JPS5910548A - Pfaffic acid and derivative thereof - Google Patents
Pfaffic acid and derivative thereofInfo
- Publication number
- JPS5910548A JPS5910548A JP11887282A JP11887282A JPS5910548A JP S5910548 A JPS5910548 A JP S5910548A JP 11887282 A JP11887282 A JP 11887282A JP 11887282 A JP11887282 A JP 11887282A JP S5910548 A JPS5910548 A JP S5910548A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- puff
- formula
- solvent
- methanol
- 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.)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
この発明は下記の一般式(I)で示される抗腫瘍活性を
有する新規化合物に関する:
1式中、R1は水素原子またはアシル基、R2は水素原
子またはアルキル基を表わす10式(1)において、R
1およびに2か水素である化合物、即ち3β−ヒドロキ
シ−16,20−シクロ−30−フルオレアン−12−
エン−28−オイツクアソツドは、ブラジルニンジン(
Pra[fiapaniculata kuntze
)から単離された全く新規な構造を有する化合物であっ
て、本発明者らによりパフ酸(1’raffic ac
id )と命名された。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel compound having antitumor activity represented by the following general formula (I): In the formula (1), R1 represents a hydrogen atom or an acyl group, and R2 represents a hydrogen atom or an alkyl group. 10 In formula (1), R
Compounds in which 1 and 2 are hydrogen, i.e. 3β-hydroxy-16,20-cyclo-30-fluorene-12-
EN-28-OITSUKU ASSOD is a Brazilian ginseng (
Pra [fiapaniculata kuntze
) is a compound with a completely novel structure isolated from puff acid (1'raffic ac
id).
ブラジルニンジンは南米に自生するヒュ科の多年生植物
で、古くからインディオが民間薬として、滋養、強壮、
強精、鎮静の目的に、あるいは糖尿病、潰瘍、白血病、
癌などの治療に用いて来た。Brazilian ginseng is a perennial plant of the Hull family that grows in South America, and has been used as a folk medicine since ancient times for its nourishing, tonic, and tonic properties.
For energizing, sedative purposes, or for diabetes, ulcers, leukemia,
It has been used to treat cancer, etc.
しかしながら、その有効成分についてはこれまで全く明
らかにされていない。本発明者らは、この有効成分を解
明すべく長年研究を重ねた結果、培養腫瘍細胞の増殖に
対して著しい抑制作用を示す物質を単離することに成功
し、構造解析の結果−その物質が上記パフ酸であること
を見い出した。However, its active ingredients have not been revealed at all so far. As a result of many years of research to elucidate this active ingredient, the present inventors succeeded in isolating a substance that exhibits a remarkable inhibitory effect on the proliferation of cultured tumor cells, and as a result of structural analysis - the substance. was found to be the above puff acid.
更に、本発明者らは、パフ酸をエステル化して得られる
アルキルパフ酸(式(I)において1(2−アルキル基
である化合物)およびアシル化して得られるアシルパフ
酸(式(■)においてlζ1ニアシル基である化合物)
も、パフ酸と同様優れた抗腫瘍活性を有することを見い
出し本発明を完成した。Furthermore, the present inventors have discovered an alkyl puff acid obtained by esterifying puff acid (a compound that is a 1 (2-alkyl group) in formula (I)) and an acyl puff acid obtained by acylating it (a compound that is a 1 (2-alkyl group) in formula (■)). compound that is a group)
The present invention was completed based on the discovery that the same anti-tumor activity as puffed acid has excellent anti-tumor activity.
パフ酸は以下の方法でブラジルニンジンから抽出、単離
することがてきる。即ち、乾燥したブラジルニンジンの
根を粉砕し、アルコールで抽出し、得うれたアルコール
エキスを水に)V濁し、n −フタノールで抽出する。Puff acid can be extracted and isolated from Brazilian ginseng by the following method. That is, the dried Brazilian ginseng root is crushed and extracted with alcohol, and the resulting alcoholic extract is diluted with water and extracted with n-phthanol.
