JP4124952B2 - Cancer metastasis inhibitor and food and drink containing the same - Google Patents

Description

【００３６】
（１）から（４）までを均一に混合した後に、（５）を添加してさらに混合し、その混合末を打錠して、１錠２００ｍｇの錠剤とした。この錠剤は、必要に応じて、通常用いられる胃溶性フィルムコーティング剤（例えば、ポリビニルアセタールジエチルアミノアセテート）または食用性着色剤でコーティングすることも可能である。
【００３７】
〔実施例４〕カプセル剤
（１）実施例１のカカオハスクＰ１画分 １０００ｇ
（２）乳糖 ９６０ｇ
（３）ステアリン酸マグネシウム ４０ｇ
【００３８】
上記成分を均一に混合し、その混合粉末をハードゼラチンカプセルに２００ｍｇずつ充填した。
【００３９】
〔実施例５〕注射剤
（１）実施例１のカカオハスクＰ１画分 １００ｍｇ
（２）ブドウ糖 １００ｍｇ
（３）注射用水 全量で１０ｍｌ
【００４０】
（１）と（２）を（３）に溶解した液をメンブランフィルターで濾過後、再び除菌濾過を行い、その濾過液を無菌的にバイアルに分注し、窒素ガスを充填し密封して静脈内注射剤とした。
【００４１】
〔実施例６〕シロップ剤
（１）実施例１のカカオハスクＰ１画分 ５０ｇ
（２）単シロップ １００ｍｌ
（３）精製水 全量で３００ｍｌ
【００４２】
（１）を（３）で完全に溶解し、（２）を加えて混合し、シロップ剤とした。
【００４３】
〔実施例７〕坐剤
（１）実施例１のカカオハスクＰ１画分 ２ｇ
（２）ウイテプゾール ２００ｇ
【００４４】
（２）を１２０℃、３０分加熱し、室温で５０〜６０℃まで冷却し、これに（１）を加えて十分に混和して均一とし、坐剤型に注入、放冷、固化して１００個の坐剤とした。
【００４５】
〔実施例８〕錠剤

【００４６】
実施例３と同様に調製し、錠剤とした。
【００４７】
〔実施例９〕カプセル剤
（１）実施例１のカカオハスクＰ２画分 １０００ｇ
（２）乳糖 ９６０ｇ
（３）ステアリン酸マグネシウム ４０ｇ
【００４８】
実施例４と同様に調製し、カプセル剤とした。
【００４９】
〔実施例１０〕チューインガム
ガムベース５００ｇ、砂糖１．２ｋｇ、水飴２００ｇ、軟化剤２０ｇ、色素２０ｇ、酸味料２０ｇ、香料２０ｇ、及び実施例１のカカオハスクＰ１画分２０ｇを練り合わせ、常法によりチューインガムを製造した。テクスチャー、風味ともに良好で、癌転移抑制用として日常的に摂取し得るチューインガムであった。
【００５０】
〔実施例１１〕チョコレート
カカオマス３．５ｋｇ、カカオバター１．５ｋｇ、全脂粉乳０．４ｋｇ、砂糖４．５ｋｇ、及び実施例１のカカオハスクＰ１画分０．１ｋｇを混合機に入れ、３８〜４３℃で３０分混合後、リファイナーに移し、３５〜３６℃で粒子が４０μ以下になるように均一に微細化した。次いでコンチングマシンに移して、約６０℃に加温しながら４０時間攪拌混和し、コンチング終了直前に乳化剤としてレシチン５０ｇと若干の香料を加えて均質化した後、２７〜３２℃でテンパリングを行なった。これを所定のモールドに入れ、冷却固化させてチョコレートを製造した。風味が良好で、癌転移抑制用として日常的に摂取し得るチョコレートであった。
【００５１】
〔実施例１２〕キャラメル
砂糖１５０ｇ、水飴１５０ｇ、練乳６０ｇ、小麦粉１８．８ｇを混合し１２０℃まで煮詰めて後、実施例１の方法で得られたカカオハスクＰ２画分２．０ｇ、バター２．２ｇ、カカオバター１．６ｇ、椰子油２．２ｇ、香料１ｇを加えて攪拌後、冷却、成形してキャラメルを製造した。口溶け、風味ともに良好で、癌転移抑制用として日常的に摂取し得るキャラメルであった。
【００５２】
〔実施例１３〕ウーロン茶
定法により製造したウーロン茶１リットルに実施例１で得られたカカオマスＰ２画分１ｇを添加し、癌転移抑制用のウーロン茶飲料を製造した。風味が良好で、癌転移抑制用として日常的に摂取し得るウーロン茶飲料であった。
【００５３】
【発明の効果】
本発明の有効成分であるカカオ豆及び／またはカカオ豆の外皮からアルカリ性水溶液で抽出して得られる抽出物は、副作用がなく安全であり、優れた癌浸潤抑制効果を有するので、癌転移抑制剤として各種癌の転移予防に有用である。
【図面の簡単な説明】
【図１】本発明の癌転移抑制剤であるカカオマスＰ１画分による癌浸潤抑制効果を示したグラフである。
【図２】本発明の癌転移抑制剤であるカカオマスＰ２画分による癌浸潤抑制効果を示したグラフである。
【図３】本発明の癌転移抑制剤であるカカオハスクＰ１画分による癌浸潤抑制効果を示したグラフである。
【図４】本発明の癌転移抑制剤であるカカオハスクＰ２画分による癌浸潤抑制効果を示したグラフである。[0001]
BACKGROUND OF THE INVENTION
The present invention is obtained by extracting a cocoa bean pressed product and / or cocoa bean shell with hexane and further extracting the extraction residue after extraction with hot water into a 0.3N sodium hydroxide solution. The extract is adjusted to pH 5.0 with acetic acid, and then the obtained precipitate is dissolved in water, followed by dialysis and drying .
