JPH052684B2 - - Google Patents
Info
- Publication number
- JPH052684B2 JPH052684B2 JP58190824A JP19082483A JPH052684B2 JP H052684 B2 JPH052684 B2 JP H052684B2 JP 58190824 A JP58190824 A JP 58190824A JP 19082483 A JP19082483 A JP 19082483A JP H052684 B2 JPH052684 B2 JP H052684B2
- Authority
- JP
- Japan
- Prior art keywords
- water
- molecular weight
- ether
- polysaccharide
- vistaria
- 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.)
- Expired - Lifetime
Links
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 239000000126 substance Substances 0.000 claims description 22
- 150000004676 glycans Chemical class 0.000 claims description 20
- 229920001282 polysaccharide Polymers 0.000 claims description 20
- 239000005017 polysaccharide Substances 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000000108 ultra-filtration Methods 0.000 claims description 11
- 241000196324 Embryophyta Species 0.000 claims description 10
- 241000220485 Fabaceae Species 0.000 claims description 10
- 235000021374 legumes Nutrition 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 239000003125 aqueous solvent Substances 0.000 claims description 4
- 239000000470 constituent Substances 0.000 claims description 4
- 238000000921 elemental analysis Methods 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 4
- 235000000346 sugar Nutrition 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 238000000502 dialysis Methods 0.000 claims description 3
- 150000008163 sugars Chemical class 0.000 claims description 3
- 239000000385 dialysis solution Substances 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 238000000638 solvent extraction Methods 0.000 claims 1
- 239000000843 powder Substances 0.000 description 24
- 230000000259 anti-tumor effect Effects 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 239000006188 syrup Substances 0.000 description 5
- 235000020357 syrup Nutrition 0.000 description 5
- 206010003445 Ascites Diseases 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000007863 gel particle Substances 0.000 description 3
- 238000005227 gel permeation chromatography Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- -1 mannitrate Polymers 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- KSSNXJHPEFVKHY-UHFFFAOYSA-N phenol;hydrate Chemical compound O.OC1=CC=CC=C1 KSSNXJHPEFVKHY-UHFFFAOYSA-N 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003809 water extraction Methods 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011552 falling film Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229940124600 folk medicine Drugs 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Description
本発明は抗腫瘍性を有する新規な多糖体および
その製造方法、さらには、それを有効成分として
含有する抗腫瘍剤に関する。
マメ科ビスタリア属に属する植物の地上部に発
生する塊状瘤は、フジコブ、フジノコブあるいは
藤瘤と呼ばれ、古来から民間薬として健胃薬に用
いられてきた生薬である。
本発明者等は、種々の生薬の抗腫瘍作用につい
てのスクリーニングテストを行つた結果、マメ科
ビスタリア属に属する植物の地上部に発生する塊
状瘤が動物の実験腫瘍に対して、すぐれた抗腫瘍
作用を示すことを明らかにした。この事実に着目
し、マメ科ビスタリア属に属する植物の地上部に
発生する塊状瘤から有効成分の分離を行つたとこ
ろ、新規な多糖体を分離精製することに成功し、
該多糖体が抗腫瘍作用の本体であることを発見し
て本発明を完成した。
本発明のマメ科ビスタリア属に属する植物の地
上部に発生する塊状瘤から分離された抗腫瘍性を
有する新規な多糖体の代表的な物理的および化学
的性質は下記の通りである。
性状：白色或いは微黄色の粉末
溶解性：水に溶けやすく、メタノール、エタ
ノール、アセトン、エーテル、シクロヘキサ
ン、石油エーテルおよび酢酸エチルにほとんど
溶けない。
安定性：本物質は熱水中で５時間安定であ
る。
元素分析値：Ｃ：39±３％、Ｈ：６±３％、
Ｎ：１±３％を示す。
単一性：ゲル過カラムを使用した高速液体
クロマトグラフイー〔高速液体クロマトグラフ
イー：Jasco tri rotar、使用ゲル：トーヨー
ソーダG5000PW、検出器：Shodex RISE−
31、溶媒：水〕により、本物質は第１図に示す
ように単一性を示す。
融点：融点測定器〔ヤナコ(株)製マイクロメル
テイングポイントアパラタス〕を使用した測定
により、本物質は明確な融点あるいは分解点を
示さない。
分子量：種々の分子量のデキストランおよび
ポリエチレンオキサイドを基準物質とし、ゲル
過カラムを使用した高速液体クロマトグラフ
イー〔高速液体クロマトグラフイー：Jasco
tri rotar、使用ゲル：トーヨーソーダ
G5000PW、検出器：Shodex RISE−31、溶
媒：水〕の結果より得た上記基準物質の溶出点
と、同じ高速液体クロマトグラフイーによる本
物質の分析パターンより、本物質の分子量範囲
は700000〜800000であると推定される（第２図
参照）。
呈色反応：本物質の水溶液を種々の呈色反応
について試験した結果を第１表に示す。
The present invention relates to a novel polysaccharide having antitumor properties, a method for producing the same, and further an antitumor agent containing the polysaccharide as an active ingredient. The lumpy lumps that occur on the above-ground parts of plants belonging to the genus Vistaria in the Fabaceae family are called Fujikobu, Fujinokobu, or Fujikobu, and are herbal medicines that have been used as folk medicine since ancient times for stomach health. As a result of screening tests for the antitumor effects of various herbal medicines, the present inventors found that lumpy nodules that occur on the aerial parts of plants belonging to the genus Vistaria in the Fabaceae family have excellent antitumor effects against experimental tumors in animals. It has been shown that this drug works. Focusing on this fact, we separated the active ingredient from the nodules that appear on the aerial parts of plants belonging to the genus Vistaria in the Fabaceae family, and succeeded in isolating and purifying a new polysaccharide.
