JPH06179692A - 2'-deoxy-2'-methylidenecytidine anhydride crystal and its production - Google Patents
2'-deoxy-2'-methylidenecytidine anhydride crystal and its productionInfo
- Publication number
- JPH06179692A JPH06179692A JP33475792A JP33475792A JPH06179692A JP H06179692 A JPH06179692 A JP H06179692A JP 33475792 A JP33475792 A JP 33475792A JP 33475792 A JP33475792 A JP 33475792A JP H06179692 A JPH06179692 A JP H06179692A
- Authority
- JP
- Japan
- Prior art keywords
- deoxy
- methylidenecytidine
- crystal
- anhydrous
- 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
Landscapes
- Saccharide Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、抗腫瘍剤として有用な
２’−デオキシ−２’−メチリデンシチジン（以下、Ｄ
ＭＤＣと略す）の新規な無水物結晶およびその製造法に
関するものである。The present invention relates to 2'-deoxy-2'-methylidene cytidine (hereinafter referred to as D) which is useful as an antitumor agent.
The present invention relates to a novel anhydrous crystal of MDC) and a method for producing the same.
【０００２】[0002]
【従来の技術】ＤＭＤＣは下記構造式で表される化合物
であり、抗腫瘍作用、抗ウイルス作用を有する極めて有
用な化合物である（特開昭６３−２３０６９９号公報、
特開昭６３−２５８８１８号公報）。DMDC is a compound represented by the following structural formula and is a very useful compound having an antitumor action and an antiviral action (Japanese Patent Laid-Open No. 63-230699).
JP-A-63-258818).
【０００３】[0003]
【化１】 [Chemical 1]
【０００４】従来、ＤＭＤＣの結晶性物質としては、塩
酸塩結晶（特開昭６３−２３０６９９号公報）および二
水和物結晶（特開平３−２４０７９４号公報）が知られ
ており、ＤＭＤＣの無定形物質としては無定形無水物が
知られている（J. Med, Chem., 34, 2607-2615 (199
1))。しかしながら、塩酸塩結晶および無定形無水物
は、吸湿性、安定性、取扱性などの点で問題を有し、医
薬品原体として満足できるものではない。一方、二水和
物結晶は、塩酸塩結晶および無定形無水物の欠点を克服
できるものであることから、ＤＭＤＣの抗腫瘍剤として
の開発は主に二水和物結晶を中心に行われてきている。Conventionally, as crystalline substances of DMDC, hydrochloride crystals (JP-A-63-230699) and dihydrate crystals (JP-A-3-240794) are known, and DMDC-free crystals are known. Amorphous anhydride is known as a regular substance (J. Med, Chem., 34, 2607-2615 (199
1)). However, hydrochloride crystals and amorphous anhydrides have problems in hygroscopicity, stability, handleability, etc., and are not satisfactory as drug substances. On the other hand, since the dihydrate crystal can overcome the drawbacks of the hydrochloride crystal and the amorphous anhydrous, the development of DMDC as an antitumor agent has been mainly focused on the dihydrate crystal. ing.
【０００５】[0005]
【発明が解決しようとする課題】ＤＭＤＣ二水和物結晶
を抗腫瘍剤として開発しようとする場合、製剤の形態と
しては錠剤、散剤などの経口投与形態、注射剤などの非
経口投与形態などのさまざまな形態が考えられる。その
中でも経口投与形態は患者への苦痛も少なく優れた形態
であり、抗腫瘍剤を開発する場合も、経口投与剤は魅力
的な製剤形態である。経口投与剤として製剤化する際、
一般には微粉砕化された化合物を用いるのが望ましいと
されている。しかし、公知の二水和物結晶は、物理的な
粉砕に対して不安定で、微粉砕化するとその一部が溶融
し、溶融したものが粉砕室等に強固に付着するために、
目的とする微粉砕品の回収率が著しく低下するという問
題を有している。When DMDC dihydrate crystals are to be developed as an antitumor agent, the dosage form includes oral dosage forms such as tablets and powders, parenteral dosage forms such as injections, and the like. Various forms are possible. Among them, the oral administration form is an excellent form with less pain to the patient, and the oral administration form is an attractive formulation even when developing an antitumor agent. When formulating as an orally administered drug,
It is generally considered desirable to use finely divided compounds. However, the known dihydrate crystals are unstable with respect to physical crushing, and when finely pulverized, a part thereof is melted, and the melted matter adheres firmly to the crushing chamber, etc.,
There is a problem that the recovery rate of the target finely pulverized product is significantly reduced.
