JP2006328010A - Lipid metabolism-improving substance containing phlorotannin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new lipid metabolism-improving substance effective for improving lipid metabolisms. <P>SOLUTION: This lipid metabolism-improving substance uses a marine alga, especially phlorotannin derived from Ecklonia kurome. An excellent lipid metabolism-improving substance is obtained by taking the phlorotannin. The phlorotannin can be applied to the prevention and treatment of diseases originating from lipid metabolism abnormality by using the phlorotannin as an active ingredient for drinks, foods or medicines. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a substance for improving lipid metabolism, characterized by containing phlorotannin. More specifically, it contains seaweed-derived florotannins such as eckol, phlorofucofuroeckol A, dieckol, and 8,8'-biequol as active ingredients. It relates to lipid metabolism improving substances. The present invention also relates to foods and drinks and pharmaceuticals containing the lipid metabolism improving substance.

  A group of diseases that develop and progress due to lifestyle habits such as eating habits, exercise habits, rest, smoking, and drinking are collectively called “lifestyle diseases”. Lifestyle-related diseases include non-insulin dependent diabetes (adult diabetes), obesity, hyperlipidemia (excluding familial), hyperuricemia, cardiovascular disease (excluding congenital), colon cancer (familial) Excluding hypertension, squamous cell carcinoma of the lung, chronic bronchitis, emphysema, alcoholic liver disorder, periodontal disease, etc.

Among them, hyperlipidemia (dyslipidemia) is maintained in a state where the lipid concentration in the blood is high, and develops into arteriosclerosis, hypertension, stroke, etc. if the state of abnormal lipid metabolism continues. Care is required for this. As lipids in blood, there are mainly two types of lipids, cholesterol and neutral fat. Cholesterol includes LDL (low density lipoprotein) and HDL (high density lipoprotein). Among them, LDL is also called bad cholesterol because it causes the above lifestyle-related diseases, and HDL is called good cholesterol because it has an action of removing free cholesterol that can cause arteriosclerosis.
In order to improve the symptoms of abnormal lipid metabolism, the use of drugs is of course, but today there is also an increase in health consciousness, and various ideas have been made from daily life to eating habits. Yes. For example, by actively taking in food components that are beneficial to the health of nature from daily life into the body, we will improve lipid metabolism and promote the suppression of fat accumulation in the body, and actively try to prevent lifestyle-related diseases. The style has become established.

  For example, it is known that active intake of dietary fiber, vitamins, polyphenols, and the like has an effect of suppressing fat accumulation and an effect of suppressing neutral fat in serum (Patent Document 1, Non-Patent Document 1).

JP 2003-146898 A Junichi Nagata et al., Journal of Japanese Society of Agricultural Chemistry 2004 (March 28-31, 2004) “Title: Inhibition of Fat Accumulation in Rats by Administration of Polyphenol Material under Obesity-Induced Diet Conditions”

  An object of the present invention is to provide a novel substance for improving lipid metabolism effective for improving lipid metabolism, and a food or medicine containing the substance.

  As a result of searching for a natural material capable of improving lipid metabolism, the present inventors have found that phlorotannin, which is a seaweed-derived component, has an effect of improving lipid metabolism, and has completed the present invention.

  That is, the present invention includes the following inventions as substances effective for improving lipid metabolism.

  1) A lipid metabolism improving substance characterized by containing phlorotannin as an active ingredient.

  2) The lipid metabolism-improving substance according to 1) above, wherein the fluorotannin contains one or more selected from equol, florofcofurecole A, diacor, and 8,8′-bayecol.

  3) The lipid metabolism improving substance according to the above 1) or 2), wherein the fluorotannin is a seaweed-derived fluorotannin.

  4) The lipid metabolism-improving substance according to 3) above, wherein the seaweed-derived fluorotannin is a fluorotannin derived from a seaweed selected from the brown algae chrome, alame, or cajime.

