JPS6329888B2 - - Google Patents
Info
- Publication number
- JPS6329888B2 JPS6329888B2 JP57226915A JP22691582A JPS6329888B2 JP S6329888 B2 JPS6329888 B2 JP S6329888B2 JP 57226915 A JP57226915 A JP 57226915A JP 22691582 A JP22691582 A JP 22691582A JP S6329888 B2 JPS6329888 B2 JP S6329888B2
- Authority
- JP
- Japan
- Prior art keywords
- psof
- general formula
- positive number
- value
- polysilsesquioxane
- 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
Links
- 229920000734 polysilsesquioxane polymer Polymers 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 12
- -1 polysiloxane Polymers 0.000 claims description 10
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 9
- 229960002949 fluorouracil Drugs 0.000 claims description 9
- 229920001296 polysiloxane Polymers 0.000 claims description 9
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 5
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 238000000034 method Methods 0.000 description 11
- 230000001093 anti-cancer Effects 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 206010003445 Ascites Diseases 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000000862 absorption spectrum Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229910019440 Mg(OH) Inorganic materials 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229910018557 Si O Inorganic materials 0.000 description 1
- 208000009971 Walker Carcinoma 256 Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000002940 repellent Effects 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- LIVNPJMFVYWSIS-UHFFFAOYSA-N silicon monoxide Inorganic materials [Si-]#[O+] LIVNPJMFVYWSIS-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Silicon Polymers (AREA)
Description
本発明は、一般式
（但し、Ｙはアルカリ金属、アルカリ土類金属、
Ｈ原子又はNH4原子団を示し、ｌは１ないし20
の整数、ｍは４〜40の正の数、ｎは10〜90の正の
数である）で表わされるポリシルセスキオキサ
ン、および該ポリシルセスキオキサンの製造方法
および該ポリシルセスキオキサンを有効成分とす
る制癌剤に関する。
従来、ポリシルセスキオキサンの一部は、
The present invention is based on the general formula (However, Y is an alkali metal, an alkaline earth metal,
Indicates H atom or NH 4 atomic group, l is 1 to 20
m is a positive number of 4 to 40, n is a positive number of 10 to 90), a method for producing the polysilsesquioxane, and a method for producing the polysilsesquioxane The present invention relates to an anticancer drug containing San as an active ingredient. Traditionally, some polysilsesquioxanes are
【式】更に略記すればO1.5SiR（但
しＲは１価の有機基を表わす）で示されるシルセ
スキオキサンを繰返し単位とした高分子物質とし
て知られている。また該高分子物質はモデル的に
は下記式
で示される一般に梯子状又は籠状の骨格構造を有
する重合体化合物であることが知られていて、撥
水処理剤、潤滑剤、触媒等として広く利用されて
いる。
本発明者らは、各種のポリシルセスキオキサン
を合成し、それらについて種々の生理活性に関す
る研究を行つて来た。
その結果、新規なポリシルセスキオキサンが優
れた生理活性、殊に制癌活性を有することを見出
し、本発明を完成するに至つた。
本発明で提案するポリシルセスキオキサン新規
な化合物である。即ち、該ポリシルセスキオキサ
ンは一般式、
（但し、Ｙはアルカリ金属、アルカリ土類金属、
Ｈ原子又はNH4原子団を示し、ｌは１ないし20
の整数、ｍは４〜40の正の数、ｎは10〜90の正の
数である）で表わされるポリシルセスキオキサン
（以下PSOFと略記する場合もある）である。本
発明のPSOFは例えば、以下の化学分析および機
器分析によつて正確に同定できる。
(i) 先ず、元素分析を行うことによつて、Ｃ、
Ｈ、Ｎ、Si、Ｆの元素の重量％が求められる。
またこれらの各元素の重量％の和を100より減
じることにより、酸素元素の重量％が算出でき
る。
(ii) 更に該試料について、臭化カリウム錠剤法又
はヌジヨール混合法により、赤外吸収スペクト
ルを測定できる。
但し、該PSOFの赤外吸収スペクトルについて
は、一般式で表わしているｍとｎとの比率（ｎ／
ｍ値）、および一般式で表わしている−CO2Yが
カルボン酸であるかカルボン酸の塩であるかによ
り、吸収位置や吸収強度は若干変化する。通常、
該PSOFの赤外吸収スペクトルについては、650
cm-1、450cm-1に於ける５−フルオロウラシルに
基づく吸収帯と、1240cm-1〜940cm-1に於けるSi
−Ｃ、Si−Ｏに基づく幅広い吸収帯および1700cm
-1付近のカルボニルに基づく吸収帯により、その
構造を決定することが出来る。
更に、該PSOFの化学構造は、原料である一般
