CN102898325B - Tigecycline crystal and preparation method thereof - Google Patents
Tigecycline crystal and preparation method thereof Download PDFInfo
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Abstract
The invention relates to novel solid crystal forms of tigecycline, and comprises a method for preparing the solid crystal forms. The solid crystal forms of tigecycline provided by the invention have good stability and dissolution rate.
Description
Technical field
The invention belongs to medicinal chemistry art, relate in particular to Tigecycline crystal and preparation method thereof.
Background technology
Tigecycline (tigecycline) chemical name is (4S; 4aS; 5aR, 12aS)-4,7-two (dimethylamino)-9-[(tert-butylamino) acetamido]-3; 10; 12,12a-tetrahydroxy-1,11-dioxo-1; 4; 4a, 5,5a; 6; 11,12a-octahydro tetracene-2-methane amide is the first Glycylcycline antibiotics being approved for clinical intravenous administration; its structure is similar to tetracycline medication, and in June, 2005, U.S. FDA ratified it for infecting in be grown up complicated skin and soft tissue infection and complicated abdomen of being grown up.Tigecycline structural formula is:
Although Tigecycline and Minocycline HCl structurally have many similarities, but the former obviously will be better than traditional tetracycline medication in antimicrobial spectrum scope and resistant organism generation etc., there is broad-spectrum anti-microbial activity, be used for the treatment of the complicacy intra-abdominal infection (cIAI) and complicacy skin and skin structure infection (cSSSI) that are caused by Grain-negative or positive pathogen, anaerob and Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitivity S. aureus L-forms (MSSA).Tigecycline be a kind of newly, at treatment initial stage selective Broad spectrum antibiotics when the cause of disease not yet understands, and can not need according to impaired renal function situation adjustment dosage.
Tigecycline clinical mostly at present is amorphous tigecycline, applies in the China of PCT application application WO2006/128150, WO2007/127292 and correspondence thereof the five kinds of crystal habits (I, II, III, IV, V-type) and two kinds of solid tigecycline crystal and preparation method thereof that report Tigecycline in CN200680027182.5, CN200780014599.2 respectively.
As everyone knows, the different crystalline solid forms of same compound often have different solid state properties, such as fusing point, solvability, operability and stability, these characteristics directly can affect process and (or) the production of bulk drug and preparation, and can affect the stability of medicine, solubleness and bioavailability, so medicinal solid form directly has influence on the quality of pharmaceutical preparation, security and validity.Therefore explore a kind of dissolution rate suitable, Tigecycline crystal habit of good stability and preparation method thereof is current problem demanding prompt solution.
Summary of the invention
Goal of the invention of the present invention finds a kind of dissolution rate suitable, the Tigecycline solid crystal form of good stability and the preparation method of these crystal formations, thus pharmaceutical formulation of tigecycline quality, security, validity are improved.
In order to realize foregoing invention object, the present invention discloses a kind of crystal A of Tigecycline, and the powder x-ray diffraction of this crystal comprises 2 θ at one or more characteristic diffraction peaks of 8.4 °, 13.1 °, 16.9 °, 19.7 °, 22.6 °.
The preparation method of the Tigecycline crystal A of its correspondence is cooled by Tigecycline solution and obtains, the solvent of described Tigecycline solution is dimethyl sulfoxide (DMSO) (DMSO), N, any one in dinethylformamide (DMF), N,N-dimethylacetamide (DMA).
Or the solvent of described Tigecycline solution can replace with the one in water-tetrahydrofuran (THF) mixed solvent or water-Isosorbide-5-Nitrae-dioxane mixed solvent.
According to above-mentioned solvent requirement, the preparation method of Tigecycline crystal A specifically comprises the following steps: Tigecycline solution prepared by the solvent first adding 5 ~ 40 milliliters according to every gram of amorphous tigecycline, and this solution is stirred more than 3 hours below 40 DEG C, cooling, crystallization, filter, by crystal 40 DEG C of reduced vacuum dryings 12 ~ 24 hours.Wherein further preferably Tigecycline solution stirring more than 6 hours, more preferred churning time is 12 ~ 24 hours.Certainly the crystallization environmental optimization as Tigecycline solution is room temperature or lower temperature.
