JP2006280300A - Bilberry-mixed food having tumor cell antiproliferating effect and method for producing the same - Google Patents
Bilberry-mixed food having tumor cell antiproliferating effect and method for producing the same Download PDFInfo
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Abstract
Description
本発明は、腫瘍細胞増殖抑制効果を持つビルベリー配合食品、特にその効果を期待できるビルベリー配合健康飲料およびその製造方法に関するものである。 The present invention relates to a bilberry-containing food having a tumor cell growth-inhibiting effect, particularly to a bilberry-containing health drink that can be expected to have the effect, and a method for producing the same.
主として、ヨーロッパ等で栽培されてきたビルベリーは、古くから鮮やかな赤色や紫色等いわゆるビルベリー色の色素特性を利用することに多く用いられてきた。また、近年はその薬効に関する論文が発表され、主として、眼精疲労回復、視力回復や血管の透過性等に有効であるとするこの種の研究も進んでいる。
また、昨今ビルベリーを含有する飲料についても、色々開発がすすめられている。（例えば、特許文献１参照）
Recently, various beverages containing bilberries have been developed. (For example, see Patent Document 1)
また、前記薬効もビルベリーから抽出されたビルベリーエキスの含有量によりその効果が異なり、視力治療、回復や毛細血管の浸透性の低減などには、或る所定の濃度のビルベリーエキスが必要であることがわかっている。しかしながら、従来ビルベリーエキスはその溶解度に難があるため、その処方は粉末乃至粉末を固めた錠剤の形で服用されているのが現実であった。従って、より服用し易くかつ、薬効を示すい所定の濃度のアントシアニジンを含む液体処方としてのものが強く要求されている。 In addition, the medicinal effect varies depending on the content of bilberry extract extracted from bilberry, and a certain amount of bilberry extract is necessary for the treatment of vision, recovery, reduction of capillary permeability, etc. I know. However, since the bilberry extract has a difficulty in solubility, it was actually taken in the form of a powder or a powdered tablet. Accordingly, there is a strong demand for a liquid formulation containing anthocyanidin at a predetermined concentration that is easier to take and exhibits medicinal properties.
今世紀における高死亡率を占める各種のがん疾患は、消化器系、呼吸器系を初めとして身体のあらゆる部分へと拡大されてきており、先端医学による初期のがん疾患の検出技術、抗がん剤の進歩等とそれなりの成果は認められるものの、副作用を含めこれらが必ずしも十分に対処されているとは言い得ず、大きな社会問題となってきている。 The various cancer diseases that occupy a high mortality rate in this century have been extended to every part of the body, including the digestive system and respiratory system. Although progress in cancer drugs and some results have been recognized, it cannot be said that these have been adequately addressed, including side effects, and has become a major social problem.
一般的にがん疾患に対する考え方としては、当然予防的対処および治療的対処とがあり、この内、治療的対処としては、（１）外科的手法によるがん細胞・組織の除去、（２）化学療法・放射線療法によるがん細胞の増殖阻止、および（３）新しい細胞免疫療法などがある。しかしながら、侵襲性、副作用などの点から、患者の苦痛を軽減する新しい治療法の開発が求められている。
特に、近年その手法の一つとして、健康食品による漢方医学的な予防的対処が脚光を浴びてきており、アガリスク茸を含有する健康食品などはこれらの最たるものとして認められてきている。しかしこのアガリスク茸系の健康食品もそれが効果ありとするためには価格的に問題がある。
他方、本出願人は、多くの実験の結果、従来視力治療、回復に効果ありとして認められているビルベリー果実より抽出標準化した所定量のビルベリーエキスが、がん細胞、特に白血球系由来腫瘍細胞および消化器系由来腫瘍細胞に顕著なる細胞増殖抑制作用を示す知見を得た。
In general, there are naturally preventive measures and therapeutic measures as a way of thinking about cancer diseases. Among these, the therapeutic measures include (1) removal of cancer cells / tissues by a surgical technique, (2) There are cancer cell growth inhibition by chemotherapy and radiation therapy, and (3) new cellular immunotherapy. However, there is a need for the development of new therapies that reduce patient pain in terms of invasiveness and side effects.
In particular, as one of the methods in recent years, herbal medicine preventive measures using health foods have been spotlighted, and health foods containing agaris koji have been recognized as the best of these. However, this agarisk-based health food also has a price problem in order to be effective.
