KR102048309B1 - Composition for preventing, improving or treating thrombosis comprising extract of fermented Tenebrio molitor as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating, or treating thrombosis containing a fermented Tenebrio molitor extract as an active component. The fermented Tenebrio molitor extract of the present invention is excellent in antioxidant activity and thrombolytic activity, and is obtained from a natural material, thereby not causing side effects. Therefore, the fermented Tenebrio molitor extract can be usefully used for preventing and treating diseases involving thrombosis.

Description

Composition for preventing, improving or treating thrombosis comprising extract of fermented Tenebrio molitor as effective component

The present invention relates to a composition for the prevention, improvement or treatment of thrombosis containing fermented brown gourd extract as an active ingredient.

Since ancient times, humans have used insects for food. Insects contain 50-60% protein, 8.1-59% crude fat and 4.9-12.1% iron, although the nutritional content varies depending on the species. It is known to contain (Fe), a vitamin B group, and the like. In addition, compared to meat, iron (Fe), vitamins (Vitamin A), unsaturated fatty acids are relatively rich, essential amino acids and dietary fiber is also rich.

Brown goose ( Tenebrio molitor ) belongs to the Coleoptera goose family, known as nocturnal insects, has the advantage that it is easy to industrialize because a system that can be raised and supplied in large quantities is already established. In addition, it contains a large amount of glutamic acid, which promotes the production of gamma aminobutyric acid (GABA), and the nutritional value of oleic acid, which has the effect of increasing the HDL content of the blood and lowering the content of LDL. In addition, studies have shown that it has antifungal efficacy against Candida albicans , and anti-inflammatory effects such as concentration-dependent inhibition of TNF-α, IL-6 and NO expression. Medicinal value is also enough.

On the other hand, studies that proceed with fermentation using a variety of microorganisms are still insufficient. Here, fermentation means that the microorganism is oxidized and reduced through various processes such as decomposition or synthesis using organic enzymes it has. It is reported that this can facilitate the digestion and absorption of organic matter, and can make new weaknesses or effects. Lactic acid bacteria are known to play a role in inhibiting food poisoning by secreting anti-corruption and antibacterial substances by lactic acid fermentation and inhibiting the growth of decaying bacteria by lowering the pH of the intestine. Saccharomyces cerevisiae is an alcohol. It is a yeast mainly used to produce liquor such as wine because of its excellent ability to produce Bacillus subtilis has a high proteolytic ability, which increases the content of soluble extract and produces various bioactive substances such as free amino acids and oligo-peptides. It would be expected that significant synergistic effects would be expected if fermented with these strains was a very high brown mealworm.

On the other hand, Korean Patent No. 1424125 discloses a composition for treating inflammatory diseases including brown gourd larvae, and Korean Laid-open Patent No. 2018-0019839 discloses' white spotted radish larvae and red ginseng extracts as active ingredients. Immune enhancing composition 'is disclosed, but there is no description for the composition for preventing, improving or treating thrombosis containing the fermented brown gourd extract of the present invention as an active ingredient.

The present invention is derived from the above requirements, the inventors of the present invention brown powder ( Tenebrio molitor ) powder of Lactobacillus plantarum ( Lactobacillus plantarum ) JBMI F3, Lactobacillus plantarum JBMI F5, Saccharomyces three Extracts of brown gourds fermented with Saccharomyces cerevisiae KACC 93023 or Bacillus subtilis KACC 91157 showed increased thrombolytic activity, antioxidant activity, and enzyme substrate degradation activity compared to brown gourd extracts without fermentation. By confirming that, this invention was completed.

In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of thrombosis containing fermented brown gourd extract as an active ingredient.

In addition, the present invention provides a health functional food composition for the prevention or improvement of thrombosis containing fermented brown gourd extract as an active ingredient.

In addition, the present invention is selected from the group consisting of mealworm powder of Lactobacillus Planta room (Lactobacillus plantarum), three Levy jiae a saccharide My process (Saccharomyces cerevisiae) and Bacillus subtilis (Bacillus subtilis) of (Tenebrio molitor) It provides a method for producing fermented brown mealworms having enhanced antithrombotic, antioxidant and enzymatic substrate degradation activity, comprising the step of solidifying fermentation with one or more strains.

