JPS63267718A - Antitumor agent - Google Patents
Antitumor agentInfo
- Publication number
- JPS63267718A JPS63267718A JP62100440A JP10044087A JPS63267718A JP S63267718 A JPS63267718 A JP S63267718A JP 62100440 A JP62100440 A JP 62100440A JP 10044087 A JP10044087 A JP 10044087A JP S63267718 A JPS63267718 A JP S63267718A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- acid
- lactone
- buteonic
- acetamido
- 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 11
- 239000004480 active ingredient Substances 0.000 claims abstract description 8
- 206010028980 Neoplasm Diseases 0.000 abstract description 9
- 201000011510 cancer Diseases 0.000 abstract description 9
- 230000004069 differentiation Effects 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 8
- 230000001939 inductive effect Effects 0.000 abstract description 6
- 230000000259 anti-tumor effect Effects 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 241000283690 Bos taurus Species 0.000 abstract description 2
- 230000017074 necrotic cell death Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 210000000214 mouth Anatomy 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- -1 multidose Chemical compound 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 238000010998 test method Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 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 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 241000978776 Senegalia senegal Species 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000007093 Leukemia L1210 Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 102000054896 human PML Human genes 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、抗腫瘍剤に関する。更に詳しくは、癌増殖阻
害作用、癌分化誘導作用を持つ４−アセタミド−４−ヒ
ドロキシ−２−ブテオニックアシッド−γ−ラクトンを
含有する抗腫瘍剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an antitumor agent. More specifically, the present invention relates to an antitumor agent containing 4-acetamido-4-hydroxy-2-buteonic acid-γ-lactone, which has a cancer growth inhibiting effect and a cancer differentiation inducing effect.
［従来の技術］
４−アセタミド−４−ヒドロキシ−２−ブチオニツタア
シッド−７−ラクトンは、既知物質であり、牛の壊厄の
起因物質として知られている。[Prior Art] 4-acetamido-4-hydroxy-2-butionittaic acid-7-lactone is a known substance and is known to be a causative agent of necrosis in cattle.
文献上は、ジャーナル 才ブ ケミカルソサイティ−（
Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｃａｌ ５ｏｃｉｅ
ｔｙ）（Ｃ）。In the literature, the journal Saibu Chemical Society (
Journal of Chemical 5ocie
ty) (C).
第３４６頁、１９６７年、ジャーナル 才ブ アグリ力
ルチャラル フードケミストリー（Ｊｏｌｎｒｎａｌ
ｏｆＡｇｒｉｃｕｌｔｕｒａｌ Ｆｏｏｄ Ｃｈｅｍ
ｉｓｔｒｙ）第１７巻、第７３４頁。No. 346, 1967, Journal of Agricultural Food Chemistry
ofAgricultural Food Chem
istry) Volume 17, Page 734.
１９７０年に記載がある。It was described in 1970.
しかし、この４−アセタミド−４−ヒドロキシ−２−ブ
テオニックアシッド−γ−ラクトンの医薬用途に関する
報告、例えば、抗腫瘍作用、癌分化誘導作用についての
報告は知られていない。However, there are no known reports regarding the medical use of this 4-acetamido-4-hydroxy-2-buteonic acid-γ-lactone, such as antitumor effects and cancer differentiation-inducing effects.
［発明が解決しようとする問題点］
悪性ＩＩ！！ｆＭは、その性質が千差万別であるため、
新規な抗腫瘍剤の開発が望まれている。[Problems to be solved by the invention] Malignancy II! ! Since the properties of fM vary widely,
The development of new antitumor agents is desired.
［問題点を解決するための手段］
本発明者等は、上記問題点に鑑み、カビ代謝産物中に抗
腫瘍物質、癌分化誘導作用物質を求め鋭意検討した結果
、４−アセタミド−４−ヒドロキシー２−ブテオニック
アシッド−γ−ラクトンが、癌増殖阻害作用、癌分化誘
導作用を有することを見出し、この知見に基づき本発明
を完成するに至った。[Means for Solving the Problems] In view of the above-mentioned problems, the inventors of the present invention have searched for anti-tumor substances and cancer differentiation-inducing substances in fungal metabolites, and as a result of intensive studies, they have found that 4-acetamido-4-hydroxy It was discovered that 2-buteonic acid-γ-lactone has a cancer growth inhibiting effect and a cancer differentiation inducing effect, and based on this knowledge, the present invention was completed.
