JP5362976B2 - Blood flow improver - Google Patents

Description

The present invention relates to a blood flow improving agent, and more particularly to a blood flow improving agent containing, as an active ingredient, a water-containing ethanol extract of Kawaketsumei administered in a range of 0.01 to 1000 mg / kg body weight of a dry extract per day.

  Blood vessels and blood play a very important role in maintaining the functions of living tissues by supplying oxygen, nutrients, water, hormones, etc. to peripheral tissues, transporting immune cells, discharging waste products, regulating body temperature, etc. Yes. Especially due to a decrease in peripheral circulatory function in capillaries that occupy most of the blood vessels that flow through the body, that is, a decrease in peripheral blood flow, headache, stiff shoulders, dull skin, skin disorders due to decreased metabolism, eyestrain, eye strain, irregular menstruation It is a cause of various symptoms such as coldness and adverse effects on health and beauty, so prevention and improvement are necessary.

  However, this decrease in blood flow is caused by various intricately entangled factors, so the symptoms vary greatly from person to person, and there is currently no effective improvement method for all people, and a new improvement method is desired. .

  Various methods for improving blood flow have been reported so far. For example, gingerol or gingerol contained in ginger extract is disclosed as a composition having an effect of promoting blood circulation to skin cells (Patent Document 1), and similarly as a blood circulation promoting skin external preparation that promotes blood flow in the vicinity of the skin. In addition, it is disclosed that adenosine is effective (Patent Document 2), and further, a rose family Raspberry genus plant (Patent Document 3) is disclosed as a blood circulation promoter having an action of promoting blood circulation of the skin. Further, it is disclosed that cassis anthocyanin is effective as an agent for improving ocular vascular blood flow disorder (Patent Document 4), a prostacyclin production-increasing agent having a vasodilating action by relaxing platelet aggregation and vascular smooth muscle, blood An elderberry extract effective for a flow enhancer or the like is disclosed (Patent Document 5), and an arginine-containing composition for increasing blood flow that reduces blood pressure-lowering side effects and increases blood flow in capillaries is disclosed ( Patent Document 6). Further, Hysop extract of Labiatae plant is disclosed as a blood flow improving agent (Patent Document 7), and an increase in peripheral blood flow is examined for various Chinese medicines (Non-Patent Document 1). However, none of these are sufficient in terms of effects.

  In addition, drugs with vasodilatory action and platelet aggregation inhibitory action, such as prostacyclin derivatives, α receptor blockers, β receptor agonists, calcium antagonists, have side effects such as lowering blood pressure, and are prescribed by doctors. is necessary.

  Furthermore, the chili tincture used as an external preparation for muscle pain, frostbite, frostbite, and hair growth is also known to be effective in promoting blood circulation, but has strong irritation and has a problem in taste. In addition, a hot spring treatment is often performed as a blood circulation promotion, but there is a problem that a sufficient time and cost are required.

  On the other hand, various studies have been made on the leguminous genus Kawara-Ketsumei. In particular, Kawaraketsume, one of the plants belonging to the genus Kawaraketsume, has the scientific name Cassia mimosoides L. It is called var noname Makino or Cassia noname Honda, and is distributed in Japan (Honshu, Shikoku, Kyushu), the Korean Peninsula, and Northeast China. The whole plant is used as a herbal medicine called Sunpens, and is said to have diuretic, tonic and antitussive effects.

  There are various reports on this leguminous genus Kawaroketsume and its components, lipase inhibitory action (Non-patent document 2), anti-obesity action (Non-patent document 3, Non-patent document 4), bone resorption inhibiting action (Patent document 8) Antiallergic action (Patent Document 9), urease inhibitory action (Patent Document 10), whitening action (Patent Document 11), hair restoration action (Patent Document 12), whitening action and antioxidant action (Patent Document 13), active oxygen scavenging action In addition, useful physiological activities such as skin aging inhibition (Patent Document 14) have been reported.

  In addition, there is no report on the effects of oral ingestion on the improvement of blood flow and the improvement of symptoms caused by the improvement of blood flow in the legume family, but there is a description that blood circulation is good with a bathing agent consisting of nine kinds of wild grasses including Yes (Patent Document 15). However, the effect is not objectively shown as data, and it is unclear whether the effect is due to Kawaketsuke.

