JP5160871B2 - Lipid metabolism improver - Google Patents

Description

The present invention relates to a cholesterol concentration increase inhibitor , a neutral fat concentration increase inhibitor, and a pharmaceutical product for suppressing an increase in cholesterol concentration and neutral fat concentration . The cholesterol concentration increase inhibitor , the neutral fat concentration increase inhibitor, and the pharmaceutical agent for suppressing cholesterol concentration and neutral fat concentration increase according to the present invention are particularly those having in vivo neutral fat concentration and cholesterol concentration containing components derived from natural products. It is effective for improvement.

    In recent years, various lifestyle-related diseases caused by high cholesterol have become a problem with westernization of meals typified by high-fat low-fiber diets and lifestyle changes. Among these diseases caused by abnormal lipid metabolism, it has been pointed out that the number of hyperlipidemia patients has been increasing in recent years. Hyperlipidemia refers to a condition in which lipids (fats) in blood, particularly cholesterol and triglycerides (triglycerides) are increased beyond normal values. Since hyperlipidemia has no subjective symptoms, if it is left as it is, arteriosclerosis proceeds and causes heart disease such as angina pectoris and myocardial infarction and cerebral artery disease such as cerebral infarction.

Conventionally, synthetic drugs have been widely used in order to suppress or improve such lipid metabolism abnormalities such as hyperlipidemia. However, since taking medicines obtained by chemical synthesis often involves side effects, taking them for a long time is not always desirable.
Therefore, it is a component derived from natural products, has no risk of side effects and rebound, and can be safely ingested over a long period of time, a cholesterol concentration increase inhibitor , a neutral fat concentration increase inhibitor, a cholesterol concentration and a neutral fat concentration Development of pharmaceuticals for suppressing elevation is desired.

From this point of view, attempts have been made to improve body lipid metabolism with food materials that can be administered on a daily basis. For example, as a lipid metabolism improving agent derived from a natural product, it is contained in one using a limonoid-containing material contained in citrus seeds (see, for example, Patent Document 1), a teraceae plant, a grape plant, or the like. Those using stilbene compounds (for example, Patent Document 2) are known. Attempts to lower blood cholesterol levels include soy protein (for example, see Non-patent Document 1), whey protein (for example, see Non-Patent Document 2), and soy protein hydrolyzate (for example, Non-patent Document). 3), egg yolk phospholipid (for example, see Non-Patent Document 4), and the like. Also, a method of combining lactalbumin, collagen, soy protein or wheat gluten and soy lecithin (for example, see Non-patent Document 5), or a method using a structured soy protein containing soy lecithin (for example, see Non-patent Document 6). Etc.) have been proposed. However, these have problems of requiring a relatively large amount of administration, flavor problems, and storage stability problems such as precipitation during storage when made into a beverage.
JP 2000-72684 A JP 2001-72583 A JP-A-5-176713 Atherosclerosis, 72,115,1988 Agric. Biol. Chem., 55, 813, 1991 J. Nutr., 120,977,1990 Agric. Biol. Chem., 53, 2469, 1989 Nutr. Rep. Int., 28, 621, 1983 Ann. Nutr. Metab., 29, 348 1985

For lifestyle-related diseases such as fatty liver, hyperlipidemia, arteriosclerosis, obesity, etc., blood cholesterol levels and triglyceride levels can be adjusted depending on food ingredients that can be administered daily in addition to medical treatment. which diet Do not lower is essential.
The present invention can improve lipid metabolism by ingesting it, and is useful for the prevention and improvement of lifestyle-related diseases such as fatty liver, hyperlipidemia, arteriosclerosis, obesity, and the like. It is an object of the present invention to provide a cholesterol concentration increase inhibitor and a neutral fat concentration increase inhibitor , which can be administered in an effective manner. Moreover, this invention makes it a subject to provide the pharmaceutical for cholesterol level and a neutral fat concentration rise suppression .

The present inventors have, Toko filtrate which has conducted extensive research on the pharmacological action possessed by the asparagus, A Suparagasu, in particular the擬葉portion of asparagus, is significantly reduced total cholesterol and triglyceride levels in vivo effects Found that there is .