次いてn−ブタノール抽出エキスを水可溶部と難溶部に
分&Jる。後者をシリカゲルカラムクロマトクラフィー
にかけて精製すれば、植物中、遊離の形で含まれている
パフ酸が得られる。一方、上記n−ブタノール抽出エキ
スの水可溶部には、糖と結合したパフ酸(サポニン)が
含まれているので、これを適当な方法で加水分解し、有
機溶媒で抽出した後シリカケルカラムクロマトクラフィ
ーにかけれは、植物中、サポニンの形で含まれているパ
フ酸を得ることができる。Next, the n-butanol extract is divided into a water-soluble part and a poorly soluble part. If the latter is purified by silica gel column chromatography, puff acid, which is present in free form in plants, can be obtained. On the other hand, the water-soluble part of the above n-butanol extract contains puff acid (saponin) bound to sugar, so this is hydrolyzed by an appropriate method, extracted with an organic solvent, and then silica gel is added. Puff acid, which is present in plants in the form of saponin, can be obtained by column chromatography.
」二記のことから明らかな様に、パフ酸自体は水に輔溶
、比較的極性の低い有機溶媒に可溶であり、サポニンは
その逆であるので、抽出溶媒として、アルコールの代り
に水を使用すれば主としてサポニンの形のパフ酸が、ア
セトン、酢酸エチル、クロロホルム、エーテルなどの有
機溶媒を使用すれは主として遊離のパフ酸が得られる。As is clear from the above, puff acid itself is soluble in water and relatively low polar organic solvents, and the opposite is true for saponin, so water is used instead of alcohol as the extraction solvent. If an organic solvent such as acetone, ethyl acetate, chloroform, or ether is used, mainly free puff acid can be obtained.
従って、ブラジルニンジンを水および上記有機溶媒で交
互に抽出すれば全てのパフ酸を抽出することができるが
、実際的見地からはアルコール、特にメタノールで抽出
するのが好ましい。尚、この場合、全てのパフ酸を含有
している前記アルコールエキスを直接加水分解すること
もでき、経済的観点がらはこの方法が最も好ましい。Therefore, although it is possible to extract all the puff acid by extracting Brazilian ginseng alternately with water and the above-mentioned organic solvents, from a practical point of view it is preferred to extract with alcohol, especially methanol. In this case, it is also possible to directly hydrolyze the alcoholic extract containing all puffed acid, and this method is most preferred from an economic standpoint.
サポニンの加水分解には通常の酸またはアルカリを使用
することができるが、予め過ヨウ素酸塩で糖部分を分解
しておけば、比較的緩和な条件下で加水分解することが
できる。もつとも、後述する様にパフ酸はその複雑な構
造にもかかわらず、かなり安定な物質であるので、後者
の加水分解法が特に望ましい訳ではない。尚、このサポ
ニンは、酵素や土壌菌、空中落下細菌などの細菌類で生
化学的に加水分解することもてきる。Normal acids or alkalis can be used to hydrolyze saponins, but if the sugar moiety is decomposed with periodate in advance, hydrolysis can be carried out under relatively mild conditions. However, as described below, puff acid is a fairly stable substance despite its complex structure, so the latter hydrolysis method is not particularly desirable. Note that this saponin can also be biochemically hydrolyzed by enzymes and bacteria such as soil bacteria and airborne bacteria.
上記の方法で得られる粗製のパフ酸は、アルコールから
の再結晶、カラムクロマトクラフィーまたはプレパラテ
イブ薄層クロマトグラフィーなどにより精製することが
できる。The crude puff acid obtained by the above method can be purified by recrystallization from alcohol, column chromatography, preparative thin layer chromatography, or the like.
アルキルパフ酸およびアシルパフ酸は、常法によりパフ
酸から誘導することができる。即ち、前者はアルコール
と脱水剤またはジアゾメタンなどでアルキル化すること
により、後者は酸無水物またはアシルハライドなどてア
シル化することにより容易に製造することができる。Alkyl puff acids and acyl puff acids can be derived from puff acids by conventional methods. That is, the former can be easily produced by alkylating with an alcohol and a dehydrating agent or diazomethane, and the latter can be easily produced by acylating with an acid anhydride or acyl halide.
既述した様に、パフ酸は炭素数29のこれまで全く知ら
れていない特異な骨核を有する酸、アルカリに安定な結
晶性物質であって、その融点は285〜286℃である
。As mentioned above, puff acid is a crystalline substance that is stable to acids and alkalis and has a unique bone core with 29 carbon atoms, which has been completely unknown until now, and its melting point is 285 to 286°C.
パフ酸およびアルキルパフ酸並びに゛Tアシルパフ酸、
マウス由来の黒色腫瘍細胞(メラノーマB]6)、マウ
ス由来の肺癌細胞(3LL)およびヒト由来のγ−宮!
