are chewing gum, tea, vitamin complexes, and health supplements.

Ingredients that can be included in the food composition of the present invention are not particularly limited to other ingredients other than containing active ingredients as essential ingredients, and, like conventional foods, various herbal extracts, food supplement additives, or natural carbohydrates as additional ingredients. may contain The content of the active ingredient in the food composition may be appropriately determined depending on the purpose of use (prevention, improvement or therapeutic treatment). At this time, the content of the active ingredient included in the composition is not particularly limited thereto, but may include 0.0001% to 10% by weight, specifically 0.001% to 1% by weight based on the total weight of the composition.

In addition, the food auxiliary additives may include food auxiliary additives common in the art, for example, flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like.

Examples of the natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. In addition to the above, natural flavors (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can advantageously be used as flavoring agents.

In addition to the above, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like may be contained. In addition, it may contain fruit flesh for the production of natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination.

In the present invention, the health supplement may include health functional food and health food.

The health functional food (functional food) is the same term as food for special health use (FoSHU), and has high medical effect and is processed to efficiently display bioregulatory functions in addition to nutrient supply. means food. Here, "function (sex)" means obtaining useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions.

Food containing the food composition of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components commonly added in the art during the preparation. In addition, the formulation of the food may also be prepared without limitation as long as the formulation is recognized as a food. The food composition of the present invention can be prepared in various types of formulations, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time by using food as a raw material, and has excellent portability.

The food composition of the present invention may include a salt, particularly a food pharmaceutically acceptable salt form, and the definition and details thereof are the same as those described for the pharmaceutically acceptable salt.

In particular, as described above, curcumin, steviol glycosides and/or licorice extract constituting the active ingredient complex of the present invention are food ingredients registered in the Ministry of Food and Drug Safety and received the US FDA GRAS grade, without safety concerns. It can be provided as a food composition having a use for preventing or improving COVID-19.

According to the present invention, the complex comprising curcumin, which has already been confirmed to be stable as a food material registered by the Ministry of Food and Drug Safety and received the US FDA GRAS (Generally Recognized as Safe) grade, and steviol glycosides or licorice extracts or fractions thereof, is a Th1 cell , By activating CD8 T cells and NK to suppress the symptoms of COVID-19, it can be provided as a food and pharmaceutical composition for preventing, improving or treating COVID-19.

1 is a diagram showing a water-soluble curcumin and steviol glycoside complex (Tencumin S plus; TSP), curcumin, a water-soluble curcumin and licorice extract complex (Tencumin G plus; TGP) before vacuum freeze-drying.
Figure 2 is a schematic diagram of an experiment using an immunocompromised animal model.
3 is a result confirming the CD4 ⁺ and CD8 ⁺ T cell recovery ability by TSP administration in an immunocompromised animal model.
4 is a result confirming the CD4 ⁺ and CD8 ⁺ T cell recovery ability by TGP administration in an immunocompromised animal model.
5 is a result of confirming the ability to recover Th1 and activated CD8 ⁺ T cells by TSP administration in an immunocompromised animal model.
6 is a result of confirming the ability to recover Th1 and activated CD8 ⁺ T cells by TGP administration in an immunocompromised animal model.
Figure 7 is a result confirming the multifunctional Th1 or multifunctional CD8 ⁺ T cell recovery ability by TSP administration in an immunocompromised animal model.
8 is a result of confirming the ability to recover multifunctional Th1 or multifunctional CD8 ⁺ T cells by TGP administration in an immunocompromised animal model.
9 is a result confirming the recovery ability of activated NK cells by TSP administration in an immunocompromised animal model.
10 is a result confirming the recovery ability of activated NK cells by TGP administration in an immunocompromised animal model.
11 is a diagram showing lung tissue collected through autopsy for each test group for TSP administration.
12 is a diagram showing lung tissue collected through autopsy for each test group for TGP administration.
13 is a diagram showing the macroscopic lung lesion healing rate according to TSP administration. Abbreviations: NC (Negative control), VC (Virus control) and PC (Positive control).
14 is a diagram showing the macroscopic lung lesion healing rate according to TGP administration. Abbreviations: NC (Negative control), VC (Virus control) and PC (Positive control).

Hereinafter, the present invention will be described in more detail through the following examples. However, these examples are intended to illustrate the present invention by way of example, and the scope of the present invention is not limited only to these examples.

