JPH04128225A - Antitumor agent - Google Patents
Antitumor agentInfo
- Publication number
- JPH04128225A JPH04128225A JP24037890A JP24037890A JPH04128225A JP H04128225 A JPH04128225 A JP H04128225A JP 24037890 A JP24037890 A JP 24037890A JP 24037890 A JP24037890 A JP 24037890A JP H04128225 A JPH04128225 A JP H04128225A
- Authority
- JP
- Japan
- Prior art keywords
- antitumor agent
- active ingredient
- cancer
- carcinogenesis
- 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.)
- Pending
Links
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- 238000000034 method Methods 0.000 abstract description 7
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- 239000000243 solution Substances 0.000 description 2
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- 230000005748 tumor development Effects 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
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- 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 1
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- 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 1
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Landscapes
- Furan Compounds (AREA)
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Abstract
Description
【発明の詳細な説明】
（イ）産業上の利用分野
この発明は、抗腫瘍剤に関する。より詳しくは、この発
明は２−０−アルキルアスコルビン酸またはその塩から
なる抗腫瘍剤に関する。DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application This invention relates to an antitumor agent. More specifically, the present invention relates to an antitumor agent comprising 2-0-alkylascorbic acid or a salt thereof.
（ロ）従来の技術と発明が解決すべき課題従来、ヒトの
悪性腫瘍を治療するためにアルキル化剤、代謝拮抗物資
、抗生物質などが用いられているが、一方では生体に対
する重篤な副作用のため治療を中止せざるを得ない事例
が多々ある。(b) Problems to be solved by conventional techniques and inventions Conventionally, alkylating agents, antimetabolites, antibiotics, etc. have been used to treat human malignant tumors, but on the other hand, they cause serious side effects on living organisms. There are many cases where treatment has to be discontinued.
一方、発癌メカニズムについて種々の研究がなされ、発
癌過程には起始（Ｉｎｉｔｉａｔｉｏｎ）と促進（ｐｒ
ｏａｏｔ １ｏｎ）の二つに分けて考えるのが大勢を占
めている。On the other hand, various studies have been conducted on carcinogenic mechanisms, and the carcinogenic process involves initiation and promotion.
Most people think of it in two parts: oaot 1on).
この二つの過程の何れかを阻害すれば発癌を阻止できる
ことになるが、起始に関与する物質は癌の種類により異
なることが考えられ、一方促進に関与する物質は起姶関
与物質はど多様性がないと考えられている。従って促進
に関与する物質の活性を阻害する物質の出現がより望ま
しいといえる。If either of these two processes is inhibited, carcinogenesis can be prevented, but the substances involved in the initiation are thought to differ depending on the type of cancer, while the substances involved in the promotion are diverse. It is considered to have no sex. Therefore, it would be more desirable to develop a substance that inhibits the activity of the substance involved in promotion.
発癌の過程、とりわけ促進過程は複雑であるが、本発明
者らは細胞の凝集現象に基づく促進に関与する物質の活
性阻害物質の検索系を確立し、報告している［キャンサ
ー・リサーチ（ＣａｎｃｅｒＲｅｓｅａｒｃｈ）、 ４
１．４７０２−４７０５ （Ｉ９８１） ；ガン（Ｊｐ
ｎ。Although the process of carcinogenesis, especially the promotion process, is complex, the present inventors have established and reported a search system for inhibitors of the activity of substances involved in promotion based on the phenomenon of cell aggregation [Cancer Research ), 4
1.4702-4705 (I981); Gan (Jp
n.
Ｊ、 Ｃａｎｃｅｒ Ｒｅｓ、）、 ７９．２３１−２
３５ （Ｉ９８Ｂ） ］。J, Cancer Res, ), 79.231-2
35 (I98B)].
発明者らはこの検索系を用いて種々の薬剤を検討した結
果、２−０−アルキルアスコルビン酸が発癌過程の中で
特に促進の段階で、促進に関与する物質（プロモーター
）の活性の阻富作用を示し、かつ殆ど副作用を示さない
物質であることを見出し、この発明を完成した。As a result of examining various drugs using this search system, the inventors found that 2-0-alkylascorbic acid inhibits the activity of a substance (promoter) involved in carcinogenesis, especially at the promotion stage. This invention was completed after discovering that the substance is effective and exhibits almost no side effects.
