JPH07258104A - Cancer metastasis suppressing agent - Google Patents
Cancer metastasis suppressing agentInfo
- Publication number
- JPH07258104A JPH07258104A JP6072819A JP7281994A JPH07258104A JP H07258104 A JPH07258104 A JP H07258104A JP 6072819 A JP6072819 A JP 6072819A JP 7281994 A JP7281994 A JP 7281994A JP H07258104 A JPH07258104 A JP H07258104A
- Authority
- JP
- Japan
- Prior art keywords
- cancer metastasis
- pts
- extract
- suppressing agent
- metastasis suppressing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- Medicines Containing Plant Substances (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は桂枝、芍薬、大棗、生姜
及び甘草、又はそれらの抽出物を有効成分として含有す
る癌転移抑制剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cancer metastasis inhibitor containing, as an active ingredient, laurel, peony, oju, ginger and licorice, or extracts thereof.
【０００２】[0002]
【従来の技術】転移は、様々な癌患者において誘発され
る。この為、原発巣が最新の化学療法で治療された後で
も最終的に転移・再発により死亡するケースが非常に多
く、転移を克服する医薬の開発が望まれている。Metastasis is induced in a variety of cancer patients. Therefore, even after the primary tumor is treated with the latest chemotherapy, there are many cases where death eventually occurs due to metastasis / recurrence, and development of a drug that overcomes metastasis is desired.
【０００３】一方、桂枝、芍薬、大棗、生姜及び甘草を
構成生薬とする桂枝加桂湯は、感冒、一種のめまいや耳
鳴りなどなどの症状改善に用いられていたが、癌疾患の
治療に使用された例はない。[0003] On the other hand, Keishikakeito, whose constituent crude drugs are keishi, peony, oju, ginger and licorice, has been used for amelioration of symptoms such as colds, dizziness and tinnitus, but it is not a cancer disease. It has never been used for treatment.
【０００４】[0004]
【発明が解決しようとする課題】本発明は、混合生薬又
はその抽出物を有効成分とし、安全性の高く、癌転移の
克服に有用な医薬を提供することを目的とする。SUMMARY OF THE INVENTION It is an object of the present invention to provide a medicine which contains a mixed crude drug or an extract thereof as an active ingredient and has high safety and which is useful for overcoming cancer metastasis.
【０００５】[0005]
【課題を解決するための手段】本発明は、桂枝、芍薬、
大棗、生姜及び甘草、又はそれらの抽出物を有効成分と
して含有する癌転移抑制剤である。Means for Solving the Problems The present invention is directed to katsura, peony,
It is a cancer metastasis inhibitor containing, as an active ingredient, large jujuba, ginger, licorice, or an extract thereof.
【０００６】本発明の有効成分における各生薬の配合割
合は、好ましくは桂枝２．０〜９．０重量部、芍薬２．
０〜６．０重量部、大棗２．０〜６．０重量部、生姜
０．５〜６．０重量部及び甘草０．５〜４．０重量部で
ある。The mixing ratio of each crude drug in the active ingredient of the present invention is preferably 2.0 to 9.0 parts by weight of kelp, peony root 2.
It is 0 to 6.0 parts by weight, Oomu 2.0 to 6.0 parts by weight, ginger 0.5 to 6.0 parts by weight, and licorice 0.5 to 4.0 parts by weight.
【０００７】かかる好ましい配合割合の各生薬からなる
漢方処方としては、例えば桂枝加桂湯が挙げられる。桂
枝加桂湯の処方は、漢方処方の古典（金匱要略等）に記
載されており、若干の差異があるが、各生薬の配合範囲
は、一般に次の通りである。 ［桂枝加桂湯］ 桂枝：４．０〜７．０重量部 芍薬：４．０重量部 大棗：４．０重量部 生姜：１．５〜４．０
重量部 甘草：２．０重量部[0007] Examples of Kampo prescriptions comprising the respective crude drugs in such preferable mixing ratios include Keishikakeito. The prescription of Keishikakeito is described in the classical Chinese herbal formula (Kinbyo, etc.) and there are some differences, but the range of each herbal medicine is generally as follows. [Keishikakeito] Keishi: 4.0 to 7.0 parts by weight Peony: 4.0 parts by weight Ojujumu: 4.0 parts by weight Ginger: 1.5 to 4.0 parts
Parts by weight Licorice: 2.0 parts by weight
【０００８】上記生薬の抽出物としては、各種水系溶剤
抽出物が挙げられるが、水抽出物を用いることが好まし
い。具体的な、抽出物の調製例としては上記配合の生薬
混合物を１０〜２０倍量の熱水で抽出し、得られた抽出
液を濾過する方法が挙げられる。この抽出物は必要に応
じて乾燥させ、乾燥粉末として用いることができる。Examples of the crude drug extract include various aqueous solvent extracts, and it is preferable to use a water extract. As a specific example of preparation of the extract, there is a method of extracting the crude drug mixture having the above composition with 10 to 20 times the amount of hot water and filtering the obtained extract. This extract can be dried if necessary and used as a dry powder.
