JP7555211B2 - Composition for lowering blood pressure - Google Patents

Description

The present invention relates to a composition for lowering blood pressure that contains a plant extract.

Hypertension is one of the most common lifestyle-related diseases, and the number of patients is increasing year by year. Hypertension is known to cause a variety of disorders, including cerebral hemorrhage, cerebral infarction, heart failure, angina pectoris, myocardial infarction, and renal failure.

Substances that can lower blood pressure have been explored, and calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, diuretics, sympathetic nerve suppressants, and other drugs have been put to practical use. However, due to changes in consumer preferences in recent years, there is a growing demand for medicines and health functional foods that contain active ingredients of natural origin.

Licorice, derived from a plant belonging to the genus Glycyrrhiza in the family Fabaceae, has been used as a herbal medicine since ancient times and is known to have various effects such as antispasmodic, analgesic, antitussive, and expectorant.

The above-ground parts of licorice (leaves and stems) were previously treated as waste because they could not be used as pharmaceutical raw materials. However, it has become known that extracts from the above-ground parts of licorice have various effects, such as promoting collagen production (Patent Document 1), improving bone metabolism (Patent Document 2), scavenging active oxygen and radicals (Patent Document 3), hair cosmetics (Patent Document 4), promoting ceramide synthesis (Patent Document 5), suppressing increased expression of stem cell growth factor (Patent Document 6), suppressing increased expression of endothelin-1 mRNA (Patent Document 7), anti-glycation (Patent Document 8), promoting DKKI expression and whitening based on the promoting effect of DKKI expression (Patent Document 9), activating peroxisome proliferator-activated receptors (Patent Document 10), improving the composition ratio of intestinal flora, anti-chronic mild inflammation, and maintaining healthy obesity (Patent Document 11).

Furthermore, a preparation for lowering blood pressure, etc., which contains a licorice extract that does not contain glycyrrhizinic acid (Patent Document 12), and a composition for preventing or improving hypertension, etc., which contains a licorice hydrophobic extract (Patent Documents 13 and 14) are also known.

However, it has not been known until now that extracts from the aerial parts of licorice have ACE inhibitory effects or blood pressure lowering effects.

JP 2000-191498 A JP 2002-179585 A JP 2003-081744 A JP 2004-285018 A JP 2008-255051 A JP 2008-273875 A JP 2010-215571 A JP 2012-121874 A JP 2017-048155 A JP 2009-242333 A International Publication No. 2017/094892 JP 2002-114695 A International Publication No. 2002/047699 International Publication No. 2008/143182

The present invention aims to provide a composition that has a blood pressure improving effect, such as lowering blood pressure. In addition, the present invention aims to provide a food or medicine that contains the composition as an active ingredient for preventing or alleviating diseases related to ACE or blood pressure.

As a result of extensive research, the inventors have discovered that an extract from the above-ground parts of a plant belonging to the genus Glycyrrhiza in the family Leguminosae has angiotensin-converting enzyme (ACE) activity inhibitory effects and blood pressure lowering effects, leading to the completion of the present invention.
That is, the present invention includes the following aspects.
[1] A composition for lowering blood pressure, comprising an extract from the aerial parts of a plant belonging to the genus Glycyrrhiza of the family Leguminosae.
[2] A composition having angiotensin-converting enzyme (ACE) inhibitory activity, characterized in that it contains an extract from the aerial parts of a plant belonging to the genus Glycyrrhiza of the family Leguminosae.
[3] The composition described in [1] or [2], wherein the above-ground part is a leaf and/or a stem.
[4] The composition according to any one of [1] to [3], wherein the extract of a plant belonging to the genus Glycyrrhiza of the family Fabaceae is an extract extracted with water, an organic solvent, or a mixture thereof.
[5] The composition according to [4], wherein the organic solvent is at least one selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, acetone, 1-butanol, 2-butanol, 2-methyl-2-propanol, propylene glycol, glycerin, methyl acetate, ethyl acetate, hexane, diethyl ether, 2-butanone, cyclohexane, dichloromethane, edible fats and oils, propane, butane, 1,1,1,2-tetrafluoroethane, and 1,1,2-trichloroethene.
[6] The composition according to any one of [1] to [5], wherein the concentration of the extract from the aerial parts of a plant belonging to the genus Glycyrrhiza of the family Fabaceae is 0.20 mg/mL or more.
[7] The composition according to any one of [1] to [6], wherein the plant belonging to the genus Glycyrrhiza of the family Fabaceae is the species Glycyrrhiza uralensis.
[8] The composition according to any one of [1] to [7], which is for consumption or drinking.
[9] A food or medicine for preventing or alleviating a blood pressure-related disease, comprising the composition according to any one of [1] to [8] as an active ingredient.
[10] A food or medicine for preventing or alleviating a disease associated with angiotensin-converting enzyme (ACE), comprising the composition according to any one of [1] to [8] as an active ingredient.

