CN102349916B - Ceforanide C-type crystal composition used for injection and its preparation method - Google Patents
Ceforanide C-type crystal composition used for injection and its preparation method Download PDFInfo
- Publication number
- CN102349916B CN102349916B CN2011102265361A CN201110226536A CN102349916B CN 102349916 B CN102349916 B CN 102349916B CN 2011102265361 A CN2011102265361 A CN 2011102265361A CN 201110226536 A CN201110226536 A CN 201110226536A CN 102349916 B CN102349916 B CN 102349916B
- Authority
- CN
- China
- Prior art keywords
- ceforanide
- type
- crystallization
- crystal
- type crystal
- 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.)
- Expired - Fee Related
Links
- DEVGLXLLDMLGJP-YFUNKXTKSA-N CC([C@H](C([C@H]1C2C3CC3)SC3)N1C2=O)C3S Chemical compound CC([C@H](C([C@H]1C2C3CC3)SC3)N1C2=O)C3S DEVGLXLLDMLGJP-YFUNKXTKSA-N 0.000 description 1
Images
Landscapes
- Cephalosporin Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a ceforanide C-type crystal composition used for injection and its preparation method, and discloses a crystal preparation method for high-purity ceforanide hydrochloride A-type crystal, namely (6R,7R)-3-[[[1-(carboxymethyl-1H-tetrazole-5-group] sulfur] methyl butyl-7-[[[2-(aminomethyl)-phenyl]2 acyl] amino]8-oxo-5-thia-1-azabicyclo[4,2,0] octyl-2-vinyl-formic acid and L-lysine B-type crystal respectively, crystal morphology parameters of the ceforanide A-type crystal and the L-lysine B-type crystal, and morphology parameters and medicinal application of ceforanide C-type crystal of sterile mixed powder consisting of the ceforanide A-type crystal and the L-lysine B-type crystal for injection for the first time.
Description
Technical field
Ceforanide for inj is one and known is widely used in clinical antibiotic, the invention belongs to and find a kind of new crystal habit in its preparation field.And this crystal habit is not yet found and disclosed, and is consistent with the clinical practice curative effect after this form is with the water for injection dissolving.
Background technology
Ceforanide (Ceforanide molecular formula C20H21N7O6S2 molecular weight 519.56 CAS registration numbers [60925-61-3]), this ingredient 1B is ceforanide for inj (the Ceforanide for Injection different name Radacef that cosolvent forms, trade name Precef, change BL-S786), real is the mixed-powder of ceforanide and two kinds of aseptic former powder of 1B, it is Mei-Mai Rui-Shi Guibao company (Bristol-Myers-Squibb is called for short BMS) research and development during by the U.S. hundred, goes on the market in the U.S. in 1984.
In the open source literature of at present relevant ceforanide preparation method and product form, there is the too complicated problem of preparation technology, perhaps the product ceforanide is amorphous form, in the aqueous solution of neutral organic solvent (50% v/v methanol/water or acetone/water) such as US4448959, add the p-methyl benzenesulfonic acid hydrate, with PH to 2.4 gained of ammonia regulator solution, need to consume a large amount of acetone and dissolve ceforanide salt (embodiment 1); Be recited as the pure ceforanide of precipitation such as WO2008/010043A embodiment 1 and embodiment 6, be the powder amorphous state, and not mentioned its concrete purity.
Yet with regard to chemical field, solid-state in the three-state of material (solid-state, liquid state and gaseous state) has various ways: crystal habit, amorphous (precipitation) form and meta form.Even especially the same medicine chemical constitution of drug world identical and because its different solid forms cause having remarkable difference at aspects such as outward appearance, dissolubility, fusing point, dissolution, biological effectiveness, purity, thereby affected stability, bioavailability and the curative effect of medicine, affected safety and the quality controllability of medicine.