The present invention was completed by discovering that the polysaccharide is the main body of antitumor action. Representative physical and chemical properties of the novel polysaccharide having antitumor properties isolated from the above-ground nodules of plants belonging to the genus Vistaria of the Fabaceae family of the present invention are as follows. Appearance: White or slightly yellow powder Solubility: Easily soluble in water, almost insoluble in methanol, ethanol, acetone, ether, cyclohexane, petroleum ether, and ethyl acetate. Stability: The material is stable in hot water for 5 hours. Elemental analysis value: C: 39 ± 3%, H: 6 ± 3%,
N: Indicates 1±3%. Uniformity: High performance liquid chromatography using a gel permeation column [High performance liquid chromatography: Jasco tri rotar, gel used: Toyo Soda G5000PW, detector: Shodex RISE−
31, solvent: water], this substance exhibits unity as shown in Figure 1. Melting point: This substance does not show a clear melting point or decomposition point when measured using a melting point measuring device [Micro Melting Point Apparatus manufactured by Yanaco Co., Ltd.]. Molecular weight: High performance liquid chromatography using a gel permeation column using dextran and polyethylene oxide of various molecular weights as reference materials [High performance liquid chromatography: Jasco
tri rotar, gel used: Toyo Soda
G5000PW, detector: Shodex RISE-31, solvent: water] From the elution point of the above reference substance obtained from the results and the analysis pattern of this substance by the same high performance liquid chromatography, the molecular weight range of this substance is 700,000 to 800,000. It is estimated that (see Figure 2). Color reaction: Table 1 shows the results of testing aqueous solutions of this substance for various color reactions.
【表】【table】
【表】
構成糖類：本物質を1Nトリフルオロ酢酸に
溶解後、100℃で２時間加水分解し、トリメチ
ルシリル化後、ガスクロマトグラフイーで分析
することにより、グルコースのみが検出され
る。
本発明の物質である抗腫瘍性多糖体を得るに
は、マメ科ビスタリア属に属する植物の地上部に
発生する瘤状塊を水性溶媒〔水、希薄な無機塩水
溶液（たとえば塩化ナトリウム、塩化カリウムな
どの水溶液）、弱酸性水溶液（たとえば0.05モル
までの酢酸、0.05モルまでのシユウ酸など）〕で
抽出し、この抽出液を濃縮した後、限外過また
は透析して低分子物質を除き、限外過内液また
は透析内液を濃縮後、フエノール−水系にて分配
する。更に遠心分離等の方法により水層を分取
し、親水性有機溶媒を加えて撹拌し、遠心分離し
て得られる沈殿を乾燥（例えば凍結乾燥）して粉
末（粗多糖体）を得る。上記製造過程において、
親水性有機溶媒としてはメタノール、エタノール
およびプロパノールを用いることが望ましいが、
ブタノール、アセトンあるいはこれらの親水性有
機溶媒の二種以上の混液を使用することもでき
る。
上記のようにして得た粉末（粗多糖体）は更に
精製される。精製には種々の方法が考えられる
が、その一つとしてゲル過クロマトグラフイー
を用いることができる。すなわち上記粉末を水に
溶解し、ゲル粒子としてトーヨーパールHW−65
を使用したゲル過クロマトグラフイーにかけ、
水性溶媒で展開してKd＝０〜0.5に相当する分画
を分取する。この分画を直接乾燥するか、減圧下
（30mmHg以下）で濃縮後、乾燥することにより、
白色〜微黄色の本発明の物質を得ることができ
る。
ゲル過クロマトグラフイーにおいてゲル粒子
としては、セフアデツクスＧ−75、Ｇ−100、Ｇ
−150、Ｇ−200、セフアロース2B、4B、6B、
CL−2B、CL−4B、CL−6B、バイオゲルＰ−
150、Ｐ−200、Ｐ−300およびトーヨーパール
HW−65、75などを使用することができ、展開に
用いる水性溶媒としては、水、希薄な無機塩水溶
液（たとえば塩化ナトリウム、塩化カリウムなど
の水溶液）、弱酸性水溶液（たとえば0.05モルま
での酢酸、0.05モルまでのシユウ酸など）を用い
て展開することができる。
ゲル過クロマトグラフイー以外の方法として
は、透析、限外過などの方法も使用できる。
次に本物質の抗腫瘍活性および安全性について
実験例をあげて説明する。
実験例 １
本物質の抗腫瘍活性
ICR系アルビノマウスにエーリツヒ腹水癌を移
植し、１週間後、腹水を採取し、別のマウスに一
匹当りエーリツヒ腹水癌細胞１×107個を腹腔中
に移植した。１群５匹とし、被験薬をそれぞれ癌
移植の翌日より１日１回５日間腹腔内投与した。
移植７日後に開腹して腹水を取り出し、これを
2000Gで５分間遠心分離して癌細胞を分離した。
この癌細胞の容積（Packed Cell Volume）を測
定し、対照群の癌細胞の容積に対する対照群と投
与群の癌細胞の容積の差のパーセンテージをもつ
て、癌細胞成長抑制率とした。