The composition of the present invention has ACE inhibitory activity and antihypertensive effect, and therefore can prevent or alleviate diseases related to ACE or blood pressure.In addition, the composition of the present invention has high safety because it uses extracts derived from natural sources as active ingredients.In addition, the content of glycyrrhizic acid, which may cause an increase in blood pressure, is extremely low.
Therefore, the composition of the present invention is useful as a food or medicine for preventing or alleviating diseases related to ACE or blood pressure.
Furthermore, it is possible to effectively utilize parts of plants belonging to the genus Glycyrrhiza in the family Leguminosae (leaves and stems) that could not previously be used as pharmaceutical raw materials.

The composition of the present invention contains an extract from the above-ground parts of a plant belonging to the genus Glycyrrhiza of the family Fabaceae. Examples of plants belonging to the genus Glycyrrhiza of the family Fabaceae include Glycyrrhiza acanthocarpa, G. aspera, G. astragalina, G. bucharica, G. echinata (Russian licorice species), G. eglandulosa, G. foetida, G. foetidissima, G. glabra (Spanish licorice species), G. gontscharovii, G. iconica, G. inflate (Xinjiang licorice species), G. korshinskyi, G. lepidota (American licorice species), G. pallidiflora, G. squamulosa, G. triphylla, G. uralensis (Ural licorice species), G. yunnanensis, etc., and variants of these plants belonging to the genus Glycyrrhiza of the family Fabaceae can also be used. Preferred are Glycyrrhiza glabra and Glycyrrhiza uralensis, and more preferred is Glycyrrhiza uralensis. In the present invention, for example, Miyako kanzo (also called "Miyako No. 1"), which belongs to the Glycyrrhiza uralensis species of the genus Glycyrrhiza of the family Fabaceae, is used.

The characteristics of Miyako kanzo are "very tall, very many roots, very thick roots, brown root skin, strong yellow coloring in root cross section, medium number of stems, no anthocyanin coloring in stems, none or coarse stem hairs, long leaf, very wide leaf, medium leaf waviness, medium number of leaflets, very long leaf blade, very wide leaf blade, somewhat many inflorescences, medium inflorescence, quite many florets, N81A flower color, very heavy dry root weight, somewhat high glycyrrhizic acid content" (RHS color chart used). Miyako kanzo is distinguishable from the "Kita Noritake strain" by its considerably taller plant height and considerably longer leaf blade. It is also distinguishable from the "Hokkaido University strain" by its considerably taller plant height and considerably longer leaf blade. Furthermore, compared to "Medical Series," it is distinguishable by its significantly taller plant height, significantly longer leaf blade length, and later wilting.

The extract contained in the composition of the present invention is, for example, an extract from the above-ground parts of a plant belonging to the genus Glycyrrhiza of the family Fabaceae. The above-ground parts of a plant belonging to the genus Glycyrrhiza of the family Fabaceae include, for example, parts such as leaves, stems, flowers, and seeds, and are preferably leaves and/or stems. That is, the extract may be from either leaves or stems, or from leaves and stems. Preferably, it is an extract from leaves and/or stems of a plant belonging to the genus Glycyrrhiza of the family Fabaceae, and more preferably, it is an extract from leaves and/or stems of Licorice japonica.

The extract of the present invention is obtained by extracting the plant using a solvent normally used for plant extraction according to a standard method. For example, the extract can be obtained by immersing the plant in the extraction solvent and leaving it to stand or stirring it.

The plants used for extraction can be in their raw form, dried form, or chopped or crushed form.