On the other hand, as a result of many experiments, the present applicant has found that a predetermined amount of bilberry extract extracted and standardized from bilberry fruit, which has been recognized as effective in the treatment and recovery of vision, has cancer cells, particularly leukocyte-derived tumor cells and The present inventors have obtained knowledge that shows a remarkable cell growth inhibitory effect on digestive system-derived tumor cells.
本発明は由来の異なる腫瘍細胞に対する増殖抑制効果、しかも、安価で且つ服用し易いビルベリーエキスを用いた配合健康飲料、およびその製造方法が望まれており、本発明はこれらを提供することを、その目的としている。 The present invention is desired to have a growth-suppressing effect on tumor cells having different origins, and a blended health drink using a bilberry extract that is inexpensive and easy to take, and a method for producing the same, and the present invention provides these, That is the purpose.
本発明の腫瘍細胞増殖抑制効果をもつビルベリー配合食品は、
１） ビルベリー果実より抽出標準化された、アントシアニジンを２５％以上含有するビルベリーエキスを１ｍｌ当たり０．１〜１．０μｇ含有するものであり、
２） 上述の１）において、ビルベリー果実より抽出標準化された、アントシアニジンを２５％以上含有するビルベリーエキスを１ｍｌ当たり０．１〜１．０μｇ含有し、さらに少なくともビルベリー調合香料と、糖類、酸味料、および添加物を配合したビルベリー飲料としたものであり、
３） 上述の２）において、前記酸味料をクエン酸とし、糖類を少なくともブドウ糖、果糖、麦芽糖から選ばれた糖類としたビルベリー飲料としたものであり、
４） 上述の２）において、前記添加物として腫瘍細胞増殖抑制作用の相乗効果が期待できる少なくとも 種々のビタミン類、又は／およびアミノ酸を加えたビルベリー飲料としたものである。
Bilberry-containing food having the tumor cell growth inhibitory effect of the present invention,
1) 0.1 to 1.0 μg per ml of bilberry extract containing 25% or more of anthocyanidin extracted and standardized from bilberry fruit,
2) In the above 1), 0.1 to 1.0 μg per ml of bilberry extract containing 25% or more of anthocyanidin extracted and standardized from bilberry fruit, and at least bilberry blended flavor, sugars, acidulant, And a bilberry beverage containing additives,
3) In the above 2), the acidulant is citric acid, and the saccharide is a bilberry drink having at least saccharide selected from glucose, fructose and maltose,
4) In the above 2), the additive is a bilberry beverage to which at least various vitamins and / or amino acids that can be expected to have a synergistic effect of suppressing tumor cell growth are added.
本発明の腫瘍細胞増殖抑制作用を有するビルベリー配合食品の製造方法は、
５） ビルベリー果実を圧縮粉砕する第１工程と、該圧縮粉砕されたビルベリー砕体より抽出、標準化して概ね２５％のアントシアニジンを含む粉体のビルベリーエキスを生成する第２工程と、該粉体のビルベリーエキスを８５〜１００℃の高温水にて攪拌、溶解しビルベリーエキスを１００ｍｌ当たり１０，０００ｍｇ以上含有するビルベリーエキストラクト（原液）とする第３工程と、該ビルベリーエキストラクト（原液）にビルベリー調合香料、糖類、酸味料および少なくとも種々のビタミン類、又は／およびアミノ酸を添加物として加えてビルベリー飲料原液とする第４工程と、該ビルベリー飲料原液を、最終アントシアニジンを０．０２５〜０．２５ｍｇ／ｍｌ相当含有するようにろ過滅菌したリン酸緩衝液（ｐH７．０）に溶解し混合添加してビルベリー配合飲料とする第５工程を有するものである。
The method for producing a bilberry-containing food having tumor cell growth inhibitory action of the present invention,
5) a first step of compressing and crushing bilberry fruit; a second step of extracting and standardizing from the compressed and ground bilberry crushed material to produce a powdered bilberry extract containing approximately 25% anthocyanidins; and the powder The bilberry extract was stirred and dissolved in high temperature water at 85 to 100 ° C. to obtain a bilberry extract (stock solution) containing 10,000 mg or more of bilberry extract per 100 ml, and the bilberry extract (stock solution) was converted into bilberry. A fourth step of adding a blended flavor, sugar, acidulant and at least various vitamins or / and amino acids as additives to form a bilberry beverage stock solution, and 0.025 to 0.25 mg of the final anthocyanidin solution. / Ml in phosphate buffer (pH 7.0) sterilized by filtration so as to contain the equivalent amount And if added are those having a fifth step of the bilberry blended beverage.
