JP2005179193A - Vegetable antitumor agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To find out a new vegetable antitumor agent and to provide a food additive and a healthy food comprising a new vegetable antitumor ingredient. <P>SOLUTION: The antitumor agent, food additive and healthy food comprise dried powder of at least one or more species of plant bodies selected from the group consisting of Artemisia campestris L., Limonium wrightii O. kuntze and Peucedanum japonicum Thunb. or an extract therefrom as an active ingredient. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an antitumor agent of plant origin, food additive and health food useful for the prevention and treatment of cancer.

  Currently, various plants having actions such as antitumor activity, carcinogenesis-inhibiting activity, tumor cell growth-inhibiting activity are known, and are widely used as anticancer agents (also called antitumor agents, anticancer agents), health foods for cancer prevention, etc. It is used.

  For example, Patent Document 1 describes that mugwort, mugwort water extract, oolong tea water extract, bancha water extract, perilla and perilla water extract are effective for the prevention and treatment of cancer. ing.

  In addition, although the anticancer action mechanisms are different from each other, for example, guava (Patent Document 2), bitter gourd (Patent Document 3), turmeric (Patent Document 4), eucalyptus (Patent Document 5) and the like have anticancer effects. It is described that there is.

JP-A-8-3054 JP-A-7-291873 JP 2002-205953 A JP 2002-136267 A JP 2002-306139 A

  An object of the present invention is to find a novel plant antitumor agent.

  Furthermore, an object of this invention is to provide the food additive and health food containing a novel plant antitumor component.

  In order to achieve the above-mentioned object, the present inventors have conducted intensive research and found that Ryukyu mugwort, button bowfish and turmeric islet have an antitumor activity and have completed the present invention.

That is, the present invention
(1) An antitumor agent comprising, as an active ingredient, a dry powder of at least one plant selected from the group consisting of Ryukyu mugwort, turmeric pine, and button-brow fu or an extract thereof;
(2) The antitumor agent according to (1) above, wherein the plant dry powder extract is extracted with water or ethanol;
(3) A food additive containing at least one plant dry powder selected from the group consisting of Ryukyu mugwort, turmeric pine, and button humor or an extract thereof; and (4) Ryukyu mugwort, turmeric pine and button humor. A health food containing a dry powder of at least one plant selected from the group consisting of or an extract thereof is provided.

  According to the present invention, a novel plant antitumor agent, food additive, and health food are provided.

  By ingesting the plant antitumor agent, food additive and health food of the present invention, cancer can be prevented and treated.

Hereinafter, the present invention will be described in detail.
The antitumor agent, food additive, and health food of the present invention contain at least one dry powder of plant selected from the group consisting of Ryukyu mugwort, turmeric pine, and button-blow fuchu or an extract thereof as an active ingredient.

  Ryukyu mugwort (Artemisa campestris L.) is a plant belonging to the family Asteraceae and is sometimes called by dialect names such as Inchingsa and Hama March. This shrub-like perennial plant grows mainly on the coasts of Okinawa Prefecture such as Kumejima, Keramajima, and Okutakejima. Ryukyu mugwort is known to be effective for tonsillitis, jaundice, meteorites, diabetes, kidney disease, etc. ("Okinawa's medicinal herb encyclopedia", co-authored by Shingo Tawada and Fumiko Ota).

  Button bowfish (Peucedanum japonicum Thanb.) Is a plant belonging to the family Aceraceae and is sometimes called by dialect names such as sacna and chomyusa. It is a strong and evergreen three-year-old vegetation that grows naturally on rocky and gravel grounds on the coast of Okinawa Prefecture. It grows in a sunny place on the seaside, reaches a height of about 90 cm, and its stems branch independently. Buttonbow is known to be effective for hypertension, arteriosclerosis, neuralgia, rheumatism, pleurisy, cough, asthma, whooping cough, antipyretic, etc. ("Okinawa Herbal Encyclopedia", Shingo Tawada and Fumiko Ota).

  Turmeric pine (Limoniom wrightii O. kuntze) is a plant belonging to the family Pinaceae, and is sometimes called by dialect names such as galamsam bread, sea urchin, and cypress. It grows naturally on stones that are immersed in seawater or seawater on the southern part of the main island of Okinawa, Miyakojima, Irabu, Shimobe, Ikejima, Yaeyama Ishigaki, Taketomicho Haterumajima, Yonagunijima. Turmeric pine is effective for liver disease, kidney disease, diabetes, neuralgia, cold, etc., and is also known to be useful as a lowering drug ("Okinawa folk medicinal animals and plants", Nirai).

