JPH0278630A - Antitumor agent - Google Patents
Antitumor agentInfo
- Publication number
- JPH0278630A JPH0278630A JP63228848A JP22884888A JPH0278630A JP H0278630 A JPH0278630 A JP H0278630A JP 63228848 A JP63228848 A JP 63228848A JP 22884888 A JP22884888 A JP 22884888A JP H0278630 A JPH0278630 A JP H0278630A
- Authority
- JP
- Japan
- Prior art keywords
- extracted
- antitumor
- residue
- protein polysaccharide
- antitumor agent
- 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
Links
- 239000002246 antineoplastic agent Substances 0.000 title claims abstract description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 21
- 239000000126 substance Substances 0.000 claims abstract description 11
- 150000004676 glycans Chemical class 0.000 claims abstract description 10
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 10
- 239000005017 polysaccharide Substances 0.000 claims abstract description 10
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 10
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000000862 absorption spectrum Methods 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 238000000921 elemental analysis Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- OQUKIQWCVTZJAF-UHFFFAOYSA-N phenol;sulfuric acid Chemical compound OS(O)(=O)=O.OC1=CC=CC=C1 OQUKIQWCVTZJAF-UHFFFAOYSA-N 0.000 claims description 2
- 101100335897 Caenorhabditis elegans gly-9 gene Proteins 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 9
- 238000000605 extraction Methods 0.000 abstract description 9
- 235000001674 Agaricus brunnescens Nutrition 0.000 abstract description 5
- 235000013399 edible fruits Nutrition 0.000 abstract description 5
- 241000222518 Agaricus Species 0.000 abstract description 4
- 239000002244 precipitate Substances 0.000 abstract description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 abstract description 3
- VBIXEXWLHSRNKB-UHFFFAOYSA-N ammonium oxalate Chemical compound [NH4+].[NH4+].[O-]C(=O)C([O-])=O VBIXEXWLHSRNKB-UHFFFAOYSA-N 0.000 abstract description 3
- 241001327634 Agaricus blazei Species 0.000 abstract 3
- 239000004480 active ingredient Substances 0.000 abstract 2
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 238000002523 gelfiltration Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000003809 water extraction Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000006268 Sarcoma 180 Diseases 0.000 description 1
- HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- -1 alditol acetate Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- RJGDLRCDCYRQOQ-UHFFFAOYSA-N anthrone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 RJGDLRCDCYRQOQ-UHFFFAOYSA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、ハラタケ属（Ａｇａｒｌｃｕｓ）のキノコで
あるカワリハラタケ（通称ヒメマツタケ）（Ａｇａｒｉ
ｃｕｓ−ｂｌａｚｅｉ）の子実体中に存在１−１抗腫瘍
活性を持つ新規な蛋白多糖体に関する。[Detailed Description of the Invention] <Industrial Application Field> The present invention is directed to the use of Agaricus mushroom (Commonly known as Himematsutake), which is a mushroom of the genus Agaricus.
The present invention relates to a novel protein polysaccharide having 1-1 antitumor activity present in the fruiting bodies of A. cus-blazei).
〈従来の技術〉
カワリハラタケ自体は民間でこれまで糖尿病や高血圧の
治療および抗腫瘍剤の一種として利用されてきた。 ま
た、カワリハラタケｒ実体より抗腫瘍作用を有する水溶
性の蛋白多糖体の製法については、特開昭５５−７４７
９７号に記載されている。<Prior Art> Kawariharatake itself has been used in the private sector to treat diabetes and hypertension, and as a type of antitumor agent. In addition, regarding the production method of water-soluble protein polysaccharide having antitumor activity from Kawariharatake r substance, Japanese Patent Application Laid-Open No. 55-747
It is described in No. 97.