本発明は、 ビルベリー果実より抽出標準化された、アントシアニジンを２５％以上含有するビルベリーエキスを１ｍｌ当たり０．１〜１．０μｇ含有し、 さらに少なくともビルベリー調合香料と、糖類、酸味料、および添加物として腫瘍細胞増殖抑制作用に相乗効果が期待できる少なくとも種々のビタミン類、又は／およびアミノ酸などを添加物として加えることが可能で、その作用の増強と共に安価で、服用し易い腫瘍細胞増殖抑制作用を有するビルベリー配合健康飲料を提供することが出来る。 The present invention contains 0.1 to 1.0 μg of bilberry extract per ml containing 25% or more of anthocyanidin extracted and standardized from bilberry fruit, and at least as a bilberry blended flavor, sugars, acidulants, and additives. It is possible to add at least various vitamins or / and amino acids that can be expected to have a synergistic effect on the tumor cell growth inhibitory action as an additive, and it is inexpensive and easy to take tumor cell growth inhibitory action with enhanced action A health drink containing bilberry can be provided.
ビルベリーは、植物学的分類におけるツツジ（Ｅｒｉｃａｃｅａｅ）科、スノキ（Ｖａｃｃｉｎｕｍ）属、Ｍｙｔｉｌｌｕｓ節に属する主として北部ヨーロッパ自生する落葉性低木であって、その果実特にその果皮は紫色でアントシアニン色素に富む。このアントシアニンは、シアニジン（Ｃｙａｎｉｄｉｎ）、デルフィニジン（Ｄｅｌｐｈｅｎｉｄｉｎ）、マルビジン（Ｍａｌｖｉｄｉｎ）、ペラルゴニジン（Ｐｅｌａｒｇｏｎｉｄｉｎ）、ペオニジン（Ｐｅｏｎｉｄｉｎ）ペチュニジン（Ｐｅｔｕｎｉｄｉｎ）、の６種のアントシアニジンに、グルコース（ｇｌｕｃｏｓｅ）、ガラクトース（ｇａｌａｃｔｏｓｅ）、アラビノース（ａｒａｂｉｎｏｓｅ）の３つの糖類がそれぞれ１つずつ結合した配糖体よりなる。
このアントシアニンの代表的構造式は次式で示される。
Bilberry is a deciduous shrub that grows mainly in northern Europe, belonging to the family Ericaceae, Vaccinum, Mytilus in the botanical classification, and its fruit, especially its skin, is purple and rich in anthocyanin pigments. The anthocyanins include six types of anthocyanidins such as cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin, glucose (glucose), glucose, glucose, It consists of a glycoside in which three saccharides of arabinose are bonded one by one.
A typical structural formula of this anthocyanin is shown by the following formula.
従来から、ビルベリーの薬効として、眼の網膜活性化効果、毛細血管保護効果、抗酸化作用効果，抗炎症作用効果、抗潰瘍活性効果などが知られている。
本発明は、上記ビルベリーの各種効果に対し、腫瘍細胞、特に白血病由来腫瘍細胞および消化器系由来腫瘍細胞に対する細胞増殖抑制作用効果に焦点を合わせ、特殊の方法により抽出標準化したビルベリーエキスを使用することにより、従来の適用量に較べて極めて低いビルベリー濃度の適用量にて、十分上記作用効果を実現したところにそのポイントがある。
Conventionally, the retinal activation effect, capillary protection effect, antioxidant effect, anti-inflammatory effect, anti-ulcer activity and the like of the eye are known as the medicinal effects of bilberry.
The present invention uses a bilberry extract extracted and standardized by a special method, focusing on the cell growth inhibitory effect on tumor cells, particularly leukemia-derived tumor cells and digestive system-derived tumor cells, against the various effects of bilberries. Therefore, the point is that the above-mentioned effects are sufficiently realized with an application amount of a bilberry concentration that is extremely lower than the conventional application amount.
