JPH0853351A - Enzyme-inhibiting agent, arterialization-inhibiting agent, and cancer metastasis-inhibiting agent - Google Patents
Enzyme-inhibiting agent, arterialization-inhibiting agent, and cancer metastasis-inhibiting agentInfo
- Publication number
- JPH0853351A JPH0853351A JP20932194A JP20932194A JPH0853351A JP H0853351 A JPH0853351 A JP H0853351A JP 20932194 A JP20932194 A JP 20932194A JP 20932194 A JP20932194 A JP 20932194A JP H0853351 A JPH0853351 A JP H0853351A
- Authority
- JP
- Japan
- Prior art keywords
- inhibiting agent
- derivative
- active ingredient
- inhibiting
- docosahexaenoic acid
- 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
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明は、ドコサヘキサエン酸お
よび/またはその誘導体を有効成分とすることを特徴と
する酵素阻害剤、血管新生抑制剤および癌転移抑制剤に
関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an enzyme inhibitor, an angiogenesis inhibitor and a cancer metastasis inhibitor characterized by containing docosahexaenoic acid and / or its derivative as an active ingredient.
【0002】[0002]
【従来の技術】わが国において、成人病による死亡者の
うち、癌を原因とする死亡者の割合は年々増加する傾向
にある。癌の治療法および転移メカニズムに関する研究
は近年急激な進歩を遂げているが、画期的な治療法は未
だ発見されておらず、化学療法剤を用いた治療でも十分
な効果は得られていない。癌による死亡のほとんどは転
移が原因であり、転移抑制が癌死亡者を減少させる良策
であると考えられる。従来、オボスタチン、マトリスタ
チン、アプロチニン等が癌転移抑制剤として知られてい
るが、その効果は未だ不十分なものであった。2. Description of the Related Art In Japan, the percentage of deaths due to cancer among adult deaths tends to increase year by year. Although research on cancer treatment and metastasis mechanism has made rapid progress in recent years, no epoch-making treatment has been discovered yet, and treatment with chemotherapeutic agents has not been sufficiently effective. . Most cancer deaths are due to metastasis, and suppression of metastasis is considered a good measure to reduce cancer deaths. Conventionally, ovostatin, matristatin, aprotinin and the like have been known as cancer metastasis inhibitors, but their effects have not been sufficient yet.
【0003】一方、ドコサヘキサエン酸(DHA)は脳
や網膜等の興奮性膜に多く含まれているn−3系の不飽
和脂肪酸であり、記憶、学習能の改善、視力低下抑制、
抗腫瘍作用、免疫抑制作用等の薬理作用があるとされて
いる。DHAを多く含む魚油にもマクロファージの活性
を抑制したり(Dustin L. B., et al., J. IMMUNOL,14
4,488-4897 (1990))、LTB4、LTC4の産生抑制(L
okesh B. R., et al.,Biochem Biophys Acta, 958,99-1
07, (1988))、TNFの産生を抑止しするという報告
(Endres S., et al., N. Eng. J. Med.,320,265-271,
(1989) )があり、臓器移植においてCyAと併用する
と免疫抑制効果が増強されるとの報告(Kelley V. E.,e
t al., Transplantation,48,98-102,(1989))がある。
しかしながら、酵素阻害作用あるいは血管新生抑制作
用、さらには癌転移抑制作用についての報告はない。On the other hand, docosahexaenoic acid (DHA) is an n-3 type unsaturated fatty acid contained in excitable membranes such as the brain and retina in a large amount, and improves memory and learning ability and suppresses deterioration of visual acuity.
It is said to have pharmacological actions such as antitumor action and immunosuppressive action. It also inhibits macrophage activity in fish oil containing a large amount of DHA (Dustin LB, et al., J. IMMUNOL, 14
4,488-4897 (1990)), LTB 4 and LTC 4 production inhibition (L
okesh BR, et al., Biochem Biophys Acta, 958,99-1
07, (1988)), which suppresses the production of TNF (Endres S., et al., N. Eng. J. Med., 320, 265-271,
(1989)) and reported that the immunosuppressive effect was enhanced when combined with CyA in organ transplantation (Kelley VE, e
al., Transplantation, 48, 98-102, (1989)).
