JPH06256352A - Cyathan derivative and nerve growth factor-production inducer or antifungal agent containing the same as active ingredient - Google Patents
Cyathan derivative and nerve growth factor-production inducer or antifungal agent containing the same as active ingredientInfo
- Publication number
- JPH06256352A JPH06256352A JP5071251A JP7125193A JPH06256352A JP H06256352 A JPH06256352 A JP H06256352A JP 5071251 A JP5071251 A JP 5071251A JP 7125193 A JP7125193 A JP 7125193A JP H06256352 A JPH06256352 A JP H06256352A
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- Japan
- Prior art keywords
- derivative
- growth factor
- nerve growth
- antifungal agent
- compound
- 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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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明は、ハリタケ科( Hydnace
ae )、サンゴハリタケ属( Hericium )のキノコであ
るヤマブシタケ( Hericium erinaceum )の培養菌糸体
中に含まれるシアタン( cyathane )誘導体及びこれを
有効成分とする神経成長因子(NGF)産生誘導剤並び
に抗菌剤に関する。BACKGROUND OF THE INVENTION The present invention relates to Hydaceae (Hydnaceae).
ae), a cyathane derivative contained in the cultured mycelium of Hericium erinaceum, a mushroom of the genus Hericium, and a nerve growth factor (NGF) production inducer and antibacterial agent containing the same .
【0002】[0002]
【従来の技術】従来、キノコの子実体中に含まれる化合
物及びその薬剤効果については複数の報告がある。例え
ば、サルノコシカケ科のキノコであるカワラタケ( Pol
yporusversicolor )の子実体中にはエルゴステロール
誘導体が含まれており、該エルゴステロール誘導体には
肝臓癌細胞に対する殺細胞効果のあることがテトラヘド
ロン( Tetrahedron )39,2779〜2785(1
983)に報告されている。またハラタケ科のキノコで
あるヒメマツタケ( Agaricus blazei )の子実体中に
もエルゴステロール誘導体が含まれており、該エルゴス
テロール誘導体には子宮頸癌細胞に対する殺細胞効果の
あることがフィトケミストリ( Phytochemistry )2
7,2777〜2789(1988)に報告されてい
る。同様のことは特公昭48−6766号公報、特公昭
55−71702号公報、特公昭58−62118号公
報等にも報告されている。2. Description of the Related Art Heretofore, there have been a number of reports on compounds contained in mushroom fruiting bodies and their drug effects. For example, the mushrooms of the Sarcobidae family
The fruiting body of yporus versicolor) contains an ergosterol derivative, and the fact that the ergosterol derivative has a cell-killing effect on liver cancer cells is tetrahedron (Tetrahedron) 39, 2779-2785 (1).
983). The fruiting body of Agaricus blazei, which is a mushroom of the agaricid family, also contains an ergosterol derivative, and the ergosterol derivative has a cell-killing effect on cervical cancer cells. Phytochemistry Two
7, 2777-2789 (1988). The same thing is reported in Japanese Patent Publication No. 48-6766, Japanese Patent Publication No. 55-71702, Japanese Patent Publication No. 58-62118.
【0003】ハリタケ科のキノコであるヤマブシタケに
ついても、該ヤマブシタケの子実体中にはオクタデセン
酸誘導体、イソインドリノン誘導体、フタリド誘導体が
含まれており、これらには子宮頸癌細胞に対する殺細胞
効果のあることが特開平3−157347、特開平3−
157367、特開平3−157379に報告されてい
る。[0003] As for the mushrooms of the mushroom mushrooms, the fruiting bodies of the mushrooms also include octadecenoic acid derivatives, isoindolinone derivatives and phthalide derivatives, which have a cytocidal effect on cervical cancer cells. There are some cases in JP-A-3-157347 and JP-A-3-157347.
157367 and JP-A-3-157379.
【0004】[0004]
【発明が解決しようとする課題】しかし、ヤマブシタケ
の培養菌糸体中に含まれる化合物及びその薬剤効果につ
いては全く報告がない。However, there are no reports on the compounds contained in the cultured mycelium of Pleurotus cornucopiae and their drug effects.