本発明に使用するビルベリーエキスは、本発明の出願人による特許出願である特願２００３−１５７７２７号「ビルベリー原液の製造方法」に記載されたものをベースとしており、ビルベリー果実を圧縮粉砕し、該圧縮粉砕されたビルベリー砕体より抽出、標準化して２５％以上のアントシアニジンを含有する粉体のビルベリーエキスを使用するものである。
すなわち、ビルベリーエキスラクト（原液）は、ビルベリー果実を圧縮粉砕する第１工程と、該圧縮粉砕されたビルベリー砕体より抽出、標準化して２５％以上のアントシアニジンを含む粉体のビルベリーエキスを生成する第２工程と、該粉体のビルベリーエキスを８５〜１００℃の高温水にて攪拌、溶解しビルベリーエキスを１００ｍｌ当たり１０，０００ｍｇ以上含有するビルベリーエキスラクト（原液）とする第３工程により作成される。
このビルベリーエキスラクト（原液）にビルベリー調合香料、糖類、酸味料および少なくとも種々のビタミン類、又は／およびアミノ酸を添加物として加えてビルベリー飲料原液とする第４工程と、該ビルベリー飲料原液を、最終アントシアニジンを０．０２５〜０．２５μｇ／ｍｌ含有するように混合添加してビルベリー配合飲料とする第５工程により本発明の腫瘍細胞増殖抑制効果をもつビルベリー配合食品は製造される。
The bilberry extract used in the present invention is based on the one described in Japanese Patent Application No. 2003-157727 “Method for producing bilberry stock solution” which is a patent application by the applicant of the present invention. A powdered bilberry extract containing 25% or more of anthocyanidin is extracted and standardized from the crushed bilberry crushed material.
That is, the bilberry extract (stock solution) is a first step of compressing and pulverizing bilberry fruit, and extracting and standardizing from the compressed and pulverized bilberry crushed powder to produce a powdered bilberry extract containing 25% or more anthocyanidins. Prepared by the second step and the third step of stirring and dissolving the powdered bilberry extract in high temperature water of 85 to 100 ° C. to obtain a bilberry extract (stock solution) containing 10,000 mg or more of bilberry extract per 100 ml. The
A fourth step of adding a bilberry blend flavor, sugar, acidulant and at least various vitamins or / and amino acids as additives to the bilberry extract (stock solution) to form a bilberry beverage stock solution, The bilberry-containing food having an inhibitory effect on tumor cell growth of the present invention is produced by the fifth step in which anthocyanidins are mixed and added so as to contain 0.025 to 0.25 μg / ml to obtain a bilberry-containing beverage.
多くの実験の結果、このビルベリーエキスによるビルベリー濃度として１ｍｌ当たり０．２〜１．０μｇ含有する混合液、が顕著な腫瘍細胞増殖抑制効果発現に望ましいことがわかった。
０．２μｇ未満では腫瘍細胞増殖抑制作用効果は殆ど現れず、０．２μｇ以上の濃度において顕著な細胞増殖抑制効果を発現し始める。また１．０１μｇを越えても該効果（９０％以上の細胞において増殖抑制が認められる）はサチュレートしており、意味がない。
従って、ビルベリー濃度としての最適範囲としては、１ｍｌ当たり０．２μｇ〜１．０μｇとすることが望ましい。
As a result of many experiments, it has been found that a mixed solution containing 0.2 to 1.0 μg per ml as a bilberry concentration by this bilberry extract is desirable for a remarkable tumor cell growth inhibitory effect.
If it is less than 0.2 μg, the tumor cell growth inhibitory effect hardly appears, and at a concentration of 0.2 μg or more, a remarkable cell growth inhibitory effect starts to appear. Moreover, even if it exceeds 1.01 microgram, this effect (proliferation suppression is recognized in 90% or more of cells) is saturating, and is meaningless.
Accordingly, the optimum range for the bilberry concentration is desirably 0.2 μg to 1.0 μg per ml.