" crystal formation medicine " (chief editor such as Lv Yang, the People's Health Publisher publishes) introduction in mention also that " crystal formation medicine (polymorphie drugs) is the drug products of being made by the material of advantage drug crystal forms state, namely refers to have the chemicals raw material of multiple crystal formation solid matter state.Through to the systematic study of multiple crystal-form substances, find to possess the crystalline solid of the medicinal feature of advantage, and the Solid-state Chemistry medicine of developing with advantage drug crystal forms material.The polymorphism of material is the natural phenomena that material exists, under the different conditions or in different material processing or preparation process, material can show as different crystal formation states.The polymorphism that has the Solid-state Chemistry medicine.Because the different crystal forms state of Solid-state Chemistry medicine can cause the various physical and chemical properties changes of medicine self, cause that the quality of medicine changes, can cause the difference between the effects of medicine in clinical disease treatment simultaneously.Therefore, the crystal formation state research of the Solid-state Chemistry medicine being carried out system just seems very important." just because of this, put down in writing the crystallinity inspection technique in 2010 editions two appendix of Chinese Pharmacopoeia.
In the patent aspect medicine, existing application and mandate to the crystal formation patent, such as the patent of rifampicin different crystal forms, the different crystal forms patent of adefovirdipivoxil, the mandate of the cefozopran crystal formation patent that apply at home in Japanese military field.Even to this day, yet there are no the relevant report of the crystal habit that closes ceforanide and ceforanide for inj, therefore select appropriate preparation technology, the crystal formation medicine of gaining the upper hand just seems especially important.
Summary of the invention
In order to remedy the single defective of existing ceforanide for inj form, this patent provides a kind of ceforanide and the new crystal formation form of ceforanide for inj, and this patent is the extension patent at the number of patent application 200910223572.5 of having accepted.
It is the Ceforanide C-type crystal composition for injection that the ceforanide A type crystallization for preparing in 200910223572.5 patents, the crystallization of 1B Type B and they form by application number that purpose of the present invention is intended to protect a kind of.To the preparation method of 1B Type B crystallization, namely water-organic solvent method for crystallising is protected in addition.
Described Ceforanide C-type crystal composition for injection is characterized in that: be comprised of ceforanide A type crystallization and the crystallization of 1B Type B, wherein the crystallization of 1B Type B is cosolvent.
Wherein said ceforanide A type crystallization and 1B Type B crystallized mixed mol ratio are 1:1 ~ 1:1.2.
Wherein said crystal habit refers to adopt the Cu-Ka radiation, to spend the X-ray powder diffraction spectrogram of 2 θ statement;
The crystallization of ceforanide A type exists: 4.3 ± 0.1 and/or 8.7 ± 0.1 and/or 11.6 ± 0.1 and/or 13.1 ± 0.1 and/or 15.2 ± 0.1 and/or 15.9 ± 0.1 and/or 18.5 ± 0.1 and/or 19.7 ± 0.1 and/or 21.4 ± 0.1 and/or 22.0 ± 0.1 and/or 23.4 ± 0.1 and/or 24.1 ± 0.1 and/or 25.2 ± 0.1 and/or 25.6 ± 0.1 and/or 26.9 ± 0.1 have the diffraction spectrum peak of crystal habit;
The crystallization of 1B Type B exists: 5.1 ± 0.1 and/or 10.1 ± 0.1 and/or 15.2 ± 0.1 and/or 18.6 ± 0.1 and/or 19.6 ± 0.1 and/or 20.5 ± 0.1 and/or 21.0 ± 0.1 and/or 23.6 ± 0.1 and/or 25.6 ± 0.1 and/or 30.8 ± 0.1 have the diffraction spectrum peak of crystal habit;
Ceforanide C-type crystal composition for injection exists: 4.3 ± 0.1 and/or 5.0 ± 0.1 and/or 8.7 ± 0.1 and/or 10.1 ± 0.1 and/or 11.6 ± 0.1 and/or 13.1 ± 0.1 and/or 15.2 ± 0.1 and/or 15.9 ± 0.1 and/or 18.5 ± 0.1 and/or 19.7 ± 0.1 and/or 20.3 ± 0.1 and/or 21.4 ± 0.1 and/or 22.0 ± 0.1 and/or 23.4 ± 0.1 and/or 24.1 ± 0.1 and/or 25.2 ± 0.1 and/or 25.6 ± 0.1 and/or 30.8 ± 0.1 have the diffraction spectrum peak of crystal habit.