Therefore, the present invention is a cholesterol level elevation inhibitor and a neutral fat level elevation inhibitor characterized by containing asparagus pseudo leaves as an active ingredient. The present invention also relates to a pharmaceutical for suppressing an increase in cholesterol concentration and neutral fat concentration, which contains asparagus pseudo-leaf as an active ingredient.
Furthermore, the present invention includes the use of a lipid metabolism improving agent containing asparagus pseudo-leaf as an active ingredient as a neutral fat concentration increase inhibitor. In addition, the present invention includes the use of a lipid metabolism improving agent containing asparagus pseudo-leaf as an active ingredient as a cholesterol concentration increase inhibitor.

The present invention provides a cholesterol concentration increase inhibitor and a neutral fat concentration increase inhibitor containing asparagus pseudo leaves as an active ingredient, and a cholesterol concentration and neutrality containing asparagus pseudo leaves as an active ingredient. The above problem could be solved by providing a drug for suppressing the increase in fat concentration .

The cholesterol concentration increase inhibitor , the neutral fat concentration increase inhibitor, the cholesterol concentration and the neutral fat concentration increase suppressant of the present invention can suppress the increase in neutral fat concentration and cholesterol concentration by ingesting this. Therefore, it is useful for the prevention and improvement of diseases such as fatty liver, hyperlipidemia, arteriosclerosis and obesity.
In addition, the asparagus pseudo-leaf, which is a raw material for the lipid metabolism improving agent and the like of the present invention, is left to die after the cultivation of the rhizomes and storage roots, or is cut and discarded. It is also a thing. The present invention is also useful in terms of effective utilization of this unused biomass and reduction of waste.

The cholesterol concentration increase inhibitor , the neutral fat concentration increase inhibitor, and the pharmaceutical agent for suppressing cholesterol and neutral fat concentration increase according to the present invention are characterized by containing asparagus pseudo leaves as an active ingredient. .

    Asparagus is a perennial plant of the lily family, and edible is a young stalk that grows from a squamous group, and is made using nutrients (sugar) stored in the storage root in the previous year. There are many roots in the asparagus rhizome. Thick roots are called storage roots and thin roots are called absorption roots. The storage root stores sugar (anabolic products) made on the ground, and the absorption root absorbs nourishing moisture exclusively from the soil. Since the pseudo-leaves where the stalks of the above-ground part changed like leaves in the previous year, the more the young stalks are harvested, the more the stalks that grow well and store a lot of sugar, the young stalks are harvested as food, Leaves the leaves to proliferate pseudo leaves and cultivate underground stems and storage roots, and promote the generation of young stems the following year. From 10 to 30 asparagus stalks are generated from one strain, and the plant height reaches 2m if left untreated. At the end of autumn, it will naturally die or be cut and discarded. Repeat this cycle for about 7-12 years. As described above, the asparagus pseudo-leaf is left to die after the cultivation of the rhizomes and storage roots or is cut and discarded, so that it is unused biomass and waste. Advantages of development and commercialization of primary processed products by using this unused part of asparagus plants, and effective use of unused biomass, environmental conservation by reducing waste, and further increasing the income of asparagus farmers There is.

    Asparagus young stems contain functional substances such as rutin, saponin, fructooligosaccharides and dietary fiber. It is known that some of these substances have an antioxidant action and an antitumor activity. In addition, the rutin content of asparagus pseudo leaves is 100 to 200 times higher than that of ordinary buckwheat. Functionality as a food material is disclosed (WO2006 / 022338).

    As a result of intensive research on the pharmacological action of asparagus, the present inventors have found that the total cholesterol concentration and triglyceride concentration in the living body are prominent in the artificial leaf portion of asparagus with respect to the function of improving lipid metabolism. Has been found to have a lowering effect and significantly improve lipid metabolism.

