JPS58210010A - Antitumor agent - Google Patents
Antitumor agentInfo
- Publication number
- JPS58210010A JPS58210010A JP9231882A JP9231882A JPS58210010A JP S58210010 A JPS58210010 A JP S58210010A JP 9231882 A JP9231882 A JP 9231882A JP 9231882 A JP9231882 A JP 9231882A JP S58210010 A JPS58210010 A JP S58210010A
- Authority
- JP
- Japan
- Prior art keywords
- lactone
- antitumor agent
- hydroxyvitamin
- cells
- vitro
- 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.)
- Granted
Links
Landscapes
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は25−ヒドロキシビタミンI)、−26,23
−ラクトンを含有する抗腫瘍剤に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention provides 25-hydroxyvitamin I), -26,23
- Concerning antitumor agents containing lactones.
現在用いられている抗悪性腫瘍剤としてはアルキル化剤
、代謝拮抗剤、抗生剤、植物アルカロイド剤、免疫療法
剤等あるが、そのうち癌細胞に対してin vltro
にて殺細胞効果を示す薬剤は副作用も強いものが多い。Currently used antineoplastic agents include alkylating agents, antimetabolites, antibiotics, plant alkaloids, and immunotherapeutic agents.
Many of the drugs that exhibit cell-killing effects also have strong side effects.
本発明者らは従来よシ生体内物質についての研究を行っ
てきた結果、25−ヒドロキシビタミンn1−26.2
3−ラクトン(以下、本物質又は25−(OH) −D
J−26,23−1actone と略称する)73
月nvitroで癌細胞に対して殺細胞効果を示すこと
を知見した。The present inventors have been conducting research on substances in the body of shrimp, and as a result, we found that 25-hydroxyvitamin n1-26.2
3-lactone (hereinafter referred to as this substance or 25-(OH)-D
J-26,23-1actone)73
It was found that the drug had a cytocidal effect on cancer cells in vitro.
本物質は次のような構造を有し、例えばいる。This substance has the following structure, for example.
−tacton*
−1actone −1ac
tone258−(OH)−Dl−26,23R−1a
c t o n。-tacton* -1actone -1ac
tone258-(OH)-Dl-26,23R-1a
ct on.
本発明者らは、in vltroでヒト白血病由来のに
−562、ヒト骨髄連山来のLICR−LON−HMy
2細胞を用いて本物質の抗腫瘍効果を調べたところ腫瘍
細胞増殖抑制作用或いは殺細胞効果が認められた。さら
にマウス、ラットを宿主として行った試験でも抗腫瘍効
果が認められた。The present inventors performed in vitro experiments on human leukemia-derived NI-562 and human bone marrow-derived LICR-LON-HMy.
When the antitumor effect of this substance was investigated using 2 cells, tumor cell growth suppressive effect or cell killing effect was observed. Furthermore, antitumor effects were observed in tests conducted using mice and rats as hosts.
本物質は25R−COH)−Dl−26,23S −1
actone :25R−(OH)−DB−26,23
R−1acton@: 25B−(OH)−Ds−26
,238−1actone : 25S−(OH:)−
Da−26,23R〜1actone又はそれらの2種
以上の混合物であってもよいが、特に2 s R−(O
H) −DB−26,23S −1actoneが好ま
しい。本発明の抗腫瘍剤は活性成分として上記の物質を
含有し、下記に示すごとき陣々の製剤形態で用いられる
。本発明の抗腫瘍剤は腹腔内等の非経口的経路で投与さ
れるが経口的に投与され得る特徴を有する。This substance is 25R-COH)-Dl-26,23S -1
actone:25R-(OH)-DB-26,23
R-1acton@: 25B-(OH)-Ds-26
,238-1actone: 25S-(OH:)-
Da-26,23R-1actone or a mixture of two or more thereof may be used, but especially 2s R-(O
H) -DB-26,23S-1 actone is preferred. The antitumor agent of the present invention contains the above-mentioned substances as active ingredients, and is used in various formulations as shown below. The antitumor agent of the present invention is administered by a parenteral route such as intraperitoneally, but has the characteristic that it can be administered orally.