[0002]
[Prior art]
Cancer, ischemic heart disease, renal failure, and other diseases have been clarified to involve radicals generated in vivo, and plant polyphenols with a strong radical scavenging action clearly have a preventive effect on these diseases It is being done. For example, it is already known that polyphenols contained in tea and red wine have a carcinogenic inhibitory effect.
[0003]
Polyphenols are also contained in cocoa beans used as raw materials for chocolate, cocoa, etc., and as a prior art using this polyphenol as an active ingredient, Japanese Patent Application Laid-Open No. 9-224606 discloses extraction from cocoa beans with ethanol. A health food or drink containing the obtained carcinogenic preventive substance is disclosed.
[0004]
However, the preventive effect of polyphenols such as cocoa beans is aimed at preventing carcinogenesis, which suppresses the occurrence of cancer, and prevents the cancer from expanding and advancing by suppressing the metastasis of already generated cancer cells. It is not intended for patients who already have cancer.
[0005]
JP-A-3-205402 and JP-A-4-13684 disclose that a novel lignin glycoside obtained from pine cones, tea, grass seeds, mitsune, etc. specifically suppresses oncogene expression. And its use as a cancer therapeutic agent is disclosed. Specifically, in mouse breast cancer cells into which a mouse mammary tumor virus (MMTV) gene has been introduced, the expression of MMTV gene is triggered by a depoly ADP-ribose reaction in chromatin protein. By inhibiting ribose) glycohydrolase with the above lignin glycoside, the oncogene expression is suppressed and used as a cancer therapeutic agent.
[0006]
However, the inhibition of poly (ADP-ribose) glycohydrolase by lignin glycosides obtained from pine cones, tea, grass seeds, mitsune, etc. suppresses the oncogene expression stage and suppresses cancer metastasis. In addition, it is difficult to obtain the raw material because the extraction residue treated with hot water, ethanol, acetone or other solvent is prepared by alkali extraction, ethanol precipitation, or gel filtration. And there are problems such as low content of lignin glycosides.
