JPH06298660A - Preventive and therapeutic medicine for cancer produced from rice - Google Patents

Abstract

PURPOSE:To provide a safe and low-cost preventive and therapeutic medicine for cancer, produced from rice and entirely safe even by habitual use. CONSTITUTION:There is provided a preventive and therapeutic medicine for cancer, composed of (1) a ground material of germinated rice, (2) an extract of rice or germinated rice, (3) a material prepared by adding water to rice or germinated rice and enzymatically decomposing it or making a molt act on it, (4) a material prepared by applying an enzymatic decomposition treatment or a malt treatment after, before or during extraction of rice or germinated rice or (5) a material prepared by extracting rice or germinated rice or applying an enzymatic decomposition treatment or a malt treatment thereto and carrying out alcohol fermentation or organic acid fermentation without any more modification or containing it.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a preventive / therapeutic agent for cancer, which can be obtained from rice or sprouted rice as a raw material and can be used in the fields of medicine, food and the like.

[0002]

2. Description of the Related Art Currently, cancer is the most common cause of death in Japanese. Various drugs have been developed to prevent and treat this cancer. However, these drugs have problems of side effects due to administration and restrictions on the amount used and the period of use. In addition, since these are mostly due to the mixture of the single substances, there is a problem from the side effect of the single substance and also from the viewpoint of the safety caused by long-term administration. In other words, the present situation is that a preventive / therapeutic agent for cancer that is effective for preventing / treating cancer, has no side effects, and is safe has not yet been developed.

On the other hand, rice has been used as a staple food, as well as sake, shochu, mirin, vinegar, koji, etc., and has long been indispensable for daily life. In addition to this, bran bags are known for cosmetic purposes. It is believed that these were due to the fact that rice was viewed as merely a staple food, or at best as a source of starch. Also, even if the bran bag is said to be good for the skin, it has been customarily used as it is, and there was no concept of an active ingredient, nor was there any idea of utilizing that active ingredient.

[0004]

At present, side effects of drugs on the human body have become a problem, and there is a need for a cancer preventive / therapeutic agent that has no side effects and is sufficiently safe even if it is commonly used as a preventive / therapeutic agent. Has been done. It is an object of the present invention to provide a preventive / therapeutic agent for cancer from rice, which is safe, inexpensive, and completely safe even when used regularly.

[0005]

[Means for Solving the Problems] From the viewpoint of animal and plant harmony, the present inventors have conducted research on various plant components centering on rice, which is a staple food. In the process, it has become clear that rice has a number of potential and benefits that were previously unpredictable. Therefore, we picked up rice, which is used as a staple food and proved to have the highest safety, as the theme,
I have conducted comprehensive utilization research on rice. As one of the themes, we have conducted intensive studies on cancer preventive and therapeutic agents from rice.In the process, rice and germinated rice contain ingredients that have preventive and therapeutic effects on cancer. Therefore, the present invention has been completed.

[0006] In the present invention, the components contained in rice and germinated rice, which have a cancer-preventing / treating effect, have not yet been elucidated, but rice and germinated rice are treated as follows. Was found to have preventive and therapeutic effects on cancer. Sprouted crushed rice as it is or containing it. Rice or germinated rice extract as it is or containing it. Enzyme-decomposed or hydrolyzed rice hydrolyzed as it is, or containing it. When extracting rice or sprouted rice, the one that has been subjected to enzymatic decomposition or koji before or at the same time as or after the extraction is used as it is or containing it. An extract of rice or germinated rice or a product of enzymatic decomposition or koji which has been subjected to alcohol fermentation or organic acid fermentation as it is or containing it.

The rice used in the present invention is Japonica,
Regardless of indica rice, it refers to brown rice and white rice such as non-glutinous rice and sticky rice, regardless of variety and type. Further, 92% or more of red rice bran or 92% or less of white rice bran, which appears during whitening, may be used, which is inexpensive and economical. Also, germinated rice is used. In addition, since the active ingredient is stable to heat and light, the above raw materials are dipping, steaming, roasting (all sand roasting, net roasting, hot air roasting, etc.),
The raw material treatment such as steam roasting, surface modification such as freeze-drying, photo-modification such as UV irradiation, pressure roasting such as Patrice, and frying may be performed, and the effect was not changed. Although rice and germinated rice are effective as they are, they are preferably crushed and used from the viewpoint of practical use. In order to pulverize the rice and the sprouted rice into powder, it may be carried out by a general method using a pulverizer or a rice mill.

