JP4681246B2 - Immunostimulator - Google Patents
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- JP4681246B2 JP4681246B2 JP2004113771A JP2004113771A JP4681246B2 JP 4681246 B2 JP4681246 B2 JP 4681246B2 JP 2004113771 A JP2004113771 A JP 2004113771A JP 2004113771 A JP2004113771 A JP 2004113771A JP 4681246 B2 JP4681246 B2 JP 4681246B2
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- pilosa
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Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Plant Substances (AREA)
Description
本発明は、センダングサ属の植物、特にビデンス・ピローサまたはその成分を含有し、優れた免疫賦活作用を有する薬剤または飲食品の用途に関する。 The present invention relates to a use of a drug or a food or drink containing a plant of the genus Sendangusa, in particular, Bidence pirousa or a component thereof, and having an excellent immunostimulatory action.
近年、我が国における悪性新生物（ガン）による死亡者は全死亡者の３０％を占めており、ガンは我が国の死因第一位としてゆるぎないものになっている。一方、ここ数年アジア諸国で発生した重症急性呼吸器症候群（SARS：Severe Acute Respiratory Syndrome）や、鳥インフルエンザは、世界各地に感染を拡大して人々を恐怖と混乱に陥れてきた。様々な要因が我々の健康に対してマイナスに働くが、栄養の偏りや肉体的、精神的ストレス、老化と並んで最も重要なものが、自らが必要としない（微）生物による身体への侵襲である。ガンと感染症はこのような生物によって引き起こされる疾病であり、これらを自身から区別し、効率的かつ効果的に排除して自らを防御するのが免疫機能である。 In recent years, deaths from malignant neoplasms (cancer) in Japan accounted for 30% of all deaths, and cancer has become the leading cause of death in Japan. Meanwhile, Severe Acute Respiratory Syndrome (SARS) and bird flu that have occurred in Asian countries over the past few years have spread infection around the world, causing people to be terrified and confused. Various factors have a negative impact on our health, but the most important things along with nutritional bias, physical and mental stress, and aging are the ones that are not needed by the (micro) organisms that invade the body It is. Cancer and infectious diseases are diseases caused by such organisms, and their immune function is to protect them by distinguishing them from themselves and efficiently and effectively eliminating them.
ガンや感染症に対しては、抗ガン剤や抗菌剤・抗ウイルス剤等の抗生物質を使った対症療法が以前より広く行われているが、患者の持つ免疫機能を向上させればその治療効果がさらに高まると期待され、免疫賦活活性を有する薬剤の併用が試みられている。また、最近の健康ブームは、食生活の改善や特定の食品成分の力を借りることで「病気になりにくい体を作る」「病気になっても治りやすい体を作る」と言った意識を一般大衆に徐々に浸透させており、免疫機能を強化する医薬品だけでなく、このような機能性を有する飲食品の需要を高めてきた。 For cancer and infectious diseases, symptomatic treatment using antibiotics such as anticancer agents, antibacterial agents, and antiviral agents has been widely used, but if the patient's immune function is improved, the treatment The effect is expected to be further enhanced, and the combined use of drugs having immunostimulatory activity has been attempted. In addition, the recent health boom is generally based on the consciousness of "making a body that does not easily get sick" or "making a body that is easy to cure even if you get sick" by taking advantage of the improvement of eating habits and specific food ingredients It has been gradually permeating the masses and has increased the demand for foods and drinks with such functionality as well as pharmaceuticals that enhance immune function.
