Antihypertensive and method for producing the same

Abstract

To provide an antihypertensive considered to be safe and a method for producing the same.SOLUTION: An antihypertensive according to the present invention comprises leaves of sesame (Sesamum indicum) or an extract thereof as an active ingredient. A method for producing an antihypertensive according to the present invention comprises the steps of: sowing sesame (Sesamum indicum) seeds and growing them; and harvesting the grown sesame leaves.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an antihypertensive agent which is considered to be safe and a method for producing the same. [Background technology]

[0002] Although the criteria for hypertension vary depending on age and comorbidities, it generally refers to a condition in which the systolic blood pressure is 140mmHg or higher or the diastolic blood pressure is 90mmHg or higher. If hypertension persists, arteriosclerosis progresses, causing strokes and myocardial infarction, and the heart's function declines, leading to heart failure.

[0003] There are two types of hypertension: essential hypertension and secondary hypertension. Secondary hypertension is caused by diseases of the thyroid gland or adrenal glands. On the other hand, the majority of hypertension in Japanese people is essential hypertension, which has no such cause. Essential hypertension is thought to be caused by a combination of factors such as excessive salt intake, obesity, alcohol consumption, lack of exercise, stress, and genetic predisposition.

[0004] Although hypertension is not a disease in itself, as mentioned above, it can cause various diseases, so it is important to keep blood pressure within the normal range. Angiotensin II antagonists such as olmesartan are mainly used as antihypertensive drugs, but synthetic drugs are known to have various side effects. Therefore, it is necessary to pay attention to lifestyle habits such as limiting salt intake and exercising on a daily basis, but if blood pressure does not decrease, it is preferable to regularly take a safe antihypertensive drug.

[0005] Sesame has long been known as a nutritious food and is also used as a herbal medicine. Sesame oil is also extracted from the seeds due to their high oil content. Sesamin, which is contained in sesame, is said to have various physiological activities, such as antioxidant effects, cholesterol absorption inhibition, and anticancer effects.

[0006] For example, Patent Document 1 discloses a protein derived from roasted sesame having angiotensin-converting enzyme (ACE) inhibitory activity, and Patent Document 2 discloses a tripeptide derived from sesame having ACE inhibitory activity. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Patent No. 7322234 [Patent Document 2] JP 2009-84295 A Summary of the Invention [Problem to be solved by the invention]

[0008] As mentioned above, compounds with antihypertensive effects are known to include synthetic pharmaceuticals as well as sesame-derived ingredients, but the sesame-derived ingredients that have been well studied are mainly those derived from sesame seeds and sesame oil. However, lifestyle-related diseases such as hypertension remain a problem, and there remains a need for antihypertensive drugs that are safe and can be taken regularly. Therefore, an object of the present invention is to provide an antihypertensive agent which is considered to be safe and a method for producing the same. [Means for solving the problem]

[0009] The present inventors have conducted extensive research to solve the above problems, and as a result have found that sesame leaves and their extracts have excellent antihypertensive effects, leading to the completion of the present invention. The present invention will now be described.

[0010] [1] An antihypertensive agent containing sesame (Sesamum indicum) leaves or their extract as an active ingredient. [2] A method for producing an antihypertensive agent, comprising: Sowing and growing sesame (Sesamum indicum) seeds; A method comprising the step of harvesting grown sesame leaves. [3] The method according to [2] above, wherein the leaves are harvested after one or more buds are seen and before the seeds are ripe. [4] The method according to [2], further comprising the step of drying and then grinding the leaves. [5] The method described in [2] above, further comprising a step of extracting active ingredients from the leaves using a solvent to obtain an extract solution. [6] The method according to [5] above, wherein the solvent is an alcohol-based solvent or a mixed solvent of an alcohol-based solvent and water. Effect of the Invention

[0011] The active ingredient of the antihypertensive agent according to the present invention is sesame leaves or extracts thereof, which are also used for food, and therefore it is considered safe and can be taken regularly every day. Furthermore, the antihypertensive agent according to the present invention can reduce blood pressure, particularly when administered to subjects with high blood pressure. Therefore, the present invention is industrially very excellent as a health food that contributes to people's regular health. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 is a graph showing the change in blood pressure over time when hypertensive subjects were administered with molokheiya powder or the green onion powder according to the present invention. [Diagram 2] FIG. 2 is a graph showing the change in blood pressure over time when water, the angiotensin-converting enzyme inhibitor captopril, or the green onion extract according to the present invention were administered to hypertensive renal disease model rats. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] The antihypertensive agent according to the present invention contains sesame (Sesamum indicum) leaves or an extract thereof as an active ingredient. In the present disclosure, the active ingredient refers to a component having an antihypertensive effect among the components contained in the antihypertensive agent according to the present invention, in other words, the antihypertensive agent according to the present invention contains sesame leaves or an extract thereof in an amount that exerts an antihypertensive effect. Specifically, without being particularly limited, for example, the ratio of sesame leaves or an extract thereof in the antihypertensive agent according to the present invention can be 10% by mass or more and 100% by mass or less.

