JP5703932B2 - Novel phenolic dimer compounds - Google Patents

Description

  The present invention relates to a novel phenolic dimer compound having anticancer activity and a method for producing the same, and an anticancer agent, food, medicine or quasi-drug containing the novel phenolic dimer compound.

  Both p-coumaric acid and ferulic acid are one of the secondary metabolites of plants. For example, they are precursors of lignin and lignan, which are the main components of trees, and are relatively abundant in nature. As p-coumaric acid, it is known that it is also contained in fruits, peels and propolis of many fruits including plum. On the other hand, ferulic acid is abundant in the skin layer of rice bran and potato. These are all ingredients that have dietary experience and are highly safe for humans.

  Regarding p-coumaric acid, there is a prior art related to its physiological function. For example, p-coumaric acid, anti-Helicobacter pylori agent containing cinnamic acid as an active ingredient (Patent Document 1), skin improving agent containing ferulic acid and / or p-coumaric acid as an active ingredient (Patent Document 2), Examples thereof include an angiogenesis inhibitor (Patent Document 3) containing cinnamic acid contained in a propolis extract including coumaric acid as an active ingredient. Ferulic acid also has prior art related to its physiological function. For example, a cell differentiation promoting agent containing ferulic acid as an active ingredient (Patent Document 4), an external preparation for skin whitening containing ferulic acid as an active ingredient (Patent Document 5), an antioxidant containing ferulic acid as an active ingredient (Patent Document) 6), a coloring aid for fish eggs composed of ferulic acid and nicotinic acid amide (Patent Document 7), an antibacterial agent containing ferulic acid as an active ingredient (Patent Document 8), and an Alzheimer's disease preventive effect of ferulic acid (Non-Patent Document 1) )It has been known.

There is also prior art related to p-coumaric acid derivatives. For example, an antibacterial agent containing a lignin chemically synthesized from coumaric acid (Patent Document 9), an adiponectin production enhancer containing a caffeic acid amide derivative or an ester derivative as an active ingredient (Patent Document 10), p-coumaru A method for synthesizing a benzofurancarboxamide derivative that is an antibacterial agent using an acid dimer as a raw material (Patent Document 11) can be mentioned.
Moreover, since many p-coumaric acid derivatives are also contained in plants, as a fruit polyphenol of an immature fruit of apple, pear or peach, an antioxidant containing a p-coumaric acid derivative, a blood pressure lowering agent, An antimutagenic agent, an allergy inhibitor, an anticaries agent and a deodorant (Patent Document 12) can be mentioned. In addition, as prior arts related to ferulic acid derivatives, for example, an ultraviolet absorber having a ferulic acid ester derivative as an active ingredient (Patent Document 13), an external skin drug having a ferulic acid ester of phytosterols as an active ingredient (Patent Document) 14) is known.

  Moreover, since many p-coumaric acid, ferulic acid, and derivatives thereof show excellent usefulness, techniques for efficiently producing these as raw materials and lead compounds have also been proposed. An example of a method for producing p-coumaric acid is a method for producing p-hydroxycinnamic acid (p-coumaric acid) or the like by a microorganism using a recombinant (Patent Document 15). Examples of the production method of ferulic acid include production by condensation reaction of vanillin and malonic acid (Non-patent Document 2), production method from rice bran (Patent Document 16), and production method using eugenol as a raw material (patent) Document 17), an enzyme production method from coniferyl aldehyde (Patent Document 18) and the like are known.

  As described above, a number of p-coumaric acid, ferulic acid and their derivatives, and methods for producing these compounds as raw materials have been proposed, but p-coumaric acid, ferulic acid and their derivatives were used. There is a demand for further development of new materials and further expansion of usage of materials.