Example 1: Composite Preparation

To prepare a water-soluble curcumin and steviol glycoside complex (hereinafter referred to as Tencumin S plus; TSP), 200 g of steviol glycoside was dissolved in 1 L of water (concentration: 20% [v/v]), followed by purity 9 g of about 95% or more Indian turmeric pigment (curcumin: demethoxycurcumin: bisdemethoxycurcumin = 75: 15: 10 [w/w]) was added and mixed. When turmeric pigment was mixed with the steviol glycoside aqueous solution, 30 to 35% of turmeric pigment was dissolved. After purification, it was vacuum-lyophilized to obtain TSP powder.

The TSP contained 200 g or less of steviol glycosides and 3.0 g or more of turmeric pigment per 203 g of total powder weight.

To prepare a water-soluble curcumin and licorice extract complex (hereinafter referred to as Tencumin G plus; TGP), 200 g of licorice extract (Dodam Herb, Korea; Uzbekistan) was dissolved in 1 L of water (concentration 20% [v /v]), 3 g of Indian turmeric pigment (curcumin: demethoxycurcumin: bisdemethoxycurcumin = 75: 15: 10 [w/w]) having a purity of about 95% or higher was mixed. When turmeric pigment was mixed with the aqueous solution of licorice extract, 30 to 35% of turmeric pigment was dissolved, and the dissolved mixture was put into a microwave stirring extractor (Korean Patent No. 10-1436464), stirred and extracted at 12,000 W for 60 minutes, and filtered with filter paper. After purification, vacuum lyophilization was performed to obtain TGP powder.

The TGP contained less than 200 g of licorice extract and more than 1.0 g of turmeric pigment per 201 g of total powder weight.

TSP, curcumin and TGP before vacuum freeze drying are as shown in FIG. 1.

Example 2: Evaluation of immune cell recovery ability of complexes in immunocompromised animal models

2-1. CD4 ⁺ and CD8 ⁺ Confirmation of T cell recovery ability

3 days after oral administration of TSP (50 and 100 mg/kg) or TGP (10 and 50 mg/kg) prepared in Example 1 to mice once a day for a total of 5 times, the number of T cells in the spleen was measured. Cyclophosphamide (CTX), an immunosuppressant that rapidly decreases, was intraperitoneally injected once a day for a total of 5 times (FIG. 2). 3 days after CTX injection, splenocytes from mice were isolated and treated with T cell activators (PMA/Ino; Phorbol 12-myristate 13-acetate; PMA), ionomycin , including Brefeldin A, Monensin and protein transport inhibitors) for 4 hours.

To measure the number of T cells, splenocytes were treated with Live/dead cell staining reagent, anti-CD3, anti-CD4 and anti-CD8 antibodies, allowed to stand at room temperature for 20 minutes, and then stained in PBS (Phosphate-buffered saline). After washing several times with , it was analyzed by flow cytometry.

As a result, when 100 mg/kg of TSP was administered 5 times before CTX treatment, it was confirmed that the number of CD4 ⁺ and CD8 ⁺ T cells decreased by CTX was recovered (FIG. 3).

In addition, when 10 or 50 mg/kg of TGP was administered 5 times before CTX treatment, it was confirmed that the number of CD4 ⁺ and CD8 ⁺ T cells reduced by CTX was recovered (FIG. 4).

2-2. Th1 and activating CD8 ⁺ Confirmation of T cell recovery ability

In order to measure the number of Th1 or activated CD8 ⁺ T cells according to the administration of the complex (TSP or TGP) of Example 1 in the same animal model as in Example 2-1, splenocytes were treated with PMA/Ino for 4 hours Then, Live/dead cell staining reagent, anti-CD3, anti-CD4, anti-CD8 and anti-CD25 antibodies were treated, left at room temperature for 20 minutes, stained, and washed several times with PBS. After fixing the cell surface using the Fix & Perm Cell permeabilization kit and making holes at the same time, anti-IFN-gamma, anti-IL-5, anti-IL-17A and anti-Foxp3 antibodies were used at room temperature for 20 minutes. After being left to stain, it was analyzed by flow cytometry.