    The function of improving the lipid metabolism of the asparagus pseudo leaves found by the present inventors is thought to be due to the high rutin content of the asparagus pseudo leaves, and as shown in the following test examples, the asparagus pseudo leaves Feed containing rutin, feed containing rutin, and control feed containing none of pseudo leaves or rutin were administered to rats, and the feed administration group containing pseudo leaves of asparagus was administered feed containing rutin. It was found that the function of improving lipid metabolism was significantly higher than that of the group and the control feed administration group containing neither pseudo leaves nor rutin. The feed administration group containing rutin was similar to the control feed administration group containing neither pseudo leaves nor rutin, and it was found that rutin has no function to improve lipid metabolism. Therefore, it is clear that the function of improving the lipid metabolism of the asparagus simulated leaves is not due to the high rutin content of the asparagus simulated leaves.

That is, the cholesterol concentration increase inhibitor , the neutral fat concentration increase inhibitor, and the pharmaceutical agent for suppressing cholesterol concentration and neutral fat concentration increase according to the present invention are characterized by containing pseudo leaves of asparagus. Specifically, the lipid metabolism improving action is an action of suppressing an increase in serum neutral fat concentration, serum total cholesterol concentration, liver neutral fat concentration, and liver total cholesterol concentration.

In the present invention, asparagus pseudo-leaf is used as an active ingredient of a cholesterol concentration increase inhibitor and a neutral fat concentration increase inhibitor , or as an active ingredient of a drug for suppressing an increase in cholesterol concentration and neutral fat concentration . Asparagus that can be used in the production of lipid metabolism improving agents as described above, the use of artificial leaves of Asparagus officinalis is a large amount of cropping and cultivation techniques Although it is preferable from the viewpoint of accumulation, other types may be used.

The method for producing a liquid preparation for suppressing an increase in cholesterol concentration and neutral fat concentration of the present invention is as follows. Cultivate asparagus officinalis until late summer to remove the adhering soil, soot, etc., and then shred it with a food cutter. Water is added to the shredded product, and the mixture is ground with an electric stone mortar or the like until a predetermined particle size is obtained. The resulting paste-like solution is concentrated with a low-temperature concentrator. Product exhibits a dark green chyme, as is, or cholesterol levels rise suppression solutions other ingredients and blended to the present invention, the neutral fat concentration rise suppressing liquid agent, as well as for cholesterol concentration and triglyceride concentration increased inhibition It can be used as a pharmaceutical product.

Moreover, the manufacturing method of the powdery cholesterol concentration of this invention and a neutral fat concentration raise inhibitor is as follows.
The pseudo leaves chopped with a food cutter are dried using a dryer selected from freeze dryers, vacuum dryers, ventilation dryers, etc., and the resulting dried asparagus pseudo leaves are pulverized according to the application. Powderize with. A fine pulverizer may be used to obtain a powder having a normal particle size, and a turbo mill (Turbo Industry Co., Ltd.) may be used for pulverization. Dry powder, available neat or in the other ingredients and blended with the concentration of cholesterol invention and triglyceride concentrations increased suppression solutions or cholesterol concentration and triglyceride concentration for inhibiting an increase in medicines. Those dried, cholesterol level elevation inhibitor of the present invention, and is better to use as a raw material for triglyceride concentration increase inhibitor or cholesterol concentration and triglyceride concentration increased suppression pharmaceutical products, applications in various fields Is possible.

As the cholesterol level elevation inhibitor and the neutral fat level elevation inhibitor of the present invention, those obtained by chopping pseudo leaves of asparagus, or dried products thereof, those obtained by converting pseudo leaves of asparagus into liquids, or dried products thereof Can be used as they are as the cholesterol concentration increase inhibitor and neutral fat concentration increase inhibitor of the present invention or as a pharmaceutical product for suppressing cholesterol and neutral fat concentration increase .

In addition, the dosage form of the cholesterol concentration elevation inhibitor, the neutral fat concentration elevation inhibitor , and the cholesterol and neutral fat concentration elevation inhibitory drug of the present invention includes powders, tablets, capsules, granules, powders, liquids, etc. Orally. Moreover, these dosage forms can be manufactured by the conventional formulation method known conventionally. For example, it is mixed with a carrier or excipient that is permitted in the production of the preparation and molded. Examples of excipients include lactose, dextrose, cellulose, methylcellulose, starch and the like.

Also, for the lipid metabolism improving food or drink, or a a擬葉asparagus food or drink agent as described above, or those that have been shredded擬葉asparagus, or the dried product, Asparagus pseudo leaves are liquefied or dried, powdered asparagus pseudo leaves are blended into food and drink.