J部癌細胞(l1eLa S 3 )に対して4〜6/
’ K/ /mfの低濃度でその増殖を極めて顕著に抑
制する。Puff acid and alkyl puff acid and T-acyl puff acid,
Mouse-derived melanoma cells (melanoma B) 6), mouse-derived lung cancer cells (3LL), and human-derived γ-miya!
4 to 6/for J region cancer cells (l1eLa S 3 )
' Low concentrations of K//mf inhibit its proliferation quite significantly.
一方、既述した様に、ブラジルニンジンはオヨそ300
年前からインディオによって服用されて来た植物であり
、従ってこの植物成分の毒性が低いことは明らかである
。事実、ブラジルのある病院において、ブラジルニンジ
ンの粉末を1日1〜157内服させた所、何らの副作用
も認められなかったことが報告されている。従って、ブ
ラジルニンジン中に遊離の形で、あるいはサポニン配糖
体として0.1〜1%程度含まれているパフ酸は、少な
くとも通常の使用範囲(10〜〜12/日)においては
、毒性を示さないことは明らかである。On the other hand, as mentioned above, Brazilian carrots are 300
It is a plant that has been used by Indians for many years, so it is clear that the toxicity of this plant component is low. In fact, a hospital in Brazil reported that no side effects were observed when Brazilian ginseng powder was taken orally for 1 to 15 hours a day. Therefore, puffic acid, which is contained in Brazilian ginseng in free form or as a saponin glycoside at about 0.1 to 1%, is not toxic at least within the normal usage range (10 to 12 days). It is clear that it is not shown.
パフ酸の簡単な誘導体であるアルキルパフ酸およびアシ
ルパフ酸も、パフ酸と同様低毒性であることは、当業者
には容易に推測される所である。Those skilled in the art can readily infer that alkyl puff acids and acyl puff acids, which are simple derivatives of puff acid, also have low toxicity like puff acid.
式(I)の化合物を実際の治療に用いるには、これを散
剤、顆粒剤、カプセル剤、液剤などの形で内服させれば
よい。あるいは式(■)の化合物を水に懸濁したり油性
溶剤に溶解し、注射剤または外用剤として使用すること
もできる。尚、パフ酸の代りにパフ酸を高濃度で含有す
る抽出画分、エキスなどを使用して製剤化することもて
きる。In order to use the compound of formula (I) in actual treatment, it may be taken orally in the form of powder, granules, capsules, liquid, or the like. Alternatively, the compound of formula (■) can be suspended in water or dissolved in an oily solvent and used as an injection or external preparation. In addition, instead of puff acid, it is also possible to formulate a formulation using an extracted fraction, extract, etc. containing puff acid at a high concentration.
式(■)の化合物のヒトに於ける投与、量は、症状に応
じて1日当たり約10 mg〜1yとすることがてきる
が、通常too+v/日前後であることが好ましい。The dosage of the compound of formula (■) in humans can be about 10 mg to 1 y per day depending on the symptoms, but it is usually preferably around too+v/day.
以下に実施例を挙けて本発明を史に詳細に説明する。The present invention will be explained in detail below with reference to Examples.
実施例1
乾燥したブラジルニンジンの根を粉砕し、18Kyヲメ
タ/ −/l/200 / テ3回1,11600zで
加熱抽出する。抽出液を減圧で濃縮し、メタノールエキ
ス2に9を得る。このうち8202を水500I+Ie
に懸濁させ、n−ブタノール500 meで常温にて振
とうして抽出、この操作を5回繰り返す。ブタノール層
を集め、減圧で溶媒を留去し、残留物1407を得る。Example 1 Dried Brazilian ginseng roots are crushed and extracted by heating at 1,11600 z for 3 times of 18 Kywometa/-/l/200/te. The extract was concentrated under reduced pressure to obtain methanol extract 2 to 9. Of these, 8202 are water 500I+Ie
The suspension is suspended in water, extracted by shaking with 500 m of n-butanol at room temperature, and this operation is repeated 5 times. The butanol layer is collected and the solvent is distilled off under reduced pressure to obtain residue 1407.
これに水300 mffを加え、攪拌し、遠心分離後、
」二清を除く。さらに、沈澱に水200IIIeを加え
、同様の操作を2度繰り返し、水不溶性の沈澱27yを
得る。上清は別に集める。Add 300 mff of water to this, stir, and after centrifugation,
”Excluding Erqing. Further, water 200IIIe is added to the precipitate and the same operation is repeated twice to obtain a water-insoluble precipitate 27y. Collect the supernatant separately.