〈発明が解決しようとしている問題点〉カワリハラタケ
子実体の熱水抽出物中には、抗腫瘍作用を持つ多糖体や
、核酸成分が分離されている。しかしながら、熱水抽出
残渣から抗腫瘍性物質の分離は行われていない。<Problems to be solved by the invention> Polysaccharides and nucleic acid components that have antitumor effects are isolated in the hot water extract of the fruiting bodies of Kawariharatake mushrooms. However, antitumor substances have not been separated from the hot water extraction residue.
本発明はカワリハラタケ熱水抽出残渣から抗腫瘍性物質
を分離し、抗腫瘍剤として応用しようとするものである
。The present invention aims to separate an antitumor substance from the hot water extraction residue of Kawariharatake mushroom and apply it as an antitumor agent.
〈問題点を解決するための手段〉
本発明者等はカワリハラタケ子実体の熱水抽出残渣をア
ルカリ抽出し、抽出物の抗腫瘍性を検討した結果、著し
い抗腫瘍性を示すことを見い出した。さらにその本体の
構造は、従来の抗腫瘍多糖の構造とは異なるβ（１−６
）−Ｄ−グルカンと蛋白質の複合体と判明し、本発明の
完成に至った。<Means for Solving the Problems> The present inventors subjected the hot water extraction residue of Kawariharatake fruiting bodies to alkali extraction, examined the antitumor properties of the extract, and found that the extract exhibited significant antitumor properties. Furthermore, the structure of its main body is different from that of conventional antitumor polysaccharides.
)-D-glucan and a protein, leading to the completion of the present invention.
カワリハラタケ子実体からこの発明の抗腫瘍性物質を抽
出、分離するには例えば次のような方法で得ることがで
きる。まず生の子実体、乾燥した子実体を使用し、生の
子実体の場合は千切りにし、乾燥品の場合には粉砕する
。千切りあるいは粉砕した子実体は低級脂肪族アルコー
ルあるいは２０％以下の水を含有する低級脂肪族アルコ
ールによって抽出前処理することにより低分子成分を除
去する。次に、残渣を熱水で抽出し、水溶性成分を除去
する。この・抽出残渣を風乾し、シュウ酸アンモニウム
で抽出を行う。さらに、その抽出残渣に５％水酸化ナト
リウム水溶液を加え３０℃で抽出を行う。この抽出液を
酢酸で中和し、ｐＨ５〜６に調整し、生じた沈澱を除去
する。次にゲルが過によって、蛋白質・多糖体画分を分
離する。そしてこれを透析し、その他の公知の精製手段
に上り脱塩精製し、精製液を濃縮した後、常法によって
凍結乾燥すると灰白色粉末体を得ることができる。The antitumor substance of the present invention can be extracted and separated from the fruiting bodies of Agaricus agaricus by, for example, the following method. First, use raw fruiting bodies and dried fruiting bodies, and if the fruiting bodies are raw, they are cut into strips, and if they are dried, they are crushed. The shredded or crushed fruit bodies are pre-extracted with a lower aliphatic alcohol or a lower aliphatic alcohol containing 20% or less water to remove low molecular components. Next, the residue is extracted with hot water to remove water-soluble components. This extraction residue is air-dried and extracted with ammonium oxalate. Furthermore, a 5% aqueous sodium hydroxide solution is added to the extraction residue and extraction is performed at 30°C. This extract is neutralized with acetic acid, the pH is adjusted to 5 to 6, and the resulting precipitate is removed. Next, the gel is filtered to separate protein and polysaccharide fractions. Then, this is dialyzed, desalted and purified by other known purification means, the purified liquid is concentrated, and then freeze-dried by a conventional method to obtain an off-white powder.
このようにして得られた物質は、以下に説明する理化学
的性質を有し、後述する動物試験の結果から抗腫瘍剤と
して有効な物質と認められる。The substance thus obtained has the physicochemical properties described below, and is recognized as an effective substance as an antitumor agent based on the results of animal tests described below.
