JP4469406B1 - Blood cholesterol lowering agent - Google Patents

Abstract

The present invention provides a blood cholesterol lowering agent.
A blood cholesterol lowering agent comprising a horse chestnut extract as an active ingredient.
[Selection] Figure 1

Description

  The present invention relates to a blood cholesterol lowering agent.

It is important to prevent obesity so as to be a source of all illness. In particular, as one of obesity, metabolic syndrome (visceral fat syndrome) has recently attracted attention as an indicator of health damage. Metabolic syndrome (visceral fat syndrome) refers to a condition in which at least two of hyperglycemia, hypertension, and lipid abnormalities are combined in addition to visceral fat obesity. When visceral fat accumulates excessively, lifestyle-related diseases such as diabetes, hypertension, and hyperlipidemia are likely to occur. Moreover, arteriosclerosis rapidly progresses by the simultaneous occurrence of the spare groups that have not yet been diagnosed with illness, such as “a little higher blood sugar level” and “a little higher blood pressure”.
According to the 2006 National Nutrition Survey, lipid abnormalities are suspected in 15.8% of men and 16.9% of women, and it is estimated that there are a considerable number of hypercholesterolemia patients as the main cause. It is known that as the total serum cholesterol increases, the relative risk of coronary artery disease increases continuously. For such a condition, not only drug treatment but also treatment by improving lifestyle including meals has been attempted.
Against this background, various proposals have been made in the field of medicine / food (food for specified health use) as a countermeasure against hypercholesterolemia as a risk reduction of coronary artery disease.

  Coumarins contained in horse chestnut, especially esculetin or esculin, are blended in cosmetics and anti-inflammatory skin external preparations. For example, cleansing cosmetics with irritation (Patent Document 1: Japanese Patent Application Laid-Open No. 2007-161727), skin external preparations that improve the skin barrier function (Patent Document 2: Japanese Patent Application Laid-Open No. 2007-161612), and anti-inflammatory activity External preparation for skin (Patent Document 3: Japanese Patent Application Laid-Open No. 2006-28094), Type 2 helper T cell type cytokine inhibitor (Patent Document 4: Japanese Patent Application Laid-Open No. 2004-75619), has an elastase inhibitory action, and is firm to the skin And a skin cosmetic that can retain elasticity (Patent Document 5: Japanese Patent Laid-Open No. 2003-2820), an anti-fading agent (Patent Document 6: Japanese Patent Laid-Open No. 2002-275467), and a melanin production inhibitor. Whitening cosmetics for sensitive skin (Patent Document 7: JP 2000-273019 A) can be mentioned.

The present inventor filed a patent application regarding an anti-obesity agent containing esculin / esculetin (Japanese Patent Application No. 2009-107250), and confirmed the total cholesterol reduction effect of esculin / esculetin alone. Further, in the specification, horse chestnut is cited and described as a plant material containing a high content of esculin / esculetin.
In the present invention, an extract of horse chestnut has been found to have a blood cholesterol lowering effect that is higher than that of the above-mentioned esculin / esculetin alone.

JP 2007-161727 A JP 2007-161612 A JP 2006-28094 A JP 2004-75619 A Japanese Patent Laid-Open No. 2003-2820 JP 2002-275467 A JP 2000-273019 A

  An object of the present invention is to provide a blood cholesterol lowering agent.

That is, the main configuration of the present invention is as follows.
1. An oral blood cholesterol lowering agent comprising an extract from bark of horse chestnut as an active ingredient.
2. 1. Extract is obtained by extraction with water and / or ethanol Oral blood cholesterol-lowering agent described in 1.

The present invention can suppress an increase in blood cholesterol, particularly LDL-cholesterol of bad cholesterol, even if a high-calorie high-fat meal is taken, and the relative risk of coronary artery disease. Can be reduced.
Specifically, the intake of horse chestnut extract can reduce total cholesterol (TCHO), LDL-cholesterol, and free fatty acid (NEFA) as compared to esculin / esculetin alone. The horse chestnut extract can be used as a blood cholesterol lowering agent, medicine, food additive, animal feed additive and the like.