In the case of germinating rice, germinated rice is soaked in water or sprayed with water to germinate. The temperature for germination is 5 to 70 ° C. However, as long as it germinates,
Temperature and time do not matter. Further, when there is a risk of water spoiling during germination, it is preferable to replace the water so that it does not spoil, or to perform some kind of preservative. Here, germination refers to everything from just before germination to germinated ones.
The germinated rice is washed well before use. At this time, it may be dried before use. When extracting rice or sprouted rice, or subjecting it to enzymatic decomposition or koji, the raw material rice is pulverized into granules or powders, and the surface area increases, resulting in higher efficiency. Although it is not necessary to grind, in this case, it takes a long time to decompose and extract the rice tissue.

When water or sprouted rice is extracted with water,
High extraction temperature is efficient, but extraction can be sufficiently performed even at low temperature. However, in the case of a low temperature of 40 ° C. or lower, it is desirable to make PH acidic or alkaline, or add a preservative or alcohol to treat the rice so that it does not spoil. The extraction time may be long or short as long as the active ingredient can be extracted, and may be determined depending on the extraction temperature. The extraction may be carried out under pressure, at normal pressure, or under reduced pressure.

In the case of water extraction, the most problematic is the gelatinization phenomenon. If it becomes pasty, not only the extraction efficiency will deteriorate, but it will be extremely difficult in actual work. In order to prevent this, the reaction may be carried out by adding amylase or acidification may be carried out with hydrochloric acid or the like to cut the starch. By using this method, it can be sufficiently solved and there is no problem in practice.
Since the active ingredient in the extract is stable to acid and alkali, acid decomposition extraction or alkali decomposition extraction is also effective. In this case, neutralization and desalting are performed if necessary.

Also when extracting with an organic solvent, it is desirable to pulverize or pulverize rice as much as possible before extracting. The organic solvent may be a general organic solvent such as alcohol, acetone, n-hexane and methanol, but those harmful to the human body are preferably safe because it is necessary to completely remove the solvent after extraction. When enzymatically decomposing rice or sprouted rice, first add water to the rice or sprouted rice, then
Add enzyme. The amount of water added is appropriately selected depending on the yield, workability, purpose of final use, and the like. Alternatively, the optimum hydration temperature is the optimum temperature of the enzyme or koji, but enzymatic decomposition is sufficiently carried out at a low temperature for a long time. However, if the temperature is lower than 40 ° C., some kind of preservative is required. The temperature may be high as long as it is decomposed. The decomposition time depends on the temperature and the like, but may be short or long as long as the decomposition is performed.

The enzyme used here is one or more of starch degrading enzyme, proteolytic enzyme, lipolytic enzyme, fiber degrading enzyme, lignin degrading enzyme and pectin degrading enzyme. When koji is used, the amount of water added, the temperature of action and the time of action are the same as in the case of enzymatic decomposition. The koji used may be generally used koji, regardless of the type and variety of koji mold. Furthermore, in carrying out the above-mentioned extraction, the above-mentioned enzymatic decomposition and koji may be allowed to act before, simultaneously with or after the extraction. Here, when enzymatic decomposition or koji is allowed to act simultaneously with extraction, specifically, enzymatic decomposition or koji is allowed to act in an organic solvent, or enzymatic decomposition or koji is allowed to act under reduced pressure extraction.