[0014] Sesame (Sesamum indicum) is an annual plant of the Sesamum genus in the Pedaliaceae family, and is said to have about 3,000 species, based on differences in seed shape, size, color, etc. The type of sesame used in the present invention is not particularly limited, but examples include Sa Mong Nan Net Thae and Gomazo (registered name).

[0015] Sa Mong Nan Net Thae is a small black sesame that has been cultivated in a specific area of ​​Myanmar for a long time, and is also known by the product name "Goma Kurohachi (registered trademark)". The seeds of Sa Mong Nan Net Thae are very similar in weight and appearance to the seeds of the registered lignan sesame (Registration No.: 19697, Application No.: 20790, Type of agricultural, forestry and fishery plant: Sesamum indicum L., Variety name: ITCFA2001; Registration No.: 19698, Application No.: 20791, Type of agricultural, forestry and fishery plant: Sesamum indicum L., Variety name: ITCFA2002), but the inventors have clarified through genome analysis that the two varieties are evolutionarily different, with large insertions and deletions of sequences between the two genomes. The difference in the genomes of Goma Kurohachi and lignan sesame can be verified by PCR.

[0016] Gomazou is a high-lignan variety that can be cultivated in Japan and was selected from the progeny of the high-yielding white sesame line Toyama016 and the tropical germplasm line H65 native to southern China, which has high sesamin and sesamolin contents.

[0017] Sesame leaves were listed as "green herb" in the Shennong Bencaojing, China's oldest book on herbal medicines, which is said to have been published during the Western Han Dynasty about 2,100 years ago. However, in recent years they have not been used in Chinese herbal medicine prescriptions and can be said to have been forgotten as a herbal medicine.

[0018] Sesame leaves are preferably from a plant with two or more true leaves. Sesame leaves are preferably harvested before fully ripe seeds set. Sesame leaves can also be harvested from plants with a height of 50 cm or more, plants with one or more buds but before flowering, or plants that have not yet flowered. The period from sowing to harvest can be adjusted as appropriate, and can be, for example, one month or more, preferably two months or more or 2.5 months or more, or can be 3.5 months or less, preferably three months or less.

[0019] Sesame leaves may be used as is, or may be subjected to one or more treatments selected from washing, drying, crushing, hydrolysis, and extraction. Examples of hydrolysis treatment include treatment at 25±5°C and humidity of 90% or more for 1 hour to 5 hours, or rotation in a drum followed by heating to stop hydrolysis. Hydrolysis treatment may reduce bitterness.

[0020] The form of the active ingredient of the antihypertensive agent according to the present invention is not particularly limited, and examples thereof include liquid, paste, and powder. Powder includes coarse powder, micro powder, and nano-micro powder.

[0021] The form of the antihypertensive agent according to the present invention is not particularly limited, and examples thereof include solid, gel, and liquid forms. More specifically, examples thereof include powders, fine granules, granules, tablets, coated tablets, capsules, lozenges, and liquid forms.

[0022] The antihypertensive agent according to the present invention may contain additives other than the active ingredient depending on the dosage form. Examples of additives include excipients, binders, lubricants, disintegrants, emulsifiers, stabilizers, absorption enhancers, differentiation agents, and preservatives. The amounts of the additives are not particularly limited and may be appropriately adjusted.

[0023] The antihypertensive agent according to the present invention can be produced, for example, by a method including the following steps.

[0024] 1. Sesame seeding and growing process In this process, sesame seeds are sown and grown. This process may be carried out in accordance with the usual method of growing sesame. For example, sesame seeds may be sown from mid-May to mid-June in Japan after the maximum temperature exceeds 20°C. Specifically, holes about 1 cm deep are made in the furrows, 5 to 6 seeds are placed in each hole, then the holes are covered with soil and watered thoroughly. When the plants have 1 to 2 true leaves, thin out the plants that are not growing well so that there are about 3 plants per hole, when there are 3 to 4 true leaves, thin out to 2 plants, and when there are 5 to 6 true leaves, thin out to 1 plant.