  In the present invention, the “plant” means the above-ground part and root part of the above three kinds of plants such as stems and leaves.

  The manufacturing method of the dry powder of a plant body is not specifically limited, The method normally used in this industry is employable, For example, it can manufacture in the process shown in FIG. A useful part of the plant is collected, washed with water, cut into an appropriate length (about 1 to 15 cm), dried with a hot air dryer at 50 to 70 ° C. for about 8 hours, and then a sogo type grinder ( A dry powder (particle size of about 0.8 mm Pass) is obtained by pulverizing using a mutual industry company.

  The dry powder of the plant may be a single dry powder produced from only one kind of plant, or a mixed dry powder produced from a mixture of a plurality of plants.

  The method for producing the extract of the dry powder of the plant body is not particularly limited, and a method usually used in the art can be adopted. For example, the extraction step shown in FIG. 2 can be used. As a solvent used for extraction, those usually used in the art, for example, alcohols such as water and ethanol are preferable.

  The plant dry powder extract can have properties such as a solution, slurry, and dry powder.

When the dry powder obtained in the step of FIG. 1 is extracted with water, for example, as shown in FIG. 2, 500 to 1500 mL (5 to 15 times amount) of water is added to 100 g of the dry powder, and the room temperature to At 90 ° C., the components were extracted for 15 to 120 minutes after the temperature was raised, centrifuged, and filtered (using ADVANTEC filter paper No5C, etc.) to remove the dry powder extraction residue, and water extract I Get.
Add 500-2000 mL (2-5 volumes) of water to the dry powder extract residue, extract the components in the same way as above, centrifuge and filter to remove dry powder extract residue. A water extract II is obtained. The extraction residue here is discarded.

  The above water extracts I and II are combined and concentrated under reduced pressure using a rotary evaporator (manufactured by SHIMAZU) until the solid content is about 10 to 20% (10 to 20 g / 100 g). If necessary, an excipient (for example, dextrin, etc.) is added (0-30 g for a 10% vacuum concentrate; 0-60 g for a 20% vacuum concentrate) and spray dried. Alternatively, a powdery water extract product is obtained by freeze-drying. The yield of water extract is usually 17-23 g (yield 17-23%) from dry powder 100 g of plant water extract in the case of Ryukyu mugwort, and 7-12 g in the case of turmeric pine, depending on the type of plant. (Yield: 7 to 12%), usually about 23 to 30 g (yield: 23 to 30%) in the case of button-up.

  In the case of ethanol extraction, as shown in FIG. 3, for example, 500 to 1500 mL (5 to 15 times the amount) of ethanol is added to 100 g of dry powder, and the temperature is increased from room temperature to 70 ° C. The components are extracted over ˜120 minutes, centrifuged, and then filtered to remove the dry powder extraction residue to obtain the ethanol extract I.

  Add 500-2000 mL (2-5 volumes) of ethanol to the dry powder extract residue, extract the components in the same manner as above, centrifuge and filter to remove dry powder extract residue. The ethanol extract II is obtained. The extraction residue here is discarded.

  The ethanol extracts I and II are combined and concentrated under reduced pressure using a rotary evaporator (manufactured by SHIMAZU) until the solid content is about 10 to 20% (10 to 20 g / 100 g). If necessary, an excipient (for example, dextrin, etc.) is added (0-30 g for a 10% vacuum concentrate; 0-60 g for a 20% vacuum concentrate) and spray dried. Alternatively, a powdery ethanol extract product is obtained by lyophilization. Depending on the type of plant, the yield of ethanol extract is usually 17-28 g (yield 17-28%) from 100 g of dry powder of plant ethanol extract in the case of Ryukyu mugwort, and usually 8-12 g in the case of turmeric pine ( Yield: 8 to 12%), and in the case of button bow, it is usually about 23 to 30 g (yield 23 to 30%).

  The extraction component of the dry powder may be extracted from a dry powder obtained from one kind of plant, or may be extracted from a mixture of dry powders of a plurality of kinds of plants. Moreover, what was extracted from said mixed dry powder may be used.

  The plant powder obtained as described above or an extract thereof has antitumor activity and can be used as an antitumor agent, as shown in Test Examples described later.

  Examples of the administration form when the dry powder of the plant of the present invention is administered as a plant antitumor agent include tea (decoction), powder, tablets, granules, capsules and the like. Moreover, in the case of the extract of the dry powder of a plant body, a solution, a tablet, a granule, a retort pouch, a capsule etc. are mentioned. These dosage forms can be produced using techniques, devices, additives and the like known in the art. The flowchart which shows the manufacturing process of a granule, a tablet, a retort pouch, and a capsule to FIGS. 4-7 is shown.

