JP2008297230A - Cholesterol reducing composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To clarify a new action of a plant of the genus Myrcia, family Myrtaceae, especially Myrcia multiflora. <P>SOLUTION: The cholesterol reducing composition contains a plant of the genus Myrcia, family Myrtaceae, or its extract as an active component. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a cholesterol-lowering composition and a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor.

Pedra Ume Kaa, a plant belonging to the genus Myrchidae, is widely used for diabetes, is commonly known as plant insulin, and is known to ingest bark or leaves as a tea or decoction. Further, aldose reductase inhibitory action (Non-patent Document 1) and active oxygen scavenging action (Patent Document 1) are known.
JP 2000-143482 A Chemical and Pharmaceutical Bulletin (Chem Pharm Bull (Tokyo)). 1998 Jan; 46 (1): 113-9

  An object of the present invention is to clarify a new action of a plant of the genus Myrtia spp., In particular, Pedra ume kaa.

  As a result of studying the pharmacological action of Pedra ume kaa, which is a plant belonging to the genus Milchia, the present inventor has found that this plant or an extract thereof has an inhibitory action on HMG-CoA reductase. It has been found that it has an effect of preventing reduction and prevention of arteriosclerosis, as well as preventing or treating cardiovascular diseases (cerebral infarction, myocardial infarction, stroke) and liver diseases (fatty liver, cirrhosis, liver cancer).

The present invention provides the following cholesterol-lowering composition and HMG-CoA reductase inhibitor.
1． A composition for lowering cholesterol, comprising as an active ingredient a plant of the genus Myrtia spp. Or an extract thereof.
2． Item 2. The composition according to Item 1, wherein the plant belonging to the genus Mirchia is Pedra Ume Kaa.
3． Item 3. The composition according to Item 1 or 2, wherein the extract is a water extract.
Four. Item 4. The composition according to any one of Items 1 to 3, which is used for prevention or treatment of hypercholesterolemia.
Five. Item 5. The composition according to any one of Items 1 to 4, which is a food or oral medicine intended for lowering cholesterol.
6． An HMG-CoA reductase inhibitor comprising, as an active ingredient, a plant of the genus Myrtia spp. Or an extract thereof.
7． Item 7. The HMG-CoA reductase inhibitor according to Item 6, wherein the plant belonging to the genus Myrtia is Pedra Ume Kaa.

  A plant of the genus Myrtiaaceae used in the present invention or an extract thereof, for example, Pedra ume kaa or an extract thereof, is a highly safe material ingested as a tea or decoction in the country of origin. Clarification of the cholesterol lowering action and HMG-CoA reductase inhibitory action of this material has made it possible to provide a safe composition for lowering cholesterol and an HMG-CoA reductase inhibitor.

  In the present invention, the active ingredient having a cholesterol lowering action and an HMG-CoA reductase inhibitory action is derived from a plant belonging to the genus Myrchiaceae, and extracts of these plants are preferably used.

  Examples of the plant belonging to the genus Myrchiaceae include Pedra Ume Kaa, Murta Caberuda, Mapishi, Goyabeira Brava, Pitanga Miuda, and preferably Pedra Ume Kaa.

  Pedra Ume Kaa (scientific names: Myrcia multiflora (Lam.) DC., Myrcia sphaerocarpa DC., Eugenia multiflora Lam., Aulomyrcia sphaerocarpa (DC.) O.Berg, Aulomyrcia caerulescens O.Berg, Aulomyrcia perforata O.Berg etc. Is also a sub-tree that belongs to the Myrtia genus and is distributed in South America. In South America, it is also called Cambui, and there are cases where it is written as pedra, horse, kaa, pedra, umeka, cambuoy, etc. due to differences in pronunciation, but these refer to the same plant and are widely used in the prevention or treatment of diabetes. It is used.

  The extract of the genus Myrtia genus used in the present invention (for example, Pedra, Ume, Kaa) is a plant body such as a leaf, bark (stem or stem), bark, flower, fruit or root of the plant. Or from whole plant / whole plant. In the case where the plant is pedra, ume, or kaa, extracts from leaves and bark are preferably exemplified. The method for producing the extract is not particularly limited, and examples thereof include those extracted at normal temperature or heat using an appropriate extraction solvent. Examples of the extraction solvent include water, hydrous alcohol (eg, hydrous ethanol), lower alcohols having 1 to 4 carbon atoms (eg, methanol, ethanol, n-propanol, isopropanol), ketones such as acetone and methyl ethyl ketone, and ethyl acetate. Examples include esters, polyhydric alcohols (ethylene glycol, 1,3-butylene glycol, propylene glycol, glycerin and the like), ethers such as tetrahydrofuran and diethyl ether, and organic solvents such as hexane. Water, a water-containing solvent, or a water-miscible solvent is preferable, and water, ethanol, and water-containing ethanol are particularly preferable. These solvents may be used alone or in combination of two or more.

  The plant extract may be used as it is in the extracted solution, and may be used after treatment such as concentration, dilution, filtration, etc. if necessary, and the extract may be evaporated to dryness, spray dried, freeze dried, etc. It may be processed and used as a dry product (powder).

  The composition of the present invention is preferably taken as a food or oral medicine. Examples of such preparations include tablets, capsules, granules, powders, drinks, liquids, syrups, chewables, lozenges and the like.

  The composition of the present invention preferably contains 0.001 g to 10 g, more preferably 0.01 to 1 g, still more preferably 0.03 g to 0.3 g per day as the solid content of the extract. Can exert cholesterol-lowering action, HMG-CoA reductase inhibitory action, and the like.