本発明の抗腫瘍剤の有効成分である４−アセタミド−４
−ヒドロキシ−２−ブテオニックアシッド−γ−ラクト
ンは既知物質であって、例えば、合成的に、ジャーナル
才プ ケミ力ルソサイテイ−（Ｊｏｕｒｎａｌ ｏｆ
Ｃｈｅｍｉｃａｌ ５ｏｃｉｅｔｙ）（Ｃ）。4-acetamide-4, which is the active ingredient of the antitumor agent of the present invention
-Hydroxy-2-buteonic acid-gamma-lactone is a known substance, for example, it can be synthesized synthetically in the Journal of Chemistry.
Chemical 5ociety) (C).
第３４６頁、１９６７年、に記載の方法によって得るこ
とができ、ジャーナル 才ブ アグリカルチ〜ラルフー
ドケミストリー（Ｊｏｕｒｎａｌ ｏｆ Ａｇｒｉｃｕ
ｌｔｕｒａｌＦｏｏｄ Ｃｈｅｍｉｓｔｒｙ ）第１７
巻、第７３４頁、 １９７０年、に記載の方法で培養液
から種々の精製単離手段によっても得られる。346, 1967, by the method described in Journal of Agricultural Food Chemistry.
ulturalFood Chemistry) No. 17
Vol., p. 734, 1970, it can also be obtained from the culture medium by various purification and isolation methods.
本発明の抗ｒｎ瘍剤の有効成分である４−アセタミド−
４−ヒドロキシ−２−ブテオニックアシッド−γ−ラク
トンの投与量は、患者の年齢、性別、症状、所望の治療
効果を考慮して、決定きれるものであるが、通常成人日
用（ｉｏ、 ０５〜１００■（有効成分量）を基準とし
て定めることが好ましい。4-acetamide, which is an active ingredient of the anti-inflammatory drug of the present invention
The dosage of 4-hydroxy-2-buteonic acid-γ-lactone can be determined by taking into consideration the patient's age, sex, symptoms, and desired therapeutic effect, but it is usually administered in an adult daily dose (io, It is preferable to set the amount on the basis of 0.05 to 100 μm (amount of active ingredient).
投与方法としては、注射、経口、直腸などの各投与法が
可能である。Possible administration methods include injection, oral administration, and rectal administration.
製剤中の含量は製剤形態により広範囲に変えることが可
能であり、一般には、０．０１〜ｔｏｏｆｆｉ−１２好
＊ ｔ、 ＜ ハ、０．１〜７０！！ｌｆｆ１％テある
。The content in the formulation can vary widely depending on the formulation, and generally ranges from 0.01 to tooffi-12, <ha, 0.1 to 70! ! There is lff1%te.
製剤化に際しては、注射剤、粉末剤、顆粒剤、錠剤、量
刑などの剤形がとり得る。またその他に本発明の抗腫瘍
剤の有効成分である４−アセタミド−４−ヒドロキシ−
２−ブテオニックアシッド−γ−ラクトンに悪影響を及
ぼさない限り、医薬に用いられる種々の添加剤を用いる
こともできる０例えば、賦形剤、安定剤としては、マン
ニトール、乳糖、”マルチドース、デキストラン、澱粉
類、ポリエチレングリコールなと、防腐剤としテハ、塩
化ペンザルフニウム、ベンジルアルコール、パラベン類
、無痛化剤としては、ポリソルベート類、脂肪酸エステ
ル類などが使用される。When preparing the drug, it can be in the form of an injection, powder, granule, tablet, tablet, or the like. In addition, 4-acetamido-4-hydroxy- which is an active ingredient of the antitumor agent of the present invention
Various additives used in pharmaceuticals may be used as long as they do not have an adverse effect on 2-buteonic acid-γ-lactone.For example, excipients and stabilizers include mannitol, lactose, multidose, Dextran, starch, polyethylene glycol, etc. are used as preservatives, Teha, penzalfnium chloride, benzyl alcohol, parabens, and as soothing agents, polysorbates, fatty acid esters, etc. are used.