【０００６】本発明の目的は、良好な吸湿性、安定性、
取扱性を有し、かつ物理的な粉砕に対しても安定である
２’−デオキシ−２’−メチリデンシチジンを提供する
ことである。The object of the present invention is to obtain good hygroscopicity, stability,
The object of the present invention is to provide 2'-deoxy-2'-methylidene cytidine, which has handleability and is stable against physical grinding.
【０００７】[0007]
【課題を解決するための手段】本発明者らは、上述した
二水和物結晶の欠点を解決すべく鋭意検討した結果、Ｄ
ＭＤＣを有機溶媒に加温して溶解させた後にＤＭＤＣを
晶析させることにより、物理的な粉砕処理に対して安定
なＤＭＤＣ無水物結晶を得ることができることを見い出
し、本発明を完成させた。DISCLOSURE OF THE INVENTION As a result of intensive studies made by the present inventors to solve the above-mentioned drawbacks of dihydrate crystals, D
The present invention was completed by discovering that DMDC anhydrous crystals stable to physical pulverization treatment can be obtained by crystallizing DMDC after heating and dissolving MDC in an organic solvent.
【０００８】即ち、本発明は、新規なＤＭＤＣの無水物
結晶（以下、本発明化合物と称することもある）および
その微粉砕物に関するものである。また、本発明は、Ｄ
ＭＤＣの有機溶媒溶液からＤＭＤＣを晶析させることを
特徴とするＤＭＤＣ無水物結晶の製造法に関するもので
ある。That is, the present invention relates to a novel anhydrous crystal of DMDC (hereinafter sometimes referred to as the compound of the present invention) and a finely pulverized product thereof. The present invention also provides
The present invention relates to a method for producing anhydrous DMDC crystals, which comprises crystallizing DMDC from a solution of MDC in an organic solvent.
【０００９】本発明化合物は、典型的には下記の物理化
学的性質を有する。 水分含量：第１２改正日本薬局方に記載の方法により
測定した本発明化合物の水分含量は、通常０．２重量％
以下である。The compounds of the present invention typically have the following physicochemical properties. Water content: The water content of the compound of the present invention measured by the method described in the 12th revised Japanese Pharmacopoeia is usually 0.2% by weight.
It is the following.
【００１０】融点：第１２改正日本薬局方に記載の方
法により測定した本発明化合物の融点は、通常１８０〜
１８４℃、好ましくは１８１〜１８３℃である。Melting point: The melting point of the compound of the present invention measured by the method described in the 12th revised Japanese Pharmacopoeia is usually 180-
The temperature is 184 ° C, preferably 181 to 183 ° C.
