JP4800687B2 - Antitumor agent and health food containing the same - Google Patents

Description

  The present invention relates to an antitumor agent and a health food containing the antitumor agent, and in particular, an antitumor agent exhibiting a remarkable antitumor effect in both oral administration and direct administration to tumor cells, and such an antitumor agent. In addition, the present invention relates to a health food for maintaining human health, which exhibits excellent antitumor action.

  Traditionally, mushrooms represented by Sarnosh mushrooms have been widely used as traditional Chinese medicines because of their medicinal properties such as diabetes, hypertension, heart disease and liver disease, as well as nutritional tonic, in addition to tumors. ing. In particular, the hot water extract has been shown to have an excellent antitumor effect when taken orally, but it is also found to be less effective when directly acting on tumor cells. ing.

  On the other hand, the applicant of the present application previously described in Japanese Patent Application Laid-Open No. 2003-199530, an extract of bamboo obtained by extracting bamboo such as grown bamboo or its young shoots such as camellia with an alcohol solution is an excellent antitumor agent. It was clarified that it has an action. Thus, an anti-tumor agent comprising such bamboo extract as an active ingredient exhibits a marked anti-tumor effect when directly acting on tumor cells (intratumoral administration), but its oral intake In this case, it was revealed that although some antitumor effect was exhibited, the effect was not sufficient.

  As described above, the hot water extract and bamboo extract, which are conventionally known, such as sarcoma moss, have an excellent effect in the antitumor action in either oral administration or intratumoral administration. In other words, both the oral administration and the intratumoral administration could not exert its excellent action or effect.

JP 2003-199530 A

  Here, the present invention has been made in the background of such circumstances, and the problem to be solved is that it can exhibit a remarkable antitumor effect in both oral administration and direct administration to tumor cells. An object of the present invention is to provide an antitumor agent and a health food containing the same, which assists in maintaining and improving human health.

  Thus, as a result of intensive studies by the present inventors to solve the above-mentioned problems, a hot water extract of sarno mushroom or mushroom that has been conventionally used alone and the bamboo previously proposed by the applicant of the present application. Focusing on the action of these extracts, combining these two kinds of extracts together allows a synergistic improvement effect in the antitumor action to be realized, and the remarkable antitumor effect is given orally. It became clear that it can be effectively exerted both in administration and in direct administration to tumor cells.

Therefore, the present invention has been completed based on such knowledge, and the gist thereof is that both an alcohol extract of bamboo and a hot water extract of Meshimakobu are included as active ingredients. An antitumor agent characterized by the above.

In the present invention, the bamboo alcohol extract and the hot water extract of Meshimakobu are advantageously contained in a ratio (weight ratio) of 2: 8 to 8: 2. .

Further, the present invention is characterized in that the antitumor agent as described above, specifically, the bamboo alcohol extract and the hot water extract of Meshimakobu constituting it are contained as health food components. The health food is also the target.

Thus, in the antitumor agent according to the present invention, together with the bamboo alcohol extract, the hot water extract of Meshima Cobb is contained together, so that it is excellent based on the interaction of these two components. The antitumor effect can be exerted synergistically, and it exhibits remarkable antitumor effect in both oral administration and direct administration to tumor cells, and is therefore advantageous as a therapeutic agent for tumors. It can be used.

In addition, according to the present invention, in a health food containing both components of such an antitumor agent, specifically, bamboo alcohol extract and hot water extract of Meshimakobu , If taken orally on a daily basis, the progression of the tumor (cancer) can be effectively prevented, or the lesion can be effectively improved.

  By the way, the bamboo extract used in the present invention is generally an extract obtained by using a well-known bamboo as a raw material and extracting it according to a normal extraction procedure using an appropriate extraction solvent. However, the bamboo as the raw material is, for example, light bamboo, true bamboo, Munetake bamboo, black bamboo, Yatake, meme, bambutari (origin: Indonesia), etc. Even bamboo is acceptable. Furthermore, the grown bamboo may, of course, be a bud that is a young bud, and may be either a cocoon or whole plant, especially the outer periphery of a bamboo shoot. Is particularly preferably used. Bamboo should be fresh as much as possible, less than one year after harvesting, except for bamboo. In the case of bamboo, it is desirable to extract it immediately after harvesting. However, in any case, it can be used after a long period of time if it is stored frozen while it is fresh.