式[Formula] Further abbreviated as O 1.5 SiR (where R represents a monovalent organic group), it is known as a polymeric substance having a repeating unit of silsesquioxane. In addition, the model of the polymer substance is the following formula: It is known that it is a polymer compound generally having a ladder-like or cage-like skeleton structure, and is widely used as a water repellent agent, a lubricant, a catalyst, etc. The present inventors have synthesized various polysilsesquioxanes and conducted research on their various physiological activities. As a result, the inventors discovered that the novel polysilsesquioxane has excellent physiological activity, particularly anticancer activity, and completed the present invention. Polysilsesquioxane is a novel compound proposed in the present invention. That is, the polysilsesquioxane has the general formula: (However, Y is an alkali metal, an alkaline earth metal,
Indicates H atom or NH 4 atomic group, l is 1 to 20
m is a positive number of 4 to 40, n is a positive number of 10 to 90) (hereinafter sometimes abbreviated as PSOF). PSOFs of the invention can be accurately identified, for example, by the following chemical and instrumental analyses. (i) First, by conducting elemental analysis, C,
The weight percentages of the elements H, N, Si, and F are determined.
Furthermore, by subtracting the sum of the weight percent of each of these elements from 100, the weight percent of the oxygen element can be calculated. (ii) Furthermore, the infrared absorption spectrum of the sample can be measured by the potassium bromide tablet method or the nujiol mixing method. However, regarding the infrared absorption spectrum of the PSOF, the ratio of m and n (n/
m value) and whether -CO 2 Y represented by the general formula is a carboxylic acid or a salt of a carboxylic acid, the absorption position and absorption intensity change slightly. usually,
For the infrared absorption spectrum of the PSOF, 650
cm -1 , absorption band based on 5-fluorouracil at 450 cm -1 and Si at 1240 cm -1 to 940 cm -1
-Broad absorption band based on C, Si-O and 1700cm
Its structure can be determined by the absorption band based on the carbonyl near -1 . Furthermore, the chemical structure of the PSOF is based on the general formula of the raw material.
【式】（但しＸはハ
ロゲン原子を示し、ｌは１ないし20の整数を示
す）で表わされるポリシロキサン化合物の骨格構
造と全くよく対応するものである。
即ち該PSOFは、原料であるポリシロキサン化
合物の−COX基（但しＸはハロゲン原子を示す）
の一部がカルボキシル基となり、一部が５−フル
オロウラシルの１位と酸アミド結合をした化合物
である。従つて、原料となるポリシロキサン化合
物の構造を確認、同定しておけば、PSOFの化学
構造を同定するのは極めて容易となる。
上記原料となるポリシロキサン化合物の構造に
ついては既に公知で、例えば特開昭56−97229号
に記載されているので、そのまゝ利用することが
出来る。
該PSOFは、その分子構造にカルボキシル基を
有するため、親水性を有する。即ち、前記ｎ／ｍ
値が小さくなる程親水性は増加し、ｎ／ｍ値が大
きくなる程親水性は減少する。又、カルボキシル
基は、Na（Na）、Ｋ（K）等のアルカリ金属
の塩、Ca（1/2Ca）、Mg（1/2Mg）等の
アルカリ土類金属の塩、又はアンモニウム
（NH4）塩の形になると親水性が増す。この様
に該PSOFはｎ／ｍ値、PH等によつて、水に対す
る溶解度に差が出る。
該PSOFの利用方法、利用目的、剤形等によつ
て、好ましいｎ／ｍ値のものが適宜選択できる。
即ち、ｎ／ｍ値が小さいものは、水に溶け易く生
理食塩水にも均一に溶解する。又ｎ／ｍ値が大の
ものは、例えば５−フルオロウラシルによる制癌
効果が発現し易くなる。そこで、これらの性質を
兼ね備えたｎ／ｍ値のものが、その都度選択され
ればよい。
該PSOFの代表的な性状を以下に例記する。
(1) 無定形の白色固体状高分子体であり、通常粉
砕して粉体として取り扱われる。
(2) 一般の有機溶媒には、ほとんどあるいは全く
溶けない。
(3) 室温に於ては充分安定であるが、180℃以上
の高温に於ては熱分解する傾向にある。
(4) 分子量は400ないし40000である。
(5) 通常、水和物として存在する。
本発明の該PSOFの製造方法は特に限定的では
ないがその代表的な製造方法を例示すれば以下の
様にして合成される。
例えば、一般式
It completely corresponds to the skeletal structure of the polysiloxane compound represented by the formula: (where X represents a halogen atom and l represents an integer from 1 to 20). That is, the PSOF is a -COX group (X represents a halogen atom) of a polysiloxane compound that is a raw material.