また、本発明は、抗細胞増殖抑制に対する相乗効果を期待するため、抗酸化作用を有するビタミンＥ（最終濃度１ｍＭ：通常は２００．４００ＩＵを摂取し、１ｍＭはほぼ２５０ＩＵに相当する）を混合すると、その細胞増殖抑制効果は増強されるという知見を得ている。 このことは、該物質とビタミン類、アミノ酸などのサプリメントを添加し、その作用効果の増強が可能という点で新規性がある。 In addition, in the present invention, in order to expect a synergistic effect on the inhibition of anti-cell proliferation, mixing vitamin E having an antioxidant action (final concentration of 1 mM: usually ingesting 200.400 IU, 1 mM corresponding to about 250 IU) It has been found that its cell growth inhibitory effect is enhanced. This is novel in that the substance and supplements such as vitamins and amino acids can be added to enhance the action and effect.
出願人は、上記アントシアニジン成分に注目し、腫瘍細胞の増殖に対する効果の確認試験を行った。
試験がん細胞としては、大腸がん細胞（ＣＯＬＯ２０１）、胃印環細胞がん細胞（ＫＡＴＯ−III）、Ｔリンパ血球系白血病細胞（Ｉ９．１）、単球由来白血病細胞（Ｕ９３７）を用いた。
各がん細胞の細胞株をそれぞれ培養液と混ぜ約106 個の細胞数（２００μｌ）に調製し、９６穴培養用マイクロプレートに播種し、ビルベリーエキスより調製したビルベリー液を培養液の１／１０量（最終濃度：０、０．１、０．３、０．６および１．０μｇ／ｍｌ）加え一定時間（２４時間）インキュベーター（３７℃）中で培養した後生細胞数を計数した。
なお、比較のためヒト正常内皮細胞（ＨＵＶＥＣ）の場合についても、同様の実験を行った。
The applicant paid attention to the anthocyanidin component and conducted a confirmation test of the effect on the growth of tumor cells.
As test cancer cells, colon cancer cells (COLO201), gastric signet ring cell carcinoma cells (KATO-III), T-lymphocytic leukemia cells (I9.1), monocyte-derived leukemia cells (U937) are used. It was.
Each cancer cell line is mixed with the culture solution to prepare about 10 6 cells (200 μl), seeded on a 96-well microplate, and the bilberry solution prepared from the bilberry extract is 1 / of the culture solution. After adding 10 amounts (final concentrations: 0, 0.1, 0.3, 0.6 and 1.0 μg / ml) and culturing in an incubator (37 ° C.) for a fixed time (24 hours), the number of viable cells was counted.
For comparison, the same experiment was performed for human normal endothelial cells (HUVEC).
図１は、本発明の実施例１における、ビルベリー濃度と各種腫瘍由来ガン細胞に対する効果確認試験した結果を示した図である。なお、ビルベリー濃度０．１ｍｇ／ｍｌはアントシアニジン含有量として０．０２５ｍｇ／ｍｌに相当する。
図において、ＨＣＦおよびＨＵＶ（ＨＵＶＥＣ）は正常培養細胞でありそれぞれヒト子宮頸管繊維芽細胞およびヒト内皮細胞、ＣＯＬＯは大腸がん細胞、ＫＡＴＯ−IIIは胃印環がん細胞、Ｕ９３７およびＨＬ−６０は単核球由来白血病細胞、Ａ３およびＩ９．１はＴリンパ球由来白血病細胞の場合である。
FIG. 1 is a graph showing the results of an effect confirmation test on bilberry concentration and various tumor-derived cancer cells in Example 1 of the present invention. The bilberry concentration of 0.1 mg / ml corresponds to 0.025 mg / ml as the anthocyanidin content.
In the figure, HCF and HUV (HUVEC) are normal cultured cells, human cervical fibroblasts and human endothelial cells, COLO is colon cancer cells, KATO-III is gastric signet ring cancer cells, U937 and HL-60, respectively. Is for mononuclear cell-derived leukemia cells, and A3 and I9.1 are for T lymphocyte-derived leukemia cells.