The crystallization of wherein said ceforanide A type is analyzed among the DTA fusing point (m, p) at 223.8 ℃ ~ 235.7 ℃ in heat.
Wherein said Ceforanide C-type crystal composition for injection is used for the caused treatment that catches of antibacterial.
A kind of preparation method of Ceforanide C-type crystal composition for injection:
The preparation of step 1, the crystallization of ceforanide A type:
With ceforanide N, N-dimethylbenzyl amine salt places in the three-necked bottle, adds deionized water by w/v=1:5, stirring and dissolving, and water-bath (30 ℃) insulation behind most of dissolution of solid, adds inorganic base and stirs vacuum drawn CO
2Gas makes it reach fully dissolving, surveys the solution pH value, and transfers solution to PH=7.5 ± 0.2 with 2N hydrochloric acid; Then with the decolouring of activated carbon vacuum suction, solution respectively via hole diameter is the water solublity membrane filtration of 0.45 μ m, 0.22 μ m, uses the deionized water washed twice, and washing liquid is merged, and gets crystal solution;
In clean area, transfer the pH value isoelectric point crystallizing with 2N hydrochloric acid, namely transfer about crystal solution PH=4.0 with 2N hydrochloric acid first to make the little muddiness of solution, 25 ℃ of water bath heat preservations slowly stir ageing, nucleus is fully formed, after 30 minutes, after crystallization is separated out in a large number, lower in stirring again, slowly drip 2N hydrochloric acid, make crystal solution pH value slow decreasing, until till during PH=2.5, stop to add 2N hydrochloric acid; After this, the crystal solution pH value can slowly rise, until the crystal solution pH value stops to rise, after ten minutes, use again 2N hydrochloric acid, transfer crystal solution PH=2.0-2.5, the frozen water cooling, the crystal solution temperature is incubated 2 hours between 0 ℃-5 ℃, continue ageing, filter, with 5 ℃ of deionized water washings, drain, in 30 ℃ of following room temperatures, vacuum drying 2 hours, under 45 ℃ of vacuum dry 4 hours again, get the crystallization of ceforanide A type;
The preparation of step 2, the crystallization of 1B Type B:
1B (alkali) with drying is dissolved in the deionized water, adds active carbon, decolour in stirring at room, destaining solution respectively via hole diameter is the filter membrane aseptic filtration of 0.45 μ m, 0.22 μ m, with deionized water filter wash and merge diafiltration liquid at twice, places constant pressure funnel for subsequent use;
With charcoal treatment, aseptic filtration, under the isopropyl alcohol that filters places and seals in the three-necked bottle, the speed of above-mentioned 1B solution with 40 of per minutes is splashed in the isopropyl alcohol, after dropwising, make its precipitation turn brilliant in stirring at room, when this process is used polarized light microscope observing, as seen product is solution state to non-hygroscopic from moisture absorption under microscopy, and observe crystalline solid, and rotate at 360 degree object stages simultaneously, have till birefringence and the extinction position phenomenon, last more than 2 hours, this process shows that product changes into crystal type from indefiniteness; Be cooled to below-5 ℃ 2 hours with brine ice again, filter, isopropyl alcohol wash twice, room temperature vacuum drying 2 hours, 55 ℃ of vacuum dryings 4 hours get the crystallization of 1B Type B;
The preparation of step 3, Ceforanide C-type crystal composition for injection:
The ceforanide A type crystallization and the crystallization of 1B Type B that obtain in step 1, the step 2 are pulverized with pulverizer respectively, cross the 180-200 mesh sieve, for subsequent use; Press the crystallization of ceforanide A type and mix with 1B Type B crystallization mol ratio 1:1 ~ 1:1.2, after in the mixed powder machine of three-dimensional powder, fully mixing, namely get end product.