However, there is no report on the enzyme inhibitory action, the angiogenesis inhibitory action, and further the cancer metastasis inhibitory action.
【0004】[0004]
【発明が解決しようとする課題】癌転移は多段階よりな
る非常に複雑な現象であり、癌細胞の原発巣からの離
脱、血管内への侵入、血管内皮細胞への接着、血管基底
膜の破壊、そして細胞外マトリックスへの浸潤、増殖と
いう過程をとる。これらの過程には種々の酵素が関与し
ており、それらの阻害物質が新しい癌転移抑制剤として
注目されている。また、癌細胞は、その特徴である異常
増殖を発現する上で必要な栄養および酵素の供給、ある
いは代謝老廃物の排泄を行うため、血管新生を誘導す
る。それ故、血管新生を阻害することにより癌細胞の増
殖を抑制し、癌の転移を抑制しうる。Cancer metastasis is a very complex phenomenon consisting of multiple stages. Cancer cells are detached from the primary lesion, invaded into blood vessels, adhered to vascular endothelial cells, and adhering to vascular basement membrane. The process involves destruction, invasion of extracellular matrix, and proliferation. Various enzymes are involved in these processes, and their inhibitors are attracting attention as new cancer metastasis inhibitors. Further, cancer cells induce angiogenesis because they supply nutrients and enzymes necessary for expressing the abnormal growth that is a characteristic of cancer cells, or excrete metabolic waste products. Therefore, by inhibiting angiogenesis, the growth of cancer cells can be suppressed and the metastasis of cancer can be suppressed.
【0005】[0005]
【課題を解決するための手段】本発明者等は、新たな癌
転移抑制剤を開発すべく鋭意研究した結果、ドコサヘキ
サエン酸および/またはその誘導体が、酵素を阻害し、
また、血管の新生を抑制することを見いだし、本発明を
完成するに至った。Means for Solving the Problems The inventors of the present invention have conducted extensive studies to develop a new cancer metastasis inhibitor, and as a result, docosahexaenoic acid and / or its derivative inhibits the enzyme,
In addition, they found that the formation of blood vessels was suppressed, and completed the present invention.
【0006】すなわち本発明は、ドコサヘキサエン酸お
よび/またはその誘導体を有効成分とする酵素阻害剤を
提供する。また本発明は、ドコサヘキサエン酸および/
またはその誘導体を有効成分とする血管新生抑制剤を提
供する。さらに本発明は、ドコサヘキサエン酸および/
またはその誘導体を有効成分とする癌転移抑制剤を提供
する。That is, the present invention provides an enzyme inhibitor containing docosahexaenoic acid and / or its derivative as an active ingredient. The present invention also relates to docosahexaenoic acid and / or
Alternatively, an angiogenesis inhibitor containing the derivative thereof as an active ingredient is provided. Furthermore, the present invention relates to docosahexaenoic acid and / or
Alternatively, a cancer metastasis inhibitor containing the derivative thereof as an active ingredient is provided.
【0007】本発明に用いるドコサヘキサエン酸および
その誘導体(以下、DHA類という)とは、遊離酸(す
なわちDHA)をはじめ、その塩(例えば、ナトリウム
塩、カリウム塩、カルシウム塩、アンモニウム塩)、エ
ステル(例えば、メチルエステル、エチルエステル、プ
ロピルエステル)、グリセリド(モノ−、ジ−、トリ
−)、リン脂質、コリン化合物、アスコルビン酸化合
物、アミノ酸化合物等を意味する。ドコサヘキサエン酸
は、イワシ、サバ、アジ、サケ、サンマなどの青背魚よ
り抽出した魚油、マグロやカツオなどの大型海産魚の眼
窩脂肪由来の魚油、微生物や海草由来の油脂、オキアミ
油、タラやイカ肝臓より抽出した海産物由来の油脂など
から、公知の方法にしたがって単離精製して得られる。Docosahexaenoic acid and its derivatives (hereinafter referred to as DHAs) used in the present invention include free acids (that is, DHA), their salts (for example, sodium salt, potassium salt, calcium salt, ammonium salt) and esters. (For example, methyl ester, ethyl ester, propyl ester), glyceride (mono-, di-, tri-), phospholipid, choline compound, ascorbic acid compound, amino acid compound and the like. Docosahexaenoic acid is fish oil extracted from blue-backed fish such as sardines, mackerel, horse mackerel, salmon, saury, fish oil derived from orbital fat of large marine fish such as tuna and bonito, oil and fat derived from microorganisms and seaweeds, krill oil, cod and squid. It can be obtained by isolation and purification from seafood-derived oils and fats extracted from the liver according to known methods.