  5) The lipid metabolism improving substance according to 4) above, wherein the seaweed-derived fluorotannin is fluorochrome tannin.

  6) Processed food / beverage products containing the lipid metabolism improving substance according to any one of 1) to 5) above.

  7) A food additive containing the lipid metabolism improving substance according to any one of 1) to 5) above.

  8) A pharmaceutical comprising the lipid metabolism improving substance according to any one of 1) to 5) above.

  By ingesting the lipid metabolism improving substance containing phlorotannin of the present invention and a health food containing this lipid metabolism improving substance, lipid metabolism can be improved on a daily basis, and lifestyle diseases such as hyperlipidemia can be improved. Be expected. In addition, pharmaceuticals containing this lipid metabolism improving substance are expected to be applied to the treatment of lifestyle-related diseases such as hyperlipidemia.

  The lipid metabolism improving substance of the present invention is characterized by containing phlorotannin. As the fluorotannin of the present invention, fluorotannin extracted from brown algae, in particular, chrome is preferable. Fluorotannin extracted from chrome is mainly composed of equol, florofcofurecole A, diacor, and 8,8'-bayecol. The structural formula of each of these fluorotannins is shown in FIG. Each of these fluorotannins can be used singly or appropriately mixed, and is not particularly concerned with the blending ratio and purity.

  Fluorotannin, for example, after methanol extraction of the above dry powder of chrome, concentrate the extract, add methanol, chloroform and water, separate into upper and lower layers, extract the upper layer with ethyl acetate, and extract the ethyl acetate layer. Obtained by concentrating under reduced pressure (crude fluorotannin).

  Crude phlorotannins are phloroglucinol (2%), equol (9%), florofcofurecole A (28%), diacor (24%), 8,8'-bayecol (7%), others (30 %) And separated by chloroform: methanol: water (80: 20: 2, v / v) by silica column chromatography. By collecting the portions that become a single spot on the TLC plate of the separated fractions, equol, Fluorocofloe col A, diacor, and 8,8′-baye col can be isolated.

  The raw material, extraction method and content thereof are not limited as long as the chromate-extracted fluorotannin and the chemical structural formula are similar, and individual fluorotannin can also be obtained by chemical synthesis or the like based on the structural formula shown in FIG. .

  The fluorotannin obtained by the present invention can contribute to the maintenance and improvement of the health of living organisms from mammals of humans and animals to crustaceans by considering an appropriate intake method, amount and frequency.

  For example, in humans, it can be directly applied to health foods, health drinks, processed foods for diet, supplements, or daily dining tables. For companion animals, etc., it can be used as a component of processed foods and beverages for health management of obese animals and aging pets. In addition, in meat production and farmed fish, intake of this component as feed or drinking water can improve meat quality and foodstuffs with abundant fat.

  The food containing the fluorotannin lipid metabolism-improving substance of the present invention includes, as necessary, excipients, extenders, binders, thickeners, emulsifiers, colorants, flavors, food additives, seasonings and the like. Can be mixed. These can be formed as hard capsules, soft capsules such as soft capsules, tablets, or pills, or in the form of powder, granules, bowls, or the like, as necessary.

  Hereinafter, preferred embodiments of the present invention will be described as examples, but the present invention is not limited thereto.

<< Example 1: Fluorotannin Extraction Method / Type / Property / Ingredient >>
Brown algae chrome ( Ecklonia kurome ) was dried and ground. The chrome powder (water content: about 10%, 800 g) was extracted with methanol (2400 mL) by shaking at 90C for 48 hours (90 rev min-1). The extract was concentrated under reduced pressure, methanol (240 mL), chloroform (480 mL) and water (180 mL) were added, and the mixture was separated into an upper layer and a lower layer, and the upper layer was extracted twice with ethyl acetate (300 mL). A crude fluorotannin was obtained by concentrating the ethyl acetate layer under reduced pressure. The yield of crude phlorotannin from chrome powder is about 3%.