As a result, when CTX was injected intraperitoneally, Th1 (IFN-gamma ⁺ CD3 ⁺ CD4 ⁺ cells), Th2 (IL-5 ⁺ CD3 ⁺ CD4 ⁺ cells), Th17 (IL-17A ⁺ CD3 ⁺ CD4 ⁺ cells), and regulatory T Cells (Foxp3 ⁺ CD25 ⁺ CD3 ⁺ CD4 ⁺ cells) and activated CD8 ⁺ T cells (IFN-gamma ⁺ CD3 ⁺ CD8 ⁺ cells) were both reduced, but when 100 mg/kg of TSP was administered 5 times before CTX treatment, CTX It was confirmed that the decreased ratio of Th1 and activated CD8 ⁺ T cells was restored (FIG. 5).

In addition, when 10 or 50 mg/kg of TGP was administered 5 times before CTX treatment, it was confirmed that the ratio of Th1 and activated CD8 ⁺ T cells decreased by CTX was restored (FIG. 6).

2-3. Multifunctional Th1 and multifunctional CD8 ⁺ Confirmation of T cell recovery ability

CD4 ⁺ or CD8 ⁺ T cells simultaneously induce the Th1 cytokines IFN-gamma, TNF-alpha and IL-2, and are therefore also referred to as multifunctional T cells (multifunctional Th1 or multifunctional CD8 ⁺ T cells, respectively).

In order to measure the number of multifunctional T cells according to the administration of the complex (TSP or TGP) of Example 1 in the same animal model as in Example 2-1, splenocytes were treated with PMA/Ino for 4 hours and Live/ The cells were treated with dead cell staining reagent, anti-CD3, anti-CD4 and anti-CD8 antibodies, allowed to stand at room temperature for 20 minutes, stained, and then washed several times with PBS. After fixing the cell surface using the Fix & Perm Cell permeabilization kit and making a hole at the same time, using anti-IFN-gamma, anti-TNF-alpha, and anti-IL-2 antibodies, the cell surface was left at room temperature for 20 minutes and stained. and then analyzed by flow cytometry.

As a result, multifunctional Th1 cells (IFN-gamma, TNF-alpha, and IL-2 co-induced CD3 ⁺ CD4 ^{+ cells) and multifunctional CD8 + T cells (IFN-gamma, TNF-alpha, and IL-2 co-induced CD3 + CD4 +} cells) and multifunctional CD8 ⁺ T cells (IFN-gamma, TNF-alpha, and IL-2) were observed when CTX was injected intraperitoneally. -2 co-induced CD3 ⁺ CD8 ⁺ cells) were all reduced, but when 100 mg/kg of TSP was administered 5 times before CTX treatment, it was confirmed that the ratio of multifunctional Th1 or CD8 ⁺ T cells reduced by CTX was restored (Fig. 7).

In addition, when 50 mg/kg of TGP was administered 5 times before CTX treatment, it was confirmed that the ratio of multifunctional Th1 or CD8 ⁺ T cells decreased by CTX was restored (FIG. 8).

2-4. Confirmation of NK cell recovery ability

In order to measure the number of activated NK cells according to the administration of the complex (TSP or TGP) of Example 1 in the same animal model as in Example 2-1, splenocytes were treated with PMA/Ino for 4 hours and Live/dead Cell staining reagent, lineage antibodies (anti-CD19, anti-CD14, and anti-CD3e) and anti-NK1.1 antibody were treated, left at room temperature for 20 minutes, stained, and then washed several times with PBS. After fixing the cell surface using the Fix & Perm Cell permeabilization kit, a hole was made at the same time, and then stained by using anti-IFN-gamma, anti-CD107a and anti-Granzyme B antibodies at room temperature for 20 minutes, followed by flow cytometry. was analyzed.

As a result, when TSP (50 or 100 mg/kg) was administered 5 times before CTX treatment, it was confirmed that the number of activated NK cells (IFN-gamma ⁺ CD107a ⁺ Granzyme B ⁺ NK cells) decreased by CTX was restored ( Fig. 9).

also, When TGP (10 or 50 mg/kg) was administered 5 times before CTX treatment, it was confirmed that the number of activated NK cells decreased by CTX was restored (FIG. 10).

According to the above results, it was confirmed that both TSP and TGP had an effect of restoring multifunctional Th1, multifunctional CD8 ⁺ T cells, and activated NK cells, which were reduced by immunosuppressive agents.

Example 3: Evaluation of drug efficacy in COVID-19 animal model

The composite of Example 1 using a Syrian Hamster animal model infected with type 2 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and exhibiting COVID-19 symptoms The therapeutic effect of (TSP or TGP) on COVID-19 was confirmed.