It is a compound in which a part of is a carboxyl group and a part has an acid amide bond with the 1-position of 5-fluorouracil. Therefore, if the structure of the raw material polysiloxane compound is confirmed and identified, it will be extremely easy to identify the chemical structure of PSOF. The structure of the polysiloxane compound used as the raw material is already known, and is described, for example, in JP-A-56-97229, so it can be used as is. Since the PSOF has a carboxyl group in its molecular structure, it has hydrophilicity. That is, the n/m
The smaller the value, the more hydrophilicity increases, and the larger the n/m value, the less hydrophilicity. In addition, the carboxyl group is a salt of an alkali metal such as Na (Na) or K (K), a salt of an alkaline earth metal such as Ca (1/2Ca) or Mg (1/2Mg), or ammonium (NH 4 ). In salt form, it becomes more hydrophilic. As described above, the solubility of PSOF in water varies depending on the n/m value, pH, etc. A preferable n/m value can be selected as appropriate depending on the method of use, purpose of use, dosage form, etc. of the PSOF.
That is, substances with a small n/m value are easily soluble in water and uniformly dissolved in physiological saline. Furthermore, when the n/m value is large, the anticancer effect of, for example, 5-fluorouracil is more likely to occur. Therefore, a material having an n/m value that has both of these properties may be selected each time. Typical properties of the PSOF are illustrated below. (1) It is an amorphous white solid polymer and is usually crushed and handled as a powder. (2) Little or no solubility in common organic solvents. (3) Although it is sufficiently stable at room temperature, it tends to thermally decompose at high temperatures of 180°C or higher. (4) Molecular weight is 400 to 40,000. (5) Usually exists as a hydrate. Although the method for producing the PSOF of the present invention is not particularly limited, a typical method for producing it is synthesized as follows. For example, the general formula
【式】
（但し、Ｘはハロゲン原子を示し、ｌは１ないし
20の整数を示す）で表わされるポリシロキサン化
合物と５−フルオロウラシルとを非プロトン性極
性溶媒の存在下に反応させ、更に加水分解する方
法によつて合成される。
尚上記一般式中、Ｘはハロゲン原子であり、
Cl、Br、Ｉ又はＦであるが特にCl、Brは好適に
使用される。またｌはその数値が大きくなると反
応性が劣つたり、工業的でなかつたりするので一
般には１〜20好ましくは１〜10の整数であるのが
好的である。
原料であるポリシロキサン化合物は一般式
[Formula] (However, X represents a halogen atom, and l is 1 or
It is synthesized by a method in which a polysiloxane compound represented by (representing an integer of 20) and 5-fluorouracil are reacted in the presence of an aprotic polar solvent and further hydrolyzed. In the above general formula, X is a halogen atom,
Among them, Cl, Br, I or F, particularly Cl and Br are preferably used. In addition, if the value of l becomes large, the reactivity becomes poor or the reaction is not suitable for industrial use. The raw material polysiloxane compound has the general formula
更に得られたポリシルセスキオキサンの一部を
1.16ｇ取り出し、このものに10％KOHメタノー
ル性水溶液20mlを加えて、50℃にて６時間撹拌し
た。そうすると５−フルオロウラシルが加水分解
された。この遊離した５−フルオロウラシルを回
収する目的で、まず反応溶液に濃HClを加えてPH
＜２とした。次にCH3OH−H2Oとを減圧にて除