【００１１】示差走査熱量分析：示差走査熱量分析装
置（セイコー電子工業：ＳＳＣ５８０ＤＳ）を用い、下
記の条件で測定した本発明化合物の吸熱ピークは、通常
１９４〜１９８℃、好ましくは１９５〜１９７℃に出現
する。 測定条件；試料約５ｍｇ、昇温速度５．０℃／分、対照
物質ＡｌDifferential scanning calorimetric analysis: The endothermic peak of the compound of the present invention measured by a differential scanning calorimeter (Seiko Denshi Kogyo: SSC580DS) under the following conditions is usually 194 to 198 ° C, preferably 195 to 197 ° C. Appear. Measurement conditions: Sample about 5 mg, heating rate 5.0 ° C / min, reference substance Al
【００１２】粉末Ｘ線回折：Ｘ線回折装置（島津製作
所：ＸＤ−６１０）を用い、下記の条件で測定した本発
明化合物の粉末Ｘ線回折スペクトル上の主要ピークは、
下記の回折角に出現する。 回折角２θ（°）：１１．２，１５．６，１８．５，１
９．０，２１．２，２２．５，２５．３および２７．２ 測定条件； Ｘ線チューブ：ターゲットＣｕ、４０ｋＶ、４０ｍＡ スリット：（ＳＳ）１ｄｅｇ、（ＤＳ）１ｄｅｇ、（Ｒ
Ｓ）０．３１ｍｍ スキャンモード：ＣＯＮＴＩ プレセットタイム：０．４（ｓ） ステップ幅：０６８３３０５（ｄｅｇ／ｓｔｅｐ） スキャンスピード：４（ｄｅｇ／分）Powder X-ray diffraction: Main peaks on the powder X-ray diffraction spectrum of the compound of the present invention measured using an X-ray diffractometer (XD-610 manufactured by Shimadzu Corporation) under the following conditions:
Appears at the diffraction angle below. Diffraction angle 2θ (°): 11.2, 15.6, 18.5, 1
9.0, 21.2, 22.5, 25.3 and 27.2 Measurement conditions; X-ray tube: target Cu, 40 kV, 40 mA Slit: (SS) 1 deg, (DS) 1 deg, (R
S) 0.31 mm Scan mode: CONTI Preset time: 0.4 (s) Step width: 0683305 (deg / step) Scan speed: 4 (deg / min)
【００１３】上記のような物性を有する本発明化合物
は、さらに以下に示すように物理的粉砕に対して安定で
あり、かつ吸湿性を示さないという特徴を有している。The compound of the present invention having the above-mentioned physical properties is further characterized in that it is stable against physical pulverization and does not exhibit hygroscopicity, as shown below.
【００１４】微粉砕試験 本発明化合物２５０ｇまたは二水和物結晶２２０ｇを超
微粉砕器を用いて粒径が０．１〜１０μｍになるように
粉砕した。その結果、二水和物結晶は、粉砕中にその一
部が溶融して粉砕器に付着・固化し、その付着量は運転
時間と共に増大し、目的とする微粉砕品を低収率でしか
得られなかった。これに対し、本発明化合物は、二水和
物結晶のように粉砕中に溶融しないので、微粉砕品をほ
ぼ定量的に得ることができた（表１参照）。なお、無定
形無水物を上記微粉砕試験に供してみたところ、無定形
無水物は下記試験に示すように吸湿性を有し、微粉砕す
ることはできなかった。Fine pulverization test 250 g of the compound of the present invention or 220 g of dihydrate crystals was pulverized by using an ultrafine pulverizer so as to have a particle size of 0.1 to 10 μm. As a result, part of the dihydrate crystals melts during pulverization and adheres to the pulverizer and solidifies, and the amount of adherence increases with the operating time, and the target finely pulverized product can be obtained only in a low yield. I couldn't get it. On the other hand, since the compound of the present invention does not melt during pulverization like a dihydrate crystal, a finely pulverized product could be obtained almost quantitatively (see Table 1). When the amorphous anhydride was subjected to the fine pulverization test, the amorphous anhydride had hygroscopicity as shown in the following test and could not be finely pulverized.
【００１５】[0015]
【表１】 [Table 1]
【００１６】吸湿試験 本発明化合物および無定形無水物を相対湿度５３％、温
度２５℃の条件下で放置し、吸湿による重量変化を測定
した。その結果、無定形無水物は吸湿し、１日で７．８
６％の重量増加を示した。一方、本発明化合物はほとん
ど吸湿せず、１日の重量増加はわずかに０．１４％であ
った（表２参照）。Moisture Absorption Test The compound of the present invention and the amorphous anhydride were allowed to stand under the conditions of relative humidity of 53% and temperature of 25 ° C., and weight change due to moisture absorption was measured. As a result, the amorphous anhydrous product absorbs moisture and is 7.8 per day.
It showed a 6% weight gain. On the other hand, the compound of the present invention hardly absorbed moisture, and the weight increase per day was only 0.14% (see Table 2).