Solvents used for extraction include those conventionally used for plant extraction, such as water, an organic solvent, or a mixture thereof.
Examples of organic solvents include methanol, ethanol, 1-propanol, 2-propanol, acetone, 1-butanol, 2-butanol, 2-methyl-2-propanol, propylene glycol, glycerin, methyl acetate, ethyl acetate, hexane, diethyl ether, 2-butanone, cyclohexane, dichloromethane, edible fats and oils, propane, butane, 1,1,1,2-tetrafluoroethane, and 1,1,2-trichloroethene.
Preferred examples include water, ethanol, or a mixture thereof. When a mixture of water and ethanol is used, the ethanol concentration in the mixture is, for example, 0.1 to 99.5 v/v%, preferably 5 to 80 v/v%, and more preferably 10 to 70 v/v%.

The extraction method may be any method that is commonly used, and for example, extraction can be performed using any device at room temperature or under heating. Specifically, the plant is placed in a treatment tank filled with a solvent, stirred from time to time to dissolve, and then centrifuged and filtered as necessary to remove the extraction residue, thereby obtaining an extract. Alternatively, a method using a supercritical fluid consisting of water, nitrous oxide, carbon dioxide, etc. may be used as an extraction method.

The amount of the solvent used for extraction is not particularly limited, but is, for example, 1 to 100 mL, preferably 5 to 50 mL, per gram of plant (calculated as dry weight).
The extraction conditions are not particularly limited as long as they are sufficient for extraction, but generally, the lower the extraction temperature, the longer the extraction time, and the higher the extraction solvent, the shorter the extraction time. The extraction temperature is appropriately set in the range of 0 to 100°C, and is preferably in the range of room temperature (about 25°C) to the boiling point of the extraction solvent. The extraction time is set in the range of 10 minutes to 24 hours, and is preferably in the range of 30 minutes to 5 hours. When water is used as the extraction solvent, the extraction conditions are, for example, about 20 to 95°C and about 30 minutes to 3 hours. When ethanol or a mixed solvent of water and ethanol is used as the extraction solvent, the extraction conditions are, for example, about 20 to 80°C and about 30 minutes to 3 hours.
The extraction may be performed once or multiple times to increase the yield.

The obtained extract can be used as it is as the composition of the present invention. If necessary, the extract may be subjected to purification for the purpose of decolorization or deodorization. Examples of purification methods include activated carbon treatment, adsorption treatment, and ion exchange resin treatment.

The extract may be further concentrated or concentrated to dryness, diluted with a suitable solvent, or dried to powder after adding an excipient as necessary. Methods for concentration or concentration to dryness include, for example, vacuum concentration (e.g., a method using an evaporator) and membrane concentration. Methods for powdering include, for example, spray drying, freeze drying, and fluidized bed drying. Excipients used to powderize the extract include those that have been conventionally used, such as modified starch and starch hydrolysates (e.g., dextrin, maltodextrin).

The "extract" in this invention includes various solvent extracts obtained by the above-mentioned extraction methods, their purified fractions, their dilutions, their concentrates, and their dried products (powders, etc.).

The amount of the extract from the above-ground part of the plant belonging to the genus Glycyrrhiza of the family Leguminosae contained in the composition of the present invention is not particularly limited as long as it is an amount that can exert a desired effect.For example, when the composition of the present invention is a liquid composition, the lower limit of the concentration in the liquid composition (dry weight of the extract/volume of the liquid composition) is, for example, 0.01 mg/mL or more, preferably 0.10 mg/mL or more, and the upper limit is, for example, 100 mg/mL or less, preferably 10 mg/mL or less.
When the composition of the present invention is a solid composition, the lower limit of the blending ratio in the solid composition (dry weight of extract/dry weight of composition) is, for example, 0.01 wt % or more, preferably 0.1 wt % or more, and the upper limit is, for example, 99 wt % or less, preferably 50 wt % or less.

The extract of the present invention has an inhibitory effect on angiotensin converting enzyme (ACE) activity. ACE produces angiotensin II, which has a vasoconstricting effect in the renin-angiotensin system, which is a hypertensive system, and is also an enzyme that breaks down bradykinin, which has a hypotensive effect. Therefore, inhibiting ACE activity produces a hypotensive effect through two mechanisms: suppressing the production of angiotensin II and suppressing the inactivation of bradykinin.
Therefore, the composition of the present invention containing the extract exhibits an ACE activity inhibitory effect and is useful for improving blood pressure, particularly for lowering blood pressure.

In this context, "improving blood pressure" includes improving vasodilation in mammals such as humans, maintaining normal vasodilation, lowering blood pressure, maintaining stable blood pressure, and protecting endothelial cells of blood vessels from degeneration. Vasodilatation also refers to the dilation of blood vessels, particularly the dilation of arterioles, which results in increased blood flow to a portion of a blood vessel.