JP-A-11-106335 Japanese Patent No. 3309961 JP 2007-223948 A JP-A-5-310526 JP-A-6-256137 JP-A-9-221667 JP 2000-325049 A JP 2000-247900 A Japanese Patent No. 4395623 JP 2007-262050 A JP 2008-189554 A Japanese Patent Laid-Open No. 2002-47196 JP 2003-128632 A JP-A-8-81352 JP-T-2005-522180 Japanese Patent Publication No. 7-78032 Japanese Patent Laid-Open No. 9-154591 Japanese Patent Laid-Open No. 10-155596

British Journal of Pharmacology, 133, 89-96 (2001) Journal of the American Chemical Society, 74, 5346-5348 (1952).

  In view of the above situation, the present inventors have surprisingly investigated p-coumaric acid and ferulic acid-related compounds having novel physiological activities, and conducted extensive studies to establish a production method thereof. -To find a compound having anticancer activity that is not found in p-coumaric acid and ferulic acid, which are raw materials, only by heating coumaric acid and ferulic acid under alkaline conditions, and to complete the present invention. It came.

Accordingly, an object of the present invention is to provide a novel phenolic dimer compound having excellent anticancer activity, and to provide a method for producing it efficiently and safely.
In addition, the present invention provides an anticancer agent containing the novel phenolic dimer compound as an active ingredient, and further a food, pharmaceutical or quasi-drug containing the novel phenolic dimer compound represented by the formula (1). The purpose is to provide.

The gist of the present invention is as follows:
[1] The following formula (1):

A novel phenolic dimer compound represented by: or a pharmaceutically acceptable salt thereof,
[2] An anticancer agent comprising at least one compound selected from the group consisting of the novel phenolic dimer compound according to [1] and a pharmaceutically acceptable salt thereof,
[3] above [1] novel phenolic dimer compound according and foods, characterized by containing one or more compounds selected from the group that consisting of pharmaceutically acceptable salts,
[4] A pharmaceutical or quasi-drug comprising one or more compounds selected from the group consisting of the novel phenolic dimer compound of [1] and a pharmaceutically acceptable salt thereof ,
[ 5 ] A novel phenolic compound represented by the above formula (1), characterized in that p-coumaric acid and ferulic acid are heat-treated at 90 ° C. or higher under alkaline conditions to produce the target compound. Method for producing monomeric compound,
About.

According to the present invention, it is possible to provide a novel phenolic dimer compound excellent in physiological activity as described above and a method for producing the same. Moreover, since the compound which has the anticancer activity which is not recognized by p-coumaric acid and ferulic acid of a raw material by this invention can be manufactured, the outstanding anticancer agent can be provided.
Since the novel phenolic dimer compound of the present invention is excellent in safety in addition to being excellent in physiological activity as described above, it can be incorporated into foods, pharmaceuticals, or quasi drugs.

FIG. 1 shows the results of HPLC analysis performed in Example 1. From the top, after reaction of only p-coumaric acid, after reaction of ferulic acid only, and after reaction of a mixed solution of p-coumaric acid and ferulic acid, “A” is obtained using p-coumaric acid and ferulic acid as raw materials. The peak of the novel phenolic dimer compound thus produced is shown.

  Hereinafter, the present invention will be described in detail.

  The novel phenolic dimer compound of the present invention has the formula (1):

The structural formula is represented by:

  In the present invention, the novel phenolic dimer compound represented by the formula (1) may be a pharmaceutically acceptable salt. Examples of the pharmaceutically acceptable salt include alkali metal salts such as lithium salt, sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt, calcium salt and barium salt; aluminum salt; aluminum hydroxide salt and the like Metal hydroxide salts of; amine salts such as alkylamine salts, dialkylamine salts, trialkylamine salts, alkylenediamine salts, cycloalkylamine salts, arylamine salts, aralkylamine salts, heterocyclic amine salts; α-amino acid salts And amino acid salts such as ω-amino acid salts; peptide salts or primary, secondary, tertiary or quaternary amine salts derived therefrom. These pharmacologically acceptable salts can be used alone or in admixture of two or more.

  The novel phenolic dimer compound of the present invention can be produced by heat-treating p-coumaric acid and ferulic acid under alkaline conditions.

