JPH01242582A - Production of type i crystal of quinolone-carboxylic acid compound - Google Patents
Production of type i crystal of quinolone-carboxylic acid compoundInfo
- Publication number
- JPH01242582A JPH01242582A JP6580588A JP6580588A JPH01242582A JP H01242582 A JPH01242582 A JP H01242582A JP 6580588 A JP6580588 A JP 6580588A JP 6580588 A JP6580588 A JP 6580588A JP H01242582 A JPH01242582 A JP H01242582A
- Authority
- JP
- Japan
- Prior art keywords
- crystal
- type
- crystals
- formula
- carboxylic acid
- 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
- 239000013078 crystal Substances 0.000 title claims abstract description 99
- -1 quinolone-carboxylic acid compound Chemical class 0.000 title claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000010438 heat treatment Methods 0.000 claims abstract description 5
- 238000002441 X-ray diffraction Methods 0.000 claims abstract description 4
- 230000001376 precipitating effect Effects 0.000 claims abstract description 3
- 239000000126 substance Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 11
- 238000009472 formulation Methods 0.000 abstract description 5
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 230000005855 radiation Effects 0.000 abstract 1
- 238000010792 warming Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 14
- 238000001914 filtration Methods 0.000 description 8
- 238000000634 powder X-ray diffraction Methods 0.000 description 7
- 230000007704 transition Effects 0.000 description 7
- 239000000843 powder Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000005260 alpha ray Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010981 drying operation Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
・ の１
本発明は合成抗菌剤であるキノロンカルボン酸化合物工
型結晶の製造法に関する。更に詳しくは［化学名：（±
）−１−エチル−６，８−ジフルオロ−１，４−ジヒド
ロ−７−（３−メチル−１−ピペラジニル）−４−オキ
ソ−３−キノリンカルボン酸塩酸塩］
で示される合成抗菌剤の結晶形の安定性に優れたキノロ
ンカルボン酸化合物Ｉ型結晶の製造法に関する。DETAILED DESCRIPTION OF THE INVENTION (1) The present invention relates to a method for producing engineered crystals of a quinolone carboxylic acid compound, which is a synthetic antibacterial agent. For more details [Chemical name: (±
)-1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic hydrochloride] This invention relates to a method for producing a type I crystal of a quinolone carboxylic acid compound having excellent shape stability.
従迷４ｕ石１
本発明の式（Ｉ）で示される化合物は特公昭６２−５６
１５１号に開示されている公知化合物である。しかしな
がら、この化合物に関する結晶多形については全く知ら
れていない。Jōmei 4u stone 1 The compound represented by the formula (I) of the present invention is
It is a known compound disclosed in No. 151. However, nothing is known about the crystal polymorphism of this compound.
Ｉｌ ｆ ″ −と
本発明者らは、式（Ｉ）で示される化合物の結晶多形に
ついて鋭意研究した結果、晶析条件の変化により結晶多
形が存在することを見い出すと共に、それらの中で結晶
形の安定性に最も優れ製剤化にも有用なＩ型結晶を見い
出し、本発明を完成したものである。As a result of intensive research on the crystal polymorphism of the compound represented by formula (I), the present inventors discovered that crystal polymorphism exists due to changes in crystallization conditions, and among them, The present invention was completed by discovering type I crystals, which have the best crystal stability and are useful for formulation.
、 −の−
式（Ｉ）で示される化合物の一般的な製造法としては、
特公昭６２−５６１５１号により、１−エチル−６，７
，８−）リフルオロ−１，４−ジヒドロ−４−オキソ−
３−キノリンカルボン酸と２−メチルピペラジンを常法
に従って反応させ、式（Ｉ）で示される化合物の塩基を
得、次いでこれを塩酸塩とした後、当該塩酸塩を水から
再結晶して製造する方法が知られている。, - of - As a general method for producing the compound represented by formula (I),
According to Special Publication No. 62-56151, 1-ethyl-6,7
,8-)lifluoro-1,4-dihydro-4-oxo-
3-quinolinecarboxylic acid and 2-methylpiperazine are reacted according to a conventional method to obtain a base of the compound represented by formula (I), which is then converted into a hydrochloride salt, and then the hydrochloride salt is recrystallized from water to produce it. There are known ways to do this.