In addition, the extract of the present invention is highly safe because it is derived from a natural plant belonging to the genus Glycyrrhiza of the family Leguminosae. Therefore, the composition of the present invention is useful as a food and medicine, particularly as a food and medicine for preventing or alleviating diseases related to blood pressure or ACE.

The pharmaceutical product of the present invention is prepared by using the above extract or the above composition according to a conventional method. For example, the above extract or the above composition can be prepared into a dosage form for oral administration, such as tablets, capsules, granules, powders, oral liquids, syrups, etc., by adding or mixing the above extract or the above composition with a pharma- ceutically acceptable carrier or additive commonly used in the field of formulation technology.
Examples of the carrier or additive include excipients, disintegrants, binders, flow agents, lubricants, colorants, pH adjusters, surfactants, stabilizers, acidulants, flavors, etc. These additives are used in amounts conventionally used in the technical field of formulations.

Examples of excipients include starches such as corn starch, potato starch, wheat corn starch, rice starch, partially pregelatinized starch, pregelatinized starch, and porous starch; sugars or sugar alcohols such as lactose hydrate, sucrose, fructose, glucose, mannitol, sorbitol, erythritol, xylitol, trehalose, maltitol, powdered reduced maltose syrup, and lactitol; anhydrous calcium hydrogen phosphate, crystalline cellulose, powdered cellulose, precipitated calcium carbonate, and calcium carbonate.
Examples of disintegrants that can be used include carmellose, carmellose calcium, sodium carboxymethyl starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl starch, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose (L-HPC), and hydroxypropyl starch, and preferably, croscarmellose sodium and L-HPC.
Examples of binders that can be used include hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, copolyvidone, powdered acacia, methylcellulose, low-substituted hydroxypropyl cellulose, hypromellose, sodium carmellose, dextrin, partially pregelatinized starch, pullulan, gum acacia, agar, gelatin, tragacanth, and sodium alginate, and preferred are hydroxypropyl cellulose and hydroxypropyl methylcellulose.
Examples of the fluidizing agent that can be used include light anhydrous silicic acid, hydrous silicon dioxide, calcium silicate, magnesium silicate, magnesium aluminometasilicate, and talc, with light anhydrous silicic acid and magnesium aluminometasilicate being preferred.
Examples of lubricants include stearic acid, magnesium stearate, calcium stearate, talc, and sucrose fatty acid esters.
Examples of coloring agents include yellow ferric oxide, ferric oxide, Food Blue No. 1, Food Blue No. 2, Food Yellow No. 4, Food Yellow No. 5, Food Green No. 3, Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Red No. 104, Food Red No. 105, Food Red No. 106, food lake color, riboflavin, and riboflavin sodium phosphate.
Examples of pH adjusters include citric acid, phosphoric acid, carbonic acid, tartaric acid, fumaric acid, acetic acid, amino acids, and salts thereof.
Surfactants include sodium lauryl sulfate, polysorbate 80, polyoxyethylene (160) polyoxypropylene (30) glycol, and the like.
Examples of the stabilizer include tocopherol, tetrasodium edetate, nicotinamide, and cyclodextrins.
Examples of acidulants include ascorbic acid, citric acid, tartaric acid, and malic acid.
Examples of the flavoring include L-menthol, peppermint oil, lemon oil, vanillin, and the like.
The above-mentioned carriers or additives may be used in a suitable mixture of two or more kinds.

The pharmaceutical product of the present invention is preferably in a unit dosage form containing 0.05 to 5 g, preferably 0.1 to 1.5 g, of the extract calculated as a dry weight. Here, "unit dosage form" means a physically separate unit, each unit containing a predetermined amount of active ingredient calculated to obtain a desired effect together with a carrier or additive.

The dosage of the pharmaceutical of the present invention varies depending on the age, sex, weight, and condition of the subject to be administered, as well as the administration route, administration schedule, dosage form, and formulation composition, but is, for example, 1 to 1000 mg, preferably 5 to 500 mg. The dosage may be administered once a day, or in two or more divided doses.

