JP5232979B2 - Cholesterol reducing agent - Google Patents

Description

  The present invention relates to a cholesterol reducing agent.

  Cholesterol is either contained in food and taken by meal, or is synthesized in the body. Cholesterol is a component that becomes a material for cell membranes and sex hormones, but if it increases too much in the body due to overdose, it may lead to lifestyle-related diseases. For example, when cholesterol in the blood increases, arteriosclerosis progresses and is likely to cause ischemic heart diseases such as angina pectoris and myocardial infarction, and strokes such as cerebral hemorrhage and cerebral infarction.

  Patent Document 1 below discloses a cholesterol-lowering composition containing tea flavins derived from tea as active ingredients. In addition, although this literature describes that thealvidin derived from tea is believed to be useful in the treatment of hyperlipidemia and / or hypercholesterolemia, the effectiveness of the thealvidin is described. There are no test examples to show.

JP 2004-155784 A

As a cholesterol reducing agent, a highly safe thing is desirable.
The present inventors have found that an extract of mixed fermented tea leaves mixed with tea leaves and loquat leaves has the effect of reducing cholesterol, and as a result of intensive research focusing on it, as a result of reducing cholesterol, Since an effective component has been found, a patent application is filed.

  The present invention provides a cholesterol-reducing agent containing as an active ingredient at least one selected from the group consisting of theacinensin and a catechin oxidation polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200.

  According to the present invention, a highly safe cholesterol-reducing agent can be obtained.

It is a figure for demonstrating the component fractionation method of the mixed fermented tea leaves which concern on this invention. It is the chromatogram by HPLC of the fraction obtained by the manufacture example which concerns on this invention. It is a structural formula of the active ingredient which concerns on this invention. It is a ¹³ C-NMR spectrum of an active ingredient and a comparative ingredient concerning the present invention. 3 is an estimated partial structural formula of an active ingredient according to the present invention.

In the present invention, (1) theacinensin used as an active ingredient and (2) a catechin oxidation polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200 are both tea leaves and loquat leaves. Obtained from mixed fermented tea leaves produced as a raw material.
As described in (Example) below, the above (2) catechin oxidation polymer is oxidative of four catechins (epigallocatechin, epicatechin, epigallocatechin gallate, epicatechin gallate) contained in tea leaves. The molecular weight is estimated to be a number average molecular weight (Mn) of 5,970 and a weight average molecular weight (Mw) of 13,200. Generally, black tea produced by fermenting only tea leaves also contains a catechin oxidized polymer.

[Production method of mixed fermented tea leaves]
Mixed fermented tea leaves can be produced by the following method.
The tea leaves used as the raw material are so-called camellia evergreen shrub Camellia sinensis L. Leaves. As the tea leaves, in addition to the first tea, second tea, third tea, autumn / winter tea, banban tea, etc. can be used, and cheap tea leaves after the second tea containing a relatively large amount of polyphenols are preferred. The price of these late banchas is currently sluggish and a considerable amount is discarded, but this can be used effectively.

  The loquat leaves used as a raw material are leaves of the family Rosaceae and the plant name “Biwa”, and can be used without particular limitation.

  In order to produce mixed fermented tea leaves, first, loquat leaves and tea leaves are prepared. As pretreatment, it is preferable to dry loquat leaves and tea leaves as necessary, and to keep the water content at about 50 to 60% by mass. Moreover, it is preferable to cut | disconnect to an appropriate dimension, for example, a magnitude | size about 1-10 mm square.

The tea leaves are then dried, the water content is reduced and wilted. In this process, for example, using a roughing machine, a pot or plate-like appliance heated directly or with electricity, stirring the tea leaves and applying heated air at a temperature of 40 to 150 ° C. to the tea leaves, sealing A method in which tea leaves are put into a stirring container, the air in the container is sucked and the inside is decompressed and stirred and dried, and a method in which air is blown from below the tea leaves sprayed on the net using a wilt tank Etc. are used.
If the moisture content of the raw tea leaves is reduced to 45 to 65% by mass, preferably about 50 to 60% by this wilting, it will be difficult to ooze water from the tea leaves in the next twisting step. Prevents the loss of ingredients. It is also preferable in that the subsequent drying step can be shortened.