In the present invention, alcohol fermentation or lactic acid fermentation is carried out at the same time as or after each of the above treatments,
It is more effective if organic acid fermentation such as acetic acid fermentation is performed. When carrying out this alcoholic fermentation, the extract obtained as described above, the enzymatic decomposition product (including those obtained by combining enzymatic decomposition and extraction) or the one obtained by allowing koji to act as it is, or after pressing and filtering The obtained liquid is subjected to alcohol fermentation. In addition, enzymatic decomposition and alcohol fermentation may be performed simultaneously. That is, an enzyme or koji, and then sake mother or yeast are added to rice or germinated rice water to perform saccharification and alcohol fermentation. If necessary, alcohol may be fermented by supplementing sugar. In the case of large-scale production, it is desirable to add rice or sprouted rice in three stages or in several stages according to sake brewing, considering the balance between saccharification and fermentation. Especially when treating a small amount, it is effective to add them all at once. If you are worried about spoilage during saccharification and alcohol fermentation,
Add acid or apply appropriate preservatives that do not interfere with fermentation.

[0014] Alcohol fermentation has advantages such as elimination of stickiness, easy concentration, and easy concentration of the active ingredient. When carrying out lactic acid fermentation, it is similar to the case of alcoholic fermentation. In this case, lactic acid bacteria are added instead of liquor or yeast to carry out lactic acid fermentation. Lactic acid fermentation is carried out by a general ordinary method, and the type of lactic acid bacterium and the conditions for lactic acid fermentation do not matter. Next, in the case of acetic acid fermentation, the fermented product obtained as described above is used as it is, or after being diluted to 4-5% of alcohol, acetic acid bacteria are added to perform acetic acid fermentation. For alcohol-free products, acetic acid may be issued by adding alcohol. Acetic acid fermentation is carried out by a general ordinary method, and the type of acetic acid bacterium and the conditions of acetic acid fermentation are not limited.

The product of the present invention obtained as described above is used as it is without separating the residue, or after being pressed and filtered. When used as it is, it is sterilized or sterilized to obtain a product. Alternatively, the product may be dried by freeze-drying or spray-drying to be commercialized. The method of experiment and the result of the experiment for examining the anticancer activity of the product of the present invention are described below.

(Experimental method 1) F344 8 with 5 animals per group
After placing a week-old male rat (average weight 180 g) in an individual gauge and fasting from the morning, water was added to the control in the evening.
For the test, 1 ml of the product of the present invention was administered by a gastric tube. Thirty
Minutes later, as a secondary administration, water was administered as a control, and 2.3 M saline was administered to the positive control and test groups.
As the food, 1 Pellet diet was administered. After 17 hours, the gastric mucosa (pyloric mucosa) was taken out and cultured in an organ to measure complex DNA synthesis. Measurement is carried out in the culture medium [ ³
[H] thymidine was added, and after culturing for 2 hours, DNA synthesis was extracted from the tissue, and [ ³ H] thymi incorporated into DNA was analyzed by a liquid scintillation counter.
Dine was quantified. The results are shown in Table 1.

[0017]

[Table 1]

As shown in Table 1, the amount of [ ³ H] thymidine per μg of replicated DNA synthesized was 430 ± 175 in the control, whereas it was 3960 ± 1683 in the positive control, which was about 10 times. In all the groups to which the product of the present invention was administered, the synthesis of replicated DNA was suppressed. It was found that the effect was improved by combining the extraction and the one treated with enzymatic decomposition or koji, and it was also found to be excellent when alcohol fermentation or organic acid fermentation was performed. Further, as shown in the case of Example 4, white rice showed a stronger effect than brown rice, and red rice bran showed no effect. Therefore, the reason why brown rice is less effective than white rice is because brown rice contains sugar, which is considered to have an effect. Salt is considered to be a promoter of gastric carcinogenesis, and the product of the present invention obviously suppresses its action. This clearly shows that it is effective as an anticancer agent.

(Experimental method 2) F344 4 in 5 animals per group
N-methyl-, a carcinogen, was added to week-old male rats.
N'-nitro-N-nitrosoguanich
ine (MNNG) 150mg / kg per animal per day
After the body weight was drunk for 8 weeks to cause carcinogenesis, the product of the present invention was drunk for 50 weeks instead of drinking water. After 50 weeks, the gastric pyloric gland mucosa was taken out and cultured in an organ to measure complex DNA synthesis. The measurement method is the same as that in Experimental method 1,
[ ³ H] thymidine incorporated in NA was quantified, and the results are shown in Table 2.