本発明者らは、水からの再結晶時の多形の生成について
鋭意検討した結果、結晶多形には、Ｉ型（無水物）、■
型（２水和物）及び■型（■型の脱水物である無水物）
の３種が存在し、いずれも粉末Ｘ線回折図は異なった回
折ピークを示すことを見い出した。As a result of intensive studies on the formation of polymorphs during recrystallization from water, the present inventors found that the crystal polymorphs include type I (anhydride), type I (anhydride),
Type (dihydrate) and ■type (anhydrous which is a dehydrated product of ■type)
It has been found that there are three types, all of which exhibit different diffraction peaks in their powder X-ray diffractograms.
式（Ｉ）で示される化合物の製剤化に関する安定性を検
討する為、これらの多形の物理的性質及び結晶形の転移
について調べた結果、■型が安定性に最も優れ製剤化に
有用な結晶形であることを発見した。In order to examine the stability of the compound represented by formula (I) in formulation, we investigated the physical properties of these polymorphs and the transformation of crystal forms, and found that type Ⅰ has the highest stability and is useful for formulation. It was discovered that it is in crystalline form.
即ち、■型は極めて安定な結晶形で転移は認められなか
ったが、■型及び■型は室温で容易に他の結晶形に転移
することがわかった。That is, the ■-form was an extremely stable crystal form and no transition was observed, but it was found that the ■-form and ■-form easily transformed into other crystal forms at room temperature.
又、■型から他の結晶形へ転移する場合、あるいは■型
が■型へ転移する場合、結晶水の脱吸着がおこり含水量
が一定となりにくいこともわかった。この結晶形の転移
及び含水量の不安定性は製剤化上極めて問題となる点で
ある。It has also been found that when the ■-form transitions to another crystal form, or when the ■-form transitions to the ■-form, desorption of crystal water occurs, making it difficult for the water content to become constant. This transition of crystal form and instability of water content are extremely problematic in formulation.
本発明者らは■型結晶を効率よく確実に製造することを
目的として鋭意研究を重ねた結果、再結晶時の晶析条件
をコントロールすることにより、Ｉ型結晶のみを製造す
ることに成功した。As a result of extensive research aimed at efficiently and reliably producing type I crystals, the inventors succeeded in producing only type I crystals by controlling the crystallization conditions during recrystallization. .
本発明に係るＩ型結晶の製造方法によれば、まず、式（
Ｉ）で示される化合物を水に加熱溶解せしめ、４０″以
上の温度で結晶を析出させ、好ましくは４０″以上の温
度でＩ型結晶の種晶を添加することにより、もしくは４
０＠以上の温度で工型結晶の種晶及びエタノールを添加
することにより、他の結晶形の混在しないＩ型結晶のみ
を収率よく得ることができる。According to the method for manufacturing a type I crystal according to the present invention, first, the formula (
By heating and dissolving the compound represented by I) in water and precipitating crystals at a temperature of 40" or higher, preferably by adding type I crystal seed crystals at a temperature of 40" or higher, or
By adding seed crystals of engineering type crystals and ethanol at a temperature of 0@ or higher, only type I crystals without other crystal forms can be obtained in good yield.
本発明の方法において、結晶を析出させる温度は極めて
重要であって、その析出温度は４０″以上とすることが
必要である。析出温度が４０’より低い場合、析出する
結晶はＩ型、■型の混合物となり、その混合比も不規則
で乾燥後に得られる結晶形は一定せず、目的とするＩ型
のみが得られない。もちろん再結晶溶媒への溶解ロスを
抑えるため、４０″以上の温度で結晶析出が実質的に終
了した後、更に低い温度に冷却し、ろ取することを何ら
制限するものではない。また、再結晶溶媒は水単独であ
ってもよいが、水にエタノールを混合することにより、
水本来の溶解度より溶解度を低下せしめること、あるい
はろ過操作、乾燥操作を容易にすることができ、その結
果、Ｉ型結晶のみを収率よく得ることができる。本発明
に係るＩ型結晶はＣｕ−にα線のＸ線による粉末Ｘ線回
折測定による回折角２θ＝６．１°に鋭い回折ピークを
示し、２θ＝４〜５°に回折ピークを認めない結晶構造
を有するものである。In the method of the present invention, the temperature at which the crystals are precipitated is extremely important, and it is necessary to set the precipitation temperature to 40' or higher.If the precipitation temperature is lower than 40', the precipitated crystals are type I, The mixture ratio is irregular, and the crystal form obtained after drying is not constant, making it impossible to obtain only the desired type I. Of course, in order to suppress dissolution loss in the recrystallization solvent, There is no restriction at all on cooling to a lower temperature and filtering after crystal precipitation has substantially completed at that temperature. Also, the recrystallization solvent may be water alone, but by mixing ethanol with water,
The solubility can be lowered from the original solubility in water, or the filtration operation and drying operation can be made easier, and as a result, only type I crystals can be obtained in good yield. The type I crystal according to the present invention shows a sharp diffraction peak at a diffraction angle of 2θ = 6.1° when measured by powder X-ray diffraction using α-ray X-rays on Cu-, and no diffraction peak is observed at 2θ = 4 to 5°. It has a crystal structure.