この沈澱をクロロホルム−メタノール2:1(7)混液
に溶解し、シリカゲル407と混和し、水浴上で攪拌し
ながら溶剤を完全に蒸発させ、700’i!のシリカゲ
ルのカラム上に置き、ヘキサン、ヘキサン−酢酸エチル
の混液、酢酸エチル、酢酸エチル−メタノールの混液を
用いて順次溶出する。酢酸エチルから酢酸エチJLI−
メタノール20:1の混液の範囲て溶出する画分を集め
、溶剤を留去し、15gの残留物を得る。これを30y
のシリカゲルと混和し、5007のシリカゲルのカラム
の上に置き、クロロホルム−メタノールの混液て溶出す
る。クロロホルム−メタノール50:1〜20:lで溶
出する両分を集め、溶剤を留去し、残留物をメタノール
から再結晶すればパフ酸I FI Oqが無色針状結晶
として得られる。This precipitate was dissolved in a 2:1 (7) mixture of chloroform and methanol, mixed with silica gel 407, and the solvent was completely evaporated while stirring on a water bath. Place the column on a silica gel column and sequentially elute with hexane, a hexane-ethyl acetate mixture, ethyl acetate, and an ethyl acetate-methanol mixture. From ethyl acetate to ethyl acetate JLI-
The fractions eluting in a 20:1 mixture of methanol are collected and the solvent is evaporated to give 15 g of a residue. This is 30y
The mixture is mixed with 5007 silica gel, placed on a 5007 silica gel column, and eluted with a chloroform-methanol mixture. Both fractions eluted with 50:1 to 20:1 of chloroform-methanol are collected, the solvent is distilled off, and the residue is recrystallized from methanol to obtain puff acid I FI Oq as colorless needle-like crystals.
mP 185〜186”C,C(2山、=109.2°
(cm0.72 クロロホルム)、水に不溶、メタノー
ル、エタノール、ピリジン、酢酸エチル、エーテルにi
iJ溶、ベンゼンに難溶、ヘキサンに不溶。リーベルマ
ンバーチヤード反応陽性(紅紫色)、テトラニトロメタ
ン反応陽性(淡微黄色)。IR’、 KRr+11aX
cm :3350.2950 、’28’70.16
90,1460゜1380.1035,995 。 M
S m/z : 440 。mP 185~186”C,C (2 peaks, = 109.2°
(cm0.72 chloroform), insoluble in water, methanol, ethanol, pyridine, ethyl acetate, ether
iJ soluble, sparingly soluble in benzene, insoluble in hexane. Positive Liberman Birchyard reaction (reddish-purple color), positive tetranitromethane reaction (light yellow color). IR', KRr+11aX cm:3350.2950,'28'70.16
90,1460°1380.1035,995. M
S m/z: 440.
422.284,232,207,187,164゜元
素分析(C29”4403として); WI算値:
C179,04;II、 10.06 、実験値:C,
79,32:11、l□、OB、NMRデータは表1お
よび2に示した。422.284,232,207,187,164° Elemental analysis (as C29”4403); WI calculated value:
C179,04; II, 10.06, experimental value: C,
79,32:11, l□, OB, NMR data are shown in Tables 1 and 2.
実施例2
実MAJ1のメタノールエキス68o2にメタノ−7/
Lz3.34−4 N硫酸500−を加え、3時間加熱
還流した後、メタノールを減圧留去し、放冷後、析出す
る沈澱1°60yを沖取する。これをクロロホルム−メ
タノール2:1の混液に溶解し、シリカゲル100yを
加えて混和し、水浴」二で攪拌しISから溶剤を完全に
蒸発させ、5007のソリ力ゲルのカラム」二に置き、
実施例1における水不溶性沈澱の場合と同様に操作し、
パフ酸350 tqを得る。Example 2 Methanol-7/methanol extract 68o2 of real MAJ1
After adding Lz3.34-4 500-4N sulfuric acid and heating under reflux for 3 hours, methanol was distilled off under reduced pressure, and after cooling, the precipitate 1°60y was taken off the water. Dissolve this in a 2:1 mixture of chloroform and methanol, add 100 y of silica gel, mix, stir in a water bath to completely evaporate the solvent from the IS, and place on a column of 5007 siligel.