The control was given water as normal food and drinking water, and the positive control was given water as MNNG feed and drinking water. In addition, in order to confirm the carcinogenicity of MNNG, control and positive control were carried out in groups of 5 animals each at 8 weeks [ ³ H] thymi.
The dine was measured.

[0021]

[Table 2] (Note) In Example 1, the food of the present invention was mixed and administered.

It is widely known that MNNG is a substance that damages normal genes and causes carcinogenesis in the stomach of rats. By giving 150 mg / kg of body weight daily for 8 weeks, the rat becomes carcinogenic and the gene abnormally proliferates. If the abnormal growth of this gene continues, the oncogene also grows and 10
^{About 6} cells are expressed as cancer cells. As can be seen from Table 2, this is the control 452 ± 143 at the 8th week.
, MNNG administration positive control (8
Week 21) is 4921 ± 1625, which is evident from the significant increase in complex DNA synthesis upon administration of MNNG. However, when the product of the present invention was administered, the increased complex DNA synthesis was apparently reduced in all the products of the present invention, which indicates that the product of the present invention is an excellent anticancer drug that suppresses abnormally proliferated genes. It was found to have an effect.

[0023]

【Example】

(Example 1) 1 kg of rice without germ was soaked in water at 25 ° C for 3 days to germinate rice. After thoroughly washing the germinated rice, it is dried at 50 ° C. for 24 hours, and then,
The product was finely pulverized to obtain 990 g of the product of the present invention. (Example 2) Pulverized rice is crushed to obtain a pulverized product of white rice 500
g was obtained. 1500 ml of water was added to this pulverized product, PH was dropped with hydrochloric acid, and the mixture was left for 10 days. Then, it was squeezed with a squeezing machine to neutralize the resulting clear liquid to obtain 1200 ml of the product of the present invention and 760 g of a residue.

Example 3 Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 3 was carried out to obtain another 1190 ml of the product of the present invention. (Example 4) Pulverized rice is crushed to obtain a pulverized product of white rice 500
g was obtained. Liquefaction enzyme 10g and water 1500m to this crushed material
1 was added. Then, the temperature was gradually raised, and the mixture was boiled and extracted for 5 minutes and then cooled. After that, squeeze with a wringer,
1420 ml of the product of the present invention and 560 g of a residue were obtained.

Example 5 Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 4 was carried out to obtain another 1400 ml of the product of the present invention. (Example 6) Pulverized rice is crushed to obtain 500 pieces of crushed white rice.
g was obtained. 1500 ml of 2N-NaOH was added to this pulverized product and the mixture was left for 5 days. Then, it was squeezed with a squeezing machine to obtain 1350 ml of the clear liquid and 650 g of the residue. 1 of this clarified liquid
Neutralization with 0N-HCl gave 1480 ml of the product of the present invention.

(Example 7) Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 6 was carried out to obtain another 1490 ml of the product of the present invention. (Example 8) Pulverized rice was crushed to obtain 500 pulverized products of white rice.
g was obtained. 1500 ml of 95% ethanol is added to this pulverized product.
Was added and left for 5 days. Then, it was squeezed with a squeezing machine to obtain 1300 ml of the clear liquid and 650 g of the residue. 2000 ml of water was added to this clarified liquid and concentrated by a rotary evaporator to obtain 1500 ml of the product of the present invention.

Example 9 Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 8 was carried out to obtain another 1500 ml of the product of the present invention. (Example 10) Crushed white rice into a crusher, and crushed white rice 50
0 g was obtained. 300 g of koji and 1500 ml of water
Was added and the mixture was allowed to stand at 55 ° C. for 20 hours. Then, it was squeezed with a squeezing machine to obtain 1230 ml of the product of the present invention and 1000 g of a residue.

Example 11 Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 10 was carried out,
1210 ml of another product of the present invention was obtained. (Example 12) Crushed white rice into a crusher, and crushed white rice 50
0 g was obtained. 2 g of protease and 150 water
0 ml was added and the mixture was left at 50 ° C. for 20 hours. Then, the product was squeezed with a squeezing machine to obtain 1310 ml of the product of the present invention and 670 g of a residue.