次にＩ型、■型及び■型結晶の物理的性質と結晶形の転
移について調べた実験結果について説明する。Next, the results of experiments investigating the physical properties of type I, type ■, and type ■ crystals and transitions of crystal forms will be explained.
なお、実験に用いた各結晶形は以下の方法により製造し
た。Note that each crystal form used in the experiment was manufactured by the following method.
Ｉ型結晶：式（Ｉ）で示される化合物１ｇを水１５１に
加熱溶解し熱時ろ過後、６０″でＩ型結晶の種晶を添加
し、４０’ まで冷却した時点で、結晶がほぼ析出した
ことを目視で確認した後、室温で一昼夜撹拌した。次に
析出した結晶をろ取し、６０°で２４時間乾燥し、Ｉ型
結晶とした。Type I crystal: 1 g of the compound represented by the formula (I) was heated and dissolved in 151 kg of water, and after hot filtration, seed crystals of type I crystal were added at 60'', and when cooled to 40', almost the crystals were precipitated. After visually confirming this, the mixture was stirred at room temperature all day and night.Then, the precipitated crystals were collected by filtration and dried at 60° for 24 hours to form type I crystals.
■型結晶二式（Ｉ）で示される化合物１ｇを水３０ｍ１
に加熱溶解し熱時ろ過後、水冷下４時間放置した。次に
析出した結晶をろ取し、室温で２日間乾燥し、■型結晶
とした。■ Type crystal 2 1 g of the compound represented by formula (I) was added to 30 ml of water.
After heating to dissolve and filter while hot, the mixture was left to stand for 4 hours under water cooling. Next, the precipitated crystals were collected by filtration and dried at room temperature for 2 days to form ■-type crystals.
■型結晶：■型結晶を６０″で３時間通気乾燥し、ｍ型
結晶とした。■-type crystal: ■-type crystal was air-dried at 60'' for 3 hours to obtain m-type crystal.
（＋）元素分析値及び水分 各結晶形の元素分析値及び水分を第１表に示す。(+) Elemental analysis value and moisture content Table 1 shows the elemental analysis values and water content of each crystal form.
Ｉ型及びｍ型は無水物で■型は２分子の結晶水を含んで
いた。Types I and M were anhydrous, and type ■ contained two molecules of water of crystallization.
（２ン粉末Ｘ線回折図
粉末Ｘ線回折装置（理学電機製、Ｃｕ−にα線使用）を
用いて測定した式（Ｉ）で示される化合物のＩ型、■型
及びｍ型結晶の粉末Ｘ線回折図を第１．第２及び第３図
に示す。図がら明らがなように■型は回折角２θ＝８．
１，８．１，１１゜８．１４．３．１９．４”に、■型
は２θ＝４゜４．８．８．１２．８，１４．４，１７．
６”に、ｍ型は２θ＝４．８．９．４，１１．６，１３
゜２．１４．４”に回折ピークを示し、特にそれぞれ６
．１°、４．４°、４．８°の特異的な回折ピークによ
り結晶形が確認できる。(2-type powder X-ray diffraction diagram Powder of type I, type II, and type m crystals of the compound represented by formula (I) measured using a powder X-ray diffractometer (manufactured by Rigaku, using α rays for Cu-) The X-ray diffraction diagrams are shown in Figures 1, 2, and 3.As is not clear from the figures, the ■ type has a diffraction angle of 2θ = 8.
1, 8.1, 11° 8.14.3.19.4", ■ type is 2θ = 4° 4.8.8.12.8, 14.4, 17.
6”, m type has 2θ=4.8.9.4, 11.6, 13
It shows diffraction peaks at ゜2.14.4'', especially at 6.
．． The crystal form can be confirmed by specific diffraction peaks at 1°, 4.4°, and 4.8°.
、（３）溶解度 各結晶形の３７°での溶解度を第２表に示す。, (3) Solubility The solubility of each crystalline form at 37° is shown in Table 2.
■型及びｍ型は１型に比べ、約２．５倍の溶解度を示し
た。Type ① and Type m showed approximately 2.5 times higher solubility than Type 1.
