JP2006306855A - Oil and fat-containing composition for suppressing carcinogenesis - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an agent for suppressing carcinogenesis effective for prevention of hereditary cancer or occupational cancer, or for prevention or the like of relapse after treatment of the cancer; and to obtain a food and drink having a function for suppressing the carcinogenesis. <P>SOLUTION: The oil and fat-containing composition containing an oil and fat in which hydrophobic extract of licorice is dissolved has activities for suppressing the carcinogenesis. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a fat-containing composition for inhibiting carcinogenesis, which can be used in foods and drinks such as health foods and health functional foods (special health foods, nutritional functional foods), pharmaceuticals, quasi drugs, cosmetics, and the like. .

  Various studies have been conducted on cancer therapy. In particular, with regard to therapeutic agents, many researches and developments have been conducted, and some drugs are actually used in the medical field. However, there are still no specific drugs that cure cancer, and currently used anti-cancer drugs such as anti-cancer drugs or immunotherapeutic drugs have problems of weak therapeutic effects and strong side effects. The problems with such drugs after cancer development are the difficulty of allowing the drug to act specifically on cancer cells without affecting normal cells, and the inherent safety of drugs that are chemically synthesized substances. Due to sex problems.

  Recently, apart from therapeutic agents after the onset of cancer, the search for a carcinogenic inhibitor is particularly emphasized from the viewpoint of suppressing the occurrence of cancer. If it is possible to extract or synthesize effective carcinogenic substances and use them as drugs to suppress carcinogenesis, it is possible to prevent hereditary cancer or occupational cancer. Such drugs are considered to greatly contribute to future new medical care and health maintenance in daily life. It is preferable that such a carcinogenic inhibitor can be easily taken in daily life. Furthermore, it is a necessary condition that it is effective even by oral administration and has no side effects. However, so far, there is no example of using a specific carcinogenic inhibitor having no safety problem as a drug for preventing or treating carcinogenesis.

  Licorice is a plant belonging to the genus Glycyrrhiza, which is used for food and medicine (herbal medicine). The main varieties are Glycyrrhiza. Glabra, G. G. uralensis, G. Examples include inflators (G. inflata). All varieties contain glycyrrhizin (glycyrrhizic acid) which is a hydrophilic component, but flavonoids of hydrophobic components contain specific compounds depending on the cultivar. This variety-specific flavonoid may be used for licorice variety identification.

  Among the extracts obtained from licorice, a licorice hydrophobic extract containing a large amount of licorice flavonoids and having a very small amount of glycyrrhizin was found to be useful for the prevention and / or treatment of multiple risk factor syndrome. (See Patent Document 1). Furthermore, in the latest research, it has been found that this licorice hydrophobic extract has PPARγ ligand activity, and its active ingredient is a flavonoid (see Patent Document 2). Among them, G. PPARγ ligands with high flavonoids, glabrene, glabrizine, glabrol, 3′-hydroxy-4′-O-methyl glabridine, 4′-O-methyl glabrizine and Hispa glabridine B, which are characteristic flavonoids contained in the extract of grabra It has been found to have activity (see Patent Document 2).

On the other hand, compounds contained in the licorice hydrophobic extract, such as licorice hydrophobic flavonoids, hardly dissolve in water, and are easy to consolidate in the organic solvent extract, and the color progresses rapidly. Because of its remarkable nature, it is difficult to use. In order to solve this problem, it has been proposed to dissolve in medium-chain fatty acid triglycerides and stabilize the preparation (see Patent Document 3). Patent Document 3 suggests that the licorice hydrophobic flavonoid preparation can be used as an antioxidant, antibacterial agent, enzyme inhibitor, coloring agent, antitumor agent, antiallergic agent, and antiviral agent. It has not been tested and it is unclear whether it can be used for these applications in practice. Furthermore, in this document, detailed examination of the type and use of the extraction solvent for obtaining the licorice hydrophobic extract is not made.
International Publication No. 02/047699 Pamphlet International Publication No. 03/037316 Pamphlet Japanese Patent No. 2794433

  The subject of this invention is providing the oil-and-fat containing composition for carcinogenesis suppression.