The invention also discloses the crystal B of another Tigecycline, the powder x-ray diffraction of this crystal comprises the one or more characteristic diffraction peaks of 2 θ 9.0 °, 13.9 ° and 15.4 ° simultaneously.
The preparation method of the Tigecycline crystal B of its correspondence is cooled by Tigecycline solution and obtains, and the solvent of described Tigecycline solution is any one in propylene glycol, 2-butanols, the trimethyl carbinol, Pentyl alcohol.
Or the solvent of described Tigecycline solution is the one in methylene dichloride-2-butanols mixed solvent or tetrahydrofuran (THF)-mixed with propylene glycol solvent.
According to above-mentioned solvent requirement, the preparation method of Tigecycline crystal B specifically comprises the following steps: Tigecycline solution prepared by the solvent first adding 10 ~ 30 milliliters according to every gram of amorphous tigecycline, and this solution is stirred more than 3 hours below 30 DEG C, cooling, crystallization, filter, by crystal 40 DEG C of reduced vacuum dryings 12 ~ 24 hours.Wherein further preferably Tigecycline solution stirring more than 6 hours, more preferred churning time is 12 ~ 24 hours.Certainly the crystallization environmental optimization as Tigecycline solution is room temperature or lower temperature.
Tigecycline crystal A and B the present invention prepared carries out X-ray powder diffraction, and adopt Swiss X'TRA type X-ray diffractometer, condition determination is copper target, tube voltage 40 kV, tube current 40mA, sweep velocity 12.00 °/min, sweep limit 5.00 ~ 45.00 °, step-length 0.02 °.
The X-ray powder diffraction figure of Tigecycline crystal A is shown in Fig. 1;
The X-ray powder diffraction figure of Tigecycline crystal B is shown in Fig. 2;
Its concrete grating spectrum feature, as following table:
Table 1: the X-ray powder diffraction data of Tigecycline crystal A and Tigecycline crystal B
In order to investigate the solubleness of Tigecycline crystal A provided by the invention, Tigecycline crystal B, dissolution rate and stability further, the present invention has carried out the simultaneous test of dissolution rate, steady dissolution and accelerated test to Tigecycline crystal A, Tigecycline crystal B and Tigecycline amorphous powder, and adopts high-efficient liquid phase technique (HPLC) to measure experimental result.
In the present invention, the condition of involved Syrups by HPLC is:
Chromatographic column: octadecylsilane chemically bonded silica post;
Moving phase: mobile phase A is the solution obtained by following method, is dissolved in 4.35g dipotassium hydrogen phosphate and 0.93g disodium ethylene diamine tetraacetate in 950ml water, adds triethylamine 5ml, is after 6.4, adds acetonitrile 50ml by phosphoric acid adjust ph, and mixing is filtered.
Type of elution: gradient elution.
Flow velocity:
Column temperature:
Determined wavelength: 248nm
One, test substance preparation, its preparation method is as shown in the table:
Table 2: the preparation of three kinds of Tigecycline solid form
Two, solubleness is investigated
Consider Tigecycline poor stability, easy epimerization, so in order to agree with production environment better, therefore simulation preparation dosing processing conditions, under 2-8 DEG C of condition, investigate the dissolution rate of Tigecycline in purified water and the stability in this dissolution process, experimental result is as shown in table 3:
Table 3: the dissolution rate of three kinds of Tigecycline solid form and steady dissolution experiment
| Project form | Tigecycline crystal A | Tigecycline crystal B | Tigecycline amorphous powder |
| Solid material (mg) | 500 | 500 | 500 |
| Purified water (ml) | 25 | 25 | 25 |
| Dissolution time (min) | 14 | 9 | 15 |
| HPLC detects (before dissolving bulk drug) | 99.89%, epimer 0.06%, other maximum lists assorted 0.03% | 99.91%, epimer 0.05%, other maximum lists assorted 0.03% | 99.85%, epimer 0.07%, other maximum lists assorted 0.06% |
| HPLC detects (after dissolving solution) | 99.80%, epimer 0.08%, other maximum lists assorted 0.09% | 99.88%, epimer 0.11%, other maximum lists assorted 0.05% | 99.28%, epimer 0.28%, other maximum lists assorted 0.18% |
Three, study on the stability
Adopt conventional Acceleration study to detect Tigecycline crystal A, Tigecycline crystal B and Tigecycline amorphous powder, experimental result sees the following form:
Table 4: the stability result (30 DEG C of RH65%) of the accelerated test of three kinds of Tigecycline solid form
Shown by above-mentioned experimental result, the Tigecycline crystal A in the present invention, Tigecycline crystal B solubleness under the process for processing condition of 2-8 DEG C is all greater than 20mg/ml; Simultaneously two kinds of new Tigecycline crystal solvent rate in laboratory simulation preparation freeze-drying dosing process are better, and its Acceleration study shows the good stability at two new crystal, in Acceleration study, single mixing does not have considerable change, and C-4 epimer does not change substantially.
