JPS62221696A - 1-beta-d-arabinofuranosylcytosine-5'-stearyl-phosphoric acid monosodium salt monohydrate - Google Patents
1-beta-d-arabinofuranosylcytosine-5'-stearyl-phosphoric acid monosodium salt monohydrateInfo
- Publication number
- JPS62221696A JPS62221696A JP61063963A JP6396386A JPS62221696A JP S62221696 A JPS62221696 A JP S62221696A JP 61063963 A JP61063963 A JP 61063963A JP 6396386 A JP6396386 A JP 6396386A JP S62221696 A JPS62221696 A JP S62221696A
- Authority
- JP
- Japan
- Prior art keywords
- stearyl
- monosodium salt
- type
- phosphoric acid
- crystals
- 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 title description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 title description 4
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 title 1
- 239000013078 crystal Substances 0.000 abstract description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- 238000003860 storage Methods 0.000 abstract description 3
- 229910019142 PO4 Inorganic materials 0.000 abstract description 2
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 238000002156 mixing Methods 0.000 abstract description 2
- 239000010452 phosphate Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 3
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 230000001143 conditioned effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000002441 X-ray diffraction Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 238000004455 differential thermal analysis Methods 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- -1 and prohanol Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- ZIRKHYMKGFNSKI-UHFFFAOYSA-M sodium;octadecyl hydrogen phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOP(O)([O-])=O ZIRKHYMKGFNSKI-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明の１−β−Ｄ−アラビノフラノシルシトシン−５
−ステアリルりん酸モノナトリウム塩・１水和物は経口
用抗腫瘍剤として期待されてるものである。Detailed Description of the Invention [Industrial Field of Application] 1-β-D-arabinofuranosylcytosine-5 of the present invention
-Stearyl phosphate monosodium salt monohydrate is expected to be an oral antitumor agent.
１−β−Ｄ−アラビノシルシトシンー５−ステアリルり
ん酸ナトリウム塩（以下アラシチジン−５−ステアリル
りん酸ナトリウム塩という。）の製造方法は特公昭５５
−４９５８８号に開示されている。この方法はアラシチ
ジン−５′−ステアリンりん酸（遊離酸）を水中でｐＨ
７，０に調整した後、濃縮し、エタノールを加えて沈澱
を析出させ、アラシチジン−５−ステアリンりん酸ナト
リウム塩とするものである。The method for producing 1-β-D-arabinosylcytosine-5-stearyl phosphate sodium salt (hereinafter referred to as aracytidine-5-stearyl phosphate sodium salt) is disclosed in Japanese Patent Publication No. 55
-49588. This method involves adding alacitidine-5'-stearic phosphate (free acid) to pH
After adjusting the concentration to 7.0, it is concentrated, and ethanol is added to precipitate it to obtain alacitidine-5-stearin phosphate sodium salt.
しかしながら、上記特公昭５５−４９５８８号に開示さ
れた方法によって得られたアラシチジン−５′−ステア
リンりん酸ナトリウム塩は粉宋状でＸ線回折を行うと明
確な回折ピークを示さない無晶形である。（第３図参照
）また、このナトリウム塩を加湿条件下例えば２５℃、
９３％の相対湿度下に放置すると、１２％〜１３％程度
重量の増加があり、著しい吸湿性を示す。またこのもの
を２５℃相対湿度７５％の条件下に放置した場合１４ケ
月後、含量が９３．７％に低下し、さらに５０℃相対湿
度７４％の条件では３ケ月後含量が５８．６％と著しく
低下し、分屏物として１−β−Ｄ−アラビノフラノシル
ウラシル−５−ステアリルりん酸ナトリウム塩が生成す
ることが判明した。これらのことはこのアラシチジン−
５′−ステアリルりん酸ナトリウム塩を医薬品製剤とす
る場合、吸湿性を配慮した製造を特殊に考える必要があ
り、また流通においても厳重な包装を要する。−男女定
性が悪いため有効期限の非常に短い薬剤となり、事実上
医薬品として市場に供し得ない。However, the aracitidine-5'-stearin phosphate sodium salt obtained by the method disclosed in the above-mentioned Japanese Patent Publication No. 55-49588 is in the form of powder and is in an amorphous form that does not show clear diffraction peaks when subjected to X-ray diffraction. . (See Figure 3) Also, this sodium salt may be mixed under humidified conditions, for example at 25°C.