  Crude phlorotannins are phloroglucinol (2%), equol (9%), florofcofurecole A (28%), diacor (24%), 8,8'-bayecol (7%), others (30 %) And separated by chloroform: methanol: water (80: 20: 2, v / v) using a silica column chromatography (15 mm id × 150 cm, Wakogel C-300HG, Wako Pure Chemical Industries). The collected fractions on the TLC plate were collected as single spots, which were equol, Fluorocofloe col A, diacor, and 8,8'-baye col.

<< Example 2: Inhibitory effect on liver lipid oxidation in rats fed test phlorotannins >>
Lab MR stock (MR: Nippon Agricultural Industrial Co., Ltd.) was given to all the Wistar rats (140-150 g, male, 8 per group) to be used for the test for 7 days during the preliminary breeding period. Then, add florotannin to processed feed (high fat-containing laboratory MR stock: HLCMR) containing high fat and high cholesterol (cholesterol 1.0%, cholic acid 0.25%, lard 12%) to 0.02, 0.1 or 0.5% feed 14 A group fed freely for a day and a group fed with Fluorotannin to 125, 2000, or 4000 mg / L drinking water (tap water) while using HLCMR as a feed and given freely for 14 days were reared and observed as each test group. HLCMR was given as a positive control group for these test groups, MR was given to the negative control group, and tap water was freely given to the test group for drinking water during the same period. After 14 days in each group, the liver tissue was taken out and subjected to the following test.

  Lipid peroxide (LPO) per liver tissue was extracted with 10 times the amount of chloroform / methanol (2/1), and then triphenylphosphine method (T. Nakamura, H. Maeda Lipids 26, 745-768, 1991). That is, about 1 mg of lipid was reduced with triphenylphosphine in the dark for 30 minutes, and the generated triphenylphosphine oxide was measured by high performance liquid chromatography (HPLC). HPLC conditions were as follows: column Novapack Silica (3.9i.d. × 150 mm), eluent n-hexane / 2-propanol (97: 3), flow rate 1.0 mL / min, absorption wavelength 230 nm.

  As a result, ingestion of HLCMR diet revealed that fat accumulation in the liver tissue became apparent in a short period of time, and the effect on fat metabolism occurred. In such a model, the group that ingested phlorotannin had a significantly lower degree of liver lipid oxidation than the non-intake positive control group, and suppressed deterioration of liver lipid metabolism (FIG. 2).

Example 3: Effect on liver cholesterol in rats fed with phlorotannin
The test was conducted in the same manner as in the rats shown in Example 2, except that the test group was composed of 0.02 or 0.1% in the phlorotannin mixed feed administration system and 125,500 in the drinking water administration system. 4 groups of 2000 or 4000 mg / L were set. After 14 days from the start of administration in each group including the control group, the liver tissue was taken out and subjected to cholesterol level measurement.
A sample for analysis was prepared by extracting 0.5 g of liver by adding 5 mL of methanol and 5 mL of chloroform, dehydrating with anhydrous sodium sulfate and concentrating, and dissolving the above in 1 mL of isopropanol. The measurement was performed by the enzyme method using a commercially available kit (manufactured by Wako Pure Chemical Industries, Ltd.) for the following items.
-Total cholesterol (T-cho): Cholesterol E-Test Wako-Triglyceride (TG): Triglyceride E-Test Wako-HDL cholesterol (HDL): HDL-Cholesterol E-Test Wako-LDL cholesterol (LDL): (T -cho)-(HDL).