これまでに数多くの天然物について免疫賦活作用が研究され、効果が認められたいくつかの素材や抽出成分が医薬品や機能性食品の原料として実用化されている。しかしこれらの中には免疫賦活活性が不十分であったり、安全性が十分に確認されていないものも存在し、より高活性で安全性の高い天然素材の登場が望まれている。センダングサ属の植物は、熱帯から亜熱帯の地域に広く分布する野草である。古くからその葉、茎、根が抗菌作用や消炎鎮痛作用等の生理機能を有することが知られており、アフリカ大陸、中南米、中国・台湾など世界の各地で現在も民間薬として使われている。その適応症は、消化性潰瘍・胃痛・腹痛・下痢・便秘・腸内寄生虫等の胃腸疾患、咽頭炎・結核・赤痢・マラリア等の感染症、風疹・猩猴熱等の解熱、結膜炎・耳炎・腸炎等の炎症性疾患、リウマチ、糖尿病、肝臓病、外傷・火傷・毒蛇の噛傷などと非常に幅広い。センダングサ属の植物は食品の素材としても使われており、豊富な食経験を有するため安全性が高い天然素材であると考えられる。 So far, immunostimulatory action has been studied for many natural products, and several materials and extracted components that have been found effective have been put to practical use as raw materials for pharmaceuticals and functional foods. However, some of these have insufficient immunostimulatory activity or have not been sufficiently confirmed in safety, and the appearance of natural materials with higher activity and higher safety is desired. The plant of the genus Sendangusa is a wild grass widely distributed from tropical to subtropical regions. It has long been known that its leaves, stems, and roots have physiological functions such as antibacterial and anti-inflammatory analgesics, and it is still used as a folk medicine in various parts of the world such as the African continent, Latin America, China and Taiwan. . The indications are peptic ulcer, gastric pain, abdominal pain, diarrhea, constipation, intestinal parasites and other gastrointestinal diseases, pharyngitis, tuberculosis, dysentery, malaria and other infections, rubella, burning, etc., conjunctivitis, It has a very wide range of inflammatory diseases such as otitis / enteritis, rheumatism, diabetes, liver disease, trauma / burn / bite of poisonous snake. Plants of the genus Sendungusa are also used as food materials, and since they have abundant eating experience, they are considered to be natural materials with high safety.
ビデンス・ピローサは、学名をＢｉｄｅｎｓ ｐｉｌｏｓａ、別名タチアワユキセンダングサ（立泡雪栴檀草）、ムツウサ、シロノセンダングサ オオバナノセンダングサ等と呼び、我が国では宮古島において栽培されている。ビデンス・ピローサの機能性研究は我が国においても以前から継続して行われており、これまでに糖尿病、高コレステロール血症、炎症、アレルギー疾患等に対する改善効果が報告されている（特許文献１、特許文献２参照）。上記の通り、ビデンス・ピローサをはじめとするセンダングサ属の植物の免疫機能性としては、「抗炎症」と「抗アレルギー」があげられ、どちらかと言えば免疫抑制的な生理機能である。ビデンス・ピローサあるいはその他のセンダングサ属について、特定の免疫機能の強化を証明した知見は現時点では見あたらない。
以上のように社会問題となっているガンや感染症を予防・治療するにあたり、安全性が証明されている食品または食品に準ずるものから有効な素材を見いだす必要がある。本発明は、センダングサ属植物に見出された新規な生体調節機能を利用して、生体の免疫機能を高め、ガンや感染症の予防・治療に有効な薬剤または飲食品を提供することを目的とする。 As described above, in the prevention and treatment of cancer and infectious diseases that are social problems, it is necessary to find effective materials from foods that have been proven safe or equivalent to foods. An object of the present invention is to provide a drug or a food or drink that enhances the immune function of a living body by using a novel bioregulatory function found in a plant belonging to the genus Sendanga, and is effective in preventing or treating cancer and infectious diseases. And
本発明は上記目的を達成するためになされたもので、センダングサ属植物、特にビデンス・ピローサがこれまで知られていなかったような生理活性を有することを動物実験により確認して本発明を完成するに至った。すなわち、ビデンス・ピローサを始めとするセンダングサ属の植物を動物体に投与することで、Ｔリンパ球のインターフェロン−γ産生能、ＮＫ細胞活性、貪食細胞の貪食能を高めることができるため、本発明は生体内の白血球の機能を強化することにより、抗腫瘍、感染防御といった免疫賦活作用を発拝する医薬品・飲食品を提供する。 The present invention has been made to achieve the above-mentioned object, and completed the present invention by confirming by an animal experiment that a plant belonging to the genus Sendangusa, in particular, Bidence pilosa has a physiological activity that has not been known so far. It came to. That is, the administration of a plant of the genus Sendangusa such as Bidence Pilosa to an animal body can enhance the interferon-γ production ability of lymphocytes, the NK cell activity, and the phagocytic ability of phagocytic cells. Provides pharmaceuticals and foods that enhance the function of leukocytes in the body, thereby activating immunostimulatory effects such as anti-tumor and infection protection.
本発明によれば、センダングサ属植物、特にビデンス・ピローサまたはその抽出物を主成分として、免疫改善作用を有する医薬品や飲食品を容易に調製することができた。 ADVANTAGE OF THE INVENTION According to this invention, the medicine and food / beverage products which have an immune improvement effect | action can be prepared easily by making a Sendangusa genus plant, especially Bidence pillowa or its extract into a main component.
