JP5008813B2 - Anti-Skin Cancer Agent Containing Cubileta Extract - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a preparation, cosmetic, food, and food additive containing an active ingredient in a millet, and more specifically, a preparation, cosmetic, food containing an antitumor active ingredient And food additives.
[0002]
[Prior art]
In Japan today, the rapid increase in lifestyle-related diseases has become apparent with the westernization of the food environment. As a result, the number of cases in which malignant tumors cause death has been increasing in recent years.
[0003]
Conventionally, various drugs have been used for tumor treatment. In general, many drugs for tumor treatment have strong side effects and are not suitable for long-term use. Therefore, development of pharmaceuticals with few side effects is desired, but until now there have been no actual drugs with few side effects and high therapeutic effects.
[0004]
In addition, from the viewpoint of daily prevention and improvement of tumors, it has been eagerly desired to be in a form added to foods that are easy to ingest and cosmetics that can be used easily, not in the form of pharmaceuticals.
[0005]
Antitumor foods using green algae known so far are disclosed in JP-A No. 11-15068, in which a sugar compound-containing material containing uronic acid and / or a uronic acid derivative is added as an organic acid. There is a processed product heated under wet pressure in the presence of. This heat-treated product contains an active ingredient having cytotoxicity against human promyelocytic leukemia cells, and only onion and roasted tea are disclosed as examples, and its effectiveness has been proved. However, regarding green algae, there is no disclosure regarding the effectiveness, and the active ingredient content is not described. Therefore, not all antitumor activities due to the active ingredients are recognized for green algae.
[0006]
Furthermore, in the antitumor activity evaluation technique disclosed in JP-A-11-15068, toxicity evaluation for normal cells has not been performed, so there is a risk of toxicity to normal cells, and it is used in pharmaceuticals and the like. There were also problems with the risk of side effects that occurred during the treatment of tumors.
[0007]
[Problems to be solved by the invention]
The present invention has been made in view of the above circumstances, and an antitumor active ingredient that is a kind of green algae Iridaceae, that efficiently extracts an antitumor active ingredient contained in cucumber, and has few side effects and can be used for a long period of time. It is an object of the present invention to provide pharmaceutical preparations, cosmetics, foods and food additives.
[0008]
[Means for Solving the Problems]
In order to solve the above problems, the present inventors have an antitumor activity, that is, a selective cytotoxicity evaluation technique that does not affect normal cells and is toxic only to cancer cells, and has an antitumor active component. Searching for natural products, we found that a substance with anti-tumor activity contained in cruciformers can be efficiently extracted by passing through the appropriate processing process of crubbers, a kind of green algae, Iwata family. Completed the invention.
[0009]
That is, this invention provides the formulation, cosmetics, foodstuff, and food additive characterized by including the anti-tumor active component in a millet.
[0010]
The mixing ratio of the millet extract is 0.001 to 30% by mass, preferably 0.05 to 0.5% by mass, based on the total weight of the preparation, cosmetics, food and food additive, as its dry weight. to.
[0011]
The extraction solvent is one or more selected from water, anhydrous or water-containing organic solvent, and preferably a mixture of water and a polar solvent, as a condition that the components contained in the cubet act as antitumor activity. It is a solvent, more preferably a water-containing monohydric alcohol .
[0012]
As a condition that the component contained in the millet acts as an antitumor activity, the drying is hot air drying or spray drying at 30 to 135 ° C., preferably vacuum drying .
[0013]
DETAILED DESCRIPTION OF THE INVENTION
Curlatora (Caulerpa lentillifera J. Agardh), which is a raw material of the present invention, is a seaweed belonging to the family Iwayidae belonging to green algae. This seaweed is eaten regularly in the Okinawa region and is known as a low-calorie food that contains abundant dietary fiber and contains a large amount of calcium, iron, vitamins, minerals, etc. It is not done.
[0014]
The present invention, biological materials dried product or solvent extract of Kubiredzuta of Kubiredzuta, the extraction residue, extraction residue dried product or the like, may be used of any state. At that time, it can be used after being shredded or pulverized as required.
[0015]
The mixing ratio of the cublet extract has an optimum concentration of selective cytotoxicity that is an index of antitumor activity. Therefore, the dry weight is 0.001 with respect to the entire preparation, cosmetic, food and food additive. It is characterized by containing -30 mass%, preferably 0.05-0.5 mass% .
[0016]
As an extraction condition in which the components in the filter act as an antitumor activity, the solvent for extraction of the filter is monohydric alcohol, polyhydric alcohol or derivative thereof, ketone, ester, ether, petroleum, water, anhydrous or hydrous organic solvent. Ether, aliphatic hydrocarbon or halide, aromatic hydrocarbon. These may be used alone or in combination of two or more. Among these solvents, in order to develop foods, it is preferably a mixed solvent of water and a polar solvent, more preferably a water-containing monohydric alcohol, and most preferably water-containing ethanol. To do.