Next, the raw tea leaves that have undergone the wilting process are massaged while being pressed (twisted), and loquat leaves are added at the time of this twisting, and both are twisted together. Loquat leaves may be added simultaneously with the start of tea leaf twisting, or after only tea leaf twisting for a certain period of time, loquat leaves may be added and further twisted. It is preferable to add loquat leaves after 0 to 40% of the total twisting time has elapsed since the start of twisting. It is more preferable to add loquat leaves from the beginning of the twisting process.
This twisting destroys the tissue of tea leaves and loquat leaves, and oxidative enzymes such as polyphenol oxidase contained in tea leaves oxidize and polymerize polyphenols contained in tea leaves and loquat leaves, producing an oxidized polymer. To do.

The amount of loquat leaves added is preferably in the range of 5/95 to 35/65, more preferably 8/92 to 25/75. When the amount of loquat leaf added is within the above range, the active ingredients (1) and (2) can be obtained efficiently, and particularly the (2) catechin oxidized polymer is efficiently produced.
For the twisting, a known method such as a method using a normal twisting machine used for twisting tea leaves can be appropriately employed. The twisting time is preferably 15 to 25 minutes. The temperature of the raw material during twisting is preferably 20 to 40 ° C. If it is less than 20 ° C., fermentation is insufficient, and if it exceeds 40 ° C., the active ingredients (1) and (2) cannot be obtained efficiently.

Next, the fermentation process is performed. That is, in a state where the mixed raw material after twisting is deposited to a thickness of several centimeters, the mixture is left in an environment such as a fermentation chamber at a temperature of 20 to 27 ° C. and a humidity of 30 to 60% RH. “Fermentation” in the tea production process means an oxidation reaction by oxidase in leaves.
The fermentation time is preferably 0 to 4 hours. The time for the twisting process is not included in the fermentation process. In the previous twisting process, fermentation starts simultaneously with the start of the twisting process, so that a fermented mixed fermented tea leaf can be obtained even if a fermentation process is not provided separately from the twisting process, that is, even if the fermentation time is 0 hours.

  Next, when a predetermined fermentation time has elapsed, the raw material is heated to stop the fermentation and dried. For example, raw materials are put into a continuous dryer, hot air having a temperature of 80 to 120 ° C. is blown into the continuous dryer, and the exhaust temperature is controlled to be 50 to 60 ° C. A heating time of about 10 to 30 minutes is sufficient, so that the water content in the raw material is about 5% by mass.

  In this way, mixed fermented tea leaves are obtained. The mixed fermented tea leaves used in the present invention may be crude tea after the heating process, or may be finished tea that has been subjected to finishing processing as necessary, and the crude tea or finished tea is pulverized to an appropriate size and powdered. It may be a shape.

[Fractionation of active ingredients]
Mixed fermented tea leaves are extracted, and active ingredients (1) and (2) are fractionated from the extract. As the extraction solvent, water or an organic solvent is used. A mixture of an organic solvent and water may be used as the extraction solvent. Specific examples of the organic solvent include methanol, ethanol, acetone and the like.
The extraction method and the method for fractionating the active ingredient from the extract are not particularly limited, but the active ingredients (1) and (2) can be efficiently obtained by the method shown in FIG.
The extract of mixed fermented tea leaves in the present invention also contains theaflavin, and theaflavins can be fractionated simultaneously with the fractionation of the active ingredients (1) and (2). As disclosed in Patent Document 1, theaflavin is also an effective component for reducing cholesterol.

First, mixed fermented tea leaves are extracted using water as an extraction solvent, and solid-liquid separation is performed to obtain an extract 1 and a residue 2. The temperature of water is preferably about 10 to 25 ° C. In this process, sugar and caffeine sugar are mainly extracted. A part of polyphenols containing active ingredients (1), (2) and theaflavin is also extracted. The obtained extract 1 is subjected to adsorption chromatography using a Sephadex LH-20 column to allow sugar and caffeine to permeate and adsorb only polyphenols.
On the other hand, the residue 2 is extracted with an organic solvent to obtain an extract 3. In this step, polyphenols contained in the tea leaves (residue 2) after water extraction are extracted. When obtaining the extract 3, it is preferable to remove the organic solvent after the extraction operation and concentrate, and further remove unnecessary solids (residue 4) to obtain the extract 3. The extract 3 thus obtained is passed through a Sephadex LH-20 column that has been treated with the extract 1, and the remaining sugar, caffeine, and flavonol glycoside are washed away using a solvent having a low alcohol concentration, The active ingredient is eluted by increasing the concentration to obtain Fraction 2 containing (1) theacinensin, (2) catechin oxidized polymer, and theaflavin.

