JP2006306747A - Agent containing tussilago farfara extract for preventing or improving life cycle-related diseases - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a useful substance having an action to prevent or improve life cycle-related diseases such as hypertension, hyperglycemia, hyperlipemia, reduction of blood fluidity, obesity, and allergic symptoms, among foods having no side effect. <P>SOLUTION: In the invention, an extract of Tussilago farfara which is a plant belonging to genus Tussilago of Asteraceae, is provided as a preventive or improving agent for life cycle-related diseases, or food and drink. This extract contains chlorogenic acid and caffeic acid on which the effect has been reported, and is higher in effect than equivalent amount of those acids, and is stable and made easily into preparation. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a preventive or ameliorating agent for lifestyle-related diseases such as hypertension, hyperglycemia, hyperlipidemia, decreased blood fluidity, obesity, allergies, etc., or food / beverage products containing a dandelion extract (particularly leaves are preferred) It is related to the application.

  The field of use includes use for oral food compositions and other general foods and drinks such as health foods.

  The second leading cause of death among Japanese is heart disease such as myocardial infarction and angina pectoris, and the third is cerebrovascular disease such as cerebral infarction and cerebral hemorrhage. These causes are thought to be due to hypertension, hyperglycemia and hyperlipidemia, decreased blood fluidity, and obesity. These symptoms are said to be lifestyle-related diseases because they are caused not only by genetic causes but also by diet and environment. In addition, hay fever and atopic dermatitis in which patients are increasing are also included in lifestyle-related diseases (Non-patent Document 1).

Ministry of Health, Labor and Welfare Minister's Secretariat Statistics Information Department "Demographic Statistics" 2002

If the intima of a blood vessel is damaged for any reason, cholesterol accumulates as an atheroma in the gap. Hyperlipidemia is likely to cause atheroma. As a result, the wall of the artery becomes thick, leading to arteriosclerosis, and the inside of the blood vessel is also narrowed, resulting in poor blood flow. At this time, if the blood pressure is high, the blood sugar level is high, or the blood fluidity is low, the state of the blood vessels deteriorates. When the intima ruptures, platelets collect to close the wound. This becomes a thrombus and clogs the blood vessel, resulting in an infarction. In order to prevent infarction, it is necessary to improve hypertension, hyperglycemia and hyperlipidemia, decreased blood fluidity, obesity and the like (Non-patent Document 2).

Bluebacks “Cholesterol Commonsense” Uso Real, 2005, Kodansha

  Allergic symptoms include illnesses such as hay fever and atopic dermatitis, and there are few but life-threatening illnesses such as anaphylactic shock (Non-patent Document 3). .

Home Medicine, Kodansha, 1991

  Antihypertensive drugs are used to improve hypertension. There are many types of antihypertensive agents, and they are properly used depending on the level of blood pressure. Antihypertensive drugs such as antihypertensive diuretics, reserpine, vasodilators, antialdosterone agents, sympathetic beta blockers, sympathetic alpha blockers, renin / angiotensin inhibitors, calcium antagonists, etc. are used. (Non-Patent Document 3).

  Dietary restriction and exercise therapy are optimal to ameliorate hyperglycemia, but if blood glucose control is still not adequate, oral hypoglycemic agents are used. Currently used oral hypoglycemic agents include sulfonyl urea agents and biguanide agents (Non-patent Document 3).

  In order to improve hyperlipidemia, there are many types of lipid metabolism-improving agents as drugs that increase the utilization of lipids in the body and treat excess accumulated lipids (Non-patent Document 3).

  Foods such as vinegar, plum dried, lemon, buckwheat, onion, natto, EPA, DHA, coenzyme Q-10 are well known to improve blood fluidity related to hyperglycemia and hyperlipidemia (Non-Patent Document 4).

Nikkei Health, 2003.4, Nikkei Inc.

In order to solve obesity, which is said to trigger all of the above symptoms, exercise, diet, etc. are recommended, while many diet foods are commercially available. Foods such as bittern, green tea, black beans, vinegar, carnitine, α lipoic acid, vitamin B group, amino acids, and brewer's yeast are well known (Non-patent Document 5).

Nikkei Health, 2003.4, Nikkei Inc.

  In order to improve allergic symptoms such as hay fever and atopic dermatitis, there are many types of corticosteroids, non-steroids and the like (Non-patent Document 3).

  In order to solve these problems, there are reports of direct application of chlorogenic acid, caffeic acid and the like. Or the intake of the plant containing many of these is known (patent documents 1-4).