Surprisingly, the present inventors have found that a solution obtained by bringing an alcohol extract obtained by contacting licorice with alcohol into a fat-containing composition has a carcinogenesis-inhibiting action. Thus, the object of the present invention has been achieved. Therefore, the present invention provides the following.
(1) A fat and oil-containing composition for inhibiting carcinogenesis, comprising a solution obtained by bringing a licorice hydrophobic extract into contact with fats and oils.
(2) The composition according to the above (1) 1, which is an amount capable of ingesting 0.45 to 3.6 mg / kg body weight per day as an adult licorice hydrophobic extract.
(3) The composition according to (1) above, wherein the fat or oil comprises a glycerin fatty acid ester containing a medium chain fatty acid triglyceride and / or a fatty acid partial glyceride.
(4) The composition according to (1) above, wherein the fat or oil contains a glycerin fatty acid ester containing 50% by weight or more of medium chain fatty acid triglyceride.
(5) The composition according to (4) above, wherein the fat / oil comprises a glycerin fatty acid ester containing 50% by weight or more of a fatty acid partial glyceride.
(6) The composition according to any one of (1) to (5), wherein the composition is for food and drink.
(7) The composition according to any one of (1) to (5), which is used for medicine.
(8) A method for producing a composition for preventing carcinogenesis and / or treating cancer, which comprises contacting a hydrophobic extract of licorice with fats and oils.
(9) A method for preventing carcinogenesis, comprising administering, as an active ingredient, a solution obtained by bringing a hydrophobic extract of licorice into contact with fats and oils.

  ADVANTAGE OF THE INVENTION According to this invention, the fats and oils for cancer prevention or treatment which can be utilized for food / beverage products, such as health food and health functional food (special health food, nutrition functional food), or a medicine, a quasi drug, cosmetics, etc. A containing composition is provided.

Hereinafter, embodiments of the present invention will be described in detail.
In one embodiment, the present invention provides a fat-containing composition for preventing or treating cancer, comprising a solution obtained by contacting a licorice hydrophobic extract extracted from licorice with an organic solvent with fats and oils.

The fat and oil-containing composition described here is a composition in which the licorice hydrophobic extract is dissolved in the fat and oil, a composition in which insoluble impurities are removed from the fat and oil in which the licorice hydrophobic extract is dissolved, and a composition in which the fat and oil are further added. Or a composition obtained by removing the hydrophobic extraction solvent from the composition, and is a composition for eating and drinking, for medicine, for quasi-drugs, etc., containing these compositions. That is, a composition obtained by dissolving a licorice hydrophobic extract in fats and oils, a composition obtained by mixing this with other ingredients, and a composition obtained by processing this composition for food and drink, for pharmaceutical use, for external use in pharmaceuticals, etc. Any of these are included in the oil-containing composition of the present invention.
The amount of the licorice hydrophobic extract in the oil-containing composition is not particularly limited, but from the viewpoint of solubility in fats and oils, the upper limit is preferably 30% by weight or less in terms of the amount not containing the hydrophobic extraction solvent, From the viewpoint of the effectiveness of the licorice hydrophobic extract, the lower limit is preferably 0.01% by weight or more. More preferably, it is 0.1-30 weight% in an oil-containing composition, More preferably, it is 1-10 weight%.

 The licorice material used in the present invention is not limited as long as it is a plant belonging to the genus Glycyrrhiza, Glycyrrhiza. Glabra, G. G. uralensis, G. Examples include inflators (G. inflata). Among these, from the viewpoint of safety, G. has the widest distribution and rich food experience. Grubra licorice is preferred.

  In the present invention, a method for obtaining a licorice hydrophobic extract is not particularly limited. It can be obtained from Grubra licorice. When the extract is obtained from licorice, its method is not particularly limited, but it can be obtained by extraction with an organic solvent such as alcohol, ethyl acetate, acetone, etc. Extraction with alcohol, especially ethanol, is preferred. Ethanol is not particularly limited as long as it is used in the production of foods and pharmaceuticals, but its water content is 30% or less, preferably 10% or less, more preferably 5%, for the purpose of extracting hydrophobic components. It is as follows.