Operate in the same manner as in the case of water-insoluble precipitate in Example 1,
350 tq of puff acid is obtained.
実施例3
実施例1て得た上清(水ijJ溶部)を集め、カラムク
ロマト用活性炭350gの層を通過さぜ、水500 m
eで洗浄後、エタノール、エタノール−酢酸エチルの混
液、酢酸エチルを用いて順次溶出する。エタノール−酢
酸エチル3ニアから酢酸エチルの範囲で溶出する両分を
集め、溶剤を留去すると淡故褐色の粗製のサポニン粉末
19りが得られる。このサポニン280 mgを2N硫
v50 mFに溶解し、3時間加熱還流後、放冷し、析
出する沈澱を水洗後、メタノールから再結晶し、パフ酸
28myを得る。Example 3 The supernatant obtained in Example 1 (water ijJ solution) was collected, passed through a layer of 350 g of activated carbon for column chromatography, and washed with 500 m of water.
After washing with e, elution is sequentially performed using ethanol, a mixture of ethanol and ethyl acetate, and ethyl acetate. Both eluted fractions ranging from ethanol-ethyl acetate to ethyl acetate are collected and the solvent is distilled off to obtain a pale brown crude saponin powder. 280 mg of this saponin is dissolved in 2N sulfur v50 mF, heated under reflux for 3 hours, allowed to cool, and the precipitate that precipitates is washed with water and recrystallized from methanol to obtain 28 my of puff acid.
実施例4
実施例3で得た粗製のサポニン50〜をメタノール10
mpに溶解し、過ヨウ素酸ナトリウム100mgを加え
、4日間室温で攪拌後、n−ブタ/−ルで3口振とうし
て抽出し、n−ブタノール層を水洗後、溶剤を減圧で留
去する。残留物に5′?I)水酸化カリウム溶液5 m
eを加え、窒素気流中で2時間加熱還流を行なう。反応
物を10%リン酸で中和し、n−ブタ/−ルで振とうし
て抽出し、11−ブタノール層を水洗する。溶剤を減圧
で留去し、得られた残留物をメタノールから再結晶し、
パフ酸12〜を得る。Example 4 50 to 50% of the crude saponin obtained in Example 3 was mixed with 10 to 10% of methanol.
mp, add 100 mg of sodium periodate, stir at room temperature for 4 days, shake and extract with n-butanol for 3 mouths, wash the n-butanol layer with water, and remove the solvent under reduced pressure. do. 5' in the residue? I) Potassium hydroxide solution 5 m
Add e and heat under reflux in a nitrogen stream for 2 hours. The reaction mixture was neutralized with 10% phosphoric acid, extracted by shaking with n-butanol, and the 11-butanol layer was washed with water. The solvent was distilled off under reduced pressure, and the resulting residue was recrystallized from methanol.
Puff acid 12~ is obtained.
実施例5
パフ酸40〜をメタノール5 mlに溶解し、ジアゾメ
タンエーテル溶液を過剰に加え、−夜室温で放置後、溶
剤を減圧で留去し、得られた残留物をメタノールから再
結晶すると無色針状結晶のメチルパフ酸(式(I)にお
いてR1=tl 、 R2= CI+3> 38〜が得
られる。mp 169〜170”Co水に不溶。Example 5 40 ~ of puffic acid was dissolved in 5 ml of methanol, an excess of diazomethane ether solution was added, and after being left at room temperature overnight, the solvent was distilled off under reduced pressure. When the resulting residue was recrystallized from methanol, it became colorless. Acicular crystals of methylpuffic acid (formula (I) with R1=tl, R2=CI+3>38~ are obtained. mp 169~170''Co insoluble in water.
メタノール、エタノール、ピリジン、酢酸エチル、エー
テル、クロロホルム、ベンゼン、ヘキサンに可溶。11
1ν、、、axtyn 、3450,2950.28
70゜1720.1455.13B0,995゜MSm
/z :454.436,298,246,207,1
87,178゜元素分析(C30”4603として);
a1算値:C979,25;o、10.’20 、実験
値:C,78,95;11.10.40゜N M Rデ
ータは表1および2に示した。Soluble in methanol, ethanol, pyridine, ethyl acetate, ether, chloroform, benzene, hexane. 11
1ν,,,axtyn,3450,2950.28
70°1720.1455.13B0,995°MSm
/z :454.436,298,246,207,1
87,178° elemental analysis (as C30”4603);
a1 calculated value: C979, 25; o, 10. '20, Experimental value: C, 78,95; 11.10.40°N MR data are shown in Tables 1 and 2.
