JPWO2017164411A1 - Antitumor method or substance mixed with fucoidan and rag vinegar - Google Patents

Abstract

[PROBLEMS] To realize a technique capable of further suppressing the growth rate of tumor cells by mixing and administering inexpensive moromi vinegar.
[Solution] The growth rate of tumor cells is suppressed by a substance obtained by mixing fucoidan and filthy vinegar isolated from seaweed. In particular, mixing acetyl fucoidan and mashed vinegar isolated from okinawa mozuku has the effect of reducing expensive acetyl fucoidan and substituting it with inexpensive moromi vinegar. The fucoidan is derived from seaweeds such as mozuku, wakame, mekabu, kelp, hijiki, akamoku, hondawara and the like, with the content of the mash being 3% to 95%.
[Selected figure] Figure 1

Description

  The present invention relates to an invention in which fucoidan such as expensive acetyl fucoidan can be reduced and substituted by inexpensive moromi vinegar by a method or substance in which fucoidan and fumigant vinegar are mixed.

  As described in Patent Document 1, in order to provide a health food drink containing mozuku extract which is easy to drink and easy to absorb in the body, mozuku is used as a main component, to which are added moromi vinegar and black sugar and appropriate drinking water. At the same time as stirring, heating and processing, an AC voltage is applied for a certain period of time by an electrostatic induction device, the molecules of the above solution are micronized by electrostatic induction, and then sterilized and treated. Is known. When extracting mozuku extract, ie fucoidan, in addition to the electrostatic induction by the AC high voltage electric field using an electrostatic induction reactor, an electromagnetic alternating magnetic field is simultaneously applied to the moromi vinegar and the mozuku, electrons, atoms There is also known an invention in which fucoidan has a molecular weight which is easily absorbed by the body through action at the molecular level.

  In addition, as disclosed in Patent Document 2, for the purpose of providing a pharmaceutical composition for oral administration for treating a malignant tumor that has developed in the digestive tract containing acetylfucoidan as an active ingredient, it is manufactured using cultured okinawa mozuku as a raw material The weight loss and the increase in the weight of malignant tumors in mice in which colon26 cells, which are cells derived from mouse colon cancer, are transplanted into the intestine to develop colon cancer by dissolving acetylfucoidan in water and orally administering it. Was significantly reduced (P = 0.05).

JP 2008-22787 A Japanese Patent Application Publication No. 2009-185009

However, as in Patent Document 2, acetyl fucoidan is regarded as promising as a pharmaceutical composition for oral administration for treating a malignant tumor that has developed in the digestive tract. However, acetyl fucoidan is extremely expensive, making it difficult to put to practical use for economic reasons.
The technical problems of the present invention focused on such problems, and investigated that the proliferation rate of tumor cells can be further suppressed by administering a mixture of inexpensive moromi vinegar.

  The inventor of the present invention has unexpectedly found that the antitumor activity of the mixed solution of the two solutions is compared with that of the solution added solely with acetyl fucoidan or a solution to which only the mixed solution of the two solutions is added. It was found that it showed a high reduction rate. Then, further studies were made, and the present invention was completed.