  As an extraction solvent for extracting such bamboo, acetone, heptane, hexane, cyclohexane, carbon tetrachloride, chloroform, dichloromethane, methyl acetate, ethyl acetate, butyl acetate, acetonitrile, glycerin, toluene, diethyl ether, petroleum ether Organic solvents for extracting oil-soluble substances, such as o-xylene, m-xylene, p-xylene, 1-butanol, t-butanol, 1-propanol, 2-propanol, methanol, etc. are preferably used, and so on Oil-soluble extract obtained by extraction with a suitable solvent, especially an extract obtained by using acetone as an extraction solvent (acetone extract) should be advantageously used particularly as it can remarkably suppress the growth of tumor cells. It becomes.

  As the bamboo extraction solvent, in addition to those exemplified above, alcohols such as ethanol and aqueous solutions thereof, for example, alcohol aqueous solutions having an alcohol concentration of about 50 to 70%, which were clarified in the previous application by the present inventors, etc. Can be used, and bamboo alcohol extract obtained thereby can also be used in the present invention.

  The extraction operation of bamboo using such an extraction solvent can be performed in the same manner as the conventional extraction operation. For example, first, bamboo as a raw material is washed with water to remove foreign substances, and then pulverized. The final size is about 3 to 5 mm, or the size that passes through a screen having a diameter of about 10 mm. Then, the pulverized product having such a size is immersed in an extraction solvent as described above, and the extraction is performed. The immersion is continued until a sufficient color appears in the solution. The period is generally about 6 months at room temperature, but it is different for each extraction solvent, and when heated, the extraction time can be shortened, for example, It is possible to obtain a sufficient extract in the immersion / extraction time of about 1 to 2 hours, but this also determines the time or period effective for extraction for each extraction solvent. It will be.

  Subsequently, the obtained extract is subjected to solid-liquid separation in a centrifuge, and the liquid phase is recovered and concentrated, and then the concentrated bamboo extract is shaped with an equal amount of solid content. The agent is added and dried by freeze drying, and the target bamboo extract is taken out as a powder.

  Here, as the excipient used to powder such bamboo extract, any known one can be appropriately selected and used, for example, kaolin, Talc, light anhydrous silicic acid, wheat starch, rice starch, crystalline cellulose, powdered cellulose, dextrin, lactose, anhydrous lactose, potato starch, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, calcium dihydrogen phosphate, oxycell (cellulose oxide ), Fructose, carmellose, xylitol, D-sorbitol, low substituted hydroxypropylcellulose, corn starch, sucrose, purified sucrose, hydroxypropylcellulose, povidone, D-mannitol, pregelatinized starch, crospovidone, crystalline cellulose carmellose sodium , Crystalline cellulose ( ), Hydroxypropyl starch, glucose hydrate, partially pregelatinized starch, can be exemplified a powder hydrogenated maltose starch syrup and the like.

  On the other hand, in accordance with the present invention, the hot water extract of sarcoma or mushrooms used in combination with the bamboo extract as described above is extracted with normal hot water for the sorghum and mushrooms to be extracted. It is obtained by performing an operation, and as a mushroom, for example, it forms a fruiting body mainly composed of basidiomycetes and ascomycetes belonging to fungi such as agarisk, maitake, hanabiratake, yamabushitake, shiitake, A mycelium or fruit body or a part thereof is used. In addition, the peripheries and so-called Sarnokoshika of the hard perennials of basidiomycete of the basidiomycetes such as Mesima Kobu, Ganoderma, Ganoderma radish, Kofukitake, Chaga, Kawaratake, etc. Either of these is used as a raw material and is extracted with hot water.

  In addition, the hot water extraction operation specifically includes, for example, crushing sarcophagus mushrooms and mushrooms to a size of about 3 to 5 mm square, and then adding water to perform heat extraction for about 1 to 10 hours. As a result, an extract is formed, and after solid-liquid separation with a centrifuge, the liquid-phase extract is concentrated. At that time, the heating extraction time is appropriately selected according to the type of raw material (mushrooms such as Sarno mushrooms), the heating temperature, and the concentration of the target extraction component. Further, the extract liquid concentrated by the above-described concentration operation is further added with the same amount of excipients as exemplified above in the solid content, and further powdered according to the spray drying method and the like. It will be done.