 The weight ratio of the alcohol to the licorice material is not particularly limited, but is preferably 0.5: 1 to 20: 1, more preferably 1: 1 to 10: 1 from the viewpoint of extraction efficiency. Further, the extraction temperature and the extraction time are not particularly limited, but in order to increase the extraction rate, the extraction time is 1 hour or more, preferably 20 ° C. or higher, preferably 20 to 80 ° C., more preferably 30 to 60 ° C. Is preferably performed for 1 to 10 hours, more preferably 1 to 3 hours. Furthermore, it is possible to efficiently extract the hydrophobic component from the licorice material by performing the extraction a plurality of times, and it is preferable to extract at least twice.

 The extract obtained in this way may be used as it is, but it is further purified or purified by column treatment, deodorization treatment, decolorization treatment, etc., and further using a solid from which the solvent has been removed. Also good. The extract can be a purified one, but can also be a crudely purified product as long as it does not contain any unsuitable impurities as foods, drinks, pharmaceuticals, quasi drugs, and the like.

  The fats and oils used in the present invention are glycerin fatty acid esters containing medium chain fatty acid triglycerides, preferably glycerin fatty acid esters containing about 50% by weight or more of medium chain fatty acid triglycerides, more preferably about 70% by weight of medium chain fatty acid triglycerides. % Glycerol fatty acid ester. Here, the medium-chain fatty acid triglyceride includes a fatty acid having about 6 to 12 carbon atoms as a constituent fatty acid, and the constituent ratio of the fatty acid is not particularly limited, but the constituent ratio of the fatty acid having about 8 to 10 carbon atoms is about 50 wt. % Or more is preferable, and about 70% by weight or more is more preferable. In particular, a medium-chain fatty acid triglyceride having a specific gravity of about 0.94 to 0.96 at about 20 ° C. and a viscosity of about 23 to 28 cP at about 20 ° C. is more preferable. Moreover, as the medium chain fatty acid triglyceride, any of naturally derived ones and those prepared by transesterification can be used.

  The fat used in the present invention is a glycerin fatty acid ester containing a fatty acid partial glyceride, preferably a glycerin fatty acid ester containing a partial glyceride of about 50% by weight or more, more preferably a partial glyceride of about 70% by weight or more. Glycerin fatty acid ester. The partial glycerides here are diglycerides (1,2-diacylglycerol, 1,3-diacylglycerol) or monoglycerides (1-monoacylglycerol, 2-monoacylglycerol), and any of them may be used. A mixture of the two may be used, and the constituent fatty acids are not particularly limited, but diglycerides composed of unsaturated fatty acids and / or medium chain fatty acids are preferred from the viewpoint of processability. In addition, as the partial glyceride, any of those derived from nature, those prepared by transesterification, and the like can be used. Furthermore, the fats and oils used in the present invention may be a mixture of the above-mentioned medium chain fatty acid triglycerides and partial glycerides.

  In the present invention, the method for obtaining the oil / fat-containing composition is not particularly limited, but it can be obtained by dissolving the licorice hydrophobic extract in oil / fat. In this case, it can be carried out by ordinary operations such as stirring or mixing, but after the extract is dissolved in fats and oils by operations such as stirring or mixing, impurities that are insoluble in fats and oils are removed by operations such as filtration or centrifugation. Is desirable. Alternatively, the method described in WO 03/84556 is suitable. For example, although it is possible to extract directly from licorice raw material with fats and oils, it can be obtained by removing ethanol after mixing an organic solvent containing a licorice hydrophobic extract, preferably an ethanol solution and fats and oils. Furthermore, in this invention, you may add fats and oils with respect to the mixture of these licorice hydrophobic extracts and fats and oils, and may adjust the composition ratio of a licorice hydrophobic extract and fats and oils.

  Generally, a licorice hydrophobic extract is unstable in a powder state, and its stability is not improved even when dissolved in an organic solvent such as ethanol. However, the stability can be improved by dissolving the extract in the oil used in the present invention. Moreover, since this extract is sparingly water-soluble, it can also be expected that its absorbability is improved by dissolving it in the oil used in the present invention.

