[go: up one dir, main page]

CN106397402B - A kind of esomeprazole magnesium crystal compound and preparation method thereof - Google Patents

A kind of esomeprazole magnesium crystal compound and preparation method thereof Download PDF

Info

Publication number
CN106397402B
CN106397402B CN201610767662.0A CN201610767662A CN106397402B CN 106397402 B CN106397402 B CN 106397402B CN 201610767662 A CN201610767662 A CN 201610767662A CN 106397402 B CN106397402 B CN 106397402B
Authority
CN
China
Prior art keywords
esomeprazole magnesium
preparation
solution
mixed solvent
water
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.)
Active
Application number
CN201610767662.0A
Other languages
Chinese (zh)
Other versions
CN106397402A (en
Inventor
于德峰
杨磊祥
李桂国
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shandong Luoxin Pharmaceutical Group Co Ltd
Original Assignee
Shandong Luoxin Pharmaceutical Group Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shandong Luoxin Pharmaceutical Group Co Ltd filed Critical Shandong Luoxin Pharmaceutical Group Co Ltd
Priority to CN201610767662.0A priority Critical patent/CN106397402B/en
Publication of CN106397402A publication Critical patent/CN106397402A/en
Application granted granted Critical
Publication of CN106397402B publication Critical patent/CN106397402B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明属于医药技术领域。具体地说，本发明涉及埃索美拉唑镁晶型化合物。所述的埃索美拉唑镁化合物的结构式如下：所述的埃索美拉唑镁晶型化合物使用Cu‑Ka射线测量得到的X‑射线粉末衍射谱图如图1所示。本发明提供的埃索美拉唑镁是一种不同于现有技术的新晶型化合物，该新晶型化合物水溶性增大，采用本发明的埃索拉唑镁新晶型化合物制得的制剂较现有技术相比具有较好的生物利用度。

The invention belongs to the technical field of medicine. Specifically, the present invention relates to esomeprazole magnesium crystalline compounds. The structural formula of the described esomeprazole magnesium compound is as follows: The X-ray powder diffraction spectrum of the esomeprazole magnesium crystalline compound measured by Cu-Ka rays is shown in Figure 1. The esomeprazole magnesium provided by the present invention is a new crystal form compound different from the prior art, and the new crystal form compound has increased water solubility. The preparation has better bioavailability than the prior art.