第２表 各結晶形の溶解度
（４）結晶形の転移
各結晶形を２５’７５％ＲＨ及び４０°７５％ＲＨに３
０日間放置し、放置後の結晶形を粉末Ｘ線回折測定によ
り調べた結果を第３表に示す。■型に結晶形の変化は認
められなかったが、■型及び■型はＩ型及び■型の混合
物に転移していた。Table 2 Solubility of each crystal form (4) Transition of crystal form Each crystal form at 25°75%RH and 40°75%RH3
Table 3 shows the results of examining the crystal form by powder X-ray diffraction measurement after the sample was allowed to stand for 0 days. No change in crystal form was observed in type (2), but type (2) and type (2) were transformed into a mixture of type I and type (2).
第３表 湿度による結晶形の転移 以下に実施例を挙げて本発明を更に具体的に説明する。Table 3: Transition of crystal form due to humidity The present invention will be explained in more detail with reference to Examples below.
実施例１
式（Ｉ）で示される化合物２０ｇを水３００１に加熱溶
解し、ろ過する。ろ液を撹拌下４０°まで冷却し、更に
同温度にて２時間撹拌して結晶がほぼ析出したことを目
視で確認した後、更に２５゜まで冷却した。得られた結
晶をろ取し、６０６で２４時間乾燥したところ、白色結
晶１５ｇを得た。Example 1 20 g of the compound represented by formula (I) is heated and dissolved in water 3001 and filtered. The filtrate was cooled to 40° with stirring, and further stirred at the same temperature for 2 hours to visually confirm that most of the crystals had precipitated, and then further cooled to 25°. The obtained crystals were collected by filtration and dried at 606 for 24 hours to obtain 15 g of white crystals.
この白色結晶のＣｕ−にα線の粉末Ｘ線回折測定を行な
ったところ、回折角２θ＝Ｅ３． １’に鋭い回折ピー
クを示したが、２θ＝４〜５°に回折ピークは認めなか
った。この白色結晶はＩ型結晶であった。When α-ray powder X-ray diffraction measurement was performed on this white crystal Cu-, the diffraction angle 2θ=E3. A sharp diffraction peak was observed at 1', but no diffraction peak was observed at 2θ=4 to 5°. This white crystal was a type I crystal.
実施例２
式（Ｉ）で示される化合物２０ｇを水３００１に加熱溶
解し、ろ過する。ろ液を撹拌下、冷却を開始し、６０″
でＩ型結晶を種晶として投入する。Example 2 20 g of the compound represented by formula (I) is heated and dissolved in water 3001 and filtered. Start cooling the filtrate while stirring, and cool to 60"
Type I crystal is introduced as a seed crystal.
その後４０°まで冷却した時点で、結晶がほぼ析出した
ことを目視で確認した後、更に２５″まで冷却した。得
られた結晶をろ取し、６０″で２４時間乾燥したところ
白色結晶１５ｇを得た。この白色結晶は■型結晶であっ
た。After cooling to 40 degrees, it was visually confirmed that most of the crystals had precipitated, and the temperature was further cooled to 25". The obtained crystals were filtered and dried at 60" for 24 hours, yielding 15 g of white crystals. Obtained. This white crystal was a ■-type crystal.
実施例３
式（Ｉ）で示される化合物２０ｇを水３００１に加熱溶
解し、ろ過する。ろ液を撹拌下、冷却を開始し、６０″
でＩ型結晶を種晶として投入する。Example 3 20 g of the compound represented by formula (I) is heated and dissolved in water 3001 and filtered. Start cooling the filtrate while stirring, and cool to 60"
Type I crystal is introduced as a seed crystal.
その後１／２量のエタノールを徐々に加えた後、約４０
’ まで冷却し、更に同温度にて２時間撹拌して結晶が
析出したことを目視で確認した後、２５゜まで冷却した
。得られた結晶をろ取し、６０″で１２時間乾燥したと
ころ、白色結晶１５ｇを得た。After that, after gradually adding 1/2 amount of ethanol, about 40
The mixture was cooled to 25° and further stirred at the same temperature for 2 hours, visually confirming that crystals had precipitated, and then cooled to 25°. The obtained crystals were collected by filtration and dried at 60" for 12 hours to obtain 15 g of white crystals.
本結晶は実施例１と同様Ｉ型結晶であった。This crystal was a type I crystal as in Example 1.