  On the other hand, a plant belonging to the genus Kawaretsumei is described as a part of a herbal medicine effective for atopic dermatitis and rough skin (Patent Document 16), and other blood flow effects are described (Non-Patent Document 5, Non-Patent Document 6, Non-patent Document Although there is Patent Document 7), none of them is sufficient in terms of safety such as effects and side effects.

  Therefore, it has not yet been reported that leguminous plants are particularly effective for improving blood flow, particularly peripheral circulation function.

JP-A-6-183959 Japanese Patent No. 3798927 Japanese Patent No. 3660833 JP 2007-55903 A JP 2007-39445 A JP 2006-306865 A JP 2006-8575 A JP 2001-72598 A JP 2002-154970 A JP 2003-48844 A Japanese Patent No. 3135943 JP-A-7-101830 JP-A-6-87731 JP-A-8-283172 Japanese Utility Model Publication No. 5-69123 JP 2004-83449 A Pharmaceutical Journal, Vol. 124, No. 6, pp. 365-369, 2004 Bioscience, Biotechnology, and Biochemistry, 56 (9), 1478-1479, 1992. Obesity Research, Vol. 4, No. 3, 217-222, 1998 International Journal of Obesity, 24, 758-764, 2000 Biological & Pharmaceutical Bulletin, 26 (9), 1361-1364, 2003 Chinese Pharmaceutical Journal, 48 (4), 291-302, 1996. Proceedings of the Structure-Activity Relationship Symposium, pp. 234-237, 1987

The object of the present invention is to find an effective blood flow-improving agent containing, as an active ingredient, a water-containing ethanol extract of Kawaroketsume administered in a range of 0.01 to 1000 mg / kg body weight of dry extract per day, and to improve such blood flow. It is to provide a novel blood flow improving agent that can provide an unprecedented sufficient blood flow improving effect by the agent and has no problems in terms of safety, manufacturing cost and palatability.

  The present inventors have conducted a search to solve the above-mentioned problems, and found that leguminous plants of the genus Kawara-Ketsumei, particularly an extract of Kawara-Ketsumei, in particular have a high blood flow-improving effect, and completed the present invention.

That is, the present invention relates to a blood flow improving agent comprising, as an active ingredient, a water-containing ethanol extract of Kawaroketsume administered in a range of 0.01 to 1000 mg / kg body weight of dry extract per day.

  The extract of the genus Papaveraceae of the leguminous plant, which is the active ingredient of the present invention, in particular, the extract of Papaveraceae can improve blood flow, particularly increase peripheral blood flow. Provides a novel use. Kawaraketsumei is widely used as a folklore or tea substitute, and the blood flow-improving agent derived from Kawaroketsumei extract and foods and drinks containing it are also excellent in terms of safety, manufacturing cost and taste. ing.

  The present invention will be described in detail below. Although the blood flow improving agent of the present invention and food and drink containing the same are described, the present invention is not limited thereto.

  The extract used in the present invention is preferably a plant belonging to the genus Legumeaceae that grows in various places throughout the country, in particular, Kawaroketsumei, and all of its parts can be used, but the above-ground part is particularly suitable. The plant of Kawarataketsumei may be extracted as it is, but is preferably extracted by pulverization in order to increase the extraction efficiency.

  Various extraction methods such as solvent extraction and squeezing extraction can be used for extraction, but preferably, solvent extraction can be used. Examples of the solvent used for extraction include, but are not limited to, water, alcohol, ether, acetone, hexane, chloroform, toluene, ethyl acetate, and tetrahydrofuran. One or more of these solvents are selected and used. From the viewpoint of safety, water, methanol, ethanol, acetone and ethyl acetate are preferable, and water and ethanol used for drinking are also preferred. More preferably, it is preferable to use a mixture of water and ethanol, for example, 1 to 99% ethanol aqueous solution, particularly 20 to 80% ethanol aqueous solution.

  In the extraction method, 0.1 to 10 liters, preferably 1 liter, of a solvent is added to 100 g of a pulverized plant body, and the mixture is allowed to stand at room temperature for 1 hour to 1 week, or stirred to increase extraction efficiency. Alternatively, the solvent may be heated.