Fermented brown gourd extract of the present invention is excellent in antithrombotic, antioxidant and enzymatic substrate degrading activity, pharmaceutical or functional food composition for the prevention and improvement of adult diseases such as coronary artery disease, heart disease, stroke that can be caused by blood clots It can be very useful as a novel natural material of.

1 is a result of measuring the DPPH radical scavenging activity of the fermented brown rice wine water extract and the non-fermented brown rice wine water extract. Butylated hydroxytoluene (BHT); Positive control group, N; Water extract of unfermented brown mealworm, F3; Water extract of brown rice wine fermented with Lactobacillus plantarum JBMI F3 strain, F5; L. plantarum L. plantarum water extract of brown rice wine fermented with JBMI F5 strain, Ba9; Water extract of brown rice wine fermented with L. gasseri JBMI Ba9 strain, Ak; Water extract of brown rice wine fermented with Aspergillus kawachii KCCM 32819 strain, Sc; Water extract of brown rice wine fermented with Saccharomyces cerevisiae strain KACC 93023, Bs; Water extract of brown rice wine fermented with Bacillus subtilis KACC 91157 strain.
Figure 2 is the result of measuring the fibrinolytic activity of the fermented brown rice wine water extract and the non-fermented brown rice wine water extract. A, B; Clear zone, C, in which thrombolytic (antithrombotic) activity has been shown; A graph quantifying the clear zone. 0; Water extract of unfermented brown rice wine, 1; Water extract of brown rice wine fermented with Lactobacillus plantarum JBMI F3 strain, 2; Water extract of brown rice wine fermented with Lactobacillus plantarum JBMI F5 strain, 3; Water extract of brown rice wine fermented with Lactobacillus gastri JBMI Ba9 strain, 4; Water extract of brown rice wine fermented with Aspergillus Kawachi KCCM 32819 strain, 5; Water extract of brown rice wine fermented with Saccharomyces cerevisiae KACC 93023 strain, 6; Water extract of brown rice wine fermented with Bacillus subtilis KACC 91157 strain.
Figure 3 is the result of measuring the enzyme substrate degradation activity of fermented brown rice wine water extract and non-fermented brown rice wine water extract. 0; Water extract of unfermented brown rice wine, 1; Water extract of brown rice wine fermented with Lactobacillus plantarum JBMI F3 strain, 2; Water extract of brown rice wine fermented with Lactobacillus plantarum JBMI F5 strain, 3; Water extract of brown rice wine fermented with Lactobacillus gastri JBMI Ba9 strain, 4; Water extract of brown rice wine fermented with Aspergillus Kawachi KCCM 32819 strain, 5; Water extract of brown rice wine fermented with Saccharomyces cerevisiae KACC 93023 strain, 6; Water extract of brown rice wine fermented with Bacillus subtilis KACC 91157 strain.

In order to achieve the object of the present invention, the present invention provides a pharmaceutical composition for the prevention or treatment of thrombosis containing fermented brown gourd extract as an active ingredient.

In the pharmaceutical composition for preventing or treating thrombosis according to the present invention, the fermented brown gourd is a powder of brown gourd ( Tenebrio molitor ), Lactobacillus plantarum ( Lactobacillus plantarum ), Saccharomyces cerevisiae ( Saccharomyces cerevisiae ) and Bacillus subtilis ( Bacillus subtilis ) may be fermented with one or more strains selected from the group consisting of, preferably may be fermented with Bacillus subtilis strains, but is not limited thereto.

In the pharmaceutical composition for preventing or treating thrombosis of the present invention, the fermented brown gourd extract may be extracted from fermented brown gourd using water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water, It may be extracted using ethanol or methanol, most preferably may be extracted using water, but is not limited thereto.

Fermented brown gourd extract of the present invention is characterized in that the antithrombotic, antioxidant and enzyme substrate decomposition effect is superior to the brown gourd extract not fermented. The enzyme substrate may be starch, and the fermented brown mealworm extract of the present invention has α-amylase activity.