That is, the present invention solves the above-mentioned subject by providing the following inventions.
(1) A pharmaceutical composition for treating a tumor, which comprises fucoidan and mash.
(2) A pharmaceutical composition for suppressing the growth rate of tumor cells, which comprises fucoidan and moromi vinegar.
(3) The pharmaceutical composition according to (1) or (2), wherein the fucoidan is derived from seaweed of mozuku, wakame, mekabu, kelp, hijiki, red sea bream and / or hondawara.
(4) The moromi vinegar is characterized by being a moromi vinegar stock solution and / or deodorizing moromi vinegar and / or moromi vinegar powder and / or deodorizing moromi vinegar powder. Pharmaceutical composition as described in-.
(5) The medicine according to any one of (1) to (4), wherein the ratio of fucoidan to mash vinegar is 1 to 9 parts by weight of mash vinegar 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 of suppressing the growth rate of tumor cells, which comprises suppressing the growth rate of tumor cells with a substance obtained by mixing fucoidan and mori vinegar separated from seaweed. In particular, mixing acetyl fucoidan and mashed vinegar isolated from okinawa mozuku has the effect of reducing expensive acetyl fucoidan and substituting it with inexpensive moromi vinegar.
(8) A growth rate suppressant for tumor cells characterized in that the growth rate of tumor cells is suppressed by a substance obtained by mixing fucoidan and mori vinegar isolated from seaweed.
(9) The content of the mash vinegar is 3% to 95%, and the fucoidan is characterized by being derived from seaweeds such as mozuku, wakame, mekabu, kelp, hijiki, akamoku, hondawara, etc. ( It is a method of suppressing the proliferation rate of the tumor cell as described in 7).
(10) The compounding amount of the moromi vinegar described above is 3% to 95%, and the fucoidan is derived from seaweeds such as mozuku, wakame, mekabu, kelp, hijiki, Akamoku, etc., (8) It is a growth rate suppressant of the described tumor cell.
(11) The above-mentioned moromi vinegar is a moromi vinegar stock solution and / or a deodorizing moromi vinegar and / or a moromi vinegar powder and / or a deodorizing moromi vinegar powder, as described in (7) or (9). Is a method of suppressing the proliferation rate of tumor cells.
(12) The above-mentioned moromi vinegar is a moromi vinegar stock solution and / or a deodorizing moromi vinegar and / or a moromi vinegar powder and / or a deodorizing moromi vinegar powder, as described in (8) or (10). Growth rate inhibitors of tumor cells.

The pharmaceutical compositions ((1) to (6) containing fucoidan and mash vinegar according to the present invention have the effect of suppressing the growth rate of tumor cells, and it has been found that the amount of fucoidan can be reduced and substituted by cheap mash vinegar. Not only acetyl fucoidan but also various fucoidans can be used, so various seaweeds can be used, especially when acetyl fucoidan and mashed vinegar isolated from okinawa mozuku are mixed, the expensive acetyl fucoidan is reduced and it is inexpensive moromi vinegar Also, since no fucoidan and no toxic side effect of mojimi vinegar are observed, there is no side effect like conventional chemotherapeutic agents, and the burden of side effects on patients can be alleviated. Therefore, mass culture is possible and can be manufactured inexpensively.
As described in (7), according to the method of suppressing the growth rate of tumor cells with a substance in which fucoidan separated from seaweed and humic vinegar are mixed, as a result of experiment, the amount of fucoidan used can be reduced and substitute with cheap moromi vinegar found. Since not only acetyl fucoidan but also various fucoidans are sufficient, various seaweeds can be used. In particular, mixing acetyl fucoidan and mashed vinegar isolated from okinawa mozuku has the effect of reducing expensive acetyl fucoidan and substituting it with inexpensive moromi vinegar.

  As shown in (8), as a result of experiments based on a mixture of fucoidan separated from seaweed and mash vinegar, it was found that the amount of fucoidan used can be reduced and it can be substituted by inexpensive moromi vinegar.

  As described in (9), the content of the mash is 3% to 95%, and the fucoidan is derived from seaweeds such as mozuku, wakame, mekabu, kelp, hijiki, red sea bream, and so on. The range of use of vinegar is large, and fucoidan can also be collected and used from seaweed other than okinawa mozuku.

  As described in (10), the amount of moromi vinegar is 3% to 95%, and the fucoidan is derived from seaweeds such as mozuku, wakame, mekabu, kelp, hijiki, Akamoku, etc., so use of moromi vinegar The range is wide, and fucoidan can also be collected and used from seaweed other than okinawa mozuku.

  As (11), the moromi vinegar is a moromi vinegar stock solution and / or a deodorizing moromi vinegar and / or a moromi vinegar powder and / or a deodorizing moromi vinegar powder and / or a moromi vine, so as the moromi vinegar Adoption range is large, various raw materials can be adopted.

  As (12), the moromi vinegar is a moromi vinegar stock solution and / or a deodorizing moromi vinegar and / or a moromi vinegar powder and / or a deodorizing moromi vinegar powder and / or a moromi vine, so as the moromi vinegar Adoption range is large, various raw materials can be adopted.