The cholesterol concentration and neutral fat concentration increase inhibitor, and the cholesterol concentration and neutral fat concentration increase suppression pharmaceutical comprising the asparagus pseudoleaf according to the present invention as an active ingredient are excellent cholesterol concentration and medium Prevents lifestyle-related diseases caused by inappropriate eating habits or lack of exercise, and improves metabolic syndrome by suppressing the increase in sex fat concentration . Examples of such lifestyle-related diseases include obesity, hyperlipidemia, hypertension, and diabetes. The cholesterol concentration and neutral fat concentration increase inhibitor according to the present invention , and the cholesterol concentration and neutral fat concentration increase. The inhibitory drug is useful for preventing and ameliorating at least one of obesity, hyperlipidemia, hypertension and diabetes.

In the present invention, the mechanism by which the asparagus pseudo-leaf component has the effect of suppressing the increase in cholesterol concentration and neutral fat concentration is not necessarily clear, but the cholesterol concentration and neutral fat concentration increase suppressing function of the asparagus pseudo-leaf is As mentioned above, it is clear that this is not due to the high rutin content of the asparagus fake leaves.

The doses of the cholesterol concentration, neutral fat concentration increase inhibitor, and the pharmaceutical agent for suppressing cholesterol concentration and neutral fat concentration increase of the present invention vary depending on age, therapeutic effect, pathological condition, etc., and are not particularly limited. What is necessary is just to adjust a compounding quantity etc. so that 1-300g per day, Preferably 2-10g can be ingested.

    Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples. However, these are merely illustrative and the present invention is not limited thereto.

(Preparation of asparagus pseudoleaf puree)
The harvested asparagus pseudo-leaf contaminants were removed, washed, drained, and shredded to 2-3 cm with a food cutter (Slicer OV type, manufactured by Archer). Three times the amount of water was added to the shredded product, and the mixture was ground twice with an electric mill (mass colloider, manufactured by Masuko Sangyo Co., Ltd.) until a predetermined particle size was obtained. The pasty solution was put into a low-temperature concentrator (Evapor, manufactured by Okawara Seisakusho), concentrated to a liquid temperature of 35 ° C. and about Bx15, and further heated at 55 ° C. for 15 minutes to prepare an asparagus pseudo-leaf puree. The product was dark green and contained rutin and sugar suitable for water content. Yield was 150%. This can be used as it is, or filled into a container such as a bottle, can or paper, and used as the cholesterol level elevation inhibitor or neutral fat level elevation inhibitor of the present invention. Also it is incorporated in medicines and as a raw material of cholesterol concentration and triglyceride concentration for inhibiting an increase and Drug. Cryopreservation is also possible.

(Preparation of freeze-dried asparagus pseudo-leaf powder)
The harvested asparagus pseudo-leaf impurities were removed, washed, drained, and shredded to 2 to 3 cm with a food cutter (Slicer OV type, manufactured by Archer). This shredded product was pre-frozen at −40 ° C. and further freeze-dried using a vacuum freeze dryer (manufactured by Kyowa Vacuum Technology Co., Ltd.) at a shelf heating temperature of 30 ° C. and a drying time of 48 hours. Yield was 24%. The dried asparagus pseudo leaves were pulverized with a turbo mill (Turbo Industry Co., Ltd.) to form a powder. This can be used as it is, or filled into a container such as a bottle, can or paper , and used as the cholesterol level elevation inhibitor and the neutral fat level elevation inhibitor of the present invention.

(Preparation of Asparagus pseudo-leaf vacuum dried powder)
The harvested asparagus pseudo-leaf impurities were removed, washed, drained, and shredded to 2 to 3 cm with a food cutter (Slicer OV type, manufactured by Archer). The shredded product was put into a microwave vacuum dryer (manufactured by Nippon Steel Works) and dried for 48 hours under drying conditions of a pressure of 160 torr, an output of 1 KW, and a drying temperature of 60 to 70 ° C. The yield was 22%. The dried asparagus pseudo leaves were pulverized with a fine pulverizer (TV-2 type, manufactured by Tokyo Flour Mill Co., Ltd.) into powder. This can be used as it is, or filled into a container such as a bottle, can, or paper , and used as an inhibitor for increasing cholesterol concentration and an inhibitor for increasing neutral fat concentration of the present invention.