The food of the present invention is produced by a conventional method using the extract or composition. For example, it is produced by a known means such as adding the extract or composition to a food, its food ingredients, or its intermediate food materials. For example, it is produced by extracting the above-ground parts of a plant belonging to the genus Glycyrrhiza of the family Leguminosae with water or ethanol, concentrating the extract, adding the obtained concentrated extract to a food material, and then preparing the food by a conventional method.

Examples of the above foods include snacks (e.g., snacks such as potato chips, baked goods such as biscuits and cookies, chocolate, gum, candy, etc.), desserts (e.g., pudding, jelly, yogurt, ice cream, etc.), staple foods such as noodles (e.g., soba, udon, ramen, pasta, etc.), cereal foods (e.g., corn flakes, oatmeal, etc.), seasonings (e.g., soup, curry, stew, etc.), processed agricultural products (e.g., jam, etc.), dairy oil foods (e.g., spreads, cheese, etc.), health foods (e.g., protein, fiber, etc.), calorie-adjusted foods, non-alcoholic beverages (e.g., roasted soybean tea beverages, grain tea, coffee beverages, black tea beverages, green tea beverages, barley tea beverages, matcha beverages, vegetable juice beverages, orange juice, grapefruit juice, soft drinks, etc.), and alcoholic beverages (e.g., beer, wine, sake, happoshu, plum wine, whiskey, brandy, shochu, vodka, rum, gin, liqueurs, cocktails, etc.).

The food of the present invention can be, for example, a general food, including nutritional supplements, health supplements, and nutritionally adjusted foods, as well as a functional health food, including a food for specified health uses, a food with nutritional functions, and a food with functional claims. For example, the food of the present invention can be a functional food that displays, based on scientific evidence, that it is expected to have a specific health purpose (for example, "It has been reported to have the function of lowering blood pressure, and is suitable for people with high blood pressure"). The food of the present invention may also be a supplement in a form for oral intake, such as a tablet, capsule, powder, granule, liquid, or syrup.

The amount of the extract contained in the food of the present invention may be any amount that can exert the desired effect, and may be determined appropriately depending on the general intake amount of the food, the type of food, the composition, etc. For example, the food of the present invention may contain the extract in the range of 0.1 to 99.0% by dry weight.

The intake amount of the food of the present invention may vary depending on the age, sex, weight, and condition of the subject taking the food, as well as the type and composition of the food, and is, for example, 1 to 1000 mg, preferably 5 to 500 mg. The intake amount may be taken once a day, or in two or three or more divided doses.

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these.

[Examples 1 to 5] Preparation of aqueous extract from leaves and stems of liquorice Approximately 300 L of water was added to 18 kg of leaves and stems of liquorice, and the mixture was extracted at 90°C for approximately 2 hours, followed by mesh filtration to obtain 250 L of extract. This extract was then concentrated under reduced pressure at approximately 60°C to obtain 9.7 kg of concentrate. 280 g of starch hydrolysate (product name: Max 1000, manufacturer: Matsutani Chemical Industry Co., Ltd.) was dissolved in this concentrate as an excipient, and 2092 g of the solution was spray-dried to obtain 498 g of dry extract.
Approximately 1.0 g of the above dried extract was extracted with 20 mL of 50% ethanol solution and then appropriately diluted with 0.1 mol/L HEPES buffer (pH 8.3) to obtain aqueous extract-containing compositions from the leaves and stems of Licorice glabra having sample concentrations of 0.26 mg/mL (Example 1), 0.28 mg/mL (Example 2), 0.30 mg/mL (Example 3), 0.34 mg/mL (Example 4) and 0.40 mg/mL (Example 5).

[Examples 6 to 10] Preparation of an ethanol extract from the leaves and stems of Licorice glabra Approximately 300 L of 30% ethanol was added to 18 kg of the leaves and stems of Licorice glabra, and the mixture was extracted at 60°C for approximately 2 hours, followed by mesh filtration to obtain 250 L of extract. This extract was then concentrated under reduced pressure at approximately 60°C to obtain 10 kg of concentrate. 200 g of starch hydrolysate (product name: Max 1000, manufacturer: Matsutani Chemical Industry Co., Ltd.) was dissolved in this concentrate as an excipient, and 2928 g of the solution was spray-dried to obtain 320 g of dry extract.
Approximately 1.0 g of the above dried extract was extracted with 20 mL of 50% ethanol solution and then appropriately diluted with 0.1 mol/L HEPES buffer (pH 8.3) to obtain compositions containing ethanol extracts from the leaves and stems of Licorice glabra having sample concentrations of 0.25 mg/mL (Example 6), 0.35 mg/mL (Example 7), 0.45 mg/mL (Example 8), 0.55 mg/mL (Example 9) and 0.65 mg/mL (Example 10).