As used herein, the term "thrombosis" refers to a disease caused by a thrombus, also called a thromboembolism, and particularly refers to a disease in which blood vessels are blocked by a thrombus.

The term "thrombosis" refers to agglomeration of blood components consisting primarily of fibrin surrounding platelets and cellular components, intermingled with other formed blood elements of the blood and consisting mainly of aggregates of platelets and fibrin.

Diseases that have an anti-thrombotic pharmaceutical composition comprising the fermented brown gourd extract of the present invention as an active ingredient have a prophylactic or therapeutic effect, and include, for example, high blood pressure, heart disease, stroke, and myocardial infarction, but are not limited thereto. And diseases caused by aggregation of platelets may all be included therein.

The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients or diluents commonly used in the manufacture of pharmaceutical compositions.

In addition, the pharmaceutical compositions of the present invention may be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, external preparations, suppositories, and injections according to conventional methods.

Carriers, excipients, and diluents that may be included in the pharmaceutical composition comprising the fermented brown gourd extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, Various compounds including gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil And mixtures. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, which solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin in the fermented brown meal extract. The mixture is prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups. In addition to the commonly used simple diluents, water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, utopsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The preferred dosage of the pharmaceutical composition of the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. The pharmaceutical composition of the present invention can be administered to various mammals such as rats, mice, livestock, humans, and the like. All modes of administration can be expected, for example, but not limited to oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

The present invention also provides a health functional food composition for the prevention or improvement of thrombosis containing fermented brown gourd extract as an active ingredient.

Fermented brown gourd extract according to the present invention is characterized in that the antithrombotic, antioxidant and enzyme substrate decomposition effects are superior to the brown gourd extract that is not fermented.

The dietary supplement composition of the present invention may be prepared in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup, effervescent tablet and beverage, but is not limited thereto. The dietary supplement composition is not particularly limited as long as it can be ingested to prevent or improve thrombosis.

When the health functional food composition of the present invention is used as a food additive, the health functional food composition may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The active ingredient may be appropriately used depending on the purpose of use (prevention or improvement). However, in the case of long-term intake for health control purposes, it can be used in an amount in a range without any problem in terms of safety. There is no particular limitation on the kind of food. Examples of foods to which the health functional food composition may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products, including ice cream, various soups, drinks, tea Drinks, alcoholic beverages, vitamin complexes, and the like, and include all health foods in the conventional sense.

In addition, the nutraceutical composition of the present invention may be prepared as a food, in particular a functional food. Functional foods of the present invention include ingredients that are commonly added in food production, and include, for example, proteins, carbohydrates, fats, nutrients and seasonings. For example, when prepared with a drink, natural carbohydrates or flavors may be included as additional ingredients in addition to the active ingredient. The natural carbohydrates can be monosaccharides (e.g. glucose, fructose, etc.), disaccharides (e.g. maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g. dextrins, cyclodextrins, etc.) or sugar alcohols (e.g. , Xylitol, sorbitol, erythritol and the like). The flavourant may be a natural flavourant (eg, taumartin, stevia extract, etc.) and a synthetic flavourant (eg, saccharin, aspartame, etc.). Various nutritional supplements, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonic acid The carbonation agent etc. which are used for a drink can be contained further.

The present invention also relates to a powder of brown meal ( Tenebrio molitor ) selected from the group consisting of Lactobacillus plantarum , Saccharomyces cerevisiae and Bacillus subtilis . It provides a method for producing fermented brown mealworms having enhanced antithrombotic, antioxidant and enzymatic substrate degradation activity, comprising the step of solidifying fermentation with one or more strains.

Specifically, the method for preparing fermented brown gourd according to an embodiment of the present invention, Lactobacillus plantarum JBMI F3, Lactobacillus plantarum JBMI F5, Saccharomyces three to 10 g of brown gourd powder Saccharomyces cerevisiae KACC 93023 or Bacillus subtilis KACC 91157 strains were inoculated, Saccharomyces cerevisiae and Bacillus subtilis strains were 30 ° C, and Lactobacillus plantarum strains were 37 ° C. At 3 days each may be prepared by solid phase fermentation, but is not limited thereto.

Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

Example  1. Experimental materials and fermentation conditions

The dried brown rice cooker used in the present invention was purchased in a native village (Gyeongju, South Korea) in June 2017, powdered, and then refrigerated. The fermentation of brown gourds includes Lactobacillus plantarum JBMI F3 (F3), L. plantarum ( Lactobacillus plantarum ), three kinds of lactic acid bacteria, which were distributed from Jeonju AgroBio-Materials Institute. ) JBMI F5 (hereinafter F5) and L. gasseri JBMI Ba9 (hereinafter Ba9); One fungus, Aspergillus kawachii KCCM 32819 (hereinafter Ak); Saccharomyces, a type of yeast Saccharomyces cerevisiae ) KACC 93023 (hereinafter Sc); And one strain of Bacillus subtilis KACC 91157 (hereinafter referred to as Bs); a total of six strains were used.

The six strains were pre-incubated and centrifuged to obtain only 10% (v / w) of the cells, and then inoculated into 10 g of brown rice wine powder, and the strains Ak, Sc and Bs at 30 ° C., F3, F5 and Ba9 strain was solid-phase fermented at 37 ℃. In order to prevent the fermentation from drying during the fermentation, it was moistened with sterilized distilled water. After 3 days of fermentation, the fermentation product was naturally dried for 2 days, and then powdered and stored.

Example 2 Preparation of Fermented Brown Rice Wine Extract and Non Fermented Brown Rice Wine Extract

10 times purified water was mixed with 100 g of fermented brown gourd powder and brown gourd powder, and then extracted three times with stirring for 3 hours in a constant temperature water bath at 37 ° C., 95% ethanol and 95% methanol The extract was prepared and filtered through an Adventec 110 mm No. 2 filter paper (Toyo 2A; Toyo Roshi, Tokyo, Japan) and used for the experiment.

Example 3. Determination of Sugar, pH and Acidity

In order to confirm the sugar content of the fermented brown gourd extract and the non-fermented brown gourd extract fermented with each of the six strains, 500 μl of each extract of the 10% (w / v) concentration prepared in Example 2 was taken, Total soluble solids (° Brix) were measured with a hand refractormeter (Kruss, Germany). pH was measured with a pH meter (SevenCompactTM pH / Ion S220, Mettler-Toledo Ag, Switzerland). The titratable acidity was added to the Erlenmeyer flask by adding 25 ml of tertiary purified water and 100 µl of extract, respectively, 3 drops of 1% phenolphthalein solution was titrated with 0.1 N sodium hydroxide (NaOH), and the consumption was converted into total acidity. . As the total acidity of each extract, acetic acid (0.0006) was applied to the formula.

Total acidity (%, W / V) = [(titrated 0.1 N NaOHmlⅹ0.0006) / mlml of sample] ⅹ100

As a result of measuring the sugar content, the water extract of the fermented brown gourd was found to be 2.0 ° Brix, whereas the water extracts of fermented brown gourd fermented with Ak and Bs strains were found to be 3.0 to 6.8 ° Brix, respectively. It was found that the sugar content was significantly increased compared to the extract, and the ethanol extract of the fermented brown rice bran was slightly increased compared to the ethanol extract of the non-fermented brown rice bran, and the fermented brown meal and the non-fermented brown meal with methanol as the extraction solvent. All methanol extracts were identified as 0 ° Brix (Table 1).

In addition, as a result of the pH measurement, the water extract of the fermented brown meal, the water extract of the fermented brown meal, fermented with Sc and Bs strains slightly increased compared to the water extract of the non-fermented brown meal, but the ethanol and The methanol extract was found to have a similar pH level compared to the ethanol and methanol extracts of the non-fermented brown rice bran (Table 2).

In addition, as a result of measuring the titratable acidity, the water extract of brown gourd fermented with Ak and Bs strains was increased compared to the water extract of unfermented brown gourd, but in the case of fermented brown gourd ethanol extract, In comparison, the titratable acidity was found to decrease. In the case of the fermented brown rice wine methanol extract, the acidity was confirmed to be similar to the methanol extract of the non-fermented brown rice wine (Table 3).