（＋）理化学的性質
（イ）元素分析の結果Ｃ４１，８７％、Ｈ７，１５％、
Ｎ６．８８％であり、フェノール・硫酸法による糖含１
（グルコース換算）４３４％、Ｌｏｗｒｙ法による蛋白
質（牛アルブミン換算）５０．２％を含有する蛋白多糖
体である。構成糖はアルジトール・アセテートのガスク
ロマトグラフィーで大部分はグルコースから成り微量の
キシロース、ガラクトース、マルトースを含有する。(+) Physical and chemical properties (a) Elemental analysis results C41.87%, H7.15%,
N6.88%, sugar content 1 by phenol/sulfuric acid method
It is a protein polysaccharide containing 434% (in terms of glucose) and 50.2% protein (in terms of bovine albumin) determined by the Lowry method. The constituent sugars are mostly glucose, as determined by alditol acetate gas chromatography, and contain trace amounts of xylose, galactose, and maltose.
箱守法によるメチル化分析及びＩＨ，′３ＣＮＭＲ分析
によりグルコースのβ１→６結合を認める。Methylation analysis using the Hakomori method and IH,'3CNMR analysis revealed a β1→6 linkage of glucose.
（ロ）ゲルが過によって求めた分子量は約１〜５万であ
る。(b) The gel has a molecular weight of approximately 10,000 to 50,000 determined by filtration.
（ハ）比旋光度〔Ｕ〕ｏ’＝ ２３，０°（ｃ ＝１
．０ 、５％Ｎａ０Ｈ）で左旋性を示す。(c) Specific rotation [U] o' = 23,0° (c = 1
．． 0, 5% NaOH) shows levorotation.
（ニ）赤外線吸収スペクトルをＫＢｒ錠剤法で測定し、
これを第１図に示す。(d) Measure the infrared absorption spectrum by the KBr tablet method,
This is shown in FIG.
（ホ）核磁気共鳴スペクトル（”Ｃ−Ｎ Ｍ Ｒ）を、
０．３Ｍ Ｎａ０Ｄに溶解し、測定し、これを第２図に
示す。(e) Nuclear magnetic resonance spectrum (C-NMR),
It was dissolved in 0.3M NaOD and measured, which is shown in FIG.
（へ）１〜１０％水酸化ナトリウム等のアルカリに可溶
であり、水、酸およびＤＭＳＯ（ジメチルスルフオキシ
ド）にやや溶解し、有機溶媒たとえばエタノール、アセ
トン、エーテル、クロロホルム等には不溶である。(f) Soluble in alkalis such as 1-10% sodium hydroxide, slightly soluble in water, acids and DMSO (dimethyl sulfoxide), and insoluble in organic solvents such as ethanol, acetone, ether, chloroform, etc. be.
（ト）アンスロン硫酸試薬、ニンヒドリン反応試薬に対
して陽性である。(g) Positive for Anthrone sulfate reagent and ninhydrin reaction reagent.
（ヂ）凍結乾燥によって得られた粉末は灰白色を呈する
。(d) The powder obtained by freeze-drying has a grayish-white color.
（す）アミノ酸組成（モル％） ６Ｍ塩酸と１１０’
Ｃ，２０時間加水分解したものを、日立８３５型アミノ
酸分析計によって測定した結果Ａｓｐ １０．７゜Ｔｈ
ｒ ５．２． Ｓｅｒ ５．３． Ｇｌｕ １１．１．
Ｇｌｙ ９Ｊ、 ＡＩａｌｌ、９． Ｍａｌ ４．９
． Ｍｅｔ １．１． Ｉｌｅ ３Ｊ、 Ｌｅｕ １０
゜８、 Ｔｙｒ ２．４． Ｐｈｅ ４．５． Ｌｙｓ
５Ｊ、 Ｈｉｓ ２．１゜Ａｒｇ５．２． Ｐｒｏ
６．９を示す。(S) Amino acid composition (mol%) 6M hydrochloric acid and 110'
C. Asp 10.7゜Th when hydrolyzed for 20 hours and measured using a Hitachi 835 amino acid analyzer.
r5.2. Ser 5.3. Glu 11.1.