【０００９】本発明の有効成分の具体例を示して、詳細
に説明する。Specific examples of the active ingredients of the present invention will be shown and described in detail.
【００１０】具体例１ 桂枝６．０ｇ、芍薬４．０ｇ、大棗４．０ｇ、生姜１．
５ｇ及び甘草２．０ｇの混合生薬（桂枝加桂湯：１７．
５ｇ）に約１８０ｇの精製水を加え、１００°Ｃで１時
間加熱抽出した。得られた抽出液を濾過後、スプレード
ライして４．７ｇの乾燥エキス粉末を得た。SPECIFIC EXAMPLE 1 6.0 g of laurel, 4.0 g of peony, 4.0 g of oju, ginger 1.
5 g and licorice 2.0 g mixed crude drug (Keishikakeito: 17.
About 5Og of purified water was added to 5g) and the mixture was extracted by heating at 100 ° C for 1 hour. The obtained extract was filtered and then spray-dried to obtain 4.7 g of dry extract powder.
【００１１】具体例２ 桂枝６００ｇ、芍薬４００ｇ、大棗４００ｇ、生姜１５
０ｇ及び甘草２００ｇの混合生薬（桂枝加附子湯：１．
７５ｋｇ）に２０ｌの精製水を加え、加熱し、１００°
Ｃになってから１時間抽出した。得られた抽出液を遠心
分離機にかけ、残渣を分離して溶液を得た。Concrete Example 2 600 g of edible cabbage, 400 g of peony, 400 g of oju, ginger 15
0 g and 200 g of licorice mixed crude drug (Keishikabushito: 1.
75 kg) with 20 liters of purified water and heated to 100 °
It extracted for 1 hour after becoming C. The obtained extract was centrifuged and the residue was separated to obtain a solution.
【００１２】この溶液を０．３μｍのメンブランフィル
ター（東洋濾紙社製）により無菌清澄濾過した。得られ
た濾液をダイアフィルターＧ−１０Ｔ（バイオエンジニ
アリング社製：分画分子量１００００）を用いて限外濾
過した。この限外濾過は、内容積２．０ｌの容器の下面
に直径１５２ｍｍの膜をセットし、圧力３ｋｇ／ｃｍ2
で行い、容器内の液が濃縮されるにつれ精製水を添加す
るというように実施した。この結果、限外濾過液を得
た。This solution was subjected to aseptic clarification filtration with a 0.3 μm membrane filter (manufactured by Toyo Roshi Kaisha, Ltd.). The obtained filtrate was ultrafiltered using a diafilter G-10T (manufactured by Bio Engineering Co., Ltd .: molecular weight cut off 10,000). For this ultrafiltration, a membrane with a diameter of 152 mm was set on the lower surface of a container with an internal volume of 2.0 l and the pressure was 3 kg / cm 2.
Then, purified water was added as the liquid in the container was concentrated. As a result, an ultrafiltrate was obtained.
【００１３】次に、本発明の有効成分が顕著な癌転移抑
制効果を有することについて、実験例に挙げて説明す
る。Next, the fact that the active ingredient of the present invention has a remarkable cancer metastasis inhibitory effect will be described with reference to experimental examples.
【００１４】実験例 メラノーマ細胞をマウスに移植した１４日後に、メラノ
ーマ細胞の肺転移巣数を比較し、本発明の有効成分の効
果を検討した。その詳細は、以下の通りである。Experimental Example 14 days after the transplantation of melanoma cells into mice, the number of lung metastases of melanoma cells was compared to examine the effect of the active ingredient of the present invention. The details are as follows.