[0017]
The concentration of the water-containing ethanol used for the extraction of the constrictor is not particularly limited, but is preferably a mixed solvent containing 50% or more of water.
[0018]
In the extraction of the cubator, the ratio between the cubator and the extraction solvent is not particularly limited, but a concentration considering the ratio of the density of the cubator and the density of the extraction solvent is preferable. In the case of water-containing ethanol, the dried product of the cubet The solvent is preferably 3 to 1000 times by weight, more preferably 6 to 200 times by weight in terms of extraction operation and efficiency. In addition, the extraction temperature is not particularly limited, but considering that some of the active ingredients are heat-sensitive and easily oxidized, the boiling point of the solvent at room temperature to normal pressure is set. Is convenient. Furthermore, the extraction time is several minutes to 24 hours, preferably 12 to 24 hours. This extraction operation is repeated several times to obtain a higher concentration.
[0019]
As the drying conditions in which the ingredients in the filter act as an antitumor activity, some of the active ingredients are heat-sensitive and easily oxidized, so hot air drying or spray drying at 35 to 135 ° C. Preferably, it is hot air drying at 50 to 65 ° C., and more preferably vacuum drying . In this case, the vacuum drying is more preferably freeze-drying than room temperature vacuum drying.
[0020]
In drying the above-described constrictor, the landed constrictor can be washed several times with fresh water to remove salt, and then dried, or when the extract and its residue are dried.
[0021]
Further, in the extraction of the cruciformer, the edible portion or stem portion dried by hot air drying at 30 to 135 ° C., spray drying or reduced pressure drying can be used by chopping or pulverizing as necessary. The extract of the constrictor can be used as it is or after being diluted. Furthermore, it can be used in any state, such as concentrated extract or dried extract obtained by removing the solvent from the extract. It is preferable to do. In that case, after removing a part of solvent beforehand with a rotary evaporator or a centrifugal evaporator using the boiling point of a solvent, etc., it can dry by 30-135 degreeC hot air drying, spray drying, or reduced pressure drying .
[0022]
In the preparation of the present invention, the extract of the cruciator obtained as described above is combined with a known pharmaceutical carrier as necessary, and oral preparations such as tablets, granules, powders, syrups, suppositories or external preparations. It is prepared by formulating.
[0023]
The pharmaceutical carrier that can be used for the preparation of the preparation of the present invention is not particularly limited, and those commonly used can be used. Examples thereof include starch, lactose, sucrose, mannitol, Solid carriers such as carboxymethylcellulose, corn starch and inorganic salts; liquid carriers such as distilled water, physiological saline, aqueous glucose solution, alcohol such as ethanol, propylene glycol and polyethylene glycol; various animal and vegetable oils, white petrolatum, paraffin, waxes, etc. Oily carriers and the like.
[0024]
The dosage of the preparation of the present invention varies depending on the target tumor, its degree, or the age of the subject, but is 0.0001 mg to 5,000 mg per day as an extract of the millet (amount of dry solid). It is preferable to administer in 1 to 3 divided doses per day.
[0025]
In use as a food or food additive of the present invention, it can be used in various foods in combination with appropriate foods and food additive ingredients, and is not particularly limited, but examples include salmon, troches, and gums. Foods such as yogurt, ice cream, pudding, jelly, yokan, water yokan, coffee drink, juice, carbonated drink, milk, whey drink, lactic acid bacteria drink, cookies, soup and mayonnaise can be prepared.
[0026]
Food raw materials that can be used for food preparation are not particularly limited, and can be appropriately selected according to the type of the product. Examples thereof include glucose, fructose, sucrose, maltose, sorbitol, and stevioside. , Rubusoside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, Sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin B, nicotinamide, calcium pantothenate, amino acids, calcium salts, pigment Perfumes, it may be mentioned those commonly used as food material such as preservatives.
[0027]
For example, in the case of potage soup, the added amount of the constrictor extract in food may be about 0.1 to 50% by mass.
[0028]
EXAMPLES Next, although an Example and a test example are given and this invention is demonstrated in more detail, this invention is not restrict | limited at all by these Examples.
[0029]
【Example】
(Example 1)
The ground fly was washed several times with fresh water for desalination, and then the edible portion of the fly fly was freeze-dried under reduced pressure and crushed by a centrifugal grinder. 1 g of powdered cublet was mixed with 20 ml of 50% ethanol, and shake extraction was performed 290 times per minute under the condition of extraction time of 2 days to obtain 16.5 ml of crumblet extract.
[0030]
(Example 2)
5 ml of the extract obtained in Example 1 was collected and dried. This dried product was redissolved with 1 ml of PBS (−) (pH 7.4), sterilized by filtration through a 0.45 μm sterilizing filter, and used as an added sample, and the cytotoxicity test shown below was performed.