なお、２−０−アルキルアスコルビン酸は、循環系機能
障害改善剤として（特開昭６１−２６３９６９号公報参
照）、また白内障治療剤として（特開昭６３−３０１８
１８公報参照）それぞれ知られて（する。In addition, 2-0-alkyl ascorbic acid is used as a circulatory system dysfunction improving agent (see JP-A No. 61-263969) and as a cataract treatment agent (see JP-A No. 63-3018).
(see Publication No. 18).
（ハ）ｍ題を解決するための手段
この発明によれば、式（Ｉ）
％式％
（式中、
ＲはＣ１〜Ｃ□のアルキル基を表わす）で示される２−
０−アルキルアスコルビン酸または医薬的に受容な塩を
有効成分として含有することからなる抗腫瘍剤が提供さ
れる。(c) Means for solving problem m According to the present invention, 2-
An antitumor agent containing 0-alkylascorbic acid or a pharmaceutically acceptable salt as an active ingredient is provided.
上記式において、ＲのＣ１〜Ｃ！ｔのアルキル基として
は、直鎖状または分枝状のアルキル基が挙げられ、とり
わけＣ８゜〜Ｃ２゜の直鎖アルキルであることが好まし
い。その例としては、例えばｎ −ノニル、ｎ−デシル
、ｎ−ウンデシル、ｎ−ドデシル、ｎ−トリデシル、ｎ
−テトラデシル、ｎ−ペンタデシル、ｎ−ヘキサデシル
、ｎ−ヘプタデシル、ｎ−オクタデシル、ｎ−ノナデシ
ル、ｎ−エイコシル、ｎ−ヘネイコシル、ｎ−トコシル
、イソノニルなどが挙げられる。これらの中では特に好
ましいのは、ｎ−オクタデシル基である。In the above formula, C1 to C! of R! Examples of the alkyl group for t include straight-chain or branched alkyl groups, with C8° to C2° straight-chain alkyl being particularly preferred. Examples include n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-
-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecyl, n-eicosyl, n-heneicosyl, n-tocosyl, isononyl, and the like. Among these, particularly preferred is n-octadecyl group.
この発明の医薬的に受容な塩としては、ナトリウム、カ
リウムなどのアルカリ金属塩、カルシウム、マグネシウ
ムなどのアルカリ土類金属塩などが挙げられる。Pharmaceutically acceptable salts of this invention include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, and the like.
また、化合物（Ｉ）は光学異性体としてＤ体、Ｌ体が存
在し、これらの混合物としても存在するが、とりわけＬ
体であることが望ましい。In addition, compound (I) exists as optical isomers of D-form and L-form, and also exists as a mixture of these, but especially L-form.
Preferably the body.
なお、化合物（Ｉ）の製造法、物理化学的性状等につい
てはＥＰＣ公開特許公報第０１４６１２１号に詳細に記
載されている。The manufacturing method, physicochemical properties, etc. of compound (I) are described in detail in EPC Publication No. 0146121.
この発明の有効成分は、毒性が低い。たとえば代表的な
有効成分である２−０−オクタデジルアスコルビン酸に
ついて、マウス経口投与でのＬ Ｄ ｓ。The active ingredients of this invention have low toxicity. For example, the L D s of 2-0-octadecyl ascorbic acid, a typical active ingredient, when administered orally to mice.
は約４０００ｘ９／Ｋｇで、マウスの腹腔内投与のＬＤ
ｓｓは約２００１ｆ／ｌｃｇである。is approximately 4000x9/Kg, which is the LD for intraperitoneal administration in mice.
ss is approximately 2001f/lcg.
この発明の有効成分は、通常、薬理学的に許容される担
体もしくは賦形剤とともに経口または非経口的に投与さ
れる。The active ingredient of this invention is usually administered orally or parenterally together with a pharmacologically acceptable carrier or excipient.
投与量は、癌の種類や進行状態、患者の体重、予防目的
、治療目的などによって変動する。しかし、たとえば治
療目的での経口投与量は、約０．０１〜１００ｍ１！／
Ｋｇ／ｌ〜３回／日である。とりわけ、約０．１〜５０
ｘｙ／ロ／ｌ〜３回７日が好ましい。The dosage varies depending on the type and progress of the cancer, the patient's weight, preventive purposes, therapeutic purposes, etc. However, the oral dosage for therapeutic purposes, for example, is approximately 0.01-100 ml! /
Kg/l ~ 3 times/day. In particular, about 0.1 to 50
xy/ro/l to 3 times in 7 days is preferred.