また量刑の基剤としては、脂肪酸トリグリセリド、ポリ
エチレングリフール、ポリビニールアルコールなどが用
いられる。In addition, fatty acid triglycerides, polyethylene glyfur, polyvinyl alcohol, etc. are used as sentencing bases.
［発明の効果］
本発明の抗腫瘍剤の有効成分である４−アセタミド−４
−ヒドロキシ−２−ブテオニックアシッド−γ−ラクト
ンは、マウス白血病細胞、ヒドロ肺癌ＫＢ細砲に対し、
抗ｍｆＲ作用を示し、更に、ヒト白血病細胞を分化させ
、抗腫瘍剤として、有効であることが示唆される。[Effect of the invention] 4-acetamide-4, which is an active ingredient of the antitumor agent of the present invention
-Hydroxy-2-buteonic acid-γ-lactone is effective against murine leukemia cells and hydrolung cancer KB guns.
It is suggested that it exhibits anti-mfR activity, differentiates human leukemia cells, and is effective as an antitumor agent.
［実施例］
次に本発明を、試験例、実施例をもって具体的に説明す
る。[Example] Next, the present invention will be specifically explained using test examples and examples.
試験例１ （マウス白血病培養細胞Ｐ３８８およびＬ−
１２１０に対する増殖阻害作用）
（検体）製造例１で得られた白色板状結晶１０１を１ｍ
Ｑのエタノールに溶解し、目的濃度となるように無菌生
理食塩水にて希釈し、その５０ＰＪ１を検体として用い
た。Test Example 1 (Mouse leukemia cultured cells P388 and L-
Growth inhibitory effect on 1210) (Sample) 1 m of white plate-like crystals 101 obtained in Production Example 1
50PJ1 was dissolved in ethanol and diluted with sterile physiological saline to the desired concentration, and the resulting 50PJ1 was used as a sample.
（使用した培養液） ； ＲＰＭＩ−１６４０培地（
試験方法）： 上記培養液で、Ｐ２Ｓ５およびＬ−１２
１０＃Ｉ胞をｌＸｌ０’／ｍＱとし、ファルコン社製の
径３５ｆｆｆｌｌの６穴シヤーレに２ｒｔｔＱずツ分注
し、次いで検体を添加し、３７℃、５％次酸ガスインキ
ュベーター内で培養した。(Culture solution used); RPMI-1640 medium (
Test method): With the above culture solution, P2S5 and L-12
10#I cells were adjusted to 1X10'/mQ and dispensed in 2rttQ portions into a 6-hole plate made by Falcon Corporation with a diameter of 35ffll. Then, the specimen was added and cultured at 37° C. in a 5% hydrogen chloride gas incubator.
３日間培養を続けたのち、細胞数を測定し、増殖阻害率
は次式
を用いて算出し、試料濃度と阻止率のグラフから、ＩＣ
０値（５０％阻害のための濃度）を求めた。After continuing the culture for 3 days, the number of cells was measured, and the growth inhibition rate was calculated using the following formula, and from the graph of sample concentration and inhibition rate, the IC
A zero value (concentration for 50% inhibition) was determined.
（結果）；表１に示した。(Results): Shown in Table 1.
表１
試験例２（ヒドロ肺癌ＫＢ細胞に対する増殖阻害効果）
（検体）製造例１で得られた白色板状結晶１０■を１ｍ
ｌのジメチルスルホキシドに溶解し、目的濃度となるよ
うに無菌生理食塩水にて希釈し、その５０−を検体とし
て用いた。Table 1 Test Example 2 (Proliferation inhibitory effect on hydrolung cancer KB cells) (Sample) 1 m of white plate-like crystals obtained in Production Example 1
1 of dimethyl sulfoxide, diluted with sterile physiological saline to reach the target concentration, and the 50-ml solution was used as a sample.