なお、被験薬は生理食塩水に溶解したものを使
用し、対照群には生理食塩水のみを投与した。本
発明である多糖体の癌細胞成長抑制率を第２表に
示す。[Table] Constituent sugars: Only glucose is detected by dissolving this substance in 1N trifluoroacetic acid, hydrolyzing it at 100°C for 2 hours, trimethylsilylating it, and analyzing it by gas chromatography. In order to obtain the antitumor polysaccharide which is the substance of the present invention, the nodules occurring on the aerial parts of plants belonging to the genus Vistaria of the Fabaceae family are prepared using an aqueous solvent [water, a dilute aqueous inorganic salt solution (e.g. sodium chloride, potassium chloride, etc.]). ), weakly acidic aqueous solution (for example, acetic acid up to 0.05 mol, oxalic acid up to 0.05 mol)], and after concentrating this extract, ultrafiltration or dialysis is performed to remove low-molecular substances. After concentrating the ultrafiltration fluid or dialysis fluid, it is distributed in a phenol-water system. Furthermore, the aqueous layer is separated by a method such as centrifugation, a hydrophilic organic solvent is added and stirred, and the precipitate obtained by centrifugation is dried (for example, freeze-dried) to obtain a powder (crude polysaccharide). In the above manufacturing process,
It is preferable to use methanol, ethanol and propanol as hydrophilic organic solvents, but
It is also possible to use butanol, acetone, or a mixture of two or more of these hydrophilic organic solvents. The powder (crude polysaccharide) obtained as described above is further purified. Various methods can be considered for purification, one of which is gel permeation chromatography. That is, the above powder was dissolved in water, and Toyo Pearl HW-65 was prepared as gel particles.
gel perchromatography using
Develop with an aqueous solvent and collect a fraction corresponding to Kd=0 to 0.5. By directly drying this fraction or by concentrating it under reduced pressure (30 mmHg or less) and then drying it,
A white to slightly yellow substance of the present invention can be obtained. Gel particles used in gel perchromatography include Sephadex G-75, G-100, and Gel particles.
-150, G-200, Cepharose 2B, 4B, 6B,
CL-2B, CL-4B, CL-6B, Biogel P-
150, P-200, P-300 and Toyo Pearl
HW-65, 75, etc. can be used, and the aqueous solvents used for development include water, dilute aqueous inorganic salt solutions (e.g., aqueous solutions of sodium chloride, potassium chloride, etc.), weakly acidic aqueous solutions (e.g., acetic acid up to 0.05 mol), , up to 0.05 mol of oxalic acid). Other than gel permeation chromatography, methods such as dialysis and ultrafiltration can also be used. Next, the antitumor activity and safety of this substance will be explained using experimental examples. Experimental Example 1 Antitumor activity of this substance Ehritzch ascites carcinoma was transplanted into ICR albino mice, and one week later, the ascites was collected, and 1×10 7 Ehritzch ascites carcinoma cells per mouse were intraperitoneally administered to another mouse. Ported. There were 5 animals in each group, and the test drug was intraperitoneally administered once a day for 5 days starting from the day after cancer transplantation.