[0025] 2. Sesame leaf harvesting process In this step, the leaves of grown sesame are harvested. The harvesting time and post-processing are as described above.

[0026] 3.Extraction process In this process, the active ingredient is extracted from sesame leaves using a solvent. This process may or may not be performed, but the extraction may further enhance the antihypertensive effect of the active ingredient.

[0027] The solvent used for extraction in this step is not particularly limited and may be appropriately selected, but from the viewpoint of safety, for example, an aqueous solvent may be used. An aqueous solvent refers to water, a mixed solvent of water and a water-soluble organic solvent, or a water-soluble organic solvent. A water-soluble organic solvent refers to an organic solvent that can be mixed with water without restrictions. The ratio of the water-soluble organic solvent in the mixed solvent may be appropriately adjusted, but may be, for example, 20% by mass or more and 95% by mass or less. The ratio is preferably 30% by mass or more, 40% by mass or more, or 50% by mass or more, more preferably 60% by mass or more or 70% by mass or more, and preferably 90% by mass or less, more preferably 80% by mass or less.

[0028] Examples of the water-soluble organic solvent include alcohol solvents such as methanol, ethanol, and 2-propanol; ether solvents such as tetrahydrofuran; amide solvents such as dimethylformamide and dimethylacetamide; and sulfoxide solvents such as dimethylsulfoxide. Ethanol is a suitable water-soluble organic solvent because it is relatively less harmful to the human body. The type of water is not particularly limited, and purified water, distilled water, pure water, tap water, and the like can be used without any particular limitation.

[0029] The extraction conditions in this step are not particularly limited, and a conventional method can be used. For example, about 5 mL to 100 mL of solvent is added per 1 g of sesame leaves, and extraction is performed for about 30 minutes to 10 hours. The extraction temperature is also not particularly limited, and extraction may be performed at room temperature, below the boiling point of the solvent, or by heating under reflux. For example, when water is used as the solvent, it may be heated to 60°C or higher and 100°C or lower.

[0030] After extraction, general post-treatment may be carried out. For example, solids may be removed from the mixture after extraction by filtration or centrifugation. Furthermore, the obtained solution may be distilled, concentrated, or dried. Examples of drying methods include heat drying, vacuum drying, freeze drying, and spray drying. In addition, the active ingredient may be further purified by chromatography or the like.

[0031] The amount of the antihypertensive agent according to the present invention to be used should be appropriately adjusted depending on whether it is preventive or therapeutic use, the severity of the patient, other conditions, age, sex, etc., and is not particularly limited. For example, the antihypertensive agent according to the present invention can be used in an amount of 10 mg or more per day in terms of solid content when taken. Since the antihypertensive agent according to the present invention is very safe, the upper limit of the amount to be used is not particularly limited, but for example, the amount can be 2 g or less per day in terms of solid content when taken. In addition, the number of times per day can be about 1 time or more and 5 times or less.

[0032] The antihypertensive agent according to the present invention can be administered not only to humans but also to animals other than humans. Examples of animals to which the agent can be administered other than humans include livestock such as horses, cows, pigs, sheep, goats, camels, and llamas, sports animals such as racehorses, pet animals such as dogs and cats, laboratory animals such as mice, rats, guinea pigs, and rabbits, poultry such as chickens, ducks, turkeys, and ostriches, and seafood such as farmed fish.

[0033] The antihypertensive agent according to the present invention exhibits an extremely excellent antihypertensive effect, and is therefore effective in preventing cardiovascular diseases such as arteriosclerosis, stroke, myocardial infarction, and heart failure, in addition to lowering blood pressure. EXAMPLES

[0034] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to the following examples, and it is possible to carry out the present invention by making appropriate modifications within the scope of the above and below-mentioned aims, and all of these modifications are included in the technical scope of the present invention.

[0035] Example 1: Preparation of Aojiao Powder Goma Kurohachi (registered trademark) leaves, which were grown in Myanmar in 2020, washed and dehydrated, steamed, electrically dried, and stored, were ground using a powder mill ("HC-700" manufactured by COLDENWALL) to prepare green tea powder.

[0036] Example 2: Preparation of Green Lovage Rhizome Extract Powder 100 g of Goma Kurohachi (registered trademark) leaves, which were grown in Myanmar in 2020, washed and dehydrated, then steamed, dried electrically, and stored, were pulverized using a powder mill ("HC-700" manufactured by COLDENWALL), 1 L of 70% ethanol water was added, stirred well at room temperature, and left overnight. The solids were then filtered off, and the resulting filtrate was concentrated under reduced pressure and then dried in a desiccator to obtain 16 g of a dried product. This 16 g of dried product was powdered in a mortar and stored in a desiccator as a powdered green tea extract until use.