【００１５】８週齢Ｃ５７ＢＬ／６雄マウスにイン・ビ
トロで継代したＢ１６Ｆ１０（高転移性株）メラノーマ
細胞（１〜２×１０5個）をマウス（１群１０匹）の尾
静脈より移植した。移植１日後より隔日４回（１、３、
５、７日）胃ゾンテを用いて具体例１で得られた本発明
の有効成分（８０ｍｇ／ｋｇ）を経口投与した。また、
生理食塩水を経口投与されたマウスを対照群とした。転
移巣の定量は、経日的（主として１４日後）に肺を摘
出、ホルマリンで固定した後、黒色に見える転移巣を解
剖顕微鏡下で計数した。結果を表１に示す。8-week-old C57BL / 6 male mice were transplanted with B16F10 (highly metastatic strain) melanoma cells (1 to 2 × 10 5 cells) passaged in vitro from the tail vein of mice (10 mice per group). did. 1 day after transplantation 4 times every other day (1, 3,
(5 and 7 days) The active ingredient of the present invention (80 mg / kg) obtained in Example 1 was orally administered using a stomach stomach. Also,
Mice orally administered with physiological saline served as a control group. To quantify the metastatic foci, the lungs were excised daily (mainly 14 days later) and fixed with formalin, and then the metastatic foci that appeared black were counted under a dissecting microscope. The results are shown in Table 1.
【００１６】表１ Table 1
【００１７】上述の結果より明らかように、本発明の有
効成分投与群は、対照群（生理食塩水投与）に比べて７
４％の転移が抑制され、顕著な癌転移抑制効果を有する
ことが確認された。従って、様々な癌患者において誘発
される癌転移の治療に有用な医薬であることが確認され
た。As is clear from the above-mentioned results, the active ingredient-administered group of the present invention was compared with the control group (administered with physiological saline) by 7%.
It was confirmed that 4% of metastasis was suppressed and that it had a remarkable cancer metastasis suppressing effect. Therefore, it was confirmed that the drug is useful for treating cancer metastasis induced in various cancer patients.
【００１８】次に、本発明の有効成分である桂枝加桂湯
の経口投与での急性毒性試験をｄｄＹ系雄性マウス及び
ウィスター系雄性ラットを用いて行ったところ、具体例
１で得られた乾燥エキスは、１５ｇ／ｋｇ（限界投与）
においても、死亡例の発現は見られなかった。このよう
に、本発明は、極めて毒性の低いものである。Next, an acute toxicity test of oral administration of Keishikakeito, which is an active ingredient of the present invention, was conducted using male ddY mice and male Wistar rats, and it was obtained in Example 1. 15 g / kg of dried extract (limit dose)
Also, no occurrence of death was observed. As described above, the present invention has extremely low toxicity.
【００１９】次に、本発明の有効成分の投与量及び製剤
化について説明する。Next, the dose and formulation of the active ingredient of the present invention will be explained.
【００２０】本発明の有効成分の投与形態としては、特
に限定がなく、必要に応じ適宜選択して使用され、錠
剤、カプセル剤、顆粒剤、細粒剤、散剤等の経口剤、注
射剤、坐剤等の非経口剤が挙げられる。The dosage form of the active ingredient of the present invention is not particularly limited and may be appropriately selected and used as necessary. Oral preparations such as tablets, capsules, granules, fine granules and powders, injection preparations, Parenteral agents such as suppositories may be mentioned.
【００２１】所期の効果を発揮するためには、患者の年
令、体重、疾患の程度により異なるが、通常成人で本発
明の有効成分の重量として２〜１５ｇを、１日数回に分
けての服用が適当と思われる。In order to exert the intended effect, it depends on the age, body weight, and degree of disease of the patient, but usually 2 to 15 g of the active ingredient of the present invention is divided into several times a day in adults. Seems to be appropriate.
【００２２】本発明の有効成分は、錠剤、カプセル剤、
顆粒剤等の経口剤は、例えばデンプン、乳糖、白糖、マ
ンニット、カルボキシメチルセルロース、コーンスター
チ、無機塩類等を用いて常法に従って製造される。The active ingredient of the present invention includes tablets, capsules,
Oral preparations such as granules are produced by a conventional method using starch, lactose, sucrose, mannitol, carboxymethyl cellulose, corn starch, inorganic salts and the like.