[0007]
In addition, surgical treatment, radiation therapy, chemotherapy (drug administration) and the like are generally performed as cancer treatment methods. Among these, chemotherapy has been widely applied as a therapeutic method in which an agent that directly kills cancer cells is conventionally applied, and many proposals have been made regarding anticancer agents used in this chemotherapy. However, the treatment with an anticancer agent has a disadvantage that side effects are very strong because the anticancer agent acts not only on cancer cells but also on normal cells. In addition, anticancer drugs are highly toxic, so there are limits to high doses and long-term repeated administration, and conventional treatment with chemotherapy cannot be expected to be effective in terms of cancer metastasis, suppression of recurrence, and life extension. Is the current situation.
[0008]
Therefore, in cancer treatment, there are high expectations for drugs and treatment methods that prevent cancer metastasis, can be administered for a long time, and have an excellent therapeutic effect.
[0009]
The molecular mechanism of cancer metastasis is thought to go through the following process. (1) Cancer cells with metastatic potential detach from the tumor mass, (2) move through the interstitial tissue, and (3) adhere to the basement membrane of the blood vessel. (4) The adhering cancer cells decompose and destroy the basement membrane, and further invade the blood vessel lumen. (Referred to as infiltration) (5) Furthermore, cancer cells migrate through blood vessels and selectively adhere to vascular endothelial cells of the target organ. (6) The adhering cancer cells degrade the basement membrane of the blood vessels, destroy them, and further migrate into the target organ. (7) Then, it engrafts and proliferates in a new environment, and further forms a new metastatic focus (Japan Clinical Volume 53, No. 7, 1571-1577 [1995]).
[0010]
Therefore, in order to suppress cancer metastasis, any of the processes described above may be suppressed, which is important as one of cancer treatment methods. Conventionally known cancer metastasis inhibitors include (1) angiogenesis inhibitors (angiostatin, interferon α, thrombospondin, platelet factor 4, TNP-470, pentosan polysulfate, etc.) (2) cells Adhesion inhibitors (RGDS-related peptides, YIGSR-related peptides, SCM chitin, nojirimycin, tunicamycin, etc.) (3) Platelet aggregation inhibitors (cycaprost, indomethacin, antistasin, etc.) (4) Signal transduction inhibitors and motility regulators (Carboxamide-triazole, MDL-27032, verapamil, diltiazem, etc.) (5) Extracellular matrix degrading enzyme inhibitor (batimastat, FOY-305, retinoid, interferon β, etc.) (6) Immunotherapeutic agent (CGP-19835A, BCG, OK (Pharmacia 31:10, 1132-1137 [1995]), however, drugs intended to suppress metastasis of this cancer target only some cancers (interferon-α). Is Kaposi's sarcoma, and suramin is currently recognized for clinical application as prostate cancer [Cancer Chemotherapy Handbook 3rd Edition, Nao Furue et al., Pages 95-96, Medical Science International, Inc.].
[0011]
Recently, several drugs that inhibit cancer cell metastasis have entered the clinical trial stage. One of them is marimastat which suppresses metastasis by inhibiting matrix metalloprotease which is an extracellular matrix degrading enzyme that is important in the invasion process of cancer cells (Pharmacia 34, No. 10, pages 995-997 [1998]). ). However, although not serious, this drug has joint pain, muscle pain and gastrointestinal side effects.
[0012]
Furthermore, as shown above, angiogenesis inhibition is also important in suppressing cancer metastasis. Recently, plasminogen and collagen fragmentation peptides, which are endogenous angiogenesis inhibitors found in tumor cells, have recently been found. Angiostatin and endostatin are attracting attention (Chemistry and Biology, Vol. 37, No. 5, pp. 306-311 [1999]).
[0013]
Furthermore, as a research stage, there is a peptide derivative of a fibronectin molecule as a cancer metastasis inhibitor, but a considerably high concentration is required to suppress invasion.