Description

A kind of esomeprazole magnesium crystal-form compound and preparation method thereof
Technical field
The invention belongs to pharmaceutical technology fields, specifically, being related to a kind of esomeprazole magnesium crystalline compounds and its system Preparation Method.
Background technique
Esomeprazole magnesium is the S configuration of Omeprazole, is that a kind of novel antiulcer drug and proton pump inhibit, I.e. (S)-Omeprazole has better safety and curative effect, and the chiral proton pump for becoming the first listing in the whole world for 2001 inhibits Agent, magnesium salts form will not change configuration, be still S configuration, the entitled bis- (5- methoxyl group -2- (S)-((4- methoxyl group -3,5- of chemistry Dimethyl -2- pyridyl group) methyl)-sulfinyl) -1H- benzimidazole -1- base) magnesium salts, commercialized product is its trihydrate, Structural formula (I) is as follows:
WO98/54171 makes public for the first time the crystal form of Esomeprazole magnesium salt, later WO2006/003163,
WO2004/089935, WO2004/046134 also disclose a variety of crystalline substances of Esomeprazole magnesium salt and its hydrate Type.
However the dissolubility of the esomeprazole magnesium crystal for using the recrystallization method of the prior art to obtain in water is poor, it is raw Object availability is not high, so that the effect of drug administration is affected, the poor compliance for patient.
The crystal form of drug affects the exploitation of pharmaceutical preparation.Studies have shown that the same drug of different crystal forms is in solubility, molten Point, density, stability etc. may have significant difference, and then influence the stability, homogeneity, biological utilisation of drug Degree, efficacy and saferry.In recent years, pharmaceutical production, quality control and new drug is had become for the crystal form research of drug to grind Study carefully indispensable important component.In this regard, having been obtained a kind of different from existing skill present inventor has performed a large amount of research The esomeprazole magnesium crystal compound of art, and surprisingly find that the crystal compound can improve water through solubility test In dissolubility.
Summary of the invention
It is an object of the invention to provide a kind of esomeprazole magnesium crystal-form compound, which has stability height, water-soluble Good, the high feature of bioavilability of property.
Another object of the present invention, which also resides in, discloses the preparation method of esomeprazole magnesium crystal-form compound.
To achieve the purpose of the present invention, the present invention adopts the following technical scheme:
Esomeprazole magnesium crystal-form compound shown in a kind of formula (I), wherein
The X-ray powder diffraction spectrogram that the esomeprazole magnesium crystal-form compound is obtained using Cu-K alpha ray measurement As shown in Figure 1.
The present invention furthermore provides the preparation method of the esomeprazole magnesium crystal-form compound, and this method includes such as Lower step:
1) prepare solution A: the mixed solvent A of ether and acetonitrile is sterile filtered into crystallizing tank, cooling 5~10 DEG C after to With；
2) it prepares B solution: at room temperature, the mixed solvent B of water and ethyl alcohol being added in dissolving tank, add the drawing of Esso U.S. Azoles magnesium crude product, is added active carbon, stirring decoloration after dissolution, filtering is washed with water, collects filtrate and cleaning solution, obtain B solution；
3) B solution is added in solution, controls temperature to 10 DEG C~15 DEG C, the temperature is kept to be stirred 35min；
4) again by greenhouse cooling to 0 DEG C~5 DEG C, 10~15 turns/min of mixing speed is controlled, controls thermometer stirring speed 1~3h of growing the grain is spent, suction filtration obtains esomeprazole magnesium.
Preferably, the volume ratio of ether and acetonitrile is 2~6:1 in mixed solvent A described in step 1).
Preferably, the volume ratio of water and ethyl alcohol is 3~5:1 in mixed solvent B described in step 2)；The institute The mass volume ratio of the esomeprazole magnesium crude product and mixed solvent A, mixed solvent B stated is 1:20:2~4kg/L；The stirring Bleaching time is 20~30min.
Preferably, the mixing speed of stirring described in step 3) is 18~24 turns/min.
The present inventor passes through a large amount of repetition test, constantly changes method for crystallising and including solvent, anti-solvent, temperature etc. Crystallization condition, finally obtains a kind of novel crystal forms of esomeprazole magnesium, and the esomeprazole magnesium of the novel crystal forms has preferable steady It is qualitative, and esomeprazole magnesium compared with the prior art improves dissolubility in water.
Meanwhile the present invention has surprisingly found that under prescription and the identical situation of preparation method in pharmacodynamics test, uses The peak plasma concentrations of esomeprazole magnesium test film made from esomeprazole magnesium compound of the invention are higher than original and grind patent The crystal-form compound that the embodiment 1 of CN98805521.X is prepared to photo, improve product bioavilability.
