JPH0260648B2 - - Google Patents
Info
- Publication number
- JPH0260648B2 JPH0260648B2 JP55037150A JP3715080A JPH0260648B2 JP H0260648 B2 JPH0260648 B2 JP H0260648B2 JP 55037150 A JP55037150 A JP 55037150A JP 3715080 A JP3715080 A JP 3715080A JP H0260648 B2 JPH0260648 B2 JP H0260648B2
- Authority
- JP
- Japan
- Prior art keywords
- carboxylic acid
- thiazolidine
- compound
- group
- tumor
- 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.)
- Expired - Lifetime
Links
- -1 2-substituted thiazolidine-4-carboxylic acid Chemical class 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 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 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 150000003935 benzaldehydes Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000011081 inoculation Methods 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
- 239000000203 mixture Substances 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- APAUAYLVDHNFBF-UHFFFAOYSA-N 2-(2-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid Chemical compound N1C(C(=O)O)CSC1C1=CC=CC=C1O APAUAYLVDHNFBF-UHFFFAOYSA-N 0.000 description 1
- TWPYJYQNZHPNGQ-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid Chemical compound N1C(C(=O)O)CSC1C1=CC=C(O)C=C1 TWPYJYQNZHPNGQ-UHFFFAOYSA-N 0.000 description 1
- HTRWLFRKMUVNPG-UHFFFAOYSA-N 2-(4-methylphenyl)-1,3-thiazolidine-4-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1SCC(C(O)=O)N1 HTRWLFRKMUVNPG-UHFFFAOYSA-N 0.000 description 1
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 1
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- 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
- 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- 229960001674 tegafur Drugs 0.000 description 1
- 150000003548 thiazolidines Chemical class 0.000 description 1
- DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical class OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は抗腫瘍剤に関する。
従来アルデヒド類の抗腫瘍効果が検討されてい
るがアルデヒド類は一般に不安定で空気中の酸素
で酸化され易く、製剤化および、保存上の問題が
ある。
本発明者らはアルデヒド類とシステインから製
造されるチアゾリジン化合物について研究を重ね
た結果ベンズアルデヒド誘導体とシステインとを
反応させて得られる化合物に抗腫瘍作用のあるこ
とを発明し、さらに検討を加えて本発明を完成す
るに至つた。
本発明は、
式
K0021
（式中、Ｒはハロゲン、水酸基、低級アルコキシ
基または低級アルキル基を示す）で表わされる２
−置換チアゾリジン−４−カルボン酸よりなる抗
腫瘍剤である。
本発明に用いる２−置換チアゾリジン−４−カ
ルボン酸はジヨン・ウイレイ・アンド・サンズ・
インコーポレーテツド発行のケミストリー・オ
ブ・ジ・アミノ・アシツド第３巻1907頁の記載を
参考にして次のように合成した。
２−置換チアゾリジン−４−カルボン酸誘導体
の一般合成法。
0.4モル濃度の塩酸システイン水溶液100mlに20
（Ｗ／Ｕ）％の水酸化ナトリウムを加えてPH5.0と
し、これに0.4モルのベンズアルデヒド誘導体の
メチルアルコール溶液100mlを加えて、約40℃で
30分間かきまぜ、つぎに、冷却したのち析出した
結晶を取し、水、メチルアルコールまたは水−
メチルアルコールから再結晶させる。収率は50〜
80％を得る。
上記の方法において、ベンズアルデヒド誘導体
として、たとえば、
１ ２−ハイドロキシベンズアルデヒド、
２ ３−ハイドロキシベンズアルデヒド、
３ ４−ハイドロキシベンズアルデヒド、
４ ４−クロルベンズアルデヒド、
５ ４−フルオロベンズアルデヒド、
６ ４−メチルベンズアルデヒドおよび
７ ４−メトキシベンズアルデヒド
を用い、それぞれ次表１中に対応する番号を付し
て示す２−置換チアゾリジン−４−カルボン酸を
得た。
The present invention relates to antitumor agents. The antitumor effects of aldehydes have been studied in the past, but aldehydes are generally unstable and easily oxidized by oxygen in the air, causing problems in formulation and storage. As a result of repeated research on thiazolidine compounds produced from aldehydes and cysteine, the present inventors discovered that a compound obtained by reacting a benzaldehyde derivative with cysteine has an antitumor effect. The invention was completed. The present invention provides 2 represented by the formula K0021 (wherein R represents halogen, hydroxyl group, lower alkoxy group or lower alkyl group)
-An antitumor agent consisting of substituted thiazolidine-4-carboxylic acid. The 2-substituted thiazolidine-4-carboxylic acid used in the present invention is manufactured by John Wiley & Sons.