Wherein the crystallization of 1B Type B be with the 1B aqueous solution after aseptic filtration, crystallization in lower alcohol and rudimentary ether.
Wherein lower alcohol can be selected n-butyl alcohol, isobutanol, butyl alcohol-tert, isooctanol; Rudimentary ether is selected petroleum ether, ether, diisopropyl ether.
The technique effect that the present invention brings is: 1) than the amorphous ceforanide of published precipitation, ceforanide A type of the present invention crystallization is a kind of new typing crystal habit, adopt the isoelectric point crystallizing method to make, has non-hygroscopic stable physical characteristic, purity is high, its HPLC purity〉99.16%; 2) preparation technology of ceforanide A type crystallization is simple, easy to operate, saves time; 3) the present invention is when the preparation Ceforanide C-type crystal composition for injection, and the solvent of selecting is water and dilute hydrochloric acid, without the use of poisonous and harmful substance, and more environmental protection, low-carbon (LC), basic non-environmental-pollution more is conducive to the protection of natural environment.
Description of drawings
Fig. 1-the 1st, the HPLC figure of ceforanide A type crystallization;
Fig. 1-2 is the gentle HPLC figure of putting 24 months of ceforanide A type crystallisation chamber;
Fig. 1-the 3rd uses Na
2CO
3Replace NaHCO
3Make the HPLC figure of ceforanide A type crystallization;
Fig. 2 is ceforanide A type crystallization X-ray powder diffraction pattern;
Fig. 3 is 1B Type B crystallization X-ray powder diffraction pattern;
Fig. 4 is Ceforanide C-type crystal composition for injection X-ray powder diffraction pattern;
Fig. 5 is the crystallization of ceforanide A type, the crystallization of 1B Type B, Ceforanide C-type crystal composition for injection, the X-ray powder diffraction stacking chart of three kinds of crystallizations;
Fig. 6 is the DTA thermal analysis curue of ceforanide A type crystallization;
Wherein: above-mentioned HPLC collection of illustrative plates test condition is as follows:
Instrument model: LD-20, Japanese Shimadzu
C
18Post (Diamonsil) 5 μ m, 250mm * 4.6mm,
λ (detection wavelength) 254nm,
Flow velocity φ 1ml/min,
Mobile phase: 0.1mol, KH
2PO
4: methanol=85:15;
Above-mentioned X-ray powder diffraction pattern test condition:
Instrument model: (China, Dandong, circumference Instr Ltd.) DX-2600, Cu-target, power 40KV * 30mA
Scanning θ-2 θ of stepping graphite single speed,
Slit: 1 °, 1 °, 0.2mm.
The specific embodiment
Below in conjunction with examples of implementation the present invention is further described in detail, but be not limitation of the invention, all technology that realizes based on foregoing of the present invention all belong to the scope of the invention.