Detailed description of the invention
Fig. 1 is the X-ray powder diffraction figure of esomeprazole magnesium crystal-form compound prepared by the embodiment of the present invention 1；
Fig. 2 is the thermogravimetric analysis map of esomeprazole magnesium crystal-form compound prepared by the embodiment of the present invention 1；
After Fig. 3 is for animal pharmacodynamics test single oral dose esomeprazole magnesium test film and to photo 20mg, it is averaged Drug-time curve figure.
Specific embodiment
The present invention can be further described by the following examples, however, invention of the invention and unlimited In the following examples, these embodiments are not limited the scope of the invention in any way.Those skilled in the art is in right Made certain changes and adjustment also are regarded as belonging to the scope of the present invention in the range of it is required that.
The preparation of 1 esomeprazole magnesium crystal-form compound of embodiment
1) prepare solution A: by the mixed solvent A of 500L ether and acetonitrile (wherein the volume ratio of ether and acetonitrile is 2:1) Aseptic filtration is stand-by after being cooled to 5 DEG C into crystallizing tank, as solution A；
2) prepare B solution: at room temperature, by the mixed solvent B of 50L water and ethyl alcohol (wherein the volume ratio of water and ethyl alcohol is 3: 1) it is added in dissolving tank, adds esomeprazole magnesium crude product 25kg, active carbon 0.38kg, stirring decoloration are added after dissolution 20min is sterile filtered, is washed with 10kg water for injection, collects filtrate and cleaning solution.Obtain B solution；
3) B solution is added in solution A, is cooled to 10 DEG C, keep the temperature, stirred with the mixing speed of 20 turns/min 35min；
4) 0 DEG C is cooled the temperature to again, controls 10 turns/min of mixing speed, controls temperature growing the grain 1h, is filtered, dry angstrom Rope magnesium draws azoles magnesium crystal-form compound.
Obtained esomeprazole magnesium is measured with powder x-ray diffraction measuring method, obtains X-ray powder diffraction collection As shown in Figure 1.
Using Perkin-Elmer company, U.S. PE Pyris Diamond TG thermogravimetric analyzer, table is tested in thermogravimetric analysis It is bright, as a result as shown in Fig. 2, crystal water content is 7.096wt%, contain 3 crystallizations water (theoretical value 7.045wt%) with theoretical value As a result within the error range.
The preparation of 2 esomeprazole magnesium crystal-form compound of embodiment
1) prepare solution A: by the mixed solvent A of 500L ether and acetonitrile (wherein the volume ratio of ether and acetonitrile is 2:1) Aseptic filtration is stand-by after being cooled to 10 DEG C into crystallizing tank, as solution A；
2) prepare B solution: at room temperature, by the mixed solvent B of 100L water and ethyl alcohol (wherein the volume ratio of water and ethyl alcohol is 3: 1) it is added in dissolving tank, adds esomeprazole magnesium crude product 25kg, active carbon 0.38kg, stirring decoloration are added after dissolution 30min is sterile filtered, is washed with 10kg water for injection, collects filtrate and cleaning solution.Obtain B solution；
3) B solution is added in solution A, is cooled to 10 DEG C, keep the temperature, stirred with the mixing speed of 20 turns/min 35min；
4) 5 DEG C are cooled the temperature to again, controls 10 turns/min of mixing speed, controls temperature growing the grain 1h, are filtered, dry angstrom Rope magnesium draws azoles magnesium crystal-form compound.
The X-ray powder diffraction collection that resulting esomeprazole magnesium crystal-form compound is obtained using Cu-K alpha ray measurement Consistent, the thermogravimetric obtained using Perkin-Elmer company, U.S. PE Pyris Diamond TG thermogravimetric analyzer with embodiment 1 It analyzes map and embodiment 1 is consistent.
The preparation of 3 esomeprazole magnesium crystal-form compound of embodiment
1) prepare solution A: by the mixed solvent A of 500L ether and acetonitrile (wherein the volume ratio of ether and acetonitrile is 6:1) Aseptic filtration is stand-by after being cooled to 5 DEG C into crystallizing tank, as solution A；
2) prepare B solution: at room temperature, by the mixed solvent B of 50L water and ethyl alcohol (wherein the volume ratio of water and ethyl alcohol is 5: 1) it is added in dissolving tank, adds esomeprazole magnesium crude product 25kg, active carbon 0.38kg, stirring decoloration are added after dissolution 20min is sterile filtered, is washed with 10kg water for injection, collects filtrate and cleaning solution.Obtain B solution；
3) B solution is added in solution A, is cooled to 15 DEG C, keep the temperature, stirred with the mixing speed of 20 turns/min 35min；
4) 0 DEG C is cooled the temperature to again, controls 15 turns/min of mixing speed, controls temperature growing the grain 3h, is filtered, dry angstrom Rope magnesium draws azoles magnesium crystal-form compound.