Example 4. Antioxidant Activity Assay

4-1. DPPH  Free radicals Scavenging power  Measure

DPPH free radical scavenging activity is characterized by the extraction of fermented brown edible water extract and unfermented brown edible water extract of 1% (w / v) brown edible powder from spectrophotometer, Spectramax Plus 384, Molecular Devices Corp, USA) measured the absorbance values at 528 nm and expressed the difference in absorbance for the extracts of brown rice wine before and after fermentation in percentage (%). The positive control was measured in the same manner as the above by adding a synthetic antioxidant BHT (Butylated hydroxytoluene) at a concentration of 0.05%.

As a result, the radical scavenging activity was significantly increased in the water extracts of fermented brown mealworms (about 46.19 and 51.54%) compared to the water extracts of non-fermented brown mealworms (about 36.06%) and fermented with Ak and Bs strains, respectively. In ethanol and methanol extracts, brown gourd extracts fermented with Ak strain showed radical scavenging activity, but not significant values (FIG. 1).

4-2. Determination of Total Phenolic and Total Flavonoid Content

Total phenol content was determined using the Folin-Denis method. When phenolic solution (Folin-ciocalteu's phenol reagent) was treated to 10% (w / v) brown edible powder and fermented brown edible extract, the phenolic substance reacted with phosphomolybdic acid and turned blue. It was changed and measured by measuring the absorbance at 760 nm. At this time, the standard calibration curve was measured in the same manner as above with tannic acid at a constant concentration (0-500 μg / mL), and the content was expressed in mg / 100 g.

In addition, the total flavonoid content was 1% (w / v) brown gourd powder, fermented brown gourd extract and non-fermented brown gourd extract in purified water, 5% sodium nitrite (NaNO ₂ ) solution, and 10% aluminum chloride hexahydrate (AlCl ₃ 6H ₂ O) were mixed and reacted to calculate the absorbance values at 510 nm. At this time, the total flavonoid content was calculated from the standard calibration curve prepared after measuring (+)-catechin hydrate as a standard at a constant concentration (20-200 μg / ml) in the same manner as described above, and mg / 100 In g.

As a result, the total phenolic content was significantly increased in the water extracts of brown fishes fermented with Ak and Bs strains, respectively, compared to the water extracts of non-fermented brown fishes. Total phenolic content was higher than that of unfermented brown rice bran extract. When extracted with methanol, the level was similar or decreased, with or without fermentation. In addition, the total polyphenol content was markedly increased in the content of the total flavonoids in the brown gourd water extract fermented with the Bs strain compared to the water extract of the non-fermented brown gourd, and showed similar levels when extracted with other solvents ( Table 4).

4-3. Copper (Cu) reducing power measurement

Brown Fermented Powder 1% (w / v) Fermented Brown Fermented Water Extract and Non Fermented Brown Fermented Water Extract in 0.01 M Copper Chloride (CuCl ₂ ), 7.5 mM ethanolic neocuprorine solution and 1 M acetic acid Each of ammonium buffer (NH ₄ OAc buffer) was mixed and reacted at room temperature for 30 minutes, and then absorbance was measured at 420 nm. In order to compare the reducing power, the absorbance at 450 nm was measured by performing the above procedure on the synthetic antioxidant BHT at concentrations of 1.00%, 0.50%, 0.10%, 0.05% and 0.01%. As the copper reducing power increases, the color becomes dark orange / yellow.

As a result, the copper reducing power was significantly increased in the ethanol and methanol extracts of the fermented brown mealworms compared to the water, ethanol and methanol extracts of the non-fermented brown mealworms. It can be seen that the increase (Table 5).