Seven days after transplantation, the abdomen was opened and the ascites fluid was removed.
Cancer cells were separated by centrifugation at 2000G for 5 minutes.
The volume of the cancer cells (Packed Cell Volume) was measured, and the percentage of the difference between the volume of cancer cells in the control group and the administration group with respect to the volume of cancer cells in the control group was defined as the cancer cell growth inhibition rate. The test drug used was dissolved in physiological saline, and only physiological saline was administered to the control group. Table 2 shows the cancer cell growth inhibition rate of the polysaccharide of the present invention.
【表】
実験例 ２
本物質の急性毒性試験
ICR系アルビノマウスを１群10匹として用い、
これに本物質を経口投与、腹腔内投与、静脈注射
した場合のLD50は、いずれも1000mg／Kg以上で
あつた。このことより、本物質の安全性は、極め
て高いものと推定される。
本物質の抗腫瘍剤としての有効投与量は、患者
の年令、体重および疾患の程度により異なるが、
通常成人で１回50〜100mg、１日２〜３回までの
内服あるいは、１回10〜20mg、１日２〜３回まで
の静脈注射、筋肉内注射が適当と思われる。
また、本物質を抗腫瘍剤として用いるにあた
り、本物質に通常の製剤に用いられる賦形剤、補
助剤などを加えて製剤製法の常法に従つて、注射
剤、散剤、細粒剤、顆粒剤、錠剤、カプセル剤お
よびシロツプ剤などの製剤にして用いることもで
きる。
経口投与のために少くとも一種の賦形剤、例え
ばデンプン、乳糖、白糖、マンニツト、カルボキ
シメチルセルロース等を用いて錠剤、丸剤、カプ
セル剤、散剤、顆粒剤等に処方できる。
この種の製剤には、適宜前記賦形剤の他に、例
えばステアリン酸マグネシウム、ラウリル硫酸ナ
トリウム、タルク等の滑沢剤、デキストリン、結
晶セルロース、ポリビニルピロリドン、アラビア
ゴム、トウモロコシデンプン、ゼラチン等の結合
剤、バレイシヨデンプン、カルボキシメチルセル
ロール等の崩壊剤を使用することができる。
また懸濁液、エマルジヨン剤、シロツプ剤、エ
リキシル剤として投与することができ、これら剤
型には、矯味矯臭剤、着色在を含有してもよい。
非経口用製剤として、適当な基剤として混和し
てクリーム、軟膏剤、パツプ剤、注射剤または坐
剤とすることができる。
希釈剤として一般に注射用蒸留水、生理食塩
水、デキストロース水溶液、注射用植物油、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、適宜
等張化剤、溶解補助剤、安定剤、防腐剤、無痛化
剤等を加えてもよい。また、この種の剤型の場
合、滅菌された注射用媒体に溶解することが望ま
しい。
次に実施例を示して本発明を具体的に説明する
が、本発明はこれによりなんら制限されるもので
はない。
実施例 １
粗多糖体の分離
マメ科ビスタリア属に由来する植物であるノダ
フジ（Wistaria floribundaDC.）の地上部に発
生した塊状瘤を採集し、粉砕して４日間風乾し
た。このもの100ｇに水１を加え沸騰水浴上で
１時間熱水抽出し、熱時遠心分離して抽出液を得
た。残渣に水１を加え、再び沸騰水浴上で１時
間熱水抽出し、熱時遠心分離して抽出液を得、さ
らにもう１度この操作を行い、計３回の抽出液を
合せて減圧下で濃縮し、約300mlとした。この濃
縮液を限外過〔アルバツクサービス(株)製限外
過装置MC−6A、およびアミコン(株)製ダイヤフロ
ーメンブレン×M300限外過膜使用、分画分子
量30万〕し、限外過内液を減圧下で濃縮し、凍
結乾燥した。この乾燥物を２％の濃度になるよう