1, the preparation of Ceforanide C-type crystal composition for injection
Embodiment 1: the preparation of ceforanide A type crystallization:
Press embodiment 9 resulting ceforanide N in the number of patent application 200910223572.5, N-dimethylbenzyl amine salt (CRD-HDMBA) chemical compound [2] 65.48g, place in 1000 milliliters of three-necked bottles, add 328ml deionized water (w/v=1:5), stirring makes its dissolving, with water-bath (30 ℃) insulation, behind most of dissolution of solid, add 3.0g NaHCO
3Stir vacuum drawn CO
2Gas makes it reach fully dissolving, survey the solution pH value, and a little transfers solution to PH=7.5 ± 0.2 with 2N hydrochloric acid.Then with the decolouring of activated carbon 6.5g vacuum suction, solution respectively via hole diameter is the water solublity membrane filtration of 0.45 μ m, 0.22 μ m, washs at twice with the 100ml deionized water again, and washing liquid is merged, and gets crystal solution; In clean area, transfer the pH value isoelectric point crystallizing with 2N hydrochloric acid, namely transfer about crystal solution PH=4.0 with 2N hydrochloric acid first to make the little muddiness of solution, 25 ℃ of water bath heat preservations slowly stir ageing, nucleus is fully formed, after 30 minutes, after crystallization is separated out in a large number, lower in stirring again, slowly drip 2N hydrochloric acid, make crystal solution pH value slow decreasing, until till during PH=2.5, stop to add 2N hydrochloric acid; After this, the crystal solution pH value can slowly rise, until the crystal solution pH value stops rising, after ten minutes, use again 2N hydrochloric acid a little, transfer crystal solution PH=2.0-2.5, the frozen water cooling, the crystal solution temperature is between 0 ℃-5 ℃, be incubated 2 hours, continue ageing, filter, with 5 ℃ of deionized water 100ml washings, drain, in 30 ℃ of following room temperatures, vacuum drying 2 hours, under 45 ℃ of vacuum dry 4 hours again, get ceforanide A type crystallization 48.25g, weight rate 73.69%, mole rate 92.87%, finished product HPLC purity is 99.16%.See Fig. 1-1.Chemical compound [1] ceforanide structural formula:
Chemical compound [2] ceforanide-dimethylbenzyl amine salt structural formula:
The preparation of embodiment 2:L-lysine Type B crystallization:
With commercially available spray-dired 1B (alkali) 25.0g, be dissolved in the 125ml deionized water, add active carbon 5.0g, in stirring at room decolouring in 60 minutes, destaining solution respectively via hole diameter is the filter membrane aseptic filtration of 0.45 μ m, 0.22 μ m, with 25ml deionized water filter wash and merge diafiltration liquid at twice, place constant pressure funnel for subsequent use.
With charcoal treatment, aseptic filtration, under the isopropyl alcohol 3000ml that filters places and seals in the 1 liter three-necked bottle, with the speed of above-mentioned 1B solution with 40 of per minutes, constant speed splashes in the isopropyl alcohol, after dropwising, make its precipitation turn brilliant in stirring at room, when this process was used polarized light microscope observing, visible product was solution state to non-hygroscopic from moisture absorption under microscopy, and observes crystalline solid, rotate at 360 degree object stages simultaneously, have till birefringence and the extinction position phenomenon, last more than 2 hours, this process shows that product changes into crystal type from indefiniteness; Be cooled to below-5 ℃ 2 hours with brine ice, filter, isopropyl alcohol 50ml * 2 wash twice, room temperature vacuum drying 2 hours, and 55 ℃ of vacuum dryings 4 hours get 1B Type B crystallization 20.2g.
In preparation, can also select lower alcohol and the petroleum ether such as n-butyl alcohol, isobutanol, butyl alcohol-tert, isooctanol, ether, the rudimentary ether such as diisopropyl ether substitutes isopropyl alcohol.
Embodiment 3: the preparation of Ceforanide C-type crystal composition for injection:
The ceforanide A type crystallization and the crystallization of 1B Type B that obtain among embodiment 1, the embodiment 2 are pulverized with pulverizer respectively, cross the 180-200 mesh sieve, for subsequent use.
Press the crystallization of ceforanide A type and mix with 1B Type B crystallization mol ratio 1:1 ~ 1:1.2, after in the mixed powder machine of three-dimensional powder, fully mixing, be sub-packed in the mould vial by every bottle of 1.3g-1.32g again, namely get object.
Above-mentioned ceforanide for inj C type crystalline mixture was deposited 24 months under 25 ℃ of room temperatures, and its HPLC purity is 99.02% on inspection, and is still unchanged.Data show that ceforanide for inj C type crystalline mixture is stable, more are conducive to clinical use, see Fig. 1-2.