Therefore, two kinds of new Tigecycline crystal disclosed by the invention have good solubleness, suitable dissolution rate and and stability preferably, it is steady quality in medicine processing and manufacturing process, be easy to processing, that a kind of dissolution rate is suitable, the Tigecycline solid crystal form of good stability, the pharmaceutical formulation of tigecycline quality prepared by it is good, security is high, validity is good.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction pattern of Tigecycline A crystal formation of the present invention.
Fig. 2 is the X-ray powder diffraction pattern of Tigecycline B crystal form of the present invention.
Embodiment
The present invention is further illustrated below by embodiment.Should correct understanding: the method in embodiments of the invention is only used to better explain and illustrate technical scheme of the present invention, instead of limitation of the present invention.
The preparation of embodiment 1 Tigecycline crystal A
Tigecycline amorphous powder 2g joins in 100ml there-necked flask, adds DMF (DMF) 25ml, starts and stirs, and mixture stirs 3h in 40 DEG C, is cooled to 0 ~ 5 DEG C, and filter, solid, in 40 DEG C of drying under reduced pressure 24h, obtains Tigecycline crystal A.Detect through X-ray powder diffraction, as shown in Figure 1, it has the X-ray powder diffraction characteristic peak at 2 θ angles of 8.4 °, 13.1 °, 16.9 °, 19.7 ° and 22.6+0.2 °.
The preparation of embodiment 2 Tigecycline crystal A
The amorphous 5g of Tigecycline joins in 250ml there-necked flask, add dimethyl sulfoxide (DMSO) (DMSO) 50ml, start and stir, mixture stirs 6h in 25 DEG C, be cooled to 0 ~ 5 DEG C, filter, solid is in 40 DEG C of drying under reduced pressure 24h, obtain Tigecycline, detect the crystal formation confirming as Tigecycline crystal A through X-ray powder diffraction.
The preparation of embodiment 3 Tigecycline crystal A
Tigecycline amorphous powder 3g joins in 250ml there-necked flask, add N, N-N,N-DIMETHYLACETAMIDE (DMA) 20ml, start and stir, mixture stirs 12h in 10 DEG C, is cooled to 0 ~ 5 DEG C, filter, solid, in 40 DEG C of drying under reduced pressure 24h, obtains Tigecycline, detects confirm as A crystal formation Tigecycline through X-ray powder diffraction.
The preparation of embodiment 4 Tigecycline crystal A
Tigecycline amorphous powder 4g joins in 250ml there-necked flask, add purified water 40ml, tetrahydrofuran (THF) (THF) 40ml, starts and stirs, and mixture stirs 3h in 0 ~ 5 DEG C, filter, solid, in 40 DEG C of drying under reduced pressure 24h, obtains Tigecycline crystal, detects through X-ray powder diffraction, the crystal formation characteristic peak of its characteristic peak and Tigecycline crystal A coincide, and confirms as Tigecycline crystal A.
The preparation of embodiment 5 Tigecycline crystal B
Tigecycline amorphous powder 3g joins in 100ml there-necked flask, adds 2-butanols 55ml, starts and stirs, and mixture stirs 6h in 20 DEG C, is cooled to 0 ~ 5 DEG C, and filter, solid, in 40 DEG C of drying under reduced pressure 24h, obtains Tigecycline.Detect through X-ray powder diffraction, as shown in Figure 2, there is the X-ray powder diffraction characteristic peak at the 2 θ angles of 9.0 °, 13.9 °, 15.4 °.
