JPH07118159A - Hypolipemic agent - Google Patents

Abstract

PURPOSE:To provide an agent for suppressing neutral fat in blood or an agent for suppressing neutral fat and phospholipid in blood and easily usable without problem of side actions. CONSTITUTION:Common oil seeds such as soybean and sesame are pressed and/or extracted with an organic solvent. After separating the gummy component or dregs from the obtained stock oil, the oil is treated with a lower alcohol such as ethanol optionally in combination with an adsorbent such as silica gel to obtain a fractionated glycolipid containing steryl glycoside and/or its acylation product or their concentrated products. The glycolipid fraction or its concentrate is compounded to a conventional raw materials to obtain foods, drinks, animal feeds or pharmaceuticals.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a blood lipid lowering agent containing glycolipid obtained from oil seed as an active ingredient, more specifically, a blood neutral lipid lowering agent, or a blood neutral lipid and a blood phospholipid. Regarding a lowering agent.

[0002]

2. Description of the Related Art In order to produce oils and fats from oil seeds such as soybean, rapeseed and sesame, the seeds are usually pressed and / or extracted with an organic solvent such as hexane to obtain crude oil, which is stored. Let it stand in a tank to precipitate a so-called sediment, or blow water or steam to hydrate and agglomerate the gum, and after separating them, if necessary, perform purification treatments such as deoxidation, decolorization and deodorization. It is processed into oil and fat products.

Here, the gum is also called an oil slag, and generally has a water content of 50 to 80% by weight and an oil content of 20 to 50% by weight. Of these, the oil is a neutral lipid containing triglyceride as a main component, fatty acid, and lecithin. Includes phospholipids and glycolipids commonly referred to as. Such gums have water content removed to give a paste-like lecithin, and further lecithin can be concentrated using a solvent such as acetone or ethanol, or its individual components, namely phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, etc. Purified to high purity and used as an emulsifier in the fields of food, cosmetics, agricultural chemicals, pharmaceuticals, etc. The glycerides and fatty acids separated at this time are also reused in oil-related products. However, glycolipid-based components such as steryl glycosides and acylated steryl glycosides have not yet been effectively utilized industrially.

On the other hand, when the crude oil is allowed to stand, the sediment, which is a precipitate, is usually formed in the sesame oil production process.
Separated from sesame oil and disposed of. It is known that this ori contains a glycolipid mainly composed of steryl glycoside and its acylated product.

By the way, cholesterol, neutral lipids and phospholipids are generally known as constituent indices of blood lipids. Of these, blood neutral lipids have not been considered until recently as an independent risk factor for arteriosclerosis. However, when looking at the serum lipids of patients with myocardial infarction, cerebral infarction, and peripheral arteriosclerosis obliterans, 30% of patients have hypercholesterolemia (serum cholesterol concentration: 220 mg / ml or more).
Rarely, rather, about 40% is associated with hypertriglyceridemia or hypoHDLemia. Also, diabetes and high blood pressure,
From the results of genetic studies of cardiovascular diseases, hypertriglyceridemia has been cited as a condition for the frequent occurrence of coronary artery disease ("Ayumi of Medicine", Volume 164, pp. 832-846, 19).
1993).

Therefore, it is expected to prevent arteriosclerosis by reducing the blood neutral lipid concentration. Fibrates and nicotinic acid preparations are used as agents for lowering blood neutral lipids. However, administration of these drugs causes side effects such as gastrointestinal disorders and liver disorders (Yamamoto, A., Coronary, Vol. 4, 289-299).
Page, 1987), so it cannot be said that it can be used easily and easily. In addition, blood phospholipid concentration is also a factor to be noted in relation to hyperlipidemia.

[0007]

Therefore, an object of the present invention is to use a general-purpose oil seed component, a hypolipidemic agent for blood, which has few side effects and is simple and can be used daily.
More specifically, it is to provide a blood neutral lipid lowering agent or a blood neutral lipid and blood phospholipid lowering agent.

[0008]

[Means for Solving the Problems] To achieve the above object, the present inventors have conducted extensive studies on the relationship between various components in oil seeds and the blood lipid lowering effect, and completed the present invention. It was That is, the present invention is a blood neutral lipid lowering agent or a blood neutral lipid lowering agent containing a glycolipid as an active ingredient, which is obtained by fractionating gums or ori generated in the step of producing fats and oils from oil seeds with a lower alcohol. It is a sex lipid and a blood phospholipid lowering agent. In the following description of the present invention, blood neutral lipids, or blood neutral lipids and blood phospholipids may be simply abbreviated as blood lipids.