センダングサ属植物からの抽出に際しては、医薬品もしくは食品に使用可能な標品が得られることを条件としていかなる方法を使っても良く、得られた標品の純度は限定しない。また、適当な賦形剤と混合しても差し支えない。センダングサ属植物、特にビデンス・ピローサまたはその抽出物は、経口の医薬品として用いることができ、また食品素材と混合して飲食品とすることができる。性状としては固体状又は液体状を呈し、医薬品としては経口剤として錠剤、カプセル剤、顆粒剤、シロップ剤等の剤型をとる。 When extracting from the plant of the genus Sendungusa, any method may be used on the condition that a preparation that can be used for pharmaceuticals or foods is obtained, and the purity of the obtained preparation is not limited. Further, it may be mixed with an appropriate excipient. A plant of the genus Sendungusa, in particular, Bidence pirosa or an extract thereof, can be used as an oral medicine, and can be mixed with a food material to make a food or drink. The property is solid or liquid, and the pharmaceutical is in the form of tablets, capsules, granules, syrups and the like as oral preparations.
飲食品とする場合、これと混合する食品素材は固形物（粉状、薄片状、塊状など）、半固形物（ゼリー状、水飴状など）、もしくは液状物等のいずれであっても良い。飲食品１ｇあたりの植物体あるいはエキス含有量は、５〜２００ｍｇ（乾燥重量）であることが望ましい。 In the case of a food or drink, the food material to be mixed may be a solid (powder, flake, lump, etc.), a semi-solid (jelly, syrup, etc.), or a liquid. The content of the plant or extract per gram of food or drink is preferably 5 to 200 mg (dry weight).
本発明のセンダングサ属植物、特にビデンス・ピローサまたはその成分を含有する医薬品及び飲食品は、白血球の機能を高めるため、ガン・感染症をはじめとして、免疫力低下や免疫異常の関与する様々な疾患の予防及び治療に有効なものである。
以下、本発明を実施例によってさらに具体的に説明するが、本発明はこれに限定されるものではない。
The plant of the genus Sendangusa of the present invention, in particular, pharmaceuticals and foods and drinks containing Bidence pirousa or components thereof, enhances the function of leukocytes, and thus various diseases involving immunity reduction and immune abnormalities including cancer and infectious diseases It is effective for prevention and treatment.
Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.
（ビデンス・ピローサ抽出物の調製）
ビデンス・ピローサ全草の乾燥物１００ｇを細かく粉砕した後、２Ｌの水に懸濁して９０〜１００℃で１時間抽出処理を行った。濾過により上清を分取して凍結乾燥を行い、最終的に６ｇのビデンス・ピローサ熱水抽出物を得た。
(Preparation of Bidence Pilosa extract)
After 100 g of dried Bidence Pirosa whole material was finely pulverized, it was suspended in 2 L of water and extracted at 90-100 ° C. for 1 hour. The supernatant was collected by filtration and lyophilized to finally obtain 6 g of a Bidence Pilosa hot water extract.
（錠剤、カプセル剤）
ビデンス・ピローサ熱水抽出物 １０・０ｇ
乳糖 ７５．０ｇ
ステアリン酸マグネシウム １５．５ｇ
合 計 １００．０ｇ
上記の各重量部を均一に混合し、常法に従って錠剤、カプセル剤とした。
(Tablets and capsules)
Bidence Pilosa hot water extract 10.0g
Lactose 75.0g
Magnesium stearate 15.5g
Total 100.0g
The above respective parts by weight were uniformly mixed, and tablets and capsules were prepared according to a conventional method.
（散剤、顆粒剤）
ビデンス・ピローサ熱水抽出物 ２０．０ｇ
澱粉 ３０・０ｇ
乳糖 ５０．０ｇ
合計 １００．０ｇ
上記の各重量部を均一に混合し、常法に従って散剤、顆粒剤とした。
(Powder, granule)
Bidence Pilosa hot water extract 20.0g
Starch 30.0g
Lactose 50.0g
Total 100.0g
Each said weight part was mixed uniformly, and it was set as the powder and the granule according to the conventional method.
（飴）
ショ糖 ２０．０ｇ
水飴（７５％固形分） ７０．０ｇ
水 ９．５ｇ
着色料 ０．４５ｇ
香 料 ０．０４５ｇ
ビデンス・ピローサ熱水抽出物 ０．００５ｇ
合 計 １００．０ｇ
上記の各重量部の各成分を用い、常法に従って飴とした。
(candy)
Sucrose 20.0g
Chickenpox (75% solids) 70.0g
9.5g of water
Coloring material 0.45g
Perfume 0.045g
Bidence Pilosa hot water extract 0.005g
Total 100.0g
Using each component of each of the above parts by weight, it was made into a candy according to a conventional method.