Next, the obtained fraction 2 was subjected to gel permeation chromatography using a Sephadex LH-20 column using a 7M urea-acetone mixed solution as a solvent, and fraction 2-1 containing a catechin oxide polymer having a large molecular weight was obtained. Fraction 2-2, which contains theacinensin and theaarabin with relatively low molecular weight.
Acetone is distilled off from the fraction 2-1, which is used as an aqueous solution for gel permeation chromatography using a Diaion HP20SS column. The urea and hydrochloric acid are washed away with water, and the polyphenol is eluted with alcohol. 2) A fraction 3-1 of the catechin oxidized polymer is obtained.
On the other hand, fraction 2-2 was also subjected to adsorption chromatography using a Diaion HP20SS column after distilling off acetone, and after rinsing urea and hydrochloric acid with water, elution with alcohol while increasing the alcohol concentration, Theacinensins and theaflavins are separated, and the desired (1) fraction 3-2 of theacinensin and fraction 3-3 of theaflavin are obtained.

In the extraction and fractionation method shown in FIG. 1, first, mixed fermented tea leaves are extracted with water to obtain an extract 1 containing a large amount of water-soluble components and a low content of pophenols. The sugar and caffeine can be easily separated and removed by passing through a column without concentrating. If the extract contained in the column contains a high concentration of sugar, the gel tends to shrink and the load on the column increases. However, the above method can prevent such inconvenience. Moreover, the trouble of concentrating the extract can be saved.
Further, by applying gel permeation chromatography using Sephadex LH-20 with 7M urea-acetone mixture as a solvent to fraction 2 fraction, (2) catechin oxidized polymer having a large molecular weight in one step And a fraction 2-1 that is a fraction containing a relatively small molecular weight (1) theacinensin and theaarabin.
Furthermore, by using Diaion HP20SS column chromatography at the stage of removing urea from fraction 2-2, (1) theasinensins and theaflavins are separated and eluted, and the target active ingredient can be obtained very efficiently. .

[Cholesterol reducing agent]
The fractions each containing (1) theacinensin and (2) catechin oxidized polymer thus obtained can be used as they are as the cholesterol reducing agent of the present invention (hereinafter sometimes referred to as the agent of the present invention). it can. Those obtained by appropriately performing post-treatment such as solvent removal, concentration, and drying on the fraction may be used as an active ingredient of the agent of the present invention.
The agent of the present invention contains one or more selected from the group consisting of (1) theacinensin and (2) a catechin oxidized polymer as an active ingredient. Any of these may be used alone, or two or more of these may be used in combination.
In addition to the active ingredients (1) and (2), the agent of the present invention includes excipients, binders, disintegrants, lubricants, preservatives, stabilizers, preservatives, flavoring agents, diluents, You may contain 1 type, or 2 or more types of additives accept | permitted on formulation, such as a flavoring agent.
Furthermore, you may contain the well-known component which has a cholesterol reduction effect | action and confirmed safety | security, such as theaflavin.

The agent of the present invention can be administered orally to obtain an effect of reducing cholesterol concentration in blood and an effect of reducing cholesterol concentration in liver. The administration method is not particularly limited, but it is preferable to administer continuously over a period of 2 weeks or more.
As for the effective dose of the agent of the present invention, the daily dose for an adult is preferably 10 to 5000 mg, more preferably 50 to 2000 mg, more preferably 50 to 700 mg as the total amount of (1) theaflavin and (2) catechin oxidized polymer. Is more preferable.
In addition to the above active ingredients (1) and (2), when a known ingredient having a cholesterol reducing action such as theaflavin is administered simultaneously, the total amount of these ingredients is preferably within the above range.
The dosage form of the agent of the present invention is not particularly limited, but is preferably an internal dosage form such as a tablet, granule, capsule, liquid medicine, drink or the like. Such formulation can be carried out according to a conventional method used for the production of a medicine.