試験結果より、腫瘍細胞の種類によりビルベリエキス濃度による影響は異なっており、白血病由来の細胞の場合は極めて低濃度（０．１μｇ／ｍｌ）から、その細胞増殖抑制効果を発揮し、０．２μｇ／ｍｌ以上で残存生存率約３０％に達しほぼその効果はサチュレートする。
これに対して、大腸がん細胞、胃がん細胞の場合は、アントシアニジン量にほぼ比例して、細胞死滅効果が高くなることがわかった。ただし、１．０μｇ／ｍｌ以上ではこれもサチュレートすることが確認された。
白血病由来の細胞の場合は５０〜７０％程度の細胞死滅が認められ、また消化器系のがん細胞の場合は約２５〜５０％程度のがん細胞死滅が確認され、ビルベリー濃度の増加によりより大きな効果を期待することができる。
なお、正常細胞である内皮細胞（ＨＵＶ）に対しては増殖抑制を示さず、また正常子宮頸管繊維芽細胞（ＨＣＦ）に対してはその増殖を促進することから、該物質は選択的に腫瘍細胞の増殖を抑制する知見を得た。
From the test results, the effect of the Bilberry extract concentration varies depending on the type of tumor cell. In the case of leukemia-derived cells, the cell growth inhibitory effect is exhibited from an extremely low concentration (0.1 μg / ml). The residual survival rate reaches about 30% at 2 μg / ml or more, and the effect is almost saturated.
On the other hand, in the case of colon cancer cells and gastric cancer cells, it was found that the cell killing effect was increased almost in proportion to the amount of anthocyanidins. However, it was confirmed that this also saturates at 1.0 μg / ml or more.
In the case of leukemia-derived cells, cell death of about 50 to 70% is observed, and in the case of cancer cells of the digestive system, cancer cell death of about 25 to 50% is confirmed. Greater effects can be expected.
In addition, since the growth of normal endothelial cells (HUV) is not suppressed and the proliferation of normal cervical fibroblasts (HCF) is promoted, the substance is selectively used as a tumor. The knowledge which suppressed the proliferation of a cell was acquired.
本実施例２は、ビルベリーエキスにさらに添加物としてビタミンＥ（以下、ＶＥという）を大腸がん由来細胞（ＣＯＬＯ２０１）に添加し、ビルベリーエキスと添加物による細胞増殖抑制作用の相乗効果を測定した。
ビルベリー濃度０、０．０１、０．１、０．３、０．６、１．０μｇ／ｍｌ含有の培養液にＶＥ１ｍＭを添加し、２４時間培養後および４８時間培養後の実施例１に準じた方法で、細胞生存率を測定した。
In Example 2, vitamin E (hereinafter referred to as VE) was further added to the bilberry extract as an additive to colon cancer-derived cells (COLO201), and the synergistic effect of the cell growth inhibitory action of the bilberry extract and the additive was measured. .
According to Example 1 after adding
図２は、本発明の実施例２における、ビルベリーエキスにさらに上記添加物を加えた混合液による各種腫瘍由来ガン細胞に対する相乗効果を確認試験した結果を示す図であり、（ａ）は２４ｈｒ培養後の細胞生存率、（ｂ）は４８ｈｒ後の細胞生存率を示す。
試験結果より、前記添加物ＶＥを加えた場合、ビルベリーエキスのみの場合に較べていずれも細胞増殖抑制作用が増すことが明らかとなり、特にビルベリー濃度０．１μｇ／ｍｌ含有においてＶＥ添加の有無による効果が顕著であり、４８時間培養時における細胞生存率は２０％以下となっている。また、４８時間培養の場合の細胞生存率は２４時間培養の場合の細胞生存率の約５０％、すなわち約２倍の効果があることがわかった。
なお、ビルベリーエキスに対する添加剤ＶＥの添加による細胞増殖抑制作用への相乗効果は、他の添加剤（アミノ酸等）の添加、または他の添加剤（アミノ酸等）との併用添加による場合も期待できるものである。
また、本実施例２においては、添加量を固定したが、添加剤の多量添加による相乗効果アップも期待することができる。
FIG. 2 is a diagram showing the results of confirming a synergistic effect on various tumor-derived cancer cells by a mixed solution obtained by further adding the above-mentioned additives to bilberry extract in Example 2 of the present invention, and (a) is a culture for 24 hours. Later cell viability, (b) shows cell viability after 48 hr.
From the test results, it has been clarified that when the additive VE is added, the cell growth inhibitory effect is increased as compared with the case of only the bilberry extract. Is remarkable, and the cell survival rate after 48 hours of culture is 20% or less. Further, it was found that the cell viability in the case of 48 hours culture was about 50%, that is, about twice as effective as that in the case of 24 hours culture.