【0008】DHAの毒性は弱く、例えばそのエチルエ
ステルをマウスに2000mg/kg経口投与しても毒
性の徴候は何ら見られなかった。The toxicity of DHA is weak, and no sign of toxicity was observed when the ethyl ester was orally administered to mice at 2000 mg / kg.
【0009】これらDHA類の投与量は、対象疾患の種
類、患者の年齢、性別、体重、症状、あるいは投与形態
により異なるが、一般には、成人一日あたり約0.1〜
5g、好ましくは1〜2.5gであり、1回あるいは数
回に分けて投与するのが適当である。The dose of these DHAs varies depending on the type of target disease, age, sex, body weight, symptom of patient, or administration form, but in general, about 0.1 to 0.1 per day for an adult.
It is 5 g, preferably 1 to 2.5 g, and it is suitable to administer the drug once or in several divided doses.
【0010】本発明の薬剤は治療のために経口的あるい
は非経口的に投与することができる。経口投与剤として
は散剤、顆粒剤、カプセル剤、錠剤などの固形製剤ある
いはシロップ剤、エリキシル剤などの液状製剤とするこ
とができる。また、非経口投与剤として注射剤とするこ
とができる。The drug of the present invention can be administered orally or parenterally for therapeutic purposes. As the orally-administered agent, solid preparations such as powder, granules, capsules and tablets, or liquid preparations such as syrups and elixirs can be used. Moreover, an injection can be prepared as a parenteral preparation.
【0011】これらの製剤は活性成分に薬理学的、製剤
学的に認容される製造助剤を加えることにより常法に従
って製造される。更に公知の技術により持続性製剤とす
ることも可能である。当該製造助剤を用いる場合は、D
HA類(遊離酸として)の配合量は通常は1〜90重量
%、好ましくは10〜80重量%である。These preparations are manufactured according to a conventional method by adding pharmacologically and pharmaceutically acceptable manufacturing aids to the active ingredient. Further, it is also possible to prepare a sustained-release preparation by a known technique. When using the manufacturing aid, D
The content of HAs (as free acid) is usually 1 to 90% by weight, preferably 10 to 80% by weight.
【0012】上記製造助剤としては、内服用製剤(経口
剤)、注射用製材(注射剤)、粘膜投与剤(バッカル、
トロ−チ、坐剤等)、外用剤(軟膏、貼付剤等)などの
投与経路に応じた適当な製剤用成分から使用される。[0012] The above-mentioned production aids include oral preparations (oral preparations), injection lumber (injection preparations), mucosal administration preparations (buccal,
Troches, suppositories, etc.), external preparations (ointments, patches, etc.), and other suitable ingredients for formulation depending on the route of administration.