[Reference Examples 1 to 5]
Sardine peptide (product name: Sardine Peptide N100, manufacturer: Senmi Extract Co., Ltd.) was appropriately diluted with 0.1 mol/L HEPES buffer (pH 8.3) to obtain sardine peptide-containing compositions having sample concentrations of 0.1 mg/mL (Reference Example 1), 0.2 mg/mL (Reference Example 2), 0.5 mg/mL (Reference Example 3), 0.7 mg/mL (Reference Example 4) and 0.9 mg/mL (Reference Example 5).

[Test Example 1]
1. Test Overview The angiotensin-converting enzyme (ACE) activity test was carried out based on the method described in Nakno et al. Biosci Biotechnol. Biochem. , 70, 1118-1126 (2006), in which the dipeptide decomposed by ACE from the substrate (His-His-Leu) was fluorescentized with orthophthalaldehyde (hereinafter abbreviated as "OPA"). The fluorescence intensity of the reaction product was then measured. The ACE activity inhibition was evaluated based on the relative ACE activity when the activity of the untreated group to which no test solution was added was taken as 100%. The IC ₅₀ value was calculated from a graph of the sample concentration (mg/mL) and the inhibition rate (%).

2. Samples The compositions obtained in the above Examples 1 to 10 were used as test solutions for the following samples 1) and 2). In addition, the compositions obtained in the above Reference Examples 1 to 5 were used as a positive control (sample 3)).
1) Aqueous extract from the leaves and stems of Licorice Root (Examples 1 to 5)
2) Ethanol extract from leaves and stems of Glycyrrhiza glabra (Examples 6 to 10)
3) Sardine peptide (Reference Examples 1 to 5)

3. Test method 25 μL of 0.1 mol/L HEPES buffer (pH 8.3) (untreated group) or each test solution was added to a 96-well microplate, 25 μL of 13 mU/mL ACE solution was added, and the mixture was incubated at 37 ° C for 5 minutes. 25 μL of 8 mmol/L His-His-Leu solution was added, and the mixture was reacted at 37 ° C for 30 minutes. Then, 25 μL of 0.1 mol/L sodium hydroxide solution was added to stop the reaction, 25 μL of 1% OPA solution was added, and the mixture was left at room temperature for 20 minutes. Furthermore, 25 μL of 0.1 mol/L hydrochloric acid was added, and the mixture was left at room temperature for 10 minutes, and the fluorescence intensity was measured with a microplate reader. In addition, a blank was tested in the same manner using PBS instead of 13 mU/mL ACE solution.
<Microplate reader operating conditions>
Model: SH-9000 Lab
Measurement conditions: fluorescence, endpoint mode, bottom read Excitation wavelength: 355 nm
Fluorescence wavelength: 460 nm

4. Test Results The results of the inhibition rate in each test solution are shown in Tables 1 to 3. As a result, a concentration-dependent enhancement of the inhibition of ACE activity was observed. The _IC50 value calculated from the graph showing the relationship between the sample concentration and the inhibition rate is shown in Table 4.

[Examples 11 and 12] Preparation of aqueous extract from above-ground parts of Licorice glabra Approximately 300 L of water was added to 18 kg of leaves and stems of Licorice glabra, and the mixture was extracted at 90°C for approximately 2 hours, followed by mesh filtration to obtain 250 L of extract. This extract was then concentrated under reduced pressure at approximately 60°C to obtain 9.7 kg of concentrate. 280 g of starch hydrolysate (product name: Max 1000, manufacturer: Matsutani Chemical Industry Co., Ltd.) was dissolved in this concentrate as an excipient, and 2092 g of the concentrate was spray-dried to obtain 498 g of dry extract (Examples 11 and 12).

Reference Example 6: Preparation of an aqueous extract from the underground parts of Licorice glabra About 30 L of water was added to 3 kg of Licorice glabra roots and stolons, and the mixture was extracted at 90° C. for about 2 hours, and then filtered through a mesh to obtain 23.2 L of extract. This extract was further concentrated under reduced pressure at about 60° C. to obtain 2,544 g of concentrate. 2,511 g of this concentrate was spray-dried to obtain 608 g of dry extract (Reference Example 6).