  Preferred subjects for ingesting the composition of the present invention include pets such as humans, cats and dogs, livestock such as cows, pigs, chickens and horses, and mammals such as mice, rats, rabbits and monkeys.

For extraction, for example, low temperature extraction or high temperature extraction may be performed using 0.1 L to 100 g of a plant (leaves, bark, etc.) at a rate of 1 L of solvent. The extraction time is not particularly limited, and may be a short time or a long time.
Examples Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.

Preparation of hot water extract of pedra, ume and kaa
(i) 190 mL of water was added to dried leaves (5 g) of Pedra, Ume, and Kaa, heated for 30 minutes, and extracted with hot water.
(ii) When heated, it was naturally filtered (filter paper No. 1 Advantic) to obtain an extract.
(iii) The extract was freeze-dried to obtain a hot water extract (0.46 g). The yield of pedra / ume / caa on dry leaves was 9.2%.
HMG-CoA reductase activity measurement
(i) Wistar rat liver-derived HMG-CoA reductase was used.
(ii) 100 mM phosphate buffer (pH 7.5, 8 mM glucose-6-phosphate (G-6-P), 1 mM nicotinamide adenine dinucleotide (NADP), 4 mM ethylenediaminetetraacetic acid (EDTA), 2 mM dithiothrei 80 μL of Toll (DTT) and 0.6 U glucose-6-phosphate-dehydrogenase (G-6-PDH) are added, 10 μL of enzyme (28.4 μg / mL) is added, and incubated at 37 ° C. for 15 minutes. did.
(iii) 10 μL of the substrate [ ¹⁴ C] HMG-CoA was added to (ii) to make a total volume of 100 μL (reaction solution A).
(iv) The extract prepared in Reference Example was added to the reaction solution A so that the final test concentrations were about 60 μg / mL, 6 μg / mL, 0.6 μg / mL, and 0.06 μg / mL, respectively.
(v) The reaction was started by adding 2.5 μM [ ¹⁴ C] HMG-CoA substrate to the reaction solution and allowed to react for another 15 minutes. Termination was achieved by adding 5 μL of 1 N HCl (hydrochloric acid).
(vi) The amount of [ ¹⁴ C] mevalonic acid was measured using a liquid scintillation counter (Wallac DSA, 1409).
(vii) The enzyme activity at the time of sample addition was measured by setting the enzyme-free, substrate-free addition as blank (0), enzyme-added, substrate-added, and sample-free addition as 100%, and the inhibitory activity of HMG-CoA reductase was% It showed in. In addition, each measurement was performed twice and the average value was used. Lovastatin was used as a positive control.
(viii) The concentration IC ₅₀ showing 50% inhibitory activity was determined from the measured value.

  The results are shown in Table 1, Table 2, FIG. 1 and FIG.

[実施例１]

[Example 1]

Tea leaf Pedra, ume, and kaa leaves were sterilized as necessary, crushed into strips, chops, powders or granules, then filled into large bags, tea packs, sticks, or three-sided seals and packaged. Moreover, you may add a roasting process after a sterilization process.
[Example 2]

Tablets Pedra Ume Kaa Extract 300.0kg
Lactose 150.0kg
30.0kg starch
Pre-gelled corn starch 15.0kg
Magnesium stearate 1.0kg
First, pedra / ume / caa extract was mixed with lactose, starch, and pre-gelled corn starch, and then granulated by adding an appropriate amount of purified water. The granules were dried and then mixed with magnesium stearate to obtain about 1,000,000 tablets.
[Example 3]

Tea drink 100 grams of Pedra, Ume, and Kaa tea leaves are extracted with 3000 g of ion-exchanged water at 70 ° C. for 5 minutes, and the tea leaves are separated with a 100-mesh stainless steel filter and filtered using filter paper. An extract was obtained. This extract was diluted with ion-exchanged water, 0.3 g of L-ascorbic acid was added per 1000 g, and sodium bicarbonate was added to adjust the pH to 6 to obtain a tea beverage preparation. 500 ml of this tea beverage preparation solution was filled into a plastic bottle at 80 ° C. and sealed to produce a tea beverage.
[Example 4]

Soft capsule The extract of Pedra, Ume, and Kaa obtained in the same manner as in Example 3 was evaporated to dryness and dissolved in ethanol. In this ethanol solution, Actor M-2 (RIKEN Vitamin (RIKEN Vitamin (MCT)) was added. Strain): Fatty acid composition was C8: C10 = 99: 1), and the mixture was stirred for about 1 hour while being kept at about 80 ° C., and then ethanol was removed by concentration under reduced pressure. The insoluble matter was separated by suction filtration to obtain an oil-containing composition. The obtained composition was pressed into a gelatin film by a conventional method to obtain soft capsules.

The measurement result of HMG-CoA reductase inhibitory activity of pedra, ume and kaa is shown. The measurement result of the HMG-CoA reductase inhibitory activity of lovastatin is shown.

Claims (7)

A composition for lowering cholesterol, comprising as an active ingredient a plant of Myrtia spp. Or an extract thereof. 2. The composition according to claim 1, wherein the plant of the genus Myrtia is Pedra ume kaa. The composition according to claim 1 or 2, wherein the extract is a water extract. The composition according to any one of claims 1 to 3, which is used for prevention or treatment of hypercholesterolemia. 5. The composition according to any one of claims 1 to 4, which is a food or oral medicine intended for lowering cholesterol. A 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor comprising, as an active ingredient, a plant belonging to the genus Myrtia spp. The HMG-CoA reductase inhibitor according to claim 6, wherein the plant of the genus Myrtia is Pedra, Ume, Kaa.

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