【００２３】この種の製剤には、適宜前記賦形剤の他
に、結合剤、崩壊剤、界面活性剤、滑沢剤、流動性促進
剤、矯味剤、着色剤、香料等を使用することができる。
それぞれの具体例は以下に示すごとくである。In this type of formulation, a binder, a disintegrant, a surfactant, a lubricant, a fluidity enhancer, a flavoring agent, a coloring agent, a flavoring agent, etc. may be appropriately used in addition to the above-mentioned excipients. You can
Specific examples of each are as shown below.
【００２４】［結合剤］デンプン、デキストリン、アラ
ビアゴム末、ゼラチン、ヒドロキシプロピルスターチ、
メチルセルロース、カルボキシメチルセルロースナトリ
ウム、ヒドロキシプロピルセルロース、結晶セルロー
ス、エチルセルロース、ポリビニルピロリドン、マクロ
ゴール。[Binder] Starch, dextrin, gum arabic powder, gelatin, hydroxypropyl starch,
Methyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, crystalline cellulose, ethyl cellulose, polyvinylpyrrolidone, macrogol.
【００２５】［崩壊剤］デンプン、ヒドロキシプロピル
スターチ、カルボキシメチルセルロースナトリウム、カ
ルボキシメチルセルロースカルシウム、カルボキシメチ
ルセルロース、低置換ヒドロキシプロピルセルロース。[Disintegrant] Starch, hydroxypropyl starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, low-substituted hydroxypropyl cellulose.
【００２６】［界面活性剤］ラウリル硫酸ナトリウム、
大豆レシチン、ショ糖脂肪酸エステル、ポリソルベート
８０。[Surfactant] sodium lauryl sulfate,
Soy lecithin, sucrose fatty acid ester, polysorbate 80.
【００２７】［滑沢剤］タルク、ロウ類、水素添加植物
油、ショ糖脂肪酸エステル、ステアリン酸マグネシウ
ム、ステアリン酸カルシウム、ステアリン酸アルミニウ
ム、ポリエチレングリコール。[Lubricant] Talc, wax, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, polyethylene glycol.
【００２８】［流動性促進剤］軽質無水ケイ酸、乾燥水
酸化アルミニウムゲル、合成ケイ酸アルミニウム、ケイ
酸マグネシウム。[Fluidity promoter] Light anhydrous silicic acid, dried aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate.
【００２９】また、本発明の有効成分は、懸濁剤、エマ
ルジョン剤、シロップ剤、エリキシル剤としても投与す
ることができ、これらの各種剤形には、矯味矯臭剤、着
色剤を含有してもよい。The active ingredient of the present invention can also be administered as a suspension, emulsion, syrup or elixir, and these various dosage forms contain a flavoring agent and a coloring agent. Good.
【００３０】一方、非経口剤は常法に従って製造され、
希釈剤として一般に注射用蒸留水、生理食塩水、ブドウ
糖水溶液、注射用植物油、ゴマ油、ラッカセイ油、ダイ
ズ油、トウモロコシ油、プロピレングリコール、ポリエ
チレングリコール等を用いることができる。さらに必要
に応じて、殺菌剤、防腐剤、安定剤を加えてもよい。ま
た、この非経口剤は安定性の点から、バイアル等に充填
後冷凍し、通常の凍結乾燥技術により水分を除去し、使
用直前に凍結乾燥物から液剤を再調製することもでき
る。さらに、必要に応じて適宜、等張化剤、安定剤、防
腐剤、無痛化剤等を加えても良い。On the other hand, parenteral preparations are manufactured by a conventional method,
Generally, distilled water for injection, physiological saline, aqueous glucose solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil, corn oil, propylene glycol, polyethylene glycol and the like can be used as the diluent. Further, if necessary, a bactericide, a preservative, and a stabilizer may be added. Further, from the viewpoint of stability, this parenteral preparation may be filled in a vial or the like and then frozen, the water content may be removed by a usual freeze-drying technique, and a liquid preparation may be re-prepared from the freeze-dried product immediately before use. Further, an isotonicity agent, a stabilizer, a preservative, a soothing agent and the like may be added as needed.