  As a method for administering the plant antitumor agent of the present invention, the above-mentioned form is preferably administered orally.

  As for the acute toxicity of the plant antitumor agent of the present invention, 5 g / kg of each of three types of extracts of turmeric isopine, Ryukyu mugwort, and button fountain (without addition of excipients such as dextrin) are administered. As a result of observing whether or not death was observed by 24 hours, the mice were not observed dead, and the LD50 of the above three types of extracts was 5 g / kg or more. This value corresponds to a person weighing 60 kg taking 300 g of extract at a time, and is considered to be highly safe for the human body and not to exhibit toxicity after oral administration.

  The plant antitumor agent of the present invention can contain various nutritional components, medicinal components, and the like as additional components that can improve the antitumor activity of the dried plant powder or the extract thereof.

  The food additive of the present invention is added as an additive component to various foods, and is taken together with various foods to exhibit antitumor activity. The food to which the food additive of the present invention is added is not particularly limited, and examples thereof include cookies, noodles, soft drinks, cereals, snacks, and dressings.

  The health food of the present invention itself is ingested as a food and exhibits antitumor activity. The health food of the present invention can be made into various forms such as powders, tablets, capsules and the like using a method commonly used in the art.

  The antitumor agent, food additive and health food of the present invention have antitumor activity and are useful for the prevention and treatment of cancer.

  Hereinafter, the present invention will be described more specifically by describing examples and test examples.

Example 1: Production of dry powder water extract of plant
(1) 100 g of dry plant powder of Ryukyu mugwort is put in a rotary evaporator (manufactured by SHIMAZU), 900 mL of water is added, the temperature is raised to 90 ° C., extraction is performed for 60 minutes, and the extraction residue is removed by filtration. An aqueous extract I of Ryukyu mugwort was obtained. 870 mL of water was added to the extraction residue, and extraction was performed again under the same conditions as above to obtain a water extract II of Ryukyu mugwort. The obtained water extracts I and II were combined, concentrated on a rotary evaporator at a temperature of 70 ° C. until the solid content reached about 20%, freeze-dried (manufactured by EYELA), and dried powder of Ryukyu mugwort water extract. 22 g was obtained.

(2) In the above (1), except that the amount of water added to the extraction residue was 751 mL, 27.5 g of the water extract dry powder was also obtained for the dry powder of the button bud plant as in (1) above. Obtained.
(3) In the above (1), except for the addition amount of water to the extraction residue was 750 mL, the dried turmeric plant powder was the same as the above (1) in the same manner as in the above (1). Got.

Example 2: Production of dry powder ethanol extract of plant body
(1) 100 g of dry plant powder of Ryukyu mugwort is put in a rotary evaporator (manufactured by SHIMAZU), 900 mL of 50% ethanol is added, the temperature is raised to 70 ° C., extraction is performed for 60 minutes, and the extraction residue is filtered. After removal, an ethanol extract I of Ryukyu mugwort was obtained. To the extraction residue, 750 mL of 50% ethanol was added, and extraction was performed again under the same conditions as above to obtain an ethanol extract II of Ryukyu mugwort. The obtained ethanol extracts I and II were combined and concentrated on a rotary evaporator at a temperature of 70 ° C. until the solid content was about 20%, and lyophilized to obtain 19.5 g of dry powder of Ryukyu mugwort ethanol extract. It was.

(2) In the above (1), except for the addition amount of 50% ethanol to the extraction residue was changed to 700 mL, 23 g of ethanol extract dry powder was obtained in the same manner as in (1) above.

(3) In the same manner as in (1) above, except that the amount added to the extraction residue in the above (1) was 700 mL, 10.3 g of ethanol extract dry powder was obtained in the same manner as in (1) above.

Test Example: Measurement of anti-tumor activity of water extract of plant This test was carried out according to the procedure shown in FIG.
(1) Antitumor activity against HL-60 tumor cells Pre-cultured HL-60 tumor cells were centrifuged at 800 rpm for 2 minutes, the cells were washed twice with PBS (-), and 10% FCS (fetal calf The cell concentration was adjusted in RPMI 1640 medium (Gibco) supplemented with serum (manufactured by Biofluids) to prepare a cell suspension.

  The three plant aqueous extracts produced in Example 1 above were dissolved in PBS (−) to concentrations of 0.625, 1.25, 2.5, 5.0, and 10.0 mg / mL, respectively. Thus, it added to the cell suspension to make a sample solution.