5 is a flow chart illustrating a mixing method according to the present invention.

  Unless otherwise stated, the terms used in the specification and claims have the meanings given below.

Fucoidan Fucoidan (English name: fucoidan) is a type of sulfated polysaccharide. It is a dietary fiber that is abundantly contained in mucilage of brown algae such as kelp and wakame (including mekabu which is a part of the order) and mozuku. It is a compound in which several tens to hundreds of thousands of L-fucose (polysaccharide) are 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 generic term, and a part of moromi vinegar stock solution powder is acetyl fucoidan. In the present invention, fucoidan powder purchased from Kinsho Bio Inc. was used.

Moromi vinegar Moromi vinegar is a liquid obtained by compression-filtering a moromi koji produced in the production process of "Awamori" which is a distilled liquor from Okinawa (Ryukyu Islands). It is called moromi vinegar, but contains little acetic acid and is a soft drink rich in amino acids and citric acid. In the present invention, used is a powdered moromi vinegar stock solution purchased from the company Nisato Shuzo.

Pharmaceutical Composition Containing Fucoidan and Fermented Vinegar The pharmaceutical composition of the present invention can be prepared by combining concentrated powder or undiluted solution prepared from undiluted solution of moromi vinegar with fucoidan powder. The proportions of fucoidan and brown vinegar can be adjusted to maximize the effect of suppressing the growth rate of tumor cells. The ratio of fucoidan and mash vinegar is 1 to 9 parts by weight, preferably 1 to 3 parts by weight, and more preferably 1 part by weight of vinegar to 1 part by weight of fucoidan. The pharmaceutical composition of the present invention is preferably a pharmaceutical composition for oral administration. 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. Encapsulated formulations and coated formulations can be manufactured using known methods.

  Next, the antitumor effect as a result of mixing acetyl fucoidan derived from okinawa mozuku with mori vinegar will be described in detail. As a result of the experiment, the yield of acetyl fucoidan is as follows. The yield of acetyl fucoidan isolated from okinawa mozuku is shown in Table 1. The wet algal cells gave 2.3% crude polysaccharide. The crude polysaccharide was purified to obtain a purified polysaccharide in a yield of 2.0%. These figures were higher than the conventional results. However. Okinawa mozuku contains only a small amount of alginic acid (1/10), and most of the polymers contained in algal cells can be said to be acetyl fucoidan.

  Therefore, in general, only 35% of acetyl fucoidan present in okinawa mozuku can be extracted from algal cells. In comparison with other brown algae (comb, wakame and hijiki: the content of these fucoidans is 1/3 of alginic acid), it is found that Okinawamozuku contains a very high content of fucoidan. From the point of view of the fucoidan content, it can be seen that okinawa mozuku is a very unusual seaweed.

In addition, the northern limit of Okinawa mozuku growth is in the Amami region of Kagoshima Prefecture, and the southern limit is Ishigaki Island in Okinawa Prefecture. From these characteristics, it can be understood that Okinawa mozuku is a biological resource that Okinawa Prefecture boasts of the world.
The yield of acetyl fucoidan is shown in Table 1.
The total sugar, uronic acid and sulfuric acid contents of acetylfucoidan were analyzed by a phenol sulfuric acid, carbazole sulfuric acid and gelatin suspension method. The results are shown in Table 2. The total sugar, D-glucuronic acid and sulfuric acid contents of this polysaccharide were 66.9%, 14.1% and 15.8%, respectively.
The constituents of acetyl fucoidan are as follows.
The chemical composition of acetyl fucoidan is shown in Table 2.
Acetyl fucoidan is hydrolyzed with 2.0 M sulfuric acid (100 ° C, 2 hours), neutralized with barium carbonate, concentrated and separated and identified by high-performance liquid chromatograph (DX500: Dionex) went. From the liquid chromatogram, L-fucose and D-xylose were identified. It turns out that most are polysaccharides composed of L-fucose.