この発明の抗腫瘍剤を経口投与剤として用いる場合は、
錠剤、カプセル剤（ソフトカプセル、マイクロカプセル
を含む）、液剤などの各種剤型にすることができる。一
方、非経口投与剤としては、注射剤、坐剤、経鼻剤など
がある。When using the antitumor agent of this invention as an orally administered agent,
It can be made into various dosage forms such as tablets, capsules (including soft capsules and microcapsules), and liquid preparations. On the other hand, parenteral preparations include injections, suppositories, and nasal preparations.
上記経口製剤中、たとえば錠剤を製造する際には、結合
剤（例、ヒドロキシプロピルセルロース、ヒドロキシプ
ロピルメチルセルロース、マクロゴールなど）、崩壊剤
（例、デンプン、カルボキシメチルセルロースカルシウ
ムなど）、賦形剤（例、乳糖、デンプンなど）、滑沢剤
（例、ステアリン酸マグネシウム、タルクなど）などを
適宜配合することができる。In the above oral preparations, for example, when manufacturing tablets, binders (e.g., hydroxypropylcellulose, hydroxypropylmethylcellulose, macrogol, etc.), disintegrants (e.g., starch, carboxymethylcellulose calcium, etc.), excipients (e.g. , lactose, starch, etc.), lubricants (eg, magnesium stearate, talc, etc.), etc. can be appropriately blended.
また、非経口製剤、たとえば注射剤を製造する際には、
等張化剤（例、ブドウ糖、Ｄ−ソルビトール、Ｄ−マン
ニトール、塩化ナトリウムなど）、防腐剤（例、ベンジ
ルアルコール、クロロブタノール、パラオキシ安息香酸
メチル、パラオキシ安息香酸プロピルなど）、緩衝剤（
例、リン酸緩衝液、酢酸ナトリウム緩衝液など）、溶解
剤（例、エチルアルコール、プロピレングリコール、ポ
リエチレングリコールなど）などを適宜配合することが
できる。In addition, when manufacturing parenteral preparations, such as injections,
Isotonic agents (e.g., glucose, D-sorbitol, D-mannitol, sodium chloride, etc.), preservatives (e.g., benzyl alcohol, chlorobutanol, methyl parahydroxybenzoate, propyl parahydroxybenzoate, etc.), buffers (
For example, a phosphate buffer, a sodium acetate buffer, etc.), a solubilizer (for example, ethyl alcohol, propylene glycol, polyethylene glycol, etc.), etc. can be appropriately blended.
その他の製剤は、当該分野の公知の技術を応用して作る
ことができる。Other formulations can be made by applying techniques known in the art.
この発明の抗腫瘍剤は哺乳動物（例、マウス、ラット、
ネコ、イヌ、牛、馬、羊、山羊、家兎、ヒト）の腫瘍、
ことに膀胱ガンの治療、再発防止または予防に有用であ
り、例えば腫瘍を保持する哺乳動物の延命に著効を奏す
る。膀胱ガン以外の対象疾患としては各種白血病、悪性
リンパ腫、骨肉腫、悪性黒色腫、悪性絨毛上皮、筋肉腫
、卵巣癌、子宮癌、前立腺癌、膵癌、肝癌、胃ならびに
腸などの消化器癌、肺癌、食道癌、顆頭部ｉｉｉ、脳腫
瘍などが挙げられる。The antitumor agent of this invention is applicable to mammals (e.g., mice, rats,
tumors in cats, dogs, cows, horses, sheep, goats, rabbits, and humans;
It is particularly useful for treating, preventing recurrence, or preventing bladder cancer, and is particularly effective in prolonging the life of mammals harboring tumors. Targeted diseases other than bladder cancer include various types of leukemia, malignant lymphoma, osteosarcoma, malignant melanoma, malignant villous epithelium, sarcoma, ovarian cancer, uterine cancer, prostate cancer, pancreatic cancer, liver cancer, gastrointestinal cancer such as stomach and intestine cancer, Examples include lung cancer, esophageal cancer, condylar head III, and brain tumor.