【0013】例えば、経口剤および粘膜投与剤にあって
は、賦形剤(例:澱粉、乳糖、結晶セルロース、乳糖カ
ルシウム、メタケイ酸アルミン酸マグネシウム、無水ケ
イ酸)、崩壊剤(例:カルボキシメチルセルロ−ス、カ
ルボキシメチルセルロースカルシウム)、滑沢剤(例:
ステアリン酸マグネシム、タルク)、コ−テング剤
(例:ヒドロキシエチルセルロ−ス、白糖、ヒドロキシ
プロピルセルロース、ポリビニルピロリドン、トウモロ
コシ蛋白)、矯味剤などの製剤用成分が使用される。For example, in the case of oral agents and mucosal agents, excipients (eg, starch, lactose, crystalline cellulose, calcium lactose, magnesium aluminometasilicate, anhydrous silicic acid), disintegrating agents (eg, carboxymethyl) Cellulose, carboxymethylcellulose calcium), lubricant (eg:
Pharmaceutical ingredients such as magnesium stearate, talc), co-tenting agents (eg hydroxyethyl cellulose, sucrose, hydroxypropyl cellulose, polyvinylpyrrolidone, corn protein), flavoring agents and the like are used.
【0014】顆粒剤を製造するには湿式又は乾式造粒
し、錠剤を製造するにはこれらの散剤及び顆粒剤をその
ままあるいはステアリン酸マグネシウム、タルクなどの
滑沢剤を加えて打錠すればよい。これらの顆粒又は錠剤
はヒドロキシプロピルメチルセルロースフタレート、メ
タアクリル酸、メタアクリル酸メチルコポリマーなどの
腸溶性基剤で被覆して腸溶性製剤、あるいはエチルセル
ロース、カルナウバロウ、硬化油などで被覆して持続性
製剤とすることもできる。また、カプセル剤を製造する
には散剤又は顆粒剤を硬カプセルに充填するか、活性成
分をグリセリン、ポリエチレングリコール、ゴマ油、オ
リーブ油などに溶解したのちゼラチン膜で被覆し軟カプ
セル剤とすることができる。カプセル剤の場合には、内
容物として、DHA類が100重量%であってもよい。To produce granules, wet or dry granulation may be carried out, and to produce tablets, these powders and granules may be tableted as they are or by adding a lubricant such as magnesium stearate or talc. . These granules or tablets are coated with an enteric base such as hydroxypropylmethyl cellulose phthalate, methacrylic acid, and methyl methacrylate copolymer to form an enteric preparation, or coated with ethyl cellulose, carnauba wax, hardened oil, etc. to form a sustained-release preparation. You can also do it. Further, in order to produce a capsule, a powder or granules can be filled in a hard capsule, or the active ingredient can be dissolved in glycerin, polyethylene glycol, sesame oil, olive oil, etc. and then coated with a gelatin film to give a soft capsule. . In the case of capsules, the content may be 100% by weight of DHAs.
【0015】経口投与用の液状製剤を製造するには活性
成分と白糖、ソルビトール、グリセリンなどの甘味剤と
を水に溶解して透明なシロップ剤、更に精油、エタノー
ルなどを加えてエリキシル剤とするか、アラビアゴム、
トラガント、ポリソルベート80、カルボキシメチルセ
ルロースナトリウムなどを加えて乳剤又は懸濁剤として
もよい。これらの液状製剤には所望により矯味剤、着色
剤、保存剤などを加えてもよい。To prepare a liquid preparation for oral administration, an active ingredient and a sweetener such as sucrose, sorbitol and glycerin are dissolved in water to prepare a transparent syrup, and essential oil, ethanol and the like are added to form an elixir. Or gum arabic,
An emulsion or suspension may be prepared by adding tragacanth, polysorbate 80, sodium carboxymethyl cellulose and the like. If desired, flavoring agents, coloring agents, preservatives and the like may be added to these liquid preparations.