【0005】[0005]
【課題を解決するための手段】しかして本発明者らは、
叙上の如き実情に鑑み、ヤマブシタケの培養菌糸体中に
含まれる化合物及びその薬剤効果について鋭意研究した
結果、ヤマブシタケの培養菌糸体中には特定の化学構造
からなる新規のシアタン( cyathane )誘導体が含まれ
ており、該シアタン( cyathane )誘導体には神経成長
因子(NGF)産生誘導効果及び抗菌効果のあることを
見出した。However, the present inventors have
In light of the above-mentioned circumstances, as a result of diligent research on compounds contained in cultured mycelium of Yamabushitake and its drug effect, a new cyathane derivative having a specific chemical structure was found in the cultured mycelium of Yamabushitake. It was found that the cyathane derivative contained therein has a nerve growth factor (NGF) production inducing effect and an antibacterial effect.
【0006】すなわち本発明は、下記の式1で示される
シアタン( cyathane )誘導体及び該シアタン( cyath
ane )誘導体を有効成分とする神経成長因子(NGF)
産生誘導剤並びに抗菌剤に係る。That is, the present invention provides a cyathane derivative represented by the following formula 1 and the cyathane derivative.
nerve growth factor (NGF) containing ane) derivative as an active ingredient
It relates to production inducers and antibacterial agents.
【0007】[0007]
【式1】 [Formula 1]
【0008】式1で示されるシアタン( cyathane )誘
導体はヤマブシタケの菌糸体を次のように処理すること
によって得られる。先ず、ヤマブシタケの菌糸体をSG
C培地(グルコース、スターチ、コーンスティープリカ
ー、KH2PO4、CuSO4、ZnCl2、塩酸チアミン
及び水系のPH=5.3〜5.5に調製された液体培
地)にて30℃で4週間培養する。得られた培養菌糸体
を遠心分離によって上澄液と沈殿物である培養菌糸体と
に分離し、該培養菌糸体を水及び有機溶媒の均一系で抽
出する。この場合、水及び有機溶媒の均一系としては、
80〜85%メタノールやエタノール、85%アセトン
等がある。抽出は通常室温で行なうが、加熱還流しても
よく、抽出時間は通常1〜72時間である。例えば、8
5%エタノール中にヤマブシタケの培養菌糸体を加え、
ホモジナイズ処理し、これを室温で一昼夜放置した後、
濾過して抽出液を得、該抽出液を減圧下に40〜45℃
で加熱して有機溶媒を蒸発することにより水相を得るの
である。The cyathane derivative represented by the formula 1 can be obtained by treating the mycelium of Pleurotus cornucopiae as follows. First, the mycelium of Yamabushitake is SG
C medium (a liquid medium prepared by adjusting glucose, starch, corn steep liquor, KH 2 PO 4 , CuSO 4 , ZnCl 2 , thiamine hydrochloride and aqueous PH = 5.3 to 5.5) at 30 ° C. for 4 weeks Incubate. The obtained cultured mycelium is separated into a supernatant and a cultured mycelium that is a precipitate by centrifugation, and the cultured mycelium is extracted with a homogeneous system of water and an organic solvent. In this case, as a homogeneous system of water and organic solvent,
80-85% methanol, ethanol, 85% acetone and the like. The extraction is usually performed at room temperature, but may be heated under reflux, and the extraction time is usually 1 to 72 hours. For example, 8
Add the mycelium of Yamabushitake culture to 5% ethanol,
After homogenizing and letting this stand at room temperature for a whole day and night,
The extract is obtained by filtration, and the extract is under reduced pressure at 40 to 45 ° C.
The aqueous phase is obtained by heating at to evaporate the organic solvent.
【0009】次に、該水相を水及び有機溶媒の混合系で
液−液分配抽出処理して有機溶媒層を分取し、該有機溶
媒層から有機溶媒を蒸発して乾固物を得る。この場合、
有機溶媒としては、クロロホルム、酢酸エチル、ジエチ
ルエーテル等がある。例えば、上記水相に酢酸エチルを
加え、振盪後、放置して分層した酢酸エチル層を分取
し、該酢酸エチル層を減圧下に40〜45℃で加熱して
酢酸エチルを蒸発することにより乾固物を得るのであ
る。Next, the aqueous phase is subjected to a liquid-liquid partition extraction process with a mixed system of water and an organic solvent to separate an organic solvent layer, and the organic solvent is evaporated from the organic solvent layer to obtain a dry matter. . in this case,
Examples of the organic solvent include chloroform, ethyl acetate, diethyl ether and the like. For example, ethyl acetate is added to the above aqueous phase, after shaking, the ethyl acetate layer separated by standing is separated, and the ethyl acetate layer is heated under reduced pressure at 40 to 45 ° C. to evaporate the ethyl acetate. To obtain a dry solid.
