JP2021107450A - Antitumor method or antitumor material using mixture of fucoidan with moromi vinegar - Google Patents

Abstract

To realize a technique whereby the proliferation rate of tumor cells can be more decreased by administering a mixture comprising less expensive moromi (sake mash) vinegar.SOLUTION: The proliferation rate of tumor cells is decreased by using a material comprising a mixture of marine alga-derived fucoidan and moromi vinegar. In particular, by using a mixture of acetyl fucoidan separated from Cladosiphon okamuranus Tokida with moromi vinegar, the less expensive moromi vinegar can substitute for the acetyl fucoidan and thus an effect of reducing the amount of the expensive acetyl fucoidan to be used can be achieved. The moromi vinegar as described above is used in an amount of 3-95%. The fucoidan as described above is derived from a marine alga such as Nemacystus decipiens, Undaria pinnatifida, Undaria pinnatifida sporophyll, Laminariaceae algae, Sargassum fusiforme, Sargassum horneri (Turner) C. Agardh or a marine alga belonging to the family Sargassaceae.SELECTED DRAWING: Figure 1

Description

The present invention relates to an invention in which fucoidan such as expensive acetyl fucoidan can be reduced and cheap mash vinegar can be substituted by a method or substance of mixing fucoidan and mash vinegar.

As in Patent Document 1, in order to provide a health food beverage containing mozuku extract that is easy to drink and easily absorbed by the body, mozuku is the main component, and vinegar, brown sugar and appropriate drinking water are added to this. At the same time as mixing and stirring and heat-treating, an AC voltage is applied for a certain period of time by an electrostatic induction device, the molecules of the above solution are refined by electrostatic induction, and then sterilized. Is known. When extracting mozuku extract, that is, fucoidan, in addition to the electrostatic induction action by an AC high-voltage electric field using an electrostatic induction reaction device, an electromagnetic AC magnetic field is simultaneously applied to frosted vinegar and mozuku to cause electrons and atoms. Also known are inventions in which fucoidan has a molecular weight that is easily absorbed by the body through action at the molecular level.

Further, as in Patent Document 2, it is produced from cultured Okinawa mozuku as a raw material for the purpose of providing a pharmaceutical composition for oral administration for treating a malignant tumor developed in the digestive tract containing acetylfucoidan as an active ingredient. Acetylfucoidan was dissolved in water and orally administered to reduce the weight and increase the weight of malignant tumors in mice in which colon 26 cells, which are celllines derived from mouse colon cancer, were transplanted into the intestine to develop colon cancer. Was significantly reduced (P = 0.05).

Japanese Unexamined Patent Publication No. 2008-22787 Japanese Patent Application Laid-Open No. 2009-185009

However, as in Patent Document 2, acetylfucoidan is promising as a pharmaceutical composition for oral administration for treating a malignant tumor developed in the gastrointestinal tract. However, since acetylfucoidan is extremely expensive, it is difficult to put it into practical use for economic reasons.
Focusing on such a problem, the technical subject of the present invention has clarified that the growth rate of tumor cells can be further suppressed by mixing and administering inexpensive mash vinegar.

When the present inventor compares a solution to which only acetylfucoidan or moromi vinegar is added and a solution to which a mixed solution of both is added, the antitumor activity of the mixed solution of both is unexpectedly compared with that added alone. It was found that it showed a high rate of decrease. Then, further studies were carried out, and the present invention was completed.