[Test Example 1]
Using the asparagus pseudoleaf powder obtained in Example 2 and commercially available rutin (Sigma) as samples, the effects of improving lipid metabolism were examined using rats.
Eight 18-week-old SD male rats were divided into three test groups (n = 6): a control feed group, a 10% asparagus pseudo-leaf powder feed group, and a 0.1% rutin feed group. , Nippon Claire Co., Ltd.) for 1 week, and then for 4 weeks with the feeds of each formulation shown in Table 1.

    That is, the control feed shown in Table 1 was added to the control feed administration group, the asparagus simulated leaf powder feed administration group was fed with 10% asparagus simulated leaf powder added to the control feed, and the rutin feed administration group was controlled. A feed supplemented with 0.1% rutin was administered to the feed. Feeding water and feed ad libitum, rearing at room temperature 23 ± 1 ° C, humidity 50 ± 5%, 12-hour light-dark cycle (light period; 8: 00-20: 00, dark period; 20: 00-8: 00) Performed under conditions. In the breeding test, the preliminary breeding was conducted for one week, followed by the main breeding for four weeks.

Every day from the start of this breeding, the body weight and feed intake of all rats were measured. In addition, blood was collected from the tail vein on days 0, 7, 21, and 28 from the start of this breeding, and changes in serum total cholesterol and neutral fat concentration over time were measured. At the end of the experiment, the abdomen of the rat was laparotomized under somnopentyl anesthesia, and the perirenal fat and the epididymal fat were removed and their weights were measured. The liver was lyophilized and analyzed for lipid concentration in the liver.
Experimental data are expressed as mean ± standard error (SEM). Statistical processing was performed at 5% significance level by Tukey-kramer's multiple comparison test (p <0.05).

1) Growth curve Fig. 1 shows the growth curve of the group fed with asparagus pseudo-leaf powder-added feed, control feed and rutin-added feed. The asparagus pseudoleaf powder-added feed administration group, control feed administration group, and rutin feed administration group all grew steadily, and there was no decrease in body weight, intake, or feed efficiency due to asparagus pseudoleaf powder intake. Feed efficiency (feed intake / body weight) was a total of 4 weeks, 0.288 ± 0.005 for the control feed group, 0.291 ± 0.006 for the asparagus pseudoleaf powder added feed group, and 0.294 ± 0.005 for the rutin feed group .

2) Organ weight Table 2 shows the results of measurement of the weight of peri-renal fat and epididymal fat.
Ingestion of asparagus pseudoleaf powder showed a decrease in perirenal fat and accessory testicular fat.

3) Measurement result of serum lipid concentration in tail vein blood FIG. 2 shows the measurement result of time-dependent change in serum neutral fat in tail vein blood. The serum triglyceride concentration of tail vein blood in the group administered with asparagus pseudoleaf powder was significantly lower than that in either the control group or rutin group. It turns out that the rise is suppressed.

    In addition, FIG. 3 shows the measurement results of changes in serum total cholesterol concentration of tail vein blood over time. Serum total cholesterol concentration in tail vein blood in the asparagus pseudoleaf powder-added diet group was significantly lower than that in both the control and rutin diet groups, and the asparagus pseudoleaf had serum total cholesterol concentration It turns out that the rise is suppressed.

From the above results, it has been clarified that the asparagus pseudo leaves have an effect of remarkably suppressing an increase in serum neutral fat concentration and serum total cholesterol concentration. Thus, use as the neutral fat concentration increased inhibitor you containing asparagus擬葉is found to have a significant effect. The use as Turkey cholesterol level elevation inhibitor to contain asparagus擬葉is found to have a significant effect.
In addition, the feed administration group which mix | blended rutin was comparable as the control feed administration group, and it turned out that rutin has no function which improves lipid metabolism. Therefore, it is clear that the cholesterol concentration and neutral fat concentration suppression function of the asparagus simulated leaves are not due to the high rutin content of the asparagus simulated leaves.