When left under a relative humidity of 93%, the weight increases by about 12% to 13%, indicating significant hygroscopicity. Furthermore, if this product was left at 25°C and a relative humidity of 75%, the content decreased to 93.7% after 14 months, and when further left at 50°C and a relative humidity of 74%, the content decreased to 58.6% after 3 months. It was found that 1-β-D-arabinofuranosyluracil-5-stearyl phosphate sodium salt was formed as a fraction. These things are true for this alacitidine.
When 5'-stearyl phosphate sodium salt is used as a pharmaceutical preparation, special consideration must be given to manufacturing with hygroscopicity in mind, and strict packaging is also required for distribution. - Due to the poor gender identity, the drug has a very short shelf life, making it practically impossible to market it as a drug.
本発明者らは種々検討の結果、下記式で示されるアラシ
チジン−５−ステアリルりん酸モノナトリウム塩・１水
和物は吸湿性もなく安定性もよいことを見い出し、本発
明を完成本発明のアラシチジン−５７−ステアリルりん
酸モノナトリウム塩・１水和物はその製造法によりβ型
及びβ型の２種の結晶形態をとる。As a result of various studies, the present inventors found that aracitidine-5-stearyl phosphate monosodium salt monohydrate represented by the following formula has no hygroscopicity and good stability, and completed the present invention. Aracytidine-57-stearyl phosphate monosodium salt monohydrate takes two types of crystal forms, β-type and β-type, depending on the manufacturing method.
この１水和物のβ型及びβ型結晶の理化学的性質は次の
通りである。The physicochemical properties of the β-form and β-form crystals of this monohydrate are as follows.
１、 Ｘ線回折パターン
Ｎ１箔フイルターをしたＣｕ放射装置及びシンチレーシ
ョンカウンター検出機を備えた理学電機Ｘ線回折装置に
よって測定した粉末Ｘ線回折パターンを第１図（β型）
および第２図（β型）にその解析結果を第１表に示す。1. X-ray diffraction pattern Figure 1 shows the powder X-ray diffraction pattern measured by a Rigaku X-ray diffraction device equipped with a Cu radiation device equipped with an N1 foil filter and a scintillation counter detector (β type).
and FIG. 2 (β type), and the analysis results are shown in Table 1.
第１表
（電源 Ｃｕ：Ｎ１，３０ＫＶ、２０ｍＡλ＝１．５４
０５）２、熱分析
島津ＤＴ−３０型熱分析装置によって測定した示差熱分
析ではβ型は１２８℃において吸熱を示し、ｒ型は９８
℃及び１１３℃において吸熱を示し、結晶水の脱離が認
められる。Table 1 (Power supply Cu: N1, 30KV, 20mAλ=1.54
05) 2. Thermal Analysis According to differential thermal analysis measured with a Shimadzu DT-30 thermal analyzer, the β type shows an endotherm at 128°C, and the r type shows an endotherm at 98°C.
It exhibits endotherm at 113°C and 113°C, and desorption of water of crystallization is observed.
そして熱重量分析の結果、β型及びβ型とも３％の重量
減少が認められた。そのパターンを第４図（β型）及び
第５図（β型）に示す。As a result of thermogravimetric analysis, a weight decrease of 3% was observed for both the β and β types. The patterns are shown in FIG. 4 (β type) and FIG. 5 (β type).
３、吸湿性
５０℃で減圧（５ｍｍｇＨｇ）乾燥したβ型結晶及び５
０℃で減圧（５ｍｍＨｇ ）乾燥したβ型結晶を、温度
２５℃、相対湿度９３％の条件下に３日間放置したとこ
ろ、β型及びβ型とも重量変化はみられず、吸湿性を有
しない。3. Hygroscopic β-type crystals dried at 50°C under reduced pressure (5 mmgHg) and 5
When β-form crystals dried at 0°C under reduced pressure (5 mmHg) were left for 3 days at a temperature of 25°C and a relative humidity of 93%, no change in weight was observed for both the β-form and the β-form, and they had no hygroscopicity. .