The oil seed used as the starting material of the present invention is a general-purpose raw material for producing fats and oils such as soybean, rapeseed, corn, sesame, cottonseed, sunflower, safflower, flax, palm and the like. preferable. With or without roasting treatment, such oil seeds are pressed and / or solvent-extracted to produce crude oil, which is then allowed to stand for 2 to 10 days at, for example, 20 to 50 ° C., causing sedimentation. Alternatively, when water or steam is blown into the crude oil in an amount of 1 to 10% by weight, the gum aggregates and precipitates. Then, in the present invention,
The active ingredient in the present invention is fractionated and concentrated from the gum or agglomerate.

When the gum is used, first, water is removed from it using a suitable drying means, and then a neutral lipid, a fatty acid, a coloring substance composed of a glyceride such as triglyceride or diglyceride in a ketone organic solvent such as acetone is added. The odorous component and the like are dissolved and separated to obtain a lecithin-based polar lipid precipitate as an insoluble matter. The precipitate contains lecithin, which is a phospholipid such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidic acid and their lyso forms, as well as the glycolipid according to the present invention.

Next, the dried product of the polar lipid is dissolved in, for example, hexane and the silica gel column (Wako gel C-100) is used.
First, the lecithin component is first eluted with hexane as an elution solvent, and then the glycolipid component is eluted with a lower alcohol such as methanol or ethanol as an elution solvent. The glycolipid fraction obtained here is sitosterol,
Campesterol, sterols such as stigmasterol, and glucose, galactose, stachyose, steryl glycosides in which sugars such as raffinose are bound,
And an acylated product thereof, that is, a main component containing a 6-position hydroxyl group of a sugar chain and a palmitic acid, oleic acid, linoleic acid, or the like, through an ester bond. If necessary, the glycolipid fraction was dissolved in the new lower alcohol and subjected to the same silica gel column chromatography again to give a fraction in which the acylated steryl glycoside was further concentrated, and a free steryl glycoside. Can be divided into more concentrated categories.

When the aforesaid is used, it is dispersed in, for example, hexane to separate a hexane-insoluble fraction from which neutral lipids and the like have been removed, and then further dispersed in a lower alcohol to obtain a soluble fraction, or hexane. / Lower alcohol =
Dispersed or dissolved in 1/9 to 9/1 to fractionate to obtain a lower alcohol-soluble section, or dispersed in lower alcohol to obtain a soluble section, and lower alcohol is removed from any of these to obtain a glycolipid as a main component. The fractionated product can be obtained. Here, methanol or ethanol is preferable as the lower alcohol from the viewpoint of solubility, and if necessary, the fractionation efficiency can be increased by heating the fractionation operation to 40 to 50 ° C. and then cooling.

The glycolipid fraction thus obtained can be obtained by repeating the solvent fractionation using the above lower alcohol, or by dissolving it in a lower alcohol and subjecting it to silica gel column chromatography in the same manner as in the case of using a gum. , Other ori components and free steryl glycoside enriched fraction can be separated.

In the present invention, a blood lipid lowering agent containing the glycolipid fractionated as described above as an active ingredient is developed. That is, a glycolipid fraction containing at least 0.1% by weight or more of steryl glycoside and / or an acylated product thereof, or a concentrate of each glycolipid, alone or added to a known food material, It is used as an animal feed by mixing it with a raw material for feed, or as a pharmaceutical preparation together with components and carriers suitable for pharmaceutical use. Here, if the glycolipid component in the fraction to be blended is less than 0.1% by weight, a large amount of the fraction must be blended in order to exert the blood lipid lowering effect which is the object of the present invention. Not to mention, and other components mixed at that time may suppress the effect of the present invention.

The blood lipid-lowering agent of the present invention, in foods and drinks and animal feeds, contains a fraction containing glycolipid or a concentrate of each glycolipid in an amount of about 0.5 to 10% by weight, And a steryl glycoside and / or an acylated product in an amount of 0.05 to 5
If it is blended in an amount of about% by weight, the effect is sufficiently exerted. Further, as a pharmaceutical preparation, known binders, excipients, etc. are added and can be orally taken in the form of powder, granules, tablets or capsules by a conventional method, or a commonly used stabilizer, auxiliary agent. It is also possible to administer parenterally without injection, etc. In this case, the amount of the glycolipid-containing fraction or concentrate according to the present invention is about 0.1 to 50% by weight, and the amount of steryl glycoside and / or its acylated product is 0.1 to 50% by weight.
It is about 10% by weight. The dose can be appropriately changed depending on the symptom, but is about 10 to 100 mg / kg / day.