The X-ray powder diffraction collection that resulting esomeprazole magnesium crystal-form compound is obtained using Cu-K alpha ray measurement Consistent, the thermogravimetric obtained using Perkin-Elmer company, U.S. PE Pyris Diamond TG thermogravimetric analyzer with embodiment 1 It analyzes map and embodiment 1 is consistent.
The preparation of 4 esomeprazole magnesium crystal-form compound of embodiment
1) prepare solution A: by the mixed solvent A of 500L ether and acetonitrile (wherein the volume ratio of ether and acetonitrile is 6:1) Aseptic filtration is stand-by after being cooled to 10 DEG C into crystallizing tank, as solution A；
2) prepare B solution: at room temperature, by the mixed solvent B of 100L water and ethyl alcohol (wherein the volume ratio of water and ethyl alcohol is 5: 1) it is added in dissolving tank, adds esomeprazole magnesium crude product 25kg, active carbon 0.38kg, stirring decoloration are added after dissolution 30min is sterile filtered, is washed with 10kg water for injection, collects filtrate and cleaning solution.Obtain B solution；
3) B solution is added in solution A, is cooled to 15 DEG C, keep the temperature, stirred with the mixing speed of 20 turns/min 35min；
4) 5 DEG C are cooled the temperature to again, controls 15 turns/min of mixing speed, controls temperature growing the grain 3h, are filtered, dry angstrom Rope magnesium draws azoles magnesium crystal-form compound.
The X-ray powder diffraction collection that resulting esomeprazole magnesium crystal-form compound is obtained using Cu-K alpha ray measurement Consistent, the thermogravimetric obtained using Perkin-Elmer company, U.S. PE Pyris Diamond TG thermogravimetric analyzer with embodiment 1 It analyzes map and embodiment 1 is consistent.
Test example 1
Solubility test
The test example has investigated the esomeprazole magnesium of esomeprazole magnesium crystal-form compound and the prior art of the invention Dissolubility in water.
Sample number into spectrum is as follows:
Sample 1: esomeprazole magnesium crystal-form compound is made in the embodiment of the present invention 1；
Sample 2: esomeprazole magnesium crystal-form compound made from the embodiment of the present invention 3；
Sample 3: esomeprazole magnesium trihydrate made from the method according to the embodiment 1 of patent CN98805521.X；
Sample 4: esomeprazole magnesium trihydrate made from the method according to the embodiment 10 of patent CN 103509001A It is amorphous.
Solubility test method:
The solubility test of following several solvents has been done according to method as defined in Chinese Pharmacopoeia 2010 version two " note on the use ".
Method: weigh be ground into fine powder each sample it is appropriate (being accurate to ± 2.0%), the water of a certain amount of volume is added, 25 ± 2 DEG C shook 30 seconds every 5 minutes at room temperature, and observation dissolved situation in 30 minutes, the results are shown in Table 1.
1 solubility test result of table
As can be seen from the test results, compared with prior art, the present invention esomeprazole magnesium crystal form produced by the present invention The dissolubility of compound in water increases, suitable with amorphous products solubility.
Test example 2
Stability test
This experiment is according to 2010 editions second annex, Ⅺ Ⅹ C bulk pharmaceutical chemicals of Chinese Pharmacopoeia and drug preparation stability test direction Principle carries out, accelerated test condition: 40 DEG C ± 2 DEG C of temperature, relative humidity 75% ± 5%.Long term test condition: 25 DEG C of temperature ± 2 DEG C, relative humidity 60% ± 10%.Test result is shown in Table 2.
Table 2: stability test result
Test result shows that this product is placed 6 months under the conditions of 40 ± 2 DEG C of temperature, relative humidity 75% ± 5%, in temperature 25 DEG C ± 2 DEG C of degree, relative humidity 60% ± 10% are placed 12 months, and indices have no significant change, and it is good to illustrate that this product has Good stability.
Test example 3
Animal pharmacodynamics test: Beagle dog
Dosage and mode: the esomeprazole magnesium crystal-form compound (test film) that preparation method obtains in embodiment 1 Plain piece (to photo) is made in the crystal-form compound being prepared with the embodiment 1 of CN98805521.X, and dosage is respectively 20mg, be administered orally in the morning after animal fasting, and average drug-time curve is shown in Fig. 3.
From figure 3, it can be seen that after using the administration of test film made from esomeprazole crystal-form compound of the invention, blood medicine Concentration peak is significantly higher than reference substance blood concentration, shows that effective component bioavilability significantly improves.
Phase has also under equal conditions been carried out respectively to the esomeprazole magnesium crystal-form compound of other embodiments of the present invention Same test has and significantly improves with upper identical trend, i.e. effective component bioavilability.