The graph which shows the total cholesterol amount of the 16th week of the mouse | mouth which administered the horse chestnut hot water extract (BW) and the horse chestnut ethanol extract (EtOH) addition high fat diet. The graph which shows the amount of free cholesterol of the 16th week of the mouse | mouth which administered the horse chestnut hot water extract (BW) and the horse chestnut ethanol extract (EtOH) addition high fat diet. The graph which shows the amount of LDL-cholesterol of the 16th week of the mouse | mouth which administered the horse chestnut hot water extract (BW) and the horse chestnut ethanol extract (EtOH) addition high fat diet. The graph which shows the amount of HDL-cholesterol of the 16th week of the mouse | mouth which administered the horse chestnut hot water extract (BW) and the horse chestnut ethanol extract (EtOH) addition high fat diet.

Horse chestnut is native to the Bulgarian region of Greece. Known as the name of Maronnier, it is useful in Europe as a row of trees and park trees. There is a spine on the surface of the horse chestnut but not the fruit of the Japanese horse chestnut. The scientific name is Aesculus hippocastanum, which belongs to the genus Toxinaceae.
The parts used for medicinal purposes are leaves, bark, and seeds, and the uses are used as astringent hemostasis, anti-diarrhea, and expectorant. As a component, coumarin glycosides containing esculin / esculetin are known.
As an Example, the extract which extracted the bark with ethanol or hot water is illustrated.

The present invention can be used as a blood cholesterol lowering agent, food additive, food and pet food, and animal medicine. The dosage form can be formulated into an arbitrary form together with an auxiliary agent by a known method and administered orally. It can be administered as a capsule or tablet, granule, fine granule, powder, or liquid.
The dose may vary depending on the administration method and the age, medical condition, general condition, etc. of the patient, but from the results of animal tests, 1 to 1,000 mg as an active ingredient per day is usually appropriate for 1 kg of body weight in adults.

The blood cholesterol-lowering agent of the present invention can be incorporated into general foods and health foods, and can also be used as a component of food additives. The food to be blended is not particularly limited, for example, bakery food such as bread, confectionery bread, pie, Danish, donut, cake, noodles such as udon, soba, Chinese noodles, yakisoba, pasta, fries such as tempura, croquette, curry, Examples include sauces such as stew and dressing, sprinkles, kneaded products such as kamaboko, beverages such as juice, and confectionery such as snacks, rice cakes, rice cakes, and gums.
Suitable for pets as feed for mammals such as dogs, cats, hamsters and squirrels. The form of the pet food of the present invention is not particularly limited, and examples thereof include dry type, wet type, semi-moist type, biscuit type, sausage type, jerky type, powder, granule, capsule and the like.

[Evaluation using C57BL / 6CrSlc mice]
Serum biochemistry of C57BL / 6CrSlc mice was performed with high-fat diet mixed with horse chestnut extract.

<High fat feed preparation>
The high fat diet was prepared with the components shown below by further adding fat components based on oriental yeast powder feed (MF powder feed) used for normal breeding.

<Experimental animals>
A total of 25 male 7-week-old C57BL / 6CrSlc mice, preliminarily raised for 7 days, are used for the experiment. Mice are kept in a breeding room (lighting time 12 hours) at room temperature 23 ± 5 ° C. and relative humidity 55 ± 15% throughout the preliminary breeding period and experimental period.
5 mice / cage, normal diet (ND) supplemented twice a week, high-fat diet (HFD) with the same daily consumption (2-3 g / mouse / day) of the vehicle administration group as all drugs The administration group was given and HFD was replenished daily. Drinking water was given tap water freely with a water bottle.

<Trial manufacture of hot spring extract of horse chestnut>
1 kg of dried and ground bark of the horse chestnut was immersed in 15 liters of water and heated for 1 hour. It was then filtered and the residue treated again with 15 liters of water. The extracts obtained by the above two treatments were combined and concentrated under reduced pressure to obtain a concentrated solution. This concentrated solution was dried under reduced pressure to obtain 228 g of a hot water extract of horse chestnut.