In the following, “%” is “% by mass” unless otherwise specified.
The "tea leaves" used as raw materials in the following are all the third tea leaves of Yabukita cultivated at the Nagasaki Prefectural Agricultural and Forestry Experiment Station Higashisonobe Tea Leaf Branch.
[Reference Example 1: Production of mixed fermented tea leaves]
The loquat leaves were put into the tea leaves and swallowed with a twister. The blending ratio of tea leaves and loquat leaves was a tea leaf: lowa dry tea mass ratio of 9: 2. The squeezing time was 20 minutes, and the temperature of the raw material during twisting was 33 ° C. After this, it was immediately transferred into a hot air drier and heated at 100 ° C. for 30 minutes to stop fermentation and dry. Thus, a mixed fermented tea leaf having a water content of 5% by mass was obtained.

<Production Example 1>
(Extraction and fractionation)
The active ingredient was extracted and fractionated by the procedure shown in FIG.
First, 1930 g of mixed fermented tea leaves obtained in Reference Example 1 were immersed in 30 L of water (15 ° C.), extracted at room temperature for 2 days, and then suction filtered. The obtained filtrate (Extract 1) was poured into a Sephadex LH-20 column (Pharmacia Fine Chemicals, gel diameter: 10 cm, length: 35 cm) substituted with water to adsorb polyphenol.
On the other hand, the tea leaves after water extraction obtained as residue 2 are 30 L of 50% acetone aqueous solution (acetone: water volume ratio = 1: 1), and the extraction at room temperature is repeated twice for 2 days. The liquids were combined and acetone was distilled off with a rotary evaporator. Methanol was added to the resulting solution containing the precipitate to a concentration of 20% by volume and stirred, and chlorophyll and the like remaining undissolved were removed by filtration. The obtained filtrate (extract 3) was continuously poured into the Sephadex LH-20 column through which the extract 1 was introduced.
Next, 2 L of 40% methanol (methanol: water volume ratio = 4: 6, the same applies hereinafter) was allowed to flow through the column, and sugars, caffeine and flavonol glycosides were allowed to flow out. Further, 2 L of 60% methanol, 2 L of 80% methanol, 4 L of 100% methanol, 2 L of methanol-acetone-water mixture (methanol: acetone: water volume ratio = 8: 1: 1), and acetone water 6 L of the mixture (acetone: water volume ratio = 6: 2) was flowed in this order to elute the components. The eluate was divided into glass containers of 250 ml each, and silica gel thin layer chromatography containing a fluorescent agent for each (developing solvent was a mixture of toluene: ethyl formate: formic acid volume ratio = 1: 7: 1, detection was ultraviolet absorption, and Fractionation was confirmed by confirming the components with iron (III) chloride spray), and the mixture was concentrated to dryness with a rotary evaporator.
Thus, a fraction 1 (52.3 g) mainly containing catechins and a fraction 2 (74.6 g) containing theacinensin, theaflavin, and a catechin oxidized polymer were obtained.

Fraction 2 was dissolved in 7M urea-acetone mixture (volume ratio of urea: acetone = 2: 3, adjusted to pH 2 with hydrochloric acid) and replaced with the same solvent, Sephadex LH-20 column (gel diameter 10 cm, length 35 cm) And fractionated into a fraction 2-1 containing a catechin oxidized polymer and a fraction 2-2 containing theacinensin and theaflavin.
Fraction 2-1 distills acetone to form an aqueous solution, which is poured into a Diaion HP20SS column (Mitsubishi Chemical Co., Ltd., gel diameter: 5 cm, length: 30 cm). Urea and hydrochloric acid are washed away with water, and polyphenol is eluted with methanol Thus, fraction 3-1 (21.4 g) of the catechin oxidized polymer was obtained.
Fraction 2-2, after distilling acetone off, was poured into a Diaion HP20SS column (gel diameter 5 cm, length 30 cm), urea and hydrochloric acid were washed away with water, 0.5 L of 10% methanol, 0 of 20% methanol. Elution with 0.5 L, 0.5 L of 30% methanol, 0.5 L of 40% methanol, 0.5 L of 60% methanol, 0.5 L of 80% methanol, and fraction 3-2 (8.5 g) of theacinensin, The fraction (7.4g, not shown) of the other polyphenol mixture and the fraction 3-3 (30.1g) which has theaflavins as a main component were obtained.