In the extraction, the insoluble matter and the extract are separated by filtration or sedimentation. Preferably, the insoluble matter is repeatedly extracted in the same manner, and is filtered by an appropriate concentration treatment, for example, by a vacuum concentrator such as an evaporator or by removing the solvent by heating, and then the filtrate is concentrated to obtain a concentrated solution. Further, the concentrated solution can be freeze-dried to obtain a concentrated dried product. Furthermore, the active ingredient may be fractionated using known methods used for separation and extraction of plant components, such as various types of chromatography such as column chromatography, and the purity thereof may be increased. In addition, in the present invention, each of the extraction steps of Kawarataketsumei extract and the above-described purified extract, as well as a commercially available extract of Kawarataketsumei (trade name: Cassianol, manufactured by Lotte Bussan Co., Ltd.) can be used as they are or after being purified. Can do.

  As shown in the Examples, Kawaraketsumei extract has an effect of increasing peripheral blood flow in the entire back of the mouse. By having the above-mentioned action, the Kawaraketsumei extract can be used as an agent for improving a disease caused by a decrease in blood flow, particularly a decrease in peripheral circulation function. In particular, it is effective for blood, which is a decrease in peripheral circulatory function associated with an increase in blood viscosity and an increase in platelet aggregation ability.

  In addition, the method for measuring peripheral blood flow is generally to measure blood flow at one or two points, but this method has a large variation depending on the measurement position and the measurer, and the probe is in contact with the measurement position. In the contact-type measuring machine to be used, there is an influence on the measurement value by stimulation of peripheral blood vessels with a probe or stimulation due to contact. Therefore, in the present invention, it is preferable to use a non-contact type blood flow meter LDI. By using this LDI, it is possible to quantify the peripheral blood flow of the entire back of the mouse, which is not conventional, and it is possible to track changes in the peripheral blood flow of the entire back due to sample administration over time. Therefore, it is possible to measure the peripheral blood flow rate, and therefore, a more effective blood flow improving agent can be detected.

  The Kawaroketsumei extract obtained as described above may be used directly as a blood flow improving agent effective for improving blood flow, but can be administered in various dosage forms. Dissolved or dispersed in a suitable pharmaceutically acceptable liquid carrier, or mixed with or adsorbed to a suitable pharmaceutically acceptable powder carrier, eg capsules, tablets, granules, fine granules It can be used as oral preparations such as suppositories and syrups, and as parenteral preparations such as suppositories and drops. The dose can be appropriately changed according to the symptoms and age of the patient, but may be used in the range of 0.01 to 1000 mg / kg body weight of dried extract per day, and further in the range of 0.1 to 100 mg / kg body weight. Is preferred.

  In addition, the food and drink of the present invention is prepared by adding an extract obtained from the above-mentioned Kawaraketsumei to a normal food and drink, for example, chocolate, candy, jelly, biscuit, chewing gum, ice cream, sorbet, ice confectionery, Sweets such as Japanese confectionery, beverages such as soft drinks, juices, oolong tea, processed meat products, processed fish / fishery products, processed milk / egg products, processed vegetables products, processed cereal products, frozen foods, seasonings, spreads, etc. Can be used. As for the addition amount, it is preferable to add the dry extract in the range of 0.00001 to 10%, preferably 0.0005 to 5% based on the weight with respect to the target food or drink.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

Production example of Kawaraketsumei extract (Production Example 1)
Kawaraketsumei (dried product on the ground) was pulverized, 1 L of 60% ethanol was added to 100 g of the pulverized product, and extracted for a whole day and night with occasional stirring. Insoluble matter was filtered off, the filtrate was concentrated under reduced pressure to distill off ethanol, and a precipitate was recovered from the resulting suspension. The precipitate was washed with water, and the residue was freeze-dried to obtain 3 g of Kawarataketsumei extract.

(Production Example 2)
Kawaraketsumei (dried on the ground) was pulverized, 1 L of methanol was added to 100 g of the pulverized product, and extracted all day and night with occasional stirring at room temperature. Insolubles were filtered off, and the filtrate was concentrated under reduced pressure to obtain 8 g of Kawarataketsumei extract.

(Production Example 3)
Kawaraketsumei (dried product on the ground) was pulverized, 1 L of acetone was added to 100 g of the pulverized product, and extracted all day and night with occasional stirring at room temperature. Insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure and lyophilized to obtain 5 g of Kawarataketsumei extract.