The composition of this invention may contain the carrier accept | permitted for eating and drinking, a medicine, or cosmetics. The pharmaceutical carrier can be any inert, organic or inorganic material suitable for oral, enteral, transdermal, subcutaneous, or parenteral administration, including but not limited to water, gelatin, gum arabic, lactose Microcrystalline cellulose, starch, sodium starch glycolate, calcium hydrogen phosphate, magnesium stearate, talc, and colloidal silicon dioxide, and the like. Such compositions can also contain other pharmacologically active agents, and conventional additives such as stabilizers, wetting agents, emulsifying agents, flavoring agents, and buffering agents, and the like.
The oil or fat-containing composition for preventing or treating cancer according to the present invention is from the group consisting of glabrene, glabrizine, glabrol, 3′-hydroxy-4′-O-methyl glabridine, 4′-O-methyl glabrizine, and hispagrabridine B. It is characterized by containing fats and oils dissolving at least one selected compound.

  In the present invention, grabrene, grabridine, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, and Hispa grabridin B are not particularly limited. It can be obtained from Grubra licorice. When the compound is obtained from licorice, the method is not particularly limited, but the compound is contained in a licorice hydrophobic extract obtained by extraction with an organic solvent such as alcohol, ethyl acetate, and acetone, and the extract is used as it is. However, it is also possible to use those that have been roughly purified or purified by column treatment, deodorization treatment, decolorization treatment or the like.

  Of course, the compound may be any compound derived from natural sources such as plants, chemically synthesized or biosynthesized by cultured cells. Moreover, although the refined | purified thing can be used for this compound, as long as it does not contain an inappropriate impurity as food / beverage products, a pharmaceutical, a quasi-drug, cosmetics, etc., it can also use the roughly refined | purified thing.

  Among these compounds, at least one selected from the group consisting of grabridine and comprising grabrene, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, Hispa grabridin B It is preferable to contain a compound. Furthermore, it contains at least one compound selected from the group consisting of glabrizine and glabrene, and also consisting of glabrol, 3′-hydroxy-4′-O-methyl glabridine, 4′-O-methyl glabridine, and Hispa grab lysine B More preferably. In particular, it is most preferable to contain all of grabrene, grabridine, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, and hispagrabridine B.

Glabridin, 3′-hydroxy-4′-O-methylglabridin, 4′-O-methylglabridin, Hispagrabridine B (Hyspaglabridin B) is a flavonoid classified as isoflavan, and is a compound represented by the following general formula (1).
[Gravidine is R1 = H, R2 = OH, 3′-hydroxy-4′-O-methylgrabridine is R1 = OH, R2 = OCH ₃ , 4′-O-methylgrabridine is R1 = H, R2 = OCH ₃ , In Hispagrabridine B, R1 to R2 are —CH═CH—C (CH ₃ ) ₂ —O— to form a six-membered ring. ]

Glabrene is a flavonoid classified into isoflav-3-ene and is a compound represented by the following general formula (2).

Glabrol is a flavonoid classified as flavanone, and is a compound represented by the following general formula (3).

Grabrene, glabrizine, glabrol, 3′-hydroxy-4′-O-methyl glabrizine, 4′-O-methyl glabrizine, and Hispa glabrizine B are components that are specifically contained in Glycyrrhiza glabra among licorice It is almost not included in other varieties. However, G. It may be included in hybrids of grabra and other varieties. The compound can be detected and quantified separately from other flavonoid components by HPLC analysis using a reverse phase column such as ODS.
If desired, another carrier can be added to the resulting oil / fat extract to produce an oil / fat-containing composition.

  When an extract containing the compound or a crude product of the compound is used, since impurities other than the compound are contained, the compound is dissolved in an oil or fat by an operation such as stirring or mixing, and then filtered or centrifuged. It is desirable to remove impurities insoluble in fats and oils by operations such as these. When a purified product of the compound is used, a uniform solution can be easily obtained. Moreover, when using the extract containing this compound or the crude refined | purified product of this compound, after melt | dissolving in organic solvents, such as ethanol, and mixing the solution and fats and oils, an organic solvent can also be distilled off.

  In the present invention, the method for dissolving grabrene, grabridine, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, and Hispa grabridin B in fats and oils is not particularly limited, It can be carried out by an operation such as stirring or mixing.

  In general, grabrene, grabridine, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, and hispagrabridine B are unstable in a powder state and dissolved in an organic solvent such as ethanol. However, stability is not improved. However, the stability can be improved by dissolving the compound in the oil used in the present invention. The fats and oils are the same as in the previous embodiment.

  The form of the oil-containing composition for preventing or treating cancer according to the present invention is not particularly limited, and is a food or drink such as a health food or a health functional food (a food for specified health use or a nutritional functional food), or a pharmaceutical product or quasi-drug. It can be used for cosmetics and cosmetics. For example, fats and oils dissolving at least one compound selected from the group consisting of grabrene, grabridine, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, and Hispa grabridine B Can be used alone for cooking, soft capsule preparation, lotion and the like. Moreover, since it can be freely mixed with an oily object, it can be mixed with other oils and fats according to the purpose to adjust the physical properties. In this case, it is preferable that the other fats and oils are foods or pharmaceuticals, and the type and use amount thereof are determined in consideration of various conditions such as physical properties and use temperature range required for each product. By adjusting the amount, characteristics such as consistency and melting point can be controlled. For example, vegetable oils such as corn oil, rapeseed oil, Haieru rapeseed oil, soybean oil, olive oil, safflower oil, cottonseed oil, sunflower oil, rice bran oil, palm oil, palm kernel oil, fish oil, beef tallow, pork fat, milk fat, egg yolk oil Animal oils such as these, oils and fats that have been subjected to fractionation, hydrogenation, transesterification, etc. from these as raw materials, or mixed oils thereof can be used.

  The oil-containing composition thus obtained can be used as liquid oils such as salad oil and frying oil, plastic oils such as margarine and shortening, water-in-oil emulsions, and oil-in-water emulsions. In addition, as fat and oil-containing compositions for eating and drinking produced using these as raw materials, confectionery such as chewing gum, chocolate, candy, jelly, biscuits and crackers, frozen confectionery such as ice cream and ice confectionery, milk beverage, soft drink, Beverages such as energy drinks and beauty drinks, noodles such as udon, Chinese noodles, spaghetti, instant noodles, kneaded products such as strawberries, bamboo rings, and half pieces, seasonings such as dressings, mayonnaise, sauces, bread, ham, soup, various retort foods Various frozen foods are exemplified and can be used for pet food and livestock feed.

  Furthermore, for the purpose of fortification, various vitamins such as vitamins A, D, and E may be added and used together. Various salts as flavoring agents, various flavorings, milk-related substances such as whole milk powder, You may add skim milk powder, fermented milk, milk fat, etc., and may use together. Further, as raw materials other than the above, all of the antioxidants, colorants and the like used in ordinary water-in-oil emulsions and oil-in-water emulsions can be used.

  Grabrene, glabrizine, glabrol, 3′-hydroxy-4′-O-methyl glabridine, 4′-O-methyl glabridine, Hispa glabridin B contained in the oil-containing composition for preventing and / or suppressing carcinogenesis according to the present invention In order to exert the effect of preventing and / or suppressing the carcinogenesis, 0.01 to 10 mg / kg body weight, preferably 0.45 to 3.6 mg / kg body weight per adult day is taken as the licorice extract. It is desirable to contain the amount of the compound in the oil-containing composition. The content of the compound was measured by HPLC analysis using a reverse phase column such as ODS.

  The term “carcinogenesis suppression” in the present specification means to suppress the generation of cancer cells and to suppress the growth of cancer cells once generated. The kind of tumor suppressed by the carcinogenesis inhibitor of the present invention is not limited. That is, it does not matter whether it is an epithelial tumor, non-epithelial tumor or even benign or malignant. For example, various organs in the body such as stomach, intestine, lung, liver, kidney, pancreas, gallbladder, uterus, ovary, testis, prostate, or brain, etc. It can be a tumor such as a bone tumor or a lymphoid tumor.

  Examples of administration of the cancer suppressant of the present invention or ingestion as food or drink include prevention of hereditary cancer, prevention of cancer caused by the environment or lifestyle, or recurrence and tumor metastasis after tumor removal surgery Administration is one of prevention or cancer treatment. More specifically, when a person who has a high possibility of developing cancer in the future by genetic diagnosis takes a prophylactic intake of the cancer suppressant of the present invention before onset, exposure to a person with smoking habits or radioactive substances There is a case where a person engaged in the occupation to be taken prophylactically, or a case where it is administered instead of or in parallel with the administration of an anticancer agent as a chemotherapy.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.
<Example 1>

Ethanol extraction (49.25 L, 45 ° C., 2 hours, 2 extractions) from 9.85 kg of Afghan licorice (G. glabra), followed by concentration gave 4.4 L of concentrated solution. 3 L of the solution was further concentrated, and activated carbon treatment and concentration yielded 81.2 g of an ethanol solution containing a licorice hydrophobic extract.
629.2 g of ethanol solution (containing 125.8 g of licorice hydrophobic extract) and Actor M-2 (RIKEN Vitamin Co., Ltd.), a medium chain fatty acid triglyceride (MCT): fatty acid composition is C8: C10 = 99: 1) 187.6 g was mixed and stirred for about 1 hour while being kept at about 80 ° C., and then ethanol was removed by concentration under reduced pressure. Insoluble matter was separated by suction filtration, and 45.7 g of MCT was further added to the filtrate after filtration to obtain 297.0 g of MCT solution. 1 g of the obtained MCT solution was dissolved in methanol for HPLC to make the total amount 100 ml. As a result of performing HPLC analysis under the following conditions using this solution as a sample, 6.6 mg, 30.8 mg, and 12.6 mg of grabrene, grabridine, grabrol, and 4′-O-methylgrabridine per 1 g of MCT solution, 3.7 mg was included.
The licorice extract containing gravuren, glabridine, glabrol, 4′-O-methyl glabridine was about 30% by weight of the MCT solution.

As the HPLC analysis condition analysis column, J'sphere ODS-H80, 4.6 × 250 mm (YMC) was used at a column temperature of 40 ° C. In the mobile phase, the acetonitrile ratio with respect to the 20 mM phosphoric acid aqueous solution is kept constant at 35% from the start of analysis to 20 min, and is increased at a constant ratio so that it becomes 70% after 75 min after 20 min, and 80% from 75 min to 80 min. The flow rate was 1 ml / min under a constant gradient condition. The injection volume was 20 μl, and the detection wavelength was 254 nm. The retention time of each compound was 40.0 min for grabrene, 50.2 min for grabridine, 58.3 min for grabrol, and 66.8 min for 4′-O-methyl grabridine.
<Example 2>

Carcinogenesis Inhibitory Action In order to examine the effect of the MCT solution of Example 1 on carcinogenesis, a search using a medium-term liver carcinogenicity test method (Ito test) was performed. This test method is one of two-stage carcinogenesis models using rodents, and targets the rat liver. 313 or more chemical substances have already been searched using this test method, and this is a highly reliable and useful search method for searching for carcinogens or carcinogens. Therefore, it is recognized as an alternative to the conventional long-term carcinogenicity test at the International Conference on Harmonization of Regulations for Tripolar Drugs between Japan, the US and the EU (ICH). In addition, this study was conducted in accordance with GLP (Good Laboratory Practice) standards based on the “Ministerial Ordinance on the Practice of Nonclinical Studies on Drug Safety” (Ministry Ordinance No. 21 of March 26, 1997). The reliability of the test results is sufficiently high.
Seven groups (groups 1-5: 15 animals, groups 6, 7) so that no statistically significant difference in average body weight was produced from 100 6-week-old male F344 rats by computerized random block method: 9 animals). For initiation treatment for hepatocarcinogenesis, rats were administered intraperitoneally with diethylnitrosamine (DEN) at a dose of 200 mg / kg, and 2 weeks later, MCT solution as a test substance was 0 (control group), Forcible oral administration was carried out once a day at a dose of 150, 300 and 600 mg / kg for 6 weeks at a frequency of 7 times / week (Group 1-4). 150, 300 and 600 mg / kg of the MCT solution used in the test correspond to 45, 90 and 180 mg / kg body weight in terms of licorice extract as an active ingredient. Further, phenobarbital sodium salt (S.PB) was administered as a positive control group at a concentration of 500 ppm (group 5). A DEN-untreated control group and a test substance 600 mg / kg group were also provided (Groups 6 and 7). During the third week of the experiment (one week after the start of test substance administration), partial hepatectomy was performed on all animals to amplify liver lesions. After 8 weeks from the start of the experiment (after the test substance administration period), all the rats were sacrificed and necropsied, and the livers were removed. Three pieces of tissue were cut from each liver and fixed with 10% buffered formalin solution, and then a paraffin block was prepared and sliced to prepare a tissue specimen. For the obtained rat liver tissue specimen, expression of placental glutathione S-transferase (GST-P), which is an index of liver precancerous lesion, was expressed by immunohistochemical staining using the avidin-biotin complex method. Examined. After measuring the area of the liver section and the number and area of GST-P positive cell nests with a diameter of 0.2 mm or more using a pathological specimen image analyzer IPAP-WIN (Sumika Techno Service Co., Ltd.), the liver section 1 cm ² The number and area per hit were calculated for quantitative analysis. In addition, for each of the 3 cases in groups 6 and 7, 1 part was collected from the rest of the liver subjected to immunohistochemical examination, fixed with 4% glutaraldehyde, and then subjected to electron microscopy. Statistical analysis is based on the equal variance test using the Berlett method at 5% significance level for the test of differences in body weight, organ weight, and liver immunohistochemical tests between groups 1 and 2-4. Went. In the case of equal variance, a one-sided test by parametric Dunnett method was performed, and in the case of unequal variance, a one-sided test by nonparametric Steel method was performed. The mean value between the first group (control group) and the fifth group (S.PB group) treated with DEN and between the sixth group (control group) and the seventh group (600 mg / kg group) without DEN treatment. The F-test was used for the difference test. The student t-test (one side) was used for equal variance, and the Welch test (one side) was used for non-equal variance. Tables 1 and 2 show the results of quantitative analysis of liver weight and GST-P positive cell nest.
During the administration period, there was no change in general condition, dead animals, food intake and body weight due to test substance administration. In terms of water intake, the test substance was administered because the DEN-treated 300 and 600 mg / kg groups (Groups 3 and 4) and the DEN-untreated 600 mg / kg group (Group 7) showed a continuous high trend. It was thought that Regarding liver weight, the DEN-treated 300 and 600 mg / kg groups (Groups 3 and 4) showed significant high absolute and relative weights, and the 150 mg / kg group (Group 2) showed significant high relative weights. Admitted. Furthermore, in the 600 mg / kg group (group 7) without DEN treatment, it was considered that the test substance administration had an effect due to the significant increase in absolute and relative weights. There were no histological differences in levels. Furthermore, no changes were observed in the electron microscopic examination of the liver performed in the 600 mg / kg group (group 7) without DEN treatment. Thus, increased liver weight was not considered toxic. In the measurement of the liver GST-P positive cell nest, the number per unit area in the DEN-treated 600 mg / kg group (Group 4) is significantly lower than that in the control group (Group 1), About the area per unit area, the 150 and 600 mg / kg group (2nd and 4th group) showed the significantly low value.
On the other hand, in the measurement of the GST-P positive cell nest of the positive control S.PB group (group 5), both the number and area per unit area were clearly high, demonstrating the validity of this test. In addition, it is known that a compound exhibiting peroxisome proliferative activity in the liver exhibits a false negative or false suppressive action in this test system, but as described above, in the 600 mg / kg group (Group 7) without DEN treatment. In the electron microscopic examination of the liver performed, the possibility of false negative and false suppressive effects in this test result was denied because no peroxisome proliferative activity was observed in hepatocytes.
As described above, the MCT solution was administered by oral gavage at doses of 150, 300 and 600 mg / kg. As a result, the number and area of GST-P positive cell foci were not increased at any dose, but decreased at 600 mg / kg. Was recognized. Therefore, it was revealed that the MCT solution has no carcinogenic action in the rat liver and has a carcinogenic inhibitory action.
It is known that human sensitivity is about 50 to 100 times higher than that of rats. Therefore, the fact that rats have a carcinogenic inhibitory effect at a dose of 150 to 600 mg / kg of MCT solution (that is, 45 to 180 mg / kg in terms of licorice extract which is an active ingredient) means that licorice extract 0. It is estimated to have a carcinogenic inhibitory effect at a dose of 45 to 3.6 mg / kg.
<Example 3>