JP 2002-53464 A JP 2002-308766 A JP2002-80351 JP 2004-168749 A

However, once these drugs are taken, they must last a lifetime and the use of pharmaceuticals cannot ignore the problem of side effects. Many drugs have side effects with their effectiveness. Also, new side effects that occur due to the use of many symptom-improving drugs are also a problem. Liver dysfunction has also been reported with diet foods.

In addition, chlorogenic acid and caffeic acid are unstable, and it was necessary to devise a formulation. Even in plants containing this, a higher effect was desired.

  In view of these circumstances, the present inventors are taken as food on a daily basis and improve hypertension, hyperglycemia and hyperlipidemia, decreased blood fluidity, obesity, allergic symptoms, etc. in foods without side effects. We have conducted intensive research on the development of useful substances and plants that have an effect. As a result, we found a particularly high effect on the dandelion extract (preferably an extract from leaves).

  As used herein, the term “fukitan popo” refers to a plant belonging to the genus Cantaceae that contains a large amount of chlorogenic acid and caffeic acid: leaves or branches of fuchsia poppo, leaves, flowers, flower ears, etc. Either from Europe or North America. Among these, leaves are preferable from the viewpoint of effect, and production from Europe is preferable.

  In addition, the extract of poppy dandelion of the present invention can be used in a state where various solvents, for example, water, alcohols, etc. are used alone or in any combination of two or more kinds of mixed solutions. Among these, hydrous ethanol is preferable.

  Further, the dandelion poppo extract of the present invention may be prepared by arbitrarily drying, concentrating or diluting depending on the dosage form and form of the food or drink of the lifestyle-related disease prevention or improvement agent to be applied.

  The dandelion extract of the present invention can be blended into foods and drinks as a lifestyle-related disease prevention or amelioration agent, and the blending amount is not particularly specified, but varies slightly depending on the type, quality, and expected action, 0.001% by weight or more (hereinafter referred to as “% by weight”), preferably 0.001 to 99%. If the blending amount is less than 0.001%, the effect cannot be expected sufficiently.

  The lifestyle-related disease prevention or amelioration agent of the present invention contains, in addition to the above essential substances, components and additives used for pharmaceuticals and health food preparations as long as they do not impair the effects of the present invention. They can be selected or used in combination.

  Moreover, the dosage form of the lifestyle-related disease preventive agent of this invention is arbitrary, It can mix | blend and use for pharmaceuticals, such as a capsule.

  Specifically, for example, oral compositions (gum, candy, etc.), processed fish paste products such as kamaboko and chikuwa, livestock products such as sausages and ham, Western confectionery, Japanese confectionery, raw noodles, Chinese noodles, boiled noodles, buckwheat noodles Noodles such as sauces, soy sauce, sauce, sugar, honey, dressing, powdered candy, water candy and other seasonings, curry powder, mustard powder, pepper powder and other spices, jam, marmalade, chocolate spread, pickles, sugar beet, Sprinkles or processed vegetables and fruits such as canned and bottled vegetables and fruits, dairy products such as cheese, butter and yogurt, miso soup, soup, fruit juice, vegetable juice, milk drinks, soft drinks, alcoholic beverages, It can be used for general foods and drinks such as health foods.

  The present invention relates to a preventive or ameliorating agent for lifestyle-related diseases such as hypertension, hyperglycemia, hyperlipidemia, decreased blood fluidity, obesity, allergies, etc., or food / beverage products containing a dandelion extract (particularly leaves are preferred) Is to provide.

  In addition, about the method of addition to the lifestyle-related disease preventive agent of this invention, it may add previously, may be added in the middle of manufacture, and should just select suitably in consideration of workability | operativity.

  Hereinafter, test examples and formulation examples will be described, but the present invention is not limited thereto.

Production Example 1
For example, 100 g of a dried product of Fukitan popo leaves was immersed in 1.5 kg of a 30% ethanol solution, extracted at room temperature for 7 days, and then filtered to obtain about 1.0 kg of an extract. This was freeze-dried to obtain 5.1 g of powder.

Production Example 2
For example, 100 g of a dried product of Fukitan popo leaves was immersed in 1.5 kg of a 70% ethanol solution, extracted at room temperature for 7 days, and then filtered to obtain about 1.0 kg of an extract.