(Production Example 4)
Kawaraketsumei (dried product on the ground) was pulverized, 1 L of water was added to 100 g of the pulverized product, and the mixture was extracted at 70 ° C. for 2 hours. Insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure and then lyophilized to obtain 12 g of Kawarataketsumei extract.

Production examples of comparative plant body extracts (comparative examples)
Ginseng was pulverized, 1 L of 70% ethanol was added to 100 g of the pulverized product, and extracted all day and night with occasional stirring at room temperature. Insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure and lyophilized to obtain 33 g of ginseng extract.

(Test Example 1) Blood flow improvement effect confirmation test sample:
As a test sample, the Kawaroketsumei extract obtained in Production Example 1 and the ginseng extract obtained in Comparative Example were each suspended in 0.01% TWEEN 80, and the sample dosage was 1.0 g / kg body weight, respectively. It was prepared so that it might become.

Experimental animals:
As experimental animals, male ddY mice (body weight 40-50 g) over 40 weeks of age were used. During the period until the experiment, room temperature was 23 ± 1 ° C., relative humidity was 55 ± 5%, light and dark conditions with a cycle of 12 hours, fixed feed (CE-2, Nippon Claire Co., Ltd., Japan) and water were reared freely.

▲ O ▼ Creation of bloody mice:
Mice were treated with betamethasone once a day at a dose of 1.6 mg / kg body weight / day by intramuscular injection into the hind limbs for a total of 7 days.

Administration method:
Using mice that had been brought to a blood state with betamethasone, the administration group suspended the sample in an aqueous 0.01% TWEEN 80 solution and administered it intragastrically using an oral sonde at a dose of 1.0 g / kg body weight. The control group was similarly administered with a 0.01% TWEEN 80 aqueous solution having the same volume. Six mice in each group were administered once a day for 7 days.

Measurement of blood flow:
The back was removed two days before blood flow measurement. Thirty minutes after the final administration of the sample, the mouse was anesthetized with urethane, and the limbs were fixed in the prone position. The change in blood flow for 1 hour was measured with a laser Doppler blood flow imaging apparatus LDI (Moor Instruments, UK) every 15 minutes from 1 hour after the final administration of the sample. The blood flow was calculated as the amount of ml / min / 100 g flowing per minute per 100 g of tissue.

  The measurement results of blood flow in the repeated administration group of each sample (1.0 g / kg) are shown in Table 1 and FIG. Here, the control group (n = 5), the ginseng extract administration group (n = 6), the numerical value is the mean value ± standard error (g / g body weight), and * in the figure is the control of the Kawaraketsumei administration group Significant differences for groups (student T-TEST), p <0.05.

  As can be seen from the results in Table 1 and FIG. 1, a significant increase in blood flow was observed in the repeated administration of the ginseng extract administration group compared to the control group and the ginseng extract administration group of the comparative example.

  The example of the extract by each manufacture example of this invention is given to the following. Each compounding amount is expressed in% by weight, and tablets, powders, capsules, syrups, injections, ointments, chewing gum, candy, tablet confectionery, chocolate, biscuits, ice creams, beverages, yogurt, jam, kamaboko are manufactured according to the standard method. did.

Example 1 (tablets)
Extract of Production Example 1 40.0
Lactose 40.0
Cornstarch 19.0
Sugar ester 1.0
100.0% by weight

Example 2 (tablets)
Extract of Production Example 2 10.0
D-mannitol 35.0
Lactose 40.0
Crystalline cellulose 10.0
Hydroxypropyl cellulose 5.0
100.0% by weight

Example 3 (powder)
Extract of Production Example 1 20.0
Corn starch 25.0
Lactose 55.0
100.0% by weight

Example 4 (capsule)
Extract of Production Example 2 50.0
Lactose 48.0
Magnesium stearate 2.0
100.0% by weight
The above ingredients were mixed uniformly and the mixed powder was filled into hard capsules.