In addition, the synergistic effect to the cell growth inhibitory action by the addition of the additive VE to the bilberry extract can be expected by the addition of other additives (such as amino acids) or the combined use with other additives (such as amino acids). Is.
In Example 2, the addition amount is fixed, but a synergistic effect can be expected to be increased by adding a large amount of the additive.
本発明の実施例においては、対象がん細胞を大腸がん細胞（ＣＯＬＯ）、胃がん細胞（ＫＡＴＯ−III）、白血球系Ｔ細胞由来がん細胞（１９．１）、血球系単球由来がん細胞（Ｕ９３７）の場合としたが、上記のごとく、ビルベリーエキスおよび添加物による細胞増殖抑制効果はこれらに限られるものではなく、各種のがん細胞に対し有効な細胞増殖抑制作用を有する健康食品（飲料）として適用することができる。また、本発明に示したように、正常細胞に対しては増殖抑制を示さないことから、安全性の高い飲料である。 In the examples of the present invention, target cancer cells are colon cancer cells (COLO), gastric cancer cells (KATO-III), leukocyte T cell-derived cancer cells (19.1), blood cell monocyte-derived cancer. Although it was the case of cells (U937), as described above, the cell growth inhibitory effect of bilberry extract and additives is not limited to these, and a health food that has an effective cell growth inhibitory effect on various cancer cells It can be applied as (beverage). Moreover, as shown in this invention, since it does not show growth suppression with respect to a normal cell, it is a highly safe drink.
ＨＣＦ ヒト子宮頸管繊維芽細胞（正常細胞）、ＨＵＶ 正常内皮細胞、ＣＯＬＯ 大腸がん細胞、ＫＡＴＯ−III 胃印環がん細胞、Ｕ９３７ 単核球由来白血病細胞、Ａ３およびＩ９．１はＴリンパ球由来白血病細胞。
HCF human cervical fibroblasts (normal cells), HUV normal endothelial cells, COLO colon cancer cells, KATO-III gastrointestinal ring cancer cells, U937 mononuclear leukemia cells, A3 and I9.1 are T lymphocytes Derived leukemia cells.
Claims (5)
A first step of compressing and crushing bilberry fruit; a second step of extracting and standardizing from the compressed and crushed bilberry crushed material to produce a powdered bilberry extract containing 25% or more of anthocyanidins; and the bilberry of the powder Stirring and dissolving the extract in high-temperature water at 85 to 100 ° C. to form a bilberry extract (stock solution) containing 10,000 mg or more of bilberry extract per 100 ml, and a bilberry compound flavoring agent to the bilberry extract (stock solution) , Saccharides, acidulant and at least various vitamins, or / and amino acids as additives to form a bilberry beverage stock solution, and the bilberry beverage stock solution with 0.025 to 0.25 μg / ml of final anthocyanidin Having a fifth step of mixing and adding so as to contain a bilberry blended beverage Manufacturing method of bilberry blended food with tumor cell growth inhibiting effect of the symptoms.
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| JP2004357537A (en) * | 2003-06-03 | 2004-12-24 | Globe Science Inc | Bilberry-mixed drink and method for producing the same |
| JP2004357557A (en) * | 2003-06-04 | 2004-12-24 | Globe Science Inc | Bilberry-mixed food and method for producing the same |
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| JP2003277271A (en) * | 2002-03-26 | 2003-10-02 | Norioki Ko | Anticancer drug |
| JP2004357536A (en) * | 2003-06-03 | 2004-12-24 | Globe Science Inc | Method for producing bilberry undiluted liquid |
| JP2004357537A (en) * | 2003-06-03 | 2004-12-24 | Globe Science Inc | Bilberry-mixed drink and method for producing the same |
| JP2004357557A (en) * | 2003-06-04 | 2004-12-24 | Globe Science Inc | Bilberry-mixed food and method for producing the same |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2017119354A1 (en) * | 2016-01-08 | 2017-07-13 | アサヒビール株式会社 | Alcoholic beverage, method for manufacturing alcoholic beverage, and method for improving taste |
| JP2017121219A (en) * | 2016-01-08 | 2017-07-13 | アサヒビール株式会社 | Alcoholic beverage, method for producing alcoholic beverage, and method for improving taste |
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| JP4567508B2 (en) | 2010-10-20 |
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