Example 13 Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 12 was carried out,
Another 1380 ml of the product of the present invention was obtained. (Example 14) Pulverized rice was crushed to obtain a pulverized product of white rice 50
0 g was obtained. 2 g of lipolytic enzyme and 150 water
0 ml was added and the mixture was left at 50 ° C. for 20 hours. Then, it was squeezed with a squeezing machine to obtain 1290 ml of the product of the present invention and 680 g of a residue.

(Example 15) The same operation as in Example 14 was carried out using 500 g of the product of the present invention obtained in Example 1,
Another 1360 ml of the product of the present invention was obtained. (Example 16) Pulverized rice is crushed to obtain a pulverized product of white rice 50
0 g was obtained. 2 g of fiber-degrading enzyme and 150 water
0 ml was added and the mixture was left at 50 ° C. for 20 hours. Then, the product was squeezed with a squeezing machine to obtain 1330 ml of the product of the present invention and 650 g of a residue.

Example 17 Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 16 was carried out,
Another 1370 ml of the product of the present invention was obtained. (Example 18) Pulverized rice was crushed to obtain 50 crushed pieces of white rice.
0 g was obtained. 2g starch degrading enzyme and 150g water
0 ml was added and the mixture was left at 55 ° C. for 20 hours. Then, it was squeezed with a squeezing machine to obtain 1380 ml of the product of the present invention and 600 g of a residue.

(Example 19) Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 18 was carried out,
Another 1400 ml of the product of the present invention was obtained. (Example 20) White rice was crushed to obtain 50 pieces of crushed white rice.
0 g was obtained. Add 2 g of pectin-degrading enzyme and 1 part of water to this ground product.
500 ml was added and left at 50 ° C. for 20 hours. After that, squeezing with a squeezing machine, 1320 ml of the present invention product and residue 660
g was obtained.

(Example 21) The same operation as in Example 20 was carried out using 500 g of the product of the present invention obtained in Example 1,
Another 1300 ml of the product of the present invention was obtained. (Example 22) Crushed white rice into a crusher, and crushed white rice 50
0 g was obtained. To this pulverized product, 2 g of proteolytic enzyme, 2 g of lipolytic enzyme, 2 g of fiber degrading enzyme, 2 g of starch degrading enzyme, 2 g of pectin degrading enzyme and 1500 ml of water were added, and the mixture was heated at 50 ° C. for 2 hours.
It was left for 0 hours. After that, the product of the present invention 14
20 ml and 560 g of residue were obtained.

(Example 23) The same operation as in Example 22 was carried out using 500 g of the product of the present invention obtained in Example 1,
Another 1440 ml of the product of the present invention was obtained. (Example 24) The same operation as in Example 22 was carried out to obtain 2000 g of an enzymatic decomposition product of white rice. Then, the temperature was gradually raised, and the mixture was boiled and extracted for 5 minutes and then cooled. Then, it was squeezed with a squeezing machine to obtain 1400 ml of the product of the present invention and 550 g of a residue.

Example 25 Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 24 was carried out,
1420 ml of another product of the present invention was obtained. (Example 26) Pulverized rice was crushed to obtain a pulverized product of white rice 50
0 g was obtained. To this crushed product, 300 g of koji and 1500 ml of 40% ethanol were added, and the mixture was left at 55 ° C. for 48 hours. After that, squeeze with a squeezing machine and clarified liquid 1300 ml and residue 850
g was obtained. Then, 1000 ml of water was added to the clarified solution and concentrated with a rotary evaporator to obtain the product of the present invention 13
00 ml was obtained.

Example 27 Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 26 was carried out,
Another 1300 ml of the product of the present invention was obtained. (Example 28) White rice extract 2 was prepared in the same manner as in Example 4.
000 g was obtained. To this extract, 2 g of proteolytic enzyme, 2 g of lipolytic enzyme, 2 g of fiber degrading enzyme, 2 g of starch degrading enzyme,
2 g of pectin degrading enzyme was added, and the mixture was left at 50 ° C. for 24 hours. Then, it was squeezed with a squeezing machine to obtain 1400 ml of the product of the present invention and 580 g of a residue.