【0016】また注射剤にあっては、水性注射剤を構成
し得る溶解剤ないし溶解補助剤(例:注射用蒸留水、生
理食塩水、プロピレングリコ−ル)、懸濁化剤(例:ポ
リソルベ−ト80などの界面活性剤)、pH調整剤
(例:有機酸またはその金属塩)、安定剤などの製剤用
成分が使用される。注射剤を製造するには活性成分を必
要に応じ塩酸、水酸化ナトリウム、乳剤、乳酸ナトリウ
ム、リン酸一水素ナトリウム、リン酸二水素ナトリウム
などのpH調整剤、塩化ナトリウム、ブドウ糖などの等
張化剤とともに注射用蒸留水に溶解し、無菌濾過してア
ンプルに充填するか、更にマンニトール、デキストリ
ン、シクロデキストリン、ゼラチンなどを加えて真空下
凍結乾燥し、用時溶解型の注射剤としてもよいし、活性
成分にレシチン、ポリソルベート80、ポリオキシエチ
レン硬化ヒマシ油などを加えて水中で乳化せしめ注射用
乳剤とすることもできる。In the case of injectable preparations, solubilizers or solubilizing agents (eg, distilled water for injection, physiological saline, propylene glycol), suspending agents (eg, polysorbate) capable of forming an aqueous injectable preparation. -Pharmaceutical ingredients such as surfactants such as 80), pH adjusters (eg, organic acids or metal salts thereof), stabilizers, etc. are used. In order to produce an injection, the active ingredient is adjusted as necessary with hydrochloric acid, sodium hydroxide, emulsion, sodium lactate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, etc. pH adjusting agents, sodium chloride, glucose, etc. It may be dissolved in distilled water for injection with the agent, aseptically filtered and filled in an ampoule, or mannitol, dextrin, cyclodextrin, gelatin, etc. may be added and freeze-dried under vacuum to give a solution-injectable injection at the time of use. Alternatively, lecithin, polysorbate 80, polyoxyethylene hydrogenated castor oil, etc. may be added to the active ingredient and emulsified in water to give an emulsion for injection.
【0017】その他、上記構成を有する本発明の薬剤
は、公知の製造法、例えば日本薬局方第10版製剤総則
記載の方法ないし適当な改良を加えた方法によっても製
造することができる。In addition, the drug of the present invention having the above-mentioned constitution can be manufactured by a known manufacturing method, for example, the method described in the Japanese Pharmacopoeia 10th Edition General Rules for Preparation or a method with appropriate modification.
【0018】以下、本発明を実施例により詳細に説明す
る。The present invention will be described in detail below with reference to examples.
【0019】[0019]
実施例1. 酵素阻害活性試験 多価不飽和脂肪酸[(DHA,エイコサペンタエン酸
(EPA),エイコサテトラエン酸(ETA)の各々エ
チルエステル]は、投与前2週間F1−フィッシュミー
ルで飼育したSPF−Balb/c AnNCrj マウス(6周
令、雄)に、50mg/kg/日/1回を5%アラビア
ゴム水溶液に溶かし、ゾンデで10日間経口投与した。
最終投与24時間後に麻酔下に屠殺し、脾臓を摘出し
た。摘出した脾臓は冷PBS(リン酸緩衝液、phosphat
e buffered saline)でヒストコロン(日音医理科器械
製作所、東京)を用いホモジナイズした。3,000g
で20分間遠心分離したのち、その上清の酵素活性を測
定した。Example 1. Enzyme Inhibitory Activity Test Polyunsaturated fatty acids [(Ethyl ester of each of DHA, eicosapentaenoic acid (EPA), eicosatetraenoic acid (ETA)] were SPF-Balb / fed in F1-fish meal for 2 weeks before administration. c AnNCrj mouse (6 weeks old, male) was dissolved in a 5% aqueous solution of gum arabic at a dose of 50 mg / kg / day / once and orally administered by a sonde for 10 days.
24 hours after the final administration, the animals were sacrificed under anesthesia and the spleen was extracted. The extracted spleen is cold PBS (phosphate buffer, phosphat
e buffered saline) was used for homogenization using a histocol (Nippon Medical and Scientific Instruments, Tokyo). 3,000g
After centrifuging at 20 minutes, the enzyme activity of the supernatant was measured.
【0020】[0020]
【表1】 注:*P<0.05,**P<0.01,*** P<0.001[Table 1] Note: * P <0.05, ** P <0.01, *** P <0.001
【0021】このように、DHAはEPAに比べてより
強い酵素阻害活性を示した。As described above, DHA showed a stronger enzyme inhibitory activity than EPA.