参考例
実施例１のろ液を室温まで冷却しその後２４時間放置し
た。得られた結晶をろ取し、６０６で２４時間乾燥した
ところ、白色結晶Ｌｏｇを得た。Reference Example The filtrate of Example 1 was cooled to room temperature and then left for 24 hours. The obtained crystals were collected by filtration and dried at 606 for 24 hours to obtain white crystals Log.
この白色結晶のＣｕ−にα線の粉末Ｘ線回折測定を行っ
たところ、回折角２θ＝４．８＠に鋭い回折ピークを認
めたが、２θ；６．１°にはわずかな回折ピークしか認
めなかった。When α-ray powder X-ray diffraction measurement was performed on this white crystal Cu-, a sharp diffraction peak was observed at a diffraction angle of 2θ = 4.8@, but only a slight diffraction peak was observed at 2θ; 6.1°. I didn't admit it.
この結晶をさらに約１週間室温に放置したところ、２０
＝４．４°に回折ピークが現われ経時的に大きくなった
。本結晶は多形の混合物であった。When this crystal was left at room temperature for about a week, 20
A diffraction peak appeared at =4.4° and became larger over time. This crystal was a mixture of polymorphs.
第１図は、粉末Ｘ線回折装置で測定したＩ型結晶の粉末
Ｘ線回折図を、第２図は、粉末Ｘ線回折装置で測定した
■型結晶の粉末Ｘ線回折図を、第３図は、粉末Ｘ線回折
装置で測定した■型結晶の粉末Ｘ線回折図を、それぞれ
表わす。
特許出願人 北陸製薬株式会社Figure 1 shows the powder X-ray diffraction pattern of type I crystal measured with a powder X-ray diffractometer, Figure 2 shows the powder The figures each represent a powder X-ray diffraction pattern of a ■-type crystal measured with a powder X-ray diffractometer. Patent applicant Hokuriku Pharmaceutical Co., Ltd.
Claims (3)
しめ、４０゜以上の温度で結晶を析出させることを特徴
とするＣｕ−Ｋα線のＸ線によるＸ線回折測定による回
折角２θ＝６．１゜に鋭い回折ピークを示し、２θ＝４
〜５゜に回折ピークを認めない結晶構造を有する前記式
で示されるキノロンカルボン酸化合物 I 型結晶の製造
法。(1) A Cu-Kα X-ray characterized by dissolving a quinolone carboxylic acid compound represented by the formula ▲ mathematical formula, chemical formula, table, etc. in water by heating and precipitating crystals at a temperature of 40° or higher. X-ray diffraction measurements showed a sharp diffraction peak at a diffraction angle of 2θ = 6.1°, and 2θ = 4
A method for producing a type I crystal of a quinolone carboxylic acid compound represented by the above formula, which has a crystal structure in which no diffraction peak is observed at an angle of ~5°.
の種晶を入れて結晶を析出させることを特徴とする特許
請求の範囲第１項記載の製造法。(2) The manufacturing method according to claim 1, characterized in that a seed crystal of type I crystal represented by the above formula is introduced at a temperature of 40° or more to precipitate the crystal.
の種晶及びエタノールを加えて、結晶を析出させること
を特徴とする特許請求の範囲第１項記載の製造法。(3) The manufacturing method according to claim 1, characterized in that the crystals are precipitated by adding seed crystals of type I crystals represented by the above formula and ethanol at a temperature of 40° or higher.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63065805A JP2676521B2 (en) | 1988-03-22 | 1988-03-22 | Method for producing quinolonecarboxylic acid compound type I crystal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63065805A JP2676521B2 (en) | 1988-03-22 | 1988-03-22 | Method for producing quinolonecarboxylic acid compound type I crystal |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01242582A true JPH01242582A (en) | 1989-09-27 |
| JP2676521B2 JP2676521B2 (en) | 1997-11-17 |
Family
ID=13297612
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63065805A Expired - Lifetime JP2676521B2 (en) | 1988-03-22 | 1988-03-22 | Method for producing quinolonecarboxylic acid compound type I crystal |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2676521B2 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0661974A4 (en) * | 1991-11-27 | 1994-08-29 | Sepracor Inc | Methods and compositions for treating infection using optically pure (r)-lomefloxacin. |