(Identification)
A chromatogram of the obtained fraction by HPLC (high performance liquid chromatography) is shown in FIG. 2A is a chromatogram for the catechin oxidized polymer fraction 3-1, FIG. 2B is the theacinensin fraction 3-2, and FIG. 2C is the theaflavin fraction 3-3.
The HPLC analysis conditions for each sample are as follows.
[Analysis of Catechin Oxidation Polymer and Theacinensin]
Column: Cosmosil 5C ₁₈ AR II (manufactured by Nacalai Tesque, 4.6 × 250 mm),
Column temperature: 35 ° C.
Mobile phase: A; 50 mM phosphoric acid, B; CH ₃ CN, B 4% to 30% (39 minutes), 30% to 75% (15 minutes),
Flow rate: 0.8 ml / min.
[Analysis of theaflavins]
Column: Cosmosil 5C ₁₈ PAQ (manufactured by Nacalai Tesque, 4.6 × 250 mm),
Column temperature: 35 ° C.
Mobile phase: A; 50 mM phosphoric acid, B; CH ₃ CN, B 10% to 25% (5 minutes), 25% to 80% (40 minutes),
Flow rate: 0.8 ml / min.

Theasinensins and theaflavins were identified by comparing the standards with HPLC chromatographs.
As shown in FIG. 2, the main component of the fraction 3-2 is theasinensin A, and the main component of the fraction 3-3 is theaflavins.
The structural formulas of theacinensin A and theaflavins are shown in FIG. Among the theaflavins, TF is a compound in which R ₁ and R ₂ in the structural formula are hydrogen atoms, TF3G is a compound in which R ₁ is a galloyl group and R ₂ is a hydrogen atom, and TF3′G is a compound in which R ₁ is R _1. A hydrogen atom in which R ₂ is a galloyl group and TFdiG are those in which R ₁ and R ₂ are galloyl groups.

(Measurement of molecular weight)
The catechin oxidized polymer obtained above was dissolved in dimethylformamide and analyzed by high performance liquid chromatography for gel filtration. The analysis conditions were as follows.
Column: TSK-gel-α 3000 column, length 300 mm × diameter 7.8 mm (manufactured by Tosoh Corporation),
Flow rate: 0.5 ml / min
Solvent: dimethylformamide containing 10 mM lithium chloride,
Temperature: 40 ° C
Detection: UV absorption at 254 nm.
The molecular weight was estimated from the retention time of the peak top. As molecular weight standard products, polystyrene standard products (molecular weights 4,000, 25,000, 50,000, and 170,000) and toluene (molecular weight 92) were used. As a result, the number average molecular weight (Mn) of the obtained catechin oxidized polymer was 5,970, and the weight average molecular weight (Mw) was 13,200.

<Comparative Production Example 1>
In Production Example 1, the molecular weight was measured in the same manner for the fraction 3-1, which was obtained by carrying out the same treatment except that a commercial black tea was used instead of the mixed fermented tea leaf, and the number average molecular weight (Mn) was It was 2,062 and the weight average molecular weight (Mw) was 10,413.

<Measurement Example 1>
The catechin oxidation polymer obtained in Production Example 1 was dissolved in heavy acetone containing 5% heavy water, and a ¹³ C-NMR spectrum was measured. The result is shown in FIG.
For comparison, ¹³ C-NMR spectra were measured in the same manner for procyanidins (epicatechin polymerized epicatechin) obtained from black tea polymer polyphenols and fresh loquat leaves. The result is shown in FIG.
(A) of FIG. 4 is a spectrum about the catechin oxidation polymer obtained by manufacture example 1, (B) is a high molecular weight polyphenol of black tea, (C) is a spectrum about procyanidins of loquat leaves.
From the result of this figure, it can be seen that the catechin oxidized polymer obtained in Production Example 1 has both the characteristic signal of black tea polymer polyphenol and the characteristic signal of loquat procyanidin. From this, procyanidins contained in loquat leaves may coexist or may be copolymerized with tea catechins.
In addition to the signal common to the catechin skeleton (indicated by F in the figure), the ¹³ C-NMR spectrum of FIG. 4A shows the signal of pyrogallol-type catechin characteristic of epigallocatechin (indicated by pyr in the figure). And a signal derived from a catechol-type catechin characteristic of epicatechin (indicated by “cat” in the figure), and a signal derived from a galloyl group ester-linked thereto (indicated by “G” in the figure). From this, the catechin oxidation polymer obtained in Production Example 1 is formed by oxidatively binding four kinds of catechins (epigallocatechin, epicatechin, epigallocatechin gallate, epicatechin gallate) contained in tea leaves. It can be seen that this is a polymer compound.
The estimated partial structural formula of the catechin oxidized polymer obtained in Production Example 1 is shown in FIG. The deduced partial structural formula is the chemical structure of a substance obtained by enzymatic oxidation of catechin (Li, Y., et. Al., Pytochemistry, 2007, 68, 1081; Kusano, R., et. Al., Chem. Pharm. Bull., 2007, 56, 1768) and the structure of loquat leaf proanthocyanidins.