  And the antitumor agent according to this invention and the health food containing the same are obtained by mixing the bamboo extract (powder) obtained in this way and the hot water extract (powder) of Sarno mushroom or mushroom. In this case, the mixing ratio of the bamboo extract and the hot water extract of the moss mushroom or mushroom is appropriately determined according to the purpose and is not particularly limited. Bamboo extract: Sarno mushroom / mushroom hot water extract will be determined in the range of 2: 8-8: 2 by weight ratio.

  Moreover, in the present invention, by using a mixture obtained by mixing both the bamboo extract and the hot water extract of sarno mushroom or mushroom, or by sequentially blending these extracts, The anti-tumor agent and health food formed by the coexistence of these two types of extracts will form, but the forms of these anti-tumor agent and health food include solids, powders, granules, liquids, etc. An appropriate form is selected according to the purpose. For example, when an antitumor agent is used as an injection, it is prepared in a liquid form in the same manner as a conventional injection. In addition, in the case of health foods, bamboo extract and hot water extract of sarcophagus or mushroom can be used as they are, and these extracts can be added to and blended with food ingredients, starch and vitamins. Or the like and other ingredients, and finished into a desired form of health food.

  In addition, the dose and intake of the antitumor agent according to the present invention and health food containing the same are generally about 200 to 600 mg / person for adults per day, although there is no particular limitation.

  Examples of the present invention will be shown below to clarify the present invention more specifically. However, the present invention is not limited by the description of such examples. Needless to say. In addition to the following examples, the present invention includes various modifications based on the knowledge of those skilled in the art without departing from the spirit of the present invention, in addition to the specific description described above. It should be understood that modifications, improvements, etc. can be made. In the following examples, all parts, ratios and percentages are shown on a weight basis unless otherwise specified.

Example 1
The bamboo was washed with water to remove foreign substances and then pulverized to finally obtain a pulverized product of 3 to 5 mm. Then, 10 times the amount of 60% alcohol aqueous solution was added to the pulverized product, and the extraction operation was performed by heating at a temperature of about 60 ° C. for 2 hours. By separating the solution into solid and liquid, an alcoholic extract is obtained, further concentrated, added with an equal amount of excipient (cyclodextrin), and dried by freeze-drying. An alcohol extract powder was obtained.

  On the other hand, mesimacob (Sarnokoshikake) was used and pulverized to obtain pulverized mesimacob having a size of 5 mm or less. Then, 10 times the amount of purified water is added to the pulverized product, and after immersion for 16 hours, the extraction operation is carried out at a temperature of 80 ° C. for 4 hours, and then concentrated by filtration. An excipient (cyclodextrin) was added and spray-dried to obtain a powder of Meshimakobu hot water extract.

  And in order to confirm the antitumor effect by oral administration of this invention product, the following samples 1-4 were prepared as a mouse breeding feed using the bamboo alcohol extract and Meshimakobu hot water extract which were prepared above. . Sample 1 is a bamboo alcohol extract blended feed, which is obtained by mixing bamboo alcohol extract in a proportion of 1% with normal feed for mice: laboratory low dent diet (product of Japan SLC Co., Ltd.), Sample 2 is a mashimakobu hot water extract-containing feed, and the above lab diet is mixed with the mashimakobu hot water extract at a rate of 1%. Sample 3 is a feed containing the product of the present invention, in which the bamboo alcohol extract and Meshimakobu hot water extract are mixed at a ratio of 1: 1, and the mixture (product of the present invention) is mixed with the above-described normal feed. (Laboratory Rodent Diet) mixed at a rate of 1%. In addition, the sample 4 is a control and is only a normal feed (laboratory rodent diet) in which the above-mentioned extract is not blended at all.

In the mouse experiment, a 5-week-old male ICR mouse (Japan SLC Co., Ltd.) was used, which was preliminarily raised for 1 week with a normal diet (laboratory rodent diet), and then ascites was subcutaneously injected into the right lower abdomen. 2.0 × 10 ⁶ cells / head of cancer cells (sarcoma-180) were transplanted and reared. The animal breeding room conditions were constant temperature (24 ° C. ± 1 ° C.) and the light / dark cycle was 12 hours (bright cycle: 6 o'clock to 18 o'clock) throughout the experiment.