| EP0614364A1 (en) * | 1991-11-27 | 1994-09-14 | Sepracor, Inc. | Methods and compositions for treating infection using optically pure (s)-lomefloxacin |
| US5985893A (en) * | 1994-11-18 | 1999-11-16 | Pharmacia & Upjohn Company | Physically stable solid form of a fluoroquinolone |
| WO2000052010A1 (en) * | 1999-02-26 | 2000-09-08 | Bayer Aktiengesellschaft | Crystal modification d of 8-cyano-1-cyclopropyl-7- (1s, 6s- 2,8- diazabicyclo- [4.3.0] nonan-8-yl) -6-fluoro -1,4-dihydro -4-oxo -3-quinoline carboxylic acid |
| JP2002530407A (en) * | 1998-11-25 | 2002-09-17 | バイエル アクチェンゲゼルシャフト | 8-cyano-1-cyclopropyl-7- (1S, 6S-2,8-diazabicyclo [4.3.0] nonan-8-yl) -6-fluoro-1,4-dihydro-4-oxo-3 -Crystalline modification B of quinoline carboxylic acid |
| JP2002530406A (en) * | 1998-11-25 | 2002-09-17 | バイエル アクチェンゲゼルシャフト | 8-cyano-1-cyclopropyl-7- (1S, 6S-2,8-diazabicyclo [4.3.0] nonan-8-yl) -6-fluoro-1,4-dihydro-4-oxo-3 -Crystalline modification A of quinoline carboxylic acid |
| US6649762B1 (en) | 1999-02-26 | 2003-11-18 | Bayer Aktiengesellschaft | Crystal modification C of 8-cyano-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihyro-4-oxo-3-quinoline carboxylic |
-
1988
- 1988-03-22 JP JP63065805A patent/JP2676521B2/en not_active Expired - Lifetime
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0661974A4 (en) * | 1991-11-27 | 1994-08-29 | Sepracor Inc | Methods and compositions for treating infection using optically pure (r)-lomefloxacin. |
| EP0614364A1 (en) * | 1991-11-27 | 1994-09-14 | Sepracor, Inc. | Methods and compositions for treating infection using optically pure (s)-lomefloxacin |
| EP0614364A4 (en) * | 1991-11-27 | 1994-10-19 | Sepracor Inc | Methods and compositions for treating infection using optically pure (s)-lomefloxacin. |
| EP0661974A1 (en) * | 1991-11-27 | 1995-07-12 | Sepracor, Inc. | Methods and compositions for treating infection using optically pure (r)-lomefloxacin |
| US5985893A (en) * | 1994-11-18 | 1999-11-16 | Pharmacia & Upjohn Company | Physically stable solid form of a fluoroquinolone |
| JP2002530407A (en) * | 1998-11-25 | 2002-09-17 | バイエル アクチェンゲゼルシャフト | 8-cyano-1-cyclopropyl-7- (1S, 6S-2,8-diazabicyclo [4.3.0] nonan-8-yl) -6-fluoro-1,4-dihydro-4-oxo-3 -Crystalline modification B of quinoline carboxylic acid |
| JP2002530406A (en) * | 1998-11-25 | 2002-09-17 | バイエル アクチェンゲゼルシャフト | 8-cyano-1-cyclopropyl-7- (1S, 6S-2,8-diazabicyclo [4.3.0] nonan-8-yl) -6-fluoro-1,4-dihydro-4-oxo-3 -Crystalline modification A of quinoline carboxylic acid |
| JP2012236841A (en) * | 1998-11-25 | 2012-12-06 | Bayer Animal Health Gmbh | Crystal modification b of 8-cyano-1-cyclopropyl-7-(1s,6s-2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid |
| WO2000052010A1 (en) * | 1999-02-26 | 2000-09-08 | Bayer Aktiengesellschaft | Crystal modification d of 8-cyano-1-cyclopropyl-7- (1s, 6s- 2,8- diazabicyclo- [4.3.0] nonan-8-yl) -6-fluoro -1,4-dihydro -4-oxo -3-quinoline carboxylic acid |
| US6492391B1 (en) | 1999-02-26 | 2002-12-10 | Bayer Aktiengesellschaft | Crystal modification d of 8-cyano-1-cyclopropyl-7-(1s, 6s- 2,8-diazabicyclo-[4.3.0]nonan-8-yl)-6-fluoro-1,4- dihydro-4-oxo-3-quinolinecarboxylic acid |
| US6649762B1 (en) | 1999-02-26 | 2003-11-18 | Bayer Aktiengesellschaft | Crystal modification C of 8-cyano-1-cyclopropyl-7-(1S,6S-2,8-diazabicyclo-[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihyro-4-oxo-3-quinoline carboxylic |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2676521B2 (en) | 1997-11-17 |
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