【0010】上記乾固物はそれ自体が神経成長因子(N
GF)産生誘導剤及び抗菌剤として有効なものである
が、該乾固物から不純物を除去してその神経成長因子
(NGF)産生誘導効果及び抗菌効果を高めるために、
該乾固物をクロマト分画処理するのが好ましく、クロマ
ト分画処理したものを更に再分画処理して目的とするシ
アタン( cyathane )誘導体を単離するのがより好まし
い。この場合、詳しくは実施例で後述するように、クロ
ロホルム/アセトン、ヘキサン/エーテル等を展開溶媒
とするシリカゲルカラムクロマトグラフィー或は薄層ク
ロマトグラフィーを用いてクロマト分画処理することが
でき、またODSカラムを用いた高速液体クロマトグラ
フィーで再分画処理することができる。The dry matter itself is a nerve growth factor (N
It is effective as a GF) production inducer and an antibacterial agent, but in order to remove impurities from the dried solid matter to enhance its nerve growth factor (NGF) production inducing effect and antibacterial effect,
It is preferable to subject the dried solid matter to a chromatographic fractionation, and it is more preferable to further subject the chromatographically fractionated product to a re-fractionation treatment to isolate the desired cyathane derivative. In this case, as will be described later in detail in the Examples, it can be subjected to chromatographic fractionation using silica gel column chromatography or thin layer chromatography using chloroform / acetone, hexane / ether, etc. as a developing solvent, and ODS. Re-fractionation can be performed by high performance liquid chromatography using a column.
【0011】かくして再分画処理することにより単離さ
れる化合物の物理化学的性質及び構造解析結果は下記の
通りである。 (1)分子量:432(C25H36O6) (2)赤外線吸収スペクトル:3421,1691,1
616cm-1 (3)核磁気共鳴スペクトル(1H−NMR,δ):0.
97(3H,d,J=6.59),0.98(3H,
d,J=6.23),0.99(3H,s),1.02
(3H,s),1.50(2H,m),1.53(2
H,m),1.58(2H,m),2.28(3H,
m),2.75(2H,m),3.20(1H,dd,
J=8.42,8.79),3.35(1H,dd,J
=11.72,10.62),3.60(1H,dd,
J=8.79,8.79),3.69(1H,m),
3.82(1H,d,J=9.71),4.03(1
H,dd,J=11.72,5.86),4.58(1
H,d,J=8.42),5.14(1H,d,J=
9.71),6.92(1H,br.s),9.56
(1H,s) (4)核磁気共鳴スペクトル(13C−NMR,δ):1
6.4,21.4,21.9,24.4,27.1,2
7.7,28.4,29.7,36.4,38.1,4
1.6,41.9,49.4,66.9,70.7,7
0.9,71.1,74.9,79.1,98.5,1
35.9,140.2,142.1,155.4,19
3.4 (5)溶媒に対する溶解性:クロロホルム、アセトン、
酢酸エチル、メタノールに可溶、エタノールにやや可
溶、水に不溶 (6)塩基性、中性、酸性の区別:中性物質 (7)色及び性状:無色油状The physicochemical properties and the results of structural analysis of the compound thus isolated by the re-fractionation treatment are as follows. (1) Molecular weight: 432 (C 25 H 36 O 6 ) (2) Infrared absorption spectrum: 3421, 1691, 1
616 cm -1 (3) Nuclear magnetic resonance spectrum ( 1 H-NMR, δ): 0.