  Then, 2 weeks after the transplantation, each group was divided into 10 animals. Further, after this grouping, each group of mice was allowed to freely take any of the previously prepared samples 1 to 4 for 28 days. The tumor area of each mouse was determined by measuring the major and minor diameters every few days with calipers and multiplying them.

  The results of the tumor area resulting from the ingestion of Samples 1 to 4 obtained in this way are shown in FIG. 1. As is clear from this, the group to which the feed containing the product of the present invention (Sample 3) was given is usually Of course, when the diet (sample 4) was given, the tumor area was higher than the group that ingested the feed (sample 1 and sample 2) each containing the bamboo alcohol extract or the hot water extract of Mishima Kob alone. The expansion is effectively suppressed, and even from this, it is confirmed that the product of the present invention exhibits an excellent antitumor effect.

Example 2
Bamboo extract powder (sample 5) and Messimacob hot water extract liquid (sample 5) and Messimacob hot water extract liquid (sample 5) and bamboo shoot powder prepared in Example 1 were dissolved in purified water to form aqueous solutions. Sample 6) was prepared. In addition, the bamboo extract powder and Messimacob hot water extract powder are mixed at a ratio of 1: 1 to obtain the product of the present invention, which is dissolved in purified water to obtain an aqueous solution. (Sample 7) was prepared.

And in order to confirm the direct anti-tumor effect with respect to the tumor cell of this invention product, each sample 5-7 prepared above is each sterilized-filtered, and this invention which is each extract or its mixture by final concentration. The product was added to EME · M medium (10% FBS) (Dainippon Pharmaceutical Co., Ltd.) so that the solid content of the product was 100 or 200 μg / mL. Next, 2.5 × 10 ³ cells / well of each sample-containing medium and ascites tumor cells (sarcoma-180) were dispensed into a 96-well microplate and cultured in a carbon dioxide incubator for 48 hours. Further, after such culturing, 10 μL of Cell Counting Kit-8 (manufactured by Dojindo Laboratories Co., Ltd.) is added to each well, and coloring is performed for 4 hours in a carbon dioxide incubator. Reaction was performed. After this color reaction, absorbance at 450 nm was measured using a microrate reader, and the growth inhibition rate (%) of tumor cells at each concentration of each sample was determined. The result is shown in FIG.

  In the tumor cell growth inhibition rate of each sample shown in FIG. 2, sample 7 (200 μg / mL) to which the product of the present invention was added 200 μg / mL, sample 5a (100 μg / mL) to which bamboo extract was added 100 μg / mL. ), And the inhibition rate of Sample 6a (100 μg / mL) to which 100 μg / mL of the Meshimakobu hot water extract was added was 97.5%, 92.2%, and 50.3%, respectively. It is understood that the inhibitory effect on the growth of tumor cells can be effectively enhanced by using the sample 7a in a mixed form of 6a. In addition, the sample 7 (200 μg / mL) was compared with the sample 5b (200 μg / mL) containing 200 μg / mL bamboo extract and the sample 6b (200 μg / mL) containing 200 μg / mL hot water extract. Moreover, it can also be recognized that the antitumor effect of these extracts is synergistically enhanced by using the present invention compounded by combining the bamboo extract and the hot water extract of Meshimakobu.

  And from the result of above-mentioned Example 1 and Example 2, in the product of the present invention, an antitumor effect is exhibited by oral ingestion by mixing an extract of sarcophagus or mushroom and a bamboo extract. Therefore, it was revealed that even when directly acting on cells, it has a strong antitumor effect, and therefore the product of the present invention is not only used as a health food or an oral antitumor agent, but also as an injection. As described above, by directly acting on the affected area, the effect of preventing or improving the progression of cancer can be obtained.

It is a graph which shows the relationship between the breeding days of the mouse | mouth which the sample 1-4 obtained in Example 1 was given, and a tumor area. 4 is a graph showing tumor cell growth inhibition rates in various samples obtained in Example 2. FIG.

Claims (2)

  An antitumor agent comprising both an alcohol extract of bamboo and a hot water extract of Meshima Cobb as active ingredients. The antitumor agent according to claim 1, wherein the bamboo alcohol extract and the hot water extract of Meshimakobu are contained in a weight ratio of 2: 8 to 8: 2.

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