The animal model was produced by administering COVID-19 according to the method in Table 1 below, and the negative control group (NC), the positive control virus group (VC), and the test group administered with TSP were divided as shown in Table 2 below.

Specifically, respiratory anesthesia was performed for 10 minutes using isoflurane, and 100 μL of the prepared SARS-CoV-2 virus was instilled into the nasal cavity of the hamster to infect it, and then the drug was administered orally for each test group according to Table 2 below. It was orally administered (P.O) at 10 mL/kg using a zone belt.

Hamsters Female, 5n/groups Age 11 weeks old Virus Titer 2.0×10 ⁵ PFU/mL Inoculate Route Intranasal (100 μL) Drug Administration per oral (PO, 10 mL/kg)

Test group No. Group (n=5) Dose
(mg/head) Vehicle/Volume
(mL/kg) Route/Interval
(h) note One Negative control (NC) 0 Water / 10 P.O/(24 h/total 4 times) - 2 Virus control (VC) 0 Water / 10 P.O/(24 h/total 4 times) - 3 TSP 218.75 Water / 10
(acceptable) Simultaneous administration after PO/infection
(24 h/4 times in total) Curcumin content 25 mg/kg/day 4 TSP 39 Water / 10
(acceptable) Simultaneous administration after PO/infection
(24 h/8 times in total) Curcumin content 8.9 mg/kg/day 5 TSP:Curcumin = 9 : 1 39 Water / 10 (water soluble) Simultaneous administration after PO/infection
(24 h/8 times in total) Curcumin content 8.9 mg/kg/day 6 TGP 39 Water / 10 (water soluble) Simultaneous administration after PO/infection
(24 h/8 times in total) Curcumin content 3.0 mg/kg/day 7 TGP:Curcumin = 9 : 1 39 Water / 10 (water soluble) Simultaneous administration after PO/infection
(24 h/8 times in total) Curcumin content 3.0 mg/kg/day

On the 4th day after infection (PID4), macroscopic lung lesions were evaluated for lung tissues (FIG. 11 and FIG. 12) collected through autopsy for each test group.

Specifically, as shown in Table 3 below, it was divided into ① to ⑤ according to the lung lobe, and the lung lesion improvement rate was visually evaluated according to each weight, and the lung lesion healing rate was calculated by substituting it into the following formula.

Gross lung lesion cure rate = Pneumonia induction rate in TSP group / Pneumonia induction rate in VC group × 100

Lung lobe % of lung weight (%) ① 40 ② 10 ③ 5 ④ 30 ⑤ 15 Total area % 100

As a result, water-soluble TSP (78 mg/head/day, curcumin content 8.9 mg/kg/day; table Test group 4 of 2) or TSP group administered with water-soluble TSP (218.75 mg/head/day, curcumin content 25 mg/kg/day; Test group 3 in Table 2) for 4 consecutive days (TSP 78 or TSP-218.75, respectively) , the rate of improvement of lung lesions was 14.9% and 31.2%, respectively, without abnormal findings, indicating that lung lesions were significantly improved. However, a complex further comprising poorly water-soluble curcumin (TSP-C 78; TSP: poorly water-soluble curcumin = 9: 1 [w/w]) (78 mg/head/day, curcumin content 8.9 mg/kg/day; table As a result of administering test group 5) of 2 under the same conditions, the efficacy was significantly lowered, confirming a 6.1% improvement rate of lung lesions (FIG. 13).

In addition, in the TGP group (TGP 78) administered with water-soluble TGP (78 mg/head/day, curcumin content 3.0 mg mg/kg/day; test group 6 in Table 2) for 4 consecutive days under the same conditions, there were no abnormalities in lung lesions. The improvement rate was 20.2%, showing significant improvement. However, a complex additionally containing poorly water-soluble curcumin (TGP-C 78; TGP: poorly water-soluble curcumin = 9: 1 [w/w]) (78 mg/head/day, curcumin content 3.0 mg/kg/day; table As a result of administering test group 7) of 2 under the same conditions, the efficacy was also significantly lowered, confirming a pulmonary lesion improvement rate of 15.3% (FIG. 14).

In particular, TSP showed excellent improvement effects on bilateral pneumonia, pulmonary edema, and pulmonary hemorrhage caused by SARS-CoV-2 infection.

According to the above results, when poorly water-soluble curcumin was additionally added to the complex (TSP or TGP) of Example 1 and orally administered, it was confirmed that the efficacy of improving lung lesions was significantly lowered.