に精製水に溶解し、50％のフエノール−水系にて
分配し、一夜放置後、2000G、10分間遠心分離し
て水層を分取し、減圧下で濃縮して200mlとした
ものにアセトン800mlを加えて撹拌した後、遠心
分離した沈殿物を凍結乾燥して粉末（粗多糖体）
100mgを得た。
実施例 ２
多糖体のゲル過クロマトグラフイーによる精
製
実施例１で得られた粉末100mgを精製水10mlに
溶解し、トーヨーパールHW−65をつめたカラム
（3.0×50cm）にかけ、流速20ml／hr.にて0.01Mの
酢酸で展開した。流出液をフラクシヨンコレクタ
ーにて捕集し、各フラクシヨンとした。本発明の
物質は、Kd＝０〜0.5に含有されているので、そ
れに該当するフラクシヨン約450mlをまとめて、
減圧下で20mlまで濃縮して凍結乾燥し、目的とす
る抗腫瘍性多糖体である白色粉末27mgを得た。
このようにして得られた白色粉末は上記の理化
学的性質にすべてに適合するものであつた。
実施例 ３
マメ科ビスタリア属に由来する植物であるシラ
フジ（Wistaria venusta Rehd.et Wils）の地上
部に発生した塊状瘤を捕集し、粉砕して４日間風
乾した。このもの５Kgに水50を加えて抽出器で
１時間熱水抽出し、熱時遠心分離して抽出液を得
た。残渣に水50を加え、再び抽出器で１時間熱
水抽出し、熱時遠心分離して抽出液を得た。この
抽出液を前の抽出液と合せて減圧下で濃縮し、約
20とした。この濃縮液を限外過〔アルバツク
サービス(株)製限外過装置MC−6A、およびアミ
コン(株)製ダイヤフローメンブレン×M300限外
過膜使用、分画分子量30万〕し、限外過内液を
液膜流下式濃縮器で濃縮し、凍結乾燥した。この
乾燥物を２％の濃度になるように精製水に溶解
し、50％のフエノール−水系にて分配し、一夜放
置後、2000G、10分間遠心分離して水層を分取
し、液膜流下式濃縮器で濃縮して８としたもの
にメタノール32を加えて撹拌した後、遠心分離
した沈殿物を凍結乾燥して粉末（粗多糖体）６ｇ
を得た。この粉末６ｇを精製水250mlに溶解し、
セフアデツクス2Bをつめたカラム（10×100cm）
にかけて、流速800ml／hr.にて蒸溜水で展開し
た。Kd＝０〜0.5に相当する流出液１を取り、
減圧下で100mlまで濃縮して凍結乾燥し、目的と
する抗腫瘍性多糖体である白色粉末3.7ｇを得た。
このようにして得られた白色粉末は上記の理化
学的性質にすべて適合するものであつた。
実施例 ４
実施例２で得られた白色粉末30ｇを微結晶セル
ロース155ｇおよびステアリン酸マグネシウム５
ｇと混合し、この混合物を単発式打錠機にて打錠
して直径７mm、重量190mgの錠剤を製造した。
本錠剤１錠中には実施例２において得られた白
色粉末を30mg含有する。本錠剤は症状にあわせて
１回２〜３錠を１日３回服用する。
実施例 ５
実施例２で得られた白色粉末10ｇをトウモロコ
シデンプン490ｇと混合し水を加えて練合し、１
mm×１mmの網目を有するスクリーンにて造粒して
乾燥し顆粒剤とした。
本顆粒剤１ｇ中には実施例２において得られた
白色粉末を20mg含有する。本顆粒剤は症状にあわ
せて１回３〜５ｇを１日３回服用する。
実施例 ６
実施例３で得られた白色粉末20ｇを乳糖70ｇお
よびステアリン酸マグネシウム10ｇと混合し、
500mgづつ硬カプセルに充填した。
本カプセル剤１カプセル中には実施例３で得ら
れた白色粉末100mg含有する。本カプセル剤は症
状にあわせて１回１カプセルを１日２〜３回服用
する。
実施例 ７
実施例３で得られた白色粉末10ｇを水80mlに溶
解し、オレンジエツセンス２mlおよび単シロツプ
を加えて全量1000mlのシロツプ剤とした。
本シロツプ剤１ml中には実施例３で得られた白
色粉末を10mg含有する。本シロツプ剤は症状にあ
わせて１回５〜10mlを１日３回服用する。
実施例 ８
実施例３で得られた白色粉末５ｇを注射製造の
常法に従つて、注射用蒸留水１に溶解し、塩化
ナトリウムを加えることにより等張化し、10mlづ
つバイアルに分注して注射剤とした。
本注射剤１ml中には実施例３で得られた白色粉
末を５mg含有する。本注射剤は症状にあわせて１
回２〜４mlを１日３回静脈注射あるいは筋肉内注
射する。[Table] Experimental Example 2 Acute toxicity test of this substance ICR albino mice were used in a group of 10 mice.
In addition, when this substance was administered orally, intraperitoneally, and intravenously, the LD 50 was all 1000 mg/Kg or more. From this, it is estimated that the safety of this substance is extremely high. The effective dose of this substance as an antitumor agent varies depending on the age, weight, and severity of the disease of the patient.
Oral administration of 50 to 100 mg at a time, up to 2 to 3 times a day, or intravenous or intramuscular injection at a time of 10 to 20 mg, up to 2 to 3 times a day, is usually appropriate for adults. In addition, when using this substance as an antitumor agent, it is possible to add excipients, adjuvants, etc. used in ordinary formulations to this substance, and prepare injections, powders, fine granules, and granules according to the conventional method for manufacturing formulations. It can also be used in the form of preparations such as tablets, capsules and syrups. For oral administration, they can be formulated into tablets, pills, capsules, powders, granules, etc. using at least one excipient such as starch, lactose, sucrose, mannitrate, carboxymethyl cellulose, etc. In addition to the above-mentioned excipients, this type of preparation may contain, for example, lubricants such as magnesium stearate, sodium lauryl sulfate, and talc, binders such as dextrin, crystalline cellulose, polyvinylpyrrolidone, gum arabic, corn starch, and gelatin. Disintegrants such as silica, potato starch, carboxymethyl cellulose, etc. can be used. It can also be administered as a suspension, emulsion, syrup, or elixir, and these dosage forms may contain flavoring agents and coloring agents. As a parenteral preparation, it can be mixed with a suitable base to form a cream, ointment, poultice, injection, or suppository. As a diluent, distilled water for injection, physiological saline, aqueous dextrose solution, vegetable oil for injection, propylene glycol, polyethylene glycol, etc. can generally be used. Furthermore, if necessary, an isotonizing agent, a solubilizing agent, a stabilizer, a preservative, a soothing agent, etc. may be added as appropriate. Moreover, in the case of this type of dosage form, it is desirable to dissolve it in a sterile injection medium. EXAMPLES Next, the present invention will be specifically explained with reference to Examples, but the present invention is not limited thereto in any way. Example 1 Separation of Crude Polysaccharide A lump that had developed on the aerial part of Wistaria floribunda DC., a plant derived from the genus Vistaria of the Fabaceae family, was collected, crushed, and air-dried for 4 days. To 100 g of this product, 1 part of water was added, hot water extraction was carried out for 1 hour on a boiling water bath, and the extract was centrifuged while hot to obtain an extract. Add 1 part of water to the residue, perform hot water extraction again on a boiling water bath for 1 hour, centrifuge while hot to obtain an extract, repeat this operation once more, and combine the three extractions and extract under reduced pressure. It was concentrated to about 300 ml. This concentrated solution was subjected to ultrafiltration (using an ultrafiltration device MC-6A manufactured by Albac Service Co., Ltd. and a Diaflow membrane x M300 ultrafiltration membrane manufactured by Amicon Co., Ltd., molecular weight cut off 300,000). The internal solution was concentrated under reduced pressure and lyophilized. This dried product was dissolved in purified water to a concentration of 2%, distributed in a 50% phenol-water system, left overnight, centrifuged at 2000G for 10 minutes to separate the aqueous layer, and under reduced pressure. After adding 800 ml of acetone and stirring, the precipitate was centrifuged and the precipitate was freeze-dried to form a powder (crude polysaccharide).
Got 100mg. Example 2 Purification of polysaccharide by gel permeation chromatography 100 mg of the powder obtained in Example 1 was dissolved in 10 ml of purified water and applied to a column (3.0 x 50 cm) packed with Toyo Pearl HW-65 at a flow rate of 20 ml/hr. Developed with 0.01M acetic acid. The effluent was collected with a fraction collector to obtain each fraction. Since the substance of the present invention is contained in a Kd of 0 to 0.5, approximately 450 ml of the corresponding fraction is collected,
The mixture was concentrated to 20 ml under reduced pressure and lyophilized to obtain 27 mg of white powder, which is the desired antitumor polysaccharide. The white powder thus obtained met all of the above physical and chemical properties. Example 3 Nodules that had developed on the aerial parts of Wistaria venusta Rehd.et Wils, a plant derived from the genus Vistaria of the Fabaceae family, were collected, crushed, and air-dried for 4 days. 5kg of this product was added with 50ml of water, extracted with hot water for 1 hour using an extractor, and centrifuged while hot to obtain an extract. 50 g of water was added to the residue, and hot water extraction was performed again using an extractor for 1 hour, followed by centrifugation while hot to obtain an extract. This extract was combined with the previous extract and concentrated under reduced pressure to approx.
It was set at 20. This concentrated solution was subjected to ultrafiltration (using an ultrafiltration device MC-6A manufactured by Albac Service Co., Ltd. and a Diaflow membrane x M300 ultrafiltration membrane manufactured by Amicon Co., Ltd., molecular weight cut off 300,000). The internal solution was concentrated using a falling film concentrator and freeze-dried. This dried product was dissolved in purified water to a concentration of 2%, distributed in a 50% phenol-water system, left overnight, centrifuged at 2000G for 10 minutes to separate the aqueous layer, and a liquid film was formed. After concentrating with a down-flow concentrator to a concentration of 8, methanol 32 was added and stirred, and the centrifuged precipitate was freeze-dried to obtain 6 g of powder (crude polysaccharide).
I got it. Dissolve 6g of this powder in 250ml of purified water,
Column packed with Sefadex 2B (10 x 100cm)
The mixture was developed with distilled water at a flow rate of 800 ml/hr. Take the effluent 1 corresponding to Kd=0~0.5,
The mixture was concentrated to 100 ml under reduced pressure and lyophilized to obtain 3.7 g of white powder, which is the desired antitumor polysaccharide. The white powder thus obtained met all of the above physical and chemical properties. Example 4 30 g of the white powder obtained in Example 2 was mixed with 155 g of microcrystalline cellulose and 5 g of magnesium stearate.
This mixture was compressed using a single-shot tablet machine to produce tablets with a diameter of 7 mm and a weight of 190 mg. One tablet contains 30 mg of the white powder obtained in Example 2. This tablet is taken 2 to 3 tablets at a time, three times a day, depending on the symptoms. Example 5 10g of the white powder obtained in Example 2 was mixed with 490g of corn starch, water was added and kneaded, and 1
The mixture was granulated and dried using a screen having a mesh size of mm x 1 mm to obtain granules. 1 g of this granule contains 20 mg of the white powder obtained in Example 2. This granule is taken at a dose of 3 to 5 g three times a day, depending on the symptoms. Example 6 20 g of the white powder obtained in Example 3 was mixed with 70 g of lactose and 10 g of magnesium stearate,
500 mg each was filled into hard capsules. One capsule of the present invention contains 100 mg of the white powder obtained in Example 3. This capsule is taken at a time, 1 capsule 2 to 3 times a day, depending on the symptoms. Example 7 10 g of the white powder obtained in Example 3 was dissolved in 80 ml of water, and 2 ml of orange essence and simple syrup were added to make a syrup with a total volume of 1000 ml. 1 ml of this syrup contains 10 mg of the white powder obtained in Example 3. This syrup is taken at a dose of 5 to 10 ml three times a day, depending on the symptoms. Example 8 5 g of the white powder obtained in Example 3 was dissolved in 1 part of distilled water for injection according to the usual method for injection manufacturing, made isotonic by adding sodium chloride, and dispensed into vials in 10 ml portions. It was made into an injection. 1 ml of this injection contains 5 mg of the white powder obtained in Example 3. This injection is administered in 1 dose according to the symptoms.
Inject 2 to 4 ml intravenously or intramuscularly three times a day.
第１図はゲル過カラムを使用した高速液体ク
ロマトグラフイーによる本発明多糖体の分析パタ
ーンを示す図であり、第２図は同じ高速液体クロ
マトグラフイーによる種々の分子量の基準物質の
溶出点と本発明多糖体の分析パターンを示す図で
ある。
Figure 1 shows the analysis pattern of the polysaccharide of the present invention by high performance liquid chromatography using a gel permeation column, and Figure 2 shows the elution points and elution points of reference substances of various molecular weights by the same high performance liquid chromatography. FIG. 3 is a diagram showing an analysis pattern of the polysaccharide of the present invention.