（ジュース）
濃縮ミカン果汁 １５．０ｇ
果 糖 ５．０ｇ
クエン酸 ０．２ｇ
香 料 ０．１ｇ
色 素 ０．１５ｇ
アスコルビン酸ナトリウム ０．０４８ｇ
ビデンス・ピローサ熱水抽出物 ０．００２ｇ
水 ７９．５ｇ
合 計
１００．０ｇ
上記の各重量部の各成分を用い、常法に従ってジュースとした。
(juice)
Concentrated tangerine juice 15.0 g
Fructose 5.0g
Citric acid 0.2g
Fragrance 0.1g
0.15 g of color
Sodium ascorbate 0.048g
Bidence Pilosa hot water extract 0.002g
79.5g of water
total
100.0g
Using each component of the above-mentioned parts by weight, juice was prepared according to a conventional method.
（クッキー）
薄力粉 ３２．O g
全 卵 １６．O g
バター １６．O g
砂糖 ２５．０ｇ
水 １０．８ｇ
ベーキングパウダー ０．１９８ｇ
ビデンス・ピローサ熱水抽出物 ０．００２ｇ
合 計
１００．０ｇ
上記の各重量部の各成分を用い、常法に従ってクッキーとした。
(cookie)
Soft flour 32. O g
Whole egg 16. O g
Butter 16. O g
25.0g sugar
10.8 g of water
Baking powder 0.198g
Bidence Pilosa hot water extract 0.002g
total
100.0g
Using each component of the above-mentioned parts by weight, a cookie was prepared according to a conventional method.
（ビデンス・ピローサ熱水抽出物のＮＫ細胞活性化作用）
６週齢の雄性ＢＡＬＢ／Ｃマウスを１週間予備飼育した後、各群６匹として蒸留水または実施例１記載のビデンス・ピローサ熱水抽出物水溶液（固形分０．３％）を１０ｍｌ／ｋｇ／日の用量で１週間経口投与した。その後牌臓細胞を採取し、ＹＡＣ−１と５０：１の割合で混合し、３７℃、５％ＣＯ２条件下で４時間インキュべートした。ＹＡＣ−１の致死率をＮＫ細胞活性の指標としてフローサイトメトリーにて解析したところ、ビデンス・ピローサ熱水抽出物投与群は対照群と比して有意（ｐ＜０．０１）にＮＫ活性が増加した。
(Activation of NK cells by Bidence Pilosa hot water extract)
Six weeks old male BALB / C mice were preliminarily raised for one week, and then each group consisted of 6 mice with 10 ml / kg of distilled water or the aqueous solution of the extract of the Bidence / Pirosa hot water described in Example 1 (solid content 0.3%). Per day for 1 week. Thereafter, spleen cells were collected, mixed with YAC-1 at a ratio of 50: 1, and incubated at 37 ° C. under 5% CO 2 for 4 hours. When the lethality rate of YAC-1 was analyzed by flow cytometry as an index of NK cell activity, the NK activity was significantly (p <0.01) higher in the Bidence-Pirosa hot water extract administration group than in the control group. Increased.
表１
ＮＫ細胞活性（％）
投与群 平均値 標準誤差
対照 27.12 2.53
抽出物 41.43＊＊ 2.88
（＊＊：有意確率ｐ＜0.01）
Table 1
NK cell activity (%)
Treatment group mean Standard error
Control 27.12 2.53
Extract 41.43 ** 2.88
(**: Significance probability p <0.01)
（ビデンス・ピローサ熱水抽出物のＩＦＮ−γ産生亢進作用）
６週齢の雄性ＢＡＬＢ／Ｃマウスを１週間予備飼育した後、各群６匹として蒸留水またはビデンス・ピローサ熱水抽出物水溶液（固形分０．３％）を１０ｍｌ／ｋｇ／日の用量で１週間経口投与した。その後牌臓細胞を採取し、Ｃｏｎ Ａ添加培地で２日間培養し培養上清中のＩＦＮ−γ産生量をエライザ法により測定したところ、ビデンス・ピローサ熱水抽出物投与群は対照群と比して有意（ｐ＜０．０５）に産生能を亢進することを確認した。
表２
培養上清中ＩＦＮ−γ濃度（ng／ml）
投与群 平均値 標準誤差
対照 8.53 0.77
抽出物 14.26＊ 2.65
（＊：有意確率ｐ＜0.05）
(IFN-γ production enhancing action of Bidence Pilosa hot water extract)
Six weeks old male BALB / C mice were preliminarily raised for one week, and then each group had 6 mice with distilled water or a Bidence Pilosa hot water extract aqueous solution (solid content 0.3%) at a dose of 10 ml / kg / day. Orally administered for 1 week. Thereafter, the spleen cells were collected, cultured for 2 days in a medium supplemented with Con A, and the amount of IFN-γ produced in the culture supernatant was measured by the Eliza method. The group administered with the Vidence-Pirosa hot water extract was compared with the control group. It was confirmed that the productivity was significantly (p <0.05) enhanced.