【0022】実施例2. 血管新生抑制活性 コリオアラントイック メンブラン(Chorioallantoic
membrane CAM)法 受精3日目の鶏卵の上部と側面を70%エタノールで消
毒した。次にキリで上部と側面に各1ヶ所づつ穴を開
け、側面の穴より約2ml卵白を吸引除去し、上部の穴よ
りスポイトを用いて空気を少量抜いた。側面の穴はオプ
サイト(Smith &Nephew Medical Limited,USA)を貼っ
て塞ぎ、続いてドラフト内で上部の殻を剥ぎ、テフロン
製キャップをして37℃で1日培養した。その後CAM
上にシリコン製キャップを置き、そのリング内に1%メ
チルセルロース含有生理食塩水に懸濁した試料10μl
を注入した。各群6個づつの卵を使用した。さらに、2
日間、37℃で培養した後、殻を大きく開け、CAM内
にイントラリポスを注入し、阻害効果の判定及び写真撮
影を行った。Example 2. Anti-angiogenic activity Chorioallantoic membrane (Chorioallantoic)
Membrane CAM) Method On the 3rd day of fertilization, the top and sides of the egg were sterilized with 70% ethanol. Next, a hole was made in the upper and side surfaces with a hole, about 2 ml of egg white was suctioned and removed from the side hole, and a small amount of air was removed from the upper hole using a dropper. Optics (Smith & Nephew Medical Limited, USA) were pasted on the side holes to close the holes, and then the upper shell was peeled off in a draft, and a cap made of Teflon was put on, and the plate was incubated at 37 ° C for 1 day. Then CAM
Place a silicon cap on top, and in the ring 10 μl of sample suspended in physiological saline containing 1% methylcellulose
Was injected. Six eggs were used in each group. Furthermore, 2
After culturing at 37 ° C. for one day, the shell was opened wide, intralipos was injected into the CAM, and the inhibitory effect was determined and a photograph was taken.
【0023】[0023]
【表2】表2. 多価不飽和脂肪酸の血管新生抑制試験 ────────────────────── 試料 投与量 阻害率(%)2) 効果3) ────────────────────── DHA 0.2mg/CAM 66.7 2.5 EPA 0.2mg/CAM 50.0 1.5 ETA 0.2mg/CAM 33.3 1.0 ──────────────────────[Table 2] Table 2. Angiogenesis inhibition test of polyunsaturated fatty acids ────────────────────── Sample dose inhibition rate (%) 2) Effect 3) ───── ───────────────── DHA 0.2mg / CAM 66.7 2.5 EPA 0.2mg / CAM 50.0 1.5 ETA 0.2mg / CAM 33.3 1.0 ──────────────────────
【0024】1)各々エチルエステル体を投与 2)血管新生が阻害された卵の全体に対する百分率を表
す。 3)血管新生の阻害の強さを−,±,+,++,+++
の5段階で評価し、各々に0,1,2,3,4の得点を
与え、その積算値をn数で除した値を表す。1) Administration of each ethyl ester compound 2) Representation of the percentage of eggs in which angiogenesis is inhibited, based on the whole eggs. 3) The strength of inhibition of angiogenesis is-, ±, +, ++, +++
It is evaluated on the basis of 5 grades, a score of 0, 1, 2, 3, 4 is given to each, and the integrated value is divided by n.
【0025】この結果、DHAがEPAやETAに比べ
て有意に血管の新生を抑制することが判明した。As a result, it was revealed that DHA significantly suppressed the neovascularization as compared with EPA and ETA.
【0026】[0026]
【発明の効果】ドコサヘキサエン酸およびその誘導体は
酵素を阻害し、血管新生を抑制する。従って、ドコサヘ
キサエン酸および/またはその誘導体は、酵素阻害剤、
血管新生抑制剤、ひいては癌転移抑制剤として有効に用
いることができる。EFFECTS OF THE INVENTION Docosahexaenoic acid and its derivatives inhibit enzymes and suppress angiogenesis. Therefore, docosahexaenoic acid and / or its derivatives are
It can be effectively used as an angiogenesis inhibitor, and further as a cancer metastasis inhibitor.