[0016]

EXAMPLES In the following reference examples and examples,% is based on weight. [Reference Example 1 Preparation of Soybean Lecithin and Glycolipid Fractions] The soybean gum extracted from the soybean with hexane was dried to remove gum, and 10 kg of acetone was added to 1 kg of the dried product. After stirring, the precipitate was collected and acetone was distilled off under reduced pressure to obtain 800 g of acetone insoluble matter. Then, 600 g of this acetone insoluble matter was dissolved in 7 liters of hexane and the silica gel column (Wako gel C-100, 1.2
kg)), 2 liters of hexane were flowed to collect the elution fractions, and the solvent was distilled off under reduced pressure to obtain a lecithin fraction F1. Further, 10 liters of ethanol is poured to collect the elution sections,
The solvent was distilled off under reduced pressure to obtain glycolipid fraction F2. The yields of F1 and F2 were 540 g and 55 g, respectively. The composition of F1 was analyzed by high performance liquid chromatography to find that phosphatidylcholine 30%, phosphatidylethanolamine 26% and phosphatidylinositol 16% were the main components, and the composition of F2 was analyzed by high performance liquid chromatography. , Steryl glycoside 14%, acylated steryl glycoside 40%, and other 46%.

500 g of F1 was dispersed in 10 times volume of ethanol and fractionated into an ethanol-soluble section and an ethanol-insoluble section. The yield after the solvent was distilled off was ethanol-soluble fraction (F1-1): 150 g, ethanol-insoluble fraction (F1-2): 350 g, and when the composition of each was analyzed, F1-1 was phosphatidylethanolamine. Two
The lecithin concentrate was 6% and phosphatidylinositol 28% as the main component, and F1-2 was the lecithin concentrate that was 57% phosphatidylcholine as the main component.

On the other hand, 50 g of the above-mentioned F2 was added to ethanol 50
Dissolve it in 0 ml and apply it to a silica gel column (Wako gel C-100, 1
(2 kg), and ethanol is flowed to the first elution section 2 liters (F2-1) and the subsequent elution section 2 liters (F2-
2), and 2 liters of the subsequent elution fraction (F2-3) was collected. The solvent was distilled off from each section, the yield was determined, and the composition was analyzed. As a result, F2-1 was a glycolipid concentrate having a yield of 30 g and an acylated steryl glycoside of 88% as a main component, and F2-3 was The yield was 18 g, which was a glycolipid concentrate containing 92% of free steryl glycoside as a main component.

Example 1 Four-week-old male SD rats 7
One group of animals was used, the soybean oil-added section containing 10% soybean oil was used as a control group, and 5% of this soybean oil was replaced with the same amount of other components as shown below to obtain test groups. Lecithin fraction addition section: Lecithin fraction F1 described in Reference Example 1, glycolipid fraction addition section: Glycolipid fraction F2 described in Reference Example 1, lecithin concentrate (1) addition section: Reference Ethanol-soluble section F1-1 described in Example 1, lecithin concentrate (2) addition section: Ethanol-insoluble section F1-2 described in Reference Example 1. Table 1 shows the feed composition of each test plot.

[0020]

[Table 1] Note 1) Vitamin mix and mineral mix: AIN-762 2) to 5) manufactured by Clea Japan Co., Ltd .: See Reference Example 1.

A breeding test was carried out for 3 weeks with free intake of water and feed, and after the test, neutral lipids, total cholesterol and phospholipids in blood and liver of rats in each group were measured. The results are shown in Tables 2 and 3. The blood neutral lipid, total cholesterol and phospholipid concentrations in the glycolipid fraction-added group were significantly lower than those in the group containing only soybean oil (control group). No significant difference was found in the blood neutral lipid concentrations in the lecithin fraction-added group and the lecithin concentrate (2) -added group compared with the group containing only soybean oil (control group), and the lecithin concentrate (1) was added. On the contrary, in the plot, a high value was shown (Table 2). Neutral lipid concentration in the liver of the lecithin fraction addition group, the glycolipid fraction addition group, the lecithin concentrate (1) addition group and the lecithin concentrate (2) addition group was the soybean oil only group (control group) The value was significantly lower than that of (Table 3). From these results, it was clarified that the concentration of neutral lipid in blood was lowered by the addition of the glycolipid fraction containing steryl glycoside and its acyl compound.

[0022]

[Table 2] Note) Each value is shown as the average value ± standard error. *: The risk rate is 5% or less, which is significantly different from the control group.