  The novel phenolic dimer compound of the present invention can be chemically synthesized using raw materials other than p-coumaric acid and ferulic acid, but in this case, the reaction process is complicated and harmful reagents and processes. Need. Moreover, since it is necessary to thoroughly refine from the viewpoint of safety of removing impurities, it is an industrially unsuitable method. On the other hand, the method for producing the novel phenolic dimer compound of the present invention includes a step of heat-treating p-coumaric acid and ferulic acid, which can be obtained at low cost, under alkaline conditions, and is harmful. It is an efficient and safe manufacturing method that does not require reagents or dangerous processes.

  P-Coumaric acid and ferulic acid are required as precursors of the novel phenolic dimer compound of the present invention. These may be of natural origin or chemically synthesized chemical products with high purity. In the case of using a naturally occurring one, it is not necessary to be completely purified. If the desired reaction proceeds and finally a novel phenolic dimer compound is obtained, p-coumaric acid, ferulic acid In addition to the above, a mixture containing other components may be used. However, from the viewpoint of the recovered amount, a mixture containing 5% by weight or more of p-coumaric acid and ferulic acid is desirable as a raw material. Examples of such raw materials include various fruits and juices, concentrated fruit juices or extracts of frequently peeled skin, propolis or extracts thereof, ferulic acid, rice bran or ferulic acid as a food additive, or prior art Examples include a culture solution containing p-coumaric acid or ferulic acid obtained by microbial fermentation, a solution containing p-coumaric acid or ferulic acid after enzymatic reaction, and the like.

  A pure product of p-coumaric acid and ferulic acid, or a mixture containing p-coumaric acid and ferulic acid is dissolved in a suitable solvent. At this time, if the solvent is only water, the solubility of p-coumaric acid and ferulic acid is remarkably low. There is no restriction | limiting in particular in the compounding ratio of water and an organic solvent, and the kind of organic solvent, p-coumaric acid and ferulic acid should just fully melt | dissolve. Desirably, it is desirable from the viewpoint of safety and cost to use only methanol or ethanol, or a mixture of water and methanol, water and ethanol, or the like. As the solvent, ethanol or water-containing ethanol is desirable from the viewpoint of safety and legal regulations when a reaction solution obtained without sufficiently applying final purification is used for food.

The solution containing the mixture of p-coumaric acid and ferulic acid obtained above (hereinafter referred to as p-coumaric acid and ferulic acid mixed solution) is adjusted to be alkaline. For example, after preparing a mixed solution of p-coumaric acid and ferulic acid, the pH may be adjusted by adding a pH adjusting agent, or the pH of the solvent is adjusted in advance when preparing the mixed solution of p-coumaric acid and ferulic acid. You can keep it. When the pH is finally 7.1 or more, the formation reaction proceeds. However, when the pH exceeds 13.0, the formation reaction of the other compound and the decomposition of the target compound occur at the same time as the formation reaction. The final recovered amount of the polymerizable compound is reduced. Therefore, in the production method of the present invention, the pH of the mixed solution of p-coumaric acid and ferulic acid at the start of the production reaction is preferably alkaline, and particularly preferably adjusted to 7.0 to 13.0.
Moreover, in the manufacturing method of this invention, since the production | generation reaction can be advanced efficiently by adjusting the pH of the p-coumaric acid and ferulic acid mixed solution in a production | generation reaction to 7.0-13.0, it is preferable.

  Moreover, there is no restriction | limiting in the density | concentration of p-coumaric acid and ferulic acid of p-coumaric acid and ferulic acid mixed solution. Since the higher the concentration, the smaller the amount of solvent used, and the like, the concentration is preferably near the concentration that saturates with respect to each solvent. Further, p-coumaric acid or ferulic acid may be contained at a concentration higher than the saturation level. In this case, p-coumaric acid and ferulic acid may not be completely dissolved in the solvent before the production reaction. Undissolved p-coumaric acid and ferulic acid are gradually dissolved as the production reaction proceeds.

Although there is no restriction | limiting in particular as a pH adjuster which can be used in order to adjust p-coumaric acid and ferulic acid mixed solution to alkalinity, From a safety | security, efficiency, and a cost surface, sodium hydroxide, potassium hydroxide, hydrogen carbonate Sodium or the like is desirable. In particular, sodium hydrogencarbonate is more desirable because the pH does not exceed 13 even when added in excess. Moreover, when suppressing the pH change of the p-coumaric acid and ferulic acid mixed solution at the time of a production | generation reaction as much as possible, you may use a buffer solution.

  In the present invention, the p-coumaric acid and ferulic acid mixed solution is heated under alkaline conditions. In order to efficiently advance the desired production reaction, the heating temperature needs to be 90 ° C. or higher. Considering the boiling point of the solvent, pressure heating is desirable. The mixed solution is heated in an open container at a high temperature, the mixed solution is heated in a sealed container, heated under pressure using a retort device or an autoclave, etc. It is necessary to reach above ℃. From the viewpoint of recovery efficiency, it is more preferable that the solution temperature be uniformly 90 to 150 ° C. The heating time is not limited as in the case of the heating temperature, and may be a time condition in which the target reaction efficiently proceeds. In particular, the heating time depends on the heating temperature, and it is desirable to set the heating time according to the heating temperature. For example, when heating near 130 ° C., a heating time of 5 minutes to 300 minutes is desirable. Further, the heating reaction may be performed once, or may be repeated in a plurality of times, and may be judged from the viewpoint of efficiency.

  Although the detailed reaction mechanism is not clear by heating the p-coumaric acid and ferulic acid mixed solution, p-coumaric acid and ferulic acid react with each other, and the novel phenolic property represented by the formula (1) A mixture containing the dimer compound is obtained. When only a safe raw material is used, it can be used even in the state of a mixture containing a novel phenolic dimer compound. For example, when p-coumaric acid and ferulic acid derived from nature are dissolved in a water-containing ethanol solvent, sodium bicarbonate is added and heated to react, the reaction mixture containing a novel phenolic dimer compound is used as a food. It can be used as one of the raw materials.

  In addition, completion | finish of the production | generation reaction of the novel phenolic dimer compound represented by the said Formula (1) by the said heat processing is the novel phenolic 2 amount represented by the said Formula (1) by the component analysis by HPLC, for example What is necessary is just to confirm and confirm the production amount of a body compound.

  When improvement in flavor and further enhancement of functionality are desired, the novel phenolic dimer compound of the present invention can be concentrated from the mixture after the reaction to increase the concentration or purified to obtain a pure product. Concentration and purification can be performed by a known method. For example, it can be extracted and concentrated by a solvent extraction method such as chloroform, ethyl acetate, ethanol or methanol, a supercritical extraction method using carbon dioxide gas, or the like. It is also possible to perform concentration and purification using column chromatography. A membrane treatment method such as a recrystallization method or an ultrafiltration membrane can also be applied. Finally, when the solvent is removed by drying under reduced pressure or freeze drying, a pure product of the powdered novel phenolic dimer compound of the present invention can be obtained.

  The novel phenolic dimer compound of the present invention has excellent anticancer activity as described later.

  In addition, the novel phenolic dimer compound of the present invention is used as food, pharmaceuticals, or quasi drugs in various forms such as liquid, paste, gel, solid, etc. for the purpose of anticancer effect. Can do.

  For example, in the case of food, such as water, alcohol, starch, protein, fiber, sugar, lipid, vitamin, mineral, flavoring, coloring, sweetener, seasoning, stabilizer, preservative, etc. Use the novel phenolic dimer compound of the present invention in combination with raw materials or ingredients normally blended in foods, and in the case of pharmaceuticals, in combination with carriers, excipients, diluents, stabilizers, etc. Can do. In particular, considering the physiologically active field possessed by the novel phenolic dimer compound of the present invention, it is preferably used for promoting health maintenance such as cancer prevention and cancer treatment.

  The further effect and efficacy of the novel phenolic dimer compound of the present invention can be used within a range that can be inferred from the obtained physiological activity data.

  When the novel phenolic dimer compound of the present invention is used for pharmaceutical purposes, for example, the intake amount of the novel phenolic dimer compound of the present invention can provide a desired improvement effect, therapeutic effect or preventive effect. It is not particularly limited as long as it is an amount, and it is usually appropriately selected according to the form, age, sex, constitution and other conditions of the patient, the type and degree of disease, and the like. The intake is preferably about 0.1 mg to 1,000 mg per day, which can be divided into 1 to 4 times per day.

  The novel phenolic dimer compound of the present invention can be used in foods such as functional foods, health foods and health-oriented foods. The form of the food may be any form such as a beverage, alcoholic beverage, jelly, confectionery, etc. For example, among confectionery, hard candy, soft candy, gummy that is excellent in storage and carrying due to its capacity, etc. Examples include candy and tablets, but there is no particular limitation.

  In addition, when the novel phenolic dimer compound of the present invention is orally administered or ingested as a pharmaceutical, quasi-drug or food, based on conventional methods, tablets, pills, capsules, fine granules, It may be a granule or the like. If necessary, the granules of capsules containing tablets, pills, granules, granules can be sugar-coated with sugars such as sucrose, sugar alcohols such as maltitol, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, etc. It can also be coated. Alternatively, it may be covered with a film of gastric or enteric material. Moreover, in order to improve the solubility of a formulation, a well-known solubilization process can also be performed. Based on a conventional method, it may be used in an injection or a drip.

  Since the above-mentioned pharmaceutical, quasi-drug, or food is excellent in safety, not only for humans, for example, non-human animals such as rats, mice, guinea pigs, rabbits, sheep, pigs It may be added to therapeutic agents, preventive agents or feeds for mammals such as cattle, horses, cats, dogs, monkeys, chimpanzees, birds, amphibians, reptiles, etc.

  EXAMPLES Next, although this invention is demonstrated in detail based on an Example, this invention is not limited only to this Example.

(Example 1: Production of a novel phenolic dimer compound)
1 g each of p-coumaric acid (manufactured by Wako Pure Chemical Industries, Ltd.) and ferulic acid (manufactured by Wako Pure Chemical Industries, Ltd.) were dissolved in 20 mL of ethanol, and a mixed solution (pH 20%) containing 5% aqueous sodium hydrogen carbonate solution was added. = 7.5) was heated in an autoclave (trade name “SANYO LABO AUTOCLAVE”, manufactured by Sanyo Electric Co., Ltd.) at 130 ° C. for 40 minutes. 1 mL of the resulting post-reaction composition was made up to 50 mL with methanol, and 10 μL of this was analyzed by HPLC.
HPLC analysis was performed under the following conditions.
Column: Column for reverse phase “Develosil (registered trademark) C-30-UG-5” (4.6 mm.d. × 250 mm)
Mobile phase: A: H ₂ O (0.1% trifluoroacetic acid (TFA)), B: Acetonitrile (0.1% TFA)
Flow rate: 1 mL / min
Injection: 10 μL
Detection: 254 nm
Gradient (% by volume): 30 minutes from 80% A / 20% B to 20% A / 80% B, 5 minutes from 20% A / 80% B to 100% B, 10 minutes at 100% B (all linear)

  The chromatogram obtained in Example 1 is shown in FIG. From the top, chromatograms of the solution after the reaction of only p-coumaric acid, the solution of the reaction product of ferulic acid only, and the solution after the formation reaction of the mixture of p-coumaric acid and ferulic acid are shown. A peak different from that reacted with p-coumaric acid and ferulic acid alone is observed. Therefore, the compound indicated by the peak of A is considered to be a product derived from both ferulic acid and p-coumaric acid.

(Example 2: Isolation and structure determination of a novel phenolic dimer compound)
The compound contained in the peak shown by A in FIG. 1 in the reaction product obtained in Example 1 was isolated by preparative HPLC. When dried according to a conventional method, 95 mg of a novel compound (hereinafter referred to as UHA8015) in the form of a yellow powder was obtained.

Subsequently, when the molecular weight of UHA8015 was measured by high resolution electron ionization-mass spectrometry, the measured value was 270.3236, and the following molecular formula was obtained from comparison with the theoretical value.
UHA8015
Theoretical value C17H18O3 (M ⁺ ): 270.3230
Molecular formula C ₁₇ H ₁₈ O ₃

  Next, the UHA8015 was subjected to nuclear magnetic resonance (NMR) measurement, and from the analysis of 1H-NMR, 13C-NMR and various two-dimensional NMR data, it was confirmed that UHA8015 had a structure represented by the formula (1). did. From this, it was shown that the novel phenolic dimer compound represented by the formula (1) can be efficiently produced by the method of the present invention.

  In addition, about each NMR measurement value, each site | part of UHA8015 represented by Formula (1) is shown.

1H nuclear magnetic resonance spectrum and 13C nuclear magnetic resonance spectrum are shown in Table 1.
Values are δ and ppm, measured with methanol-d3.

The physicochemical properties of UHA8015 are as follows.
(Properties)
Yellow powder (soluble)
Water: Insoluble methanol: Soluble ethanol: Soluble DMSO: Soluble chloroform: Soluble ethyl acetate: Soluble

(Example 3: Anticancer activity of UHA8015)
Next, in order to see the effect of each compound on cancer cells, the cancer cell proliferation inhibitory action using HL-60 cells (Human proneolytic leukemia cells: human myeloid leukemia cells) was tested.

For the culture of HL-60 cells, a high nutrient medium “RPMI-1640” containing 4 mM glutamine (L-Glutamine, manufactured by Sigma-Aldrich Japan Co., Ltd.) and 10% FBS (Foetal Bovine Serum, manufactured by Biological Industries) ( Sigma Aldrich Japan Co., Ltd.) was used. In the test, a 96-well plate for cell culture (manufactured by Corning Japan Co., Ltd.) was used, and HL-60 cells adjusted to have 5 × 10 ⁵ cells / mL were seeded at 100 μL per well.
Three types of samples, p-coumaric acid, ferulic acid, and UHA8015 which has been purified, were used. For sample preparation, each compound was dissolved in DMSO (dimethyl sulfoxide, Wako Pure Chemical Industries, Ltd.), and the final concentrations in the HL-60 cell culture were 6.3 μM, 12.5 μM, 25 μM, 50 μM, and 100 μM, respectively. The test was started under the culture conditions of 37 ° C. and 5% CO ₂ . A negative control was prepared by adding the same amount of DMSO as a solvent.
The number of viable cells was quantified by the MTT method using “Cell counting kit-8” (manufactured by Dojindo Laboratories). After 24 hours from the start of the test, 10 μL of the cell counting kit-8 solution was added to each well and stirred well. After the light-shielding reaction for 1 hour, the absorbance at a measurement wavelength of 450 nm is measured using a plate reader (“BIO-RAD Model 680” manufactured by Bio-Rad Laboratories), and the cell viability is calculated based on the obtained data. Calculated. The cell viability is a value calculated by setting the number of viable cells in a culture solution to which only DMSO as a solvent is added as 100% and the number of viable cells in each compound concentration as a relative value. From the relationship between the concentration of each compound and the cell viability, a concentration IC ₅₀ (50% inhibitory concentration) that suppresses cell proliferation by 50% was calculated (Table 2). From these results, it was confirmed that UHA8015 has a cancer cell growth-inhibiting ability not found in p-coumaric acid or ferulic acid as raw materials.

(Example 4: Difference in production amount of UHA8015 depending on heating temperature)
p-Coumaric acid 50 mg, ferulic acid 50 mg, ethanol 1 mL, 5% aqueous sodium hydrogen carbonate solution 1 mL added to a mixture (pH = 7.5) in an autoclave at 70 ° C., 90 ° C., 110 ° C., 130 ° C. Heated for 20 minutes under temperature conditions. 1 mL of the post-reaction composition obtained under each temperature condition was diluted to 50 mL with methanol and analyzed by HPLC in the same manner as in Example 1.

  As a result, the formation of UHA8015 could be confirmed under conditions exceeding 90 ° C. The production ratio of UHA8015 from p-coumaric acid and ferulic acid was non-produced at 70 ° C, trace amount at 90 ° C, 1 wt% at 110 ° C, and 4.7 wt% at 130 ° C. That is, heating at 130 ° C. was the most efficient.

(Example 5: Preparation of UHA8015-containing extract)
Propolis (p-coumaric acid-containing raw material) 10 g, ferulic acid (food additive, manufactured by Tsukino Rice Fine Chemical Co., Ltd.) 0.5 g, ethanol 10 mL, 5% aqueous sodium bicarbonate solution 10 mL mixed solution (pH = 7.6) was heated in an autoclave at 130 ° C. for 60 minutes. The obtained reaction solution was heated under reduced pressure to dryness to obtain 12 g of UHA8015-containing extract. In 12 g of the obtained UHA8015-containing extract, 0.05 g of UHA8015 was contained when confirmed by the same method as in Example 1. This work was repeated as necessary.

  Hereinafter, formulation examples in which UHA8015 obtained in Examples 1 and 2 and UHA8015-containing extract obtained in Example 5 (hereinafter referred to as UHA8015-containing extract) are blended are shown as examples.

(Example 6: Food containing UHA8015)
1 g of UHA8015-containing extract is dissolved in 100 mL of ethanol in advance, 500 g of sugar and 400 g of starch syrup are mixed and dissolved in this, 100 g of fresh cream, 20 g of butter, 70 g of condensed milk, and 1.0 g of emulsifier are mixed, and then -550 mmHg in a vacuum kettle. The mixture was depressurized and concentrated at 115 ° C. to obtain a milk hard candy having a moisture value of 3.0% by weight. This milk hard candy is not only easy to eat as a confectionery, but also can be used as a functional food that is expected to prevent cancer by its anticancer action.

(Example 7: Drug containing UHA8015)
UHA8015 obtained by the methods of Examples 1 and 2 was dissolved in ethanol, adsorbed onto microcrystalline cellulose, and then dried under reduced pressure. This was tableted according to a conventional method. The formulation is 10 parts by weight of UHA8015, 23 parts by weight of corn starch, 12 parts by weight of lactose, 8 parts by weight of carboxymethyl cellulose, 32 parts by weight of microcrystalline cellulose, 4 parts by weight of polyvinylpyrrolidone, 3 parts by weight of magnesium stearate, and 8 parts by weight of talc. It is. This tableted product can be effectively used as a medicine for cancer treatment.

(Example 8: Quasi-drug containing UHA8015)
1.2 g of UHA8015 obtained by the method of Examples 1 and 2 was dissolved in 10 mL of ethanol, and 20 g of taurine, 0.12 g of vitamin B1 nitrate, 0.6 g of sodium benzoate, 4 g of citric acid, and 10 g of polyvinylpyrrolidone were all purified water. And made up to 1000 mL. The pH was adjusted to 3.2 using dilute hydrochloric acid. 50 ml of 1000 ml of the obtained solution was filled in a glass bottle and sterilized at 80 ° C. for 30 minutes to complete a quasi-drug drink. In addition to the purpose of nutritional supplementation, this drink is effectively used as a quasi-drug for the purpose of reducing the risk of cancer spread, reducing the risk of developing cancer, and preventing cancer. it can.

Claims (5)

A novel phenolic dimer compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof.

  An anticancer agent comprising at least one compound selected from the group consisting of the novel phenolic dimer compound according to claim 1 and a pharmaceutically acceptable salt thereof. New phenolic dimer compounds and food products, characterized by containing one or more compounds selected from the group that consisting of pharmaceutically acceptable salt thereof according to claim 1. A pharmaceutical or quasi-drug containing one or more compounds selected from the group consisting of the novel phenolic dimer compound according to claim 1 and a pharmaceutically acceptable salt thereof. A novel phenolic dimer compound represented by the following formula (1), characterized in that p-coumaric acid and ferulic acid are heat-treated at 90 ° C. or higher under alkaline conditions to produce the desired compound. Manufacturing method.

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