The synthesis was carried out as follows, with reference to the description in Chemistry of Di Amino Acids, Vol. 3, page 1907, published by Incorporated. General synthesis method for 2-substituted thiazolidine-4-carboxylic acid derivatives. 20 in 100 ml of 0.4 molar cysteine hydrochloride aqueous solution
Add (W/U)% sodium hydroxide to adjust the pH to 5.0, add 100 ml of methyl alcohol solution of 0.4 mol benzaldehyde derivative, and heat at about 40℃.
Stir for 30 minutes, then cool and collect the precipitated crystals and add water, methyl alcohol or water to the solution.
Recrystallize from methyl alcohol. Yield is 50~
Get 80%. In the above method, the benzaldehyde derivatives include, for example, 1 2-hydroxybenzaldehyde, 2 3-hydroxybenzaldehyde, 3 4-hydroxybenzaldehyde, 4 4-chlorobenzaldehyde, 5 4-fluorobenzaldehyde, 6 4-methylbenzaldehyde, and 7 4- Using methoxybenzaldehyde, 2-substituted thiazolidine-4-carboxylic acids, which are shown with corresponding numbers in Table 1 below, were obtained.
【表】
上記、表１に示した化合物は冷水に難溶である
が、アルカリ塩は易溶で、たとえば、水酸化ナト
リウム、水酸化カリウムまたは炭酸ナトリウムで
中和すると冷水にもよく溶ける。また、本化合物
は空気中で酸化されず安定である。
本発明の化合物は低毒性である。前記の化合物
TC−１およびTC−５について、それぞれ４週令
の雄性ICRマウス各30匹（５匹ずつ、６段階）を
用いて静脈注射による急性毒性を試験したところ
次表のとおり毒性がかなり低いことが確認され
た。
化合物 LD50（mg／Kg）
TC−１ 730−750
TC−５ 800−900
本化合物の制ガン作用について試験したところ
次に示すように著しい効果を有することが判明し
た。
方法として、４週令1CRマウス雄の右蹊部皮下
にエールリツヒ腹水腫瘍1.25×106細胞／0.2mlの
割合で生理食塩水に懸濁したものを接種した。
一方、本化合物を水中で水酸化ナトリウムによ
り溶解してPH7.0〜7.5の注射液とした。この注射
液と薬効を比較するために、すでに市販されてい
るフトラフール注射液を用いて、0.2〜0.25mlを
前記の接種されたマウスの接種部位にそれぞれ24
時間後より、毎日、９日間連続して注射した。マ
ウスは１群10匹とし、被検薬物群と対照群に分
け、被検薬物の本化合物はマウス体重１Kg当に換
算して、毎日本化合物400ｇ（400mg／Kg）投与、
さらに、薬効比較のためフトラフールは120mg／
Kg投与した。なお、対照群には無菌生理食塩水
0.2mlを同様に投与した。
効果判定法として、エールリツヒ腹水腫瘍細胞
接種後12日目に解部、腫瘍重量を測定し、腫瘍抑
制率（Ｔ／Ｃ）＝被検薬物群平均腫瘍重量／生食対照平
均腫瘍重量を求め
た結果を表２に示す。
表２ エールリツヒ結節腫瘍に対する２−置換チ
アゾリジン−４−カルボン酸の効果
被検薬物 腫瘍抑制率(T/C)
TC−１ 0.42
TC−２ 0.68
TC−３ 0.28
TC−４ 0.44
TC−５ 0.65
TC−６ 0.34
TC−７ 0.48
フトラフール 0.52
判定基準として応用薬理７巻1277頁（1973年）
に記載してある藤井らの方法を採用すると腫瘍抑
制率が0.50以下が有効、0.50〜0.70がやゝ有効、
0.70以上が無効と定めている。
上記の実験結果から明らかのように、２−置換
チアゾリジン−４−カルボン酸の本化合物は抗腫
瘍作用を示し、その作用は実験におけるような固
形型腫瘍に対しても強く発現し、たとえば消化器
系、呼吸器系その他の腫瘍に広く用いることが出
来る。
本発明の化合物は前記のように安定なので、賦
形剤と混合して顆粒に造粒し、カプセルに充填す
るかまたは錠剤に打錠して内服に供することが出
来る。上記の賦形剤としては、たとえば殿粉、乳
糖、マンニツトなどを用いることが出来る。ある