[Test Example 2]
Systolic blood pressure (SBP) was evaluated by administering a single dose of Example 11 (100 mg/kg), Example 12 (1000 mg/kg), Reference Example 6 (1000 mg/kg), Reference Example 7 (positive control, Sarden Peptide (trade name: Sarden Peptide N100, manufacturer: Senmi Extract Co., Ltd.), 1000 mg/kg), and Reference Example 8 (positive control, Captopril (manufacturer: Tokyo Kasei Kogyo Co., Ltd.), 60 mg/kg) to 14-week-old male SHR/NCrlCrlj rats. The control group was administered with a vehicle (water for injection) at a dose of 10 mL/kg. SBP was measured using a non-invasive blood pressure monitor (BP MONITOR FOR MICE & RATS, Muromachi Kikai, MODEL MK-2000) before administration of each substance (before grouping) and 2, 4, 6, and 8 hours after administration.

The results are shown in Table 5. In the groups administered the aqueous extract of the above-ground parts of licorice (Examples 11 and 12), a significant decrease was observed in SBP 2 and 8 hours after administration of 100 mg/kg and 2 hours after administration of 1000 mg/kg, compared to the control group. In the group administered the aqueous extract of the below-ground parts of licorice (Reference Example 6), a significant decrease was observed in SBP 2 hours after administration, compared to the control group. In the group administered the sardine peptide, a significant decrease was observed in SBP 6 and 8 hours after administration, compared to the control group. These results suggest that the aqueous extract of the above-ground parts of licorice, the aqueous extract of the below-ground parts of licorice, and sardine peptide have an inhibitory effect on blood pressure rise in spontaneously hypertensive rats.
N: number of rats, each value is expressed as mean ± SE.
#: P<0.05, ##: P<0.01: Significant difference compared to the control group (Dunnett's multiple comparison test)
*: P<0.05, **: P<0.01: Significant difference compared to the control group (Student's t-test)

The composition of the present invention has ACE inhibitory activity, antihypertensive effect, etc., and therefore can prevent or alleviate diseases related to ACE or blood pressure.In addition, the composition of the present invention has high safety because it uses natural extracts as active ingredients.In addition, it has been confirmed that the content of glycyrrhizic acid, which causes pseudoaldosteronism that causes hypertension, is extremely low.
Therefore, the composition of the present invention can be used as a food or medicine for preventing or alleviating diseases related to ACE or blood pressure.
Furthermore, it is possible to effectively utilize parts of plants belonging to the genus Glycyrrhiza in the family Leguminosae (leaves and stems) that could not previously be used as pharmaceutical raw materials.

Claims (10)

A composition for lowering blood pressure, characterized by containing an extract from the above-ground parts of a plant belonging to the genus Glycyrrhiza of the family Leguminosae. The composition according to claim 1 , wherein the extract has angiotensin converting enzyme (ACE) inhibitory activity. The composition according to claim 1 or 2, wherein the above-ground part is a leaf and/or a stem. The composition according to any one of claims 1 to 3, wherein the extract of a plant belonging to the genus Glycyrrhiza of the family Fabaceae is an extract extracted with water, an organic solvent, or a mixture thereof. The composition according to claim 4, wherein the organic solvent is at least one selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, acetone, 1-butanol, 2-butanol, 2-methyl-2-propanol, propylene glycol, glycerin, methyl acetate, ethyl acetate, hexane, diethyl ether, 2-butanone, cyclohexane, dichloromethane, edible fats and oils, propane, butane, 1,1,1,2-tetrafluoroethane, and 1,1,2-trichloroethene. The composition according to any one of claims 1 to 5, wherein the concentration of the extract from the above-ground parts of a plant belonging to the genus Glycyrrhiza of the family Leguminosae is 0.20 mg/mL or more. The composition according to any one of claims 1 to 6, wherein the plant belonging to the genus Glycyrrhiza of the family Fabaceae is Glycyrrhiza uralensis. The composition according to any one of claims 1 to 7, which is for consumption or consumption. A food or medicine for preventing or alleviating blood pressure-related diseases, comprising the composition according to any one of claims 1 to 8 as an active ingredient. A food or medicine for preventing or alleviating a disease associated with angiotensin-converting enzyme (ACE), comprising the composition according to any one of claims 1 to 8 as an active ingredient.