（ニ）実施例
次にこの発明の化合物（Ｉ）の代表例としてＲがｎ−オ
クタデシルである化合物（２−０−オクタデシルアスコ
ルビン酸（ＣＶ−３６１１））のこの発明者らの報告し
た前記文献の方法による抗腫瘍作用を示す。(d) Examples Next, as a representative example of the compound (I) of the present invention, the above-mentioned literature reported by the present inventors describes a compound in which R is n-octadecyl (2-0-octadecyl ascorbic acid (CV-3611)). It shows antitumor effect by the method of
実施例１
生後６週齢のウィスター系雄性ラットに、発癌剤である
Ｎ−ブチル−Ｎ−（４−ヒドロキシブチル）ニトロサミ
ン（ＢＨＢＮ）を０．０１％含む溶液を飲料水として１
週間自由摂取させ、その後、３週間、発癌プロモーター
であるサッカリンナトリウム（５％）もしくはＤＬ−）
リプトファン（２％）を含む粉末飼料（ＣＥ−２、日本
タレア製）を自由摂取させた。Example 1 A solution containing 0.01% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN), a carcinogenic agent, was given to 6-week-old Wistar male rats in their drinking water for 1 hour.
The carcinogenic promoter saccharin sodium (5%) or DL-) was given ad libitum for a week, and then for 3 weeks.
Powdered feed (CE-2, manufactured by Nippon Talea) containing liptophan (2%) was freely ingested.
被検化合物であるｃｖ−ａａｔｔは、サッカリンナトリ
ウムもしくはＤＬ−）リプトファンを含む飼料に０．０
０２％、０．００６％もしくは０．（Ｉ２％混合した。The test compound, cv-aatt, was added to feed containing saccharin sodium or DL-)liptophan at 0.0
02%, 0.006% or 0.02%. (2% I was mixed.
実験開始後４週目に動物を層殺し、膀胱を摘出し、膀胱
上皮細胞のコンカナバリンＡ （Ｃｏｎｃａｎａｖａｌ
ｉｎ Ａ ： Ｃｏｎ Ａ）に対する凝集能を測定した
。実験の全経過において、飼料採取量、動物の体重なら
びに外見所見に変化は見られなかった。Four weeks after the start of the experiment, the animals were sacrificed, the bladder was removed, and the bladder epithelial cells were treated with concanavalin A (Concanavalin A).
in A: The agglutination ability for Con A) was measured. During the entire course of the experiment, no changes were observed in feed intake, animal body weight, or physical appearance.
剥離した膀胱上皮細胞は５１ＭのＥＤＴＡ （エチレン
ジアミン四酢駿）を含む０．１５Ｍの食塩水で処理して
浮遊細胞を調製し、Ｃｏｎ Ａを４００ｕ９／ ｚ（ｌ
含むリン酸緩衝液（Ｉ３５ａＭ ＮａＣ１，２，７ｍＭ
ｌｌ：ｃｌ、 ８．１ｓＭ Ｎａｔｌ（ＰＯ，，１，
４６ｓ＋Ｍ Ｋ１１ｔＰ０４、ＰＨ７，４］、：浮遊（
５Ｘ １０”個／ｍｅ）させ、３０分後に細胞の凝集の
有無を顕微鏡下で観察した。なお、細胞数の測定は３１
以上の細胞が凝集しているものを凝集塊として計測し、
単細胞ならびに凝集塊の総数２００個あたりの凝集塊数
をもって表わした。The detached bladder epithelial cells were treated with 0.15M saline containing 51M EDTA (ethylenediaminetetraacetic acid) to prepare floating cells, and Con A was added to 400u9/z (l
Phosphate buffer containing (I35aM NaCl, 2, 7mM
ll:cl, 8.1sM Natl(PO,,1,
46s+M K11tP04, PH7,4], :Floating (
After 30 minutes, the presence or absence of cell aggregation was observed under a microscope.
The aggregates of the above cells are measured as aggregates,
It was expressed as the number of aggregates per 200 total number of single cells and aggregates.
（以下余白）
表
実験群
膀胱上皮細胞
０．０１ｎＨＢＮ ５％ ＋ｔ’ｈす／
００２％０．０１＄ＢＨＢＮ ５％ ｈ＊す／
０００６％６±０
７±０
０．０１＄ＢＨＢＮ ２％ ）リプドア７７
０．０２＄０、Ｏ１％ＢＩＩＢｊｌ ２％ ）リ
ブドアＴ７ ０．００６＄４±１
５±２
表■こ示すごとく、ＣＶ−３６１１を０．０２％、０．
００６％もしくは０．００２％添加した場合には、サッ
カリンもしくはＤＬ−トリプトファン添加による膀胱上
皮細胞のＣｏｎ Ａに対する凝集能の上昇が抑制された
。(Margin below) Table Experimental group Bladder epithelial cells 0.01nHBN 5% +t'hsu/
002%0.01$BHBN 5% h*su/
0006%6±0 7±0 0.01$BHBN 2%) Lipdore 77
0.02$0, O1%BIIBjl 2%) Ribbed Door T7 0.006$4±1 5±2 Table ■As shown, CV-3611 was added at 0.02%, 0.