<Trial production of 90% ethanol extract of horse chestnut>
1 kg of a dry pulverized product of a horse chestnut bark was immersed in 15 liters of 90 vol% ethanol and heated under reflux for 1 hour. It was then filtered and the residue treated again with 15 liters of 90% by volume ethanol. The extracts obtained by the above two treatments were combined and concentrated under reduced pressure to obtain a concentrated solution. This concentrated solution was dried under reduced pressure to obtain 180 g of a horse chestnut 90% ethanol extract.
When the amounts of esculin and esculetin contained in the horse chestnut extract were measured, the results shown in Table 2 were obtained. This is because the amount of esculin contained in 50 mg of hot water extract of horse chestnut is about 10.0 mg, the amount of esculetin is about 0.17 mg, and the amount of esculin contained in 50 mg of horse chestnut ethanol extract is about 9.4 mg, The amount of esculetin is about 0.4 mg.

<Drugs to be administered>
A hot water extract of horse chestnut (BW) and an ethanol extract of horse chestnut (EtOH) were orally administered every other day at 50 mg / kg. Each drug was dissolved in 5% Cremophor® EL and administered orally. Further, as a vehicle group, a 5% Cremophor aqueous solution containing no drug was orally administered in the same manner.

<Biochemical testing>
Whole blood was collected from mice 16 weeks after the start of the experiment, and the following items shown in Table 3 were examined. Serum total cholesterol (T-CHO), free cholesterol (F-CHO), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) were measured. The measurement was performed using a Hitachi 7180 type automatic analyzer.
The results are shown in FIGS. The obtained value is t-tested to obtain the significance (P value) and is expressed as * when p <0.05, ** when p <0.01, and NS when p> 0.05.

(result)
Total cholesterol, free cholesterol, and LDL- of mice administered with high fat diet supplemented with horse radish hot water extract (BW) and horse chestnut ethanol extract (EtOH) compared to mouse vehicle (HFD) fed only with high fat diet It can be seen that cholesterol is significantly suppressed. On the other hand, no significant difference was observed for HDL-cholesterol, which is good cholesterol.
In a prior application (Japanese Patent Application No. 2009-107250) related to the present applicant, a decrease in total cholesterol was observed in mice administered with high-fat diet containing esculin and esculetin (ECL (HFD)). A decrease in total cholesterol has been confirmed as a result of administration of esculin or esculetin at 30 mg / kg. On the other hand, as described above, 50 mg of the horse chestnut extract of the present invention contains 10 mg of esculin and 0.3 mg of esculetin, so in comparison with the findings of the previous application, It was confirmed that the product exhibited a total cholesterol lowering effect at 1/3 in terms of esculin and 1/100 in terms of esculetin.
More specifically, LDL-cholesterol, which is a bad cholesterol, was significantly lower than that of a high-fat diet-added mouse, and no difference was found for HDL cholesterol, which was a good cholesterol. In addition, the present inventors found that the hot water extract of horse chestnut hot water (BW) and the extract of horse chestnut ethanol (EtOH) of the present invention have an effect of lowering cholesterol than esculin / esculetin alone.
Therefore, it can be seen that the continuous intake of the horse chestnut hot water extract (BW) and / or the horse chestnut ethanol extract (EtOH) has an effect of reducing blood cholesterol.

The example of prescription using the horse chestnut extract of this invention is shown below.

Formulation Example 1
[Capsule]
Composition Horse chestnut extract (ethanol extraction) ... 100mg
Beeswax 10mg
Grape seed oil… 110mg
The above ingredients were mixed and filled into a capsule base mixed with gelatin and glycerin to obtain soft capsules.

Formulation example 2
[tablet]
Composition Horse chestnut extract (ethanol extraction)… 150mg
Cellulose… 80mg
Starch ... 20mg
Sucrose fatty acid ester 2mg

The above components were mixed and tableted to obtain tablets.

Formulation Example 3
[Beverages]
(Composition) (Composition: Mass%)
Fructose butter sugar liquid sugar 5.00
Citric acid 10.4
L-ascorbic acid 0.20
Perfume 0.02
Dye 0.10
Horse chestnut extract (ethanol extraction) 1.00
Water 82.28

Claims (2)

An oral blood cholesterol lowering agent comprising an extract from bark of horse chestnut as an active ingredient. The oral blood cholesterol lowering agent according to claim 1, wherein the extract is obtained by extraction treatment with water and / or ethanol.

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