去すると、白色固体が得られた。この固体を減圧
乾燥した後、Ｎ，Ｎ−ジメチルホメムアミドを10
mlづつ20回加えて、未反応の５−フルオロウラシ
ルの抽出操作を行つた。抽出溶液からＮ，Ｎ−ジ
メチルホルムアミドを減圧除去し、得られた白色
固体を氷水1.0mlで３回洗浄して、この中に含ま
れる無機塩を除去した。
こうして、白色固体0.49ｇが得られた。このも
のの元素分析値および赤外吸収スペクトル、質量
分析スペクトルは、５−フルオロウラシルのもの
と一致した。
実施例 ２
実施例１で得られたPSOFを1.2ｇづつ４分配
し、その各々について、それぞれ0.1N−NaOH
水溶液、0.1N−KOH水溶液、0.1N−Ca（OH）2水
溶液、0.1N−Mg（OH）2水溶液中で50℃にて２時
間撹拌した。
該PSOFは、それぞれ水に不溶性を示し、反応
溶液を冷却した後、過、水洗、減圧乾燥するこ
とにより、該PSOFの各種の金属塩を得ることが
出来た。この結果を表(1)に示す。
Furthermore, a part of the obtained polysilsesquioxane
1.16g was taken out, 20ml of 10% KOH methanolic aqueous solution was added thereto, and the mixture was stirred at 50°C for 6 hours. Then, 5-fluorouracil was hydrolyzed. In order to recover this liberated 5-fluorouracil, firstly, concentrated HCl was added to the reaction solution and the pH was
<2. Next, CH 3 OH-H 2 O was removed under reduced pressure to obtain a white solid. After drying this solid under reduced pressure, 10% of N,N-dimethylhomemamide was added.
ml was added 20 times to extract unreacted 5-fluorouracil. N,N-dimethylformamide was removed from the extracted solution under reduced pressure, and the resulting white solid was washed three times with 1.0 ml of ice water to remove inorganic salts contained therein. Thus, 0.49 g of a white solid was obtained. The elemental analysis value, infrared absorption spectrum, and mass spectrometry spectrum of this product were consistent with those of 5-fluorouracil. Example 2 The PSOF obtained in Example 1 was divided into four portions of 1.2 g each, and 0.1N-NaOH was added to each portion.
The mixture was stirred at 50° C. for 2 hours in an aqueous solution, a 0.1N-KOH aqueous solution, a 0.1N-Ca(OH) 2 aqueous solution, and a 0.1N-Mg(OH) 2 aqueous solution. Each of the PSOFs was insoluble in water, and various metal salts of the PSOFs could be obtained by cooling the reaction solution, filtering, washing with water, and drying under reduced pressure. The results are shown in Table (1).
【表】【table】
【表】
実施例 ３
原料であるポリシロキサン化合物が以下の表(2)
に示すものであること以外は、実施例(1)と同じ反
応および後処理を行つてポリシルセスキオキサン
を得た。この結果を表(2)に示す。[Table] Example 3 The raw material polysiloxane compound is shown in the table (2) below.
Polysilsesquioxane was obtained by carrying out the same reaction and post-treatment as in Example (1), except for the following. The results are shown in Table (2).
【表】
実施例 ４
溶媒が表(3)に示すものである事以外は、実施例
１と同じ方法によりポリシルセスキオキサンを合
成した。溶媒の種類により、得られた生成物の
ｎ／ｍ値が異なつた。この時の結果を表(3)に示
す。[Table] Example 4 Polysilsesquioxane was synthesized in the same manner as in Example 1, except that the solvent was as shown in Table (3). The n/m value of the obtained product varied depending on the type of solvent. The results at this time are shown in Table (3).
【表】
実施例 ５
原料であるポリシロキサン化合物の粒径が異な
る事以外は、実施例１と同じ方法により、ポリシ
ルセスキオキサンを合成した。粒径によりｎ／ｍ
値が異なつたものが得られた。この結果を表(4)に
示す。[Table] Example 5 Polysilsesquioxane was synthesized by the same method as in Example 1, except that the particle size of the raw material polysiloxane compound was different. n/m depending on particle size
Different values were obtained. The results are shown in Table (4).