With 3.0g NaHCO among the embodiment 1
3Replace with 2.0g Na
2CO
3, other steps are constant, and preparing the crystallization of ceforanide A type is 49.11g, and its HPLC purity is 99.22%, sees shown in Fig. 1-3.
The sign of the crystal habit of 2, ceforanide A type crystallization, the crystallization of 1B Type B, ceforanide C type crystal composition
A) sign of the crystal habit of ceforanide A type crystallization
Ceforanide A type crystallization sample powder is inserted blind hole solid sample holder (20mm * 18mm * 0.15mm), scrape with wave plate and to be inserted into instrument (China, Dandong, circumference Instr Ltd.) DX-2600 after the pressing, the Cu-target, power 40KV * 30mA specimen disc chooses test condition, step-scan: 2 θ are from 3 ° to 43 °, sampling time is 1 second, 0.03 ° of step-length after to be scanned the finishing, is carried out the polycrystal powder sample data and is collected.
The sign of ceforanide A type crystal habit: a) according to the crystallinity inspection technique of putting down in writing in 2010 editions two appendix of Chinese Pharmacopoeia, X-ray powder diffraction crystal characteristic parameter is as follows, and collection of illustrative plates is seen Fig. 2 (being not limited only to this):
B) its heat is analyzed the DTA test, and show that the fusing point of ceforanide A type crystallization is: (m, p) 223.8 ℃ ~ 235.7 ℃ (dec) see Fig. 6.
B) crystal habit of 1B Type B crystallization characterizes
Being characterized by of 1B Type B crystal habit: according to the crystallinity inspection technique of putting down in writing in 2010 editions two appendix of Chinese Pharmacopoeia, X-ray powder diffraction crystal characteristic parameter is as follows, and collection of illustrative plates is seen Fig. 3 (being not limited only to this).
[0030] C) sign of the crystal habit of ceforanide C type crystal composition
The sign of ceforanide C type crystal composition form: according to the crystallinity inspection technique of putting down in writing in 2010 editions two appendix of Chinese Pharmacopoeia, X-ray powder diffraction crystal characteristic parameter is as follows, collection of illustrative plates is seen Fig. 4 (being not limited only to this), and the crystalline state stacking chart of ceforanide A type crystallization and the crystallization of 1B Type B sees Fig. 5.
Claims (3)
1. Ceforanide C-type crystal composition for injection, it is characterized in that: be comprised of ceforanide A type crystallization and the crystallization of 1B Type B, wherein the crystallization of 1B Type B is cosolvent;
The form of described crystallization refers to adopt the Cu-Ka radiation, spending the X-ray powder diffraction spectrogram of 2 θ statement, the crystallization of ceforanide A type as shown in Figure 2, the crystallization of 1B Type B as shown in Figure 3, Ceforanide C-type crystal composition for injection is as shown in Figure 4.
2. Ceforanide C-type crystal composition for injection according to claim 1, the crystallization of wherein said ceforanide A type is analyzed among the DTA fusing point (m, p) at 223.8 ℃～235.7 ℃ in heat.