Claims (3)
誘導体を有効成分とする酵素阻害剤。1. An enzyme inhibitor comprising docosahexaenoic acid and / or its derivative as an active ingredient.
誘導体を有効成分とする血管新生抑制剤。2. An angiogenesis inhibitor containing docosahexaenoic acid and / or its derivative as an active ingredient.
誘導体を有効成分とする癌転移抑制剤。3. A cancer metastasis inhibitor containing docosahexaenoic acid and / or its derivative as an active ingredient.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP20932194A JPH0853351A (en) | 1994-08-11 | 1994-08-11 | Enzyme-inhibiting agent, arterialization-inhibiting agent, and cancer metastasis-inhibiting agent |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP20932194A JPH0853351A (en) | 1994-08-11 | 1994-08-11 | Enzyme-inhibiting agent, arterialization-inhibiting agent, and cancer metastasis-inhibiting agent |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH0853351A true JPH0853351A (en) | 1996-02-27 |
Family
ID=16571020
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP20932194A Pending JPH0853351A (en) | 1994-08-11 | 1994-08-11 | Enzyme-inhibiting agent, arterialization-inhibiting agent, and cancer metastasis-inhibiting agent |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH0853351A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003508484A (en) * | 1999-09-10 | 2003-03-04 | モンサント テクノロジー エルエルシー | Use of alpha-linolenic acid metabolite for the treatment or prevention of cancer |
WO2005032536A1 (en) * | 2003-10-03 | 2005-04-14 | Ono Pharmaceutical Co., Ltd. | Drug containing (2r)-2-propyloctanoic acid as the active ingredient |
WO2005032538A1 (en) * | 2003-10-03 | 2005-04-14 | Ono Pharmaceutical Co., Ltd. | Infusion preparation containing (2r)-2-propyloctanoic acid as the active ingredient |
JP2007511531A (en) * | 2003-11-13 | 2007-05-10 | カリフォルニア パシフィック メディカル センター | Anti-PECAM treatment for metastasis suppression |
-
1994
- 1994-08-11 JP JP20932194A patent/JPH0853351A/en active Pending
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003508484A (en) * | 1999-09-10 | 2003-03-04 | モンサント テクノロジー エルエルシー | Use of alpha-linolenic acid metabolite for the treatment or prevention of cancer |
WO2005032536A1 (en) * | 2003-10-03 | 2005-04-14 | Ono Pharmaceutical Co., Ltd. | Drug containing (2r)-2-propyloctanoic acid as the active ingredient |
WO2005032538A1 (en) * | 2003-10-03 | 2005-04-14 | Ono Pharmaceutical Co., Ltd. | Infusion preparation containing (2r)-2-propyloctanoic acid as the active ingredient |
JPWO2005032538A1 (en) * | 2003-10-03 | 2006-12-14 | 小野薬品工業株式会社 | Infusion formulation containing (2R) -2-propyloctanoic acid as an active ingredient |
JPWO2005032536A1 (en) * | 2003-10-03 | 2006-12-14 | 小野薬品工業株式会社 | Drugs containing (2R) -2-propyloctanoic acid as an active ingredient |
JP4715516B2 (en) * | 2003-10-03 | 2011-07-06 | 小野薬品工業株式会社 | Infusion formulation containing (2R) -2-propyloctanoic acid as an active ingredient |
JP4715515B2 (en) * | 2003-10-03 | 2011-07-06 | 小野薬品工業株式会社 | Drugs containing (2R) -2-propyloctanoic acid as an active ingredient |
US8053599B2 (en) | 2003-10-03 | 2011-11-08 | Ono Pharmaceutical Co., Ltd. | Drug containing (2R)-2-propyloctanoic acid as the active ingredient |
JP2007511531A (en) * | 2003-11-13 | 2007-05-10 | カリフォルニア パシフィック メディカル センター | Anti-PECAM treatment for metastasis suppression |
JP4897490B2 (en) * | 2003-11-13 | 2012-03-14 | サッター・ウエスト・ベイ・ホスピタルズ | Anti-PECAM treatment for metastasis suppression |
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