In a 96-well microplate, 180 μL of the cell suspension is seeded so as to be 1.0 × 10 ⁴ cells / well, and 20 μL of the sample solution with each concentration is added, respectively, at 37 ° C. in a 5% CO ₂ atmosphere. After culturing for 3 days, 2- (4-Lodophenyl 9-3- (4-nitrophenyl) -5- (2,4-disulfophenyl) -2H-tetrazolium monosodium salt (2- (4-lodophenyl) -3- (4-nitrophenyl) -5- (2,4-disulfophenyl) -2H-tetrazolium, monosodium salt; WST-1) and 1-methoxy-5-methyl-phenazinium methyl sulfate (1-Methoxy-5-methyl) After adding 20 μL of a mixed solution with -phenazinium methylsulfate (PMS) and culturing at 37 ° C. in a 5% CO ₂ atmosphere for 3 hours, the mixture was stirred with a microplate mixer (manufactured by NISSIN), and a microplate reader (Bio-TEK) Made at 450 nm The intensity was measured to determine the survival rate of tumor cells. The results are shown in the graph of FIG.

  From the results shown in FIG. 9, it was revealed that the water extract of Ryukyu mugwort, button-brow fu, and turmeric pine plants had antitumor activity.

  It can be seen that turmeric pine can suppress HL-60 tumor cells to 20% or less with a low addition amount of 0.625 mg / mL, and can further strongly suppress to 10% or less with an addition amount of 1.25 mg / mL.

  It can be seen that Ryukyu mugwort can also suppress HL-60 tumor cells to about 20% at a low addition amount of 1.25 mg / mL, and can further strongly suppress to about 10% or less at an addition amount of 2.5 mg / mL.

  For button fountains, HL-60 tumor cells can be strongly suppressed to about 10% at an addition amount of 10.0 mg / mL, but at an addition amount of 5 mg / mL or less, the survival rate of HL-60 tumor cells is reversed. The result showed that the number of The reason why the absorbance increased at a concentration of 5.0 mg / mL or less is unknown.

(2) Antitumor activity against K-562 tumor cells Antitumor activity against K-562 tumor cells was measured in the same manner as in (1) above except that the used tumor cells were changed to K-562. The results are shown in the graph of FIG.

  From the results of FIG. 10, Ryukyu mugwort can suppress K-562 tumor cells to about 40% at a low addition amount of 0.625 mg / mL, and is strong up to 10% or less at an addition amount of 1.25 mg / mL. It can be seen that it can be suppressed.

  It can be seen that turmeric pine can strongly suppress K-562 tumor cells to 10% or less with a low addition amount of 0.625 mg / mL.

  For button fountains, K-562 tumor cells can be strongly suppressed to about 10% at an addition amount of 10.0 mg / mL, but the survival rate of K-562 tumor cells at an addition amount of 5.0 mg / mL or less. On the other hand, the results showed that it increased. The reason for this is the same as described for the HL-60 tumor cells.

  According to the present invention, new plant antitumor agents, food additives and health foods are provided.

FIG. 1 is a flowchart showing a process for producing a plant dry powder. FIG. 2 is a flowchart showing a process for producing a water extract of a dry plant powder. FIG. 3 is a flow chart showing a production process of an ethanol extract of a dry plant powder. FIG. 4 is a granulation flow diagram of a dry powder of a plant body or an extract thereof. FIG. 5 is a tableting flow diagram of a dry powder of plant or an extract thereof. FIG. 6 is a flow chart of retort pouching of a dried plant powder or an extract thereof. FIG. 7 is an encapsulation flow diagram of a dried plant powder or an extract thereof. FIG. 8 is a flowchart showing the procedure of the method for measuring antitumor activity. FIG. 9 is a graph showing the cell growth inhibitory effect of plant body water extract on HL-60 tumor cells. FIG. 10 is a graph showing the cell growth inhibitory effect of plant body water extract on K-562 tumor cells.

Claims (4)

  An antitumor agent comprising, as an active ingredient, a dry powder of at least one kind of plant selected from the group consisting of Ryukyu mugwort, turmeric pine, and button bow fu or an extract thereof.   The antitumor agent according to claim 1, wherein the extract of the dry powder of the plant is extracted with water or ethanol.   A food additive comprising a dry powder of at least one plant selected from the group consisting of Ryukyu mugwort, turmeric pine, and button-brow fu or an extract thereof.   A health food comprising at least one dry powder of a plant selected from the group consisting of Ryukyu mugwort, turmeric pine, and button bow fu or an extract thereof.

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