Claims (7)

1.一种埃索美拉唑镁晶型化合物，其特征在于，所述的埃索美拉唑镁晶型化合物的结构式如下：1. an esomeprazole magnesium crystal compound, is characterized in that, the structural formula of described esomeprazole magnesium crystal compound is as follows: 所述的埃索美拉唑镁晶体化合物使用Cu-Kα射线测量得到的X-射线粉末衍射谱图如图1所示。The X-ray powder diffraction spectrum of the esomeprazole magnesium crystalline compound measured by Cu-Kα rays is shown in FIG. 1 . 2.一种权利要求1所述的埃索美拉唑镁晶型化合物的制备方法，其特征在于，所述的制备方法包括如下步骤：2. a preparation method of esomeprazole magnesium crystal compound according to claim 1, is characterized in that, described preparation method comprises the steps: 1)配制A溶液：将乙醚和乙腈的混合溶剂A无菌过滤至结晶罐中，降温5～10℃后待用；1) Preparation of solution A: Aseptically filter the mixed solvent A of ether and acetonitrile into a crystallizing tank, and cool it down by 5 to 10°C for later use; 2)配制B溶液：室温下，将水和乙醇的混合溶剂B加入到溶解罐中，再加入埃索美拉唑镁粗品，溶解后加入活性炭，搅拌脱色，过滤，用水洗涤，收集滤液和洗涤液，得B溶液；2) Preparation of B solution: at room temperature, add the mixed solvent B of water and ethanol into the dissolving tank, then add the crude esomeprazole magnesium, add activated carbon after dissolving, stir and decolorize, filter, wash with water, collect the filtrate and wash solution, get B solution; 3)将B溶液加至A溶液内，控制温度至10℃～15℃，保持该温度进行搅拌35min；3) Add solution B to solution A, control the temperature to 10°C to 15°C, and keep the temperature for stirring for 35 minutes; 4)再将温度降温至0℃～5℃，控制搅拌速度10～15转/min，控制该温度计搅拌速度养晶1～3h，抽滤得到埃索美拉唑镁。4) The temperature is then lowered to 0°C to 5°C, the stirring speed is controlled to 10 to 15 rpm, the stirring speed of the thermometer is controlled to grow crystals for 1 to 3 hours, and esomeprazole magnesium is obtained by suction filtration. 3.根据权利要求2所述的制备方法，其特征在于，步骤1)中所述的混合溶剂A中乙醚和乙腈的体积比为2～6:1。3. preparation method according to claim 2 is characterized in that, in the mixed solvent A described in step 1), the volume ratio of ether and acetonitrile is 2～6:1. 4.根据权利要求2所述的制备方法，其特征在于，步骤2)中所述的混合溶剂B中水和乙醇的体积比为3～5:1。4. The preparation method according to claim 2, wherein the volume ratio of water and ethanol in the mixed solvent B described in step 2) is 3 to 5:1. 5.根据权利要求2所述的制备方法，其特征在于，步骤2)中所述的埃索美拉唑镁粗品与混合溶剂A、混合溶剂B的质量体积比为1:20:2～4kg/L。5. preparation method according to claim 2 is characterized in that, the mass volume ratio of esomeprazole magnesium crude product described in step 2) and mixed solvent A, mixed solvent B is 1:20:2～4kg /L. 6.根据权利要求2所述的制备方法，其特征在于，步骤2)中所述搅拌脱色时间为20～30min。6 . The preparation method according to claim 2 , wherein the stirring and decolorizing time in step 2) is 20-30 min. 7 . 7.根据权利要求2所述的制备方法，其特征在于，步骤3)中所述搅拌的搅拌速度为18～24转/min。7 . The preparation method according to claim 2 , wherein the stirring speed of the stirring in step 3) is 18-24 rev/min. 8 .
CN201610767662.0A 2016-08-30 2016-08-30 A kind of esomeprazole magnesium crystal compound and preparation method thereof Active CN106397402B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610767662.0A CN106397402B (en) 2016-08-30 2016-08-30 A kind of esomeprazole magnesium crystal compound and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610767662.0A CN106397402B (en) 2016-08-30 2016-08-30 A kind of esomeprazole magnesium crystal compound and preparation method thereof

Publications (2)

Publication Number Publication Date
CN106397402A CN106397402A (en) 2017-02-15
CN106397402B true CN106397402B (en) 2019-05-03

Family

ID=58004001

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610767662.0A Active CN106397402B (en) 2016-08-30 2016-08-30 A kind of esomeprazole magnesium crystal compound and preparation method thereof

Country Status (1)

Country Link
CN (1) CN106397402B (en)

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1161351C (en) * 1997-05-30 2004-08-11 阿斯特拉公司 Novel form of S-omeprazole
WO2004089935A1 (en) * 2003-04-10 2004-10-21 Hetero Drugs Limitd Novel crystalline forms of s-omeprazole magnesium
WO2008149204A1 (en) * 2007-06-07 2008-12-11 Aurobindo Pharma Limited An improved process for preparing an optically active proton pump inhibitor
CN103509001A (en) * 2012-06-15 2014-01-15 石药集团中奇制药技术（石家庄）有限公司 Esomeprazole magnesium trihydrate and preparation method thereof
CN104356114A (en) * 2014-11-17 2015-02-18 江苏中邦制药有限公司 Preparation method of esomeprazole magnesium trihydrate
CN104447699A (en) * 2014-12-10 2015-03-25 哈药集团技术中心 Preparation method of esomeprazole magnesium trihydrate
CN104610227A (en) * 2015-01-08 2015-05-13 浙江亚太药业股份有限公司 High-pressure hydrothermal preparation method for esomeprazole magnesium polymorphic compound
CN105111188A (en) * 2015-08-19 2015-12-02 扬子江药业集团有限公司 Preparation method for esomeprazole magnesium trihydrate crystalline form
CN105418589A (en) * 2016-01-17 2016-03-23 青岛辰达生物科技有限公司 Preparation method of esomeprazole magnesium trihydrate for treating digestive system diseases