Example 5. Thrombolytic Activity Assay

0.6% fibrinogen (Sigma, USA) was added to 0.05 M sodium borate buffer (pH 7.5), dissolved at 37 ° C. for 1 hour, and 10 ml aliquots were added to Petri dishes and thrombin (1000). unit, Sigma) was diluted to a concentration of 40 units / ㎖ and added to a petri dish to a total of 20 units and shaken well to uniformly mixed, the mixture was hardened for about 15 minutes to form a fibrin clot (fibrin clot) It was used later. A paper disc was placed on the fibrin medium, and 50 μl of water extract of fermented brown meal and water extract of unfermented brown meal were dripping by 50 μl of brown meal powder 10% (w / v), respectively. After the reaction in the incubator at 37 ℃ was measured the area of the zona pellucida (ring) generated by fibrin decomposition up to 6 hours at regular intervals. For the diameter, two diameters perpendicular to each other were measured. In the case of an ellipse, the area of the transparent band was obtained by measuring the longest diameter and the shortest diameter. The thrombolytic activity of brown rice wine extract was compared with the zona pellucida of plasmin, a plasma protease as a control, and was calculated by the following equation.

Thrombolytic activity (%) = solution area of sample / solution area of positive control × 100

As a result, thrombolysis occurred after 1 hour after extracting the extract, and the area of the circumference was measured after 6 hours, and the F3, F5, Sc, and Bs showed no thrombolysis in the extract of the nonfermented brown rice bran. The thrombolytic activity was significantly increased in each fermented brown gourd extract (44.9-83.7%) fermented with the strain, especially the extract of the brown gourd fermented with Bs strain was the most increased (Fig. 2). However, ethanol and methanol extracts of fermented brown mealworms or non-fermented brown mealworms showed no thrombolytic activity.

Example 6. Enzyme Substrate Resolution

In order to analyze the enzyme substrate degradation activity of fermented brown rice wine extract, the activity of α-amylase having starch resolution was measured. Starch at a concentration of 1% (w / v) was dissolved while stirring in a low heat, and 2% agarose was dissolved separately and then mixed with the dissolved starch to sterilize and prepared as a medium. 50 μl of the water extract of fermented brown rice wine and the fermented brown rice wine fermented with six strains, respectively, were added to the paper disk and separated after 30 minutes, and then KI + I (2% potassium iodide (KI) , 0.2% iodine (I ₂ )) solution was treated for 10 minutes, the solution was discarded and the size of the clear zone was measured.

As a result, a large amount of clear zones were generated in the case of brown gourd extract, and it was found that brown gourd had a degree of starch resolution even before fermentation. Comparing the ring of brown gourd extracts after fermentation, the remaining fermented extracts except the brown gourd extract fermented with Bs strain showed a tendency to decrease or disappear starch resolution than before fermentation (FIG. 3).

Claims (8)

Fermentation of the powder of brown edible ( Tenebrio molitor ) into one or more strains selected from the group consisting of Lactobacillus plantarum , Saccharomyces cerevisiae and Bacillus subtilis A pharmaceutical composition for the prevention or treatment of thrombosis, containing the fermented brown mealworm extract as an active ingredient. delete The pharmaceutical composition for preventing or treating thrombosis according to claim 1, wherein the extract is extracted using water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. The pharmaceutical composition for preventing or treating thrombosis according to claim 1, wherein the fermented brown gourd extract has antithrombotic, antioxidant and enzymatic substrate degradation effects. According to claim 1, wherein the composition is a powder, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and injections for the prophylaxis or treatment of thrombosis, characterized in that Pharmaceutical composition. Fermentation of the powder of brown edible ( Tenebrio molitor ) into one or more strains selected from the group consisting of Lactobacillus plantarum , Saccharomyces cerevisiae and Bacillus subtilis Health functional food composition for the prevention or improvement of thrombosis containing the fermented brown mealworm extract as an active ingredient. The health functional food composition for preventing or improving thrombosis according to claim 6, wherein the composition is prepared in any one of powder, granule, pill, tablet, capsule, candy, syrup, effervescent tablet and beverage. The powder of the brown mealworm ( Tenebrio molitor ) is solidified in one or more strains selected from the group consisting of Lactobacillus plantarum , Saccharomyces cerevisiae and Bacillus subtilis . A method for producing fermented brown mealworms having enhanced antithrombotic, antioxidant and enzymatic substrate degradation activities, including fermentation.

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