When 0.006% or 0.002% was added, the increase in the aggregation ability of bladder epithelial cells to Con A due to the addition of saccharin or DL-tryptophan was suppressed.
実施例２
生後６週齢のウィスター系雄性ラットに、発癌剤ＢＨＢ
Ｎを０．０１％含む溶液を飲料水として４週間自由摂取
させた。Example 2 Carcinogenic agent BHB was administered to 6-week-old Wistar male rats.
A solution containing 0.01% N was freely ingested as drinking water for 4 weeks.
実験開始約１週間後よりＣＶ−３６１１を実施例１と同
様、０．０２％、０．００６％もしくは０．００２％を
含む粉末飼料を３週間自由摂取させ、実験開始４週間口
に実施例ｉと同様膀胱上皮細胞のＣｏｎ Ａに対する凝
集能を測定した。Approximately one week after the start of the experiment, powdered feed containing 0.02%, 0.006% or 0.002% of CV-3611 was given ad libitum for 3 weeks in the same manner as in Example 1. The aggregation ability of bladder epithelial cells to Con A was measured in the same manner as in i.
表２に示すごとく、ＣＶ−３６１１添加飼料を与えると
膀胱上皮細胞のＣｏｎ Ａに対する凝集能の上昇は抑制
された。As shown in Table 2, feeding the feed supplemented with CV-3611 suppressed the increase in the aggregation ability of bladder epithelial cells to Con A.
全経過を通じて、飲料摂取量ならびに体重の減少もしく
は外見所見の変化は見られなかった。No decrease in drink intake, body weight, or change in physical appearance was observed during the entire course.
表２
０．０１＄ＢＨＢＮ Ｏ，０２％ ２±１０
．０１＄ＢＨＢＮ ０．００６＄ ２±１
実施例３（肝腫瘍の自然発生の抑制）
生後７週令の雄のＣ３Ｈ／ Ｈｅ Ｎ Ｃｒ ｊマウス
を用い、対照群には基礎飼料（ＣＥ−２、日本タレア製
）を自由摂取させ、実験群には基礎飼料に被検化合物で
あるＣＶ−３６１１を０．１％混合して与え、１４〜１
６力月間飼育し、生存しｆニマウスについて剖検を行っ
１こ。実験の全過程において、飼料摂取量、動物の体重
並びに外見所見に変化は見られなかった。Table 2 0.01$BHBN O,02% 2±10
．． 01$BHBN 0.006$ 2±1
Example 3 (Suppression of Spontaneous Occurrence of Liver Tumors) Seven-week-old male C3H/He N Cr j mice were used, and the control group was given free access to basal feed (CE-2, Nippon Talea). The group was given basal feed mixed with 0.1% of the test compound CV-3611, and
After 6 months of breeding, one surviving mouse was autopsied. During the entire course of the experiment, no changes were observed in feed intake, animal body weight, or physical appearance.
剖検時に肝臓を肉眼的に観察し、発生しｆ二腫瘍の個数
を測定するとともに、常法に従って組織学的検索を行っ
た。At the time of autopsy, the liver was visually observed, the number of developed f2 tumors was measured, and a histological search was performed according to a conventional method.
表３に示すごと（、ＣＶ−３６１１をＯ１％添加した場
合には自然発生ｌ！ｉ瘍の個数には有意な差はなかった
が、肝細胞癌の発生（全腫瘍に対する比率：対照群３９
％、実験群９％）が顕著に抑制された。As shown in Table 3, there was no significant difference in the number of naturally occurring l!i tumors when CV-3611 was added at 1% O, but the incidence of hepatocellular carcinoma (ratio to total tumors: 39 in the control group).
%, experimental group 9%) was significantly suppressed.