Production Example 3
For example, 100 g of a dried product of dandelion flower was immersed in 1.5 kg of a 30% ethanol solution, extracted at room temperature for 7 days, and then filtered to obtain about 1.0 kg of an extract. This was freeze-dried to obtain 4.2 g of a powder.

Test Example 1 Determination of chlorogenic acid and caffeic acid Test method As a standard solution, methanol was added to 3.0 mg of chlorogenic acid (manufactured by Tokyo Chemical Industry) to make 100 mL. In addition, methanol was added to 2.0 mg of caffeic acid (manufactured by Tokyo Chemical Industry) and dissolved to make 100 mL. Next, 1.0 mg of the Fuquitan popo leaf extract obtained in Production Example 1 was taken, adjusted to 10 mL by adding a 50% aqueous methanol solution, and subjected to the test.

Test conditions Measurements were carried out under the following conditions using a high performance liquid chromatograph (manufactured by Shimadzu Corporation), and the results are shown in Table 1. Column: Develosil ODS-HG-5 4.6 × 250 Column temperature: 30 ° C., mobile phase: acetonitrile: 0.05% aqueous acetic acid solution = 20: 80, flow rate: 1.0 mL / min, measurement wavelength: UV 330 nm.

(result)
As shown in Table 1, it was confirmed that the extract of fuchsia poppo leaves of the present invention contains chlorogenic acid content of 0.10% or more and caffeic acid content of 0.3% or more.

Although the example of a food / beverage product formulation is shown below, the example of a formulation may be what was manufactured by the conventional method in manufacture of each product, and showed only the compounding quantity. Further, the present invention is not limited to this.

Formulation Example 1 Tablet Confection Formulation Formulation 1. Fukitane poppo extract (Production Example 1) 2 parts Dried corn starch 50
3. Erythritol 40
4). Citric acid 5
5). Sucrose fatty acid ester 3
6). Perfume appropriate amount 7. Water Appropriate amount [Production method] Components 1 to 4 and 7 are mixed and granulated. Ingredients 5 and 6 are added to the formed granules and compressed. One grain was 1.0 g.

Formulation Example 2 Beverage Formulation Formulation 1. Fukitane poppo extract (Production Example 2) 1 part2. Stevia 0.05
3. Malic acid 5
4). Fragrance 0.1
5). Bring the total amount to 100 with water [Production method] Components 2 and 3 are dissolved in a small amount of water. Components 1 and 4, 5 were then added and mixed.

Formulation Example 3 Tablet formulation Formulation amount 1. Fuquidan Popo Extract (Production Example 1)
10 parts Corn starch 10
3. Purified white sugar 20
4). Carboxymethylcellulose 10
5). Microcrystalline cellulose 35
6). Polyvinylpyrrolidone 5
7). Talc 10
[Production Method] Components 1 to 5 were mixed, and then an aqueous solution of Component 6 was added as a binder and granulated by a conventional method. This was mixed with ingredient 7 as a lubricant and then tableted into 100 mg tablets.

Formulation Example 4 Powder Formulation Formulation 1. Fukitane poppo extract (Production Example 1) 10 parts2. Corn starch 40
3. Microcrystalline cellulose 50
[Production method] The above components were mixed and powdered by a conventional method.

Formulation Example 5 Dressing Formulation Formulation 1. Fuquidan popo extract (Production Example 3) 50 parts Olive oil 23.5
3. Tocopherol-containing vegetable oil extract (tocopherol 20%) 5
4). Soy lecithin (phosphatidylcholine 20%) 0.5
5). Vinegar 10
6). Salt 1
7). Mustard 5
[Manufacturing method] Components 5 to 7 were added to components 1 to 4 and filled into filter paper with stirring to obtain a dressing.

Formulation Example 6 Cooking Oil Formulation Formulation 1. Fukitane poppo extract (Production Example 3) 37.5 parts Lard 30
3. Sesame oil 11.5
4). Tocopherol 5
5). Fractionated lecithin (phosphatidylcholine 70%) 1
[Production method] Components 1 to 4 were heated to be uniform, and then component 5 was added, mixed with stirring, and cooled by packaging to obtain cooking oil.

Test Example 2 Hypertension Suppression Test 12-week-old male, spontaneously hypertensive rat (SHR) was measured for 7 days using a non-invasive blood pressure measuring device (manufactured by Softron Co., Ltd.). Fasted from the day before the test.
On the day of the test, 5 samples of SHR were orally administered to a test group in which the sample of Production Example 1 was suspended at 10 mg / mL in physiological saline using 10 mL / kg and a sonde. In this case, the amount of chlorogenic acid is 15 mg / kg. As control group 1, chlorogenic acid 15 mg / 10 mL / kg was administered, and as control group 2, physiological saline was administered.
The systolic blood pressure before and 6 hours after the administration was measured, and the obtained results were tested by Student's t-test.