97 (3H, d, J = 6.59), 0.98 (3H,
d, J = 6.23), 0.99 (3H, s), 1.02
(3H, s), 1.50 (2H, m), 1.53 (2
H, m), 1.58 (2H, m), 2.28 (3H,
m), 2.75 (2H, m), 3.20 (1H, dd,
J = 8.42, 8.79), 3.35 (1H, dd, J
= 11.72, 10.62), 3.60 (1H, dd,
J = 8.79, 8.79), 3.69 (1H, m),
3.82 (1H, d, J = 9.71), 4.03 (1
H, dd, J = 11.72, 5.86), 4.58 (1
H, d, J = 8.42), 5.14 (1H, d, J =
9.71), 6.92 (1H, br.s), 9.56
(1H, s) (4) Nuclear magnetic resonance spectrum ( 13 C-NMR, δ): 1
6.4, 21.4, 21.9, 24.4, 27.1, 2
7.7, 28.4, 29.7, 36.4, 38.1, 4
1.6, 41.9, 49.4, 66.9, 70.7, 7
0.9, 71.1, 74.9, 79.1, 98.5, 1
35.9, 140.2, 142.1, 155.4, 19
3.4 (5) Solubility in solvent: chloroform, acetone,
Ethyl acetate, soluble in methanol, slightly soluble in ethanol, insoluble in water (6) Distinction between basic, neutral, and acidic: neutral substance (7) Color and properties: colorless oil
【0012】上記の物理化学的性質及び構造解析結果か
ら、単離される化合物は式1で示されるシアタン( cya
thane )誘導体であることが決定された。From the above physicochemical properties and the results of structural analysis, the isolated compound is represented by the formula 1
thane) was determined to be a derivative.
【0013】詳しくは実施例で後述するように、本発明
のシアタン( cyathane )誘導体は神経成長因子(NG
F)産生誘導効果及び抗菌効果があり、神経成長因子
(NGF)産生誘導効果を有する化合物は老人性痴呆症
治療剤としての利用が注目されており、また抗菌効果を
有する化合物は天然抗菌剤として食品への利用が注目さ
れている。As will be described later in detail in Examples, the cyathane derivative of the present invention is a nerve growth factor (NG).
F) A compound having a production-inducing effect and an antibacterial effect and having a nerve growth factor (NGF) production-inducing effect has been attracting attention as a therapeutic agent for senile dementia, and a compound having an antibacterial effect is used as a natural antibacterial agent. Attention has been paid to its use for food.
【0014】[0014]
シアタン( cyathane )誘導体の抽出及び単離 ヤマブシタケの菌糸体をSGC培地(前掲のもの)にて
4週間培養し、培養菌糸体を得た。85%エタノール1
リットルに該培養菌糸体110g(湿重量)を加え、ホ
モジナイズ処理し、これを室温で一昼夜放置した後、濾
過して抽出液を得た。残渣に85%エタノール1リット
ルを加え、同様に抽出処理を行なって抽出液を得、これ
を1回目の抽出液と合わせた。そして合わせた抽出液を
減圧下に40〜45℃で加熱してエタノールを蒸発する
ことにより水相を得た。Extraction and isolation of cyathane derivative The mycelium of Pleurotus cornucopiae was cultured in SGC medium (previously described) for 4 weeks to obtain a cultured mycelium. 85% ethanol 1
110 g (wet weight) of the cultured mycelium was added to 1 liter, homogenized, allowed to stand at room temperature for 24 hours, and then filtered to obtain an extract. To the residue was added 1 liter of 85% ethanol and the same extraction treatment was performed to obtain an extract, which was combined with the first extract. Then, the combined extracts were heated at 40 to 45 ° C. under reduced pressure to evaporate ethanol to obtain an aqueous phase.
【0015】上記水相に酢酸エチル1リットルを加え、
振盪後、放置して分層した酢酸エチル層を分取した。残
渣に酢酸エチル1リットルを加え、同様に液−液分配抽
出処理を行なって酢酸エチル層を分取し、1回目の酢酸
エチル層と合わせた。合わせた酢酸エチル層を減圧下に
40〜45℃で加熱して酢酸エチルを蒸発し、更にデシ
ケータで乾燥して乾固物2.1gを得た。1 liter of ethyl acetate was added to the above aqueous phase,
After shaking, the mixture was allowed to stand and the separated ethyl acetate layer was separated. Ethyl acetate (1 liter) was added to the residue, and liquid-liquid partition extraction processing was performed in the same manner to separate the ethyl acetate layer and combine it with the first ethyl acetate layer. The combined ethyl acetate layers were heated under reduced pressure at 40 to 45 ° C. to evaporate ethyl acetate, and further dried with a desiccator to obtain 2.1 g of a dry solid.