いはナトリウム塩、カリウム塩などの水溶性塩の
形で水溶液として注射に供することが出来る。注
射剤は皮下、筋肉内もしくは静脈内注射でもよ
い。
投与量は成人１日25−4000mgが好ましく、毒性
の現われない範囲で１日１〜数回に分けて投与す
ることが出来る。
実施例 １
注射剤
２−（２−ハイドロキシフエニル）チアゾリジ
ン−４−カルボン酸100mgを無菌的にバイアルに
入れて密栓し、つぎに、注射用溶解液として、塩
化ナトリウム600mgリン酸−水素ナトリウム500
mg、水酸化ナトリウム380mgを注射用蒸留水100ml
に溶かし、これを無菌過して、５ml用アンプル
に５mlづつに充填して熔閉する。バイヤル１個と
アンプル１本とを１セツトとする。用時溶解して
筋注または静注とする。
実施例 ２
錠剤
２−（４−ハイドロキシフエニル）チアゾリジン
−４−カルボン酸 100mg
乳 糖 80mg
デンプン 17mg
ステアリン酸マグネシウム ３mg
以上を１錠分の材料として常法により錠剤に成
型する。必要に応じ糖衣を付してもよい。
実施例 ３
カプセル剤
２−（４−メチルフエニル）チアゾリジン−４−
カルボン酸 100mg
乳 糖 50mg
結晶セルローズ 30mg
タルク ５mg
以上が１カプセル分となるように上記の比率で
各料を混合し、カプセル中に充填する。[Table] The compounds shown in Table 1 above are poorly soluble in cold water, but alkali salts are easily soluble, and when neutralized with, for example, sodium hydroxide, potassium hydroxide, or sodium carbonate, they dissolve well in cold water. Moreover, this compound is stable and is not oxidized in the air. The compounds of the invention have low toxicity. The above compound
TC-1 and TC-5 were tested for acute toxicity by intravenous injection using 30 4-week-old male ICR mice (5 mice each, 6 stages), and the toxicity was found to be quite low as shown in the table below. confirmed. Compound LD 50 (mg/Kg) TC-1 730-750 TC-5 800-900 When the anticancer effect of this compound was tested, it was found to have remarkable effects as shown below. As a method, Ehrlitsu ascites tumor suspended in physiological saline was inoculated subcutaneously in the right anus of a 4-week-old male 1CR mouse at a rate of 1.25 x 10 6 cells/0.2 ml. On the other hand, this compound was dissolved in water with sodium hydroxide to prepare an injection solution with a pH of 7.0 to 7.5. In order to compare the drug efficacy with this injection solution, we used a commercially available Futorafur injection solution and applied 0.2 to 0.25 ml to the inoculation site of the above-mentioned inoculated mice for 24 hours.
After that time, injections were given every day for 9 consecutive days. There were 10 mice in each group, and they were divided into a test drug group and a control group.
Furthermore, for comparison of drug efficacy, 120 mg of ftorafur/
Kg was administered. In addition, sterile physiological saline was used as a control group.