(Test results)
Table 2 shows systolic blood pressure before and 6 hours after the start of administration. The blood pressure of the SHR administered with the test group of dandelion extract was significantly lower than that of the control group 2. The effect of the test group was higher than the same amount of chlorogenic acid in the control group 1.

Test Example 3 Blood glucose level improvement test 7-week-old male fasted for 18 hours, ICR mice, 5 mice in each group, and in the test group, the sample of Production Example 1 suspended in 10 mg / mL in physiological saline 10 mL / kg was orally administered using a sonde. In this case, the amount of chlorogenic acid is 15 mg / kg. As control group 1, chlorogenic acid 15 mg / 10 mL / kg was administered, and as control group 2, physiological saline was administered.
Immediately thereafter, 2 g / kg starch was orally administered. Glucose CII test Wako (manufactured by Wako Pure Chemicals: Mutarotase) was used to collect blood from the fundus of the blood collected three times before and 30 minutes after starch loading, and the serum concentration obtained by centrifugation at 5000 rpm for 5 minutes. , Glucose oxidase method). The obtained results were tested by Student's t-test.

(Test results)
As shown in Table 3, at 30 minutes after starch loading, the blood glucose level increased to 275 mg / dL in Control Group 2, whereas it was 182 mg / dL in Control Group 1 and 157 mg / dL in the Test Group, respectively. The rise in blood glucose level was significantly suppressed. The effect of the test group was higher than the same amount of chlorogenic acid in the control group 1.

Test Example 4 Hyperlipidemia Improvement Test Effect on Hyperlipidemia Using Zucker Rat 7-week-old male, Zucker fatty rat, 5 mice in each group, the sample of Production Example 1 in physiological saline at 10 mg / mL The suspension was orally administered at 10 mL / kg using a sonde. In this case, the amount of chlorogenic acid is 15 mg / kg. As control group 1, chlorogenic acid 15 mg / 10 mL / kg was administered, and as control group 2, physiological saline was administered.
Ten days after administration, blood was collected from the heart under ether anesthesia, and serum triglyceride was measured. The obtained results were tested by Student's t-test.

(Test results)
Table 4 shows the amount of serum triglyceride. Serum triglyceride dosed with the Fuquitan popo extract was significantly lowered compared to Control Group 2. This effect was higher than the same amount of chlorogenic acid.

Test Example 5 Anti-obesity test Four-week-old male ICR mice were divided into 5 groups per group and 4 groups so that the average body weights were equal, and were reared for 8 weeks. That is, one group was fed a solid chow (oriental yeast) as a healthy group, and the other three groups were fed the diet shown in Table 5 as a high fat diet group. Further, in the high fat diet group, in the test group, the sample of Production Example 1 suspended in physiological saline at 10 mg / mL was orally administered using a sonde. In this case, the amount of chlorogenic acid is 15 mg / kg. As control group 1, chlorogenic acid 15 mg / 10 mL / kg was administered, and as control group 2, physiological saline was administered.
During the test period, the body weight of each group of mice was measured once a week, and after completion, blood was collected under ether anesthesia, and total cholesterol and triglyceride in the serum were each quantified using Test Wako (manufactured by Wako Pure Chemical Industries). . The results before the start and after 8 weeks were measured, and the obtained results were tested by Student's t-test.

(Test results)
Table 6 shows the body weight, cholesterol, and triglyceride content. When the Fuquitan popo extract was administered, all items significantly decreased compared to the control group 2. This effect was higher than the same amount of chlorogenic acid.

Test Example 6 Blood fluidity test 7-week-old male, spontaneously hypertensive rat (SHR) was orally administered with 10 mL / kg of the sample of Production Example 1 suspended in physiological saline at 10 mL / kg using a sonde. did. In this case, the amount of chlorogenic acid is 15 mg / kg. As control group 1, chlorogenic acid 15 mg / 10 mL / kg was administered, and as control group 2, physiological saline was administered for 28 consecutive days, and then blood fluidity was measured. A microchannel array analyzer (Naka Instruments) was used for the measurement.
The obtained results were tested by Student's t-test.