【0016】上記乾固物をヘキサンで溶解し、ワコーゲ
ルC−200(和光純薬社製)を用いてカラムクロマト
グラフィーを行なった。この際、展開溶媒として、順次
極性が大きくなるように、クロロホルム/アセトン=
9:1、8:2、7:3、1:1を各60ml用い、10
mlの画分を合計24画分得た。このうちのクロロホルム
/アセトン=9:1溶出画分を更にシリカゲルカラムク
ロマトグラフィーに供し、展開溶媒としてクロロホルム
/アセトン=7:3を80ml用い、10mlの画分を合計
8画分得た。このうちの第2画分から式1に示されるシ
アタン( cyathane )誘導体を31.9mg単離した。The dried product was dissolved in hexane and subjected to column chromatography using Wakogel C-200 (manufactured by Wako Pure Chemical Industries, Ltd.). At this time, as a developing solvent, chloroform / acetone =
Using 9: 1, 8: 2, 7: 3, 1: 1 60 ml each, 10
A total of 24 fractions of ml were obtained. The fraction eluted with chloroform / acetone = 9: 1 was further subjected to silica gel column chromatography, and 80 ml of chloroform / acetone = 7: 3 was used as a developing solvent to obtain a total of 8 fractions of 10 ml. From the second fraction, 31.9 mg of the cyathane derivative represented by the formula 1 was isolated.
【0017】シアタン( cyathane )誘導体の神経成長
因子(NGF)産生誘導効果 古川らの方法{バイオケミカル アンド バイオフィジ
カル リサーチ コミュニケーションズ( Biochemical
and Biophysical Research Communications),13
6,57−63(1986)}にしたがい、胎生後期
(19日令)ラット皮質初代アストログリア細胞を培養
器に10%牛胎仔血清を含むダルベッコ変法イーグル培
地(DMEM)で培養(1〜2週間、3日毎に培地を交
換)し、コンフルエントに達したところで、0.5%牛
血清アルブミンを含むDMEMに変えて数日培養した。
ここへジメチルスルホキシド(DMSO)に溶解したシ
アタン( cyathane )誘導体を所定濃度になるように
0.5%牛血清アルブミンを含むDMEMにて調製し、
投与した。24時間の培養後、培養液を集め、古川らの
方法{ジャーナル オブ ニューロケミストリー( Jou
rnal of Neurochemistry),40,734−744(1
983)}によるエンザイムアッセイ法で神経成長因子
(NGF)濃度を測定した。シアタン( cyathane )誘
導体を投与しないで培養した対照群とシアタン( cyath
ane )誘導体を1mM投与して培養した群との間でt検
定を行なった。その結果、投与した群は1%の危険率で
有効と有意検定された。Nerve growth factor (NGF) production-inducing effect of cyathane derivatives Furukawa et al.'S method {Biochemical and Biophysical Research Communications
and Biophysical Research Communications), 13
6, 57-63 (1986)}, and cultured in early incubator (19-day-old) rat cortical astroglial cells in a Dulbecco's modified Eagle medium (DMEM) containing 10% fetal bovine serum (1-2 The medium was replaced every 3 days for a week), and when confluent was reached, the medium was changed to DMEM containing 0.5% bovine serum albumin and cultured for several days.
Here, a cyathane derivative dissolved in dimethyl sulfoxide (DMSO) was prepared with DMEM containing 0.5% bovine serum albumin to a predetermined concentration,
Was administered. After culturing for 24 hours, the culture solution was collected and the method of Furukawa et al. {Journal of Neurochemistry (Jou
rnal of Neurochemistry), 40, 734-744 (1
983)}, the nerve growth factor (NGF) concentration was measured by the enzyme assay method. Control group and cyathane (cyathane) cultured without administration of cyathane derivative
An ane) derivative was administered at 1 mM, and a t-test was carried out with a group cultured. As a result, the administered group was significantly tested as effective at a risk rate of 1%.