Table 2
IFN-γ concentration in culture supernatant (ng / ml)
Treatment group mean Standard error
Control 8.53 0.77
Extract 14.26 * 2.65
(*: Significance probability p <0.05)
（ビデンス・ピローサ熱水抽出物の顆粒球貪食能克進作用）
６週齢の雄性ＢＡＬＢ／Ｃマウスを１週間予備飼育した後、各群６匹として蒸留水またはビデンス・ピローサ熱水抽出物水溶液（固形分０．３％）を１０ｍｌ／ｋｇ／日の用量で１週間経口投与した。その後、眼窩採血を行い蛍光標識ラテックス粒子取込み法にて末梢血顆粒球の貪食能（取込まれたラテックスビーズ数／細胞）をフローサイトメトリーにて解析したところ、ビデンス・ピローサ熱水抽出物投与群は対照群と比して有意（ｐ＜０．０５）に貪食能が亢進した。
表３
貪食能（％）
投与群 平均値 標準誤差
対照 1.81 0.03
抽出物 1.90＊ 0.05
（＊：有意確率Ｐ＜0.05）
(Bidence Pilosa hot water extract granulocyte phagocytosis action)
Six weeks old male BALB / C mice were preliminarily raised for one week, and then each group had 6 mice with distilled water or a Bidence Pilosa hot water extract aqueous solution (solid content 0.3%) at a dose of 10 ml / kg / day. Orally administered for 1 week. Then, blood was collected from the orbit, and the phagocytic ability (number of latex beads incorporated / cell) of peripheral blood granulocytes was analyzed by flow cytometry using the fluorescent-labeled latex particle uptake method. The group had significantly enhanced phagocytic ability (p <0.05) compared to the control group.
Table 3
貪 Food ability (%)
Treatment group mean Standard error
Control 1.81 0.03
Extract 1.90 * 0.05
(*: Significance probability P <0.05)
（ビデンス・ピローサ熱水抽出物の癌細胞増殖抑制作用）
６週齢の雄性ＢＡＬＢ／Ｃマウスを１週間予備飼育した後、各群８匹として蒸留水またはビデンス・ピローサ熱水抽出物水溶液（固形分０．３％）を１０ｍｌ／ｋｇ／日の用量で４週間経口投与した。経口投与開始１週間後、エーリッヒ癌細胞をマウスの左大腿部に筋肉内投与し、試験終了時に癌細胞投与部位の重量を測定した。ビデンス・ピローサ熱水抽出エキス投与群は対照群と比して癌細胞の増殖を抑制する傾向を示した。
表４
腫瘍重量（ｇ）
投与群 平均値 標準誤差
対照 4.32 1.54
抽出物 3.00 1.28
(The cancer cell growth inhibitory effect of the Bidence Pilosa hot water extract)
Six weeks old male BALB / C mice were preliminarily raised for one week, and then each group had 8 animals with distilled water or an aqueous solution of Bidence Pilosa hot water extract (solid content 0.3%) at a dose of 10 ml / kg / day. Orally administered for 4 weeks. One week after the start of oral administration, Erich cancer cells were intramuscularly administered to the left thigh of the mouse, and the weight of the cancer cell administration site was measured at the end of the test. The Bidence Pilosa hot water extract extract administration group showed a tendency to suppress the growth of cancer cells compared to the control group.
Table 4
Tumor weight (g)
Treatment group mean Standard error
Control 4.32 1.54
Extract 3.00 1.28
Claims (3)
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| JP2003160486A (en) * | 2001-09-17 | 2003-06-03 | Lion Corp | Oral hair grower and food/drink containing the same |
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| JP2001178390A (en) * | 1999-12-28 | 2001-07-03 | Musashino Meneki Kenkyusho:Kk | Method of processing spanish needle |
| JP2003160486A (en) * | 2001-09-17 | 2003-06-03 | Lion Corp | Oral hair grower and food/drink containing the same |
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