本物質を有効成分とする製剤は錠剤、散剤、顆粒剤、坐
剤、カプセル剤、アルコール溶液剤、油性溶液剤、水性
懸濁液剤などの投与形態で用いられる。又油性溶媒とし
ては、中級脂肪酸のトリグリセライドエステル、コーン
油、綿実油、落花生油、魚肝油、油状エステルなどが用
いられる。又カカオ油、グリセリン等も好ましい。その
他の成分として乳糖、でんぷん、メルク、ステアリン酸
マグネシウム、ソルビン酸、ソルビン酸の宝、糖又はそ
の誘導体、アルコール、生理食塩水、界面活性剤、酸化
防止剤等を本物質と併用し得る。Preparations containing this substance as an active ingredient are used in dosage forms such as tablets, powders, granules, suppositories, capsules, alcoholic solutions, oily solutions, and aqueous suspensions. As the oily solvent, triglyceride esters of intermediate fatty acids, corn oil, cottonseed oil, peanut oil, fish liver oil, oily esters, etc. are used. Also preferred are cacao oil and glycerin. Other ingredients such as lactose, starch, Merck, magnesium stearate, sorbic acid, sorbic acid, sugar or derivatives thereof, alcohol, physiological saline, surfactants, antioxidants, etc. may be used in combination with this substance.
本物質は、単位投与形態の中に0.00002〜4重1
%、好ましくは0.0002〜1重葉%含有し得る。又
、本物質は成人に対し1日嶺り0.1μり〜10000
μり、打首しくは0.5〜1o o Ox9投与する。This substance may be present in unit dosage form from 0.00002 to 4 times 1
%, preferably 0.0002 to 1%. In addition, this substance has a daily dose of 0.1μ to 10,000 for adults.
Administer 0.5 to 1000x9 by smearing or decapitation.
実施例1
ヒト白血病由来のに−562であり、10%牛脂児」m
清添加RPMI 1640培地に浮遊状で増殖する1n
vltro培養株を用いて実験を行った。それぞれの
細胞数がI X 10” / 1ntとなるように培地
に懸濁させ、その5ゴをシャーレに分注し、37℃5%
炭酸ガス含有空気雰囲気の培養器中にて培養した。25
ft−(OH)−DB−26,238−1actone
ldジメチルスルホキシド(以下DMSOと略す)
に溶解し、0M80の最終濃度か0.5容量%で25R
−(OH)−DB−26,238−1aeton・が所
定の濃度になるようにシャーレに添加し、培養3日後に
トリバンプルー染色し、総生細胞数を針側した。結果を
第1表に示す。Example 1 Ni-562 derived from human leukemia and containing 10% beef tallow
1n grown in suspension in RPMI 1640 medium supplemented with supernatant.
Experiments were performed using vltro cultures. Suspend each cell in a medium so that the number of cells is I x 10" / 1 nt, dispense 5 cells into a petri dish, and incubate at 37°C 5%.
The cells were cultured in an incubator with an air atmosphere containing carbon dioxide gas. 25
ft-(OH)-DB-26,238-1actone
ld dimethyl sulfoxide (hereinafter abbreviated as DMSO)
25R at a final concentration of 0M80 or 0.5% by volume.
-(OH)-DB-26,238-1aeton· was added to a petri dish at a predetermined concentration, and after 3 days of culture, it was stained with trivan blue and the total number of viable cells was counted on the needle side. The results are shown in Table 1.
第 1 表
増殖抑制率は溶媒(0M80)投与群と比較した場合の
%を示す。Table 1 Growth inhibition rate shows the percentage when compared with the vehicle (0M80) administration group.
上記の如く、25R−(OH) −Dl−26,238
−1actoneはs00ng/−の濃度でに−562
に対しては68%の細胞増殖抑制率を示した。As above, 25R-(OH)-Dl-26,238
-1actone is -562 at a concentration of s00ng/-
showed a cell proliferation inhibition rate of 68%.
実施例2
ヒトミエローマ由来のLICR−LON−HMy2であ
り、10%牛脂児血清添加RPMI 164G培地に浮
遊状で増殖するln vitro培養株を用いて実験を
行った。それぞれの細胞数がlXl0”/−となるよう
に培地に懸濁させ、その5−をシャーレに分注し、37
℃5%炭酸ガス含有空気雰囲気の培養器中にて培養した
。25R−(OH)−D、−26,23S −1act
one はDM80に溶解し、抽定の濃度になるように
添加し、培養3日後にトリバンプルー染色し、総生細胞
数を計測した。結果を第2表に示す。Example 2 An experiment was conducted using an ln vitro culture strain that is human myeloma-derived LICR-LON-HMy2 and grows in suspension in RPMI 164G medium supplemented with 10% tallow serum. Suspend each cell in a medium so that the number of cells is 1X10"/-, dispense the 5-cells into a petri dish, and
The cells were cultured in an incubator with an air atmosphere containing 5% carbon dioxide at ℃. 25R-(OH)-D, -26,23S-1act
One was dissolved in DM80 and added to the extraction concentration, and after 3 days of culture, the cells were stained with Trivan blue and the total number of living cells was counted. The results are shown in Table 2.