【００１７】[0017]
【表２】 [Table 2]
【００１８】本発明化合物は、ＤＭＤＣの有機溶媒溶液
からＤＭＤＣを晶析させる方法により調製することがで
きる。The compound of the present invention can be prepared by crystallization of DMDC from a solution of DMDC in an organic solvent.
【００１９】ＤＭＤＣの有機溶媒溶液を調製する際に使
用されるＤＭＤＣとしては、従来公知の二水和物結晶お
よび無定形無水物のいずれの化合物も使用できる。二水
和物結晶または無定形無水物を溶解させる有機溶媒とし
ては、アルコール（メタノール、エタノール、プロパノ
ールなど）、ジオキサンおよびアセトニトリルからなる
群より選択される単一溶媒またはこれらの二種以上を混
合した混合溶媒を使用することができる。なお、使用す
る有機溶媒は含水量が１重量％未満のものまたは無水の
ものを用いるのが好ましい。As the DMDC used when preparing a solution of DMDC in an organic solvent, any of conventionally known compounds of dihydrate crystal and amorphous anhydrous can be used. As the organic solvent for dissolving the dihydrate crystal or the amorphous anhydride, a single solvent selected from the group consisting of alcohol (methanol, ethanol, propanol, etc.), dioxane and acetonitrile, or a mixture of two or more thereof is used. Mixed solvents can be used. The organic solvent used preferably has a water content of less than 1% by weight or is anhydrous.
【００２０】ＤＭＤＣの有機溶媒溶液は、ＤＭＤＣの二
水和物結晶または無定形無水物に約３〜３０倍重量の有
機溶媒を加え、５０〜１００℃に加温撹拌することによ
り調製することができる。A solution of DMDC in an organic solvent can be prepared by adding about 3 to 30 times by weight of an organic solvent to DMDC dihydrate crystals or amorphous anhydride and heating and stirring at 50 to 100 ° C. it can.
【００２１】ＤＭＤＣの有機溶媒溶液から本発明化合物
を得るには、該有機溶媒溶液を徐々に冷却して晶析させ
るか、溶解度の低い別の有機溶媒を加えて晶析させれば
よい。ここで、別の有機溶媒としては、上記有機溶媒と
同じものを例示することができ、ＤＭＤＣの有機溶媒溶
液を調製する際に使用したものとは別のものを使用すれ
ばよい。このようにして晶析させた結晶を濾取した後、
必要に応じて乾燥処理（加熱乾燥、通風乾燥または減圧
乾燥）を施し、本発明化合物とする。To obtain the compound of the present invention from a solution of DMDC in an organic solvent, the organic solvent solution may be gradually cooled for crystallization, or another organic solvent having a low solubility may be added for crystallization. Here, as the other organic solvent, the same one as the above organic solvent can be exemplified, and a different one from the one used when preparing the organic solvent solution of DMDC may be used. After filtering the crystal thus crystallized,
If necessary, drying treatment (heating drying, ventilation drying or reduced pressure drying) is performed to obtain the compound of the present invention.
【００２２】[0022]
【実施例】以下、実施例を示し、本発明をより具体的に
説明する。EXAMPLES Hereinafter, the present invention will be described more specifically by showing examples.