水分定量カールフィシャー法により水分の定量を行った
結果、β型結晶は３．０％、ｒ型結晶は２．９２％であ
り理論値、２．９２％とよく一致した。Moisture Quantification The moisture content was determined by the Karl Fischer method, and the results were 3.0% for β-type crystals and 2.92% for r-type crystals, which agreed well with the theoretical value of 2.92%.
本発明におけるアラシチジン−５′−ステアリルりん酸
ナトリウム塩１水和物は次のようにして製造される。Alacitidine-5'-stearyl phosphate sodium salt monohydrate in the present invention is produced as follows.
アラシチジン−５′−ステアリルりん酸を水に溶解又は
懸濁させ、水酸化ナトリウムを加えて、よく攪拌混合し
、ｐＨを好ましくは１０〜１３、より好ましくは１０．
３〜１２に調整した後、減圧濃縮乾固するか水と混合す
る有機溶媒例えばエタノール、メタノール、プロハノー
ルのような低級アルコール、アセトンメチルエチルケト
ンのよ５なケトン類、テトラヒドロフラン、ジオキサン
などの還状エーテル類を添加して、アラシチジン−５′
−ステアリルりん酸モノナトリウム塩を析出させる。Alacitidine-5'-stearyl phosphoric acid is dissolved or suspended in water, sodium hydroxide is added, and the mixture is thoroughly stirred to adjust the pH to preferably 10 to 13, more preferably 10.
After adjusting to 3 to 12, organic solvents such as lower alcohols such as ethanol, methanol, and prohanol, ketones such as acetone, methyl ethyl ketone, and cyclic ethers such as tetrahydrofuran and dioxane are concentrated to dryness under reduced pressure or mixed with water. by adding alacitidine-5'
- Precipitating stearyl phosphate monosodium salt.
この得られたウェットの状態のナトリウム塩を３〜５倍
量のエタノールに懸濁させ、約１時間以上、好ましくは
約２時間〜６時間程度混合した後、濾過により結晶を分
離し、室温〜１００℃で乾燥することにより、β型の１
水和物の結晶を得ることができる。The obtained wet sodium salt is suspended in 3 to 5 times the amount of ethanol, mixed for about 1 hour or more, preferably about 2 to 6 hours, and then the crystals are separated by filtration. By drying at 100℃, β-type 1
Hydrate crystals can be obtained.
またγ型の１水和物の結晶は上記β型結晶をメタノール
に加熱溶解し、徐冷して結晶を析出させるか、上記のウ
ェットの状態のモノナト１八ウム塩を減圧下に乾燥させ
た後、メタノールに加熱溶解して徐冷してモノナトリウ
ム塩を析出させ戸数し、減圧下１００℃以下で乾燥する
ことにより得られる。In addition, the γ-type monohydrate crystals were obtained by heating and dissolving the β-type crystals in methanol and slowly cooling them to precipitate the crystals, or by drying the wet mononato 1-octium salt above under reduced pressure. Thereafter, the monosodium salt is precipitated by heating and dissolving in methanol and cooling slowly, followed by drying at 100° C. or lower under reduced pressure.
本発明のアラシチジン−５′−ステアリルりん酸モノナ
トリウム塩・１水和物は前記のように吸湿性を示さず、
かつ下記に示すように保存安定性も良好なものである。The alacitidine-5'-stearyl phosphate monosodium salt monohydrate of the present invention does not exhibit hygroscopicity as described above,
Moreover, as shown below, the storage stability is also good.
保存安定性試験（苛酷安定性試験）
本発明におけるアラシチジン−５７−ステアリルりん酸
モノナトリウム塩・１水和物を６５℃、相対湿度７３％
で１カ月保存し、その含量変化を調べた。Storage stability test (severe stability test) Aracytidine-57-stearyl phosphate monosodium salt monohydrate according to the present invention was stored at 65°C and relative humidity 73%.
The sample was stored for one month and changes in its content were examined.