3. Ceforanide C-type crystal composition for injection according to claim 1, wherein said Ceforanide C-type crystal composition for injection is used for the caused treatment that catches of antibacterial.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102265361A CN102349916B (en) | 2010-08-24 | 2011-08-09 | Ceforanide C-type crystal composition used for injection and its preparation method |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010261176.4 | 2010-08-24 | ||
| CN2010102611764A CN101926804A (en) | 2010-08-24 | 2010-08-24 | Ceforanide C-type crystal composition for injection and preparation method thereof |
| CN2011102265361A CN102349916B (en) | 2010-08-24 | 2011-08-09 | Ceforanide C-type crystal composition used for injection and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102349916A CN102349916A (en) | 2012-02-15 |
| CN102349916B true CN102349916B (en) | 2013-02-20 |
Family
ID=43366409
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102611764A Pending CN101926804A (en) | 2010-08-24 | 2010-08-24 | Ceforanide C-type crystal composition for injection and preparation method thereof |
| CN2011102265361A Expired - Fee Related CN102349916B (en) | 2010-08-24 | 2011-08-09 | Ceforanide C-type crystal composition used for injection and its preparation method |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102611764A Pending CN101926804A (en) | 2010-08-24 | 2010-08-24 | Ceforanide C-type crystal composition for injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN101926804A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101926804A (en) * | 2010-08-24 | 2010-12-29 | 中国医药集团总公司四川抗菌素工业研究所 | Ceforanide C-type crystal composition for injection and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008010043A2 (en) * | 2006-07-18 | 2008-01-24 | Orchid Chemicals & Pharmaceuticals Limited | Improved process for the preparation of ceforanide in pure form |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101926804A (en) * | 2010-08-24 | 2010-12-29 | 中国医药集团总公司四川抗菌素工业研究所 | Ceforanide C-type crystal composition for injection and preparation method thereof |
-
2010
- 2010-08-24 CN CN2010102611764A patent/CN101926804A/en active Pending
-
2011
- 2011-08-09 CN CN2011102265361A patent/CN102349916B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008010043A2 (en) * | 2006-07-18 | 2008-01-24 | Orchid Chemicals & Pharmaceuticals Limited | Improved process for the preparation of ceforanide in pure form |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101926804A (en) | 2010-12-29 |
| CN102349916A (en) | 2012-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103833626B (en) | Crystal formation of chidamide and preparation method thereof and application | |
| CN101909629A (en) | Crystalline (R)-2-(4-cyclopropanesulphonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydropyran-4-yl)-propionamide | |
| CN102924483B (en) | Ceftazidime crystal compound, preparation method of compound and pharmaceutical composition of compound in sterile mixed powder form | |
| CN107921021A (en) | Crystalline compounds | |
| CN105408329A (en) | Salts of dasatinib in crystalline form | |
| CN103951562A (en) | Crystal form of chlorogenic acid and preparation method thereof | |
| CN102363617A (en) | Ertapenem monosodium salt crystal and preparation method thereof | |
| CN106083792A (en) | The dihydromyricetin hydrate crystallization of dextrorotation | |
| CN102349916B (en) | Ceforanide C-type crystal composition used for injection and its preparation method | |
| CN105246877A (en) | Novel form of pyrimidinic compound having dibenzylamine structure | |
| CN106265536B (en) | Bortezomib pharmaceutical composition and preparation method thereof | |
| CN102766097A (en) | Edaravone A-type crystal and preparation method thereof | |
| CN102942576B (en) | New crystal form composition of cefminox sodium and preparation method thereof | |
| CN102557918B (en) | Ibuprofen sodium compound and new preparation method thereof | |
| CN104530082B (en) | Cefathiamidine compound | |
| CN103025753A (en) | Crystalline ezatiostat hydrochloride ansolvate | |
| CN110372576A (en) | A kind of calcium channel blocking drug molecule eutectic and preparation method thereof | |
| CN103992219B (en) | Hydroxyl amyl group Potassium Benzoate crystal and preparation method thereof | |
| CN102584790A (en) | S-pantoprazole sodium trihydrate, and preparation method and application thereof | |
| CN105566316A (en) | Dibenzo quinolizine compound entity and application thereof | |
| CN102659644B (en) | Crystal forms of 2-aminoethyl sulfonic acid and preparation processes for crystal forms | |
| CN103130661A (en) | Crystal and amorphous substance of dapoxetine hydrochloride and preparation method thereof | |
| Runčevski et al. | On the hydrates of codeine phosphate: the remarkable influence of hydrogen bonding on the crystal size | |
| CN102846561A (en) | Ozagrel sodium drug combination for injection | |
| CN101607968A (en) | Vinflunine salt, its preparation method and pharmaceutical composition thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130220 Termination date: 20210809 |