4) Lipid in the liver The liver was freeze-dried for 4 days with a freeze dryer (VOS / VOC-SD type) and ground in a mortar. Liver powder was stored at −20 ° C. until analysis. Liver lipids were extracted according to the method of Folch et al. The lipid extract was concentrated and dried at 50 ° C. while blowing nitrogen gas using a spray test tube concentrator (EYELA DRY THERMO BATH, MGS-2100, Tokyo Rika). To this was added 2 ml of isopropyl alcohol and sonicated. The neutral fat concentration and total cholesterol concentration in the liver were measured from the solution using a Kinos enzyme kit.
The measurement result of the neutral fat concentration in the liver is shown in FIG. The neutral fat concentration in the liver of the group administered with asparagus pseudoleaf powder was significantly decreased compared to the group administered with the control diet and the group administered with rutin.
The measurement result of the total cholesterol concentration in the liver is shown in FIG. The neutral fat concentration in the liver of the group administered with asparagus pseudoleaf powder was significantly decreased compared to the group administered with the control diet and the group administered with rutin.

From the above test results, it has been clarified that asparagus pseudo-leaf reduces the neutral fat concentration and total cholesterol concentration in the liver.
Therefore, it is clear that the use of the lipid metabolism improving agent containing asparagus pseudo leaves as a neutral fat concentration increase inhibitor has a remarkable effect. Moreover, it is clear that the use of the lipid metabolism improving agent containing asparagus pseudo leaves as a cholesterol concentration increase inhibitor has a remarkable effect.

    In addition, the neutral fat concentration in the liver of the feed administration group containing rutin was similar to that in the control feed administration group, and the total cholesterol concentration in the liver was higher than that in the control diet administration group. This indicates that rutin has no function of improving lipid metabolism, and that the function of improving lipid metabolism of asparagus simulated leaves is not due to the high rutin content of asparagus simulated leaves.

50 g of asparagus pseudo-leaf lyophilized powder obtained in Example 2, 140 g of lactose, 8 g of sugar ester and 2 g of carboxymethylcellulose were mixed and compressed by a compression tablet machine (Fuji Pharmaceutical Machinery Y-5010-Q) (Condition 1 ˜4 tons), a tablet for suppressing an increase in cholesterol concentration and neutral fat concentration of the present invention was produced.

In accordance with the provisions of the 13th revised Japanese Pharmacopoeia Guideline General Formulation “Powder”, 10g of asparagus fake leaf vacuum dried powder obtained in Example 3 was added to 400g of lactose (JP) and 600g of potato starch (JP). Was added and mixed uniformly to produce a powder for suppressing the increase in cholesterol concentration and neutral fat concentration of the present invention.

(Reference Example 1)
40 g of vitamin C or an equivalent mixture of vitamin C and citric acid, 100 g of granulated sugar, and 60 g of an equal mixture of corn starch and lactose were added with 40 g of the asparagus pseudo-leaf dry powder obtained in Example 3 and mixed. Bag packed Me mixtures one bag 1.5g, was prepared stick nutritional health food lipid metabolism improving.

(Reference Example 2)
Sugar 75 g, 60 g citric acid, apple juice 100g, water 794 g, a mixture of asparagus擬葉puree 100g obtained in Example 1 was filled into a container, heat sterilization to, the lipid metabolism improving drinking Manufactured.

The growth curve of the rat which administered asparagus artificial leaf powder addition feed, control feed, and rutin addition feed is shown (test example 1). It is the figure which showed the time-dependent measurement result of the neutral fat density | concentration of tail vein blood (Test Example 1). It is the figure which showed the time-dependent change measurement result of the total cholesterol density | concentration of tail vein blood (Test Example 1). It is the figure which showed the measurement result of the neutral fat density | concentration in a liver (Test Example 1). It is the figure which showed the measurement result of the total cholesterol density | concentration in a liver (Test Example 1).

Claims (3)

A cholesterol concentration increase inhibitor comprising asparagus pseudo leaves as an active ingredient. A neutral fat concentration increase inhibitor comprising asparagus pseudo-leaf as an active ingredient. A medicinal product for suppressing an increase in cholesterol and neutral fat concentrations, comprising asparagus pseudo-leaf as an active ingredient.