[0031]
In the cytotoxicity test, A-431 (epidermoid carcinoma cells) and CCD-27SK (normal skin fibroblasts) were used as cells. In addition, the survival status of cells can be determined by using the fact that tetrazolium salt (MTT) is converted into a blue formazan product by living cells, and the amount of formazan product produced can be determined by measuring absorbance at 570 nm. A method called “Chemling, BGet al. Leukemia Res. 1988, 12, 823”] was used.
[0032]
Use a 96-well microplate for the test. After preparing a dilution series of the added sample, calculate the cell viability based on comparison with the control test in which PBS (-) (pH 7.4) was added instead of the added sample. did.
[0033]
The results of the cytotoxicity test are shown in FIG. In the figure, o is a survival graph of normal skin fibroblasts, and x is a survival graph of epidermoid carcinoma cells. As is clear from FIG. 1, there is a point where the survival rate of normal skin fibroblasts is high and the survival rate of epidermoid cancer cells is low, and cancer cells are selectively added to the added sample used in the present invention. It was found to contain a killing substance.
[0034]
Further, as is apparent from the results of FIG. 1, it was found that the normal skin fibroblasts survived and the epidermoid cancer cells had the optimal concentration to die by the dilution series. From this result, the mixing ratio of the millet extract of the present invention is 0.001 to 30% by mass, preferably 0.05 to 0.5% by mass, based on the total weight of the preparation, cosmetics, food and food additive, as its dry weight. % Content was determined to be appropriate.
[0035]
(Example 3)
1 kg of the edible portion of the millet was processed in the same manner as in Example 1 using 20 L of 50% ethanol to obtain 16.5 L of an extract. This extract was freeze-dried under reduced pressure to obtain 330 g of a dried product of a constrictor extract.
[0036]
(Example 4)
Tablet: 100 g of the millet extract obtained in Example 3, 100 g of lactose and 4 g of magnesium stearate were mixed, and this mixture was tableted with a single tableting machine to produce a tablet having a diameter of 10 mm and a weight of 300 mg.
[0037]
(Example 5)
Granules: Tablets obtained in Example 4 were pulverized, sized and sieved to obtain 20-50 mesh granules.
[0038]
(Example 6)
cookie:
(Composition) (Parts by weight)
Margarine 30
Sugar 17
Salt 0.003
Whole egg 8.6
Soft flour 43.397
Constrictor extract 1
[0039]
(Example 7)
Potage:
(Composition) (Parts by weight)
Potato 78
Fresh cream 18
Butter 1.7
Salt 0.2
Flour 1.1
Constrictor extract 1
[0040]
【Effect of the invention】
The antitumor foods using green algae known so far include sugar compounds containing substances containing uronic acid and / or uronic acid derivatives disclosed in JP-A No. 11-15068 and added organic acids. There is a processed product heated under wet pressure in the presence of. This heat-treated product contains an active ingredient having cytotoxicity against human promyelocytic leukemia cells, and only onion and roasted tea are disclosed as examples, and its effectiveness has been proved. However, regarding green algae, there is no disclosure regarding the effectiveness, and the active ingredient content is not described. Therefore, not all antitumor activities due to the active ingredients are recognized for green algae. Furthermore, since the disclosed anti-tumor activity evaluation technology has not been evaluated for toxicity to normal cells, there is a risk of toxicity to normal cells, and side effects that occur during the treatment of tumors used in pharmaceuticals, etc. There was also a problem with the danger. Formulations, cosmetics, foods, and food additives using an antitumor active ingredient contained in cucumber, which is a kind of green alga striaceae of the present invention, selectively kill cancer cells without affecting normal cells. Contains substances. As the antitumor active ingredient of the present invention is clear from the fact that this cucumber has been traditionally eaten in the Okinawa region, it has extremely low side effects and extremely high safety. However, it can be used continuously, and can also be added to foods, food additives and cosmetics that can be used on a daily basis. Furthermore, through an appropriate processing step, it was possible to efficiently extract a substance having antitumor activity, that is, selective cytotoxicity, contained in the filter . As a result, elderly people whose physical functions have decreased due to aging and whose disease risk factors have increased, those who are concerned about lifestyle-related diseases, those who are often ingesting fat, and are also trying to maintain their health on a daily basis. and for a healthy person it is, is the best preparation, cosmetics, as a food and food additives. Therefore, it is extremely effective in preventing or delaying diseases such as malignant neoplasms by using it as a medicine, functional food, food additive or cosmetic.
[Brief description of the drawings]
FIG. 1 is a drawing comparing the survival rates of normal skin fibroblasts and epidermoid carcinoma cells to which the extract of the present invention was added.

Claims (1)

Anti-skin cancer agent containing an extract obtained by extracting cublet with water-containing monohydric alcohol

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