（使用した培養液）； イーグルＭＥＭ培地（試験方法
）； 上記培養液で、ＫＢｍＮを１×１０’／ｍＱとし
、ファルコン社製の径３５■の６穴シヤーレに２ｍｌず
つ分注し、３７℃、５％Ｊ［ガスインキュベーター内で
一日培養し、次いで検体を添加し、更に３日間培養を続
けた。(Culture solution used); Eagle MEM medium (test method); The above culture solution was used to adjust KBmN to 1 x 10'/mQ, and dispensed 2ml each into a 6-hole shear dish with a diameter of 35cm manufactured by Falcon, and incubated at 37°C. , 5% J [The cells were cultured in a gas incubator for one day, then the specimen was added, and the culture was continued for an additional 3 days.
その後、生細胞数を測定し、試料濃度と阻止率のグラフ
からＩＣ，ｓ値を求めた。Thereafter, the number of viable cells was measured, and the IC,s value was determined from a graph of sample concentration and inhibition rate.
（結果）；表２に示した。(Results): Shown in Table 2.
表２
試験例３ （ヒト前骨髄性白血病細胞ＨＬ−６０に対す
る分化誘導作用）
（検体）製造例１で得られた白色板状結晶１０■を１ｍ
ｌのエタノールに溶解し、目的濃度となるように無菌生
理食塩水にて希釈し、その５０ＰＪ１を検体として用い
た。Table 2 Test Example 3 (Differentiation-inducing effect on human promyelocytic leukemia cells HL-60) (Sample) 1 m of white plate-like crystals obtained in Production Example 1
1 of ethanol, diluted with sterile physiological saline to reach the target concentration, and the resulting 50PJ1 was used as a sample.
（使用した培養液）； ＲＰＭＩ−１６４０培地（試
験方法）； 上記培養液で、ＨＬ−６０ｍ泊をｌＸｌ０
’／ｍｌとし、ファルコン社製の径３５■の６穴シヤー
レに２ｍｌずつ分注し、次いで検体を添加し、３７°Ｃ
，５％炭酸ガスインキュベーター内で３日間培養を続け
、分化誘導率を測定した６分化誘導率は、ＮＥＴ還元能
の測定法キャンサー リサーチ（Ｃａｎｃｅｒ Ｒｅ５
ｅｒａｃｈ ）第１４２巻、′第６４５頁、１９８２年
］に準じて算出した。(Culture solution used); RPMI-1640 medium (test method); With the above culture solution, HL-60m
'/ml, and dispensed 2ml each into a 6-hole 35cm diameter plate made by Falcon, then added the sample and heated at 37°C.
, The differentiation induction rate was measured after culturing in a 5% carbon dioxide incubator for 3 days.The differentiation induction rate was determined using Cancer Research (Cancer Re5
Erach) Vol. 142, 'Page 645, 1982].
（結果）；表３に示した。(Results): Shown in Table 3.
表３
試験例４（マウス白血病Ｌ−１２１０細胞に対する抗腫
瘍作用）
試験動物）；６週令のＣＤＦ、雌性マウスを１群８匹用
いた。対照群は１群２０匹である。Table 3 Test Example 4 (Antitumor Effect on Mouse Leukemia L-1210 Cells) Test Animals: Eight 6-week-old CDF female mice were used per group. The control group consisted of 20 animals per group.
（検体）製造例１で得られた白色板状結晶１０■を０．
５％アラビアゴム／生理食塩水で目的濃度となるように
希釈し、その２００４を検体として用いた。(Sample) 10 cm of white plate-like crystals obtained in Production Example 1 were collected at 0.
It was diluted with 5% gum arabic/physiological saline to the desired concentration, and 2004 was used as a sample.
（試験方法”）； ＣＤＦＩ雌性マウスの腹腔内にＬ−
１２１０細砲を１×１０″／マウスを接種し、翌日から
１日１回検体を腹腔内に５日間連続投与した。延命効果
の判定は、検体処置群および無処置群の平均生存日数（
それぞれＴ、Ｃ）からＴ／ＣＸ１００（％）を計算した
。(Test method); L-
1210 cannon was inoculated at 1 x 10''/mouse, and from the next day, the specimen was intraperitoneally administered once a day for 5 consecutive days. The survival effect was evaluated by the average survival days (
T/CX100 (%) was calculated from T and C), respectively.