[0014]
Thus, in the prior art, no substance having sufficient action as a cancer metastasis inhibitor and having sufficient safety has been found, and there are few drugs used in the clinic.
[0015]
[Problems to be solved by the invention]
An object of the present invention is to provide a cancer metastasis inhibitor that has no side effects and is safe and has an excellent cancer metastasis inhibitory effect, and a food and drink containing the same.
[0016]
[Means for Solving the Problems]
As a result of intensive studies to solve the above problems, the present inventors have obtained an extract obtained by extraction with cacao beans and / or cocoa bean hulls with an alkaline aqueous solution, or cocoa beans and / or cocoa bean hulls. If the extract obtained by extraction with an alkaline aqueous solution from the extraction residue after extraction by adding water or an organic solvent to, it is found that it is safe without side effects and has an excellent cancer metastasis inhibitory effect, The present invention has been completed.
[0017]
That is, the present invention is a cancer metastasis inhibitor obtained by extraction with cacao beans and / or shells of cacao beans with an alkaline aqueous solution, and a food and drink containing the same.
[0018]
Moreover, as a preferable aspect, the precipitate obtained by making the said extract into the weakly acidic range of pH 4-6, or the precipitate obtained by making the pH from 4 to 6 into the weakly acidic range is removed. After the caking, by using a precipitate formed by adding an organic solvent to the extract as an active ingredient, metastasis of cancer can be suppressed very effectively.
[0019]
Therefore, the active ingredient of the present invention is different from the ethanol-soluble extractable ingredient of cacao beans described in JP-A-9-24606 as a prior art.
[0020]
DETAILED DESCRIPTION OF THE INVENTION
The extract obtained by extraction with cacao beans and / or cocoa bean hulls, which are the active ingredients of the present invention, with an alkaline aqueous solution is the endosperm (cacao nibs) of cacao (Theobroma Cacao L.), which is a small Takagi tree And / or its outer skin (cocoa husk) as a raw material, this is extracted with an alkaline aqueous solution, for example, 0.1 to 1N sodium hydroxide, ammonium hydroxide, potassium hydroxide, etc. for 1 to 15 hours.
[0021]
Alternatively, the cocoa beans or cocoa bean hulls are first extracted with water, hot water, alcohols such as ethanol, ketones such as acetone, organic solvents such as hexane, or a mixed solvent thereof, and the alkaline residue is extracted from the extraction residue. You may extract by aqueous solution. In addition, the extraction process of the first water, hot water, or organic solvent can also be repeatedly extracted with another kind of solvent.
[0022]
Furthermore, in the present invention, preferably, the alkaline aqueous extract is adjusted to a slightly acidic range of 4 to 6 with acetic acid, hydrochloric acid or the like, and a precipitate obtained after standing for about 30 minutes to overnight is used as an active ingredient. And effective. Moreover, it is also possible to use the precipitate which arises by adding an organic solvent and leaving still for a whole day and night for the component which is melt | dissolving even if it adjusts to the range of weak acidity. As the organic solvent used in this case, alcohols, acetones, or hydrates thereof can be used, but it is optimal to add ethanol so that the concentration is preferably 50% or more.
[0023]
In the present invention, either cocoa beans or cocoa bean hulls may be selected and used as a raw material as necessary, but they can also be used by appropriately mixing them.
[0024]
The cancer metastasis inhibitor comprising the cacao bean of the present invention and / or its alkaline extract as an active ingredient has an effect of inhibiting cancer metastasis, and therefore various cancers such as malignant melanoma, uterine cancer, esophageal cancer, skin It can be used as a metastasis inhibitor for malignant tumors such as cancer, stomach cancer, lung cancer, small intestine / colon cancer, pancreatic cancer, breast cancer, bladder cancer, choriocarcinoma, lymphosarcoma, leukemia and the like.