The preparation of embodiment 6 Tigecycline crystal B
Tigecycline amorphous powder 8g joins in 500ml there-necked flask, add methylene dichloride 160ml, 2-butanols 80ml, start and stir, mixture stirs 3h in 15 DEG C, is cooled to 0 ~ 5 DEG C, filter, solid, in 40 DEG C of drying under reduced pressure 24h, obtains Tigecycline, detects confirm as B crystal form Tigecycline through X-ray powder diffraction.
The preparation of embodiment 7 Tigecycline crystal B
Tigecycline amorphous powder 4g joins in 500ml there-necked flask, add isopropylcarbinol 100ml, start and stir, mixture stirs 12h in 10 DEG C, be cooled to 0 ~ 5 DEG C, filter, solid is in 40 DEG C of drying under reduced pressure 24h, obtain Tigecycline, detect the crystal formation confirming as Tigecycline crystal B through X-ray powder diffraction.
The preparation of embodiment 8 Tigecycline crystal B
Tigecycline amorphous powder 10g joins in 500ml there-necked flask, adds Pentyl alcohol 300ml, starts and stirs, mixture stirs 24h in 0 ~ 5 DEG C, and filter, solid is in 40 DEG C of drying under reduced pressure 24h, obtain Tigecycline, detect the crystal formation confirming as Tigecycline crystal B through X-ray powder diffraction.
The preparation of embodiment 9 Tigecycline crystal B
Tigecycline amorphous powder 3g joins in 250ml there-necked flask, add methylene dichloride 30ml, 2-butanols 30ml, starts and stirs, and mixture stirs 3h in 0 ~ 5 DEG C, filter, solid, in 40 DEG C of drying under reduced pressure 24h, obtains Tigecycline crystal, detects through X-ray powder diffraction, the crystal formation characteristic peak of its characteristic peak and Tigecycline crystal B coincide, and confirms as Tigecycline crystal B.
The preparation of embodiment 10 Tigecycline crystal B
Tigecycline amorphous powder 5g joins in 250ml there-necked flask, add tetrahydrofuran (THF) 40ml, propylene glycol 20ml, starts and stirs, and mixture stirs 3h in 0 ~ 5 DEG C, filter, solid, in 40 DEG C of drying under reduced pressure 24h, obtains Tigecycline crystal, detects through X-ray powder diffraction, the crystal formation characteristic peak of its characteristic peak and Tigecycline crystal B coincide, and confirms as Tigecycline crystal B.
Claims (8)
1. a crystal A for Tigecycline, is characterized in that the powder x-ray diffraction of this crystal comprises 2 θ at the characteristic diffraction peak of 5.200 °, 7.500 °, 8.440 °, 9.160 °, 11.200 °, 13.080 °, 13.860 °, 14.680 °, 15.240 °, 16.060 °, 16.400 °, 16.940 °, 17.660 °, 18.680 °, 18.960 °, 19.680 °, 20.280 °, 20.760 °, 21.320 °, 21.840 °, 22.560 °, 23.680 °, 24.120 °, 25.720 °, 26.600 °, 28.060 °.
2. prepare the method for Tigecycline crystal A as claimed in claim 1 for one kind, it is characterized in that described preparation method comprises the following steps: Tigecycline solution prepared by the solvent first adding 5 ~ 40 milliliters according to every gram of amorphous tigecycline, and this solution is stirred more than 3 hours below 40 DEG C, cooling, crystallization, filter, by crystal 40 ± 5 DEG C of reduced vacuum dryings 12 ~ 24 hours; The solvent of described Tigecycline solution is any one in dimethyl sulfoxide (DMSO) (DMSO), DMF (DMF), N,N-dimethylacetamide (DMA); Or the solvent of described Tigecycline solution is water-tetrahydrofuran (THF) mixed solvent.
3. the preparation method of Tigecycline crystal A as claimed in claim 2, is characterized in that described Tigecycline solution stirring more than 6 hours.
4. the preparation method of Tigecycline crystal A as claimed in claim 2, is characterized in that the described Tigecycline solution stirring time is 12 ~ 24 hours.
5. a crystal B for Tigecycline, is characterized in that the powder x-ray diffraction of this crystal comprises 2 θ at the characteristic diffraction peak of 8.260 °, 9.040 °, 10.420 °, 11.360 °, 13.140 °, 13.920 °, 15.380 °, 16.620 °, 17.940 °, 19.240 °, 19.620 °, 21.040 °, 22.800 °, 23.240 °, 24.300 °, 25.320 °, 28.840 °, 35.060 °, 35.780 °, 38.860 °, 40.220 °.