[0023]

[Table 3] Note) Same as Table 2

[Reference Example 2 Preparation of Sesame Glycolipid Fraction and Concentrate] Crude oil obtained by roasting and pressing sesame seeds by a conventional method was allowed to stand in a storage tank at 40 to 25 ° C. for 10 days, After separating the deposited precipitate (ori) by filtration, 50 kg of this 10 kg
Washing was repeated 3 times with 50 liters of ethanol at -60 ° C. Oils and fats and insoluble materials were removed, and ethanol was distilled off from the collected ethanol layer under reduced pressure to obtain a solid content of 800 g. This was dissolved in 5 liters of hexane and subjected to a silica gel column (Wako gel C-100) in the same manner as described in Reference Example 1 to elute 2 liters of hexane (lecithin fraction), followed by ethanol. It was divided into elution fractions (glycolipid fraction, F3) when 15 liters were allowed to flow down. The yield of F3 was 600 g, and as a result of composition analysis by high performance liquid chromatography, steryl glycoside 85 was obtained.
%, Acylated steryl glycoside 5%, 1,28-octacosadicarboxylic acid 8%, and other 2%.

Then, 500 g of F3 was dissolved in 5 liters of ethanol and the mixture was applied to the same silica gel column, and ethanol was allowed to flow down, and the elution fractions were divided into 3 liters (2 liters).
3-1, F3-2 and F3-3) were collected. The solvent was distilled off from each section, and the yield was measured and the composition was analyzed. As a result, F3-1 was a yield of 4 g, a glycolipid concentrate containing 93% of acylated steryl glycoside as a main component, and F3-3 was a yield. It was a glycolipid concentrate of 441 g, 95% free steryl glycoside.

Example 2 Four-week-old male SD rats 7
One group of animals was used. Regarding the feed composition, the soybean oil-added section used in Example 1 shown in Table 1 was used as a control group, and 1% of this soybean oil was replaced with the same amount of other components shown below, and each group was used as a test group. Glycolipid fraction addition group: Glycolipid fraction F3 described in Reference Example 2, glycolipid concentrate (1) addition group: F3-based on the acylated steryl glycoside described in Reference Example 2
1, glycolipid concentrate (2) addition group: F3-3 containing steryl glycoside as described in Reference Example 2 as a main component.

In the same manner as in Example 1, water and feed were freely ingested and a breeding test was carried out for 3 weeks, and neutral lipids, total cholesterol and phospholipids in blood and liver of each group of rats were measured. The results are shown in Tables 4 and 5. From the experimental results of Example 2, also, when the glycolipid fraction and the concentrate were added to the feed,
It was revealed that the neutral lipid and phospholipid levels in blood decreased. Also in the liver, the concentration of neutral lipids was significantly lower than that of the soybean oil-added group.

[0028]

[Table 4] Note) Each value is shown as the average value ± standard error. *: The risk rate is 5% or less, which is significantly different from the control group. 1) The feed composition is the same as the soybean oil-added section in Table 1 2) 1% of the glycolipid fraction F3 of Reference Example 2 is added 3) 1% of the glycolipid concentrate F3-1 of Reference Example 2 is added 4) Reference Add 1% of glycolipid concentrate F3-3 of Example 2

[0029]

[Table 5] Note) Same as Table 4

[0030]

INDUSTRIAL APPLICABILITY According to the present invention, the gum or ori generated in the step of producing fats and oils from general-purpose oil seeds such as soybean and sesame is fractionated with a lower alcohol such as methanol and ethanol to obtain. Blood lipid lowering agent, or blood neutral lipid and blood phospholipid lowering agent containing a glycolipid fraction containing a steryl glycoside and / or an acylated product thereof, or a concentrate thereof as an active ingredient Will be provided. This blood lipid lowering agent can be used alone or can be blended with known raw materials to form foods and drinks, animal feeds or pharmaceutical preparations, and can be easily used without fear of side effects.

Claims (4)

[Claims] 1. A blood neutral lipid lowering agent or blood containing a glycolipid as an active ingredient, which is obtained by fractionating gum or ori produced in the step of producing oils and fats from oil seeds with a lower alcohol. Neutral lipid and blood phospholipid lowering agent. 2. The blood lipid lowering agent according to claim 1, wherein the oil seed is soybean or sesame. 3. The blood lipid lowering agent according to claim 1, wherein the lower alcohol is methanol or ethanol. 4. The blood lipid lowering agent according to claim 1, wherein the glycolipid is a steryl glycoside and / or an acylated steryl glycoside.