その結果、β型結晶及びγ型結晶とも１力月後において
もその含量は９９．９％（対イニシャル含量）であり、
はとんど分解が起らず安定なものであった。As a result, the content of both β-type crystals and γ-type crystals was 99.9% (relative to the initial content) even after one month.
It was stable with almost no decomposition.
次に本発明を実施例により具体的に示す。Next, the present invention will be specifically illustrated by examples.
実施例１゜
特公昭５５−４９５８８号の実施例４の方法により、ア
ラシチジン−５′−ステアリルりん酸を得た。Example 1 Aracytidine-5'-stearyl phosphoric acid was obtained by the method of Example 4 of Japanese Patent Publication No. 55-49588.
このアラシチジン−５７−ステアリルりん酸１０ｇに水
５Ｑｍｌを加えた後、攪拌しながら、水酸化ナトリウム
を加えて、溶液のｐＨを１０．５に調整した。After adding 5 Qml of water to 10 g of this aracytidine-57-stearyl phosphoric acid, sodium hydroxide was added while stirring to adjust the pH of the solution to 10.5.
３０分間攪拌混合した後、エタノール（９５％）を１２
０ ｍｌ添加して、ナトＩＪウム塩の結晶を析出させた
。この結晶を戸数して、ウェットの状態（水分含量約２
０％）のナトＩＪウム塩８．５ｇを３０ｍ１のエタノー
ルに懸濁した。９０分間撹拌したの後、結晶を戸数し、
減圧下４０℃で乾燥し、β型結晶の１水和物を得た。After stirring and mixing for 30 minutes, add ethanol (95%) to 12
0 ml was added to precipitate crystals of sodium sodium salt. This crystal is dried in a wet state (moisture content approximately 2
8.5 g of Na-IJum salt (0%) was suspended in 30 ml of ethanol. After stirring for 90 minutes, the crystals were separated,
It was dried at 40° C. under reduced pressure to obtain a monohydrate of β-type crystals.
このもののＸ線回折は第１図及び第１表に示した通りで
あり、その示差熱分析は第４図の通りであった。The X-ray diffraction of this product was as shown in FIG. 1 and Table 1, and the differential thermal analysis was as shown in FIG. 4.
実施例２゜
実施例１で得られたウェットの状態のモノナト１八ウム
塩を、減圧下６０℃にて１６時間乾燥した。Example 2 The wet mononato-1-octium salt obtained in Example 1 was dried at 60°C under reduced pressure for 16 hours.
この乾燥品５ｇをメタノール２０ｍ１に６０℃に加熱溶
解させた。完全に溶解後徐冷して結晶を析出させ、戸数
し、６０℃で減圧乾燥、ｒ型結晶を得た。得られた結晶
のＸ線回折は第２図及び第１表に示した通りであり、そ
の示差熱分析は第５図の通りであった。5 g of this dried product was dissolved in 20 ml of methanol by heating at 60°C. After complete dissolution, the mixture was slowly cooled to precipitate crystals, dried several times at 60° C. under reduced pressure, and R-type crystals were obtained. The X-ray diffraction of the obtained crystal was as shown in FIG. 2 and Table 1, and the differential thermal analysis was as shown in FIG.
第１図及び第２図はアラシチジン−５′−ステアリルり
ん酸モノナトリウム塩・１水和物のＸ線回折図であり、
第１図はβ型結晶のもの、第２図はγ型結晶のものであ
る。第３図は公知方法で得られた非晶形のＸ線回折図で
ある。
また第４図及び第５図はアラシチジン−５′−ステアリ
ルりん酸モノナトリウム塩・１水和物の示差熱分析図で
あり、第４図がβ型結晶のものであり、第５図がγ型結
晶のものである。第６図は公知方法で得られた示差熱分
析図である。Figures 1 and 2 are X-ray diffraction patterns of alacitidine-5'-stearyl phosphate monosodium salt monohydrate;
FIG. 1 shows a β-type crystal, and FIG. 2 shows a γ-type crystal. FIG. 3 is an X-ray diffraction diagram of an amorphous form obtained by a known method. Figures 4 and 5 are differential thermal analysis diagrams of alacitidine-5'-stearyl phosphate monosodium salt monohydrate, with Figure 4 showing the β-type crystal and Figure 5 showing the γ-type crystal. It is of type crystal. FIG. 6 is a differential thermal analysis diagram obtained by a known method.