As a result, as shown in FIG. 3, the positive control group that did not take phlorotannin was higher in the fat / high cholesterol diet (HLCMR) than in the normal diet (MR) group, T-cho, TG, HDL, LDL. There was a clear effect on liver cholesterol. Under these circumstances, the group in which phlorotannin was added to the HLCMR diet ingested significantly suppressed the increase in LDL levels, which were T-cho in liver tissue and bad cholesterol. A similar inhibitory effect was also observed in the test group ingesting phlorotannin from drinking water. In the case of TG, the average value of the fluorotannin intake group was lower than that of the positive control group and showed a tendency to suppress TG increase. Although HDL, which is regarded as good cholesterol, showed a value close to that of the negative control group in the fluortannin low-dose group, the absolute value was small in all groups and there was no adverse effect due to administration.
Thus, the effect | action which suppresses the rapid deterioration of the cholesterol level in a liver tissue and improves lipid metabolism by ingesting a suitable amount of phlorotannins was confirmed.

<< Example 4: Effect of phlorotannin on rat serum neutral fat >>
Each test group shown in Example 2 was added with a 500 mg / L phlorotannin drinking group. The control group was set and carried out in the same manner as in Example 2. Each rat was subjected to a 12-hour fasting period on the 14th day after the start of administration of the test feed, and blood was collected from the heart and the serum triglyceride (TG) was measured.
Serum triglyceride was measured using an automatic analyzer (Hitachi model 7350) according to the principle of GPO / enzyme method using Nescoat VL II TG reagent.
As a result, in the positive control group, a sharp increase in serum triglyceride level was observed by HLCMR administration. Under such circumstances, the dietary administration of phlorotannin showed an inhibitory effect on serum triglyceride in the 0.5% group. Moreover, each group (125-4000 mg / L) which took phlorotannin as drinking water suppressed the increase in the triglyceride in the serum of a rat in any group. These values were equivalent to the negative control group (FIG. 4).

<< Example 5: Inhibition of hepatopancreas lipid oxidation by phlorotannin-added prawn diet >>
Cultured prawn feed (fish meal 50%, trout 47%, additive 2%, vitamin mix 1%, 0.1%, 0.5% or 1.0% extra) and oral administration for 2 weeks, then prawn hepatic pancreatic lipids Content and LPO were measured.
Hepatopancreas LPO was performed by the lipid peroxide per-tissue measurement method described in Example 3.

As a result, LPO in phlorotannin-incorporated prawn hepatic pancreatic tissue was much smaller than that in the control group, and phlorotannin inhibited hepatopancreatic lipid oxidation (FIG. 5).
The above results indicate that the fluorotannin of Example 1 suppresses the progress of health inhibition (for example, lifestyle-related diseases) associated with high fat and high cholesterol in the living body, that is, effectively suppresses the deterioration of the function of the fat metabolism system. It turned out to be an ingredient.

The figure which shows the structural formula of each phlorotannins. The figure which shows the liver lipid metabolism abnormality (lipid oxidation) inhibitory effect of phlorotannin in the high fat high cholesterol diet rat. The figure which shows the liver cholesterol inhibitory effect of phlorotannin in the high fat high cholesterol diet rat. The figure which shows the serum triglyceride inhibitory effect of the fluoro tannin in a high fat high cholesterol diet rat. The figure which shows the liver lipid oxidation inhibitory effect of phlorotannin administration prawns.

Claims (8)

A lipid metabolism improving substance characterized by containing phlorotannin as an active ingredient. The lipid metabolism-improving substance according to claim 1, wherein the fluorotannin contains one or more selected from equol, florofcophore A, diacor, and 8,8'-bayecol. The lipid metabolism-improving substance according to claim 1 or 2, wherein the fluorotannin is seaweed-derived fluorotannin. 4. The lipid metabolism-improving substance according to claim 3, wherein the seaweed-derived phlorotannin is a phlorotannin derived from a seaweed selected from the brown algae chrome, arame, or cajime. The lipid metabolism-improving substance according to claim 4, wherein the seaweed-derived phlorotannin is phlorotannin derived from chrome. Processed food-drinks containing the lipid metabolism improving substance in any one of Claim 1 to 5. A food additive containing the lipid metabolism improving substance according to any one of claims 1 to 5. A pharmaceutical comprising the lipid metabolism improving substance according to any one of claims 1 to 5.

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