Claims (1)
発生する塊状瘤より得られ、構成糖が主としてグ
ルコースであり、水に溶けやすくメタノール、エ
タノール、アセトン、エーテル、シクロヘキサ
ン、石油エーテルおよび酢酸エチルにほとんど溶
けず、元素分析においてＣ：39±３％、Ｈ：６±
３％、Ｎ：１±３％であり、分子量範囲が700000
〜800000である多糖体。 ２ マメ科ビスタリア属に属する植物の地上部に
発生する塊状瘤の水性溶媒抽出液を限外過また
は透析して低分子物質を除き、限外過内液また
は透析内液を濃縮後、フエノール−水の系にて分
配し、水層を分取し親水性有機溶媒を加えて得ら
れる沈殿を精製することを特徴とする、構成糖が
主としてグルコースであり、水に溶けやすくメタ
ノール、エタノール、アセトン、エーテル、シク
ロヘキサン、石油エーテルおよび酢酸メチルにほ
とんど溶けず、元素分析においてＣ：39±３％、
Ｈ：６±３％、Ｎ：１±３％であり、分子量範囲
が700000〜800000である多糖体の製造方法。 ３ マメ科ビスタリア属に属する植物の地上部に
発生する塊状瘤より得られ、構成糖が主としてグ
ルコースであり、水に溶けやすくメタノール、エ
タノール、アセトン、エーテル、シクロヘキサ
ン、石油エーテルおよび酢酸エチルにほとんど溶
けず、元素分析において、Ｃ：39±３％、Ｈ：６
±３％、Ｎ：１±３％であり、分子量範囲が
700000〜800000である多糖体を有効成分とする抗
腫瘍剤。[Scope of Claims] 1. Obtained from the agglomerates that occur on the aerial parts of plants belonging to the genus Vistaria of the Fabaceae family, whose constituent sugars are mainly glucose, and which are easily soluble in water such as methanol, ethanol, acetone, ether, cyclohexane, and petroleum ether. It is hardly soluble in ethyl acetate, and elemental analysis reveals that C: 39±3%, H: 6±
3%, N: 1±3%, molecular weight range is 700000
~800000 polysaccharides. 2. Ultrafiltration or dialysis of the aqueous solvent extract of the nodules that occur on the aerial parts of plants belonging to the genus Vistaria of the Fabaceae family to remove low-molecular substances, and concentrating the ultrafiltration or dialysis solution, followed by phenol-filtration. It is characterized by partitioning in an aqueous system, separating the aqueous layer, and purifying the resulting precipitate by adding a hydrophilic organic solvent.The constituent sugars are mainly glucose, and it is easily soluble in water, including methanol, ethanol, and acetone. , almost insoluble in ether, cyclohexane, petroleum ether and methyl acetate, C: 39 ± 3% in elemental analysis,
A method for producing a polysaccharide having H: 6±3%, N: 1±3% and a molecular weight range of 700,000 to 800,000. 3 Obtained from the nodules that occur on the aerial parts of plants belonging to the genus Vistaria in the Fabaceae family, and the constituent sugar is mainly glucose, which is easily soluble in water and almost soluble in methanol, ethanol, acetone, ether, cyclohexane, petroleum ether, and ethyl acetate. In elemental analysis, C: 39 ± 3%, H: 6
±3%, N: 1±3%, and the molecular weight range is
An antitumor agent whose active ingredient is a polysaccharide with a molecular weight of 700,000 to 800,000.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58190824A JPS6084301A (en) | 1983-10-14 | 1983-10-14 | Polysaccharide, its production, and antineoplastic agent containing said polysaccharide as active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58190824A JPS6084301A (en) | 1983-10-14 | 1983-10-14 | Polysaccharide, its production, and antineoplastic agent containing said polysaccharide as active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6084301A JPS6084301A (en) | 1985-05-13 |
| JPH052684B2 true JPH052684B2 (en) | 1993-01-13 |
Family
ID=16264367
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58190824A Granted JPS6084301A (en) | 1983-10-14 | 1983-10-14 | Polysaccharide, its production, and antineoplastic agent containing said polysaccharide as active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6084301A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110283256A (en) * | 2019-06-28 | 2019-09-27 | 湖北民族大学 | A method of extracting Machilus nanmu polysaccharide from Machilus nanmu leaf |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITPD20040241A1 (en) * | 2004-10-04 | 2005-01-04 | Alpina Raggi Spa | RADIUS TOGETHER AND NIPPLO FOR WHEEL WITH SPOKES AND WHEEL WITH RAYS INCLUDING A PLURALITY OF THOSE SETS |
-
1983
- 1983-10-14 JP JP58190824A patent/JPS6084301A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110283256A (en) * | 2019-06-28 | 2019-09-27 | 湖北民族大学 | A method of extracting Machilus nanmu polysaccharide from Machilus nanmu leaf |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6084301A (en) | 1985-05-13 |
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