（結果）；表４に示した。(Results): Shown in Table 4.
表４
試験例５（急性毒性試験）
７週令のウィスター系ラット（体重１４９〜１６０ｇ）
７匹を１群として試験に供した。Table 4 Test Example 5 (Acute Toxicity Test) 7 week old Wistar rats (body weight 149-160 g)
Seven animals were used in the test as one group.
製造例１で得られた白色板状結晶を０．５％アラビアゴ
ムに懸濁した液を前記ラットに腹腔内投与し、投与後７
日間の経過を観察した結果そのＬＤｌ。値は３０■／ｋ
ｇ以上であった。A suspension of the white plate-like crystals obtained in Production Example 1 in 0.5% gum arabic was intraperitoneally administered to the rats, and 7 days after administration.
As a result of observing the passage of days, the LDl. The value is 30■/k
It was more than g.
実施例１
４−アセタミド−４−ヒドロキシ−２−ブチオニツタア
シッド−７−ラクトンの６ｇを細末とし、これを乳糖３
０ｇおよびステアリン酸マグネシュウム２０ｇと混合し
、この混合物を単発式スラッグ打錠機にて打錠して直径
２０１ｍ１重量約２．３ｇのスラッグ錠を作り、これを
オシレーターにて破砕し、整粒、篩別して２０〜５０メ
ツシユの粒子を得た。Example 1 6 g of 4-acetamido-4-hydroxy-2-butionitta acid-7-lactone was made into fine powder, and this was mixed with lactose 3
0 g and 20 g of magnesium stearate, and this mixture was compressed using a single-shot slug tablet machine to make slug tablets with a diameter of 201 m and a weight of approximately 2.3 g. This was crushed using an oscillator, sized, and sieved. Separately, particles of 20 to 50 meshes were obtained.
本顆粒剤は１ｇ中に４−アセタミド−４−ヒドロキシ−
２−ブチオニツタアシッド−７−ラクトン１００ｎｔを
含有している。This granule contains 4-acetamido-4-hydroxy-
Contains 100 nt of 2-butionitta acid-7-lactone.
実施例２
４−アセタミド−４−ヒドロキシ−２−ブテオニックア
シッド−γ−ラクトンの顆粒１１００Ｉｌ１を硬カプセ
ルに充填してカプセル剤を得た。Example 2 Granules 1100I1 of 4-acetamido-4-hydroxy-2-buteonic acid-γ-lactone were filled into hard capsules to obtain capsules.
実施例３
４−アセタミド−４−ヒドロキシ−２−ブテオニックア
シッド−γ−ラクトン０，２ｇを注射用蒸留水ＩＰに溶
解し、等張化した後、アンプルに封入した０本注射剤１
ｍ１ｌは４−アセタミド−４−ヒドロキシ−２−ブテオ
ニックアシッド−γ−ラクトン０．２■を含んでいる。Example 3 0.2 g of 4-acetamido-4-hydroxy-2-buteonic acid-γ-lactone was dissolved in distilled water for injection IP, made isotonic, and then sealed in an ampoule.
ml contains 0.2 ml of 4-acetamido-4-hydroxy-2-buteonic acid-γ-lactone.
Claims (1)
クアシッド−γ−ラクトンを有効成分とする抗腫瘍剤。1) An antitumor agent containing 4-acetamido-4-hydroxy-2-buteonic acid-γ-lactone as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62100440A JPS63267718A (en) | 1987-04-23 | 1987-04-23 | Antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62100440A JPS63267718A (en) | 1987-04-23 | 1987-04-23 | Antitumor agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63267718A true JPS63267718A (en) | 1988-11-04 |
Family
ID=14273997
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62100440A Pending JPS63267718A (en) | 1987-04-23 | 1987-04-23 | Antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63267718A (en) |
-
1987
- 1987-04-23 JP JP62100440A patent/JPS63267718A/en active Pending
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