That is, the present invention solves the above problems by providing the invention described below.
(1) A pharmaceutical composition for treating tumors containing fucoidan and moromi vinegar.
(2) A pharmaceutical composition containing fucoidan and mash vinegar that suppresses the growth rate of tumor cells.
(3) The pharmaceutical composition according to (1) or (2), wherein the fucoidan is derived from seaweed of the family Mozuku, Wakame, Mekabu, Kombu, Hijiki, Sargassum horneri and / or Sargassum.
(4) The claim (1) or (2), wherein the mash vinegar is a mash vinegar stock solution and / or a deodorized mash vinegar and / or a mash vinegar powder and / or a deodorized mash vinegar powder. The pharmaceutical composition according to.
(5) The medicament according to any one of (1) to (4), wherein the ratio of fucoidan and mash vinegar is 1 to 9 parts by weight of fucoidan with respect to 1 part by weight of fucoidan. Composition.
(6) The pharmaceutical composition according to any one of (1) to (5), wherein fucoidan is acetyl fucoidan.
(7) A method for suppressing the growth rate of tumor cells, which is characterized by suppressing the growth rate of tumor cells with a substance obtained by mixing fucoidan and mash vinegar separated from seaweed. In particular, mixing acetyl fucoidan separated from Okinawa mozuku with mash vinegar has the effect of reducing expensive acetyl fucoidan and substituting cheap mash vinegar.
(8) It is a tumor cell growth rate inhibitor characterized by suppressing the tumor cell growth rate by a substance in which fucoidan and mash vinegar separated from seaweed are mixed.
(9) The blending amount of the moromi vinegar is 3% to 95%, and the fucoidan is characterized by being derived from seaweeds such as mozuku, wakame, mekabu, kelp, hijiki, akamoku, and sargassum. 7) is the method for suppressing the growth rate of tumor cells.
(10) The blending amount of the moromi vinegar is 3% to 95%, and the fucoidan is characterized by being derived from seaweeds such as mozuku, wakame seaweed, mekabu, kelp, hijiki, and akamoku. The above-mentioned substance that suppresses the growth rate of tumor cells.
(11) The above-mentioned mash vinegar is characterized by being a mash vinegar stock solution and / or a deodorized mash vinegar and / or a mash vinegar powder and / or a deodorized mash vinegar powder, according to (7) or (9). It is a method of suppressing the growth rate of tumor cells in vinegar.
(12) The above-mentioned mash vinegar is characterized by being a mash vinegar stock solution and / or a deodorized mash vinegar and / or a mash vinegar powder and / or a deodorized mash vinegar powder, according to (8) or (10). It is a substance that suppresses the growth rate of tumor cells.

It was found that the pharmaceutical compositions ((1) to (6)) containing fucoidan and mash vinegar of the present invention have an effect of suppressing the growth rate of tumor cells, reduce the amount of fucoidan used, and can be replaced with inexpensive mash vinegar. Since various fucoidans are sufficient instead of acetyl fucoidan, various seaweeds can be used. In particular, when acetyl fucoidan separated from Okinawa mozuku and moromi vinegar are mixed, expensive acetyl fucoidan is reduced and cheap moromi vinegar is used. It has the effect of being a substitute. In addition, since fucoidan and moromi vinegar are not toxic, there are no side effects like conventional chemotherapeutic agents, and the burden of side effects on patients can be reduced. Therefore, mass cultivation is possible and it can be manufactured at low cost.
According to the method of suppressing the growth rate of tumor cells with a substance that is a mixture of fucoidan and mash vinegar separated from seaweed as in (7), as a result of experiments, the amount of fucoidan used can be reduced and inexpensive mash vinegar can be used instead. found. Since various fucoidans are sufficient instead of acetyl fucoidan, various seaweeds can be used. In particular, mixing acetyl fucoidan separated from Okinawa mozuku with mash vinegar has the effect of reducing expensive acetyl fucoidan and substituting cheap mash vinegar.

According to the substance obtained by mixing fucoidan and mash vinegar separated from seaweed as in (8), as a result of the experiment, it was found that the amount of fucoidan used could be reduced and cheap mash vinegar could be used instead.

As in (9), the amount of the above-mentioned vinegar is 3% to 95%, and the above-mentioned fucoidan is derived from seaweeds such as mozuku, wakame, mechabu, kombu, hijiki, akamoku, and sargassum. The range of vinegar used is large, and fucoidan can also be collected from seaweeds other than Okinawa mozuku.

As in (10), the blending amount of the above-mentioned moromi vinegar is 3% to 95%, and the above-mentioned fucoidan is derived from seaweeds such as mozuku, wakame seaweed, mechabu, kelp, hijiki, and akamoku. The width is large, and fucoidan can be collected and used from seaweeds other than Okinawa mozuku.

As described in (11), the above-mentioned mash vinegar is a mash vinegar stock solution and / or a deodorized mash vinegar and / or a mash vinegar powder and / or a deodorized mash vinegar powder and / or a mash cake. The range of adoption is wide, and various raw materials can be adopted.

As described in (12), the above-mentioned mash vinegar is a mash vinegar stock solution and / or a deodorized mash vinegar and / or a mash vinegar powder and / or a deodorized mash vinegar powder and / or a mash cake. The range of adoption is wide, and various raw materials can be adopted.

It is a flowchart which shows the mixing method by this invention.

Unless otherwise specified, the terms used herein and in the claims have the following meanings.

Fucoidan Fucoidan (English name: fucoidan) is a type of sulfated polysaccharide. It is a dietary fiber that is abundant in the mucilage of brown algae such as kelp, wakame seaweed (including mekabu, which is a part of it), and mozuku seaweed. It is a compound in which tens to hundreds of thousands of L-fucose (polysaccharides) are mainly linked by α1-2 and α1-4 bonds, and has an average molecular weight of about 200,000. It is classified into U-fucoidan containing glucuronic acid, F-fucoidan consisting only of sulfated fucose, and G-fucoidan containing galactose. Fucoidan is a general term, and a part of the moromi vinegar undiluted powder is acetyl fucoidan. In the present invention, fucoidan powder purchased from Kinshu Bio Co., Ltd. was used.

Moromi vinegar Moromi vinegar is a liquid obtained by compression-filtering moromi lees produced during the manufacturing process of "Awamori," a distilled liquor produced in Okinawa (Ryukyu Islands). Although it is called moromi vinegar, it is a soft drink that contains almost no acetic acid and is rich in amino acids and citric acid. In the present invention, a powdered moromi vinegar stock solution purchased from the partnership company Niisato Sake Brewery was used.

Pharmaceutical Composition Containing Fucoidan and Moromi Vinegar The pharmaceutical composition of the present invention can be produced by mixing a concentrated powder or undiluted solution prepared from a stock solution of moromi vinegar with fucoidan powder. The ratio of fucoidan and moromi vinegar can be adjusted so as to maximize the effect of suppressing the growth rate of tumor cells. The ratio of fucoidan to moromi vinegar is 1 to 9 parts by weight, preferably 1 to 3 parts by weight, and more preferably 1 part by weight with respect to 1 part by weight of fucoidan. The pharmaceutical composition of the present invention is preferably a pharmaceutical composition for oral administration. Further, the pharmaceutical composition for oral administration of the present invention may be a powder, a paste, a tablet liquid or, preferably a powder, a paste, or a tablet. The solid preparation of the present invention is preferably further encapsulated or coated on the surface. The encapsulated preparation and the coating preparation can be produced by using a known method.

Next, the antitumor effect as a result of mixing acetyl fucoidan derived from Okinawa mozuku and moromi vinegar will be described in detail. As a result of the experiment, the yield of acetylfucoidan is as follows. The yield of acetyl fucoidan isolated from Okinawa mozuku is shown in Table 1. 2.3% crude polysaccharide was obtained from the wet algae. Purification of this crude polysaccharide gave a purified polysaccharide in a yield of 2.0%. These numbers are higher than the conventional results. However. Okinawa mozuku contains only a small amount of alginic acid (1/10), and most of the macromolecules contained in the algae can be said to be acetylfucoidan.

Therefore, in general, only 35% of the acetyl fucoidan present in Okinawa mozuku can be extracted from the algae. Compared with other brown algae (kelp, wakame seaweed and hijiki: the content of these fucoidans is 1/3 of alginic acid), it can be seen that Okinawa mozuku contains extremely high content of fucoidan. From the viewpoint of fucoidan content, it can be seen that Okinawa mozuku is a very peculiar seaweed.

アセチルフコイダンの全糖、ウロン酸および硫酸含量をフェノール硫酸、カルバゾール硫酸およびゼラチン懸濁法で分析した結果を表２に示した。本多糖の全糖、Ｄ- グルクロン酸および硫酸含量は、それぞれ66.9% 、14.1% および15.8％であった。
アセチルフコイダンの構成成分は次のとおりである。
アセチルフコイダンの化学構成を表２に示す。

アセチルフコイダンを2.0 Ｍの硫酸で加水分解（100 ℃、2 時間）を行い、炭酸バリウムで中和した後、濃縮して高速液体クロマトグラフ（ＤＸ500 ：ダイオネックス社）で構成糖の分離・同定を行った。液体クロマトグラムから、Ｌ- フコースとＤ- キシロースを同定した。ほとんどがＬ- フコースで構成される多糖である事が分かる。 The northern limit of the growth of Okinawa mozuku is the Amami region of Kagoshima prefecture, and the southern limit is Ishigaki island of Okinawa prefecture. From these characteristics, it can be understood that Okinawa mozuku is a biological resource that Okinawa Prefecture is proud of in the world.
The yield of acetylfucoidan is shown in Table 1.

Table 2 shows the results of analyzing the total sugar, uronic acid and sulfuric acid contents of acetylfucoidan by the phenol sulfuric acid, carbazole sulfuric acid and gelatin suspension method. The total sugar, D-glucuronic acid and sulfuric acid contents of this polysaccharide were 66.9%, 14.1% and 15.8%, respectively.
The components of acetylfucoidan are as follows.
The chemical composition of acetylfucoidan is shown in Table 2.

Hydrolyze acetylfucoidan with 2.0 M sulfuric acid (100 ° C, 2 hours), neutralize with barium carbonate, concentrate, and separate and identify the constituent sugars with a high performance liquid chromatograph (DX500: Dionex). went. L-fucose and D-xylose were identified from the liquid chromatogram. It can be seen that most of them are polysaccharides composed of L-fucose.

From this result and the results of other chemical analyzes, the components of fucoidan and their ratios were L-fucose: D-xylose: D-glucuronic acid: acetic acid: sulfuric acid = 4.0: 0.1: 1.0: 1.0: 1.0. In 1996-7, Okinawa mozuku was the only fucoidan to replace the acetic acid group. From this point as well, it can be seen that the fucoidan is extremely peculiar. In addition, other mozuku, kelp and hijiki have a high content of sulfate groups (30-35%). The constituent sugars are also diverse, and it is known that they contain D-galactose, D-glucose, etc. in addition to the constituent sugars contained in Okinawa mozuku.

Regarding the antitumor activity of acetylfucoidan: Table 3 shows the growth inhibitory effect of acetylfucoidan on U937 cells. The measured value of the culture solution of U937 cells to which only distilled water was added was set as 100 (control), and% was displayed. A preliminary experiment on the amount of addition was carried out, and this experiment was carried out under the following conditions (3 types).
When 500 μg of acetylfucoidan alone was added, the growth rate of tumor cells decreased to 80%. When only moromi vinegar was added, it decreased to 90%. The growth rate of the culture medium obtained by mixing the two (250 + 250 μg) decreased to 71%, and a significant synergistic effect was observed. Moreover, when the addition amount of acetylfucoidan and mash vinegar was doubled (total concentration 1000 μg / ml), the growth rates of tumor cells became 70%, 85% and 55%, respectively. Furthermore, when the total amount added was increased to 2000 μg, the growth rate decreased to 65%, 78% and 45%. The same experiment was performed three times, and almost the same results were obtained.
Table 3 shows the growth rate of tumor cells (100% with the addition of distilled water only) by the addition of acetylfucoidan and mash vinegar.

Comparing the solution to which only acetylfucoidan or moromi vinegar was added and the solution to which a mixture of both was added, the antitumor activity of the mixture of both showed a higher reduction rate than that added alone, which is clear. A synergistic effect was observed.

Administration of a mixture of acetylfucoidan isolated from Okinawa mozuku and moromi vinegar was able to suppress the growth rate of tumor cells. Moreover, since moromi vinegar is cheaper than acetyl fucoidan, it is easy to obtain and can be expected to be put into practical use.

1 Acetyl fucoidan 2 Moromi vinegar 3 Mixture

Claims (1)

A pharmaceutical composition for treating tumors containing fucoidan and moromi vinegar.

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