【表】
実施例 ６
実施例４で得たｎ／ｍ値1.63のポリシルセスキ
オキサンを界面活性剤ツイーン80を含む生理食塩
水に加えて規定量の試料を含む懸濁液あるいは均
一溶液とし、ポリシルセスキオキサンの濃度の異
なる液を３種類作成した。
この試料溶液を用いて体重20ｇ前後のCDF1系
マウスの雄６匹および雌２匹の腹腔内に注射投与
して20日間試験を行ない、急性毒性値（LD50）
をリツチフイールド−ウイルコクソンの方法によ
り求めた所2350mg／Kgであつた。
実施例 ７
実施例４で得られたｎ／ｍ値1.63のPSOFを用
いて、マウスのエールリツヒ腹水癌に対する抗癌
活性を試験した。
即ち、該PSOFを前記実施例６に記載した方法
で調整し、該試料をエールリツヒ癌細胞５×106
個を腹水内に移植したスイスマウス（雄）６匹に
対して、腹腔内に９日間連続投与した。
その60日間にわたる延命効果（Ｔ／Ｃ％）の結
果を表(5)に示す。
但し、
Ｔ／Ｃ（％）
＝比較群の平均生存日数（MST）／対照群の平均生存
日数（MST）×100（％）[Table] Example 6 Polysilsesquioxane with an n/m value of 1.63 obtained in Example 4 was added to physiological saline containing surfactant Tween 80 to form a suspension or homogeneous solution containing a specified amount of sample. Three types of liquids with different concentrations of polysilsesquioxane were prepared. This sample solution was intraperitoneally injected into 6 male and 2 female CDF 1 mice weighing around 20 g and tested for 20 days to determine the acute toxicity value (LD 50 ).
The amount was determined by the Richfield-Wilcoxon method and was 2350 mg/Kg. Example 7 Using PSOF with an n/m value of 1.63 obtained in Example 4, anticancer activity against Ehrlichi's ascites carcinoma in mice was tested. That is, the PSOF was prepared by the method described in Example 6 above, and the sample was injected into 5×10 6 Ehrlichi cancer cells.
The drug was administered intraperitoneally for 9 consecutive days to 6 Swiss mice (male) in which the cells were implanted into the ascites. The results of the survival effect (T/C%) over 60 days are shown in Table (5). However, T/C (%) = Mean survival days of comparison group (MST) / Mean survival days of control group (MST) x 100 (%)
【表】
実施例 ８
実施例４で得られたｎ／ｍ値1.63のPSOFを、
前記実施例６に記載したのと同じ方法で調整し、
このものを、ウオーカーカルシノサルコーマ256
癌細胞を腹水に１×105個移植したスプラグド−
レイ系ラツト（雄）６匹に対して腹腔内投与し
た。投与は５日間連続して行い、２ケ月間にわた
つて延命効果（Ｔ／Ｃ％）を調べた。この結果を
表(6)に示す。[Table] Example 8 The PSOF with n/m value 1.63 obtained in Example 4 was
Prepared in the same manner as described in Example 6 above,
This thing, Walker carcinosarcoma 256
Spragard transplanted 1 x 10 5 cancer cells into ascites
The drug was administered intraperitoneally to 6 male Ray rats. Administration was carried out for 5 consecutive days, and the survival effect (T/C%) was investigated over 2 months. The results are shown in Table (6).
【表】
実施例 ９
実施例４で得られたｎ／ｍ値1.63のPSOFを、
前記実施例６に記載したのと同じ方法で調整し
た。該試料をP388リンパ白血病癌細胞106個を腹
腔内に移植したCDF1系マウス（雄）６匹の腹腔
内に９日間連続投与した。
30日間にわたる延命効果（Ｔ／Ｃ％）を表(7)に
示す。[Table] Example 9 The PSOF with n/m value 1.63 obtained in Example 4 was
Prepared in the same manner as described in Example 6 above. The sample was continuously administered intraperitoneally for 9 days to 6 CDF 1 mice (male) in which 10 6 P388 lympholeukemia cancer cells were intraperitoneally implanted. Table (7) shows the survival effect (T/C%) over 30 days.