<Test Example 1: Effect on serum total cholesterol and liver total cholesterol>
Using the theacinensin, theaflavin, and the catechin oxidized polymer obtained in Production Example 1, the effects on the serum total cholesterol concentration and the liver total cholesterol concentration when rats were fed a diet containing these components were examined.
A 4-week-old Sprague-Dawley (normal rat) was used as an experimental animal, and was raised in an animal breeding room with a light cycle of room temperature 22 ± 1 ° C., humidity 55 ± 5%, and 8:00:00 to 20:00 lighting. Up to 5 weeks of age, a commercially available MF solid feed (produced by Oriental Yeast Co., Ltd.) was given for pre-breeding, and then feeding of the test meal was started. That is, 7 mice per group were grouped into a total of 5 groups (I) to (V) so that the average weight would be the same at the age of 5 weeks, and the following test meals were allowed to eat freely for 4 weeks. It was.
As the test meal, a purified meal based on AIN-76 was used as a control meal. The composition (unit: g / kg) is: casein 200, corn oil 100, mineral mixture (AIN-76-MX) 35, vitamin mixture (AIN-76-VX) 10, cellulose 50, choline bitartrate 2, DL- Methionine 3, corn starch 150 and sucrose 450.
Group (I): A control diet was directly taken as a test diet.
Group (II): A test meal in which 0.2% of theacinensin was added to the control meal and sucrose was reduced by the added amount.
Group (III): A test meal in which 0.2% theaflavin was added to the control meal and sucrose was reduced by the added amount.
Group (IV): A test meal in which 0.5% catechin oxidized polymer was added to the control meal and sucrose was reduced by the added amount.
Group (V): A test meal in which both 0.2% theacinensin and 0.2% theaflavin were added to the control meal, and sucrose was reduced by the added amount.
In both groups, food intake and body weight were measured every other day during the breeding period. Serum total cholesterol concentration and liver total cholesterol concentration were measured 4 weeks after the start of intake of the test meal. The measurement results are shown in Table 1.

Serum total cholesterol concentration is cholesterol esterase 3,5-dimethoxy-N-ethyl-N- (2-hydroxyl-3-sulfopropyl) -aniline sodium-cholesterol E-test Wako by DAOS method (Wako Pure Chemical Industries, Osaka, Japan) ).
The total liver cholesterol concentration was determined by first extracting the total liver lipids using the Folch method [Folch J, Lees M, Sloane-stanley GH .: A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem, 226: 497 -506 (1957)], and after extraction, the serum total cholesterol concentration was measured by the same method.

From the results shown in Table 1, the serum total cholesterol concentrations were as follows: (II) group fed with 0.2% theacinensin diet, (III) group fed with 0.2% theaflavin diet, 0.5% catechin oxidation weight The rats in the (IV) group that received the combined diet and the rats in the (V) group that received a diet containing both the 0.2% theacinecin diet and the 0.2% theaflavin diet were larger than the rats in the (I) group. Declined.
The total liver cholesterol levels were lower in all groups compared to group (I), especially in group (II) and 0.2% catechin oxidized polymer diet in which 0.2% theasinensin diet was consumed. The level was significantly reduced in the rats in the (IV) group ingested.
From these facts, it was confirmed that the theasinensin and catechin oxidized polymer according to the present invention have the effect of lowering the serum total cholesterol concentration and the liver total cholesterol concentration.
It was also confirmed that theaflavin has the effect of reducing serum total cholesterol concentration and liver total cholesterol concentration.
Since these active ingredients are ingredients contained in the mixed fermented tea leaves, they are highly safe.

Claims (1)

A cholesterol reducing agent comprising a catechin oxidized polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200.

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