【0018】シアタン( cyathane )誘導体の抗菌効果 肉エキス1.0%、ポリペプトン0.5%、塩化ナトリ
ウム10.25%、寒天1.5%を含むPH7.2〜
7.4の普通寒天培地を作成し、試験管に15ml及び6
mlずつを分注し、オートクレーブ(121℃で20分)
にて加圧蒸気滅菌を行なった。滅菌済みのシャーレに加
圧蒸気滅菌した15mlの培地を無菌的に流入し、平面に
固定させ基層とした。別に加圧蒸気滅菌した6mlの培地
を溶解し、55〜60℃まで冷却したものに、5mlの液
体培地中で30℃で16時間振盪培養した細菌(バチル
ス ズブチリス)、酵母(サッカロマイセス セレビジ
ェ)、カビ(アスペルギルス ニガー)を50μl接種
し、よく混合した後、これを菌層として上記基層の上に
流入し、検定用培地とした。該検定用培地の上に、シア
タン( cyathane )誘導体の10mg/ml溶液を染み込ま
せて溶媒を乾かしたペーパーディスクを静かにピンセッ
トで乗せ、30℃の恒温室で24時間培養後、生成した
阻止円の直径を測定し、下記の式2により抗菌活性を求
めた。Antibacterial effect of cyathane derivative PH7.2 containing meat extract 1.0%, polypeptone 0.5%, sodium chloride 10.25%, agar 1.5%
Make 7.4 normal agar medium and put 15 ml and 6 in a test tube.
Dispense each ml and autoclave (20 minutes at 121 ℃)
Was sterilized by autoclaving. 15 ml of a medium subjected to pressure steam sterilization was aseptically flown into a sterilized petri dish and fixed on a flat surface to form a base layer. Separately, 6 ml of a medium sterilized by autoclaving was dissolved, cooled to 55-60 ° C, and cultured in 5 ml of liquid medium at 30 ° C for 16 hours with shaking (bacillus subtilis), yeast (Saccharomyces cerevisiae), mold. (Aspergillus niger) was inoculated in an amount of 50 μl and mixed well, and this was used as a fungal layer and flowed onto the above-mentioned base layer to obtain an assay medium. On the assay medium, a 10 mg / ml solution of a cyathane derivative was soaked in a solution and a paper disk dried with a solvent was gently placed with tweezers, and incubated for 24 hours in a thermostatic chamber at 30 ° C. Was measured, and the antibacterial activity was calculated by the following formula 2.
【式2】 抗菌活性(mm)=測定した阻止円の直径(mm)−ペーパ
ーディスクの直径(8mm) 抗菌活性は、細菌(バチルス ズブチリス)に対して1
0mm、酵母(サッカロマイセス セレビジェ)に対して
2mm、カビ(アスペルギルス ニガー)に対して4mmで
あり、シアタン( cyathane )誘導体はこれらの細菌、
酵母、カビに対して抗菌効果のあることが検定された。[Formula 2] Antibacterial activity (mm) = measured diameter of inhibition circle (mm) -diameter of paper disc (8 mm) Antibacterial activity is 1 against bacteria (Bacillus subtilis).
0 mm, 2 mm for yeast (Saccharomyces cerevisiae), and 4 mm for mold (Aspergillus niger), and the cyathane derivative is these bacteria,
It was tested that it had an antibacterial effect against yeast and mold.
【0019】[0019]
【発明の効果】既に明らかなように、以上説明した本発
明のシアタン( cyathane )誘導体には神経成長因子
(NGF)産生誘導剤及び抗菌剤として有効という効果
がある。As is apparent, the cyathane derivative of the present invention described above is effective as a nerve growth factor (NGF) production inducer and an antibacterial agent.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 坂本 秀樹 栃木県那須郡西那須野町井口47番地12 (72)発明者 石黒 幸雄 栃木県那須郡西那須野町東三島5丁目96番 地19 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Hideki Sakamoto 47 Iguchi, Nishinasuno-cho, Nasu-gun, Tochigi 12 12 (72) Yukio Ishiguro 5-96 Higashimishima, Nishinasuno-cho, Nasu-gun, Tochigi 19
Claims (3)
ane )誘導体。 【式1】 1. A cyanate represented by the following formula 1 (cyath
ane) derivatives. [Formula 1]
誘導体を有効成分とする神経成長因子(NGF)産生誘
導剤。2. The cyathane according to claim 1.