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040242642A1 (en) * 2002-11-18 2004-12-02 Dr. Reddy's Laboratories Limited Crystalline esomeprazole compounds and process for the preparation thereof

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1161351C (en) * 1997-05-30 2004-08-11 阿斯特拉公司 Novel form of S-omeprazole
WO2004089935A1 (en) * 2003-04-10 2004-10-21 Hetero Drugs Limitd Novel crystalline forms of s-omeprazole magnesium
WO2008149204A1 (en) * 2007-06-07 2008-12-11 Aurobindo Pharma Limited An improved process for preparing an optically active proton pump inhibitor
CN103509001A (en) * 2012-06-15 2014-01-15 石药集团中奇制药技术（石家庄）有限公司 Esomeprazole magnesium trihydrate and preparation method thereof
CN104356114A (en) * 2014-11-17 2015-02-18 江苏中邦制药有限公司 Preparation method of esomeprazole magnesium trihydrate
CN104447699A (en) * 2014-12-10 2015-03-25 哈药集团技术中心 Preparation method of esomeprazole magnesium trihydrate
CN104610227A (en) * 2015-01-08 2015-05-13 浙江亚太药业股份有限公司 High-pressure hydrothermal preparation method for esomeprazole magnesium polymorphic compound
CN105111188A (en) * 2015-08-19 2015-12-02 扬子江药业集团有限公司 Preparation method for esomeprazole magnesium trihydrate crystalline form
CN105418589A (en) * 2016-01-17 2016-03-23 青岛辰达生物科技有限公司 Preparation method of esomeprazole magnesium trihydrate for treating digestive system diseases

Also Published As

Publication number Publication date
CN106397402A (en) 2017-02-15

Similar Documents

Publication Publication Date Title
CA2999589C (en) Complex of angiotensin receptor antagonist and neutral endopeptidase inhibitor
JP6518352B2 (en) Amorphous form of pyrimidinylcyclopentane compounds which inhibit AKT, composition and method thereof
US20210260058A1 (en) Nilotinib Compositions with Enhanced Solubility
CN105753904A (en) Refining method for tedizolid phosphate
CN108383845B (en) Crystal form and amorphous form of Shengagliptin salt and its preparation method and use
CN102276630B (en) Cefminox sodium crystalline compound and composition powder injection thereof
WO2014036865A1 (en) Method for preparing fingolimod mucate and crystal thereof and application of fingolimod mucate and crystal thereof
CN114456140B (en) Eutectic crystal of icariin and theophylline
CN106397402B (en) A kind of esomeprazole magnesium crystal compound and preparation method thereof
CN103509001B (en) A kind of esomeprazole magnesium trihydrate and preparation method thereof
CN112538123B (en) Shugansu sodium crystal form M
CN113121419A (en) Acipimox-1, 2-di (4-pyridyl) ethylene eutectic crystal
CN104817523A (en) A drug ranitidine hydrochloride compound for treating stomach disease and preparation method thereof
CN114075169B (en) Osimertinib pharmaceutical co-crystal and preparation method thereof
CN114685434B (en) Acetinib and glutaric acid eutectic crystal
CN110078679B (en) A kind of lamotrigine drug co-crystal and its preparation method and use
CN103804366B (en) Lafutidine crystal compound
CN104961751B (en) A kind of Cefobutazine sodium compound and the pharmaceutical preparation containing the compound
CN106432279A (en) Method for preparing medicine ceftriaxone sodium crystal compound for treating surgical infection
CN106432278A (en) Crystalline compound of drug ceftriaxone sodium for treating surgical operation infections
CN113929629B (en) Gefitinib acid addition salts of (a)
CN111671750A (en) Co-crystal drug of levamlodipine maleate crystallized in triclinic crystal system and preparation method and application thereof
CN105985252B (en) Ornithine aspartate crystal form IV and preparation method thereof
CN104447695A (en) A kind of hydrate of benzimidazole compound
CN107868117B (en) Stanozolol saccharin salt and its preparation method and application

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant