Composition containing plant extract of genus philadelphus as active ingredient, for prevention, alleviation, or treatment of tuberculosis

Abstract

The present invention relates to a composition containing a plant extract of the genus Philadelphus as an active ingredient, for the prevention, alleviation, or treatment of tuberculosis. The plant extract of the genus Philadelphus significantly reduces the number of Mycobacterium tuberculosis in (in vivo samples of) mice as well as macrophages derived from mouse bone marrow infected with Mycobacterium tuberculosis, and exhibits synergistic effects on the reduction of Mycobacterium tuberculosis when co-administered with an antituberculosis agent, and thus the plant extract of the genus Philadelphus of present invention may be usefully employed as an antituberculosis agent.

Description

Composition for the prevention, improvement or treatment of tuberculosis containing extracts of plants of the genus Ginkgo as an active ingredient

[0001] The present invention relates to a composition for preventing, improving or treating tuberculosis, comprising an extract of a plant of the genus Ginkgo as an active ingredient.

[0002] This work was supported by the Chungnam National University Hospital's Natural Product New Material Development Project for Tuberculosis Treatment (June 1, 2022 - May 31, 2023) and the 'Establishment of Safety and Effectiveness of Herbal Medicine Prescriptions in Oriental Medical Institutions' project (Project Number: 1711195899, KSN1823310), a major project of the Korea Institute of Oriental Medicine under (or affiliated with) the Ministry of Science and ICT.

[0003] Tuberculosis is an infectious disease caused by infection with Mycobacterium tuberculosis, specifically Mycobacterium tuberculosis. It is estimated that one-third of the world's population is infected with the bacteria, with approximately 8 million new cases occurring each year. While most infected individuals remain asymptomatic, approximately one-tenth of those infected will develop the disease, and if left untreated, more than half of these cases will result in death.

[0004] In developed countries, the tuberculosis infection rate is less than 0.1%, and the disease incidence rate is less than 25%. In Korea, the prevalence of active pulmonary tuberculosis (prevalence rate based on X-ray) decreased from 5.1% in 1965 to 1.0% in 1995, the prevalence of bacterial positivity decreased from 0.94% to 0.22%, and the annual risk of tuberculosis infection decreased from 5.3% to 0.5%. The mortality rate per 100,000 people decreased from 10.4% in 1991 to 6.3 in 2001, but tuberculosis remains one of the top 10 causes of death.

[0005] The six-month short-term treatment regimen consists of a two-month combination of first-line antituberculosis drugs: rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by a four-month triple-agent regimen of rifampin, isoniazid, and ethambutol. Streptomycin may be used instead of ethambutol during the initial two months of intensive treatment. In this case, maintenance therapy consists of rifampin and isoniazid.

[0006] However, these antibiotics have all been around for at least 50 years, and the development of new treatments is slow. Furthermore, the emergence of multidrug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis strains is gradually reducing the effectiveness of existing treatments. Therefore, research is needed to identify new tuberculosis treatments or substances that can enhance the sensitivity of existing ones.

[0007] As for prior art related to a treatment for tuberculosis, Korean Patent No. 1833048 discloses an anti-tuberculosis pharmaceutical composition containing cholinine and a method for producing the same, and Korean Patent No. 0656969 discloses a pharmaceutical composition for treating tuberculosis and a health functional food containing a crude extract of Prickly Pear as an active ingredient. However, there is no disclosure regarding a composition for preventing, improving, or treating tuberculosis containing an extract of a plant of the genus Glaucus, specifically a thin-leaf Glaucus as an active ingredient, of the present invention.

[0008] The present invention was derived from the above-mentioned needs, and provides a composition for preventing, improving or treating tuberculosis, which contains an extract of a plant of the genus Ginkgo as an active ingredient, and the extract of the plant of the genus Ginkgo not only significantly reduces the number of tuberculosis bacteria in mouse bone marrow-derived macrophages infected with tuberculosis bacteria but also in mice (in vivo samples), and when administered in combination with an anti-tuberculosis drug, a synergistic effect on the reduction of tuberculosis bacteria was confirmed, thereby completing the present invention.

[0009] In order to solve the above problem, the present invention provides a pharmaceutical composition for preventing or treating tuberculosis containing an extract of a plant of the genus Ginkgo as an active ingredient.

[0010] In addition, the present invention provides a health functional food composition for preventing or improving tuberculosis, which contains an extract of a plant of the genus Ginkgo as an active ingredient.

[0011] In addition, the present invention provides a feed additive for preventing or improving tuberculosis containing an extract of a plant of the genus Ginkgo as an effective ingredient.

[0012] In addition, the present invention provides a veterinary composition for preventing or treating tuberculosis containing an extract of a plant of the genus Ginkgo as an active ingredient.

[0013] In addition, the present invention provides an anti-tuberculosis herbal medicine composition containing an extract of a plant of the genus Ginkgo as an effective ingredient.

[0014] In addition, the present invention provides a method for inhibiting the growth of tuberculosis bacteria by administering a plant extract of the genus Ginkgo alone or in combination with an anti-tuberculosis agent to an animal other than a human.

[0015] The present invention relates to a composition for preventing, improving or treating tuberculosis, comprising an extract of a plant of the genus Ginkgo as an active ingredient, wherein the extract of the plant of the genus Ginkgo not only significantly reduces the number of tuberculosis bacteria in mouse bone marrow-derived macrophages infected with tuberculosis bacteria, but also in mice (in vivo samples), and when administered in combination with an anti-tuberculosis drug, has a synergistic effect on reducing tuberculosis bacteria.

[0016] Figure 1 shows the results of confirming the change in the number of Mycobacterium tuberculosis H37Rv (Rv) in macrophages after treating mouse bone marrow derived macrophages (BMDM) with various types of Philadelphus plant extracts [① Philadelphus tenuifolius leaf extract, ② Philadelphus pekinensis Rupr. leaf extract, ③ Philadelphus schrenkii leaf extract, ④ Philadelphus seoulensis leaf extract, or ⑤ Philadelphus schrenckiivar. jackii Koehne leaf extract]. In the figure, 'thin leaf' refers to the group treated with the leaf extract of the thin-leafed Japanese maple (Philadelphus tenuifolius), 'baby' refers to the group treated with the leaf extract of the Japanese maple (Philadelphus pekinensis Rupr.), 'gogwang' refers to the group treated with the leaf extract of the Japanese maple (Philadelphus schrenkii), 'seoul' refers to the group treated with the leaf extract of the Seoul maple (Philadelphus seoulensis), and 'hair' refers to the group treated with the leaf extract of the Japanese maple (Philadelphus schrenckiivar. jackii Koehne). **, *** indicate that the number of tuberculosis bacteria in the group treated with the leaf extract of the Japanese maple plant was statistically significantly reduced compared to the group infected with Mycobacterium tuberculosis (Rv) (control group). ** is p<0.01, and *** is p<0.001.

[0017] Figure 2 shows the results of reducing the number of intracellular tuberculosis bacteria by infecting mouse bone marrow-derived macrophages (BMDM) with Mycobacterium tuberculosis (M. tuberculosisH37Rv; Rv) and treating with antituberculosis drugs [ⓐ Isoniazid (INH), ⓑ Rifampicin (RIF), or ⓒ Ethambutol (EMB)]. **, *** indicate that the number of tuberculosis bacteria in the antituberculosis drug-treated group was statistically significantly reduced compared to the tuberculosis-infected control group (Rv). ** is p<0.01, and *** is p<0.001.

[0018] Figure 3 shows the results confirming that the number of tuberculosis bacteria in the lungs of mice infected with tuberculosis bacteria was reduced after administering a thin-leafed magnolia leaf extract to mice. * indicates that the number of tuberculosis bacteria in the lungs was statistically significantly reduced in the thin-leafed magnolia leaf extract administration group according to the present invention compared to the tuberculosis infection group (p<0.05).

[0019] The present invention relates to a pharmaceutical composition for preventing or treating tuberculosis, comprising an extract of a plant of the genus Ginkgo as an active ingredient.

[0020] In one embodiment of the present invention, the Philadelphus genus plant may be any Philadelphus sp. plant, and preferably at least one selected from among thin-leafed Philadelphus (Philadelphus tenuifolius), baby Philadelphus (Philadelphus pekinensis Rupr.), Philadelphus schrenkii, Seoul Philadelphus seoulensis, and hairy Philadelphus (Philadelphus schrenckiivar. jackii Koehne), more preferably thin-leafed Philadelphus (or pale-leafed Philadelphus), but is not limited thereto.

[0021] The extract of the plant of the genus Ginkgo may be made from the whole plant, aerial part, underground part, leaf, stem or flower of the plant of the genus Ginkgo, preferably from the leaf, but is not limited thereto.

[0022] In one embodiment of the present invention, the composition of the present invention may further comprise an anti-tuberculosis agent in addition to the above-mentioned effective ingredient, and may further comprise one or more anti-tuberculosis agents selected from among rifampicin, isoniazid, ethambutol, and bedaquiline, and more preferably, rifampicin, isoniazid (isocontinylhydrazine), or ethambutol, but is not limited thereto.

[0023] The active ingredient of the present invention has an antibacterial activity against Mycobacterium tuberculosis H37Rv when used alone, and has a synergistic effect on antibacterial activity when administered in combination with an antituberculosis agent.

[0024] In the present invention, the synergy effect is an effect achieved through the interaction of multiple functions. When the action of one substance is enhanced by the intervention of another, the two substances are said to exhibit a synergistic effect (a synergistic effect). This refers to the interaction of the mixture to produce a total effect that is superior or more prolonged than the sum of the effects of the individual components taken independently.

[0025] The extraction solvent of the plant extract of the genus Ginkgo of the present invention may be water, a lower alcohol of C1 to C4, or a mixture thereof, and is preferably ethanol, but is not limited thereto.

[0026] The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent in addition to the above-mentioned effective ingredient.

[0027] In addition, it can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods, but is not limited thereto.

[0028] Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

[0029] When formulating, it is usually prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants.

[0030] Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing the active ingredient with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.

[0031] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include Witepsol, macrogol, Tween 61, cacao butter, laurin, and glycerogelatin.

[0032] The appropriate dosage of the pharmaceutical composition according to the present invention can be prescribed in various ways depending on factors such as the formulation method, administration method, patient age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity. The concentration of the active ingredient included in the composition of the present invention can be determined in consideration of the therapeutic purpose, patient condition, required period, etc., and is not limited to a specific concentration range.

[0033] In addition, the present invention relates to a health functional food composition for preventing or improving tuberculosis, which contains an extract of a plant of the genus Ginkgo as an active ingredient.

[0034] The composition of the present invention may further include an anti-tuberculosis agent in addition to the above-mentioned effective ingredient, and may preferably further include one or more anti-tuberculosis agents selected from rifampicin, isoniazid, and ethambutol, but is not limited thereto.

[0035] The above composition is preferably prepared in any one of the following dosage forms: powder, granules, pills, tablets, capsules, candies, syrups, and beverages, but is not limited thereto.

[0036] When the health functional food composition of the present invention is used as a food additive, the effective ingredient may be added as is or used together with other foods or food ingredients, and may be used appropriately according to a conventional method. The amount of the effective ingredient mixed may be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when manufacturing a food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the effective ingredient may also be used in an amount exceeding the above range.

[0037] There are no specific restrictions on the types of the above foods. Examples of foods to which the above active ingredients can be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and all health functional foods in the conventional sense are included.

[0038] When the composition of the present invention is used as a health beverage, it may contain various flavoring agents or natural carbohydrates as additional ingredients, as in conventional beverages. The natural carbohydrates mentioned above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclotensin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 g of the composition of the present invention.

[0039] The composition of the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

[0040] Additionally, the composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients may be used independently or in combination. While the proportions of these additives are not particularly critical, the composition of the present invention typically contains between 0.01 and 0.1 parts by weight per 100 parts by weight.

[0041] In addition, the present invention relates to a feed additive for preventing or improving tuberculosis containing an extract of a plant of the genus Ginkgo as an effective ingredient.

[0042] The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act. The term 'feed' in the present invention may mean any natural or artificial diet, meal, etc., or ingredients of the meal, which are suitable for or intended for animals to eat, ingest, and digest. The type of the feed is not particularly limited, and feed commonly used in the relevant technical field may be used. Non-limiting examples of the feed include plant feeds such as grains, roots, fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal, or grain by-products; and animal feeds such as proteins, inorganic substances, oils and fats, mineral substances, oils and fats, single-cell proteins, zooplankton, or food. These may be used alone or in combination of two or more.

[0043] In addition, the present invention relates to a veterinary composition for the prevention or treatment of tuberculosis containing an extract of a plant of the genus Ginkgo as an active ingredient.

[0044] The veterinary composition of the present invention may further comprise suitable excipients and diluents according to conventional methods. Excipients and diluents that may be included in the veterinary composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, ethanol, stearyl alcohol, liquid paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben, and mineral oil.

[0045] The veterinary composition according to the present invention may further include fillers, anticoagulants, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, etc., and the veterinary composition according to the present invention may be formulated using methods well known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to an animal, and the formulation may be in the form of powders, granules, tablets, capsules, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, suppositories, sterile injectable solutions, sterile topical preparations, etc.

[0046] The effective amount of the veterinary composition according to the present invention can be appropriately selected depending on the individual animal. This may be determined based on factors including the severity of the disease or condition, the individual's age, weight, health status, or sex, sensitivity to the active ingredient of the present invention, the route of administration, the duration of administration, other compositions combined with or used concurrently with the composition, and other factors well known in the fields of physiology and veterinary medicine.

[0047] In addition, the present invention relates to an anti-tuberculosis herbal medicine composition containing an extract of a plant of the genus Ginkgo as an effective ingredient.

[0048] The herbal medicine composition of the present invention refers to, but is not limited to, preparations made according to a traditional Korean medicine prescription. A herbal medicine formulation comprising the herbal medicine composition according to one embodiment of the present invention may be additionally provided. The herbal medicine formulation may be any formulation comprising the herbal medicine composition, and the specific formulation is not specified. For example, the herbal medicine formulation may be a liquid, pill, tablet, granule, capsule, health food, or health drink.

[0049] In addition, the present invention relates to a method for inhibiting the growth of tuberculosis bacteria by administering a plant extract of the genus Ginkgo alone or in combination with an anti-tuberculosis agent to an animal other than a human.

[0050]

[0051] Hereinafter, the present invention will be described in more detail using examples. These examples are intended solely to illustrate the present invention more specifically, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.

[0052]

[0053] Manufacturing Example 1. Manufacturing of extracts from the genus Ginkgo

[0054] For 1 kg of dried thin-leafed maple (Philadelphus tenuifolius) leaves, 15 ℓ of 70% (v / v) ethanol was added, extracted at 85°C for 3 hours, filtered, and the filtered extract was concentrated under reduced pressure and dried at 45°C to obtain a thin-leafed maple leaf extract.

[0055] Meanwhile, extracts of leaves of Philadelphus schrenkii, Philadelphus pekinensis Rupr., Philadelphus seoulensis, and Philadelphus schrenckiivar. jackii Koehne, which are plants of the genus Philadelphus, were obtained using ethanol in the same manner as the thin-leaf Philadelphus.

[0056]

[0057] Example 1. Confirmation of the effect of reducing tuberculosis bacteria in macrophages infected with Mycobacterium tuberculosis by treatment with plant extracts of the genus Ginkgo and anti-tuberculosis drugs.

[0058] To measure the effects of plant extracts from the genus G. japonica and antituberculosis drugs on the number of Mycobacterium tuberculosis in macrophages, BMDMs were infected with H37Rv, and then the number of Mycobacterium tuberculosis colonies was counted after adding plant extracts from the genus G. japonica and antituberculosis drugs, respectively.

[0059] Specifically, macrophages (BMDM) extracted from the bone marrow of 6-week-old C57BL / 6 female mice were counted and infected with Mycobacterium tuberculosis H37Rv to an MOI of 1. After 3 hours, the medium was replaced with a medium containing a plant extract of the genus Ginkgo (200 μg / mL) or an antituberculosis drug (100 ng / mL), respectively, and cultured for 48 hours at 37°C in 5% CO2. After that, 500 μl of sterilized triple-distilled water was added to each well to collect intracellular tuberculosis bacilli and diluted 10-fold, up to a total dilution of 100-fold. To measure the number of viable intracellular tuberculosis bacilli, 10 μl was dispensed into a tuberculosis selective medium (7H10 medium) containing ampicillin (25 ng / mL) and cultured at 37°C for 2 weeks. Thereafter, the number of intracellular bacteria was measured by colony-forming unit (CFU) analysis.

[0060] As a result, as disclosed in FIGS. 1 and 2, it was confirmed that the effect of inhibiting the proliferation of tuberculosis bacteria was excellent in the group treated with the plant extract of the genus Gwangnamu or the group treated with the anti-tuberculosis agent.

[0061]

[0062] Example 2. Confirmation of the effect of reducing tuberculosis bacteria in macrophages infected with Mycobacterium tuberculosis by treatment with the leaf extract of the thin-leafed maple alone or in combination with an anti-tuberculosis drug.

[0063] Bone marrow-derived macrophages (BMDM) from 6-week-old C57BL / 6 female mice were counted and infected with Mycobacterium tuberculosis H37Rv at an MOI of 1. Three hours after infection, the medium was replaced with medium containing various concentrations of the leaf extract of the deciduous tree (50 μg / mL) and / or antituberculosis drugs (rifampicin (0.1 μg / mL), isoniazid (0.1 μg / mL), or ethambutol (4 μg / mL)). After culturing for 48 hours at 37°C and 5% CO2, the number of viable tuberculosis bacilli within the cells was measured to determine the minimal inhibitory concentration (MIC). The MIC was defined as the lowest concentration that inhibited bacterial growth by ≥99%.

[0064] The FIC value for quantifying the interaction between the thin-leafed maple leaf extract and the antituberculosis drug was calculated using Equation 1 below, and the criteria for the interaction according to the result value are disclosed in Table 1.

[0065] [Formula 1]

[0066] FIC value(ΣFIC index )=FIC B +FIC A (A = Thin-leafed magnolia extract, B = Antituberculosis agent)

[0067] FIC RMP =MIC B combination / MIC B alone

[0068] FIC A =MIC A combination / MIC A alone

[0069] FIC value(x)Effectx ≤0.5Synergistic0.5<x ≤0.75Partial synergy0.75<x ≤1.0Additive1.0<x ≤4.0No interaction effectx >4.0Antagonistic

[0070] As a result of quantifying the interaction between the thin-leafed magnolia leaf extract and anti-tuberculosis drugs, as shown in Table 2 below, when the thin-leafed magnolia leaf extract was used alone, the minimum inhibitory concentration was 50 ㎍ / ㎖, when rifampicin and isoniazid were used alone, the minimum inhibitory concentration was 0.1 ㎍ / ㎖, and when ethambutol was used alone, the minimum inhibitory concentration was 4 ㎍ / ㎖, but when these were used in combination, the minimum inhibitory concentration was 6.25 ㎍ / ㎖ for the thin-leafed magnolia leaf extract, 0.03 ㎍ / ㎖ for rifampicin and isoniazid, and 0.3 ㎍ / ㎖ for ethambutol, confirming a synergistic effect. Therefore, when the thin-leafed magnolia leaf extract and the anti-tuberculosis drug are administered together, the anti-tuberculosis activity of the thin-leafed magnolia leaf extract is enhanced by the synergistic effect between the two substances, and the anti-tuberculosis drug, specifically, rifampicin, isoniazid, and Ethambutol may increase the drug sensitivity of tuberculosis bacteria.

[0071] Results of the treatment of Rv-infected BMDM cells with a mixture of antituberculosis drugs (rifampicin, isoniazid, or ethambutol) and the leaf extract of the thin-leafed magnolia tree. The effect of treatment on reducing tuberculosis bacteria was confirmed. MIC alone MIC combination FIC value Tuberculosis reduction effect Antibiotic (㎍ / ㎖) Thin-leafed magnolia tree leaf extract (㎍ / ㎖) RIF (㎍ / ㎖) Thin-leafed magnolia tree leaf extract (㎍ / ㎖) Thin-leafed magnolia tree leaf extract + rifampicin (RIF) 0.150 0.036.25 0.43 increase Thin-leafed magnolia tree leaf extract + isoniazid (INH) 0.150 0.036.25 0.43 increase Thin-leafed magnolia tree leaf extract + ethambutol (EMB) 450 0.36.25 0.2 increase

[0072] Example 3. Measurement of the number of tuberculosis bacteria after administering a thin-leafed extract of the leaves of the genus Amurense to H37Rv-infected mice.

[0073] To determine the effect of the extract of the leaves of the thin-leafed maple on the number of intracellular tuberculosis bacteria in vivo, mice were infected with H37Rv, and then the extract of the leaves of the thin-leafed maple was administered for 2 weeks, and the number of tuberculosis colonies in the lungs of the mice was counted.

[0074] In more detail, eight 7-week-old C57BL / 6 female mice (19 g) were infected with pathogenic tuberculosis bacteria (10 6 / 50㎕) was infected via the intratracheal route. The infected mice were divided into two groups. The negative control group was administered 0.5% CMC (Carboxymethylcellulose) used as a solution, and the experimental group was administered a thin-leafed magnolia leaf extract (100 mg / kg). The thin-leafed magnolia leaf extract was dissolved in 0.5% CMC and used. It was administered orally five times at two-day intervals starting on the third day of infection. On the 14th day of infection, the mice were sacrificed, the lungs were separated, and pulverized using a tissue grinder. The lysate of the pulverized tissue was serially diluted by a factor of 10 with 1㎖ of sterile triple-distilled water, and 10㎕ was dispensed into the tuberculosis selective medium (7H10 medium) containing ampicillin (25 ng / ㎖). The cells were cultured at 37℃ for 2 weeks, and the number of bacteria in the tissue was confirmed through a CFU (colony-forming unit) assay.

[0075] As a result, as disclosed in Fig. 3, it was confirmed that the number of tuberculosis bacteria surviving in lung cells in the experimental group treated with the extract of the leaves of the thin-leafed maple tree was significantly reduced compared to the negative control group.

[0076]

[0077] [Statistical Analysis]

[0078] All statistical analyses in the above examples were performed using GraphPad Prism 8 (GraphPad, Inc., San Diego, CA), and the Mann-Whitney test was used to indicate significant differences between the two groups. (P values: ***p<0.001, **p<0.01, and *p<0.05)

Claims

1. A pharmaceutical composition for the prevention or treatment of tuberculosis containing an extract of a plant of the genus Ginkgo as an active ingredient.

2. A pharmaceutical composition for preventing or treating tuberculosis, characterized in that in paragraph 1, the plant extract of the genus Philadelphus is at least one selected from a thin-leafed Philadelphus tenuifolius leaf extract, a baby Philadelphus pekinensis Rupr. leaf extract, a Philadelphus schrenkii leaf extract, a Seoul Philadelphus seoulensis leaf extract, and a hairy Philadelphus schrenckiivar. jackii Koehne leaf extract.

3. A pharmaceutical composition for the prevention or treatment of tuberculosis, characterized in that it further comprises an anti-tuberculosis agent in addition to the effective ingredient in paragraph 1.

4. A pharmaceutical composition for preventing or treating tuberculosis, characterized in that the anti-tuberculosis agent in paragraph 3 is at least one selected from rifampicin, isoniazid, and ethambutol.

5. A pharmaceutical composition for preventing or treating tuberculosis, characterized in that the effective ingredient in paragraph 1 has antibacterial activity against Mycobacterium tuberculosis H37Rv.

6. A pharmaceutical composition for preventing or treating tuberculosis, characterized in that the extraction solvent of the plant extract of the genus Gwangnamu in the first paragraph is water, a lower alcohol of C1 to C4, or a mixture thereof.

7. A pharmaceutical composition for the prevention or treatment of tuberculosis, characterized in that, in addition to the effective ingredient in paragraph 1, it further comprises a pharmaceutically acceptable carrier, excipient or diluent.

8. A health functional food composition for preventing or improving tuberculosis containing an extract of a plant of the genus Ginkgo as an active ingredient.

9. A health functional food composition for preventing or improving tuberculosis, characterized in that it further comprises an anti-tuberculosis agent in addition to the effective ingredient in paragraph 8.

10. A health functional food composition for preventing or improving tuberculosis, characterized in that the composition is manufactured in any one formulation selected from powder, granules, pills, tablets, capsules, candy, syrup, and beverage in the 8th paragraph.

11. Feed additive for the prevention or improvement of tuberculosis containing extracts of plants of the genus Ginkgo as an active ingredient.

12. A veterinary composition for the prevention or treatment of tuberculosis containing an extract of a plant of the genus Ginkgo as an active ingredient.

13. An anti-tuberculosis herbal medicine composition containing an extract of a plant of the genus Gwangnamu as an active ingredient.

14. A method for inhibiting the growth of tuberculosis bacteria by administering a plant extract of the genus Ginkgo alone or in combination with an anti-tuberculosis drug to an animal other than a human.

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