【表】
実施例 10
実施例１および２で得られた表(8)に示す各種の
PSOFについて、マウスのエールリツヒ腹水癌に
対する抗癌活性を試験した。
抗癌活性の測定方法は、実施例７に記載した方
法と同一である。
この結果を表(8)に示す。[Table] Example 10 The various types shown in Table (8) obtained in Examples 1 and 2
PSOF was tested for anticancer activity against Ehrlichi's ascites carcinoma in mice. The method for measuring anticancer activity is the same as the method described in Example 7. The results are shown in Table (8).
【表】【table】
【表】
実施例 11
実施例３で得られた表(9)に示す各種のPSOFに
ついてマウスのエールリツヒ腹水癌に対する抗癌
活性を試験した。
抗癌活性の測定方法は、実施例７に記載した方
法と同一である。この結果を表(9)に示す。[Table] Example 11 The various PSOFs shown in Table (9) obtained in Example 3 were tested for anticancer activity against Ehrlichi's ascites carcinoma in mice. The method for measuring anticancer activity is the same as the method described in Example 7. The results are shown in Table (9).
Claims (1)
Ｈ原子又はNH4原子団を示し、ｌは１ないし20
の整数、ｍは４〜40の正の数、ｎは10〜90の正の
数である）で表わされるポリシルセスキオキサ
ン。 ２ 一般式 （但し、Ｘはハロゲン原子を示し、ｌは１ないし
20の整数を示す）で表わされるポリシロキサン化
合物および５−フルオロウラシルとを非プロトン
性極性溶媒の存在下に反応させ、次いで加水分解
処理することを特徴とするポリシルセスキオキサ
ンの製造方法。 ３ 一般式 （但し、Ｙはアルカリ金属、アルカリ土類金属、
Ｈ原子又はNH4原子団を示し、ｌは１ないし20
の整数、ｍは４〜40の正の数、ｎは10〜90の正の
数である）で表わされるポリシルセスキオキサン
を有効成分とする制癌剤。[Claims] 1. General formula (However, Y is an alkali metal, an alkaline earth metal,
Indicates H atom or NH 4 atomic group, l is 1 to 20
m is a positive number of 4 to 40, n is a positive number of 10 to 90). 2 General formula (However, X represents a halogen atom, and l is 1 to
1. A method for producing polysilsesquioxane, which comprises reacting a polysiloxane compound represented by (representing an integer of 20) with 5-fluorouracil in the presence of an aprotic polar solvent, followed by hydrolysis treatment. 3 General formula (However, Y is an alkali metal, an alkaline earth metal,
Indicates H atom or NH 4 atomic group, l is 1 to 20
m is a positive number of 4 to 40, n is a positive number of 10 to 90) as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57226915A JPS59120634A (en) | 1982-12-27 | 1982-12-27 | Polysilsesquioxane and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57226915A JPS59120634A (en) | 1982-12-27 | 1982-12-27 | Polysilsesquioxane and its production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59120634A JPS59120634A (en) | 1984-07-12 |
| JPS6329888B2 true JPS6329888B2 (en) | 1988-06-15 |
Family
ID=16852590
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57226915A Granted JPS59120634A (en) | 1982-12-27 | 1982-12-27 | Polysilsesquioxane and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59120634A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6210138A (en) * | 1985-07-06 | 1987-01-19 | Tokuyama Soda Co Ltd | Polysilsesquioxane |
| JP2012111933A (en) | 2010-11-02 | 2012-06-14 | Nitto Denko Corp | Thermoplastic silicone resin |
| JP5877701B2 (en) * | 2011-03-29 | 2016-03-08 | 日東電工株式会社 | Thermoplastic silicone resin |
| EP2567998A1 (en) * | 2011-09-09 | 2013-03-13 | Nitto Denko Corporation | Thermoplastic silicone resin |
| JP6488851B2 (en) | 2015-04-21 | 2019-03-27 | トヨタ紡織株式会社 | Manufacturing method of headrest |
-
1982
- 1982-12-27 JP JP57226915A patent/JPS59120634A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59120634A (en) | 1984-07-12 |
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