Gly 9J, AIall, 9. Mal 4.9
．． Met 1.1. Ile 3J, Leu 10
゜8, Tyr 2.4. Phe 4.5. Lys
5J, His 2.1°Arg5.2. Pro
6.9 is shown.
〈作用〉
次に本発明の抗腫瘍剤の急性毒性および薬理作用につい
て述べる。<Action> Next, the acute toxicity and pharmacological action of the antitumor agent of the present invention will be described.
（１）急性毒性
ＩＣＲマウス（雌、５週令）の腹腔内または経口１回投
与による急性毒性試験（１週間観察）において、本発明
抗腫瘍剤は５００ｍｇ／ｋｇで死亡率はともに０７７で
あるマウスにおける重大な体重変化は見られなかった。(1) Acute toxicity In an acute toxicity test (observation for 1 week) by intraperitoneal or oral administration once to ICR mice (female, 5 weeks old), the antitumor agent of the present invention had a mortality rate of 0.77 at 500 mg/kg. No significant body weight changes were observed in the mice.
（２）薬理作用
ａ）試験例Ｉ （腹腔内投与法）
サルコーマ１８０固形癌に対する効果
■ＣＲＣウマウス腋窩下で継代されているサルコーマ１
８０の固形癌細胞（直径３ｍｍ）をトロツカールでＩＣ
Ｒマウス（雌４迎合）の腋窩部皮下に移植し、移植２４
時間後より、本発明の抗腫瘍剤を腹腔内に投与した。投
与回数は１日１回ＩＯ日間とし、移植３週間後に腫瘍直
径を測定し、それを対照群と比較してｌＩｔ瘍抑制率を
算出した。また６週間後には、腫瘍完全消失率と死亡率
を調べた。その結果を第１表に示す。(2) Pharmacological effects a) Test example I (intraperitoneal administration method) Effect on Sarcoma 180 solid tumor■ Sarcoma 1 passaged in the subaxillary fossa of CRC horse mice
IC of 80 solid tumor cells (3 mm in diameter) with Trotzcar
Transplanted subcutaneously into the axillary region of R mice (female 4 p.i.), transplantation 24
After some time, the antitumor agent of the present invention was intraperitoneally administered. The administration frequency was once a day for 10 days, and the tumor diameter was measured 3 weeks after transplantation and compared with the control group to calculate the lIt tumor suppression rate. After 6 weeks, the tumor complete disappearance rate and mortality rate were examined. The results are shown in Table 1.
〈実施例〉
乾燥したカワリハラタケ子実体１００ｇに２１２の８５
％エタノールを加え、８０℃で加熱還流抽出を３回行っ
た。抽出残渣に２夕の１％ンユウ酸アンモニウムを加え
１００℃で抽出を行い冷却後、が別した。<Example> 85 of 212 in 100 g of dried Kawariharatake fruiting body
% ethanol was added, and extraction was performed three times under heating at 80°C under reflux. 1% ammonium oxalate was added to the extraction residue for two nights and extraction was carried out at 100° C. After cooling, the mixture was separated.
その抽出残渣をさらに５％水酸化ナトリウムＩＬ３０℃
で抽出した。得られた抽出液を酢酸で中和し、生じた不
溶物を除去し、最終濃度が８０％になるようにエタノー
ルを加えた。この時相じた沈澱物を遠心分離によって回
収した。沈澱物は０．３Ｍ水酸化ナトリウムに溶解し、
トヨパールＨＷ−５５Ｓカラム（４Ｘ ５０ｃｍ）を用
いてゲルが過を行った。フェノール硫酸法による４８５
ｎｍに吸収のあるフラクションを集め、透析、凍結乾燥
することにより抗腫瘍物質を７．５ｇ得た。The extraction residue was further treated with 5% sodium hydroxide IL at 30°C.