Production of Soft Capsule The MCT solution of Example 1 was pressed into a gelatin coating using a rotary soft capsule production apparatus to obtain a soft capsule with an internal volume of 350 mg.
<Example 4>

Manufacture of margarine 80 parts by weight of hardened cottonseed oil (trade name: Snowlight, Kaneka Co., Ltd.), 20 parts by weight of the MCT solution of Example 1, 10 parts by weight of unsalted butter (Yotsuba Dairy Co., Ltd.) 0.2 parts by weight of ester (trade name: Emergy MS, Riken Vitamin Co., Ltd.) and 0.2 parts by weight of lecithin were added and dissolved by heating at 60 ° C. to prepare an oil phase.
While stirring, 15.1 parts by weight of water was added to 84.9 parts by weight of the prepared oil phase, emulsified for 20 minutes, and then cooled and kneaded with a combinator to prepare margarine.
<Example 5>

Production of Concentrated Milk After heating 10 parts by weight of the MCT solution of Example 1 to 70 ° C., 0.1 part by weight of lecithin and 0.1 part by weight of polyglycerin fatty acid ester were sequentially dissolved to prepare an oil phase.
An aqueous phase was prepared by dissolving 25 parts by weight of skim milk powder, 0.1 part by weight of glycerin fatty acid ester and 0.1 part by weight of sucrose fatty acid ester in 64.6 parts by weight of water at 60 ° C.
The prepared aqueous phase and oil phase were pre-emulsified, and then sterilized with a UHT sterilizer at 145 ° C. for 4 seconds. Next, after vacuum cooling, the mixture was homogenized with a homogenizer at a pressure of 10 MPa, and further cooled to 10 ° C. to obtain concentrated milk for processing.
<Example 6>

Production of mayonnaise 10 parts by weight of brewed vinegar, 1 part by weight of salt, 0.6 parts by weight of sugar, 0.2 parts by weight of mustard powder and 0.2 parts by weight of sodium glutamate are added to the mixer at 15-20 ° C. The aqueous phase was prepared by stirring and mixing. Thereafter, 68 parts by weight of rice white oil, 10 parts by weight of egg yolk to 10 parts by weight of the MCT solution of Example 1, and 15 to 20 ° C. while gradually adding an emulsion (10 to 15 ° C.) obtained by stirring and emulsification. Stirring below and pre-emulsified. Subsequently, final emulsification was performed using a colloid mill to obtain mayonnaise.

Claims (9)

  An oil-containing composition for inhibiting carcinogenesis, comprising a solution obtained by bringing a licorice hydrophobic extract into contact with an oil.   The composition according to claim 1, which is an amount capable of ingesting 0.45 to 3.6 mg / kg body weight per day as an adult licorice hydrophobic extract.   The composition of Claim 1 in which fats and oils contain the glycerol fatty acid ester containing medium chain fatty acid triglyceride and / or fatty acid partial glyceride.   The composition of Claim 1 in which fats and oils contain the glycerol fatty acid ester which contains 50 weight% or more of medium chain fatty acid triglycerides.   The composition of Claim 4 in which fats and oils contain the glycerol fatty acid ester which contains 50 weight% or more of fatty acid partial glycerides.   The composition according to any one of claims 1 to 5, which is for food and drink.   The composition according to any one of claims 1 to 5, which is for use in medicine.   A method for producing a composition for preventing carcinogenesis and / or treating cancer, which comprises contacting a licorice hydrophobic extract with fats and oils. A method for preventing carcinogenesis, comprising administering, as an active ingredient, a solution obtained by bringing a licorice hydrophobic extract into contact with fats and oils.