Claims (1)
テアリルりん酸モノナトリウム塩・１水和物。1,1-β-D-arabinofuranosylcytosine-5-stearyl phosphate monosodium salt monohydrate.
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61063963A JPS62221696A (en) | 1986-03-24 | 1986-03-24 | 1-beta-d-arabinofuranosylcytosine-5'-stearyl-phosphoric acid monosodium salt monohydrate |
| ES198787104071T ES2031462T3 (en) | 1986-03-24 | 1987-03-19 | PROCEDURE TO PRODUCE 1-B-D-ARABINOFURANOSILCITOSINA-5'-STERARILFOSFATO MONOSODICO AND MONOHIDRATO OF THE SAME, AND PHARMACEUTICAL COMPOUND THAT CONTAINS THIS LAST. |
| EP87104071A EP0239015B1 (en) | 1986-03-24 | 1987-03-19 | Process for producing 1-beta-d-arabinofuranosylcytosine-5'-stearylphosphate monosodium salt and monohydrate thereof, and pharmaceutical composition containing the latter |
| DE8787104071T DE3773716D1 (en) | 1986-03-24 | 1987-03-19 | METHOD FOR PRODUCING MONOSODIUM SALTS AND THEIR MONOHYDRATE OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE-5'STEARYLPHOSPHATE AND THE PHARMACEUTICAL COMPOSITION CONTAINING THEM. |
| CA000532597A CA1270820A (en) | 1986-03-24 | 1987-03-20 | PROCESS FOR PRODUCING 1-.beta.-D- ARABINOFURANOSYLCYTOSINE-5'-STEARYLPHOSPHATE MONOSODIUM SALT AND MONOHYDRATE THEREOF |
| HU871247A HU196429B (en) | 1986-03-24 | 1987-03-20 | Process for preparing monosodium salts of 1-beta-d-arabinofuranozylcytozine-5'-stearyl phosphate and the monohydrate of this salt |
| AU70475/87A AU592165B2 (en) | 1986-03-24 | 1987-03-20 | Process for producing 1-beta-D-arabinofuranosylcytosine-5- stearylphosphate monosodium salt and monohydrate thereof |
| KR1019870002697A KR910008801B1 (en) | 1986-03-24 | 1987-03-23 | Process for producing 1-beta-arabino-furanosylcytosine-5-stearylphosphate monosodium salt and monohydrate thereof |
| US07/028,951 US4812560A (en) | 1986-03-24 | 1987-03-23 | Process for producing 1-β-D-arabinofuranosylcytosine-5'-stearylphosphate monosodium salt and monohydrate thereof |
| US07/399,303 US5049663A (en) | 1986-03-24 | 1989-08-25 | Process for producing 1-β-D-arabinofuranosylcytosine-5'-stearylphosphate monosodium salt and monohydrate thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61063963A JPS62221696A (en) | 1986-03-24 | 1986-03-24 | 1-beta-d-arabinofuranosylcytosine-5'-stearyl-phosphoric acid monosodium salt monohydrate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62221696A true JPS62221696A (en) | 1987-09-29 |
| JPS6330315B2 JPS6330315B2 (en) | 1988-06-17 |
Family
ID=13244463
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61063963A Granted JPS62221696A (en) | 1986-03-24 | 1986-03-24 | 1-beta-d-arabinofuranosylcytosine-5'-stearyl-phosphoric acid monosodium salt monohydrate |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62221696A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994003183A1 (en) * | 1992-08-10 | 1994-02-17 | Nippon Kayaku Kabushiki Kaisha | Medicinal composition for inhibiting cancer metastasis to liver and medicinal composition for curing hepatoma |
-
1986
- 1986-03-24 JP JP61063963A patent/JPS62221696A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994003183A1 (en) * | 1992-08-10 | 1994-02-17 | Nippon Kayaku Kabushiki Kaisha | Medicinal composition for inhibiting cancer metastasis to liver and medicinal composition for curing hepatoma |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6330315B2 (en) | 1988-06-17 |
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