[0025]
In addition, the cancer metastasis inhibitor of the present invention can be administered to mammals including humans (human, horse, dog, cow, pig, etc.) and the like. May vary depending on the age, body weight and severity of the disease condition to be treated, response to treatment, administration method and number of administrations. For example, in the case of oral administration, usually about 0.3 to 30 mg / kg body weight is once a day. Or administer several times. Use of a concentration lower than 0.3 mg / kg may have an insufficient effect.
[0026]
Furthermore, the cancer metastasis inhibitor of the present invention is obtained by mixing the active ingredient of the present invention and an additive for pharmaceutical preparation such as a pharmaceutically acceptable carrier in the form of a pharmaceutical preparation, orally or parenterally (transdermally). Intravenous, rectal, etc.). Examples of the dosage form include tablets, capsules, powders, suppositories, liquids, rectal ointments, injections and the like, but are not necessarily limited to these dosage forms.
[0027]
As content in the said pharmaceutical formulation of the active ingredient in this invention, although it is difficult to prescribe | regulate unconditionally by the form, a capacity | capacitance, etc., Preferably it is 1 to 90 weight%.
[0028]
The cacao beans or cacao bean hulls used in the present invention are abundant in natural products and can be easily collected. Therefore, the cancer metastasis inhibitor of the present invention has a complex process of synthesizing like marimastat. In addition, genetic recombination procedures such as Angiostatin and Endostatin are not necessary, and it is practical because it can be produced at low cost without labor and cost in production. Furthermore, cocoa beans or their outer shells are used as foods, and the active ingredient of the present invention is safe and non-toxic.
[0029]
Examples are given below to describe the present invention in detail, but the present invention is not limited to these Examples.
[0030]
【Example】
[Example 1] Preparation of an agent for inhibiting cancer metastasis from cocoa beans and cocoa beans hulls Cacao beans (cacao nibs) pressed products (cacao mass) or cacao bean hulls (cacao husk) each added with 2.5 l of hexane, After stirring all day and night, the mixture was filtered. To the residue, 2.5 l of hexane was added and stirred again all day and night. It was filtered to obtain 133 g and 270 g of degreased product, respectively. To each 25 g of the defatted product, 250 ml of hot water was added and boiled for 1 hr. It was centrifuged (10,000 g × 20 min), and the residue was similarly extracted with hot water. To the obtained hot water extraction residue, 250 ml of 0.3N sodium hydroxide solution was added, and extracted all day and night. It was centrifuged (10,000 g × 20 min), and the resulting extract was adjusted to pH 5.0 with acetic acid and allowed to stand at 4 ° C. overnight. Centrifugation (10,000 g × 20 min), the resulting precipitate was dissolved in water, dialyzed overnight and freeze-dried, and the cacao mass P1 fraction, which is an extract derived from cocoa beans and cocoa bean hulls, cacao husk P1 1.4 g and 0.8 g of fractions were obtained, respectively. The filtrate was adjusted to pH 5.0 with acetic acid, allowed to stand at 4 ° C. for one day and then centrifuged, and the same amount of ethanol was added and left at 4 ° C. for one day. This was centrifuged (10,000 g × 20 min), the obtained precipitate was dissolved in water, dialyzed and freeze-dried, and the cocoa beans and cocoa bean hull-derived extracts derived from cocoa mass P2 and cocoa husk P2 were obtained. 0.61 g and 0.74 g were obtained, respectively.
[0031]
[Example 2] Cancer invasion inhibitory effect test Human pancreatic cancer cell line MIA PaCa-2 (showing high invasion ability) maintained in culture in DMEM medium containing 10% FCS was recovered with trypsin-EDTA, washed, 1 It was suspended in a DMEM medium containing% FCS and used for an infiltration capacity measurement system.