From the results of the above examples, the soluble curcumin and steviol glycoside complex (TSP) or the soluble curcumin and licorice extract complex (TGP) of the present invention has a multifunctional Th1, multifunctional CD8 ⁺ T cell and activated NK activity and cell number It was confirmed that it exhibits the effect of significantly improving pulmonary lesions caused by SARS-CoV-2 infection.

In particular, curcumin and steviol glycosides constituting TSP, as well as licorice extract constituting TGP, are listed in the Ministry of Food and Drug Safety in Korea and have received a GRAS (Generally Recognized as Safe) rating from the US FDA, and their safety has already been confirmed. Bar, it can be provided as a food and pharmaceutical composition for the prevention, improvement or treatment of COVID-19.

From the above description, those skilled in the art to which the present invention pertains will be able to understand that the present invention may be embodied in other specific forms without changing its technical spirit or essential features. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not limiting. The scope of the present invention should be construed as including all changes or modifications derived from the meaning and scope of the claims to be described later and equivalent concepts rather than the detailed description above are included in the scope of the present invention.

Claims (13)

A curcuminoid-based compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof; And steviol glycoside or a pharmaceutically acceptable salt thereof, or licorice extract or a fraction thereof; a pharmaceutical composition for preventing or treating COVID-19 comprising a complex comprising as an active ingredient:
[Formula 1]

Wherein R ¹ and R ² are each independently hydrogen, a hydroxyl group, or a C ₁ to C ₁₀ alkoxy group,
Wherein n and m are 1≤n≤5 and 1≤m≤5.
A curcuminoid-based compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof; And a steviol glycoside or a pharmaceutically acceptable salt thereof, or a licorice extract or a fraction thereof; comprising as an active ingredient a complex comprising a composition for enhancing immunity:
[Formula 1]

Wherein R ¹ and R ² are each independently hydrogen, a hydroxyl group, or a C ₁ to C ₁₀ alkoxy group,
Wherein n and m are 1≤n≤5 and 1≤m≤5.
The composition according to claim 2, wherein the immune enhancement is any one or more activity or cell number enhancement selected from the group consisting of Th1 cells, CD8 ⁺ T cells, and NK cells.
The composition according to claim 1 or 2, wherein the curcuminoid-based compound represented by Formula 1 is a compound represented by any one of Formulas 2 to 4 below, or a mixture thereof:
[Formula 2]

[Formula 3]

[Formula 4]

.
The composition according to claim 1 or 2, wherein the steviol glycoside is derived from Stevia rebaudiana Bertoni .
The composition according to claim 1 or 2, wherein the licorice is at least one selected from the group consisting of Glycyrrhiza inflata BATALIN, Glycyrrhiza uralensis FISCHER and Glycyrrhiza glabra LINNE.
The composition according to claim 1 or 2, wherein the composition is for oral administration.
A method for preventing or treating COVID-19, comprising administering the composition of claim 1 to a non-human subject.
The method of claim 8, wherein the administration is oral administration.
A curcuminoid-based compound represented by Formula 1 below or a food-acceptable salt thereof; And a steviol glycoside or a food chemically acceptable salt thereof, or a licorice extract or a fraction thereof; a food composition for preventing or improving COVID-19, including a complex comprising:
[Formula 1]

Wherein R ¹ and R ² are each independently hydrogen, a hydroxyl group, or a C ₁ to C ₁₀ alkoxy group,
Wherein n and m are 1≤n≤5 and 1≤m≤5.
A curcuminoid-based compound represented by Formula 1 below or a food-acceptable salt thereof; And a steviol glycoside or a food chemically acceptable salt thereof, or a licorice extract or a fraction thereof; comprising a complex comprising a food composition for enhancing immunity:
[Formula 1]

Wherein R ¹ and R ² are each independently hydrogen, a hydroxyl group, or a C ₁ to C ₁₀ alkoxy group,
Wherein n and m are 1≤n≤5 and 1≤m≤5.
The food composition according to claim 10 or 11, wherein the immune enhancement is any one or more activity or cell number enhancement selected from the group consisting of Th1 cells, CD8 ⁺ T cells, and NK cells.
The food composition according to claim 10 or 11, wherein the curcuminoid-based compound represented by Formula 1 is a compound represented by any one selected from the following Formulas 2 to 4, or a mixture thereof:
[Formula 2]

[Formula 3]

[Formula 4]

.

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