(Example 29) Using 500 g of the product of the present invention obtained in Example 1, the same operation as in Example 28 was carried out,
Another 1390 ml of the product of the present invention was obtained. (Example 30) In the same manner as in Example 24, 2000 g of an enzyme-decomposed extract of white rice was obtained. Yeast was added to this enzyme-decomposed extract, and alcoholic fermentation was carried out for 16 days. Then, it was squeezed with a squeezing machine to obtain 1880 ml of the product of the present invention and 80 g of a residue.

(Example 31) The same operation as in Example 30 was carried out using 500 g of the product of the present invention obtained in Example 1,
Another 1800 ml of the product of the present invention was obtained. (Example 32) In the same manner as in Example 24, 2000 g of an enzyme-decomposed extract of white rice was obtained. The enzyme-decomposed extract was sterilized by boiling, cooled to 37 ° C., 200 ml of a starter in which lactic acid bacteria had been previously cultured was added, and the mixture was well stirred and sealed, and lactic acid fermentation was carried out at 37 ° C. for 2 days. Then, it was squeezed with a squeezing machine to obtain 1380 ml of the product of the present invention and 590 g of a residue.

(Example 33) The same operation as in Example 32 was carried out using 500 g of the product of the present invention obtained in Example 1,
Another 1400 ml of the product of the present invention was obtained. (Example 34) The product 1000 of the present invention obtained in Example 24.
80 ml of 95% ethanol was added to ml, and acetic acid fermentation was performed for 20 days. Then, it is filtered and the product of the present invention 990 m
1 was obtained.

Example 35 The same operation as in Example 34 was carried out using 500 g of the product of the present invention obtained in Example 1,
Another 1000 ml of the product of the present invention was obtained. Examples of blending the product of the present invention into a tablet and a soft drink will be described below. The formulation examples are not limited to the examples below.

(Example 36) Tablet 100 g of the product of the present invention obtained in Example 24 was dried by freeze drying to obtain 20 g of a dried product. This dried product 1
Tablets were obtained from 0 g as described below. Product of the present invention 10 g Polyethylene glycol 6000 10 g Sodium lauryl sulfate 1.5 g Corn starch 3 g Lactose 25 g Magnesium stearate 0.5 g Polyethylene glycol 600 after weighing the above components
0 is heated to 70 to 80 ° C., the product of the present invention, sodium lauryl sulfate, corn starch and lactose are added thereto, mixed and then cooled as it is. The solidified mixture is crushed by a grinder. The granules are mixed with magnesium stearate and compressed to give tablets having a weight of 250 mg.

(Example 37) Soft drink The product of the present invention obtained in Example 22 15% (weight ratio) Licorice extract 0.01% Sugar 4% Lemon juice 2.5% Purified water 78.49% By a conventional method After mixing and stirring, soft drink was obtained.

[0043]

INDUSTRIAL APPLICABILITY According to the present invention, by continuously eating and drinking, an excellent cancer prophylactic / therapeutic agent which is simple, completely safe, and has a cancer prevention / treatment effect can be obtained. Since rice has been the staple food until now, little has been developed about its manufacturing method and use in new fields other than food. Furthermore, rice has been the staple food until now, and its safety has been well demonstrated. That is, the present invention has not only found a very excellent cancer preventive / therapeutic agent, but has also found a new application, which is said to be overproduction of rice.
It is extremely meaningful that we can increase consumption by improving the image of rice and rice.

Claims (5)

[Claims] 1. A prophylactic / therapeutic agent for cancer, which comprises a crushed product of sprouted rice as it is or contains it. 2. A preventive / therapeutic agent for cancer comprising rice or an extract of germinated rice as it is or containing the same. 3. A preventive / therapeutic agent for cancer, which is obtained by enzymatically decomposing or hydrolyzing germinated rice hydrolyzate, or containing it. 4. A method for preventing or treating cancer, which comprises the step of extracting rice or sprouted rice with enzymatic decomposition or koji before or after extraction, simultaneously with or after extraction, or containing the same. Agent. 5. Prevention and treatment of cancer comprising rice or germinated rice extract or enzyme-decomposed or koji-acted one which has been subjected to alcohol fermentation or organic acid fermentation as it is or containing the same. Agent.