[0037] Example 3: Antihypertensive Test This randomized, placebo-controlled, single-blind, parallel-group comparative study was conducted in compliance with the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor and Welfare, and the Ministry of Economy, Trade and Industry Notification No. 1, "Ethical Guidelines for Life Science and Medical Research Involving Human Subjects" (issued on March 23, 2021), under the following conditions. Twelve patients with moderate hypertension (systolic blood pressure 140-159 mmHg) were randomly selected, regardless of gender or age, and randomly divided into two groups of six patients each. The group taking the powder of Example 1 was asked to take 1.5 g of the powder twice a day, in the morning and at night, for a total of 3 g per day, from the day the test started. No special instructions were given regarding diet or other lifestyle habits, and each subject was asked to measure their blood pressure non-invasively once a month and record the results. The placebo group was given the same conditions as the group taking green ginger powder, except that they took molokheiya powder instead of green ginger powder. The changes over the three months are shown in Table 1, and a graph of the average values ​​is shown in Figure 1. In Figure 1, "*" indicates that there is a significant difference of p<0.05 from the blood pressure at the start of the test.

[0038] [Table 1]

[0039] As shown in the results in Table 1 and Figure 1, the systolic blood pressure of the placebo group that took molokheiya powder remained almost unchanged even three months after starting the intake. In contrast, the systolic blood pressure of the group taking green onion powder dropped significantly from the first month compared to the baseline. As such, since blue root powder has a rapid-acting antihypertensive effect, it is presumed that blue root contains ingredients that have vasodilatory properties.

[0040] Example 4: Animal Experiments Despite satisfactory reports of antihypertensive drug therapy reducing the incidence and mortality of stroke and coronary artery disease in patients with essential hypertension, the current increase in the number of patients with hypertensive vascular disorders of end-stage renal disease, known as nephrosclerosis, is one of the major issues. As an experimental model of hypertensive renal disease, spontaneously hypertensive rats (SHRs) are known to develop severe nephrosclerosis histopathologically. While the average lifespan of wild-type rats is approximately three years, SHRs develop nephrosclerosis and die within two years. An experiment was conducted using SHRs to confirm the effect of green onion extract on blood pressure. Eighteen 7-week-old male SHRs (obtained from Japan SLC) weighing 260.1 g±0.267 were pre-bred for one week for acclimatization, and then randomly divided into a control group, a group administered with the green locust extract, and a positive control group of six animals each. For the group administered the green tea extract, the green tea extract powder of Example 2 and powdered gum arabic were suspended in water, and the green tea extract powder was forcibly orally administered to the rats in the afternoon once a day for 4 weeks using a stomach tube at a dose of 800 mg / kg body weight. Water and normal food were freely available. The control group was similarly forced to receive only water in the same amount in order to impose a similar stress. The positive control group was similarly forced to receive captopril (50 mg / kg body weight), a synthetic antihypertensive drug with angiotensin-converting enzyme inhibitory action. The blood pressure of each rat was measured once a week between 9:00 and 10:00 a.m. The results are shown in Figure 2. In Figure 2, "*" indicates that there is a significant difference of p<0.05 from the blood pressure at the start of the experiment by t-test.

[0041] As shown in Figure 2, the blood pressure of the control group, which received only water, continued to rise even after the study began. In contrast, the positive control group, which received the antihypertensive drug captopril, experienced a significant drop in blood pressure one week after the start of the study. However, captopril is a synthetic drug that carries serious side effects. In the group receiving the green tea extract, a tendency for blood pressure to decrease was observed one week after the start of administration, and blood pressure was significantly reduced two weeks later.

Claims

1. 1. An antihypertensive agent comprising sesame (Sesamum indicum) leaves or an extract thereof as an active ingredient.

2. A method for producing an antihypertensive agent, comprising the steps of: Sowing and growing sesame (Sesamum indicum) seeds; A method comprising the step of harvesting grown sesame leaves.

3. 3. The method of claim 2, wherein the leaves are harvested after one or more buds are visible and before the seeds are ripe.

4. 3. The method of claim 2, further comprising the step of grinding the leaves after drying.

5. 3. The method according to claim 2, further comprising the step of extracting the active ingredient from the leaves using a solvent to obtain an extract solution.

6. The method according to claim 5, wherein the solvent is an alcoholic solvent or a mixed solvent of an alcoholic solvent and water.

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