【００２３】実施例１ ＤＭＤＣの二水和物結晶５ｇにメタノール５ｍｌを加え
て加温溶解後、エタノール１０ｍｌを加えて晶析させ、
冷却後、濾取、乾燥して無水物結晶４．３７ｇを得た。 元素分析：測定値（％） Ｃ；５０．０３，Ｈ；５．５
０，Ｎ；１７．４３ 理論値（％） Ｃ；５０．２１，Ｈ；５．４８，Ｎ；１
７．５６ 旋光度〔α〕20 D ：−１４０．０（水溶液中） 赤外吸収スペクトル（ＫＢｒ法）：３２２８，１６５
５，１６１０，１５０４，１２８９，１０７０，１０３
８，７８４（ｃｍ-1）Example 1 To 5 g of DMDC dihydrate crystals, 5 ml of methanol was added and dissolved by heating, and then 10 ml of ethanol was added for crystallization,
After cooling, the crystals were collected by filtration and dried to obtain 4.37 g of anhydrous crystals. Elemental analysis: measured value (%) C; 50.03, H; 5.5
0, N; 17.43 theoretical value (%) C; 50.21, H; 5.48, N; 1
7.56 Optical rotation [α] 20 D : -140.0 (in aqueous solution) Infrared absorption spectrum (KBr method): 3228, 165
5,1610,1504,1289,1070,103
8,784 (cm -1 )
【００２４】実施例２ 二水和物結晶５ｇにメタノール１０ｍｌを加えて加温溶
解後、徐々に冷却して晶析させ、濾取、乾燥して無水物
結晶３．１９ｇを得た。さらに、この無水物結晶を微粉
砕器に供し、粒径が０．１〜１０μｍの微粉砕化された
無水物結晶を得た。Example 2 To 5 g of dihydrate crystals, 10 ml of methanol was added and dissolved by heating, followed by gradual cooling for crystallization, filtration and drying to obtain 3.19 g of anhydrous crystals. Further, this anhydrous crystal was subjected to a fine pulverizer to obtain a finely pulverized anhydrous crystal having a particle size of 0.1 to 10 μm.
【００２５】実施例３ 二水和物結晶５ｇにエタノール２０ｍｌを加えて加温溶
解後、徐々に冷却して晶析させ、濾取、乾燥して無水物
結晶４．２０ｇを得た。Example 3 20 ml of ethanol was added to 5 g of dihydrate crystals, dissolved by heating, gradually cooled to cause crystallization, filtered and dried to obtain 4.20 g of anhydrous crystals.
【００２６】実施例４ 二水和物結晶５ｇに１−プロパノール３０ｍｌを加えて
加熱溶解した後、徐々に冷却して晶析させ、濾取、乾燥
して無水物結晶４．２２ｇを得た。Example 4 To 5 g of dihydrate crystals, 30 ml of 1-propanol was added and dissolved by heating, then gradually cooled to cause crystallization, filtered and dried to obtain 4.22 g of anhydrous crystals.
【００２７】実施例５ 二水和物結晶５ｇに２−プロパノール３０ｍｌを加えて
加熱溶解した後、徐々に冷却して晶析させ、濾取、乾燥
して無水物結晶４．３９ｇを得た。Example 5 To 5 g of dihydrate crystals, 30 ml of 2-propanol was added and dissolved by heating, then gradually cooled to cause crystallization, filtered and dried to obtain 4.39 g of anhydrous crystals.
【００２８】実験例 本発明の無水物結晶（実施例１を使用）と、従来公知の
無定形無水物、二水和物結晶に対して、前記の方法に従
って水分含量、融点を測定し、示差走査熱量分析、粉末
Ｘ線回折、微粉砕試験、吸湿試験を行い、その結果を表
３に示した。Experimental Example The water content and melting point of the anhydrous crystal of the present invention (using Example 1) and the conventionally known amorphous anhydrous and dihydrate crystals were measured according to the above-mentioned method to give a difference. Scanning calorimetric analysis, powder X-ray diffraction, fine pulverization test and moisture absorption test were conducted, and the results are shown in Table 3.
【００２９】[0029]
【表３】 [Table 3]
【００３０】[0030]
【発明の効果】本発明化合物は、従来公知のＤＭＤＣの
二水和物結晶および無定形無水物とは物理化学的性質の
点で大きく相違し、全く新規な化合物である。しかも、
本発明化合物は、二水和物結晶および無定形無水物にな
い特性を有し、物理的な粉砕処理に対して安定で微粉砕
化が可能であるため、経口投与製剤のための医薬品原体
として有用である。INDUSTRIAL APPLICABILITY The compound of the present invention is a novel compound, which is largely different from the conventionally known DMDC dihydrate crystal and amorphous anhydride in the physicochemical properties. Moreover,
INDUSTRIAL APPLICABILITY The compound of the present invention has characteristics not found in dihydrate crystals and amorphous anhydrides, is stable against physical grinding treatment, and can be finely pulverized. Therefore, it is a drug substance for oral administration. Is useful as
【図１】本発明化合物であるＤＭＤＣの無水物結晶の示
差走査熱量分析曲線を示したものである。図面中、横軸
は温度を示し、縦軸は回折の示差走査熱量を示す。FIG. 1 shows a differential scanning calorimetry curve of anhydrous crystals of DMDC, which is a compound of the present invention. In the drawing, the horizontal axis represents temperature and the vertical axis represents the differential scanning calorific value of diffraction.