(Test results)
Table 7 shows the passage time of blood cell components as an index of blood fluidity. The transit time after administration of the Fuquitan popo extract was significantly shorter than that of the control group 2. This effect was higher than the same amount of chlorogenic acid.

Test Example 7 Histamine release inhibition test Mast cells were purified from rats. That is, 20 mL of Most Cell Medium (MCM) was injected into the abdominal cavity of a rat that was lethal to death, and mast cells in the intestinal mucosa were extracted with MCM while massaging for 90 seconds. Rats were laparotomized to recover MCM, cells were washed several times with fresh MCM, then overlaid with 28% BSA solution, left at room temperature for 20 minutes, and the pellet obtained by centrifugation was washed with MCM to obesity A cell suspension was used. A cell suspension was prepared to 1 × 10 ⁵ cells / mL, taken into a test tube, added with a sample or a control substance, and incubated at 37 ° C. for 10 minutes. Further, compound 48/80 having an action of releasing histamine from mast cells was added and incubated, followed by centrifugation after 10 minutes to recover the supernatant free histamine.
The liberated histamine was quantified by o-phthalaldehyde fluorescence measurement, and the obtained results were assayed by Student's t-test.

(Test results)
Table 8 shows the results of the histamine release inhibition test. Application of the dandelion extract significantly reduced histamine release compared to control group 2. This effect was much higher than the same amount of chlorogenic acid.

Test Example 8 Safety test 90-day oral repeated dose toxicity test
10 groups each of 4-week-old male and female Wistar rats, and in the test group, 10 mg / mL of the sample of Production Example 1 suspended in physiological saline was orally administered using a sonde. Administered. As control group 2, physiological saline was administered. This is 90
Repeated for days.
It was carried out every day except for holidays before administration, and the findings were recorded when abnormalities were observed. In addition, the animals were fasted after the final administration. On the day after the final administration, all patients were necropsied to confirm the appearance and the presence or absence of abnormalities in major organs, and the findings were recorded. Further, organ weights were measured for the liver, spleen, pancreas, kidney and adrenal gland. The blood collected at the time of necropsy was subjected to a total of 15 hematological tests including 6 blood images and 18 serum biochemical tests.
The obtained results were each subjected to equivariance analysis of F test, and then the obtained results were tested by Student's t-test.

As a result, there were no deaths during the test period, the body weight steadily changed, and no abnormal findings due to the sample were observed in the general symptoms.
The changes in the measured values observed in the respective hematological and serum biochemical test items were considered to be within physiological variations and not due to sample toxicity. Therefore, it became clear that safety was high.

Test Example 9 Human Use Test Ten capsules containing 1 g of the sample of Production Example 1 were given to 10 male adult subjects with hypertension and hyperlipidemia exceeding the normal range in a regular health check for 1 month. I took it once a day.
On the next day after the end of the administration, breakfast was excluded and blood sugar, triglyceride and the like were measured by weight, body fat percentage, blood pressure, blood sampling.

  Table 9 shows the measurement results of body weight, body fat percentage, blood pressure, blood glucose and triglyceride. There were no subjects who stopped taking the drug for a month, and there were those who complained of constipation and a feeling of fullness of the stomach, but none of the subjects claimed significant physical condition. As for the measurement results, when taking the dandelion extract, all items dropped, and it was considered effective for the prevention and improvement of lifestyle-related diseases.

  It was confirmed that the coltsfoot poppo extract has a lifestyle-related disease prevention effect. That is, the substance of the present invention has an action of suppressing the adverse effects of hypertension, hyperglycemia and hyperlipidemia, decreased blood fluidity, obesity and allergies. Therefore, it can be applied to all forms of food and drink, and is safe to use internally.

Claims (9)

A hypertension preventive or ameliorating agent characterized by containing a squirrel dandelion extract. A hyperglycemia preventive or ameliorating agent characterized by containing a fuquitan popo extract. A hyperlipidemia preventive or ameliorating agent characterized by containing a Fuquitan popo extract. A preventive or ameliorating agent for lowering blood fluidity, characterized by containing a squirrel dandelion extract. An antiobesity agent characterized by containing a licorice poppo extract. An antiallergic agent characterized by containing a licorice poppo extract. A preventive or ameliorating agent for lifestyle-related diseases, characterized by containing a licorice poppo extract. The preventive or ameliorating agent for lifestyle-related diseases according to claim 7, wherein the extraction site of the coltsfoot extract is a leaf. A food or drink comprising the lifestyle-related disease prevention or ameliorating agent according to claim 7 or 8.