6. prepare the method for Tigecycline crystal B as claimed in claim 5 for one kind, it is characterized in that described preparation method comprises the following steps: Tigecycline solution prepared by the solvent first adding 10 ~ 30 milliliters according to every gram of amorphous tigecycline, and this solution is stirred more than 3 hours below 30 DEG C, cooling, crystallization, filter, by crystal 40 DEG C of reduced vacuum dryings 12 ~ 24 hours; The solvent of described Tigecycline solution is any one in 2-butanols, Pentyl alcohol; Or the solvent of described Tigecycline solution is the one in methylene dichloride-2-butanols mixed solvent or tetrahydrofuran (THF)-mixed with propylene glycol solvent.
7. the preparation method of Tigecycline crystal B as claimed in claim 6, is characterized in that described Tigecycline solution stirring more than 6 hours.
8. the preparation method of Tigecycline crystal B as claimed in claim 6, is characterized in that the churning time of described Tigecycline solution is 12 ~ 24 hours.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008066935A2 (en) * | 2006-11-29 | 2008-06-05 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of tigecycline and processes for preparation thereof |
| CN101228114A (en) * | 2005-05-27 | 2008-07-23 | 惠氏公司 | Methods of purifying tigecycline |
| CN101248038A (en) * | 2005-05-27 | 2008-08-20 | 惠氏公司 | Crystalline solid forms of tigecycline and methods of preparing same |
| WO2008155405A1 (en) * | 2007-06-21 | 2008-12-24 | Sandoz Ag | Crystalline solid forms |
| WO2009062964A1 (en) * | 2007-11-14 | 2009-05-22 | Sandoz Ag | Novel solvate |
| WO2009070799A1 (en) * | 2007-11-29 | 2009-06-04 | Teva Pharmaceutical Industries Ltd. | Processes for preparation of crystalline tigecycline form ii |
| CN101479235A (en) * | 2006-04-24 | 2009-07-08 | 特瓦制药工业有限公司 | Tigeycline crystalline forms and processes for preparation thereof |
| WO2009092680A2 (en) * | 2008-01-23 | 2009-07-30 | Sandoz Ag | Antibiotic compounds |
| WO2010070093A1 (en) * | 2008-12-18 | 2010-06-24 | Sandoz Ag | Crystalline form c of tigecycline dihydrochloride and methods for its preparation |
-
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- 2011-07-29 CN CN201110215760.0A patent/CN102898325B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101228114A (en) * | 2005-05-27 | 2008-07-23 | 惠氏公司 | Methods of purifying tigecycline |
| CN101248038A (en) * | 2005-05-27 | 2008-08-20 | 惠氏公司 | Crystalline solid forms of tigecycline and methods of preparing same |
| CN101479235A (en) * | 2006-04-24 | 2009-07-08 | 特瓦制药工业有限公司 | Tigeycline crystalline forms and processes for preparation thereof |
| WO2008066935A2 (en) * | 2006-11-29 | 2008-06-05 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of tigecycline and processes for preparation thereof |
| WO2008155405A1 (en) * | 2007-06-21 | 2008-12-24 | Sandoz Ag | Crystalline solid forms |
| WO2009062964A1 (en) * | 2007-11-14 | 2009-05-22 | Sandoz Ag | Novel solvate |
| WO2009070799A1 (en) * | 2007-11-29 | 2009-06-04 | Teva Pharmaceutical Industries Ltd. | Processes for preparation of crystalline tigecycline form ii |
| WO2009092680A2 (en) * | 2008-01-23 | 2009-07-30 | Sandoz Ag | Antibiotic compounds |
| WO2010070093A1 (en) * | 2008-12-18 | 2010-06-24 | Sandoz Ag | Crystalline form c of tigecycline dihydrochloride and methods for its preparation |
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Address after: 211112 Jiangsu Province, Nanjing City, Jiangning Science Park Road No. 699 Patentee after: Jiangsu Aosaikang Pharmaceutical Co., Ltd. Address before: 211112 Jiangsu Province, Nanjing City, Jiangning Science Park Road No. 699 Patentee before: Jiangsu Aosaikang Pharmaceutical Co., Ltd. |