【図２】公知のＤＭＤＣの無定形無水物の示差走査熱量
分析曲線を示したものである。FIG. 2 is a graph showing a differential scanning calorimetry curve of a known anhydrous anhydrous DMDC.
【図３】公知のＤＭＤＣの二水和物結晶の示差走査熱量
分析曲線を示したものである。FIG. 3 shows a differential scanning calorimetry curve of known DMDC dihydrate crystals.
【図４】本発明化合物であるＤＭＤＣの無水物結晶の粉
末Ｘ線回折スペクトルを示したものである。図面中、横
軸は回折角度を示し、縦軸は回折の相対強度を示す。FIG. 4 shows a powder X-ray diffraction spectrum of anhydrous crystals of DMDC, which is a compound of the present invention. In the drawing, the horizontal axis represents the diffraction angle and the vertical axis represents the relative intensity of diffraction.
【図５】公知のＤＭＤＣの無定形無水物の粉末Ｘ線回折
スペクトルを示したものである。FIG. 5 shows a powder X-ray diffraction spectrum of a known amorphous anhydrous form of DMDC.
【図６】公知のＤＭＤＣの二水和物結晶の粉末Ｘ線回折
スペクトルを示したものである。FIG. 6 shows a powder X-ray diffraction spectrum of known DMDC dihydrate crystals.
Claims (6)
ジン無水物結晶。1. An anhydrous crystal of 2'-deoxy-2'-methylidene cytidine.
求項１記載の無水物結晶。2. The anhydrous crystal according to claim 1, which has a water content of 0.2% by weight or less.
査熱量分析で１９４〜１９８℃に吸熱ピークを示す、請
求項１記載の無水物結晶。3. The anhydrous crystal according to claim 1, which has a melting point of 180 to 184 ° C. and shows an endothermic peak at 194 to 198 ° C. by differential scanning calorimetry.
ピークを示す、請求項１記載の無水物結晶。 回折角２θ（°）：１１．２，１５．６，１８．５，１
９．０，２１．２，２２．５，２５．３および２７．２4. The anhydrous crystal according to claim 1, which shows major diffraction peaks at the following diffraction angles in powder X-ray diffraction. Diffraction angle 2θ (°): 11.2, 15.6, 18.5, 1
9.0, 21.2, 22.5, 25.3 and 27.2
メチリデンシチジン無水物結晶を微粉末化して得られ
る、粒径が０．１〜１０μｍの２’−デオキシ−２’−
メチリデンシチジン無水物結晶。5. The 2'-deoxy-2'- according to claim 1.
2′-deoxy-2′- having a particle size of 0.1 to 10 μm, which is obtained by pulverizing anhydrous methylidene cytidine crystals.
Methylidene cytidine anhydrous crystals.