実施例6
パフ酸35 Wを無水酢酸−ピリジン1:1の混液6
、/に溶解し、−夜室温で放置後、溶剤を減圧で留去し
、残留物に水5 meを加える。析出する沈澱を沖取し
、含水メタノールから再結晶すると無色針状結晶のアセ
チルパフ酸(式(1)においてR1=c113Go、R
2,,11) 35■が得られる。i叩302〜305
°0水に不溶、メタノール、エタノール、△
ピリジン、酢酸エチル、ベンゼンに可溶、ヘキサンに廁
ト溶。IkVmax−,2950,2870゜1730
.1690,1455,1375,1240゜1021
025o、/y、+ 422,284,232,187
゜】64゜元素分析(C31[I4604として);言
1算値:C,77,14;It、’9.61 、実験値
:C,76,91;11,9.84゜NMRデータは表
1および2に示した。Example 6 Puff acid 35W was mixed with acetic anhydride-pyridine 1:1 mixture 6
,/, and after standing overnight at room temperature, the solvent was distilled off under reduced pressure and 5 me of water was added to the residue. When the precipitate is taken off the coast and recrystallized from water-containing methanol, colorless needle-like crystals of acetylpuffic acid (R1=c113Go, R
2,,11) 35■ is obtained. i hit 302-305
Insoluble in 0 water, soluble in methanol, ethanol, pyridine, ethyl acetate, benzene, soluble in hexane. IkVmax-, 2950, 2870°1730
.. 1690, 1455, 1375, 1240°1021
025o, /y, + 422,284,232,187
゜] 64゜ Elemental analysis (C31 [as I4604); Calculated value: C, 77, 14; It, '9.61, Experimental value: C, 76, 91; 11, 9.84゜ NMR data are shown in 1 and 2.
実施例7
アセチルパフ酸30 rqをメタノール5 meに溶解
し、ジアゾメタンエーテル溶液を過剰に加え、−夜室温
で放置後°、溶剤を減圧で留去し、残留物をメタノール
から再結晶すると無色板状結晶のメチ酢酸エチル、ベン
ゼン、ヘキサンにO■溶、 IR、KRr、l :29
50,2870.1?30,1455゜ax
1370.1270.10301030o/y、: 4
96゜436.298,246,187,178゜元素
分析(C32”4804として);J1算値:C,77
,38゜11.9.74.実験値:C,77,15,I
I、10.00゜NMRデータは表1および2に示した
。Example 7 30 rq of acetyl puffic acid was dissolved in 5 methanol of methanol, an excess of diazomethane ether solution was added, and the solution was left at room temperature overnight. After that, the solvent was distilled off under reduced pressure, and the residue was recrystallized from methanol to give a colorless plate. Crystals of ethyl methacetate, benzene, dissolved in hexane with O, IR, KRr, l: 29
50,2870.1?30,1455゜ax 1370.1270.10301030o/y,: 4
96° 436.298, 246, 187, 178° Elemental analysis (as C32"4804); J1 calculated value: C, 77
,38°11.9.74. Experimental value: C, 77, 15, I
I, 10.00° NMR data are shown in Tables 1 and 2.
実施例8
パフ酸の黒色腫瘍細胞に対する作用
培養液:)IAMの合成培、IIF−10およびり、−
15の3−1混液に牛胎児血清を加えて用いた。血清濃
度は、培養細胞数が最大値の1/2になるような濃度と
した。Example 8 Effect of puff acid on black tumor cells Culture medium:) Synthetic medium of IAM, IIF-10 and Ri, -
A mixture of 15 and 3-1 was used by adding fetal bovine serum. The serum concentration was such that the number of cultured cells was 1/2 of the maximum value.