[0032]
The invasive ability was measured using a dual-structure 96-well chemotaxis chamber. A human plasma-derived fibronectin was coated on a polycarbonate filter having a pore size of 8 μm, air-dried, and further overlaid with Matrigel composed of components of the extracellular matrix. A DMEM medium containing 1% FCS was injected into the lower layer of the chemotaxis chamber, and the previous polycarbonate filter was mounted thereon to swell fibronectin at 37 ° C. for about 2 hours. Thereafter, MIA PaCa-2 suspended in DMEM medium containing 1% FCS in the upper layer was seeded at 1 × 10 ⁵ cells, and the chemotaxis chamber was shaken lightly so as to be uniform on Matrigel. The cocoa mass P1, P2 fraction or the cocoa husk P1, P2 fraction was heated in a DMEM medium not containing FCS at 60 ° C. for 15 minutes, and after lysis, it was added to the cells in the upper layer so that each final concentration was obtained. The chemotaxis chamber was incubated at 37 ° C. in a 5% CO ₂ incubator for 24 hours.
[0033]
Cells infiltrating the lower surface of the polycarbonate filter were fixed with methanol, and after staining with hematoxylin-eosin, the number of cells was counted under a microscope. The number of infiltrating cells was measured in 10 fields at a magnification of 400 times and expressed as the average number of cells per field.
[0034]
FIG. 1 shows the MIA PaCa-2 cell invasive ability inhibitory effect of the cacao mass P1 fraction. The cacao mass P1 fraction was suppressed in a concentration-dependent manner, and a significant inhibitory effect was observed at 30 μg / ml. FIG. 2 shows the results of the cocoa mass P2 fraction. Although the effect was weaker than that of the cocoa mass P1 fraction, it was suppressed in a concentration-dependent manner and showed a significant inhibitory effect at 100 μg / ml. FIG. 3 shows the results of the cacao husk P1 fraction. Similar to the cacao mass P1 fraction, it was suppressed in a concentration-dependent manner and had a significant inhibitory effect at 30 μg / ml. FIG. 4 shows the results of the cacao husk P2 fraction. Although the effect was weaker than the cacao husk P1 fraction, it was suppressed in a concentration-dependent manner and showed a significant inhibitory effect at 100 μg / ml.
[0035]
[Example 3] Tablet

[0036]
After uniformly mixing (1) to (4), (5) was added and further mixed, and the mixed powder was tableted to give a tablet of 200 mg. If necessary, the tablet can be coated with a commonly used gastric film coating agent (for example, polyvinyl acetal diethylaminoacetate) or an edible colorant.
[0037]
[Example 4] Capsule (1) 1000 g of cocoa husk P1 fraction of Example 1
(2) Lactose 960g
(3) Magnesium stearate 40g
[0038]
The above ingredients were mixed uniformly, and the mixed powder was filled into hard gelatin capsules 200 mg each.
[0039]
[Example 5] Injection (1) Cacao husk P1 fraction of Example 1 100 mg
(2) Glucose 100mg
(3) Water for injection 10ml in total
[0040]
Filter the solution in which (1) and (2) are dissolved in (3) with a membrane filter, perform sterilization filtration again, aseptically dispense the filtrate into vials, fill with nitrogen gas and seal. It was an intravenous injection.
[0041]
[Example 6] Syrup (1) Cacao husk P1 fraction of Example 1 50 g
(2) Single syrup 100ml
(3) Purified water 300ml in total
[0042]
(1) was completely dissolved in (3), and (2) was added and mixed to obtain a syrup.
[0043]
[Example 7] Suppository (1) 2 g of the cacao husk P1 fraction of Example 1
(2) Uitepsol 200g
[0044]
Heat (2) at 120 ° C. for 30 minutes, cool to 50-60 ° C. at room temperature, add (1) to this and mix thoroughly to make it uniform, inject into a suppository mold, allow to cool, solidify There were 100 suppositories.
[0045]
[Example 8] Tablet

[0046]
Prepared in the same manner as in Example 3 to obtain tablets.
[0047]
[Example 9] Capsule (1) 1000 g of cocoa husk P2 fraction of Example 1
(2) Lactose 960g
(3) Magnesium stearate 40g
[0048]
A capsule was prepared in the same manner as in Example 4.