Extracted with. The obtained extract was neutralized with acetic acid, the resulting insoluble materials were removed, and ethanol was added to give a final concentration of 80%. At this time, the resulting precipitate was collected by centrifugation. The precipitate was dissolved in 0.3M sodium hydroxide,
The gel was filtered using a Toyopearl HW-55S column (4×50 cm). 485 by phenol sulfuric acid method
Fractions with absorption at nm were collected, dialyzed, and freeze-dried to obtain 7.5 g of an antitumor substance.
第１図は赤外線吸収スペクトルを示す。第２図は核磁気
共鳴スペクトルを示す。
特許出願人 代表者株式会社ニチレイFIG. 1 shows the infrared absorption spectrum. Figure 2 shows the nuclear magnetic resonance spectrum. Patent applicant Representative Nichirei Co., Ltd.
Claims (1)
体由来の蛋白多糖体からなる抗腫瘍剤 （イ）元素分析：Ｃ４１．８７％ Ｈ７．１５％Ｎ６．
８８％ 糖含量５０．２％ タンパク質含量４３．３％ （ロ）分子量：１〜５万 （ハ）比旋光度：〔α〕＾２＾５＿Ｄ＝−２３．０゜（
ｃ＝１．０、５％ＮａＯＨ） （ニ）赤外線吸収スペクトル：第１図に示す。 （ホ）核磁気共鳴スペクトル：第２図に示す。 （ヘ）溶解性：アルカリに可溶、水、ＤＭＳＯ（ジメチ
ルスルフォキシド）にやや溶解、有機溶媒に不溶 （ト）呈色反応：フェノール硫酸およびニンヒドリン反
応に陽性 （チ）色：灰白色 （リ）アミノ酸組成（モル％）：Ａｓｐ１０．７、Ｔｈ
ｒ５．２、Ｓｅｒ５．３、Ｇｌｕ１１．１、Ｇｌｙ９．
３、Ａｌａ１１．９、Ｖａｌ４．９、Ｍｅｔ１．１、Ｉ
ｌｅ３．３、Ｌｅｕ１０．８、Ｔｙｒ２．４、Ｐｈｅ４
．５、Ｌｙｓ５．３、Ｈｉｓ２．１、Ａｒｇ５．２、Ｐ
ｒｏ６．９、合計１００％。(1) Anti-tumor agent consisting of protein polysaccharide derived from Kawariharatake fruiting body having the following physical and chemical properties (a) Elemental analysis: C41.87% H7.15% N6.
88% Sugar content 50.2% Protein content 43.3% (b) Molecular weight: 10,000 to 50,000 (c) Specific rotation: [α] ^2^5_D = -23.0° (
c=1.0, 5% NaOH) (d) Infrared absorption spectrum: shown in FIG. (e) Nuclear magnetic resonance spectrum: Shown in FIG. (F) Solubility: Soluble in alkali, slightly soluble in water, DMSO (dimethyl sulfoxide), insoluble in organic solvents (G) Color reaction: Positive for phenol sulfuric acid and ninhydrin reactions (H) Color: Gray-white (liquid) ) Amino acid composition (mol%): Asp10.7, Th
r5.2, Ser5.3, Glu11.1, Gly9.