操作法;パフ酸を」−記の培養液に溶解し、その4.5
rdを径60朋の培養1((lにとり、これにマウス黒
色腫瘍細胞(メラノーマ1316)浮遊培養液0.5
me (細胞数lXl0’個を含む)を加え、4日間、
37°で、5%CO。インキュベーターで培養した後、
培養液を吸引して除き、生理食塩水で洗浄し、0.12
5%トリプシン−11ank’s液Q、5ml!を加え
、培養器に付着した細胞を剥離し、更に9.5mFの生
理食塩水を加えて細胞を懸濁させ、コールタ−カウンタ
ーで細胞数を計測した。結果を表3に示す。パフ酸は6
/’y/ meの濃度で黒色腫瘍細胞の増殖を顕著に
抑制した。Procedure: Dissolve puff acid in the culture solution described in 4.5.
rd to culture 1 ((1) with a diameter of 60 mm, add 0.5 ml of suspension culture of mouse melanoma cells (melanoma 1316) to this.
me (containing 1X10' cells) and incubated for 4 days.
37° and 5% CO. After culturing in an incubator,
Remove the culture medium by aspirating, wash with saline, and add 0.12
5% trypsin-11ank's solution Q, 5ml! was added to detach the cells adhering to the culture vessel, and further 9.5 mF physiological saline was added to suspend the cells, and the number of cells was counted using a Coulter counter. The results are shown in Table 3. puff acid is 6
The proliferation of black tumor cells was significantly inhibited at the concentration of /'y/me.
実施例9
パフ酸の子宮頚部癌細胞に対する作用
ヒト子宮頚部癌細胞(IIeL、a S 3 )を用い
、実施例8と同様に行なった。結果を表4に示す。パフ
酸は4py/meの濃度でヒト子宮頚部癌細胞の増殖を
顕著に抑制した。Example 9 Effect of puff acid on cervical cancer cells The same procedure as in Example 8 was conducted using human cervical cancer cells (IIeL, aS 3 ). The results are shown in Table 4. Puff acid significantly inhibited the proliferation of human cervical cancer cells at a concentration of 4 py/me.
実施例10
マウス肺癌細胞(3LL)を用い、実施例8と同様に行
なった。結果を表5に示す。パフ酸は4719/ me
の濃度で肺癌細胞の増殖を顕著に抑制した。Example 10 The same procedure as in Example 8 was carried out using mouse lung cancer cells (3LL). The results are shown in Table 5. Puff acid is 4719/me
The proliferation of lung cancer cells was significantly inhibited at a concentration of .
実施例11 錠剤
パフ酸20.0y、乳糖49.6F、微結晶セルロース
49.6y、コーンスターチ0.4fおよびステアリン
酸マクネジ7ウム0.4gをよく混合し、打錠機でスラ
ッグを製し、オツシレーターで粗砕、選粒し一顆粒化す
る。この顆粒120.0yを常法に従って打錠し、裸錠
400錠を製造する。1錠(300〜)当たりパフ酸5
0Ingを含有する。Example 11 Tablets 20.0y of puffed acid, 49.6F of lactose, 49.6y of microcrystalline cellulose, 0.4f of cornstarch and 0.4g of macnesium stearate were mixed well, a slug was made using a tablet machine, and an oscillator was used. Coarsely crush, select, and form into granules. This granule (120.0y) is compressed according to a conventional method to produce 400 plain tablets. Puff acid 5 per tablet (300~)
Contains 0 Ing.
実施例12 カプセル剤
パフ酸含有乾燥エキス(実施例2において硫酸加水分解
物を濃縮して析出する沈澱をよく洗浄し、乾燥して製す
る)50.0y(パフ酸5.0y含有)および乳糖50
.OFをよく混合し、カプセル充填機を用いてカプセル
500個を製造する。カプセル1個当りパフ酸10m2
を含有する。Example 12 Capsules Puff acid-containing dry extract (produced by concentrating the sulfuric acid hydrolyzate in Example 2, thoroughly washing the precipitate, and drying) 50.0 y (contains 5.0 y of puff acid) and lactose 50
.. The OF is mixed well and 500 capsules are manufactured using a capsule filling machine. Puff acid 10m2 per capsule
Contains.
表2 13C−NMRppm(C51,)5N
)徳島市西須賀町下中須36−5
0出 願 人 小田島粛夫
金沢車圧上新町328
1沼、“、・r山−t ン14(1介)昭和1)フィロ
−11122rl
′I斜’l IT I;官1讃
L ′−1jl’lの入車
11jt fll !’) 71特泊願第−11J3F
(7?号2 介、明の名称
バノnソお土ひ?の諜戊導1本
3、 ンit it’ f、l ろ11事1)1と
の関係 i、l、 M’l出ii+!′1人(1所 大
阪ni大阪巾生野区巽西1NIJ′i吊1号名称 n−
1・製蘂株式会?1
4、代理人
fl t’li〒h /I ’1
n 、 tni if:命令の1目;1:1介〔i、
補11の拓1象:明IIn円の発明の詳細な説明の1閘
7、?山11の1人l?″ダ
明細i’; ’l D頁目i、l 1llll 1 B
り・ 日3 ti ’(: lるIH+ 7 r’i
、’4 ” 2 RfX”(’? l fJ J i
t ’jV 11、・1゜1] 1Table 2 13C-NMRppm (C51,)5N
) 36-5 Shimonakasu, Nishisuka-cho, Tokushima City 0 Applicant: Nobuo Odajima 328 Kamishinmachi, Kanazawa, 1-numa, 14 (1) Showa 1) Philo-11122rl 'I diagonal'l IT I; Government 1 San L'-1jl'l's entry 11jt flll!') 71 Special Accommodation Application No.-11J3F
(7? No. 2 Kai, Ming's name Bano n So Otohi?'s intelligence guidance 1 book 3, it' f, l ro 11 things 1) Relationship with 1 i, l, M'l out ii+! '1 person (1 location Osaka ni Osaka Kakuno-ku Tatsumi Nishi 1NIJ'i Hanging No. 1 name n-
1. Seihin Co., Ltd.? 1 4, agent fl t'li〒h /I '1 n, tni if: 1st item of command; 1:1 intervention [i,
Supplement 11, Taku 1: Detailed explanation of the invention of Ming II Inyen, 1, 7,? One person on Mt. 11? ``Da details i'';'l D page i, l 1llll 1 B
ri/day 3 ti'(: lruIH+ 7 r'i
,'4 "2 RfX"('? l fJ J i
t'jV 11,・1゜1] 1
Claims (1)
原子またはアルキル基を表わす〕 で示される化合物。 2、 R1およびR2が共に水素原子であり、パフ酸
の名称を有する第1項に記載の化合物。 し式中、R】は水素原子またはアシル基、R2は水素原
子またはアルキル基を表わす〕 で示される化合物を必須成分とする抗腫瘍剤。 〔式中、k□およびR2は水素原子を表わす〕で示され
る化合物をブラジルニンジンから抽出単離する方法であ
って、乾燥したブラジルニンジンの根を粉砕してアルコ
ールで抽出し、該抽出液に硫酸を加えて加熱還流した後
溶媒を留去して得られる残留物をシリカゲル充填カラム
に入れ、クロロホルム/メタノール(50: 1〜20
: ])で溶出される両分から溶媒を留去し、残留物
をアルコールから再結晶することを特徴とする方法。[Scope of Claims] A compound represented by formula 1, in which R1 represents a hydrogen atom or an acyl group, and R2 represents a hydrogen atom or an alkyl group. 2. The compound according to item 1, wherein both R1 and R2 are hydrogen atoms and has the name puff acid. In the formula, R] represents a hydrogen atom or an acyl group, and R2 represents a hydrogen atom or an alkyl group. A method for extracting and isolating the compound represented by the formula [wherein k□ and R2 represent hydrogen atoms] from Brazilian ginseng, in which the dried Brazilian ginseng root is ground and extracted with alcohol, and the extract is added to the After adding sulfuric acid and heating to reflux, the solvent was distilled off, and the resulting residue was placed in a column packed with silica gel and mixed with chloroform/methanol (50: 1-20).
A method characterized by distilling off the solvent from both fractions eluted with : ) and recrystallizing the residue from alcohol.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP11887282A JPS5910548A (en) | 1982-07-07 | 1982-07-07 | Pfaffic acid and derivative thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP11887282A JPS5910548A (en) | 1982-07-07 | 1982-07-07 | Pfaffic acid and derivative thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS5910548A true JPS5910548A (en) | 1984-01-20 |
Family
ID=14747201
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP11887282A Pending JPS5910548A (en) | 1982-07-07 | 1982-07-07 | Pfaffic acid and derivative thereof |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5910548A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5449516A (en) * | 1993-08-12 | 1995-09-12 | Instituto De Medicina Tropical De Sao Paulo | Brazilian ginseng derivatives for treatment of sickle cell symptomatology |
-
1982
- 1982-07-07 JP JP11887282A patent/JPS5910548A/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5449516A (en) * | 1993-08-12 | 1995-09-12 | Instituto De Medicina Tropical De Sao Paulo | Brazilian ginseng derivatives for treatment of sickle cell symptomatology |
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