（以下余白）
表３
実施例４（肺腫瘍の自然発生の抑制）
生後６週令の雄のＡ／ＴＮＣｒｊマウスを用い、対照群
には基礎飼料（ＣＥ−２、日本タレア製）を自由摂取さ
せ、実験群には基礎飼料に被検化合物であるＣＶ−３６
１１を０．１％混合して与え、１４力月間飼育後剖検を
行っＬ０実験の全過程において、飼料摂取量、動物の体
重並びに外見所見に変化は見られなかった。(Margins below) Table 3 Example 4 (Suppression of spontaneous lung tumor development) Six-week-old male A/TNCrj mice were used, and the control group was given free access to basal feed (CE-2, Nippon Talea). The experimental group received the test compound CV-36 in the basal diet.
No. 11 was fed in a 0.1% mixture, and necropsy was performed after 14 months of rearing. No changes were observed in feed intake, animal weight, or external appearance during the entire L0 experiment.
剖検時に肺臓を肉眼的に観察し、発生した腫瘍の個数を
測定するとともに、常法にしたがって組織学的検索を行
った。At the time of autopsy, the lungs were visually observed, the number of tumors that had developed was measured, and a histological search was performed according to a conventional method.
表４に示すごとく、ｃｖ−ｓｅｚを０．１％添加した場
合には自然発生踵の個数が７０％に減少し、また、特に
腺癌の発生（対照群１．０７７マウス、
実験群０．６２／マウス）が明瞭に抑制された。As shown in Table 4, when 0.1% cv-sez was added, the number of naturally occurring heels decreased to 70%, and especially the occurrence of adenocarcinoma (1.077 mice in the control group, 0.07 mice in the experimental group). 62/mouse) was clearly suppressed.
即ち、 腫瘍の自然発生とその悪性化が抑 制された。That is, Spontaneous tumor development and malignant progression are suppressed. It was controlled.
（ホ）発明の効果
この発明に係る化合物（Ｉ）は抗ｍ瘍作用を有し、抗腫
瘍剤として有用である。(E) Effects of the Invention Compound (I) according to the present invention has antitumor activity and is useful as an antitumor agent.
Claims (1)
）で示される２−０−アルキルアスコルビン酸または医
薬的に受容な塩を有効成分として含有することからなる
抗腫瘍剤。 ２、Ｒがｎ−オクタデシル基である請求項１に記載の抗
腫瘍剤。 ３、膀胱癌又は肝癌の予防、再発防止もしくは治療に用
いられる請求項１に記載の抗腫瘍剤。[Claims] 1. 2-0-alkylascorbic acid represented by the formula (I) ▲Mathematical formula, chemical formula, table, etc.▼(I) (In the formula, R represents an alkyl group of C_3 to C_2_2) Or an antitumor agent containing a pharmaceutically acceptable salt as an active ingredient. 2. The antitumor agent according to claim 1, wherein R is an n-octadecyl group. 3. The antitumor agent according to claim 1, which is used for prevention, prevention of recurrence, or treatment of bladder cancer or liver cancer.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23786589 | 1989-09-12 | ||
| JP1-237865 | 1989-09-12 | ||
| JP2-158263 | 1990-06-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04128225A true JPH04128225A (en) | 1992-04-28 |
Family
ID=17021566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24037890A Pending JPH04128225A (en) | 1989-09-12 | 1990-09-10 | Antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04128225A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996030012A1 (en) * | 1995-03-24 | 1996-10-03 | Defeudis Francis V | Methods for treating conditions associated with excess nitric oxide |
| WO2008090717A1 (en) * | 2007-01-26 | 2008-07-31 | Shiseido Company, Ltd. | Adam inhibitor |
| JP2019006692A (en) * | 2017-06-22 | 2019-01-17 | 公立大学法人県立広島大学 | Antiallergic agent, mediator-isolation inhibitor, and oral medicine |
-
1990
- 1990-09-10 JP JP24037890A patent/JPH04128225A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996030012A1 (en) * | 1995-03-24 | 1996-10-03 | Defeudis Francis V | Methods for treating conditions associated with excess nitric oxide |
| WO2008090717A1 (en) * | 2007-01-26 | 2008-07-31 | Shiseido Company, Ltd. | Adam inhibitor |
| JP2008184387A (en) * | 2007-01-26 | 2008-08-14 | Shiseido Co Ltd | Adam inhibitor |
| EP2123272A4 (en) * | 2007-01-26 | 2010-04-21 | Shiseido Co Ltd | Adam inhibitor |
| JP2019006692A (en) * | 2017-06-22 | 2019-01-17 | 公立大学法人県立広島大学 | Antiallergic agent, mediator-isolation inhibitor, and oral medicine |
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