3, Ala11.9, Val4.9, Met1.1, I
le3.3, Leu10.8, Tyr2.4, Phe4
．． 5, Lys5.3, His2.1, Arg5.2, P
ro6.9, total 100%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63228848A JPH0278630A (en) | 1988-09-14 | 1988-09-14 | Antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63228848A JPH0278630A (en) | 1988-09-14 | 1988-09-14 | Antitumor agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0278630A true JPH0278630A (en) | 1990-03-19 |
Family
ID=16882821
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63228848A Pending JPH0278630A (en) | 1988-09-14 | 1988-09-14 | Antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0278630A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06239761A (en) * | 1993-02-12 | 1994-08-30 | Hitoshi Ito | Agent for internal use, food and drink having appetite stimulating action |
| FR2721932A1 (en) * | 1994-06-30 | 1996-01-05 | Palmer Research | New glyco-protein from edible mushrooms |
| WO1998027992A1 (en) * | 1996-12-20 | 1998-07-02 | Sumitomo Forestry Co., Ltd. | Antitumor active substances |
| EP0939082A1 (en) * | 1998-01-16 | 1999-09-01 | Agaricus Laboratories Co., Ltd. | Protein polysaccharide 0041 |
| JP2001240603A (en) * | 2000-02-29 | 2001-09-04 | Toei Shinyaku Kk | beta-1,3-BRANCHED beta-1,6-GLUCAN AND ALKALI EXTRACTED ESSENCE OF AGARICUS MUSHROOM |
| US6627201B2 (en) | 2001-04-03 | 2003-09-30 | Kabushiki Kaisha Sun Chlorella | Composition for drinking/eating and beverage/food |
| JP2007291001A (en) * | 2006-04-24 | 2007-11-08 | Bizen Chemical Co Ltd | New anticancer agent |
| JP2014001188A (en) * | 2012-06-20 | 2014-01-09 | Hiroko Ito | Neovascularization inhibitor, and food and drink composition for inhibiting neovascularization |
| JP2018083807A (en) * | 2016-11-11 | 2018-05-31 | 株式会社岩出菌学研究所 | Anticancer agent tolerance inhibitor having immune checkpoint inhibitory function, and method for producing the same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5574797A (en) * | 1978-12-04 | 1980-06-05 | Mitsubishi Yuka Yakuhin Kk | Preparation of protein polysaccharide having anti-tumor activity |
| JPS55108293A (en) * | 1979-02-15 | 1980-08-20 | Mitsubishi Yuka Yakuhin Kk | Production of proteopolysaccharide with antitumorigenic activity |
-
1988
- 1988-09-14 JP JP63228848A patent/JPH0278630A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5574797A (en) * | 1978-12-04 | 1980-06-05 | Mitsubishi Yuka Yakuhin Kk | Preparation of protein polysaccharide having anti-tumor activity |
| JPS55108293A (en) * | 1979-02-15 | 1980-08-20 | Mitsubishi Yuka Yakuhin Kk | Production of proteopolysaccharide with antitumorigenic activity |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06239761A (en) * | 1993-02-12 | 1994-08-30 | Hitoshi Ito | Agent for internal use, food and drink having appetite stimulating action |
| FR2721932A1 (en) * | 1994-06-30 | 1996-01-05 | Palmer Research | New glyco-protein from edible mushrooms |
| WO1998027992A1 (en) * | 1996-12-20 | 1998-07-02 | Sumitomo Forestry Co., Ltd. | Antitumor active substances |
| US6093694A (en) * | 1996-12-20 | 2000-07-25 | Sumitomo Forestry Co., Ltd. | Antitumor active substances |
| EP0939082A1 (en) * | 1998-01-16 | 1999-09-01 | Agaricus Laboratories Co., Ltd. | Protein polysaccharide 0041 |
| JP2001240603A (en) * | 2000-02-29 | 2001-09-04 | Toei Shinyaku Kk | beta-1,3-BRANCHED beta-1,6-GLUCAN AND ALKALI EXTRACTED ESSENCE OF AGARICUS MUSHROOM |
| US6627201B2 (en) | 2001-04-03 | 2003-09-30 | Kabushiki Kaisha Sun Chlorella | Composition for drinking/eating and beverage/food |
| JP2007291001A (en) * | 2006-04-24 | 2007-11-08 | Bizen Chemical Co Ltd | New anticancer agent |
| JP2014001188A (en) * | 2012-06-20 | 2014-01-09 | Hiroko Ito | Neovascularization inhibitor, and food and drink composition for inhibiting neovascularization |
| JP2018083807A (en) * | 2016-11-11 | 2018-05-31 | 株式会社岩出菌学研究所 | Anticancer agent tolerance inhibitor having immune checkpoint inhibitory function, and method for producing the same |
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