0.2 ml was administered in the same manner. As a method for evaluating efficacy, the tumor weight was measured on the 12th day after inoculation of Ehrlichi's ascites tumor cells, and the tumor suppression rate (T/C) = test drug group average tumor weight / saline control average tumor weight was calculated. are shown in Table 2. Table 2 Effect of 2-substituted thiazolidine-4-carboxylic acid on Ehrlichi's nodule tumor Test drug Tumor inhibition rate (T/C) TC-1 0.42 TC-2 0.68 TC-3 0.28 TC-4 0.44 TC-5 0.65 TC- 6 0.34 TC-7 0.48 Futhorafur 0.52 As a criterion Applied Pharmacology Vol. 7, p. 1277 (1973)
When using the method of Fujii et al. described in
A value of 0.70 or higher is defined as invalid. As is clear from the above experimental results, this compound of 2-substituted thiazolidine-4-carboxylic acid exhibits antitumor activity, and this activity is strongly expressed even against solid tumors such as those in the gastrointestinal tract. It can be widely used for tumors in the respiratory system, respiratory system, and other tumors. Since the compound of the present invention is stable as described above, it can be mixed with excipients, granulated, and filled into capsules or compressed into tablets for oral administration. Examples of the above-mentioned excipients include starch, lactose, mannitol, and the like. Alternatively, it can be injected as an aqueous solution in the form of water-soluble salts such as sodium salts and potassium salts. Injections may be administered subcutaneously, intramuscularly or intravenously. The preferred dosage for adults is 25-4000 mg per day, and it can be administered in one to several divided doses per day as long as no toxicity occurs. Example 1 Injection 100 mg of 2-(2-hydroxyphenyl)thiazolidine-4-carboxylic acid was aseptically put into a vial and the vial was tightly stoppered.Next, as an injection solution, 600 mg of sodium chloride and 500 mg of sodium phosphate-hydrogen were added.
mg, 380 mg of sodium hydroxide in 100 ml of distilled water for injection
The solution is sterilized, filled into 5 ml ampoules (5 ml each), and melted. One set includes one vial and one ampoule. Before use, dissolve and administer intramuscularly or intravenously. Example 2 Tablets 2-(4-hydroxyphenyl)thiazolidine-4-carboxylic acid 100 mg Lactose 80 mg Starch 17 mg Magnesium stearate 3 mg The above ingredients for one tablet are molded into tablets by a conventional method. May be coated with sugar if necessary. Example 3 Capsule 2-(4-methylphenyl)thiazolidine-4-
Carboxylic acid 100mg Lactose 50mg Crystalline cellulose 30mg Talc 5mg Mix each ingredient in the above ratio so that one capsule contains at least 1 capsule, and fill it into a capsule.
Claims (1)
基または低級アルキル基を示す） で表わされる２−置換チアゾリジン−４−カルボ
ン酸よりなる抗腫瘍剤。[Scope of Claims] 1. An antitumor agent comprising 2-substituted thiazolidine-4-carboxylic acid represented by the formula K0020 (wherein R represents a halogen, hydroxyl group, lower alkoxy group, or lower alkyl group).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3715080A JPS56133216A (en) | 1980-03-24 | 1980-03-24 | Antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3715080A JPS56133216A (en) | 1980-03-24 | 1980-03-24 | Antitumor agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56133216A JPS56133216A (en) | 1981-10-19 |
| JPH0260648B2 true JPH0260648B2 (en) | 1990-12-17 |
Family
ID=12489576
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3715080A Granted JPS56133216A (en) | 1980-03-24 | 1980-03-24 | Antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS56133216A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57128625A (en) * | 1981-01-30 | 1982-08-10 | Rikagaku Kenkyusho | Carcinostatic |
| DK2968346T3 (en) * | 2013-03-15 | 2024-05-06 | Cancer Research Tech Llc | Methods and compositions for modulating the gamma-glutamyl cycle |
| KR101793544B1 (en) | 2015-12-30 | 2017-11-03 | 엘에스산전 주식회사 | Transportation Device of Withdrawable Circuit Breaker |
-
1980
- 1980-03-24 JP JP3715080A patent/JPS56133216A/en active Granted
Non-Patent Citations (1)
| Title |
|---|
| J.MED.CHEM=1976 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56133216A (en) | 1981-10-19 |
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