第 2 表
増殖抑制率は溶媒(DM80 )投与群と比較した場合
の%を示す。Table 2 Growth inhibition rate shows the percentage when compared with the vehicle (DM80) administration group.
上記の如(,25R−(OH)−DB−26,23−1
actoneはs o o n 9/ml の濃度で
LICRに対しては71%の細胞増殖抑制率を示した。As above (,25R-(OH)-DB-26,23-1
Actone showed a 71% cell growth inhibition rate against LICR at a concentration of 9/ml.
実施例3
アルゴン・バブリング中で400W高圧水銀ランプで7
2時間照射して不純な反応性のパーオキシドを消失せし
めた中級脂肪酸のトリグリセライドエステルIKfに2
5R−(OH)−D、−26,238−1actone
5111pを溶解し、1カプセル中に25R−(O
H) Da 26.23S−1actone を0.
5μり含有するように下記剤皮成分を加温溶解し軟カプ
セル製造機を用いて常法によシ軟カプセル剤を作成した
。Example 3 7 with 400W high pressure mercury lamp in argon bubbling
Triglyceride ester IKf of intermediate fatty acids was irradiated for 2 hours to eliminate impure reactive peroxides.
5R-(OH)-D, -26,238-1actone
Dissolve 5111p and add 25R-(O
H) Da 26.23S-1actone at 0.
The following shell components were heated and dissolved so as to contain 5 μm, and soft capsules were prepared in a conventional manner using a soft capsule making machine.
剤皮処方例
ゼラチン 10重量部
グリセリン 2 〃
防贋剤(エチルパラベン)0.05 ttチタンホワ
イト 0.2〃
水 0.2//(最終形態に於ける重量部
)
同碌にして1カプセル中に1μり、2μq又は5μりを
含有するものをそれぞれ作成した。Shell formulation example Gelatin 10 parts by weight Glycerin 2 Anti-counterfeiting agent (ethylparaben) 0.05 tt Titanium White 0.2 Water 0.2 // (parts by weight in final form) Equal in 1 capsule Those containing 1μ, 2μq, or 5μ were respectively prepared.
55
Claims (1)
ラクトン を有効成分とする抗腫瘍剤。 12125−ヒドロキシビタミンD、−26,23−ラ
クトンが25R−ヒドロキシビタミンD、−26゜23
8−ラクトンであるととを特徴とする特許請求の範囲詔
1項に記載の抗腫瘍剤。(1) 25-hydroxyvitamin D, -26,23-
An antitumor agent containing lactone as an active ingredient. 12125-hydroxyvitamin D, -26,23-lactone is 25R-hydroxyvitamin D, -26°23
The antitumor agent according to claim 1, which is an 8-lactone.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9231882A JPS58210010A (en) | 1982-05-31 | 1982-05-31 | Antitumor agent |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9231882A JPS58210010A (en) | 1982-05-31 | 1982-05-31 | Antitumor agent |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS58210010A true JPS58210010A (en) | 1983-12-07 |
JPH0220612B2 JPH0220612B2 (en) | 1990-05-10 |
Family
ID=14051038
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP9231882A Granted JPS58210010A (en) | 1982-05-31 | 1982-05-31 | Antitumor agent |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS58210010A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1461044A4 (en) * | 2001-12-03 | 2007-06-13 | Novacea Inc | Pharmaceutical compositions comprising active vitamin d compounds |
-
1982
- 1982-05-31 JP JP9231882A patent/JPS58210010A/en active Granted
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1461044A4 (en) * | 2001-12-03 | 2007-06-13 | Novacea Inc | Pharmaceutical compositions comprising active vitamin d compounds |
Also Published As
Publication number | Publication date |
---|---|
JPH0220612B2 (en) | 1990-05-10 |
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