A nerve growth factor (NGF) production inducer containing a derivative as an active ingredient.
誘導体を有効成分とする抗菌剤。3. The cyathane according to claim 1.
An antibacterial agent containing a derivative as an active ingredient.
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5071251A JP2657883B2 (en) | 1993-03-04 | 1993-03-04 | Sheatan derivative, nerve growth factor production inducer containing the same as active ingredient, and antibacterial agent |
US08/196,049 US5391544A (en) | 1993-03-04 | 1994-02-10 | Cyathane derivatives and antimicrobial agents containing same |
AT94301549T ATE153340T1 (en) | 1993-03-04 | 1994-03-03 | CYATHANE DERIVATIVES AND THESE CONTAINING NERVE GROWTH FACTOR PRODUCTION STIMULATORS AND ANTIMICROBIAL AGENTS |
DE69403242T DE69403242T2 (en) | 1993-03-04 | 1994-03-03 | Cyathane derivatives and nerve growth factor containing them produce stimulators and antimicrobial agents |
ES94301549T ES2104272T3 (en) | 1993-03-04 | 1994-03-03 | DERIVATIVES OF CIATANO AND STIMULATORS OF THE PRODUCTION OF NERVOUS GROWTH FACTOR AND ANTIMICROBIAL AGENTS THAT CONTAIN THEM. |
EP94301549A EP0613903B1 (en) | 1993-03-04 | 1994-03-03 | Cyathane derivatives and production stimulators of nerve growth factors and antimicrobial agents containing same |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5071251A JP2657883B2 (en) | 1993-03-04 | 1993-03-04 | Sheatan derivative, nerve growth factor production inducer containing the same as active ingredient, and antibacterial agent |
US08/196,049 US5391544A (en) | 1993-03-04 | 1994-02-10 | Cyathane derivatives and antimicrobial agents containing same |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH06256352A true JPH06256352A (en) | 1994-09-13 |
JP2657883B2 JP2657883B2 (en) | 1997-09-30 |
Family
ID=26412373
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Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP5071251A Expired - Fee Related JP2657883B2 (en) | 1993-03-04 | 1993-03-04 | Sheatan derivative, nerve growth factor production inducer containing the same as active ingredient, and antibacterial agent |
Country Status (1)
Country | Link |
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JP (1) | JP2657883B2 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003007977A1 (en) * | 2001-07-16 | 2003-01-30 | Takara Bio Inc. | Remedies |
JP2005239669A (en) * | 2004-02-27 | 2005-09-08 | Yukito Akiyama | Cyathane derivative and antibacterial agent containing the derivative as active component |
JP2005272346A (en) * | 2004-03-24 | 2005-10-06 | Otsuka Bebareji Kk | New compound contained in hericium erinaceum and anti-methicillin-resistant staphylococcus aureus agent |
-
1993
- 1993-03-04 JP JP5071251A patent/JP2657883B2/en not_active Expired - Fee Related
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003007977A1 (en) * | 2001-07-16 | 2003-01-30 | Takara Bio Inc. | Remedies |
JP2005239669A (en) * | 2004-02-27 | 2005-09-08 | Yukito Akiyama | Cyathane derivative and antibacterial agent containing the derivative as active component |
JP4551993B2 (en) * | 2004-02-27 | 2010-09-29 | 幸仁 秋山 | Sheatan derivative and antibacterial agent comprising this as an active ingredient |
JP2005272346A (en) * | 2004-03-24 | 2005-10-06 | Otsuka Bebareji Kk | New compound contained in hericium erinaceum and anti-methicillin-resistant staphylococcus aureus agent |
JP4606048B2 (en) * | 2004-03-24 | 2011-01-05 | 大塚食品株式会社 | Novel compounds and anti-methicillin-resistant Staphylococcus aureus agents in Yamabushitake |
Also Published As
Publication number | Publication date |
---|---|
JP2657883B2 (en) | 1997-09-30 |
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