【００３１】以下、実施例を示して本発明を更に詳細な
説明をするが、本発明はこれにより何ら制限されるもの
ではない。Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
【００３２】実施例１ 具体例１で得られた桂枝加桂湯２００ｇを乳糖８９ｇお
よびステアリン酸マグネシウム１ｇと混合し、この混合
物を単発式打錠機にて打錠して、直径２０ｍｍ、重量約
２．３ｇのスラッグ錠を作り、これを、オシレーターに
て粉砕し、整粒し、識別して２０〜５０メッシュの粒子
の良好な顆粒剤を得た。この顆粒剤は、症状に合わせて
１回量０．５〜４．５ｇ（桂枝加桂湯の乾燥エキス重量
として０．３４〜３．１０ｇに相当）を１日３回服用す
る。Example 1 200 g of Keishikakeito obtained in Example 1 was mixed with 89 g of lactose and 1 g of magnesium stearate, and this mixture was tabletted with a single-shot tableting machine to give a diameter of 20 mm and a weight. Approximately 2.3 g of slug tablet was prepared, and this was crushed by an oscillator, sized, and identified to obtain a good granule having particles of 20 to 50 mesh. This granule is taken at a dose of 0.5 to 4.5 g (corresponding to a dry extract weight of Keishikakeito of 0.34 to 3.10 g) three times a day according to the symptoms.
【００３３】実施例２ 具体例１で得られた桂枝加桂湯２００ｇを微結晶セルロ
ース２０ｇおよびステアリン酸マグネシウム５ｇと混合
し、この混合物を単発式打錠機にて打錠して、直径７ｍ
ｍ，重量２２５ｍｇの錠剤を製造した。本錠剤１錠中に
はの桂枝加桂湯乾燥エキスを２００ｍｇ含有する。本錠
剤は、症状に合わせて１日量２〜１６錠を１日３回服用
する。Example 2 200 g of Keishikakeito obtained in Example 1 was mixed with 20 g of microcrystalline cellulose and 5 g of magnesium stearate, and this mixture was tabletted with a single-shot tableting machine to give a diameter of 7 m.
m, weight 225 mg tablets were produced. One tablet of this tablet contains 200 mg of dried extract of Keishikakeito. This tablet is taken at a daily dose of 2 to 16 tablets 3 times a day according to the symptoms.
【００３４】[0034]
【発明の効果】本発明によれば、混合生薬又はその抽出
物を有効成分とし、安全性の高く、顕著な癌転移抑制効
果を有する医薬を提供することができる。 以上INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a medicine which contains a mixed crude drug or an extract thereof as an active ingredient and is highly safe and has a remarkable cancer metastasis suppressing effect. that's all
Claims (2)
その抽出物を有効成分として含有する癌転移抑制剤。1. A cancer metastasis inhibitor containing, as an active ingredient, katsura, peony, oju, ginger and licorice, or an extract thereof.
である請求項２記載の癌転移抑制剤。2. The cancer metastasis inhibitor according to claim 2, wherein the active ingredient is Keishikakeito or an extract thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6072819A JPH07258104A (en) | 1994-03-18 | 1994-03-18 | Cancer metastasis suppressing agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6072819A JPH07258104A (en) | 1994-03-18 | 1994-03-18 | Cancer metastasis suppressing agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07258104A true JPH07258104A (en) | 1995-10-09 |
Family
ID=13500412
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6072819A Pending JPH07258104A (en) | 1994-03-18 | 1994-03-18 | Cancer metastasis suppressing agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07258104A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100559489B1 (en) * | 2003-08-05 | 2006-03-10 | 한국생명공학연구원 | Composition comprising ZiZyphy Fructus extract and compounds isolated from above extract for anti-cancer and anti-metastatic |
| US7081259B2 (en) * | 2001-02-20 | 2006-07-25 | Healthy & Happy Co., Ltd. | Herbal, extract having therapeutic activity on injuries, and pharmaceutical composition and health food containing the same |
| JP2013079215A (en) * | 2011-10-04 | 2013-05-02 | Nihon Univ | Invasion inhibitor for oral cancer cell |
-
1994
- 1994-03-18 JP JP6072819A patent/JPH07258104A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7081259B2 (en) * | 2001-02-20 | 2006-07-25 | Healthy & Happy Co., Ltd. | Herbal, extract having therapeutic activity on injuries, and pharmaceutical composition and health food containing the same |
| KR100559489B1 (en) * | 2003-08-05 | 2006-03-10 | 한국생명공학연구원 | Composition comprising ZiZyphy Fructus extract and compounds isolated from above extract for anti-cancer and anti-metastatic |
| JP2013079215A (en) * | 2011-10-04 | 2013-05-02 | Nihon Univ | Invasion inhibitor for oral cancer cell |
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