[0049]
[Example 10] Chewing gum gum base 500 g, sugar 1.2 kg, starch syrup 200 g, softener 20 g, pigment 20 g, acidulant 20 g, flavoring 20 g, and cacao husk P1 fraction 20 g of Example 1 were kneaded together to produce chewing gum by a conventional method. did. The chewing gum has good texture and flavor and can be ingested on a daily basis to suppress cancer metastasis.
[0050]
[Example 11] 3.5 kg of chocolate cacao mass, 1.5 kg of cacao butter, 0.4 kg of whole milk powder milk, 4.5 kg of sugar, and 0.1 kg of cacao husk P1 fraction of Example 1 were placed in a mixer. After mixing at 30 ° C. for 30 minutes, the mixture was transferred to a refiner and uniformly refined at 35 to 36 ° C. so that the particles were 40 μm or less. Next, the mixture was transferred to a conching machine, stirred and mixed for 40 hours while heating to about 60 ° C., and immediately before the completion of conching, 50 g of lecithin and a slight fragrance were added and homogenized, and then tempered at 27 to 32 ° C. . This was put into a predetermined mold and cooled and solidified to produce chocolate. The chocolate had a good flavor and can be taken on a daily basis to suppress cancer metastasis.
[0051]
[Example 12] After mixing 150 g of caramel sugar, 150 g of starch syrup, 60 g of condensed milk, and 18.8 g of flour and boiled to 120 ° C., 2.0 g of cacao husk P2 fraction obtained by the method of Example 1 and 2.2 g of butter Then, 1.6 g of cacao butter, 2.2 g of coconut oil, and 1 g of fragrance were added, stirred, cooled, and molded to produce caramel. It was a caramel that melted in the mouth and tasted well, and that can be taken on a daily basis to suppress cancer metastasis.
[0052]
[Example 13] 1 g of the cocoa mass P2 fraction obtained in Example 1 was added to 1 liter of oolong tea produced by the conventional method of oolong tea to produce a oolong tea beverage for suppressing cancer metastasis. It was a oolong tea beverage with a good flavor and that can be taken on a daily basis to suppress cancer metastasis.
[0053]
【The invention's effect】
The extract obtained by extraction with cacao beans and / or cocoa bean hulls, which are active ingredients of the present invention, with an alkaline aqueous solution is safe with no side effects and has an excellent cancer infiltration inhibitory effect. It is useful for preventing metastasis of various cancers.
[Brief description of the drawings]
BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a graph showing the cancer infiltration inhibitory effect of a cacao mass P1 fraction that is a cancer metastasis inhibitor of the present invention.
FIG. 2 is a graph showing the cancer invasion inhibitory effect of the cacao mass P2 fraction, which is a cancer metastasis inhibitor of the present invention.
FIG. 3 is a graph showing the cancer invasion inhibitory effect of cacao husk P1 fraction, which is a cancer metastasis inhibitor of the present invention.
FIG. 4 is a graph showing the cancer invasion inhibitory effect of cacao husk P2 fraction, which is a cancer metastasis inhibitor of the present invention.

Claims (2)

An extract obtained by extracting with a 0.3N sodium hydroxide solution to an extraction residue obtained by further adding hot water to the extracted residue after adding hexane to the cocoa bean pressed product and / or cocoa bean shell, A cancer metastasis inhibitor comprising, as an active ingredient, an extract obtained by adjusting pH 5.0 with acetic acid, dissolving the resulting precipitate in water, and drying after dialysis . An extract obtained by extracting with a 0.3N sodium hydroxide solution to an extraction residue obtained by further adding hot water to the extracted residue after adding hexane to the cocoa bean pressed product and / or cocoa bean shell, A cancer metastasis characterized by comprising an extract obtained by adding ethanol to the filtrate obtained after adjusting to pH 5.0 with acetic acid, dissolving the precipitate obtained in water, and drying after dialysis. Inhibitor.

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