  From these results and the results of other chemical analysis, the components of fucoidan and their ratio 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, Fucoidan replacing acetate was the only Okinawa mozuku. From this point of view, it can be seen that the fucoidan is extremely unique. Also, other mozuku, kelp and hijiki have a high content of sulfate groups (30-35%). Constituent sugars are also varied, and it is known that D-galactose, D-glucose and the like are contained in addition to the constituent sugars contained in Okinawan mozuku.

Antitumor activity of acetylfucoidan: The growth inhibitory effect of acetylfucoidan on U937 cells is shown in Table 3. The measured value of the culture solution of U937 cells to which only distilled water was added was indicated as 100 (control) with respect to that. The preliminary experiment of the addition amount was performed, and this experiment was performed on condition of the following (three 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 solution obtained by mixing the two (250 + 250 μg) was reduced to 71%, and a synergistic effect was significantly observed. In addition, when the addition amount of acetyl fucoidan and moromi vinegar was doubled (total concentration 1000 μg / ml), the growth rate of tumor cells became 70%, 85% and 55%, respectively. Furthermore, when the total amount added was increased to 2000 μg, the proliferation rate decreased to 65%, 78% and 45%. The same experiment was performed three times but almost the same results were obtained.
The growth rate of tumor cells by the addition of acetyl fucoidan and moromi vinegar (addition of distilled water only is 100%) is shown in Table 3.

  A comparison of the solution containing only acetyl fucoidan or moromi vinegar and the solution containing the mixture of the two shows that the antitumor activity of the mixture of the two shows a high reduction rate compared to that added alone, and it is clear A synergistic effect was observed.

  Administration of a mixture of acetyl fucoidan and mori vinegar isolated from okinawa mozuku was able to suppress the growth rate of tumor cells. Moreover, since moromi vinegar is cheaper than acetyl fucoidan, it can be easily obtained and can be expected to be put to practical use.

1 Acetyl Fucoidan 2 Moromi Vinegar 3 Mixture

Claims (12)

Pharmaceutical composition for tumor treatment containing fucoidan and mash. A pharmaceutical composition for suppressing the growth rate of tumor cells, which comprises fucoidan and moromi vinegar. The pharmaceutical composition according to claim 1 or 2, wherein the fucoidan is derived from a seaweed of Mozuku, Wakame, Mekabu, kelp, hijiki, Akamoku and / or Hondoiraaceae. The pharmaceutical composition according to claim 1 or 2, wherein the moromi vinegar is a moromi vinegar stock solution and / or a deodorizing moromi vinegar and / or a moromi vinegar powder and / or a deodorizing moromi vinegar powder. The pharmaceutical composition according to any one of claims 1 to 4, wherein the ratio of fucoidan to mash vinegar is 1 to 9 parts by weight of mash vinegar to 1 part by weight of fucoidan. The pharmaceutical composition according to any one of claims 1 to 5, wherein the fucoidan is acetyl fucoidan. A method for suppressing the growth rate of tumor cells, which comprises suppressing the growth rate of tumor cells with a substance obtained by mixing fucoidan and sorghum vinegar isolated from seaweed. A substance for suppressing the growth rate of a tumor cell, which is characterized by suppressing the growth rate of a tumor cell by a substance obtained by mixing fucoidan and filthy vinegar isolated from seaweed. The fucoidan is derived from seaweeds such as mozuku, wakame, mekabu, kelp, hijiki, akamoku, hondawara and the like, with the blending amount of the above-mentioned moromi vinegar being 3% to 95%. Method of suppressing the proliferation rate of tumor cells. The fucoidan is derived from seaweeds such as mozuku, wakame, mekabu, kelp, hijiki, akamoku, hondawara and the like, wherein the amount of the mash is 3% to 95%. Growth rate inhibitors of tumor cells. The above-mentioned moromi vinegar is a moromi vinegar stock solution and / or a deodorizing moromi vinegar and / or a moromi vinegar powder and / or a deodorizing moromi vinegar powder and / or a moromi vine A method for suppressing the proliferation rate of the described tumor cells. 11. The method according to claim 8, wherein said moromi vinegar is moromi vinegar stock solution and / or deodorizing moromi vinegar and / or moromi vinegar powder and / or deodorizing moromi vinegar powder and / or moromi vinegar. The growth rate inhibitor of a tumor cell as described.