Example 5 (syrup)
Extract of Production Example 4 0.1
Purified water 69.8
Simple syrup 30.0
Calcium carbonate 0.1
100.0% by weight

Example 6 (injection)
Chlorobutanol 0.5
Sodium chloride 0.9
Extract of Production Example 4 0.5
Water for injection
100.0% by weight

Example 7 (ointment)
Extract of Production Example 3 2.0
Glycerin 22.0
Squalane 18.0
Cetyl alcohol 4.5
Magnesium stearate 3.0
Propylene glycol 5.5
Ethanol 7.0
Purified water 38.0
100.0% by weight

Example 8 (chewing gum)
Gum base 22.0
Sugar 67.5
Minamata 7.0
Acidulant 2.0
Fragrance 1.0
Extract of Production Example 1 0.5
100.0% by weight

Example 9 (chewing gum)
Gum base 20.0
Xylitol 75.0
Reduced maltose 2.5
Softener 1.0
Fragrance 0.5
Extract of Production Example 4 1.0
100.0% by weight

Example 10 (candy)
Sugar 50.0
Minamata 35.3
Fragrance 0.5
Water 14.0
Extract of Production Example 2 0.2
100.0% by weight

Example 11 (tablets)
76.6 sugar
Glucose 18.0
Sucrose fatty acid ester 0.2
Fragrance 0.2
Extract of Production Example 1 5.0
100.0% by weight

Example 12 (chocolate)
Sugar 35.6
Cacaomas 18.5
Whole milk powder 18.5
Cocoa butter 17.0
Fragrance 0.2
Emulsifier 0.2
Extract of Production Example 1 10.0
100.0% by weight

Example 13 (chocolate)
Sugar 40.6
Cacao mass 20.0
Whole milk powder 20.0
Cocoa butter 18.0
Fragrance 0.2
Emulsifier 0.2
Extract of Production Example 2 1.0
100.0% by weight

Example 14 (biscuits)
Flour 47.81
Sugar 4.8
Sodium chloride 0.73
Glucose 0.78
Shortening 11.78
Sodium bicarbonate 0.17
Sodium bisulfite 0.16
Rice flour 1.45
Milk powder 1.45
Extract of Production Example 3 0.50
Water residue
100.00% by weight

Example 15 (Ice Cream)
Nonfat dry milk 50.0
Fresh cream 25.0
Sugar 10.0
Egg yolk 10.0
Fragrance 0.1
Extract of Production Example 4 1.0
Water residue
100.0% by weight

Example 16 (Beverage)
Fructose glucose liquid sugar 5.00
Sugar 4.50
Acidulant 1.28
Fragrance 0.20
Extract of Production Example 2 0.02
Water 89.00
100.00% by weight

Example 17 (beverage)
Orange juice 80.0
Sugar 11.7
Acidulant 2.0
Fragrance 1.0
Extract of Production Example 3 0.0005
Water residue
100.0% by weight

Example 18 (Beverage)
Green tea leaf extract 99.85
Ascorbic acid 0.05
Extract of Production Example 4 0.10
100.00% by weight

Example 19 (Beverage)
Oolong tea leaf extract 99.949
Ascorbic acid 0.050
Extract of Production Example 1 0.001
100.000% by weight

Example 20 (yogurt)
Milk 42.0% by weight
Nonfat dry milk 6.0
Sugar 8.0
Agar 0.1
Gelatin 0.1
Lactic acid bacteria 0.005
Fragrance 0.05
Extract of Production Example 4 0.1
Water residue
100.0% by weight

Example 21 (jam)
Pulp 4.0
Sugar 65.0
Kiyosumi juice 25.0
Citric acid 0.5
Extract of Production Example 3 2.0
Water residue
100.0% by weight

Example 22 (Kamaboko)
Surimi of walleye 75.0
Salt 15.0
Seasoning 1.5
Egg white 7.5
Extract of Production Example 2 1.0
100.0% by weight

According to the present invention, it is possible to provide a blood flow improving agent containing a leguminous Kawarataketsu genus plant extract, particularly a Kawataketsumei extract, and a food and drink containing the same. New applications are provided. Further, this extract has been widely used for a long time, such as tea, and is safe and can be used for a long time without side effects.

It is a figure which shows the time-dependent change of the peripheral blood flow volume by the repeated administration of each sample.

Claims (2)

A blood flow improving agent comprising, as an active ingredient, a water-containing ethanol extract of Kawaroketsume administered in a range of 0.01 to 1000 mg / kg body weight of a dry extract per day. The blood flow improving agent according to claim 1, wherein the blood flow improving agent is used for improving peripheral circulation function.

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