ジンの有機溶媒溶液から２’−デオキシ−２’−メチリ
デンシチジンを晶析させることを特徴とする、２’−デ
オキシ−２’−メチリデンシチジン無水物結晶の製造
法。6. A 2'-deoxy-2'-methylidene cytidine is crystallized from a solution of 2'-deoxy-2'-methylidene cytidine in an organic solvent. Method for producing anhydrous methylidene cytidine crystals.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04334757A JP3077925B2 (en) | 1992-12-15 | 1992-12-15 | 2'-Deoxy-2'-methylidene cytidine anhydride crystals and method for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04334757A JP3077925B2 (en) | 1992-12-15 | 1992-12-15 | 2'-Deoxy-2'-methylidene cytidine anhydride crystals and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06179692A true JPH06179692A (en) | 1994-06-28 |
| JP3077925B2 JP3077925B2 (en) | 2000-08-21 |
Family
ID=18280893
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP04334757A Expired - Lifetime JP3077925B2 (en) | 1992-12-15 | 1992-12-15 | 2'-Deoxy-2'-methylidene cytidine anhydride crystals and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3077925B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001300293A (en) * | 2000-04-25 | 2001-10-30 | Nipro Corp | Method for manufacturing inorganic or organic anhydride |
| JP2003503508A (en) * | 1999-07-02 | 2003-01-28 | アストラゼネカ アクチボラグ | Substantial crystalline form of melagatran |
-
1992
- 1992-12-15 JP JP04334757A patent/JP3077925B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003503508A (en) * | 1999-07-02 | 2003-01-28 | アストラゼネカ アクチボラグ | Substantial crystalline form of melagatran |
| JP2001300293A (en) * | 2000-04-25 | 2001-10-30 | Nipro Corp | Method for manufacturing inorganic or organic anhydride |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3077925B2 (en) | 2000-08-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100207802B1 (en) | N- [4(5-cyclopentyloxycarbonyl) amino-1-methylindol-3-yl-methyl]-3-methoxybenzoyl]-2-methylbenzenesulfoneamide and the process for the preparation thereof | |
| TWI423968B (en) | Polymorphic forms of a macrocyclic inhibitor of hcv | |
| PT1296951E (en) | 5-chloro-3-(4-methanesulfonylphenyl)-6`-methyl- [2,3`] bipyridinyl in pure crystalline form and process for synthesis | |
| JP3726291B2 (en) | Benzoxazine compound having stable crystal structure and process for producing the same | |
| AU2020399168A1 (en) | Crystalline form of a 7H-benzo[7]annulene-2-carboxylic acid derivative | |
| TWI341731B (en) | Process of lyophilization for the preparation of piroxicam: β-cyclodextrin inclusion compound | |
| Athiyah et al. | Crystal engineering of quercetin by liquid assisted grinding method | |
| TW201829420A (en) | New solid forms of [(1s)-1-[(2s,4r,5r)-5-(5-amino-2-oxo-thiazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-yl]propyl] acetate | |
| JP2012521417A (en) | A novel crystalline form of adefovir dipivoxil and process for its production | |
| JPH06179692A (en) | 2'-deoxy-2'-methylidenecytidine anhydride crystal and its production | |
| EP4313945A1 (en) | Crastalline hydrobromide salt of 5-meo-dmt | |
| JP4015954B2 (en) | Suplatast tosilate crystal | |
| EP3283483A1 (en) | Crystalline eliglustat hydrochloride | |
| DE20320528U1 (en) | New crystal forms of ondansetron and medicines that contain the new forms | |
| JPH11513402A (en) | A new crystal form of morphine-6-glucuronide | |
| KR101589910B1 (en) | Process for Preparation and Conversion of Taltirelin Crystalline Form | |
| JPH04295485A (en) | Cephalosporin hydrate crystal for oral administration | |
| JP2005515987A (en) | Roziglitazone edicylate its use as an antidiabetic agent | |
| JP2707012B2 (en) | Crystal polymorph of N-tert-butyl-1-methyl-3,3-diphenylpropylamine hydrochloride and method for producing the same | |
| JP2006151976A (en) | Adapalene polymorphic form | |
| WO2021259316A1 (en) | Crystalline form of compound | |
| TWI825076B (en) | Process for the preparation of polymorph form b of treprostinil diethanolamine salt | |
| WO2022009815A1 (en) | Succinate of octahydrothienoquinoline compound, and crystals thereof | |
| HU210879A9 (en) | Pharmaceutical agents | |
| JP2753910B2 (en) | Crystal polymorph of N-tert-butyl-1-methyl-3,3-diphenylpropylamine hydrochloride and method for producing the same |